Opioid Replacement for Pregnant Mothers With Opioid Use Disorder and Fetal Neurodevelopment: A Review

Contenu principal de l'article

Caragh Dallas Miller
Elizabeth Nizalik
David Grynspan

Résumé

This paper reviews the published literature regarding neurodevelopmental outcomes in neonates following in utero exposure to opioids. We have summarized available clinical and experimental data. Overall, clinical data is limited and equivocal with most studies showing no significant neurodevelopmental impairments in infants and children exposed to opioids in utero. Various outcome measures assessed language, communication, cognitive, psychomotor, and behavioural outcomes. The equivocality of the data may be a result of the complexity of the cohort and the inability to disentangle the effect of the opioids from the multiple comorbidities. Results from experimental data show that all opioids cross the placental barrier. Mouse studies show biochemical and neurophysiological changes, leading to long-term effects on learning and memory. Some data also suggests that epigenetic and imprinting changes in the central nervous system of mice may lead to multigenerational effects of opioid exposure. Ultimately, the benefits of opioid replacement therapy outweigh its risks, but it should be done in the context of a broader biopsychosocial risk reduction approach. Promoting mother-child bonding and care through skin-to-skin contact, rooming-in, and breastfeeding can reduce severity of neonatal abstinence syndrome and improve outcomes. This cohort of women and children requires advocacy for comprehensive multidisciplinary care. 

Résumé

Cet article passe en revue la littérature publiée concernant les résultats neurodéveloppementaux chez les nouveau-nés après exposition in utero aux opioïdes. Nous avons résumé les données cliniques et expérimentales disponibles. Dans l’ensemble, les don- nées cliniques sont limitées et équivoques, avec la plupart des études ne montrant aucune déficience neurodéveloppementale significative chez les nourrissons et les enfants exposés aux opioïdes in utero. Diverses mesures de résultats ont évalué les résultats linguistiques, de communication, cognitifs, psychomoteurs et comportementaux. L’équivocité des données peut être le résultat de la complexité de la cohorte et de l’incapacité à démêler l’effet des opioïdes des multiples comorbidités. Les résultats des données expérimentales montrent que tous les opioïdes traversent la barrière placentaire. Les études sur la souris montrent des changements biochimiques et neurophysiologiques, conduisant à des effets à long terme sur l’apprentissage et la mémoire. Certaines données suggèrent également que les changements épigénétiques et d’empreinte dans le système nerveux central des souris peuvent conduire à des effets multigénérationnels de l’exposition aux opioïdes. En fin de compte, les avantages de la thérapie de substitution aux opioïdes l’emportent sur ses risques, mais cela devrait être fait dans le contexte d’une approche plus large de réduction des risques biopsychosociaux. La promotion des liens et des soins entre la mère et l’enfant par le contact peau à peau, l’accoutumance et l’allaitement peut réduire la gravité du syndrome d’abstinence néonatale et améliorer les résultats. Cette cohorte de femmes et d’enfants a besoin de plaidoyer pour des soins multidisciplinaires complets. 

Renseignements sur l'article

Rubrique
Review & Clinical Practice
Bibliographies de l'auteur-e

Caragh Dallas Miller, University of Ottawa School of Medicine

BSc

MD2020 Candidate 

University of Ottawa, Faculty of Medicine

Elizabeth Nizalik, Department of Pathology and Laboratory Medicine, CHEO University of Ottawa

MD, FRCPSC

Assistant Professor, Faculty of Medicine, University of Ottawa 

Department of Pathology and Laboratory Medicine, CHEO

 

David Grynspan, Department of Pathology and Laboratory Medicine, CHEO University of Ottawa

MD, FRCPSC

Assistant Professor, Faculty of Medicine, University of Ottawa 

Department of Pathology and Laboratory Medicine, CHEO

Références

1. United Nations Office on Drug and Crime. World drug report. United Nations publication. 2016.

2. Brogly SB et al. Infants Born to Opioid-Dependent Women in Ontario. JOGC. 2017;39(3):157–165.

3. American College of Obstetrics and Gynecologist. Opioid Use and Opioid Use Disorder in Pregnancy. Committee Opinion No. 711. 2017.

4. SOGC clinical practice guidelines. Substance use in pregnancy. International journal of gynecology and obstetrics. 2011;256:190-202.

5. Kaltenbach K and Finnegan LP. Perinatal and developmental outcome of infants exposed to methadone in-utero. Neurotoxicol. Teratol. 1987;9(4):311-3.

6. Reddy UM, Davis JM, Ren Z and Greene MF. Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes. Obstet. Gynecol. 2017;130(1):10–28.

7. Logan B, Brown M and Hayes M. Neonatal abstinence syndrome: treatment and pediatric outcomes. Clin. Obstet. 2013;56(1):186–192.

8. Skovlund E, Handal M, Selmer R, Brandlistuen RE and Skurtveit S. Language competence and communication skills in 3-year-old children after prenatal exposure to analgesic opioids. Pharmacoepidemiol. Drug Saf. 2017:26(6);625–634.

9. Baldacchino A, Arbuckle K, Petrie DJ and McCowan C. Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis. BMC Psychiatry. 2014;14:104.

10. Jansson, L. M. et al. Fetal neurobehavioral effects of exposure to methadone or buprenorphine. Neurotoxicol. Teratol. 33, 240–243 (2011).

11. Jansson LM et al. Maternal buprenorphine treatment and fetal neurobehavioral development. Am. J. Obstet. Gynecol. 2017;216(5):529.e1-529.e8.

12. Hans SL. Developmental Consequences of Prenatal Exposure to Methadone. Ann. N. Y. Acad. Sci. 1989;562:195–207.

13. Messinger DS. et al. The maternal lifestyle study: cognitive, motor, and behavioural outcomes of cocaine-exposed and opiate-exposwed infants through three years of age. Pediatrics. 2004;113(6):16–20.

14. Malek A and Mattison DR. Drugs and medicines in pregnancy: the placental disposition of opioids. Curr. Pharm. Biotechnol. 2011;12(5):797–803.

15. Yang SN et al. Alterations of post-synaptic density proteins in the hippocampus of rat offspring from the morphine-addicted mother: beneficial effect of dextromethorphan. Hippocampus. 2006;16(6):521-30.

16. Mithbaokar P, Fiorito F, Della Morte R, Maharajan V and Costagliola A. Chronic maternal morphine alters calbindin D-28k expression pattern in postnatal mouse brain. Synapse. 2016;70(1):15–23.

17. Amri J, Sadegh M, Moulaei N and Palizvan MR. Transgenerational modification of hippocampus TNF-α and S100B levels in the offspring of rats chronically exposed to morphine during adolescence. Am. J. Drug Alcohol Abuse. 2017:1-8.

18. Pan J, He L, Li X, Li M, Zhang X, Venesky J, Li Y, Peng Y. Activating autophagy in hippocampal cells alleviates the morphine-induced memory impairment. Mol Neurobiol. 2016;54(3):1710–1724.

19. Goldman D, Oroszi G and Ducci F. The genetics of addictions: uncovering the genes. Nat. Rev. Genet. 2005;6(7):521–532.

20. Levran O, Yuferov V and Kreek MJ. The genetics of the opioid system and specific drug addictions. Hum. Genet. 2012;131(6):823–842.

21. Wachman EM et al. Epigenetic variations in the mu-opioid receptor gene in infants with neonatal abstinence syndrome. 2015;165(3):472–478.

22. Byrnes JJ, Johnson NL, Carini LM and Byrnes EM. Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function. Psychopharmacology (Berl). 2013;227(2):263-72.

23. Dooley R et al. Narcotic tapering in pregnancy using long-acting morphine: An 18-month prospective cohort study in northwestern Ontario. Can. Fam. Physician. 2015;61(2):e88–e95.

24. Ordean A, Kahan M, Graves L, Abrahams R and Kim T. Obstetrical and Neonatal Outcomes of Methadone-Maintained Pregnant Women: A Canadian Multisite Cohort Study. J. Obstet. Gynaecol. Canada. 2015;37(3):252–257.

25. Holmes B et al. Rooming-in care for infants of opioid-dependent mothers Implementation and evaluation at a tertiary care hospital. Canadian family physician. 2015;61:555–561.

26. Goodman D. Improving Access to Maternity Care for Women with Opioid Use Disorders: Colocation of Midwifery Services at an Addiction Treatment Program. J. Midwifery Women’s Heal. 2015;60(6):706–712.