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