Infant nutritional status and markers of environmental enteric dysfunction are associated with mid‐childhood anthropometry and blood pressure in Tanzania
Authors: Locks Lindsey M , Mwiru Ramadhani S , Mtisi Expeditho , Manji Karim P , McDonald Christine M , Liu Enju , Kupka Roland , Kisenge Rodrick , Aboud Said , Gosselin Kerri , Gillman Mathew W , Gewirtz Andrew T , Fawzi Wafaie W , Duggan Christopher P 
Published: June 2021

BackgroundIn industrialized countries, risk factors for chronic diseases are linked with infant nutritional status; however, limited data exist from resource‐poor settings, where rates of undernutrition, infectious disease, environmental enteric dysfunction (EED), and impaired child growth in infancy and childhood are high.ObjectiveTo assess the extent to which growth and biomarkers of EED in infancy are related to health outcomes in mid‐childhood in Dar es Salaam, Tanzania.MethodsChildren who participated in one of two randomized controlled trials of micronutrient supplements in infancy were followed‐up in mid‐childhood (4.6–9.8 years). Anthropometry was measured at age 6 and 52 weeks in both trials, while blood samples were available from all children at 6 weeks and 6 months from one of the two trials. Linear regression models were used to assess whether length‐for‐age, weight‐for‐age and weight‐for‐length z‐scores (LAZ, WAZ and WLZ) at age 6 weeks, and change from 6 to 52 weeks, as well as flagellin IgG and IgA and LPS IgG and IgG predicted height‐for‐age, body‐mass‐index and weight for age z‐scores (HAZ, BMIZ and WAZ) as well as systolic and diastolic blood pressure in mid‐childhood.Results113 children were re‐enrolled in the follow‐up study in mid‐childhood. LAZ at 6 weeks and change in LAZ from 6 to 52 weeks were independent, positive predictors of HAZ in mid‐childhood in multivariate models (p<0.001 for both), while change in WAZ and WLZ from 6 to 52 weeks were also positively correlated with mid‐childhood HAZ in multivariate models. 6‐week WLZ and change in WLZ from 6 to 52 weeks were independently, positively associated with BMIZ in mid‐childhood in multivariate models as were WAZ at 6 weeks and change in WAZ during infancy. BMIZ in mid‐childhood was in turn positively associated with systolic blood pressure at follow‐up. Among the 66 children from the second trial who had blood samples analyzed for EED biomarkers, serum anti‐flagellin IgA concentration at 6 weeks was significantly associated with systolic and diastolic blood pressure in mid‐childhood in multivariate models (p=0.001 for both).ConclusionsLength at 6 weeks and gains in length in the first year of life are independently, positively associated with attained height in childhood, while weight at 6 weeks and weight gain throughout infancy are independently associated with an increased BMIZ in mid‐childhood. EED in infancy may also have long‐term consequences for cardio‐metabolic risk. Interventions in early life should focus on optimizing linear growth while minimizing excess weight gain and EED risk.Support or Funding InformationNational Institutes of Health (R01 HD043688‐01, R01 HD048969‐01, K24HD058795 and K24 DK104676), Bill and Melinda Gates Foundation (OPP1066203) and the Feed the Future Food Innovation Lab for Nutrition which is funded by the United States Agency for International Development (USAID).