WorldWide Antimalarial Resistance Network (WWARN), Oxford, UK.
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, UK.
Malar J. 2017 Dec 18;16(1):491. doi: 10.1186/s12936-017-2136-x.
Considering the uncertainty of safety of anti-malarial drugs in pregnancy, efficacy studies are one of the few sources of clinical safety data. Complete safety evaluation is not usually incorporated in efficacy studies due to financial and human resource constraints. This review reports the methods used for the assessment of safety of artemisinin-based and quinine-based treatments in efficacy studies in pregnancy.
Methodology of assessment and reporting of safety in efficacy studies of artemisinin-based and quinine-based treatment in pregnancy was reviewed using seven databases and two clinical trial registries. The protocol was registered to PROSPERO (CRD42017054808).
Of 48 eligible efficacy studies the method of estimation of gestational age was reported in only 32 studies (67%, 32/48) and ultrasound was used in 18 studies (38%, 18/48). Seventeen studies (35%, 17/48) reported parity, 9 (19%, 9/48) reported gravidity and 13 (27%, 13/48) reported both. Thirty-eight studies (79%, 38/48) followed participants through to pregnancy outcome. Fetal loss was assessed in 34 studies (89%, 34/38), but the definition of miscarriage and stillbirth were defined only in 11 (32%, 11/34) and 7 (21%, 7/34) studies, respectively. Preterm birth was assessed in 26 studies (68%, 26/38) but was defined in 16 studies (62%, 16/26). Newborn weight was assessed in 30 studies (79%, 30/38) and length in 10 studies (26%, 10/38). Assessment of birth weight took gestational age into account in four studies (13%, 4/30). Congenital abnormalities were reported in 32 studies (84%, 32/38). Other common risk factors for adverse pregnancy outcomes were not well-reported.
Incomplete reporting and varied methodological assessment of pregnancy outcomes in anti-malarial drug efficacy studies limits comparison across studies. A standard list of minimal necessary parameters to assess and report the safety component of efficacy studies of anti-malarials in pregnancy is proposed.
考虑到抗疟药物在妊娠期间的安全性不确定，疗效研究是临床安全性数据的少数来源之一。由于财力和人力资源的限制，通常不在疗效研究中纳入完整的安全性评估。本综述报告了评估妊娠期间基于青蒿素和奎宁的治疗方法疗效研究中安全性的方法。
使用七个数据库和两个临床试验注册中心，对妊娠期间基于青蒿素和奎宁的治疗方法疗效研究中安全性评估和报告方法进行了综述。该方案在 PROSPERO（CRD42017054808）中进行了注册。
在 48 项符合条件的疗效研究中，只有 32 项（67%，32/48）报告了估计胎龄的方法，18 项（38%，18/48）使用了超声。17 项（35%，17/48）报告了产次，9 项（19%，9/48）报告了孕次，13 项（27%，13/48）同时报告了产次和孕次。38 项（79%，38/48）研究随访至妊娠结局。34 项（89%，34/38）研究评估了胎儿丢失情况，但只有 11 项（32%，11/34）和 7 项（21%，7/34）研究分别定义了流产和死产的定义。26 项（68%，26/38）研究评估了早产情况，但只有 16 项（62%，16/26）研究对其进行了定义。30 项（79%，30/38）研究评估了新生儿体重，10 项（26%，10/38）研究评估了新生儿长度。4 项（13%，4/30）研究在评估出生体重时考虑了胎龄。32 项（84%，32/38）研究报告了先天性异常。其他不良妊娠结局的常见危险因素报告不充分。
抗疟药物疗效研究中妊娠结局的报告不完整且方法评估各异，限制了研究之间的比较。本研究提出了一个评估和报告妊娠期间抗疟药物疗效研究安全性的最低必要参数标准清单。
