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Objective: The objective of the study was to determine whether a model for predicting vaginal birth after cesarean (VBAC) can also predict the probabilty of morbidity associated with a trial of labor (TOL)., Study Design: Using a previously published prediction model, we categorized women with 1 prior cesarean by chance of VBAC. Prevalence of maternal and neonatal morbidity was stratfied by probability of VBAC success and delivery approach., Results: Morbidity became less frequent as the predicted chance of VBAC increased among women who underwent TOL (P < .001) but not elective repeat cesarean section (ERCS) (P > .05). When the predicted chance of VBAC was less than 70%, women undergoing a TOL were more likely to have maternal morbidity (relative risk [RR], 2.2; 95% confidence interval [CI], 1.5-3.1) than those who underwent an ERCS; when the predicted chance of VBAC was at least 70%, total maternal morbidity was not different between the 2 groups (RR, 0.8; 95% CI, 0.5-1.2). The results were similar for neonatal morbidity., Conclusion: A prediction model for VBAC provides information regarding the chance of TOL-related morbidity and suggests that maternal morbidity is not greater for those women who undergo TOL than those who undergo ERCS if the chance of VBAC is at least 70%.

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.

Objective: The purpose of this study was to develop a model that predicts individual-specific risk of uterine rupture during an attempted vaginal birth after cesarean delivery., Study Design: Women with 1 previous low-transverse cesarean delivery who underwent a trial of labor with a term singleton were identified in a concurrently collected database of deliveries that occurred at 19 academic centers during a 4-year period. We analyzed different classification techniques in an effort to develop an accurate prediction model for uterine rupture., Results: Of the 11,855 women who were available for analysis, 83 women (0.7%) had had a uterine rupture. The optimal final prediction model, which was based on a logistic regression, included 2 variables: any previous vaginal delivery (odds ratio, 0.44; 95% CI, 0.27-0.71) and induction of labor (odds ratio, 1.73; 95% CI, 1.11-2.69). This model, with a c-statistic of 0.627, had poor discriminating ability and did not allow the determination of a clinically useful estimate of the probability of uterine rupture for an individual patient., Conclusion: Factors that were available before or at admission for delivery cannot be used to predict accurately the relatively small proportion of women at term who will experience a uterine rupture during an attempted vaginal birth after cesarean delivery.

Objective: This study was undertaken to evaluate the effect of change of shift for physicians and nurses on complications associated with cesarean delivery., Study Design: 17,996 term women undergoing an unscheduled cesarean delivery in 13 centers from 1999-2000 were included. Maternal and neonatal morbidities were evaluated by time of infant delivery vis-à-vis nursing change of shift (6 AM-8 AM, 2 PM-4 PM, 10 PM-12 AM vs all other hours). The sample was then limited to weekdays only and physician shift changes were evaluated (physician shift change 6 AM-8 AM, 5 PM-7 PM vs all others). A composite of 30 maternal morbidities was also evaluated by logistic regression, controlling for potentially confounding factors., Results: Physician change of shift had no measurable effect on maternal and neonatal outcomes. Neonatal facial nerve palsies were increased at nursing change of shift (5 vs 0) as were hysterectomies (33 [0.24%] vs 23 [0.53%]; P < .007). Nursing change of shift had no impact on composite maternal morbidity after controlling for age, race, insurance, medical problems, prior incision type, weekend day, and prenatal care (odds ratio = 0.98; 95% confidence interval = 0.89-1.08)., Conclusion: Physician change of shift does not appear to be associated with an increase in morbidities. However, cesarean delivery during nursing change of shift is associated with increased risk of neonatal facial nerve palsy and hysterectomy. Further investigation is needed to understand the cause of this association.

Objective: The purpose of this study was to determine the impact of persistent bacterial vaginosis (BV) on the occurrence of spontaneous preterm birth (SPB) in women who test positive for fetal fibronectin., Study Design: This is a secondary analysis of a subset of pregnant women who tested positive for BV and fetal fibronectin between 16(0/7) and 25(6/7) weeks of gestation and who participated in randomized placebo controlled trials of antibiotic therapy. Nugent's criteria were used for the diagnosis of BV. Patients were reassessed for the presence of BV after treatment. The rate of SPB at <34 weeks of gestation was analyzed on the basis of treatment mode and BV status at the follow-up visit., Results: The primary studies included a total of 3285 women. A subset of 215 women met the criteria for this analysis. Seventy-seven of 100 patients (77%) in the antibiotics group vs 33 of the 115 patients (28.7%) in the placebo group became BV negative (P < .0001). The rate of SPB at <34 weeks of gestation was lower for BV resolution compared with persistent BV (0 vs 5.7%, respectively; P = .01)., Conclusion: In women who tested positive for fetal fibronectin and BV, resolution of BV is associated with less SPB before 34 weeks of gestation.

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.

Objective: Studies suggest that sleep deprivation adversely affects performance. We hypothesized that cesarean delivery complications would be more frequent during the night shift (11 pm-7 am), and evaluated morbidities by delivery shift., Study Design: Eighteen thousand nine hundred and thirty-nine term women undergoing an unscheduled cesarean delivery in 13 centers from 1999 to 2000 within a prospective observational study were included. Maternal/neonatal morbidities and time from decision to cesarean delivery were evaluated by time of delivery (7 am-3 pm, 3 pm-11 pm, 11 pm-7 am). A composite of maternal morbidities was evaluated by logistic regression controlling for potentially confounding factors., Results: Controlling for age, race, insurance, cardiac disease, preeclampsia, diabetes, previous incision type, and prenatal care, shift of delivery had no impact on maternal morbidity (11 pm-7 am OR 0.9 [95% CI 0.81-1.0]). NICU admissions were slightly increased at night but neonatal complications were not., Conclusion: Maternal and neonatal complications of cesarean delivery do not increase with delivery during the night shift.

Objective: This study was undertaken to compare success rates of vaginal birth after cesarean (VBAC) delivery, and uterine rupture as well as maternal/perinatal outcomes between women with preterm and term pregnancies undergoing trial of labor (TOL), and to compare maternal and neonatal morbidities in those women with preterm pregnancies undergoing a TOL versus repeat cesarean delivery without labor (RCD)., Study Design: Prospective 4-year observational study of women with a singleton gestation and a prior cesarean delivery at 19 academic centers. Clinical characteristics, maternal complications and VBAC delivery success for those with a preterm (24(0)-36(6) weeks) TOL, preterm RCD and term TOL (> or = 37 weeks) were analyzed., Results: Among 3119 preterm pregnancies with prior cesarean delivery, 2338 (75%) underwent a TOL. 15,331 women undergoing TOL at term were also analyzed as a control group. TOL success rates for preterm and term pregnancies were similar (72.8% vs 73.3%, P = .64). Rates of uterine rupture (0.34% vs 0.74%, P = .03) and dehiscence (0.26% vs 0.67%, P = .02) were lower in preterm compared with term TOL. Thromboembolic disease, coagulopathy and transfusion were more common in women undergoing a preterm TOL than those at term. Among women undergoing a preterm TOL, rates of uterine dehiscence, coagulopathy, transfusion, and endometritis were similar to those having a preterm RCD. After controlling for gestational age at delivery and race, neonatal outcomes such as Neonatal Intensive Care Unit (NICU) admission, intraventricular hemorrhage, sepsis, and ventilatory support were similar in both groups except for a higher rate of respiratory distress syndrome in those delivered after a TOL., Conclusion: The likelihood of VBAC success after TOL in preterm pregnancies is comparable to term gestations, with a lower risk of uterine rupture. Perinatal outcomes are similar with preterm TOL and RCD. TOL should be considered as an option for women undergoing preterm delivery with a history of prior cesarean delivery.

Objective: The purpose of this study was to determine the influence of change in infant birth weight between pregnancies on the outcome of a trial of labor for women whose first cesarean delivery was performed for dystocia., Study Design: Secondary analysis of 7081 patients with 1 previous cesarean delivery and no other deliveries after 20 weeks' gestation, undergoing a trial of labor with a singleton gestation. Cases were classified as dystocia if the listed indication for the cesarean delivery in the first pregnancy was failed induction, cephalo-pelvic disproportion, failure to progress, or failed forceps or vacuum. Outcomes of the trial of labor were correlated with fetal size relative to birth weight in the initial pregnancy for those women whose initial cesarean delivery was for dystocia and those with other indications., Results: For the cohort being studied (n = 7081), dystocia was the indication for the first cesarean delivery for 3182 (44.9%). Trial of labor resulted in vaginal delivery for 54% of patients whose first cesarean delivery was performed for dystocia, compared with 67% for those with other indications (P < .01). For those whose first cesarean delivery was for dystocia, trial of labor success was correlated with birth weight differences between the pregnancies, with only 38% delivering vaginally if the trial of labor birth weight exceeded the initial pregnancy birth weight by more than 500 g. Using logistic regression and adjusting for other potential confounding factors, the odds of success decreased by 3.8% for each increase of 100 g in birth weight in the trial of labor relative to the first birth weight., Conclusion: For women with previous cesarean delivery for dystocia, increasing birth weight in the subsequent trial of labor relative to the first birth weight diminishes the chances of successful vaginal delivery.

Objective: The purpose of this study was to determine if weekly corticosteroids improve neonatal outcome without undue harm., Study Design: Women 23 to 32 weeks receiving 1 course of corticosteroids 7 to 10 days prior were randomized to weekly betamethasone or placebo., Results: The study was terminated by the independent data and safety monitoring committee with 495 of the anticipated 2400 patients enrolled. There was no significant reduction in the composite primary morbidity outcome (8.0% vs 9.1%, P = .67). Repeated courses significantly reduced neonatal surfactant administration (P = .02), mechanical ventilation (P = .004), CPAP (P = .05), pneumothoraces (P = .03). There was no significant difference in mean birth weight or head circumference. The repeat group had a reduction in multiples of the birth weight median by gestational age (0.88 vs 0.91) (P = .01) and more neonates weighing less than the 10th percentile (23.7 vs 15.3%, P = .02). Significant weight reductions occurred for the group receiving > or = 4 courses., Conclusion: Repeat antenatal corticosteroids significantly reduce specific neonatal morbidities but do not improve composite neonatal outcome. This is accompanied by reduction in birth weight and increase in small for gestational age infants.

Objective: This study was undertaken to determine whether women with recurrent spontaneous preterm births (rSPBs) have different clinical characteristics or systemic markers than those with isolated preterm (iSPBs) or recurrent term births (rTBs), when assessed remote from delivery., Study Design: We compared clinical characteristics and findings (including cervical ultrasound, bacterial vaginosis, fetal fibronectin), maternal plasma markers obtained at 22 to 24 weeks' gestation (inflammatory cytokines, cortisol, and corticotrophin-releasing hormone), between women with rSPBs (2 or 3 consecutive SPBs and no TBs), iSPBs (1 SPB and 1 or 2 TBs), and rTBs (2 or 3 consecutive TBs and no SPBs)., Results: A total of 1257 women met our inclusion criteria; 47 rSPBs, 241 iSPBs (80 current and 161 prior iSPBs), and 969 rTBs. Before pregnancy, women with rSPBs had lower weights (P < .0001) and body mass indexes (BMIs) (P < .001), and were more likely to be less than 100 lbs (P = .008) or less than 19.8 kg/m2 BMI (P = .001). At 22 to 24 weeks those with rSPBs remained lighter and leaner, and had more advanced Bishop scores than iSPBs and rTBs. Ultrasound demonstrated progressive decrease in cervical length for those with rTBs, prior iSPBs, current iSPBs, and rSPBs, and also progressively more frequent short cervixes with worsening history (P < .001). Cervical length was shorter for women of lower pregravid weight and BMI, but not with shorter height. At 22 to 24 weeks, women with rSPBs had more common uterine contractions and tocolytic agents, but not more infections or antibiotic therapy. Those with an SPB in the current gestation had higher fetal fibronectin levels and more frequent vaginal bleeding, regardless of prior outcome. Maternal cortisol and corticotrophin-releasing hormone were higher in women with iSPBs and rSPBs than in rTB controls, (P = .001 and .0027), a finding more apparent with SPB in the current pregnancy. However, maternal cytokines were not increased with either iSPBs or rSPBs., Conclusion: Women with rSPBs are leaner, contract more, have shorter cervixes, and have more advanced Bishop scores than women with iSPBs or rTBs.

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.

Objective: The objective of the study was to estimate whether midpregnancy genitourinary tract infection with Chlamydia trachomatis is associated with an increased risk of subsequent preterm delivery., Study Design: Infection with C. trachomatis was determined using a ligase chain reaction assay (performed in batch after delivery) of voided urine samples collected at the randomization visit (16(0/7) to 23(6/7) weeks' gestation) and the follow-up visit (24(0/7) to 29(6/7) weeks) among 2470 gravide women with bacterial vaginosis or Trichomonas vaginalis infection enrolled in 2 multicenter randomized antibiotic treatment trials (metronidazole versus. placebo)., Results: The overall prevalence of genitourinary tract C. trachomatis infection at both visits was 10%. Preterm delivery less than 37 weeks' or less than 35 weeks' gestational age was not associated with the presence or absence of C. trachomatis infection at either the randomization (less than 37 weeks: 14% versus 13%, P=.58; less than 35 weeks: 6.4% versus 5.5%, P=.55) or the follow-up visit (less than 37 weeks: 13% versus 11%, P=.33; less than 35 weeks: 4.4% versus 3.7, P=.62). Treatment with an antibiotic effective against chlamydia infection was not associated with a statistically significant difference in preterm delivery., Conclusion: In this secondary analysis, midtrimester chlamydia infection was not associated with an increased risk of preterm birth. Treatment of chlamydia was not associated with a decreased frequency of preterm birth.

Objective: This study was undertaken to estimate the frequency of inflammatory cytokine and Toll-like receptor gene polymorphisms in women with and without bacterial vaginosis (BV) in pregnancy., Study Design: A secondary analysis was performed of pregnant women at less than 30 weeks' gestation enrolled as part of 2 multicenter studies. Eight hundred eighty-five women were assessed for BV (defined as Nugent's vaginal Gram stain score 7-10 and a pH > 4.5). Comparisons were made between women with or without BV. Extracted maternal DNA was analyzed for 7 cytokine (interleukin [IL] 1beta-511, IL1beta Exon 5 +3954, IL6-174, IL8-845, IL10-1082, tumor necrosis factor alpha-238 [TNFalpha-238], TNFalpha-308) and 2 Toll-like receptor (TLR-4 299, TLR-4 399) gene polymorphisms., Results: BV was diagnosed in 497 women and 388 did not have BV. Genotype and allele frequency analyses revealed associations with BV and polymorphisms at the IL1beta Exon 5 +3954, IL6-174, IL10-1082, and TLR-4 399 loci. Women with BV were less likely to be homozygous (C/C) for IL1beta Exon 5 +3954 (P = .04). Women with BV were also less likely to have polymorphisms at the IL10-1082 (P = .03) and TLR-4 399 (P = .04) loci in the univariate analysis. Women with BV were more likely to be heterozygous (G/C) for the IL6-174 genotype (P < .0001). Multivariate analysis, controlling for maternal race, confirmed the following associations with BV: IL1beta Exon 5 +3954 (odds Ratio [OR] 0.5, 95% CI 0.3-0.9) and IL6-174 (OR 2.2, 95% CI 1.6-3.1). In addition, polymorphism at the IL8-845 locus was associated with a decreased risk for BV (OR 0.6, 95% CI 0.4-1.0)., Conclusion: After controlling for race, polymorphisms at the IL1beta Exon 5 +3954, IL6-174, and IL8-845 loci were associated with an altered rate of BV in pregnancy.

Objective: The purpose of this study was to determine which factors influence the likelihood of successful trial of labor (TOL) after 1 previous cesarean delivery (CD)., Study Design: We performed a multicenter 4-year prospective observational study (1999-2002) of all women with previous CD undergoing TOL. Women with term singleton pregnancies with 1 previous low transverse CD or unknown incision were included for analysis., Results: Fourteen thousand five hundred twenty-nine women underwent TOL, with 10,690 (73.6%) achieving successful VBAC. Women with previous vaginal birth had an 86.6% success rate compared with 60.9% in women without such a history (odds ratio [OR] 4.2; 95% CI 3.8-4.5; P < .001). TOL success rates were affected by previous indication for CD, need for induction or augmentation, cervical dilation on admission, birth weight, race, and maternal body mass index. Multivariate logistic regression analysis identified as predictive of TOL success: previous vaginal delivery (OR 3.9; 95% CI 3.6-4.3), previous indication not being dystocia (CPD/FTP) (OR 1.7; 95% CI 1.5-1.8), spontaneous labor (OR 1.6; 95% CI 1.5-1.8), birth weight <4000 g (OR 2.0; 95% CI 1.8-2.3), and Caucasian race (OR 1.8, 95% CI 1.6-1.9) (all P < .001). The overall TOL success rate in obese women (BMI > or = 30) was lower (68.4%) than in nonobese women (79.6%) (P < .001), and when combined with induction and lack of previous vaginal delivery, successful VBAC occurred in only 44.2% of cases., Conclusion: Previous vaginal delivery including previous VBAC is the greatest predictor for successful TOL. Previous indication as dystocia, need for labor induction, or a maternal BMI > or = 30 significantly lowers success rates.

Objective: The purpose of this study was to define independent risk factors for uterine atony after primary cesarean delivery, and to assess their overall association with atony in the study cohort., Study Design: This was a 13-university center prospective observational study. All women who underwent primary cesarean from January 1, 1999 to December 31, 2000 were eligible. Trained and certified research nurses performed systematic data abstraction. The definition of atony required both the clinical diagnosis and the use of methergine or a prostaglandin preparation. Risk factors for uterine atony were assessed in univariable and multivariable logistic regression analyses, and these analyses then used to inform an assessment of the association of the various risk factors with the occurrence of uterine atony in the overall cohort., Results: Twenty-three thousand, three hundred and ninety pregnancies were analyzed. Uterine atony occurred in 1416 women (6%). Several variables were independently associated with atony in a multivariable model, including multiple gestation (odds ratio [OR] 2.40, 95% CI 1.95-2.93), maternal Hispanic race (2.21, 1.90-2.57), induced or augmented labor for >18 hours (2.23, 1.92-2.60), infant birth weight >4500 g (2.05, 1.53-2.69), and clinically diagnosed chorioamnionitis (1.80, 1.55-2.09). However, because the various risk factors were not very powerful, approximately half of the cases of atony were associated with the 2/3 of women lacking a given risk factor or combination of risk factors., Conclusion: Although certain risk factors and uterine atony were clearly associated, the associations are of limited practical clinical use.

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.

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.

Objective: The purpose of this study was to compare perinatal outcomes among women with conservatively treated preterm premature rupture of membranes at 24 to 32 weeks of gestation in the presence or absence of vaginal bleeding., Study Design: This is a secondary analysis of 581 women with and without vaginal bleeding within 1 week of admission with preterm premature rupture of membranes at 24 to 32 weeks of gestation who were enrolled in a multicenter trial of antibiotic therapy during conservative treatment. The main outcome was latency to delivery. Other outcome variables included clinical abruptio placentae, amnionitis, perinatal death, severe intraventricular hemorrhage, and respiratory distress syndrome., Results: Outcome data were available for 581 patients (n=50 with bleeding). Latency to delivery was not affected by the presence or absence of bleeding. In general, a history of bleeding was associated with higher frequencies of subsequently diagnosed abruptio placentae (12% vs 3.5%; P=.01), perinatal death (16% vs 4.9%; P=.006), intraventricular hemorrhage (14.3% vs 5.9%; P=.03), and respiratory distress syndrome (69.4% vs 40.4%; P<.0001), when compared with those women with nonbleeding events. Women with bleeding were less likely to be black (42% vs 60%; P=.002) and had a lower mean gestational age at preterm premature rupture of membranes (27.6 vs 28.5 weeks; P=.02) when compared with white, Hispanic, and other. After an adjustment of data was made for potentially confounding factors, women with recent bleeding were more likely to be diagnosed with abruptio placentae at delivery (odds ratio, 2.8; 95% CI, 1.03-7.8; P=.04), and their infants were more likely to have respiratory distress syndrome (odds ratio, 3.1; 95% CI, 1.5-6.6; P=.004)., Conclusion: Vaginal bleeding before preterm premature rupture of membranes is associated with increased rates of neonatal respiratory distress syndrome and abruptio placentae, but not with reduced latency to delivery.

Objective: The purpose of this study was to identify the success rates and risks in women with a twin pregnancy who attempt a trial of labor after cesarean delivery., Study Design: Cases were identified in the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network's Cesarean Registry with a woman with a twin pregnancy who had had at least 1 previous cesarean delivery., Results: During the study period (1999-2002), 412 women fulfilled the study criteria, and 226 women had elective repeat cesarean delivery. Of the 186 women (45.1% of total) who attempted a trial of labor, 120 women were delivered successfully (success rate, 64.5%), and 66 women (35.5%) had a failed trial of labor. Thirty of the failed trials of labor involved a vaginal delivery for twin A and cesarean delivery for twin B. Women who attempted a trial of labor with twins had no increased risk of transfusion, endometritis, intensive care unit admissions, or uterine rupture when compared with elective repeat cesarean delivery. Fetal and neonatal complications were uncommon in either group at>or=34 weeks of gestation., Conclusion: A trial of labor with twins after previous cesarean delivery does not appear to increase maternal morbidity. Perinatal morbidity is uncommon at>or=34 weeks of gestation.

Objective: The purpose of this study was to evaluate the relationship between prepregnancy maternal body mass index and spontaneous preterm birth and indicated preterm birth., Study Design: This was a secondary analysis of the Maternal-Fetal Medicine Units Network, Preterm Prediction study. Patients were classified into categories that were based on their body mass index. Rates of indicated and spontaneous preterm birth were compared., Results: Five hundred ninety-seven (20.5%) of 2910 women were obese. Obese women had fewer spontaneous preterm births at < 37 weeks of gestation (6.2% vs 11.2%; P < .001) and at < 34 weeks of gestation (1.5% vs 3.5%; P = .012). Women with a body mass index of < 19 kg/m2 had 16.6% spontaneous preterm birth, with a body mass index of 19 to 24.9 kg/m 2 had 11.3% spontaneous preterm birth, with a body mass index of 25 to 29.9 kg/m2 had 8.1% spontaneous preterm birth, with a body mass index of 30 to 34.9 kg/m2 had 7.1% spontaneous preterm birth, and with a body mass index of > or = 35 kg/m2 had 5.2% spontaneous preterm birth (P < .0001). Indicated delivery was responsible for an increasing proportion of preterm births with increasing body mass index (P = .001). Obese women had lower rates of cervical length < 25 mm (5% vs 8%; P = .012). Multivariable regression analysis confirmed a lower rate of spontaneous preterm birth in obese gravid women (odds ratio, 0.57; 95% CI, 0.39-0.83; P = .003)., Conclusion: Obesity before pregnancy is associated with a lower rate of spontaneous preterm birth.

Objective: It is stated commonly that the earlier in pregnancy bacterial vaginosis is diagnosed, the greater is the increase in risk of preterm birth compared with women without bacterial vaginosis. However, this contention is based on small numbers of women., Study Design: In this analysis of 12,937 women who were screened for bacterial vaginosis as part of a previously conducted clinical trial, the odds ratio of preterm birth (<7 weeks of gestation) for asymptomatic bacterial vaginosis-positive versus bacterial vaginosis-negative women was evaluated among women who were screened from 8 to 22 weeks of gestation., Results: The odds ratio of preterm birth among bacterial vaginosis-positive versus bacterial vaginosis-negative women ranged from 1.1 to 1.6 and did not vary significantly according to the gestational age at which bacterial vaginosis was screened. The odds ratio for preterm birth did not vary significantly by gestational age at diagnosis when bacterial vaginosis was subdivided into Gram stain score 7 to 8 or 9 to 10., Conclusion: Although bacterial vaginosis was associated with an increased risk of preterm birth, the gestational age at which bacterial vaginosis was screened for and diagnosed did not influence the increase.

Objective: Preterm premature rupture of the membranes (PPROM) is believed to be caused, in part, by abnormalities of collagen and increased levels of oxidative stress. Elevated homocysteine levels have been shown to induce these same pathophysiologic changes. We tested the hypothesis that serum homocysteine levels would be higher in women with PPROM when compared with matched control women., Study Design: A secondary analysis derived from 2 previously completed studies performed in the National Institutes of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. We identified 99 study cases with PPROM (24 to 32 weeks' gestation) and matched them with 99 asymptomatic control women from an observational study of preterm birth prediction. Cases and control women were matched for race, gestational age at sampling, and MFMU Network center. Serum homocysteine levels were determined by immunoassay in batch fashion by personnel masked to study arm and clinical outcomes. Serum homocysteine levels were compared between groups, as were the baseline characteristics of maternal age, cigarette smoking, nulliparity, infections during pregnancy, and body mass index (BMI) <19.8 kg/m 2. Serum homocysteine levels were dichotomized as >75th, 90th, and 95th %ile of control women, and the likelihood of elevated homocysteine levels was determined in women who smoked, had a BMI <19.8 kg/m 2, or who had PPROM. Statistical analyses included the Wilcoxon rank sum, chi-square, and Pearson correlation coefficient, where appropriate. Baseline characteristics were controlled with a logistic regression model., Results: Serum homocysteine levels measured in patients with PPROM were not significantly different from matched control women: median and (25th to 75th %ile): 4.9 (3.5-6.2) vs 4.8 (3.9-6.2 micromol/L), P =.73. In our population, neither the number of cigarettes smoked ( r = -0.08, P =.57), nor BMI ( r = -0.08, P =.24) correlated with serum homocysteine levels. The strongest association was seen in women with PPROM having serum homocysteine levels >95th %ile of control women (odds ratio [OR] 2.7, P =.10). After adjusting for baseline characteristics, no correlation between serum homocysteine level and the presence of PPROM was seen, OR 1.0 (.9-1.1); P =.99., Conclusion: Women presenting with PPROM did not have significantly increased serum homocysteine levels when compared with control women.

Objective: The purpose of this study was to evaluate the relationship between chorioamnionitis and its duration to adverse maternal, fetal, and neonatal outcomes., Study Design: This was a 13-university center, prospective observational study. All women at term carrying a singleton gestation who underwent primary cesarean from January 1, 1999 to December 31, 2000 were eligible. Data abstraction was systematic and performed by trained research nurses. Selected adverse outcomes were compared between pregnancies with, and without, clinically diagnosed chorioamnionitis using relative risks (RRs) and 95% CIs. The duration of chorioamnionitis was stratified into 5 intervals (3-6 h,>6-9 h,>9-12 h, and>12 h), and respective outcomes compared by Mantel-Haenszel test for trend. Additionally, regression analysis was used to compute odds ratios (ORs) and 95% CIs for chorioamnionitis duration length as a continuous explanatory variable., Results: 16,650 pregnancies were analyzed, 1965 (12%) with chorioamnionitis, which was associated with significantly increased risks of maternal blood transfusion, uterine atony, septic pelvic thrombophlebitis, and pelvic abscess (RR 2.3-3.7), as well as 5-minute Apgar

Objective: The purpose of this study was to determine the effectiveness of treatment over time for bacterial vaginosis in pregnancy and the probability of spontaneous resolution with placebo., Study Design: Women with asymptomatic bacterial vaginosis on Gram stain were assigned randomly at 16 to 23 weeks of gestation to receive two 2-g doses of metronidazole or placebo 48 hours apart and were re-evaluated for changes in Gram stain score on one occasion > or =2 weeks later., Results: Of 658 women who underwent metronidazole therapy, treatment was successful (score, <7) in 78% of those women who were seen at 2 to 3.9 weeks of gestation, which was similar to women seen > or =10 weeks after treatment. In 683 women who underwent placebo therapy, spontaneous resolution increased significantly from 13% at 2 to 3.9 weeks of gestation to 36% at > or =10 weeks of gestation. Spontaneous resolution was more common with lower vaginal pH or lactobacilli on Gram stain at the time of random assignment., Conclusion: The effectiveness of metronidazole therapy of bacterial vaginosis persists for > or =10 weeks. Women who underwent placebo therapy had significant remission of bacterial vaginosis over > or =10 weeks. Remission was more common when the initial vaginal microbiologic disturbances were less severe.

Objective: The study was undertaken to identify early pregnancy vaginal markers predictive of subsequent preterm birth., Study Design: In a multicenter Bacterial Vaginosis (BV) Trial, 21,554 women were screened with a vaginal pH and of these, two populations were studied. These included 12,041 who had a pregnancy outcome in the database and 6838 women who had a vaginal pH of 4.5 or greater and a Gram stain score and a pregnancy outcome in the database. ColorpHast Indicator Strips were used to determine the vaginal pH and the Nugent criteria were used to determine a vaginal Gram stain score of 0 to 10., Results: Delivery at <37, <35, or <32 weeks' gestation was similar for women with a vaginal pH of less than 4.4 or 4.7 (P not significant) but was increased in women with a pH of 5.0 (P =.04,.02,.03, respectively) or with a pH of 5.0 or greater (at each gestational age P <.0001). The effect of pH of 5.0 or greater was similar for women who had a spontaneous preterm birth at each gestational age (P <.0001) or birth weight of less than 2500 g or less than 1500 g (P <.0005). Women with a vaginal pH of 4.5 or greater and a Gram stain score of 9 to 10 (compared with 0-8) had increased preterm births at <37, <35, and <32 weeks' gestation (P <.01), and birth weights less than 2500 g (P <.0001) or less than 1500 g (P <.01). Women whose vaginal pH was 5.0 or greater had a higher prevalence of vaginal fetal fibronectin > or =50 ng/mL (P <.0001), but the proportion of women with a vaginal fetal fibronectin > or =50 mg/mL did not differ by Gram stain score., Conclusion: Women with a vaginal pH of 5.0 or greater or a vaginal pH of 4.5 or greater and a Gram stain score of 9 to 10 had significantly increased preterm births at <37, <35, and 32 weeks' gestation and/or a birth weight less than 2500 g or less than 1500 g.

Objective: The purpose of this study was to determine whether sexual intercourse was associated with the treatment efficacy or the incidence of preterm birth in two large randomized trials in which metronidazole treatment of bacterial vaginosis or Trichomonas vaginalis did not reduce preterm birth., Study Design: Secondary analysis of two multicenter, double-blind, placebo-controlled trials in which women with asymptomatic bacterial vaginosis on Gram stain or asymptomatic T vaginalis on culture were randomized at 16 to 23 weeks of gestation to metronidazole or placebo. In both studies, women took 2 g of metronidazole or placebo in the presence of a nurse (first dose) and were given a second dose to take 48 hours later. This regimen was repeated (third and fourth doses) at 24 to 29 weeks. At the time of the third dose, bacterial vaginosis and T vaginalis specimens were collected again. Patients who were randomly selected to receive metronidazole were analyzed for bacterial vaginosis and T vaginalis at 24 to 29 weeks and for preterm birth of <37 weeks of gestation, according to intercourse between first and second doses and between the second and third doses. Continuous variables were compared with the use of the Wilcoxon rank-sum test; categoric variables were compared with the use of the chi(2 ) test, Fisher exact test, or the Mantel-Haenzel test of trend., Results: Sexual intercourse between the first and second doses or between the second and third doses did not influence the incidence of bacterial vaginosis (18% vs 24%; relative risk, 0.7; 95% CI, 0.5-1.1; and 23% vs 20%; relative risk, 1.2; 95% CI, 0.9-1.6, respectively) or T vaginalis (4% vs 8%; relative risk, 0.5; 95% CI, 0.1-3.6; and 5% vs 10%; relative risk, 0.5; 95% CI, 0.2-1.1; respectively) at 24 to 29 weeks of gestation compared with no intercourse. In the T vaginalis trial, sexual intercourse between the first and second doses or between the second and third doses did not influence the incidence of preterm birth (13% vs 17%; relative risk, 0.8; 95% CI, 0.3-2.1; and 16% vs 17%; relative risk, 1.0; 95% CI, 0.6-1.6; respectively) compared with no intercourse. In the bacterial vaginosis trial, although sexual intercourse between the first and second doses did not influence the incidence of preterm birth (11% vs 12%; relative risk, 0.9; 95 % CI, 0.6-1.5), sexual intercourse between the second and third doses was associated with a reduction in the incidence of preterm birth (10% vs 16%; relative risk, 0.6; 95% CI, 0.4-0.9) compared with no intercourse., Conclusion: Sexual intercourse was associated with neither the efficacy of metronidazole treatment of bacterial vaginosis or T vaginalis nor with the incidence of preterm birth. In the bacterial vaginosis study, intercourse between the second and third doses had a negative association with preterm birth.

Objective: High levels of a number of analytes are found in maternal blood; alkaline phosphatase,alpha-fetoprotein, and corticotropin-releasing hormone have been associated with spontaneous preterm birth. We investigated the relationship between 8 potential blood markers and subsequent spontaneous preterm birth in asymptomatic pregnant women., Study Design: We performed a nested case control study that involved 127 women who were enrolled in the preterm prediction study and who had a singleton spontaneous preterm birth at <35 weeks and 127 women who had a term birth and served as matched (age, parity, center) controls. Serum that was collected at 24 and 28 weeks was analyzed for alkaline phosphatase, alpha-fetoprotein, corticotropin-releasing hormone, and 5 other analytes., Results: Alkaline phosphatase, alpha-fetoprotein, and corticotropin-releasing hormone, but not other analytes, were significantly elevated in pregnancies that ended in spontaneous preterm birth. For alkaline phosphatase at 24 weeks, the odds ratio for spontaneous preterm birth at <32 weeks was 6.8 (range, 1.4-32.8) and for spontaneous preterm birth at <35 weeks 5.1 (range, 1.7-15.6). Similar results were found at 28 weeks. For alpha-fetoprotein at 24 weeks, the odds ratio for spontaneous preterm birth at <32 weeks was 8.3 (range,2.2-30.9) and for spontaneous preterm birth at <35 weeks was 3.5 (range, 1.8-6.7). The levels at 28 weeks were still predictive but less so than at 24 weeks. Corticotropin-releasing hormone, at 28 weeks but not at 24 weeks, was predictive for spontaneous preterm birth at <35 weeks, with an odds ratio 3.4 (range, 1.0-10.9)., Conclusion: Elevated alkaline phosphatase and alpha-fetoprotein are associated with subsequent spontaneous preterm birth in asymptomatic pregnant women at 24 and 28 weeks. Elevated corticotropin-releasing hormone levels at 28 weeks are associated with spontaneous preterm birth at <35 weeks.

Objective: The purpose of this study was to determine whether follistatin-free activin A (an inhibin-related protein with rising serum levels before term labor) is associated with spontaneous preterm birth in an outpatient population., Study Design: From 10 centers, 2929 women were enrolled in the Preterm Prediction Study. Plasma was isolated from blood samples obtained at 24 and 28 weeks of gestation and stored. A nested case-controlled study was performed; there were 197 women with spontaneous preterm birth before 37 weeks of gestation with 24-week samples and 142 cases with 28-week samples that were matched to an equal number of term control samples from each time point. A follistatin-free activin A enzyme-linked immunosorbent assay was performed, with results interpreted as positive or negative (defined as a value less than the assay limit of sensitivity). A comparison of follistatin-free activin A with other tests that were associated with spontaneous preterm birth (alpha-fetoprotein, alkaline phosphatase, cortisol, granulocyte colony-stimulating factor, fetal fibronectin, and cervical interleukin-6) was also performed., Results: The odds ratio for associated spontaneous preterm birth at <37 weeks of gestation if the follistatin-free activin A result was positive was 1.16 at 24 weeks (95% CI, 0.62-2.17) and 1.39 at 28 weeks (95% CI, 0.68-2.84). A positive follistatin-free activin A result at either 24 or 28 weeks was not associated with a positive test for any of the other laboratory tests, except granulocyte colony-stimulating factor at 28 weeks' gestation., Conclusion: Follistatin-free activin A is not associated with spontaneous preterm birth in an asymptomatic outpatient population. Follistatin-free activin A may not be an appropriate screening marker for spontaneous preterm birth in the office setting.

Objective: Low serum ferritin levels correlate with low iron stores, whereas high levels are associated with an acute-phase reaction. Our objective was to determine whether elevated levels of ferritin in the genital tract may be a potent marker to identify patients at risk for spontaneous preterm delivery., Study Design: We performed a nested case-control study involving 182 women who had spontaneous preterm delivery and 182 term control subjects matched for race, parity, and recruitment center, and selected from 2929 women enrolled in the Preterm Prediction Study of the National Institute of Child Health and Development Maternal-Fetal Medicine Units Network. Cervical fluid ferritin was measured by use of radioimmunoassay., Results: Cervical ferritin levels were significantly higher in women who subsequently had spontaneous early preterm delivery (<32 weeks, mean +/- SD, 37.7 +/- 31.1 vs 21.5 +/- 24.1 ng/mL, P =.002; and <35 weeks, 43.2 +/- 62.7 vs 28.2 +/- 36.7 ng/mL, P =.004) than in term controls. A cervical ferritin of >75th percentile in the controls (>35.5 ng/mL) was found in 52.9% (9/17) of the women delivered <29 weeks vs 17.7% (3/17) of the controls (odds ratio [OR] 5.3 [95% CI 1.1-25.2]) and in 43.5% (20/46) of the women delivered <32 weeks versus 10.9% (5/46) of the controls (OR 6.3, 95% CI 2.1-18.9). Cervical ferritin levels had a weaker association with spontaneous preterm delivery <35 weeks (OR 2.8 [95% CI 1.5-5.1]) and <37 weeks (OR 1.6, 95% CI 1.0-2.5]). Cervical ferritin levels correlated significantly with cervical lactoferrin, interleukin-6 (IL-6), and defensin levels., Conclusions: Elevated cervical ferritin levels at 22 to 24 weeks of gestation in asymptomatic women are associated with subsequent spontaneous preterm birth. The strong correlation of cervical ferritin with other inflammatory markers provides support for the hypothesis of infection as a mediator of preterm delivery.