BACKGROUND:Neurodevelopmental conditions (NDC), including attention deficit/hyperactivity disorder (ADHD) and autism, are associated with increased rates of neurodegenerative diseases, including Alzheimer's disease and related dementias (ADRD) and Parkinson's disease. Such associations are unstudied in diverse populations and while controlling for a range of important covariates. The purpose of this study was to examine the association of ADRD and Parkinson's disease with NDCs in a diverse sample of adults. METHODS:This case-control study used data from the United States All of Us Research Program 2018-2023 from approximately 600 000 adults in the United States. We matched on ADRD and Parkinson's disease status to examine the association of these conditions with NDCs. RESULTS:NDC was more prevalent in ADRD cases than in non-ADRD controls (7.8% vs 2.4%) and among Parkinson's disease cases than non-Parkinson's disease controls (4.5% vs 1.8%). After adjustment for sex, age, education level, body mass index, cardiometabolic conditions, and psychiatric conditions, individuals with ADRD had significantly higher odds of having an NDC compared with controls (adjusted odds ratio, 2.68; 95% CI, 2.40-2.99). Similarly, Parkinson's disease cases had 2.09 times the odds of having an NDC as non-Parkinson's disease controls (95% CI 1.66, 2.59) in adjusted models. CONCLUSIONS:As the population of individuals with NDCs ages, and more older adults find themselves in the care of clinicians with expertise in ADRD and Parkinson's disease, it is imperative to understand the support needs of this population, and to provide targets for reducing ADRD prevalence in younger or middle adulthood.

Purpose: To examine changes in employment of caregivers of children with autism and children with special health care needs (CSHCN). Methods: This study used the National Survey of Children's Health to examine the prevalence of employment changes of caregivers, including reducing hours or stopping work and avoiding changing jobs to maintain insurance. We used multivariable logistic regression to estimate associations of care coordination with both employment outcomes. Finally, we examined differences by age and insurance type, stratified by care coordination status, to examine potential interaction of these variables in children with autism and CSHCN. Results: Caregivers of children with autism were more likely to experience changes in their employment than CSHCN. Caregivers who did not receive needed care coordination had 2.21 times the odds of reducing hours or stopping work than those who received needed care coordination (95% CI 1.89, 2.58). Age was also associated with employment changes for caregivers of children and autism and CSHCN. For caregivers of children with autism ages 3-5 years, the rate of reduced hours or stopped working was triple for those who did not receive needed care coordination (59%) compared to those who did (21%). Conclusions: Caregivers may reduce employment to support their child in receiving needed care. The findings from this study demonstrate the need for further research to examine the provision of care coordination and the cost-benefit analysis of public funding for care coordination to improve caregiver employment outcomes and create more support for families with a child with autism.

BACKGROUND:Although lithium has been used effectively as a medication to treat bipolar and major depressive disorders, there are limited data defining lithium use patterns during pregnancy. AIMS:To investigate trends and patterns of lithium prescribing in the perinatal period (before, during and after pregnancy) among pregnancies in the UK. METHOD:We conducted a population-based study using primary healthcare records from the Clinical Practice Research Datalink GOLD, analysing 752 112 pregnancies during the period 1995-2018. We assessed the prevalence and patterns of lithium prescriptions, including discontinuation, continuation and dosage. Maternal characteristics were defined for lithium non-users and users, and between those who continued and discontinued use. RESULTS:From 1995 to 2018, the prevalence of lithium prescribing per 10 000 pregnancies was 3.02 (95% CI: 2.64, 3.44) before pregnancy, 1.89 (95% CI: 1.59, 2.23) during pregnancy and 2.81 (95% CI: 2.44, 3.21) postpartum. Prescribing during pregnancy was low across the study period, with the most recent prevalence in 2018 of 1.03 (95% CI: 0.26, 4.11) per 10 000 pregnancies. Among 337 pregnancies with perinatal lithium prescribing, 48.4% involved a diagnosis of bipolar disorder. Of 227 pregnancies where lithium was prescribed preconception, 15.4% continued treatment throughout pregnancy; discontinuation occurred before pregnancy in 20.7%, and during second or third trimester in 30.8%; 33.0% followed other prescribing patterns. Women who discontinued lithium were more likely to be younger, have a body mass index ≥30 kg/m2, a diagnosis of bipolar disorder, a history of smoking and >10 primary care consultations in the 12 months preconception, compared with those who continued treatment. CONCLUSIONS:Lithium prescribing during pregnancy in the UK is uncommon and discontinuation is frequent, particularly in the later stages of pregnancy. These findings highlight the need for proactive perinatal mental healthcare strategies and close clinical monitoring, to reduce unintentional first-trimester exposure while ensuring continuity of care for maternal mental health.

The primary aim of this study was to compare the common reasons for hospitalization among adults with and without intellectual and developmental disabilities (IDD) in the United States. We examined hospitalizations for adults with and without IDD using the 2017 to 2019 National Inpatient Sample. Adults with IDD were matched to a sample without IDD, stratified by age (18-49 vs. ≥50), and compared for reasons for hospital admission and outcome differences. Adults with IDD, especially those 18 to 49, were frequently hospitalized for schizophrenia, while septicemia was the primary cause for those ≥50. Epilepsy was common among individuals with IDD and associated with higher healthcare costs and utilization. Those with IDD had more chronic conditions, longer stays, and higher postdischarge care needs. Enhancing community-based services and training a healthcare workforce focused on the specific needs of individuals with IDD can help reduce these disparities.

The transition to adult healthcare is a vulnerable time for individuals with autism spectrum disorder (ASD). Prior research using Medicaid data (2001–2005) found this group had declining utilization rates into adulthood for some types of care (e.g., psychiatric outpatient). Substantial changes to Medicaid and the ASD population have occurred since this time. We reassessed healthcare resource utilization (HCRU) across the transition to adulthood Medicaid claims data from 2015 to 2019. We selected enrollees with at least one fee for service claim, aged 16–19 years in 2015, who were also enrolled in 2019 using diagnostic groupings: ASD/no ID (n = 23,460), ID/no ASD (n = 21,256) and ASD + ID (n = 10,115). HCRU indicators included utilization rates and per capita expenditures for outpatient, inpatient, long-term, and medication care, with each type further divided into psychiatric and non-psychiatric (i.e., medical). The ID groups had overall higher HCRU than the ASD only group. ASD + ID adults had especially high HCRU for psychiatric outpatient care. HCRU increased into adulthood for psychiatric outpatient and long-term care, driven by higher expenditures among those with >0 expenditures. HCRU declined into adulthood for inpatient care and medication use. In contrast to 2001–2005, having an ID diagnosis resulted in greater HRCU across transition to adulthood, potentially reflecting changes in the Medicaid ASD population over time. Consistent with 2001–2005, utilization rates generally declined for all three groups across the transition to adulthood. Greater expenditure among those using psychiatric outpatient and long-term care in adulthood resulted in greater overall resource utilization than adolescence.

Objective: The objectives of this study were to, 1) estimate U.S. national rates of mental health hospitalization (MHH) and all-cause readmission, and 2) explore characteristics associated with readmissions for autistic and non-autistic adults. Methods: This study used the National Readmission Database (NRD) 2019 to examine 30-day all-cause readmissions following MHH in adults with autism, intellectual disability, ADHD, and mental health conditions. Analysis estimated rates of MHH by group, rates and odds of readmission, and factors associated with readmission. Results: More than one-third (36 %) of all admissions for autistic adults in 2019 were MHH, with schizophrenia the most common reason. Of all MHH index events in autistic adults, 17 % had a 30-day all-cause readmission. Readmissions were more common in autistic adults with ID (25 %) than in autistic adults without ID (15 %). Readmission was also slightly more common in female autistic adults (20 %) than male autistic adults (16 %), and autistic females had greater odds of readmission (OR 1.30, 95 % CI 1.09, 1.55) than autistic males, which was not true in non-autistic adults. Initial admission for schizophrenia was associated with increased odds of readmission for all groups (OR 1.37, 95 % CI 1.32, 1.42). Conclusions: The complexity of mental health conditions and their care in autistic adults underscores the urgent need for accessible and tailored mental health care services. Addressing these challenges will require collaborative efforts across healthcare sectors to create comprehensive, inclusive, and person-centered approaches to mental health care delivery for autistic adults across often disjointed service sectors.

This study explores how adults with autism exercise choice and control. Using the 2018-2019 National Core Indicator-In-Person Survey, it compares choices in life and everyday decisions between adults with autism and those with other developmental disabilities (DD) receiving services and examines differences across race/ethnicity within adults with autism. Results showed that adults with autism had fewer life choices than adults with other DD. Hispanic adults with autism had less choice in daily schedules, free time, and spending money than non-Hispanic Whites. Non-Hispanic Black adults with autism also showed less choice in daily schedules and free time but reported having enough choices in these areas. The study highlights disparities among racial and ethnic minorities, underscoring the need for culturally sensitive and inclusive support strategies.

BACKGROUND AND OBJECTIVES Ongoing systems-level changes aim to better identify and remedy the unmet health care needs of children with medical complexity (CMC). In tandem, home- and community-based services are expanding to support autistic children and their families. Despite the potential for overlap, CMC and autistic children are treated independently in services, research, and policy. We estimated the overlapping prevalence of CMC and autism among US children and health care expenditures for autistic CMC in comparison with other children. METHODS We analyzed 2 national cross-sectional surveys: the National Survey of Children’s Health (NSCH; 2017–2018, 2019–2022, and 2021–2022) and the Medical Expenditures Panel Survey (MEPS; combined 2010–2021), selecting for children aged 0 to 17 years. CMC were defined using 2 different algorithms varying in stringency. RESULTS In the most recent 2021 to 2022 NSCH (n = 103 748), the prevalence of CMC among autistic children was 59.28% (95% CI, 55.61%–62.84%) using one algorithm and 17.56% (95% CI, 14.41%–21.24%) using the more stringent algorithm. Forty-one percent of CMC were autistic using either algorithm. In the MEPS data (n = 55 637), autistic CMC had significantly greater median health care expenditures compared with other CMC and other autistic children. CONCLUSIONS There is extensive overlap of CMC and autism among children in the United States. When medical complexity and autism are both evident, expenditures are significantly higher than for either category alone. Despite this overlap and the associated high need, CMC and autism are generally treated as separate groups in services, research, and policy. These findings underscore the importance of cohesively understanding service needs across CMC, autistic children, and their caretakers.

INTRODUCTION:Postpartum readmission and severe maternal morbidity have been increasing in recent years in the U.S., but little is known about the risk of either for people with intellectual and developmental disabilities, including the autism spectrum. The purpose of the study is to establish an estimate of postpartum readmission in a nationally representative sample of people with intellectual and developmental disabilities. METHODS:This study used the National Readmission Database to examine the deliveries in people with intellectual and developmental disabilities (n=5,721), people on the autism spectrum (n=1,099), and people without intellectual and developmental disabilities or autism (n=3,890,553) in 2019 and 2020. Log-binomial regression was used to examine person and delivery characteristics associated with postpartum readmission in all deliveries. RESULTS:Postpartum readmission was more common in people with intellectual and developmental disabilities (6.6%) and people on the autism spectrum (3.3%) than in all other deliveries (1.5%). In adjusted analyses, people with intellectual and developmental disabilities (adjusted RR=3.50; 95% CI=3.15, 3.90) and people on the autism spectrum (adjusted RR=2.06; 95% CI=1.42, 2.97) had increased risk of postpartum readmission compared with people without these conditions. Other characteristics were also associated with increased risk of postpartum readmission, including 2.80 times the risk of postpartum readmission in people with severe maternal morbidity compared with that in those without (95% CI=2.66, 2.94). CONCLUSIONS:High rates of postpartum readmission in people with intellectual and developmental disabilities point to the need for a better understanding of the drivers of such high rates in these populations. These drivers could include population differences in co-occurring health and mental health conditions, social and community support, and accessible health care.

There is limited research on the prevalence of substance use disorders (SUDs) in autistic youth. Additionally, while mental health conditions and history of trauma have been associated with a higher prevalence of SUD in non-autistic youth, the research in autistic youth is scarce. Therefore, the purpose of this study was to examine the prevalence of SUDs in autistic youth compared to non-autistic youth with co-occurring mental health conditions and adverse childhood experiences. Data from 22,828 autistic youth and 601,348 non-autistic youth were drawn from the Child and Caregiver Linked Utilization and Outcomes Database (CCOULD). SUDs were identified using categorized ICD-10 diagnostic codes, and mental health comorbidities included six conditions (ADHD, anxiety, depression, bipolar disorder, schizophrenia/psychotic disorders, trauma/stress-related disorders), substantiated maltreatment allegations, and placement history. Overall prevalence of SUD was lower among autistic youth (1.7%) compared to non-autistic youth (3.8%, p < 0.001). Both mental health comorbidities and maltreatment allegations were significantly associated with having a SUD, regardless of autism diagnosis. Placement in out-of-home care significantly reduced the likelihood of SUD among non-autistic youth (UOR = 0.83, 95% CI: 0.80-0.87) but more than doubled the odds among autistic youth (UOR = 2.36, 95% CI: 1.88-2.97). While prevalence rates of SUDs are lower in autistic youth compared to non-autistic youth, the presence of co-occurring mental health conditions and adverse childhood experiences may increase SUD rates to a greater extent in autistic youth. Future research should further investigate the complex relationships among SUDs, adverse childhood experiences, and mental health conditions in autistic youth.

AbstractThe teratogenic potential of valproate in pregnancy is well established; however, evidence regarding the long-term safety of other antiseizure medications (ASMs) during pregnancy remains limited. Using routinely collected primary care data from the UK and nationwide Swedish registries to create a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in pregnancy, we show that those exposed to valproate were more likely to receive a diagnosis of autism, intellectual disability, and ADHD, when compared to children not exposed to ASMs. Additionally, children exposed to topiramate were 2.5 times more likely to be diagnosed with intellectual disability (95% CI: 1.23–4.98), and those exposed to carbamazepine were 1.25 times more likely to be diagnosed with autism (95% CI: 1.05–1.48) and 1.30 times more likely to be diagnosed with intellectual disability (95% CI: 1.01–1.69). There was little evidence that children exposed to lamotrigine in pregnancy were more likely to receive neurodevelopmental diagnoses. While further research is needed, these findings may support considering safer treatment alternatives well before conception when clinically appropriate.

Purpose We used data from the National Survey of Children's Health to (1) examine differences in economic hardship and safety net program use after the implementation of federal relief efforts, and (2) assess whether the COVID-19 pandemic exacerbated autism-based disparities in hardship and program use. Methods We examined five dimensions of economic hardship (poverty, food insecurity, medical hardship, medical costs, and foregone work) and four safety net programs (cash assistance, Supplemental Nutrition Assistance Program (SNAP), Special Supplemental Nutrition Program for Women, Infants and Children (WIC), and free or reduced-cost meals). First, we calculated adjusted prevalence and odds ratios to compare pre-COVID (2018-2019) and during COVID (2021) outcomes by autism status. Next, we calculated the adjusted odds of each outcome among autistic children compared to those of children with and without other special healthcare needs at both time points. Results COVID-19 exacerbated autism-based disparities in food insecurity, SNAP, and public health insurance, but alleviated inequities in medical hardship, foregone work, and cash assistance. Autistic children did not experience declines in food insecurity or increases in SNAP like other children; medical hardship and foregone work decreased more for autistic children; and the magnitude of autism-based differences in public coverage significantly increased during the pandemic. Conclusion Federal relief efforts likely improved economic outcomes of children; however, these effects varied according to type of hardship and by disability group. Efforts to promote economic well-being among autistic populations should be tailored to the financial challenges most salient to low-income autistic children, like food insecurity.

Mental health concerns are common in children with chronic health conditions, and concerns and treatment vary by race and ethnicity. This study used the National Survey of Children's Health 2019-2020 to examine the role of the medical home in addressing racial and ethnic disparities in access to mental health care. Our study identified racial and ethnic disparities in both medical home access and mental health care use among children and youth with special health care needs ages 6-17. These differences may be driven by different practice behaviors or preexisting levels of access to services by race and ethnicity.

Background Psychiatric comorbidities are common in patients with epilepsy. Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.Aim We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.Methods Using nationwide Swedish health registries, we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy. We then used summary data from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score regression. Finally, we assessed the potential bidirectional relationships using two-sample Mendelian randomisation.Results In a cohort of 7 628 495 individuals, we found that almost half of the 94 435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime (adjusted lifetime prevalence, 44.09%; 95% confidence interval (CI) 43.78% to 44.39%). We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric conditions. For example, we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder (rg=0.18, 95% CI 0.09 to 0.27, p<0.001)—a correlation that was more pronounced in focal epilepsy (rg=0.23, 95% CI 0.09 to 0.36, p<0.001). Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric conditions.Conclusions Psychiatric comorbidities are common in patients with epilepsy. Genetic correlations may partially explain some comorbidities; however, there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric conditions. These findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psychiatric comorbidities in epilepsy.

Higher education is an increasingly necessary achievement to attain employment. However, even in cases where a student has the academic skills to succeed, educational environments may not support students across all other domains necessary for education success, including social and communication needs. This is especially true for students with disabilities and autistic students, where the rate of completion of non-compulsory education is unknown. We used the Stockholm Youth Cohort (children aged 0-17 years from 2001 to 2011), a total population cohort (N = 736,180) including 3,918 autistic individuals, to investigate the association between autism without intellectual disability and completion of upper secondary education. We assessed the impact of sex and co-occurring Attention-Deficit/Hyperactivity Disorder (ADHD) on this association. By age 20 years (the expected age of completion), 68% of autistic students and 91% of non-autistic students admitted to upper secondary education had completed. In logistic regression models adjusted for student demographics, autistic students had almost five-fold higher odds of not completing secondary school (OR 4.90, 95% CI 4.56 5.26) compared to their non-autistic peers. Autistic students with ADHD had particularly high odds of non-completion of upper secondary school. Autistic students without intellectual disability attending mainstream education are substantially less likely to complete upper secondary education as compared to their peers. These findings have implications for the appraisal of how inclusive school policies serve autistic students' academic and social needs, ultimately addressing population health and independent living.

Emerging research suggests people with intellectual and developmental disabilities (IDD) have fertility rates similar to the general population. However, studies have highlighted riskier delivery outcomes, including premature delivery and cesarean section, in this group. The objective of this study was to establish prevalence of adverse delivery outcomes, including hospital readmission, in people with autism, other IDDs, and without autism or IDD. We used the National Readmission Database (NRD), an all-payer collection of inpatient hospital records, from 2019 and 2020 to examine deliveries. NRD (from the Healthcare Cost and Utilization Project) is sampled from 97% of all hospital discharges in the U.S. We compared people with autism, other IDD, and all other deliveries along antepartum (gestational diabetes), intrapartum (mode of delivery (vaginal, assisted vaginal, cesarean), hemorrhage, preeclampsia and eclampsia), and postpartum (prolonged hospital stay during delivery, readmission within 7 and 30 days of discharge) outcomes. We also examined patient characteristics including Medicaid insurance. Some outcomes were more common in people with autism and IDD, including preeclampsia (12% autism, 14% IDD, 7% other), instrumental delivery (39% autism, 47% IDD, 36% other), and stays longer than 5 days (7% autism, 9% IDD, 3% other). All-cause readmission within 30 days was also more common (3% autism, 6% IDD, 1% other). There was no difference in rate of cesarean section. Medicaid coverage was common in autistic people (59%) and people with IDD (52%), compared to 41% of other deliveries. This study highlights disparities in delivery outcomes of a demographic that is largely missing from pregnancy care and research. These disparities are likely further exacerbated by other social determinants of health, including race and ethnicity. Individual and structural factors including patient, clinician, and health system factors are all at play and need to be examined to better understand and adapt care delivery to this population.

The COVID-19 pandemic and subsequent mitigation efforts impacted communities in many ways and placed immense strain on the health care system, impacting access to services. The purpose of this study was to examine changes in prevalence of child health care, child health, and caregiver and household health within children with autism and children with special health care needs (CSHCN) pre-pandemic to early pandemic years. We examined data from the National Survey of Children’s Health to examine changes in child health care, child health, and caregiver and household health for autistic children and CSHCN from 2018 to 2021. About one-third of children with autism and CSHCN missed preventive checkups due to the COVID-19 pandemic and half had virtual care in 2021. Parents of children with autism had less help with care coordination in 2020 compared to previous years. In CSHCN prevalence of anxiety increased from 2018/2019 to 2021, with a concurrent increase in need for mental health care, this was not seen in children with autism. Finally, difficulty paying medical bills and for food was less common in 2020 and 2021 (compared to 2018/2019). The COVID-19 pandemic changed the healthcare landscape for everyone, including children with autism and CSHCN as highlighted in this study. Understanding the disruptions and how they impacted populations differently can be helpful in informing plans long-term emergency preparedness. This planning should involve disability inclusive policies, to ensure the most vulnerable groups retain health care access as needed. The COVID-19 pandemic impacted physical health, mental health, and access to health care for children with special health care needs. The specific impact of the pandemic on autistic children and their families is not thoroughly documented. What this study adds: Children with autism experienced disruptions to health care during the COVID-19 pandemic. As a group with great health care and service needs, disruptions could be overly impactful to health trajectories, strengthening the need for continuous, accessible care.

ImportanceSmall, geographically limited studies report that people with intellectual and developmental disabilities (IDD) have increased risk for serious pregnancy-related and birth-related challenges, including preeclampsia, preterm birth, and increased anxiety and depression, than their peers. United States–based population-level data among people with IDD are lacking.ObjectivesTo identify perinatal and postpartum outcomes among a national, longitudinal sample of people with IDD enrolled in public health insurance, compare subgroups of people with IDD, and compare outcomes among people with IDD with those of peers without IDD.Design, Setting, and ParticipantsThis retrospective cohort study used national Medicaid claims from January 1, 2008, to December 31, 2019, for 55 440 birthing people with IDD and a random sample of 438 557 birthing people without IDD. Medicaid funds almost half of all births and is the largest behavioral health insurer in the US, covering a robust array of services for people with IDD. Statistical analysis was performed from July 2023 to June 2024.ExposurePeople who had a documented birth in Medicaid during the study years.Main Outcome and MeasuresPerinatal outcomes were compared across groups using univariate and multivariate logistic regression. The probability of postpartum anxiety and depression was estimated using Kaplan-Meier and Cox proportional hazards regression.ResultsThe study sample included 55 440 birthing people with IDD (including 41 854 with intellectual disabilities [ID] and 13 586 with autism; mean [SD] age at first delivery, 24.9 [6.7] years) and a random sample of 438 557 birthing people without IDD (mean [SD] age at first delivery, 26.4 [6.3] years). People with IDD were younger at first observed delivery, had a lower prevalence of live births (66.6% vs 76.7%), and higher rates of obstetric conditions (gestational diabetes, 10.3% vs 9.9%; gestational hypertension, 8.7% vs 6.1%; preeclampsia, 6.1% vs 4.4%) and co-occurring physical conditions (heart failure, 1.4% vs 0.4%; hyperlipidemia, 5.3% vs 1.7%; ischemic heart disease, 1.5% vs 0.4%; obesity, 16.3% vs 7.4%) and mental health conditions (anxiety disorders, 27.9% vs 6.5%; depressive disorders, 32.1% vs 7.5%; posttraumatic stress disorder, 9.5% vs 1.2%) than people without IDD. The probability of postpartum anxiety (adjusted hazard ratio [AHR], 3.2 [95% CI, 2.9-3.4]) and postpartum depression (AHR, 2.4 [95% CI, 2.3-2.6]) was significantly higher among autistic people compared with people with ID only and people without IDD.Conclusions and RelevanceIn this retrospective cohort study, people with IDD had a younger mean age at first delivery, had lower prevalence of live births, and had poor obstetric, mental health, and medical outcomes compared with people without IDD, pointing toward a need for clinician training and timely delivery of maternal health care. Results highlight needed reproductive health education, increasing clinician knowledge, and expanding Medicaid to ensure access to care for people with IDD.

BackgroundAntiseizure medications (ASMs) during the first trimester of pregnancy have been associated with an increased risk of miscarriage.MethodsWe carried out a population-based cohort study using routinely collected healthcare data from the UK, 1995–2018. Pregnancies were identified in the Clinical Practice Research Datalink and we estimated the HR of miscarriage associated with prescriptions of ASMs during the first trimester of pregnancy, using Cox regression, adjusting for potential confounders, including ASM indications.ResultsASMs were prescribed during the first trimester in 7832 (0.8%) of 1 023 787 included pregnancies. 14.5% of pregnancies with first-trimester exposure to ASMs ended in miscarriage, while 12.2% without ASM exposure in the first trimester ended in miscarriage; after adjustment, there was a 1.06-fold relative hazard of miscarriage (95% CI 1.00 to 1.13) in women with first-trimester ASM use. After restricting to women with specific ASM indications, this association was not evident in women with epilepsy (adjusted HR 0.98, 95% CI 0.89 to 1.08), but was observed in women with bipolar or other psychiatric conditions (1.08, 95% CI 1.00 to 1.16) although CIs overlapped. Compared with discontinuation of ASMs prior to pregnancy, there was no evidence of increased risk of miscarriage for first-trimester ASM use in women with bipolar or other psychiatric conditions (1.02, 95% CI 0.87 to 1.20).ConclusionWe found no clear evidence to suggest that first-trimester ASM use increased the risk of miscarriage. Taken together, our analyses suggest that apparent associations between first-trimester ASM use and miscarriage may be the result of confounding by the presence of a bipolar disorder or associated unmeasured variables.

PURPOSE:Estimating causal effects in observational pharmacoepidemiology is a challenging task, as it is often plagued by confounding by indication. Restricting the sample to those with an indication for drug use is a commonly performed procedure; indication-based sampling ensures that the exposed and unexposed are exchangeable on the indication-limiting the potential for confounding by indication. However, indication-based sampling has received little scrutiny, despite the hazards of exposure-related covariate control.METHODS:Using simulations of varying levels of confounding and applied examples we describe bias amplification under indication-based sampling.RESULTS:We demonstrate that indication-based sampling in the presence of unobserved confounding can give rise to bias amplification, a self-inflicted phenomenon where one inflates pre-existing bias through inappropriate covariate control. Additionally, we show that indication-based sampling generally leads to a greater net bias than alternative approaches, such as regression adjustment. Finally, we expand on how bias amplification should be reasoned about when distinct clinically relevant effects on the outcome among those with an indication exist (effect-heterogeneity).CONCLUSION:We conclude that studies using indication-based sampling should have robust justification - and that it should by no means be considered unbiased to adopt such approaches. As such, we suggest that future observational studies stay wary of bias amplification when considering drug indications.