Preterm Birth Causes, Consequences, and Prevention (2007) / Chapter Skim
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SECTION III Diagnosis and Treatment of Preterm Labor: 9 Diagnosis and Treatment of Conditions Leading to Spontaneous Preterm Birth
SECTION III Diagnosis and Treatment of Preterm Labor: 9 Diagnosis and Treatment of Conditions Leading to Spontaneous Preterm Birth
Pages 259-307
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From page 261... ...
Preterm birth has historically not been emphasized in prenatal care, in the belief that the majority of preterm births are due to social rather than medical or obstetric causes or are the appropriate result of pathological processes that would benefit the mother or the infant, or both. Because preterm labor or premature rupture of membranes may occur in response to conditions that threaten fetal or maternal well-being, whether preterm birth is appropriately preventable is a topic that regularly influences clinical decision making.
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From page 262... ...
Efforts to prevent preterm birth must therefore be applied and evaluated primarily for their effects on perinatal mortality and morbidity. The care of infants born preterm and their mothers may be described as primary (prevention and reduction of risk in the population)
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From page 263... ...
or are the appropriate result of pathological processes that would benefit the mother or the infant, or both. More recently, the failure of repeated efforts to prevent preterm birth (see
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From page 264... ...
has lent support to the historical view. Because preterm labor or preterm premature rupture of membranes may occur in response to conditions that threaten fetal or maternal well-being, whether preterm birth is appropriately preventable is a topic that regularly influences clinical decision making.
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From page 265... ...
. The risk of recurrent preterm birth rises with the number of prior preterm births, with maternal African American ethnicity, and as the gestational age of the prior preterm birth decreases (Adams et al., 2000; Mercer et al., 1999)
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From page 266... ...
. As discussed in Chapter 5, the increased number of pregnancies conceived after the use of assisted reproductive technologies is associated with a rise in preterm birth not only because of multiple gestations but also because the singleton gestations that
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From page 267... ...
. Con TABLE 9-3 Prediction of Spontaneous Preterm Birth before 35 Weeks of Gestation (22 to 24 and 27 to 28 Weeks of Gestation)
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From page 268... ...
confirm the poor performance of contraction frequency as a test for acute preterm labor as well. Cervical Examination Manual examination Cervical dilatation, effacement, consistency, position, and station of the presenting part as determined by manual examination have been related to an increased risk of preterm birth (Copper et al., 1990; Iams et al., 1996; Mercer et al., 1996; Newman et al., 1997)
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From page 269... ...
, but a recent analysis of the relationship between gestational age at the time of detection of BV and pregnancy outcome in 12,937 women found "the odds ratio of preterm birth among BV-positive versus -negative women raged from 1.1 to 1.6 and did not vary significantly according to the gestational age at which BV was screened" (Klebanoff et al., 2005, p 470)
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From page 270... ...
Ureaplasma urealyticum 254 Amniotic fluid <17 <37 10 88 9 9 Relaxin 176 S/P <24 <34 6.8 27 4 64 Cervical length Meta-analysis Cervix <24 <34 6.3 29 Alkaline phosphatase 1,868 S/P <20 <37 4.6 14 3 69 CRH 860 S/P <30 <37 3.0 39 13 40 G-CSF 388 S/P 24 <32 3.3 49 15 16 Interleukin-6 250 V+C 24 <32 3.3 20 6 15 Interleukin-6 580 Amniotic fluid <20 <34 2.8 14 5 14 Fetal fibronectin Meta-analysis V+C >20 <37 2.9 22 254 S/P 24 <35 2.6 35 13 58 α-Fetoprotein Chlamydia 380 U 24 <37 2.5 16 6 10 Ferritin 100 S/P 34 <37 2.2 75 33 70 C-reactive protein 484 S/P <21 <37 1.8 26 15 75 Bacterial vaginosis Meta-analysis V+C <24 <37 1.6 8 Ferritin 364 V+C <25 <37 1.4 35 25 71 NOTE: LR+ = likelihood ratio; SENS = sensitivity; FP = false-positive rate; CRH = corticotropin-releasing hormone; G-CSF = granulocyte colonystimulating factor; U = uterine; V = vaginal secretions; C = cervical secretions; S/P = serum or plasma; GA = gestational age. aCitations in the paper by Vogel et al.
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From page 271... ...
by combining selected markers such as the woman's obstetric history and cervical length; for example, a sonographic cervical length less than 25 mm predicted recurrent preterm birth in 100 percent of African American women with a prior preterm birth (Yost et al., 2004)
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From page 272... ...
Importantly, the overlap between the biomarkers was small, supporting the concept that there are several heterogeneous pathways to spontaneous preterm birth. Use of the markers in concert improved the predictive ability.
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From page 273... ...
, successful removal of a risk factor has not produced a decrease in preterm birth rates. In fact, the overall rate of preterm birth has continued to increase.
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From page 274... ...
suppository and reduction 2003; Meis et al., intramuscular 17α- in preterm 2003; see also meta hydroxyprogesterone birth rates analyses by Dodd et caproate al., 2005; Sanchez Ramos et al., 1999 Prior preterm birth Nurse contact and/or No benefit CHUMS, 1995; and increased contraction monitor meta-analyses Dyson et al., 1998 contractions (singletons) Positive vaginal Antibiotics during No benefit; mixed Brocklehurst et al., swab cultures for pregnancy if also positive 2000; Gibbs et al., various organisms cultures VIP 1992; Carey and Klebanoff, 2003; Riggs and Klebanoff, 2004; Klebanoff et al., 2005
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From page 275... ...
mostly negative Berghella et al., 2005 Short cervix in Cerclage (usually with Mixed results Berghella et al., 2005 women with prior antibiotics at surgery) preterm birth Prior preterm birth Antibiotics before No benefit Andrews et al., 2006 next pregnancy Preterm labor in Nurse contact or No benefit Berkman et al., 2003; current pregnancy contraction monitor Iams et al., 1990; Brown et al., 1999; Nagey et al., 1993 Preterm labor in Maintenance tocolysis No benefit Berkman et al., 2003; current pregnancy (oral and Sanchez-Ramos et al., subcutaneous infusion)
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From page 276... ...
enrolled 2,422 women with an increased risk of preterm birth, including 844 women with twins, in a three-armed trial in which the participants were assigned to receive (1) education plus weekly nursing contact, (2)
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From page 277... ...
277 DIAGNOSIS AND TREATMENT OF CONDITIONS TABLE 9-6 Continued Reference Entry Criteria Antibiotics Outcome Vermeulen and Prior preterm birth Vaginal 2 percent No benefit; greater Bruinse, 1999 clindamycin versus PTD rate and placebo at 26 and infections in 32 wk of gestation compliant clindamycin group Carey et al., 2000 BV Oral metronidazole No effect in Asx women or Hx PTD ↑ PTD Klebanoff et al., 2001 Trichomonas Oral metronidazole Rosenstein, 2000 BV Vaginal clindamycin No difference in PTD Kurkinen-Raty et al,. BV at 12 wk Vaginal 2 percent No difference in 2001 of gestation clindamycin PTD Kekki et al., 2001 BV at 10–17 wk of Vaginal 2 percent No difference in gestation clindamycin versus rates of PTD placebo at 10–17 wk of gestation ↓ PTD Ugwumadu et al., BV Oral clindamycin 2003 ↓ PTD, no change Lamont et al., BV Vaginal clindamycin 2003 in rate of rate of LBW infants Andrews et al., Positive fibronectin Oral metronidazole No effect 2003 + erythromycin ↓ PTD Kiss, 2004 Gram stain for BV, Treatment of the Trichomonas, yeast organism detected Shennan et al., 2006 Clinical risk of PTB Metronidazole Study stopped due and positive fFN at to 2× increase in 24–27 wk of gestation numbers of births at <37 wk of gestation in metronidazole group NOTE: ↓ LBW = decrease in low birth weight infants; PTD = preterm delivery; ↓ PTD = decrease in rates of preterm delivery; ↑ PTD= increase in rates of preterm delivery; fFN = fetal fibronection.
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From page 278... ...
. Analysis by obstetric history of preterm birth, race-ethnicity, gestational age at the initiation of treatment, eradication of BV, and prepregnancy weight in that study did not reveal any subgroup in which treatment improved the perinatal outcome.
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From page 279... ...
. The presumed mechanism is inflammation of the nearby reproductive organs; but infections at remote sites, especially if the infection is chronic, have also been associated with an increased risk of spontaneous preterm birth.
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From page 280... ...
suggested that supplemental administration of progesterone might reduce the rate of preterm birth in women at increased risk. Two randomized placebo-controlled trials whose findings were published in 2003 found that progesterone, administered as either weekly intramuscular injections of 250 mg of 17α-hydroxprogesterone caproate (Meis et al., 2003)
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From page 281... ...
Surgical Interventions Prophylactic Cerclage for Women with a Risk of Preterm Birth Recognition that some early preterm births may be due to variant clinical presentations of cervical insufficiency led to consideration of cervical cerclage treatment for women with such a history. A randomized trial of cerclage for women with a prior preterm birth (MacNaughton et al., 1993)
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From page 282... ...
It is likely that all of these factors are operative to various degrees in an individual, but to date there is no satisfactory method to determine the contributions of physical and biochemical influences on the cervix and, thus, no way to select an appropriate therapy. The literature on the use of cerclage includes the findings of trials with women with a prior preterm birth and current ultrasound evidence of cervical effacement (Althuisius et al., 2001; Berghella et al., 2004)
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From page 283... ...
These could include, for example, studies of social interventions in women with measurable evidence of stress and studies of activity restriction in women with short cervical lengths. Finding 9-3: Studies of intervention strategies for the prevention of preterm birth have had preterm birth as their only outcome vari able.
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From page 284... ...
Diagnosis of Preterm Labor Preterm labor must be considered whenever abdominal or pelvic symptoms occur after 18 to 20 weeks of gestation. Symptoms like pelvic pressure, increased vaginal discharge, backache, and menstrual-like cramps are common with advancing pregnancy and suggest preterm labor more by their persistence than by their severity.
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From page 285... ...
. The combined use of tests for cervical length and fibronectin identifies a group of patients with a very high risk of preterm birth when the fibronectin test is positive and the sonographic cervical length is less than 30 mm (Table 9-7)
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From page 286... ...
286 TABLE 9-7 Frequency of Spontaneous Preterm Delivery According to Cervical Length (cutoff 30 mm) and Vaginal Fibronectin Results Cervical Length Fetal Delivery Within Delivery Within Delivery Within Delivery Delivery <30 mm Fibronectin + 48 Hours 7 Days 14 Days ≤32 Weeks ≤35 Weeks No No 2.2% 2.2% 3.2% 0% 1.1% (2/93)
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From page 287... ...
The mortality and morbidity of prematurely born infants are discussed in Chapter 10. Recent data from one center are shown in Figure 9-3 to illustrate how improved outcomes for infants born after 32 weeks of gestation might lead to a decision to allow preterm delivery rather than initiate treatment with drugs that may prolong the pregnancy for only a few days (Mercer, 2003)
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From page 288... ...
Finding 9-6: The knowledge and beliefs of health care providers influence their attitudes toward and their management of mothers with threatened preterm delivery and their infants. Treatment Strategies and Effectiveness The prevention of preterm birth has primarily been focused on the treatment of the woman with symptomatic preterm labor.
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From page 289... ...
This approach has not decreased the incidence of preterm birth but can delay delivery long enough to allow administration of antenatal steroids and to transfer the mother and fetus to an appropriate hospital, two interventions that have consistently been shown to reduce the rates of perinatal mortality and morbidity. Labor inhibition has not prevented preterm birth because arresting myometrial contractions does not address the specific initiators of preterm labor.
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From page 290... ...
labor. The treatment strategies used to treat women diagnosed with preterm labor are reviewed below.
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From page 291... ...
. In two randomized, placebo-controlled trials of magnesium sulfate, magnesium sulfate did not lead to improved birth outcomes, although the cessation of contractions for a short interval was demonstrated (Cox et al., 1990; Fox et al., 1993)
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From page 292... ...
. Although these protocols suppress contractions, they had no effect on the rates of preterm birth or perinatal morbidity in randomized, placebo-controlled trials (Guinn et al., 1998; Wenstrom et al., 1997)
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From page 293... ...
Eight randomized clinical trials and one nonrandomized trial have compared calcium channel blockers with beta-mimetics. In two trials, women treated with nifedipine had a longer interval between treatment and delivery and their infants had a greater mean estimated gestational age at delivery (Jannet et al., 1997; Papatsonis et al., 1997)
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From page 294... ...
In a placebo-controlled trial, the duration of pregnancy after the initiation of therapy with atosiban was not different (26 days for treated women and 21 days for women in the placebo group; p = 0.6) when the entire group of women was evaluated (gestational age, 20 to 33 weeks 6 days; n = 531)
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From page 295... ...
The surrogate or secondary outcomes used instead of neonatal morbidity are pregnancy prolongation, frequency of preterm birth, and gestational age at birth. Few placebo-controlled trials of tocolytic drugs have been conducted.
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From page 296... ...
Evidence from appropriately conducted placebo-controlled trials has shown that antibiotic treatment can reduce morbidity for infants born after PPROM and prolong the interval from rupture to delivery. A study that compared ampicillin plus erythromycin and placebo (Mercer et al., 1997)
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From page 297... ...
Betamethasone and dexamethasone are apparently equally effective in reducing perinatal morbidity, but there may be some advantage to the use of betamethasone. In a study of infants born between 24 and 31 weeks of gestation, the rate of periventricular leukomalacia was 4.4 percent among 361 infants who were treated antenatally with betamethasone, 11.0 percent among 165 infants who received dexamethasone, and 8.4 percent among 357 infants who were not treated with antenatal corticosteroids (Baud et al., 1999)
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From page 298... ...
An Australian study found a twofold increase in the numbers of infants with birth weights below the 10th percentile and a significantly reduced head circumference in infants exposed to more than three antenatal courses of steroids (French et al., 1999)
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From page 299... ...
More than 75 percent of the women in the weekly treatment group received corticosteroids within a week of preterm birth (p = 0.001) (Mercer et al., 2001a)
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From page 300... ...
Larger hospitals that care for the majority of maternal and infant complications are designated Level II centers; these hospitals have neonatal intensive care units staffed and equipped to care for most infants with birth weights between 1,250 and 1,500 grams. Level III centers typically provide care for the sickest and the smallest infants and for maternal complications requiring intensive care.
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From page 301... ...
. FUTURE DIRECTIONS Despite several interventions designed to inhibit preterm labor and prolong pregnancy, the frequency of preterm birth continues to pose a major barrier to the health of newborns worldwide.
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