The results of a population-based study assessing the outcome of pregnancies of women from the Thai-Burmese border exposed to malaria during the first trimester, and comparing outcomes after chloroquine-based, quinine-based, or artemisinin-based treatments, have been published early online in the Lancet.

The authors note that published evidence on the effects of exposure to malaria and antimalarials during the first trimester of pregnancy is scarce.  Artemisinin combination treatments are recommended by WHO for the treatment of Plasmodium falciparum except in the first trimester as animal data suggest they are embryotoxic.  

Researchers analysed the antenatal records of women in the first trimester of pregnancy who attended the Shoklo Malaria Research Unit (situated on the northwestern border of Thailand) between May 1986 and October 2010.  Those without a valid estimate of gestation, who had malaria in the second or third trimester, or who had an unknown outcome were excluded.  A total of 17,613 women met the inclusion criteria – 16,668 had no malaria during pregnancy and 945 had a single episode in the first trimester.  Those with malaria were treated with chloroquine (45%), quinine (41%), an artemisinin derivative (10%), mefloquine (3%) or other/unknown (<1%). 

The following main results are reported:

• The odds of miscarriage increased in women with asymptomatic malaria (adjusted odds ratio 2.70, 95% CI 2.04-3.59) and symptomatic malaria (3.99, 3.10-5.13), and were similar for Plasmodium falciparum and Plasmodium vivax.

• In women with malaria, additional risk factors for miscarriage included severe or hyperparasitaemic malaria (adjusted odds ratio 3.63, 95% CI 1.15-11.46) and parasitaemia (1.49, 1.25-1.78 for each ten-fold increase in parasitaemia).

• Other risk factors for miscarriage (in all women) included smoking, maternal age, previous miscarriage, and non-malaria febrile illness.

• Higher gestational age at the time of infection was protective (adjusted odds ratio 0.86, 95% CI 0.81-0.91).

• Of 773 women treated for malaria, 566 (73%) delivered and 207 (27%) miscarried: 92 (26%) of 354 after treatment with chloroquine, 95 (27%) of 355 after treatment with quinine, and 20 (31%) of 64 after treatment with artesunate (p=0.71).  Adverse effects related to antimalarial treatment were not observed.

The authors conclude from their findings that a single malaria episode in the first trimester of pregnancy can cause miscarriage.  Although adverse effects related to treatment with quinine, chloroquine or artesunate were not seen, the numbers in the latter group were small.  They conclude that a randomised trial of artemisinin-based therapy in the treatment of malaria in the first trimester is needed to make firm recommendations on the safety of exposure to these medicines during pregnancy.