Safety and tolerance assessment of milk fat globule membrane-enriched infant formulas in healthy term Chinese infants: a randomised multicenter controlled trial

Abstract

Background: Milk fat globule membrane (MFGM), natural to breast milk, is essential for neonatal development, but lacking from standard infant formulas.

Objectives: To evaluate the safety and tolerability of MFGM supplementation in formula for infants 0 to 12 months.

Methods: In a prospective, multicentre, double-blind, randomized trial, healthy term infants were randomized to a standard formula (SF, n = 104) or an MFGM-enriched formula (MF, n = 108) for 6 months and a corresponding follow-on formula until 12 months. Exclusively breast-fed infants (n = 206) were recruited as the reference group (BFR). Tolerance and safety events were recorded continuously. Anthropometric measurements were assessed at enrolment, 42 days and 4, 6, 8 and 12 months.

Results: Infants (n = 375) completed the study with average dropout of < 20%. Stool frequency, color, and consistency between SF and MF were not significantly different throughout, except the incidence of loose stools in MF at 6 months being lower than for SF (odds ratio 0.216, P < 0.05) and the frequency of green-colored stools at 12 months being higher in MF (CI 95%, odds ratio 8.92, P < 0.05). The BFR had a higher frequency of golden stools and lower rate of green stools (4-6 months) than the two formula-fed groups (P < 0.05). SF displayed more diarrhoea (4.8%) than MF (1%) and BFR (1%) at the 8-month visit (P < 0.05). BFR (0-1%) had significantly less (P < 0.05) lower respiratory infections than MF (4.6-6.5%) and SF (2.9-5.8%) at 6- and 8-months, respectively. Formula intake, frequency of spit-up/vomiting or poor sleep were similar between SF and MF. Growth rate (g/day) was similar at 4, 6, 8 and 12 months between the 3 groups, but growth rate for BFR was significantly higher than for SF and MF at 42 days (95% CI, P = 0.001).

Conclusions: MFGM-enriched formula was safe and well-tolerated in healthy term infants between 0 and 12 months, and total incidences of adverse events were similar to that for the SF group. A few differences in formula tolerance were observed, however these differences were not in any way related to poor growth.

Keywords: Formula; Formula tolerance; Growth; Infant feeding; Milk fat globule membrane; Neurodevelopment.

Fig. 1

Flow chart of change in infant numbers in the MF, SF, and BFR groups during the study period and dropout reasons. MF, MFGM-enriched formula; SF, standard formula; BFR, breast-fed reference

Fig. 2

Mean (95% CI) of percentage milk intake (volume) of study formula in the MF (solid red line); and SF (dashed dot blue) and breast milk in BFR group (dashed blue line) at the postnatal age of 42 days, 4 months, 6 months, 8 months, and 12 months. MF: MFGM-enriched formula; SF: standard formula, BFR: breastfed reference

Fig. 3

Frequency (%) of different type of complementary food intakes at different age of infants who were introduced complementary food by parents/caregivers at 4 months (n = 24), 6 months (n = 321), 8 months (n = 354), 12 months (n = 356) respectively. MF: MFGM-enriched formula (black column); SF: standard formula (grey column), BFR: breastfed reference (white column)

Fig. 4

Comparison of incidence of stool colors, consistency and stool mucus presented as mean percentages of total occurrences in the MF group (black column) and SF group (grey column), and BFR group (white column) at the postnatal age of 42 days, 4 months, 6 months, 8 months, and 12 months. A. Frequency of stool colors between the groups. B. Frequency of stool consistency between the groups, C. Frequency of stool mucus between the groups. *p < 0.05, **P < 0.005. MF: MFGM-enriched formula; SF: standard formula; BFR: breast-fed reference

Fig. 5

Comparison of frequency of milk vomiting, no crying within 15 min after feeding and night crying presented as mean percentages of total occurrences in the MF group (black column), SF group (grey column) and the BFR group (white column) at the postnatal age of 42 days, 4 months, 6 months, 8 months, and 12 months. A. Frequency of milk vomiting between the group; B. Frequency of no crying within 15 min after feeding, C. Frequency of night crying between the groups. *p < 0.05, MF: MFGM-enriched formula; SF: standard formula; BFR: breast-fed reference

Fig. 6

Comparison of mean (± SD) of body weight (A), recumbent length (B), head circumference (C) and body mass index (D) from 0 to 12 months of age in MF (red line, n = 108), SF (green line, n = 104), and BFR (blue line, n = 206) groups. *p < 0.05. MF: MFGM-enriched formula; SF: standard formula; BFR: breast-fed reference; and BMI, body mass index