Serum Citrulline does not Predict Stunting or Environmental Enteric Dysfunction in Tanzanian and Malawian Infants

Background Serum citrulline (CIT) is a marker of gastrointestinal mucosal mass and function. Environmental enteric dysfunction (EED) is associated with suboptimal child growth, but robust biomarkers for EED are lacking. We sought to determine if CIT at age 6 weeks predicts stunting (height‐for‐age Z‐score < ‐2) at 18 months, and if CIT correlates with lactulose to mannitol (L:M) ratio, a measure of EED. Methods In 413 non‐stunted infants from Tanzania, blood was obtained at age 6 weeks, and anthropometrics measured monthly for 18 months. In 102 Malawian children between age 1‐3 years, dual‐sugar absorption tests were performed. CIT was analyzed in both studies by quadrupole mass spectrometer. Results In Tanzanian infants, mean (SD) CIT at 6 weeks was 18.0 (5.8) µmol/L. Compared to infants with CIT in the lowest quartile, the Hazard Ratio of time to first stunting for the highest quartile was 1.07 (95%CI: 0.64, 1.78). In Malawian children, mean (SD) CIT in stunted children was 18.2 (9.8) vs. 19.4 (9.5) in non‐stunted children (p=0.60). There was no association between L:M and CIT ( r =‐0.04, p=0.65) or height‐for‐age Z‐score and CIT ( r =‐0.10, p=0.31). Conclusion CIT did not predict subsequent stunting in Tanzania or correlate with markers of EED in Malawi. Biomarkers for adverse nutritional outcomes in children are needed. Funding NICHD (R01 HD048969; K24HD058795), Bill and Melinda Gates Foundation (OPP1066203)