ImportancePrenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined.ObjectiveTo determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations.Design, Setting, and ParticipantsThis was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023.ExposuresLevels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy.Main Outcomes and MeasuresSelf-reported depressive symptoms at adolescent follow-up.ResultsA total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P = .03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75).Conclusions and RelevanceIn this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.

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从产前母体炎症到青少年抑郁症状的性别特异性途径

重要性产前母亲炎症与成年后代的重度抑郁症以及儿童时期的内化和外化症状有关。然而，产前炎症与后代青春期抑郁症之间的关联尚未得到检验。 目的确定妊娠期间母亲的炎症生物标志物水平是否与青少年后代的抑郁症状相关，并研究妊娠时间、后代性别和儿童期之间的关系。精神症状影响这些关联。设计、设置和参与者这是一项针对儿童健康与发展研究 (CHDS) 的基于人群的出生队列的观察性研究，该研究招募了几乎所有接受凯撒基金会健康计划 (KFHP) 产科护理的母亲）于 1959 年 6 月至 1966 年 9 月间在加利福尼亚州阿拉米达县进行。从母亲那里收集妊娠数据和血清，并收集后代儿童时期（9 至 11 岁）和青春期（15 至 17 岁）的精神症状数据。包括在妊娠早期和/或中期具有可用的母亲产前炎症生物标志物的母子二元体以及青少年随访时的后代抑郁症状数据。数据分析于 2020 年 3 月至 2023 年 6 月期间进行。暴露炎症生物标志物（白细胞介素 6 [IL-6]、IL-8、IL-1 受体拮抗剂 [IL-1RA] 和可溶性肿瘤坏死因子受体-II）的水平主要结果和措施青少年随访时自我报告的抑郁症状。结果共有 674 名母亲（平均 [SD] 年龄，28.1 [5.9] 岁）及其后代（350 名男性和325 名女性）被纳入本研究。妊娠中期较高的 IL-6 与后代青春期抑郁症状的加重显着相关（乙, 0.57; 标准误差，0.26）；磷= .03)。有调节的中介分析表明，儿童外化症状显着介导了男性后代妊娠早期 IL-6 与青少年抑郁症状之间的关联。乙, 0.18; 95% CI, 0.02-0.47），而儿童内化症状介导了妊娠中期 IL-1RA 与女性后代青少年抑郁症状之间的关联（乙, 0.80; 95% CI, 0.19-1.75）。结论和相关性在这项研究中，产前母亲炎症与青少年后代的抑郁症状相关。研究结果表明，产前危险因素导致青少年抑郁症状的途径可能因接触产前炎症的时间和后代性别的不同而有所不同。