Comparison of 25- Hydroxy Vitamin D Levels in Premature Infants with and without Respiratory Distress

Document Type: Original Article


1 Department of Pediatrics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Pediatrics Endocrinology, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

3 Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran


Background: The 25-hydroxyvitamin D3(25-OH D3)deficiency is a common problem worldwide, and it is aprevalent incidence in neonates. Different studies investigated the relationship of vitamin D deficiency with neonatal mortality and morbidity. This study aimed to evaluate the relationship between vitamin D deficiency and respiratory distress in preterm neonates.
Methods: A prospective cohort study was conducted in Alzahra Hospital affiliated to Isfahan University of Medical Sciences, Isfahan, Iran. In total, 160 preterm neonates with>1000 g birth weight were evaluated for the manifestation of respiratory distress during the first 6 h of life. The neonates were divided into two groups of A (n=80) with respiratory symptoms and B (n=80) without respiratory symptoms. The level of 25-OH D3 was measured in the first h of the neonate's life. All neonates were followed to reach 36 weeks of gestational age or 28th day of life. Subsequently, the two groups were compared in terms of vitamin D levels. There was a relationship between vitamin D deficiency and respiratory morbidities in group A.
Results: The mean vitamin D level was obtained at 27.42±11.25 ng/mL, and it was categorized into adequate level (n=53, 33.1%), inadequate level (n=62,38.8%), and vitamin D deficiency (n=45, 28.1%).According to the results, vitamin D level correlated significantly with birth weight and gestational age (P<0.05). Moreover, respiratory distress correlated with birth weight, gestational age, and the use of corticosteroids during pregnancy (P<0.001). The mean vitamin D level in group A (with respiratory distress syndrome [RDS]) was significantly lower than that in group B (without RDS, P<0.001).Furthermore, vitamin Dcorrelated with RDS, a need for intubation surfactant extubation, and duration of continuous positive airway pressure (P<0.05).
Conclusion: Neonates with a low level of vitamin D are prone to manifest respiratory distress, and vitamin D deficiency is a risk factor for presenting RDS.


1. Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, et al. DCs metabolize sunlight-induced vitamin D3 to'program'T cell attraction to the epidermal chemokine CCL27. NatImmunol. 2007; 8(3):285-93.
2. Di Rosa M, Malaguarnera M, Nicoletti F, Malaguarnera L. Vitamin D3: a helpful immuno‐modulator. Immunology. 2011;134(2):123-39.
3. Berry DJ, Vimaleswaran KS, Whittaker JC, Hingorani AD, Hyppönen E. Evaluation of genetic markers as instruments for Mendelian randomization studies on vitamin D. PloS One. 2012;7(5):e37465.
4. Kesby JP, Cui X, Ko P, McGrath JJ, Burne TH, Eyles DW. Developmental vitamin D deficiency alters dopamine turnover in neonatal rat forebrain. NeurosciLett. 2009;461(2):155-8.
5. Fares S, Sethom MM, Khouaja-Mokrani C, Jabnoun S, Feki M, Kaabachi N. Vitamin A, E, and D deficiencies in tunisian very low birth weight neonates: prevalence and risk factors. PediatrNeonatol. 2014;55(3):196-201.
6. Sachan A, Gupta R, Das V, Agarwal A, Awasthi PK, Bhatia V. High prevalence of vitamin D deficiency among pregnant women and their newborns in northern India. AmJClin Nutr. 2005;81(5):1060-4.
7. Newhook LA, Sloka S, Grant M, Randell E, Kovacs CS, Twells LK. Vitamin D insufficiency common in newborns, children and pregnant women living in Newfoundland and Labrador, Canada. MaternChild Nutr. 2009;5(2):186-91.
8. Brown AJ, Dusso AS, Slatopolsky E. Vitamin D analogues for secondary hyperparathyroidism. Nephrol DialTransplant. 2002;17(Suppl10):10-9.
9. Darlow BA, Graham P, Rojas‐Reyes MX. Vitamin A supplementation to prevent mortality and short‐and long‐term morbidity in very low birth weight infants. Cochrane Database Syst Rev. 2016; 8:CD000501.
10. Karatekin G, Kaya A, Salihoğlu Ö, Balci H, Nuhoğlu A. Association of subclinical vitamin D deficiency in newborns with acute lower respiratory infection and their mothers. EurJClin Nutr. 2009;63(4):473-7.
11. Wang TJ, Zhang F, Richards JB, Kestenbaum B, Van Meurs JB, Berry D, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010;376(9736): 180-8.
12. Ataseven F, Aygün C, Okuyucu A, Bedir A, Kücük Y, Kücüködük S. Is vitamin D deficiency a risk factor for respiratory distress syndrome. Int J Vitam Nutr Res. 2013;83(4):232-7.
13. Cetinkaya M, Cekmez F, Buyukkale G, Erener-Ercan T, Demir F, Tunc T, et al. Lower vitamin D levels are associated with increased risk of early-onset neonatal sepsis in term infants. JPerinatol. 2015;35(1):39-45.
14. Cetinkaya M, Erener-Ercan T, Kalayci-Oral T, Babayiğit A, Cebeci B, Semerci S, et al.Maternal/neonatal vitamin D deficiency: a new risk factor for necrotizing enterocolitis in preterm infants? J Perinatol. 2017;37(6):673-8.

15. Joung KE, Burris HH, Van Marter LJ, McElrath TF, Michael Z, Tabatabai P, et al. Vitamin D and bronchopulmonary dysplasia in preterm infants. JPerinatol. 2016;36(10):878-82.
16. Levine CR, Gewolb IH, Allen K, Welch RW, Melby JM, Pollack S, et al. Safety, pharmacokinetics, and anti-inflammatory effects of intratracheal recombinant human Clara cell protein in premature infants with respiratory distress syndrome. PediatrRes. 2005; 58(1):15-21.
17. Cetinkaya M, Cekmez F, Erener-Ercan T, Buyukkale G, Demirhan A, Aydemir G, et al. Maternal/neonatal vitamin D deficiency: a risk factor for bronchopulmonary dysplasia in preterms? J Perinatol. 2015;35(10):813-7.
18. Kim I, Kim SS, Song JI, Yoon SH, Park GY, Lee YW. Association between vitamin D level at birth and respiratory morbidities in very-low-birth-weight infants. J Korean Pediatr. 2019;62(5):166-72.
19. Maghbooli Z, Hossein-Nezhad A, Shafaei AR, Karimi F, Madani FS, Larijani B. Vitamin D status in mothers and their newborns in Iran. BMC Pregnancy Childbirth. 2007;7(1):1.
20. De‐Regil LM, Palacios C, Lombardo LK, Peña‐Rosas JP. Vitamin D supplementation for women during pregnancy. Sao Paulo Med J. 2016; 134(3):274-5.
21. Shin YH, Yu J, Kim KW, Ahn K, Hong SA, Lee E, et al. Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA). Korean J Pediatr. 2013;56(10):439-45.
22. de Haan K, Groeneveld AJ, de Geus HR, Egal M, Struijs A. Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis. CritCare. 2014;18(6):660.
23. Morgan C, Dodds L, Langille DB, Weiler HA, Armson BA, Forest JC, et al. Cord blood vitamin D status and neonatal outcomes in a birth cohort in Quebec, Canada. ArchGynecolObstet. 2016;293(4):731-8.
24. Camargo CA, Ingham T, Wickens K, Thadhani R, Silvers KM, Epton MJ, et al. Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics. 2011;127(1):e180-7.
25. Marshall I, Mehta R, Petrova A. Vitamin D in the maternal–fetal–neonatal interface: clinical implications and requirements for supplementation. J Matern Fetal Neonatal Med. 2013;26(7):633-8.
26. Torday JS, Rehan VK. A cell–molecular approach predicts vertebrate evolution. MolBiolEvol. 2011; 28(11):2973-81.
27. Bossé Y, Lemire M, Poon AH, Daley D, He JQ, Sandford A, et al. Asthma and genes encoding
components of the vitamin D pathway. RespirRes. 2009;10(1):98.
28. Kho AT, Bhattacharya S, Tantisira KG, Carey VJ, Gaedigk R, Leeder JS, et al. Transcriptomic analysis of human lung development. AmJRespirCrit Care Med. 2010;181(1):54-63.
29. Marin L, Dufour M, Tordet C, Nguyen M. 1, 25 (OH) 2D3 stimulates phospholipid biosynthesis and surfactant release in fetal rat lung explants. Biol Neonatol. 1990;57(3-4):257-60.
30. Nguyen M, Trubert C, Rizk-Rabin M, Rehan V, Besancon F, Cayre Y, et al. 1, 25-Dihydroxyvitamin D3 and fetal lung maturation: immunogold detection of VDR expression in pneumocytes type II cells and effect on fructose 1, 6 bisphosphatase. JSteroid BiochemMol Biol. 2004;89-90(1-5):93-7.
31. Sakurai R, Shin E, Fonseca S, Sakurai T, Litonjua AA, Weiss ST, et al. 1α, 25 (OH) 2D3 and its 3-epimer promote rat lung alveolar epithelial-mesenchymal interactions and inhibit lipofibroblast apoptosis. Am JPhysiol Lung CellMol Physiol. 2009;297(3):L496-505.
32. Clancy N, Onwuneme C, Carroll A, McCarthy R, McKenna MJ, Murphy N, et al. Vitamin D and neonatal immune function. J Matern Fetal Neonatal Med. 2013; 26(7):639-46.
33. Kempker JA, Han JE, Tangpricha V, Ziegler TR, Martin GS. Vitamin D and sepsis: an emerging relationship. Dermatoendocrinol. 2012;4(2):101-8.
34. Gniadecki R, Gajkowska B, Hansen M. 1,25-dihydroxyvitamin D3 stimulates the assembly of adherens junctions in keratinocytes: involvement of protein kinase C. Endocrinology. 1997;138(6):2241-8.
35. Sadeghi K, Wessner B, Laggner U, Ploder M, Tamandl D, Friedl J, et al. Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol. 2006;36(2):361-70.
36. Youssef DA, Miller CW, El-Abbassi AM, Cutchins DC, Cutchins C, Grant WB, et al. Antimicrobial implications of vitamin D. Dermatoendocrinol. 2011;3(4):220-9.
37. Boskabadi H, Mamoori G, Khatami SF, Faramarzi R. Serum level of vitamin D in preterm infants and its association with premature-related respiratory complications: a case-control study. Electron Physician. 2018;10(1):6208-14.
38. Boskabadi H, Zakerihamidi M, Faramarzi R. The vitamin D level in umbilical cord blood in premature infants with or without intra-ventricular hemorrhage: a cross-sectional study. Int J Reprod Biomed. 2018;16(7):429-34.
39. Boskabadi H, Maamouri G, Hemmatipour A, Parvini Z, Ramazani A, Bagheri F. Comparison of serum vitamin D in the umbilical cord of survived with not survived premature infants. Iran J Pediatr. 2019; 29(3):e84798.