Background: Air pollution exposure during pregnancy has been associated with impaired fetal growth. However, few studies have measured fetal biometry longitudinally, remaining unclear as to whether there are windows of special vulnerability.

Objective: The aim was to investigate the impact of nitrogen dioxide (NO₂) exposure on fetal and neonatal biometry in the Spanish INMA study.

Methods: Biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were evaluated for up to 2,478 fetuses in each trimester of pregnancy. Size at 12, 20, and 34 weeks of gestation and growth between these points, as well as anthropometry at birth, were assessed by SD scores derived using cohort-specific growth curves. Temporally adjusted land-use regression was used to estimate exposure to NO₂ at home addresses for up to 2,415 fetuses. Associations were investigated by linear regression in each cohort and subsequent meta-analysis.

Results: A 10-μg/m³ increase in average exposure to NO₂ during weeks 0–12 was associated with reduced growth at weeks 0–12 in AC (–2.1%; 95% CI: –3.7, –0.6) and EFW (–1.6%; 95% CI: –3.0, –0.3). The same exposure was inversely associated with reduced growth at weeks 20–34 in BPD (–2.6%; 95% CI: –3.9, –1.2), AC (–1.8%; 95% CI: –3.3, –0.2), and EFW (–2.1%; 95% CI: –3.7, –0.2). A less consistent pattern of association was observed for FL. The negative association of this exposure with BPD and EFW was significantly stronger in smoking versus nonsmoking mothers.

Conclusions: Maternal exposure to NO₂ in early pregnancy was associated with reduced fetal growth based on ultrasound measures of growth during pregnancy and measures of size at birth.

Citation: Iñiguez C, Esplugues A, Sunyer J, Basterrechea M, Fernández-Somoano A, Costa O, Estarlich M, Aguilera I, Lertxundi A, Tardón A, Guxens M, Murcia M, Lopez-Espinosa MJ, Ballester F, on behalf of the INMA Project. 2016. Prenatal exposure to NO₂ and ultrasound measures of fetal growth in the Spanish INMA Cohort. Environ Health Perspect 124:235–242; http://dx.doi.org/10.1289/ehp.1409423

Address correspondence to C. Iñiguez, FISABIO, Avda, Cataluña No. 21, 46020 Valencia (Spain). Telephone: (34) 961925953. E-mail: [email protected]

We thank all the participants for their generous collaboration. A full roster of the INMA Project Investigators can be found at http://www.proyectoinma.org/presentacion​-inma/listado-investigadores/en_listado-​investigadores.html .

This study was funded by grants from the European Union: NEWGENERIS FP6-2003-Food-3-A-016320, FP7-ENV-2011 cod 282957, HEALTH.2010.2.4.5-1; and by grants from Spain: Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0031, and FIS-FEDER PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI04/2018, PI04/1436, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI08/1151, PI09/02647, PI09/02311, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/02429, PI14/0891, PI14/1687, and Miguel Servet CP11/00178 and MS13/00054), Conselleria de Sanitat Generalitat Valenciana, Generalitat de Catalunya (CIRIT 1999SGR 00241), Diputación Foral de Guipúzcoa (DFG/004), Departamento de Sanidad y Consumo Gobierno Vasco (2005111093), Obra Social Cajastur, and Oviedo University.

The authors declare they have no actual or potential competing financial interests.

Received: 3 November 2014 Accepted: 22 June 2015 Advance Publication: 26 June 2015 Final Publication: 1 February 2016

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