Maternal psychiatric disease and epigenetic evidence suggest a common biology for poor fetal growth.
Maternal psychiatric disease and epigenetic evidence suggest a common biology for poor fetal growth.
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DOI：
10.1186/s12884-015-0627-8
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发表时间：
2015-08-25
影响因子：
3.1
通讯作者：
Williams SM
中科院分区：
文献类型：
--
作者：
Ciesielski TH;Marsit CJ;Williams SM
我们试图在从围产期病历中提取的变量中识别和描述胎儿生长不良的预测因子，以深入了解潜在的病因机制。在这个过程中，我们重新评估了以前观察到的胎儿生长不良和母亲精神疾病之间的联系。我们评估了2008年9月至2010年9月在罗得岛普罗维登斯妇女和婴儿医院分娩的449例妊娠>36周的分娩。本研究组中，胎龄小于（SGA）婴儿的样本过多，排除了胎龄大于（LGA）婴儿的样本。我们评估了记录的临床变量与胎儿生长受损之间的关系：SGA或宫内生长受限（IUGR）诊断。在验证了先前观察到的母体精神疾病和胎儿生长受损之间的关联后，我们通过明确考虑抗抑郁药的使用和妊娠相关症状的时间来解决先前研究中的弱点。然后，我们从这些分娩的一个子集（n = 197）中评估了胎盘中27个候选位点的DNA甲基化水平，以检查表观遗传变异是否可以深入了解导致这种共病的机制。母亲患有产前精神疾病（抑郁、焦虑、强迫症/惊恐）的婴儿，其胎儿生长不良的几率增加（OR调整= 3.36，95%CI：1.38-8.14）。这种关系在接受抗抑郁药治疗的患者（OR调整= 3.69，95%CI：1.31-10.45）和未接受抗抑郁药治疗的患者（OR调整= 3.19，95%CI：1.30-7.83）中相似。在有精神病史但妊娠期无活动性疾病的患者中，OR调整值为0.45（95%CI：0.09-2.35）。瘦素受体转录起始位点附近的一个位点（cg 21655790）在以下情况下甲基化水平降低：1）SGA/IUGR，2）活动性但未消退的精神疾病（未服用抗抑郁药的母亲）。这些结果验证并进一步描述了母体精神疾病与胎儿生长不良之间的关系。由于这种关联似乎依赖于活动性精神疾病，这表明一种短暂的和潜在的可改变的病理生理学。这项研究的分子发现表明，改变瘦素信号可能参与了产前母体精神症状和胎儿生长不良的生物学机制。本文的在线版本（doi：10.1186/s12884-015-0627-8）包含补充材料，可供授权用户使用。
We sought to identify and characterize predictors of poor fetal growth among variables extracted from perinatal medical records to gain insight into potential etiologic mechanisms. In this process we reevaluated a previously observed association between poor fetal growth and maternal psychiatric disease. We evaluated 449 deliveries of >36 weeks gestation that occurred between 9/2008 and 9/2010 at the Women and Infants Hospital in Providence Rhode Island. This study group was oversampled for Small-for-Gestational-Age (SGA) infants and excluded Large-for-Gestational-Age (LGA) infants. We assessed the associations between recorded clinical variables and impaired fetal growth: SGA or Intrauterine Growth Restriction (IUGR) diagnosis. After validating the previously observed association between maternal psychiatric disease and impaired fetal growth we addressed weaknesses in the prior studies by explicitly considering antidepressant use and the timing of symptoms with respect to pregnancy. We then evaluated DNA methylation levels at 27 candidate loci in placenta from a subset of these deliveries (n = 197) to examine if epigenetic variation could provide insight into the mechanisms that cause this co-morbidity. Infants of mothers with prenatal psychiatric disease (Depression, Anxiety, OCD/Panic) had increased odds of poor fetal growth (ORadjusted = 3.36, 95%CI: 1.38-8.14). This relationship was similar among those who were treated with antidepressants (ORadjusted = 3.69, 95%CI: 1.31-10.45) and among those who were not (ORadjusted = 3.19, 95%CI: 1.30-7.83). Among those with a history of psychiatric disease but no active disease in pregnancy the ORadjusted was 0.45 (95%CI: 0.09-2.35). A locus near the transcription start site of the leptin receptor (cg21655790) had methylation levels that were decreased in the presence of: 1) SGA/IUGR, and 2) active but not resolved psychiatric disease (among mothers not on antidepressants). These results validate and further characterize the association between maternal psychiatric disease and poor fetal growth. Because the association appears to depend on active psychiatric disease, this suggests a transient and potentially modifiable pathophysiology. The molecular findings in this study suggest that altered leptin signaling may be involved in the biological mechanisms that link prenatal maternal psychiatric symptoms and poor fetal growth. The online version of this article (doi:10.1186/s12884-015-0627-8) contains supplementary material, which is available to authorized users.