Placental Accelerated Aging in Antenatal Depression.

BACKGROUND: Antenatal maternal depression is associated with poor pregnancy outcomes and long-term effects on 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. It is possible that the relationship between antenatal depression and poor pregnancy outcomes is partly mediated via placental aging.

CONCLUSION: Antenatal depressive symptoms during second trimester was associated with an average of 0.41 weeks increased placental age acceleration. Accelerated placental aging may play important role in underlying mechanism linking antenatal depression to pregnancy complications related to placental dysfunction. Copyright © 2023. Published by Elsevier Inc.

OBJECTIVE: 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.

RESULTS: There were 31 (10.3%) women with depressive symptoms (i.e., EDPS score >=10) in first trimester, 48 (16%) in second trimester, and 49 (16.4%) in third trimester. Of these, 21 (7.2%) women 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 second trimester had 0.41 weeks higher placental age acceleration compared to women without depressive symptoms during second trimester (beta=0.21 weeks, 95% CI [-0.17, 0.58], P=.28 during 1st trimester; beta=0.41 weeks, 95% CI [0.10, 0.71], P=.009 during 2nd trimester; beta=0.17 weeks, 95% CI [-0.14, 0.47], P=.29 during 3rd trimester). Sustained first and second trimester depressive symptoms were associated with 0.72 weeks higher placental age acceleration (95% CI [0.29, 1.15], P=.001) compared to no depressive symptoms in the two trimesters. The association between second trimester depressive symptoms and higher placental epigenetic age acceleration strengthened in analysis of pregnancies with male fetuses (beta=0.53 weeks, 95% CI [0.06, 1.08], P=.03) but was not significant in pregnancies with female fetuses.

STUDY DESIGN: The study included 301 women who provided placenta samples at delivery as part of the NICHD Fetal Growth Studies - Singletons that recruited participants from diverse race/ethnic groups at 12 U.S. clinical sites (2009 - 2013). Women underwent depression screening using the Edinburgh Postnatal Depression Scale up to 6 times across the three trimesters of pregnancy. Depressive symptoms status was determined for each pregnancy trimester using an Edinburgh Postnatal Depression Scale score, in which a score >=10 was defined as having depressive symptoms and <10 as not depressed. 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 EDPS score >=10 compared with <10 in the first, second, and third trimester (i.e., depressive symptoms compared to none in each trimester) and placental age acceleration were tested using multivariable linear regression adjusting for maternal age, parity, race/ethnicity, and employment.

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