**5. Conclusions**

In our study, five (11.6%) of the 43 children with DS were diagnosed with FPIES, and all cases were severe. The surgical history of colostomy and postoperative nutrition of formula milk feeding may have led to the onset of FPIES; furthermore, cases involving colostomy were the most severe ones in our study. Therefore, an amino acid-based formula should be considered for children who undergo gastrointestinal surgeries, especially colostomy in neonates or early infants. Serum IgE sensitization in infants with DS was low, as previously reported; thus, non-IgE-mediated food hypersensitivity disorder is more likely to occur in DS during infancy. When an acute gastrointestinal disease is suspected in children with DS, FPIES should be considered. This may prevent performing unnecessary tests and invasive treatments.

**Author Contributions:** Conceptualization, H.W., F.O., H.Y. and S.H.; methodology, F.O. and H.W.; software, F.O.; validation, H.W. and F.O.; formal analysis, F.O., H.W. and M.S.; investigation, F.O., H.W., Y.K, K.F. and K.T.; resources, F.O., H.W., Y.K., K.F., K.T. and M.S.; data curation, F.O., H.W., Y.K., K.T., K.F. and M.S.; writing—original draft preparation, F.O. and H.W.; writing—review and editing, S.H., F.O., H.W. and H.Y.; visualization, F.O. and H.W.; supervision, S.H., H.W. and H.Y.; project administration, H.W. and F.O. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by JSPS KAKENHI (Grant number, JP18K07848) (K.F.), a grant from the Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics (Grant number, 27-13) (S.H.), the Morinaga Foundation for Health & Nutrition (K.F.), and Grant-in-Aid for Translational Research of Yamaguchi University Hospital 2018 (S.H.).

**Institutional Review Board Statement:** The study was conducted in accordance with the Declaration of Helsinki. This study was approved by the Institutional Review Board of Yamaguchi University Hospital (H2020-198).

**Informed Consent Statement:** Informed consent was obtained from the parents of the patients.

**Data Availability Statement:** The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy.

**Acknowledgments:** We thank the patients, their families, and their friends for their cooperation.

**Conflicts of Interest:** The authors declare no conflict of interest.
