Childhood neurodevelopment after spontaneous versus indicated preterm birth.

BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality. Individuals who survive preterm birth are at a higher risk for many long-term adverse effects, including neurodevelopmental deficits. There are many well-established risk factors for worse neurologic outcomes spanning the prenatal and postnatal periods; however, investigators have yet to assess whether the cause of preterm birth has an impact on neurodevelopment. OBJECTIVE: Our objective was to assess whether neurologic outcomes differ by children born via indicated versus spontaneous preterm birth. STUDY DESIGN: We performed secondary analysis of a multicenter trial assessing magnesium for neuroprotection in women at risk for preterm delivery from 24 to 31 weeks. We included women with live, nonanomalous, singleton gestations who delivered preterm; we excluded women whose children were missing 2-year follow-up information for reasons other than perinatal demise. The primary exposure was type of preterm birth: (1) spontaneous if the child's mother presented with preterm labor or ruptured membranes, or (2) indicated if the child was delivered preterm iatrogenically. The primary outcome was death (including stillbirths, neonatal intensive care unit deaths, and deaths after discharge) or an abnormal Bayley II score by 2 years of age, defined as a Mental Developmental Index score or Psychomotor Developmental Index score 2 standard deviations below the mean. Secondary outcomes included death or Mental Developmental Index and Psychomotor Developmental Index scores 1 standard deviation or less, and neonatal morbidities associated with prematurity. Bivariate analyses of baseline characteristics by exposure were conducted. A logistic regression model was fitted to adjust for confounders. RESULTS: Of 1678 subjects, 1631 (97.2%) underwent spontaneous preterm birth and 47 (2.8%) underwent indicated preterm birth. Baseline maternal demographics and gestational age at delivery were similar between groups (29.6 weeks ± 7.8 versus 28.8 weeks ± 2.5, P = .07). A Psychomotor Developmental Index score 2 standard deviations or less below the mean or death occurred in 340 (20.9%) spontaneous preterm birth subjects and 17 (36.2%) indicated preterm birth subjects (P = .01). When adjusting for confounders, there remained an increased probability of a Psychomotor Developmental Index scores 2 standard deviations or less or death in indicated preterm birth subjects (P = .02). Although not statistically significant, indicated preterm birth was also associated with higher odds of Mental Developmental Index scores 2 standard deviations or less or death, Psychomotor Developmental scores 1 standard deviation or less or death, and Mental Developmental Index scores 1 standard deviation or less or death (1.76, 1.59, and 1.45, respectively). Limiting the analysis to small for gestational age infants, there was no difference in neurologic outcomes. The same was true for when we excluded small for gestational age infants from our analysis. However, after adjusting for small for gestational age, the odds of a Psychomotor Developmental Index score 2 standard deviations or less or death remained significant higher in the indicated preterm birth group (adjusted odds ratio, 1.98; 95% confidence interval, 1.01-3.88). CONCLUSION: In this cohort of pregnant women who delivered preterm, indicated deliveries were associated with worse psychomotor development than were spontaneous deliveries. Other outcomes appeared to be poor, but our numbers were limited. This finding should be confirmed in a larger cohort of women undergoing medically indicated preterm deliveries.

Optimizing Term Delivery and Mode of Delivery.

Full-term deliveries are defined as occurring between 39 weeks and 40 weeks and 6 days. Because contemporary research suggests improved outcomes with delivery in the term period compared with the early term period, nonindicated delivery should be pursued no earlier than 39 weeks. There are, however, multiple medical, obstetric, and fetal indications for delivery before 39 weeks, and the obstetric provider must weigh the risks and benefits of delivery versus expectant management on both the mother and fetus. This review serves to provide a basic framework of evidentiary support toward optimizing the term delivery.

Risk of Stillbirth after Antepartum Hospitalization for Hypertensive Diseases of Pregnancy.

OBJECTIVE: To determine if women with an antepartum admission for hypertensive diseases of pregnancy (HDP) were at increased risk for stillbirth. STUDY DESIGN: This study utilized the 2010 to 2014 Nationwide Readmissions Database. Antepartum admissions with HDP were identified and linked to subsequent delivery hospitalizations. Delivery hospitalizations with HDP without a preceding antepartum HDP admission were also identified. Risk for stillbirth, abruption, or both was compared between these two groups. RESULTS: An estimated 382,621 deliveries with an HDP diagnosis were identified of which 14,857 (3.9%) had a preceding antepartum admission for HDP. Stillbirth occurred in 7.8 per 1,000 delivery hospitalizations complicated by HDP with risk higher with a preceding HDP antepartum admission in both unadjusted (1.1 vs. 0.8%, risk ratios [RR] 1.46, 95% confidence interval [CI] 1.24-1.70) and adjusted (adjusted risk ratios [aRR] 1.24, 95% CI 1.06, 1.46) analyses. Abruption occurred in 19.6 per 1,000 delivery hospitalizations complicated by HDP with risk higher with a preceding HDP antepartum admission in both unadjusted (2.5 vs. 1.9%, RR 1.30, 95% CI 1.17-1.44) and adjusted (aRR 1.24, 95% CI 1.11, 1.37) analyses. Risk for combined abruption and stillbirth did not differ significantly. CONCLUSION: In this analysis, prior antenatal hospitalization was associated with increased risk for stillbirth among women with HDP.

The Effect of Prior Term Birth on Risk of Recurrent Spontaneous Preterm Birth.

OBJECTIVE: The objective of this study was to evaluate the effect of prior term birth on recurrent spontaneous preterm birth (sPTB) risk. STUDY DESIGN: Retrospective cohort study of 211 women with prior sPTB, comparing women with and without prior term births. The primary outcome was recurrent sPTB <37 weeks. Analyses stratified by gestational age of prior sPTB and adjusted for confounders using multivariable logistic regression. RESULTS: The overall sPTB rate was 33.7%, with no statistical difference between women with and without prior term births (28.9 vs. 37.7%, p = 0.2). Among women with prior second-trimester loss (16-236/7 weeks), those with a term birth had a decreased sPTB rate (15.4 vs. 43.2%, p = 0.02), which persisted after adjusting for age and 17-α hydroxyprogesterone caproate use. For women with prior sPTB ≥24 weeks, there was no difference in sPTB with and without prior term births (29.5 vs. 26.6%, p = 0.7). A term birth as the most recent delivery lowered, but did not eliminate, the sPTB risk (19.1 vs. 36.4%, p = 0.1). CONCLUSION: Prior term birth lowers the risk of recurrent sPTB for women with prior second-trimester loss, but not for women with prior sPTB ≥24 weeks. Women with prior preterm and term births should be counseled accordingly and all sPTB prevention strategies should be recommended.

Comparison of Respiratory Outcomes between Preterm Small-For-Gestational-Age and Appropriate-For-Gestational-Age Infants.

Objective This study aims to determine whether preterm infants who are small for gestational age (SGA) are more likely to have respiratory distress syndrome (RDS) compared with appropriate-for-gestational-age infants. Methods Secondary analysis of a multicenter trial evaluating magnesium for neuroprotection. Nonanomalous, singleton gestations delivered between 22 0/7 and 36 6/7 weeks were included. Large-for-gestational-age infants were excluded. We performed a nested case-control study. Cases were infants with RDS; controls were infants without RDS. The sample size estimates revealed 779 subjects/group were needed to achieve a 80% power to demonstrate a 1/3 difference in RDS. We fit a multivariable logistic regression model to adjust for confounders. We assessed the association of SGA with RDS and a composite adverse respiratory and neonatal outcome. Results Overall, 947 cases and 920 controls were included. The groups differed by gestational age at delivery, antibiotic exposure, mode of delivery, infant gender, and birth weight. SGA was not associated with RDS (adjusted odds ratio [aOR]: 1.07, 95% confidence interval [CI]: 0.48-2.38) or the composite respiratory (aOR: 0.87, 95% CI: 0.37-2.04) or adverse neonatal outcome (aOR: 0.65, 95% CI: 0.27-1.54). RDS and the composite respiratory outcome were most associated with earlier gestational age at delivery, cesarean delivery, and male gender. Conclusion SGA is not associated with RDS or other adverse respiratory and neonatal composites.

Proximity of magnesium exposure to delivery and neonatal outcomes.

BACKGROUND: In infants delivered preterm, magnesium sulfate reduces cerebral palsy in survivors. The benefit of magnesium given remote from delivery is unclear. OBJECTIVE: Our objective was to evaluate the association of time from last exposure to magnesium with cerebral palsy. STUDY DESIGN: This was a secondary analysis of a multicenter trial evaluating magnesium for neuroprotection. For this study, we included women with live, nonanomalous, singleton gestations who received magnesium. Pregnancies with missing information at the 2 year follow-up were excluded. Women were divided into 2 groups based on exposure timing: last infusion of magnesium <12 hours and last infusion of magnesium ≥12 hours prior to delivery. The primary outcome was cerebral palsy of any severity at 2 years of life. Secondary outcomes were moderate/severe cerebral palsy and moderate/severe cerebral palsy or death. A χ(2) test, Student t test, and Mann-Whitney U test were used for bivariate associations. We fit a multivariable logistic regression model to adjust for confounders. RESULTS: A total of 906 infants were analyzed. Five hundred sixty-eight were last exposed to magnesium <12 hours prior to delivery and 338 were last exposed ≥12 hours. Cerebral palsy occurred in 28 offspring (3%), 2.3% of those last exposed <12 hours vs 4.4% last exposed ≥12 hours prior to delivery (P = .07). On adjusted analyses, last exposure to magnesium <12 hours prior to delivery was associated with a significant reduction in cerebral palsy compared with last exposure ≥12 hours (adjusted odds ratio, 0.41, 95% confidence interval, 0.18-0.91, P = .03). There was no difference in secondary outcomes. CONCLUSION: Exposure to magnesium proximal to delivery (<12 hours) is associated with a reduced odds of cerebral palsy compared with more remote exposure. This highlights the importance of the timing of magnesium for neuroprotection for women at risk of preterm delivery.

A comparison of prevaginal and postvaginal manipulation fetal fibronectin.

BACKGROUND: Fetal fibronectin (fFN) is used as a biomarker for preterm delivery. Currently, its use is discouraged if there has been vaginal manipulation in the previous 24 hours. OBJECTIVE: Our objective is to determine if there are differences between fFN results before and after vaginal manipulation in the form of sterile vaginal exam or transvaginal ultrasound. STUDY DESIGN: This was a prospective observational cohort study at a single center of women between 22-33 6/7 weeks at risk for preterm delivery due to: (1) a history of preterm delivery, short cervix, or multifetal gestation; or (2) symptoms of preterm labor. We excluded women with vaginal bleeding or infection, placenta previa, ruptured membranes, cervical dilation >3 cm, or any form of vaginal manipulation in the previous 24 hours. Specimen A was collected prior to planned vaginal exam or transvaginal ultrasound and specimen B was collected within 4 hours. The agreement between specimens A and B was assessed using descriptive statistics. Test characteristics of specimens A and B using the outcome of preterm delivery (<37 weeks) were calculated. RESULTS: In all, 310 specimen pairs from 237 women were collected. Specimen A was positive in 37 (12%) instances and negative in 273 (88%) while specimen B was positive in 39 (13%) and negative in 271 (87%). There were discordant results in 26 specimen pairs. Of these, 14 (5%) negative specimen A results subsequently became positive for specimen B, and 12 (32%) positive specimen A results became negative for specimen B. Overall, there was a 92% agreement between specimens A and B (confidence interval, 88-94%). The specificity of specimens A and B for preterm birth was 90% vs 89%, respectively, with a negative predictive value of 87% for both. The false-negative rate was 12.8% for specimen A and 13.3% for specimen B. CONCLUSION: There is a moderately high degree of agreement between prevaginal and postvaginal manipulation fFN results. Their test characteristics for evaluating preterm birth are similar with strong specificity and negative predictive values, and their false-negative rates are not clinically different. Consideration should be made to the utilization of postvaginal manipulation fFN when a prevaginal manipulation specimen is not available.

Patient characteristics associated with 17-alpha hydroxyprogesterone caproate use among a high-risk cohort.

BACKGROUND: Preterm birth (PTB) remains a significant cause of neonatal morbidity and mortality. Women with a prior PTB are at risk for recurrent PTB. Treatment with 17-alpha hydroxyprogesterone caproate (17OHP-C) has become standard of care for women with prior PTB to help reduce this risk. Factors that affect a woman's decision to use this medication are largely unknown. OBJECTIVE: The objective of our study was to investigate patient-level barriers to 17OHP-C. We studied a cohort of women eligible for 17OHP-C with the hypothesis that 17OHP-C is underutilized and certain patient characteristics, such as obstetrical history, influence its use. STUDY DESIGN: A cross-sectional study of all women seen at a specialty prematurity clinic from 2009 through 2013 was performed. Women with a singleton pregnancy were included if they had a prior spontaneous PTB (sPTB). The χ(2) tests were performed for univariate analyses. Multivariable logistic regression was used to control for confounders. RESULTS: In all, 243 women had 17OHP-C recommended to them based on obstetrical history. There were 218 women with a pregnancy during our study period that were included in our analysis. A total of 163 (74.7%) had documented 17OHP-C use. Women were more likely to accept 17OHP-C if they had a history of a second-trimester loss only (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.17-4.58) or received recommendation for cerclage due to a short cervical length (OR, 4.12; 95% CI, 1.55-10.99). Women with a prior full-term birth were less likely to accept 17OHP-C (OR, 0.48; 95% CI, 0.26-0.89), especially when the prior full-term birth was subsequent rather than prior to the PTB (OR, 0.19; 95% CI, 0.08-0.47). Race, obesity, and insurance status did not impact 17OHP-C use. There was no difference in the rate of sPTB between those who used and did not use 17OHP-C (37.2 vs 34.0%, P = .7). CONCLUSION: Obstetric history impacted 17OHP-C use. This study identifies biases regarding 17OHP-C at the patient level and can be used to develop strategies to increase its use. However, the similarity in the sPTB rate between users and nonusers highlights the importance of identifying specific populations where 17OHP-C is and is not effective in preventing PTB.

Trial of labor after cesarean versus repeat cesarean in women with small-for-gestational age neonates: a secondary analysis.

OBJECTIVE: The objective of this study was to determine whether trial of labor after cesarean (TOLAC) is associated with increased risk of adverse outcomes for small-for-gestational-age (SGA) neonates. METHODS: This secondary analysis of a multicenter prospective observational study evaluated SGA neonates born to women with a single prior cesarean delivery. Nonanomalous, singleton pregnancies delivered at 24-41 weeks were included. The primary exposure was whether women underwent planned cesarean versus attempted TOLAC. Log-linear regression models were developed to characterize the relationship between TOLAC and neonatal outcomes. The primary outcome was a composite measure of neonatal morbidity and/or mortality, including death, respiratory complications, treated hypoglycemia, sepsis, neonatal intensive care unit (NICU) admission and hospital stay >5 days. RESULTS: Of 1009 patients identified, 258 underwent repeat cesarean; 751 attempted TOLAC. Controlling for age, race, body mass index, smoking, maternal disease, prior vaginal birth after cesarean, corticosteroids, prematurity and nonreassuring fetal status as indication for delivery, the composite adverse outcome was similarly likely in both groups (adjusted risk ratio (RR) 0.99, 95% confidence interval (95% CI) 0.88-1.12, p = 0.93). CONCLUSIONS: SGA infants born to women who TOLAC have similar neonatal outcomes to those who deliver by planned repeat cesarean. We conclude that TOLAC is an acceptable option for women with a prior cesarean and suspected SGA neonates.

A prediction score to assess the risk of delivering a large for gestational age infant among obese women.

OBJECTIVE: To create a prediction score incorporating both maternal clinical characteristics and sonographic measurements in an effort to more accurately determine the risk of a large for gestational age (LGA) infant in the obese gravida. METHODS: We performed a retrospective cohort study of obese women with singleton pregnancies who had a fetal ultrasound performed between 32 and 36 weeks from 1/2008 to 12/2011. LGA was defined as birth weight (BW) ≥ 90%. Clinical characteristics associated with fetal overgrowth were included in a multivariable logistic model and stepwise backwards regression was performed to identify which risk factors generated the most parsimonious predictive model. Adjusted odds ratios of covariates in the final model were used to estimate weights for each risk factor that were summed to generate a predictive score. RESULTS: Six-hundred and sixty-nine obese women were included. The incidence of LGA infants was 11.8%. Ultrasound estimation of fetal weight alone accurately predicted LGA in 17.7 % of cases (AUC = 0.58). The most parsimonious model to accurately predict LGA at birth included 3rd trimester ultrasound EFW >90th percentile, interval from scan to delivery, and maternal history of diabetes mellitus (DM) (AUC = 0.74). A positive prediction score test result was associated with 92% specificity and 89% negative predictive value. CONCLUSIONS: A clinical prediction rule was developed and internally validated to predict the risk of an LGA infant among obese women. The ability to calculate a prediction score at the time of delivery is appealing to the clinician in order to accurately counsel women regarding the risks surrounding the delivery.

Ischemic heart disease in pregnancy.

While ischemic heart disease in reproductive-age women is rare, cardiac disease is a leading cause of maternal mortality. In turn, coronary artery disease is one of the most common causes of maternal cardiac death. The incidence of coronary artery disease in pregnancy may be rising due to the increasing prevalence of comorbid risk factors. Diagnosis and clinical management of ischemic cardiac disease is largely similar in the pregnant and non-pregnant patient, and the majority of medications and diagnostic and interventional procedures are compatible with pregnancy with a few important exceptions. Care for ischemic cardiac disease in pregnancy may be suboptimal because: (1) diagnosis is delayed because many symptoms of ischemic cardiac disease are common in pregnancy, (2) a diagnostic workup is insufficiently thorough, and/or (3) consultants may be hesitant to perform diagnostic and interventional procedures in obstetric patients. Obstetric providers should be aware of the possibility of ischemic cardiac disease in pregnancy, particularly in patients with comorbid risk factors. If ischemic cardiac disease is suspected, a thorough workup should be performed.

Isolated abdominal circumference < 5% or estimated fetal weight 10 to 19% as predictors of small for gestational age infants.

OBJECTIVES: To determine whether (1) isolated fetal abdominal circumference < 5% (AC5) in absence of growth restriction (estimated fetal weight < 10% [EFW10]) or (2) borderline fetal growth 10 to 19% (EFW10-19) predicts subsequent fetal and/or neonatal growth restriction. STUDY DESIGN: The authors performed a retrospective cohort study (January 2008 to December 2011) of women with singleton pregnancies between 26 and 36 weeks who had ≥ 1 growth ultrasound. Univariable and multivariable analyses were performed to determine the association between isolated AC5 or EFW10-19 with both subsequent sonographic diagnosis of EFW10 and neonatal diagnosis of small for gestational age (SGA). Test characteristics were calculated. RESULTS: Out of the 10,642 pregnancies, prevalence of isolated AC5, EFW10-19, EFW10, and SGA were as follows: AC5, 5.31%; EFW10-19, 13.30%; EFW10, 7.95%; and SGA, 17.63%. While screening for SGA using EFW10 alone would miss 68.34% of SGA neonates, using isolated AC5 would identify an additional 16.15% of SGA neonates with a 3.7% false positive rate. Using EFW10-19 would identify an additional 40.20% of SGA neonates with a 9.0% false positive rate. CONCLUSION: Fetuses with isolated AC5 or EFW10-19 are at an increased risk of growth restriction. Using isolated AC5 or composite EFW10-19 would identify SGA neonates that are missed using conventional sonographic definitions of growth restriction alone.

Can vibroacoustic stimulation improve the efficiency of a tertiary care antenatal testing unit?

OBJECTIVE: Our primary objective was to determine whether vibroacoustic stimulation (VAS) decreases time to fetal reactivity in the antenatal testing unit (ATU) of a tertiary care center. METHODS: We performed a prospective, quality assurance initiative to determine whether VAS could increase the efficiency of our ATU. On pre-specified "VAS days," VAS was applied for 3 s, if the non-stress test was non-reactive in the first 10 min. Generalized estimating equations models were used to account for within subject correlation due to multiple appointments per patient. RESULTS: VAS use was associated with a 3.76-min reduction in time to reactivity (21.79 vs 25.55, p = 0.011) and a 56% reduction in the need for a biophysical profile (OR: 0.44, 95% CI: 0.21-0.90). Overall, however, we found no significant decrease in time spent on the monitor or in the ATU. CONCLUSION: Compliance with a strict VAS protocol may improve the efficiency of increasingly busy ATUs.