Breast milk intake, intact parathyroid hormone, and %tubular phosphate reabsorption as predictors of bone mineral density at term-equivalent age in very preterm and/or low-birth-weight infants: A prospective cohort study.

BACKGROUND: Predicting and preventing metabolic bone disease (MBD) in preterm infants remains challenging. AIMS: To evaluate the associations of bone mineral density (BMD) with fortified breast milk intake, and biochemical markers, including intact parathyroid hormone (iPTH), and %tubular phosphate reabsorption (%TRP). STUDY DESIGN: A prospective observational study conducted at a single tertiary center in Japan. SUBJECTS: Infants born at ≤31 weeks of gestation and/or birth weight ≤ 1500 g from August 2018 to August 2020. OUTCOME MEASURES: Cord blood iPTH and 25-hydroxyvitamin D, weekly serum iPTH, alkaline phosphatase (ALP), and %TRP were measured until term-equivalent age (TEA). BMD at TEA was assessed using dual-energy X-ray absorptiometry. Associations between clinical and biochemical variables and BMD were analyzed. RESULTS: Of 137 infants screened, 105 were included in the analysis. Higher breast milk intake was positively correlated with BMD, whereas elevated iPTH levels and lower %TRP at 3-8 weeks were negatively correlated with BMD. In multivariable regression analysis, birth weight and breast milk intake were positively correlated with BMD, whereas iPTH levels at 4 weeks were negatively associated. A linear mixed-effects model confirmed this longitudinal association. Gestational age, ALP, and 25-hydroxyvitamin D levels were not associated with BMD. CONCLUSION: Lower breast milk intake and elevated iPTH levels are indicators of reduced BMD at TEA in very preterm and very-low-birth-weight infants. %TRP may serve as a practical alternative marker, when iPTH measurements are unavailable. Early monitoring of iPTH and/or %TRP, combined with optimized fortified breast milk intake, may support bone health in this high-risk population.