The ultrasonic vocalization (USV) syllable profile during neonatal opioid withdrawal and a kappa opioid receptor component to increased USV emissions in female mice.

RATIONALE: Opioid use during pregnancy can lead to negative infant health outcomes, including neonatal opioid withdrawal syndrome (NOWS). NOWS comprises gastrointestinal, autonomic nervous system, and neurological dysfunction that manifest during spontaneous withdrawal. Variability in NOWS severity necessitates a more individualized treatment approach. Ultrasonic vocalizations (USVs) in neonatal mice are emitted in isolation as a stress response and are increased during opioid withdrawal, thus modeling a negative affective state that can be utilized to test new treatments. OBJECTIVES: We sought to identify the behavioral and USV profile, brainstem transcriptomic adaptations, and role of kappa opioid receptors in USVs during neonatal opioid withdrawal. METHODS: We employed a third trimester-approximate opioid exposure model, where neonatal inbred FVB/NJ pups were injected twice-daily with morphine (10mg/kg, s.c.) or saline (0.9%, 20 ul/g, s.c.) from postnatal day(P) 1 to P14. This protocol induces reduced weight gain, hypothermia, thermal hyperalgesia, and increased USVs during spontaneous morphine withdrawal. RESULTS: On P14, there were increased USV emissions and altered USV syllables during withdrawal, including an increase in Complex 3 syllables in FVB/NJ females (but not males). Brainstem bulk mRNA sequencing revealed an upregulation of the kappa opioid receptor (Oprk1), which contributes to withdrawal-induced dysphoria. The kappa opioid receptor (KOR) antagonist, nor-BNI (30 mg/kg, s.c.), significantly reduced USVs in FVB/NJ females, but not males during spontaneous morphine withdrawal. Furthermore, the KOR agonist, U50,488h (0.625 mg/kg, s.c.), was sufficient to increase USVs on P10 (both sexes) and P14 (females only) in FVB/NJ mice. CONCLUSIONS: We identified an elevated USV syllable, Complex 3, and a female-specific recruitment of the dynorphin/KOR system in increased USVs associated with neonatal opioid withdrawal severity.

Trauma Prevalence and Its Association With Health-Related Quality of Life in Pregnant Persons with Opioid Use Disorder.

OBJECTIVES: Trauma screening is recommended for pregnant persons with opioid use disorder (OUD), but there is limited literature on screening results from buprenorphine treatment. This study's objectives were to 1) describe the types, and severity, of traumatic events reported and 2) evaluate the associations between trauma and health-related quality of life (HRQoL). METHODS: Baseline data from an ongoing trial were analyzed. Participants were 155 pregnant persons with OUD receiving, or enrolling in, buprenorphine treatment at one of 13 sites. The experience, and relative severity, of 14 high magnitude stressors were assessed with the trauma history screen. The Patient-Reported Outcomes Measurement Information System-29+2 was used to assess 8 HRQoL domains. RESULTS: Traumatic stressors were reported by 91% of the sample (n = 155), with 54.8% reporting a lifetime persisting posttraumatic distress (PPD) event and 29.7% reporting a childhood PPD event. The most prevalent lifetime PPD event was sudden death of a close family/friend (25.8%); physical abuse was the most prevalent childhood PPD event (10.3%). Participants with lifetime PPD, relative to no PPD, reported significantly greater pain interference (P = 0.02). Participants with childhood PPD, relative to no PPD, had significantly worse HRQoL overall (P = 0.01), and worse pain intensity (P = 0.002), anxiety (P = 0.003), depression (P = 0.007), fatigue (P = 0.002), and pain interference (P < 0.001). CONCLUSIONS: A majority of pregnant persons enrolled/enrolling in buprenorphine treatment reported persisting posttraumatic distress with sudden death of close family/friend being the most prevalent originating event; clinicians should consider the impact that the opioid-overdose epidemic may be having in increasing trauma exposure in patients with OUD.

Racial and ethnic disparities in testing of Hepatitis C virus-exposed children across the United States.

BACKGROUND: Despite rising hepatitis C virus (HCV) prevalence among pregnant individuals in the United States, HCV testing among exposed infants remains low. Although recent guidelines recommend early RNA testing for HCV-exposed children to help improve testing rates, national studies describing factors associated with HCV testing and type of testing completed are lacking. METHODS: In this retrospective national study, we characterized HCV testing and care among HCV-exposed infants born 2010-2020 captured in the electronic health record-based TriNetX Research Network. We analyzed factors associated with appropriate HCV testing completion (negative or positive HCV RNA testing or negative HCV antibody testing at any age through study end in 2022) and with RNA compared with antibody testing, using univariable and multivariable logistic regression with clustered standard errors by healthcare organization. RESULTS: Of 8,516 HCV-exposed children, 45.8% completed any HCV testing and 42.1% completed appropriate testing (25% of whom had RNA testing only). 182 (5.1% of appropriately tested children) had evidence of HCV infection. Of 104 treatment-eligible children, 14.4% were treated. Black (OR 0.38, 95% CI 0.26-0.55), Asian/Pacific Islander (OR 0.06, 95% CI 0.03-0.11), and Hispanic/Latinx children (OR 0.56, 95% CI 0.36-0.88) had lower odds of appropriate testing compared with White and non-Hispanic/Latinx children, respectively. CONCLUSIONS: Fewer than half of HCV-exposed children in this national sample were tested for HCV, with lower testing odds among Black, Asian/Pacific Islander, and Hispanic/Latinx children. Substantial work to increase testing and treatment and decrease disparities in testing among HCV-exposed children is needed to help reach US HCV elimination goals.

The ultrasonic vocalization (USV) syllable profile during neonatal opioid withdrawal and a kappa opioid receptor component to increased USV emissions in female mice.

Rationale: Opioid use during pregnancy can lead to negative infant health outcomes, including neonatal opioid withdrawal syndrome (NOWS). NOWS comprises gastrointestinal, autonomic nervous system, and neurological dysfunction that manifest during spontaneous withdrawal. Variability in NOWS severity necessitates a more individualized treatment approach. Ultrasonic vocalizations (USVs) in neonatal mice are emitted in isolation as a stress response and are increased during opioid withdrawal, thus modeling a negative affective state that can be utilized to test new treatments. Objectives: We sought to identify the behavioral and USV profile, brainstem transcriptomic adaptations, and role of kappa opioid receptors in USVs during neonatal opioid withdrawal. Methods: We employed a third trimester-approximate opioid exposure model, where neonatal inbred FVB/NJ pups were injected twice-daily with morphine (10mg/kg, s.c.) or saline (0.9%, 20 ul/g, s.c.) from postnatal day(P) 1 to P14. This protocol induces reduced weight gain, hypothermia, thermal hyperalgesia, and increased USVs during spontaneous morphine withdrawal. Results: On P14, there were increased USV emissions and altered USV syllables during withdrawal, including an increase in Complex 3 syllables in FVB/NJ females (but not males). Brainstem bulk mRNA sequencing revealed an upregulation of the kappa opioid receptor (Oprk1), which contributes to withdrawal-induced dysphoria. The kappa opioid receptor (KOR) antagonist, nor-BNI (30 mg/kg, s.c.), significantly reduced USVs in FVB/NJ females, but not males during spontaneous morphine withdrawal. Furthermore, the KOR agonist, U50,488h (0.625 mg/kg, s.c.), was sufficient to increase USVs on P10 (both sexes) and P14 (females only) in FVB/NJ mice. Conclusions: We identified an elevated USV syllable, Complex 3, and a female-specific recruitment of the dynorphin/KOR system in increased USVs associated with neonatal opioid withdrawal severity.

Mandatory Child Protective Services Reporting for Substance-Exposed Newborns and Peripartum Outcomes: A Difference-in-Differences Analysis.

This cross-sectional study examines data across 17 birthing hospitals before and after a policy change at Boston Medical Center in how reporting decisions are made in cases of prenatal substance exposure.

Neurobehavioral outcomes of infants exposed to buprenorphine-naloxone compared with naltrexone during pregnancy.

BACKGROUND: Naltrexone is a medication used to treat both opioid and alcohol use disorder with limited experience in pregnant individuals, particularly in comparison to more commonly utilized treatments such as buprenorphine-naloxone. The long-term outcomes of infants exposed to naltrexone has not been previously examined. AIMS: To compare the neurobehavioral outcomes of naltrexone versus buprenorphine-naloxone exposed infants. STUDY DESIGN: Multi-centered prospective cohort study. SUBJECTS: Pregnant people on prescribed buprenorphine-naloxone or naltrexone were enrolled during pregnancy and the dyad followed until 12 months after delivery. OUTCOME MEASURES: Infants were evaluated at 4-6 weeks corrected gestational age (CGA) using the NICU Neonatal Neurobehavioral Scale (NNNS) and at the 12-month CGA visit using the Ages and Stages Questionnaire, Third Edition (ASQ-3). RESULTS: There were 7 dyads in the naltrexone group and 34 in the buprenorphine-naloxone group. On the NNNS, infants exposed to naltrexone had higher median scores for arousal and excitability, and lower median scores for attention and regulation at 4-6 weeks CGA compared to the buprenorphine-naloxone group. None of the infants in the naltrexone group were monitored for NOWS and had shorter length of hospital stay compared with the buprenorphine-naloxone group. Although no statistically significant differences were observed, more infants in the buprenorphine-naloxone group were identified as at risk for development delays in the communication, problem solving, and personal social domains of the ASQ-3 at 12 months CGA. Results should be interpreted with caution given this study's small sample size and lack of a prospective comparison cohort. CONCLUSIONS: In this small cohort, there are differences noted in infant neurobehavior by NNNS at 4-6 weeks of age when comparing the buprenorphine-naloxone and naltrexone groups. At 12 months, ASQ-3 scores were similar but with percentage differences in potential development delay risk observed between the two groups. Larger cohort studies are needed to determine the long-term child outcomes after naltrexone exposure in pregnancy.

Short term outcomes of neonatal opioid withdrawal syndrome: a comparison of two approaches.

OBJECTIVE: To evaluate outcomes in opioid exposed neonates (OENs) assessed by the Eat, Sleep, Console (ESC) tool compared to the Finnegan Neonatal Abstinence Scoring System (FNASS). METHODS: Retrospective analysis of a statewide database of OENs from 2017 to 2020 with birthing hospitals classified based on the assessment tool used. Four main outcomes were examined using multivariable and Poisson logistic regression models. RESULTS: Of 2375 OENs, 42.1% received pharmacotherapy (PT) with a consistent decrease in PT, length of treatment (LOT), and length of stay (LOS) over the study period. There was no change in use of mother's own milk (MoM). While outcomes were significantly associated with several specific variables, there were no differences in outcomes between assessment methods. CONCLUSION: While there was a significant decrease over time in PT, LOT, and LOS, improvements were independent of the assessment tool used and likely related to the increased use of non-pharmacologic care.

Case Series of Individuals Treated With Naltrexone During Pregnancy for Opioid and/or Alcohol Use Disorder.

OBJECTIVE: There is a lack of knowledge about the relative safety and efficacy of naltrexone for the treatment of pregnant individuals with opioid and/or alcohol use disorder, including the range of outcomes, in both the pregnant individual and the infant, over the course of peripartum period. Our objective was to describe these outcomes in a cohort of pregnant individuals on naltrexone. METHODS: In this prospective case series, 7 pregnant individuals with opioid use disorder (OUD) or alcohol use disorder (AUD) treated with naltrexone were followed from pregnancy through 12 months after delivery. Clinical treatment protocols and outcomes related to safety and efficacy during pregnancy, delivery, and the postpartum period are described. RESULTS: There were 4 pregnant individuals with OUD and 3 with AUD, of which 3 were managed with oral and 4 with extended-release naltrexone. The mean gestational age at study enrollment was 21.7 (SD, 12) weeks. Of the 7 participants, there was no return to nonprescribed opioid use and 2 who experienced a return to alcohol use over the course of the study. All individuals delivered vaginally at a mean of 37 weeks gestation without any peripartum pain difficulties. Five of the individuals (71.4%) remained on naltrexone 12 months after delivery. There were no reported fetal anomalies and one preterm delivery. None of the infants developed neonatal opioid withdrawal syndrome. CONCLUSIONS: For pregnant individuals with OUD or AUD treated with naltrexone, there were low rates of return to nonprescribed use and reassuring pregnant person and infant outcomes to 12 months postpartum.

Trimester and severity of SARS-CoV-2 infection during pregnancy and risk of hypertensive disorders in pregnancy.

OBJECTIVE: SARS-CoV-2 infection during pregnancy has been linked with an increased risk of hypertensive disorders of pregnancy (HDP). The aim of this study was to examine how both trimester and severity of SARS-CoV-2 infection impact HDP. METHODS: We conducted a cohort study of SARS-CoV-2-infected individuals during pregnancy (n = 205) and examined the association between trimester and severity of infection with incidence of HDP using modified Poisson regression models to calculate risk ratios (RR) and 95% confidence intervals (CI). We stratified the analysis of trimester by severity to understand the role of timing of infection among those with similar symptomatology and also examined timing of infection as a continuous variable. RESULTS: Compared to a reference cohort from 2018, SARS-CoV-2 infection did not largely increase the risk of HDP (RR: 1.17; CI:0.90, 1.51), but a non-statistically significant higher risk of preeclampsia was observed (RR: 1.33; CI:0.89, 1.98), in our small sample. Among the SARS-CoV-2 cohort, severity was linked with risk of HDP, with infections requiring hospitalization increasing the risk of HDP compared to asymptomatic/mild infections. Trimester of infection was not associated with risk of HDP, but a slight decline in the risk of HDP was observed with later gestational week of infection. Among patients with asymptomatic or mild symptoms, SARS-CoV-2 in the first trimester conferred a higher risk of HDP compared to the third trimester (RR: 1.70; CI:0.77, 3.77), although estimates were imprecise. CONCLUSION: SARS-CoV-2 infection in early pregnancy may increase the risk of HDP compared to infection later in pregnancy.

Advances in the Care of Infants With Prenatal Opioid Exposure and Neonatal Opioid Withdrawal Syndrome.

A significant number of advances have been made in the last 5 years with respect to the identification, diagnosis, assessment, and management of infants with prenatal opioid exposure and neonatal opioid withdrawal syndrome (NOWS) from birth to early childhood. The primary objective of this review is to summarize major advances that will inform the clinical management of opioid-exposed newborns and provide an overview of NOWS care to promote the implementation of best practices. First, advances with respect to standardizing the clinical diagnosis of NOWS will be reviewed. Second, the most commonly used assessment strategies are discussed, with a focus on presenting new quality improvement and clinical trial data surrounding the use of the new function-based assessment Eat, Sleep, and Console approach. Third, both nonpharmacologic and pharmacologic treatment modalities are reviewed, highlighting clinical trials that have compared the use of higher calorie and low lactose formula, vibrating crib mattresses, morphine compared with methadone, buprenorphine compared with morphine or methadone, the use of ondansetron as a medication to prevent the need for NOWS opioid pharmacologic treatment, and the introduction of symptom-triggered dosing compared with scheduled dosing. Fourth, maternal, infant, environmental, and genetic factors that have been found to be associated with NOWS severity are highlighted. Finally, emerging recommendations on postdelivery hospitalization follow-up and developmental surveillance are presented, along with highlighting ongoing and needed areas of research to promote infant and family well-being for families impacted by opioid use.

Hair Cortisol Concentrations in Opioid-Exposed versus Nonexposed Mother-Infant Dyads.

OBJECTIVE: To pilot measurement of hair cortisol concentration (HCC) in pregnant women with opioid use disorder and their infants over time and study the potential utility of hair cortisol as a biomarker of chronic stress in this population. STUDY DESIGN: In this pilot prospective cohort study of mother-infant dyads with and without prenatal opioid exposure, we obtained mother-infant HCCs at delivery and again within 1 to 3 months' postpartum. HCCs were compared between the opioid and control groups and between the two time points. RESULTS: There were no significant differences between opioid and control group maternal or infant HCCs at either time point. However, within the opioid-exposed group, there was a significant increase in infant HCCs across the two time points. CONCLUSION: This pilot study describes our experience with the measurement of HCCs in opioid-exposed mother-infant dyads. KEY POINTS: · Maternal stress impacts fetal and child health.. · Many stressors in pregnant women with opioid use disorder.. · Hair cortisol may be a useful stress biomarker..

National Provider Survey: Use of Naltrexone for Pregnant Individuals with Substance Use Disorders.

OBJECTIVES: A national survey evaluated the availability of naltrexone as a treatment for alcohol use disorder and/or opioid use disorder for pregnant individuals. Provider perceptions of barriers to treatment with naltrexone during pregnancy were also examined. METHODS: Sites were selected from a national registry of naltrexone prescribers (N = 5208). A 10% sampling of sites within 150 miles of each state's capital was selected (n = 2073). Survey of 11 questions included availability of naltrexone for pregnant individuals, standard practices for treating pregnant individuals already on naltrexone, and barriers to treatment. Survey responses were summarized to identify top barriers and national trends in service availability. RESULTS: Of the 236 sites contacted, 78 (33.1%) completed the survey. There was significant geographic variation in number of available sites, with Northeast United States having the most sites. Of the 78 responding sites, only 23 (35.9%) offered naltrexone for pregnant individuals. The most common barriers to prescribing naltrexone included the following: sites without pregnant patients (15.6%), lack of national guidelines in using naltrexone for pregnant patients (14.1%), providers' discomfort with prescribing naltrexone during pregnancy due to safety concerns (9.4%), and providers' discomfort due to inexperience (4.7%). CONCLUSIONS: Accessibility of naltrexone and related care for pregnant individuals with alcohol use disorder and opioid use disorder varies greatly across the United States with numerous barriers and educational gaps identified. Additional research and resources are needed to expand naltrexone treatment access for pregnant individuals.

Academy of Breastfeeding Medicine Clinical Protocol #21: Breastfeeding in the Setting of Substance Use and Substance Use Disorder (Revised 2023).

Background: The Academy of Breastfeeding Medicine (ABM) revised the 2015 version of the substance use disorder (SUD) clinical protocol to review the evidence and provide updated literature-based recommendations related to breastfeeding in the setting of substance use and SUD treatments. Key Information: Decisions around breastfeeding are an important aspect of care during the peripartum period, and there are specific benefits and risks for substance-exposed mother-infant dyads. Recommendations: This protocol provides breastfeeding recommendations in the setting of nonprescribed opioid, stimulant, sedative-hypnotic, alcohol, nicotine, and cannabis use, and SUD treatments. Additionally, we offer guidance on the utility of toxicology testing in breastfeeding recommendations. Individual programs and institutions should establish consistent breastfeeding approaches that mitigate bias, facilitate consistency, and empower mothers with SUD. For specific breastfeeding recommendations, given the complexity of breastfeeding in mothers with SUD, individualized care plans should be created in partnership with the patient and multidisciplinary team with appropriate clinical support and follow-up. In general, breastfeeding is recommended among mothers who stop nonprescribed substance use by the time of delivery, and they should continue to receive ongoing postpartum care, such as lactation support and SUD treatment. Overall, enhancing breastfeeding education regarding substance use in pregnancy and lactation is essential to allow for patient-centered guidance.

Ultrasound evaluation of brain parenchyma in preterm infants with prenatal opioid exposure.

OBJECTIVE: To evaluate whether preterm infants with prenatal opioid exposure had differences in brain size on head ultrasounds (HUS) in comparison to non-exposed infants. STUDY DESIGN: Preterm infants ≤34 weeks with prenatal opioid exposure (n = 47) and matched non-exposed infants (n = 62) with early HUSs were examined. Fifteen brain measurements were made and linear regression models performed to evaluate differences. RESULTS: Brain measurements were smaller in the right ventricular index [ß = -0.18 mm (95% CI -0.32, -0.03]), left ventricular index [ß = -0.04 mm (95% CI -0.08, -0.003)], left basal ganglia insula [ß = -0.10 mm (95% CI -0.15, -0.04)], right basal ganglia insula [ß = -0.08 mm (95% CI -0.14, -0.03)], corpus callosum fastigium length [ß = -0.16 mm (95% CI -0.25, -0.06)], intracranial height index [ß = -0.31 mm (95% CI -0.44, -0.18)], and transcerebellar measurements [ß = -0.13 (95% CI -0.25, -0.02)] in the opioid-exposed group. CONCLUSIONS: Preterm infants with prenatal opioid exposure have smaller brain sizes compared to non-exposed infants, potentially increasing their risk for neurodevelopmental abnormalities.

Comparison of Anti-SARS-CoV-2-Specific Antibody Signatures in Maternal and Infant Blood after COVID-19 Infection versus COVID-19 Vaccination during Pregnancy.

OBJECTIVE: The Advisory Committee on Immunization Practices and The American College of Obstetricians and Gynecologists recommend coronavirus disease 2019 (COVID-19) vaccine for pregnant persons to prevent severe illness and death. The objective was to examine levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG, IgM, and IgA against spike protein receptor binding domain (RBD) and nucleocapsid protein (NCP) in maternal and infant/cord blood at delivery after COVID 19 vaccination compared with SARS-CoV-2 infection at in mother-infant dyads at specified time points. STUDY DESIGN: Mothers with SARS-CoV-2 infection (n = 31) or COVID-19 vaccination (n = 25) during pregnancy were enrolled between July 2020 and November 2021. Samples were collected at delivery and IgG, IgM, and IgA to RBD of spike and NCPs compared in the infected and vaccinated groups. Timing of infection/vaccination prior to delivery and correlation with antibody levels was performed. RESULTS: The majority of participants received vaccination within 90 days of delivery and over half received the Pfizer BioNTech vaccine. There were no significant correlations between antibody levels and timing of infection or vaccination. Infant IgG levels to the RBD domain of spike protein were higher in the vaccinated group (n = 25) as compared with the infants born to mothers with infection (n = 31). Vaccination against COVID-19 during pregnancy was associated with detectable maternal and infant anti-RBD IgG levels at delivery irrespective of the timing of vaccination. CONCLUSION: Timing of vaccination had no correlation to the antibody levels suggesting that the timing of maternal vaccination in the cohort did not matter. There was no IgM detected in infants from vaccinated mothers. Infants from vaccinated mothers had robust IgG titers to RBD, which have a lasting protective effect in infants. KEY POINTS: · COVID-19 vaccination during pregnancy had detectable antibody.. · No correlation between antibody levels and timing of vaccination.. · Infants from vaccinated mothers had robust IgG titers to RBD..

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.

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. HIGHLIGHTS: We replicated some NOWS model traits via 1x-daily morphine (P1-P14).We found a downregulation of myelination genes in nucleus accumbens on P15.There were no effects on learning/memory or reward sensitivity in adults.

Drivers of decision-making regarding infant sleep practices among mothers with opioid use disorder.

OBJECTIVE: To understand the perspectives and perceived facilitators of and barriers to following safe infant sleeping practices among mothers with opioid use disorder (OUD). STUDY DESIGN: Using the Theory of Planned Behavior (TPB) framework, we conducted qualitative interviews with mothers with OUD regarding infant sleep practices. We created codes and generated themes, concluding data collection upon achieving thematic saturation. RESULTS: Twenty-three mothers with infants 1-7 months of age were interviewed from 08/2020 to 10/2021. Mothers chose sleeping practices they perceived made their infants safer, more comfortable, and minimized infant withdrawal symptoms. Mothers in residential treatment facilities were influenced by facility infant sleep rules. Hospital sleep modeling and varied advice by providers, friends and family influenced maternal decisions. CONCLUSIONS: Mothers reported factors unique to their experience with OUD that influenced their decisions about infant sleep that should be considered when developing tailored interventions to promote safe infant sleep in this population.

Medication for Opioid Use Disorder During Pregnancy - Maternal and Infant Network to Understand Outcomes Associated with Use of Medication for Opioid Use Disorder During Pregnancy (MAT-LINK), 2014-2021.

Problem: Medication for opioid use disorder (MOUD) is recommended for persons with opioid use disorder (OUD) during pregnancy. However, knowledge gaps exist about best practices for management of OUD during pregnancy and these data are needed to guide clinical care. Period Covered: 2014-2021. Description of the System: Established in 2019, the Maternal and Infant Network to Understand Outcomes Associated with Medication for Opioid Use Disorder During Pregnancy (MAT-LINK) is a surveillance network of seven clinical sites in the United States. Boston Medical Center, Kaiser Permanente Northwest, The Ohio State University, and the University of Utah were the initial clinical sites in 2019. In 2021, three clinical sites were added to the network (the University of New Mexico, the University of Rochester, and the University of South Florida). Persons receiving care at the seven clinical sites are diverse in terms of geography, urbanicity, race and ethnicity, insurance coverage, and type of MOUD received. The goal of MAT-LINK is to capture demographic and clinical information about persons with OUD during pregnancy to better understand the effect of MOUD on outcomes and, ultimately, provide information for clinical care and public health interventions for this population. MAT-LINK maintains strict confidentiality through robust information technology architecture. MAT-LINK surveillance methods, population characteristics, and evaluation findings are described in this inaugural surveillance report. This report is the first to describe the system, presenting detailed information on funding, structure, data elements, and methods as well as findings from a surveillance evaluation. The findings presented in this report are limited to selected demographic characteristics of pregnant persons overall and by MOUD treatment status. Clinical and outcome data are not included because data collection and cleaning have not been completed; initial analyses of clinical and outcome data will begin in 2023. Results: The MAT-LINK surveillance network gathered data on 5,541 reported pregnancies with a known pregnancy outcome during 2014-2021 among persons with OUD from seven clinical sites. The mean maternal age was 29.7 (SD = ±5.1) years. By race and ethnicity, 86.3% of pregnant persons were identified as White, 25.4% as Hispanic or Latino, and 5.8% as Black or African American. Among pregnant persons, 81.6% had public insurance, and 84.4% lived in urban areas. Compared with persons not receiving MOUD during pregnancy, those receiving MOUD during pregnancy were more likely to be older and White and to have public insurance. The evaluation of the surveillance system found that the initial four clinical sites were not representative of demographics of the South or Southwest regions of the United States and had low representation from certain racial and ethnic groups compared with the overall U.S. population; however, the addition of three clinical sites in 2021 made the surveillance network more representative. Automated extraction and processing improved the speed of data collection and analysis. The ability to add new clinical sites and variables demonstrated the flexibility of MAT-LINK. Interpretation: MAT-LINK is the first surveillance system to collect comprehensive, longitudinal data on pregnant person-infant dyads with perinatal outcomes associated with MOUD during pregnancy from multiple clinical sites. Analyses of clinical site data demonstrated different sociodemographic characteristics between the MOUD and non-MOUD treatment groups. Public Health Actions: MAT-LINK is a timely and flexible surveillance system with data on approximately 5,500 pregnancies. Ongoing data collection and analyses of these data will provide information to support clinical and public health guidance to improve health outcomes among pregnant persons with OUD and their children.