4 research outputs found

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

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    <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

    Maternal tobacco use modestly alters correlated epigenome-wide placental DNA methylation and gene expression

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    Several studies linking alterations in differential placental methylation with pregnancy disorders have implicated (de) regulation of the placental epigenome with fetal programming and later-in-life disease. We have previously demonstrated that maternal tobacco use is associated with alterations in promoter methylation of placental CYP1A1 and that these changes are correlated with CYP1A1 gene expression and fetal growth restriction. In this study we sought to expand our analysis of promoter methylation by correlating it to gene expression on a genome-wide scale. Employing side-by-side IlluminaHG-12 gene transcription with Infinium27K methylation arrays, we interrogated correlative changes in placental gene expression and DNA methylation associated with maternal tobacco smoke exposure at an epigenome-wide level and in consideration of signature gene pathways. We observed that the expression of 623 genes and the methylation of 1,024 CpG dinucleotides are significantly altered among smokers, with only 38 CpGs showing significant differential methylation (differing by a methylation level of ≥10%). We identified a significant Pearson correlation (≥0.7 or ≤-0.7) between placental transcriptional regulation and differential CpG methylation in only 25 genes among non-smokers but in 438 genes among smokers (18-fold increase, p < 0.0001), with a dominant effect among oxidative stress pathways. Differential methylation at as few as 6 sites was attributed to maternal smoking-mediated birth weight reduction in linear regression models with Bonferroni correction (p < 1.8 × 10−6). These studies suggest that a common perinatal exposure (such as maternal smoking) deregulates placental methylation in a CpG site-specific manner that correlates with meaningful alterations in gene expression along signature pathways
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