By: Nicole Stevens

 A syndrome of drug withdrawal with non- specific signs and symptoms that may occur in babies following in-utero drug exposure.  Exposure may be to opiates, stimulants, sedatives, alcohol and/or some antidepressants.  It is not possible to predict, before birth, which babies may develop NAS.  The incidence of NAS is not directly related to the type or amount of substance used.  NAS is readily diagnosed and treated.

In-utero fetal exposure to the following major classes of drugs may lead to neonatal withdrawal:  Opioids (methadone, heroin, buprenorphine)  CNS stimulants (amphetamines, cocaine, SSRI’s, SNRI’s)  CNS depressants (alcohol, barbiturates, benzodiazepines)  Hallucinogens including inhalents (glues, paint thinner, petrol)

 An Australian survey reported illicit drug use in 6% of women who were pregnant and or breastfeeding in the preceding 12 months  The IDEAL study in the USA reported 10.7% of mothers had used illicit drugs during pregnancy  Alcohol use in Australia was reported in almost half of pregnant women and women who were breastfeeding up to 6 months postpartum; in the USA, 4.5% of pregnant women reported binge drinking in the past month.

 A detailed antenatal history of maternal drug use and psychosocial assessment will help to identify those babies at risk of NAS  Consider antenatal paediatric consult to discuss implications for baby after birth (eg. minimum length of stay, monitoring, potential admission to SCN, potential medication)  Consider tour of SCN facility

Antenatal care should include (if applicable):  Enrolment in an opioid treatment program  Education regarding the safety of opioid replacements in pregnancy and lactation  Drug use relapse prevention and supportive counselling  QUIT tobacco program  Antenatal CPU notification if significant concerns.  Screening for blood borne viruses, and rescreening at 36 wks if high risk

 The usual methadone/buprenorphine dose will not provide any analgesia during labour  Opioids, including pethidine, will be less effective; regional anaesthesia may be more appropriate  Reassurance to woman that all routine pain relief will be offered  Specialist consultation may be required for post-partum pain management (eg. Post caesarean section).

 Do not administer naloxone to babies of known or suspected opioid dependent women during resuscitation or in the newborn period.  Naloxone is not part of the ARC guidelines anymore, and should only be given following a medical directive/order.  Naloxone, given to infants of mothers who are opioid dependent, can cause a sudden/acute withdrawal with possible seizures.

Neonatal factors that are known to be associated with maternal drug use include:  Low birth weight  Intrauterine growth restriction  Unexplained prematurity

Onset of withdrawal symptoms varies and is dependent on the:  Dose; half life and timing of last drug dose prior to birth. Exposure to some substances (eg. Cocaine, alcohol) close to time of birth may result in signs of neonatal intoxication. Withdrawal from heroin may be apparent in 24 hours. From methodone/buprenorphine may be delayed up to 3 – 7 days or longer. Variable onset for SSRI/SNRI’s (usually 2 – 7 days)

Depends on many factors:  Maternal dose  Class of drug  Time of most recent use  Unknown factors which influence maternal and infant metabolism  Impact of neonatal immaturity or illness  Poly drug use may further complicate the clinical presentation

Central nervous system:  Tremors  Irritability  Increased wakefulness  High pitched crying  Increased muscle tone  Hyperactive deep tendon reflexes  Exaggerated moro reflex  Seizures  Frequent yawning and sneezing

Gastrointestinal:  Poor feeding  Uncoordinated and constant sucking  Vomiting  Diarrhoea  Dehydration  Poor weight gain

Autonomic:  Increased sweating  Nasal stuffiness  Fever  Mottling  Temperature instability

If signs of withdrawal are displayed:  Consider presence of concurrent illness (differential diagnosis may be: infection, hypoglycaemia, hypocalcaemia or metabolic disorders)  Review risk factors for neonatal sepsis  Investigate to exclude infection, metabolic disturbances  Treat concurrent illness  Review maternal history for licit/illicit substance use  Discuss possible undisclosed substance use with mother.

Validated assessment tools include:  Finnegan  Modified Finnegan Neonatal Abstinence Severity Score  Lipsitz tool  Neonatal Withdrawal Inventory Finnegan or Modified Finnegan is accepted as an appropriated form of assessment in Australia.

All babies born to drug dependent mothers should receive:  Routine postnatal ward monitoring  Specific assessment with the Finnegan or Modified Finnegan score: commence this 2 hours after birth and continue 4 hourly thereafter.  The Finnegan scoring system is dynamic, assessment is not at a single time point, scores should reflect all the symptoms observed between scoring times

Suspect NAS if infant:  Is unsettled  Is irritable  Has a high pitched cry  Has tremors/jitteriness  Does not feed well and/or has diarrhoea If a baby is transferred to SCN for clinical assessment following the onset of symptoms he/she may be returned to the PNW following an appropriate period of observation if he/she does not require medication

 If infants commence pharmocological treatment monitoring will be required with the minimum of an apnoea monitor, consider use of cardiorespiratory monitor if the infant is requiring high doses of morphine and/or phenobarbitone, is premature or has a concurrent illness.

 May have less severe symptoms of withdrawal from opioid exposure  The onset is likely to be later  Symptoms may be confused with other manifestations of prematurity (eg. Respiratory distress, poor feeding); loose stools, sneezing and yawning are symptoms to consider to be of importance in the preterm infant.  Depending on gestation scoring may not be considered to be appropriate or necessary.

 Non-pharmacological: swaddling, cuddling, use of dummies, quiet environment, reduced stimulation, generous feeding.  Pharmacological: oral morphine; oral phenobarbitone.  Breastfeeding not contraindicated, except if the mother is HIV positive, hep C positive with damaged/bleeding nipples or using heroin, cocaine or amphetamines (doses unpredictable, unsafe for neonate – and mother!)

 If being managed on postnatal ward and behaviour is worsening and scores increasing, consider admission to SCN for closer observation prior to commencing treatment  If scores are greater than or equal to 12 for 2 consecutive scores, or greater than or equal to an average of 8 for 3 consecutive scores treatment is indicated.  If maternal dependence is an opioid commence morphine, if a non-opioid commence phenobarbitone.

 Usually commence treatment at 500mcg/kg 6/24. If symptoms not controlled, increase dosing interval to 4/24, if still not controlled can go up to 750mcg/kg – 1000mcg/kg (depending on local guidelines)  Symptoms persisting despite this dosing – consider adding phenobarbitone  Dose reduction is done when scores are consistently < 8 for 48 – 72 hours; dose is reduced by 10% of the original dose.

 May be required if morphine therapy is optimised and still not controlling symptoms  Drug of choice for non-opioid dependence  Commonly used in situations of poly drug use  A longer term therapy, and babies are commonly discharged home on it.  Give loading dose for rapid onset; continue with maintenance dose; increase dose to control NAS if required

 Diagnosis is based on a set of criteria comprised of abnormalities in 3 main categories: growth retardation, characteristic facial features, and CNS anomalies (including intellectual impairment). The intellectual impairment associated with FAS is permanent.  Literature supports the plausibility of alcohol as a teratogen and a number of potential mechanisms have been described.  The impact of heavy consumption will depend on the timing  First 8 weeks: Primary teratogenic effects  Later exposure: may affect growth and behavioural and cognitive disorders.

Physical characteristics:  Small eye openings  Microcephaly (small head and brain)  Flat upper lip  Flattened philtrum  Flat midface  Growth restriction  Impaired coordination  Neurosensory hearing loss  Developmental delays

Neonates exposed to these substances may present with complications of:  Poor feeding (possibly requiring NGT insertion/admission to SCN)  Developmental delays Neonates exposed to ‘uppers’ inutero are waiting for the fix to bring them up after they are born, hence why they can have reduced activity and be delayed in the essential behaviour of establishing suck feeds.

 Dangerous and unpredictable, strength/quality can vary from hit to hit  Neonates exposed in utero, will often display early signs of withdrawal (1-2 days). Heroin is a ‘downer’ so babies can display very irritable, unsettled behaviour – excessive crying, increased muscle tone, jittery, poor feeding, feed intolerance and can appear to be in pain; asking a mother what going cold turkey feels like, may help to explain the symptoms a baby is exhibiting,

 Prescription medications, traditionally used in controlled withdrawal programs for ceasing use of heroin. Safer because of the controlled dosing, taken orally.  Neonates exposed in-utero may not show signs of withdrawal for 7 – 14 days after birth  Anecdotally, does not appear to be dose dependent.  Treatment for severe withdrawal is oral morphine

 Quiet environment  Low stimulus (minimise noise, eye contact)  Swaddle (in a light wrap, eg. muslim)  Often run ‘hot’ so require minimal clothing and blankets  Observe and record scores 4/24  Report escalating scores if treatment appears inadequate

 Involve the multidisciplinary team (social work, M&CHN, paediatrician, GP and other appropriate community supports)  Not all cases of maternal drug use will require notification to child protection  In the cases of illicit drug use child protection should be notified.

 Excessive weight loss (greater than 10%)  Baby less than a week of age  Suspected neglect or abuse  Suspected domestic violence  A court order preventing baby from being discharged home  Requirement for further assessment of withdrawal  Commencement of pharmacological therapy

May be considered from some units if:  If multidisciplinary team agrees that this is a safe option  Baby is term and healthy  Sucking all feeds and gaining weight  Stable on medication and tolerating dose reductions  Parents are able to administer medication  Appropriate education for parents has been attended to and supports are in place.

 The Womens Drug and Alcohol service   National clinical guidelines for the management of drug use during pregnancy birth and the early development years of the newborn. Commissioned by the Ministerial Council on Drug Strategy  Australian Institute of Health and Welfare. Statistics on drug use in Australia. Canberra: 2004  Arria AM, Derauf C, Lagasse LL, Grant P, Shah R, Smith L, et al. Methamphetamine and other substance use during pregnancy: preliminary estimates from the Infant Development, Environment, and Lifestyle (IDEAL) study. Maternal Child Health J. 2006; 10(3):  Substance Abuse and Mental Health Services Administration. (2009). Results from the 2008 National Survey on Drug Use and Health: National Findings. (Office of Applied Studies, NSDUH Series H-36, HHS Publication No. SMA ) Rockville, MD.