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.

Reconceptualizing non-pharmacologic approaches to Neonatal Abstinence Syndrome (NAS) and Neonatal Opioid Withdrawal Syndrome (NOWS): A theoretical and evidence-based approach. Part II: The clinical application of nonpharmacologic care for NAS/NOWS.

There has been increasing emphasis on the importance of the development of self-regulatory capacities of the individual as the cornerstone of development. The caregivers' abilities to manage their own attention, emotions, physiology and behaviors influence the development of the child's self-regulatory and interactive capacities, and thereby their overall development. Newborns prenatally exposed to psychoactive substances and/or to other prenatal stressors such as maternal poor nutrition, increased maternal stress, trauma, difficult and/or impoverished environments, in tandem with genetic predispositions, can result in alterations to their neurodevelopment that predispose them to self-regulatory problems that can be expressed at any stage of life. The care of infants with Neonatal Abstinence Syndrome (NAS)/Neonatal Opioid Withdrawal Syndrome (NOWS) and their mother/caregiver is a window of opportunity to assess the regulatory and co-regulatory capacities of both, and to provide holistic interventions with the goal of empowering the mother/caregiver in their own self-knowledge/self-regulation capacities and their crucial role in promoting the healthy development of their children. Non-pharmacologic care for the infant with NAS/NOWS is the first line of treatment and of paramount importance. Yet, current approaches are based on a limited scope of infant functioning, and the scoring systems in current use do not result in individualized and specific non-pharmacologic care of the infant, which can result in excessive or insufficient medication and a lack of caregiver appreciation for the infant's strengths, difficulties and early development. The interventions described here are based on the infant's signs of dysregulation in four neurobehavioral subsystems that can be dysregulated by NAS/NOWS, the infant's adaptive or maladaptive responses to return to a regulated functioning, and the co-regulatory behaviors of the infant and the mother/caregiver. In Part I of this two-part series on re-conceptualizing non-pharmacologic care for NAS/NOWS we laid the foundation for a new treatment approach, one grounded in developmental theory and evidence-based observations of infant and interpersonal neurobiology. Here, in Part II, we outline actionable, individually tailored evaluations and approaches to non-pharmacologic NAS/NOWS treatment based on strategies to support the regulatory capacities and development of 4 key domains: 1) autonomic; 2) motor/tone; 3) sleep/awake state control; and 4) sensory modulation subsystems.

Reconceptualizing non-pharmacologic approaches to Neonatal Abstinence Syndrome (NAS) and Neonatal Opioid Withdrawal Syndrome (NOWS): A theoretical and evidence-based approach.

Discussions about non-pharmacologic interventions for Neonatal Abstinence Syndrome and Neonatal Opioid Withdrawal Syndrome (NAS/NOWS) have been minor compared with wider attention to pharmacologic treatments. Although historically under-recognized, non-pharmacologic interventions are of paramount importance for all substance-exposed infants and remain as a first line therapy for the care of infants affected by NAS. Here we examine the role of non-pharmacologic interventions for NAS/NOWS by incorporating theoretical perspectives from different disciplines that inform the importance of individualized assessment of the mother-caregiver/infant dyad and interventions that involve both individuals. NAS/NOWS is a complex, highly individualized constellation of signs/symptoms that vary widely in onset, duration, severity, expression, responses to treatment and influence on long-term outcomes. NAS/NOWS often occurs in infants with multiple prenatal/postnatal factors that can compromise neurobiological self-regulatory functioning. We propose to rethink some of the long-held assumptions, beliefs, and paradigms about non-pharmacologic care of the infant with NAS/NOWS, which is provided as non-specific or as "bundled" in current approaches. This paper is Part I of a two-part series on re-conceptualizing non-pharmacologic care for NAS/NOWS as individualized treatment of the dyad. Here, we set the foundation for a new treatment approach grounded in developmental theory and evidence-based observations of infant neurobiology and neurodevelopment. In Part II, we provide actionable, individually tailored evaluations and approaches to non-pharmacologic NAS/NOWS treatment based on measurable domains of infant neurobehavioral functioning.

Pregnancy-Associated Deaths from Homicide, Suicide, and Drug Overdose: Review of Research and the Intersection with Intimate Partner Violence.

The leading causes of pregnancy-associated deaths, as defined by the Centers for Disease Control and Prevention, are homicide, suicide, and drug overdose. Intimate partner violence during pregnancy has been shown to contribute to maternal mortality from pregnancy-associated deaths. In this article, we discuss these leading causes of pregnancy-associated deaths. We review the prevalence, demographic characteristics, and possible factors leading to each cause of death, as well as evidence-based methods of identification, prevention, and intervention. The review also will include data showing racial and ethnic inequities. In addition, we identify gaps and guiding questions for further research, as well as suggestions for immediate changes in practice and policy.

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.

The Effect of Sexual Abuse and Prenatal Substance Use on Successful Breastfeeding.

Barriers to breastfeeding in women with substance use disorders (SUDs) often exist. Neonatal abstinence syndrome-related feeding difficulties, maternal SUD-related maladaptive behaviors, and psychological comorbidities can adversely affect breastfeeding. A neglected barrier that frequently occurs in women with SUDs is a history of sexual abuse. It is important that nurses and providers understand each maternal and/or infant factor that can affect the breastfeeding course to assist effectively with lactation support for these frequently misunderstood dyads.

Síndrome de estrés postraumático en mujeres embarazadas abusadoras de drogas / Post-traumatic stress syndrome in pregnant women with drug addiction

Introducción: La exposición a eventos traumáticos es muy frecuente en mujeres con problemas de abuso de sustancias, pero no todas desarrollan síndrome de estrés postraumático (SEP). Pacientes con SEP tienen más problemas médicos, problemas interpersonales, usan drogas más fuertes y son más resistentes al tratamiento de adicción que pacientes sin este trastorno. Método: Exploración de la prevalencia de SEP en 87 mujeres embarazadas en tratamiento para adicción a drogas, que reportaron historia de violencia actual o durante la vida y aceptaron evaluación e intervenciones para mejorar aspectos afectados por el trauma, usando la Escala Diagnóstica de Estrés Postraumático (PDS), y de la sintomatología psicológica asociada, usando el Cuestionario de Síntomas-90 revisado (SCL-90R). Resultados: Más de la mitad (50,6%) de las pacientes llenaron criterios diagnósticos de SEP. Las mujeres con SEP presentaron puntuaciones significativamente más altas en todas las subescalas del SCL- 90R, el Índice de Severidad Global (1,58 vs. 0,89) y el Índice de Síntomas Positivos de Distrés (2,24 vs.1,78) que las mujeres sin SEP. Conclusión: Los resultados señalan la importancia de la evaluación de trauma y sus consecuencias en las mujeres embarazadas que reciben tratamiento para el abuso de sustancias y la necesidad de implementar intervenciones más efectivas para mujeres con problemas de adicción y SEP...

Introduction: Trauma exposure is very coomon among women with substance abuse problems, but not all develop post-traumatic stress syndrome (PTSD). Patients with PTSD have more medical problems, interpersonal issues, drug use and are more resistant to addiction treatment than patients without this disorder. Method: To study the prevalence of SEP in 87 pregnant women in treatment for drug addiction, who reported current or history of violence and accepted lifetime assessment and interventions to improve areas affected by the trauma, using the Posttraumatic Stress Diagnostic Scale (PDS), and associated psychological symptoms using the Symptom Checklist Questionnaire-90 Revised (SCL-90R). Results: Over half (50.6%) of patients fulfilled criteria for PTSD. The women with PTSD scored significantly higher on all subscales of the SCL-90R, the Global Severity Index (1.58 vs. 0.89) and the Positive Symptoms Distress Index (2.24 vs.1.78) than women without PTSD. Conclusion: Results highlight the importance of assessing trauma and its consequences in pregnant women receiving treatment for substance abuse and the need to implement more effective interventions for women with addiction problems and PTSD...

Prenatal methadone exposure and neonatal neurobehavioral functioning.

Opioid-exposed infants display a wide and variable range of dysregulated neurobehavioral functioning, but the regulatory difficulties experienced by these infants outside the defined clusters of neonatal abstinence syndrome (NAS) have not been well described and may have implications for the infant's developmental course. This study describes the neurobehavioral functioning of neonates prenatally exposed to methadone, using the NICU Network Neurobehavioral Scale (NNNS), and explores the relationships between maternal factors and infant functioning. The relationship between NNNS measures, NAS severity, and need for pharmacotherapy for NAS was also evaluated. Infants who required pharmacologic treatment for NAS showed more dysregulated behavior and signs of stress and abstinence as indicated by NNNS scores, but NNNS scores were not significantly correlated with maternal methadone dose. The determination of the range of the methadone-exposed infant's neurobehavioral repertoire could guide the optimal treatment of all such infants, particularly those requiring only nonpharmacologic care.

Methadone maintenance and long-term lactation.

Breastfeeding among methadone-maintained women is frequently challenged because of unclear guidelines regarding this practice. Previous research has confirmed that concentrations of methadone in breastmilk in the neonatal period are low. Currently unknown are the concentrations of methadone in breastmilk among women who breastfeed for longer periods of time. The purpose of this research is to examine concentrations of methadone in the plasma and breastmilk of women who breastfeed their infants beyond the neonatal period. Four methadone-maintained women provided blood and breastmilk samples up to 6 months postpartum. The concentrations of methadone in blood and breastmilk were low, contributing to the recommendation of breastfeeding for some methadone-maintained women.

Methadone maintenance and breastfeeding in the neonatal period.

OBJECTIVE: In a sample of methadone-maintained breastfeeding women and a matched group of formula-feeding women, this study evaluated concentrations of methadone in breast milk among breastfeeding women and concentrations of methadone in maternal and infant plasma in both groups. METHODS: Eight methadone-maintained (dose: 50-105 mg/day), lactating women provided blood and breast milk specimens on days 1, 2, 3, 4, 14, and 30 after delivery, at the times of trough and peak maternal methadone levels. Paired specimens of foremilk and hindmilk were obtained at each sampling time. Eight matched formula-feeding subjects provided blood samples on the same days. Infant blood samples for both groups were obtained on day 14. Urine toxicological screening between 36 weeks of gestation and 30 days after the birth confirmed that subjects were not using illicit substances in the perinatal period. RESULTS: Concentrations of methadone in breast milk were low (range: 21.0-462.0 ng/mL) and not related to maternal dose. There was a significant increase in methadone concentrations in breast milk over time for all 4 sampling times. Concentrations of methadone in maternal plasma were not different between groups and were unrelated to maternal dose. Concentrations of methadone in infant plasma were low (range: 2.2-8.1 ng/mL) in all samples. Infants in both groups underwent neurobehavioral assessments on days 3, 14, and 30; there were no significant effects of breastfeeding on neurobehavioral outcomes. Fewer infants in the breastfed group required pharmacotherapy for neonatal abstinence syndrome, but this was not a statistically significant finding. CONCLUSION: Results contribute to the recommendation of breastfeeding for methadone-maintained women.

Exposure to violence among substance-dependent pregnant women and their children.

This study examined the prevalence of exposure to violence among drug-dependent pregnant women attending a multidisciplinary perinatal substance abuse treatment program. Participants (N = 715) completed the Violence Exposure Questionnaire within 7 days after their admission to the program. Their rates of lifetime abuse ranged from 72.7% for physical abuse to 71.3% for emotional abuse to 44.5% for sexual abuse. Their rates of abuse remained high during their current pregnancy, ranging from 40.9% for emotional abuse to 20.0% for physical abuse to 7.1% for sexual abuse. Nearly one third of the women reported having physical fights with their current partner (lifetime), and 25% of these women reported that children were present during those physical fights. A total of 30% of the women perceived a need for counseling regarding exposure to violence for themselves and 15% perceived a need for counseling for their children. Study findings confirm previous reports of high rates of abuse and violence exposure among substance-abusing pregnant women and their strong need for counseling for psychosocial sequelae. This study affirmed the value of routine screening for violence exposure in this at-risk population as well as the need to train therapists in specific strategies for helping such women address this complex array of problems.

Parenting knowledge among substance abusing women in treatment.

The purpose of this study was to assess parenting knowledge and beliefs among drug abusing pregnant and recently postpartum women engaged in a comprehensive substance abuse treatment program. The effects of a parenting skills training program for this population were evaluated. A Parenting Skills Questionnaire was developed and administered to a sample of 73 pregnant and drug-dependent women during their first week of substance abuse treatment and again approximately 7 weeks later, following parenting skills training. The questionnaire was designed to assess whether group and individual parenting sessions changed the subjects' knowledge and beliefs in four parenting domains: newborn care, feeding practices, child development and drug abuse during pregnancy. Pre-intervention scores for all parenting domains were low. Post- vs. pre-intervention comparisons showed significant increases in all domain scores after individual and group parenting skills training. Preliminary results obtained from this clinic-based sample suggest that these substance abusing mothers lacked important parenting knowledge and that this knowledge improved after comprehensive substance abuse treatment that included parenting training.

Genetic Aspects of Alcohol Use and Alcoholism in Women.

The factors influencing alcohol use and alcoholism are not the same in women as in men. Genetic factors may contribute to these differences.