In a recent study published in The Lancet, researchers evaluated the effects of maternal vitamin B12 (cyanocobalamin) supplementation on the neurodevelopment and growth of infants born in Nepal.

Study: The effect of vitamin B12 supplementation during pregnancy on infant growth and development in Nepal: a community-based, double-blind, randomised, placebo-controlled trial. Image Credit: NatchaS/Shutterstock.com

Background

Children born in low- and middle-income nations may not attain full growth and neurodevelopment due to the prevalence of low or marginal cyanocobalamin levels in the blood.

Cyanocobalamin is critical for various physiological processes in the human body, especially neurological functions.

Cyanocobalamin is especially essential during gestation and early infancy to improve pregnancy outcomes and enhance the growth and neurodevelopment of infants.

Assessing neurological outcomes among infants following cyanocobalamin administration to mothers during pregnancy could inform decision- and policy-making concerning antenatal care.

About the study

In the present study, researchers investigated whether administering vitamin B12 supplements to mothers from the initial gestational period till six months post-delivery could improve neurodevelopment outcomes in neonates born in Nepal.

The double-blinded, community-based, placebo-controlled clinical trial included 800 expecting women, 20.0 to 40.0 years of age, who had completed a maximum of 15.0 weeks of gestation.

The participants were randomly assigned in a 1:1 ratio (1:1) to receive 50.0 μg of oral cyanocobalamin daily (intervention group, n=400) or a placebo (placebo group, n=400) until six months post-delivery.

The participants were recruited from home visits and outpatient health departments of three Nepali hospitals between March 28, 2017, and October 15, 2020. Scientists generated the allocation list independently, linking the participants’ personal identification numbers.

The participants and investigators were blinded to the intervention, and the participants were followed up through May 18, 2022. Serum samples were obtained from the participants to measure vitamin B12 levels, expressed as pmol/L.

The primary study outcomes were the linear growth, evaluated using the length-for-age Z scores (LAZ) at one year of age 12, and neurodevelopment, evaluated using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III) cognitive composite scores of six months and one year of age.

Secondary outcomes included stillbirths, infant deaths, and adverse events (AEs). The team assessed the study outcomes among the intention-to-treat (ITT) sampled population.

Stillbirths, miscarriages, infant births lost to follow-up, and those born to mothers who chose to discontinue were excluded from the analysis. In addition, individuals were excluded from outcome analysis at six months of age due to infant birth outside of the window period or if their mothers were unwilling to travel due to the COVID-19 pandemic.

Results

At study initiation, 569 women (71.0%) had serological vitamin B12 levels of less than 221.0 pmol/L, indicative of marginal or low vitamin B12 status.

In the intervention group, out of 400 women, 23 were lost to follow-up, three women refused to continue, 19 women had miscarriages or medical termination of pregnancy, and 377 live births were reported.

In the placebo group of 400 women, 17 women were lost to follow-up, one woman refused to continue, eight women had miscarriages or their pregnancy was medically terminated, and 383 live births were reported.

In both groups, 47 participants (6.0%) were lost to follow-up, largely due to spontaneous abortions or medical termination of pregnancy. Infant deaths or stillbirths were observed for three (1.0%) and nine (2.0%) women in the intervention and placebo groups, respectively.

Vitamin B12 supplementation did not significantly affect the primary study outcomes, despite considerable improvements in serological vitamin B12 levels among mothers.

The mean length-for-age Z scores obtained at one year of age were -0.570 and -0.550 for the intervention (366 neonates) and placebo groups (363 neonates), respectively, with a 0.020 difference in the mean.

The mean Bayley-III scores were slightly greater among vitamin B12-treated participants (97.70, 364 infants) than among placebo-treated participants (97.10, 361 infants), with a 0.50 difference in the mean.

Conclusions

Overall, the study findings showed that despite vitamin B12 being deficient among Nepali pregnant women and the considerable improvement in serological vitamin B12 levels following vitamin B12 administration to mothers between early pregnancy and six months post-delivery, the supplementation of vitamin B12 (50.0 μg vitamin B12 daily) did not significantly improve neonatal growth and development.

The study findings underpin the existing antenatal pregnancy guidelines published by the World Health Organization (WHO) of no regular supplementation of vitamin B12 to mothers during the gestational period.