Assessing the Impact of Prenatal Medication for Opioid Use Disorder on Discharge Home With Parents Among Infants With Neonatal Opioid Withdrawal Syndrome.

059 Use of medication for opioid use disorder and other prescription opioids among mothers of infants with neonatal opioid withdrawal syndrome: North Carolina Medicaid, 2016–2018

Differences in Mortality Among Infants With Neonatal Opioid Withdrawal Syndrome

Maternal opioid use disorder and infant mortality in Wisconsin, United States, 2010–2018

To evaluate the severity of neonatal opioid withdrawal syndrome (NOWS) in infants prenatally exposed to medications for opioid use disorder (MOUD) and serotonin reuptake inhibitors (SRI). A prospective cohort included 148 maternal-infant pairs categorized into MOUD (n = 127) and MOUD + SRI (n = 27) groups. NOWS severity was operationalized as the infant's need for pharmacologic treatment with opioids, duration of hospitalization, and duration of treatment. The association between prenatal SRI exposure and the need for pharmacologic treatment (logistic regression), time-to-discharge, and time-to-treatment discontinuation (Cox proportional hazards modeling) was examined after adjusting for the type of maternal MOUD, use of hydroxyzine, other opioids, benzodiazepines/sedatives, alcohol, tobacco, marijuana, gestational age, and breastfeeding. Infants in the MOUD + SRI group were more likely to receive pharmacologic treatment for NOWS (OR = 3.58; 95% CI: 1.31; 9.76) and had a longer hospitalization (median: 11 vs. 6 days; HR = 0.54; 95% CI: 0.33; 0.89) compared to the MOUD group. With respect to time-to-treatment discontinuation, no association was observed in infants who received treatment (HR = 0.59; 95% CI: 0.26, 1.32); however, significant differences were observed in the entire sample (HR = 0.55; 95% CI: 0.34, 0.89). Use of SRIs among pregnant women on MOUD might be associated with more severe NOWS. A potential drug-drug interaction between maternal SRIs and opioid medications that inhibit the reuptake of serotonin has been hypothesized but not carefully evaluated in clinical studies. Results of this prospective cohort indicate that the use of SRIs among pregnant women on MOUD is associated with more severe neonatal opioid withdrawal syndrome. This is the first prospective study which carefully examined effect modification between the type of maternal MOUD and SRI use on neonatal outcomes. This report lays the foundation for treatment optimization in pregnant women with co-occurring mental health and substance use disorders.

INTRODUCTION: Our multidisciplinary “Partnering for the Future” (PFF) clinic cares for birthing people with a mood or substance use disorder, including patients receiving medications for opioid use disorder (MOUD). The purpose of this study was to summarize the neonatal outcomes among infants born to patients receiving MOUD. METHODS: We conducted a retrospective analysis of all patients receiving care in our PFF clinic from January 2019 to August 2021. We excluded patients who were not maintained on MOUD and those only seen for consultation. Neonatal characteristics were abstracted from the medical record. Descriptive statistics were computed in SPSS v27. This study was deemed exempt by the institutional review board RESULTS: A total of 92 maternal-infant pairs were identified, of whom 49 patients were taking MOUD, resulting in 51 (54.3%) opioid-exposed infants (two twin pregnancies). Methadone exposure occurred in 21 (43%) pregnancies and buprenorphine exposure in 28 (57%). Neonatal intensive care unit (NICU) admission occurred in 45% (23/51) of infants. Neonatal opioid withdrawal syndrome (NOWS) was diagnosed in 26 (51.0%) infants, with 69% (18/26) infants developing severe NOWS meeting criteria for treatment. Severe NOWS occurred in 57% (12/21) of methadone-exposed pregnancies and 21% (6/28) of buprenorphine-exposed pregnancies. Among the 18 neonates diagnosed with severe NOWS, the average time to initial NOWS diagnosis was 22.35 (±0.86) hours compared to 40.4 (±0.70) hours for neonates diagnosed with non-severe NOWS. CONCLUSION: Severe NOWS was more prevalent among infants exposed to methadone and diagnosed sooner than non-severe NOWS cases. Strategies are needed to reduce NICU admissions and identify infants at highest risk for severe NOWS.

Objectives. To estimate use of medication for opioid use disorder (MOUD) and prescription opioids in pregnancy among mothers of infants with neonatal opioid withdrawal syndrome (NOWS). Methods. We used linked 2016-2018 North Carolina birth certificate and newborn and maternal Medicaid claims data to identify infants with an NOWS diagnosis and maternal claims for MOUD and prescription opioids in pregnancy (n = 3395). Results. Among mothers of infants with NOWS, 38.6% had a claim for MOUD only, 14.3% had a claim for prescription opioids only, 8.1% had a claim for both MOUD and prescription opioids, and 39.1% did not have a claim for MOUD or prescription opioids in pregnancy. Non-Hispanic Black women were less likely to have a claim for MOUD than non-Hispanic White women. The percentage of infants born full term and normal birth weight was highest among women with MOUD or both MOUD and prescription opioid claims. Conclusions. In the 2016-2018 NC Medicaid population, 60% of mothers of infants with NOWS had MOUD or prescription opioid claims in pregnancy, underscoring the extent to which cases of NOWS may be a result of medically appropriate opioid use in pregnancy.

In this study, we examined the factors influencing enrollment in early intervention (EI) programs for neonates diagnosed with nonopioid-associated neonatal abstinence syndrome (NAS) and neonatal opioid withdrawal syndrome (NOWS). The primary goal was to examine characteristics linked to completing an individualized family service plan (IFSP), marking EI enrollment. Patient records were reviewed using data from neonates discharged with NOWS/NAS at a Massachusetts hospital in 2017 to identify demographic and medical factors related to NOWS/NAS cases. Out of 125 cases, 111 were analyzed, with patient outcomes analyzed in subgroups of those with NOWS and non-opioid-associated NAS. Findings indicated that neonates with NICU hospitalization, race, payor, and maternal medication for opioid use disorder (MOUD) did not have significantly different rates of IFSP completion. Additionally, no significant difference was observed in IFSP completion rates between neonates with NAS or NOWS. This study reports baseline data from a quality improvement initiative not designed to detect statistically significant differences. However, it highlights potential areas for further investigation to improve EI access for NOWS- and NAS-affected neonates, although more extensive studies are needed to further elucidate these differences.

Purpose: To evaluate Neonatal Opioid Withdrawal Syndrome (NOWS) pre and post COVID-19 pandemic in a comprehensive perinatal substance treatment program. Methods: Prospective cohort study of pregnant patients with OUD enrolled in a multidisciplinary treatment program between January 2015 and July 2023. 404 patients were delivered prior to the COVID-19 pandemic (January 2015- December 2019) while 277 patients delivered during the pandemic (January 2020-July 2023). Primary outcomes assessed were NOWS and length of treatment. Secondary outcomes included maternal psychosocial data, engagement with PNC, and obstetric outcomes. Fisher’s Exact test and two-sample t-tests were utilized for analysis. Results: 681 total patients with OUD were analyzed. Comparisons are pre-pandemic v post-pandemic. Maternal age was 28.9 +/- 4.7 v 29.7 +/- 5.1 years, p=.045. There was no significant difference in race or tobacco use between the groups. Psychiatric disorders were more common during the COVID pandemic including anxiety 52.6 v 70.2% p<.0001, bipolar 12.3 v 20.6% p=.0073, panic disorder 1.4 v 6.1% p=.0028, PTSD 6 v 28.9% p<.0001, and depression 58.9 v. 65.8% p=.099. Pregnant persons experienced more IPV during COVID based on positive AAS score 43.8% v 62.9%, p=.0001. There was a significant difference in utilization of medication for opioid use disorder (MOUD) at enrollment with buprenorphine 94.4 v 64.9% and no MOUD 4.8 v 31.7% p<0001. Patients were less likely to be on buprenorphine products as their chosen treatment at both enrollment and delivery timepoints in the post Covid era (p< 0.0001). Prenatal visits were also decreased during the COVID pandemic 11.5 +/- 7.1 v 9.6+/- 7.5, p=.0009. There was no significant difference in GA at delivery. Treatment for NOWS was significantly higher during COVID 37.7% v 53.5%, p=.0007, as was days of treatment for NOWS 15.0 +/- 9.5 v 20.7 +/- 11.3, p= .0001. Breast feeding also decreased during COVID, 23% v 9.1%, p=.0001. Conclusions: NOWS was significantly higher during the COVID pandemic despite a decrease in MOUD utilization. This is likely due to multiple factors (multifactorial) including less utilization of non-pharmacologic interventions such as “Eat, Sleep, Console” and breastfeeding at our institution during the pandemic.

The aim of this study was to identify distinct trajectories of prescription opioid exposure in pregnancy-encompassing both medication for opioid use disorder (MOUD) and opioid analgesics-and explore their associations with birth outcomes. Trajectories were identified using latent class analysis among Wisconsin Medicaid-insured live births 2011-2019. Logistic regression estimated associations between these trajectories and neonatal opioid withdrawal syndrome (NOWS), small for gestational age, preterm birth, birth weight, and gestational age. Of 138,123 births, 27,293 (19.8%) had prenatal opioid exposure. Five trajectory classes were identified: (1) stable MOUD treatment (5.8%), (2) inconsistent MOUD treatment (3.9%), (3) chronic analgesic use (4.2%), (4) intermittent analgesic use (7.8%), and (5) low-level use of MOUD and analgesics (78.3%). NOWS incidence per 1000 infants was 667 for class 1 (adjusted odds ratio [aOR]: 21.74, 95% confidence interval [CI]: 17.89, 26.41), 570 for class 2 (aOR: 15.35, 95% CI: 12.49, 18.87), 235 for class 3 (aOR: 19.42, 95% CI: 15.93, 23.68), 67 for class 4 (aOR: 6.23, 95% CI: 4.99, 7.76), and 12 for class 5 (aOR: 1.73, 95% CI: 1.47, 2.02). Classes 1-4 had elevated risk of small for gestational age, preterm birth, lower birth weight, and shorter gestational age, with no significant differences among these classes. Among individuals with opioid use disorder, stable MOUD treatment was associated with higher birth weights and longer gestational ages compared to inconsistent treatment, despite higher odds of NOWS. Early initiation and consistent MOUD treatment may improve birth weight and gestational age. For pregnant individuals with opioid use disorder using chronic analgesics, transition to MOUD may promote birth outcomes.

Treatment of Neonatal Opioid Withdrawal.

State Medicaid programs are the largest single provider of healthcare for pregnant persons with opioid use disorder (OUD). Our objective was to provide comparable, multistate measures estimating the burden of OUD in pregnancy, medication for OUD (MOUD) in pregnancy, and related neonatal and child outcomes. Drawing on the Medicaid Outcomes Distributed Research Network (MODRN), we accessed administrative healthcare data for 1.6 million pregnancies and 1.3 million live births in 9 state Medicaid populations from 2014 to 2017. We analyzed within- and between-state prevalences and time trends in the following outcomes: diagnosis of OUD in pregnancy, initiation, and continuity of MOUD in pregnancy, Neonatal Opioid Withdrawal Syndrome (NOWS), and well-child visit utilization among children with NOWS. OUD diagnosis increased from 49.6 per 1000 to 54.1 per 1000 pregnancies, and the percentage of those with any MOUD in pregnancy increased from 53.4% to 57.9%, during our study time period. State-specific percentages of 180-day continuity of MOUD ranged from 41.2% to 84.5%. The rate of neonates diagnosed with NOWS increased from 32.7 to 37.0 per 1000 live births. State-specific percentages of children diagnosed with NOWS who had the recommended well-child visits in the first 15 months ranged from 39.3% to 62.5%. Medicaid data, which allow for longitudinal surveillance of care across different settings, can be used to monitor OUD and related pregnancy and child health outcomes. Findings highlight the need for public health efforts to improve care for pregnant persons and children affected by OUD.

Delivery dose of methadone, but not buprenorphine, is associated with the risk and severity of neonatal opiate withdrawal syndrome

In recent years, there has been a sixfold increase in the number of pregnant people with opioid use disorder (OUD). Rates of neonatal opioid withdrawal syndrome (NOWS), previously known as neonatal abstinence syndrome (NAS), have significantly increased in virtually every state and demographic group(HealthcareCostUtilizationProject,HCUP,2010). NOWS is a condition resulting from chronic exposure to either therapeutic opioid use (e.g., medication for OUD, chronic pain conditions) or nonprescribed opioid use. To date, there is no known prenatal treatment to help decrease the risk of infants developing NOWS and subsequent neurodevelopmental outcomes. Given the increasing support for how placental signaling, or placental programming, may play a role in downstream pathology, prospective research investigating how the placenta is affected by chronic opioid exposure morphologically, histologically, and at the cellular level may open up potential treatment opportunities in this field. In this review, we discuss literature exploring the physiological roles of nitric oxide and dopamine not only in the vascular development of the placenta, but also in fetal cerebral blood flow, neurogenesis, neuronal differentiation, and neuronal activity. We also discuss histological preclinical studies that suggest chronic opioid exposure to induce some combination of placental dysfunction and hypoxia in a manner similar to other well-known placental pathologies, as denoted by the compensatory neovascularization and increased utilization of the placenta's supply of trophoblast cells, which play an essential role in placental angiogenesis. Overall, we found that the current literature, while limited, suggests chronic opioid exposure negatively impacts placental function and fetal brain development on a cellular and histopathological level. We conclude that it is worthwhile to consider the placenta as a therapeutic target with the ultimate goal of decreasing the incidence of NOWS and the long-term impacts of prenatal opioid exposure.

Although medications for opioid use disorder improve both maternal and neonatal outcomes, little is known about opioid-exposed infants born during episodes of incarceration. The study sought to examine birth outcomes for infants born with opioid exposure during perinatal incarceration. Participants were identified from clinic rosters in a Southeastern women's prison (2016-2019). Included infants born to pregnant people with opioid use disorder incarcerated in the study facility at the time of delivery. We abstracted hospital length of stay, neonatal opioid withdrawal syndrome (NOWS) severity, and discharge plan from hospital records and report descriptive statistics, analysis of variance F tests, and chi-square tests to compare outcomes by opioid exposure type. There were 125 infants born after exposure to methadone (n = 34), buprenorphine (n = 15), oxycodone (n = 22), or no opioid medication (n = 54) during prenatal incarceration. Most infants exposed to methadone or buprenorphine had difficulty with eating, sleeping, or consoling (97% and 80%), and 59% and 47% were treated with medication for NOWS, respectively. The majority with prenatal opioid exposure required intervention for NOWS symptoms after their birthing parent was discharged to the prison. The average hospital length of stay was different for infants with no opioid, methadone, buprenorphine, and oxycodone exposure during incarceration (4, 15, 12, and 9 days, respectively, P < 0.001). Neonatal hospitalization experiences of infants with perinatal opioid exposures during maternal incarceration mirror those of similarly exposed infants born outside the context of incarceration, except for hospital length of stay. Consideration of avoiding separation of the parent-infant dyad may be needed to improve outcomes for these infants.

Prenatal opioid exposure (POE) is commonly associated with neonatal opioid withdrawal syndrome (NOWS), which is characterized by a broad variability in symptoms and severity. Currently there are no diagnostic tools to reliably predict which infants will develop severe NOWS, while risk stratification would allow for proactive decisions about appropriate clinical monitoring and interventions. The aim of this prospective cohort study was to assess if extracellular microRNAs (miRNAs) in umbilical cord plasma of infants with POE could predict NOWS severity. Participants (n = 58) consisted of pregnant women receiving medications for opioid use disorder and their infants. NOWS severity was operationalized as the need for pharmacologic treatment and prolonged hospitalization (≥ 14 days). Cord blood miRNAs were assessed using semi-quantitative qRT-PCR arrays. Receiver operating characteristic curves and area under the curve (AUC) were estimated. The expression of three miRNAs (miR-128-3p, miR-30c-5p, miR-421) predicted need for pharmacologic treatment (AUC: 0.85) and prolonged hospitalization (AUC: 0.90). Predictive validity improved after two miRNAs (let-7d-5p, miR-584-5p) were added to the need for pharmacologic treatment model (AUC: 0.94) and another two miRNAs (let-7b-5p, miR-10-5p) to the prolonged hospitalization model (AUC: 0.99). Infant cord blood extracellular miRNAs can proactively identify opioid-exposed neonates at high-risk for developing severe NOWS.