The fetal warfarin syndrome, also known as warfarin embryopathy or di Sala syndrome is caused by fetal exposure to warfarin, an anti-vitamin K anticoagulant used for thromboembolic disorders treatment and prophylaxis, leading to a series of complex malformations, as well as neurological and mental impairment. The disease is more severe if exposure occurs during the first trimester of pregnancy.
Presentation
The presentation of the fetal warfarin syndrome depends on the quantity of the drug that the mother has ingested, the teratogenicity being dose dependent [1] and the duration of the fetal exposure to warfarin. The greatest risk is encountered during the sixth and the ninth week of gestation [2] [3]. The drug has a low molecular weight and crosses the placenta, causing vitamin K deficiency in the embryo or fetus. The mother can present for spontaneous abortion or the pregnancy can be carried to term, but the child may be born dead or die during the neonatal period [4]. When the child survives, he or she has a series of congenital abnormalities [5] [6]. The facial traits of a fetal warfarin syndrome-affected child include nasal hypoplasia, nose bridge depression, the presence of a groove between the tip of the nose and the alae nasi. Small nostrils resulting from these abnormalities may impair air flow and cause neonatal respiratory distress, that may be severe enough to require intervention. Osseous stippling occurs in the axial skeleton and femurs [7]. It may be accompanied by scoliosis and hypoplasia of the extremities, ranging from rhizomelia to dystrophic nails. Central nervous system and eye malformations occur more frequently when the fetus has been exposed to warfarin during the second and third trimesters of pregnancy. Abnormalities consist of hydrocephalus, microcephaly, corpus callosum agenesis, microphthalmia and optic atrophy. Blindness, deafness, and seizures, as well as severe bleeding at birth, not predictable from the maternal international normalized ratio, may also be seen [8] [9]. Other teratogenic effects of warfarin include cardiac and laryngeal abnormalities, aortic coarctation, situs inversus totalis, ventral midline dysplasia, bilobed lungs, congenital cataract, short neck, cleft palate and/or lip [10], mental retardation, feeding difficulties, widely spaced nipples and the Dandy-Walker malformation. Hypotonia or muscular spasticity may be encountered. These children usually fail to thrive.
Entire Body System
- Coarctation of the Aorta
[…] of aorta Fetal hydantoin syndrome ventricular septal defect, tetralogy of Fallot, pulmonary stenosis, patent ductus arteriosus, atrial septal defect, coarctation of aorta Fetal rubella syndrome Pulmonary stenosis, peripheral pulmonary stenosis, patent [pedcard.rush.edu]
Congenital heart defects such as a thinned atrial septum, coarctation of the aorta, patent ductus arteriosus; a connection between the pulmonary artery and aorta occur in 8% of fetal warfarin syndrome patients. [en.wikipedia.org]
- Multiple Congenital Anomalies
G. (1977) Multiple congenital anomalies associated with oral anticoagulants. American Journal of Obstetrics and Gynecology, 127: 191–198. Spranger, J. W., Opitz, J. M. and Bidder, U. (1971) Heterogeneity of chondrodysplasia punctata. [cambridge.org]
Respiratoric
- Saddle Nose
FETAL WARFARIN SYNDROME • Saddle nose • Retarded growth • Defects of limbs, eyes and central nervous system 28. Tetracycline- Teeth and bone damage • Yellow staining • Enamel hypoplasia • Caries and pigmentation of permanent teeth 29. [slideshare.net]
Gastrointestinal
- Failure to Thrive
[…] to thrive Numerology Chaldean Numerology The numerical value of fetal warfarin syndrome in Chaldean Numerology is: 6 Pythagorean Numerology The numerical value of fetal warfarin syndrome in Pythagorean Numerology is: 4 Images & Illustrations of fetal [definitions.net]
[…] to thrive Causes - Fetal warfarin syndrome Not supplied. [checkorphan.org]
Symptoms and Signs Symptoms include low birth weight, seizures, reduced muscle tone, deafness, feeding difficulty, shortened fingers, widely spaced nipples, and failure to thrive. Warfarin ingestion may also be chronic or acute. [dianamossop.com]
Symptoms & Signs Symptoms include low birth weight, seizures, reduced muscle tone, deafness, feeding difficulty, shortened fingers, widely spaced nipples & failure to thrive. Warfarin ingestion may also be chronic or acute. [signssymptoms.org]
Additionally, warfarin can cause birth defects such as abnormal development of the spine, changes to bones in the face (especially the nose), intellectual disability, and failure to thrive. [diseaseinfosearch.org]
Cardiovascular
- Acrocyanosis
After admission to NICU, baby had mild respiratory distress with mild acrocyanosis and intercostal recessions HR: 145/min, RR: 70/min, PP: well felt, BP: 66/40 mmHg, SpO2: 90 % at room air. [jemds.com]
- Systolic Murmur
(Fig: 7, 8, 9) In systemic examination, CVS examination showed a systolic murmur of grade 3/6 with all other systems within normal limits. [jemds.com]
Jaw & Teeth
- High Arched Palate
Head to toe examination it was observed that the baby has depressed nasal bridge, a high arched palate, short neck. Detailed laboratory evaluation was done. Ultrasound of brain and abdomen were normal. [jemds.com]
- Mouth Breathing
Speech and language assessment revealed high palate, mouth breathing, little nasal patency, and shortened upper lip. [ncbi.nlm.nih.gov]
Musculoskeletal
- Brachydactyly
He also had short limbs, brachydactyly, nail hypoplasia, and calcifications in the epiphyseal regions of humeri, femora and vertebrae radiographically. The patient eventually died from respiratory failure at 6 months of age. [ncbi.nlm.nih.gov]
Reported clinical features include: facial anomalies nasal bone hypoplasia nasal bridge depression skeletal anomalies stippled non-calcified epiphyses shortened fingers: brachydactyly nail hypoplasia scoliosis central nervous system intellectual disability [radiopaedia.org]
Affected children also have a hypoplastic nose, eye abnormalities, mental retardation, brachydactyly, and scoliosis. [aippg.net]
Embryopathy symptoms include: Chondrodysplasia, brachydactyly, microcephaly and eye damage. Warfarin in the first trimester is absolutely contraindicated. The most critical period is between 6 to 9 weeks of gestation. [thrombophiliac.com]
Ears
- Hearing Impairment
Less often, affected individuals exhibit hearing impairment, incomplete closure of the roof of the mouth (cleft palate), misalignment of the eyes (strabismus), structural malformations of the heart (congenital heart defects), mild intellectual disability [rarediseases.org]
Breast
- Widely Spaced Nipples
spaced nipples, Deafness, Feeding difficulty, Failure to thrive Numerology Chaldean Numerology The numerical value of fetal warfarin syndrome in Chaldean Numerology is: 6 Pythagorean Numerology The numerical value of fetal warfarin syndrome in Pythagorean [definitions.net]
spaced nipples and the Dandy-Walker malformation. [symptoma.com]
spaced nipples * Deafness * Feeding difficulty * Failure to thrive Causes - Fetal warfarin syndrome Not supplied. [checkorphan.org]
Symptoms and Signs Symptoms include low birth weight, seizures, reduced muscle tone, deafness, feeding difficulty, shortened fingers, widely spaced nipples, and failure to thrive. Warfarin ingestion may also be chronic or acute. [dianamossop.com]
Symptoms & Signs Symptoms include low birth weight, seizures, reduced muscle tone, deafness, feeding difficulty, shortened fingers, widely spaced nipples & failure to thrive. Warfarin ingestion may also be chronic or acute. [signssymptoms.org]
Face, Head & Neck
- Depressed Nasal Bridge
The baby was well, except for facial dysmorphism in the form of depressed nasal bridge, narrow nares and suspected left choanal atresia. [ncbi.nlm.nih.gov]
The symptoms are Nasal hypoplasia, Depressed nasal bridge, Deep groove between nostril and nasal tip, Stippling of uncalcified epiphyses during first year, Mild hypoplasia of nails, Shortened fingers, Low birth weight, Significant mental retardation, [definitions.net]
Symptoms - Fetal warfarin syndrome * Nasal hypoplasia * Depressed nasal bridge * Deep groove between nostril and nasal tip * Stippling of uncalcified epiphyses during first year * Mild hypoplasia of nails * Shortened fingers * Low birth weight * Significant [checkorphan.org]
Facial Anomalies: Depressed nasal bridge and nasal hypoplasia. Skeletal Anomalies: Stippling of non calcified epiphyses. Shortened fingers and hypoplasia of the nails. [fetalultrasound.com]
Neurologic
- Grunting
Baby had mild respiratory distress with intercostal recessions and acrocyanosis but no grunting. Thus in view of prematurity, bad obstetric history, mild respiratory distress and being a precious baby, the baby was shifted to NICU. [jemds.com]
Urogenital
- Pelvic Pain
Brand new chapters provide up-to-date, comprehensive coverage of topics relevant to current practice: -First Trimester Fetal Anatomy -Obstetric Ultrasound and the Obese Patient -Evaluation of Pelvic Pain in the Reproductive Age Patient -Gynecologic Ultrasound [books.google.de]
Workup
Fetal warfarin syndrome diagnosis is mostly based on pregnancy history and clinical examination. However, skeleton radiographs can provide additional information, such as the epiphyseal stippling of vertebrae, long bones, and sacrum. These findings are transient and disappear as the child grows older [11]. Scoliosis, as well as short limbs and digits, can also be noticed on radiological films [12]. Epiphyses can be found to be non calcified. These findings are present in 5-12% of infants who were exposed to warfarin between the sixth and the ninth week of gestation.
Ultrasound
- Ovarian Mass
Features new practice guidelines for obstetric evaluation (including first trimester assessment) and gynecologic management (including evaluation of the endometrium and of ovarian masses). [books.google.de]
Treatment
The newborn presented with skeletal abnormalities and a ventricular septal defect that have not required specific treatment during the first year of life. [ncbi.nlm.nih.gov]
Treatment : How to Treat "Fetal warfarin syndrome"? Teartment for fetal warfarin syndrome includes general avoidance to drugs that are known to enhance bleeding as well as increase metabolism of the anticoagulant drug. [signssymptoms.org]
CLOSE Medical Disclaimer The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. [diseaseinfosearch.org]
Prepare for clinical challenges and save time in addressing them thanks to expert advice on treatment options from international contributors. [books.google.com]
If you believe that you are suffering from any of the symptoms of Fetal warfarin syndrome it is important that you obtain an accurate diagnosis from a medical professional to ensure that you obtain the correct medication or treatment for your condition [medigest.uk]
Prognosis
Ovulation Tests o Home Fertility Tests o Home Rhesus/RH Blood Type Tests o Home Fetal Tests * Fertility-related Home Testing: o Home Ovulation Tests o Home Fertility Tests * Male Fertility Tests o Home Sperm Tests o Sperm Count Tests o Sperm Motility Tests Prognosis [checkorphan.org]
Mild forms of the disease have a good prognosis and subside without sequelae. However, diffuse multisystemic forms have a very poor prognosis. The kidney is the organ that is most often affected (in approximataly 50 % of cases). [escardio.org]
[…] boys than in girls, but occurs in less than 15% of patients. 6 The overall prognosis should be good. [nature.com]
What is the prognosis for compartment syndrome? Acute compartment syndrome is a potentially devastating condition. [medicinenet.com]
Etiology
[…] microphthalmia: a suspected warfarin embryopathy. ( 19702715 ) Downie A.C....Vote B.J. 2009 9 Fetal warfarin syndrome. ( 16856447 ) Sathienkijkanchai A....Wasant P. 2005 10 Fetal warfarin syndrome. ( 15605910 ) Hou J.W. 2004 11 Common phenotype and etiology [malacards.org]
Introduction Binder syndrome is a rare congenital anomaly with multiple etiologies and multiple associated disorders which are poorly understood because of rarity. [casereports.in]
CDP is etiologically heterogeneous. [dovepress.com]
Epidemiology
Our knowledge of potential risks to the fetus and newborn, therefore, is based on case reports, epidemiologic surveys of exposed individuals, and animal studies. [pedsinreview.aappublications.org]
[…] nerve dysfunction in a child following low-dose maternal warfarin exposure. 61 Khan AO 17896319 2007 45 Neurological sequelae of intrauterine warfarin exposure. 61 Raghav S...Reutens D 17107801 2007 46 Rheumatic and nonrheumatic valvular heart disease: epidemiology [malacards.org]
Epidemiologic measures of the course and outcome of pregnancy. Epidemiol Rev 2002; 24: 91-101. DOI:10.1093/epirev/mxf006 Garcia-Enguidanos A, Calle ME, Valero J, et al. Risk factors in miscarriage: a review. [th.schattauer.de]
Douketis, C.K.) and Clinical Epidemiology and Biostatistics (J.J., L.C., W.Y., M.G.), McMaster University, Hamilton, Ont.; the Department of Medicine (C.L., P.F., W.G.) and the Undergraduate Medical Program (S.W.), University of Toronto, Toronto; the [nejm.org]
Dai WS, Labraico JM, Stern SR (1992) Epidemiology of isotretionin exposure during pregnancy. J Am Acad Dermatol 26:599–606 PubMed CrossRef Google Scholar 118. [link.springer.com]
Pathophysiology
The pathophysiological mechanisms resulting in thrombosis in APS is incompletely understood. [clinicaladvisor.com]
with or without anti-La, rather than the type of maternal autoimmune disease, is the risk factor for the development of the disease.33 We do believe that in the cases of CPD, the maternal antibodies that cross the placenta have a major role in the pathophysiology [dovepress.com]
Prevention
Prevention[edit] Fetal warfarin syndrome is prevented by withholding prescription to pregnant women or those trying to conceive. [en.wikipedia.org]
Prevention - Fetal warfarin syndrome Not supplied. [checkorphan.org]
Aspirin Aspirin (acetyl salicylic acid) is an antiplatelet agent which is commonly used to prevent thrombosis. [cochranelibrary.com]
Coumadin, also called warfarin, is a commonly prescribed anticoagulant or blood thinner used to prevent the body from forming dangerous blood clots. [morgensternandherd.com]
References
- Vitale N, De Feo M, De Santo LS, et al. Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves. J Am Coll Cardiol 1999;33:1637–41.
- Van Driel D, Wesseling J, Rosendaal FR, et al. Growth until puberty after in utero exposure to coumarins. Am J Med Genet. 2000;95:438-43.
- Walfisch A, Koren G. The ‘warfarin window’ in pregnancy: the importance of half-life. JOGC. 2010;32:988–9.
- Hall JG, Pauli RM, Wilson K. Maternal and fetal sequelae of anticoagulant during pregnancy. Am J Med 1980;68:122-40.
- Chan Ky, Gilbert-Barness E, Tiller G. Warfarin embryopathy. Pediatr Pathol Mol Med. 2003; 22:277-83.
- Bony C, Zyka F, Tiran-Rajaofera I, et al. Warfarin fetopathy. Arch Pediatr 2002;9:705-8.
- Menger H, Lin AE, Toriello HV, et al. Vitamin K deficiency embryopathy: a phenocopy of the warfarin embryopathy due to a disorder of embryonic vitamin K metabolism. Am J Med Genet. 1997;72:129-34.
- Lee HC, Cho SY, Lee HJ, et al. Warfarin-associated fetal intracranial hemorrhage: A case report. J Korean Med Sci. 2003;18:764-7.
- Masamoto H, Uehara H, Mekaru K, et al. Warfarin-associated fetal intracranial hemorrhage in woman with mitral valve replacements: a case report. Am J Perinatol. 2009;26:597–600.
- Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Intern Med. 2000;160:191–6.
- Mason JD, Jardine A, Gibbin KP. Foetal warfarin syndrome — a complex airway problem: Case report and review of the literature. J Laryngol Otol. 1992;106:1098-9.
- Sathienkijkanchai A, Wasant P. Fetal Warfarin syndrome. J Med Assoc Thai. 2005;88(Suppl 8):S246–50.