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.

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.

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..

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..

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.

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.

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..

Prenatal Influenza Vaccination or Influenza Infection and Autism Spectrum Disorder in Offspring.

BACKGROUND: As prenatal vaccinations continue to be given more frequently, it is important to assess long-term safety events. We investigated the association between prenatal influenza vaccination or infection and autism spectrum disorder (ASD) in offspring. METHODS: A retrospective cohort study of mother-child pairs with deliveries between 1 January 2011 and 31 December 2014 at Kaiser Permanente Southern California was performed. Children aged >1 year were followed through 31 December 2018. Maternal influenza vaccination or infection during pregnancy was obtained from electronic health records. ASD was defined by International Classification of Diseases, Ninth or Tenth Revisions, Clinical Modification, codes after age 1 year. Cox proportional hazard models estimated the crude and inverse probability of treatment weighted (IPTW) hazard ratios (HR) for the association between maternal influenza vaccination or infection and ASD. RESULTS: There were 84 739 mother-child pairs included in the final analytic sample. Of the 46 257 women vaccinated, 32.4% were vaccinated during the first trimester, 41.8% during the second trimester, and 25.8% during the third trimester. ASD was diagnosed in 1930 (2.3%) children. The IPTW analyses showed no association between prenatal influenza vaccination or infection and ASD in offspring (HR, 1.04; 95% confidence interval [CI], .95-1.13; HR, 1.12; 95% CI, .66-1.89, respectively). CONCLUSIONS: Prenatal influenza vaccination or infection was not associated with ASD risk in offspring. The findings support recommendations to vaccinate pregnant women to protect themselves and their infants, both of whom are vulnerable to severe morbidity following infection.

Perinatal outcomes after bariatric surgery.

BACKGROUND: Bariatric surgery is a widely used treatment option for obesity that often provides long-term weight control and health benefits. Although a growing number of women are becoming pregnant after bariatric surgery, only a few population-based studies have assessed the impact thereof on perinatal outcomes. OBJECTIVE: This study aimed to examine the association between bariatric surgery and adverse perinatal outcomes in pregnant women and to examine whether the risk for adverse perinatal outcomes is modified by the postsurgery weight, gestational weight gain, type of bariatric surgery, timing of pregnancy after bariatric surgery, and maternal comorbidities. STUDY DESIGN: A retrospective cohort study was performed with the use of the Bariatric Surgery Registry and hospital inpatient and outpatient physician encounter records. The International Classification of Diseases, Ninth and Tenth Revision codes from hospitalizations during pregnancy and infant birth records were used to ascertain the outcomes of interest. Women eligible for BS who delivered at ≥20 weeks of gestation (n=20,213) at Kaiser Permanente Southern California hospitals (January 1, 2007 to December 31, 2018) were included in the study. Adjusted odds ratios were derived from logistic regression models with inverse probability of treatment weighting to adjust for confounding using propensity scores. RESULTS: Bariatric surgery was associated with a reduction in the risks for gestational diabetes (adjusted odds ratio, 0.60; 95% confidence interval, 0.53-0.69; P<.001), preeclampsia (adjusted odds ratio, 0.53; 95% confidence interval, 0.46-0.61; P<.001), chorioamnionitis (adjusted odds ratio, 0.45; 95% confidence interval, 0.32-0.63; P<.001), cesarean delivery (adjusted odds ratio, 0.65; 95% confidence interval, 0.59-0.72; P<.001), large for gestational age neonate (adjusted odds ratio, 0.23; 95% confidence interval, 0.19-0.29; P<.001), macrosomia (adjusted odds ratio, 0.24; 95% confidence interval, 0.19-0.30; P<.001), and neonatal intensive care unit admission (adjusted odds ratio, 0.70; 95% confidence interval, 0.61-0.81; P<.001). However, bariatric surgery was also associated with a significantly increased risk for small for gestational age neonates (adjusted odds ratio, 2.46; 95% confidence interval, 2.16-2.79; P<.001). The risk for the adverse outcomes is independent of the time interval between the surgery and subsequent pregnancy. CONCLUSION: These data suggest that there are many pregnancy outcome benefits for women with severe obesity who undergo bariatric surgery; however, women who have undergone bariatric surgery before pregnancy should be monitored closely to reduce the risk for small for gestational age neonates and postpartum hemorrhage.

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.

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 SARS-CoV-2 Infection and Adverse Perinatal Outcomes in a Large Health Maintenance Organization.

OBJECTIVE: This study aimed to examine whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy is associated with increased odds of perinatal complications and viral transmission to the infant. STUDY DESIGN: A retrospective cohort study of women who delivered at Kaiser Permanente Southern California hospitals (April 6, 2020-February 28, 2021) was performed using data extracted from electronic health records (EHRs). During this time polymerize chain reaction (PCR)-based tests for SARS-CoV-2 was universally offered to all pregnant women at labor and delivery admission, as well as earlier in the pregnancy, if they were displaying symptoms consistent with SARS-CoV-2 infection or a possible exposure to the virus. Adjusted odds ratio (aOR) was used to estimate the strength of associations between positive test results and adverse perinatal outcomes. RESULTS: Of 35,123 women with a singleton pregnancy, 2,203 (6%) tested positive for SARS-CoV-2 infection with 596 (27%) testing positive during the first or second trimester and 1,607 (73%) during the third trimester. Women testing positive were younger than those who tested negative (29.7 [5.4] vs. 31.1 [5.3] years; mean [standard deviation (SD)]; p < .001). The SARS-CoV-2 infection tended to increase the odds of an abnormal fetal heart rate pattern (aOR: 1.10; 95% confidence interval [CI]: 1.00, 1.21; p = 0.058), spontaneous preterm birth (aOR: 1.28; 95% CI: 1.03, 1.58; p = 0.024), congenital anomalies (aOR: 1.69; 95% CI: 1.15, 2.50; p = 0.008), and maternal intensive care unit admission at delivery (aOR: 7.44; 95% CI: 4.06, 13.62; p < 0.001) but not preeclampsia/eclampsia (aOR: 1.14; 95% CI: 0.98, 1.33; p = 0.080). Eighteen (0.8%) neonates of mothers who tested positive also had a positive SARS-CoV-2 test after 24 hours of birth, but all were asymptomatic during the neonatal period. CONCLUSION: These findings suggest that prenatal SARS-CoV-2 infection increases the odds of some adverse perinatal outcomes. The likelihood of vertical transmission from the mother to the fetus was low (0.3%), suggesting that pregnancy complications resulting from SARS-CoV-2 infection pose more risk to the baby than transplacental viral transmission. KEY POINTS: · SARS-CoV-2 infection is associated with increased odds of adverse perinatal outcomes.. · The odds of specific adverse outcomes were greater when a mother was infected earlier in pregnancy.. · The proportion of vertical transmission from mother to fetus was 0.3%.

Design of the Association of Uterine Perforation and Expulsion of Intrauterine Device study: a multisite retrospective cohort study.

BACKGROUND: Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006-2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration-mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device-related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion. OBJECTIVE: We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up. STUDY DESIGN: APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights. RESULTS: The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74-177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record. CONCLUSION: Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians.

Women with high plasma levels of PBDE-47 are at increased risk of preterm birth.

OBJECTIVES: Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. METHODS: Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. RESULTS: We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. CONCLUSIONS: These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.

Maternal Hypothyroidism Increases the Risk of Attention-Deficit Hyperactivity Disorder in the Offspring.

OBJECTIVE: This study aimed to determine if hypothyroidism prior to, or during, pregnancy increases the risk of attention-deficit hyperactivity disorder (ADHD) in the child and how the association may be modified by preterm birth, sex of the child, and race-ethnicity. STUDY DESIGN: Data were abstracted from linked maternal-child medical records. Incidence rate differences (IRDs), adjusted hazard ratios (aHRs), and their 95% confidence intervals (CIs) were estimated to evaluate the association of maternal hypothyroidism with childhood ADHD risk. Stratified analyses were used to evaluate whether the association is affected by timing of first diagnosis, gestational age at birth (term vs. preterm), sex, and race-ethnicity. RESULTS: Hypothyroidism diagnosed prior to (IRD = 1.30), or during (IRD = 0.59) pregnancy increases the risk of ADHD in the children (aHR = 1.27; 95% CI: 1.15, 1.41, and 1.17; 95% CI: 1.00, 1.38). The association was strongest when diagnosed during the first trimester (IRD = 0.97 and aHR = 1.28; 95% CI: 1.04, 1.58). For children born preterm, there was significantly increased risk of ADHD if their mothers were diagnosed prior to (IRD = 3.06 and aHR = 1.43; 95% CI: 1.09, 1.88), but not during pregnancy. The effect of maternal hypothyroidism on increased risk of ADHD was stronger for boys (IRD = 1.84 and aHR = 1.26; 95% CI: 1.14, 1.40) than it was for girls (IRD = 0.48 and aHR = 1.19; 95% CI: 1.01, 1.40) and for Hispanic children (IRD = 1.60 and aHR = 1.45; 95% CI: 1.25, 1.68) compared with other race ethnicities. CONCLUSION: Exposure to maternal hypothyroidism during the periconceptual period significantly increases the risk of ADHD and that the association varies with gestational age at delivery, child sex, and race-ethnicity. KEY POINTS: · Maternal hypothyroidism increases the risk of ADHD diagnosis in the offspring.. · The association of maternal hypothyroidism with childhood ADHD was influenced by timing of diagnosis.. · Strength of the association was strongest in preterm born infants, boys, and Hispanic children..

The Association of Prenatal Tetanus, Diphtheria, and Acellular Pertussis (Tdap) Vaccination With Attention-Deficit/Hyperactivity Disorder.

As prenatal vaccinations become more prevalent, it is important to assess potential safety events. In a retrospective cohort study of Kaiser Permanente Southern California (Pasadena, California) mother-child pairs with birth dates during January 1, 2011-December 31, 2014, we investigated the association between prenatal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Information on Tdap vaccination during pregnancy was obtained from electronic medical records. ADHD was defined by International Classification of Diseases codes (Ninth or Tenth Revision) and dispensed ADHD medication after age 3 years. Children were followed to the date of their first ADHD diagnosis, the end of Kaiser Permanente membership, or the end of follow-up (December 31, 2018). In Cox proportional hazards models, we estimated unadjusted and adjusted hazard ratios for the association between maternal Tdap vaccination and ADHD, with inverse probability of treatment weighting (IPTW) used to adjust for confounding. Of 128,756 eligible mother-child pairs, 85,607 were included in the final sample. The ADHD incidence rate was 3.41 per 1,000 person-years in the Tdap-vaccinated women and 3.93 per 1,000 person-years in the unvaccinated (hazard ratio = 1.01, 95% confidence interval: 0.88, 1.16). The IPTW-adjusted analyses showed no association between prenatal Tdap vaccination and ADHD in offspring (hazard ratio = 1.00, 95% confidence interval: 0.88, 1.14). In this study, prenatal Tdap vaccination was not associated with ADHD risk in offspring, supporting recommendations to vaccinate pregnant women.

Universal SARS-Cov-2 Screening in Women Admitted for Delivery in a Large Managed Care Organization.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has created a need for data regarding the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnant women. After implementing universal screening for COVID-19 in women admitted for delivery, we sought to describe the characteristics of COVID-19 in this large cohort of women. STUDY DESIGN: An observational study of women admitted to labor and delivery units in Kaiser Permanente Southern California (KPSC) hospitals between April 6 and May 11, 2020 who were universally offered testing for SARS-CoV-2 infection (n = 3,963). Hospital inpatient and outpatient physician encounter, and laboratory records were used to ascertain universal testing levels, test results, and medical and obstetrical histories. The prevalence of SARS-CoV-2 infection was estimated from the number of women who tested positive during labor per 100 women delivered. RESULTS: Of women delivered during the study period, 3,923 (99.0%) underwent SARS-CoV-2 testing. A total of 17 (0.43%; 95% confidence interval: 0.23-0.63%) women tested positive, and none of them were symptomatic on admission. There was no difference in terms of characteristics between SARS-CoV-2 positive and negative tested women. One woman developed a headache attributed to COVID-19 3 days postpartum. No neonates had a positive test at 24 hours of life. CONCLUSION: The findings suggest that in pregnant women admitted for delivery between April 6 and May 11, 2020 in this large integrated health care system in Southern California, prevalence of SARS-CoV-2 test positive was very low and all patients were asymptomatic on admission. KEY POINTS: · The prevalence of SARS-CoV-2 infection in a large diverse cohort of term pregnant women was 0.43%.. · 99% of women accepted SARS-CoV-2 screening on admission to labor and delivery.. · All women with positive test results were asymptomatic at the time of testing..

Association between maternal hypothyroidism and autism spectrum disorders in children.

BackgroundTo determine whether hypothyroidism is associated with autism spectrum disorders (ASD) and how this association is influenced by race-ethnicity, sex, and timing of exposure.MethodsA retrospective cohort study was conducted using records from 397,201 children who were delivered from 1991 to 2011 and remained health plan members from 1993 to 2014.ResultsChildren of hypothyroid women had higher ASD rates than children of women without the diagnosis (2.14 vs. 1.62/1,000 person-years; adjusted hazard ratios (adj.HR), 1.31; 95% confidence interval (CI), 1.13-1.53). This occurred in women diagnosed before as well as during pregnancy. Maternal hypothyroidism was associated with ASD for both boys (3.93 vs. 2.62/1,000 person-years; adj.HR, 1.27; 95% CI, 1.07-1.50) and girls (1.10 vs. 0.61/1,000 person-years; adj.HR, 1.51; 95% CI, 1.10-2.08). Of women with a diagnosis of hypothyroidism during pregnancy, normal thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels were not associated with an increased risk of ASD in children. Compared with white children, prenatal hypothyroidism was associated with an increased risk of ASD in children of Hispanics (adj.HR, 1.09; 95% CI, 1.01-1.17) and women of other/mixed race-ethnicity (adj.HR, 1.08; 95% CI, 1.00-1.16).ConclusionMaternal hypothyroidism is associated with ASD in children in a manner dependent on race-ethnicity. Management of maternal hypothyroidism may ameliorate the risk of ASD.

Association of Perinatal Risk Factors with Autism Spectrum Disorder.

Objective To examine the association between exposures to perinatal factors and autism spectrum disorders (ASD). Study Design A retrospective cohort study of ASD among children born in Kaiser Permanente Southern California hospitals between 1991 and 2009 (n = 594,638). Medical records were used to determine exposure to perinatal (antepartum and intrapartum) complications. ASD was diagnosed using DSM-IV criteria. Multivariable Cox regression was used to estimate hazard ratios (HRs). Result Children with ASD were more likely to be exposed to perinatal complications (HR = 1.15, 95% confidence interval [CI]: 1.09-1.21) than neurotypical children. Children exposed to antepartum (HR = 1.22, 95% CI: 1.10-1.36) and intrapartum (HR = 1.10, 95% CI: 1.04-1.17) complications were at increased risk of ASD. The risk was even greater when both antepartum and intrapartum conditions were present (HR = 1.44, 95% CI: 1.26-1.63). Conclusion Exposure to antepartum or intrapartum complications increases the risk of ASD in the offspring. Therefore, pregnancy complications may help identify children who could benefit from early screening and intervention for this common neurodevelopmental condition.