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A recently updated Cochrane Review of randomized controlled trials (RCTs) investigating impacts of NRT in pregnancy focuses primarily on efficacy data, but also reports adverse impacts from NRT. Here we identify and summarize NRT impacts on adverse pregnancy outcomes reported in non\u2010randomized controlled trials (non\u2010RCTs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Systematic reviews and meta\u2010analyses of RCTs and non\u2010RCT studies of NRT in pregnancy, with design\u2010specific risk of bias assessment and grading of recommendations, assessment, development and evaluations (GRADE) criteria applied to selected outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>Relevant Cochrane Review findings are reported alongside those from this new review. Seven RCTs were included; <jats:italic>n<\/jats:italic>\u00a0=\u00a02340. Nine meta\u2010analyses were performed; non\u2010statistically significant estimates indicated potentially reduced risk from NRT compared with smoking for mean birth weight, low birth weight, preterm birth, intensive care admissions, neonatal death, congenital anomalies and caesarean section and potentially increased risks for miscarriage and stillbirth. GRADE assessment for mean birth weight and miscarriage outcomes indicated \u2018low\u2019 confidence in findings.<\/jats:p><jats:p>Twenty\u2010three non\u2010RCTs were included; <jats:italic>n<\/jats:italic>\u00a0=\u00a0931\u2009163. Eleven large studies from five routine health\u2010care cohorts reported clinical outcomes; 12 small studies investigated mainly physiological outcomes within in\u2010patient women given NRT. Findings from meta\u2010analyses for congenital anomalies, stillbirth and preterm birth were underpowered and not in a consistent direction; GRADE assessment of confidence in findings was \u2018very low\u2019. Routine health\u2010care studies were of higher quality, but implications of reported findings were unclear as there was inadequate measurement and reporting of women's smoking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Available evidence from randomized controlled trials and non\u2010randomized comparative studies does not currently provide clear evidence as to whether maternal use of nicotine replacement therapy during pregnancy is harmful to the fetus.<\/jats:p><\/jats:sec>","DOI":"10.1111\/add.15185","type":"journal-article","created":{"date-parts":[[2020,7,4]],"date-time":"2020-07-04T10:17:48Z","timestamp":1593857868000},"page":"239-277","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Fetal safety of nicotine replacement therapy in pregnancy: systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6183-6475","authenticated-orcid":false,"given":"Lauren","family":"Taylor","sequence":"first","affiliation":[{"name":"Division of Primary Care, Faculty of Medicine and Health Sciences  University of Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravinder","family":"Claire","sequence":"additional","affiliation":[{"name":"Division of Primary Care, Faculty of Medicine and Health Sciences  University of Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7453-9138","authenticated-orcid":false,"given":"Katarzyna","family":"Campbell","sequence":"additional","affiliation":[{"name":"Division of Primary Care, Faculty of Medicine and Health Sciences  University of Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Coleman\u2010Haynes","sequence":"additional","affiliation":[{"name":"Division of Primary Care, Faculty of Medicine and Health Sciences  University of Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo","family":"Leonardi\u2010Bee","sequence":"additional","affiliation":[{"name":"Centre for Evidence Based Healthcare, Division of Epidemiology and Public Health, Clinical Sciences Building Phase 2 University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Chamberlain","sequence":"additional","affiliation":[{"name":"Judith Lumley Centre, La Trobe University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5928-5616","authenticated-orcid":false,"given":"Ivan","family":"Berlin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Sorbonne Universit\u00e9, Facult\u00e9 de m\u00e9decine\u2010H\u00f4pital Piti\u00e9\u2010Salpetri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary\u2010Ann","family":"Davey","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Monash University  Clayton Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Cooper","sequence":"additional","affiliation":[{"name":"Division of Primary Care, Faculty of Medicine and Health Sciences  University of Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7303-4805","authenticated-orcid":false,"given":"Tim","family":"Coleman","sequence":"additional","affiliation":[{"name":"Division of Primary Care, Faculty of Medicine and Health Sciences  University of Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2003.09.001"},{"key":"e_1_2_9_3_1","unstructured":"DiFranzaJR LewRA.Effect of maternal cigarette smoking on pregnancy complications and sudden infant death syndrome. 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