ORIGINAL ARTICLE
Indoor Air Pollution From Gas Cooking and Infant
Neurodevelopment
Martine Vrijheid,a,b,c David Martinez,a,b,c Inma Aguilera,a,b,c Mariona Bustamante,c,d
Ferran Ballester,c,e,f Marisa Estarlich,c,e,f Ana Fernandez-Somoano,c,g Mònica Guxens,a,b,c
Nerea Lertxundi,h,i M. Dolores Martinez,j Adonina Tardon,c,g and Jordi Sunyera,b,c,k; on behalf of the
INMA Project
Background: Gas cooking is a main source of indoor air pollutants,
including nitrogen dioxide and particles. Because concerns are
emerging for neurodevelopmental effects of air pollutants, we examined the relationship between indoor gas cooking during pregnancy and infant neurodevelopment.
Methods: Pregnant mothers were recruited between 2004 and 2008
to a prospective birth cohort study (INfancia y Medio Ambiente) in
Spain during the first trimester of pregnancy. Third-trimester questionnaires collected information about the use of gas appliances at
home. At age 11 to 22 months, children were assessed for mental
development using the Bayley Scales of Infant Development. Linear
regression models examined the association of gas cooking and standardized mental development scores (n ⫽ 1887 mother– child pairs).
Submitted 1 April 2011; accepted 19 July 2011.
From the aCenter for Research in Environmental Epidemiology (CREAL),
Barcelona, Spain; bHospital del Mar Research Institute (IMIM), Barcelona, Spain; cCIBER Epidemiología y Salud Pública (CIBERESP),
Spain; dGenes and Disease Program, Centre for Genomic Regulation
(CRG), Barcelona, Spain; eEnviroment and Health Area, Center for
Public Health Research (CSISP), Valencia, Spain; fDepartment of Nursing, University of Valencia, Valencia, Spain; gPreventive Medicine and
Public Health, University of Oviedo, Asturias, Spain; hFaculty of Psychology, University of the Basque Country (EHU-UPV), San Sebastián, Spain;
i
Health Research Institute (BIODONOSTIA), San Sebastián, Spain; jDirección de Calidad Ambiental del Departamento de Medio Ambiente del
Gobierno Vasco, Donostia-San Sebastian, Spain; and kFaculty of Health and
Life Sciences, Pompeu Fabra University, Barcelona, Spain.
This study was funded by grants from Spanish Ministry of Health and
Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041,
FIS-PS09/00090, FIS-FEDER 03/1615, FIS-PI04/1436, 04/1509, 04/
1112, 04/1931, 04/2018, 05/1079, 05/1052, 06/1213, 06/0867, 07/0314,
08/1151, 09/02311, 09/02647, 09/02311), Generalitat de CatalunyaCIRIT 1999SGR 00241, Conselleria de Sanitat Generalitat Valenciana,
Universidad de Oviedo, Obra social Cajastur, Department of Health of
the Basque Government (2005111093 and 2009111069), the Provincial
Government of Gipuzkoa (DFG06/004 and DFG08/001), and Fundación
Roger Torné. The authors have no conflicts of interest to declare.
Supplemental digital content is available through direct URL citations
in the HTML and PDF versions of this article (www.epidem.com).
Editors’ note: A commentary on this article appears on page ●●●.
Correspondence: Martine Vrijheid, Centre for Research in Environmental
Epidemiology, Doctor Aiguader, 88, 08003 Barcelona, Spain. E-mail:
mvrijheid@creal.cat.
Copyright © 2011 by Lippincott Williams & Wilkins
ISSN: 1044-3983/12/2301-0001
DOI: 10.1097/EDE.0b013e31823a4023
Epidemiology • Volume 23, Number 1, January 2012
Results: Gas cookers were present in 44% of homes. Gas cooking
was related to a small decrease in the mental development score
compared with use of other cookers (⫺2.5 points 关95% confidence
interval ⫽ ⫺4.0 to ⫺0.9兴) independent of social class, maternal
education, and other measured potential confounders. This decrease
was strongest in children tested after the age of 14 months (⫺3.1
points 关⫺5.1 to ⫺1.1兴) and when gas cooking was combined with
less frequent use of an extractor fan. The negative association with
gas cooking was relatively consistent across strata defined by social
class, education, and other covariates.
Conclusions: This study suggests a small adverse effect of indoor
air pollution from gas cookers on the mental development of young
children.
(Epidemiology 2012;23: 000 – 000)
T
he presence of gas cookers— or gas stoves—inside the
home is common in developed countries (50% to 70%)
and has long been recognized as a main source of indoor air
pollution.1 Gas cooking produces a complex mixture of
volatile organic compounds, sulfur dioxide, particulates, carbon monoxide, carbon dioxide, nitric oxide, and nitrogen
dioxide.2 Of these, nitrogen dioxide (NO2) is the most extensively studied indoor air pollutant.3 Gas cooking is a main
predictor of indoor NO2 concentrations in homes in developed countries, together with cigarette smoking and outdoor
traffic-related NO2.4 – 8 Homes with gas appliances can have
NO2 concentrations twice as high as other homes; concentrations may exceed the WHO guideline for average annual
outdoor NO2 of 40 g/m3.1,3 Gas combustion also produces
particulate matter smaller than 10 m (PM10)9 and ultrafine
particles in the nm range.10 Women and young children are
especially exposed because they spend a larger part of their
day at home and in the kitchen; they may experience more air
pollution from indoor than from outdoor sources.
Air pollution may impair neurodevelopment.11 Air pollution has been implicated as a chronic source of neuroinflammation and oxidative stress that can produce neuropathology and central nervous system diseases.12 Because
maturation of the brain cortex is intensive in the first few
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Epidemiology • Volume 23, Number 1, January 2012
Vrijheid et al
years of life, this period of neurodevelopment may be particularly vulnerable to environmental pollutants.13 Recent studies have observed adverse cognitive and behavioral effects of
perinatal outdoor air pollution,14 –20 and these studies have
raised concerns about similar effects from indoor air pollution. A small birth-cohort study in Menorca, Spain21 was the
first to report a negative association of exposure to gas
appliances and indoor NO2 with general cognition and inattention symptoms in 4-year-old children. These effects were
modified by the Ile105Val polymorphism in the detoxification gene glutathione-S-transferase P1 (GSTP1). Other recent
research has highlighted the potential role of antioxidant and
anti-inflammatory nutrient intake as modifiers of harmful
effects of outdoor air pollution.22–25 Thus, detoxification and
antioxidant factors also require examination in indoor air
pollution studies.
We examined the relationship between exposure to gas
cookers during pregnancy and mental development of children aged 1 to 2 years in a large Spanish birth cohort study
and the role of potential modifying factors.
METHODS
The population-based birth cohort study INMA (INfancia
y Medio Ambiente-Environment and Childhood) recruited
pregnant women from 4 Spanish regions (Asturias; Gipuzkoa, Basque-Country; Sabadell, Catalonia; and Valencia)
between 2004 and 2008.26 Women were enrolled during the
first trimester of pregnancy at the primary health care center
or hospital (depending on the region) if they fulfilled the
following inclusion criteria: age at least 16 years, intention to
give birth in the reference hospital, no problems in communication, singleton pregnancy, and no assisted conception.26
The study was approved by the Hospital Ethics Committees
in the participating regions; participants signed informedconsent forms.
Information was collected by questionnaires in the first
and third trimesters of pregnancy, and when the child was
approximately 6 months and 14 months old. Questions included maternal and paternal education, social class (coding
maternal and paternal occupation according to the International Standard Classification of Occupations-88 system27),
country of birth, maternal health and obstetric history, parity,
medication use, alcohol consumption, and active and passive
cigarette smoking. Breastfeeding practices were reported at
the last 2 time points. Maternal diet during the pregnancy was
assessed through a validated food frequency questionnaire in
trimesters one and three.28 Participation rates at each follow-up
are reported elsewhere in detail26; 54% of eligible women
agreed to participate in the study, and of those, 90% were still
being followed up when the child was 14 months of age.
Women from higher educational levels were somewhat more
likely to participate and to continue participation.26
In one region (Sabadell), we analyzed data on the
child’s GSTP1 Ile105Val polymorphism, which had been
2 | www.epidem.com
found in the previous study in Menorca, to modify the effect
of gas cooking.21 DNA extraction from cord blood was
performed at the Spanish National Genotyping Centre using
the Chemagic Magnetic Separator technology (Chemagen).
DNA samples were quantified using dsDNA fluorescent detection (PicoGreen, Molecular Probes, Eugene, Oregon) and
normalized to 75 to 100 ng/L. GSTP1 Ile105Val polymorphism (rs1695, A/G) was genotyped with KASPar technology (KBioscience, Hoddesdon, UK). GSTP1 Ile105Val genotypes were in Hardy-Weinberg equilibrium.
Gas Cooking
A questionnaire on environmental exposures was administered in person to the mothers during the third trimester
of pregnancy. This questionnaire included questions on age
and size of the home, number of persons resident, type of
cooker used inside the house (natural gas, butane gas, propane gas, electric, other), use of an extractor fan (always,
sometimes, never), type of heating, number of hours per day
when windows were opened for ventilation (by season),
passive smoking in the house, and other indoor and outdoor
environmental exposures. We categorized information on
type of cooker as “gas cooker” (any type of gas cooker) and
“no gas cooker” (electric cooker and other). Validation studies with cohort participants in 2 regions (Sabadell and Valencia) characterized gas cooking as a major determinant of
indoor NO2 concentrations: in subsamples of 108 pregnant
mothers29 and 352 1-year-old children,8 average indoor NO2
concentrations in homes with gas cookers were nearly twice
those in homes with electric cookers, and indoor exposure
correlated well with personal exposure.29
We created further subcategories of gas-cooking exposure by type of gas (natural gas, butane/propane gas), and we
categorized houses with and without gas cookers by use of an
extractor fan (always, sometimes/never) and by ventilation of
the house (⬍2 hours, ⱖ2 hours per day). Literature and
results from our cohort suggest that more NO2 is emitted by
butane and propane gas than by natural gas.8 Also, more
frequent use of extractor fans is expected to reduce indoor
levels of air pollutants from cooking. The net effect of
ventilation is more complex as ventilation may lower exposure from indoor sources but increase exposure from outdoor
sources; these effects are likely to depend on season.8 Very
few subjects (⬍5%) used gas fires or heaters other than
central heating, so we did not analyze exposure from heaters.
Neurodevelopment testing
Children’s neurodevelopment was assessed around 14
months of age (range, 11 to 22 months) using the Bayley
Scales of Infant Development.30 The Bayley mental development scale (163 items) assesses age-appropriate cognitive
development in areas such as performance ability, memory,
and first verbal learning. The Bayley psychomotor scale
consists of 81 items assessing fine and gross motor develop© 2011 Lippincott Williams & Wilkins
Epidemiology • Volume 23, Number 1, January 2012
ment. Because earlier studies found effects of air pollution
mainly on cognitive development,14 –18,20,21 we focused on
the Bayley mental score as the main outcome, and analyzed
psychomotor scores only in a sensitivity analysis. All testing
was done at the primary care center, in the presence of the
mother, by specially trained psychologists who were blind to
any exposure information. The assessments followed a strict
fieldwork protocol, including interobserver reliability tests.
Psychologists flagged children whose Bayley tests were of
poor quality because of basic pathologies (Down syndrome,
autism) or less-than-optimal cooperation of the child (due to
tiredness, bad mood, illness, etc), and these were excluded
from main analyses. The Bayley mental and psychomotor
indices (MDI, PDI) are based on a U.S. reference sample, and
their appropriateness outside the United States has been
questioned.31 In our study population, age of the child still
had an influence on the MDI and PDI. We therefore used our
own population to standardize the raw Bayley scores, based
on the child’s age in days at test administration. Standardized
scores were then computed from the standardized residuals,
under the assumption of a normal distribution with a mean of
100 and a standard deviation (SD) of 15. The correlation
between this standardized score and the MDI was 0.92.
Children born preterm (⬍37 weeks’ gestation) have a particular developmental pattern and were therefore excluded from
the main analysis. Also, the few children tested after 23
months of age were excluded.
Statistical Analysis
Multivariate linear regression models were used to
examine the association of gas cooking with the mental
development score. Regression models always included
child’s sex and region as covariates. We then introduced
maternal education and maternal social class; these 2 variables did not show evidence for collinearity in the model.
Other, covariates were evaluated as potential confounders if
they were reported to be associated with neurodevelopment in
the literature or showed a relationship with gas cooking in our
data. Covariates evaluated were birth weight, gestational age,
season of birth, breastfeeding, nursery attendance, paternal
social class, paternal education, paternal country of birth,
maternal country of birth, maternal age, parity, maternal
smoking at any time during pregnancy, maternal cotinine
concentration (in trimester 3 spot urine samples), presence of
a smoker in the house, alcohol consumption during pregnancy, fish consumption during pregnancy (total of all fish
types), consumption of fruit and vegetables during pregnancy, age of the house, type of house, number of people in
the house, urban or rural area, cord blood mercury concentration, and average outdoor NO2 concentration during the
pregnancy (as estimated from a land use regression model).32
Covariates were retained only if they modified the coefficient
of the gas cooking variable in the basic model by ⬎5%. The
final multivariate model included sex, region, maternal edu© 2011 Lippincott Williams & Wilkins
Gas Cooking and Neurodevelopment
cation, maternal social class, gestational age, maternal country of origin, and type of house. Because information was
missing for some covariates (up to 22%, Table 1) and to
address the potential bias and loss of precision that could
result from incomplete case analyses, we used multiple imputations to replace missing values in covariates. We created
20 imputations, generating 20 complete datasets that we
analyzed following the standard combination rules for multiple
imputations (eTable 1, http://links.lww.com/EDE/A523).33
Neurodevelopment tests of the children were spread
over a relatively wide age range, from 11 to 22 months.
Because it is difficult to compare results in children of very
different ages, we stratified analyses by test age using the
median Bayley test age as cutoff point (⬍14 months, ⱖ14
months or more). We evaluated the robustness of results over
various strata of potential confounding variables. We also
stratified by consumption of antioxidant nutrients (breastfeeding, fish consumption, and fruit and vegetable intake), which
are possible modifiers of air pollution effects as reported in
the literature. In the Sabadell region, we had data on the
child’s GSTP1 Ile105Val polymorphism; we stratified analyses following a genetic dominant model (Ile/Ile vs. Ile/Val
and Val/Val), while restricting to children with parents of
Spanish origin and white ethnic background to limit the
potential for population-stratification bias. The presence of
interactions between gas cooking and stratification variables
was assessed by likelihood ratio tests of the interaction terms
in the regression model. All statistical analyses were conducted with Stata 10.0 statistical software (Stata Corporation,
College Station, TX).
RESULTS
A total of 2644 mother– child pairs were enrolled in the
first trimester; of whom, 2260 (85%) participated in the
Bayley scale testing at 14 months. Of these, 2113 were term
births (ⱖ37 weeks) with a Bayley test before 23 months of
age and thus eligible for this study. Of these, 1887 pairs
(89%) had good quality Bayley test results, and data on gas
cooking (189 were excluded for poor test quality, 16 for
having basic pathologies, and 21 for missing gas cooking
data); they formed the main sample for analysis. The included
mother– child pairs were generally of higher social class and
higher educational achievement than the original cohort of
enrolled mothers (eTable 2, http://links.lww.com/EDE/A523).
Forty-four percent of mothers (n ⫽ 825) reported
having a gas cooker at home in the third trimester of
pregnancy. Of these, most were connected to natural gas
(n ⫽ 583); the rest used propane or butane gas cookers. Of
those who did not use gas cookers, 98% had electric
cookers. Twelve percent of mothers changed cooker status
between the third trimester interview and the time of
neurodevelopment testing of the child.
Mothers with gas cookers were of lower social class
and educational achievement, and were more likely to have
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Epidemiology • Volume 23, Number 1, January 2012
Vrijheid et al
TABLE 1. Summary Measuresa of Covariates by Presence of Gas Cooker in the House,
and Mean Bayley Mental Development Score by Covariate Categories (n ⫽ 1887)
Gas Cooking
Covariates
Child’s sex
Girl
Boy
Birth weight (g); mean (SD)
Gestational age (weeks); mean (SD)
Breastfeeding (months)
⬍6
ⱖ6
Missing
Nursery attendance
Yes
No
Missing
Age at Bayley test administration (months)
⬍14
ⱖ14
Region
Asturias
Gipuzkoa
Sabadell
Valencia
Maternal social class
Professionals and managers (I, II)
Other nonmanual (III)
Skilled, semiskilled, and unskilled manual
(IV, V)
Maternal education
Primary or secondary
High school
University
Missing
Maternal country of birth
Spain
Other
Missing
Parity (no. previous pregnancies)
0
ⱖ1
Missing
Maternal smoking during pregnancy
No
Yes
Missing
Maternal cotinine in urine (ng/mL)
⬍4
4–99.9
ⱖ100
Missing
Yes
(n ⴝ 825)
%
No
(n ⴝ 1062)
%
Mental Score
Mean (SD)
48
52
3293 (433)
39.9 (1.2)
52
48
3302 (414)
39.8 (1.2)
102.0 (14.8)
97.9 (14.8)
—
—
53
46
1
54
43
3
99.3 (14.9)
100.8 (15.1)
29
68
3
36
58
7
100.2 (15.1)
100.0 (14.9)
51
49
31
69
100.2 (15.2)
99.8 (14.8)
8
9
37
47
25
37
18
21
102.0 (15.3)
98.0 (14.9)
99.7 (14.5)
100.6 (15.1)
20
26
54
24
29
47
101.6 (14.4)
100.6 (15.7)
98.9 (14.8)
28
43
29
⬍1
18
41
42
⬍1
99.2 (15.0)
100.0 (14.8)
100.3 (15.2)
87
13
⬍1
96
4
⬍1
100.2 (15.1)
97.2 (13.9)
54
46
⬍1
60
40
0
100.5 (14.9)
99.2 (15.1)
65
35
⬍1
73
27
⬍1
99.9 (15.0)
100.0 (15.0)
34
37
22
8
40
38
15
7
101.0 (14.7)
99.1 (15.1)
100.5 (14.7)
(Continued)
4 | www.epidem.com
© 2011 Lippincott Williams & Wilkins
Epidemiology • Volume 23, Number 1, January 2012
Gas Cooking and Neurodevelopment
TABLE 1. (Continued)
Gas Cooking
Covariates
Yes
(n ⴝ 825)
%
Smoking in the house
No
62
Yes
38
Missing
⬍1
Urban/rural area
Urban
75
Semirural/Rural
25
Missing
Age of the house (years)
⬍15
44
ⱖ15
53
Missing
4
Type of house
Flat
84
Other
16
Missing
⬍1
No. people per room
⬍1
82
ⱖ1
18
Missing
⬍1
Maternal fish consumption (g/day)b
⬍69.6
59
ⱖ69.6
40
Missing
1
Maternal consumption of fruit and vegetables (g/day)b
⬍540.4
55
ⱖ540.4
45
Cord blood mercury (g/L); mean (SD)
11.2 (9.7)
Missing (%)
23
Outdoor NO2 concentration (g/m3)b
⬍29.1
37
ⱖ29.1
60
Missing
3
a
No
(n ⴝ 1062)
%
Mental Score
Mean (SD)
73
27
⬍1
100.3 (15.2)
99.3 (14.6)
89
11
⬍1
100.1 (14.9)
99.4 (15.3)
55
43
2
100.2 (15.0)
99.8 (15.0)
78
21
⬍1
100.0 (14.9)
99.6 (15.5)
88
11
1
100.1 (15.0)
99.1 (15.2)
52
46
2
99.8 (15.0)
100.0 (14.9)
56
45
11.2 (8.3)
22
99.7 (15.1)
100.3 (14.9)
—
67
30
3
99.4 (14.9)
100.4 (14.9)
Values presented as percentages unless otherwise indicated for continuous variables.
Cutoffs defined by mean values.
b
been born outside Spain (Table 1). They also reported
higher levels of smoking, had higher cotinine levels, and
reported more often that cigarette smoking occurred inside
the house. Houses with gas cookers were more likely to be
older (at least 15 years) and less likely to have central
heating and air conditioning than houses without gas
cookers. Houses with gas cookers also had more inhabitants and a higher density of persons per room. Gas cookers
were more prevalent in the eastern Spanish regions of
Sabadell and Valencia (around 63% of houses had gas
cookers) than in the northern regions of Asturias and
Gipuzkoa (18% had gas cookers). Gas cookers were used
more often in areas classified as rural. Mothers living in
© 2011 Lippincott Williams & Wilkins
houses with gas cookers reported lower consumption of
fish, but intake of fruit and vegetables and duration of
breast-feeding were similar to mothers not using gas cookers. Outdoor NO2 levels were higher near houses with gas
cookers; mercury levels in cord blood were similar. Mental
development scores differed by child’s sex, gestational
age, breastfeeding, social class, maternal country of birth,
and region, but not by any of the other covariates (Table 1).
Sex, gestational age, social class, and region had a substantial
effect on mental scores in the final multivariable adjusted
model (eTable 3, http://links.lww.com/EDE/A523).
The presence of a gas cooker in the home was associated
with decreased mental development scores in both the model
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Epidemiology • Volume 23, Number 1, January 2012
Vrijheid et al
TABLE 2.
Association of Exposure to Gas Cooking With Bayley Mental Development Score
Gas Cooking
No.
Score
Mean (SD)
Nod
Yes
1062
825
100.7 (15.4)
99.0 (14.3)
Nod
Yes
329
424
100.9 (15.8)
99.7 (14.8)
Nod
Yes
733
401
100.6 (15.2)
98.3 (13.9)
Unadjusteda
Score (95% CI)
Adjusted for
Socioeconomic Statusb
Score (95% CI)
Overall
0
0
⫺2.3 (⫺3.9 to ⫺0.8)
⫺2.3 (⫺3.8 to ⫺0.8)
Child age at test <14 months
0
0
⫺1.2 (⫺3.6 to 1.1)
⫺1.4 (⫺3.7 to 1.0)
Child age at test >14 months
0
0
⫺3.3 (⫺5.3 to ⫺1.3)
⫺3.1 (⫺5.1 to ⫺1.2)
Fully Adjusted
Modelc
Score (95% CI)
0
⫺2.5 (⫺4.0 to ⫺0.9)
0
⫺1.6 (⫺4.0 to 0.7)
0
⫺3.1 (⫺5.1 to ⫺1.1)
a
Model including sex and region.
Model additionally adjusted for maternal social class, and maternal education.
c
Model additionally adjusted for maternal country of birth, type of house, and gestational age.
d
Reference category.
b
adjusted only for sex and region (⫺2.3 points 关95% confidence
interval (CI)⫽ ⫺3.9 to ⫺0.8兴), and in the model adjusted for
sex, region, maternal social class, and education (⫺2.3 points
关⫺3.8 to ⫺0.8兴) (Table 2). Final adjustment for maternal
country of birth, gestational age, and type of house resulted in
a decrease of ⫺2.5 points (95% CI ⫽ ⫺4.0 to ⫺0.9). The
decrease in the mental score was greater in children tested
after 14 months of age (⫺3.1 points 关⫺5.1 to ⫺1.1兴) than in
children tested at younger ages (⫺1.6 points 关⫺4.0 to 0.7兴;
test for interaction P ⫽ 0.07). Results did not change when
mothers who changed gas cooker status between the third
trimester questionnaire and the 14-month follow-up were excluded, when preterm births were included, or in the completecase analysis (eTable 4, http://links.lww.com/EDE/A523). Gas
cooking was not related to the Bayley psychomotor score
(eTable 4, http://links.lww.com/EDE/A523).
Use of butane/propane gas cookers was related to a
greater reduction in the mental score at test age ⱖ14 months
(⫺6.2 points 关⫺10.3 to ⫺2.2兴) but not overall (Table 3).
Infrequent use of an extractor fan had a small negative effect
on the mental score, in houses both with and without gas
cookers. Reductions in the mental score were greatest in houses
with gas cookers and infrequent use of the extract fan (both test
ages, and overall: ⫺3.7 points 关⫺5.9 to ⫺1.4兴). There were no
clear differences by reported ventilation of the house.
When analyses were stratified by covariates (Table 4),
we observed that the negative effect of gas cooking was fairly
homogeneous in most subcategories and that there was little
evidence for interactions between these variables and the gas
cooking effect (test for interaction P ⬎ 0.1). The strongest
reductions in the mental development score related to gas
cooking were found in the highest and lowest social class
strata, in mothers with medium educational level, in mothers
from non-Spanish origin, in older houses, in urban areas and
areas with higher outdoor NO2 concentrations, and in non6 | www.epidem.com
smoking households. The gas-cooking effect also appeared
somewhat stronger in mother– child pairs with lower intake of
protective nutrients as indicated by shorter breast-feeding,
lower fish consumption, and lower consumption of fruits and
vegetables. Findings were largely similar when children were
stratified by test age ⬍14 months and ⱖ14 months (eTable 5,
http://links.lww.com/EDE/A523). In the subgroup from the
Sabadell region, the gas cooking association was somewhat
stronger in children with the Ile/Val and Val/Val genotypes
(⫺6.5 points 关⫺11.2 to ⫺1.8兴) compared with those who
had the Ile/Ile genotype (⫺3.2 points 关⫺7.8 to 1.5兴). There
was little evidence of a gene– environment interaction
overall (P ⫽ 0.32), although the interaction effect was
stronger (P ⫽ 0.06) in the group of children with test age
ⱖ14 months (eTable 5).
DISCUSSION
The presence of a gas cooker at home during pregnancy
was associated with slower mental development of young
children—particularly those tested after the age of 14 months.
The associations were relatively consistent across social and
educational classes. Given the consistency of exposure over
time within families, it is not possible to determine how
timing of exposure (prenatal versus postnatal) might affect
the association.
These findings support those of a recent study in
Menorca, Spain,21 that found adverse cognitive functioning
and higher risk of inattention symptoms at age 4 years in
relation to early-life exposure to gas appliances and indoor
NO2. The Menorca study found that measured indoor 48-hour
NO2 concentrations were closely correlated with the use of
gas appliances; the study observed similar associations with
neurobehavioral outcomes with both exposure measures. The
replication of an association of gas cooking with neurodevelopment in 2 cohorts of different age groups, using different
© 2011 Lippincott Williams & Wilkins
Epidemiology • Volume 23, Number 1, January 2012
Gas Cooking and Neurodevelopment
TABLE 3. Association of Type of Gas Used, Use of Extractor Fan, and Ventilation of the House With Bayley Mental
Development Scorea
Child Age at Test
<14 Months
Overall
Type of gas used
No gas cookerb
Natural gas
Butane/propane gas
Use of extractor fanc
No gas cooker
Always use extract fanb
Sometimes/never use extract fan
Gas cooker
Always use extract fan
Sometimes/never use extract fan
Ventilation of housec
No gas cooker
Ventilate the house ⬎2 hour per
Ventilate the house ⱕ2 hour per
Gas cooker
Ventilate the house ⬎2 hour per
Ventilate the house ⱕ2 hour per
a
Child Age at Test
>14 Months
No.
Score
(95% CI)
No.
Score
(95% CI)
No.
Score
(95% CI)
1062
583
242
0
⫺2.8
⫺1.6
(⫺4.5 to ⫺1.1)
(⫺3.9 to 0.6)
329
237
187
0
⫺2.7
⫺0.4
(⫺5.4 to 0.1)
(⫺3.3 to 2.6)
733
346
55
0
⫺2.5
⫺6.2
(⫺4.6 to ⫺0.4)
(⫺10.3 to ⫺2.2)
817
227
0
⫺1.0
(⫺3.2 to 1.2)
263
62
0
⫺0.5
(⫺4.7 to 3.8)
554
165
0
⫺1.4
(⫺3.9 to 1.2)
510
258
⫺2.2
⫺3.7
(⫺4.0 to ⫺0.4)
(⫺5.9 to ⫺1.4)
262
136
⫺1.6
⫺2.8
(⫺4.4 to 1.3)
(⫺6.2 to 0.6)
248
122
⫺2.5
⫺4.7
(⫺4.8 to ⫺0.1)
(⫺7.6 to ⫺1.7)
dayb
day
600
437
0
⫺1.0
(⫺2.8 to 0.9)
203
118
0
⫺1.9
(⫺5.4 to 1.7)
397
319
0
⫺0.9
(⫺3.0 to 1.2)
day
day
563
258
⫺2.7
⫺3.0
(⫺4.9 to ⫺0.5)
(⫺4.9 to ⫺1.2)
321
100
⫺1.3
⫺2.7
(⫺5.0 to 2.5)
(⫺5.4 to 0.1)
242
158
⫺3.6
⫺3.6
(⫺6.3 to ⫺0.8)
(⫺6.0 to ⫺1.1)
Model includes sex, region, maternal social class, maternal education, maternal country of birth, type of house, and gestational age.
Reference category.
Excluding persons with missing extractor fan or ventilation data.
b
c
age-appropriate neurodevelopment assessments and different
exposure assessment methods, strengthens the evidence for a
causal association, although similar confounding structures
cannot be excluded as explanation.
A limitation of this study is that assessment of exposure
to gas cookers was based on only one question in the
interviews. We assume that women are able to report the type
of cooker without much error, and in this prospective study,
there is little concern for recall bias. We did not, however,
measure levels of NO2, fine and ultrafine particles, or other
gas-cooking-related pollutants, and we had no information
about factors that can influence exposure, such as the time
spent cooking or the location of the kitchen in relation to
other living spaces. We did find somewhat stronger associations with less frequent use of extractor fans and butane/
propane cookers, which are also predictors of higher indoor
NO2 concentration.8,29 Further, there is little doubt that gas
cooking is a main predictor of indoor NO2 levels, together
with outdoor NO2 and smoking. Studies, including our own
validation studies, have reported concentrations of NO2 1.5to 2-fold higher in living rooms of houses with gas cookers.4,5,7,8,29 However, it is possible that other unmeasured
indoor air pollutants are responsible for our findings. Ultrafine particles, volatile organic compounds, and carbon monoxide are also associated with gas cookers,1,5,10,34,35 and
particulate matter and polycyclic aromatic hydrocarbons have
© 2011 Lippincott Williams & Wilkins
been related to the cooking of food, irrespective of the type of
cooker.6,9,34,36 Better characterization of gas-cooking-related
exposures, preferably through the measurement of associated
pollutants, will be important in future studies.
We assessed the potential for confounding for a wide
range of data on socioeconomic factors, diet and life-style
habits, and exposure to environmental pollutants. Still, we
cannot exclude the possibility that confounding by unmeasured risk factors (eg, maternal IQ, child’s maternal attachment, and home environment indicators) produced the association between gas cooking and neurodevelopment. Gas
cooking was related to social class, education, maternal
country of birth, and other variables such as maternal cigarette smoking. Variables related to housing conditions, such
as the age of the house, were also strongly associated with gas
cooking, but not with neurodevelopment. Adjustment for
these variables produced little change in the regression coefficients. Moreover, the negative effect of gas cooking did not
clearly differ among social variables, making it less likely
that social-class confounding was responsible for the findings. Stratified analyses did tend to show somewhat stronger
associations in older houses, in houses with a higher concentration of outdoor NO2, and in urban areas. Such findings may
indicate a somewhat higher vulnerability of children in the
presence of other pollution exposures, or when living in
adverse housing conditions.
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Epidemiology • Volume 23, Number 1, January 2012
Vrijheid et al
TABLE 4. Association of Exposure to Gas Cooking With
Mental Development Score, Stratified by Covariates
No.
Overall
1887
Maternal social class
I and II
420
III
519
IV and V
948
Maternal education
Primary or secondary
419
High school
785
University
679
Maternal country of origin
Spain
1739
Other
145
Maternal smoking
No
1309
Yes
573
Smoking in house
No
1280
Yes
599
Age of the house (years)
⬍15
945
ⱖ15
887
Urban/rural area
Urban
1527
Semirural/rural
359
Outdoor NO2 concentration (g/m3)
Low ⬍29.1
1017
High ⱖ29.1
816
Breast-feeding (months)
⬍6
1014
ⱖ6
830
Maternal fish consumption (g/day)
⬍69.6
1034
ⱖ69.6
821
Consumption of fruits and vegetables (g/day)
⬍540.4
1042
ⱖ540.4
845
GSTP1 genotypeb
Ile/Ile
150
Ile/Val and Val/Val
172
Score (95% CI)a
⫺2.5 (⫺4.0 to ⫺0.9)
⫺3.5 (⫺6.6 to ⫺0.3)
⫺0.6 (⫺3.6 to 2.4)
⫺3.4 (⫺5.5 to ⫺1.3)
⫺1.6 (⫺4.6 to 1.5)
⫺3.4 (⫺5.7 to ⫺1.1)
⫺1.7 (⫺4.4 to 1.0)
⫺2.1 (⫺3.7 to ⫺0.6)
⫺7.3 (⫺12.9 to ⫺1.7)
⫺2.4 (⫺4.2 to ⫺0.5)
⫺2.5 (⫺5.1 to 0.2)
⫺2.5 (⫺4.4 to ⫺0.6)
⫺1.9 (⫺4.3 to 0.6)
⫺1.3 (⫺3.4 to 0.9)
⫺3.8 (⫺6.0 to ⫺1.6)
⫺2.8 (⫺4.4 to ⫺1.2)
⫺0.9 (⫺4.9 to 3.2)
⫺1.9 (⫺4.1 to 0.3)
⫺2.9 (⫺5.1 to ⫺0.8)
⫺3.5 (⫺5.6 to ⫺1.5)
⫺1.4 (⫺3.7 to 0.9)
⫺3.4 (⫺5.4 to ⫺1.4)
⫺0.9 (⫺3.2 to 1.4)
⫺2.8 (⫺4.8 to ⫺0.8)
⫺2.1 (⫺4.4 to 0.3)
⫺3.2 (⫺7.8 to 1.5)
⫺6.5 (⫺11.2 to ⫺1.8)
a
Model includes sex, region, maternal social class, maternal education, maternal
country of birth, type of house, and gestational age.
b
Sabadell only.
Our study shows a stronger effect of gas-cooking exposure on the mental development of children tested after the
age of 14 months, compared with those tested at younger age.
It is well recognized that these tests can be more variable and
less sensitive in younger children.37 Indeed, studies of the
neurodevelopmental effects of other pollutants have also
observed effects on the Bayley mental development index at
older, but not younger, test ages.14,38 This may be due to
difficulties in testing very young children or due to the fact
8 | www.epidem.com
that effects of pollutants may become apparent only with
maturation of the brain over time. Continued follow-up will
be needed to evaluate possible effects of indoor air pollution
at older ages.
There is increasing experimental evidence that air pollution can cause chronic neuroinflammation and damage the
central nervous system.12 The main mechanisms proposed for
effects of air pollution on the central nervous system are
through systemic effects or through peripheral damage. Inflammatory response of the lung to air pollution exposure
may translate to a wider systemic effect, with oxidative stress
damage in other organs, including the brain.11,12,39,40 Ultrafine particles and compounds absorbed by them (eg, polycyclic aromatic hydrocarbons and metals) may traverse the
blood– brain barrier and cause neuroinflammation, lipid peroxidation, and other damage directly in the brain.12 The exact
mechanisms by which damage is caused are under discussion.
Little is known about direct neurotoxic effects of NO2, but
speculations include a possible mechanism through the peroxidation of brain lipids or through interference with dopamine biosynthesis.21
GSTP1 is included in the super family of glutathione
S-transferase enzymes involved in the phase-II detoxification
of xenobiotic substances, and that protect against the toxic
effects of reactive oxygen and related oxidative stress.41
GSTP1 is mainly expressed in adult lung, placenta, breast,
and urinary bladder, and it is the most strongly expressed
GST isoenzyme in almost all embryonic and fetal tissues,
including the brain,41 making it, of particular, a priori interest. The GSTP1 Ile105Val substitution is located near the
substrate-binding site, resulting in a less active enzyme.42
Other studies have reported higher risks of childhood
asthma and allergic disease associated with traffic-related
air pollution in subjects with this particular polymorphism.43,44 In the Menorca study,21 greater neurodevelopmental effects of NO2- and gas-appliances exposure were
found in the Ile/Val and Val/Val genotypes; we find a
similar result in a small subcohort of our new study,
although we did not have statistical power to draw strong
conclusions. Taken together, the 2 studies suggest that an
oxidative-stress mechanism modified by detoxification
genes may be involved in the neurodevelopmental toxicity
of gas-cooking-related exposures.
The effect of gas cooking on mental development
tended to be somewhat stronger in mothers who consumed
less fish and fewer fruits and vegetables and who breast-fed
for a shorter duration, lending some support to the oxidativestress mechanism. Fruits and vegetables are a rich source of
antioxidant micronutrients,23,45 and fish and breast milk have
high contents of long-chain polyunsaturated fatty acids and
other nutrients that may reduce inflammation and oxidative
stress.46 It should be noted, however, that these dietary
factors were related to social class (data not shown), and that,
© 2011 Lippincott Williams & Wilkins
Epidemiology • Volume 23, Number 1, January 2012
although we adjusted for socioeconomic status indicators, it
is hard to disentangle protective effects of antioxidant intakes
from those of other social-class-related factors.
In conclusion, this study suggests a small adverse effect
of indoor air pollution from gas cookers on mental development. We cannot exclude unmeasured confounding as an
explanation. The potential public health implications of these
findings, if true, are substantial because of the frequent use of
gas cookers and because neurodevelopmental disorders and
disabilities impose a social and economic burden. Future
studies should, wherever possible, use designs that more
accurately assess exposure to indoor air pollutants.
Gas Cooking and Neurodevelopment
17.
18.
19.
20.
21.
ACKNOWLEDGMENTS
We thank all the cohort participants for their collaboration. A full roster of the INMA Project Investigators can be
found at http://www.proyectoinma.org/presentacion-inma/
listado-investigadores/en_listadoinvestigadores.html.
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