594 - Association Between Early Postnatal Phosphorus, Magnesium, and Calcium Levels and Neurodevelopmental Outcomes in Extremely Preterm Infants

Publication Number: 3575.594

Alyssa N. Miller, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Erin Kim, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Bich Na Choi, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Claudia Pedroza, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Matthew Rysavy, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Covi Anne Tibe, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Mar Romero-Lopez, UT Health. Houston, Houston, TX, United States

Background: Despite advances in neonatal care, infants born before 27 weeks remain highly vulnerable to neurodevelopmental impairments. Early mineral balance, particularly of phosphorus, magnesium, and calcium, plays a crucial role in brain development. Phosphorus supports energy metabolism and myelination; calcium regulates neuronal signaling and synapse formation; and magnesium stabilizes neuronal function and reduces inflammation. Imbalances can compromise growth and neurodevelopment, yet supplementation practices vary. Optimizing early nutrition may improve outcomes in this high-risk population.

Objective: To examine the association between serum phosphorus, magnesium, and calcium levels during the first 28 days after birth and neurodevelopment at 2 years corrected age in infants born before 27 weeks.

Design/Methods: The study included 179 infants born at < 27 weeks at a major academic center (2020-2022) who survived >24 h. Infants with major congenital anomalies, congenital infections, or who survived to discharge but had missing 2-year exams were excluded (Figure 1). Primary exposures were the mean of serum mineral levels during the first 28 days. Outcomes included neurodevelopmental impairment (NDI; Bayley-III/IV cognitive or motor score < 85, GMFCS ≥II, bilateral blindness, or non-functional hearing) and mortality. A composite of NDI or death was also examined. A multiple linear regression model adjusted for maternal age, antenatal steroids, infant sex, birth weight, and illness severity.

Results: Among 179 infants (mean±SD gestational age 24.5±1.2 wk, birth weight 747±189 g, 50% female), the mean serum phosphorus, magnesium, and calcium over 28 days were 4.65±1.21, 2.61±0.44, and 9.26±1.15, respectively. We observed non-statistically significant but clinically important differences in 2-year developmental outcomes when comparing the first and third tertiles of mineral levels for phosphorus, magnesium, and calcium, as well as Bayley scale scores (Figure 2). Infants with NDI or death, while not statistically significant, exhibited slightly lower mean phosphorus levels at weeks 2 (4.69 ± 1.20 vs. 4.77 ± 1.12) and 3 (4.68 ± 1.21 vs. 4.77 ± 1.05), and statistically significantly lower calcium levels at week 4 (9.54 ± 0.73 vs. 9.69 ± 0.58; p= 0.003) (Figure 3).

Conclusion(s): The patterns we observed suggest that higher early phosphorus and calcium levels may support neurodevelopment. These findings highlight the need for larger, prospective studies to determine whether optimizing mineral management in the early neonatal period could improve long-term outcomes.

Figure 1: Flow diagram showing infant selection and exclusions


Figure 2: BAYLEY's Scaled Score Trends Across Mineral Level Terciles with Mineral Values
Trend lines illustrate non-significant increases in cognitive, language, and motor scores
with higher phosphorus and calcium tertiles, while magnesium tertiles showed no
upward trends.

Figure 3: Weekly Electrolyte Levels: NDI/Death vs No NDI/Death
Overall, higher calcium levels showed a non-significant trend toward lower NDI/Death risk, with week 4 calcium significantly associated with reduced risk. Phosphorus at weeks 2-3 also showed non-significant trends towards lower risk, while magnesium showed no protective trends.