B
Data Tables
Note: Abbreviations/acronyms included in the following data tables are included in the Glossary (see Appendix A).
Studies on Women, Infants, and Children
TABLE B-1a Studies on Preeclampsia: Effects on Women Who Increase Seafood and/or Omega-3 Fatty Acid Intake
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Sibai, 1998 |
Review |
3 randomized controlled trials |
Fish-oil supplement |
|
|
Sindelar et al., 2004 |
Randomized Controlled Trial |
Men (n=8) Women (n=4) Mean age of 33 years Lincoln, NE Non-Hispanic White Recruited at YMCA marathon and triathlon training group meetings and word of mouth Exercising regularly as members of a running training group sponsored by the local YMCA No being treated with eating disorders or depression, or those unable to eat eggs, or those using medications known to affect serum lipids |
n-3 PUFA-enriched eggs |
2 weeks baseline period, 4 weeks treatment period (crossover design), 4 weeks washout period between treatments |
|
Haugen and Helland, 2001 |
Randomized Controlled Trial |
Pregnant women (n=37) Mean age about 27-31 years Oslo, Norway Normotensive without proteinuria, had uncomplicated term pregnancies, randomly taken from another study investigating the influence of omega-3 fatty acids on fetal, neonatal, and child development Another group had moderate preeclampsia |
Cod-liver oil supplement |
16-20 weeks gestation through pregnancy |
|
Amount |
Results |
Conclusion* |
|
|
“The beneficial effects of fish oil on the incidence of preeclampsia are supported by observational studies and 1 large, uncontrolled early trial.” Three randomized trials “reveal no reduction in the incidence of preeclampsia in the fish oil group.” |
N |
|
n-3 PUFA-enriched eggs: flaxseed added to hens’ diet 350 mg n-3 PUFA/60 g egg 0.25 g LA, 0.10 g DHA/60 g egg 1 egg/day for 6 days and no eggs on day 7 Conventional eggs: 60 mg of n-3 PUFA/60 g egg 0.04 g LA, 0.02 g DHA/60 g egg 1 egg/day for 6 days and no eggs on day 7 |
LA, DHA, and total n-3 dietary intake of those randomized to n-3 PUFA-enriched egg treatment were significantly higher than at baseline and compared to the conventional egg treatment (p<0.05). There were no significant differences in serum total cholesterol, LDL-C and HDL-C in physically active adults from baseline to end of treatment or between groups. Serum triglycerides were significantly higher with n-3 PUFA-enriched egg treatment than those from baseline and compared to the conventional egg treatment (p<0.05). |
N/A |
|
Cod-liver oil group: 10 mL/day Corn oil group: 10 mL/day |
“The pressure increase was significant in both groups, but no significant differences in the constrictory response or in the proportions of preparations displaying dilatatory responses were observed when compared to appropriate control groups.” “Neither preeclampsia nor dietary supplementation with cod-liver oil had any significant effect on the vasoactive response to PGF2α in umbilical cord arteries.” |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Salvig et al., 1996 |
Randomized Controlled Trial |
Pregnant women (n=533) Aged 18-44 years Aarhus, Denmark No history of placental abruption in an earlier pregnancy or a serious bleeding episode in the present pregnancy, no prostaglandin inhibitors regularly, no allergy to fish and regular intake of fish oil |
Fish-oil supplement |
30th week gestation through pregnancy |
|
Onwude et al., 1995 |
Randomized Controlled Trial |
Pregnant women (n=233) Aged 18-39 years for fish oil group Aged 16-40 for placebo group Leeds, UK Multigravida with a history of one or more small babies, a history of proteinuric or nonproteinuric pregnancy-induced hypertension, or a history of unexplained stillbirth Primigravida with abnormal uterine arcuate artery Doppler blood flow at 24 weeks gestation |
EPA/DHA supplement |
Until 38th week gestation; enrollment time unspecified |
|
Bulstra-Ramakers, 1995 |
Randomized Controlled Trial |
Pregnant women (n=63) Groningen, Netherlands Birth weight below the 10th percentile in association with pregnancy-induced hypertension or chronic renal disease, or with placenta abnormalities |
EPA supplement |
12-14 weeks gestation until delivery |
|
Amount |
Results |
Conclusion* |
|
Fish oil group: 2.7 g/day (4 capsules/day, each capsule contains 32% EPA, 23% DHA, 2 mg tocopherol/ml) Olive oil group: 1 g; 72% oleic acid and 12% LA/capsule 4 capsules/day Control = no capsule |
“Mean blood pressure increased during the course of the 3rd trimester,” but this change was not statistically different among the three groups. “No differences were seen between the groups in proportions of women with a systolic blood pressure above 140 mmHg or a systolic blood pressure above 90 mmHg, although the proportion of women with diastolic above 90 mmHg tended to be lower in the fish oil group compared to the olive oil group (RR=0.48, p=0.07).” |
N |
|
2.7 g/day (1.62 g/day of EPA) (1.08 g/day of DHA) |
There were no significant differences between the two groups for proteinuric pregnancy-induced hypertension, nonproteinuric pregnancy-induced hypertension, birth weight, gestation length, perinatal death, duration of labor, onset of labor (spontaneous, induced, or prelabor section), or mode of delivery. |
N |
|
4 capsules 3 times/day (each capsule contains 0.25 mg EPA ) vs. placebo |
“Addition of 3 g/day of EPA to the diet did not result in either a lowering of the incidence of pregnancy induced hypertension or intrauterine growth retardation.” “Birth weight centiles were slightly lower and the recurrence rate of pregnancy-induced hypertension was slightly higher in the EPA group,” compared to the control group, although these differences were not significant. |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Schiff et al., 1993 |
Controlled Trial |
Pregnant women (n=16) Aged 25-34 years Nulliparous Nonsmokers, no history of hypertension, coagulation disorders, thrombocytopenia, or chronic vascular, renal, or other disease |
Fish-oil supplement |
32-34 weeks through the next 21 days |
|
Olsen and Secher, 1990 |
Randomized Controlled Trial |
Pregnant women (n=5022) Aged 15-44 years London People’s League of Health, 1946 Attending antenatal clinics of 10 hospitals No disease or physical abnormality |
EPA/DHA supplement |
Enrolled at <24 weeks gestation; treatment lasts for <15 weeks (n=288), 16-19 weeks (n=411), 20-23 weeks (n=414), or 24+ weeks (n=417) |
|
Amount |
Results |
Conclusion* |
|
6 capsules/day (each capsule contains 1000 mg of concentrated fish oil, 26% of which is n-3 fatty acids) |
“Mean excretion of 11-dehydro-thromboxane B2 before and after 21 days of fish oil consumption was reduced among the fish oil-treated women from 1606±411 pg/mg of creatinine to 779±299 pg/mg after treatment (p<0.0001, paired t test). In all 11 patients the decreased excretion of this metabolite was considerable, ranging from 32% to 71%.” No significant change was detected among the control women. |
B |
|
0.1 g/day of EPA+DHA from halibut oil in supplement vs. no supplement Supplement includes 0.26 g ferrous iron; 0.26 g calcium; minute quantities of iodine, manganese and copper; 0.60 g thiamin/g; 0.10 g vitamin C; 0.36 g halibut liver oil |
In primiparae, the OR for preeclampsia was significant when comparing the treatment to the control group (OR=0.689, 95% CI 0.50-0.95). In primiparae, the OR for albuminuria was statistically significant when comparing the treatment to the control group (OR=0.717, 95% CI 0.54-0.96). In primiparae, the OR for hypertension was not significant when comparing the treatment to the control group (OR=0.862, 95% CI 0.73-1.02). In multiparae, these statistics were OR=0.677 (95% CI 0.43-1.07), OR=0.675 (95% CI 0.44-1.04), and OR=1.121 (95% CI 0.89-1.42). There were no significant effects on the occurrences of stillbirths, early neonatal deaths (before 8 days), perinatal deaths, sepsis, or the duration of labor. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Clausen et al., 2001 |
Cohort |
Pregnant women (n=3133) Mean age 29.8 years 51.8% nulliparous Representing all socioeconomic classes Aker University Hospital, Oslo, Norway No pregestational diabetes or twin/triplet pregnancies |
Fatty acids from food |
17-19 weeks gestation until after delivery |
|
Amount |
Results |
Conclusion* |
|
Tertiles of saturated fatty acids (%energy) Mean = ≤12.0, 12.0-15.0, >15.0 Tertiles of monounsaturated fatty acids (%energy) Mean = ≤10.5, 10.5-13.0, >13.0 Tertiles of polyunsaturated fatty acids (%energy) Mean = ≤5.2, 5.2-7.5, >7.5 Tertiles of omega-3 fatty acids (%energy) Mean = ≤0.9, 0.9-1.6, >1.6 Tertiles of omega-6 fatty acids (%energy) Mean = ≤3.8, 3.8-5.8, >5.8 |
After adjusting for energy, age, smoking, BMI, systolic blood pressure for 20 weeks’ gestation, nullipara and energy: Statistically significant ORs for preeclampsia, comparing the highest group to the lowest group of fatty acid intakes, were observed for polyunsaturated fatty acids (p=0.01) and omega-6 fatty acids (p=0.05); and Statistically nonsignificant ORs for preeclampsia, comparing the highest group to the lowest group of fatty acid intakes, were observed for saturated fat (p=0.10), monounsaturated fat (p=0.59), and omega-3 fatty acids (p=0.06). |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Velzing-Aarts et al., 1999 |
Case-control |
Cases (n=27) = preeclamptic women Controls (n=24) = normotensive, nonproteinuric women Pregnant women Mean age about 27 years Curacao |
Fatty acid composition in maternal and umbilical platelets and umbilical arteries and veins |
During delivery or within 2 hours after birth |
|
Amount |
Results |
Conclusion* |
|
Mean fatty acid composition in maternal platelets (in mol%): Controls = 9.66±2.75 LA; 0.27±0.10 ALA; 0.29±0.14 EPA; 2.03±0.62 DHA Cases = 7.0±21.91 LA; 0.22±0.11 ALA; 0.21±0.07 EPA; 2.16±0.93 DHA Mean fatty acid composition in umbilical cord platelets (in mol%): Controls = 3.73±0.76 LA; 0.14±0.10 ALA; 0.16±0.07 EPA; 2.33±0.58 DHA Cases = 4.16±1.51 LA; 0.21±0.11 ALA; 0.17±0.07 EPA; 1.97±0.30 DHA Mean fatty acid composition in umbilical veins (in mol%): Controls = 2.69±0.44 LA; 0.10±0.05 ALA; 0.09±0.04 EPA; 4.26±0.85 DHA Cases = 2.89±0.56 LA; 0.11±0.05 ALA; 0.07±0.02 EPA; 3.35±0.96 DHA Mean fatty acid composition in umbilical arteries (in mol%): Controls = 1.87±0.39 LA; 0.10±0.04 ALA; 0.09±0.03 EPA; 4.83±0.76 DHA Cases = 1.74±0.75 LA; 0.10±0.06 ALA; 0.06±0.03 EPA; 3.73±1.03 DHA |
“Newborns of preeclamptic women had significantly lower birth weights and gestational ages at delivery,” compared to newborns of non-preeclamptic women. Preeclamptic women had significantly lower maternal platelet levels of LA (p<0.001) and EPA (p<0.05) compared to normotensive women. Preeclamptic women had significantly lower umbilical arteries levels of EPA (p<0.01) and DHA (p<0.001) compared to normotensive women. No other significant differences were found for LA, ALA, EPA, or DHA. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Kesmodel et al., 1997 |
Nested case-control |
Cases = women with preeclampsia (n=43), pregnancy-induced hypertension (n=179), intrauterine growth retardation (n=182), delivering preterm (n=153), delivering postterm (n=189) Control = sample from whole cohort (n=256) Pregnant women Aarhus, Denmark |
Seafood and fish-oil supplement |
Between 6 months and 3 1/2 years after delivery |
|
Williams et al., 1995 |
Case-control |
Cases (n=22) = preeclamptic Controls (n=40) = normotensive Pregnant women Mean age 28.6-31.2 years White (n=17 in preeclamptic group, n=23 in non-preeclamptic group) Seattle, Washington About 21% Medicaid recipient |
Maternal erythrocytes fatty acid profiles |
Day after delivery |
|
Amount |
Results |
Conclusion* |
|
Low intake = Maximum of 1 fish snack/week and 1 fish meal/month and no fish oil High intake = Minimum of 4 fish snacks/week or 4 fish meals/month or intake of fish oil during pregnancy Middle intake = Everyone else |
After adjusting for maternal smoking habits, maternal height, maternal weight before pregnancy, parity, maternal social status, and average daily calcium intake: There were no significant ORs of pregnancy-induced hypertension, preeclampsia, intrauterine growth retardation, preterm delivery or postterm delivery for the middle-intake group or the high-intake group compared to the low-intake group. |
N |
|
Tertiles of EPA: Median = 0.20, 0.26, 0.36 Tertiles of DPA: Median = 1.54, 1.75, 2.02 Tertiles of DHA: Median = 4.38, 5.14, 6.40 Tertiles of total long-chain n-3 fatty acids: Median = 6.23, 7.09, 8.50 |
After adjusting for parity and pre-pregnancy BMI, the OR of preeclampsia for the lowest tertile of EPA, compared to the highest tertile of EPA was 5.54 (95% CI 1.06-28.79). After adjusting for parity and pre-pregnancy BMI, the OR of preeclampsia for the lowest tertile of DPA, compared to the highest tertile of DPA was 3.33 (95% CI 0.65-16.99). After adjusting for parity and pre-pregnancy BMI, the OR of preeclampsia for the lowest tertile of DHA, compared to the highest tertile of DHA was 7.54 (95% CI 1.23-46.22). After adjusting for parity and pre-pregnancy BMI, the OR of preeclampsia for the lowest tertile of the sum of long-chain omega-3 fatty acids, compared to the highest tertile of long-chain omega-3 fatty acids was 7.63 (95% CI 1.43-40.63). |
B |
|
Amount |
Results |
Conclusion* |
|
Nonpregnant women (mg/L±SE): 79.51±3.47 total PUFA, 60.79±2.28 LA, 10.99±1.01 AA, 1.88±0.17 ALA, 0.26±0.04 EPA, 5.58±0.60 DHA Normal pregnant women (mg/L±SE): 90.60±6.68 total PUFA, 62.93±4.69 LA, 12.81±0.87 AA, 3.68±0.99 ALA, 1.08±0.33 EPA, 10.40±0.94 DHA Preeclamptic women (mg/L±SE): 67.42±3.88 total PUFA, 45.98±2.80 LA, 11.44±1.00 AA, 1.11±0.25±ALA, 0.11±0.11 EPA, 8.94±0.69 DHA |
Plasma total polyunsaturated fatty acid levels, LA, ALA, and EPA were all significantly higher in the normal pregnant women than in the preeclamptic women (p<0.05, p<0.01, p<0.05, p<0.05, respectively). EPA and DHA were significantly lower in the nonpregnant women compared to the pregnant women (p<0.05 and p<0.01, respectively). No other significant differences between the plasma polyunsaturated fatty acid levels in the three groups were found. “No statistical differences were noted in the five polyunsaturated fatty acid levels between fasting and non-fasting states in both non-pregnant and normal pregnant subjects.” |
B |
TABLE B-1b Studies on Postpartum Depression: Effects on Women Who Increase Seafood and/or Omega-3 Fatty Acid Intake
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Marangell et al., 2004 |
Open trial |
Pregnant women (n=7) Aged 31-42 years Married, Caucasian (except for one married, Hispanic) Baylor College of Medicine History of a depressive episode in the postpartum period, not suffering from a current depressive episode No psychotropic medications within 2 weeks of baseline, history of nonreponse to two or more antidepressants, serious comorbid medical or psychiatric illness, or significant risk of dangerousness to self or others |
Fish-oil supplement |
34-36 weeks gestation until 12 weeks postpartum |
|
Llorente et al., 2003 |
Randomized Controlled Trial |
Pregnant women (n=89) Aged 18-42 years No chronic medical condition, no dietary supplements other than vitamins, no smoking, who had not been pregnant >5 times Planned to breastfeed infants exclusively for at least 4 months Part of a larger cohort study on effects of DHA on breastfeeding mothers and their infants |
Algae-derived triglyceride supplement |
Within a week of delivery to 4 months after delivery |
|
Hibbeln and Salem, 1995 |
Review |
Summary of three cohorts |
DHA depletion |
|
|
Amount |
Results |
Conclusion* |
|
Fish oil group: 2960 mg fish oil/day 173 mg EPA and 123 mg DHA per day 10 capsules/day |
Trial was terminated because of a high relapse rate observed after enrolling only seven participants. |
N |
|
Algae-derived triglyceride capsule (about 200 mg DHA/day) vs. placebo |
“Repeated measures analysis of variance, with the use of data only from the women who completed the questionnaires at both baseline and 4 months, showed no difference between the two groups at any time” with regards to postpartum depression. “There were no significant differences between groups in the EPDS and SCID-CV scores, particularly in current or past episodes of depression, as detected by the SCID-CV.” “There were no significant correlations between plasma phospholipid DHA content and BDI, EPDS, or SCID-CV scores.” |
N |
|
|
“The relative maternal depletion of DHA may be one of the complex factors leading to increased risk of depression in women of childbearing age and in postpartum periods.” |
B |
|
Amount |
Results |
Conclusion* |
|
Rare eaters: ≤1 time/month Regular eaters: ≥1 time/week Serving size unspecified |
After adjusting for body mass index, serum total cholesterol level, and socioeconomic situation, women who ate fish rarely had a higher OR for depression, compared to women who ate fish regularly. This statistic was observed by various measurements: Doctor-diagnosis: OR=1.3 (95% CI 0.9-1.9); HSCL-25 <2.01: OR=1.4 (95% CI 1.1-1.9); HSCL-25 <2.01 and doctor-diagnosis: OR=2.6 (95% CI 1.4-5.1). After adjusting for alcohol intake, smoking, physical inactivity, and marital status, women who ate fish rarely had a higher OR for depression, compared to women who ate fish regularly. This statistic was observed by various measurements: Doctor-diagnosis: OR=1.2 (95% CI 0.9-1.6); HSCL-25 <2.01: OR=1.4 (95% CI 1.1-1.8); HSCL-25 <2.01 and doctor-diagnosis: OR=2.4 (95% CI 1.4-4.2). Among men, none of these ORs were significant. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Otto et al., 2003 |
Cohort |
Participated in 2 earlier studies Pregnant women (n=112) Mean age around 30 years Caucasian Southern Limburg, Netherlands Fish intake <2 times/week No metabolic, cardiovascular, neurologic, renal, or psychiatric disorders No medications, except for multivitamins and iron supplements Singleton pregnancy Term delivery No blood transfusions in the perinatal period Gestational age <14 weeks at entry, Caucasian, fish consumption <2 times a week (for Study 2 only) |
Venous (plasma) blood fatty acid composition |
36 weeks gestation, at delivery, and 32 weeks postpartum |
|
Otto et al., 2001 |
Cohort |
Pregnant women (n=57) Mean age around 30 years Southern Limburg, Netherlands No metabolic, cardiovascular, neurologic, or renal disorders No medications, except multivitamins and iron supplements Singleton pregnancy Term delivery No blood transfusions in the perinatal period |
Diet and venous blood fatty acid profiles |
36-37 weeks gestation; 2-5 days after delivery; 1, 2, 4, 8, 16, 32, 64 weeks postpartum |
|
Amount |
Results |
Conclusion* |
|
Absolute amount not specified |
No significant relationship was observed between DHA, n-6DPA, or their ratio and the EPDS scores at delivery or at 32 weeks postpartum. No statistically significant relationships between depression and fatty acid status were observed with DHA or n-6DPA, neither for the levels at delivery, nor for their postpartum changes. “The improvement of the DHA status during the postpartum period, as reflected by the increase of the DHA/n-6DPA ratio during this period, was higher in the non-depressed than in the depressed women (OR=0.90, p=0.04).” Similar results remained after adjusting for Study 1 or 2, parity, education level, maternal age at test moment, breastfeeding, smoking, and alcohol use (OR=0.88, p=0.03). |
N |
|
Absolute amount not specified |
“After delivery, total fatty acids in plasma phospholipids decreased significantly over time in the lactating and nonlactating women (p<0.0001).” “The amounts of ALA, DHA, and total n-3 fatty acids showed significant downward trends postpartum in both groups, whereas the amounts of EPA and DPA increased significantly after delivery.” |
N/A |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Al et al., 1995 |
Cohort |
Pregnant women (n=110) Aged 19-43 years Maastricht, Netherlands Caucasian Singleton pregnancy DBP <90 mmHg No metabolic, cardiovascular, neurological or renal disorder |
Maternal venous and umbilical vein fatty acid profiles |
10, 14, 18, 22, 26, 30, 32, 34, 36, 38, 40 weeks gestation; after delivery; 6 months after delivery |
|
Holman, 1991 |
Cohort |
Pregnant women (n=19) Aged 24-36 years Caucasian Normotensive, normal singleton pregnancies Mayo Clinic, Minnesota Controls (n=59) = staff and students from the University of Minnesota, aged 19-48 years |
Blood fatty acid composition |
36 weeks gestation, during labor, 6 weeks postpartum |
|
Amount |
Results |
Conclusion* |
|
Absolute amount not specified |
“The average total amount of fatty acid (TF) in maternal venous plasma PL increased significantly (p<0.0001) during pregnancy, but the rise in TF became less pronounced towards the end of gestation (p<0.0001).” “Total fatty acids increased from 1238.11 mg/L at week 10 to 1867.84 mg/L at week 40 of gestation, and all of the fatty acid families showed a similar course.” “The mean amount of total fatty acids in umbilical plasma phospholipids was substantially lower (p<0.0001) than all maternal values” for all fatty acid families. “In contrast to the absolute amounts of AA and DHA, the mean relative amounts of AA and DHA in umbilical plasma phospholipids were significantly (p<0.0001) higher than all maternal values.” |
N/A |
|
Normal controls of nonpregnant women of childbearing age All in mol%±SEM: 24.1±0.39 LA, 12.5±0.24 AA, 0.22±0.01 ALA, 0.53±0.03 EPA, 1.04±0.04 DPA, 3.71±0.14 DHA |
All individual PUFA were less than normal in pregnant women at 36 weeks of pregnancy than in the nonpregnant women, where EPA was 42% of normal values. “The fatty acid profile of plasma phospholipids during labor was similar to that at 36 weeks except for the subnormal LA and ALA values became significant at p<0.01 and p<0.05, respectively, and the elevated 22:5n-6 became significant at 0.001.” The fatty acid profile of plasma phospholipids for lactating women 6 weeks postpartum was similar to those during pregnancy and labor except that AA status improved, diminished ALA, and increased EPA and DPA toward normal. The fatty acid profile of plasma phospholipids for nonlactating women 6 weeks postpartum was similar to that of the lactating women, expect that abnormalities were less severe or of lower significance. |
N/A |
|
Amount |
Results |
Conclusion* |
|
Absolute amount not specified |
“Greater apparent seafood consumption predicted DHA content of mothers’ milk (p<0.006)” and “higher DHA content in mothers’ milk predicted a lower prevalence rate of postpartum depression (p<0.0001).” “Higher national seafood consumption predicted lower prevalence rates of postpartum depression (p<0.0001).” |
B |
TABLE B-1c Studies on Gestation and Birth Weight: Effects on Infants of Mothers Who Increase Seafood and/or Omega-3 Fatty Acid Intake
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
de Groot et al., 2004 |
Randomized Controlled Trial |
Pregnant women (n=79) Mean age of 29-30 years Maternal education about 4 (on an 8-point scale) Maastricht, Heerlen, Sittard, southeastern Netherlands White origin, gestational age <14 weeks, normal health, fish consumption <2 times/week No hypertensive, metabolic, cardiovascular, renal, psychiatric, or neurologic disorder |
ALA-supplemented margarine |
14 weeks gestation until delivery |
|
Smuts et al., 2003a |
Randomized Controlled Trial |
Pregnant women (n=73) Mainly African-American Aged 16-35 years Reachable by telephone Planned to deliver at the Regional Medical Center in Memphis, TN No more than four pregnancies |
DHA-enriched egg |
24-28 weeks gestation until delivery |
|
Smuts et al., 2003b |
Randomized Controlled Trial |
Pregnant women (n=291) Aged 16-36 years Mainly African-descent Plan to deliver at Truman Medical Center in Kansas City, MO Able and willing to consume eggs, access to refrigeration Singleton gestation No weight >240 pounds at baseline, cancer, lupus, hepatitis, infectious disease, diabetes, gestational diabetes, elevated blood pressure at baseline |
DHA-enriched egg |
24-28 weeks gestation until delivery |
|
Amount |
Results |
Conclusion* |
|
Experimental group (% total fatty acids): ALA-enriched high-LA margarine 25 g margarine 45.36 LA, 14.18 ALA Control group (% total fatty acids): No ALA high-LA margarine 25 g margarine/day 55.02 LA, 0.17 ALA |
Newborns in the experimental group had a significantly higher mean birth weight than those in the control group (p=0.043). No significant differences in gestational age, APGAR score, or umbilical plasma DHA concentrations in phospholipids were found between the two groups. |
B (birth weight only) |
|
High-DHA egg group: mean = 183.9±71.4 mg DHA/day ranged from 27.6 to 264.9 mg/day Ordinary egg group: mean = 35.1±13.2 mg DHA/day ranged from 0 to 36 mg/day Low egg intake group: mean = 10.8±4.0 mg DHA/day ranged from 0 to 36 mg/day |
“Mean weight, length, and head circumference of infants in the high-DHA egg group were greater than in the ordinary egg group, and gestation was 5.6 days longer.” |
B |
|
High-DHA egg group: mean = 133±15 mg DHA/egg ranged from 108 to 165 mg/ egg Ordinary egg group: mean = 33±11 mg DHA/egg ranged from 22 to 51 mg/egg |
After controlling for maternal BMI at enrollment and number of prior pregnancies, the mean difference in gestational age between the two groups was 6.0±2.3 days (p=0.009). After controlling for maternal BMI at enrollment and maternal race, the mean difference in birth weight between the two groups was not significant. |
B (gestation only) |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Haugen and Helland, 2001 |
Randomized Controlled Trial |
Pregnant women (n=37) Mean age about 27-31 years Oslo, Norway Normotensive without proteinuria, had uncomplicated term pregnancies, randomly taken from another study investigating the influence of omega-3 fatty acids on fetal, neonatal, and child development Another group had moderate preeclampsia |
Cod-liver oil supplement |
16-20 weeks gestation through pregnancy |
|
Helland et al., 2001 |
Randomized Controlled Trial |
Pregnant women (n=590) Aged 19-35 years Oslo, Norway Single pregnancies, Nulli- or primipara Intention to breastfeed No supplement of n-3 LCPUFA earlier during the pregnancy No premature births, birth asphyxia, infections, and anomalies in the infants that required special attention |
Cod-liver oil supplement |
17-19 weeks gestation until 3 months after delivery |
|
Amount |
Results |
Conclusion* |
|
Cod-liver oil group: 10 mL/day Corn-oil group: 10 mL/day |
There were no significant differences in gestational age between the four groups (cod-liver oil group, corn oil group, preeclamptic group, and the normotensive group). Birth weight was significantly higher in the corn oil group compared to the cod-liver oil group (p<0.05) and significantly higher in the normotensive group compared to the preeclamptic group (p<0.0001). |
A (birth weight only) |
|
10 mL/day cod-liver oil vs. corn oil Cod-liver oil group: 803 mg of EPA/10 mL; 1183 mg DHA/10 mL Corn-oil group: 0 mg of EPA/10 mL; 8.3 mg DHA/10 mL |
“There were no significant differences in gestational length or birth weight between the two supplement groups. Birth length, head circumference, and placental weight were also similar in the 2 supplement groups.” |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Olsen et al., 2000 |
Randomized Controlled Trial |
Pregnant women (n=1619) 19 hospitals in Denmark, Scotland, Sweden, England, Italy, Netherlands, Norway, Belgium, and Russia Participated in one of six previous trials (four prophylactic trials and two therapeutic trials) |
Fish-oil supplement |
20 weeks (prophylactic) or 33 weeks (therapeutic) gestation, delivery |
|
Olsen et al., 1992 |
Randomized Controlled Trial |
Pregnant women (n=533) Mean age 29 years Aarhus, Denmark Main midwife clinic, covers a well-defined geographic area No placental abruption in previous pregnancy or serious bleeding in current pregnancy; no prostaglandin inhibitors regularly No multiple pregnancy, allergy to fish, and regular intake of fish oil |
Fish-oil supplement |
Enrolled at 30 weeks gestation; end time not specified |
|
Amount |
Results |
Conclusion* |
|
2.7 g/day fish oil vs. olive oil in the prophylactic trials 6.1 g/day fish oil vs. olive oil in the therapeutic trials |
In the trial of women who experienced preterm delivery in an earlier pregnancy, those randomized to fish oil had statistically significant longer gestation duration (difference = 8.5 days) compared to those randomized to olive oil (p=0.01). In the trial of women who experienced preterm delivery in an earlier pregnancy, those randomized to fish oil had children with a significantly higher mean birth weight (difference = 208.7 g) compared to those randomized to olive oil (p=0.02). In the trial of women with threatening preeclampsia in the current pregnancy, the mean difference of duration until delivery was 8.8 days less for those randomized to fish oil compared to those randomized to olive oil (p=0.19). In the trial of women with suspected intrauterine growth retardation in the current pregnancy, the mean difference of weight for gestational age was 29 g higher in those randomized to fish oil compared to those randomized to olive oil (p=0.75). |
B |
|
2.7 g/day fish oil vs. olive oil |
The average gestational length for those in the fish-oil group was 4 days longer (95% CI 1.5-6.4, p<0.005) than those in the olive oil group. The average gestational length for those in the fish-oil group was 2.8 days longer (95% CI 0.8-4.8, p<0.01)) than those in the olive-oil and control groups. Birth weight (p=0.07) and length (p=0.1) trended higher in the fish-oil group than in the olive-oil group (3 way ANOVA between fish oil, olive oil, no oil). |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Olsen and Secher, 1990 |
Randomized Controlled Trial |
Pregnant women (n=5022) Aged 15-44 years London People’s League of Health, 1946 Attending antenatal clinics of 10 hospitals No disease or physical abnormality |
EPA/DHA supplement from halibut oil |
Enrolled at <24 weeks gestation; treatment lasts for <15 weeks (n=288), 16-19 weeks (n=411), 20-23 weeks (n=414), or 24+ weeks (n=417) |
|
People’s League of Health, 1946 |
Randomized Controlled Trial |
Pregnant women (n=5022) London Not beyond the 24th week of pregnancy No physical disease or abnormality |
n-3 supplement |
|
|
People’s League of Health, 1942 |
Randomized Controlled Trial |
Pregnant women (n=5022) London |
Additional diet, which includes hali-but liver oil |
Enrolled if due date more than 16 weeks away; until delivery |
|
Amount |
Results |
Conclusion* |
|
0.1 g/day of EPA+DHA from halibut oil in supplement vs. no supplement Supplement includes 0.26 g ferrous iron; 0.26 g calcium; minute quantities of iodine, manganese, and copper; 0.6 g thiamin/g; 0.1 g vitamin C; 0.36 g halibut liver oil |
“In primiparae, a 19.9% (p=0.012) reduction in the odds of delivering earlier than 40 weeks was seen in the treatment group, whereas in multiparae a reduction of 21.2% (p=0.028) was seen,” compared to the control group. “No significant effects were seen on the odds of delivering after 40 weeks of gestation.” “No significant effects were seen on average birth weight.” |
B (gestation only) |
|
|
“A smaller incidence of prematurely was revealed among the treated women, and this is particularly significant since about 50% of infant deaths under 1 month are due to prematurely.” |
B |
|
Weekly intake score for consumption of “the more important foodstuffs” such as milk, butter, wholemeal bread, fresh vegetables, fatty fish, fruit, eggs, etc. Additional diet: 0.26 g ferrous iron; 0.26 g calcium; minute quantities of iodine, manganese, and copper; 1 g adsorbate of vitamin B1; 100 mg vitamin C; 0.36 g halibut liver oil (vitamins A and D) |
Among primigravida women, 20.1±1.10% of those who received additional diet experienced a preterm delivery compared to 23.9±1.10% of those who did not receive additional diet. This difference was statistically significant. Among multiparae women, 20.1±1.33% of those who received additional diet experienced a preterm delivery compared to 24.2±1.33% of those who did not receive additional diet. This difference was statistically significant. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Lucas et al., 2004 |
Cohort |
Postpartum women (n=491) and their infants Mean age of 23.7 years Inuit 14 coastal villages of Nunavik and southern Quebec Delivered at Tulattavik Health Center (Ungava Bay) or Inuulitsivik Health Center (Hudson Bay) |
Cord venous sample |
At delivery |
|
Amount |
Results |
Conclusion* |
|
Tertiles of EPA (% of total fatty acids): Tertile 1 = <0.21 Tertile 2 = 0.21-0.39 Tertile 3 = >0.39 Tertiles of DHA (% of total fatty acids): Tertile 1 = <2.99 Tertile 2 = 2.99-4.03 Tertile 3 = >4.03 Tertiles of %n-3 HUFA (% of total HUFA): Tertile 1 = <18.60 Tertile 2 = 18.60-22.96 Tertile 3 = >22.96 |
After adjusting for weight gain during pregnancy, gestational diabetes, cord blood mercury, lead, and PCB congener 153, those in the third tertile of n-3 HUFA (% of total HUFA) had significantly longer gestation (278.4 days) compared to those in the first tertile (273.0 days) (p<0.05). After adjusting for pre-pregnancy weight, weight gain during pregnancy, parity, smoking status during pregnancy, gestational diabetes, age, cord blood mercury, and PCB congener 153, those in the third tertile of n-3 HUFA (% of total HUFA) had babies with a higher birth weight (3551 g) compared to those in the first tertile (3475 g), but this difference was not significant. There were no significant differences in birth weight or gestation based on the tertiles of EPA and DHA in the cord blood. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Oken et al., 2004 |
Cohort |
Pregnant women (n=2109) Aged 14-44 years 16% Black, 7% Hispanic-American, 6% Asian-American Massachusetts Project Viva |
Seafood |
Last menstrual period until enrollment, 3 months prior to 26-28 weeks of gestation, the month prior to delivery |
|
Olsen and Secher, 2002 |
Cohort |
Pregnant women (n=8729) Aarhus, Denmark Gave birth to singleton, liveborn babies without detected malformations Had not consumed fish-oil supplements |
Seafood |
From when first knew of pregnancy until completion of questionnaires at 16 and 30 weeks gestation |
|
Amount |
Results |
Conclusion* |
|
Seafood tertiles: None or <1 serving/month, the remaining subjects were divided into tertiles with the highest intake group used as the referent First trimester quartiles of EPA+DHA: Quartile 1 = 0.00-0.05 Quartile 2 = 0.06-0.12 Quartile 3 = 0.12-0.24 Quartile 4 = 0.24-2.53 Second trimester quartiles of EPA+DHA: Quartile 1 = 0.00-0.05 Quartile 2 = 0.06-0.12 Quartile 3 = 0.12-0.23 Quartile 4 = 0.24-2.71 Third trimester quartiles of EPA+DHA: Quartile 1 and 2 = 0.00-0.06 Quartile 3 = 0.60-0.11 Quartile 4 = 0.11-1.72 |
After adjusting for enrollment site, infant sex, and maternal age, height, intrapartum weight gain, pre-pregnancy BMI, race/ethnicity, smoking during pregnancy, education, and gravidity: Significant negative trends based on EPA+DHA intake were found for the first trimester [birth weight (p=0.01) and fetal growth (p=0.001)], the second trimester [fetal growth (p=0.03)], and the third trimester [birth weight (p=0.001) and fetal growth (p=0.003)]; No other significant trends were observed for change in birth weight, fetal growth or length of gestation with EPA+DHA intake during the three trimesters; Significant negative trends were observed for change in birth weight and fetal growth with seafood consumption, but only during the first trimester (p=0.05 and p=0.08, respectively); and No other significant trends were observed for change in birth weight, fetal growth, or length of gestation with seafood intake during the first two trimesters. |
B |
|
0.0, 0.5, 2.0, 4.0, 20.0, 28.0 serving/28 days Hot fish meal: 144 g fish/serving 1627 µg n-3 fatty acids/serving Fish sandwich: 29 g fish/serving 431 µg n-3 fatty acids/serving Fish salad: 50 g fish/serving 149 µg n-3 fatty acids/serving |
“Low birth weight, preterm birth, and intrauterine growth retardation all tended to decrease with increasing fish consumption, and mean birth weight, duration of gestation, and birth weight adjusted for gestational age tended to increase with increasing fish consumption.” Low consumption of seafood was a strong risk factor for preterm delivery and low birth weight. The associations were strongest below a daily intake of 0.15 g long change n-3 fatty acids or 15 g fish. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Grandjean et al., 2001 |
Cohort |
Singleton term births (n=182) Faroe Islands Delivered at the National Hospital in Torshavn Birth at >36 weeks of gestation; no congenital neurological disease |
Maternal and cord serum and seafood intake |
Maternal blood taken at week 34, cord blood taken at delivery, questionnaire administered 2 weeks after parturition |
|
Olsen et al., 1991 |
Cohort |
Mothers of live-born singleton infants (n=99) Mean age about 27 years Faroese (n=62) and Danish women (n=37) Delivered at the Landssjukrahusid and Aarhus Kommenehospital No preeclampsia, rhesus immunization, insulin-dependent diabetes mellitus, or twin pregnancies |
Peripheral venous blood sample |
5-48 hours after delivery |
|
Amount |
Results |
Conclusion* |
|
Information on fish species or portion sizes was not collected Fish dinners/week: 0, 1, 2, ≥3 Whale meat dinners/month: 0, 1, ≥2 Whale blubber dinners/month: 0, 1-2, >2 |
Gestational length showed a significant positive association with cord serum DHA concentration (p<0.001) and DTA (p=0.004). After adjusting for nonsmoking, average-height and nulliparous mother with term birth of male baby, birth weight showed a significant positive association with cord serum ETA (p=0.001), EPA (p=0.015), and DPA (p=0.002). After adjusting for gender, parity, gestational length, smoking, and maternal height, birth weight decreases by 246 g for every one unit increase in cord serum EPA concentration (%) (p=0.037). |
B |
|
Faroese women: Mean of 0.83±0.039% EPA Mean of 2.08±0.059% DPA Mean of 5.87±0.12% DHA Mean of 12.07±0.15% AA Danish women: Mean of 0.61±0.051% EPA Mean of 2.08±0.076% DPA Mean of 4.65±0.159% DHA Mean of 12.07±0.19% AA |
There were no significant differences in gestational age (p=0.3) and birth weight (p=0.1) between the two groups. After controlling for maternal pre-pregnant weight, height, age, parity, marital status, smoking, and employment during pregnancy a significant association was found between the (3/6) ratio from blood and gestational age in the Danish women (p=0.02) but not in the Faroese women (p=0.6). |
N |
|
Amount |
Results |
Conclusion* |
|
The Orcandians eat 30% more fish than the Aberdonians, but absolute amount undetermined |
Mean birth weight of the infants born to residents of Orkney Islands was 3521 g and for residents of Aberdeen was 3287 g (p=0.01). Gestational age was 0.36 weeks longer in the Orkney women than in the Aberdeen women (p=0.01). 18.3% of infants born to Orkney women and 10.0% of infants born to Aberdeen women were over the 90th percentile for birth weight (corrected for gestational age and parity) (p=0.01). 4.8% of infants born to Orkney women and 12.2% of infants born to Aberdeen women were below the 10th percentile for birth weight (corrected for gestational age and parity) (p=0.01). Being a resident of Orkney explains a significant proportion of the difference in birth weights between Orkney and Aberdeen women (R2 = 0.489). |
B |
TABLE B-1d Studies on Development (Anthropometry, Visual Acuity, and Cognition): Effects on Infants of Mothers Who Increase Seafood and/or Omega-3 Fatty Acid Intake
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Cohen et al., 2005 |
Review |
Aggregated 8 randomized controlled trials (one study of maternal dietary supplementation and seven studies of formula supplementation) |
DHA supplement |
|
|
Jensen et al., 2005 |
Randomized Controlled Trial |
Pregnant women (n=114 in DHA group; n=113 in control group) Aged 18-40 years Houston, TX White (75% DHA group; 79% control group) African American (19% DHA group; 13% control group) Gestational age >37 weeks Infant birth weight 2500-4200 g No chronic maternal disorders as well as major congenital anomalies and obvious gastrointestinal or metabolic disorders of the infant |
DHA supplement |
Day 5 after delivery until 4 months postpartum |
|
Amount |
Results |
Conclusion* |
|
|
An increase in maternal intake of DHA during pregnancy of 1 g/day will increase child IQ by 0.8-1.8 points. “Prenatal maternal DHA intake increasing the child plasma (RBC) DHA phospholipid fraction by 1% has the same impact on cognitive development as formula DHA supplementation that increases the child’s plasma (RBC) DHA phospholipid fraction by 1%.” “Because typical DHA intake associated with fish consumption is well under 1 g/day, changes in fish consumption will result in IQ effects amounting to a fraction of a point,” but they are not clinically detectable. |
B |
|
DHA capsule: Algal triacylglycerol 200 mg DHA/day Control capsule: Soy and corn oil |
There were no significant differences in visual acuity (from either the Teller Acuity Card or Sweep VEP) at 4 or 8 months of age between the two groups. There were no significant differences in mean transient VEP latency at 4 and 8 months of age between the two groups; but the transient VEP amplitude was significantly lower in the infants of the DHA group compared to the infants of the control group. There were no significant differences in Gesell Gross Motor Inventory, CAT, CLAMS DQ, or Bayley MDI between the two groups at 12 or 30 months of age; but Bayley PDI at 30 months of age was 8.4 points higher (p=0.005) in infants of the DHA group compared to infants of the control group. |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Dunstan et al., 2004 |
Randomized Controlled Trial |
Pregnant women (n=83) Atopic pregnancies Western Australia History of doctor diagnosed allergic rhinitis and/or asthma One or more positive skin prick test to house mites; grass pollens; molds; cat, dog, or cockroach extracts Nonsmokers No other medical problems, complicated pregnancies, seafood allergy, or >2 fish meals/week Term, healthy infants considered at high risk of allergic disease |
Fish-oil supplement |
20 weeks gestation until delivery |
|
Jensen et al., 2004 |
Randomized Controlled Trial |
Breast-feeding mothers (n=89 in treatment group; n=85 in placebo group) |
DHA supplement |
Delivery until 4 months postpartum |
|
Amount |
Results |
Conclusion* |
|
Fish-oil group: 3.7 g/day fish oil 56% DHA and 27.7% EPA 4 capsules/day Olive-oil group: 66.6% n-9 oleic acid and <1% n-3 PUFA 4 capsules/day |
Breast milk concentrations of DHA, DPA, and EPA were significantly higher (p<0.001) and AA was significantly lower (p=0.045) in fish-oil supplemented mothers compared with controls. “There were no significant differences in the detection or level of free cytokines or IgA between the 2 groups.” |
N/A |
|
200 mg/day of DHA vs. placebo |
There were no significant differences between the two groups in visual function or neurodevelopment until 30 months of age. At age 30 months, the Bayley PDI of infants whose mothers were randomized to DHA was 0.55 standard deviations higher (p<0.01) than that of infants whose mothers were randomized to the placebo. There were no significant differences between the two groups in visual function; transient VEP; sweep VEP; stereoacuity; and gross and fine motor, executive, perceptual/visual or verbal domains at age 5. At age 5, infants whose mothers were randomized to DHA had significantly higher Sustained Attention Subtest of the Leiter International Performance Scale than those whose mothers were randomized to the placebo (p<0.008). |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Helland et al., 2003 |
Randomized Controlled Trial |
Pregnant women (n=48 in cod-liver oil group; n=36 in corn oil group) Aged 19-35 years Oslo, Norway Healthy women with, singleton pregnancy, nulli- or primiparous, intention to breastfeed No supplement of n-3 LCPUFA earlier during pregnancy, premature births, birth asphyxia, general infections, or anomalies in the infants that required special attention |
Cod-liver oil supplement |
From 18 weeks of pregnancy until 3 months after delivery |
|
Amount |
Results |
Conclusion* |
|
Cod-liver oil: 10 mL/day 1183 mg DHA, 803 mg EPA Corn oil: 10 mL/day 4747 mg LA, 92 mg ALA |
K-ABC scores were significantly higher for the subset MPCOMP among children from the cod-liver oil group compared to the corn oil group (p=0.049). The scores for the other subtests (SEQPROC, SIMPROC, NONVERB) were also higher in the cod-liver oil group compared to the corn oil group, but they were not significant. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Auestad et al., 2001 |
Randomized Controlled Trial |
Infants (n=294 formula fed; n=165 breastfed) Kansas City, MO; Little Rock, AR; Pittsburgh, PA; Tucson, AZ Good health, term status, either ≤9 days of age (formula group) or ≤11 days of age and currently breastfeeding (breastfeeding group), birth weight ≥2500 g, 5-minute APGAR score ≥7, ability to tolerate milk-based formula or breast milk, guardian or parent agreement to feed the assigned study formula ad libitum according to the study design No evidence of significant cardiac, respiratory, ophthalmologic, gastrointestinal, hematologic, or metabolic disease; milk-protein allergy; or a maternal medical history known to have proven adverse effects on the fetus, tuberculosis, HIV, perinatal infections, or substance abuse 61-74% European American 60-80% mothers married Mean mother’s age about 29 years Mean mother’s education about 14 years |
Fish oil/fungal oil and egg-derived triglyceride supplemented formulas |
9-11 days after birth until 12 months of age |
|
Amount |
Results |
Conclusion* |
|
Fish oil and fungal oil supplemented preterm formula: 0.46 g AA/100 g total fatty acids ≤0.04 g EPA/100 g total fatty acids 0.13 g DHA/100 g total fatty acids Egg-derived triglyceride supplemented preterm formula: 0.45 g AA/100 g total fatty acids No detected EPA 0.14 g DHA/100 g total fatty acids Control formula: No detected AA, EPA, DHA |
The vocabulary expression score at 14 months was significantly higher in the fish/fungal group than in the egg-TG group (p<0.05). Smiling and laughter was significantly higher in the control group than in the egg-TG group (p=0.05). No other development, cognition, vocabulary, or temperament outcomes presented were significantly difference between the formula groups. No significant differences were found between groups for weight, length, and head circumference or visual acuity. |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Helland et al., 2001 |
Randomized Controlled Trial |
Pregnant women (n=590) Aged 19-35 years Oslo, Norway Single pregnancies, nulli-or primipara Intention to breastfeed No supplement of n-3 LCPUFA earlier during the pregnancy No premature births, birth asphyxia, infections, and anomalies in the infants that required special attention |
Cod-liver oil supplement |
17-19 weeks gestation until 3 months after delivery |
|
McCann and Ames, 2005 |
Review |
Summary of observational, RCTs, other experimental and animal studies |
LCPUFA supplement |
|
|
Amount |
Results |
Conclusion* |
|
10 mL/day cod-liver oil vs. corn oil Cod-liver oil: 803 mg of EPA/10 mL; 1183 mg DHA/10 mL Corn oil: 0 mg of EPA/10 mL; 8.3 mg DHA/10 mL |
“There were no significant differences in gestational length or birth weight between the 2 supplement groups. Birth length, head circumference, and placental weight were also similar in the 2 supplement groups.” |
N |
|
|
“Evidence from chronic dietary restriction rodent studies … shows that the addition of DHA to diets of animals whose brain concentration of DHA have been severely reduced restored control performance levels.” “Formula comparison and maternal supplementation studies in humans and ALA dietary restriction studies in nonhuman primates both link the availability of n-3 LCPUFAs to the development of visual attention” and higher DHA status to enhanced neuromotor development. RCTs in humans have often shown no effect of “LCPUFA supplementation on cognitive or behavioral performance and some reviewers have considered that, overall, the evidence was insufficient to conclude that LCPUFA supplementation benefited development.” |
B |
|
Amount |
Results |
Conclusion* |
|
|
“Breastfeeding, which supplies preformed LCPUFA, is the preferred method of feeding for healthy infants and is strongly supported.” “Infant formulas should contain at least 0.2% of total fatty acids as DHA and 0.35% as AA; formulas for preterm infants should include at least 0.35% DHA and 0.4% AA.” There is an absence of published studies showing direct functional benefits of supplementation of LCPUFA and studies to determine if the variability in LCPUFA status among pregnant women is related to functions in either the mother or infant. “It seems prudent for pregnant and lactating women to include some food sources of DHA in their diet.” |
B |
|
|
“There appears to be no detectable reduction in plasma n-3 LCPUFA concentrations during pregnancy, whereas there is a clear decline during the early postpartum period.” “Results of randomized clinical studies suggest that n-3 LCPUFA supplementation during pregnancy does not affect the incidences of pregnancy-induced hypertension and preeclampsia without edema.” “n-3 LCPUFA supplementation may cause modest increases in the duration of gestation, birth weight, or both.” “To date there is little evidence of harm as a result of n-3 LCPUFA supplementation during either pregnancy or lactation.” |
B |
|
Amount |
Results |
Conclusion* |
|
Carbohydrate (g) 182-218, 218-258, >258 Protein (g) 55-66, 66-79, >79 Total fat (g) 55-68, 68-84, >84 Saturated fat (g) 21-27, 27-35, >35 Polyunsaturated fat (g) 9-12, 12-16, >16 Monounsaturated fat (g) 19-24, 24-30, >30 Calcium (mg) 759-938, 939-1127, >1127 Potassium (mg) 2177-2582, 2583-3021, >3021 Magnesium (mg) 207-254, 255-308, >308 Protein/carbohydrate 0.26-0.30, 0.31-0.35, >0.35 Animal protein (g) 35-44, 44-53, >53 Omega-3 fatty acids (g) 0.03-0.09, 0.10-0.27, >0.27 |
After adjusting for sex, child’s age for blood pressure, and maternal pregnancy energy intake, a significant inverse association was found between omega-3 fatty acids and offspring blood pressure at age 7.5 years (p=0.04). After adjusting for sex, child’s age for blood pressure, and maternal pregnancy energy intake, there were no significant differences in offspring blood pressure at age 7.5 years based on maternal intake of carbohydrate, protein, total fat, saturated fat, polyunsaturated fat, monounsaturated fat, calcium, potassium, magnesium, protein/carbohydrate or animal protein. After adjusting for measurement factors, current anthropometry, maternal and social factors, birth weight, and gestation, there was a significant positive association found between maternal intake of carbohydrates and offspring blood pressure at 7.5 years (p=0.04). After adjusting for measurement factors, current anthropometry, maternal and social factors, birth weight, and gestation, there were no significant differences between the tertiles of maternal intake of protein, total fat, saturated fat, polyunsaturated fat, monounsaturated fat, calcium, potassium, magnesium, protein/carbohydrate, animal protein, or omega-3 fatty acid and offsprings’ systolic blood pressure at age 7.5 years. |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Oken et al., 2005 |
Cohort |
Mother-infant pairs (n=135) Aged <30 years (n=16) Aged 30-34 years (n=53) Aged ≥35 years (n=31) 82% White; 18% non-White 80% college or graduate degree Massachusetts Singleton pregnancy, were able to complete forms in English, did not plan to move out of the study area before delivery Project Viva |
Seafood |
Second trimester of pregnancy |
|
Colombo et al., 2004 |
Cohort |
Infants (n=70) Mean gestation 39.29 weeks Mean birth weight 3248.57 g Mean APGAR score (1 min) 7.94 Mean APGAR score (5 min) 8.80 Mean education (11.77 years for mother and 11.88 for father) 77% African American 21% Caucasian 1% Hispanic Kansas |
DHA-enriched egg |
24-28 weeks gestation until delivery |
|
Amount |
Results |
Conclusion* |
|
Number of servings/week: Canned tuna fish (3-4 oz/serving) Shrimp/lobster/scallop/clam (1 serving) Dark meat fish (3-5 oz/serving) Other fish (3-5 oz/serving) 6 responses from never or less than 1/month to 1 or more servings/day |
After controlling for maternal hair mercury level, age, race/ethnicity, education, marital status, infant sex, gestational age at birth, birth weight for gestational age, breast-feeding duration and age at cognitive testing: Each 1 serving/week increase of fish intake increases the VRM score by 4 points (%novelty preference; 95% CI 1.3-6.7). After controlling for maternal seafood intake, age, race/ethnicity, education, marital status, infant sex, gestational age at birth, birth weight for gestational age, breast-feeding duration, and age at cognitive testing: Each 1 ppm increase in maternal hair mercury levels decreases the VRM score by 7.5 points (%novelty preference; 95% CI −13.7 to −1.2). |
B |
|
This study is a follow-up to an RCT High-DHA eggs: 135 mg DHA/egg Ordinary eggs: 35 mg DHA/egg |
“Infant red blood cell DHA level was unrelated to subsequent attentional measures, but maternal red blood cell DHA was consistently predictive of later attentional outcomes.” “Infants whose mothers had higher levels of DHA at birth showed accelerated developmental courses in attention across the 1st year.” Percent of time spent looking in orienting increased over time in both the high- and low-DHA groups, but it was larger in the high-DHA group compared to the low-DHA group at 4, 6, and 8 months. Percent of time spent looking in sustained attention declined over time in both groups, but it was smaller in the high-DHA group compared to the low-DHA group at 4, 6, and 8 months. Percent of time spent looking in attention termination was larger at 4 months in the low-DHA group compared to the high-DHA group, and then declined and leveled off at 6 months in both groups. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Daniels et al., 2004 |
Cohort |
Infants (n=1054) Mothers’ mean age = 29 years Majority of mothers with at least an O (moderate) level education Bristol, UK Singleton, term births Avon Longitudinal Study of Parents and Children (ALSPAC) |
Seafood |
Maternal fish intake: 32 weeks of gestation Breastfeeding practices: 15 months after birth Infant fish intake: 6 and 12 months after birth Total mercury concentration: Cord blood at birth |
|
Sakamoto et al., 2004 |
Cohort |
Pregnant women (n=63) Aged 21-41 years Japan Planning to deliver at Munakata Suikokai General Hospital, Fukuoka Healthy |
Maternal blood and umbilical cord blood lipids |
Umbilical cord blood at birth and maternal blood 1 day after parturition before breakfast |
|
Amount |
Results |
Conclusion* |
|
Maternal fish intake categories (during pregnancy): 1 = Rarely/never 2 = 1 meal/2 weeks 3 = 1-3 meals/week 4 = 4+ meals/week Child fish intake categories (6 months of age): 1 = Rarely/never 2 = 1+ meal/week Child fish intake categories (12 months of age): 1 = Rarely/never 2 = 1+ meal/week |
Children whose mothers ate 1-3 fish meals/week and 4+ fish meals/week had significantly lower odds of low MCDI scores for social activity (OR=0.6, 95% CI 0.5-0.8 and OR=0.7, 95% CI 0.5-0.9, respectively) than the children whose mothers rarely or never ate fish during pregnancy. Children whose mothers ate 1-3 fish meals/week and 4+ fish meals/week had significantly lower odds of low DDST scores for language (OR=0.7, 95% CI 0.5-0.9 and OR=0.7, 95% CI 0.5-0.9, respectively) than the children whose mothers rarely or never ate fish during pregnancy. Children who ate 1+ fish meals/week had significantly lower odds of low MCDI scores for vocabulary comprehension (OR=0.7, 95% CI 0.5-0.8) and social activity (OR=0.7, 95% CI 0.6-0.9) and total DDST scores (OR=0.8, 95% CI 0.6-0.9). All other odds ratios presented were nonsignificant. |
B |
|
Unspecified |
In all cases, fetal RBC-Hg levels (13.4 ng/g) were statistically higher than maternal RBC-Hg levels (8.41 ng/g) (p<0.01). “A strong correlation was observed in RBC-Hg between mothers and fetuses (r=0.92, p<0.001).” “Maternal RBC-Hg concentrations showed significant correlation coefficients with maternal plasma EPA (r=0.36, p<0.001) and DHA (r=0.33, p<0.005) concentrations.” “Fetal RBC-Hg concentrations showed a significant positive correlation with fetal plasma EPA (r=0.32, p<0.05) and DHA (r=0.35, p<0.01).” |
N/A |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Willatts et al., 2003 |
Cohort |
Mother and infant pairs (n=96) Term pregnancy and infant birth weight >2499 g Dundee |
DHA and AA content in maternal red blood cells |
34-36 weeks gestation |
|
Cheruku et al., 2002 |
Cohort |
Pregnant women (n=17) Men aged 29 years in the high-DHA group Men aged 24 years in the low-DHA group White (n=14) Hispanic (n=3) Windham, CT ≥4 hours of crib time in the first and second days postpartum No history of chronic hypertension, hyperlipidemia, renal or liver disease, heart disease, thyroid disorders, multiple gestations, or pregnancy-induced complications No drugs that affect the respiration of newborns, such as magnesium sulfate and butorphanol |
Maternal plasma DHA |
Day 1 and day 2 postpartum |
|
Amount |
Results |
Conclusion* |
|
Absolute DHA and AA levels in blood unspecified |
After adjusting for maternal education, social class, birth weight, gestation, type of feeding at birth, and infant age at time of assessment: “There was a significant negative relation between maternal DHA and peak look duration (p<0.05), and a significant positive relation between maternal DHA and visual acuity (p<0.01)” at 4 months of age. The relation between AA and peak look duration and visual acuity at 4 months of age were not significant. “These results suggest that higher maternal DHA status is related to more efficient information processing and improved visual acuity development in 4-month-old infants.” |
B |
|
High-DHA group (maternal plasma): >3.0% by weight of total fatty acids Low-DHA group (maternal plasma): ≤3.0% by weight of total fatty acids |
On day 2 postpartum, the low-DHA group had significantly higher sleep-wake transition (% of time in crib) and less wakefulness (% time in crib) than the high-DHA group (p<0.05). There was a significant group effect for active sleep time (p=0.004) and active:quick sleep time (p=0.001), these times being shorter in the high-DHA group than in the low-DHA group. “Differences in the prenatal supply of LCPUFAs, especially DHA, may modify brain phospholipids and affect neural function.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Haggerty et al., 2002 |
Cohort |
Mothers, smokers (n=11) Mothers, nonsmokers (n=13) Aberdeen, Scotland Uncomplicated, full-term pregnancies Perfusion on term placentas delivered vaginally or by elective Caesarean section from otherwise uncomplicated pregnancies |
Placental tissue lipids |
Within 20 minutes of delivery |
|
Innis et al., 2001 |
Cohort |
Infants (n=83) Term Birth weight 2500-4500 g Mean mother’s age of 32 years British Colombia Intend to breast-feed for 3 months, no solid foods for at least the first 4 months after birth No mothers with substance abuse, communicable diseases, metabolic or physiologic problems, infections likely to influence fetal growth, or multiple births No infants with evidence of metabolic or physical abnormalities |
Fatty acids in blood from infants and milk from mothers |
2 months of age |
|
Amount |
Results |
Conclusion* |
|
Unspecified |
The rates of transfer of LA and AA per perfused area were not different between the groups; “neither was the rate of placental transfer of ALA and DHA affected by smoking during pregnancy.” “In the non-smoking control group the placenta selectively transferred polyunsaturated fatty acids to the fetus in the order DHA > AA > ALA > LA. The order of selectivity was unaltered in placentas from smokers, but the addition of ethanol to the perfusion medium altered the order of selectivity to AA > ALA > LA > DHA.” “The presence of ethanol in the perfusate at a concentration of 2 mg/ml significantly reduced (p<0.01) the absolute rate of transfer of ALA and DHA.” |
N/A |
|
Infant DHA: (g/100 g fatty acids) Plasma phospholipids = 2.2-8.0 RBC PE = 6.3-13.0 PC = 1.4-4.6 Infant AA: (g/100 g fatty acids) Plasma phospholipids = 8.1-15.8 RBC PE = 20.2-27.8 PC = 5.6-9.7 Mother’s milk: (g/100 g milk fatty acids) DHA = 0.10-2.50 AA = 0.20-0.81 LA = 6.30-21.50 LNA = 0.50-4.10 |
“The ability to correctly discriminate a retroflex compared with dental phonetic contrast at 9 months of age was positively correlated with the plasma phospholipid DHA (p<0.02) and the RBC PE at 2 months of age (p=0.02).” “There were no significant correlations between the infants’ AA status and the ability to discriminate the native or nonnative language contrasts.” “There were no significant correlations between the infant DHA or AA status at 2 months of age and test scores for novelty preference, or the job search task, with adjustments for covariates included in the model.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Otto et al., 2001 |
Cohort |
Pregnant women (n=57) Mean age around 30 years Southern Limburg, Netherlands No metabolic, cardiovascular, neurologic, or renal disorders No medications, except multivitamins and iron supplements Singleton pregnancy Term delivery No blood transfusions in the perinatal period |
Plasma phospholipids |
36-37 weeks gestation; 2-5 days after delivery; 1, 2, 4, 8, 16, 32, 64 weeks postpartum |
|
Williams et al., 2001 |
Cohort |
Boys and girls (n=435) Mean age of 3.5 years Born in last 6 months of the Avon Longitudinal Study of Parents and Children (ALSPAC) enrollment period Healthy term infants |
Seafood |
During pregnancy for the mothers and at 4 weeks, 4 months, and 6 months for the infants |
|
Amount |
Results |
Conclusion* |
|
Absolute amount not specified |
“After delivery, total fatty acids in plasma phospholipids decreased significantly over time in the lactating and nonlactating women (p<0.0001).” “The amounts of ALA, DHA, and total n-3 fatty acids showed significant downward trends postpartum in both groups, whereas the amounts of EPA and DPA increased significantly after delivery.” |
N/A |
|
Oily fish consumption categories: 1 = Never or rarely 2 = Once every 2 weeks 3 = More than once every 2 weeks White fish = cod, haddock, plaice, and fish fingers Oily fish = pilchards, sardines, mackerel, tuna, herring, kippers, trout, and salmon |
After adjusting for breastfeeding, sex, maternal education, maternal age, housing tenure, financial difficulties, maternal smoking, number of older siblings in household, child care, maternal job status, mother is a vegetarian, mother’s fish eating habits: “Mothers who ate oily fish at least once every 2 weeks during pregnancy were more likely to have children who achieved foveal steroacuity than were the mothers who never ate oily fish (OR=1.57, 95% CI 1.00-2.45),” but this was not significant. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Haggerty et al., 1999 |
Cohort |
Pregnant women (n=10) Mean age of 31.3 years In last trimester of pregnancy 31-38 weeks gestational age Aberdeen, Scotland Healthy |
Fatty acid composition of maternal perfusate |
31-38 weeks gestation |
|
Haggerty et al., 1997 |
Cohort |
Term placentae (n=9) Mean weight of 566 g Delivered vaginally or by elective caesarean section Uncomplicated pregnancies Nonsmokers |
Placental tissue lipids |
Within 20 minutes of delivery |
|
Al et al., 1995 |
Cohort |
Pregnant women (n=110) Aged 19-43 years Maastricht, Netherlands Caucasian Singleton pregnancy DBP <90 mmHg No metabolic, cardiovascular, neurological or renal disorder |
Maternal venous and umbilical vein fatty acid profiles |
10, 14, 18, 22, 26, 30, 32, 34, 36, 38, 40 weeks gestation; after delivery; 6 months after delivery |
|
Amount |
Results |
Conclusion* |
|
Unspecified |
“When perfused with fatty acids in the ratios found in maternal circulating triglyceride, the human placenta selectively transfers PUFA to the fetus in the order: DHA > ALA > LA > AA.” “The ultimate source of fatty acids for the placenta is important for estimates of the likely supply of individual PUFA/LCPUFA to the fetus in utero.” “The biggest determinant of transfer of individual fatty acids from the mother to fetus is the supply of fatty acids available in the maternal circulation.” |
N/A |
|
Unspecified |
“The order of selectivity for placental transfer to the fetal circulation was DHA > ALA > LA > oleic acid, whilst the proportion of AA transferred was actually lower than that for oleic acid.” “There was no evidence of chain elongation of LA or ALA to any LCPUFA of the n-6 or n-3 series in the perfused placenta.” |
N/A |
|
Absolute amount not specified |
“The average amount of total fatty acid in maternal venous plasma phospholipids increased significantly (p<0.0001) during pregnancy, but the rise in total fatty acids became less pronounced towards the end of gestation (p<0.0001).” Total fatty acids increased from 1238.11 mg/L at week 10 to 1867.84 mg/L at week 40 of gestation, and all of the fatty acid families showed a similar course. “The mean amount of total fatty acids in umbilical plasma phospholipids was substantially lower (p<0.0001) than all maternal values” for all fatty acid families. “In contrast to the absolute amounts of AA and DHA, the mean relative amounts of AA and DHA in umbilical plasma phospholipids were significantly (p<0.0001) higher than all maternal values.” |
N/A |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Clandinin et al., 1980b |
Cohort |
Male infants (n=14) Female infants (n=7) Died within 3 days of birth Toronto, Canada Infants died from intrapartum asphyxia, congenital heart disease, sudden infant death syndrome, diaphragmatic hernia, and accidental causes Infants were of normal body weight and weight for length, with the exception of two infant males; infants had normal head circumference, with the exception of one infant male No infections or gastrointestinal disorders, apparently normally nourished, and growing reasonably well until the time of death |
Tissue fatty acid content from frontal and occipital brain lobes and cerebellum |
16 hours postmortem |
|
Bjerve et al., 1993 |
Case-control |
Cases = adults (n=156) Controls = normal human serum stored at −80 degrees C Aged >40 years Nord-Trondelag, Norway Previously undiagnosed diabetic patients Preterm infants (n=21) Very low birth weight, with birth weight <1500 g seen consecutively at the Department of Pediatrics |
Seafood and dietary DHA and AA intake |
10 weeks for adults and 1 year for the preterms |
|
Amount |
Results |
Conclusion* |
|
|
“Postnatal brain growth, expressed as wet weight of brain tissue, increased during the postpartum period, but was not as rapid as intrauterine brain growth.” “In contrast to the fatty acid components, postpartum levels of LA increased 4-fold relative to prenatal levels; postpartum brain levels of AA do not differ from those observed in brain during the third trimester.” “Chain elongation-desaturation of AA and LA to longer-chain homologues does not occur at maximal rates for several weeks postnatally or, alternatively, that these long-chain homologues if synthesized in extracerebral tissues may not be directed into synthesis of brain tissue during this early period of infant development.” |
N/A |
|
Number of fish meals per week: <2, 2, 3, and ≥4 Mean AA intake of these groups: (g/day) 1.22, 1.19, 1.31, 1.59 |
“After controlling for age, gender, BMI, alcohol intake, and smoking, there was a statistically significant positive correlation based on individual observations between increasing number of fish meals and the concentration of plasma phospholipid EPA (p<0.001) and DHA (p<0.001).” After controlling for APGAR score and weight at 1 year, 82% of the variance in MDI was explained by a model including the inverse of both DHA and EPA (p=0.0001). After controlling for weight at 1 year, 64% of the variance in PDI was explained by a model including the inverse of DHA (p=0.0001). |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Uauy et al., 1990 |
Case-control |
Case = infants fed formula by day 10 (n=32) Control = infants fed their own mother’s milk from birth (n=10) Birth weight appropriate for gestational age, able to receive enteral feedings, free of major neonatal morbidity by day 10 |
Human milk and milk formula |
Day 10 until 36 weeks old |
|
Makrides et al., 1994 |
Cross-sectional |
Male infants (n=16) Female infants (n=19) Died between weeks 2 and 48 South Australia All but two born at term |
Human milk and milk formula |
Within 48 weeks of birth |
|
Amount |
Results |
Conclusion* |
|
Human milk: 12.7 g/100 g AA, 1.5 g/100 g n-6 > C18, 0.8 g/100 g ALA, 0.5 g/100 g n-3>C18 Formula A: 24.2 g/100 g AA, 0.0 g/100 g n-6 > C18, 0.5 g/100 g ALA, 0.0 g/100 g n-3>C18 Formula B: 20.8 g/100 g AA, 0.0 g/100 g n-6 > C18, 2.7 g/100 g ALA, 0.0 g/100 g n-3>C18 Formula C: 20.4 g/100 g AA, 0.1 g/100 g n-6 > C18, 1.4 g/100 g ALA, 1.0 g/100 g n-3>C18 |
“Group C was comparable to the human milk-fed group, but Group A had lower DHA and n-3 LCPUFA in plasma and RBC membranes.” “Cone function was not affected by dietary essential fatty acids.” “Rod electroretinogram thresholds were significantly higher for Group A relative to the human milk-fed infants and Group C and significantly correlated with RBC n-3 LCPUFA (p<0.0001).” “Rod electroretinogram amplitude was significantly lower for Group A relative to the human milk-fed infants and Group C and related to plasma DHA and total n-3 LCPUFA (p<0.0001).” |
N/A |
|
Breast-feeding index = length of breastfeeding as a % of age at death: Breast-fed: ≥85% Formula fed: <30% LA in formula ranged from 12.0% to 15.0% and ALA in formula ranged from 1.0% to 1.6% |
Erythrocyte fatty acid composition of tissues were significantly lower in total saturated fatty acids (p<0.05), AA (p<0.05), and DHA (p<0.05) and significantly higher in DGLA (p<0.05), EPA (p<0.05), and DPA (p<0.05) for infants fed formula compared to those fed from the breast. Cortex fatty acid composition of tissues were significantly higher in 22:4n-6 (p<0.05), 22:5n-6 (p<0.05), and total n-6 (p<0.005) and lower in DHA (p<0.005) and total n-3 (p<0.005) for infants fed formula compared to those fed from the breast. There were no significant differences in retina fatty acid composition of tissues between the formula-fed and breast-fed infants. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Farquharson et al., 1992 |
Cross-sectional |
Term infants (n=20) Preterm infants (n=2) Greater Glasgow Health Board area Died within 43 weeks of birth Previously well infants who died suddenly in the home, “cot deaths” |
Human milk and milk formula |
Within 43 weeks of birth |
|
Martinez, 1992 |
Cross-sectional |
Infants born at different gestational ages and died soon after birth of acute causes that were not related to the central nervous system Not fed but mothers well-nourished Infants nourished in utero and after birth |
PUFA supplementation and PUFA-enriched formula |
After infant died (they died shortly after birth) |
|
Amount |
Results |
Conclusion* |
|
Breast milk or the formula milks SMA Gold Cap and/or White Cap, Cow and Gate Premium, or Osterfeed |
“Breast fed infants had greater concentrations of DHA in their cerebral cortex phospholipids than either the mixed fed group or the older SMA and CGOST groups.” “No significant differences in phospholipid fatty acid content of cerebral cortex were found between the age-comparable SMA and CGOST groups.” |
N/A |
|
Prenatal fatty acid amounts not specified |
“Long-chain fatty acids accumulate in the human brain during the brain’s growth spurt unless a serious imbalance in the supply of LA and ALA occurs.” “The active formation of synaptic structures and dendritic arborizations increases significantly between 31 weeks of gestation and term.” “It seems highly desirable to enrich parenteral lipids and milk formulas with DHA to provide between 0.5% and 1% of total fatty acids similar to those in human milk.” “A total n-6/n-3 fatty acid ratio between 5 and 7 seems appropriate according to our analysis of human milk from others consuming complete, balanced Mediterranean diets rich in fish.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Kodas et al., 2004 |
Animal |
2 generations of female Wistar rats |
ALA-deficient diet |
Control group: Control diet at birth to 60 days after birth Deficient group: Deficient diet at birth to 60 days after birth Diet reversed group 1: Control diet at day of birth until 60 days after birth Diet reversed group 2: Deficient diet until day 7 of life and then control diet from day 7 to day 60 of life Diet reversed group 3: Deficient diet until day 14 of life and then control diet from day 14 to day 60 of life Diet reversed group 4: Deficient diet until day 21 of life and then control diet from day 21 to day 60 of life |
|
Amount |
Results |
Conclusion* |
|
ALA-deficient diet: 6% fat African peanut oil <6 mg ALA/100 g diet 1200 mg LA/100 g diet Control diet: 60% peanut oil, 40% rapeseed oil 200 mg ALA/100 g diet 1200 mg LA/100 g diet |
The fatty acid composition of phosphatidylcholine in the hippocampus of 2-month-old rats was as follows: AA was not significantly different among the different diet groups; DHA was significantly higher in the control group and all diet reversed groups compared to the deficient group (p<0.05); n-6:n-3 was significantly lower in the control group and all diet reversed groups compared to the deficient group (p<0.05); these differences were not significant between the control group and the diet reversed groups. The fatty acid composition of phosphatidylethanolamine in the hippocampus of 2-month-old rats was as follows: AA was significantly lower in the control group and all diet reversed groups compared to the deficient group (p<0.05); DHA was significantly higher in the control group and all diet reversed groups compared to the deficient group (p<0.05); n-6:n-3 was significantly lower in the control group and all diet reversed groups compared to the deficient group (p<0.05); these differences were not significant between the control group and the diet reversed groups. The fatty acid composition of phosphatidylserine in the hippocampus of 2-month-old rats was as follows: AA was not significantly different among the different diet groups; DHA was significantly higher in the control group and all diet reversed groups compared to the deficient group (p<0.05); n-6:n-3 was significantly lower in the control group and all diet reversed groups compared to the deficient group (p<0.05); these differences were not significant between the control group and the diet reversed groups; and Basal 5-HT levels were significantly higher in the deficient group compared with the control group (p<0.05); there were no significant differences in basal 5-HT levels between the diet reversed groups 1, 2, and 3 and the control group; there were no significant differences in basal 5-HT levels between the diet reversed group 4 and the control group, deficient group, and all other diet reversed groups. |
B |
|
Amount |
Results |
Conclusion* |
|
n-6:n-3 diet (in mol%): 7.0% soybean oil 56.0% LA, 6.2% ALA, 9.0% n-6:n-3 n-3 diet (in mol%): 7.0% linseed oil 14.0% LA, 33.0% ALA, 0.4% n-6:n-3 n-6 diet (in mol%): 7.0% sunflower oil 65.0% LA, 0.3% ALA, 216.0% n-6:n-3 |
In the pups not exposed to ovalbumin: Delayed-type hypersensitivity responses against ovalbumin, as well as against human serum ovalbumin were not significantly different between the dietary groups; IgG anti-avalbumin and IgG anti-human serum ovalbumin antibodies were not significant different between the three diet groups; IgM anti-ovalbumin antibodies in the n-3 diet group are significantly higher than those in the n-6:n-3 diet group (p<0.05); and IgM anti-human serum ovalbumin antibodies in the n-3 diet group are significantly higher that those in the n-6: n-3 diet group (p<0.05). In the pups exposed to ovalbumin: Delayed-hypersensitivity responses against ovalbumin were significantly higher in the n-6:n-3 diet group compared to the n-3 diet group and the n-6 diet group, while delayed-hypersensitivity responses to human serum ovalbumin were significantly higher in the n-6:n-3 diet group compared to the n-3 diet group (p<0.05); IgG anti-human serum ovalbumin antibodies were significantly higher in the n-6:n-3 diet group than those in the n-3 diet group (p<0.05); and IgM anti-human serum ovalbumin antibodies in the n-3 diet group are significantly lower than those in the n-6: n-3 diet group and the n-6 diet group (p<0.05). Those in the n-3 diet group exposed to ovalbumin have significantly lower IgG ovalbumin, IgG anti-human serum ovalbumin, IgM anti-ovalbumin, and IgM anti-human serum ovalbumin antibodies than those not exposed to ovalbumin (p<0.05). Those in the n-6 diet group exposed to ovalbumin have significantly lower IgG ovalbumin and IgM anti-ovalbumin antibodies than those not exposed to ovalbumin (p<0.05). |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Levant et al., 2004 |
Animal |
Adult female Long-Evans rats |
LCPUFA-deficient diet |
Control diet: Day 1 of pregnancy until end of study Deficient diet: Day 1 of pregnancy until postnatal day 21. Postnatal day 21, half on deficient diet were changed to remediation diet and half stayed on deficient diet |
|
Amount |
Results |
Conclusion* |
|
Control diet: 0.35 kg/5 kg diet from soybean oil; no detected AA, EPA, DPA, or DHA Deficient diet: 0.35 kg/5 kg diet from sunflower oil; no detected AA, EPA, DPA, or DHA Remediation diet: 0.3275 kg/5 kg diet from sunflower oil and 0.0225 kg/5 kg diet from fish oil 0.1 g/100 g fatty acids AA, 1.6 g/100 g fatty acids EPA, 0.4 g/100 g fatty acids DPA, 3.5 g/100 g fatty acids DHA |
“Rats raised on the deficient diet exhibited a decrease in brain DHA content to 80% of control animals at maturity (p<0.05)” and an “increase in DPA content to 575% of control animals at maturity (p<0.001).” The remediation diet restored brain DHA and DPA content to levels similar to those on the control diet. Catalepsy score was significantly lower in the deficient diet group compared to the control group (p<0.05) and the remediation diet group (p<0.05). In a test of locomotor activity in a novel environment, the deficient diet group exhibited 187% of the activity of the control diet group during the 2-hour observation (p<0.05); results were similar between the deficient diet group and the remediation diet group. In the test of amphetamine-stimulated locomotor activity, the deficient diet group exhibited 144% of the activity of the control group (p<0.05). |
A |
|
Amount |
Results |
Conclusion* |
|
Semipurified diet: Deficient in n-3 fatty acids Safflower oil was sole fat source High n-6:n-3 ratio Controls: Soybean oil was sole fat source High in LA |
At all ages, animals of the “deficient group had considerably lower levels of n-3 fatty acids in tissue phospholipids than their controls.” Based on the occipital cortex, perinatal 22:5n-6 (p<0.01) and total n-6 (p<0.05) were significantly higher and perinatal DHA (p<0.01) and total n-3 (p<0.01) were significantly lower in the deficient group compared to the control group. Based on the occipital cortex, 22:4n-6 (p<0.01), 22:5n-6 (p<0.01), and total n-6 (p<0.01) at 22 months were significantly higher and DHA (p<0.01) and total n-3 (p<0.01) at 22 months were significantly lower in the deficient group compared to the control group. Based on the frontal cortex, perinatal 22:5n-6 (p<0.01) was significantly higher and perinatal DHA (p<0.01) and total n-3 (p<0.01) were significantly lower in the deficient group compared to the control group. Based on the frontal cortex, 22:5n-6 (p<0.01) and total n-6 (p<0.01) at 22 months were significant higher and DHA (p<0.01) and total n-3 (p<0.01) at 22 months were significantly lower in the deficient group compared to the control group. |
N/A |
TABLE B-1e Studies on Allergies: Effects on Infants and Children of Mothers Who Increase Seafood and/or Omega-3 Fatty Acid Intake
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Denburg et al., 2005 |
Randomized Controlled Trial |
Pregnant women (n=83) Booked for delivery at St. John of God Hospital Subiaco, Western Australia With confirmed allergy No smoking, other medical problems, complicated pregnancies, seafood allergy; normal dietary intake did not exceed two meals of fish per week |
Fish-oil supplement |
20 weeks of pregnancy until delivery |
|
Amount |
Results |
Conclusion* |
|
Fish oil group: 3.7 g of n-3 PUFA 56.0% as DHA and 27.7% as EPA Placebo group: 2.6 g olive oil 26 g/day oleic acid |
Infants of those in the fish oil group had a significantly higher %CD34 expression than infants of those in the placebo group (p<0.002). There was no significant difference between the two groups with respect to expression of all cytokine and chemokine receptors. There was a significant association found between CD34+ in cord blood and AEDS (OR=3.93; 95% CI 1.05-14.64, p=0.042) at one year of age; however, there were no significant associations found for food allergy, moderate severe AEDS, asthma, chronic cough, or recurrent wheeze. There were significant associations found between cord blood progenitor responsiveness to IL-5 and AEDS (OR=1.09, 95% CI 1.00-1.18, p=0.039) and recurrent wheeze (OR=1.11, 95% CI 1.02-1.21, p=0.022) at one year of age; however, there were no significant associations found for food allergy, moderate severe AEDS, asthma, or chronic cough. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Dunstan et al., 2003a |
Randomized Controlled Trial |
Pregnant women (n=83) Atopic women Booked for delivery at St. John of God Hospital Subiaco, Western Australia Physician-diagnosed allergic rhinitis and/or asthma Allergic to house dust mites, grass pollens, molds, cat, dog, feathers, and cockroach and/or asthma No medical problems, no smoking, no complicated pregnancies, no seafood allergy; normal diet did not exceed two meals of fish per week |
Fish-oil supplement |
20 weeks of pregnancy until delivery |
|
Dunstan et al., 2003b |
Randomized Controlled Trial |
Pregnant women (n=83) Atopic women Booked for delivery at St. John of God Hospital Subiaco, Western Australia Physician-diagnosed allergic rhinitis and/or asthma Allergic to house dust mites, grasses, molds, cat, dog, feathers, and cockroach and/or asthma No medical problems, no smoking, no complicated pregnancies, no seafood allergy; normal diet did not exceed two meals of fish per week; no preterm deliveries |
Fish-oil supplement |
20 weeks of pregnancy until delivery |
|
Amount |
Results |
Conclusion* |
|
Fish oil group: Four 1 g fish oil capsules/day 3.7 g of n-3 PUFA 56.0% as DHA and 27.7% as EPA Placebo group: Four 1 g olive oil capsules/day 66.6% n-9 oleic acid and <1.0% n-3 PUFA |
Neonatal in vitro IL-10 response to cat allergen was significantly lower in the fish oil group than in the placebo group (p=0.046). At birth, no significant differences were found in the neonates’ cytokine response to allergens and mitogens in the two groups at birth. IFN-γ responses to OVA were detected more frequently in the control group than in the fish oil group (p=0.009). There were no significant differences found in the frequency of detectable IL-5, IL-10, or IL-13 responses between the two groups. “The detection of a lymphoproliferative response to allergens also tended to be lower in the fish oil group compared with the control group,” although this difference was not always significant (OR=4.48, 95% CI 0.87-23.07 for response to OVA allergen and OR=2.02, 95% CI 0.69-5.88 for response to cat). |
B |
|
Fish oil group: Four 1 g fish oil capsules/day 3.7 g of n-3 PUFA 56.0% as DHA and 27.7% as EPA Placebo group: Four 1 g olive oil capsules/day 66.6% n-9 oleic acid and <1.0% n-3 PUFA |
IL-13 levels were significantly lower (p=0.025) in neonates whose mothers received fish-oil supplements in pregnancy compared to the placebo group. There were no significant differences in IFN-γ levels in cord plasmas or in IgE in plasma between the two groups. There were no significant differences in the frequency of lymphocyte subsets for total T cells, T helper cells, T suppressor cells, NK cells, and B cells between the two groups. After adjusting for parity, gender, and delivery method, there were significant associations between cord plasma IL-13 levels and neonatal red cell membrane DHA levels (β=−0.25, 95% CI −0.49 to −0.01) and total n-3 fatty acid levels (β=−2.70, 95% CI −5.35 to −0.05). |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Hawkes et al., 2002 |
Randomized Controlled Trial |
Women (n=120) Aged 20-42 years, mean about 30 years Delivered full-term singleton infants, intended to breast-feed ≥12 weeks Adelaide, South Australia No known history of inflammatory disorders, not currently taking anti-inflammatory medication or fish-oil supplements Excluded women who had ceased lactating by 4 weeks postpartum |
DHA supplement |
Day 3-week 12 postpartum |
|
Amount |
Results |
Conclusion* |
|
Asked to limit fish and seafood intake to a maximum of 1 meal/week Placebo: 500 mg placebo oil Low-DHA capsule group: 70 mg EPA/day, 300 mg DHA/day High-DHA capsule group: 140 mg EPA/day, 600 mg DHA/day |
“There was no significant difference between the dietary groups in mean rank concentrations of IL-6 or TNF-α in the aqueous phase of milk” at 4 weeks postpartum. “There was no significant difference in mean rank concentrations between the dietary groups for any of the cytokines produced by cells isolated from human milk or peripheral blood after in vitro stimulation with lipopolysaccharide or in the absence of stimulation” at 4 weeks postpartum. |
N |
|
Amount |
Results |
Conclusion* |
|
Omega-3 diet group: Canola oil and canola-based margarines and salad dressings to replace usual oils and margarines Supplement capsules = 0.18 g EPA and 0.12 g DHA/capsule 4 capsules/day = 1.20 g omega-3/day Omega-6 diet group: Sunflower oil and sunflower oil-based margarines and salad dressings to replace usual oils and margarines Supplement capsules = 0.45 g safflower oil, 0.45 g palm oil, 0.10 g olive oil/capsule No EPA or DHA |
“There was no significant change in spirometric function, dose-response ratio to histamine or asthma severity score at either 3 or 6 months in either group.” |
N |
|
Amount |
Results |
Conclusion* |
|
Cord blood (percentages of total red blood cell membrane phospholipid): Medians: 0.02 ALA, 0.11 EPA, 0.22 DPA, 2.00 DHA, 4.65 LA, and 7.80 AA Maternal blood (percentages of total red blood cell membrane phospholipid): Medians: 0.14 ALA, 0.23 EPA, 0.60 DPA, 2.02 DHA, 11.46 LA, and 5.88 AA |
After controlling for sex, gestational age at birth, birth weight, mother’s age, education level, housing tenure, parity, ethnicity, smoking in pregnancy, maternal atopic disease, child’s head circumference at birth, child’s crown to heel length at birth, mother’s BMI, breastfeeding in first 6 months, and day care use in first 6 months: All associations between fatty acid exposure (based on cord blood levels and maternal blood levels) and eczema at 18 to 30 months were found to be nonsignificant; All associations between fatty acid exposure (based on both cord blood levels and maternal blood levels) and wheezing at 30 to 42 months of age were found to be nonsignificant; LA:ALA levels in cord blood were significantly associated with later-onset wheeze (OR=1.30, 95% CI 1.04-1.61), as was the ratio of ALA:sum of n-3 products (OR=0.86, 95% CI 0.75-0.99); and No other significant associations were found between fatty acid exposure and transient infant wheeze, later-onset wheeze, or persistent wheeze. |
N |
TABLE B-1f Studies on Visual Acuity: Effects on Infants Supplemented with Omega-3 Fatty Acids in Formula
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Simmer, 2005 |
Cochrane Review |
9 Randomized Controlled Trials |
LCPUFA-supplemented formula |
|
|
Gibson et al., 2001 |
Review |
Randomized Controlled Trials (11 on preterm and 10 on term infants) Involving healthy preterm infants fed preterm formula Involving healthy term infants fed formulas from near birth Systematic literature review |
DHA-supplemented formula |
|
|
Uauy et al., 2001 |
Review |
Summary of Randomized Controlled Trials on preterm and term infants |
LCPUFA-supplemented formula |
|
|
Amount |
Results |
Conclusion* |
|
|
“There is little evidence from randomized trials of LCPUFA supplementation to support the hypothesis that LCPUFA supplementation confers a benefit for visual or general development of term infants.” “Minor effects on VEP acuity have been suggested, but appear unlikely when all studies are reviewed.” |
N |
|
|
“Benefits of adding DHA to formulas (with or without AA) on VEP acuity have been reported in some studies, whereas other studies have failed to detect a benefit of LC-PUFA supplementation.” |
B |
|
|
There is evidence supporting “the view that dietary essential fatty acid supply affects visual development of preterm and term infants.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
SanGiovanni et al., 2000a |
Meta-analysis |
Studies done in industrialized countries Healthy, term infants Randomized studies: DHA supplemented (n=114) DHA-free (n=87) Nonrandomized studies: Milk-fed/behavioral-based (n=117 at 2 months; n=148 at 4 months) Milk-fed/electrophysiological tasks (n=146 at 4 months) DHA-free/behavioral-based (n=174 at 2 months; n=113 at 4 months) DHA-free/electrophysiological tasks (n=108 at 4 months) All study designs: DHA-supplemented/behavioral-based at 2 months (n=219) DHA-supplemented/electrophysiological tasks at 4 months (n=265) DHA-free/behavioral-based at 2 months (n=86) DHA-free/electrophysiological tasks at 4 months (n=109) |
DHA-supplemented formula |
|
|
Amount |
Results |
Conclusion* |
|
|
Based on behavioral tests of visual acuity, the randomized studies showed a significant difference in the estimates for those fed DHA-supplemented formula vs. those fed unsupplemented formula at 2 months of age (p≤0.0005). This difference was not significant at any other age presented. Based on behavioral tests of visual acuity, the non-randomized studies showed a significant difference in the estimates for those fed human milk vs. those fed unsupplemented formula at 2 months of age (p≤0.0005) and 4 months of age (p≤0.05). This difference was not significant at any other age presented. Based on electrophysiological tests of visual acuity, the randomized studies showed a significant difference in the estimates for those fed (DHA-supplemented) formula vs. those fed unsupplemented formula at 7 months of age (p≤0.05). This difference was not significant at any other age presented. Based on electrophysiological tests of visual acuity, the nonrandomized studies showed a significant difference in the estimates for those fed human milk vs. those fed unsupplemented formula at 4 months of age (p≤0.0005), 5 months of age (p≤0.05), and 7 months of age (p≤0.05). This difference was not significant at any other age presented. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
SanGiovanni et al., 2000b |
Meta-analysis |
5 original papers (4 prospective trials) 4 review chapters Preterm infants Randomized studies: DHA-supplemented/behavioral-based (n=48 at 2 months; n=70 at 4 months) DHA-supplemented/VEP at 4 months (n=13) DHA-free/behavioral-based (n=49 at 2 months; n=56 at 4 months) DHA-free/VEP at 4 months (n=28) All study designs: DHA-supplemented/behavioral-based at 4 months (n=80) DHA-supplemented/VEP at 4 months (n=37) DHA-free/behavioral-based at 4 months (n=87) DHA-free/VEP at 4 months (n=43) |
DHA-supplemented formula |
|
|
Amount |
Results |
Conclusion* |
|
|
Based on behavioral tests of visual acuity, the randomized comparisons (between those fed DHA-supplemented formula and those fed unsupplemented formula) showed significant differences at 2 and 4 months of age (p≤0.001). This difference was not significant at any other age presented. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Hoffman et al., 2003 |
Randomized Controlled Trial |
Infants (n=61) Healthy, term, singleton infants Birth weight appropriate for gestational age Breast-fed to 4-6 months North Dallas area, TX 95% White No family history of milk protein allergy; genetic or familial eye disease; vegetarian or vegan maternal dietary patterns; maternal metabolic disease, anemia, or infection; presence of a congenital malformation or infection; jaundice; perinatal asphyxia; meconium aspiration; or any perinatal event that resulted in placement in the neonatal intensive care unit |
AA/DHA-supplemented formula |
Enrolled at 6.5 weeks of age until 12 months of age (during time of weaning) |
|
Amount |
Results |
Conclusion* |
|
Commercial formula (Enfamil with iron) or commercial formula supplemented with 0.36% of total fatty acids as DHA and 0.72% as AA |
There were no significant differences in VEP acuity before weaning in the two groups, but at 12 months the supplemented group had significantly better VEP acuity than infants in the commercial formula group (p<0.0005). There was a trend of better stereoacuity in the supplemented group compared to the commercial group at 9 months (p=0.12) and 12 months (p=0.13). |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Birch et al., 2002 |
Randomized Controlled Trial |
Infants (n=65) Healthy, term, singleton births Birth weight appropriate for gestational age Weaned from breastfeeding at 6 weeks of age Dallas area, TX Mean maternal age about 30 years 75-78% White Majority of mothers with at least a college degree No family history of milk protein allergy; genetic or familial eye disease; vegetarian or vegan maternal dietary patterns; maternal metabolic disease, anemia, or infection; presence of a congenital malformation or infection; jaundice; perinatal asphyxia; meconium aspiration; or any perinatal event that resulted in placement in the neonatal intensive care unit |
AA/DHA-supplemented formula |
6 weeks of age to 52 weeks of age |
|
Amount |
Results |
Conclusion* |
|
Commercial formula (Enfamil with iron) or commercial formula supplemented with 0.36% of total fatty acids as DHA and 0.72% as AA |
There were no significant differences in VEP acuity at age 6 weeks between the two groups. The control group had significantly poorer visual acuity at week 17 (p<0.003), week 26 (p<0.001), and week 52 (p<0.001) compared to the supplemented group. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Innis et al., 2002 |
Randomized Controlled Trial |
Infants (n=194) Premature Healthy, very low birth weight infants (846-1560 g), formula-fed Multi-center study (16 neonatal centers in North America) Not small for gestational age or >24 days postnatal age when full enteral feeds ≥375 kJ/kg/day were achieved No necrotizing enterocolitis or other gastrointestinal disease, impaired visual or ocular status, or a history of underlying disease or congenital malformation that could interfere with growth Reference group = term infants whose mothers anticipated breastfeeding for at least 4 months |
AA/DHA-supplemented formula |
Preterm formulas: At least 28 days after enteral intake of 375 kJ/kg/day reached Term formulas: After hospital discharge until 57 weeks of age |
|
Amount |
Results |
Conclusion* |
|
Preterm formula 1 = Control formula (no AA or DHA) Preterm formula 2 = DHA formula (0.34% fatty acids as DHA) Preterm formula 3 = DHA+AA formula (0.33% fatty acids as DHA, 0.60% fatty acids as AA) Term formula = no AA or DHA Breast-fed term infants = no solid foods during the study unless otherwise instructed by their physicians |
At 57 weeks, visual acuity of the breast-fed term infants was significantly higher than in the premature infants, but not at 48 weeks; at 48 or 57 weeks, visual acuity was not significantly different among the premature infant groups. |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Van Wezel-Meijler et al., 2002 |
Randomized Controlled Trial |
Infants (n=42) Preterm, admitted to neonatal intensive- or high-care unit of hospital Birth weight <1750 g Leiden, Netherlands Mothers not breast-feeding Normal neurological examination throughout the neonatal period Repeated ultrasound of the brain being normal or showing, at most, minor abnormalities No abnormalities of the central nervous system; abnormal neurological examination or occurrence of seizures; any systemic disease with potential negative influence on future growth or development; serious nutritional or gastrointestinal problems preventing initiation of enteral feeding after the first week postpartum or complete enteral feeding after the third week postpartum; retinopathy of prematurity grade 3 or more |
AA/DHA-supplemented formula |
2-3 weeks after birth until weighing 3000 g |
|
Amount |
Results |
Conclusion* |
|
Supplemented preterm formula: 4.4 g fat/100 mL 0.015 g/100 mL of added DHA (microalgae) 0.031 g/100 mL of added AA (fungi) Control formula: 4.4 g fat/100 mL No addition of AA and DHA |
There were no significant differences found in Flash VEP at 3 and 12 months between the two groups. There were no significant differences found in visual acuity at 3, 6, 12, or 24 months between the two groups. |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Makrides et al., 2000 |
Randomized Controlled Trial |
Infants (n=73 in formula groups; n=63 in breastfed group) White Full-term and appropriate weight for gestational age Mean mothers’ education was mid-secondary school level for formula-fed infants and completion of secondary school for breastfed infants No congenital disease or complications during pregnancy |
AA/DHA-supplemented formula |
Age at entry not specified, up to 34 weeks of age |
|
Bougle et al., 1999 |
Randomized Controlled Trial |
Infants (n=40) Mean age about 33 weeks Enrolled the 2nd day of enteral feeding Healthy, appropriate weight for gestational age Premature Free of respiratory, metabolic or neurological disease; malformations; infections; intrauterine asphyxia Fed by digestive route within the first 7 days of life |
LCPUFA-supplemented formula |
Within the first 2 days of enteral feeding, then for 30 days |
|
Amount |
Results |
Conclusion* |
|
Placebo formula (% total fatty acids): 16.8% LA, 1.5% ALA DHA formula (% total fatty acids): 16.80% LA, 1.20% ALA, 0.10% EPA, 0.35% DHA DHA+AA formula (% total fatty acids): 16.60% LA, 0.34% AA, 1.00% ALA, 0.34% DHA Breast milk (% total fatty acids, mean±SE): 13.40±2.90% LA, 0.39±0.07% AA, 0.95±0.32% ALA, 0.09±0.03% EPA, 0.20±0.07% DHA |
After adjusting for gender, postconceptional age, birth weight, and maternal smoking, there were no significant differences in VEP between any of the groups at 16 or 34 weeks of age. |
N |
|
Breast milk (% total fatty acids, mean±SE): 14.1±2.0% LA, 0.4±0.2% GLA, 0.9±0.2% AA, 0.5±0.1% ALA, 0.5±0.1% DHA Formula A (% total fatty acids): 14.1% LA, 1.3% ALA Formula B (% total fatty acids): 17.7% LA, 0.4% GLA, 0.1% AA, 1.2% ALA, 0.1% EPA, 0.6% DHA |
There were no significant differences between the groups based on electrophysiological data, except that the maturation of the motor nerve conduction was significantly slower in the Formula B group than in the breast milk group and the Formula A group (p<0.05). |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Carlson et al., 1999 |
Randomized Controlled Trial |
Infants (n=119) |
AA/DHA-supplemented formula |
<8 days of age until about 12 months of age Infants fed supplemented formula near birth received commercial formula from term less 3 months until 12 months of age; infants fed supplemented formula near term received commercial formula from term less 3 months to term less 1 month, and then supplemented formula until 12 months of age |
|
Amount |
Results |
Conclusion* |
|
Commercially available standard formula contained no EPA or DHA Supplemented formula 0.13% DHA and 0.40% AA from egg phospholipids |
Compared to the infants not supplemented, “only those supplemented near birth had higher acuity at 2 months (p<0.02) and a trend toward higher acuity at 6 months (p<0.07).” Infants supplemented at birth “also had higher acuity than those supplemented at term at 2 months (p<0.05).” “First year acuity continued to increase (p<0.05) between consecutive ages until 6 months” in those supplemented at birth and 9 months in those unsupplemented and supplemented at term. “All groups had similar acuity at 9 and 12 months.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Birch et al., 1998 |
Randomized Controlled Trial |
Infants (n=108) Healthy, term, birth weight appropriate for gestational age Singleton births Dallas, TX 75% White, 12% Black, 12% Hispanic, 1% other Mean maternal age 29 years 67.6% mothers completed at least 2 years of college No family history of milk protein allergy; genetic or familial eye disease; vegetarian or vegan maternal dietary patterns; maternal metabolic disease, anemia, or infection; presence of a congenital malformation or infection; jaundice; perinatal asphyxia; meconium aspiration; or any perinatal event that resulted in placement in the neonatal intensive care unit |
AA/DHA-enriched formula |
0-4 days postpartum through 17 weeks of age |
|
Carlson et al., 1996a |
Randomized Controlled Trial |
Infants (n=58) Born at term (37-43 weeks) Birth weight 747-1275 g Memphis, TN Predominantly Black No growth retardation in utero and no medical problems likely to influence long-term growth and development Mothers education mean of about 12 years |
DHA-supplemented formula |
24 hours after birth; end point not specified |
|
Amount |
Results |
Conclusion* |
|
Enfamil + iron Enfamil + iron + 0.35% DHA Enfamil + iron + 0.36% DHA + 0.72% AA |
Visual acuity was significantly poorer in the control group than in the DHA or DHA+AA groups and the breast-fed group. At 6, 17, 26, and 52 weeks the association between RBC AA and sweep VEP was not statistically significant. The association was also nonsignificant for RBC EPA. At 6, 17, 26, and 52 weeks, the association between RBC DHA was significantly associated with lower sweep VEP (p<0.001, p=0.01, p=0.05, p<0.001, respectively). At 6, 17, and 52 weeks, the association between RBC n-3:n-6 was significantly associated with lower sweep VEP (p<0.001, p=0.03, p<0.001, respectively); the association was not statistically significant at 26 weeks. |
B |
|
Formula with AA+DHA = 2 g AA/100 g total fatty acids; 0.1 g DHA/100 g total fatty acids Formula without DHA = 2.2 g ALA/100 g total fatty acids |
“Term infants fed formulas with added AA and DHA had higher grating acuity at 2 months of age but not at 4, 6, 9, or 12 months of age compared with infants fed an unsupplemented formula.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Carlson et al., 1996b |
Randomized Controlled Trial |
Infants (n=59) Memphis, TN Maternal mean age about 22.5 year No intraventricular or periventricular hemorrhage > grade 2; a history of maternal cocaine or alcohol abuse; congenital anomalies likely to affect long-term growth and development; or intrauterine growth retardation Full enteral feeding of 418 kJ/kg/day by 6 weeks of age and tolerated enteral feeding thereafter |
EPA/DHA-supplemented formula (marine oil) |
Between 3-5 days postpartum until 2 months from expected term of 48±1 week post-menstrual age |
|
Carlson et al., 1993 |
Randomized Controlled Trial |
Infants (n=67) Birth weight 748-1398 g Mean gestational age 29 weeks Memphis, TN Did not require mechanical ventilation; have intraventricular hemorrhage > grade 2; have retinopathy of prematurity > stage 2; require surgical intervention for necrotizing enterocolitis; have severe intrauterine growth retardation; or a history of maternal substance abuse Predominantly Black and from lower socioeconomic groups Maternal age about 23 years |
EPA/DHA-supplemented formula (marine oil) |
Preterm formula from when infant tolerated enteral intakes >462 kJ/kg body weight/day for 5-7 days (≈3 weeks of age) until discharge Term formula from discharge until 9 months |
|
Amount |
Results |
Conclusion* |
|
Standard preterm formula = LA at 2.5% of total fatty acid Marine-oil supplemented formula = 0.20% DHA and 0.06% EPA of total fatty acids |
“Visual acuity improved significantly between successive ages of 0 and 2 months, 2 and 4 months … Between 6 and 12 months visual acuity plateaued.” |
B |
|
Commercially available standard formula contained no EPA or DHA Marine-oil supplemented formula contained 0.2% DHA and 0.3% EPA of total fatty acids |
Visual acuity development was significantly higher in the marine-oil group compared to the control group at 2 months (p<0.014) and 4 months (p<0.002). There were no significant differences found at the other ages reported. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Birch et al., 1992 |
Randomized Controlled Trial |
Male infants (n=32) Female infants (n=41) Born 27-33 weeks gestation Birth weight 1000-1500 g No respirator treatment for more than 7 days or congenital infections; gross congenital malformations; retinopathy of prematurity; or grade III or IV intracranial hemorrhages |
EPA/DHA-supplemented formula (soy/ marine oil) |
10 days of age until 6 months of age |
|
Lauritzen et al., 2001 |
Review |
Summary of the literature (animal, observational, RCTs) |
DHA-supplemented formula |
|
|
Amount |
Results |
Conclusion* |
|
Soy/marine oil-supplemented formula (preterm/follow-up formula, g/100 g lipids): LA = 20.4/18.1 ALA = 1.4/1.4 EPA+DHA = 1.0/0.9 Corn oil-based formula (preterm/follow-up formula, g/100 g lipids): LA = 24.2/21.1 ALA = 0.5/0.5 EPA+DHA = 0.0/0.0 Soy oil-based formula (preterm/follow-up formula, g/100 g lipids): LA = 20.8/20.3 ALA = 2.7/2.8 EPA+DHA = 0.0/0.1 |
There were significant differences in VEP acuity for the different formula groups (p<0.025), with the corn oil group having poorer VEP acuity than the soy/marine oil group (p<0.05) at 36 weeks. The corn oil group (p<0.05) and the soy oil group (p<0.05) had significantly poorer VEP acuity than the soy/marine oil group at 57 weeks. |
B |
|
|
“Observational studies in general show better retinal function in breast-fed infants than in infants fed formula without DHA, but approximately half of the intervention studies show no effect.” Animal studies do offer evidence that DHA plays a role in retinal function, but these results cannot easily be extrapolated to humans. 4 RCTs with “preterm infants have all shown a positive effect of dietary DHA on visual development;” the results from term infants are not as conclusive. More data is needed to see if the “variation in DHA content of human milk has a functional effect.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Williams et al., 2001 |
Cohort |
Boys and girls (n=435) Mean age of 3.5 years Born in last 6 months of the Avon Longitudinal Study of Parents and Children (ALSPAC) enrollment period Healthy term infants |
Seafood (mother) and breast milk (child) |
Seafood = during pregnancy (mother) Breast milk = until 4 months of age (child) |
|
Amount |
Results |
Conclusion* |
|
Oily fish consumption categories: 1 = Never or rarely 2 = Once every 2 weeks 3 = More than once every 2 weeks White fish = cod, haddock, plaice, and “fish fingers” Oily fish = pilchards, sardines, mackerel, tuna, herring, kippers, trout, and salmon |
After adjusting for breast-feeding, sex, maternal education, maternal age, housing tenure, financial difficulties, maternal smoking, number of older siblings in household, child care, maternal job status, mother being vegetarian, mother’s fish-eating habits: “Mothers who ate oily fish at least once every 2 weeks during pregnancy were more likely to have children who achieved foveal stereoacuity than were the mothers who never ate oily fish (OR=1.57, 95% CI 1.00-2.45),” but this was not significant; and “The results of this study suggest that for full-term infants, breast-feeding is associated with enhanced stereopsis at age 3.5 years, as is a maternal DHA-rich antenatal diet, irrespective of later infant feeding practice.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Carlson et al., 1986 |
Cohort |
Infants (n=27) Born on or before 32 weeks gestation (range 24-32 weeks) University of Mississippi Medical Center Weighed <1500 g at birth and were on full feedings of at least 60 kcal/kg without intravenous supplementation Free of major congenital malformations and did not have any ongoing major disease process Discharged at about 1800 g |
Human milk and milk formula |
Delivery to an average of 7 weeks later |
|
Amount |
Results |
Conclusion* |
|
Expressed, previously frozen milk produced by their own mothers or formula Infants fed formula started with enteral feeding with Portagen and then Enfamil Premature and Similac Special Care as tolerated. Those followed after discharge were fed term formulas also produced by Enfamil and Similac Human milk (in mol%, mean±SE): LA = 16.00±1.30, AA = 0.59±0.04, ALA = 0.62±0.04, EPA = 0.03±0.00, DPA = 0.09±0.03, DHA = 0.19±0.03 Portagen (in mol%, mean±SE): LA = 8.1, AA = None, ALA = Trace, EPA = None, DPA = None, DHA = None Enfamil Premature (in mol%, mean±SE): LA = 22.4, AA = None, ALA = 0.6, EPA = None, DPA = None, DHA = None Similac Special Care (in mol%, mean±SE): LA = 17.4, AA = None, ALA = 0.9, EPA = None, DPA = None, DHA = None |
Based on phosphatidylethanolamine composition of fatty acids (in mol%): EPA was significantly lower (p<0.005) in those breast-fed after the feedings than in the pre-study samples; LA and DPA were significantly higher (p<0.001) and DHA was significantly lower (p<0.005) in those breast-fed after the feedings than in the preterm cord blood; LA was significantly higher (p<0.005) and EPA was significantly lower (p<0.005) in those formula-fed after the feedings than in the pre-study samples; LA was significantly higher (p<0.005) and DHA was significantly lower (p<0.001) in those formula-fed compared to those breast-fed; LA (p<0.005) and DPA (p<0.001) were significantly higher and AA (p<0.005) and DHA (p<0.001) were significantly lower in those formula-fed after the feedings than in the preterm cord blood; LA was significantly higher (p<0.005) and EPA was significantly lower (p<0.005) in those formula-fed after the feedings than in the pre-study samples. Based on phosphatidylcholine composition of fatty acids (in mol%): LA was significantly higher (p<0.005) in those breast-fed after the feedings than in the pre-study samples; LA was significantly higher (p<0.005) and AA (p<0.001) and DHA (p<0.005) were significantly lower in those breast-fed after the feedings than in the preterm cord blood; LA was significantly higher (p<0.001) and AA was significantly lower (p<0.001) in those formula-fed after the feedings than in the pre-study samples; LA was significantly higher (p<0.005) and AA and DHA were significantly lower (p<0.001) in those formula-fed compared to those breast-fed; LA was significantly higher (p<0.005) and AA and DHA were significantly lower (p<0.001) in those formula-fed after the feedings than in the preterm cord blood. Based on phosphatidylserine composition of fatty acids (in mol%): LA and DHA were significantly higher (p<0.005) in those breast-fed after the feedings than in the preterm cord blood; AA was significantly lower (p<0.005) in those breast-fed after the feedings than in the pre-study samples; LA and DHA were significantly higher (p<0.005) in those formula-fed after the feedings than in the pre-study samples; AA was significantly lower (p<0.005) and DHA was significantly higher (p<0.025) in those formula-fed after the feedings than in the pre-study samples. |
N/A |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Putnam et al., 1982 |
Cohort |
Infants (n=40) Enrolled at birth Well-baby clinic at the University of South Florida Medical Clinics At least 90% of energy from human milk or formula before sample collection |
Human milk and milk formula |
3 weeks of age to 6 months of age Breast milk collected at 8 weeks and infants’ blood drawn between 4.5 and 6 months of age |
|
Amount |
Results |
Conclusion* |
|
Mothers were encouraged to follow the recommendations of the American Academy of Pediatrics Committee on Nutrition (food other than human milk or humanized formula be omitted from infant’s diet until he/she was 4-6 months of age) Human milk (% of total, mean): 15.80±0.61 LA, 0.60±0.03 AA, 0.80±0.09 ALA, 0.10±0.03 EPA, 0.10±0.01 DPA, 0.10±0.01 DHA Enfamil + iron (% of total, mean): 45.1 LA, No AA, 5.0 ALA, No EPA, No DPA, No DHA SMA formula (% of total, mean): 14.0 LA, No AA, 1.2 ALA, No EPA, No DPA, No DHA |
“Human milk-fed infants had lower concentrations of membrane LA than SMA-fed infants despite the equivalent relative intakes of dietary LA.” “These diets did not influence the relative contributions of PE, PC, Sp, and PS to erythrocyte membrane phospholipid nor did they influence the lipid phosphorous/cholesterol ratio.” Significant differences in fatty acid composition of infant erythrocyte ethanolamine are as follows (weight % of total fatty acid methyl esters): Infants fed human milk had significantly higher AA (p<0.05), DPA (p<0.05), and DHA (p<0.001) than those fed SMA formula; and Infants fed human milk had significantly higher AA (p<0.01) and significantly lower LA (p<0.001), ALA (p<0.001), EPA (p<0.05), and DHA (p<0.001) than those fed Enfamil formula with iron. |
N/A |
|
Amount |
Results |
Conclusion* |
|
Breast milk (% total fatty acids, mean±SE): LA = 6.90±0.81, ALA = 0.80±0.05, EPA = 0.20±0.08, DPA = 0.52±0.27, DHA = 0.59±0.23 Milk formula (% total fatty acids, mean): LA = 1.60, ALA = 0.70, EPA = 0.08, DPA = 0.11, DHA = 0.02 |
LA, AA, DHA are significantly lower in the formula-fed infants than in the breast-fed infants (p<0.01, p<0.05, p<0.01, respectively). EPA and DPA are significantly higher in the formula-fed infants than in the breast-fed infants (p<0.05). “The minimum requirement of the young infant for LA is substantially less than 1% of the dietary energy, the value most widely quoted.” |
N/A |
|
Experimental group: Semipurified diet deficient in n-3 fatty acids Safflower oil sole fat source 76.0% LA, 0.3% GLA, 0.2% DGLA, 0.3% ALA, 225.0% n-6:n-3 of total fatty acids Control group: Soy bean oil sole fat source 53.1% LA, 0.0% GLA, 0.3% DGLA, 7.7% ALA, 7.0% n-6:n-3 of total fatty acids |
AA and total n-6 fatty acids were significantly higher in the experimental group infants compared to the control group infants (p<0.005). ALA, EPA, DPA, DHA and total n-3 fatty acids are all significantly lower in the experimental group infants compared to the control group infants (p<0.001). At 4, 8, and 12 weeks, the visual acuity threshold in the experimental group was significantly lower than in the control group (p<0.05, p<0.0005, p<0.005, respectively). |
B |
TABLE B-1g Studies on Cognitive and Motor Development: Effects on Infants Supplemented with Omega-3 Fatty Acids in Formula
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Cohen et al., 2005 |
Review |
Aggregated 8 randomized controlled trials (1 study of maternal dietary supplementation and 7 studies of formula supplementation) |
n-3 supplement |
|
|
Simmer and Patole, 2005 |
Cochrane Review |
11 randomized controlled trials |
LCPUFA-supplemented formula |
|
|
Simmer, 2005 |
Cochrane Review |
9 randomized controlled trials |
LCPUFA-supplemented formula |
|
|
Amount |
Results |
Conclusion* |
|
|
An increase in maternal intake of DHA during pregnancy of 1 g/day will increase child IQ by 0.8-1.8 points. “Prenatal maternal DHA intake increasing the child plasma (RBC) DHA phospholipid fraction by 1% has the same impact on cognitive development as formula DHA supplementation that increases the child’s plasma (RBC) DHA phospholipid fraction by 1%.” “Because typical DHA intake associated with fish consumption is well under 1 g/day, changes in fish consumption will result in IQ effects amounting to a fraction of a point,” but they are not clinically detectable. |
B |
|
|
“No long-term benefits were demonstrated for infants receiving formula supplemented with LCPUFA. There was no evidence that supplementation of formula with n-3 and n-6 LCPUFA impaired the growth of preterm infants.” |
N |
|
|
“There is little evidence from randomized trials of LCPUFA supplementation to support the hypothesis that LCPUFA supplementation confers a benefit for visual or general development of term infants.” “Minor effects on VEP acuity have been suggested, but appear unlikely when all studies are reviewed.” |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Gibson et al., 2001 |
Review |
Randomized controlled trials (11 on preterm and 10 on term infants) Involving healthy preterm infants fed preterm formula Involving healthy term infants fed formulas from near birth Systematic literature review |
LCPUFA-supplemented formula |
|
|
Uauy et al., 2001 |
Review |
Summary of randomized controlled trials on preterm and term infants |
AA/DHA-supplemented formula |
|
|
Carlson and Neuringer, 1999 |
Review |
Summary of animal studies and randomized controlled trials Based on a session from the AOCS 1996 meeting: PUFA in Infant Nutrition: Consensus and Controversies |
Neural DHA accumulation |
|
|
Amount |
Results |
Conclusion* |
|
|
“Although there are still some concerns on safety issues regarding the addition of LCPUFA to preterm infant formula, the evidence in support of a beneficial effect of such supplementation on visual function is relatively compelling.” “It seems that the possible negative effects of n-3 LCPUFA on growth of preterm infants have been overcome through improved study design and/or the addition of a balance of n-6 and n-3 LCPUFA.” “There is also mixed evidence for the support of an effect of dietary LCPUFA on more global measures of development (Bayley’s Scales of Infant Development or Brunet-Lezine test).” |
B |
|
|
“Evidence for a beneficial effect of AA+DHA supplementation on CNS development is strong.” “The preliminary information on cognitive development is insufficient to fully establish a relationship between LCPUFA and mental development.” |
B |
|
|
Studies in deficient monkeys suggest that “lower brain accumulation of DHA may influence neural domains such as sensation, motivation or temperament, but not cognition.” “The most consistent effect identified to date in human and animal studies has been that of look duration and tests of visual attention.” “A limited number of behavioral studies in animals and humans address the question of neural DHA accumulation and developmental measures other than vision.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Bouwstra et al., 2005 |
Randomized Controlled Trial |
Infants (n=256 to 446, depending on assessment) Term, healthy Groningen, Netherlands University and Martini Hospitals in Groningen and at midwife clinics No congenital disorders that interfered with adequate functioning in daily life; infants from multiple births; infants whose mothers did not have mastery of the Dutch language or suffered from significant illness or disability; adopted or foster infants; or formula-fed infants who had received human milk >5 days |
LCPUFA-supplemented formula |
Birth to 2 months of age |
|
Amount |
Results |
Conclusion* |
|
Control formula (in mol%): 11.56 LA, 1.27 ALA Supplemented formula (in mol%): 11.00 LA, 0.18 GLA, 0.03 DGLA, 0.39 AA, 1.30 ALA, 0.06 EPA, 0.23 DHA Breastfed (in mol%, mean±SE): 13.62±4.24 LA, 0.11±0.03 GLA, 0.34±0.06 DGLA, 0.34±0.06 AA, 1.11±0.35 ALA, 0.06±0.04 EPA, 0.19±0.11 DHA |
“The groups did not show statistically significant differences in clinical neurological condition, neurological optimality score, fluency score, and the psychomotor and mental development indices at 18 months.” |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Clandinin et al., 2005 |
Randomized Controlled Trial |
Infants (n=361) Preterm Multi-site study First phase: Gestational age ≤35 weeks postmenstrual age <10 total days of enteral feeding of >30 mL/kg/day No congenital abnormalities of the gastrointestinal tract, hepatitis, hepatic or biliary pathology, necrotizing enterocolitis confirmed before enrollment, or history of underlying disease or congenital malformations likely to interfere with evaluation Second phase: Successful completion of the first phase, ≥80% of enteral intake from study formula during hospitalization, and 100% caloric intake from study formula at completion of the first phase |
Algal-DHA- and fish-DHA-supplemented formulas, human milk |
Premature formula: ≥14 days of age until at/near hospital discharge (40 weeks of age) Discharge formula: 40 weeks until 53 weeks post-menstrual age Term formula: 53 weeks until 92 weeks post-menstrual age |
|
Amount |
Results |
Conclusion* |
|
Control formula: No DHA or AA Algal-DHA formula: 17 mg DHA/100 kcal from algal oil, 34 mg AA/100 kcal from fungal oil 0.3% fatty acids from DHA, 0.6% fatty acids from AA Fish-DHA formula: 17 mg DHA/100 kcal from tuna fish oil, 34 mg AA/100 kcal from fungal oil 0.3% fatty acids from DHA, 0.6% fatty acids from AA Worldwide human milk: 0.3% DHA and 0.6% AA (weight of fatty acids) |
At 118 weeks, breast-fed term infants had significantly higher MDI and PDI scores compared to the control formula group, the algal-DHA formula group, and the fish-DHA formula group (p<0.05). At 118 weeks, the algal-DHA formula group had a higher MDI score (p=0.056), although it was not significant, and a significantly higher PDI score (p<0.05) compared to the control formula group. At 118 weeks, the fish-DHA formula group had significantly higher MDI and PDI scores (p<0.05) compared to the control formula group. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Jensen et al., 2005 |
Randomized Controlled Trial |
Pregnant women (n=227) Aged 18-40 years Houston, TX White (75% DHA group; 79% control group) African American (19% DHA group; 13% control group) Women plan to breastfeed exclusively for ≥4 months Infant gestational age >37 weeks Infant birth weight 2500-4200 g No chronic maternal disorders; major congenital anomalies and obvious gastrointestinal or metabolic disorders of the infant |
DHA supplement |
Within 5 days after delivery until 4 months postpartum |
|
Fewtrell et al., 2004 |
Randomized Controlled Trial |
Infants (n=238) Preterm Glasgow, UK Birth weight ≤2000 g Mean maternal age about 29 years Social class 1 or 2 (18% in controls; 27% in LCPUFA group) Mothers with degree or higher (2% in controls; 7% in LCPUFA group) |
LCPUFA-supplemented formula |
Preterm formulas: when pediatrician decided that preterm formula should be started, to discharge Discharge formulas: from discharge until 9 months after term |
|
Amount |
Results |
Conclusion* |
|
High-DHA capsule (algal triacylglycerol): 0.8% LA and 41.7% DHA by weight 200 mg DHA/day Control capsule (soy and corn oil): 56.3% LA, 3.9% ALA by weight |
There were no significant differences in visual acuity from the Teller Acuity Card at 4 or 8 months of age or from the Sweep VEP at 4 months of age between the two groups. There were no significant differences in mean transient VEP latency at 4 and 8 months of age between the two groups; but the transient VEP amplitude was significantly lower in the infants of the high-DHA capsule group compared to the infants of the control capsule group (p<0.03). There were no significant differences in Gesell Gross Motor, CAT, or CLAMS DQ scores at 12 and 30 months of age or in Bayley MDI at 30 months of age between the two groups; but Bayley PDI at 30 months of age was 8.4 points higher in infants of the high-DHA capsule group compared to infants of the control capsule group. |
N |
|
LCPUFA-supplemented formulas (g/100 g fat): 12.30 LA, 0.04 AA, 1.50 ALA, 0.10 EPA, 0.50 DHA Control formulas (g/100 g fat): 11.5 LA, 1.6 ALA, no AA, EPA, or DHA |
At 18 months of age, the Bayley MDI and PDI scores did not differ significantly between the groups. At 9 months of age, overall development scores and individual subscale scores did not differ significantly between the groups. |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Bouwstra et al., 2003 |
Randomized Controlled Trial |
Infants (n=397) Term, healthy Groningen, Netherlands University and Martini Hospitals in Groningen and at midwife clinics No congenital disorders that interfered with adequate functioning in daily life; infants from multiple births; infants whose mothers did not have mastery of the Dutch language or suffered from significant illness or disability; adopted or foster infants; or formula-fed infants who had received human milk >5 days |
LCPUFA-supplemented formula |
Birth to 2 months of age |
|
Amount |
Results |
Conclusion* |
|
Control formula (in mol%): 11.56 LA, 1.27 ALA Supplemented formula (in mol%): 11.00 LA, 0.18 GLA, 0.03 DGLA, 0.39 AA, 1.30 ALA, 0.06 EPA, 0.23 DHA Breast-fed (in mol%, mean±SE): 13.62±4.24 LA, 0.11±0.03 GLA, 0.34±0.06 DGLA, 0.34±0.06 AA, 1.11±0.35 ALA, 0.06±0.04 EPA, 0.19±0.11 DHA |
After controlling for profession of mother’s partner requiring a university or vocational-college education, Obstetrical Optimality Score, and age at assessment: The control formula group had a significantly lower OR of occurrence of normal-optimal general movements at age 3 months when compared to the breastfed infants (OR=0.55; p=0.038); and Those in the supplemented formula group had a significantly lower OR of occurrence of normal-optimal general movements at age 3 months when compared to the breast-fed infants (OR=0.42; p=0.006), but the OR was not significant when compared to the control formula group (OR=0.77; p=0.41). After controlling for marital status, family history of diabetes, gestational age at birth, condition of perineum, and age at assessment: The control formula group had a significantly higher OR of mildly abnormal general movements at age 3 months when compared to the breast-fed infants (OR=2.03; p=0.039); and The supplemented formula group had a significantly lower OR of mildly abnormal general movements at age 3 months when compared to the control formula group (OR=0.49; p=0.032), but the OR was not significant when compared to the breast-fed infants (OR=0.94; p=0.87). |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Helland et al., 2003 |
Randomized Controlled Trial |
Pregnant women (n=48 in cod-liver oil group; n=36 in corn oil group) Aged 19-35 years Oslo, Norway Healthy women with, singleton pregnancy, nulli- or primiparous, intention to breast-feed No supplement of n-3 LCPUFA earlier during pregnancy, premature births, birth asphyxia, general infections, or anomalies in the infants that required special attention |
Cod-liver oil supplement |
From 18 weeks of pregnancy until 3 months after delivery |
|
Fewtrell et al., 2002 |
Randomized Controlled Trial |
Infants (n=195 formula-fed; n=88 breast-fed) Preterm Birth weight <1750 g Nottingham and Leicester, UK No congenital malformation known to affect neurodevelopment Mothers decided not to breast-feed by 10 days of age; tolerated enteral feeds at that time (for randomized groups) Social class 1 or 2 (19% in controls; 26% in LCPUFA group; 33% in breast-fed group) |
LCPUFA-supplemented formula |
10 days of age until discharge |
|
Amount |
Results |
Conclusion* |
|
Cod-liver oil: 10 mL/day 1183 mg DHA, 803 mg EPA Corn oil: 10 mL/day 4747 mg LA, 92 mg ALA |
K-ABC scores were significantly higher for the subset MPCOMP among children from the cod-liver oil group compared to the corn oil group (p=0.049). The scores for the other subtests (SEQPROC, SIMPROC, NONVERB) were also higher in the cod-liver oil group compared to the corn oil group, but they were not significant. |
B |
|
LCPUFA-supplemented formula (g/100 g fat): 12.00 LA, 0.31 AA, 0.60 ALA, 0.04 EPA, 0.17 DHA Control formula (g/100 g fat): 10.6 LA, 0.7 ALA, no detected AA, EPA, DHA |
There were no significant differences in KPS quotients at 9 months of age and neurological status at 9 or 18 months of age between the two formula groups. There were no significant differences found in Bayley MDI or PDI at 18 months of age between the two formula groups. Breast-fed infants had significantly higher KPS quotients (overall, adaptive, gross motor, fine motor, and personal-social) at 9 months of age (p<0.005) and significantly higher Bayley MDI and PDI at 18 months of age (p<0.005) compared to the control formula-fed infants. Breast-fed infants had significantly higher KPS quotients (overall, adaptive, gross motor, fine motor, and personal-social) at 9 months of age (p<0.005; p<0.05 for gross motor quotient) and significantly higher Bayley MDI and PDI at 18 months of age (p<0.005) compared to the LCPUFA-supplemented formula infants. |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Van Wezel-Meijler et al., 2002 |
Randomized Controlled Trial |
Infants (n=42) Preterm, admitted to neonatal intensive-or high-care unit of hospital Birth weight <1750 g Leiden, Netherlands Mothers not breast-feeding Normal neurological examination throughout the neonatal period Repeated ultrasound of the brain being normal or showing, at most, minor abnormalities No abnormalities of the central nervous system; abnormal neurological examination or occurrence of seizures; any systemic disease with potential negative influence on future growth or development; serious nutritional or gastrointestinal problems preventing initiation of enteral feeding after the first week postpartum or complete enteral feeding after the third week postpartum; retinopathy of prematurity grade 3 or more |
AA/DHA-supplemented formula |
2-3 weeks after birth until weighing 3000 g |
|
Amount |
Results |
Conclusion* |
|
Supplemented preterm formula: 4.4 g fat/100 mL 0.015 g/100 mL of added DHA (microalgae) 0.031 g/100 mL of added AA (fungi) Control formula: 4.4 g fat/100 mL No addition of DHA and AA |
There were no significant differences found in Bayley MDI and PDI at 3, 6, 12, or 24 months between the two groups. There were no significant differences found in myelination at 3 and 12 months between the two groups. |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Auestad et al., 2001 |
Randomized Controlled Trial |
Infants (n=294 formulafed; n=165 breast-fed) Kansas City, MO; Little Rock, AR; Pittsburgh, PA; Tucson, AZ Good health, term status, either ≤9 days of age (formula group) or ≤11 days of age and currently breast-feeding (breast-feeding group), birth weight ≥2500 g, 5-minute APGAR score ≥7, ability to tolerate milk-based formula or breast milk, guardian or parent agreement to feed the assigned study formula ad libitum according to the study design No evidence of significant cardiac, respiratory, ophthalmologic, gastrointestinal, hematologic, or metabolic disease; milk-protein allergy; or a maternal medical history known to have proven adverse effects on the fetus, tuberculosis, HIV, perinatal infections, or substance abuse 61-74% European American 60-80% mothers married Mean mothers’ age about 29 years Mean mothers’ education about 14 years |
Fish oil/fungal oil and egg-derived triglyceridesupplemented formulas |
9-11 days after birth until 12 months of age |
|
Amount |
Results |
Conclusion* |
|
Fish oil and fungal oil-supplemented preterm formula: 0.46 g AA/100 g total fatty acids ≤0.04 g EPA/100 g total fatty acids 0.13 g DHA/100 g total fatty acids Egg-derived triglyceride-supplemented preterm formula: 0.45 g AA/100 g total fatty acids No detected EPA 0.14 g DHA/100 g total fatty acids Control formula: No detected AA, EPA, DHA |
The vocabulary expression score at 14 months was significantly higher in the fish/fungal group than in the egg-TG group (p<0.05). Smiling and laughter was significantly higher in the control group than in the egg-TG group (p=0.05). No other development, cognition, vocabulary, or temperament outcomes presented were significantly different between the formula groups. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
O’Connor et al., 2001 |
Randomized Controlled Trial |
Infants (n=470) Preterm Birth weight 750-1800 g Cleveland, OH; Kansas City, MO; Little Rock, AR; Nottingham and Leeds, UK; Louisville, KY; Portland, OR; New York, NY; Santiago, Chile White (n=81 controls; n=80 fish/fungal; n=85 egg-TG) No serious congenital abnormalities that could affect growth and development; major surgery before randomization; periventricular/intra-ventricular hemorrhage greater than grade II; maternal incapacity; liquid ventilation; asphyxia resulting in severe and permanent neurologic damage; or uncontrolled systemic infection at the time of enrollment |
Fish oil/fungal oil and egg-derived triglyceride/fish oil-supplemented formulas |
In hospital formula from within 72 hours of first enteral feeding until term-corrected age Post-discharge formula from term-corrected age until 12 months of age |
|
Amount |
Results |
Conclusion* |
|
All in g/100 g total fatty acids (mean±SE) In-hospital control: 16.0±0.9 LA, 2.4±0.1 ALA, no AA, EPA, DHA In-hospital AA+DHA (fish/fungal oil): 16.80±1.00 LA, 2.60±0.30 ALA, 0.43±0.02 AA, 0.08±0.01 EPA, 0.27±0.04 DHA In-hospital AA+DHA (egg-TG/fish oil): 17.50±0.90 LA, 2.50±0.30 ALA, 0.41±0.00 AA, no EPA, 0.24±0.01 DHA Post-discharge control: 19.1±1.1 LA, 2.4±0.2 ALA, no AA, EPA, DHA Post-discharge AA+DHA (fish/fungal oil): 19.50±0.70 LA, 2.40±0.20 ALA, 0.43±0.01 AA, no EPA, 0.16±0.01 DHA Post-discharge AA+DHA (egg-TG/ fish oil): 20.30±0.40 LA, 2.40±0.20 ALA, 0.41±0.02 AA, no EPA, 0.15±0.02 DHA |
The mean novelty preference of the egg-TG/fish oil formula group was significantly greater than the control group (p=0.02) and the fish/fungal formula group (p=0.003) at 6 months corrected age. Using a Bonferroni adjusted alpha level of 0.0083, the difference between the fish/fungal formula group and the egg-TG/fish formula group was statistically significant. “Vocabulary comprehension did not differ among the 3 study formula groups at either 9 or 14 months corrected age in either the intent-to-treat or subgroup analysis.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Birch et al., 2000 |
Randomized Controlled Trial |
Infants (n=56) Healthy, term, birth weight appropriate for gestational age Singleton births Dallas, TX Predominantly White About 65% mothers had a college or postgraduate education No family history of milk protein allergy; genetic or familial eye disease; vegetarian or vegan maternal dietary patterns; maternal metabolic disease, anemia; or infection; presence of a congenital malformation or infection; jaundice; perinatal asphyxia; meconium aspiration; or any perinatal event that resulted in placement in the neonatal intensive care unit |
AA-enriched formula |
0-4 days of age to 17 weeks of age |
|
Lucas et al., 1999 |
Randomized Controlled Trial |
Infants (n=309 formula-fed; n=138 breast-fed) Healthy, term, singleton pregnancies, appropriate size for gestational age Nottingham and Leicester, UK Mean maternal age about 27 years 93.5% married About 70% with no higher school qualifications |
LCPUFA-supplemented formula |
Birth until 6 months of age |
|
Amount |
Results |
Conclusion* |
|
Enfamil + iron Enfamil + iron + 0.35% DHA Enfamil + iron + 0.36% DHA + 0.72% AA |
The mean Bayley MDI score at 18 months was significantly higher in the DHA/AA-supplemented formula group than in the control formula group (p<0.05). The mean Bayley PDI score at 18 months was not statistically different among the three groups (p=0.13). The mean Behavioral Rating Scale score at 18 months was not statistically different among the three groups (p=0.30). |
B |
|
LCPUFA-supplemented formula: 15.90% LA, 0.30% AA, 1.40% ALA, 0.01% EPA, 0.32% DHA Control formula: 12.4% LA, 1.1% ALA |
There were no significant differences in Bayley MDI and PDI at 18 months or in Knobloch, Passamanick, and Sherrard’s test at 9 months between the two formula groups. There were no significant differences in stools to 6 months, crying time (minutes/day) to 6 months, or formula intake to 6 months between the two formula groups. There were no significant differences in the OR of infection-related outcomes or the prescription of antibiotics at 9 months between the two formula groups. |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Scott et al., 1998 |
Randomized Controlled Trial |
Infants (n=274) Healthy, full-term Kansas, MO; Portland, OR; Seattle, WA No prematurity, intrauterine growth retardation, congenital anomalies, 5-minute APGAR score <7, or other significant perinatal medical complications |
AA/DHA-supplemented formula |
Those randomized, formula from first week after delivery Those exclusively breastfeeding, breast milk for first 3 months and then supplementation with Similac + iron Solid food supplementation at 4 months |
|
Willatts et al., 1998a |
Randomized Controlled Trial |
Infants (n=44) Term UK Mothers from a single maternity hospital |
LCPUFA-supplemented formula |
Birth to 4 months of age |
|
Amount |
Results |
Conclusion* |
|
Control formula: No added LCPUFA DHA formula group (fish oil): 0.2wt% DHA DHA+AA formula group (egg yolk phospholipid): 0.12wt% DHA, 0.43wt% AA |
There were no significant differences in Bayley scores among the groups for either the Mental Index or the Motor Index. After controlling for maternal education and site, when comparing all four groups, the vocabulary comprehension score at 14 months was significantly lower in the DHA formula group compared to the breast-feeding group (p=0.017). After controlling for maternal education and site, when comparing only the three formula groups, the vocabulary production score at 14 months was significantly lower in the DHA formula group compared to the control formula group (p=0.027). No other reported associations between MacArthur Communicative Development Inventories at 14 months and the formula groups and those breast-feeding were found to be significant. |
A |
|
Unsupplemented formula (g/100 g fat): 11.40 LA, 0.70 ALA, <0.10 AA, no DHA LCPUFA-supplemented formula (g/100 g fat): 11.50-12.80 LA, 0.60-0.65 ALA, 0.30-0.40 AA, 0.15-0.25 DHA |
The median quartiles for entire problem intention score (p=0.035) and the cover step intention score (p=0.032) were significantly higher in the LCPUFA-supplemented group compared to the unsupplemented group. The median quartiles for entire problem intentional solutions score (p=0.021) and cover step intentional solutions (p=0.005) were significantly higher in the LCPUFA-supplemented group compared to the unsupplemented group. There were no significant differences in the median quartiles for the barrier step or cloth step for either the intention score or the intentional solutions score. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Willatts et al., 1998b |
Randomized Controlled Trial |
Infants (n=40) Term Birth weight 2500-4000 g Dundee, UK Mean maternal age about 27 years Mean maternal education about 17 years Demonstrated either an early or late peak fixation on the habituation assessment undertaken at 3 months of age |
LCPUFA-supplemented formula |
Birth to 4 months of age |
|
Carlson and Werkman, 1996 |
Randomized Controlled Trial |
Infants (n=59) Mean gestational age about 28 weeks Birth weight 747-1275 g Predominantly Black Memphis, TN Mean mothers’ education about 12 years No need for mechanical ventilation at that time; intraventricular hemorrhage > grade 2; retinopathy of prematurity > stage 2; surgery for necrotizing enterocolitis; weight < the fifth percentile for gestational age; history of maternal substance abuse |
DHA-supplemented formula |
Preterm formula from 3 days to 2 months of age Term formula from 2 months to 12 months of age |
|
Amount |
Results |
Conclusion* |
|
Unsupplemented formula (g/100 g fat): 11.40 LA, 0.70 ALA, <0.10 AA, no DHA LCPUFA-supplemented formula (g/100 g fat): 11.50-12.80 LA, 0.60-0.65 ALA, 0.30-0.40 AA, 0.15-0.25 DHA |
There were no significant differences in 9-month problem-solving scores (intention score and number of solutions) between the two groups. For those who had an early peak fixation at 3 months, there were no significant differences in 9-month problem-solving score (intention score or intentional solutions) between the two groups (p=0.18). For those who had a late peak fixation at 3 months, the number of intentional solutions was significantly higher in the LCPUFA-supplemented group compared to the unsupplemented group (p<0.02). |
B |
|
All in g/100 g total fatty acids Preterm control formula: 21.20 LA, 2.40 ALA, no EPA or DHA Preterm DHAsupplemented formula: 21.20 LA, 2.40 ALA, 0.06 EPA, 0.20 DHA Term formula: 34.30 LA, 4.80 ALA, no EPA or DHA |
At 12 months of age, the DHA-supplemented group had statistically more number of looks to familiar (p<0.05) and less seconds of time/novel looks (p<0.05) compared to the controls. No other statistically significant results were reported on visual attention. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Werkman and Carlson, 1996 |
Randomized Controlled Trial |
Infants (n=67) Mean gestational age 29 weeks Birth weight 748-1398 g Can tolerate enteral; intakes >462 kJ/kg body weight/day for 5-7 days Predominantly Black Memphis, TN Mean maternal age 23 years Mean mothers’ education about 11.5 years No need for mechanical ventilation at that time; intraventricular hemorrhage > grade 2; retinopathy of prematurity > stage 2; surgery for necrotizing enterocolitis; weight < the fifth percentile for gestational age; history of maternal substance abuse |
DHA-supplemented formula |
Preterm formula until discharge Term formula from discharge until 9 months past term Other foods gradually added to diet at about 4 months past term Mixed diet, including whole cow’s milk from 9 to 12 months |
|
Agostoni et al., 1995 |
Randomized Controlled Trial |
Infants (n=86) Mothers’ mean age = about 30 years Gestational age between 37-42 weeks, weight at birth appropriate for gestational age Milan, Italy APGAR score better than 7 at 5 minutes, absence of disease |
LCPUFA-supplemented formula |
Within 3 days until 4 months of age |
|
Amount |
Results |
Conclusion* |
|
All in g/100 g total fatty acids Preterm control formula: 19.1 LA, 3.0 ALA, no EPA or DHA Preterm DHA-supplemented formula: 18.7 LA, 3.1 ALA, 0.3 EPA, 0.2 DHA Term control formula: 33.2 LA, 4.8 ALA, no EPA or DHA Term DHA-supplemented formula: 32.6 LA, 4.9 ALA, 0.3 EPA, 0.2 DHA |
“Diet did not significantly influence look duration during familiarization, but there was a trend toward shorter look duration in DHA-supplemented infants compared to the controls.” At 6.5 months of age, the DHA-supplemented group had a statistically higher number of total looks (p<0.01), number of looks to novel (p<0.01), and number of looks to familiar (p<0.05) compared to the controls. At 9 months of age, the DHA-supplemented group had a statistically higher number of total looks (p<0.01), number of looks to novel (p<0.01), number of looks to familiar (p<0.05), and less seconds for average time/look (p<0.05) compared to the controls. At 12 months, the DHA-supplemented group had a statistically shorter novel time as a percentage of total time (p<0.05), more seconds of time to familiar (p<0.05), and a higher number of total looks (p<0.01), number of looks to novel (p<0.05), and number of looks to familiar (p<0.05) compared to the controls. No other significant results were reported for visual attention. |
B |
|
Supplemented formula (g/100 g fat): 10.80 LA, 0.30 GLA, 0.73 ALA, 0.44 AA, 0.05 EPA, 0.30 DHA Standard formula (g/100 g fat): 11.10 LA, 0.70 ALA Human milk (g/100 g fat): 6.9-16.4 LA, 0.1-0.9 GLA, 0.7-1.3 ALA, 0.2-1.2 AA, 0.0-0.6 EPA, 0.1-0.6 DHA |
The mean developmental quotient (DQ) at 4 months for those in the standard formula group was statistically lower from the DQ in the supplemented formula group (p<0.05) and the breast-feeding group (p<0.05). There was no statistical difference between the mean DQ at 4 months of the supplemented formula group and the breast-feeding group. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
McCann and Ames, 2005 |
Review |
Summary of observational, RCTs, other experimental and animal studies |
DHA status and LCPUFA-supplemented formula |
|
|
Bryan et al., 2004 |
Review |
Summary of the literature (all designs) |
PUFA from breast milk or formula |
|
|
Jacobson, 1999 |
Review |
Mostly 2 prospective longitudinal studies Detroit study on effects of prenatal exposure to alcohol Michigan study of effects of pre- and postnatal exposure to PCBs |
LCPUFA-supplemented formula |
|
|
Amount |
Results |
Conclusion* |
|
|
“Evidence from chronic dietary restriction rodent studies … shows that the addition of DHA to diets of animals whose brain concentration of DHA have been severely reduced restored control performance levels.” “Formula comparison and maternal supplementation studies in humans and ALA dietary restriction studies in nonhuman primates both link the availability of n-3 LCPUFAs to the development of visual attention” and higher DHA status to enhanced neuromotor development. RCTs in humans have often shown no effect of “LCPUFA supplementation on cognitive or behavioral performance and some reviewers have considered that, overall, the evidence was insufficient to conclude that LCPUFA supplementation benefited development.” |
B |
|
|
“There is moderate evidence that PUFAs, and long-chain omega-3 PUFAs in particular, from either breast milk or supplemented infant formula, are beneficial in the development of visual acuity and cognitive performance in infants.” “There is very limited empirical evidence, due to the small number of extant studies, for the beneficial effects of PUFAs, and omega-3 PUFAs in particular, on cognitive performance in older children.” “Evidence suggest that omega-3 PUFAs may have a role in the control of the symptoms of neurological disorders such as ADHD and dyslexia.” |
B |
|
|
“Any comparisons between breastfed and supplemented groups should include measures of maternal IQ and quality of parenting on which these groups tend to differ.” “Animal and human studies indicating a relation between LCPUFA supplementation and enhanced visual acuity and shorter visual fixations may, in fact, represent relatively independent effects of supplementation on both acuity and cognitive processing speed.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Daniels et al., 2004 |
Cohort |
Infants (n=1054) Mothers’ mean age = 29 years Majority of mothers with at least an O level (moderate) education Bristol, UK Singleton, term births Avon Longitudinal Study of Parents and Children (ALSPAC) |
Seafood |
Maternal fish intake: 32 weeks of gestation Breast-feeding practices: 15 months after birth Infant fish intake: 6 and 12 months after birth Total mercury concentration: Cord blood at birth |
|
Innis et al., 2001 |
Cohort |
Infants (n=83) Term Birth weight 2500-4500 g Mean mothers’ age 32 years British Columbia Intend to breast-feed for 3 months, no solid foods for at least the first 4 months after birth No mothers with substance abuse, communicable diseases, metabolic or physiologic problems, infections likely to influence fetal growth, or multiple births No infants with evidence of metabolic or physical abnormalities |
Fatty acids in blood from infants and milk from mothers |
2 months of age |
|
Amount |
Results |
Conclusion* |
|
Maternal fish intake categories (during pregnancy): 1 = Rarely/never 2 = 1 meal/2 weeks 3 = 1-3 meals/week 4 = 4+ meals/week Child fish intake categories (6 months of age): 1 = Rarely/never 2 = 1+ meal/week Child fish intake categories (12 months of age): 1 = Rarely/never 2 = 1+ meal/week |
Children whose mothers ate 1-3 fish meals/week and 4+ fish meals/week had significantly lower odds of low MCDI scores for social activity (OR=0.6, 95% CI 0.5-0.8 and OR=0.7, 95% CI 0.5-0.9, respectively) than the children whose mothers rarely or never ate fish during pregnancy. Children whose mothers ate 1-3 fish meals/week and 4+ fish meals/week had significantly lower odds of low DDST scores for language (OR=0.7, 95% CI 0.5-0.9 and OR=0.7, 95% CI 0.5-0.9, respectively) than the children whose mothers rarely or never ate fish during pregnancy. Children who ate 1+ fish meals/week had significantly lower odds of low MCDI scores for vocabulary comprehension (OR=0.7, 95% CI 0.5-0.8) and social activity (OR=0.7, 95% CI 0.6-0.9) and total DDST score (OR=0.8, 95% CI 0.6-0.9). All other odds ratios presented were nonsignificant. |
B |
|
Infant DHA: (g/100 g fatty acids) Plasma phospholipids = 2.2-8.0 RBC PE = 6.3-13.0 PC = 1.4-4.6 Infant AA: (g/100 g fatty acids) Plasma phospholipids = 8.1-15.8 RBC PE = 20.2-27.8 PC = 5.6-9.7 Mother’s milk: (g/100 g milk fatty acids) DHA = 0.10-2.50 AA = 0.20-0.81 LA = 6.30-21.50 LNA = 0.50-4.10 |
“The ability to correctly discriminate a retroflex compared with dental phonetic contrast at 9 months of age was positively correlated with the plasma phospholipid DHA (p<0.02) and the RBC PE at 2 months of age (p=0.02).” “There were no significant correlations between the infants’ AA status and the ability to discriminate the native or nonnative language contrasts.” “There were no significant correlations between the infant DHA or AA status at 2 months of age and test scores for novelty preference, or the job search task, with adjustments for covariates included in the model.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Kodas et al., 2004 |
Animal |
2 generations of female Wistar rats |
ALA-deficient diet |
Control group: Control diet at birth to 60 days after birth Deficient group: Deficient diet at birth to 60 days after birth Diet reversed group 1: Control diet at day of birth until 60 days after birth Diet reversed group 2: Deficient diet until day 7 postpartum and then control diet from day 7 to day 60 postpartum Diet reversed group 3: Deficient diet until day 14 postpartum and then control diet from day 14 to day 60 postpartum Diet reversed group 4: Deficient diet until day 21 postpartum and then control diet from day 21 to day 60 postpartum |
|
Amount |
Results |
Conclusion* |
|
ALA-deficient diet: 6% fat African peanut oil <6 mg ALA/100 g of diet 1200 mg LA/100 g of diet Control diet: 60% peanut oil, 40% rapeseed oil 200 mg ALA/100 g of diet 1200 mg LA/100 g of diet |
The fatty acid composition of phosphatidylcholine in the hippocampus of 2-month-old rats was as follows: AA was not significantly different among the different diet groups; DHA was significantly higher in the control group and all diet reversed groups compared to the deficient group (p<0.05); n-6:n-3 was significantly lower in the control group and all diet reversed groups compared to the deficient group (p<0.05). These differences were not significant between the control group and the diet reversed groups. The fatty acid composition of phosphatidylethanolamine in the hippocampus of 2-month-old rats was as follows: AA was significantly lower in the control group and all diet reversed groups compared to the deficient group (p<0.05); DHA was significantly higher in the control group and all diet reversed groups compared to the deficient group (p<0.05); n-6:n-3 was significantly lower in the control group and all diet reversed groups compared to the deficient group (p<0.05). These differences were not significant between the control group and the diet reversed groups. The fatty acid composition of phosphatidylserine in the hippocampus of 2-month-old rats was as follows: AA was not significantly different among the different diet groups; DHA was significantly higher in the control group and all diet reversed groups compared to the deficient group (p<0.05); n-6:n-3 was significantly lower in the control group and all diet reversed groups compared to the deficient group (p<0.05). These differences were not significant between the control group and the diet reversed groups. Basal 5-HT levels were significantly higher in the deficient group compared with the control group (p<0.05); there were no significant differences in basal 5-HT levels between the diet reversed groups 1, 2, and 3 and the control group; there were no significant differences in basal 5-HT levels between the diet reversed group 4 and the control group, deficient group, and all other diet reversed groups. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Levant et al., 2004 |
Animal |
Adult female Long-Evans rats |
AA/EPA/DPA/DHA-deficient diet |
Control diet: Day 1 of pregnancy until end of study Deficient diet: Day 1 of pregnancy until postnatal day 21. Postnatal day 21, half on deficient diet were changed to remediation diet and half stayed on deficient diet |
|
Chalon et al., 2001 |
Animal |
Male rats 2-3 months old |
ALA-deficient diet |
2-3 months of age |
|
Amount |
Results |
Conclusion* |
|
Control diet: 0.35 kg/5 kg diet from soybean oil; no detected AA, EPA, DPA, or DHA Deficient diet: 0.35 kg/5 kg diet from sunflower oil; no detected AA, EPA, DPA, or DHA Remediation diet: 0.3275 kg/5 kg diet from sunflower oil and 0.0225 kg/5 kg diet from fish oil AA = 0.1 g/100 g fatty acids EPA = 1.6 g/100 g fatty acids DPA = 0.4 g/100 g fatty acids DHA = 3.5 g/100 g fatty acids |
“Rats raised on the deficient diet exhibited a decrease in brain DHA content to 80% of control animals at maturity (p<0.05)” and an “increase in DPA content to 575% of control animals at maturity (p<0.001).” The remediation diet restored brain DHA and DPA content to levels similar to those on the control diet. Catalepsy score was significantly lower in the deficient diet group compared to the control group (p<0.05) and the remediation diet group (p<0.05). In a test of locomotor activity in a novel environment, the deficient diet group exhibited 187% of the activity of the control diet group during the 2-hour observation (p<0.05); results were similar between the deficient diet group and the remediation diet group. In the test of amphetamine-stimulated locomotor activity, the deficient diet group exhibited 144% of the activity of the control group (p<0.05). |
A |
|
ALA-deficient diet: 1200 mg LA/100 g diet, <6 mg ALA/100 g diet African peanut oil Diet balanced in n-6 and n-3 PUFA: 1200 mg LA/100 g diet, 200 mg ALA/100 g African peanut oil and rapeseed oil |
“Intake of PUFA constitutes an environmental factor able to act on the central nervous system function.” “Chronic dietary deficiency in ALA in rats induces abnormalities in several parameters of the mesocortical and mesolimbic dopaminergic systems.” “It is proposed that strong links exist among PUFA status, neurotransmission processes, and behavioral disorders in humans.” |
B |
|
Amount |
Results |
Conclusion* |
|
4 formula diets (all in g/100 g): Diet 1 (Diet D-): 1.6 LA, 0.1 ALA, no GLA, AA, or DHA Diet 2 (Diet D+): 1.9 LA, 0.1 GLA, 0.4 AA, 0.1 ALA, 0.3 DHA Diet 3 (Diet C-): 15.6 LA, 1.5 ALA, no GLA, AA, or DHA Diet 4 (Diet C+): 16.4 LA, 0.1 GLA, 0.4 AA, 1.6 ALA, 0.3 DHA |
There were no significant differences in brain weight, brain protein, DNA, cholesterol or phospholipid concentrations, or CNPase activity among the different diet groups. Piglets fed formulas with AA and DHA had significantly higher frontal cortex dopamine, HVA, norepinephrine, tryptophan and serotonin concentrations than piglets fed formulas without AA and DHA. The concentrations of all frontal cortex monoamines and metabolites in piglets fed Diet 2 formula were not different from those of piglets fed Diets 3 and 4. The inclusion of AA and DHA in Diet 4 had no significant effect on any of the frontal cortex monoamines or metabolites measured, compared to Diet 3. |
B |
|
ALA-deficient diet: 6% fat as peanut oil 6 mg ALA/100 g diet 1200 mg LA/100 g diet Control diet: 60% peanut oil, 40% rapeseed oil 200 mg ALA/100 g diet 1200 mg LA/100 g diet |
In the control diet group, n-3 (mostly DHA) levels reached a maximum in the stratium and a minimum in the frontal cortex at 12 months of age and remained unchanged during aging in the cerebellum. “In the deficient diet group, DHA content considerably reduced as compared with controls.” No specific effects of the deficient diet were found on the proportion of any phospholipid classes. In the control diet group, dopamine levels reached a maximum at 6 months of age, were decreased up to 12 months of age, and then stabilized in the stratium and frontal cortex. However, “the levels were not diet related in the stratium but were dramatically reduced in the frontal cortex of deficient rats and remained unchanged throughout all ages.” In the control diet group, 5-HT levels increased between 2 and 6 months of age in the stratium and then stabilized; they did not change in the frontal cortex or cerebellum during aging. |
N |
TABLE B-1h Studies on Allergies: Effects on Infants Supplemented with Omega-3 Fatty Acids in Formula
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Calder, 2001 |
Review |
Summary of animal studies and human trials |
Fish-oil supplement |
|
|
Field et al., 2001 |
Review |
Summary of animal studies and human trials |
AA/DHA-supplemented formula |
|
|
Amount |
Results |
Conclusion* |
|
|
“Animal studies have shown that dietary fish oil results in altered lymphocyte function and in suppressed production of proinflammatory cytokines by macrophages.” “Clinical studies have reported that fish-oil supplementation has beneficial effects in rheumatoid arthritis, inflammatory bowel disease, and among some asthmatics.” “The effect of fatty acids during pregnancy upon the maternal immune system and upon that of the infant are not known.” |
B |
|
|
“Recent research has been directed at the neurological, retinal, and membrane benefits of adding AA and DHA to infant formula. In adults and animals, feeding DHA affects T-cell function. However, the effect of these lipids on the development and function of the infant’s immune system is not known.” “The addition of small amounts of DHA and AA (at levels similar to that in human milk) to preterm infant formula can influence the concentration, proportion, maturation, and cytokine production of peripheral blood lymphocytes.” |
N |
|
Amount |
Results |
Conclusion* |
|
Standard commercial preterm formula group (% weight of total fatty acids): 12.8 LA, 1.4 ALA, no AA or DHA Supplemented preterm formula group (% weight of total fatty acids): 12.10 LA, 1.50 ALA, 0.49 AA, 0.35 DHA |
At 14 days postpartum, infants in the supplemented formula group had significantly higher hematocrit (L/L) concentrations compared to those in the human milk group (p<0.05). At 14 days postpartum, infants in the human milk group had significantly higher monocytes compared to both the standard formula group and the supplemented formula group (p<0.05). At 42 days postpartum, infants in the standard formula group had significantly higher T helper phenotypes and CD4/CD8 phenotypes compared to both the supplemented formula group and the human milk group (p<0.05). At 42 days postpartum, infants in the standard formula group had significantly lower monocytes compared to the human milk group (p<0.05). At 42 days postpartum, infants in the human milk group had significantly higher B cells compared to those in both formula groups (p<0.05). At 42 days postpartum, infants in the standard formula group had significantly higher sIL-2R production compared to the supplemented formula group (p<0.05) and significantly lower IL-10 production compared to the human milk group (p<0.05). No other reported results were found to be significant. |
B |
TABLE B-1i Studies on ADHD: Effects on Children Supplemented with Omega-3 Fatty Acids in Foods Other Than Exclusively Breast Milk or Infant Formula Experimental Studies in Humans
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Richardson, 2004 |
Review |
Summary of RCTs |
HUFA supplement |
|
|
Hirayama et al., 2004* |
Randomized Controlled Trial |
Children (n=40) Aged 6-12 years Recruited from a summer camp for children with psychiatric disorders Diagnosed or suspected as ADHD |
DHA supplement |
2 months |
|
Amount |
Results |
Conclusion** |
|
|
Omega-3 fatty acids, particularly EPA, may be beneficial in the management of dyslexia, dyspraxia, and ADHD. There is no evidence that omega-6 fatty acids are beneficial in the management of dyslexia, dyspraxia, and ADHD, but positive results have been found using an omega-3:omega-6 combination for both ADHD and dyslexia. |
B |
|
DHA group: Fermented soybean milk 3 times/week (600 mg DHA/125 mL) Bread rolls 2 times/week (300 mg DHA/45 g) Steamed bread 2 times/week (600 mg DHA/60 g) Total = 3600 mg DHA, 700 mg EPA/week Control group: Placebo food containing olive oil instead of DHA-rich fish oil |
Short-term visual memory was significantly improved in the control group from baseline until the end of the study (p=0.02), but not in the DHA group. The short-term visual memory was significantly better in the control group than in the DHA group (p=0.02). The number of errors of omission and commission were significantly improved in the continuous performance test in the control group from baseline until the end of the study (p=0.02 and p=0.01, respectively). The number of errors of commission were significantly higher in the DHA group than in the control group (p=0.001). |
A |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Harding et al., 2003* |
Trial |
Boys and girls (n=20) Aged 7-12 years Diagnosed with ADHD No other medication or treatment, street drugs, other nutritional or botanical supplements, comorbid disorders |
Multivitamin, multiple mineral, phytonutrients, essential fatty acid supplements |
4 weeks |
|
Stevens et al., 2003* |
Randomized Controlled Trial |
Boys and girls (n=47) Aged 6-13 Central Indiana = 100-mile radius of West Lafayette Those with diagnosed ADHD and those without ADHD No chronic health problems Presence of 1+ severe symptoms or several mild symptoms |
PUFA supplement |
4 months |
|
Amount |
Results |
Conclusion** |
|
Groups determined by parental choice Ritalin group: 5-15 mg Ritalin 2-3 times daily Supplement group: A multivitamin, multi-mineral, phytonutrients, essential fatty acids (180 mg EPA and 120 mg DHA from salmon oil and 45 mg GLA from borage oil) and phospholipids (soy lecithin), probiotics, and amino acids |
Both the Ritalin group and the supplement group showed significant gains in the Full Scale Response Control Quotient and the Full Scale Attention Control Quotient scores (p≤0.01 and p≤0.001, respectively). There were no significant differences in improvement between the two groups. |
B |
|
PUFA group: 8 capsules of PUFA/day 60 mg DHA, 10 mg EPA, 5 mg AA, 12 mg GLA, 3 mg vitamin E/capsule Placebo group: 8 capsules of placebo/day 0.8 g olive oil/capsule |
Based on those who completed the intervention, the change in teacher hit reaction time (measured both in ms and T-score) was significantly greater in the PUFA group than in the placebo group (p=0.05 and p=0.02, respectively) at 4 months. At baseline, there were no significant differences in parents’ DBD and teachers’ DBD scores between the two groups; after 4 months of treatment the number of children who improved on the parents’ DBD attention and oppositional/defiant disorder scales was significantly higher in the PUFA group than in the placebo group (p=0.09 and p=0.02, respectively). No other significant differences were found between the two groups. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Richardson and Puri, 2002* |
Randomized Controlled Trial |
Boys and girls (n=41) Aged 8-12 years Northern Ireland Referred to a school for children with specific literacy problems No official diagnosis of ADHD or any other psychiatric disorder; use of fatty acid supplements in last 6 months; consumption of oily fish >2 times/week; history of any other neurological or major psychiatric disorder or other significant medical problems; not in treatment for ADHD |
HUFA supplement |
12 weeks |
|
Amount |
Results |
Conclusion** |
|
Supplement group: 186 mg EPA/day, 480 mg DHA/day, 96 mg GLA/day, 60 IU vitamin E/day, 864 mg LA/day, 42 mg AA/day, 8 mg thyme oil/day Placebo: Olive oil |
At 3 months, the mean psychosomatic ADHD subscale, mean Conners’ ADHD index score, and mean DSM inattention score were significantly lower in the supplemented group than in the placebo group (p=0.05, p=0.03, p=0.05, respectively). At 12 weeks, the improvements were significantly greater for the supplemented group compared to the placebo group for the cognitive problems (p=0.01), the anxious/shy subscales (p=0.04), and the Conners’ index global scale (p=0.02). |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Brue et al., 2001 |
Randomized Controlled Trial |
Boys and girls (n=51) Aged 4-12 years Referred by parents, pediatricians, psychologists, psychiatrists, and educators ADHD diagnosed by a physician or psychologist No serious and preexisting medical or psychological condition or taking a stimulant medication other than Ritalin |
Essential fatty acid supplement |
Two 12-week trials |
|
Amount |
Results |
Conclusion** |
|
Trial 1: Treatment Group and Ritalin + Treatment Group: 10 mg Ginkgo biloba, 200 mg Melissa officinalis, 30 mg Grapine, 35 mg dimethylaminoethanol, 100 mg 1-glutamine Placebo Group and Ritalin + Placebo Group: 200 mg Slippery elm supplement Trial 2: Double Treatment Group and Ritalin + Double Treatment Group: 20 mg Ginkgo biloba, 400 mg Melissa officinalis, 60 mg Grapine, 70 mg dimethylaminoethanol, 200 mg 1-glutamine Double Treatment + EFA Group and Ritalin + Double Treatment + EFA Group: 20 mg Ginkgo biloba, 400 mg Melissa officinalis, 60 mg Grapine, 70 mg dimethylaminoethanol, 200 mg 1-glutamine, 1000 mg flaxseed |
Based on parent and teacher reports from Trial 1, there were no significant differences in inattentiveness or hyperactive-impulsive subscales between any of the treatment groups and their respective controls. Based on parent reports from Trial 2, those in the double treatment + EFA group had a significantly lower hyperactive-impulsive subscale score than the double treatment group (p=0.03). Based on teacher reports from Trial 2, those in the Ritalin + double treatment + EFA group had a significantly higher inattentive subscale score than the Ritalin + double treatment group (p=0.04). Based on teacher reports from Trial 2, those in the double treatment + EFA group had a significantly higher hyperactive-impulsive subscale score than the double treatment group (p=0.04). |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Voigt et al., 2001* |
Randomized Controlled Trial |
Boys and girls (n=63) Aged 6-12 years 100% White in DHA group; 85% White in placebo group Texas No ineffective treatment with stimulant medication; treatment with other psychotropic medications; previous diagnosis of other childhood psychiatric disorders; use of dietary supplements; occurrence of a significant life event within 6 months; history of head injury or seizures; receipt of special education services for mental retardation or a pervasive developmental disorder; premature birth; exposure to tobacco, alcohol, or other drugs in utero; diagnosis of a disorder of lipid metabolism or other chronic medical condition Previous diagnosis of ADHD Being treated successfully with stimulant medication |
Algae-derived triglyceride supplement |
4 months |
|
Amount |
Results |
Conclusion** |
|
Algae-derived TG capsule: 345 mg DHA/day |
Between baseline and 4 months, TOVA errors of omission significantly increased (p=0.03-0.01) and color trails 1 (p=0.03-0.01) and color trails 2 (p=0.001) significantly decreased for the supplemented group. Between baseline and 4 months, TOVA errors of commission (p<0.0003) and color trails 2 (p<0.0003) significantly decreased and TOVA total response time (p=0.03-0.01) significantly increased for the placebo group. “There were no differences between groups at any time on any behavior measure by the parental Conners’ Rating Scales.” |
N |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Stevens et al., 1995* |
Case-control |
Cases = boys with ADHD (n=53) Control = healthy boys (n=43) Aged 6-12 years North central Indiana Primarily White |
Plasma fatty acid analysis |
At time of visit |
|
Mitchell et al., 1987* |
Case-control |
Cases = hyperactive children (n=48) Controls = from two local primary schools (n=49) Boys and girls Mean age about 9 years 92% European About 95% mothers in top three socioeconomic groups Auckland, New Zealand |
Serum fatty acid levels |
At time of visit |
|
Mitchell et al., 1983* |
Case-control |
Cases = from a residential school for “maladjusted” children (n=23) Controls = from a normal intermediate school (n=20) Boys and girls Aged 10-13 years for controls Aged 7.5-13 years for cases Auckland, New Zealand |
Level of red blood cell essential fatty acids |
At time of visit |
|
*Included in Schachter HM, Kourad K, Merali Z, Lumb A, Tran K, Miguelez M. 2005. Effects of Omega-3 Fatty Acids on Mental Health. Summary, Evidence Report/Technology Assessment No. 116 (Prepared by the University of Ottawa Evidence-based Practice Center under Contract No. 290-02-0021). Rockville, MD: Agency for Healthcare Research and Quality. **B = Evidence of a benefit; A = Evidence of an adverse effect; N = Evidence of no association or no clear association. |
||||
|
Amount |
Results |
Conclusion** |
|
Omega-3 fatty acids as continuous variables |
Boys with ADHD had significantly lower mean levels of plasma AA, EPA, and DHA than the controls (p<0.02, p<0.02, p<0.03, respectively). Boys with ADHD had significantly lower mean levels of red blood cell AA (p<0.02), 22:4n-6 (p<0.03), and DHA (p<0.06), and significantly higher mean levels of red blood cell 22:5n-6 (p<0.05) compared to the controls. |
B |
|
Omega-3 fatty acids as continuous variables |
The mean level of DHA from nonfasting blood samples was significantly lower in the hyperactive children than in the controls (p=0.045). The mean levels of DGLA and AA from nonfasting blood samples were significantly lower in the hyperactive children than in the controls (p=0.007 and p=0.027, respectively). No significant differences in blood serum n-3 or n-6 fatty acids were found. |
B |
|
Omega-3 fatty acids as continuous variables |
The mean levels of LA, DGLA, and AA from fasting blood samples were lower in the “maladjusted” children than in the normal children (0.05<p<0.01), although the differences were not significant. The mean level of 22:5n-6 from fasting blood samples was higher in the “maladjusted” children than in the normal children (0.05<p<0.1), although this difference was not significant. No other significant differences were found between the two groups in terms of fatty acid levels in fasting blood samples. |
N |
TABLE B-1j Studies on Allergies and Asthma: Effects on Children Supplemented with Omega-3 Fatty Acids in Foods Other Than Exclusively Breast Milk or Infant Formula
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Peat et al., 2004 |
Randomized Controlled Trial |
Pregnant women (n=616) Mean age about 29 years About 47% tertiary educated Sydney, Australia At least one parent or sibling with current asthma or frequent wheeze; fluency in English; a telephone at home; residence within 30 km of the recruitment center No pet at home; vegetarian diet; multiple births; or less than 36 weeks gestation The Childhood Asthma Prevention Study (CAPS) |
Tuna-fish oil supplement |
Child’s age of 6 months to 3 years |
|
Hodge et al., 1998* |
Randomized Controlled Trial |
Boys and girls (n=39) Aged 8-12 years Sydney, Australia Asthmatic with a history of episodic wheeze in the last 12 months and airway hyperresponsiveness to histamine No other significant diseases; taking regular oral corticosteroids or with known aspirin or dietary salicylate sensitivity |
EPA/DHA supplement |
6 months |
|
Amount |
Results |
Conclusion** |
|
Intervention group: 500 mg/day tuna fish oil 184 mg omega-3 fatty acids Placebo group: Sunola oil 83% monounsaturated oil |
At 3 years of age, there were no significant differences in prevalence of asthma, wheezing, eczema, and atopy between the intervention group and the placebo group. However, those in the intervention group had significantly lower prevalence of mild or moderate coughing (p=0.03) and atopic coughing (p=0.003) than the placebo group. |
N |
|
Omega-3 group: 0.18 g EPA and 0.12 g DHA/capsule 4 capsules/day = 1.2 g omega-3/day Omega-6 group: 0.45 g safflower oil, 0.45 g palm oil, 0.10 g olive oil/capsule No EPA or DHA |
“There was no significant change in spirometric function, dose response ratio to histamine or asthma severity score at either 3 or 6 months in either group.” “There were no significant differences between groups in TNFα production over time (p=0.22).” “Dietary enrichment of omega-3 fatty acids over 6 months increased plasma levels of these fatty acids, reduced stimulated tumour necrosis factor α production, but had no effect on the clinical severity of asthma in these children.” |
N |
|
Amount |
Results |
Conclusion** |
|
|
“Very few studies investigated the effects of polyunsaturated fatty acids (PUFAs) on chronic obstructive pulmonary disease (COPD) and asthma, and the results of those that were found showed conflicting results.” “It is very difficult to draw any conclusions on the true impact of dietary PUFA intake on respiratory health.” “The evidence in this review suggests that diet does play a role in asthma and COPD, but the causality of association cannot be confirmed because of the observational nature of most of the studies.” |
N |
|
|
“The findings of several large studies in adults suggest that high fish intake has beneficial effects on lung function.” “The relationship between fish intake and respiratory symptoms and clinical disease is less evident.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Peat et al., 1998* |
Review |
Longitudinal cohort studies and cross-sectional studies |
Diet |
|
|
Amount |
Results |
Conclusion** |
|
|
In cross-sectional studies, the risk factors for presence in:
In longitudinal studies, the risk factors for ongoing conditions from:
Important future longitudinal studies will be those that divide the broad spectrum of asthma into phenotypic groups. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Takemura et al., 2002* |
Case-control |
Cases = currently asthmatic students (n=1673) Controls = students who were never asthmatic (n=22,109) Boys and girls Elementary and junior high school students Aged 6-15 years, Tokorozawa City, Japan Tokorozawa Childhood Asthma and Pollinosis Study |
Seafood |
|
|
Amount |
Results |
Conclusion** |
|
Fish intake categories: 1 = Almost none 2 = 1-2 times/month 3 = 1-2 times/week 4 = ≥3-4 times/week Serving size unspecified; cited that “most of the variation is explained by frequency of use rather than differences in serving sizes” |
After adjusting for age, gender, parental history of asthma: The OR for current asthma was slightly significantly higher for those who ate fish 1-2 times/week compared to those who ate fish 1-2 times/month (OR=1.133, 95% CI 1.021-1.258); and Although the ORs for current asthma were not significant for those who ate fish almost never (OR=0.957, 95% CI 0.725-1.263) and ≥3-4 times/week (OR=1.334, 95% CI 0.907-1.963) compared to those who ate fish 1-2 times/month, there was a significant positive trend with an increase of fish consumption (p for trend = 0.0078). After adjusting for age, gender, parental history of asthma, and vegetable and fruit intake: The OR for current asthma was slightly significantly higher for those who ate fish 1-2 times/week compared to those who ate fish 1-2 times/month (OR=1.117, 95% CI 1.005-1.241); and Although the ORs for current asthma were not significant for those who ate fish almost never (OR=1.039, 95% CI 0.785-1.376) and ≥3-4 times/week (OR=1.319, 95% CI 0.896-1.943) compared to those who ate fish 1-2 times/month, there was a significant positive trend with an increase of fish consumption (p for trend = 0.0349). |
A |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Hodge et al., 1996* |
Case-control |
Boys and girls (n=468) Aged 8-11 Sydney, Australia With airway hyperresponsiveness, wheeze in the last 12 months, and 3-in-5 sample of children with no airway hyperresponsiveness or wheeze in the last 12 months |
Seafood |
In the past year |
|
Ellwood et al., 2001 |
Ecological |
Children Aged 6-7 and 13-14 years 53 countries The International Study of Asthma and Allergies in Childhood (ISAAC) Data from FAO Food Balance Sheet |
PUFA and seafood intake |
|
|
Amount |
Results |
Conclusion** |
|
Total fish intake/week Ever eat fresh fish, fresh oily fish, or fresh non-oily fish |
There were no significant differences in total fish intake between children with normal airways (1.2 servings, 95% CI 1.0-1.3), airway hyperresponsiveness (1.2 servings, 95% CI 0.9-1.5), wheeze (1.2 servings, 95% CI 0.8-1.5) and current asthma (1.0 servings, 95% CI 0.8-1.2). Significantly fewer children with asthma ever ate oil fish compared to children with normal airways (p<0.05); however, there was no significant difference between those with current asthma and normal children who ate exclusively oily fish. After adjusting for atopy, parental asthma, parental smoking, ethnicity, country of birth, early respiratory illness, and sex: Children who ate oily fish had a significantly lower OR of current asthma when compared to children who did not eat oily fish (OR=0.26, 95% CI 0.09-0.72); and There were no other significant associations found between type of fish (fresh fish, oily fish, non-oily fish) and airway hyperresponsiveness, wheeze, or current asthma. |
B |
|
Percentage of total energy consumed as PUFA: 3%-12% Range of fish intake not reported |
There were no significant associations found between total PUFA intake (% of total fat) for current wheezing, severe wheezing, allergic rhinoconjunctivitis, and atopic eczema. There was a significant inverse association found between all fish (fresh and frozen) consumption and asthma, allergic rhinoconjunctivitis, and atopic eczema, for the 13- to 14-year-old age group; the same inverse association remained for the 6- to 7-year-old age group, but the association was weaker. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
Timing of Exposure |
|
Satomi et al., 1994* |
Ecological |
Boys and girls (n=7742) Aged 6-11 years Japan 1st-, 3rd-, 5th-grade students Coastal schools = fish harvest and consumption are high Inland schools = located far from sea but close to the coast school district |
Seafood |
|
|
*Included in Schachter HM, Reisman J, Tran K, Dales B, Kourad K, Barnes D, Sampson M, Morrison A, Gaboury I, Blackman J. 2004. Health Effects of Omega-3 Fatty Acids on Asthma. Summary, Evidence Report/Technology Assessment No. 91 (Prepared by the University of Ottawa Evidence-based Practice Center under Contract No. 290-02-0021). AHRQ Publication No. 04-E013-2. Rockville, MD: Agency for Healthcare Research and Quality. **N = Evidence of no association or no clear association; B = Evidence of a benefit; A = Evidence of an adverse effect. |
||||
|
Amount |
Results |
Conclusion** |
|
Fish consumption categories: Very often = ≥4-5 times/week Relatively often = 2-3 times/week Often = 1 time/week Infrequently = 1-2 times/month Seldom = <1 time/month |
Coastal school children who ate reddish fish (sardine, mackerel, pike) very often had a significantly lower prevalence of history of asthma than those who seldom ate reddish fish (p<0.01). There were no other significant differences for these children based on consumption of pale fish, shellfish, fish-paste, seaweed, and dried fish. Inland school children who ate pale fish (flatfish, sea bream, turbot) and seaweed very often had significantly higher prevalence of history of asthma than those who seldom ate pale fish and seaweed (p<0.01; 0.01<p<0.05, respectively). There were no other significant differences for these children based on reddish fish, shellfish, fish-paste, and dried fish. |
B |
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Studies on Adult Chronic Diseases
TABLE B-2a Secondary Prevention Studies with Cardiovascular Outcomes
|
Author |
Study Type |
Subjects |
Exposure |
|
Hooper et al., 2006 |
Meta-analysis |
48 randomized controlled trials 41 cohorts Omega-3 intake for ≥6 months in adults Primary and secondary prevention |
n-3 supplement |
|
Amount |
Results |
Conclusion** |
|
High omega-3 fat vs. low omega-3 fat/control Intake differed by 0.1-0.6 g omega-3/day among the two groups (absolute levels not specified) |
Based on RCTs, no significant differences were found between the high omega-3 fat group and the low omega-3 fat/control group with regards to risk of mortality (n=15 RCTs; RR=0.87, 95% CI 0.73-1.03), cardiovascular events (n=18 RCTs; RR=0.95, 95% CI 0.82-1.12), cancer or death from cancer (n=10 RCTs; RR=1.07, 95% CI 0.88-1.30), or stroke (n=9 RCTs; RR=1.17, 95% CI 0.91-1.51). Based on cohorts, no significant differences were found between the high omega-3 fat group and the low omega-3 fat/control group with regards to risk of cardiovascular events (n=7 cohorts; RR=0.91, 95% CI 0.73-1.13), cancer or death from cancer (n=7 cohorts; RR=1.02, 95% CI 0.87-1.19), or stroke (n=4 cohorts; RR=0.87, 95% CI 0.72-1.04). Based on three cohorts, those in the low omega-3 fat/control group had a significantly higher risk of mortality compared to those in the high omega-3 fat group (RR=0.65, 95% CI 0.48-0.88). |
N |
|
Amount |
Results |
Conclusion** |
|
|
Based on RCTs, no significant differences were found between those randomized to n-3 supplementation or advice and those not randomized to n-3 supplementation or advice with regards to total mortality (n=44 RCTs; RR=0.87, 95% CI 0.73-1.03), combined cardiovascular events (n=31 RCTs; RR=0.95, 95% CI 0.82-1.12), cancers (n=10 RCTs; RR=1.07, 95% CI 0.88-1.30), cardiovascular deaths (n=44 RCTs; RR=0.85, 95% CI 0.68-1.06), fatal myocardial infarction (n=38 RCTs; RR=0.86, 95% CI 0.60-1.25), non-fatal myocardial infarction (n=26 RCTs; RR=1.03, 95% CI 0.70-1.50), sudden death (n=37 RCTs; RR=0.85, 95% CI 0.49-1.48), angina (n=25 RCTs; RR=0.78, 95% CI 0.59-1.02), stroke (n=26 RCTs; RR=1.17, 95% CI 0.91-1.51), heart failure (n=20 RCTs; RR=0.51, 95% CI 0.31-0.85), peripheral vascular events (n=17 RCTs; RR=0.26, 95% CI 0.07-1.06), and re-vascularization (n=23 RCTs; RR=1.05, 95% CI 0.97-1.12). Based on cohort studies, no significant differences were found between those randomized to n-3 supplementation or advice and those not randomized to n-3 supplementation or advice with regards to combined cardiovascular events (n=7 cohorts; RR=0.91, 95% CI 0.73-1.13), cancers (n=10 cohorts; RR=1.02, 95% CI 0.87-1.19), nonfatal myocardial infarction (n=4 cohorts; RR=0.93, 95% CI 0.69-1.26), stroke (n=4 cohorts; RR=0.87, 95% CI 0.72-1.04), peripheral vascular events (n=1 cohort; RR=0.94, 95% CI 0.84-1.04), and revascularization (n=2 cohorts; RR=1.07, 95% CI 0.76-1.50). Based on cohort studies, significant differences were found between those randomized to n-3 supplementation or advice and those not randomized to n-3 supplementation or advice with regards to total mortality (n=3 cohorts; RR=0.65, 95% CI 0.48-0.88), cardiovascular deaths (n=11 cohorts; RR=0.79, 95% CI 0.63-0.99), fatal myocardial infarction (n=2 cohorts; RR=0.42, 95% CI 0.21-0.82), and sudden death (n=1 cohort; RR=0.44, 95% CI 0.21-0.91). |
N |
|
Author |
Study Type |
Subjects |
Exposure |
|
Konig et al., 2005 |
Meta-analysis |
7 observational studies (primary prevention) 4 RCTs (secondary prevention) |
Seafood |
|
Burr et al., 2005 |
Review |
Review of two randomized controlled trials (Burr et al., 1989, 2003 below) Secondary prevention |
Dietary advice |
|
Harper and Jacobson, 2005 |
Review |
Systematic literature review of 14 randomized controlled trials Northern Europe, Southern Europe, India Excluded if trial involved >1 intervention unless in a prospective 2×2 design Patients followed for ≥1 year Secondary prevention |
6 on fish oil 2 on fish 5 on ALA suppl. 2 on ALA-enriched diets |
|
Amount |
Results |
Conclusion** |
|
Servings/week, a continuous number 1 serving = 100 g |
Among those with no preexisting CHD (from observational studies), the linear regression model showed that each one serving increase in fish consumption per week reduces one’s risk of CHD death by 0.039 (95% CI −0.066 to −0.011) but does not significantly change one’s risk of nonfatal MI by (ΔRR=0.0083, 95% CI −0.012 to 0.028) “The information available is insufficient for the purposes of quantitatively analyzing the impact of fish consumption on CHD risk for individuals with preexisting CHD” (from RCTs). |
B |
|
See Burr et al., 1989, 2003 below |
“It appeared that fish oil, which protected post-MI male patients in DART, increased the risk of cardiac death in men with angina, being particularly associated with sudden death.” “The apparently conflicting findings may be attributable to the different clinical conditions of the subjects … together with different effects of dietary fish and fish oil.” |
N |
|
|
“The evidence supports a role for fish oil (EPA or DHA) or fish in secondary prevention, because the clinical trials have demonstrated a reduction in total mortality, CHD death, and sudden death.” “Evidence from these trials had indicated that EPA plus DHA supplementation in the range of 0.5-1.8 g/day provides significant benefit.” “The data on the plant-based n-3 PUFA, ALA, is very promising. However, the existing studies were small, and a large randomized controlled trial is needed before recommendations can be definitely made for CHD prevention.” “The data for ALA show possible reductions in sudden death and nonfatal myocardial infarction, suggesting other potential cardioprotective mechanisms other than a predominately antiarrhythmic role.” |
B |
|
Author |
Study Type |
Subjects |
Exposure |
|
Leaf et al., 2005 |
Randomized Controlled Trial |
Men and women (n=402) Mean age about 65 years 18 US centers Had a cardioverter defibrillator implanted because of a history of cardiac arrest, sustained ventricular tachycardia, or syncope with inductive, sustained ventricular tachycardia or ventricular fibrillation during electrophysiologic studies Follow-up of 12 months Secondary prevention |
n-3 supplement |
|
Amount |
Results |
Conclusion** |
|
Treatment: Four 1 g gelatin capsules of an ethyl ester concentrate of n-3 fatty acids (2.6 g EPA+DHA) Placebo: Four 1 g capsules of olive oil |
After controlling for sex, left ventricular ejection fraction (continuous), New York Heart Association class III congestive heart failure, history of myocardial infarction, history of prior defibrillator therapies for ventricular tachycardia or ventricular fibrillation, time from implanted cardioverter/defibrillator implant (continuous), and sustained ventricular tachycardia as the indication for the implanted cardioverter defibrillator: The intent-to-treat analysis provided a significant relative risk of time to first event of 0.67 (95% CI 0.47-0.95, p=0.024) for all confirmed events among those in the treatment group compared to the placebo group; The on-treatment analysis (for all who had taken any of their prescribed supplements) provided a significant relative risk of time to first event of 0.67 (95% CI 0.46-0.98, p=0.037) for all confirmed events among those in the treatment group compared to the placebo group; and The on-treatment analysis (for all on-treatment at least 11 months) provided a significant relative risk of time to first event of 0.52 (95% CI 0.32-0.83, p=0.0060) for all confirmed events among those in the treatment group compared to the placebo group. Similar results were found when probable events were also included. |
B |
|
Author |
Study Type |
Subjects |
Exposure |
|
Raitt et al., 2005 |
Randomized Controlled Trial |
Men and women (n=200) Mean age about 62 Patients at six medical centers in the United States Receiving an implantable cardioverter defibrillator for an electrocardiogram-documented episode of sustained ventricular tachycardia or ventricular fibrillation that was not the result of acute myocardial infarction or a revisible cause or who had a preexisting implantable cardioverter defibrillator and had received implantable cardioverter/defibrillator therapy for an electrocardiogram-documented episode of sustained ventricular tachycardia or ventricular fibrillation within the last 3 months No class I or class II antiarrhythmic medications; ≥1 fatty fish meal/week; flaxseed oil, cod-liver oil, or fish-oil supplements in the last month Follow-up of 2 years Secondary prevention |
n-3 supplement |
|
Amount |
Results |
Conclusion** |
|
Treatment: 1.8 g/day fish oil (42% EPA and 30% DHA) Placebo: Olive oil (73% oleic acid, 12% palmitic acid, 0% EPA+DHA) |
There was a significant difference in the number of patients hospitalized for neurological conditions among those assigned to the placebo compared to those assigned to the treatment (p=0.04). However, there were no other significant differences found in mortality, hospitalizations, coronary revascularization, myocardial infarction, cancer, and diarrhea between the two groups. There were no significant differences in the time to first episode of implantable cardioverter/defibrillator therapy for ventricular tachycardia or ventricular fibrillation after randomization between the two groups (p=0.19). However, among those with qualified arrhythmia at the time of study entry, those assigned to fish oil had significantly greater incidence of ventricular tachycardia or ventricular fibrillation treated by the implantable cardioverter defibrillator compared to those assigned to placebo (p=0.007). |
A |
|
Author |
Study Type |
Subjects |
Exposure |
|
Baer et al., 2004 |
Randomized Crossover Trial |
Men (n=50) Aged 25-60 years All races Beltsville, MD In good health, with no hypertension, hyperlipidemia, diabetes, peripheral vascular disease, gout, liver or kidney disease, or endocrine disorders Fasting plasma HDL-c >0.65 mmol/L, triacylglycerol <3.39 mmol/L, and 85-120% of their sex-specific ideal BMI No lipid-lowering drugs, blood pressure medication, or dietary supplements, or eating habits inconsistent with the study protocol 30-week intervention (six diets for 5 weeks each) Primary prevention |
Diet |
|
Amount |
Results |
Conclusion** |
|
Diets 1-5: 38.9% energy from fat, 15% energy from protein, 46.1% energy from digestible carbohydrates Diet 6: 30.4% energy from fat, 54.6% energy from carbohydrate Diet 1 (carbohydrate diet): 8.5% of energy from fat replaced by digestible carbohydrate Diet 2 (oleic acid diet): 8% of energy enriched with oleic acid Diet 3 (LMP diet): 8% of energy enriched with lauric (L), myristic (M), and palmitic (P) acids Diet 4 (stearic acid diet): 8% of energy enriched with stearic acid Diet 5 (trans fatty acid diet): 8% of energy enriched with trans fatty acids Diet 6 (trans fatty acid + stearic acid diet): 4% energy enriched with trans fatty acids and 4% of energy enriched with stearic acid |
After 5 weeks on the stearic acid diet, the least squares mean plasma fibrinogen levels were significantly higher than after 5 weeks on all other diets (p<0.05). After 5 weeks on the trans fatty acid diet, the least squares mean plasma C-reactive protein levels were significantly higher than after 5 weeks on all other diets (p<0.05). After 5 weeks on the oleic acid diet, the least squares mean plasma interleukin 6 levels were significantly lower than after 5 weeks on all other diets, except for the trans fatty acid + stearic acid diet (p<0.05). After 5 weeks on the trans fatty acids diet, the least squares mean plasma C-reactive protein levels were significantly higher than after 5 weeks on the carbohydrate diet, the oleic diet, and the trans fatty acid + stearic acid diet (p<0.05). After 5 weeks on the oleic acid diet, the least squares mean plasma interleukin 6 levels were significantly lower than after 5 weeks on the trans fatty acid diet, stearic acid diet, or the LMP diet (p<0.05). After 5 weeks on the oleic acid diet, the least squares mean plasma E-selectin levels were significantly lower than after 5 weeks on all other diets, except for the carbohydrate diet (p<0.05). After 5 weeks on the trans fatty acids diet, the least squares mean plasma E-selectin levels were significantly higher than after 5 weeks on all other diets (p<0.05). There were no other significant differences reported between the diets with regards to fibrinogen, C-reactive protein, interleukin 6, or E-selectin levels. |
N |
|
Author |
Study Type |
Subjects |
Exposure |
|
Burr et al., 2003 |
Randomized Controlled Trial |
Men (n=3114) Aged <70 years South Wales, UK Being treated with angina Mortality ascertained at 3-9 years after enrollment No exertional chest pain or discomfort; men awaiting coronary artery by-pass surgery, men who already ate oily fish twice a week, men who could not tolerate oily fish or fish oil, men who appeared to be unsuitable on other grounds (e.g., other serious illness, likelihood of moving out of area) The Diet and Angina Randomized Trial (DART 2) Follow-up of 3 years (after last subject was recruited) Secondary prevention |
Dietary advice |
|
Amount |
Results |
Conclusion** |
|
Fish advice = eat at least 2 portions of oily fish each week or take up to 3 g of fish oil as a partial or total substitute Fruit/vegetable advice = eat 4-5 portions of fruit and vegetables and drink at least 1 glass of natural orange juice daily, and also increase the intake of oats Both = a combination of both of these forms of advice Sensible eating = non-specific advice that did not include either form of advice |
Those given fish advice had significantly higher percentage of cardiac deaths (p=0.02) and sudden deaths (p=0.02) compared to those who did not receive fish advice. There was not a significant difference in the number of total deaths between these two groups. No significant differences were found between the fruit/vegetable advice group and the no fruit/vegetable advice group for total number of deaths, number of cardiac deaths, or number of sudden deaths. After adjusting for age, smoking, previous MI, history of high blood pressure, diabetes, BMI, serum cholesterol, medication, and fruit advice or fish advice: Those who received fish advice had a slightly significant higher hazard ratio for cardiac deaths (HR=1.26, p=0.047) and a significant higher hazard ratio for sudden death (HR=1.54, p=0.025), compared to those who did not receive fish advice. There were no significant associations found between those who received fruit/vegetable advice vs. those who did not and all deaths, cardiac deaths, or sudden deaths. |
A |
|
Author |
Study Type |
Subjects |
Exposure |
|
Marchioli et al., 2002 |
Randomized Controlled Trial |
Men and women (n=11,323) No age limits Gruppo Italiano per lo Studio della Sopravivivenza nell’Infarto miocardico-Prevenzione (GISSI trial) Recent MI Follow-up of 3.5 years (about 38,418 person-years) Secondary prevention |
n-3 supplement |
|
Amount |
Results |
Conclusion** |
|
n-3 fatty acids group = 1 g/day Vitamin E group = 300 mg/day Combination group Control group |
After adjusting for age, sex, complications after myocardial infarction, smoking habits, history of diabetes mellitus and arterial hypertension, total blood cholesterol, HDL cholesterol, fibrinogen, leukocyte count, and claudication intermittens: Those who received n-3 fatty acids had a significantly lower relative risk of death, nonfatal MI, and nonfatal stroke at 9 months, 12 months, and 42 months of follow-up than the controls (RR=0.76, 95% CI 0.60-0.97 at 9 months, RR=0.79, 95% CI 0.63-0.98 at 12 months, and RR=0.85, 95% CI 0.74-0.98 at 42 months). The relative risks at 3 and 6 months of follow-up were also lower in the n-3 fatty acid group compared to the controls, but they were not significant. Those who received n-3 fatty acids had a significantly lower relative risk of CVD death, nonfatal MI, and nonfatal stroke at 9 months (RR=0.75, 95% CI 0.58-0.97), 12 months (RR=0.78, 95% CI 0.62-0.99), and 42 months (RR=0.80, 95% CI 0.68-0.94) of follow-up than the controls. The relative risks at 3 and 6 months of follow-up were also lower in the n-3 fatty acid group compared to the controls, but they were not significant. |
B |