INTRODUCTION

1. NEONATAL ABSTINENCE SYNDROME DUE TO DEPENDENCY-INDUCING DRUGS. OUR EXPERIENCE WITH METHADONE TREATMENT. V.Sideri, C.Vliora, A.Daskalaki, P.Mexi-Bourna, K.Kleanthous, M.Soulioti, G. Kyrkou, N.Bournas, V.Papaevangelou 3rd Pediatric Clinic of the University of Athens, "Attikon" Hospital, Athens Greece

2. INTRODUCTION Neonates born to mothers taking • OPIOIDS • OTHER DEPENDENCY-INDUCING DRUGS are at an increased risk of developing Neonatal Abstinence Syndrome (NAS) • PHARMACOTHERAPY: 42%-94% of infants exposed in-utero to the substances.

3. NAS: is characterized by a set of symptoms involving • HYPERIRRITABILITY of the CNS (tremors, increase in muscle tone, convulsions, high-pitched crying). • RESPIRATORY SYMPTOMS (tachypnea, retractions, sneezing, nasal congestions) • GASTROINTESTINAL SYMPTOMS ( excessive sucking-poor feeding, vomiting, loosing stools) • AUTONOMIC SYMPTOMS ( mottling, sweating, high temperature, frequent yawing)

4. The most frequent substance • OPIOIDS • SEDATIVES/SOMNIFEROUS • BARBITURATES • ALCOHOL

5. AIM Our aim was to study methadone substitution-treatment of NAS caused by dependency-inducing substances.

6. METHOD • We retrospectively studied NICU hospitalization charts of infants with NAS, during 2008-2013 • We used Finnegan scoring system for scoring NAS symptoms • We repeated the score every 4 hours to monitor signs of withdrawal • We started therapy with methadone if the score was over 8

7. In addition, we used supportive nopharmacologic therapy (dark and quiet environment, slow and gentle handling of these infants, sometimes tight swaddling, small- frequent feedings, holding and rocking) • We encouraged their mothers breastfeeding them (if it was possible and not contraindicated), and also the Kangaroo care and the skin-to-skin position.

8. RESULTS • 7 neonates born to mothers using dependency-inducing medications, during pregnancy ,we admitted, over a five year period. • 5 were girls • 2 were boys • 3 of the mothers had been accepted in a rehab methadone program, • the rest were active drug-users, most of them abusing more than one substance

9. Hepatitis C was present in 71.5% of mothers. • Delivery was through natural labor in 57% • Median pregnancy length was 39.2±1.7weeks • Median birth weight 2765.7±516.12gr • Median head circumference 33.5±1.7cm • 2 neonates were IUGR.

10. All of the aforementioned infants presented with NAS and were treated with oral methadone (except one, who was treated with phenobarbital). • The majority (5/7) began substitution therapy on the 2nd day of life (Finnegan Score ranging from 9-15). • The median length of methadone administration was 37.5±8.9days (29-56 days) • The median hospitalization length was 49.6±7.2days (42-156 days). • Maximum methadone dose was given between the 10th- 15th day of life • Once the treatment was over no relapse occurred

11. There were no complications neither from NAS nor from the methadone administration (excepting the case in which phenobarbital was administered and who subsequently developed seizures on the 13th day of life) • Brain ultrasound was normal • Auditory brainstem responses and otoacoustic emissions were normal, too

12. One infant was initially given TPN • The rest received enteral feeding exhibiting adequate weight gain. • Upon discharge all of the infants had normal growth and development.

13. DISCUSSION • The incidence of in utero exposures to licid opioids and buprenorphine is increasing During 2000-2009 • Maternal opiate use ↑ 1,19→5,63/ 1000 hospital births • NAS ↑ 1,20→3,39/1000 hospital births • Genetic variations of OPRM1 and COMPT genes appear to affect the need for pharmacotherapy and length of stay in neonates with prenatal opioid exposure. (UpTodate 2014)

14. DISCUSSION • A multidisciplinary team of providers care for mothers with substance abuse and their infants (obstretricians, mental health therapists, psychiatrists, pediatricians, nurses, social workers) • Pharmacologic therapy is initiated for infants who, despite adequate supportive care, display significant signs of NAS syndrome • The initial preferred pharmacologic therapy is the use of an oral solution of morphine sulfate or of methadone • Second medications may be required if infants signs are not adequately controlled by single medication therapy ( phenobarbital, clonidine) (UpTodate 2014)

15. CONCLUSIONS • Methadone administration for treating NAS seems to be effective and safe. • Of course a larger cohort needs to be studied.