Antihypertensive utilization patterns among pregnant persons with pre-existing hypertension in the US: A population-based study.

BACKGROUND: Hypertension among persons with childbearing potential is on the rise. Maintaining proper blood pressure during pregnancy is vital to prevent maternal and neonatal complications. Yet, limited evidence on the risk-benefit of various antihypertensives presents challenges for informed decision-making during this critical period. This study aimed to examine the utilization patterns of different classes of antihypertensives among persons with pre-existing hypertension before, during, and after pregnancy. METHODS: We used MarketScan® Commercial Database 2011-2020 to analyze antihypertensive utilization among pregnant persons aged 12 to 55 identified via a validated algorithm. Pre-existing hypertension was defined as ≥1 inpatient or ≥2 outpatient encounters for hypertension within the 180 days preceding the LMP. Antihypertensive utilization was described during target periods: 0-3 months (0-3M) before pregnancy, 1st/2nd/3rd trimester (T1/2/3), 0-3M, and 4-6M after pregnancy. RESULTS: We identified 1,950,292 pregnancies, of which 20,576 (12,978 live and 7,598 non-live) had pre-existing hypertension. Both groups had similar antihypertensive use (80.1% and 81.0%, respectively) during the 6 months before pregnancy (baseline). For live-birth pregnancies, 13.9% of baseline users discontinued treatment during pregnancy, while 28.9% of non-users initiated antihypertensives during pregnancy, and 17.2% started postpartum. Before pregnancy, the predominant antihypertensives included thiazide diuretics (21.9%), combined α- and ß-blockers (18.4%), and dihydropyridines (16.2%). During pregnancy, thiazide diuretics, cardioselective ß-blockers, and ACE inhibitors declined (T3: 3.0%, 4.2%, and 0.8%). Dihydropyridine use was steady during pregnancy, but preference shifted from amlodipine to nifedipine in T3 (2.2.% vs.10.8%). Central α2-agonists increased during pregnancy (up to 15.2% in T3) compared to both pre- (9.8%) and post-pregnancy (5.7%). ARBs mirrored ACE inhibitors, with less than 1% utilization in later trimesters. Combination agents dropped from 10.8% pre-pregnancy to 0.8% in T3, then rebounded to 7.3% post-pregnancy. CONCLUSION: Research is warranted to evaluate the choice of antihypertensives and optimal timing to switch to safer alternatives, considering maternal and fetal outcomes.

Antibiotic treatment to prevent pediatric acute otitis media infectious complications: A meta-analysis.

BACKGROUND: Most US children with acute otitis media [AOM] receive prompt antibiotic treatment, though guidelines encourage watchful waiting. Previous systematic reviews of antibiotics versus watchful waiting have focused on symptom resolution and RCTs, limiting the assessment of serious, rare complications. We sought to evaluate these complications by including observational studies. METHODS: RCTs and observational studies that compared antibiotics to placebo or watchful waiting for pediatric clinician diagnosed AOM were identified [PubMed/MEDLINE, Embase, Cochrane Database of Systematic Reviews, Central Register of Controlled Trials, and Web of Science] and reviewed for meta-analysis. Two reviewers independently extracted study characteristics, patient characteristics, and outcomes. We assessed publication bias, study bias with ROBINS-1 and RoB-2 and used random-effects models to assess treatment effects. RESULTS: 24 studies were included. Antibiotics decreased the risk of acute mastoiditis [incidence 0.02%, RR 0.48, 95% CI 0.40-0.59; NNT 5,368]. This protective effect may be underestimated because of misclassification of non-suppurative conditions as AOM. Intracranial complications remained too rare to assess. Antibiotics markedly increased the risk of adverse effects [incidence 10.5%, RR 1.49, 1.27-1.73; NNH 23]. Studies used non-specific criteria for acute mastoiditis, potentially underestimating treatment effects. CONCLUSIONS: Prompt antibiotic therapy reduces the risk for some AOM complications. The NNT to prevent serious, rare complications is high, while the NNH is relatively low. Large-scale population-based observational studies using real-world datasets with validated measures of severe complications are needed to improve understanding of risk factors for serious AOM complications, facilitate more selective antibiotic therapy, and optimize individual outcomes and public health.

Prenatal Exposure to Valproic Acid Across Various Indications for Use.

Importance: Teratogenic outcomes associated with valproic acid use represent a substantial concern for persons of childbearing age. Regulatory agencies worldwide have enhanced warnings or implemented risk minimization programs to reduce exposure during pregnancy. Objectives: To determine pregnancy rates during valproic acid use and concomitant contraception use across indications. Design, Setting, and Participants: This retrospective cohort study used data from the Merative MarketScan commercial claims databases from January 1, 2005, to December 31, 2020, to identify female patients aged 12 to 44 years who initiated valproic acid treatment and had continuous insurance enrollment 6 months before initiation and 9 months after treatment end. A treatment episode included consecutive prescription fills that occurred within 7 days from the end of the days' supply of the previous dispensing. Data were analyzed from March 1 to September 10, 2023. Main Outcomes and Measures: Treatment episodes were categorized by inferred indication using diagnoses preceding treatment initiation, including epilepsy, migraine or headache, mood disorders, and unknown or off-label uses. Pregnancy incidence rate ratios (IRRs) were calculated and were adjusted for age and calendar year. Contraceptive use (prescription contraceptives, intrauterine devices, and implants) during treatment was examined. Results: The cohort included 165 772 valproic acid treatment episodes among 69 390 women (mean [SD] age, 29.8 [10.0] years). Mood disorders (42.5%) were the most common indication, followed by migraine or headache (20.1%), with epilepsy playing a minor role (14.9%). Pregnancy incidence rates during valproic acid use remained unchanged, with a rate of 1.74 (95% CI, 1.14-2.53) per 100 person-years in 2005 and a rate of 1.90 (95% CI, 1.16-3.12) per 100 person-years in 2019. Compared with epilepsy, pregnancy rates were more than double for mood disorder (IRR, 2.16 [95% CI, 1.93-2.42]) and migraine or headache (IRR, 2.01 [95% CI, 1.92-2.09]). Few treatment episodes coincided with contraceptive use (37 012 [22.3%]), and oral dosage forms were the most common (27 069 [73.1%]). Conclusions and Relevance: In this cohort study of patients of childbearing age who used valproic acid, pregnancy rates during valproic acid use did not decrease despite enhanced US Food and Drug Administration safety communications, and contraception use remained low. Patients with migraine and mood disorders accounted for the largest proportion of valproic acid use and had the highest pregnancy rates, while patients with epilepsy had the lowest. These findings suggest a need to enhance efforts to mitigate prenatal exposure to valproic acid, especially for indications where the risk of use during pregnancy outweighs the benefit.

Prenatal Care Initiation and Exposure to Teratogenic Medications.

Importance: With new legal abortion restrictions, timing of prenatal care initiation is critical to allow for discussion of reproductive options among pregnancies exposed to teratogenic medications. Objective: To investigate the prevalence of prenatal exposure to teratogenic medications and prenatal care initiation across gestational weeks. Design, Setting, and Participants: This descriptive, population-based cross-sectional study used health encounter data from a national sample of individuals with employer-sponsored health insurance. A validated algorithm identified pregnancies among persons identifying as female that ended with a live or nonlive outcome between January 2017 and December 2019. Data were analyzed from December 2022 to December 2023. Exposures: Prenatal exposure to any of 137 teratogenic medications, measured via pharmacy and medical claims. Measurement of prenatal care initiation was adapted from the Children's Health Care Quality Measures. Main Outcomes and Measures: Prevalence of prenatal exposure to teratogens and prenatal care initiation by gestational week. Timing of prenatal teratogenic exposure was compared with timing of prenatal care initiation and legal abortion cutoffs. Results: Among 639 994 pregnancies, 472 472 (73.8%; 95% CI, 73.7%-73.9%) had a live delivery (mean [SD] age, 30.9 [5.4] years) and 167 522 (26.2%; 95% CI, 26.1%-26.3%) had a nonlive outcome (mean [SD] age, 31.6 [6.4] years). Of pregnancies with live deliveries, 5.8% (95% CI, 5.7%-5.8%) were exposed to teratogenic medications compared with 3.1% (95% CI, 3.0%-3.2%) with nonlive outcomes. Median time to prenatal care was 56 days (IQR, 44-70 days). By 6 weeks' gestation, 8186 pregnancies had been exposed to teratogenic medications (25.2% [95% CI, 24.7%-25.7%] of pregnancies exposed at any time during gestation; 1.3% [95% CI, 1.3%-1.3%] of all pregnancies); in 6877 (84.0%; 95% CI, 83.2%-84.8%), prenatal care was initiated after 6 weeks or not at all. By 15 weeks, teratogenic exposures had occurred for 48.9% (95% CI, 48.4%-49.5%) of all teratogen-exposed pregnancies (2.5% [2.4-2.5] of all pregnancies); prenatal care initiation occurred after 15 weeks for 1810 (16.8%; 95% CI, 16.1%-17.5%) with live deliveries and 2975 (58.3%; 95% CI, 56.9%-59.6%) with nonlive outcomes. Teratogenic medications most used within the first 15 gestational weeks among live deliveries included antiinfectives (eg, fluconazole), anticonvulsants (eg, valproate), antihypertensives (eg, lisinopril), and immunomodulators (eg, mycophenolate). For nonlive deliveries, most antihypertensives were replaced by vitamin A derivatives. Conclusions and Relevance: In this cross-sectional study, most exposures to teratogenic medications occurred in early pregnancy and before prenatal care initiation, precluding prenatal risk-benefit assessments. Prenatal care commonly occurred after strict legal abortion cutoffs, prohibiting consideration of pregnancy termination if concerns about teratogenic effects arose.

Common teratogenic medication exposures-a population-based study of pregnancies in the United States.

BACKGROUND: Risk mitigation for most teratogenic medications relies on risk communication via drug label, and prenatal exposures remain common. Information on the types of and risk factors for prenatal exposures to medications with teratogenic risk can guide strategies to reduce exposure. OBJECTIVE: This study aimed to identify medications with known or potential teratogenic risk commonly used during pregnancy among privately insured persons. STUDY DESIGN: We used the Merative™ MarketScan® Commercial Database to identify pregnancies with live or nonlive (ectopic pregnancies, spontaneous and elective abortions, stillbirths) outcomes among persons aged 12 to 55 years from 2011 to 2018. Start/end dates of medication exposure and pregnancy outcomes were identified via an adapted algorithm based on validation studies. We required continuous health plan enrollment from 90 days before conception until 30 days after the pregnancy end date. Medications with known or potential teratogenic risk were selected from TERIS (Teratogen Information System) and drug monographs based on the level of risk and quality of evidence (138 with known and 60 with potential risk). We defined prenatal exposure on the basis of ≥1 outpatient pharmacy claim or medical encounter for medication administration during target pregnancy periods considering medication risk profiles (eg, risk only in the first trimester or at a certain dose threshold). Sex hormones and hormone analogs, and abortion and postpartum/abortion hemorrhage treatments were not considered as teratogenic medications because of challenges in separating pregnancy-related indications, nor were opioids (because of complex risk-benefit considerations) or antiobesity medications if their only teratogenic mechanism was weight loss. RESULTS: Among all pregnancies, the 10 medications with known teratogenic risk and the highest prenatal exposures were sulfamethoxazole/trimethoprim (1988 per 100,000 pregnancy-years), high-dose fluconazole (1248), topiramate (351), lisinopril (144), warfarin (57), losartan (56), carbamazepine (50), valproate (49), vedolizumab (28 since 2015), and valsartan (25). Prevalence of exposure to sulfamethoxazole/trimethoprim decreased from 2346 to 1453 per 100,000 pregnancy-years from 2011 to 2018, but prevalence of exposure to vedolizumab increased 6-fold since its approval in 2015. Prenatal exposures in the first trimester were higher among nonlive pregnancies than among live-birth pregnancies, with the largest difference observed for warfarin (nonlive 370 vs live birth 78), followed by valproate (258 vs 86) and topiramate (1728 vs 674). Prenatal exposures to medications with potential teratogenic risk were most prevalent for low-dose fluconazole (6495), metoprolol (1325), and atenolol (448). The largest first-trimester exposure differences between nonlive and live-birth pregnancies were observed for lithium (242 vs 89), gabapentin (1639 vs 653), and duloxetine (1914 vs 860). Steady increases in hydralazine and gabapentin exposures were observed during the study years, whereas atenolol exposure decreased (561 to 280). CONCLUSION: Several medications with teratogenic risk for which there are potentially safer alternatives continue to be used during pregnancy. The fluctuating rates of prenatal exposure observed for select teratogenic medications suggest that regular reevaluation of risk mitigation strategies is needed. Future research focusing on understanding the clinical context of medication use is necessary to develop effective strategies for reducing exposures to medications with teratogenic risk during pregnancy.

Trends in Prescribing of Non-steroidal Anti-inflammatory Medications in the US Ambulatory Care Setting From 2006 to 2016.

While opioid prescribing has significantly decreased from a peak in 2012, less is known about the national utilization of non-opioid analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP) in the context of the opioid crisis. The objective of this study is to characterize the prescribing trends of NSAIDs and APAP in the US ambulatory care setting. We conducted repeated cross-sectional analyses using the 2006-2016 National Ambulatory Medical Care Survey. NSAID-involved visits were defined as patient visits among adults in which NSAIDs were ordered, supplied, administered, or continued. We used similarly-defined APAP visits as a referent group for context. After excluding aspirin and other NSAID/APAP combination products containing opioids, we calculated the annual proportion of NSAID-involved visits among all ambulatory visits. We conducted trend analyses using multivariable logistic regression adjusted for years, patient, and prescriber characteristics. From 2006 to 2016, there were 775.7 million NSAID-involved visits and 204.3 million APAP-involved visits. Most NSAIDs-involved visits were from patients aged 46-64 years (39.6%), female (60.4%), White (83.2%), and having commercial insurance (49.0%). There were significant increasing trends for the proportion of NSAID-involved visits (8.1-9.6%) and APAP-involved visits (1.7-2.9%) (both P < .0001). We observed an overall increase in NSAID and APAP-involved visits in US ambulatory care settings from 2006 to 2016. This trend may be attributed to decreasing opioid prescribing and raises safety concerns related to acute or chronic NSAID and APAP use. PERSPECTIVE: This study shows an overall increasing trend in NSAID use reported in nationally representative ambulatory care visits in the United States. This increase coincides with previously reported significant decreases in opioid analgesic use, particularly after 2012. Given the safety concerns related to chronic or acute NSAID use, there is a need to continue monitoring the use trends of this class of medication.

Protocol of a Combined Cohort and Cross-Sectional Study of Persons Receiving Medical Cannabis in Florida, USA: The Medical Marijuana and Me (M3) Study.

Significant knowledge gaps regarding the effectiveness and safety of medical cannabis (MC) create clinical challenges for MC physicians, making treatment recommendations and patients choosing treatment among the growing number of options offered in dispensaries. Additionally, data describing the characteristics of people who use MC and the products and doses they receive are lacking. The Medical Marijuana and Me (M3) Study was designed to collect patient-centered data from MC users. We aim to describe preferred MC use patterns that patients report as "most effective" for specific health conditions and symptoms, identify user characteristics associated with such use patterns, characterize adverse effects, including cannabis use disorder, identify products and patient characteristics associated with adverse effects, describe concurrent prescription medication use, and identify concomitant medication use with potential drug-MC interaction risk. Among MC initiators, we also aim to quantify MC use persistence and identify reasons for discontinuation, assess MC utilization pattern trajectories over time, describe outcome trajectories of primary reasons for MC use and determine factors associated with different trajectories, track changes in concomitant substance and medication use after MC initiation, and identify factors associated with such changes. M3 is a combined study comprised of: (1) a prospective cohort of MC initiators completing surveys at enrollment, 3 months, and 9 months after MC initiation and (2) a cross-sectional study of current MC users. A multidisciplinary committee including researchers, physicians, pharmacists, patients, and dispensary personnel designed and planned study protocols, established study measures, and created survey questionnaires. M3 will recruit 1,000-1,200 participants aged ≥18 years, with ∼50% new and ∼50% current MC patients from MC clinics across Florida, USA. Study enrollment started in May 2022 and will continue until the target number of patients is achieved. Survey domains include sociodemographic characteristics, physical and mental health, cannabis use history, reasons for MC use and discontinuation, MC products and use patterns, concurrent use of prescription medications and other substances, and side effects. Data collected in the M3 Study will be available for interested researchers affiliated with the Consortium for Medical Marijuana Clinical Outcomes Research. The M3 Study and Databank will be the largest cohort of current and new MC users in Florida, USA, which will provide data to support MC-related health research necessary to inform policy and clinical practice and ultimately improve patient outcomes.

Validation of an ICD-9-Based Algorithm to Identify Stillbirth Episodes from Medicaid Claims Data.

INTRODUCTION: In administrative data, accurate timing of exposure relative to gestation is critical for determining the effect of potential teratogen exposure on pregnancy outcomes. OBJECTIVE: To develop an algorithm for identifying stillbirth episodes in the ICD-9-CM era using national Medicaid claims data (1999-2014). METHODS: Unique stillbirth episodes were identified from clusters of medical claims using a hierarchy that identified the encounter with the highest potential of including the actual stillbirth delivery and that delineated subsequent pregnancy episodes. Each episode was validated using clinical detail on retrieved medical records as the gold standard. RESULTS: Among 220 retrieved records, 197 were usable for validation of 1417 stillbirth episodes identified by the algorithm. The positive predictive value (PPV) was 64.0% (57.3-70.7%) overall, 80.4% (73.8-87.1%) for inpatient episodes, 28.2% (14.1-42.3%) for outpatient-only episodes, and 20.0% (2.5-37.5%) for outpatient episodes with overlapping hospitalizations. The absolute difference between the dates of the algorithm-specified stillbirth delivery and the medical record-based event was 4.2 ± 24.3 days overall, 1.7 ± 7.7 days for inpatient episodes, 14.3 ± 51.4 days for outpatient-only episodes, and 1.0 ± 2.0 days for outpatient episodes that overlapped with a hospitalization. Excluding all outpatient episodes, as well as pregnancies involving multiple births, the PPV increased to 82.7% (76.8-89.8%). CONCLUSIONS: Our algorithm to identify stillbirths from administrative claims data had a moderately high PPV. Positive predictive value was substantially increased by restricting the setting to inpatient episodes and using only input diagnostic codes for singleton stillbirths.

Risk of fetal or neonatal death or neonatal intensive care unit admission associated with gadolinium magnetic resonance imaging exposure during pregnancy.

BACKGROUND: Concerns have been raised about prenatal exposure to magnetic resonance imaging with gadolinium-based contrast agents because of nonclinical findings of gadolinium retention in fetal tissue and 1 population-based study reporting an association with adverse pregnancy outcomes. OBJECTIVE: This study aimed to evaluate the association between prenatal magnetic resonance imaging exposure with and without gadolinium-based contrast agents and fetal and neonatal death and neonatal intensive care unit admission. STUDY DESIGN: We constructed a retrospective cohort of >11 million Medicaid-covered pregnancies between 1999 and 2014 to evaluate the association between prenatal magnetic resonance imaging exposure with and without gadolinium-based contrast agents and fetal and neonatal death (primary endpoint) and neonatal intensive care unit admissions (secondary endpoint). Medicaid claims data were linked to medical records, Florida birth and fetal death records, and the National Death Index to validate the outcomes and gestational age estimates. Pregnancies with multiples, concurrent cancer, teratogenic drug exposure, magnetic resonance imaging focused on fetal or pelvic evaluation, undetermined gadolinium-based contrast agent use, or those preceded by or contemporaneous with congenital anomaly diagnoses were excluded. We adjusted for potential confounders with standardized mortality ratio weighting using propensity scores. RESULTS: Among 5991 qualifying pregnancies, we found 11 fetal or neonatal deaths in the gadolinium-based contrast agent magnetic resonance imaging group (1.4%) and 73 in the non-gadolinium-based contrast agent magnetic resonance imaging group (1.4%) with an adjusted relative risk of 0.73 (95% confidence interval, 0.34-1.55); the neonatal intensive care unit admission adjusted relative risk was 1.03 (0.76-1.39). Sensitivity analyses investigating the timing of magnetic resonance imaging or repeat magnetic resonance imaging exposure during pregnancy and simulating the impact of exposure misclassification corroborated these results. CONCLUSION: This study addressed the safety concerns related to prenatal exposure to gadolinium-based contrast agents used in magnetic resonance imaging and the risk thereof on fetal and neonatal death or the need for neonatal intensive care unit admission. Although the results on fatal or severe acute effects are reassuring, the impact on subacute outcomes was not evaluated.

Proceedings of the 2022 Cannabis Clinical Outcomes Research Conference.

The Consortium for Medical Marijuana Clinical Outcomes Research, a multi-university collaboration established by the state of Florida in the USA, hosted its second annual Cannabis Clinical Outcomes Research Conference (CCORC) in May 2022. CCORC was held as a hybrid conference, with a scientific program consisting of in-person and virtual sessions. CCORC fostered and disseminated current research on clinical outcomes of medical marijuana while stimulating collaboration and engagement between the scientific community, policymakers, industry representatives, clinicians, and other interested stakeholders. Three themes emerged from conference sessions and speakers: (1) disentangling research findings comparing use and outcomes of medical and nonmedical cannabis, (2) addressing barriers and promoting facilitators for clinical cannabis research, and (3) resolving uncertainties around cannabis dosing. The third annual CCORC is planned for the summer of 2023 in Florida, USA.

Watchful Waiting for Acute Otitis Media.

BACKGROUND AND OBJECTIVES: Updated guidelines continue to support watchful waiting as an option for uncomplicated acute otitis media (AOM) and provide explicit diagnostic criteria. To determine treatment prevalence and associated determinants of watchful waiting for AOM in commercially insured pediatric patients. METHODS: This was a retrospective cohort study using IBM Marketscan Commercial Claims Databases (2005 to 2019) of patients 1 to 12 years old with AOM, without otitis-related complications within 6 months prior, with no tympanostomy tubes, and no other infections around index diagnosis of AOM. We examined monthly antibiotic treatment prevalence (defined as pharmacy dispensing within 3 days of AOM diagnosis) and used multivariable logistic regression models to examine determinants of watchful waiting. RESULTS: Among 2 176 617 AOM episodes, 77.8% were treated within 3 days. Whereas some clinical characteristics were moderate determinants for watchful waiting, clinician antibiotic prescribing volume and specialty were strong determinants. Low-volume antibiotic prescribers (≥80% of AOM episodes managed with watchful waiting) had 11.61 (95% confidence interval 10.66-12.64) higher odds of using watchful waiting for the index AOM episode than high-volume antibiotic prescribers (≥80% treated). Otolaryngologists were more likely to adopt watchful waiting (odds ratio 5.45, 95% CI 5.21-5.70) than pediatricians, whereas other specialties deferred more commonly to antibiotics. CONCLUSIONS: Adoption of watchful waiting for management of uncomplicated, nonrecurrent AOM was limited and stagnant across the study period and driven by clinician rather than patient factors. Future work should assess motivators for prescribing and evaluate patient outcomes among clinicians who generally prefer versus reject watchful waiting approaches to guide clinical decision-making.

Prenatal exposure to teratogenic medications in the era of Risk Evaluation and Mitigation Strategies.

BACKGROUND: Prevention of prenatal exposures to teratogenic drugs is a significant clinical and public health concern. With the enactment of the US Food and Drug Administration Amendments Act in 2007, the US Food and Drug Administration has begun to require manufacturers to implement Risk Evaluation and Mitigation Strategies to prevent prenatal exposures. Among 12 risk evaluation and mitigation strategy drugs, several had predecessor risk mitigation plans (eg, isotretinoin) and some were newly required (eg, mycophenolate). Only a small proportion of teratogenic drugs are currently subject to Risk Evaluation and Mitigation Strategies, and the extent of prenatal exposure to the universe of teratogenic drugs compared with drugs subject to Risk Evaluation and Mitigation Strategies is unknown. Moreover, the effectiveness of such advanced risk mitigation programs in preventing prenatal exposure is not clear. OBJECTIVE: This study aimed to characterize the epidemiology of prenatal exposures to definite and potential teratogens during the risk evaluation and mitigation strategy era. STUDY DESIGN: We constructed a time-series of pregnancies identified from a national private insurance claims database (IBM MarketScan) to estimate prenatal exposures to teratogenic drugs (2006-2017). Pregnancy outcomes, gestational age, and the onset of pregnancy were determined with previously validated algorithms. The Teratology Information Service and Clinical Pharmacology databases were used to identify drugs with definite (n=141) or potential (n=65) teratogenic effects, and drugs with debatable risks such as benzodiazepines, statins, tetracyclines, sex hormones, infertility treatments, and gonadotropin-releasing hormone analogs were excluded. We defined prenatal exposure as ≥1 prescription fill or medical encounter involving administration of drugs with a definite teratogenic risk (including 12 for which there is a "current or discontinued" risk evaluation and mitigation strategy) or a potential teratogenic risk. We evaluated secular trends and modeled the effects of age, preconception exposure, and state healthcare quality rankings on prenatal exposure, adjusting for demographic factors and clinical conditions. RESULTS: The cohort included 3,445,612 pregnancies (2,532,444 live deliveries). Prenatal exposures to definite teratogens decreased slightly during the study years from 1.86 to 1.24 per 100 pregnancies between 2006 and 2017, whereas exposure increased for potential teratogens from 3.40% to 5.33%. Prenatal exposure prevalences were higher during the first trimester and for pregnancies that ended in nonlive outcomes. Drugs subject to Risk Evaluation and Mitigation Strategies had low background utilization and contributed to a small proportion of prenatal exposures (15.1 per 100,000 pregnancies). We also observed fewer prenatal exposures to risk evaluation and mitigation strategy drugs among women of childbearing age who used these treatments (0.14% vs 0.36% for any definite teratogen). Age extremes and low state-level healthcare quality rankings were independent predictors of prenatal exposure. CONCLUSION: Fetuses in more than 1 in 16 pregnancies continued to be exposed to teratogenic drugs during the past decade. Drugs with Risk Evaluation and Mitigation Strategies imposed a small burden of prenatal exposure because of the low background utilization rates and lower pregnancy prevalence among women of childbearing age who used these drugs. Although the declining exposure rates to teratogenic drugs with definite risk are encouraging, the rising prenatal exposure to drugs with potential risk calls for more assessments. Future research is needed to elucidate the health outcomes of fetuses exposed to potential risk drugs, understand the effectiveness of risk evaluation and mitigation strategy programs, and prioritize teratogenic drugs for advanced risk mitigation.