On- and Off-Label Atypical Antipsychotic Prescription Trends Across a Nine-Year Period Among Adolescents Pre- to Post-COVID-19.

OBJECTIVE: This study examined atypical antipsychotic prescribing by Food and Drug Administration (FDA) approved-use (on-label) status for adolescents before and during the COVID-19 pandemic. METHODS: Retrospective data were collected from electronic health records (EHRs) of adolescents aged 10-17 years in Kaiser Permanente Northern California. New outpatient atypical antipsychotic prescription orders during 2013-2021 were evaluated. Prescriptions were categorized as on-label if linked in EHRs to autism, psychosis, bipolar disorder, or Tourette's diagnoses; otherwise, they were potentially off-label (herein, off-label). Trend analysis of monthly prescribing rates assessed slope change at pandemic onset for the cohort and by sex and age groups. RESULTS: Among 5828 patients, 74.5% of new antipsychotic orders were off-label in 2021. Overall prescribing decreased significantly until early 2020 (slope = -0.045, P < .01) but then significantly increased through 2021 (post-March 2020 slope change = 0.211, P = .01). Off-label prescriptions increased at a similar rate during the COVID-19 time period, but on-label prescriptions did not change significantly. Males and younger adolescents (ages 10-14 years) showed significant decreases until early 2020, while females and older adolescents (ages 15-17 years) did not. Females and younger adolescents exhibited significant increases in overall and off-label prescribing rates following pandemic onset; older adolescents exhibited increases in overall prescriptions while males had no detectable changes. CONCLUSIONS: Antipsychotic prescribing declined slightly but then increased significantly following COVID-19 onset for overall and off-label prescriptions. Pandemic onset differentially impacted antipsychotic prescribing by sex and age, with overall and off-label prescribing driven by increases among female and younger adolescents.

Telehealth Collaborative Care Led by Clinical Pharmacists for People With Psychosis or Bipolar Disorder: A Propensity Weighted Comparison With Usual Psychiatric Care.

Objective: People with psychosis or bipolar disorder (severe and persistent mental illness [SPMI]) are at high risk for poor psychiatric and chronic illness outcomes, which could be ameliorated through improved health care quality. This study assessed whether a telehealth, collaborative care program managed by psychiatric clinical pharmacists (SPMI Population Care) was associated with improved health care quality for adults with SPMI in a large California health system.Methods: This retrospective cohort study used electronic health record data to compare 968 program enrollees at 6 demonstration sites (Population Care) to 8,339 contemporaneous patients with SPMI at 6 non-program sites (Usual Care). SPMI diagnoses were based on ICD-10-CM diagnostic codes. Primary outcomes were optimal psychotropic medication adherence, guideline-recommended glycemic screening, annual psychiatrist visit, and emergency department use. Difference-in-difference analyses assessed change in outcomes from 12 months pre- to 12 months post-enrollment using overlap weighting with high dimensional propensity scores to balance participant characteristics across groups. Participant data were collected from January 1, 2020, to June 30, 2022.Results: From pre- to post-enrollment, Population Care was associated with greater achievement of psychotropic medication adherence and glycemic screening (+6 and +9 percentage points), but unexpectedly with a decrease in annual psychiatrist visits (-6 percentage points) and no significant change in emergency department use, relative to Usual Care. More than 75% of Population Care participants attended an intake and ≥ 1 follow-up visits. Participants with psychosis (26% of sample) had similar results as those with bipolar disorder.Conclusions: Clinical pharmacist-led telehealth collaborative care has potential to improve psychopharmacologic treatment adherence and recommended disease preventive screening for people with psychosis or bipolar disorder.

Agreement Between Self-reports and Urine Toxicology Measures of Illicit Methamphetamine and Cocaine Use During Early Pregnancy.

OBJECTIVE: This study aimed to assess agreement between self-report and urine toxicology measures assessing use of 2 illicit simulants (methamphetamine and cocaine) during early pregnancy. METHODS: This cross-sectional study of 203,053 pregnancies from 169,709 individuals receiving prenatal care at Kaiser Permanente Northern California between January 1, 2011, and December 31, 2019, assessed agreement ( κ , sensitivity, and specificity) between self-reported frequency and urine toxicology measures of methamphetamine and cocaine early in pregnancy. RESULTS: Prenatal use of the illicit stimulants was rare according to toxicology (n = 244 [0.12%]) and self-report measures (n = 294 [0.14%]). Agreement between these measures was low ( κ < 0.20). Of the 498 positive pregnancies, 40 (8.03%) screened positive on both measures, 204 (40.96%) screened positive on toxicology tests only, and 254 (51.00%) screened positive by self-report only. Relative to toxicology tests, sensitivity of any self-reported use was poor with 16.39% (95% confidence interval [CI], 11.75%-21.04%) of pregnancies with a positive toxicology test self-reporting any use in pregnancy. Relative to self-report, sensitivity of toxicology tests was also poor with 13.61% (95% CI, 9.69%-17.52%) of pregnancies who self-reported any use having positive urine toxicology tests. The sensitivity improved slightly at higher frequencies of self-reported use: daily, 17.50% (95% CI, 5.72%-29.29%); weekly, 25.00% (95% CI, 11.58%-38.42%); and monthly or less, 11.06% (95% CI, 6.89%-15.23%). Specificity was high (>99%), reflecting the high negative rate of use. CONCLUSIONS: Findings suggest that using self-report and toxicology measures in combination likely provides the most accurate information on methamphetamine and cocaine use in early pregnancy. Findings also highlight the need to provide supportive nonstigmatizing environments in which pregnant individuals feel comfortable disclosing substance use without fear of punishment.

Patterns of Substance Use During Early Pregnancy and Associations With Behavioral Health Characteristics.

OBJECTIVES: The aims of the study are to identify patterns of early pregnancy substance use and to examine how these patterns relate to behavioral health conditions measured in early pregnancy. METHODS: We conducted a retrospective observational study (N= 265,274 pregnancies) screened for alcohol, cannabis, nicotine, pharmaceutical opioids, and stimulants during the first trimester via self-report and urine toxicology tests in Kaiser Permanente Northern California from January 1, 2012, to December 31, 2019. To identify patterns of prenatal substance use, we conducted latent class analysis. We then calculated the prevalence of depression, anxiety, intimate partner violence, and family drug use history for each prenatal substance use group and compared the prevalences by estimating prevalence ratios using modified Poisson regression, adjusting for sociodemographic characteristics. RESULTS: We identified the following 4 latent groups with different patterns of substance use: ( a ) predominantly alcohol and no other substances (9.30%), ( b ) predominantly cannabis and no other substances (4.88%), ( c ) predominantly nicotine and some pharmaceutical opioids (1.09%), and ( d ) high-polysubstance (alcohol, cannabis, nicotine, and stimulants; 0.36%); these pregnancies were compared with ( e ) no prenatal substance use (84.37%). The prevalence of all behavioral health conditions was elevated in all prenatal substance use groups compared with the no substance use group. Furthermore, the prevalence of depressive and anxiety disorders, intimate partner violence and family drug use history were greater in the high-polysubstance cluster than the alcohol and cannabis clusters. CONCLUSIONS: Results highlight the importance of screening and interventions for all types of substance use during early pregnancy and suggest a particularly high need to prioritize targeting early interventions to pregnant and reproductive age individuals with polysubstance use.

Current tobacco smoking and risk of SARS-CoV-2 infection and hospitalization: Evaluating the role of socio-demographic factors and comorbidities.

Our recently published study of >2.4 million adults in Northern California indicated that current versus never-tobacco smoking was associated with lower risk of SARS-CoV-2 infection and less severe coronavirus disease 2019 (COVID-19). We extended this research by evaluating whether these associations were moderated by socio-demographic factors and medical comorbidities. This retrospective cohort study of 1,885,826 adults with current or never-smoking status in Kaiser Permanente Northern California from 3/5/2020 (baseline) to 12/31/2020 (pre-vaccine) included electronic health record-based socio-demographics (sex, age, race/ethnicity, neighborhood deprivation index (NDI)) and medical comorbidities (obesity, cardiovascular conditions, diabetes, renal disease, respiratory conditions). We estimated the adjusted risk of SARS-CoV-2 infection and hospitalization (≤30 days of infection) associated with smoking status using Cox proportional hazard regression models. We estimated associations within subgroups of socio-demographics and comorbidities, and tested for effect modification using interaction terms. During the study, 35,627 patients had SARS-CoV-2 infection. Current versus never-smoking status was associated with lower adjusted rates of SARS-CoV-2 infection (aHR ranging from 0.51 to 0.89) and hospitalization (aHR ranging from 0.32 to 0.70) within nearly every socio-demographic and comorbidity subgroup. Statistically significant interactions showed that the magnitude of protection for SARS-CoV-2 infection varied by sex, age, race/ethnicity, NDI, cardiovascular conditions and diabetes, and for SARS-CoV-2 hospitalization by age and renal disease. Taken together, results indicated that while some socio-demographics and comorbidities moderated the associations, the lower risk of SARS-CoV-2 infection and hospitalization associated with current versus never-smoking status persisted among patients regardless of socio-demographics or comorbidities.

Cardiometabolic Monitoring and Sociodemographic and Clinical Characteristics of Youths Prescribed Antipsychotic Medications.

OBJECTIVE: This study examined time trends and patient characteristics related to guideline-recommended cardiometabolic risk factor monitoring among youths treated with antipsychotic medications. METHODS: This observational study assessed participant sociodemographic and clinical characteristics and year of antipsychotic medication initiation, with receipt of glycemic and lipid testing within 2 years of initiation as the primary outcome. Electronic health records and pharmacy data from Kaiser Permanente Northern California for 4,568 youths (ages 10-21 years) who began antipsychotic medication treatment during 2013-2017 were included. RESULTS: Mean±SD age of the sample was 17.0±3.0 years, 52% were male, and 50% were Asian American, Native Hawaiian, or Pacific Islander; Black; Latino; or another or unknown race-ethnicity. Overall, 54% of the sample completed glycemic and lipid monitoring within 2 years of medication initiation (41% within 1 year). With each study year, monitoring rates increased by 5% in this cohort, after the analyses were adjusted for participant factors (p=0.001). In the fully adjusted analysis, youths with a psychotic disorder were 23% more likely to receive cardiometabolic monitoring than those without a psychotic disorder or bipolar disorder (p<0.001). Monitoring was also more common among younger versus older adolescents and among those with risperidone (vs. quetiapine) medication, obesity, or more frequent use of outpatient health care. Youths with (vs. without) substance use disorder were 19% less likely to complete monitoring (p<0.001). CONCLUSIONS: Cardiometabolic monitoring increased modestly over time, but close to half of the studied youths did not receive glycemic or lipid testing. Additional clinical strategies may be needed to increase monitoring overall and among harder-to-reach youth subgroups.

Electroconvulsive Therapy Anesthetic Choice and Clinical Outcomes.

OBJECTIVE: Etomidate and methohexital are the 2 commonly used anesthetics for electroconvulsive therapy (ECT) in the United States. The objective of this study was to examine how anesthetic choice between etomidate and methohexital is associated with real-world clinical outcomes. METHODS: This naturalistic retrospective cohort study examined longitudinal electronic health records for 495 adult patients who received 2 or more ECT treatments from 2010 to 2019 in Kaiser Permanente North California, a large integrated health care system. Study outcomes included 12-month posttreatment depression remission as measured by the 9-item Patient Health Questionnaire, psychiatric and all-cause emergency department visits, and psychiatric and all-cause hospitalizations. RESULTS: Anesthetic choice was not significantly related to depression severity, emergency department visits, or psychiatric hospitalizations at 12 months after completing ECT. In exploratory analyses, we found that etomidate compared with methohexital was associated with higher rates of patient discomfort adverse effects-postictal agitation, phlebitis, and myoclonus (2.4% vs 0.4%; P < 0.001). CONCLUSIONS: We present the first large comparison of etomidate and methohexital as anesthetics for ECT and their associations with real-world outcomes. Our study showed no significant difference on depression remission, emergency department visits, or hospitalizations 12-months posttreatment. Thus, clinicians should focus on other patient or treatment characteristics when deciding on anesthetics for ECT. Further investigation is needed to confirm our exploratory findings that etomidate use was correlated with a higher rate of patient discomfort adverse effects relative to methohexital.

Tobacco Smoking and Risk of SARS-CoV-2 Infection and Disease Severity Among Adults in an Integrated Healthcare System in California.

INTRODUCTION: The relationship between tobacco smoking status and SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) severity is highly debated. We conducted a retrospective cohort study of >2.4 million adults in a large healthcare system to evaluate whether smoking is associated with SARS-CoV-2 infection and disease severity. AIMS AND METHODS: This retrospective cohort study of 2,427,293 adults in KPNC from March 5, 2020 (baseline) to December 31, 2020 (pre-vaccine) included smoking status (current, former, never), socio-demographics, and comorbidities from the electronic health record. SARS-CoV-2 infection (identified by a positive PCR test) and COVID-19 severity (hospitalization, ICU admission or death ≤ 30 days of COVID-19 diagnosis) were estimated in time-to-event analyses using Cox proportional hazard regression models adjusting for covariates. Secondary analyses examined COVID-19 severity among patients with COVID-19 using logistic regression. RESULTS: During the study, 44,270 patients had SARS-CoV-2 infection. Current smoking was associated with lower adjusted rates of SARS-CoV-2 infection (aHR = 0.64 95% CI: 0.61-0.67), COVID-19-related hospitalization (aHR = 0.48 95% CI: 0.40-0.58), ICU admission (aHR = 0.62 95% CI: 0.42-0.87), and death (aHR = 0.52 95% CI: 0.27-0.89) than never-smoking. Former smoking was associated with a lower adjusted rate of SARS-CoV-2 infection (aHR = 0.96 95% CI: 0.94-0.99) and higher adjusted rates of hospitalization (aHR = 1.10 95% CI: 1.03-1.08) and death (aHR = 1.32 95% CI: 1.11-1.56) than never-smoking. Logistic regression analyses among patients with COVID-19 found lower odds of hospitalization for current versus never-smoking and higher odds of hospitalization and death for former versus never-smoking. CONCLUSIONS: In the largest US study to date on smoking and COVID-19, current and former smoking showed lower risk of SARS-CoV-2 infection than never-smoking, while a history of smoking was associated with higher risk of severe COVID-19. IMPLICATIONS: In this cohort study of 2.4 million adults, adjusting for socio-demographics and medical comorbidities, current tobacco smoking was associated with a lower risk of both SARS-CoV-2 infection and severe COVID-19 illness compared to never-smoking. A history of smoking was associated with a slightly lower risk of SARS-CoV-2 infection and a modestly higher risk of severe COVID-19 illness compared to never-smoking. The lower observed COVID-19 risk for current versus never-smoking deserves further investigation. Results support prioritizing individuals with smoking-related comorbidities for vaccine outreach and treatments as they become available.

Closing the Care Gap for People with Severe and Persistent Mental Illness: Collaborative Care, Telehealth, and Clinical Pharmacy.

People with severe and persistent mental illness (SPMI) frequently struggle to maintain their recovery from recurring suicidality, psychosis, and debilitating mood episodes. They also face a high risk of chronic health conditions. Traditional - often short-term - psychiatric care is ill-equipped to meet the health needs of people with SPMI. Patients often require regular and sustained follow-up to support medication effectiveness and adherence and to screen for and treat cardiovascular disease and other common health risks. Kaiser Permanente Northern California has implemented a novel telehealth-based collaborative care program, SPMI Population Care, led by advanced practice clinical pharmacists, to improve the mental and physical health of its patients with SPMI. Although the individual program components of telehealth, collaborative care, and clinical pharmacy service have been employed successfully in the past for mental health care, the SPMI Population Care model combines the components and extends this approach to individuals at the most severe end of the psychiatric illness spectrum.

Trends in Self-reported and Biochemically Verified Cocaine and Methamphetamine Use Among Pregnant Individuals in Northern California, 2011-2019.

This cross-sectional study uses data from the Kaiser Permanente Northern California health care system with universal screening via self-report and urine toxicology at prenatal care entrance to examine trends in cocaine and methamphetamine use among pregnant individuals from 2011 to 2019.

Geographic Accessibility of Retail Cannabis in Northern California and Prenatal Cannabis Use During the COVID-19 Pandemic.

Importance: Prenatal cannabis use is associated with health risks for mothers and their children. Prior research suggests that rates of prenatal cannabis use in Northern California increased during the COVID-19 pandemic, but it is unknown whether increases varied with the local cannabis retail and policy environment. Objective: To test whether pandemic-related increases in prenatal cannabis use were greater among pregnant individuals with greater retail availability of cannabis around their homes or among those living in jurisdictions that allowed storefront retailers. Design, Setting, and Participants: A cross-sectional, population-based time series study used data from pregnancies in the Kaiser Permanente Northern California health care system screened for cannabis use before (January 1, 2019, to March 31, 2020) and during (April 1 to December 31, 2020) the early COVID-19 pandemic. Proximity to the nearest retailer and number of retailers within a 15-minute drive from one's home and local cannabis storefront retailer policy (banned vs permitted) were calculated. Interrupted time series models were fit using multiplicative and additive Poisson regression, adjusting for age and race and ethnicity. Exposures: The COVID-19 pandemic. Main Outcomes and Measures: Prenatal cannabis use based on universal urine toxicology tests conducted during early pregnancy at entrance to prenatal care. Results: The sample (n = 99 127 pregnancies) included 26.2% Asian or Pacific Islander, 6.8% Black, 27.6% Hispanic, 34.4% non-Hispanic White, and 4.9% other, unknown, or multiracial individuals, with a mean (SD) age of 30.8 (5.3) years. Prenatal cannabis use before (6.8%) and during (8.2%) the pandemic was associated with closer proximity to a retailer, greater retailer density, and residing in a jurisdiction that permitted vs banned retailers. There was a greater absolute increase in cannabis use from before to during the pandemic among those within a 10-minute drive (<10 minutes: adjusted rate difference [aRD], 0.93 cases/100 patients; 95% CI, 0.56-1.29 cases/100 patients; ≥10 minutes: aRD, 0.40 cases/100 patients; 95% CI, 0.12-0.68 cases/100 patients; interaction P = .02). Otherwise, relative and absolute rates increased similarly across categories of cannabis retailer proximity/density and local policy (interaction P > .05). Conclusions and Relevance: Prenatal cannabis use was more common among individuals living in areas with greater retail availability of cannabis. Although relative rates increased similarly during the pandemic regardless of local cannabis retail and policy environment, there was a larger absolute increase associated with living closer to a storefront cannabis retailer. Continued monitoring of local cannabis policy, the retail environment, and prenatal cannabis use is needed.

Electronic cigarette use and risk of COVID-19 among young adults without a history of cigarette smoking.

It is unknown whether use of e-cigarettes increases susceptibility to COVID-19. In a large clinical sample of young adults, we evaluated whether current or ever e-cigarette use was associated with polymerase chain reaction (PCR)-confirmed COVID-19. To address the confounding of combustible smoking, the sample was restricted to never smokers. This retrospective cohort study analyzed data from the electronic health records of 74,853 young adults (aged 18-35 years), without a history of cigarette smoking, who were screened for e-cigarette use (current, former, never) in the Kaiser Permanente Northern California (KPNC) healthcare system from 3/5/2020 (baseline) to 11/30/2020 (pre-vaccine). COVID-19 risk was estimated in time-to-event analyses using multivariable Cox proportional hazard regression models, adjusted for socio-demographics and medical comorbidities. E-cigarette status in the cohort was: 1.6% current, 1.2% former, and 97.2% never. During follow-up, 1965 (2.6%) patients acquired COVID-19. We did not find evidence that current (vs never) e-cigarette use was associated with risk of COVID-19 (aHR = 1.12 95%CI:0.77-1.62). However, we did find suggestive evidence that former (versus never) e-cigarette use may be associated with greater risk of COVID-19 (aHR = 1.39 95%CI:0.98-1.96). While e-cigarette use is associated with health risks for young adults, results from this study suggest that current use of e-cigarettes may not increase susceptibility for COVID-19 among young adults who have never smoked cigarettes.

Association of Pregnancy Intentions With Substance Use During Early Pregnancy.

OBJECTIVES: The goal of this study was to evaluate the association between pregnancy intentions and substance use in early pregnancy among pregnant women receiving prenatal care in a large, integrated healthcare system. METHODS: The sample comprised 29,787 Kaiser Permanente Northern California pregnant women (12.1% aged <25, 36.4% non-Hispanic White) screened for prenatal substance use in 2018 via a self-reported questionnaire and urine toxicology test given as part of standard prenatal care (at ∼8 weeks gestation). Multivariable logistic regression models tested for associations of pregnancy intentions with prenatal substance use (any use and specific substances) by self-report and/or a positive urine toxicology test. RESULTS: Adjusting for covariates, women with an unintended pregnancy (23.9% of the sample) had higher odds of any prenatal substance use than women with an intended pregnancy (28.8% vs 16.1%; adjusted odds ratio [aOR] = 1.80, 95% confidence interval [CI]:1.67-1.93). Having an unintended pregnancy was also associated with higher odds of using alcohol (14.4% vs 10.4%; aOR = 1.73, 95%CI:1.59-1.89), cannabis (15.6% vs 5.6%; aOR = 1.91, 95%CI:1.73-2.11), nicotine (3.8% vs 1.3%; aOR = 2.33, 95%CI:1.92-2.82), pain medication (2.3% vs 1.2%; aOR = 1.64, 95%CI:1.32-2.03), and stimulants (0.8% vs 0.3%; aOR = 1.85, 95%CI:1.23-2.79) early in pregnancy. DISCUSSION: Having an unintended pregnancy was associated with higher odds of substance use during early pregnancy. Connecting women of reproductive age with health education about pregnancy prevention and recognition of early signs of pregnancy, effective contraception, and early screening and interventions for prenatal substance use may help to reduce prenatal substance use and its associated consequences.

Psychotropic medication prescribing during the COVID-19 pandemic.

ABSTRACT: This study examined changes in psychotropic medication use associated with the early months of the coronavirus disease 2019 (COVID-19) pandemic. Using Kaiser Permanente Northern California electronic health records, the authors identified adult patients with fills for psychotropic medications and a non-psychotropic comparator (statins) in the 13 weeks before and after the first-known COVID-19-related death in California (March 4, 2020). Generalized estimating equations were used to derive relative risk ratios (RRR) for medication fills compared with the prior year. Analyses were stratified by new and continued fills and patient characteristics. Among 2,405,824 patients, the mean (SD) age was 49.8 (17.9) years; 52.9% were female; 47.9% identified as White; 8.0% and 7.9% had anxiety and depression disorder diagnoses, respectively. Accounting for secular trends, in the 13 weeks following March 4, 2020, there were increased fills for trazodone (RRR = 1.03, 95% CI = 1.02, 1.04), decreased fills for benzodiazepines (RRR = 0.95, 95% CI = 0.94, 0.96) and hypnotics (RRR = 0.97, 95% CI = 0.96, 0.99), and stable fills for antidepressants (RRR = 1.00, 95% CI = 0.99, 1.00). Relative rates of new fills decreased across most medication classes and continued fills either remained stable or demonstrated non-clinically significant decreases. Patients aged ≥65 years demonstrated decreased fills for most medication classes. In the first 13 weeks of the COVID-19 pandemic, fills for most psychotropic medications remained constant or showed small changes relative to the previous year. Continued (compared with new) fills accounted for observed increases in some medication classes. Older adults demonstrated decreased fills of most medications.

Premature mortality associated with severe mental illness or substance use disorder in an integrated health care system.

OBJECTIVE: Research has reported shortened lifespans (by 15-30 years) for those with severe mental illness (SMI) or substance use disorder (SUD), particularly among public mental health treatment consumers. We assessed SMI- and SUD-associated mortality in the understudied setting of a large, nonprofit integrated health care system. METHOD: This retrospective cohort study examined 2010-2017 health system and death records for 564,592 adult patients. Half had SMI/SUD diagnosis; half were a demographically matched comparison group without SMI, other mental health, or SUD diagnoses. We estimated mortality risks, adjusting for demographic and physical health factors. RESULTS: Having SMI or SUD was associated with higher odds of death (adjusted odds ratio = 1.87) and an average 6.3 years of earlier death relative to comparison individuals. Co-occurring SMI and SUD conferred higher mortality risk from major natural and unnatural causes than did SMI with no SUD. CONCLUSIONS: Some indicators of premature mortality were lower than those reported for U.S. public mental health consumers, but risk level varied widely by diagnosis. While patients' having insurance and broad access to care may lower risk, access to care may be insufficient to overcome the many patient-, provider-, and system-level factors contributing to poor physical health in SMI and SUD.

The 2nd to 4th digit length ratio (2D:4D) among children of Seveso women exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

BACKGROUND: Exposure to endocrine-disrupting chemicals (EDCs) during sensitive developmental windows, such as in utero, may influence disease later in life but direct measurement of fetal hormones is not feasible. The ratio of the length of the second finger digit to the fourth digit (2D:4D), a sexually dimorphic trait, is a biomarker of androgen levels and the androgen/estrogen balance in utero. However, it is unclear whether in utero EDC exposure might alter 2D:4D ratio. AIMS: We examined 2D:4D ratio in Seveso children in relation to in utero exposure to a potent EDC, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) using linear regression. STUDY DESIGN: The Seveso Women's Health Study (SWHS) is a historical cohort study, following the health of women exposed to TCDD during a 1976 explosion in Seveso, Italy. Individual-level TCDD was measured for SWHS in serum collected soon after the accident. In 2014, the SWHS children born after the explosion were enrolled in the Seveso Second Generation Study. SUBJECTS: 594 SWHS children born post-explosion to 397 mothers. OUTCOME MEASURES: Right hand 2D:4D ratio. RESULTS: On average, 2D:4D ratio for males was significantly lower than for females (p < 0.05). Overall, in utero TCDD exposure, either as maternal initial serum TCDD concentration or as TCDD extrapolated to pregnancy was not significantly associated with 2D:4D ratio in Seveso children. Results from all adjusted sensitivity analyses remained non-significant. CONCLUSIONS: Our results suggest in utero exposure to TCDD is not associated with alteration in 2D:4D ratio.