Table 1.
Summary of findings for medications to prevent preeclampsia
| Patient or population: Pregnant women at any gestational age at high risk of developing hypertensive disorders in pregnancy Settings: Hospital setting Intervention: Antiplatelet agents, anticoagulants, antioxidants, calcium, nitric oxide, and their combinations Comparator: Placebo or no treatment Outcome: Preeclampsia | ||||||||
|---|---|---|---|---|---|---|---|---|
| Total studies: 77 RCTs Total participants: 93,234 |
Direct estimates RR (95% CI) |
Certainty of evidence | Indirect estimates RR (95% CI) |
Certainty of evidence | Network estimates RR (95% CI) [95% PrI] |
Certainty of evidence | SUCRA | Comments |
| Antiplatelets + calcium (1 RCT; 334 participants) | 0.16 (0.03 to 0.75) |
⊕⊕⊝⊝ Lowa,b |
0.45 (0.05 to 4.06) |
⊕⊕⊕⊝ Moderateb |
0.19 (0.04 to 0.86) [0.04 to 1.01] |
⊕⊕⊝⊝ Lowa,b |
89.9% | There was no evidence of inconsistency for global inconsistency test (P = 0.459) and Dias’s inconsistency tests of the node splitting |
| Anticoagulants + antiplatelets + calcium (2 RCTs; 156 participants) | Not estimable | 0.24 (0.03 to 1.79) |
⊕⊝⊝⊝ Very lowc,d |
0.24 (0.03 to 1.79) [0.03 to 2.07] |
⊕⊝⊝⊝ Very lowc,d |
78.3% | ||
| Anticoagulants + antiplatelets (1 RCT; 20 participants) | 0.31 (0.07 to 1.27) |
⊕⊝⊝⊝ Very lowd,e |
0.46 (0.26 to 0.80) |
⊕⊕⊝⊝ Lowd |
0.43 (0.26 to 0.73) [0.19 to 1.01] |
⊕⊕⊝⊝ Lowd |
74.2% | |
| Calcium + antioxidants (1 RCT; 660 participants) | 0.39 (0.16 to 0.96) |
⊕⊕⊝⊝ Lowe |
0.93 (0.18 to 4.82) |
⊕⊕⊕⊝ Moderateb |
0.47 (0.20 to 1.06) [0.16 to 1.35] |
⊕⊕⊕⊝ Moderateb |
66.8% | |
| Calcium (13 RCTs; 26,021 participants) | 0.61 (0.46 to 0.80) |
⊕⊕⊕⊝ Moderatef |
0.69 (0.20 to 2.36) |
⊕⊕⊕⊝ Moderateb |
0.61 (0.47 to 0.80) [0.30 to 1.24] |
⊕⊕⊕⊝ Moderatef |
54.4% | |
| Anticoagulants (2 RCTs; 399 participants) | 0.70 (0.28 to 1.79) |
⊕⊕⊕⊝ Moderateb |
0.23 (0.02 to 2.28) |
⊕⊕⊕⊝ Moderateb |
0.60 (0.25 to 1.43) [0.20 to 1.80] |
⊕⊕⊕⊝ Moderateb |
51.7% | |
| Antiplatelets (31 RCTs; 41,953 participants) | 0.68 (0.57 to 0.82) |
⊕⊕⊝⊝ Lowa,f |
0.79 (0.27 to 2.33) |
⊕⊕⊕⊝ Moderateb |
0.69 (0.57 to 0.82) [0.35 to 1.35] |
⊕⊕⊕⊝ moderatef |
43.7% | |
| Antiplatelets + nitric oxide (No direct comparison) | Not estimable | Not estimable |
0.80 (0.31 to 2.05) [0.25 to 2.55] |
⊕⊕⊝⊝ lowd |
34.5% | |||
| Antioxidants (25 RCTs; 24,768 participants) | 0.76 (0.63 to 0.92) |
⊕⊕⊕⊝ Moderatef |
2.72 (0.27 to 27.33) |
⊕⊕⊕⊝ Moderateb |
0.77 (0.63 to 0.93) [0.39 to 1.52] |
⊕⊕⊕⊝ Moderatef |
32.3% | |
| Nitric oxide (1 RCT; 68 participants) | 1.35 (0.61 to 3.01) |
⊕⊝⊝⊝ Very lowd,e |
Not estimable |
1.35 (0.49 to 3.77) [0.39 to 4.65] |
⊕⊝⊝⊝ Very lowd,e |
11.4% | ||
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
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, PrI Prediction interval, RR Relative risk
aWe downgraded (1) level for serious limitations in study design due to most of the studies being at unclear risk of bias
bWe downgraded (1) level for serious imprecision due to wide confidence interval
cWe downgraded (1) level for serious intransitivity due to without closed loop of intervention
dWe downgraded (2) level for very serious imprecision due to wide confidence interval and small number of events and sample size
eWe downgraded (2) level for very serious limitations in study design due to most of the studies being at high risk of bias
fWe downgraded (1) level for serious publication bias due to asymmetry funnel plot and P-value of Egger’s test < 0.05