Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.
Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, 230032, Anhui, China.
BMC Pediatr. 2021 Oct 29;21(1):479. doi: 10.1186/s12887-021-02938-z.
We have recently reported that maternal prenatal pregnancy-related anxiety predicts preschoolers' emotional and behavioral development in a gender-dependent manner. This study aims to test for this gender-specific effect in a different cohort and investigate whether the gender difference was specific to placental methylation of genes regulating glucocorticoids.
A total of 2405 mother-child pairs from the Ma'anshan Birth Cohort Study were included in present study. The maternal pregnancy-related anxiety symptoms were evaluated with the Pregnancy-Related Anxiety Questionnaire in the third trimester of pregnancy. Child neurobehavior was assessed with the Strengths and Difficulties Questionnaire at 4 years old. Placental methylation of FKBP5, NR3C1 and HSD11B2 genes was quantified using the MethylTarget approach in 439 pregnant women. After exploratory factor analysis, the associations between methylation factor scores and pregnancy-related anxiety and child neurobehavior were examined using logistic regression analysis.
After controlling for confounding factors, pregnancy-related anxiety in the third trimester of pregnancy increased the risk of hyperactivity only in boys and emotional symptoms only in girls. Decreased scores of the factor characterized by FKBP5 methylation were associated with maternal pregnancy-related anxiety only in boys. Furthermore, increased scores of the factors characterized by NR3C1 and HSD11B2 methylation were associated with hyperactivity (NR3C1: adjusted OR = 1.80, 95%CI = 1.15-2.83) and emotional symptoms (HSD11B2: adjusted OR = 0.53, 95%CI = 0.29-0.97; NR3C1: adjusted OR = 1.64, 95%CI = 1.03-2.59) only in boys. However, the scores of the factor characterized by FKBP5, NR3C1 and HSD11B2 did not mediate the relationship between maternal pregnancy-related anxiety and preschoolers' emotional symptoms and hyperactivity.
Our results suggested that pregnancy-related anxiety in the third trimester of pregnancy predicted preschoolers' emotional symptoms and hyperactivity in a gender-dependent manner. Although we did not find the mediation role of the placental methylation of genes regulating glucocorticoids, we found it was associated with both maternal pregnancy-related anxiety and preschoolers' emotional symptoms and hyperactivity in a gender-dependent manner.
我们最近报道称，孕妇产前与妊娠相关的焦虑以性别依赖的方式预测学龄前儿童的情绪和行为发展。本研究旨在在不同队列中检验这种性别特异性效应，并探讨这种性别差异是否仅存在于调节糖皮质激素的基因的胎盘甲基化。
本研究共纳入了来自马鞍山出生队列研究的 2405 对母婴。在妊娠晚期，采用妊娠相关焦虑问卷评估母亲的妊娠相关焦虑症状。在 4 岁时，采用长处和困难问卷评估儿童神经行为。采用 MethylTarget 方法对 439 名孕妇的 FKBP5、NR3C1 和 HSD11B2 基因的胎盘甲基化进行定量。在进行探索性因子分析后，采用逻辑回归分析检验了甲基化因子评分与妊娠相关焦虑和儿童神经行为之间的关联。
在校正混杂因素后，妊娠晚期的妊娠相关焦虑增加了男孩多动障碍的风险，仅增加了女孩情绪症状的风险。FKBP5 甲基化特征评分的降低仅与男孩的母亲妊娠相关焦虑相关。此外，NR3C1 和 HSD11B2 甲基化特征评分的增加与多动障碍（NR3C1：调整后的 OR=1.80，95%CI=1.15-2.83）和情绪症状（HSD11B2：调整后的 OR=0.53，95%CI=0.29-0.97；NR3C1：调整后的 OR=1.64，95%CI=1.03-2.59）相关，仅与男孩相关。然而，FKBP5、NR3C1 和 HSD11B2 特征评分的因子与母亲妊娠相关焦虑和学龄前儿童的情绪症状和多动障碍之间的关系没有中介作用。
我们的研究结果表明，妊娠晚期的妊娠相关焦虑以性别依赖的方式预测学龄前儿童的情绪症状和多动障碍。虽然我们没有发现调节糖皮质激素的基因的胎盘甲基化具有中介作用，但我们发现它与母亲妊娠相关焦虑和学龄前儿童的情绪症状和多动障碍均相关，且这种关联具有性别依赖性。
