salicylates and Abnormalities--Drug-Induced

Dermatologists frequently are consulted by a pregnant patient or a woman of childbearing age who desires acne therapy. Because there are no published studies in which women took acne medications throughout pregnancy, information about safety must be obtained indirectly from studies in which the agents were taken for another indication during some portion of pregnancy. Oral tetracycline is associated with maternal liver toxicity and deciduous tooth staining in the infant, and tetracycline occasionally has been associated with other congenital anomalies. Maternal isotretinoin ingestion is associated with major craniofacial and cardiac deformities, as well as other congenital anomalies. Erythromycin, however, appears to be safe. Topical acne medications never have been implicated as a cause of fetal deformities in human beings. Dermatologists should be aware of potential toxic and teratogenic effects of acne medicines before prescribing them to women of childbearing age. Prompt reporting of adverse effects is encouraged.

Topics: Abnormalities, Drug-Induced; Acne Vulgaris; Administration, Cutaneous; Administration, Oral; Benzoyl Peroxide; Clindamycin; Erythromycin; Female; Humans; Pregnancy; Pregnancy Complications; Salicylates; Tetracyclines; Tretinoin

Drug effects on fetal physiology as well as possible teratogenesis need to be considered before prescribing for women of child-bearing age. All nonsteroidal anti-inflammatory drugs (NSAIDs), because of their suppression of prostaglandin synthesis, may prolong gestation and labour. Aspirin is also associated with an increased risk of ante- and post-partum haemorrhage. Indomethacin may be teratogenic in humans and like aspirin may induce pulmonary hypertension in the neonate. To reduce the physiological alterations induced by NSAIDs, short-half-life drugs such as ibuprofen, flurbiprofen or ketoprofen should be used at the maximally tolerable dosage interval. Gold salts and corticosteroids show little human evidence of teratogenicity although the largest possible dosage interval of gold should be used. D-Penicillamine may be teratogenic thus it should not be commenced during pregnancy and if a patient becomes pregnant whilst receiving the drug, it should be slowly withdrawn or the dosage reduced. 4-Aminoquinoline compounds are contra-indicated in pregnancy.

Topics: Abnormalities, Drug-Induced; Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Chloroquine; Female; Fetal Diseases; Gold; Humans; Indomethacin; Infant, Newborn; Penicillamine; Pregnancy; Pregnancy Complications; Rheumatic Diseases; Salicylates

Topics: Abnormalities, Drug-Induced; Adult; Aged; Anti-Inflammatory Agents; Central Nervous System; Child, Preschool; Drug Interactions; Eye; Humans; Male; Meningitis, Aseptic; Salicylates; Urogenital System

Topics: Abnormalities, Drug-Induced; Acetaminophen; Adrenal Cortex Hormones; Autoimmune Diseases; Azathioprine; Female; Fetus; Humans; Immunosuppressive Agents; Indomethacin; Infant, Newborn; Pregnancy; Pregnancy Complications; Salicylates

Salicylates have been the most widely studied of the nonnarcotic analgesics in pregnancy, and in the last 20 years evidence has accumulated indicating that their ingestion in pregnancy may have adverse effects on the mother and her child. Salicylates have been found to reduce the mean birth weight of the offspring in animal studies and in 1 human study. In the third trimester of pregnancy the maternal and fetal effects are mediated through the antiprostaglandin properties of salicylates and include prolongation of gestation and labor, increased blood loss at delivery, and increased perinatal mortality. Bleeding manifestations and withdrawal symptoms in newborn infants are associated with raised fetal blood salicylate levels. These effects of salicylates warrant routine antenatal urinary screening for salicylates in communities known to use them heavily. Adverse maternal or fetal effects form acetaminophen use in pregnancy have not been reported, but formal clinical or epidemiologic studies of its use have not been conducted.

Topics: Abnormalities, Drug-Induced; Acetaminophen; Animals; Birth Weight; Chemical and Drug Induced Liver Injury; Female; Fetal Blood; Fetal Growth Retardation; Fetus; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver; Obstetric Labor Complications; Pregnancy; Pregnancy, Prolonged; Retrospective Studies; Salicylates

Topics: Abnormalities, Drug-Induced; Amino Acids; Anti-Bacterial Agents; Atmosphere; Carbon Dioxide; Culture Media; Drug Evaluation, Preclinical; Fertilization; Fetus; Fingers; Folic Acid Deficiency; Hormones; Humans; Hydrogen-Ion Concentration; Immune Sera; Immunosuppressive Agents; Organ Culture Techniques; Oxygen; Salicylates; Temperature; Teratogens; Thalidomide; Vitamin A Deficiency; Vitamin E Deficiency; Vitamins

Topics: Abnormalities, Drug-Induced; Alkylating Agents; Animals; Anticonvulsants; Antimetabolites; Central Nervous System; Chromosome Aberrations; Chromosome Disorders; Disease Models, Animal; DNA; Drug Evaluation; Drug Evaluation, Preclinical; Drug Labeling; Female; Gestational Age; Hormones; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Salicylates; Substance Withdrawal Syndrome; Thalidomide; United States; United States Food and Drug Administration

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Antineoplastic Agents; Female; Gestational Age; Humans; Infant, Newborn; Maternal-Fetal Exchange; Mercury Poisoning; Mutation; Norethindrone; Phenmetrazine; Pregnancy; Reserpine; Salicylates; Sulfonamides

Topics: Abnormalities, Drug-Induced; Adrenal Cortex Hormones; Anti-Bacterial Agents; Anticoagulants; Antineoplastic Agents; Antithyroid Agents; Barbiturates; Breast Feeding; Contraceptives, Oral; Diethylstilbestrol; Drug-Related Side Effects and Adverse Reactions; Female; Fetal Death; Fetus; Humans; Hypoglycemic Agents; Infant, Newborn; Lactation; Maternal-Fetal Exchange; Meprobamate; Molecular Weight; Nicotine; Nitrofurantoin; Permeability; Placenta; Pregnancy; Quinine; Reserpine; Salicylates; Sulfonamides

Topics: Abnormalities, Drug-Induced; Alkylating Agents; Analgesics; Animals; Aspirin; Carcinogens; Drug-Related Side Effects and Adverse Reactions; Hexachlorophene; Humans; Hydrazines; Isoniazid; Phenacetin; Phenylbutazone; Phenytoin; Procarbazine; Salicylates

Topics: Abnormalities, Drug-Induced; Adult; Animals; Animals, Newborn; Anti-Bacterial Agents; Antineoplastic Agents; Carcinogens; Cats; Female; Fetus; Humans; Hypnotics and Sedatives; Infant, Newborn; Mice; Pregnancy; Pregnancy, Animal; Rabbits; Rats; Salicylates; Steroids; Tranquilizing Agents

Topics: Abnormalities, Drug-Induced; Animals; Blood Vessels; Carbohydrate Metabolism; Female; Glycosaminoglycans; Mice; Musculoskeletal System; Pharmacology; Pregnancy; Pregnancy, Animal; Research; Salicylates; Skeleton; Teratogens

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

Gastroschisis, which is a defect in the abdominal wall, lateral to the umbilical cord, is considered to be a vascular problem, probably due to a disruption of the omphalomesenteric artery [Hoyme et al. (1981) J. Pediatr. 98:228-231]. Recently, Torfs et al. [(1996) Teratology 54:84-92] observed a significantly increased risk for aspirin and ibuprofen, two strong cyclooxygenase inhibitors. Here we present the results of a case-control study conducted by the Spanish Collaborative Study of Congenital Malformations (ECEMC) on the relationship between prenatal exposure to salicylates during the first trimester of pregnancy and gastroschisis. The results show an increased risk (OR = 3.47; P = 0.015) after controlling the possible effect of maternal age and maternal smoking during pregnancy.

Topics: Abdominal Muscles; Abnormalities, Drug-Induced; Adult; Case-Control Studies; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Risk; Salicylates; Spain

This study examined the pharmacokinetics and potential teratogenicity of the nonsteroidal antiinflammatory drug, diflunisal, in cynomolgus monkeys. Pregnant cynomolgus monkeys were administered 0.5% methyl cellulose, 20 mg/kg/day diflunisal, or 80 mg/kg/day diflunisal on Days 25 to 48 of gestation. There was no evidence of maternal toxicity, increased abortion rate, fetal growth retardation, or malformation. These data demonstrate that diflunisal is not teratogenic in cynomolgus monkeys over a dosage range of 20 to 80 mg/kg/day. Peak plasma levels of diflunisal were found 1 hr after oral administration of [14C]diflunisal at a dosage of 60 mg/kg and declined to low levels by 24 hr. The plasma elimination half-life was calculated to be 10.2 hr over the period of 1 to 8 hr postadministration. Intact diflunisal accounted for 96.4% of total plasma radioactivity at 0.5 hr and declined to a value of 74% at 8 hr. Plasma protein binding averaged greater than 99% over a concentration range of 62.5 to 250 micrograms/ml. Urinary excretion of diflunisal and metabolites averaged 66.5% of the dosage over the first 4 days postadministration, compared with 0.8% in the feces. The majority of activity represented conjugates of diflunisal. Embryo concentrations of diflunisal on Days 35 to 37 of gestation were 0.7 and 1.1% of maternal plasma level at 4 hr postadministration of 20 or 60 mg/kg, respectively.

Topics: Abnormalities, Drug-Induced; Animals; Diflunisal; Dose-Response Relationship, Drug; Embryo, Mammalian; Female; Fetus; Half-Life; Humans; Kinetics; Macaca fascicularis; Pregnancy; Salicylates; Species Specificity

Comparisons were made of rat embryos cultured at 5% or 20% oxygen in the presence of salicylate (SAL), cyclophosphamide (CP), niridazole (NDZ), or phosphoramide mustard (PM). Multiple regression analyses were used to compare the effects of drug concentration, oxygen concentration, and the product of drug times oxygen concentration on malformation incidence, viability, and protein content of embryos cultured for 24 hours. Drug concentration significantly affected malformation incidence or severity and protein content (P less than 0.001) for the four drugs tested. Oxygen concentration significantly affected protein content for the four compounds (P less than 0.001) but affected malformation incidence only with NDZ. Furthermore, the interaction of oxygen concentration and drug concentration significantly affected the malformation incidence in the presence of NDZ (P less than 0.001), and protein content (P less than 0.001) and viability (P less than 0.001) in the presence of CP. The pattern of significant effects of the independent variables (drug concentration, oxygen concentration, and drug times oxygen concentration) is consistent with the hypotheses of oxygen-dependent metabolism (or lack of metabolism) of the drugs in question. NDZ, which is thought to be converted to reactive intermediates by an oxygen-inhibited nitroreductase, was more toxic at reduced oxygen tension. CP, which is activated by an oxygen-dependent P-450 system, was more toxic with increased oxygen tension. Significant effects of the independent variables on embryos exposed to SAL or PM were consistent with the effects on control embryos, notably, increased protein content with increased oxygen.

Topics: Abnormalities, Drug-Induced; Aerobiosis; Animals; Cyclophosphamide; Embryo, Mammalian; Embryonic and Fetal Development; Female; Niridazole; Organ Culture Techniques; Oxygen; Phosphoramide Mustards; Pregnancy; Proteins; Rats; Rats, Inbred Strains; Regression Analysis; Salicylates; Salicylic Acid; Teratogens

Prescription data for the three months before the last menstrual period and for the first trimester of pregnancy were obtained for 764 mothers whose children had a defect of the central nervous system and for an equal number of mothers of control babies born from the same doctors' practices. There was a statistically significant difference overall between the numbers of mothers who were prescribed drugs in the study and control groups during the trimester before the last menstrual period but no such difference was found for the first pregnancy trimester, nor was there a significant difference for any specific group of drugs. For a composite group of non-steroid anti-inflammatory drugs, salicylates, and sulphasalazine there was a significant difference for the trimester before the last menstrual period. There are arguments against such an artificial grouping, however, and when the individual drugs were considered the comparisons were no longer significant. The odds ratios for all medicines containing folic acid taken in the trimester before the last menstrual period were considerably less than unity, in contrast with nearly all other comparisons. This supports a suggested protective effect against neural tube defects of folic acid supplements begun before the onset of pregnancy but the odds ratios of these comparisons were not statistically significant.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adolescent; Adult; Anti-Inflammatory Agents; Female; Folic Acid; Humans; Maternal Age; Middle Aged; Neural Tube Defects; Pregnancy; Pregnancy Trimester, First; Salicylates; Sulfasalazine

Rat embryos were exposed to aspirin or its metabolite, salicylic acid in culture. In these embryos acute reduction of heart beat was observed during 4 hours of administration compared to that in non-treated one. Protein contents and crown-rump length of cultured embryos were significantly decreased in aspirin-treated group, but were not so decreased in salicylic acid-treated one. The predominant defects of the embryos exposed to aspirin were edematous facial malformations and abnormality of tail. On the other hand, facial anomalies such as cleft lip and curly tail were observed in the embryos cultured with salicylic acid. Anomalies induced by aspirin were systemic, while salicylic acid induced localized malformations. These results might be due to the differences between aspirin and its metabolite, salicylic acid in their teratogenicity.

Topics: Abnormalities, Drug-Induced; Animals; Aspirin; Embryo, Mammalian; Female; Organ Culture Techniques; Pregnancy; Rats; Rats, Inbred Strains; Salicylates

Diflunisal [5-(2,4-difluorophenyl)-salicylic acid] is a new analgesic antiinflammatory drug that, when administered orally to rabbits at 40 and 60 mg/kg/day, caused terata, most commonly axial skeletal defects. These same dosage levels also caused a severe maternal hemolytic anemia following a dramatic decrease in erythrocyte ATP levels. The teratogenicity, anemia, and depletion of ATP were unique to the rabbit among species examined. To test the possible causality between the teratogenic effects and anemia induced by diflunisal, a single dose of 180 mg/kg diflunisal was administered to rabbits on gestation day 5. This treatment produced an anemia that persisted through gestation day 15 in addition to causing the characteristic axial skeletal defects. Since diflunisal was cleared from maternal blood before gestation day 9, the critical day for induction of similar axial skeletal defects by hypoxia, the skeletal malformations probably resulted from maternal hypoxia secondary to anemia and not from a direct and specific effect of the drug on the embryo. In addition, we observed that the diflunisal level in the embryo was less than 5% of the peak maternal blood level probably as a result of high plasma protein binding of diflunisal in the maternal blood (greater than 98%). This relatively low placental transfer may explain the lack of diflunisal teratogenicity in rats and mice compared to aspirin which crosses the placenta more readily. These studies demonstrate that a species that exhibits unusually severe drug-specific maternotoxicity is probably an unsuitable model for the prediction of the teratogenic potential of that drug in humans.

Topics: Abnormalities, Drug-Induced; Adenosine Triphosphate; Anemia, Hemolytic; Animals; Antioxidants; Aspirin; Diflunisal; Erythrocytes; Female; Gestational Age; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Hematologic; Rabbits; Rats; Rats, Inbred Strains; Salicylates

The influence of dietary zinc concentration on salicylate teratogenesis was studied in Wistar and Sprague-Dawley rats. Females were fed purified diets containing 0.4, 4.5, 9, 100, or 1,000 micrograms zinc/gm diet, or a stock diet (Purina Rat Chow) from day zero to day 21 of gestation, when they were killed and the fetuses were examined. On day 9, rats were given saline or 250, 500, or 750 mg sodium salicylate/kg body weight by gavage. Increasing drug dose caused increased frequency of malformed or resorbed fetuses, while increasing dietary zinc reduced the teratogenic effects of salicylate, but in different patterns in the two strains. The teratogenic effect of zinc deficiency also varied by strain. Statistical analysis showed that the frequency of malformed fetuses was significantly affected by levels of dietary zinc or salicylate dose, and interactions of zinc X salicylate and genetic strain X zinc. Frequency of resorption was affected by strain, zinc, salicylate, and interactions of strain X salicylate, zinc X salicylate, and strain X zinc X salicylate. Frequency of abnormal sites (malformed or resorbed) was affected by strain, zinc, salicylate, and interactions of strain X salicylate, zinc X salicylate, and strain X zinc X salicylate. The results suggest that marginal zinc deficiency in certain pregnant women might increase the possibility of salicylate teratogenicity.

Topics: Abnormalities, Drug-Induced; Animals; Diet; Drug Interactions; Female; Fetal Resorption; Pregnancy; Rats; Rats, Inbred Strains; Salicylates; Statistics as Topic; Zinc

The three major metabolites of salicylate, o- hydroxyhippurate ( salicylglycine , salicyluric acid), 2,5-dihydroxybenzoate (gentisic acid), and 2,3-dihydroxybenzoate, were examined for their capacities to elicit dysmorphogenesis, embryolethality , and growth retarding effects in an embryo culture system. The effects were compared with those produced by the parent salicylate. At the highest concentrations tested (1.9 mM), none of the three metabolites produced significant increases in the number of malformed embryos or in embryolethality . At the same concentration, all three agents reduced crown-rump lengths and somite numbers slightly but significantly (p less than 0.01), and the dihydroxy metabolites also reduced the embryonic protein content (p less than 0.01). In contrast, the parent salicylate produced large increases in embryolethality ( embryolethality in controls was 6% or less) and malformed embryos at equivalent or lower concentrations. Preincubation of the parent salicylate with various biotransforming systems did not affect embryotoxicity significantly. The most rapid biotransformation of salicylate in vitro was achieved with mitochondrial preparations of monkey kidney as the enzyme source but quantities metabolized were not sufficient to prevent malformations in the culture system. Increased serum protein concentration in the culture medium, however, markedly reduced the capacity of added salicylate to cause malformations. An examination of the kinetics of the dysmorphogenic effects of parent salicylate indicated that 5 hr of exposure elicited nonsignificant increases in numbers of malformations. A significant malformation rate was produced by 9 hr of exposure. In contrast, effects on embryonic growth parameters and embryolethality were greatest after a 24-hr exposure period. The results strongly suggest that the parent salicylate, rather than generated metabolites, was primarily or solely responsible for the malformations observed and that the duration of exposure of embryos to unmetabolized salicylate may be the critical factor for determining teratogenic outcome.

Topics: Abnormalities, Drug-Induced; Animals; Biotransformation; Blood Proteins; Embryo, Mammalian; Female; Pregnancy; Protein Binding; Rats; Rats, Inbred Strains; Salicylates; Species Specificity

Topics: Abnormalities, Drug-Induced; Animals; Behavior; Caffeine; Female; Food Additives; Food Supply; Humans; Nervous System; Pregnancy; Rats; Salicylates; United States; United States Food and Drug Administration

CFY rats were exposed to inhalation of fresh air at days 10-13 of gestation; at day 12 the dams were given 0, 125, 250, 500, or 1,000 mg/kg acetylsalicylic acid (ASA) by gavage. During the same period of gestation (days 10-13) further groups of rats were exposed to toluene at 1,000, 2,000, and 3,600 mg/m3 atmospheric concentration and were given 250 mg/kg ASA by gavage; two subgroups of animals treated with 250 mg/kg ASA in combination with 3,600 mg/m3 toluene inhalation were given 0, 2.5, or 5 gm/kg glycine 2 hours before the ASA dose. At day 21 the animals were killed and examined for teratogenic effects and histological changes. After 48 hours toluene exposure other groups of rats were treated with ASA or with ASA plus glycine (administered 2 hours earlier) on day 20 of gestation. These animals were killed 2 hours later and the salicylic acid concentration in maternal and embryonic plasma and in amniotic fluid was measured by gas chromatography. With the rising ASA doses both maternal toxicity (increased mortality, decreased food consumption, and weight gain) and embryonic toxicity (postimplantation loss, increased incidence of weight-retarded fetuses, increased minor anomalies and malformations, decreased average weight of fetuses) increased. Toluene was found to potentiate the toxic effect of ASA and to increase both maternal and embryonic toxicity. The type of ASA-induced minor anomalies and malformations was also found to be altered under the effect of toluene pretreatment. By raising the toluene concentration the salicylic acid level in the maternal and embryonic plasma and in the amniotic fluid was increased above the expected concentration. The mechanism of the potentiating interaction should be looked for in the depletion of the glycine pool by toluene (and its metabolites) and in the resultant increase of salicylic acid level. Increasing ASA embryotoxicity caused by toluene can be warded off by glycine administration.

Topics: Abnormalities, Drug-Induced; Amniotic Fluid; Animals; Aspirin; Drug Interactions; Embryo, Mammalian; Female; Gestational Age; Glycine; Pregnancy; Rats; Salicylates; Salicylic Acid; Teratogens; Toluene

The mechanism for the enhancing effect of pyrogen (lipopolysaccharide, LPS) on the fetal toxicity of acetylsalicylic acid (ASA) was studied in pregnant rats. The lethality of ASA was significantly enhanced by LPS in male rats. The fetal toxicity of ASA including fetal death, resorption, growth retardation, and skeletal anomalies (wavy rib and asymmetry of sternebra) was slightly observed in the dams that received a single dose of ASA (125 to 500 mg/kg, p.o.) on the 15th day of gestation, but it was markedly increased by LPS (20 micrograms/kg, i.v.). The enhancement of the toxicity of ASA by LPS was also observed in the maternal body weight gain until term. The plasma concentrations of ASA and salicylic acid (SA), the major metabolite of ASA, were increased by LPS. The tissue concentrations of SA were also increased in the following order: placenta, brain, fetus, uterus, liver and kidney. The ATP levels of placenta and fetus were not influenced by ASA alone, but markedly decreased by both LPS and ASA.

Topics: Abnormalities, Drug-Induced; Adenosine Triphosphate; Animals; Aspirin; Body Weight; Drug Synergism; Female; Fetus; Humans; Infant, Newborn; Lipopolysaccharides; Male; Maternal-Fetal Exchange; Pregnancy; Pyrogens; Rats; Salicylates; Salicylic Acid; Tissue Distribution

Topics: Abnormalities, Drug-Induced; Animals; Female; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, Ancient; Humans; Illicit Drugs; Infant, Newborn; Male; Mercury; Pregnancy; Salicylates; Thalidomide

Topics: Abnormalities, Drug-Induced; Eye Abnormalities; Female; Humans; Pregnancy; Salicylates

Seven litters and 17 near-term rats of mothers treated with teratogens during gestation were analyzed for concordance and discordance of congenital malformations of the central nervous system. In animals with spina bifida a firm association with Arnold-Chiari malformation was found but only in fetuses near term. Associations with aqueduct stenosis and hydrocephalus were poor. In general, the findings support the theory that the components of the spina bifida complex develop from a common teratogenic disturbance but independent from each other.

Topics: Abnormalities, Drug-Induced; Animals; Arnold-Chiari Malformation; Cerebral Aqueduct; Hydrocephalus; Rats; Salicylates; Spina Bifida Occulta; Trypan Blue

Topics: Abnormalities, Drug-Induced; Animals; Female; Humans; Infant, Newborn; Pregnancy; Salicylates

Prostaglandin F2 alpha alone and in combination with sodium salicylate, was administered i.m. to pregnant CBA mice at various times on day 9 of gestation. A high frequency of rib malformations (90%) was recorded whereas the resorption rate was moderate (18%). When combining prostaglandin treatment (25 mg/kg i.m.) with sodium salicylate (500 mg/kg i.m.), the resorption rate increased. The malformation frequency remained unchanged except for the group with combined treatment at 10 a.m. (=maximum teratogenic period for salicylate induced rib malformations). This treatment resulted in a high frequency of maternal death; the resorption frequency was 75% and the surviving foetuses were malformed.

Topics: Abnormalities, Drug-Induced; Animals; Cyclooxygenase Inhibitors; Female; Fetal Resorption; Fetus; Male; Mice; Mice, Inbred CBA; Pregnancy; Prostaglandins; Prostaglandins F; Ribs; Salicylates

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Abnormalities, Severe Teratoid; Adult; Female; Humans; Infant, Newborn; Male; Pregnancy; Salicylates; Teratogens

Topics: Abnormalities, Drug-Induced; Animals; Female; Ferrets; Fetus; Pregnancy; Rats; Salicylates; Species Specificity; Teratogens

The purpose of this paper is to review the development of the mammalian kidney and to assess the influence that various perinatal manipulations may have on the developmental process either morphologically or functionally. Immature kidneys in general have less functional capacity than adult kidneys and a low rate of glomerular filtration, perhaps related to renal blood flow, which appears to limit the disposition of a fluid or solute load. Tubular reabsorption is also limited leading to the urinary loss of glucose, amino acids, bicarbonate and phosphate. Although the relatively low function of the immature kidney is a normal part of development, its capacity to respond under conditions of stress may be less adequate than in adults. An additional concern is that a variety of perinatal manipulations, such as the incidental or accidental ingestion of a chemical, may lead to varying degrees of altered morphogenesis or functional development of the kidney. Chemical induced renal anomalies may be of several types, but in typical teratology experiments hydronephrosis may be the most frequent observation. The functional consequences of these renal malformations may be lethal or inconsequential or while an animal may be able to survive and develop normally in the presence of a renal malformation, it is possible that a stressful situation would unmask a functional malformation which could compromise survival. Thus, some renal abnormalities may be subtle enough to go unnoticed without experimental tests. Without such tests it is impossible to evaluate the effect of functional alterations on successful adaptation.

Topics: Abnormalities, Drug-Induced; Animals; Animals, Newborn; Dinitrophenols; Diphenylamine; Female; Guinea Pigs; Humans; Hydronephrosis; Infant, Newborn; Kidney; Kidney Diseases; Paraquat; Penicillins; Polychlorinated Dibenzodioxins; Polycystic Kidney Diseases; Pregnancy; Rabbits; Salicylates

Topics: Abnormalities, Drug-Induced; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Salicylates; Substance-Related Disorders

The linkage between potentially teratogenic factors was studied in a material of 599 children with oral clefts and their matched controls. A method based on Yule's Q coefficient describing the degree of association between two dichotomous variables was applied. All factors studied (five groups of drugs taken by the mothers during early pregnancy, maternal influenza and fever) were significantly associated with the birth of children with clefts. The only factor whose association with clefts was explained by linkage to other factors was fever. In addition, the association between clefts and antipyretic analgesics other than salicylates could be partly explained by controlling the intake of salicylates. Although there was a strong association between influenza and consumption of salicylates, the correlation of neither of the two factors with oral clefts could be even partly explained by controlling the other. The method is considered suitable for epidemiological studies of congenital defects.

Topics: Abnormalities, Drug-Induced; Analgesics; Child; Child, Preschool; Cleft Lip; Cleft Palate; Epidemiologic Methods; Female; Humans; Influenza, Human; Opium; Penicillins; Pregnancy; Pregnancy Complications, Infectious; Salicylates; Teratogens

Associations between drug consumption during pregnancy and the birth of children with oral clefts were studied in material from the Finnish Register of Congenital Malformations, consisting of 599 children with clefts and their matched controls. Information concerning maternal drug consumption was partly prospective. During the first trimester, analgesic, chemotherapeutic and antineurotic drugs had all been significantly more frequently used by the mothers of children with clefts, than by the control mothers. The consumption of drugs was in general more frequent among mothers of children with cleft lip, with or without cleft palate, than among those of children with cleft palate alone.

Topics: Abnormalities, Drug-Induced; Analgesics; Anticonvulsants; Chloramphenicol; Cleft Lip; Cleft Palate; Diazepam; Drug-Related Side Effects and Adverse Reactions; Female; Fetus; Finland; Humans; Insulin; Iron; Penicillins; Pregnancy; Pregnancy Trimester, First; Salicylates; Sulfonamides; Tetracycline; Vitamins

Asynchronous blastocyst transfer, supposed to equalize the developmental stage of native and alien embryos during the organogenic period, was used as a tool in a teratological investigation. A spurious protection by the transfer as such was shown to depend on a persisting asynchrony between native and alien foetuses. The initial difference of 24 h was not nullified, but decreased to 8 h. This difference allowed transferred foetuses to pass the period of maximum sensitivity before salicylate treatment.

Topics: Abnormalities, Drug-Induced; Animals; Crosses, Genetic; Embryo Transfer; Embryo, Mammalian; Female; Male; Mice; Mice, Inbred CBA; Mice, Inbred Strains; Ribs; Salicylates; Teratogens; Time Factors; Transplantation, Homologous

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Animals; Cell Membrane; Drug Interactions; Drug Synergism; Edema; Embryo Implantation; Esters; Female; Fetal Death; Glucuronidase; Hindlimb; Inflammation; Lysosomes; Male; Methanol; Mice; Nicotinic Acids; Pregnancy; Rats; Salicylates; Stimulation, Chemical

Topics: Abnormalities, Drug-Induced; Animals; Cyclophosphamide; Embryo, Mammalian; Fetus; Jaw; Jaw Abnormalities; Rats; Salicylates; Tooth Abnormalities

Topics: Abnormalities, Drug-Induced; Analgesics; Anti-Bacterial Agents; Bone and Bones; Central Nervous System; Congenital Abnormalities; Female; Finland; Humans; Hypnotics and Sedatives; Influenza, Human; Pregnancy; Pregnancy Complications, Infectious; Salicylates; Sulfonamides; Time Factors

Topics: Abnormalities, Drug-Induced; Animals; Chelating Agents; Cortisone; Female; Haplorhini; Humans; Phenytoin; Pregnancy; Salicylates; Vitamin B 12

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; Animals; Aspirin; Carbon Isotopes; Edetic Acid; Female; Fetus; Iron; Iron Isotopes; Manganese; Maternal-Fetal Exchange; Pregnancy; Radioisotopes; Rats; Salicylates; Time Factors; Zinc; Zinc Isotopes

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Anencephaly; Arm; Cleft Lip; Cleft Palate; Craniofacial Dysostosis; Drug Interactions; Female; Fetus; Fingers; Foot Deformities, Congenital; Gestational Age; Hand Deformities, Congenital; Heart Defects, Congenital; Humans; Infant, Newborn; Male; Maternal-Fetal Exchange; Metacarpus; Pregnancy; Salicylates; Thumb; Toes; Umbilical Cord; Urethra

Topics: Abnormalities, Drug-Induced; Animals; Autonomic Nervous System; Bicarbonates; Chlorpromazine; Embryonic and Fetal Development; Female; Immobilization; Phenobarbital; Pregnancy; Pressure; Rats; Reserpine; Salicylates; Uterine Hemorrhage; Uterus

Topics: Abnormalities, Drug-Induced; Acetazolamide; Animals; Bone and Bones; Dactinomycin; Dose-Response Relationship, Drug; Female; Genetic Variation; Maternal-Fetal Exchange; Pregnancy; Rats; Ribs; Salicylates; Spine; Sternum

Topics: Abnormalities, Drug-Induced; Central Nervous System; Female; Humans; Infant, Newborn; Influenza, Human; Pregnancy; Pregnancy Complications, Infectious; Salicylates

Topics: Abnormalities, Drug-Induced; Anesthesia, General; Anti-Bacterial Agents; Antiemetics; Congenital Abnormalities; Contraceptives, Oral; Female; Humans; Hypnotics and Sedatives; Iron; Pregnancy; Pregnancy Complications; Retrospective Studies; Salicylates; Smoking; Steroids; Sulfonamides; Teratogens; Time Factors; Wales

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Female; Fetal Diseases; Fetus; Gestational Age; Hydronephrosis; Injections, Intraperitoneal; Kidney; Maternal-Fetal Exchange; Organ Size; Pregnancy; Rats; Salicylates

Topics: Abnormalities, Drug-Induced; Animals; Female; Fetus; Glycogen; Liver Glycogen; Maternal-Fetal Exchange; Mice; Myocardium; Pregnancy; Salicylates; Species Specificity

Topics: Abnormalities, Drug-Induced; Animals; Carbon Isotopes; Female; Fetus; Liver; Maternal-Fetal Exchange; Mice; Pregnancy; Salicylates

Topics: Abnormalities, Drug-Induced; Animals; Aspirin; Benzoates; Biotransformation; Female; Fetal Death; Fetus; Gestational Age; Pregnancy; Rats; Salicylates

Topics: Abnormalities, Drug-Induced; Animals; Female; Fetal Death; Fetus; Nucleic Acids; Orotic Acid; Pregnancy; Rats; RNA Nucleotidyltransferases; Salicylates; Thymidine; Tritium

Topics: Abnormalities, Drug-Induced; Animals; Chemical and Drug Induced Liver Injury; Female; Fetal Death; Fetal Diseases; Gastrointestinal Hemorrhage; Gestational Age; Hemorrhage; Injections, Intramuscular; Liver; Mice; Pentobarbital; Pregnancy; Salicylates

Topics: Abnormalities, Drug-Induced; Aspirin; Central Nervous System; Clubfoot; Digestive System Abnormalities; Female; Gestational Age; Humans; Pregnancy; Salicylates

Topics: Abnormalities, Drug-Induced; Accidents; Congenital Abnormalities; Diet; Drug-Related Side Effects and Adverse Reactions; Environment; Family Characteristics; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Residence Characteristics; Salicylates; Socioeconomic Factors; Wales

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; Abnormalities, Multiple; Female; Humans; Infant, Newborn; Influenza, Human; Pregnancy; Pregnancy Complications, Infectious; Salicylates

Topics: Abnormalities, Drug-Induced; Adrenal Glands; Anencephaly; Animals; Female; Hydrocephalus; Pituitary Gland; Pregnancy; Pregnancy, Animal; Radiation Genetics; Rats; Salicylates; Streptonigrin; Trypan Blue; Vitamin A

Topics: Abnormalities, Drug-Induced; Animals; Aorta; Aspirin; Dextrocardia; Female; Fetal Heart; Gestational Age; Maternal-Fetal Exchange; Pregnancy; Rats; Salicylates; Transposition of Great Vessels

Topics: Abnormalities, Drug-Induced; Animals; Female; Fetal Death; Fetus; Mice; Pregnancy; Salicylates

Topics: Abnormalities, Drug-Induced; Animals; Female; Mice; Microradiography; Pregnancy; Pregnancy, Animal; Ribs; Salicylates; Skeleton; Spine

Topics: Abnormalities, Drug-Induced; Animals; Aspirin; Female; Pregnancy; Pregnancy, Animal; Rats; Salicylates

Topics: Abnormalities, Drug-Induced; Aspirin; Blood Vessels; Carbohydrate Metabolism; Glycosaminoglycans; Mice; Pharmacology; Pregnancy; Pregnancy, Animal; Research; Ribs; Salicylates; Salicylic Acid; Spine; Teratogens; Toxicology

Topics: Abnormalities, Drug-Induced; Autoradiography; Bone Development; Embryology; Epinephrine; Immobilization; Pregnancy; Pregnancy, Animal; Rats; Research; Reserpine; Salicylates; Sodium Salicylate; Teratogenesis; Teratogens; Toxicology

Topics: Abnormalities, Drug-Induced; Adrenalectomy; Ammonium Chloride; Animals; Cortisone; Dinitrophenols; Embryo, Mammalian; Embryo, Nonmammalian; Female; Histocytochemistry; Humans; Maternal-Fetal Exchange; Pregnancy; Pregnancy, Animal; Rats; Research; Salicylates; Toxicology; Water-Electrolyte Balance

Topics: Abnormalities, Drug-Induced; Central Nervous System Depressants; Chlorpromazine; Fetal Death; Immobilization; Pentobarbital; Pharmacology; Pregnancy; Pregnancy, Animal; Rats; Research; Salicylates; Sodium Salicylate; Toxicology

Topics: Abnormalities, Drug-Induced; Animals; Mice; Pathology; Research; Salicylates; Sodium Salicylate; Toxicology

Topics: Abnormalities, Drug-Induced; Animals; Female; Humans; Immobilization; Pharmacology; Pregnancy; Pregnancy, Animal; Rats; Research; Salicylates; Sodium Salicylate; Stress, Physiological; Toxicology