Magnesium Sulfate as a Core Tocolytic in Open Fetal Myelomeningocele Repair: Maternal and Fetal Outcomes—A Narrative Review of Evidence from the MOMS Trial Era to 2024

Background/Objectives: Open fetal repair of myelomeningocele (MMC) requires profound and sustained uterine relaxation to permit hysterotomy and to prevent preterm labor after closure. Magnesium sulfate (MgSO4) has become the cornerstone postoperative tocolytic across North American fetal therapy centers, combined with volatile anesthetic-induced intraoperative tocolysis, indomethacin, and/or nifedipine. We synthesize the evidence on the mechanism, dosing, maternal safety, fetal/neonatal effects, and comparative performance of MgSO4 as the core tocolytic in open fetal MMC repair. Methods: We conducted a narrative review of primary studies, consensus statements, and society guidelines published between 2010 and 2024, identified through PubMed, Scopus, ScienceDirect, society repositories (ACOG, SMFM, SPA, NAFTNet, and SOAP), and indexed proceedings of the International Fetal Medicine and Surgery Society. The search strategy, eligibility criteria, and selection process are reported and each contributing source was assigned a level of evidence adapted from the Oxford Centre for Evidence-Based Medicine hierarchy, so that randomized and meta-analytic data were distinguished throughout from case series, pharmacokinetic work, mechanistic studies, and consensus documents. Results: Across the MOMS cohort and post-MOMS series, the standard regimen is a 4–6 g intravenous loading dose followed by 1–3 g/h infusion for 24–48 h, layered on perioperative indomethacin and intraoperative volatile tocolysis. MgSO4 provides effective myometrial quiescence and is associated with pulmonary edema in ~5–6% of mothers, near-universal lethargy and electrolyte disturbance, occasional high-grade atrioventricular block, transient neonatal hypotonia, and reduced fetal heart-rate variability. The neuroprotective effect of magnesium (cerebral palsy RR: 0.68; 95% CI: 0.54–0.87) is Level 1 but indirect: it was demonstrated in trials in which magnesium was given when preterm birth was planned or expected within approximately 24 h, and it cannot be assumed to persist when the 24–48 h perioperative course precedes delivery by several weeks, as it does after repair at 19–26 weeks with delivery at a mean of 34 weeks. In this population, neuroprotection, therefore, depends on a repeat course administered when preterm birth becomes imminent rather than on the operative infusion itself. Atosiban achieves comparable short-term tocolysis with minimal maternal adverse effects and has no intrinsic neuroprotective action; because neuroprotection in this setting requires magnesium re-administration close to delivery in any case, this difference is a smaller discriminator between the two agents than previously assumed. Conclusions: MgSO4 remains the de facto standard postoperative tocolytic for open fetal MMC repair based on the strength of MOMS-era protocols and accumulated safety experience, supported by the availability of a neuroprotective regimen using the same agent should preterm birth threaten. This rationale rests predominantly on Level 4–5 evidence within the fetal surgery population itself. The optimal dose, duration, timing of initiation, and head-to-head performance against atosiban remain unresolved and warrant a multicenter randomized comparison. Because the species that crosses the placenta and mediates both tocolysis and neuroprotection is the free Mg2+ ion, the sulfate anion being a pharmacologically inert counter-ion, fetal exposure is determined by the maternal ionized-magnesium profile rather than by the salt administered. Only parenteral magnesium can reach tocolytic concentrations, and oral organic preparations such as magnesium glycinate cannot substitute for intravenous MgSO4 or reduce pulmonary edema, which is driven by magnesium exposure and fluid balance and is mitigated by concentrated infusions, strict fluid restriction, the shortest effective duration, and avoidance of co-tocolytics.