Infant feeding practice and gastrointestinal tolerance: a real-world, multi-country, cross-sectional observational study

Background Signs of feeding intolerance, such as gastrointestinal (GI) symptoms, are frequently observed in otherwise healthy formula-fed infants in the first months of life. The primary objective of this observational study was to examine GI tolerance in formula-fed infants (FFI) vs. breastfed infants (BFI) in a real-world setting with a secondary objective being the comparison of infants fed formula with pre- and/or probiotics (FFI_PP) and those fed formula without any pre- and/or probiotics (FFI_noPP) as well as BFI. Methods A six-country, cross-sectional study in full-term exclusively/predominantly FFI ( n = 2036) and BFI ( n = 760) aged 6–16 weeks was conducted using the validated Infant Gastrointestinal Symptom Questionnaire (IGSQ) and a Feeding Practice and Gut Comfort Questionnaire. Results The IGSQ composite score in FFI was non-inferior compared to BFI (mean difference [95%CI]: 0.17 [-0.34, 0.67]; non-inferiority p -value < 0.0001) and scores for BFI and FFI were below the threshold of 23, indicating no GI discomfort. Adjusted mean IGSQ scores ± SE were similar in FFI_PP (22.1 ± 0.2) and BFI (22.3 ± 0.3) while FFI_noPP (23.4 ± 0.3) was significantly higher and above 23 indicating some GI discomfort (mean differences [95%CI] FFI_noPP minus FFI_PP and FFI_noPP minus BFI were 1.28 [0.57, 1.98] and 1.09 [0.38, 1.80], respectively; both p < 0.01). Hard stools and difficulty in passing stool were more common in FFI compared to BFI ( p < 0.01) but were less common in FFI_PP compared to FFI_noPP ( p < 0.01). FFI_PP showed significantly less crying than FFI_noPP and was similar to BFI. Significantly fewer physician-confirmed colic episodes (Rome IV criteria) were reported in FFI_PP compared with FFI_noPP or BFI. Conclusions In this real-world observational study, FFI had non-inferior overall GI tolerance compared to BFI. Within FFI, infants receiving formulas with pre- and/or probiotics had a better GI tolerance, improved stooling and less infantile colic compared to those receiving formula without any pre- and/or probiotics and were more similar to BFI. Trial registration NCT03703583, 12/10/2018 ( https://clinicaltrials.gov/ct2/show/NCT03703583 ).