Introduction and Objective: Youth type 2 diabetes (T2D) rates have risen globally. Preconception and pregnancy are sensitive periods for later T2D risk, yet contributing exposures remain unclear. We examined associations between maternal and pregnancy factors and early-onset T2D in the Predictors of Adverse Cardiometabolic Problems in Adolescents and Young Adults (PAPAYA) study at Kaiser Permanente Northern California (KPNC). Methods: This retrospective cohort included 303,037 individuals born at KPNC in 2003-2011. Maternal (education, age, parity, Medicaid status, pre-pregnancy BMI and diabetes) and pregnancy (gestational diabetes, preeclampsia, preterm birth, delivery mode) factors were obtained from electronic health records and birth certificates. Early-onset T2D (ages 10-21; N=453) was identified via the KPNC Diabetes Registry. Cox proportional hazards models estimated hazard ratios adjusting for confounders. Results: The cohort was 48.8% female and racially diverse (37.7% White, 25.5% Hispanic, 19.6% Asian/Pacific Islander, 7.0% Black, 0.3% Native American, 9.9% Other). Associations were significant in all models except preterm birth and delivery mode, with strongest effect estimates for pre-pregnancy BMI and diabetes (see Table). Conclusion: Several maternal sociodemographic, pre-pregnancy, and pregnancy factors were associated with early-onset T2D, providing targets for early-life interventions. Disclosure S. Daredia: None. S. Aghaee: None. J. Acker: None. J.Y. Liu: None. C.J. Huang: None. A. Karter: Research Support; Current; Dexcom, Inc. A. Kubo: None. J. Deardorff: None. Funding National Heart Lung and Blood Institute (1R01HL177516-01); National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK139116-01A1)

Introduction and Objective: Rates of type 2 diabetes (T2D) among adolescents and young adults (AYA; 10-30 years) are rising, yet risk among disaggregated Asian American (AsA), Native Hawaiian and Pacific Islander (NHPI) groups is poorly described. We estimated standardized AYA T2D prevalence within a large integrated health system. Methods: Retrospective cohort study (PAPAYA), using data from Kaiser Permanente Northern California electronic health records. T2D was identified using validated algorithms. The 2024 T2D prevalence was calculated by racial and ethnic group and age- and sex-standardized to the 2020 US census population. Results: As of 12/31/2024, 5,140 AYA had prevalent T2D (57% female; 12% age 10-19; 88% age 20-30). Marked heterogeneity was observed (Figure 1): NHPI and Filipino AYA had the highest prevalence (13.2 and 12.5 per 1000, respectively), exceeding rates in Black, Hispanic, and Native American AYA (8.8-9.4 per 1000), groups traditionally considered at highest risk. T2D prevalence among Filipinos was elevated despite lower mean BMI. Conclusion: T2D burden varies across AsA and NHPI subgroups, sometimes exceeding that of other high-risk groups. Findings highlight the importance of disaggregating AsA and NHPI to identify high risk groups, and the need to refine screening guidelines and clinical risk assessment in these populations. Disclosure A. Kubo: None. J. Deardorff: None. S. Srinivasan: Research Support; Current; Abbott, Eli Lilly and Company. J.Y. Liu: None. J. Acker: None. S. Daredia: None. C.J. Huang: None. S. Negriff: None. A. Kanaya: None. A.J. Karter: Research Support; Current; Dexcom, Inc. Funding National Institutes of Health (R01DK139116)

Introduction and Objective: The growing burden of type 2 diabetes (T2D) in adolescents and young adults (AYAs) has highlighted changing diabetes patterns at younger ages. We determined changes in prevalence of type 1 diabetes (T1D) and T2D across the adolescent and young adult ages and examined differences across racial and ethnic groups. Methods: We analyzed 2024 electronic health record data from 783,801 AYAs aged 10-30 years with prevalent diabetes from Kaiser Permanente Northern California as part of the Predictors of Adverse Cardiometabolic Problems in Adolescents and Young Adults (PAPAYA) Study. Diabetes type was classified using a validated algorithm. We calculated the proportion of T1D and T2D cases by age and race/ethnicity across four age categories (10-15, 16-20, 21-25 and 26-30). Results: The prevalence of T1D and T2D among KPNC members aged 10-30 years was 4.32 and 6.56/1,000 respectively. Overall, T1D was more common than T2D (3.28 vs 1.04/1000) in early adolescence, but T2D increased steadily with age, becoming the more common type by ages 21-25 (T1D: 6.67 vs T2D: 4.97/1000) (Fig 1a). Earlier T2D predominance was evident in all non-White groups (Fig 1b-1i). Conclusion: In this diverse, real-world cohort, we observed an early and progressive relative rise in T2D that differed markedly by race and ethnicity. These findings underscore the need for screening and clinical strategies that reflect this shifting epidemiology. Disclosure S. Srinivasan: Research Support; Current; Abbott, Eli Lilly and Company. A. Karter: Research Support; Current; Dexcom, Inc. J.Y. Liu: None. C.J. Huang: None. J. Acker: None. S. Daredia: None. J. Deardorff: None. S. Negriff: None. A. Kanaya: None. A. Kubo: None. Funding National Institutes of Health (R01DK139116)

PURPOSE:To examine the associations between adverse childhood experiences (ACEs) scores from routine screenings in pediatric checkups and timing of puberty in a diverse cohort of adolescents. METHODS:A retrospective cohort study of 52,573 pediatric members of Kaiser Permanente Northern California, an integrated healthcare delivery system. Exposure was the total ACEs score, determined using caregiver- and self-reported scores across all well-child visits, and categorized into 0, 1-3, 4-6, or 7-10 ACEs. Outcomes were age at menarche and pubertal onset, using physician-assessed Sexual Maturity Ratings. RESULTS:Girls with ACEs had a substantially higher risk of earlier menarche and pubertal onset compared to those without ACEs. There were no associations between ACEs and boys' pubertal timing. DISCUSSION:These results highlight the importance of screening for ACEs in a clinical setting to address adolescents' psychological well-being and healthy lifestyle habits, which in turn may prevent adverse health outcomes associated with early puberty.

ImportanceEarlier puberty is associated with adverse health outcomes, such as mental health issues in adolescence and cardiometabolic diseases in adulthood. Despite rapid growth of the Asian American, Native Hawaiian, and Pacific Islander populations in the US, limited research exists on their pubertal timing, potentially masking health disparities.ObjectiveTo examine pubertal timing among Asian American, Native Hawaiian, and Pacific Islander children and adolescents by disaggregating ethnic subgroups.Design, Setting, and ParticipantsThis retrospective cohort study included Asian American, Native Hawaiian, and Pacific Islander youths aged 5 to 18 years assessed for pubertal development at Kaiser Permanente Northern California, a large, integrated health care delivery system. Follow-up occurred from March 2005, through December 31, 2019. Data were analyzed in October 2023.ExposureRace and ethnicity, categorized into 11 ethnic subgroups: Asian Indian, Chinese, Filipino, Japanese, Korean, Native Hawaiian and Pacific Islander, Other South Asian, Other Southeast Asian, Vietnamese, multiethnic, and multiracial.Main Outcomes and MeasuresPubertal timing was determined using physician-assessed sexual maturity ratings (SMRs). Outcomes included the median age at transition from SMR 1 (prepubertal) to SMR 2 or higher (pubertal) for onset of genital development (gonadarche) in boys, breast development (thelarche) in girls, and pubic hair development (pubarche) in both boys and girls.ResultsIn this cohort of 107 325 Asian American, Native Hawaiian, and Pacific Islander children and adolescents (54.61% boys; 12.96% Asian Indian, 22.24% Chinese, 26.46% Filipino, 1.80% Japanese, 1.66% Korean, 1.96% Native Hawaiian and Pacific Islander, 0.86% Other South Asian, 3.26% Other Southeast Asian, 5.99% Vietnamese, 0.74% multiethnic, and 22.05% multiracial), the overall median ages for girls’ pubarche and thelarche were 10.98 years (95% CI, 10.96-11.01 years) and 10.13 years (95% CI, 10.11-10.15 years), respectively. For boys’ pubarche and gonadarche, median ages were 12.08 years (95% CI, 12.06-12.10 years) and 11.54 years (95% CI, 11.52-11.56 years), respectively. Differences between subgroups with earliest and latest median age at onset were 14 months for girls’ pubarche, 8 months for thelarche, 8 months for boys’ pubarche, and 4 months for gonadarche. In general, Asian Indian, Native Hawaiian and Pacific Islander, and Other South Asian subgroups had the earliest ages at onset across pubertal markers, while East Asian youths exhibited the latest onset. Restricting to those with healthy body mass index did not substantially change the findings.Conclusions and RelevanceIn this cohort study of Asian American, Native Hawaiian, and Pacific Islander children and adolescents, pubertal timing varied considerably across ethnic subgroups. Further investigation is warranted to assess whether these differences contribute to observed health disparities in adulthood, such as type 2 diabetes and cardiovascular diseases.

Key Points Question Are neighborhood economic and racial privilege associated with adolescent depressive symptoms, suicidality, and racial and ethnic disparities? Findings In this cohort study of 34 252 adolescents aged 12 to 16 years, lower neighborhood privilege was associated with greater risks of depressive symptoms and suicidality independently of individual-level sociodemographic characteristics. Additionally, adjusting for neighborhood privilege was associated with reduced mental health disparities affecting Black and Hispanic adolescents. Meaning The findings suggest that inequitable neighborhood contexts shaped by structural racism contribute to disparities in adolescent mental health.

Purpose: Early puberty is associated with adverse health outcomes over the life course, and Black and Hispanic girls experience puberty earlier than girls of other racial/ethnic backgrounds. Neighborhood racial and economic privilege may contribute to these disparities by conferring differential exposure to mechanisms (e.g., stress, obesity, endocrine disruptors) underlying early puberty. We examined as-sociations between neighborhood privilege, measured by the Index of Concentration at the Extremes (ICE), and age at pubic hair onset (pubarche) and breast development onset (thelarche) in a large multiethnic cohort.Methods: A cohort of 46,299 girls born 2005-2011 at Kaiser Permanente Northern California medical facilities were followed until 2021. Pubertal development was assessed routinely by pe-diatricians using the Sexual Maturity Rating scale. ICE quintiles for race/ethnicity, income, and income thorn race/ethnicity were calculated using American Community Survey 2010 5-year estimates and linked to census tract at birth. We fit multilevel Weibull regression models accommodating left, right, and interval censoring for all analyses.Results: ICE measures were monotonically associated with pubertal onset, with the strongest associations observed for ICE-race/ethnicity. Adjusting for maternal education, age at delivery, and parity, girls from the least versus most privileged ICE-race/ethnicity quintiles were at increased risk for earlier pubarche (hazard ratio: 1.30, 95% confidence interval: 1.21, 1.38) and thelarche (hazard ratio: 1.45, 95% confidence interval: 1.36, 1.54). These associations remained significant after adjusting for girls' race/ethnicity and childhood body mass index. Additionally, adjustment for ICE partially attenuated Black-White and Hispanic-White disparities in pubertal onset.Discussion: Neighborhood privilege may contribute to pubertal timing and related disparities.(c) 2022 Society for Adolescent Health and Medicine. All rights reserved.

Purpose: Children of mothers with prenatal depression have elevated risk for depression later in life. Pregnant women are hesitant to use antidepressants due to fear of adverse fetal effects. To inform prevention, this study examined associations between maternal prenatal depression and antidepressant use, and adolescent depressive symptoms and suicidality.Patients and Methods: Prospective data from 74,695 mother-adolescent dyads from the Kaiser Permanente Northern California integrated healthcare delivery system were used. Three prenatal exposure groups were examined: maternal depression and antide-pressants (Med); depression and no antidepressants (No-Med); neither depression nor antidepressants (NDNM). Adolescent depressive symptoms (Patient Health Questionnaire-2 score >= 3) and suicidality were assessed for 12-to 18-year-olds. Associations were analyzed using mixed effects logistic regression, adjusted for confounders.Results: Maternal prenatal depression was associated with higher odds of adolescent depressive symptoms (Med odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.23-1.84; No-Med OR: 1.59, CI: 1.34-1.88) and suicidality (Med OR: 2.36, CI: 1.67-3.34; No-Med OR: 1.54, CI: 1.10-2.14) compared to no prenatal depression (NDNM). Adolescents exposed to prenatal depression and antidepressants were not at greater odds of depressive symptoms (Med OR: 0.95, CI: 0.74-1.21) compared to those not exposed to antidepressants (No-Med). However, they showed non-significant but greater odds of suicidality (Med OR: 1.54, CI: 0.99-2.39).Conclusion: Our findings suggest that maternal prenatal depression is associated with adolescent depressive symptoms and suicidality, and that exposure to antidepressants in utero does not increase risk of depressive symptoms, specifically. While not statistically significant, the increased odds of suicidality among adolescents exposed to antidepressants suggest a possible association; however, further investigation is needed. After replication, the findings of this study may inform shared clinical decision-making when considering options regarding antidepressant use for the treatment of maternal prenatal depression.

In 2017–2019, the March of Dimes convened a workgroup with biomedical, clinical, and epidemiologic expertise to review knowledge of the causes of the persistent Black-White disparity in preterm birth (PTB). Multiple databases were searched to identify hypothesized causes examined in peer-reviewed literature, 33 hypothesized causes were reviewed for whether they plausibly affect PTB and either occur more/less frequently and/or have a larger/smaller effect size among Black women vs. White women. While definitive proof is lacking for most potential causes, most are biologically plausible. No single downstream or midstream factor explains the disparity or its social patterning, however, many likely play limited roles, e.g., while genetic factors likely contribute to PTB, they explain at most a small fraction of the disparity. Research links most hypothesized midstream causes, including socioeconomic factors and stress, with the disparity through their influence on the hypothesized downstream factors. Socioeconomic factors alone cannot explain the disparity's social patterning. Chronic stress could affect PTB through neuroendocrine and immune mechanisms leading to inflammation and immune dysfunction, stress could alter a woman's microbiota, immune response to infection, chronic disease risks, and behaviors, and trigger epigenetic changes influencing PTB risk. As an upstream factor, racism in multiple forms has repeatedly been linked with the plausible midstream/downstream factors, including socioeconomic disadvantage, stress, and toxic exposures. Racism is the only factor identified that directly or indirectly could explain the racial disparities in the plausible midstream/downstream causes and the observed social patterning. Historical and contemporary systemic racism can explain the racial disparities in socioeconomic opportunities that differentially expose African Americans to lifelong financial stress and associated health-harming conditions. Segregation places Black women in stressful surroundings and exposes them to environmental hazards. Race-based discriminatory treatment is a pervasive stressor for Black women of all socioeconomic levels, considering both incidents and the constant vigilance needed to prepare oneself for potential incidents. Racism is a highly plausible, major upstream contributor to the Black-White disparity in PTB through multiple pathways and biological mechanisms. While much is unknown, existing knowledge and core values (equity, justice) support addressing racism in efforts to eliminate the racial disparity in PTB.

BACKGROUND:Fundamental cause theory posits that social conditions strongly influence the risk of health risks. This study identifies risk mechanisms that social conditions associated with socioeconomic status (SES) and race/ethnicity shape in the production of colorectal cancer (CRC) mortality.METHODS:Two large datasets in the United States examining behavioral and medical preventive factors (N = 4.63-million people) were merged with population-level mortality data observing 761,100 CRC deaths among 3.31-billion person-years of observation to examine trends in CRC mortality from 1999-2012. Analyses examined the changing role of medical preventions and health behaviors in catalyzing SES and racial/ethnic inequalities in CRC mortality.RESULTS:Lower SES as well as Black, Hispanic, Asian/Pacific Islander, and Native American race/ethnicity were associated with decreased access to age-appropriate screening and/or increased prevalence of behavioral risk factors. Analyses further revealed that SES and racial/ethnic inequalities were partially determined by differences in engagement in two preventive factors: use of colonoscopy, and participation in physical activity.DISCUSSION:Social inequalities were not completely determined by behavioral risk factors. Nevertheless, a more equitable distribution of preventive medicines has the potential to reduce both the risk of, and social inequalities in, CRC mortality.