To investigate whether currently available antimalarial drugs can be safely administered during pregnancy.

MEDLINE was searched and reviews of infectious disease textbooks were examined. Manufacturers of antimalarial agents were contacted for all relevant published and unpublished literature.

Study designs of evaluations included in the review

Randomised controlled trials (RCTs), comparative studies, case reports and case series were included.

Specific interventions included in the review

Antimalarial drugs: quinoline derivatives (quinine, chloroquine, mefloquine, primaquine), dihydrofolate reductase inhibitors (proguanil and chlorproguanil, pyrimethamine), sulphonamides and sulphones (sulphonamides, dapsone, sulphonamide and sulphone combinations), antibacterials (tetracycline, doxycycline), and other drugs (halofantrine, artemisinin).

Participants included in the review

Pregnant women taking antimalarial drugs were included.

Outcomes assessed in the review

Birth outcomes: abortion, pre-term delivery, stillbirth, perinatal death, congenital abnormality and lactation.

How were decisions on the relevance of primary studies made?

The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.

The authors do not state that they assessed validity.

The authors do not state how the data were extracted for the review, or how many of the authors performed the data extraction.

How were the studies combined?

A narrative overview was undertaken.

How were differences between studies investigated?

Differences between the studies were described narratively.

Quinoline derivatives: 26 studies.

Dihydrofolate reductase inhibitors: 7 studies.

Sulphonamides and sulphones: 14 studies.

Antibacterials: 9 studies.

Other drugs: 6 studies.

High dose of quinine: stimulation of the pregnant uterus; deafness and optic nerve hypoplasia in children.

Standard (malaria) dose of quinine: no evidence of increased risk of abortion or pre-term delivery; increased quinine-stimulated insulin release.

High dose of chloroquine: rare case reports of ototoxicity; overall incidence of congenital abnormalities not increased.

Standard (malaria) dose of chloroquine: no evidence of increased risk of premature delivery, stillbirth or perinatal death, or congenital abnormality. Standard (malaria) dose of mefloquine: no overall increase in congenital abnormalities.

Primaquine: increased risk of intravascular haemolysis in foetus or infant.

Standard (malaria) dose of proguanil and chlorproguanil: no evidence of toxic effects; reduced plasma concentrations.

High dose of pyrimethamine: protective effect of drug on foetuses of women with toxoplasmosis.

Standard (malaria) dose of pyrimethamine: no overall increase in congenital abnormalities, but it has been implicated in case reports.

High dose of sulphonamides: no clear increase in congenital abnormalities; no evidence of kernicterus in neonates.

Standard (malaria) dose of sulphonamides: not used alone for malaria.

High dose of dapsone: no clear increase in congenital abnormalities; no evidence of kernicterus in neonates.

High dose of sulphonamide and sulphone combination: no clear increase in congenital abnormalities; no evidence of kernicterus in neonates.

Standard (malaria) dose of sulphonamide and sulphone combination: no increase in congenital abnormalities; case reports of minor musculoskeletal congenital abnormalities.

High dose of tetracycline: abnormal skeletal development; permanent deposits in teeth; discolouration of the cornea and lens.

High dose of doxycycline: some case reports of congenital abnormalities.

Standard (malaria) dose of halofantrine: no congenital abnormality in the 2 cases reported.

Standard (malaria) dose of artemisinin: no congenital abnormality reported in the limited data available.

With the exception of the tetracyclines, there is no evidence to suggest that, at standard dosages, any of the antimalarial drugs are teratogenic. Primaquine is not recommended because of the potential risk of haemolytic effects in the fetus. Rates of spontaneous abortion and birth defects were comparable in pregnant women taking mefloquine, compared with combined prophylaxis such as chloroquine-proguanil or pyrimethamine-sulfadoxine, in the first trimester of pregnancy. Standard doses of quinine do not increase the risk of abortion or pre-term delivery. Therapeutic mefloquine dose not provoke hypoglycaemia. There is no evidence to suggest the hypothetical risk of kernicterus in the newborn, following exposure to antimalarial drugs containing sulphonamides or sulphones prior to delivery. Documentation of the safety of doxycycline, halofantrine, and the artemisinin derivatives in the treatment of malaria in pregnant women, is currently limited.

Study type varied greatly, ranging from RCTs to case reports, and many different drugs were evaluated. The criteria for including primary studies are not explicitly described.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.