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Journal of Perinatology : Official... Sep 2023To evaluate the effect of antenatal magnesium sulfate (MgSO) on mortality and morbidity outcomes related to the gastrointestinal system (GI) in preterm infants. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
To evaluate the effect of antenatal magnesium sulfate (MgSO) 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 MgSO were included and whose mothers did not receive antenatal MgSO 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, I- 5% & RCT's: n = 5205 OR: 1.00; 95% CI: 0.89-1.12, I- 0%), SIP (n = 34,186, OR: 1.22, 95% CI: 0.94-1.58, I-30%), feeding intolerance (n = 414, OR: 1.06, 95% CI: 0.64-1.76, I-12%) in infants exposed to antenatal MgSO. On the contrary, the incidence of surgical NEC was significantly lower in MgSO 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 MgSO administration leading to NEC/SIP or GI-related mortality in preterm infants should not be a hurdle in its routine use in antenatal mothers.
Topics: Infant; Infant, Newborn; Humans; Magnesium Sulfate; Infant, Premature; Enterocolitis, Necrotizing; Infant, Premature, Diseases; Incidence
PubMed: 37391507
DOI: 10.1038/s41372-023-01710-8 -
Current Opinion in Obstetrics &... Apr 2019The aim of this review is to describe the proposed mechanisms of action of magnesium sulfate for fetal neuroprotection, different dosing regimens of the drug that have... (Review)
Review
PURPOSE OF REVIEW
The aim of this review is to describe the proposed mechanisms of action of magnesium sulfate for fetal neuroprotection, different dosing regimens of the drug that have shown benefit, and to review recent pharmacokinetic studies of the drug to better inform clinicians regarding expected benefits and remaining research questions.
RECENT FINDINGS
Retrospective secondary analysis of the beneficial effects of antenatal magnesium sulfate trial database and prospective pharmacokinetic/pharmacodynamic modeling indicate magnesium sulfate administration for duration longer than 18 h, given within 12 h of delivery, and maintaining a maternal serum level of 4.1 mg/dl may maximize the neuroprotective benefits of the drug.
SUMMARY
Magnesium sulfate in some dosage given before very preterm pregnancy delivery is beneficial for fetal neuroprotection. The exact dose, duration, and timing of administration to maximize this benefit may be more precisely studied using pharmacokinetic/pharmacodynamic modeling techniques before conducting larger randomized trials.
Topics: Central Nervous System Diseases; Dose-Response Relationship, Drug; Female; Humans; Infant, Premature, Diseases; Magnesium Sulfate; Maternal-Fetal Exchange; Neuroprotective Agents; Pregnancy; Premature Birth; Prenatal Care; Retrospective Studies; Risk Assessment
PubMed: 30747745
DOI: 10.1097/GCO.0000000000000529 -
NeoReviews May 2020
Topics: Adult; Cardiotocography; Female; Heart Rate, Fetal; Humans; Infant, Newborn; Infant, Newborn, Diseases; Labor, Induced; Magnesium Sulfate; Obstetric Labor Complications; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Tocolytic Agents
PubMed: 32358150
DOI: 10.1542/neo.21-5-e353 -
PLoS Medicine Dec 2019There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing preterm labour and birth (tocolysis) is unproven. We conducted a systematic review and meta-analysis to assess whether antenatal magnesium sulphate is associated with unintended adverse neonatal outcomes.
METHODS AND FINDINGS
CINAHL, Cochrane Library, LILACS, MEDLINE, Embase, TOXLINE, and Web of Science, were searched (inceptions to 3 September 2019). Randomised, quasi-randomised, and non-randomised trials, cohort and case-control studies, and case reports assessing antenatal magnesium sulphate for pre-eclampsia, eclampsia, fetal neuroprotection, or tocolysis, compared with placebo/no treatment or a different magnesium sulphate regimen, were included. The primary outcome was perinatal death. Secondary outcomes included pre-specified and non-pre-specified adverse neonatal outcomes. Two reviewers screened 5,890 articles, extracted data, and assessed risk of bias following Cochrane Handbook and RTI Item Bank guidance. For randomised trials, pooled risk ratios (RRs) or mean differences, with 95% confidence intervals (CIs), were calculated using fixed- or random-effects meta-analysis. Non-randomised data were tabulated and narratively summarised. We included 197 studies (40 randomised trials, 138 non-randomised studies, and 19 case reports), of mixed quality. The 40 trials (randomising 19,265 women and their babies) were conducted from 1987 to 2018 across high- (16 trials) and low/middle-income countries (23 trials) (1 mixed). Indications included pre-eclampsia/eclampsia (24 trials), fetal neuroprotection (7 trials), and tocolysis (9 trials); 18 trials compared magnesium sulphate with placebo/no treatment, and 22 compared different regimens. For perinatal death, no clear difference in randomised trials was observed between magnesium sulphate and placebo/no treatment (RR 1.01; 95% CI 0.92 to 1.10; 8 trials, 13,654 babies), nor between regimens. Eleven of 138 non-randomised studies reported on perinatal death. Only 1 cohort (127 babies; moderate to high risk of bias) observed an increased risk of perinatal death with >48 versus ≤48 grams magnesium sulphate exposure for tocolysis. No clear secondary adverse neonatal outcomes were observed in randomised trials, and a very limited number of possible adverse outcomes warranting further consideration were identified in non-randomised studies. Where non-randomised studies observed possible harms, often no or few confounders were controlled for (moderate to high risk of bias), samples were small (200 babies or fewer), and/or results were from subgroup analyses. Limitations include missing data for important outcomes across most studies, heterogeneity of included studies, and inclusion of published data only.
CONCLUSIONS
Our findings do not support clear associations between antenatal magnesium sulphate for beneficial indications and adverse neonatal outcomes. Further large, high-quality studies (prospective cohorts or individual participant data meta-analyses) assessing specific outcomes, or the impact of regimen, pregnancy, or birth characteristics on these outcomes, would further inform safety recommendations. PROSPERO: CRD42013004451.
Topics: Case-Control Studies; Eclampsia; Female; Humans; Magnesium Sulfate; Obstetric Labor, Premature; Parturition; Pre-Eclampsia; Pregnancy; Premature Birth; Prenatal Care; Prospective Studies
PubMed: 31809499
DOI: 10.1371/journal.pmed.1002988 -
Obstetrical & Gynecological Survey May 2020In cases of anticipated preterm delivery, corticosteroids for fetal lung maturation and magnesium sulfate for fetal neuroprotection may improve neonatal outcomes. (Review)
Review
IMPORTANCE
In cases of anticipated preterm delivery, corticosteroids for fetal lung maturation and magnesium sulfate for fetal neuroprotection may improve neonatal outcomes.
OBJECTIVE
The aim of this study was to summarize and compare published guidelines from 4 leading medical societies on the administration of antenatal corticosteroids and magnesium sulfate.
EVIDENCE ACQUISITION
A descriptive review of major national guidelines on corticosteroids and magnesium sulfate was conducted: National Institute for Health and Care Excellence on "Preterm labour and birth," World Health Organization on "WHO recommendations on interventions to improve preterm birth outcomes," American College of Obstetricians and Gynecologists on "Antenatal corticosteroid therapy for fetal maturation" and "Magnesium sulfate use in obstetrics," and Society of Obstetricians and Gynecologists of Canada on "Antenatal corticosteroid therapy for improving neonatal outcomes" and "Magnesium sulphate for fetal neuroprotection."
RESULTS
A variation in the appropriate timing of administration exists, whereas repeated courses are not routinely recommended for corticosteroids or magnesium sulfate. In addition, the recommendations are the same for singleton and multiple gestations, and no specific recommendation exists according to maternal body mass index. Finally, a variation in guidelines regarding the administration of corticosteroids before cesarean delivery exists.
CONCLUSION
The adoption of an international consensus on corticosteroids and magnesium sulfate may increase their endorsement by health care professionals, leading to more favorable neonatal outcomes after preterm delivery.
Topics: Adrenal Cortex Hormones; Cesarean Section; Drug Administration Schedule; Female; Humans; Magnesium Sulfate; Practice Guidelines as Topic; Pregnancy; Premature Birth; Prenatal Care; Tocolytic Agents
PubMed: 32469415
DOI: 10.1097/OGX.0000000000000778 -
Tropical Medicine & International... Oct 2021Tetanus is a rare life-threatening condition often complicated by repetitive spasms, dysautonomia and neuromuscular respiratory failure contributing to high fatality...
Tetanus is a rare life-threatening condition often complicated by repetitive spasms, dysautonomia and neuromuscular respiratory failure contributing to high fatality rates in its severe form. Benzodiazepines used to treat muscle spasms pose a high risk of respiratory failure requiring mechanical ventilation, which is unaffordable and inaccessible for many. Magnesium sulfate, a cheap and widely available medication in all urban and rural health centres of LMICs for the treatment of eclampsia, can be used to control muscle spasms and dysautonomia. We thus conducted a systematic review of evidence to assess the safety and efficacy of magnesium sulfate in the treatment of tetanus. Any study published before April 15, 2021, discussing the efficacy and/or safety of MgSO4 infusion in the treatment of tetanus was systemically reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Our systematic review included data from 13 studies, three were randomised, double-blind and controlled trials. The remaining ten studies were observational; six prospective and four retrospective studies. Our review showed no mortality benefit associated with the use of magnesium sulfate. However, magnesium sulfate was found to be effective in reducing spasms along with diazepam, leading to better control of dysautonomia, reduced need for mechanical ventilation and shorter hospital stay by 3-7 days. The incidence of magnesium toxicity was very low in the studies included.
Topics: Anticonvulsants; Humans; Magnesium Sulfate; Tetanus
PubMed: 34403179
DOI: 10.1111/tmi.13667 -
Archives of Disease in Childhood. Fetal... Nov 2015The neuro-protective effect of antenatal magnesium sulfate on very preterm infants has been demonstrated in good-quality randomised controlled trials and meta-analyses.... (Review)
Review
The neuro-protective effect of antenatal magnesium sulfate on very preterm infants has been demonstrated in good-quality randomised controlled trials and meta-analyses. Magnesium administered prior to preterm delivery crosses over to the foetal circulation and acts via several pathways to reduce perinatal neuronal damage. Meta-analysis of the trial data indicates that antenatal magnesium sulfate reduces the risk of cerebral palsy by one-third, and results in one fewer case in every 50 women treated. Treatment is associated with discomfort and flushing in some women, but maternal side-effects are mostly transient and manageable. Magnesium sulfate has also been found to be without any serious adverse consequences in newborn infants. Consensus recommendations and guidelines have been developed and implemented internationally, and endorsed by the UK Royal College of Obstetricians and Gynaecologists. However, magnesium sulfate for neuro-protection of very preterm infants has not yet become established widely in UK practice. Paediatricians, neonatologists and advocacy groups for preterm infants and their families could contribute to raising awareness and engage in dissemination activities and implementation initiatives to develop local protocols for adoption of this safe, effective and cost-effective intervention to reduce the burden of cerebral palsy in children born very preterm.
Topics: Cerebral Palsy; Female; Humans; Infant, Newborn; Infant, Premature; Magnesium Sulfate; Neuroprotective Agents; Pregnancy
PubMed: 25896966
DOI: 10.1136/archdischild-2014-307655 -
Seizure Nov 2015Our goal was to perform a systematic review of the literature on the use of intravenous magnesium sulfate (MgSO4) for non-eclamptic status epilepticus (SE) and... (Review)
Review
BACKGROUND
Our goal was to perform a systematic review of the literature on the use of intravenous magnesium sulfate (MgSO4) for non-eclamptic status epilepticus (SE) and refractory status epilepticus (RSE).
METHODS
Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to June 2015), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers.
RESULTS
We identified 19 original articles. A total of 28 patients were described in these articles with 11 being adult, 9 being pediatric, and 8 of unknown age. Seizure reduction/control with IV MgSO4 occurred in 14 of the 28 patients (50.0%), with 2 (7.1%) and 12 (42.9%) displaying partial and complete responses respectively. Seizures recurred upon withdrawal of MgSO4 therapy in 50% of the patients whom had reduction/control of their SE/RSE. Three patients had recorded adverse events related to MgSO4 therapy.
CONCLUSIONS
Oxford level 4, GRADE D evidence exists to suggest a trend towards improved seizure control with the use of intravenous MgSO4 for non-eclamptic RSE. Routine use of IV MgSO4 in non-eclamptic SE/RSE cannot be recommended at this time. Further prospective study of this drug is required in order to determine its efficacy as an anti-epileptic in this setting.
Topics: Administration, Intravenous; Anticonvulsants; Humans; Magnesium Sulfate; Status Epilepticus
PubMed: 26552572
DOI: 10.1016/j.seizure.2015.09.017 -
Pediatrics and Neonatology Mar 2021Antenatal magnesium sulfate is widely used as a tocolytic, for maternal seizures, and for seizure prophylaxis in preeclampsia. Recent studies have suggested that...
BACKGROUND
Antenatal magnesium sulfate is widely used as a tocolytic, for maternal seizures, and for seizure prophylaxis in preeclampsia. Recent studies have suggested that antenatal magnesium sulfate use is associated with favorable neurodevelopmental outcomes in preterm infants. However, there are concerns regarding the effects of antenatal magnesium sulfate on neonates, especially regarding gastrointestinal morbidities. This study aims to explore the effects of antenatal magnesium sulfate on intestinal morbidities requiring surgery in preterm infants.
METHODS
This was a retrospective cohort study of 181 preterm infants who were born at less than 28 weeks of gestational age. Subjects were categorized as infants exposed to antenatal magnesium sulfate and those not exposed to antenatal magnesium sulfate.
RESULTS
Antenatal magnesium sulfate was associated with a decreased risk of surgical conditions of the intestine (OR 0.393, 95% CI 0.170-0.905). The multivariate analysis showed that the duration of antenatal magnesium sulfate use was associated with surgical conditions of the intestine (adjusted OR 0.766, 95% CI 0.589-0.997). In the <26 weeks of gestational age subgroup, the use of antenatal magnesium sulfate was significantly associated with decreased intestinal morbidities requiring surgery (adjusted OR 0.234, 95% CI 0.060-0.922).
CONCLUSION
Antenatal magnesium sulfate use appears to have a protective effect on intestinal morbidities requiring surgery in preterm infants in a duration-dependent manner. Association of antenatal magnesium sulfate use and decreased intestinal morbidities requiring surgery was more distinct in preterm infants <26 weeks of gestational age.
Topics: Cohort Studies; Drug Administration Schedule; Enterocolitis, Necrotizing; Female; Humans; Infant; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Intestinal Perforation; Magnesium Sulfate; Male; Pregnancy; Prenatal Care; Retrospective Studies; Tocolytic Agents
PubMed: 33495105
DOI: 10.1016/j.pedneo.2020.12.009 -
Intensive Care Medicine Nov 2023Studies have suggested benefits from magnesium sulphate in thrombotic thrombocytopenic purpura (TTP). We aimed to measure the effects of magnesium sulphate... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Studies have suggested benefits from magnesium sulphate in thrombotic thrombocytopenic purpura (TTP). We aimed to measure the effects of magnesium sulphate supplementation on TTP recovery.
METHODS
In this multicenter, randomised, double-blind, controlled, superiority study, we enrolled adults with a clinical diagnosis of TTP. Patients were randomly allocated to receive magnesium sulphate (6 g intravenously followed by a continuous infusion of 6 g/24 h for 3 days) or placebo, in addition to the standard treatment. The primary outcome was the median time to platelet normalisation (defined as a platelet count ≥ 150 G/L). Efficacy and safety were assessed by intention-to-treat.
RESULTS
Overall, we enrolled 74 participants, including one who withdrew his/her consent. Seventy-three patients were further analyzed, 35 (48%) allocated to magnesium sulphate and 38 (52%) to placebo. The median time to platelet normalisation was 4 days (95% confidence interval [CI], 3-4) in the magnesium sulphate group and 4 days (95% CI 3-5) in the placebo group. The cause-specific hazard ratio of response was 0.93 (95% CI 0.58-1.48, p = 0.75). The number of patients with ≥ 1 serious adverse reactions was similar in the two groups. By day 90, four patients in the magnesium sulphate group and two patients in the placebo group had died (p = 0.42). The most frequent adverse event was low blood pressure occurring in 34% in the magnesium sulphate group and 29% in the placebo group (p = 0.80).
CONCLUSION
Among patients with TTP, the addition of magnesium sulphate to the standard of care did not result in a significant improvement in time to platelet normalisation.
Topics: Adult; Female; Humans; Male; Death; Double-Blind Method; Magnesium Sulfate; Platelet Count; Purpura, Thrombotic Thrombocytopenic; Treatment Outcome
PubMed: 37867165
DOI: 10.1007/s00134-023-07178-6