Formula-fed infants receiving vitamin D supplements were found to be twice as likely as other infants to develop urinary tract infections during the first 3 months of life in a study that may have unmasked a previously overlooked association.
Dr. Robert Gensure and associates at the Ochsner Health System in New Orleans set out to study the role of vitamin D in rickets prevention in breastfed infants. Only when the first enrolled patient developed a urinary tract infection (UTI)—and the institution's safety monitoring board asked the researchers to study possible links to vitamin D—did a retrospective analysis show an unexpected, significant association between formula-fed infants receiving vitamin D supplements and UTIs.
Vitamin D supplementation was determined to significantly increase the risk of UTI in all infants in the study, with a relative risk of 1.8. Formula-fed infants accounted for this increased risk, with a relative risk of 2.2, compared with a nonsignificant relative risk in exclusively breastfed babies of 1.6, and a nonsignificant risk in mixed-fed babies of 1.1.
In the retrospective chart study of 315 infants in whom urine cultures were obtained, a higher percentage of formula-fed infants (16%, or 30 of 189) received vitamin D supplements, compared with breastfed (10%, 6 of 59) and mixed-fed (12%, or 8 of 67) infants, Dr. Ranjitha Katikaneni reported on behalf of the Ochsner team at the southern regional meeting of the American Federation for Medical Research in New Orleans.
Despite recently increasing the recommended vitamin D intake for children, the American Academy of Pediatrics does not recommend vitamin D supplementation of infants who receive at least a quart of formula per day, since commercial formulas sold in the United States all contain at least 400 IU/L of vitamin D3 (Pediatrics 2008;122:1142–52).
Still, many parents may hear reports about babies needing more vitamin D than previously believed and decide to buy over-the-counter supplement drops, Dr. Gensure said in an interview.
“Greater caution needs to be used,” he said. “The idea that vitamin D should be taken carte blanche, as much as you want, may not be true, especially in infants.” Until more research can be done on possible associations between vitamin D supplementation and UTIs in formula-fed infants, he urged pediatricians to stress to parents that only breastfed infants need supplementation.
Another finding in the Ochsner study was that breastfeeding was not protective against UTIs. Elevated UTI risk in formula-fed infants may, in fact, have confounded earlier studies by making it appear that breastfeeding was protective.
Although UTIs are the most common serious bacterial infection in infants, they are still rare events, making a national study difficult, explained Dr. Gensure, section chief of pediatric endocrinology at Ochsner and principal investigator for pediatric endocrine research. However, any major institution could replicate the Ochsner study by retrospectively studying a set number of charts in which UTI was diagnosed to see what percentage of the infants were receiving vitamin D supplementation along with formula.
In case reports involving older children, hypervitaminosis D has been associated with urinary tract infections and one case report linked vitamin D intoxication in a 4-month-old to nephrocalcinosis without renal impairment. Lower level vitamin D supplementation in infants has not been reported previously to have an association with UTI. The Ochsner team postulated that vitamin D supplementation in infants might lead to a milder form of nephrocalcinosis than that seen with hypervitaminosis D, “which could in turn serve as a nidus for bacterial seeding.” Further, derivatives of vitamin D may suppress immune response in infants, allowing infections to proliferate.
Tulasi Ponnapakkam, Ph.D., a study co-author, said UTI incidence will be studied in an ongoing prospective trial evaluating different levels of vitamin D supplementation in 450 newborns receiving formula and breast milk. Both studies are supported by the Gerber Foundation, which manufactures infant formula and vitamin supplementation for infants.
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