{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T14:35:20Z","timestamp":1773153320465,"version":"3.50.1"},"reference-count":25,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"unspecified","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH","award":["HD096468"],"award-info":[{"award-number":["HD096468"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate the association of paternal intake of antipsychotics, anxiolytics, hypnotics and sedatives, antidepressants, selective serotonin reuptake inhibitors (SSRIs) and (benzo)diazepines during the development of fertilising sperm with birth defects in offspring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Prospective registry-based cohort study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Total Danish birth cohort 1997\u20132016 using Danish national registries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>All 1\u2009201\u2009119 Danish liveborn singletons born 1997\u20132016 were eligible, 39\u2009803 (3.3%) of whom had at least one major birth defect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Exposure<\/jats:title><jats:p>Offspring were considered exposed if their father had filled at least one prescription in the relevant drug category during development of fertilising sperm (the 3\u2009months prior to conception).<\/jats:p><\/jats:sec><jats:sec><jats:title>Primary and secondary outcome measures<\/jats:title><jats:p>Primary outcome was the diagnosis, in the first year of life, of at least one major birth defect as categorised in the EUROCAT guidelines. Secondary outcome was the diagnosis, in the first year of life, of at least one major birth defect in any of the EUROCAT subcategories. Adjusted ORs (AORs) were calculated, along with their 95% CIs, adjusted for year, education, smoking status and age of the mother, and education, disposable income and age of the father.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study found weak or null associations between birth defects and selected drugs. Specifically, antidepressants (17\u2009827 exposed births) gave 3.5% birth defects (AOR 0.97 (0.89 to 1.05)). Diazepines, oxazepines, thiazepines and oxepines (as antipsychotics, 1633 offspring) gave 4.7% birth defects (AOR 1.22 (0.97 to 1.54)), attenuated to 1.13 when excluding by mothers\u2019 prescriptions. The study was well powered assuming 100% therapy adherence, while assuming 50% therapy adherence, the study remained well powered for the largest groups (SSRIs and antidepressants overall).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Antipsychotics, anxiolytics, hypnotics and sedatives, antidepressants, SSRIs and benzodiazepine-derived anxiolytics, when taken by the father during development of fertilising sperm, are generally safe with regard to birth defects.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2021-053946","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T16:55:15Z","timestamp":1648659315000},"page":"e053946","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Nervous system drugs taken by future fathers and birth defects in offspring: a prospective registry-based cohort study"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6518-1015","authenticated-orcid":false,"given":"Maarten","family":"Wensink","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina Kold","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels Erik","family":"Skakkeb\u00e6k","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rune","family":"Lindahl-Jacobsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Eisenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"2023030803131397000_12.3.e053946.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.07.034"},{"key":"2023030803131397000_12.3.e053946.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2009.04.039"},{"key":"2023030803131397000_12.3.e053946.3","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/j.urology.2013.12.004","article-title":"Comparison of the effect of sertraline with behavioral therapy on semen parameters in men with primary premature ejaculation","volume":"83","author":"Akasheh","year":"2014","journal-title":"Urology"},{"key":"2023030803131397000_12.3.e053946.4","doi-asserted-by":"publisher","DOI":"10.1038\/ijir.2011.35"},{"key":"2023030803131397000_12.3.e053946.5","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0027-5107(02)00090-8","article-title":"Induction of aneuploidy in male mouse germ cells detected by the sperm\u2013FISH assay: a review of the present data base","volume":"504","author":"Adler","year":"2002","journal-title":"Mutation Research\/Fundamental and Molecular Mechanisms of Mutagenesis"},{"key":"2023030803131397000_12.3.e053946.6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S1383-5718(00)00141-8","article-title":"Detection of aneuploidy in rodent and human sperm by multicolor fish after chronic exposure to diazepam","volume":"490","author":"Baumgartner","year":"2001","journal-title":"Mutat Res"},{"key":"2023030803131397000_12.3.e053946.7","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1177\/1403494820987468","article-title":"Paternal prescription medication before conception: a retrospective cohort study of all births in Denmark 1997-2017","volume":"49","author":"Wensink","year":"2021","journal-title":"Scand J Public Health"},{"key":"2023030803131397000_12.3.e053946.8","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.fertnstert.2019.12.026","article-title":"Association of preconception paternal health on perinatal outcomes: analysis of U.S. claims data","volume":"113","author":"Kasman","year":"2020","journal-title":"Fertil Steril"},{"key":"2023030803131397000_12.3.e053946.9","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dex267"},{"key":"2023030803131397000_12.3.e053946.10","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-018-0356-1"},{"key":"2023030803131397000_12.3.e053946.11","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-014-9930-3"},{"key":"2023030803131397000_12.3.e053946.12","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyw213"},{"key":"2023030803131397000_12.3.e053946.13","doi-asserted-by":"publisher","DOI":"10.1177\/1403494811401482"},{"key":"2023030803131397000_12.3.e053946.14","unstructured":"EUROCAT . EUROCAT central registry uou. European surveillance of congenital Anormalities (EUROCAT 2013). In: EUROCAT guide 1.4: instruction for the registration of congenital anomalies. 11, 2019. https:\/\/eu-rd-platform.jrc.ec.europa.eu\/sites\/default\/files\/Full_Guide_1_4_version_28_DEC2018.pdf"},{"key":"2023030803131397000_12.3.e053946.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2016.04.009"},{"key":"2023030803131397000_12.3.e053946.16","first-page":"1","article-title":"Multivariate imputation by Chained equations in R","volume":"45","author":"van Buuren","year":"2011","journal-title":"Journal of Statistical Software"},{"key":"2023030803131397000_12.3.e053946.17","unstructured":"Woods S . Generalized additive models, an introduction with R. 2 edn. New York: Chapman and Hall\/CRC, 2017."},{"key":"2023030803131397000_12.3.e053946.18","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/OGX.0000000000000405","article-title":"Risk factors for birth defects","volume":"72","author":"Harris","year":"2017","journal-title":"Obstet Gynecol Surv"},{"key":"2023030803131397000_12.3.e053946.19","first-page":"756","article-title":"Update on overall prevalence of major birth defects--Atlanta, Georgia, 1978-2005","volume":"57","author":"Rynn","year":"2008","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2023030803131397000_12.3.e053946.20","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmr022"},{"key":"2023030803131397000_12.3.e053946.21","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.88.11.1674"},{"key":"2023030803131397000_12.3.e053946.22","unstructured":"R Development Core Team . R: a language and environment for statistical computing: R foundation for statistical computing, 2020."},{"key":"2023030803131397000_12.3.e053946.23","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(90)90005-M"},{"key":"2023030803131397000_12.3.e053946.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41437-018-0111-0"},{"key":"2023030803131397000_12.3.e053946.25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2012.04426.x"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2021-053946","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T11:42:23Z","timestamp":1678275743000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2021-053946"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":25,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3,28]]},"published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1136\/bmjopen-2021-053946"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2021-053946","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3]]}}}