OBJECTIVE To evaluate whether prenatal exposure to specific antiseizure drugs increases the risk of neurodevelopmental disorders in children. DESIGN Population based cohort study. SETTING Healthcare use data from publicly and commercially insured beneficiaries in the United States, 2000-21. PARTICIPANTS Pregnant patients with epilepsy linked to offspring. INTERVENTIONS Dispensing of the antiseizure drug of interest during the second half of pregnancy (synaptogenesis period): carbamazepine, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, valproate, and zonisamide. The reference group consisted of pregnant patients with diagnosed epilepsy, but no antiseizure drug dispensation from three months before pregnancy until delivery. MAIN OUTCOMES MEASURES Any neurodevelopmental disorder, attention deficit hyperactivity disorder, autism spectrum disorder, behavioral disorder, developmental coordination disorder, intellectual disability, learning difficulty, and speech or language disorder identified using validated algorithms. Hazard ratios were estimated using Cox proportional hazard models with propensity score overlap weighting to adjust for potential confounders. RESULTS The cohort included 8887 children who were prenatally unexposed. Exposed pregnancies ranged from 219 for lacosamide to 5261 for levetiracetam. Valproate and zonisamide showed associations with several outcomes (adjusted hazard ratio range 1.26-4.50), whereas levetiracetam and phenytoin were not associated with an increased risk of any outcome. Several drugs were associated with a two to fourfold risk increase for intellectual disability, but estimates were imprecise because of the small number of children with this disorder. Although no meaningful associations were found for topiramate and lamotrigine across most outcomes, there was a potential signal for intellectual disability (both drugs) and learning difficulty (topiramate only; hazard ratio 1.23 based on small numbers). Carbamazepine and oxcarbazepine showed a modest risk increase for attention deficit hyperactivity disorder and behavioral disorders (hazard ratio range 1.23-1.40). Results were robust across several sensitivity analyses, including using lamotrigine as an active comparator. CONCLUSIONS The findings strengthen the evidence for increased neurodevelopmental risks among children with prenatal valproate exposure and suggest the need for further evaluation of zonisamide. Signals for other antiseizure drugs, observed in the context of several comparisons and rare outcomes, require confirmation as data accumulate.

BACKGROUND:Increasingly, protocols have been developed to optimize obstetric anesthesia care. However, there is a paucity of data on adherence to these guidelines. The primary aims of this study were to utilize the Multicenter Perioperative Outcomes Group (MPOG) database to estimate (1) the rate of adherence to best practice guidelines for cesarean delivery (CD) (2) the association of case- and hospital-level factors with adherence, and (3) the percentage of variability in adherence attributable to the patient-, case-, and hospital-level factors. METHODS:We performed a multicenter, observational cohort study utilizing the MPOG database to review all CDs in women aged 15-44. Best practices were defined based on societal guidelines and included timely antibiotic administration, post-spinal SBP maintenance >90 mmHg, general anesthesia (GA) avoidance, prevention of perioperative hypothermia, use of low-dose neuraxial morphine, post-spinal vasopressor infusions, and spinal needles ≥ 25-gauge. Covariates of interest included patient-, case-, and hospital-level factors. RESULTS:We analyzed 289,047 CD cases in the MPOG database from 2015-2022. The following adherence outcomes were observed: timely antibiotic administration, 86.2% (99%CI: 86-86.3%); post-spinal SBP maintenance, 96.7% (99%CI: 96.6-96.8%); avoidance of GA, 97.0% (99%CI: 96.9-97.0%); prevention of perioperative hypothermia, 56.7% (99%CI: 56.5-56.9%); use of low-dose neuraxial morphine, 74.2% (99%CI: 74.0-74.5%); use of post-spinal vasopressor infusion, 55.4% (99%CI: 55.1-55.8%); and use of ≥ 25-gauge needle for spinal anesthesia, 89.0% (99%CI: 88.6-89.4%). Poorer adherence correlated with factors at the patient- (ASA Physical Status ≥ 4), case- (evening or overnight CD), and institution-level (absence of obstetric fellowship or "Center of Excellence" status). CONCLUSIONS:Among our large cohort of CD cases, overall adherence to guideline-supported best practices was variable, with post-spinal vasopressor infusions being the lowest and avoidance of GA being the highest. Targeted interventions addressing these factors may improve quality and promote more optimal care.

BACKGROUND:Medication safety studies in pregnancy typically focus on selected or composite outcomes (eg, any malformation) to test specific hypotheses or verify suspected safety signals, potentially overlooking or masking other clinically significant associations (eg, individual malformations or malformation types). OBJECTIVE:To conduct a comprehensive, systematic screening for potential teratogenic safety alerts associated with first-trimester exposure to individual antipsychotics, using a tree-based scan statistic (TBSS) approach for simultaneous evaluation of a broad range of specific malformations and malformation groupings. METHODS:Using a US-nationwide cohort of >4.2 million mother-child dyads (2000-2020), pregnancies with ≥1 first-trimester antipsychotic dispensing were compared with antipsychotic-unexposed pregnancies. Individual congenital malformations were identified via International Classification of Diseases codes, grouped into increasingly aggregated higher-level clinically related categories. Leveraging this hierarchical classification tree, TBSS was used to scan for associations with individual malformation codes and code categories while tightly controlling type 1 error. Confounding was adjusted for via propensity score fine-stratification, and relative risks (RRs) were estimated using an unconditional Poisson scan statistic. The p-values were used to prioritise alerts for further investigation, and follow-up analyses were conducted to refine the understanding of statistical alerts. FINDINGS:Exposed pregnancies ranged from 68 (fluphenazine) to 18 366 (prochlorperazine). Antipsychotic-exposed versus antipsychotic-unexposed women tended to be older and to have a higher comorbidity burden and more healthcare encounters. Alerts for an increased risk (with p<0.1) were observed for skin anomaly after haloperidol (RR=1.88) and polydactyly after ziprasidone (RR=3.06) exposure. Results were consistent in sensitivity analyses. The data in the two external data sources were too sparse to confirm a safety alert. CONCLUSIONS:TBSS identified two potential alerts previously unreported for prenatal antipsychotic exposure. Importantly, no alerts for severe or life-threatening malformations were detected. Findings from this screening-based approach, therefore, align with existing evidence suggesting that antipsychotics are unlikely to be major teratogens. CLINICAL IMPLICATIONS:The potential risk increase observed for some less-severe malformations and some antipsychotics needs to be weighed against the high potential for relapse and mental health deterioration following treatment discontinuation. While no consistent patterns suggesting a strong teratogenic effect have emerged thus far for newer antipsychotics, continued monitoring of these medications is important.

BACKGROUND:Glucagon-like peptide-1 receptor agonist (GLP-1RA) use has increased among women of reproductive age, but limited data exist on safety in pregnancy. OBJECTIVE:To estimate the risk for nonlive birth, abnormal fetal growth, and major congenital malformation (MCM) with GLP-1RA dispensing in early pregnancy. DESIGN:In an observational cohort of pregnant women aged 16 to 55 years with a GLP-1RA dispensation in the 90 days before the last menstrual period (LMP), a target trial with 2 treatment strategies was emulated: continuation of dispensing into the first trimester (≥1 further dispensation), or noncontinuation. SETTING:Merative MarketScan U.S. insurance claims data (2011 to 2024). PARTICIPANTS:3572 pregnancies (41.1% [n = 1467] among women with type 2 diabetes). MEASUREMENTS:Risk for nonlive birth was estimated using a weighted Kaplan-Meier estimator. Among live-birth pregnancies linked to infants, the weighted prevalence of MCM, small for gestational age (SGA), and large for gestational age (LGA) was estimated. RESULTS:The weighted risk for nonlive birth was 29.7% with continuation and 27.1% with noncontinuation (adjusted risk ratio, 1.09 [95% CI, 0.98 to 1.23]). Among 2529 live-birth pregnancies, 1443 (57.1%) received at least 1 GLP-1RA dispensation after LMP and 1499 (829 continuers) were linked to an infant. Weighted prevalence ratios for continuation versus noncontinuation were 1.29 (CI, 0.82 to 2.06) for SGA, 1.08 (CI, 0.84 to 1.40) for LGA, and 1.21 (CI, 0.83 to 1.82) for MCM. LIMITATION:Potential residual confounding by prior glycemic control. CONCLUSION:Risks for nonlive birth, SGA, LGA, and MCM were not definitively higher with continuation of GLP-1RAs into early pregnancy. However, estimates for MCM and SGA were imprecise and were compatible with both no increased risk and clinically relevant differences in risk. PRIMARY FUNDING SOURCE:National Institutes of Health.

Background:Epic Cosmos is a relatively new centralized electronic health record dataset with high potential utility in perinatal epidemiologic research. Objectives:The study objectives were to develop replicable steps to create longitudinal, linked maternal-infant cohorts in Cosmos, assess completeness of key variables, evaluate potential selection bias with restrictions for longitudinal healthcare encounters, and provide an example epidemiologic analysis. Methods:We created maternal-infant cohorts by starting with live births during 2023-2024 recorded in the BirthFact data table and joining with additional data tables as needed. We selected and created variables for perinatal characteristics, common comorbidities, and routinely measured vital signs and laboratory values, and assessed variable completeness. We sequentially restricted the birth cohort for maternal-infant linkage and longitudinal healthcare from first-trimester prenatal care encounter through infant follow-up care within 12 weeks post-discharge from birth hospitalization. Finally, we conducted an example analysis of the association between high systolic blood pressure in the first trimester (≥140 mm Hg) and later onset of preeclampsia among those with chronic hypertension. Results:The total linked birth cohort included 2,624,186 pregnancies. Completeness was >90% for most variables assessed but was 77% for racial and ethnic group and 76% for body mass index at delivery. Characteristics of the cohort were similar to those reported for the entire United States birth population based on birth certificate data, including similar regional and racial-ethnic composition. Longitudinal cohort restriction requiring linked records from first trimester prenatal care through infant follow-up care reduced the cohort size to 509,148 pregnancies. However, restriction had minimal effects on cohort characteristics. In the example analysis, high systolic blood pressure was associated with increased risk of preeclampsia among those with chronic hypertension (aRR: 1.26; 95% CI: 1.22, 1.30). Conclusions:This study provides a rigorous and reproducible approach to creating longitudinal, linked maternal-infant cohorts in Epic Cosmos and the analytical findings suggest high data quality and representativeness.

This cohort study examines racial and ethnic disparities in retention in buprenorphine and methadone treatment among pregnant females with opioid use disorder (OUD) in the US.

OBJECTIVE:Evidence related to anemia in early pregnancy, and its resolution or persistence by late pregnancy, is limited. We evaluated pregnancy outcomes associated with anemia in early pregnancy and resolution compared with persistence in late pregnancy. METHODS:We used the Merative™ Marketscan ® Commercial Database of nationwide insurance claims (2018-2023) and included pregnant individuals without hereditary anemias. We used hemoglobin and hematocrit to identify anemia in early pregnancy (before 14 weeks of gestation) and late pregnancy (at or after 24 weeks of gestation). Pregnancy outcomes included preeclampsia, placenta previa, placental abruption, severe postpartum hemorrhage, blood products transfusion, cesarean birth, nontransfusion severe maternal morbidity (SMM), spontaneous preterm birth, medically indicated preterm birth, and small-for-gestational-age (SGA) birth weight. We used modified Poisson regression to estimate associations between: 1) anemia in early pregnancy and pregnancy outcomes; and 2) anemia resolution by late pregnancy and pregnancy outcomes, adjusting for confounders by inverse probability weighting. RESULTS:Among 73,586 individuals, 4.4% (95% CI, 4.3-4.6%) had anemia in early pregnancy. Early pregnancy anemia was associated with higher risk of each outcome assessed, with the exception of placenta previa, with the highest associated risk of blood products transfusion (2.4% vs 0.8%; adjusted risk ratio [aRR] 2.45; 95% CI, 1.91-3.13). Of those with early pregnancy anemia and laboratory values in late pregnancy (72.1%), 53.4% had persistent anemia and 46.6% had resolved anemia. Persistent anemia was associated with nontransfusion SMM (2.6% vs 1.1%, aRR 1.64; 95% CI, 1.13-2.37), blood products transfusion (2.9% vs 0.8%, aRR 2.60; 95% CI, 1.84-3.69), and SGA birth weight (8.5% vs 6.8%, aRR 1.23; 95% CI, 1.01-1.50), compared with those without anemia in the first trimester. The resolution of anemia by late pregnancy was not associated with nontransfusion SMM (1.6% vs 1.1%; aRR 1.07; 95% CI, 0.65-1.74) but was associated with blood products transfusion (1.6% vs 0.8%; aRR 1.64; 95% CI, 1.01-2.67) and SGA birth weight (10.0% vs 6.8%; aRR 1.38; 95% CI, 1.15-1.67) compared with those without anemia in the first trimester. CONCLUSION:Anemia in the first trimester was associated with adverse maternal and neonatal outcomes. The resolution of anemia by late pregnancy eliminated the association with nontransfusion SMM but not other outcomes, emphasizing the importance of treating anemia in early pregnancy and before pregnancy.

Anemia increases the risk of adverse perinatal outcomes, yet prevalence estimates in the United States are limited by selective samples or low sensitivity of diagnosis codes. We assessed the prevalence of anemia during pregnancy by analyzing hemoglobin and hematocrit values using trimester-specific standards in a longitudinal nationwide cohort of commercially insured individuals who gave birth from 2018 to 2023. We included individuals with laboratory values measured during routine screening (4 weeks to less than 14 weeks of gestation and 22 weeks to less than 30 weeks of gestation). The prevalence of anemia during pregnancy was 25.6% (95% CI, 25.3-25.9%). At prenatal care initiation (4 weeks to less than 14 weeks of gestation) and mid-pregnancy (22 weeks to less than 30 weeks of gestation) measurements, 4.3% (95% CI, 4.1-4.4%) and 24.5% (95% CI, 24.2-24.8%) of individuals had anemia, respectively. These findings demonstrate anemia during pregnancy is a public and population health issue.

Abstract While medication use is common among pregnant women, medication safety remains insufficiently characterized because studies in pregnant women are challenging due to safety concerns. The recent digitization of healthcare databases and advances in computational methods have created new opportunities for large-scale, retrospective drug safety evaluations. Here, we present PregMedNet, a platform that characterizes multifaceted maternal medication associations on neonatal outcomes during pregnancy, covering more than 27,000 drug-disease pairs across 1,152 medications and 24 outcomes. These results encompass known and additional odds ratios (ORs), adjusted ORs, and drug-drug interactions, systematically analyzed using nationwide claims data and an advanced machine learning pipeline. Notably, one of the associations identified in this study is supported by in vivo experiments, increasing confidence in PregMedNet’s findings and highlighting the utility of claims data and machine learning for perinatal medication safety studies. Additionally, potential biological mechanisms underlying the associations are explored using a graph learning method, providing candidate pathways for future mechanistic investigations. We expect that PregMedNet will contribute to advancing maternal medication safety and improving neonatal outcomes by providing extensive, multifaceted drug safety information on this previously underrepresented population.

AIM:Congenital malformations are important outcomes when evaluating medication safety in pregnancy. However, the accuracy of claims-based algorithms for identifying organ-specific malformations remains understudied. We validated algorithms for four malformation groups: urinary tract, genital, gastrointestinal, and musculoskeletal. MATERIALS AND METHODS:Using the Mass General Brigham (MGB, 2007-2020) and Stanford Medicine (2016-2023) databases, we identified infants with potential malformations of interest based on diagnosis and procedure codes within 90 days of birth. A total of 150 cases were sampled for each malformation group. Positive predictive values (PPV) were estimated to quantify the validity of the algorithms, separately by site and by International Classification of Diseases (ICD) coding system. RESULTS:For MGB ICD-9, MGB ICD-10, and Stanford ICD-10 algorithms, respectively, PPVs were 100%, 98.0%, and 95.8% for urinary tract malformations; 98.0%, 95.9%, and 93.8% for genital malformations; 76.0%, 78.0%, and 76.0% for gastrointestinal malformations; and 85.4%, 84.0%, and 62.0% for musculoskeletal malformations. False positives were primarily attributed to suspected malformations that were later ruled out and to broader or inaccurate coding for diagnoses that were not major malformations. CONCLUSIONS:Claims-based algorithms demonstrated high PPVs for urinary tract and genital malformations and moderate for gastrointestinal malformations, but there was variation in musculoskeletal PPVs between the institutions with different patient populations.

OBJECTIVE:The primary objective of this study was to estimate the prevalence of new-onset anxiety diagnoses in the postpartum period. We also aimed to estimate the prevalence of psychiatric comorbidities, explore changes by year, and identify risk factors for new-onset postpartum anxiety. METHODS:This retrospective cohort study used the Merative™ MarketScan ® Commercial Database and included adult women with commercial insurance who were at least 18 years of age, delivered a singleton or multiple gestation between 2008 and 2021, and did not have a preexisting or prepregnancy diagnosis of depression, anxiety, or posttraumatic stress disorder (PTSD). The primary outcome was a new-onset anxiety diagnosis, based on International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes, during the postpartum period (up to 12 months after childbirth). Secondary outcomes were comorbid anxiety with depression and PTSD. We also estimated the prevalence of each psychiatric condition by year and identified risk factors associated with postpartum anxiety. Univariable and multivariable regression models were constructed to identify risk factors. RESULTS:From the 1,469,121 individuals identified without prenatal mental health disorders, 84,984 individuals (5.8%; 95% CI, 5.7-5.8%) were diagnosed with new-onset postpartum anxiety within 12 months of childbirth, with 9,490 diagnosed in the first month and 75,494 diagnosed between 1 month and 1 year postpartum. Comorbid anxiety and depression occurred in 18.0 per 1,000 individuals in the study cohort (95% CI, 17.8-18.2), and comorbid anxiety and PTSD occurred in 0.9 per 1,000 individuals (95% CI, 0.9-1.0). The prevalence of postpartum anxiety increased from 30.8 per 1,000 individuals in 2008 to 122.9 per 1,000 individuals in 2021 ( P for trend<.001). Independent risk factors for new-onset postpartum anxiety diagnosed 1-12 months postpartum included younger age, North Central U.S. residence, earlier gestational age at delivery, cesarean delivery, antenatal or early postpartum sleep disorders, severe maternal morbidity (including transfusion), neglected medical conditions, and neonatal complications. CONCLUSION:Postpartum anxiety was estimated to affect nearly 6% of patients with commercial insurance in the United States and has increased fourfold since 2008. Risk factors associated with postpartum anxiety may help to identify at-risk individuals who could benefit from early intervention.

Importance:Sleep disturbances are common in pregnancy and often treated with nonbenzodiazepine sedative hypnotics (Z-drugs). However, there is limited evidence on the fetal safety of Z-drugs. Objective:To evaluate whether Z-drug exposure in the first trimester of pregnancy is associated with an increased risk of congenital malformations. Design, Setting, and Participants:This US population-based cohort study evaluated health care utilization data from publicly insured beneficiaries in the Medicaid database (2000-2018) and commercially insured beneficiaries in the Merative MarketScan database (2003-2020). Participants were pregnant individuals and their liveborn infants, with maternal enrollment from 90 days before pregnancy to 30 days after delivery and infant enrollment for 90 days after birth unless death occurred sooner. Data analysis was performed from November 2023 to April 2025. Exposure:At least 1 dispensing of Z-drugs (zaleplon, eszopiclone, or zolpidem) in the first trimester of pregnancy compared with no dispensing. Main Outcomes and Measures:Major congenital malformations were identified using linked maternal and infant claims. The risks of any major congenital malformation, organ-specific malformations, and individual malformations in pregnancies with Z-drug exposure in the first trimester were compared with the risks in unexposed pregnancies. Relative risks (RRs) and 95% CIs were estimated. Propensity score fine stratification weights were used to control for confounders. Results:A total of 4 281 579 pregnancies were identified (mean [SD] maternal age at delivery, 25.2 [6.0] years in Medicaid and 31.6 [4.6] years in MarketScan). First-trimester Z-drug exposure was identified in 11 652 (0.5%) of 2 506 106 pregnancies in Medicaid and 10 862 (0.6%) of 1 775 473 pregnancies in MarketScan; 92.1% of exposed pregnancies had zolpidem exposure. The adjusted pooled RR for malformations overall was 1.01 (95% CI, 0.95-1.08). While adjusted pooled RRs were increased for abdominal wall defects (1.46; 95% CI, 0.89-2.38), tetralogy of Fallot (1.45; 95% CI, 0.86-2.46), and neural tube defects (1.62; 95% CI, 0.96-2.74), these associations were imprecisely estimated, driven by the Medicaid cohort and not replicated in the MarketScan cohort. Results were consistent across multiple sensitivity analyses. Conclusions and Relevance:These findings suggest that Z-drug exposure in the first trimester of pregnancy is not associated with a meaningful elevation in the risk of congenital malformations overall, nor was there a consistent signal observed for organ-specific or uncommon, individual malformations examined.

Objective To compare the incidence of neurodevelopmental disorders among children with prenatal exposure to buprenorphine versus methadone. Design Population based cohort study. Setting US nationwide Medicaid data on >2.5 million live births from 2000 to 2018. Participants 18 612 pregnancies exposed to buprenorphine or methadone, of which 587 were excluded from the analysis owing to exposure to the comparator drug. Main outcome measures The primary outcome was a composite of neurodevelopmental disorders (autism spectrum disorder, attention deficit/hyperactivity disorder, developmental speech or language disorder, developmental coordination disorder, behavioural disorder, learning difficulty, or intellectual disability). Individual neurodevelopmental disorders were considered secondary outcomes. Cumulative incidences were obtained using Kaplan-Meier analyses, and hazard ratios using Cox proportional hazards regression. Propensity score overlap weighting was applied to adjust for confounding, including personal characteristics, maternal medical and mental health comorbidities, exposure to medications and other substances, proxies for severity of opioid use disorder, healthcare utilisation, and adequacy of prenatal care utilisation. Results 12 635 children were exposed to buprenorphine and 5390 to methadone prenatally. The crude cumulative incidence of any neurodevelopmental disorder at age 8 years among those exposed to buprenorphine was 34% (95% confidence interval (CI) 30% to 38%) and among those exposed to methadone was 33% (29% to 37%). Adjusted analyses suggested slightly lower hazards of any neurodevelopmental disorder associated with exposure to buprenorphine versus methadone (adjusted hazard ratio 0.81, 95% CI 0.70 to 0.94). Similar results were obtained for the individual neurodevelopmental disorders such as attention deficit/hyperactivity disorder (0.89, 0.65 to 1.21) and autism spectrum disorder (0.74, 0.46 to 1.21). With prevalent use, prenatal exposure to buprenorphine was associated with lower hazards of any neurodevelopmental disorder compared with prenatal exposure to methadone (adjusted hazard ratio 0.62, 0.51 to 0.76). This association was not observed with treatment initiation during pregnancy (adjusted hazard ratio 1.13, 0.90 to 1.42). Further sensitivity analyses indicated results consistent with no increased risk of neurodevelopmental disorders among pregnancies exposed to buprenorphine versus methadone. Conclusions The findings of this study suggest no increased risk of long term adverse neurodevelopmental outcomes among children with prenatal exposure to buprenorphine versus methadone, further supporting buprenorphine as a safe treatment option for opioid use disorder during pregnancy.

Estimating effects of interventions is a central task in perioperative and critical care outcomes research. While randomized trials remain the accepted standard for causal inference, trial data are not always available to inform clinical decisions, and some questions cannot be answered feasibly or efficiently with trials. In these settings, studies using observational healthcare data may be used to inform practice. Causal inference from observational data has been reconsidered in recent years, challenging the prevailing notion among clinical researchers that causal conclusions cannot be drawn from observational studies. The "target trial framework" is one contribution within a growing methodologic field that helps investigators avoid common pitfalls in observational study design and analysis. Importantly, researchers must understand which biases this framework can-and cannot-help avoid. The authors present an overview of target trial emulation and describe the promise and limitations of this framework for improving observational perioperative and critical care outcomes research.

Introduction:Neuraxial analgesia is the most effective modality for pain relief during labor; yet utilization varies considerably among racial and ethnic groups in the United States-representing a health disparity. Little is known about how maternal and obstetric characteristics may contribute to these differences and whether variation exists among a larger number of racial and ethnic groups. The objective of our study was to evaluate differences in neuraxial labor analgesia use among racial and ethnic groups in the United States. Methods:We analyzed vital statistics data from in-hospital spontaneous vaginal births of singletons during 2016 to 2022 in the United States (N = 26,345,765). Race and Hispanic ethnicity were considered as social constructs, measured by self-report, and combined into seven racial and ethnic groups for analysis. The outcome of interest was neuraxial labor analgesia use. We conducted sequentially adjusted multivariable modified Poisson regression models to estimate relative risks (RRs) with 95% confidence intervals (CIs) for associations between racial and ethnic groups and neuraxial labor analgesia. We first adjusted for delivery year and maternal characteristics: age, body mass index, insurance status, and educational background. We then additionally adjusted for obstetric characteristics: timing of prenatal care initiation, gestational age at delivery, and obstetric history (prior live birth and prior cesarean birth). We further descriptively assessed variation in utilization among Asian, Native Hawaiian or Other Pacific Islander (NHOPI), and Hispanic subgroups. Results:The rate of neuraxial labor analgesia use was 74% among 15,373,550 spontaneous vaginal, singleton births in the United States. White individuals had the highest rate (78%), and NHOPI and American Indian and Alaska Native (AI/AN) individuals had the lowest rates (58% and 61%, respectively) of use. After adjustment for covariates, the RR of using neuraxial labor analgesia was lowest in NHOPI individuals (0.78; 95% CI, 0.77-0.79) and AI/AN individuals (0.82; 95% CI, 0.82-0.82) compared with White individuals. The fully adjusted RRs were 0.93 (95% CI, 0.93-0.93) for Hispanic individuals, 0.98 (95% CI, 0.98-0.98) for Asian individuals, 0.96 (95% CI, 0.96-0.96) for Black individuals, and 0.97 (95% CI, 0.97-0.98) for multiracial individuals. In a secondary analysis, utilization ranged from 70% to 82% among Asian subgroups, 60% to 69% among NHOPI subgroups, and 64% to 81% among Hispanic subgroups. Conclusions:Neuraxial labor analgesia use in the United States was lowest among NHOPI and AI/AN individuals, independent of measured maternal and obstetric characteristics. Efforts are needed to understand and address disparities in contemporary practice with a particular focus on healthcare access and NHOPI and AI/AN communities.

OBJECTIVE:Treatment of pregnant patients with opioid use disorder with methadone or buprenorphine is crucial for maternal and neonatal safety. While several clinical trials have demonstrated higher treatment discontinuation rates for buprenorphine compared with methadone outside of pregnancy, evidence during pregnancy and the postpartum period is limited. The authors compared treatment discontinuation between buprenorphine and methadone during pregnancy and over follow-up through 1 year postpartum. METHODS:This was a cohort study, using nationwide Medicaid data, of pregnant patients who initiated methadone or transmucosal buprenorphine (with or without naloxone) for opioid use disorder during the first trimester. The primary outcome was treatment discontinuation, defined as a treatment gap ≥60 days; alternative definitions for discontinuation were explored in sensitivity analyses. Hazard ratios were estimated using Cox proportional hazards regression with propensity score overlap weighting to control for confounding. Subgroup analyses were conducted, stratified by buprenorphine alone versus the buprenorphine/naloxone combination, each compared to methadone. RESULTS:Overall, 696 pregnant patients were identified who initiated methadone treatment and 1,538 who initiated buprenorphine treatment in the first trimester. Compared to methadone initiators, buprenorphine initiators were more likely to discontinue treatment during pregnancy (32.8% for buprenorphine vs. 25.6% for methadone; weighted hazard ratio=1.41, 95% CI=1.15, 1.72) and through 1 year postpartum (58.8% vs. 49.0%; hazard ratio=1.37, 95% CI=1.19, 1.57). For patients initiating the buprenorphine/naloxone combination, the hazard ratio was 1.73 (95% CI=1.36, 2.19) during pregnancy and 1.56 (95% CI=1.30, 1.86) through 1 year postpartum. For patients initiating buprenorphine alone, the hazard ratios were 1.14 (95% CI=0.90, 1.46) and 1.23 (95% CI=1.04, 1.46), respectively. Varying the treatment gap used to define discontinuation in sensitivity analyses yielded consistent results. CONCLUSION:Pregnant patients initiating transmucosal buprenorphine during early pregnancy were more likely to discontinue treatment than those initiating methadone, but treatment discontinuation was high for both treatments. The study findings highlight the importance of identifying and addressing barriers to treatment retention among pregnant patients with opioid use disorder.