A review of randomized controlled trials of routine antimalarial drug prophylaxis during pregnancy in endemic malarious areas

Abstract

Current global recommendations for routine malaria chemoprophylaxis in pregnant women living in endemic malarious areas are not clear. To assist in policy formulation, the evidence from randomized controlled trials was reviewed. The literature was extensively searched, and studies identified were systematically analysed in relation to outcomes in the mother and the baby. Routine chemoprophylaxis appears to have an effect on antenatal morbid episodes and packed cell volume. There is a trend towards higher birth-weight values in chemoprophylaxis groups, which reached statistical significance in some studies. Evidence of an effect on gestation was only examined in one study. The effects on perinatal and neonatal mortality have only been examined in a few studies, with small sample sizes. The analysis questions whether routine malaria chemoprophylaxis is the best use of scarce resources in developing countries, and suggests that chemoprophylaxis might be targeted at anaemic women and primigravidae. Large controlled trials, with treatment available to placebo groups, are required to test whether routine chemoprophylaxis has advantages over early, effective treatment of clinical malaria.

PIP: Pregnant women living in an endemic malarious area require evidence of efficacy of chemoprophylaxis. To this end, a systematic review of the existing evidence derived from randomized controlled trials of chemoprophylaxis was conducted by searching MEDLINE from 1966 to 1992 and EMBASE from 1978 to 1992. All studies that examined antenatal parasitemia showed a significant effect of chemoprophylaxis in reducing the parasitemia prevalence even in multigravidae. Four studies examined hemoglobin or packed cell volume values during late pregnancy. Two studies showed a positive effect with all parties combined. In one study, drug prophylaxis with proguanil was associated with a lower risk of obstetric intervention. A nutritional supplementation of iron and/or folic acid appeared to assist maternal growth in pregnancy and to reduce the risk of abdominal delivery. There was no difference in obstetric intervention between placebo alone (4/14) and proguanil alone (2/23). Only one study reported on maternal mortality, with 1/518 deaths in the experimental and 3/531 deaths in the control group. Two studies examined placental parasitemia and showed that chemoprophylaxis significantly reduced this. Although four studies showed a trend towards higher mean birth weight, this was statistically significant in only one study. Five studies showed a trend towards increased birth weight in primigravidae with chemoprophylaxis. In one, there were significantly fewer low birth-weight infants in the prophylaxis group (4/67) than in the control group (11/50; OR=0.88). One study showed two births greater than 4 kg in the prophylaxis group and none in the placebo group (2/144 mefloquine, 0/143 placebo). Only one study examined the duration of gestation. The trend was towards fewer preterm infants in the treatment group, but the difference was not significant. No study detected an effect on perinatal/neonatal mortality. In two studies, the trend was towards a protective effect in the chemoprophylaxis groups.