warfarin and Abnormalities--Drug-Induced

Topics: Abnormalities, Drug-Induced; Anti-Infective Agents; Anticoagulants; Biomedical Research; Cytochrome P-450 Enzyme System; Drug Eruptions; Drug Interactions; Female; Folic Acid Deficiency; Hematologic Diseases; Hemolysis; Humans; Hyperkalemia; Hypoglycemia; Hypoglycemic Agents; Immunocompromised Host; Infant, Newborn; Infant, Small for Gestational Age; Kidney; Nervous System Diseases; Pregnancy; Trimethoprim, Sulfamethoxazole Drug Combination; Warfarin

Peripartum cardiomyopathy is a life-threatening condition of unknown cause that occurs in previously healthy women during the peripartum period. It is characterized by left ventricular dysfunction and symptoms of heart failure that can arise in the last trimester of pregnancy or up to 5 months after delivery. We review its possible causes and how to recognize and manage it.

Topics: Abnormalities, Drug-Induced; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiomyopathies; Contraindications; Female; Heart Failure; Heart Transplantation; Humans; Postpartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Recurrence; Risk Factors; Ventricular Dysfunction, Left; Warfarin

Warfarin embryopathy is a well-defined manifestation of intrauterine warfarin exposure. The embryopathy phenotype as it relates to the nervous system is broad and poorly recognised. We describe an adult with neurological sequelae of fetal warfarin exposure. We review previous cases with neurological sequelae and discuss the pathogenetic mechanism in light of recent research.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Cognition Disorders; Deafness; Humans; Male; Nasal Bone; Spinal Cord Diseases; Spine; Warfarin

For haemostatic and circulatory reasons pregnancy is associated with an about 6-fold relative increase of thrombotic risk which is further raised by additional risk factors, such as history of thrombosis or acquired and hereditary thrombophilia, respectively. Recently, the thrombophilias have been revealed as risk factors for severe preeclampsia, abruptio placentae, fetal growth retardation, abortion and still birth as well. Thus, there are several situations in which the question for the need of antithrombotic medication is raised in a pregnant woman, either for therapy of acute thromboembolism or for prophylaxis of thrombosis and obstetrical complications, respectively. While acute thromboembolism has to be treated in every case, indication for prophylaxis has to be weighed in the light of the individual risk profile of the pregnant woman and the potential side effects and inconvenience of the medication. The first part of this article deals with the pregnancy related problems of coumarins, heparins and aspirin and demonstrates that the low molecular weight heparins are the anticoagulants of choice for most indications in pregnancy. The second part of this overview shows in which specific situations and how the antithrombotic medications mentioned above are used in pregnancy.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Abruptio Placentae; Administration, Oral; Adult; Anticoagulants; Aspirin; Blood Coagulation Tests; Coumarins; Female; Fetal Death; Fetal Growth Retardation; Fibrinolytic Agents; Heart Valve Prosthesis; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Disorders; Pulmonary Embolism; Risk Factors; Thrombocytopenia; Thrombophilia; Thrombosis; Warfarin

Thromboembolic complications are leading causes of both maternal and fetal morbidity and mortality. To reduce the incidence of venous thromboembolism (VTE) in pregnancy and improve outcomes, a wider understanding of the risk factors involved and better identification of women at risk of thrombosis are required. Optimal management of thromboembolic disease, both to prevent VTE and to avoid recurrence of pregnancy complications such as miscarriage, centers on the use of low-molecular-weight heparin (LMWH). LMWHs, such as enoxaparin and dalteparin, have clinical and practical advantages compared with unfractionated heparin in terms of improved safety (significantly lower incidence of osteoporosis, thrombocytopenia, and possibly allergic skin reactions) and the potential for outpatient treatment of acute VTE. However, many unanswered questions remain, including who to treat, how to treat them, and when to treat in the case of patients with thrombophilia and a history of previous pregnancy complications.

Topics: Abnormalities, Drug-Induced; Adult; Contraindications; Female; Fibrinolytic Agents; Genetic Testing; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Maternal Age; Osteoporosis; Practice Guidelines as Topic; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Pulmonary Embolism; Recurrence; Risk Factors; Thrombocytopenia; Thrombolytic Therapy; Thrombophilia; Thrombophlebitis; Warfarin

Topics: Abnormalities, Drug-Induced; Anticoagulants; Female; Fetal Diseases; Humans; Infant, Newborn; Pregnancy; Warfarin

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Calcinosis; Diagnosis, Differential; Epiphyses; Female; Fetal Diseases; Humans; Infant, Newborn; Nose; Pregnancy; Prenatal Exposure Delayed Effects; Prognosis; Syndrome; Vitamin K Deficiency; Warfarin

In general, the current recommendations for treating and prophylaxing thrombotic patients with hereditary defects are similar to those for thrombotic individuals without a defect. Determinations as to the need for long-term anticoagulation require that a clinical assessment be made regarding the relative benefit in preventing thrombotic episodes versus the risk of increased bleeding. With our newly found ability to identify genetic risk factors in a substantial fraction of patients with venous thrombosis and pulmonary embolism, it will be possible to perform rigorously designed studies to determine whether they should be managed with more prolonged or intense anticoagulation after a thrombotic event or more aggressive prophylactic regimens in high risk situations such as a total hip replacement.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Antithrombin III; Antithrombin III Deficiency; Blood Proteins; Coumarins; Disease Susceptibility; Drug Eruptions; Factor V Deficiency; Female; Fibrinolytic Agents; Genetic Predisposition to Disease; Humans; Infant, Newborn; Male; Necrosis; Pregnancy; Pregnancy Complications, Hematologic; Prevalence; Protein C; Protein S Deficiency; Puerperal Disorders; Purpura; Recurrence; Risk; Thrombolytic Therapy; Thrombosis; Warfarin

Topics: Abnormalities, Drug-Induced; Anticoagulants; Blood Coagulation Tests; Female; Heart Valve Prosthesis; Heparin; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Hematologic; Risk Factors; Thromboembolism; Warfarin

Pregnancy is associated with a prethrombotic state. Pulmonary embolism is the major cause of maternal mortality. Anticoagulant prophylaxis and therapy are therefore commonplace in pregnant women. Those with inherited and acquired thrombophilic conditions are at increased risk and special considerations arise in management. Heparin has recently become the favoured anticoagulant drug in pregnancy. Its use carries risks of osteopaenia and thrombocytopaenia, as well as haemorrhage, in the mother. Warfarin is teratogenic and may also cause haemorrhagic complications in mother and fetus. Few clinical trial data exists for guidance on optimal anticoagulant regimes during pregnancy and the puerperium and details of management will depend upon the personal preferences of patient and clinician, after due consideration of the perceived risks and benefits in the individual clinical situation.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Female; Heparin; Humans; Postpartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboembolism; Warfarin

Topics: Abnormalities, Drug-Induced; Animals; Anticonvulsants; Dose-Response Relationship, Drug; Ethanol; Female; Humans; Lithium; Maternal-Fetal Exchange; Pregnancy; Pregnancy in Diabetics; Radiotherapy; Tretinoin; Warfarin

Anticoagulant therapy during pregnancy is problematic because both heparin and oral anticoagulants can potentially produce adverse maternal and fetal effects. Reviewing the relevant literature makes it clear that heparin is safer for the fetus than are oral anticoagulants. For the prophylaxis and treatment of venous thromboembolic disease in pregnant patients, heparin is the preferred anticoagulant because its efficacy and safety are established. However, because the efficacy of heparin in preventing systemic embolism in patients with prosthetic heart valves is not established, either adjusted-dose heparin or a combination of heparin and oral anticoagulants can be used.

Topics: Abnormalities, Drug-Induced; Female; Fetal Diseases; Heart Valve Prosthesis; Heparin; Humans; Osteoporosis; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Thrombophlebitis; Warfarin

Topics: Abnormalities, Drug-Induced; Bone and Bones; Coumarins; Ear; Eye Abnormalities; Female; Humans; Infant, Newborn; Intellectual Disability; Maternal-Fetal Exchange; Nose; Pregnancy; Risk; Warfarin

Topics: Abnormalities, Drug-Induced; Dronabinol; Drug Evaluation; Ethanol; Female; Heroin; Hormones; Hot Temperature; Humans; Lysergic Acid Diethylamide; Phenytoin; Pregnancy; Registries; Teratogens; Trimethadione; Warfarin; X-Rays

Topics: Abnormalities, Drug-Induced; Adrenal Cortex Hormones; Alcoholic Beverages; Animals; Anticonvulsants; Antineoplastic Agents; Diethylstilbestrol; Estrogens; Female; Fetal Death; Fetus; Humans; Hydantoins; Iodides; Organomercury Compounds; Pregnancy; Smoking; Teratogens; Tetracycline; Thalidomide; Thiourea; Warfarin

Topics: Abnormalities, Drug-Induced; Amphetamines; Anesthetics; Animals; Anti-Anxiety Agents; Anticonvulsants; Benzodiazepines; Clomiphene; Female; Humans; Infant; Infant, Newborn; Lithium; Metronidazole; Pregnancy; Teratogens; Trimethadione; Warfarin

Topics: Abnormalities, Drug-Induced; Craniofacial Dysostosis; Dwarfism; Fingers; Gingival Diseases; Humans; Hydantoins; Mandible; Osteolysis; Syndrome; Toes; Tooth Abnormalities; Vinyl Chloride; Warfarin

In a survey of the literature the teratogenic effects of radiation and some drugs are discussed. Teratogenicity is proved for thalidomide, aminopterin, busulfan, cyclophosphamide, chlorambucil, mercaptopurin and diphenylhydantoin, trimethadione and warfarin. After the thalidomide-tragedy drug-induced malformations of the embryo are extremely rare, whereas malformations due to alcohol are rather frequent. Own experiences with more than 70 patients with alcoholembryopathy are reported. Nicotin seems not to be teratogenic, but due to nicotin the perinatal mortality is elevated. The questionable teratogenic effects of Heroin and LSD are discussed.

Topics: Abnormalities, Drug-Induced; Aminopterin; Busulfan; Chlorambucil; Cyclophosphamide; Ethanol; Germany, West; Heroin Dependence; Humans; Infant Mortality; Infant, Newborn; Lysergic Acid Diethylamide; Mercaptopurine; Nicotine; Phenytoin; Radiation Injuries; Teratogens; Thalidomide; Trimethadione; Warfarin

Topics: Abnormalities, Drug-Induced; Alcoholic Intoxication; Alcoholism; Anticonvulsants; Contraceptives, Oral; Environmental Exposure; Epilepsy; Female; Folic Acid Deficiency; Gonadal Steroid Hormones; Humans; Lysergic Acid Diethylamide; Operating Rooms; Plant Diseases; Pregnancy; Pregnancy Tests; Teratogens; Warfarin; Water Softening

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Animals; Female; Fetal Death; Heart Valve Prosthesis; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Fifty-seven pregnancies in women with antiphospholipid syndrome (APS) are presented. These were treated with s.c. enoxaparin and low dose aspirin. In fourteen pregnancies warfarin was prescribed between weeks 15-34 (warfarin group). The decision to switch to warfarin depended on a morbidity score, and the patient's consent. Neither teratogenicity nor significant maternal, fetal or neonatal hemorrhage was observed. Despite the higher pretreatment morbidity score of the warfarin group, the live birth rate was high in both groups: 86% in the warfarin group and 87% in the non-warfarin group. There was no significant difference in week of delivery, birth weight, or incidence of thrombosis between the groups. The study demonstrates the efficacy and safety of anticoagulants during pregnancy. The use of LMWH in pregnant women with APS not being moot, warfarin might be justified in selected patients.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Autoimmune Diseases; Enoxaparin; Female; Hemorrhage; Humans; Infant, Newborn; Lupus Erythematosus, Systemic; Nervous System Diseases; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy, Multiple; Safety; Thrombosis; Warfarin

Topics: Abnormalities, Drug-Induced; Humans; Infant, Newborn; Nasal Bone; Warfarin

Anticoagulant therapy is commonly indicated during pregnancy to prevent thrombosis and prevention of prosthetic heart valve-associated thromboembolic events. Warfarin is a synthetic anticoagulant with low molecular weight and can cross the placenta resulting in congenital abnormalities termed fetal warfarin syndrome. This paper highlights the case of an 8-year-old boy with warfarin embryopathy. It highlights the extraoral and intraoral findings of the case along with the cephalometric analysis and provides insight into the phenotypic variations among the different cases reported in the literature.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Child; Female; Heart Valve Prosthesis; Humans; Male; Nasal Bone; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Vitamin K antagonists (VKA) are not recommended during pregnancy because warfarin (a first-generation VKA) is associated with a malformation syndrome "the fetal warfarin syndrome" (FWS). VKA are also used for rodent management worldwide. Recently, the Committee for Risk Assessment responsible for the European chemical legislation for advances on the safe use of chemicals had classed 8 anticoagulant used as rodenticides in the reprotoxic category 1A or 1B. This classification emerges from a read-across prediction of toxicity considering the warfarin malformation syndrome. Herein, our study explores the teratogenicity of warfarin at the human therapeutic dose and that of bromadiolone, a second-generation anticoagulant rodenticide. Using a rat model, our study demonstrates that warfarin used at the therapeutic dose is able to induce teratogenicity, while in the same conditions bromadiolone does not induce any teratogenic effect, challenging the classification of all VKA as reprotoxic molecules.

Topics: 4-Hydroxycoumarins; Abnormalities, Drug-Induced; Animals; Anticoagulants; Bone and Bones; Female; Male; Maternal-Fetal Exchange; Nose; Pregnancy; Rats, Sprague-Dawley; Rodenticides; Teratogens; Vitamin K; Warfarin

Warfarin is the most worldwide used anticoagulant drug and rodenticide. Since it crosses placental barrier it can induce warfarin embryopathy (WE), a fetal mortality in neonates characterized by skeletal deformities in addition to brain hemorrhages. Although the effects of warfarin exposure in aquatic off target species were already described, the particular molecular toxicological mechanisms during early development are still unclear. Here, we used zebrafish (Danio rerio) to describe and compare the developmental effects of warfarin exposure (0, 15.13, 75.68 and 378.43 mM) on two distinct early developmental phases (embryos and eleuthero-embryos). Although exposure to both developmental phases induced fish mortality, only embryos exposed to the highest warfarin level exhibited features mimicking mammalian WE, e.g. high mortality, higher incidence of hemorrhages and altered skeletal development, among other effects. To gain insights into the toxic mechanisms underlying warfarin exposure, the transcriptome of embryos exposed to warfarin was explored through RNA-Seq and compared to that of control embryos. 766 differentially expressed (564 up- and 202 down-regulated) genes were identified. Gene Ontology analysis revealed particular cellular components (cytoplasm, extracellular matrix, lysosome and vacuole), biological processes (mainly amino acid and lipid metabolism and response to stimulus) and pathways (oxidative stress response and apoptosis signaling pathways) being significantly overrepresented in zebrafish embryos upon warfarin exposure. Protein-protein interaction further evidenced an altered redox system, blood coagulation and vasculogenesis, visual phototransduction and collagen formation upon warfarin exposure. The present study not only describes for the first time the WE in zebrafish, it provides new insights for a better risk assessment, and highlights the need for programming the rat eradication actions outside the fish spawning season to avoid an impact on off target fish community. The urge for the development of more species-specific anticoagulants for rodent pest control is also highlighted.

Topics: Abnormalities, Drug-Induced; Animals; Anticoagulants; Disease Models, Animal; Embryo, Nonmammalian; Humans; Nasal Bone; Oxidative Stress; Rodenticides; Transcriptome; Warfarin; Water Pollutants, Chemical; Zebrafish

Congenital abnormalities and pregnancy losses due to the teratogenic effects of warfarin are prevalent among the South African population. These are potentially preventable if the challenges and barriers faced by at-risk women are understood and addressed effectively.. To determine the practice, knowledge and attitudes regarding the teratogenic risks experienced by women administered warfarin.. A descriptive study was performed. Quantitative data were collected through a researcher-administered questionnaire. The target population comprised 101 women of reproductive age who received warfarin treatment and attended a single tertiary-level anticoagulation clinic.. Patient-related challenges identified in this study are: language barriers, poor understanding of basic terminology and mathematics, poor contraceptive and family planning practices, lack of knowledge regarding the risks of warfarin in pregnancy and passive attitudes towards information attainment.. Interventions are necessary to address the challenges in such settings. These include increased awareness of the teratogenic potential of specific chronic medications among healthcare providers, patients and the public. Standardised management protocols for women of reproductive age initiated on teratogenic medications should be implemented, including contraceptive and family planning discussions at follow-up visits. Improvement of the counselling skills of healthcare providers and the availability of translators or healthcare providers fluent in local languages could assist in risk reduction.

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Anticoagulants; Attitude to Health; Communication Barriers; Contraception Behavior; Embolism; Family Planning Services; Female; Health Knowledge, Attitudes, Practice; Heart Valve Prosthesis Implantation; Humans; Middle Aged; Patient Education as Topic; Pregnancy; Venous Thrombosis; Warfarin; Young Adult

Fetuses exposed to warfarin during pregnancy are at an increased risk of developing an embryopathy known as fetal warfarin syndrome or warfarin embryopathy. The most consistent anomalies are nasal hypoplasia and stippling of vertebrae or bony epiphyses. Management of pregnant patients on anticoagulation is challenging. Current guidelines suggest the use of warfarin if the therapeutic dose is ≤5 mg/day. We report the case of a newborn with signs of warfarin embryopathy born from a mother anticoagulated with warfarin due to mechanical mitral and aortic heart valves. Warfarin was required at the dose of 5 mg/day and was withheld without medical advice between weeks 8 and 10 with no other anticoagulation. The newborn presented with skeletal abnormalities and a ventricular septal defect that have not required specific treatment during the first year of life. Low-dose warfarin is associated with a lower risk of warfarin-related fetopathy but the risk of embryopathy seems unchanged.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Congenital Abnormalities; Female; Heart Valve Prosthesis; Humans; Infant, Newborn; Male; Nasal Bone; Nasal Cartilages; Pregnancy; Pregnancy Complications, Cardiovascular; Treatment Outcome; Warfarin

Chondrodysplasia punctata is abnormal calcification in the cartilage of developing bones and has been seen in association with deranged vitamin K metabolism. Warfarin, an oral anticoagulant acting on vitamin K dependent clotting factors is known to cause chondrodysplasia punctata. Despite the knowledge of the condition the management of patients with prosthetic heart valves might require use of the drug for anticoagulation. Here, we present a case of a fetal warfarin syndrome in a second born child of a 27 year lady under warfarin for prosthetic heart valve. The pregnancy was complicated by polyhydramnios in third trimester and terminated at term by normal vaginal delivery. The baby was well, except for facial dysmorphism in the form of depressed nasal bridge, narrow nares and suspected left choanal atresia. Radiograph revealed stippled ephiphysis of vertebra, femora and humera supporting diagnosis of fetal warfarin syndrome. The baby did not develop any perinatal complication and was discharged home.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Chondrodysplasia Punctata; Female; Heart Valve Prosthesis; Humans; Infant, Newborn; Nasal Bone; Nepal; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Exposure to teratogenic drugs during pregnancy is associated with a wide range of embryo-fetal anomalies and sometimes results in recurrent and recognizable patterns of malformations; however, the comprehension of the mechanisms underlying the pathogenesis of drug-induced birth defects is difficult, since teratogenesis is a multifactorial process which is always the result of a complex interaction between several environmental factors and the genetic background of both the mother and the fetus. Animal models have been extensively used to assess the teratogenic potential of pharmacological agents and to study their teratogenic mechanisms; however, a still open issue concerns how the information gained through animal models can be translated to humans. Instead, significant information can be obtained by the identification and analysis of human genetic syndromes characterized by clinical features overlapping with those observed in drug-induced embryopathies. Until now, genetic phenocopies have been reported for the embryopathies/fetopathies associated with prenatal exposure to warfarin, leflunomide, mycophenolate mofetil, fluconazole, thalidomide and ACE inhibitors. In most cases, genetic phenocopies are caused by mutations in genes encoding for the main targets of teratogens or for proteins belonging to the same molecular pathways. The aim of this paper is to review the proposed teratogenic mechanisms of these drugs, by the analysis of human monogenic disorders and their molecular pathogenesis.

Topics: Abnormalities, Drug-Induced; Angiotensin-Converting Enzyme Inhibitors; Animals; Female; Fetal Diseases; Fetus; Fluconazole; Humans; Isoxazoles; Leflunomide; Mutation; Mycophenolic Acid; Phenotype; Pregnancy; Teratogenesis; Teratogens; Thalidomide; Warfarin

Fetal exposure to maternal ingestion of warfarin is known to produce certain dysmorphic features in the neonate, known as fetal warfarin syndrome (FWS). There is a general consensus that maternal intake of warfarin at a daily dose of 5 mg or less is safe both for the infant and the mother.. We report four cases of FWS born to mothers with rheumatic heart disease on warfarin prophylaxis during pregnancy at a dose less than 5 mg/day.. Along with typical facial features of FWS and multiple epiphyseal stippling in skeletal x-ray, Case 1 had Dandy-Walker malformation and Case 2 had laryngo-tracheomalacia and patent ductus arteriosus.. We emphasize the need for optimizing the choice and dosage schedule of anticoagulants during pregnancy, least harmful for the mother and her developing fetus.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adult; Anticoagulants; Dandy-Walker Syndrome; Ductus Arteriosus, Patent; Female; Heart Valve Prosthesis; Humans; Nasal Bone; Pregnancy; Prenatal Exposure Delayed Effects; Rheumatic Heart Disease; Warfarin

Warfarin is a synthetic oral anticoagulant that crosses the placenta and can lead to a number of congenital abnormalities known as fetal warfarin syndrome. Our aim is to report on the follow-up from birth to age 8 years of a patient with fetal warfarin syndrome. He presented significant respiratory dysfunction, as well as dental and speech and language complications. The patient was the second child of a mother who took warfarin during pregnancy due to a metallic heart valve. The patient had respiratory dysfunction at birth. On physical examination, he had a hypoplastic nose, pectus excavatum, and clubbing of the fingers. Nasal fibrobronchoscopy showed upper airway obstruction due to narrowing of the nasal cavities. He underwent surgical correction with Max Pereira graft, zetaplasty, and osteotomies for the piriform aperture. At dental evaluation, he had caries and delayed eruption of the upper incisors. Speech and language assessment revealed high palate, mouth breathing, little nasal patency, and shortened upper lip. Auditory long latency and cognitive-related potential to auditory stimuli demonstrated functional changes in the cortical auditory pathways. We believe that the frequency of certain findings observed in our patient may be higher in fetal warfarin syndrome than is appreciated, since a significant number result in abortions, stillbirths, or children evaluated in the first year of life without a follow-up. Thus, a multidisciplinary approach and long-term monitoring of these patients may be necessary.

Topics: Abnormalities, Drug-Induced; Auditory Perceptual Disorders; Child; Female; Fetus; Follow-Up Studies; Humans; Male; Mothers; Nasal Bone; Nasal Obstruction; Osteotomy; Pregnancy; Prenatal Exposure Delayed Effects; Tooth Abnormalities; Warfarin

Topics: Abnormalities, Drug-Induced; Atlanto-Axial Joint; Humans; Joint Dislocations; Male; Nasal Bone; Warfarin

Neonatal chondrodysplasia punctata (CDP) is characterized by epiphyseal stippling and midfacial hypoplasia. CDP is usually inherited, but can be acquired because of maternal vitamin K deficiency. We describe an infant with CDP born to a teenager with sickle cell anemia and transfusional iron overload. The mother had severe liver fibrosis, elevated liver iron concentration (34 mg Fe/g), and coagulopathy, but no gestational use of warfarin. Fetal abnormalities were attributed to vitamin K deficiency secondary to liver dysfunction from iron toxicity. Treatment of iron overload among women with sickle cell anemia of childbearing potential is important to avoid possible CDP in newborns.

Topics: Abnormalities, Drug-Induced; Adolescent; Anemia, Sickle Cell; Chondrodysplasia Punctata; Female; Humans; Infant, Newborn; Iron Overload; Liver Diseases; Male; Nasal Bone; Pregnancy; Pregnancy Complications; Transfusion Reaction; Vitamin K Deficiency; Warfarin

There is high incidence of rheumatic valvular heart disease in developing countries like Bangladesh, for which large number of young females undergo valve replacement with mechanical prosthetic heart valve. Pregnancy with mechanical heart valve carries risk of warfarin embryopathy and increased incidence of maternal thrombo-embolism. We had successful outcome of pregnancy of a patient with mechanical prosthetic heart valve with home heparin therapy.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Female; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Mitral Valve; Mitral Valve Stenosis; Nasal Bone; Pregnancy; Pregnancy Complications, Cardiovascular; Self Administration; Warfarin

Di Sala syndrome or fetal warfarin syndrome/fetal warfarin embryopathy is a rare condition as result of fetal exposure due to maternal ingestion of warfarin during pregnancy. The authors report here a male infant with this condition whose mother was suffering from rheumatic mitral valvular heart disease for which she underwent prosthetic mitral valvular replacement surgery and put on injectable long acting penicillin and oral low-molecular weight anticoagulant drug (warfarin) for life long. The patient presented with facial dysmorphism, pectus excavatum, stippled epiphyses dolichocephaly, brachydactyly, polydactyly short neck and growth retardation. Shortened fourth metacarpal bones were also noted in this case which was not yet reported in literatures, to the best of our knowledge.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Anticoagulants; Diagnosis, Differential; Female; Humans; Infant; Male; Pregnancy; Prenatal Exposure Delayed Effects; Syndrome; Warfarin

Cardiac disease in pregnancy is a common problem in under-resourced countries and a significant cause of maternal morbidity and mortality. A large proportion of patients with cardiac disease have prosthetic mechanical heart valve replacements, warranting prophylactic anticoagulation.. To evaluate obstetric outcomes in women with prosthetic heart valves in an under-resourced country.. A retrospective chart review was performed of 61 pregnant patients with prosthetic valve prostheses referred to our tertiary hospital over a five-year period.. Sixty-one (6%) of 1 021 pregnant women with A diagnosis of cardiac disease had prosthetic heart valves. Fifty-nine had mechanical valves and were on prophylactic anticoagulation therapy, three had stopped their medication prior to pregnancy and two had bioprosthetic valves. There were forty-one (67%) live births, two (3%) early neonatal deaths, 12 (20%) miscarriages and six (10%) stillbirths. Maternal complications included mitral valve thrombosis (n = 4), atrial fibrillation (n = 8), infective endocarditis (n = 6), caesarean section wound haematomas (n = 7), broad ligament haematoma (n = 1) and warfarin embryopathy (n = 4). Haemorrhagic complications occurred in five patients and all five required blood transfusions.. Prophylactic anticoagulation with warfarin in patients with mechanical heart valve prostheses was associated with high rates of maternal and neonatal complications, including significant foetal wastage in the first and early second trimesters of pregnancy. Health professionals providing care for pregnant women with prosthetic heart valves must consistently advise on family planning matters, adherence to anticoagulation regimes and consider the use of prophylactic anticoagulant regimens other than warfarin, particularly during the first trimester of pregnancy.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Clinical Audit; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Incidence; Middle Aged; Nasal Bone; Postoperative Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Retrospective Studies; South Africa; Tertiary Care Centers; Time Factors; Warfarin; Young Adult

A case of a baby born preterm with an antenatal diagnosis of aortic coarctation for which prostin was electively started at birth. The baby was found to be profoundly anaemic with no clear obstetric cause. Features consistent with antenatal intracerebral haemorrhage were noted on cranial ultrasonography in the context of severe coagulopathy, prompting investigations which confirmed fetal-maternal haemorrhage. It transpired that, following aortic and mitral valve replacements, the mother was anticoagulated with warfarin at conception, having misunderstood her cardiologist's advice that: 'you cannot get pregnant whilst on warfarin'. Following conversion to low molecular weight heparin, she suffered a stroke, thus warfarin was restarted, with an international normalised ratio of 3-4.7 during pregnancy. Following transfer to the paediatric intensive care unit, fetal warfarin syndrome was diagnosed. The coagulopathy and anaemia were corrected and aortic coarctation was excluded. The baby returned to the neonatal intensive care unit for ongoing care and was discharged home in good condition around his due date. At the present time, there is no clinically overt neurological deficit.

Topics: Abnormalities, Drug-Induced; Anemia; Anticoagulants; Aortic Coarctation; Blood Coagulation; Blood Coagulation Disorders; Female; Fetal Diseases; Heart Valves; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Infant, Premature; Maternal-Fetal Exchange; Nasal Bone; Postoperative Complications; Pregnancy; Premature Birth; Stroke; Warfarin

Warfarin, which is used for anticoagulant therapy, rarely produces congenital warfarin syndrome characterized with hypoplastic nose, stippled epiphyses, and skeletal abnormalities when ingested during pregnancy. Here, we present a male infant, whose mother was treated with warfarin because of a prosthetic heart valve replacement after rheumatic heart disease, with signs of warfarin embryopathy. The mother's first pregnancy at 12 weeks gestation resulted in abortus due to warfarin toxicity. Subsequently, she delivered two healthy girls after her treatment had changed to low molecular heparin during pregnancy periods. We want to emphasize that risk-benefit ratio should be well weighed by both obstetricians and cardiologists when considering warfarin therapy for a woman at childbearing age.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Anticoagulants; Female; Heart Valve Prosthesis; Humans; Infant, Newborn; Male; Mothers; Nasal Bone; Pregnancy; Prenatal Exposure Delayed Effects; Warfarin

Fetal warfarin syndrome (warfarin embryopathy) is a consequence of maternal ingestion of warfarin during pregnancy. Warfarin fetotoxicity comprises wide range of manifestations including dysmorphology in neonate with characteristic classical features of nasal hypoplasia and stippling of epiphyses.. Here we present a case of a neonate whose mother was on unsupervised warfarin prophylaxis throughout pregnancy. A brief review of literature with suitable options for anticoagulation during pregnancy is discussed.. The final consensus over LMWH and warfarin in the first trimester is yet to be finalised. The treatment of warfarin embryopathy is symptomatic. Long term sequels in survivors are still not known.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Female; Humans; Infant, Newborn; Infant, Small for Gestational Age; Male; Osteochondrodysplasias; Pregnancy; Vitamin K; Warfarin

Topics: Abnormalities, Drug-Induced; Anticoagulants; Female; Humans; Imaging, Three-Dimensional; Infant, Newborn; Male; Nasal Bone; Pregnancy; Respiratory Distress Syndrome, Newborn; Respiratory Tract Infections; Tracheotomy; Ultrasonography, Prenatal; Warfarin

During the period 1991-2007, autopsy was undertaken in 13 fetuses with warfarin embryopathy. Pregnancy data and radiographic babygrams were available in each instance. Gestational age ranged from 17 to 37 weeks. Eleven of the fetuses had the characteristic nasal hypoplasia, but only three had radiological epiphyseal stippling. Cerebral hemorrhage was a major feature of autopsy in 8 of the fetuses, and it is evident that bleeding is a significant factor in the pathogenesis of warfarin embryopathy. A wide variety of additional visceral manifestations which were observed at autopsy have been tabulated. There was no obvious correlation between maternal or gestational age and the presence and severity of any specific embryopathic feature. No information was available concerning the dose and timing of warfarin administration in this series.

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Anticoagulants; Autopsy; Cerebral Hemorrhage; Chondrodysplasia Punctata; Female; Fetal Development; Heart Valve Diseases; Humans; Hyperplasia; Nose; Pregnancy; Retrospective Studies; Warfarin; Young Adult

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Corneal Opacity; Female; Fetal Development; Fetal Diseases; Humans; Microphthalmos; Pregnancy; Pulmonary Embolism; Warfarin

Guidelines concerning the prevention and treatment of pregnancy-associated venous thromboembolism (VTE) have been elaborated by the American College of Chest Physicians and published in Chest in 2008. In this review, they have been compared with European guidelines and discussed taking into account the papers published since 2008.Most recommendations are of low grade of evidence because randomized studies are lacking during pregnancy and many reflect guidelines proposed by experts. The decisions on the most appropriate prophylaxis, dose to be administered and moment of pregnancy for starting prophylaxis are often decided case by case after careful assessment of the risk of pregnancy-associated VTE, on one hand, and the risk for the mother, on the other.Risk factors (age >or= 35, obesity, history of VTE with or without sequellae, in vitro fertilization)or thrombophilia have to be taken into account. Scores have been proposed to improve standardisation and evaluation of the risk of VTE and they should be validated.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Benzimidazoles; Blood Loss, Surgical; Cesarean Section; Contraindications; Dabigatran; Europe; Evidence-Based Medicine; Female; Fetus; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Morpholines; Polysaccharides; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders; Pyridines; Rivaroxaban; Societies, Medical; Thiophenes; Thrombophilia; United States; Uterine Hemorrhage; Venous Thromboembolism; Warfarin

Topics: Abnormalities, Drug-Induced; Anticoagulants; Cerebrum; Cesarean Section; Female; Heart Valve Prosthesis; Humans; Infant, Newborn; Intracranial Hemorrhages; Middle Aged; Pregnancy; Pregnancy Complications, Cardiovascular; Ultrasonography, Prenatal; Warfarin

Because the embryopathy associated with maternal warfarin use seems dose-dependent, some physicians advocate low-dose warfarin for pregnant women requiring anticoagulation. The current case, however, highlights that optic nerve dysfunction (as well as other signs of warfarin embryopathy) can occur after low-dose maternal warfarin exposure.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Dose-Response Relationship, Drug; Face; Female; Humans; Infant; Nails, Malformed; Optic Nerve Diseases; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Venous Thrombosis; Warfarin

Vitamin K antagonists (VKA) are known to act as teratogens; however, there is still uncertainty about the relative risk for birth defects and the most sensitive period. In a multi-centre (n = 12), observational, prospective study we compared 666 pregnant women exposed to phenprocoumon (n = 280), acenocoumarol (n = 226), fluindione (n = 99), warfarin (n = 63) and phenindione (n = 2) to a non-exposed control group (n = 1,094). Data were collected by institutes collaborating in the European Network of Teratology Information Services (ENTIS) during individual risk counselling between 1988 and 2004. Main outcome measures were coumarin embryopathy and other birth defects, miscarriage rate, birth-weight, and prematurity. The rate of major birth defects after 1st trimester exposure was significantly increased (OR 3.86, 95% CI 1.86-8.00). However, there were only two coumarin embryopathies (0.6%; both phenprocoumon). Prematurity was more frequent (16.0% vs. 7.6%, OR 2.61, 95% CI 1.76-3.86), mean gestational age at delivery (37.9 vs.39.4, p<0.001), and mean birth weight of term infants (3,166 g vs. 3,411 g; p < 0.001) were lower compared to the controls. Using the methodology of survival analysis, miscarriage rate reached 42% vs. 14% (hazard ratio 3.36; 95% CI 2.28-4.93). In conclusion, use of VKA during pregnancy increases the risk of structural defects and other adverse pregnancy outcomes. The risk for coumarin embryopathy is, however, very small, in particular when therapy during the 1(st) trimester did not take place later than week 8 after the 1(st) day of the last menstrual period. Therefore, elective termination of a wanted pregnancy is not recommended if (inadvertent) exposure took place in early pregnancy. Close follow-up by the obstetrician including level II ultrasound should be recommended in any case of VKA exposure during pregnancy.

Topics: Abnormalities, Drug-Induced; Abortion, Induced; Abortion, Spontaneous; Acenocoumarol; Adverse Drug Reaction Reporting Systems; Anticoagulants; Birth Weight; Female; Fetal Diseases; Gestational Age; Humans; Phenindione; Phenprocoumon; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Premature Birth; Prospective Studies; Vitamin K; Warfarin

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Female; Humans; Infant, Newborn; Maternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Warfarin

Fetuses exposed to Warfarin in the first trimester of pregnancy have an increased risk of embryopathy which consists of nasal hypoplasia and stippled epiphyses, known as fetal warfarin syndrome or warfarin embryopathy. We herein report a first case of an infant with fetal warfarin syndrome in Thailand. The patient was an offspring of a 34-year-old mother with history of SLE and arterial embolism for several years. She had an unplanned pregnancy while taking warfarin. The patient developed difficulty breathing in the first few hours after birth from severe nasal hypoplasia. 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.

Topics: Abnormalities, Drug-Induced; Fetal Diseases; Humans; Infant, Newborn; Male; Syndrome; Warfarin

Fetal warfarin syndrome (FWS) or warfarin (coumadin) embryopathy is a rare condition as a result of fetal exposure to maternal ingestion of warfarin during pregnancy. A male infant, whose mother was treated with the anticoagulant (warfarin) because of a mechanical heart valve replacement after rheumatic heart disease, presented with signs of warfarin embryopathy. The facial dysmorphism included hypoplasia of nasal bridge, laryngomalacia, pectus carinatum, congenital heart defects (atrial septal defect and patent ductus arteriosus), ventriculomegaly, stippled epiphyses, telebrachydactyly, and growth retardation. The pathogenesis and management of FWS are discussed.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Anticoagulants; Female; Growth and Development; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Infant, Premature; Male; Maternal Exposure; Nose; Pregnancy; Prenatal Exposure Delayed Effects; Warfarin

The aim of this study was to de the role of the nasal septum in embryonic facial development.. Nasal septal growth and facial development were examined in sagittally-sectioned 6-9 week human foetuses and compared to previously published data for later prenatal periods. To complement this data a cephalometric study of a child with untreated warfarin embryopathy was undertaken since a previous study in rats had shown warfarin exposure interferes with septal growth.. The results showed that prenatal septal growth was maximal during the 6-9 week period and resulted in the establishment of a facial profile that was maintained until birth. This critical of growth corresponds to the period of warfarin exposure of the human foetus that results warfarin embryopathy. The cephalometric examination of a child with untreated warfarin embryopathy showed a combination of short anterior cranial base and a short maxilla had contributed to a significant retrusion of the maxilla suggestive of failure of the midface to devel the 6-9 week period.. These findings would support the hypothesis that the nasal septum plays an active role in embryonic midfacial development.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Cephalometry; Child; Craniofacial Abnormalities; Face; Fetal Development; Humans; Male; Maxilla; Nasal Septum; Skull Base; Warfarin

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Anticoagulants; Bone Transplantation; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Maxillofacial Development; Nose; Postoperative Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Reoperation; Rhinoplasty; Thrombophlebitis; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Abnormalities, Drug-Induced; Anticoagulants; Enoxaparin; Female; Heart Valve Prosthesis; Humans; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Safety; Thrombosis; Warfarin

We report a case of warfarin embryopathy. This disease affects more than 6% of fetuses exposed in utero to a vitamin K antagonist.. A child whose mother was treated with acenocoumarol because of a mechanical heart valve presented with signs of warfarin embryopathy. He showed chondrodysplasia punctata with telebrachydactyly, facial dysmorphism with nasal hypoplasia, a cataract, and a bilateral pyeloureteral junction syndrome.. Characteristics of this drug induced embryopathy are reminded, while bearing in mind the conflict of interests between the mother and the fetus. The mechanisms of this embryopathy are debated in light of the recent knowledge concerning fetal metabolism of vitamin K.

Topics: Abnormalities, Drug-Induced; Acenocoumarol; Adult; Age Factors; Anticoagulants; Child, Preschool; Chondrodysplasia Punctata; Female; Fetus; Follow-Up Studies; Heart Valve Prosthesis; Humans; Infant; Male; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Exposure Delayed Effects; Time Factors; Warfarin

To assess the perception of the teratogenic risk of common medication by professionals and lay people.. A visual-analogue scale was used to measure the perceived percentage of mothers who will deliver a child with a malformation, including those exposed to a list of drugs. Fifteen general practitioners, 10 gynaecologists, 106 pre-clinical students, 150 students in their clinical training, 81 pregnant women and 63 non-pregnant women were interviewed.. The perception of the teratogenic risk related to medication used in pregnancy was higher than the recognised risk in all groups, and for all drugs. The risk associated with safe medications was perceived to be higher by non-pregnant women as compared with the pregnant women. Pregnant women perceived the medication associated risk to be higher than physicians did for all drugs included in the questionnaire.. The high and unrealistic perception of teratogenic risk amongst women and health professionals may lead to abortions of otherwise wanted and healthy children.

Topics: Abnormalities, Drug-Induced; Chi-Square Distribution; Drug-Related Side Effects and Adverse Reactions; Erythromycin; Female; Health Knowledge, Attitudes, Practice; Humans; Physicians; Pregnancy; Risk Factors; Students, Medical; Teratogens; Warfarin

Pregnancy associated with primary pulmonary hypertension is an uncommon observation, with maternal mortality > 50%. Experience treating this condition is limited. Past reports have emphasized the need for pregnancy termination. In the last few years there has been considerable interest in long-term intravenous use of epoprostenol (prostacyclin) in patients with primary pulmonary hypertension.. A woman with severe primary pulmonary hypertension who was on long-term epoprostenol therapy became pregnant with twins and was treated with high doses of epoprostenol and nitric oxide during delivery and the postpartum period. She was well six months later on continuous epoprostenol therapy. The one viable infant was alive and still hospitalized at this writing.. Epoprostenol therapy may be continued during pregnancy in patients with severe primary pulmonary hypertension for long-term pulmonary vasodilatation.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Antihypertensive Agents; Bronchodilator Agents; Epoprostenol; Face; Female; Humans; Hydrocephalus; Hypertension, Pulmonary; Nitric Oxide; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy, Multiple; Syndrome; Twins; Warfarin

Topics: Abnormalities, Drug-Induced; Animals; Anticoagulants; Bioprosthesis; Cattle; Coumarins; Female; Heart Valve Prosthesis; Heparin; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Factors; Warfarin

The purpose of this study was to assess the incidence of warfarin fetal complications and whether they are dose-dependent.. Gravid patients with mechanical heart valves require long-term anticoagulant therapy. Controversy exists concerning the appropriate treatment of these patients.. Forty-three women on warfarin carrying out 58 pregnancies were studied. For each patient with full-term pregnancy a caesarian section was scheduled for the 38th week during brief warfarin discontinuation. Maternal and fetal complications were evaluated. Fetal complications were divided according to the warfarin dosage < or = 5 mg and > 5 mg necessary to keep an international normalized ratio (INR) of 2.5 to 3.5, and analyzed subsequently.. A total of 58 pregnancies were observed: 31 healthy babies (30 full term, 1 premature) and 27 fetal complications (22 spontaneous abortions, 2 warfarin embryopathies, 1 stillbirth, 1 ventricular septal defect, 1 growth retardation) were recorded. Two maternal valve thromboses occurred. No fetal or maternal bleeding was observed during caesarian sections or premature vaginal delivery. Patients whose warfarin doses during pregnancy were > 5 mg had 22 fetal complications, whereas those taking a dose < or = 5 mg had only five fetal complications (p = 0.0001). For an increase of the warfarin dose there was a substantially increased probability of fetal complications (p < 0.0001; p < 0.7316).. There is a close dependency between warfarin dosage and fetal complications. Patients on warfarin anticoagulation may be delivered by planned caesarian section at the 38th week while briefly interrupting anticoagulation.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Cesarean Section; Dose-Response Relationship, Drug; Female; Fetal Death; Heart Valve Prosthesis Implantation; Humans; Infant, Newborn; International Normalized Ratio; Male; Pregnancy; Pregnancy Complications, Cardiovascular; Prosthesis Failure; Thrombosis; Warfarin

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Chondrodysplasia Punctata; Female; Femur; Fetal Death; Fetal Growth Retardation; Gestational Age; Humans; Male; Nose; Pregnancy; Syndrome; Ultrasonography, Prenatal; Warfarin

Topics: Abnormalities, Drug-Induced; Anticoagulants; Canada; Documentation; Female; Humans; Infant, Newborn; Malpractice; Patient Education as Topic; Pregnancy; Referral and Consultation; Warfarin

A patient with warfarin embryopathy developed progressive cervical spinal myelopathy owing to bony cervical spinal damage. While there are several descriptions of warfarin embryopathy, the long-term complication of cervical spinal instability has not been reported. This cervical instability may, as in our patient, cause severe neurological dysfunction or even sudden death; therefore, it is important that pediatric radiologists should be alert to this condition.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Cervical Vertebrae; Chondrodysplasia Punctata; Female; Follow-Up Studies; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications, Hematologic; Pulmonary Embolism; Radiography; Spinal Cord Compression; Warfarin

Topics: Abnormalities, Drug-Induced; Anticoagulants; Female; Fetal Death; Heart Valve Prosthesis; Humans; Pregnancy; Pregnancy Complications, Hematologic; Warfarin

Topics: Abnormalities, Drug-Induced; Acute Disease; Aged; Aged, 80 and over; Aging; Anticoagulants; Chronic Disease; Drug Hypersensitivity; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Forecasting; Gene Expression; Genetic Predisposition to Disease; Humans; Malignant Hyperthermia; Pharmacogenetics; Preventive Dentistry; Preventive Medicine; Risk; Treatment Outcome; Warfarin

Three unrelated infants presented with radiographic punctate calcifications, nasal hypoplasia, and abnormalities of the spine. Additional anomalies included cupped ears in 2 patients and one each with Dandy-Walker malformation with hydrocephaly, congenital cataracts, and peripheral pulmonary artery stenosis. The mothers of these 3 patients had chronic conditions associated with intestinal malabsorption requiring total parenteral nutrition for varying periods of time. The underlying causes of malabsorption were celiac disease, short bowel syndrome secondary to surgical resection, and jejuno-ileal bypass, respectively. Bleeding diathesis occurred in one mother requiring vitamin K supplementation during the second and third trimesters of pregnancy. We speculate that the chondrodysplasia punctata and other abnormalities in these children were caused by an acquired maternal vitamin K deficiency manifested during early pregnancy. However, the involvement of other vitamin deficiencies cannot be excluded. Thus, vitamin K deficiency of the embryo secondary to maternal malabsorption appears to be a third vitamin K-related mechanism leading to chondrodysplasia punctata in addition to warfarin embryopathy and epoxide reductase deficiency (pseudo-warfarin embryopathy).

Topics: Abnormalities, Drug-Induced; Anticoagulants; Child, Preschool; Chondrodysplasia Punctata; Female; Fetal Diseases; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Malabsorption Syndromes; Pregnancy; Pregnancy Complications; Radiography; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Abnormalities, Drug-Induced; Anticoagulants; Contraindications; Female; Heart Valve Prosthesis; Heparin; Humans; Pregnancy; Pregnancy Complications; Thromboembolism; Warfarin

X-linked recessive chondrodysplasia punctata (CDPX) is a congenital defect of bone and cartilage development characterized by aberrant bone mineralization, severe underdevelopment of nasal cartilage, and distal phalangeal hypoplasia. A virtually identical phenotype is observed in the warfarin embryopathy, which is due to the teratogenic effects of coumarin derivatives during pregnancy. We have cloned the genomic region within Xp22.3 where the CDPX gene has been assigned and isolated three adjacent genes showing highly significant homology to the sulfatase gene family. Point mutations in one of these genes were identified in five patients with CDPX. Expression of this gene in COS cells resulted in a heat-labile arylsulfatase activity that is inhibited by warfarin. A deficiency of a heat-labile arylsulfatase activity was demonstrated in patients with deletions spanning the CDPX region. These data indicate that CDPX is caused by an inherited deficiency of a novel sulfatase and suggest that warfarin embryopathy might involve drug-induced inhibition of the same enzyme.

Topics: Abnormalities, Drug-Induced; Amino Acid Sequence; Arylsulfatases; Base Sequence; Cell Line; Chondrodysplasia Punctata; Chromosome Mapping; Cloning, Molecular; Fibroblasts; Gene Expression Regulation, Enzymologic; Humans; Male; Molecular Sequence Data; Multigene Family; Organ Specificity; Point Mutation; RNA, Messenger; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Warfarin; X Chromosome

Topics: Abnormalities, Drug-Induced; Aspirin; Bioprosthesis; Embryo, Mammalian; Female; Heart Valve Prosthesis; Heparin; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Topics: Abnormalities, Drug-Induced; Bioprosthesis; Female; Heart Valve Prosthesis; Heparin; Humans; Pregnancy; Pregnancy Complications; Warfarin

Topics: Abnormalities, Drug-Induced; Chondrodysplasia Punctata; Female; Humans; Maxilla; Nasal Bone; Phenotype; Pregnancy; Syndrome; Terminology as Topic; Warfarin

During the past 15 years, we followed 21 patients with prosthetic heart valves who experienced a total of 24 pregnancies at mean age of 31.3 +/- 3.6 years. The course of these patients and their pregnancies were reviewed to evaluate the problems associated with prosthetic heart valves and anticoagulation. Among the 21 patients, the aortic valve (AV) had been replaced in 10 (12 pregnancies), the mitral valve (MV) in nine (10 pregnancies), AV + MV in one (one pregnancy), and the tricuspid valve (TV) in one (one pregnancy). The implanted prosthetic valves were mechanical type in 16 cases (Björk-Shiley 15, Starr-Edwards 1) and bioprosthetic type in six (Hancock 5, Ionescu-Shiley 1). With the exception of one case of intra-uterine fetal death probably related with warfarin therapy, all the patients with bioprosthetic valves underwent successful deliveries. Anticoagulant therapy was employed for 11 pregnancies; warfarin for 10 and subcutaneous heparin for one. No anticoagulant therapy was performed for 13 pregnancies. Ten of the 21 mothers had atrial fibrillation. Eighteen pregnancies (67%) culminated in uneventful deliveries for both mothers and infants. Three mothers (13%) died of thromboembolic complications; two of cerebrovascular accidents and one of acute heart failure caused by thrombus on the replaced valve. All of them had Björk-Shiley valves. Oral warfarin was administered in one of the three, heparin in one and no anticoagulant in the remaining one. Massive maternal bleeding occurred in two cases (8%). There were three cases (12%) of intra-uterine fetal death which were caused by intracranial hemorrhages.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abnormalities, Drug-Induced; Adult; Female; Heart Valve Prosthesis; Hemorrhage; Heparin; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Prognosis; Thromboembolism; Warfarin

Topics: Abnormalities, Drug-Induced; Animals; Cleft Palate; Female; Palate; Pregnancy; Rats; Warfarin

Topics: Abnormalities, Drug-Induced; Female; Heart Valve Prosthesis; Humans; Pregnancy; Warfarin

Topics: Abnormalities, Drug-Induced; Adult; Female; Hernia, Diaphragmatic; Humans; Pregnancy; Thrombophlebitis; Warfarin

Topics: Abnormalities, Drug-Induced; Female; Fetus; Humans; Infant, Newborn; Kidney; Male; Maternal-Fetal Exchange; Pregnancy; Urinary Tract; Warfarin

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Anticoagulants; Bone Diseases; Female; Heart Valve Diseases; Hemorrhage; Heparin; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboembolism; Warfarin

We report a dysmorphic female infant whose mother took warfarin in therapeutic doses during the first 6 weeks of pregnancy. At birth the infant was small for dates and had a triangular facial appearance, micrognathia, microglossia, short fingers and toes, and hypoplastic nails. A skeletal survey revealed hypoplastic distal phalanges in the fingers and toes; there was no epiphyseal stippling. The pattern of malformations present in this infant may either represent the earliest teratogenic effects of warfarin or the fortuitous association of exposure to warfarin and unexplained dysmorphic features.

Topics: Abnormalities, Drug-Induced; Adult; Female; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Trimester, First; Teratogens; Warfarin

We have evaluated a boy who had excessive bleeding and bruising from birth and showed markedly prolonged prothrombin times, partially correctable by oral vitamin K administration. Additional laboratory studies demonstrated decreased activities of plasma factors II, VII, IX, and X; near normal levels of immunologically detected and calcium binding-independent prothrombin; undercarboxylation of prothrombin; excess circulating vitamin K epoxide; decreased excretion of carboxylated glutamic acid residues; and abnormal circulating osteocalcin. These results all are consistent with effects resulting from decreased posttranslational carboxylation secondary to an inborn deficiency of vitamin K epoxide reductase. This individual also had nasal hypoplasia, distal digital hypoplasia, and epiphyseal stippling on infant radiographs, all of which are virtually identical to features seen secondary to first-trimester exposure to coumarin derivatives. Therefore, by inference, the warfarin embryopathy is probably secondary to warfarin's primary pharmacologic effect (interference with vitamin K-dependent posttranslational carboxylation of glutamyl residues of various proteins) and may result from undercarboxylation of osteocalcin or other vitamin K-dependent bone proteins.

Topics: 1-Carboxyglutamic Acid; Abnormalities, Drug-Induced; Calcium-Binding Proteins; Child; Chromatography, High Pressure Liquid; Female; Fetal Diseases; Fingers; Humans; Male; Nose; Osteocalcin; Phenotype; Pregnancy; Prothrombin; Radiography; Vitamin K; Vitamin K 1; Vitamin K Deficiency; Warfarin

Administration of warfarin during pregnancy may cause a rare syndrome characterized by nasal hypoplasia, usually associated with stippled epiphyseal and extraepiphyseal calcifications resembling chondrodysplasia punctata. A case of chondrodysplasia punctata after warfarin with 18 months follow-up is reported.

Topics: Abnormalities, Drug-Induced; Adult; Chondrodysplasia Punctata; Female; Follow-Up Studies; Heart Valve Prosthesis; Humans; Infant, Newborn; Male; Mitral Valve; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Birth defects caused by human teratogens are an important and potentially preventable cause of perinatal morbidity and mortality. Case reports provide an initial suggestion that a specific agent may be a human teratogen and provide the basis for further study. This review discusses the importance of case reports in human teratology and provides guidance in evaluating new case reports.

Topics: Abnormalities, Drug-Induced; Animals; Antiemetics; Dicyclomine; Doxylamine; Drug Combinations; Erythromycin; Female; Humans; Infant, Newborn; Isotretinoin; Medical Records; Pregnancy; Publishing; Pyridoxine; Teratogens; Thalidomide; Tretinoin; Warfarin

A rare congenital nasal deformity due to warfarin embryopathy is reported. The commonest anomalies described in this syndrome are: hypoplasia of the nose, stippling of bone, optic atrophy and mental retardation. The various abnormalities and the mechanism of warfarin teratogenesis are discussed.

Topics: Abnormalities, Drug-Induced; Humans; Infant, Newborn; Male; Nasal Bone; Syndrome; Warfarin

Topics: Abnormalities, Drug-Induced; Anticoagulants; Female; Heparin; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Streptokinase; Warfarin

During the 13 year period 1971 to 1984 there were 38 pregnancies in 21 renal transplant patients at the Johannesburg Hospital. Twenty-two ended with live births and included two sets of twins; there were nine spontaneous abortions, six therapeutic abortions, and one stillbirth. Maternal complications were mild in the majority but five patients suffered deterioration in renal function, two undergoing transplant nephrectomy as a result of this. There were seven neonatal deaths, including both sets of twins; death was due to prematurity in six and congenital malformation (diaphragmatic hernia) in one. A further infant had congenital pyloric stenosis which was corrected surgically. Pregnancies were analysed according to whether or not their outcome was successful. Those with a successful outcome had less exposure to warfarin during pregnancy (p = 0.0025) and showed a tendency towards lower immunosuppressive doses of prednisone and azathioprine although these did not reach significance. Although these results indicate an unhappy prognosis for both the mother and fetus, two redeeming features are to be noted. Pregnancy outcome improved markedly in the latter years, possibly owing to non-exposure to warfarin, less immunosuppression, and improvement in neonatal care, and four of the five mothers who suffered deterioration in renal function were notoriously unco-operative in their medical care. Pregnancy can only be recommended in the transplanted patient who has stable renal function, is compliant in taking of medications, and whose graft is of such age that the immunosuppressive drug dose is minimal. Warfarin should be avoided.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Abortion, Therapeutic; Acute Kidney Injury; Adolescent; Adult; Dose-Response Relationship, Drug; Female; Fetal Death; Humans; Immunosuppressive Agents; Infant, Newborn; Kidney Transplantation; Patient Compliance; Pregnancy; Pregnancy Complications; Warfarin

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Cardiovascular; Rheumatic Heart Disease; Warfarin

This is a case report of an infant born with nasal hypoplasia, stippling of epiphyses, and toe deformities. This embryopathy is due to maternal ingestion of Warfarin during pregnancy. Other defects including ophthalmologic and neurologic abnormalities also occur, but the nasal malformation is the only constant clinical feature.

Topics: Abnormalities, Drug-Induced; Chondrodysplasia Punctata; Female; Humans; Infant, Newborn; Nose; Toes; Warfarin

Topics: Abnormalities, Drug-Induced; Female; Fetal Death; Heart Valve Prosthesis; Heparin; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Hematologic; Thromboembolism; Warfarin

The case of a newborn infant girl with a partial agenesis of the corpus callosum and hypoplasia of the nasal bones is reported. She was the product of a full-term pregnancy of a woman who had previously undergone mitral valve replacement with a Björk-Shiley prosthesis and had been maintained on oral anticoagulants (sodium warfarin) until the 38th week of gestation. This case underlines: 1) The need for maintaining an adequate anticoagulation in pregnant women with a mechanical prosthesis. 2) The potential risks of fetal malformations when the oral anticoagulants are given during the first trimester of pregnancy and of fetal hemorrhagic complications when these drugs are administered during the last two trimesters of gestation. 3) The lack of effective pharmacological alternatives to coumarin drugs, which can allow an adequate anticoagulation in the mother with minimal hazards for the fetus.

Topics: Abnormalities, Drug-Induced; Adult; Agenesis of Corpus Callosum; Female; Heart Valve Prosthesis; Humans; Infant, Newborn; Nasal Bone; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

The Obstetric Drug Information Service at the Queen Victoria Medical Center in Melbourne, Australia aims to provide relevant information relating to drug use in pregnancy. A preliminary study conducted by the Center revealed that 62.5% of pregnant women consumed drugs during their pregnancies (excluding iron and vitamins), with an average of 3 drugs per woman. Certain drugs are relatively safer than others, and the selection of the appropriate drug for a pregnant patient is very important to the future health and well-being of the child. At least 5% of all birth defects are drug induced. The drugs that produce fetal abnormalities are called "dysmorphogens" or "teratogens". General principles of drug use in pregnancy are outlined. These include the following: 1) no drug should be considered 100% safe to the developing fetus, including topical preparations; 2) a true indication must be present for the administration of any drug; 3) the potential benefits should always be weighed against the possible hazards of that drug to the mother and the fetus; and 4) the effect of a drug on the fetus may not necessarily be the same as the intended pharmacological effect on the mother. The following specific drug induced embryopathies are reviewed: fetal alcohol syndrome; Warfarin syndrome; fetal hydantoin syndrome; stilbestrol (diethylstilbestrol, DES) syndrome, VACTERL syndrome, and thalidomide embryopathy. Drugs which are safe for use in pregnancy are analgesics, hypnosedatives, antibiotics, antiemetics and antihistamines, psychotherapeutic drugs, antihypertensive drugs, antituberculous drugs, antimalarial drugs, antithyroid drugs, and antidiabetic drugs.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Analgesics; Anti-Bacterial Agents; Antiemetics; Antihypertensive Agents; Antimalarials; Antitubercular Agents; Diethylstilbestrol; Drug-Related Side Effects and Adverse Reactions; Female; Fetal Alcohol Spectrum Disorders; Fetus; Histamine H1 Antagonists; Humans; Hydantoins; Hypnotics and Sedatives; Hypoglycemic Agents; Infant, Newborn; Pregnancy; Pregnancy Complications; Psychotropic Drugs; Warfarin

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adult; Female; Heart Valve Prosthesis; Heparin; Humans; Mitral Valve; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Topics: Abnormalities, Drug-Induced; Abortion, Therapeutic; Endocarditis, Bacterial; Female; Heart Diseases; Heart Failure; Heart Valve Prosthesis; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Two siblings were noted to have the physical stigmata of the fetal warfarin syndrome. Their mother had received warfarin sodium for thrombophlebitis during both pregnancies but not during that of an unaffected sibling. Teratogens may produce syndromes that mimic genetic disease in both phenotype and familial aggregation.

Topics: Abnormalities, Drug-Induced; Adult; Cataract; Child, Preschool; Chondrodysplasia Punctata; Female; Humans; Infant; Infant, Newborn; Male; Maternal-Fetal Exchange; Nose; Pregnancy; Pregnancy Complications, Cardiovascular; Teratogens; Thrombophlebitis; Warfarin

Topics: Abnormalities, Drug-Induced; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Warfarin

A retrospective analysis of 40 patients with cardiac disease who received sodium warfarin (Coumadin) therapy during pregnancy has been performed. The fetal mortality was 12,5%, but no case of congenital epiphyseal stippling was detected. The incidence of maternal postpartum haemorrhage was high. Warfarin should whenever possible be withheld during the 1st trimester of pregnancy and replaced by heparin.

Topics: Abnormalities, Drug-Induced; Adult; Female; Fetal Death; Fetus; Heart Valve Diseases; Humans; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Retrospective Studies; Rheumatic Heart Disease; Warfarin

Prenatal exposure to oral anticoagulants during pregnancy may result in defective fetal development or life-threatening hemorrhage. Fetal exposure during the first eight weeks of pregnancy may cause abnormal development of the facial structures, hypoplastic digits, strippled epiphyses, and mental retardation. Midtrimester exposure may result in optic atrophy, faulty brain growth, and developmental retardation. Third-trimester exposure may produce fetal anticoagulation, predisposing the infant to life-threatening hemorrhage in the perinatal period. Anticoagulation with heparin sodium does not provide a clearly safe alternative, since this therapy has been associated with excessive fetal loss.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Administration, Oral; Adult; Anticoagulants; Body Weight; Chondrodysplasia Punctata; Female; Fetus; Gestational Age; Humans; Infant, Newborn; Maternal-Fetal Exchange; Optic Atrophy; Pregnancy; Pregnancy Complications, Cardiovascular; Rheumatic Heart Disease; Vitamin K; Warfarin

A case is reported of a baby born with congenital abnormalities due to maternal ingestion of warfarin during pregnancy. Warfarin is known to be teratogenic, producing characteristic abnormalities, namely a hypoplastic nose, stippled epiphyses, and skeletal abnormalities. A variety of ocular abnormalities have been reported. Ophthalmologists should seek a history of maternal warfarin ingestion when seeing a baby with congenital ocular abnormalities. They should also be aware of the possible teratogenic effects when considering warfarin therapy for a woman of childbearing age.

Topics: Abnormalities, Drug-Induced; Female; Humans; Infant, Newborn; Male; Nose; Pregnancy; Syndrome; Warfarin

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Embryo, Mammalian; Female; Fetal Death; Humans; Infant, Newborn; Pregnancy; Warfarin

The vitamin K-dependent hemostatic factors are present in reduced quantities at birth and may decrease further in the first few days of life. Administration of vitamin K1 on day 1 prevents hemorrhagic disease of the newborn. Maternal ingestion of anticonvulsants puts the newborn at greater risk from hemorrhage, possibly as a result of induction of fetal microsomal enzymes with a resultant increased oxidative degradation of vitamin K which gives rise to a vitamin K deficiency and other concomitant clinical results, for example skeletal defects. Evidence for this sequence of events is presented and the widespread effect of vitamin K deficiency on the fetus is discussed.

Topics: Abnormalities, Drug-Induced; Animals; Blood Coagulation Factors; Bone and Bones; Chick Embryo; Female; Hemostasis; Humans; Maternal-Fetal Exchange; Microsomes, Liver; Oxidation-Reduction; Phenytoin; Pregnancy; Vitamin K 1; Vitamin K Deficiency; Vitamin K Deficiency Bleeding; Warfarin

Topics: Abnormalities, Drug-Induced; Humans; Infant, Newborn; Male; Nose; Syndrome; Warfarin

Topics: Abnormalities, Drug-Induced; Adult; Female; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, First; Spleen; Teratogens; Thrombophlebitis; Warfarin

Topics: Abnormalities, Drug-Induced; Adult; Female; Humans; Infant, Newborn; Male; Phenindione; Pregnancy; Warfarin

Topics: Abnormalities, Drug-Induced; Chondrodysplasia Punctata; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Warfarin

Topics: Abnormalities, Drug-Induced; Adult; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Maternal-Fetal Exchange; Osteochondrodysplasias; Pregnancy; Radiography; Warfarin

Two mothers with heart valve prosthesis were treated with warfarin during pregnancy. In the first case a caesarean section was done one week after replacement of warfarin with heparin. The baby died of cerebral and pulmonary hemorrhage. The second mother had a male infant by caesarean section. The baby showed warfarin-induced embryopathy with nasal hypoplasia and stippled epiphyses (chondrodysplasia punctata). Nasal hypoplasia with or without stippled epiphyses has now been reported in 11 infants born to mothers treated with warfarin during the first trimester, and a causal association is probable. In view of the risks to both mother and fetus in women with prosthetic cardiac valves it is recommended that therapeutic abortion be advised as the first alternative.

Topics: Abnormalities, Drug-Induced; Adult; Cerebral Hemorrhage; Cesarean Section; Chondrodysplasia Punctata; Female; Fetus; Heart Valve Prosthesis; Hemorrhage; Heparin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lung Diseases; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Topics: Abnormalities, Drug-Induced; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Microcephaly; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombophlebitis; Warfarin

Topics: Abnormalities, Drug-Induced; Female; Gestational Age; Humans; Maternal-Fetal Exchange; Pregnancy; Time Factors; Warfarin

Topics: Abnormalities, Drug-Induced; Adult; Female; Humans; Infant, Newborn; Microcephaly; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombophlebitis; Warfarin

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Humans; Infant; Male; Time Factors; Warfarin

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Female; Humans; Infant, Newborn; Pregnancy; Warfarin

Topics: Abnormalities, Drug-Induced; Bone and Bones; Eye Abnormalities; Female; Growth; History of Medicine; Humans; Infant, Newborn; Nose Deformities, Acquired; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Warfarin

Histological and anthropometric studies were made of the hands and face of a 17-week-old (postmenstrual) human fetus that was exposed to warfarin throughout gestation. The fetus had marked nasal hypoplasia and the facial cartilages contained discrete foci of abnormal cartilage. When compared with age-matched control fetuses hand pattern profile analysis showed that the brachydactyly was due to shortening of the terminal phalanges. Histologically chondrogenesis was disordered in the carpals and phalanges, with the most deviant development occurring at the distal ends of the terminal phalanges. In none of the areas of abnormal cartilage was there evidence of hemorrhage or hemosiderin deposition. It is our contention that warfarin is teratogenic in human beings and that its teratogenicity is not due to focal hemorrhage.

Topics: Abnormalities, Drug-Induced; Abortion, Induced; Anthropometry; Cardiomyopathy, Hypertrophic; Cartilage; Face; Female; Fingers; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

This report is based on information obtained from a questionnaire sent to major cardiac centres in the United Kingdom. This produced details of 39 pregnancies in 34 patients after valve replacement. The 39 pregnancies gave rise to 30 healthy babies. The small size of the series probably reflects both the increasing rarity of young women with rheumatic heart disease in this country and the cautious attitude of their cardiologists. This makes it likely that these women represented the best end of the spectrum of cardiac function after valve replacement. Twenty-four pregnancies in 20 women who were not given anticoagulants producted 23 healthy babies and 1 spontaneous abortion. This group comprised 6 patients with free aortic homografts, 1 patient with a fascia lata mitral valve, 1 with a Beall tricuspid prosthesis, 1 with a combined mitral homograft and Starr Edwards aortic prosthesis, and 1 with mitral and aortic frame-mounted fascia lata valves. There were no maternal deaths or thromboembolic complications in this group which included 5 patients who were in atrial fibrillation. Fifteen pregnancies in 14 women who received anticoagulants gave rise to 7 healthy babies. The fetal losses were one stillbirth, one intrauterine death at 34 weeks, and 3 spontaneous abortions; one surviving child has hydrocephalus as a result of blood clot and there were 2 maternal deaths. This group included 13 patients with Starr Edwards valves, 11 mitral and 2 aortic. A patient with a Hammersmith mitral valve was the only one to have been treated with heparin and her valve thrombosed. One patient with a mounted mitral homograft had a cerebral embolus. Nine of these patients were in atrial fibrillation. In 3 additional patients the valve replacement was carried out during pregnancy. Two of the patients survived operation. In one of these who was treated with warfarin the pregnancy well, but there is an increased fetal wastage in patients pregnancy gave rise to a congenitally malformed baby who died in the neonatal period. The baby born to the mother who did not receive anticoagulants has a hare-lip and talipes. Women with artificial valves can tolerate the haemodynamic load of pregnancy well, but there is an increased fetal wastage in patients taking oral anticoagulants. This is probably largely attributable to fetal haemorrhage but there is also a risk of malformation caused by a teratogenic effect of warfarin. Experience gained in non-pregnant patients suggests that withholdin

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adolescent; Adult; Anticoagulants; Female; Fetal Death; Heart Valve Prosthesis; Heparin; Humans; Intracranial Embolism and Thrombosis; Postoperative Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Topics: Abnormalities, Drug-Induced; Adult; Female; Fetus; Humans; Infant, Newborn; Pregnancy; Thrombophlebitis; Time Factors; Warfarin

Topics: Abnormalities, Drug-Induced; Alcoholism; Chondrodysplasia Punctata; Diazepam; Digitalis Glycosides; Erythromycin; Female; Fetus; Heart Valve Prosthesis; Heparin; Humans; Infant, Newborn; Penicillin G Benzathine; Pregnancy; Pregnancy Complications; Sulfisoxazole; Syphilis; Thrombosis; Warfarin

Topics: Abnormalities, Drug-Induced; Adult; Chondrodysplasia Punctata; Digitoxin; Digoxin; Female; Fetus; Heart Valve Prosthesis; Heparin; Humans; Infant, Newborn; Male; Placenta Diseases; Pregnancy; Pregnancy Complications; Radiography; Sulfisoxazole; Thrombosis; Warfarin

Topics: Abnormalities, Drug-Induced; Alcoholism; Cerebrovascular Disorders; Chondrodysplasia Punctata; Contraceptives, Oral; Diazepam; Female; Fetus; Furosemide; Humans; Hypertension; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; Radiography; Rheumatic Heart Disease; Stress, Psychological; Warfarin

A case of congenital stippled epiphyses is presented, and attention is drawn to the possibility that this condition was caused by maternal ingestion of warfarin during early pregnancy.

Topics: Abnormalities, Drug-Induced; Adult; Chondrodysplasia Punctata; Female; Humans; Infant, Newborn; Pregnancy; Warfarin

Topics: Abnormalities, Drug-Induced; Alkylating Agents; Amphetamine; Androgens; Anticonvulsants; Antithyroid Agents; Carcinogens; Cerebral Palsy; Diethylstilbestrol; Estrogens; Female; Fetus; Folic Acid Antagonists; Gestational Age; Humans; Lead; Maternal-Fetal Exchange; Methylmercury Compounds; Neoplasms; Polychlorinated Biphenyls; Pregnancy; Progesterone; Streptomycin; Tetracycline; Thalidomide; Tooth; Transposition of Great Vessels; Warfarin

Topics: Abnormalities, Drug-Induced; Animals; Bone and Bones; Cleft Lip; Cleft Palate; Dose-Response Relationship, Drug; Embryo Implantation; Embryo, Mammalian; Female; Fetal Death; Hemorrhage; Mice; Mice, Inbred Strains; Placenta Diseases; Pregnancy; Prothrombin Time; Sodium Chloride; Time Factors; Vitamin K; Vitamin K 1; Warfarin

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Aortic Valve; Aortic Valve Insufficiency; Female; Fetal Death; Heart Valve Prosthesis; Heparin; Humans; Labor, Obstetric; Mitral Valve; Mitral Valve Insufficiency; Phenindione; Postoperative Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboembolism; Warfarin

Topics: Abnormalities, Drug-Induced; Adult; Female; Heart Valve Prosthesis; Humans; Infant, Newborn; Nose Deformities, Acquired; Pregnancy; Warfarin