Department of Global Health, School of Public Health, University of Washington, Seattle, USA.
Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique.
Malar J. 2020 Apr 8;19(1):144. doi: 10.1186/s12936-020-03210-y.
While there is increasing evidence on the safety of artemisinin-based combination therapy (ACT) for the case management of malaria in early pregnancy, little is known about the association between exposure to ACT during the first trimester and the effect on fetal growth.
Data were analysed from prospective studies of pregnant women enrolled in Mozambique, Burkina Faso and Kenya designed to determine the association between anti-malarial drug exposure in the first trimester and pregnancy outcomes, including low birth weight (LBW) and small for gestational age (SGA). Exposure to anti-malarial drugs was ascertained retrospectively by record linkage using a combination of data collected from antenatal and adult outpatient clinic registries, prescription records and self-reported medication usage by the women. Site-level data synthesis (fixed effects and random effects) was conducted as well as individual-level analysis (fixed effects by site).
Overall, 1915 newborns were included with 92 and 26 exposed to ACT (artemether-lumefantrine) and quinine, respectively. In Burkina Faso, Mozambique and Kenya at recruitment, the mean age (standard deviation) was 27.1 (6.6), 24.2 (6.2) and 25.7 (6.5) years, and the mean gestational age was 24.0 (6.2), 21.2 (5.7) and 17.9 (10.2) weeks, respectively. The LBW prevalence among newborns born to women exposed to ACT and quinine (QNN) during the first trimester was 10/92 (10.9%) and 7/26 (26.9%), respectively, compared to 9.5% (171/1797) among women unexposed to any anti-malarials during pregnancy. Compared to those unexposed to anti-malarials, ACT and QNN exposed women had the pooled LBW prevalence ratio (PR) of 1.13 (95% confidence interval (CI) 0.62-2.05, p-value 0.700) and 2.03 (95% CI 1.09-3.78, p-value 0.027), respectively. Compared to those unexposed to anti-malarials ACT and QNN-exposed women had the pooled SGA PR of 0.85 (95% CI 0.50-1.44, p-value 0.543) and 1.41 (95% CI 0.71-2.77, p-value 0.322), respectively. Whereas compared to ACT-exposed, the QNN-exposed had a PR of 2.14 (95% CI 0.78-5.89, p-value 0.142) for LBW and 8.60 (95% CI 1.29-57.6, p-value 0.027) for SGA. The level of between sites heterogeneity was moderate to high.
ACT exposure during the first trimester was not associated with an increased occurrence of LBW or SGA. However, the data suggest a higher prevalence of LBW and SGA for children born to QNN-exposed pregnancies. The findings support the use of ACT (artemether-lumefantrine) for the treatment of uncomplicated malaria during the first trimester of pregnancy.
虽然越来越多的证据表明青蒿素类复方疗法（ACT）在早孕时用于疟疾病例管理是安全的，但对于妊娠早期接触 ACT 与胎儿生长的影响之间的关联知之甚少。
对在莫桑比克、布基纳法索和肯尼亚进行的前瞻性孕妇研究中的数据进行了分析，旨在确定妊娠早期抗疟药物暴露与妊娠结局（包括低出生体重（LBW）和小于胎龄儿（SGA））之间的关联。通过结合从产前和成人门诊登记册、处方记录和妇女自我报告的药物使用情况中收集的数据进行抗疟药物暴露的回顾性记录链接来确定。进行了基于站点的数据综合（固定效应和随机效应）和个体水平分析（按站点固定效应）。
共有 1915 名新生儿入组，其中 92 名和 26 名分别接触了 ACT（青蒿琥酯-咯萘啶）和奎宁。在布基纳法索、莫桑比克和肯尼亚招募时，平均年龄（标准差）分别为 27.1（6.6）、24.2（6.2）和 25.7（6.5）岁，平均孕龄分别为 24.0（6.2）、21.2（5.7）和 17.9（10.2）周。在妊娠期间未接触任何抗疟药物的女性中，出生的新生儿 LBW 患病率为 9.5%（171/1797），而 ACT 和 QNN 暴露的女性 LBW 患病率分别为 10.9%（92/92）和 26.9%（26/26）。与未接触抗疟药物的女性相比，ACT 和 QNN 暴露的女性 LBW 患病率比值（PR）分别为 1.13（95%置信区间（CI）0.62-2.05，p 值 0.700）和 2.03（95% CI 1.09-3.78，p 值 0.027）。与未接触抗疟药物的女性相比，ACT 和 QNN 暴露的女性 SGA 的 PR 分别为 0.85（95% CI 0.50-1.44，p 值 0.543）和 1.41（95% CI 0.71-2.77，p 值 0.322）。与 ACT 暴露相比，QNN 暴露的女性 LBW 的 PR 为 2.14（95% CI 0.78-5.89，p 值 0.142），SGA 的 PR 为 8.60（95% CI 1.29-57.6，p 值 0.027）。各站点间的异质性水平为中度至高度。
妊娠早期接触 ACT 与 LBW 或 SGA 的发生率增加无关。然而，数据表明，QNN 暴露妊娠的新生儿 LBW 和 SGA 的发生率更高。这些发现支持在妊娠早期使用 ACT（青蒿琥酯-咯萘啶）治疗无并发症疟疾。
