BACKGROUND:

Malaria during pregnancy increases the risk of maternal and fetal complications. There are very limited options available for prophylaxis in pregnant travelers. 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.

METHODS:

We analyzed adverse event data on pregnancy and birth outcomes following accidental exposures to AP during pregnancy passively reported to GlaxoSmithKline LLC (GSK) between May 13, 1997 and August 15, 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.

RESULTS:

Among 198 women who received AP during pregnancy or breast-feeding, 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.

CONCLUSIONS:

These data provide a description of outcomes in the pregnancies reported to this data set, 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.

PMID: 30544231

DOI: 10.1093/jtm/tay138