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

BMA Board of Sciencediseases including cardiovascular and metabolic disease, ‘precocious’ puberty, osteoporosisand some forms of cancer. Understanding the epigenetic processes thus holds the key tounderstanding the underlying pathophysiology and to developing approaches to early diagnosis,prevention and treatment of these diseases (see Appendix 1).Maternal undernutrition and long-term outcomes in the offspringNewborn size is related to maternal energy balance, increasing with the mother’s BMI andadiposity. Her height, and independently leg length, head circumference and birth weight, predictthe baby’s size, suggesting that her own early nutritional biology influences how she nourishes thefetus. 86, 87 The ‘fetal origins hypothesis’ proposed that maternal ill health, poverty and undernutritionimpair fetal and infant growth and were root causes of adult chronic disease. 88 If this is so, indicesof poor maternal nutrition would be associated with cardiovascular disease or its risk factors in theoffspring. So far, unfortunately, there are only crude data available to test this.There is very little evidence concerning the effects of maternal undernutrition and nutrition in thedeveloping world on the longer term health of the offspring. Studies in developing or historicallypoor countries have shown that low maternal weight, BMI or skinfold thickness in pregnancy areassociated with higher offspring blood pressure, 89, 90 insulin resistance 91, 92 and risk of CHD. 93 Followupof people exposed to the 1944-45 Dutch Hunger Winter showed that exposure of the motherto acute famine was associated with increased cardiovascular risk in the adult offspring. Outcomesvaried according to the timing of famine exposure; 94 late gestation exposure was associated withgreater risk of glucose intolerance and early gestation exposure with obesity, atherogenic lipidprofiles and CHD. Famine effects were independent of birth weight, suggesting that maternalundernutrition may impair adult health without reducing size at birth.The Institute of Nutrition of Central America and Panama (INCAP) trial in Guatemala (1969-77) isthe only randomised trial of a nutritional intervention in which cardiovascular risk factors have beenmeasured in the adult offspring. 95 In the original trial, pregnant women and children received one oftwo supplements: a high-protein, high-energy drink or a lower nutrient drink. There was nodifference in birth weight between these two groups but the children of mothers who received ahigh-protein, high-energy drink had lower blood triglyceride and higher high-density lipid (HDL)cholesterol concentrations in adult life (profiles usually associated with better cardiovascular health).The Pune Maternal Nutrition Study was set up specifically to investigate the relationship ofmaternal nutrition to the children’s future risk of diabetes and heart disease. It collectedprospective information on diet, workload and micronutrient status in pregnant women in ruralIndian villages. At six years of age the children were thin by international standards but had ahigher percentage body fat than European children. Maternal folate concentrations predictedhigher insulin resistance in the child, and children born to mothers with the lowest vitamin B12concentrations and highest folate concentrations were the most insulin resistant. 96, 97 Thus animbalance in the mother in two vitamins important in methyl group provision predicted higheradiposity and insulin resistance in the child, suggesting an important role for 1-carbon metabolismin the developmental origins of type 2 diabetes.Early life nutrition and lifelong health 21