The timing and duration of a sensitive period in human flavor learning: a randomized trial

Abstract

Background: By using the response to protein hydrolysate formula (PHF) as a model system, we discovered the existence of a sensitive period, before 4 mo, when exposure determines the hedonic tone to flavors.

Objective: We aimed to characterize the timing and duration of this sensitive period.

Design: Healthy infants, whose parents had chosen formula feeding, were randomly assigned into 1 of 6 groups at age 0.5 mo: 2 control groups, one fed cow milk-based formula (CMF) and the other fed PHF for 7 mo; 2 groups fed PHF for either 1 or 3 mo beginning at 1.5 mo and CMF otherwise; and 2 groups fed PHF for 1 mo beginning at either 2.5 or 3.5 mo and CMF otherwise. Brief access taste tests were conducted monthly, and complete "meals" of both formulas occurred at the end of the study.

Results: Three months of PHF exposure led to acceptance similar to that at 1 mo of exposure. Although these infants were more accepting than were infants with no exposure, they were less accepting than were infants with 7 mo of exposure, which suggests a dosing effect. The time when flavor experiences began was also significant. Among infants exposed to PHF for 1 mo, those who were first fed PHF at 3.5 mo rejected PHF relative to CMF more than did infants exposed at younger ages.

Conclusion: The general principles observed are likely of broader significance, indicating a fundamental feature of mammalian development and reflecting the importance of familiarizing infants with flavors that their mothers consume and transmit to breast milk. This trial was registered at clinicaltrials.gov as NCT00994747.

FIGURE 1

Description of the control and treatment groups. The names of the groups refer to the duration [1 or 3 mo (1M or 3M)] and age (1.5, 2.5, or 3.5 mo) at which the infants were fed protein hydrolysate formula (PHF; dark gray boxes) or cow milk–based formula (CMF; light gray boxes). The months refer to the age of the infants at the beginning of each monthly cycle and then the age of the infants when the test meals were conducted. A brief-access, 2-bottle taste test (solid red vertical lines) was conducted at the end of each monthly cycle, and PHF and CMF test meals (dark trellis bars) were conducted at the end of the study (ie, 7.5 mo).

FIGURE 2

Mean (±SEM) amount of cow milk–based formula (CMF) and protein hydrolysate formula (PHF) consumed during the first brief-access, 2-bottle acceptance taste test in which infants were exposed to PHF at the beginning of the month (A) and then again after the first month of exposure (end of the month; B). The names of the groups refer to the duration [1 mo (1M)] and age (1.5, 2.5, or 3.5 mo) at which the infants were fed PHF: 1M1.5 (n = 11), 1M2.5 (n = 11), and 1M3.5 (n = 10). Although all 3 groups consumed significantly less PHF than CMF on their first day of exposure to PHF (P < 0.0001), the 1M3.5 group consumed significantly less PHF than did the other 2 groups (P < 0.05). By the end of the month, PHF acceptance had increased significantly (P < 0.0001) and was nearly as great as CMF acceptance (B). Although the end-of-month test indicated a significant main effect of formula (P = 0.04), none of the post hoc tests indicated significant differences in CMF and PHF intakes for any of the groups. Bars with different superscript letters are significantly different, P < 0.05.

FIGURE 3

Mean (±SEM) relative responses to protein hydrolysate formula (PHF/[PHF+cow milk–based formula (CMF)]) at the 7.5-mo test meals, based on the duration of exposure to PHF. Separate ANOVAs were conducted with a priori contrasts specified to determine whether 1 mo (1M1.5 group; n = 11), 3 mo (1M3.5 group; n = 11), and 7 mo (PHF Control; n = 12) of exposure differed from one another and whether these groups differed from the no-exposure control group (CMF Control; n = 13). Significant differences in relative intake (P < 0.001), maternal perceptions (P < 0.001), and rejection or distaste behaviors (P = 0.002) were observed. *Significantly different from the CMF Control, P < 0.0167. ^#Significantly different from the PHF Control, P < 0.0167. There were no significant differences between the 1M1.5 and 1M3.5 groups for any measure.

FIGURE 4

Mean (±SEM) relative responses to protein hydrolysate formula (PHF/[PHF+cow milk–based formula (CMF)]) at the 7.5-mo test meals, based on the timing of exposure to PHF. Separate ANOVAs were conducted with a priori contrasts to determine whether the 1-mo exposure groups [1M1.5 (n = 11), 1M2.5 (n = 11), and 1M3.5 (n = 11)] differed from the no-exposure control group (CMF control; n = 13). The names of the groups refer to the duration [1 mo (1M)] and age (1.5, 2.5, or 3.5 mo) at which the infants were fed PHF or to the control group who was fed CMF. Significant differences in relative intake (P = 0.02), maternal perceptions (P = 0.01), and rejection/distaste behaviors (P = 0.04) were observed. *Significantly different from the CMF Control, P < 0.0167. ^†Trend in differences from the CMF Control.

FIGURE 5

Infants' typical facial responses while consuming protein hydrolysate formula (PHF) when tested at 7.5 mo of age. A: Infant from the cow milk–based formula (CMF) control group (fed CMF for 7 mo). B: Infant from the PHF control group (fed PHF for 7 mo).