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Ontwenningssyndromen bij de pasgeborene neonatal withdrawal syndrome neonatal abstinence syndrome karel allegaert UZ Leuven.

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Presentatie over: "Ontwenningssyndromen bij de pasgeborene neonatal withdrawal syndrome neonatal abstinence syndrome karel allegaert UZ Leuven."— Transcript van de presentatie:

1 ontwenningssyndromen bij de pasgeborene neonatal withdrawal syndrome neonatal abstinence syndrome karel allegaert UZ 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

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

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12 Groeiprenatale groeirestrictie94 postnatale groeirestrictie96 CZSmicrocefalie94 ontwikkelingsvertraging89 Faciaalepicanthus plooi52 midfaciale hypoplasie65 kort, naar boven gekanteld neusje75 hypoplasie philtrum91 smalle bovenlip90 Cardiaalcardiopathie48 Variagehoorsproblematiek (cond + neuro) oorschelp/gehoorgang afwijkingen23 n opticus hypoplasie76 Naar Volpe, Neurology of the Newborn Klinische tekens van FAS

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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)

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22 heroinevsmethadone

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

26 Finnegan score

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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 Observation Scoring until discharge

30 Oral Morphine Regime Level 6:60mcg / kg / dose4 hourly Level 5:5omcg / kg / dose 4 hourly Level 4:40mcg / kg / dose4 hourly Level 3:30mcg / kg / dose4 hourly Level 2:20mcg / kg / dose4 hourly Level 1:10mcg / kg / dose4 hourly Starting Level = level 4

31 Stabilisation has been achieved when the consolablerhythmic sleep infant is consolable, has rhythmic sleep and feed cyclesweight gain and feed cycles, a steady weight gain and clinically stable is clinically stable

32 DAS > 9 Remain on same level of Morphine NAS Infant on Morphine Replacement Calculate Daily the Average Score 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 YearMaximumMinimumAverage *

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

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

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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 callers daily, open to public Each week 10 to 20 women seen in clinic

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 Drugs in lactation Dose (D m ) Milk Infants’plasma Dose (D i ) Time M/P Concentration Mothers’ plasma M/P = milk/plasma ratio Di = Estimated infant dose Concentration m x M/P x Volume milk RID= relative infant dose = Dm (mg/kg/day ) / Di (mg/kg/day) *100%

51 Venlafaxine Drug info Maternal dose mg/day Venlafaxine metabolized to (also active) O-desmethyl-venlafaxine RID (relative infant dose) = 5-7.5% Effect in neonate (n=21) : Serum levels (including metabolite): 1-15% of maternal levels Effect on weight gain n=2 No effects on sleep, behavior or neurodevelopment

52 are all books equal? Farmacotherapeutisch kompas: –Venlafaxine gaat over in de moedermelk. –Tijdens gebruik geen borstvoeding geven. AAP (American Academy of Pediatrics: –the effect on nursing infants is unknown but may be of concern

53 More sources: Briggs: –Refers to AAP guidelines –Monitor for adverse events Lactmed (toxnet.nlm.nih.gov ) –Drug found in plasma of infant –No proven drug-related effect –Monitor for excessive sedation and adequate weight gain –Possibly serum levels to rule out toxicity

54 Drugs and breastfeeding

55 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


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