Dr. Henrik Christesen and colleagues of the Hans Christian Andersen Children’s Hospital, Odense University, Denmark have written an alarming meta-analysis of the likely role vitamin D plays in respiratory distress syndrome (RDS) in newborns. This paper provides further support for the crucial role of vitamin D in human growth and development.
The authors point out that human lung development begins in the fifth fetal week and continues until the child is approximately 8 years of age. However, RDS develops in many infants less than 34 weeks gestation due to a lack of nature’s lung lubricant, surfactant. RDS develops in about 1% of all newborn infants and is the leading cause of death in preterm infants. The incidence decreases with advancing gestational age, from about 50% in babies born at 26–28 weeks, to about 25% at 30–31 weeks.
RDS used to be fatal in many cases. In 1963, Patrick Bouvier Kennedy, son of President John F. Kennedy and First Lady Jacqueline Kennedy, died of RDS two days after his premature birth at 34 weeks gestation. Due to the rapid progression of medicine, the mortality rate for infants at 27 weeks gestation is less than 10%.
The most dramatic improvement in the treatment of infantile RDS was introduced in the early 1990s with the administration of topical surfactant therapy (the premature infant was intubated and surfactant was inhaled into the infant’s lung). This led to decreased mortality and morbidity and allowed younger and younger premature infants to survive.
Despite improved treatment, RDS continues to be a severe, high-mortality disease in infants. In survivors, RDS may be complicated by broncho-pulmonary dysplasia (BPD), a chronic lung disease characterized by impaired alveolar (air-sac) development and inflammation. The current RDS therapy with inhaled topical surfactant is expensive and as exogenous surfactant does not increase the local surfactant production, repeated administration of topical surfactant (intubation) is needed until the infant is old enough to finally make enough of its own surfactant.
As you might suspect, vitamin D is intimately involved in the growth and development of fetal lung including surfactant production. Taking the knowledge of a potential role of vitamin D in lung development and maturation into account, the authors raised the hypothesis that infantile vitamin D deficiency could be a frequent, yet largely unrecognized and modifiable risk factor of RDS and BPD in premature neonates. Therefore, they systematically reviewed the published evidence on the impact of vitamin D on lung development and maturation including synthesis of surfactant, as well as the impact on the development of RDS and BPD. They reviewed all of the human, animal and test tube studies they could find.
Only one randomized controlled trial was found and it was about bone development. In 1999 Backström et al. randomized 39 premature infants born before 33rd gestational week to vitamin D 200 IU/kg/day (maximum 400 IU/day) (low dose) or 960 IU/day (high dose) until three months of age. At birth, the mean serum 25(OH)D concentrations in both groups were 12 ng/ml. At six weeks of age, 25(OH)D was significantly higher in the high dose vitamin D group (mean 25 ng/ml vs. 18 ng/ml). The authors focused on infant bone mineralization, but noted the only significant finding was a reduced need for assisted ventilation in the infants on high dose vitamin D group (median 0 vs. 4 days, p=0.01). Moreover, a trend towards a lower duration of oxygen supplementation was recorded (median 2 vs. 14 days, p=0.06). Respiratory acidosis was more prevalent in the low vitamin D dose group as well.
In a cohort study, the researchers found that 28% of the infants with 25(OH)D <10 ng/ml had RDS compared to 14% of the infants with higher 25(OH)D. RDS was reduced 3.34 times in newborns with higher vitamin D levels.
The researchers also reviewed the ten animal studies they found. All ten studies supported the hypothesis that infantile vitamin D deficiency makes RDS and BPD worse. The multiple test tube studies all supported the thesis.
The authors concluded,
“Their data gives support to a hypothesis of vitamin D deficiency or insufficiency as a frequent, modifiable risk factor of RDS and BPD, which should be investigated in cohorts or case control studied and tested in RCTs on pregnant women, especially with threatening preterm delivery, or in the preterm neonates themselves.”
My recommendation is that all pregnant women take at least 5,000 IU/day of vitamin D (10,000 IU/day is probably better) and all premature infants be placed on 2,000 IU/day of vitamin D.
Citation of article
Cannell, J. The role of vitamin D in respiratory distress among newborns. Vitamin D Council Newsletter, 2015.
Lykkedegn S, Sorensen GL, Beck-Nielsen SS, Christesen HT. The impact of vitamin D on fetal and neonatal lung maturation. A systematic review. Am J Physiol Lung Cell Mol Physiol. 2015 Apr 1;308(7):L587-602.