Identifying Elective Induction of Labor Among a Diverse Pregnant Population from Electronic Health Records within a Large Integrated Healthcare System.

OBJECTIVE: Distinguishing between medically indicated induction of labor (iIOL) and elective induction of labor (eIOL) is a daunting process for researchers. We aimed to develop a Natural Language Processing (NLP) algorithm to identify eIOLs from electronic health records (EHR) within a large integrated healthcare system. STUDY DESIGN: We used structured and unstructured data from Kaiser Permanente Southern California's EHR of patients who were <35 years old and had singleton deliveries between 37 and 40 gestational weeks. Induction of labor (IOL) pregnancies were identified if there was evidence of an IOL diagnosis code, procedure code, or documentation in a delivery flowsheet or progress note. A comprehensive NLP algorithm was developed and refined through an iterative process of chart reviews and adjudications, where IOL-associated reasons (medically indicated versus elective induction) were reviewed. The final algorithm was applied to discern the indications of IOLs performed during the study period. RESULTS: A total of 332,163 eligible pregnancies were identified between 01/01/2008-12/31/2022. Of these eligible pregnancies, 68,541 (20.6%) were IOL, of which 6,824 (10.0%) were eIOL. Validation of the NLP process against 300 randomly selected pregnancies (100 eIOL, iIOL, and non-IOL cases each) yielded a positive predictive value of 83.0% and 88.0% for eIOL and iIOL, respectively. The rates of eIOL among the maternal age groups ranged between 9.6% -10.3%, except for the < 20 years group (12.2%). Non-Hispanic White individuals had the highest rate of eIOL (13.2%), while non-Hispanic Asian/Pacific Islanders had the lowest rate of eIOL (7.8%). The rate of eIOL increased from 1.0% in the 37 weeks gestational age group to 20.6% the 40 weeks gestational age group. CONCLUSION: Findings suggest that the developed NLP algorithm effectively identifies eIOL. It can be utilized to support eIOL-related pharmaco-epidemiological studies, filling in knowledge gaps and providing content more relevant to researchers.

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 between SARS-CoV-2 Infection and Adverse Perinatal Outcomes by Race/Ethnicity in a Large Integrated Health Care System.

OBJECTIVE: Recent studies have reported associations between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy and adverse perinatal outcomes but the extent to which these associations vary by race/ethnicity remains uncertain. Therefore, we examined how the association between prenatal SARS-CoV-2 infection and adverse perinatal outcomes may be modified by race/ethnicity. STUDY DESIGN: A retrospective cohort study was performed using data on 67,986 pregnant women extracted from the Kaiser Permanente Southern California electronic health records between April 6, 2020, and December 31, 2021. Upon admission to labor and delivery, all women were routinely tested for coronavirus disease 2019 (COVID-19) using real-time reverse-transcriptase polymerase chain reaction test. Adjusted odds ratios (aORs) were used to estimate associations. RESULTS: During the study period, COVID-19 was diagnosed in 4,960 (7%) of singleton pregnancies, with the highest rates observed among Hispanics (9.4%) and non-Hispanic Blacks (6.2%). Compared with non-Hispanic Whites, Hispanics (aOR: 1.12, 95% CI: 1.03, 1.21) with SARS-CoV-2 infection had the highest odds of a pregnancy associated with nonreassuring fetal heart rate tracing. Neonates of all races/ethnicities, except for non-Hispanic Blacks, showed significantly increased odds of SARS-CoV-2 infection, with the highest risk observed among Asians/Pacific Islanders (aOR: 10.88, 95% CI: 1.33, 89.04). Non-Hispanic White mothers who tested positive were admitted to intensive care unit (ICU) at a higher rate at delivery and within 7 days of delivery (aOR: 34.77, 95% CI: 11.3, 107.04; aOR: 26.48, 95% CI: 9.55, 73.46, respectively). Hispanics were also at a significantly higher odds of admission to ICU (aOR: 4.62, 95% CI: 2.69, 7.94; aOR: 4.42, 95% CI: 2.58, 7.56, respectively). Non-Hispanic Black, Hispanic, and Asian/Pacific Islander mothers who tested positive for SARS-CoV-2 prenatally, were at increased risk for preeclampsia/eclampsia, and preterm birth as compared to non-Hispanic White mothers. CONCLUSION: The findings highlight racial/ethnic disparities in the association between SARS-CoV-2 infection and adverse perinatal outcomes. The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders. We also observed a remarkably high risk of ICU admission for non-Hispanic White mothers infected with SARS-CoV-2. KEY POINTS: · Race/ethnicity influences perinatal outcomes in pregnancies impacted by SARS-CoV-2.. · The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders.. · White mothers had a notably high risk of ICU admission at delivery following SARS-CoV-2 infection..

Rising Trends of Childhood Attention-Deficit/Hyperactivity Disorder in a Large Integrated Healthcare Delivery System in Southern California, 2010-2021.

OBJECTIVE: To evaluate trends of attention-deficit/hyperactivity disorder (ADHD) diagnosis rates among children aged 5-17 years over the past decade (2010-2021) and to investigate whether there have been differences in temporal changes based on race and ethnicity, sex, or income. STUDY DESIGN: Childhood ADHD diagnosis was ascertained from electronic health records using International Classification of Diseases ninth revision (314.xx) and International Classification of Diseases tenth revision (F90.x) codes. Data were stratified by child's sex, race and ethnicity, and household income, and rates of ADHD were estimated before and after adjustment for potential confounders. RESULTS: The overall ADHD diagnosis rates increased from 3.5% in 2010 to 4.0% in 2021. ADHD diagnosis was most prevalent among White children (6.1%), then Black (4.6%), Other/multiple (3.7%), Hispanic (3.1%), and Asian/Pacific Islander (PI) (1.7%). ADHD was also highly prevalent among boys (73.3%) or family income≥$70,000 (50.0%). ADHD diagnosis increased among Black (4.2% to 5.1%), Hispanic (2.8% to 3.6%), and Asian/PI children (1.5% to 2.0%) but remained stable for White (6.2% to 6.1%) and Other/multiple race/ethnic children (3.7% to 3.7%). Increases in the prevalence among girls were also observed. CONCLUSION: The prevalence of ADHD in children has risen with the largest increases observed for Black, Hispanic, and Asian/PI children. Rates among less affluent families and girls have also been increasing, narrowing the gaps in diagnosis rates previously observed. These increases may reflect improvements in screening and provision of care among demographics where ADHD has been historically underdiagnosed.

Placental abruption: Incidence and risk of recurrence in subsequent pregnancies.

AIM: To estimate the incidence of abruption in first births and recurrence in the subsequent birth in patients of a large US-based integrated health care system. METHODS: Retrospective population-based cohort study of patients with first two consecutive singleton births using data from the Kaiser-Permanente South California health care system who delivered over a period of 30 years (1991-2021), using longitudinally linked electronic health records. ICD-9/ICD-10 codes "641.20" and "O45.x" identified placental abruption. We calculated the incidence and rates of abruption in first and second pregnancies. We used logistic regression to estimate the adjusted odds ratios (aOR) for abruption in second pregnancies in patients with and without abruptions in their first pregnancies. RESULTS: Of the 126 264 patients with first two consecutive singleton births over the period, 805 had abruptions in their first births, and 861 in their second births. Rates of abruption in first and second births were 0.63% and 0.68%, respectively. Twenty-seven patients had abruptions in both first and second births. Rates of abruption in the second birth among individuals with and without previous placental abruption were 3.35% and 0.66%, respectively, giving an approximately five-fold increased odds of abruption in a second pregnancy in individuals who had abruption in their first birth when compared with those who did not have placental abruption in their first birth (aOR: 4.95, 95% confidence interval: 3.35-7.31, p < 0.00001). Interpregnancy interval had no statistically significant association with recurrence. CONCLUSION: Abruption in a first birth is associated with an approximately five-fold increased odds of abruption in a second birth.

Adenomyosis in women undergoing hysterectomy for abnormal uterine bleeding associated with uterine leiomyomas.

BACKGROUND: Uterine leiomyomas and adenomyosis are both common and often associated with abnormal uterine bleeding (AUB), including the symptom of heavy menstrual bleeding (HMB). Understanding the prevalence of adenomyosis in women with uterine leiomyomas could inform clinicians and patients in a way that may improve therapeutic approaches. OBJECTIVE: To explore the prevalence of adenomyosis in a group of women who underwent hysterectomy for AUB-L, to determine the prevalence of submucous leiomyomas, and to examine the utility of preoperative ultrasound to detect the presence of adenomyosis. METHODS: The Kaiser Permanente Hysterectomy Database (KPHD) was searched for women aged 18-52 undergoing hysterectomy for leiomyoma-associated chronic AUB (AUB-L) in 2018 and 2019. A target sample of 400 comprised those with at least 3 years in the Health System. Radiologists evaluated preoperative pelvic ultrasound images to determine leiomyoma size and level 2 FIGO type (submucous or other), and the linked electronic medical record abstracted for clinical features, including histopathological evidence of adenomyosis. RESULTS: Of the 370 subjects that met the study criteria, adenomyosis was identified via histopathology in 170 (45.9%). There was no difference in the adenomyosis prevalence with (47.1%) and without (43.0%) at least one submucous leiomyoma. Subgroup analysis of ultrasound images by an expert radiologist for the presence of adenomyosis demonstrated a positive predictive value of 54.0% and a negative predictive value of 43.4%. CONCLUSIONS: Adenomyosis was present in almost half of this AUB-L cohort undergoing hysterectomy and was equally prevalent in those with and without submucous leiomyomas as determined by sonographic evaluation. The imaging findings are in accord with prior investigators and demonstrate that 2-D ultrasound is insensitive to the presence of adenomyosis when the uterus is affected by leiomyomas. Further research is necessary to determine the impact of various adenomyosis phenotypes on the presence and severity of the symptom of HMB.

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.

Risks of Uterine Perforation and Expulsion Associated With Intrauterine Devices.

OBJECTIVE: The APEX-IUD (Association of Perforation and Expulsion of Intrauterine Devices) study evaluated the association of postpartum timing of intrauterine device (IUD) insertion, breastfeeding, heavy menstrual bleeding, and IUD type (levonorgestrel-releasing vs copper) with risks of uterine perforation and IUD expulsion in usual clinical practice. We summarize the clinically important findings to inform counseling and shared decision making. METHODS: APEX-IUD was a real-world (using U.S. health care data) retrospective cohort study of individuals aged 50 years and younger with IUD insertions between 2001 and 2018 and with electronic health record data. Cumulative incidences of uterine perforation and IUD expulsion were calculated. Adjusted hazard ratios (aHRs) and 95% CIs were estimated from proportional hazards models with control of confounding. RESULTS: Among the study population of 326,658, absolute risk of uterine perforation was low overall (cumulative incidence, 0.21% [95% CI 0.19-0.23%] at 1 year and 0.61% [95% CI 0.56-0.66% at 5 years]) but was elevated for IUDs inserted during time intervals within 1 year postpartum, particularly among those between 4 days and 6 weeks postpartum (aHR 6.71, 95% CI 4.80-9.38), relative to nonpostpartum insertions. Among postpartum insertions, IUD expulsion risk was greatest for insertions in the immediate postpartum period (0-3 days after delivery) compared with nonpostpartum (aHR 5.34, 95% CI 4.47-6.39). Postpartum individuals who were breastfeeding had a slightly elevated risk of perforation and lowered risk of expulsion than those not breastfeeding. Among nonpostpartum individuals, those with a heavy menstrual bleeding diagnosis were at greater risk of expulsion than those without (aHR 2.84, 95% CI 2.66-3.03); heavy menstrual bleeding also was associated with a slightly elevated perforation risk. There was a slightly elevated perforation risk and slightly lower expulsion risk associated with levonorgestrel-releasing IUDs compared with copper IUDs. CONCLUSION: Absolute risk of adverse outcomes with IUD insertion is low. Clinicians should be aware of the differences in risks of uterine perforation and expulsion associated with IUD insertion during specific postpartum time periods and with a heavy menstrual bleeding diagnosis. This information should be incorporated into counseling and decision making for patients considering IUD insertion. FUNDING SOURCE: Bayer AG. CLINICAL TRIAL REGISTRATION: EU PAS register, EUPAS33461.

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.

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.

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.

The Effect of Neonatal Sepsis on Risk of Autism Diagnosis.

OBJECTIVE: The study aimed to examine the association between neonatal sepsis and autism risk among children and whether the risk varied with the timing of exposure, child's sex, and race/ethnicity. STUDY DESIGN: We conducted a retrospective cohort study using electronic health records (EHR) extracted from Kaiser Permanente Southern California Health Care System. Mother-child dyads were constructed by linking records of children born to member mothers and continuing to receive care through the system during the follow-up period with those of their biological mothers (n = 469,789). Clinical health records were used to define neonatal sepsis. Diagnosis of autism was made by medical specialists. Potential confounders included maternal sociodemographic factors, obstetrical history, child's age, sex, race/ethnicity, and maternal and child medical history. Incident rates and adjusted hazard ratios (aHR) were used to estimate the associations. RESULTS: Compared with children without the diagnosis of autism, children with the condition were more likely to be from Asian/Pacific Islander descent and male sex. Exposed children showed higher rates of autism as compared with unexposed children (3.43 vs. 1.73 per 1,000 person-years, aHR: 1.67-95% confidence interval [CI]: 1.39-2.00). Both preterm (aHR: 1.47; 95% CI: 1.09-1.98) and term (aHR: 1.63; 95% CI: 1.29-2.06) births were associated with increased risk for autism. Although the magnitude of the HRs and incidence ratios for neonatal sepsis to increase autism risk varied between race ethnicities, neonatal sepsis was associated with significantly increased likelihood of autism diagnosis for all race-ethic groups except for Asian/Pacific Islanders. Although neonatal sepsis was associated with significantly increased autism risk for both boys and girls, incident rates and HR point estimates suggested that the effect may be stronger in girls. CONCLUSION: Neonatal sepsis is associated with increased risk of autism diagnosis in preterm- and term-born children. The association was significant for both girls and boys and all race ethnicities except for Asian-Pacific Islanders. KEY POINTS: · Neonatal sepsis is associated with increased risk of autism diagnosis.. · The association was significant in preterm- and term-born children.. · The association was significant for all race/ethnicities except for Asian-Pacific Islanders..

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.

Hyperemesis Gravidarum: Risk of Recurrence in Subsequent Pregnancies.

This study aimed to examine whether the recurrence risk of hyperemesis gravidarum (HG) is modified by the timing of diagnosis, the severity of illness, and interpregnancy interval. The Kaiser Permanente Southern California 1998-2020 longitudinally linked medical records were used to examine the recurrence risk of HG in the first two (n = 93,444) and first three (n = 17,492) successive pregnancies. The timing of diagnosis- and the severity of illness-specific recurrence risks were examined by estimating the adjusted relative risks (aRR). The risks of HG in the second pregnancy among patients with and without previous HG were 23.8% and 3.4%, respectively (aRR: 8.20; 95% confidence interval [CI]: 7.52, 8.94). The recurrence risk persisted regardless of the trimester at diagnosis and the gestational age of delivery in the first pregnancy. The recurrence risk was greater for patients with metabolic disturbances requiring in-hospital treatment (30.0%) than those managed on an outpatient basis (18.6%) in the first pregnancy (aRR: 10.84 95% CI: 9.66, 12.16). Although Asian/Pacific Islander (RR = 12.9) and White (RR = 8.9) patients had higher HG recurrence risk regardless of the gestational age at delivery in the first pregnancy, all patients had significant recurrence risk only if their first pregnancy was delivered after 32 weeks of gestation. African American patients had the highest recurrence rate (34.4%). HG recurrence risk was unaffected by interpregnancy interval and correlated with the number of previous pregnancies complicated by HG. There is an increased recurrence risk of HG in subsequent pregnancies that is influenced by race/ethnicity and gestational age at delivery. The number of pregnancies complicated by HG synergistically adds to the recurrence risk.