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RCT finds high dose vitamin D more effective than low dose at improving growth in very low birth weight preterm infants

Posted on: July 25, 2016   by  Riley Peterson & John Cannell, MD.


A recent RCT compared the effects of 400 IU/day and 1,000 IU/day vitamin D3 supplementation on very low birth weight preterm neonates.

Preterm birth is defined as being born before 37 weeks of gestation, and accounts for 5-18% of all births. Babies born preterm are at an increased risk of birth complications such as cerebral palsy, developmental delay, low birth weight, respiratory illness and mortality. Preterm birth is the number one cause of mortality in infants.

Previous studies have explored the relationship between vitamin D and preterm birth and found that vitamin D deficient mothers were at a greater risk of having a baby born before 37 weeks of gestation. A post-hoc analysis on two pregnancy cohorts found that women with vitamin D levels ≥40 ng/ml (n=233) had a 57% lower risk of preterm birth compared to those with concentrations ≤20 ng/ml (RR=0.43, 95% confidence interval (CI)=0.22,0.83).

It is important to understand that there is a relationship between maternal vitamin D levels and infant’s vitamin D levels. Vitamin D deficiency in pregnancy is strongly associated with low levels in newborns. In fact, studies have shown that newborn babies are born with just 2/3 of their mothers’ vitamin D levels.  In order for mothers to ensure that their infant receives enough vitamin D during such a critical phase of growth and development, the infant must supplement. Due to the many different recommendations for vitamin D supplementation in newborn infants, it can become difficult to determine how much vitamin D is optimum. The American Academy of Pediatrics recommends at least 400 IU of vitamin D per day; while the European Society for Pediatric Gastroenterology Hepatology and Nutrition recommends 800-1000 IU of vitamin D per day. The current study sought to provide clarity on this matter by evaluating the effects of two vitamin D supplementation dosages (400 IU/day and 1000 IU/day) on low birth weight preterm neonates.

Researchers included a total of 50 preterm, low birth weight (>1,500 g) neonates in this study. The infants were divided into two groups. Group 1 received 400 IU of vitamin D3/day, while group 2 received 1,000 IU of vitamin D3/day. Serum calcium, phosphate and 25(OH)D were measured at baseline and 6 weeks. Secondary outcomes of vitamin D supplementation, such as growth and skeletal hypomineralization, were also measured. Skeletal hypomineralization is characterized by severe mineral deficiency in the bones, which can result in weak and brittle bones. Anthropometric measurements, such as weight and head circumference, were taken daily, and bilateral wrist radiographs were administered at the 6th week to measure skeletal hypomineralization.

This is what the researchers found:

  • At baseline, 86% of the infants were considered vitamin D deficient or insufficient (<15 ng/ml and 15-20 ng/ml, respectively).
  • Group 1 did not result in any neonates achieving vitamin D sufficiency (> 32 ng/ml).
  • Mean serum 25(OH)D levels increased in both groups, but were significantly higher in group 2 (50.91 +/- 11.14 ng/ml) than group 1 (29.37 +/-11.03 ng/ml) (p<0.001).
  • Infants in group 2 had significantly higher gain in weight and length compared to group 1 (p<0.01 and p<0.02, respectively).
  • After 6 weeks, 14 neonates had mild and 1 had moderate bone hypomineralization while only 6 infants had mild hypomineralization in group 2 (p=0.01).

The researchers concluded:

“Vitamin D supplementation in a dose of 1,000 IU/day resulted in significantly higher levels of serum calcium and 25(OH)D…and better growth compared with 400 IU/day in very low birth weight preterm neonates.”

This study along with past research clearly illustrates the importance of maintaining healthy vitamin D levels during early stages of development. The researchers concluded that 1,000 IU of vitamin D3 per day was more effective in raising vitamin D levels and supporting growth among low birth weight preterm babies than 400 IU/day, the current recommended dietary allowance (RDA) for infants under the age of one year. These findings offer further evidence that the RDA is inadequate.


Peterson, R. & Cannell, JJ. RCT finds 1,000 IU of vitamin D more effective than 400 IU in very low birth weight preterm neonates. The Vitamin D Council Blog & Newsletter, 2016.


Mathur, NB. Saini, A. Mishra, TK. Assessment of Adequacy of Supplementation of Vitamin D in Very Low Birth Weight Preterm Neonates: A Randomized Controlled Trial. Tropical Pediactrics, 2016.

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