Daily supplementation helps normalize vitamin D status in very preterm infants

3 hours ago
Stephen Padilla
Stephen PadillaSenior Editor; MIMS
Stephen Padilla
Stephen Padilla Senior Editor; MIMS
Daily supplementation helps normalize vitamin D status in very preterm infants

Very preterm infants are at increased risk of vitamin D deficiency (VDD), defined as 25(OH)D <20 ng/mL, a Thai study has found.

However, daily supplementation at <400 IU/kg results in normal vitamin D status by 8 weeks, while higher doses elevate the risk of exceeding 25(OH)D levels (>100 ng/mL) without additional benefits.

“Although this dosing appears for most infants, individualized monitoring of serum 25(OH)D remains essential to optimize vitamin D status while avoiding both deficiency and excess,” the investigators said.

A total of 126 infants born at <32 weeks’ gestation or with birth weight <1,500 g were included in this prospective cohort study. Infants were categorized by total intake (parenteral plus enteral) during weeks 0‒4, or >700 IU/kg/day. Vitamin D supplementation adhered to institutional policy.

The researchers measured serum 25(OH)D at birth, 4, and 8 weeks. They also performed biochemical markers and metabolic bone disease (MBD) screening.

Most of the infants (mean gestational age 30 weeks, mean birth weight 1,230 g) had VDD at birth (94.3 percent). VDD persisted in 17.8 percent of infants receiving <400 IU/kg/day and 6.5 percent of those receiving 400‒700 IU/kg/day at week 4, while vitamin D excess (VDE) occurred in 3.3 percent and 3.2 percent, respectively. [Eur J Clin Nutr 2026;80:694-699]

At week 8, nine in 10 infants (90.1 percent) receiving <400 IU/kg/day and nearly eight in 10 (77.4 percent) of those receiving 400‒700 IU/kg/day reached normal 25(OH)D levels, while VDE occurred in 8.6 percent and 22.6 percent, respectively. Furthermore, biochemical markers remained normal, and MBD developed in only one infant.

Transplacental transfer

The high prevalence of VDD in very preterm infants is driven by the limited foetal accrual of vitamin D due to inadequate third-trimester transplacental transfer, according to the investigators.

“In our cohort, 94.3 percent had VDD at birth, and 69.1 percent met criteria for severe VDD, exceeding the 40 percent to 80 percent reported in international cohorts,” they said. [J Perinatol 2022;42:209-216; PLoS ONE 2017;12:e0185950; Korean J Pediatr 2019;62:166-172; J Pediatr Endocrinol Metab 2020;33:1273-1281]

Median cord blood was 25(OH)D was 9.7 ng/mL, lower than those reported in Thailand and in international studies. [Nutrients 2025;17:1888]

“Because cord blood 25(OH)D strongly correlates with maternal vitamin D status, these findings underscore that maternal VDD remains a major concern in tropical Thailand,” the investigators said. [Matern Child Nutr 2021;17:e13028; BMC Pregnancy Childbirth 2018;18:412]

Recommendations

Variations exist regarding recommendations for vitamin D supplementation in very preterm infants, with ranges of 200‒400 IU/day (fixed dose) to 400‒700 IU/kg/day (weight-based). [J Pediatr Gastroenterol Nutr 2023;76:248-268; Pediatrics 2013;131:e1676-e1683]

In the US, a national survey of academic and level IV neonatal intensive care units underscored practice variations for extremely preterm infants, with most units administering 400 IU/day. [Pediatr Res 2025;97:1009-1015]

“We initially followed the earlier AAP guideline of 400 IU/day for very preterm infants,” the investigators said. “After ESPGHAN updated its recommendations, we adopted an individualized approach that allows attending neonatologists to adjust dosing based on serial serum 25(OH)D concentrations from cord blood and at 4 and 8 weeks.”