Prenatal exposure to organochlorine compounds and neuropsychological
development up to two years of life
Joan Fornsa,b,c,⁎,1, Nerea Lertxundid,e,1, Aritz Aranbarrid,e, Mario Murciac,f, Mireia Gascona,b,c,
David Martineza,b,c, James Grelliera,b,c,g, Aitana Lertxundie,h, Jordi Julveza,b,c,i, Eduardo Fanod,e,
Fernando Goñic,j, Joan O. Grimaltk, Ferran Ballesterc,f,l, Jordi Sunyera,b,c,m, Jesus Ibarluzeae,n
aCentre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
bHospital del Mar Research Institute (IMIM), Barcelona, Spain
cCIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Spain
dFaculty of Psychology, University of the Basque Country UPV/EHU, Donostia, Spain
eHealth Research Institute, Donostia, Spain
fCenter for Public Health Research (CSISP), Valencia, Spain
gDepartment of Epidemiology and Biostatistics, Imperial College, London, UK
hFaculty of Medicine and Dentistry, Basque Country University, San Sebastián, Spain
iDepartment of Environmental Health, Harvard School of Public Health, Boston, MA, USA
jLaboratorio de Salud Pública de Guipúzcoa, San Sebastián, Spain
kDepartment of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Barcelona, Spain
lUniversity of Valencia, Valencia, Spain
mPompeu Fabra University, Barcelona, Spain
nSubdirección de Salud Pública de Gipuzkoa, The Basque Government's Health Department, San Sebastián, Spain
a b s t r a c ta r t i c l e i n f o
Received 21 February 2012
Accepted 14 April 2012
Available online 9 May 2012
Polychlorinated biphenyls (PCB), hexachlorobenzene (HCB), and dichlorodiphenyl dichloroethylene (pp′DDE)
are persistent, bioaccumulative, and toxic environmental pollutants with potential neurotoxic effects. Despite a
growing body of studies investigating the health effects associated with these compounds, their specific effects
on early neuropsychological development remain unclear. We investigated such neuropsychological effects in a
population-based birth cohort based in three regions in Spain (Sabadell, Gipuzkoa, and Valencia) derived from
the INMA [Environment and Childhood] Project. The main analyses in this report were based on 1391 mother–
child pairs with complete information on maternal levels of organochlorine compounds and child
neuropsychological assessment (Bayley Scales of Infant Development) at age 14 months. We found that
prenatal PCB exposure, particularly to congeners 138 and 153, resulted in impairment of psychomotor
development (coefficient=−1.24, 95% confidence interval=−2.41, −0.07), but found no evidence for effects
on cognitive development. Prenatal exposure to pp′DDE or HCB was not associated with early neuropsycho-
logical development. The negative effects of exposure to PCBs on early psychomotor development suggest that
the potential neurotoxic effects of these compounds may be evident even at low doses.
© 2012 Elsevier Ltd. All rights reserved.
Organochlorine compounds (OCs), an important kind of persistent
organic pollutant (POP), include polychlorinated biphenyls (PCBs),
dichlorodiphenyl dichloroethylene (DDE), a metabolite of DDT. These
compounds are widespread in the environment and in human tissues.
Foetuses and newborns are exposed to PCBs and other OCs across the
Ribas-Fito et al., 2001) With the exception of DDT, which is still used in
areas with endemic malaria, the use of OCs has been banned across
much of the world. As such, concentrations have been decreasing over
the past 30 years. However, these compounds are still detectable in the
blood of current generations (Jönsson et al., 2005).
Environment International 45 (2012) 72–77
Abbreviations: (PCB), Polychlorinated biphenyls; (HCB), Hexachlorobenzene; (pp′
DDT), dichlorodiphenyltrichloroethane; (pp′DDE), dichlorodiphenyl dichloroethylene;
INMA, [Environment and Childhood] Project; (OCs), Organochlorine Compounds;
(Coef), Coefficient; (BSID), Bayley Scales of Infant Development; (GC-ECD), gas
chromatography with electron capture detector; (GC-MSD), gas chromatography
coupled to a mass spectrometer detector; (LOD), limits of detection; (LOQ), limits of
⁎ Corresponding author at: Centre for Research in Environmental Epidemiology,
IMIM C. Doctor Aiguader 88, 08003 Barcelona, Spain. Tel.: +34 93 214 73 11; fax: +34
93 214 73 02.
E-mail address: firstname.lastname@example.org (J. Forns).
0160-4120/$ – see front matter © 2012 Elsevier Ltd. All rights reserved.
Contents lists available at SciVerse ScienceDirect
journal homepage: www.elsevier.com/locate/envint
PCBs are mixtures of synthetic organic compounds that have been
widely used as insulators, coolants, and lubricants in electrical
transformers, capacitors, and hydraulic equipment, and as plasticizers
in a variety of plastic and rubber products. Negative effects of PCBs on
early cognitive and psychomotor development in children ranging
from 7 to 30 months have been observed in a number of birth cohort
studies (Park et al., 2009; Ribas-Fitó et al., 2003; Walkowiak et al.,
2001). Nevertheless, these negative results have not been replicated
in other studies of children of similar ages (Boucher et al., 2009;
Daniels et al., 2003; Wilhelm et al., 2008).
DDT is a potent insecticide that was used worldwide for agricultural
and public health purposes from the 1940s until the 1970s. Because of
its toxicity on wildlife and humans, its environmental persistence, and
its concentration in the food supply, its use was prohibited in many
populations worldwide (Eskenazi et al., 2009). Epidemiological studies
in children confirm that pp′DDT, and its most stable metabolite pp′DDE
(Maroni et al., 2000), are neurodevelopmental toxicants that may
disrupt the central nervous system (Eskenazi et al., 2006; Ribas-Fitó et
al., 2006, 2007a; Torres-Sánchez et al., 2007). Regarding HCB, the
evidence is less consistent. In a study of Spanish children, effects have
been found on children's behaviour at 4 years of age. However, this
same study could not detect any effects on motor or cognitive
development (Ribas-Fitó et al., 2003, 2007b).
The aim of the present study is to assess the early neuropsycho-
logical effects of the main OCs in a current newborn cohort study with
low concentrations of OC relative to previous studies done in Spain
and other countries (Govarts et al., 2012; Ibarluzea et al., 2011; Llop
et al., 2010).
2.1. Study design and participants
(INfancia y Medio Ambiente [Environment and Childhood]) Project in
several regions of Spain following a common protocol (Guxens et al.,
2011). This analysis uses the INMA cohorts of Valencia, Sabadell, and
Gipuzkoa established between 2003 and 2008. A total of 2150 eligible
to communicate in Spanish or regional languages, singleton pregnancy,
noassisted conception)wererecruitedduring prenatalvisitsin thefirst
trimester of pregnancy. Women were followed through pregnancy and
children from birth through the second year of life. Participants
provided informed consent and the study was approved by hospital
and institutional ethics committees in each region.
2.2. Neuropsychological testing
Cognitive development of 1801 children was assessed at around
14 months of age (range 11–21 months) using the Bayley Scales of
Infant Development (BSID) (Bayley, 1977). The mental scale con-
sisted of 163 items that assessed age-appropriate cognitive develop-
ment in areas such as performance ability, memory, and first verbal
learning. The psychomotor scale consisted of 81 items assessing fine
and gross motor development. All testing was done in the health care
centre in the presence of the mother, by eight specially trained
psychologists who were blinded to exposure status. To limit inter-
observer variability, we applied a strict protocol, including training
sessions where inter-observer differences were quantified and the
use of three sets of quality controls (inter-observer-reliability-tests).
The inter-rater reliability estimated by intra-class correlation was
0.90 for mental test scores, and 0.91 for psychomotor test scores.
Raw scores were standardized for child's age in days at the time of
testing using a parametric method for the estimation of age-specific
reference intervals. The parameters of the distribution were modelled
as a fractional polynomial function of age and estimated using
maximum likelihood methods. Residuals were then normalized to a
mean of 100 points with a standard deviation of 15 points so as to
homogenize the scales (Guxens et al., 2012).
2.3. Organochlorine compounds exposure measurement
118, 138, 153 and 180) were measured in maternal serum (n=1.811)
extracted from peripheral veins between the 7th and 26th weeks of
pregnancy (median=12.9 weeks). Serum samples were stored in
crystal tubes at −80 °C and analyzed with gas chromatography using
methods described elsewhere (Goñi et al., 2007; Grimalt et al., 2010b;
Vizcaino et al., 2010). Samples collected in Gipuzkoa and Sabadell were
analyzed at the Gipuzkoa Basque Government Laboratory using a
method requiring 500 μl of serum per sample (Goñi et al., 2007). Initial
extraction was performed using 96-well solid-phase extraction disk
plates, followed by clean-up with silica gel/sulphuric acid. Samples
were analysed using gas chromatography with electron capture
detector (GC-ECD). Gas chromatography coupled to a mass spectrom-
eter detector (GC–MSD) was used for quantitative and qualitative
confirmation. The overall relative standard deviation (precision) of the
analytical techniques was b15% for OCs and PCBs.
Samples collected in Valencia were analyzed at the Centro
Superior de Investigación (Barcelona) using a method where
compounds were liquid–liquid extracted with hexane from 1 ml of
serum (Goñi et al., 2007) and extracts were cleaned up with sulphuric
acid prior to quantification by GC-ECD (Grimalt et al., 2010b).
Quantitative and qualitative confirmation was performed by gas
chromatography coupled to negative ion chemical ionization mass
spectrometry. Precision, measured as relative standard deviation, was
b14% for all the compounds.
Both laboratories were in compliance with the Arctic Monitoring
and Assessment Program (AMAP) Ring Test Proficiency Program for
persistent organic pollutants in human serum (Centre de Toxicologie,
Institut National de Santé Publique du Québec). Limits of detection
(LOD) were 0.071 ng/ml for Sabadell and Gipuzkoa samples and
between 0.010 and 0.071 ng/ml for Valencia sera. For comparison
purposes, values in Valencia below 0.071 ng/ml were considered as
non-detected. Samples with non-detectable levels were then set at a
value of half the LOD.
PCBs 28, 52, and 101 are not described, as more than 95% of
individuals had levels below the limits of quantification (LOQ). PCB
118 was detectable in 23% of samples. Thus, the sum of PCBs (ΣPCBs)
was calculated by summing the concentrations of predominant
congeners: PCB138, 153 and 180. All measurements of OC concen-
trations are expressed in ng/g lipid using the method described
elsewhere (Phillips et al., 1989). Correlations between adjusted and
unadjusted lipid values were high (0.97 for pp′DDE and 0.95 for
ΣPCBs). Concentrations of mercury were also measured because an
interactive effect of PCBs and MeHg has been previously reported
(Grandjean et al., 2001). The analytical procedure has been described
elsewhere (Ramon et al., 2011).
2.4. Other parental and child variables
Information on parental education, social class, use of gas cooking at
home during pregnancy, country of birth (Spain, foreign), age, parity,
maternal alcohol intake, and marital status was obtained through
questionnaires administered during the 1st and 3rd trimesters of
pregnancy. Parental educational level was defined using three catego-
ries: primary or less, secondary school, and university. Maternal social
class based on occupation was derived from the longest-held job
reported during pregnancy or, for those mothers not working during
their pregnancy, thejob mostrecently held. Whensocialclass couldnot
be derived, the last job of the father was used. Nine social class
J. Forns et al. / Environment International 45 (2012) 72–77
categories were created according to the set of National Occupational
Codes-94 and regrouped into three categories: I+II for managers,
manual workers, and IV+V for skilled, semi-skilled and unskilled
manual workers (Domingo-Salvany et al., 2000). Information related to
the child's gestational age, sex, type of delivery (caesarean, other),
anthropometric measures, and Apgar score at birth was obtained from
clinical records. In a subsequent interview at 14 months, data on the
unemployed), nursery attendance, and infections during the previous
months were collected. All questionnaires were administered face-to-
face by trained interviewers.
2.5. Statistical analysis
Multiple imputation of missing values for all socio-demographical
variables was performed on the 1391 subjects for which complete
information of neuropsychological assessment and OCs was available
using chained equations (van Buuren et al., 1999). Ten imputed data
sets were generated and analyzed separately, and the results were
combined using the Rubin's method (Supplementary Tables 1 and 2)
(Royston, 2004). Results did not differ meaningfully from an analysis
of complete cases (Supplementary Table 3).
Levels of OCs were transformed to the log10scale. Multivariate
linear regression models were built for mental and psychomotor test
scores and OCs considering a subset of a priori selected covariates
using a backward selection procedure. Covariates retained in the
model were those showing associations with mental or psychomotor
test scores with p‐values of b0.05 or those whose inclusion resulted
in a change in the regression coefficient of ≥10%. Breastfeeding and
sex (Boix et al., 2011) were assessed as potential effect modifiers by
studying their interaction with the different OCs. In addition, we
fitted a multipollutant model including all three OCs analyzed (DDE,
HCB, and PCBs) in, in order to disentangle which of them has an
effect. All statistical analyses were done using Stata 10.1 (Stata
Corporation, College Station, Texas).
Overall, 2150 pregnant women were recruited during their first trimester of
pregnancy. A total of 2020 (94%) children were enrolled at birth, and 1801 (83%) were
assessed in the second year of life using BSID. We excluded 72 preterm births
(b37 weeks), 12 infants with unknown gestational age, 17 infants with pathologies
including plagiocephaly, and 108 infants that were flagged by psychologists as having
been uncooperative in tests (infants classified as having neurodevelopment assess-
ments of uncertain quality). After these exclusions, our analysis was based on 1391
(64%) mother–child pairs with complete information on neuropsychological devel-
opment assessment and OCs levels. Differences between participants and non-
participants were investigated and those children that were not included had lower
maternal education, higher maternal smoking use, and shorter breastfeeding duration.
Because of the high proportion of samples below the limit of detection (>80%),
levels of pp′DDT were not considered in the analysis. In general, concentrations of HCB
were much lower (43.4 ng/g lipid) than pp′DDE (119.1 ng/g lipid) or ΣPCBs (102.7 ng/g
lipid) (Table 1). Correlation coefficients between different OCs were: 0.28 (pp′DDE and
ΣPCBs), 0.39 (pp′DDE and HCB) and 0.31 (ΣPCBs and HCB), all with p‐values of b0.001
Maternal levels of PCBs were higher in mothers of higher social classes, higher
levels of education, Spanish origin, and whose children were never breastfed (Table 3).
On the other hand, lower social classes, lower levels of education, or being of non-
Spanish origin were related to higher maternal pp′DDE levels. HCB concentrations
were higher in those mothers who reported active smoking during pregnancy, who
never breastfed, and in Spanish mothers.
Table 4 presents the change in mental and psychomotor test scores associated with
a 10-fold increase in OC serum levels. After adjusting for covariates, we did not detect
any association between maternal serum concentrations of OCs and mental test scores.
We found 1.24-point decreases in psychomotor test scores during the second year of
life associated with 10-fold increases in serum levels of total PCBs (Coefficient (Coef)=
−1.24, 95% confidence interval (CI)=−2.41, −0.07). The analysis for individual PCB
congener levels revealed that all coefficients were negative, only PCB138 and 153 being
marginally statistically significant.
The association between pp′DDE and psychomotor test scores was not linear (p-gain
forlinearityb0.10).Forthisreason,pp′DDElevelswere includedinthemodelsasa binary
variable, where the median was used as a cut-off. No associations were found between
DDE orHCBlevelsandpsychomotortest scores.Inthe multipollutantmodel,weobserved
that the association between PCBs levels and psychomotor test scores remained, albeit
with marginal significance (Coef=−1.22, 95%CI=−2.63, 0.19).
We found no heterogeneity among the cohorts as the relationship between OC
concentrations and mental and psychomotor tests scores did not vary among them.
The associations were modified neither by duration of breastfeeding nor sex (data not
shown). Concentrations of Hg in cord blood were not included in the multivariate
models because they did not satisfy the criteria to be considered a potential
confounder (data not shown).
This study provides further evidence that in utero exposure to
PCBs at concentrations below those reported in previous studies is
associated with early psychomotor impairment, but not with
decreased cognitive development. However, the effects of PCBs and
related compounds are small. Prenatal exposure to DDE and HCB did
not have any effect on neuropsychological development by the
second year of life.
Although concentrations of PCBs were much lower than those
reported in previous studies (Boucher et al., 2009; Govarts et al., 2012;
Ibarluzea et al., 2011), our results are in accordance with this literature.
The distribution of the OCs by social class, education, and country of
birth followed the expected pattern (i.e., higher PCBs and HCB, but
lower DDE in higher social class) (Vrijheid et al., 2012). As observed
previously, the mental scale of BSID to assess cognitive assessment was
not able to detect adverse effects of exposure to PCBs (Boucher et al.,
2009). Conversely, and as has already been reported for several other
birth cohort studies (Koopman-Esseboom et al., 1996; Rogan and
Gladen, 1991; Walkowiak et al., 2001; Winneke et al., 1998) the
psychomotor scale wassufficiently sensitive to detectadverse effects of
these compounds on early psychomotor development. In the present
study, larger effects were found for PCB congeners 138 and 153, while a
smaller effect was detected for congener 180.
Correlation between different OCs.
ΣPCB is computed by the sum of congeners 138, 153, and 180 (congener 118 was
excluded by its low detectability).
*** p-valueb0.001 ; ** p-valueb0.01 ; ***p-valueb0.05.
Percentage of samples above the limit of detection (LOD) and concentrations (ng/g
lipid) of PCBs, pp′DDT, pp′DDE, and HCB in the three INMA cohorts (n=1391).
aΣPCB is computed by the sum of congeners 138, 153, and 180 (congener 118 was
excluded by its low detectability).
J. Forns et al. / Environment International 45 (2012) 72–77
One possible mechanism to explain effects of PCB exposure on
early neuropsychological development involves the cerebellum
(Roegge and Schantz, 2006). The cerebellum plays an essential role
not only in motor control (including balance and coordination) but
also in motor learning and cognition. The development of the
cerebellum takes place from the early embryonic period until the
first years of life making this brain area particularly vulnerable to
environmental insults (ten Donkelaar et al., 2003). Animal studies
have revealed that the cerebellum may be more sensitive to the
effects of PCBs than other brain regions, and neurotoxicity may be
induced through altering intracellular calcium signalling (Kodavanti
et al., 1998; Llansola et al., 2010; Sharma et al., 2000). Specific effects
on the cerebellum would justify the results of the BSID psychomotor
test, as this measures a wide range of gross and fine motor skills.
Another mechanism by which PCBs may affect psychomotor devel-
opment is the alteration of thyroid hormone regulation (Roegge and
Schantz, 2006). The thyroid hormone is essential for the growth and
development of brain, the cerebellum in particular (Rodier, 1980).
Deficiency of this hormone during the perinatal period results in
abnormal cerebellar development, as has been well documented in
rodent models (Koibuchi et al., 2003). However, any link between
PCB-induced thyroid dysfunction and PCB-related deficits in neuro-
psychological developmental has not yet been established (Brouwer
et al., 1999).
In this cohort study, we did not find any adverse effects of prenatal
exposure to PCBs on early cognitive development. Recent studies
have postulated that the more clearly negative effects of PCBs on
cognitive development may be focused on executive functions
(Boucher et al., 2009; Govarts et al., 2012; Ibarluzea et al., 2011).
The executive functions broadly encompass a set of cognitive skills
that are responsible for the planning, initiation, sequencing, and
monitoring of complex, goal-directed behaviour (Royall et al., 2002).
Animal studies have reported disturbances in dopamine levels of the
prefrontal cortex in rats prenatally exposed to PCB (Seegal et al.,
2005). If there is a specific effect of PCBs on executive functions, this
has not been detected at early ages because the prefrontal cortex
which is involved to these complex processes is still immature until
mid-to-late adolescence (Toga et al., 2006).
We demonstrated no effects of prenatal levels of pp′DDE and HCB
on early neuropsychological development in children assessed up to
2 years of age. pp′DDE may disrupt the nervous system causing
chemical changes lasting into adulthood (ATSDR, 2002). The potential
mechanism of HCB may interfere with myelination during develop-
ment, alter regional brain concentrations of some neurotransmitters
(such as serotonin, dopamine, and norepinephrine), and produce
oxidative stress (Bleavins et al., 1984; Goldey and Taylor, 1992; Song
et al., 2006). Since negative effects of these compounds on
neuropsychological development have been reported in previous
studies at older ages, especially for pp′DDE, we would recommend
that further studies carry out neuropsychological assessment in older
children, in which the repertoire of cognitive abilities is wider and
Association between mental and psychomotor test scores and OCs.
pp′DDE = dichlorodiphenyldichloroethylene, HCB = hexachlorobenzene, PCBs =
ΣPCB: sum of PCB congeners #138, #153, and #180.
aModels were adjusted for cohort, sex, main caregiver, maternal country of birth,
maternal social class, birth height, gestational age, and duration of any breastfeeding.
bModels were adjusted for cohort, paternal social class, and gestational age.
Coefficients represented change in mental and psychomotor test scores per natural
logarithm (log10) of exposure, unless specified.
cCoefficient associated to pp′DDE levels>120.42 ng/g lipid (Reference: ≤120.42 ng/g
Geometric mean (GM) and 95% Confidence Interval (95%CI)) of the concentrations of pp′DDE, HCB and ΣPCBs (ng/g lipids) by characteristics of the study population (N=1391).
Duration of any breastfeeding
Primary or less
Maternal social class
Maternal smoking during pregnancy
Maternal country of birth
pp′DDE=dichlorodiphenyldichloroethylene, HCB=hexachlorobenzene, PCBs=polychlorinated biphenyls.
J. Forns et al. / Environment International 45 (2012) 72–77
Concentrations of OCs reported in this study are not directly
comparable with those of previous studies because of differences in
biospecimens, laboratory methods, and the congeners contributing to
the summary estimate of OCs concentrations. However, we used the
three higher chlorinated compounds as indicators of the internal PCB
exposure which is in accordance with previous recommendations
(Hansen, 1998). Concentrations of one of the PCB congeners (PCB153)
are within the range of those reported previously (Longnecker et al.,
2003), where median concentrations of PCB 153 in the ten studies
reviewed ranged from 30 to 450 ng/g serum lipid. The median
concentration of maternal serum PCB153 in our study was 44.8 ng/g
serum lipid. In the present study, Hg levels were measured in the same
maternal serum samples. However, we did not find variations in the
coefficients when the Hg levels were included in the final regression
found no interaction between breastfeeding and the association under
investigation, even though breastfeeding represents the largest source
of PCBs in the postnatal period (Bergonzi et al., 2009; Ibarluzea et al.,
2011; Patandin et al., 1997). This finding may suggest a larger effect of
separate the two exposure periods as PCBs in breastmilk were not
A major strength of this study was its large sample size. We
studied a population-based cohort of 1391 children using field staff,
interviewers, laboratory technicians, and project paediatricians, all of
whom were specifically trained for the project. For the neuropsycho-
logical assessments several quality controls were introduced (inter-
observer reliability-tests) and the psychologists who assessed
children with the BSID test received extensive training to this end.
On the other hand, our study was limited by a number of factors.
Although we included a large number of covariates, we were unable
to control for some factors that may directly affect children's
cognition and indirectly affect exposure to OCs, such as the maternal
intelligence, quality of the home environment, nutrition, maternal
postpartum depression or maternal stress during pregnancy. Mea-
surements of OCs were only done in the prenatal period. Further
measurements in cord blood and in breast milk would be very useful
in order to disentangle the effects of postnatal exposure to these
compounds. In the present study we have measured a set of different
PCB congeners (28, 52, 101, 118, 138, 153, and 180) which are found
at relatively high concentrations in humans and wildlife (Grimalt et
al., 2010a). However, a number of other PCB congeners were not
measured and therefore, their presence and any effects on early
neuropsychological development could not be rejected.
In conclusion, the results of the present study suggest that even at
low levels of exposure to PBCs, infants may be at risk of neurodeve-
lopment impairment at early ages. Persistence of the effects of PCBs,
but also the potential effects of other neurotoxicants, such as DDE and
HCB, should be further assessed at later stages of development, when
the phenotypes (cognitive and psychomotor abilities, including
executive function) are fully developed.
This study was funded by grants from Instituto de Salud Carlos III
(Red INMA G03/176 and CB06/02/0041), FIS-FEDER 03/1615, 04/1509,
04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 04/
2018, 09/02311, and 09/00090, 04/1436, and 08/1151, the Conselleria
de Sanitat Generalitat Valenciana, Generalitat de Catalunya—CIRIT
1999SGR 00241, Department of Health of the Basque Government
(2005111093 and 2009111069), the Provincial Government of Gipuz-
koa (DFG06/004 and DFG08/001), and Fundación Roger Torné, and
Gene–environment interaction on Atention Deficit an Hyperactivity
Disorders and Autism Spectrum Disorder in general population birth
cohorts; núm. dajut 09430, la Fundació de la Marató de TV3.
The authors would particularly like to thank all the participants for
their generous collaboration. A full roster of the INMA Project In-
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://
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