Environmental enteric dysfunction, systemic inflammation, growth hormones, and linear growth in infants in western Kenya: a prospective observational cohort study

Background: Environmental enteric dysfunction is associated with chronic systemic inflammation that results in growth hormone resistance and impaired growth although associations differ between settings. 

Objectives: We aimed to describe the time of onset and progression of intestinal pathology and explore associations between biomarkers of environmental enteric dysfunction, systemic inflammation, growth hormones, and linear growth in infants in western Kenya. 

Methods: In this prospective, observational cohort study, analysis is limited to infants recruited to the control arm (no intervention) of the PROSYNK trial between 28 October, 2020, and 13 January, 2022. Biomarkers of environmental enteric dysfunction, systemic inflammation, growth hormones, and infant length were measured at 6 wk and 3, 6, and 12 mo. Associations between biomarkers, growth hormones, and linear growth between time points were explored. 

Results: In 149 infants at age 6 wk, fecal myeloperoxidase (a biomarker of intestinal inflammation) was raised (≥0.2 mg/dL) in 47 of 143 (32.9%) and fecal α₁-antitrypsin (intestinal permeability; ≥26.8 mg/dL) in 26 of 142 (18.3%) infants. Chronic systemic inflammation (plasma α₁-acid glycoprotein, >1 g/dL) occurred from age 3 mo (33/140 infants; 23.6%). Once detected, intestinal inflammation, increased intestinal permeability, and chronic systemic inflammation persisted in most infants. Fecal myeloperoxidase, fecal α₁-antitrypsin, and plasma intestinal fatty acid–binding protein (intestinal integrity) were significantly positively associated with chronic systemic inflammation at some time points. Chronic systemic inflammation was significantly negatively associated with insulin-like growth factor 1 and insulin-like growth factor–binding protein 3 at 3, 6, and 12 mo. In multiple regression analysis, fecal α₁-antitrypsin at age 6 mo was negatively associated with subsequent change in length-for-age z-score (n = 124; coefficient: −0.32; 95% CI: −0.50, −0.13; P = 0.001). 

Conclusions: Targeting young infants with environmental enteric dysfunction, and especially increased gut permeability, may prevent or ameliorate chronic systemic inflammation and improve growth and development in infants in western Kenya. The PROSYNK trial was registered at the Pan African Clinical Trials Registry (https://pactr.samrc.ac.za/) as PACTR202003893276712 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9798).