|
1
|
Wouldes TA, Lester BM. Opioid, methamphetamine, and polysubstance use: perinatal outcomes for the mother and infant. Front Pediatr 2023; 11:1305508. [PMID: 38250592 PMCID: PMC10798256 DOI: 10.3389/fped.2023.1305508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Accepted: 11/20/2023] [Indexed: 01/23/2024] Open
Abstract
The escalation in opioid pain relief (OPR) medications, heroin and fentanyl, has led to an increased use during pregnancy and a public health crisis. Methamphetamine use in women of childbearing age has now eclipsed the use of cocaine and other stimulants globally. Recent reports have shown increases in methamphetamine are selective to opioid use, particularly in rural regions in the US. This report compares the extent of our knowledge of the perinatal outcomes of OPRs, heroin, fentanyl, two long-acting substances used in the treatment of opioid use disorders (buprenorphine and methadone), and methamphetamine. The methodological limitations of the current research are examined, and two important initiatives that will address these limitations are reviewed. Current knowledge of the perinatal effects of short-acting opioids, OPRs, heroin, and fentanyl, is scarce. Most of what we know about the perinatal effects of opioids comes from research on the long-acting opioid agonist drugs used in the treatment of OUDs, methadone and buprenorphine. Both have better perinatal outcomes for the mother and newborn than heroin, but the uptake of these opioid substitution programs is poor (<50%). Current research on perinatal outcomes of methamphetamine is limited to retrospective epidemiological studies, chart reviews, one study from a treatment center in Hawaii, and the US and NZ cross-cultural infant Development, Environment And Lifestyle IDEAL studies. Characteristics of pregnant individuals in both opioid and MA studies were associated with poor maternal health, higher rates of mental illness, trauma, and poverty. Infant outcomes that differed between opioid and MA exposure included variations in neurobehavior at birth which could complicate the diagnosis and treatment of neonatal opioid withdrawal (NOWs). Given the complexity of OUDs in pregnant individuals and the increasing co-use of these opioids with MA, large studies are needed. These studies need to address the many confounders to perinatal outcomes and employ neurodevelopmental markers at birth that can help predict long-term neurodevelopmental outcomes. Two US initiatives that can provide critical research and treatment answers to this public health crisis are the US Environmental influences on Child Health Outcomes (ECHO) program and the Medication for Opioid Use Disorder During Pregnancy Network (MAT-LINK).
Collapse
Affiliation(s)
- Trecia A. Wouldes
- Department of Psychological Medicine, The University of Auckland, Auckland, New Zealand
| | - Barry M. Lester
- Center for the Study of Children at Risk, Warren Alpert Medical School, Brown University, Providence, RI, United States
| |
Collapse
|
|
2
|
Turner S, Allen VM, Carson G, Graves L, Tanguay R, Green CR, Cook JL. Guideline No. 443b: Opioid Use Throughout Women's Lifespan: Opioid Use in Pregnancy and Breastfeeding. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2023; 45:102144. [PMID: 37977721 DOI: 10.1016/j.jogc.2023.05.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2023]
Abstract
OBJECTIVE To provide health care providers the best evidence on opioid use and women's health. Areas of focus include pregnancy and postpartum care. TARGET POPULATION The target population includes all women currently using or contemplating using opioids. OUTCOMES Open, evidence-informed dialogue about opioid use will improve patient care. BENEFITS, HARMS, AND COSTS Exploring opioid use through a trauma-informed approach provides the health care provider and patient with an opportunity to build a strong, collaborative, and therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of opioid use disorders. Opioid use should not be stigmatized, as stigma leads to poor "partnered care" (i.e., the partnership between the patient and care provider). Health care providers need to understand the effect opioids can have on pregnant women and support them to make knowledgeable decisions about their health. EVIDENCE A literature search was designed and carried out in PubMed and the Cochrane Library databases from August 2018 until March 2023 using following MeSH terms and keywords (and variants): opioids, opioid agonist therapy, illicit drugs, fertility, pregnancy, fetal development, neonatal abstinence syndrome, and breastfeeding. VALIDATION METHODS The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE All health care providers who care for pregnant and/or post-partum women and their newborns. TWEETABLE ABSTRACT Opioid use during pregnancy often co-occurs with mental health issues and is associated with adverse maternal, fetal, and neonatal outcomes; treatment of opioid use disorder with agonist therapy for pregnant women can be safe during pregnancy where the risks outnumber the benefits. SUMMARY STATEMENTS RECOMMENDATIONS.
Collapse
|
|
3
|
Turner S, Allen VM, Carson G, Graves L, Tanguay R, Green CR, Cook JL. Directive clinique n o 443b : Opioïdes aux différentes étapes de la vie des femmes : Grossesse et allaitement. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2023; 45:102146. [PMID: 37977719 DOI: 10.1016/j.jogc.2023.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2023]
Abstract
OBJECTIF Présenter aux professionnels de la santé les données probantes concernant l'utilisation des opioïdes et la santé des femmes. Les domaines d'intérêt sont la grossesse et les soins post-partum. POPULATION CIBLE Toutes les femmes qui utilisent des opioïdes. RéSULTATS: Un dialogue ouvert et éclairé sur l'utilisation des opioïdes améliorera les soins aux patientes. BéNéFICES, RISQUES ET COûTS: L'exploration de l'utilisation d'opioïdes par une approche tenant compte des traumatismes antérieurs donne au professionnel de la santé et à la patiente l'occasion de bâtir une alliance solide, collaborative et thérapeutique. Cette alliance permet aux femmes de faire des choix éclairés. Elle favorise le diagnostic et le traitement possible du trouble lié à l'utilisation d'opioïdes. L'utilisation ne doit pas être stigmatisée, puisque la stigmatisation affaiblit le partenariat (le partenariat entre patiente et professionnel de la santé). Les professionnels de la santé ceus-ci doivent comprendre l'effet potentiel des opioïdes sur la santé les femmes enceintes et les aider à prendre des décisions éclairées sur leur santé. DONNéES PROBANTES: Une recherche a été conçue puis effectuée dans les bases de données PubMed et Cochrane Library pour la période d'août 2018 à mars 2023 des termes MeSH et mots clés suivants (et variantes) : opioids, opioid agonist therapy, illicit drugs, fertility, pregnancy, fetal development, neonatal abstinence syndrome et breastfeeding. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Tous les professionnels de la santé qui prodiguent des soins aux femmes et aux nouveaux-nés. RéSUMé POUR TWITTER: La consommation d'opioïdes pendant la grossesse coïncide souvent avec des problèmes de santé mentale et est associée à des conséquences néfastes pour la mère, le fœtus et le nouveau-né ; le traitement des troubles liés à la consommation d'opioïdes par agonistes peut être sûr pendant la grossesse lorsque les risques sont plus nombreux que les avantages. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.
Collapse
|
|
4
|
Zyoud SH, Al-Jabi SW, Shahwan MJ, Jairoun AA. Global research production in neonatal abstinence syndrome: A bibliometric analysis. World J Clin Pediatr 2022; 11:307-320. [PMID: 35663005 PMCID: PMC9134155 DOI: 10.5409/wjcp.v11.i3.307] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/21/2021] [Accepted: 03/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recently, neonatal abstinence syndrome (NAS) emerged as a significant global concern with a dramatic increase in healthcare expenditures. The incidence of the NAS has increased notably in the past decade and emergence as a global public health problem. AIM To evaluate the development and trend of global NAS research from 1958 to 2019 by bibliometric analysis. METHODS Analyzed aspects included publication output per year, language, document types, journals, countries/territories, h-index, authors, and top research priorities. The VOSviewer was used to determine the top research priorities, and trends, and to present bibliometric networks concerning various dimensions, such as co-authorship, authors, and countries. RESULTS A total of 1738 articles were retrieved in the Scopus database from 1958 to 2019. It was found that the great majority of the total NAS documents (n = 1295) were original articles followed by reviews (n = 268) and letters (n = 48). The most productive countries in the NAS field were the United States (n = 833), Canada (n = 112), the United Kingdom (n = 111), and Germany (n = 77). Treatment and hospital outcomes in NAS, evidence-based nurse-driven interventions for the care of newborns with NAS, and a systematic reviews and network meta-analysis for therapeutic approaches of NAS were found in recent years (after 2010), compared with terms such as pathophysiology, mechanisms of NAS, and signs and symptoms in the early years. CONCLUSION Treatment and pediatric outcomes and the effectiveness of pharmacological treatment may be frontiers in the NAS field, and continued efforts from researchers are needed in those topics.
Collapse
Affiliation(s)
- Sa'ed H Zyoud
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Poison Control and Drug Information Center, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Clinical Research Centre, An-Najah National University Hospital, Nablus 44839, Palestine
| | - Samah W Al-Jabi
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
| | - Moyad Jamal Shahwan
- Clinical Sciences, Ajman University, Ajman 2758, United Arab Emirates
- Centre of Medical and Bio‑allied Health Sciences Research, Ajman University, Ajman 2758, United Arab Emirates
| | | |
Collapse
|
|
5
|
Zyoud SH, Al-Jabi SW, Shahwan MJ, Jairoun AA. Global research production in neonatal abstinence syndrome: A bibliometric analysis. World J Clin Pediatr 2022; 11:308-321. [DOI: 10.5409/wjcp.v11.i3.308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recently, neonatal abstinence syndrome (NAS) emerged as a significant global concern with a dramatic increase in healthcare expenditures. The incidence of the NAS has increased notably in the past decade and emergence as a global public health problem.
AIM To evaluate the development and trend of global NAS research from 1958 to 2019 by bibliometric analysis.
METHODS Analyzed aspects included publication output per year, language, document types, journals, countries/territories, h-index, authors, and top research priorities. The VOSviewer was used to determine the top research priorities, and trends, and to present bibliometric networks concerning various dimensions, such as co-authorship, authors, and countries.
RESULTS A total of 1738 articles were retrieved in the Scopus database from 1958 to 2019. It was found that the great majority of the total NAS documents (n = 1295) were original articles followed by reviews (n = 268) and letters (n = 48). The most productive countries in the NAS field were the United States (n = 833), Canada (n = 112), the United Kingdom (n = 111), and Germany (n = 77). Treatment and hospital outcomes in NAS, evidence-based nurse-driven interventions for the care of newborns with NAS, and a systematic reviews and network meta-analysis for therapeutic approaches of NAS were found in recent years (after 2010), compared with terms such as pathophysiology, mechanisms of NAS, and signs and symptoms in the early years.
CONCLUSION Treatment and pediatric outcomes and the effectiveness of pharmacological treatment may be frontiers in the NAS field, and continued efforts from researchers are needed in those topics.
Collapse
Affiliation(s)
- Sa'ed H Zyoud
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine,Poison Control and Drug Information Center, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine,Clinical Research Centre, An-Najah National University Hospital, Nablus 44839, Palestine
| | - Samah W Al-Jabi
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
| | - Moyad Jamal Shahwan
- Clinical Sciences, Ajman University, Ajman 2758, United Arab Emirates,Centre of Medical and Bio‑allied Health Sciences Research, Ajman University, Ajman 2758, United Arab Emirates
| | | |
Collapse
|
|
6
|
Kinsella M, Halliday LOE, Shaw M, Capel Y, Nelson SM, Kearns RJ. Buprenorphine Compared with Methadone in Pregnancy: A Systematic Review and Meta-Analysis. Subst Use Misuse 2022; 57:1400-1416. [PMID: 35758300 DOI: 10.1080/10826084.2022.2083174] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
INTRODUCTION Illicit opioid use in pregnancy is associated with adverse maternal, neonatal, and childhood outcomes. Opioid substitution is recommended, but whether methadone or buprenorphine is the optimal agent remains unclear. METHODS We searched EMBASE, PubMed, Web of Science, Scopus, Open Gray, CINAHL and the Cochrane Central Registry of Controlled Trials (CENTRAL) from inception to April 2020 for randomized controlled trials (RCTs) and cohort studies comparing methadone and buprenorphine treatment for opioid-using mothers. Included studies assessed maternal and or neonatal outcomes. We used random-effects meta-analyses to estimate summary measures for outcomes and report these separately for RCTs and cohort studies. RESULTS Of 408 abstracts screened, 20 papers were included (4 RCTs, 16 cohort, 223 and 7028 participants respectively). All RCTs (4/4) had a high risk of bias and median (IQR) Newcastle Ottawa Scale for cohort studies was 7.5 (6-9). In both RCTs and cohort studies, buprenorphine was associated with; greater offspring birth weight (weighted mean difference [WMD] 343 g (95% CI: 40-645 g) in RCT and 184 g (95% CI: 121-247 g) in cohort studies); body length at birth (WMD 2.28 cm (95% CI: 1.06-3.49 cm) in RCTs and 0.65 cm (95% CI: 0.31-0.98 cm) in cohort studies); and reduced risk of prematurity (risk ratio [RR] 0.41 (95% CI: 0.18-0.93) in RCTs and 0.63 [95% CI: 0.53-0.75] in cohort studies) when compared to methadone. All other clinical outcomes were comparable. CONCLUSIONS Compared to methadone, buprenorphine was consistently associated with improved birthweight and gestational age, however given potential biases, results should be interpreted with caution.
Collapse
Affiliation(s)
- Michael Kinsella
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
| | - Lucy O E Halliday
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
| | | | | | - Scott M Nelson
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
| | - Rachel J Kearns
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
| |
Collapse
|
|
7
|
Labella MH, Eiden RD, Tabachnick AR, Sellers T, Dozier M. Infant neurodevelopmental outcomes of prenatal opioid exposure and polysubstance use. Neurotoxicol Teratol 2021; 86:107000. [PMID: 34116198 PMCID: PMC8277730 DOI: 10.1016/j.ntt.2021.107000] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 04/19/2021] [Accepted: 06/01/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND Prenatal opioid exposure has been linked to adverse birth outcomes and delays in infant development. Existing literature is limited by a simple group-differences approach as well as inadequate controls for sociodemographic factors and polysubstance exposure co-occurring with prenatal opioid use. METHOD The current study assessed cumulative opioid exposure (duration of prescribed and illicit opioid use) as a predictor of infant birth outcomes and mother-reported developmental status at three and six months of age, controlling for polysubstance exposure. Participants were predominantly low-income pregnant and peripartum women, oversampled for mothers receiving medication-assisted treatment (MAT) for opioid use disorder. Prenatal opioid and non-opioid substance use were reported by mothers using a Timeline Follow-Back Interview completed during the third trimester and updated postnatally (infant age six months). RESULTS Developmental scores were in the normal range. However, total opioid exposure was positively related to premature birth and inversely related to mother-reported developmental status in specific domains. Associations with three-month fine motor skills and six-month communication skills were robust to controls for polysubstance exposure and sociodemographic covariates. CONCLUSIONS Results suggest unique effects of prenatal opioid exposure on the early development of fine motor and communication skills. Similar findings were obtained for prescribed and illicit opioid use, underscoring developmental risks of both MAT and untreated substance use. Exploratory analyses investigating type and timing of MAT suggest directions for future research.
Collapse
Affiliation(s)
- Madelyn H Labella
- Department of Psychological & Brain Sciences, University of Delaware, 108 Wolf Hall, Newark, DE 19716, United States.
| | - Rina D Eiden
- Department of Psychology, Penn State University, 140 Moore Building, University Park, PA 16801, United States
| | - Alexandra R Tabachnick
- Department of Psychological & Brain Sciences, University of Delaware, 108 Wolf Hall, Newark, DE 19716, United States
| | - Tabitha Sellers
- Department of Psychological & Brain Sciences, University of Delaware, 108 Wolf Hall, Newark, DE 19716, United States
| | - Mary Dozier
- Department of Psychological & Brain Sciences, University of Delaware, 108 Wolf Hall, Newark, DE 19716, United States
| |
Collapse
|
|
8
|
Velasco B, Mohamed E, Sato-Bigbee C. Endogenous and exogenous opioid effects on oligodendrocyte biology and developmental brain myelination. Neurotoxicol Teratol 2021; 86:107002. [PMID: 34126203 DOI: 10.1016/j.ntt.2021.107002] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 05/26/2021] [Accepted: 06/09/2021] [Indexed: 12/27/2022]
Abstract
The elevated presence of opioid receptors and their ligands throughout the developing brain points to the existence of maturational functions of the endogenous opioid system that still remain poorly understood. The alarmingly increasing rates of opioid use and abuse underscore the urgent need for clear identification of those functions and the cellular bases and molecular mechanisms underlying their physiological roles under normal and pathological conditions. This review is focused on current knowledge on the direct and indirect regulatory roles that opioids may have on oligodendrocyte development and their generation of myelin, a complex insulating membrane that not only facilitates rapid impulse conduction but also participates in mechanisms of brain plasticity and adaptation. Information is examined in relation to the importance of endogenous opioid function, as well as direct and indirect effects of opioid analogues, which like methadone and buprenorphine are used in medication-assisted therapies for opioid addiction during pregnancy and pharmacotherapy in neonatal abstinence syndrome. Potential opioid effects are also discussed regarding late myelination of the brain prefrontal cortex in adolescents and young adults. Such knowledge is fundamental for the design of safer pharmacological interventions for opioid abuse, minimizing deleterious effects in the developing nervous system.
Collapse
Affiliation(s)
- Brandon Velasco
- Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
| | - Esraa Mohamed
- Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
| | - Carmen Sato-Bigbee
- Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
| |
Collapse
|
|
9
|
Kumar N, Rocha FG, Moustafa ASZ, Masten M, Bruder A, Parmar K, Adekola H, Sampath V, Monga R. Impact of opioid maintenance treatment during pregnancy on neonatal birth weight and head circumference. J Neonatal Perinatal Med 2021; 14:475-484. [PMID: 33843703 DOI: 10.3233/npm-200645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Pregnant mothers with opioid dependency commonly receive maintenance treatment of opioid (OMT), either as buprenorphine (BMT) or methadone maintenance treatment (MMT). We investigated, whether OMT adversely affects standardized neonatal anthropometric outcomes and whether BMT is potentially safer than MMT in this regard. METHODS Retrospective chart review of mother infant dyad, with and without OMT. Infant's absolute and standardized (z-score) anthropometric outcomes at birth were first compared, between OMT and control group (negative meconium drug screen), and then between BMT and MMT group. These outcomes were also compared between infants who did or did not require treatment after birth for neonatal abstinence syndrome (NAS). RESULT A total of 1479 participants with MDS were included [Control = 1251; OMT = 228 (MMT = 181; BMT = 47)]. Both the z-scores of birth weight (BW) and head circumference (HC) was lower in OMT group (p < 0.001). Among the OMT group, GA at delivery was slightly higher in the BMT group (p = 0.05). There was an inverse correlation between maternal dose at the time of delivery and anthropometric z-scores in the BMT group, mainly in female infants (BW: p = 0.006; HC: p = 0.003). Furthermore, In BMT group, infants with lower HC were more likely to require treatment for NAS (p = 0.01). CONCLUSION HC and BW when comparing Z-scores were not different between MMT and BMT. High maternal dosing of buprenorphine is associated with lower BW and HC Z-scores but dose effect is not seen with methadone. In addition, there seems to be an association between NAS severity and HC, especially in the BMT group.
Collapse
Affiliation(s)
- N Kumar
- Division of Neonatology, Hurley Medical Center, Flint, MI, USA
| | - F G Rocha
- Division of Maternal-Fetal Medicine, University of California, San Francisco, CA, USA
| | - A S Z Moustafa
- Department of Obstetrics and Gynecology, Hurley Medical Center, Flint, MI, USA
| | - M Masten
- Department of Obstetrics and Gynecology, Hurley Medical Center, Flint, MI, USA
| | - A Bruder
- Department of Pediatrics, Hurley Medical Center, Flint, MI, USA
| | - K Parmar
- Department of Pediatrics, Hurley Medical Center, Flint, MI, USA
| | - H Adekola
- Division of Maternal-Fetal Medicine, Southern Illinois University, Springfield, IL, USA
| | - V Sampath
- Division of Neonatology, Children's Mercy Hospital, Kansas City, MO, USA
| | - R Monga
- Division of Neonatology, Hurley Medical Center, Flint, MI, USA
| |
Collapse
|
|
10
|
Minozzi S, Amato L, Jahanfar S, Bellisario C, Ferri M, Davoli M. Maintenance agonist treatments for opiate-dependent pregnant women. Cochrane Database Syst Rev 2020; 11:CD006318. [PMID: 33165953 PMCID: PMC8094273 DOI: 10.1002/14651858.cd006318.pub4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND The prevalence of opiate use among pregnant women can range from 1% to 2% to as high as 21%. Just in the United States alone, among pregnant women with hospital delivery, a fourfold increase in opioid use is reported from 1999 to 2014 (Haight 2018). Heroin crosses the placenta, and pregnant, opiate-dependent women experience a six-fold increase in maternal obstetric complications such as low birth weight, toxaemia, third trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neuro-behavioural problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome. This is an updated version of the original Cochrane Review first published in 2008 and last updated in 2013. OBJECTIVES To assess the effectiveness of any maintenance treatment alone or in combination with a psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions alone for child health status, neonatal mortality, retaining pregnant women in treatment, and reducing the use of substances. SEARCH METHODS We updated our searches of the following databases to February 2020: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA Randomised controlled trials which assessed the efficacy of any pharmacological maintenance treatment for opiate-dependent pregnant women. DATA COLLECTION AND ANALYSIS We used the standard methodological procedures expected by Cochrane. MAIN RESULTS We found four trials with 271 pregnant women. Three compared methadone with buprenorphine and one methadone with oral slow-release morphine. Three out of four studies had adequate allocation concealment and were double-blind. The major flaw in the included studies was attrition bias: three out of four had a high dropout rate (30% to 40%), and this was unbalanced between groups. Methadone versus buprenorphine: There was probably no evidence of a difference in the dropout rate from treatment (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.37 to 1.20, three studies, 223 participants, moderate-quality evidence). There may be no evidence of a difference in the use of primary substances between methadone and buprenorphine (RR 1.81, 95% CI 0.70 to 4.68, two studies, 151 participants, low-quality evidence). Birth weight may be higher in the buprenorphine group in the two trials that reported data MD;-530.00 g, 95%CI -662.78 to -397.22 (one study, 19 particpants) and MD: -215.00 g, 95%CI -238.93 to -191.07 (one study, 131 participants) although the results could not be pooled due to very high heterogeneity (very low-quality of evidence). The third study reported that there was no evidence of a difference. We found there may be no evidence of a difference in the APGAR score (MD: 0.00, 95% CI -0.03 to 0.03, two studies,163 participants, low-quality evidence). Many measures were used in the studies to assess neonatal abstinence syndrome. The number of newborns treated for neonatal abstinence syndrome, which is the most critical outcome, may not differ between groups (RR 1.19, 95% CI 0.87 to1.63, three studies, 166 participants, low-quality evidence). Only one study which compared methadone with buprenorphine reported side effects. We found there may be no evidence of a difference in the number of mothers with serious adverse events (AEs) (RR 1.69, 95% CI 0.75 to 3.83, 175 participants, low-quality evidence) and we found there may be no difference in the numbers of newborns with serious AEs (RR 4.77, 95% CI 0.59, 38.49,131 participants, low-quality evidence). Methadone versus slow-release morphine: There were no dropouts in either treatment group. Oral slow-release morphine may be superior to methadone for abstinence from heroin use during pregnancy (RR 2.40, 95% CI 1.00 to 5.77, one study, 48 participants, low-quality evidence). In the comparison between methadone and slow-release morphine, no side effects were reported for the mother. In contrast, one child in the methadone group had central apnoea, and one child in the morphine group had obstructive apnoea (low-quality evidence). AUTHORS' CONCLUSIONS Methadone and buprenorphine may be similar in efficacy and safety for the treatment of opioid-dependent pregnant women and their babies. There is not enough evidence to make conclusions for the comparison between methadone and slow-release morphine. Overall, the body of evidence is too small to make firm conclusions about the equivalence of the treatments compared. There is still a need for randomised controlled trials of adequate sample size comparing different maintenance treatments.
Collapse
Affiliation(s)
- Silvia Minozzi
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| | - Laura Amato
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| | - Shayesteh Jahanfar
- Department of Public Health, School of Population and Public Health, University of British Columbia, Vancouver, Canada
- School of Health Sciences, Central Michigan University, Mount Pleasant, Michigan, USA
- MPH Program, School of Public Health, Central Michigan University, Michigan, USA
| | - Cristina Bellisario
- CPO Piemonte, Dipartimento Interaziendale di Prevenzione Secondaria dei Tumori S.C. Epidemiologia dei Tumori, AO Città della Salute e della Scienza di Torino Via San Francesco da Paola 31, Torino, Italy
| | - Marica Ferri
- Best practices, knowledge exchange and economic issues, European Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal
| | - Marina Davoli
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| |
Collapse
|
|
11
|
Link HM, Jones H, Miller L, Kaltenbach K, Seligman N. Buprenorphine-naloxone use in pregnancy: a systematic review and metaanalysis. Am J Obstet Gynecol MFM 2020; 2:100179. [PMID: 33345863 DOI: 10.1016/j.ajogmf.2020.100179] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 07/01/2020] [Indexed: 11/29/2022]
Abstract
OBJECTIVE The goal of this systematic review and metaanalysis is to compare pregnancy outcomes between pregnant women undergoing treatment for opioid use disorder with buprenorphine-naloxone and those undergoing treatment for opioid use disorder with other forms of medication-assisted treatment. STUDY DESIGN PubMed, Embase, PsycINFO, Cochrane Clinical Trials, and Web of Science were searched to identify studies assessing the relationship between maternal buprenorphine-naloxone use and pregnancy outcomes. Outcomes assessed included neonatal abstinence syndrome diagnosis and treatment, neonatal intensive care unit admission, length of neonatal hospital stay, delivery complications, mode of delivery, labor analgesia, illicit drug use, medication-assisted treatment dosage, gestational age at delivery, breastfeeding status, miscarriage, congenital anomalies, intrauterine fetal demise, birthweight, head circumference, length, and Apgar scores. RESULTS Overall, 5 studies comprising 6 study groups met the inclusion criteria. Of the 1875 mother-baby dyads available for analysis, medications prescribed as part of the medication-assisted treatment included buprenorphine-naloxone, buprenorphine alone, methadone, or long-acting opioids. There were no serious adverse maternal or neonatal outcomes associated with maternal buprenorphine-naloxone use reported among any of the studies. Women prescribed with buprenorphine-naloxone for delivered neonates who were less likely to require treatment for neonatal abstinence syndrome were compared with pregnant women prescribed with other opioid agonist medications. Of the remaining outcomes assessed, metaanalysis did not detect any statistically significant differences when comparing the groups of women using buprenorphine-naloxone with the groups of women prescribed with other medications as part of the medication-assisted treatment. CONCLUSION Pregnant women undergoing treatment for opioid use disorder with buprenorphine-naloxone do not experience significantly different pregnancy outcomes than women undergoing treatment with other forms of opioid agonist medication-assisted therapy.
Collapse
Affiliation(s)
| | - Hendree Jones
- Department of Obstetrics & Gynecology, University of North Carolina, Raleigh, NC
| | - Lauren Miller
- Department of Pediatrics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA
| | | | - Neil Seligman
- Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, University of Rochester Medical Center, Rochester, NY
| |
Collapse
|
|
12
|
Ward C, Christensen CW. Methadone for Opioid Use Treatment during Pregnancy: Trends in Postpartum Dose Adjustments. AJP Rep 2020; 10:e202-e209. [PMID: 33094005 PMCID: PMC7571562 DOI: 10.1055/s-0040-1713787] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 04/06/2020] [Indexed: 12/05/2022] Open
Abstract
Objective This study examines methadone dose adjustment postpartum. Methods A retrospective study of women with methadone for opioid use treatment (OUT) during pregnancy was performed. Patient charts were reviewed and data were extracted. Methadone doses from five temporal data points for each patient were used: starting dose, day of delivery, and 1, 2, and 6 months postpartum. Results Over 26 months, 49 pregnancies to women using methadone for OUT were evaluated and 20 (41%) were included. The mean methadone starting dose was 47 mg, compared with 86 mg at the time of delivery. The mean dose postpartum remained unchanged from delivery and 75% of pregnancies required the same dose or higher 1 month postpartum. By 2 months postpartum, only 33% were able to decrease their methadone dose. Twelve pregnancies completed follow-up until 6 months postpartum; only 17% of patients were able to decrease their dose, with an overall mean dose decrease was 12%. There was no difference between the mean dose at delivery and the 6-month postpartum dose. Conclusion Patients using methadone for OUT during pregnancy achieved minimal dose decreases postpartum. Patients should be counseled that postpartum dose tapers may be challenging and about alternatives to methadone for OUT.
Collapse
Affiliation(s)
- Clara Ward
- Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center/McGovern Medical School, Houston, Texas
| | - Carl W Christensen
- Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan
| |
Collapse
|
|
13
|
Delivery dose of methadone, but not buprenorphine, is associated with the risk and severity of neonatal opiate withdrawal syndrome. Am J Obstet Gynecol MFM 2019; 2:100075. [PMID: 33345989 DOI: 10.1016/j.ajogmf.2019.100075] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 11/21/2019] [Accepted: 12/02/2019] [Indexed: 11/20/2022]
Abstract
BACKGROUND Data on the relationship between the dose of opioid replacement therapy in pregnancy and the risk and severity of neonatal opioid withdrawal syndrome are conflicting and have methodological limitations. OBJECTIVE To assess the association of methadone and buprenorphine dose at delivery with neonatal opioid withdrawal syndrome in a large cohort. STUDY DESIGN We performed a retrospective cohort study using data from a comprehensive perinatal opioid dependency program from 2000 through 2016. Women with a history of opioid use disorder enrolled in a medication-assisted treatment program were included. Strict neonatal opioid withdrawal syndrome case definition and neonatal treatment guidelines were utilized throughout the study epoch. Comparisons were made between women on methadone and buprenorphine. The dose of opioid replacement at delivery and the risk and severity of neonatal opioid withdrawal syndrome were assessed with univariable analysis and multivariable logistic regression. In all analyses, methadone and buprenorphine dosing were evaluated as a continuous variable. RESULTS Four hundred eighty two of 709 women (68.0%) met inclusion criteria including 344 on methadone (71.4%) and 138 on buprenorphine (28.6%). Nonopioid polysubstance abuse, body mass index, medication-assisted treatment compliance, birthweight, and other characteristics were similar between groups. Overall, the frequency of neonatal opioid withdrawal syndrome was not significantly different between the methadone and buprenorphine groups (56.8% vs 52.0%, P = .35). Dose at delivery ranged at 0-165 mg for methadone and 0-30 mg for buprenorphine. In a univariable analysis, methadone dose at delivery was associated with neonatal opioid withdrawal syndrome (83.0 ± 34.2 mg vs 71.9 ± 35.8 mg for neonatal opioid withdrawal syndrome vs nonneonatal opioid withdrawal syndrome neonates, P < .001), but buprenorphine dose at delivery was not (8.4 ± 4.4 vs 7.6 ± 4.8 mg for neonatal opioid withdrawal syndrome vs nonneonatal opioid withdrawal syndrome neonates, P = .30). Peak neonatal opioid withdrawal syndrome score, duration of neonatal opioid withdrawal syndrome treatment, and cumulative neonatal morphine exposure were significantly associated with delivery methadone dose but not buprenorphine dose. The association between delivery methadone dose and neonatal opioid withdrawal syndrome persisted in multivariable regression. CONCLUSION The dose of methadone at the time of delivery is associated with the frequency and severity of neonatal opioid withdrawal syndrome, with higher doses associated with more severe neonatal opioid withdrawal syndrome when analyzed continuously. These data may inform future prospective studies on methadone dosing in pregnancy. While medication-assisted treatment agent and dose may have an impact on pertinent neonatal outcomes related to neonatal opioid withdrawal syndrome, the provision of medication-assisted treatment in pregnancy should reflect the goal of prevention of recidivism and maternal mortality and utilize an approach that balances fetal and maternal risk to optimize outcomes.
Collapse
|
|
14
|
Guttmann A, Blackburn R, Amartey A, Zhou L, Wijlaars L, Saunders N, Harron K, Chiu M, Gilbert R. Long-term mortality in mothers of infants with neonatal abstinence syndrome: A population-based parallel-cohort study in England and Ontario, Canada. PLoS Med 2019; 16:e1002974. [PMID: 31770382 PMCID: PMC6879118 DOI: 10.1371/journal.pmed.1002974] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/21/2019] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Opioid addiction is a major public health threat to healthy life expectancy; however, little is known of long-term mortality for mothers with opioid use in pregnancy. Pregnancy and delivery care are opportunities to improve access to addiction and supportive services. Treating neonatal abstinence syndrome (NAS) as a marker of opioid use during pregnancy, this study reports long-term maternal mortality among mothers with a birth affected by NAS in relation to that of mothers without a NAS-affected birth in 2 high-prevalence jurisdictions, England and Ontario, Canada. METHODS AND FINDINGS We conducted a population-based study using linked administrative health data to develop parallel cohorts of mother-infant dyads in England and Ontario between 2002 and 2012. The study population comprised 13,577 and 4,966 mothers of infants with NAS and 4,205,675 and 929,985 control mothers in England and Ontario, respectively. Death records captured all-cause maternal mortality after delivery through March 31, 2016, and cause-specific maternal mortality to December 31, 2014. The primary exposure was a live birth of an infant with NAS, and the main outcome was all deaths among mothers following their date of delivery. We modelled the association between NAS and all-cause maternal mortality using Cox regression, and the cumulative incidence of cause-specific mortality within a competing risks framework. All-cause mortality rates, 10-year cumulative incidence risk of death, and crude and age-adjusted hazard ratios were calculated. Estimated crude 10-year mortality based on Kaplan-Meier curves in mothers of infants with NAS was 5.1% (95% CI 4.7%-5.6%) in England and 4.6% (95% CI 3.8%-5.5%) in Ontario versus 0.4% (95% CI 0.41%-0.42%) in England and 0.4% (95% CI 0.38%-0.41%) in Ontario for controls (p < 0.001 for all comparisons). Survival curves showed no clear inflection point or period of heightened risk. The crude hazard ratio for all-cause mortality was 12.1 (95% 11.1-13.2; p < 0.001) in England and 11.4 (9.7-13.4; p < 0.001) in Ontario; age adjustment did not reduce the hazard ratios. The cumulative incidence of death was higher among NAS mothers than controls for almost all causes of death. The majority of deaths were by avoidable causes, defined as those that are preventable, amenable to care, or both. Limitations included lack of direct measures of maternal opioid use, other substance misuse, and treatments or supports received. CONCLUSIONS In this study, we found that approximately 1 in 20 mothers of infants with NAS died within 10 years of delivery in both England and Canada-a mortality risk 11-12 times higher than for control mothers. Risk of death was not limited to the early postpartum period targeted by most public health programs. Policy responses to the current opioid epidemic require effective strategies for long-term support to improve the health and welfare of opioid-using mothers and their children.
Collapse
Affiliation(s)
- Astrid Guttmann
- ICES, Toronto, Ontario, Canada
- Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Ruth Blackburn
- UCL Institute of Health Informatics, London, United Kingdom
| | | | | | - Linda Wijlaars
- UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Natasha Saunders
- ICES, Toronto, Ontario, Canada
- Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Katie Harron
- UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Maria Chiu
- ICES, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Ruth Gilbert
- UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| |
Collapse
|
|
15
|
Associations between Orofacial Clefting and Neonatal Abstinence Syndrome. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2019; 7:e2095. [PMID: 30859050 PMCID: PMC6382228 DOI: 10.1097/gox.0000000000002095] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 11/07/2018] [Indexed: 12/21/2022]
Abstract
Background: Orofacial clefting (OFC) is the most common developmental craniofacial malformation, and causal etiologies largely remain unknown. The opioid crisis has led to a large proportion of infants recovering from neonatal abstinence syndrome (NAS) due to in-utero narcotics exposure. We sought to characterize the prevalence of OFC in infants with NAS. Methods: This cohort study analyzed live births at our institution from 2013 to 2017 to identify any association between OFC and NAS. Results: Prevalence of OFC was 6.79 and 1.63 (per 1,000 live births) in the NAS and general population, respectively. Odds ratios for NAS patients having developed OFC, isolated cleft palate, isolated cleft lip, and combined cleft lip and palate compared with the general population were found to be 4.18 (P = 0.001), 5.92 (P = 0.001), 3.79 (P = 0.05), and 2.94 (P = 0.35), respectively. Analyses performed comparing the NAS and general populations to control for potential confounding variables influencing the NAS population yielded no significant differences with exception of in-utero exposure to physician prescribed opioids. Conclusions: Prevalence of OFC in infants with NAS was higher than the general live birth population. Isolated cleft palate and isolated cleft lip, specifically, were significantly more prevalent in NAS patients compared with the general population and were associated with in-utero opioid exposure.
Collapse
|
|
16
|
Does Maternal Buprenorphine Dose Affect Severity or Incidence of Neonatal Abstinence Syndrome? J Addict Med 2018; 12:435-441. [DOI: 10.1097/adm.0000000000000427] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
|
|
17
|
Tan KZ, Cunningham AM, Joshi A, Oei JL, Ward MC. Expression of kappa opioid receptors in developing rat brain - Implications for perinatal buprenorphine exposure. Reprod Toxicol 2018; 78:81-89. [PMID: 29635048 DOI: 10.1016/j.reprotox.2018.04.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 04/03/2018] [Accepted: 04/06/2018] [Indexed: 12/19/2022]
Abstract
Buprenorphine, a mu opioid receptor partial agonist and kappa opioid receptor (KOR) antagonist, is an emerging therapeutic agent for maternal opioid dependence in pregnancy and neonatal abstinence syndrome. However, the endogenous opioid system plays a critical role in modulating neurodevelopment and perinatal buprenorphine exposure may detrimentally influence this. To identify aspects of neurodevelopment vulnerable to perinatal buprenorphine exposure, we defined KOR protein expression and its cellular associations in normal rat brain from embryonic day 16 to postnatal day 23 with double-labelling immunohistochemistry. KOR was expressed on neural stem and progenitor cells (NSPCs), choroid plexus epithelium, subpopulations of cortical neurones and oligodendrocytes, and NSPCs and subpopulations of neurones in postnatal hippocampus. These distinct patterns of KOR expression suggest several pathways vulnerable to perinatal buprenorphine exposure, including proliferation, neurogenesis and neurotransmission. We thus suggest the cautious use of buprenorphine in both mothers and infants until its impact on neurodevelopment is better defined.
Collapse
Affiliation(s)
- Kathleen Z Tan
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Randwick, NSW 2031, Australia
| | - Anne M Cunningham
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Randwick, NSW 2031, Australia; Westfield Research Laboratories, Sydney Children's Hospital, High Street, Randwick, NSW 2031, Australia.
| | - Anjali Joshi
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Randwick, NSW 2031, Australia; Westfield Research Laboratories, Sydney Children's Hospital, High Street, Randwick, NSW 2031, Australia
| | - Ju Lee Oei
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Randwick, NSW 2031, Australia; The Royal Hospital for Women, Barker Street, Randwick, NSW 2031, Australia
| | - Meredith C Ward
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Randwick, NSW 2031, Australia; The Royal Hospital for Women, Barker Street, Randwick, NSW 2031, Australia; Westfield Research Laboratories, Sydney Children's Hospital, High Street, Randwick, NSW 2031, Australia.
| |
Collapse
|
|
18
|
Ordean A, Wong S, Graves L. No. 349-Substance Use in Pregnancy. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2018; 39:922-937.e2. [PMID: 28935057 DOI: 10.1016/j.jogc.2017.04.028] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
OBJECTIVES 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 the 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 Updates in the literature were retrieved through searches of Medline, PubMed, and The Cochrane Library published from 1996 to 2016 using the following key words: pregnancy, electronic cigarettes, tobacco use cessation products, buprenorphine, and methadone. Results were initially restricted to systematic reviews and RCTs/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. VALUES The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report. 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 lead to reduced health care costs and decreased maternal and neonatal morbidity and mortality. RECOMMENDATIONS
Collapse
|
|
19
|
Velez ML, McConnell K, Spencer N, Montoya L, Tuten M, Jansson LM. Prenatal buprenorphine exposure and neonatal neurobehavioral functioning. Early Hum Dev 2018; 117:7-14. [PMID: 29223912 DOI: 10.1016/j.earlhumdev.2017.11.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Revised: 11/15/2017] [Accepted: 11/21/2017] [Indexed: 11/16/2022]
Abstract
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.
Collapse
Affiliation(s)
- Martha L Velez
- Johns Hopkins University School of Medicine, Department of Pediatrics, United States.
| | - Krystle McConnell
- Johns Hopkins University School of Medicine, Department of Pediatrics, United States
| | - Nancy Spencer
- Johns Hopkins Bayview Hospital, Department of Nursing, United States
| | - Lina Montoya
- University of California at Berkeley, Department of Biostatistics, United States
| | - Michelle Tuten
- University of Maryland School of Social Work, United States
| | - Lauren M Jansson
- Johns Hopkins University School of Medicine, Department of Pediatrics, United States
| |
Collapse
|
|
20
|
Pochard L, Dupouy J, Frauger E, Giocanti A, Micallef J, Lapeyre-Mestre M. Impact of pregnancy on psychoactive substance use among women with substance use disorders recruited in addiction specialized care centers in France. Fundam Clin Pharmacol 2018; 32:188-197. [PMID: 29337399 DOI: 10.1111/fcp.12346] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 12/04/2017] [Accepted: 12/22/2017] [Indexed: 01/23/2023]
Abstract
Pregnancy can be a motivation for decrease in drug abusing but may also represent a period of high vulnerability for relapse. We aimed to assess psychoactive substance use among women with substance use disorders followed in addiction care centers in France. We analyzed data from women aged 15-44 years included in the 'Observation of illegal drugs and misuse of psychotropic medication (OPPIDUM) survey', an annual cross-sectional survey collecting details on psychoactive substances used. Characteristics of women included in 2005-2012 yearly surveys were compared depending on their pregnant or not pregnant status. Factors, including pregnancy, associated with illicit substance use and medication misuse were investigated through logistic regression. The study included 518 pregnant and 6345 nonpregnant women; 85.3% pregnant women were on opioid maintenance therapy (OMT) (vs. 77.1% of nonpregnant). Pregnancy was associated with lower illicit substance use (adjusted OR 0.71 [0.58-0.88]) and with lower medication misuse (0.66 [0.49-0.89]), whereas financial insecurity and living as a couple were associated with increased risk. Raising children was significantly associated with less risk of substance use. Each substance taken separately, the part of women using illicit substance or misusing medication did not differ depending on whether they were pregnant or not, except for heroin (24.5% in pregnant vs. 17.9% nonpregnant; <0.001). This nationwide study provides new insights into psychoactive substance use in a large mixed population of women with drug use disorders. Results outline the challenge of preventing drug use and initiating care strategies with a specific approach on socio-economic environment.
Collapse
Affiliation(s)
- Liselotte Pochard
- Service de Pharmacologie Clinique, Faculté de Médecine, Centre d'Evaluation et d'Information sur la Pharmacodépendance-Addictovigilance de Toulouse, CHU de Toulouse, 37 allées Jules Guesde, 31000, Toulouse, France.,Service de Pharmacologie Clinique et Pharmacovigilance, Centre d'Evaluation et d'Information sur la Pharmacodépendance Paca Corse, Hôpital de la Timone, 13005, Marseille, France
| | - Julie Dupouy
- Faculté de Médecine, UMR Inserm 1027, Université Toulouse 3, 37 Allées Jules Guesde, 31073, Toulouse Cedex, France
| | - Elisabeth Frauger
- Service de Pharmacologie Clinique et Pharmacovigilance, Centre d'Evaluation et d'Information sur la Pharmacodépendance Paca Corse, Hôpital de la Timone, 13005, Marseille, France.,Institut de Neurosciences de la Timone, UMR 7289 CNRS, Aix-Marseille Université, Campus Timone, 13005, Marseille, France
| | - Adeline Giocanti
- Service de Pharmacologie Clinique et Pharmacovigilance, Centre d'Evaluation et d'Information sur la Pharmacodépendance Paca Corse, Hôpital de la Timone, 13005, Marseille, France
| | - Joëlle Micallef
- Service de Pharmacologie Clinique et Pharmacovigilance, Centre d'Evaluation et d'Information sur la Pharmacodépendance Paca Corse, Hôpital de la Timone, 13005, Marseille, France.,Institut de Neurosciences de la Timone, UMR 7289 CNRS, Aix-Marseille Université, Campus Timone, 13005, Marseille, France
| | - Maryse Lapeyre-Mestre
- Service de Pharmacologie Clinique, Faculté de Médecine, Centre d'Evaluation et d'Information sur la Pharmacodépendance-Addictovigilance de Toulouse, CHU de Toulouse, 37 allées Jules Guesde, 31000, Toulouse, France.,Faculté de Médecine, UMR Inserm 1027, Université Toulouse 3, 37 Allées Jules Guesde, 31073, Toulouse Cedex, France
| | | |
Collapse
|
|
21
|
Jansson LM, Velez ML, McConnell K, Spencer N, Tuten M, Jones H, Rios R, King VL, Gandotra N, Millio L, DiPietro JA. Maternal buprenorphine treatment and infant outcome. Drug Alcohol Depend 2017; 180:56-61. [PMID: 28869859 PMCID: PMC5788458 DOI: 10.1016/j.drugalcdep.2017.08.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 07/19/2017] [Accepted: 08/01/2017] [Indexed: 01/31/2023]
Abstract
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.
Collapse
Affiliation(s)
| | | | | | | | | | - Hendree Jones
- University of North Carolina Chapel Hill, Chapel Hill, NC
| | - Rebeca Rios
- Johns Hopkins University School of Medicine, Baltimore, MD
| | - Van L. King
- Johns Hopkins University School of Medicine, Baltimore, MD
| | | | | | | |
Collapse
|
|
22
|
Chavan NR, Ashford KB, Wiggins AT, Lofwall MR, Critchfield AS. Buprenorphine for Medication-Assisted Treatment of Opioid Use Disorder in Pregnancy: Relationship to Neonatal Opioid Withdrawal Syndrome. AJP Rep 2017; 7:e215-e222. [PMID: 29226017 PMCID: PMC5720890 DOI: 10.1055/s-0037-1608783] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Accepted: 10/09/2017] [Indexed: 11/17/2022] Open
Abstract
Objective To examine the relationship between antepartum buprenorphine dose for medication-assisted treatment (MAT) of opioid use disorder (OUD) and incident neonatal opioid withdrawal syndrome (NOWS). Study Design We performed a prospective cohort study of pregnant women with a singleton gestation diagnosed with OUD and receiving buprenorphine for MAT at a tertiary care academic institution from July 2015 to January 2017. We divided the study cohort into two groups-pregnancies with versus without NOWS. Substance abuse patterns in pregnancy, maternal, and neonatal clinical outcomes were compared. Results The incidence of NOWS was 31.11% ( n = 28/90) in our study cohort. Pregnancies with NOWS had a significantly higher rate of benzodiazepine positive urine tests and number of positive urine drug screen (UDS) results for illicit opioids. The group without NOWS had significantly higher number of patients with an appropriate UDS result at delivery through postpartum. Rates of neonatal intensive care unit (NICU) admission, length of NICU stay, and maximum Finnegan score were significantly higher in the group with NOWS. Neither the initial (10.6 ± 5.2 versus 10.3 ± 4.8 mg, p = 0.80) nor the final buprenorphine doses (13.3 ± 5.1 versus 13.0 ± 4.6 mg, p = 0.81) were significantly different between study groups. Conclusion The occurrence of NOWS was not related to buprenorphine dose used for MAT.
Collapse
Affiliation(s)
- Niraj R Chavan
- Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, Kentucky
| | | | | | - Michelle R Lofwall
- Department of Behavioral Science and Psychiatry, Center on Drug and Alcohol Research, University of Kentucky College of Medicine, Lexington, Kentucky
| | - Agatha S Critchfield
- Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, Kentucky
| |
Collapse
|
|
23
|
N o 349 - Consommation de substances psychoactives pendant la grossesse. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2017; 39:938-956.e3. [PMID: 28935058 DOI: 10.1016/j.jogc.2017.06.026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIFS Accroître la sensibilisation à la consommation problématique de substances psychoactives pendant la grossesse et les connaissances à ce sujet, et formuler des recommandations factuelles relatives à la prise en charge de cet épineux problème clinique à l'intention de l'ensemble des fournisseurs de soins. OPTIONS La présente directive clinique analyse l'utilisation d'outils de dépistage, l'approche générale de soins et les recommandations pour la prise en charge clinique de la consommation problématique de substances psychoactives pendant la grossesse. ISSUES Recommandations factuelles pour le dépistage et la prise en charge de la consommation problématique de substances psychoactives pendant la grossesse et l'allaitement. RECHERCHE DOCUMENTAIRE La littérature à jour a été obtenue au moyen de recherches dans Medline, PubMed et la Bibliothèque Cochrane visant les articles publiés entre 1996 et 2016, avec les mots clés suivants : « pregnancy », « electronic cigarettes », « tobacco use cessation products », « buprenorphine » et « methadone ». Les résultats ont d'abord été restreints aux analyses systématiques, aux ECR et aux essais cliniques contrôlés. Ensuite, en raison de la rareté des ECR sur le sujet, des recherches d'études observationnelles ont également été menées. Les articles sélectionnés ont été limités aux études chez l'humain publiées en anglais, puis d'autres articles ont été trouvés manuellement, par l'analyse des listes de références. VALEURS La qualité des données a été évaluée au moyen des critères énoncés dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs. Les recommandations visant la pratique ont été classées conformément à la méthode décrite dans ce rapport. AVANTAGES, DéSAVANTAGES ET COûTS: La présente directive clinique a pour but d'améliorer les connaissances et le degré d'aisance des fournisseurs qui dispensent des soins aux femmes enceintes ayant un trouble de l'usage d'une substance. L'amélioration de l'accès aux soins de santé et de l'aide pour obtenir un traitement adéquat de la dépendance fait diminuer les coûts de santé et les taux de morbidité et de mortalité chez la mère et l'enfant. RECOMMANDATIONS.
Collapse
|
|
24
|
Brogly SB, Turner S, Lajkosz K, Davies G, Newman A, Johnson A, Dow K. Infants Born to Opioid-Dependent Women in Ontario, 2002-2014. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2017; 39:157-165. [PMID: 28343557 DOI: 10.1016/j.jogc.2016.11.009] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Revised: 11/01/2016] [Accepted: 11/07/2016] [Indexed: 11/24/2022]
Abstract
BACKGROUND There is a paucity of data characterizing mother-infant pairs with prenatal opioid dependence in Canada. We therefore conducted a study of relevant births in Ontario from 2002 to 2014. METHODS We used data from the Institute for Clinical Evaluative Sciences, the linked databases of coded population-based Ontario health services records. Differences in characteristics of opioid-dependent mother-neonate pairs and infant hospital costs by year were assessed using linear regression, and we calculated rates of preterm birth, low birth weight, birth defects, mortality, and neonatal abstinence syndrome. RESULTS The number of infants born to opioid-dependent women in Ontario rose from 46 in 2002 to almost 800 in 2014. Methadone was most frequently used for prenatal opioid dependence; there was little buprenorphine or buprenorphine + naloxone use. Rates of preterm birth and low birth weight were high. The proportion of neonates with neonatal abstinence syndrome (58%) was stable over the study period. The mean length of neonatal hospital stay was 13.96 days. Infant hospital costs increased from $724 774 in 2003 to $10 539 988 in 2013, and the mean cost per infant grew from $9928 to $12 917. Birth defect prevalence was 75.84/1000 live births (95% CI 68.12/1000 to 84.10/1000). The stillbirth rate was 11.39/1000 births (95% CI 8.47/1000 to 14.99/1000), and the infant mortality rate was 12.21/1000 live births (95% CI 9.16/1000 to 15.95/1000). CONCLUSION We observed a 16-fold increase in the number of mother-infant pairs affected by opioid dependence in Ontario over the past decade. Adverse birth outcome rates were high. Expanded services for opioid-dependent women and their children are needed.
Collapse
Affiliation(s)
- Susan B Brogly
- Department of Surgery, Queen's University, Kingston, ON.
| | - Suzanne Turner
- Department of Family Medicine, St. Michael's Hospital, Toronto, ON
| | | | - Greg Davies
- Department of Obstetrics and Gynaecology, Queen's University, Kingston, ON
| | - Adam Newman
- Department of Family Medicine, Queen's University, Kingston, ON
| | - Ana Johnson
- ICES Queen's, Queen's University, Kingston, ON; Department of Public Health Sciences, Queen's University, Kingston, ON
| | - Kimberly Dow
- Department of Pediatrics, Queen's University, Kingston, ON
| |
Collapse
|
|
25
|
Pharmacotherapy for Neonatal Abstinence Syndrome: Choosing the Right Opioid or No Opioid at All. Neonatal Netw 2017; 35:314-20. [PMID: 27636696 DOI: 10.1891/0730-0832.35.5.314] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Neonatal abstinence syndrome (NAS) from in utero opioid exposure has reached epidemic levels in the United States. Although nonpharmacologic therapies form the foundation of care, many neonates require pharmacotherapy. Morphine represents the most widely used first-line agent and effectively treats the symptoms of withdrawal. However, methadone or buprenorphine may facilitate earlier discharge. Although phenobarbital is traditionally used when opioids fail, clonidine may be a more appropriate adjunctive agent to minimize negative neurodevelopmental impact. Consideration of the available data allows hospitals to generate effective pharmacologic strategies to manage NAS while further research continues.
Collapse
|
|
26
|
Tran TH, Griffin BL, Stone RH, Vest KM, Todd TJ. Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women. Pharmacotherapy 2017; 37:824-839. [PMID: 28543191 DOI: 10.1002/phar.1958] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Pregnant women with opioid use disorder can be treated with methadone, buprenorphine, or naltrexone to reduce opioid use and improve retention to treatment. In this review, we compare the pregnancy outcomes of methadone, buprenorphine, and naltrexone in clinical trials and discuss the potential behavioral and developmental effects of these agents seen in offspring in animal studies. Important clinical considerations in the management of opioid use disorder in pregnant women and their infants are also discussed. Outside of pregnancy, buprenorphine is used in combination with naloxone to reduce opioid abuse and diversion. During pregnancy, however, the use of buprenorphine as a single agent is preferred to prevent prenatal naloxone exposure. Both methadone and buprenorphine are widely used to treat opioid use disorder; however, compared with methadone, buprenorphine is associated with shorter treatment duration, less medication needed to treat neonatal abstinence syndrome (NAS) symptoms, and shorter hospitalizations for neonates. Despite being the standard of care, medication-assisted treatment with methadone or buprenorphine is still underused, making it apparent that more options are necessary. Naltrexone is not a first-line treatment primarily because both detoxification and an opioid-free period are required. More research is needed to determine naltrexone safety and benefits in pregnant women. Animal studies suggest that changes in pain sensitivity, developmental processes, and behavioral responses may occur in children born to mothers receiving methadone, buprenorphine, or naltrexone and is an area that warrants future studies.
Collapse
Affiliation(s)
- Tran H Tran
- Pharmacy Practice, Midwestern University Chicago College of Pharmacy, Downers Grove, Illinois
| | - Brooke L Griffin
- Pharmacy Practice, Midwestern University Chicago College of Pharmacy, Downers Grove, Illinois
| | - Rebecca H Stone
- Pharmacy Practice, University of Georgia College of Pharmacy, Athens, Georgia
| | - Kathleen M Vest
- Pharmacy Practice, Midwestern University Chicago College of Pharmacy, Downers Grove, Illinois
| | - Timothy J Todd
- Pharmacy Practice, Midwestern University Chicago College of Pharmacy, Downers Grove, Illinois
| |
Collapse
|
|
27
|
Gibson KS, Stark S, Kumar D, Bailit JL. The relationship between gestational age and the severity of neonatal abstinence syndrome. Addiction 2017; 112:711-716. [PMID: 27886650 DOI: 10.1111/add.13703] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Revised: 04/19/2016] [Accepted: 11/21/2016] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND AIMS The relationship between gestational age at delivery and the severity of neonatal abstinence syndrome (NAS) is poorly understood. Our objective was to compare the length of pharmacotherapy and hospital stay among opioid-exposed infants born during the late pre-term, early term, full term and late term periods. DESIGN Retrospective cohort study of infants affected by NAS. SETTING MetroHealth Medical Center in Cleveland, OH, USA: an urban tertiary care hospital serving as the referral center for opioid dependency in pregnancy with a level III neonatal intensive care unit. PARTICIPANTS All deliveries complicated by maternal opioid exposure from January 2000 to October 2014; 403 were eligible to be included [n = 102 late pre-term, 34-36 weeks (LP), n = 158 early term, 37-38 weeks (ET), n = 122 full term, 39-40 weeks (FT), n = 21 late term, ≥41 weeks (LT)]. MEASUREMENTS NAS requiring pharmacotherapy with opioids and hospital stay duration were compared between gestational age cohorts. Interaction by type of maternal medication was evaluated. FINDINGS The necessity for pharmacotherapy for NAS was similar in all gestational age groups [LP n = 45/102 (44%), ET n = 65/158 (41%), FT n = 55/122 (45%), LT n = 9/21 (43%); P = 0.92]. However, the median duration of pharmacotherapy for NAS was significantly different between the groups [LP =16.0 median (interquartile range: IQR = 10.0-24.0) days, ET = 22.5 (IQR = 15.0-40.0), FT = 23.0 (IQR = 6.0-38.0), LT = 22.0 (IQR = 6.0-28.0); P = 0.02]. Neonatal intensive care unit admission for NAS (P = 0.07) and total length of stay (P = 0.27), which includes observation for NAS not requiring medication, were not different. There was no significant interaction between gestational age cohorts and maternal medication assisted treatment therapy on the need for or duration of NAS treatment. The results were unchanged when evaluated for potential confounding variables. CONCLUSIONS Gestational age (pre-term, term or late term) at birth appears to be unrelated to the need for pharmacotherapy to treat neonatal abstinence syndrome (NAS) in late pre-term and term infants. If treatment is needed it may tend to be given for longer in term than pre-term or late term infants.
Collapse
Affiliation(s)
- Kelly S Gibson
- Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, MetroHealth Medical Center-Case Western Reserve University, Cleveland, OH, USA
| | - Sydney Stark
- Case Western Reserve University, Cleveland, OH, USA
| | - Deepak Kumar
- Division of Neonatology, Department of Pediatrics, MetroHealth Medical Center-Case Western Reserve University, Cleveland, OH, USA
| | - Jennifer L Bailit
- Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, MetroHealth Medical Center-Case Western Reserve University, Cleveland, OH, USA
| |
Collapse
|
|
28
|
Sutter MB, Gopman S, Leeman L. Patient-centered Care to Address Barriers for Pregnant Women with Opioid Dependence. Obstet Gynecol Clin North Am 2017; 44:95-107. [DOI: 10.1016/j.ogc.2016.11.004] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
|
|
29
|
BROGLY SUSANB, SAIA KELLEY, HERNÁNDEZ-DIAZ SONIA, WERLER MARTHA, SEBASTIANI PAOLA. The comparative safety of buprenorphine versus methadone in pregnancy-what about confounding? Addiction 2016; 111:2130-2131. [PMID: 28075537 PMCID: PMC5571444 DOI: 10.1111/add.13551] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 08/04/2016] [Indexed: 11/29/2022]
Abstract
Preferential treatment of high-risk opioid-dependent pregnant women with methadone limits evidence of the comparative safety of buprenorphine versus methadone on infant outcomes. Adjustment for maternal characteristics that affect both treatment choices and birth outcomes is necessary to provide valid estimates of the effect of prenatal opioid agonist therapy exposure.
Collapse
Affiliation(s)
| | - KELLEY SAIA
- Obstetrics and Gynecology, Boston Medical Center, Boston, MA,
USA
| | - SONIA HERNÁNDEZ-DIAZ
- Department of Epidemiology, Harvard University T H Chan School of
Public Health, Boston, MA, USA
| | - MARTHA WERLER
- Department of Epidemiology, Boston University School of Public
Health, Boston, MA, USA
| | - PAOLA SEBASTIANI
- Department of Biostatistics, Boston University School of Public
Health, Boston, MA, USA
| |
Collapse
|
|
30
|
Zedler BK, Mann AL, Kim MM, Amick HR, Joyce AR, Murrelle EL, Jones HE. Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child. Addiction 2016; 111:2115-2128. [PMID: 27223595 PMCID: PMC5129590 DOI: 10.1111/add.13462] [Citation(s) in RCA: 167] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Revised: 02/16/2016] [Accepted: 05/06/2016] [Indexed: 12/25/2022]
Abstract
AIMS To assess the safety of buprenorphine compared with methadone to treat pregnant women with opioid use disorder. METHODS We searched PubMed, Embase and the Cochrane Library from inception to February 2015 for randomized controlled trials (RCT) and observational cohort studies (OBS) that compared buprenorphine with methadone for treating opioid-dependent pregnant women. Two reviewers assessed independently the titles and abstracts of all search results and full texts of potentially eligible studies reporting original data for maternal/fetal/infant death, preterm birth, fetal growth outcomes, fetal/congenital anomalies, fetal/child neurodevelopment and/or maternal adverse events. We ascertained each study's risk of bias using validated instruments and assessed the strength of evidence for each outcome using established methods. We computed effect sizes using random-effects models for each outcome with two or more studies. RESULTS Three RCTs (n = 223) and 15 cohort OBSs (n = 1923) met inclusion criteria. In meta-analyses using unadjusted data and methadone as comparator, buprenorphine was associated with lower risk of preterm birth [RCT risk ratio (RR) = 0.40, 95% confidence interval (CI) = 0.18, 0.91; OBS RR = 0.67, 95% CI = 0.50, 0.90], greater birth weight [RCT weighted mean difference (WMD) = 277 g, 95% CI = 104, 450; OBS WMD = 265 g, 95% CI = 196, 335] and larger head circumference [RCT WMD = 0.90 cm, 95% CI = 0.14, 1.66; OBS WMD = 0.68 cm, 95% CI = 0.41, 0.94]. No treatment differences were observed for spontaneous fetal death, fetal/congenital anomalies and other fetal growth measures, although the power to detect such differences may be inadequate due to small sample sizes. CONCLUSIONS Moderately strong evidence indicates lower risk of preterm birth, greater birth weight and larger head circumference with buprenorphine treatment of maternal opioid use disorder during pregnancy compared with methadone treatment, and no greater harms.
Collapse
Affiliation(s)
| | | | - Mimi M Kim
- Center for Biobehavioral Health Disparities Research, Division of Community Health, Duke University, Durham, NC, USA
| | | | | | | | - Hendrée E Jones
- UNC Horizons, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Departments of Psychiatry and Behavioral Sciences and Obstetrics and Gynecology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| |
Collapse
|
|
31
|
Neonatal Adaptation Issues After Maternal Exposure to Prescription Drugs: Withdrawal Syndromes and Residual Pharmacological Effects. Drug Saf 2016; 39:903-24. [DOI: 10.1007/s40264-016-0435-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
|
|
32
|
Konijnenberg C, Sarfi M, Melinder A. Mother-child interaction and cognitive development in children prenatally exposed to methadone or buprenorphine. Early Hum Dev 2016; 101:91-7. [PMID: 27614330 DOI: 10.1016/j.earlhumdev.2016.08.013] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 08/04/2016] [Accepted: 08/28/2016] [Indexed: 10/21/2022]
Abstract
OBJECTIVE To assess the influence of mother-child interaction on children's cognitive development in a group of children prenatally exposed to methadone or buprenorphine. STUDY DESIGN The study is part of a prospective longitudinal project investigating the development of children born to women in opioid maintenance therapy (OMT). The sample includes 67 children born between 2005 and 2007, 35 of which prenatally exposed to either methadone or buprenorphine and 32 non-exposed comparison children. RESULTS Both groups scored within the normal range of development. However, the OMT group scored significantly lower on measures of cognitive development and mother-child interaction compared to the comparison group. Cognitive development was found to be affected by both group status, F(1,54)=5.65, p=0.02, η(2)=0.10 and mother-child interaction F(1,54)=5.26, p=0.03, η(2)=0.09. Behavioral inhibition (statue), sensorimotor function (imitating hand positions), and short-term memory (sentences) was influenced by group status while narrative memory and vocabulary were found to be more influenced by mother-child interaction. CONCLUSIONS Different risk factors may influence different cognitive functions in children of women in OMT. Specifically, language-related cognitive skills may be more related to mother-child interaction while performance in higher cognitive functions requiring precise control over sensorimotor responses may be more sensitive to other factors such as prenatal OMT exposure, genetics, and/or prenatal exposure to other substances.
Collapse
Affiliation(s)
- Carolien Konijnenberg
- The Cognitive Developmental Research Unit, Department of Psychology, University of Oslo, Norway.
| | - Monica Sarfi
- Norwegian Centre for Addiction Research, University of Oslo, Oslo, Norway
| | - Annika Melinder
- The Cognitive Developmental Research Unit, Department of Psychology, University of Oslo, Norway
| |
Collapse
|
|
33
|
Wurst KE, Zedler BK, Joyce AR, Sasinowski M, Murrelle EL. A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings. SUBSTANCE ABUSE-RESEARCH AND TREATMENT 2016; 10:89-97. [PMID: 27679504 PMCID: PMC5026197 DOI: 10.4137/sart.s38887] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Revised: 05/10/2016] [Accepted: 05/18/2016] [Indexed: 12/23/2022]
Abstract
BACKGROUND Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. OBJECTIVE The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. METHODS Pregnant women and their corresponding births during 2005–2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher’s exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. RESULTS A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby’s father. CONCLUSIONS An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment during pregnancy. Twofold increased frequency of preterm birth [2.21 (1.11, 4,41)] and congenital malformations [2.05 (1.08, 3.87)] was observed in the methadone group, which may be partly explained by older average maternal age and differences in other measured and unmeasured confounders.
Collapse
|
|
34
|
Tsai LC, Doan TJ. Breastfeeding among Mothers on Opioid Maintenance Treatment: A Literature Review. J Hum Lact 2016; 32:521-9. [PMID: 27053175 DOI: 10.1177/0890334416641909] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2015] [Accepted: 03/08/2016] [Indexed: 11/16/2022]
Abstract
Although there is an abundance of interventional studies to increase breastfeeding rates, little is known about how to support and promote breastfeeding among mothers on opioid maintenance treatment (OMT). The studies on maternal OMT mainly focus on medication excreted in breast milk and breastfeeding benefits for infants with neonatal abstinence syndrome (NAS). We aim to review interventions to improve breastfeeding outcomes among mothers on OMT to make recommendations for practice and future research. We searched CINAHL, PubMed, PsycINFO, and the Cochrane Database of Systematic Reviews for articles, preferably experimental/quasi-experimental studies published within the past 10 years, that examined interventions to increase rates of breastfeeding initiation and duration among mothers on OMT. Nine studies met our inclusion criteria, comprising 5 categories: 4 combined obstetric and addiction care, 1 rooming-in, 1 Baby-Friendly hospital, 2 inpatient/outpatient NAS treatment, and 1 divided methadone dose. Breastfeeding rates were relatively higher for divided methadone dose (81% initiated any breastfeeding) and rooming-in (62% initiated any breastfeeding); lower in Baby-Friendly hospital (24%) and inpatient/outpatient NAS treatment (45% and 24%, respectively); and mixed in combined obstetric and addiction care programs (2 studies reported 70% and 76%; 2 studies reported 17% and 28%). Studies that included both methadone and buprenorphine did not specify breastfeeding results by medication. We recommend future research to differentiate breastfeeding types and duration by OMT medication. Qualitative studies are needed to explore maternal view on breastfeeding regarding need, barrier, and motivating factors in order to develop effective interventions to promote breastfeeding among mothers on OMT.
Collapse
Affiliation(s)
- Lillian C Tsai
- The Birth Center, San Francisco General Hospital and Trauma Center, San Francisco, CA, USA
| | - Therese Jung Doan
- School of Nursing, San Francisco State University, San Francisco, CA, USA
| |
Collapse
|
|
35
|
Brandt L, Swoboda P, Fischer G, Unger A. Monitoring neonatal abstinence syndrome in buprenorphine-exposed in vitro fertilization twins: A case study. Subst Abus 2016; 37:501-506. [PMID: 27163782 DOI: 10.1080/08897077.2016.1184738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND Prior studies have reported on the pregnancies and outcomes of in vitro fertilization (IVF) in special subpopulations; however, there is a lack of studies on opioid-exposed IVF-conceived neonates. CASE PRESENTATION A young adult IVF-pregnant woman was maintained on buprenorphine throughout pregnancy and received follow-up from the addiction clinic from estimated gestational week 32. She delivered healthy dichorionic twins via cesarean section at 38 weeks gestational age (buprenorphine dose at time of delivery: 16 mg). All maternal supervised urinalysis taken as of gestational week 32 were negative for concomitant substances (prior to treatment initiation at the addiction clinic, only self-reports of abstinence from concomitant substances were available). Both healthy children (male birth weight: 3140 g, female birth weight: 2650 g) developed an unusual course of neonatal abstinence syndrome (NAS) requiring extensive treatment (total morphine dose male: 22 mg, and female: 26.75 mg; length of treatment: 33 and 34 days, respectively; duration of hospitalization: 40 days). DISCUSSION The highly severe and long-lasting NAS in both neonates represents a very unusual course following an uneventful pregnancy, and influencing iatrogenic factors cannot be ruled out. Given the multiple variables influencing infant outcomes, this highlights the importance of high-quality, evidence-based standard operating procedures, which (1) are initiated as early as possible during pregnancy to minimize risk factors for adverse infant outcomes, such as concomitant substance use during pregnancy; (2) support the substance-dependent woman throughout the postpartum period, especially in cases of multiple and/or IVF-conceived pregnancies, where additional challenges may arise; and (3) consider the right of everyone to the enjoyment of the highest attainable standard of physical and mental health.
Collapse
Affiliation(s)
- Laura Brandt
- a Center for Public Health, Medical University of Vienna , Vienna , Austria
| | - Patrick Swoboda
- b Department of Psychiatry and Psychotherapy , Medical University of Vienna , Vienna , Austria
| | - Gabriele Fischer
- a Center for Public Health, Medical University of Vienna , Vienna , Austria.,b Department of Psychiatry and Psychotherapy , Medical University of Vienna , Vienna , Austria
| | - Annemarie Unger
- b Department of Psychiatry and Psychotherapy , Medical University of Vienna , Vienna , Austria
| |
Collapse
|
|
36
|
Methadone and buprenorphine for opioid dependence during pregnancy: a retrospective cohort study. J Addict Med 2015; 9:81-6. [PMID: 25622120 DOI: 10.1097/adm.0000000000000092] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
OBJECTIVES To compare maternal characteristics, prenatal care, and newborn outcomes in a cohort of opioid-dependent pregnant women treated with methadone versus buprenorphine. METHODS In a retrospective cohort study, 609 pregnant, opioid-dependent women were treated with methadone (n = 248) or buprenorphine (n = 361) between 2000 and 2012 at a single institution. RESULTS Mothers treated with buprenorphine were more likely to start medication before or earlier in pregnancy, had longer gestation, and gave birth to larger infants. Newborns of buprenorphine- versus methadone-maintained mothers required treatment for neonatal abstinence significantly less often and for a shorter duration. CONCLUSIONS These data suggest pregnancy outcomes with buprenorphine to treat opioid dependence during pregnancy in clinical practice are as good and often better than outcomes with methadone. These results are consistent with efficacy data from randomized clinical trials and further support the use of buprenorphine for the treatment of opioid dependence during pregnancy.
Collapse
|
|
37
|
Brogly SB, Hahn KA, Diaz SH, Werler M. Confounding of the Comparative Safety of Prenatal Opioid Agonist Therapy. JOURNAL OF ADDICTION RESEARCH & THERAPY 2015; 6:252. [PMID: 27547489 PMCID: PMC4991778 DOI: 10.4172/2155-6105.1000252] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Prenatal opioid agonist therapy with methadone or buprenorphine prevents maternal illicit opioid use and withdrawal and improves pregnancy outcomes compared to heroin use alone. Historically, methadone has been the first-line opioid agonist therapy for pregnant opioid dependent women; in recent years buprenorphine has become first-line treatment for some opioid dependent pregnant women. While there is some evidence of better outcomes in neonates exposed to buprenorphine vs. methadone, the effect of confounding from differences in women who use buprenorphine and methadone has not been carefully examined in most studies. This review explores mechanisms by which confounding can arise in measuring associations between prenatal buprenorphine vs. methadone exposure on neonatal outcomes using a graphical approach, directed acyclic graphs. The goal of this paper is to facilitate better understanding of the factors influencing neonatal abstinence syndrome and accurate assessment of the comparative safety of opioid agonist therapies on the neonate.
Collapse
Affiliation(s)
- Susan B Brogly
- Departments of Surgery and of Medicine, Queen’s University, Canada
| | - Kristen A Hahn
- Department of Epidemiology, Boston University School of Public Health, USA
| | | | - Martha Werler
- Department of Epidemiology, Boston University School of Public Health, USA
| |
Collapse
|
|
38
|
Kivistö K, Tupola S, Kivitie-Kallio S. Prenatally buprenorphine-exposed children: health to 3 years of age. Eur J Pediatr 2015; 174:1525-33. [PMID: 26003659 DOI: 10.1007/s00431-015-2562-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Revised: 05/03/2015] [Accepted: 05/06/2015] [Indexed: 11/28/2022]
Abstract
UNLABELLED Our prospective study is among the first attempts to examine the health of prenatally buprenorphine-exposed children after neonatal age and to determine the types of child maltreatment in this patient group. The study population included 102 children (61/41 Caucasian males/females) who had a positive urine screen for buprenorphine as a newborn. In addition to buprenorphine, the children were also prenatally exposed to other substances. The data were collected by pediatricians in follow-up visits until 3 years of age and from medical records. Ten prenatally buprenorphine-exposed children (10 %) had some birth defect. The study children had slightly more major anomalies than newborns on average in Finland (3.4 %). Eye disorders (nystagmus, opticus atrophy, and strabismus) occurred in 11 % of children. One child was diagnosed with hepatitis C transmission. One female died of sudden infant death syndrome (SIDS), and one male died of congenital heart disease. Pediatricians submitted altogether 70 reports to child welfare services of suspected maltreatment. Of these reports, 45 (64 %) involved medical neglect. Physical abuse was suspected in four reports. CONCLUSION We suggest that prenatally buprenorphine-exposed children have several types of problems with their health at toddler age and that they are susceptible to child maltreatment, especially to medical neglect.
Collapse
Affiliation(s)
- Kaisa Kivistö
- Social Pediatrics Outpatient Clinic, Hospital for Children and Adolescents, Helsinki University Central Hospital, HUS, P.O. Box 280, FI-00029, Helsinki, Finland. .,University of Helsinki, Helsinki, Finland.
| | - Sarimari Tupola
- Social Pediatrics Outpatient Clinic, Hospital for Children and Adolescents, Helsinki University Central Hospital, HUS, P.O. Box 280, FI-00029, Helsinki, Finland. .,University of Helsinki, Helsinki, Finland.
| | - Satu Kivitie-Kallio
- Social Pediatrics Outpatient Clinic, Hospital for Children and Adolescents, Helsinki University Central Hospital, HUS, P.O. Box 280, FI-00029, Helsinki, Finland. .,University of Helsinki, Helsinki, Finland.
| |
Collapse
|
|
39
|
Whitham JN, Spurrier NJ, Baghurst PA, Weston P, Sawyer MG. Visual evoked potential latencies of three-year-old children prenatally exposed to buprenorphine or methadone compared with non-opioid exposed children: The results of a longitudinal study. Neurotoxicol Teratol 2015; 52:17-24. [PMID: 26432025 DOI: 10.1016/j.ntt.2015.09.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 09/27/2015] [Accepted: 09/28/2015] [Indexed: 10/23/2022]
Abstract
This study compared the latency of pattern reversal visual evoked potentials (VEP) of 36-month old children exposed to opioid pharmacotherapy in utero to that of a group of non-exposed children. Pregnant women were enrolled as part of an open-label non-randomised flexible dosing longitudinal study. Participants were 21 children whose mothers were treated with buprenorphine- (n=11) or methadone-pharmacotherapy (n=10) during pregnancy, and 15 children not exposed to opioids in pregnancy. One-way between groups analyses of variance (ANOVA) were conducted to test the statistical significance of differences between the mean latencies of the peak response to two different sized checkerboard patterns (48' and 69' of retinal arc). Standard multiple regression analyses were conducted to determine whether there was a significant relationship between group status and VEP latencies after adjusting for the effect of covariates. VEP latencies ranged from 98 to 112 milliseconds (ms) for checks of 48' arc, and from 95 to 113ms for checks of 69' arc. Latencies were comparable across groups. After adjusting for covariates children prenatally exposed to methadone or buprenorphine did not differ significantly from non-opioid exposed children in their responses to either check size. Nor were there any significant differences in VEP latencies between children prenatally exposed to methadone and children prenatally exposed to buprenorphine. Head circumference (HC) was significantly associated with P100 latencies for both check sizes. Data from this controlled, non-randomised study suggest that neither buprenorphine nor methadone appear to have any long-term effects on visual maturity assessed at 36months of age.
Collapse
Affiliation(s)
- Justine N Whitham
- Discipline of Paediatrics, School of Paediatrics and Reproductive Health, The University of Adelaide, South Australia 5005, Australia; Research and Evaluation Unit, Women's and Children's Health Network, 72 King William Rd, North Adelaide, South Australia 5006, Australia.
| | - Nicola J Spurrier
- Department of Paediatrics and Child Health, Flinders University, Bedford Park, South Australia 5042, Australia; Public Health Partnership Branch, Department for Health and Ageing, SA Health, Citicentre 11 Hindmarsh Square, Adelaide 5000, South Australia, Australia.
| | - Peter A Baghurst
- Public Health Research Unit, Women's and Children's Health Network, 72 King William Rd, North Adelaide, South Australia 5006, Australia.
| | - Paul Weston
- Department of Neurology, Women's and Children's Hospital, 72 King William Rd, North Adelaide, South Australia 5006, Australia.
| | - Michael G Sawyer
- Research and Evaluation Unit, Women's and Children's Health Network, 72 King William Rd, North Adelaide, South Australia 5006, Australia.
| |
Collapse
|
|
40
|
Abstract
Opioid misuse during pregnancy is associated with negative outcomes for both mother and fetus due not only to the physiological effects of the drug but also to the associated social, medical and mental health problems that accompany illicit drug use. An interdisciplinary approach to the treatment of opioid use disorder during pregnancy is most effective. Ideally, obstetric and substance use treatment are co-located and ancillary support services are readily available. Medication-assisted treatment with methadone or buprenorphine is intrinsic to evidence-based care for the opioid-using pregnant woman. Women who are not stabilized on an opioid maintenance medication experience high rates of relapse and worse outcomes. Methadone has been the mainstay of maintenance treatment for nearly 50 years, but recent research has found that both methadone and buprenorphine maintenance treatments significantly improve maternal, fetal and neonatal outcomes. Although methadone remains the current standard of care, the field is beginning to move towards buprenorphine maintenance as a first-line treatment for pregnant women with opioid use disorder, because of its greater availability and evidence of better neonatal outcomes than methadone. However, there is some evidence that treatment dropout may be greater with buprenorphine relative to methadone.
Collapse
Affiliation(s)
- Christine M Wilder
- Addiction Sciences Division, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH, 45229, USA. .,Department of Veterans Affairs Medical Center, 3200 Vine Street, Cincinnati, OH, 45220, USA.
| | - Theresa Winhusen
- Addiction Sciences Division, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH, 45229, USA
| |
Collapse
|
|
41
|
Yazdy MM, Desai RJ, Brogly SB. Prescription Opioids in Pregnancy and Birth Outcomes: A Review of the Literature. J Pediatr Genet 2015; 4:56-70. [PMID: 26998394 PMCID: PMC4795985 DOI: 10.1055/s-0035-1556740] [Citation(s) in RCA: 122] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Accepted: 02/05/2015] [Indexed: 12/29/2022]
Abstract
Prescription opioids are used prenatally for the management of pain, as well as for opiate dependency. Opioids are known to cross the placenta and despite the evidence of possible adverse effects on fetal development, studies have consistently shown prescription opioids are among the most commonly prescribed medications and the prevalence of use is increasing among pregnant women. This article summarizes the available literature documenting potential harms associated with prescription opioid use during pregnancy, including poor fetal growth, preterm birth, birth defects, and neonatal abstinence syndrome.
Collapse
Affiliation(s)
- Mahsa M. Yazdy
- Slone Epidemiology Center at Boston University, Boston, Massachusetts, United States
| | - Rishi J. Desai
- Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
| | - Susan B. Brogly
- Department of Medicine and Surgery, Queen's University, Kingston, Ontario, Canada
| |
Collapse
|
|
42
|
Abstract
Neonatal opioid withdrawal syndrome is common due to the current opioid addiction epidemic. Infants born to women covertly abusing prescription opioids may not be identified as at risk until withdrawal signs present. Buprenorphine is a newer treatment for maternal opioid addiction and appears to result in a milder withdrawal syndrome than methadone. Initial treatment is with nonpharmacological measures including decreasing stimuli, however pharmacological treatment is commonly required. Opioid monotherapy is preferred, with phenobarbital or clonidine uncommonly needed as adjunctive therapy. Rooming-in and breastfeeding may decease the severity of withdrawal. Limited evidence is available regarding long-term effects of perinatal opioid exposure.
Collapse
|
|
43
|
Ross EJ, Graham DL, Money KM, Stanwood GD. Developmental consequences of fetal exposure to drugs: what we know and what we still must learn. Neuropsychopharmacology 2015; 40:61-87. [PMID: 24938210 PMCID: PMC4262892 DOI: 10.1038/npp.2014.147] [Citation(s) in RCA: 278] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Revised: 05/29/2014] [Accepted: 06/02/2014] [Indexed: 01/13/2023]
Abstract
Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose-response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures.
Collapse
Affiliation(s)
- Emily J Ross
- Chemical & Physical Biology Program, Vanderbilt University, Nashville, TN, USA
| | - Devon L Graham
- Department of Pharmacology, Vanderbilt University, Nashville, TN, USA
| | - Kelli M Money
- Neuroscience Graduate Program, Vanderbilt University, Nashville, TN, USA
| | - Gregg D Stanwood
- Department of Pharmacology, Vanderbilt University, Nashville, TN, USA
- The Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA
| |
Collapse
|
|
44
|
O'Connor AB, O'Brien L, Alto WA, Wong J. Does concurrent in utero exposure to buprenorphine and antidepressant medications influence the course of neonatal abstinence syndrome? J Matern Fetal Neonatal Med 2014; 29:112-4. [PMID: 25394611 DOI: 10.3109/14767058.2014.987750] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE To determine whether concurrent in utero exposure to buprenorphine and antidepressants impacts the course of neonatal abstinence syndrome (NAS) in infants. METHODS A retrospective cohort study of 148 infants who were exposed to buprenorphine during pregnancy. Univariate and bivariate analyses were used to examine associations between concurrent maternal use of buprenorphine and antidepressants as compared to maternal use of buprenorphine alone. RESULTS The time to onset of NAS resolution was significantly longer in infants exposed to both buprenorphine and antidepressants during pregnancy when compared to those exposed to buprenorphine alone (129.8 h versus 70.2 h, p = 0.042). CONCLUSIONS Women who are prescribed both antidepressants and buprenorphine during pregnancy should be counseled about the possibility of a prolonged course of neonatal abstinence syndrome.
Collapse
Affiliation(s)
- Alane B O'Connor
- a Dartmouth Medical School, Maine Dartmouth Family Medicine Residency , Waterville , ME , USA
| | - Liam O'Brien
- b Department of Mathematics and Statistics , Colby College , Waterville , ME , USA .,c School of Community and Population Health, University of New England , Portland , ME , USA , and
| | - William A Alto
- d Swedish Family Medicine Residency Program Cherry Hill, University of Washington , Seattle , WA , USA
| | - Jacqueline Wong
- d Swedish Family Medicine Residency Program Cherry Hill, University of Washington , Seattle , WA , USA
| |
Collapse
|
|
45
|
Weimer MB, Chou R. Research gaps on methadone harms and comparative harms: findings from a review of the evidence for an American Pain Society and College on Problems of Drug Dependence clinical practice guideline. THE JOURNAL OF PAIN 2014; 15:366-76. [PMID: 24685460 DOI: 10.1016/j.jpain.2014.01.496] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2013] [Revised: 01/21/2014] [Accepted: 01/21/2014] [Indexed: 01/10/2023]
Abstract
UNLABELLED Methadone-associated overdose deaths have dramatically increased. In order to inform an evidence-based clinical practice guideline to improve safety of methadone prescribing, the American Pain Society commissioned a systematic review on various aspects related to methadone safety. We searched Ovid MEDLINE, Cochrane Library, and PsycINFO databases through July 2012 to identify studies that addressed 1 or more of 17 Key Questions related to methadone safety; an update search was performed in 2014 for new studies related to methadone-related overdose and risks related to cardiac arrhythmias. A total of 168 studies met inclusion criteria for the review. The purpose of this article is to highlight critical research gaps in the literature related to methadone safety. These include lack of evidence on risk factors associated with methadone-overdose deaths and adverse events, limited evidence to evaluate the comparative mortality of methadone versus other opioids, insufficient evidence to fully understand the harms associated with methadone use during pregnancy, and insufficient evidence to determine effects of risk mitigation strategies such as electrocardiogram monitoring, strategies for managing patients with prolonged QTc intervals on screening, urine drug testing, alternative dosing regimens for initiation and titration of therapy, and timing of follow-up. Therefore, most guideline recommendations are based on weak evidence. More research is needed to guide safe methadone prescribing practices and decrease the adverse events associated with methadone. PERSPECTIVE This article summarizes critical research gaps in the literature related to methadone safety, based on a systematic review commissioned by the American Pain Society. Critical research gaps were identified in a number of areas, highlighting the need for additional research to guide safer prescribing and risk mitigation strategies.
Collapse
Affiliation(s)
- Melissa B Weimer
- Department of Medicine, Oregon Health & Science University, Portland, Oregon
| | - Roger Chou
- Department of Medicine, Oregon Health & Science University, Portland, Oregon; Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon; Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, Portland, Oregon.
| |
Collapse
|
|
46
|
Brogly SB, Saia KA, Walley AY, Du HM, Sebastiani P. Prenatal buprenorphine versus methadone exposure and neonatal outcomes: systematic review and meta-analysis. Am J Epidemiol 2014; 180:673-86. [PMID: 25150272 DOI: 10.1093/aje/kwu190] [Citation(s) in RCA: 121] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal buprenorphine maintenance treatment (BMT) versus methadone maintenance treatment (MMT) may improve neonatal outcomes, but associations vary. To summarize evidence, we used a random-effects meta-analysis model and estimated summary measures of BMT versus MMT on several outcomes. Sensitivity analyses evaluated confounding, publication bias, and heterogeneity. Subjects were 515 neonates whose mothers received BMT and 855 neonates whose mothers received MMT and who were born from 1996 to 2012 and who were included in 12 studies. The unadjusted NAS treatment risk was lower (risk ratio=0.90, 95% confidence interval (CI): 0.81, 0.98) and mean length of hospital stay shorter (-7.23 days, 95% CI: -10.64, -3.83) in BMT-exposed versus MMT-exposed neonates. In treated neonates, NAS treatment duration was shorter (-8.46 days, 95% CI: -14.48, -2.44) and morphine dose lower (-3.60 mg, 95% CI: -7.26, 0.07) in those exposed to BMT. BMT-exposed neonates had higher mean gestational age and greater weight, length, and head circumference at birth. Fewer women treated with BMT used illicit opioids near delivery (risk ratio=0.44, 95% CI: 0.28, 0.70). Simulations suggested that confounding by indication could account for some of the observed differences. Prenatal BMT versus MMT may improve neonatal outcomes, but bias may contribute to this protective association. Further evidence is needed to guide treatment choices.
Collapse
|
|
47
|
Bagley SM, Wachman EM, Holland E, Brogly SB. Review of the assessment and management of neonatal abstinence syndrome. Addict Sci Clin Pract 2014; 9:19. [PMID: 25199822 PMCID: PMC4166410 DOI: 10.1186/1940-0640-9-19] [Citation(s) in RCA: 106] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2014] [Accepted: 09/03/2014] [Indexed: 12/22/2022] Open
Abstract
Neonatal abstinence syndrome (NAS) secondary to in-utero opioid exposure is an increasing problem. Variability in assessment and treatment of NAS has been attributed to the lack of high-quality evidence to guide management of exposed neonates. This systematic review examines available evidence for NAS assessment tools, nonpharmacologic interventions, and pharmacologic management of opioid-exposed infants. There is limited data on the inter-observer reliability of NAS assessment tools due to lack of a standardized approach. In addition, most scales were developed prior to the prevalent use of prescribed prenatal concomitant medications, which can complicate NAS assessment. Nonpharmacologic interventions, particularly breastfeeding, may decrease NAS severity. Opioid medications such as morphine or methadone are recommended as first-line therapy, with phenobarbital or clonidine as second-line adjunctive therapy. Further research is needed to determine best practices for assessment, nonpharmacologic intervention, and pharmacologic management of infants with NAS in order to improve outcomes.
Collapse
Affiliation(s)
- Sarah Mary Bagley
- Section of General Internal Medicine, Boston University School of Medicine, 801 Mass Ave, 2nd Floor, Boston, MA 02118, USA.
| | | | | | | |
Collapse
|
|
48
|
Abstract
Neonatal abstinence syndrome (NAS) is a result of the sudden discontinuation of fetal exposure to substances that were used or abused by the mother during pregnancy. Withdrawal from licit or illicit substances is becoming more common among neonates in both developed and developing countries. NAS continues to be an important clinical entity throughout much of the world. NAS leads to a constellation of signs and symptoms involving multiple systems. The pathophysiology of NAS is not completely understood. Urine or meconium confirmation may assist the diagnosis and management of NAS. The Finnegan scoring system is commonly used to assess the severity of NAS; scoring can be helpful for initiating, monitoring, and terminating treatment in neonates. Nonpharmacological care is the initial treatment option, and pharmacological treatment is required if an improvement is not observed after nonpharmacological measures or if the infant develops severe withdrawal. Morphine is the most commonly used drug in the treatment of NAS secondary to opioids. An algorithmic approach to the management of infants with NAS is suggested. Breastfeeding is not contraindicated in NAS, unless the mother is taking street drugs, is involved in polydrug abuse, or is infected with HIV. Future studies are required to assess the long-term effects of NAS on children after prenatal exposure.
Collapse
Affiliation(s)
- Prabhakar Kocherlakota
- Division of Neonatology, Department of Pediatrics, Maria Fareri Children's Hospital at New York Medical College, Valhalla, New York
| |
Collapse
|
|
49
|
Gower S, Bartu A, Ilett KF, Doherty D, McLaurin R, Hamilton D. The wellbeing of infants exposed to buprenorphine via breast milk at 4 weeks of age. J Hum Lact 2014; 30:217-23. [PMID: 24399105 DOI: 10.1177/0890334413517748] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Buprenorphine has been available in Australia since 2000 as an alternative pharmacotherapy to methadone for the treatment of opioid dependence. However, there is little information in the literature regarding the effect of buprenorphine on the wellbeing of infants exposed to buprenorphine via breast milk, following discharge from hospital. OBJECTIVE The aim of the present study was to examine the wellbeing of infants exposed to buprenorphine via breast milk up to 4 weeks postnatally. METHODS Approximately 4 weeks after birth, information on the feeding and sleeping patterns, skin color, infant elimination patterns and hydration, and Neonatal Abstinence Scores of infants (n = 7) exposed to buprenorphine via breast milk was collected via both observation and documentation. RESULTS Infants were progressing well, with normal sleep patterns and skin color, and 2 mothers had minor concerns regarding infant elimination patterns. Four infants were exclusively breastfed and 3 were receiving a supplement, with a range of 260 to 700 mL of formula over 24 hours. The sleep patterns following feeding ranged from 1.55 to 3.33 hours, with a median of 2.12 hours. CONCLUSION No adverse effects were detected in infants exposed to buprenorphine via breast milk up to 4 weeks postnatally. Further research using larger samples to assess possible developmental effects over longer periods of time is required.
Collapse
Affiliation(s)
- Shelley Gower
- 1School of Nursing and Midwifery, Curtin University, Bentley, Perth, WA, Australia
| | | | | | | | | | | |
Collapse
|
|
50
|
Gawronski KM, Prasad MR, Backes CR, Lehman KJ, Gardner DK, Cordero L. Neonatal outcomes following in utero exposure to buprenorphine/naloxone or methadone. SAGE Open Med 2014; 2:2050312114530282. [PMID: 26770721 PMCID: PMC4607220 DOI: 10.1177/2050312114530282] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Accepted: 03/12/2014] [Indexed: 01/06/2023] Open
Abstract
Objectives: To study neonatal outcomes following buprenorphine/naloxone and methadone exposure during pregnancy. Methods: This study is a retrospective review of clinical and demographic information of 58 infants whose mothers were treated with buprenorphine/naloxone and 92 infants whose mothers were treated with methadone for opioid dependence during pregnancy. Results: Gestational age, birth weight, prematurity, admission to neonatal intensive care unit, and length of stay were similar between both groups of infants. Neonatal abstinence syndrome occurred less frequently among infants of mothers treated with buprenorphine/naloxone than those treated with methadone (64% and 80%, respectively, p = 0.03). All infants with neonatal abstinence syndrome were treated postnatally with methadone. There was a trend toward shorter duration of treatment and lower cumulative dosages of methadone among the buprenorphine/naloxone–exposed infants. Conclusions: No apparent significant adverse neonatal outcomes were detected following treatment with either maintenance medication; however, further prospective research is necessary to examine the safety and efficacy of buprenorphine/naloxone in pregnancy and its effects on the neonate.
Collapse
Affiliation(s)
| | - Mona R Prasad
- Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Carl R Backes
- Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - K Joy Lehman
- Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Debra K Gardner
- Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Leandro Cordero
- Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| |
Collapse
|