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Fetal Warfarin Syndrome

Coumadin Syndrome

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.

Turkish
  • References [ edit ] Yurdakök, M. 2012, "Fetal and neonatal effects of anticoagulants used in pregnancy: a review", The Turkish journal of pediatrics, vol. 54, no. 3, pp. 207. a b Reid, A., Forrester, C. & Shwe, K. 2009, "Warfarin", Student BMJ, vol. 17[en.wikipedia.org]
Failure to Thrive
  • 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]
  • […] to thrive Causes - Fetal warfarin syndrome Not supplied.[checkorphan.org]
  • […] 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]
  • 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]
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]
Mouth Breathing
  • Speech and language assessment revealed high palate, mouth breathing, little nasal patency, and shortened upper lip.[ncbi.nlm.nih.gov]
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]
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]
Short Neck
  • 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, mental retardation, feeding[symptoma.com]
  • Anomalies include nasal hypoplasia, choanal atresia, laryngeal abnormalities, and upper airway obstruction, and short neck, hypoplasia of distal phalanges, brachydactyly, and short limbs.[jemds.com]
  • Such features have included abnormal calcifications and potential narrowing (stenosis) of the windpipe (trachea) and/or the larynx, which connects the throat and the trachea; an unusually short neck; abnormalities of the nails; various structural malformations[rarediseases.org]
Widely Spaced Nipples
  • spaced nipples and the Dandy-Walker malformation.[symptoma.com]
  • 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]
  • spaced nipples * Deafness * Feeding difficulty * Failure to thrive Causes - Fetal warfarin syndrome Not supplied.[checkorphan.org]
  • 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]
  • 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]
Severe Mental Retardation
  • The more extreme symptoms such as severe mental retardation, blindness and deafness occur more often when warfarin is used throughout all three trimesters. [3] Growth [ edit ] Babies born with fetal warfarin syndrome may have a below-average birth weight[en.wikipedia.org]
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]
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]

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.

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]
  • Please consult your own licensed physician regarding diagnosis and treatment of any medical condition! Please see also our disclaimer . This site complies with the HONcode standard for health information: verify here . Database updated 2019-02-19.[diseasesdatabase.com]
  • 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]

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]
  • Prognosis - Warfarin syndrome Not supplied. Treatment - Warfarin syndrome Not supplied. Resources - Warfarin syndrome Not supplied.[checkorphan.org]
  • The prognosis of the children depends on the severity of the defects. In immediate neonatal period airway management is essential. Those with hemorrhagic and CNS anomalies have poor outcomes. Long term effects are poorly understood.[jemds.com]
  • […] boys than in girls, but occurs in less than 15% of patients. 6 The overall prognosis should be good.[nature.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]
  • Binder syndrome is a rare developmental defect which has many etiologies including vitamin K deficiency which may occur following warfarin intake during first trimester. It is rare disorder occurring in less than 1 per 10,000 live births.[casereports.in]
  • […] which may lead to necrosis or death Use caution in patients with prolonged vitamin K insufficiencies Thyroid disease may increase warfarin responsiveness May impair synthesis of coagulation factors in patients with reduced liver function, regardless of etiology[reference.medscape.com]
  • Cyanosis of the digits may have several etiologies ranging from trauma to connective tissue disease, however the most common cause of blue toe syndrome is atheroembolic disease or aneurysm.[escardio.org]
  • The American College of Medical Genetics recommends testing for all males and females with mental retardation of unknown etiology Fraternal twins (dizygotic twins) Two offspring created when two separate eggs are fertilized by separate sperm during the[obfocus.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]
  • 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]
Sex distribution
Age distribution

Pathophysiology

  • The pathophysiological mechanisms resulting in thrombosis in APS is incompletely understood.[clinicaladvisor.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]

References

Article

  1. 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.
  2. 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.
  3. Walfisch A, Koren G. The ‘warfarin window’ in pregnancy: the importance of half-life. JOGC. 2010;32:988–9.
  4. Hall JG, Pauli RM, Wilson K. Maternal and fetal sequelae of anticoagulant during pregnancy. Am J Med 1980;68:122-40.
  5. Chan Ky, Gilbert-Barness E, Tiller G. Warfarin embryopathy. Pediatr Pathol Mol Med. 2003; 22:277-83.
  6. Bony C, Zyka F, Tiran-Rajaofera I, et al. Warfarin fetopathy. Arch Pediatr 2002;9:705-8.
  7. 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.
  8. Lee HC, Cho SY, Lee HJ, et al. Warfarin-associated fetal intracranial hemorrhage: A case report. J Korean Med Sci. 2003;18:764-7.
  9. 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.
  10. 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.
  11. 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.
  12. Sathienkijkanchai A, Wasant P. Fetal Warfarin syndrome. J Med Assoc Thai. 2005;88(Suppl 8):S246–50.

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Last updated: 2019-07-11 20:43