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Fetal Intestinal Cell Growth as a Measure of the Comparative Biofunctionality of Human Milk and Infant Formulas: An In Vitro Study.

BACKGROUND
Infant formulas are produced to resemble human milk (HM) and to provide adequate energy and appropriate nutritional components for suitability of infant growth and development, some of which are customized for specific medical conditions. However, it has remained unclear whether formulas contain any biofunctionality equivalent to HM, particularly fetal intestinal cell growth promotion.


OBJECTIVE
To evaluate the biofunctionality in HM and various formulas by using an in vitro fetal intestinal cell growth assay.


MATERIALS AND METHODS
Nine specimens of HM collected from 9 milk donors and 16 formulas consisting of 5 regular formulas (RFs), 2 preterm formulas (PFs), 2 partial hydrolysate formulas (PHFs), 3 extensive hydrolysate formulas (EHFs), 2 amino acid formulas (AAFs), and 2 soy protein formulas (SPFs) were included. Fetal intestinal cell growth assay was performed in six replicates per milk specimen. Biofunctionality of HM digest (HMD) derived from in vitro tryptic digestion of HM was also examined. Statistical analysis was performed by ANOVA with post-hoc Tukey's Honestly Significant Difference test.


RESULTS
The fetal intestinal cell growth-promoting activity of HM and formula groups were sorted from the highest as follows: HM, 192.8% ± 16.7%; AAF, 153.5% ± 17.8%; EHF, 149.4% ± 12.5%; RF, 123.5% ± 14.2%; PHF, 111.2% ± 17.9%; PF, 110.3% ± 8.2%; and SPF, 109.3% ± 17.3%. Statistical analysis showed that growth promotion of HM was significantly higher than that of all examined formulas (p < 0.0001). Among formulas, EHF and AAF showed greater growth-promoting activity than the others (p < 0.0001). HM and HMD had a comparable growth-promoting effect on fetal intestinal cells (198.5% ± 27.9% versus 191.2% ± 17.9%, p = 0.724), supporting the potential impact of HM biofunctionality under physiologic gastrointestinal digestion.


CONCLUSIONS
Our data suggested that formulas are not equivalent to HM in respect of fetal intestinal cell growth biofunctionality. Despite having less activity than HM, EHF and AAF exhibited considerable levels of growth-promoting effect that may have clinical implications, especially when HM is unavailable.