Antenatal Magnesium Sulfate and adverse gastrointestinal outcomes in Preterm infants-a systematic review and meta-analysis

Abstract

Introduction: To evaluate the effect of antenatal magnesium sulfate (MgSO₄) on mortality and morbidity outcomes related to the gastrointestinal system (GI) in preterm infants.

Methods: Data sources: A systematic literature search was conducted in November 2022. PubMed, CINAHL Plus with Full Text (EBSCOhost), Embase (Elsevier), and CENTRAL (Ovid) were searched. There were 6695 references. After deduplication, 4332 remained. Ninety-nine full-text articles were assessed and forty four articles were included in the final analysis.

Study eligibility criteria: Randomized or quasi-randomized clinical trials and observational studies that evaluated at least one of the pre-specified outcomes were included. Preterm infants whose mothers were given antenatal MgSO₄ were included and whose mothers did not receive antenatal MgSO₄ were the comparators. The main outcomes and measures were: Necrotizing enterocolitis (NEC) (stage ≥ 2), surgical NEC, spontaneous intestinal perforation (SIP), feeding intolerance, time to reach full feeds, and GI-associated mortality.

Study appraisal and synthesis methods: A random-effects model meta-analysis was performed to yield pooled OR and its 95% CI for each outcome due to expected heterogeneity in the studies. The analysis for each predefined outcome was performed separately for adjusted and unadjusted comparisons. All included studies were assessed for methodological quality. The risk of bias was assessed using elements of the Cochrane Collaboration's tool 2.0 and the Newcastle-Ottawa Scale for randomized controlled trials (RCTs) and non-randomized studies (NRS), respectively. The study findings were reported as per PRISMA guidelines.

Results: A total of thirty-eight NRS and six RCTs involving 51,466 preterm infants were included in the final analysis. There were no increased odds of stage ≥2 NEC, (NRS : n = 45,524, OR: 0.95; 95% CI: 0.84-1.08, I²- 5% & RCT's: n = 5205 OR: 1.00; 95% CI: 0.89-1.12, I²- 0%), SIP (n = 34,186, OR: 1.22, 95% CI: 0.94-1.58, I²-30%), feeding intolerance (n = 414, OR: 1.06, 95% CI: 0.64-1.76, I²-12%) in infants exposed to antenatal MgSO₄. On the contrary, the incidence of surgical NEC was significantly lower in MgSO₄ exposure infants (n = 29,506 OR:0.74; 95% CI: 0.62-0.90, ARR: 0.47%). Studies assessing the effect on GI-related mortality were limited to make any conceivable conclusion. The certainty of evidence (CoE) for all outcomes was adjudged as 'very low' as per GRADE.

Conclusion: Antenatal magnesium sulfate did not increase the incidence of gastrointestinal-related morbidities or mortality in preterm infants. With the current evidence concerns, regarding the adverse effects of MgSO₄ administration leading to NEC/SIP or GI-related mortality in preterm infants should not be a hurdle in its routine use in antenatal mothers.