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JOURNAL OF PEDIATRICS • www.jpeds.com

ORIGINAL

Greater Breastfeeding in Early Infancy Is Associated with Slower WeightGain among High Birth Weight Infants Amy R. Goetz, PhD, Constance A. Mara, PhD, and Lori J. Stark, PhD

Objective To examine whether feed!29 patterns from birth to age 6 months modify the association between birth weight and weight at 7-12 months of age.Study design Longitudinal mixed models were used to examine feeding trajectories across categories of birthweight and weight at 7-12 months of age in 1799 mother-infant dyads enrolled in the Infant Feeding Practices Study ll. The percentage of breast milk received and the average daily formula consumption were calculated from birthto 6 months of age. Birth weights were classified as high (24000 g) and normal (22500 g and <4000 g). Weights at7-12 months of age were categorized as high (z score >I) or normal (z score A secondary analysis was per-fomed using categories defined by birth weight adjusted for gestational age percentiles (>90% and 10th-90th percentile).Results High birth weight (HBW) infants with high weights at 7-12 months of age demonstrated a rapid declinein the percentage of breast milk feedings compared with HBW infants with normal weights at 7-12 months of age.Normal birth weight infants with high weights at 7-12 months of age received a lower percentage of breast

milk and had greater absolute intakes of formula than those with normal weights at 7-12 months of age; these

asso- ciations did not vary over time. Results were similar when infants were categorized by birth weight

percentiles. Conclusions A lower proportion of breast milk feedings was associated with excess weight at 7-12

months of age in HBW infants. These findings suggest an initial target for obesity prevention programs focusing

on the first 6 months after birth. (J Pediatr

any factors that are present in the first 1000 days of life (ie, from conception to age 2 years) possess a strong rela-

tionship with later weight,l but a high birth weight (HBW, 24000 g) is a consistent predictor of later overweight or

obesity in childhood, adolescence, and adulthood.2•10 In a large prospective cohort study, the prevalence of obesity

was nearly double among HBW infants from early childhood to adolescence compared with normal birth weight (NBW, 2500-

3999 g) infants.il Moreover, 36% of youth who were obese at 14 years of age had a birth weight 24000 g." In addition to obesity,

'4-16 HBW infants also have increased risk for comorbid medical problems including type 2 diabetes12'13 and cardiovascular

concerns.

Given these concerns, a better understanding of the mechanisms that shape the association between HBW and later obesity

is needed.9 Prenatal (eg, prepregnancy overweight/obesity and diabetes mellitus) and postnatal influences (eg, breast milk feeding,

19 introduction to cereal, feeding practices, and eating appear to be important in determining later weight trajectories.

An understanding of potentially modifiable practices may provide insight as to how HBW infants become obese children and

inform targeted prevention efforts to improve growth patterns and reduce the risk for overweight/obesity.

Exclusive breastfeeding is protective against high weight20 and is recommended by the American -

Academy of Pediatrics for

the first 6 months. 21 Because breastfeeding rates can be improved with education and support, 2225 we examined associations

between feeding practices from birth to 6 months of age and weight-for-age in months 7-12 of infancy using observational

data from the Infant Feeding Practices Study Il. We hypothesized that HBW infants would receive a lower percentage of breast

milk and consume more formula than NBW infants. We further hypothesized that HBW infants with high weight z scores at

7-12 months of age would consume a lower percentage of breast milk and higher volume of formula compared with HBW

infants with a normal weight z score at 7-12 months of age.

Methods

The Infant Feeding Practices Study Il (JFPS Il) was a longitudinal survey of 4902 women in the US conducted by the Food

and Drug Administration and Centers for Disease Control and Prevention from

HBW High birth weight NBW Normal birth weight IFPS Il Infant Feeding Practices Study Il

BMI Body mass index

LGA Large for gestational age

AGA Appropriate for gestational age

GDM Gestational diabetes mellitus

% -lDTDqS

From tho Division of Behavioral Modicine and Clinical Psychology. Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Supported the National Instituto ot Diabetes Digestive and Kidney Disoasos 032 DK063929). The authors doclaro no conflicts ot interest.

0022-34M - front maur. 0201 a Elsevier Ire. dØts

https;'.'cEorgto.1016..1 ipøda20te.06.@4

THE JOURNAL OF PEDIATRICS • www.jpeds.com

May 2005 to June 2007. euds were eligible if

the mother was 218 years of age and the infant was a single-

ton born at >35 weeks of gestation with a birth weight 22.25

kg. Infants were ineligible if they had an illness or condition

that would impair feeding in the first year. Following the

completion of an initial prenatal questionnaire, mothers com-

pleted postnatal questionnaires monthly (neonatal, months 2,

3, 4, 5, 6, 7) and then every 7 weeks (months 9, 10.5, 12) until

the infant was 12 months of age. Additional information about

the IFPS Il is presented elsewhere. 26 Given that this was a sec-

ondary analysis of deidentified data, the current study was not

considered human subjects research by the Cincinnati Chil-

dren's Hospital Medical Center Institutional Review Board and

did not require Institutional Review Board approval.

Maternal information collected prenatally included age, race

and ethnicity, parity, smoking, prepregnancy body mass index (BMI), and poverty-to-income ratio. Gestational weight gain was assessed via self-report at the first postnatal survey. De- livery and neonatal information included gestational age (in

weeks), method of delivery, infant sex, and birth weight (in grams). Following the definition used in 2 recent meta- analyses, absolute birth weight was categorized as high (24000 g) or normal (22500 and <4000 Based on sex-specific fetal growth reference tables,27 birth weight percentiles were classified as large for gestational age (LGA, birth weight > 90th percentile) or appropriate for gestational age (AGA, 10th- 90th percentile).

At each postnatal questionnaire from birth to 6 months, mothers completed a food frequency measure reporting the average number of infant feedings of breast milk, formula, and other milk (eg, soy, rice milk) per day during the previous 7 days. The percentage breast milk variable was calculated at each

postnatal survey as follows 2B: [(number of breast milk feedings/

(number of breast milk + formula + cow's milk + other milk feedings)) x 100%. The percentage of breast milk was calcu- lated for each completed postnatal survey through 6 months;

mother-infant dyads could have up to 6 measurements.

Mothers who offered formula to their infants during the first

6 months were asked to indicate the approximate number of

ounces consumed per feeding from birth to 6 months. Re-

sponse options included 1-2, 3-4, 5-6, 7-8, and 8 or more

ounces. Response options were converted to the midpoint (ie,

1.5, 3.5, 5.5, 7.5, and 8.5).29 The midpoint formula consump-

tion and the average number of formula feedings per day were

used to estimate the average daily formula consumption in

ounces per month from birth to 6 months. Because not all

mothers offered formula in the first 6 months, only those re-

porting formula feedings during at least I measured time point

were included in analyses using this variable. Once an infant

had been given formula on a postnatal survey, the infant re-

mained in the formula group for all subsequent time points

even if reverting back to exclusive breastmilk.

Infant weight and length were obtained by maternal report

on postnatal questionnaires at the month 3, 5, 7, and 12 surveys.

The appointment date and measurements were obtained from

the infanes most recent doctor's appointment. Because of con-

cerns about parent-reported infant length'* we used weight

28

Volume 201 • Octob

z scores rather than weight-for-length or length

measur

ments. Infants with at least 2 weight measurements

were in-

cluded, and at least 1 measurement must have been

obtained

at the month 7 (n = 414) or 12 (n = 1385)

survey. Weight-for-

age z scores were calculated using the sex-specific

Centers for

Disease Control and Prevention national

growth reference

data.30 Biologically implausible z scores were

excluded. Weight

was dichotomized as az score (high) or

(normal) at 7-12

months of age.

Descriptive statistics are reported as means (with SDS) or

medians (with IQRs) and frequencies unless otherwise indi-

cated. Longitudinal mixed effects models were fit using

re-

stricted maximum likelihood with an unstructured covariance

pattern to allow for an unbalanced data structure (ie, unequal

number of measurements and measurement intervals) and cor-

relations between infants. Several models were estimated to de-

termine the most robust statistical model for the associations

between group and feeding practices from birth to 6 months.

Full group analyses examined feeding practices across catego-

ries of absolute birth weight (high vs normal) and birth weight

percentile (LGA vs AGA).

Three models were estimated. Model 1 was an unadjusted

linear model examining the relationship between group

with

and

feeding trajectories. Model 2 was composed of model I

adjustment for covariates that could potentially alter the as-

sociation between early feeding or birth weight: mother's age,

prepregnancy BMI, race/ethnicity (white used as reference),

poverty-to-income ratio, gestational age (not used for LGA or

AGA comparisons), and infant sex (male as reference). Model

3 was composed of model 2 with a quadratic component to

determine if trajectories were nonlinear. The respective terms

age and age2 were used to capture the linear and non-linear

effects of time (chronological infant age) on the outcome vari-

able, and whether the outcome varied as a function of group

(ie, group x infant age interaction). Random intercepts and

random slopes were included to allow for infant-specific varia-

tion in the intercepts and rates of change. For all models,

goodness-of-fit was estimated using deviance (-2 x log- likelihood), Akaike's information criteria, and Bayesian infor-

mation criteria for which lower values represent better model

fit. All analyses were conducted in Stata 15 (StataCorp LP,

College Station, Texas) and using the function "mixed," the pro-

cedure for estimating multilevel mixed-effects regression models.

Results

Birth weight was available for 3389 infants. Of these, 1521 mother-infant pairs were excluded for missing weight infor- mation at 7-12 months of age, and 68 were excluded for missing covariate information. The final sample size was 1799 (HBW, n = 209) for the analysis of percentage breast milk and 1265 (HBW, n = 133) for the average daily formula consumption. Because not all infants received formula and the timing of in- troduction varied, the sample size and mean number of ob- servations is lower for formula consumption than analyses examining percentage breast milk. Information at all 6 post-

Goetz, Mara, and Stark

Table I. Baseline demographics and dyadic characteris- tics as a function of infant absolute birth weight

Characteristics NBW (n-1590)

Mother

Prepreqnancy BMI, kg/m2 26.44 ± 6.51 Gestational weight gain, kg 13.70 ± 6.09

HBW(n-209)

28.83 ± 7.46 15.69

Age, Y Primlparous, % Prenatal smoklng, %

PIR, % Caucasian, % Cesarean delivery, % Gestational diabetes, %

Infant

29.70 ± 5.36

29.8

7.4

36.7

86.6

27.8

6.5

± 6.94 30.11 ± 4.91

20.9

2.4

35.4

91.4

37.3

7.8

value

<001

<001

.29

.93

<001

.77

Birth weight, g Infant sex, % male Gestational age, wk

HR, povertrto•lncome rado.

3379.15 ± 357.10 4267.91 ± 22273 <001 47.8 62.2 <001

39.26±1.23 39.99±1.02 <001

natal surveys was available for 1267 (70.4%) respondents for the percentage breast milk outcome and 521 (41.2%) for average daily formula consumption. Mean observations across all full group and subgroup analyses ranged from 5.5-5.6 for per- centage breast milk and 4.5-4.6 on average daily formula consumption.

Mothers of HBW infants were more likely to have a greater prepregnancy BMI and gestational weight gain and were more

likely to be white, multiparous, and less likely to smoke rela-

tive to mothers of NBW infants (Table I). HBW infants were

more likely to be male, born by cesarean delivery, and had a longer gestation. Thirty-three percent of HBW infants (n = 69)

and 17% of NBW infants (n = 277) had high weight z scores

(>1) at 7-12 months of age. Of the 209 HBW infants, 85% (n = 177) were also LGA using

birth weight percentiles and the remaining 15% (n = 32) were

AGA. Sixty-four infants who were previously coded as NBW

were classified as small-for-gestational age (<10th percentile)"

and subsequently removed from the IGA vs AGA analyses. Of

the 1526 remaining NBW infants, 4% (n = 61) were classi-

fied as LGA and the remainder were AGA (n = 1465). For these

groups, the final sample sizes for percentage breast milk and

daily formula consumption were 1735 (LGA, n = 238) and 1217

(LGA, n = 156), respectively. Thirty-six percent of LGA infants

(n = 87) and 17% of AGA infants (n = 254) had high weight

z scores at 7-12 months of age.

For the whole sample, breast milk comprised 67.08%

(SD = 42.68) of total milk feeds at the first postnatal ques-

tionnaire and 47.31% (SD = 47.03) in month 6. In the first post-

natal survey, 24% of mothers fed 0% breast mdk, rising to 47%

at 6 months. Feeding 100% breast milk was reported by 48%

of mothers in the first postnatal questionnaire and 34% of

mothers at 6 months. Among the subset of mothers who fed

formula, the mean volumes were 18.81 (SD = 14.56) and 26.22

(SD = 14.44) ounces per day initially and at month 6. The

median number of formula feedings per day in the first post-

natal survey was 6 (IQR, 2-8) and 5 (IQR, 3-6) at month 6.

A drop in the percentage of breast milk feedings occurred

in all participants in the first few months; this decline leveled

off over time (Table Il and Figure 1; available at

www.jpeds.com).Daily formula consumption increased in early

infancy and leveled off in later months. No significant effects

of group or group x infant age were found for percentage of

breast milk feedings or formula consumption. Results were

similar when analyzed using LGA and AGA birth weight per-

centilcs (Table Ill and Figure 2; available at www.jpeds.com).

The percentage of breast milk feedings gradually declined

across the first 6 months of infancy for HBW infants (Table IV).

HBW infants with high weights at 7-12 months of age dem-

onstrated an early nonlinear decline in the percentage of breast

milk feedings (a significant interaction of HBW-high weight

group and infant age2) from birth to 6 months compared with

HBW infants with normal weights at 7-12 months of age (Figure 3). Although formula intake increased over time, there

was no significant group or group x infant age interaction. In

Table IV. Unadjusted and adjusted* longitudinal mixed models for the association between categories ofHBW group/ weight-for-age status and percentage breast milk (n = 209) and daily formula consumption (n = 133) between birth to 6 months

HBW-hiqh

Age HBW-hlgh x age

HBW-high x age2

Model fit statisUcs

Model 1

B (95% CO

Percentage breast milk

-10.57 (-22.84. 1.70)

-0.52 (-014.-0.30)' -0.43 (-0.81, -.05)

10 036 10 052 10092

Dally formula consumption

4.22 (-1.28, 9.72)

0.48 (0.29, 0.68)t

-.09 (-0.39, 0.22)

4650 4666

4701

HBW-hiØ. intMB With weight4M-age.

Model

O (95% Cl)

Percentage breast milk

-8.29 (-20.72, 4.14) -0.52 (-0.74, -0.30)t

-0.43 (-0.82, -.05)

10 018 10 051 10 133

Model 6 (95% C')

Percentage breast milk

-7.26 (-19.72, 520) -0.75 (-1.10, -0.39)t

-0.94 (-1.55, -0.34)t

.01 (-.oo, .02?

.03 (.00, .05)

10 002 10 038 10 130

•Models ve adpsted motwr•s prepregnancy BMI, qe<atimal age, infant sex, ræe/ethnlcity, and PIR..001. .05.

Greater Breastfeeding in Early Infancy Is Associated with Slower Weight Gain among High Birth Weight Infants

6:15 PM

11/2/2019

THE JOURNAL OF PEDIATRICS • www.jpeds.com

80 HBW-normal normal or high weights at 7-12 months of age

70 Figure 6; available at www.jpeds.com).

60

30 HBW-high

20

10

2 3 4 5 6 Time (months)

30 HBW-high

25

20

HBW-norma1

10

5

Discussion

A robust association exists among infants born at a HBW

later risk for overweight/obesity 2A7•iMS

• however, not all HBW

infants follow this trajectory. To better understand the asso-

ciation between modifiable factors and risk for excess weight

among HBW infants, we examined breast and formula feeding

from birth to age 6 months. It was hypothesized that, irre-

spective of weight status at 7-12 months of age, infants born

heavy (HBW and LGA) would receive a lower ratio of breast

to nonbreast milk and consume more formula compared with

infants born at a normal weight (NBW and AGA). However,

these differences were not found, regardless of how infant birth

weight was defined (using absolute birth weight or birth weight

percentiles). These results are consistent with one other ret-

rospective study that found no differences between NBW and

HBW infants on infant eating behaviors or maternal feeding

practices.

We also hypothesized that infants born heavy (HBW or LGA)

with a high weight at 7-12 months of age would consume a

lower percentage of breast milk and higher volume of formula

compared with infants born heavy and with a normal weight

2 3 4 5 6

Time (months)

Figure 3. Unadjusted percentage breast milk and average daily formula consumption stratified by categories of HBW and weight z score at 7-12 months of age.

the LGA infants, the percentage of breast milk feedings de- creased and formula intake increased over time (Table V; avail-

able at www.jpeds.com). LGA infants with high weights at 7-12

months of age demonstrated a greater decrease in the per-

centage of breast milk compared with IGA infants with normal

weights at 7-12 months of age though the nonlinear interac-

tion failed to reach significance (Figure 4; available at

www.jpeds.com).

The percentage of breast milk feeding rapidly decreased in

the early months for all NBW infants (Table VI; available at

www.jpeds.com).Amain effect of group indicated that NBW

infants with high weights at 7-12 months of age received a lower

percentage of breast milk compared with those with normal

weights at 7-12 months of age and this relationship did not

vary over time. Across all NBW infants, formula consump-

tion rapidly increased in the early months and then leveled off.

Compared with NBW infants with normal weights at 7-12

months of age, those with high weights at 7-12 months of age

received more ounces of formula per day and this relation-

ship did not vary over time (Figure 5; available at

www.jpeds.com).Findings were similar for AGA infants with

at 7-12 months of age. The results showed that among HBW

infants with high weight at 7-12 months of age (based on a

previously used breast milk feeding rapidly de- dined in the earliest months, compared with HBW infants with

a normal weight at 7-12 months of age. In other words, among infants who were heavy at birth, other milks/formula were in- troduced earlier in infants with high weights at 7-12 months of age than in those with normal weights at 7-12 months of age. Findings were similar regardless of whether infants born heavy was defined as HBW or LGA.

Infants born at a normal weight who proceeded on a high weight trajectory at 7-12 months of age consumed a lower per- centage of breast milk and had greater formula intake com- pared with those with normal weight at 7-12 months of age. Our results are consistent with findings that have shown that HBW infants who achieved a normal weight-for-length at 7-8 months of age appeared to respond better to internal cues of satiety compared with HBW infants with a high weight-for-length. 19 Moreover, others have shown that heavy

offspring born to mothers with overweight/obesity and dia-

betes have rapidly rising BMIs in the first several years of life.i7

Taken together, both pre- and postnatal factors may elevate risk

for continued weight gain among infants born heavy.

In the current study, infants who were born heavy and

showed a gradual reduction in breast milk feedings also showed

slower weight gain than those with a more rapid reduction in

breast milk. These results suggest that a greater proportion of

breast milk feedings may buffer against high weight at 7-12

months of age. Prolongation ofbreastfeeding has received much

attention20•31v32as a method to reduce the risk of overweight. 20

In a retrospective cohort study, breastfeeding 212 months was

associated with a similar BMI at 4 years among AGA and LGA

Goetz, Mara, and Stark 30

er 2018

suggesting that a longer duration ofbreastfceding may

protect against excessive weight gain for infants born heavy. higher protein content than breast milk and the use of formula months, compared with the intakes and growth patterns of

Although the current study examined potentially modifi- able feeding practices, it is important to reflect on other pre-dictors of breastfeeding difficulty such as maternal weight,delivery mode, and maternal gestational diabetes mellitus(GDM) that could be confounding the association betweenbreastfeeding and later weight status in infants born heavy. Ma-ternal overweight/obesity has been previously associated withreduced intention to breastfeed, shortened duration ofbreastfeeding, and delayed onset of lactogenesis 11,35 al-though the mechanisms that drive these relationships (eg, ana-tomic, psychosocial) are not well understood.% Although ourstudy showed a larger proportion of prepregnancy overweight/obesity among mothers of infants with HBW and high weightat 7-12 months of age (72.5%) compared with those with normal weights at 7-12 months of age (63.6%), this differ- ence was not statistically significant. Delivery mode may also contribute to poor breastfeeding -87-39 as emergency cesarean de- livery is associated with shortened breastfeeding duration com- pared with spontaneous vaginal delivery.40 However, our study showed no differences between HBW subgroups on method of delivery.

c Maternal GDM is a risk factor increasing the likelihood of

delivering a heavy infant and reduced duration of breastfeeding. at has been shown to differ between

LGA infants born to mothers with and without GDM,41 and breastfeeding at least 3 months appears protective against over-

weight in children born to mothers with GDM,42 the current

study did not find differences in maternal GDM between the

HBW subgroups. Overall our study did not find relation- ships between breast milk feedings and other prenatal and in-

trauterine indicators that are traditionally associated with

reduced breastfeeding.

Encouragingly, breastfeeding practices can be increased fol-

lowing brief education. 2Y25'0 For example, telephone-based

support increased the duration of any and exclusive breastfeeding among obese women. 22 The current findings

convey the importance of addressing early feeding and pro-

viding support to mothers of infants born heavy to curtail a

high weight trajectory and potentially impact later obesity. Fur-

thermore, the critical period of infancy which encompasses

multiple well-child visits in the first year of life may be an ap-

propriate front line for tailoring anticipatory guidance and edu-

cation strategies around sustained breastfeeding specifically for

mothers of infants born heavy.

Although HBW infants have almost double the prevalence

of overweight/obesity at later ages compared with NBW infants,

it is still the minority of either population that become obese."

It may be that this relatively low incidence resulted in failure

to find group differences between our HBW and NBW groups.

Breastfeeding was not different between these groups but did

ORIGINAL ARTICLES

distinguish between HBW infants with normal or high weightsat 7-12 months of age. These findings suggest that following

nisms that may be associated with excess weight gain would

to mitigate obesity risk among infants at high risk for obesity (ie, birth weight 24000

these data come from an observational study, lack of causal- ity and possible confounding are important methodologic concerns. Although the current study controlled for prenatal and sociodemographic characteristics, there are likely other

factors that could not be adjusted for that may impact these

results. In addition, data were collected via maternal report

which may contain inaccuracies, specifically with report of

absolute birth weight, gestational age, and weight at 7-12 months of age. Generalization of these findings is also a

concern. Compared with women who participated in other

nationally representative surveys,26 mothers in the IFPS Il

were more likely to be older, employed, and more highly educated. They were more likely to breastfeed for longer

durations, to have fewer children, and were less likely to be

low income or smoke. Finally, these data are more than 10

years old and although breastfeeding has been largely stable

over recent years (eg, 2005-2008 vs 2009-2012), u additional

contemporary analysis and HBW specific cohort studies are

needed to enhance understanding of the HBW-obesitypathway.

A strength of the study was the longitudinal mixed modeling

approach that allowed for an examination of feeding prac-

tices over birth to age 6 months.

In conclusion, although there is a strong association between

HBW and later overweight/obesity, not all HBW infants will

follow this trajectory. The current study examined relation-

ships between feeding practices among categories of birth weight and weight at 7-12 months of age. HBW infants with

later high weight-for-age showed an early decline in breast milk

intake over the first 6 months of life compared with HBW

infants with normal weights at 7-12 months of age. These as-

sociations held regardless of whether HBW was defined by ab-

solute birth weight or birth weight percentiles. Given the complexity of accurately calculating gestational age,46A8 abso-

lute birth weight appears to be an equally appropriate as well

as established risk marker) for future excess weight. Future

studies should seek to elucidate other variables (eg, comple-

mentary feeding, sleep) that may be implicated in the HBW-

obesity association.

Submitted for publication Jan 23.2018; last revision received May 31.2018; accepted Jun I. 2018

Reprint requests: Amy R. Goetz. PhD. Division of Behavioral Medicine and

Clinical Psychology. Cincinnati Children's Hospital Medical Center, 3333

Burnet Avo MLD 7039, Cincinnati, OH 45229. E-mail: [email protected]

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Greater Breastfeeding in Early Infancy Is Associated with Slower Weight Gain among High Birth Weight Infants 31