Application of 4-way decomposition to the analysis of placental-fetal biomarkers as intermediary variables between maternal body mass index and birthweight.
Application of 4-way decomposition to the analysis of placental-fetal biomarkers as intermediary variables between maternal body mass index and birthweight.
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DOI：
10.3389/frph.2022.994436
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发表时间：
2022
影响因子：
--
通讯作者：
Adibi, Jennifer J. J.
中科院分区：
文献类型：
--
作者：
Xun, Xiaoshuang;Qin, Xu;Layden, Alexander J. J.;Yin, Qing;Swan, Shanna H. H.;Barrett, Emily S. S.;Bush, Nicole R. R.;Sathyanarayana, Sheela;Adibi, Jennifer J. J.
人绒毛膜促性腺激素(HCG)是孕期测量的一种胎盘激素，用于预测个体水平、胎儿非整倍体和其他并发症的风险；但也可能有助于更广泛地了解儿童发育的胎盘起源。绒毛膜促性腺激素与母亲体重指数(BMI)和新生儿体重有关。本研究的主要目的是通过因果中介分析评价hCG作为母体体重指数对新生儿出生体重影响的中介因子。研究对象是来自3个美国网站的356名女性(2010-2013年)。采用MED4WAY四方分解法(STATA)筛选孕期母亲BMI对新生儿出生体重的总效应、直接效应、hCG中介效应、BMI与hCG相加交互作用和相加交互作用的中介作用。评估了胎儿性别对效果的影响，并进行了敏感性分析以评估未测量混杂的假设。分析其他胎盘-胎儿生物标志物[妊娠相关血浆蛋白A(PAPPA)、中期妊娠hCG、抑制素-A、雌三醇、甲胎蛋白]进行比较。在妊娠早期，母亲体重指数第75百分位数与第25百分位数的出生体重标准差增加了0.20(95%可信区间0.04，0.36)。一旦分层，直接影响关联在怀有女性的女性中为零。在怀有男性的女性中，hCG没有调节这种关系。在妊娠女性孕妇中，hCG对出生体重的影响存在反向中介效应(−0.0 6，95%CI：−0.12，0.0 1)和正向交互作用(0.0 6，95%CI 0.0 0，0.13)。在怀有男性的女性中，母亲体重指数对出生体重的影响被PAPPA逆转(−0.09，95%CI：−0.17，0.00)。针对性别的调解主要出现在妊娠的前三个月。中期妊娠甲胎蛋白仅对男婴的母体体重指数效应有正向调节作用(0.0 6，95%CI：−0.0 1，0.13)。由于未测量的混杂因素，效应估计对潜在的偏差是稳健的。这些发现促使研究人员在量化母亲肥胖对胎儿生长的影响时，考虑妊娠早期胎盘生物标记物和性别特异性机制。
Human chorionic gonadotropin (hCG) is a placental hormone measured in pregnancy to predict individual level risk of fetal aneuploidy and other complications; yet may be useful in understanding placental origins of child development more generally. hCG was associated with maternal body mass index (BMI) and with birthweight. The primary aim here was to evaluate hCG as a mediator of maternal BMI effects on birthweight by causal mediation analysis. Subjects were 356 women from 3 U.S. sites (2010–2013). The 4-way decomposition method using med4way (STATA) was applied to screen for 5 types of effects of first trimester maternal BMI on birthweight: the total effect, the direct effect, mediation by hCG, additive interaction of BMI and hCG, and mediation in the presence of an additive interaction. Effect modification by fetal sex was evaluated, and a sensitivity analysis was performed to evaluate the assumption of unmeasured confounding. Additional placental-fetal biomarkers [pregnancy associated plasma protein A (PAPPA), second trimester hCG, inhibin-A, estriol, alpha fetoprotein] were analyzed for comparison. For first trimester hCG, there was a 0.20 standard deviation increase in birthweight at the 75th vs. 25th percentile of maternal BMI (95% CI 0.04, 0.36). Once stratified, the direct effect association was null in women carrying females. In women carrying males, hCG did not mediate the relationship. In women carrying females, there was a mediated effect of maternal BMI on birthweight by hCG in the reverse direction (−0.06, 95% CI: −0.12, 0.01), and a mediated interaction in the positive direction (0.06, 95% CI 0.00, 0.13). In women carrying males, the maternal BMI effect on birthweight was reverse mediated by PAPPA (−0.09, 95% CI: −0.17, 0.00). Sex-specific mediation was mostly present in the first trimester. Second trimester AFP was a positive mediator of maternal BMI effects in male infants only (0.06, 95% CI: −0.01, 0.13). Effect estimates were robust to potential bias due to unmeasured confounders. These findings motivate research to consider first trimester placental biomarkers and sex-specific mechanisms when quantifying the effects of maternal adiposity on fetal growth.
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影响因子：
7
作者：
Imai, Kosuke;Keele, Luke;Tingley, Dustin
通讯作者：
Tingley, Dustin
影响因子：
6.7
作者：
Eskild, Anne;Fedorcsak, Peter;Tanbo, Tom G.
通讯作者：
Tanbo, Tom G.
DOI：
10.1016/0002-9378(82)90474-4
发表时间：
1982-01-01
影响因子：
9.8
作者：
FURUHASHI, N;SUZUKI, M;TAKAHASHI, T
通讯作者：
TAKAHASHI, T
影响因子：
2.4
作者：
Hong, Guanglei;Qin, Xu;Yang, Fan
通讯作者：
Yang, Fan
影响因子：
4.1
作者：
Adibi JJ;Xun X;Zhao Y;Yin Q;LeWinn K;Bush NR;Panigrahy A;Peddada S;Alfthan H;Stenman UH;Tylavsky F;Koistinen H
通讯作者：
Koistinen H