ontwenningssyndromen bij de pasgeborene

neonatal withdrawal syndromeneonatal abstinence syndrome

karel allegaertUZ Leuven

illicit drug use during pregnancy

6.4 % overall2.8 % during pregnancy

opioids90 % symptoms

medical treatment

SSRI’s

Definitie ?

A generalized disorder characterized by

central nervous system hyper-irritability, gastro-intestinal dysfunction, respiratory distress and vague autonomic symptoms

Finnegan & Weiner (1993)

alcoholeffecten op hersenontwikkelingeffecten extra-CNSgedragsproblematiek

opioidsneonatale abstinentie problematiek

SSRI’speripartale effecten van SSRI’s

pathogenese

direct toxische effecten van alcohol

toxische effecten of acetaldehyde

placentaire dysfunctie

? IUGR

prostaglandin synthesis

apotosis (‘geprogrammeerde celdood)

N o E ffec t

A lcoh o l R e la tedB irth D e fec ts

(A R B D )

A lcoh o l R e la tedN eu rod eve lop m en ta l

D iso rd ers(A R N D )

F eta l A lcoh o lE ffec ts

Fetal AlcoholSyndrom e

D eath

P ren ata l A lcoh o l E xp osu re

Groei prenatale groeirestrictie 94postnatale groeirestrictie 96

CZS microcefalie 94ontwikkelingsvertraging 89

Faciaal epicanthus plooi 52midfaciale hypoplasie 65kort, naar boven gekanteld neusje 75hypoplasie philtrum 91smalle bovenlip 90

Cardiaal cardiopathie 48

Varia gehoorsproblematiek (cond + neuro) 75 + 6oorschelp/gehoorgang afwijkingen 23n opticus hypoplasie 76

Naar Volpe, Neurology of the Newborn

Klinische tekens van FAS

Zilverkleuring weergave apoptose activiteit CZScontrole vs 24 h na ethanol

Majeure neuropathologische presentaties van FAS

Microcefalie

Migratiestoornissen (neuronaal > gliale)

Midline prosencephalie afwijkingen,agenesis corpus callosumsepto-optische dysplasieholoprosencephaly

Neurale buis defecten

zuigelingverstoorde slaap-waak ritmes‘excessive arousal’voedingsproblemenfailure to thrive (groeipotentieel)

schoolgaand kindhyperactiviteitaandachtsstoornisenmentale retardatie

volwassenenmentale problemen gedragsproblematiekgeheugenproblematiek

alcoholeffecten op hersenontwikkelingeffecten extra-CNSgedragsproblematiek

opioidsneonatale abstinentie problematiek

SSRI’s (anti-epileptica)peripartale effecten van SSRI’s

A generalized disorder characterized by

central nervous system hyper-irritability, gastro-intestinal dysfunction, respiratory distress and vague autonomic symptoms

symptomen gerelateerd aanuitgebreidheid karakteristieken

coccaine (XTC)methadone (opioid)heroine (opioid)

heroine vs methadone

Accurate Observation + Assessment

Supportive Care

a. Environment of Careb. Therapeutic Handlingc. Symptomatic Care

Pharmacological Intervention

Finnegan score

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 : stabilisationstep 2 : reduction

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

Oral Morphine RegimeOral Morphine Regime

Level 6: 60mcg / kg / dose 4 hourlyLevel 5: 5omcg / kg / dose 4 hourlyLevel 4: 40mcg / kg / dose 4 hourlyLevel 3: 30mcg / kg / dose 4 hourlyLevel 2: 20mcg / kg / dose 4 hourlyLevel 1: 10mcg / kg / dose 4 hourly

Starting Level = level 4

Stabilisation has been achieved when theinfant is consolableconsolable, has rhythmic sleeprhythmic sleepand feed cyclesand feed cycles, a steady weight gainweight gain andis clinically stableclinically stable

DAS > 9

Remain on samelevel 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

Duration of Morphine Therapy in days

Year Maximum

Minimum Average

95-96 43 12.6 24.996-97 44.4 21.2 32.897-98 20.8 3.4 13.798-99 18 4.3 7.899-00 17.8 3.3 6.800-01 18 4.2 8.3*

opioide middelen

‘cold turkey’ timing ifv PKpathogenese = opioid receptor

onbesprokenmaternele verslavingsproblematiekbeschermende maatregelenandere peripartale medische problemenwiegendood risicoscreeningsmogelijkheden

alcoholeffecten op hersenontwikkelingeffecten extra-CNSgedragsproblematiek

opioidsneonatale abstinentie problematiek

SSRI’s (anti-epileptica)peripartale effecten van SSRI’s

alcoholeffecten op hersenontwikkelingeffecten extra-CNSgedragsproblematiek

opioidsneonatale abstinentie problematiek

SSRI’s (anti-epileptica)peripartale effecten van SSRI’s

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

• 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

The developing human

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

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

Q2. Which parameter is best indicator for risk to baby?1.Milk:plasma ratio2.Half-life of drug in mother3.Relative infant dose4.Half-life of drug in child

Drugs in lactation

Dose(Dm)

Milk Infants’plasma

Dose

(Di)

Time

M/P

Conc

entr

atio

n

Mothers’ plasma

• 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%

VenlafaxineDrug info

Maternal dose 75-225 mg/dayVenlafaxine metabolized to (also active) O-desmethyl-venlafaxineRID (relative infant dose) = 5-7.5%

Effect in neonate (n=21) :

Serum levels (including metabolite): 1-15% of maternal levelsEffect on weight gain n=2No effects on sleep, behavior or neurodevelopment

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

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

Drugs and breastfeeding

Q2. Which parameter is best indicator for risk to baby?1.Milk:plasma ratio2.Half-life of drug in mother3.Relative infant dose4.Half-life of drug in child