ORIGINAL RESEARCH article
Front. Pediatr.
Sec. Neonatology
This article is part of the Research TopicConsequences and Potential Pathophysiology of Perinatal Complications on Development and Maturation – Special Emphasis on Preterm BirthView all articles
Metabolic Bone Disease in Extremely Preterm Infants: Incidence, Risk Factors, and Outcomes from a Structured Bone Health Program
Provisionally accepted
Saif Alsaif1,2,3Mohanned Alrahili1,3
Talal Aljarbou1,3Lina Alsherbini1Mohammad Maghoula1Alanoud Alluwaymi1Mesaed Alsenani1Abdulrahman Altuwaym1Faisal Alamer1Abdulrahman Mandurah1Beverly Baylon1Ibrahim Ali1,3
Kamal Ali1,2,3*- 1King Abdulaziz Medical City, Riyadh, Saudi Arabia
- 2King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- 3King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
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Background: Metabolic bone disease (MBD) of prematurity is common in extremely preterm infants, yet regional data from the Middle East are limited. We evaluated incidence, risk factors, biochemical markers, and outcomes of MBD in infants <28 weeks' gestation and <1000 g. Methods: Retrospective cohort of 487 inborn preterm infants admitted to a tertiary NICU (Riyadh, Saudi Arabia; 2017–2024). MBD was defined as PTH >18 pmol/L at 4 weeks; ROC against radiographic osteopenia showed good discrimination (AUC 0.78). Clinical characteristics, nutrient intake, growth, and biochemical markers (ALP, phosphate, calcium, vitamin D, PTH) were analyzed. Logistic regression identified predictors and associations with adverse outcomes. Results: MBD was diagnosed in 202/487 infants (41.5%). Compared with non-MBD infants, those with MBD had lower GA and birthweight (both p<0.001), more postnatal steroid exposure (44% vs 27%, p<0.001), longer diuretic therapy (12% vs 3.5%, p<0.001), and TPN beyond 28 days (50% vs 31%, p<0.001). PTH and ALP were higher, while vitamin D, calcium, and magnesium were lower (all p<0.01). Despite similar calcium/phosphate intakes, MBD was associated with postnatal growth failure (77% vs 64%, p=0.005), hospitalization >60 days (88% vs 70%, p<0.001), and discharge on mineral supplements (36% vs 16%, p<0.001). Radiologic osteopenia occurred in 17.3% of MBD infants (7.1% overall); fractures were uncommon (1.8% overall; 4.4% in MBD). On multivariable analysis, MBD independently predicted fractures (aOR 8.3, 95% CI 1.01–68.3), prolonged hospitalization (aOR 1.9, 95% CI 1.09–3.29), and growth failure (aOR 1.63, 95% CI 1.06–2.53). Discussion: Within this <28-week cohort, skeletal complications were less frequent than many reports, plausibly reflecting a structured bone-health program (routine biochemical screening, optimized mineral delivery, minimal handling). Findings support incorporating PTH alongside ALP for earlier detection and point to modifiable exposures (prolonged TPN, diuretics, steroids) as targets for prevention. Prospective multicenter validation with standardized thresholds and imaging strategies is warranted. Conclusion: MBD is frequent in extremely preterm infants and is associated with growth failure and prolonged hospitalization. A 4-week PTH screen showed good discrimination for radiologic osteopenia , supporting its role within structured bone-health care. Findings are based on a biochemical definition, and diagnostic thresholds require external validation.
Keywords: metabolic, Bone, Disease, prematurity, Outcome
Received: 30 Jul 2025; Accepted: 05 Nov 2025.
Copyright: © 2025 Alsaif, Alrahili, Aljarbou, Alsherbini, Maghoula, Alluwaymi, Alsenani, Altuwaym, Alamer, Mandurah, Baylon, Ali and Ali. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kamal Ali, alika@ngha.med.sa
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