Viuff Anne-Cathrine F, Pedersen Lars Henning, Kyng Kasper, Staunstrup Nicklas Heine, Børglum Anders, Henriksen Tine Brink
Perinatal Epidemiology Research Unit, Pediatric Department, Aarhus University Hospital Skejby, Aarhus, Denmark.
Department of Obstetrics and Gynecology, Aarhus University Hospital Skejby, Aarhus, Denmark.
Clin Epigenetics. 2016 Sep 7;8(1):94. doi: 10.1186/s13148-016-0262-x. eCollection 2016.
Epigenetic mechanisms are important for the regulation of gene expression and differentiation in the fetus and the newborn child. Symptoms of maternal depression and antidepressant use affects up to 20 % of pregnant women, and may lead to epigenetic changes with life-long impact on child health. The aim of this review is to investigate whether there is an association between exposure to maternal antidepressants during pregnancy and epigenetic changes in the newborn.
Systematic literature searches were performed in MEDLINE and EMBASE combining MeSH terms covering epigenetic changes, use of antidepressant medication, pregnancy and newborns. A keyword search was also performed. We included studies on pregnant women and their children where there was a history of maternal depressed mood or anxiety, a reported use of antidepressant medication, and measurements of epigenetic changes in umbilical cord blood. Studies using genome-wide or candidate-based epigenetic analyses were included. Citations and references from the included articles were investigated to locate further relevant articles. The completeness of reporting as well as the risk of bias and confounding was assessed.
Six studies were included. They all investigated methylation changes. Genome-wide methylation changes were examined in 184 children and methylation status in specific genes was examined in 96 children exposed to antidepressant medication. Three of the studies found an association between use of antidepressant medication during pregnancy and methylation status at various CpG sites measured in cord blood of the newborn. One of these studies found an association in African-Americans, but not Caucasians. The remaining three studies found associations between maternal mood and epigenetic changes in umbilical cord blood but no association between epigenetic changes and maternal use of antidepressant medication.
The included studies have not established a clear association between use of antidepressant medication during pregnancy and epigenetic changes in the cord blood. Future studies using newer, more wide-ranging epigenetic methods could discover possible new differentially methylated sites. Larger sample sizes and good validity of exposures are warranted in order to adjust for level of maternal depression, other maternal illness, maternal use of other types of medication, and maternal ethnicity. PROSPERO registration number: CRD42015026575.
表观遗传机制对于胎儿和新生儿的基因表达调控及分化至关重要。孕期母亲抑郁症状及抗抑郁药使用影响高达20%的孕妇，并可能导致表观遗传变化，对儿童健康产生终生影响。本综述旨在研究孕期母亲使用抗抑郁药与新生儿表观遗传变化之间是否存在关联。
在MEDLINE和EMBASE中进行系统文献检索，结合涵盖表观遗传变化、抗抑郁药物使用、妊娠和新生儿的医学主题词。还进行了关键词搜索。我们纳入了关于孕妇及其子女的研究，这些研究中母亲有情绪低落或焦虑史、报告使用过抗抑郁药物，并且对脐带血中的表观遗传变化进行了测量。纳入了使用全基因组或基于候选基因的表观遗传分析的研究。对纳入文章的参考文献进行调查以查找更多相关文章。评估报告的完整性以及偏倚和混杂风险。
纳入了六项研究。它们均调查了甲基化变化。对184名儿童进行了全基因组甲基化变化检测，对96名暴露于抗抑郁药物的儿童检测了特定基因的甲基化状态。其中三项研究发现孕期使用抗抑郁药物与新生儿脐带血中测量的多个CpG位点的甲基化状态之间存在关联。其中一项研究在非裔美国人中发现了关联，但在白种人中未发现。其余三项研究发现母亲情绪与脐带血表观遗传变化之间存在关联，但表观遗传变化与母亲使用抗抑郁药物之间无关联。
纳入的研究尚未确定孕期使用抗抑郁药物与脐带血表观遗传变化之间存在明确关联。未来使用更新的、更广泛的表观遗传方法的研究可能会发现新的差异甲基化位点。为了调整母亲抑郁程度、其他母亲疾病、母亲使用其他类型药物以及母亲种族等因素，需要更大的样本量和良好的暴露有效性。PROSPERO注册号：CRD42015026575。
