{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T10:31:19Z","timestamp":1779877879084,"version":"3.53.1"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017596","name":"Bundesinstitut f\u00fcr Arzneimittel und Medizinprodukte","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>In analyzing pregnancy data concerning drug exposure in the first trimester, the risk of spontaneous abortions is of primary interest. For estimating the cumulative incidence function, the Aalen\u2013Johansen estimator is typically used, and competing risks such as induced abortion and livebirth are considered. However, the delayed study entry can lead to overly small risk sets for the first events. This results in large jumps in the estimated cumulative incidence function of spontaneous abortions or induced abortions using the Aalen\u2013Johansen estimator, and consequently in an overestimation of the probability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Several approaches account for early overly small risk sets. The first approach is conditioning on the event time being greater than the event time causing the large jump. Second, the events can be ignored by censoring them. Third, the events can be postponed until a large enough number is at risk. These three approaches are compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All approaches are applied using data of 54 lacosamide\u2010exposed pregnancies. The Aalen\u2013Johansen estimate of the probability of spontaneous abortion is 22.64%, which is relatively large for only three spontaneous abortions in the dataset. The conditional approach and the ignore approach have an estimated probability of 7.17%. In contrast, the estimate of the postpone approach is 16.45%. In this small sample, bootstrapped confidence intervals seem more accurate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In the analyses of pregnancy data with rare events, the postpone approach is favorable as no events are excluded. However, the approach that ignores early events has the narrowest confidence interval.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.5718","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T10:48:25Z","timestamp":1697626105000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["How to account for early overly small risk sets in the analysis of pregnancy outcome data?\u2014Comparison of different methods for stabilizing the Aalen\u2010Johansen estimator"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0528-348X","authenticated-orcid":false,"given":"Regina","family":"Stegherr","sequence":"first","affiliation":[{"name":"Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy, Institute of Clinical Pharmacology and Toxicology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Katrin","family":"Fietz","sequence":"additional","affiliation":[{"name":"Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy, Institute of Clinical Pharmacology and Toxicology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2451-4247","authenticated-orcid":false,"given":"Maria","family":"Hoeltzenbein","sequence":"additional","affiliation":[{"name":"Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy, Institute of Clinical Pharmacology and Toxicology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin 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