vitamin-k-semiquinone-radical and Abnormalities--Drug-Induced

Managing anticoagulation in pregnant women with mechanical heart valves remains challenging. Our aim was to evaluate the effectiveness and safety of 4 regimens in these women.. Relevant studies published before June 2015 were collected in several databases and analyzed with RevMan version 5.3 and SPSS version 19.0. Four regimens were defined as follows: a regimen of a vitamin K antagonist (VKA) throughout pregnancy; a heparin (H)/VKA regimen using VKAs except for unfractionated heparin (UFH) or low molecular weight heparin (LMWH) during 6-12 weeks of pregnancy; a LMWH regimen of adjusted LMWH doses throughout pregnancy; and a UFH regimen of adjusted UFH doses throughout pregnancy. The low warfarin dose in the VKA regimen was defined as 5 mg/d or less.. Fifty-one studies comprising 2113 pregnancies in 1538 women were included. The rate of fetal wastage was significantly higher in the high warfarin dose subgroup than in the low dose one. Compared with the H/VKA regimen, the rate of maternal major thromboembolic event in the low-dose VKA regimen group was significantly lower, although the fetal outcomes were similar. Compared with the H/VKA regimen, the rate of fetal wastage in the LMWH regimen group was significantly lower, and the maternal outcomes were similar. The UFH regimen presented the worst maternal and fetal outcomes.. In the absence of large prospective trials, this meta-analysis showed that the VKA regimen should be best for pregnant women with a low warfarin dose, and the H/VKA regimen might be reasonable for those with a high warfarin dose. The LMWH regimen could be used for those who refuse VKA.

Topics: Abnormalities, Drug-Induced; Abortion, Induced; Abortion, Spontaneous; Anticoagulants; Dose-Response Relationship, Drug; Female; Heart Valve Prosthesis; Heparin; Humans; Maternal Mortality; Pregnancy; Pregnancy Complications, Cardiovascular; Stillbirth; Thromboembolism; Vitamin K

Even though from preclinical testing to drug risk labeling, the situation with drugs in pregnancy has improved substantially since the thalidomide scandal, there is still an increasing need to provide healthcare professionals and patients with updated individualized risk information for clinical decision making. For the majority of drugs, clinical experience is still insufficient with respect to their safety in pregnancy. There is often uncertainty in how to interpret the available scientific data. Based on 20 years of experience with Teratology Information Services (TIS) cooperating in the European Network of Teratology Information Services (ENTIS) methods of risk interpretation, follow-up of exposed pregnancies through the consultation process and their evaluation is discussed. Vitamin K antagonists, isotretinoin and angiotensin (AT) II-receptor-antagonists are presented as examples of misinterpretation of drug risks and subjects of research based on observational clinical data recorded in TIS. As many TIS are poorly funded, advocacy is necessary by establishing contacts with decision makers in health politics and administration, informing them of the high return in terms of health outcomes and cost savings provided by TIS as reference institutions in clinical teratology.

Topics: 4-Hydroxycoumarins; Abnormalities, Drug-Induced; Angiotensin Receptor Antagonists; Anticoagulants; Drug Information Services; Female; Humans; Pregnancy; Pregnancy Complications; Retinoids; Risk Assessment; Teratology; Vitamin K

In todays medicine, anticoagulant drugs like heparin and coumadin derivatives have become indispensable for the treatment of thrombo-embolic diseases. Heparin, consisting of long poly-sulfated polysaccharide chains of variable length and sequences is mostly derived from porcine mucosa. Its bioavailability by other than the parenteral way of administration is almost negligible. Therefore, with only few exceptions, it is almost exclusively applied in hospitalized patients (short-term therapy) or to bridge 2 phases of treatment with oral anticoagulant drugs. Today, besides the conventional high-molecular weight heparins, new fractionated heparins are gaining more and more attention. They offer the advantage of a more reliable resorption from the subcutaneous tissue and thus warrant reliable plasma levels. In many recent randomized trials of deep vein thrombosis and pulmonary embolism, those fractionated heparins have proven to successfully substitute for intravenously applied, aPTT-controlled unfractionated heparin. It remains however open, whether this also translates into the prevention of arterial thrombo-embolic diseases. Heparin may not pass through the placental barrier nor into the milk and is regarded non-teratogenic. Therefore, it may be regarded the ideal anticoagulant for pregnant women and lactating mothers. Those women, however, still carry the heparin-associated risk of bleeding and osteoporosis. In comparison: Coumadin derivatives interfere with the carboxylation of the clotting factors II, VII, IX, and X as well as proteins C and S. By inhibiting the synthesis of these proteins they shift the haemostatic balance to a lower level. In addition, they are almost completely bioavailable by the enteral pathway. They are, therefore, regarded the drugs of choice for long-term anticoagulant therapy in patients at particular thromboembolic risk. For their therapeutic range, being extremely narrow, meticulous drug monitoring by repeated INR-measurements as well as a reliable compliance of the patient to drug intake and dietary restrictions are mandatory to exclude phases with over- or under-anticoagulation. Above all, coumadin therapy is characterized by numerous drug interactions. Thus, whenever the basal medication is changed, for whatever reason, more intense care must be laid to drug monitoring, and the intervals for INR determinations must transiently be shortened. Coumadin derivatives do pass through the placental barrier and in minor amounts also

Topics: Abnormalities, Drug-Induced; Anticoagulants; Cardiovascular Diseases; Coumarins; Drug Interactions; Female; Heparin; Heparinoids; Humans; Infant, Newborn; Partial Thromboplastin Time; Pregnancy; Randomized Controlled Trials as Topic; Risk Factors; Thromboembolism; Vitamin K

Ten patients with maxillonasal hypoplasia (Binder "syndrome"), who were prenatally exposed to phenytoin (usually in combination with other anticonvulsants), were identified retrospectively. In addition to their facial anomalies, 6 of the patients were radiographed neonatally and showed punctate calcification, characteristic of chondrodysplasia punctata. Evidence is presented that the facial abnormalities seen in these children are due to anticonvulsant-induced vitamin K deficiency, causing abnormal development of the cartilaginous nasal septum. We propose that early vitamin K supplementation of at-risk pregnancies may prevent the development of maxillonasal hypoplasia, which in some patients is severely disfiguring and causes great emotional distress. Correction of this facial defect requires surgical and dental treatment over a long period of time.

Topics: Abnormalities, Drug-Induced; Adult; Anticonvulsants; Child; Chondrodysplasia Punctata; Face; Female; Humans; Infant; Infant, Newborn; Male; Phenytoin; Pregnancy; Prenatal Exposure Delayed Effects; Vitamin K; Vitamin K Deficiency

Coumarin derivatives and anticonvulsants administered during pregnancy enter the fetal circulation, interfering with the action of vitamin K. Vitamin K plays a crucial part in the gamma-carboxylation of glutamic acid residues of the vitamin K-dependent coagulation factors prothrombin, FVII, FIX, and FX. Other vitamin K-dependent proteins in the coagulation cascade are protein C and protein S. Vitamin K-dependent bone proteins are osteocalcin and gamma-carboxyglutamate matrix protein. Administration of coumarol derivatives results in under carboxylation of the vitamin K-dependent proteins. Anticoagulation therapy with warfarin is followed by an increased risk of embryopathy, which has been shown to be greatest between gestational weeks 6 and 12. Administration of warfarin is also followed by an increased risk both of fetal intraventricular hemorrhage, and of cerebral microbleedings, which may result in microencephaly and mental retardation. Treatment with coumarol derivatives should therefore be avoided during pregnancy, even in pregnant women with artificial heart valves, and replaced by heparin. Hemorrhage in the newborn related to the use of anticonvulsant drugs during pregnancy occurs very early within the first 24 hours, probably due to increased degradation of vitamin K. Transplacental administration of vitamin K has been shown to prevent neonatal hemorrhage induced by maternal anticonvulsant therapy. Prophylactic administration of vitamin K, especially by intramuscular injection, has been reported to be associated with an increased risk of childhood cancer. However, subsequent extensive studies have yielded no evidence of any relationship between prophylactic vitamin K administration and the occurrence of childhood cancer.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Anticonvulsants; Blood Coagulation Factors; Child; Cohort Studies; Coumarins; Epilepsy; Female; Fetal Diseases; Hemorrhage; Humans; Infant, Newborn; Maternal-Fetal Exchange; Neoplasms; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Protein Processing, Post-Translational; Sweden; Thrombosis; United Kingdom; Vitamin K; Vitamin K Deficiency

Epilepsy is the most common neurological disease of females in reproductive age. Problems concerning contraception, reproduction, teratogenicity and antiepileptic therapy preceding and during pregnancy are discussed and recommendations made. We underline the advantages of a planned pregnancy with optimal adjustment of antiepileptic drug therapy and recommend prophylactic treatment with folic acid before and during, and with vitamin K towards the end of pregnancy.. Epilepsy is the most common neurological disease of women of reproductive age. Until the mid 20-th century, its diagnosis meant no possibility of marriage and children. The advances of therapy, however, have assured that most patients can live a normal life. The major points are underscored including the interaction between epilepsy and pregnancy involving the mechanisms of congenital anomalies. The frequency of attacks during pregnancy. Pregnancy complications under epilepsy. Epilepsy and fetal malformations. Pharmacological mechanisms of teratogenicity: epoxides, free radicals, folic acid deficiency, teratogenicity of new antiepileptics and preparation with indications. Pharmacotherapy before and during pregnancy, including contraception in attack-prone patients: oral contraceptives and hormonal abortion (RU-486). Special pharmacokinetics of antiepileptics during pregnancy; dose selection and adjustment, bleeding risk and vitamin K substitution. The planning of pregnancy in epilepsy and prenatal diagnosis. Regarding indications based on existing data, it can be stated that there is a genetically higher risk of congenital malformations with primary epilepsy of parents. The risk of defect depends on the dose and quantity of medications given irrespective of the type of antiepileptics. In stabilized epilepsy, the probability of giving birth to a normal child is over 90%. The risk of congenital defects in the offspring of seizure-prone parents on genetic, and, in the case of antiepileptic therapy on medicament-toxicological grounds, is on the average 2-3 times higher. There is an elevated danger posed for the fetus by the tonic-clonic seizures of the mother through asphyxia and direct injuries by falling. The risk from an uncontrolled epilepsy is higher than the risk of malformation through antiepileptics. It is possible but statistically not proven that valproate results in an increased rate of spina bifida (1% selective risk). Prenatal diagnosis allows detection of early defects to decide on abortion or preterm birth to reduce the neurological deficit.

Topics: Abnormalities, Drug-Induced; Animals; Anticonvulsants; Contraception; Epilepsy; Female; Folic Acid; Free Radicals; Humans; Inactivation, Metabolic; Infant, Newborn; Pregnancy; Pregnancy Complications; Risk Factors; Vitamin K

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Breast Feeding; Clinical Protocols; Epilepsy; Female; Humans; Pregnancy; Pregnancy Complications; Teratogens; Vitamin K

Pregnant women with epilepsy are at increased risk of seizures and complications. An increase in seizure frequency is seen in 25-30% of pregnant women with epilepsy; the offspring of mothers who experienced seizures during pregnancy are at a 2.5 times higher risk for seizures later in life. One of the main reasons for the increase in seizures during pregnancy is a decline in plasma concentrations of antiepileptic drug (AED) that occurs as pregnancy progresses, largely as a result of marked alterations in plasma protein binding. It is well known that epilepsy represents a risk for a variety of adverse pregnancy outcomes or malformations, especially in polytherapy. The adverse outcomes range from dysmorphic features to hemorrhagic disorders resulting from a deficiency of vitamin K-dependent clotting factors or to spina bifida. Folic acid supplements appear to reduce the risk of spina bifida. A strong genetic link seems to exist for many of the malformations that occur, and more research is required in this field. In the meantime, there are interventions that clinicians can already make to reduce the risk of adverse outcomes, such as seizure control without toxicity, monotherapy, and preconceptual use of vitamins with folate.

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Epilepsy; Female; Fertility; Fetal Diseases; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Risk Factors; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Barbiturates; Blood Coagulation Disorders; Chromosome Aberrations; Chromosome Disorders; Female; Fetus; Folic Acid; Humans; Infant, Newborn; Phenytoin; Pregnancy; Pregnancy Complications; Primidone; Succinimides; Trimethadione; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Blood Coagulation; Epilepsy; Female; Fetal Death; Fetus; Folic Acid Deficiency; Humans; Infant, Newborn; Maternal-Fetal Exchange; Obstetric Labor Complications; Pregnancy; Pregnancy Complications; Vitamin B 12; Vitamin D; Vitamin D Deficiency; Vitamin K

Topics: Abnormalities, Drug-Induced; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Coumarins; Embolism; Female; Fetus; Heart Valve Prosthesis; Hemorrhage; Heparin; Humans; Infant, Newborn; Maternal-Fetal Exchange; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombophlebitis; Uterus; Vitamin K

Topics: Abnormalities, Drug-Induced; Anti-Bacterial Agents; Anticoagulants; Antimetabolites; Antineoplastic Agents; Antithyroid Agents; Female; Fetal Diseases; Fetus; Hemolysis; Hormones; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Pregnancy; Reserpine; Salicylates; Thalidomide; Tolbutamide; Vitamin K

Topics: Abnormalities, Drug-Induced; Adrenal Cortex Hormones; Anti-Bacterial Agents; Antineoplastic Agents; Appetite Depressants; Female; Hormones; Humans; Hypoglycemic Agents; Iodides; Iodine; Maternal-Fetal Exchange; Metronidazole; Narcotic Antagonists; Nitrofurantoin; Podophyllin; Pregnancy; Sulfonamides; Toxicology; Vaccines; Vitamin K; Vitamins

Topics: Abnormalities, Drug-Induced; Adrenal Cortex Hormones; Analgesics; Analgesics, Non-Narcotic; Anesthetics; Anti-Bacterial Agents; Antipyretics; Central Nervous System Stimulants; Drug Therapy; Female; Fetus; Gonadal Steroid Hormones; Histamine H1 Antagonists; Humans; Hypnotics and Sedatives; Infant; Infant, Newborn; Maternal-Fetal Exchange; Otolaryngology; Pharmacology; Pregnancy; Pregnancy Complications; Sulfonamides; Toxicology; Tranquilizing Agents; Vasodilator Agents; Vitamin K

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

The aim of this observational cohort study was to specify the risk of the vitamin K antagonist (VKA) phenprocoumon during first trimester of pregnancy, in particular to estimate the risk of birth defects and spontaneous fetal loss. Four hundred eight pregnancies with phenprocoumon exposure were compared to 1,642 pregnancies neither exposed to VKA nor to other major teratogens or fetotoxicants. There was no typical warfarin embryopathy in our exposed cohort. However, the overall rate of major birth defects was significantly increased (7.4 % vs 2.3 %; adjusted odds ratio [OR

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Abortion, Therapeutic; Adult; Anticoagulants; Birth Weight; Blood Coagulation; Drug Administration Schedule; Drug Substitution; Female; Humans; Infant, Newborn; Logistic Models; Odds Ratio; Phenprocoumon; Pregnancy; Pregnancy Trimester, First; Premature Birth; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vitamin K; Young Adult

Epilepsy is the most commonly encountered serious neurological problem in obstetrical practice. The disease and treating medications may have significant impact on contraceptive choice, efficacy and reproduction.. This article seeks to inform general practitioners (GPs) about current developments in the field of pregnancy care for women with epilepsy and to foster a collaborative approach in their management.. The care of a pregnant woman with epilepsy needs to start well before pregnancy occurs, while she is still under the care of a GP, especially if she is on antiepileptic medication. GPs are familiar with the concept of GP management plans and team care arrangements for chronic diseases. This model of team care should be extended to the management of women with epilepsy with regards to reproduction. It is hoped this will enhance perinatal outcomes for women and their infants by encouraging shared communication between the obstetrician, neurologist and GP.

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Contraceptive Agents; Dietary Supplements; Epilepsy; Female; Fertility; Folic Acid; General Practice; Humans; Interdisciplinary Communication; Neurology; Obstetrics; Patient Care Team; Postnatal Care; Preconception Care; Pregnancy; Pregnancy Complications; Prenatal Care; Vitamin K

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; Antiphospholipid Syndrome; Female; Heparin, Low-Molecular-Weight; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Infant, Newborn; Infant, Premature, Diseases; Maxillofacial Abnormalities; Phenprocoumon; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Ultrasonography, Prenatal; Vitamin K

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adverse Drug Reaction Reporting Systems; Anticoagulants; Coumarins; Female; Humans; Pregnancy; Pregnancy Trimester, First; Proportional Hazards Models; Vitamin K

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

LMWHs are the major anticoagulant/antithrombotic treatment given to pregnant women to prevent and treat venous thromboembolism despite the absence of specific clinical trials. An emerging indication, the prevention of adverse pregnancy outcomes, is under investigation. During pregnancy, LMWHs seem to be safe and efficient. Some uncertainties remain about the management of rare potential side effects, particularly in the event of heparin intolerance and with cross-reactivity to danaparoid sodium.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Contraindications; Dermatitis, Allergic Contact; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Pregnancy; Pregnancy Complications, Hematologic; Thrombocytopenia; Thrombophilia; Venous Thrombosis; Vitamin K

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

There is concern regarding the teratogenic risks of antiepileptic drugs (AEDs) and the effect of seizures during pregnancy. Pre-pregnancy assessment and collaboration with the patient's neurologist may improve outcome. This study examined by postal questionnaire how senior obstetricians in Scotland cared for their patients with epilepsy in March 1994. One hundred and nine of 127 (86%) practising obstetricians representative of those working in both teaching and district general hospitals in Scotland responded. Only 16% of district general hospital obstetricians had an accessible epilepsy clinic/service and 19% a neurologist. Only 21% of all respondents considered that pregnancy counselling was being provided by a neurologist/epilepsy specialist, and only 43% were usually able to organize combined specialist care with an interested physician/neurologist. Most (79%) were happy with the concept of collaborative care. Many were uncertain as to the importance of recording epilepsy severity, genetic aspects, making changes to AEDs, monitoring drug levels, the use of vitamin K and breast feeding. Sixty-four per cent did not change their management of labour. Twenty per cent were dissatisfied with the present care of their patients with epilepsy. Over 90% considered guidelines to be important. This survey demonstrates the need for existing epilepsy services to be more accessible to all obstetricians in Scotland, particularly for those working in district general hospitals.

Topics: Abnormalities, Drug-Induced; Adult; Anticonvulsants; Attitude of Health Personnel; Drug Monitoring; Epilepsy; Female; Humans; Infant, Newborn; Male; Middle Aged; Neurologic Examination; Patient Care Team; Pregnancy; Pregnancy Complications; Ultrasonography, Prenatal; Vitamin K

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

Special aspects of antiepileptic therapy during pregnancy in epileptic women are described. A monotherapy should be preferred. Due to changes in the pharmacokinetics of antiepileptic drugs, plasma level checks must be performed every four weeks during early pregnancy. The possible teratogenetic effects of anticonvulsants and other factors tending to increase of malformation rate are discussed. An explanation is given for the use of prophylactic folic acid and Vitamin K treatment in connection with antiepileptic therapy. The benefits of counselling prior to pregnancy are discussed.

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Breast Feeding; Epilepsy; Female; Folic Acid; Humans; Infant, Newborn; Kinetics; Long-Term Care; Pregnancy; Pregnancy Complications; Vitamin K

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

Sixteen pregnancies were followed up in 13 patients with prosthetic heart valves: 8 pregnancies went to term under oral anticoagulation, 4 under heparin and 4 without anticoagulation. 9 healthy normal children were delivered; there were 2 still births and 5 abortions. On the maternal side 3 haemorrhages and thromboembolic episodes which involved 2 patients on heparin, one of whom died, were observed. The following points are apparent from our observations and a review of the existing medical literature: --the risk of thromboembolism is not increased. The marked clotting tendency of maternal blood post-partum contraindicates the withdrawal of anticoagulants during this critical period; --haemorrhagic complications are common with anticoagulants; --foetal loss is greatly increased; --the teratogenecity of vitamin-K antagonists is certain, but the risk is small. The problems of anticoagulation are discussed; theoretically heparin should be given during the 1st trimestre and from the 38th week to the second post-partum week. The patients should be closely supervised by both obstetrician and cardiologist and hospitalisation is advised for the last month of pregnancy. Normal vaginal delivery is usually possible.

Topics: Abnormalities, Drug-Induced; Abortion, Induced; Adult; Anticoagulants; Female; Fetal Death; Heart Valve Prosthesis; Hemorrhage; Heparin; Humans; Labor, Obstetric; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboembolism; Vitamin K

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Epilepsy; Family Planning Services; Female; Humans; Infant, Newborn; Lactation; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Vitamin D; Vitamin K

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; Aminopterin; Anti-Bacterial Agents; Antimetabolites; Chloramphenicol; Cortisone; Female; Fetal Diseases; Fetus; Humans; Infant, Newborn; Infant, Newborn, Diseases; Iodides; Iodine Isotopes; North Carolina; Opium; Oxygen; Poison Control Centers; Pregnancy; Pregnancy Complications; Progestins; Quinine; Reserpine; Sulfonamides; Testosterone; Thalidomide; Thiouracil; Toxicology; Universities; Vitamin K

Topics: Abnormalities, Drug-Induced; Adrenal Cortex Hormones; Anti-Bacterial Agents; Barbiturates; Chloramphenicol; Demeclocycline; Female; Fetal Diseases; Humans; Infant, Newborn; Maternal-Fetal Exchange; Meperidine; Oxytetracycline; Pregnancy; Progesterone; Reserpine; Streptomycin; Sulfisoxazole; Tetracycline; Thiouracil; Thyroxine; Toxicology; Vitamin K

Topics: Abnormalities, Drug-Induced; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anti-Bacterial Agents; Anticoagulants; Antihypertensive Agents; Antineoplastic Agents; Barbiturates; Chlorpromazine; Gonadal Steroid Hormones; Hypoglycemic Agents; Pregnancy; Progestins; Streptomycin; Sulfonamides; Tetracycline; Thyroid Hormones; Toxicology; Vitamin K; Vitamins