Umbilikal Kord 25-Hidroksivitamin D Düzeyleri ile Term ve Miada Yakın Yenidoğanlarda Solunum Sıkıntısı Arasındaki İlişki: Prospektif Gözlemsel Bir Çalışma

Öz

Amaç: Vitamin D yetersizliği, erken başlangıçlı sepsisten solunumsal uyum bozukluklarına uzanan çeşitli yenidoğan sorunlarıyla giderek daha sık ilişkilendirilmektedir. Bu çalışmada, 34. gebelik haftası ve üzerinde doğan bebeklerde kord kanı 25-hidroksivitamin D konsantrasyonlarının solunum sıkıntısının varlığı ve şiddetiyle birlikte değişip değişmediği incelenmiştir. Gereç ve Yöntem: Gebelik yaşı ≥34 hafta olan yenidoğanlarda doğum sırasında kord kanı alındı ve lameller cisimcik sayımı (LCS) için gastrik sıvı aspire edildi. Elde edilen kord 25-OH-D konsantrasyonları ile LCS değerleri, bebeklerin gereksinim duyduğu solunum desteği düzeyiyle karşılaştırıldı. Bulgular: Doksan dokuz yenidoğan çalışmaya alındı; bunlardan 52'si (%52,5) solunum sıkıntısı nedeniyle yoğun bakıma yatırıldı. Bu bebeklerde medyan kord 25-OH-D düzeyi 5,8 (3-51,1) ng/ml iken kontrollerde 13 (2,8-23,2) ng/ml idi (p=0,043); LCS değerleri de benzer biçimde düşüktü (p=0,033). Solunum sıkıntısı grubunda 25-OH-D ile LCS arasında zayıf bir korelasyon saptandı (r=0,306, p=0,035). Buna karşılık çok değişkenli lojistik regresyonda solunum sıkıntısının bağımsız belirleyicisi yalnızca gebelik yaşı oldu (düzeltilmiş OR=0,42, %95 GA 0,23-0,79, p=0,007); vitamin D düzeyi bağımsız bir ilişki göstermedi (düzeltilmiş OR=0,95, %95 GA 0,87-1,05, p=0,32). Sonuç: Solunum sıkıntısı olan yenidoğanlarda kord 25-OH-D düzeyleri daha düşük bulunmakla birlikte, bu fark büyük ölçüde immatüriteye bağlıydı; gebelik yaşı ve doğum ağırlığı hesaba katıldığında vitamin D'nin bağımsız bir katkısı gösterilemedi. Bulgular hipotez üretici niteliktedir ve daha geniş serilerde doğrulanmayı gerektirmektedir.

Anahtar Kelimeler

• Yenidoğan
• 25-OH-Vit D
• solunum sıkıntısı
• geçici takipne.

Umbilical Cord 25-Hydroxyvitamin D Concentrations and Respiratory Distress in Term And Near-Term Newborns: A Prospective Observational Study

Öz

Objective: Vitamin D insufficiency has increasingly been implicated in neonatal conditions ranging from early-onset sepsis to disorders of respiratory adaptation. We examined whether 25-hydroxyvitamin D concentrations measured in cord blood track with the presence and severity of respiratory distress among infants born at or beyond 34 gestational weeks. Materials and Methods: Cord blood was drawn at delivery, and gastric fluid was aspirated for lamellar body counting (LBC), in newborns of ≥34 weeks' gestation. Cord 25-OH-D concentrations and LBC values were then examined against the level of respiratory support each infant required. Results: Ninety-nine newborns were enrolled, of whom 52 (52.5%) required intensive care admission because of respiratory distress. Median cord 25-OH-D reached 5.8 (3-51.1) ng/ml in these infants versus 13 (2.8-23.2) ng/ml among controls (p=0.043), and LBC values were likewise reduced (p=0.033). Within the respiratory distress group, 25-OH-D correlated weakly with LBC (r=0.306, p=0.035). On multivariable logistic regression, however, only gestational age remained an independent predictor of respiratory distress (adjusted OR=0.42, 95% CI 0.23-0.79, p=0.007), whereas vitamin D did not (adjusted OR=0.95, 95% CI 0.87-1.05, p=0.32). Conclusion: Although cord 25-OH-D was lower among newborns with respiratory distress, the difference tracked with immaturity: once gestational age and birth weight were accounted for, vitamin D carried no independent association. The findings are hypothesis-generating and require testing in larger cohorts.

Anahtar Kelimeler

• Newborn
• 25-OD-Vit D
• respiratory distress
• transient tachypnoe

Kaynakça

1. Referans 1. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 2008;87(4):1080S-6S.
2. Referans 2. Ozkan B. Nutritional rickets. J Clin Res Pediatr Endocrinol 2010; 2(4):137-43
3. Referans 3. Lykkedegn S, Sorensen GL, Beck-Nielsen SS, Christesen HT. The impact of vitamin D on fetal and neonatal lung maturation. A systematic review. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2015:308(7), L587-L602.
4. Referans 4. Evans KN, Bulmer JN, Kilby MD, Hewison M. Vitamin D and placental-decidual function. J Soc Gynecol Invest 2004; 11: 263–271.
5. Referans 5. Nguyen M, Trubert CL, Rizk-Rabin M, Rehan VK, Besancon F, Cayre YE, Garabedian M. 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. J Steroid Biochem Mol Biol. 2004: 89 –90: 93–97.
6. Referans 6. Phokela SS, Peleg S, Moya FR, Alcorn JL. Regulation of human pulmonary surfactant protein gene expression by 1α, 25-dihydroxyvitamin D3. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2005:289(4), L617-L626.
7. Referans 7. Mendelson CR. Role of transcription factors in fetal lung development and surfactant protein gene expression. Annu Rev Physiol.2000: 62: 875–915.
8. Referans 8. Liggins GC and Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics.1972: 50: 515–525.

9. Referans 9. Nguyen TM, Guillozo H, Marin L, Tordet C, Koite S, Garabedian M. Evidence for a vitamin D paracrine system regulating maturation of developing rat lung epithelium. Am J Physiol Lung Cell Mol Physiol.1996: 271: L392–L399.
10. Referans 10. Marin L, Dufour ME, Nguyen TM, Tordet C, Garabedian M. Maturational changes induced by 1 alpha,25-dihydroxyvitamin D3 in type II cells from fetal rat lung explants. Am J Physiol. 1993;265:L45-L52.
11. Referans 11. Marin L, Dufour ME, Tordet C, Nguyen M. 1,25(OH)2D3 stimulates phospholipid biosynthesis and surfactant release in fetal rat lung explants. Biol Neonate. 1990;57(3-4):257-260.
12. Referans 12. Nguyen TM, Guillozo H, Marin L, Dufour ME, Tordet C, Pike JW, Garabedian M. 1,25-Dihydroxyvitamin D3 receptors in rat lung during the perinatal period: regulation and immunohistochemical localization. Endocrinology. 1990;127(4):1755-1762.
13. Referans 13. Erenberg A, Leff RD, Haack DG, Mosdell KW, Hicks GM, Wynne BA. Caffeine citrate for the treatment of apnea of prematurity: a double-blind, placebo controlled study. Pharmacotherapy. 2000; 20(6):644–652.
14. Referans 14. Dubin SB. Characterization of amniotic fluid lamellar bodies by resistive-pulse counting: relationship to measures of fetal lung maturity. Clin Chem. 1989; 35: 612–616.
15. Referans 15. Verder H, Ebbesen F, Brandt J, Dahl M, Esberg G, Eschen C, Grytter C, et al. Lamellar body counts on gastric aspirates for prediction of respiratory distress syndrome. Acta Paediatr 2011; 100: 175–180.
16. Referans 16. Jobe AH. Surfactant in transient tachypnea of the newborn. The Journal of Pediatrics, 2011, 159.5: A3.
17. Referans 17. Machado LU, Fiori HH, Baldisserotto M, Ramos Garcia PC, Vieira AC, Fiori RM. Surfactant deficiency in transient tachypnea of the newborn. J Pediatr. 2011;159:750–4.
18. Referans 18. Silverman WA, Andersen DA. A controlled clinical trial of effects of water mist on obstructive respiratory signs, death rate and necropsy findings among premature infants. Pediatrics. 1956;17(1):1–10.
19. Referans 19. Bhan I, Powe CE, Berg AH, Ankers E, Wenger JB, Karumanchi SA, et al. Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney Int 2012;82:84–9.
20. Referans 20. Ala-houhala M, Koskinen T, Terho A, et al. Maternal compared with infant vitamin D. Archives of Disease in Childhood, 1986;61: 1159-63.
21. Referans 21. Barrett H, Mc Elduff A. Vitamin D and pregnancy: an old problem revisited. Best Pract Res Clin Endocrinol Metab 2010;24:527-39.
22. Referans 22. Andiran N, Yordam N, Ozon A. Risk Factors for Vitamin D Deficiency in Breast-fed Newborns and Their Mothers. Nutrition 2002;Volume 18, Number 1,
23. Referans 23. Gurz AA, Igde FAA, Dikici MF. Fetal and Maternal Effects of Vitamin D. Konuralp Medical Journal/Konuralp Medical Journal. 2015;7(1):69-75.
24. Referans 24. Edelson JD, Chan S, Jassal D, Post M, Tanswell KA. Vitamin D stimulates DNA synthesis in alveolar type II cells. Biochim Biophys Acta1221: 159–166, 1993.
25. Referans 25. Gaultier C, Harf A, Balmain N, Cuisinier-Gleizes P, Mathieu H. Lung mechanics in rachitic rats. Am Rev Respir Dis 130: 1108–1110,1984.
26. Referans 26. Halloran BP. Cellular growth and differentiation during embryogenesis and fetal development. The role of vitamin D. Adv Exp Med Biol 352:227–236, 1994.
27. Referans 27. Saadoon A, Ambalavanan N, Zinn K, Ashraf AP, MacEwen M, Nicola T, et al. Effect of prenatal versus postnatal vitamin D deficiency on pulmonary structure and function in mice. Am J Respir .Cell Mol Biol. 2017;56:383–92.
28. Referans 28. James DK, Chiswick ML, Harkes A, Williams M, Hallworth J. Non-specificity of surfactant deficiency in neonatal respiratory disorders. Br Med J (Clin Res Ed). 1984;288:1635–8.
29. Referans 29. Bhuta T, Kent-Biggs J, Jeffery HE. Prediction of surfactant dysfunction in term infants by the click test. Pediatr Pulmonol.1997;23:287–91.
30. Referans 30. Jain L, Eaton DC. Physiology of fetal lung fluid clearance and the effect of labor. Semin Perinatol. 2006;30:34–43.
31. Referans 31. Fiori HH, Henn R, Baldisserotto M, Bica IG, Fiori RM. Evaluation of surfactant function at birth determined by the stable microbubble test interm and near term infants with respiratory distress. Eur J Pediatr. 2004;163:443–8.
32. Referans 32. Hallman M, Feldman BH, Kirkpatrick E, Gluck L. Absence of phosphatidylglycerol (PG) in respiratory-distress syndrome in newborn. Study of the minor surfactant phospholipids in newborns. Pediatr Res. 1977;11:714–20.
33. Referans 33. Neerhof MG, Haney EI, Silver RK, Ashwood ER, Lee IS, Piazze JJ. Lamellar body counts compared with traditional phospholipid analysis as an assay for evaluating fetal lung maturity. Obstet Gynecol. 2001;97:305–9.