**3.2.1 Maternal health and medical disease**

Certain chronic illnesses in the mother (table 6), such as diabetes, and other viral infections, such as the flu, may contribute to heart defects.


key risk is that the babies are genetically oriented towards some level of atypical cardiovascular formation and/or development, together with the exposure to other causative factors. Different stages of cardiac development possess various degrees of vulnerability to environmental factors. Some clues to multifactorial inheritances are a reason for CHD, including a lack of consistent CHD people in the pedigree of the family, and an

Various teratogenic agents have been implicated as the etiologic agents of CHD. For example, women who have insulin-dependent diabetes mellitus, and those who take certain medications, such as acne and epilepsy medication, have a higher risk for having babies with CHD. Women with drug or alcohol abuse also have predisposing risks. The basic biological principle mechanism of teratogens action that cause CHD include susceptible stage of organogenesis development, genetic differences in susceptibility, dose response relationships, and specific actions of the teratogenic agent. The highest degree of embryonic and fetal sensitivity or susceptibility to adverse effects of exposure to teratogens occurs during the first trimester, especially during the 2nd to 8th week of embryonic life. Dose response relationship implies that for each teratogen there is a dose threshold, theoretic dose

Certain chronic illnesses in the mother (table 6), such as diabetes, and other viral infections,

 **Maternal diabetes mellitus;** The study by Correa et al. found odds ratios for pregestational diabetes mellitus (PGDM) and all cardiac defects was 4.64 (2.87-7.51), while gestational diabetes mellitus (GDM) was associated with cardiac defects found 1.59 (1.27-1.99) (Correa et al., 2008). This excess risk is related to the level of maternal hyperglycemia during the embryonic period. The overall risk of one or more major anomalies is 6 to 7 percent, which is double the risk in the general obstetric population (Wyatt et al., 2005). Congenital heart defects increased in diabetic pregnancy include heterotaxy, TOF, TGA, septal defects, anomalous pulmonary venous return, and various defects causing left or right outflow obstruction (Lisowski et al., 2010; Corrigan et al., 2003; Wren et al., 2003). The possible mechanism is that embryonic hyperglycemia may cause disturbances in metabolism of arachidonic acid, inositol and promote excessive formation of oxygen free radicals which causes mitochondrial damage, and

 **Maternal phenylketonuria;** One of the most common teratogen of pregnancy complications, when these pregnancies are untreated, 90% of the offspring suffer microcephaly, mental retardation and increased risk of heart defects through increased blood levels of phenylalanine and phenyl pyruvic acid (Rouse & Azen, 2004). Frequencies of congenital abnormalities increased with increasing maternal phenylalanine levels. The MPKUCS has demonstrated an increased rate of CHD (7.5%), the most frequent cardiac defects are TOF, Coarc, PDA, HLH and VSD (Levy et al., 2001). Diet control before conception and during pregnancy reduces the risk of CHD

occasional abnormality with no recognizable pattern in the pedigree of the family.

**3.2 Maternal factors** 

below which no adverse effects can be observed.

**3.2.1 Maternal health and medical disease** 

such as the flu, may contribute to heart defects.

activation of apoptotic pathways.

(Matalon et al., 2003; Michals-Matalon et al., 2002).


#### **3.2.2 Maternal drug and medical use**

Consumption of many drugs, such as thalidomide and isotretinoin, during early gestationcan interfere with the normal cardiogenesis of the fetus. This list of definite and potential human cardiac teratogens was showed in table 6.

#### **3.2.3 Maternal drugs abuse**

Some studies suggest that drinking alcohol or using cocaine, especially during the pregnancy, can increase the risk of congenital heart defects (table 6).

(Ref: 1Lisowski et al., 2010; 2Corrigan et al., 2009; 3Wren et al., 2003; 4Rouse & Azen, 2004; 5Buyon et al., 2009; 6Clancy & Buyon, 2004; 7Row, 1973; 8De Santis et al., 2006; 9Webster, 1998; 10Botto et al., 2001; 11Carmichael & Shaw, 2000; 12Adam et al., 1989; 13Cedergren & Kallen, 2003; 14Mills et al., 2010; 15Oddy et al., 2009; 16Gilboa et al., 2010; 17Cohen et al., 1994; 18Jacobson et al., 1992; 19Rothman et al., 1995; 20Botto et al., 2001; 21Lammer et al., 1985; 22Willhite et al., 1986; 23Rischbieth, 1979; 24O'Brien & Gilmour-White, 1993; 25Sonoda et al., 1993; 26Winter et al., 1987; 27Hou, 2004; 28Smithells & Newman, 1992; 29Ericson & Kallen, 2001; 30Czeizel et al., 2001; 31Newman & Correy, 1983; 32Crider et al., 2009; 33Cooper et al., 2006; 34Kallen & Otterblad Olausson, 2006; 35Bar-Oz et al., 2007; 36Berard et al., 2007; 37Pejtsil et al., 1992; 38Carmichael et al., 2003; 39Burd et al., 2007; 40Loser et al., 1992; 41Alverson et al., 2011; 42Malik et al., 1999; 43Kallen, 1999; 44Linn et al., 1982; 45Kuehl & Loffredo, 2002; 46Lipshultz et al., 1991; 47Martin & Khoury, 1992; 48Tikkanen & Heinonen, 1991; 49Shaw et al., 2003; 50Tikkanen et al., 1992; 51Gilboa et al., 2005; 52Dadvand et al., 2011)

Table 6. Risk factors that are known or believed to be associated with the congenital heart defects.

