**5. Summary**

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

age, and also between a young father and mother of advanced age.

prevalence of major CA in males is 3.9% compared to 2.8% in females [17].

**4.1 Calculation of carrier frequency and recurrence risk in a population**

mating is random and there are no new mutations or natural selections.

*4.1.1 Calculation of carrier frequency*

100%); 2PQ =carrier frequency; P<sup>2</sup>

*4.1.2 Calculation of recurrence risk of CF*

having an affected child?

The Hardy-Weinberg equilibrium is utilized to predict carrier frequency in a given population and to calculate recurrence risk. The calculation assumes that the

Example: Normal gene frequency=P; Abnormal gene frequency =Q; P+Q =1 (i.e.

Let us take the example of cystic fibrosis (CF), an autosomal recessive disease.

1/2500; therefore Q= 1/50. We know that P+Q=1. So P=1-Q or 1-1/50 = 49/50 ~ 1.

Example: a pregnant woman has a sister with CF. What are the chances of her

The disease frequency of the morbidity is 1 in 2500 Caucasian births. I.e., Q2

Therefore 2PQ (carrier frequency) = 2 \* 1 \* 1/50 = 1/25.

= normal, non-carrier frequency; Q2

= affected

=

as well as hips and feet deformities [13]. Advanced paternal age is associated with an increased incidence of de novo DNA mutations and chromosomal aberrations in the sperm, which may lead to miscarriage or genotypical and/or phenotypical anomalies in the fetus [14]. Like advanced maternal age, trisomy 21 is documented to be associated with advanced paternal age as well [15]. Other disorders reported to occur more commonly with advanced paternal age are achondroplasia, osteogenesis imperfecta, and some syndromes such as Apert, Waardenburg, Marfan, and Treacher Collins.

Green et al. have reported that the risks for cleft palate, diaphragmatic hernia, right ventricular outflow tract obstruction, pulmonary valve stenosis, anomalous pulmonary venous return, cataract, aortic coarctation, encephalocele, esophageal atresia, and multiple complex defects in the offsprings are enhanced with each unit year increase in the paternal age [14]. It is noteworthy that the effects of paternal age might vary in tandem with maternal age. While young maternal and paternal age are identified as independent risk factors for gastroschisis, young paternal age can become a risk factor for gastroschisis again if the mother's age exceeds 35 years. Omphalocele, spina bifida, orofacial clefts, and septal heart defects display associations with parental mating, which involves advanced paternal and young maternal

Some diseases exhibit gender preferences [16, 17]. The diseases known to occur more commonly in males are pyloric stenosis, Hirschsprung's disease, imperforate anus, club foot, unilateral multicystic dysplastic kidney; cleft lip and palate, Poland sequence, ventricular septal defect, transposition of great vessels, aortic coarctation, hypoplastic left heart syndrome, subdiaphragmatic total anomalous pulmonary venous return, and pulmonic stenosis and atresia. Disorders identified to be more common in females are choanal atresia, choledochal cyst, congenital hip dysplasia, ureterocele, Trisomy 18, atrial septal defect, patent ductus arteriosus, anencephaly, meningomyelocele and congenital hypothyroidism. In a recent study of 12,795 cases with CA, male fetuses were found to be more susceptible to birth defects than females, however, with significant heterogeneity in the subtypes [16]. Sex organ anomalies are reported to be 8.5 times more common, and GIT defects 55%, whereas urinary tract anomalies 62% more prevalent in males than in females. Overall, the

**10**

frequency.

Congenital anomalies are a heterogeneous group of disorders of abnormal morphogenesis, which present at birth and carry widely variable implications for morbidity and mortality. The basics of incidence, pathogenesis, and risk assessments of CA are discussed in this section.
