Prospective, randomized, double-blind, placebo-controlled evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia.

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system. OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes. STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned expectant management. In addition to standard therapy, patients were randomized to receive either recombinant human antithrombin 250 mg loading dose followed by a continuous infusion of 2000 mg per 24 hours or an identical saline infusion until delivery. The primary outcome was days gained from randomization until delivery. The secondary outcome was composite neonatal morbidity score. A total of 120 women were randomized. RESULTS: There was no difference in median gestational age at enrollment (27.3 weeks' gestation for the recombinant human antithrombin group [range, 23.1-30.0] and 27.6 weeks' gestation for the placebo group [range, 23.0-30.0]; P=.67). There were no differences in median increase in days gained (5.0 in the recombinant human antithrombin group [range, 0-75] and 6.0 for the placebo group [range, 0-85]; P=.95). There were no differences between groups in composite neonatal morbidity scores or in maternal complications. No safety issues related to recombinant human antithrombin were noted in this study, despite the achievement of supraphysiological antithrombin concentrations. CONCLUSION: The administration of recombinant human antithrombin in preterm preeclampsia neither prolonged pregnancy nor improved neonatal or maternal outcomes.

The impact of tobacco use on preterm premature rupture of the membranes.

OBJECTIVE: To determine if tobacco use increases the incidence of preterm premature rupture of the membranes (pPROM) or alters perinatal outcomes after pPROM. STUDY DESIGN: This is a secondary analysis of the databases of three completed Eunice Kennedy Shriver National Institute of Child Health and Human Development-supported Maternal Fetal Medicine Units Network studies. Self-reported tobacco exposure data was obtained. Its relationship with the incidence of pPROM and associated neonatal outcome measures were assessed. RESULTS: There was no difference in the incidence of pPROM when comparing nonsmokers to those using tobacco. Although a trend was seen between the incidence of pPROM and the amount smoked, this did not reach statistical significance. Among the patients with pPROM, the use of tobacco was not associated with an increase in perinatal morbidity. CONCLUSION: Our data do not support a significant relationship between tobacco use and pPROM.

The antibiotic treatment of PPROM study: systemic maternal and fetal markers and perinatal outcomes.

OBJECTIVE: We sought to correlate maternal and cord blood cytokine and intercellular adhesion molecule-1 levels with antibiotic exposure and perinatal outcomes after conservatively managed preterm premature rupture of the membranes. STUDY DESIGN: Conservatively managed women with preterm premature rupture of the membranes at 24-32 weeks had blood sampling at randomization (n = 222) and delivery (n = 121). Plasma from these, and umbilical cord blood (n = 196), was stored at -70°C. Interleukin (IL)-6, IL-10, granulocyte colony-stimulating factor (G-CSF), tumor necrosis factor-α, and intercellular adhesion molecule-1 levels were assessed for associations with antibiotic treatment, latency, amnionitis, neonatal sepsis, pneumonia, and composite neonatal morbidity. RESULTS: Cord blood IL-6 and G-CSF were higher than maternal levels. Antibiotic treatment lowered only maternal G-CSF (P = .01). Elevated maternal cytokine levels were associated with delivery within 7 days and with development of chorioamnionitis. All umbilical cord blood markers were increased with amnionitis (P ≤ .01 for each). No maternal marker was associated with neonatal morbidities. Cord G-CSF and IL-6 were increased with neonatal sepsis within 72 hours of birth (P = .004 for both), and with composite neonatal morbidity (P = .001 and .002, respectively). Maternal and umbilical cord cytokine levels demonstrated low predictive values for perinatal outcomes. CONCLUSION: Umbilical cord blood cytokine values are higher than maternal levels, suggesting significant fetal/placental contribution. Maternal and umbilical cord cytokine levels are not adequately predictive to be used clinically.

Progesterone receptor polymorphisms and clinical response to 17-alpha-hydroxyprogesterone caproate.

OBJECTIVE: Seventeen-alpha-hydroxyprogesterone caproate (17-OHPC) reduces recurrent preterm birth (PTB). We hypothesized that single nucleotide polymorphisms in the human progesterone receptor (PGR) affect response to 17-OHPC in the prevention of recurrent PTB. STUDY DESIGN: We conducted secondary analysis of a study of 17-OHPC vs placebo for recurrent PTB prevention. Twenty PGR gene single nucleotide polymorphisms were studied. Multivariable logistic regression assessed for an interaction between PGR genotype and treatment status in modulating the risk of recurrent PTB. RESULTS: A total of 380 women were included; 253 (66.6%) received 17-OHPC and 127 (33.4%) received placebo. In all, 61.1% of women were African American. Multivariable logistic regression demonstrated significant treatment-genotype interactions (either a beneficial or harmful treatment response) for African Americans delivering<37 weeks' gestation for rs471767 and rs578029, and for Hispanics/Caucasians delivering<37 weeks' gestation for rs500760 and <32 weeks' gestation for rs578029, rs503362, and rs666553. CONCLUSION: The clinical efficacy and safety of 17-OHPC for recurrent PTB prevention may be altered by PGR gene polymorphisms.

Absence of mitochondrial progesterone receptor polymorphisms in women with spontaneous preterm birth.

OBJECTIVE: The truncated mitochondrial progesterone receptor (PR-M) is homologous to nuclear PRs with the exception of an amino terminus hydrophobic membrane localization sequence, which localizes PR-M to mitochondria. Given the matrilineal inheritance of both spontaneous preterm birth (SPTB) and the mitochondrial genome, we hypothesized that (a) PR-M is polymorphic and (b) PR-M localization sequence polymorphisms could result in variable progesterone-mitochondrial effects and variable responsiveness to progesterone prophylaxis. METHODS: Secondary analysis of DNA from women enrolled in a multicenter, prospective, study of 17 alpha-hydroxyprogesterone caproate (17OHPC) versus placebo for the prevention of recurrent SPTB. DNA was extracted from stored saliva. RESULTS: The PR-M localization sequence was sequenced on 344 patients. Sequences were compared with the previously published 48 base-pair sequence, and all were identical. CONCLUSIONS: We did not detect genetic variation in the mitochondrial localization sequence of the truncated PR-M in a group of women at high risk for SPTB.

Asthma in pregnancy.

Asthma is an increasingly common problem during pregnancy. Mild and moderate asthma can be associated with excellent maternal and perinatal pregnancy outcomes, especially if patients are managed according to contemporary recommendations of National Asthma Education and Prevention Program. Severe and poorly controlled asthma may be associated with increased prematurity, need for cesarean delivery, preeclampsia, and growth restriction. Severe asthma exacerbations can result in maternal morbidity and mortality, and can have commensurate adverse pregnancy outcomes. The management of asthma during pregnancy should be based upon objective assessment, trigger avoidance, patient education, and step therapy. Asthma medications should be continued during pregnancy and while breast-feeding.

The relationship of asthma-specific quality of life during pregnancy to subsequent asthma and perinatal morbidity.

OBJECTIVE: To determine whether asthma-specific quality of life during pregnancy is related to asthma exacerbations and to perinatal outcomes. METHODS: This was a secondary analysis of data from a randomized controlled trial of inhaled beclomethasone versus theophylline in the treatment of moderate asthma during pregnancy. The Juniper Asthma Quality of Life Questionnaire (AQLQ) was administered to patients at enrollment. Exacerbations were defined as asthma symptoms requiring a hospitalization, unscheduled medical visit, or oral corticosteroid course. RESULTS: Quality of life assessments were provided by 310 of the 385 participants who completed the study. There was more than a 25% decrease in the odds of a subsequent asthma exacerbation for every 1-point increase in AQLQ score for the overall score (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.55-0.96), emotion domain (OR 0.72, 95% CI 0.59-0.88), and symptoms domain (OR 0.73, 95% CI 0.57-0.94). These relationships were not significantly influenced by initial symptom frequency or forced expiratory volume in 1 s (FEV(1)). No significant relationships were demonstrated between enrollment AQLQ scores and preeclampsia, preterm birth, low birth weight, or small for gestational age. CONCLUSION: Asthma-specific quality of life in early pregnancy is related to subsequent asthma morbidity during pregnancy but not to perinatal outcomes.

The effect of active and passive household cigarette smoke exposure on pregnant women with asthma.

BACKGROUND: The article was designed to estimate the effect of active and passive household cigarette smoke exposure on asthma severity and obstetric and neonatal outcomes in pregnant women with asthma. METHODS: We used a secondary observational analysis of pregnant women with mild and moderate-severe asthma enrolled in a prospective observational cohort study of asthma in pregnancy and a randomized clinical trial (RCT) comparing inhaled beclomethasone and oral theophylline. A baseline questionnaire detailing smoking history and passive household smoke exposure was given to each patient. Smoking status was confirmed in the RCT using cotinine levels. Data on asthma severity and obstetric and neonatal outcomes were collected and analyzed with respect to self-reported tobacco smoke exposure. Kruskal-Wallis and Pearson chi(2) statistics were used to test for significance. RESULTS: A total of 2,210 women were enrolled: 1,812 in the observational study and 398 in the RCT. Four hundred and eight (18%) women reported current active smoking. Of the nonsmokers, 790 (36%) women reported passive household smoke exposure. Active smoking was associated with more total symptomatic days (P < .001) and nights of sleep disturbance (P < .001). Among the newborns of active smokers, there was a greater risk of small for gestational age < 10th percentile (P < .001), and a lower mean birth weight (P < .001). There were no differences in symptom exacerbation or outcome between nonsmokers with and without passive household cigarette smoke exposure. CONCLUSIONS: Among pregnant women with asthma, active but not passive smoking is associated with increased asthma symptoms and fetal growth abnormalities.

Maternal obesity, uterine activity, and the risk of spontaneous preterm birth.

OBJECTIVE: To assess the associations among maternal obesity, uterine contraction frequency, and spontaneous preterm birth in women at risk for spontaneous preterm birth. METHODS: In a secondary analysis, we analyzed data from 253 women at risk for spontaneous preterm birth (prior spontaneous preterm birth, vaginal bleeding) enrolled in a multicenter observational study of home uterine activity monitoring at 11 centers. All women wore a uterine activity monitor twice daily from 22 weeks through 34 weeks of gestation. Mean and maximal contractions/hour at 22-24, 25-26, 27-28, 29-30, 31-32 weeks, and at or after 33 weeks of gestation were compared between overweight/obese women (a body mass index [BMI] at 22-24 weeks greater than 25 kg/m) and normal/underweight women (a BMI of 25 kg/m or less) at each gestational age interval. Multivariable analysis evaluated the influences of BMI, contractions, fetal fibronectin, and transvaginal cervical length on spontaneous preterm birth before 35 weeks. RESULTS: Obese/overweight women (n=156) were significantly less likely to experience spontaneous preterm birth before 35 weeks (8.3% compared with 21.7%, P<.01). For each gestational age interval before 32 weeks, obese/overweight women had fewer mean contractions/hour (P<.01 for each) and maximal contractions/hour (P<.01 for each) than normal/underweight women, although their mean cervical lengths (34.3 mm compared with 33.1 mm, P=.25), and fetal fibronectin levels (7.1% compared with 7.2% 50 ng/mL or more, P=.97) were similar at study enrollment. Obese/overweight status was associated with a lower risk of spontaneous preterm birth before 35 weeks after controlling for contraction frequency and other factors evaluated at 22-24 weeks, but not at later periods. CONCLUSION: Obese/overweight women at risk for spontaneous preterm birth exhibit less uterine activity and less frequent spontaneous preterm birth before 35 weeks of gestation than normal/underweight women. LEVEL OF EVIDENCE: II.

Salivary progesterone and estriol among pregnant women treated with 17-alpha-hydroxyprogesterone caproate or placebo.

OBJECTIVE: The objectives of the study was to determine whether salivary progesterone (P) or estriol (E3) concentration at 16-20 weeks' gestation predicts preterm birth or the response to 17alpha-hydroxyprogesterone caproate (17OHPC) and whether 17OHPC treatment affected the trajectory of salivary P and E3 as pregnancy progressed. STUDY DESIGN: This was a secondary analysis of a clinical trial of 17OHPC to prevent preterm birth. Baseline saliva was assayed for P and E3. Weekly salivary samples were obtained from 40 women who received 17OHPC and 40 who received placebo in a multicenter randomized trial of 17OHPC to prevent recurrent preterm delivery. RESULTS: Both low and high baseline saliva P and E3 were associated with a slightly increased risk of preterm birth. However, 17OHPC prevented preterm birth comparably, regardless of baseline salivary hormone concentrations. 17OHPC did not alter the trajectory of salivary P over pregnancy, but it significantly blunted the rise in salivary E3 as well as the rise in the E3/P ratio. CONCLUSION: 17OHPC flattened the trajectory of E3 in the second half of pregnancy, suggesting that the drug influences the fetoplacental unit.

ACOG practice bulletin: clinical management guidelines for obstetrician-gynecologists number 90, February 2008: asthma in pregnancy.

Asthma is a common, potentially serious medical condition that complicates approximately 4-8% of pregnancies. In general, the prevalence of and morbidity from asthma are increasing, although asthma mortality rates have decreased in recent years. The purpose of this document is to review the best available evidence about the management of asthma during pregnancy.

Asthma and pregnancy.

Asthma complicates 4-8% of pregnancies. Mild and well-controlled moderate asthma can be associated with excellent maternal and perinatal pregnancy outcomes. Severe and poorly controlled asthma may be associated with increased prematurity, need for cesarean delivery, preeclampsia, growth restriction, other perinatal complications, as well as maternal morbidity and mortality. Optimal management of asthma during pregnancy includes objective monitoring of lung function, avoiding or controlling asthma triggers, patient education, and individualized pharmacologic therapy. Those with persistent asthma should be monitored by peak expiratory flow rate, spirometry to measure the forced expiratory volume in 1 second, or both. Step-care therapeutic approach uses the least amount of drug intervention necessary to control a patient's severity of asthma. Inhaled corticosteroids are the preferred treatment for the management of all levels of persistent asthma during pregnancy. It is safer for pregnant women with asthma to be treated with asthma medications than it is for them to have asthma symptoms and exacerbations. The ultimate goal of asthma therapy is maintaining adequate oxygenation of the fetus by prevention of hypoxic episodes in the mother. Asthma exacerbations should be aggressively managed, with a goal of alleviating asthma symptoms and attaining peak expiratory flow rate or forced expiratory volume in 1 second of 70% predicted or more. Pregnancies complicated by moderate or severe asthma may benefit from ultrasound for fetal growth and accurate dating and antenatal assessment of fetal well-being. Asthma medications should be continued during labor, and parturients should be encouraged to breastfeed.

A prospective masked observational study of uterine contraction frequency in twins.

OBJECTIVE: This study was undertaken to compare uterine contraction frequency in twins versus singletons and to determine if contraction frequency can be an efficient predictor of spontaneous preterm birth in twin gestations. STUDY DESIGN: Fifty-nine twin and 306 singleton gestations were enrolled between 22 and 24 weeks at 11 centers. Contraction frequency was recorded with a home uterine activity monitor (HUAM) 2 or more times per day on 2 or more days per week until delivery or 36-6/7 weeks. Masked HUAM data were interpreted according to standard protocol. Repeated measures analyses were used to determine whether mean or maximum uterine contraction frequency per hour differed between singleton and twin gestations across gestational age, by time of day, and by delivery before 35 weeks or beyond. Uterine contraction frequency was also evaluated by logistic regression and receiver operator characteristic (ROC) curves as tests to predict spontaneous preterm birth. RESULTS: There were 34,908 hours of HUAM data recorded by the 306 singleton gestations and 5,427 hours by the 59 women with twins. Uterine contraction frequency was significantly greater in twins (P = .002) compared with singletons, regardless of gestational age. Contraction frequency in twins increased significantly with gestational age and time of day (1600-0359 hours); but was not associated with spontaneous preterm birth. Maximum uterine contraction frequency was associated with preterm birth less than 35 weeks but only in the morning (am) recording (0400-1559) and at the 29- to 30-week gestational age interval. This relationship was modest (odds ratio 1-2) and not consistent across gestational age or between the am and afternoon/evening (pm) monitoring sessions. ROC analysis revealed no contraction frequency that efficiently identified twins who delivered prematurely at any 2-week gestational age interval. CONCLUSION: Mean uterine contraction frequency was significantly higher for twin gestations than singletons throughout the latter half of pregnancy and between 1600 and 0359 hours but was not higher among twins who delivered less than 35 weeks' gestation. Neither maximum am or pm contraction frequency predicted spontaneous preterm birth less than 35 weeks' gestation in twin pregnancies.

The NICHD-MFMU antibiotic treatment of preterm PROM study: impact of initial amniotic fluid volume on pregnancy outcome.

OBJECTIVE: The purpose of this study was to evaluate the associations between measured amniotic fluid volume and outcome after preterm premature rupture of membranes (PROM). STUDY DESIGN: This was a secondary analysis of 290 women, with singleton pregnancies, who participated in a trial of antibiotic therapy for preterm PROM at 24(0) to 32(0) weeks. Each underwent assessment of the 4 quadrant amniotic fluid index (AFI) and a maximum vertical fluid pocket (MVP) before randomization. The impact of low AFI (< 5.0 cm) and low MVP (< 2.0 cm) on latency, amnionitis, neonatal morbidity, and composite morbidity (any of death, RDS, early sepsis, stage 2-3 necrotizing enterocolitis, and/or grade 3-4 intraventricular hemorrhage) was assessed. Logistic regression controlled for confounding factors including gestational age at randomization, GBS carriage, and antibiotic study group. RESULTS: Low AFI and low MVP were identified in 67.2% and 46.9% of women, respectively. Delivery occurred by 48 hours, 1 and 2 weeks in 32.4%, 63.5% and 81.7% of pregnancies, respectively. Both low AFI and low MVP were associated with shorter latency (P < .001), and with a higher rate of delivery at 48 hours, 1, and 2 weeks (P = .02 for each). However, neither test offered significant additional predictive value over the risk in the total population. Low AFI and low MVP were not associated with increased amnionitis. After controlling for other factors, both low MVP and low AFI were associated with shorter latency (P < or = .002), increased composite morbidity (P = .03), and increased RDS (P < or = .01), but not with increased neonatal sepsis (P = .85) or pneumonia (P = .53). Alternatively, after controlling for fluid volume, gestational age, and GBS carriage, the antibiotic study group had longer latency, and suffered less common primary outcomes and neonatal sepsis. CONCLUSION: Oligohydramnios should not be a consideration in determining which women will be candidates for expectant management or antibiotic treatment when it is identified at initial assessment of preterm PROM remote from term.

Spirometry is related to perinatal outcomes in pregnant women with asthma.

OBJECTIVE: The purpose of this study was to test the hypothesis that maternal asthma symptoms and pulmonary function are related to adverse perinatal outcomes. STUDY DESIGN: Asthmatic patients were recruited from the 16 centers of the Maternal Fetal Medicine Units. Forced expiratory volume in 1 second was obtained at enrollment and at monthly study visits, and the frequency of asthma symptoms was assessed from enrollment to delivery. Perinatal data were obtained at postpartum chart reviews. RESULTS: The final cohort included 2123 participants with asthma. After adjustment for demographic characteristics, smoking, acute asthmatic episodes, and oral corticosteroid use, significant relationships were demonstrated between gestational hypertension and preterm birth and lower maternal gestational forced expiratory volume in 1 second. The data did not show any significant independent relationship between asthma symptom frequency and perinatal outcomes. CONCLUSION: Lower pulmonary function during pregnancy is associated with increased gestational hypertension and prematurity in the pregnancies of women with asthma, which may be due to inadequate asthma control or factors that are associated with increased asthma severity.

Outcomes of pregnancy in asthmatic women.

Mild and moderate asthma can be associated with excellent maternal and perinatal pregnancy outcomes, especially if patients are managed according to contemporary NAEPP recommendations. Severe and poorly controlled asthma may be associated with increased mild prematurity (<37 weeks' gestation), a need for cesarean delivery, preeclampsia, and growth restriction. Poorly controlled asthma and severe asthma exacerbations can result in maternal morbidity and mortality, which can have commensurate adverse pregnancy outcomes.

Does progesterone treatment influence risk factors for recurrent preterm delivery?

OBJECTIVE: To examine how demographic and pregnancy characteristics can affect the risk of recurrent preterm delivery and the how the effectiveness of progesterone treatment for prevention alters these relationships. METHODS: This was a secondary analysis of a randomized trial of 17alpha-hydroxyprogesterone caproate to prevent recurrent preterm delivery in women at risk. Associations of risk factors for preterm delivery (less than 37 completed weeks of gestation) were examined separately for the women in the 17alpha-hydroxyprogesterone caproate (n = 310) and placebo (n = 153) groups. RESULTS: Univariate analysis found that the number of previous preterm deliveries and whether the penultimate delivery was preterm were significant risk factors for preterm delivery in both the placebo and progesterone groups. High body mass index was protective of preterm birth in the placebo group. Multivariate analysis found progesterone treatment to cancel the risk of more than 1 previous preterm delivery, but not the risk associated with the penultimate pregnancy delivered preterm. Obesity was associated with lower risk for preterm delivery in the placebo group but not in the women treated with progesterone. CONCLUSION: The use of 17alpha-hydroxyprogesterone caproate in women with a previous preterm delivery reduces the overall risk of preterm delivery and changes the epidemiology of risk factors for recurrent preterm delivery. In particular, these data suggest that 17alpha-hydroxyprogesterone caproate reduces the risk of a history of more than 1 preterm delivery. LEVEL OF EVIDENCE: I.

Progesterone for prevention of recurrent preterm birth: impact of gestational age at previous delivery.

OBJECTIVE: Preterm birth occurs in 1 of 8 pregnancies and may result in significant morbidity and mortality. 17-alpha hydroxyprogesterone caproate (17-OHP caproate) has been found to be efficacious in reducing the risk of subsequent preterm delivery in women who have had a previous spontaneous preterm birth (sPTB). This analysis was undertaken to evaluate if 17-OHP caproate therapy works preferentially depending on the gestational age at previous spontaneous delivery. We hypothesized that treatment with 17-OHP caproate is more effective in prolonging pregnancy depending on the gestational age of the earliest previous preterm birth (20-27.9, 28-33.9 vs 34-36.9 weeks). STUDY DESIGN: This was a secondary analysis of 459 women with a previous sPTB enrolled in a randomized controlled trial evaluating 17-OHP caproate versus placebo. Effectiveness of 17-OHP caproate for pregnancy prolongation was evaluated based on gestational age at earliest previous delivery according to clinically relevant groupings (20-27.9, 28-33.9, and 34-36.9 weeks). Statistical analysis included the chi-square, Fisher exact, and Kruskal-Wallis tests, logistic regression, and survival analysis using proportional hazards. RESULTS: Gestational age at earliest previous delivery was similar between women treated with 17-OHP caproate or placebo (P = .1). Women with earliest delivery at 20 to 27.9 weeks and at 28 to 33.9 weeks delivered at significantly more advanced gestational age if treated with 17-OHP caproate than with placebo (median 37.3 vs 35.4 weeks, P = .046 and 38.0 vs 36.7 weeks, P = .004, respectively) and were less likely to deliver <37 weeks (42% vs 63%, P = .026 and 34% vs 56%, P = .005, respectively). Those with earliest delivery at 34 to 36.9 weeks were not significantly different between 17-OHP caproate or control. CONCLUSION: 17-OHP caproate therapy given to prevent recurrent PTB is associated with a prolongation of pregnancy overall, and especially for women with a previous spontaneous PTB at <34 weeks.

Plasma CRH measurement at 16 to 20 weeks' gestation does not predict preterm delivery in women at high-risk for preterm delivery.

OBJECTIVE: The purpose of this study was to examine the utility of a single second-trimester plasma corticotropin-releasing hormone measurement as a marker for preterm delivery in women at high risk for preterm delivery. STUDY DESIGN: This is an analysis of data from a multicenter placebo-controlled trial designed to evaluate the role of 17 alpha hydroxyprogesterone caproate (17P) in the prevention of recurrent preterm birth. Women with a documented history of a previous spontaneous preterm birth at <37 weeks were enrolled (16-20 wks) and randomly assigned in a 2 to 1 ratio to weekly injections of 17P or matching placebo. Blood was collected before treatment in 170 patients (113 assigned 17P and 57 placebo) who were enrolled at 11 of the 19 centers. Plasma levels of corticotropin-releasing hormone were compared between those who delivered preterm and those delivering at term. Data were analyzed using the Wilcoxon rank-sum test. RESULTS: The overall rates of preterm birth in this cohort of 170 patients were 35.9% at <37 weeks (31.9% progesterone, 43.9% placebo), and 19.4% at <35 weeks (18.6% vs 21.1%). The median levels of corticotropin-releasing hormone were similar between those delivering at <37 weeks and those delivering > or = 37 weeks (0.39 ng/mL vs 0.37 ng/mL, P = .08). In addition, there were no differences in corticotropin-releasing hormone levels among those who delivered at <35 weeks or > or = 35 weeks (0.36 vs 0.38, P = .90). Moreover, there were no differences in corticotropin-releasing hormone levels among those in the placebo group who delivered at <37 or > or = 37 weeks (0.40 vs 0.41, P = .72) and at <35 or > or = 35 weeks (P = .64). CONCLUSION: A single measurement of corticotropin-releasing hormone at 16 to 20 weeks' gestation is not a good biomarker for recurrent preterm delivery in patients at high risk for this complication.