662 - Prenatal Magnesium Sulfate Exposure is Not Associated with Different Neurodevelopmental Outcomes by Sex in Extremely Preterm Infants

Publication Number: 662.6319

Kate F. DiNucci, University of Washington School of Medicine, Seattle, WA, United States; Olivia C. Brandon, University of Washington: Magnuson Health Sciences Center – RR 544A, Seattle, WA, United States; Kylie Corry, University of Washington School of Medicine, Seattle, WA, United States; Patrick Heagerty, University of Washington, Seattle, WA, United States; Dennis E. Mayock, UWMC, Lake Forest Park, WA, United States; Sandra E. Juul, University of Washington, Seattle, WA, United States; Thomas R. Wood, University of Washington School of Medicine, Seattle, WA, United States

Background: Magnesium sulfate (MagSulf) has historically been used in obstetrics as a tocolytic and to prevent eclamptic seizures. More recently, MagSulf has been investigated as a potential neonatal neuroprotectant for infants born preterm. However, randomized controlled trials of prenatal MagSulf have shown mixed results, with single center studies also suggesting differential effects by sex.

Objective: We sought to evaluate sex-dependent associations between prenatal MagSulf exposure and standardized neurodevelopmental outcomes in a large, multi-center cohort of extremely preterm neonates (24-0/7 to 27-6/7 weeks’ gestation) from the Preterm Erythropoietin NeUroproTection (PENUT) Trial.

Design/Methods: We utilized the PENUT dataset to evaluate the outcomes of infants who received antenatal MagSulf, stratified by sex. Neurodevelopmental outcomes were assessed at 2 years using the Bayley Scales of Infant and Toddler Development Index, 3rd edition (BSID-III). All infants who survived and received assessment of at least one BSID-III subscale assessment and had recorded MagSulf exposure were included (n=666) (Table 1). To account for confounding by indication, we performed both matching and inverse probability weighting using 17 maternal predictors of MagSulf exposure. Absolute effects and interactions by sex of MagSulf on BSID-III scores were determined using generalized estimating equations (GEE) (Table 2).

Results: Prior to weighting/matching, the majority of maternal risk factors were imbalanced between MagSulf exposed (n=562) and non-exposed (n=104; standardized mean difference >0.1, Figure 1A). In unadjusted analysis, no significant difference in BSID-III subscales between the MagSulf exposed and non-exposed infants was seen either overall or by sex (Table 1, Figure 1B). Similarly, after adjustment (matching or inverse probability weighting), no sex effect of antenatal MagSulf exposure on neurodevelopmental outcomes was seen (Table 1, Figure 1C).

Conclusion(s): In this large multi-center cohort of extremely preterm infants there was no association between MagSulf exposure and neurodevelopmental outcome in survivors, and no sexually-dimorphic response to MagSulf. This study reaffirms the safety of antenatal MagSulf administration but does not support the use of MagSulf for neuroprotection.

Table 1. Cohort characteristics.
Infant and maternal characteristics, by MagSulf exposure and statistical analysis method.

Table 2. Effect estimates of magnesium sulfate exposure by sex.
Effects and confidence intervals estimated with GEE, clustering on mother using an independent correlation structure with robust standard errors.

Figure 1
Figure 1 Mag Sulf .jpegFigure 1 A. Standardized Mean Difference of MagSulf exposure by method. Difference between exposed and unexposed MgSO4 groups across maternal/birth covariates when entire sample weighted using Inverse Probability Weighting (Weighted) vs not weighted (Unadjusted) vs restricted to matched sample (Matched). Maternal characteristics were imbalanced in unadjusted group comparison, matched and weighted analysis adjusted for balanced maternal characteristics in comparison.
B. MagSulf exposure and BSID outcomes by sex – unadjusted. Infant outcomes by sex and Magnesium Sulfate exposure (n=660). Motor score missing n=10; Language score missing n=13. No significant difference between outcomes by Magsulf exposure or sex.
C. MagSulf exposure and BSID outcomes by sex – adjusted. Infant outcomes by magnesium sulfate exposure status and baby sex in sample matched on all maternal/birth covariates except for chorio (n=312). No significant difference between outcomes by Magsulf exposure or sex.