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炎症的早期起源:一项前瞻性队列研究中对产前和儿童期社会逆境的考察。

Early origins of inflammation: An examination of prenatal and childhood social adversity in a prospective cohort study.

作者信息

Slopen Natalie, Loucks Eric B, Appleton Allison A, Kawachi Ichiro, Kubzansky Laura D, Non Amy L, Buka Stephen, Gilman Stephen E

机构信息

Department of Epidemiology and Biostatistics, University of Maryland College Park, School of Public Health, College Park, United States.

Department of Epidemiology, Brown University, Providence, United States.

出版信息

Psychoneuroendocrinology. 2015 Jan;51:403-13. doi: 10.1016/j.psyneuen.2014.10.016. Epub 2014 Oct 25.

Abstract

BACKGROUND

Children exposed to social adversity carry a greater risk of poor physical and mental health into adulthood. This increased risk is thought to be due, in part, to inflammatory processes associated with early adversity that contribute to the etiology of many adult illnesses. The current study asks whether aspects of the prenatal social environment are associated with levels of inflammation in adulthood, and whether prenatal and childhood adversity both contribute to adult inflammation.

METHODS

We examined associations of prenatal and childhood adversity assessed through direct interviews of participants in the Collaborative Perinatal Project between 1959 and 1974 with blood levels of C-reactive protein in 355 offspring interviewed in adulthood (mean age=42.2 years). Linear and quantile regression models were used to estimate the effects of prenatal adversity and childhood adversity on adult inflammation, adjusting for age, sex, and race and other potential confounders.

RESULTS

In separate linear regression models, high levels of prenatal and childhood adversity were associated with higher CRP in adulthood. When prenatal and childhood adversity were analyzed together, our results support the presence of an effect of prenatal adversity on (log) CRP level in adulthood (β=0.73, 95% CI: 0.26, 1.20) that is independent of childhood adversity and potential confounding factors including maternal health conditions reported during pregnancy. Supplemental analyses revealed similar findings using quantile regression models and logistic regression models that used a clinically-relevant CRP threshold (>3mg/L). In a fully-adjusted model that included childhood adversity, high prenatal adversity was associated with a 3-fold elevated odds (95% CI: 1.15, 8.02) of having a CRP level in adulthood that indicates high risk of cardiovascular disease.

CONCLUSIONS

Social adversity during the prenatal period is a risk factor for elevated inflammation in adulthood independent of adversities during childhood. This evidence is consistent with studies demonstrating that adverse exposures in the maternal environment during gestation have lasting effects on development of the immune system. If these results reflect causal associations, they suggest that interventions to improve the social and environmental conditions of pregnancy would promote health over the life course. It remains necessary to identify the mechanisms that link maternal conditions during pregnancy to the development of fetal immune and other systems involved in adaptation to environmental stressors.

摘要

背景

暴露于社会逆境中的儿童成年后身心健康状况不佳的风险更高。这种风险增加被认为部分归因于与早期逆境相关的炎症过程,这些炎症过程促成了许多成人疾病的病因。当前的研究探讨产前社会环境的各个方面是否与成年期的炎症水平相关,以及产前和童年时期的逆境是否都对成人炎症有影响。

方法

我们通过对1959年至1974年间参与围产期协作项目的参与者进行直接访谈,评估产前和童年时期的逆境情况,并对355名成年后接受访谈的后代(平均年龄 = 42.2岁)的血液中C反应蛋白水平进行了检测。使用线性和分位数回归模型来估计产前逆境和童年逆境对成人炎症的影响,并对年龄、性别、种族和其他潜在混杂因素进行了调整。

结果

在单独的线性回归模型中,高水平的产前和童年逆境与成年期较高的C反应蛋白水平相关。当同时分析产前和童年逆境时,我们的结果支持产前逆境对成年期(对数)C反应蛋白水平有影响(β = 0.73,95%置信区间:0.26,1.20),这一影响独立于童年逆境以及包括孕期报告的母亲健康状况在内的潜在混杂因素。补充分析使用分位数回归模型和使用临床相关C反应蛋白阈值(>3mg/L)的逻辑回归模型得出了类似的结果。在一个纳入童年逆境的完全调整模型中,高产前逆境与成年期C反应蛋白水平升高3倍的几率相关(95%置信区间:1.15,8.02),这表明存在心血管疾病的高风险。

结论

产前时期的社会逆境是成年期炎症升高的一个风险因素,独立于童年时期的逆境。这一证据与表明孕期母亲环境中的不良暴露对免疫系统发育有持久影响的研究一致。如果这些结果反映了因果关联,那么它们表明改善孕期社会和环境条件的干预措施将促进一生的健康。确定孕期母亲状况与胎儿免疫及其他参与适应环境应激源的系统发育之间联系的机制仍然很有必要。

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