No. 376-Magnesium Sulphate for Fetal Neuroprotection

Objective: The objective is to provide guidelines for the use of antenatal magnesium sulphate for fetal neuroprotection of the preterm infant. Options: Antenatal magnesium sulphate administration should be considered for fetal neuroprotection when women present at <= 33 + 6 weeks with imminent preterm birth, defined as a high likelihood of birth because of active labour with cervical dilatation >= 4 cm, with or without preterm pre-labour rupture of membranes, and/or planned preterm birth for fetal or maternal indications. There are no other known fetal neuroprotective agents. Outcomes: The outcomes measured are the incidence of cerebral palsy (CP) and neonatal death. Evidence: Published literature was retrieved through searches of PubMed or Medline, CINAHL, and the Cochrane Library in December 2017, using appropriate controlled vocabulary and key words (magnesium sulphate, cerebral palsy, preterm birth). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 2017. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Benefits, harms, and costs: Antenatal magnesium sulphate for fetal neuroprotection reduces the risk of death or CP (relative risk [RR] 0.85; 95% confidence interval [CI] 0.74-0.98; 4 trials, 4446 infants), death or moderate-severe CP (RR 0.85; 95% CI 0.73-0.99; 3 trials, 4250 infants), any CP (RR 0.71; 95% CI 0.55-0.91; 4, trials, 4446 infants), moderate-to-severe CP (RR 0.60; 95% CI 0.43-0.84; 3 trials, 4250 infants), and substantial gross motor dysfunction (inability to walk without assistance) (RR 0.60; 95% CI 0.43-0.83; 3 trials, 4287 women) at 2 years of age. Results were consistent between trials and across the meta-analyses. There is no anticipated significant increase in health care-related costs because women eligible to receive antenatal magnesium sulphate will be judged to have imminent preterm birth. Validation: Australian National Clinical Practice Guidelines were published in March 2010 by the Antenatal Magnesium Sulphate for Neuroprotection Guideline Development Panel. Antenatal magnesium sulphate was recommended for fetal neuroprotection in the same dosage as recommended in these guidelines. However, magnesium sulphate was recommended only at <30 weeks gestation, based on 2 considerations. First, no single gestational age subgroup was considered to show a clear benefit. Second, in the face of uncertainty, the committee felt it was prudent to limit the impact of their clinical practice guidelines on resource allocation. In March 2010, the American College of Obstetricians and Gynecologists issued a Committee Opinion on magnesium sulphate for fetal neuroprotection. It stated that the available evidence suggests that magnesium sulfate given before anticipated early preterm birth reduces the risk of cerebral palsy in surviving infants. No official opinion was given on a gestational age cut-off, but it was recommended that physicians develop specific guidelines around the issues of inclusion criteria, dosage, concurrent tocolysis, and monitoring in accordance with 1 of the larger trials. Similarly, the World Health Organization also strongly recommends use of magnesium sulphate for fetal neuroprotection in its 2015 recommendations on interventions to improve preterm birth outcomes but cites further researching on dosing regimen and re-treatment. Sponsors: Canadian Institutes of Health Research (CIHR). Summary Statement: 1. Imminent preterm birth is defined as a high likelihood of birth due to 1 or both of the following conditions (II-2): Active labour with >= 4 cm of cervical dilation, with or without preterm pre-labour rupture of membranes. Planned preterm birth for fetal or maternal indications. Recommendations: 1. For women with imminent preterm birth (<= 33 + 6 weeks), antenatal magnesium sulphate administration should be considered for fetal neuroprotection (I-A). 2. Although there is controversy about upper gestational age, antenatal magnesium sulphate for fetal neuroprotection should be considered from viability to <= 33 + 6 weeks (II-1B). 3. If antenatal magnesium sulphate has been started for fetal neuroprotection based on a clinical diagnosis of imminent preterm birth, tocolysis is no longer indicated and should be discontinued (III-A). 4. Magnesium sulphate should be discontinued if delivery is no longer imminent or a maximum of 24 hours of therapy has been administered (II-2B). 5. For women with imminent preterm birth, antenatal magnesium sulphate for fetal neuroprotection should be administered as a 4-g intravenous loading dose, over 30 minutes, with or without a 1 g per hour maintenance infusion until birth (II-2B). 6. For planned preterm birth for fetal or maternal indications, magnesium sulphate should be started, ideally within 4 hours before birth, as a 4-g intravenous loading dose, over 30 minutes (II-2B). 7. There is insufficient evidence that a repeat course of antenatal magnesium sulphate for fetal neuroprotection should be administered (III-L). 8. Delivery should not be delayed in order to administer antenatal magnesium sulphate for fetal neuroprotection if there are maternal and/or fetal indications for emergency delivery (III-E). 9. When magnesium sulphate is given for fetal neuroprotection, maternity care providers should use existing protocols to monitor women who are receiving magnesium sulphate for preeclampsia/eclampsia (III-A). 10. Indications for fetal heart rate monitoring in women receiving antenatal magnesium sulphate for neuroprotection should follow the fetal surveillance recommendations of the Society of Obstetricians and Gynaecologists of Canada 2007 Fetal Health Surveillance: Antepartum and Intrapartum Consensus Guideline (III-A). 11. Decisions about neonatal resuscitation should not be influenced by whether or not the other received magnesium sulphate for fetal neuroprotection (II-I B).