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Markers of Metabolic Bone Disease in Extremely Preterm and Very Low Birth Weight Infants: A Four-Part Cohort Study
Ilana Levene1, Mar Moreno2, Brian Shine3
1Newborn Care, John Radcliffe Hospital, Oxford University NHS Foundation Trust, Oxford, United Kingdom.
Insights
Routine breastmilk fortification and parathyroid hormone (PTH)-targeted supplementation did not improve markers of metabolic bone disease of prematurity (MBDP). Low 25-hydroxyvitamin D levels were associated with higher PTH and ALP, indicating potential underlying deficiencies.
Area of Science:
- Neonatal care
- Pediatric endocrinology
- Nutritional science
Background:
- Metabolic bone disease of prematurity (MBDP) is a significant concern in extremely preterm infants.
- Current prevention strategies include breastmilk fortification and mineral supplementation.
- The effectiveness of different management approaches requires ongoing evaluation.
Purpose of the Study:
- To analyze the association of MBDP markers with various clinical prevention and management strategies.
- To evaluate the impact of routine breastmilk fortification and parathyroid hormone (PTH)-targeted supplementation on MBDP.
- To identify factors associated with elevated MBDP markers.
Main Methods:
- A four-part cohort study was conducted in a tertiary neonatal unit from 2015 to 2023.
- Infants born under 28 weeks' postmenstrual age or 1.5 kg birthweight were included.
- Cohorts received different interventions: unfortified/fortified breastmilk, universal/targeted phosphate/calcium supplementation, and varied PTH monitoring thresholds.
Main Results:
- No significant improvement in MBDP markers (ALP, fractures, radiographic osteopenia) was observed with routine fortification or PTH-targeted supplementation.
- Elevated alkaline phosphatase (ALP) concentrations were noted in earlier cohorts but stabilized in later ones.
- Lower 25-hydroxyvitamin D, lower birthweight, and higher birth gestation were independently associated with higher ALP; lower 25-hydroxyvitamin D, lower ionized calcium, and lower birthweight were associated with higher PTH.
Conclusions:
- Routine breastmilk fortification and PTH-targeted mineral supplementation did not enhance MBDP markers in this cohort.
- High prevalence of 25-hydroxyvitamin D deficiency may have confounded the results, as it correlated with higher PTH and ALP.
- Further research is needed to optimize MBDP prevention in vulnerable preterm populations, addressing vitamin D status.
Aim:
Analyse the association of markers of metabolic bone disease of prematurity (MBDP) with different clinical approaches to MBDP prevention and management.
Methods:
Four-part cohort study in a tertiary neonatal unit between 2015 and 2023. Eligible infants were born under 28 weeks' postmenstrual age or under 1.5 kg birthweight. Four 1-year periods were included. Baseline cohort received routinely unfortified breastmilk and universal phosphate supplementation. Second cohort received routine breastmilk fortification and universal phosphate supplementation. Third cohort received routine breastmilk fortification and parathyroid hormone (PTH) monitoring with targeted calcium/phosphate supplementation. In the fourth cohort, the PTH threshold for supplementation was increased.
Results:
About 329 infants were included. The highest ALP concentration increased between cohort 1 and 2 (median 466 IU/L; IQR 332-581, median 529 IU/L; IQR 439-809) and remained stable in cohort 3 and 4 (median 570 IU/L; IQR 412-850, median 665 IU/L; IQR 480-868). There was no change in the incidence of osteopenic bone fractures (1/72, 0/84, 0/85, 1/88) or osteopenia on clinical radiographs (4/72, 4/84, 4/85, 7/88). Multivariable analysis identified lower 25-hydroxyvitamin D, lower birthweight and higher birth gestation as the variables independently associated with higher ALP concentration. Multivariable analysis identified lower 25-hydroxyvitamin D, lower ionised calcium, lower birthweight and maternal ethnic minority background as the variables independently associated with higher PTH concentration.
Conclusions:
There was no improvement in markers of MBDP with routine fortification of breastmilk or the use of PTH-targeted mineral supplementation. This may be due to the high level of 25-hydroxyvitamin D deficiency in this cohort, as lower 25-hydroxyvitamin D was associated with higher PTH and ALP.
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