ABSTRACT

Circulating miRNA may contribute to the development of adverse birth outcomes. However, few studies have investigated extracellular vesicle (EV) miRNA, which play important roles in intercellular communication, or compared miRNA at multiple time points in pregnancy. In the current study, 800 miRNA were profiled for EVs from maternal plasma collected in early (median: 12.5 weeks) and late (median: 31.8 weeks) pregnancy from 156 participants in the MADRES Study, a health disparity pregnancy cohort. Associations between miRNA and birth weight, birth weight for gestational age (GA), and GA at birth were examined using covariate-adjusted robust linear regression. Differences by infant sex and maternal BMI were also investigated. Late pregnancy measures of 13 miRNA were associated with GA at birth (P_FDR<0.050). Negative associations were observed for eight miRNA (miR-4454+ miR-7975, miR-4516, let-7b-5p, miR-126-3p, miR-29b-3p, miR-15a-5p, miR-15b-5p, miR-19b-3p) and positive associations for five miRNA (miR-212-3p, miR-584-5p, miR-608, miR-210-3p, miR-188-5p). Predicted target genes were enriched (P_FDR<0.050) in pathways involved in organogenesis and placental development. An additional miRNA (miR-107), measured in late pregnancy, was positively associated with GA at birth in infants born to obese women (P_FDR for BMI interaction = 0.011). In primary analyses, the associations between early pregnancy miRNA and birth outcomes were not statistically significant (P_FDR≥0.05). However, sex-specific associations were observed for early pregnancy measures of 37 miRNA and GA at birth (P_FDR for interactions<0.050). None of the miRNA were associated with fetal growth measures (P_FDR≥0.050). Our findings suggest that EV miRNA in both early and late pregnancy may influence gestational duration.

摘要

循环 miRNA 可能导致不良出生结局的发生。然而，很少有研究调查在细胞间通讯中发挥重要作用的细胞外囊泡 (EV) miRNA，或比较妊娠多个时间点的 miRNA。在目前的研究中，从健康差异妊娠队列 MADRES 研究的 156 名参与者中收集了孕早期（中位数：12.5 周）和晚期（中位数：31.8 周）的母体血浆中的 800 个 miRNA 进行了 EV 分析。使用协变量调整的稳健线性回归检查 miRNA 与出生体重、胎龄出生体重 (GA) 和出生时 GA 之间的关联。还调查了婴儿性别和母亲 BMI 的差异。13 种 miRNA 的晚期妊娠测量与出生时 GA 相关（P _FDR<0.050)。8 种 miRNA（miR-4454+ miR-7975、miR-4516、let-7b-5p、miR-126-3p、miR-29b-3p、miR-15a-5p、miR-15b-5p、 miR-19b-3p）和五种 miRNA（miR-212-3p、miR-584-5p、miR-608、miR-210-3p、miR-188-5p）的正相关。预测的靶基因在涉及器官发生和胎盘发育的途径中富集（P _{FDR <0.050）。}在妊娠晚期测量的额外 miRNA (miR-107) 与肥胖女性所生婴儿出生时 GA 呈正相关（BMI 交互作用的 P _FDR = 0.011）。在初步分析中，早孕 miRNA 与出生结局之间的关联没有统计学意义（P _FDR≥0.05)。然而，在出生时 37 种 miRNA 和 GA 的早期妊娠测量中观察到性别特异性关联（相互作用的 P _FDR <0.050）。没有一个 miRNA 与胎儿生长测量相关（P _FDR ≥0.050）。我们的研究结果表明，妊娠早期和晚期的 EV miRNA 可能会影响妊娠持续时间。