Early life programming of health and disease: The long-term consequences of obesity in pregnancy

Abstract

The prevalence of overweight and obesity is rising in all parts of the world and, among young women, it presents a very clear danger during pregnancy. Women who are overweight or who gain excessive weight during pregnancy are at greater risk of complications in pregnancy and labour, and are more likely to lose their child to stillbirth or die themselves during pregnancy. This narrative review considers the evidence that, in addition to increasing risk of poor pregnancy outcomes, obesity has the capacity to programme foetuses to be at greater risk of cardiometabolic disorders later in life. An extensive body of evidence from prospective and retrospective cohorts, as well as record linkage studies, demonstrates associations of maternal obesity and/or gestational diabetes with cardiovascular disease, as well as type 1 and type 2 diabetes. Studies in animals suggest that these associations are underpinned by adaptations that occur in foetal life, which remodel the structures of major organs, including the brain, kidney and pancreas.

Keywords: cardiovascular disease; diabetes; disease; life phase; obesity; pregnancy; therapeutic areas.

Figure 1

The underlying determinants of health and disease are complex and vary across the lifespan. At all stages of life, health status is a product of gene–environment interactions. In early life, genetics plays a more important role than in later life. Risk of disease at all stages of life is a product of the outcomes of gene–environment interactions at earlier stages

Figure 2

The rising prevalence of obesity. (a) Overweight and obesity among adult women in selected countries. (b) Overweight and obesity among children aged 2–4 years in selected countries. Data from Ritchie and Roser. Aus, Australia; Can, Canada; Chn, China; Fra, France; Ger, Germany; Gre, Greece; UK, United Kingdom; USA, United States of America

Figure 3

Maternal and paternal factors modify genetically determined developmental potential to determine the foetal genotype at birth

Figure 4

Programming of disease in later life can be driven by both maternal under‐ and overnutrition

Figure 5

Remodelling of the structures of specific tissues in foetal life may explain how maternal obesity programmes offspring adiposity and metabolic function

Figure 6

The placenta must mediate the signal of maternal nutritional status to the foetus

Figure 7

A transgenerational cycle of obesity and related disorders