Interactions of perturbations in intrauterine growth and growth during childhood on the risk of adult-onset disease.

The 'fetal origins' hypothesis (Barker, 1995) would predict that the rising epidemic of diabetes and CHD in India would be due to poor intrauterine growth of the Indian babies. While this explanation may be valid to an extent, the higher prevalence of these disorders in urban compared with rural India (where birth weights are lower) would suggest a significant role for postnatal factors. In a cohort of 477 children born in the King Edward Memorial Hospital, Pune, we found that at 8 years of age current obesity strongly predicted insulin resistance. When this effect was allowed for, low birth weight was significantly associated with insulin-resistance variables and other cardiovascular risk factors. Children who were born small but had grown heavy (or tall) were the most insulin resistant and had the highest levels of cardiovascular risk factors. Accelerated growth in relation to mid parental height was similarly predictive. Poor intrauterine growth also predicted higher central adiposity at 8 years of age. We have also studied maternal nutrition and fetal growth in six villages near Pune. A newborn Indian baby is small (2650 g, SD score (SDS) -1.6 compared with an average white Caucasian baby born in the UK) and 'thin' (ponderal index 2.45 kg/m3, SDS -1.2), but has preserved its subcutaneous fat (subscapular skinfold thickness SDS -0.6). The thinness of the Indian babies is due to poor muscle and small abdominal viscera. We have proposed this composition as the 'thrifty phenotype' (Hales & Barker, 1992) of Indian babies. Maternal size and intake of certain food groups during pregnancy were important determinants of the baby's phenotype. Thus, the small Indian babies are programmed to deposit fat from their intrauterine life. Exaggeration of this tendency in later life is associated with insulin-resistance syndrome. Control of the insulin-resistance epidemic in India might depend on improved intrauterine development and prevention of childhood obesity.