BALTIMORE – Three months of daily, oral treatment with a relatively high but safe dosage of a vitamin D supplement to pregnant mothers during late gestation followed by continued oral supplementation to their neonates during the first 6 months of life led to a significant reduction in the prevalence of dust-mite skin reactivity in those children once they reached 18 months old in a randomized, controlled trial with 259 mothers and infants.
And in a preliminary assessment that tallied the number of children who required primary care office visits for asthma through age 18 months, children who had received the highest vitamin D supplementation also showed a statistically significant reduction of these visits, compared with the placebo control children, Dr. Cameron C. Grant reported at the annual meeting of the Pediatric Academic Societies.
Dr. Cameron C. Grant
This suggestion that the vitamin D intervention could cut asthma development is not completely certain because in 18-month-old children, diagnosis of asthma is “very insecure,” noted Dr. Grant, a pediatrician at the University of Auckland, New Zealand and at Starship Children’s Hospital, also in Auckland. In addition, a limitation of the observed effect on dust mite atopy on skin-test challenge was that this follow-up occurred in only 186 (72%) of the 259 infants who participated in the study.
The study’s premise was that vitamin D is an immune system modulator, and that New Zealand provides an excellent setting to test the hypothesis that normalized vitamin D levels can help prevent development of atopy and asthma because many of the country’s residents are vitamin D deficient due to their diet and sun avoidance to prevent skin cancers. Results from prior studies had shown that 57% of New Zealand neonates have inadequate levels of vitamin D at birth, defined as a serum level of 25-hydroxyvitamin D of less than 20 ng/ml (less than 50 nmol/L), Dr. Grant noted.
“I think this intervention will only work in populations that are vitamin D deficient,” Dr. Grant said in an interview. In his study, the average serum level of 25-hydroxyvitamin D among control neonates was 38 nmol/L (about 15 ng/mL). In contrast, neonates born to mothers who had received a daily, higher-dose vitamin D supplement during the third trimester had serum measures that were roughly twice that level.
The study enrolled 260 pregnant women from the Auckland area with a single pregnancy at 26-30 weeks’ gestation; average gestational age at baseline was 27 weeks. Dr. Grant and his associates randomized the mothers to receive 1,000 IU oral vitamin D daily, 2,000 oral vitamin D daily, or placebo. The women delivered 259 infants. Infants born to women on the lower dosage supplement then received 400 IU vitamin daily for 6 months, those born to mothers on the higher level supplement received 800 IU vitamin D daily for 6 months, and those born to mothers in the placebo group received placebo supplements daily for 6 months.
Both supplement regimens led to statistically significant increases in serum levels of 25-hydroxyvitamin D in maternal serum at 36 weeks’ gestation, in cord blood at delivery, in the neonates’ serum at ages 2 months and 4 months, and in infant serum in the higher dosage group at 6 months of age, compared with similar measures taken at all these time points in the placebo group.
In addition, the neonates in the higher dosage group had significantly higher serum levels at 2, 4, and 6 months, compared with the lower dosage group. When measured a final time at 18-month follow-up, a year after the end of vitamin D supplementation, average serum levels of 25-hydroxyvitamin D in an three subgroups of children were virtually identical and similar to maternal serum levels at baseline. Dr. Grant and his associates had previously reported these findings and also had documented the safety of both the low and high levels of vitamin D supplements for both mothers and their children (Pediatrics. 2014 Jan;133[1]:e143-53).
The new findings reported by Dr. Grant focused on clinical outcomes at 18 months. He and his colleagues ran skin-prick testing on 186 of the 259 (72%) children in the study (the remaining children weren’t available for this follow-up assessment). They tested three aeroallergens: cat, pollen, and house dust mite. They saw no significant differences in the prevalence of positive skin-prick reactions among the three study groups to cat and pollen, but prevalence levels of positive reactions to dust mite were 9% in the controls, 3% of children in the low-dosage group, and none in the high dosage group. The difference between the controls and high dosage groups was statistically significant; the difference between the controls and the low dosage group was not significant, Dr. Grant said. Additional testing of specific IgE responses to four different dust mite antigens showed statistically significant reductions in responses to each of the four antigens among the high dosage children, compared with the controls and with the low dosage children.