1. Please describe the different opioid receptors' functions.
2. Heroin is ultimately metabolized to morphine. What specific test would you need to identify heroin?
3. What are the 3 FDA-approved medications to treat opioid use disorder? What the mechanisms of action for the 3 medications? (agonist, partial agonist, antagonist, etc.)
4. If you have a patient who ishighly motivated for abstinence, which of the 3 medications would you choose?
5. If you have a patient with a history ofseveral overdoses after attempting several detoxes,which of the 3 medications might you consider and why?
Please read the articles related to perinatal substance use.
6. What is your "gut" response to treating a pregnant woman using substances?Do you agree with use of methadone or buprenorphine maintenance for a pregnant woman using opioids? Why or why not?
Editorial V O L U M E 1 0 I S S U E 1 2 0 1 4 9infant A U D I T A N D S U R V E Y© 2014 SNL All rights reserved Substance misuse within the UKpopulation continues to be a major public health concern (FIGURE 1)1. Approximately one in four of those entering drug treatment programmes in 2010-2011 were female, many of who were of childbearing age. Pregnant substance misusing women need supportive and coordinated care during pregnancy. They have been highlighted as a specific group in need by the National Institute for Health and Care Excellence (NICE) in their guidance on the management of pregnant women with complex social factors2. Locally in Leeds, between 50 and 80 pregnant drug users book for antenatal care at the Leeds Addiction Unit (LAU) every year. The numbers have remained relatively static over a five-year period (FIGURE 2). The vast majority of these women are receiving prescribed opioid maintenance therapy (ie methadone or buprenorphine) with many using additional illicit substances. Infants born to substance misusing mothers are at a higher risk of poor pregnancy outcomes including prematurity, intrauterine growth restriction and stillbirth3,4. NAS: the effect of maternal substance misuse on the newborn infant The sudden cessation at birth of a continuous supply of an addictive substance (most often an opioid) via the Neonatal abstinence syndrome: the role of breastfeeding Treatment for neonatal abstinence syndrome (NAS) can be prolonged, in some cases necessitating a lengthy hospital stay. There is increasing evidence that breastfeeding affected infants can be beneficial in reducing the severity and intensity of symptoms of NAS. Substance misusing mothers are a vulnerable group with low breastfeeding rates. Support and a positive attitude from healthcare professionals are essential in helping these women to breastfeed their infants. This review, based on current literature and local experience from a tertiary care unit, evaluates breastfeeding in infants susceptible to NAS and suggests strategies to promote breastfeeding among this group of women. Munisha Balain MBBS, MRCPCH Specialty Registrar, Embrace, Yorkshire and Humber Infant and Children’s Transport Service, Barnsley [email protected] Kathryn Johnson MBChB, FRCPCH Consultant Neonatologist, Neonatal Unit, Leeds General Infirmary Keywords substance misuse in pregnancy; neonatal abstinence syndrome; breastfeeding Key points Balain M., Johnson K. Neonatal abstinence syndrome: the role of breastfeeding. Infant 2014; 10(1): 9-13. 1. Neonatal abstinence syndrome (NAS) is a common problem on postnatal wards and neonatal units 2. Breastfeeding reduces the severity and intensity of symptoms of NAS thus reducing the need for treatment and the length of hospital stay. 3. Information provision and education of healthcare professionals about the benefits of breastfeeding in NAS may help to improve breastfeeding rates and reduce the burden of disease. placenta can lead to the development of NAS in the days after birth. NAS is characterised by a variety of symptoms, which are unpleasant for the infant and can be difficult to treat. The common clinical features of NAS are detailed in TABLE 1. Up to 80% of drug-exposed infants develop NAS5 with many requiring pharmacological treatment, often necessitating a prolonged stay within the neonatal service6. Over the last decade, evidence from the literature consistently supports the use of morphine as the treatment of choice in infants where pharmacological treatment is necessary5,7,8. In addition to opiate treatment, non- pharmacological supportive care of these infants is vital. A recent report from the American Academy of Paediatrics highlights the need for non-pharma- cological supportive measures, eg minimising environmental stimuli9; simple techniques such as nursing in a quiet room with dim lighting may offer significant benefit10. Evidence in support of breast- feeding in the management of NAS Breastfeeding rates in mothers whose infants are at risk of NAS are lower than that of the general population11. There is evidence however, that breastfeeding may be a strategy that can be used to manage, treat or even prevent NAS. A U D I T A N D S U R V E Y 10 V O L U M E 1 0 I S S U E 1 2 0 1 4 infant In order to study the link between breastfeeding and NAS, a literature review was conducted with the following PICO question12: In infants born to drug-dependent mothers (Patient), does breastfeeding (Intervention), as compared to formula feeding (Comparison), lead to reduced NAS symptoms (Outcome)? Seven relevant studies were found, the results of which are summarised in TABLE 2. In summary, the studies consistently show that breastfed infants born to substance misusing mothers have significantly less symptoms of NAS, need less treatment for NAS and have a shorter duration of hospital stay compared to formula fed infants. These effects are seen regardless of the length of gestation and the type of drug exposure. However, there are a number of limitations to these studies: 1. The studies are often difficult to conduct due to the inherent nature of the topic studied – most instances rely on self- disclosure as a means of identifying drug use. 2. Feeds are often mixed (ie both formula and breast milk) leading to difficulty in analysis of results. 3. The breastfed and formula fed groups are self-selected and it is difficult to methadone excreted in breast milk. These studies have unequivocally concluded that only low levels of methadone are excreted into breast milk (TABLE 3). Many authors have suggested that the levels of methadone transmitted in human milk are below the threshold of physiological significance. The question is, are there other factors, instead of or in addition to, passive transference of opioids in breast milk that lead to the mitigating effects of breastfeeding in NAS? Supportive care measures such as soothing, swaddling and frequent feeding are known to alleviate the symptoms of NAS. It has been shown that caring for infants with NAS on the postnatal ward with their mothers rather than on the neonatal unit reduces the need for treatment and duration of hospital stay, even when breastfeeding is not a factor26. Breastfeeding is associated with an increased one-to-one time and interaction between mother and infant. Therefore some beneficial effects of breastfeeding could be related to the positive effects of mother-child bonding and one-to-one care of the withdrawing infant, rather than the components of breast milk27. However, the comforting effects of the act of breastfeeding do not entirely explain the differences between breast and formula fed infants in NAS. The benefits of breast milk have also been seen in infants who are fed maternal breast milk by gavage tubes, without the comfort of sucking13. These benefits are also seen when expressed breast milk is given to premature infants with NAS13. In addition, rebound withdrawal symptoms requiring pharmacological treatment following abrupt cessation of breastfeeding have also been described28 and this finding is match groups and establish stringent controls. 4. In many of the studies, the mothers in the formula fed cohort were younger, more likely to be unemployed, had less antenatal visits, comprised more polydrug users and belonged to a more socially disadvantaged group13. 5. Conversely, breastfeeding mothers were more likely to have comprehensive antenatal care, less likely to admit to polydrug use and were less likely to be notified as an at-risk parent to the child welfare services. 6. Formula fed infants are generally from higher risk groups, possibly confounding the results. Despite the limitations, the strength of the evidence appears in favour of a positive effect of breastfeeding in infants with NAS. Why do breastfed infants have fewer symptoms than formula fed infants? One logical explanation is that opioids are excreted in breast milk, leading to an infant’s continued exposure to the drug and hence less withdrawal symptoms. There have been a number of studies, particularly in relation to methadone, aiming to quantify the amount of FIGURE 1 Age and gender of UK drug users registered for treatment in 2010-111. Female Male 18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60+ Age 5,000 10,000 15,000 20,000 25,000 30,000 35,000 N u m b er o f re gi st er ed d ru g u se rs Respiratory Neurological Gastrointestinal dysfunction Autonomic signs Tachypnoea Tremors Irritability Hypertonicity Seizures Poor feeding Poor weight gain Vomiting Diarrhoea Sweating Nasal stuffiness Fever Mottling TABLE 1 Common clinical features of neonatal abstinence syndrome. FIGURE 2 Number of drug-using women booking at Leeds Addiction Unit antenatal clinic. 70 80 60 50 40 30 20 10 0 N u m b er o f p at ie n ts 2007 2008 2009 2010 2011 Year A U D I T A N D S U R V E Y V O L U M E 1 0 I S S U E 1 2 0 1 4 11infant supported by the clinical experience of the authors. How the various factors contribute to the alleviation of withdrawal symptoms in NAS is not yet fully understood. Nevertheless, breastfeeding does have positive effects and as a result, it should be strongly promoted. Challenges to breastfeeding in the substance misusing population The baseline rates of breastfeeding of substance misusing women are lower than the general population11 and there are a number of challenges to breastfeeding in this group of women. This is multifactorial, reflecting a combination of: ■ lack of information ■ negative attitudes towards breastfeeding ■ an unsupportive social environment ■ low motivation to start and continue breastfeeding. There is a lack of information regarding the additional positive benefits of breastfeeding with regards to NAS in infants of substance misusing mothers. A review of eight breastfeeding-related leaflets and information provided by national agencies and on reputable websites provides no information on the potential additional benefits of breast- feeding in this group of women29-36. There is even an active suggestion to not breastfeed36. The authors could not find any dedicated information source regarding breastfeeding in relation to NAS (outside of medical literature) that would be readily available to the general population. In Leeds, before commencement of the promotion of breastfeeding for substance misusing mothers, a survey was conducted to ascertain the attitudes of healthcare professionals towards feeding infants at risk of NAS. The thirty medical and nursing staff surveyed revealed negative attitudes towards recommending and promoting breastfeeding in this group of women. Thirteen per cent of those surveyed felt breastfeeding should not be encouraged in drug-using mothers and 11% believed that breastfeeding is harmful for infants if their mothers are drug users. Only 23% of respondents strongly agreed that breastfeeding should be promoted for these infants. Hence lack of information about the benefits of breastfeeding and lack of supportive attitudes among healthcare professionals are major contributing factors to low breastfeeding rates in substance misusing mothers. HIV is the only medical contraindication to breastfeeding in substance misusing mothers.