Gestational buprenorphine-naloxone exposure and fetal neurobehavior.

BACKGROUND: Buprenorphine-naloxone treatment may confer substantial benefits for the treatment of opioid use disorder (OUD) during pregnancy including lower risk for overdose/death, less diversion potential and reduced use of other substances. Treatment may also result in less severe Neonatal Abstinence Syndrome (NAS), but little is known about the effects of this medication on fetal neurodevelopment. METHODS: The purpose of the current study is to evaluate neurobehaviors among fetuses exposed to buprenorphine-naloxone at four time points over the second and third trimesters of gestation in pregnant women with OUD on buprenorphine-naloxone therapy. Sixty minutes of continuous fetal monitoring via fetal actocardiograph with a single wide array abdominal transducer took place at times of peak and trough buprenorphine-naloxone levels in 24 pregnant women. Data collection, which included measures of fetal heart rate and motor activity, was conducted between 24 and 36 weeks gestation, with the majority (84.6%) monitored at two or more gestational ages. Medication dose and other substance use was monitored throughout the study and infant NAS severity was assessed. RESULTS: Fetal heart rate (FHR), FHR variability, accelerations in FHR, and motor activity were suppressed when buprenorphine-naloxone levels were at pharmacologic peak as compared to trough concentrations at 36 weeks, but not earlier in gestation. Maternal medication dose was unrelated to infant NAS severity. CONCLUSIONS: Conclusions: There were evident subclinical fetal neurophysiological responses at times of peak maternal buprenorphine/naloxone levels in later gestation, similar to those previously described for buprenorphine only. Further studies evaluating the effects of these changes in fetal neurobehaviors on the longer-term infant development are needed.

Buprenorphine-Naloxone Maintenance and Lactation.

BACKGROUND: Breastfeeding among lactating people with opioid use disorder taking buprenorphine monotherapy is generally accepted, as low concentrations of buprenorphine and metabolites in human milk have been well-established. The use of buprenorphine-naloxone for pregnant and lactating people with opioid use disorder is expanding and there is no information available regarding the concentrations of naloxone and their metabolites in human milk to recommend the use of this combination medication during lactation. RESEARCH AIMS: To determine the concentrations of buprenorphine and naloxone and their primary metabolites in human milk, maternal plasma, and infant plasma, among lactating buprenorphine-naloxone maintained people and their infants. METHODS: Four lactating buprenorphine-naloxone maintained people provided plasma and human milk samples on Days 2, 3, 4, 14, and 30 postpartum. Infant plasma was obtained on Day 14. RESULTS: Concentrations of buprenorphine, norbuprenorphine and their glucuronide metabolites were present in maternal plasma and human milk at low concentrations, consistent with previous research in lactating buprenorphine monotherapy participants. Naloxone was not detected, or was detected at concentrations below the limit of quantification, in maternal plasma and in all except one human milk sample at Day 30. Naloxone was not detected or detected at concentrations below the limit of quantification in all infant plasma samples. CONCLUSION: Results support the use of buprenorphine-naloxone by lactating people who meet appropriate criteria for breastfeeding.

Comparing Virtual and In-Person Implementation of a School-Based Sexual Health Promotion Program in High Schools with Large Latino Populations.

Many sexual health programs transitioned to virtual implementation during the COVID-19 pandemic. Despite its devastation, the pandemic provided an opportunity to learn about virtual compared to in-person implementation of a sexual health promotion program-El Camino. This study assessed differences in program attendance, engagement, quality, and student ratings for virtual versus in-person implementation of El Camino as part of a rigorous evaluation in high schools with high Latino populations in Maryland. Drawing on positive youth development practices, El Camino helps participants identify personal goals and learn about sexual reproductive health and healthy relationships. This mixed-methods study incorporates data from performance measures, baseline and post-intervention participant surveys, observations, monthly implementation reports, and debriefs with facilitators to describe and compare virtual and in-person program implementation. At baseline, participants were an average of 16.2 years old; between 8 and 12th grade; 61% female; 79% Hispanic, Latino, or of Spanish origin; and 54% spoke mostly Spanish at home. Recruitment and retention of students outside of school classes were challenging for both forms of implementation. However, attendance was higher during in-person implementation and in schools where the organization implementing El Camino had a strong presence before the pandemic. Findings indicate high fidelity, excellent quality ratings, and positive student perceptions of the program and facilitators in both the virtual and in-person cohorts, which suggest that both forms of implementation were comparable and furthermore highlight the strength of the virtual adaptation of the El Camino program.

Treatment for substance use disorders in pregnant women: Motivators and barriers.

BACKGROUND: Pregnancy is a unique opportunity to provide broad and necessary medical care for women- including treatment for Substance Use Disorders (SUD). The standard of care for SUD in pregnant women is treatment at a comprehensive care facility. There is little existing qualitative research exploring what brings pregnant women with SUD to treatment and what barriers to treatment exist for this population. This study explored women's self-reported reasons for pursuing treatment or hesitating to do so. METHODS: This qualitative study used interviews to explore common factors that motivate pregnant women with SUD to seek comprehensive care during pregnancy and common hesitations/ barriers to treatment. The study population included 20 women in treatment at a comprehensive care facility for pregnant and parenting women at Johns Hopkins. Participants volunteered to do interviews which were recorded and transcribed for analysis. RESULTS: Interviews revealed several major themes in motivators to seek treatment: readiness to stop using, concern for the baby's health, concern about custody of the baby or other children, wanting to escape violent environments or homelessness, and seeking structure. Barriers to treatment included fear of loss of custody, not wanting to be away from children/partner, concern about stigma or privacy, and lack of childcare and transportation. CONCLUSIONS: This study revealed common motivators to seek treatment and barriers to treatment for pregnant women with SUD. These themes may help direct future studies and guide efforts to increase access to crucial care in this vulnerable population.

Maternal buprenorphine treatment during pregnancy and maternal physiology.

BACKGROUND: Buprenorphine, used for opioid use disorder (OUD) treatment during pregnancy, provides unknown effects on maternal physiological activity. The primary aim of this report is to document acute effects of buprenorphine administration on indicators of maternal autonomic functioning. Effects of maternal buprenorphine dose and other substance exposures on maternal measures were examined, as were neonatal abstinence syndrome (NAS) outcomes. METHODS: Forty-nine pregnant, buprenorphine-maintained women yielded maternal physiologic information (heart rate and variability, electrodermal activity, and respiratory rate) at 24, 28, 32 and 36 weeks gestation. Monitoring at trough and peak maternal medication levels was implemented to ascertain acute physiologic effects of buprenorphine administration. RESULTS: Buprenorphine administration accelerated maternal heart rate and reduced variability at two gestational ages (24 and 36 weeks) and suppressed sympathetic (electrodermal) activation at 24, 28 and 32 weeks at times of peak maternal medication levels. Maternal autonomic parameters were unrelated to polysubstance exposure with the exception of cigarette smoking. Heavier smoking dampened maternal heart rate variability across gestation and potentiated reactivity to buprenorphine at 24 and 36 weeks. Heavier smoking was also associated with reduced electrodermal activity at 36 weeks. Buprenorphine dose was unrelated to observed effects. Larger degree of maternal heart rate reactivity to buprenorphine administration was related to more severe NAS expression. CONCLUSIONS: These findings detail the maternal autonomic response to buprenorphine administration but also illustrate the significant effect of concurrent cigarette use on maternal autonomic regulation. This suggests the importance of smoking-reduction strategies in the comprehensive, medication-assisted treatment of women with OUD.

Prenatal buprenorphine exposure and neonatal neurobehavioral functioning.

AIMS: Assessments of effects of prenatal opioid exposure on the neonate have consisted principally of evaluations of neonatal abstinence syndrome (NAS) to determine the need for pharmacotherapy. The purpose of this study was to comprehensively evaluate the effects of gestational maternal buprenorphine maintenance on newborn neurobehavioral functioning. STUDY DESIGN: Maternal substance use history and psychosocial demographics that can contribute to the neurobehavioral functioning of the infant were explored. Infants were assessed using the NICU Network Neurobehavioral Scale (NNNS) to measure their neurologic and behavioral functioning and signs of stress/abstinence on days 3, 14 and 30 of life. SUBJECTS: Participants were 41 pregnant buprenorphine-maintained women and their infants. RESULTS: Maternal buprenorphine dose at delivery was negatively correlated with infant quality of movement and self-regulation, and positively correlated with the central nervous system parameters of stress/abstinence at day 3 of life. As maternal buprenorphine dose increased, the mean morphine dose that the infant required for NAS treatment significantly increased. No differences were found when comparing the NNNS domain scores between infants who required pharmacotherapy for NAS versus those who did not at day 3 of life. CONCLUSIONS: Buprenorphine exposure during pregnancy can alter neonatal neurobehavioral and physiological responses to stimuli. A systematic evaluation of the newborn's functional domains above NAS assessment alone is crucial to address the challenges created by neurobehavioral dysregulation associated with substance exposure, improve caregiver/infant interaction and developmental trajectory. Comprehensive pre/postnatal treatment of buprenorphine-maintained mothers can lead to healthier outcomes for the dyad.

Maternal buprenorphine treatment and infant outcome.

BACKGROUND AND OBJECTIVES: Maternal buprenorphine maintenance predisposes the infant to exhibit neonatal abstinence syndrome (NAS), but there is insufficient published information regarding the nature of NAS and factors that contribute to its severity in buprenorphine-exposed infants. METHODS: The present study evaluated forty-one infants of buprenorphine-maintained women in comprehensive substance use disorder treatment who participated in an open-label study examining the effects of maternal buprenorphine maintenance on infant outcomes. Modifiers of the infant outcomes, including maternal treatment and substance use disorder parameters, were also evaluated. RESULTS: Fifty-nine percent of offspring exhibited NAS that required pharmacologic management. Both maternal buprenorphine dose as well as prenatal polysubstance exposure to illicit substance use/licit substance misuse were independently associated with NAS expression. Polysubstance exposure was associated with more severe NAS expression after controlling for the effects of buprenorphine dose. Other exposures, including cigarette smoking and SRI use, were not related to outcomes. Maternal buprenorphine dose was positively associated with lower birth weight and length. CONCLUSIONS: Polysubstance exposure was the most potent predictor of NAS severity in this sample of buprenorphine-exposed neonates. This finding suggests the need for interventions that reduce maternal polysubstance use during medication assisted treatment for opioid use disorder, and highlights the necessity of a comprehensive approach, beyond buprenorphine treatment alone, for the optimal care for pregnant women with opioid use disorders.

Maternal buprenorphine treatment and fetal neurobehavioral development.

BACKGROUND: Gestational opioid use/misuse is escalating in the United States; however, little is understood about the fetal effects of medications used to treat maternal opioid use disorders. OBJECTIVE: The purpose of this study was to determine the effect of maternal buprenorphine administration on longitudinal fetal neurobehavioral development. STUDY DESIGN: Forty-nine buprenorphine-maintained women who attended a substance use disorder treatment facility with generally uncomplicated pregnancies underwent fetal monitoring for 60 minutes at times of trough and peak maternal buprenorphine levels. Data were collected at 24, 28, 32, and 36 weeks gestation. Fetal neurobehavioral indicators (ie, heart rate, motor activity, and their integration [fetal movement-fetal heart rate coupling]) were collected via an actocardiograph, digitized and quantified. Longitudinal data analysis relied on hierarchic linear modeling. RESULTS: Fetal heart rate, heart rate variability, and heart rate accelerations were significantly reduced at peak vs trough maternal buprenorphine levels. Effects were significant either by or after 28 weeks gestation and tended to intensify with advancing gestation. Fetal motor activity and fetal movement-fetal heart rate coupling were depressed from peak to trough at 36 weeks gestation. Polysubstance exposure did not significantly affect fetal neurobehavioral parameters, with the exception that fetuses of heavier smokers moved significantly less than those of lighter smokers at 36 weeks gestation. By the end of gestation, higher maternal buprenorphine dose was related to depression of baseline fetal cardiac measures at trough. CONCLUSION: Maternal buprenorphine administration has acute suppressive effects on fetal heart rate and movement, and the magnitude of these effects increases as gestation progresses. Higher dose (≥13 mg) appears to exert greater depressive effects on measures of fetal heart rate and variability. These findings should be balanced against comparisons to gestational methadone effects, relatively good outcomes of buprenorphine-exposed infants, and recognition of the benefits of medication-assisted treatment for pregnant women with opioid use disorders in optimizing pregnancy outcomes.

Maternal Buprenorphine Maintenance and Lactation.

BACKGROUND: In addition to the well-known benefits of human milk and breastfeeding for the mother and infant, breastfeeding may mitigate neonatal abstinence syndrome severity in prenatally opioid-exposed infants. However, lack of conclusive data regarding the extent of the presence of buprenorphine and active metabolites in human milk makes the recommendation of breastfeeding for buprenorphine-maintained women difficult for many providers. OBJECTIVE: This study seeks to determine the concentrations of buprenorphine and its active metabolites (norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide) in human milk, maternal plasma, and infant plasma of buprenorphine-maintained women and their infants. METHODS: Up to 10 buprenorphine-maintained women provided paired breast milk and plasma samples at 2, 3, 4, 14, and 30 days postdelivery, and 9 infants provided plasma samples on day 14 of life. All samples were analyzed via liquid chromatography tandem mass spectrometry to determine concentrations of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide by a fully validated method. RESULTS: Concentrations of buprenorphine and metabolites are low in human milk and maternal plasma. Breastfed infant plasma concentrations of buprenorphine were low or undetectable and metabolite concentrations undetectable at 14 days of infant age. There were significant correlations between maternal buprenorphine dose and maternal plasma and human milk buprenorphine concentrations. CONCLUSION: These data find low concentrations of buprenorphine and metabolites in human milk and lend support to the recommendation for lactation among stable buprenorphine-maintained women. However, the correlation between maternal dose and maternal plasma and human milk buprenorphine concentrations bears further study.