ontwenningssyndromen bij de pasgeborene
neonatal withdrawal syndrome
neonatal abstinence syndrome
karel allegaert
UZ Leuven
illicit drug use during pregnancy
6.4 % overall
2.8 % during pregnancy
opioids
90 % 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)
alcohol
effecten op hersenontwikkeling
effecten extra-CNS
gedragsproblematiek
opioids
neonatale abstinentie problematiek
SSRI’s
peripartale effecten van SSRI’s
pathogenese
direct toxische effecten van alcohol
toxische effecten of acetaldehyde
placentaire dysfunctie
? IUGR
prostaglandin synthesis
apotosis (‘geprogrammeerde celdood)
Prenatal Alcohol Exposure
No Effect
Fetal Alcohol
Effects
Alcohol Related
Birth Defects
(ARBD)
Fetal Alcohol
Syndrome
Alcohol Related
Neurodevelopmental
Disorders
(ARND)
Death
Klinische tekens van FAS
Groei
prenatale groeirestrictie
postnatale groeirestrictie
94
96
CZS
microcefalie
ontwikkelingsvertraging
94
89
Faciaal
epicanthus plooi
midfaciale hypoplasie
kort, naar boven gekanteld neusje
hypoplasie philtrum
smalle bovenlip
52
65
75
91
90
Cardiaal
cardiopathie
48
Varia
gehoorsproblematiek (cond + neuro)
oorschelp/gehoorgang afwijkingen
n opticus hypoplasie
75 + 6
23
76
Naar Volpe, Neurology of the Newborn
Zilverkleuring weergave apoptose activiteit CZS
controle vs 24 h na ethanol
Majeure neuropathologische presentaties van FAS
Microcefalie
Migratiestoornissen (neuronaal > gliale)
Midline prosencephalie afwijkingen,
agenesis corpus callosum
septo-optische dysplasie
holoprosencephaly
Neurale buis defecten
zuigeling
verstoorde slaap-waak ritmes
‘excessive arousal’
voedingsproblemen
failure to thrive (groeipotentieel)
schoolgaand kind
hyperactiviteit
aandachtsstoornisen
mentale retardatie
volwassenen
mentale problemen
gedragsproblematiek
geheugenproblematiek
alcohol
effecten op hersenontwikkeling
effecten extra-CNS
gedragsproblematiek
opioids
neonatale 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 aan
uitgebreidheid
karakteristieken
coccaine (XTC)
methadone (opioid)
heroine (opioid)
heroine
vs
methadone
Accurate Observation + Assessment
Supportive Care
a.
Environment of Care
b.
Therapeutic Handling
c.
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 :
step 2 :
stabilisation
reduction
Scores > 12 then Score 2 hourly
Scores remain > 12 for next 2 consecutive scores
Scores < 12
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
Continue Observation
Scoring until discharge
Oral Morphine Regime
Level 6:
Level 5:
Level 4:
Level 3:
Level 2:
Level 1:
60mcg / kg / dose
5omcg / kg / dose
40mcg / kg / dose
30mcg / kg / dose
20mcg / kg / dose
10mcg / kg / dose
Starting Level = level 4
4 hourly
4 hourly
4 hourly
4 hourly
4 hourly
4 hourly
Stabilisation has been achieved when the
infant is consolable, has rhythmic sleep
and feed cycles, a steady weight gain and
is clinically stable
NAS Infant on Morphine Replacement
Calculate Daily the Average Score
DAS < 9
DAS > 9
Reduce to next level of Morphine
Stop Medication after 24 h at level 1
Morphine if DAS < 9
Remain on same
level of Morphine
Observe for further 24 Hours
Scores Remain < 9
Duration of Morphine Therapy in days
Year
Maximum
Minimum
Average
95-96
43
12.6
24.9
96-97
44.4
21.2
32.8
97-98
20.8
3.4
13.7
98-99
18
4.3
7.8
99-00
17.8
3.3
6.8
00-01
18
4.2
8.3*
opioide middelen
‘cold turkey’
timing ifv PK
pathogenese = opioid receptor
onbesproken
maternele verslavingsproblematiek
beschermende maatregelen
andere peripartale medische problemen
wiegendood risico
screeningsmogelijkheden
alcohol
effecten op hersenontwikkeling
effecten extra-CNS
gedragsproblematiek
opioids
neonatale abstinentie problematiek
SSRI’s
(anti-epileptica)
peripartale effecten van SSRI’s
alcohol
effecten op hersenontwikkeling
effecten extra-CNS
gedragsproblematiek
opioids
neonatale 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 ratio
2.Half-life of drug in mother
3.Relative infant dose
4.Half-life of drug in child
Drugs in lactation
Dose
(Dm)
Mothers’ plasma
M/P
Concentration
Infants’plasma
Milk
Dose
(Di)
Time
• 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%
Venlafaxine
Drug info
Maternal dose 75-225 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
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 ratio
2.Half-life of drug in mother
3.Relative infant dose
4.Half-life of drug in child