Cumulative Febrile, Respiratory, and Gastrointestinal Illness Among Infants in Rural Guatemala and Association With Neurodevelopmental and Growth Outcomes

Abstract

Background: Infectious disease exposures in early life are increasingly recognized as a risk factor for poor subsequent growth and neurodevelopment. We aimed to evaluate the association between cumulative illness with neurodevelopment and growth outcomes in a birth cohort of Guatemalan infants. Methods: From June 2017 to July 2018, infants 0–3 months of age living in a resource-limited region of rural southwest Guatemala were enrolled and underwent 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, 6 months, and 1 year. Results: 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). In multivariable analysis, greater cumulative instances 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 instances of diarrheal/vomiting illness alone (P = 0.66). No association was shown between cumulative instances of illness and stunting or microcephaly at 12–15 months. Conclusions: These findings highlight the negative cumulative consequences of frequent febrile and respiratory illness on neurodevelopment during infancy. Future studies should explore pathogen-specific illnesses, host response associated with these syndromic illnesses, and their association with neurodevelopment.