Oral Antihypertensives for Nonsevere Pregnancy Hypertension: Systematic Review, Network Meta- and Trial Sequential Analyses
Bibliographic record
Abstract
BACKGROUND: We aimed to address which antihypertensives are superior to placebo/no therapy or another antihypertensive for controlling nonsevere pregnancy hypertension and provide future sample size estimates for definitive evidence. METHODS: Randomized trials of antihypertensives for nonsevere pregnancy hypertension were identified from online electronic databases, to February 28, 2021 (registration URL: https://www.crd.york.ac.uk/PROSPERO/; unique identifier: CRD42020188725). Our outcomes were severe hypertension, proteinuria/preeclampsia, fetal/newborn death, small-for-gestational age infants, preterm birth, and admission to neonatal care. A Bayesian random-effects model generated estimates of direct and indirect treatment comparisons. Trial sequential analysis informed future trials needed. RESULTS: Of 1246 publications identified, 72 trials were included; 61 (6923 women) were informative. All commonly prescribed antihypertensives (labetalol, other β-blockers, methyldopa, calcium channel blockers, and mixed/multi-drug therapy) versus placebo/no therapy reduced the risk of severe hypertension by 30% to 70%. Labetalol decreased proteinuria/preeclampsia (odds ratio, 0.73 [95% credible interval, 0.54-0.99]) and fetal/newborn death (odds ratio, 0.54 [0.30-0.98]) compared with placebo/no therapy, and proteinuria/preeclampsia compared with methyldopa (odds ratio, 0.66 [0.44-0.99]) and calcium channel blockers (odds ratio, 0.63 [0.41-0.96]). No other differences were identified, but credible intervals were wide. Trial sequential analysis indicated that 2500 to 10 000 women/arm (severe hypertension or safety outcomes) to >15 000/arm (fetal/newborn death) would be required to provide definitive evidence. CONCLUSIONS: In summary, all commonly prescribed antihypertensives in pregnancy reduce the risk of severe hypertension, but labetalol may also decrease proteinuria/preeclampsia and fetal/newborn death. Evidence is lacking for many other safety outcomes. Prohibitive sample sizes are required for definitive evidence. Real-world data are needed to individualize care.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".