BackgroundRecurrent infections are associated with neurodevelopmental (ND) delay in infants, but the primary drivers are poorly understood. Leveraging an infant cohort from rural Guatemala designed to evaluate the effects of post-natal Zika virus on ND (DMID 16-0057), we evaluated the association between cumulative illness and ND delay and stunting.MethodsInfants enrolled at 0-3 months of age underwent weekly at-home surveillance for caregiver-reported syndromic illness, including cough, fever and vomiting/diarrhea for a 12-month period. Anthropometric assessments and ND testing by Guatemalan psychologists using the Mullen Scales of Early Learning (MSEL) were perforrmed at 12-15 months of age. Multivariable generalized linear regression models were used to test associations between syndromic illness in infancy, 12-15-month MSEL Early Learning Composite (ELC) Score, and stunting (height-for-age < -2 SD) at 12-15 months.ResultsThe cohort (n=425) had a mean enrollment age of 1.3 months; 202 (48%) were female, 387 (91%) self-reported a literate mother, and 301 (71%) were breastfeeding at study completion. Infants had reported illness for a median of 16 weeks during the surveillance period; cough was reported most frequently (median=11 weeks, range=0-37 weeks). Lower maternal education (p=0.007) and literacy (p=0.002) as well as infant age (p=0.007) and male gender (p=0.004) were associated with MSEL ELC Score <85 (-1 SD). After adjusting for gender, breastfeeding, age, and maternal literacy, the cumulative number of weeks with reported cough (p=0.0009), fever (p=0.0001), or any syndromic illness (p=0.0007) were associated with decreased 12-month MSEL ECL Score; there was no association with diarrhea/vomiting (p=0.36). There was no association between caregiver-reported syndromic illnesses (any type) and stunting at final study visit.ConclusionIn a cohort of Guatemalan infants, cumulative fever and cough episodes were significantly associated with lower MSEL ELC Score, whereas there was no association with diarrhea/vomiting. In this low-resource community, these findings highlight the potential negative ND consequences of febrile illness and persistent cough in the first year of life. NIAID Contract HHSN272201300015I Task Order HHSN27200013 (Co-PIs: FMM and EJA).Disclosures Molly Lamb, PhD, BioFire (Grant/Research Support) Evan J. Anderson, MD, Sanofi Pasteur (Scientific Research Study Investigator)