phenylephrine-hydrochloride and Abnormalities--Drug-Induced

Concerns about the safety of carbimazole in pregnancy were raised in 1985. Since this time many reports of children believed to have been affected by carbimazole in utero have appeared in the medical literature. Initial reports were of an increased incidence of scalp defects in the infants of treated mothers, but many other anomalies have now been described. Choanal atresia, gastrointestinal anomalies-particularly esophageal atresia, athelia/hypothelia, developmental delay, hearing loss, and dysmorphic facial features have all been reported. The phenotype associated with exposure to carbimazole appears to be rare but specific with distinctive facial features. We report on two new cases of carbimazole embryopathy with strikingly similar facial features.

Topics: Abnormalities, Drug-Induced; Adolescent; Antithyroid Agents; Carbimazole; Child; Ear; Eyebrows; Female; Humans; Hyperthyroidism; Nose; Pregnancy; Pregnancy Complications; Thyrotoxicosis

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

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

Review of published cases of pregnancies in which coumarin derivatives or heparin were administered demonstrates that use of either class of anticoagulant carries substantial risks. Of 418 reported pregnancies in which coumarin derivatives were used, one-sixth resulted in abnormal liveborn infants, one-sixth in abortion or stillbirth and, at most, two-thirds in apparently normal infants. In addition to the expected hemorrhagic complications, fetal effects of coumarin derivative administration include a specific embryopathy and central nervous system abnormalities. All available cases (including unpublished ones) of warfarin embryopathy and central nervous system abnormalities following gestational exposure to coumarin derivatives are reviewed, various complications are tabulated, critical periods of teratogenesis are discussed and possible mechanisms proposed. The use of heparin during gestation does not result in a significantly better outcome of pregnancy. In 135 published cases, the infants in one-eighth were stillborn, in one-fifth premature (a third of whom died) and, again at most, in two-thirds apparently normal. Because of the substantial risks of both clases of anticoagulants, and the inherent risks of pregnancy complicated by the indications for anticoagulation, prevention of pregnancy is usually indicated. If pregnancy occurs, a relatively normal outcome can be anticipated in about two-thirds of the pregnancies regardless of the anticoagulant used. Heparin does not appear to be a clearly superior alternative to coumarin derivatives.

Topics: Abnormalities, Drug-Induced; Adult; Central Nervous System; Chondrodysplasia Punctata; Coumarins; Female; Fetal Death; Fetal Diseases; Gestational Age; Hemorrhage; Heparin; Humans; Infant, Newborn; Male; Nose; Pregnancy; Pregnancy Complications, Cardiovascular; Risk; Syndrome

Topics: Abnormalities, Drug-Induced; Adult; Anticonvulsants; Epilepsy, Tonic-Clonic; Female; Fetus; Humans; Infant, Newborn; Macroglossia; Nose; Phenobarbital; Phenytoin; Pregnancy; Pregnancy Complications; Psychomotor Disorders; Skull; Toes

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

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

Mycophenolate mofetil has been shown to have teratogenic properties in animal studies and clinical reports. We report a case of major fetal malformation likely caused by mycophenolate mofetil exposure in utero in a 36 year old patient with systemic lupus erythematosus. The diagnosis was made by ultrasonography at 22 weeks of gestation.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adult; Ear, External; Facies; Female; Fetus; Humans; Imaging, Three-Dimensional; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Nose; Pregnancy; Pregnancy Complications; Ultrasonography, Prenatal

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

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; Adult; Anticoagulants; Chondrodysplasia Punctata; Female; Femur; Fetal Death; Fetal Growth Retardation; Gestational Age; Humans; Male; Nose; Pregnancy; Syndrome; Ultrasonography, Prenatal; Warfarin

The purpose of the present study was a 2D-semiautomated morphometric analysis of craniofacial growth in nuclear magnetic resonance imaged (NMRI) mouse embryos.. The NMRI mouse embryos were exposed in utero to either a single dose of 2 Gy X-irradiation on day 9 of gestation (113 embryos) or to 1.5 mg methyl-triazene administered orally to their pregnant mothers on gestational day 10.5 (124 embryos). An additional group of 108 embryos was used as controls. Digitized pictures of embryos from gestational days 14 to 17 were taken in lateral right view using a video system. Landmarks were located and digitized for computerized analysis of growth changes in relation to developmental stages of the face.. The results revealed that the snout of control embryos lengthens during the developmental period considered. The snout of embryos previously submitted to methyl-triazene displayed micrognathia, and all treated fetuses exhibited macroscopic signs of microcephaly with a reduced mandible. The snouts of irradiated embryos appeared shortened at the 14-day stage and continued to shorten as development proceeded. A shortening of the midface was detected macroscopically in 83% of the cases.. The results of this morphometric analysis enabled us to trace the developmental progression of the induced dysmorphosis and to assess the differences compared with normal development.

Topics: Abnormalities, Drug-Induced; Abnormalities, Radiation-Induced; Administration, Oral; Animals; Cephalometry; Cobalt Radioisotopes; Embryonic and Fetal Development; Face; Facial Bones; Female; Gestational Age; Image Processing, Computer-Assisted; Mandible; Maternal-Fetal Exchange; Mice; Microcephaly; Micrognathism; Nose; Particle Accelerators; Pregnancy; Radiation Dosage; Radiopharmaceuticals; Skull; Triazenes; Videotape Recording

A case of Warfarin embryopathia is shown. The newborn, whose mother had been treated with Marcoumar (Phenprocoumon 3 mg/day) during the whole pregnancy because of a hereditary protein-S-deficiency showed the typical symptom of nasal hypoplasia. Coumarol derivates pass the placental membrane and are known as teratogenic. Recent retrospective and prospective studies show that the risk of fetal or embryonal teratogenic injury is about 25-30% if Coumarol derivates are given through the 6th to the 9th week of pregnancy. It is possible to nearly avoid those injuries when Heparin is used for anticoagulant therapy in this period and Coumarol itself is used in the lowest possible therapeutic dose.

Topics: Abnormalities, Drug-Induced; Female; Glycoproteins; Humans; Infant, Newborn; Nose; Phenprocoumon; Pregnancy; Pregnancy Complications, Hematologic; Protein S; Risk Factors; Thrombophlebitis

Treatment of pregnant Sprague-Dawley rats with etretinate or retinoic acid on pregnancy days 8.5-9.0 resulted in craniofacial defects in all embryos. A morphological investigation of the malformations occurring in the nasal region is described. The external nose was deformed with a depressed nasal bridge and pronounced hump. Fusion between nasal processes was defective, resulting in fistulas and clefts. The nasal septal cartilage was reduced in size, the paranasal cartilage was missing, the parietothecal cartilage was deformed and the paraseptal cartilage was dislocated. Aberrant vessels were seen on the external nose in combination with underdevelopment of the vibrissae. The distance between the outer nasal pores was reduced after administration of retinoids.

Topics: Abnormalities, Drug-Induced; Animals; Embryo, Mammalian; Etretinate; Female; Nose; Pregnancy; Rats; Rats, Inbred Strains; Tretinoin

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

Salicylates are teratogens in animals, but their teratogenicity in man remains controverted. The possibility that massive oral intake in the first 3 months of pregnancy may induce malformations has not been eliminated. We report a second case of cyclopia associated with daily maternal ingestion of up to 4 g of acetylsalicylic acid in the first trimester.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Aspirin; Brain; Female; Humans; Infant, Newborn; Male; Nose; Orbit; Pregnancy; Pregnancy Trimester, First

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

The morphogenesis of median facial clefts induced in mice by treatment with diazo-oxo-norleucine (DON) was studied. Following maternal treatment with 0.4 mg/kg DON on the 11th gestational day, 23.1% of fetuses recovered at the 18th day exhibited median facial clefts, which were characterized by a separation in the midline of normal midfacial components, i.e., the premaxilla, nasal bones, and nasal capsule. Malformed embryos could first be identified grossly 24 hr after DON administration by the presence of an abnormally wide separation between the two narrowed medial nasal processes. Evidence of cellular degeneration was observed in the mesenchyme of the nasal processes of DON-treated embryos 8 and 12 hr after treatment, but little or no pyknotic debris remained at 24 hr post-injection. Loss of cells due to cell death was reflected in decreased cell density observed in all areas of facial mesenchyme examined 24 hr after DON administration. It is suggested that DON-induced median facial clefts may be caused by a reduction in tissue volume, particularly in the midline, or by an interference with normal facial growth resulting in increased facial width and consequent failure of merging of the medial nasal processes.

Topics: Abnormalities, Drug-Induced; Animals; Azo Compounds; Cell Division; Cleft Lip; Cleft Palate; Diazooxonorleucine; Face; Female; Mice; Mice, Inbred ICR; Nose; Pregnancy

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; Adolescent; Dwarfism; Epilepsy; Eye Abnormalities; Female; Fingers; Humans; Hydantoins; Nose; Pregnancy; Pregnancy Complications; Skull

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; Humans; Infant, Newborn; Male; Nose; Syndrome; Warfarin

A case is presented of fetal teratogenic damage from an unusually high maternal dosage of diphenylhydantoin, 600 mg daily, to a 40-kg woman throughout pregnancy. The anomalies included narrowed ends of the fingers and toes; aplasia of the nails on the other fingers and toes; aplasia of the distal phalanges of the fingers and toes; a broad, depressed nasal bridge; anteverted nostrils; prominent upper lip; coarse, profuse scalp hair; pilonidal sinus; and simian crease of the left hand. At the age of 7 months, ossification of the distal phalanges of both middle fingers appeared, the anterior fontanel was small, brain development was retarded, cranial asymmetry was marked, and the fingertips showed a pattern of low arch dermal ridges.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adult; Female; Fingers; Humans; Infant; Infant, Newborn; Lip; Male; Nails, Malformed; Nose; Phenytoin; Pregnancy; Thumb; Toes

Three small infants whose mothers had received oral anticoagulant therapy during the first trimester of pregnancy are described. These infants all had hypoplasia of the nasal bones, and two had stippling of epiphyses and bones and deformities of the bones of the hand. One child is mentally retarded. It is suggested that these abnormalities may be related to maternal oral anticoagulant therapy during the first trimester.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Adult; Anticoagulants; Aortic Valve; Carpal Bones; Chondrodysplasia Punctata; Face; Female; Foot; Hand; Hand Deformities, Congenital; Heart Valve Prosthesis; Humans; Infant, Newborn; Male; Maternal-Fetal Exchange; Mitral Valve; Nasal Bone; Nose; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Radiography

Pregnant Sprague-Dawley rats, a fed a rapeseed protein diet (containing 0.2 mg glucosinolates/g protein concentrate) from day 0, showed no teratological effects on the 18th day. However, rats which were permitted to deliver, developed anorexia and weight loss after day 18. A reddish discharge, not blood, from the nose stained the fur of most animals fed rapeseed protein. A similar discharge developed in dams fed on lab chow but fasted after day 18. At delivery, dams would neglect the newborn during the first 24 h but would then resume their diet and litter care. Surviving litters of rapeseed-fed animals were comparable to controls in weight after 3 weeks. Vitamin supplementation did not prevent these effects. Force feeding the diet by gavage aggravated these toxic effects and prolonged the gestation period. No toxic effects were seen until day 18 of gestation when the rapeseed protein diet was fed to rats 3--6 weeks before mating. Control rats given glucosinolates by gavage did not show any adverse effects. The rapeseed protein diet had no effect on NMRI mice during pregnancy and on litter care up to 3 weeks.

Topics: Abnormalities, Drug-Induced; Animals; Anorexia; Body Weight; Caseins; Dietary Proteins; Eye; Female; Growth; Mice; Nose; Plant Proteins; Pregnancy; Rats; Seeds; Teratogens

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Abnormalities, Severe Teratoid; Brain; Cortisone; Eye Abnormalities; Facial Bones; Female; Humans; Infant, Newborn; Male; Nose; Pregnancy; Pregnancy Complications, Infectious; Salicylates; Virus Diseases

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Child; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 16-18; Congenital Abnormalities; Deafness; Down Syndrome; Ear; Ear, External; Hepatitis; Humans; Larynx; Male; Mutation; Nose; Thalidomide; Trisomy

Topics: Abnormalities, Drug-Induced; Animals; Animals, Newborn; Cyclophosphamide; Ear; Forelimb; Mice; Nose

Topics: Abnormalities, Drug-Induced; Abnormalities, Severe Teratoid; Animals; Antineoplastic Agents; Cyclophosphamide; Face; Female; Gestational Age; Hydroxamic Acids; Hydroxyurea; Jaw Abnormalities; Limbic System; Mercaptopurine; Nitroso Compounds; Nose; Pregnancy; Rats

Topics: Abnormalities, Drug-Induced; Animals; Cleft Lip; Female; Folic Acid Antagonists; Lip; Male; Maxilla; Methane; Morphogenesis; Nose; Pregnancy; Rats; Salicylates; Trypan Blue

Topics: Abnormalities, Drug-Induced; Animals; Brain; Embryo, Mammalian; Incisor; Mice; Nose; Tooth Abnormalities; Vitamin A

Topics: Abnormalities, Drug-Induced; Child; Cleft Palate; Congenital Abnormalities; Female; Goiter; Hearing Disorders; Hearing Tests; Humans; Hyperbilirubinemia, Hereditary; Infant; Infant, Newborn; Iris; Kernicterus; Lacrimal Apparatus; Mandibulofacial Dysostosis; Measles; Meningoencephalitis; Mumps; Nose; Nose Deformities, Acquired; Osteogenesis Imperfecta; Otitis Media; Pierre Robin Syndrome; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Rubella; School Health Services; Toxicology; Waardenburg Syndrome