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Research

JAMA Pediatrics | Original Investigation

Capacity for Regulation of Energy Intake in Infancy


Lyndsey A. F. Reynolds, MD; Harlan McCaffery, MA; Danielle Appugliese, BA, MPH; Niko A. Kaciroti, PhD;
Alison L. Miller, PhD; Katherine L. Rosenblum, PhD; Ashley N. Gearhardt, PhD; Julie C. Lumeng, MD

Supplemental content
IMPORTANCE The capacity for regulation of energy intake (REI) to match energy needs is
thought to contribute to differences in weight gain, and preventing excess infant weight gain
is a priority.

OBJECTIVE To determine capacity for REI across infancy.

DESIGN, SETTING, AND PARTICIPANTS For this cohort study, a convenience sample of
mother-infant dyads was recruited from the community in Michigan between 2015 and 2019.
Inclusion criteria were healthy, full-term infants with weight appropriate for gestational age;
biological mothers who were 18 years or older, English speaking, and a legal and custodial
guardian; and infant having had consumed 2 oz or more in 1 feeding from an artificial nipple at
least once per week. Infants were followed in the home setting with staff support for up to
12 months.

INTERVENTIONS Mother-infant dyads participated at infant age 1, 2.5, 5, 7, 10, and 12 months.
In the intervention condition, mothers offered a feeding every hour for 6 hours. In the control
condition, mothers fed infants as they typically would for 6 hours. Intake was recorded and
kilocalories calculated.

MAIN OUTCOMES AND MEASURES Capacity for REI was indexed as the difference in intake in
kilocalories per kilogram of body weight (intervention minus control condition); a value of 0
indicated perfect REI. Maternal and infant characteristics were obtained by questionnaire,
and anthropometry was measured. Using multiple imputation, the intercept and slope for
difference in kilocalories per kilogram across the 6 age points were estimated using mixed
models accounting for repeated measures within participants. Statistical analyses were
conducted between September 2021 and February 2023.

RESULTS The sample included 175 infants (87 [49.71%] female, 88 [50.29%] male; 494 pairs
of intervention and control conditions and 4630 feedings). The mean (SD) 12-month
weight-for-age z score was 0.1 (0.8). Mean (SD) gestational age as 39.55 (1.05) weeks, and
mean (SD) birth weight was 3.43 (0.41) kg. Mean (SD) breastfeeding duration for those who
reported stopping by 12 months was 17.83 (12.03) weeks. As designed, the intervention
(compared with control) condition included more feedings at shorter intervals. After
collapsing the data across age points in a mixed model accounting for repeated measures
within participants, the REI estimate at 1 month differed from 0. On average, infants ate
5.21 kcal/kg (95% CI, 2.89-7.54 kcal/kg) more in the frequent feeding intervention condition
than in the ad lib feeding control condition. This difference did not significantly change over
12 months of infancy (REI slope = −0.01 kcal/kg per month; 95% CI, −0.02 to 0.03 kcal/kg per
month).

CONCLUSIONS AND RELEVANCE The study’s findings suggested that, on average, when offered
more frequent feedings, healthy, full-term infants may overeat. The results provide support
for responsive feeding as a strategy for preventing excess infant weight gain.

Author Affiliations: Author


affiliations are listed at the end of this
article.
Corresponding Author: Julie C.
Lumeng, MD, Division of
Developmental and Behavioral
Pediatrics, North Campus Research
Complex, Building 520, University of
JAMA Pediatr. 2023;177(6):590-598. doi:10.1001/jamapediatrics.2023.0688 Michigan, Ann Arbor, MI 48109
Published online April 17, 2023. (jlumeng@umich.edu).

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Capacity for Regulation of Energy Intake in Infancy Original Investigation Research

T
he capacity to regulate one’s intake—specifically, the
ability to upregulate or downregulate in response to Key Points
changes in caloric density or feeding frequency to match
Question Can healthy full-term infants accurately downregulate
energy needs—is thought to decline with age1-3 and to contrib- intake per feeding when offered feedings more frequently?
ute to differences in weight gain and obesity risk.2 Preventing
Findings In this cohort study of 175 mother-infant dyads and
excess weight gain in infancy and, later, obesity has been iden-
4630 feedings, eating behavior was interrogated by offering a
tified as a priority.4-6 The American Academy of Pediatrics
feeding every hour on 1 day and ad lib on another day for 6 hours.
states that physicians should identify infants who are gaining On average, infant intake increased by a statistically significant
weight rapidly and help to correct overfeeding, if present.7 In- amount (5.21 kcal/kg over 6 hours) when feedings were offered
fant appetite, such as higher food responsiveness and lower more frequently.
satiety responsiveness,8-10 and nonresponsive maternal feed-
Meaning The study’s findings suggested that, on average, infants
ing practices, such as using food to soothe,11-13 have been re- overeat when offered frequent feedings, providing support for
ported as potential risk factors. Expert panel guidelines have responsive feeding as a strategy for preventing excess infant
recommended, based on the results of several large, multi- weight gain.
component randomized controlled trials,4,14-17 that care-
givers use responsive feeding practices (eg, accurately recog-
nizing and responding to infant hunger cues) and avoid to determine the capacity for REI in response to more fre-
nonresponsive feeding practices (eg, pressuring the infant to quent feedings among healthy, full-term infants with re-
empty the bottle).18 The emphasis in the guidelines on avoid- peated measures across the first 12 months of infancy. On the
ing overfeeding is built on the hypothesis that infants will be basis of existing theories that nonresponsive feeding prac-
opportunistic feeders, ie, when given the opportunity to eat tices reduce infants’ ability to accurately recognize hunger and
more often, they will overeat. Indeed, when pediatric guide- satiation36,37 and prior literature suggesting that the capacity
lines transitioned in the 1950s from feeding infants on a sched- for REI declines after infancy,1-3 we hypothesized that infants
ule to feeding infants on demand, infants took more frequent would, on average, demonstrate a small but significant amount
feedings, took in more total daily volume, and gained more of overeating when offered the opportunity to feed more
weight.19-23 frequently.
Nonresponsive feeding in the form of offering feedings too
frequently could lead to excessive weight gain if the infant does
not respond by downregulating intake at each feeding. Al-
though there is relatively robust literature documenting in-
Methods
fants’ ability to downregulate intake in response to changes in This study used a repeated-measures, within-participant ex-
caloric density (eg, the classic work by Davis24,25 and Fomon perimental design embedded within a longitudinal observa-
and colleagues,26,27 as well as more recent work1,28,29), re- tional cohort study. The overall study sought to examine the
markably few studies have evaluated the capacity for regula- development of infant eating behavior longitudinally at ages
tion of energy intake (REI) in response to changes in feeding 1, 2.5, 5, 7, 10, and 12 months based on data collected from ques-
frequency. It is important to distinguish between these 2 types tionnaires, eating behavior experiments, and anthropometry
of challenges when interpreting prior literature, as there are via home visits by trained research staff.
likely different physiological mechanisms underlying each. Al-
though changing the caloric density of milk is a frequent in- Participants and Recruitment
tervention for preterm infants or malnourished children to in- A convenience sample of mother-infant dyads was recruited
crease weight gain, the caloric density of the diet is typically and enrolled from communities within a 1-hour driving dis-
not manipulated among healthy, full-term infants to prevent tance of Ann Arbor, Michigan, via social media; flyers in out-
excess weight gain. Being offered very frequent feedings is the patient pediatric clinics and community settings (eg, Women,
more common challenge to the capacity for REI among healthy, Infants, and Children offices); and targeted outreach by
full-term infants. telephone, email, and mail to pregnant women and mothers
Of the few studies in very early childhood that have ex- of newborn infants receiving care within the University of
amined the capacity for REI in response to more frequent feed- Michigan health system between October 2015 and February
ings, most have inferred a relatively good capacity for REI 2019. The planned sample size was based on a priori power cal-
through testing associations between meal frequency and meal culations for an analysis not presented in this report; the ul-
size using an observational cross-sectional cohort design.3,30-33 timate sample size was based on feasibility related to recruit-
Of these studies, only 1 included infants.3 The only studies that ment and retention.
we could identify that experimentally manipulated feeding fre- The study was described as seeking to understand infant
quency involved infants in the neonatal intensive care unit and eating behavior and interactions between mothers and ba-
evaluated time to attainment of full oral feedings and not ca- bies in the first year after birth. Inclusion criteria were gesta-
pacity for REI.34,35 We also have been unable to identify any tional age of 37.0 to 42.0 weeks, weight appropriate for ges-
studies that have examined development of the capacity for tational age, no significant perinatal or neonatal complications,
REI across infancy in response to changes in feeding fre- biological mother was the legal and custodial guardian, and
quency. Therefore, in this study, we used a novel experiment infant’s having had consumed 2 oz or more in 1 feeding from

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Research Original Investigation Capacity for Regulation of Energy Intake in Infancy

in the analytic sample if the paired intervention and control


Figure 1. Participant Flow Diagram
conditions were implemented with fidelity for at least 1 age
336 Mother-infant dyads assessed
point (Figure 1). The 175 infants included in the analytic sample
for eligibility did not differ from the 109 infants excluded across any of the
tested characteristics (eTable 1 in Supplement 1). The sample
52 Dyads did not meet eligibility criteriaa
of infants did not differ in any of the tested characteristics based
10 Gestational age <37.0 wk
22 Birth weight not appropriate for gestational age on enrollment age (eTable 2 in Supplement 1) or the number
10 Infant with substantial perinatal or medical of age points in which the infant participated (eTable 3 in
problems
5 Infant did not take or mother did not intend to offer Supplement 1) with the exception that infants of mothers who
infant 2 oz from a bottle before enrollment window were married participated in more age points.
1 Mother not fluent in English
3 Mother aged <18 y
21 Did not participate in first visit Capacity for REI
Dyads were invited to participate at every age point (ie, 1, 2.5, 5,
284 Dyads enrolled
7, 10, and 12 months) in an experiment developed for this study
to assess the infant’s capacity for REI in response to more fre-
74 Dyads did not participate in any intervention
or control condition at any age point quent feedings. Mothers completed the experiment at home with
remote support from research staff as needed. Mothers and re-
210 Dyads participated in ≥1 intervention search staff were blind to the study hypotheses. The mother was
or control condition at ≥1 age point
(1321 intervention or control conditions) asked to feed as she typically would for 6 hours on 1 day (con-
trol condition) and, on a separate day within 1 week, to offer a
155 Intervention or control conditions not implemented feeding every hour for 6 hours (intervention condition). The in-
with fidelity (11 dyads)a tervention and control conditions were identical with the ex-
124 Solid food intake not recorded with sufficient
precision to allow calculation of kilocalories ception of feeding frequency. By design, the intervention con-
48 Data recording error (ie, missing feeding times) dition always followed the control condition on the premise that
37 Intervention condition time between feedings
>1.5 h the risk of the intervention condition affecting the control con-
36 Intervention condition duration too short dition would be much greater than the risk of the control con-
17 Either condition initiated between 9 PM and 4 AM
2 No intake during control condition dition affecting the intervention condition if done in that order.
Furthermore, an extended washout period would have in-
199 Dyads participated in ≥1 intervention creased participant burden and reduced our ability to compare
or control condition implemented with
fidelity at ≥1 age point (1166
the paired conditions at a specific age point during the rapid de-
intervention or control conditions) velopment that characterizes infancy.
For milk feedings, mothers fed the infant their usual milk
178 Matched intervention-control condition pairs not with their usual bottle and artificial nipple. Bottles contained
implemented with fidelity (24 dyads)
150 Only 1 condition implemented with fidelity 1 additional ounce of milk than typical to ensure that intake
23 Number of feedings offered in intervention was not artificially constrained. Mothers were asked to termi-
condition was not greater than number of
feedings offered in control condition nate feedings as they typically would; bottles were covered with
3 Start times between paired conditions differed
by >6 h
cloth to limit the impact of visual assessment on feeding ter-
2 Data submitted in duplicate at 2 age points mination. Mothers recorded the milk type (breast milk vs for-
mula) and amount consumed using bottle weights before and
175 Dyads analyzed (494 matched after feeding (precision of ±0.5 g, TE32FT Digital Scale; Taylor
intervention-control condition
pairs; 4630 feedings) Precision Products Inc). During the intervention condition,
mothers were instructed to gently brush the nipple across the
a
May be more than 1 reason. lips of sleepy or sleeping infants, but not to purposefully
awaken the infant. Energy intake was estimated as 20 kcal per
30 g of milk.
an artificial nipple at least once per week. Exclusion criteria Mothers reported intake during complementary feedings by
were mother not fluent in English; mother younger than 18 completing a food record immediately after each feeding that
years; infant medical problems or diagnosis affecting current prompted them to record the food type, ingredients, brand, and
or future eating, growth, or development; or child protective amount consumed. Estimated food records have been
services involvement. Mothers provided written informed con- validated against 24-hour dietary recalls,38 weighted food
sent for themselves and their infants. The study was ap- records,39 and blood biomarkers of dietary intake.40 From these
proved by the University of Michigan institutional review data, 2 research assistants estimated kilocalories based on pack-
board. The study followed the Strengthening the Reporting of age labeling and standard references. If estimates differed by
Observational Studies in Epidemiology (STROBE) reporting more than 20%, a third researcher made a final determination.
guideline. Milk and complementary feeding kilocalories were
To facilitate recruitment, dyads could be enrolled at 1 of 3 summed. Capacity for REI was calculated as difference in in-
age points up to and including age 5 months; data collected at take per kilogram of infant body weight (ie, difference in ki-
enrollment are referred to as baseline. Infants were included localories per kilogram consumed between the intervention

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Capacity for Regulation of Energy Intake in Infancy Original Investigation Research

and control conditions). A value of 0 indicated perfect REI.


Table 1. Sample Characteristics
Mothers recorded start time and any spit-ups for each feed-
ing. If mothers wished to have someone else (eg, the father) Characteristic No. (%)
do some of the feedings, she was able to do so but were asked No. of infants 175

to continue to adhere to the study instructions and to record Infant sex


the identity of the feeder. Conditions that were not imple- Female 87 (49.71)
mented by the feeder with full fidelity to the instructions given Male 88 (50.29)
were excluded from the analysis (Figure 1). Infant race and ethnicity
Black, non-Hispanic 26 (15.03)
Demographic Characteristics and Anthropometry Hispanic, any race 10 (5.78)
Mothers reported infant sex, gestational age, and birth weight; White, non-Hispanic 108 (62.43)
their own age and education level; and family structure and Othera 29 (16.76)
household income and size. We collected mother-reported in- Gestational age, mean (SD), wk 39.55 (1.05)
fant and maternal race and ethnicity for descriptive pur- Birth weight, mean (SD), kg 3.43 (0.41)
poses; response options were those used by the National Breastfeeding duration, mean (SD), wk 17.83 (12.03)
Institutes of Health (ie, American Indian or Alaska Native, Maternal race and ethnicity
Asian, Black or African American, Hispanic or Latino, Native Black, non-Hispanic 27 (15.61)
Hawaiian or Pacific Islander, White, multiracial, and other).41
Hispanic, any race 5 (2.89)
Income to needs ratio was calculated by dividing income by
White, non-Hispanic 121 (69.94)
the poverty income threshold for a household of a given size.
Othera 20 (11.56)
Mothers reported on breastfeeding at each age point, from
Maternal age, mean (SD), y 31.15 (4.96)
which breastfeeding duration was calculated. Mothers also re-
Maternal education
ported the number of feedings per week that were provided
High school diploma or less or GED 16 (9.14)
from the breast vs a bottle, from which the proportion of feed-
Some college 46 (26.29)
ings that were bottle fed in the usual diet was calculated.
4-y College degree 54 (30.86)
Infants were weighed without clothing or a diaper on a
BD-585 Digital Infant Scale (Tanita) in duplicate, and weights >4-y College degree 59 (33.71)

were averaged. If the weights differed by more than 0.1 kg, a Family structure

third weight was obtained. Recumbent length was measured Single, never married 17 (10.12)
in duplicate to the nearest 0.1 cm using standardized Married 126 (75.00)
approaches42 with a pediatric stadiometer (M-PED LB 35- In a committed relationship 20 (11.90)
107-X; Ellard Instruments), and lengths were averaged. If mea- Separated or divorced 5 (2.98)
surements differed by more than 0.2 cm, a third measure- Income to needs ratio, mean (SD) 3.36 (2.26)
ment was obtained. Anthropometry was completed by trained Identity of feeder
research staff who were recertified annually in measurement Mother for every feeding at every age point 58 (35.37)
techniques. Weight-for-age z score, length-for-age z score, and Other than mother for at least 1 feeding 106 (64.63)
weight-for-length z score were calculated based on World at any age point

Health Organization growth charts.43 Abbreviation: GED, General Educational Development test.
a
Other includes Asian, multiracial, or other race, non-Hispanic.
Statistical Analysis
Between September 2021 and February 2023, data analysis was Multiple imputation was done to impute missing out-
performed using SAS, version 9.4 (SAS Institute Inc) and R, ver- come data (capacity for REI) using variables known to be as-
sion 4.0.5 (R Foundation for Statistical Computing) statistical sociated with infant eating and growth in the existing litera-
software. Univariable statistics were used to describe the ture (infant sex,44 infant race and ethnicity,45 gestational age,30
sample. Bivariate analyses accounting for repeated measures and birth weight44). Using 100 imputations, the intercept and
within participants were conducted using mixed models with slope for difference in kilocalories per kilogram between con-
a random intercept to evaluate differences between the inter- ditions across the 6 age points were estimated using mixed
vention and control conditions at each age point. models accounting for repeated measures within partici-
In mixed multilevel models with repeated measures across pants (proc mixed in SAS). The t test and the corresponding P
age points, none of the following characteristics of the inter- value for each fixed effect were derived while following the
vention and control conditions were associated with differ- Rubin rule46 to account for the uncertainty across 100 impu-
ence in kilocalories per kilogram between conditions and were tations. The threshold for significance was set at a 2-sided
therefore not further considered in analyses: difference in start P < .05.
time between conditions, complementary feedings (solids)
were ever offered, breast milk was ever offered, the infant ever
spit up, the feeder was ever someone other than the mother,
and the proportion of feedings that were bottle fed in the usual
Results
diet. Characteristics of the sample are shown in Table 1. The co-

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Research Original Investigation Capacity for Regulation of Energy Intake in Infancy

hort included 175 infants (female, 87 [49.71%]; male, 88 parisons. This finding is significant given that it has been well
[50.29%]; Black, 26 [15.03%]; Hispanic, 10 [5.78%]; White, 108 established that weight gain results from small daily energy
[62.43%]; other race and ethnicity, 29 [16.76%]), 494 pairs of imbalances over time.47 Our findings differ from several stud-
intervention and control conditions, and 4630 feedings. The ies among infants and toddlers that did not involve an experi-
mean (SD) 12-month weight-for-age z score was 0.1 (0.8). Mean mental design but inferred good capacity for REI through di-
(SD) gestational age was 39.55 (1.05) weeks, and mean (SD) birth etary record analysis, which showed relatively constant daily
weight was 3.43 (0.41) kg. Mean (SD) breastfeeding duration energy intake despite varying meal size.3,30-33 Our results sup-
for those who reported stopping by 12 months was 17.83 (12.03) port recommending responsive feeding to prevent excess
weeks. Mean (SD) maternal age was 31.15 (4.96) years, 113 moth- weight gain.14-16,18 We did not find evidence that the capacity
ers (64.57%) had a 4-year college degree or more, and 126 for accurate REI changed across the first 12 months of in-
(75.00%) were married. Mean (SD) family income to needs ra- fancy. Several studies have found that the ability to regulate
tio was 3.36 (2.26), with 48 families (30.57%) having an in- intake begins to diminish after infancy.1-3 Our findings in com-
come to needs ratio below 1.85 (low income). The mother was bination with this literature suggest that early childhood de-
the only feeder for every feeding at every age point for 58 in- clines in the capacity for REI may begin after age 12 months.
fants (35.37%). Whether the infant was offered complementary foods (sol-
Table 2 shows characteristics of the sample of infants and ids) or formula vs breast milk during the intervention or con-
intervention and control conditions at each age point. The com- trol conditions was not associated with the infant’s capacity
position of the sample with regard to infant sex, infant race and for REI; nor was the proportion of feedings that were bottle fed
ethnicity, and income to needs ratio at enrollment did not dif- in the infant’s typical diet. These results align with studies that
fer significantly across the 6 age points. In unadjusted bivar- found no difference in food responsiveness or likelihood of
iate comparisons accounting for repeated measures within par- emptying the bottle based on whether the bottle contained
ticipants at each age and correcting for multiple comparisons, breast milk or formula48,49 but differ from literature report-
the intervention and control conditions demonstrated the in- ing associations between breastfeeding and better capacity for
tended differences as designed. Specifically, the intervention REI.48,50,51 The associations of breastfeeding and complemen-
(compared with control) condition included more feedings at tary feeding with the development of REI are important areas
shorter intervals. There were no differences in start time, with for future work.
1 exception: on average, infants at the 1-month age point started
the intervention condition approximately 1 hour earlier. There Strengths and Limitations
were no differences in whether solids or breast milk were of- Strengths of this study include the large, longitudinal sample
fered, the infant ever spit up, or the feeder was ever not the with objective measures of infant capacity for REI. The study
mother. Test results for each age point separately and cor- also had several limitations. First, the findings may not be gen-
rected for multiple comparisons showed that the capacity for eralizable to infants dissimilar to this cohort. Second, infants
REI did not differ significantly from 0 at any age point. entered the study at different ages, and there was attrition, but
A spaghetti plot of the observed data across infancy with the sample did not differ based on data completeness. Third,
a locally estimated scatterplot smoothing curve is shown in the study required that infants be capable bottle feeders, which
Figure 2. Collapsing the data across age points in a mixed model limits generalizability to infants who are exclusively fed from
accounting for repeated measures within participants showed the breast (who represent a small minority of infants52,53).
that the REI estimate at 1 month differed from 0. On average, Fourth, while home data collection contributed to some de-
infants ate 5.21 kcal/kg (95% CI, 2.89-7.54 kcal/kg) more in the gree of error and resulting data loss, our approach increased
frequent feeding intervention condition than in the ad lib feed- ecologic validity and feasibility. Fifth, the intervention and con-
ing control condition. This difference did not significantly trol conditions were each limited to 6 hours on each day be-
change over 12 months of infancy (−0.01 kcal/kg per month; cause offering a feeding every hour for a longer duration may
95% CI, −0.02 to 0.03 kcal/kg per month). have been unsafe for infants less able to downregulate. Sixth,
although biological rhythms that mature over the first 6 months
are known to contribute to appetite,54 requiring a specific start
time was not feasible, and start time did not alter the results
Discussion in our analyses. Seventh, although consistently administer-
To our knowledge, this study is the first to objectively mea- ing the control condition before the intervention condition pro-
sure infant capacity for REI in response to increased feeding vided many benefits, normal physiologic growth in the days
frequency using an experimental design in healthy, full-term between conditions is associated with increases in caloric
infants longitudinally across the first 12 months of infancy. needs. However, the magnitude of increase in the interven-
Across more than 4000 feedings among 175 infants, we found tion condition substantially exceeded the estimated physi-
that when given the opportunity to feed more frequently over ologic increase in caloric intake that would be expected, even
6 hours, infants increased their intake on average by approxi- during the most rapid period of infant growth. Eighth, al-
mately 5 kcal/kg body weight. This difference was detectable though it is possible that mothers could have intentionally ma-
when the data were combined across all age points, which pro- nipulated the amount the infant consumed (ie, discouraging
vides greater power than examining each age point sepa- feeding) during the intervention condition to purposefully
rately and with conservative adjustment for multiple com- match intake in the control condition, the fact that mothers

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Capacity for Regulation of Energy Intake in Infancy Original Investigation Research

Table 2. Characteristics of Infants and of Intervention and Control Conditions Across 6 Age Pointsa

Age points, mo, No. (%)


Characteristic 1 2.5 5 7 10 12
Infants
No. of infants 52 108 107 107 72 48
Age, mean (SD), mo 0.99 (0.33) 2.46 (0.47) 4.58 (0.56) 6.55 (0.47) 9.61 (0.44) 12.53 (0.71)
Sex
Female 23 (44.23) 64 (59.26) 55 (51.40) 55 (51.40) 37 (51.39) 28 (58.33)
Male 29 (55.77) 44 (40.74) 52 (48.60) 52 (48.60) 35 (48.61) 20 (41.67)
Infant race and ethnicity
Black, non-Hispanic 4 (7.69) 15 (14.02) 13 (12.15) 13 (12.38) 10 (13.89) 4 (8.33)
Hispanic, any race 3 (5.77) 5 (4.67) 6 (5.61) 7 (6.67) 7 (9.72) 3 (6.25)
White, non-Hispanic 35 (67.31) 74 (69.16) 64 (59.81) 64 (60.95) 47 (65.28) 30 (62.50)
Otherb 10 (19.23) 13 (12.15) 24 (22.43) 21 (20.00) 8 (11.11) 11 (22.92)
Income to needs ratio at 4.12 (2.44) 3.32 (2.16) 3.40 (2.19) 3.34 (2.21) 3.54 (2.30) 3.70 (1.92)
baseline, mean (SD)
z Score, mean (SD)
Weight for age −0.10 (0.93) −0.23 (1.00) 0.00 (0.95) −0.02 (0.96) 0.11 (0.92) 0.13 (0.82)
Length for age −0.16 (0.87) −0.02 (0.89) −0.11 (1.00) −0.38 (0.99) −0.41 (1.10) −0.25 (0.99)
Weight for length −0.19 (1.00) −0.01 (1.02) 0.16 (0.95) 0.39 (0.90) 0.49 (0.88) 0.35 (0.77)
Proportion of feedings bottle 52.47 (39.07) 52.41 (40.97) 58.90 (42.13) 64.27 (40.83) 72.33 (38.6) 81.30 (33.46)
fed in usual diet
Control condition
Mean feeding interval, mean 2.40 (1.06) 2.58 (1.05) 2.59 (0.92) 2.59 (1.10) 2.26 (0.99) 2.48 (1.45)
(SD), h
No. of feedings, mean (SD) 3.15 (1.16) 2.94 (1.01) 2.99 (0.93) 3.07 (1.03) 3.22 (1.05) 3.00 (1.13)
Start time, mean (SD), h:minc 11:35 (2.73) 11:33 (3.11) 11:29 (3.21) 10:33 (2.67) 10:12 (2.82) 10:01 (2.93)
Any solids 0 (0.00) 6 (5.56) 16 (14.95) 52 (48.60) 50 (69.44) 33 (68.75)
Any breast milk 28 (53.85) 62 (57.41) 58 (54.21) 50 (46.73) 27 (37.50) 11 (22.92)
Infant ever spit up 11 (21.57) 22 (20.37) 19 (17.92) 10 (9.35) 0 (0.00) 1 (2.13)
Feeder ever not mother 12 (37.50) 35 (38.89) 34 (36.96) 44 (43.56) 25 (34.72) 14 (29.79)
Intake across 6 h, mean (SD),
kcal
Milk 166.87 (61.89) 195.11 (83.42) 229.50 (98.00) 234.79 (103.66) 231.47 (132.95) 189.91 (110.42)
Solids 0.00 (0.00) 1.02 (6.14) 8.32 (32.25) 28.48 (49.47) 70.39 (74.92) 145.73 (149.30)
Total 166.87 (61.89) 196.13 (84.05) 237.82 (106.95) 263.28 (109.40) 301.86 (144.43) 355.64 (171.53)
Total intake, mean (SD), kcal/kg 44.23 (16.92) 37.79 (17.12) 34.70 (16.73) 34.17 (14.46) 34.87 (17.43) 35.31 (17.78)
Intervention condition
Mean feeding interval, mean 0.98 (0.08) 1.00 (0.10) 1.00 (0.09) 0.99 (0.08) 0.99 (0.09) 0.99 (0.08)
(SD), h
No. of feedings, mean (SD) 6.29 (0.96) 6.29 (0.87) 6.26 (0.70) 6.37 (0.68) 6.38 (0.72) 6.40 (0.71)
Start time, mean (SD), h:minc 10:37 (2.27) 10:47 (2.91) 10:43 (2.91) 10:14 (2.78) 9:35 (2.69) 9:45 (2.65)
Any solids 0 (0.00) 5 (4.63) 17 (15.89) 46 (42.99) 46 (63.89) 35 (72.92)
Any breast milk 28 (53.85) 61 (56.48) 57 (53.27) 48 (44.86) 24 (33.33) 10 (20.83)
Infant ever spit up 11 (21.57) 28 (26.17) 23 (22.33) 16 (15.38) 5 (7.14) 3 (6.25)
Feeder ever not mother 6 (18.18) 36 (39.56) 39 (42.86) 41 (40.59) 24 (33.33) 16 (33.33)
Intake across 6 h, mean (SD),
kcal
Milk 190.54 (78.46) 213.21 (93.55) 250.51 (106.19) 263.45 (141.53) 281.84 (168.77) 241.70 (134.19)
Solids 0.00 (0.00) 1.25 (9.69) 8.06 (26.82) 20.73 (45.38) 65.28 (82.58) 119.88 (145.72)
Total 190.54 (78.46) 214.47 (94.15) 258.56 (108.04) 284.19 (146.80) 347.12 (176.60) 361.57 (181.50)
Total intake, mean (SD), kcal/kg 51.62 (23.16) 41.56 (19.23) 37.81 (17.06) 37.43 (20.70) 40.06 (20.91) 37.29 (18.36)

(continued)

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Research Original Investigation Capacity for Regulation of Energy Intake in Infancy

Table 2. Characteristics of Infants and of Intervention and Control Conditions Across 6 Age Pointsa (continued)

Age points, mo, No. (%)


Characteristic 1 2.5 5 7 10 12
Difference between intervention and control conditions, point estimate (95% CI)d
Mean feeding interval, h −1.42 (−1.81 to −1.59 (−1.85 to −1.58 (−1.82 to −1.60 (−1.88 to −1.27 (−1.58 to −1.49 (−2.05 to
−1.03) −1.33) −1.34) −1.32) −0.96) −0.93)
Total No. of feedings 3.13 (2.74 to 3.52) 3.35 (3.08 to 3.62) 3.27 (3.02 to 3.52) 3.30 (3.03 to 3.15 (2.83 to 3.40 (2.94 to 3.86)
3.57) 3.47)
Start time, min −58.20 (−113.01 −45.50 (−106.76 −45.77 (−107.41 −19.20 (−58.75 to −36.60 (−97.78 to −15.60 (−88.19 to
to −3.39) to 15.76) to 15.87) 20.35) 24.58) 56.99)
Any solid food (%) NAe −0.93 (−6.38 to 0.94 (−6.57 to −5.61 (−18.14 to −5.55 (−19.22 to 4.17 (−13.28 to
4.52) 4.52) 6.92) 8.12) 21.62)
Any breast milk (%) NAe −0.93 (−3.38 to −0.94 (−3.42 to −1.87 (−5.32 to −4.17 (−10.38 to −2.09 (−7.54 to
1.52) 1.54) 1.58) 2.04) 3.36)
Infant ever spit up (%) 0.00 (−0.21 to 5.8 (−5.87 to 4.41 (−6.16 to 6.03 (−2.52 to NAe 4.12 (−7.43 to
0.21) 17.47) 14.98) 14.58) 15.67)
Feeder ever not mother (%) −19.32 (−42.06 to 0.67 (−9.70 to 5.9 (−4.54 to −2.97 (−16.95 to −1.39 (−15.48 to 3.54 (−10.39 to
3.42) 11.06) 16.34) 11.01) 12.70) 17.47)
Total intake across 6 h, kcal 23.67 (−2.57 to 18.34 (−2.93 to 20.74 (−5.27 to 20.91 (−9.06 to 45.26 (−7.78 to 25.93 (−53.68 to
49.91) 39.61) 46.75) 50.88) 98.30) 105.54)
Total intake across 6 h, kcal/kg 7.38 (−0.05 to 3.77 (−0.32 to 3.11 (−0.98 to 3.27 (−0.91 to 5.18 (−1.03 to 1.97 (−6.75 to
14.81) 7.86) 7.20) 7.45) 11.39) 10.69)
c
Abbreviation: NA, not applicable. SD for time is shown in minutes.
a d
No. of infants, 175; 494 matched pairs of intervention and control conditions; The 95% CIs are adjusted for multiple comparisons.
4630 feedings. e
Due to low frequency of characteristic.
b
Other includes Asian, multiracial, or other race, non-Hispanic.

jectively measured, and complementary feedings were mea-


Figure 2. Difference Between Intervention and Control Conditions in
Infant Capacity for Regulation of Energy Intake to Age 12 Months With
sured less objectively.33
Locally Estimated Scatterplot Smoothing Curve

100

80
Conclusions
The results of this cohort study provide evidence that, on av-
Total intake across 6 hours, kcal/kg

60
erage, infants may overeat when fed too frequently. Cumula-
40
tive effects may contribute to excess weight gain. Future work
20
should consider correlates and predictors of REI, which might
0 include infant feeding practices, temperament, appetitive
-20 traits, sleep, biological features of the intrauterine environ-
ment, epigenetic or genetic factors, or the microbiome.
-40
On average, infants have an imperfect capacity for REI
-60
when fed frequently. The study’s findings reinforce the value
-80 of responsive feeding and avoiding using food as a soothing
0 2 4 6 8 10 12 14
Infant age, mo strategy.18 Furthermore, the American Academy of Pediatrics
recommends establishing feeding routines55-57 and occasion-
ally offering water to infants wanting to feed excessively.55,56
were blind to the study hypotheses mitigates this concern. Ongoing refinement of interventions that support responsive
Ninth, the caloric density of breast milk varies but was not ob- feeding is an important area for future work.

ARTICLE INFORMATION (Appugliese); Department of Biostatistics, Author Contributions: Dr Lumeng had full access
Accepted for Publication: February 24, 2023. University of Michigan School of Public Health, Ann to all of the data in the study and takes
Arbor, Michigan (Kaciroti); Department of Health responsibility for the integrity of the data and the
Published Online: April 17, 2023. Behavior and Health Education, University of accuracy of the data analysis.
doi:10.1001/jamapediatrics.2023.0688 Michigan School of Public Health, Ann Arbor, Concept and design: Miller, Rosenblum, Gearhardt,
Author Affiliations: Division of Pediatric Michigan (Miller); Department of Psychiatry, Lumeng.
Endocrinology, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Acquisition, analysis, or interpretation of data:
University of Michigan, Ann Arbor, Michigan Michigan (Rosenblum); Department of Psychology, Reynolds, McCaffery, Appugliese, Kaciroti, Miller,
(Reynolds); Division of Developmental and University of Michigan, Ann Arbor, Michigan Rosenblum, Lumeng.
Behavioral Pediatrics, Department of Pediatrics, (Gearhardt); Department of Nutritional Sciences, Drafting of the manuscript: Reynolds, Appugliese,
University of Michigan, Ann Arbor, Michigan University of Michigan School of Public Health, Ann Lumeng.
(McCaffery, Lumeng); Appugliese Professional Arbor, Michigan (Lumeng). Critical revision of the manuscript for important
Advisors, North Easton, Massachusetts intellectual content: McCaffery, Kaciroti, Miller,

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Capacity for Regulation of Energy Intake in Infancy Original Investigation Research

Rosenblum, Gearhardt, Lumeng. 10. van Jaarsveld CH, Llewellyn CH, Johnson L, 25. Davis CM. Results of the self-selection of diets
Statistical analysis: McCaffery, Appugliese, Kaciroti, Wardle J. Prospective associations between by young children. CMAJ. 1939;41(3):257-261.
Lumeng. appetitive traits and weight gain in infancy. Am J 26. Fomon SJ, Filmer LJ Jr, Thomas LN, Anderson
Obtained funding: Miller, Lumeng. Clin Nutr. 2011;94(6):1562-1567. doi:10.3945/ajcn. TA, Nelson SE. Influence of formula concentration
Administrative, technical, or material support: 111.015818 on caloric intake and growth of normal infants. Acta
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grant R01HD084163 from the Eunice Kennedy 2013;21(3):562-571. doi:10.1002/oby.20091
28. Timby N, Domellöf E, Hernell O, Lönnerdal B,
Shriver National Institute of Child Health and 12. Worobey J, Lopez MI, Hoffman DJ. Maternal Domellöf M. Neurodevelopment, nutrition, and
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role in the design and conduct of the study; 1016/j.jneb.2008.06.005 with bovine milk fat globule membranes:
collection, management, analysis, and 13. Stifter CA, Anzman-Frasca S, Birch LL, Voegtline a randomized controlled trial. Am J Clin Nutr. 2014;
interpretation of the data; preparation, review, or K. Parent use of food to soothe infant/toddler 99(4):860-868. doi:10.3945/ajcn.113.064295
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the manuscript for publication. study. Appetite. 2011;57(3):693-699. doi:10.1016/j. HP. Short-term effect of oil supplementation of
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