{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T04:19:49Z","timestamp":1770351589665,"version":"3.49.0"},"reference-count":53,"publisher":"American Academy of Pediatrics (AAP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:sec><jats:title>BACKGROUND AND OBJECTIVES:<\/jats:title><jats:p>Nicotine replacement therapy (NRT) is now being used as a smoking cessation aid during pregnancy, although little is known about fetal safety. We assessed the relationship between early pregnancy exposure to NRT or smoking with major congenital anomalies (MCA) in offspring.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>We studied 192\u2009498 children born in the United Kingdom between 2001 and 2012 with linked mother\u2013child primary care records. The absolute risks of MCAs in the NRT group (women prescribed NRT during the first trimester or 1 month before conception [and therefore likely consumed during the first trimester]) and odds ratios (ORs) and 99% confidence intervals (CIs) were compared with those of women who smoked during pregnancy and with a control group (women who neither smoked nor were prescribed NRT); logistic regression models adjusted for maternal morbidities that increase MCA risk were used for analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>MCA prevalence was 288 per 10\u2009000 live births (5535 children with \u22651 MCA). Maternal morbidities were most common in the NRT group (35%) followed by smokers (27%) and the control group (20%). Compared with the control group, adjusted ORs for MCAs in the NRT group and smokers were 1.12 (99% CI: 0.84\u20131.48) and 1.05 (99% CI: 0.89\u20131.23), respectively. The OR comparing the NRT group directly with smokers was 1.07 (99% CI: 0.78\u20131.47). There were no statistically significant associations between maternal NRT and system-specific anomalies except for respiratory anomalies (OR: 4.65 [99% CI: 1.76\u201312.25]; absolute risk difference: 3 per 1000 births), which was based on 10 exposed cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>For most system-specific MCAs, we found no statistically significant increased risks associated with maternal NRT prescribed during pregnancy, except for respiratory anomalies. Although this study is the largest published to date, NRT use in pregnancy remains rare; thus, the statistical power was limited. Higher morbidities in those women prescribed NRT may also be an explanatory factor. Nevertheless, absolute MCA risks were similar between women who smoked and those prescribed NRT during pregnancy.<\/jats:p><\/jats:sec>","DOI":"10.1542\/peds.2014-2560","type":"journal-article","created":{"date-parts":[[2015,4,7]],"date-time":"2015-04-07T00:41:08Z","timestamp":1428367268000},"page":"859-867","source":"Crossref","is-referenced-by-count":41,"title":["Nicotine Replacement Therapy in Pregnancy and Major Congenital Anomalies in Offspring"],"prefix":"10.1542","volume":"135","author":[{"given":"Nafeesa N.","family":"Dhalwani","sequence":"first","affiliation":[{"name":"Division of Epidemiology and Public Health, University of Nottingham, Clinical Sciences Building, Nottingham City Hospital, Nottingham, United Kingdom; and"},{"name":"Division of Primary Care, University of Nottingham, Queen\u2019s Medical Centre, Nottingham, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Szatkowski","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Public Health, University of Nottingham, Clinical Sciences Building, Nottingham City Hospital, Nottingham, United Kingdom; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Coleman","sequence":"additional","affiliation":[{"name":"Division of Primary Care, University of Nottingham, Queen\u2019s Medical Centre, Nottingham, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Fiaschi","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Public Health, University of Nottingham, Clinical Sciences Building, Nottingham City Hospital, Nottingham, United Kingdom; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laila J.","family":"Tata","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Public Health, University of Nottingham, Clinical Sciences Building, Nottingham City Hospital, Nottingham, United Kingdom; and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[2015,5,1]]},"reference":[{"key":"2021120907134390500_B1","volume-title":"Passive Smoking and Children\u2014A Report by the Tobacco Advisory Group","author":"Royal College of Physicians","year":"2010"},{"issue":"2","key":"2021120907134390500_B2","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1097\/00006534-200002000-00001","article-title":"Maternal cigarette smoking during pregnancy and the risk of having a child with cleft lip\/palate.","volume":"105","author":"Chung","year":"2000","journal-title":"Plast Reconstr Surg"},{"issue":"7","key":"2021120907134390500_B3","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/bdra.20461","article-title":"Maternal periconceptional smoking and alcohol consumption and risk for select congenital anomalies.","volume":"82","author":"Grewal","year":"2008","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"issue":"1","key":"2021120907134390500_B4","doi-asserted-by":"crossref","first-page":"e84715","DOI":"10.1371\/journal.pone.0084715","article-title":"Maternal snuff use and smoking and the risk of oral cleft malformations\u2014a population-based cohort study.","volume":"9","author":"Gunnerbeck","year":"2014","journal-title":"PLoS One"},{"issue":"2","key":"2021120907134390500_B5","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1097\/01.ede.0000254430.61294.c0","article-title":"Maternal smoking and environmental tobacco smoke exposure and the risk of orofacial clefts.","volume":"18","author":"Honein","year":"2007","journal-title":"Epidemiology"},{"issue":"5","key":"2021120907134390500_B6","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/humupd\/dmr022","article-title":"Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls.","volume":"17","author":"Hackshaw","year":"2011","journal-title":"Hum Reprod Update"},{"key":"2021120907134390500_B7","volume-title":"The Infant Feeding Survey 2010: Early Results","author":"Health and Social Care Information Centre","year":"2011"},{"key":"2021120907134390500_B8","unstructured":"Centers for Disease Control and Prevention. 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