Antenatal magnesium sulfate for both tocolysis and fetal neuroprotection in premature rupture of the membranes before 32 weeks’ gestation

Abstract

Objective: We aimed to assess the impact of antenatal MgSO₄ therapy given to women with PPROM before 32 weeks’ gestation on latency, maternal outcomes, perinatal outcomes, and neurodevelopmental outcomes.

Methods: We undertook a retrospective cohort observational study of 184 singleton pregnancies complicated by PPROM at 23°–31⁶ weeks who were hospitalized and received magnesium therapy for tocolysis (MgSO₄ group) or did not receive tocolytic therapy (no MgSO₄ group) between 2005 and 2013. Furthermore, patients were subdivided into two groups based on the gestational age at the onset of PPROM (23°–27⁶ weeks’ gestation and 28°–31⁶ weeks’ gestation).

Results: We included 184 women, of whom 143 received magnesium therapy and 41 did not. The latency period was significantly longer in the MgSO₄ group compared with no MgSO₄ group (7.9 ± 9.0 versus 4.0 ± 6.0 days, p = .0017). Antenatal magnesium therapy was significantly associated with decreased stillbirth (1.4% versus 14.6%, p = .0012) and perinatal mortality (7% versus 19.5%, p = .0375) without significant increase in the risk of neonatal morbidities and chorioamnionitis. However, neonates who were exposed to antenatal MgSO₄ were associated with higher Mg levels (3.63 ± 1.05 mg/dl versus 2.13 ± 0.48 mg/dl, p < .0001) and phosphate levels (6.90 ± 1.36 mg/d versus 6.40 ± 1.01 mg/dl, p = .0459) than those who were not exposed. Neonates who were exposed to MgSO₄ showed significantly reduced risks of IVH (20.4% versus 58.3%; RR, 0.35; 95%CI, 0.17–0.71) and PVL (27.8% versus 58.3%; RR, 0.48; 95%CI, 0.25–0.91) in the subgroup of 23°–27⁶ weeks’ gestation. And the incidence of developmental delay in the subgroup of 23°–27⁶ weeks’ gestation was significantly lower in the MgSO₄ group (6.5% versus 36.4%; RR, 0.18; 95%CI, 0.05–0.69). However, there were no significant differences in the development of IVH, PVL, and developmental delay between the two groups for patients in the subgroup of 28°–31⁶ weeks’ gestation. A similar trend was observed for cerebral palsy, with 22.2% of unexposed children affected compared with only 7.0% of exposed children (RR, 0.31; 95%CI, 0.10–1.00).

Conclusions: Antenatal magnesium therapy in women with PPROM before 32 weeks’ gestation could prolong latency period, allowing for corticosteroid benefit. Moreover, MgSO₄ showed fetal neuroprotective effects for neonatal IVH and PVL, and for developmental delay in infancy while prolonging latency. However, these benefits were primarily limited to the subgroup of 23°–27⁶ weeks’ gestation and prolonged in utero exposure to MgSO₄ was associated with bone mineralization in the neonates.

Keywords:

• Magnesium sulfate
• preterm premature rupture of the membranes
• tocolysis
• neuroprotection

Acknowledgements

No sources of support including sponsorship and sources of material.

Disclosure statement

None of the authors has personal or financial conflict of interests.