1. Objectives

To assess the effects of antihelminthics for soil-transmitted helminths during the second or third trimester of pregnancy on maternal anaemia and pregnancy outcomes

2. How studies were identified

The following databases were searched in January 2015:

• Cochrane Pregnancy and Childbirth Group’s Register
• CENTRAL (The Cochrane Library 2015)
• MEDLINE
• Embase
• CINAHL

Reference lists were also hand-searched

3. Criteria for including studies in the review

3.1 Study type

Randomized controlled trials, including cluster-randomized trials

3.2 Study participants

Women in the second or third trimester of pregnancy

3.3 Interventions

Antihelminthics versus placebo or no treatment

(Both treatment and control groups were required to receive any co-interventions used)

3.4 Primary outcomes

• Maternal anaemia in third trimester (haemoglobin <11 g/dL)

Secondary outcomes included low birth weight (<2500 g), preterm birth before 37 weeks’ gestation, perinatal mortality (fetal death >28 weeks’ gestation and neonatal death <7 days of life), and infant survival at six months

4. Main results

4.1 Included studies

Four randomized controlled trials, enrolling 4265 women, were included in this review

• Sample sizes ranged from 103 to 2507 women
• One trial was a 2 x 2 factorial design with the following arms: i) daily iron-folate supplements and albendazole (single 400 mg dose), ii) daily iron-folate supplements and placebo albendazole, iii) placebo iron-folate supplements and albendazole (single 400 mg dose), and iv) placebo only
• In another 2 x 2 factorial design trial, women were assigned to receive i) albendazole (single 400 mg dose) and placebo, ii) praziquantel (40 mg/kg) and placebo, iii) albendazole (single 400 mg dose) and praziquantel (40 mg/kg), or iv) placebo only
• One trial assigned women to receive i) ivermectin, ii) albendazole (single 400 mg dose), or iii) a combination of ivermectin and albendazole
• In one trial women were randomized to receive either mebendazole (single 500 mg dose) plus a daily iron supplement or a single dose placebo plus a daily iron supplement
• In all trials, women with severe anaemia (haemoglobin <80 g/L or <70 g/L) were excluded and interventions began in the second trimester

4.2 Study settings

• Peru, Sierra Leone, and Uganda (2)
• All study areas were endemic for soil-transmitted helminths

4.3 Study settings

How the data were analysed
Antihelminthics were compared to no treatment or placebo. Where studies had more than two treatment arms, groups were combined to create a single pair-wise comparison. Dichotomous data were summarized using risk ratios (RR) and 95% confidence intervals (CI). Where substantial heterogeneity was detected and a summary estimate was still considered meaningful, random effects models were employed. The following subgroup analyses were planned to explore potential sources of heterogeneity:

• Differences in type, dosage, duration, and frequency of antihelminthics
• Differences in baseline infant mortality
• Co-interventions other than antihelminthics
• Prevalence of malaria

Results
Maternal anaemia in the third trimester
Pooled analysis of four trials including 3266 pregnant women demonstrated no statistically significant effect of a single dose of antihelminthics in the second trimester on maternal anaemia in the third trimester in comparison to placebo (RR 0.94, 95% CI [0.81 to 1.10]). Subgroup analysis of studies including the co-intervention iron supplementation in addition to antihelminthics also showed no statistically significant effect (RR 0.76, 95% CI [0.47 to 1.23], 3 trials/1290 women).

Additional outcomes
In three trials including 3255 participants, a single dose of antihelminthics in the second trimester had no effect on low birth weight (RR 1.00, 95% CI [0.79 to 1.27]). Pooled analysis of data from two trials reporting on the outcome preterm birth demonstrated no statistically significant effect of antihelminthics (RR 0.88, 95% CI [0.43 to 1.78], 2 trials/1318 participants). The risk of perinatal mortality was not reduced with the use of antihelminthics (RR 1.09, 95% CI [0.71 to 1.67], 2 trials/3385 women). None of the included studies reported on the outcome infant survival at six months.

5. Additional author observations*

Two of the four trials were at unclear risk of bias for allocation concealment. The GRADE quality of evidence rating for the primary outcome, maternal anaemia in the third trimester, was of low quality. Other outcomes were rated as being of moderate quality.

On the basis of the limited evidence reviewed, a single dose of antihelminthics in the second trimester of pregnancy had no effect on maternal anaemia, low birth weight, preterm birth or perinatal mortality. However, as future research is likely to change estimates of the effects, no firm conclusions may be drawn at this point.

In the Sierra Leone study, administering an antihelminthic in the second trimester along with iron supplements demonstrated a beneficial effect on maternal anaemia; however, in pooled analysis, no statistically significant effect was observed. Further trials are therefore needed to investigate this treatment regime. In addition, further large, high-quality randomized trials are needed to establish the effect of antihelminthics on maternal anaemia and pregnancy outcomes.