Insecticide-treated nets for the prevention of malaria in pregnancy: a systematic review of randomised controlled trials

Abstract

Background: Protection 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 findings: Three 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.

Conclusions: ITNs 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.

Figure 1. Effect of ITNs versus No Nets in Africa on Mean Haemoglobin Levels (in Grams/Litre)

The red squares represent the effect estimates of ITNs; the black lines represent the 95% confidence intervals associated with the effect estimates (a line with an arrow indicates that the confidence interval was greater than could be illustrated in the graph). The black diamonds represent the summary effect estimates for the different subgroups (“subtotal”) and for the overall effect (“total”). “Dry” and “wet” refer to the dry and wet seasons. SP+, women randomized to IPTp-SP; SP-, women randomized to receive placebo ITPp (factorial design).

Figure 2. Effect of ITNs versus No Nets in Africa on Mean Birth Weight (in Grams)

The red squares represent the effect estimates of ITNs; the black lines represent the 95% confidence intervals associated with the effect estimates. The black diamonds represent the summary effect estimates for the different subgroups (“subtotal”) and for the overall effect (“total”). “Dry” and “wet” refer to the dry and wet seasons. SP+, women randomized to IPTp-SP; SP-, women randomized to receive placebo ITPp (factorial design).

Figure 3. Effect ITNs versus No Nets in Africa on Placental Malaria

The red squares represent the effect estimates of ITNs; the black lines represent the 95% confidence intervals associated with the effect estimates (a line with an arrow indicates that the confidence interval was greater than could be illustrated in the graph). The black diamonds represent the summary effect estimates for the different subgroups (“subtotal”) and for the overall effect (“total”). Placental malaria was defined as the presence of asexual parasitaemia detectable by microscopy. Data from Shulman et al. [26] are based on 25.8% of all enrolled women, and includes only women who delivered in the hospital. The degree of heterogeneity approached moderate levels (I ² = 49.9%) in the low gravidity group. Similar analysis using random instead of fixed-effect models gave a summary effect of 0.82 (0.61–1.11), 0.72 (0.48–1.08), and 0.79 (0.63–0.98) for low, high, and all gravidae, respectively. SP+, women randomized to IPTp-SP; SP-, women randomized to receive placebo ITPp (factorial design).

Figure 4. Effect of ITNs versus No Nets in Africa on Miscarriage or Stillbirth

The red squares represent the effect estimates of ITNs; the black lines represent the 95% confidence intervals associated with the effect estimates (a line with an arrow indicates that the confidence interval was greater than could be illustrated in the graph). The black diamonds represent the summary effect estimates for the different subgroups (“subtotal”) and for the overall effect (“total”). Data from Shulman et al. [26] refer to stillbirths only. As the event is rare (<10%), the OR reported by Shulman et al. approximates an RR and has been combined with the RRs of Njagi [24] and ter Kuile et al. [27]. SP+, women randomized to IPTp-SP; SP-, women randomized to receive placebo ITPp (factorial design).