**2.1 Drugs**

*Congenital Anomalies in Newborn Infants - Clinical and Etiopathological Perspectives*

Congenital anomalies are health problems that are difficult to rehabilitate. They generate high treatment costs and might bring on huge financial and moral burdens to the family and society. According to the congenital anomalies survey conducted by the World Health Organization (WHO) in 193 countries in 2010, 270,000 of the 3.1 million newborn deaths were caused by congenital anomalies [6]. In the United States, 2–3% cases of the 3–5% of children born with birth defects are attributed to environmental or iatrogenic teratogen exposure during the intrauterine (IU) life

Teratogens may cause significant congenital anomalies if encountered during the organogenesis period of 3–8 weeks of fetal life, which is the stage of tissue and organ formations (**Figure 1**). Minor morphological and functional disorders may occur with exposure during the fetal period of the first 2 weeks [8]. Multiple factors come into play for the teratogens to impart their effects. These are the genetic specifications of the conceptus, the dose and duration of exposure, and the mechanism of action of the offending agent. Teratogens effectuate primarily by disrupting cell-specific biochemical metabolism and by compromising blood circulation which lead to cell death. They can destroy and deplete essential nutrients, block enzyme activities, disrupt mitosis, interfere with nucleic acid functions, and derange membrane functions, osmolar balance, and energy production [9, 10]. Genetic differences in response to teratogens have been documented and may be due to the presence of genetic polymorphisms in the activities of enzymes involved in the excretion of toxic substances [11]. Animal studies have shown differences in the susceptibility to teratogen-induced damage within the same as well as between different species. Fetal hydantoin syndrome is detected in 5% of embryos exposed to phenytoin (PTN), and about 30% of them show some congenital anomalies, while more than half display no teratogenic effects [12]. Aspirin, corticosteroids,

[7]. Most of the teratogen-induced anomalies are preventable.

**2. Teratogenic agents**

*Sensitivity to teratogens during pregnancy.*

**Figure 1.**

**16**

Drugs can directly affect the product of conception and cause malformation and/or embryo-fetal demise. They can impair the fetal development by compromising the transplacental transfer of nutrients and oxygen from the mother. They may diminish fetal blood supply and initiate premature myometrial contractions resulting in premature birth [14]. Drugs can play roles in the intrauterine development of gene-encoding proteins, thereby altering transcription regulation signals which adversely affect embryogenesis [15]. Drugs can exert their effects at different stages of cell development, namely, replication, proliferation, gene expression, signal transduction, programmed cell death, and cell migration (**Table 1**) [16, 17].
