Prenatal fine particulate exposure and early childhood asthma: Effect of maternal stress and fetal sex

doi:10.1016/j.jaci.2017.07.017

Journal of Allergy and Clinical Immunology

Volume 141, Issue 5, May 2018, Pages 1880-1886

https://doi.org/10.1016/j.jaci.2017.07.017 Get rights and content

Background

The impact of prenatal ambient air pollution on child asthma may be modified by maternal stress, child sex, and exposure dose and timing.

Objective

We prospectively examined associations between coexposure to prenatal particulate matter with an aerodynamic diameter of less than 2.5 microns (PM_2.5) and maternal stress and childhood asthma (n = 736).

Methods

Daily PM_2.5 exposure during pregnancy was estimated using a validated satellite-based spatiotemporally resolved prediction model. Prenatal maternal negative life events (NLEs) were dichotomized around the median (high: NLE ≥ 3; low: NLE < 3). We used Bayesian distributed lag interaction models to identify sensitive windows for prenatal PM_2.5 exposure on children's asthma by age 6 years, and determine effect modification by maternal stress and child sex.

Results

Bayesian distributed lag interaction models identified a critical window of exposure (19-23 weeks' gestation, cumulative odds ratio, 1.15; 95% CI, 1.03-1.26; per interquartile range [1.7 μg/m³] increase in prenatal PM_2.5 level) during which children concomitantly exposed to prenatal PM_2.5 and maternal stress had increased risk of asthma. No significant association was seen in children born to women reporting low prenatal stress. When examining modifying effects of prenatal stress and fetal sex, we found that boys born to mothers with higher prenatal stress were most vulnerable (19-21 weeks' gestation; cumulative odds ratio, 1.28; 95% CI, 1.15-1.41; per interquartile range increase in PM_2.5).

Conclusions

Prenatal PM_2.5 exposure during sensitive windows is associated with increased risk of child asthma, especially in boys concurrently exposed to elevated maternal stress.

Section snippets

Study participants

Subjects were from the Asthma Coalition on Community, Environment and Social Stress project, a pregnancy cohort originally designed to examine the effects of both chemical and nonchemical exposures on urban childhood asthma risk.¹⁸ Briefly, English- or Spanish-speaking women receiving prenatal care at 2 Boston hospitals and affiliated community health centers were recruited at 28.4 ± 7.9 weeks' gestation between August 2002 and July 2009. Of those approached and deemed eligible, 989 (78.1%)

Results

Mothers were largely ethnic minorities (black 30%, Hispanic 54%) with 12 or less years of education (66%) (Table I). Median maternal age at enrollment was 26 years (interquartile range [IQR], 22-31). Most mothers were nonsmokers (86%) and nonobese (72%). There were 110 asthma cases (15%). Boys were more likely than girls to be diagnosed with asthma (18 vs 12%; χ² test P = .02). Children born to mothers with high prenatal maternal stress (NLE ≥ 3 [n = 308] vs NLE < 3 [n = 428]) were more likely

Discussion

These analyses combine highly temporally resolved ambient PM_2.5 exposure estimates with advanced statistical modeling to determine susceptible windows of exposure to asthma and identify higher-risk subgroups. This is the first study to prospectively demonstrate synergistic effects of prenatal maternal stress and PM_2.5 exposure on childhood asthma risk. Children born to mothers reporting elevated stress in pregnancy and with higher PM_2.5 exposures between 19 and 23 weeks' gestation were

References (39)

W.A. Jedrychowski et al.
Long term effects of prenatal and postnatal airborne PAH exposures on ventilatory lung function of non-asthmatic preadolescent children. Prospective birth cohort study in Krakow
Sci Total Environ
(2015)
I. Copland et al.
Lung development and fetal lung growth
Paediatr Respir Rev
(2004)
Y. Gidron et al.
The relation between psychological factors and DNA-damage: a critical review
Biol Psychol
(2006)
D.M. Stieb et al.
Ambient air pollution, birth weight and preterm birth: a systematic review and meta-analysis
Environ Res
(2012)
S. Gupta et al.
Quantitative computed tomography-derived clusters: redefining airway remodeling in asthmatic patients
J Allergy Clin Immunol
(2014)
A. Hislop
Developmental biology of the pulmonary circulation
Paediatr Respir Rev
(2005)
J. Liu et al.
Sex-specific perinatal nicotine-induced asthma in rat offspring
Am J Respir Cell Mol Biol
(2013)
I. Kloog et al.
A new hybrid spatio-temporal model for estimating daily multi-year PM2.5 concentrations across northeastern USA using high resolution aerosol optical depth data
Atmos Environ
(2014)
R.J. Wright et al.
Programming of respiratory health in childhood: influence of outdoor air pollution
Curr Opin Pediatr
(2013)
P. Latzin et al.
Air pollution during pregnancy and lung function in newborns: a birth cohort study
Eur Respir J
(2009)

W.J. Gauderman et al.

Association of improved air quality with lung development in children

N Engl J Med

(2015)

Y.H. Mathilda Chiu et al.

Prenatal and postnatal maternal stress and wheeze in urban children: effect of maternal sensitization

Am J Respir Crit Care Med

(2012)

A. Lee et al.

Prenatal and postnatal stress and asthma in children: temporal- and sex-specific associations

J Allergy Clin Immunol

(2016)

E. Chen et al.

Chronic traffic-related air pollution and stress interact to predict biologic and clinical outcomes in asthma

Environ Health Perspect

(2008)

T. Islam et al.

Parental stress increases the detrimental effect of traffic exposure on children's lung function

Am J Respir Crit Care Med

(2011)

H.L. Hsu et al.

Prenatal particulate air pollution and asthma onset in urban children: identifying sensitive windows and sex differences

Am J Respir Crit Care Med

(2015)

A. Jorgensen

Oxidatively generated DNA/RNA damage in psychological stress states

Danish Med J

(2013)

J.S. Torday et al.

The sex difference in fetal lung surfactant production

Exp Lung Res

(1987)

N. Ishak et al.

Does lung development differ in male and female fetuses?

Exp Lung Res

(2014)

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: The Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project has been funded by the National Institutes of Health (NIH; grant nos. R01 ES010932, U01 HL072494, and R01 HL080674 to R.J.W., principal investigator), and phenotyping and biostatistical support was funded by NIH grant numbers P30 ES023515, P30 ES000002, and T32 ES007142. During the preparation of this manuscript, A.L. was supported by NIH grant number K23 HL135349 and M.J.R. was supported by NIH grant number T32 HD049311-09.

: Disclosure of potential conflict of interest: A. Lee, S. Bose, J. Schwartz, B. A. Coull, and R. O. Wright received grants from the National Institutes of Health for this work. The rest of the authors declare that they have no relevant conflicts of interest.

View full text

Epidemiology and health care deliveryPrenatal fine particulate exposure and early childhood asthma: Effect of maternal stress and fetal sex

Background

Objective

Methods

Results

Conclusions

Section snippets

Study participants

Results

Discussion

Sci Total Environ

Paediatr Respir Rev

Biol Psychol

Environ Res

J Allergy Clin Immunol

Paediatr Respir Rev

Am J Respir Cell Mol Biol

Atmos Environ

Programming of respiratory health in childhood: influence of outdoor air pollution

Curr Opin Pediatr

Air pollution during pregnancy and lung function in newborns: a birth cohort study

Eur Respir J

Association of improved air quality with lung development in children

N Engl J Med

Prenatal and postnatal maternal stress and wheeze in urban children: effect of maternal sensitization

Am J Respir Crit Care Med

Prenatal and postnatal stress and asthma in children: temporal- and sex-specific associations

J Allergy Clin Immunol

Chronic traffic-related air pollution and stress interact to predict biologic and clinical outcomes in asthma

Environ Health Perspect

Parental stress increases the detrimental effect of traffic exposure on children's lung function

Am J Respir Crit Care Med

Prenatal particulate air pollution and asthma onset in urban children: identifying sensitive windows and sex differences

Am J Respir Crit Care Med

Oxidatively generated DNA/RNA damage in psychological stress states

Danish Med J

The sex difference in fetal lung surfactant production

Exp Lung Res

Does lung development differ in male and female fetuses?

Exp Lung Res

Epidemiology and health care delivery
Prenatal fine particulate exposure and early childhood asthma: Effect of maternal stress and fetal sex