643 - Impact of Antenatal Steroids, Magnesium Sulfate, and Normothermia on Neonatal Brain Injury in Preterm Infants: A Single-Center Retrospective Analysis

Publication Number: 2627.643

Hillary C. Lee, Baylor College of Medicine, Arlington, TX, United States; Joseph Hagan, Baylor College of Medicine, Houston, TX, United States; Monika S.. Patil, Baylor College of Medicine, Houston, TX, United States

Background: Intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) remain major causes of neurodevelopmental impairment in preterm infants. While antenatal corticosteroids, magnesium sulfate, and thermoregulation individually reduce brain injury risk, their combined effect remains poorly characterized.

Objective: To evaluate the independent and cumulative effects of antenatal corticosteroids, magnesium sulfate, and normothermia on brain injury and resuscitation intensity in preterm infants and to determine whether their combined use confers a dose-dependent neuroprotective effect.

Design/Methods: This retrospective study included preterm infants < 37 weeks and < 1500 g born at a single center (2012-2022). Infants who died in the delivery room or without head imaging were excluded. Neuroprotective factors were antenatal corticosteroids, magnesium, and normothermia (≥36.5 °C). Each infant was assigned a cumulative neuroprotection factor score (0-3) based on number of interventions. Group differences were assessed using chi-squared and Kruskal-Wallis tests; multivariable regressions adjusted for birth weight and sex. Primary outcomes were any IVH, severe IVH (grade 3-4), and composite brain injury (IVH or PVL); secondary outcomes were 5-minute Apgar and resuscitation scores. Resuscitation scores were calculated by assigning 1 point for each intervention (oxygen, continuous positive airway pressure, positive pressure ventilation, alternate airway, chest compressions, epinephrine), with higher scores indicating greater delivery room support.

Results: Baseline characteristics of 1,641 included infants are shown in Table 1. After adjustment, each additional neuroprotective factor was linked with 31% lower odds of any IVH, 38% lower odds of severe IVH, and 31% lower odds of composite brain injury (all p< 0.001). Higher dose exposure also correlated with higher 5-minute Apgar scores (Figure 1). Raw resuscitation scores declined with greater neuroprotection despite a slight adjusted rise, suggesting birth weight confounding (Table 2). Normothermia conferred the greatest independent protective effect (aOR 0.52 for any IVH, 0.49 for severe IVH, 0.54 for composite brain injury; all p≤0.005), higher 5-minute Apgar, and lower resuscitation scores.

Conclusion(s): In this large, single-center preterm cohort, increasing exposure to neuroprotective factors was linked with lower odds of brain injury and improved postnatal outcomes. Normothermia showed the strongest and most modifiable effect, supporting neonatal-led thermoregulation and bundled neuroprotection strategies to reduce brain injury in preterm infants.

Table 1. Maternal and infant characteristics by exposure to antenatal corticosteroids, magnesium sulfate, and no hypothermia (n = 1641).
Groups represent all eight mutually exclusive combinations of neuroprotective interventions. Bolded text indicates infants who received the respective intervention. p-values derived from χ² tests for categorical and Kruskal-Wallis tests for continuous variables.

Figure 1. Incidence of IVH and mean 5-minute Apgar score by number of neuroprotective interventions received (combination of antenatal steroids, magnesium sulfate, and normothermia).
The total height of each gray bar represents the overall incidence of IVH (grade 1-4), while the dark gray segment indicates the subset with severe IVH (grade 3-4). The solid blue line depicts the mean 5-minute Apgar score for each group, with sample sizes (n) shown above the bars. A stepwise reduction in both any and severe IVH was accompanied by a parallel rise in Apgar scores, demonstrating cumulative dose-dependent neuroprotective benefit. Spearman's correlation showed a weak but significant inverse association between neuroprotection dose and IVH grade (ρ=-0.11, p<0.001) and a positive association with Apgar score (ρ=0.07, p=0.004).

Table 2. Rates of any IVH, severe IVH, composite brain injury, and mean 5-minute Apgar and resuscitation scores by total neuroprotection factor dose (0-3).
Factor dose reflects cumulative exposure to antenatal corticosteroids, magnesium sulfate, and normothermia ≥36.5 °C. Percentages and means show unadjusted trends; adjusted odds ratios (aOR) and slopes (β) represent per-unit associations controlling for birth weight and sex. p-values indicate linear dose-response significance from multivariable regression models. Outcomes are shown by total factor exposure; individual combinations yielded consistent results (data not shown).