Uncomplicated Malaria in Infancy and Neurodevelopment at 1 and 6 Years: Evidence From the MiPPAD Birth Cohort Study...

In malaria-endemic regions, repeated episodes of uncomplicated malaria during infancy are common; however, their associations with neurodevelopment remain unclear. We examined relationships between malaria frequency in infancy and neurodevelopmental outcomes in early and middle childhood, using data from the APEC birth cohort nested within the MiPPAD birth cohort study of Benin. Children were enrolled between January 2010 and June 2011 and followed from birth to 24 months of age. Malaria was assessed at scheduled visits at 6, 9 and 12 months using both PCR and microscopy, and at unscheduled visits for symptomatic episodes using only microscopy; haemoglobin was measured concurrently. Neurodevelopment was assessed at age 1 and 6 years. Analyses included 311 children at 1-year and 248 at 6-year assessments. Malaria exposure was defined as the number of episodes from birth to 1-year neurodevelopmental assessment for three measures: (i) total malaria (PCR- or microscopy-positive), (ii) symptomatic malaria (positive with fever) and (iii) malaria with anaemia (positive with haemoglobin < 11.0 g/dL). Associations with neurodevelopment and haemoglobin's mediating role were assessed using adjusted generalized linear models and mediation analysis. We found that a higher number of symptomatic malaria episodes during infancy was associated with lower motor scores at age one (β: -2.81, [-4.73, -0.89]) and age six (β: -1.43, [-2.65, -0.22]), partially and potentially mediated by haemoglobin concentration. Malaria with anaemia was associated with lower motor scores at age one (β: -1.57, [-3.04, -0.10]) and age six (β: -0.96, [-1.86, -0.05]). No consistent associations were observed with cognitive outcomes. These findings indicate that uncomplicated malaria in infancy is an important risk factor for impaired child development and should not be overlooked. Integrating anaemia screening and management into malaria control and routine child health services may help mitigate long-term developmental impacts in malaria-endemic settings.