
Optimal maternal nutritional status before and during pregnancy is vital for healthy pregnancy and development of a healthy baby. Long-term data on the nutritional status during various stages of pregnancy and postpartum is lacking. In addition, the impact of micronutrient supplementation on vitamin status during pregnancy remains uncertain.
A recent study by Godfrey et al., published in the journal, PLOS Medicine reported low levels of certain vitamins (folate, riboflavin, vitamin B12, and vitamin D) among women in the preconception stage. The study further confirmed that micronutrient supplementation, before and during pregnancy in amounts available in over-the-counter supplements can reduce vitamin deficiency during pregnancy. Supplementation of vitamin B12 before and during pregnancy was associated with higher B12 levels in maternal plasma even during the lactation period.
The NiPPeR (Nutritional intervention preconception and during pregnancy to maintain healthy glucose metabolism and offspring health) trial is a multicentre, double-blind, randomized controlled study, which included 1,729 women (age: 18–38 years), who were planning to conceive. The primary aim was to assess glucose tolerance at 28 weeks’ gestation. The secondary aim was to evaluate the pattern of changing micronutrient status before pregnancy and throughout pregnancy, and to evaluate the impact of micronutrient supplementation on the level of vitamins, before and during pregnancy.
Participants were randomly divided into 2 groups: control group (n = 859) and the intervention group (n = 870). Both the groups received folic acid, beta-carotene, iron, calcium, and iodine, and the intervention group additionally received riboflavin, vitamin B6, vitamin B12, and vitamin D, along with myo-inositol, probiotics, and zinc. Maternal plasma concentrations of vitamins and their deficiency markers were assessed at the time of recruitment, 1 month after starting preconception intervention, during early pregnancy (7 to 11 weeks’ gestation), late pregnancy (around 28 weeks’ gestation), and post-delivery (6 months after supplement discontinuation). Standard deviation scores (SDS) representing longitudinal changes in the nutritional status was used to evaluate differences across the study groups.
The results are summarized below:
Prevalence of micronutrient deficiency: Over 90% of the enrolled participants in both the groups showed varying degree of micronutrient insufficiency/deficiency before pregnancy (Graphic A).
Higher proportion of participants in the control group reported deficiency in riboflavin, vitamin D, vitamin B6, and vitamin B12 at 28 weeks of gestation compared to the intervention group (Graphic B).
Effect of micronutrient supplementation
1. Folic acid supplementation: Both, the control and intervention group showed similar longitudinal pattern of change in folate levels over time (initial increase followed by post pregnancy decrease); increase in plasma homocysteine, a marker of folic acid and vitamin B complex insufficiency was less pronounced in the intervention group compared to the control group (0.40 vs. 0.65 SDS).
2. Riboflavin, vitamin D, and vitamin B6 supplementation: Plasma levels of riboflavin, vitamin D, and vitamin B6 were substantially higher in the intervention group after 1 month of supplementation (riboflavin by 0.8 SDS, vitamin D by 0.5 SDS, and vitamin B6 by 1.07 SDS) and was maintained till late pregnancy compared to the control group (p <0.0001).
3. Vitamin B12 supplementation: Higher levels of B12 (by 0.6 SDS) was noted in women in the intervention group compared to the control group at all stages of pregnancy; the levels were sustained till 6 months post-delivery (p <0.0001).

Clinical implication
The study highlights the importance of assessing and addressing vitamin insufficiencies/deficiencies in preconception women. The study underscores the role of multivitamin supplements to support optimal maternal vitamin status and potentially improve pregnancy outcomes.
(Source: Godfrey KM, Titcombe P, El-Heis S, Albert BB, Tham EH, Barton SJ, Kenealy T, Chong MF, Nield H, Chong YS, Chan SY, Cutfield WS; NiPPeR Study Group. Maternal B-vitamin and vitamin D status before, during, and after pregnancy and the influence of supplementation preconception and during pregnancy: Prespecified secondary analysis of the NiPPeR double-blind randomized controlled trial. PLoS Med. 2023;20(12):e1004260. Doi:10.1371/journal.pmed.1004260)