Search

Remarkable changes must occur in the pelvic floor muscles and tissues comprising the birth canal to allow vaginal delivery. Despite these preparatory adaptations, approximately 13% of women who deliver vaginally for the first time (nulliparas) sustain tears near the origin of the pubovisceral muscle (PVM) which can result in pelvic organ prolapse later in life. To investigate why these tears occur, it is necessary to quantify the viscoelastic behavior of the term pregnant human birth canal. The goal of this study was to quantify the in vivo material properties of the human birth canal, in situ, during the first stage of labor and compare them to published animal data. The results show that pregnant human, ovine and squirrel monkey birth canal tissue can be characterized by the same set of constitutive relations; the interspecies differences were primarily explained by the long time constant, τ 2 , with its values of 555s, 1110s, and 2777s, respectively. Quantification of these viscoelastic properties should allow for improved accuracy of computer models aimed at understanding birth-related injuries., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Infants born <37 weeks' gestation are of public health concern since complications associated with preterm birth are the leading cause of mortality in children <5 years of age and a major cause of morbidity and lifelong disability. The administration of 17-alpha hydroxyprogesterone caproate reduces preterm birth by 33% in women with history of spontaneous preterm birth. We demonstrated previously that plasma concentrations of 17-alpha hydroxyprogesterone caproate vary widely among pregnant women and that women with 17-alpha hydroxyprogesterone caproate plasma concentrations in the lowest quartile had spontaneous preterm birth rates of 40% vs rates of 25% in those women with higher concentrations. Thus, plasma concentrations are an important factor in determining drug efficacy but the reason 17-alpha hydroxyprogesterone caproate plasma concentrations vary so much is unclear. Predominantly, 17-alpha hydroxyprogesterone caproate is metabolized by CYP3A4 and CYP3A5 enzymes., Objective: We sought to: (1) determine the relation between 17-alpha hydroxyprogesterone caproate plasma concentrations and single nucleotide polymorphisms in CYP3A4 and CYP3A5; (2) test the association between progesterone receptor single nucleotide polymorphisms and spontaneous preterm birth; and (3) test whether the association between plasma concentrations of 17-alpha hydroxyprogesterone caproate and spontaneous preterm birth varied by progesterone receptor single nucleotide polymorphisms., Study Design: In this secondary analysis, we evaluated genetic polymorphism in 268 pregnant women treated with 17-alpha hydroxyprogesterone caproate, who participated in a placebo-controlled trial to evaluate the benefit of omega-3 supplementation in women with history of spontaneous preterm birth. Trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were measured between 25-28 weeks of gestation after a minimum of 5 injections of 17-alpha hydroxyprogesterone caproate. We extracted DNA from maternal blood samples and genotyped the samples using TaqMan (Applied Biosystems, Foster City, CA) single nucleotide polymorphism genotyping assays for the following single nucleotide polymorphisms: CYP3A4*1B, CYP3A4*1G, CYP3A4*22, and CYP3A5*3; and rs578029, rs471767, rs666553, rs503362, and rs500760 for progesteronereceptor. We adjusted for prepregnancy body mass index, race, and treatment group in a multivariable analysis. Differences in the plasma concentrations of 17-alpha hydroxyprogesterone caproate by genotype were evaluated for each CYP single nucleotide polymorphism using general linear models. The association between progesterone receptor single nucleotide polymorphisms and frequency of spontaneous preterm birth was tested using logistic regression. A logistic model also tested interaction between 17-alpha hydroxyprogesterone caproate concentrations with each progesterone receptor single nucleotide polymorphism for the outcome of spontaneous preterm birth., Results: The association between CYP single nucleotide polymorphisms *22, *1G, *1B, and *3 and trough plasma concentrations of 17-alpha hydroxyprogesterone caproate was not statistically significant (P = .68, .44, .08, and .44, respectively). In an adjusted logistic regression model, progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 were not associated with the frequency of spontaneous preterm birth (P = .29, .10, .76, .09, and .43, respectively). Low trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were statistically associated with a higher frequency of spontaneous preterm birth (odds ratio, 0.78; 95% confidence ratio, 0.61-0.99; P = .04 for trend across quartiles), however no significant interaction with the progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 was observed (P = .13, .08, .10, .08, and .13, respectively)., Conclusion: The frequency of recurrent spontaneous preterm birth appears to be associated with trough 17-alpha hydroxyprogesterone caproate plasma concentrations. However, the wide variation in trough 17-alpha hydroxyprogesterone caproate plasma concentrations is not attributable to polymorphisms in CYP3A4 and CYP3A5 genes. Progesterone receptor polymorphisms do not predict efficacy of 17-alpha hydroxyprogesterone caproate. The limitations of this secondary analysis include that we had a relative small sample size (n = 268) and race was self-reported by the patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The US Preventive Services Task Force recommends low-dose aspirin for the prevention of preeclampsia among women at high risk for primary occurrence or recurrence of disease. Recommendations for the use of aspirin for preeclampsia prevention were issued by the US Preventive Services Task Force in September 2014., Objectives: The objective of the study was to evaluate the incidence of recurrent preeclampsia in our cohort before and after the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention., Study Design: This was a retrospective cohort study designed to evaluate the rates of recurrent preeclampsia among women with a history of preeclampsia. We utilized a 2-hospital, single academic institution database from August 2011 through June 2016. We excluded multiple gestations and included only the first delivery for women with multiple deliveries during the study period. The cohort of women with a history of preeclampsia were divided into 2 groups, before and after the release of the US Preventive Services Task Force 2014 recommendations. Potential confounders were accounted for in multivariate analyses, and relative risk and adjusted relative risk were calculated., Results: A total of 17,256 deliveries occurred during the study period. A total of 417 women had a documented history of prior preeclampsia: 284 women before and 133 women after the US Preventive Services Task Force recommendation. Comparing the before and after groups, the proportion of Hispanic women in the after group was lower and the method of payment differed between the groups (P <.0001). The prevalence of type 1 diabetes was increased in the after period, but overall rates of pregestational diabetes were similar (6.3% before vs 5.3% after [P > .05]). Risk factors for recurrent preeclampsia included maternal age >35 years (relative risk, 1.83; 95% confidence interval, 1.34-2.48), Medicaid insurance (relative risk, 2.08; 95% confidence interval, 1.15-3.78), type 2 diabetes (relative risk, 2.13; 95% confidence interval, 1.37-3.33), and chronic hypertension (relative risk, 1.96; 95% confidence interval, 1.44-2.66). The risk of recurrent preeclampsia was decreased by 30% in the after group (adjusted relative risk, 0.70; 95% confidence interval, 0.52-0.95)., Conclusion: Rates of recurrent preeclampsia among women with a history of preeclampsia decreased by 30% after release of the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. Future prospective studies should include direct measures of aspirin compliance, gestational age at initiation, and explore the influence of race and ethnicity on the efficacy of this primary prevention., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Gestational diabetes mellitus (GDM) is one of most common complications of pregnancy, with incidence rates varying by maternal age, race/ethnicity, obesity, parity, and family history. Given its increasing prevalence in recent decades, covariant environmental and sociodemographic factors may be additional determinants of GDM occurrence., Objective: We hypothesized that environmental risk factors, in particular measures of the food environment, may be a diabetes contributor. We employed geospatial modeling in a populous US county to characterize the association of the relative availability of fast food restaurants and supermarkets to GDM., Study Design: Utilizing a perinatal database with >4900 encoded antenatal and outcome variables inclusive of ZIP code data, 8912 consecutive pregnancies were analyzed for correlations between GDM and food environment based on countywide food permit registration data. Linkage between pregnancies and food environment was achieved on the basis of validated 5-digit ZIP code data. The prevalence of supermarkets and fast food restaurants per 100,000 inhabitants for each ZIP code were gathered from publicly available food permit sources. To independently authenticate our findings with objective data, we measured hemoglobin A1c levels as a function of geospatial distribution of food environment in a matched subset (n = 80)., Results: Residence in neighborhoods with a high prevalence of fast food restaurants (fourth quartile) was significantly associated with an increased risk of developing GDM (relative to first quartile: adjusted odds ratio, 1.63; 95% confidence interval, 1.21-2.19). In multivariate analysis, this association held true after controlling for potential confounders (P = .002). Measurement of hemoglobin A1c levels in a matched subset were significantly increased in association with residence in a ZIP code with a higher fast food/supermarket ratio (n = 80, r = 0.251 P < .05)., Conclusion: As demonstrated by geospatial analysis, a relationship of food environment and risk for gestational diabetes was identified., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to examine the association between gestational age (GA) at the time of treatment initiation for gestational diabetes mellitus (GDM) and maternal and perinatal outcomes., Study Design: We conducted a secondary analysis of a multicenter randomized treatment trial of mild GDM in which women with mild GDM were assigned randomly to treatment vs usual care. The primary outcome of the original trial, as well as this analysis, was a composite perinatal adverse outcome that included neonatal hypoglycemia, hyperbilirubinemia, hyperinsulinemia, and perinatal death. Other outcomes that were examined included the frequency of large for GA, birthweight, neonatal intensive care unit admission, gestational hypertension/preeclampsia, and cesarean delivery. The interaction between GA at treatment initiation (stratified as 24-26, 27, 28, 29, and ≥30 weeks of gestation) and treatment group (treated vs routine care), with the outcomes of interest, was used to determine whether GA at treatment initiation was associated with outcome differences., Results: Of 958 women whose cases were analyzed, those who initiated treatment at an earlier GA did not gain an additional treatment benefit compared with those who initiated treatment at a later GA (probability value for interaction with the primary outcome, .44). Similarly, there was no evidence that other outcomes were improved significantly by earlier initiation of GDM treatment (large for GA, P = .76; neonatal intensive care unit admission, P = .8; cesarean delivery, P = .82). The only outcome that had a significant interaction between GA and treatment was gestational hypertension/preeclampsia (P = .04), although there was not a clear cut GA trend where this outcome improved with treatment., Conclusion: Earlier initiation of treatment of mild GDM was not associated with stronger effect of treatment on perinatal outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: We sought to compare weight loss in the first 6 weeks postpartum among women with gestational diabetes mellitus (GDM) treated with metformin or placebo, a promising therapy to reduce later risk of progression to diabetes mellitus., Study Design: We conducted a pilot, randomized trial of metformin vs placebo in postpartum women with GDM. Women with pre-GDM, unable to tolerate metformin, resumed on insulin or oral hypoglycemic agent, delivered <34 weeks' gestation, or with a body mass index <20 kg/m(2) were excluded. Women were randomized to either metformin 850 mg daily for 7 days, then metformin 850 mg twice a day for the next 5 weeks or placebo prescribed in a similar frequency. The subject, health care provider, and research staff were blinded to the treatment. The primary outcome was weight change from delivery to 6 weeks postpartum. Secondary outcomes included the percentage of women achieving their self-reported prepregnancy weight, reported medication adherence, adverse effects, and satisfaction. Differences in weight change between groups were determined by Wilcoxon rank sum test and in achieving prepregnancy weight by χ(2) test., Results: Of 114 women randomized, 79 (69.3%) completed the 6 weeks; 36 (45.6%) were randomized to metformin and 43 (54.4%) to placebo. Metformin and placebo groups were similar in median weight loss (6.3 kg [range, -0.3 to 19.8] vs 6.5 kg [range, -0.3 to 12.1], P = .988) and percentage of women achieving reported prepregnancy weight (41.7 vs 37.2%, P = .69). Self-reported adherence in taking >50% of medication was 75% at 3 weeks and 97% at 6 weeks. Nausea, diarrhea, and hypoglycemia were reported in approximately 11-17% of women and 56-63% reported dissatisfaction with the medication., Conclusion: Women with GDM lost approximately 6 kg by 6 weeks' postpartum. This was similar in both groups and resulted in <50% of women achieving their prepregnancy weight. Although the reported adherence and satisfaction with the medication was high, adverse effects were reported with nearly 1 in 5 women including nausea, diarrhea, and hypoglycemia. Contrary to expectation, we found no evidence of benefit from metformin. However, longer treatment periods and larger studies with minimal attrition may be warranted., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to evaluate the relationship between gestational age (GA) and induction of labor (IOL) and the rate of cesarean delivery in women with mild gestational diabetes mellitus., Study Design: We conducted a secondary analysis of data from a multicenter randomized controlled trial of mild gestational diabetes mellitus treatment. Cesarean delivery rate of women delivering at term (≥37 weeks' gestation) was evaluated by 2 complementary approaches: (1) IOL vs spontaneous labor: women who were induced at each GA compared with those who spontaneously labored at the same GA and (2) IOL vs expectant management: women who delivered after IOL at each GA compared with those who delivered after spontaneous labor at the same GA or subsequently after spontaneous or induced labor (outcome at each week compared with expectant management at that week). Logistic regression adjusted for potential confounders., Results: The overall cesarean delivery rate was 13%. When compared with 39 weeks' gestation (either IOL or spontaneous labor) as the referent, there was no significant difference in the cesarean delivery rate in women who delivered at 37, 38, or 40 weeks' gestation. However, IOL was associated with a 3-fold increase in cesarean delivery rate at 41 weeks' gestation and beyond, as compared with IOL at 39 weeks' gestation. Similarly, there was a 3-fold increase in the cesarean delivery rate in women who were induced when compared with those who were treated expectantly at 40 completed weeks' gestation., Conclusion: Induction of labor in women with mild gestational diabetes mellitus does not increase the rate of cesarean delivery at <40 weeks' gestation., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: We sought to evaluate inadequate gestational weight gain and fetal growth among overweight and obese women., Study Design: We conducted an analysis of prospective singleton term pregnancies in which 1053 overweight and obese women gained >5 kg (14.4 ± 6.2 kg) or 188 who either lost or gained ≤5 kg (1.1 ± 4.4 kg). Birthweight, fat mass, and lean mass were assessed using anthropometry. Small for gestational age (SGA) was defined as ≤10th percentile of a standard US population. Univariable and multivariable analysis evaluated the association between weight change and neonatal morphometry., Results: There was no significant difference in age, race, smoking, parity, or gestational age between groups. Weight loss or gain ≤5 kg was associated with SGA, 18/188 (9.6%) vs 51/1053 (4.9%); (adjusted odds ratio, 2.6; 95% confidence interval, 1.4-4.7; P = .003). Neonates of women who lost or gained ≤5 kg had lower birthweight (3258 ± 443 vs 3467 ± 492 g, P < .0001), fat mass (403 ± 175 vs 471 ± 193 g, P < .0001), and lean mass (2855 ± 321 vs 2995 ± 347 g, P < .0001), and smaller length, percent fat mass, and head circumference. Adjusting for diabetic status, prepregnancy body mass index, smoking, parity, study site, gestational age, and sex, neonates of women who gained ≤5 kg had significantly lower birthweight, lean body mass, fat mass, percent fat mass, head circumference, and length. There were no significant differences in neonatal outcomes between those who lost weight and those who gained ≤5 kg., Conclusion: In overweight and obese women weight loss or gain ≤5 kg is associated with increased risk of SGA and decreased neonatal fat mass, lean mass, and head circumference., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: Endogenous digoxin-like factor (EDLF) has been linked to vasoconstriction, altered membrane transport, and apoptosis. Our objective was to determine whether increased EDLF in the cord sera of preterm infants was associated with an increased incidence of necrotizing enterocolitis (NEC)., Study Design: Cord sera from pregnant women enrolled in a randomized trial of MgSO4 for fetal neuroprotection were analyzed for EDLF using a red cell Rb(+) uptake assay in which the inhibition of sodium pump-mediated Rb(+) transport was used as a functional assay of EDLF. Specimens were assayed blinded to neonatal outcome. Cases (NEC, n = 25) and controls (neonates not developing stage 2 or 3 NEC, n = 24) were matched by study center and gestational age. None of the women had preeclampsia. Cases and controls were compared using the Wilcoxon test for continuous and the Fisher exact test for categorical variables. A conditional logistic regression analysis was used to assess the odds of case vs control by EDLF level., Results: Cases and controls were not significantly different for gestational age, race, maternal steroid use, premature rupture of membranes, or MgSO4 treatment. In logistic models adjusted for treatment group, race, premature rupture of membranes, and gestational age, cord sera EDLF was significantly associated with development of NEC (P = .023)., Conclusion: These data demonstrated an association between cord sera EDLF and NEC., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: The objective of this study was to determine the fetal drug compartment concentrations when various concentrations of carboplatin cross the placental-trophoblastic barrier and the effect on the fetal kidneys., Study Design: An ex vivo human placenta perfusion model was utilized. Term human placentae (n = 9) were collected immediately after delivery and then reperfused with plasma concentrations achieved with carboplatin an area under the curve of 5 (1000 ng/mL), 7.5 (5000 ng/mL), or 11 (11,000 ng/mL). Antipyrine was used as a reference compound. Samples were collected over 2 hours. Placental transfer was evaluated by computation of transport fraction and clearance index. Primary cells isolated by explant culture of 16-18 week old fetal organ tissues were incubated with carboplatin for up to 48 hours with untreated cell as controls. Immunohistochemical, flow cytometry analysis, and immunoblotting were applied for the expression of apoptosis-related proteins., Results: Mean transport fractions for carboplatin at low, middle, and high concentrations were 0.05 ± 0.02, 0.04 ± 0.01, and 0.10 ± 0.01, respectively, with clearance indexes of 0.22 ± 0.01, 0.14 ± 0.08, and 0.50 ± 0.07, respectively. The fetal peak concentrations of carboplatin achieved were 61 ± 39 ng/mL (low), 375 ± 248 ng/mL (middle), and 2081 ± 529 ng/mL (high). Fetal kidney cells exposed to carboplatin showed a concentration-dependent increased expression of apoptosis-inducing factor and p53 apoptosis proteins and a time-dependent increase in expression Bax apoptosis protein expression. Apoptosis was confirmed at the high concentration by flow cytometry., Conclusion: Doses of carboplatin up to an area under the curve of 7.5 were not associated with significant placental transfer, fetal exposure, or fetal toxic effects. This suggests it might not be necessary to empirically reduce carboplatin doses in pregnant women., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: Lipoproteins are associated with atherogenic and inflammatory processes, and these processes may be related to adverse pregnancy outcomes. We therefore examined whether variations in lipoprotein particle size and concentration are associated with preterm birth (PTB) <35 weeks' gestation., Study Design: This is a case-control ancillary study to a randomized trial of omega-3 fatty acid supplementation to prevent recurrent PTB. We measured standard lipids and used nuclear magnetic resonance (NMR) spectroscopy to characterize 17 lipoprotein particles from plasma collected at the baseline randomization visit (16-21 weeks' gestation) in 128 cases (PTB <35 weeks' gestation) and 132 term controls. Logistic regression models controlled for study center, race/ethnicity, number of prior PTB, smoking, and treatment group, as well as total low-density lipoprotein (LDL), high-density lipoprotein, and triglyceride concentrations when examining LDLNMR, high-density lipoproteinNMR, and very LDL (VLDL)NMR, respectively., Results: Only 1 of the 17 NMR lipoproteins was associated with recurrent PTB. We observed an increased odds of recurrent PTB of 1.04 (95% confidence interval, 1.01-1.08; P = .02) per nanometer increase in VLDLNMR particle size and an odds ratio of 3.00 (confidence interval, 1.40-6.43; P = .005) for the third tertile of VLDLNMR particle size compared with the first tertile., Conclusion: In women with prior PTB, variations in midpregnancy lipoproteins were not associated with recurrent PTB overall, however the association observed with VLDLNMR particle size is suggestive that PTB may be amenable to lifestyle, nutritional, or pharmacologic interventions., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: The purpose of this study was to estimate a gestational age threshold at which the benefits of treatment with weekly courses of antenatal corticosteroids (ACS) during preterm labor outweigh the risks., Study Design: Risk-benefit ratios by gestational age were determined with the use of a Markov microsimulation decision-analysis model with a 1-week cycle length. Single course and multiple (weekly to a maximum of 4) courses of ACS by gestational age of entry (23 weeks to 31 weeks 6 days' gestation) were compared. Benefits were composite events (respiratory distress syndrome, chronic lung disease, severe intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, or stillbirth) averted. Risks were small head circumference and small for gestational age., Results: More composite events are averted (benefits) than risks acquired (ratio, 6:1) when multiple courses of ACS are initiated at 26 weeks' gestation. When multiple courses of ACS are initiated at 29 weeks' gestation, the risk-benefit ratio is 1. Beyond 29 weeks, there is a suggestion of more risk than benefit., Conclusion: The model suggests that multiple courses of ACS that are initiated at <29 weeks' gestation may have increased benefit compared with risks. Further analyses are needed to determine the long-term clinical significance of these findings., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: The objective of the study was to determine whether an individualized growth standard (IS) improves the identification of preterm small-for-gestational-age (SGA) neonates at risk of developing moderate/severe cerebral palsy (CP) or death., Study Design: This study was a secondary analysis of data from a randomized trial of MgSO4 for the prevention of CP or death among anticipated preterm births. Singleton nonanomalous liveborns delivered before 34 weeks' were classified as SGA (less than the 10th percentile for their gestational age) by a population standard (PS) or an IS (incorporating maternal age, height, weight, parity, race/ethnicity, and neonatal sex). The primary outcome was the prediction of moderate or severe CP or death by age 2 years., Results: Of 1588 eligible newborns, 143 (9.4%) experienced CP (n = 33) or death (n = 110). Forty-four (2.8%) were SGA by the PS and 364 (22.9%) by the IS. All PS-SGA newborns also were identified as IS-SGA. SGA newborns by either standard had a similarly increased risk of CP or death (PS: relative risk [RR], 2.4, 95% confidence interval [CI], 1.3-4.3 vs IS: RR, 1.8, 95% CI, 1.3-2.5, respectively). The similarity of RRs remained after stratification by the MgSO4 treatment group. The IS was more sensitive (36% vs 6%, P < .001) but less specific (78% vs 98%, P < .001) for CP or death. The receiver operating characteristic curve analysis revealed a statistically lower area under the curve for the PS, although the ability of either method to predict which neonates would subsequently develop CP or death was poor (PS: 0.55, 95% CI, 0.49-0.60 vs IS: 0.59, 95% CI, 0.54-0.64, P < .001)., Conclusion: An individualized SGA growth standard does not improve the association with, or prediction of, CP or death by age 2 years., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To estimate the cost-effectiveness of a trial of labor after one previous cesarean (TOLAC) when incorporating long-term events and outcomes., Methods: A Markov model comparing TOLAC with elective repeat cesarean delivery (ERCD) was developed for a hypothetical cohort with no contraindication to a TOLAC. Women were selected from a prospective study to derive probability estimates for potential events through three subsequent pregnancies. Probabilities for cerebral palsy and stress urinary incontinence, cost data, and quality-adjusted life-years (QALYs) were obtained from the literature. The primary outcome was cost-effectiveness measured as the marginal cost per QALY gained, with a $50,000 threshold per QALY used to define cost-effectiveness., Results: The TOLAC strategy dominated the ERCD strategy at baseline, with $164.2 million saved and 500 QALYs gained per 100,000 women. The model was sensitive to six variables: the probability of uterine rupture and successful TOLAC among women with no prior vaginal delivery, the frequency of stress urinary incontinence, and the costs of failed TOLAC, successful TOLAC, and ERCD. When the probability of TOLAC success was at the base value, 67.2%, TOLAC was preferred if the probability of uterine rupture was 3.1% or less. When the probability of uterine rupture was at the base value, 0.8%, the TOLAC strategy was preferred as long as the probability of success was 47.2% or more. Probabilistic sensitivity analysis confirmed the base-case analysis., Conclusions: Under baseline circumstances, TOLAC is less expensive and more effective than an ERCD when considering long-term consequences when the likelihood of success is 47.2% or more., (Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.)

Objective: To determine the relation between thrombin generation (measured by thrombin-antithrombin [TAT] complexes) early in pregnancy and subsequent preterm delivery., Study Design: Select cohort of 731 women undergoing indicated second trimester amniocentesis prospectively followed to delivery. Primary outcome was preterm delivery. TAT levels were examined continuously and categorized by quartiles. Multivariable techniques were applied to adjust for potential confounders. Receiver operating characteristic curve analysis was used to determine a discriminatory cutoff level for TAT complexes., Results: TAT concentration was significantly higher in women who delivered preterm (median, 98.9 mcg/L) than in those who did not (median, 66.3 mcg/L; P < .001). This difference persisted when 55 spontaneous preterm deliveries (median, 87.6 mcg/L) and 34 indicated preterm deliveries (median, 117.7 mcg/L) were separately compared with controls (P = .04 and P < .001, respectively). Crude and adjusted odds ratio for preterm delivery in the upper 2 TAT quartiles relative to the uppermost quartile relative to the lowest quartile were 2.45 (95% confidence interval [CI], 1.36-4.72; P = .004) and 2.31 (95% CI, 1.18-4.65; P = .017), respectively. Despite these distinct differences, the area under the receiver operating characteristic curve was only 0.62 (95% CI, 0.56-0.69), indicating poor performance of TAT concentration as a risk discriminator., Conclusion: Amniotic fluid levels of TAT complexes in the second trimester are elevated in women who subsequently deliver preterm, suggesting that thrombin generation may be involved in the various etiopathogenic mechanisms leading to preterm delivery., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: We sought to evaluate in women with twin gestation the relationship between 17-hydroxyprogesterone caproate (17-OHPC) concentration and gestational age at delivery and select biomarkers of potential pathways of drug action., Study Design: Blood was obtained between 24-28 weeks (epoch 1) and 32-35 weeks (epoch 2) in 217 women with twin gestation receiving 17-OHPC or placebo. Gestational age at delivery and concentrations of 17-OHPC, 17-hydroxyprogesterone, progesterone, C-reactive protein (CRP), and corticotrophin-releasing hormone were assessed., Results: Women with higher concentrations of 17-OHPC delivered at earlier gestational ages than women with lower concentrations (P < .001). Women receiving 17-OHPC demonstrated significantly higher (P = .005) concentrations of CRP in epoch 1 than women receiving placebo but CRP values were similar in epoch 2 in both groups. A highly significant (P < .0001) positive relationship was observed between 17-OHPC concentration and progesterone and 17-hydroxyprogesterone concentrations at both epochs. Corticotropin-releasing hormone concentrations did not differ by treatment group., Conclusion: 17-OHPC may adversely impact gestational age at delivery in women with twin gestation., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: The purpose of this study was to estimate the association of pregravid body mass index (BMI), independent of 3-hour oral glucose tolerance test (OGTT) results, with pregnancy outcome., Study Design: In this secondary analysis of a cohort of women with untreated mild gestational glucose intolerance, which was defined as a 50-g glucose loading test between 135 and 199 mg/dL and fasting glucose level of <95 mg/dL, we modeled the association between pregravid BMI, OGTT results, and both pregnancy complications and neonatal adiposity., Results: Among 1250 participants, both pregravid BMI and glucose at hour 3 of the OGTT were associated with increased risk of gestational hypertension. Maternal pregravid BMI also was associated positively with large-for-gestational-age infants; both maternal BMI and fasting glucose were associated with birthweight z-score and neonatal fat mass., Conclusion: Among women with untreated mild gestational glucose intolerance, pregravid BMI is associated with increased gestational hypertension, birthweight, and neonatal fat mass, independent of OGTT values., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: We evaluated whether improvements in pregnancy outcomes after treatment of mild gestational diabetes mellitus differed in magnitude on the basis of fetal gender., Study Design: This is a secondary analysis of a masked randomized controlled trial of treatment for mild gestational diabetes mellitus. The results included preeclampsia or gestational hypertension, birthweight, neonatal fat mass, and composite adverse outcomes for both neonate (preterm birth, small for gestational age, or neonatal intensive care unit admission) and mother (labor induction, cesarean delivery, preeclampsia, or gestational hypertension). After stratification according to fetal gender, the interaction of gender with treatment status was estimated for these outcomes., Results: Of the 469 pregnancies with male fetuses, 244 pregnancies were assigned randomly to treatment, and 225 pregnancies were assigned randomly to routine care. Of the 463 pregnancies with female fetuses, 233 pregnancies were assigned randomly to treatment, and 230 pregnancies were assigned randomly to routine care. The interaction of gender with treatment status was significant for fat mass (P = .04) and birthweight percentile (P = .02). Among women who were assigned to the treatment group, male offspring were significantly more likely to have both a lower birthweight percentile (50.7 ± 29.2 vs 62.5 ± 30.2 percentile; P < .0001) and less neonatal fat mass (487 ± 229.6 g vs 416.6 ± 172.8 g; P = .0005,) whereas these differences were not significant among female offspring. There was no interaction between fetal gender and treatment group with regard to other outcomes., Conclusion: The magnitude of the reduction of a newborn's birthweight percentile and neonatal fat mass that were related to the treatment of mild gestational diabetes mellitus appears greater for male neonates., (Copyright © 2012. Published by Mosby, Inc.)

Objective: We sought to determine if second-trimester amniotic fluid thrombin-antithrombin (TAT) complexes concentration correlates with subsequent preterm birth., Study Design: A cohort of 550 women with singleton nonanomalous pregnancies undergoing second-trimester genetic amniocentesis was followed up to delivery and analyzed as a nested case-control study. Cases of preterm birth (n = 52) were compared with 104 term control subjects. Amniotic fluid collected at amniocentesis was tested for TAT., Results: TAT concentrations were significantly higher in women who delivered preterm (median 115.9 µg/L) than in those who did not (median 62.2 µg/L; P < .001). This difference persisted when 31 spontaneous preterm births and 21 indicated preterm births were analyzed separately. The odds ratios for preterm birth in the highest TAT quartile relative to the lowest quartile was 4.98 (95% confidence interval, 1.17-22.01; P = .007)., Conclusion: We found a difference in the pattern of intraamniotic thrombin generation between women destined to deliver at term and those who deliver preterm, regardless of the type of preterm birth., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: The purpose of this study was to determine outcomes, after the use of propensity score techniques, to create balanced groups according to whether a woman undergoes elective repeat cesarean delivery (ERCD) or trial of labor (TOL)., Study Design: Women who were eligible for a TOL with 1 previous low transverse incision were categorized according to whether they underwent an ERCD or TOL. A propensity score technique was used to develop ERCD and TOL groups with comparable baseline characteristics. Outcomes were assessed with conditional logistic regression., Results: The rates of endometritis, operative injury, respiratory distress syndrome, and newborn infant infection were lower and the rates of hysterectomy and wound complication were higher in the ERCD group., Conclusion: Propensity score techniques can be used to generate comparable ERCD and TOL groups. Some types of maternal morbidity (such as hysterectomy) are higher; other types (such as operative injury) are lower in the ERCD group. Although the absolute risk is low, neonatal morbidity appears to be lower in the ERCD group., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: The objective of the study was to compare pregnancy outcomes by completed week of gestation after 39 weeks with outcomes at 39 weeks., Study Design: Secondary analysis of a multicenter trial of fetal pulse oximetry in spontaneously laboring or induced nulliparous women at a gestation of 36 weeks or longer. Maternal outcomes included a composite (treated uterine atony, blood transfusion, and peripartum infections) and cesarean delivery. Neonatal outcomes included a composite of death, neonatal respiratory and other morbidities, and neonatal intensive care unit admission., Results: Among the 4086 women studied, the risks of the composite maternal outcome (P value for trend < .001), cesarean delivery (P < .001), and composite neonatal outcome (P = .047) increased with increasing gestational age from 39 to 41 or more completed weeks. Adjusted odds ratios (95% confidence interval) for 40 and 41 or more weeks, respectively, compared with 39 weeks were 1.29 (1.03-1.64) and 2.05 (1.60-2.64) for composite maternal outcome, 1.28 (1.05-1.57) and 1.75 (1.41-2.16) for cesarean delivery, and 1.25 (0.86-1.83) and 1.37 (0.90-2.09) for composite neonatal outcome., Conclusion: Risks of maternal morbidity and cesarean delivery but not neonatal morbidity increased significantly beyond 39 weeks., (Copyright © 2012 Mosby, Inc. All rights reserved.)

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., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: We sought to evaluate the interaction between repeated-course antenatal corticosteroids and inflammation gene polymorphisms with neurodevelopmental outcomes at age 2 years., Study Design: We conducted nested case-control analysis of a randomized controlled trial of single- vs repeated-course antenatal corticosteroids. Cases had mental and/or psychomotor delay at age 2 years. Controls had normal neurodevelopment. Previous analyses of 125 cases and 147 controls identified 4 inflammation gene polymorphisms associated with neurodevelopmental delay at age 2 years., Results: The interaction between repeated-course corticosteroids and the interleukin (IL)-6 -174 genotype with neurodevelopmental delay was significant (P = .046). The IL-6 -174 GG genotype was associated with neurodevelopmental delay at age 2 years in the single-course corticosteroid group (odds ratio, 6.47; 95% confidence interval, 1.86-22.50). Exposure to repeated-course antenatal corticosteroids abrogated this genotype effect (odds ratio, 1.30; 95% confidence interval, 0.48-3.54). Results were unchanged after controlling for potential confounders., Conclusion: Repeated-course antenatal steroids may reduce the increased risk of neurodevelopmental delay at age 2 years associated with IL-6 -174 GG genotype., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: To compare endothelial nitric oxide synthase expression and capillary density (CDS) in placentas exposed to single or multiple courses of betamethasone., Study Design: Placental specimens exposed to single vs repeat courses of betamethasone were analyzed through immunohistochemistry and digital image quantification for endothelial nitric oxide synthase and CD34. Quantified endothelial nitric oxide synthase staining, calculated capillary density, ratio of endothelial nitric oxide synthase to capillary density, and clinical characteristics were compared. Linear regression was performed with these as dependent variables., Results: Mean and maximum capillary density were increased (P = .013 and .005) and the ratio of endothelial nitric oxide synthase to capillary density decreased (P = .016) in specimens exposed to 4 courses of betamethasone compared with 1 to 3 courses. Exposure to 4 courses of betamethasone was associated with increased capillary density, but not with endothelial nitric oxide synthase expression., Conclusion: Exposure to 4 courses of betamethasone is associated with increased placental capillary density. The placental effects of multiple courses of betamethasone are unrelated to endothelial nitric oxide synthase expression., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: The objective of the study was to examine whether the size of silicon nanovectors (SNVs) inhibits their entrance into the fetal circulation., Study Design: Pregnant rats were intravenously administered with SNVs or saline. The SNVs were spherical particles with 3 escalating diameters: 519 nm, 834 nm, and 1000 nm. The maternal and fetal distribution of SNVs was assessed., Results: In animals that received 1000 or 834 nm SNV, silicon (Si) levels were significantly higher in the maternal organs vs the saline group, whereas the silicon levels in fetal tissues were similar to controls. However, in animals receiving 519 nm SNVs, fetal silicon levels were significantly higher in the SNV group compared with the saline group (5.93 ± 0.67 μg Si per organ vs 4.80 ± 0.33, P = .01)., Conclusion: Larger SNVs do not cross the placenta to the fetus and, remaining within the maternal circulation, can serve as carriers for harmful medications in order to prevent fetal exposure., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: The purpose of this study was to determine whether mid-trimester insulin resistance is associated with subsequent preeclampsia., Study Design: This was a secondary analysis of 10,154 nulliparous women who received vitamin C and E or placebo daily from 9-16 weeks gestation until delivery. Of these, 1187 women had fasting plasma glucose and insulin tested between 22 and 26 weeks gestation. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index., Results: Obese women were twice as likely to have a HOMA-IR result of ≥75th percentile. Hispanic and African American women had a higher percentage at ≥75th percentile for HOMA-IR than white women (42.2%, 27.2%, and 16.9%, respectively; P < .001). A HOMA-IR result of ≥75th percentile was higher among the 85 nulliparous women who subsequently had preeclampsia, compared with women who remained normotensive (40.5% vs 24.8%; adjusted odds ratio, 1.9; 95% confidence interval, 1.1-3.2). Quantitative insulin sensitivity check index results were similar to the HOMA-IR results., Conclusion: Midtrimester maternal insulin resistance is associated with subsequent preeclampsia., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: The purpose of this study was to report the frequency of fetal growth restriction (FGR) based on indication for late preterm birth (LPTB)., Study Design: Singleton live born pregnancies that were delivered from 34-36 weeks 6 days of gestation over a 1-year period at a tertiary care medical center were studied. Indications for delivery were categorized as spontaneous (spontaneous preterm birth or premature rupture of membranes), medically indicated, or elective. A customized birthweight percentile was calculated for each pregnancy; the rate of FGR was compared based on indication for LPTB., Results: There were 482 LPTBs that met all criteria. Customized birthweight percentiles (median; interquartile range) were different among groups (spontaneous, 45.5%; 20.8-73.5%; medically indicated, 26.9%; 4.1-63.6%; elective, 45.9%; 22.2-78.3%; P = .001). The rate of FGR was also different among groups (spontaneous, 13%; medically indicated, 32%; elective, 21%; P = .001)., Conclusion: With the use of customized birthweight standards, we found that FGR complicated approximately one-third of all cases of medically indicated LPTB., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: Antenatal corticosteroids (ACS) decrease respiratory distress syndrome in singleton gestations. Twin data are less clear. Obesity and body mass index (BMI) also affect medication distribution volume. We evaluated whether maternal or neonatal cord betamethasone concentrations differed in twin gestations or obese patients., Study Design: Participants receiving betamethasone in a randomized controlled trial of weekly ACS were identified. We analyzed maternal delivery and cord serum betamethasone concentrations comparing singletons with twins and obese (BMI > or =30 kg/m(2)) with nonobese women., Results: Fifty-five maternal and 45 cord blood samples were available. Unadjusted median maternal serum concentrations appeared paradoxically higher in both twin gestations and the obese. However, after controlling for confounders, there were no differences in betamethasone concentrations in maternal serum or cord blood between singletons and twins (P = .61 vs P = .14) or nonobese and obese women (P = .67 vs .12)., Conclusion: Maternal and umbilical cord blood serum betamethasone concentrations are not different in twin gestations or obese women., (Copyright 2010 Mosby, Inc. All rights reserved.)

Objective: The purpose of this study was to evaluate the association between fetal inflammation and coagulation gene single-nucleotide polymorphisms (SNPs) and neurodevelopmental delay at age 2 years., Study Design: We conducted a case-controlled secondary analysis of a randomized trial of single- vs multiple-course corticosteroids. Multiplex assay assessed 46 SNPs. Cases had mental developmental and/or psychomotor delay at age 2 years. Control subjects had normal neurodevelopment., Results: One hundred twenty-five cases and 147 control subjects were analyzed. Allele frequencies were different between cases and control subjects for interleukin (IL)1beta-511 (P = .009), IL4R-148 (P = .03), IL6-174 (P = .02), and IL6-176 (P = .007). Genotype frequencies were different for IL1beta-511 (P = .03) and IL6-174 (P = .04). Results for IL1beta-511, IL4R-148, and IL6-176 remained significant after logistic regression analysis. IL1beta-511 and IL6-176 minor alleles were associated with increased risk of neurodevelopmental delay (odds ratio, 3.1; 95% confidence interval [CI], 1.2-8.2 and 2.2; 95% CI, 1.2-3.9, respectively). IL4R-148 minor allele was protective (odds ratio, 0.6; 95% CI, 0.4-0.9)., Conclusion: Fetal SNPs in IL1beta, IL-4R, and IL-6 may be associated with neurodevelopmental delay at age 2 years., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Objective: The aim of this study was to determine the effect of maternal body mass index on the incidence of neonatal prematurity morbidities in those who receive corticosteroids., Study Design: This was a secondary analysis of a trial of corticosteroids in women at risk for preterm birth. Women receiving a single course of corticosteroids were classified by their prepregnancy body mass index (<25 and > or = 25) and compared on a composite outcome comprised of several neonatal morbidities and on each individual outcome., Results: Of 183 eligible women, 96 (52.5%) had a body mass index of <25 and 87 (47.5%) had a body mass index of > or = 25. The composite outcome occurred more frequently in the body mass index of > or = 2 5 group (28.7%), compared with those with a body mass index of <25 (18.8%), although this was not statistically significant (odds ratio, 1.75; 95% confidence interval, 0.83-3.72). Body mass index was not associated with outcomes after adjusting for confounding., Conclusion: Maternal body mass index did not affect neonatal prematurity morbidities in those receiving corticosteroids., (Copyright 2010 Mosby, Inc. All rights reserved.)

Objective: Our objective was to describe indications for late preterm birth (LPTB) and estimate the frequency of potentially avoidable LPTB deliveries., Study Design: Singleton pregnancies delivered between 34(0/7)-36(6/7) weeks over a 1-year period at a tertiary care medical center were studied. Indications for delivery were categorized as spontaneous (spontaneous preterm birth or premature rupture of membranes) or iatrogenic (elective or medically indicated). Potentially avoidable deliveries were defined as those with elective or medical stable, but high-risk indications., Results: During the study period there were 514 LPTB (spontaneous preterm birth 36.2%, preterm premature rupture of membranes 17.7%, medically indicated 37.9%, and elective 8.2%). Potentially avoidable LPTB accounted for 17% of LPTB and were associated with later gestational age (odds ratio [OR], 4.7; 95% confidence interval [CI], 2.5-8.6), nonfaculty physician status (OR, 2.8; 95% CI, 1.5-5.1), and prior cesarean delivery (OR, 1.5; 95% CI, 1.0-2.1)., Conclusion: At our institution, <10% of LPTB are purely elective and >80% are clearly unavoidable.

Objective: The purpose of this study was to assess maternal and perinatal outcomes as a function of second-stage labor duration., Study Design: We assessed outcomes in nulliparous laboring women who were enrolled in a trial of fetal pulse oximetry., Results: Of 5341 participants, 4126 women reached the second stage of labor. As the duration of the second stage increased, spontaneous vaginal delivery rates declined, from 85% when the duration was <1 hour to 9% when it was > or =5 hours. Adverse maternal outcomes that were associated significantly with the duration of the second stage of labor included chorioamnionitis (overall rate, 3.9%), third- or fourth-degree perineal laceration (overall rate, 8.7%), and uterine atony (overall rate, 3.9%). Odds ratios for each additional hour of the second stage of labor ranged from 1.3-1.8. Among individual adverse neonatal outcomes, only admission to a neonatal intensive care unit was associated significantly with second stage duration (odds ratio, 1.4)., Conclusion: The second stage of labor does not need to be terminated for duration alone.

Objective: To compare the rates of gestational diabetes among women who received serial doses of 17-alpha hydroxyprogesterone caproate vs placebo., Study Design: Secondary analysis of 2 double-blind randomized placebo-controlled trials of 17-alpha hydroxyprogesterone caproate given to women at risk for preterm delivery. The incidence of gestational diabetes was compared between women who received 17-alpha hydroxyprogesterone caproate or placebo., Results: We included 1094 women; 441 had singleton and 653 had twin gestations. Combining the 2 studies, 616 received 17-alpha hydroxyprogesterone caproate and 478 received placebo. Among singleton and twin pregnancies, rates of gestational diabetes were similar in women receiving 17-alpha hydroxyprogesterone caproate vs placebo (5.8% vs 4.7%; P = .64 and 7.4% vs 7.6%; P = .94, respectively). In the multivariable model, progesterone was not associated with gestational diabetes (adjusted odds ratio, 1.04; 95% confidence interval, 0.62-1.73)., Conclusion: Weekly administration of 17-alpha hydroxyprogesterone caproate is not associated with higher rates of gestational diabetes in either singleton or twin pregnancies.

Objective: The objective of the study was to assess cerclage to prevent recurrent preterm birth in women with short cervix., Study Design: Women with prior spontaneous preterm birth less than 34 weeks were screened for short cervix and randomly assigned to cerclage if cervical length was less than 25 mm., Results: Of 1014 women screened, 302 were randomized; 42% of women not assigned and 32% of those assigned to cerclage delivered less than 35 weeks (P = .09). In planned analyses, birth less than 24 weeks (P = .03) and perinatal mortality (P = .046) were less frequent in the cerclage group. There was a significant interaction between cervical length and cerclage. Birth less than 35 weeks (P = .006) was reduced in the less than 15 mm stratum with a null effect in the 15-24 mm stratum., Conclusion: In women with a prior spontaneous preterm birth less than 34 weeks and cervical length less than 25 mm, cerclage reduced previable birth and perinatal mortality but did not prevent birth less than 35 weeks, unless cervical length was less than 15 mm.

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 compare the vaginal delivery rate in women who undergo labor induction with preinduction misoprostol or oxytocin alone., Study Design: Women with singleton pregnancies and Bishop scores <5 with labor induction at > or = 24 weeks of gestation were eligible; they were assigned randomly to oxytocin alone or preinduction cervical ripening with misoprostol. Labor characteristics, maternal complications, and neonatal outcomes were analyzed., Results: One hundred sixty-three women received oxytocin, and 164 women received misoprostol. Maternal demographics, pretreatment Bishop scores, and labor analgesia were similar between groups. Vaginal delivery rates were also similar: 87% (n = 141) for oxytocin and 81% (n = 133) for misoprostol. Mean time from treatment to delivery was shorter for the oxytocin group, compared with the misoprostol group (13.1 vs 16.3 hours; P = .005). There was no difference in maternal complications or neonatal outcomes between groups., Conclusion: Preinduction cervical ripening with misoprostol did not improve the vaginal delivery rate and resulted in longer intervals to active labor and delivery. Preinduction cervical ripening with misoprostol may not be necessary.

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 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 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: 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 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 investigate dexamethasone redosing as function of time and dose., Study Design: We studied the effect of 48 hours' exposure to various concentrations of dexamethasone in a human pulmonary adenocarcinoma cell line (H-441). We measured the level of surfactant protein B (SP-B) mRNA by quantitative reverse transcription-PCR after initial dexamethasone exposure, and after redosing, 1 or 2 weeks later. Values are mean +/- SE for 5 experiments. Comparisons were made by Mann-Whitney and Kruskal-Wallis test with significance set at P < .05., Results: Induction of SP-B mRNA was maximal within 48 hours of the initial dexamethasone exposure. Redosing with the same dexamethasone concentration resulted in levels more than double those initially observed. Redosing with dexamethasone concentration 10 times lower had an effect comparable to that of the initial, higher concentration., Conclusion: Our results suggest a residual effect of the initial exposure that potentiates redosing, allowing significant dose reductions.

Objective: The purpose of this study was to compare the effect of a single 48-hour exposure to betamethasone or dexamethasone in the NCI-H441 cell line and in human type II pneumocytes., Study Design: NCI-H441 cells were exposed 48 hours to varying concentrations of betamethasone or dexamethasone (10(-10) to 10(-7) mol/L) alone or in combination with 1 mmol/L dibutyryl cyclic adenosine monophosphate. Likewise, human type II pneumocytes were exposed 48 hours to varying concentrations of betamethasone or dexamethasone (10(-9) to 10(-7) mol/L) alone or in combination with 1 mmol/L dibutyryl cyclic adenosine monophosphate. The measured outcome was the stimulatory effect on surfactant protein B gene transcription as expressed by surfactant protein B messenger RNA accumulation. The experiment was conducted 5 times in NCI-H441 cells and 6 times in type II cells, in parallel with control. Surfactant protein B messenger RNA was determined at control level and 48 hours after exposure by quantitative reverse transcription-polymerase chain reaction., Results: A similar dose-dependent response in surfactant protein B messenger RNA expression was seen with both betamethasone and dexamethasone. In human type II pneumocytes, the inductive profile of surfactant protein B messenger RNA after 48-hour exposure to betamethasone or dexamethasone was similar to that seen in the NCI-H441 cells., Conclusion: Dexamethasone and betamethasone achieved similar dose-response patterns of surfactant protein-B expression in vitro.