Obstetric Complications and Birth Outcomes After Antenatal Coronavirus Disease 2019 (COVID-19) Vaccination.

OBJECTIVE: To evaluate the association between antenatal messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination and risk of adverse pregnancy outcomes. METHODS: This was a retrospective cohort study of individuals with singleton pregnancies with live deliveries between June 1, 2021, and January 31, 2022, with data available from eight integrated health care systems in the Vaccine Safety Datalink. Vaccine exposure was defined as receipt of one or two mRNA COVID-19 vaccine doses (primary series) during pregnancy. Outcomes were preterm birth (PTB) before 37 weeks of gestation, small-for-gestational age (SGA) neonates, gestational diabetes mellitus (GDM), gestational hypertension, and preeclampsia-eclampsia-HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Outcomes in individuals vaccinated were compared with those in propensity-matched individuals with unexposed pregnancies. Adjusted hazard ratios (aHRs) and 95% CIs were estimated for PTB and SGA using a time-dependent covariate Cox model, and adjusted relative risks (aRRs) were estimated for GDM, gestational hypertension, and preeclampsia-eclampsia-HELLP syndrome using Poisson regression with robust variance. RESULTS: Among 55,591 individuals eligible for inclusion, 23,517 (42.3%) received one or two mRNA COVID-19 vaccine doses during pregnancy. Receipt of mRNA COVID-19 vaccination varied by maternal age, race, Hispanic ethnicity, and history of COVID-19. Compared with no vaccination, mRNA COVID-19 vaccination was associated with a decreased risk of PTB (rate: 6.4 [vaccinated] vs 7.7 [unvaccinated] per 100, aHR 0.89; 95% CI, 0.83-0.94). Messenger RNA COVID-19 vaccination was not associated with SGA (8.3 vs 7.4 per 100; aHR 1.06, 95% CI, 0.99-1.13), GDM (11.9 vs 10.6 per 100; aRR 1.00, 95% CI, 0.90-1.10), gestational hypertension (10.8 vs 9.9 per 100; aRR 1.08, 95% CI, 0.96-1.22), or preeclampsia-eclampsia-HELLP syndrome (8.9 vs 8.4 per 100; aRR 1.10, 95% CI, 0.97-1.24). CONCLUSION: Receipt of an mRNA COVID-19 vaccine during pregnancy was not associated with an increased risk of adverse pregnancy outcomes; this information will be helpful for patients and clinicians when considering COVID-19 vaccination in pregnancy.

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.

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.

Discontinuation of Car Seat Tolerance Screening and Postdischarge Adverse Outcomes in Infants Born Preterm.

OBJECTIVE: To study the association between discontinuing predischarge car seat tolerance screening (CSTS) with 30-day postdischarge adverse outcomes in infants born preterm. STUDY DESIGN: Retrospective cohort study involving all infants born preterm from 2010 through 2021 who survived to discharge to home in a 14-hospital integrated health care system. The exposure was discontinuation of CSTS. The primary outcome was a composite rate of death, 911 call-triggered transports, or readmissions associated with diagnostic codes of respiratory disorders, apnea, apparent life-threatening event, or brief resolved unexplained events within 30 days of discharge. Outcomes of infants born in the periods of CSTS and after discontinuation were compared. RESULTS: Twelve of 14 hospitals initially utilized CSTS and contributed patients to the CSTS period; 71.4% of neonatal intensive care unit (NICU) patients and 26.9% of non-NICU infants were screened. All hospitals participated in the discontinuation period; 0.1% was screened. Rates of the unadjusted primary outcome were 1.02% in infants in the CSTS period (n = 21 122) and 1.06% after discontinuation (n = 20 142) (P = .76). The aOR (95% CI) was 0.95 (0.75, 1.19). Statistically insignificant differences between periods were observed in components of the primary outcome, gestational age strata, NICU admission status groups, and other secondary analyses. CONCLUSIONS: Discontinuation of CSTS in a large integrated health care network was not associated with a change in 30-day postdischarge adverse outcomes. CSTS's value as a standard predischarge assessment deserves further evaluation.

Prevalence of self-inflicted injuries among transgender and gender diverse adolescents and young adults compared to their peers: an examination of interaction with mental health morbidity.

PURPOSE: Compare occurrence of self-inflicted injuries among transgender and gender diverse (TGD) youth to that of their cisgender peers while accounting for mental health diagnoses. METHODS: Review of electronic health records from three integrated health care systems identified 1087 transfeminine and 1431 transmasculine adolescents and young adults. Poisson regression was used to calculate prevalence ratios comparing the proportion of TGD participants with at least one self-inflicted injury (a surrogate for suicide attempt) before index date (first evidence of TGD status) to the corresponding proportions in presumed cisgender male and female referents matched on age, race/ethnicity, and health plan. Interactions between gender identities and mental health diagnoses were assessed on multiplicative and additive scales. RESULTS: TGD adolescents and young adults were more likely to have a self-inflicted injury, various mental health diagnoses, and multiple mental health diagnoses than their cisgender peers. The prevalence of self-inflicted injuries among TGD adolescents and young adults was high even in the absence of mental health diagnoses. Results were consistent with positive additive interaction and negative multiplicative interaction. CONCLUSIONS: Universal suicide prevention efforts for all youth, including those with no mental health diagnoses, and more intensive suicide prevention efforts for TGD adolescents and young adults and those with at least one mental health diagnosis are warranted.

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.

Demographic, Reproductive, and Medical Risk Factors for Intrauterine Device Expulsion.

OBJECTIVE: To explore to what extent intrauterine device (IUD) expulsion is associated with demographic and clinical risk factors. METHODS: The APEX-IUD (Association of Perforation and Expulsion of IntraUterine Devices) study was a U.S. cohort study using electronic health records from three integrated health care systems (Kaiser Permanente Northern California, Southern California, and Washington) and a health care information exchange (Regenstrief Institute). These analyses included individuals aged 50 years or younger with IUD insertions from 2001 to 2018. Intrauterine device expulsion cumulative incidence and incidence rates were estimated. Using Cox regression models, hazard ratios with 95% CIs were estimated before and after adjustment for risk factors of interest (age, race and ethnicity, parity, body mass index [BMI], heavy menstrual bleeding, and dysmenorrhea) and potential confounders. RESULTS: In total, 228,834 individuals with IUD insertion and no delivery in the previous 52 weeks were identified (184,733 [80.7%] with levonorgestrel-releasing intrauterine system). Diagnosis of heavy menstrual bleeding-particularly a diagnosis in both recent and past periods-was the strongest risk factor for IUD expulsion. Categories with the highest risk of IUD expulsion within each risk factor included individuals diagnosed with overweight, obesity, and morbid obesity; those in younger age groups, especially among those aged 24 years or younger; and in those with parity of four or more. Non-Hispanic White individuals had the lowest incidence and risk, and after adjustment, Asian or Pacific Islander individuals had the highest risk. Dysmenorrhea was not independently associated with expulsion risk when adjusting for heavy menstrual bleeding. CONCLUSION: Most risk factors for expulsion identified in this study appear consistent with known physiologic factors that affect uterine anatomy and physiology (age, BMI, heavy menstrual bleeding, parity). The increased risk of IUD expulsion among individuals of color warrants further investigation. Intrauterine devices are an effective long-term contraceptive; expulsion is uncommon, but patients should be counseled accordingly. FUNDING SOURCE: Bayer AG. CLINICAL TRIAL REGISTRATION: EU PAS register, EUPAS33461.

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.

Cohort profile: pathways to care among people with disorders of sex development (DSD).

PURPOSE: The 'DSD Pathways' study was initiated to assess health status and patterns of care among people enrolled in large integrated healthcare systems and diagnosed with conditions comprising the broad category of disorders (differences) of sex development (DSD). The objectives of this communication are to describe methods of cohort ascertainment for two specific DSD conditions-classic congenital adrenal hyperplasia with 46,XX karyotype (46,XX CAH) and complete androgen insensitivity syndrome (CAIS). PARTICIPANTS: Using electronic health records we developed an algorithm that combined diagnostic codes, clinical notes, laboratory data and pharmacy records to assign each cohort candidate a 'strength-of-evidence' score supporting the diagnosis of interest. A sample of cohort candidates underwent a review of the full medical record to determine the score cutoffs for final cohort validation. FINDINGS TO DATE: Among 5404 classic 46,XX CAH cohort candidates the strength-of-evidence scores ranged between 0 and 10. Based on sample validation, the eligibility cut-off for full review was set at the strength-of-evidence score of ≥7 among children under the age of 8 years and ≥8 among older cohort candidates. The final validation of all cohort candidates who met the cut-off criteria identified 115 persons with classic 46,XX CAH. The strength-of-evidence scores among 648 CAIS cohort candidates ranged from 2 to 10. There were no confirmed CAIS cases among cohort candidates with scores <6. The in-depth medical record review for candidates with scores ≥6 identified 61 confirmed cases of CAIS. FUTURE PLANS: As the first cohort of this type, the DSD Pathways study is well-positioned to fill existing knowledge gaps related to management and outcomes in this heterogeneous population. Analyses will examine diagnostic and referral patterns, adherence to care recommendations and physical and mental health morbidities examined through comparisons of DSD and reference populations and analyses of health status across DSD categories.

Association between intrauterine device type and risk of perforation and device expulsion: results from the Association of Perforation and Expulsion of Intrauterine Device study.

BACKGROUND: Intrauterine devices, including levonorgestrel-releasing and copper devices, are highly effective long-acting reversible contraceptives. The potential risks associated with intrauterine devices are low and include uterine perforation and device expulsion. OBJECTIVE: This study aimed to evaluate the risk of perforation and expulsion associated with levonorgestrel-releasing devices vs copper devices in clinical practice in the United States. STUDY DESIGN: The Association of Perforation and Expulsion of Intrauterine Device study was a retrospective cohort study of women aged ≤50 years with an intrauterine device insertion during 2001 to 2018 and information on intrauterine device type and patient and medical characteristics. Of note, 4 research sites with access to electronic health records contributed data for the study: 3 Kaiser Permanente-integrated healthcare systems (Northern California, Southern California, and Washington) and 1 healthcare system using data from a healthcare information exchange in Indiana (Regenstrief Institute). Perforation was classified as any extension of the device into or through the myometrium. Expulsion was classified as complete (not visible in the uterus or abdomen or patient reported) or partial (any portion in the cervix or malpositioned). We estimated the crude incidence rates and crude cumulative incidence by intrauterine device type. The risks of perforation and expulsion associated with levonorgestrel-releasing intrauterine devices vs copper intrauterine devices were estimated using Cox proportional-hazards regression with propensity score overlap weighting to adjust for confounders. RESULTS: Among 322,898 women included in this analysis, the incidence rates of perforation per 1000 person-years were 1.64 (95% confidence interval, 1.53-1.76) for levonorgestrel-releasing intrauterine devices and 1.27 (95% confidence interval, 1.08-1.48) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 0.22% (95% confidence interval, 0.20-0.24) and 0.63% (95% confidence interval, 0.57-0.68) for levonorgestrel-releasing intrauterine devices and 0.16% (95% confidence interval, 0.13-0.20) and 0.55% (95% confidence interval, 0.44-0.68) for copper intrauterine devices, respectively. The incidence rates of expulsion per 1000 person-years were 13.95 (95% confidence interval, 13.63-14.28) for levonorgestrel-releasing intrauterine devices and 14.08 (95% confidence interval, 13.44-14.75) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 2.30% (95% confidence interval, 2.24-2.36) and 4.52% (95% confidence interval, 4.40-4.65) for levonorgestrel-releasing intrauterine devices and 2.30% (95% confidence interval, 2.18-2.44) and 4.82 (95% confidence interval, 4.56-5.10) for copper intrauterine devices, respectively. Comparing levonorgestrel-releasing intrauterine devices with copper intrauterine devices, the adjusted hazard ratios were 1.49 (95% confidence intervals, 1.25-1.78) for perforation and 0.69 (95% confidence intervals, 0.65-0.73) for expulsion. CONCLUSION: After adjusting for potential confounders, levonorgestrel-releasing intrauterine devices were associated with an increased risk of uterine perforation and a decreased risk of expulsion relative to copper intrauterine devices. Given that the absolute numbers of these events are low in both groups, these differences may not be clinically meaningful.

Association between menorrhagia and risk of intrauterine device-related uterine perforation and device expulsion: results from the Association of Uterine Perforation and Expulsion of Intrauterine Device study.

BACKGROUND: Intrauterine devices are effective instruments for contraception, and 1 levonorgestrel-releasing device is also indicated for the treatment of heavy menstrual bleeding (menorrhagia). OBJECTIVE: To compare the incidence of intrauterine device expulsion and uterine perforation in women with and without a diagnosis of menorrhagia within the first 12 months before device insertion STUDY DESIGN: This was a retrospective cohort study conducted in 3 integrated healthcare systems (Kaiser Permanente Northern California, Southern California, and Washington) and a healthcare information exchange (Regenstrief Institute) in the United States using electronic health records. Nonpostpartum women aged ≤50 years with intrauterine device (eg, levonorgestrel or copper) insertions from 2001 to 2018 and without a delivery in the previous 12 months were studied in this analysis. Recent menorrhagia diagnosis (ie, recorded ≤12 months before insertion) was ascertained from the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes. The study outcomes, viz, device expulsion and device-related uterine perforation (complete or partial), were ascertained from electronic medical records and validated in the data sources. The cumulative incidence and crude incidence rates with 95% confidence intervals were estimated. Cox proportional hazards models estimated the crude and adjusted hazard ratios using propensity score overlap weighting (13-16 variables) and 95% confidence intervals. RESULTS: Among 228,834 nonpostpartum women, the mean age was 33.1 years, 44.4% of them were White, and 31,600 (13.8%) had a recent menorrhagia diagnosis. Most women had a levonorgestrel-releasing device (96.4% of those with and 78.2% of those without a menorrhagia diagnosis). Women with a menorrhagia diagnosis were likely to be older, obese, and have dysmenorrhea or fibroids. Women with a menorrhagia diagnosis had a higher intrauterine device-expulsion rate (40.01 vs 10.92 per 1000 person-years) than those without, especially evident in the first few months after insertion. Women with a menorrhagia diagnosis had a higher cumulative incidence (95% confidence interval) of expulsion (7.00% [6.70-7.32] at 1 year and 12.03% [11.52-12.55] at 5 years) vs those without (1.77% [1.70-1.84] at 1 year and 3.69% [3.56-3.83] at 5 years). The risk of expulsion was increased for women with a menorrhagia diagnosis vs for those without (adjusted hazard ratio, 2.84 [95% confidence interval, 2.66-3.03]). The perforation rate was low overall (<1/1000 person-years) but higher in women with a diagnosis of menorrhagia vs in those without (0.98 vs 0.63 per 1000 person-years). The cumulative incidence (95% confidence interval) of uterine perforation was slightly higher for women with a menorrhagia diagnosis (0.09% [0.06-0.14] at 1 year and 0.39% [0.29-0.53] at 5 years) than those without it (0.07% [0.06-0.08] at 1 year and 0.28% [0.24-0.33] at 5 years). The risk of perforation was slightly increased in women with a menorrhagia diagnosis vs in those without (adjusted hazard ratio, 1.53; 95% confidence interval, 1.10-2.13). CONCLUSION: The risk of expulsion is significantly higher in women with a recent diagnosis of menorrhagia. Patient education and counseling regarding the potential expulsion risk is recommended at insertion. The absolute risk of perforation for women with a recent diagnosis of menorrhagia is very low. The increased expulsion and perforation rates observed are likely because of causal factors of menorrhagia.

Receipt of COVID-19 Vaccine During Pregnancy and Preterm or Small-for-Gestational-Age at Birth - Eight Integrated Health Care Organizations, United States, December 15, 2020-July 22, 2021.

COVID-19 vaccines are recommended during pregnancy to prevent severe maternal morbidity and adverse birth outcomes; however, vaccination coverage among pregnant women has been low (1). Concerns among pregnant women regarding vaccine safety are a persistent barrier to vaccine acceptance during pregnancy. Previous studies of maternal COVID-19 vaccination and birth outcomes have been limited by small sample size (2) or lack of an unvaccinated comparison group (3). In this retrospective cohort study of live births from eight Vaccine Safety Datalink (VSD) health care organizations, risks for preterm birth (<37 weeks' gestation) and small-for-gestational-age (SGA) at birth (birthweight <10th percentile for gestational age) after COVID-19 vaccination (receipt of ≥1 COVID-19 vaccine doses) during pregnancy were evaluated. Risks for preterm and SGA at birth among vaccinated and unvaccinated pregnant women were compared, accounting for time-dependent vaccine exposures and propensity to be vaccinated. Single-gestation pregnancies with estimated start or last menstrual period during May 17-October 24, 2020, were eligible for inclusion. Among 46,079 pregnant women with live births and gestational age available, 10,064 (21.8%) received ≥1 COVID-19 vaccine doses during pregnancy and during December 15, 2020-July 22, 2021; nearly all (9,892; 98.3%) were vaccinated during the second or third trimester. COVID-19 vaccination during pregnancy was not associated with preterm birth (adjusted hazard ratio [aHR] = 0.91; 95% CI = 0.82-1.01). Among 40,627 live births with birthweight available, COVID-19 vaccination in pregnancy was not associated with SGA at birth (aHR = 0.95; 95% CI = 0.87-1.03). Results consistently showed no increased risk when stratified by mRNA COVID-19 vaccine dose, or by second or third trimester vaccination, compared with risk among unvaccinated pregnant women. Because of the small number of first-trimester exposures, aHRs for first-trimester vaccination could not be calculated. These data add to the evidence supporting the safety of COVID-19 vaccination during pregnancy. To reduce the risk for severe COVID-19-associated illness, CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant (including those who are lactating), who are trying to become pregnant now, or who might become pregnant in the future (4).

Is There a Link Between Hormone Use and Diabetes Incidence in Transgender People? Data From the STRONG Cohort.

BACKGROUND: Risk of type 2 diabetes mellitus (T2DM) in transgender and gender diverse (TGD) persons, especially those receiving gender-affirming hormone therapy (GAHT) is an area of clinical and research importance. METHODS: We used data from an electronic health record-based cohort study of persons 18 years and older enrolled in 3 integrated health care systems. The cohort included 2869 transfeminine members matched to 28 300 cisgender women and 28 258 cisgender men on age, race/ethnicity, calendar year, and site, and 2133 transmasculine members similarly matched to 20 997 cisgender women and 20 964 cisgender men. Cohort ascertainment spanned 9 years from 2006 through 2014 and follow-up extended through 2016. Data on T2DM incidence and prevalence were analyzed using Cox proportional hazards and logistic regression models, respectively. All analyses controlled for body mass index. RESULTS: Both prevalent and incident T2DM was more common in the transfeminine cohort relative to cisgender female referents with odds ratio and hazard ratio (95% CI) estimates of 1.3 (1.1-1.5) and 1.4 (1.1-1.8), respectively. No significant differences in prevalence or incidence of T2DM were observed across the remaining comparison groups, both overall and in TGD persons with evidence of GAHT receipt. CONCLUSION: Although transfeminine people may be at higher risk for T2DM compared with cisgender females, the corresponding difference relative to cisgender males is not discernable. Moreover, there is little evidence that T2DM occurrence in either transfeminine or transmasculine persons is attributable to GAHT use.

Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy.

BACKGROUND: The effect of gender affirming hormone therapy (GAHT) on clinical laboratory parameters, including levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), is an area of uncertainty in transgender health. AIM: We sought to estimate the distribution parameters of liver enzyme levels among transmasculine (TM) and transfeminine (TF) persons receiving GAHT relative to the corresponding measures in cisgender reference groups, and to evaluate longitudinal changes in these laboratory measures following GAHT initiation. METHODS: The data for this longitudinal study included 624 TF and 438 transmasculine (TM) people as well as 4,090 cisgender males and 4,797 cisgender females enrolled in 3 integrated health systems. Time under observation was divided into 2 intervals: from the first blood test to the date of the first filled GAHT prescription and from GAHT initiation to the most recent ALT or AST measurement. Linear mixed models were used to compare changes in log-transformed ALT and AST values among transgender cohort members before and after GAHT initiation, and relative to the reference groups. The results were expressed as relative differences (in %) and the ratios of these differences (ratios-of-ratios) along with the 95% confidence intervals (CIs). OUTCOMES: Changes in ALT and AST levels among transgender people over time and relative to the corresponding changes in cisgender referents. RESULTS: Among TM study participants, the post GAHT ratios-of-ratios for AST were 1.61 (95% CI: 1.13, 2.31) and 1.57 (95% CI: 1.06, 2.31) relative to cisgender males and females respectively. For ALT, the corresponding comparisons yielded the ratios-of-ratios (95% CIs) of 2.06 (1.67, 2.54) and 1.90 (1.50, 2.40). No statistically significant changes were observed among TF participants. Other factors associated with higher liver enzyme levels included alcohol use/abuse and obesity. CLINICAL IMPLICATIONS: TM persons may experience modest increases in ALT and AST concentrations following testosterone initiation; however, clinical significance of the observed association remains unclear and requires further investigation. By contrast, feminizing GAHT is unlikely to induce appreciable changes in liver enzyme levels. STRENGTH AND LIMITATIONS: The strengths of this study are the longitudinal design and the ability to assemble an unselected cohort nested within large health systems. The main limitations include the lack of information on hormone levels and the inability to take into account GAHT doses and routes of administration. CONCLUSION: The influence of long-term GAHT on ALT and AST levels appears modest and not likely to reflect clinically meaningful changes in liver function. Hashemi L, Zhang Q, Getahun D, et al. Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy. J Sex Med 2021;18:1662-1675.

COVID-19 Vaccination Coverage Among Pregnant Women During Pregnancy - Eight Integrated Health Care Organizations, United States, December 14, 2020-May 8, 2021.

COVID-19 vaccines are critical for ending the COVID-19 pandemic; however, current data about vaccination coverage and safety in pregnant women are limited. Pregnant women are at increased risk for severe illness and death from COVID-19 compared with nonpregnant women of reproductive age, and are at risk for adverse pregnancy outcomes, such as preterm birth (1-4). Pregnant women are eligible for and can receive any of the three COVID-19 vaccines available in the United States via Emergency Use Authorization.* Data from Vaccine Safety Datalink (VSD), a collaboration between CDC and multiple integrated health systems, were analyzed to assess receipt of ≥1 dose (first or second dose of the Pfizer-BioNTech or Moderna vaccines or a single dose of the Janssen [Johnson & Johnson] vaccine) of any COVID-19 vaccine during pregnancy, receipt of first dose of a 2-dose COVID-19 vaccine (initiation), or completion of a 1- or 2-dose COVID-19 vaccination series. During December 14, 2020-May 8, 2021, a total of 135,968 pregnant women were identified, 22,197 (16.3%) of whom had received ≥1 dose of a vaccine during pregnancy. Among these 135,968 women, 7,154 (5.3%) had initiated and 15,043 (11.1%) had completed vaccination during pregnancy. Receipt of ≥1 dose of COVID-19 vaccine during pregnancy was highest among women aged 35-49 years (22.7%) and lowest among those aged 18-24 years (5.5%), and higher among non-Hispanic Asian (Asian) (24.7%) and non-Hispanic White (White) women (19.7%) than among Hispanic (11.9%) and non-Hispanic Black (Black) women (6.0%). Vaccination coverage increased among all racial and ethnic groups over the analytic period, likely because of increased eligibility for vaccination† and increased availability of vaccine over time. These findings indicate the need for improved outreach to and engagement with pregnant women, especially those from racial and ethnic minority groups who might be at higher risk for severe health outcomes because of COVID-19 (4). In addition, providing accurate and timely information about COVID-19 vaccination to health care providers, pregnant women, and women of reproductive age can improve vaccine confidence and coverage by ensuring optimal shared clinical decision-making.

Changes in Size and Demographic Composition of Transgender and Gender Non-Binary Population Receiving Care at Integrated Health Systems.

OBJECTIVE: To examine temporal changes in the number and demographic composition of transgender/gender non-binary (TGNB) population using data from integrated health care systems. METHODS: Electronic health records from Kaiser Permanente health plans in Georgia and Northern and Southern California were used to identify TGNB individuals, who sought care from January 2006 to December 2014, and the data were analyzed by year, site, age, and sex assigned at birth. RESULTS: In 2006, the number of TGNB people (and corresponding 95% CI) per 100 000 population were 3.5 (1.9, 6.3) in Georgia, 5.5 (4.8, 6.4) in Southern California, and 17 (16, 19) in Northern California. In 2014, these frequencies increased to 38 (32, 45), 44 (42, 46), and 75 (72, 78) per 100 000 population, respectively. When analyzed by age, the most rapid increase was observed among persons 18 to 25 years old, and this increase accelerated after 2010. The ratio of transmasculine to transfeminine persons also changed from 1:1.7 in 2006 to 1:1 in 2014 overall and from 1:1 in 2006 to 1.8:1 in 2014 among persons <18 years of age. CONCLUSION: This analysis confirms previous observations that the proportion of TGNB people is growing, especially among young adults. The composition of the TGNB population is also changing from predominantly transfeminine to roughly 1:1 overall and to predominantly transmasculine in children and adolescents.