怀孕前三个月的疟疾与不良妊娠结局有关。基于青蒿素的联合疗法(ACTs)是对不复杂的恶性疟原虫疟疾的一种非常有效的一线治疗方法，但怀孕的前三个月除外，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。我们比较了妊娠前三个月以青蒿素为基础的治疗(ABT)与非ABT治疗后的不良妊娠结局。

我们确定了7项符合条件的研究，包括12个队列。所有12个队列均发生了IPD，包括34 178例妊娠，其中737例确诊在妊娠早期暴露于ABTs, 1,076例确诊在妊娠早期暴露于非ABTs。在妊娠早期，736例abt暴露孕妇中有42例(5.7%)发生不良妊娠结局，而1074例非abt暴露孕妇中有96例(8.9%)发生不良妊娠结局(校正风险比[aHR] 0.71, 95% CI 0.49 ~ 1.03)。自然流产(aHR= 0.74, 0.47 ~ 1.17)、死产(aHR= 0.71, 0.32 ~ 1.57)和主要先天畸形(aHR= 0.60, 0.13 ~ 2.87)的各构成部分也观察到类似的结果。在妊娠早期，蒿甲醚-苯芴醇组的不良妊娠结局风险低于口服奎宁组(25 [4.8%]/ 524 vs 84 [9.2%] / 915;aHR 0.58, 0.36 ~ 0.92)。

根据流产、死产或妊娠前3个月与ABT相关的严重先天性异常风险，我们未发现胚胎毒性或致畸性的证据。与奎宁相比，蒿甲醚-苯芴醇治疗的不良妊娠结局较少，而且已知ACTs的耐受性和抗疟效果较好。

Abstract

Background: 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.

Methods: 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.

Findings: 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).

Interpretation: 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.

文章连接：

www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01881-5/fulltext

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