April 2000, Vol107, pp. 519-523Epid

April 2000, Vol107, pp. 519-523
Epidemiological assessment of misoprostol teratogenicity
*ICda M. Orioli Professor, t SEduardo E. Castilla Professor
*Department of Genetics, Federal University of Rio de Janeiro; TDeparment of Genetics, Oswaldo Cruz Institute, Ria de Janeiro,
Brazil; $Centre of Medical Education and Clinical Investigations, Buenos Aires, Argentina
Objective To verify if any of the 15 congenital defects already reported in association with misoprostol can be
Design
Methods Comparison of misoprostol exposure for each specific defect, using the exposure for the rest of defects as
a reference group.
Population Four thousand six hundred seventy-three consecutive newborn infants with malformations of unknown
aetiology, in the Latin American Collaborative Study of Congenital Malformation.
Results There was no difference in exposure rate between the malformed (34/4673) and nonmalformed (23/4980)
newborns. Four of the five more frequently cited defects in the literature were found to be in excess: constriction
ring, terminal transverse-limb defects, hydrocephalus, and arthrogryposis. Equinovarus feet had a normal frequency
in our study. Thirteen different defects not described in the literature were seen in our misoprostol
exposed cases, but only holoprosencephaly and bladder exstrophy significantly exceeded the expected number.
Conclusions The confirmation from an epidemiological registry of an association for four of the five more commonly
observed congenital defects among misoprostol exposed children described in the literature seems indicative
of a real teratogenic effect. The defects are of vascular disruption type. However, additional attempts to
achieve abortion could not be excluded as a concurrent contribution.
found within an epidemiological registry of congenital defects.
Case-control study including case-sick and case-health controls.
INTRODUCTION
Misoprostol, a synthetic prostaglandin El analogue, has
been illegally used since, at least, 1988 to interrupt
unwanted pregnancies in Brazil and The
report by Gonzalez et aL3 increased to 53 the number of
malformed children attributable to prenatal misoprostol
use. Considering the previous five case reports in the literature,
there are now 15 specific congenital defects
implicated from misoprostol expo~ure'~~-'.
Collins and Mahoney4 published the first case of congenital
malformations, (hydrocephalus, finger reduction
defect, and equinovarus feet) being attributable to
prostaglandin 15-methyl F,a use at seven weeks after
conception. Another fetus exposed to prostaglandin E,
and oxytocin at 15 weeks also had hydrocephalus and
growth retardation5. A fronto-temporal defect with an
asymmetric, well-circumscribed deficiency of the cranium
and overlapping scalp was associated with prenatal
exposure to misoprostol in a dubious number of cases by
a single group of observer^^.^.^. Gonzalez et al.' presented
seven cases with prenatal exposure to misoprostol, six of
them with limb deficiency with or without Mobius
sequence, and one with only facial nerve palsy, propos-
Correspondence: Professor

Hasil (Bahasa Indonesia) 1:

April 2000, Vol107, ms. 519-523Epidemiologi penilaian misoprostol teratogenicity* Profesor ICda M. Orioli, t SEduardo E. Castilla Profesor* Bagian genetika Federal University of Rio de Janeiro; TDeparment genetika, Oswaldo Cruz Institute, Ria de Janeiro,Brasil; $Centre pendidikan kedokteran dan penyelidikan klinis, Buenos Aires, ArgentinaTujuan untuk memverifikasi jika salah satu cacat bawaan 15 sudah dilaporkan dalam hubungannya dengan misoprostol dapatDesainPerbandingan metode misoprostol eksposur untuk setiap cacat tertentu, menggunakan eksposur untuk sisa cacat sebagaikelompok referensi.Populasi empat ribu enam ratus tujuh puluh tiga berturut-turut bayi dengan kecacatan tidak diketahuipada etiologi, di Amerika Latin kolaboratif studi dari bawaan malformasi.Hasil ada adalah ada perbedaan dalam tingkat eksposur antara kecacatan (34/4673) dan nonmalformed (23/4980)bayi yang baru lahir. Empat dari lima Cacat lebih sering dikutip dalam literatur yang ditemukan untuk menjadi berlebihan: penyempitancincin, terminal melintang-ekstremitas Cacat, hidrosefalus, dan arthrogryposis. Equinovarus kaki memiliki frekuensi yang normaldalam studi kami. Tiga belas cacat yang berbeda yang tidak dijelaskan di dalam literature yang terlihat di misoprostol kamikasus terbuka, tetapi hanya holoprosencephaly dan kandung kemih exstrophy secara signifikan melebihi jumlah yang diharapkan.Kesimpulan konfirmasi dari registry epidemiologi Asosiasi untuk empat dari lima lebih seringobserved congenital defects among misoprostol exposed children described in the literature seems indicativeof a real teratogenic effect. The defects are of vascular disruption type. However, additional attempts toachieve abortion could not be excluded as a concurrent contribution.found within an epidemiological registry of congenital defects.Case-control study including case-sick and case-health controls.INTRODUCTIONMisoprostol, a synthetic prostaglandin El analogue, hasbeen illegally used since, at least, 1988 to interruptunwanted pregnancies in Brazil and Thereport by Gonzalez et aL3 increased to 53 the number ofmalformed children attributable to prenatal misoprostoluse. Considering the previous five case reports in the literature,there are now 15 specific congenital defectsimplicated from misoprostol expo~ure'~~-'.Collins and Mahoney4 published the first case of congenitalmalformations, (hydrocephalus, finger reductiondefect, and equinovarus feet) being attributable toprostaglandin 15-methyl F,a use at seven weeks afterconception. Another fetus exposed to prostaglandin E,and oxytocin at 15 weeks also had hydrocephalus andgrowth retardation5. A fronto-temporal defect with anasymmetric, well-circumscribed deficiency of the craniumand overlapping scalp was associated with prenatalexposure to misoprostol in a dubious number of cases bya single group of observer^^.^.^. Gonzalez et al.' presentedseven cases with prenatal exposure to misoprostol, six ofthem with limb deficiency with or without Mobiussequence, and one with only facial nerve palsy, propos-Correspondence: Professor