PMID- 31546130 OWN - NLM STAT- MEDLINE DCOM- 20200430 LR - 20210110 IS - 1096-0953 (Electronic) IS - 0013-9351 (Print) IS - 0013-9351 (Linking) VI - 179 IP - Pt A DP - 2019 Dec TI - Maternal exposure to outdoor air pollution and congenital limb deficiencies in the National Birth Defects Prevention Study. PG - 108716 LID - S0013-9351(19)30513-4 [pii] LID - 10.1016/j.envres.2019.108716 [doi] AB - BACKGROUND: Congenital limb deficiencies (CLDs) are a relatively common group of birth defects whose etiology is mostly unknown. Recent studies suggest maternal air pollution exposure as a potential risk factor. AIM: To investigate the relationship between ambient air pollution exposure during early pregnancy and offspring CLDs. METHODS: The study population was identified from the National Birth Defects Prevention Study, a population-based multi-center case-control study, and consisted of 615 CLD cases and 5,701 controls with due dates during 1997 through 2006. Daily averages and/or maxima of six criteria air pollutants (particulate matter <2.5 mum [PM(2.5)], particulate matter <10 mum [PM(10)], nitrogen dioxide [NO(2)], sulfur dioxide [SO(2)], carbon monoxide [CO], and ozone [O(3)]) were averaged over gestational weeks 2-8, as well as for individual weeks during this period, using data from EPA air monitors nearest to the maternal address. Logistic regression was used to estimate odds ratios (aORs) and 95% confidence intervals (CIs) adjusted for maternal age, race/ethnicity, education, and study center. We estimated aORs for any CLD and CLD subtypes (i.e., transverse, longitudinal, and preaxial). Potential confounding by co-pollutant was assessed by adjusting for one additional air pollutant. Using the single pollutant model, we further investigated effect measure modification by body mass index, cigarette smoking, and folic acid use. Sensitivity analyses were conducted restricting to those with a residence closer to an air monitor. RESULTS: We observed near-null aORs for CLDs per interquartile range (IQR) increase in PM(10), PM(2.5), and O(3). However, weekly averages of the daily average NO(2) and SO(2), and daily max NO(2), SO(2), and CO concentrations were associated with increased odds of CLDs. The crude ORs ranged from 1.03 to 1.12 per IQR increase in these air pollution concentrations, and consistently elevated aORs were observed for CO. Stronger associations were observed for SO(2) and O(3) in subtype analysis (preaxial). In co-pollutant adjusted models, associations with CO remained elevated (aORs: 1.02-1.30); but aORs for SO(2) and NO(2) became near-null. The aORs for CO remained elevated among mothers who lived within 20 km of an air monitor. The aORs varied by maternal BMI, smoking status, and folic acid use. CONCLUSION: We observed modest associations between CLDs and air pollution exposures during pregnancy, including CO, SO(2), and NO(2), though replication through further epidemiologic research is warranted. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Choi, Giehae AU - Choi G AD - Department of Epidemiology, University of North Carolina, Chapel Hill, NC, United States. Electronic address: giehae.choi@unc.edu. FAU - Stingone, Jeanette A AU - Stingone JA AD - Department of Epidemiology, Columbia University, New York, NY, United States. FAU - Desrosiers, Tania A AU - Desrosiers TA AD - Department of Epidemiology, University of North Carolina, Chapel Hill, NC, United States. FAU - Olshan, Andrew F AU - Olshan AF AD - Department of Epidemiology, University of North Carolina, Chapel Hill, NC, United States. FAU - Nembhard, Wendy N AU - Nembhard WN AD - Department of Epidemiology, Fay Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States. FAU - Shaw, Gary M AU - Shaw GM AD - Stanford School of Medicine, Stanford, CA, United States. FAU - Pruitt, Shannon AU - Pruitt S AD - National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, United States; Oak Ridge Institute for Science and Education, Oak Ridge, TN, United States. FAU - Romitti, Paul A AU - Romitti PA AD - Department of Epidemiology, The University of Iowa, Iowa City, IA, United States. FAU - Yazdy, Mahsa M AU - Yazdy MM AD - Massachusetts Department of Health, Boston, MA, United States. FAU - Browne, Marilyn L AU - Browne ML AD - New York State Department of Health, Albany, NY, United States. FAU - Langlois, Peter H AU - Langlois PH AD - Texas Department of State Health Services, Austin, TX, United States. FAU - Botto, Lorenzo AU - Botto L AD - Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA. FAU - Luben, Thomas J AU - Luben TJ AD - Office of Research and Development, U.S. Environmental Protection Agency, RTP, NC, United States. CN - National Birth Defects Prevention Study LA - eng GR - P30 ES010126/ES/NIEHS NIH HHS/United States GR - U01 DD001223/DD/NCBDD CDC HHS/United States GR - P30 ES005605/ES/NIEHS NIH HHS/United States GR - T32 ES007018/ES/NIEHS NIH HHS/United States GR - U01 DD001231/DD/NCBDD CDC HHS/United States GR - U01 DD001224/DD/NCBDD CDC HHS/United States GR - U01DD001231/ACL/ACL HHS/United States GR - U01 DD001035/DD/NCBDD CDC HHS/United States GR - U01 DD001227/DD/NCBDD CDC HHS/United States GR - U01 DD001226/DD/NCBDD CDC HHS/United States GR - P30 ES009089/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190910 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 RN - 0 (Air Pollutants) RN - 0 (Particulate Matter) RN - 0UZA3422Q4 (Sulfur Dioxide) RN - 66H7ZZK23N (Ozone) RN - S7G510RUBH (Nitrogen Dioxide) SB - IM MH - *Air Pollutants MH - Air Pollution/*statistics & numerical data MH - Case-Control Studies MH - Congenital Abnormalities/*epidemiology/prevention & control MH - Female MH - Humans MH - Male MH - Maternal Exposure/*statistics & numerical data MH - Nitrogen Dioxide MH - *Ozone MH - Particulate Matter MH - Pregnancy MH - Sulfur Dioxide PMC - PMC6842662 MID - NIHMS1052448 OTO - NOTNLM OT - Air pollution OT - Carbon monoxide OT - Congenital limb deficiencies OT - Nitrogen dioxide OT - Sulfur dioxide COIS- Declarations of conflict of interests None. EDAT- 2019/09/24 06:00 MHDA- 2020/05/01 06:00 PMCR- 2019/12/01 CRDT- 2019/09/24 06:00 PHST- 2019/04/01 00:00 [received] PHST- 2019/07/28 00:00 [revised] PHST- 2019/09/01 00:00 [accepted] PHST- 2019/09/24 06:00 [pubmed] PHST- 2020/05/01 06:00 [medline] PHST- 2019/09/24 06:00 [entrez] PHST- 2019/12/01 00:00 [pmc-release] AID - S0013-9351(19)30513-4 [pii] AID - 10.1016/j.envres.2019.108716 [doi] PST - ppublish SO - Environ Res. 2019 Dec;179(Pt A):108716. doi: 10.1016/j.envres.2019.108716. Epub 2019 Sep 10.