Background Low dose antenatal magnesium sulfate (MgSO4) was found to be an effective neuroprotective intervention. However there is evidence from animal and clinical studies that high dose magnesium can have detri-mental effects to the foetal brain. Optimal dose and duration of magnesium treatment are still unknown although PK models have been described. The aim of this study was to explore associations between antenatal magne-sium exposure, neonatal magnesium levels, neonatal ce-rebral and echocardiographic biomarkers.
Methods This is a prospective observation study re-cruiting preterm neonates 24–28+6 weeks’ gestation and postnatal age ≤72 hours. Echocardiography (PDA severity score), cranial ultrasonography [grade of intraventricular haemorrhage (IVH)], amplitude integrated electroen-cephalogram (aEEG) (Burdjalov score a composite score for the measurement of cerebral maturity) and near in-frared spectroscopy [cerebral tissue oxygenation index (cTOI)] were measured during the transitional period and associated with neonatal magnesium levels.
Results 51 infants were included with median gestation-al age of 26.6 weeks [Interquartile range (IQR) 25.7–28] and median birth weight (BW) of 900 grams (IQR 760–1,080). Thirty three mothers (65%) received antenatal magne-sium sulphate for neuroprotection (included seven who had preeclampsia) and eighteen (35%) did not receive. The median duration of magnesium sulphate infusion was 7.5 hours (IQR 3–12). Neonates exposed to antenatal magnesium had significant higher magnesium levels in the first two days after birth (p<0.001). Duration of an-tenatal magnesium exposure was also significantly cor-related with neonatal magnesium levels in the first three days of life (Day 1, p<0.001, R2=0.774). There was a signifi-cant negative correlation between maternal weight and body mass index (BMI) and neonatal magnesium levels on second and third day of life (Day 2: p=0.005 and 0.013 respectively). Higher gestation and birth weight was also associated with higher neonatal Mg levels on third day of life (p=0.008 and 0.012 respectively). Mg did not have any significant effect on echocardiographic biomarkers. Neonatal Mg levels on second and third after birth were correlated with cerebral tissue oxygenation and Burdjalov score. Infants with a higher serum Mg on Day 3 were more likely to have normal cranial scan result (p=0.017). A model was created using MgSO4 administration, BW, maternal BMI as the main background demographics parameters which may have significant effect on the cerebral and cardiovascular biomarkers and severity of cerebral injury.
Conclusion As expected, antenatal MgSO4 had signif-icant effects on neonatal magnesium levels. Maternal BMI and neonatal BW have significant impact on neona-tal Mg levels and possibly on clinical outcomes. Further dose-finding studies should be based on multicompart-mental population PK studies that include maternal and neonatal PD measures.
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