**2.4 Epidemiology of oesophageal atresia**

The incidence of OA, with or without TOF, is reported to be 1:3500 live-born infants. This, however, varies geographically [23] from 1 in 2440 births in Finland to 1 in 4500 births in the United States and Australia. In a European study, 62% of infants with OA-TOF were male, whereas a California database found considerable variations in the male-to-female ratios between types of OA-TOF defects [23]. Mothers of white ethnicity have a higher (>60%) prevalence of OA-TOF than nonwhite populations do [23]. First pregnancy and increasing maternal age have been found to be associated with an increased risk OA-TOF [23]. The risk is reported to be twofold for women 35–40 years old and threefold for those older than this age [23]. Offspring of in vitro fertilization patients also have a significantly increased risk of developing OA (OR 3.65:CI 2/53–5/26) [23].

#### **2.5 Anatomic (pathologic) classification of oesophageal atresia**

Various systems of classifications have been used to classify OA. The two most frequently used ones are shown in **Table 1** [24].

### **2.6 Associated anomalies**

About 50–70% of patients with oesophageal atresia have associated congenital anomalies [23]. Cases without tracheo-oesophageal fistula tend to be most commonly associated with other anomalies, while those with the H-type are less commonly associated with other anomalies. Associated anomalies may negatively affect patient management and overall outcome of patients.


**53**

**Table 2.**

*Oesophageal Atresia: Drowning a Child in His/Her Own Saliva*

anomalies or single gene mutations (**Tables 2** and **3**) [23, 26].

About 50% of patients with associated anomalies have recognizable syndromes, sequences, and associations [23]. VACTERL (vertebral, anorectal malformation, cardiac, tracheo-oesophageal, renal, limb) association is found in 20% of cases [25]. These syndromes, sequences, and associations usually result from chromosomal

The most common CVS anomalies are ventricular septal defect (VSD) and atrial septal defect (ASD). Other CVS defects include tetralogy of Fallot, patent ductus arteriosus (PDA), and coarctation of the aorta. A few patients tend to have the descending thoracic aorta on the right side. Renal agenesis or hypoplasia, undescended testis, cystic renal disease, hydronephrosis, vesicoureteric reflux (VUR) and ureteric duplication are some of the GUT anomalies associated with oesophageal atresia. Other GUT anomalies include pelvi-ureteric junction (PUJ) obstruction, vesicoureteric junction (VUJ) obstruction, urachal anomalies, ambiguous genitalia, bladder exstrophy and cloacal exstrophy. The GIT anomalies found in oesophageal atresia include anorectal malformation (ARM), duodenal atresia, intestinal malrotation, ileal atresia, annular pancreas and pyloric stenosis. Vertebral and radial abnormalities are the usual MSS defects associated with oesophageal atresia. The CNS defects found in oesophageal atresia include neural tube defects,

hydrocephalus, holoprosencephaly and anophthalmia or microphthalmia.

The discontinuation of the oesophageal lumen prevents swallowed amniotic fluid by the foetus from reaching the stomach and hence the intestine. In view of this, the physiological control of amniotic fluid volume by the foetus, through swallowing and absorption, is impaired, leading to polyhydramnios. This would in turn lead to premature rupture of membrane, umbilical cord prolapse and premature delivery.

**2.7 Pathophysiology of oesophageal atresia**

*Chromosomal abnormalities associated with oesophageal atresia.*

Patients with oesophageal atresia have trisomies 18 and 21 in about 7% of patients. In trisomy 21 (Down syndrome), the possibility of associated duodenal atresia, Hirschsprung's disease and congenital heart disease should be considered. In patients with clinically suspected trisomy 18, surgery should be postponed and chromosomal analysis done immediately since prognosis for trisomy 18 is very poor. The common associated anomalies in non-syndromic oesophageal atresia include the cardiovascular system (CVS), genitourinary tract (GUT), gastrointestinal tract (GIT), musculoskeletal system (MSS), and central nervous system (CNS) (**Table 4**). Cardiovascular anomalies tend to occur most frequently (**Table 4**) [23, 25, 27]. This is followed by the GUT, GIT, MSS, and CNS (neurologic anomalies). A review of cases seen at our centre in Accra Korle-Bu, however, showed overall incidence of associated anomalies of 32.5%, with GIT system being the most commonly affected, followed by

*DOI: http://dx.doi.org/10.5772/intechopen.84525*

the CVS [9].

#### **Table 1.**

*Types of oesophageal atresia—anatomic (pathologic) classification of oesophageal atresia.*

*Pediatric Surgery, Flowcharts and Clinical Algorithms*

**2.4 Epidemiology of oesophageal atresia**

risk of developing OA (OR 3.65:CI 2/53–5/26) [23].

frequently used ones are shown in **Table 1** [24].

patient management and overall outcome of patients.

**2.6 Associated anomalies**

**2.5 Anatomic (pathologic) classification of oesophageal atresia**

and diethylstilbestrol are also found to be associated with OA.

Aetiologically, various genetic defects have been found to be associated with oesophageal atresia. Important genes related to the pathogenesis of OA, and mostly involved in developmental pathways, include vitamin A effectors, retinoic acid receptors a and b (Rara and Rarb), sonic hedgehog pathway effectors (Shh, Gli2, Gli3 and Foxf1) and other homeobox containing transcription factors (Hoxc4, Ttf-1 and Pcsk5) [23]. Various environmental teratogens have also been implicated in the pathogenesis of OA-TOF [23]. Infants born to mothers with prolonged exposure to contraceptive pills (exposure to progesterone and oestrogen) during pregnancy have high risk. Oesophageal atresia has also been reported in some infants of hyperthyroid and uncontrolled diabetic mothers. Intrauterine exposure to thalidomide

The incidence of OA, with or without TOF, is reported to be 1:3500 live-born infants. This, however, varies geographically [23] from 1 in 2440 births in Finland to 1 in 4500 births in the United States and Australia. In a European study, 62% of infants with OA-TOF were male, whereas a California database found considerable variations in the male-to-female ratios between types of OA-TOF defects [23]. Mothers of white ethnicity have a higher (>60%) prevalence of OA-TOF than nonwhite populations do [23]. First pregnancy and increasing maternal age have been found to be associated with an increased risk OA-TOF [23]. The risk is reported to be twofold for women 35–40 years old and threefold for those older than this age [23]. Offspring of in vitro fertilization patients also have a significantly increased

Various systems of classifications have been used to classify OA. The two most

About 50–70% of patients with oesophageal atresia have associated congenital anomalies [23]. Cases without tracheo-oesophageal fistula tend to be most commonly associated with other anomalies, while those with the H-type are less commonly associated with other anomalies. Associated anomalies may negatively affect

**52**

**Table 1.**

*Types of oesophageal atresia—anatomic (pathologic) classification of oesophageal atresia.*

About 50% of patients with associated anomalies have recognizable syndromes, sequences, and associations [23]. VACTERL (vertebral, anorectal malformation, cardiac, tracheo-oesophageal, renal, limb) association is found in 20% of cases [25]. These syndromes, sequences, and associations usually result from chromosomal anomalies or single gene mutations (**Tables 2** and **3**) [23, 26].

Patients with oesophageal atresia have trisomies 18 and 21 in about 7% of patients. In trisomy 21 (Down syndrome), the possibility of associated duodenal atresia, Hirschsprung's disease and congenital heart disease should be considered. In patients with clinically suspected trisomy 18, surgery should be postponed and chromosomal analysis done immediately since prognosis for trisomy 18 is very poor.

The common associated anomalies in non-syndromic oesophageal atresia include the cardiovascular system (CVS), genitourinary tract (GUT), gastrointestinal tract (GIT), musculoskeletal system (MSS), and central nervous system (CNS) (**Table 4**). Cardiovascular anomalies tend to occur most frequently (**Table 4**) [23, 25, 27]. This is followed by the GUT, GIT, MSS, and CNS (neurologic anomalies). A review of cases seen at our centre in Accra Korle-Bu, however, showed overall incidence of associated anomalies of 32.5%, with GIT system being the most commonly affected, followed by the CVS [9].

The most common CVS anomalies are ventricular septal defect (VSD) and atrial septal defect (ASD). Other CVS defects include tetralogy of Fallot, patent ductus arteriosus (PDA), and coarctation of the aorta. A few patients tend to have the descending thoracic aorta on the right side. Renal agenesis or hypoplasia, undescended testis, cystic renal disease, hydronephrosis, vesicoureteric reflux (VUR) and ureteric duplication are some of the GUT anomalies associated with oesophageal atresia. Other GUT anomalies include pelvi-ureteric junction (PUJ) obstruction, vesicoureteric junction (VUJ) obstruction, urachal anomalies, ambiguous genitalia, bladder exstrophy and cloacal exstrophy. The GIT anomalies found in oesophageal atresia include anorectal malformation (ARM), duodenal atresia, intestinal malrotation, ileal atresia, annular pancreas and pyloric stenosis. Vertebral and radial abnormalities are the usual MSS defects associated with oesophageal atresia. The CNS defects found in oesophageal atresia include neural tube defects, hydrocephalus, holoprosencephaly and anophthalmia or microphthalmia.
