Magnesiumsulfaat

Study

Method

Patients

Intervention, controls and outcomes

Results

Results critical appraisal

Bain (2012)

Design

Cochrane systematic review

Source of funding

ARCH, Robinson Institute, The University of Adelaide, Australia.

E Bain is supported by the Jeffrey Robinson Honours Scholarship.

Australian Government, Department of Health and Ageing, Australia.

Search date

31 December 2011

Searched databases

The Cochrane Pregnancy and Childbirth Group's Trials Register

Included study designs

Randomised trials, quasi-randomised trials and those with a crossover design were excluded.

Number of included studies

0

Women expected to give birth preterm (before 37 weeks)

All randomised comparisons of different antenatal magnesiumsulphate

regimens for neuroprotection of the fetus given to women at

risk of preterm birth.

Comparisons could include different routes of administration, different loading or maintenance doses, different

durations of therapy, timings of therapy, and whether re-treatment was permitted.

No studies included.

Crowther (2014)

Design

Cochrane systematic review

Source of funding

ARCH, Robinson Institute/School of Paediatrics and Reproductive health, The University of Adelaide, Australia. • Department of Obstetrics and Gynaecology, University of Melbourne, Australia. • Liggins Institute, University of Auckland, New Zealand.

National Health and Medical Research Council, (NHMRC), Australia.

Search date

31 January 2014

Searched databases

Cochrane Pregnancy and Childbirth Group's Trials Register

Included study designs

All published, unpublished and ongoing randomised trials that compared outcomes for women in threatened preterm labour given magnesium sulphate alone for tocolysis, with outcomes in controls, with or without placebo or alternative tocolytic drug therapy (not magnesium sulphate), reported as papers or abstracts. Quasi-randomised trials were included.

Number of included studies

37, 1 study reported Apgar-score (but included very preterm women), 5 studies reported admission to neonatal intensive care unit.

Women considered to be in preterm labour given magnesium sulphate to reduce their risk of preterm birth.

3571 women and over 3600 babies were included.

Outcome: Apgar-score:

Floyd, 1992: gestational age range: 20-34 weeks’ gestation. Included were 90 women in preterm labour.

Outcome: admission to NICU:

Cox, 1990: no other tocolytic drug (placebo). Gestational age range: 24-34 weeks’ gestation.

Larmon, 1999; Lyell, 2007: calcium channel blockers. Larmon: gestational age range: between 24-34 week; Lyell: 24 to 33 6/7 weeks’ GA.

McWorther, 2004: Cox inhibitors. 22 to 34 weeks’ gestation.

Lorzadeh, 2007: HCG. 22 to 35 weeks’ GA.

Intervention/control:

Magnesium sulphate as the only tocolytic, administered by any route, compared with either placebo, no treatment or alternative tocolytic therapy (not magnesium sulphate)

• Apgar-score less than seven at five minutes
• Admission to neonatal intensive care
• Use of assisted ventilation

No relevant studies included (only results available from studies with very preterm children).

McDonald (2012)

Design

Systematic review of Cohort, before-and-after, and serial cross-sectional studies.

Source of funding

S.D.M. is supported by a Canadian Institutes of Health Research (CIHR) New Investigator Award. CIHR did not have any role in the analyses, report writing, interpretation of data, or decision to submit the manuscript.

Search date

January 1990-July 2010

Searched databases

EMBASE and MEDLINE

Included study designs

Cohort, before-and-after, and serial cross-sectional studies.

Number of included studies

6, but none were relevant

Women with eclampsia who received magnesium sulfate or another anticonvulsant, and women with pre-eclampsia who received magnesium sulfate or no anticonvulsant

Outcome: admission to a special care nursery.

No relevant studies included.

Pratt (2016)

Design

Systematic review of non-randomized studies.

Source of funding

World Health Organization and a grant from Merck for Mothers. The funders were not involved in the design, data collection, analysis, interpretation or writing of this report, or in the decision to submit the article for publication.

Search date

16 October 2013, and updated on 26 September 2014.

Searched databases

Medline, EMBASE, Popline, CINAHL, Global Health Library, African Index Medicus, Biological abstract, BIOSIS and reference lists of eligible studies.

Included study designs

Quasi-RCTs, cohort, case-control and cross-sectional studies.

Number of included studies

5, but none were relevant

The population of interest was women

with preeclampsia or eclampsia, regardless of single or multiple pregnancy, or time of onset of preeclampsia (antepartum, intrapartum or postpartum).

Intervention/control:

Alternative magnesium sulfate regimens.

Outcomes:

Secondary outcomes included neonatal morbidity (e.g. Apgar-score <7 at 5 minutes, intubation, admission to special care nursery).

No relevant outcomes reported.

Nguyen (2013)

Design

Cochrane systematic review

Source of funding

The University of Adelaide, Australia and the National Health and Medical Research Council, Australia.

Search date

31 July 2012

Searched databases

Cochrane Pregnancy and Childbirth Group’s Trial Register, containing trials identified from: 1. monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL); 2. weekly searches of MEDLINE; 3. weekly searches of EMBASE; 4. handsearches of 30 journals and the proceedings of major conferences; 5. weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.

Included study designs

Randomized controlled trials. Cluster-randomised trials were included, cross-over trials, quasi-randomised trials and abstracts only were excluded.

Number of included studies

1 (Witlin, 1997)

135 Women with mild pre-eclampsia (high blood pressure and/or protein in the urine) administered antenatal magnesium sulphate at a gestational age of 37 weeks or later.

1 trial was included (Witlin, 1997).

Intervention

Magnesium sulphate

Controls

Placebo or no treatment

Relevant outcomes:

-Apgar-scores of less than seven at five minutes

-Endotracheal intubation for resuscitation at birth

Apgar-score: no significant difference between magnesium sulphate and placebo in Apgar-score less than seven at five minutes (risk ratio (RR) 0.51; 95% confidence interval (CI) 0.05 to 5.46

Any of the other secondary review outcomes for the infant/child were not reported.

-Unclear risk of reporting bias, with no access to the trial’s protocol. The primary outcomes relevant to the review were not reported in the included study.

-The trial was stopped at 68% of the planned enrolment, following a single interim analysis that determined only 37 women in each group were needed to rule out that magnesium sulphate was associated with a 33% increase in the length of labour

Duley (2013)

Design

Cochrane systematic review

Source of funding

Medical Research Council, UK. • Resource Centre for Randomised Trials, Oxford, UK.

National Institute for Health Research, UK

Search date

9 January 2013

Searched databases

Cochrane Pregnancy and Childbirth Group Trials Register

Included study designs

Randomised trials.

Number of included studies

Thirty-five trials (3573 women) with 15 comparisons were included.

Women with severe hypertension during pregnancy.

Only 1 trial reported relevant outcomes: Nimodipine (2003), but this study was also included in Duley (2010).

Any comparison of one antihypertensive drug with another regardless of dose, route of administration or duration of therapy.

Relevant outcomes:

*Apgar-score at five minutes: low (less than seven) and very low (less than four) or lowest reported.

*Admission to special care nursery, length of stay, *Endotracheal intubation

No new studies included.

Duley (2011) / Alternative

Design

Cochrane systematic review

Source of funding

University of Leeds, UK

Search date

June 2010

Searched databases

Cochrane Pregnancy and Childbirth Group’s Trial Register

Included study designs

Randomised trials comparing different regimens for administration of magnesium sulphate

Number of included studies

6 (Begum 2002; Shilva 2007; Suneja 2008; Chissell 1994; Fontenot 2008; Ehrenberg 2004 and 2006)

Any women with a diagnosis of pre-eclampsia or eclampsia, irrespective

of whether this is during pregnancy, in labour or after

delivery, and regardless of whether the pregnancy was single or multiple.

1 of the included studies reported relevant outcomes:

Shilva, India, 2007:

- 50 women with antepartum eclampsia.

-Treatment of eclampsia: lower dose regimens versus standard dose regimens

-Intervention: 4 g IV + 6 g IM loading dose MgSO4, then 2.5 g IM every 4 hours for 24 hours. Control: 4 g IV + 8 g IM MgSO4 loading dose, then 4 g IM every 4 hours for 24 hours.

Intervention

Magnesium sulphate

Controls

Alternate regimen for administration of Magnesium sulphate. Comparisons could include different dose regimens, whether the intramuscular or intravenous route was used for maintenance therapy, and different durations of therapy.

Relevant outcomes

-Hypotension

-Admission to a special care nursery

Shilva, India, 2007:

Women allocated the lower dose, rather than standard, regimen were less likely to have babies who developed neonatal hypotonia, although the confidence intervals were wide (RR 0.13, 95% CI 0.02 to 0.98).

Admission to special care baby unit (RR 2.36, 95% CI 0.53-10.58),

In the study of Shilva in addition the Apgar-score was reported:

<7 at 1 min 7 (28) versus 8 (32) (p=0.73)

<7 at 5 min 4 (16) versus 4 (16) (p=0.73)

Shilva, 2007:

-No information about concealment of allocation.

- Blinding not mentioned, but in view of the intervention it is unlikely there was blinding of the clinician. Blinding of participant would have been possible, as would blinding of assessment for some outcomes.

-The gestational age of the children was not mentioned. It may have been very preterms.

Duley (2010) / anticonvulsants

Design

Cochrane systematic review

Source of funding

Centre for Perinatal Health Services Research, University of Sydney, Australia; HRP-UNDP/UNFPA/WHO/World Bank Special Programme in Human Reproduction, Geneva, Switzerland; Department for International Development, UK. • Medical Research Council, UK.

Search date

June 2010

Searched databases

Cochrane Pregnancy and Childbirth Group’s Trials Register

Included study designs

Randomised trials. Quasi-randomized trials were excluded.

Number of included studies

15 (Rudnicki, 2000; Sharma 2008; Magpie Trial 2002; Adeeb 1994; Walss 1992; Vargas 1998; Nimodipine 2003; Moodley 1994; Anthony 1998; Chen 1995; Atkinson 1995; Friedman 1993; Witlin 1997; Livingston 2002; Texas USA 1995)

Any women with pre-eclampsia, regardless of whether before or after delivery, whether a singleton or multiple pregnancy, or whether

an anticonvulsant had been given before trial entry.

3 of the included studies reported relevant outcomes:

Texas (USA, 1995):

2138 women with BP>/=140/90 mmHg MgSO4: 10 g (50% solution) IM (5 g in each buttock), then 5 g IM every 4 hours. If severe pre-eclampsia, an additional 4 g IV (20% solution) before the first IM dose. Gestational age not described.

Nimodipine SG (2003):

-Recruitment at 14 hospitals in 8 countries

-1750 women with PE

Magpie Trial (2002)

Multicentre trial, 175 centres in 33 countries, 4162 women. Gestational age at birth: 80% >34 wks.

Comparison of Magnesium sulphate and other anticonvulsants with placebo or no anticonvulsant, or comparisons of different drugs.

Relevant outcomes

-Apgar-score at five minutes: low (less than seven) and very low (less than four) or lowest reported;

-Endotracheal intubation

-Hypotonia

-Intubation

-Hypotension

-Admission to a special care baby unit

Magnesium sulphate versus phenytoin (Texas, USA, 1995):

No clear differences between the groups in the other reported measures of neonatal morbidity: Apgar at five minutes (RR 0.58, 95%CI 0.26-1.30).

Magnesium sulphate versus nimodipine (Nimodipine, 2003):

Hypotonia (RR=1.78; 0.91-3.46), intubation (RR=1.37; 0.91-2.05) and hypotension (RR=0.32; 0.06-1.58): there were no clear differences between the groups for any of these outcomes.

Magnesium sulphate versus none/placebo (Magpie Trial (2002):

-Apgar-score <7 at 5 minutes: RR=1.02 (0.85-1.22).

-Intubation: RR=1.01 (0.82-1.24)

-Admission to a special care baby unit: 1.01 (0.96-1.06) ]

Texas, USA (1995)

-Concealment of allocation unclear

-Unblinded

- Of the 1049 women allocated phenytoin, 17 also received MgSO4, and 139 did not receive it because of ’logistic’ problems (not clear if these women had MgSO4 instead

Nimodipine (2003):

-Concealment of allocation unclear.

-Unblinded trial, but primary outcome was described as “binary, objective, and not subject to measurement bias”

-100 (6%) women excluded from the analysis: 99 did not get allocated treatment. Recruitment stopped early following interim analysis.

Magpie Trial (2002)

High quality study.

Duley (2010) / diazepam

Design

Cochrane systematic review

Source of funding

Centre for Perinatal Health Services Research, Sydney, Australia; Department for International Development, UK; Medical Research Council, UK.

Search date

30 September 2010

Searched databases

Cochrane Pregnancy and Childbirth Group’s Trials Register: quarterly searches of the Cochrane Central Register of Controlled Trials (CENTRAL); 2. weekly searches of MEDLINE; 3. handsearches of 30 journals and the proceedings of major conferences; 4. weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.

Included study designs

All randomised comparisons of magnesium sulphate (intravenous or intramuscular administration for the maintenance regimen) with diazepam for women with eclampsia. Crossover trials were excluded.

Number of included studies

7 (Bangladesh, 1998; Collab Trial 1995; India 2001; Malaysia 1994; Nigaria 2004; Zimbabwe 1990; Zimbabwe 1998)

Women with a clinical diagnosis of eclampsia at trial entry.

4 of the included studies reported relevant outcomes:

Collab Trial, 1995

910 women with eclampsia

-Diazepam: 10 mg iv bolus. Then infusion of 40 mg /500 ml for 24hr, rate titrated against conscious level. 20 mg/500 ml for a further 24 hr. For recurrent convulsions, 10 mg iv MgS04: either (a) 4/5 g iv over 5 min and 10 g im. Then 5 g im every 4 hr, for 24 hr. Or (b) 4/5 iv over 5 min, then infusion of 1 g/hr for 24 hr.

Zimbabwe, 1990

-51 women with antepartum eclampsia, >28 weeks’ gestation.

-Diazepam: 10 mg iv bolus. Then infusion of 80 mg/l for 24 hr, rate titrated against conscious level. 40 mg/l for a further 24 hr. For recurrent convulsions, 10 mg iv MgS04: 4 g iv over 3-5 min and 10 g im. Then 5 g im every 4 hr, until 24 hr after delivery. For recurrent convulsions, 2 g iv

Nigeria, 2004

-60 women with eclampsia, 25% delivered prior to entry.

-Diazepam: loading dose of 10 mg iv over 2 minutes administered and repeated when convulsion recurred. Then 10 mg iv every 6 hours to keep patient sedated but arousable for next 24 hours

Zimbabwe, 1998:

-69 women with eclampsia

- Diazepam: 10 mg iv bolus. Then infusion of 40 mg /500 ml for 24 hr, rate titrated against conscious level. 20 mg/500 ml for a further 24 hr. For recurrent convulsions, 10 mg iv MgS04: either (a) 4/5 g iv over 5 min and 10 g im. Then 5 g im every 4 hr, for 24 hr. Or (b) 4/5 iv over 5 min, then infusion of 1 g/hr for 24 hr. For both (a) and (b), if recurrent convulsions 2 g iv

Intervention:

magnesium sulphate, given either by the intramuscular or the intravenous route,

Control:

diazepam

Relevant outcomes:

Apgar-score <7 at 1 minute

Apgar-score <7 at 5 minutes

Intubation

Special care nursery

Collab Trial, 1995; Zimbabwe 1990:

Apgar-score of less than seven at one minute (two trials; 597 infants; RR 0.75, 95% CI 0.65 to 0.87) in favour of magnesium sulphate

Collab Trial, 1995; Zimbabwe 1990: Nigeria 2004:

Apgar-score less than seven at five minutes (three trials; 643 infants; RR 0.70, 95% CI 0.54 to 0.90) in favour of magnesium sulphate

Collab Trial, 1995; Zimbabwe 1990:

Intubation (two trials; 591 infants; RR 0.67, 95% CI 0.45 to 1.00), borderline significance, less intubation needed in the group receiving magnesium sulphate.

Collab Trial, 1995; Zimbabwe 1990; Zimbabwe 1998:

Length of stay in a special care baby unit of more than seven days was reduced for babies born to women allocated magnesium sulphate rather than diazepam, although confidence intervals are wide (three trials; 634 infants; RR 0.66, 95% CI 0.46 to 0.96).

Admission to a special care baby unit was not significantly different between the two groups (three trials; 634 infants; RR 0.92, 95% CI 0.79 to 1.06).

Collab Trial, 1995

Blinding of the 2 treatment regimens was not possible. Outcome assessment was by the attending clinician, but outcomes used were largely objective, reducing potential for bias

Zimbabwe, 1990

Blinding not mentioned. Blinding of the 2 treatment regimens would have been impossible.

Nigeria, 2004

-Unclear concealment of allocation

-Blinding not mentioned.

-There is a discrepancy in some denominators, as the numbers for ’postpartum eclampsia’ are not the same as randomised after delivery’

Zimbabwe, 1998:

Blinding not mentioned. Blinding of the 2 treatment regimens would have been impossible.

Duley (2010) / lytic cocktail

Design

Cochrane systematic review

Source of funding

UNDP/UNFPA/WHO/World Bank (HRP), Switzerland; Resource Centre for Randomised Trials, UK

Medical Research Council, UK; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO, Switzerland.

Search date

June 2010

Searched databases

Cochrane Pregnancy and Childbirth Group’s Trials Register by contacting the Trials Search Coordinator (July 2010). The Cochrane Pregnancy and Childbirth Group’s Trials Register is maintained by the Trials Search Coordinator and contains trials identified from: 1. quarterly searches of the Cochrane Central Register of Controlled Trials (CENTRAL); 2. weekly searches of MEDLINE; 3. handsearches of 30 journals and the proceedings of major conferences; 4. weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.

Included study designs

Any randomised comparison of magnesium sulphate (intravenous or intramuscular administration for the maintenance regimen) with lytic cocktail for women with eclampsia. We included all routes of administration, as well as any combination of drugs known as ’lytic cocktail’, regardless of the constituents or of how they were administered. Crossover trials were excluded.

Number of included studies

3

Women with a clinical diagnosis of eclampsia at randomisation irrespective of whether they were before or after delivery, had a singleton or multiple pregnancy, or whether an anticonvulsant had been given before trial entry.

Intervention:

Magnesium sulphate

Control:

Lyric cocktail

Relevant outcomes;

Apgar-score at five minutes: low (less than seven), very low (less than four), or lowest reported.

-endotracheal intubation.

-In a special care nursery for more than seven days.

No trials were included reporting Apgar-scores, endotracheal intubation, or in a special care nursery for more than seven days (or any other relevant outcomes).

Duley (2010) / phenytoin

Design

Cochrane systematic review

Source of funding

Centre for Perinatal Health Services Research, University of Sydney, Australia; Department for International Development, UK; Medical Research Council, UK; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization, Switzerland.

Search date

30 April 2010

Searched databases

Cochrane Pregnancy and Childbirth Group’s Trials Register

Included study designs

All adequately randomised trials comparing magnesium sulphate with phenytoin for treatment of women with eclampsia. Crossover trials were excluded.

Number of included studies

7

Women with eclampsia.

Intervention:

Magnesium sulphate

Control:

Phenytoin

Relevant outcomes:

Apgar-score at five minutes: low (less than seven), very low less than four), or lowest reported

In a special care nursery for more than seven days.

1 trial included: Collab trial, 1995: see diazepam. No new trials included.

Study

Design, follow-up, setting

Patients

Method

Outcomes

Results

Results critical appraisal

Abdul (2013)

Design

Randomized controlled trial

Setting

The Federal Medical Centre Azare is a public referral centre serving the northern part of Bauchi state and the neighbouring Yobe State, in north-eastern Nigeria.

72 patients were recruited into the study. Of these, 39 were randomized into low-dose magnesium sulphate group while 33 were in the standard regimen group.

The mean gestational age of the patients was 35.5 ± 2.7 weeks.

32 patients (44%) were admitted in labour (intrapartum eclampsia) while 26 and 15% of

the patients were antepartum and postpartum eclampsia,

respectively.

Patients randomized into the standard dose regimen received 14 g loading dose of magnesuim sulphate (4 g of 20% iv + 10 g im) followed by im maintenance dose of 5 g four hourly for 24 h post-delivery or post last fit if further convulsions occurred within 24 h of delivery. Those in the low-dose group received 9 g loading dose (4 g of 20% iv and 5 g im) then im maintenance of 2.5 g four hourly for 24 h post-delivery or post last fit whichever was earlier.

In both study groups, 2 g iv of magnesium sulphate is given for breakthrough convulsions and 10 ml of 10% calcium gluconate (slowly iv) was administered in the event of toxicity.

Mean Apgar-score

Mean Apgar-score (5 min):

5.2 ± 3.3 versus 6.7 ± 2.4 (p=0.186)

-small sample size

-not blinded

Colón (2016)

Design

Randomized double-blinded trial

Setting

Northern California tertiary referral centers for high-risk

Pregnancies

Eligible patients were pregnant women between 24 and 34 weeks of gestation presenting to labor and delivery with

vaginal bleeding and uterine contractions or irritability admitted

with a clinical diagnosis of nonsevere placental abruption.

Exclusion criteria were placenta previa, progressive cervical change consistent with preterm labor, preterm premature rupture of the membranes, nonreassuring fetal heart rate pattern, severe vaginal bleeding needing immediate delivery, maternal coagulopathy, known renal disease, myasthenia gravis, major congenital anomalies, and chorioamnionitis.

A total of 30 women were enrolled in the study: 15 (50%) women received magnesium sulfate tocolysis and 15 (50%) received intravenous saline.

Gestational age at randomization (wk) 30 (25–31) versus 30 (28–32)

Gestational age at delivery (wk) 37.5 (32.5–39) versus 36 (32–38)

Apgar-score

NICU admission

1-minute Apgar 8 (8–9) versus 8 (8–9) 0.97

5-minute Apgar 9 (9–9)

versus 9 (9–9) 0.95

6 (47.9) versus 6 (35.3)

(p=0.72)

Small sample size

MgSO4 compared to placebo for women considered at risk of preterm birth

Patient or population: women considered at risk of preterm birth

Settings:
Intervention: MgSO4

Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

MgSO4

Apgar-score<7 at 5 minutes

Study population

RR 0.51
(0.05 to 5.46)

135
(1 study)

⊕⊕⊝⊝
low^1,2,3

29 per 1000

15 per 1000
(1 to 161)

Moderate

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio.

GRADE Working Group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low quality: We are very uncertain about the estimate.

¹ With no access to a trial protocol, it was not possible to determine if outcome data for all pre-specified outcomes were reported

² 1 study only.

³ Total number of events is less than 300 and 95% CI around the pooled estimate of effect includes both 1) no effect and 2) appreciable benefit or appreciable harm.

MgSO4 compared to different dosage MgSO4 for women with (pre-)eclampsia

Patient or population: women with (pre-)eclampsia

Settings:

Intervention: MgSO4

Comparison: different dosage MgSO4

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Different dosage MgSO4

MgSO4

Hypotonia

Study population

RR 0.13
(0.02 to 0.98)

35
(1 study)

⊕⊕⊝⊝
low^1,2,3

412 per 1000

54 per 1000
(8 to 404)

Moderate

Admission to special care unit

Study population

RR 2.36
(0.53 to 10.58)

0
(1 study)

⊕⊝⊝⊝
very low^1,2,4,5

See comment

See comment

Moderate

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low quality: We are very uncertain about the estimate.

¹ Concealment of allocation and blinding unclear.

² 1 study only.

³ The gestational age of the children was not mentioned. It may have been very preterms.

⁴ No explanation was provided

⁵ Total number of events is less than 300 and 95% CI around the pooled estimate of effect includes both 1) no effect and 2) appreciable benefit or appreciable harm.

MgSO4 compared to phenytoin for women with pre-eclampsia

Patient or population: women with pre-eclampsia

Settings:

Intervention: MgSO4

Comparison: phenytoin

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Phenytoin

MgSO4

Apgar-score at 5 minutes

Study population

RR 0.58
(0.26 to 1.3)

2141
(1 study)

⊕⊕⊝⊝
low^1,2

15 per 1000

9 per 1000
(4 to 19)

Moderate

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low quality: We are very uncertain about the estimate.

¹ Concealment of allocation and blinding unclear.

² 1 study only.

MgSO4 compared to Nimodipine for women with pre-eclampsia

Patient or population: women with pre-eclampsia

Settings:

Intervention: MgSO4

Comparison: Nimodipine

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Nimodipine

MgSO4

Hypotonia

Study population

RR 1.78
(0.91 to 3.46)

1564
(1 study)

⊕⊝⊝⊝
very low^1,2,3

17 per 1000

30 per 1000
(15 to 59)

Moderate

Hypotension

Study population

RR 0.32
(0.06 to 1.58)

1564
(1 study)

⊕⊕⊝⊝
low^1,2,3

8 per 1000

3 per 1000
(0 to 12)

Moderate

Intubation

Study population

RR 1.37
(0.91 to 2.05)

1564
(1 study)

⊕⊕⊝⊝
low^1,2,3

50 per 1000

68 per 1000
(45 to 102)

Moderate

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low quality: We are very uncertain about the estimate.

¹ Concealment of allocation and blinding unclear.

² 1 study only.

³ Total number of events <300 and 95% CI around the pooled estimate of effect includes both 1) no effect and 2) appreciable benefit or appreciable harm

MgSO4 compared to no treatment / placebo for women with pre-eclampsia

Patient or population: women with pre-eclampsi

Intervention: MgSO

Comparison: no treatment / placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

No treatment / placebo

MgSO4

Apgar-score<7 at 5 minutes

Study population

RR 1.02
(0.85 to 1.22)

8260
(1 study)

⊕⊕⊕⊕
high

55 per 1000

57 per 1000
(47 to 68)

Moderate

Intubation

Study population

RR 1.01
(0.82 to 1.24)

8260
(1 study)

⊕⊕⊕⊕
high

42 per 1000

42 per 1000
(34 to 52)

Moderate

Admission to special care baby unit

Study population

RR 1.01
(0.96 to 1.06)

8260
(1 study)

⊕⊕⊕⊕
high

388 per 1000

392 per 1000
(373 to 412)

Moderate

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low quality: We are very uncertain about the estimate.

Low dosis MgSO4 compared to Standard dosis MgSO4 for

Intervention: Low dosis MgSO4

Comparison: Standard dosis MgSO4

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Standard dosis MgSO4

Low dosis MgSO4

MD Apgar-score at 5 minutes

The mean md Apgar-score at 5 minutes in the intervention groups was
1.5 higher
(0.12 to 2.88 higher)

72
(1 study)

⊕⊕⊝⊝
low^1,2,3

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval;

GRADE Working Group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low quality: We are very uncertain about the estimate.

¹ No blinding.

² 1 study only.

³ Small sample size, large CI.

MgSO4 compared to IV normal saline for Women with nonsevere placental abruption

Patient or population: Women with nonsevere placental abruption

Intervention: MgSO4

Comparison: IV normal saline

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

IV normal saline

MgSO4

MD Apgar-score at 5 minutes

The mean md Apgar-score at 5 minutes in the intervention groups was
0 higher
(0.37 lower to 0.37 higher)

30
(1 study)

⊕⊕⊕⊝
moderate^1,2

NICU admission

Study population

RR 0.82
(0.34 to 1.99)

31
(1 study)

⊕⊕⊕⊝
moderate^1,2

429 per 1000

351 per 1000
(146 to 853)

Moderate

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low quality: We are very uncertain about the estimate.

¹ 1 study only.

² Small sample size (n=30).

MgSO4 compared to diazepam for women with pre-eclampsia

Patient or population: women with pre-eclampsia

Intervention: MgSO4

Comparison: diazepam

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Diazepam

MgSO4

Apgar-score <7 at 1 minute

Study population

RR 0.75
(0.65 to 0.87)

597
(2 studies)

⊕⊕⊝⊝
low^1,2

90 per 1000

68 per 1000
(59 to 79)

Moderate

Apgar-score <7 at 5 minutes

Study population

RR 0.70
(0.54 to 0.90)

643
(3 studies)

⊕⊕⊝⊝
low^1,2

332 per 1000

233 per 1000
(179 to 299)

Moderate

Intubation

Study population

RR 0.67
(0.45 to 1.00)

591
(2 studies)

⊕⊕⊝⊝
low^1,2

177 per 1000

119 per 1000
(80 to 177)

Moderate

Special care baby unit >7 days

Study population

RR 0.67
(0.45 to 1.00)

585
(3 studies)

⊕⊕⊝⊝
low^1,2

181 per 1000

121 per 1000
(81 to 181)

Moderate

Admission to special care baby unit

Study population

RR 0.92
(0.79 to 1.06)

634
(3 studies)

⊕⊕⊝⊝
low^1,2

548 per 1000

504 per 1000
(433 to 580)

Moderate

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low quality: We are very uncertain about the estimate.

¹ Blinding unclear, blinding of regimens not possible.

² Partly very preterm infants included.

Author(s): LV

Date: 2016-08-16

Question: Should MgSO4 vs placebo be used in women considered at risk of preterm birth?

Bibliography: Wiltlin (1997) in Nguyen et al. (2013)

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

MgSO4

Placebo

Relative
(95% CI)

Absolute

Apgar-score<7 at 5 minutes

1

randomised trials

serious¹

no serious inconsistency²

no serious indirectness

serious³

none

1/67
(1.5%)

2/68
(2.9%)

RR 0.51 (0.05 to 5.46)

14 fewer per 1000 (from 28 fewer to 131 more)


LOW

IMPORTANT

0%

-

Author(s): LV

Date: 2016-08-16

Question: Should MgSO4 vs different dosage MgSO4 be used in women with (pre-)eclampsia?

Bibliography: Shilva (2007) in Duley (2011)

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

MgSO4

Different dosage MgSO4

Relative
(95% CI)

Absolute

Hypotonia

1

randomised trials

serious¹

no serious inconsistency²

serious³

no serious imprecision

none

1/18
(5.6%)

7/17
(41.2%)

RR 0.13 (0.02 to 0.98)

358 fewer per 1000 (from 8 fewer to 404 fewer)


LOW

IMPORTANT

0%

-

Admission to special care unit

1

randomised trials

serious¹

no serious inconsistency²

serious⁴

serious⁵

none

-

-

RR 2.36 (0.53 to 10.58)

-


VERY LOW

IMPORTANT

0%

-

Author(s): LV

Date: 2016-08-16

Question: Should MgSO4 vs phenytoin be used in women with pre-eclampsia?

Bibliography: Texas 1995 in Duley (2010)

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

MgSO4

Phenytoin

Relative
(95% CI)

Absolute

Apgar-score at 5 minutes

1

randomised trials

very serious¹

no serious inconsistency²

no serious indirectness

no serious imprecision

none

9/1055
(0.85%)

16/1086
(1.5%)

RR 0.58 (0.26 to 1.3)

6 fewer per 1000 (from 11 fewer to 4 more)


LOW

IMPORTANT

0%

-

Author(s): LV

Date: 2016-08-16

Question: Should MgSO4 vs Nimodipine be used in women with pre-eclampsia?

Bibliography: Nimodipine 2003 in Duley (20110)

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

MgSO4

Nimodipine

Relative
(95% CI)

Absolute

Hypotonia

1

randomised trials

very serious¹

no serious inconsistency²

no serious indirectness

serious³

none

24/797
(3%)

13/767
(1.7%)

RR 1.78 (0.91 to 3.46)

13 more per 1000 (from 2 fewer to 42 more)


VERY LOW

IMPORTANT

0%

-

Hypotension

1

randomised trials

serious¹

no serious inconsistency²

no serious indirectness

serious³

none

2/797
(0.25%)

6/767
(0.78%)

RR 0.32 (0.06 to 1.58)

5 fewer per 1000 (from 7 fewer to 5 more)


LOW

CRITICAL

0%

-

Intubation

1

randomised trials

serious¹

no serious inconsistency²

no serious indirectness

serious³

none

54/797
(6.8%)

38/767
(5%)

RR 1.37 (0.91 to 2.05)

18 more per 1000 (from 4 fewer to 52 more)


LOW

IMPORTANT

0%

-

Author(s): LV

Date: 2016-08-16

Question: Should MgSO4 vs no treatment / placebo be used in women with pre-eclampsia?

Bibliography: Magpie Trial 2002 in Duley 2010

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

MgSO4

No treatment / placebo

Relative
(95% CI)

Absolute

Apgar-score<7 at 5 minutes

1

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

no serious imprecision

none

235/4162
(5.6%)

227/4098
(5.5%)

RR 1.02 (0.85 to 1.22)

1 more per 1000 (from 8 fewer to 12 more)


HIGH

IMPORTANT

0%

-

Intubation

1

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

no serious imprecision

none

175/4162
(4.2%)

171/4098
(4.2%)

RR 1.01 (0.82 to 1.24)

0 more per 1000 (from 8 fewer to 10 more)


HIGH

IMPORTANT

0%

-

Admission to special care baby unit

1

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

no serious imprecision

none

1629/4162
(39.1%)

1591/4098
(38.8%)

RR 1.01 (0.96 to 1.06)

4 more per 1000 (from 16 fewer to 23 more)


HIGH

IMPORTANT

0%

-

Author(s): LV

Date: 2016-08-16

Question: Should Low dosis MgSO4 vs Standard dosis MgSO4 be used in ?

Bibliography: Abdul et al. (2013)

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Low dosis MgSO4

Standard dosis MgSO4

Relative
(95% CI)

Absolute

MD Apgar-score at 5 minutes (Better indicated by lower values)

1

randomised trials

serious¹

no serious inconsistency²

no serious indirectness

serious³

none

39

33

-

MD 1.5 higher (0.12 to 2.88 higher)


LOW

IMPORTANT

Author(s): LV

Date: 2016-08-16

Question: Should MgSO4 vs IV normal saline be used in Women with nonsevere placental abruption?

Bibliography: Colón 2016

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

MgSO4

IV normal saline

Relative
(95% CI)

Absolute

MD Apgar-score at 5 minutes (Better indicated by lower values)

1

randomised trials

no serious risk of bias

no serious inconsistency¹

no serious indirectness

serious²

none

15

15

-

MD 0 higher (0.37 lower to 0.37 higher)


MODERATE

IMPORTANT

NICU admission

1

randomised trials

no serious risk of bias

no serious inconsistency¹

no serious indirectness

serious²

none

6/17
(35.3%)

6/14
(42.9%)

RR 0.82 (0.34 to 1.99)

77 fewer per 1000 (from 283 fewer to 424 more)


MODERATE

IMPORTANT

0%

-

Author(s): LV

Date: 2017-01-26

Question: Should MgSO4 vs diazepam be used in women with pre-eclampsia?

Settings:
Bibliography: Duley (2010)

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

MgSO4

Diazepam

Relative
(95% CI)

Absolute

Apgar-score <7 at 1 minute

2

randomised trials

serious¹

no serious inconsistency

serious²

no serious imprecision

none

150/309
(48.5%)

26/288
(9%)

RR 0.75 (0.65 to 0.87)

23 fewer per 1000 (from 12 fewer to 32 fewer)


LOW

IMPORTANT

0%

-

Apgar-score <7 at 5 minutes

3

randomised trials

serious¹

no serious inconsistency

serious²

no serious imprecision

none

76/330
(23%)

104/313
(33.2%)

RR 0.70 (0.54 to 0.90)

100 fewer per 1000 (from 33 fewer to 153 fewer)


LOW

IMPORTANT

0%

-

Intubation

2

randomised trials

serious¹

no serious inconsistency

serious²

no serious imprecision

none

36/303
(11.9%)

51/288
(17.7%)

RR 0.67 (0.45 to 1.00)

58 fewer per 1000 (from 97 fewer to 0 more)


LOW

IMPORTANT

0%

-

Special care baby unit >7 days

3

randomised trials

serious¹

no serious inconsistency

serious²

no serious imprecision

none

36/303
(11.9%)

51/282
(18.1%)

RR 0.67 (0.45 to 1.00)

60 fewer per 1000 (from 99 fewer to 0 more)


LOW

IMPORTANT

0%

-

Admission to special care baby unit

3

randomised trials

serious¹

no serious inconsistency

serious²

no serious imprecision

none

166/329
(50.5%)

167/305
(54.8%)

RR 0.92 (0.79 to 1.06)

44 fewer per 1000 (from 115 fewer to 33 more)


LOW

IMPORTANT

0%

-