A double-blind randomized controlled trial of antenatal mebendazole to reduce low birthweight in a hookworm-endemic area of Peru. Albendazole therapy and reduced decline in haemoglobin concentration during pregnancy (Sierra Leone). A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to Bacille Calmette-Guérin (BCG) immunisation [ISRCTN32849447].
To assess the effect on birthweight of antenatal mebendazole plus iron vs. placebo plus iron in a highly hookworm-endemic area.
                Double-blind, randomized controlled trial set in rural and peri-urban communities in the Peruvian Amazon region. A total of 1042 second trimester pregnant women between the ages of 18 and 44 years were recruited from April to November 2003, and followed to July 2004. Women were randomly assigned to receive either mebendazole (500 mg single dose) plus iron supplements (60 mg elemental iron daily) or placebo plus iron supplements. The primary outcome was mean infant birthweight and secondary measures included proportion of low birthweight babies and maternal anaemia.
                The prevalence of hookworm infection was 47.5%. There were no differences between intervention groups in mean birthweight (3104 g vs. 3090 g, P = 0.629), proportion of low birthweight (<2500 g; 8.1%vs. 8.7%, P = 0.755) or maternal anaemia in the third trimester [33.0% (158/479) vs. 32.3% (152/471), P = 0.815]. However, the proportion of very low birthweight (<1500 g) was significantly lower in the mebendazole group [0% (0/479) vs. 1.5% (7/471), P = 0.007].
                This trial provides additional evidence for the use of anthelmintics, over and above iron supplementation, within antenatal care programmes in hookworm-endemic areas. Benefits of de-worming may be higher in countries not having an antenatal iron supplementation programme or where intensity of hookworm infections is higher. WHO recommends that anthelmintic treatment be included in strategies to improve maternal nutrition in areas where hookworms are endemic and anaemia is prevalent. At present, few countries have adopted this recommendation, partly owing to the lack of data to support the adverse effects of hookworms on maternal health. A longitudinal study was conducted on 125 women in Sierra Leone (in 1995/96) to measure the impact of single-dose albendazole (400 mg) and daily iron-folate supplements (36 mg iron and 5 mg folate) on haemoglobin and serum ferritin concentration during pregnancy. Women who received both albendazole and iron-folate supplements experienced no significant change (P > 0.05) in the prevalence of anaemia and iron-deficiency anaemia between the first and third trimesters. These prevalence levels significantly increased (P < 0.05) in women who received either albendazole or iron-folate supplements or neither. After controlling for baseline haemoglobin concentration and season, the mean decline in haemoglobin concentration between the first and third trimester in women who received albendazole was 6.6 g/L less than in women who received the control (P = 0.0034). The corresponding value for iron-folate supplements was 13.7 g/L haemoglobin (P < 0.001). The effects of albendazole and iron-folate supplements were additive. These findings lend support to WHO's recommendation for anthelmintic treatment during pregnancy. Maternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG) immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown.
                In Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG. Interferon-gamma (IFN-gamma) and interleukin (IL)-5 responses to a mycobacterial antigen (crude culture filtrate proteins (CFP) of Mycobacterium tuberculosis) were measured in a whole blood assay. We analysed results for binary variables using chi2 tests and logistic regression. We analysed continuous variables using Wilcoxon's tests.
                Maternal hookworm was associated with reduced maternal IFN-gamma responses to CFP (adjusted odds ratio for IFN-gamma > median response: 0.14 (95% confidence interval 0.02-0.83, p = 0.021). Conversely, maternal hookworm was associated with subsequent increased IFN-gamma responses in their one-year-old infants (adjusted OR 17.65 (1.20-258.66; p = 0.013)). Maternal albendazole tended to reduce these effects.
                Untreated hookworm infection in pregnancy was associated with reduced maternal IFN-gamma responses to mycobacterial antigens, but increased responses in their infants one year after BCG immunisation. The mechanisms of these effects, and their implications for protective immunity remain, to be determined.
The evidence to date is insufficient to recommend use of antihelminthics for pregnant women after the first trimester of pregnancy. More well-designed, large scale randomised controlled trials are needed to establish the benefit of antihelminthic treatment during pregnancy.