Effect of administration of antihelminthics for soil-transmitted helminths during pregnancy

Up to 740 million people worldwide may suffer from hookworm infection, which leads to both nutrient deficiency and anaemia. Limited data from three trials suggest that, in areas endemic for soil-transmitted helminths, a single dose of an antihelminthic drug is unlikely to reduce maternal anaemia and related adverse outcomes for the mother and her baby.

RHL Commentary by Kumar N

1. INTRODUCTION

Soil-transmitted helminths – which include hookworm, roundworms and whipworms – have been recognized as an important public health problem in many developing countries (1, 2). It is estimated that 576–740 million people worldwide suffer from hookworm infection (both Ancylostoma duodenale and Ancylostoma americana) (3), which, owing to chronic blood loss form the intestine, leads to both nutrient deficiency and anaemia.

Iron-deficiency anaemia itself is the most common consequence of nutrient deficiency in the world. It is estimated that more than 50% of women of reproductive age in developing countries are anaemic. There is a strong association between the degree of anaemia during pregnancy and pregnancy outcomes, namely low birth weight of infant, preterm birth, perinatal mortality and infant survival. Theoretically, there is considerable potential to reduce the impact of anaemia in pregnancy by treating pregnant women with anthelminthic drugs in areas where hookworm infestation is common.

This review sought to determine the effects of administration of antihelminthics for soil-transmitted helminths during the second and third trimesters of pregnancy on maternal anaemia and pregnancy outcomes.

2. METHODS OF THE REVIEW

The authors of the review performed an extensive search through the electronic Cochrane Pregnancy and Childbirth Group’s trial register. The reviewers were looking for randomized controlled trials involving administration of antihelminthics in pregnant women in the second or third trimester.

The risk of bias in the included trials was assessed using the criteria outlined in Cochrane handbook of systematic reviews of interventions (4). Each author extracted the data independently using an agreed form. The extracted data were entered and analysed using the Review Manager Software (RevMan 2008).

3. RESULTS OF THE REVIEW

Three randomized controlled trials assessing the effects of administration of antihelminthics during second or third trimester of pregnancy were included. These trials, which included 1329 pregnant women, evaluated maternal and perinatal outcomes associated with the administration of antihelminthics, including maternal anaemia (defined as Hb <11.0g/dl), low birth weight (< 2500 g), preterm birth (before 37 weeks of gestation), perinatal mortality and infant survival at 6 months.

The trials were conducted in Sierra Leone (184 women), Peru (1042 women) and Uganda (103 women) and included women in the second trimester of their pregnancy. The trials had evaluated, through a randomized placebo-controlled design, outcomes of a single dose of an antihelminth (albendazole 400 mg or mebendazole 500 mg). Two studies also had iron supplementation and iron plus folic acid supplementation as a co-intervention in both groups.

The administration of a single dose of an antihelminth, with or without iron supplementation during the second and third trimesters of pregnancy, had no impact on maternal anaemia when compared with iron supplementation alone [risk ratio (RR) 0.76; 95% confidence interval (CI) 0.39–1.45; 2 studies, n = 1017). Also, no effect of deworming was measured on the outcomes of low birth weight (RR 0.94; 95% CI 0.61–1.42 (on study; n = 950), perinatal mortality (RR 1.10; 95% CI 0.55–2.22 (2 studies, n = 1089) and preterm birth (RR 0.85; 95% CI 0.38–1.87 (1 study, n = 984).

None of the studies indicated whether any information had been collected on infant survival at 6 months of age. A sensitivity analysis for the risk of bias due to incomplete results on perinatal mortality was not conducted since only three studies were included in analysis.

4. DISCUSSION

4.1. APPLICABILITY OF THE RESULTS

The review did not find sufficient evidence to recommend use of antihelminths in pregnant women to reduce the risks associated with anaemia in pregnancy. The three studies included in the review were done in developing countries known to have a high prevalence of soil-transmitted helminths. Since hookworm is primarily responsible for causing anaemia and the frequency of hookworm in the three studies varied from 38 % to 65.6 %, the role of antihelminthic in improving the anaemic status of the pregnant women could have been best studied by highlighting the results of this group, and avoiding those women who were possibly anaemic due to causes other than iron deficiency. The findings of the review are relevant to communities with high rates of hookworm infestation.

4.2. IMPLEMENTATION OF THE INTERVENTION

At the present time there is no justification at the present time to undertake mass deworming programmes to reduce maternal anaemia and improve clinical outcomes for mothers and their babies. In a subset of the study in Sierra Leone, it was found that a single dose of antihelminth treatment early in the second trimester of pregnancy, along with iron and folate, had a beneficial effect on maternal anaemia. If this result can be confirmed in a larger trial, it could have significant implications of reducing anaemia in pregnant women. It would also indicate to what extent infection with soil-transmitted helminths contributes to anaemia in the population.

4.3. IMPLICATIONS FOR RESEARCH

In the trials included in the review women were given an antihelminthic drug without prior testing to determine infestation with soil-transmitted helminths. Future research should include studies carried out only on pregnant women that had positive stool tests with intestinal helminths, before being randomized into various study groups. Since there is a direct relationship between the intensity of hookworm infestation and blood loss (5), stratification of study subjects by the intestinal load of helminths would be useful in future studies.

Sources of support: None

Acknowledgements: None

References

  • Gbakima AA, Sherpard M. White P. Intestinal helminth infection in rural school children in Njala Sierra Leone. East African Medical Journal 1994;71:792-796.
  • Gupta MC, Mithal S, Arora KL, Tandon BN. Effects of periodic deforming on nutritional status of Ascidia infected pre-school children receiving supplementary food. The Lancet 1977;3:108-110.
  • Bethony Brooker Albonico. (2006) Soil transmitted helminth infections: ascariasis, trichuriasis and hookworm. Lancet 367: 1521-32
  • Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions Version 5.0.2 (updated September 2009). The Cochrane Collaboration; 2009. Available from www.cochrane-handbook.org.
  • Larocque R, Casapia M, Gotuzzo E, Gyorkos TW, American Journal of Tropical Medicine and Hygiene 2005;73:783-789.

This document should be cited as: Kumar N. Effect of administration of antihelminthics for soil-transmitted helminths during pregnancy: RHL commentary (last revised: 1 December 2009). The WHO Reproductive Health Library; Geneva: World Health Organization.

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