Antenatal exposure to magnesium sulfate and the incidence of patent ductus arteriosus in extremely low birth weight infants

Abstract

Objective: Magnesium sulfate (MgSO 4 ) is the most commonly used tocolytic agent in the US and is also employed as a prophylactic agent against seizures in pre-eclamptic women. MgSO 4 crosses the placenta and its concentration in the newborn usually exceeds that of maternal levels. The purpose of this study was to explore the relationship between antenatal exposure to MgSO 4 and the incidence of patent ductus arteriosus (PDA) in extremely low birth weight infants.Study design: A total of 954 neonates with birth weights between 500 and 1000 g, born at the University of Miami/Jackson Memorial Hospital between January 1995 and December 2004 and surviving for more than 3 days, were followed until death or discharge from the hospital. The incidence of PDA in infants exposed to MgSO 4 was compared with those not exposed and comparisons were also made between infants exposed to different maternal doses of MgSO 4 .Results: The incidence of PDA was significantly higher in the group of infants exposed to MgSO 4 compared with the unexposed control group (67 vs. 60%, P<0.018). When stratified by gestational age the differences were significant only in the group of infants with a gestational age of X26 weeks (58 vs. 49%, P<0.039). Logistic regression analysis to adjust for co-variables indicated an increased risk of PDA with higher doses of MgSO 4 (odds ratio 1.33 confidence interval (CI) 1.12 to 1.58, per 50 g of MgSO 4 ). Conclusion:Antenatal exposure to MgSO 4 is associated with a higher risk of PDA in extremely low birth weight infants and this effect is more significant and dose-related in more mature infants.

Antenatal magnesium sulfate and the postnatal response of the ductus arteriosus to indomethacin in extremely preterm neonates

“…Substantial discrepancy exists with regard to the incidence of an sPDA among MgSO 4 -exposed and control infants between the results noted by del Moral et al 11 (67 vs 60%, respectively) and our own results (46 vs 24%, respectively). Indomethacin prophylaxis may have contributed the low incidence of an sPDA in our study.…”

“…del Moral et al 11 reported an increased risk of an sPDA with relatively high doses (X50 g) of antenatal MgSO 4 in infants aged X26 gestational weeks. These authors speculated that the effect of MgSO 4 exposure on risk of an sPDA development in more mature infants was related to the total amount of MgSO 4 provided to the mother.…”

Indomethacin Dosing and Constriction of the Ductus Arteriosus During Open Fetal Surgery for Myelomeningocele Repair

“…As previously demonstrated in a 2009 animal study, hypermagnesemia induced by transplacental magnesium sulfate attenuated the fetal ductus-constricting effects of indomethacin and delayed postnatal ductal closure in rats [5]. This phenomenon has also been reported in extremely preterm neonates in which antenatal magnesium sulfate treatment has been associated with a greater frequency of DA patency and reduced clinical responsiveness of the DA to indomethacin therapy [6,7].…”

Fetal Reversed Constrictive Effect of Indomethacin and Postnatal Delayed Closure of the Ductus Arteriosus following Administration of Transplacental Magnesium Sulfate in Rats

“…There have been a few reports suggesting a relationship between MgSO 4 and premature PDA [10][11][12] . Since the vessel wall of the DA is rich in smooth muscle, an elevated intracellular Ca 2+ level is associated with DA constriction [25] .…”