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The association between passive and active tobacco smoke
exposure and child weight status among Spanish children
Oliver Robinson1,2,3, David Martínez1,2,3, Juan J Aurrekoetxea4,5,6, Marisa Estarlich3,7, Ana
Fernández Somoano3,8, Carmen Íñiguez7,3, Loreto Santa-Marina4,5,6, Adonina Tardón3,8, Maties
Torrent9, Jordi Sunyer1,2,3 Damaskini Valvi1,2,3,10 and Martine Vrijheid*1,2,3
1. ISGlobal, Centre for Research in Environmental Epidemiology (CREAL)2. Universitat Pompeu Fabra (UPF)3. CIBER Epidemiología y Salud Pública (CIBERESP)4. Public Health Department, Basque Government, Spain5. University of the Basque Country (UPV/EHU), Spain;6. Health Research Institute (BIODONOSTIA), Spain7. Epidemiology and Environmental Health Joint Research Unit, FISABIO–Universitat
Jaume I–Universitat de València, Spain8. Department of Medicine, University of Oviedo, Spain9. Ib-salut, Area de Salut de Menorca, Spain10. Department of Environmental Health, Harvard T.H. Chan School of Public Health,
United States
Key words: Passive smoking, second hand smoke, overweight, obesity, cotinine
RUNNING TITLE: Passive tobacco smoke exposure and child BMI
*Corresponding author: [email protected]
Parc Recerca Biomèdica de Barcelona, Doctor Aiguader, 88,
08003 Barcelona, Spain
Word count: 3,599
The authors have no potential or actual conflicts of interests to disclose, financial or otherwise.
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FUNDING:
This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), Spanish Ministry of Health (FIS-97/1102, FIS-07/0252, FIS-PS09/00362, 97/0588, 00/0021-2, PI061756, PS0901958, PI14/00677 incl.FEDER funds, FIS-PS09/00090, PI041436, FIS-PI042018, FIS-PI06/0867, PI081151 incl. FEDER funds, FIS-PI09/02311 and FIS-PI13/02187, and FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/0178, 11/02591, 11/02038, PI12/01890 incl. FEDER funds, 13/1944, 13/2032, FIS-PI13/02429, 14/0891, 14/1687 and CP13/00054 incl. FEDER funds), Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822), the Conselleria de Sanitat Generalitat Valenciana, Department of Health of the Basque Government (2005111093, 2009111069 and 2013111089), the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), Fundació La Caixa (97/009-00 and 00/077-00), Beca de la IV convocatoria de Ayudas a la Investigación en Enfermedades Neurodegenerativas de La Caixa, Fundació La marató de TV3 (090430), Obra Social Cajastur/Fundación Liberbank, Universidad de Oviedo, the EU Commission (QLK4-1999-01422, QLK4-CT-2000-00263, QLK4-2002-00603, CONTAMED FP7-ENV-212502, FP7-ENV-2011 cod 282957, HEALTH.2010.2.4.5-1, 261357, 308333, 603794), Agence Nationale de Securite Sanitaire de l'Alimentation de l'Environnement et du Travail (1262C0010), Consejería de Salud de la Junta de Andalucía (grant number 183/07) and Annual agreements with municipalities in the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain).
What is already known about this subject?
-The epidemiological literature consistently shows an association with maternal active smoking and child risk of overweight / obesity.
-The majority of animal studies have shown that rats exposed to nicotine during perinatal development gained more fat mass and body weight than controls
-Only a handful of studies has assessed the effects of passive smoking, either prenatally or by the child postnatally
What does your study add?
-Our study directly addresses both passive smoke exposure by the mother prenatally and in the early life of the child.
-Our study adds corroboration of tobacco smoke exposure with biomarker measurements at both time points and additional detailed assessments of a wide range of socio-demographic, dietary and physical activity covariates.
-We follow children up to the age of 14 years in a subcohort analysis, the oldest yet in studies of passive smoking.
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AbstractObjective: To assess the impact of passive and active tobacco smoke exposure, both pre- and postnatally, on child body mass index (BMI) and overweight.
Methods: Pregnant women were enrolled into the Spanish INMA prospective birth cohort during 1997-2008. Tobacco smoke exposure was assessed by questionnaire and corroborated by pre- and postnatal cotinine measurements. Children were followed up until 4 years in newer subcohorts (N=1866) and until 14 years in one older subcohort (N=427). Child age and sex specific BMI z-scores were calculated and generalized estimating equations were used to model their relationship with repeated measures of tobacco smoke exposure.
Results: We observed associations between prenatal passive exposure to tobacco smoke (adjusted β= 0.15, 95% C.I.: 0.05, 0.25) and active maternal smoking (adjusted β= 0.20, 95% C.I.: 0.08, 0.33) and child zBMI up to 4 years. Stronger associations were observed in the older subcohort between both prenatal and child passive smoke exposure and zBMI up to 14 years.
Conclusions: We have provided evidence for an effect of both passive and maternal active smoking on child postnatal growth. Although residual confounding cannot be completely ruled out, associations were robust to adjustment for a range of lifestyle factors.
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IntroductionThe prevalence of childhood obesity has increased worldwide during the past few decades (1),
and while it is primarily caused by a greater intake of energy than is expended (2), it is
hypothesized that environmental chemical exposures, particularly in utero, may influence
metabolic programming and increase an individual’s susceptibility to obesity (3). Maternal
active smoking during pregnancy is a well documented example of a chemical “obesogen” and
has been associated with childhood obesity in several studies with meta-analyses estimating
odds ratios of around 1.5 for this association (4, 5). Furthermore the majority of animal studies
have shown that rats exposed to nicotine during perinatal development gained more fat mass
and body weight than controls (6). Although unmeasured residual confounding may contribute
to the association observed in human studies, the consistency of the epidemiological evidence
taken together with the toxicological data suggest a causal relationship (6).
Less is known about the association with passive or second hand exposure to tobacco smoke
both by the mother during pregnancy and directly by the child during early life. Only a few
studies have assessed the association between direct measures, through questionnaire or
biomarker, of maternal prenatal passive smoke exposure and child weight status, with
inconsistent results (7, 8, 9). More studies have assessed the effect of partner smoking during
pregnancy, with the majority finding a positive association with child body mass index (BMI)
(9, 10, 11, 12, 13). However there is disagreement regarding whether these effects reflect
residual confounding by familial factors, a biological causal effect due to passive smoke
exposure, or a mixture of both. A handful of studies have investigated the effects of postnatal
child passive smoke exposure and child BMI (9, 12, 14, 15, 16). While the majority of these
studies reported an association with parental reported levels of child exposure, no previous
study has employed biomarker measurements in the child to strengthen the exposure
classification.
In this study of mother-child pairs in the Spanish INMA ( Environment and Childhood)
population-based birth cohort, we present an analysis of the effect of maternal active and
passive smoke exposure during pregnancy and child passive smoke exposure on child weight
status. In a substantial number of mother-child pairs, we have employed both questionnaire and
biomarker based indicators of exposure along with extensive information on lifestyle and
demographic factors, to investigate the effects on child early growth pattern and repeated child
BMI measures up to 4 years. Furthermore in a analysis of an older INMA subcohort, we have
tracked the effect on BMI of children right up to 14 years of age.
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Methods
SubjectsThe INMA birth cohort was established between 2003 and 2008 in the four "new" regional
subcohorts of Asturias, Gipuzkoa, Sabadell and Valencia, and between 1997 and 1998 in the
older Menorca subcohort (17). A total of 3,174 eligible women were recruited during their
routine antenatal examination at the first trimester of pregnancy. To be included women had to
be at least 16 years old, intend to deliver in the reference hospital, have a singleton pregnancy
with no assisted conception, and have no problems with communication. The study was
conducted with the approval of the hospital and institutional ethics committees, and written
informed consent was obtained from all women.
Exposure and covariate information
Questionnaires were administered by trained interviewers twice during pregnancy (at around 12
and 32 weeks of pregnancy) and at child ages of around 1 and 4 years. Information on physical
activity was used to compute overall metabolic equivalent of tasks (METs) levels (19). Maternal
diet was assessed through a validated food frequency questionnaire in the new sub cohorts,
repeated twice during pregnancy (20). Child diet was assessed at 4 years of age through a
similar questionnaire. Maternal pre-pregnancy BMI was calculated from reported pre-pregnancy
weight and measured height at the first visit.
Tobacco smoke exposure categories were constructed from participant responses to a detailed
smoking questionnaire (21) (22) repeated twice during pregnancy and the 1 and 4 year
postnatal follow-up points. In the prenatal period the categories were: 1. "Non smoker" (non-
smoker at beginning of and during pregnancy with no reported passive exposure to tobacco
smoke); 2. "Passive smoker" (Non-smoker at beginning of and during pregnancy with reported
passive exposure to tobacco smoke at home, work or other regularly visited place); 3. "Partial
smoker" (Smoker at beginning of pregnancy or at 12 weeks, who had reported stopping
smoking by the 32 week interview); 4. "Active smoker" (reported being a smoker at the 32
week interview). The postnatal exposure variables were constructed using the current smoking
statuses of the parents at the family home as a proxy of child passive exposure to tobacco
smoke: 1. No parent of the child smokes at home; 2. One of the parents of the child smokes at
home; 3. Both parents of the child smoke at home. These exposure categories were compared
with cotinine measurements made in urine samples collected from the mothers at the 32 week
visit and from the children at the 4 year follow-up in the new sub cohorts. Cotinine, an
established biomarker of recent tobacco exposure, was measured by competitive enzyme
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immunoassay as previously described (21) (22){Aurrekoetxea, 2016 #62}{Aurrekoetxea, 2016
#62}. Values below the limit of detection (LOD, 4 ng/mL) were replaced by 2 ng/mL.
Outcome assessmentChild weight and height were measured at each follow-up visit using standard protocols,
without shoes and in light clothing. We calculated BMI (weight/height2) and used the WHO
reference curves to estimate age- and sex-specific BMI Z-scores (zBMI) (23). Overweight was
defined as a zBMI ≥ the 85th percentile. Children were defined as rapid or normal growers in
the first six months of life using repeat weight measurements extracted from their medical
records, with those children with a difference between birth and 6 month weight Z-scores
greater than 0.67 standard deviations from the mean considered rapid growers (24).
Statistical analysesWe assessed the four new INMA subcohorts together in a pooled analysis and the older
Menorca subcohort in a separate analysis. We assessed the association between tobacco smoke
exposure and child weight status up to 4 years in the pooled analysis and up to 14 years in the
Menorca analysis. In the pooled analysis, to incorporate both repeated measures of child weight
status and postnatal exposure status (assessed at 1 and 4 years)., we used generalised estimating
equations (GEE) with an unstructured correlation matrix and a Gaussian or binomial
distribution specification (for continuous and dichotomous outcomes, respectively). Since in
the Menorca subcohort analysis, we had more repeat measurement points of outcome than
exposure, GEE was used only to model the outcome data (assessed at 4, 6, 11 and 14 years),
with postnatal tobacco smoke exposure assessed at the 4 years time point only. In the pooled
analysis, we assessed rapid growth using logistic regression.
Basic and fully adjusted models were adjusted for child sex and with an indicator variable for
subcohort in the pooled analyses. Additional potential covariates for inclusion in fully adjusted
models were selected from the literature (14). The variables considered in both the pooled and
Menorca subcohort analyses were socio-economic status (paternal occupation class and
education, maternal occupation class and education), maternal country of origin (Spanish,
other), maternal age, maternal BMI, breastfeeding (ever breastfeeding and breastfeeding
duration) and child physical and sedentary activity at 4 years (hours/week spent sleeping,
watching TV and engaging in sedentary activities; total METs expended over week during
commute to school, during sedentary activities, during physical activities in and outside the
school). In the pooled analyses, we additionally examined paternal BMI, maternal physical
activity (average total METs/week), maternal alcohol consumption, and maternal and child diet
(daily averages over pregnancy and at child age 4 years including total calories, total fat, total
proteins, total carbohydrates, total fruit, total vegetables and total sugar consumption). Those
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covariates significantly ( p < 0.05) related in bivariate testing to both exposure (χ2 or ANOVA
tests), and outcome (χ2 or Pearson's correlations) , in addition to maternal and paternal BMI and
education, were then considered for inclusion in the final model. To prevent over-fitting, only
those covariates that modified the exposure coefficient by ≥ 10% following forward stepwise
procedure were retained. 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 (table 1). We created 20 imputations, generating 20 complete datasets that we
analyzed following the standard combination rules for multiple imputations (25). Results using
the complete case dataset are provided for comparison with imputed results in supplementary
tables s6 and s7.
Further analyses included sensitivity analyses where children born prematurely (< 37 weeks
gestational age) and with birth weight below 2500g were excluded. To test the robustness of our
results we also stratified by child sex, maternal BMI and maternal social class. Interactions
between tobacco smoke exposure and stratification variables was assessed by likelihood ratio
tests.. All analyses were conducted with Stata 12.0 statistical software (Stata
Corporation,College Station, TX).
ResultsAfter excluding women who withdrew, were lost to follow-up, or underwent abortions or fetal
deaths, 2644 pregnant women in the new subcohorts and 443 in the Menorca subcohort were
monitored through delivery. Final analyses included 1927 children with exposure and outcome
data up to 4 years in the new subcohorts (72% of those followed to birth) and 427 children
followed until 14 years in the Menorca sub cohort (96% of those followed to birth) . Women
lost to follow-up by the time the child was aged 1.5 years were more likely to be of lower social
class and have smoked at any time during pregnancy (17).
Mothers who were not prenatally exposed to tobacco smoke were on average better educated
and of higher occupational social class, had lower pre-pregnancy BMI, and consumed less total
calories, fat and alcohol and more vegetables and fruits during pregnancy than mothers who
were exposed to tobacco smoke (tables 1 and 2). The children of non-exposed mothers had
higher birth weight, breastfed for longer and tended to sleep for longer, spend less time
watching television, and consume less calories, fat and sugar and more fruit at four years of age
(tables 1 and 2). Maternal and paternal BMI and child birth weight were all positively
associated with zBMI of the child at 4 years (all p < 0.001) (supplementary tables 1 and 2).
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Boys and children who consumed more fruit and total sugar and watched more television at 4
years also had higher zBMI scores at 4 years (tables s2 and s3).
New subcohorts analysisIn the new INMA sub cohorts in Asturias, Gipuzkoa, Sabadell and Valencia, 697 (36%) of
mothers were non-smokers, 571 (30%) were passive smokers, 317 (16%) were "partial
smokers" and 342 (18%) were active smokers throughout pregnancy. At 4 years, 1289 (79%)
children had no parents who smoked at home, 209 (13%) had one parent who smoked at home
and 140 (9%) had two parents who smoked at home. These ordinal categories from
questionnaire data were significantly related to respective urinary cotinine levels in the mother
at 32 weeks of pregnancy (p < 0.001) and in the child at 4 years (p < 0.001) (figure 1, table 1).
In 42% of the households where the mother was an active smoker throughout pregnancy, at
least one parent smoked at home at child age 4 years. In the final model of the pooled analysis,
adjusted for maternal BMI, subcohort and gender following the variable selection procedure,
maternal tobacco smoke exposure status during pregnancy was significantly associated with
child weight status up to 4 years (table 3). Compared to non-smokers, the associations with
child zBMI up to 4 years was as follows: children of passive smokers had on average a higher
zBMI of 0.15 SDs (95% C.I: 0.05, 0.25); for children of partial smokers, zBMI was 0.08 SDs
higher (95% C.I: -0.05, 0.21); and for children of active smokers, zBMI was 0.20 SDs higher
(95% C.I. = 0.08, 0.33). Similar results were observed with child overweight up to four years
(table 3). Only active smoking was significantly associated with rapid weight gain in the first 6
months of life, with an Odds Ratio (OR) of 2.03 (95% C.I: 1.49, 2.76) (table 3). These
associations were similar in the basic models and in additionally-adjusted models that included
further socio-economic and lifestyle indicators as co-variates (table s4). No significant
associations were observed between child postnatal exposure and weight status up to age 4
years: Compared to children who had no parents who smoked, the average zBMI among
children who had one parent that smoked was 0.07 SDs higher (95% C.I: -0.04, 0.18) and for
children that had two parents that smoked it was 0.05 SDs higher (95% C.I: -0.08, 0.19). When
both the prenatal and postnatal exposure variables were included in the same model, the
postnatal estimates were attenuated (table 3).
There was very little difference in estimates when children born prematurely (table s5) or at low
birth weight (table s6) were excluded from the analysis, with the exception of the association
between rapid growth and active maternal smoking during pregnancy which was attenuated
somewhat when low birth weight children were excluded. Repeat of the pooled analysis of
prenatal exposure and child zBMI up to 4 years stratified by key covariates did not provide any
evidence for interaction in effect with gender (p for interaction = 0.65) or social class (p for
interaction = 0.61), although there were slightly stronger effects among boys and larger effects
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associated with maternal active smoking among children of mothers of lower social class (figure
2). There was a significant interaction with maternal BMI (p for interaction = 0.01), with
stronger effects of maternal passive and active smoking on child zBMI observed among
overweight (BMI > 25) mothers (figure 2).
Menorca subcohort analysisIn the Menorca subcohort 174 (41%) of mothers were non-smokers, 96 (22%) were passive
smokers, 83 (19%) were partial smokers and 74 (17%) were active smokers during pregnancy.
At 4 years, 210 (49%) children had no parents who smoked at home, 146 (34%) had one parent
who smoked and 71 (17%) had two parents who smoked at home. In 78% of the households
where the mother was an active smoker throughout pregnancy, at least parent smoked at home
when the child was aged four years. (table 2). The mean zBMI of children at 4 years in the
Menorca subcohort was 0.59 (SD: 1.01), with 15.2% being classified as overweight. At 14
years, the mean zBMI was 0.34 (SD: 1.04), with 15.3 % being classified as overweight.
In the Menorca analysis, the associations between tobacco smoke exposure and child weight
status were stronger (table 4). Compared to non-smokers, the association between prenatal
exposure groups and child zBMI up to 14 years in the fully adjusted model was as follows:
zBMI was 0.17 SDs higher (95% C.I: -0.06, 0.40) among children of passive smokers, 0.34
SDs higher (95% C.I: 0.10, 0.59) among children of partial smokers, and 0.33 SDs higher (95%
C.I. = 0.08, 0.58) among children of active smokers. In contrast to the pooled analysis there
were significant associations with postnatal tobacco smoke exposure of the child. zBMI up to 14
years among children who had one parent that smoked at the 4 year follow-up was 0.27 SDs
higher (95% C.I: (0.08, 0.47) and for children that had two parents that smoked, it was 0.39 SDs
higher (95% C.I: 0.14, 0.65) compared to children that had no parents who smoked. When the
prenatal and postnatal exposure points were included in the same model, effects at each time
point were attenuated (table 4).
DiscussionOur results have indicated that both passive and active (maternal) exposure to tobacco smoke
are associated with child BMI and overweight. We observed effects of maternal active smoking
that were broadly in line with the effect sizes estimated for the meta analyses by Oken et al. (4)
of 14 studies with overweight at 3–33 years of age (OR = 1.50; 95% CI: 1.36, 1.65) and by Ino
et al (5) for obesity (BMI > 95th percentile, OR = 1.64, 95% CI: 1.42, 1.90) based on 16
studies. The present study adds to the consistency of associations observed across a variety of
social, geographic and temporal contexts. Far less information is available on the effect of
exposure to passive smoke by the mother during pregnancy. Oken et al (7) reported no
association with self-reported levels. Braun et al. (8) used multiple serum cotinine
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measurements during pregnancy to assess passive smoke exposure and observed a slightly
higher BMI at three years of age in offspring of exposed mothers. Florath (9) used cord serum
cotinine levels to validate maternal non-, passive and active smoker categories during pregnancy
and observed a trend for increased BMI at 8 years in children of passive smokers (of similar
effect size to the present study) and a greater significant effect among children of active
smokers.
Parental smoking during pregnancy may also reflect child passive smoke exposure postnatally.
We did not observe any significant association with zBMI or overweight up to 4 years with
parental smoking during childhood in our larger pooled analysis. However we saw larger
significant associations both prenatally and postnatally with parental smoking in the Menorca
analysis that analyzed effects on child BMI up to 14 years of age. This difference may partially
reflect the greater proportion of mothers who actively smoked during pregnancy that continued
during the early life of their child in Menorca. Furthermore associations with postnatal passive
smoke exposure may only become apparent at later ages. Many studies have reported stronger
effects of tobacco smoke exposure as children become older (8, 10, 13, 26)(11, 27). Changing
attitudes, following the introduction of anti-smoking legislation, in the newer cohorts may also
have resulted in lower exposure levels of the child within each exposure category. A number of
studies have now also associated parental reported measures of postnatal passive smoke
exposure with child BMI (9, 14, 15, 16) however in the presence of multicolinearity between
the pre- and postnatal exposure periods it is difficult to separate the effects of each period.
Moller et al. (12) took advantage of the large sample size in the Danish birth cohort study to
stratify children by exposure prenatally only, postnatally only or exposed at both periods, with
results indicating that exposure at both periods of child development are important.
Although smoking is well known to be related to socio-demographic factors, in the present
study adjustment for lifestyle indicators did not appreciably alter associations with tobacco
smoke exposure and child BMI, strengthening the inference of causality. The weight of
epidemiological evidence is currently stronger for the effects of maternal active smoking than
for passive smoking. We observed strong effects of prenatal passive smoking in both presented
analyses, which may be considered larger than expected relative to the effects of active
smoking, considering the large relative difference in the magnitude of exposure (as indicated by
the urinary cotinine measurements in each exposure group). While the actual effect size of
prenatal passive smoking may in fact be smaller than estimated here within the presented 95%
confidence interval, we may also not expect a linear dose-response curve since passive low dose
exposure may act through a different mechanism than high dose active exposure. We found that
active smoking, but not passive smoking, was associated with rapid growth in the first six
months of life. Early rapid growth is a risk factor for the later development of childhood obesity
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(28) and can result from impaired fetal growth. We have previously reported within the INMA
study that fetal growth is impaired among actively smoking mothers, which is postulated to
result from placental insufficiency due to vascular damage (29). Alternative mechanisms by
which tobacco smoke exposure may act, even at low dose passive exposure, is through
activation of hormonal systems which influence metabolic programming (30, 31, 32) and/or
through influence of child appetite and circulating leptin levels (33, 34). These results may be
relevant for other environmental pollutants, for which exposure assessment is less certain, that
interact with similar cellular receptors (6).
Since a single urinary cotinine measurement reflects recent tobacco smoke exposure (35), we
primarily used the questionnaire information to classify individuals based on long-term
exposure. While some participants that reported being unexposed had low levels of detectable
cotinine, average cotinine levels in both the mother during pregnancy and in the child were
supportive of the questionnaire-based classification. However, cotinine measurements were not
available in the Menorca subcohort and this information would have allowed us to ascertain if
average exposure levels with passive smoke exposure groupings were different in the older
subcohort. Other limitations include the use of BMI as the outcome measure, which is a blunter
assessment of adiposity than direct measures such as dual-energy X-ray absorptiometry (36).
Furthermore, a larger sample size may have allowed increased stratification to tease apart the
effects of different exposure periods. However, strengths of this study include its prospective
nature and the use of repeated in-depth face to face interviews with mothers allowing the
collection of detailed information on exposure and lifestyle factors. We employed repeated
measures of BMI over early life and in the older Menorca subcohort, tracked BMI up to 14 year
of age, the oldest yet followed in prospective studies of passive smoke exposure and BMI.
In summary, we have demonstrated an association between both active maternal and passive
tobacco smoke exposure and child BMI and overweight. Although residual confounding cannot
be ruled out, this study adds to a growing body of epidemiological and toxicological evidence
suggesting passive smoke exposure may contribute to the pathogenesis of obesogenic child
growth.
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Figures and tables
Figure 1. Cotinine measurements (ng/mL,) at 32 weeks of pregnancy and in the child at 4 years. Circles indicate median levels while error bars show 25th and 75th percentiles.
Figure 2. Effect of maternal prenatal tobacco smoke exposure and child zBMI up to 4 years in the 'new' sub cohorts, stratified by key covariates. Maternal social class: CS I-II-III = professional, managerial or skilled occupations; CS IV-V = unskilled occupations.
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Table 1 . Participant demographic and lifestyle information in the new sub cohorts, by maternal smoking status during pregnancy
Maternal smoking status during pregnancy
Non Smoker697 (36.2)1
Passive Smoker
571 (29.6)
Partial Smoker317 (16.5)
Active smoker342 (17.7) p value
Maternal/Paternal socio-demographics
Maternal education
Primary 110 (26.4)1 95 (22.8) 82 (19.7) 129 (31) <0,001
Secondary 273 (34) 219 (27.3) 145 (18.1) 166 (20.7)
University 312 (44.3) 257 (36.5) 90 (12.8) 46 (6.5)
missing 2 ( 0.1 ) 0 ( 0 ) 0 ( 0 ) 1 ( 0.1 )Maternal Social Class
CSV I+II+III (professional, managerial, skilled) 398 (41.5) 307 (32.1) 140 (14.6) 113 (11.8) <0,001
CS IV+V (unskilled) 298 (30.8) 264 (27.3) 177 (18.3) 229 (23.7)
missing 1 ( 0.1 ) 0 ( 0 ) 0 ( 0 ) 0 ( 0 )Maternal ethnicity
Spain 633 (35.5) 524 (29.4) 296 (16.6) 332 (18.6) 0,016
Other 62 (44.9) 45 (32.6) 21 (15.2) 10 (7.2)missing 2 ( 0.1 ) 2 ( 0.1 ) 0 ( 0 ) 0 ( 0 )
Maternal age
<25 26 (23.4) 27 (24.3) 30 (27) 28 (25.2) <0,001
25-29 184 (30.5) 184 (30.5) 111 (18.4) 125 (20.7)
30-34 318 (37.5) 260 (30.7) 135 (15.9) 134 (15.8)
35+ 168 (46.2) 100 (27.5) 41 (11.3) 55 (15.1)
missing 1 ( 0.1 ) 0 ( 0 ) 0 ( 0 ) 0 ( 0 )Maternal BMI
<18.5 25 (30.5) 17 (20.7) 17 (20.7) 23 (28) 0,027
18.5-25 498 (37.2) 396 (29.6) 226 (16.9) 217 (16.2)
25-30 124 (34.2) 107 (29.5) 60 (16.5) 72 (19.8)
More than 30 50 (34.5) 51 (35.2) 14 (9.7) 30 (20.7)
missing 0 0 0 0Paternal BMI 26.1 ±3.39 25.82 ±3.47 25.82 ±3.18 26.28 ±3.95 0,239
missing 12 (1.7) 14 (2.5) 4 (1.3) 3 (0.9)Maternal urinary cotinine at 32 weeks pregnancy (ng/mL) 8.9 ±59.5 42.8 ±370.9 210.1 ±554.1 2089.5 ±1497.9 <0,001
missing 40 39 33 28
Diet and physical activity of mother during pregnancy
Total Calories (kcals) 1956.69 ±372.4 2029.17 ±471.64 2129.57 ±479.34 2266.67
±518.35 <0,001
missing 10 (1.4) 10 (1.8) 5 (1.6) 6 (1.8)Adjusted total fat (g) 83.45 ±11.17 83.31 ± 11 85.08 ±11.03 85.67 ±10.9) 0,004
missing 10 (1.4) 10 (1.8) 5 (1.6) 6 (1.8)Adjusted proteins (g) 96.16 ±11.67 95.03 ±11.56 94.47 ±11.73 94.33 ±11.75 0,022
missing 10 (1.4) 10 (1.8) 5 (1.6) 6 (1.8)
Adjusted carbohydrates (g) 236.04 ±27.15 237.09 ±28.11 232.85 ±28.38 230.32 ±26.53 0,001
missing 10 (1.4) 10 (1.8) 5 (1.6) 6 (1.8)Adjusted Vegetables (g) 225.64 ±89.64 212.08 205.87 ±96.85 209.05 ±117.43 <0,001
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Maternal smoking status during pregnancy
Non Smoker697 (36.2)1
Passive Smoker
571 (29.6)
Partial Smoker317 (16.5)
Active smoker342 (17.7) p value
±91.95missing 10 (1.4) 10 (1.8) 5 (1.6) 6 (1.8)
Adjusted Fruits (g) 354.47 ±164.43 337.2 ±160.41 310.45 ±160.27 266.63 ±152.43 <0,001
missing 10 (1.4) 10 (1.8) 5 (1.6) 6 (1.8)Alcohol consumption (g) 0.17 ±0.57 0.25 ±0.88 0.33 ±1.03 0.61 ±1.59 <0,001
missing 10 (1.4) 10 (1.8) 5 (1.6) 6 (1.8)Physical activity per day
during pregnancy (METs) 37.35 ±2.95 37.29 ±3.07 37.06 ±3.21 37.44 ±3.1 0,382
missing 14 (2) 13 (2.3) 7 (2.2) 11 (3.2)
Early life factors Mean length of breast
feeding (months) 27.09 ±22.87 26.29 ±22.03 24.88 ±20.87 20.14 ±22.27 <0,001
missing 12 (1.7) 8 (1.4) 6 (1.9) 4 (1.2)
Birthweight (g) 3306.11 ±446.85 3305.76 ±440.2 3285.02 ±468.39 3124.62
±458.03 <0,001
missing 4 (0.6) 1 (0.2) 2 (0.6) 2 (0.6)Diet and physical activity of child at four years
Total Calories (kcals) 1557.57 ±314.84 1575.44 ±362.97 1610.16 ±384.15 1675.18
±348.26 <0,001
missing 115 (16.5) 91 (15.9) 57 (18) 59 (17.3)Total fat (g) 62.46 ±15.66 62.52 ±17.12 64.39 ±17.46 68.25 ±16.96 <0,001
missing 115 (16.5) 91 (15.9) 57 (18) 59 (17.3)Adjusted3 Vegetables (g) 67.58 ±36.63 67.31 ±39.22 60.79 ±37.89 60.34 ±38.16 0,003
missing 115 (16.5) 91 (15.9) 57 (18) 59 (17.3)
Adjusted Fruits (g) 172.28 ±102.32 157.51 ±102.81 147.59 ±83.51 145.89 ±107.18 <0,001
missing 115 (16.5) 91 (15.9) 57 (18) 59 (17.3)Adjusted proteins (g) 67.79 ±6.96 68.21 ±6.76 68.33 ±7.65 67.48 ±6.79 0,382
missing 115 (16.5) 91 (15.9) 57 (18) 59 (17.3)Adjusted carbohydrates (g) 188.41 ±19.7 188.9 ±19.57 187.35 ±20.54 186.25 ±19.03 0,389
missing 115 (16.5) 91 (15.9) 57 (18) 59 (17.3)Sugar (g) 92.38 ±27.27 94.67 ±33.2 96.36 ±34.61 100.62 ±31.91 0,005
missing 115 (6) 91 (4.7) 57 (3) 59 (3.1)Sleep duration (hours/week) 73.37 ±6.27 72.98 ±6.85 71.93 ±7.88 72.47 ±7.37 0,005
missing 90 (12.9) 73 (12.8) 49 (15.5) 53 (15.5)Tv viewing (hours/week) 9.24 ±5.43 9.85 ±5.84 10.52 ±5.76 10.81 ±6.49 0,001
missing 93 (13.3) 73 (12.8) 50 (15.8) 58 (17)Physical activity per day at
school (METs) 24.98 ±12.04 29.46 ±14.31 30.07 ±15.25 28.87 ±14.12 <0,001
missing 253 (36.3) 222 (38.9) 121 (38.2) 118 (34.5)Child BMI and age at clinical examination
Age at 4 years 4.41 ±0.19 4.42 ±0.22 4.41 ±0.19 4.38 ±0.18 0.027
missing 88 (12.6) 67 (11.7) 50 (15.8) 53 (15.5)
BMI at 1 year 17.23 ±1.32 17.39 ±1.49 17.23 ±1.46 17.49 ±1.52 0.177
missing 216 (31) 195 (34.2) 122 (38.5) 123 (36)
zBMI at 1 year 0.41 ±0.9 0.51 ±0.98 0.43 ±0.96 0.59 ±1 0.156
missing 218 (31.3) 196 (34.3) 123 (38.8) 125 (36.5)
BMI at 4 years 16.11 ±1.49 16.35 ±1.64 16.25 ±1.66 16.4 ±1.77 0.126
14
Maternal smoking status during pregnancy
Non Smoker697 (36.2)1
Passive Smoker
571 (29.6)
Partial Smoker317 (16.5)
Active smoker342 (17.7) p value
missing 90 (12.9) 70 (12.3) 50 (15.8) 53 (15.5)
zBMI at 4 years 0.54 ±0.98 0.68 ±1 0.62 ±1.08 0.70 ±1.07 0.174
missing 90 (12.9) 71 (12.4) 50 (15.8) 54 (15.8)Postnatal Parental smoking status
At child age 1 year
No parent smokes at home 646 (42.4) 479 (31.4) 222 (14.6) 177 (11.6) <0,001
One parent smokes at home 15 (9) 54 (32.3) 40 (24) 58 (34.7)
Both parents smoke at home 2 (1.9) 8 (7.7) 23 (22.1) 71 (68.3)
missing 34 ( 1.9 ) 30 ( 1.7 ) 32 ( 1.8 ) 36 ( 2 )At child age 4 year
No parent smokes at home 579 (44.9) 427 (33.1) 173 (13.4) 110 (8.5) <0,001
One parent smokes at home 20 (9.6) 54 (25.8) 49 (23.4) 86 (41.1)
Both parents smoke at home 2 (1.4) 10 (7.1) 43 (30.7) 85 (60.7)
missing 96 ( 5.9 ) 80 ( 4.9 ) 52 ( 3.2 ) 61 ( 3.7 )
1 n (%) for categorical variables.
2 Mean ± SD for continuous variables.
3 These dietary variables adjusted for total calories consumed
15
Table 2 . Participant demographic and lifestyle information in the Menorca sub cohort, by maternal smoking status during pregnancy
Maternal smoking status during pregnancy
Non Smoker174 (41) 1
Passive Smoker96 (22)
Partial smoker83 (19)
Active smoker74 (17)
p value
Maternal/Paternal socio-demographics
Maternal education
Primary 95 (39.4)1 44 (18.3) 56 (23.2) 46 (19.1) 0.141
Secondary 45 (40.9) 31 (28.2) 16 (14.5) 18 (16.4)
University 26 (46.4) 15 (26.8) 8 (14.3) 7 (12.5)
missing 8 6 3 3
Maternal Social Class
CS I+II+III (professional, managerial, skilled)
118 (44.0) 65 (24.3) 47 (17.5) 38 (14.2) 0.024
CS IV+V (manual or non-manual) 17 (27.4) 14 (22.6) 14 (22.6) 17 (27.4)
missing 39 17 22 19
Maternal age
<25 10 (19.6) 8 (15.7) 19 (37.3) 14 (27.5) 0.010
25-29 74 (42.3) 41 (23.4) 32 (18.3) 28 (16)
30-34 65 (46.1) 31 (22) 23 (16.3) 22 (15.6)
35+ 21 (37.5) 16 (28.6) 9 (16.1) 10 (17.9)
missing 4 0 0 0
Maternal ethnicity
Spain 169 (40.9) 91 (22) 82 (19.9) 71 (17.2) 0.335
Other 3 (25) 5 (41.7) 1 (8.3) 3 (25)
Missing 2 (100) 0 (0) 0 (0) 0 (0)
Maternal BMI
<18.5 6 (30) 3 (15) 6 (30) 5 (25) 0.072
18.5-25 125 (40.6) 71 (23.1) 62 (20.1) 50 (16.2)
25-30 28 (45.9) 8 (13.1) 10 (47.6) 15 (24.6)
More than 30 6 (28.6) 10 (47.6) 3 (14.3) 2 (9.5)
missing 9 4 2 2
Early life factors
Breastfeeding
None 22 (31.4) 16 (22.9) 16 (22.9) 16 (22.9) 0.032
<6 months 70 (35.9) 44 (22.6) 45 (23.1) 36 (18.5)
>= 6 months 82 (50.6) 36 (22.2) 22 (13.6) 22 (13.6)
missing 0 0 0 0
Birth weight (g)2 3249.5 ±490.8 3208.4 ±452.7 3270.9 ±474.06 3035.81 ±403.97 0.003
missing 0 0 0 0
Child physical activity at child age 4 years
Sleep duration (hours / week) 73.27 ±4 72.94 ±4.16 73.24 ±4.85 71.92 ±5.04 0.434
missing 1 0 0 0
TV viewing (hours/week) 7.33 ±3.91 7.66 ±4.19 8.1 ±5.08 8.71 ±4.86 0.282
16
Maternal smoking status during pregnancy
Non Smoker174 (41) 1
Passive Smoker96 (22)
Partial smoker83 (19)
Active smoker74 (17)
p value
missing 1 0 0 1
Outside school physical activity (METs)
14.26 ±12.45 16.32 ±12.8 17.71 ±13.6 15.37 ±13.1 0.057
missing 1 0 0 0
Parental smoking status at child age 4 years
No parent smokes at home 161 (76.7) 26 (12.4) 15 (7.1) 8 (3.8) 0.000
One parent smokes at home 13 (8.9) 64 (43.8) 34 (23.3) 35 (24)
Both parents smoke at home 0 (0) 6 (8.5) 34 (47.9) 31 (43.7)
missing 0 0 0 0
Child characteristics at 14 year clinical examination
Age 14.6 ±0.2 14.6 ±0.2 14.6 ±0.2 14.6 ±0.2 0.268
missing 42 24 25 24
Bmi 20.5 ±2.7 21.2 ±3.6 22.1 ±3.9 22.1 ±3.8 0.002
missing 42 24 25 24
zbmi 0.15 ±0.9 0.32 ±1.1 0.59 ±1.2 0.63 ±1.1 0.009
missing 42 24 25 24
17
Table 3: Adjusted models in the pooled analysis of the four 'new' INMA cohorts, showing relationships between tobacco smoke exposure and child weight status measured at 1 and 4 years of age and rapid growth in the first six months of life.
zBMI1 Overweight1 Rapid growth 0-6 month2
N Beta (95% CI) N of cases/controls OR (95% CI)
N of case/
controlsOR (95% CI)
Smoking status of mother during pregnancy
Non smoker 683 0 118/565 1 133/472 1
Passive smoker 553 0.15 (0.05, 0.25) 119/434 1.36 (1.02, 1.80) 110/393 0.99 (0.75, 1.33)
Partial smoker 303 0.08 (-0.05, 0.21) 58/245 1.30 (0.91, 1.84) 77/197 1.34 (0.97, 1.87)
Active smoker 327 0.20 (0.08, 0.33) 83/244 1.78 (1.29, 2.45) 115/190 2.03 (1.49, 2.76)
Postnatal tobacco exposure of the child
No parent smokes 1527 0 282/1245 1
1 parent smokes 204 0.07 (-0.04, 0.18) 62/142 1.14 (0.82, 1.57)Both parents
smoke 135 0.05 (-0.08, 0.19) 34/101 0.99 (0.65, 1.5)
Prenatal and postnatal exposure (mutually adjusted model)
Smoking status of mother during pregnancy
Non smoker 683 0 118/565 1
Passive smoker 553 0.16 (0.06, 0.27) 119/434 1.36 (1.02, 1.81)
Partial smoker 303 0.09 (-0.04, 0.22) 58/245 1.31 (0.92, 1.88)
Active smoker 327 0.20 (0.06, 0.33) 83/244 1.90 (1.33, 2.69)
Postnatal tobacco exposure of the child
No parent smokes 1527 0 282/1245 1
1 parent smokes 204 0.02 (-0.10, 0.14) 62/142 0.93 (0.66, 1.3)Both parents
smoke 135 0.03 (-0.13, 0.18) 34/101 0.74 (0.48, 1.16)
1. Adjusted by subcohort, sex and maternal pre-pregnancy BMI
2. Adjusted by subcohort and gender
18
Table 4. Adjusted models in the Menorca subcohort analysis showing relationships between tobacco smoke exposure and child weight status measured at 4, 6, 11 and 14 years of age
zBMI1 Overweight1
N Beta (95% CI)N of
cases/controls
OR (95% CI)
Smoking status of mother during pregnancyNon smoker 174 0 32/142 1
Passive smoker 96 0.17 (-0.06, 0.40) 25/71 2.09 (1.13, 3.87)
Partial smoker 83 0.34 (0.10, 0.59) 23/60 3.12 (1.71, 5.69)
Active smoker 74 0.33 (0.08, 0.58) 25/49 2.90 (1.58, 5.32)
Postnatal tobacco exposure of the child at 4 years
No parent smokes 210 0 38/172 1
1 parent smokes 146 0.27 (0.08, 0.47) 42/104 2.38 (1.44, 3.94)
Both parents smoke 71 0.39 (0.14, 0.65) 27/44 3.40 (1.92, 6.02)
Prenatal and postnatal exposure (mutually adjusted model)
Smoking status of mother during pregnancy
Non smoker 174 0 32/142 1
Passive smoker 96 0.03 (-0.26, 0.32) 25/71 1.40 (0.65, 3.00)
Partial smoker 83 0.16 (-0.16, 0.48) 23/60 1.82 (0.81, 4.06)
Active smoker 74 0.13 (-0.20, 0.47) 25/49 1.63 (0.71, 3.74)
Tobacco exposure post pregnancy 4 year
No parent smokes 210 0 38/172 1
1 parent smokes 146 0.21 (-0.05, 0.48) 42/104 1.77 (0.90, 3.47)
Both parents smoke 71 0.27 (-0.07, 0.61) 27/44 2.24 (1.00, 4.98)
1 Adjusted by sex and maternal pre-pregnancy BMI
19
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