Weight Gain During Pregnancy: Reexamining the Guidelines (2009)

The purpose of this systematic evidence-based review, requested by the Agency for Healthcare Research and Quality (AHRQ) and conducted by the RTI International—University of North Carolina at Chapel Hill Evidence-based Practice Center (RTI-UNC EPC), was to review the evidence on outcomes of gestational weight gain with specific attention to five key questions:

• KQ 1. What is the evidence that either total weight gain or rate of weight gain during pregnancy is associated with (1) birth outcomes, (2) infant health outcomes, and (3) maternal health outcomes? Does any evidence suggest that either total weight gain or rate of weight gain is a causal factor in infant or maternal health outcomes?

• KQ 2. What are the confounders and effect modifiers for the association between gestational weight gain (overall and patterns) and birth outcomes? Based on the findings in KQ 1, do these confounders and effect modifiers themselves contribute to antepartum or postpartum complications or to longer-term maternal and fetal complications, including development of adult obesity?

• KQ 3. What is the evidence that weight gains above or below thresholds defined in the 1990 IOM body mass index (BMI) guide-

lines or weight loss in pregnancy contribute to antepartum or postpartum complications or longer-term maternal and fetal complications? How do these relationships vary by sociodemographic characteristics (i.e., race and age)?

• KQ 4. What are the harms or benefits of offering the same weight gain recommendations to all pregnant women, irrespective of age and body weight considerations (e.g., pregravid weight, actual body weight at a particular time point, or optimal body weight)?

• KQ 5. What are the anthropometric tools for determining adiposity and their appropriateness for the pregnancy state? What are the risks and benefits of measuring adiposity for (1) clinical management of weight gain during pregnancy and (2) evaluation of the relationship between weight gain and outcomes of pregnancy?

The review focused on screening studies from 1990 to October 2007 that were published in English, and excluded studies with low sample size (case series < 100 and cohorts < 40) or failure to control for pregravid weight. In total, 150 studies were systematically reviewed and each was rated on quality and used to assess the strength of evidence for each outcome. The report, including appendices and evidence tables, can be accessed and viewed in its entirety at http://www.ahrq.gov/clinic/tp/admattp.htm. Literature published outside of the scope of the report (prior to 1990 and after October 2007) are reviewed in Appendix C of this report. The methods and results and of the evidence review (Chapter 3 of the report) are provided below.

In this chapter, we document the procedures that the RTI International-University of North Carolina Evidence-based Practice Center (RTI-UNC EPC) used to develop this comprehensive evidence report on outcomes of maternal weight gain. The team was led by a senior health services researcher (Meera Viswanathan, PhD, Study Director), a senior epidemiologist (Anna Maria Siega-Riz, PhD, RD, Scientific Director), and a senior nurse-researcher (Merry-K Moos, FNP, MPH, co-Scientific Director).

We first describe our strategy for identifying articles relevant to our five key questions (KQs), our inclusion and exclusion criteria, and the process we used to abstract relevant information from the eligible articles and generate our evidence tables. We also discuss our criteria for grading the quality of individual articles and for rating the strength of the evidence as a whole. Finally, we explain the peer-review process.

Our inclusion and exclusion criteria are documented in Table 1. As noted in Chapter 1, this systematic review focuses on outcomes of maternal weight gain with respect to the 1990 recommendations from the Institute of Medicine (IOM). Largely for that reason, we limited our searches to articles published in 1990 and thereafter. We also restricted our searches to developed countries so that we could have data generally relevant for maternal weight gain and health outcomes in the United States.

We excluded studies that (1) were published in languages other than English (given the available time and resources); (2) did not report information pertinent to the key clinical questions; (3) had fewer than 40 subjects

for randomized controlled trials (RCTs) or nonrandomized cohorts with comparisons or fewer than 100 subjects for case series; and (4) were not original studies.

For KQ 1, 2, 3, and 4, we required that the reported association between maternal weight gain and health outcomes accounted for prepregnancy body mass index (BMI) or weight, either through stratified univariate analysis or multivariate analysis.

Databases We used multifaceted search strategies to include current and valid research on the KQs, which we applied to four standard electronic databases—MEDLINE^®, Cochrane Collaboration resources, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Embase. We also hand-searched the reference lists of relevant articles to make sure that we did not miss any relevant studies. We consulted with our Technical Expert Panel (TEP) about any studies or trials that are currently under way or that may not yet be published.

Search terms. Based on the inclusion/exclusion criteria above, we generated a list of Medical Subject Heading (MeSH) search terms (Table 2 and Appendix A*). Our TEP also reviewed these terms to ensure that we were not missing any critical areas, and this list represents our collective decisions as to the MeSH terms used for all searches.

Our searches in MEDLINE^® produced 715 unduplicated records. Searches in other databases yielded in 190 new records from CINAHL and 4 from Embase. Similar searches in Cochrane did not produce any new citations. Following an update on October 3, 2007, and additional searches for KQ 5, we ultimately identified 1,082 unduplicated records. In addition, peer reviews suggested 3 new citations that met our inclusion criteria.

Figure 1 presents the yield and results from our searches, which we conducted from February through October 3, 2007. Beginning with a yield

FIGURE 1. Disposition of articles for gestational weight gain.

of 1,085 articles, we retained 150 articles that we determined were relevant to address our KQs and met our inclusion/exclusion criteria (Table 1). We reviewed titles and abstracts of the articles against the basic inclusion criteria above; we retained relevant articles, all published after our search cutoff date of January 1990, and used them as appropriate in the discussion in Chapter 4.

Article selection process Once we had identified articles through the electronic database searches, review articles, and reference lists, we examined abstracts of articles to determine whether studies met our criteria. Each abstract was independently, dually reviewed for inclusion or exclusion, using an Abstract Review Form (Appendix B). If one reviewer concluded that the article should be included in the review, we retained it.

Of this entire group of 1,085 articles, 479 required full review. For the full article review, one team member read each article and decided whether it met our inclusion criteria, using a Full Text Inclusion/Exclusion Form (Appendix B*). Reasons for article exclusion are listed in Appendix D.

The senior staff who conducted this systematic review jointly developed the evidence tables. We designed the tables to provide sufficient information to enable readers to understand the studies and to determine their quality; we gave particular emphasis to essential information related to our KQs. We based the format of our evidence tables on successful designs that we have used for prior systematic reviews.

We trained abstractors by having them abstract several articles into evidence tables and then reconvening as a group to discuss the utility of the table design. The abstractors repeated this process through several iterations until they decided that the tables included the appropriate categories for gathering the information contained in the articles.

Three junior epidemiologists (Sunni Mumford, SM; Andrea Deierlein, MS, MPH; and Julie K. Knaack, MPH, RD, LDN) shared the task of initially entering information into the evidence tables. Senior staff reviewed the articles and edited all initial table entries for accuracy, completeness, and consistency. Abstractors reconciled all disagreements concerning the information reported in the evidence tables. The full research team met regularly during the article abstraction period and discussed global issues related to the data abstraction process.

The final evidence tables are presented in their entirety in Appendix C. Studies are presented in the evidence tables alphabetically by the last name

of the first author. A list of abbreviations and acronyms used in the tables appears at the beginning of that appendix.

The evidence for this systematic review is based almost entirely on observational studies. This fact presents a challenge for rating individual studies. Quality rating forms for RCTs have been validated and in use for several years; a similarly well-validated form for observational studies does not exist.

Thus, as a parallel effort, we developed a form to rate observational studies.³⁵ This form, which can be used to rate the quality of a variety of observational studies, was based on a review of more than 90 AHRQ systematic reviews that included observational studies; we supplemented this review with other key articles identifying domains and scales.^36,37 We structured the resultant form largely on the basis of the domains and subdomains suggested by Deeks and colleagues;³⁶ we then adapted it for use in this systematic review (Appendix B*).

The form currently includes review of nine key domains: background, sample selection, specification of exposure, specification of outcome, soundness of information, followup, analysis comparability, analysis of outcome, and interpretation. Each of these domains was further evaluated on aspects of quality of the study design or reporting that would influence the reader’s perception of internal validity of the journal article (Table 3). We note that variations in reporting could result in different scores for studies drawing from the same sample.

As described in Table 3, we combined these elements to generate overall scores. We set the default as fair and then focused on the threshold required for good and poor studies; the algorithm is also described in Table 3. Fair studies, therefore, include studies that were predominantly fair (four to nine fair ratings on domains) and could not be rated either good (fewer than five good ratings for subdomains) or poor (fewer than three poor ratings for subdomains). Studies with more than five good ratings for domains that also received one or two poor ratings were downgraded to fair quality.

Key methodological concerns in this literature relate to the source of information on weight gain and the timing of measurement of weight gain. Studies that relied solely on self-reported pregravid and final pregnancy weights suffer from well-documented issues of recall bias. In addition, women tend to misreport their weight, and this bias varies by weight status³⁸ and ethnicity.³⁹ The timing of weight measurement (for pregravid weight and final weight) can vary depending on the design of the study; when unreported, the total weight gain during pregnancy cannot be assumed to be collected at similar time points for all women within the study,

resulting in further bias. Our rating algorithm, therefore, paid special attention to the source of data on gestational weight gain and the timing of measurement. Studies that relied solely on recalled prepregnancy and total pregnancy weight were rated poor on that domain, but if they defined their gestational weight variable clearly (providing details on the timing of measurement for pregravid and final weight measurements) and either checked for the biological plausibility of pregravid weight status or explained how outliers were dealt with, they could receive an overall fair rating (assuming that they received fewer than three poor ratings overall).

Our scheme follows the criteria applied in an earlier RTI-UNC EPC systematic review of systems for rating the strength of a body of evidence.⁴⁰ That system has three domains: quality of the research (as evaluated by the quality rating algorithm described above), quantity of studies (including number of studies and adequacy of the sample size), and consistency of findings. Two senior staff members assigned grades by consensus.

We graded the body of literature for each KQ and present those ratings as part of the discussion in Chapter 4. The possible grades in our scheme are as follows:

1. Strong: The evidence is from studies of sound design (good quality); results are both clinically important and consistent with minor exceptions at most; results are free from serious doubts about generalizability, bias, or

flaws in research design. Studies with negative results have sufficiently large samples to have adequate statistical power.

2. Moderate: The evidence is from studies of sound design (good quality), but some uncertainty remains because of inconsistencies or concern about generalizability, bias, research design flaws, or adequate sample size. Alternatively, the evidence is consistent but derives from studies of weaker design (fair quality).

3. Weak: The evidence is from a limited number of studies of weaker design (fair or poor quality). Studies with strong design (good quality) either have not been done or are inconclusive.

4. No evidence: No published literature.

As is customary for all evidence reports and systematic reviews done for AHRQ, the RTI-UNC EPC requested review of this report from a wide array of individual outside experts in the field, including our TEP, and from relevant professional societies and public organizations. AHRQ also requested review from its own staff. We sent 20 invitations for peer review: 6 TEP members, 6 relevant organizations, and 8 individual experts. Reviewers included clinicians (e.g., obstetrics and gynecology, women’s health/general health), representatives of federal agencies, advocacy groups, and potential users of the report.

We charged peer reviewers with commenting on the content, structure, and format of the evidence report, providing additional relevant citations, and pointing out issues related to how we had conceptualized and defined the topic and KQs. We also asked them to complete a peer review checklist. We received comments from 11 of the invited peer reviewers in addition to comments from AHRQ staff. The individuals listed in Appendix E** gave us permission to acknowledge their review of the draft. We compiled all comments and addressed each one individually, revising the text as appropriate.

This chapter presents the results of our evidence review for the following four key questions (KQs): KQ 1, outcomes of gestational weight gain; KQ 3, outcomes of gestational weight gain within or outside the recommendations of the Institute of Medicine (IOM); and KQ 5, anthropometrics of gestational weight gain.

We note that KQ 2, on modifiers of outcomes, is derivative of KQ 1. KQ 4, on recommendations for weight gain, is derivative of KQ 3. Because we framed KQ 2 and KQ4 as synthesis questions, we cover them in Chapter 4.

Appendix C provides the detailed evidence tables for KQs 1, 3, and 5. Our summary tables below feature groups of studies addressing each outcome; we present these text tables only when we have three or more studies pertaining to that particular outcome. These tables are organized by quality (good, then fair, then poor), and then alphabetically.

The summary tables generally provide information to identify the study (author and date), sample size, study quality, definition of gestational weight gain, definition of outcome, results, and confounders and effect modifiers. Unless otherwise noted, we use the metrics (e.g., grams, kilograms, pounds) that each study article used; we did not recalculate measures into the same metric.

We present outcomes in the physiological order, beginning with maternal antepartum and intrapartum outcomes, then birth outcomes (neonatal outcomes at the time of birth), infant outcomes (< 1 year), child outcomes (≥ 1 year), and finally maternal short- and long-term outcomes. Evidence Tables 1-35 (Appendix C) include studies relevant for KQ 1, listed alphabetically by author. For each outcome, we describe study characteristics and then report an overview of results, followed by detailed results. When meaningful, we present results separately for varied measures of gestational weight gain (categorical measures of weight gain, rate of weight gain, total weight gain, and other). For some bodies of evidence, variations in the definition of the outcome and inconsistencies in the direction of effect may suggest that an overall assessment of the effect is more meaningful than separate assessments of outcomes associated with each measure of gestational weight gain. Summary tables and text include information on the confounders and effect modifiers accounted for in each study.

Study characteristics Five studies (Evidence Table 1) investigated the relationship between weight gain and diverse maternal discomforts of pregnancy: a composite of pregnancy discomforts,⁴¹ physical energy and fatigue,⁴² stretch marks,^43,44 and heartburn.⁴⁵

Overview of results Two fair^41,42 and three poor studies^43-45 found no differences for women who gained an excessive amount of weight compared to those who did not, irrespective of body mass index (BMI) group,⁴² a higher frequency of symptoms from midpregnancy through the 36th week of gestation,⁴⁶ no association between gestational weight gain

and heartburn in gestation,⁴⁵ and some increased risk of stretch marks with increased weight gain.^43,44

Detailed results A prospective cohort study in Sweden examined symptoms across pregnancy and attempted to document the prevalence and frequency of 27 pregnancy symptoms while controlling for biomedical factors.⁴¹ A cohort of 476 nulliparous women was assessed six times during gestation (gestational ages of 10, 12, 20, 28, 32, and 36 weeks). The investigators sought to determine the prevalence of various symptoms in pregnancy and to explore whether psychosocial variables are explanatory while controlling for possible confounding variables such as medical risk, smoking, and weight gain. Pregravid BMIs were calculated from self-reported weight information and women were weighed when they arrived at the hospital to give birth. Total weight gain was associated with a higher frequency of symptoms from midpregnancy through the 36th week of gestation. Reflecting on their findings, the researchers recommend that weight gain be included in future studies exploring the etiology of symptoms during pregnancy.

A secondary analysis of data collected in a US prospective cohort study investigated the relationship of prepregnancy weight and gestational weight gain on levels of physical energy and physical symptoms collected through a series of questionnaires that had been administered in patient homes in early, mid, and late pregnancy.⁴² All weight data were self-reported. The researchers found no differences in the number of physical symptoms or level of physical energy reported by women who gained an excessive amount of weight compared with those who did not, irrespective of BMI group. Women whose weight gain was greater than the IOM guidelines reported a lower level of functional status in the third trimester than women whose weight gain was within the guidelines (P = 0.014). Women participating in this study were 30.9 years of age on average, married, English-speaking, and of low medical risk. No confounders or effect modifiers were accounted for in the analysis.

The one study (rated poor quality) that investigated the determinants of heartburn in pregnancy undertook a cross-sectional study in the United Kingdom of 602 women of different gestational lengths who self-reported their pregravid weight and completed a questionnaire.⁴⁵ The analysis, which considered age, race, parity, and pregravid BMI, found that weight gain in pregnancy was not a risk factor for heartburn in gestation.

Two studies (both rated poor quality) reported on the relationship between stretch marks (striae gravidarum) and weight gain.^43,44 One was a small retrospective cohort (N = 48) recruited from one private and one teaching hospital in the United States.⁴³ Mean total weight gain was significantly greater in women with abdominal striae than women without stretch

marks (P < .05) but the analysis did not account for any confounders or effect modifiers. The other study reported on a cross-sectional sample of 324 primiparous women who were assessed within 48 hours of giving birth in Great Britain.⁴⁴ Logistic regression analysis found maternal age, BMI, weight gain, and neonatal birthweight to be independently associated with striae. Weight gain was a weakly significant risk factor (OR, 1.08; 95% CI, 1.02-1.14).

Study characteristics A retrospective cohort study compared the experiences of 1,270 women who had an antepartum admission before 24 weeks of gestation for hyperemesis with those of 154,821 women who experienced no antepartum admission related to vomiting (Evidence Table 2).⁴⁷ Baseline weight and weight gain were abstracted from the Nova Scotia Atlee Perinatal Database, but the authors did not explain how the weights entered into the database were assessed.

Overview of results One poor study found a correlation between increasing likelihood of total gestational weight gain of < 7 kg with increasing numbers of antenatal admissions for hyperemesis.⁴⁷

Detailed results The study, undertaken to determine the relationship between hyperemesis and a variety of outcomes, used the number of antenatal admissions as a marker for severity of disease. The study found a correlation between increasing likelihood of total gestational weight gain of < 7 kg with increasing numbers of antenatal admissions. Many potential confounders were incorporated into the analysis including previous pregnancy experiences, psychiatric disorders, pregravid weight, and preexisting medical diseases. Weight gain information, however, was missing for approximately 17 percent of the cohort.

Study characteristics Eleven studies specifically investigated the relationship between weight gain in pregnancy and the development of abnormal glucose metabolism (Evidence Table 3, Table 4).^3,48-57 Of these, four were done outside the United States.^49,50,52,53 Numerous inconsistencies in methodology and definitions, such as differences in criteria used for the diagnosis of gestational diabetes mellitus (GDM), preclude clear summations regarding the research.

The diagnostic algorithm for assigning the diagnosis of GDM in most asymptomatic women begins with administration and interpretation of a 1-hour glucose challenge test; those women who have a glucose level following the challenge above a specified level then receive a 3-hour glucose

tolerance test (GTT). Abnormalities in the GTT results are considered diagnostic of GDM. The set point for determining if the glucose challenge test is abnormal is not universally agreed upon. Therefore, more women in one setting may be tested for disease than in another setting, not because of an increased prevalence of disease but because of differing definitions of abnormal. In addition, impaired glucose tolerance (IGT) is not clearly defined. Women with an abnormal glucose challenge test who subsequently have a normal GTT are sometimes identified as having IGT; more commonly, women who have one abnormal value in their GTT are designated as having IGT. The lack of standardization in the criteria necessary to be considered to have IGT and GDM hampers the body of research exploring the relationship between weight gain and abnormal glucose tolerance in pregnancy. Further hampering understanding of the relationship is that GDM is generally diagnosed around 28 weeks of gestation and is treated, in part, by dietary counseling and efforts to control weight gain. Similar attention is not directed toward women without this diagnosis. Therefore, using total weight gain as a predictor of disease or as a comparison point to a population without the diagnosis is likely to result in methodologically flawed conclusions.

Overview of results Four studies (1 good,³² fair,^55,56 1 poor⁵¹) found that greater weight gains in pregnancy were positively associated with abnormal glucose tolerance. Three studies (1 good quality,⁴⁸ 1 fair,⁵³ 1 poor⁴⁹) found that women having lower than average weight gains had higher likelihood of GDM. Finally, four studies (2 poor,^50,54 1 fair^52,53,57) found no significant association.

Detailed results Whether total weight gain or the distribution of the gain across trimester or weeks of pregnancy predicts development of GDM is unclear from the articles we reviewed. As previously noted, treatment of the condition can alter total weight gain. Three studies^3,56,57 analyzed the association between weight gain in the first two trimesters of pregnancy and the diagnosis of GDM. A good-quality study reported that a weight gain ratio at the end of the second trimester of pregnancy that was greater than the IOM recommendations correlated with abnormalities of glucose metabolism.³ A fair study found no correlation between weight gain in the first 24 to 28 weeks of gestation and an abnormal glucose challenge test, the first step in the testing process to identify GDM.⁵⁷ A third study assessed to be of fair quality reported that weight gain in the first 28 weeks of gestation was a significant predictor of the diagnosis of GDM (OR, 1.02; 95% CI, 1.004-1.042; P = 0.015) for their total sample of 987 black and Latina women but that total weight gain was not.⁵⁶ The OR for black women was the same (1.02; 95% CI, 1.002-1.044; P = 0.30). However, the

range of weight gain included in the reference category was large (14-28 pounds) especially given that nearly 50 percent of the sample entered into the reported pregnancies with BMIs > 26.0.

Overall, family history of diabetes,^50,56 maternal age,^3,50,56 parity,⁵⁰ and BMI^3,50,56,57 were found to be more predictive of abnormal glucose metabolism than gestational weight gain in the research we reviewed.

Study characteristics Twelve studies investigated the relationship between weight gain and pregnancy-induced hypertensive disorders (Evidence Table 4, Table 5).^{4,25,49,51-55,58-61} Six of the studies were conducted outside the United States;^{49,52,53,58,59,61} six studied US cohorts.^{4,25,51,54,55,60} While all of these studies reported on blood pressures that became elevated during gestation, the criteria for diagnosing gestational hypertension (also called pregnancy-induced hypertension) and preeclampsia were often poorly defined; in addition, criteria for the various diagnoses lacked consistency between studies.

Overview of results The vast majority of the studies (7 fair,^{4,25,53,55,58-60} 3 poor,^49,51,61) found that increasing weight gain was associated with increasing likelihood of a pregnancy-induced hypertensive disorder. Two studies, one fair⁵² and one poor,⁵⁴ did not support this association.

Detailed results Six studies specifically examined the impact of weight gain on the development of pregnancy-induced hypertension in women classified as obese by their pregravid weight status.^{4,49,54,55,58,59} A prospective cohort study from Sweden examined the relationship of weight gain by pregravid BMI on pregnancy outcomes for 245,526 women who delivered term infants between 1994 and 2002.⁵⁸ When compared to a reference gain of 8-16 kg, the researchers found that gains of less than 8 kg were protective against the development of preeclampsia for all pregravid BMI categories. The finding was not significant, however, for those with BMIs < 20. Gaining more than 16 kg increased the likelihood of developing preeclampsia, especially for women who entered pregnancy with lower BMIs. The greatest increased risk was for women entering pregnancy at a BMI of 20 to 24.9 (OR, 2.31; CI, 2.15-2.49); the lowest increased risk was for women who entered pregnancy at a BMI ≥ 35 (OR, 1.50; CI, 1.17-1.92).

One US retrospective cohort study studied 771 women with BMIs of 30 or greater matched by race or ethnicity, delivery date, age categories, and parity categories with women of normal pregravid BMIs (19.8-26.0).⁵⁵ For women of normal weight, as weight increased the prevalence of preeclampsia steadily increased (P = .048) but increasing weight was not associated with the prevalence of gestational hypertension. For obese women, weight

gain and the development of either gestational hypertension or preeclampsia were not significantly associated.

In a retrospective cohort study of 603 Cree women in Canada (rated poor quality), Brennand et al.⁴⁹ found that overweight and obese women had a significant unadjusted OR of 2.25 to 4.25 times higher, respectively, than normal weight women for pregnancy-induced hypertension and 1.25 to 3.45 times higher for preeclampsia.

Three retrospective cohorts were limited to women who entered pregnancy with BMIs ≥ 30.^4,54,59In a study of 481 Danish women, the authors,

using < 5 kg as the reference weight gain, found a statistically significant trend for development of pregnancy-associated hypertension with increasing weight (P = 0.0001).⁵⁹ A U.S. study examined birth certificate data for 120,251 obese women classified according to the 1998 National Institute of Health obesity classes.⁴ The researchers found that the amount of weight gain associated with minimal risk for preeclampsia differed by class of obesity but that, in all classes, a gain of less than 15 pounds was protective. The third study (rated poor quality) specifically investigated pregnancy and neonatal risks associated with BMIs > 35 in 527 morbidly obese women.⁵⁴

Although these women were more likely to experience obstetrical complications than a control population (BMIs 19-27), gestational weight gain did not affect the complication rate.

One other study did not support the association between weight gain and pregnancy-induced hypertension.⁵² In this study, 633 Japanese women who gave birth to a singleton infant at 24-42 weeks of gestational age were studied. Pregravid BMI categories were those defined by the IOM. At the time of the study (2005) the Japan Society of Obstetrics and Gynecology did not have a recent guideline for weight gain during pregnancy; as a result, researchers used the frequency distributions from their population to set quartiles regarding weight gain and then set the parameters for insufficient and excessive gains accordingly. In this study, insufficient gain was defined as less than 8.5 kg and excessive gain as 12.5 kg. Finding no significant influence on weight gain and various perinatal outcomes of the mother or infant, the research team used other cut-off points and was still unable to find an appropriate criterion for predicting risk. The authors stated that their sample size was not sufficient to prove a lack of significance. Of note, the mean pregravid BMI of the sample was 20.9 ± 2.8 and the mean weight gain was 10.5 kg ± 3.4. While this study was assessed to be of fair quality, it has little, if any, generalizability to the United States because our population of childbearing women is more racially and ethnically diverse and have a higher mean BMI.

Study characteristics Two studies reported on the relationship between weight gain in pregnancy and cholelithiasis (gallstones)^62,63 (Evidence Table 5).

Overview of results Two studies (1 poor⁶² and 1 fair⁶³) suggest a potential relationship between weight gain and cholelithiasis.

Detailed results One study reported on weight and the development of gallstones in a prospective study of 128 northern plains Native American and white women in 2004.⁶³ Nine independent variables including BMI, prenatal weight gain, prenatal physical activity, dietary fat, iron supplementation, age, parity, history of gallbladder disease, and serum cholesterol were analyzed. Weight assessments during pregnancy were carefully collected; how pregravid weights were determined is not specifically stated. Gestational weight gain had a nonsignificant, partial correlation of 0.09 and a beta coefficient of 0.13. A case-control study (rated poor quality), using data abstracted from birth certificates, reported on 6,211 women from the state of Washington who had a gallstone-related diagnosis at delivery or in the first year postpartum between 1987 and 2001.⁶² Four controls

were randomly selected for each case and matched for year of delivery. Multiple logistic regression found an inverse relationship between gestational weight gain and gallbladder disease. The OR per kg was. 0.98 (95% CI, 0.97-0.99; P = < 0.001). Maternal age, race, BMI based on self-reported pregravid weight, GDM, and infant gestational age were accounted for in the analysis.

Study characteristics Investigators explored the relationship of gestational weight gain and the risks for premature rupture of membranes (PROM) in two studies (Evidence Table 6).^64,65 One involved a total of 1,176 women who had experienced preterm delivery, defined as gestation ≤ 36 weeks, with PROM (n = 220), preterm delivery without PROM (n = 184), full-term delivery with PROM, defined as gestation ≥ 37 weeks, with at least 3 hours of PROM before the onset of labor, (n = 184), and 588 controls. Women were recruited following delivery at two academic medical centers in the United States.⁶⁴ In another study,⁶⁵ the investigators analyzed data for 62,167 women enrolled in the Danish National Birth Cohort who had pregravid weight and total weight gain recorded in the registry. They assessed the impact of obesity and gestational weight gain on the risk of various subtypes of preterm birth, including PROM. Pregravid weight and gestational gains were self-reported.

Overview of results Two fair studies^64,65 suggest that low weight gain (< 21 pounds) or low rate of weight gain (< 275 g per week) is associated with a higher risk of PROM for full-term pregnancies and preterm pregnancies.

Results for categorical measures of weight gain. A retrospective case-control study,⁶⁴ published in 1992, found that weight gain below the reference category of 21 pounds to 30 pounds significantly increased the risk of preterm delivery with PROM while weight gain above the reference category significantly reduced the risk of PROM. Similar trends were noted for full-term PROM. However, they were statistically significant only for gestational weight gain of 31 to 40 pounds when compared with women who gained 21 to 30 pounds (OR, 0.56; 95% CI, 0.33-0.94). Many potential confounders and effect modifiers were included in the analyses, including diet quality, BMI, age, race, parity, gestational iron supplementation, various medical conditions such as chlamydia that are considered risks for PROM, and smoking. The authors did not say if they adjusted for gestational age as a continuous variable. All variables, including pregravid

weight and total weight gain, were assessed through a questionnaire administered to most of the subjects within 72 hours of giving birth.

Results for rate of weight gain In the Danish cohort study, women with a weekly weight gain of less than 275 grams per week had an adjusted hazards ratio for PROM of 1.5 (95% CI, 1.2-1.7) compared with women gaining between 276 grams and 675 grams weekly. When compared with women with BMIs of 18.5 to 24.9, those with either low (< 18.5) or high (> 30) BMIs had significantly higher rates of preterm delivery with PROM. The authors adjusted for prepregnancy BMI, weight gain, parity, mother’s age, socio-occupational status, and lifestyle exposures in early pregnancy including smoking and alcohol exposure.⁶⁵

Study characteristics One poor study (Evidence Table 7) examined the relationship between gestational weight gain and preterm labor.⁶⁶ Preterm labor was not defined. This study, set in the United States, examined data from 11,505 women at the Boston Hospital for Women. The study defined gestational weight gain as pounds gained per week (≤ 0.4, 0.41 to 0.65, 0.66 to 0.9, and > 0.9).

Overview of results One poor study suggested that weight gain below 0.65 to 0.9 pounds per week significantly increased the risk of preterm labor.⁶⁶

Results After controlling for an extensive list of confounders and effect modifiers (race, height, prepregnancy weight, infant sex, maternal age, education, health insurance, marital status, planned pregnancy, parity, previous induced or spontaneous abortion, previous stillbirth, uterine exposure to diethylstilbestrol, incompetent cervix, uterine anomaly, maternal morbidity, substance abuse, caffeine use, and prenatal care), the study found that weight below the reference range of 0.66 to 0.9 pounds per week significantly increased the risk of premature labor (AOR for 0.41-0.65 pounds per week: 1.7, 95% CI, 1.3-2.1; AOR for ≥ 0.4 pounds per week: 3.0; 95% CI, 2.2-4.2). Weight gain above 0.9 pounds per week did not have a significant effect on premature labor.

Study characteristics One study⁵⁸ used data from 245,526 pregnancies identified through the Swedish Medical Birth Registry (Evidence Table 8).

Overview of results One fair study found no evidence of association between gestational weight gain and postterm gestation.⁵⁸

Results The author examined the effects of low (< 8 kg) and high weight gain (> 16 kg), compared with the effect of average weight gain (8-16 kg), on deliveries at > 41 weeks of gestation across strata of maternal pregravid BMI strata. After adjusting estimates for maternal age, parity, smoking in early pregnancy, and year of birth, no significant associations emerged between gestational weight gain and postterm gestational age. The study suggests that low or high gestational weight gain has no effect on postterm gestation.

Study characteristics Five studies examined the relationship between gestational weight gain and labor induction (Table 6, Evidence Table 9) Of these, three were set in the United States,^25,51,67 one in Denmark,⁵⁹ and one in Finland.⁶⁸ Of these five studies, three were of poor quality.^51,59,68 Three examined induction of labor^59,67,68 and two examined failed induction of labor (defined as a birth that required a cesarean delivery despite induction of labor).^25,51 One of five studies was limited to obese, glucose-tolerant women,⁶⁷ and one to women of normal weight;²⁵ the other studies included women with a range of pregravid BMI. Each of the five studies defined gestational weight gain differently. Three used categories of gestational weight gain, with different cutpoints.^25,59,67 One stratified its sample by weight gain categories, comparing women with normal prepregnancy weight and weight gain during pregnancy with those with abnormal weight gain during pregnancy, defined as ≥ 20 kg or ≤ 5 kg during pregnancy; the study did not specify the prepregnancy weight status of women in these “abnormal” weight gain categories.⁶⁸ Another study characterized weight gain as change in BMI class between prepregnancy weight and weight at delivery.⁵¹ The study defined BMI categories as follows: normal, BMI 20 to 24.9; overweight, BMI 25 to 29.9; obese I, BMI 30 to 34.9; obese II, BMI 35 to 39.9; morbid obesity, BMI ≥ 40.51.

Overview of results Two fair^25,67 and three poor^51,59,68 studies examined the association of increased gestational weight gain and labor induction^59,67,68 or failure of labor induction,^25,51 and found a risk of labor induction or failure of induction with increased gestational weight gain.

Results The three studies that looked at induction of labor found a statistically significant increase in the risk of labor induction with increases in gestational weight gain.^59,67,68 The magnitude of the effect across all three studies cannot be summarized because of differences in the definition of weight gain and in the nature of confounders controlled for in the analysis. Both studies examining failed induction of labor found a significant as-

sociation between gestational weight gain and increase in the risk of failed induction compared with all other delivery routes.^25,51

Study characteristics Three cohort studies, set in Finland and the United States, examined the association between gestational weight gain and labor (Table 7, Evidence Table 10).^68-70 Two studies focused on length of labor,^68,69 one on labor abnormalities.⁷⁰ The definition of gestational weight gain differed across studies. One study examined an overall increase in weight of > 25 percent or ≤ 25 percent for women with normal pregravid weight (90-120 percent of normal weight for height based on Metropolitan Life Insurance Company Table for 1983).⁶⁹ Another reported on categories of gestational weight gain (< 16 pounds, 16-25 pounds, 26-35 pounds, and > 35 pounds) for pregravid BMI categories defined by the IOM.⁷⁰ The third study, of poor quality, stratified its sample by weight gain categories, comparing women with normal prepregnancy weight and weight gain during pregnancy with those with abnormal weight gain (≥ 20 kg, or ≤ 5 kg) during pregnancy; the study did not specify the prepregnancy weight status of women in these “abnormal” weight gain categories.⁶⁸

Overview of results Two of three studies (2 fair,^69,70 1 poor⁶⁸) suggested that higher weight gain among normal weight women of normal weight was associated with longer labor.^68,69

Results The two studies that examined length of labor demonstrated significantly longer second stage of labor for women with high weight gain, based on samples of 35,768 and 10,469 respectively. Neither study controlled for confounders or effect modifiers.

The study that reported on labor abnormalities found higher odds of labor abnormalities for women gaining > 35 pounds compared with women gaining < 16 pounds. These odds lost statistical significance when adjusted for confounders. In a trend analysis, the study found a higher risk of labor abnormalities with increased weight gain, suggesting that a difference of 10 pounds corresponds to an OR of 2 (P < 0.0001) after adjusting for BMI, patient care (private vs. nonprivate), parity, infant sex, hypertension, and macrosomia.⁷⁰

Study characteristics Twenty-one cohort studies reported on the relationship between gestational weight gain and mode of delivery (Table 8, Evidence Table 11).^{4,25,49,51,52,54,58,59,61,67-78} Thirteen studies were set in the United States,^{4,25,51,54,67,69-71,73-77} three in Canada,^49,53,72,78 two in Ja-pan,^52,61 one in Sweden,⁵⁸ one in Denmark,⁵⁹ and one in Finland.⁶⁸

All 21 studies examined cesarean delivery as an outcome. Five examined instrumental delivery in addition to cesarean delivery.^{25,51,58,68,69} Eight studies reported on cesarean delivery without providing further definition.^{4,25,49,54,58,59,74,76} The studies that offered some detail varied in their definition; these studies defined cesarean delivery as failure to progress,⁵¹ unscheduled cesarean,^67,70 cesarean including elective and emergency,⁵² elective cesarean and emergency cesarean,^61,68 cephalopelvic disproportion/failure to progress, fetal distress, breech, and other indications,⁷³ cesarean delivery for cephalic presentation,⁷⁷ and cesarean delivery for singleton cephalic presentation separately analyzed for primary and repeat cesareans, with and without labor.⁷⁸ A key consideration in assessing the risk of cesarean delivery is the route of previous delivery; with the declining prevalence of vaginal birth after cesarean (VBAC), a history of prior cesarean delivery is likely to result in cesareans for all subsequent pregnancies. Studies that fail to account for prior route of delivery cannot therefore control for its confounding effect. Eleven studies did not take into account prior route of delivery.^{4,25,49,52,54,58,59,61,67,68,70}

Definitions of gestational weight gain also varied greatly. Some studies used categorical definitions designed to identify high weight gain alone,^67,71 weight gain across a spectrum of gain,^{4,25,49,52,54,58,59,70,72,74,77} continuous weight gain,^73,76 rate of weight gain,^61,78 and weight gain in relation to pregravid weight.^51,68,69,75

Overview of results Across the 14 fair^{4,25,52,58,67,69-73,75-78} and 7 poor^{49,51,54,59,61,68,74} studies that examined gestational weight gain as a predictor of route of delivery, only four (2 poor) failed to show an effect of gestational weight gain on route of delivery.^49,52,54,67 The remainder demonstrated higher risks of cesarean delivery associated with gestational weight gain, with some evidence suggesting more pronounced risks associated with high pregravid BMI status. Notably, only 10 studies controlled for route of previous delivery. Of these, five controlled for co-morbidities that could have been significant confounders for route of delivery.^{71,72,75,76,78} One study explicitly examined the interactions between weight gain and pregravid weight; it did not find any significant effect.⁷⁷

Results across BMI categories for categorical measures of weight gain. Fifteen studies considered weight gain across a range of pregravid weight categories. Of these, two fair studies defined gestational weight gain as a categorical variable (≤ 45 pounds vs. > 45 pounds,⁶⁷ and < 41 vs. ≥ 41 pounds⁷¹). One of these two studies, limited to primary cesarean, found a significant association between weight gain and cesarean delivery (AOR, 1.38; 95% CI, 1.34-1.41).⁷¹ This study found pregravid BMI, diabetes, and hypertension to also be strong predictors of cesarean delivery. The other,

which did not control for route of previous delivery, did not find any association between gestational weight gain and route of delivery.⁶⁷

Six studies defined gestational weight gain in categories that allowed for the identification of both low and high weight gain, across a spectrum of pregravid weight categories;^{52,58,70,72,74} of these, one was rated poor quality⁷⁴ and the remainder fair. One study showed no difference in cesar-

ean delivery by weight gain category.⁵² All others showed some patterns of association with higher levels of weight gain, although the magnitude of the effect varied.^58,70,72,74 Three studies found similar thresholds for the rise in risk of cesarean delivery, namely, weight gains in excess of 15 kg⁷² or greater than 35 pounds.^70,77 One study looked at both relatively low weight gain (< 8 kg) and relatively high weight gain (> 16 kg) in comparison with

weight gain of 8 to 16 kg.⁵⁸ The study found no statistically significant risk of cesarean delivery for low or normal BMI categories but significantly higher risk with higher weight gain for overweight, obese, and morbidly obese women.⁵⁸ One study examined the effects of pregravid weight, gestational weight gain, and the interaction between the two as predictors of cesarean delivery for primiparous and multiparous women (defined in two different ways). The study found that pregravid overweight or obese status as well as weight gain over 35 pounds are associated with the risk of cesarean delivery for primiparous women, but no significant effect of the interaction between weight gain and pregravid weight. The study did not find consistently significant effects of these variables on cesarean delivery for multiparous women; the previous route of delivery, a likely confounder, was not controlled in these analyses.

Results across BMI categories for rate of weight gain. Two studies, one rated fair⁷⁸ and the other poor,⁶¹ examined the rate of weight gain across a range of pregravid weight categories. The fair study separately examined the risks of primary and repeat cesarean, with and without labor in models that accounted for gestational diabetes, pregnancy-induced hypertension, macrosomia, socioeconomic factors, parity, or maternal age. The study found that a high rate of weight gain (> 0.5 kg/week) significantly increased the risk of a labored primary cesarean, while a low rate of weight gain (≤ 0.17 kg/week) significantly reduced the risk, compared with an average rate of weight gain (0.18-0.50 kg/week). High rate of weight gain significantly increased the risk of unlabored repeat cesareans. The rate of weight gain during pregnancy did not predict the risk of primary unlabored cesarean or repeat labored cesarean. In contrast, pregravid overweight and obese status was a significant risk factor for all types of cesarean delivery. The poor study examined associations between cesarean delivery and rates of weekly weight gain (seven categories), categorized differently across different BMI groups (three groups) and parity (two categories), resulting in 42 comparisons.⁶¹ As with the fair study, a subset of results were significant, suggesting that for nulliparous women with low or medium BMI, high rates of weight gain increased the risks of cesarean delivery. Specifically, the study found:

• among nulliparous, low-BMI women, a higher risk of elective cesarean delivery for women with weight gain ≥ 0.4 kg per week (AOR: 2.30 [1.06-4.98]) than for women gaining between 0.25 and 0.3 kg per week.

• among nulliparous, medium-BMI women, a higher risk of elective cesarean delivery

  • for women with weight gain ≥ 0.4 kg per week (AOR: 1.61

[1.21-2.14]) than for women gaining 0.25 to 0.3 kg per week and

• for women with weight gain of 0.35 to 0.4 kg per week (AOR: 1.68 [1.22-2.30]) than for women gaining 0.25-0.3 kg per week.

The study examined risk of emergency (rather than elective) cesarean for high BMI nulliparous women and failed to find an association with gestational weight gain rates.

In examining outcomes for parous women, with a single exception—a higher risk of cesarean delivery for women with weight gain 0.25-0.3 kg/wk (AOR, 1.49 [1.09-2.04]) than for women gaining 0.20 to 0.25 kg/week—the poor study did not find statistically significant effects for rate of weight gain on cesarean delivery for parous, medium-BMI women. No data were presented on cesarean delivery (emergency or elective) for low or high BMI groups for parous women.

Results across BMI categories for continuous measures of weight gain Of the 15 studies that considered a range of pregravid weight categories, two fair studies modeled gestational weight gain as a continuous variable.^73,76 Both found significantly higher risks of cesarean delivery with increasing weight. One study identified the progression of AOR of cesarean delivery weight gain for every 5 pounds of gestational weight gain to be 1.094 (95% CI, 1.074-1.115).⁷³ The second study calculated the attributable risk for cesarean delivery of gaining more than 16 kg to be 6.9 percent.⁷⁶ Both studies account for route of previous delivery.

Results across BMI categories for other measures of weight gain Of these same 15 studies, three (1 fair,⁷⁵ and 2 poor^51,53,68) defined gestational weight gain as a function of pregravid weight.^51,68,75 Two of three studies controlled for previous route of delivery by limiting their sample to primary cesareans. The fair study used underweight women who gained less than the median for proportional weight gain (total weight gain/prepregnancy weight) as the referent.⁷⁵ This study found higher risks of cesarean delivery for all other categories, although risks were statistically significant only for women in the high and obese BMI category in all weight gain categories and women in the average BMI category who gained less than the median proportional weight gain. One poor-quality study characterized weight gain as change in BMI class between prepregnancy weight and at delivery. BMI categories were defined as follows: normal, BMI 20 to 24.9; overweight, BMI 25 to 29.9; obese I, BMI 30 to 34.9; obese II, BMI 35 to 39.9; morbid obesity, BMI ≥ 40.51 This study found no statistically significant association between weight gain and cesarean delivery among normal-BMI women but did find a positive association for high-BMI women. The extent to which

these results corroborate findings from the fair study is hard to determine given the differences in the reference category, but both studies imply that increased risks of cesarean are pronounced among overweight and obese women. A third study, also of poor quality, examined differences in route of delivery between women with normal prepregnancy weight and weight gain during pregnancy with those with abnormal weight gain (≥ 20 kg or ≤ 5 kg) during pregnancy; the study did not specify the prepregnancy weight status of women in these “abnormal” weight gain categories.⁶⁸ Unlike the other two studies in this category, the rates for cesarean delivery were not statistically significantly different across groups. The study did find a statistically significant higher rate of normal vaginal delivery for low weight gain women compared with the reference category of normal prepregnancy weight and weight gain. Notably, this study did not control for route of previous delivery.

Results within BMI categories for other measures of weight gain. Two studies were limited to women of normal BMI.^25,69 Both suggested an increase in the risk of cesarean delivery with increasing weight gain, defined in one study as 25 percent gain over prepregnancy weight,⁶⁹ and in the other as a weight gain > 35 pounds as compared with a weight gain of 30 to 35 pounds. Weight gain of < 30 pounds was associated with a lower risk of cesarean delivery, suggesting a linear increase in the risk of cesarean delivery with weight gain for women of normal weight. One of the two studies controlled for previous cesarean delivery by limiting its sample to primigravidas.⁶⁹

Four studies limited their analysis to obese women or morbidly obese women.^4,49,54,59 Of these, two studies (both rated poor quality) suggested no difference in cesarean delivery outcomes by gestational weight gain.^49,54 Neither accounted for route of previous delivery.

The other two studies suggested that the risk of cesarean delivery increased with higher levels of weight gain for obese and morbidly obese women.^4,59 One poor study suggested that risk increases with higher levels of weight gain.⁵⁹ Compared with the risk of cesarean delivery for women gaining < 5 kg, the results were as follows: AOR of cesarean delivery for women gaining 5 to 9.9 kg, 2.4 (95% CI, 1.1-5.3); AOR for women gaining 10 to 14.9 kg, 3.0 (95% CI, 1.4-6.4); and AOR for women gaining ≥ 15 kg, 3.6 (95% CI, 1.6-7.8).⁵⁹ The other study suggested that women who had lower weight gain than women who gained 15 to 25 pounds had lower risks of cesarean delivery, but the magnitude of the association varied by obesity classification.⁴ Overall, across a range of outcomes the study suggested that minimal risk may correspond to a weight gain of 10 to 25 pounds for class I obese women (BMI 30-34.9), a weight gain of 0 to 9 pounds for class II obese women (BMI 35-39.9), and a weight loss of 0 to 9 pounds for class III obese women (BMI > 40). Neither of these studies controlled for route of previous delivery.

Results for instrumental delivery Five studies examined instrumental delivery in addition to cesarean delivery.^{25,51,58,68,69} Two found no association.^25,68 Of the remaining studies, one found a higher risk of instrumental delivery with increased weight gain only for normal BMI and overweight women,⁵⁸ and a second found this only for overweight women.⁵¹ A third study, limited to women of normal weight, examined differences in the rate of vacuum extraction and forceps delivery by amount of weight gain; it found a higher rate of vacuum extraction with excessive weight gain but no difference in rate of forceps delivery.⁶⁹

Results controlling for confounding Studies varied in their adjustment for confounding factors. Seven studies controlled for route of previous delivery by limiting their sample to primary cesarean^51,71,72,75 or primigravidas.^69,73,74 Three studies included multigravidas but accounted for previous cesarean delivery in the analysis.^76-78 The remaining 11 studies did not control for route of previous delivery.^{4,25,49,52,54,58,59,61,67,68,70}

Of the 10 studies that controlled for route of previous delivery, five studies examined underlying health risks (e.g., preeclampsia, pregnancy-induced hypertension) as predictors of cesarean delivery; all five found these health factors to be significantly associated with risks of cesarean delivery.^{71,72,75,76,78}

Study characteristics One U.S. cohort study (rated poor quality) examined the effect of weight gain on the success of vaginal birth after cesarean (VBAC) (Evidence Table 12).⁷⁹

Overview of results A single poor study found that gestational weight gain of 40 pounds or more increased the risk of VBAC failure.

Results Women who gained more than 40 pounds during pregnancy were less likely to have VBAC success than women who gained 40 pounds or less (OR, 0.65; 95% CI, 0.42-0.98). This study controlled for previous normal spontaneous vaginal delivery, previous VBAC, diabetes, induction, birthweight > 4,000 g, recurrent indication, one layer closure, pregnancy complications, and BMI, but it failed to account for age or parity. The study suggested that pregravid BMI was also a predictor of VBAC success, with lower pregravid BMI being predictive of success.

Study characteristics Two cohort studies examined vaginal lacerations (Evidence Table 13).^51,68 One U.S. study (rated poor quality) examined the incidence of third- or fourth-degree lacerations among women.⁵¹ Weight gain was characterized as change in BMI class between prepregnancy

weight and weight at delivery. BMI categories were defined as follows: normal, BMI 20 to 24.9; overweight, BMI 25 to 29.9; obese I, BMI 30 to 34.9; obese II, BMI 35 to 39.9; morbid obesity, BMI ≥ 40. The second study (described earlier, also rated poor quality) was set in Finland.⁶⁸ It examined the rate of vaginal repairs for women with normal prepregnancy weight and weight gain during pregnancy and for those with abnormal weight gain (≥ 20 kg, or ≤ 5 kg) during pregnancy.⁶⁸

Overview of results Two studies, both of poor quality, did not report consistent results on the effects of gestational weight gain on vaginal lacerations.

Results The U.S. study found no differences in the incidence of third-and fourth-degree lacerations among women who were overweight before pregnancy.⁵¹ It did find a statistically significant difference among normal weight women; the incidence of lacerations rose from 24 percent for women with no change in BMI category to 29.3 percent for women gaining enough to change weight status by one BMI category and to 31.7 percent for women who gained enough to change weight status by more than one BMI category. The Finnish study found no statistical differences between study and control mothers in the rate of repair of second- or third-degree lacerations.⁶⁸ Neither study controlled for any variable other than pregravid BMI.

Study characteristics Three studies, set in Ireland,⁸⁰ the United States,⁵¹ and Finland,⁶⁸ examined the effect of gestational weight gain on shoulder dystocia (Table 9, Evidence Table 14). The Irish study, a case-control investigation (rated poor) comparing cesarean delivery for shoulder dystocia with cephalic vaginal term deliveries, distinguished between two groups of gestational weight gain (< 12 kg and ≥ 12 kg).⁸⁰ The Finnish study (described earlier and rated poor quality), stratified its sample by weight gain categories, comparing women with normal prepregnancy weight and weight gain during pregnancy with those with abnormal weight gain (≥ 20 kg or ≤ 5 kg) during pregnancy.⁶⁸ The U.S. case-control study (also rated poor quality), stratified its sample between normal and overweight BMI categories and examined the effect of change in BMI class between prepregnancy weight and weight at delivery. The Irish study defined shoulder dystocia to include mild, moderate, and severe cases;⁸⁰ the other two studies did not define their outcome variable.^51,68

Overview of results Only one⁸⁰ of three poor studies found a positive association between gestational weight gain and shoulder dystocia.

Results The three studies found rates of shoulder dystocia ranging from 0.6 percent to 1.4 percent.^51,68,80 Two studies reported no statistically significant differences in rates of shoulder dystocia between weight gain groups.^51,68 The Irish case-control investigation found that higher gestational weight gain during pregnancy was a significant predictor of shoulder dystocia (OR, 2.0; 95% CI, 1.6-2.2; P = 0.015). The authors calculated positive predictive value percentages from the study group and applied them to the total hospital population of singleton vaginal deliveries without shoulder dystocia over the same time period. These results suggest a positive predictive value of 1 percent for shoulder dystocia when gestational weight gain is 12 kg or greater.

The Irish study accounted for a subset of confounders and effect modifiers other than pregravid BMI.⁸⁰ Multiparity and birth of a previous heavy baby were significant and independent determinants for shoulder dystocia, in addition to gestational weight gain. However, the investigators noted that each predictor individually accounted for less than 2 percent of the positive predictive value for shoulder dystocia, and all three put together accounted for less than 3 percent.

Study characteristics Two U.S. cohort studies examined the association between gestational weight gain and cephalopelvic disproportion (CPD) (Evidence Table 15).^25,74 One study, using Missouri birth certificate data, defined CPD as the condition when the size, presentation, or position of the fetal head to the maternal pelvis prevented cervical dilation or descent of the fetal head.²⁵ This study controlled for a range of demographic confounders but not for maternal health characteristics.²⁵ The other study (rated poor quality) defined CPD among primiparous women as little or no progress over a 2- to 4-hour period, with contractions documented to be adequate and cervix dilated to at least 3 cm or preferably 4 cm. However, if the delivering physician defined the indication as CPD, the decision was accepted without chart review, despite the definitions listed earlier.⁷⁴

Both studies defined weight gain in categories: < 30 pounds, 30 to 35 pounds, and > 35 pounds. The study using birth certificate data limited inclusion to normal weight women (pregravid BMI 19.8-26.0);²⁵ the other study examined the association between gestational weight gain and CPD across four pregravid BMI categories: < 20, 20 to 25, 25 to 30, and > 30.

Overview of results Both studies (1 fair²⁵ and 1 poor⁷⁴) showed that, for normal-weight women, the risk of CPD rose with higher gestational weight gain

Results The fair study reported an AOR of 1.58 (95% CI, 1.44-1.75) for women gaining > 35 pounds compared with women gaining 25

to 30 pounds, after adjusting for maternal age, maternal race or ethnicity, maternal education, Medicaid status, tobacco use, alcohol use, maternal height, prior pregnancy, adequacy of prenatal care, child’s sex, and child’s birth year.²⁵ The poor study showed similar results, with an unadjusted OR of CPD of 1.85 (95% CI, 1.63-2.06) for normal-weight women gaining > 35 pounds compared with women gaining < 30 pounds. This study also showed an increased risk of CPD for underweight women gaining > 35 pounds compared with women gaining < 30 pounds (unadjusted OR: 3.8; 95% CI, 3-4.6). The relationship between weight gain and CPD was not statistically significant at higher pregravid BMI levels.⁷⁴

Study characteristics Two retrospective cohort studies, one from Iceland⁵³ and the other from the United States,⁸¹ evaluated the impact of gestational weight gain on complications of labor and delivery (Evidence Table 16).

Overview of results Two studies, of fair⁵³ and poor⁸¹ quality respectively found conflicting evidence on the risks of complications. One failed to find statistically significant results;⁵³ the other reported that gestational weight gain of more than 40 pounds increased the risk for the previously listed complications by 40 percent.⁸¹

Results The fair study from Iceland analyzed the quartiles of total weight gain in women with normal pregravid BMIs (19.5-25.5) to determine the impact of weight gain on labor and delivery processes.⁵³ After adjusting for age, height, parity, gestational length, and birthweight, they found that weight gain of 11.5 to 16.0 kg was associated with the highest likelihood of a normal vaginal delivery, defined to include no shoulder dystocia and no asphyxia, and the least likelihood of operative procedures including cesarean delivery and forceps- or vacuum-assisted deliveries. The findings of this study, however, were not statistically significant.

The poor U.S. study enrolled 493 women at 37 or more weeks of gestational age to determine the relationship between various lifestyle choices and complications in term pregnancy.⁸¹ Complications included dystocia, postpartum hemorrhage, retained placenta, fetal and neonatal distress, and pregnancy-induced hypertension. All complications were grouped together for the analysis. Smoking had a protective effect against complications, but entering pregnancy with excess weight for height and gaining more than 40 pounds during gestation both predicted complications. A gestational weight gain of more than 40 pounds increased the risk for the previously listed complications by 40 percent.

Study characteristics Twelve studies (Table 10, Evidence Table 17) examined the relationship between weight gain and birth outcomes.^{23,59,65,71,82-89} These include eight cohort studies,^{59,65,82-86,89} two case-control studies,^87,88 and two cross-sectional studies.^23,71 The majority of the studies defined preterm birth as delivery occurring prior to 37 weeks of gestation; the one exception defined it as delivery between 24 and 35 weeks of gestation.⁸⁷ Each study defined weight gain differently. Two studies examined associations of weight gain with early and late preterm birth,^23,65 and two studies examined associations across subtypes of preterm delivery.^65,84

Overview of results Taken collectively, the results of these two good,^84,88 seven fair,^{23,65,71,82,85,86,89} and three poor^53,59,83,87 studies suggest an association between preterm birth and both low and high rates of weight gain and with low total weight gain, with one study reporting a 16 percent decrease in preterm birth associated with a 1 kg increase in maternal weight. The cut points for low and high weight gains and the severity of the risks of preterm birth associated with them differ by pregravid BMI. In general, low rates of weight gain were ≤ 0.37 kg per week and high rates of gain were > 0.52 kg per week throughout gestation, with the greatest risks found among underweight women. However, as pregravid BMI increases, the risk of preterm birth decreases for women gaining in the lower range of the low rate of weight gain and increases for women gaining in the lower range of the high rate of weight gain, such that the range of adequate rates of weight gain is shifted down for heavier women compared to their lighter counterparts. Some evidence also suggests that low rate of weight gain is associated with greater risks of early preterm birth as well as preterm birth due to premature rupture of the amniotic membranes.

Detailed results from categorical measures of total rate of weight gain. Four studies used categorical definitions of rate of weight gain averaged for the entire length of gestation;^85,86,88,89 one study was rated good⁸⁸ and the others rated fair.^85,86,89 In the good study,⁸⁸ a rate of weight gain of < 0.27 kg per week was not associated with preterm birth (OR, 1.56; 95% CI, 0.94-2.58). Among the fair studies, all three studies found evidence of an association between low rate of weight gain and preterm birth, and two studies found evidence of an association between high rate of weight gain and preterm birth.^86,89

One study used a retrospective, U.S.-hospital-based cohort of deliveries from 1976 to 2001 to examine the association of preterm birth and gestational weight gain by maternal race or ethnicity.⁸⁵ Weight gain was categorized into three groups based on rate of weight gain: < 0.27 kg per week,

0.27-0.52 kg per week, and > 0.52 kg per week. Within the entire cohort and across four racial or ethnic groups (white, black, Latina, and Asian), the highest percentages of preterm birth occurred among women gaining < 0.27 kg per week. The adjusted odds of spontaneous preterm birth were 2.5 times higher in women with rates of weight gain < 0.27 kg per week than in women gaining 0.27 to 0.52 kg per week. The adjusted odds ratios for this association were statistically significant across the different racial or ethnic groups, ranging from 2.1 (95% CI, 1.4-3.1) for white women to 3.6 (95% CI, 2.2-6.0) for black women. No association between spontaneous preterm birth and rate of weight gain > 0.52 kg per week (relative to a weight gain of 0.27 to 0.52 kg per week) was seen either within the entire cohort or across the racial or ethnic groups.

Another study, conducted in a population of young, primarily black, disadvantaged women, found statistically significant higher odds of preterm delivery among women gaining < 0.24 kg per week and > 0.74 kg per week than among women gaining 0.58 to 0.74 kg per week.⁸⁹

The final study used data collected from women participating in U.S. federally funded prenatal public health programs via the Pregnancy Nutrition Surveillance System (PNSS).⁸⁶ Gestational weight gain was defined as rates of weight gain and net weight gain (kg/week) and categorized by the percentile distributions based on the total sample. Women with rates of weight gain between 0.35 and 0.46 kg per wk (the 50th through the 74th percentiles) were used as the reference for risk difference calculations. In general, the risk of preterm birth was highest among women with the small-

est and greatest rates of weight gain, < 0.10 kg per week and ≥ 0.65 kg per week, respectively. The lowest risks of preterm delivery occurred among women gaining between 0.26 and 0.46 kg per week (the 25th through the 74th percentiles). Preterm risk differences did vary by maternal pregravid BMI status. An increased risk of preterm birth was associated with rates of weight gain for the following pregravid BMI categories:

• pregravid BMI < 19.8: < 0.26 kg per week;

• pregravid BMI of 19.8 to 26.0: < 0.26 kg per week and > 0.65 kg per week;

• pregravid BMI of 26.1 to 29.0: < 0.10 kg per week and > 0.65 kg per week; and

• pregravid BMI > 29.0: ≥ 0.57 kg per week.

The results were similar when rates of weight gain per week excluded the first 14 weeks of gestation.

Results from categorical measures of trimester rate of weight gain Four studies used categorical definitions of rate of gestational weight gain measured during specific trimesters of pregnancy.^23,65,84,87 All of the studies found evidence for an association between preterm birth and low rate of weight gain and two studies found evidence for an association between preterm birth and high rate of weight gain.

One study of good quality used a cohort of mainly Hispanic women recruited from public health clinics to examine the association between preterm birth and rate of weight gain during the third trimester.⁸⁴ Women with preterm deliveries had significantly lower rates of third trimester weight gain than women with term deliveries, 0.50 (standard error of mean [SEM]: 0.02) kg per week versus 0.53 (SEM: 0.004) kg per week, respectively (P < 0.05). The odds of preterm birth were 1.91 (95% CI, 1.40-2.61) times greater among women with inadequate third trimester weight gains (defined as a rate of weight gain less than the 25th percentile of gain in each pregravid weight status: 0.34 kg/week, underweight; 0.35 kg/week, normal weight; 0.30 kg/week, overweight and obese) than among women with adequate rates of weight gain. When data were stratified by the type of preterm delivery, women with inadequate weight gains were 1.75 (95% CI, 1.15-2.64) times more likely to have preterm delivery resulting from preterm labor and 2.70 (95% CI, 1.32-5.42) times more likely to have preterm delivery resulting from preterm premature rupture of the amniotic membranes (PPROM) than women with adequate rates of weight gain.

One study, rated fair quality, used data from the Danish National Birth Cohort to assess the impact of gestational weight gain on early (22-

33 weeks), late (34-36 weeks), and all (22-36 weeks) preterm births with PPROM, without PPROM, and with medical inducement.⁶⁵ Gestational weight gain was categorized as low (< 275 g/week), medium (275-675 g/week), and high (> 675 g/week) based on two self-reported measurements recorded at least 6 weeks apart between 12 and 37 weeks of gestation. Women with medium rates of weight gain were used as the reference. Overall, low rates of weight gain were significantly associated with an increased risk of early spontaneous preterm birth with and without PPROM and with all spontaneous preterm births with PPROM, adjusted odds ratios ranged from 1.5 to 2.1. High rates of weight gain were significantly associated with an increased risk of early spontaneous preterm births without PPROM (AOR, 1.9; 95% CI, 1.3-2.6) and early, late, and all medically induced early preterm births. However, when women with obesity-related diseases and abruptio placenta were excluded, the associations for medically induced preterm births were no longer significant.

Another fair quality study used information collected for the Pregnancy Risk Assessment Monitoring System (PRAMS) to examine the effect of rate of weight gain during the second and third trimesters on preterm birth.²³ These investigators stratified women by prepregnancy BMI status and examined the risk of preterm birth in two categories: moderate length of gestation (32-36 weeks) and very short length of gestation (20 to 31 weeks). Second and third trimester rate of weight gain was categorized, in kg per week, as follows: < 0.12, 0.12-0.22, 0.23-0.68, 0.69-0.79, and > 0.79; the investigators also used five pregravid BMI groups: underweight (< 19.8), normal weight (19.8-26.0), overweight (26.1-28.9), obese (29.0-34.9), and very obese (≥ 35.0). Women of normal weight with rates of weight gain of 0.23 to 0.68 kg per week were used as the reference for analyses. After adjusting for covariates and excluding women with diabetes, hypertension, or small-for-gestational-age (SGA) infants, significant associations (AOR range, 1.3-3.1) were reported between moderate preterm birth and rates of weight gain as follows: < 0.69 and > 0.79 kg per week among underweight women; < 0.23 and > 0.79 kg per week among normal weight women; and 0.69 to 0.79 kg per week among obese and very obese women. Significant associations (AOR range, 1.5-9.8) were reported between very preterm birth and rates of weight gain as follows: all weight gain categories among underweight women; < 0.23 and > 0.79 kg per week among normal weight women; < 0.12 and > 0.79 kg per week among overweight and obese women; and < 0.12 and > 0.68 kg per week among very obese women. In general, the greatest odds were found among underweight women and in the extreme weight gain categories.

Results from a poor study⁸⁷ were consistent with those of the other studies and revealed an overall increased odds of preterm birth (between 24

and 35 weeks’ gestation) with gestational weight gain ≤ 0.37 kg per week in the second and third trimesters; however, the odds were greater among women with pregravid BMI ≤ 19.5 compared to those with BMI > 19.5.

Results from categorical measures of total weight gain Two studies,^59,71 one rated fair and the other poor, used categories of total weight gain. In the fair study, data from the New York City birth file from 1999 through 2001 was used to examine the odds of preterm birth associated with different levels of gestational weight gain.⁷¹ After adjusting for covariates, the investigators determined that the odds of preterm birth were significantly decreased (OR, 0.54; 95% CI, 0.52-0.57) among women who gained at least 41 pounds compared with women who gained less than 41 pounds. Results from the poor study,⁵⁹ which used a population of obese women, showed the highest proportion of preterm birth among those with the lowest gestational weight gain (< 5.0 kg).

Results from continuous measures of weight gain The remaining two studies, one rated fair and the other poor, used gestational weight gain as a continuous measure.^82,83 Both studies reported a significant increase in length of gestation for a 1 kg increase in total gestational weight gain.

In the fair study,⁸² simple regression techniques were used to develop a variable for pattern of weight gain that reflected the variation between a woman’s pattern of weight gain and a linear pattern of weight gain.⁸² Deviations in the pattern of weight gain, such as pronounced speeding up or slowing down of weight gain later in gestation, from an average pattern of weight gain were associated with decreased gestational age and increased risk of spontaneous preterm birth. A 1-kg increase in total gestational weight gain was associated with 0.51 day’s increase in gestational age (P < 0.001). The odds of spontaneous preterm birth were decreased by 16 percent for each 1-kg increase in total gestational weight gain (OR, 0.84; 95% CI, 0.82-0.87; P < 0.001).

Study characteristics Twenty-five studies examined the association between gestational weight gain and infant birthweight (Evidence Table 18).^{48,54,55,59,68,70,75,83,90-106} These studies consisted of various groups of women, in many different countries. Nine studies were completed outside the United States, in Canada,¹⁰⁵ France,^83,92 Italy,^91,100 Denmark,⁵⁹ Norway and Sweden,⁹⁹ Finland,⁶⁸ and Austria.⁹³

One study observed the association for adolescent mothers.⁹⁵ The association was also evaluated for mothers with gestational diabetes mellitus (GDM),¹⁰⁰ mothers who had a positive diabetic screen but normal glucose tolerance levels,⁹¹ and obese glucose-tolerant women.⁵⁹ Seven-

teen studies adjusted their analyses for multiple confounders, including maternal age, BMI, smoking, glucose levels, race, marital status, and parity.^{48,55,59,70,75,90-93,97-103,105}

Overview of results The results for four good,^{48,98,103,10612} fair,^{55,65,70,75,92,93,97,99-102,104,105} and nine poor^{54,59,68,83,90,91,94-96} studies consistently demonstrate an association between higher gestational weight gain and birthweight.