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Caroline A Crowther - One of the best experts on this subject based on the ideXlab platform.

  • survey on use of antenatal Magnesium Sulphate for fetal neuroprotection prior to preterm birth in australia and new zealand ongoing barriers and enablers
    Australian & New Zealand Journal of Obstetrics & Gynaecology, 2020
    Co-Authors: Kate Gatman, Robyn May, Caroline A Crowther
    Abstract:

    BACKGROUND Clinical practice guidelines recommend the use of antenatal Magnesium Sulphate for fetal neuroprotection before preterm birth at <30 weeks' gestation. AIMS This survey assessed the use of antenatal Magnesium Sulphate for fetal neuroprotection to determine if use has changed since the previous survey in 2012, and to evaluate enablers and barriers to use. MATERIALS AND METHODS A questionnaire was sent to clinical leaders at 29 hospitals with a neonatal intensive care unit in Australia and New Zealand asking at what gestational ages Magnesium Sulphate was given, if use was audited and any enablers and barriers  to use. RESULTS Responses were received for 24 (83%) hospitals. The use of Magnesium Sulphate for fetal neuroprotection was reported as 89% (IQR 80-90%), an increase from 80% (IQR 53-90%) from the earlier survey. The majority of health professionals were reported as using Magnesium Sulphate at <30 weeks' gestation. The top enablers for use of Magnesium Sulphate were availability of pamphlets, posters, case record stickers and PowerPoint presentations. The main reasons as to why eligible women did not receive Magnesium Sulphate were imminent birth, the hospital being short staffed and the patient declined. The use of antenatal Magnesium Sulphate has been or is being audited in 11 (46%) of the hospitals. CONCLUSIONS Clinical leaders at institutions in Australia and New Zealand report that uptake in the use of Magnesium Sulphate for fetal neuroprotection has continued to increase since the earlier, bi-national survey in 2012. Barriers to the use of Magnesium Sulphate identified have institutional and consumer implications.

  • antenatal Magnesium Sulphate and adverse neonatal outcomes a systematic review and meta analysis
    PLOS Medicine, 2019
    Co-Authors: Emily Shepherd, Caroline A Crowther, Philippa Middleton, Anne Synnes, Rehana A Salam, Deepak Manhas, Maria Makrides
    Abstract:

    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.

  • assessing the neuroprotective benefits for babies of antenatal Magnesium Sulphate an individual participant data meta analysis
    PLOS Medicine, 2017
    Co-Authors: Lelia Duley, Stephane Marret, Caroline A Crowther, Philippa Middleton, Merryn Voysey, Lisa M Askie, Peter G Pryde, Lex W Doyle
    Abstract:

    Background Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal Magnesium Sulphate, compared with no Magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which Magnesium Sulphate treatment was received, or the dose and timing of the administration of Magnesium Sulphate. Methods and findings Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to Magnesium Sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [Magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of Magnesium Sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with Magnesium Sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to Magnesium Sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, Magnesium Sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which Magnesium Sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited. Conclusions Antenatal Magnesium Sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

  • assessing the neuroprotective benefits for babies of antenatal Magnesium Sulphate an individual participant data meta analysis
    PLOS Medicine, 2017
    Co-Authors: Caroline A Crowther, Lelia Duley, Stephane Marret, Philippa Middleton, Merryn Voysey, Lisa M Askie, Peter G Pryde, Lex W Doyle
    Abstract:

    © 2017 Crowther et al. Background: Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal Magnesium Sulphate, compared with no Magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which Magnesium Sulphate treatment was received, or the dose and timing of the administration of Magnesium Sulphate. Methods and findings: Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to Magnesium Sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [Magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of Magnesium Sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with Magnesium Sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to Magnesium Sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, Magnesium Sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which Magnesium Sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited. Conclusions: Antenatal Magnesium Sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

  • different treatment regimens of Magnesium Sulphate for tocolysis in women in preterm labour
    Cochrane Database of Systematic Reviews, 2015
    Co-Authors: Helen C Mcnamara, Caroline A Crowther, Julie Brown
    Abstract:

    Background Magnesium Sulphate has been used to inhibit preterm labour to prevent preterm birth. There is no consensus as to the safety profile of different treatment regimens with respect to dose, duration, route and timing of administration. Objectives To assess the efficacy and safety of alternative Magnesium Sulphate regimens when used as single agent tocolytic therapy during pregnancy. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2015) and reference lists of retrieved studies. Selection criteria Randomised trials comparing different Magnesium Sulphate treatment regimens when used as single agent tocolytic therapy during pregnancy in women in preterm labour. Quasi-randomised trials were eligible for inclusion but none were identified. Cross-over and cluster trials were not eligible for inclusion. Health outcomes were considered at the level of the mother, the infant/child and the health service. Intervention: intravenous or oral Magnesium Sulphate given alone for tocolysis. Comparison: alternative dosing regimens of Magnesium Sulphate given alone for tocolysis. Data collection and analysis Two review authors independently assessed trial eligibility and quality and extracted data. Main results Three trials including 360 women and their infants were identified as eligible for inclusion in this review. Two trials were rated as low risk of bias for random sequence generation and concealment of allocation. A third trial was assessed as unclear risk of bias for these domains but did not report data for any of the outcomes examined in this review. No trials were rated to be of high quality overall. Intravenous Magnesium Sulphate was administered according to low-dose regimens (4 g loading dose followed by 2 g/hour continuous infusion and/or increased by 1 g/hour hourly until successful tocolysis or failure of treatment), or high-dose regimens (4 g loading dose followed by 5 g/hour continuous infusion and increased by 1 g/hour hourly until successful tocolysis or failure of treatment, or 6 g loading dose followed by 2 g/hour continuous infusion and increased by 1 g/hour hourly until successful tocolysis or failure of treatment). There were no differences seen between high-dose Magnesium Sulphate regimens compared with low-dose Magnesium Sulphate regimens for the primary outcome of fetal, neonatal and infant death (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.12 to 1.56; one trial, 100 infants). Using the GRADE approach, the evidence for fetal, neonatal and infant death was considered to be VERY LOW quality. No data were reported for any of the other primary maternal and infant health outcomes (birth less than 48 hours after trial entry; composite serious infant outcome; composite serious maternal outcome). There were no clear differences seen between high-dose Magnesium Sulphate regimens compared with low-dose Magnesium Sulphate regimens for the secondary infant health outcomes of fetal death; neonatal death; and rate of hypocalcaemia, osteopenia or fracture; and secondary maternal health outcomes of rate of caesarean birth; pulmonary oedema; and maternal self-reported adverse effects. Pulmonary oedema was reported in two women given high-dose Magnesium Sulphate, but not in any of the women given low-dose Magnesium Sulphate. In a single trial of high and low doses of Magnesium Sulphate for tocolysis including 100 infants, the risk of respiratory distress syndrome was lower with use of a high-dose regimen compared with a low-dose regimen (RR 0.31, 95% CI 0.11 to 0.88; one trial, 100 infants). Using the GRADE approach, the evidence for respiratory distress syndrome was judged to be LOW quality. No difference was seen in the rate of admission to the neonatal intensive care unit. However, for those babies admitted, a high-dose regimen was associated with a reduction in the length of stay in the neonatal intensive care unit compared with a low-dose regimen (mean difference -3.10 days, 95% confidence interval -5.48 to -0.72). We found no data for the majority of our secondary outcomes. Authors' conclusions There are limited data available (three studies, with data from only two studies) comparing different dosing regimens of Magnesium Sulphate given as single agent tocolytic therapy for the prevention of preterm birth. There is no evidence examining duration of therapy, timing of therapy and the role for repeat dosing. Downgrading decisions for our primary outcome of fetal, neonatal and infant death were based on wide confidence intervals (crossing the line of no effect), lack of blinding and a limited number of studies. No data were available for any of our other important outcomes: birth less than 48 hours after trial entry; composite serious infant outcome; composite serious maternal outcome. The data are limited by volume and the outcomes reported. Only eight of our 45 pre-specified primary and secondary maternal and infant health outcomes were reported on in the included studies. No long-term outcomes were reported. Downgrading decisions for the evidence on the risk of respiratory distress were based on wide confidence intervals (crossing the line of no effect) and lack of blinding. There is some evidence from a single study suggesting a reduction in the length of stay in the neonatal intensive care unit and a reduced risk of respiratory distress syndrome where a high-dose regimen of Magnesium Sulphate has been used compared with a low-dose regimen. However, given that evidence has been drawn from a single study (with a small sample size), these data should be interpreted with caution. Magnesium Sulphate has been shown to be of benefit in a wide range of obstetric settings, although it has not been recommended for tocolysis. In clinical settings where health benefits are established, further trials are needed to address the lack of evidence regarding the optimal dose (loading dose and maintenance dose), duration of therapy, timing of therapy and role for repeat dosing in terms of efficacy and safety for mothers and their children. Ongoing examination of different regimens with respect to important health outcomes is required.

Philippa Middleton - One of the best experts on this subject based on the ideXlab platform.

  • antenatal Magnesium Sulphate and adverse neonatal outcomes a systematic review and meta analysis
    PLOS Medicine, 2019
    Co-Authors: Emily Shepherd, Caroline A Crowther, Philippa Middleton, Anne Synnes, Rehana A Salam, Deepak Manhas, Maria Makrides
    Abstract:

    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.

  • assessing the neuroprotective benefits for babies of antenatal Magnesium Sulphate an individual participant data meta analysis
    PLOS Medicine, 2017
    Co-Authors: Lelia Duley, Stephane Marret, Caroline A Crowther, Philippa Middleton, Merryn Voysey, Lisa M Askie, Peter G Pryde, Lex W Doyle
    Abstract:

    Background Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal Magnesium Sulphate, compared with no Magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which Magnesium Sulphate treatment was received, or the dose and timing of the administration of Magnesium Sulphate. Methods and findings Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to Magnesium Sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [Magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of Magnesium Sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with Magnesium Sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to Magnesium Sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, Magnesium Sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which Magnesium Sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited. Conclusions Antenatal Magnesium Sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

  • assessing the neuroprotective benefits for babies of antenatal Magnesium Sulphate an individual participant data meta analysis
    PLOS Medicine, 2017
    Co-Authors: Caroline A Crowther, Lelia Duley, Stephane Marret, Philippa Middleton, Merryn Voysey, Lisa M Askie, Peter G Pryde, Lex W Doyle
    Abstract:

    © 2017 Crowther et al. Background: Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal Magnesium Sulphate, compared with no Magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which Magnesium Sulphate treatment was received, or the dose and timing of the administration of Magnesium Sulphate. Methods and findings: Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to Magnesium Sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [Magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of Magnesium Sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with Magnesium Sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to Magnesium Sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, Magnesium Sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which Magnesium Sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited. Conclusions: Antenatal Magnesium Sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

  • barriers and enablers to implementing antenatal Magnesium Sulphate for fetal neuroprotection guidelines a study using the theoretical domains framework
    BMC Pregnancy and Childbirth, 2015
    Co-Authors: Emily Bain, Caroline A Crowther, Philippa Middleton, Pat Ashwood, Tanya Bubner, Emer Van Ryswyk, Lucy A Simmonds, Sally Reid
    Abstract:

    Strong evidence supports administration of Magnesium Sulphate prior to birth at less than 30 weeks’ gestation to prevent very preterm babies dying or developing cerebral palsy. This study was undertaken as part of The WISH (Working to Improve Survival and Health for babies born very preterm) Project, to assess health professionals’ self-reported use of antenatal Magnesium Sulphate, and barriers and enablers to implementation of 2010 Australian and New Zealand clinical practice guidelines. Semi-structured, one-to-one interviews were conducted with obstetric and neonatal consultants and trainees, and midwives in 2011 (n = 24) and 2012–2013 (n = 21) at the Women’s and Children’s Hospital, South Australia. Transcribed interview data were coded using the Theoretical Domains Framework (describing 14 domains related to behaviour change) for analysis of barriers and enablers. In 2012–13, health professionals more often reported ‘routinely’ or ‘sometimes’ administering or advising their colleagues to administer Magnesium Sulphate for fetal neuroprotection (86 % in 2012–13 vs. 46 % in 2011). ‘Knowledge and skills’, ‘memory, attention and decision processes’, ‘environmental context and resources’, ‘beliefs about consequences’ and ‘social influences’ were key domains identified in the barrier and enabler analysis. Perceived barriers were the complex administration processes, time pressures, and the unpredictability of preterm birth. Enablers included education for staff and women at risk of very preterm birth, reminders and ‘prompts’, simplified processes for administration, and influential colleagues. This study has provided valuable data on barriers and enablers to implementing Magnesium Sulphate for fetal neuroprotection, with implications for designing and modifying future behaviour change strategies, to ensure optimal uptake of this neuroprotective therapy for very preterm infants.

  • Magnesium Sulphate for preventing preterm birth in threatened preterm labour
    Cochrane Database of Systematic Reviews, 2014
    Co-Authors: Caroline A Crowther, Julie Brown, Christopher J D Mckinlay, Philippa Middleton
    Abstract:

    Background Magnesium Sulphate has been used in some settings as a tocolytic agent to inhibit uterine activity in women in preterm labour with the aim of preventing preterm birth. Objectives To assess the effects of Magnesium Sulphate therapy given to women in threatened preterm labour with the aim of preventing preterm birth and its sequelae. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (last searched 31 January 2014). Selection criteria Randomised controlled trials of Magnesium Sulphate as the only tocolytic, administered by any route, compared with either placebo, no treatment or alternative tocolytic therapy (not Magnesium Sulphate) to women considered to be in preterm labour. Data collection and analysis At least two review authors assessed trial eligibility and risk of bias and undertook data extraction independently. Main results The 37 included trials (total of 3571 women and over 3600 babies) were generally of moderate to high risk of bias. Antenatal Magnesium Sulphate was compared with either placebo, no treatment, or a range of alternative tocolytic agents. For the primary outcome of giving birth within 48 hours after trial entry, no significant differences were seen between women who received Magnesium Sulphate and women who did not (whether placebo/no alternative tocolytic drug, betamimetics, calcium channel blockers, cox inhibitors, prostaglandin inhibitors, or human chorionic gonadotropin) (19 trials, 1913 women). Similarly for the primary outcome of serious infant outcome, there were no significant differences between the infants exposed to Magnesium Sulphate and those not (whether placebo/no alternative tocolytic drug, betamimetics, calcium channel blockers, cox inhibitors, prostaglandin inhibitors, human chorionic gonadotropin or various tocolytic drugs) (18 trials; 2187 babies). No trials reported the outcome of extremely preterm birth. In the seven trials that reported serious maternal outcomes, no events were recorded. In the group treated with Magnesium Sulphate compared with women receiving antenatal placebo or no alternative tocolytic drug, a borderline increased risk of total death (fetal, neonatal, infant) was seen (risk ratio (RR) 4.56, 95% confidence interval (CI) 1.00 to 20.86; two trials, 257 babies); none of the comparisons between Magnesium Sulphate and other classes of tocolytic drugs showed differences for this outcome (10 trials, 991 babies). The outcomes of neonatal and/or infant deaths and of fetal deaths did not show differences between Magnesium Sulphate and no Magnesium Sulphate, whether compared with placebo/no alternative tocolytic drug, or any specific class of tocolytic drug. For most of the other secondary outcomes, there were no significant differences between Magnesium Sulphate and the control groups for risk of preterm birth (except for a significantly lower risk with Magnesium Sulphate when compared with barbiturates in one trial of 65 women), gestational age at birth, interval between trial entry and birth, other neonatal morbidities, or neurodevelopmental outcomes. Duration of neonatal intensive care unit stay was significantly increased in the Magnesium Sulphate group compared with the calcium channel blocker group, but not when compared with cox inhibitors or prostaglandin inhibitors. No maternal deaths were reported in the four trials reporting this outcome. Significant differences between Magnesium Sulphate and controls were not seen for maternal adverse events severe enough to stop treatment, except for a significant benefit of Magnesium Sulphate compared with betamimetics in a single trial. Authors' conclusions Magnesium Sulphate is ineffective at delaying birth or preventing preterm birth, has no apparent advantages for a range of neonatal and maternal outcomes as a tocolytic agent and its use for this indication may be associated with an increased risk of total fetal, neonatal or infant mortality (in contrast to its use in appropriate groups of women for maternal, fetal, neonatal and infant neuroprotection where beneficial effects have been demonstrated).

Lelia Duley - One of the best experts on this subject based on the ideXlab platform.

  • assessing the neuroprotective benefits for babies of antenatal Magnesium Sulphate an individual participant data meta analysis
    PLOS Medicine, 2017
    Co-Authors: Caroline A Crowther, Lelia Duley, Stephane Marret, Philippa Middleton, Merryn Voysey, Lisa M Askie, Peter G Pryde, Lex W Doyle
    Abstract:

    © 2017 Crowther et al. Background: Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal Magnesium Sulphate, compared with no Magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which Magnesium Sulphate treatment was received, or the dose and timing of the administration of Magnesium Sulphate. Methods and findings: Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to Magnesium Sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [Magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of Magnesium Sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with Magnesium Sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to Magnesium Sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, Magnesium Sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which Magnesium Sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited. Conclusions: Antenatal Magnesium Sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

  • assessing the neuroprotective benefits for babies of antenatal Magnesium Sulphate an individual participant data meta analysis
    PLOS Medicine, 2017
    Co-Authors: Lelia Duley, Stephane Marret, Caroline A Crowther, Philippa Middleton, Merryn Voysey, Lisa M Askie, Peter G Pryde, Lex W Doyle
    Abstract:

    Background Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal Magnesium Sulphate, compared with no Magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which Magnesium Sulphate treatment was received, or the dose and timing of the administration of Magnesium Sulphate. Methods and findings Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to Magnesium Sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [Magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of Magnesium Sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with Magnesium Sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to Magnesium Sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, Magnesium Sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which Magnesium Sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited. Conclusions Antenatal Magnesium Sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

  • clinical pharmacokinetic properties of Magnesium Sulphate in women with pre eclampsia and eclampsia
    British Journal of Obstetrics and Gynaecology, 2016
    Co-Authors: Babasola O Okusanya, Lelia Duley, Olufemi T Oladapo, Qian Long, Pisake Lumbiganon, Guillermo Carroli, Zahida Qureshi, Joao Paulo Souza, A M Gulmezoglu
    Abstract:

    Background The pharmacokinetic basis of Magnesium Sulphate (MgSO 4) dosing regimens for eclampsia prophylaxis and treatment is not clearly established.

  • Magnesium Sulphate versus diazepam for eclampsia
    Cochrane Database of Systematic Reviews, 2010
    Co-Authors: Lelia Duley, David J Hendersonsmart, Godfrey Ja Walker, Doris Chou
    Abstract:

    Background Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains a rare but serious complication of pregnancy. A number of different anticonvulsants are used to control eclamptic fits and to prevent further fits. Objectives The objective of this review was to assess the effects of Magnesium Sulphate compared with diazepam when used for the care of women with eclampsia. Magnesium Sulphate is compared with phenytoin and with lytic cocktail in other Cochrane reviews. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2010) and CENTRAL (2010, Issue 3). Selection criteria Randomised trials comparing Magnesium Sulphate (intravenous or intramuscular administration) with diazepam for women with a clinical diagnosis of eclampsia. Data collection and analysis Two authors assessed and extracted data independently. Main results We have included seven trials, involving 1396 women. Three trials (1030 women) were good quality. Magnesium Sulphate was associated with a reduction in maternal death (seven trials;1396 women; risk ratio (RR) 0.59, 95% confidence interval (CI) 0.38 to 0.92) and recurrence of seizures (seven trials;1390 women; RR 0.43, 95% CI 0.33 to 0.55) compared to diazepam. There were no clear differences in other measures of maternal morbidity. There was no clear difference in perinatal mortality (four trials; 788 infants; RR 1.04, 95% CI 0.81 to 1.34) or neonatal mortality (four trials; 759 infants; RR 1.18, 95% CI 0.75 to 1.84). In the Magnesium Sulphate group, fewer liveborn babies had an Apgar score less than seven at one minute (two trials; 597 babies; RR 0.75, 95% CI 0.65 to 0.87) or at five minutes (RR 0.70, 95% CI 0.54 to 0.90), and fewer appeared to need intubation at the place of birth (two trials; 591 infants; RR 0.67, 95% CI 0.45 to 1.00). There was no difference in admission to a special care nursery (four trials; 834 infants; RR 0.91, 95% CI 0.79 to 1.05), but fewer babies in the Magnesium Sulphate group had a length of stay more than seven days (three trials 631 babies; RR 0.66, 95% CI 0.46 to 0.96). Authors' conclusions Magnesium Sulphate for women with eclampsia reduces the risk ratio of maternal death and of recurrence of seizures, compared with diazepam.

  • Magnesium Sulphate and other anticonvulsants for women with pre eclampsia
    Cochrane Database of Systematic Reviews, 2010
    Co-Authors: Lelia Duley, David J Hendersonsmart, Metin A Gulmezoglu, Doris Chou
    Abstract:

    Background Eclampsia, the occurrence of a seizure (fit) in association with pre-eclampsia, is rare but potentially life-threatening. Magnesium Sulphate is the drug of choice for treating eclampsia. This review assesses its use for preventing eclampsia. Objectives To assess the effects of Magnesium Sulphate, and other anticonvulsants, for prevention of eclampsia. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (4 June 2010), and the Cochrane Central Register of Controlled Trials Register (The Cochrane Library 2010, Issue 3). Selection criteria Randomised trials comparing anticonvulsants with placebo or no anticonvulsant, or comparisons of different drugs, for pre-eclampsia. Data collection and analysis Two authors assessed trial quality and extracted data independently. Main results We included 15 trials. Six (11,444 women) compared Magnesium Sulphate with placebo or no anticonvulsant: Magnesium Sulphate more than a halved the risk of eclampsia (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.29 to 0.58; number needed to treat for an additional beneficial outcome (NNTB) 100, 95% CI 50 to 100), with a non-significant reduction in maternal death (RR 0.54, 95% CI 0.26 to 1.10) but no clear difference in serious maternal morbidity (RR 1.08, 95% CI 0.89 to 1.32). It reduced the risk of placental abruption (RR 0.64, 95% CI 0.50 to 0.83; NNTB 100, 95% CI 50 to 1000), and increased caesarean section (RR 1.05, 95% CI 1.01 to 1.10). There was no clear difference in stillbirth or neonatal death (RR 1.04, 95% CI 0.93 to 1.15). Side effects, primarily flushing, were more common with Magnesium Sulphate (24% versus 5%; RR 5.26, 95% CI 4.59 to 6.03; number need to treat for an additional harmful outcome (NNTH) 6, 95% CI 5 to 6). Follow-up was reported by one trial comparing Magnesium Sulphate with placebo: for 3375 women there was no clear difference in death (RR 1.79, 95% CI 0.71 to 4.53) or morbidity potentially related to pre-eclampsia (RR 0.84, 95% CI 0.55 to 1.26) (median follow-up 26 months); for 3283 children exposed in utero there was no clear difference in death (RR 1.02, 95% CI 0.57 to 1.84) or neurosensory disability (RR 0.77, 95% CI 0.38 to 1.58) at age 18 months. Magnesium Sulphate reduced eclampsia compared to phenytoin (three trials, 2291 women; RR 0.08, 95% CI 0.01 to 0.60) and nimodipine (one trial, 1650 women; RR 0.33, 95% CI 0.14 to 0.77). Authors' conclusions Magnesium Sulphate more than halves the risk of eclampsia, and probably reduces maternal death. There is no clear effect on outcome after discharge from hospital. A quarter of women report side effects with Magnesium Sulphate.

Lex W Doyle - One of the best experts on this subject based on the ideXlab platform.

  • translating antenatal Magnesium Sulphate neuroprotection for infants born 28 weeks gestation into practice a geographical cohort study
    Australian & New Zealand Journal of Obstetrics & Gynaecology, 2021
    Co-Authors: Lex W Doyle, Alicia J Spittle, Joy E Olsen, Amanda Kwong, Rosemarie A Boland, Katherine J Lee, Peter J Anderson
    Abstract:

    BACKGROUND: Magnesium Sulphate was introduced for fetal neuroprotection in Australia in 2010. The aim of this study was to determine how often antenatal Magnesium Sulphate is used currently and its association with cerebral palsy in children born <28 weeks' gestation. MATERIALS AND METHODS: Participants comprised all survivors born <28 weeks' gestational age in the state of Victoria in 2016-17, and earlier, in 1991-92, 1997, 2005. Rates of cerebral palsy, diagnosed at two years for the 2016-17 cohort, and at eight years in the earlier cohorts, were compared across eras. Within 2016-17, the proportions of children exposed to antenatal Magnesium Sulphate were determined, and rates of cerebral palsy were compared between those with and without exposure to Magnesium Sulphate. RESULTS: Overall, cerebral palsy was present in 6% (11/171) of survivors born in 2016-17, compared with 12% (62/499) of survivors born in the three earlier eras (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.25-0.94; P = 0.032). Data were available for 213/215 (99%) survivors born in 2016-17, of whom 147 (69%) received Magnesium Sulphate. Data on cerebral palsy at two years were available for 171 (80%) survivors with Magnesium data. Cerebral palsy was present in 5/125 (4%) children exposed to Magnesium Sulphate and in 6/46 (13%) of those not exposed (OR 0.28, 95% CI 0.08-0.96; P = 0.043). CONCLUSIONS: Antenatal Magnesium Sulphate is being translated into clinical practice for infants born <28 weeks' gestation, but there is room for improvement. It is associated with lower rates of cerebral palsy in survivors.

  • assessing the neuroprotective benefits for babies of antenatal Magnesium Sulphate an individual participant data meta analysis
    PLOS Medicine, 2017
    Co-Authors: Lelia Duley, Stephane Marret, Caroline A Crowther, Philippa Middleton, Merryn Voysey, Lisa M Askie, Peter G Pryde, Lex W Doyle
    Abstract:

    Background Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal Magnesium Sulphate, compared with no Magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which Magnesium Sulphate treatment was received, or the dose and timing of the administration of Magnesium Sulphate. Methods and findings Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to Magnesium Sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [Magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of Magnesium Sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with Magnesium Sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to Magnesium Sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, Magnesium Sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which Magnesium Sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited. Conclusions Antenatal Magnesium Sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

  • assessing the neuroprotective benefits for babies of antenatal Magnesium Sulphate an individual participant data meta analysis
    PLOS Medicine, 2017
    Co-Authors: Caroline A Crowther, Lelia Duley, Stephane Marret, Philippa Middleton, Merryn Voysey, Lisa M Askie, Peter G Pryde, Lex W Doyle
    Abstract:

    © 2017 Crowther et al. Background: Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal Magnesium Sulphate, compared with no Magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which Magnesium Sulphate treatment was received, or the dose and timing of the administration of Magnesium Sulphate. Methods and findings: Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to Magnesium Sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [Magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of Magnesium Sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with Magnesium Sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to Magnesium Sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, Magnesium Sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which Magnesium Sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited. Conclusions: Antenatal Magnesium Sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

  • Magnesium Sulphate for fetal neuroprotection
    Journal of obstetrics and gynaecology Canada, 2011
    Co-Authors: Laura A Magee, Lex W Doyle, Anne Synnes, Diane Sawchuck, Melanie Basso, Peter Von Dadelszen, Joan Crane, William Ehman, Robert Gagnon, William A Grobman
    Abstract:

    Abstract Objective To provide guidelines for the use of antenatal Magnesium Sulphate (MgSO 4 ) for fetal neuroprotection of the preterm infant. Options Antenatal MgSO4 administration should be considered for fetal neuroprotection when women present at ≤ 31+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 May 2010, 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 August 2010. 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" (RR 0.85; 95% CI 0.74 to 0.98; 4 trials, 4446 infants), "death or moderatesevere CP" (RR 0.85; 95% CI 0.73 to 0.99; 3 trials, 4250 infants), "any CP" (RR 0.71; 95% CI 0.55 to 0.91; 4, trials, 4446 infants), "moderate-to-severe CP" (RR 0.60; 95% CI 0.43 to 0.84; 3 trials, 4250 infants), and "substantial gross motor dysfunction" (inability to walk without assistance) (RR 0.60; 95% CI 0.43 to 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 MgSO4 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 MgSO 4 was recommended for fetal neuroprotection in the same dosage as recommended in these guidelines. However, MgSO 4 was recommended only at 4 for fetal neuroprotection. It stated that, "the available evidence suggests that Magnesium Sulphate 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 one of the larger trials. Sponsors Canadian Institutes of Health Research (CIHR).

  • Magnesium Sulphate for women at risk of preterm birth for neuroprotection of the fetus
    Cochrane Database of Systematic Reviews, 2009
    Co-Authors: Lex W Doyle, Stephane Marret, Caroline A Crowther, Philippa Middleton, Dwight J Rouse
    Abstract:

    Background Epidemiological and basic science evidence suggests that Magnesium Sulphate before birth may be neuroprotective for the fetus. Objectives To assess the effects of Magnesium Sulphate as a neuroprotective agent when given to women considered at risk of preterm birth. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2008). Selection criteria Randomised controlled trials of antenatal Magnesium Sulphate therapy in women threatening or likely to give birth at less than 37 weeks' gestational age. For one subgroup analysis, studies were broadly categorised by the primary intent of the study into "neuroprotective intent", or "other intent (maternal neuroprotective - pre-eclampsia)", or "other intent (tocolytic)". Data collection and analysis At least two authors assessed trial eligibility and quality, and extracted data. Main results Five trials (6145 babies) were eligible for this review. Antenatal Magnesium Sulphate therapy given to women at risk of preterm birth substantially reduced the risk of cerebral palsy in their child (relative risk (RR) 0.68; 95% Confidence interval (CI) 0.54 to 0.87; five trials; 6145 infants). There was also a significant reduction in the rate of substantial gross motor dysfunction (RR 0.61; 95% CI 0.44 to 0.85; four trials; 5980 infants). No statistically significant effect of antenatal Magnesium Sulphate therapy was detected on paediatric mortality (RR 1.04; 95% CI 0.92 to 1.17; five trials; 6145 infants), or on other neurological impairments or disabilities in the first few years of life. Overall there were no significant effects of antenatal Magnesium therapy on combined rates of mortality with cerebral palsy, although there were significant reductions for the neuroprotective groups RR 0.85; 95% CI 0.74 to 0.98; four trials; 4446 infants, but not for the other intent subgroups. There were higher rates of minor maternal side effects in the Magnesium groups, but no significant effects on major maternal complications. Authors' conclusions The neuroprotective role for antenatal Magnesium Sulphate therapy given to women at risk of preterm birth for the preterm fetus is now established. The number of women needed to be treated to benefit one baby by avoiding cerebral palsy is 63 (95% confidence interval 43 to 155). Given the beneficial effects of Magnesium Sulphate on substantial gross motor function in early childhood, outcomes later in childhood should be evaluated to determine the presence or absence of later potentially important neurological effects, particularly on motor or cognitive function.

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  • assessing the neuroprotective benefits for babies of antenatal Magnesium Sulphate an individual participant data meta analysis
    PLOS Medicine, 2017
    Co-Authors: Lelia Duley, Stephane Marret, Caroline A Crowther, Philippa Middleton, Merryn Voysey, Lisa M Askie, Peter G Pryde, Lex W Doyle
    Abstract:

    Background Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal Magnesium Sulphate, compared with no Magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which Magnesium Sulphate treatment was received, or the dose and timing of the administration of Magnesium Sulphate. Methods and findings Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to Magnesium Sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [Magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of Magnesium Sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with Magnesium Sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to Magnesium Sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, Magnesium Sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which Magnesium Sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited. Conclusions Antenatal Magnesium Sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

  • assessing the neuroprotective benefits for babies of antenatal Magnesium Sulphate an individual participant data meta analysis
    PLOS Medicine, 2017
    Co-Authors: Caroline A Crowther, Lelia Duley, Stephane Marret, Philippa Middleton, Merryn Voysey, Lisa M Askie, Peter G Pryde, Lex W Doyle
    Abstract:

    © 2017 Crowther et al. Background: Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal Magnesium Sulphate, compared with no Magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which Magnesium Sulphate treatment was received, or the dose and timing of the administration of Magnesium Sulphate. Methods and findings: Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to Magnesium Sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [Magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of Magnesium Sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with Magnesium Sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to Magnesium Sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, Magnesium Sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which Magnesium Sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited. Conclusions: Antenatal Magnesium Sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

  • Magnesium Sulphate for women at risk of preterm birth for neuroprotection of the fetus
    Cochrane Database of Systematic Reviews, 2009
    Co-Authors: Lex W Doyle, Stephane Marret, Caroline A Crowther, Philippa Middleton, Dwight J Rouse
    Abstract:

    Background Epidemiological and basic science evidence suggests that Magnesium Sulphate before birth may be neuroprotective for the fetus. Objectives To assess the effects of Magnesium Sulphate as a neuroprotective agent when given to women considered at risk of preterm birth. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2008). Selection criteria Randomised controlled trials of antenatal Magnesium Sulphate therapy in women threatening or likely to give birth at less than 37 weeks' gestational age. For one subgroup analysis, studies were broadly categorised by the primary intent of the study into "neuroprotective intent", or "other intent (maternal neuroprotective - pre-eclampsia)", or "other intent (tocolytic)". Data collection and analysis At least two authors assessed trial eligibility and quality, and extracted data. Main results Five trials (6145 babies) were eligible for this review. Antenatal Magnesium Sulphate therapy given to women at risk of preterm birth substantially reduced the risk of cerebral palsy in their child (relative risk (RR) 0.68; 95% Confidence interval (CI) 0.54 to 0.87; five trials; 6145 infants). There was also a significant reduction in the rate of substantial gross motor dysfunction (RR 0.61; 95% CI 0.44 to 0.85; four trials; 5980 infants). No statistically significant effect of antenatal Magnesium Sulphate therapy was detected on paediatric mortality (RR 1.04; 95% CI 0.92 to 1.17; five trials; 6145 infants), or on other neurological impairments or disabilities in the first few years of life. Overall there were no significant effects of antenatal Magnesium therapy on combined rates of mortality with cerebral palsy, although there were significant reductions for the neuroprotective groups RR 0.85; 95% CI 0.74 to 0.98; four trials; 4446 infants, but not for the other intent subgroups. There were higher rates of minor maternal side effects in the Magnesium groups, but no significant effects on major maternal complications. Authors' conclusions The neuroprotective role for antenatal Magnesium Sulphate therapy given to women at risk of preterm birth for the preterm fetus is now established. The number of women needed to be treated to benefit one baby by avoiding cerebral palsy is 63 (95% confidence interval 43 to 155). Given the beneficial effects of Magnesium Sulphate on substantial gross motor function in early childhood, outcomes later in childhood should be evaluated to determine the presence or absence of later potentially important neurological effects, particularly on motor or cognitive function.

  • antenatal Magnesium Sulphate neuroprotection in the preterm infant
    Seminars in Fetal & Neonatal Medicine, 2007
    Co-Authors: Stephane Marret, Lex W Doyle, Caroline A Crowther, Philippa Middleton
    Abstract:

    Very preterm infants have high rates of neurological impairments and disabilities. These rates have not diminished as the survival rates have improved. Basic science research suggests that Magnesium Sulphate before birth can be neuroprotective for the preterm fetus. Some, but not all, observational studies in humans also suggest a protective effect of antenatal Magnesium Sulphate on cerebral palsy. Four randomised controlled trials of antenatal Magnesium Sulphate have reported long-term neurological effects in surviving infants, but only one of these was designed specifically to evaluate the long-term effects of treatment. These studies found that, overall, antenatal Magnesium Sulphate therapy had no significant effect on paediatric mortality or neurological outcomes in the first few years of life, including cerebral palsy, but it was found to lower the rate of motor problems at 2 years of age in one study. The role for antenatal Magnesium Sulphate therapy as a neuroprotective agent for the preterm fetus is not yet established.