AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY 28:245-246 © 1992 MUNKSGAARD

Colchicine Treatment in Conception and Pregnancy: Two Hundred Thirty-one Pregnancies in Patients With Familial Mediterranean Fever OSVALDORABINOVITCH, DEBORAH ZEMER, EHUD KUKlA, EZRA SOHAR, AND SHLOMO MASHIACH Department of Gynecology and Obstetrics and the Keller Institute of Medical Research, Sheba Medical Center, Tel-Aviv University Medical School, Tel-Aviv, Israel ABSTRACT: The effect of maternal use of colchicine on fetuses is unknown. The children of 116 women with Familial Mediterranean Fever (225 completed pregnancies) were studied. There was no unusual frequency of fetal abnormality among women taking colchicine before or during pregnancy. Colchicine treatment does not apparently harm mother or child. (Am J Reprod Immunol. 1992; 28:245-246.) Key words: Familial Mediterranean Fever, colchicine, amyloidosis, pregnancy INTRODUCTION

Familial Mediterranean Fever (FMF) is an ethnically restricted genetic disease. Manifestations appear early in life, in two-thirds of patients before age two. The disease has two phenotypically independent manifestations: (1) acute, short-lived painful, febrile attacks, accompanied by peritonitis, pleuritis or arthritis, and (2) nephropathic AA-amyloidosis which leads to terminal renal failure early in life.! Chronic colchicine treatment, introduced in 1973, prevents both the attacks and the fetal amyloidosis.v" Arrest of colchicine treatment not only precipitates abrupt exacerbation of the febrile attacks but also enhances development of amyloidosis. Therefore arrest of colchicine treatment for several months or more prior to conception and during pregnancy is not practical. Colchicine-treated patients planning pregnancy were offered care at a special obstetric FMF-clinic established in our hospital. The experience of this clinic with conceptions and pregnancies in colchicine-treated women is reported. MATERIALS AND METHODS

One hundred sixteen female patients registered at the National FMF Center at the Sheba Medical Center were seen at the obstetric clinic during at least one pregnancy. They are the focus of this study. Data concerning previous pregnancies were culled from history and hospital charts and are not always complete. In the first four years (1973-1977) after introduction of colchicine as treatment (1 to 2 mg per day), patients were advised to discontinue the drug when pregnancy was planned. However, most patients did not follow our advice and many women conceived while on colchicine and discontinued the drug after conception, during the first trimester of pregnancy. In 1977 we decided to continue colchicine treatment throughout pregnancy, and to perform amniocentesis to detect possible fetal abnormalities.

Submitted for publication June 26, 1992; accepted June 30, 1992. Address reprint requests to Deborah Zemer, M.D., Keller Institute of Medical Research, Tel-Hashomer 52621, Israel.

Patients are presented in three groups: group A, colchicine treatment throughout pregnancy; group B, colchicine treatment at conception and discontinued in the first trimester; and group C, pregnancies in untreated patients. The clinic's routine included general gynecological and obstetric history; physical and vaginal examination, routine blood chemistry, including kidney function tests every trimester; maternal serum and o-feto-protein around 17th week of gestation; amniocentesis at 17 to 18th week of gestation; ultrasound examination at 19 to 21st week and at 30 to 32ndweek, and monthly visits. The 116 women who participated in this study had 225 pregnancies that resulted in live births and 70 abortions (35 spontaneous and 25 induced). RESULTS

Of the 225 pregnancies ending in live births, colchicine was taken to term in 91 (group A), and in 40 colchicine was taken at the time of conception and discontinued during the first trimester (group A). Ninety-four pregnancies occurred before colchicine treatment was introduced and serve as controls (group B). Mean age of the colchicine treated women at the time of conception was 27.4 ± 4.5 years, that ofthe untreated women was 24.7 ± 3.5 (P < 0.0002). Twenty-seven pregnancies occurred in women who were treated with continuous chronic colchicine treatment for more than 10 years prior to conception, in 47 between six to 10 years and in 47 less than five years. Length of treatment could not be established in ten. Percentage of spontaneous abortion in the treated women was 12.2% (16 abortions) and 20.2% in the untreated (19 abortions). Of the induced abortions, two were performed because of renal failure due to FMF amyloidosis, one because of rubella, and one because of trisomy 21 found in amniocentesis. The other induced abortions were performed for nonmedical reasons. Two cases of toxemia occurred in the treated group. In both cases Cesarean sections were performed. There were no significant differences in length of pregnancy and birth weight between the three groups (Tables I and 11). Thirty-eight Cesarean sections were performed (16.8% of all deliveries): 20 (21.9%) in group A, nine (22.5%) in group B, and nine (9.6%) in group G. Indications for Cesarean section in each group are shown in Table III. In the fully-treated group, (A), 66 amniocenteses were performed (72.5%); trisomy 21 was found in one 25-yearold patient and abortion was performed (see above). Fetal examination confirmed the diagnosis. A baby with Down's syndrome was born to a 27-year-old partiallytreated mother prior to the period when amniocenteses were performed routinely. The 130 offspring of the treated mothers have been followed in our FMF outpatient clinic. Seventeen are now

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TABLE I. Gestational Age at Delivery (% in Each Group at Three Time Periods)" Week Group A GroupB GroupC

Colchicine treatment in conception and pregnancy: two hundred thirty-one pregnancies in patients with familial Mediterranean fever.

The effect of maternal use of colchicine on fetuses is unknown. The children of 116 women with Familial Mediterranean Fever (225 completed pregnancies...
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