illicit drug use during pregnancy 6.4 % overall 2.8 % during pregnancy opioids

1. ontwenningssyndromen bij de pasgeboreneneonatal withdrawal syndromeneonatal abstinence syndromekarel allegaertUZ Leuven

2. illicit drug use during pregnancy 6.4 % overall 2.8 % during pregnancy opioids 90 % symptoms medical treatment SSRI’s

3. Definitie ? A generalized disorder characterized by central nervous system hyper-irritability, gastro-intestinal dysfunction, respiratory distress and vague autonomic symptoms Finnegan & Weiner (1993)

4. alcohol effecten op hersenontwikkeling effecten extra-CNS gedragsproblematiek opioids neonatale abstinentie problematiek SSRI’s peripartale effecten van SSRI’s

10. pathogenese direct toxische effecten van alcohol toxische effecten of acetaldehyde placentaire dysfunctie ? IUGR prostaglandin synthesis apotosis (‘geprogrammeerde celdood)

12. Klinische tekens van FAS Groei prenatale groeirestrictie 94 postnatale groeirestrictie 96 CZS microcefalie 94 ontwikkelingsvertraging 89 Faciaal epicanthus plooi 52 midfaciale hypoplasie 65 kort, naar boven gekanteld neusje 75 hypoplasie philtrum 91 smalle bovenlip 90 Cardiaal cardiopathie 48 Varia gehoorsproblematiek (cond + neuro) 75 + 6 oorschelp/gehoorgang afwijkingen 23 n opticus hypoplasie 76 Naar Volpe, Neurology of the Newborn

15. Zilverkleuring weergave apoptose activiteit CZS controle vs 24 h na ethanol

16. Majeure neuropathologische presentaties van FAS Microcefalie Migratiestoornissen (neuronaal > gliale) Midline prosencephalie afwijkingen, agenesis corpus callosum septo-optische dysplasie holoprosencephaly Neurale buis defecten

17. zuigeling verstoorde slaap-waak ritmes ‘excessive arousal’ voedingsproblemen failure to thrive (groeipotentieel) schoolgaand kind hyperactiviteit aandachtsstoornisen mentale retardatie volwassenen mentale problemen gedragsproblematiek geheugenproblematiek

18. alcohol effecten op hersenontwikkeling effecten extra-CNS gedragsproblematiek opioids neonatale abstinentie problematiek SSRI’s (anti-epileptica) peripartale effecten van SSRI’s

19. A generalized disorder characterized by central nervous system hyper-irritability, gastro-intestinal dysfunction, respiratory distress and vague autonomic symptoms symptomen gerelateerd aan uitgebreidheid karakteristieken coccaine (XTC) methadone (opioid) heroine (opioid)

22. heroine vs methadone

25. Accurate Observation + Assessment Supportive Care a. Environment of Care b. Therapeutic Handling c. Symptomatic Care Pharmacological Intervention

26. Finnegan score

28. Detoxification Detoxification should be undertaken with the maximum speed that can be tolerated by the infant, causing minimal distress to avoid prolonged hospitalisation and prolonged separation from family step 1 : stabilisation step 2 : reduction

29. Scores > 12 then Score 2 hourly Scores remain > 12 for next 2 consecutive scores Start Oral Morphine 4 hourly Starting Level : Level 4 Scores Remain > 12 for next 2 consecutive scores Increase Morphine to next level ( i.e. Level 5 ) Scores Stabilise < 12 = REDUCTION Scores < 12 Continue ObservationScoring until discharge

30. Oral Morphine Regime Level 6: 60mcg / kg / dose 4 hourly Level 5: 5omcg / kg / dose 4 hourly Level 4: 40mcg / kg / dose 4 hourly Level 3: 30mcg / kg / dose 4 hourly Level 2: 20mcg / kg / dose 4 hourly Level 1: 10mcg / kg / dose 4 hourly Starting Level = level 4

31. Stabilisation has been achieved when the infant isconsolable, hasrhythmic sleep and feed cycles, a steadyweight gainand isclinically stable

32. NAS Infant on Morphine Replacement Calculate Dailythe Average Score DAS > 9 Remain on samelevel of Morphine DAS < 9 Reduce to next level of Morphine Stop Medication after 24 h at level 1 Morphine if DAS < 9 Observe for further 24 Hours Scores Remain < 9

33. Duration of Morphine Therapy in days

34. opioide middelen ‘cold turkey’ timing ifv PK pathogenese = opioid receptor onbesproken maternele verslavingsproblematiek beschermende maatregelen andere peripartale medische problemen wiegendood risico screeningsmogelijkheden

37. alcohol effecten op hersenontwikkeling effecten extra-CNS gedragsproblematiek opioids neonatale abstinentie problematiek SSRI’s (anti-epileptica) peripartale effecten van SSRI’s

43. alcohol effecten op hersenontwikkeling effecten extra-CNS gedragsproblematiek opioids neonatale abstinentie problematiek SSRI’s (anti-epileptica) peripartale effecten van SSRI’s

44. Teratology • Around 50% of all pregnancies in Western world are UNPLANNED • ‘Baseline risk’ - in general population for major congenital malformation is 1-3% • A teratogen is an agent that may have harmful effects on the developing fetus

45. Canada's leading teratology research and counseling program • 150-200 callers daily, open to public • Each week 10 to 20 women seen in clinic • www.motherisk.org

46. The developing human

47. Breastfeeding: case 2 • Woman 34 yrs old, G1P1 • History: major depression • No Rx during pregnancy • Couple of weeks after delivery Postnatal depression: Rx venlafaxine (Efexor) • Breastfeeding compatible? te Winkel et al. Farmacotherapie bij kinderen, 2010, 25-27

48. Guideline for drug therapy during lactation • Is drug therapy really necessary? • Choose the safest drug • Risk to infant possible? • Consider blood levels • Consider monitoring child • Minimize exposure by taking drug right after breastfeeding

49. Q2. Which parameter is best indicator for risk to baby? • Milk:plasma ratio • Half-life of drug in mother • Relative infant dose • Half-life of drug in child

50. Dose (Dm) Infants’plasma Milk M/P Dose (Di) Time Drugs in lactation Mothers’ plasma Concentration • M/P = milk/plasma ratio • Di = Estimated infant dose • Concentrationm x M/P x Volumemilk • RID= relative infant dose = Dm (mg/kg/day ) / Di (mg/kg/day) *100%