Research Article: Insecticide-Treated Nets for the Prevention of Malaria in Pregnancy: A Systematic Review of Randomised Controlled Trials

Date Published: March 27, 2007

Publisher: Public Library of Science

Author(s): Carol Gamble, Paul J Ekwaru, Paul Garner, Feiko O. ter Kuile, Stephen J Rogerson

Abstract: BackgroundProtection from malaria with insecticide-treated bednets (ITNs) during pregnancy is widely advocated, but evidence of benefit has been inconsistent. We undertook a systematic review of randomised trials.Methods and FindingsThree cluster-randomised and two individually randomised trials met the inclusion criteria; four from Africa (n = 6,418) and one from Thailand (n = 223). In Africa, ITNs compared to no nets increased mean birth weight by 55 g (95% confidence interval [CI] 21–88), reduced low birth weight by 23% (relative risk [RR] 0.77, 95% CI 0.61–0.98), and reduced miscarriages/stillbirths by 33% (RR 0.67, 0.47–0.97) in the first few pregnancies. Placental parasitaemia was reduced by 23% in all gravidae (RR 0.77, 0.66–0.90). The effects were apparent in the cluster-randomised trials and the one individually randomised trial in Africa. The trial in Thailand, which randomised individuals to ITNs or untreated nets, showed reductions in anaemia and fetal loss in all gravidae, but not reductions in clinical malaria or low birth weight.ConclusionsITNs used throughout pregnancy or from mid-pregnancy onwards have a beneficial impact on pregnancy outcome in malaria-endemic Africa in the first few pregnancies. The potential impact of ITNs in pregnant women and their newborns in malaria regions outside Africa requires further research.

Partial Text: Approximately 50 million pregnant women are exposed to malaria each year. Pregnant women are more susceptible to malaria, placing both mother and fetus at risk of the adverse consequences [1–3]. In areas of low and unstable transmission, such as in many regions in Asia and the Americas, women do not acquire substantial antimalarial immunity, and are susceptible to episodes of acute and sometimes severe malaria, and fetal and maternal death [4]. In areas with stable malaria transmission, such as in most of sub-Saharan Africa, infection with Plasmodium falciparum in pregnancy is characterised by predominantly low-grade, sometimes sub-patent, persistent or recurrent parasitaemia. These infections frequently do not result in acute symptoms yet are a substantial cause of severe maternal anaemia [5] and of low birth weight (LBW) [3], and as such are a potential indirect cause of early infant mortality [6–8]. Because most of these infections remain asymptomatic, and therefore undetected and untreated, prevention of malaria in pregnancy is especially important in these settings.

A protocol was developed for this review [11], and the standard search strategy of the Cochrane Infectious Diseases Group was used to identify potentially relevant trials [12]. The inclusion criteria were all trials that randomised individuals (pregnant women) or clusters (community or antenatal clinics) in areas where malaria transmission occurs. Where cluster-randomised trials were identified, the methods of analysis were checked to ensure that the precision of the data extracted from the reports was correctly estimated. The authors needed to have adjusted for clustering, as ignoring the clustering provides the correct point estimate of the magnitude of the trial effect but may overestimate the precision, resulting in potentially incorrect conclusions [13]. Primary outcomes selected were mean haemoglobin and anaemia, and mean birthweight and LBW; secondary outcomes included peripheral malaria in the mother assessed by finger prick during pregnancy or at birth, placental malaria assessed by microscopy, clinical malaria, pre-term birth, fetal loss (defined as miscarriage or stillbirth), and maternal death.

This systematic review shows that ITNs were associated with some important health benefits for pregnant women and their babies. Women of low gravidity randomised to ITNs delivered fewer LBW babies and were less likely to experience fetal loss (miscarriage or stillbirth). Although the latter was not a primary endpoint in the trials, it is an important outcome. No significant decrease was observed in pre-term deliveries in the single trial that assessed this outcome. The consistent reduction observed in the miscarriage and stillbirth rates suggests that the attributable effect of malaria on fetal loss may be underestimated in malaria-endemic Africa, where most women remain asymptomatic when infected with P. falciparum. Despite the reduction in malaria infections, no overall effect on mean haemoglobin was demonstrated, and data on maternal anaemia were inconsistent.