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prenatal alcohol exposure (PAE) associated with clinically significant adverse effects on cognitive and behavioral function. We used benchmark dose analysis to address this issue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Benchmark dose analyses were performed on composite cognitive function scores derived from data obtained at school age, adolescence, and early adulthood from 2227 participants from six prospective, longitudinal cohorts, whose mothers were interviewed about their alcohol and drug use during pregnancy or shortly thereafter. We compared single\u2010predictor models based on average alcohol consumed per day during pregnancy with a two\u2010predictor, semiparametric model based on (1) average alcohol dose per drinking occasion and (2) drinking frequency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our two\u2010predictor model showed that at lower levels of drinking frequency, a relatively high dose\/occasion is required for an increased risk of poor intellectual function, whereas at higher levels of drinking frequency, a lower dose\/occasion is sufficient to increase that risk. In addition, lower doses\/occasion were associated with clinically meaningful adverse effects in participants born to older than to younger mothers. The single\u2010predictor models proved less adequate because the dose\/occasion for a substantial proportion of participants exposed at the benchmark doses generated by those models was too low to increase the risk of clinically significant effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Given that the cognitive and behavioral deficits seen in FASD resemble those also seen in a range of other disorders, whether the patient's PAE is sufficient to increase the risk of clinically meaningful impairment is a critical element in an FASD diagnosis. Accurate diagnosis is needed to determine which patients warrant interventions that have been shown to be effective in remediating PAE\u2010related neurobehavioral impairment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70208","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T02:15:11Z","timestamp":1765592111000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Levels and patterns of prenatal alcohol exposure associated with increased risk of a clinically meaningful adverse effect on cognitive function"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8271-280X","authenticated-orcid":false,"given":"Joseph L.","family":"Jacobson","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Neurosciences Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tugba","family":"Akkaya\u2010Hocagil","sequence":"additional","affiliation":[{"name":"Department of Statistics and Actuarial Science University of Waterloo  Waterloo Ontario Canada"},{"name":"Department of Biostatistics, School of Medicine Ankara University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9768-2671","authenticated-orcid":false,"given":"Sandra W.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neurosciences Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1554-6914","authenticated-orcid":false,"given":"R. 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