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: firstname.lastname@example.org
Concerns in WD’s Female Patients Menstruation, Marriage, conception, pregnancies, Recurrent abortions, Teratogenicity secondary to drugs, Breast-feeding, Genetic counseling
Pregnancies in Symptomatic and Asymptomatic Wilson’s Disease Sinha S, Neurological Sciences 2004 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
Pregnancies in Symptomatic and Asymptomatic Wilson’s Disease Pregnancy does not seem to have adverse effect on the clinical course of WD’s Sinha S, Neurological Sciences 2004 • None of the neurological signs or symptoms worsened during pregnancy • 6 patients on treatment for several years • Penicillamine (250 mg/day) and zinc sulphate (1320 mg/day) during pregnancy • No teratogenicity
Fertility Kaushanksy A, et al, Fertil Steril 1987 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
Spontaneous Abortions Scheinberg IH, NEJM 1975; Sinha S, Neurological Sciences 2004 • Recurrent spontaneous abortions • Chronic liver disease, endocrinal disorders and anemia • Increased copper deposition in uterus prevents implantation of fetus • Rate of spontaneous abortion in India is 5% versus WD - 40.7% • More in untreated group
Teratogenicity - Penicillamine 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 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.
Breast Feeding 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 Sternlieb, Hepatology 2000
Pregnancies in Women Taking Trientine Sternlieb, Hepatology 2000
EASL/AASLD Recommendation 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 Outcome of pregnancy in women with Wilson’s disease is determined by compliance with the prescribed regimen or deviation from it, rather than the choice of medication. Shimono N, et al. Gastroenterol Jpn 1991 • Mothers and infants tolerate pregnancy safely, providing that compliance with the prescribed regimen is maintained. • Dose • 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
AASLD Save Dates Many sessions for Pediatric Gastroenterology and Hepatology Complementary “Registration, Accommodation and Travel” for Students/Trainees (MD, DM, DNB and PhDs)
Therapy 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