Vitamin D and bronchopulmonary dysplasia in preterm infants

Abstract

Background Vitamin D deficiency is associated with asthma and reactive airway disease in childhood but its potential contribution to bronchopulmonary dysplasia (BPD) in preterm infants is unknown. Preterm infants have lower levels of 25-hydroxyvitamin D (25[OH]D) at birth and are at risk for nutritional deficiencies after birth. Objective To evaluate the association of 25(OH) D concentrations at birth and at 36 weeks corrected gestational age with BPD in preterm infants born prior to 29 completed weeks of gestation. Methods We collected umbilical cord blood samples from 44 preterm infants (gestational age <29 weeks) delivered at Brigham and Women's Hospital in Boston. In addition, with parental consent we collected venous samples at 36 weeks corrected age from 20 preterm infants born before 29 weeks gestation (including 6 infants with previously collected cord blood). Samples were frozen at -80°C until subsequent measurement of 25(OH) D levels by chemiluminescence. We used multivariable logistic models to adjust for gestational age and considered other confounding variables including maternal race, age, mode of delivery and infant sex. Results Among 44 infants, 41 (93.2%) survived and 3 (6.8%) died before 36 weeks corrected age. Median 25(OH) D levels at birth were 30.4 ng/ml in preterm infants who subsequently died or developed BPD and 33.8 ng/ml in infants who survived without BPD (p=0.6). Median 25(OH) D levels at corrected age of 36 weeks were 59.0 ng/ml among survivors without BPD and 64.2 ng/ml among survivors with BPD (p=0.9). Neither cord blood nor 36 week corrected 25(OH) D levels were associated with odds of death or BPD (adjusted OR 1.00, 95% CI: 0.73-1.37, OR 0.93, 95% CI: 0.61-1.43 respectively). Conclusion Among this population of extremely preterm infants neither cord blood nor the 36 week corrected age 25(OH) D levels were associated with development of BPD. Notably, at the current level of supplementation, all extremely preterm infants in our cohort had achieved 25(OH) D levels >30 ng/ml by 36 weeks corrected age, which is thought to represent sufficiency in adult and pediatric populations.

Comparison of Serum Vitamin D in the Umbilical Cord of Survived with Not Survived Premature Infants

“…Even by removing the effect of intervening factors (gestational age, first minute Apgar score and fifth minute Apgar score), vitamin D deficiency could predict the death of infants, which is consistent with the study by Yang et al (27). In contrast to this, the studies by Joung et al and Onwuneme et al, showed no relationship between the risk of death among succumbed premature infants and the level of vitamin D [(OH)-D] in the umbilical cord (14,28). In these studies, all neonates had normal levels of vitamin D, but in our study, four-fifths of newborns had vitamin D deficiency.…”

“…Vitamin D affects the relationship between endodermal and mesodermal cells that results in alveolar structure and lung maturation. Deficiency of this vitamin, followed by lung non-maturation, may cause the more need for oxygen therapy (14,31).…”

“…In a study of 44 infants born before the 29th week of gestation, the average vitamin D level of the umbilical cord blood was 33.8 ng/mL in 41 survived neonates and 30.4 ng/mL in 3 dead neonates, and there was a significant difference between the two groups in the vitamin D level (14). Several studies have shown that respiratory distress, intraventricular hemorrhage, retinopathy of prematurity, and infections are more common in newborns with vitamin D deficiency (12,13).…”

“…Vitamin D deficiency is common in premature neonates (12). which can be due to maternal vitamin deficiency and causes serious problems in premature neonates, such as increased risk of respiratory problems at birth, osteopenia of prematurity, bronchopulmonary dysplasia, increased risk of infectious diseases, reduced brain growth, seizures, growth disturbances, retinopathy of immaturity, brain hemorrhage, and death (13)(14)(15). Studies report the effect of vitamin D deficiency on the regulation of immune responses by generating an antimicrobial peptide pattern in epithelial cells, neutrophils, and macrophages and the lack of lung maturation by examining the specific vitamin D receptor (VDR), which is expressed in most tissues of the body, in terms of regulation, diagnosis, and differentiation of the cell in immature died premature neonates (15)(16)(17)(18)(19)(20).…”

Nutrients and Microbiota in Lung Diseases of Prematurity: The Placenta-Gut-Lung Triangle

“…Some epidemiological studies have associated neonatal hypovitaminosis D with risk of wheezing, asthma and respiratory tract infections later in infancy [55]. A prospective observational study correlating cord blood and 36-weeks corrected age 25OH-vitD levels in extremely preterm infants with odds of BPD failed to show any association, although most enrolled subjects did not reach vitamin D insufficiency levels (30/33 ng/mL at birth in the BPD and no-BPD groups, respectively) [56]. Interestingly, a similar study conducted in another environment with low/insufficient maternal and neonatal levels yielded opposite results (i.e., a significant correlation between maternal and neonatal levels between BPD/noBPD groups (19/28 and 15/7 ng/mL, respectively) [57]).…”