The influence of vitamin supplementation on longitudinal patterns of maternal vitamin status from preconception to post-delivery

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Dec 11 2023

In a recent study published in PLoS Medicine, researchers secondary analyzed the NiPPeR randomized clinical trial (RCT) data to assess maternal vitamin levels pre-conception, during pregnancy, and post-delivery and also explored the impact of vitamin supplementation before and during gestation.

Maternal vitamin levels are critical for a healthy pregnancy and child development. However, longitudinal information on vitamin level changes is sparse, and very few studies have examined the impact of pre-conception and prenatal vitamin supplementation. Multiple micronutrient supplementation is effective in low-middle-income nations; however, large-scale studies in high-income settings are limited, lowering agreement on individual or concomitant supplements.

About the study

In the present study, researchers examined maternal vitamin levels before, during, and six months post-pregnancy and determined the impact of vitamin supplements received before and during gestation.

In the double-blinded NiPPeR RCT, 1,729 females (across New Zealand, Singapore, and the United Kingdom) aged between 18 and 38 years who were planning pregnancy were randomly assigned to receive regular vitamin supplementation (control group, 859 individuals) or increased vitamin supplements (intervention group, 870 individuals) beginning in pre-conception and continuing throughout gestation, with staff and participants blinded. Both groups were supplemented with β-carotene, folic acid, calcium, iodine, and iron; additionally, the treatment group received vitamins B6, vitamin B12, vitamin D, riboflavin, [over-the-counter (OTC) supplementation quantities], myoinositol, zinc, and probiotics.

At gestation week 28, glucose tolerance, as determined using oral glucose tolerance tests, was the primary objective. The decrease in maternal insufficiencies of vitamin B6, riboflavin, vitamin D, and vitamin B12 prior to and throughout pregnancy was the secondary result reported in this study.

Maternal serum levels of vitamin D, vitamin B, and deficiency or insufficiency markers (methylmalonic acid, hydroxykynurenine ratio, homocysteine) were measured at recruitment, one month after starting intervention pre-conception, in the first trimester (weeks 7.0-11 of gestation), late-pregnancy period (around week 28 of gestation), and post-delivery (after six months of discontinuing supplements).

The researchers calculated standard deviation scores (SDS) representing longitudinal alterations among control group participants and evaluated differences across study groups. Pregnant and nursing women, those with assisted conception, major food allergies, pre-existing diabetes mellitus, hormonal contraceptive usage, systemic steroids, metformin, anti-convulsants, or drugs for hepatitis B or C, and human immunodeficiency virus (HIV) infections were excluded from the NiPPeR trial.

Maternal blood samples were obtained from both groups before conception, during ethe initial and late pregnancy periods, and six months after birth among women who got pregnant. In total, 580 women had singleton pregnancies that met the research requirements and reached 28 weeks gestation, with 512 being followed up six months after birth. Interviewer-administered questionnaires were used to gather sociodemographic information, menstrual, obstetric, health histories, and lifestyle behaviors. Liquid chromatography-tandem mass spectrometry was used to determine vitamin levels in serum.

Results

At enrollment, the percentage of participants with marginal and low serum levels was 29% for folate (less than 14 nmol per L), 8.0% and 82% for riboflavin (less than 5.0 nmol per L and 27 nmol per L, respectively), nine percent for B12 vitamin (less than 221 pmol per L), and 49% for 25-hydroxyvitamin D (less than 50 nmol per L); the percentages were balanced across study groups. At enrollment, more than 90% of participants had poor or marginal levels for at least one vitamin. Serum riboflavin levels in controls decreased during the initial and late pregnancy periods although vitamin D levels remained unaltered in the first trimester, and B6 vitamin and B12 vitamin levels decreased throughout pregnancy, reaching >1.0 standard deviation score lower compared to baseline by gestation week 28.

Among controls, 54% had poor vitamin B6 levels (pyridoxal 5-phosphate less than 20.0 nmol/L) at gestation week 28. Serum levels of supplement constituents were significantly higher in the interventional group than in controls after a month of supplementing with riboflavin, B6 vitamin, B12 vitamin B12, and D vitamin by 0.8 SDS, 1.1 SDS, 0.6 SDS, and 0.5 SDS, respectively, with persistently elevated levels in serum among intervention group participants during pregnancy.

Vitamin deficiency and insufficiency indicators were lower among intervention group participants, and the percentage of vitamin D-insufficient individuals (below 50.0 nmol/L) at gestation week 28 was lower among intervention group participants (35% vs. 8.5%). Even six months after birth, the interventional group's serum vitamin B12 levels remained higher than the controls (by 0.3 SDS). Sensitivity analysis demonstrated that the group differences were robust to location, ethnicity, and parity adjustments.

Conclusion

Overall, the study findings showed that more than 90% of research participants had low levels of at least one vitamin throughout pre-conception and pregnancy, with many women having vitamin B6 insufficiency late in pregnancy. The deficits were dramatically alleviated by over-the-counter (OTC) pre-conception and pregnancy supplements. The study indicates that women in higher-income nations should reconsider their dietary guidelines and explore several micronutrient supplementations. However, high-resource situations and a lack of Amerindians and Africans limit the generalizability of the findings.