Outcomes in Subsequent Pregnancies of Individuals With Opioid Use Disorder Treated in Multidisciplinary Clinic in Prior Pregnancy.

BACKGROUND: Untreated opioid misuse in pregnancy is associated with adverse outcomes. Limited information is available on maternal and perinatal outcomes in subsequent pregnancies for individuals initiated on medication for opioid use disorder (MOUD) in a prior pregnancy. OBJECTIVE: Evaluate maternal and neonatal outcomes in subsequent pregnancies for individuals initiated on MOUD in prior pregnancy. METHODS: Historical cohort study including individuals with opioid use disorder with ≥2 pregnancies between 2013 and 2020, received care in our colocated multidisciplinary clinic for >1 pregnancy, and delivered at our institution. Primary outcome was rate of preconception MOUD. Secondary outcomes included rate of neonatal opioid withdrawal syndrome requiring pharmacologic treatment and length of hospital stay. RESULTS: Forty-two individuals with opioid use disorder in their index pregnancies (n = 42) and 46 subsequent pregnancies were identified. Individuals were more likely to receive long-acting reversible contraception in subsequent pregnancies (35% vs 14%, P = 0.04). No differences in tobacco use, gestational age at initiation of prenatal care or delivery was noted. Individuals in their subsequent pregnancies were 6 times more likely to be on MOUD preconception (78% vs 36%; OR, 6.48; [95% CI, 2.52-16.64]) and 67% less likely to have positive illicit urine drug screen upon initiation of care (36% vs 64%; OR, 0.33; 95% [CI, 0.14-0.78]). Neonates had similar rates of neonatal abstinence withdrawal syndrome requiring pharmacological treatment, positive illicit toxicology results, and neonatal length of stay. CONCLUSIONS: Participation in multidisciplinary obstetric and opioid use disorder program increases rate of MOUD in subsequent pregnancy with decrease in illicit drug use.

Opioids and the developing brain: time to rethink perinatal care for infants of opioid-dependent mothers.

Illicit use of opioids is a global health crisis with major implications for women and children. Strategies for managing opioid use disorder (OUD) in pregnancy have been tested over the past 40 years, but studies have focused on maternal and pregnancy outcomes, with less attention given to long-term follow-up of exposed children. Here, we provide a narrative review of recent advances in the assessment and management of neonatal opioid withdrawal syndrome (NOWS), and we summarise evidence from multiple domains-neuroimaging, electrophysiology, visual development and function, neurodevelopment, behaviour, cognition and education-which suggests that prenatal opioid exposure modifies child development. Further studies are required to determine the optimal management of pregnant women with OUD and babies with NOWS. We identify knowledge gaps and suggest that future study designs should evaluate childhood outcomes, including infant brain development and long-term neurocognitive and visual function.

Clinical care of neonates undergoing opioid withdrawal in the immediate postpartum period.

As the opioid epidemic escalates in westernized countries around the world, chronic opioid use during pregnancy has become a growing public health issue. There are increasing concerns that chronic maternal opioid use might adversely affect the developing fetal brain. Furthermore, the sudden discontinuation of the trans-placental opioid supply at birth puts newborns at acute risk for neonatal opioid withdrawal syndrome (NOWS). NOWS is a multi-system disorder that has been identified in approximately 50-80% of neonates exposed to opioids due to chronic maternal use. Clinically, NOWS affects the central and autonomic nervous systems as well as the gastrointestinal and respiratory tracts. The clinical features of NOWS include hyperirritability, high-pitched crying, restlessness, tremors, poor sleep, agitation, seizures, sweating, fever, poor feeding, regurgitation, diarrhea, and tachypnea. NOWS is currently diagnosed using a clinical scoring tool followed by toxicological confirmation of the presence of opioids in meconium or tissue specimens. The first-line treatments for NOWS are non-pharmacologic comfort measures. If these measures fail, neonates may be treated with opioids and/or sedatives. Since the severity of NOWS can be highly variable, it is quite difficult to predict which opioid-exposed neonates will require pharmacotherapy and prolonged hospitalization. Factors associated with maternal polysubstance use, including the use of illicit substances and tobacco, have been associated with the increased severity and duration of NOWS. Since neonates with NOWS are at increased risk for long-term adverse neurodevelopmental outcomes, ongoing monitoring beyond the neonatal period is essential.

Neonatal Opioid Withdrawal Syndrome.

The opioid crisis has grown to affect pregnant women and infants across the United States, as evidenced by rising rates of opioid use disorder among pregnant women and neonatal opioid withdrawal syndrome among infants. Across the country, pregnant women lack access to evidence-based therapies, including medications for opioid use disorder, and infants with opioid exposure frequently receive variable care. In addition, public systems, such as child welfare and early intervention, are increasingly stretched by increasing numbers of children affected by the crisis. Systematic, enduring, coordinated, and holistic approaches are needed to improve care for the mother-infant dyad. In this statement, we provide an overview of the effect of the opioid crisis on the mother-infant dyad and provide recommendations for management of the infant with opioid exposure, including clinical presentation, assessment, treatment, and discharge.

Comparison of buprenorphine and methadone in the management of maternal opioid use disorder in full term pregnancies.

Objectives To compare pregnancy outcomes with medication assisted treatment using. methadone or buprenorphine in term mothers with opioid use disorder. Methods A cohort of women receiving medication assisted treatment with either methadone or buprenorphine were identified from delivery records over a 10-year period. Women were excluded with delivery <37 weeks, multiple gestations, or a known anomalous fetus. Maternal demographics, medications, mode of delivery, birthweight, newborn length of stay, and neonatal abstinence syndrome were extracted. The study was IRB approved and a p-value of <0.05 was significant. Results There were 260 women, 140 (53.8%) with methadone use and 120 (46.2%) with buprenorphine use. Groups were similar for maternal age, race, parity, homeless rate, tobacco use, mode of delivery and incidence of neonatal abstinence syndrome. The methadone group had a lower mean newborn birthweight (2874±459 g) and a greater incidence of low birth weight (11.4%) than the buprenorphine group (3282±452 g; p<0.001 and 2.5%; p=0.006). The incidence of neonatal abstinence syndrome was similar between groups (97% methadone vs. 92.5% buprenorphine; p=0.08). The methadone group had a longer newborn length of stay (11.4+7.4 days) and more newborn treatment with morphine (44.6%) than the buprenorphine group (8.2+4.4 days; p<0.001 and 24.2%; p<0.001). Maternal methadone use was an independent predictor for a newborn length of hospital stay >7 days (OR 3.61; 95% confidence interval 1.32-9.86; p=0.01). Conclusions Medication assisted treatment favors buprenorphine use when compared to. methadone with an increased birthweight, reduced need for newborn treatment, and a shorter newborn length of stay in term infants.

Maternal hair cortisol levels as a novel predictor of neonatal abstinence syndrome severity: A pilot feasibility study.

Neonatal abstinence syndrome (NAS) after in-utero opioid exposure remains a poorly understood condition with multiple factors contributing to severity. Exposure to maternal stress may be one contributing factor. Hair cortisol measurement represents a novel technique for assessing prenatal stress. In this pilot study, the association between maternal hair cortisol levels and NAS severity was examined in 70 postpartum women with opioid use disorder within 72 hr of delivery. Infants were monitored for NAS and treated according to institutional protocol. Forty-four (63%) of the infants were pharmacologically treated for NAS, with a mean length of hospital stay (LOS) for all infants of 14.2 (SD 9.0) days. The mean cortisol level in the mothers was 131.8 pg/mg (SD 124.7). In bivariate analysis, higher maternal hair cortisol levels were associated with shorter infant LOS (R = -.26, p = .03) and fewer infant opioid treatment days (R = -.28, p = .02). Results were no longer statistically significant in regression models after adjusting for maternal opioid and smoking. In conclusion, we demonstrated the feasibility of hair cortisol assaying within the first few days after delivery in mothers with opioid use disorder as a novel marker for NAS. The findings suggest that maternal stress may impact the severity of infant opioid withdrawal.

Research and policy priorities for addressing prenatal exposure to opioids in Alaska.

The current opioid crisis in Alaska and the USA will negatively affect the health and wellbeing of future generations. The increasing number of infants born with neonatal opioid withdrawal syndrome (NOWS) has had a profound impact on families, health care providers and the child welfare system. This manuscript summarises the main themes of a Symposium held in Anchorage, Alaska with health care providers, researchers, elders and public health officials that focused on identifying emerging challenges, trends and potential solutions to address the increasing number of infants and children affected by maternal opioid use. Five areas of importance for research and policy development that would direct improvement in the care of infants with NOWS in Alaska are outlined with the goal of supporting a research agenda on opioid misuse and child health across the circumpolar north. Abbreviations: NOWS - neonatal opioid withdrawal syndrome; NAS - neonatal abstinence syndrome; MAT - medication-assisted treatment; NICU - neonatal intensive care unit; OATs - opioid agonist treatments; OCS - office of children's services; ANTHC - Alaska Native Tribal Health Consortium; OUD - opioid use disorder; SBIRT - screening, brief intervention and referral to treatment; ISPCTN - IDeA States Pediatric Clinical Trials Network; NIH - National Institutes of Health; ANMC - Alaska Native Medical Center; DHSS - Department of Health and Social Services; AAPP - All Alaska Pediatric Partnership.

Obstetric management of women with opioid use disorder.

Pregnancy presents a window of opportunity for effecting positive change in the lives of women with opioid use disorder (OUD). Care should be empathetic and nonjudgmental with a focus on counseling for initiation and maintenance of beneficial health behaviors as well as development of a strong patient-provider relationship.1 These include adherence to treatment of OUD through pharmacotherapy and behavioral counseling, smoking cessation, healthy nutrition, treatment of coexisting medical and psychosocial conditions, as well as preparation for the postpartum period through breastfeeding education and antenatal discussion of contraception. Women will also benefit from anticipatory guidance with regard to neonatal abstinence syndrome (see Chapter 7). This may include a consultation with pediatric or neonatal providers who will be caring for their infants. In the absence of other obstetric indications, minimal additional fetal assessment outside that of standard prenatal care is recommended for OUD.

Antenatal methadone vs buprenorphine exposure and length of hospital stay in infants admitted to the intensive care unit with neonatal abstinence syndrome.

OBJECTIVE: Antenatal exposure to methadone or buprenorphine often causes neonatal abstinence syndrome (NAS) in newborns. However, comparative effects on affected infants' hospital courses are inconclusive. We sought to estimate the relationship of antenatal exposure with methadone or buprenorphine and infants' length of stay among hospitalized infants with NAS. STUDY DESIGN: This was a retrospective cohort study of hospitalized infants with NAS with either maternal exposure. Eligible infants were singleton infants born ⩾36 weeks' gestation and diagnosed with NAS<7 days of age between 2011 and 2014 in the Pediatrix Clinical Data Warehouse. Infant with congenital anomalies and those of multiple gestation were excluded. RESULTS: Of 3364 eligible infants, 2202 (65%) were exposed to methadone and 1162 (34%) to buprenorphine. Infants exposed to buprenorphine had a lower rate of pharmacologic treatment for NAS (88 vs 91%, P<0.001). Median length of hospital stay was shorter among infants exposed to buprenorphine (21 days (inter-quartile range; 13-31) vs methadone (24 days (15-38), P<0.0001)). On multivariable Cox proportional hazard analyses, buprenorphine was associated with a shorter length of stay (hazard ratio (HR)=1.47 (95% confidence interval (CI): 1.32-1.62, P<0.001) after controlling for maternal age, parity, race or ethnicity, prenatal care, smoking status, use of antidepressants, use of benzodiazepines, and infant gestational age, small for gestational age status, cesarean delivery, sex, out born status, type of pharmacotherapy, breast milk use, year and center. We observed similar results in model using infants matched 1:1 with propensity scores for antenatal medication exposure (HR 1.39 for buprenorphine, CI 1.32-1.62, P<0.001). CONCLUSION: Among infants born ⩾36 weeks' gestation with NAS, antenatal buprenorphine exposure was associated with a decreased length of stay relative to antenatal methadone exposure.

Tailoring a NICU-Based Tobacco Treatment Program for Mothers Who Are Dependent on Opioids.

OBJECTIVE: To collect formative information to design a tailored tobacco treatment intervention for women with newborns treated or evaluated for neonatal abstinence syndrome and to explore current tobacco use behaviors and facilitators and barriers to smoking cessation. DESIGN: Qualitative descriptive study. SETTING: An academic medical center in the southern United States. PARTICIPANTS: Mothers (N = 11) of newborns who were treated or evaluated for neonatal abstinence syndrome at birth within the preceding 3 months. Women recruited were older than 18 years and reported opioid dependence and smoking during pregnancy. METHODS: Participants took part in semistructured individual interviews that lasted approximately 1 hour. Interviews were professionally transcribed and analyzed in MAXQDA using content analysis. RESULTS: Five themes emerged from the data: Strategizing to Reduce Risk, Desire to Quit Smoking in the Future, Holding on to Smoking While Working Through Recovery, Feeling Judged by Nurses, and Feeling Supported and Empowered by Nurses. Participants reported that they to reduce risk to their newborns by avoiding second- and thirdhand smoke exposure. Participants wanted to stop smoking but reported many barriers, including multiple life stressors compounded by their newborns' extended stays in the hospital. However, most participants described overall positive experiences and the support of health care providers. CONCLUSION: Holistic tobacco treatment programs that incorporate stress relief and social support and are led by trusted health care providers have the potential to be effective to reduce smoking in new mothers with histories of opioid dependence disorders and smoking and whose newborns are in the NICU.

Neonatal pain management.

Pain management in the neonatal ICU remains challenging for many clinicians and in many complex care circumstances. The authors review general pain management principles and address the use of pain scales, non-pharmacologic management, and various agents that may be useful in general neonatal practice, procedurally, or at the end of life. Chronic pain and neonatal abstinence are also noted.

How long should infants at risk of drug withdrawal be monitored after birth?

AIM: Neonatal abstinence syndrome (NAS) is an increasingly common disorder diagnosed in infants exposed to various drugs, causing immense financial and social burden. Recommendations from various bodies are for babies to be monitored for 4 to 7 days following birth so that prompt treatment can commence should symptoms develop. We aimed to determine the best post-natal observation period in babies at risk of NAS. METHODS: A retrospective review was undertaken of infants ≥35 weeks' gestation who received treatment for NAS in the period 2001-2010. During this time, the standard post-natal observation period was a minimum of 7 days. Data including drug exposure, day of admission and day of treatment were collected. RESULTS: Two hundred and ten babies were included. Drug exposure was predominantly to opiates (99%); however, most infants (58%) were exposed to additional substances (benzodiazepines, cannabis or amphetamines). Ninety-five per cent of infants were admitted by day 5 of life. Of the babies treated by day 7, 98.5% had been admitted to the nursery by day 5. Infants with polydrug exposure were admitted significantly earlier; however, time to treatment was not significantly different to those exposed to opiate replacement therapy alone. CONCLUSIONS: In our hospital, babies treated for NAS often required admission before day 5. This has implications for hospital resource allocation, suggesting that routine post-natal observation for NAS could be shortened to 5 days. Further research is needed to help identify neonates who require more careful post-natal observation.

Management of neonatal abstinence syndrome from opioids.

Most infants at risk for neonatal abstinence syndrome have opioid plus another drug exposure; polypharmacy is the rule rather than the exception. Scales for evaluation of neonatal abstinence syndrome are primarily based for opioid withdrawal. A standard protocol to treat neonatal abstinence syndrome has not been developed. Institute nonpharmacologic strategies for all neonates at risk. The American Academy of Pediatrics recommends mechanism-directed therapy (treat opioid withdrawal with an opioid) as the first-line therapy. Second-line medications are currently under evaluation.

Predictors of neonatal outcomes amongst a methadone- and/or heroin-dependent population referred to a multidisciplinary Perinatal and Family Drug Health Service.

BACKGROUND AND AIMS: Although methadone maintenance therapy is the standard of care for opioid-dependent pregnant women, there exists controversy over the benefits and side effects of treatment to the neonate. Our aim was to document predictors of neonatal outcomes within an opioid-using population, with particular reference to methadone treatment in the context of continued heroin use. METHODS: Analysis was performed on a cohort of 183 opioid-using pregnant women seen by the Sydney South West Area Health Service between 2004 and 2007 and between 2009 and 2011. Neonatal outcomes were analysed according to maternal opioid use: methadone only, methadone and heroin, or heroin only. Logistic regression was used to examine independent predictors of neonatal outcomes. RESULTS: No difference in the frequency of low birth weight neonates or the rate of prematurity was found between the methadone-only, methadone-and-heroin and heroin-only groups (P = 0.30; P = 0.42). Methadone treatment was not found to increase the treatment requirement for neonatal abstinence syndrome compared with those using heroin only (P = 0.91). Women using methadone only were more likely to retain custody of their child at hospital discharge than women using methadone and heroin and heroin only (80.4, 59.0, 40.0%; P < 0.001). CONCLUSIONS: Methadone treatment was beneficial in predicting the discharge custody status of the neonate. Engagement with antenatal care was found to reduce the likelihood of preterm birth and to be independently associated with the neonate being discharged in the care of the mother. Women who continue to use heroin should not be denied methadone treatment for fear of worse neonatal outcomes.

A rooming-in program to mitigate the need to treat for opiate withdrawal in the newborn.

OBJECTIVE: The purpose of this study was to explore the effect of our rooming-in protocol on the need to treat withdrawal in the opiate-exposed newborn. METHODS: We reviewed the medical records of mother-infant dyads born between October 1, 2003, and December 31, 2006, who received care in our rooming-in program. Data on the type of drug used by the mother, maternal methadone dose at delivery, morphine treatment of the baby, and perinatal outcome were considered. RESULTS: We found a significant positive relationship between maternal methadone dose at delivery, "other opiate" use, and breastfeeding and the need to treat the neonate for withdrawal. We also found the maternal methadone dose at delivery to be related to the duration of pharmacological treatment of the neonate. CONCLUSION: Our findings suggest a role for our rooming-in program in mitigating the relationship between maternal methadone dosage and the need to treat opiate withdrawal in the newborn. Consideration of the role played by the mother-infant dyad model of care needs to be considered in future studies.

Substance use in pregnancy.

OBJECTIVE: To improve awareness and knowledge of problematic substance use in pregnancy and to provide evidence-based recommendations for the management of this challenging clinical issue for all health care providers. OPTIONS: This guideline reviews the use of screening tools, general approach to care, and recommendations for clinical management of problematic substance use in pregnancy. OUTCOMES: Evidence-based recommendations for screening and management of problematic substance use during pregnancy and lactation. EVIDENCE: Medline, PubMed, CINAHL, and The Cochrane Library were searched for articles published from 1950 using the following key words: substance-related disorders, mass screening, pregnancy complications, pregnancy, prenatal care, cocaine, cannabis, methadone, opioid, tobacco, nicotine, solvents, hallucinogens, and amphetamines. Results were initially restricted to systematic reviews and randomized control trials/controlled clinical trials. A subsequent search for observational studies was also conducted because there are few RCTs in this field of study. Articles were restricted to human studies published in English. Additional articles were located by hand searching through article reference lists. Searches were updated on a regular basis and incorporated in the guideline up to December 2009. Grey (unpublished) literature was also identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on the Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1). BENEFITS, HARMS, AND COSTS: This guideline is intended to increase the knowledge and comfort level of health care providers caring for pregnant women who have substance use disorders. Improved access to health care and assistance with appropriate addiction care leads to reduced health care costs and decreased maternal and neonatal morbidity and mortality. RECOMMENDATIONS: 1. All pregnant women and women of childbearing age should be screened periodically for alcohol, tobacco, and prescription and illicit drug use. (III-A) 2. When testing for substance use is clinically indicated, urine drug screening is the preferred method. (II-2A) Informed consent should be obtained from the woman before maternal drug toxicology testing is ordered. (III-B) 3. Policies and legal requirements with respect to drug testing of newborns may vary by jurisdiction, and caregivers should be familiar with the regulations in their region. (III-A) 4. Health care providers should employ a flexible approach to the care of women who have substance use problems, and they should encourage the use of all available community resources. (II-2B) 5. Women should be counselled about the risks of periconception, antepartum, and postpartum drug use. (III-B) 6. Smoking cessation counselling should be considered as a first-line intervention for pregnant smokers. (I-A) Nicotine replacement therapy and/or pharmacotherapy can be considered if counselling is not successful. (I-A) 7. Methadone maintenance treatment should be standard of care for opioid-dependent women during pregnancy. (II-IA) Other slow-release opioid preparations may be considered if methadone is not available. (II-2B) 8. Opioid detoxification should be reserved for selected women because of the high risk of relapse to opioids. (II-2B) 9. Opiate-dependent women should be informed that neonates exposed to heroin, prescription opioids, methadone, or buprenorphine during pregnancy are monitored closely for symptoms and signs of neonatal withdrawal (neonatal abstinence syndrome). (II-2B) Hospitals providing obstetric care should develop a protocol for assessment and management of neonates exposed to opiates during pregnancy. (III-B) 10. Antenatal planning for intrapartum and postpartum analgesia may be offered for all women in consultation with appropriate health care providers. (III-B) 11. The risks and benefits of breastfeeding should be weighed on an individual basis because methadone maintenance therapy is not a contraindication to breastfeeding. (II-3B).

Predicting length of treatment for neonatal abstinence syndrome in methadone-exposed neonates.

OBJECTIVE: The objective of the study was to identify maternal variables predicting length of treatment for neonatal abstinence syndrome (NAS). STUDY DESIGN: This was a retrospective cohort study of infants treated for NAS during 2000-2006 whose mothers were on methadone maintenance at delivery. Mixed-effects linear regression was used to examine the interaction of maternal and neonatal variables with length of treatment. RESULTS: Of 204 neonates born to methadone exposed mothers, the average dose at delivery was 127 mg daily (25-340 mg) with median length of treatment 32 days (1-122 days). Trimester of initial exposure (P = .33), methadone dose at delivery (P = .198), body mass index (P = .31), antidepressant use (P = .40), cigarette use (P = .76), race (P = .78), and maternal age (P = .84) did not predict length of treatment. In the multivariate analysis, gestational age at delivery and benzodiazepine use were significant predictors of length of treatment. CONCLUSION: Later gestational age and concomitant benzodiazepine use were associated with longer treatment.