Early Life Nutrition and Lifelong Health - Derbyshire Local Medical ...

BMA Board of ScienceAssociations between maternal obesity, diabetes, raised birth weight andadulthood diseaseThe rising birth weight in developed countries (with the possible exception of Japan) 98 associated withthe increasing incidence of obesity in pregnancy and related gestational diabetes, also has potential fordetrimental influences on the developing child. 99, 100 There is a U shaped relationship between birth weightand later insulin resistance and obesity, 59, 101 and there is now good evidence that children of women whoare diabetic in pregnancy are themselves more likely to develop insulin resistance in later life and tobecome overweight. 96 Initially shown in the Pima Indians, a population with a very high incidence ofdiabetes, this seems to occur in all populations. School children in Taiwan showed a similar phenomenon 102and Indian children of gestationally diabetic mothers had increased adiposity and hyperinsulinaemia. 103While this may represent in part a genetically inherited disorder, studies of sibling pairs discordant formaternal diabetes show that the effect occurs only in the offspring prenatally exposed to diabetes, stronglysuggesting a diabetic trait acquired during development. 104, 105 Infants of mothers with gestational diabeteshave a greater neonatal fat mass independent of birth weight 106 and it is reported that a high rate ofchildhood metabolic syndrome (central adiposity, insulin resistance and hypertension) occurs in large-forgestational-age(LGA) babies born to mothers with gestational diabetes 26 compared with appropriate-forgestational-age(AGA) babies. Importantly, the risk of metabolic syndrome is also present, but to a lesserextent, in LGA babies from normoglycaemic mothers. In a recent trial of two diets, normoglycaemicmothers on a high glycaemic index diet gave birth to more LGA babies. 107 Children of mothers with higherglucose concentrations within the normal range are more adipose. 27 Higher birth weight innormoglycaemic pregnancies is generally associated with raised adulthood BMI, and larger babies tend tobecome heavier adults. Although detailed investigations of the relative contributions of lean and fat mass108, 109have sometimes suggested that this association reflects increased lean body mass rather that fat mass,a recent study of infants from obese normoglycaemic mothers shows clear evidence of increasedadiposity. 110 To date there have been few attempts to define accurately the relationship between maternal,childhood and adulthood body composition over any range of maternal BMI. Ongoing prospectivelongitudinal studies in contemporary cohorts such as the Avon Longitudinal Study of Parents and Children(ALSPAC) cohort in Avon UK 111 and the Southampton Women’s Survey (SWS) 112 will be very informative inthis regard. In the latter it is already clear that mother’s body composition and dietary balance beforepregnancy can affect fetal cardiovascular development in late gestation. 113Key messageExtremes of maternal body composition, either excessive thinness or obesity, are associated withadverse patterns of fetal and infant development leading to poorer long-term health.Transgenerational effectsThere is concern that the detrimental effects of the nutritional transition in many populationsaround the world will have an effect on the risk of chronic disease which will persist for severalgenerations. Animal studies show that a dietary or glucocorticoid challenge administered inpregnancy can have effects on the metabolism, cardiovascular function and gene expression in thegrand-offspring, even without any additional challenge in the second generation. 74, 114 The effectscan involve epigenetic changes. 73 Similar changes have been reported in humans exposed to poornutrition during childhood development 115 including the intriguing possibility that the effects canbe transmitted through the paternal as well as the maternal line. There is now much interest in theconcept that non-genomic inheritance can affect more than one successive generation, both fromscientific, social and medical perspectives. 7522Early life nutrition and lifelong health