Effect of drugs to treat intestinal worms from contaminated soil in pregnant women

What is the issue?

Parasitic worm infections from contaminated soil include hookworm, roundworm, and whipworm. These intestinal worms (helminths) feed on blood and can contribute to iron-deficiency anaemia in women of reproductive age. Parasitic worms also release substances that stop blood from clotting, so cause further bleeding. Affected women often experience anorexia, vomiting and diarrhoea, which reduces the supply of essential nutrients for producing blood cells. As a result, the health of pregnant women and their unborn babies can be affected.

Antihelminthics are drugs that force parasitic worms out of the body, either by stunning or killing them, without causing damage to the host. Antihelminthics are highly effective against these worms, but evidence of their beneficial effect and safety when given during pregnancy is limited.

Why is this important?

Women in low- and middle-income countries (LMICs) are especially likely to have worms that can lead to anaemia, since they may be pregnant or lactating for as much as half of their reproductive lives. Women who are anaemic during pregnancy are more likely to have ill health, give birth prematurely, and have low birthweight (LBW) babies with low iron reserves. A lack of iron can reduce the babies' mental abilities and development as well as their physical growth.

What evidence did we find?

We searched for evidence in March 2021 and identified six randomised controlled studies (in 24 reports) that included 7873 pregnant women. All of the included studies were conducted in antenatal clinics within hospitals in LMICs (Uganda, Nigeria, Peru, India, Sierra Leone and Tanzania). All except one of the included trials gave iron supplementation to the women participating in the studies, as well as the antihelminthic drugs.

Evidence from five trials (5745 women) suggests that deworming using a single dose of antihelminthics in the second trimester of pregnancy may reduce maternal anaemia (low-certainty evidence). We are uncertain about the effects on preterm birth (1042 women in 1 study) or perinatal mortality (3356 women in 3 studies), with low-certainty evidence for both outcomes. Antihelminthics probably make little or no difference to LBW babies (3301 women in 4 studies) or birthweight (3301 women in 4 studies), with moderate-certainty evidence for both outcomes. The number of women with worms was reduced (2488 women in 2 studies; low-certainty evidence).

What does this mean?

Antihelminthic drugs given during the second trimester of pregnancy may reduce maternal anaemia and the number of women with worms, but with no impact on other maternal or pregnancy outcomes. Further research is needed among particular groups of women and on the effectiveness of additional interventions with antihelminthics, including health education.

Authors' conclusions: 

The evidence suggests that administration of a single dose of antihelminthics in the second trimester of pregnancy may reduce maternal anaemia and worm prevalence when used in settings with high prevalence of maternal helminthiasis. Further data is needed to establish the benefit of antihelminthic treatment on other maternal and pregnancy outcomes.

Future research should focus on evaluating the effect of these antihelminthics among various subgroups in order to assess whether the effect varies. Future studies could also assess the effectiveness of co-interventions and health education along with antihelminthics for maternal and pregnancy outcomes.

Read the full abstract...
Background: 

Helminthiasis is an infestation of the human body with parasitic worms. It is estimated to affect 44 million pregnancies, globally, each year. Intestinal helminthiasis (hookworm infestation) is associated with blood loss and decreased supply of nutrients for erythropoiesis, resulting in iron-deficiency anaemia. Over 50% of the pregnant women in low- and middle-income countries (LMIC) suffer from iron-deficiency anaemia. Though iron-deficiency anaemia is multifactorial, hookworm infestation is a major contributory cause in women of reproductive age in endemic areas. Antihelminthics are highly efficacious, but evidence of their beneficial effect and safety when given during pregnancy has not been established. This is an update of a Cochrane Review last published in 2015.

Objectives: 

To determine the effects of mass deworming with antihelminthics for soil-transmitted helminths (STH) during the second or third trimester of pregnancy on maternal and pregnancy outcomes.

Search strategy: 

For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) (8 March 2021) and reference lists of retrieved studies.

Selection criteria: 

We included all prospective randomised controlled trials evaluating the effect of administration of antihelminthics versus placebo or no treatment during the second or third trimester of pregnancy; both individual-randomised and cluster-randomised trials were eligible. We excluded quasi-randomised trials and studies that were only available as abstracts with insufficient information.

Data collection and analysis: 

Two review authors independently assessed trials for inclusion and risk of bias, extracted data, checked accuracy and assessed the certainty of the evidence using the GRADE approach.

Main results: 

We included a total of six trials (24 reports) that randomised 7873 pregnant women. All of the included trials were conducted in antenatal clinics within hospitals in LMICs (Uganda, Nigeria, Peru, India, Sierra Leone and Tanzania). Among primary outcomes, five trials reported maternal anaemia, one trial reported preterm birth and three trials reported perinatal mortality. Among secondary outcomes, included trials reported maternal worm prevalence, low birthweight (LBW) and birthweight. None of the included studies reported maternal anthropometric measures or infant survival at six months. Overall, we judged the included trials to be generally at low risk of bias for most domains, while the certainty of evidence ranged from low to moderate.

Analysis suggests that administration of a single dose of antihelminthics in the second trimester of pregnancy may reduce maternal anaemia by 15% (average risk ratio (RR) 0.85, 95% confidence interval (CI) 0.72 to 1.00; I²= 86%; 5 trials, 5745 participants; low-certainty evidence). We are uncertain of the effect of antihelminthics during pregnancy on preterm birth (RR 0.84, 95% CI 0.38 to 1.86; 1 trial, 1042 participants; low-certainty evidence) or perinatal mortality (RR 1.01, 95% CI 0.67 to 1.52; 3 trials, 3356 participants; low-certainty evidence).

We are uncertain of the effect of antihelminthics during pregnancy on hookworm (average RR 0.31, 95% CI 0.05 to 1.93; Tau² = 1.76, I² = 99%; 2 trials, 2488 participants; low-certainty evidence). Among other secondary outcomes, findings suggest that administration of antihelminthics during pregnancy may reduce the prevalence of trichuris (average RR 0.68, 95% CI 0.48 to 0.98; I²=75%; 2 trials, 2488 participants; low-certainty evidence) and ascaris (RR 0.24, 95% CI 0.19 to 0.29; I²= 0%; 2 trials, 2488 participants; moderate-certainty evidence). Antihelminthics during pregnancy probably make little or no difference to LBW (RR 0.89, 95% CI 0.69 to 1.16; 3 trials, 2960 participants; moderate-certainty evidence) and birthweight (mean difference 0.00 kg, 95% CI -0.03 kg to 0.04 kg; 3 trials, 2960 participants; moderate-certainty evidence).