{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T18:03:58Z","timestamp":1779818638670,"version":"3.53.1"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009128","name":"Research for Patient Benefit Programme","doi-asserted-by":"publisher","award":["NIHR207172"],"award-info":[{"award-number":["NIHR207172"]}],"id":[{"id":"10.13039\/501100009128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Medication use in pregnancy is common and increasing. Pregnant women are often excluded from drug trials, therefore the safety to mother and baby of many medications used in pregnancy is unknown. Routine health data have been used to look for evidence of harm and safety of specific medications, but not to systematically look across all prescribed medications in pregnancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To systematically identify medications prescribed during pregnancy requiring further research into their potential harms to mother or baby.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We will describe trends in primary care prescribing in pregnancy over time, and socio-demographic patterning of prescribing, using data from pregnancies in the Clinical Practice Research Datalink (CPRD). We will identify and categorise maternal, fetal, and infant adverse outcomes reported in the CPRD and linked hospital and mortality data. We will use Bayesian signal detection models to analyse all medication\/outcome pairs to identify where an outcome occurs significantly more frequently in mothers prescribed a specific medication than in mothers not prescribed it. Potential confounders will not be accounted for at this stage. Published evidence on the identified medication\/outcome pairs will be reviewed and incorporated with the results from trends and signal detection analyses. These data will be used by Patient Involvement and Study Advisory Board workshops to prioritise medications for further research, with medications more commonly prescribed for underserved groups being given precedence. For three prioritised signals, cohort analyses will compare the occurrence of adverse outcomes in those prescribed compared to those not prescribed the medication of interest, adjusting for maternal morbidity, co-medications, and other measured confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This project will provide a list of medications used in pregnancy that should be prioritised for further safety research. Results of three detailed retrospective cohort studies will contribute to informed decision making for patients and clinicians. Study grant number: NIHR207172; CPRD accepted protocol number: 24_004518.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0349045","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T17:24:16Z","timestamp":1779816256000},"page":"e0349045","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Medicines prescribed in pregnancy: Protocol for a signal detection study using routinely collected data in England"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8318-8421","authenticated-orcid":true,"given":"Liza","family":"Bowen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3055-769X","authenticated-orcid":true,"given":"Hannah","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1099-8460","authenticated-orcid":true,"given":"Iain M.","family":"Carey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tess","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Baker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek G.","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0011-5636","authenticated-orcid":true,"given":"Pensee","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9272-2585","authenticated-orcid":true,"given":"Michael R.","family":"Perkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Barr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7164-612X","authenticated-orcid":true,"given":"Joan","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"issue":"3","key":"pone.0349045.ref001","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.therap.2020.07.002","article-title":"Drug prescriptions in French pregnant women between 2015 and 2016: A study in the EGB database","volume":"76","author":"M Araujo","year":"2021","journal-title":"Therapie"},{"issue":"9","key":"pone.0349045.ref002","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/pds.4577","article-title":"Trends in prescription drug use during pregnancy and postpartum in Norway, 2005 to 2015","volume":"27","author":"A Engeland","year":"2018","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"6","key":"pone.0349045.ref003","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0287111","article-title":"Monitoring medicine prescriptions before, during and after pregnancy in Italy","volume":"18","author":"F Fortinguerra","year":"2023","journal-title":"PLoS One"},{"issue":"1","key":"pone.0349045.ref004","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12916-022-02722-5","article-title":"Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019","volume":"21","author":"A Subramanian","year":"2023","journal-title":"BMC Med"},{"key":"pone.0349045.ref005","unstructured":"Department of Health and Social Care. Women\u2019s Health Strategy for England. 2022."},{"key":"pone.0349045.ref006","unstructured":"European Medicines Agency. Guideline on good pharmacovigilance practice (GVP): Product or Population-Specific considerations III: Pregnant and breastfeeding women. 2019."},{"key":"pone.0349045.ref007","author":"MHRA","year":"2021"},{"key":"pone.0349045.ref008","unstructured":"RAND Europe. Pregnancy Research Review: Policy Report. 2020."},{"key":"pone.0349045.ref009","unstructured":"ONS. Childbearing for women born in different years, England and Wales: 2020. 2022."},{"issue":"7","key":"pone.0349045.ref010","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1053\/j.semperi.2015.08.002","article-title":"Epidemiology of medications use in pregnancy","volume":"39","author":"M Ayad","year":"2015","journal-title":"Semin Perinatol"},{"key":"pone.0349045.ref011","unstructured":"NHS Business Services Authority. Medicines Used in Mental Health - England - 2015\/16 to 2022\/23. 2023."},{"key":"pone.0349045.ref012","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.b3999","article-title":"Explaining the rise in antidepressant prescribing: A descriptive study using the general practice research database","volume":"339","author":"M Moore","year":"2009","journal-title":"BMJ"},{"issue":"11","key":"pone.0349045.ref013","article-title":"Trend of antidepressants before, during, and after pregnancy across two decades-A population-based study","volume":"9","author":"Y Sun","year":"2019","journal-title":"Brain Behav"},{"issue":"5","key":"pone.0349045.ref014","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s40264-023-01291-7","article-title":"Core data elements for pregnancy pharmacovigilance studies using primary source data collection methods: Recommendations from the IMI ConcePTION project","volume":"46","author":"JL Richardson","year":"2023","journal-title":"Drug Saf"},{"issue":"6","key":"pone.0349045.ref015","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/pds.5584","article-title":"Methods to refine and extend a Pregnancy Register in the UK Clinical Practice Research Datalink primary care databases","volume":"32","author":"J Campbell","year":"2023","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"pone.0349045.ref016","author":"Clinical Practice Research Datalink","year":"2023"},{"issue":"2","key":"pone.0349045.ref017","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2021-055773","article-title":"Investigating the optimal handling of uncertain pregnancy episodes in the CPRD GOLD Pregnancy Register: A methodological study using UK primary care data","volume":"12","author":"J Campbell","year":"2022","journal-title":"BMJ Open"},{"issue":"7","key":"pone.0349045.ref018","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1002\/pds.4811","article-title":"Methods to generate and validate a Pregnancy Register in the UK Clinical Practice Research Datalink primary care database","volume":"28","author":"C Minassian","year":"2019","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"pone.0349045.ref019","unstructured":"Damase-Michel C a W, Beau AB, B\u00e9n\u00e9vent J, Hurault-Delarue C, Bromley RL, Dolk H, et al. D1.2 Core evidence elements for generating medication safety evidence for pregnancy using population-based data. 2021."},{"key":"pone.0349045.ref020","author":"A Clery","year":"2019"},{"issue":"2","key":"pone.0349045.ref021","article-title":"A chronological map of 308 physical and mental health conditions from 4 million individuals in the English National Health Service","volume":"1","author":"V Kuan","year":"2019","journal-title":"Lancet Digit Health"},{"issue":"1","key":"pone.0349045.ref022","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1186\/s12884-023-05598-2","article-title":"Adverse infant outcomes following low-risk pregnancies in England: A retrospective cohort study","volume":"23","author":"M Riley","year":"2023","journal-title":"BMC Pregnancy Childbirth"},{"key":"pone.0349045.ref023","author":"Joint Formulary Committee","year":"2025"},{"issue":"1","key":"pone.0349045.ref024","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/pds.668","article-title":"A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions","volume":"11","author":"EP van Puijenbroek","year":"2002","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"6","key":"pone.0349045.ref025","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s40264-018-00792-0","article-title":"A comparison study of algorithms to detect drug-adverse event associations: frequentist, bayesian, and machine-learning approaches","volume":"42","author":"M Pham","year":"2019","journal-title":"Drug Saf"},{"issue":"4","key":"pone.0349045.ref026","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s002280050466","article-title":"A Bayesian neural network method for adverse drug reaction signal generation","volume":"54","author":"A Bate","year":"1998","journal-title":"Eur J Clin Pharmacol"},{"issue":"21","key":"pone.0349045.ref027","doi-asserted-by":"crossref","first-page":"3740","DOI":"10.1002\/sim.2473","article-title":"Extending the methods used to screen the WHO drug safety database towards analysis of complex associations and improved accuracy for rare events","volume":"25","author":"GN Nor\u00e9n","year":"2006","journal-title":"Stat Med"},{"issue":"2","key":"pone.0349045.ref028","article-title":"Identification of misclassified pregnancy episodes in women of childbearing potential exposed to drugs with known teratogenic potential in the CPRD GOLD Pregnancy Register","volume":"33","author":"C Lee","year":"2024","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"pone.0349045.ref029","unstructured":"MHRA. Antiepileptic drugs: review of safety of use during pregnancy. 2021."}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0349045","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T17:24:21Z","timestamp":1779816261000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0349045"}},"subtitle":[],"editor":[{"given":"Katherine Demi","family":"Kokkinias","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0349045","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]}}}