Predictive Performance of Newborn Small for Gestational Age by a US Intrauterine versus Birth Weight-derived Standard for Short-Term Neonatal Morbidity and Mortality

Objective: The use of birth weight standards to define small for gestational age (SGA) may fail to identify neonates affected by poor fetal growth since they include births associated with sub-optimal fetal growth. Our objective was to compare intrauterine versus birth weight-derived standards to define newborn SGA to predict neonatal morbidity and mortality. Study Design: This was a secondary analysis of a multi-center observational study of 118,422 births. Liveborn singleton, non-anomalous newborns born at 23–41 weeks were included. Those with missing gestational age estimation or without a 1st or 2nd trimester ultrasound to confirm dating, birth weight, or neonatal outcome data were excluded. Birth weight percentile was computed using an intrauterine standard (Hadlock, Radiology 1991) and a birth weight-derived standard (Olsen, Pediatrics 2010). We compared the test characteristics of SGA (birth weight \u3c10th percentile) by each standard to predict a composite neonatal morbidity and mortality outcome (death prior to discharge, NICU admission \u3e48 hours, respiratory distress syndrome, sepsis, necrotizing enterocolitis, grade III or IV intraventricular hemorrhage, or seizures). Severe composite morbidity was analyzed as a secondary outcome and was defined as death, NICU admission \u3e7 days, NEC, grade 3–4 IVH, or seizures. The areas under the curve (AUC) using receiver-operating characteristic methodology and proportions of the primary outcome by SGA status were compared by gestational age category at birth (\u3c34, 340–366, ≥37 weeks). Results: Of 115,502 mother-newborn dyads in the parent study, 78,203 (67.7%) were included, with the majority of exclusions occurring because of missing or inadequate dating information, multiple gestations, or delivery outside the gestational age range. The primary composite outcome occurred in 9.5% (95% CI 9.3–9.7) and the severe composite outcome occurred in 5.3% (5.1–5.4). SGA was diagnosed by intrauterine and birth weight-derived standards in 14.8% and 7.4%, respectively (p\u3c0.001). Neonates considered SGA only by the intrauterine standard experienced the primary outcome more than twice as often as those considered non-SGA by both standards (18.4% vs 7.9%, p\u3c0.001). For prediction of the primary outcome, SGA by the intrauterine standard had higher sensitivity (29% vs 15%, p\u3c0.001) but lower specificity (87% vs 93%, p\u3c0.001) than by the birth weight standard. Both standards had weak performance overall, though the intrauterine standard had a higher AUC (0.58 vs 0.53, p\u3c0.001). When sub-analyzed by gestational age at birth, the difference in AUCs was only present among preterm deliveries 34 to 36 competed weeks. Neither standard demonstrated any discrimination for morbidity prediction among term births (AUC = 0.50 for both). When prediction of severe morbidity was compared, the intrauterine still had better overall prediction than the birth weight standard (AUC 0.65 vs 0.57, p\u3c0.001), though this also varied by gestational age at birth. Conclusion: Among non-anomalous neonates, neither intrauterine nor birth weight-derived standards for SGA accurately predicted neonatal morbidity and mortality, with no discriminatory ability at term. SGA intrauterine standards performed better than birth weight standards

Differential Gene Expression in Cord Blood of Infants Diagnosed with Cerebral Palsy: A Pilot Analysis of the Beneficial Effects of Antenatal Magnesium Cohort

The Beneficial Effects of Antenatal Magnesium clinical trial was conducted between 1997 and 2007, and demonstrated a significant reduction in cerebral palsy (CP) in preterm infants who were exposed to peripartum magnesium sulfate (MgSO4). However, the mechanism by which MgSO4 confers neuroprotection remains incompletely understood. Cord blood samples from this study were interrogated during an era when next-generation sequencing was not widely accessible and few gene expression differences or biomarkers were identified between treatment groups. Our goal was to use bulk RNA deep sequencing to identify differentially expressed genes comparing the following four groups: newborns who ultimately developed CP treated with MgSO4 or placebo, and controls (newborns who ultimately did not develop CP) treated with MgSO4 or placebo. Those who died after birth were excluded. We found that MgSO4 upregulated expression of SCN5A only in the control group, with no change in gene expression in cord blood of newborns who ultimately developed CP. Regardless of MgSO4 exposure, expression of NPBWR1 and FTO was upregulated in cord blood of newborns who ultimately developed CP compared with controls. These data support that MgSO4 may not exert its neuroprotective effect through changes in gene expression. Moreover, NPBWR1 and FTO may be useful as biomarkers and may suggest new mechanistic pathways to pursue in understanding the pathogenesis of CP. The small number of cases ultimately available for this secondary analysis, with male predominance and mild CP phenotype, is a limitation of the study. In addition, differentially expressed genes were not validated by qRT-PCR

Family History of Venous Thromboembolism and Identifying Factor V Leiden Carriers During Pregnancy

To estimate whether there is a correlation between family history of venous thromboembolism and factor V Leiden mutation carriage in gravid women without personal history of venous thromboembolism

Maternal Diabetes and Intrapartum Fetal Electrocardiogram

Objective: Fetal electrocardiogram (ECG) ST-changes are associated with fetal cardiac hypoxia. Our objective was to evaluate ST-changes by maternal diabetic status and stage of labor. Methods: Secondary analysis of a multi-centered randomized-controlled trial in which laboring patients with singleton gestations underwent fetal ECG scalp electrode placement and were randomly assigned to masked or unmasked ST-segment readings. Our primary outcome was the frequency of fetal ECG tracings with ST-changes by stage of labor. ECG tracings were categorized into mutually exclusive groups (ST-depression, ST-elevation without ST-depression or no ST-changes). We compared participants with pre-gestational diabetes mellitus (DM), gestational DM (GDM), and no DM. Results: Of the 5,436 eligible individuals in the first stage of labor (95 with pre-gestational DM and 370 with GDM) 4,427 progressed to the second stage. ST-depression occurred more frequently in the first stage of labor in participants with pre-gestational DM (15%, aOR 2.20, 95% CI 1.14-4.24) and with GDM (9.5%, aOR 1.51, 95% CI 1.02-2.25) as compared with participants without DM (5.7%). The frequency of ST-elevation was similar in participants with pregestational DM (33%, aOR 0.79, 95% CI 0.48-1.30) and GDM (33.2%, aOR 0.91, 95% CI 0.71-1.17) as compared with those without DM (34.2%). In the second stage, ST-depression did not occur in participants with pre-gestational DM (0%) and occurred more frequently in participants with GDM (3.5%, aOR 2.01, 95% CI 1.02-3.98) as compared with those without DM (2.0%). ST-elevation occurred more frequently in participants with pregestational DM (30%, aOR 1.81, 95% CI 1.02-3.22) but not with GDM (19.0%, aOR 1.06, 95% CI 0.77-1.47) as compared with those without DM (17.8%). Conclusion: ST-changes in fetal ECG occur more frequently in fetuses of diabetic mothers during labor

Short-Term Neonatal Outcomes of Pregnancies Complicated by Maternal Obesity

BACKGROUND: Maternal obesity complicates a high number of pregnancies. The degree to which neonatal outcomes are adversely affected is unclear. OBJECTIVE: This study aimed to evaluate neonatal outcomes of pregnancies complicated by maternal obesity. STUDY DESIGN: This study was a secondary analysis of a cohort of deliveries occurring on randomly selected days at 25 hospitals from 2008 to 2011. Data were collected by certified abstractors. This analysis included singleton deliveries between 24 and 42 weeks of gestation. Body mass index was calculated on the basis of maternal height and most recent weight before delivery. Normal and overweight (reference group; body mass index, 18.5-29.9 kg/m RESULTS: Overall, 52,162 patients and their neonates were included after propensity score matching. Of these, 21,704 (41.6%) were obese, 3787 (7.3%) were morbidly obese, and 590 (1.1%) were super morbidly obese. A total of 2103 neonates (4.0%) had the composite outcome. Neonates born to pregnant people with morbid obesity had a 33% increased risk of composite neonatal morbidity compared with those in the reference group (adjusted odds ratio, 1.33; 95% confidence interval, 1.17-1.52), but no significant association was observed for persons with obesity (adjusted odds ratio, 1.05; 95% confidence interval, 0.97-1.14) or with super morbid obesity (adjusted odds ratio, 1.18; 95% confidence interval, 0.86-1.64). CONCLUSION: Compared with the reference group, gravidas with morbid obesity were at higher risk of composite neonatal morbidity

Risk-adjusted models for adverse obstetric outcomes and variation in risk-adjusted outcomes across hospitals

Regulatory bodies and insurers evaluate hospital quality using obstetrical outcomes, however meaningful comparisons should take pre-existing patient characteristics into account. Furthermore, if risk-adjusted outcomes are consistent within a hospital, fewer measures and resources would be needed to assess obstetrical quality. Our objective was to establish risk-adjusted models for five obstetric outcomes and assess hospital performance across these outcomes

Breastfeeding Initiation, Duration, and Associated Factors Among People With Hepatitis C Virus Infection

OBJECTIVE: To characterize breastfeeding behaviors and identify factors associated with breastfeeding initiation among people with hepatitis C virus (HCV) infection. METHODS: We conducted a secondary analysis of a multicenter observational cohort of pregnant people with singleton gestations and HCV seropositivity. This analysis includes individuals with data on breastfeeding initiation and excludes those with human immunodeficiency virus (HIV) co-infection. The primary outcome was self-reported initiation of breastfeeding or provision of expressed breast milk. Secondary outcomes included duration of breastfeeding. Demographic and obstetric characteristics were compared between those who initiated breastfeeding and those who did not to identify associated factors. Univariable and multivariable analyses were performed. RESULTS: Overall, 579 individuals (75.0% of participants in the parent study) were included. Of those, 362 (62.5%) initiated breastfeeding or provided breast milk to their infants, with a median duration of breastfeeding of 1.4 months (interquartile range 0.5-6.0). People with HCV viremia , defined as a detectable viral load at any point during pregnancy, were less likely to initiate breastfeeding than those who had an undetectable viral load (59.4 vs 71.9%, adjusted odds ratio [aOR] 0.61, 95% CI, 0.41-0.92). People with private insurance were more likely to initiate breastfeeding compared with those with public insurance or no insurance (80.0 vs 60.1%; aOR 2.43, 95% CI, 1.31-4.50). CONCLUSION: Although HCV seropositivity is not a contraindication to breastfeeding regardless of viral load, rates of breastfeeding initiation were lower among people with HCV viremia than among those with an undetectable viral load

The association among cytochrome P450 3A, progesterone receptor polymorphisms, plasma 17-alpha hydroxyprogesterone caproate concentrations, and spontaneous preterm birth

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

An evaluation of seasonal maternal-neonatal morbidity related to trainee cycles

BACKGROUND: The existence of the July phenomenon (worse outcomes related to the presence of new physician trainees in teaching hospitals) has been debated in the literature and media. Previous studies of the phenomenon in obstetrics are limited by the quality and detail of data. OBJECTIVE: To evaluate whether the months of June to August, when transitions in trainees occur, are associated with increased maternal and neonatal morbidity. STUDY DESIGN: Secondary analysis of an observational cohort of 115,502 mother-infant pairs that delivered at 25 hospitals from March 2008 to February 2011. Inclusion criteria were an individual who had a singleton, nonanomalous live fetus at the onset of labor, and delivered at a hospital with trainees. The primary outcomes were composites of maternal and neonatal morbidity. We evaluated the outcomes by academic quarter during which the delivery occurred, beginning July 1, and by duration of the academic year as a continuous variable. To account for clustering in outcomes at a given delivery location, we applied hierarchical logistic regression with adjustment for hospital as a random effect. RESULTS: Of 115,502 deliveries, 99,929 met the inclusion criteria. Race and ethnicity, insurance, body mass index, drug use, and the availability of 24/7 maternal-fetal medicine, anesthesia, and neonatology varied by quarter. In adjusted analysis, the frequency of the composite maternal and neonatal morbidity did not differ by quarter. No differences in composite morbidity were observed when using day of the year as a continuous variable (maternal morbidity adjusted odds ratio, 1.00; 95% confidence interval, 0.99-1.00 and neonatal morbidity adjusted odds ratio, 1.00; 95% confidence interval, 1.00-1.01) and after adjustment for hospital as a random effect. Odds of major surgical complications in quarter 2 were twice those in quarter 1. Neonatal injury and intensive care unit were less frequent in later quarters. CONCLUSION: Maternal and neonatal morbidity in teaching hospitals was not associated with the academic quarter during which delivery occurred, and there was no evidence of a July phenomenon