Soil-transmitted helminth infection in pregnancy and long-term child neurocognitive and behavioral development: A prospective mother-child cohort in Benin

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 2(nd) 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 1(st) ANV, 9% at the 2(nd) 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 2(nd) 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.

Automated summary

The study followed 487 children born to pregnant women in Allada, Benin and found that soil-transmitted helminth infection during pregnancy did not affect neurocognitive development in six-year-old children, but was associated with impaired emotional development. This highlights the importance of strengthening prevention and treatment efforts for helminth infections in low- and middle-income countries.