Elsevier

Psychoneuroendocrinology

Volume 51, January 2015, Pages 403-413
Psychoneuroendocrinology

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

https://doi.org/10.1016/j.psyneuen.2014.10.016Get rights and content

Highlights

  • Prenatal adversity is associated with adult CRP, independent of childhood adversity.

  • High prenatal adversity was associated with a 3-fold elevated odds of high-risk CRP.

  • It remains necessary to identify underlying mechanisms for the observed associations.

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 (>3 mg/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.

Section snippets

Sample

Participants were offspring of pregnant women enrolled between 1959 and 1966 in the Collaborative Perinatal Project (CPP) (Broman et al., 1975, Niswander and Gordon, 1972). At the time of enrollment, expectant mothers provided comprehensive data on health, behavior, and demographic characteristics; subsequent information on mothers and their offspring was collected at birth and periodically through the child's first 7 years. The New England Family Study (NEFS) was initiated to locate and

Social adversity

We created composite scores of social adversity prenatally and during early childhood (Evans et al., 2013, Sameroff, 1998). This approach accounts for the clustering of risk factors together, and allows for the examination of the inflammatory consequences of exposure to multiple forms of adversity at each time point. Consistent with prior research that has compared advantaged and disadvantaged groups of children into adulthood, we collapsed the prenatal and childhood adversity scores into

Analyses

Regression analyses were used to examine associations of prenatal and childhood adversity with CRP in adulthood. First, we conducted a series of linear regression models that evaluated associations between prenatal and childhood adversity and CRP, with scores for prenatal and childhood adversity included individually and together in the same model. If both prenatal and childhood adversity are associated with CRP independent of each other, coefficients for both prenatal and childhood adversity

Results

Characteristics of the sample are presented in Table 1. The sample had more females (57.75%) than males, and was predominantly white (80.66%). Ages at the adult follow-up ranged from 39 to 47 (mean ± SD, 42.07 ± 1.70). Approximately 37 percent of the sample was in the medium prenatal adversity category, and 8 percent of the sample was in the high prenatal adversity category. Considering childhood adversity, 44 percent of the sample was in the medium adversity category, and 9 percent was in the high

Discussion

We sought to investigate the independent associations of prenatal and childhood adversity with adulthood inflammation, consistent with a life course accumulation model. When prenatal and childhood adversity were considered separately, each was associated with higher levels of inflammation in adulthood after adjustment for individual characteristics (age, sex, race) and other potential confounders including pre-existing maternal health conditions. When we analyzed the effects of prenatal and

Role of the funding source

There has been no financial support for this work that could have influenced its outcome.

Conflict of interest statement

The authors have no conflicts of interest to report.

Acknowledgments

This research was supported by grants from the National Institutes of Health (MH087544, PI: Gilman; AG023397, PI: Buka), the Robert Wood Johnson Foundation (RWJF ID #67751), and the W. K. Kellogg Foundation (P3022586). We appreciate the contributions of Ms. Kathleen McGaffigan, our expert analyst and data manager.

References (56)

  • L.K. Rogers et al.

    Maternal inflammation, growth retardation, and preterm birth: Insights into adult cardiovascular disease

    Life Sci.

    (2011)
  • T. Roseboom et al.

    The Dutch famine and its long-term consequences for adult health

    Early Hum. Dev.

    (2006)
  • P. Sidebotham et al.

    Child maltreatment in the children of the nineties: deprivation, class, and social networks in a UK sample

    Child Abuse Negl.

    (2002)
  • N. Slopen et al.

    Internalizing and externalizing behaviors predict elevated inflammatory markers in childhood

    Psychoneuroendocrinology

    (2013)
  • S.E. Taylor et al.

    Relationship of early life stress and psychological functioning to adult C-reactive protein in the coronary artery risk development in young adults study

    Biol. Psychiatry

    (2006)
  • A.A. Appleton et al.

    Emotional functioning at age 7 years is associated with C-reactive protein in middle adulthood

    Psychosom. Med.

    (2011)
  • A.A. Appleton et al.

    The association between childhood emotional functioning and adulthood inflammation is modified by early-life socioeconomic status

    Health Psychol.

    (2012)
  • R.M. Baron et al.

    The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations

    J. Pers. Soc. Psychol.

    (1986)
  • Y. Ben-Shlomo et al.

    A life course approach to chronic disease epidemiology: conceptual models, empirical challenges and interdisciplinary perspectives

    Int. J. Epidemiol.

    (2002)
  • M.H. Bornstein

    Sensitive periods in development: structural characteristics and causal interpretations

    Psychol. Bull.

    (1989)
  • S.H. Broman et al.

    Preschool IQ: prenatal and early developmental correlates

    (1975)
  • A. Danese et al.

    Childhood maltreatment predicts adult inflammation in a life-course study

    Proc. Nat. Acad. Sci. U.S.A.

    (2007)
  • J. Danesh et al.

    C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease

    N. Engl. J. Med.

    (2004)
  • R. Dantzer et al.

    From inflammation to sickness and depression: when the immune system subjugates the brain

    Nat. Rev. Neurosci.

    (2008)
  • S. Entringer

    Impact of stress and stress physiology during pregnancy on child metabolic function and obesity risk

    Curr. Opin. Clin. Nutr. Metab. Care

    (2013)
  • S. Entringer et al.

    Prenatal stress and developmental programming of human health and disease risk: concepts and integration of empirical findings

    Curr. Opin. Endocrinol. Diabetes Obes.

    (2010)
  • S. Entringer et al.

    Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

    Proc. Nat. Acad. Sci.

    (2011)
  • S. Entringer et al.

    Influence of prenatal psychosocial stress on cytokine production in adult women

    Dev. Psychobiol.

    (2008)
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