Consistent with Fetal Warfarin SyndromeTheera Tongsong MD Chanane Wa - PDF document

Consistent with Fetal Warfarin SyndromeTheera Tongsong, MD, Chanane Wanapirak, MD, Wirawit Piyamongkol, MDWarfarin sodium is a low molecular weight anti-coagulant that readily crosses the placenta and mayas warfarin embryopathy or warfarin syndrome.The teratogenic effects may occur from exposuresperiod secondary to destruction of structures thatwere formed normally during embryogenesis. Theirgenesis is probably from hemorrhage into any of sev-eral organs secondary to vitamin K deficiencyThe syndrome is identified intrimester.Although this syndrome is well recog-nized in postnatal series, we report the prenatalsonographic diagnosis of fetal warfarin syndrome.CASE REPORTA20 year old woman, gravida 0, had been diagnosed at 25years. She underwent open commissurotomy 2 years ago.Her cardiac status was currently functional class I accord-ing to the American Heart Association. She had taken war-farin sodium as an anticoagulation prophylaxis, with anaverage daily dosage of 10 mg. In the present pregnancy,she attended an antenatal clinic at a rural hospital.Anticoagulation with warfarin was given throughoutpregnancy. During the antenatal period, anticoagulationwas not switched from warfarin to heparin. At her firstvisit, 25 weeks of gestation, she was healthy, with a func-tional class I cardiac status. The uterine size was appropri-performed on the day of the first visit to rule out fetalabnormalities due to warfarin exposure. Sonographic find-ings revealed a live male fetus, with a gestational age of 25weeks by biparietal diameter (6.3 cm.) and head circum-ference (23.1 cm.). The placenta had a normal appearanceotic fluid was normal. Thorough examination of the fetusfor structural abnormalities was performed. The fetalbiometry revealed FGR, an abdominal circumference of Received January 25, 1999, from the Department of Obstetrics andGynecology, Faculty of Medicine, Chiang Mai University, ChiangMai, Thailand. Revised manuscript accepted for publication April 4,Address correspondence and reprint requests to Theera Tongsong,MD, Department of Obstetrics and Gynecology, Faculty of Medicine,Chiang Mai University, Chiang M

ai 50200, Thailand.ABBREVIATIONSFGR, Fetal growth restriction; SD, Standard deviation; CDPX, X-linked chondrodysplasia punctata 1999 by the American Institute of Ultrasound in Medicine ¥ J Ultrasound Med 18:577Ð580, 1999 ¥ 0278-4297/99/$3.50 brae (Fig. 1) and femoral epiphyses (Fig. 2), with a rela-tively short femur (4.2 cm; centile for 25 weeksÕgestation), nasal hypoplasia with a depressed nasal bridgeon the facial profile view (Fig. 3), and bilateral ventricu-lomegaly with a width of 2 cm (Fig. 4). Aweek later, at 26ic with a complaint of no fetal movement for 1 day.Physical examination found no fetal heartbeat, and repeat-ed ultrasonograms confirmed fetal death. After propervaginal misoprostol. The male baby, weighing 420 g, wasvaginally delivered. The stillborn neonate had a slightlyenlarged head and flattened face, with a depressed nasalfemoral epiphyses. The autopsy revealed no other abnor-malities other than mild hydrocephalus, nasal hypoplasiaWarfarin sodium, a coumarin anticoagulant,depresses synthesis of vitamin KÐdependent clottingfactors (II, VII, IX, X) and is used in the treatment ofa variety of thromboembolic disorders and in thoseat significant risk of thrombus development. Becauseof its low molecular weight, warfarin easily crossesthe placenta, resulting in significant levels in thefetus. Therefore, both mother and fetus are anticoag-ulated. Apattern of congenital anomalies was wellrecognized in several children born to motherstreated with warfarin during pregnancy.most consistent fetal anomalies are nasal hypoplasiaAdditional adverse effects that may develop aftersecond or third trimester exposure include opticatrophy, cataracts, microcephaly, blindness, andgrowth and mental retardation. The risks of neonataldeath, stillbirth, and spontaneous abortion are alsoincreased. The period of greatest susceptibility to theninth postmenstrual weeks of gestation. No epi-demiologic study has been reported that adequatelydefines the risk for this syndrome, but publisheddata regarding warfarin use in pregnancy suggestthat approximately 10% of infants born alive tomothers who take warfarin during pregna

ncy havewarfarin embryopathy.fetal effects, neonatal deaths, stillbirths, spontaneousabortions, and premature delivery occurred inapproximately 31% of treated pregnancies.Timing of exposure appears to be a critical factor.Fetal effects of warfarin therapy during the secondand third trimesters, such as those to the central ner-vous system (including microcephaly, hydro-cephalus, Dandy-Walker malformation) and eyeanomalies, are frequent findings and occur in 578FETALWARFARIN SYNDROME Coronal scan of fetal spines shows stippling of lower Figure 2Scan shows stippling of head of femur and epiphysis. approximately 3% of children born to mothers whoreceived warfarin during pregnancy.Furthermore,the effects of warfarin, which are difficult to reverse,are seen for a considerable period of time afteradministration during pregnancy can cause obviousproblems at the time of labor and delivery. Its uselate in pregnancy causes fetal, placental, or neonatalhemorrhage, especially intraventricular hemor-rhage.sure in utero and sonographic findings, includingintrauterine growth restriction, ventriculomegaly,nasal hypoplasia with depressed nasal bridge, andthe prenatal diagnosis of fetal warfarin syndrome inthe case presented here. Besides the possibility ofprenatal diagnosis of fetal warfarin syndrome, thisreport supports that the drug could not only causeutero.This case report suggests that ultrasonographicgrowth and in possible detection of specific struc-tural anomalies of major organs in cases of warfarinexposure in utero, especially in the first trimester.warfarin syndrome are nasal hypoplasia and stip-syndrome is likely to be visualized by targeted ultra-sonography, with special attention on a facial profileand a thorough bone survey. However, patientsshould be advised of the limitations of prenatal 579 J Ultrasound Med 18:577Ð580, 1999 TONGSONG ET AL Scan of facial profile shows small nose. Transaxial view of skull shows bilateral ventriculo-megaly. Figure 5Postnatal radiograph shows stippling of lower ver-tebrae and femur epiphyses. be detected (e.g., gross structural abnormalities) butalso in its reliability in detect

ing defects prenatally. Anormal ultrasonographic examination cannot ensurepregnancy. Even high detail ultrasonography duringthe second or third trimester may not always identifythe fetal impact of warfarin syndrome. However, ourprenatally and lead to the diagnosis as in chon-drodysplasia punctata.known; however, it probably results from hemor-rhage secondary to vitamin K deficiency induced byThe clinical features like fetal warfarinsyndrome were found in other causes of vitamin KAdditionally, thesimilarity between this syndrome and recessivethese two disorders. Recent evidence that warfarinmined deficiency that is responsible for CDPX,pro-1.Hall JG, Pauli RM, Wilson K: Maternal and fetal sequelaeof anticoagulation during pregnancy. Am J Med 68:122,2.Stevenson RE, Burton M, Ferlauto GJ, et al: Hazards oforal anticoagulants during pregnancy. JAMA243:1549,3.Francho B, Meroni G, Parenti G, et al: Acluster of sulfa-tase genes on Xp22.3: Mutations in chondrodysplasiaopathy. Cell 81:15, 19954.Kaplan LC: Congenital Dandy-Walker malformationassociated with first trimester warfarin: Acase report andliterature review. Teratology 32:333, 19855.Zakzouk MS: The congenital warfarin syndrome. J6.Sareli P, England JM, Berk MR, et al: Maternal and fetalsequelae of anticoagulation during pregnancy in patientswith mechanical heart valve prostesis. Am J Cardiol7.Vitali E, Donatelli F, Quaini E, et al: Pregnancy in patientswith mechanical prosthetic heart valves. J CardiovascSurg 27:221, 19868.Ville Y, Jenkins E, Shearer MJ, et al: Fetal intraventricularhaemorrhage and maternal warfarin. Lancet 341:1211,9.Sherer DM, Glanz, JC, Allen TA, et al: Prenatal sono-graphic diagnosis of chondrodysplasia punctata. Obstet10.Pryde PG, Bawle E, Brandt F, et al: Prenatal diagnosis ofnon-rhizomelic chondrodysplasia punctata (Conradi-HŸnermann syndrome). Am J Med Genet 47:426, 199311.Menger H, Lin AE, Toriello HV, et al: Vitamin K defi-ciency embryopathy: Aphenocopy of the warfarinembryopathy due to a disorder of embryonic vitamin Kmetabolism. Am J Med Genet 72:129, 1997 580FETALWARFARIN SYNDROME Figure 6Postnatal appearance of nasal hypoplasia.