Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.

BackgroundPreterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition.MethodsSamples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes.ResultsThe largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5'and 3' UTR regions.ConclusionsThe results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection

Pregnancy-Associated Hypertension in Glucose-Intolerant Pregnancy and Subsequent Metabolic Syndrome

To evaluate whether pregnancy-associated hypertension (preeclampsia or gestational hypertension), among women with varying degrees of glucose intolerance during pregnancy is associated with maternal metabolic syndrome 5-10 years later

Mild Gestational Diabetes Mellitus and Long-Term Child Health

OBJECTIVETo evaluate whether treatment of mild gestational diabetes mellitus (GDM) confers sustained offspring health benefits, including a lower frequency of obesity.RESEARCH DESIGN AND METHODSFollow-up study of children (ages 5–10) of women enrolled in a multicenter trial of treatment versus no treatment of mild GDM. Height, weight, blood pressure, waist circumference, fasting glucose, fasting insulin, triglycerides, and HDL cholesterol were measured.RESULTSFive hundred of 905 eligible offspring (55%) were enrolled. Maternal baseline characteristics were similar between the follow-up treated and untreated groups. The frequencies of BMI ≥95th (20.8% and 22.9%) and 85th (32.6% and 38.6%) percentiles were not significantly different in treated versus untreated offspring (P = 0.69 and P = 0.26). No associations were observed for BMI z score, log waist circumference, log triglycerides, HDL cholesterol, blood pressure, or log HOMA-estimated insulin resistance (HOMA-IR). The effect of treatment was different by sex for fasting glucose and log HOMA-IR (P for interaction = 0.002 and 0.02, respectively) but not by age-group (5–6 and 7–10 years) for any outcomes. Female offspring of treated women had significantly lower fasting glucose levels.CONCLUSIONSAlthough treatment for mild GDM has been associated with neonatal benefits, no reduction in childhood obesity or metabolic dysfunction in the offspring of treated women was found. However, only female offspring of women treated for mild GDM had lower fasting glucose

Is low-dose aspirin therapy to prevent preeclampsia more efficacious in non-obese women or when initiated early in pregnancy?

<div><p></p><p><i>Objective</i>: Late timing of intervention and maternal obesity are potential explanations for the modest effect of aspirin for preeclampsia prevention. We explored whether low-dose aspirin (LDA) is more effective in women at increased risk when initiated before 16 weeks' gestation or given to non-obese women.</p><p><i>Methods</i>: Secondary analysis of a trial to evaluate LDA (60 mg/d) for preeclampsia prevention in high-risk women. Participants were randomized to LDA or placebo between 13 and 26 weeks. We stratified the effect of LDA on preeclampsia by (a) timing of randomization (< 16 or ≥ 16 weeks gestation) and (b) body mass index (BMI) class (non-obese and obese). The Breslow–Day test for homogeneity was used to assess for variations in effect of LDA across gestational age and BMI groups.</p><p><i>Results</i>: Of 2503 women, 461 (18.4%) initiated LDA < 16 weeks. LDA effect was not better when initiated < 16 weeks (RR: 0.93, 95% CI: 0.67–1.31) versus ≥ 16 weeks (RR: 0.90, 95% CI: 0.75–1.08), (<i>p</i> value for interaction = 0.87). Similarly, LDA effect was not better in non-obese (RR: 0.91, 95% CI: 0.7–1.13) versus obese women (RR: 0.89, 95% CI: 0.7–1.13), (<i>p</i> value for interaction = 0.85).</p><p><i>Conclusion</i>: LDA for preeclampsia prevention was not more effective when initiated < 16 weeks or used in non-obese women at risk for preeclampsia. No particular subgroup of women was more or less likely to benefit from LDA therapy.</p></div

The Association of Periconception Asthma Medication Discontinuation with Adverse Obstetric Outcomes

OBJECTIVE: This study aimed to investigate asthma medication reduction in the periconceptional period as it relates to asthma status and adverse outcomes in pregnancy. STUDY DESIGN: In a prospective cohort study, self-reported current and past asthma medications were collected and analyzes compared measures of asthma status in women who discontinued asthma medication in the 6 months prior to enrollment ( step-down ) versus those who did not ( no change ). Evaluation of asthma was done at three study visits (one per trimester) and by daily diaries, including measures of lung function (percent predicted forced expiratory volume in 1 and 6 s [%FEV1, %FEV6], peak expiratory flow [%PEF], forced vital capacity [%FVC], FEV1 to FVC ratio [FEV1/FVC]), lung inflammation (fractional exhaled nitric oxide [FeNO], ppb), rate of asthma symptoms (activity limitation, night symptoms, rescue inhaler use, wheeze, shortness of breath, cough, chest tightness, chest pain), and rate of asthma exacerbations. Adverse pregnancy outcomes were also evaluated. Adjusted regression analyses examined whether adverse outcomes differed by periconceptional asthma medication changes. RESULTS: Of 279 participants included in analyses, 135 (48.4%) did not change asthma medication in the periconceptional period, whereas 144 (51.6%) reported a step down in medication. Those in the step-down group were more likely to have milder disease (88 [61.1%] in the step-down vs. 74 [54.8%] in the no change group), exhibited less activity limitation (rate ratio [RR]: 0.68, 95% confidence interval [CI]: 0.47-0.98), and experienced fewer asthma attacks (RR: 0.53, 95% CI: 0.34-0.84) during pregnancy. The step-down group had a nonsignificant increase in overall odds of experiencing an adverse pregnancy outcome (odds ratio: 1.62, 95% CI: 0.97-2.72). CONCLUSION: Over half of women with asthma reduce asthma medication in the periconceptional period. Although these women typically have milder disease, a step down in medication may be associated with an increased risk of adverse pregnancy outcomes. KEY POINTS: · Many women reduce their asthma medication in pregnancy.. · Reduction is more common among those with mild disease.. · Medication reduction may lead to adverse pregnancy outcomes.