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

Abstract

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 ).

Keywords: Crying time; Gastrointestinal tolerance; Infant formula; Infantile colic; Prebiotics; Probiotics; Stooling pattern.

Fig. 1

Adjusted mean IGSQ composite scores with SE as whiskers by feeding regimens.. Group comparison done by analysis of covariance adjusted for feeding regimen, study site, infant age, sex, delivery type, history of GI disease in parents, and mother’s education. IGSQ composite score can range from 13–65, with higher values indicating greater discomfort. Dotted line marks threshold of 23 indicating certain GI discomfort (> 23 to 30; > 30 to 65 indicates GI distress) and essentially no GI issues (≤ 23). BFI, Breastfed infants; FFI, Formula-fed infants; FFI_PP, formula fed infants with prebiotic and/or probiotic; FFI_noPP, formula fed infants with no prebiotic and/or probiotic; GI, gastrointestinal; IGSQ, Infant Gastrointestinal Symptom Questionnaire. n = 760 in BFI; n = 2036 in FFI; n = 1500 in FFI_PP; n = 501 in FFI_noPP. FFI_PP and FFI_noPP are subgroups of FFI. Thirty-five infants were not categorized into FFI_PP or FFI_noPP because of unknown formula composition

Fig. 2

Comparisons of stool characteristics between feeding groups. Comparisons of stool characteristics between the feeding groups are shown as rate ratios for stool frequency (2a), mean differences for stool consistency (2b), and odds ratios for difficulty passing stool (2c). The vertical line shows the reference value for each measure. Stool frequency and consistency and difficulty in passing stool were measured using the Feeding Practice and Gut Comfort Questionnaire, which collected number of stool and consistency for each stool in the 24 h prior to the administration of the questionnaire, as well as whether the infant had difficulty passing each stool. Stool consistency was measured using a 4-point scale (1 = Watery, 2 = Loose, 3= Formed, 4 = Hard). Stool frequency was modeled using negative binomial regression, consistency was modeled using ANCOVA, and difficulty passing stool was modeled using logistic regression. In addition to feeding regimen, models were further adjusted for study site, infant age, sex, delivery type, history of GI disease in parents, and mother’s education. BFI, Breastfed infants; CI, Confidence Interval; FFI, Formula-fed infants; FFI_PP, formula fed infants with prebiotic and/or probiotic; FFI_noPP, formula fed infants with no prebiotic and/or probiotic. n = 760 in BFI; n = 2036 in FFI; n = 1500 in FFI_PP; n = 501 in FFI_noPP. FFI_PP and FFI_noPP are subgroups of FFI. Thirty-five infants were not categorized into FFI_PP or FFI_noPP because of unknown formula composition

Fig. 3

Odds ratios with 95% confidence intervals comparing physician-confirmed colic between feeding groups. The vertical line shows reference value for the odds ratios. Physician-confirmed colic were measured using the Feeding Practice and Gut Comfort Questionnaire (“Was your child ever diagnosed colic?” and “Did the child have colic in the past week?”). Both outcomes were modeled using logistic regression and adjusted for study site, infant age, sex, delivery type, history of GI disease in parents, and mother’s education. BFI, Breastfed infants; CI, Confidence Interval; FFI, Formula-fed infants; FFI_PP, formula fed infants with prebiotic and/or probiotic; FFI_noPP, formula fed infants with no prebiotic and/or probiotic. n = 760 in BFI; n = 2036 in FFI; n = 1500 in FFI_PP; n = 501 in FFI_noPP. FFI_PP and FFI_noPP are subgroups of FFI. Thirty-five infants were not categorized into FFI_PP or FFI_noPP because of unknown formula composition