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

Abstract

Purpose of review: The concept of the developmental origins of health and disease susceptibility is rapidly attracting interest and gaining prominence as a complementary approach to understanding the causation of many complex common disorders that confer a major burden of disease; however several important issues and questions remain to be addressed, particularly in the context of humans.

Recent findings: In this review we enunciate some of these questions and issues, review empirical evidence primarily from our own recent studies on prenatal stress and stress biology, and discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate mechanisms that may underlie and mediate short-term and long-term effects of prenatal stress on the developing human embryo and fetus, with a specific focus on body composition, metabolic function, and obesity risk.

Summary: The implications for research and clinical practice are discussed with a summary of recent advances in noninvasive methods to characterize fetal, newborn, infant, and child developmental and health-related processes that, when coupled with available state-of-the-art statistical modeling approaches for longitudinal, repeated measures time series analysis, now afford unprecedented opportunities to explore and uncover the developmental origins of human health and disease.

Figure 1. Conceptual framework of a biobehavioral model in humans of prenatal stress-related maternal–placental–fetal endocrine and immune processes and programming of health and disease risk

Figure 2. Mean glucose, insulin, C-peptide, and leptin responses (±SEM) to an oral glucose tolerance test in prenatally stressed (PS, ‘black circles’) and comparison group (CG, ‘white triangles’) individuals (left panel)

Glucose levels were not significantly different across the groups, however, PS individuals showed significantly elevated 2 h insulin (P=0.01) and C-peptide levels (P=0.03), as well as higher leptin levels at all time points during the oral glucose tolerance test (OGTT) (P=0.05). In addition, PS individuals had a higher % body fat and a higher BMI (P=0.04, right panel). Adapted with permission from [23].