The Pune Rural Intervention in Young Adolescents (PRIYA) study: design and methods of a randomised controlled trial
Kalyanaraman Kumaran1,2, Pallavi Yajnik1, Himangi Lubree1
11Diabetes Unit, KEM Hospital Research Centre, Rasta Peth, Pune 411011 India.
Insights
Vitamin B12 supplementation in adolescents can improve birth weight and B12 status in their offspring, potentially reducing future diabetes risk. This intergenerational approach addresses widespread B12 deficiency for better long-term health outcomes.
Area of Science:
- Maternal and child health
- Nutritional science
- Public health
Background:
- Pune Maternal Nutrition Study (PMNS) identified links between maternal nutrition and offspring cardiometabolic risk.
- Low vitamin B12 levels during pregnancy predicted lower birthweight and higher insulin resistance in children.
- Widespread dietary vitamin B12 deficiency was observed in the study population.
Purpose of the Study:
- To test if vitamin B12 supplementation in adolescents improves birth weight and B12 status in their offspring.
- To evaluate the potential of this intervention to reduce future diabetes risk in the next generation.
- To implement a primordial prevention strategy through an intergenerational micronutrient intervention.
Main Methods:
- Individually randomized controlled trial involving adolescent boys and girls.
- Supplementation groups received daily vitamin B12 (2 mcg), vitamin B12 plus multiple micronutrients (MMN), or placebo for at least 3 years.
- Primary outcome measured was cord blood B12 concentration; intention-to-treat analysis used.
Main Results:
- The study is powered to detect a 0.5 SD change in newborn B12 levels.
- Compliance assessed by monthly supplement counts; adverse events recorded.
- Primary analysis will be by intention to treat.
Conclusions:
- The study employs a primordial prevention strategy targeting intergenerational health outcomes.
- Results have significant public health implications for regions with widespread vitamin B12 deficiency.
- Randomized controlled trial design ensures causal relevance of findings.
Background:
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. 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.
Methods:
The 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 microg; or 2) vitamin B12 2 microg 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.
Discussion:
Our 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 Registration:
ISRCTN 32921044, applied on 14/09/2012. CTRI 2012/12/003212, registered on 02/12/2012. Retrospectively registered.
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