SOGC Clinical Practice Guideline
No. 376-Magnesium Sulphate for Fetal Neuroprotection

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Abstract

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 ≥4cm, 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 Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment–related agencies, clinical practice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 (Table1).

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 2years 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 ≥4cm 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 24hours 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 1g 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 4hours 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).

Section snippets

The Importance of Preterm Birth

The Canadian preterm birth rate was 7.8% of live births in 2013, with births1 at <32 weeks representing 1.2 % of live births in Canada. The survival of infants born preterm has improved with interventions such as antenatal corticosteroids and surfactant. However, survival has been associated with substantial risk of medical and neurodevelopmental impairment.

Clinically important adverse neurological outcomes associated with preterm birth include CP and motor impairment.2 Other adverse outcomes

TRANSPORT

As most maternal transports do not involve women in imminent preterm labour, magnesium administration would usually not be indicated on a maternal transport. Decisions regarding treatment with magnesium should be made in consultation with the receiving centre, on a case-by-case basis.

DRUG INTERACTIONS

When tocolysis has been employed to attempt to arrest preterm labour, magnesium sulphate can be used once tocolysis has been discontinued because delivery is considered imminent. If nifedipine has been used for

CLINICAL PRACTICE GUIDELINES AND COMMITTEE OPINION

Australian National Clinical Practice Guidelines68 were published in March 2010 by the Antenatal Magnesium Sulphate for Neuroprotection Guideline Development Panel. They recommended antenatal magnesium sulphate for fetal neuroprotection (excellent evidence) in the same dosage as recommended in these guidelines. However, magnesium was recommended only at <30 weeks gestation (good evidence) on the basis of 2 considerations. First, no 1 gestational age subgroup (of the <34-, <33-, <32-, and

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    This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be reproduced in any form without prior written permission of the publisher.

    All people have the right and responsibility to make informed decisions about their care in partnership with their health care providers. In order to facilitate informed choice, patients should be provided with information and support that is evidence-based, culturally appropriate and tailored to their needs.

    This guideline was written using language that places women at the centre of care. That said, the SOGC is committed to respecting the rights of all people - including transgender, gender non-binary, and intersex people - for whom the guideline may apply. We encourage healthcare providers to engage in respectful conversation with patients regarding their gender identity as a critical part of providing safe and appropriate care. The values, beliefs and individual needs of each patient and their family should be sought and the final decision about the care and treatment options chosen by the patient should be respected.

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    © 2018 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.