Managing infants born to mothers who have used opioids during pregnancy
Posted: May 11 2018
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Thierry Lacaze-Masmonteil, Pat O’Flaherty; Canadian Paediatric Society, Fetus and Newborn Committee
Paediatr Child Health 2018, 23(3):220–226
The incidence of infant opioid withdrawal has grown rapidly in many countries, including Canada, in the last decade, presenting significant health and early brain development concerns. Increased prenatal exposure to opioids reflects rising prescription opioid use as well as the presence of both illegal opiates and opioid-substitution therapies. Infants are at high risk for experiencing symptoms of abstinence or withdrawal that may require assessment and treatment. This practice point focuses specifically on the effect(s) of opioid withdrawal and current management strategies in the care of infants born to mothers with opioid dependency.
Keywords: Discharge planning; Management; NAS; NPI; Treatment strategies
For 2016–17, the Canadian Institute for Health Information reported that an estimated 0.51% of all infants born in Canada (approximately 1850/year, Quebec excluded) had Neonatal Abstinence Syndrome (NAS). A large percentage of these cases are attributed to opioid withdrawal . The average length of stay in acute care facilities for these infants was 15 days. Recent reports indicate the number of infants requiring observation for withdrawal symptoms is increasing annually and that cases are generally under-reported . The costs of hospitalization speak to the significant burden this problem places on the health of mothers, infants and families, along with hospital units, health care providers and other community resources .
Opioid use during pregnancy, whether prescribed or illicit, can be associated with negative pregnancy and infant outcomes, including prematurity, low birth weight, increased risk of spontaneous abortion, sudden infant death syndrome and infant neurobehavioural abnormalities . Natural compounds include morphine and codeine. Heroin, oxycodone, hydrocodone, hydromorphone and buprenorphine are semi-synthetic. Fentanyl, methadone, normethadone, tramadol and meperidine are synthetic . The most significant effects of maternal opioid dependence and prenatal fetal exposure are short-term complications, with NAS predominating. NAS is a set of drug withdrawal symptoms that can affect the central nervous system (CNS), and the gastrointestinal and respiratory systems in the newborn . Potential long-term outcomes of prenatal opiate exposure are difficult to predict due to multiple, interrelated variables of maternal-infant risk factors that are known to impact developmental outcomes in this cohort .
Pregnant women with an opioid dependence should be advised to continue or commence an opioid maintenance therapy program . Methadone is often recommended for opioid- dependent pregnant women  and some studies suggest buprenorphine as an alternative treatment . The literature reports that opioid substitution therapy during pregnancy may lessen the use of other opioids and illicit drugs and improve prenatal care, including access to education, counselling and community supportive services . Obtaining a comprehensive medication or illicit substance use history and a focused social history are recommended. Other associated health risks include infections (e.g., hepatitis B, hepatitis C, syphilis and HIV), insufficient maternal nutrition or access to antenatal care, as well as social risk factors, and should be screened for, determined and managed appropriately.
The presentation of withdrawal symptoms varies, depending on the type of maternal opioid used, the frequency, dose and timing of last exposure, gestational age, maternal metabolism and maternal use of other substances. Approximately 50% to 75% of infants born to women on opioids will require treatment for opioid withdrawal symptoms . Symptoms of opioid withdrawal (Figure 1) typically appear shortly after birth, with the majority exhibited within the first 48 h to 72 h postdelivery. Some reports suggest a later symptom presentation, at 5 to 7 days postbirth, after exposure to methadone or buprenorphine . Initial acute symptoms may persist for several weeks (ranging from 10 to 30 days) while milder symptoms, such as irritability, sleep disorders and feeding problems can persist for 4 to 6 months . Preterm infants have been described as being at lower risk for drug withdrawal and symptoms of NAS may not be as apparent as in their term counterparts . Reasons for this difference include: a shorter in utero exposure time, decreased placental transmission, inability to fully excrete drugs by immature kidneys and liver, minimal fat stores leading to lower opioid deposition and activity, as well as a limited capacity to express classic NAS symptoms by the immature brain .
Other neonatal conditions such as hypoglycemia, hypocalcemia, CNS injury, hyperthyroidism, bacterial sepsis or other infections may present with similar symptoms and should be considered as part of the differential diagnosis.
For all opioid-exposed infants, an assessment scoring system should be used to measure the severity of withdrawal symptoms and help determine whether additional monitoring, nursing, medical and pharmacological therapy are required . The most widely used scale to evaluate infants for opioid withdrawal is the Finnegan scoring system, which identifies behaviours associated with withdrawal (Figure 1) . An initial score is typically obtained within the first 1 h to 2 h postdelivery, then rechecked every 3 h to 4 h thereafter, in conjunction with other nursing assessments. Most guidelines suggest that scoring should be done for a minimum of 72 h and up to 120 h when an infant was exposed in utero to a longer-acting opioid, such as methadone or buprenorphine . The scale may also be used to assess the resolution of symptoms after initiating treatment. Accurate, consistent scoring of symptoms is necessary to ensure that the infant receives appropriate care . A variety of instructional videos and “train-the-trainer” approaches are available to ensure that staff education is consistent for proper scoring . Priorities are to develop a standardized process to identify, manage and evaluate infants with NAS, then to discharge them as soon as it is safe and appropriate.
Successful supportive management of infants exposed to opioids during pregnancy depends on a number of factors, such as providing appropriate medication(s), correct scheduling, using an accurate tool to measure and evaluate the severity of symptoms, creating a compatible physical environment and having a knowledgeable, experienced health care team. Involving interprofessional team members, (i.e., specialized in nursing, neonatal medicine, social work, pharmacy, nutrition and community resources) is essential for ensuring the seamless management and discharge of these vulnerable infants . Treatment goals include preventing complications associated with NAS and restoring normal newborn activities, such as sleep, sufficient feeding, weight gain and environmental adaptation.
In addition to maternal self-reporting, some practitioners conduct urine or meconium toxicology screens for infants born to women with a suspected history of drug abuse during pregnancy. This information may be helpful to identify the substance(s) of abuse and for selecting appropriate pharmacological treatment, when required . However, the validity and reliability of toxicology testing is controversial . Further, obtaining maternal consent for testing, securing knowledge of who will have access to the results and other legal considerations are important in the decision to conduct or send toxicology screens . National neonatal resuscitation guidelines suggest that using naloxone during infant resuscitation should be avoided when an infant is born to a known opioid-dependent mother because it has been associated with seizures in newborns . There is no evidence to suggest that a higher than routine level of health care practitioner (HCP) care competency is required at delivery, provided there are no other risk factors present.
It is well known that separating infant and mother can be detrimental to early attachment. Recent literature supports practices that keep opioid-dependent mothers and their infants together from birth, such as rooming-in. Such practices have additional benefits, such as lower neonatal intensive care unit (NICU) admissions, higher breastfeeding initiation rates, less need for pharmacotherapy and shorter hospital stays –. A rooming-in model of care—rather than admission to NICU—can be considered for mother–infant dyads at risk for developing NAS symptoms when: infants are term or near term, medically stable, and adequate resources are in place to support both the family and HCPs.
Initial treatment for neonatal withdrawal should be primarily supportive because medical interventions can prolong hospitalization, disrupt mother–infant attachment and subject an infant to drugs that may not be necessary. Nonpharmacological interventions have been shown to reduce the effects of withdrawal and should be implemented as soon as possible following birth . Examples of supportive interventions include skin-to-skin contact, safe swaddling, gentle waking, quiet environment, minimal stimulation, lower lighting, developmental positioning, music or massage therapy .
Breastfeeding should be encouraged because it can delay the onset and decrease the severity of withdrawal symptoms as well as decrease the need for pharmacological treatment . HIV-negative mothers who are stable and on opioid maintenance treatment with either methadone or buprenorphine should be encouraged to breastfeed . Breastfeeding provides optimal nutrition, promotes maternal–infant attachment and facilitates parenting competence. Mothers with a dependency who wish to breastfeed may require extra support as they are less likely to initiate breastfeeding successfully and more likely to stop breastfeeding early .
NAS infants may show impaired feeding behaviours such as excessive non-nutritive sucking, poor feeding, regurgitation and diarrhea . An early study  found that opioid- exposed infants had more feeding problems (rejecting the nipple, dribbling milk, hiccoughing, spitting up, and coughing) than nondrug-exposed infants. More recent studies have confirmed these findings and described the challenges caregivers face when feeding infants who show signs of withdrawal . Supplementation with concentrate to increase caloric intake or total fluid intake has been suggested for infants with poor weight gain .
Pharmacological therapy is indicated for infants whose withdrawal signs are increasingly severe or whose concurrent NAS scores climb despite supportive measures to reduce and manage symptoms. Infants who require treatment with medications may also require admission to a special care nursery or NICU for cardiorespiratory monitoring and observation while therapy is initiated, particularly if they are medically unstable. A stabilized infant can be transferred back into a care-by-parent area (e.g., rooming-in) provided that assessment, parent education and medication weaning monitoring are ongoing, infant–mother attachment is supported and comprehensive discharge planning can be initiated . Rooming-in with mothers on a methadone program and breastfeeding have been shown to reduce the need for pharmacological intervention .
Several pharmacological agents have been used to ameliorate symptoms associated with neonatal opioid withdrawal (Table 1). Few studies have examined pharmacotherapy efficacy. The American Academy of Pediatrics recommends matching drug selection to the type of agent causing withdrawal . Morphine and methadone remain the most common first-line medications, with lack of evidence for which agent is superior . Compared with oral morphine, sublingual buprenorphine has recently been shown to reduce length of stay in hospital by 42% in symptomatic infants born to mothers on methadone . Adjunctive use of phenobarbital or clonidine therapy to treat opioid withdrawal has been studied and implemented in some guidelines . Published guidelines provide information on initial dosing, dosing increments, initiating additional treatments and weaning, to assist in a consistent approach to management .
Length of stay in hospital varies depending on prenatal drug(s) exposure, severity of withdrawal, symptoms, treatment and social factors . Observe for a minimum of 72 h. If the treatment threshold is not reached within that time, the infant becomes eligible for discharge . The key to successful transition home is to ensure continuity of care by an interprofessional team, with anticipatory planning for when the infant meets criteria for discharge.
Individualized discharge planning should include appropriate referral to a primary health care provider familiar with pharmacological treatments for opioid withdrawal, nutritional and family supportive resources and infant neurodevelopmental assessment. Communicating with the infant’s biological (or where necessary, foster care) family and the primary HCP about the discharge plan and follow-up is essential. In some situations, when adequate medical and social follow-up is available, infants may be discharged home on pharmacological support . There are a few studies, for a select group of infants, which have demonstrated that infants can be managed safely in an outpatient setting without increasing treatment time . Benefits of home-based detoxification include: decreasing length of hospital stay and associated health care costs, promoting infant–caretaker attachment and increasing breastfeeding rates . Of course, these benefits must be weighed against possible risks. Before discharge, the infant should be demonstrating tolerance of pharmacological tapering, with consistent withdrawal scores < 8. Also, a clear, documented medications weaning plan should be in place for the HCP and family to follow. Other community referrals to consider may include ongoing maternal substance abuse treatment programs, public health and child and youth services, a community support worker, infant development programs and/or parenting support groups. Also, the families and/or guardians must show they can provide a supportive and safe home environment .
Opioid-dependent mothers should be informed that their infant, who has been exposed to natural, semi-synthetic or synthetic opioids during pregnancy, will require observation for symptoms and signs of neonatal withdrawal following birth. Antenatal consultation by perinatology, paediatrics and/or neonatology is encouraged.
All infants at risk for developing neonatal opioid withdrawal should be evaluated using a reliable, valid neonatal withdrawal score instrument.
Information and guidelines for HCPs on managing infants born to opioid-dependent mothers should outline the continuum of care. Strategies to support keeping mothers and infants together and breastfeeding are essential. Providing nonpharmacological interventions, such as skin-to-skin contact, developmental positioning, comfort measures, minimizing environmental stimuli, ensuring adequate nutrition and providing pharmacological treatment when indicated, are key components of a comprehensive plan.
An effective and well-coordinated discharge plan that involves an interprofessional health care team and outlines a comprehensive medications weaning schedule, is essential to ensure seamless transition from hospital to community, and for maintaining continuity of care.
This practice point was reviewed by the Community Paediatrics, Drug Therapy and Hazardous Substances and First Nations, Inuit and Métis Health Committees of the Canadian Paediatric Society. It has also been reviewed by representatives from the Society of Obstetricians and Gynaecologists of Canada.
CPS FETUS AND NEWBORN COMMITTEE
Members: Mireille Guillot MD, Leonora Hendson MD, Ann Jefferies MD (past Chair), Thierry Lacaze-Masmonteil MD (Chair), Brigitte Lemyre MD, Michael Narvey MD, Leigh Anne Newhook MD (Board Representative), Vibhuti Shah MD
Liaisons: Radha Chari MD, The Society of Obstetricians and Gynaecologists of Canada; James Cummings MD, Committee on Fetus and Newborn, American Academy of Pediatrics; William Ehman MD, College of Family Physicians of Canada; Roxanne Laforge RN, Canadian Perinatal Programs Coalition; Chantal Nelson PhD, Public Health Agency of Canada; Eugene H Ng MD, CPS Neonatal-Perinatal Medicine Section; Doris Sawatzky-Dickson RN, Canadian Association of Neonatal Nurses
Principal authors: Thierry Lacaze-Masmonteil MD, Pat O’Flaherty MEd, MN, RN-EC
- Turner SD, Gomes T, Camacho X et al. Neonatal opioid withdrawal and antenatal opioid prescribing. CMAJ Open Research 2015;3(1):E55-61.
- Dow K, Ordean A, Murphy-Oikonen J et al.; Neonatal Abstinence Syndrome Work Group. Neonatal abstinence syndrome clinical practice guidelines for Ontario. J Popul Ther Clin Pharmacol 2012;19(3):e488–506.
- Patrick SW, Schumacher RE, Benneyworth BD, Krans EE, McAllister JM, Davis MM. Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009. JAMA 2012;307(18):1934–40.
- Vucinovic M, Roje D, Vucinovic Z, Capkun V, Bucat M, Banovic I. Maternal and neonatal effects of substance abuse during pregnancy: Our ten-year experience. Yonsei Med J 2008;49(5):705–13.
- Opiate Addiction and Treatment Resource. www.opiateaddictionresource.com/opiates/types_of_opioids (Accessed August 22, 2017).
- Finnegan LP. Substance Abuse in Canada: Licit and Illicit Drug Use During Pregnancy; Maternal, Neonatal and Early Childhood Consequences. Ottawa, Ont.: Canadian Centre on Substance Abuse, 2013: www.ccsa.ca/Resource%20Library/CCSA-Drug-Use-during-Pregnancy-Report-2013-en.pdf (Accessed August 3, 2017).
- Logan BA, Brown MS, Hayes MJ. Neonatal abstinence syndrome: Treatment and pediatric outcomes. Clin Obstet Gynecol 2013;56(1):186–92.
- Behnke M, Smith VC; Committee on Substance Abuse; Committee on Fetus and Newborn. Prenatal substance abuse: Short- and long-term effects on the exposed fetus. Pediatrics 2013;131(3):e1009–24.
- WHO. Guidelines for the Identification and Management of Substance Use and Substance Use Disorders in Pregnancy. Geneva, Switzerland: WHO, 2014. http://apps.who.int/iris/bitstream/10665/107130/1/9789241548731_eng.pdf (Accessed August 3, 2017).
- Wong S, Ordean A, Kahan M; Maternal Fetal Medicine Committee; Family Physicians Advisory Committee; Medico-legal Committee; Ad hoc Reviewers; Special Contributors. Substance use in pregnancy. J Obstet Gynaecol Can 2011;33(4):367–84. www.researchgate.net/publication/51059321_Substance_use_in_pregnancy (Accessed August 3, 2017).
- Jones HE, Finnegan LP, Kaltenbach K. Methadone and buprenorphine for the management of opioid dependence in pregnancy. Drugs 2012;72(6):747–57.
- Ordean A, Kahan M, Graves L, Abrahams R , Boyajian T. Integrated care for pregnant women on methadone maintenance treatment: Canadian primary care cohort study. Can Fam Physician 2013;59(10):e462–9.
- Burns L, Mattick RP, Lim K, Wallace C. Methadone in pregnancy: Treatment retention and neonatal outcomes. Addiction 2007;102(2):264–70.
- Casper T, Arbour M. Evidence-based nurse-driven interventions for the care of newborns with neonatal abstinence syndrome. Adv Neonatal Care 2014;14(6):376–80.
- Ordean A, Chisamore BC. Clinical presentation and management of neonatal abstinence syndrome: An update. Res Rep Neonatol 2014;4:75–86. www.dovepress.com/clinical-presentation-and-management-of-neonatal-abstinence-syndrome-a-peer-reviewed-full-text-article-RRN (Accessed August 3, 2017).
- Kocherlakota P. Neonatal abstinence syndrome. Pediatrics 2014;134(2):e547–61.
- Coyle MG, Ferguson A, Lagasse L, Oh W, Lester B. Diluted tincture of opium (DTO) and phenobarbital versus DTO alone for neonatal opiate withdrawal in term infants. J Pediatr 2002;140(5):561–4.
- Ruwanpathirana R , Abdel-Latif ME, Burns L, et al. Prematurity reduces the severity and need for treatment of neonatal abstinence syndrome. Acta Paediatr 2015;104(5):e188–94.
- Hudak ML, Tan RC; Committee on Drugs; Committee on Fetus and Newborn; American Academy of Pediatrics. Neonatal drug withdrawal. Pediatrics 2012;129(2):e540–60.
- Newnam KM. The right tool at the right time: Examining the evidence surrounding measurement of neonatal abstinence syndrome. Adv Neonatal Care 2014;14(3):181–6.
- Finnegan LP, Kron RE, Connaughton JF, Emich JP. Assessment and treatment of abstinence in the infant of the drug-dependent mother. Int J Clin Pharmacol Biopharm 1975;12(1–2):19–32.
- Asti L, Magers JS, Keels E, Wispe J, McClead RE. A quality improvement project to reduce length of stay for neonatal abstinence syndrome. Pediatrics 2015;135(6):e1494–500.
- D’Apolito K, Finnegan LP. Assessing Signs and Symptoms of Neonatal Abstinence Using the Finnegan Scoring Tool: An Inter-observer Reliability Program. 2nd ed. Nashville, TN: NeoAdvances, 2010.
- Pulatie K. The legality of drug-testing procedures for pregnant women. Virtual Mentor 2008;10(1):41–4.
- Levy S, Siqueira LM, Ammerman SD et al.; Committee on Substance Abuse. Testing for drugs of abuse in children and adolescents. Pediatrics 2014;133(6):e1798–1807.
- Gibbs J, Newson T, Williams J, Davidson DC. Naloxone hazard in infant of opioid abuser. Lancet 1989;2(8655):159–60.
- McKnight S, Coo H, Davies G et al. Rooming-in for infants at risk of neonatal abstinence syndrome. Am J Perinatol 2016;33(5):495–501.
- MacMillan KDL, Rendon CP, Verma K, Riblet N, Washer DB, Volpe Holmes A. Association of rooming-in with outcomes for neonatal abstinence syndrome: a systematic review and meta-analysis. JAMA Pediatr 2018 [Epub ahead of print]. doi: 10.1001/jamapediatrics.2017.5195.
- Holmes AV, Atwood EC, Whalen B, et al. Rooming-in to treat neonatal abstinence syndrome: Improved family-centered care at lower cost. Pediatrics 2016;137(6):e20152929.
- Hodgson ZG, Abrahams RR. A rooming-in program to mitigate the need to treat for opiate withdrawal in the newborn. J Obstet Gynaecol Can 2012;34(5):475–81.
- Jansson LM, Velez M, Harrow C. The opioid-exposed newborn: Assessment and pharmacologic management. J Opioid Manag 2009;5(1):47–55.
- Abdel-Latif ME, Pinner J, Clews S, Cooke F, Lui K, Oei J. Effects of breast milk on the severity and outcome of neonatal abstinence syndrome among infants of drug-dependent mothers. Pediatrics 2006;117(6):e1163–9.
- Wachman EM, Byun J, Philipp BL. Breastfeeding rates among mothers of infants with neonatal abstinence syndrome. Breastfeed Med 2010;5(4):159–64.
- Maguire DJ, Rowe MA, Spring H, Elliott AF. Patterns of disruptive feeding behaviors in infants with neonatal abstinence syndrome. Adv Neonatal Care 2015;15(6):429–39; quiz E1–2.
- LaGasse LL, Messinger D, Lester BM, et al. Prenatal drug exposure and maternal and infant feeding behaviour. Arch Dis Child Fetal Neonatal Ed 2003;88(5):F391–9.
- Murphy-Oikonen J, Brownlee K, Montelpare W, Gerlach K. The experiences of NICU nurses in caring for infants with neonatal abstinence syndrome. Neonatal Netw 2010;29(5):307–13.
- MacMullen NJ, Dulski LA, Blobaum P. Evidence-based interventions for neonatal abstinence syndrome. Pediatr Nurs 2014;40(4):165–72, 203.
- Bagley SM, Wachman EM, Holland E, Brogly SB. Review of the assessment and management of neonatal abstinence syndrome. Addict Sci Clin Pract 2014;9(1):19
- Kraft WK, Adeniyi-Jones SC, Chervoneva I et al. Buprenorphine for the treatment of the neonatal abstinence syndrome. N Engl J Med 2017;376(24):2341–8.
- Kraft WK, Stover MW, Davis JM. Neonatal abstinence syndrome: Pharmacologic strategies for the mother and infant. Semin Perinatol 2016;40(3):203–12.
- Streetz VN, Gildon BL, Thompson DF. Role of clonidine in neonatal abstinence syndrome: A systematic review. Ann Pharmacother 2016;50(4):301–10.
- Smirk CL, Bowman E, Doyle LW, Kamlin CO. How long should infants at risk of drug withdrawal be monitored after birth? J Paediatr Child Health 2014;50(5):352–5.
- Provincial Council for Maternal and Child Health. Neonatal Abstinence Syndrome (NAS) Clinical Practice Guidelines. July 19, 2011 (revised March 30, 2012): https://pqcnc-documents.s3.amazonaws.com/nas/nasresources/NASGuidelines.pdf (Accessed August 3, 2017).
- Smirk CL, Bowman E, Doyle LW, Kamlin O. Home-based detoxification for neonatal abstinence syndrome reduces length of hospital admission without prolonging treatment. Acta Paediatr 2014;103(6):601–4.
- McQueen K, Murphy-Oikonen J. Neonatal abstinence syndrome. N Engl J Med 2016;375(25):2468–79.
- Backes CH, Backes CR , Gardner D, Nankervis CA, Giannone PJ, Cordero L. Neonatal abstinence syndrome: Transitioning methadone-treated infants from an inpatient to an outpatient setting. J Perinatol 2012;32(6):425–30.
- Marcellus L, Loutit T, Cross S. A national survey of the nursing care of infants with prenatal substance exposure in Canadian NICUs. Adv Neonatal Care 2015;15(5):336–44.
- Johnston A, Metayer J, Robinson E. Management of Neonatal Opioid Withdrawal. Section 4 of Treatment of Opioid Dependence in Pregnancy: Vermont Guidelines. Vermont Children’s Hospital at Fletcher Allen Health Care, 2010. http://contentmanager.med.uvm.edu/docs/default-source/vchip-documents/vchip_5neonatal_guidelines.pdf ?sfvrsn=2 (Accessed August 3, 2017).
Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.