Morehouse School of Medicine, Atlanta, GA, USA.
Malaria Branch, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
J Travel Med. 2019 Jun 1;26(4). doi: 10.1093/jtm/tay138.
Malaria during pregnancy increases the risk of maternal and foetal complications. There are very limited options for prophylaxis in pregnant travellers. Atovaquone-Proguanil (AP or Malarone®) is an effective and well-tolerated antimalarial medication, but is not recommended for use in pregnancy due to limited data on safety. Passively reported adverse event data may provide additional information on the safety of AP during pregnancy.
We analysed adverse event data on pregnancy and birth outcomes following accidental exposures to AP during pregnancy, which were passively reported to GlaxoSmithKline LLC (GSK) between 13 May 1997 and 15 August 2017. Birth outcomes of interest included live birth, miscarriage, and stillbirth. Adverse outcomes of interest were defined as any of the following: small for gestational age (SGA), low birth weight (LBW, <2500 gm), congenital anomalies, and a composite 'poor live birth outcome,' including preterm birth (PTB), LBW or SGA.
Among 198 women who received AP during pregnancy or breastfeeding, 96.5% occurred in women taking malaria prophylaxis, and 79.8% of exposures occurred in the first trimester. Among 195 with available birth outcome data, 18.5% resulted in miscarriage and 11.8% were elective terminations. Available adverse outcomes included SGA in 3.5% (3/85), LBW in 7.0% of infants (6/86), and the composite 'poor live birth outcome' in 13.7% (14/102). Congenital anomalies were reported in 30/124 (24.2%), with no specific pattern to suggest an effect related to AP.
These data provide a description of outcomes in the pregnancies reported to this dataset, and it should be noted that there is likely a bias towards reporting cases resulting in poor outcomes. While there was no specific signal to suggest a teratogenic effect of AP, AP data during pregnancy were too limited to determine AP's safety with confidence. As inadvertent exposures are not infrequent, better data are needed.
孕妇疟疾会增加母婴并发症的风险。孕妇旅行者的预防选择非常有限。阿托伐醌-磺胺多辛（AP 或科泰复®）是一种有效且耐受性良好的抗疟药物，但由于关于安全性的数据有限，不建议在怀孕期间使用。被动报告的不良事件数据可能提供有关 AP 怀孕期间安全性的额外信息。
我们分析了 1997 年 5 月 13 日至 2017 年 8 月 15 日期间 GSK 被动报告的怀孕期间意外接触 AP 后妊娠和分娩结局的不良事件数据。感兴趣的分娩结局包括活产、流产和死产。感兴趣的不良结局定义为以下任何一种：小于胎龄儿（SGA）、低出生体重（LBW，<2500 克）、先天畸形和“不良活产结局”的综合指标，包括早产（PTB）、LBW 或 SGA。
在 198 名怀孕期间或哺乳期接受 AP 的女性中，96.5%的女性正在服用疟疾预防药物，79.8%的暴露发生在孕早期。在 195 名有可用分娩结局数据的女性中，18.5%导致流产，11.8%为选择性终止妊娠。可用的不良结局包括 3.5%（3/85）的 SGA、7.0%的婴儿（6/86）的 LBW 和 13.7%（14/102）的“不良活产结局”的综合指标。报告了 30/124（24.2%）例先天畸形，没有特定模式表明与 AP 相关的效应。
这些数据提供了该数据集报告的妊娠结局描述，应该注意的是，报告导致不良结局的病例很可能存在偏见。虽然没有特定的信号表明 AP 有致畸作用，但 AP 在怀孕期间的数据太有限，无法确定其安全性。由于意外暴露并不罕见，因此需要更好的数据。
