Improving Care for Opioid Exposed Newborns September 11, 2006 NNEPQIN Dartmouth Hitchcock Medical Center Anne Johnston, MD Associate Professor of Pediatrics University of Vermont

Objectives Signs and symptoms of opioid exposure in newborns Management of opioid-exposed newborns Follow-up of the opioid-exposed infant Vermont outcomes MOTHER study

Neonatal Abstinence Syndrome A generalized disorder presenting as CNS irritability, GI dysfunction, autonomic symptoms Usually due to withdrawal from opioids (in-utero or postnatal exposure) Maternal SSRI implicated in neonatal abstinence syndrome 50-75% of infants born to mothers on opioids will need treatment Infants born to mothers on methadone will often have a delay in the onset of symptoms and may have more severe and prolonged symptoms Severity of symptoms has not been shown to correlate with methadone dose

Opioid Withdrawal Symptoms

Management of Neonatal Abstinence Syndrome Supportive treatment Detailed maternal history including drug intake, methadone dose, alcohol intake, tobacco use Consider urine +/- meconium toxicology screens Establish plans re: breast feeding Consult to Social Services Consider referral to DCF Contact infant’s primary care provider

Management of Neonatal Abstinence Syndrome Admit to NBN, scores q 3-4h (Modified Finnegan) Avoid overstimulation If score  9, then repeat score after feeding, if scores ≥ 9, consider pharmacologic treatment Consider other causes of symptoms (metabolic, sepsis, etc)

NAS: Pharmacologic Treatment Phenobarbital  most useful for polydrug use; limited use for opioid withdrawal Dilute tincture of opium  used for opioid withdrawal, short half life Paregoric  not recommended for neonates: high EtoH, camphor is a CNS stimulant, benzoic acid may compete for bilirubin binding Morphine  used for opioid withdrawal, short half life, respiratory depression Methadone  used for opioid withdrawal; long half life, well tolerated, may be a prolonged wean period

NAS: Methadone Initial dose of 0.5 mg (0.3 – 0.7 mg) po Q12 hours Give additional doses if necessary at 6-36 hours; may also give rescue morphine; do not increase the baseline dose within the first 2 days If infant is somnolent, stop methadone and wait until mild signs of withdrawal, then restart at a reduced dose (every 12 hours off, decrease by 0.05 mg) Breast feeding is encouraged depending upon infant’s treatment plan, providing the mother is HIV negative

NAS: Morphine Sulfate Morphine sulfate 0.4 mg/ml solution Initial dose based upon symptoms, not score Initial doses:  Score 9 – 12:0.04 mg (0.1 ml)  Score 13 – 16:0.08 mg(0.2 ml)  Score 17 – 20:0.12 mg(0.3 ml)  Score 21 – 24:0.16 mg(0.4 ml)  Score > 24:0.2 mg(0.5 ml) Adjust dose thereafter based upon symptoms Start weaning after stable scores < 9 for 48 hours Wean every 24 hours by 0.02 mg

The Special Needs of Parents Most feel uncomfortable in the NICU setting Increased stigma with “drug exposed” infant Acknowledge health care providers’ feelings/prejudices Critical time to establish relationship with mother Remove barriers to family involvement Factually acknowledge mothers actions and resultant fetal effects

NAS: Discharge Planning Parent / caregiver education regarding symptoms of withdrawal Methadone prescription filled for 14 days of methadone for infant VNA/Home Health visits scheduled Primary Care Provider appointment scheduled Neonatal Medical Follow-Up appointment scheduled Maternal substance abuse treatment plan confirmed

NAS: Outpatient Treatment Wean methadone q 3-4 days by 5- 10% from discharge dose as tolerated Follow weights and parental history Do not discontinue breast feeding abruptly without discussion Q weekly visits MD, alternate Neonatal Medical Follow-Up Clinic with Primary MD Discontinue methadone when dose is less than 0.05 mg/day

Management of Neonatal Abstinence Syndrome: Outcomes Confounded by other variables During 1st year: increased incidence of sleep disturbances and feeding difficulties Developmental delay may be increased, however there are no convincing data to support this Elevated incidence of attention deficit disorder and behavioral problems Strauss et al Kaltenbach et al. 1989

Buprenorphine and NAS Published literature: at least 309 infants born to women on buprenorphine 191 of these infants showed signs of NAS, with 50% of these receiving treatment – 31% (confounding variables – other drug use) However – no prospective, randomized controlled trials Selected studies:  Johnson et al. Use of buprenorphine in pregnancy: Patient management and effects on the neonate. Drug and Alchohol Dependence 79:S87-S101, 2003a  Marquet et al. Buprenorphine withdrawal syndrome in a newborn. Clinical Pharmacology and Therapeutics 62(5): , 1997  Schindler at al. Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy. Addiction 98: , 2003  Fischer et al. Buprenorphine maintenance in pregnant opiate addicts. European Addiction Research 4(Supp):32-26, 1998

Buprenorphine and Breastfeeding Buprenorphine passes into breast milk at a plasma to milk ratio of 1:1 Poor oral bioavailability of buprenorphine Therefore infant will be exposed to 1/5 – 1/10 of the total buprenorphine available Literature on 40 – 50 women  NAS not suppressed nor were signs seen following cessation of breastfeeding

Vermont Experience: Infants born to opioid dependent women on methadone or buprenorphine maintenance

Vermont Experience August 2000 – September 31, 2005  146 infants born to women with opioid addiction on methadone, buprenorphine  21 infants born to women on prescribed opiates (no history of substance abuse)  35 infants with post-natal opioid exposure and dependence (discharged on opioids)

Vermont Experience Average age: 25.4 years County  Chittenden: 52%  Washington: 19%  Rutland: 10%  Orleans: 3%  Caledonia: 3%  Windham:1%  Addison:1%  Franklin:1%  Grand Isle:0.5%  Lamoille:0.5% Other children:67% Other children in “custody”:47%

Mean presentation: 19 wks Hepatitis B surface antigen positive: 3% Hepatitis C Antibody Positive: 39% HIV positive: 0% Vermont Experience: Maternal Characteristics

Opioid-Dependent Pregnancies Timing of Presentation Fiscal Years % Presentation < 24 weeksMean Gestational Age at Presentation

Opioid-Dependent Pregnancies on Treatment Delivery < 37 Weeks Gestation Fiscal Years

Opioid-Dependent Pregnancies on Treatment Mean Birth Weights Fiscal Years

Infants requiring pharmacologic treatment at discharge  61% Length of treatment  1–11 months (median 5.1 months) Deaths: 2 infants  possible SIDS  accidental suffocation – co-sleeping Vermont Experience: Infant Outcomes

Breast feeding  51/100 (51%) discharged on breast milk Living situation  81/100 (81%) discharged in the care of the mother  59/83 (71%) living with their mother at 1 year of age Developmental Assessment  8-10 mos. of age  Completed on 70 infants to date  64 within normal limits on all parameters  6 infants had mild abnormalities including gross motor delay, global developmental delay

Vermont Experience: Overall ChaRM Team: Children and Recovering Mothers Monthly multidisciplinary meetings with multiple agencies: impaneled High risk factors:  Increased distance to treatment center  Discontinuation of methadone / buprenorphine  Actively using partner  Abusive relationship with partner  High risk period: 6-9 months post partum Women respond well to positive interactions with health care providers Chittenden Center Mobile Methadone Newport and St. Johnsbury Habit Management

MOTHER Study Maternal Opioid Treatment: Human Experimental Research Funding: NIDA (National Institute for Drug Abuse) Multicenter double-blind randomized controlled study Evaluating methadone vs buprenorphine in pregnant opioid-dependent women Outcome: incidence / severity of NAS

Challenges for the Health Care Provider Recognition of one’s own reactions and feelings Feeling anger towards a substance abusing mother is not uncommon Forming relationships may be difficult due to manipulative behavior (a normal symptom of addiction) Addiction needs to be viewed as a disease, not a chosen way of life

Questions?