EVIDENCE-BASED ANSWER
Chloroquine and mefloquine have superior safety profiles in pregnancy, though all antimalarials are effective for prophylaxis. Antimalarials will decrease the severity of maternal malaria infection and malaria-associated anemia, while decreasing the incidence of low birth weight and perinatal death in women having their first or second baby (strength of recommendation [SOR]: A, based on systematic review of consistent, good-quality patient-oriented evidence).
You can determine malaria risk and sensitivity of Plasmodium species by country at wwwn.cdc.gov/travel/destinationlist.aspx.1 Urge women to delay travel until after pregnancy if possible2 (SOR: C, based on patient-oriented expert opinion).
Clinical commentary
Don’t forget to discuss mosquito netting and insect repellant
Meg Hayes, MD
Department of Family Medicine, Oregon Health and Science University, Portland
Adverse outcomes associated with malaria during pregnancy include restricted fetal growth, low birth weight, preterm delivery, congenital infection, spontaneous abortion, and perinatal death. You should counsel travelers to avoid travel to areas where malaria is endemic during pregnancy.
For those who are unable to avoid travel, or who reside in malaria-endemic areas during pregnancy, physicians should focus not only on chemoprophylaxis, but provide verbal and written counsel regarding malaria personal protection measures. Because mosquitoes usually feed at night, travelers should remain within screened areas after dusk, use permethrin-treated bed nets, wear protective clothing, and apply insect repellant. Advise patients who travel to malaria-endemic areas to quickly report febrile illnesses and to disclose their travel histories to healthcare providers.
Evidence summary
Malaria is a parasitic infection that causes significant morbidity and mortality worldwide, with more than 500 million people becoming severely ill every year.2 For pregnant women, malarial infection can be severe, with high fevers, chills, and anemia leading to increased risk of poor maternal and fetal outcomes—including death. Pregnant women are also more likely to become infected and to develop more severe disease—they attract twice as many mosquitoes as nonpregnant women and have a relative immuno-suppression.3
TABLE
Antimalarials for prophylaxis: Chloroquine, mefloquine are best choices during pregnancy
| DRUG | EFFICACY | SAFETY | PREGNANCY CLASS* | AVAILABILITY |
|---|---|---|---|---|
| Chloroquine | Good | Excellent | C | Worldwide |
| Chloroquine/proguanil | Good | Excellent | C | Worldwide |
| Mefloquine | Excellent | Good | C | Worldwide |
| Quinine | Excellent | Good | C† | Worldwide |
| Atovaquone/proguanil | Excellent | Good | C (poorly studied) | Worldwide |
| Artesunate | Excellent | Good | N/A | Asia, Africa, limited in UK, not in US |
| Primaquine | Good | Fair | C‡ | Worldwide |
| Doxycycline | Excellent | Fair | D (teratogenic) | Worldwide |
| Sulfadoxine/pyrimethamine | Fair | Poor | C | Worldwide, but restricted in US |
| Note: Prescribers and patients are urged to refer to the CDC reference about pregnancy in malaria (wwwn.cdc.gov/travel/contentMalariaPregnantPublic.aspx) and to specific country information regarding sensitivities of malaria (wwwn.cdc.gov/travel/destinationList.aspx). | ||||
| * Pregnancy class C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women, despite potential risks. | ||||
| * Pregnancy class D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women, despite potential risks. | ||||
| † Monitor patients for maternal hypoglycemia. | ||||
| ‡ There is no evidence of teratogenicity, but primaquine is associated with fetal intravascular hemolysis. | ||||
Chemoprophylaxis lowers rates of maternal infection
Although prophylaxis for pregnant patients traveling to malarial regions is a public concern, data for decision-making must be extrapolated from the available evidence, which is based primarily on women living in endemic areas. In a Cochrane systematic review, antimalarials were found to decrease the incidence of maternal infections (relative risk [RR]=0.27; 95% confidence interval [CI], 0.17–0.44) and reduce maternal anemia (RR=0.62; 95% CI, 0.50–0.78) in low-parity women—ie, during a first or second pregnancy.3
In low-parity women, these drugs were also found to decrease perinatal death (RR=0.73; 95% CI, 0.53–0.99) and low birth weight (RR=0.57; 95% CI, 0.46–0.72) associated with malarial infection. When used in all parity groups, antimalarials were somewhat less effective, yet still reduced maternal infections (RR=0.53; 95% CI, 0.33–0.86); the effects were similar with all antimalarials tested.3,4
Chloroquine, mefloquine are safe in pregnancy, doxycycline is not
While chemoprophylaxis in pregnancy appears efficacious, a major question remains—which agents are safest for both the woman and fetus? Some drugs routinely used in nonpregnant individuals should not be offered to pregnant women because of known direct effects on the fetus. Doxycycline is teratogenic, and primaquine poses a significant risk of fetal intravascular hemolysis in G6PD-deficient fetuses.5 Other drugs, such as atovaquone/proguanil and artesunate, are not well studied in pregnancy, and therefore are not recommended for use unless other options are not available.2,6