4. Discussion
SECONDARY
In this secondary analysis of a multicentre, randomised, controlled, double-blind trial, the GI tolerance of eHF was compared to that of CF. No significant differences were observed during the first 120 days of life, as reflected by similar stool characteristics, IGSQ and sleeping patterns.The daily number of stools decreased over time, with no significant differences between FF groups as previously shown elsewhere [The most commonly reported stool consistency of FF infants was soft, which is in line with previous findings with infant formulae manufactured from hydrolysed or intact protein containing pre- and/or probiotics [Overall, stool colour was comparable between FF groups. A yellow stool colour was dominant, but orange, brown, green, meconium, and clay-coloured stools were also noted. This wide variety of stool colours is common in healthy infants [Throughout the study period, median IGSQ scores were highly comparable between FF groups and were below proposed norm-reference values [Furthermore, there were no differences in sleeping characteristics between FF groups, with decreasing 24 h sleep and fewer sleep interruptions during the night as age increased. Rivkees et al. described a progressive maturation of the circadian system in infants [No statistical comparison to the non-randomised BF reference group was performed; thus, the following discussion is based on descriptive statistics only. In accordance with previous studies, exclusively breastfed infants have more frequent and softer stools than exclusively formula-fed infants [In the present study, GI tolerance assessed by the IGSQ questionnaire was comparable between the BF and FF groups, which may have contributed to the similar feeding amounts between these two groups, as already published [Notably, in the current study, approximately one third of all infants (FF and BF) received a medication or preparation, usually preventatively, aiming to improve GI tolerance and thereby potentially preventing some symptoms of intolerance that may have otherwise occurred in the study cohort. For this reason, post-hoc statistical analyses were performed. These revealed no differences in IGSQ total score between eHF and CF in the subgroup of infants who did not receive such products. According to these results, it can be assumed that the intake of the recorded products intended to improve GI tolerance had no measurable effect in this cohort. Even so, the relatively prevalent intake of products intended to improve GI tolerance is a limitation in this study.Furthermore, due to the nature of the trial design as a safety study, no data on infant microbiome are available, which may have provided further insight into GI tolerance.The presented evaluation of secondary outcome parameters is further limited in that the sample size calculation was based on the primary objective. Nevertheless, the high compliance and low dropout rate in this study together with the use of several validated tools resulted in comprehensive data on GI tolerance, stool characteristics, and sleeping patterns at multiple time points. Furthermore, the inclusion of a reference breastfed group allowed the descriptive comparison of infant formula tolerance to human milk as the ideal and recommended nutrient source for infants.