Lower cognitive scores among toddlers in birth cohorts with acute respiratory illnesses, fevers, and laboratory‐confirmed influenza

Abstract

Background: We established cohorts to assess associations between viral influenza and cognitive development to inform the value proposition of vaccination. Methods: From 2014 through 2017, we called women seeking care at four prenatal clinics in Panama and El Salvador to identify acute respiratory illnesses (ARIs). Within 2 weeks of childbirth, mothers were asked to enroll their neonates in the cognitive development study. Staff obtained nasopharyngeal swabs from children with febrile ARIs for real-time reverse transcription polymerase chain reaction (rtPCR) detection of viral RNA. Toddlers were administered Bayley developmental tests at ages 12 and 18-24 months. We used multilevel linear regression to explore associations between Bayley scores, ARIs, fever, and laboratory-confirmed influenza, controlling for maternal respiratory or Zika illnesses, infant influenza vaccination, birth during influenza epidemics, and the number of children in households. Results: We enrolled 1567 neonates of which 68% (n = 1062) underwent developmental testing once and 40% (n = 623) twice. Children with previous ARIs scored an average of 3 points lower on their cognitive scores than children without ARIs (p = 0.001). Children with previous fevers scored an average of 2.1 points lower on their cognitive scores than afebrile children (p = 0.02). In the second year, children with previous laboratory-confirmed influenza scored 4 points lower on their cognitive scores than children without influenza (p = 0.04, after controlling for first Bayley cognitive scores).

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

“…Accumulating data from multinational cohorts suggest that neurodevelopment may have a related, but distinct causal pathway from stunting. 9,[30][31][32][33]36,37 Indeed, the aforementioned Bangladeshi cohort found that birth anthropometry and maternal weight were better predictors of growth, while clinical (fever) and biological markers of inflammation were more strongly associated with neurodevelopment. [5][6][7]9 Though not completely analogous to recurrent infections, mounting evidence suggests that human immunodeficiency virus (HIV)-infected, or even HIV-exposed, uninfected infants and children demonstrate neurodevelopment delays likely attributable to inflammation and immune dysregulation.…”

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

“…Accumulating data from multinational cohorts suggest that neurodevelopment may have a related, but distinct causal pathway from stunting. 9, 25-28, 31, 32 Indeed, the aforementioned Bangladeshi cohort found that birth anthropometry and maternal weight were better predictors of growth, while clinical (fever) and biological markers of inflammation were more strongly associated with neurodevelopment. 5-7, 9 Though not completely analogous to recurrent infections, mounting evidence suggests that human immunodeficiency virus (HIV)-infected, or even HIV-exposed, uninfected infants and children demonstrate neurodevelopment delays likely attributable to inflammation and immune dysregulation.…”

Immunity as key factors that influence cognitive development on children

“…When certain conditions are present, there is a link between certain infectious diseases, such as viral encephalitis, and cognitive deficits. 22 Children aged 12 months with acute respiratory illnesses (ARI) and fever had lower cognitive scores, according to the findings of a study conducted by Azziz-Baumgartner et al 23 It is possible, but not certain, that this finding was related to increased levels of pro-inflammatory interleukin during illness. 23 In addition to enteric infections and malnutrition in the first two years of life, enteric infections and malnutrition are linked to later cognitive impairment.…”

“…22 Children aged 12 months with acute respiratory illnesses (ARI) and fever had lower cognitive scores, according to the findings of a study conducted by Azziz-Baumgartner et al 23 It is possible, but not certain, that this finding was related to increased levels of pro-inflammatory interleukin during illness. 23 In addition to enteric infections and malnutrition in the first two years of life, enteric infections and malnutrition are linked to later cognitive impairment. A study evaluated the long-term effects of childhood diarrhea in the first two years of life by examining the cognitive function of Brazilian slum children.…”

“…16 Neurodevelopmental diseases, including schizophrenia, autism spectrum disorders, autismlike obsessive-compulsive behaviours and social impairment, are characterized by a disruption of a wide variety of processes in the developing brain that depend on the normal function of microglia. 15,[21][22][23][24] An amoeboid shape of microglia and higher cytokine production are both indicators that microglia in the brains of autistic and schizophrenia patients are in a more active state than microglia in the brains of healthy persons. 21 They are the product of a complicated interaction between inherited characteristics and the environment in which they were raised.…”