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Take home messages on management of
Wilson Disease in the Indian scenario
Chairpersons: Aabha Nagral, Prashanth LK,SK Yachha
Wilson disease and pregnancy
Chairpersons: Aabha Nagral, Prashanth LK,SK Yachha
Talk: RK Dhiman
Wilson’s Disease and Pregnancy
Radha K Dhiman,
MD, DM, FAMS, FACG, FRCP Edin, FRCP London, FAASLD
Department of Hepatology
PGIMER, Chandigarh
Email: [email protected]
Concerns in WD’s Female Patients
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Menstruation,
Marriage, conception, pregnancies,
Recurrent abortions,
Teratogenicity secondary to drugs,
Breast-feeding,
Genetic counseling
Pregnancies in Symptomatic and
Asymptomatic Wilson’s Disease
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N=341, Retrospective
M:F = 239:102 (74 in reproductive age group (15–45
years)
16 women conceived at least once on 59 occasions
7 (31.8%) failed to conceive
Spontaneous abortions - 24 occasions (40.7%)
3 (5.1%) stillbirths
30 (50.8%) successful pregnancies and deliveries in 12
mothers
Sinha S, Neurological Sciences 2004
Pregnancies in Symptomatic and
Asymptomatic Wilson’s Disease
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None of the neurological signs or symptoms
worsened during pregnancy
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6 patients on treatment for several years
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Penicillamine (250 mg/day) and zinc sulphate (1320
mg/day) during pregnancy
No teratogenicity
Sinha S, Neurological Sciences 2004
Fertility
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Amenorrhea, oligomenorrhea, irregular menses,
and multiple miscarriages
Nonspecific consequences of hepatic
dysfunction
Diffusion of non–ceruloplasmin-bound copper
from plasma into tissues, a process that may
affect the ovarian follicular aromatase activity
Kaushanksy A, et al, Fertil Steril 1987
Spontaneous Abortions
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Recurrent spontaneous abortions
Chronic liver disease, endocrinal disorders and
anemia
 Increased copper deposition in uterus prevents
implantation of fetus
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Rate of spontaneous abortion in India is 5%
versus WD - 40.7%
More in untreated group
Scheinberg IH, NEJM 1975; Sinha S, Neurological Sciences 2004
Teratogenicity - Penicillamine
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Documented in laboratory animals and patients
treated for other conditions like RA and cystinuria
Cutis laxa like syndrome, micrognathia, low-set
ears, hyperflexibility of joints, fragile veins,
varicosity and impaired wound healing
Major factor – copper deficiency in the fetus
High proportion of unbound copper, which is
chelated by penicillamine and excreted, thus
effectively reducing the penicillamine levels.
Rosa et al, Teratology 1986; Cohen et al, Drug-Nutr Interact 1983; Keen et al,
Teratology 1983; Mjolnerod et al, Lancet 1971; Solomon et al, MEJM 1977
Breast Feeding
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Women taking D-penicillamine should not
breast-feed
Drug is excreted into breast milk and might
harm the infant.
Little is known about the safety of trientine and
zinc in breast milk.
Pregnancies in Women Taking
Penicillamine
Women Pregnancies Normal Defects
(n)
(n)
Neonates
Wilson’s Disease
Center
43
71
69
2 therapeutic abortions
Case Reports
32
41
38
1 mannosidosis, 1 cleft
lip and palate, 2 transient
Cutis laxa
Walshe
35
40
36
1 premature, 2
Therapeutic abortions, 1
miscarriage
Westermark
1
1
1
111
153
144
Total
Sternlieb, Hepatology 2000
Pregnancies in Women Taking Trientine
Women
(n)
Pregnancies Normal Defects
(n)
Neonates
Wilson’s Disease
Center
4
6
6
Case Reports
2
2
2
Walshe
2
14
11
Total
11
22
19
1 miscarriage, 1
therapeutic abortion, 1
isochromosome x
Sternlieb, Hepatology 2000
Drugs Used in WD
Drug
Advantage Disadvantage
In pregnancy
Penicillamine
[Reductive
Fast acting
20-50% risk of neurologic
worsening
High incidence of toxicity
100% efficacy,
Teratogenic in
animals
Trientine
[Reductive
chelation and
cupruria]
Rapid
action
High incidence of adverse
100% efficacy,
toxicity
Teratogenic in
Moderate incidence of toxicity animals
Zinc
[Induction of
Low
toxicity
Slow acting
Disease progression
chelation and
cupruria]
intestinal cell
metallothionein]
No teratogenicity
EASL/AASLD Recommendation
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Treatment for Wilson’s disease should be
continued during pregnancy, but dosage
reduction is advisable for D-penicillamine and
trientine
EASL - GRADE II-3, B, 1
AASLD - Class I, Level C
Therapy
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Mothers and infants tolerate pregnancy safely,
providing that compliance with the prescribed regimen
is maintained.
Dose
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First 2 trimesters - 0.75 to 1 g of either penicillamine or
trientine
Last trimester - 0.5 g/d
Interruption of therapy carries a high risk of hemolytic
episodes with hepatic insufficiency and fatality for the
mother
Teratogenic effects of either penicillamine or trientine
are not supported by data
Shimono N, et al. Gastroenterol Jpn 1991
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Students/Trainees (MD, DM, DNB and PhDs)
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You
Therapy
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Interruption of therapy carries a high risk of
hemolytic episodes with hepatic insufficiency
and fatality for the mother.
Five successful pregnancies in same women with
WD