Programming of maternal and offspring disease: impact of growth restriction, fetal sex and transmission across generations

Jean N Cheong, Mary E Wlodek, Karen M Moritz, James S M Cuffe

Babies born small are at an increased risk of developing a myriad of adult diseases. While growth restriction increases disease risk in all individuals, often a second-hit is required to unmask "programmed" impairments in physiology. Programmed disease outcomes are demonstrated more commonly in male offspring compared to females, with these sex-specific outcomes partly attributed to different placental regulated growth strategies of the male and female fetus. Pregnancy is known to be a major risk factor for unmasking a number of conditions and can be considered a "second-hit" for women who were born small. As such female offspring often develop impairments of physiology for the first time during pregnancy, which present as pregnancy complications. Numerous maternal stressors can further increase the risk of developing a maternal complication during pregnancy. Importantly, these maternal complications can have long-term consequences for both the mother after pregnancy and the developing fetus. Conditions such as preeclampsia, gestational diabetes and hypertension, as well as thyroid, liver and kidney diseases are all conditions that can complicate pregnancy and have long-term consequences for maternal and offspring health. Babies born to mothers who develop these conditions are often at a greater risk of developing disease in adulthood. This has implications as a mechanism for transmission of disease across generations. In this review, we discuss the evidence surrounding long-term intergenerational implications of being born small and/or experiencing stress during pregnancy on programming outcomes. This article is protected by copyright. All rights reserved.