Cumulative Febrile, Respiratory, and Diarrheal Illness among Infants in Rural Guatemala and their Association with Neurodevelopmental and Growth Outcomes.

ObjectiveWe aimed to evaluate the association between cumulative illness with neurodevelopment and growth outcomes in a birth cohort of Guatemalan infants. Study DesignFrom June 2017 to July 2018, infants 0-3 months of age living in a resource-limited region of rural southwest Guatemala were enrolled and completed weekly at-home surveillance for caregiver-reported cough, fever and vomiting/diarrhea. They also underwent anthropometric assessments and neurodevelopmental testing with the Mullen Scales of Early Learning (MSEL) at enrollment, six months, and one year. ResultsOut of 499 enrolled infants, 430 (86.2%) completed all study procedures and were included in the analysis. At 12-15 months of age, 140 (32.6%) infants had stunting (length-for-age Z [LAZ] score <-2 SD) and 72 (16.7%) had microcephaly (occipital-frontal circumference [OFC] <-2 SD of the mean). In multivariable analysis, greater cumulative weeks of reported cough illness (beta=-0.08/illness-week, p=0.06) and febrile illness (beta=-0.36/illness-week, p<0.001) were marginally or significantly associated with lower MSEL Early Learning Composite (ELC) Score at 12-15 months, respectively; there was no association with any illness (cough, fever, and/or vomiting/diarrhea; p=0.27) or with cumulative weeks of diarrheal/vomiting illness alone (p=0.66). No association was shown between cumulative weeks of illness and stunting or microcephaly at 12-15 months. ConclusionsThese findings highlight the negative cumulative consequences of frequent febrile and respiratory illness on neurodevelopment during infancy. Future studies should explore the inflammatory profile associated with these syndromic illnesses and their impact on neurodevelopment in the first years of life.