Eur J Epidemiol (2009) 24:449467

DOI 10.1007/s10654-009-9356-5

DEVELOPMENTAL EPIDEMIOLOGY

Period-specific growth, overweight and modification

by breastfeeding in the GINI and LISA birth cohorts
up to age 6 years
Peter Rzehak Stefanie Sausenthaler Sibylle Koletzko Carl Peter Bauer
Beate Schaaf Andrea von Berg Dietrich Berdel Michael Borte
Olf Herbarth Ursula Kramer Nora Fenske H. -Erich Wichmann
Joachim Heinrich
Received: 22 September 2008 / Accepted: 25 May 2009 / Published online: 12 June 2009

Springer Science+Business Media B.V. 2009

Abstract Childrens weight/growth development is agespecific and may be influenced by breastfeeding. We

therefore assessed velocities of weight, length, body-massindex and overweight/obesity development from birth up to
age 6 years overall and in relation to breastfeeding. The
method of this study is based on pooled data of the birthcohorts GINI-plus and LISA-plus and follows 7,643 healthy full-term neonates in four study-centers in Germany.
Up to nine anthropometric measurements are available.

This study is conducted by the authors for the GINI LISA Study
Group. The members of the GINI LISA Study Group are given in
Appendix.
P. Rzehak (&)
S. Sausenthaler
H. -ErichWichmann

J. Heinrich
Institute of Epidemiology, Helmholtz Zentrum Munchen,
German Research Center for Environmental Health, Ingolstadter
Landstrasse 1, 85764 Neuherberg, Germany
e-mail: peter.rzehak@helmholtz-muenchen.de

Overweight/obesity is percentile-defined according to

WHO-Child-Growth-Standards. Fully-breastfed is defined
as breastfed for at least 4 months. Piecewise-linear-random-coefficient-models were applied to assess growth
trajectories and velocities between 03, 36, 612, 1224
and beyond 24th months. Velocities for weight-, lengthand BMI-development are highest in the first 3 months
after birth and diminish, with differing pace, in the periods
that follow. For overweight and obesity, peak-velocities are
estimated in periods 612 and 36 months. The difference
in the velocity of weight gain for breastfed vs. other children is -18 g/month in the first 3 month, -93 g/month

M. Borte
Municipal Hospital St. Georg, Teaching Hospital of the
University of Leipzig, Childrens Hospital, Leipzig, Germany
M. Borte
Department of Pediatrics, University of Leipzig, Leipzig,
Germany

P. Rzehak
H. -ErichWichmann
Institute of Medical Data Management, Biometrics and
Epidemiology, Ludwig-Maximilians University of Munich,
Munich, Germany

O. Herbarth
Department of Human Exposure Research and Epidemiology,
UFZ Leipzig-Halle, Leipzig, Germany

S. Koletzko
Dr. von Hauner Childrens Hospital, Ludwig-Maximilians,
University of Munich, Munich, Germany

O. Herbarth
Faculty of Medicine, Department of Environmental Medicine
and Hygiene, University of Leipzig, Leipzig, Germany

C. P. Bauer
Department of Pediatrics, Technical University of Munich,
Munich, Germany

U. Kramer
Institut fur Umweltmedizinische Forschung, IUF, University of
Dusseldorf, Dusseldorf, Germany

B. Schaaf
Medical Practice for Pediatrics, Bad Honnef, Germany

N. Fenske
Department of Statistics, Ludwig-Maximilians University
Munich, Munich, Germany

A. von Berg
D. Berdel

Department of Pediatrics, Marien-Hospital Wesel, Wesel,
Germany

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P. Rzehak et al.

between month 3 and 6, -14 g/month between month 6

and 12 and -3 g/month beyond the 24th month. Velocities
in length are not different between breastfed and nonbreastfed children. Over time, a slightly lower risk (difference \ 2%) of being overweight was estimated for
breastfed children, after adjustment for study-center, socioeconomic-status and maternal smoking in pregnancy.
Infants fully-breastfed gain less weight, but grow equally in
length in the first 12 months of life versus mixed or formula-fed children. The protective effect of breastfeeding
on becoming overweight is related to its weight-velocitymodifying-effect in early infancy.

nates living in Germany. This study evaluates whether

velocities of growth in weight and length, body-mass-index
(BMI), overweight and obesity development vary in different life periods of early and later infancy and further
childhood. Moreover, individual variations and the potential modifying effect of breastfeeding on these velocities of
growth are investigated.

Keywords Body mass index
Breastfeeding

GINI and LISA birth cohort studies
Length
Height

Weight
Overweight
Obesity
Period specific
growth rates
Kompetenznetz adipositas

Data from two ongoing German birth cohorts of healthy

full-term neonates born between 1995 and 1999 in Munich,
Wesel, Bad Honnef and Leipzig were combined for longitudinal analyses of growth.
The GINI-plus (German Infant Nutritional Intervention)
study is an ongoing birth cohort, initiated to prospectively
investigate the influence of nutrition intervention during
infancy plus air pollution and genetics on allergy development. Between September 1995 and July 1998 a total of
5,991 healthy full-term newborns were recruited in
obstetric clinics in Munich and Wesel. The cohort is
composed of an intervention (n = 2,252) and a non-intervention group (n = 3,739). Group assignment has been
based on family history of allergy. The intervention comprised nutritional advice promoting breastfeeding for at
least 4 months and a randomized trial on the effect of
hydrolyzed formula vs. conventional cow-milk formula in
preventing allergies. Details on study design are described
elsewhere [12, 13].
The LISA-plus-study is an ongoing population-based
birth cohort study of unselected infants, designed to assess
Influences of Lifestyle related Factors on the Immune
System and the Development of Allergies in Childhood.
Between November 1997 and January 1999, n = 3,097
healthy full-term newborns were recruited from 14
obstetrical clinics in Munich, Leipzig, Wesel, and Bad
Honnef. Details on study design are published elsewhere
[14, 15]. At 6 years follow-up both birth cohort studies
share identical standard operating procedures and before
the 6 years follow-up there were very similar study protocols. Scheduled timing of follow-ups for questionnaires
were at 0, 6, 12, 24, 36, 48, 60 and 72 months in the GINIplus study and at 0, 6, 12, 18, 24, 48, and 72 months in the
LISA-plus study.
For both studies approval by the respective local Ethics
Committees (Bavarian General Medical Council, University of Leipzig, Medical Council of North-Rhine-Westphalia) and written consent from participants families
were obtained.

Abbreviations
BMI
Body mass index
GINI study German Infant Nutritional Intervention
study
LISA study Influences of Lifestyle related Factors on the
Immune System and the Development of
Allergies in Childhood study
SES
Socio economic status

Introduction
Due to the epidemic prevalence of overweight and obesity
in many parts of the world, numerous studies on overweight development in children have been published [1].
However, longitudinal data from birth cohorts analyzing
the course of weight, length and overweight development
from birth up to school-age, with more than a few measurements over time, are still scarce [1, 2]. Moreover, most
studies report only population averaged estimates, but do
not report the individual variation in growth trajectories
and thus do not allow assessment of subject-specific heterogeneity in baseline values and variation in velocity of
growth development. Even more important, only few
papers report different rates of change (velocities of
growth) at several periods in infancy and further childhood
in due detail and with more than one measurement in early
infancy [26]. A protective effect of breastfeeding
regarding later overweight has been shown by several
studies [710]; but, this effect is not consistent [11].
Thus, the aim of this study is to assess growth in length
and weight from birth up to the age of 6 years in large
population-based birth cohorts of healthy full-term neo-

123

Methods
Study design and population

Period-specific growth rates and breastfeeding

Measurements
Weight, length, BMI, overweight and obesity
Anthropometric measurements of weight and length were
obtained by the records of the preventive medical checkups in the well-baby check-up books (U-Untersuchungen). These are repeated physical examinations of the
child conducted by a pediatrician at birth, at day 310,
week 46, month 34, 67, 1012, 2124, 4348, and at
the 6064th month of life (designated time schedule) to
monitor physical growth and indications of adverse health
outcomes. Due to variation in age at each measurement of
weight and length, data are available for almost every
month in the first 2 years of life and in due detail for further
childhood up to the age of 6 years. BMI is defined as
weight in kilogram divided by squared length in meter.
Overweight and obesity is defined as the 90th and 97th
percentile of the standard deviation score of BMI, respectively, (i.e. C1.28 and 1.88) as derived from the sex and
age-specific WHO-Child-Growth-Standards for 05 year
(B1,856 days) old children and according to the International WHO Growth Standards for School-Aged Children
and Adolescents for children older than 1,856 days [16,
17]. Software-macros and documentation of these WHOreference-standards can be downloaded from the following
URLs: http://www.who.int/childgrowth/software/en/ and
http://www.who.int/growthref/tools/en/.
Breastfeeding
Breastfeeding was defined as fully breastfeeding for at least
4 months versus other postnatal feeding practices including
formula- or mixed-feeding.

451

Briefly, such longitudinal models do not only account

for the correlated data structure due to repeated measurements, but in addition allow estimation of a separate
average slope for every specified time period by simultaneously fitting regression lines to every specified timesegment. These regression lines are connected at the end of
each period and thus allow the modeling of complicated
nonlinear growth trajectories by the sequence of simple
linear regression lines, which allows an interpretation of
period-specific change. By combining this model with a
multilevel approach, period specific growth curves can be
estimated for each individual and thus allow an assessment
for individual heterogeneity of growth in addition to the
average growth curve. This simplicity of linear approximation of complex non-linear growth curves and the possibility to assess individual heterogeneity in trajectories
influenced our choice of piecewise-linear random coefficient models over alternative ways of longitudinal data
modeling like Coles LMS-method or fractional polynomials [20, 21]. The use of piecewise linear-random-coefficient-models were also motivated by the attractive
property of the chosen model, that the theory of critical
time periods for growth can be reflected by specifying such
time periods explicitly [22]. The choice of time-segments
is based on previous literature discussing different time
windows for rapid weight gain [2326]. Within this statistical approach, a longitudinal form of regression and
logistic regression were applied for the outcomes of
weight, length, BMI and overweight/obesity, respectively.
A detailed description of the statistical models and methods, their interpretation and the software used is given in
the Appendix.

Results
Socio-economic status
Socio-economic status (SES) was operationalized as maximum completed years of schooling of either parent as
low (\10 years), medium (=10 years) and high SES
([10 years). We defined high SES as more than 10 years
of parental education, due to the different school-systems
between West- and East-Germany 20 years ago.
Statistical analysis
Piecewise-linear-random-coefficient models were applied
to assess subject-specific (individual) and populationaveraged (mean) growth trajectories and period-specific
velocities (rates of change per month) between 03, 36,
612, 1224 months and beyond the 24th month. Such
longitudinal models are described in detail in the books of
Singer et al. and Fitzmaurice et al. [18, 19].

Characteristics of the study population are listed in

Table 1. At birth, boys and girls differ in weight and length
but not substantially in average BMI, percentage of overweight or obesity, maternal smoking in pregnancy, gender
fraction within study center and SES. However, the percentage of breastfed infants is more than 2% higher in
female than male infants.
Development of weight, length, BMI, overweight
and obesity
Weight
Average birth weight for boys is estimated as 3,465 g and
as 3,262 g for girls (initial status at birth, Table 2, Model
A). Individual birth weights vary considerably as can be
seen graphically from Fig. 1, panel ab and numerically

123

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P. Rzehak et al.

Table 1 Characteristics of study population

Boys

Girls

n = 3,930

n = 3,713

Effect sizea
boys vs. girls

Total
n = 7,643

Mean or %

SD or
CI-95%

Mean or %

SD or
CI-95%

Hedges g
or OR

Mean
or %

SD or
CI-95%

Birth weight (g)

3,540.8

464.7

3,401.5

437.6

0.3

3,473.1

457.0

Birth length (cm)

52.3

2.5

51.5

2.4

0.3

51.9

2.5

BMI at birth

12.9

1.2

12.8

1.2

0.1

12.9

1.2

% Overweightb at birth

4.0 (157/3,930)

3.44.6

4.4 (165/3,713)

3.85.1

0.9

4.2 (322/7,643)

3.84.7

% Obesec at birth

0.9 (35/3,930)

0.61.2

1.3 (49/3,713)

1.01.7

0.7

1.1 (84/7,643)

0.91.3

% Infants breast-fed
C4 month

51.8 (1,963/3,790)

50.253.4

54.0 (1,921/3,560)

52.355.6

0.9

52.8 (3,884/7,350)

51.754.0

% Maternal smoking
in pregnancy

16.2 (635/3,920)

15.017.4

16.5 (612/3,702)

15.317.7

1.0

16.4 (1,247/7,622)

15.517.2

% Infants from study center

Munich

48.5 (1,905/3,930)

46.950.0

46.9 (1,740/3,713)

45.348.5

1.1

47.7 (3,645/7,643)

46.648.8

Leipzig

11.7 (460/3,930)

10.712.7

12.7 (473/3,713)

11.713.8

0.9

12.2 (933/7,643)

11.512.9

Bad Honnef

3.8 (148/3,930)

3.24.4

4.2 (157/3,713)

3.64.9

0.9

4.0 (305/7,643)

3.64.4

Wesel

36.1 (1,417/3,930)

34.637.6

36.2 (1,343/3,713)

34.637.7

1.0

36.1 (2,760/7,643)

35.037.2

[10th grade

61.4 (2,398/3,907)

59.862.9

61.6 (2,276/3,692)

60.163.2

1.0

61.5 (4,674/7,599)

60.462.6

=10th grade

29.6 (1,158/3,907)

28.231.1

29.9 (1,105/3,692)

28.531.4

1.0

29.8 (2,263/7,599)

28.830.8

\10th grade

9.0 (351/3,907)

8.19.9

8.4 (311/3,692)

7.59.3

1.1

8.7 (662/7,599)

8.19.3

% Parental education

For weight, length and BMI at birth Hedges g is calculated, which is the standardized mean difference between boys and girls. For all other
variables effects size is calculated as odds ratio (OR). An overview on these effect sizes and the respective formulas are given by Durlak et al.
[38]

Defined as C90th percentile of BMI at birth according to age and sex-specific WHO-child-growth standards [16]

Defined as C97th percentile of BMI at birth according to age and sex-specific WHO-child-growth standards [16]

from the 95%-reference range (initial status at birth,

Table 3).
In the first 3 months of life an infant adds on average
941.6 g/month, that is a girl or a boy weighs 2,825
(3 9 941.6) g more at the end of the 3rd month than at
birth. In the period 36 months the weight gain velocity
diminishes to 548.9 g/month and to 316, 235 and 188 g/
month in the time periods 612, 1224 months and beyond
the 24th month up to the age of 6 years, respectively. Thus,
the fastest increase in weight gain per month occurs within
the first 3 month of life. The difference in velocities
between the first and the second period is 393 g/month,
between the second and the third period 233 g/month and
81 and 47 g/month between the third and the fourth and the
fourth and fifth period, respectively.
These different weight gain velocities, in absolute terms
of weight development for the average birth weight boy
and girl over time, can be best seen from the darker and
thicker line depicted in Fig. 1, panel ab representing the
average growth trajectory. The thinner, fainter colored
lines are the individual trajectories for each child. Note that
Fig. 1, panel ab shows visually that weight gain velocities

123

in the different periods differ considerably from the average slopes, within each time period, and that the cumulative effect of these individual deviations result in a larger
spread of these individual weight trajectories during
infancy and childhood. The individual rates of weight gain
vary at maximum in the first 3 months of life (571
1,312 g) and range between 414 and 683 g/month for the
period 36 months (see 95%-reference ranges in Table 3).
The velocity in weight gain between months 6 and 12 does
not vary individually and is thus estimated in Table 2 as
316 g/month for all infants (therefore no range is listed
in Table 3). The respective 95% ranges for periods
1224 months and beyond the 24th month are 121350 g/
month and 99277 g/month, respectively.
From the correlations in the lower panel of Table 3, high
birth weight (initial status) is only small to moderately
correlated with the individual velocities of weight gain in
the periods 03 months (0.08), 36 months (-0.12) and
612 months (0.25). However, infants who experience a
steeper increase in the first 3 months of life have a much
lower velocity of weight gain between months 3 and 6 and
1224 (-0.93; -0.44), and vice versa. Beyond the 24th

548.9

316.0

235.4

188.0

6 to \12 months

12 to \24 months

24 to \72 months
186.6

241.6

309.5

504.9

933.7

189.4

228.1

323.5

598.3

951.5

186.5

241.6

309.4

505.4

933.5

3,585.8

3,378.4

189.5

228.1

323.5

598.4

951.7

3,515.4

3,308.0

Other

0.7

1.0

1.3

2.2

3.3

52.4

51.0

All

0.7

1.0

1.3

2.1

3.3

52.5

51.1

Breastfed

Model Bb

0.7

1.0

1.3

2.4

3.3

52.3

50.9

Other

0.7

1.0

1.3

2.1

3.3

53.1

51.8

Breastfed

Model Cc

0.7

1.0

1.3

2.4

3.3

52.9

51.6

Other

-0.02

-0.06

0.01

0.11

1.25

12.83

12.52

All

Model Aa

-0.02

-0.05

-0.01

0.08

1.25

12.86

12.53

Breastfed

Model Bb

BMI (kg/m2)

-0.02

-0.07

0.03

0.12

1.28

12.77

12.44

Other

-0.02

-0.05

-0.01

0.09

1.24

12.91

12.58

Breastfed

Model Cc

-0.02

-0.07

0.03

0.13

1.27

12.78

12.45

Other

Model C is based on the respective Model B adjusted for maternal smoking in pregnancy, study center and socio-economic status

Model B is based on the respective model A, however, supplemented by the main effect of breastfeeding and its interactions with the period specific change rate slopes

Model A is the respective longitudinal piecewise linear random effects regression model described in detail in the Appendix; allowing for an estimate of the baseline value and five
different change rates over time and for a main effect of sex. For outcomes weight, length and BMI it is based on a longitudinal version of multiple regression and for outcomes overweight and
obesity on its logistic regression equivalent. The table shows the population averaged or fixed effects estimates. Which change rates vary individually (random slopes) in addition to the initial
status (random intercept) is specified in Table 3

941.6

3 to \6 months

3,429.8

0 to \3 months

3,224.0

3,288.6

3,262.0

Breastfed

Breastfed

All

Other

Model Aa

Model Bb

Model Aa

Model Cc

Length (cm)

Weight (g)

Boys
3,465.1
3,494.4
Rate of change per month in period

Girls

Initial status at birth

Fixed effects

Table 2 Rates of change per month for the development of weight, length and body-mass-index from birth up to age 6 years

Period-specific growth rates and breastfeeding

453

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P. Rzehak et al.

with high length at birth show lower growth rates in the

first 3 months of life (-0.52), but higher growth rates in
period 36 months (0.53), and vice versa. Moreover, an
almost perfect negative correlation (-0.996) is estimated
between the growth rates in period 03 and 36 months.
BMI
BMI at birth is estimated as 12.8 and 12.5 kg/m2 for boys
and girls, respectively (Table 2, Model A). At each of the
first 3 months of life BMI increases on average by 1.25 kg/
m2. For the following two periods the velocity is reduced
substantially and in the periods beyond the 12th and the
24th month the rate is even slightly negative (Fig. 1, panel
ef). From the spread at birth and the parallel trajectories in
the graph it can be seen that infants relative weight varies
only in the initial value of BMI at birth (95% referencerange 11.114.5 and 10.814.2 kg/m2 for boys and girls,
respectively), but not in their individual slopes.
Overweight and obesity

Fig. 1 Subject-specific and population averaged development of

weight, length and BMI by sex from birth up to the age of 6 years

month, the rate of weight gain is positively correlated

with the rate in the first 3 months of life (0.25). Note
further, the correlations between the change rates in
periods 36, 1224 (0.22) and beyond the 24th month
(-0.32) and between the change rates of periods 1224
and beyond the 24th month (-0.46), indicating a individual complex form of tracking weight velocities during
infancy and childhood.
Length
Birth length is estimated as 52.4 and 51.0 cm for boys and
girls, respectively (Table 2, Model A). Birth length varies
considerably (Fig. 1, panel cd; 95%-reference-ranges in
Table 3).
Average growth rates are highest in the first 3 months of
life (3.3 cm/month) and decline substantially in the following periods. Individual velocities in length development
vary substantially in the first half year (Table 3). Infants

123

The percent of overweight and obese infants at birth are

estimated as 3.7 and 1.0% for boys and as 3 and 0.7% for
girls, respectively (Table 4, Models A). Note, these and the
following percentages (probabilities) are derived from the
logit coefficients given in Table 7 as described in the statistical section of the Appendix.
The velocity per month for overweight accelerates for
each period up to the 12th month, from 0.36% through
0.570.73% per month. Between months 12 and 24 the rate
slows down somewhat (0.35%). However, beyond month
24 the monthly rate becomes negative (-0.16%) resulting
in a reduction from the peak of 14.3% overweight girls at
month 24 to an estimated percentage of 6.6% at the age of
6 years. The respective percentages for boys are 17.5 and
8.1%.
The velocity for obesity is very small in the first
3 months (0.06% per month). However, during the period
of 36 months, a monthly increase of 0.25% is estimated,
followed by a positive rate of 0.18 and 0.14% in the periods
between month 6 and 12 and 1224, respectively. From the
24th month, the percentage of obese children declines by
-0.04% per month form the peak of 3.7% for girls and
5.2% for boys to 1.6 and 2.3%, respectively.
The development of overweight and obesity over time
are best seen by Fig. 2, panel ad depicting the estimated
percentage of being overweight or obese in different
periods after birth for boys and girls. Only population
averaged trajectories are shown as these measures are
dichotomies.

Boys

414; 683

121; 350
99; 277

3 to \6 months
6 to \12 months

12 to \24 months

24 to \72 months

0.22
-0.32

-0.46

Change rate past 3 by 12 months

Change rate past 3 by 24 months

Change rate past 6 by 12 months

Change rate past 6 by 24 months

Change rate past 12 by 24 months

-0.44

-0.32

0.22

0.24

-0.43

-0.94

0.24

-0.12

0.08

98; 275

128; 355

375; 635

567; 1,300

2,759; 4,230

2,553; 4,024

-0.44

-0.32

0.22

0.24

-0.43

-0.94

0.24

-0.12

0.08

101; 278

114; 342

468; 728

585; 1,318

2,695; 4,165

2,489; 3,959

95% of the subject-specific estimates are located in this range (see Appendix)

See respective footnotes Table 2

Change rate past 3 by 6 months

a,b,c

0.25

-0.93

Common rate by past 3 months

Common rate by past 24 months

Initial status by past 24 months

0.25

Initial status by past 12 months

-0.44

Common rate by past 12 months

-0.12

Initial status by past 3 months

Initial status by past 6 months

Common rate by past 6 months

0.08

Initial status by common rate

Correlations between change rates

571; 1,312

0 to \3 months

Rate of change per month in period

2,543; 3,981
2,746; 4,184

Girls

Initial status at birth

Other

-0.44

-0.32

0.22

0.24

-0.42

-0.94

0.24

-0.12

0.08

98; 275

128; 355

375; 636

564; 1,303

2,860; 4,312

2,652; 4,104

Breastfed

-0.44

-0.32

0.22

0.24

-0.42

-0.94

0.24

-0.12

0.08

81; 298

98; 358

454; 743

583; 1,321

2,789; 4,241

2,582; 4,034

Other

-1.00

0.53

-0.52

2.1; 2.3

2.0; 4.7

48.0; 56.6

46.7; 55.3

All

Breastfed

All
d

Model Aa

Model Bb

Model Aa

Model Cc

Length (cm)

Weight (g)

95% Reference ranges of initial status and change rates

Random effects

Table 3 Variation of subject-specific rates of change for the development of weight and length from birth up to age 6 years

-1.00

0.52

-0.51

1.9; 2.2

2.0; 4.7

48.2; 56.7

46.9; 55.4

Breastfed

Model Bb

-1.00

0.52

-0.51

2.2; 2.5

2.0; 4.7

48.0; 56.5

46.7; 55.2

Other

-1.00

0.55

-0.55

1.9; 2.2

1.8; 4.9

48.8; 57.3

47.5; 56.0

Breastfed

Model Cc

-1.00

0.55

-0.55

2.2; 2.5

1.8; 4.9

48.6; 57.1

47.3; 55.8

Other

Period-specific growth rates and breastfeeding

455

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P. Rzehak et al.

Table 4 Rates of change per month for the development of overweight and obesity from birth up to age 6 years
Fixed effects

Overweight (%)
Model A

All

Model B

Obesity (%)
b

Breastfed

Model C
Other

Breastfed

Other

Model Aa

Model Bb

All

Breastfed

Model Cc
Other

Breastfed

Other

Initial status at birth

Girls

2.99

Boys
3.74
Rate of change per month in period

3.07

2.71

3.58

2.90

0.70

0.68

0.67

1.02

0.86

3.85

3.40

4.56

3.70

1.01

0.99

0.97

1.53

1.29

0 to \3 months

0.36

0.34

0.47

0.39

0.50

0.06

0.05

0.09

0.08

0.13

3 to \6 months

0.57

0.42

0.67

0.53

0.76

0.25

0.19

0.31

0.28

0.40

6 to \12 months

0.73

0.49

1.00

0.66

1.20

0.18

0.09

0.29

0.14

0.39

12 to \24 months

0.35

0.41

0.26

0.61

0.42

0.14

0.17

0.11

0.24

0.13

24 to \72 months

-0.16

-0.16

-0.16

-0.14

-0.11

-0.04

-0.05

-0.04

-0.07

-0.05

Model A is based on the respective longitudinal piecewise linear random intercept logistic regression model described in detail in the
Appendix; allowing for an estimate of the baseline value and five different change rates over time and for a main effect of sex
b
Model B is based on the respective model A, however, supplemented by the main effect of breastfeeding and its interactions with the period
specific change rate slopes
c

Model C is based on the respective Model B adjusted for maternal smoking in pregnancy, study center and socio-economic status

Note the percentages listed in Table 4 are derived from the logit coefficients given in Table 7 as described in the statistics section of the
Appendix
Fig. 2 Population averaged
development of overweight and
obesity by sex from birth up to
the age 6 years

123

Period-specific growth rates and breastfeeding

457

Modification of velocities of weight, length, BMI,

overweight and obesity development by breastfeeding
Weight
Velocity of monthly weight gain for fully-breastfed infants
is lower for all periods except for the second year of life
when compared to mixed or formula-fed children (Table 2,
Model B). The largest difference in velocities between
these two groups is estimated for the period 36 months
(-93 g/month) and the smallest for the period beyond 24th
months (-2.8 g/month). Adjustments do not change these
results substantially (Table 2, Model C).
Length
Breastfeeding does not change velocities of growth in
length for analyzed periods, with the exception of month
36 (-0.3 cm/month), even after adjustment (Table 2,
Model B and C).
BMI
For each period, fully-breastfed children have a lower
velocity of monthly BMI change than mixed or formulafed children (Table 2, Model B). Although these differences in velocities are rather small it is interesting to note
that the rate of change in BMI becomes negative (i.e. BMI
reduces in absolute terms) in the second half year of life for
breastfed children, whereas for the other children the rate
of change in BMI becomes negative in the second year of
life (see Fig. 3, panel ab). Comparison of velocities
between Model B and C reveal that adjustments result in
only minor changes.
Overweight and obesity
Monthly change rates in the percentage of overweight and
obese children are positive for each period up to the 24th
month, and negative thereafter for both breastfed and
otherwise fed children (Table 4, Model B). Note, these
percentages (probabilities) are derived from the logit
coefficients given in Table 7 as described in the statistical
section of the Appendix. However, in the first three
periods up to the 12th month the velocities are lower for
breastfed children by -0.13% (0.340.47%), -0.25% and
-0.51% and -0.4%, -0.12% and -0.20% regarding
overweight and obesity, respectively. That means, the
difference in rates is doubling from period to period within
the first 12 month of life. Between months 12 and 24 fullybreastfed children have a higher velocity for becoming
overweight or obese versus otherwise fed children. However, as velocity is negative for the period after the 24th

Fig. 3 Population averaged development of body-mass-index, overweight and obesity by breastfeeding and sex adjusted for maternal
smoking in pregnancy, study center, parental education (SES) from
birth up to the age of 6 years. Note the respective darker line
represents the trajectory for breastfed, the fainter line that for the
mixed or formula-fed children

month, for both groups, a constantly lower percentage of

overweight and obese children is estimated for the breastfed group. Adjusted analyses do not result in substantial
differences (Table 4, Model C; Fig. 3 panel cf).

Discussion
Overall velocities for weight, length and BMI development
were highest in the first 3 months after birth and decreased
substantially thereafter. However, the monthly change rates
regarding overweight and obesity development are positive
up to the 24th month and are highest between periods 612
and 36 months for overweight and obesity, respectively.
Our results support some previous studies, which have
emphasized that very early infancy weight gain is a critical
period for later weight gain and overweight [2, 3, 24, 27]
and may somewhat question the often recommended period

123

458

of 24 months to define rapid weight gain [23, 26]. On the

other hand, the strong negative correlations of individual
rates of change in weight between the velocities at months
13 and 36 (listed in Table 3) indicate that high monthly
rates of weight gain in the first 3 month are somewhat
compensated by lower weight gain rates in the following
period.
It was shown that velocity of weight gain, overweight
and obesity were reduced in fully-breastfed infants, but not
length. Although differences were only 12% for overweight or obese children, these contrasts remain for the
whole study period even after adjustments for maternal
smoking in pregnancy, study center and SES.
Thus, the presented results support previous studies,
which have shown that there is a protective effect of
breastfeeding against later overweight [710] in contrast to
a study, which did not find a difference in fat mass at age of
5 years [11]. These results are also in line with the stated
protein-intake-hypothesis expecting excessive weight
gain in the first months of life due to a higher protein
intake, which may be due to the higher protein content of
formula-milk [28, 29]. Moreover, as the reducing effect of
breastfeeding is stronger regarding overweight and obesity
than for BMI, it gives further plausibility for a protective
effect, because it has been already shown that breastfeeding
does not shift the whole BMI-distribution but only the
upper tail [30].
On the other hand, the small overall contrasts of
breastfeeding for BMI, overweight and obesity development may raise a question regarding whether the definitions
of breastfeeding and overweight, and adjustments were
sufficient to avoid residual confounding. Moreover, to our
knowledge, no study has examined the reliability and
validity of the German medical checkups (U-Untersuchungen). However, recent publications on this issue
regarding anthropometric measurements within children in
other countries show that measurement deviations within
and between health personnel show acceptable reliability
[31, 32]. Furthermore, as all infants were recruited from
clinical settings, questions regarding sample selection bias
may arise. However, we think it unlikely that the study
results are compromised as home births in Germany were
much less common in the 1990s (and further on) than in
other countries. According to a report from the German
Society of Out of Hospital Midwifery, which used data from
the German Statistical Office, only 2% of all births in
Germany occurred out of hospital (http://www.quag.de/
content/geburtenzahl.htm).
The breastfeeding effect was robust to sensitivity analyses, in which all models were adjusted for parity and for
its period specific interactions with age. However, no
substantial changes were found in respect to the age

123

P. Rzehak et al.

specific effects of breastfeeding on any outcome (data not

shown).
The development of underweight over time would certainly be of additional interest for the present study and
could in principle be performed by using the 10th and 3rd
percentiles of the new WHO-Growth charts for BMI as cutpoints. However, as the study population consists of healthy full-term neonates with an inclusion criteria of
C2,500 g at birth, we failed to include lower birth weight
newborns by design. Consequently, the lower tail of the
relative weight distribution has a restricted generalizability,
which undermines such an endeavor.
In addition, it would be worthwhile to investigate
whether prenatal development, maternal overweight or
lifestyle and genetic disposition are more important for
birth weight and postnatal development [22, 33, 34].
However, a full life-course epidemiological approach is
beyond the scope of this paper [35]. Nevertheless, one
might speculate that our results of an early developing gap
regarding overweight and obesity between breastfed and
formula fed children, which does not vanish up to age
6 years, are in line with the Early origins of adult disease hypothesis and emphasizes the role of nutrition and
potential metabolic programming. Whether this weight
difference tracks into adolescence and adulthood may be
investigated in the next years as GINI and LISA are
ongoing birth cohort studies.
This study has several strengths. The large number of
anthropometric measurements, in particular in the first
2 years of life and the statistical model allowing for several
period-specific growth rates, subject specific growth trajectories and correlations between period specific velocities,
enabling a more appropriate analysis than those conducted in
most studies. Moreover, the impact of breastfeeding on
period-specific growth velocities has, to our knowledge,
been investigated unspecifically as an overall contrast or
interaction effect with age, but not regarding specific time
windows [7, 8, 10]. Thus, the reported analyses add to a
better understanding of the early developmental process and
the influence of breastfeeding in particular.

Conclusions
Early infancy may be critical for later weight and overweight development and longitudinal analyses should
therefore allow for several period-specific slopes to capture
a better approximation of the true trajectories of growth.
Infants fully-breastfed for at least 4 months gain less
weight, but grow equally in length in the first 12 months of
life than mixed or formula-fed children. The protective
effect of breastfeeding regarding weight and overweight

Period-specific growth rates and breastfeeding

development is therefore related to its modifying effect

regarding weight-gain in early infancy. However, prenatal
factors like fetal development have to be incorporated in a
more elaborated model of life course epidemiology to
further strengthen these results. Nevertheless, as the protective effect of breastfeeding regarding overweight and
obesity lasts at least up to the age of 6 years, breastfeeding
is clearly recommended, whenever possible.
Acknowledgments We thank the families for participation in the
studies; the obstetric units for allowing recruitment, the GINI and
LISA study teams for excellent work and several funding agencies
listed below. Personal and financial support by the Munich Center of
Health Sciences which contributed to this research is gratefully
acknowledged. This work was also supported by the Kompetenznetz
Adipositas (Competence Network for Adipositas) funded by the
Federal Ministry of Education and Research (FKZ: 01GI0826). In
addition, we gratefully acknowledge the editorial work of Elaina
MacIntyre. The GINI Intervention study was funded for 3 years by
grants of the Federal Ministry for Education, Science, Research and
Technology (Grant No. 01 EE 9401-4), the 6 years follow-up of the
GINI-plus study was partly funded by the Federal Ministry of Environment (IUF, FKZ 20462296). The LISA-plus study was funded by
grants of the Federal Ministry for Education, Science, Research and
Technology (Grant No. 01 E.G 9705/2 and 01EG9732) and the
6 years follow-up of the LISA-plus study was partly funded by the
Federal Ministry of Environment (IUF, FKS 20462296). Personal and
financial support by the Munich Center of Health Sciences which
contributed to this research is gratefully acknowledged. This work
was also supported by the Kompetenznetz Adipositas (Competence
Network for Adipositas) funded by the Federal Ministry of Education and Research (FKZ: 01GI0826).

Appendix

Detailed information on statistical analysis

Piecewise linear random coefficient models were applied to
assess growth trajectories and velocities between 03, 36,
612, 1224 months and beyond the 24th month. These
models allow the longitudinal data structure to be
accounted for by including subject specific random effects
and a nonlinear age effect can be modeled by the piecewise
linear functions (polynomial splines). Such longitudinal
models are described in detail in the books of Singer et al.
and Fitzmaurice et al. [18, 19]. We used four knots at 3, 6,
12 and 24 months to connect the slopes of the five time
segments. The choice of the knots was based on the literature, in which different time windows for rapid weight
gain are discussed [2326]. To account for the known sex
specific difference in birth weight and length we included a
main effect for sex in each model.
Formally, the basic piecewise linear random coefficient
model at hand (Model A) can be expressed as follows:

459

Yij ; b0i b1i Ageij b2i Ageij  3 b3i Ageij  6

b4i Ageij  12 b5i Ageij  24 b6 boyi
eij gijA eij

where Yij is the respective continuous outcome (i.e. length,

weight or BMI) for child i at measurement j and Ageij is
age since birth, coded in months, for each child i at measurement j (calculated from the exact age in days). The
term (Ageij - c)? with knots c [ {3, 6, 12, 24} is equal to
(Ageij - c) if Ageij [ c and equal to 0 if Ageij \ c. The
effects bki for k = 0,,5 consist each of a population
averaged fixed effect bk and a subject specific random
effect uki, as given by: b0i b0 u0i ; b1i b1 u1i ; b2i
b2 u2i ; b3i b3 u3i ; b4i b4 u4i and b5i b5 u5i .
Hence, a subject specific intercept u0i as well as five subject
specific slopes u1i,, u5i are estimated. The subject specific random effects vectors ui = (u0i,,u5i)T are assumed
to be mutually independent for all i and normally distributed with zero mean and a covariance matrix R,
i.e. ui * N (0, R). The diagonal of R contains the coefficient specific variances r2k for k = 0,,5. The error terms
eij are also assumed to be normally distributed and identical
and mutually independent for all i, j, i.e. eij * N (0, r2e )
i.i.d. In addition, they are considered as independent from
the random effects. The short notation gijA in [1] stands for
the predictor of Model A and is introduced by reason of
comparability between the different models.
As for interpretation for the regression coefficients, 1
can be regarded as the population baseline velocity of
change for the respective outcome and hence, u1i is the
subject specific deviation from this population baseline. The
term (Ageij - 3)? represents the time since the age of
3 months until measurement j of child i, consequently 2
represents the population based deviation from the slope 1
in the following time period and u2i stands for the associated
individual deviation. For all other knots the coding and
interpretation is analog. Thus, each child can have his own
baseline value at birth and a child specific slope or linear
trajectory in each time period, which yields to a subject
specific non-linear growth pattern by the cumulative combination of the several linear growth estimates. The growth
rate GR at the age period k [ {03, 36, 612, 1224, 24
72} months is thus the cumulative period specific sum of the
estimated regression coefficients, for the first three periods
it can be expressed as follows: GR(0  3 3  b1 ;
GR(0  6 6  b1 3  b2 ; GR(6  12 12  b1 9
b2 6  b3 :
To ease interpretation and to spare the reader the trouble
of calculation we do not report the single slope coefficients
in the result section but we do report the calculated absolute growth rates (velocities) of the outcome per month in
the respective time period (Tables 2, 4). The subject

123

460

P. Rzehak et al.

specific variation of the intercept terms (initial status at

birth) and of the period specific growth rates (rate of
change per month in period) are expressed as 95%-reference ranges and listed in Table 3. A reference range is the
range in which 95% of the estimated subject-specific
intercepts or slopes (here for the calculated growth rates)
^ 1.96 9 estimated standard
are located, formally: b
k
deviation of the subject specific estimates u^ik (square root
^2k ). Note that if the
of the estimated random effect variance r
growth rate is a combination of several slopes (e.g. for
period 36 months, which is calculated as the sum of the
slopes in period 03 and 36), then the standard deviation
is calculated as the square root of the sum of the respective
variances of the slopes and the sum of two times the
respective covariances of these random effects.
To what extent individual initial status of the outcome at
birth and individual change rates co-vary between the
different time windows is expressed as correlations
(derived from the estimated random effects covariance
^ and is listed in the lower part of Table 3. We
matrix R)
report these subject specific variations of growth rates only
for weight and length because for the models regarding
BMI, overweight and obesity development no reliable
random variation in growth rates (beyond the intercept
term) could be estimated.
For the dichotomous outcomes of overweight and
obesity generalized random coefficient models with logitlink function were applied. Therefore the outcome Yij was
assumed to follow a binomial distribution with probability
pij, i.e. Yij * B (1, pij). Hence, the model (Model A) can
be expressed as follows:
pij EYij =gijA

1
1 expgijA

where Yij is a dichotomous outcome (i.e. overweight or

obesity) and gijA is the predictor as in [1]. Since they are
easier to interpret, we report probabilities in Table 4 of the
result section (instead of using logarithmic odds).
In Tables 2 and 3 of the result section there are three
models for each outcome presented. The respective Model
A has already been introduced in [1] and [2], depending on
the outcome. It gives estimates for the baseline value
(initial status) of the outcome and the time period specific
velocities (absolute change of the outcome per month in the
respective period) for the five time segments with sex as
the only covariate. Model B aims at investigating the
influence of breast feeding on the rates of change for the
five time periods by including a main effect for breastfeeding (BF) as well as interaction effects with the piecewise linear terms. Formally, Model B can be obtained by
replacing the predictor gijA of Model A in Eqs. 1 and 2 by
gijB, as given by:

123

gijB gijA b7i Ageij  BFi b8i Ageij  3  BFi

b9i Ageij  6  BFi b10i Ageij  12
 BFi b11i Ageij  24  BFi b12 BFi :

In the result section we do not show the single

interaction estimates but report the absolute growth rates
for the breastfed and for the other children in two different
columns. These interaction effects allow an evaluation as
to whether breastfeeding influences the velocities of
growth in the different time windows.
Model C accounts for the potential confounding effects
of maternal smoking in pregnancy (Smoke), study center
(Center) and socio-economic status (SES) in addition to the
breastfeeding Model B by adjusting for the respective
number of dummy coded categorical variables. Hence, the
predictor for Model C can be expressed as follows:
gijC gijB Smokei SESi Centeri :

Descriptive analyses were conducted by the statistical

software SAS, version 9.1.3 [36]. All longitudinal analyses
were performed with the special purpose software for
multilevel modeling MLwiN, version 2.02 [37]. (Tables 5,
6, 7 and 8).

GINI-plus study group

Institute of Epidemiology, Helmholtz Zentrum MuenchenGerman Research Center for Environmental Health, Neuherberg (Wichmann HE, Heinrich J, Schoetzau A, Popescu
M, Mosetter M, Schindler J, Franke K, Laubereau B,
Sausenthaler S, Thaqi A, Zirngibl A, Zutavern A, Filipiak
B, Gehring U); Department of Pediatrics, Marien-Hospital,
Wesel (Berdel D, von Berg A, Albrecht B, Baumgart A,
Bollrath C, Buttner S, Diekamp S, Gro I, Jakob T, Klemke
K, Kurpiun S, Mollemann M, Neususs J, Varhelyi A, Zorn
C); Ludwig Maximilians University of Munich, Dr. von
Hauner Childrens Hospital (Koletzko S, Reinhard D,
Weigand H, Antonie I, Baumler-Merl B, Tasch C, Gohlert
R, Sonnichsen C); Clinic and Polyclinic for Child and
Adolescent Medicine, University Hospital rechts der Isar of
the Technical University Munich (Bauer CP, Grubl A,
Bartels P, Brockow I, Hoffmann U, Lotzbeyer F, Mayrl R,
Negele K, Schill E-M, Wolf B); IUF-Environmental Health
Research Institute, Dusseldorf (Kramer U, Link E, Sugiri
D, Ranft U).

LISA-plus study group

Institute of Epidemiology, Helmholtz Zentrum MuenchenGerman Research Center for Environmental Health,

BF 9 Age 12?

BF 9 Age 24?

Bad Honnef

Wesel (ref)

[ 10th grade

=10th grade

\10th grade (ref)

Parental education

Leipzig

Munich

Study center

Yes vs. No

Maternal smoking in pregnancy

BF 9 Age 3?

BF 9 Age 6?

BF 9 Age

Breastfeeding 9 Age

C4 vs \4 months

-47.4

Age 24?

Breastfeedingd

3.5

-80.6

1.1

1.9

-232.9

Age 6?

Age 12?

3.1

10.0

7.3

SE

4.8

941.6

203.1

3,262.0

Model A

Weight (g)

-392.7

Age 3?

Age

Age in months

Boy vs. Girl

Gender of infant

Intercept

Initial status at birth

Fixed effects

-44.95

-42.79

-67.04

-81.91

307.81

20.39

446.60

z-value

-16.4

27.6

79.4

-75.6

-17.9

64.6

-38.6

-95.4

-274.8

-353.2

951.5

205.8

3,224.0

Model B

2.1

3.7

7.0

9.6

6.1

10.6

1.6

2.7

5.1

7.0

4.4

10.1

9.3

SE

-7.77

7.40

11.40

-7.87

-2.92

6.12

-24.88

-35.00

-54.16

-50.56

214.30

20.38

344.92

z-value

-32.2

-7.9

2.1

-37.2

-124.7

-59.5

-16.5

27.6

78.9

-74.8

-18.2

70.4

-38.6

-95.4

-274.9

-353.3

951.7

207.4

3,308.0

Model C

20.0

19.4

26.7

17.4

11.5

14.2

2.1

3.7

7.0

9.6

6.1

11.0

1.6

2.7

5.1

7.0

4.5

10.1

19.7

SE

-1.61

-0.41

0.08

-2.13

-10.82

-4.20

-7.81

7.39

11.30

-7.76

-2.96

6.39

-24.77

-34.88

-54.01

-50.33

212.91

20.64

168.09

z-value

-0.37

-0.27

-0.90

-1.15

3.35

1.32

51.04

Model Aa

0.00

-140.64

-43.48

-68.83

0.01
0.01

-62.95

291.98

28.97

1,412.68

z-value

0.02

0.01

0.05

0.04

SE

Length (cm)

Table 5 Detailed listing of regression coefficients (fixed effects) from which change rates of Table 2 were derived

-0.01

0.03

0.29

-0.31

0.21

-0.36

-0.29

-1.06

-0.99

3.35

1.33

50.93

Model Bb

0.01

0.01

0.02

0.02

0.05

0.00

0.01

0.02

0.02

0.01

0.05

0.04

SE

-2.56

2.66

12.30

-18.13

4.43

-93.92

-31.85

-57.95

-48.57

296.11

29.04

1,139.37

z-value

-0.20

-0.06

-0.13

-1.46

-0.62

-0.33

-0.01

0.03

0.30

-0.31

0.24

-0.36

-0.29

-1.06

-0.98

3.34

1.30

51.55

Model Cc

0.09

0.09

0.12

0.08

0.05

0.06

0.01

0.01

0.02

0.02

0.05

0.00

0.01

0.02

0.02

0.01

0.04

0.09

SE

-2.20

-0.72

-1.10

-18.83

-12.15

-5.26

-2.43

2.49

12.30

-17.93

4.89

-94.14

-31.71

-58.03

-47.17

276.74

29.11

580.13

z-value

Period-specific growth rates and breastfeeding

461

123

123

C4 vs \4 months

BF 9 Age 6?

BF 9 Age 12?

BF 9 Age 24?

Bad Honnef

Wesel (ref)

=10th grade

\10th grade (ref)

18.90

-13.64

0.00

-10.01

-88.97

198.50

14.34

719.13

0.06

-0.03

-0.03

0.09

0.05

-0.10

-0.09

-1.17

1.28

0.33

12.44

0.00

0.01

0.00

0.02

0.00

-7.08

11.54

-13.11

3.71

18.32

-17.97

-8.33

0.01
0.01

-90.38

197.23

14.66

561.37

z-value

0.01

0.01

0.02

0.02

SE

-0.01

-0.01

0.04

0.31

-0.15

0.12

-0.03

0.06

-0.03

0.13

0.05

-0.10

-0.10

-1.15

1.27

0.33

12.45

Model Cc

0.04

0.04

0.06

0.04

0.03

0.03

0.00

0.01

0.00

0.03

0.00

0.01

0.01

0.01

0.01

0.02

0.04

SE

-0.29

-0.18

0.76

8.08

-6.05

3.94

-6.96

11.33

-12.92

5.05

18.18

-17.41

-9.75

-89.38

196.66

15.10

283.99

z-value

Model B is based on the respective Model A, however, supplemented by the main effect of breastfeeding and its interactions with the period specific slopes

Breastfeeding was defined as fully breastfeeding for at least 4 months versus other postnatal feeding practices including formula- or mixed-feeding

Model C is based on the respective Model B adjusted for maternal smoking in pregnancy, study center and socio-economic status

Model A is the respective longitudinal piecewise linear random effects regression model described in detail in the Appendix

[10th grade

Parental education

Leipzig

Munich

Study center

Yes vs. No

Maternal smoking in pregnancy

BF 9 Age

BF 9 Age 3?

Breastfeeding 9 Age

0.04

Breastfeedingd

-0.07

Age 24?

0.00

0.01

-0.10

Age 6?

Age 12?

0.01

0.02

0.02

0.01

1.25

0.31

12.52

z-value

SE

Model Bb

Model Aa

BMI (kg/m2)

-1.14

Age 3?

Age

Age in months

Boy vs. Girl

Gender of infant

Intercept

Initial status at birth

Fixed effects

Table 5 continued

462
P. Rzehak et al.

-1,819

1.21

Age 6?/age 6?

Age 12?/age 12?

Age/age

Age 3?/age 3?

0.75

Intercept/intercept

0.01

0.01

50.75

163.52

0.75

1.21

Estimate

148

271

409

245

347

1,040

512

1,433

1,298

125

254

1,197

966

3,391

1,166

SE

Estimate

z-value

-13.49

-3,516

2,644

2,765

-5,416

-30,780

5,922

-7,967

5,913

3,825

4,502

30,950

35,010

140,700

133,730

Estimate

Model Bb
SE

153

-12.93

6.60

11.92

-16.82

-29.52

12.65

-5.62

4.10

30.90

19.47

25.77

36.40

41.94

114.88

z-value

Model B

Model Aa

Between children (level 2(co)variances)c

Within children (level 1variance)

273

418

248

357

1,054

522

1,435

1,305

127

266

1,209

983

3,367

1,171

SE

BMI (kg/m )

-2,065

Age 12?/age 24?

Random effects

Age 6?/age 12?

-3,527

Age 3?/age 24?

Age 6?/age 24?

2,762

Age 3?/age 12?

2,952

Age 3?/age 6?

-5,997

Age/age 24?

Age/age 12?

-31,110

Age/age 6?

Intercept/age 24?

Age/age 3?

6,608

Intercept/age 12?

Intercept/age 6?

5,350
-8,065

Intercept/age 3?

3,918

Age 24?/age 24?

Intercept/age

Age 6?/age 6?
5,172

31,160

Age 12?/age 12?

35,770

Age 3?/age 3?

141,200

134,476

Estimate

Model A

Weight (g)

Age/age

Intercept/intercept

Between children (level 2(co)variances)c

Within children (level 1variance)

Random effects

Table 6 Random effects of models listed in Table 5

0.01

0.01

SE

-12.27

-13.00

6.46

11.29

-15.62

-29.60

11.56

-5.56

4.56

30.55

17.72

25.86

36.25

41.49

114.65

z-value

50.44

172.71

z-value

-1,822

-3,513

2,576

2,765

-5,353

-31,290

6,024

-7,766

5,443

3,833

4,503

31,520

35,470

137,200

133,719

Estimate

Model C

-12.25

-12.87

6.23

11.20

-15.28

-29.44

11.82

-5.42

4.19

30.49

17.67

25.81

35.99

41.05

114.31

z-value

0.73

1.21

Estimate

Model Cc

149

273

413

247

350

1,063

510

1,434

1,299

126

255

1,221

986

3,342

1,170

SE

0.01

0.01

SE

-0.50

0.81

-0.80

0.50

0.50

4.83

1.95

Estimate

Model Aa

-42.53

50.05

162.46

30.23

-30.14

42.07

43.20

51.79

139.36

z-value

z-value

0.01

0.03

0.03

0.01

0.01

0.09

0.01

SE

Length (cm)

-0.46

0.76

-0.75

0.46

0.47

4.75

4.75

Estimate

Model Bb

0.01

0.03

0.03

0.01

0.01

0.09

0.09

SE

-42.27

29.45

-29.37

41.76

42.94

51.14

51.14

z-value

-0.60

0.93

-0.92

0.60

0.60

4.72

1.90

Estimate

Model Cc

0.01

0.03

0.03

0.02

0.01

0.09

0.01

SE

-40.03

30.09

-30.04

39.70

40.52

50.12

135.86

z-value

Period-specific growth rates and breastfeeding

463

123

123

Intercept/age 6?

Intercept/age 12?

Intercept/age 24?

Age/age 3?

Age/age 6?

Age/age 12?

Age/age 24?

Age 3?/age 6?

Age 3?/age 12?

Age 3?/age 24?

Age 6?/age 12?

Age 6?/age 24?

Age 12?/age 24?

See respective footnotes Table 5

a,b,c

Intercept/age 3?

Intercept/age

Estimate

z-value

Estimate

SE

Model Bb

Model Aa

BMI (kg/m2)

Age 24?/age 24?

Random effects

Table 6 continued

SE

z-value

Estimate

Model Cc

SE

z-value

464
P. Rzehak et al.

BF 9 Age 3?

BF 9 Age 6?

BF 9 Age 12?

BF 9 Age 24?

=10th grade

\10th grade (ref)

-9.16

-4.59

-0.56

0.34

3.75

4.68

-64.28

z-value

-0.024

0.067

-0.046

0.128

-0.039

-0.103

-0.015

-0.005

0.145

0.236

-3.582

Logit

Model B

0.011

0.016

0.010

0.079

0.008

0.017

0.038

0.054

0.029

0.050

0.070

SE

-2.29

4.09

-4.80

1.63

-5.15

-6.03

-0.39

-0.09

5.01

4.72

-50.86

z-value

-0.098

-0.098

-0.007

0.359

-0.299

0.264

-0.024

0.067

-0.046

0.219

-0.039

-0.104

-0.013

0.004

0.144

0.252

-3.512

Logit

Model C

0.098

0.096

0.133

0.083

0.058

0.069

0.011

0.017

0.010

0.081

0.008

0.017

0.039

0.054

0.029

0.050

0.110

SE

-1.00

-1.02

-0.05

4.32

-5.17

3.83

-2.28

4.07

-4.80

2.71

-5.10

-6.03

-0.34

0.08

4.97

4.99

-31.84

z-value

-0.055

-0.048

-0.122

0.139

0.072

0.371

-4.955

Logit

Model Aa

Obesity

0.009

0.027

0.072

0.106

0.056

0.077

0.099

SE

-5.95

-1.77

-1.71

1.32

1.29

4.81

-50.09

z-value

-0.042

0.088

-0.054

0.018

-0.037

-0.086

-0.120

0.116

0.116

0.381

-5.005

Logit

Model Bb

Model B is based on the respective Model A, however, supplemented by the main effect of breastfeeding and its interactions with the period specific slopes

Breastfeeding was defined as fully breastfeeding for at least 4 months versus other postnatal feeding practices including formula- or mixed-feeding

Model C is based on the respective Model B adjusted for maternal smoking in pregnancy, study center and socio-economic status

Model A is based on the respective longitudinal piecewise linear random intercept logistic regression model described in the Appendix

[10th grade

Parental education

Wesel (ref)

Bad Honnef

Leipzig

0.006

Munich

Study center

Yes vs. No

Maternal smoking in pregnancy

BF 9 Age

Breastfeeding 9 Age

C4 vs \4 months

-0.050

Breastfeedingd

Age 24?

0.015

0.038

-0.021

-0.070

Age 6?

0.018

Age 12?

0.054

0.105

0.028

0.050

0.054

SE

Age 3?

0.232

-3.479

Logit

Model A

Overweight

Age

Age in months

Boy vs. Girl

Gender of infant

Intercept

Initial status at birth

Fixed effects

Table 7 Detailed listing of logistic regression coefficients (fixed effects) from which change rates of Table 4 were derived

0.018

0.030

0.018

0.144

0.012

0.029

0.071

0.105

0.057

0.078

0.127

SE

-2.33

2.96

-3.02

0.13

-3.04

-2.91

-1.68

1.10

2.03

4.90

-39.47

z-value

-0.289

-0.331

0.086

0.256

-0.409

0.318

-0.042

0.090

-0.056

0.174

-0.036

-0.090

-0.113

0.105

0.124

0.408

-4.747

Logit

Model Cc

0.144

0.141

0.200

0.127

0.090

0.104

0.018

0.030

0.018

0.147

0.012

0.029

0.071

0.105

0.057

0.079

0.177

SE

-2.01

-2.35

0.43

2.02

-4.56

3.06

-2.33

3.01

-3.13

1.18

-2.93

-3.06

-1.58

0.99

2.15

5.18

-26.79

z-value

Period-specific growth rates and breastfeeding

465

123

P. Rzehak et al.

123

Neuherberg (Wichmann HE, Heinrich J, Bolte G, Belcredi

P, Jacob B, Schoetzau A, Mosetter M, Schindler J, Hohnke
A, Franke K, Laubereau B, Sausenthaler S, Thaqi A,
Zirngibl A, Zutavern A); Department of Pediatrics, University of Leipzig (Borte M, Schulz R, Sierig G, Mirow K,
Gebauer C, Schulze B, Hainich J); Institute for Clinical
Immunology and Transfusion Medicine (Sack U, Emmrich
F); Department of Pediatrics, Marien-Hospital, Wesel (von
Berg A, Schaaf B, Scholten C, Bollrath C, Gro I, Mollemann M); Department of Human Exposure-Research and
Epidemiology, UFZ-Center for Environmental Research
Leipzig-Halle (Herbarth O, Diez U, Rehwagen M, Schlink
U, Franck U, Jorks A, Roder S); Department of Environmental Immunology, UFZ-center for Environmental
Research Leipzig-Halle (Lehmann I, Herberth G, Daegelmann C); Ludwig Maximilians University Munich, Dr. von
Hauner Childrens Hospital, Department of Infectious
Diseases and Immunology (Weiss M, Albert M); FriedrichSchiller-University Jena, Institute for Clinical Immunology
(Fahlbusch B), Institute for Social, Occupational and
Environmental Medicine (Bischof W, Koch A); IUFEnvironmental Health Research Institute, Dusseldorf
(Kramer U, Link E, Ranft U, Schins R); Clinic and Polyclinic for Child and Adolescent Medicine, University
Hospital Rechts der Isar of the Technical University
Munich (Bauer CP, Brockow I, Grubl A); Department of
Dermatology and Allergy Biederstein, Technical University Munich (Ring J, Grosch J, Weidinger S).

0.18 28.25

5.05

0.18 28.72

5.10

0.18 29.02

0.08 35.70

2.663

0.076 35.23

5.12

2.68

References

0.07 35.78
a,b,c

See respective footnotes Table 7

2.65
Intercept/intercept

Within children (level 1variance) 1

Between children (level 2(co)variances)

z-value Estimate SE
z-value Estimate SE
z-value Estimate SE
z-value Estimate SE
z-value Estimate SE
Estimate SE

Model Aa
Model A

Overweight
Random effects

Table 8 Random effects of models listed in Table 7

Model B

Model C

Obesity

Model Bb

Model Cc

z-value

466

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