Abstract
BackgroundThe Pune Maternal Nutrition Study (PMNS) was established to prospectively study the relationship of maternal nutrition to fetal growth and later cardiometabolic risk in the offspring. High homocysteine and low vitamin B12 levels in pregnancy predicted lower birthweight and higher insulin resistance at 6 years in the offspring. B12 deficiency was widespread in this population, due to low dietary intake. We therefore commenced a community-based intervention study with the underlying hypothesis that vitamin B12 supplementation of adolescent members of the PMNS cohort will improve birth weight, B12 status, and reduce future diabetes risk, in their offspring.MethodsThe individually randomised controlled trial commenced in September 2012, with boys and girls randomized into 3 groups, to receive daily for at least 3 years or until the birth of their first child: 1) vitamin B12 2 μg; or 2) vitamin B12 2 μg plus multiple micronutrients (MMN) plus 20 g of milk powder or 3) placebo. Iron and folic acid is given to all participants. Compliance is assessed by monthly supplement counts. Adverse events are recorded using a standardised questionnaire. The primary outcome is cord blood B12 concentration; based on 180–200 pregnancies in the girls, the study has ~80% power to detect a 0.5 SD change in newborn B12, in the B12 supplementation groups compared with controls, at the 5% significance level. Primary analysis will be by intention to treat.DiscussionOur study tests a primordial prevention strategy through an intergenerational intervention started pre-conceptionally in both boys and girls using physiological doses of micronutrients to improve immediate pregnancy-related and long-term cardio metabolic outcomes. The results will have significant public health implications in a setting with widespread B12 deficiency but relative folate sufficiency. The randomised controlled trial design allows us to be confident that our findings will be causally relevant.Trial registrationISRCTN 32921044, applied on 14/09/2012. CTRI 2012/12/003212, registered on 02/12/2012. Retrospectively registered.
Highlights
The Pune Maternal Nutrition Study (PMNS) was established to prospectively study the relationship of maternal nutrition to fetal growth and later cardiometabolic risk in the offspring
Current preventive strategies to reduce the burden of type 2 diabetes mellitus (T2DM) focus mainly on improving the lifestyle of middle-aged individuals with pre-existing disease or risk factors
David Barker’s ‘fetal programming’ hypothesis [1] suggests that alterations in the nutritional supply during critical stages of intrauterine growth permanently alter the structure and function of the fetal organs and offers a novel primary prevention strategy. This idea was based on findings, initially in the UK, that the prevalence of coronary heart disease, T2DM and impaired glucose tolerance was higher in adults who had lower birth weights [2]
Summary
The Pune Maternal Nutrition Study (PMNS) was established to prospectively study the relationship of maternal nutrition to fetal growth and later cardiometabolic risk in the offspring. David Barker’s ‘fetal programming’ hypothesis [1] suggests that alterations in the nutritional supply during critical stages of intrauterine growth permanently alter the structure and function of the fetal organs and offers a novel primary prevention strategy This idea was based on findings, initially in the UK, that the prevalence of coronary heart disease, T2DM and impaired glucose tolerance was higher in adults who had lower birth weights [2]. These findings were replicated in different parts of the world, Kumaran et al BMC Nutrition (2017) 3:41 including India [3,4,5,6,7]. The fetal programming hypothesis was expanded to include postnatal factors and evolved into the ‘developmental origins of health and disease’ hypothesis (DOHaD)
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