Coding of Childhood Psychiatric and Neurodevelopmental Disorders in Electronic Health Records of a Large Integrated Health Care System: Validation Study.

Background: Mental, emotional, and behavioral disorders are chronic pediatric conditions, and their prevalence has been on the rise over recent decades. Affected children have long-term health sequelae and a decline in health-related quality of life. Due to the lack of a validated database for pharmacoepidemiological research on selected mental, emotional, and behavioral disorders, there is uncertainty in their reported prevalence in the literature. objectives: We aimed to evaluate the accuracy of coding related to pediatric mental, emotional, and behavioral disorders in a large integrated health care system's electronic health records (EHRs) and compare the coding quality before and after the implementation of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding as well as before and after the COVID-19 pandemic. Methods: Medical records of 1200 member children aged 2-17 years with at least 1 clinical visit before the COVID-19 pandemic (January 1, 2012, to December 31, 2014, the ICD-9-CM coding period; and January 1, 2017, to December 31, 2019, the ICD-10-CM coding period) and after the COVID-19 pandemic (January 1, 2021, to December 31, 2022) were selected with stratified random sampling from EHRs for chart review. Two trained research associates reviewed the EHRs for all potential cases of autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), major depression disorder (MDD), anxiety disorder (AD), and disruptive behavior disorders (DBD) in children during the study period. Children were considered cases only if there was a mention of any one of the conditions (yes for diagnosis) in the electronic chart during the corresponding time period. The validity of diagnosis codes was evaluated by directly comparing them with the gold standard of chart abstraction using sensitivity, specificity, positive predictive value, negative predictive value, the summary statistics of the F-score, and Youden J statistic. κ statistic for interrater reliability among the 2 abstractors was calculated. Results: The overall agreement between the identification of mental, behavioral, and emotional conditions using diagnosis codes compared to medical record abstraction was strong and similar across the ICD-9-CM and ICD-10-CM coding periods as well as during the prepandemic and pandemic time periods. The performance of AD coding, while strong, was relatively lower compared to the other conditions. The weighted sensitivity, specificity, positive predictive value, and negative predictive value for each of the 5 conditions were as follows: 100%, 100%, 99.2%, and 100%, respectively, for ASD; 100%, 99.9%, 99.2%, and 100%, respectively, for ADHD; 100%, 100%, 100%, and 100%, respectively for DBD; 87.7%, 100%, 100%, and 99.2%, respectively, for AD; and 100%, 100%, 99.2%, and 100%, respectively, for MDD. The F-score and Youden J statistic ranged between 87.7% and 100%. The overall agreement between abstractors was almost perfect (κ=95%). Conclusions: Diagnostic codes are quite reliable for identifying selected childhood mental, behavioral, and emotional conditions. The findings remained similar during the pandemic and after the implementation of the ICD-10-CM coding in the EHR system.

Management, Utilization, and Outcomes of Preterm Labor in an Integrated Health Care System.

OBJECTIVE: Fetal fibronectin (fFN) testing and transvaginal ultrasound (TVUS) are diagnostic tools used to predict impending spontaneous preterm birth (sPTB) among women presenting with preterm labor (PTL). We evaluated the association between fFN testing or TVUS cervical length (CL) measurement in predicting sPTB, respiratory distress syndrome (RDS), neonatal intensive care unit (NICU) admission, and sPTB-related costs. STUDY DESIGN: We conducted a retrospective cohort study using data from the Kaiser Permanente Southern California electronic health system (January 1, 2009-December 31, 2020) using diagnostic and procedure codes, along with a natural language processing algorithm to identify pregnancies with PTL evaluations. PTL evaluation was defined as having fFN and/or TVUS assessment. Outcomes were ascertained using diagnostic, procedural, and diagnosis-related group codes. Multivariable logistic regression assessed the association between fFN and/or TVUS results and perinatal outcomes. RESULTS: Compared with those without PTL evaluations, those with positive fFN tests had higher adjusted odds ratio (adj.OR) for sPTB (2.95, 95% confidence interval [CI]: 2.64, 3.29), RDS (2.34, 95% CI: 2.03, 2.69), and NICU admission (2.24, 95% CI: 2.01, 2.50). In contrast, those who tested negative had lower odds for sPTB (adj.OR: 0.75, 95% CI: 0.70, 0.79), RDS (adj.OR: 0.67, 95% CI: 0.61, 0.73), and NICU admission (adj.OR: 0.74, 95% CI: 0.70, 0.79). Among those with positive fFN results, the odds of sPTB was inversely associated with CL. Health care costs for mothers and neonates were lowest for those with fFN testing only. CONCLUSION: This study demonstrates that positive fFN results were associated with an increased odds of sPTB, RDS, and NICU admission and the association with sPTB was inversely proportional to CL. Additionally, negative fFN results were associated with decreased odds of sPTB, RDS, and NICU admissions. fFN testing may predict these and other sPTB-related adverse outcomes hence its utility should be explored further. Moreover, fFN testing has some cost savings over TVUS. KEY POINTS: · Patients with positive fFN tests had higher odds of sPTB, RDS, and NICU admission.. · Inverse relationship between sPTB and CL among those with positive fFN tests was observed.. · Health care costs for mothers and neonates were lowest for those with fFN testing only..

Association between particulate air pollution and hypertensive disorders in pregnancy: A retrospective cohort study.

BACKGROUND: Epidemiological findings regarding the association of particulate matter ≤2.5 µm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy. METHODS AND FINDINGS: A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly PM2.5 exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 µg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochran's Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP. CONCLUSIONS: Our findings add to the literature on associations between air pollution exposure and HDP. To our knowledge, this is the first study reporting that specific air pollution components, mixture effects, and susceptible windows of PM2.5 may affect GH and PE-E differently.

Association of Antepartum and Postpartum Air Pollution Exposure With Postpartum Depression in Southern California.

Importance: Women are especially vulnerable to mental health matters post partum because of biological, emotional, and social changes during this period. However, epidemiologic evidence of an association between air pollution exposure and postpartum depression (PPD) is limited. Objective: To examine the associations between antepartum and postpartum maternal air pollution exposure and PPD. Design, Setting, and Participants: This retrospective cohort study used data from Kaiser Permanente Southern California (KPSC) electronic health records and included women who had singleton live births at KPSC facilities between January 1, 2008, and December 31, 2016. Data were analyzed between January 1 and May 10, 2023. Exposures: Ambient air pollution exposures were assessed based on maternal residential addresses using monthly averages of particulate matter less than or equal to 2.5 µm (PM2.5), particulate matter less than or equal to 10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) from spatial interpolation of monitoring station measurements. Constituents of PM2.5 (sulfate, nitrate, ammonium, organic matter, and black carbon) were obtained from fine-resolution geoscience-derived models based on satellite, ground-based monitor, and chemical transport modeling data. Main Outcomes and Measures: Participants with an Edinburgh Postnatal Depression Scale score of 10 or higher during the 6 months after giving birth were referred to a clinical interview for further assessment and diagnosis. Ascertainment of PPD was defined using a combination of diagnostic codes and prescription medications. Results: The study included 340 679 participants (mean [SD] age, 30.05 [5.81] years), with 25 674 having PPD (7.54%). Increased risks for PPD were observed to be associated with per-IQR increases in antepartum and postpartum exposures to O3 (adjusted odds ratio [AOR], 1.09; 95% CI, 1.06-1.12), PM10 (AOR, 1.02; 95% CI, 1.00-1.04), and PM2.5 (AOR, 1.02; 95% CI, 1. 00-1.03) but not with NO2; PPD risks were mainly associated with PM2.5 organic matter and black carbon. Overall, a higher risk of PPD was associated with O3 during the entire pregnancy and postpartum periods and with PM exposure during the late pregnancy and postpartum periods. Conclusions and Relevance: The study findings suggest that long-term exposure to antepartum and postpartum air pollution was associated with higher PPD risks. Identifying the modifiable environmental risk factors and developing interventions are important public health issues to improve maternal mental health and alleviate the disease burden of PPD.

Analysis of Heat Exposure During Pregnancy and Severe Maternal Morbidity.

Importance: The rate of severe maternal morbidity (SMM) is continuously increasing in the US. Evidence regarding the associations of climate-related exposure, such as environmental heat, with SMM is lacking. Objective: To examine associations between long- and short-term maternal heat exposure and SMM. Design, Setting, and Participants: This retrospective population-based epidemiological cohort study took place at a large integrated health care organization, Kaiser Permanente Southern California, between January 1, 2008, and December 31, 2018. Data were analyzed from February to April 2023. Singleton pregnancies with data on SMM diagnosis status were included. Exposures: Moderate, high, and extreme heat days, defined as daily maximum temperatures exceeding the 75th, 90th, and 95th percentiles of the time series data from May through September 2007 to 2018 in Southern California, respectively. Long-term exposures were measured by the proportions of different heat days during pregnancy and by trimester. Short-term exposures were represented by binary variables of heatwaves with 9 different definitions (combining percentile thresholds with 3 durations; ie, ≥2, ≥3, and ≥4 consecutive days) during the last gestational week. Main Outcomes and Measures: The primary outcome was SMM during delivery hospitalization, measured by 20 subconditions excluding blood transfusion. Discrete-time logistic regression was used to estimate associations with long- and short-term heat exposure. Effect modification by maternal characteristics and green space exposure was examined using interaction terms. Results: There were 3446 SMM cases (0.9%) among 403 602 pregnancies (mean [SD] age, 30.3 [5.7] years). Significant associations were observed with long-term heat exposure during pregnancy and during the third trimester. High exposure (≥80th percentile of the proportions) to extreme heat days during pregnancy and during the third trimester were associated with a 27% (95% CI, 17%-37%; P < .001) and 28% (95% CI, 17%-41%; P < .001) increase in risk of SMM, respectively. Elevated SMM risks were significantly associated with short-term heatwave exposure under all heatwave definitions. The magnitude of associations generally increased from the least severe (HWD1: daily maximum temperature >75th percentile lasting for ≥2 days; odds ratio [OR], 1.32; 95% CI, 1.17-1.48; P < .001) to the most severe heatwave exposure (HWD9: daily maximum temperature >95th percentile lasting for ≥4 days; OR, 2.39; 95% CI, 1.62-3.54; P < .001). Greater associations were observed among mothers with lower educational attainment (OR for high exposure to extreme heat days during pregnancy, 1.43; 95% CI, 1.26-1.63; P < .001) or whose pregnancies started in the cold season (November through April; OR, 1.37; 95% CI, 1.24-1.53; P < .001). Conclusions and Relevance: In this retrospective cohort study, long- and short-term heat exposure during pregnancy was associated with higher risk of SMM. These results might have important implications for SMM prevention, particularly in a changing climate.

Maternal exposure to ambient air pollution mixture and premature rupture of membranes: Evidence from a large cohort in Southern California (2008-2018).

BACKGROUND: There is minimal evidence of relationships between maternal air pollution exposure and spontaneous premature rupture of membranes (SPROM), a critical obstetrical problem that can significantly increase maternal and fetal mortality and morbidity. No prior study has explored the PROM risk related to specific components of particulate matter with aerodynamic diameters of ≤ 2.5 µm (PM2.5). We examined associations between maternal exposure to nitrogen dioxide (NO2), ozone (O3), PM2.5, PM10, and PM2.5 constituents and SPROM. METHODS: A large retrospective cohort study was conducted and included 427,870 singleton live births from Kaiser Permanente Southern California during 2008-2018. Monthly averages of NO2, O3 (8-h daily maximum), PM2.5, and PM10 were measured using empirical Bayesian kriging based on measurements from monitoring stations. Data on PM2.5 sulfate, nitrate, ammonium, organic matter, and black carbon were obtained from a fine-resolution model. A discrete time approach with pooled logistic regressions was used to estimate associations throughout the pregnancy and based on trimesters and gestational months. The quantile-based g-computation models were fitted to examine the effects of 1) the air pollution mixture of four pollutants of interest and 2) the mixture of PM2.5 components. RESULTS: There were 37,857 SPROM cases (8.8%) in our study population. We observed relationships between SPROM and maternal exposure to NO2, O3, and PM2.5. PM2.5 sulfate, nitrate, ammonium, and organic matter were associated with higher SPROM risks in the single-pollutant model. Mixture analyses demonstrated that the overall effects of the air pollution mixture and PM2.5 mixture in this study were mainly driven by O3 and PM2.5 nitrate, respectively. Underweight mothers had a significantly higher risk of SPROM associated with NO2. CONCLUSION: Our findings add to the literature on associations between air pollution exposure and SPROM. This is the first study reporting the impact of PM2.5 constituents on SPROM.

Examining the Relationship Between Extreme Temperature, Microclimate Indicators, and Gestational Diabetes Mellitus in Pregnant Women Living in Southern California.

Few studies have assessed extreme temperatures' impact on gestational diabetes mellitus (GDM). We examined the relation between GDM risk with weekly exposure to extreme high and low temperatures during the first 24 weeks of gestation and assessed potential effect modification by microclimate indicators. Methods: We utilized 2008-2018 data for pregnant women from Kaiser Permanente Southern California electronic health records. GDM screening occurred between 24 and 28 gestational weeks for most women using the Carpenter-Coustan criteria or the International Association of Diabetes and Pregnancy Study Groups criteria. Daily maximum, minimum, and mean temperature data were linked to participants' residential address. We utilized distributed lag models, which assessed the lag from the first to the corresponding week, with logistic regression models to examine the exposure-lag-response associations between the 12 weekly extreme temperature exposures and GDM risk. We used the relative risk due to interaction (RERI) to estimate the additive modification of microclimate indicators on the relation between extreme temperature and GDM risk. Results: GDM risks increased with extreme low temperature during gestational weeks 20--24 and with extreme high temperature at weeks 11-16. Microclimate indicators modified the influence of extreme temperatures on GDM risk. For example, there were positive RERIs for high-temperature extremes and less greenness, and a negative RERI for low-temperature extremes and increased impervious surface percentage. Discussion: Susceptibility windows to extreme temperatures during pregnancy were observed. Modifiable microclimate indicators were identified that may attenuate temperature exposures during these windows, which could in turn reduce the health burden from GDM.

Modeling spatially varying compliance effects of PM2.5 exposure reductions on gestational diabetes mellitus in southern California: Results from electronic health record data of a large pregnancy cohort.

Gestational diabetes mellitus (GDM) is a major pregnancy complication affecting approximately 14.0% of pregnancies around the world. Air pollution exposure, particularly exposure to PM2.5, has become a major environmental issue affecting health, especially for vulnerable pregnant women. Associations between PM2.5 exposure and adverse birth outcomes are generally assumed to be the same throughout a large geographical area. However, the effects of air pollution on health can very spatially in subpopulations. Such spatially varying effects are likely due to a wide range of contextual neighborhood and individual factors that are spatially correlated, including SES, demographics, exposure to housing characteristics and due to different composition of particulate matter from different emission sources. This combination of elevated environmental hazards in conjunction with socioeconomic-based disparities forms what has been described as a "double jeopardy" for marginalized sub-populations. In this manuscript our analysis combines both an examination of spatially varying effects of a) unit-changes in exposure and examines effects of b) changes from current exposure levels down to a fixed compliance level, where compliance levels correspond to the Air Quality Standards (AQS) set by the U.S. Environmental Protection Agency (EPA) and World Health Organization (WHO) air quality guideline values. Results suggest that exposure reduction policies should target certain "hotspot" areas where size and effects of potential reductions will reap the greatest rewards in terms of health benefits, such as areas of southeast Los Angeles County which experiences high levels of PM2.5 exposures and consist of individuals who may be particularly vulnerable to the effects of air pollution on the risk of GDM.

Association between urban green space and postpartum depression, and the role of physical activity: a retrospective cohort study in Southern California.

Background: Little research exists regarding the relationships between green space and postpartum depression (PPD). We aimed to investigate the relationships between PPD and green space exposure, and the mediating role of physical activity (PA). Methods: Clinical data were obtained from Kaiser Permanente Southern California electronic health records in 2008-2018. PPD ascertainment was based on both diagnostic codes and prescription medications. Maternal residential green space exposures were assessed using street view-based measures and vegetation types (i.e., street tree, low-lying vegetation, and grass), satellite-based measures [i.e., Normalized Difference Vegetation Index (NDVI), land-cover green space, and tree canopy cover], and proximity to the nearest park. Multilevel logistic regression was applied to estimate the association between green space and PPD. A causal mediation analysis was performed to estimate the proportion mediated by PA during pregnancy in the total effects of green space on PPD. Findings: In total, we included 415,020 participants (30.2 ± 5.8 years) with 43,399 (10.5%) PPD cases. Hispanic mothers accounted for about half of the total population. A reduced risk for PPD was associated with total green space exposure based on street-view measure [500 m buffer, adjusted odds ratio (OR) per interquartile range: 0.98, 95% CI: 0.97-0.99], but not NDVI, land-cover greenness, or proximity to a park. Compared to other types of green space, tree coverage showed stronger protective effects (500 m buffer, OR = 0.98, 95% CI: 0.97-0.99). The proportions of mediation effects attributable to PA during pregnancy ranged from 2.7% to 7.2% across green space indicators. Interpretation: Street view-based green space and tree coverage were associated with a decreased risk of PPD. The observed association was primarily due to increased tree coverage, rather than low-lying vegetation or grass. Increased PA was a plausible pathway linking green space to lower risk for PPD. Funding: National Institute of Environmental Health Sciences (NIEHS; R01ES030353).

Identification of Postpartum Depression in Electronic Health Records: Validation in a Large Integrated Health Care System.

BACKGROUND: The accuracy of electronic health records (EHRs) for identifying postpartum depression (PPD) is not well studied. OBJECTIVE: This study aims to evaluate the accuracy of PPD reporting in EHRs and compare the quality of PPD data collected before and after the implementation of the International Classification of Diseases, Tenth Revision (ICD-10) coding in the health care system. METHODS: Information on PPD was extracted from a random sample of 400 eligible Kaiser Permanente Southern California patients' EHRs. Clinical diagnosis codes and pharmacy records were abstracted for two time periods: January 1, 2012, through December 31, 2014 (International Classification of Diseases, Ninth Revision [ICD-9] period), and January 1, 2017, through December 31, 2019 (ICD-10 period). Manual chart reviews of clinical records for PPD were considered the gold standard and were compared with corresponding electronically coded diagnosis and pharmacy records using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Kappa statistic was calculated to measure agreement. RESULTS: Overall agreement between the identification of depression using combined diagnosis codes and pharmacy records with that of medical record review was strong (κ=0.85, sensitivity 98.3%, specificity 83.3%, PPV 93.7%, NPV 95.0%). Using only diagnosis codes resulted in much lower sensitivity (65.4%) and NPV (50.5%) but good specificity (88.6%) and PPV (93.5%). Separately, examining agreement between chart review and electronic coding among diagnosis codes and pharmacy records showed sensitivity, specificity, and NPV higher with prescription use records than with clinical diagnosis coding for PPD, 96.5% versus 72.0%, 96.5% versus 65.0%, and 96.5% versus 65.0%, respectively. There was no notable difference in agreement between ICD-9 (overall κ=0.86) and ICD-10 (overall κ=0.83) coding periods. CONCLUSIONS: PPD is not reliably captured in the clinical diagnosis coding of EHRs. The accuracy of PPD identification can be improved by supplementing clinical diagnosis with pharmacy use records. The completeness of PPD data remained unchanged after the implementation of the ICD-10 diagnosis coding.

The role of extreme heat exposure on premature rupture of membranes in Southern California: A study from a large pregnancy cohort.

BACKGROUND: Significant mortality and morbidity in pregnant women and their offspring are linked to premature rupture of membranes (PROM). Epidemiological evidence for heat-related PROM risk is extremely limited. We investigated associations between acute heatwave exposure and spontaneous PROM. METHODS: We conducted this retrospective cohort study among mothers in Kaiser Permanente Southern California who experienced membrane ruptures during the warm season (May-September) from 2008 to 2018. Twelve definitions of heatwaves with different cut-off percentiles (75th, 90th, 95th, and 98th) and durations (≥ 2, 3, and 4 consecutive days) were developed using the daily maximum heat index, which incorporates both daily maximum temperature and minimum relative humidity in the last gestational week. Cox proportional hazards models were fitted separately for spontaneous PROM, term PROM (TPROM), and preterm PROM (PPROM) with zip codes as the random effect and gestational week as the temporal unit. Effect modification by air pollution (i.e., PM2.5 and NO2), climate adaptation measures (i.e., green space and air conditioning [AC] penetration), sociodemographic factors, and smoking behavior was examined. RESULTS: In total, we included 190,767 subjects with 16,490 (8.6%) spontaneous PROMs. We identified a 9-14% increase in PROM risks associated with less intense heatwaves. Similar patterns as PROM were found for TPROM and PPROM. The heat-related PROM risks were greater among mothers exposed to a higher level of PM2.5 during pregnancy, under 25 years old, with lower education and household income level, and who smoked. Even though climate adaptation factors were not statistically significant effect modifiers, mothers living with lower green space or lower AC penetration were at consistently higher heat-related PROM risks compared to their counterparts. CONCLUSION: Using a rich and high-quality clinical database, we detected harmful heat exposure for spontaneous PROM in preterm and term deliveries. Some subgroups with specific characteristics were more susceptible to heat-related PROM risk.

Examining recent trends in spontaneous and iatrogenic preterm birth across race and ethnicity in a large managed care population.

BACKGROUND: For the past several decades, epidemiological studies originating from the United States have consistently reported increasing rates of preterm birth (PTB). Despite the implementation of several clinical and public health interventions to reduce PTB rates, it remains the leading cause of infant morbidity and mortality in the United States and around the world. OBJECTIVE: This study aimed to examine recent trends in preterm birth and its clinical subtypes by maternal race and ethnicity among singleton births. STUDY DESIGN: Kaiser Permanente Southern California electronic health records for all singleton births between 2009 and 2020 (n=427,698) were used to examine preterm birth trends and their subtypes (spontaneous and iatrogenic preterm births). Data on preterm labor triage extracted from electronic health records using natural language processing were used to define preterm birth subtypes. Maternal race and ethnicity are categorized as non-Hispanic White, non-Hispanic Black, Hispanic, and non-Hispanic Asian or Pacific Islander. Multiple logistic regression was used to quantify the linear trend for preterm birth and its subtypes. Racial and ethnic trends were further examined by considering statistical interactions and stratifications. RESULTS: From 2009 to 2020, the overall preterm birth rate decreased by 9.12% (from 8.04% to 7.31%; P<.001). The rates decreased by 19.29% among non-Hispanic Whites (from 7.23% to 5.83%; P<.001), 6.15% among Hispanics (from 7.82% to 7.34%; P=.036), and 12.60% among non-Hispanic Asian or Pacific Islanders (from 8.90% to 7.78%; P<.001), whereas a nonsignificantly increased preterm birth rate (8.45%) was observed among non-Hispanic Blacks (from 9.91% to 10.75%; P=.103). Between 2009 and 2020, overall spontaneous preterm birth rates decreased by 28.85% (from 5.75% to 4.09%; P<.001). However, overall iatrogenic preterm birth rates increased by 40.45% (from 2.29% to 3.22%; p<.001). Spontaneous preterm birth rates decreased by 34.73% among non-Hispanic Whites (from 5.44% to 3.55%; P<.001), 19.75% among non-Hispanic Blacks (from 6.82% to 5.47%; P<.001), 22.96% among Hispanics (from 5.55% to 4.28%; P<.001), and 28.19% among non-Hispanic Asian or Pacific Islanders (from 6.50% to 4.67%; P<.001). Iatrogenic preterm birth rates increased by 52.42% among non-Hispanic Whites (from 1.88% to 2.61%; P<.001), 107.89% among non-Hispanic Blacks (from 3.18% to 6.13%; P<.001), 46.88% among Hispanics (from 2.29% to 3.26%; P<.001), and 42.21% among non-Hispanic Asian or Pacific Islanders (from 2.45% to 3.44%; P<.001). CONCLUSION: The overall preterm birth rate decreased over time and was driven by a decrease in the spontaneous preterm birth rate. There is racial and ethnic variability in the rates of spontaneous preterm birth and iatrogenic preterm birth. The observed increase in iatrogenic preterm birth among all racial and ethnic groups, especially non-Hispanic Blacks, is disconcerting and needs further investigation.

Postpartum Migraine Headache Coding in Electronic Health Records of a Large Integrated Health Care System: Validation Study.

BACKGROUND: Migraine is a common neurological disorder characterized by repeated headaches of varying intensity. The prevalence and severity of migraine headaches disproportionally affects women, particularly during the postpartum period. Moreover, migraines during pregnancy have been associated with adverse maternal outcomes, including preeclampsia and postpartum stroke. However, due to the lack of a validated instrument for uniform case ascertainment on postpartum migraine headache, there is uncertainty in the reported prevalence in the literature. OBJECTIVE: The aim of this study was to evaluate the completeness and accuracy of reporting postpartum migraine headache coding in a large integrated health care system's electronic health records (EHRs) and to compare the coding quality before and after the implementation of the International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) codes and pharmacy records in EHRs. METHODS: Medical records of 200 deliveries in all 15 Kaiser Permanente Southern California hospitals during 2 time periods, that is, January 1, 2012 through December 31, 2014 (International Classification of Diseases, 9th revision, Clinical Modification [ICD-9-CM] coding period) and January 1, 2017 through December 31, 2019 (ICD-10-CM coding period), were randomly selected from EHRs for chart review. Two trained research associates reviewed the EHRs for all 200 women for postpartum migraine headache cases documented within 1 year after delivery. Women were considered to have postpartum migraine headache if either a mention of migraine headache (yes for diagnosis) or a prescription for treatment of migraine headache (yes for pharmacy records) was noted in the electronic chart. Results from the chart abstraction served as the gold standard and were compared with corresponding diagnosis and pharmacy prescription utilization records for both ICD-9-CM and ICD-10-CM coding periods through comparisons of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), as well as the summary statistics of F-score and Youden J statistic (J). The kappa statistic (κ) for interrater reliability was calculated. RESULTS: The overall agreement between the identification of migraine headache using diagnosis codes and pharmacy records compared to the medical record review was strong. Diagnosis coding (F-score=87.8%; J=82.5%) did better than pharmacy records (F-score=72.7%; J=57.5%) when identifying cases, but combining both of these sources of data produced much greater accuracy in the identification of postpartum migraine cases (F-score=96.9%; J=99.7%) with sensitivity, specificity, PPV, and NPV of 100%, 99.7%, 93.9%, and 100%, respectively. Results were similar across the ICD-9-CM (F-score=98.7%, J=99.9%) and ICD-10-CM coding periods (F-score=94.9%; J=99.6%). The interrater reliability between the 2 research associates for postpartum migraine headache was 100%. CONCLUSIONS: Neither diagnostic codes nor pharmacy records alone are sufficient for identifying postpartum migraine cases reliably, but when used together, they are quite reliable. The completeness of the data remained similar after the implementation of the ICD-10-CM coding in the EHR system.

Identification of Preterm Labor Evaluation Visits and Extraction of Cervical Length Measures from Electronic Health Records Within a Large Integrated Health Care System: Algorithm Development and Validation.

BACKGROUND: Preterm birth (PTB) represents a significant public health problem in the United States and throughout the world. Accurate identification of preterm labor (PTL) evaluation visits is the first step in conducting PTB-related research. OBJECTIVE: We aimed to develop a validated computerized algorithm to identify PTL evaluation visits and extract cervical length (CL) measures from electronic health records (EHRs) within a large integrated health care system. METHODS: We used data extracted from the EHRs at Kaiser Permanente Southern California between 2009 and 2020. First, we identified triage and hospital encounters with fetal fibronectin (fFN) tests, transvaginal ultrasound (TVUS) procedures, PTL medications, or PTL diagnosis codes within 240/7-346/7 gestational weeks. Second, clinical notes associated with triage and hospital encounters within 240/7-346/7 gestational weeks were extracted from EHRs. A computerized algorithm and an automated process were developed and refined by multiple iterations of chart review and adjudication to search the following PTL indicators: fFN tests, TVUS procedures, abdominal pain, uterine contractions, PTL medications, and descriptions of PTL evaluations. An additional process was constructed to extract the CLs from the corresponding clinical notes of these identified PTL evaluation visits. RESULTS: A total of 441,673 live birth pregnancies were identified between 2009 and 2020. Of these, 103,139 pregnancies (23.35%) had documented PTL evaluation visits identified by the computerized algorithm. The trend of pregnancies with PTL evaluation visits slightly decreased from 24.41% (2009) to 17.42% (2020). Of the first 103,139 PTL visits, 19,439 (18.85%) and 44,423 (43.97%) had an fFN test and a TVUS, respectively. The percentage of first PTL visits with an fFN test decreased from 18.06% at 240/7 gestational weeks to 2.32% at 346/7 gestational weeks, and TVUS from 54.67% at 240/7 gestational weeks to 12.05% in 346/7 gestational weeks. The mean (SD) of the CL was 3.66 (0.99) cm with a mean range of 3.61-3.69 cm that remained stable across the study period. Of the pregnancies with PTL evaluation visits, the rate of PTB remained stable over time (20,399, 19.78%). Validation of the computerized algorithms against 100 randomly selected records from these potential PTL visits showed positive predictive values of 97%, 94.44%, 100%, and 96.43% for the PTL evaluation visits, fFN tests, TVUS, and CL, respectively, along with sensitivity values of 100%, 90%, and 90%, and specificity values of 98.8%, 100%, and 98.6% for the fFN test, TVUS, and CL, respectively. CONCLUSIONS: The developed computerized algorithm effectively identified PTL evaluation visits and extracted the corresponding CL measures from the EHRs. Validation against this algorithm achieved a high level of accuracy. This computerized algorithm can be used for conducting PTL- or PTB-related pharmacoepidemiologic studies and patient care reviews.

Exposure to air pollutant mixture and gestational diabetes mellitus in Southern California: Results from electronic health record data of a large pregnancy cohort.

BACKGROUND: Epidemiological findings are inconsistent regarding the associations between air pollution exposure during pregnancy and gestational diabetes mellitus (GDM). Several limitations exist in previous studies, including potential outcome and exposure misclassification, unassessed confounding, and lack of simultaneous consideration of air pollution mixtures and particulate matter (PM) constituents. OBJECTIVES: To assess the association between GDM and maternal residential exposure to air pollution, and the joint effect of the mixture of air pollutants and PM constituents. METHODS: Detailed clinical data were obtained for 395,927 pregnancies in southern California (2008-2018) from Kaiser Permanente Southern California (KPSC) electronic health records. GDM diagnosis was based on KPSC laboratory tests. Monthly average concentrations of fine particulate matter < 2.5 µm (PM2.5), <10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated using kriging interpolation of Environmental Protection Agency's routine monitoring station data, while PM2.5 constituents (i.e., sulfate, nitrate, ammonium, organic matter and black carbon) were estimated using a fine-resolution geoscience-derived model. A multilevel logistic regression was used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of air pollution and PM component mixtures. Main analyses adjusted for maternal age, race/ethnicity, education, median family household income, pre-pregnancy BMI, smoking during pregnancy, insurance type, season of conception and year of delivery. RESULTS: The incidence of GDM was 10.9% in the study population. In single-pollutant models, we observed an increased odds for GDM associated with exposures to PM2.5, PM10, NO2 and PM2.5 constituents. The association was strongest for NO2 [adjusted odds ratio (OR) per interquartile range: 1.176, 95% confidence interval (CI): 1.147-1.205)]. In multi-pollutant models, increased ORs for GDM in association with one quartile increase in air pollution mixtures were found for both kriging-based regional air pollutants (NO2, PM2.5, and PM10, OR = 1.095, 95% CI: 1.082-1.108) and PM2.5 constituents (i.e., sulfate, nitrate, ammonium, organic matter and black carbon, OR = 1.258, 95% CI: 1.206-1.314); NO2 (78%) and black carbon (48%) contributed the most to the overall mixture effects among all krigged air pollutants and all PM2.5 constituents, respectively. The risk of GDM associated with air pollution exposure were significantly higher among Hispanic mothers, and overweight/obese mothers. CONCLUSION: This study found that exposure to a mixture of ambient PM2.5, PM10, NO2, and PM2.5 chemical constituents was associated with an increased risk of GDM. NO2 and black carbon PM2.5 contributed most to GDM risk.

Insomnia and Susceptibility to Depressive Symptoms and Fatigue in Diverse Breast Cancer Survivors.

Background: Nearly 40% of breast cancer survivors have insomnia, yet, information how this condition affects their quality of life is lacking. We examined the association between insomnia and depressive symptoms and fatigue in breast cancer survivors. Methods: Participants were recruited from a community health plan. We conducted a cross-sectional analysis to examine the association between current insomnia (using Insomnia Severity Index [ISI]) and current depressive symptoms (using Inventory of Depressive Symptomology [IDS]) and fatigue (using Fatigue Symptom Inventory [FSI]) in 315 breast cancer survivors who did not have major depressive disorder. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression. Results: The cohort included 30% minority women whose median time since breast cancer diagnosis was 6 years. Survivors with current insomnia symptoms (ISI ≥8) had a sixfold greater odds of current depressive symptoms (IDS >14, OR = 5.98, 95% CI: 3.04-11.76), after adjusting for lifetime insomnia history (OR = 2.01, 95% CI: 1.03-3.94) and perceived stress (OR = 6.37, 95% CI: 2.48-16.32). Insomnia symptoms were markedly associated with moderate fatigue (FSI >3, OR = 5.02, 95% CI: 2.66-9.44). Ever use of antidepressants or sleep medications post-breast cancer diagnosis was not associated with lower odds of current depressive symptoms or feeling fatigued in those with insomnia symptoms. Conclusion: Current insomnia symptoms were strongly correlated with current depressive symptoms and fatigue. Survivorship care plans should consider incorporating insomnia screening to that may potentially enhance quality of life domains.

Medication adherence, molecular monitoring, and clinical outcomes in patients with chronic myelogenous leukemia in a large HMO.

OBJECTIVE: Our objective was to examine the association between adherence to tyrosine kinase inhibitors (TKIs) and molecular monitoring and the risk of disease progression or mortality among patients with chronic phase chronic myeloid leukemia (CML). DESIGN: We assembled a retrospective cohort of patients with CML (chronic phase, no prior cancer history, and confirmed to be Philadelphia chromosome positive) using data from electronic health records and chart reviews. Medication possession ratio (MPR) was used to measure drug adherence. SETTING: A large, community-based, integrated health plan in Southern California. PARTICIPANTS: The cohort consisted of 245 adult patients (≥18 years old) with Philadelphia positive chronic phase CML diagnosed from 2001 to 2012 and followed through 2013. MAIN OUTCOME MEASURES: In survival analyses, we examined the association of TKI adherence (MPR) and polymerase chain reaction (PCR) monitoring test frequency with the composite clinical outcome, progression to accelerated phase disease-blast crisis or mortality (progression-free survival). The cohort was followed for a maximum of 13 years (median 4.6 years). RESULTS: Over 90% of the cohort initiated TKI therapy within 3 months of diagnosis, and the mean MPR was 88% (SD 18%). Virtually all patients (96%) started on imatinib. The rates of progression to accelerated phase-blast crisis and mortality were lower in patients with greater TKI adherence (20.4/1000 person-years) versus lower adherence (27.0/1000 person-years). Patients who underwent PCR monitoring had a significantly reduced risk of progression or mortality, which was seen in patients with high and low TKI adherence status from both the groups (hazard ratio [HR] 0.07 [95% CI 0.03-0.19 if MPR >90%] and HR 0.70 [95% CI 0.02-0.21 if MPR<90%]). CONCLUSION: Our results suggest that close clinical monitoring, which includes PCR monitoring in patients with high and low TKI drug adherence, is associated with a lower risk of progression or mortality.

Cardiovascular Disease After Aromatase Inhibitor Use.

IMPORTANCE: Cardiovascular disease (CVD) is an important cause of death in older patients with breast cancer. However, limited information exists on the long-term effect of aromatase inhibitor (AI) use on CVD risk in breast cancer survivors. To this point, no other population-based studies have been able to adjust for CVD risk factors or cardiovascular medications. OBJECTIVE: To determine the long-term influence of adjuvant endocrine therapies on CVD in a cohort of postmenopausal breast cancer survivors in analyses that accounted for major CVD risk factors, medication use, chemotherapy, and radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort of postmenopausal women with breast cancer diagnosed from January 1, 1991, to December 31, 2010, and followed up through December 31, 2011 (maximum, 21 years [72 886 person-years]), was evaluated using records from a managed care organization with nearly 20 community hospitals in California. A total of 13 273 postmenopausal women with hormone receptor-positive breast cancer without prior CVD were included. Cardiovascular disease incidence was compared across endocrine therapy categories. Information on demographics, comorbidity, medication, use, and CVD risk was captured from electronic health records. Multivariate Cox proportional hazards models using time-dependent endocrine drug use variables and propensity scores were conducted. Data analysis was conducted from September 15, 2014, to February 1, 2016. EXPOSURES: Women were grouped by endocrine therapy status (tamoxifen citrate only, AI only, both, or neither). MAIN OUTCOMES AND MEASURES: Person-year rates of CVD for each therapy group. RESULTS: During 72 886 person-years in 13 273 women (mean [SD] age, 66.8 [8.1] years) with follow-up through 2011, we observed 3711 CVD events. In multivariable analyses (reported as hazard ratio [95% CI]), AI-only users had a similar risk of cardiac ischemia (myocardial infarction and angina) (adjusted, 0.97 [0.78-1.22]) and stroke (adjusted, 0.97 [0.70-1.33]) as tamoxifen-only users (reference). However, we found an increased risk of other CVD (dysrhythmia, valvular dysfunction, and pericarditis) (adjusted, 1.29 [1.11-1.50]) in women who used AIs only or sequentially after tamoxifen (1.26 [1.09-1.45]) vs tamoxifen (reference) as well nonhormone users (1.18 [1.02-1.35]). CONCLUSIONS AND RELEVANCE: The risk of the most serious cardiovascular events (cardiac ischemia or stroke) was not elevated in AI-only users compared with tamoxifen users. The finding that other CVD events combined were greater in AI users requires further study.

Effectiveness of bisphosphonate use and risk of contralateral breast cancer and recurrence in women with early-stage breast cancer treated with tamoxifen.

The effectiveness of bisphosphonates (BP) in reducing risk of second breast cancer and recurrence in observational studies has been minimally studied. We examined the association of oral BP use on risk of contralateral breast cancer (CBC) and recurrence in 16,781 women diagnosed with early-stage breast cancer from 1996 to 2007, treated with tamoxifen, and followed through December 31, 2009 at Kaiser Permanente Northern California (KPNC, n = 8857) and Southern California (KPSC, n = 7924). Sociodemographic, clinical, and pharmacy information were extracted from electronic medical records and cancer registries. CBC was identified from cancer registries, and recurrences from electronic health records and chart reviews. Multivariate Cox regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) treating BP use and hormonal therapy as time-varying variables. After mean 6.4 years of follow-up, 494 (3.0 %) women developed CBC. BP use post-breast cancer diagnosis (>93 % alendronate) ranged from 14.5 to 24.9 % at both study sites. Overall, there was no association of BP use with reduced risk of CBC (ever use, HR = 0.96; 95 % CI 0.67-1.38 and continuous use, HR = 1.03; 95 % CI 0.88, 1.20). Similar null associations were observed for recurrence (ever use, HR = 0.98; 95 % CI 0.82, 1.17 and continuous use, HR = 1.00; 95 % CI 0.92, 1.09). Associations varied somewhat by site yet confidence intervals overlapped. BP use was not associated with reduced risk of recurrence or new primary disease among women diagnosed with early breast cancer and treated with tamoxifen.