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PurposeAltered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory regions has previously been associated with obesity, and several malignancies including colon, esophageal, and prostate adenocarcinomas, presumably via changes in expression and/or loss of imprinting, but the functional significance of these DNA methylation marks have not been demonstrated in humans. We examined associations among DNA methylation at IGF2 differentially methylated regions (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and birth weight in newborns.MethodsQuestionnaire data were obtained from 300 pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were measured by ELISA assays. Generalized linear regression models were used to examine the relationship between DMR methylation and IGF2 levels.ResultsLower IGF2 DMR methylation was associated with elevated plasma IGF2 protein concentrations (β = −9.87, p < 0.01); an association that was stronger in infants born to obese women (pre-pregnancy BMI > 30 kg/m2, β = −20.21, p < 0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI, cigarette smoking, gestational diabetes, and infant sex. These patterns of association were not apparent at the H19 DMR.ConclusionOur data suggest that variation in IGF2 DMR methylation is an important mechanism by which circulating IGF2 concentrations, a putative risk factor for obesity and cancers of the colon, esophagus, and prostate, are modulated; associations that may depend on pre-pregnancy obesity.

ObjectiveBacterial colonization of the fetal membranes and its role in pathogenesis of membrane rupture is poorly understood. Prior retrospective work revealed chorion layer thinning in preterm premature rupture of membranes (PPROM) subjects. Our objective was to prospectively examine fetal membrane chorion thinning and to correlate to bacterial presence in PPROM, preterm, and term subjects.Study DesignPaired membrane samples (membrane rupture and membrane distant) were prospectively collected from: PPROM = 14, preterm labor (PTL = 8), preterm no labor (PTNL = 8), term labor (TL = 10), and term no labor (TNL = 8), subjects. Sections were probed with cytokeratin to identify fetal trophoblast layer of the chorion using immunohistochemistry. Fluorescence in situ hybridization was performed using broad range 16 s ribosomal RNA probe. Images were evaluated, chorion and choriodecidua were measured, and bacterial fluorescence scored. Chorion thinning and bacterial presence were compared among and between groups using Student's t-test, linear mixed effect model, and Poisson regression model (SAS Cary, NC).ResultsIn all groups, the fetal chorion cellular layer was thinner at rupture compared to distant site (147.2 vs. 253.7 µm, p<0.0001). Further, chorion thinning was greatest among PPROM subjects compared to all other groups combined, regardless of site sampled [PPROM(114.9) vs. PTL(246.0) vs. PTNL(200.8) vs. TL(217.9) vs. TNL(246.5)]. Bacteria counts were highest among PPROM subjects compared to all other groups regardless of site sampled or histologic infection [PPROM(31) vs. PTL(9) vs. PTNL(7) vs. TL(7) vs. TNL(6)]. Among all subjects at both sites, bacterial counts were inversely correlated with chorion thinning, even excluding histologic chorioamnionitis (p<0.0001 and p = 0.05).ConclusionsFetal chorion was uniformly thinner at rupture site compared to distant sites. In PPROM fetal chorion, we demonstrated pronounced global thinning. Although cause or consequence is uncertain, bacterial presence is greatest and inversely correlated with chorion thinning among PPROM subjects.

Maternal immunization is an effective strategy to prevent and/or minimize the severity of infectious diseases in pregnant women and their infants. Based on the success of vaccination programs to prevent maternal and neonatal tetanus, maternal immunization has been well received in the United States and globally as a promising strategy for the prevention of other vaccine-preventable diseases that threaten pregnant women and infants, such as influenza and pertussis. Given the promise for reducing the burden of infectious conditions of perinatal significance through the development of vaccines against relevant pathogens, the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) sponsored a series of meetings to foster progress toward clinical development of vaccines for use in pregnancy. A multidisciplinary group of stakeholders convened at the NIH in December 2013 to identify potential barriers and opportunities for scientific advancement in maternal immunization.

Tdap was well-tolerated in pregnant and nonpregnant women. Pregnant women were more likely to report moderate/severe pain at the Tdap injection-site compared with nonpregnant women, but did not necessitate medical visits. Prior Tdap receipt did not increase occurrence of moderate/severe local or systemic reactions in pregnant women. Serologic responses to all vaccine antigens were robust. Clinical Trial Registration@ClinicalTrials.gov. NCT02209623. https://clinicaltrials.gov/ct2/show/NCT02209623.

Background Little is known of the burden of Group B Streptococcus (GBS) colonization among pregnant women in Jordan. We conducted a pilot study to determine the prevalence of GBS among pregnant women in Amman, Jordan, where GBS testing is not routine. We also explored GBS serotypes and the performance of a rapid GBS antigen diagnostic test. Methods We collected vaginal-rectal swabs from women who presented for labor and delivery at Al-Bashir Hospital. Three methods were used to identify GBS: Strep B Rapid Test (Creative Diagnostics), blood agar media (Remel) with confirmed with BBL Streptocard acid latex test (Becton Dickinson), and CHROMagar StrepB (Remel). Results were read by a senior microbiologist. We defined our gold standard for GBS-positive as a positive blood agar culture confirmed by latex agglutination and positive CHROMagar. PCR testing determined serotype information. Demographic and clinical data were also collected. Results In April and May 2015, 200 women were enrolled with a median age of 27 years (IQR: 23–32); 89.0% were Jordanian nationals and 71.9% completed secondary school. Median gestational age was 38 weeks (IQR: 37–40); most women reported prenatal care (median 9 visits; IQR: 8–12). Median parity was 2 births (IQR: 1–3). Pre-pregnancy median BMI was 24.1 (IQR: 21.5–28.0) and 14.5% reported an underlying medical condition. Obstetric complications included gestational hypertension (9.5%), gestational diabetes (6.0%), and UTI (53.5%), of which 84.5% reported treatment. Overall, 39 (19.5%) of women were GBS-positive on blood agar media and CHROMagar, while 67 (33.5%) were positive by rapid test (36% sensitivity, 67% specificity). Serotype information was available for 25 (64%) isolates: III (48%), Ia (24%), II (20%), and V (8%). No demographic or clinical differences were noted between GBS+ and GBS-negative women. Conclusions Nearly one in five women presenting for labor in Jordan was colonized with GBS, with serotype group III as the most common. The rapid GBS antigen diagnostic had low sensitivity and specificity. These results support expanded research in the region, including defining GBS resistance patterns, serotyping information, and risk factors. It also emphasizes the need for routine GBS testing and improved rapid GBS diagnostics for developing world settings.

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OBJECTIVES:To compare head circumference (HC) in neonates treated for neonatal abstinence syndrome (NAS) with control neonates without antenatal opioid exposure. METHODS:Our prospective cohort study ran from April 1, 2014, through December 31, 2016. Newborns treated for NAS delivered from well-dated pregnancies ≥34 weeks' gestation were compared with newborns who were nonopioid exposed and matched for race, parity, mode of delivery, and gestational age. All mothers underwent serial antenatal urine drug testing. A minimum of 754 study participants were needed (377 in each group) to demonstrate an increase in the proportion of newborns with HCs less than or equal to the 10th percentile from 10% in controls to a minimum of 20% in NAS newborns with 90% power. RESULTS:A total of 858 neonates were enrolled (429 NAS cases and 429 controls). Mean HC for cases was 33.04 cm (±1.9 cm) compared with 33.99 cm (±2.0 cm) for controls (P < .0001). Among the 429 NAS cases, the mothers of 372 (87%) were on opioid medicationassisted treatment. For NAS cases, 30.1% (95% confidence interval: 25.8%-34.7%) had an HC less than or equal to the 10th percentile (129 of 429 neonates), and 8.2% (95% confidence interval: 5.8%-11.2%) had an HC less than or equal to the third percentile (35 of 429 neonates). Multivariate analysis was used and determined that only chronic opioid use during gestation resulting in a neonate who was NAS treated was a significant risk factor for the observed smaller HC. CONCLUSIONS: Chronic opioid use during pregnancy sufficient to cause NAS was associated with smaller HCs at birth. Most mothers were on opioid agonist medication-assisted treatment, which is currently the recommended treatment option during pregnancy.