**4. Risk assessment of congenital anomalies**

The assessment of risks for CA may not always be possible due to the lack of referable evidence and information. The known recurrence risks of some of the heritable disorders are presented in **Table 1**. Some of the risk factors for CA are well documented, such as parental age, subjects' gender, geographical location and exposure to drugs or toxins etc. Advanced maternal age is extensively reported to be associated with aneuploidies, such as trisomy 21, 13, and 18 and Klinefelter syndrome. Advanced maternal age has also been associated with non-chromosomal genitourinary anomalies,


#### **Table 1.**

*Recurrence risk of certain malformations. (adapted from Jones KL, Smiths recognizable patterns of human malformations, 5th edition, WB Saunders, Philadelphia, 1997; and Neonatology Review, 2nd edition, D. Brodsky & C. Martin, Hanley and Belfus Inc.2003.*

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

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 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**

The Hardy-Weinberg equilibrium is utilized to predict carrier frequency in a given population and to calculate recurrence risk. The calculation assumes that the mating is random and there are no new mutations or natural selections.

#### *4.1.1 Calculation of carrier frequency*

Example: Normal gene frequency=P; Abnormal gene frequency =Q; P+Q =1 (i.e. 100%); 2PQ =carrier frequency; P<sup>2</sup> = normal, non-carrier frequency; Q2 = affected frequency.

Let us take the example of cystic fibrosis (CF), an autosomal recessive disease. The disease frequency of the morbidity is 1 in 2500 Caucasian births. I.e., Q2 = 1/2500; therefore Q= 1/50. We know that P+Q=1. So P=1-Q or 1-1/50 = 49/50 ~ 1. Therefore 2PQ (carrier frequency) = 2 \* 1 \* 1/50 = 1/25.

#### *4.1.2 Calculation of recurrence risk of CF*

Example: a pregnant woman has a sister with CF. What are the chances of her having an affected child?

**11**

**Author details**

Rita Prasad Verma

Nassau University Medical Center, East Meadow, NY, USA

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: rverma2@numc.edu

provided the original work is properly cited.

*Introductory Chapter: Epidemiology, Evaluation and Risk Assessment of Congenital Anomalies*

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 assess-

The Father's risk of being a carrier is 1/25, while the mother's chances of being a carrier are 2/3 as both of her parents are carriers. The chance of the offspring getting the gene from each parent is ¼. Therefore the chances of the child being

*DOI: http://dx.doi.org/10.5772/intechopen.97181*

affected by CF are 1/25X2/3X1/4=1/150.

ments of CA are discussed in this section.

**5. Summary**

*Introductory Chapter: Epidemiology, Evaluation and Risk Assessment of Congenital Anomalies DOI: http://dx.doi.org/10.5772/intechopen.97181*

The Father's risk of being a carrier is 1/25, while the mother's chances of being a carrier are 2/3 as both of her parents are carriers. The chance of the offspring getting the gene from each parent is ¼. Therefore the chances of the child being affected by CF are 1/25X2/3X1/4=1/150.
