Table 1.
Adverse effect estimates from randomised controlled trials (Comparison 1)
| Outcome or subgroup | Studies | Participants | Method (I 2 (%))* | RR (95% CI) |
|---|---|---|---|---|
|
Comparison 1: Magnesium sulphate versus placebo or no treatment | ||||
|
1.1 Death |
5 [17,19,20,23,25] |
14662 |
F (0) |
0.53 (0.26, 1.09) |
| 1.1.1 Treatment of pre-eclampsia/eclampsia |
2 [17,20] |
10795 |
F (0) |
0.53 (0.26, 1.09) |
| 1.1.2 Fetal neuroprotection |
3 [19,23,25] |
3867 |
F (NA) |
No deaths |
| 1.1.3 LD only |
1 [23] |
564 |
F (NA) |
No deaths |
| 1.1.4 LD and MD |
4 [17,19,20,25] |
14098 |
F (0) |
0.53 (0.26, 1.09) |
| 1.1.5 4 g IV LD and MD |
3 [17,19,20] |
11857 |
F (0) |
0.53 (0.26, 1.09) |
| 1.1.6 5–6 g IV LD and MD |
1 [25] |
2241 |
F (NA) |
No deaths |
| 1.1.7 1 g/hour IV MD |
3 [17,19,20] |
7264 |
F (0) |
0.41 (0.12, 1.43) |
| 1.1.8 2–3 g/hour IV MD |
1 [25] |
2241 |
F (NA) |
No deaths |
| 1.1.9 IM MD |
1 [20] |
4593 |
F (NA) |
0.61 (0.25, 1.48) |
|
1.2 Cardiac arrest |
4 [19,20,23,25] |
13977 |
F (NA) |
0.80 (0.21, 2.98) |
| 1.2.1 Treatment of pre-eclampsia/eclampsia |
1 [20] |
10110 |
F (NA) |
0.80 (0.21, 2.98) |
| 1.2.2 Fetal neuroprotection |
3 [19,23,25] |
3867 |
F (NA) |
No cardiac arrests |
| 1.2.3 LD only |
1 [23] |
564 |
F (NA) |
No cardiac arrests |
| 1.2.4 LD and MD |
3 [19,20,25] |
13413 |
F (NA) |
0.80 (0.21, 2.98) |
|
1.3 Respiratory arrest |
4 [19,20,23,25] |
13977 |
F (NA) |
2.50 (0.49, 12.88) |
| 1.3.1 Treatment of pre-eclampsia/eclampsia |
1 [20] |
10110 |
F (NA) |
2.50 (0.49, 12.88) |
| 1.3.2 Fetal neuroprotection |
3 [19,23,25] |
3867 |
F (NA) |
No respiratory arrests |
| 1.3.3 LD only |
1 [23] |
564 |
F (NA) |
No respiratory arrests |
| 1.3.4 LD and MD |
3 [19,20,25] |
13413 |
F (NA) |
2.50 (0.49, 12.88) |
|
1.4 Discontinuation due to adverse effects |
5 [18-20,25,26] |
13666 |
F (0) |
2.77 (2.32, 3.30) |
| 1.4.1 Treatment of pre-eclampsia/eclampsia |
2 [20,26] |
10245 |
F (0) |
2.69 (2.18, 3.31) |
| 1.4.2 Fetal neuroprotection |
2 [19,25] |
3265 |
F (0) |
2.81 (2.01, 3.93) |
| 1.4.3 Tocolysis |
1 [18] |
156 |
F (NA) |
17.88 (1.05, 304.57) |
| 1.4.4 LD and MD |
5 [18-20,25,26] |
13666 |
F (0) |
2.77 (2.32, 3.30) |
| 1.4.5 4 g IV LD and MD |
3 [18-20] |
11328 |
F (0) |
2.75 (2.28, 3.31) |
| 1.4.6 5–6 g IV LD and MD |
2 [25,26] |
2338 |
F (0) |
2.94 (1.69, 5.12) |
| 1.4.7 1 g/hour IV MD |
1 [19] |
1062 |
F (NA) |
2.74 (1.81, 4.15) |
| 1.4.8 2–3 g/hour IV MD |
3 [18,25,26] |
2494 |
F (0) |
3.38 (1.97, 5.78) |
|
1.5 Given calcium gluconate |
|
|
|
|
| 1.5.1 Treatment of pre-eclampsia/eclampsia |
2 [17,20] |
10795 |
F (0) |
1.35 (0.63, 2.88) |
| 1.5.2 4 g IV LD and MD |
2 [17,20] |
10795 |
F (0) |
1.35 (0.63, 2.88) |
|
1.6 Intensive care unit admission |
2 [19,20] |
11172 |
F (NA) |
0.97 (0.72, 1.30) |
| 1.6.1 Treatment of pre-eclampsia/eclampsia |
1 [20] |
10110 |
F (NA) |
0.97 (0.72, 1.30) |
| 1.6.2 Fetal neuroprotection |
1 [19] |
1062 |
F (NA) |
No admissions |
|
1.7 Any side effects |
4 [19,20,22,25] |
13322 |
R (98) |
4.62 (2.42, 8.83) |
| 1.7.1 Treatment of pre-eclampsia/eclampsia |
1 [20] |
9992 |
F (NA) |
5.26 (4.59, 6.03) |
| 1.7.2 Fetal neuroprotection |
2 [19,25] |
3265 |
R (98) |
3.82 (1.38, 10.59) |
| 1.7.3 Tocolysis |
1 [22] |
65 |
F (NA) |
26.71 (1.64, 435.03) |
| 1.7.4 LD and MD |
4 [19,20,22,25] |
13322 |
R (98) |
4.62 (2.42, 8.83) |
| 1.7.5 4 g IV LD and MD |
2 [19,20] |
11054 |
R (99) |
3.52 (1.49, 8.32) |
| 1.7.6 5–6 g IV LD and MD |
2 [22,25] |
2268 |
F (5) |
6.28 (5.36, 7.35) |
| 1.7.7 1 g /hour IV MD |
2 [19,20] |
6501 |
R (98) |
3.31 (1.59, 6.88) |
| 1.7.8 2–3 g/hour IV MD |
2 [22,25] |
2268 |
F (5) |
6.28 (5.36, 7.35) |
| 1.7.9 IM MD |
1 [20] |
4553 |
F (NA) |
5.84 (4.80, 7.09) |
|
1.8 Respiratory depression/other respiratory problems |
5[17-20,25] |
14098 |
F (29) |
1.41 (1.07, 1.86) |
| 1.8.1 Treatment of pre-eclampsia/eclampsia |
2 [17,20] |
10677 |
F (0) |
1.98 (1.24, 3.15) |
| 1.8.2 Fetal neuroprotection |
2 [19,25] |
3265 |
F (29) |
1.12 (0.79, 1.59) |
| 1.8.3 Tocolysis |
1 [18] |
156 |
F (NA) |
3.16 (0.13, 76.30) |
|
1.9 Absent or reduced tendon reflexes |
3 [17,20,23] |
11241 |
F (0) |
1.01 (0.71, 1.44) |
| 1.9.1 Treatment of pre-eclampsia/eclampsia |
2 [17,20] |
10677 |
F (0) |
1.00 (0.70, 1.42) |
| 1.9.2 Fetal neuroprotection |
1 [23] |
564 |
F (NA) |
1.94 (0.18, 21.32) |
|
1.10 Respiratory depression and absent reflexes |
|
|
|
|
| 1.10.1 Treatment of pre-eclampsia/eclampsia |
3 [17,20,21] |
10899 |
F (0) |
5.96 (0.72, 49.40) |
|
1.11 Hypotension |
3 [18,19,23] |
1782 |
F (0) |
1.52 (1.10, 2.11) |
| 1.11.1 Fetal neuroprotection |
2 [19,23] |
1626 |
F (0) |
1.51 (1.09, 2.09) |
| 1.11.2 Tocolysis |
1 [18] |
156 |
F (NA) |
3.16 (0.13, 76.30) |
|
1.12 Tachycardia |
|
|
|
|
| 1.12.1 Fetal neuroprotection |
1 [19] |
1062 |
F (NA) |
1.53 (1.03, 2.29) |
|
1.13 Flushing and/or warmth |
5 [19,20,23,25,26] |
13956 |
R (92) |
6.94 (4.19, 11.49) |
| 1.13.1 Treatment of pre-eclampsia/eclampsia |
2 [20,26] |
10127 |
R (91) |
6.39 (2.44, 16.74) |
| 1.13.2 Fetal neuroprotection |
3 [19,23,25] |
3829 |
R (94) |
7.55 (3.39, 16.85) |
|
1.14 Nausea and/or vomiting |
4 [19,20,23,25] |
13821 |
R (92) |
5.50 (2.29, 13.22) |
| 1.14.1 Treatment of pre-eclampsia/eclampsia |
1 [20] |
9992 |
F (NA) |
8.88 (5.46, 14.43) |
| 1.14.2 Fetal neuroprotection |
3 [19,23,25] |
3829 |
R (92) |
4.60 (1.54, 13.73) |
|
1.15 Muscle weakness |
3 [16,18,20] |
10212 |
F (0) |
15.81 (7.36, 33.96) |
| 1.15.1 Treatment of pre-eclampsia/eclampsia |
2 [16,20] |
10056 |
F (0) |
15.97 (7.23, 35.30) |
| 1.15.2 Tocolysis |
1 [18] |
156 |
F (NA) |
13.68 (0.78, 238.67) |
|
1.16 Drowsiness or confusion |
3 [19,20,26] |
11189 |
F (0) |
2.46 (1.83, 3.29) |
| 1.16.1 Treatment of pre-eclampsia/eclampsia |
2 [20,26] |
10127 |
F (0) |
2.26 (1.06, 4.85) |
| 1.16.2 Fetal neuroprotection |
1 [19] |
1062 |
F (NA) |
2.49 (1.82, 3.42) |
|
1.17 Headache |
2 [20,23] |
10556 |
F (0) |
2.21 (1.27, 3.86) |
| 1.17.1 Treatment of pre-eclampsia/eclampsia |
1 [20] |
9992 |
F (NA) |
2.12 (1.19, 3.76) |
| 1.17.2 Fetal neuroprotection |
1 [23] |
564 |
F (NA) |
3.89 (0.44, 34.57) |
|
1.18 Thirst or mouth dryness |
2 [19,20] |
11054 |
R (42) |
2.38 (1.59, 3.56) |
| 1.18.1 Treatment of pre-eclampsia/eclampsia |
1 [20] |
9992 |
F (NA) |
3.36 (1.72, 6.58) |
| 1.18.2 Fetal neuroprotection |
1 [19] |
1062 |
F (NA) |
2.11 (1.72, 2.59) |
|
1.19 Dizziness |
2 [19,20] |
11054 |
R (39) |
2.62 (1.63, 4.21) |
| 1.19.1 Treatment of pre-eclampsia/eclampsia |
1 [20] |
9992 |
F (NA) |
3.70 (1.84, 7.42) |
| 1.19.2 Fetal neuroprotection |
1 [19] |
1062 |
F (NA) |
2.21 (1.53, 3.19) |
|
1.20 Sweating |
|
|
|
|
| 1.20.1 Fetal neuroprotection |
2 [19,25] |
3265 |
R (95) |
6.37 (1.96, 20.65) |
|
1.21 Itching and/or tingling |
|
|
|
|
| 1.21.1 Treatment of pre-eclampsia/eclampsia |
1 [20] |
9992 |
F (NA) |
14.98 (1.98, 113.38) |
|
1.22 Blurred vision |
|
|
|
|
| 1.22.1 Fetal neuroprotection |
1 [19] |
1062 |
F (NA) |
2.34 (1.32, 4.14) |
|
1.23 Slurred speech |
|
|
|
|
| 1.23.1 Treatment of pre-eclampsia/eclampsia |
1 [26] |
135 |
F (NA) |
3.04 (0.13, 73.42) |
|
1.24 Problems at the IV site or arm discomfort |
3 [19,20,25] |
8704 |
R (92) |
6.34 (3.10, 12.98) |
| 1.24.1 Treatment of pre-eclampsia/eclampsia |
1 [20] |
5439 |
F (NA) |
3.05 (2.15, 4.32) |
| 1.24.2 Fetal neuroprotection |
2 [19,25] |
3265 |
F (NA) |
9.11 (7.18, 11.55) |
|
1.25 Problems at the IM site |
|
|
|
|
| 1.25.1 Treatment of pre-eclampsia/eclampsia |
1 [20] |
4553 |
F (NA) |
1.49 (1.25, 1.79) |
|
1.26 Caesarean section |
10 [16-21,23-26] |
14105 |
F (0) |
1.04 (1.00, 1.08) |
| 1.26.1 Treatment of pre-eclampsia/eclampsia |
6 [16,17,20-22,26] |
10096 |
F (0) |
1.05 (1.01, 1.10) |
| 1.26.2 Fetal neuroprotection |
3 [19,23,25] |
3853 |
F (19) |
1.00 (0.93, 1.08) |
| 1.26.3 Tocolysis |
1 [18] |
156 |
F (NA) |
0.90 (0.45, 1.82) |
|
1.27 Postpartum haemorrhage |
4 [19,20,23,26] |
10535 |
F (0) |
0.94 (0.87, 1.04) |
| 1.27.1 Treatment of pre-eclampsia/eclampsia |
2 [20,26] |
8909 |
R (43) |
1.31 (0.39, 4.41) |
| 1.27.2 Fetal neuroprotection |
2 [19,23] |
1626 |
F (0) |
0.84 (0.61, 1.15) |
|
1.28 Pulmonary oedema |
4 [20,21,24,25] |
12787 |
F (8) |
1.12 (0.72, 1.74) |
| 1.28.1 Treatment of pre-eclampsia/eclampsia |
3 [20,21,24] |
10560 |
F (0) |
0.95 (0.60, 1.57) |
| 1.28.2 Fetal neuroprotection | 1 [25] | 2227 | F (NA) | 2.80 (0.75, 10.53) |
I2 statistics is a test of heterogeneity; where I2 was > 30% summary estimates were calculated using random-effects meta-analysis; the bold effect estimates indicate statistical significance.
Abbreviations: CI confidence interval, F fixed-effect, g gram, IM intramuscular, IV intravenous, LD loading dose, MD maintenance dose, NA not applicable, R random-effects, RR risk ratio.