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Metabolic bone disease in extremely preterm infants: incidence, risk factors, and outcomes from a structured bone
Saif Alsaif1,2,3, Mohanned Alrahili1,3, Talal Aljarbou1
1Neonatal Intensive Care Department, King Abdulaziz Medical City-Riyadh, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
Insights
Metabolic bone disease (MBD) is common in extremely preterm infants, leading to growth failure and longer hospital stays. Early detection using parathyroid hormone (PTH) screening can improve outcomes in neonatal intensive care units.
Area of Science:
- Neonatology
- Pediatric Endocrinology
- Bone Metabolism
Background:
- Metabolic bone disease (MBD) of prematurity is a significant concern for extremely preterm and extremely low-birth-weight (ELBW) infants.
- Limited regional data exists for MBD in the Middle East, necessitating localized studies.
- This study focuses on infants born at <28 weeks gestation and <1,000g.
Purpose of the Study:
- To evaluate the incidence, risk factors, biochemical markers, and outcomes of MBD in a cohort of extremely preterm infants.
- To assess the utility of parathyroid hormone (PTH) levels in diagnosing MBD and its correlation with radiographic osteopenia.
- To identify predictors of MBD and its association with adverse outcomes in this vulnerable population.
Main Methods:
- A retrospective cohort study of 487 preterm infants admitted to a tertiary NICU in Riyadh, Saudi Arabia (2017-2024).
- MBD was defined by a PTH level >18 pmol/L at 4 weeks, with Receiver Operating Characteristic (ROC) analysis against radiographic osteopenia.
- Clinical characteristics, nutrient intake, growth, and biochemical markers (ALP, phosphate, calcium, vitamin D, PTH) were analyzed using logistic regression.
Main Results:
- MBD was diagnosed in 41.5% of infants, associated with lower gestational age, birth weight, and increased exposure to postnatal steroids, diuretics, and prolonged TPN.
- Infants with MBD exhibited higher PTH and ALP, and lower vitamin D, calcium, and magnesium levels.
- MBD independently predicted fractures, prolonged hospitalization (>60 days), and growth failure, despite similar calcium/phosphate intake.
Conclusions:
- MBD is prevalent in extremely preterm infants, significantly contributing to growth failure and extended hospitalization.
- A 4-week PTH screening demonstrated good discrimination for radiologic osteopenia, supporting its role in structured bone health care.
- Findings suggest targeting modifiable exposures like prolonged TPN, diuretics, and steroids for MBD prevention and highlight the need for external validation of diagnostic thresholds.
Background:
Metabolic bone disease (MBD) of prematurity is a common disorder in extremely preterm and extremely low-birth-weight (ELBW) infants. However, regional data on this disorder from the Middle East are limited. We evaluated the incidence, risk factors, biochemical markers, and outcomes of MBD in infants born at <28 weeks of gestation and <1,000 g.
Methods:
Our retrospective cohort included 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). The clinical characteristics, nutrient intake, growth, and biochemical markers (ALP, phosphate, calcium, vitamin D, PTH) of the infants were analyzed. Logistic regression identified predictors and associations with adverse outcomes.
Results:
MBD was diagnosed in 202 out of 487 infants (41.5%). Compared with infants without MBD, those with MBD had lower GA and birth weight (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 values were higher, while vitamin D, calcium, and magnesium concentrations 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 of >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), while 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 suggested by many reports, plausibly reflecting a structured bone health program (routine biochemical screening, optimized mineral delivery, and minimal handling). Findings support the incorporation of PTH alongside ALP for earlier detection and point to modifiable exposures (prolonged TPN, diuretics, and steroids) as targets for prevention. Prospective multicenter validation with standardized thresholds and imaging strategies is warranted.
Conclusion:
MBD is common in extremely preterm infants and is associated with growth failure and prolonged hospitalization. A 4-week PTH screen showed good discrimination for radiologic osteopenia (AUC 0.78), supporting its role within structured bone health care. As our findings are based on a biochemical definition, diagnostic thresholds require external validation.
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