Preterm infants may need 800 IU of vitamin D3 per day
Preterm infants may need to be given 800 international units (IU) of vitamin D a day to ensure they develop strong bones, according to a study to be presented Sunday, May 5, at the Pediatric Academic Societies (PAS) annual meeting in Washington, DC.
Preemies are known to be at risk for vitamin D insufficiency. If levels of vitamin D are too low, infants and children can get rickets, which leads to softening and weakening of the bones.
Recommendations from medical organizations on how much vitamin D should be given to preemies range from 400 IU to 1000 IU per day. This lack of consensus prompted researchers from All India Institute of Medical Sciences, New Delhi, to conduct the largest study to date on vitamin D supplementation in preterm infants.
Subjects included 96 infants born between 28 and 34 weeks’ gestation who were receiving milk feeding. Blood samples were taken from the infants to determine their serum vitamin D levels. The infants then were randomly assigned to receive either 800 IU or 400 IU of oral vitamin D3. Neither the parents nor the primary investigator was aware of which dose the infants were receiving.
Researchers compared whether the prevalence of vitamin D insufficiency (VDI) at 40 weeks and at 3 months corrected age differed between the groups. They also looked at whether infants with higher vitamin D levels also had stronger bones at 3 months corrected age and whether supplementation led to vitamin D levels that were too high.
Results showed that VDI was common in both groups before they received supplements (79 percent of the 800 IU group and 83 percent of the 400 IU group).
After supplementation, the prevalence of VDI at 40 weeks was 43 percent lower in the 800 IU group than the 400 IU group (38 percent vs. 67 percent). In addition, VDI was significantly lower in the 800 IU group when the infants were 3 months old (12 percent vs. 35 percent).
Vitamin D supplementation is recommended for preterm infants both while they are still in the hospital and after discharge, according to dietary guidelines issued in a clinical report published online April 29 in Pediatrics. Calcium and phosphorous supplementation is also recommended early on.
Steven A. Abrams, MD, professor of pediatrics at Baylor College of Medicine in Houston, Texas, developed the guidelines along with the American Academy of Pediatrics Committee on Nutrition.
The guidelines contain the first dietary recommendations for vitamin D and calcium intakes specifically designed for preterm infants, who “have unique bone mineral requirements that may not be assumed to be similar to those of full-term newborn infants,” the authors write. Institute of Medicine dietary guidelines issued in 2011 for calcium and vitamin D intake did not include recommendations for preterm infants.
Key elements to help prevent rickets in very low birth weight (VLBW) infants are absorbed calcium and phosphorous, the authors write, and unfortified human milk, parenteral nutrition, and infant formulas do not contain enough of these minerals to promote healthy bones in these infants. Vitamin D helps the infants absorb calcium.
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Pediatrics. Published online April 29, 2013.
Four infants needed to be supplemented with 800 IU daily to reduce one case of vitamin D insufficiency, said lead author Chandra Kumar Natarajan, DM.
“The study results show conclusively that in preterm infants with high rates of vitamin D insufficiency at baseline, supplementation with 800 IU of vitamin D3 per day compared to 400 IU per day reduces vitamin D insufficiency at term equivalent age and at 3 months,” Dr. Natarajan said. “There also is a trend toward a decrease in the prevalence of vitamin D insufficiency even in the 400 IU group at 3 months. Therefore, 400 IU per day may be sufficient after 3 months.”
Despite significant improvement in serum vitamin D levels in the 800 IU group, higher levels did not result in better bone mineralization at 3 months of age as measured by dual energy X-ray absorptiometry (DEXA). In addition, weight, length and head circumference did not differ significantly between the groups.
To prevent rickets in preterm infants, the guidelines recommend that high amounts of mineral supplements be used with infants who weigh less than 1800 to 2000 g (almost 4 - 4.5 pounds). Supplementation should include human milk fortified with minerals or formulas designed specifically for preterm infants and should be based on infant weight rather than gestational age.
For vitamin D supplementation, the authors write: “On the basis of limited data, a vitamin D intake of 200 to 400 IU/day for VLBW infants is recommended. This intake should be increased to 400 IU/day when weight exceeds ~1500 g [about 3.5 pounds] and the infant is tolerating full enteral nutrition.”
Decreasing mineral supplementation may begin after the infant weighs about 4.5 pounds, and infants with that weight “generally do well with exclusive breastfeeding or routine infant formula after discharge from the hospital,” the authors write. Vitamin D supplementation after discharge could ensure that infants receive at least 400 IU/day.
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Pediatrics. Published online April 29, 2013.
Dr. Natarajan also noted that one infant in the 800 IU group had vitamin D levels that were higher than recommended levels at 3 months of age despite the levels at term age being normal. Excess vitamin D for at least one month can cause decreased muscle tone, decreased appetite, irritability and constipation, among other problems. The infant did not experience any major effects.
“The incidence of vitamin D excess in the 800 IU group may indicate the need for monitoring vitamin D levels in infants on vitamin D supplementation, but we need larger studies to answer this,” he said. “Similarly, larger studies with longer duration of follow-up may be needed to find out any meaningful difference in clinical outcomes such as bone mineralization.”
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To view the abstract, “Daily Vitamin D Supplementation with 800 IU vs. 400 IU in Preterm Infants: A Randomized Trial,” go to http://www.abstracts2view.com/pas/view.php?nu=PAS13L1_2183.8.
“Vitamin D deficiency in pregnancy is a global health problem, and the amount of supplementation to prevent deficiency and insufficiency is controversial,” says Adekunle Dawodu, MD, a physician in the division of Global Health at Cincinnati Children’s who took part in both of the new studies. “The Institute of Medicine recommends 600 IU (International Units) daily in pregnant and lactating women. But we found that 2000 to 4000 IU a day appears to be safe in pregnant women, and 4000 IU a day is most effective in achieving optimal vitamin D levels in mothers and their infants.”
The first Cincinnati Children’s study looked at 120 preterm infants at three newborn intensive care units in the United States. Approximately two-thirds were vitamin D deficient at birth, using the standard test for measuring vitamin D levels in individuals. At current recommended levels of supplementation of vitamin D, about 40 percent remained deficient at four weeks chronological age and what would have been the 36th week of pregnancy.
The second study was conducted in the United Arab Emirates, where there is endemic vitamin D deficiency in women, in part due to the hijab – a dress practice that emphasizes modesty and thus prevents skin exposure to sun. Nearly 200 Arab women enrolled in the study, which was intended to determine the safety and effectiveness of differing level of maternal vitamin D supplementation. Supplementation of 4000 IU a day was most effective in preventing vitamin D deficiency in both mothers and their infants.
The researchers believe this finding would apply to other populations where vitamin D deficiency is endemic.
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Cincinnati Children’s Hospital Medical Center
The Pediatric Academic Societies (PAS) are four individual pediatric organizations that co-sponsor the PAS Annual Meeting – the American Pediatric Society, the Society for Pediatric Research, the Academic Pediatric Association, and the American Academy of Pediatrics. Members of these organizations are pediatricians and other health care providers who are practicing in the research, academic and clinical arenas. The four sponsoring organizations are leaders in the advancement of pediatric research and child advocacy within pediatrics, and all share a common mission of fostering the health and well-being of children worldwide.
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Debbie Jacobson
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American Academy of Pediatrics