title: Reflections on the etiology of structural birth defects: Established teratogens and risk factors.
abstract: BACKGROUND
  Various experts in clinical teratology have proposed what they consider to be well-established teratogens. With the recent growth in the number of resources and investigations, there has been a notable proliferation of proposed risk factors as potential causes of human congenital structural defects. The purpose of this Commentary is to provide a concise summary of the current state of knowledge regarding known causes and environmental risk factors of structural defects.
  
  
  METHODS
  We performed a comprehensive search of PubMed for papers in English and in humans only, 2010 to 2014, that included birth defects, risk factors, and teratogens as key terms.
  
  
  RESULTS
  Our search led to over 9000 papers dealing with these categories. From this, we were able to construct a timetable documenting the recognition of human teratogens and list several proposed environmental risk factors. Three relevant current trends were noticed: An increase of prescription and nonprescription medication use by women during pregnancy; the rise in obesity and its association with structural defects; and a growing body of work regarding outcomes associated with assisted reproductive technology.
  
  
  CONCLUSIONS
  There are numerous risk factors, some modifiable, that have been proposed in recent years. These factors (associations) are only at the preliminary level in the causal chain and require replication. There is a need for more work on protective factors. The phenotypic characterization of cases with congenital defects has improved remarkably in recent years. However, there remains considerable concern with the precise characterization of exposures and the documentation of timing during embryologic development.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Feldkamp
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Lorenzo D
authors.initials: LD
authors.lastname: Botto
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: John C
authors.initials: JC
authors.lastname: Carey
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000013:Congenital Abnormalities / Q000209:etiology*; D005260:Female; D006801:Humans; D011247:Pregnancy; D012307:Risk Factors; D013723:Teratogens / Q000494:pharmacology*
chemical_list: D013723:Teratogens
keywords: birth defects; congenital structural defects; etiology; malformations; risk factors; teratogens