Application of Pharmacogenomic Strategies to the Study of Drug-induced Birth Defects

Abstract

Approximately 3% of all infants are born with one or more major birth defects, resulting in >150,000 affected babies each year in the US alone. At present, birth defects account for more than 21% of all infant deaths, making them the leading cause of infant mortality. Although the etiology and determinants of individual susceptibility are largely unknown for most congenital malformations, pharmacogenomic analyses offer promise for the future.

Maternal–fetal and neonatal pharmacogenomics: a review of current literature

“…As a result, many expectant mothers and their medical caretakers need to weigh the balance between risk and benefit of antepartum drug exposure. 12 …”

“…10,11 Although the risk of exposure to ‘high-risk’ teratogens, such as thalidomide or isotretinoin, is low, it is currently unclear what predisposes certain fetuses to the harmful effects of the more commonly used ‘moderate-risk’ medications, such as anticonvulsants and anticoagulants (Table 2). 12 In addition, 7% of children in the United States have developmental disorders by age 1, 12–14% by the time they enter school and 17% before age 18; the role that in utero drug exposure may have in developmental disorders continues to be studied. 13 …”

“…12 Thus, medications administered with therapeutic intent have the potential to disrupt normal cellular function through competition with endogenous substrates and ligands.…”

Pharmacogenetics and Perinatal Clinical Pharmacology: Tool or Toy?

“…Theoretically, there is the potential of age-specific concordances between genotype-phenotype in perinatal life that can only be unveil following focused evaluation in this population [2,11,12]. This includes the developmental context in which specific genes with known polymorphisms are active: the genotype-phenotype correlation may no longer apply beyond infancy.…”