A Randomized Trial of the Effects of Ambient Operating Room Temperature on Neonatal Morbidity.

OBJECTIVE: Newborn hypothermia has been implicated in neonatal morbidity without randomized evidence that it compromises the infant. Our objective was to determine if a difference in operating room temperature at cesarean birth impacts neonatal morbidity. STUDY DESIGN: Women undergoing cesarean delivery of a liveborn infant without major malformations were included. The institutional preexisting operating room temperature of 20°C (67°F) was compared with an experimental group of 24°C (75°F) by cluster randomization assigned on a weekly basis. Newborn hypothermia was defined as axillary temperature on arrival to the nursery of less than 36.5°C (<97.7°F). The primary outcome was a composite of neonatal morbidity including respiratory support, sepsis, hypoglycemia, and neonatal death. RESULTS: Between November 2016 and May 2018, 5,221 women had cesarean deliveries at Parkland Hospital with 2,817 randomized to the standard care group and 2,404 to the experimental group. The rate of neonatal composite morbidity did not differ between the groups: standard care 398 (14%) versus experimental 378 (16%), p = 0.11. This was despite a significant decrease in the rate of neonatal hypothermia: standard care 1,195 (43%) versus experimental 414 (18%), p < 0.001. There was no difference in the composite outcome for preterm infants (<37 wk) between the groups: standard care 194 (49%) versus experimental 185 (54%), p = 0.25. CONCLUSION: An 8°F increase in operating room temperature was significantly associated with a reduced rate of neonatal hypothermia, although this decrease was not associated with a significant improvement in neonatal morbidity. However, the increase in operating room temperature was met with resistance from obstetricians and operating room personnel. This trial is registered (registration no.: NCT03008577).

Prediction of Cerebral Palsy or Death among Preterm Infants Who Survive the Neonatal Period.

OBJECTIVE: To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death. STUDY DESIGN: This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes (n = 11) and demographic and clinical factors (n = 10) evident by the time of discharge among surviving infants (n = 1889) and the primary outcome of death or moderate/severe CP at age 2 (n = 73) was estimated, and a prediction model was created. RESULTS: Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67-0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1-13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6-104.6), and male gender (OR: 2.5, CI: 1.4-4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78-0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants. CONCLUSION: IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae. KEY POINTS: · Factors known at hospital discharge are identified which are independently associated with death or CP by age 2.. · A model was created and validated using these findings to counsel parents.. · The risk of death or CP can be calculated at the time of hospital discharge..

A chronicle of the 17-alpha hydroxyprogesterone caproate story to prevent recurrent preterm birth.

Preterm birth is a substantial public health concern. In 2019, the US preterm birth rate was 10.23%, which is the fifth straight year of increase in this rate. Moreover, preterm birth accounts for approximately 1 in 6 infant deaths, and surviving children often suffer developmental delay or long-term neurologic impairment. Although the burden of preterm birth is clear, identifying strategies to reduce preterm birth has been challenging. On October 29, 2019, a US Food and Drug Administration advisory committee voted 9 vs 7 to withdraw interim accelerated approval of 17-alpha hydroxyprogesterone caproate for preventing recurrent preterm birth because the called for a confirmatory trial, known as the Prevention of Preterm Birth in Women With a Previous Singleton Spontaneous Preterm Delivery trial, was not confirmatory. The Prevention of Preterm Birth in Women With a Previous Singleton Spontaneous Preterm Delivery trial included subjects enrolled in the United States and Canada to ensure that at least 10% of patients would be from North America; however, this trial took 9 years to complete and did not demonstrate significant treatment effects in the 2 primary outcomes of interest. Delivery before 35 weeks' gestation occurred in 122 of 1130 women (11%) given 17-alpha hydroxyprogesterone caproate compared with 66 of 578 women (11.5%) given placebo (relative risk, 0.95; 95% confidence interval, 0.71-1.26; P=.72). Similarly, the coprimary outcome neonatal composite index occurred in 61 of 1093 women (5.6%) given 17-alpha hydroxyprogesterone caproate compared with 28 of 559 women (5.0%) given placebo (relative risk, 1.12; 95% confidence interval, 0.68-1.61; P=.73). There was also a lack of efficacy for 17-alpha hydroxyprogesterone caproate treatment in the analysis of a variety of secondary outcomes. Like the Maternal-Fetal Medicine Units Network trial, the Prevention of Preterm Birth in Women With a Previous Singleton Spontaneous Preterm Delivery trial was also flawed. Importantly, the Maternal-Fetal Medicine Unit Network trial was the sole justification for treating women in the United States with 17-alpha hydroxyprogesterone caproate for nearly 2 decades. Currently, despite more than half a century, 17-alpha hydroxyprogesterone caproate still has not been found to be clearly effective. In this context, how does the advising physician dependent on scientific evidence advise a patient that 17-alpha hydroxyprogesterone caproate is effective when the evidence to support this advice has repeatedly been found to be inadequate? This clinical opinion is a critical appraisal of the 2 randomized trials examining the efficacy of 17-alpha hydroxyprogesterone caproate to prevent recurrent preterm birth and a chronicle of events in the regulatory process of drug approval to help answer this question. With this examination, these events illustrate the complexity of pharmaceutical regulations in the era of accelerated Food and Drug Administration approval and characterize the financial impact and influence in medicine. In this report, we also emphasize the value of observational studies in contemporary practice and identify other examples in medicine where accelerated Food and Drug Administration approval has been withdrawn. Importantly, the themes of the 17-alpha hydroxyprogesterone caproate story are not limited to obstetrics. It can also serve as a microcosm of issues within the US healthcare system, which ultimately contributes to the high cost of healthcare. In our opinion, the answer to the question is clear-the facts speak for themselves-and we believe 17-alpha hydroxyprogesterone caproate should not be endorsed for use to prevent recurrent preterm birth in the United States.

Episiotomy: Evolution of a Common Obstetric Practice at a Public Hospital.

OBJECTIVE: This study aimed to evaluate the rate and impact of episiotomy on maternal and newborn outcomes before and after restricted use of episiotomy. STUDY DESIGN: This population-based observational study used an obstetric database of all deliveries since 1990 that has been maintained with quality checks. Inclusion criteria were vaginal deliveries at ≥37 weeks. Exclusion criteria included fetal malformations, multifetal gestations, or fetal deaths known on arrival to Labor and Delivery. The primary outcomes of interest were episiotomy, perineal lacerations, and newborn outcomes. To evaluate the impact of restrictive episiotomy, data from 1990 to 1997 (35% overall episiotomy rate) were compared with data from 2010 to 2017 (2.5% overall episiotomy rate). Univariable analysis of maternal and infant outcomes were performed comparing the two-time epochs with the Pearson's Chi-squared test. RESULTS: Overall, 268,415 women met inclusion criteria and 49,089 (18.2%) had an episiotomy. The rate of episiotomy decreased from 37% of deliveries in 1990 to 2% in 2017. A total of 82,082 deliveries occurred in the 1990 to 1997 epoch and 57,183 in 2010 to 2017. Indicated use of episiotomy was associated with a significant decrease in third and fourth degree lacerations. Immediate newborn condition (5-minute Apgar's score ≤3 and umbilical artery pH <7.1) and neonatal outcomes (intraventricular hemorrhage [IVH] grade 3/4, positive culture sepsis, neonatal seizures, and neonatal demise) were not significantly different. CONCLUSION: Selective, indicated use of episiotomy compared with routine was associated with lower rates of third/fourth-degree lacerations with no change in neonatal outcomes. The common obstetric practice of routinely performing episiotomy, presumably to prevent perineal trauma, proved untrue when analyzed over almost three decades. KEY POINTS: · Episiotomy use decreased overtime at our institution.. · Decreased episiotomy use was associated with significant improvement in maternal outcomes.. · Neonatal outcomes were unchanged suggesting no deleterious effects with restricted episiotomy..

Second-stage labor: consensus versus science.

There has been a recent significant evolution in suggested practices for the management of labor because of the increased national cesarean delivery rate. One of the most significant changes was promulgated by the 2014 Obstetric Care Consensus entitled, "Safe Prevention of Primary Cesarean Delivery," which recommended reconsideration of the upper limits of the length of labor in the second stage as well as the first stage. We previously published a 2016 Clinical Opinion challenging the second-stage practice change. Over the past 2 years, there have been at least 5 reports as well as 2 national organization statements supporting revised management of second-stage labor. We now revisit the second-stage issue because we believe that it is important to carefully clarify the current status resulting from consensus statements as well as the evolving current status of scientific evidence. We structured this Clinical Opinion using questions in an effort to chronicle the story of how obstetric precepts on second-stage labor in use for more than 50 years were being replaced. How did we get here? What is the current evidence? What can be learned from this experience? Should American obstetrics now "fall back" to pre-existing obstetric precepts for the management of second-stage labor after having "sprung forward" an additional hour-namely, lengthening the duration of acceptable second-stage labor to 4 hours as recommended by the Obstetric Care Consensus? We believe that the data published since our 2016 Clinical Opinion buttress our original position that prolongation of the second stage beyond historical precepts is unsafe.

"New or not-so-new" labor management practices and cesarean delivery for arrest of progress.

BACKGROUND: Because nearly one-third of births in the United States are now achieved by cesarean delivery, comprising more than 1.27 million women each year, national organizations have recently published revised guidelines for the management of labor. These new guidelines stipulate that labor arrest should not be diagnosed unless ≥6 cm cervical dilatation has been reached or labor has been stimulated for at ≥6 hours. OBJECTIVE: To determine the cervical dilatation and hours of labor stimulation prior to cesarean delivery for arrest of dilatation. MATERIALS AND METHODS: Between January 1, 1999, andDecember 31, 2000, a prospective observational study of all primary cesarean deliveries was conducted at 13 university centers comprising the Eunice Kennedy Shriver National Institute for Child Health and Human Development, Maternal-Fetal Medicine Units Network. This secondary analysis includes all live-born, singleton, nonanomalous, cephalic gestations delivered by primary cesarean delivery at ≥37 weeks. A cesarean delivery was considered to have been performed for arrest of dilatation if the indication for the procedure was failure to progress, cephalopelvic disproportion, or failed induction. Augmentation was defined as stimulation after spontaneous labor had been previously diagnosed. Analysis included both the latent and active phases of labor. The active phase of labor was diagnosed when cervical dilatation was ≥4 cm in the presence of uterine contractions. RESULTS: A total of 13,269 primary cesarean deliveries were available for analysis, 8,546 (65%) of which were performed for inadequate progress of labor with cervical dilatation recorded at the time of cesarean delivery. Of these cesarean deliveries for labor arrest, a total of 719 (8%) were performed in the latent phase of labor and 7827 (92%) were performed when cervical dilatation was ≥4 cm (active phase). Approximately two-thirds (n = =5876; 69%) received intrauterine pressure monitoring. A total of 5636 women (66% of those reaching the active phase of labor) had reached ≥6 cm cervical dilatation before cesarean delivery was performed. Moreover, 7440 (95%) of the 7827 women in active labor had ≥6 cm dilatation or had received labor stimulation ≥6 hours prior to cesarean delivery for arrest of dilatation. CONCLUSION: Women undergoing primary cesarean delivery for arrest of dilatation 15 years before the recommendations of the Obstetrics Care Consensus had received bona fide efforts to achieve adequate labor consistent with the recommendations of the Consensus. Because 95% of these women had ≥6 cm dilatation or had received labor stimulation ≥6 hours prior to cesarean delivery for arrest of dilatation, these new recommendations are unlikely to change the cesarean delivery rates.

Duration of Operative Vaginal Delivery and Adverse Obstetric Outcomes.

OBJECTIVE: This study aimed to evaluate whether the number of vacuum pop-offs, the number of forceps pulls, or the duration of operative vaginal delivery (OVD) is associated with adverse maternal and perinatal outcomes. STUDY DESIGN: This is a secondary analysis of a multicenter observational cohort of women who underwent an attempted OVD. Women were stratified by the duration of OVD and the number of pop-offs (vacuum) or pulls (forceps) attempted. Severe perineal lacerations, failed OVD, and a composite adverse neonatal outcome were compared by the duration of OVD and number of pop-offs or pulls. RESULTS: Of the 115,502 women in the primary cohort, 5,325 (4.6%) underwent an attempt at OVD: 3,594 (67.5%) with vacuum and 1,731 (32.5%) with forceps. After adjusting for potential confounders, an increasing number of pop-offs was associated with an increased odds of the composite adverse neonatal outcome. However, an increasing duration of vacuum exhibited a stronger association with the composite adverse neonatal outcome. Similarly, the number of forceps pulls was less strongly associated with the composite adverse neonatal outcome compared with the duration of forceps application. CONCLUSION: The duration of OVD may be more associated with adverse neonatal outcomes than the number of pop-offs or pulls.

Sex-Specific Genetic Susceptibility to Adverse Neurodevelopmental Outcome in Offspring of Pregnancies at Risk of Early Preterm Delivery.

OBJECTIVE: To evaluate sex-specific genetic susceptibility to adverse neurodevelopmental outcome (ANO, defined as cerebral palsy [CP], mental, or psychomotor delay) at risk for early preterm birth (EPTB, < 32 weeks). STUDY DESIGN: Secondary case-control analysis of a trial of magnesium sulfate (MgSO4) before anticipated EPTB for CP prevention. Cases are infants who died by the age of 1 year or developed ANO. Controls, matched by maternal race and infant sex, were neurodevelopmentally normal survivors. Neonatal DNA was evaluated for 80 polymorphisms in inflammation, coagulation, vasoregulation, excitotoxicity, and oxidative stress pathways using Taqman assays. The primary outcome for this analysis was sex-specific ANO susceptibility. Conditional logistic regression estimated each polymorphism's odds ratio (OR) by sex stratum, adjusting for gestational age, maternal education, and MgSO4-corticosteroid exposures. Holm-Bonferroni corrections, adjusting for multiple comparisons (p < 7.3 × 10-4), accounted for linkage disequilibrium between markers. RESULTS: Analysis included 211 cases (134 males; 77 females) and 213 controls (130 males; 83 females). An interleukin-6 (IL6) polymorphism (rs2069840) was associated with ANO in females (OR: 2.6, 95% confidence interval [CI]: 1.5-4.7; p = 0.001), but not in males (OR: 0.8, 95% CI: 0.5-1.2; p = 0.33). The sex-specific effect difference was significant (p = 7.0 × 10-4) and was unaffected by MgSO4 exposure. No other gene-sex associations were significant. CONCLUSION: An IL6 gene locus may confer susceptibility to ANO in females, but not males, after EPTB.

Risk of Ischemic Placental Disease in Relation to Family History of Preeclampsia.

OBJECTIVE: To assess the risk of ischemic placental disease (IPD) including preeclampsia, small for gestational age (SGA), and abruption, in relation to preeclampsia in maternal grandmother, mother, and sister(s). STUDY DESIGN: We performed a secondary analysis of data from a randomized trial of vitamins C and E for preeclampsia prevention. Data on family history of preeclampsia were based on recall by the proband. The associations between family history of preeclampsia and the odds of IPD were evaluated from alternating logistic regressions. RESULTS: Of the 9,686 women who delivered nonmalformed, singleton live births, 17.1% had IPD. Probands provided data on preeclampsia in 55.5% (n = 5,374) on all three family members, 26.5% (n = 2,562) in mother and sister(s) only, and 11.6% (n = 1,125) in sister(s) only. The pairwise odds ratio (pOR) of IPD was 1.16 (95% confidence interval [CI]: 1.00-1.36) if one or more of the female relatives had preeclampsia. The pORs of preeclampsia were 1.54 (95% CI: 1.12-2.13) and 1.35 (95% CI: 1.03-1.77) if the proband's mother or sister(s) had a preeclamptic pregnancy, respectively, but no associations were seen for SGA infant or abruption. CONCLUSION: This study suggests that IPD may share a predisposition with preeclampsia, suggesting a familial inheritance.

Defining failed induction of labor.

BACKGROUND: While there are well-accepted standards for the diagnosis of arrested active-phase labor, the definition of a "failed" induction of labor remains less certain. One approach to diagnosing a failed induction is based on the duration of the latent phase. However, a standard for the minimum duration that the latent phase of a labor induction should continue, absent acute maternal or fetal indications for cesarean delivery, remains lacking. OBJECTIVE: The objective of this study was to determine the frequency of adverse maternal and perinatal outcomes as a function of the duration of the latent phase among nulliparous women undergoing labor induction. STUDY DESIGN: This study is based on data from an obstetric cohort of women delivering at 25 US hospitals from 2008 through 2011. Nulliparous women who had a term singleton gestation in the cephalic presentation were eligible for this analysis if they underwent a labor induction. Consistent with prior studies, the latent phase was determined to begin once cervical ripening had ended, oxytocin was initiated, and rupture of membranes had occurred, and was determined to end once 5-cm dilation was achieved. The frequencies of cesarean delivery, as well as of adverse maternal (eg, postpartum hemorrhage, chorioamnionitis) and perinatal (eg, a composite frequency of seizures, sepsis, bone or nerve injury, encephalopathy, or death) outcomes, were compared as a function of the duration of the latent phase (analyzed with time both as a continuous measure and categorized in 3-hour increments). RESULTS: A total of 10,677 women were available for analysis. In the vast majority (96.4%) of women, the active phase had been reached by 15 hours. The longer the duration of a woman's latent phase, the greater her chance of ultimately undergoing a cesarean delivery (P < .001, for time both as a continuous and categorical independent variable), although >40% of women whose latent phase lasted ≥18 hours still had a vaginal delivery. Several maternal morbidities, such as postpartum hemorrhage (P < .001) and chorioamnionitis (P < .001), increased in frequency as the length of latent phase increased. Conversely, the frequencies of most adverse perinatal outcomes were statistically stable over time. CONCLUSION: The large majority of women undergoing labor induction will have entered the active phase by 15 hours after oxytocin has started and rupture of membranes has occurred. Maternal adverse outcomes become statistically more frequent with greater time in the latent phase, although the absolute increase in frequency is relatively small. These data suggest that cesarean delivery should not be undertaken during the latent phase prior to at least 15 hours after oxytocin and rupture of membranes have occurred. The decision to continue labor beyond this point should be individualized, and may take into account factors such as other evidence of labor progress.

Neonatal outcomes of elective early-term births after demonstrated fetal lung maturity.

BACKGROUND: Studies of early-term birth after demonstrated fetal lung maturity show that respiratory and other outcomes are worse with early-term birth (370-386 weeks) even after demonstrated fetal lung maturity when compared with full-term birth (390-406 weeks). However, these studies included medically indicated births and are therefore potentially limited by confounding by the indication for delivery. Thus, the increase in adverse outcomes might be due to the indication for early-term birth rather than the early-term birth itself. OBJECTIVE: We examined the prevalence and risks of adverse neonatal outcomes associated with early-term birth after confirmed fetal lung maturity as compared with full-term birth in the absence of indications for early delivery. STUDY DESIGN: This is a secondary analysis of an observational study of births to 115,502 women in 25 hospitals in the United States from 2008 through 2011. Singleton nonanomalous births at 37-40 weeks with no identifiable indication for delivery were included; early-term births after positive fetal lung maturity testing were compared with full-term births. The primary outcome was a composite of death, ventilator for ≥2 days, continuous positive airway pressure, proven sepsis, pneumonia or meningitis, treated hypoglycemia, hyperbilirubinemia (phototherapy), and 5-minute Apgar <7. Logistic regression and propensity score matching (both 1:1 and 1:2) were used. RESULTS: In all, 48,137 births met inclusion criteria; the prevalence of fetal lung maturity testing in the absence of medical or obstetric indications for early delivery was 0.52% (n = 249). There were 180 (0.37%) early-term births after confirmed pulmonary maturity and 47,957 full-term births. Women in the former group were more likely to be non-Hispanic white, smoke, have received antenatal steroids, have induction, and have a cesarean. Risks of the composite (16.1% vs 5.4%; adjusted odds ratio, 3.2; 95% confidence interval, 2.1-4.8 from logistic regression) were more frequent with elective early-term birth. Propensity scores matching confirmed the increased primary composite in elective early-term births: adjusted odds ratios, 4.3 (95% confidence interval, 1.8-10.5) for 1:1 and 3.5 (95% confidence interval, 1.8-6.5) for 1:2 matching. Among components of the primary outcome, CPAP use and hyperbilirubinemia requiring phototherapy were significantly increased. Transient tachypnea of the newborn, neonatal intensive care unit admission, and prolonged neonatal intensive care unit stay (>2 days) were also increased with early-term birth. CONCLUSION: Even with confirmed pulmonary maturity, early-term birth in the absence of medical or obstetric indications is associated with worse neonatal respiratory and hepatic outcomes compared with full-term birth, suggesting relative immaturity of these organ systems in early-term births.

Incidence of early-onset sepsis in infants born to women with clinical chorioamnionitis.

Objective To determine the frequency of sepsis and other adverse neonatal outcomes in women with a clinical diagnosis of chorioamnionitis. Methods We performed a secondary analysis of a multi-center placebo-controlled trial of vitamins C/E to prevent preeclampsia in low risk nulliparous women. Clinical chorioamnionitis was defined as either the "clinical diagnosis" of chorioamnionitis or antibiotic administration during labor because of an elevated temperature or uterine tenderness in the absence of another cause. Early-onset neonatal sepsis was categorized as "suspected" or "confirmed" based on a clinical diagnosis with negative or positive blood, urine or cerebral spinal fluid cultures, respectively, within 72 h of birth. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Results Data from 9391 mother-infant pairs were analyzed. The frequency of chorioamnionitis was 10.3%. Overall, 6.6% of the neonates were diagnosed with confirmed (0.2%) or suspected (6.4%) early-onset sepsis. Only 0.7% of infants born in the setting of chorioamnionitis had culture-proven early-onset sepsis versus 0.1% if chorioamnionitis was not present. Clinical chorioamnionitis was associated with both suspected [OR 4.01 (3.16-5.08)] and confirmed [OR 4.93 (1.65-14.74)] early-onset neonatal sepsis, a need for resuscitation within the first 30 min after birth [OR 2.10 (1.70-2.61)], respiratory distress [OR 3.14 (2.16-4.56)], 1 min Apgar score of ≤3 [OR 2.69 (2.01-3.60)] and 4-7 [OR 1.71 (1.43-2.04)] and 5 min Apgar score of 4-7 [OR 1.67 (1.17-2.37)] (vs. 8-10). Conclusion Clinical chorioamnionitis is common and is associated with neonatal morbidities. However, the vast majority of exposed infants (99.3%) do not have confirmed early-onset sepsis.

Adverse Maternal and Neonatal Outcomes in Indicated Compared with Spontaneous Preterm Birth in Healthy Nulliparas: A Secondary Analysis of a Randomized Trial.

OBJECTIVE: To compare the risks of adverse maternal and neonatal outcomes associated with spontaneous (SPTB) versus indicated preterm births (IPTB). METHODS: A secondary analysis of a multicenter trial of vitamin C and E supplementation in healthy low-risk nulliparous women. Outcomes were compared between women with SPTB (due to spontaneous membrane rupture or labor) and those with IPTB (due to medical or obstetric complications). A primary maternal composite outcome included: death, pulmonary edema, blood transfusion, adult respiratory distress syndrome (RDS), cerebrovascular accident, acute tubular necrosis, disseminated intravascular coagulopathy, or liver rupture. A neonatal composite outcome included: neonatal death, RDS, grades III or IV intraventricular hemorrhage (IVH), sepsis, necrotizing enterocolitis (NEC), or retinopathy of prematurity. RESULTS: Of 9,867 women, 10.4% (N = 1,038) were PTBs; 32.7% (n = 340) IPTBs and 67.3% (n = 698) SPTBs. Compared with SPTB, the composite maternal outcome was more frequent in IPTB-4.4% versus 0.9% (adjusted odds ratio [aOR], 4.0; 95% confidence interval [CI], 1.4-11.8), as were blood transfusion and prolonged hospital stay (3.2 and 3.7 times, respectively). The frequency of composite neonatal outcome was higher in IPTBs (aOR, 1.8; 95% CI, 1.1-3.0), as were RDS (1.7 times), small for gestational age (SGA) < 5th percentile (7.9 times), and neonatal intensive care unit (NICU) admission (1.8 times). CONCLUSION: Adverse maternal and neonatal outcomes were significantly more likely with IPTB than with SPTB.

17-alpha Hydroxyprogesterone caproate did not reduce the rate of recurrent preterm birth in a prospective cohort study.

BACKGROUND: 17-alpha Hydroxyprogesterone caproate for prevention of recurrent preterm birth is recommended for use in the United States. OBJECTIVE: We sought to assess the clinical effectiveness of 17-alpha hydroxyprogesterone caproate to prevent recurrent preterm birth ≤35 weeks compared to similar births in our obstetric population prior to the implementation of 17-alpha hydroxyprogesterone caproate. STUDY DESIGN: This was a prospective cohort study of 17-alpha hydroxyprogesterone caproate in our obstetric population. The primary outcome was the recurrence of birth ≤35 weeks for the entire study cohort compared to a historical referent rate of 16.8% of recurrent preterm birth in our population. There were 3 secondary outcomes. First, did 17-alpha hydroxyprogesterone caproate modify a woman's history of preterm birth when taking into account her prior number and sequence of preterm and term births? Second, was recurrence of preterm birth related to 17-alpha hydroxyprogesterone caproate plasma concentration? Third, was duration of pregnancy modified by 17-alpha hydroxyprogesterone caproate treatment compared to a prior preterm birth? RESULTS: From January 2012 through March 2016, 430 consecutive women with prior births ≤35 weeks were treated with 17-alpha hydroxyprogesterone caproate. Nearly two thirds of the women (N = 267) began injections ≤18 weeks and 394 (92%) received a scheduled weekly injection within 10 days of reaching 35 weeks or delivery. The overall rate of recurrent preterm birth was 25% (N = 106) for the entire cohort compared to the 16.8% expected rate (P = 1.0). The 3 secondary outcomes were also negative. First, 17-alpha hydroxyprogesterone caproate did not significantly reduce the rates of recurrence regardless of prior preterm birth number or sequence. Second, plasma concentrations of 17-alpha hydroxyprogesterone caproate were not different (P = .17 at 24 weeks; P = .38 at 32 weeks) between women delivered ≤35 weeks and those delivered later in pregnancy. Third, the mean (±SD) interval in weeks of recurrent preterm birth before 17-alpha hydroxyprogesterone caproate use was 0.4 ± 5.3 weeks and the interval of recurrent preterm birth after 17-alpha hydroxyprogesterone caproate treatment was 0.1 ± 4.7 weeks (P = .63). A side effect of weekly 17-alpha hydroxyprogesterone caproate injections was an increase in gestational diabetes. Specifically, the rate of gestational diabetes was 13.4% in 17-alpha hydroxyprogesterone caproate-treated women compared to 8% in case-matched controls (P = .001). CONCLUSION: 17-alpha Hydroxyprogesterone caproate was ineffective for prevention of recurrent preterm birth and was associated with an increased rate of gestational diabetes.

Cell-Free Total and Fetal DNA in First Trimester Maternal Serum and Subsequent Development of Preeclampsia.

Objective The objective of this study was to assess the relationship between first trimester cell-free total and fetal DNA in maternal plasma and the subsequent development of preeclampsia. Study Design Nested case-control study of patients enrolled in the Combined Antioxidant and Preeclampsia Prediction Studies prediction study of 175 women who did and 175 women who did not develop preeclampsia. The predictive values of cell-free total and fetal DNA and the subsequent development of preeclampsia were measured using receiver operating characteristic curves. Results Cell-free total DNA was higher in African American (median; 25-75%; 6.15; 0.14-28.73; p = 0.02) and Hispanic (4.95; 0.20-26.82; p = 0.037) compared with white women (2.33; 0.03-13.10). Levels of cell-free total DNA were also associated with maternal body mass index (BMI) (p = 0.02). Cell-free total DNA levels were similar between women who later developed preeclampsia (3.52; 0.11-25.3) and controls (3.74; 0.12-21.14, p = 0.96). Conclusion There is no significant difference in levels of cell-free total DNA in the first trimester in women who subsequently develop preeclampsia. Levels of cell-free total DNA in the first trimester are increased in African American and Hispanic compared with white women, and levels increase with increasing BMI.

Second-stage labor: how long is too long?

The management of labor has come under increased scrutiny due to the rapid escalation of cesarean delivery in the United States. A workshop of the Society for Maternal-Fetal Medicine, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the American Congress of Obstetricians and Gynecologists was convened to address the rising cesarean delivery rates and one of their recommendations was that the accepted upper limit of the second stage of labor should be increased to ≥4 hours in nulliparous women with epidural analgesia and to ≥3 hours in parous women with epidural. This led to the inaugural Obstetric Care Consensus series document, "Safe Prevention of the Primary Cesarean Delivery," wherein the workshop recommendations on second-stage labor were promulgated nationally. The result is that the now acceptable maximum length of the second stage of labor exceeds the obstetric precepts that have been in use for >50 years. In this Clinical Opinion, we review the evidence on infant safety, vis-à-vis length of the second stage of labor. Our examination of the evidence begins at the outset of the 20th century and culminates in the very recent (2014) recommendation to abandon the long accepted obstetric paradigm that second-stage labor >3 hours in nulliparous women with labor epidural is unsafe for the unborn infant. We conclude that the currently available evidence fails to support the Obstetric Care Consensus position that longer second-stage labor is safe for the unborn infant. Indeed, the evidence suggests quite the opposite. We suggest that when infant safety is at stake the evidence should be robust before a new clinical road is taken. The evidence is not robust.

The impact of ambient operating room temperature on neonatal and maternal hypothermia and associated morbidities: a randomized controlled trial.

BACKGROUND: Neonatal hypothermia is common at the time of cesarean delivery and has been associated with a constellation of morbidities in addition to increased neonatal mortality. Additionally, maternal hypothermia is often uncomfortable for the surgical patient and has been associated with intraoperative and postoperative complications. Various methods to decrease the rates of neonatal and maternal hypothermia have been examined and found to have varying levels of success. OBJECTIVE: We sought to determine whether an increase in operating room temperature at cesarean delivery results in a decrease in the rate of neonatal hypothermia and associated morbidities. STUDY DESIGN: In this single-center randomized trial, operating room temperatures were adjusted weekly according to a cluster randomization schedule to either 20°C (67°F), which was the standard at our institution, or 23°C (73°F), which was the maximum temperature allowable per hospital policy. Neonatal hypothermia was defined as core body temperature <36.5°C (97.7°F) per World Health Organization criteria. The primary study outcome was neonatal hypothermia on arrival to the admitting nursery. Measures of neonatal morbidity potentially associated with hypothermia were examined. RESULTS: From February through July 2015, 791 women who underwent cesarean deliveries were enrolled, resulting in 410 infants in the 20°C standard management group and 399 in the 23°C study group. The rate of neonatal hypothermia on arrival to the admitting nursery was lower in the study group as compared to the standard management group: 35% vs 50%, P < .001. Moderate to severe hypothermia was infrequent when the operating room temperature was 23°C (5%); in contrast such hypothermia occurred in 19% of the standard management group, P < .001. Additionally, neonatal temperature in the operating room immediately following delivery and stabilization was also higher in the study group, 37.1 ± 0.6°C vs 36.9 ± 0.6°C, P < .001. We found no difference in rates of intubation, ventilator use, hypoglycemia, metabolic acidemia, or intraventricular hemorrhage. Fever (temperature >38.0°C or 100.4°F) on arrival to the admitting unit was uncommon and did not differ between the study groups. Maternal temperature on arrival to the operating room was not different between the 2 groups, however by delivery it was significantly lower in the standard management group, 36.2 ± 0.6°C vs 36.4 ± 0.6°C, P < .001. This effect persisted, as maternal temperature on arrival to the postoperative care area was lower in the standard management group, 36.1 ± 0.6°C vs 36.2 ± 0.6°C, P < .001, and the rate of hypothermia was higher, 77% vs 69%, P = .008. CONCLUSION: A modest increase in operating room temperature at the time of cesarean reduces the rate of neonatal and maternal hypothermia. We did not detect a decrease in neonatal morbidity, but the power to detect a small change in these outcomes was limited.

Prediction of Spontaneous Preterm Birth Among Nulliparous Women With a Short Cervix.

OBJECTIVES: The purpose of this study was to evaluate whether demographic and sonographic factors associated with spontaneous preterm birth among nulliparous women with a cervical length of less than 30 mm could be combined into an accurate prediction model for spontaneous preterm birth. METHODS: We conducted a secondary analysis of a trial of nulliparous women with a singleton gestation and a cervical length of less than 30 mm on transvaginal sonography between 16 and 22 weeks who lacked other risk factors for spontaneous (eg, prior cervical excisional procedure) or medically indicated (eg, chronic hypertension) preterm birth, who were randomized to either 17α-hydroxyprogesterone caproate treatment or a placebo. Risk factors associated with spontaneous preterm birth within the entire cohort were identified by univariable analysis. Factors significantly associated (P < .05) with spontaneous preterm birth were included in a multivariable logistic regression analysis to determine whether an accurate prediction model could be developed. RESULTS: Of the 657 randomized patients, 109 (16.6%) had spontaneous preterm birth before 37 weeks' gestation. Logistic regression analysis revealed only cervical length (odds ratio, 1.06 per 1-mm decrease; 95% confidence interval, 1.02-1.10) to be associated with spontaneous preterm birth. The area under the receiver operating characteristic curve based on this regression was low (0.63; 95% confidence interval, 0.58-0.69). Results were similar for the outcome of spontaneous preterm birth before 34 weeks. CONCLUSIONS: An accurate prediction model for spontaneous preterm birth among nulliparous women with a short cervix could not be developed.

Waist-to-Hip Ratio versus Body Mass Index as Predictor of Obesity-Related Pregnancy Outcomes.

Objective In nonpregnant populations the waist-to-hip ratio (WHR) is a better predictor of obesity-related outcomes than body mass index (BMI). Our objective was to determine, in pregnancy, the relationship between these measures of obesity, and large-for-gestational age (LGA) and cesarean delivery (CD). Methods This is a secondary analysis of data from the Combined Antioxidant and Preeclampsia Prediction Study. Women with a WHR of ≥ 0.85 and 0.80 to 0.84 at 9 to 16 weeks gestation were compared with those with a WHR < 0.80. Women with early pregnancy BMI ≥ 30.0 kg/m(2) (obese) and 25.0 to 29.9 kg/m(2) (overweight) were compared with those < 25.0 kg/m(2). LGA was defined as > 90% by Alexander nomogram. Univariable analysis, logistic regression, and receiver operating characteristic curves were used. Results Data from 2,276 women were analyzed. After correcting for potential confounders, only BMI ≥ 30 was significantly associated with LGA (adjusted odds ratio [aOR]: 2.07, 1.35-3.16) while BMI 25.0-29.9 (aOR: 1.5, 0.98-2.28), WHR 0.8-0.84 (aOR: 1.33, 0.83-2.13), and WHR ≥ 0.85 (aOR: 1.05, 0.67-1.65) were not. Risk for CD was increased for women with elevated WHR and with higher BMI compared with normal. Conclusion WHR is not associated with LGA. While BMI performed better than WHR, neither was a strong predictor of LGA or need for CD in low-risk nulliparous women.

Relationship of Early Pregnancy Waist-to-Hip Ratio versus Body Mass Index with Gestational Diabetes Mellitus and Insulin Resistance.

OBJECTIVE: To determine the risk of gestational diabetes mellitus (GDM) and insulin resistance (IR) in obesity defined by body mass index (BMI), waist-to-hip ratio (WHR), or both combined. METHODS: Secondary analysis of a randomized multicenter trial of antioxidant supplementation versus placebo in nulliparous low-risk women to prevent pregnancy associated hypertension. Women between 9 and 16 weeks with data for WHR and BMI were analyzed for GDM (n = 2,300). Those with fasting glucose and insulin between 22 and 26 weeks (n = 717) were analyzed for IR by homeostatic model assessment of IR (normal, ≤ 75th percentile). WHR and BMI were categorized as normal (WHR, < 0.80; BMI, < 25 kg/m(2)); overweight (WHR, 0.8-0.84; BMI, 25-29.9 kg/m(2)); and obese (WHR, ≥ 0.85; BMI ≥ 30 kg/m(2)). Receiver operating characteristic curves and logistic regression models were used. RESULTS: Compared with normal, the risks of GDM or IR were higher in obese by BMI or WHR. The subgroup with obesity by WHR but not by BMI had no increased risk of GDM. BMI was a better predictor of IR (area under the curve [AUC]: 0.71 [BMI], 0.65 [WHR], p = 0.03) but similar to WHR for GDM (AUC: 0.68 [BMI], 0.63 [WHR], p = 0.18). CONCLUSION: Increased WHR and BMI in early pregnancy are associated with IR and GDM. BMI is a better predictor of IR compared with WHR. Adding WHR to BMI does not improve its ability to detect GDM or IR.