背景:妊娠早期的疟疾与不良妊娠结局有关。青蒿素为基础的联合疗法(ACTs)是一种非常有效的,一线治疗无并发症的恶性疟原虫疟疾,除了在怀孕的头三个月,由于担心青蒿素的潜在胚胎毒性,建议使用奎宁和克林霉素。我们比较了以青蒿素为基础的治疗(ABT)和非ABTs在妊娠早期的不良妊娠结局。
方法:对于本系统评价和个体患者数据(IPD)荟萃分析,我们搜索了MEDLINE,Embase,和2015年11月1日至2021年12月21日发表的前瞻性队列研究的妊娠疟疾图书馆,其中包含妊娠早期暴露于ABT和非ABT的妊娠结局数据.这项搜索的结果被添加到先前的系统审查的结果中,其中包括直到11月为止出版的出版物,2015.我们包括在已知妊娠结局之前登记的妊娠。我们排除了缺少估计胎龄或暴露信息的妊娠,多胎妊娠,如果胎儿在抗疟治疗前被证实不能存活。主要终点是不良妊娠结局,定义为流产的复合物,死产,或主要的先天性异常。通过使用共享脆弱的Cox模型进行了一个阶段的IPD荟萃分析。这项研究在PROSPERO注册,编号CRD42015032371。
结果:我们确定了7项符合条件的研究,包括12个队列。所有12个队列都贡献了IPD,包括34178次怀孕,737例确认妊娠早期暴露于ABTs,1076例确认妊娠早期暴露于非ABTs。在妊娠早期,736例ABT暴露妊娠中有42例(5·7%)出现不良妊娠结局,而1074例非ABT暴露妊娠中有96例(8·9%)出现不良妊娠结局(调整后风险比[aHR]0·71,95%CI0·49-1·03)。对于流产的各个组成部分也看到了类似的结果(AHR=0·74,0·47-1·17),死产(AHR=0·71,0·32-1·57),和主要的先天性异常(aHR=0·60,0·13-2·87)。在妊娠的前三个月,蒿甲醚-本美特林的不良妊娠结局风险低于口服奎宁(524中的25[4·8%]对915中的84[9·2%];aHR0·58,0·36-0·92)。
结论:我们没有发现基于流产风险的胚胎毒性或致畸性证据,死产,或在怀孕的前三个月与ABT相关的主要先天性异常。鉴于与奎宁相比,蒿甲醚-本特林治疗的不良妊娠结局较少,并且由于已知ACTs具有优越的耐受性和抗疟效力,在妊娠早期,应将蒿甲醚-lumefantrine视为无并发症的恶性疟原虫疟疾的首选治疗方法。如果蒿甲醚-lumefantrine不可用,其他ACTs(青蒿琥酯-磺胺多辛-乙胺嘧啶除外)应优于奎宁。继续积极的药物警戒是必要的。
背景:疟疾药物风险,WHO,以及由比尔和梅林达·盖茨基金会资助的全球抗疟网络。
Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy.
For this systematic
review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic
review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371.
We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92).
We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted.
Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.