Vitamin A Supplementation during Pregnancy Enhances Pandemic H1N1 Vaccine Response in Mothers, but Enhancement of Transplacental Antibody Transfer May Depend on When Mothers Are Vaccinated during Pregnancy.

Background: In the growing embryo, the vitamin A requirement is tightly regulated. Maternal vitamin A deficiency during pregnancy may alter maternal immune function to accommodate the fetus.

Objective: Our primary objective was to determine the effect of oral vitamin A supplementation (VAS) during pregnancy and until 6 mo postpartum on pandemic H1N1-vaccine responses in mothers and their infants at 6 mo of age.

Methods: In this randomized controlled clinical trial, pregnant women (n = 112) during the second trimester (mean ± SD: 14 ± 1 wk) were assigned to receive either an oral dose of 10,000 IU vitamin A or placebo weekly until 6 mo postpartum. During the third trimester, mothers received a single dose of inactivated pandemic H1N1-influenza vaccine. Hemagglutination-inhibition (HAI) titer was measured in cord, infant, and maternal blood samples. Multivariate regressions with adjustments were used for data analysis.

Results: Seventy-six percent of women had low plasma retinol concentrations (<1.05 μmol/L) in their second trimester. VAS of mothers increased vitamin A concentrations in cord blood by 21.4% and in colostrum by 40.7%. At 6 mo postpartum, women in the vitamin A group had 38.7% higher HAI titers and a higher proportion of HAI titer of ≥1:40 of the cutoff compared with the placebo group. A total of 54.5% of infants had an HAI titer ≥1:40 at 6 mo of age, but there was no difference in HAI titer in infants between groups. Overall, HAI in cord blood did not differ between groups, but in the placebo group, cord blood HAI was negatively associated with maternal "vaccination-to-delivery intervals" (rs = -0.401; P = 0.5), and maternal VAS increased cord blood HAI 6-fold if antenatal immunization was administered ≥10 wk before delivery.

Conclusions: In a community with low vitamin A status, weekly maternal VAS during pregnancy and postpartum increases the breast-milk vitamin A concentration and enhances prenatal H1N1-vaccine responses in mothers, but the benefits of maternal VAS in transplacental antibody transfer may depend on the time of gestation when mothers were vaccinated. This trial was registered at clinicaltrials.gov as NCT00817661.