Gastrointestinal Factors Associated With Hospitalization in Infants With Cystic Fibrosis
Results From the Baby Observational and Nutrition Study
Sathe reports consulting for Alcresta Therapeutics and PBM BC Holdings, and research/grant support through the Cystic Fibrosis Foundation. Dr Leung reports received research/grant support from the Cystic Fibrosis Foundation, BMS, Gilead and Abbvie and service on the medical advisory board for Gilead and Merck. Dr Freeman reports research/grant support from the Cystic Fibrosis Foundation. Also of note, research reported in this publication was supported by Children's HealthSM. The content is solely the responsibility of the authors and does not necessarily represent the official views of Children's HealthSM.
BONUS and its lead investigators were supported by CFFT BONUS11KO, NIH R01DK095738, NIH P30DK089507, NIH R01DK095869, NIH K24HL141669, CFF SATHE18KO, CFFT SATHE18Y5, MISSION GRANT Children's HealthSM.
Author Contributions: Meghana Sathe: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Visualization, Writing - original draft, Writing – review & editing, and Final approval. Rong Huang: Formal analysis, Investigation, Methodology, Visualization, Writing – original draft, Writing – review & editing, and Final approval. Sonya Heltshe: Data curation, Formal analysis, Writing – review & editing, and Final approval. Alexander Eng: Data curation, Formal analysis, Investigation, Methodology, Writing – review & editing, and Final approval. Elhanan Borenstein: Formal analysis, Visualization, Writing – review & editing, and Final approval. Samuel I. Miller: Formal analysis, Visualization, Writing – review & editing, and Final approval. Lucas Hoffman: Formal analysis, Visualization, Writing – review & editing, and Final approval. Daniel Gelfond: Writing – review & editing and Final approval. Daniel H. Leung: Writing – review & editing and Final approval. Drucy Borowitz: Visualization, Writing – review & editing, and Final approval. Bonnie Ramsey: Visualization, Writing – review & editing, and Final approval. A. Jay Freeman: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Visualization, Writing – original draft, Writing – review & editing, and Final approval.
Trial Registration: United States ClinicalTrials.Gov registry NCT01424696 (clinicaltrials.gov).
ABSTRACT
Objectives:
To identify factors that increase the risk of gastrointestinal-related (GI-related) hospitalization of infants with cystic fibrosis (CF) during the first year of life.
Methods:
The Baby Observational and Nutrition Study was a longitudinal, observational cohort of 231 infants diagnosed with CF by newborn screening. We performed a post-hoc assessment of the frequency and indications for GI-related admissions during the first year of life.
Results:
Sixty-five participants had at least one admission in the first 12 months of life. High pancreatic enzyme replacement therapy (PERT) dosing (>2000 lipase units/kg per meal; hazard ratio [HR] = 14.75, P = 0.0005) and use of acid suppressive medications (HR = 4.94, P = 0.01) during the study period were positively associated with subsequent GI-related admissions. High levels of fecal calprotectin (fCP) (>200 μg/g) and higher relative abundance of fecal Klebsiella pneumoniae were also positively associated with subsequent GI-related admissions (HR = 2.64, P = 0.033 and HR = 4.49, P = 0.002, respectively). During the first 12 months of life, participants with any admission had lower weight-for-length z scores (WLZ) (P = 0.01). The impact of admission on WLZ was particularly evident in participants with a GI-related admission (P < 0.0001).
Conclusions:
Factors associated with a higher risk for GI-related admission during the first 12 months include high PERT dosing, exposure to acid suppressive medications, higher fCP levels, and/or relative abundance of fecal K pneumoniae early in life. Infants with CF requiring GI-related hospitalization had lower WLZ at 12 months of age than those not admitted as well as those admitted for non-GI-related indications.
