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Background: We previously identified associations between trimester-specific NO2 exposures and reduced fetal growth in the Spanish INfancia y Medio Ambiente (INMA) project. Here, we use temporally refined exposure estimates to explore the impact of narrow (weekly) windows of exposure on fetal growth. Methods: We included 1,685 women from INMA with serial ultrasounds at 12, 20, and 34 gestational weeks. We measured biparietal diameter (BPD), femur length, and abdominal circumference (AC) and from them calculated estimated fetal weight (EFW). We calculated z-scores describing trajectories of each parameter during early (0-12 weeks), mid (12-20 weeks), and late (20-34 weeks) pregnancy, based on longitudinal growth curves from mixed-effects models. We estimated weekly NO2 exposures at each woman's residence using land-use regression models. We applied distributed lag nonlinear models to identify sensitive windows of exposure. We present effect estimates as the percentage change in fetal growth per 10 μg/m3 increase in NO2 exposure, and we calculated cumulative effect estimates by aggregating estimates across adjacent lags. Results: We identified weeks 5-12 as a sensitive window for NO2 exposure on late EFW (cumulative β = -3.0%; 95% CI = -4.1%, -1.9%). We identified weeks 6-19 as a sensitive window for late growth in BPD (cumulative β = -2.0%; 95% CI = -2.7%, -1.4%) and weeks 8-13 for AC (cumulative β = -0.68%; 95% CI = -0.97%, -0.40%). We found suggestive evidence that third trimester NO2 exposure is associated with increased AC, BPD, and EFW growth in late pregnancy. Conclusions: Our findings are consistent with the hypothesis that NO2 exposure is associated with alterations in growth of EFW, BPD, and AC dependent on the specific timing of exposure during gestation. This work was supported by grant R01ES028842 from NIH/NIEHS; grants Red INMA G03/176, CB06/02/004; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663, FIS-PI18/01142 incl. FEDER funds; Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051, CPII18/00018, and CP16/00128 from Instituto de Salud Carlos III, grant 1999SGR 00241from Generalitat de Catalunya-CIRIT, grant FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1 from the EU Commission, grant UGP-15-230, UGP-15-244, and UGP-15-249 from Generalitat Valenciana: FISABIO, grant 2005111093 from Alicia Koplowitz Foundation 2017, Department of Health of the Basque Government, grant DFG06/002 from the Provincial Government of Gipuzkoa, and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). We also acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.

While the epidemiologic literature suggests certain maternal occupational exposures may be associated with reduced measures of size at birth, the occupational literature employing fetal biometry data to assess fetal growth is sparse. The present study examines associations between maternal occupational exposures and ultrasound-measured fetal growth. We included 1,739 singleton pregnancies from the INfancia y Medio Ambiente (INMA) project (2003-2008). At 32 weeks of pregnancy, interviewers ascertained mothers' employment status and assessed job-related physical loads, work schedules, and job strain during pregnancy. Job titles were linked to a job-exposure matrix to estimate exposure to 10 endocrine disrupting chemical (EDC) groups. We calculated z-scores from longitudinal growth curves representing trajectories from 0-12, 12-20 and 20-34 gestational weeks for abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), and estimated fetal weight (EFW). Linear mixed models clustered by IMNA region (i.e., Gipuzkoa, Sabadell, Valencia) were used to examine associations between occupational exposures and fetal growth. Effect estimates are presented as percentage change in fetal growth. There was limited evidence of associations between work-related non-chemical stressors and fetal growth. We observed associations of similar magnitude between multiple EDC groups and decreased EFW trajectories during 20-34 gestational weeks (phthalates: -1.4% [-3.5, 0.6%]; alkylphenolic compounds (APCs): -1.1% [-2.3, 0.1%]; miscellaneous chemicals: -1.5% [-3.7, 0.8%]), while miscellaneous chemicals were associated with increased BPD from 12-20 weeks (2.1% [0.8, 3.5%]). Notably, 67% of women exposed to phthalates were hairdressers; 68% of women exposed to APCs worked as domestic cleaners. In conclusion, we found limited evidence that maternal occupational exposures impact fetal growth. Further research should consider the combined impact of multiple workplace exposures. This work was supported by grants from the National Institutes of Health/National Institute of Environmental Health Sciences (R01ES028842, PI: KWW), Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663, FIS-PI18/01142 incl. FEDER funds; Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051, CPII18/00018, and CP16/00128), Generalitat de Catalunya-CIRIT 1999SGR 00241, EU Commission (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249) and Conselleria d’Educació AICO/2020/285, and Alicia Koplowitz Foundation 2017, Department of Health of the Basque Government (2005111093), Provincial Government of Gipuzkoa (DFG06/002), and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). We also acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. JI, DGRdP, and GLD were partly supported by the Southwest Center for Occupational and Environmental Health (SWCOEH), the Centers for Disease Control and Prevention (CDC) National Institute for Occupational Safety and Health (NIOSH) Education and Research Center (T42OH008421) at The University of Texas Health Science Center at Houston (UTHealth) School of Public Health. KWW and ES were supported in part by the by the Gulf Coast Center for Precision Environmental Health (GC-CPEH) at Baylor College of Medicine (P30ES030285). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.