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Background An estimated 30% of women in Sub-Saharan Africa suffer from soil-transmitted helminth infection during pregnancy (SHIP), which has been shown to increase risk of pre-term birth, low birth weight, and maternal anemia. A previous study in Benin found that SHIP was associated with impaired cognitive and gross motor development scores in 635 one-year-old children. The objective of the present study was to follow children prospectively to investigate whether the association between SHIP and child neurocognitive and behavioral development persisted at age six. Principal findings Our prospective child cohort included 487 live-born singletons of pregnant women enrolled in the Malaria in Pregnancy Preventive Alternative Drugs clinical trial in Allada, Benin. SHIP was assessed at three antenatal visits (ANVs) through collection and testing of stool samples. Neurocognitive and behavioral development was assessed in six-year-old children by trained investigators using the Kaufman Assessment Battery for Children 2nd edition and the parent-reported Strengths and Difficulties Questionnaire (SDQ). Multiple linear regression models generated coefficients and 95% confidence intervals and potential mediating factors were tested. Prevalence of SHIP was 13% at the 1st ANV, 9% at the 2nd ANV, and 1% at delivery. SHIP was not associated with low neurocognitive scores in children at six years. Higher SDQ internalizing scores, indicating increased emotional impairments in children, were associated with helminth infection at the 2nd ANV/delivery 1.07 (95% CI 0.15, 2.00) and at least once during pregnancy 0.79 (95% CI 0.12, 1.46) in adjusted models. Mediation analysis did not reveal significant indirect effects of several mediators on this association. Conclusions Our study shows that while SHIP is not associated with impaired long-term neurocognitive development, infections may have significant negative impacts on emotional development in six-year-old children. SHIP remains a critical public health issue, and adequate prevention and treatment protocols should be enforced in low- and middle-income countries., Author summary Soil-transmitted helminth infections impact 1.5 billion individuals, primarily in low- and middle- income countries, each year and contribute to malnutrition, anemia, and impaired neurocognitive development in children. However, these infections in pregnancy and their impact on offspring have been less studied. One previous study found associations between soil-transmitted helminth infection during pregnancy and impaired cognitive functioning in offspring one year after birth. The current study aimed to follow these children prospectively until six years in order to confirm whether these associations persisted or not. Infections during pregnancy were no longer associated with cognitive or motor functioning in children; however, infections were associated with impaired behavioral development. Animal-based models have hypothesized maternal inflammation and poor birth outcomes to be the mechanisms behind this relationship; however, our findings did not support these mechanisms. This is one of very few prospective cohort studies in Sub-Saharan Africa to investigate these associations, and more research is needed to corroborate results. Limitations include limited power and the possibility that results are due to chance from multiple statistical tests. Adequate and accessible prevention and treatment efforts in pregnancy and childhood should be provided to populations in low- and middle- income countries at high risk of infection.

Global efforts to control morbidity associated with soil-transmitted helminth infections (STH) have focused largely on the targeted treatment of high-risk groups, including children and pregnant women. However, it is not clear when such programs can be discontinued and there are concerns about the sustainability of current STH control programs. The DeWorm3 project is a large multi-country community cluster randomized trial in Benin, India and Malawi designed to determine the feasibility of interrupting the transmission of STH using community-wide delivery of mass drug administration (MDA) with anthelmintics over multiple rounds. Here, we present baseline data and estimate key epidemiological parameters important in determining the likelihood of transmission interruption in the DeWorm3 trial. A baseline census was conducted in October-December 2017 in India, November-December 2017 in Malawi and in January-February 2018 in Benin. The baseline census enumerated all members of each household and collected demographic data and information on occupation, assets, and access to water, sanitation and hygiene (WASH). Each study site was divided into 40 clusters of at least 1,650 individuals per cluster. Clusters were randomized to receive twice yearly community-wide MDA with albendazole (GSK) targeting eligible individuals of all ages (20 clusters), or to receive the standard-of-care deworming program targeting children provided in each country. In each site, a randomly selected group of 150 individuals per cluster (6,000 total per site) was selected from the baseline census using stratified random sampling, and each individual provided a single stool sample for analysis of STH infection using the Kato-Katz technique. Study site, household and individual characteristics were summarized as appropriate. We estimated key epidemiological parameters including the force of infection and the degree of parasite aggregation within the population. The DeWorm3 sites range in population from 94,969 to 140,932. The population age distribution varied significantly by site, with the highest proportion of infants and young children in Malawi and the highest proportion of adults in India. The baseline age- and cluster-weighted prevalence, as measured by Kato-Katz, varied across sites and by species, Baseline hookworm prevalence in India was 21.4% (95% CI: 20.4–22.4%), while prevalence of Ascaris and Trichuris by Kato-Katz was low (0.1% and 0.3% overall). In Malawi, the overall age- and cluster-weighted STH prevalence was 7.7% (95% CI: 7.1–8.4%) predominantly driven by hookworm infections (7.4%) while Ascaris (0.1%) and Trichuris (0.3%) infections were rare. In Benin, the overall age- and cluster-weighted prevalence was significantly lower (5.6%, 95% CI: 5.1–6.2%) and Ascaris (2.0%, 95% CI: 1.6–2.3%) was more common than in other sites. Ascaris infections were more likely to be moderate- or heavy-intensity (43.7%, unweighted) compared to hookworm (5.0%). The force of infection for hookworm was highest in adults in India and Malawi but appeared relatively stable across age groups in Benin. These data demonstrate the significant variability between the sites in terms of demography, socio-economic status and environmental characteristics. In addition, the baseline prevalence and intensity data from DeWorm3 suggest that each site has unique epidemiologic characteristics that will be critical in determining correlates of achieving STH transmission interruption in the DeWorm3 trial. Trial registration: The trial was registered at ClinicalTrials.gov (NCT03014167)., Author summary Intestinal parasitic worms, soil-transmitted helminths, are among the most common infectious organisms of humans. In many low-resource settings, these infections result in considerable morbidity, including reductions in childhood growth and development, increased risk of anemia and reductions in future educational achievement and income earning potential. The current global strategy for controlling these infections is through routine deworming of school and pre-school aged children as well as pregnant women. Since many adults and non-school going children are infected with these parasites, the current strategy does not prevent the rapid reinfection of individuals despite repeated treatment. The DeWorm3 trial is a large multi-country trial being conducted in Benin, India and Malawi to test the feasibility of using mass drug administration of deworming medications to all individuals in a community to interrupt these infections in some geographic areas. Here we present baseline data from these communities and estimate the transmission potential of these infections at each of the sites.