New labor curves of dilation and station to improve the accuracy of predicting labor progress.

BACKGROUND: The diagnosis of failure to progress, the most common indication for intrapartum cesarean delivery, is based on the assessment of cervical dilation and station over time. Labor curves serve as references for expected changes in dilation and fetal descent. The labor curves of Friedman, Zhang et al, and others are based on time alone and derived from mothers with spontaneous labor onset. However, labor induction is now common, and clinicians also consider other factors when assessing labor progress. Labor curves that consider the use of labor induction and other factors that influence labor progress have the potential to be more accurate and closer to clinical decision-making. OBJECTIVE: This study aimed to compare the prediction errors of labor curves based on a single factor (time) or multiple clinically relevant factors using two modeling methods: mixed-effects regression, a standard statistical method, and Gaussian processes, a machine learning method. STUDY DESIGN: This was a longitudinal cohort study of changes in dilation and station based on data from 8022 births in nulliparous women with a live, singleton, vertex-presenting fetus ≥35 weeks of gestation with a vaginal delivery. New labor curves of dilation and station were generated with 10-fold cross-validation. External validation was performed using a geographically independent group. Model variables included time from the first examination in the 20 hours before delivery; dilation, effacement, and station recorded at the previous examination; cumulative contraction counts; and use of epidural anesthesia and labor induction. To assess model accuracy, differences between each model's predicted value and its corresponding observed value were calculated. These prediction errors were summarized using mean absolute error and root mean squared error statistics. RESULTS: Dilation curves based on multiple parameters were more accurate than those derived from time alone. The mean absolute error of the multifactor methods was better (lower) than those of the single-factor methods (0.826 cm [95% confidence interval, 0.820-0.832] for the multifactor machine learning and 0.893 cm [95% confidence interval, 0.885-0.901] for the multifactor mixed-effects method and 2.122 cm [95% confidence interval, 2.108-2.136] for the single-factor methods; P<.0001 for both comparisons). The root mean squared errors of the multifactor methods were also better (lower) than those of the single-factor methods (1.126 cm [95% confidence interval, 1.118-1.133] for the machine learning [P<.0001] and 1.172 cm [95% confidence interval, 1.164-1.181] for the mixed-effects methods and 2.504 cm [95% confidence interval, 2.487-2.521] for the single-factor [P<.0001 for both comparisons]). The multifactor machine learning dilation models showed small but statistically significant improvements in accuracy compared to the mixed-effects regression models (P<.0001). The multifactor machine learning method produced a curve of descent with a mean absolute error of 0.512 cm (95% confidence interval, 0.509-0.515) and a root mean squared error of 0.660 cm (95% confidence interval, 0.655-0.666). External validation using independent data produced similar findings. CONCLUSION: Cervical dilation models based on multiple clinically relevant parameters showed improved (lower) prediction errors compared to models based on time alone. The mean prediction errors were reduced by more than 50%. A more accurate assessment of departure from expected dilation and station may help clinicians optimize intrapartum management.

Booster course of antenatal corticosteroids after preterm prelabor rupture of membranes: a double-blind randomized trial.

BACKGROUND: Preterm prelabor rupture of membranes is a leading cause of preterm birth and is responsible for 18% to 20% of perinatal deaths in the United States. An initial course of antenatal corticosteroids has been shown to reduce morbidity and mortality in patients with preterm prelabor rupture of membranes. For patients who remain undelivered for 7 days or more after the initial course of antenatal corticosteroids, it is uncertain whether a booster course of antenatal corticosteroids reduces neonatal morbidity or increases the infection risk. The American College of Obstetricians and Gynecologists has concluded that the current evidence is insufficient to make a recommendation. OBJECTIVE: This study aimed to evaluate if a single booster course of antenatal corticosteroids improves neonatal outcomes after preterm prelabor rupture of membranes. STUDY DESIGN: We conducted a multicenter, placebo-controlled randomized clinical trial. The inclusion criteria were preterm prelabor rupture of membranes, gestational age of 24.0 to 32.9 weeks, singleton, initial antenatal corticosteroid course administered at least 7 days before randomization, and planned expectant management. Consenting patients were randomized in gestational age blocks to either receive booster antenatal corticosteroids (12 mg betamethasone every 24 hours for 2 days) or a saline placebo. The primary outcome was composite neonatal morbidity or death. A sample size of 194 patients was calculated to yield 80% power at P<.05 to detect a reduction in primary outcome from 60% in placebo group to 40% in antenatal corticosteroids group. RESULTS: From April 2016 through August 2022, 194 patients consented and were randomized (47% of 411 eligible patients). Intent-to-treat analysis was performed on 192 patients (2 placebo patients left hospital, outcomes unknown). The groups had similar baseline characteristics. The primary outcome occurred in 64% of patients who received booster antenatal corticosteroids vs in 66% of patients who received the placebo (odds ratio, 0.82; 95% confidence interval, 0.43-1.57; gestational age-stratified Cochran-Mantel-Haenszel test). Individual components of the primary outcome and secondary neonatal and maternal outcomes were not significantly different between the antenatal corticosteroids and placebo groups. Specifically, chorioamnionitis (22% vs 20%), postpartum endometritis (1% vs 2%), wound infections (2% vs 0%), and proven neonatal sepsis (5% vs 3%) were not different between the groups. CONCLUSION: A booster course of antenatal corticosteroids at least 7 days after the first antenatal corticosteroids course in patients with preterm prelabor rupture of membranes did not improve neonatal morbidity or any other outcome in this adequately-powered, double-blind randomized clinical trial. Booster antenatal corticosteroids did not increase maternal or neonatal infection.

Should case management be considered a component of obstetrical interventions for pregnancies at risk of preterm birth?

Preterm birth remains the leading cause of morbidity and mortality among nonanomalous neonates in the United States. Unfortunately, preterm birth rates remain high despite current medical interventions such as progestogen supplementation and cerclage placement. Case management, which encompasses coordinated care aimed at providing a more comprehensive and supportive environment, is a key component in improving health and reducing costs in other areas of medicine. However, it has not made its way into the general lexicon and practice of obstetrical care. Case management intended for decreasing prematurity or ameliorating its consequences may include specialty clinics, social services, coordination of specialty services such as nutrition counseling, home visits or frequent phone calls by specially trained personnel, and other elements described herein. It is not currently included in nor is it advocated for as a recommended prematurity prevention approach in the American College of Obstetricians and Gynecologists or Society for Maternal-Fetal Medicine guidelines for medically indicated or spontaneous preterm birth prevention. Our review of existing evidence finds consistent reductions or trends toward reductions in preterm birth with case management, particularly among individuals with high a priori risk of preterm birth across systematic reviews, metaanalyses, and randomized controlled studies. These findings suggest that case management has substantial potential to improve the environmental, behavioral, social, and psychological factors with patients at risk of preterm birth.

Clinical and economic evaluation of a proteomic biomarker preterm birth risk predictor: cost-effectiveness modeling of prenatal interventions applied to predicted higher-risk pregnancies within a large and diverse cohort.

OBJECTIVES: Preterm birth occurs in more than 10% of U.S. births and is the leading cause of U.S. neonatal deaths, with estimated annual costs exceeding $25 billion USD. Using real-world data, we modeled the potential clinical and economic utility of a prematurity-reduction program comprising screening in a racially and ethnically diverse population with a validated proteomic biomarker risk predictor, followed by case management with or without pharmacological treatment. METHODS: The ACCORDANT microsimulation model used individual patient data from a prespecified, randomly selected sub-cohort (N = 847) of a multicenter, observational study of U.S. subjects receiving standard obstetric care with masked risk predictor assessment (TREETOP; NCT02787213). All subjects were included in three arms across 500 simulated trials: standard of care (SoC, control); risk predictor/case management comprising increased outreach, education and specialist care (RP-CM, active); and multimodal management (risk predictor/case management with pharmacological treatment) (RP-MM, active). In the active arms, only subjects stratified as higher risk by the predictor were modeled as receiving the intervention, whereas lower-risk subjects received standard care. Higher-risk subjects' gestational ages at birth were shifted based on published efficacies, and dependent outcomes, calibrated using national datasets, were changed accordingly. Subjects otherwise retained their original TREETOP outcomes. Arms were compared using survival analysis for neonatal and maternal hospital length of stay, bootstrap intervals for neonatal cost, and Fisher's exact test for neonatal morbidity/mortality (significance, p < .05). RESULTS: The model predicted improvements for all outcomes. RP-CM decreased neonatal and maternal hospital stay by 19% (p = .029) and 8.5% (p = .001), respectively; neonatal costs' point estimate by 16% (p = .098); and moderate-to-severe neonatal morbidity/mortality by 29% (p = .025). RP-MM strengthened observed reductions and significance. Point estimates of benefit did not differ by race/ethnicity. CONCLUSIONS: Modeled evaluation of a biomarker-based test-and-treat strategy in a diverse population predicts clinically and economically meaningful improvements in neonatal and maternal outcomes.

Preterm birth, defined as delivery before 37 weeks' gestation, is the leading cause of illness and death in newborns. In the United States, more than 10% of infants are born prematurely, and this rate is substantially higher in lower-income, inner-city and Black populations. Prematurity associates with greatly increased risk of short- and long-term medical complications and can generate significant costs throughout the lives of affected children. Annual U.S. health care costs to manage short- and long-term prematurity complications are estimated to exceed $25 billion.Clinical interventions, including case management (increased patient outreach, education and specialist care), pharmacological treatment and their combination can provide benefit to pregnancies at higher risk for preterm birth. Early and sensitive risk detection, however, remains a challenge.We have developed and validated a proteomic biomarker risk predictor for early identification of pregnancies at increased risk of preterm birth. The ACCORDANT study modeled treatments with real-world patient data from a racially and ethnically diverse U.S. population to compare the benefits of risk predictor testing plus clinical intervention for higher-risk pregnancies versus no testing and standard care. Measured outcomes included neonatal and maternal length of hospital stay, associated costs and neonatal morbidity and mortality. The model projected improved outcomes and reduced costs across all subjects, including ethnic and racial minority populations, when predicted higher-risk pregnancies were treated using case management with or without pharmacological treatment. The biomarker risk predictor shows high potential to be a clinically important component of risk stratification for pregnant women, leading to tangible gains in reducing the impact of preterm birth.

Better Estimation of Spontaneous Preterm Birth Prediction Performance through Improved Gestational Age Dating.

The clinical management of pregnancy and spontaneous preterm birth (sPTB) relies on estimates of gestational age (GA). Our objective was to evaluate the effect of GA dating uncertainty on the observed performance of a validated proteomic biomarker risk predictor, and then to test the generalizability of that effect in a broader range of GA at blood draw. In a secondary analysis of a prospective clinical trial (PAPR; NCT01371019), we compared two GA dating categories: both ultrasound and dating by last menstrual period (LMP) (all subjects) and excluding dating by LMP (excluding LMP). The risk predictor's performance was observed at the validated risk predictor threshold both in weeks 191/7-206/7 and extended to weeks 180/7-206/7. Strict blinding and independent statistical analyses were employed. The validated biomarker risk predictor showed greater observed sensitivity of 88% at 75% specificity (increases of 17% and 1%) in more reliably dated (excluding-LMP) subjects, relative to all subjects. Excluding dating by LMP significantly improved the sensitivity in weeks 191/7-206/7. In the broader blood draw window, the previously validated risk predictor threshold significantly stratified higher and lower risk of sPTB, and the risk predictor again showed significantly greater observed sensitivity in excluding-LMP subjects. These findings have implications for testing the performance of models aimed at predicting PTB.

A double-blinded randomized controlled trial on the effects of increased intravenous hydration in nulliparas undergoing induction of labor.

BACKGROUND: Rates of labor induction are increasing, raising concerns related to increased healthcare utilization costs. High-dose intravenous fluid (250 cc/h) has been previously demonstrated to shorten the time to delivery in nulliparous individuals in spontaneous labor. Whether or not this relationship exists among individuals undergoing induction of labor is unknown. OBJECTIVE: Our study aimed to evaluate the effect of high-dose intravenous hydration on time to delivery among nulliparous individuals undergoing induction of labor. STUDY DESIGN: Nulliparous individuals presenting for induction of labor with a Bishop score of ≤6 (with and without rupture of membranes) were randomized to receive either 125 cc/h or 250 cc/h of normal saline. The primary outcome was length of labor (defined as time from initiation of study fluids to delivery). Both time to overall delivery and vaginal delivery were evaluated. Secondary outcomes included the lengths of each stage of labor, the percentage of individuals delivering within 24 hours, and maternal and neonatal outcomes, including cesarean delivery rate. RESULTS: A total of 180 individuals meeting inclusion criteria were enrolled and randomized. Baseline demographic characteristics were similar between groups; however, there was a higher incidence of diabetes mellitus in the group receiving 125 cc/h. Average length of labor was similar between groups (27.6 hours in 250 cc/h and 27.8 hours in 125 cc/h), as was the length of each stage of labor. Cox regression analysis did not demonstrate an effect of fluid rate on time to delivery. Neither the admission Bishop score, body mass index, nor other demographic characteristics affected time to delivery or vaginal delivery. There were no differences in maternal or neonatal outcomes, including overall cesarean delivery rate, clinically apparent iatrogenic intraamniotic infection, Apgar scores, need for neonatal phototherapy, or neonatal intensive care unit stay. CONCLUSION: There were no observed differences in the length of labor or maternal or neonatal outcomes with the administration of an increased rate of intravenous fluids among nulliparous individuals undergoing induction of labor.

Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study.

Preterm births are the leading cause of neonatal death in the United States. Previously, a spontaneous preterm birth (sPTB) predictor based on the ratio of two proteins, IBP4/SHBG, was validated as a predictor of sPTB in the Proteomic Assessment of Preterm Risk (PAPR) study. In particular, a proteomic biomarker threshold of -1.37, corresponding to a ~two-fold increase or ~15% risk of sPTB, significantly stratified earlier deliveries. Guidelines for molecular tests advise replication in a second independent study. Here we tested whether the significant association between proteomic biomarker scores above the threshold and sPTB, and associated adverse outcomes, was replicated in a second independent study, the Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor (TREETOP). The threshold significantly stratified subjects in PAPR and TREETOP for sPTB (p = 0.041, p = 0.041, respectively). Application of the threshold in a Kaplan-Meier analysis demonstrated significant stratification in each study, respectively, for gestational age at birth (p < 001, p = 0.0016) and rate of hospital discharge for both neonate (p < 0.001, p = 0.005) and mother (p < 0.001, p < 0.001). Above the threshold, severe neonatal morbidity/mortality and mortality alone were 2.2 (p = 0.0083,) and 7.4-fold higher (p = 0.018), respectively, in both studies combined. Thus, higher predictor scores were associated with multiple adverse pregnancy outcomes.

Is Exposure to Intrapartum Prostaglandins for Labor Induction Associated with a Lower Incidence of Neonatal Respiratory Distress Syndrome?

OBJECTIVE: Respiratory distress syndrome (RDS) is implicated in 30% of neonatal deaths. Since prostaglandins promote surfactant secretion and labor is associated with a lower risk of RDS in term neonates, it is plausible that synthetic prostaglandin (sPG) exposure is associated with a lower risk of RDS. Thus, we evaluated the association between sPG exposure and RDS in neonates born after the induction of labor (IOL). STUDY DESIGN: Secondary analysis of women with singleton pregnancies undergoing IOL at 340/7 to 420/7 weeks in the nuMoM2b study, a multicenter prospective cohort of nulliparous women. RDS rates and secondary neonatal outcomes in neonates with intrapartum sPG exposure were compared with those who had IOL with non-sPG methods (e.g., balloon catheter, amniotomy, oxytocin, and laminaria). Logistic regression models estimated the association of sPG with RDS and with secondary outcomes after adjustment for clinical and demographic factors (including gestational age). A sensitivity analysis was performed in which analysis was restricted to those with an admission cervical dilation ≤2 cm. RESULTS: Of 10,038 women in the total cohort, 3,071 met inclusion criteria; 1,444 were exposed and 1,627 were unexposed to sPGs. Antenatal corticosteroid exposure rates were low (3.0%) and similar between groups. In univariable analysis, neonates with sPG exposure had higher rates of RDS (3.2 vs. 2.0%, odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.01-2.50). This relationship was similar by gestational age at delivery (term vs. preterm, interaction p = 0.14). After adjustment, the association between sPG and RDS was no longer significant (adjusted odds ratio: 1.4, 95% CI: 0.9-2.3). When analysis was restricted to subjects with admission cervical dilation of ≤2 cm, there was also no association between sPG exposure and RDS. CONCLUSION: In pregnancies between 34 and 42 weeks of gestation, exposure to sPG for cervical ripening or labor induction was not associated with newborn RDS. KEY POINTS: · RDS is implicated in 30% of neonatal deaths.. · sPG exposure was not associated with RDS.. · Avoiding preterm birth remains crucial in RDS prevention..

Evaluation of a novel screening method for fetal aneuploidy using cell-free DNA in maternal plasma.

Objective: To evaluate the test performance of a novel sequencing technology using molecular inversion probes applied to cell-free DNA screening for fetal aneuploidy. Methods: Two cohorts were included in the evaluation; a risk-based cohort of women receiving diagnostic testing in the first and second trimesters was combined with stored samples from pregnancies with fetuses known to be aneuploid or euploid. All samples were blinded to testing personnel before being analyzed, and validation occurred after the study closed and results were merged. Results: Using the new sequencing technology, 1414 samples were analyzed. The findings showed sensitivities and specificities for the common trisomies and the sex chromosome aneuploidies at >99% (Trisomy 21 sensitivity 99.2 CI 95.6­99.2; specificity 99.9 CI 99.6­99.9). Positive predictive values among the trisomies varied from 85.2% (Trisomy 18) to 99.0% (Trisomy 21), reflecting their prevalence rates in the study. Comparisons with a meta-analysis of recent cell-free DNA screening publications demonstrated equivalent test performance. Conclusion: This new technology demonstrates equivalent test performance compared with alternative sequencing approaches, and demonstrates that each chromosome can be successfully interrogated using a single probe.

Estimating risk of severe neonatal morbidity in preterm births under 32 weeks of gestation.

Background: A large recent study analyzed the relationship between multiple factors and neonatal outcome and in preterm births. Study variables included the reason for admission, indication for delivery, optimal steroid use, gestational age, and other potential prognostic factors. Using stepwise multivariable analysis, the only two variables independently associated with serious neonatal morbidity were gestational age and the presence of suspected intrauterine growth restriction as a reason for admission. This finding was surprising given the beneficial effects of antenatal steroids and hazards associated with some causes of preterm birth. Multivariable logistic regression techniques have limitations. Without testing for multiple interactions, linear regression will identify only individual factors with the strongest independent relationship to the outcome for the entire study group. There may not be a single "best set" of risk factors or one set that applies equally well to all subgroups. In contrast, machine learning techniques find the most predictive groupings of factors based on their frequency and strength of association, with no attempt to identify independence and no assumptions about linear relationships.Objective: To determine if machine learning techniques would identify specific clusters of conditions with different probability estimates for severe neonatal morbidity and to compare these findings to those based on the original multivariable analysis.Materials and methods: This was a secondary analysis of data collected in a multicenter, prospective study on all admissions to the neonatal intensive care unit between 2013 and 2015 in 10 hospitals. We included all patients with a singleton, stillborn, or live newborns, with a gestational age between 23 0/7 and 31 6/7 week. The composite endpoint, severe neonatal morbidity, defined by the presence of any of five outcomes: death, grade 3 or 4 intraventricular hemorrhage (IVH), and ≥28 days on ventilator, periventricular leukomalacia (PVL), or stage III necrotizing enterocolitis (NEC), was present in 238 of the 1039 study patients. We studied five explanatory variables: maternal age, parity, gestational age, admission reason, and status with respect to antenatal steroid administration. We concentrated on Classification and Regression Trees because the resulting structure defines clusters of risk factors that often bear resemblance to clinical reasoning. Model performance was measured using area under the receiver-operator characteristic curves (AUC) based on 10 repetitions of 10-fold cross-validation.Results: A hybrid technique using a combination of logistic regression and Classification and Regression Trees had a mean cross-validated AUC of 0.853. A selected point on its receiver-operator characteristic (ROC) curve corresponding to a sensitivity of 81% was associated with a specificity of 76%. Rather than a single curve representing the general relationship between gestational age and severe morbidity, this technique found seven clusters with distinct curves. Abnormal fetal testing as a reason for admission with or without growth restriction and incomplete steroid administration would place a 20-year-old patient on the highest risk curve.Conclusions: Using a relatively small database and a few simple factors known before birth it is possible to produce a more tailored estimate of the risk for severe neonatal morbidity on which clinicians can superimpose their medical judgment, experience, and intuition.

Cervical Pessary versus Expectant Management for the Prevention of Delivery Prior to 36 Weeks in Women with Placenta Previa: A Randomized Controlled Trial.

Objective This multicenter randomized controlled trial compared cervical pessary (CP) versus expectant management (EM) in women with placenta previa between 22.0 and 32.0 in prolonging gestation until ≥ 36.0 weeks' gestation. Study Design This study took place from November 2016 to June 2018. Women were randomized to receive either the Bioteque CP or EM. The pessary was removed at ≥ 36.0 weeks unless indicated. The primary outcome was gestational age (GA) at delivery, with secondary outcomes including need for transfusion, number and duration of antepartum admissions, type of delivery, and neonatal outcomes. A total of 140 patients were needed to show a 3-week prolongation of pregnancy in the pessary group; however, the trial was stopped early due to budgetary issues. Results Of the 33 eligible women, 17 were enrolled. Although not statistically significant, the mean GA at delivery in the CP group was greater than women in the EM group (36.5 ± 1.23 vs. 36.0 ± 2.0; p = 0.1673). The number and duration of antepartum admissions was greater in the EM group (2.7 ± 0.58 vs. 16.0 ± 22.76 days; p = 0.1264) as well. Conclusion Although the study was underpowered to determine the primary outcome, safety and feasibility of CP in pregnancies complicated with previa were demonstrated.

Effects of repeat prenatal corticosteroids given to women at risk of preterm birth: An individual participant data meta-analysis.

BACKGROUND: Infants born preterm compared with infants born at term are at an increased risk of dying and of serious morbidities in early life, and those who survive have higher rates of neurological impairments. It remains unclear whether exposure to repeat courses of prenatal corticosteroids can reduce these risks. This individual participant data (IPD) meta-analysis (MA) assessed whether repeat prenatal corticosteroid treatment given to women at ongoing risk of preterm birth in order to benefit their infants is modified by participant or treatment factors. METHODS AND FINDINGS: Trials were eligible for inclusion if they randomised women considered at risk of preterm birth who had already received an initial, single course of prenatal corticosteroid seven or more days previously and in which corticosteroids were compared with either placebo or no placebo. The primary outcomes for the infants were serious outcome, use of respiratory support, and birth weight z-scores; for the children, they were death or any neurosensory disability; and for the women, maternal sepsis. Studies were identified using the Cochrane Pregnancy and Childbirth search strategy. Date of last search was 20 January 2015. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. IPD were analysed using a one-stage approach. Eleven trials, conducted between 2002 and 2010, were identified as eligible, with five trials being from the United States, two from Canada, and one each from Australia and New Zealand, Finland, India, and the United Kingdom. All 11 trials were included, with 4,857 women and 5,915 infants contributing data. The mean gestational age at trial entry for the trials was between 27.4 weeks and 30.2 weeks. There was no significant difference in the proportion of infants with a serious outcome (relative risk [RR] 0.92, 95% confidence interval [CI] 0.82 to 1.04, 5,893 infants, 11 trials, p = 0.33 for heterogeneity). There was a reduction in the use of respiratory support in infants exposed to repeat prenatal corticosteroids compared with infants not exposed (RR 0.91, 95% CI 0.85 to 0.97, 5,791 infants, 10 trials, p = 0.64 for heterogeneity). The number needed to treat (NNT) to benefit was 21 (95% CI 14 to 41) women/fetus to prevent one infant from needing respiratory support. Birth weight z-scores were lower in the repeat corticosteroid group (mean difference -0.12, 95%CI -0.18 to -0.06, 5,902 infants, 11 trials, p = 0.80 for heterogeneity). No statistically significant differences were seen for any of the primary outcomes for the child (death or any neurosensory disability) or for the woman (maternal sepsis). The treatment effect varied little by reason the woman was considered to be at risk of preterm birth, the number of fetuses in utero, the gestational age when first trial treatment course was given, or the time prior to birth that the last dose was given. Infants exposed to between 2-5 courses of repeat corticosteroids showed a reduction in both serious outcome and the use of respiratory support compared with infants exposed to only a single repeat course. However, increasing numbers of repeat courses of corticosteroids were associated with larger reductions in birth z-scores for weight, length, and head circumference. Not all trials could provide data for all of the prespecified subgroups, so this limited the power to detect differences because event rates are low for some important maternal, infant, and childhood outcomes. CONCLUSIONS: In this study, we found that repeat prenatal corticosteroids given to women at ongoing risk of preterm birth after an initial course reduced the likelihood of their infant needing respiratory support after birth and led to neonatal benefits. Body size measures at birth were lower in infants exposed to repeat prenatal corticosteroids. Our findings suggest that to provide clinical benefit with the least effect on growth, the number of repeat treatment courses should be limited to a maximum of three and the total dose to between 24 mg and 48 mg.

"Doing something" about the cesarean delivery rate.

There is a general consensus that the cesarean delivery rate in the United States is too high, and that practice patterns of obstetricians are largely to blame for this situation. In reality, the US cesarean delivery rate is the result of 3 forces largely beyond the control of the practicing clinician: patient expectations and misconceptions regarding the safety of labor, the medical-legal system, and limitations in technology. Efforts to "do something" about the cesarean delivery rate by promulgating practice directives that are marginally evidence-based or influenced by social pressures are both ineffective and potentially harmful. We examine both the recent American Congress of Obstetricians and Gynecologists (ACOG)/Society for Maternal-Fetal Medicine Care Consensus Statement "Safe Prevention of Primary Cesarean Delivery" document and the various iterations of the ACOG guidelines for vaginal birth after cesarean delivery in this context. Adherence to arbitrary time limits for active phase or second-stage arrest without incorporating other clinical factors into the decision-making process is unwise. In a similar manner, ever-changing practice standards for vaginal birth after cesarean driven by factors other than changing data are unlikely to be effective in lowering the cesarean delivery rate. Whether too high or too low, the current US cesarean delivery rate is the expected result of the unique demographic, geographic, and social forces driving it and is unlikely to change significantly given the limitations of current technology to otherwise satisfy the demands of these forces.

A multicenter prospective study of neonatal outcomes at less than 32 weeks associated with indications for maternal admission and delivery.

BACKGROUND: Counseling for patients with impending premature delivery traditionally has been based primarily on the projected gestational age at delivery. There are limited data regarding how the indications for the preterm birth affect the neonatal outcome and whether this issue should be taken into account in decisions regarding management and patient counseling. OBJECTIVE: We performed a prospective study of pregnancies resulting in premature delivery at less than 32 weeks to determine the influence of both the indications for admission and their associated indications for delivery on neonatal mortality and complications of prematurity. STUDY DESIGN: This is a multicenter, prospective study in 10 hospitals where all data from the neonatal intensive care unit routinely was imported to a deidentified data warehouse. Maternal data were collected prospectively at or near the time of delivery. Eligible subjects included singleton deliveries in these hospitals between 23 0/7 and 31 6/7 weeks. The primary hypothesis of the study was to determine whether there was a difference in the primary outcome, which was defined as neonatal composite morbidity, between those neonates delivered after admission for premature labor vs premature rupture of membranes, because these were expected to be the 2 most frequent diagnoses leading to premature birth. The sample size was calculated based on a 10% difference in outcomes for these 2 entities. We based this hypothesis on the knowledge that premature rupture of membranes has a greater incidence of intra-amniotic infection and inflammation than premature labor and that outcomes for premature neonates are worse when delivery is associated with intra-amniotic infection. Additional outcomes were analyzed for all other indications for admission and delivery. Composite morbidity was defined as ≥1 of the following: respiratory distress syndrome (oxygen requirement, clinical diagnosis, and consistent chest radiograph), bronchopulmonary dysplasia (requirement for oxygen support at 28 days of life), severe intraventricular hemorrhage (grades 3 or 4), periventricular leukomalacia, blood culture-proven sepsis present within 72 hours of birth, necrotizing enterocolitis, or neonatal death before discharge from the hospital. A secondary composite of serious neonatal morbidity also was defined prospectively. RESULTS: The study included 1089 mother/baby pairs. Composite morbidity between those with premature labor (77.2%) and premature rupture of membranes (73.2%) was not significantly different (P = .29). A few neonatal complications were associated with indications for admission and delivery, but on logistic regression adjusting for gestational age and other confounders, suspected intrauterine growth restriction was the only indication for admission or delivery associated with an increase in serious morbidity (odds ratio 4.5, [2.1 to 9.8], P < .003). Other factors not related to the indications for admission including cesarean delivery, and low 5-minute Apgar were associated with an increase in morbidity. CONCLUSION: Studies of many single factors related to the indications for preterm delivery have been shown to be associated with adverse neonatal outcome. In this study evaluating all of the most frequent indications, however, we found only suspected intrauterine growth restriction as an indication for admission and delivery was found to be so. Thus, it seems that in almost all situations counseling patients can be based primarily on gestational age along with other factors including estimated fetal weight, sex, race, plurality, and completion of a course of antenatal corticosteroids.

A randomized, double-blinded, controlled trial of the effects of fluid rate and/or presence of dextrose in intravenous fluids on the labor course of nulliparas.

BACKGROUND: Prolonged labor has been demonstrated to increase adverse maternal and neonatal outcome. A practice that may decrease the risk of prolonged labor is the modification of fluid intake during labor. OBJECTIVE: Several studies demonstrated that increased hydration in labor as well as addition of dextrose-containing fluids may be associated with a decrease in length of labor. The purpose of our study was to characterize whether high-dose intravenous fluids, standard-dose fluids with dextrose, or high-dose fluids with dextrose show a difference in the duration of labor in nulliparas. STUDY DESIGN: Nulliparous subjects with singletons who presented in active labor were randomized to 1 of 3 groups of intravenous fluids: 250 mL/h of normal saline, 125 mL/h of 5% dextrose in normal saline, or 250 mL/h of 2.5% dextrose in normal saline. The primary outcome was total length of labor from initiation of intravenous fluid in vaginally delivered subjects. Secondary outcomes included cesarean delivery rate and length of second stage of labor, among other maternal and neonatal outcomes. RESULTS: In all, 274 subjects who met inclusion criteria were enrolled. There were no differences in baseline characteristics among the 3 groups. There was no difference in the primary outcome of total length of labor in vaginally delivered subjects among the 3 groups. First stage of labor duration, second stage of labor duration, and cesarean delivery rates were also equivalent. There were no differences identified in other secondary outcomes including clinical chorioamnionitis, postpartum hemorrhage, blood loss, Apgar scores, or neonatal intensive care admission. CONCLUSION: There is no difference in length of labor or delivery outcomes when comparing high-dose intravenous fluids, addition of dextrose, or use of high-dose intravenous fluids with dextrose in nulliparous women who present in active labor.

Exposure to any antenatal corticosteroids and outcomes in preterm infants by gestational age: prospective cohort study.

Objective To determine whether exposure to any antenatal corticosteroids is associated with a lower rate of death at each gestational age at which administration is currently recommended.Design Prospective cohort study.Settings 300 participating neonatal intensive care units of the Pediatrix Medical Group in the United States.Participants 117 941 infants 23 0/7 to 34 6/7 weeks' gestational age born between 1 January 2009 and 31 December 2013.Exposure Any antenatal corticosteroids.Main outcomes measures Death or major hospital morbidities analyzed by gestational age and exposure to antenatal corticosteroids with models adjusted for birth weight, sex, mode of delivery, and multiple births.Results Infants exposed to antenatal corticosteroids (n=81 832) had a significantly lower rate of death before discharge at each gestation 29 weeks or less, 31 weeks, and 33-34 weeks compared with infants without exposure (range of adjusted odds ratios 0.32 to 0.55). The number needed to treat with antenatal corticosteroids to prevent one death before discharge increased from six at 23 and 24 weeks' gestation to 798 at 34 weeks' gestation. The rate of survival without major hospital morbidity was higher among infants exposed to antenatal corticosteroids at the lowest gestations. Infants exposed to antenatal corticosteroids had lower rates of severe intracranial hemorrhage or death, necrotizing enterocolitis stage 2 or above or death, and severe retinopathy of prematurity or death compared with infants without exposure at all gestations less than 30 weeks and most gestations for infants born at 30 weeks' gestation or later.Conclusion Among infants born from 23 to 34 weeks' gestation, antenatal exposure to corticosteroids compared with no exposure was associated with lower mortality and morbidity at most gestations. The effect size of exposure to antenatal corticosteroids on mortality seems to be larger in infants born at the lowest gestations.

The limits of electronic fetal heart rate monitoring in the prevention of neonatal metabolic acidemia.

BACKGROUND: Despite intensive efforts directed at initial training in fetal heart rate interpretation, continuing medical education, board certification/recertification, team training, and the development of specific protocols for the management of abnormal fetal heart rate patterns, the goals of consistently preventing hypoxia-induced fetal metabolic acidemia and neurologic injury remain elusive. OBJECTIVE: The purpose of this study was to validate a recently published algorithm for the management of category II fetal heart rate tracings, to examine reasons for the birth of infants with significant metabolic acidemia despite the use of electronic fetal heart rate monitoring, and to examine critically the limits of electronic fetal heart rate monitoring in the prevention of neonatal metabolic acidemia. STUDY DESIGN: The potential performance of electronic fetal heart rate monitoring under ideal circumstances was evaluated in an outcomes-blinded examination fetal heart rate tracing of infants with metabolic acidemia at birth (base deficit, >12) and matched control infants (base deficit, <8) under the following conditions: (1) expert primary interpretation, (2) use of a published algorithm that was developed and endorsed by a large group of national experts, (3) assumption of a 30-minute period of evaluation for noncritical category II fetal heart rate tracings, followed by delivery within 30 minutes, (4) evaluation without the need to provide patient care simultaneously, and (5) comparison of results under these circumstances with those achieved in actual clinical practice. RESULTS: During the study period, 120 infants were identified with an arterial cord blood base deficit of >12 mM/L. Matched control infants were not demographically different from subjects. In actual practice, operative intervention on the basis of an abnormal fetal heart rate tracings occurred in 36 of 120 fetuses (30.0%) with metabolic acidemia. Based on expert, algorithm-assisted reviews, 55 of 120 patients with acidemia (45.8%) were judged to need operative intervention for abnormal fetal heart rate tracings. This difference was significant (P=.016). In infants who were born with a base deficit of >12 mM/L in which blinded, algorithm-assisted expert review indicated the need for operative delivery, the decision for delivery would have been made an average of 131 minutes before the actual delivery. The rate of expert intervention for fetal heart rate concerns in the nonacidemic control group (22/120; 18.3%) was similar to the actual intervention rate (23/120; 19.2%; P=1.0) Expert review did not mandate earlier delivery in 65 of 120 patients with metabolic acidemia. The primary features of these 65 cases included the occurrence of sentinel events with prolonged deceleration just before delivery, the rapid deterioration of nonemergent category II fetal heart rate tracings before realistic time frames for recognition and intervention, and the failure of recognized fetal heart rate patterns such as variability to identify metabolic acidemia. CONCLUSIONS: Expert, algorithm-assisted fetal heart rate interpretation has the potential to improve standard clinical performance by facilitating significantly earlier recognition of some tracings that are associated with metabolic acidemia without increasing the rate of operative intervention. However, this improvement is modest. Of infants who are born with metabolic acidemia, only approximately one-half potentially could be identified and have delivery expedited even under ideal circumstances, which are probably not realistic in current US practice. This represents the limits of electronic fetal heart rate monitoring performance. Additional technologies will be necessary if the goal of the prevention of neonatal metabolic acidemia is to be realized.