Prenatal opioid exposure by likelihood of exposure and risk to prenatal development: Medicaid-covered births in Wisconsin, 2010-2019.

Prenatal opioid exposure is an established public health problem, in particular among Medicaid-covered births. Yet, existing prevalence rates are plausibly underestimated. We leverage extensive linked longitudinal administrative data for all Medicaid-covered live births in Wisconsin from 2010 to 2019 to estimate a range of prevalence rates using an innovative strategy that jointly accounts for both likelihood of exposure and potential risk to prenatal development. We find that 20.8% of infants may have been prenatally exposed to opioids, with 1.7% diagnosed with neonatal abstinence syndrome and an additional 1.2% having a high combined likelihood of exposure and potential risk to prenatal development, 2.6% a moderate combined likelihood and risk, and 15.3% a low or uncertain combined likelihood and risk. We assess improvements in prevalence estimates based on our nuanced classification relative to those of prior studies. Our strategy could be broadly used to quantify the scope of the opioid crisis for pregnant populations, target interventions, and promote child health and development.

Neonatal Abstinence Syndrome and Corresponding Pharmacotherapy Approaches from 2 University-affiliated Neonatal Intensive Care Units in Puerto Rico (2018-2020).

OBJECTIVE: Neonatal abstinence syndrome (NAS) is a set of drug withdrawal symptoms suffered by neonates exposed to drugs in utero. Several studies have widely described NAS incidence and treatment approach; however, little is known regarding the incidence and manifestations of this disease in Puerto Rico (PR). The principal aim of this study was to describe NAS incidence in the neonatal units of hospitals affiliated with the University of PR in terms of occurrence, clinical manifestations, and treatment approaches. METHODS: Our study evaluated the medical records of NAS babies diagnosed from 2018 through 2020 at 2 hospitals affiliated with the University of PR Medical Sciences Campus. Descriptive and inferential statistics were employed to analyze trends. RESULTS: We identified 12 neonates diagnosed with NAS, 5 with low birthweights (<2500 g); for a NAS incidence of 2 cases per 1000 admitted for the 3 years of recollected data. The urine toxicology results revealed that 9 had experienced intrauterine polydrug exposure. Phenobarbital loading dose were determined on the day of diagnosis (indicated by Finnegan score). The first manifestation of NAS symptoms varied: 8 neonates showed symptoms within 48 hours after birth, whereas 4 had withdrawal symptoms within 72-120 hours of their births. Differences between dosing practices and guidelines were observed, ranging from a 0.69% to a 25% difference during treatment initiation. CONCLUSION: Further research on the incidence of NAS in PR (national level) is needed for a deeper understanding that we hope will lead to the development of enhanced treatment protocols in PR.

COVID-19 Pandemic-Related Changes in Rates of Neonatal Abstinence Syndrome.

This cross-sectional study examines COVID-19 pandemic­related changes in rates of neonatal abstinence syndrome (NAS) and whether infants in urban or rural areas and those with low socioeconomic status were disproportionately affected.

Cost of Care for Newborns With Neonatal Abstinence Syndrome in a State Medicaid Program.

Importance: Neonatal abstinence syndrome (NAS) is a medical condition among neonates experiencing substance withdrawal due to the mother's substance use during pregnancy. While previous studies suggest that the overall incidence and annual costs of NAS are increasing, to date, the long-term costs have yet to be demonstrated in Medicaid populations. Objective: To examine the demographic differences and long-term costs of care for neonates diagnosed with vs not diagnosed with NAS. Design, Setting, and Participants: This cohort study used claims data from the Alabama Medicaid Agency for neonates born to Medicaid-eligible mothers between January 1, 2010, and December 31, 2020. Data were analyzed in June 2022. Exposure: A diagnosis of NAS within 30 days of birth. Main Outcomes and Measures: Rate of NAS by demographic and birth characteristics, long-term costs attributable to NAS status and demographic and birth characteristics, and distribution of this expenditure over the enrollment period. Results: A total of 346 259 neonates with Medicaid eligibility were born during the study period (mean [SD] gestational age, 38.4 [2.2] weeks; 50.5%, male), 4027 (1.2%) of whom had an NAS diagnosis within 30 days of birth. A larger percentage of neonates with an NAS diagnosis were male (52.7%) than in the group without NAS (50.5%). Neonates with NAS also weighed less at birth (mean difference, -212.0 g; 95% CI, -231.1 to -192.8 g) and had older mothers (mean difference, 3.4 years; 95% CI, 2.6-4.2 years). An NAS diagnosis had an estimated additional cost of $17 921 (95% CI, $14 830-$21 012) over the enrollment period, and this cost was not evenly distributed over that period. Conclusions and Relevance: In this cohort study of neonates born into the Alabama Medicaid population, those with an NAS diagnosis had a different demographic profile and a higher cost to state Medicaid agencies than those without NAS. These findings warrant further effort to reduce the occurrence of NAS.

Prenatal Opioid Exposure and Immune-Related Conditions in Children.

Importance: Prenatal opioid exposure (POE) may alter with fetal development of the immune system, which may influence long-term health and susceptibility to immune-related conditions. Objective: To compare the risk of hospitalization and emergency department presentation for immune-related conditions in children with and without POE. Design, Setting, and Participants: This retrospective, population-based cohort study used linked administrative health records of all children born in Western Australia between January 1, 2003, and December 31, 2018 (N = 401 462). Exposure: Prenatal exposure to prescription opioids (overall and by trimester), neonatal abstinence syndrome diagnosis, and opioid indication (pain or opioid use disorder [OUD]). Main Outcomes and Measures: The main outcome was hospital admissions and emergency department presentations during which a child was diagnosed with an immune-related condition, including infections, conditions associated with an overactive immune system (eg, asthma, eczema, and allergy and anaphylaxis), and autoimmune diseases diagnosed before age 5 years or June 30, 2020. Data were analyzed between August 30, 2022, and February 27, 2023. Results: Neonates with POE (1656 [0.4%]; mean [SD] gestational age, 37.7 [2.1] weeks; 836 females [50.5%]; 820 males [49.5%]) were more likely to be born preterm, have low birth weight for gestational age, and be coexposed to cigarette smoke compared with nonexposed neonates. Perinatal opioid exposure was associated with an increased risk of perinatal infection (adjusted odds ratio [AOR], 1.62; 95% CI, 1.38-1.90) and eczema and dermatitis (AOR, 11.91; 95% CI, 9.84-14.41) compared with nonexposure. Neonatal abstinence syndrome was also associated with both conditions (AOR, 2.91 [95% CI, 2.36-3.57] and 31.11 [95% CI, 24.64-39.28], respectively). Prenatal opioid exposure was also associated with an increased risk of childhood asthma (adjusted hazard ratio [AHR], 1.44; 95% CI, 1.16-1.79), but not allergies and anaphylaxis. It was also associated with an increased risk of childhood eczema and dermatitis, but only in children with POE from opioids used to treat OUD (AHR, 1.47; 95% CI, 1.08-1.99) rather than pain. In contrast, POE from opioids used for pain was associated with an increased risk of infection (AHR, 1.44; 95% CI, 1.32-1.58), but POE to opioids used to treat OUD was not. Autoimmune conditions were rare and were not observed to be associated with POE. Conclusions and Relevance: In this cohort study, POE was associated with an increased risk of infection, eczema and dermatitis, and asthma, but not allergies and anaphylaxis or autoimmune conditions. These findings highlight the importance of further study of opioid-induced immune changes during pregnancy, the potential impact on long-term health in exposed children, and the mechanisms of opioid-induced immune dysregulation.

Considerations and Determinants of Discharge Decisions among Prenatal Substance Exposed Infants.

Limited research has examined a comprehensive set of predictors when evaluating discharge placement decisions for infants exposed to substances prenatally. Using a previously validated medical record data extraction tool, the current study examined prenatal substance exposure, infant intervention (i.e., pharmacologic, or non-pharmacologic), and demographic factors (e.g., race and ethnicity and rurality) as predictors of associations with discharge placement in a sample from a resource-poor state (N = 136; 69.9% Non-Hispanic White). Latent class analysis (LCA) was used to examine whether different classes emerged and how classes were differentially related to discharge placement decisions. Logistic regressions were used to determine whether each predictor was uniquely associated with placement decisions. Results of the LCA yielded a two-class solution comprised of (1) a Low Withdrawal Risk class, characterized by prenatal exposure to substances with low risk for neonatal abstinence syndrome (NAS) and non-pharmacologic intervention, and (2) a High Withdrawal Risk class, characterized by a high risk of NAS and pharmacologic intervention. Classes were not related to discharge placement decisions. Logistic regressions demonstrated that meth/amphetamine use during pregnancy was associated with greater odds of out of home placement above other substance types. Future research should replicate and continue examining the clinical utility of these classes.

Inclusion of Sex and Gender Differences in U.S. State Action Plans for Opioid Use and Opioid Use Disorder.

Background: States have developed action plans to address the "opioid crisis" over the past several years. While sex- and gender-based differences have been identified in complications of opioid use, risks of addiction to opioids, barriers to treatment of opioid use disorder, and associated stigma, it is unknown if or to what extent opioid plans consider or account for these differences. The objectives of this study were to analyze U.S. state opioid action plans and their inclusion of sex- and gender-specific concerns. Methods: A content analysis of 49 state plans was conducted in June 2020, assessing their inclusion of 14 variables covering provider education, pregnancy-related, and sex- or gender-based differences in opioid addiction and treatment. Results: Neonatal opioid withdrawal syndrome was the most common variable, noted in 57% of plans. Only 14% included pregnancy-related stigma, and 4% identified gender-specific stigma. Contraceptives and family-planning were included in 12% and 10% of plans, respectively. Two states included more than half of the variables and five plans made no mention of sex or gender differences. Conclusions: Few state plans contained sex- or gender-specific information, and those that did focused almost exclusively on childbearing, excluding other unique considerations of opioid-using-women of all ages. The results of this study could improve the care of women using opioids by informing the strategies of state agencies and impacting legislative efforts for prevention initiatives, substance use disorder treatment, and law enforcement programs.

Trends in Neonatal Opioid Withdrawal Syndrome and Opioid Exposure Diagnoses Among Infants With Private Health Insurance, 2016-2021: Introduction of the P04.14 ICD-10-CM Code.

OBJECTIVE: The opioid epidemic has led to a surge in diagnoses of neonatal opioid withdrawal syndrome (NOWS). Many states track the incidence of NOWS by using the P96.1 International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code for "neonatal withdrawal symptoms from maternal use of drugs of addiction." In October 2018, an ICD-10-CM code for neonatal opioid exposure (P04.14) was introduced. This code can be used when an infant is exposed to opioids in utero but does not have clinically significant withdrawal symptoms. We analyzed the effect of the P04.14 code on the incidence rate of NOWS (P96.1) and "other" neonatal drug exposure diagnoses (P04.49). METHODS: We used private health insurance data collected for infants in the United States from the first quarter of 2016 through the third quarter of 2021 to describe incidence rates for each code over time and examine absolute and percentage changes before and after the introduction of code P04.14. RESULTS: The exclusive use of code P96.1 declined from an incidence rate per 1000 births of 1.08 in 2016-2018 to 0.70 in 2019-2021, a -35.7% (95% CI, -47.6% to -23.8%) reduction. Use of code P04.49 only declined from an incidence rate of 2.34 in 2016-2018 to 1.64 in 2019-2021, a -30.0% (95% CI, -36.4% to -23.7%) reduction. Use of multiple codes during the course of treatment increased from an average incidence per 1000 births of 0.56 in 2016-2018 to 0.79 in 2019-2021, a 45.5% (95% CI, 24.8%-66.1%) increase. CONCLUSION: The introduction of ICD-10-CM code P04.14 altered the use of other neonatal opioid exposure codes. The use of multiple codes increased, indicating that some ambiguity may exist about which ICD-10-CM code is most appropriate for a given set of symptoms.

Impaired vision in children prenatally exposed to methadone: an observational cohort study.

BACKGROUND/OBJECTIVES: To examine prevalence of failed visual assessment at 8-10 years in children born to methadone-maintained opioid dependent (MMOD) mothers and relate this to known in utero substance exposure. SUBJECTS/METHODS: Follow up of observational cohort study of methadone-exposed and comparison children matched for birthweight, gestation and postcode of residence at birth. Participants were 144 children (98 exposed, 46 comparison). Prenatal drug exposure was previously established via comprehensive maternal and neonatal toxicology. Children were invited to attend for visual assessment and casenotes were reviewed. Presence of acuity poorer than 0.2 logMAR, strabismus, nystagmus and/or impaired stereovision constituted a 'fail'. Fail rates were compared between methadone-exposed and comparison children after adjusting for known confounding variables. RESULTS: 33 children attended in person: data were also derived from casenote review for all children. After controlling for maternal reported tobacco use, methadone-exposed children were more likely to have a visual 'fail' outcome, adjusted odds ratio 2.6, 95% CI 1.1-6.2; adjusted relative risk 1.8 (95% CI 1.1-3.4). Visual 'fail' outcome rates did not differ between methadone-exposed children who had (n = 47) or had not (n = 51) received pharmacological treatment for neonatal abstinence/opioid withdrawal syndrome (NAS/NOWS); fail rate 62% vs 53% (95% CI of difference-11-27%). CONCLUSIONS: Children born to MMOD mothers are almost twice as likely as unexposed peers to have significant visual abnormalities at primary school age. Prenatal methadone exposure should be considered in the differential diagnosis of nystagmus. Findings support visual assessment prior to school entry for children with any history of prenatal opioid exposure. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03603301), https://clinicaltrials.gov/ct2/show/NCT03603301 .

Health Services Use Among Children With Prenatal Substance Exposure or Neonatal Abstinence Syndrome.

OBJECTIVE: Infants with prenatal substance exposure or neonatal abstinence syndrome (NAS) use health services more often than other children; however, little is known about their use of mental health services and psychotropic medication. METHODS: The sample (N=1,004,085) consisted of infants born in 2016 in 38 states who were followed through the fifth year of life and enrolled each year in Medicaid or the Children's Health Insurance Program. Infants with prenatal substance exposure or NAS were identified with ICD-10 diagnosis codes; procedure and revenue codes documented their service use. RESULTS: Rates of any mental health visit and of psychotropic medication use were higher among infants with prenatal substance exposure or NAS compared with infants without either condition; these patterns persisted during most years of the 5-year study. CONCLUSIONS: Infants' elevated mental health services use through their first 5 years of life highlights the importance of early screening and subsequent engagement in school-based mental health interventions.

Regional tissue oxygenation in asymptomatic neonates at high risk for neonatal abstinence syndrome and impact of non-pharmacologic interventions: A case report.

BACKGROUND: Improving neonatal abstinence syndrome (NAS) management is an important concern, and objective measures of its physiologic impact remain elusive. We sought to determine whether near-infrared spectroscopy (NIRS)-derived tissue oxygenation (rSO2) and fractional tissue oxygen extraction (FTOE) demonstrated physiologically plausible changes correlating with standard NAS scoring. METHODS: Thirty subjects (mean 39 weeks' GA and 3 127 g BW) underwent cerebral and peripheral muscle NIRS monitoring on Days of Life (DOL) Three, Five, and Seven. We examined correlations between NAS scores and FTOE and assessed the impact of non-pharmacologic swaddling and cuddling. RESULTS: No statistically significant correlations between NAS scores and FTOE were observed; however, plausible trends were demonstrated between NAS scores and cerebral measurements. Buprenorphine-exposed babies (57%) showed significantly lower FTOE when swaddled (DOL7). CONCLUSIONS: Tissue oxygenation monitoring demonstrates potential to provide objective, clinically relevant physiologic information on infants at risk for NAS. Further study is required to determine whether NIRS-derived measures could assist in individualizing NAS care.

Rise in Neonatal Abstinence Syndrome Rate Is Associated with Increase in Buprenorphine Prescription Numbers.

OBJECTIVES: Southern Appalachia is a region of the United States that is disproportionately affected by the opioid epidemic and by increasing rates of neonatal abstinence syndrome (NAS). NAS rates increased approximately 400% between 1999 and 2012. Buprenorphine prescriptions written to treat opioid use disorder also increased dramatically. The present study was undertaken to ascertain any relationship between the number of buprenorphine prescriptions compared with NAS rates in southern Appalachia. METHODS: A total of 250 southern Appalachian counties across seven states, including all of West Virginia and portions of Virginia, Kentucky, Maryland, North Carolina, Ohio, and Tennessee were identified. A retrospective cohort analysis of these counties was conducted for the years 2005-2018. All of the data were obtained from publicly accessible sources or direct communication with government offices. Measures from each county in southern Appalachia included annual NAS rates, buprenorphine prescription rates, drug-induced death rates, and opioid prescribing rates. Associations among these variables were examined using a generalized linear regression. RESULTS: Significant linear associations exist between the rising rate of NAS diagnoses and the rising rate of buprenorphine prescriptions (r = 0.977, R2 = 95.53%, P < 0.001) and between the rising rate of buprenorphine prescriptions and the increase in drug-induced deaths (r = 0.712, R2 = 50.82%, P = 0.031). CONCLUSIONS: This is the first report that documents an association between rising NAS rates and increasing buprenorphine prescribing. Between the years 2010 and 2018, the NAS rate in southern Appalachia rose by 335%, and the number of buprenorphine prescriptions rose by 413%. Discussions regarding the current policies for buprenorphine management during pregnancy are warranted. We suggest a reevaluation of buprenorphine prescribing recommendations during pregnancy and further research on establishing the lowest effective buprenorphine dose for each pregnant patient.

Decreased myelin-related gene expression in the nucleus accumbens during spontaneous neonatal opioid withdrawal in the absence of long-term behavioral effects in adult outbred CFW mice.

Prenatal opioid exposure is a major health concern in the United States, with the incidence of neonatal opioid withdrawal syndrome (NOWS) escalating in recent years. NOWS occurs upon cessation of in utero opioid exposure and is characterized by increased irritability, disrupted sleep patterns, high-pitched crying, and dysregulated feeding. The main pharmacological strategy for alleviating symptoms is treatment with replacement opioids. The neural mechanisms mediating NOWS and the long-term neurobehavioral effects are poorly understood. We used a third trimester-approximate model in which neonatal outbred pups (Carworth Farms White; CFW) were administered once-daily morphine (15 mg/kg, s.c.) from postnatal day (P) day 1 through P14 and were then assessed for behavioral and transcriptomic adaptations within the nucleus accumbens (NAc) on P15. We also investigated the long-term effects of perinatal morphine exposure on adult learning and reward sensitivity. We observed significant weight deficits, spontaneous thermal hyperalgesia, and altered ultrasonic vocalization (USV) profiles following repeated morphine and during spontaneous withdrawal. Transcriptome analysis of NAc from opioid-withdrawn P15 neonates via bulk mRNA sequencing identified an enrichment profile consistent with downregulation of myelin-associated transcripts. Despite the neonatal behavioral and molecular effects, there were no significant long-term effects of perinatal morphine exposure on adult spatial memory function in the Barnes Maze, emotional learning in fear conditioning, or in baseline or methamphetamine-potentiated reward sensitivity as measured via intracranial self-stimulation. Thus, the once daily third trimester-approximate exposure regimen, while inducing NOWS model traits and significant transcriptomic effects in neonates, had no significant long-term effects on adult behaviors.

Duration and Timing of In Utero Opioid Exposure and Incidence of Neonatal Withdrawal Syndrome.

OBJECTIVE: To evaluate the association between prenatal prescription opioid analgesic exposure (duration, timing) and neonatal opioid withdrawal syndrome (NOWS). METHODS: We conducted a retrospective cohort study of Wisconsin Medicaid-covered singleton live births from 2011 to 2019. The primary outcome was a NOWS diagnosis in the first 30 days of life. Opioid exposure was identified with any claim for prescription opioid analgesic fills during pregnancy. We measured exposure duration cumulatively in days (1-6, 7-29, 30-89, and 90 or more) and identified timing as early (first two trimesters only) or late (third trimester, regardless of earlier pregnancy use). We used logistic regression modeling to assess NOWS incidence by exposure duration and timing, with and without propensity score matching. RESULTS: Overall, 31,456 (14.3%) of 220,570 neonates were exposed to prescription opioid analgesics prenatally. Among exposed neonates, 19,880 (63.2%) had 1-6 days of exposure, 7,694 (24.5%) had 7-29 days, 2,188 (7.0%) had 30-89 days, and 1,694 (5.4%) had 90 or more days of exposure; 15,032 (47.8%) had late exposure. Absolute NOWS incidence among neonates with 1-6 days of exposure was 7.29 per 1,000 neonates (95% CI 6.11-8.48), and incidence increased with longer exposure: 7-29 days (19.63, 95% CI 16.53-22.73); 30-89 days (58.96, 95% CI 49.08-68.84); and 90 or more days (177.10, 95% CI 158.90-195.29). Absolute NOWS incidence for early and late exposures were 11.26 per 1,000 neonates (95% CI 9.65-12.88) and 35.92 per 1,000 neonates (95% CI 32.95-38.90), respectively. When adjusting for confounders including timing of exposure, neonates exposed for 1-6 days had no increased odds of NOWS compared with unexposed neonates, whereas those exposed for 30 or more days had increased odds of NOWS (30-89 days: adjusted odds ratio [aOR] 2.15, 95% CI 1.22-3.79; 90 or more days: 2.80, 95% CI 1.36-5.76). Late exposure was associated with elevated odds of NOWS (aOR 1.57, 95% CI 1.25-1.96) when compared with unexposed after adjustment for exposure duration. CONCLUSION: More than 30 days of prenatal prescription opioid exposure was associated with NOWS regardless of exposure timing. Third-trimester opioid exposure, irrespective of exposure duration, was associated with NOWS.

Impact of an Asynchronous Training for the Early Intervention and Childcare Workforce Addressing the Developmental Impact of the Opioid Crisis on Young Children.

OBJECTIVES: The US opioid epidemic contributes to a growing population of children experiencing neonatal abstinence syndrome (NAS) and adverse childhood experiences (ACEs). A review of the developmental impacts of the opioid crisis highlights that both prenatal exposure to teratogens and ACEs can result in developmental delay and disabilities. Training for the early intervention/early childhood (EI) systems is needed to enable them to meet the needs of this growing population. METHODS: To address this, an IRB-approved online training on best practices for NAS, developmental monitoring and referral, and trauma-informed care was created for Ohio EI providers who provided informed consent to participate. The feasibility of utilizing an online training was assessed. Knowledge on opioid addiction, NAS, ACEs, and early intervention provider characteristics were collected for 2973 participants. RESULTS: Within 6 months, the training reached providers in all Ohio counties and seventeen other states. 57% of providers reported caring for one or more children with a caregiver who has confirmed opioid use. 31% reported these children had experienced four or more ACEs. Providers' ACEs awareness was moderately associated with their experiences with prenatally-exposed youth. There was a significant increase in knowledge following training. Differences in post-training knowledge differed only by county-level opioid death rates, where those providers with low-medium opioid death rates reported more awareness of children with prenatal opioid exposure compared to participants who lived in a county with medium and medium-high opioid death rates. CONCLUSIONS: Online-training is feasible for closing gaps in the early intervention system.

Maternal Opioid Use Disorder and the Risk of Postneonatal Infant Mortality.

Importance: The risk of serious long-term outcomes for infants born to individuals with opioid use disorder (OUD) is not fully characterized, nor is it well understood whether risks are modified by infant diagnosis of neonatal opioid withdrawal syndrome (NOWS). Objective: To characterize the risk of postneonatal infant mortality among infants with a NOWS diagnosis or born to individuals with OUD. Design, Setting, and Participants: The study team conducted a retrospective cohort study of 390 075 infants born from 2007 through 2018 to mothers who were enrolled in Tennessee Medicaid from 183 days prior to delivery through 28 days post partum (baseline). Maternal and infant baseline characteristics were measured using administrative claims and birth certificates, and infants were followed up from day 29 post partum through day 365 or death. Deaths were identified using linked death certificates through 2019. These data were analyzed from February 10, 2022, through March 3, 2023. Exposure: Infant exposures included birth to an individual with OUD or postnatal diagnosis of NOWS. The study team defined a pregnant individual's OUD status (maternal OUD) as having OUD diagnosis or a maintenance medication prescription fill during baseline; this study defined NOWS as having NOWS diagnosis up to day 28. Groups were categorized by exposures as maternal OUD with NOWS (OUD positive/NOWS positive), maternal OUD without NOWS (OUD positive/NOWS negative), no documented maternal OUD with NOWS (OUD negative/NOWS positive), and no documented maternal OUD or NOWS (OUD negative/NOWS negative, unexposed). Main Outcome and Measures: The outcome was postneonatal infant death, confirmed by death certificates. Cox proportional hazards models were used, adjusting for baseline maternal and infant characteristics, to estimate adjusted hazard ratios (aHRs) and 95% CIs for the association between maternal OUD or NOWS diagnosis with postneonatal death. Results: Pregnant individuals in the cohort had a mean (SD) age of 24.5 (5.2) years; 51% of infants were male. The study team observed 1317 postneonatal infant deaths and incidence rates of 3.47 (OUD negative/NOWS negative, 375 718), 8.41 (OUD positive/NOWS positive, 4922); 8.95 (OUD positive/NOWS negative, 7196), and 9.25 (OUD negative/NOWS positive, 2239) per 1000 person-years. After adjustment, the risk of postneonatal death was elevated for all groups, relative to the unexposed: OUD positive/NOWS positive (aHR, 1.54; 95% CI, 1.07-2.21), OUD positive/NOWS negative (aHR, 1.62; 95% CI, 1.21-2.17), and OUD negative/NOWS positive (aHR, 1.64; 95% CI, 1.02-2.65). Conclusions and Relevance: Infants born to individuals with OUD or with a NOWS diagnosis had an increased risk of postneonatal infant mortality. Future work is necessary to create and evaluate supportive interventions for individuals with OUD during and after pregnancy to reduce adverse outcomes.

Demographics, Birth Parameters, and Social Determinants of Health Among Opioid-Exposed Mother-Infant Dyads Affected by Neonatal Abstinence Syndrome in Pennsylvania, 2018-2019.

OBJECTIVES: To characterize demographics, birth parameters, and social determinants of health among mother-infant dyads affected by neonatal abstinence syndrome (NAS) in Pennsylvania. METHODS: We linked 2018-2019 NAS surveillance data to birth record data using probabilistic methods and then geospatially linked to local social determinants of health data based on residential address. We generated descriptive statistics and used multivariable mixed-effects logistic regression to model the association between maternal characteristics, birth parameters, social determinants of health, and NAS. RESULTS: In adjusted models maternal age > 24, non-Hispanic white race/ethnicity, low educational attainment, Medicaid as payor at delivery, inadequate or no prenatal care, smoking during pregnancy, and low median household income were associated with NAS. We found no significant associations between NAS and county-level measures of clinician supply, number of substance use treatment facilities, or urban/rural designation. CONCLUSIONS FOR PRACTICE: This study characterizes mother-infant dyads affected by NAS using linked non-administrative, population data for Pennsylvania. Results demonstrate a social gradient in NAS and inequity in prenatal care receipt among mothers of infants with NAS. Findings may inform implementation of state-based public health interventions.

Prenatal Substance Exposure and Neonatal Abstinence Syndrome: State Estimates from the 2016-2020 Transformed Medicaid Statistical Information System.

INTRODUCTION: Estimating Neonatal Abstinence Syndrome (NAS) and prenatal substance exposure rates in Medicaid can help target program efforts to improve access to services. METHODS: The data for this study was extracted from the 2016-2020 Transformed Medicaid Statistical Information System (T-MSIS) Analytic Files (TAF) Research Identifiable Files (RIF) and included infants born between January 1, 2016 and December 31, 2020 with a either a NAS diagnosis or prenatal substance exposure. RESULTS: Between 2016 and 2020, the estimated national rate of NAS experienced a 18% decline, while the estimated national rate of prenatal substance exposure experienced a 3.6% increase. At the state level in 2020, the NAS rate ranged from 3.2 per 1000 births (Hawaii) to 68.0 per 1000 births (West Virginia). Between 2016 and 2020, 28 states experienced a decline in NAS births and 20 states had an increase in NAS rates. In 2020, the lowest prenatal substance exposure rate was observed in New Jersey (9.9 per 1000 births) and the highest in West Virginia (88.1 per 1000 births). Between 2016 and 2020, 38 states experienced an increase in the rate of prenatal substance exposure and 10 states experienced a decline. DISCUSSION: Estimated rate of NAS has declined nationally, but rate of prenatal substance exposure has increased, with considerable state-level variation. The reported increase in prenatal substance exposure in the majority of US states (38) suggest that substances other than opioids are influencing this trend. Medicaid-led initiatives can be used to identify women with substance use and connect them to services.

What is already known about the topic? Neonatal Abstinence Syndrome (NAS) and prenatal substance exposure are significant risk factors for poor neurodevelopmental and mental health outcomes in early childhood. NAS birth rates have been increasing in the US since 2000 and the majority of NAS births are covered by Medicaid.What this article adds? This article estimates national and state-level prenatal substance exposure and NAS rates among Medicaid-covered infants born between 2016-2020 using data from the Transformed Medicaid Statistical Information System. This is the first study using post-2017 data to estimate national NAS rates. The findings can inform future federal and state policy efforts to improve access to screening, diagnosis and treatment among pregnant women with substance use disorder and infants with NAS.