salicylates and Abnormalities--Multiple

Aspirin ingestion in humans and animals has been reported to lead to a range of undesirable outcomes, including fetal death, growth retardation, and congenital abnormalities. Rat embryos were cultured for 48 h in 100-300 micrograms/ml of salicylic acid, a metabolite of aspirin, days 9.5-11.5 of gestation. When compared to growth in control embryos, a significant dose-dependent decrease in crown-rump lengths, somite numbers, and yolk sac diameters was observed. There was also a significant increase in overall dysmorphology, including eye, brachial arch, and heart anomalies, and an absence of forelimb buds. The neural tube was especially vulnerable and had frequently failed to close. Cellular and ultrastructural examination revealed extensive cell death in the neuroepithelium, with a lesser effect on the mesenchymal cells. Large condensed blebs projected into the ventricular lumen, and cell membranes as well as the basal lamina were severely disrupted, with all cytoplasmic organelles affected in dying cells. It is likely that the extensive cell necrosis and blebbing in the developing neuroepithelium at the site of neural tube fusion may be involved in failed neurulation, while necrosis at other sites in the cranial neuroepithelium may be linked with previously reported intellectual and behavioural abnormalities.

Topics: Abnormalities, Multiple; Animals; Culture Techniques; Embryo, Mammalian; Face; Female; Heart Defects, Congenital; Microscopy, Electron; Nervous System; Rats; Rats, Sprague-Dawley; Salicylates; Salicylic Acid; Skull; 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

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

The babies of 144 mothers who took salicylates regularly in pregnancy are described. These babies had a significantly reduced birth-weight compared with controls; many of them had a raised cord-blood salicylate level but had no clinical evidence of bleeding or hypoglycaemia. Their perinatal mortality was increased, but the incidence of congenital anomalies was not significantly raised.

Topics: Abnormalities, Multiple; Birth Weight; Female; Fetal Death; Fetus; Gestational Age; Hand Deformities, Congenital; Heart Defects, Congenital; Hernias, Diaphragmatic, Congenital; Humans; Infant, Newborn; Intestinal Perforation; Male; Maternal-Fetal Exchange; Pregnancy; Salicylates

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