Fetal origins of obesity, cardiovascular disease, and type 2 diabetes

Abstract

The first 1,000 days of life is a critical window of development, determining susceptibility to adult obesity and cardiometabolic health [1,2]. Environmental insults during this rapid development phase may result in irreversible adverse outcomes. Animal and human studies provide evidence for the fetal origins of adult noncommunicable disease hypothesis [3–5]. This hypothesis suggests that intrauterine exposures affect the fetus’s development during sensitive periods, and increases the risk of noncommunicable diseases in adult life [3–5]. Systematic reviews confirm evidence of inverse epidemiological associations between birth weight and later development of hypertension [2] and coronary heart disease [6]. The fetal origins of disease hypothesis has been challenged as a possible statistical artifact [7], but has been confirmed by later studies with high follow-up rates and adjustment for confounders [8,9]. Early animal studies of severe undernutrition [10] and later human studies both showed a relation between fetal stressors and subsequent development of chronic diseases [3,4]. Natural experiments such as the Dutch famine cohort showed that prenatal undernutrition was associated with low birth weight, followed by adult obesity and glucose intolerance when adults were raised outside of a famine environment [11]. Birth weights and cardiovascular death rates studied in men born during 1911 to 1930 in the United Kingdom showed that low birth weight was associated with hypertension and ischemic heart disease mortality [3]. In adults born in Finland between 1924 and 1933, and who were followed up in 1971, the incidence of type 2 diabetes increased with decreasing birth size and placental weight [12]. Based on these early studies, small birth size was regarded as a marker of poor fetal nutrition and intrauterine growth restriction, independent of gestational age. Fetal programming and low fetal growth rates increased susceptibility to adult diseases [4], and promoters of preand postnatal growth were regarded as protective against ischemic heart disease [3]