Published date: Jan 01 2025

Journal Title: International Journal of Reproductive BioMedicine

Issue title: International Journal of Reproductive BioMedicine (IJRM): Volume 22, Issue No. 11

Pages: 845 – 856

DOI: 10.18502/ijrm.v22i11.17818

Razieh Sadat TabatabaeiDepartment of Obstetrics and Gynecology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Seyed Reza MirjaliliDr_sr_mirjalili@yahoo.comMother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Atefeh AshrafiDepartment of Obstetrics and Gynecology, Shahid Beheshti Hospital, Esfahan University of Medical Sciences, Ardestan, Iran.

Farimah ShamsiDepartment of Biostatistics and Epidemiology, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Background: Osteopenia of prematurity (OP) is characterized by reduced bone mineral content, and vitamin D deficiency may worsen OP by affecting bone metabolism.

Objective: This study aimed to investigate the correlation between maternal vitamin D levels and biochemical markers related to OP. Materials and Methods: This analytical cross-sectional study, conducted at Shahid Sadoughi hospital, Yazd, Iran, from June 2022 to September 2023, included 49 pregnant women and their preterm infants. Based on the serum alkaline phosphatase and phosphorus levels of the infants at birth and 4 wk after birth, they were divided into osteopenic and non-osteopenic groups. Maternal and neonatal vitamin D and calcium levels were then compared between these groups.

Results: The mean maternal vitamin D level was 24.9 ± 15.09 ng/ml, with 36% showing deficiency. 11 neonates at 4 wk exhibited osteopenia based on phosphorus and serum alkaline phosphatase levels. Those with osteopenia had significantly lower vitamin D (p = 0.032) and calcium levels compared to non-osteopenic neonates (p = 0.043), although maternal vitamin D mean was not a significant risk factor for OP (p = 0.313).

Conclusion: The results suggest that maternal vitamin D levels do not have a significant association with the incidence of osteopenia in neonates, as the mean maternal vitamin D concentration was not identified as a risk factor for this condition. Therefore, it is recommended that future research should investigate alternative factors that may contribute to the development of osteopenia in preterm infants

Keywords: Vitamin D, Osteopenia, Prematurity, Alkaline phosphatase.

[1] Llorente-Pelayo S, Docio P, Lavín-Gómez BA, García-Unzueta MT, De Las Cuevas I, De La Rubia L, et al. Modified serum ALP values and timing of apparition of knee epiphyseal ossification centers in preterm infants with cholestasis and risk of concomitant metabolic bone disease of prematurity. Nutrients 2020; 12: 3854.

[2] Kehinde F, Marinescu A, Turchi R. Catch it before it breaks!: Managing metabolic bone disease of prematurity. Curr Opin Pediatr 2021; 33: 676–683.

[3] Panda M, McIntosh J, Chaudhari T, Kent AL. Do maternal vitamin D levels influence vitamin D levels in preterm neonates? Int J Pediatr 2019; 2019: 8613414.

[4] Pinto MRC, Machado MMT, de Azevedo DV, Correia LL, Leite ÁJM, Rocha HAL. Osteopenia of prematurity and associated nutritional factors: Case-control study. BMC Pediatr 2022; 22: 519.

[5] Dan AM, Vasilescu DI. A severe case of osteopenia of prematurity. Obstet Şi Ginecol 2022; 70: 40.

[6] Wang J, Zhao Q, Chen B, Sun J, Huang J, Meng J, et al. Risk factors for metabolic bone disease of prematurity: A meta-analysis. PLoS One 2022; 17: e0269180.

[7] Angelika D, Etika R, Mapindra MP, Utomo MT, Rahardjo P, Ugrasena IDG. Associated neonatal and maternal factors of osteopenia of prematurity in low resource setting: A cross-sectional study. Ann Med Surg (Lond) 2021; 64: 102235.

[8] Salehi M, Leung-Pineda V. Disorders of calcium and phosphate metabolism in infants and children. In: Wong EC, Dietsen DJ, Benneth MJ, Haymond S. Biochemical and molecular basis of pediatric disease. 5th Ed. USA: Academic Press; 2021; 379–410.

[9] Chacham S, Pasi R, Chegondi M, Ahmad N, Mohanty SB. Metabolic bone disease in premature neonates: An unmet challenge. J Clin Res Pediatr Endocrinol 2020; 12: 332–339.

[10] Kumar M, Ali A, Khan MA, Sohail S, Saleem SM, Khan M, et al. Relationship of caffeine regimen with osteopenia of prematurity in preterm neonates: A cohort retrospective study. BMC Pediatr 2022; 22: 437.

[11] Kavurt S, Demirel N, Yücel H, Unal S, Yıldız YT, Bas AY. Evaluation of radiologic evidence of metabolic bone disease in very low birth weight infants at fourth week of life. J Perinatol 2021; 41: 2668–2673.

[12] Simsek GK, Buyuktiryaki M, Kanmaz Kutman HG, Canpolat FE. Alkaline phosphatase levels of preterm infants under 30 weeks of gestational age and its role in the diagnosis of osteopenia of prematurity. Ann Med Res 2019; 26: 1688–1691.

[13] Kanike N, Hospattankar KG, Sharma A, Worley S, Groh-Wargo S. Prevalence of vitamin D deficiency in a large newborn cohort from Northern United States and effect of intrauterine drug exposure. Nutrients 2020; 12: 2085.

[14] Tan YL, Tsao PN, Chou HC, Yen TA, Chen CY. Hypophosphatemia as an early metabolic bone disease marker in extremely low-birth-weight infants after prolonged parenteral nutrition exposure. J Parenter Enter Nutr 2021; 45: 1268–1274.

[15] Graça MI, Silva J, Guimarães H. Metabolic bone disease of prematurity- a report of five cases. J Pediatr Neonatal Individ Med 2019; 8: e080120.

[16] Rayannavar A, Calabria AC. Screening for metabolic bone disease of prematurity. Semin Fetal Neonatal Med 2020; 25: 101086.

[17] Avila-Alvarez A, Urisarri A, Fuentes-Carballal J, Mandiá N, Sucasas-Alonso A, Couce ML. Metabolic bone disease of prematurity: Risk factors and associated short-term outcomes. Nutrients 2020; 12: 3786.

[18] Pajak A, Królak-Olejnik B, Szafranska A. Early hypophosphatemia in very low birth weight preterm infants. Adv Clin Exp Med 2018; 27: 841–847.

[19] Brener Dik PH, Galletti MF, Fernández Jonusas SA, Alonso G, Mariani GL, Fustiñana CA. Early hypophosphatemia in preterm infants receiving aggressive parenteral nutrition. J Perinatol 2015; 35: 712–715.

[20] Bradford CV, Cober MP, Miller JL. Refeeding syndrome in the neonatal intensive care unit. J Pediatr Pharmacol Ther 2021; 26: 771–782.

[21] Lü KL, Xie SS, Hu Q, Yang ZY, Fan QLI, Liu E, et al. Diagnostic markers of metabolic bone disease of prematurity in preterm infants. Bone 2023; 169: 116656.

[22] Abdallah EAA, Said RN, Mosallam DS, Moawad EMI, Kamal NM, Fathallah MGED. Serial serum alkaline phosphatase as an early biomarker for osteopenia of prematurity. Medicine (Baltimore) 2016; 95: e4837.

[23] Perrone S, Caporilli C, Grassi F, Ferrocino M, Biagi E, Dell’Orto V, et al. Prenatal and neonatal bone health: Updated review on early identification of newborns at high risk for osteopenia. Nutrients 2023; 15: 3515.

[24] O’Reilly P, Saviani M, Tou A, Tarrant A, Capra L, McCallion N. Do preterm bones still break? Incidence of rib fracture and osteopenia of prematurity in very low birth weight infants. J Paediatr Child Health 2020; 56: 959–963.

[25] Alizadeh Taheri P, Sajjadian N, Beyrami B, Shariat M. Prophylactic effect of low dose vitamin D in osteopenia of prematurity: A clinical trial study. Acta Med Iran 2014; 52: 671–674.

[26] Manish G, Uday Kumar M, Sukriti K. Prediction of rise in alkaline phosphatase at different vitamin D levels. CHRISMED J Health Res 2023; 10: 55–59.

[27] Chauhan SS, Sarkar PD, Bhimte B. Prematurity and related biochemical outcomes: Study of bone mineralization and renal function parameters in preterm infants. Biochem Res Int 2011; 2011: 740370.

[28] Malone Jenkins S, Chan G, Weaver-Lewis K, Bardsley T, Felix J, Grinsell M. Vitamin D, bone density, and nephrocalcinosis in preterm infants: A prospective study. Pediatr Nephrol 2022; 37: 1325–1332.

[29] Faienza MF, D’Amato E, Natale MP, Grano M, Chiarito M, Brunetti G, et al. Metabolic bone disease of prematurity: Diagnosis and management. Front Pediatr 2019; 7: 143.

[30] Ercan M, Ozcetin M, Karaci M, Ozgurhan G, Yasar A, Guven B. Relationship between newborn craniotabes and vitamin D status. North Clin Istanbul 2016; 3: 15–21.

[31] Kołodziejczyk A, Borszewska-Kornacka MK, Seliga-Siwecka J. Monitored supplementation of vitamin D in preterm infants (MOSVID trial): Study protocol for a randomised controlled trial. Trials 2017; 18: 424.

[32] Saleem AM, Alsayed LM, Ahmed IA, Rezk NA. Biochemical markers and radiological findings in premature osteopenic neonates. Egypt J Hosp Med 2022; 87: 2038–2045.

[33] Moon RJ, Curtis EM, Woolford SJ, Ashai S, Cooper C, Harvey NC. The importance of maternal pregnancy vitamin D for offspring bone health: Learnings from the MAVIDOS trial. Ther Adv Musculoskelet Dis 2021; 13: 1759720X211006979.