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 their 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 nonrandomised controlled intervention trial conducted in 29 villages near Hyderabad, India (1987-1990). Protein-calorie food supplement was offered daily to pregnant and lactating women (2.09 MJ energy and 20-25 g protein) and their offspring (1.25 MJ energy and 8-10 g protein) until the age of six years in the 15 intervention villages, but not in the 14 control villages. A total of 1,826 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 (BMI) of the participants was 20 kg/m(2)and the mean systolic blood pressure was 115 mm Hg. The age, sex, socioeconomic position, and urbanisation-adjusted effects of intervention (beta coefficients and 95% confidence intervals) on outcomes were as follows: carotid intima-media thickness, 0.01 mm (-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, 0.5 mm Hg (-0.6 to 1.6),p= 0.36; BMI, -0.13 kg/m(2)(-0.75 to 0.09),p= 0.093; low-density lipoprotein (LDL) cholesterol, 0.06 mmol/L (-0.07 to 0.2),p= 0.37; and fasting insulin (log), -0.06 mU/L (-0.19 to 0.07),p= 0.43. The limitations of this study include nonrandomised 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 programmes. Author summaryWhy was the study done? Some researchers say that poor nutrition of the mother in pregnancy can increase the risk of heart disease in her children. If true, this theory could help to explain the high risk of heart disease among South Asians, in whom low birth weight is very common. Evidence for this theory from intervention studies (in which some people are exposed to treatment and others are not) is limited. What did the researchers do and find? The Hyderabad Nutrition Trial was conducted previously (1987-1990) in an area with high levels of undernutrition in Telangana state, India; extra food (500 calories and 20 g protein) was offered daily to all pregnant women and their children below the age of 6 years in 15 villages out of a total of 29 villages. The researchers examined 1,826 children born during this trial when their average age was 22 years. They found no difference in risk of heart disease between offspring born to women who were offered extra food in pregnancy and childhood and those who were not. What do these findings mean? Our results showed that extra food offered to undernourished pregnant women may not lower their offspring's risk of heart disease in young adulthood. Our findings suggest that, until further evidence is available, policy makers should attach limited value to heart health benefits of food supplementation programmes for pregnant women and young children.