Association between Vitamin D Level at Birth and Respiratory Morbidities in Very-Low-Birth-Weight Infants

Introduction: Vitamin D is a fat-soluble vitamin that plays a major role in calcium and phosphorus homeostasis and bone metabolism in the body. It is involved in innate and acquired immune responses, autoimmune responses, and suppression of cancer cell proliferation. Additionally, vitamin D regulates cardiovascular function and hormones such as insulin. It is also suspected that vitamin D is involved in embryogenesis, cell growth, and differentiation. In terms of respiratory development, type II alveolar cells express vitamin D receptor and stimulate the synthesis and secretion of surfactant in response to vitamin D. The role of vitamin D in pulmonary development, maturation, and postnatal respiratory disease has become a new field of study. The association between vitamin D deficiency and preterm diseases such as sepsis, necrotizing enterocolitis, respiratory distress syndrome (RDS), and bronchopulmonary dysplasia (BPD) is under study. Fetus does not produce vitamin D and relies on transplacental passages. In case of very-low-birth-weight (VLBW) infants, vitamin D deficiency is more common because of the short gestational period, delays in enteral nutrition, and inability to be exposed to sunlight during neonatal intensive care unit hospitalization. To the best of our knowledge, no study has reported the association between vitamin D levels at birth and respiratory morbidities in VLBW infants in Korea. In this study, we investigated the incidence and demographic differences of preterm respiratory morbidities according to vitamin D levels at birth ([Table 1]).

Materials and Methods: A retrospective study was conducted in the Soon Chun Hyang University, Bucheon Hospital (South Korea) from November 2013 to November 2017. We collected blood samples on the first day of life from 230 VLBW infants. They were then followed up for detection and reporting of respiratory morbidities. Patients who were (1) transferred to other hospitals (n = 19); (2) died before 36 weeks’ gestational age (n = 18); or (3) whose blood samples were not collected immediately after birth (n = 5) were excluded. VLBW infants with different 25 (OH) D levels were compared with regard to demographic features, maternal diseases, respiratory morbidities, and other neonatal diseases.

Results and Discussion: A total of 188 patients were enrolled. The mean serum 25(OH) D level at birth was 13.4 ± 9.3 ng/mL. The incidence of vitamin D deficiency ( < 20 ng/mL) was 79.8%, and 44.1% of preterm infants had severe vitamin D deficiency ( < 10 ng/mL). Out of the 188 preterm infants, 133 (70.7%) developed RDS and 55 (29.3%) developed BPD. Logistic analysis showed that low serum 25(OH) D level ( < 20 ng/mL) was an independent risk factor for RDS (odds ratio [OR]: 4.87, p  <  0.0001) BPD (OR: 6.19, p = 0.004), pulmonary hemorrhage (OR: 3.91, p  <  0.0001), and retinopathy of prematurity (OR: 6.11, p = 0.016) ([Table 2]).

Conclusion: Our study shows that the occurrence of vitamin D deficiency at birth in preterm, VLBW infants is extremely high, affecting around four out of five such preterm infants. Moreover, a low vitamin D status looks associated with the occurrence of respiratory morbidities in such population; however, the nature of this association needs further elucidation ([Table 3]). A limitation of our study is the small study sample; nonetheless, our findings warrant additional studies on the association between vitamin D level and neonatal morbidities.

Keywords: 25-hydroxyvitamin D, very-low-birth-weight, vitamin D deficiency, respiratory distress syndrome, bronchopulmonary dysplasia

Table 1 Patient demographics

Table 2 Clinical outcomes in the preterm infants

Table 3 Logistic regression analysis of vitamin D levels for neonatal diseases