National Human Genome Research Institute, National Institutes of Health, Bethesda, MD (Dr Saeed); Department of Maternal-Fetal Medicine, Medstar Washington Hospital Center, Washington, DC (Drs Saeed).
Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (Drs Wu, Grantz, and Tekola-Ayele).
Am J Obstet Gynecol MFM. 2024 Jan;6(1):101237. doi: 10.1016/j.ajogmf.2023.101237. Epub 2023 Nov 25.
Antenatal maternal depression is associated with poor pregnancy outcomes and long-term effects on the offspring. Previous studies have identified links between antenatal depression and placental DNA methylation and between placental epigenetic aging and poor pregnancy outcomes, such as preterm labor and preeclampsia. The relationship between antenatal depression and poor pregnancy outcomes may be partly mediated via placental aging.
This study aimed to investigate whether antenatal depressive symptoms are associated with placental epigenetic age acceleration, an epigenetic aging clock measure derived from the difference between methylation age and gestational age at delivery.
The study included 301 women who provided placenta samples at delivery as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies - Singletons that recruited participants from diverse race and ethnic groups at 12 US clinical sites (2009-2013). Women underwent depression screening using the Edinburgh Postnatal Depression Scale up to 6 times across the 3 trimesters of pregnancy. Depressive symptoms status was determined for each pregnancy trimester using an Edinburgh Postnatal Depression Scale score, in which a score of ≥10 was defined as having depressive symptoms and a score of <10 was defined as not having depressive symptoms. Placental DNA methylation was profiled from placenta samples. Placental epigenetic age was estimated using a methylation-based age estimator (placental "epigenetic clock") that has previously been found to have high placental gestational age prediction accuracy for uncomplicated term pregnancies. Placental age acceleration was defined to be the residual upon regressing the estimated epigenetic age on gestational age at delivery. Associations between an Edinburgh Postnatal Depression Scale score of ≥10 and an Edinburgh Postnatal Depression Scale score of <10 in the first, second, and third trimesters of pregnancy (ie, depressive symptoms vs none in each trimester) and placental age acceleration were tested using multivariable linear regression adjusting for maternal age, parity, race and ethnicity, and employment.
There were 31 (10.3%), 48 (16%), and 49 (16.4%) women with depressive symptoms (ie, Edinburgh Postnatal Depression Scale score of ≥10) in the first, second, and third trimesters of pregnancy, respectively. Of these women, 21 (7.2%) had sustained first- and second-trimester depressive symptoms, 19 (7%) had sustained second- and third-trimester depressive symptoms, and 12 (4.8%) had sustained depressive symptoms throughout pregnancy. Women with depressive symptoms in the second trimester of pregnancy had 0.41 weeks higher placental age acceleration than women without depressive symptoms during the second trimester of pregnancy (β=0.21 weeks [95% confidence interval, -0.17 to 0.58; P=.28] during the first trimester of pregnancy; β=0.41 weeks [95% confidence interval, 0.10-0.71; P=.009] during the second trimester of pregnancy; β=0.17 weeks [95% confidence interval, -0.14 to 0.47; P=.29] during the third trimester of pregnancy). Sustained first- and second-trimester depressive symptoms were associated with 0.72 weeks higher placental age acceleration (95% confidence interval, 0.29-1.15; P=.001) than no depressive symptom in the 2 trimesters. The association between second-trimester depressive symptoms and higher placental epigenetic age acceleration strengthened in the analysis of pregnancies with male fetuses (β=0.53 weeks; 95% confidence interval, 0.06-1.08; P=.03) but was not significant in pregnancies with female fetuses.
Antenatal depressive symptoms during the second trimester of pregnancy were associated with an average of 0.41 weeks of increased placental age acceleration. Accelerated placental aging may play an important role in the underlying mechanism linking antenatal depression to pregnancy complications related to placental dysfunction.
产前产妇抑郁与不良妊娠结局及对子代的长期影响有关。先前的研究已经确定了产前抑郁与胎盘 DNA 甲基化之间的联系，以及胎盘表观遗传衰老与早产和子痫前期等不良妊娠结局之间的联系。产前抑郁与不良妊娠结局之间的关系可能部分通过胎盘老化来介导。
本研究旨在探讨产前抑郁症状是否与胎盘表观遗传年龄加速有关，这是一种从分娩时的甲基化年龄与胎盘年龄的差异中得出的胎盘表观遗传衰老时钟测量方法。
这项研究纳入了 301 名在分娩时提供胎盘样本的女性，这些女性是 Eunice Kennedy Shriver 国家儿童健康与人类发展研究所胎儿生长研究-单胎的一部分，该研究在 12 个美国临床站点招募了来自不同种族和族裔的参与者（2009-2013 年）。女性在妊娠的 3 个 trimester 中通过爱丁堡产后抑郁量表（Edinburgh Postnatal Depression Scale）进行抑郁筛查多达 6 次。使用爱丁堡产后抑郁量表的评分来确定每个妊娠 trimester 的抑郁症状状态，其中评分≥10 定义为有抑郁症状，评分<10 定义为没有抑郁症状。从胎盘样本中分析胎盘 DNA 甲基化。使用基于甲基化的年龄估算器（胎盘“表观遗传时钟”）来估计胎盘的表观遗传年龄，该估算器以前在预测简单足月妊娠的胎盘妊娠年龄方面具有很高的准确性。胎盘年龄加速被定义为在回归估计的表观遗传年龄与分娩时的胎龄后残差。使用多变量线性回归调整母亲年龄、产次、种族和民族以及就业状况，检验第一、二和三 trimester 妊娠时爱丁堡产后抑郁量表评分≥10 与评分<10（即每个 trimester 中均无抑郁症状）与胎盘年龄加速之间的关系。
分别有 31 名（10.3%）、48 名（16%）和 49 名（16.4%）女性在妊娠的第一、二和三 trimester 中出现抑郁症状（即爱丁堡产后抑郁量表评分≥10）。其中，21 名（7.2%）女性在第一和第二 trimester 中持续出现抑郁症状，19 名（7%）女性在第二和第三 trimester 中持续出现抑郁症状，12 名（4.8%）女性在整个妊娠期间持续出现抑郁症状。与妊娠第二 trimester 中没有抑郁症状的女性相比，妊娠第二 trimester 中出现抑郁症状的女性胎盘年龄加速高 0.41 周（β=0.21 周[95%置信区间，-0.17 至 0.58；P=.28]在第一 trimester 妊娠期间；β=0.41 周[95%置信区间，0.10-0.71；P=.009]在第二 trimester 妊娠期间；β=0.17 周[95%置信区间，-0.14 至 0.47；P=.29]在第三 trimester 妊娠期间）。持续存在第一和第二 trimester 的抑郁症状与胎盘年龄加速高 0.72 周相关（95%置信区间，0.29-1.15；P=.001），而在两个 trimester 中没有抑郁症状。第二 trimester 抑郁症状与更高的胎盘表观遗传年龄加速之间的关联在男性胎儿妊娠的分析中得到加强（β=0.53 周；95%置信区间，0.06-1.08；P=.03），但在女性胎儿妊娠中不显著。
妊娠第二 trimester 的产前抑郁症状与平均 0.41 周的胎盘年龄加速有关。加速的胎盘老化可能在产前抑郁与与胎盘功能障碍相关的妊娠并发症之间的潜在机制中发挥重要作用。
