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Interventions for metabolic bone disease of prematurity: A systematic review and meta-analysis
Yazan Jumah Alalwani1, Mujood Ali Alatta1, Khawlah Abdullah Almana2
1College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Insights
Nutritional prophylaxis significantly reduces metabolic bone disease of prematurity (MBDP) incidence by 54%. Mechanical interventions improve bone mineralization, suggesting combined strategies may offer optimal prevention for very low birth weight infants.
Area of Science:
- Neonatology
- Pediatric Bone Health
- Nutritional Science
Background:
- Metabolic bone disease of prematurity (MBDP) affects up to 30% of very low birth weight infants.
- Evidence for prevention and treatment strategies for MBDP is limited.
- This study evaluates interventions for MBDP in preterm infants.
Purpose of the Study:
- To evaluate the efficacy and safety of nutritional, mechanical, and pharmacological interventions for MBDP.
- To assess the impact of these interventions on MBDP incidence, bone mineral density, and safety profiles.
- To provide evidence-based recommendations for MBDP prevention and treatment.
Main Methods:
- Systematic review and meta-analysis following PRISMA 2020 guidelines.
- Searched five databases for studies on MBDP interventions in preterm infants (<37 weeks or <1500g).
- Included random-effects meta-analyses, trial sequential analysis (TSA), and GRADE assessments.
Main Results:
- Eighteen studies (1577 infants) were included.
- Nutritional prophylaxis reduced MBDP incidence by 54% (RR=0.46), with early calcium/phosphorus supplementation showing 74-84% risk reduction.
- Mechanical interventions improved bone mineral content (28%), ultrasound speed-of-sound (MD=75.3 m/s), and weight gain (MD=5.11 g/kg/day).
Conclusions:
- Nutritional prophylaxis conclusively reduces MBDP incidence.
- Mechanical interventions effectively improve bone mineralization in preterm infants.
- Integrating nutritional and mechanical strategies may optimize MBDP prevention, with further research needed on orthopedic management.
Introduction:
Metabolic bone disease of prematurity (MBDP) affects up to 30 % of very low birth weight infants; however, evidence regarding prevention and treatment strategies remains limited. We aimed to evaluate the efficacy and safety of nutritional, mechanical, and pharmacological interventions for MBDP.
Methods:
Following PRISMA 2020 guidelines, we searched five databases from inception to May 5, 2025, for studies evaluating interventions for MBDP in preterm infants (<37 weeks or <1500g). Primary outcomes included MBDP incidence, bone mineral density, and safety profiles. Random-effects meta-analyses, trial sequential analysis (TSA), and GRADE assessments were conducted.
Results:
Eighteen studies (1577 infants) from ten countries met inclusion criteria. Nutritional prophylaxis significantly reduced MBDP incidence by 54 % (risk ratio [RR] = 0.46, 95 % confidence interval [CI] 0.30-0.68, P-value<0.001), with early calcium/phosphorus supplementation achieving 74-84 % risk reduction. TSA confirmed conclusive evidence, with cumulative Z-score (-5.99) crossing the O'Brien-Fleming boundary at 270.9 % of required information size. Number needed to treat was five at 40 % baseline risk. Mechanical interventions improved bone mineral content by 28 % (P-value<0.01), quantitative ultrasound speed-of-sound (mean difference [MD] = 75.3 m/s, 95 % CI 45.2-105.4), and weight gain (MD = 5.11 g/kg/day, 95 % CI 3.95-6.27). Both interventions demonstrated favorable safety profiles, with mechanical protocols reporting no adverse events.
Conclusions:
Nutritional prophylaxis conclusively reduces MBDP incidence, while mechanical interventions effectively improve bone mineralization. Although no studies directly evaluated combined approaches, the complementary mechanisms of nutritional and mechanical interventions suggest that optimal prevention may involve integrating both strategies. Critical gaps persist in orthopedic management, necessitating future research on fracture protocols and surgical interventions.
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