Effect of supplemental nutrition in pregnancy on offspring’s risk of cardiovascular disease in young adulthood: long-term follow-up of a cluster trial from India

Background
Undernutrition during intrauterine life and early childhood is hypothesised to increase the risk of cardiovascular disease (Developmental Origins of Health and Disease Hypothesis), but experimental evidence from humans is limited. This hypothesis has major implications for control of the cardiovascular disease epidemic in South Asia (home to a quarter of world’s population), where a quarter of newborns have low birth weight. We investigated whether in an area with prevalent undernutrition supplemental nutrition offered to pregnant women and her offspring below the age of 6 years was associated with a lower risk of cardiovascular disease in the offspring when they were young adults.

Methods and findings
The Hyderabad Nutrition Trial was a community-based non-randomised controlled intervention trial conducted in 29 villages near Hyderabad, India (1987-90). Protein-calorie food supplement was offered daily to pregnant and lactating women (2.09MJ energy and 20-25g protein) and their offspring (1.25MJ energy and 8-10g protein) until the age of six years in the 15 intervention villages, but not in the 14 control villages. A total of 1826 participants (949 from the intervention villages and 877 from the control villages, representing 70% of the cohort) at a mean age of 21.6 years (62% males) were examined between 2009 and 2012. The mean body mass index of the participants was 20kg/m2 and the mean systolic blood pressure was 115mm Hg. The age, sex, socio-economic position and urbanisation-adjusted effects of intervention (beta-coefficients and 95% confidence intervals) on outcomes were: carotid intima-media thickness, 0.01mm (-0.01 to 0.03), p=0.36; arterial stiffness (augmentation index), -1.1% (-2.5 to 0.3), p=0.097; systolic blood pressure, 0.5mm Hg (-0.6 to 1.6), p=0.36; body mass index, -0.13kg/m2 (-0.75 to 0.09), p=0.093; low-density lipoprotein cholesterol, 0.06 mmol/l (-0.07 to 0.2), p=0.37; and fasting insulin (log), -0.06mU/l (-0.19 to 0.07), p=0.43. The limitations of this study include non-randomised allocation of intervention and lack of data on compliance, and potential for selection bias due to incomplete follow-up.

Conclusions
Our results showed that in an area with prevalent undernutrition protein-calorie food supplements offered to pregnant women and their offspring below the age of 6 years were not associated with lower levels of cardiovascular risk factors among offspring when they were young adults. Our findings, coupled with evidence from other intervention studies to date, suggest that policy makers should attach limited value to cardiovascular health benefits of maternal and child protein-calorie food supplementation programs.