Sensitive Periods in Early Flavor Learning
Condition: Healthy
MeSH terms: Hypersensitivity
Study type: Interventional

Summary: 
      Flavor is the primary dimension by which young children determine food acceptance. However,
      children are not merely miniature adults since sensory systems mature postnatally and their
      responses to certain tastes differ markedly from adults. Moreover, emerging research has
      revealed that there are sensitive periods during infancy such that early flavor experiences
      serve to modify later responses to flavors and foods. The proposed study aims to investigate
      this important issue by using as a model system a class of infant formulas which are
      hydrolyzed protein based and thus have very pronounced and distinctive flavors which are
      unpalatable to older-aged infants and adults. This research was initiated because of
      anecdotal reports by pediatricians that although it is easy to introduce this type of formula
      to infants during the first months of life, it becomes extremely difficult to do so later in
      infancy. Indeed, recent studies in the investigators' laboratory provided the first
      experimental demonstration that infants younger than 4 months of age willingly accept
      substantial amounts of, and satiate while feeding, a novel, protein hydrolysate formula. In
      marked contrast, infants older than 4 months reject the protein hydrolysate formula and this
      rejection occurs within the first minute of a feed, a finding that strongly suggests the
      sensory qualities of the formula are responsible, at least in part, for this rejection.
      Moreover, this rejection is not evident when the investigators test older-aged infants with
      other unfamiliar, but non-hydrolysate, formulas. In other words, the rejection appears to be
      in response to a particular component or components of protein hydrolysate formulas. This
      shift in acceptability can be ameliorated by prior exposure. That is, if these formulas are
      introduced to infants within the first few months of life and are fed continuously, they
      remain highly acceptable throughout infancy and early childhood. These observations implicate
      a sensitive period during development, occurring somewhere before 4 months of age, during
      which exposure to a formula, which is unpalatable to adults and infants over 4 months of age
      without exposure, renders it acceptable and presumably palatable. To the investigators'
      knowledge, this is the clearest example of a sensitive period in the development of responses
      to foods and flavors in humans thus far identified.

      There is a paucity of information on whether and how the composition of formulas fed to
      infants influences their short-term feeding behaviors during the first few months of life.
      The primary objective of this longitudinal study is to determine the period during early
      infancy when exposure to the casein-hydrolysate formula, Nutramigen, renders it acceptable
      during later infancy. The study also aims to determine how early sensory experiences with
      formula impact upon food acceptance during infancy (8-9 months of age) and childhood. The
      investigators will also explore how variation in the genes that encode for taste receptors
      influence preferences for foods and other behaviors.
    

Detailed description: 
      This is a basic research, longitudinal and experimental study in which infants will be
      randomized into one of six groups (N=10-15 per group) differing in the timing and type of
      formula that the infant will be fed during each month of the 7-month exposure period. Each
      mother-infant dyad will be studied from the 2-3rd week of life until approximately 9 months
      of age. When the infant is less than three weeks of age and the mother's decision to formula
      feed is well established, infants will be randomized into one of six groups differing in the
      timing and type of formula that the infant will be fed during each month of the 7-month
      exposure period. One group (Control EEEEEEE) will be assigned to a milk-based formula,
      Enfamil (E), whereas another group (NNNNNNN) will be assigned to Nutramigen (N) during the
      entire 7-month period of this study. The other 4 groups will be assigned to feed Nutramigen
      for specified periods during their first seven months of life (Groups ENEEEEE, EEENEEE,
      ENNNEEE).

      A variety of methodologies developed in our laboratory will be employed to capture the
      infants' responses to a particular flavor or taste after the exposure period. That is, at the
      end of the exposure period, infants will be videotaped while they are 1) feeding formulas; 2)
      feeding foods (e.g., cereal; soups) that differ in flavors; and 3) exploring scented toys.
      Each month, infants will be weighed and measured for length as well as evaluated for
      cognitive and motor development and mothers will completed standardized questionnaires
      regarding infant temperament. A cheek swab from the mothers and infants will be obtained and
      genotyped for taste receptor and taste- and obesity- related genes.
    

Intervention name(s): Nutramigen (Flavor and Type of Infant Formula); Enfamil, milk-based formula
Intervention type(s): Other; Other
Intervention description(s): Nutramigen, protein hydrolysate formula, fed to infants as sole formula source during specified times during the first 8.5 months of life; Enfamil, milk-based formula, fed as formula source during first 8.5 months of life
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Basic Science
Keywords: infancy; nutrition; protein hydrolysate formula; flavor preferences; food preferences; growth; emotional development; mother-infant interaction; infant temperament; feeding patterning; taste receptor and obesity genotype; sensitive period