br Conclusion br Acknowledgements The
Acknowledgements The authors would like to thank the funders of this project, the Canadian Institute of Health Research (CIHR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Introduction Evidence from low- and middle-income countries (LMICs) has highlighted the importance of ensuring optimal conditions in early childhood, and in particular, the first two years of life, for healthy development in the short and long-term (Grantham-McGregor, Cheung, & Cueto, 2007; Martorell, Horta, & Adair, 2010; Victora, Adair, & Fall, 2008; Victora, de Onis, Hallal, Blössner, & Shrimpton, 2010). Poverty is a major underlying cause of developmental deficits, through increased nutritional deficiencies and infection, an inadequate home environment and stimulation, and low parental education (Grantham-McGregor et al., 2007). These risk factors can impact plk1 inhibitor development and thus cognitive functioning in early life, and later school achievement and productivity in adulthood (Martorell et al., 2010; Victora et al., 2008). Thus, appropriate and integrated interventions must be provided to improve early child development, reduce health inequities, and provide those most vulnerable populations an opportunity to escape the vicious cycle of poverty (Grantham-McGregor et al., 2007). Interventions to improve child development include micronutrient supplementation and breastfeeding, and targeting the social components linked to poverty, such as mother–child interactions and child stimulation (Engle, Fernald, & Alderman, 2011; Grantham-McGregor, Fernald, Kagawa, & Walker, 2014; Walker, Wachs, & Grantham-McGregor, 2011). There has been less evidence on the potential benefits of interventions for infections in early childhood on short or long-term development. The soil-transmitted helminth (STH) disease cluster (i.e. Ascaris, Trichuris and hookworm) is common in the most vulnerable populations in LMICs. STHs persist in contaminated environments with poor sanitation and limited access to improved water sources. The impact of providing large-scale single-dose anthelminthic treatment (i.e. deworming) on cognition has been studied almost exclusively in school-age children. STH infection is thought to primarily impact child development indirectly by affecting host nutrition, mainly through competition for nutrients and energy; however, direct pathways between infection and cognition have also been hypothesized (Kvalsvig & Albonico, 2013; Hall, Hewitt, Tuffrey, & de Silva, 2008). Some observational studies and randomized controlled trials (RCTs) have shown a benefit of deworming (mainly through a reduction in hookworm or Trichuris infection) on cognition, measured directly through psychometric tests, or indirectly through school indicators such as school performance and attendance (Sakti, Nokes, & Hertanto, 1999; Nokes and Bundy , 1993; Nokes et al., 1992; Ezeamama, McGarvey, & Hogan, 2012). However, the combined evidence is mixed, and a recent Cochrane review was unable to detect an overall significant benefit of deworming on cognition in school-age children (Taylor-Robinson, Maayan, Soares-Weiser, Donegan, & Garner, 2015). In addition, the validity of previous research which had demonstrated a positive effect of deworming on school indicators, such as attendance, has been called into question (Hicks, Kremer, & Miguel, 2015; Aiken, Davey, Hargreaves, & Hayes, 2015). The evidence base in preschool-age children is even more limited. One cross-sectional study found some evidence for a link between intestinal parasite infections (not limited to STH) and deficient scores on the Denver Developmental Screening Test II in children living in rural Nicaragua (Oberhelman, Guerrero, & Fernandez, 1998). This relationship did not persist in multivariable analysis nor in a subgroup analysis of children under 24 months of age. Stoltzfus, Kvalsvig, and Chwaya (2001) conducted an RCT on deworming and development in preschool-age children. Although not statistically significant, there was a trend towards a benefit of deworming on language and gross motor development.