Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes: Executive Summary of a Joint Workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, American College of Obstetricians and Gynecologists, American Academy of Pediatrics, Society for Maternal-fetal Medicine, Centers for Disease Control and Prevention, and the March of Dimes Foundation
TL;DR: The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) hosted a workshop to address numerous knowledge gaps and to review the evidence for the screening and management of opioid use in pregnancy and neonatal abstinence syndrome as discussed by the authors.
About: This article is published in Obstetrics & Gynecology.The article was published on 2017-07-01 and is currently open access. It has received 165 citations till now. The article focuses on the topics: Complications of pregnancy & Pregnancy.
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TL;DR: Evidence pertaining to the optimal diagnosis and treatment strategies for neonatal abstinence syndrome is based on small or low-quality studies that focus on intermediate outcomes, such as need for pharmacologic treatment or length of hospital stay.
Abstract: Importance Neonatal abstinence syndrome, which occurs as a result of in utero opioid exposure, affects between 6.0 and 20 newborns per 1000 live US births. There is substantial variability in how neonatal abstinence syndrome is diagnosed and managed. Objective To summarize key studies examining the diagnosis and management (both pharmacologic and nonpharmacologic) of neonatal abstinence syndrome published during the past 10 years. Evidence Review PubMed, Web of Science, and CINAHL were searched for articles published between July 1, 2007, and December 31, 2017. Abstracts were screened and included in the review if they pertained to neonatal abstinence syndrome diagnosis or management and were judged by the authors to be clinical trials, cohort studies, or case series. Findings A total of 53 articles were included in the review, including 9 randomized clinical trials, 35 cohort studies, 1 cross-sectional study, and 8 case series—representing a total of 11 905 unique opioid-exposed mother-infant dyads. Thirteen studies were identified that evaluated established or novel neonatal abstinence syndrome assessment methods, such as brief neonatal abstinence syndrome assessment scales or novel objective physiologic measures to predict withdrawal. None of the new techniques that measure infant physiologic parameters are routinely used in clinical practice. The most substantial number of studies of neonatal abstinence syndrome management pertain to nonpharmacologic care—specifically, interventions that promote breastfeeding or encourage parents to room-in with their newborns. Although these nonpharmacologic interventions appear to decrease the need for pharmacologic treatment and result in shorter hospitalizations, the interventions are heterogeneous and there are no high-quality clinical trials to support them. Regarding pharmacologic interventions, only 5 randomized clinical trials with prespecified sample size calculations (4 infant, 1 maternal treatment) have been published. Each of these trials was small (from 26 to 131 participants) and tested different therapies, limiting the extent to which results can be aggregated. There is insufficient evidence to support an association between any diagnostic or treatment approach and differential neurodevelopmental outcomes among infants with neonatal abstinence syndrome. Conclusions and Relevance Evidence pertaining to the optimal diagnosis and treatment strategies for neonatal abstinence syndrome is based on small or low-quality studies that focus on intermediate outcomes, such as need for pharmacologic treatment or length of hospital stay. Clinical trials are needed to evaluate health and neurodevelopmental outcomes associated with objective diagnostic approaches as well as pharmacologic and nonpharmacologic treatment modalities.
137 citations
University of Utah1, Yeshiva University2, Seton Hall University3, University of Mississippi4, Kaiser Permanente5, Columbia University6, Medical University of South Carolina7, University of North Carolina at Chapel Hill8, Johns Hopkins University9, Pennsylvania State University10, University of Minnesota11, Alfred I. duPont Hospital for Children12, Wayne State University13, Brown University14
TL;DR: The need for large studies with prospectively recruited participants and longitudinal designs, taking into account confounding factors such as socioeconomic status, institutional variations in care, and maternal use of other substances, to independently assess the full impact of NOWS is highlighted.
Abstract: Neonatal opioid withdrawal syndrome (NOWS) has risen in prevalence from 1.2 per 1000 births in 2000 to 5.8 per 1000 births in 2012. Symptoms in neonates may include high-pitched cry, tremors, feeding difficulty, hypertonia, watery stools, and breathing problems. However, little is known about the neurodevelopmental consequences of prenatal opioid exposure in infancy, early childhood, and middle childhood. Even less is known about the cognitive, behavioral, and academic outcomes of children who develop NOWS. We review the state of the literature on the neurodevelopmental consequences of prenatal opioid exposure with a particular focus on studies in which NOWS outcomes were examined. Aiming to reduce the incidence of prenatal opioid exposure in the near future, we highlight the need for large studies with prospectively recruited participants and longitudinal designs, taking into account confounding factors such as socioeconomic status, institutional variations in care, and maternal use of other substances, to independently assess the full impact of NOWS. As a more immediate solution, we provide an agenda for future research that leverages the National Institutes of Health Environmental Influences on Child Health Outcomes program to address many of the serious methodologic gaps in the literature, and we answer key questions regarding the short- and long-term neurodevelopmental health of children with prenatal opioid exposure.
96 citations
05 Jun 2019
TL;DR: Prenatal opioid exposure was associated with higher risks of adverse perinatal and postnatal physical health and neurodevelopmental outcomes, suggesting that efforts to mitigate the health consequences of the opioid epidemic require more intergenerational research.
Abstract: Importance The opioid epidemic increasingly affects pregnant women and developing fetuses, resulting in high rates of neonatal abstinence syndrome. However, longitudinal studies that prospectively observe newborns with neonatal abstinence syndrome or with maternal opioid use and examine their long-term physical and neurodevelopmental outcomes are lacking. Objective To examine prenatal risk factors associated with maternal opioid use during pregnancy and the short-term and long-term health consequences on their children. Design, Setting, and Participants This cohort study analyzed data from the Boston Birth Cohort, an urban, low-income, multiethnic cohort that enrolled mother-newborn pairs at birth at Boston Medical Center (Boston, Massachusetts) starting in 1998, and a subset of children were prospectively observed at Boston Medical Center pediatric primary care and subspecialty clinics from birth to age 21 years. Data analysis began in June 2018 and was completed in May 2019. Exposures In utero opioid exposure was defined as maternal self-reported opioid use and/or clinical diagnosis of neonatal abstinence syndrome. Main Outcomes and Measures Pregnancy outcomes, postnatal child physical health, and major neurodevelopmental disabilities, documented in maternal and child medical records. Results This study included 8509 Boston Birth Cohort mother-newborn pairs for prenatal and perinatal analyses. Of those, 3153 children continued to receive pediatric care at Boston Medical Center and were included in assessing postnatal outcomes. Overall, 454 of the 8509 children (5.3%) in the Boston Birth Cohort had in utero opioid exposure. At birth, opioid exposure was associated with higher risks of fetal growth restriction (odds ratio [OR], 1.87; 95% CI, 1.41-2.47) and preterm birth (OR, 1.49; 95% CI, 1.19-1.86). Opioid exposure was associated with increased risks of lack of expected physiological development (OR, 1.80; 95% CI, 1.17-2.79) and conduct disorder/emotional disturbance (OR, 2.13; 95% CI, 1.20-3.77) among preschool-aged children. In school-aged children, opioid exposure was associated with a higher risk of attention-deficit/hyperactivity disorder (OR, 2.55; 95% CI, 1.42-4.57). Conclusions and Relevance In this sample of urban, high-risk, low-income mother-child pairs, in utero opioid exposure was significantly associated with adverse short-term and long-term outcomes across developmental stages, including higher rates of physical and neurodevelopmental disorders in affected children. Efforts to prevent the opioid epidemic and mitigate its health consequences would benefit from more intergenerational research.
94 citations
TL;DR: An analysis of >7000 children in Tennessee revealed that children with a history of Neonatal abstinence syndrome were significantly more likely to have a subsequent educational disability.
Abstract: BACKGROUND: Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome that can occur after intrauterine opioid exposure Adverse neurobehavioral outcomes have been documented in infants with NAS; however, educational outcomes have not been thoroughly examined We analyzed Tennessee data to understand the need for special educational services among infants who are born with NAS METHODS: By using Tennessee Medicaid and birth certificate data, infants who were born in Tennessee between 2008 and 2011 with a history of NAS were matched (1:3) to infants who were born during the same period without a history of NAS Groups were matched on the basis of sex, race and/or ethnicity, age, birth region of residence, and Medicaid enrollment status Data were linked to Tennessee Department of Education special education data during early childhood (3–8 years of age) Conditional multivariable logistic regression was used to assess associations between NAS and selected special education outcomes RESULTS: A total of 1815 children with a history of NAS and 5441 children without NAS were assessed Children with NAS were significantly more likely to be referred for a disability evaluation (351 of 1815 [193%] vs 745 of 5441 [137%]; P CONCLUSIONS: Results of this novel analysis linking health and education data revealed that children with a history of NAS were significantly more likely to have a subsequent educational disability
79 citations
TL;DR: Children born to opioid-dependent mothers are at modest- to high-risk of adverse neurodevelopment at least to middle childhood, and future studies should identify specific clinical and social factors underlying these challenges to improve outcomes.
59 citations
References
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TL;DR: This guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.
Abstract: Importance Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose. Objective To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care. Process The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category. Evidence Synthesis Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (≥1 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects. Recommendations There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone. Conclusions and Relevance The guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.
3,935 citations
Journal Article•
TL;DR: Nicotine, psychotropic drugs, and silicone implants are 3 important topics reviewed in this statement that are important to protect nursing infants from untoward effects of maternal medication but also to allow effective pharmacologic treatment of breastfeeding mothers.
Abstract: The American Academy of Pediatrics places emphasis on increasing breastfeeding in the United States. A common reason for the cessation of breastfeeding is the use of medication by the nursing mother and advice by her physician to stop nursing. Such advice may not be warranted. This statement is intended to supply the pediatrician, obstetrician, and family physician with data, if known, concerning the excretion of drugs into human milk. Most drugs likely to be prescribed to the nursing mother should have no effect on milk supply or on infant well-being. This information is important not only to protect nursing infants from untoward effects of maternal medication but also to allow effective pharmacologic treatment of breastfeeding mothers. Nicotine, psychotropic drugs, and silicone implants are 3 important topics reviewed in this statement.
951 citations
Journal Article•
811 citations
TL;DR: Between 2000 and 2009, a substantial increase in the incidence of NAS and maternal opiate use in the United States was observed, as well as hospital charges related to NAS.
Abstract: Context Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome primarily caused by maternal opiate use. No national estimates are available for the incidence of maternal opiate use at the time of delivery or NAS. Objectives To determine the national incidence of NAS and antepartum maternal opiate use and to characterize trends in national health care expenditures associated with NAS between 2000 and 2009. Design, Setting, and Patients A retrospective, serial, cross-sectional analysis of a nationally representative sample of newborns with NAS. The Kids' Inpatient Database (KID) was used to identify newborns with NAS by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code. The Nationwide Inpatient Sample (NIS) was used to identify mothers using diagnosis related groups for vaginal and cesarean deliveries. Clinical conditions were identified using ICD-9-CM diagnosis codes. NAS and maternal opiate use were described as an annual frequency per 1000 hospital births. Missing hospital charges ( Main Outcome Measures Incidence of NAS and maternal opiate use, and related hospital charges. Results The separate years (2000, 2003, 2006, and 2009) of national discharge data included 2920 to 9674 unweighted discharges with NAS and 987 to 4563 unweighted discharges for mothers diagnosed with antepartum opiate use, within data sets including 784 191 to 1.1 million discharges for children (KID) and 816 554 to 879 910 discharges for all ages of delivering mothers (NIS). Between 2000 and 2009, the incidence of NAS among newborns increased from 1.20 (95% CI, 1.04-1.37) to 3.39 (95% CI, 3.12-3.67) per 1000 hospital births per year (P for trend Conclusion Between 2000 and 2009, a substantial increase in the incidence of NAS and maternal opiate use in the United States was observed, as well as hospital charges related to NAS.
810 citations
TL;DR: A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group showed that the former group required significantly less morphine, which is consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women.
Abstract: Background Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy. Methods We conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference. Results Treatment wa...
771 citations