We sought to determine if there is an association between neighborhood socioeconomic disadvantage and group B streptococcus (GBS) colonization in pregnancy. This was a secondary analysis from the prospective cohort Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be study. Recruitment to this study occurred between 2010 and 2013. Home addresses during pregnancy were geocoded at the census tract level and linked to the 2015 Area Deprivation Index (ADI), which incorporates income, education, employment, and housing quality into a composite ranking of neighborhood socioeconomic disadvantage. ADI was categorized in quartiles from least (Q1) to most disadvantaged (Q4). The outcome was maternal GBS colonization. Poisson regression with robust error variance was used to estimate an adjusted relative risk (aRR), incorporating individual-level covariates such as age, Medicaid status, self-reported race and ethnicity, pre-pregnancy body mass index, and pregestational diabetes. Of 8,120 enrolled individuals with available GBS status and ADI data, 22.7% (n=1,846) were colonized with GBS. Maternal GBS colonization increased with neighborhood deprivation, from 20.1% in Q1 (least disadvantaged) to 29.4% in Q4 (most disadvantaged) (p< 0.001), with individuals living in Q4 having a 25% increased risk of GBS compared to those in Q1 after adjustment for confounding [adjusted risk ratio, aRR: 1.25; 95% CI: (1.10 to 1.42)]. Those in intermediate quartiles of neighborhood disadvantage (Q2 and Q3) were not more likely than those in Q1 to be colonized with GBS; 19.5% and 22.3%. Nulliparous gravidas living in the most disadvantaged neighborhoods were at increased risk of maternal GBS colonization.

Introduction: In explant cultures of human fetal membranes (FM) granulocyte-macrophage-colony-stimulating-factor (GM-CSF) mediates the inflammation-induced FM weakening seen in preterm premature rupture of the membranes (pPROM) and exogenous progesterone (P4) inhibits GM-CSF and inflammation-induced FM weakening. Here we report that GM-CSF induces P4 production within the FM which then acts in a paracrine manner to counteract GM-CSF-induced weakening. Methods: FM explants mounted in Transwell inserts were cultured with control media and increasing GM-CSF, RU486 (blocks P4 action), or trilostane (blocks P4 production). P4 production, matrix metalloproteinase-2 (MMP-2) and FM rupture strength were determined. Effects of GM-CSF on P4 production and abundance of the 3ß-hydroxysteroid dehydrogenase (3ßHSD) enzyme in the BeWo human trophoblast cell line were also determined. Results: GM-CSF induced P4 production in both FM explants and BeWo cells in a concentration-dependent manner. GM-CSF also increased 3βHSD protein in BeWo cells. Incubation of FMs with RU486, or trilostane, each caused increased FM weakening. Trilostane also increased MMP-2. Exogenous P4 with trilostane repressed MMP-2 and restored FM strength. Conclusion: GM-CSF induced P4 production by FM and trophoblastic cells suggesting that locally produced P4 is increased by factors that weaken FM. Inhibition of local P4 production or action resulted in FM weakening with concomitant MMP-2 induction suggesting local P4 maintains FM structural integrity. This weakening is reversed by exogenous P4. These data are consistent with a negative-feedback system whereby P4 induced by GM-CSF, the mediator of inflammation-induced FM weakening, counteracts GM-CSF, inhibiting both its production and downstream action with resultant preservation of FM structural integrity.

Introduction: We use an in-vitro human fetal membrane (FM) explant-based model to study inflammation-induced FM weakening, a prerequisite for PPROM. In this system, GMCSF is a critical intermediate, both necessary and sufficient for TNF alpha and thrombin induced FM weakening. alpha-Lipoic-acid (LA) blocks TNF alpha and thrombin, as well as GMCSF-induced weakening. Recently, we reported LA concomitantly blocks GMCSF-induction of MMPs 2, 9 and 10 and inhibition of TIMPs 1-3. The aim of this study was to show that LA blocks GMCSF-induced increases in additional proteases and reductions in additional protease inhibitors. Methods: FM fragments were cultured +/- LA and then +/- GMCSF. In other experiments, weak versus strong, fresh FM were cultured without additions. Fragments were strength tested and media analyzed by multiplex protein ELISA for proteases and protease inhibitors. Results: GMCSF induced FM weakening and concomitantly increased several Proteases (Cathepsin-S, Proteinase-3, Elastase-2) and decreased several protease inhibitors (NGAL, Cystatin-C, HE4 and Thrombospondin1). LA inhibited GMCSF-induced FM weakening and all enzymatic changes. Untreated weaker versus stronger regions of fresh FM showed comparable differences in proteases and protease inhibitor patterns to GMCSF-stimulated versus controls. Conclusion: LA blocks GMCSF-induced human FM weakening and associated protease increases and inhibitor decreases. The GMCSF-induced spectrum of protease/protease-inhibitor changes is similar to that in the natural weak FM fragments. In concert with previously reported GMCSF-induced changes in MMPs & TIMPs, these other protease and protease-inhibitor changes presumably facilitate FM weakening and rupture. LA blocks these GMCSF effects and therefore may be a useful agent to prevent PPROM.

OBJECTIVE: To evaluate whether labor is associated with lower odds of respiratory morbidity among neonates born from 36 to 40 weeks of gestation and to assess whether this association varies by gestational age and maternal diabetic status. METHODS: We conducted a secondary analysis of women in the Assessment of Perinatal Excellence obstetric cohort who delivered across 25 U.S. hospitals over a 3-year period. Women with a singleton liveborn non-anomalous neonate who delivered from 36 to 40 weeks of gestation were included in our analysis. Those who received antenatal corticosteroids, underwent amniocentesis for fetal lung maturity, or did not meet dating criteria were excluded. Our primary outcome was composite neonatal respiratory morbidity, which included respiratory distress syndrome, ventilator support, continuous positive airway pressure, or neonatal death. Maternal characteristics and neonatal outcomes between women who labored and those who did not were compared. Multivariable logistic regression models were used to evaluate the association between labor and the primary outcome. Interactions between labor and diabetes mellitus and labor and gestational age were tested. RESULTS: Our analysis included 63,187 women who underwent labor and 10,629 who did not. There was no interaction between labor and diabetes mellitus (P=.90). However, there was a significant interaction between labor and gestational age (P=.01). In the adjusted model, labor was associated with lower odds of neonatal respiratory morbidity compared with no labor for neonates delivered from 36-39 weeks of gestation. A 1-week increase in gestational age was associated with a 1.2 times increase in the adjusted odds ratio for the neonatal outcome comparing labor and no labor. CONCLUSION: Labor was associated with lower odds of the composite outcome among neonates delivered from 36-39 weeks of gestation. The magnitude of this association varied by gestational age. The association was similar for women with or without diabetes mellitus.

IMPORTANCE Administration of corticosteroids to women at high risk for delivery in the late preterm period (34-36 weeks' gestation) improves short-term neonatal outcomes. The cost implications of this intervention are not known. OBJECTIVE To compare the cost-effectiveness of treatment with antenatal corticosteroids with no treatment for women at risk for late preterm delivery. DESIGN, SETTING, AND PARTICIPANTS This secondary analysis of the Antenatal Late Preterm Steroids trial, a multicenter randomized clinical trial of antenatal corticosteroids vs placebo in women at risk for late preterm delivery conducted from October 30, 2010, to February 27, 2015. took a third-party payer perspective. Maternal costs were based on Medicaid rates and included those of betamethasone, as well as the outpatient visits or inpatient stay required to administer betamethasone. All direct medical costs for newborn care were included. For infants admitted to the neonatal intensive care unit, comprehensive daily costs were stratified by the acuity of respiratory illness. For infants admitted to the regular newborn nursery, nationally representative cost estimates from the literature were used. Effectiveness was measured as the proportion of infants without the primary outcome of the study: a composite of treatment in the first 72 hours of continuous positive airway pressure or high-flow nasal cannula for 2 hours or more, supplemental oxygen with a fraction of inspired oxygen of 30% or more for 4 hours or more, and extracorporeal membrane oxygenation or mechanical ventilation. This secondary analysis was initially started in June 2016 and revision of the analysis began in May 2017. EXPOSURES Betamethasone treatment. MAIN OUTCOMES AND MEASURES Incremental cost-effectiveness ratio. RESULTS Costs were determined for 1426 mother-infant pairs in the betamethasone group (mean [SD] maternal age, 28.6 [6.3] years; 827 [58.0%] white) and 1395 mother-infant pairs in the placebo group (mean [SD] maternal age, 27.9 [6.2] years; 794 [56.9%] white). Treatment with betamethasone was associated with a total mean (SD) woman-infant-pair cost of $4681($5798), which was significantly less than the mean (SD) amount of $5379 ($8422) for women and infants in the placebo group (difference, $698; 95% CI, $186-$1257; P =.02). The Antenatal Late Preterm Steroids trial determined that betamethasone use is effective: respiratory morbidity decreased by 2.9% (95% CI,-0.5% to-5.4%). Thus, the cost-effectiveness ratio was-$23 986 per case of respiratory morbidity averted. Inspection of the bootstrap replications confirmed that treatment was the dominant strategy in 5000 samples (98.8%). Sensitivity analyses showed that these results held under most assumptions. CONCLUSIONS AND RELEVANCE The findings suggest that antenatal betamethasone treatment is associated with a statistically significant decrease in health care costs and with improved outcomes; thus, this treatment may be an economically desirable strategy.

Objective: To determine the association of maternal glycemia with childhood obesity and metabolic dysfunction. Study design: Secondary analysis of follow-up data 5?10?years after a mild gestational diabetes mellitus (GDM) treatment trial. The relationship between maternal oral glucose tolerance testing (OGTT) at 24?31-week gestation and body mass index (BMI), fasting glucose, insulin, and anthropometric measurements (sum of skinfolds, subscapular/triceps ratio, and waist circumference) in the offspring of untreated mild GDM and non-GDM (abnormal 50-g screen/normal OGTT) women was assessed. Multivariable regression modeling controlling for maternal and neonatal characteristics was employed. Results: A cohort of 236 untreated mild GDM and 480 non-GDM offspring were analyzed. In the combined cohort, significant correlations existed between fasting, 1, 2, and 3?h maternal glucose and subscapular/triceps ratio (all p?<?.04) and in all OGTT values other than the 2-hour value for homeostatic model assessment-estimated insulin resistance (HOMA-IR) (all p?<?.04) and sum of skinfold measurements (all p?<?.03). No correlation was found between OGTT values and childhood BMI Z-score. Multivariable regression modeling showed that OGTT values were associated with only sum of skinfolds and subscapular/triceps ratio and not with childhood BMI Z-score. Hispanic ethnicity and prepregnancy maternal BMI were most consistently related to childhood BMI Z-score and HOMA-IR, and Hispanic ethnicity with fasting glucose. Conclusions: Among women with untreated mild GDM and those without GDM, maternal glycemia is associated with childhood anthropometric measures of obesity but not childhood BMI, fasting glucose, or insulin resistance. Hispanic ethnicity, maternal BMI, and gestational weight gain were consistently related to childhood BMI.

Preeclampsia complicates 5 to 8% of all deliveries. Standard treatment consists of management of hypertension, delivery, and administration of intravenous magnesium sulfate for 24 hours. Recently there has been interest in shortening the time for magnesium therapy in women at low risk of developing preeclampsia, in order to shorten the stay in the labor and delivery unit, decrease costs, and minimize the duration of magnesium-associated symptoms. The investigators prospectively compared the treatment of mild preeclampsia for 12 hours to treatment for 24 hours. Study patients were 34 weeks' gestation or more and had mild preeclampsia as defined by new onset blood pressure of 140 mm Hg or greater systolic and 90 mm Hg or greater diastolic, at least 1+ proteinuria, and the absence of symptoms or laboratory findings consistent with severe preeclampsia. The diagnosis was made either before or within two hours after delivery, before discharge from the labor and delivery unit. Magnesium sulfate was given as a 4 gram IV bolus followed by an infusion of 2 grams per hour, and IV fluids were maintained at a total rate of 125 ml per hour. Randomization was by computer-generated random number table distributed in blocks of 10. Study patients who were clinically stable at the end of their prescribed MgSO4 infusion were sent to the postpartum ward, while those with continued hypertension or symptoms remained on labor and delivery for additional MgSO4 therapy. Of a total of 322 patients with suspected mild preeclampsia, 204 were eligible and 200 were enrolled. Four patients were lost to follow up. The groups receiving either 12 or 24 hours of MGSO4 were similar in terms of the severity of their preeclampsia and history of chronic hypertension or diabetes. One patient in the 24 hour group required additional MgSO4 therapy. Seven in the 12 hour group required additional therapy, and 3 of these had chronic hypertension, three had diabetes, and two had both. Both groups tolerated the MgSO4 well, and no patients experienced seizures or toxicity. The length of the postpartum stay was the same in both groups. These data indicate that selected women with mild preeclampsia can safely receive 12 hours of IV MgSO4 therapy instead of 24 hours. Women with chronic hypertension or diabetes require 24 hours of therapy.