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Association of caesarean delivery with child adiposity from age 6 weeks to 15 years

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Objectives: o assess associations of caesarean section with body mass from birth through adolescence. Design: ongitudinal birth cohort study, following subjects up to 15 years of age. Setting and participants: Children born in 1991-1992 in Avon, UK who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n=10 219). Outcome measures: Primary outcome: standardized measures of body mass (weight-for length z-scores at 6 weeks, 10 and 20 months; and body mass index (BMI) z-scores at 38 months, 7, 9, 11 and 15 years). Secondary outcome: categorical overweight or obese (BMI: 85th percentile) for age and gender, at 38 months, 7, 9, 11 and 15 years. Results: Of the 10 219 children, 926 (9.06%) were delivered by caesarean section. Those born by caesarean had lower-birth weights than those born vaginally (-46.1 g, 95% confidence interval(CI): 14.6-77.6 g; P=0.004). In mixed multivariable models adjusting for birth weight, gender, parental body mass, family sociodemographics, gestational factors and infant feeding patterns, caesarean delivery was consistently associated with increased adiposity, starting at 6 weeks (+0.11 s.d. units, 95% CI: 0.03-0.18; P=0.005), through age 15 (BMI z-score increment+0.10 s.d. units, 95% CI: 0.001-0.198; P=0.042). By age 11 caesarean-delivered children had 1.83 times the odds of overweight or obesity (95% CI: 1.24-2.70; P=0.002). When the sample was stratified by maternal pre-pregnancy weight, the association among children born of overweight/obese mothers was strong and long-lasting. In contrast, evidence of an association among children born of normal-weight mothers was weak. Conclusion: Cesarean delivery is associated with increased body mass in childhood and adolescence. Research is needed to further characterize the association in children of normal weight women. Additional work is also needed to understand the mechanism underlying the association, which may involve relatively enduring changes in the intestinal microbiome.
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ORIGINAL ARTICLE
Association of caesarean delivery with child adiposity from age
6 weeks to 15 years
J Blustein
1
, T Attina
2
, M Liu
3
, AM Ryan
4
,LMCox
5
, MJ Blaser
6
and L Trasande
7
OBJECTIVES: To assess associations of caesarean section with body mass from birth through adolescence.
DESIGN: Longitudinal birth cohort study, following subjects up to 15 years of age.
SETTING AND PARTICIPANTS: Children born in 1991–1992 in Avon, UK who participated in the Avon Longitudinal Study of
Parents and Children (ALSPAC) (n¼10 219).
OUTCOME MEASURES: Primary outcome: standardized measures of body mass (weight-for length z-scores at 6 weeks, 10 and 20
months; and body mass index (BMI) z-scores at 38 months, 7, 9, 11 and 15 years). Secondary outcome: categorical overweight or
obese (BMI X85th percentile) for age and gender, at 38 months, 7, 9, 11 and 15 years.
RESULTS: Of the 10 219 children, 926 (9.06%) were delivered by caesarean section. Those born by caesarean had lower-birth
weights than those born vaginally ( 46.1 g, 95% confidence interval(CI): 14.6–77.6 g; P¼0.004). In mixed multivariable models
adjusting for birth weight, gender, parental body mass, family sociodemographics, gestational factors and infant feeding patterns,
caesarean delivery was consistently associated with increased adiposity, starting at 6 weeks ( þ0.11 s.d. units, 95% CI: 0.03–0.18;
P¼0.005), through age 15 (BMI z-score increment þ0.10 s.d. units, 95% CI: 0.001–0.198; P¼0.042). By age 11 caesarean-delivered
children had 1.83 times the odds of overweight or obesity (95% CI: 1.24–2.70; P¼0.002). When the sample was stratified by
maternal pre-pregnancy weight, the association among children born of overweight/obese mothers was strong and long-lasting. In
contrast, evidence of an association among children born of normal-weight mothers was weak.
CONCLUSION: Caesarean delivery is associated with increased body mass in childhood and adolescence. Research is needed to
further characterize the association in children of normal weight women. Additional work is also needed to understand the
mechanism underlying the association, which may involve relatively enduring changes in the intestinal microbiome.
International Journal of Obesity advance online publication, 14 May 2013; doi:10.1038/ijo.2013.49
Keywords: childhood obesity; adiposity; caesarean delivery; microbiome; ALSPAC
INTRODUCTION
Caesarean section has enhanced and saved lives of mothers
and infants worldwide, and is growing more prevalent in
developing and middle-income countries. The WHO estimates
that caesarean rates in China are 25.9% and rising, already close to
the US rate of 30.3%. In Brazil, the rate is 45.9%. This growth has
been driven in part by financial incentives to providers,
1–4
as well
as by patient preferences.
5,6
The 2011 UK National Institute of
Health and Clinical Guidelines guideline on caesarean delivery did
not find risk for child health, and noted that women requesting
caesarean section often believe that the procedure is ‘safest for
the baby.’
7
However, evidence suggests that caesarean delivery disrupts the
normal bacterial colonization of the newborn.
8
During vaginal birth,
the fetus is coated by and swallows bacterial strains from the
maternal vaginal and gastrointestinal tracts.
8,9
Children who are
delivered by caesarean section miss this normal source of bacterial
colonization. Their intestines are colonized by microbiota derived
from contact with mothers’ skin, and from other sources.
8
The
resulting differences in colonizing bacterial species for vaginally and
operatively delivered children may persist at least into mid-
childhood.
10–13
In light of evidence that experimentally induced
changes in normal gut microbiota are associated with accelerated
weight gain in laboratory animals, differences in founding microbial
populations could affect adiposity among caesarean-delivered
children.
14
Studies of the association between mode of delivery and
adiposity are challenging, as maternal factors that predispose to
caesarean section also may cause greater childhood body mass. In
addition, post partum behaviours (for example, breastfeeding)
could mediate an association between caesarean delivery and
adiposity. The few extant studies vary in inclusion criteria,
availability of relevant clinical data, source and timing of
information about child body mass, and the outcomes that
are measured.
15–18
A recent meta-analysis found a moderate
association between caesarean delivery and adiposity in
childhood, adolescence and adulthood.
19
However, estimates of
the magnitude of the association were quite variable. Some high-
quality studies found no association, and effect estimates were
lower for high quality studies.
1
Department of Health Policy, Medicine, and Population Health, NYU School of Medicine, NYU/Wagner School of Public Service, New York, NY, USA;
2
Department of Pediatrics,
NYU School of Medicine, New York, NY, USA;
3
Department of Population Health and Environmental Medicine, NYU School of Medicine, New York, NY, USA;
4
Department of Public
Health, Weill-Cornell Medical School, New York, NY, USA;
5
NYU Sackler Institute of Graduate Biomedical Studies, New York, NY, USA;
6
Department of Medicine and Microbiology,
NYU School of Medicine, New York, NY, USA and
7
Department of Pediatrics and Environmental Medicine, NYU School of Medicine, NYU/Wagner School of Public Service, New
York, NY, USA. Correspondence: Dr J Blustein, Department of Health Policy, Medicine, and Population Health, NYU School of Medicine, Wagner School of Public Service, 295
Lafayette St, New York, NY 10012, USA
E-mail: jan.blustein@wagner.nyu.edu
Received 31 October 2012; revised 6 March 2013; accepted 10 March 2013; accepted article preview online 8 April 2013
International Journal of Obesity (2013), 1–7
&
2013 Macmillan Publishers Limited All rights reserved 0307-0565/13
www.nature.com/ijo
In this report, we use objective measures of child height and
weight collected over a span of 15 years in the Avon Longitudinal
Study of Parents and Children (ALSPAC), a study that follows a
large birth cohort. The ALSPAC data resource includes unusually
detailed information on clinical, demographic, social and beha-
vioural characteristics of mothers and children that might be
associated with mode of delivery and childhood obesity.
MATERIALS AND METHODS
Study design, setting and participants
ALSPAC was started as a population-based study of pregnant women living
in Avon, UK with expected dates of delivery in 1991 and 1992. While the
timing of enrolment was variable, 85% of eligible births were captured in an
area that is slightly more affluent than the general UK population.
20
Over
time, data have been collected through review of hospital records, surveys
of parents and children, and clinical and laboratory examination. For this
study, we drew heavily on data abstracted from National Health Service
obstetrical records by ALSPAC’s team of six trained research midwives.
From 14 541 ‘core’ pregnancies, we excluded those that did not result in
a live child at 1 year, non-singleton births, those with missing data on birth
weight, and those contributing no data on child body mass after birth. We
excluded children delivered at o37 weeks of gestation, as they are prone
to caesarean delivery and atypical growth and development. We also
confined our sample to children born of mothers without pre-existing
diabetes, gestational diabetes, glycosuria in pregnancy, pre-existing
hypertension or pre-eclampsia (based upon the research midwives’
reviews of the obstetrical notes) as these conditions are associated with
caesarean delivery and may be associated with increased body mass.
21–23
As shown in the flow chart (Supplementary Exhibit 1) our final analytic
sample included 10219 mother-child pairs. Compared with the full ALSPAC
cohort, sample mothers were more likely to be white and more highly
educated.
Measures
Mode of delivery. Data on caesarean versus vaginal delivery was extracted
from the obstetrical records by the research midwife team. In reviewing
the obstetrical record, the midwife researchers also classified caesarean
deliveries as ‘elective’ if previously scheduled, and ‘emergency’ if not.
Mothers who had been scheduled for elective caesarean but who went
into labour before their scheduled date were classified as having had an
emergency caesarean.
Child body mass. Birth weight was extracted from the medical records
and birth length was measured by an ALSPAC researcher. Subsequently,
weight and length (or height, for older children) was measured by ALSPAC
study personnel (in a random 10% subsample) and abstracted from health
visitor records (in the remainder) at ages 6–8 weeks, 38–44 weeks (mean
10 months), 77–106 weeks (mean 20 months), and 38 months. Comparison
of the two sources showed a high degree of agreement.
24
From age 7
years onward, height and weight were assessed by ALSPAC study
personnel in clinic visits. Height was assessed using a Leicester Height
Measure (Holten Crosswell, Dyfed, UK), and weight measured using Tanita
electronic scales, with children dressed in underwear.
For children up to 2 years of age, we transformed weight-for-length to
standardised z-scores using the WHO Child Health Growth Standards
developed from the 1997 to 2003 Multicentre Growth Reference Study.
25
For children older than 2 years, we transformed body mass index (BMI) to
standardised z-scores using US Centers for Disease Control and Prevention
norms from the year 2000.
26,27
We set body mass values equal to missing
for fewer than 1% of the data points (X5orp5 z-score or s.d.), as those
values were likely to reflect errors in data recording. Our primary outcome
was the age- and gender-standardized continuous measure (weight-for-
length z-score at 6 weeks, 10 months and 20 months; BMI z-score at age 38
months and at 7, 9, 11 and 15 years). The prevalence of obesity (BMI
X95th percentile relative to norms) was quite low in the sample (2.8% at 7
years), and so our secondary outcome was categorical overweight or obese
(BMI X85th percentile for age and gender relative to the CDC norms;
hereinafter ‘overweight/obese’) at 38 months and 7, 9, 11, and 15 years.
Mother’s pre-pregnancy BMI; father’s body mass. Shortly after recruitment
into the study, mothers were sent a postal survey asking for their pre-
pregnancy weight and height. These self-reports have been validated by
ALSPAC investigators against obstetrical records of weight gain trajectory
during pregnancy, and there is a high correlation between the self-reports
and predicted pre-pregnancy weight (r¼0.92).
28
Self-reports of pre-
pregnancy height and weight were transformed to BMI in kg m
2
. Father’s
body mass was also self-reported through postal surveys. Both paternal
and maternal BMI were categorized as normal (o25), overweight (BMI, 25–
29) and obese (BMI X30). In addition, maternal pre-pregnancy BMI was
categorized into sample deciles in the multivariable analyses (see below).
Family sociodemographics. At enrolment, postal surveys elicited social
class (using the UK Office of Population Census and Survey classifica-
tions)
29
and education (as defined by the UK Office of Qualifications and
Examinations Regulation),
30
as well as race, which was reclassified into
white and non-white, in this large white population.
Gestational factors. Maternal age and parity were reported in the same
postal survey, as was first trimester smoking (present or absent).
Gestational weight gain was extracted from obstetrical records by the
research midwife team, using methods described elsewhere
28
and
categorized according to the 2009 US Institute of Medicine (IOM)
recommendations
31
as: less than recommended, within the
recommended range, and more than recommended.
Infant feeding. Feeding patterns were reported by postal survey at 6
months, and classified as ‘still breastfeeding,’ ‘stopped breastfeeding,’ and
‘never breastfed.’ Timing of introduction of solid foods was classified as
‘0–2 months,’ ‘3 months,’ or ‘4–6 months.’
Statistical methods
Analytic approach. We characterized the sample by delivery status and
body mass outcomes over time, and examined the associations between
delivery mode and parental body mass, family sociodemographics,
gestational factors and infant feeding, with w
2
tests of association. We
tested the relationship between delivery mode (caesarean versus vaginal)
and our primary (wfl/BMI z-score) and secondary outcome (overweight/
obese) in mixed multivariable models of the whole sample that included
subject-level random effects, and these fixed effects: birth weight as a
continuous variable, gender, parental body mass (mother’s prenatal BMI in
deciles, father normal weight/overweight/obese; both parents obese);
family sociodemographics (maternal socioeconomic status and maternal
education grouped as described above, white/non-white race); gestational
factors (maternal age grouped as o20, 20–24, 25–29, 30–34, X35; parity
grouped as 0 prior, 1 prior, 2 or more prior pregnancies; presence/absence
of maternal smoking during the 1st trimester; gestational weight gain
below, at or above the Institute of Medicine recommendation, breastfeed-
ing currently, formerly, never and introduction of solid foods at 1–2
months, 3 months, or 4–6 months). Linear random effects models were
used to model wfl/BMI z-score and logistic random effects models were
used to model overweight/obesity.
We used several strategies to control for the association between
maternal adiposity and caesarean delivery risk. In addition to excluding
children born to mothers with risks associated with caesarean delivery
and/or childhood obesity, in our multivariable analysis we tested various
specifications for maternal pre-pregnancy BMI, first with pre-pregnancy
BMI z-score as a continuous variable, and then using BMI deciles. Results
were comparable, and we report models using BMI deciles here. We also
estimated the multivariable models in strata defined by maternal pre-
pregnancy weight: normal (BMI o25) and overweight/obese (BMI X25).
These stratified models were specified identically to the full sample
models, except that they included deciles of maternal pre-pregnancy BMI
within each stratum. As a further test for effect stratification, in full sample
regression analyses, we added interaction terms of delivery mode and
maternal pre-pregnancy BMI (categorized as normal versus overweight/
obese). We did an omnibus test that the sum of the interactions over all
time periods was equal to zero.
Finally, in further analyses, we recategorized delivery mode to three
values: (1) elective caesarean, (2) emergency caesarean, and (3) vaginal
delivery, and re-examined the full sample multivariable associations
between these three modes of delivery and our primary outcome. As
emergency caesarean section is more likely to be done for reasons
unrelated to obesity risk (fetal distress, failure to progress), we
hypothesised that compared with children delivered by elective caesarean
section, those delivered emergently might have lower body mass. Also,
because emergency caesarean may be started after the rupture of
Caesarean delivery and child adiposity
J Blustein et al
2
International Journal of Obesity (2013) 1 – 7 &2013 Macmillan Publishers Limited
membranes (allowing exposure to the maternal bacterial microbiota), we
hypothesised that children born by emergency caesarean might have
body mass intermediate between those delivered vaginally and those
delivered electively.
Approach to missing data. The ALSPAC study has enjoyed extraordinarily
consistent response, due to community outreach and engagement with
families in a region where the population has been quite stable.
20
For the
serial measures of body mass, of the eight longitudinal data points, the
mean number of time points measured was 5.2 per child. Between 40.7
and 86.9 per cent of the sample contributed body mass data at any time
point. There was no association between the propensity to contribute data
and mode of delivery (mean number of data points ¼5.23 for children
delivered vaginally and 5.29 for children delivered by caesarean; P¼0.368).
There was also no association between the propensity to contribute data
at the last time point and mode of delivery (40.7% of those delivered
vaginally contributing at 15 years, versus 40.8% of those delivered by
caesarean; P¼0.941).
For some of the covariates used in our multivariable models, there were
substantial missing data. For example, father’s BMI was missing for 33.4%
of the sample, and maternal social class was missing for 21.4% of cases.
Most other variables were missing in the 5–10% range. Consistent with
prior ALSPAC analyses,
32
we created a missing category for each covariate.
As a test of robustness, we reran our main multivariable analysis with
multiple imputation of the dependent variable, using Stata 12.0 (StataCorp LP,
College Station, TX, USA). Those results were essentially identical to the non-
imputed analysis that we report here.
Human subjects
Ethical approval for the study was obtained from the ALSPAC Ethics and
Law Committee and the Local Research Ethics Committees. Adult subjects
gave informed consent, and children provided verbal assent when of age.
This study was reviewed and approved by the IRBs at both the New York
University Washington Square and Medical School campuses.
RESULTS
The mean birth weight in the sample was 3478 g (s.d., 467), and
926 (9.06%) of the 10 219 children were delivered by caesarean
section. Those born by caesarean delivery had lower-birth weights
than those born vaginally ( 46.1 g, 95% CI: 14.6–77.6 g); there
were no differences in the two groups in weight-for-length z-score
at birth ( 0.296 versus 0.301; P¼0.92). At age 7 years, 16.6% of
the children were overweight or obese, and 2.8% met the criteria
for obesity. In other words, adiposity was relatively rare, relative to
the current prevalence in the US and UK populations. Table 1
shows body mass outcomes and numbers of observations
available at each time point.
Factors associated with mode of delivery
Mode of delivery was associated with several characteristics linked
to childhood obesity (Table 2). Caesarean delivery was somewhat
more common among children whose mothers were overweight or
obese before pregnancy, whose parents were both obese, and non-
white children. Children of older mothers were more likely to have
been delivered by caesarean, as were firstborn children, and
children whose mother’s gestational weight gain exceeded Institute
of Medicine recommendations. Caesarean delivery was associated
with less breastfeeding and less early introduction of solid foods.
Association between mode of delivery and body mass over time
There was a consistent association between mode of delivery and
age- and gender-standardized body mass outcomes over time, in
the multivariable analysis (Figure 1). By 6 weeks of age, children
delivered by caesarean section had significantly higher weight-for-
length z-scores ( þ0.11 s.d. units, 95% CI: 0.03–0.18; P¼0.005), a
difference that was still evident at age 15 (BMI z-score
increment þ0.10 s.d. units, 95% CI: 0.001–0.198; P¼0.047). Esti-
mates for increments at every time point can be found in
Supplementary Exhibit 2A. Caesarean delivery also was associated
with overweight/obesity, with a statistically significant increase
through age 11 (overall sample prevalence of overweight/obese at
11 ¼22.3%; adjusted odds ratio ¼1.83, 95% CI: 1.24–2.70;
P¼0.002; Table 3).
In the multivariable models, factors other than caesarean
delivery were also associated with greater body mass. Although
there was variation across models, associated variables included
higher-birth weight, being born of a young mother, greater
maternal pre-pregnancy BMI, paternal overweight/obese, mater-
nal smoking during the first trimester, less breastfeeding, and
earlier introduction of solid foods (Supplementary Exhibit 2).
Association in strata defined by maternal pre-pregnancy weight
For children of normal weight mothers, the increment in BMI
z-score associated with caesarean delivery was consistently
positively signed but of a qualitatively smaller magnitude than in
the full sample, and generally fell short of statistical significance
(Figure 1). In contrast, for children of overweight/obese mothers,
the association was qualitatively larger and more consistently
statistically significant (Figure 1). The apparent duration of
association was different for the two groups, with children of
overweight/obese mothers showing statistically significant
increases in z-score body mass through age 11 ( þ0.25 s.d. units,
95% CI: 0.08–0. 43; P¼0.005; Figure 1). An omnibus test of
interaction was consistent with a difference in the association
between the two pre-pregnancy weight subgroups (P¼0.004).
Supplementary Exhibit 2A shows z-score increments for each time
point, for the two pre-pregnancy weight strata.
Stratified analysis of the secondary outcome (overweight/
obesity) showed a similar pattern (Table 3). For children of normal
weight mothers, the association was generally positive, but
consistently fell short of statistical significance. Among children
of overweight/obese mothers, the magnitude of the association
was larger and more consistently significant. An omnibus test of
the interaction fell short of statistical significance (P¼0.059).
Elective versus emergency caesarean
Children born by elective caesarean had lower-mean birth weights
than those born by emergency caesarean or vaginal delivery (3360
versus 3488 versus 3482 g, P40.001 for both post-hoc tests of
differences between elective caesarean and other groups; P40.10
Table 1. Characteristics of the sample: delivery mode and body mass
over time
Characteristics n
a
Mean (s.d.) or %
Delivered by caesarean section (%) 10 219 9.06
Emergency caesarean (%) 10 219 5.38
Elective caesarean (%) 10 219 3.68
Birth weight (g) 10 219 3478±467
Weight for length z-score at 6 weeks 8883 0.55±1.23
Weight for length z-score at 10 months 8300 0.46±1.03
Weight for length z-score at 20 months 7650 0.66±1.02
BMI z-score at 38 months 7650 0.47±1.04
BMI z-score at 7 years 6221 0.12±0.95
BMI z-score at 9 years 5811 0.17±0.99
BMI z-score at 11 years 5457 0.19±1.02
BMI z-score at 15 years 4156 0.17±0.91
Overweight/obese at 38 months (%) 7060 30.5
Overweight/obese at 7 years (%) 6221 16.6
Overweight/obese at 9 years (%) 5811 20.6
Overweight/obese at 11 years (%) 5457 22.3
Overweight/obese at 15 years (%) 4156 17.0
Abbreviation: BMI, body mass index.
a
Statistics are derived from subjects
with non-missing data at each time point.
Caesarean delivery and child adiposity
J Blustein et al
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&2013 Macmillan Publishers Limited International Journal of Obesity (2013) 1 – 7
for other differences). However, at birth, electively sectioned
children had greater mean z-score weights-for-length ( 0.166 s.d.
versus 0.386 s.d. versus þ0.301 s.d. for elective caesarean
versus emergency caesarean versus vaginal delivery; P¼0.023
for elective versus emergency section; P40.10 for the other
comparisons).
Table 2. Characteristics of the sample by potential confounders and comparison of subgroups by mode of delivery
Characteristics NAll Vaginal delivery Caesarean delivery P-value*
(n ¼10 219)(n¼9293)(n¼926)
Parental body mass
Mother’s prenatal BMI
Normal 7603 74.4 75.3 65.2 o0.001
Overweight 1397 13.7 13.3 17.2
Obese 477 4.7 4.2 9.4
Missing 742 7.3 7.2 8.2
Father’s BMI
Normal 4362 42.7 42.8 41.8 0.643
Overweight 2109 20.6 20.6 21.9
Obese 335 3.3 3.2 3.7
Missing 3413 33.4 33.5 32.6
Both parents obese
No 6330 61.9 62.0 61.8 0.031
Yes 44 0.4 0.4 1.0
Missing 3845 37.6 37.7 37.3
Family sociodemographics
Maternal SES
I (highest) 480 4.7 4.7 4.5 0.181
II 2542 24.9 24.6 27.2
III 4082 40.0 40.0 39.1
IV 765 7.5 7.5 7.3
V 168 1.6 1.6 2.4
Missing 2182 21.4 21.5 19.4
Education
CSE/vocational 2800 27.4 27.4 27.1 0.530
O level (n¼3380) 3380 33.1 33.3 31.2
A level (n¼2247) 2247 22.0 21.8 23.5
Degree (n¼1308) 1308 12.8 12.8 12.7
Missing (n¼484) 484 4.7 4.7 5.4
Race/ethnicity
White (n¼9481) 9481 92.8 93.0 90.7 0.036
Non-white (n¼210) 210 2.1 2.0 2.8
Missing (n¼528) 528 5.2 5.0 6.5
Gestational factors
Maternal age
o20 407 4.0 4.1 2.6 o0.001
20–24 1764 17.3 17.7 13.2
25–29 4055 39.7 39.9 37.9
30–34 2961 29.0 28.6 32.4
X35 1032 10.1 9.7 13.9
Parity
0 Prior 4309 42.2 41.5 49.0 o0.001
1 Prior 3581 35.0 35.4 31.1
2 Prior 1393 13.6 13.7 12.7
3 or more 556 5.4 5.7 3.4
Missing 380 3.7 3.7 3.8
Maternal smoking 1st trimester
No 7633 74.7 74.6 76.1 0.572
Yes 2376 23.3 23.4 21.9
Missing 210 2.1 2.1 1.9
Gestational weight gain relative to IOM norms
Below IOM norms 3144 30.8 31.1 27.2 o0.001
At IOM norms 3586 35.1 35.1 34.7
Above IOM norms 2418 23.7 22.8 32.4
Missing 1071 10.5 11.0 5.7
Infant feeding
Breastfeeding at 6 months
Still breastfeeding 2713 26.6 27.0 22.6 0.018
Had stopped 4242 41.2 44.3 46.0
Never breastfed 2086 20.5 20.1 18.8
Missing 1178 11.5 11.4 13.1
Timing of introduction of solids
0–2 months 1429 14.0 14.3 10.6 0.013
3 months 5159 50.5 50.3 51.9
4–6 months 2424 23.7 23.7 24.2
Missing 1207 11.8 11.7 13.3
Abbreviations: BMI, body mass index; Social class assessed using the UK Office of Population Census and Survey classifications; Level of education assessed
using the UK Office of Qualifications and Examinations Regulation (see text); IOM, Institute of Medicine. *P-value for w
2
test of association between
characteristic and mode of delivery.
Caesarean delivery and child adiposity
J Blustein et al
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International Journal of Obesity (2013) 1 – 7 &2013 Macmillan Publishers Limited
Figure 2 shows multivariable predicted z-score body mass over
time, when delivery mode was categorized in three values: (1)
elective caesarean, (2) emergency caesarean and (3) vaginal
delivery body mass. For all time periods, z-scores were qualita-
tively lowest for children born vaginally, and for most time
periods, highest for children undergoing elective caesarean (see
Supplementary Exhibit 3 for z-score increments at each time
point).
DISCUSSION
In this sample of full-term children born in the UK in the early
1990s, caesarean delivery was associated with increased body
mass from infancy through adolescence. At birth, children
delivered vaginally were slightly heavier, and there was no
difference in z-score weight-for-length between the two groups.
However, by 6 weeks, those born by caesarean had greater
standardized body mass, and this persisted until age 15, in
analyses adjusted for birth weight, gender, parental body mass,
sociodemographic factors, and a set of gestational factors related
to obesity risk. Overweight/obesity was also more common
among children delivered by caesarean.
Evidence of the association was more robust, qualitatively
greater, and longer lasting among children born of overweight/
obese mothers, compared with children born of normal weight
mothers. The reason for this difference by maternal pre-pregnancy
weight is unclear. The genetic characteristics or gestational
exposures of children of overweight/obese mothers may make
them less able to recover from whatever risk for obesity is
conferred by caesarean delivery. Alternatively, the difference in
the two groups may reflect residual confounding by unmeasured
obesity risk, which could be greater among children born of
overweight/obese mothers. This important question bears further
study.
Strengths and limitations of the study
Our longitudinal design with repeated objective measures of body
mass is comparatively strong, relative to studies using a single
cross section. The greatest limitation is the possibility of
unmeasured confounders that are associated with caesarean
delivery and adiposity in infancy, childhood and adolescence. We
used several strategies to minimize this, but we cannot rule out
the possibility of residual confounding.
Our analysis was also limited by sample size. Our findings
support an association between caesarean section in the
population at large, and among children born of overweight/
obese mothers. However, as we have noted, our conclusions are
more tentative for children of normal weight mothers, among
whom the association appears to be weaker. For those children,
we estimate that we only had a 51% chance of detecting a very
small (0.1 z-score) increment in BMI at age 7.
Missing data pose a third limitation to the study. Subjects were
followed for 15 years, and some subjects invariably missed some
measurement points, which could have introduced bias into our
estimates. However, as we estimate an association (rather than a
prevalence), this may be less of a concern.
33
Also reassuring was
the lack of an association between response propensity and
delivery mode. Finally, we confirmed our main analyses using
multiple imputation, and the associations were essentially
unchanged.
Strengths and limitations in the context of previous studies
Our findings are consistent with the theory that caesarean delivery
leads to increased adiposity, which may be through disruption of
the gut microbiome.
34
Generally, we found that later life adiposity
is least likely among children who are born vaginally, slightly more
likely among those delivered via emergency caesarean, and most
likely among children delivered by elective caesarean. This
gradient corresponds to the likelihood that children were
exposed to maternal vaginal bacteria during birth. However,
when our sample was divided into elective and emergent
caesareans, the numbers become too small to detect differences.
Our finding of a positive association between delivery mode
and adiposity is consistent with a meta-analysis that recently
appeared in this journal. Several of the key studies summarized in
that meta-analysis differ from ours, in terms of the clinical
inclusion criteria, incidence of caesarean section in the sample, the
prevalence of adiposity in the children, and/or the outcomes
reported. Two were high-quality studies that failed to find a
significant association between delivery mode and adiposity. The
first, an analysis of the Danish National Birth Cohort, found no
association between caesarean delivery and overweight at age
Figure 1. Association of delivery mode (caesarean versus vaginal)
and child’s body mass, ages 6 weeks to 15 years. Mean predicted
age- and sex-adjusted z-score weight-for-length (wfl) and BMI for
children born by caesarean section and vaginal delivery. Mean
predicted values are derived from mixed multivariable models, as
described in the text. P-values correspond to a two-tailed test of the
difference of means for the modes of delivery, at each time point.
(a) All children; n¼10 219. (b) Children of normal weight mothers;
n¼7603. (c) Children of overweight/obese mothers; n¼1874. (b,c)
Mothers with missing pre-pregnancy weights do not appear.
Caesarean delivery and child adiposity
J Blustein et al
5
&2013 Macmillan Publishers Limited International Journal of Obesity (2013) 1 – 7
7 years.
15
In the Danish National Birth Cohort cohort, the unadjusted
association with overweight was quite small at age 7 (odds
ratio ¼1.15, 95% CI: 1.02–1.29; P¼0.015) relative to the larger
unadjusted association in our sample (odds ratio ¼1.90, 95%
CI: 1.25–2.90; P¼0.003). This discrepancy could reflect differences
in the body mass distributions in the two populations: the
children in the Danish cohort were extraordinarily lean (Danish
obesity prevalence at 7 years was 1.6% among girls and 1.1%
among boys; in the ALSPAC cohort, 2.8% among all children age 7).
A birth cohort study from Brazil,
16
found a crude association
between delivery mode and obesity that was no longer statistically
significant after adjusting for an array of gestational, and
behavioural factors. However, the outcome for that study, obesity,
was relatively rare in absolute terms (between 7 and 15 per cent,
depending on cohort and time point). Using the more common
outcome of overweight/obese might have yielded a statistically
significant positive association in their sample, as it did in ours. Of
note, when we used obesity as an outcome in our data, our
adjusted findings were quite similar to those from Brazil,
with positive estimates that fell short of statistical significance
(analysis not shown).
Generalizing from this study
The ALSPAC data were collected in an era predating the routine
use of intravenous antibiotic prophylaxis with caesarean delivery.
35
Our analysis of data on administration of antibiotics in labour
showed that under 6% of the ALSPAC mothers who underwent
caesarean received prophylaxis. Early life antibiotic exposure
disrupts the developing intestinal microbiome and causes
increased adiposity in laboratory animals.
14
Two recent studies
have found an association between early antibiotic exposure and
subsequent childhood adiposity.
15,36
As contemporary guidelines
for caesarean delivery recommend IV antibiotics at the time of
incision,
7
under current practices, caesarean section may be doubly
disruptive of microbiome development in the neonate.
The children in our sample were born over two decades ago.
Since then, obesity has increased worldwide, and caesarean
section rates are on the rise. If caesarean delivery is obesogenic
(and not just associated with obesity), then reducing the rate of
elective caesarean sections could be an important strategy for
reducing childhood obesity. While stronger evidence of causality
awaits further detailed clinical studies, that research will likely take
years to complete.
Avenues for future research
The association identified here raises a number of questions. More
detailed study remains, for the children of normal weight mothers.
Further work is needed to assess the association in other
populations, with rigorous control for confounding. Research is
needed to understand the mechanisms that link caesarean
delivery to adiposity. For example, more studies of the differences
in the development of gut microbiota between children delivered
by caesarean and children delivered vaginally should be done.
On the clinical side, the cardiometabolic profiles of children
born by caesarean section should be investigated.
37
Ultimately,
identification of subgroups at high risk for adiposity as a result of
caesarean might help in clinical decision-making regarding
delivery mode, and advice given to prospective parents. In sum,
the evidence presented here — along with work by bench
scientists and epidemiologists — suggests that we look further at
the consequences of caesarean delivery, a mode of birth that has
emerged so recently in the course of human evolution.
CONFLICT OF INTEREST
All authors have completed the Unified Competing Interest form at www.icmje.org/
coi_disclosure.pdf (available on request from the corresponding author) and declare:
all authors had financial support from the NYU Global Public Health Research Fund
Figure 2. Association of delivery mode (elective caesarean versus
emergency caesarean versus vaginal) and body mass, ages 6 weeks
to 15 years. Mean predicted age- and sex-adjusted z-score weight-
for-length (wfl) and BMI for children born by elective caesarean
section, emergency caesarean section and vaginal delivery. Mean
predicted values are derived from mixed multivariable models, as
described in the text. P-values correspond to two-tailed tests of the
difference of means for each of the two modes of caesarean
delivery, versus vaginal delivery, at each time point. The upper value
is for elective caesarean versus vaginal delivery, and the lower value
is for emergency caesarean section.
Table 3. Association between mode of delivery and body mass outcome (Overweight/obese)
Body mass outcome Time period All children Children of normal weight
mothers (BMI o25)
Children of overweight/obese
mothers (BMI X25)
Mode of delivery Mode of delivery Mode of delivery
Caesarean Vaginal Caesarean Vaginal Caesarean Vaginal
Child overweight/obese
(z-BMI X1.04)
38 months 1.29 (0.92, 1.80) 1.00 (ref) 1.02 (0.68, 1.54) 1.00 (ref) 2.13 (1.09, 4.18)* 1.00 (ref )
7 years 1.77 (1.20, 2.62)** 1.00 (ref) 1.36 (0.82, 2.25) 1.00 (ref ) 2.62 (1.27, 5.41)** 1.00 (ref )
9 years 1.49 (1.01, 2.20)* 1.00 (ref ) 1.27 (0.77, 2.10) 1.00 (ref ) 1.62 (0.78, 3.37) 1.00 (ref)
11 years 1.83 (1.24, 2.70)** 1.00 (ref) 1.44 (0.87, 2.36) 1.00 (ref) 2.11 (1.01, 4.39)* 1.00 (ref )
15 years 1.11 (0.70, 1.78) 1.00 (ref) 0.69 (0.36, 1.32) 1.00 (ref) 1.92 (0.84, 4.38) 1.00 (ref )
Abbreviation: BMI, body mass index. *Po0.05; **Po0.10 Odds ratios are derived from multivariable mixed effects models with subject-level random
effects, using logistic regression. Models were run for the outcome ‘child is overweight/obese’, within each of the three groups (all children, children of normal
weight mothers, and children of overweight/obese mothers). Models for all children include birth weight, sex, and the variables listed in Table 1, with maternal
pre-pregnancy BMI z-score in deciles. Models for the two subgroups include the same variables, with maternal BMI z-score decile assigned within
the subgroup.
Caesarean delivery and child adiposity
J Blustein et al
6
International Journal of Obesity (2013) 1 – 7 &2013 Macmillan Publishers Limited
for the submitted work, and MJB/LMK had financial support from the National
Institutes of Health (NIH), as described in the acknolwedgements and the Diane Belfer
Program in Human Microbial Ecology; no financial relationships with any organisa-
tions that might have an interest in the submitted work in the previous 3 years; no
other relationships or activities that could appear to have influenced the submitted
work.
ACKNOWLEDGEMENTS
We are extremely grateful to all the families who took part in this study, the midwives
for their help in recruiting them, and the whole ALSPAC team, which includes
interviewers, computer and laboratory technicians, clerical workers, research
scientists, volunteers, managers, receptionists and nurses. The UK Medical Research
Council, the Wellcome Trust (Grant ref: 092731) and the University of Bristol provide
core support for ALSPAC. Additional financial support was provided through a pilot
grant from the NYU Global Public Health Research Challenge Fund, by NIH grants
RO1DK090989 and 1UL1RR029893, and by the Diane Belfer Program in Human
Microbial Ecology.
DISCLAIMER
This publication is the work of the authors and Drs Blustein and Trasande will
serve as guarantors for the contents of this paper and does not reflect the views
of the ALSPAC executive.
DATA SHARING STATEMENT
The authors were granted access to the ALSPAC data through an agreement
with the University of Bristol, and are not authorized to share data with other
investigators.
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Caesarean delivery and child adiposity
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&2013 Macmillan Publishers Limited International Journal of Obesity (2013) 1 – 7
... This result corroborates other studies that show the association of cesarean birth with overweight in childhood and adolescence. [29][30][31] Using similar statistical methodology in a study with children from a Maya community with almost no exposure to obesogenic environmental factors, Veile and Kramer 18 observed a positive association between CB and BMI up to 5 years of age, especially among children born by cesarean to mothers with high BMIs, with higher BMI zscore for age throughout the evaluated period, and higher weight-for-age at 5 years. In a separate study, Veile et al 19 compared Maya children to the Toba/Qom in Argentina, in sex-specific analyses. ...
... It is important to consider the role of pre-gestational BMI and weight gain during pregnancy on offspring weight outcomes. A British cohort study showed that overweight was more common among CB infants in childhood and adolescence, and this association was even stronger among those born to overweight/obese mothers, suggesting that genetic factors and maternal nutritional status hinder individuals' recovery from the risk for obesity associated with CB. 30 The importance of breastfeeding is also well established in the literature as a protective factor against childhood obesity. 11 Possibly, the inverse association found here, in the bivariate analysis, is because of the way breastfeeding data were collected. ...
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... The effects on white matter remained through at least 3 year of age; thus, while this effect may be transient, these results highlight that birth mode may influence neurodevelopmental outcomes in offspring. Other data point to potential links between birth mode and body composition: One study reported two-fold higher risk for adolescent obesity in children born by C-section in the United Kingdom (Blustein et al., 2013). As recently reviewed by Faúndes et al. (2021), most but not all studies have demonstrated modestly higher odds for childhood or young adult obesity in C-section offspring. ...
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... In a study of 436 pregnancies, Mueller et al. (2015) showed that infants born to mothers who had taken antibiotics in the second and third trimesters had an increased risk of childhood obesity. Infants born by caesarean section lose the opportunity to be colonised with the vaginal and intestinal microbiota of the mother, leaving their intestinal microbiota relatively unbalanced and are subsequently more likely to suffer from celiac disease, asthma, and obesity (Mårild et al., 2012;Ege et al., 2011;Blustein et al., 2013). Collado et al. (2010) evaluated the relationship between the body mass and body mass increase of the mother during pregnancy and infant microbiota. ...
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The aim of the study was to study the pre- and perinatal risk factors for the development of overweight/obesity in the population of children aged 7 to 17 years.A case-control study was conducted in which 210 students participated. The case group included 84 students with a verified diagnosis of overweight/obesity, and the control group - 126 healthy children with normal weight. The results revealed the following statistically significant risk factors for pre- and perinatal risk factors for overweight/obesity: Short-lived (P-0.037) and large families (P-0.000), low education of mothers (P-0.035), eating disorders during pregnancy (P-0.009), gestational pregnancy (P<0.035), cesarean section (P<0.017) and artificial feeding (P-0,024).Knowledge of pre- and perinatal risk factors is important to achieve targeted prevention of overweight/obesity in children.
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In April 2006, the World Health Organization (WHO) released new international growth charts for children aged 0-59 months. Similar to the 2000 CDC growth charts, these charts describe weight for age, length (or stature) for age, weight for length (or stature), and body mass index for age. Whereas the WHO charts are growth standards, describing the growth of healthy children in optimal conditions, the CDC charts are a growth reference, describing how certain children grew in a particular place and time. However, in practice, clinicians use growth charts as standards rather than references. In 2006, CDC, the National Institutes of Health, and the American Academy of Pediatrics convened an expert panel to review scientific evidence and discuss the potential use of the new WHO growth charts in clinical settings in the United States. On the basis of input from this expert panel, CDC recommends that clinicians in the United States use the 2006 WHO international growth charts, rather than the CDC growth charts, for children aged <24 months (available at https://www.cdc.gov/growthcharts). The CDC growth charts should continue to be used for the assessment of growth in persons aged 2-19 years. The recommendation to use the 2006 WHO international growth charts for children aged <24 months is based on several considerations, including the recognition that breastfeeding is the recommended standard for infant feeding. In the WHO charts, the healthy breastfed infant is intended to be the standard against which all other infants are compared; 100% of the reference population of infants were breastfed for 12 months and were predominantly breastfed for at least 4 months. When using the WHO growth charts to screen for possible abnormal or unhealthy growth, use of the 2.3rd and 97.7th percentiles (or ±2 standard deviations) are recommended, rather than the 5th and 95th percentiles. Clinicians should be aware that fewer U.S. children will be identified as underweight using the WHO charts, slower growth among breastfed infants during ages 3-18 months is normal, and gaining weight more rapidly than is indicated on the WHO charts might signal early signs of overweight.
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To describe the association and its magnitude between body mass index category, sex, and cardiovascular disease risk parameters in school aged children in highly developed countries. Systematic review and meta-analysis. Quality of included studies assessed by an adapted version of the Cochrane Collaboration's risk of bias assessment tool. Results of included studies in meta-analysis were pooled and analysed by Review Manager version 5.1. Embase, PubMed, EBSCOHost's cumulative index to nursing and allied health literature, and the Web of Science databases for papers published between January 2000 and December 2011. Healthy children aged 5 to 15 in highly developed countries enrolled in studies done after 1990 and using prospective or retrospective cohort, cross sectional, case-control, or randomised clinical trial designs in school, outpatient, or community settings. Included studies had to report an objective measure of weight and at least one prespecified risk parameter for cardiovascular disease. We included 63 studies of 49 220 children. Studies reported a worsening of risk parameters for cardiovascular disease in overweight and obese participants. Compared with normal weight children, systolic blood pressure was higher by 4.54 mm Hg (99% confidence interval 2.44 to 6.64; n=12 169, eight studies) in overweight children, and by 7.49 mm Hg (3.36 to 11.62; n=8074, 15 studies) in obese children. We found similar associations between groups in diastolic and 24 h ambulatory systolic blood pressure. Obesity adversely affected concentrations of all blood lipids; total cholesterol and triglycerides were 0.15 mmol/L (0.04 to 0.25, n=5072) and 0.26 mmol/L (0.13 to 0.39, n=5138) higher in obese children, respectively. Fasting insulin and insulin resistance were significantly higher in obese participants but not in overweight participants. Obese children had a significant increase in left ventricular mass of 19.12 g (12.66 to 25.59, n=223), compared with normal weight children. Having a body mass index outside the normal range significantly worsens risk parameters for cardiovascular disease in school aged children. This effect, already substantial in overweight children, increases in obesity and could be larger than previously thought. There is a need to establish whether acceptable parameter cut-off levels not considering weight are a valid measure of risk in modern children and whether methods used in their study and reporting should be standardised.
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Aim: To describe the methods used to construct the WHO Child Growth Standards based on length/height, weight and age, and to present resulting growth charts. Methods: The WHO Child Growth Standards were derived from an international sample of healthy breastfed infants and young children raised in environments that do not constrain growth. Rigorous methods of data collection and standardized procedures across study sites yielded very high-quality data. The generation of the standards followed methodical, state-of-the-art statistical methodologies. The Box-Cox power exponential (BCPE) method, with curve smoothing by cubic splines, was used to construct the curves. The BCPE accommodates various kinds of distributions, from normal to skewed or kurtotic, as necessary. A set of diagnostic tools was used to detect possible biases in estimated percentiles or z-score curves. Results: There was wide variability in the degrees of freedom required for the cubic splines to achieve the best model. Except for length/height-for-age, which followed a normal distribution, all other standards needed to model skewness but not kurtosis. Length-for-age and height-for-age standards were constructed by fitting a unique model that reflected the 0.7-cm average difference between these two measurements. The concordance between smoothed percentile curves and empirical percentiles was excellent and free of bias. Percentiles and z-score curves for boys and girls aged 0-60 mo were generated for weight-for-age, length/height-for-age, weight-for-length/h eight (45 to 110 cm and 65 to 120 cm, respectively) and body mass index-for-age. Conclusion: The WHO Child Growth Standards depict normal growth under optimal environmental conditions and can be used to assess children everywhere, regardless of ethnicity, socio-economic status and type of feeding.
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OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on cesarean delivery on maternal request. PARTICIPANTS: A non-U.S. Department of Health and Human Services, nonadvocate 18-member panel representing the fields of obstetrics and gynecology, preventive medicine, biometrics, family planning and reproductive physiology, nurse midwifery, anesthesiology, patient safety, epidemiology, pediatrics, perinatal medicine, urology, urogynecology, general nursing, inner-city public health sciences, law, psychiatry, and health services research. In addition, 18 experts from pertinent fields presented data to the panel and conference audience. EVIDENCE: Presentations by experts and a systematic review of the literature prepared by the RTI International-University of North Carolina Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the federal government. CONCLUSIONS: The magnitude of cesarean delivery on maternal request is difficult to quantify. There is insufficient evidence to evaluate fully the benefits and risks of cesarean delivery on maternal request compared with planned vaginal delivery. Any decision to perform a cesarean delivery on maternal request should be carefully individualized and consistent with ethical principles.
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ALSPAC (The Avon Longitudinal Study of Parents and Children, formerly the Avon Longitudinal Study of Pregnancy and Childhood) was specifically designed to determine ways in which the individual’s genotype combines with environmental pressures to influence health and development. To date, there are comprehensive data on approximately 10 000 children and their parents, from early pregnancy until the children are aged between 8 and 9. The study aims to continue to collect detailed data on the children as they go through puberty noting, in particular, changes in anthropometry, attitudes and behaviour, fitness and other cardiovascular risk factors, bone mineralisation, allergic symptoms and mental health. The study started early during pregnancy and collected very detailed data from the mother and her partner before the child was born. This not only provided accurate data on concurrent features, especially medication, symptoms, diet and lifestyle, attitudes and behaviour, social and environmental features, but was unbiased by parental knowledge of any problems that the child might develop. From the time of the child’s birth many different aspects of the child’s environment have been monitored and a wide range of phenotypic data collected. By virtue of being based in one geographic area, linkage to medical and educational records is relatively simple, and hands-on assessments of children and parents using local facilities has the advantage of high quality control. The comprehensiveness of the ALSPAC approach with a total population sample unselected by disease status, and the availability of parental genotypes, provides an adequate sample for statistical analysis and for avoiding spurious results. The study has an open policy in regard to collaboration within strict confidentiality rules.
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Aim: To describe the methods used to construct the WHO Child Growth Standards based on length/height, weight and age, and to present resulting growth charts. Methods: The WHO Child Growth Standards were derived from an international sample of healthy breastfed infants and young children raised in environments that do not constrain growth. Rigorous methods of data collection and standardized procedures across study sites yielded very high-quality data. The generation of the standards followed methodical, state-of-the-art statistical methodologies. The Box-Cox power exponential (BCPE) method, with curve smoothing by cubic splines, was used to construct the curves. The BCPE accommodates various kinds of distributions, from normal to skewed or kurtotic, as necessary. A set of diagnostic tools was used to detect possible biases in estimated percentiles or z-score curves. Results: There was wide variability in the degrees of freedom required for the cubic splines to achieve the best model. Except for length/height-for-age, which followed a normal distribution, all other standards needed to model skewness but not kurtosis. Length-for-age and height-for-age standards were constructed by fitting a unique model that reflected the 0.7-cm average difference between these two measurements. The concordance between smoothed percentile curves and empirical percentiles was excellent and free of bias. Percentiles and z-score curves for boys and girls aged 0–60 mo were generated for weight-for-age, length/height-for-age, weight-for-length/height (45 to 110 cm and 65 to 120 cm, respectively) and body mass index-for-age.Conclusion: The WHO Child Growth Standards depict normal growth under optimal environmental conditions and can be used to assess children everywhere, regardless of ethnicity, socio-economic status and type of feeding.
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Studies have reported inconsistent results concerning the association of cesarean section with offspring obesity. We performed a systematic review and meta-analysis to examine whether cesarean section increases the risk of later overweight and obesity. Pubmed, Embase and Web of Science were searched using different combinations of two groups of keywords: 'cesarean' and 'overweight/obesity'. Cohort or case-control studies that reported the association of cesarean section with childhood (3-8 years), adolescence (9-18 years) and/or adult (>19 years) overweight/obesity were eligible. Where possible, adjusted risk estimates were pooled using a random effects model; otherwise unadjusted estimates were pooled. Statistical heterogeneity was assessed with I(2) statistics; the values of 25%, 50% and 75% were considered to indicate low, medium and high heterogeneity, respectively. We conducted a subgroup analysis to identify the sources of heterogeneity according to study quality defined on the basis of the Newcastle-Ottawa Scale. In total, two case-control and seven cohort studies were identified for the literature review and 15 separate risk estimates were included in the meta-analysis. The overall pooled odds ratio (OR) of overweight/obesity for offspring delivered by cesarean section compared with those born vaginally was 1.33 (95% confidence interval (CI) 1.19, 1.48; I(2)=63%); the OR was 1.32 (1.15, 1.51) for children, 1.24 (1.00, 1.54) for adolescents and 1.50 (1.02, 2.20) for adults. In subgroup analysis, the overall pooled OR was 1.18 (1.09, 1.27; I(2)=29%) for high-quality studies and 1.78 (1.43, 2.22; I(2)=24%) for medium-quality (P for interaction=0.0005); no low-quality studies were identified. The ORs for children, adolescents and adults all tended to be lower for high-quality studies compared with medium-quality studies. Our results indicated that cesarean section was moderately associated with offspring overweight and obesity. This finding has public health implications, given the increase in cesarean births in many countries.International Journal of Obesity advance online publication, 4 December 2012; doi:10.1038/ijo.2012.195.