drug induced abnormalities


Summary: Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment.

Top Publications

  1. Chapin R, Adams J, Boekelheide K, Gray L, Hayward S, Lees P, et al. NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A. Birth Defects Res B Dev Reprod Toxicol. 2008;83:157-395 pubmed publisher
  2. Diav Citrin O, Shechtman S, Weinbaum D, Wajnberg R, Avgil M, Di Gianantonio E, et al. Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational study. Br J Clin Pharmacol. 2008;66:695-705 pubmed publisher
    ..66 (95% CI 0.80, 8.90) and 4.47 (95% CI 1.31, 15.27), respectively. This study suggests a possible association between cardiovascular anomalies and first-trimester exposure to fluoxetine. ..
  3. Sánchez S, Seltzer A, Fuentes L, Forneris M, Ciuffo G. Inhibition of Angiotensin II receptors during pregnancy induces malformations in developing rat kidney. Eur J Pharmacol. 2008;588:114-23 pubmed publisher
    ..These observations confirm previous assumptions that in the developing kidney Angiotensin II exerts stimulatory effects through AT(1) receptors that might be counterbalanced by angiotensin AT(2) receptors. ..
  4. Kallen B, Otterblad Olausson P. Antidepressant drugs during pregnancy and infant congenital heart defect. Reprod Toxicol. 2006;21:221-2 pubmed
  5. Berard A, Ramos E, Rey E, Blais L, St André M, Oraichi D. First trimester exposure to paroxetine and risk of cardiac malformations in infants: the importance of dosage. Birth Defects Res B Dev Reprod Toxicol. 2007;80:18-27 pubmed
    ..07, 95% CI = 1.00, 9.42). Gestational exposure to paroxetine is associated with major congenital malformations and major cardiac malformations for only first trimester exposure above 25 mg/day. ..
  6. Louik C, Lin A, Werler M, Hernandez diaz S, Mitchell A. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med. 2007;356:2675-83 pubmed
    ..They suggest that individual SSRIs may confer increased risks for some specific defects, but it should be recognized that the specific defects implicated are rare and the absolute risks are small. ..
  7. Vajda F, Hitchcock A, Graham J, Solinas C, O Brien T, Lander C, et al. Foetal malformations and seizure control: 52 months data of the Australian Pregnancy Registry. Eur J Neurol. 2006;13:645-54 pubmed
    ..The choice of AED for pregnant women with epilepsy requires assessment of balance of risks between teratogenicity and seizure control. ..
  8. Cunnington M, Ferber S, Quartey G. Effect of dose on the frequency of major birth defects following fetal exposure to lamotrigine monotherapy in an international observational study. Epilepsia. 2007;48:1207-10 pubmed
    ..999, 95% CI 0.996-1.001). There was also no effect of dose, up to 400 mg/day, on the frequency of MBDs. ..
  9. Alwan S, Reefhuis J, Rasmussen S, Olney R, Friedman J. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med. 2007;356:2684-92 pubmed
    ..Associations were observed between SSRI use and three types of birth defects, but the absolute risks were small, and these observations require confirmation by other studies. ..

More Information


  1. Jordan A, Parks L, Chen S, Higgins K, Fleischer A, Feldman S. Does the teratogenicity of isotretinoin outweigh its benefits?. J Dermatolog Treat. 2005;16:190-2 pubmed
  2. Pollack P, Shields K, Burnett D, Osborne M, Cunningham M, Stepanavage M. Pregnancy outcomes after maternal exposure to simvastatin and lovastatin. Birth Defects Res A Clin Mol Teratol. 2005;73:888-96 pubmed
    ..Drugs should be used during pregnancy only if the benefits outweigh the risks. Simvastatin and lovastatin remain contraindicated during pregnancy. ..
  3. Bar Oz B, Einarson T, Einarson A, Boskovic R, O Brien L, Malm H, et al. Paroxetine and congenital malformations: meta-Analysis and consideration of potential confounding factors. Clin Ther. 2007;29:918-926 pubmed publisher
    ..A significantly greater number of women were using paroxetine for anxiety or panic when compared with women using other SSRIs. ..
  4. Wogelius P, Nørgaard M, Gislum M, Pedersen L, Munk E, Mortensen P, et al. Maternal use of selective serotonin reuptake inhibitors and risk of congenital malformations. Epidemiology. 2006;17:701-4 pubmed
    ..It is unclear whether the effects were causal or due to factors related to the underlying disease. There was no evidence that the association was specific to particular malformations. ..
  5. Tatum W. Use of antiepileptic drugs in pregnancy. Expert Rev Neurother. 2006;6:1077-86 pubmed
    ..Although no class 1 outcome data are available, prepregnancy counseling to optimize patient-specific treatment is recommended for women of childbearing potential with epilepsy. ..
  6. Lipinski R, Song C, Sulik K, Everson J, Gipp J, Yan D, et al. Cleft lip and palate results from Hedgehog signaling antagonism in the mouse: Phenotypic characterization and clinical implications. Birth Defects Res A Clin Mol Teratol. 2010;88:232-40 pubmed publisher
    ..This work also illustrates the utility of fetal MRI-based analyses and establishes a novel mouse model for teratogen-induced CLP. ..
  7. Brar H, Einarson A. Effects and treatment of inflammatory bowel disease during pregnancy. Can Fam Physician. 2008;54:981-3 pubmed
    ..There are limited data on the use of infliximab during pregnancy, although no pattern of defects or complications has been reported to date. ..
  8. Hamlin H, Guillette L. Birth defects in wildlife: the role of environmental contaminants as inducers of reproductive and developmental dysfunction. Syst Biol Reprod Med. 2010;56:113-21 pubmed publisher
  9. Nolan L, Nolan J, Shofer F, Rodway N, Emmett E. Congenital anomalies, labor/delivery complications, maternal risk factors and their relationship with perfluorooctanoic acid (PFOA)-contaminated public drinking water. Reprod Toxicol. 2010;29:147-55 pubmed publisher
    ..Additional research is required to assess the observed associations between PFOA, anemia and dysfunctional labor. ..
  10. Singh G, Sinha N, Sinnollareddy M. Role of apoptosis in mediating salicylic acid-induced teratogenesis in vitro. Toxicol Mech Methods. 2009;19:161-8 pubmed publisher
    ..The data suggested that apoptosis might be involved in mediating teratogenesis of SAL in vitro. ..
  11. Tomson T, Battino D. Pregnancy and epilepsy: what should we tell our patients?. J Neurol. 2009;256:856-62 pubmed publisher
    ..Withdrawing or changing an AED should generally be avoided during pregnancy. Women with epilepsy on AED treatment should be encouraged to breast-feed. ..
  12. Whitehall J, Smith J. Valproate and babies. Aust N Z J Psychiatry. 2008;42:837 pubmed publisher
  13. Thompson J, Doi T, Power E, Balasubramanian I, Puri P, Bannigan J. Evidence against a direct role for oxidative stress in cadmium-induced axial malformation in the chick embryo. Toxicol Appl Pharmacol. 2010;243:390-8 pubmed publisher
    ..Furthermore, MDA levels 24 hours after treatment were identical in malformed and normal embryos exposed to Cd. Hence, we conclude that oxidative stress may not have a direct role in Cd teratogenesis. ..
  14. Liu J, Huang H, Zhang W, Li H. Cadmium-induced increase in uterine wet weight and its mechanism. Birth Defects Res B Dev Reprod Toxicol. 2010;89:43-9 pubmed publisher
    ..These results indicate that cadmium may induce an increase in uterine wet weight. However, this effect is not similar to that caused by 17beta-estradiol, suggesting it is not via Ca-ER interactions. ..
  15. Yüksel M, Sarikaya R, Bostanci N. Genotoxic evaluation of antiepileptic drugs by Drosophila somatic mutation and recombination test. Food Chem Toxicol. 2010;48:2682-7 pubmed publisher
    ..The results also show that all AED concentrations lower the survival rate of the flies...
  16. Paumgartten F, Solecki R, Buschmann J, Clark R, Grote K, Rauch M, et al. Harmonization of terminology in developmental toxicology: the quest for a more precise description and a harmonized classification of fetal observations. Reprod Toxicol. 2009;27:8-13 pubmed publisher
    ..The urgent need for additional research along this line as a prerequisite for a better risk assessment was emphasized by the participants. ..
  17. Cook D, Lee S, Gardner D, Pfister J, Welch K, Green B, et al. The alkaloid profiles of Lupinus sulphureus. J Agric Food Chem. 2009;57:1646-53 pubmed publisher
    ..In conclusion, taxonomic classification is not sufficient to determine risk, as chemical characterization of the alkaloids must also be performed. ..
  18. Pessah N, Kaufmann D, Yagen B, Hen N, Wlodarczyk B, Finnell R, et al. Comparative pharmacodynamic and pharmacokinetic analysis of two anticonvulsant halo derivatives of 2,2,3,3-tetramethylcyclopropanecarboxamide, an amide of a cyclic analog of valproic acid. Epilepsia. 2010;51:1944-53 pubmed publisher
    ..Based on their potent anticonvulsant activity and lack of teratogenicity, ?-F-TMCD and ?-Cl-TMCD have the potential for development as new antiepileptics and central nervous system (CNS) drugs. ..
  19. Schwarz E, Longo L, Zhao X, Stone R, Cunningham F, Good C. Provision of potentially teratogenic medications to female veterans of childbearing age. Med Care. 2010;48:834-42 pubmed publisher
    ..26; 95% CI, 1.18-1.34). Medications that may cause birth defects if used during pregnancy are dispensed frequently to female Veterans by VA pharmacies without documented receipt of contraceptive counseling or pregnancy testing. ..
  20. Diav Citrin O, Shechtman S, Schwartz V, Avgil Tsadok M, Finkel Pekarsky V, Wajnberg R, et al. Pregnancy outcome after in utero exposure to colchicine. Am J Obstet Gynecol. 2010;203:144.e1-6 pubmed publisher
    ..001) in the colchicine group. The present study suggests that colchicine does not appear to be a major human teratogen, and, probably, has no cytogenetic effect. ..
  21. Miller M, Ventura L, Strömland K. Thalidomide and misoprostol: Ophthalmologic manifestations and associations both expected and unexpected. Birth Defects Res A Clin Mol Teratol. 2009;85:667-76 pubmed publisher
    ..Autism spectrum disorder (ASD), an unexpected associated finding in a Swedish thalidomide study, is now also noted in Möbius studies, in patients both with and without exposure to misoprostol. ..
  22. Moretti M, Maxson A, Hanna F, Koren G. Evaluating the safety of St. John's Wort in human pregnancy. Reprod Toxicol. 2009;28:96-9 pubmed publisher
    ..Though further large scale studies are still needed, this first study on the effects of St. John's Wort in human pregnancy does provide some evidence of fetal safety. ..
  23. Ferrari A, Lascano C, Anguiano O, D Angelo A, Venturino A. Antioxidant responses to azinphos methyl and carbaryl during the embryonic development of the toad Rhinella (Bufo) arenarum Hensel. Aquat Toxicol. 2009;93:37-44 pubmed publisher
    ..The antioxidant enzymes are in turn revealing the balance between their protective capacity and the oxidative damage to the enzyme molecules, decreasing their activity. ..
  24. Ngo A, Taylor R, Roberts C. Paternal exposure to Agent Orange and spina bifida: a meta-analysis. Eur J Epidemiol. 2010;25:37-44 pubmed publisher
    ..86) and the cross sectional study (RR = 1.97, 95% CI: 1.31-2.96), but not for the three cohort studies (RR: 2.11; 95% CI: 0.78-5.73). Paternal exposure to AO appears to be associated with a statistically increased risk of spina bifida. ..
  25. van Gelder M, van Rooij I, Miller R, Zielhuis G, de Jong van den Berg L, Roeleveld N. Teratogenic mechanisms of medical drugs. Hum Reprod Update. 2010;16:378-94 pubmed publisher
  26. Castelain M. [Side effects, complications and contraindications of patch-tests]. Ann Dermatol Venereol. 2009;136:645-9 pubmed publisher
    ..The associated contraindications are dependent on the patient's status (immunodepression, pregnancy, ongoing eczema) and on the allergen in question (unknown, irritant, sensitizing). ..
  27. Schneider T, Bizarro L, Asherson P, Stolerman I. Gestational exposure to nicotine in drinking water: teratogenic effects and methodological issues. Behav Pharmacol. 2010;21:206-16 pubmed
    ..There were marked developmental and behavioural deficits induced in the offspring of nicotine-exposed female rats. ..
  28. Van Abel K, Nelson M, Collar R, Lesperance M. Development of canal cholesteatoma in a patient with prenatal isotretinoin exposure. Int J Pediatr Otorhinolaryngol. 2010;74:1082-4 pubmed publisher
    ..Close monitoring for development of canal cholesteatoma is necessary. ..
  29. Tung E, Winn L. Epigenetic modifications in valproic acid-induced teratogenesis. Toxicol Appl Pharmacol. 2010;248:201-9 pubmed publisher
    ..These results support the possibility that epigenetic modifications caused by VPA during early mouse organogenesis results in congenital malformations. ..
  30. Augspurger T, Tillitt D, Bursian S, Fitzgerald S, Hinton D, Di Giulio R. Embryo toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the wood duck (Aix sponsa). Arch Environ Contam Toxicol. 2008;55:659-69 pubmed publisher
  31. Pentsuk N, van der Laan J. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86:328-44 pubmed publisher
  32. Carey J. "Where observation is concerned, chance favors only the prepared mind". Obstet Gynecol. 2008;111:479-80 pubmed publisher
  33. Weber Schoendorfer C, Hannemann D, Meister R, Elefant E, Cuppers Maarschalkerweerd B, Arnon J, et al. The safety of calcium channel blockers during pregnancy: a prospective, multicenter, observational study. Reprod Toxicol. 2008;26:24-30 pubmed publisher
    ..6.5%). These adverse effects are more likely due to the underlying disease than to the medication. This study suggests that calcium channel blockers during the first trimester of pregnancy do not represent a major teratogenic risk. ..
  34. Thilagam H, Gopalakrishnan S, Vijayavel K, Raja P. Effluent toxicity test using developmental stages of the marine polychaete Hydroides elegans. Arch Environ Contam Toxicol. 2008;54:674-83 pubmed publisher
    ..elegans are suitable for the assessment of effects produced by low levels of pollutants due to their high sensitivity to various contaminants relative to other marine species and also due to the relative simplicity of the bioassay. ..
  35. Jentink J, Loane M, Dolk H, Barisic I, Garne E, Morris J, et al. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med. 2010;362:2185-93 pubmed publisher
    ..The use of valproic acid monotherapy in the first trimester was associated with significantly increased risks of several congenital malformations, as compared with no use of antiepileptic drugs or with use of other antiepileptic drugs. ..
  36. Nordeng H, Ystrøm E, Einarson A. Perception of risk regarding the use of medications and other exposures during pregnancy. Eur J Clin Pharmacol. 2010;66:207-14 pubmed publisher
    ..Therefore, it is important for health care providers to use evidence-based information, to reduce unnecessary anxiety, and to ensure safe and appropriate treatment during pregnancy. ..
  37. Roy M, Leclerc D, Wu Q, Gupta S, Kruger W, Rozen R. Valproic acid increases expression of methylenetetrahydrofolate reductase (MTHFR) and induces lower teratogenicity in MTHFR deficiency. J Cell Biochem. 2008;105:467-76 pubmed publisher
    ..These results underscore the importance of folate interconversion in VPA-induced teratogenicity, since VPA increases MTHFR expression and has lower teratogenic potential in MTHFR deficiency. ..
  38. Eadie M. Antiepileptic drugs as human teratogens. Expert Opin Drug Saf. 2008;7:195-209 pubmed
  39. Regitz Zagrosek V, Schubert C, Kruger S. [Gender differences in psychopharmacology]. Internist (Berl). 2008;49:1516-9, 1521-3 pubmed publisher
    ..The risk that a mother with a psychiatric disorder could relapse if the drug is discontinued has to be weighed against the risk of the child being born with an anomaly or developing prenatal complications. ..
  40. Czeizel A, Puho E, Acs N, Banhidy F. Delineation of a multiple congenital abnormality syndrome in the offspring of pregnant women affected with high fever-related disorders: a population-based study. Congenit Anom (Kyoto). 2008;48:158-66 pubmed publisher
    ..0%) among 181 MCA babies born to mothers with high fever-related diseases. In the total dataset of 1349 MCA, 2.8% of cases can be associated with high fever. ..
  41. Walker S, Permezel M, Berkovic S. The management of epilepsy in pregnancy. BJOG. 2009;116:758-67 pubmed publisher
    ..During pregnancy, important considerations include; therapeutic drug monitoring, surveillance for obstetric complications and vigilance for seizures during the intrapartum and postpartum period. ..
  42. Xu C, Liu W, Chen Z, Wang Y, Xiong Z, Ji Y. Effect of prenatal tetrandrine administration on transforming growth factor-beta1 level in the lung of nitrofen-induced congenital diaphragmatic hernia rat model. J Pediatr Surg. 2009;44:1611-20 pubmed publisher
    ..It is a likely new approach to treat CDH and its coexistent lung hypoplasia by maternal Tet administration. ..
  43. Vajda F. Treatment options for pregnant women with epilepsy. Expert Opin Pharmacother. 2008;9:1859-68 pubmed
    ..Traditional prescribing patterns appear to influence the options for treatment of women with epilepsy in pregnancy, which is then adjusted according to the variability of response. ..
  44. Petersen E, Mitchell A, Carey J, Werler M, Louik C, Rasmussen S. Maternal exposure to statins and risk for birth defects: a case-series approach. Am J Med Genet A. 2008;146A:2701-5 pubmed publisher
  45. Pérez Pastén R, Martínez Galero E, Chamorro Cevallos G. Quercetin and naringenin reduce abnormal development of mouse embryos produced by hydroxyurea. J Pharm Pharmacol. 2010;62:1003-9 pubmed publisher
    ..These results indicate that quercetin and naringenin have not only a minor toxic effect on development, but also a protective effect against hydroxyurea-induced embryonic damage. ..
  46. Kransler K, McGarrigle B, Russell R, Olson J. Effects of Helicobacter infection on developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Holtzman rats. Lab Anim (NY). 2008;37:171-5 pubmed publisher
    ..All rats were affected by TCDD, and Helicobacter infection seemed to have little influence on rats' susceptibility to the compound. ..
  47. Schoner K, Steinhard J, Figiel J, Rehder H. Severe facial clefts in acrofacial dysostosis: a consequence of prenatal exposure to mycophenolate mofetil?. Obstet Gynecol. 2008;111:483-6 pubmed publisher
    ..Mycophenolate mofetil may have contributed to or even caused acrofacial dysostosis phenotype and extensive clefting. ..
  48. Gidai J, Acs N, Banhidy F, Czeizel A. Congenital abnormalities in children of 43 pregnant women who attempted suicide with large doses of nitrazepam. Pharmacoepidemiol Drug Saf. 2010;19:175-82 pubmed publisher
    ..The self-poisoning pregnant women model is feasible for the evaluation of teratogenic effect of drugs. ..
  49. Cardonick E, Usmani A, Ghaffar S. Perinatal outcomes of a pregnancy complicated by cancer, including neonatal follow-up after in utero exposure to chemotherapy: results of an international registry. Am J Clin Oncol. 2010;33:221-8 pubmed publisher
    ..There was a statistical significant difference in the birth weight between groups, which may not be clinically significant. ..
  50. Shi H, Qian L, Guo S, Zhang X, Liu J, Cao Q. Teratogenic effects of tetrabromobisphenol A on Xenopus tropicalis embryos. Comp Biochem Physiol C Toxicol Pharmacol. 2010;152:62-8 pubmed publisher
    ..These results indicate that TBBPA at relatively high concentration has teratogenic effects on X. tropicalis embryos. The results also suggest that thyroid hormone signaling might be involved in TBBPA induced-teratogenicity. ..
  51. Peng H, Wang Y, Wen C, Wang W, Cheng C, Chen Y. Nephrotoxicity assessments of acetaminophen during zebrafish embryogenesis. Comp Biochem Physiol C Toxicol Pharmacol. 2010;151:480-6 pubmed publisher
    ..In conclusion, AAP-induced defects on glomerulus, pronephric tube and pronephric duct could be easily and dynamically observed in vivo during kidney development in this present model. ..
  52. Gürbüzer N, Yurtcu M, Findik S, Avunduk M, Gunel E. Investigation of histopathologic changes in the ureter walls in experimental congenital obstructive uropathy. J Pediatr Surg. 2008;43:1524-7 pubmed publisher
    ..The diameter of the ureter lumen and wall thickness of ureter (tunica muscularis of ureter and uroepithelium) were increased following obstructive uropathy after the birth. ..
  53. Afshar M, Moallem S, Houshang Mohammadpour A, Shiravi A, Majid Jalalian S, Jafar Golalipour M. Teratogenic effects of carbamazepine on embryonic eye development in pregnant mice. Cutan Ocul Toxicol. 2010;29:10-5 pubmed publisher
    ..The implication of these results needs to be considered when carbamazepine is administered during human pregnancy. ..