Prenatal Exposure to Dichlorodiphenyltrichloroethane and Obesity at 9 Years of Age in the CHAMACOS Study Cohort
Am J Epidemiol.
Original Contribution Prenatal Exposure to Dichlorodiphenyltrichloroethane and Obesity at 9 Years of Age in the CHAMACOS Study Cohort
Marcella Warner ) 0
Amelia Wesselink 0
Kim G. Harley 0
Asa Bradman 0
Katherine Kogut 0
Brenda Eskenazi 0
0 University of California , 1995 University Avenue, Suite 265, Berkeley, CA 94720-7392 (
Initially submitted November 18, 2013; accepted for publication February 17, 2014. In-utero exposure to endocrine-disrupting compounds, including dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenylethylene (DDE), has been hypothesized to increase the risk of obesity later in life. We examined the associations of maternal serum concentrations of DDT and DDE during pregnancy with body mass index, obesity, waist circumference, and percentage of body fat in 9-year-old children (n = 261) in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal birth cohort study in the Salinas Valley, California (2000-2010). We found associations between prenatal exposure to DDT and DDE and several measures of obesity at 9 years of age in boys but not in girls. For example, among boys, 10-fold increases in prenatal DDT and DDE concentrations were associated with increased odds of becoming overweight or obese (for o,p0-DDT, adjusted odds ratio (OR) = 2.5, 95% confidence interval (CI): 1.0, 6.3; for p,p0-DDT, adjusted OR = 2.1, 95% CI: 1.0, 4.5; and for p,p0-DDE, adjusted OR = 1.97, 95% CI: 0.94, 4.13). The odds ratios for girls were nonsignificant. Results were similar for body mass index z score, waist circumference z score, and odds of increased waist circumference but were less consistent for percentage of body fat. The difference by sex persisted after considering pubertal status. These results provide support for the chemical obesogen hypothesis. body mass index; children; dichlorodiphenyldichloroethylene; dichlorodiphenyltrichloroethane; obesity; prenatal exposure
Abbreviations: BMI, body mass index; CHAMACOS, Center for the Health Assessment of Mothers and Children of Salinas; CI,
confidence interval; DDE, dichlorodiphenyldichloroethylene; DDT, dichlorodiphenyltrichloroethane; OR, odds ratio; SD, standard
In-utero exposure to endocrine-disrupting compounds has
been hypothesized to increase the risk of obesity later in life
). Increasing evidence from studies in animals supports
a potential role for endocrine-disrupting compounds, either
directly or indirectly, in the pathogenesis of obesity (
Earlylife exposure might alter development of adipose tissue by
affecting the number, size, and distribution of adipocytes or the
larger regulatory systems involved in weight homeostasis (
Dichlorodiphenyltrichloroethane (DDT) and its
breakdown product dichlorodiphenyldichloroethylene (DDE) are
persistent organic pollutants and known endocrine disruptors
). Experimental studies have shown a link between
exposure DDT and DDE and adipose dysfunction. In vitro,
p,p′-DDT has been shown to alter adipocyte
differentiation, and the effects correlate with changes in expression
of CCAAT-enhancer binding protein-α and peroxisome
proliferator–activated receptor-γ, transcription factors that
are thought to play an important role in adipogenesis (
Likewise, p,p′-DDE has been shown to increase basal free fatty
acid uptake (
). In animal studies, rats fed DDE-contaminated
salmon oil in combination with a high-fat diet developed
abdominal obesity and insulin resistance (
Several longitudinal birth cohort studies have examined
the relationship of prenatal exposure to DDT and DDE with
child growth (
). Positive associations between prenatal
DDT and DDE exposure and body mass index (BMI; weight
(kg)/height (m)2) z score or overweight status have been
reported in birth cohorts in Europe (
) in which the
followup ages ranged from 1 to 7 years, but these associations were
not found in the United States (
) or Mexico (
In Spain, elevated maternal serum DDE concentration was
associated with an increased risk of being overweight (BMI z
score ≥85th percentile) in 518 children at 14 months of age
). DDT was measured but not analyzed because of the low
detection frequency. Additionally, in 138 Belgian children,
higher cord blood DDE levels were associated with an
increased BMI standard deviation score at 3 years of age; DDT
was not measured (
). Among 344 children in Spain, higher
cord blood p,p′-DDT and p,p-DDE levels were
nonmonotonically associated with increased BMI z score and odds
of being overweight (≥85th percentile) at 6.5 years of age,
but associations with p,p′-DDT were limited to boys (
In Mexico, no association was found between maternal
serum DDT or DDE concentrations at delivery and BMI
standard deviation score in 788 male children aged 5–38 months
from Chiapas, where DDT was recently used (
); there was
also no association between maternal serum DDE
concentration and BMI z score at 12 months of age in 253 children from
). In the Collaborative Perinatal Project birth
cohort, which included births that occurred before DDT was
banned in the United States, there was no clear association
between maternal serum DDT and DDE concentrations and
overweight (BMI >90th percentile) or obesity (BMI >97th
percentile) status at 7 years of age, although estimates were
more strongly positive for boys (
Using data from the Center for the Health Assessment of
Mothers and Children of Salinas (CHAMACOS) Study, a
longitudinal birth cohort study in a California agricultural
community, we previously reported no association between
prenatal DDT and DDE exposure and child obesity between
the ages 2 and 7 years, but we did observe a significant trend
toward a positive association as the children aged (
we report results from a subsequent follow-up of the cohort.
Specifically, we examined the relationships of maternal
serum concentrations of o,p′-DDT, p,p′-DDT, and p,p′-DDE
(DDT and DDE) during pregnancy with child body size at 9
years of age, including BMI, waist circumference, percentage
of body fat, and overweight or obese status. We also
examined whether these relationships were modified by child sex
or the onset of puberty.
The CHAMACOS Study is a longitudinal birth cohort
study of environmental exposures and childhood growth
and development. Pregnant women were recruited from
prenatal clinics serving the farmworker population in the Salinas
Valley, California, between October 1999 and October 2000.
Eligible women were at least 18 years of age, at less than 20
weeks of gestation, and English or Spanish speakers who
qualified for government-sponsored health insurance and
planned to deliver at the county hospital. The study was
approved by the institutional review boards at participating
institutions. Before participation, we obtained written informed
consent from all mothers and oral assent from all children
who were 7 years of age or older.
Of the 601 women who were initially enrolled, 527 were
followed through delivery of a singleton live birth that
survived the neonatal period, and 417 provided a serum sample
during pregnancy for DDT and DDE analysis. Complete
follow-up interview and anthropometric measurements
were available for 261 children at 9 years of age.
Details of the study have been published previously (
Briefly, women were interviewed in English or Spanish using
structured questionnaires twice during pregnancy, after
delivery, and when their children were 0.5, 1, 2, 3.5, 5, 7, and 9
years old. During each interview, we collected information
about family sociodemographic characteristics, maternal
characteristics, and pregnancy and medical histories, as well
as child-based developmental milestone, diet, and behavioral
information. At the 9-year visit, clinical Tanner staging was
conducted by trained research staff. Children were considered
to have entered puberty if they were stage 2+ for breast
development for girls or stage 2+ for pubic hair or genital
development for boys.
Children were weighed and measured by trained research
staff at each visit. At the 9-year visit, we measured barefoot
standing height to the nearest 0.1 cm using a stadiometer and
standing weight to the nearest 0.1 kg using a bioimpedence
scale (Tanita TBF-300A Body Composition Analyzer,
Tanita Corporation of America, Inc., Arlington Heights,
Illinois) that also measured percentage of body fat using
“foot-to-foot” bioimpedance technology. The scale was set
to child mode and the manufacturer’s algorithm was used
for calculation of percentage of body fat. We measured
waist circumference to the nearest 0.1 cm by placing a
measuring tape around the abdomen at the level of the iliac crest,
parallel to the floor. Height and waist circumference were
measured in triplicate and averaged for analysis.
Maternal serum samples were collected using
venipuncture at approximately 26 weeks of gestation (n = 242)
or delivery (n = 19). Serum levels of o,p′-DDT, p,p′-DDT,
and p,p′-DDE were measured using isotope dilution gas
chromatography-high resolution mass spectrometry methods
) and reported on a whole-weight basis ( pg/g). Mean
levels of detection for o,p′-DDT, p,p′-DDT, and p,p′-DDE were
1.3 (standard deviation (SD), 0.7), 1.5 (SD, 0.8), and 2.9 (SD,
1.5) pg/g serum, respectively. For nondetectable values, a
serum level of one-half the detection limit was assigned
). Lipid-adjusted values (ng/g) were calculated by
dividing o,p′-DDT, p,p′-DDT, and p,p′-DDE on a whole-weight
basis by total serum lipid content, estimated by enzymatic
determination of triglycerides and total cholesterol (
Lipid-adjusted levels of o,p′-DDT, p,p′-DDT, and p,p′-DDE
were log10-transformed and analyzed as continuous variables.
We calculated age- and sex-specific BMI z scores and
percentiles for each child using 2000 Centers for Disease Control
and Prevention growth charts (
). Children who were in
the 85th percentile of BMI or higher but lower than the
95th percentile were classified as overweight, and children
who were in the 95th percentile or higher were classified as
obese. We calculated age- and sex-specific waist
circumference z scores and percentiles for each child using the National
Health and Nutrition Examination Survey III reference data
for Mexican-American children provided by Stephen Cook
(Stephen Cook, MD, written communication, 2013) (
Children who were in the 90th percentile or higher were
classified as having increased waist circumference and were
considered to be at risk for metabolic syndrome (
All statistical analyses were performed using Stata, version
). For all outcomes, we used generalized additive
models with a 3-degrees-of-freedom cubic spline to evaluate
the shape of the exposure-response curves in the full sample
and in boys and girls separately. None of the digression from
linearity tests were significant (P = 0.15), suggesting that the
relationships were linear. We examined the relation of
maternal serum DDT and DDE concentrations with continuous
outcomes (BMI z score, waist circumference z score, and
percentage of body fat) using multivariable linear regression and
with categorical outcomes (overweight/obese (≥85th vs.
<85th percentile) and increased waist circumference (≥90th
vs. <90th percentile)) using multivariable logistic regression.
We used multinomial logistic regression to examine the
relation of maternal serum DDT and DDE concentrations with
the 3-category weight outcome (obese, overweight, normal
We considered the following variables as potential
covariates. Maternal variables included socioeconomic status,
educational level, marital status, country of birth, years in the
United States at childbirth, age at pregnancy (years),
prepregnancy BMI (determined using self-reported weight and
measured height), weight gain during pregnancy (from medical
records), smoking during pregnancy, and household food
insecurity at the 9-year visit. Child variables included
birthweight, birth order, breastfeeding (any or none), and
behaviors at 9 years of age, including intakes of soda, sweetened
beverages, and fast food and time spent watching television
or playing outside. Covariates were included in the final
models if they changed the coefficient for exposure (log10DDT or
log10DDE) by more than 10%. Final models were adjusted
for maternal time in the United States at birth and
prepregnancy BMI. We considered effect modification by child sex
in all analyses by including a cross-product term between
exposure and sex. To assess the influence of pubertal status on
the sex-stratified relationship between DDT and DDE
exposure and child body size, we analyzed sex-specific models
that included a cross-product term between exposure and
pubertal status. Interaction P values <0.2 were considered
We reanalyzed the final models first excluding 20 children
who had a low birth weight (n = 8) and/or were preterm (n =
19) and then excluded 1 outlier with standardized residuals
greater than 3 or less than −3. We also reran the final models
using inverse probability weights to account for potential bias
due to loss to follow-up (
Tables 1 and 2 present maternal and child characteristics
by child BMI status at 9 years of age. Mothers were on
average 26.3 (SD, 5.1) years of age at delivery, and most were
Latina (98.1%), had lived in the United States for 5 years
or less at birth (52.1%), had not completed high school
(79.3%), and were living at or below the federal poverty
line (69.3%). Nearly two-thirds (64.8%) of mothers were
overweight or obese before pregnancy.
Children were assessed close to their 9th birthday (mean
age = 9.1 (SD, 0.2) years,) and 54.8% were female (Table 2).
At 9 years of age, 37.8% of girls and 11.0% of boys had
entered puberty. Children watched television an average of 2.1
(SD, 1.2) hours per day and played outside an average of 2.1
(SD, 1.5) hours per day. More than 10% of children
consumed 1 or more sodas per day, 77.4% consumed at least 1
sugar-sweetened beverage per day, and 60.8% consumed at
least 1 fast food meal per week.
At 9 years of age, the mean BMI z score was 1.09 (SD,
1.09), with 16.1% of children classified as overweight and
39.9% classified as obese. Mean waist circumference z
score and percentage of body fat for the group were 1.08
(SD, 0.91) and 27.7% (SD, 10.3), respectively. A total of
122 (46.7%) children had increased waist circumference,
and of these, 120 (98%) were also overweight or obese.
As presented in Tables 1 and 2, overweight or obese
children were more likely to have a mother who was obese before
pregnancy (P < 0.01), a mother who smoked during
pregnancy (P = 0.05), and a higher birth weight (P < 0.01).
There was no significant difference in obesity status of
children by maternal sociodemographic indicators. The
association with covariates was similar when other obesity measures
were considered (data not shown).
Maternal serum levels of o,p′-DDT, p,p′-DDT, and
p,p′-DDE at pregnancy were above the detection limit in
96%, 100%, and 100% of samples, respectively. The median
serum levels were 1.2 (interquartile range, 0.7–3.3) ng/g lipid
for o,p′-DDT, 12.1 (interquartile range, 7.6–42.6) ng/g lipid
for p,p′-DDT, and 1,103.6 (interquartile range, 612.6–
2,709.8) ng/g lipid for p,p′-DDE. As reported previously
), maternal DDT and DDE concentrations were higher
in women who were Latina, Mexican-born, less educated,
and more recent immigrants to the United States.
In the full sample, maternal serum DDT and DDE
concentrations were not associated with BMI z score, waist
circumference z score, or percentage of body fat at 9 years of age
(Table 3). However, we observed statistically significant
interactions by sex for several models. Ten-fold increases in
o,p′-DDT and p,p′-DDT concentrations were significantly
positively associated with BMI z score in boys (for o,p′-DDT,
adjusted β = 0.34, 95% confidence interval (CI): 0.08, 0.60; for
p,p′-DDT, adjusted β = 0.23, 95% CI: 0.03, 0.43) but not in
girls (for o,p′-DDT, adjusted β = −0.13, 95% CI: −0.42, 0.16;
for p,p′-DDT, adjusted β = −0.12, 95% CI: −0.38, 0.15) (P for
interaction = 0.02 and 0.03, respectively). A similar pattern
was observed with p,p-DDE, but the association in boys did
not reach significance (P for interaction = 0.15).
DDT was also significantly positively associated with
waist circumference z scores in boys (for o,p′-DDT, adjusted
Child BMI Category at 9 Years of Agea
Normal Overweight Obese
% No. % No. %
44.1 42 16.1 104 39.9
β = 0.30, 95% CI: 0.08, 0.52; for p,p′-DDT, adjusted β =
0.23, 95% CI: 0.07, 0.39), but in girls, the β coefficients
were nonsignificant (P for interaction = 0.03 and 0.04,
respectively). The estimate for p,p′-DDE did not reach
significance in boys, but there was still evidence of effect
modification by sex (P for interaction = 0.13).
For percentage of body fat, there was some evidence of
effect modification by sex for o,p′-DDT and p,p′-DDT (P for
interaction = 0.10 and 0.08, respectively), with
nonsignificant positive associations in boys but not girls (Table 3).
Similarly, maternal serum DDT and DDE concentrations were
not associated with overweight/obese status or increased
)0 )75 e
) .8 9 . lit rs
) –.35 –15 –,6 iton rcne yea
.(44 .(80 .(07 (067 ivae eph t9a
.97 .51 .97 83 rdd t58 .)5 item
2 1 ,6
a e ≤ y
1 d h
n t cy la
a n n p
D M q s
;S t,B fr u
e h ll ,o
an ig c 2
th ew e =
e r n n
o e o (
r v t e
) lo o s g
) 53 h ; a a
.)7 .49 ,12 litrc gae ltae fso
.)(65 –.(260 –.(267 –(485 iynhep IfroM .eag itshw ryae9
.38 .01 .801 289 rdo icB fro leb ta
1 lho ifc I ira ion
ic e BM va is
,d -sp ic r e
T x if f e
c ( t
D se e ts g
;eD fo -sp te inh 0-D
n lie xe tc tc ,p
le t a a p
h en fso x w
te rc r ’s n
o e e r e
) r p h e p
)3 .)6 710 lho th ihg ish se DD
. 2 , ic 85 ro rF itm
0.()301 –.(703 –.(674 –(3162 lynehd thew litene )5o> ftroa ,pp,T
.77 .21 .12 40 iodp lebo rcpe isce gda .ren 0-DD
2 1 ,11 lroh IM th ne issn lidh ,po
c B 5 qu i c r
id a 9 e m 4 fo
e fr f
, s 2 d
E e th ll o 2 e
e e r t
D ta in c s o n
;xD icd IM ith cau le se
e in B w e b r
ind la , se lb ilaa rep
s rm see lb ta v a
s o b ia to a )
a N o r
m . d va the e n
2 0 8
waist circumference in the full sample, but we observed
statistically significant interaction by sex (Table 4). The
association with overweight/obese status was significant for DDT
in boys ( for o,p′-DDT, adjusted OR = 2.51, 95% CI: 1.00,
6.28; for p,p′-DDT, adjusted OR = 2.11, 95% CI: 1.00,
4.46) but not girls (P for interaction = 0.02 and 0.03,
respectively). The estimate for p,p′-DDE did not reach significance
in boys, but there was still evidence of effect modification by
sex (P for interaction = 0.04). When we examined the
association of maternal serum DDT and DDE concentrations with
the 3-category weight outcome (obese, overweight, normal
weight), the results were similar to the dichotomous
outcomes (data not shown). In boys, DDT was also associated
with odds of increased waist circumference ( for o,p′-DDT,
adjusted OR = 1.98, 95% CI: 0.95, 4.11; for p,p′-DDT,
adjusted OR = 2.05, 95% CI: 1.10, 3.82), but this was not the
case in girls (P for interaction = 0.07 and 0.04, respectively).
Figure 1A and 1B show the puberty-stratified relationship
between DDT and DDE exposure and BMI z score in boys
and girls, respectively (see Web Tables 1 and 2, available
at http://aje.oxfordjournals.org/, for adjusted β coefficients
and 95% confidence intervals). In boys, the associations
persisted among boys who had not yet entered puberty; the
number of boys who had entered puberty (n = 13) was too small to
give meaningful results (data not shown). In girls, regardless
of pubertal status, DDT and DDE concentrations were not
associated with any measure of obesity.
In sensitivity analyses, when we repeated the final models
excluding preterm children and/or those with a low birth
weight, excluding 1 outlier, or adjusting for potential bias
due to loss to follow-up, the results did not change materially
(data not shown). The children included in the analysis did
not differ significantly from those who were excluded
because of missing maternal serum DDT and DDE levels or
9-year anthropometric data (data not shown).
This longitudinal birth cohort study of predominantly
Mexican-American children residing in a California
agricultural community provides evidence that in utero exposure to
DDT and DDE may alter the risk for later obesity among
boys. Specifically, we found that higher prenatal DDT
concentrations were significantly associated with increased
BMI z scores, odds of being overweight, waist circumference
z scores, and odds of increased waist circumference at 9 years
of age, but only in boys. Higher prenatal DDE concentrations
were also nonsignificantly associated with increased odds of
being overweight, waist circumference z scores, and odds of
increased waist circumference in boys. Associations with
body fat percentage were less clear. In contrast, prenatal
DDT and DDE concentrations were not associated with any
measure of obesity in girls. These findings persisted after
considering pubertal status.
Prenatal DDT Exposure and Childhood Obesity 1319
Our findings of associations in boys only are consistent
with most (
18, 19, 21
), but not all (
), studies that have
assessed effect modification by sex. Valvi et al. (
) reported a
nonmonotonic increase in the risk of being overweight at 6.5
years of age and cord blood DDT concentration that was
limited to boys. The association was statistically significant for
the second (269–576 ng/g lipid) but not third tertile of
exposure. Mendez et al. (
) reported that maternal DDE levels
(mean 125 ng/g lipid) were more strongly associated with
rapid growth at 14 months of age in boys, although the sex
differences were not statistically significant. In a more highly
exposed population, Cupul-Uicab et al. (
) reported that the
association of maternal p,p′-DDT concentration (median,
1,170 ng/g lipid) with BMI at age 7 years was stronger in boys
than in girls (P for interaction = 0.20). In contrast, Garced
et al. (
) reported no evidence of sex interaction at 12 months
of age; however, exposure levels were lower in their study.
The International Diabetes Federation does not
recommend diagnosing metabolic syndrome in children younger
than 10 years of age, but those who are 6–10 years of age
and in the 90th percentile or higher of waist circumference
for their age and sex are considered at risk for metabolic
). In the CHAMACOS Study, we found positive
associations between prenatal DDT and DDE concentrations
and increased waist circumference in boys at 9 years of age.
This suggests that exposure to DDT and DDE may be
associated with future risk of metabolic syndrome. To our
knowledge, no other epidemiologic studies have investigated the
relation of prenatal DDT and DDE exposure with increased
waist circumference, metabolic syndrome, or its individual
components. However, recent cross-sectional studies in
adults suggested a positive association of DDE with
metabolic syndrome (
). We plan to examine this association
in future follow-up studies of the CHAMACOS cohort.
Although both DDT congeners are estrogenic, o,p′-DDT
has stronger estrogenic activity (
). Only 2 other studies
have examined prenatal o,p′-DDT and p,p′-DDT separately
). Prenatal levels of o,p′-DDT, p,p′-DDT, and
p,p′DDE were not associated with child weight or height z scores
at age 5 years, and there was no evidence of heterogeneity by
sex in the Child Health and Development Studies (36). There
was also no association with BMI at 10–20 years of age in
boys from the Collaborative Perinatal Project (
levels in those studies were considerably higher than in the
present study, and a standardized measure of BMI was not
used. In the CHAMACOS cohort, we observed similar
associations between o,p-DDT and p,p′-DDT concentrations and
child obesity status at 9 years of age, but estimates for o,p′-DDT
were stronger in most cases. Given the high correlation in the
present study between DDT and DDE (r = 0.9), it is difficult
to separate out the individual associations of each compound
Both DDT and DDE have been associated with adipose
dysfunction in experimental studies (
), and given that
DDT, an estrogen agonist, is metabolized into DDE, an
androgen antagonist, multiple mechanisms may be involved.
The sex-specific associations observed seem plausible given
that both estrogenic and antiandrogenic activity play a key
role in adipogenesis during development (
developmental exposure to DDT and DDE could impact weight by
affecting normal weight homeostasis either directly by acting
on adipose cells through differentiation and proliferation or
indirectly via disruption of the endocrine feedback loop
It is unlikely that our finding of sex-specific associations
between prenatal DDT and DDE concentrations and obesity
outcomes is due to differences in pubertal timing. Among
girls, prenatal DDT and DDE concentrations were not
associated with any measure of obesity, regardless of pubertal
status; among boys, DDT and DDE were associated with
measures of obesity even when restricting the sample to those
who were prepubescent. However, given the small number of
boys who had entered puberty, it will be important to follow
the CHAMACOS cohort through puberty to continue to
examine the longitudinal trends in obesity with regard to
inutero exposure to DDT and DDE while considering the
impact of exposure on the adrenal hormone–mediated increase
in weight and the sex steroid–induced pubertal growth spurt.
The present study has several strengths. The CHAMACOS
study is a longitudinal birth cohort study with a long
follow-up period for which considerable information was
collected about potential confounders. The study population
is relatively homogenous with regard to factors such as diet,
breastfeeding, country of origin, and socioeconomic status,
which can reduce uncontrolled confounding. We were able
to measure exposure to o,p′-DDT, p,p′-DDT, and p,p′-DDE
in maternal serum collected during pregnancy. Exposure
levels were high relative to other Mexican Americans, likely
because of the mothers’ recent immigration from Mexico (
but there was a wide range of exposure. We were able to
measure percentage of body fat using bioelectrical impedance,
which is a more direct measure of adiposity, and used a
standardized measure of overweight based on BMI z score, which
facilitates comparison across studies. In addition, we have
measures of pubertal onset using state-of-the-art Tanner staging.
The present study has some limitations. There were 417
mothers who had maternal serum DDT and DDE
measurements during pregnancy, but we had complete
anthropometric data at age 9 years for only 261 children. However, the
prenatal DDT and DDE exposure levels of those with and
without 9-year anthropometric data were not significantly
different. In addition, predictors of maternal levels of o,p′-DDT,
p,p′-DDT, and p,p′-DDE were similar to those reported
previously in the larger group (
), and adjustment for loss to
follow-up using inverse probability weighting did not change
the results substantially. Finally, unlike the other outcome
measures, data on percentage of body fat were not
standardized for age or sex, which may have limited our ability to
observe significant associations.
In summary, we examined the associations of in utero
exposure to o,p′-DDT, p,p′-DDT, and p,p′-DDE with several
measures of obesity in the CHAMACOS cohort at 9 years
of age. We found that higher prenatal DDT and DDE
concentrations were significantly positively associated with BMI,
waist circumference, and overweight or obese status, but
only in boys. In contrast, DDT and DDE were not associated
with any measure of obesity in girls, even after considering
pubertal status. Our results support the hypothesis that
inutero exposure to endocrine-disrupting compounds may
increase risk of obesity later in life.
Author affiliations: Center for Environmental Research
and Children’s Health, School of Public Health, University
of California at Berkeley, Berkeley, California (Marcella
Warner, Amelia Wesselink, Kim G. Harley, Asa Bradman,
Katherine Kogut, Brenda Eskenazi).
This work was supported by grants from the National
Institute of Environmental Health Sciences at the National
Institutes of Health (grants PO1 ES009605 and R01
ES017054), the National Institute for Occupational Safety
and Health (grant RO1 OH007400), and the US
Environmental Protection Agency (grants R82670901 and
Conflict of interest: none declared.
1. Baillie-Hamilton PF . Chemical toxins: a hypothesis to explain the global obesity epidemic . J Altern Complement Med . 2002 ; 8 ( 2 ): 185 - 192 .
2. Diamanti-Kandarakis E , Bourguignon JP , Giudice LC , et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement . Endocrine Rev . 2009 ; 30 ( 4 ): 293 - 342 .
3. Heindel JJ . Endocrine disruptors and the obesity epidemic . Toxicol Sci . 2003 ; 76 ( 2 ): 247 - 249 .
4. Heindel JJ , vom Saal FS . Role of nutrition and environmental endocrine disrupting chemicals during the perinatal period on the aetiology of obesity . Mol Cell Endocrinol . 2009 ; 304 ( 1-2 ): 90 - 96 .
5. Grün F , Blumberg B . Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling . Endocrinology . 2006 ; 147 ( 6 suppl) : S50 - S55 .
6. Newbold RR , Padilla-Banks E , Snyder RJ , et al. Developmental exposure to endocrine disruptors and the obesity epidemic . Reprod Toxicol . 2007 ; 23 ( 3 ): 290 - 296 .
7. Newbold RR , Padilla-Banks E , Jefferson WN . Environmental estrogens and obesity . Mol Cell Endocrinol . 2009 ; 304 ( 1-2 ): 84 - 89 .
8. Casals-Casas C , Desvergne B . Endocrine disruptors: from endocrine to metabolic disruption . Annu Rev Physiol . 2011 ; 73 : 135 - 162 .
9. Swedenborg E , Ruegg J , Makela S , et al. Endocrine disruptive chemicals: mechanisms of action and involvement in metabolic disorders . J Mol Endocrinol . 2009 ; 43 ( 1 ): 1 - 10 .
10. Grün F , Blumberg B . Endocrine disrupters as obesogens . Mol Cell Endocrinol . 2009 ; 304 ( 1-2 ): 19 - 29 .
11. Agency for Toxic Substances and Disease Registry . Toxicological Profile for DDT, DDE and DDD. Atlanta, GA: US Department of Health and Human Services, Public Health Service; 2002 .
12. Moreno-Aliaga MJ , Matsumura F . Effects of 1 , 1 , 1 - trichloro- 2 ,2 -bis( p-chlorophenyl)-ethane ( p,p′-DDT) on 3T3-L1 and 3T3-F442A adipocyte differentiation . Biochem Pharmacol . 2002 ; 63 ( 5 ): 997 - 1007 .
13. Howell G 3rd, Mangum L. Exposure to bioaccumulative organochlorine compounds alters adipogenesis, fatty acid uptake, and adipokine production in NIH3T3-L1 cells . Toxicol In Vitro. 2011 ; 25 ( 1 ): 394 - 402 .
14. Ruzzin J , Petersen R , Meugnier E , et al. Persistent organic pollutant exposure leads to insulin resistance syndrome . Environ Health Perspect . 2010 ; 118 ( 4 ): 465 - 471 .
15. Ibrahim MM , Fjaere E , Lock EJ , et al. Chronic consumption of farmed salmon containing persistent organic pollutants causes insulin resistance and obesity in mice . PLoS One . 2011 ; 6 ( 9 ): e25170 .
16. Cupul-Uicab LA , Hernández-Avila M , Terrazas-Medina EA , et al. Prenatal exposure to the major DDT metabolite 1,1-dichloro-2,2-bis( p-chlorophenyl)ethylene (DDE) and growth in boys from Mexico . Environ Res . 2010 ; 110 ( 6 ): 595 - 603 .
17. Verhulst SL , Nelen V , Hond ED , et al. Intrauterine exposure to environmental pollutants and body mass index during the first 3 years of life . Environ Health Perspect . 2009 ; 117 ( 1 ): 122 - 126 .
18. Valvi D , Mendez MA , Martinez D , et al. Prenatal concentrations of polychlorinated biphenyls, DDE, and DDT and overweight in children: a prospective birth cohort study . Environ Health Perspect . 2012 ; 120 ( 3 ): 451 - 457 .
19. Mendez MA , Garcia-Esteban R , Guxens M , et al. Prenatal organochlorine compound exposure, rapid weight gain, and overweight in infancy . Environ Health Perspect . 2011 ; 119 ( 2 ): 272 - 278 .
20. Garced S , Torres-Sánchez L , Cebrián ME , et al. Prenatal dichlorodiphenyldichloroethylene (DDE) exposure and child growth during the first year of life . Environ Res . 2012 ; 113 : 58 - 62 .
21. Cupul-Uicab LA , Klebanoff MA , Brock JW , et al. Prenatal exposure to persistent organochlorines and childhood obesity in the US Collaborative Perinatal Project . Environ Health Perspect . 2013 ; 121 ( 9 ): 1103 - 1109 .
22. Warner M , Aguilar Schall R , Harley KG , et al. In utero DDT and DDE exposure and obesity status of 7-year-old Mexican-American children in the CHAMACOS cohort . Environ Health Perspect . 2013 ; 121 ( 5 ): 631 - 636 .
23. Eskenazi B , Bradman A , Gladstone EA , et al. CHAMACOS, A longitudinal birth cohort study: lessons from the fields . J Child Health . 2003 ; 1 ( 1 ): 3 - 27 .
24. Barr JR , Maggio VL , Barr DB , et al. New high-resolution mass spectrometric approach for the measurement of polychlorinated biphenyls and organochlorine pesticides in human serum . J Chromatogr B Analyt Technol Biomed Life Sci . 2003 ; 794 ( 1 ): 137 - 148 .
25. Hornung RW , Reed LD . Estimation of average concentration in the presence of nondetectable values . Appl Occup Environ Hyg . 1990 ; 5 ( 1 ): 48 - 51 .
26. Phillips DL , Pirkle JL , Burse VW , et al. Chlorinated hydrocarbon levels in human serum: effects of fasting and feeding . Arch Environ Contam Toxicol . 1989 ; 18 ( 4 ): 495 - 500 .
27. Kuczmarski RJ , Ogden CL , Guo SS , et al. 2000 CDC Growth Charts for the United States: methods and development . Vital Health Stat 11 . 2002 ;(246): 1 - 190 .
28. Cook S , Auinger P , Huang TT . Growth curves for cardio-metabolic risk factors in children and adolescents . J Pediatr . 2009 ; 155 ( 3 ): S6 . e15 - S6 . e26 .
29. Zimmet P , Alberti G , Kaufman F , et al. The metabolic syndrome in children and adolescents . Lancet . 2007 ; 369 ( 9579 ): 2059 - 2061 .
30. Stata Corporation . Stata statistical software, release 11 . College Station, TX: Stata Corporation; 2009 .
31. Hernán MA , Hernández-Díaz S , Robins JM . A structural approach to selection bias . Epidemiology . 2004 ; 15 ( 5 ): 615 - 625 .
32. Bradman AS , Schwartz JM , Fenster L , et al. Factors predicting organochlorine pesticide levels in pregnant Latina women living in a United States agricultural area . J Expo Sci Environ Epidemiol . 2007 ; 17 ( 4 ): 388 - 399 .
33. Lee DH , Steffes MW , Sjödin A , et al. Low dose organochlorine pesticides and polychlorinated biphenyls predict obesity, dyslipidemia, and insulin resistance among people free of diabetes . PLoS One . 2011 ; 6 ( 1 ): e15977 .
34. Lee DH , Lee IK , Porta M , et al. Relationship between serum concentrations of persistent organic pollutants and the prevalence of metabolic syndrome among non-diabetic adults: results from the National Health and Nutrition Examination Survey 1999-2002 . Diabetologia. 2007 ; 50 ( 9 ): 1841 - 1851 .
35. Jusko TA , Koepsell TD , Baker RJ , et al. Maternal DDT exposures in relation to fetal and 5-year growth . Epidemiology . 2006 ; 17 ( 6 ): 692 - 700 .
36. Gladen BC , Klebanoff MA , Hediger ML , et al. Prenatal DDT exposure in relation to anthropometric and pubertal measures in adolescent males . Environ Health Perspect . 2004 ; 112 ( 17 ): 1761 - 1767 .
37. Cooke PS , Naaz A . Role of estrogens in adipocyte development and function . Exp Biol Med (Maywood) . 2004 ; 229 ( 11 ): 1127 - 1135 .
38. Centers for Disease Control and Prevention . 2001 -2002 National Health and Nutrition Examination Survey (NHANES) . Atlanta, GA: National Center for Health Statistics; 2004 .