Antihypertensive therapy for pregnancy hypertension and implications for fetal and neonatal heart rate monitoring: A systematic review of randomized trials and observational studies

IF 3.1 2区 医学 Q1 OBSTETRICS & GYNECOLOGY
Akalya Ganeshamoorthy, Omiete Fubara Duke, Hiten D. Mistry, Jeffrey N. Bone, Marianne Vidler, Edgardo Abalos, Katie Badawy, Asma Khalil, Peter von Dadelszen, Laura A. Magee
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Two reviewers independently assessed studies for inclusion and extracted data. Random effects meta-analysis was used to determine risk ratios (RRs) and 95% confidence intervals (CIs). 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引用次数: 0

Abstract

Introduction

Our objective was to evaluate whether antihypertensives affect fetal (FHR) or neonatal (neoHR) heart rate.

Material and methods

Electronic databases and clinical trial registers were searched to August 31, 2024. Eligibility included randomized (RCTs) or observational studies evaluating antihypertensives for pregnancy hypertension. Two reviewers independently assessed studies for inclusion and extracted data. Random effects meta-analysis was used to determine risk ratios (RRs) and 95% confidence intervals (CIs). Network meta-analysis was undertaken in a sensitivity analysis.

Results

Fifty-four RCTs (n = 5736 pregnancies) and 28 observational studies (n = 2 283 855) reported FHR (usually visually-interpreted) or neoHR (usually clinically-assessed).

FHR: Non-Severe Hypertension

Antihypertensives did not increase adverse FHR effects in RCTs of antihypertensives versus placebo/no therapy (RR = 1.08, 95% CI [0.62–1.89]; I2 = 43%; N = 10, n = 1567 pregnancies), antihypertensives versus methyldopa (RR = 1.40 [0.97–2.04]; I2 = 0%; N = 6, n = 515), or labetalol or pure beta-blockers versus other antihypertensives (RR = 1.70 [0.96–2.99]; I2 = 30%; N = 5, n = 501). In observational studies, adverse FHR effects were more common with: labetalol versus methyldopa, nifedipine or Chinese herbal medication (RR = 2.17 [1.15–4.08]; I2 = 47%; N = 4, n = 664), and bendroflumethiazide versus metoprolol (but not hydralazine), but 95% CIs were wide.

FHR: Severe Hypertension

Antihypertensives had no FHR effects in RCTs of antihypertensives versus either: placebo/no therapy (RR = 0.43 [0.16–1.20]; I2 = 0%; N = 3, n = 242), hydralazine (RR = 0.71 [0.29–1.72]; I2 = 13%; N = 11, n = 727), or CCBs (RR = 0.52 [0.12–2.16]; I2 = 0%, N = 9, n = 1675). In observational studies, there was no difference for labetalol versus other antihypertensives (RR = 0.34 [0.10–1.14], I2 = 87%; N = 4, n = 590), with heterogeneity due to a lower-quality labetalol versus hydralazine study. There were fewer adverse FHR effects for nifedipine versus hydralazine study (RR = 0.09 [0.01–0.68]; n = 49).

NeoHR: Severe Hypertension

RCTs of antihypertensives versus placebo/no therapy were not associated with adverse neoHR effects (RR = 1.26 [0.31–5.19]; I2 = 66%; N = 4, n = 406), with heterogeneity attributed to more neoHR effects with continuously monitored neoHR. Observational studies revealed no effect on neoHR of antihypertensives versus no therapy (RR = 1.06 [0.67–1.67]; I2 = 54%; N = 4, n = 37 359), but labetalol was associated with more adverse effects and metoprolol with fewer. In RCTs of antihypertensives versus other antihypertensives, there was no difference in adverse neoHR (RR = 3.0 [0.13–71.74]; N = 3, n = 162). Observational studies showed adverse neoHR effects in labetalol versus pure beta-blockers (RR = 1.99 [1.36–2.91]; I2 = 0%; N = 3, n = 16 204). No severe hypertension RCTs reported neoHR. Observational studies were limited. Network meta-analysis showed no significant relationships between antihypertensives and FHR or neoHR; 95% CIs were very wide.

Conclusions

Evidence is inadequate to draw reliable conclusions about the impact of antihypertensives on FHR or neoHR. At present, adverse FHR or neoHR effects should be attributed to evolving placental dysfunction.

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妊娠高血压的降压治疗及其对胎儿和新生儿心率监测的影响:随机试验和观察性研究的系统综述。
前言:我们的目的是评估抗高血压药物是否影响胎儿(FHR)或新生儿(neoHR)心率。材料和方法:检索电子数据库和临床试验注册库,截止到2024年8月31日。入选条件包括评估妊娠高血压降压药的随机(rct)或观察性研究。两名评论者独立评估研究纳入和提取数据。采用随机效应荟萃分析确定风险比(rr)和95%置信区间(ci)。敏感度分析采用网络元分析。结果:54项随机对照试验(n = 5736例妊娠)和28项观察性研究(n = 2 283 855例)报告了FHR(通常是目测解释)或新hr(通常是临床评估)。非重度高血压:抗高血压药与安慰剂/无治疗相比,抗高血压药没有增加不良的FHR效应(RR = 1.08, 95% CI [0.62-1.89]; I2 = 43%; N = 10, N = 1567例妊娠);抗高血压药与甲基多巴相比(RR = 1.40 [0.97-2.04]; I2 = 0%; N = 6, N = 515);拉贝他洛尔或纯β受体阻滞剂与其他抗高血压药相比(RR = 1.70 [0.96-2.99]; I2 = 30%; N = 5, N = 501)。在观察性研究中,拉贝洛尔与甲基多巴、硝苯地平或中草药的FHR不良反应更为常见(RR = 2.17 [1.15-4.08]; I2 = 47%; N = 4, N = 664),苯并氟甲肼与美托洛尔(但不包括肼嗪),但95% ci较宽。FHR:重度高血压:降压药与安慰剂/无治疗(RR = 0.43 [0.16-1.20]; I2 = 0%; N = 3, N = 242)、肼嗪(RR = 0.71 [0.29-1.72]; I2 = 13%; N = 11, N = 727)或CCBs (RR = 0.52 [0.12-2.16]; I2 = 0%, N = 9, N = 1675)相比无FHR作用。在观察性研究中,拉贝他洛尔与其他抗高血压药物没有差异(RR = 0.34 [0.10-1.14], I2 = 87%; N = 4, N = 590),异质性是由于拉贝他洛尔与肼嗪的研究质量较低。硝苯地平组与肼嗪组相比,FHR不良反应较少(RR = 0.09 [0.01-0.68]; n = 49)。新hr:严重高血压:降压与安慰剂/无治疗的随机对照试验与新hr不良反应无关(RR = 1.26 [0.31-5.19]; I2 = 66%; N = 4, N = 406),异质性归因于持续监测新hr的新hr效应更多。观察性研究显示,降压药与不治疗对新hr无影响(RR = 1.06 [0.67-1.67]; I2 = 54%; N = 4, N = 37359),但拉贝他洛尔的不良反应较多,美托洛尔的不良反应较少。在降压药与其他降压药的rct中,不良新hr无差异(RR = 3.0 [0.13-71.74]; N = 3, N = 162)。观察性研究显示,与纯β受体阻滞剂相比,拉贝他洛尔对新hr的不良影响(RR = 1.99 [1.36-2.91]; I2 = 0%; N = 3, N = 16 204)。没有严重高血压的随机对照试验报告新hr。观察性研究是有限的。网络荟萃分析显示抗高血压药物与FHR或neoHR之间无显著关系;95%的ci非常宽。结论:关于抗高血压药物对FHR或新hr的影响,证据不足,无法得出可靠的结论。目前,不良的FHR或新hr效应应归因于不断发展的胎盘功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.00
自引率
4.70%
发文量
180
审稿时长
3-6 weeks
期刊介绍: Published monthly, Acta Obstetricia et Gynecologica Scandinavica is an international journal dedicated to providing the very latest information on the results of both clinical, basic and translational research work related to all aspects of women’s health from around the globe. The journal regularly publishes commentaries, reviews, and original articles on a wide variety of topics including: gynecology, pregnancy, birth, female urology, gynecologic oncology, fertility and reproductive biology.
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