Professor of Pediatrics Children's Hospital of Michigan Pittsford, New York, United States
Background: Premature infants are at increased risk for metabolic bone disease (MBD) characterized by decreased bone mineral density (BMD). In addition to prematurity, in-utero and post-natal conditions play role in the pathogenesis of MBD. In-utero vitamin D status may influence BMD; however, its association with BMD has not been well studied in premature infants. Objective: To determine if in-utero vitamin D status is associated with BMD at term age in 24-32 weeks gestational age (GA) infants. We hypothesized that infants with in-utero vitamin D deficiency (cord blood 25 hydroxy-vitamin D [25-OH VD] < 20 ng/mL) will have lower BMD compared to infants with normal in-utero vitamin D status (25-OH VD ≥ 20 ng/mL). Design/Methods: A prospective cohort study was performed to compare BMD at term age between premature infants with and without in-utero vitamin D deficiency. Our inclusion criteria were in-born 24-32 weeks GA infants admitted to the Neonatal Intensive Care Unit and who had cord blood collected. Infants with chromosomal disorders, congenital malformations, skeletal disorders, or moribund condition were excluded. In addition, infants for whom Dual-energy X-ray absorptiometry (DXA) scans could not be performed at term age were excluded. Cord blood was used to measure 25-OH VD levels using the Liquid Chromatography-Tandem Mass Spectrometry method. BMD (g/cm2) was evaluated using DXA at term age (37-40 weeks post-menstrual age) by a certified examiner unaware of vitamin D status. Net (Lumbar spine plus left femur) BMD was used as an outcome measure. Results: 90 infants who met study criteria were enrolled after obtaining consent. Of these, 7 infants (3 transferred, 2 died, and 2 on respiratory support) could not have DXA at term age. The mean (Median) GA and mean (Median) birth weight of 83 infants were 27.8 (27.5) weeks and 1095 (980) g, respectively. The mean (median) net BMD of 83 infants was 0.10 (0.099) g/cm2. Of 83 infants studied, 36 infants had in-utero vitamin D deficiency. There was no significant difference in clinical characteristics except for race between infants with in-utero vitamin D deficiency and infants without in-utero vitamin D deficiency (Table). Race, birth weight, and sex were considered potential confounders (p ≤ 0.1) and included in the full regression model. On regression analyses, in-utero vitamin D deficiency was not associated with lower BMD at term age (coefficient -0.0004, 95% CI: -0.007 to 0.007, p = 0.9) after controlling for confounders.
Conclusion(s): In-utero vitamin D status may not be associated with MBD of prematurity as evaluated by BMD at term age in 24-32 weeks GA infants.