Duodenal atresia [9]

Duodenal atresia has an incidence of 1 in 5000–10 000 live births. The diagnosis is suspected on ultrasound when polyhydramnios and a double‐bubble appearance (due to a dilated stomach and proximal duodenum) are present. Duodenal atresia results from failure of recanalization of the duodenum after the seventh week of gestation, possibly due to an ischaemic event; occasionally, genetic factors may also play a role. Although sometimes seen earlier in gestation, the diagnosis is usually made after 24 weeks. Approximately 50% of cases of duodenal atresia have associated structural anomalies. Almost 30% are associated with Down’s syndrome and other anomalies are usually related to the VACTERL group (Vertebral, Anorectal, Cardiac, TracheoEsohageal, Renal and Limb). If the diagnosis is suspected on antenatal ultrasound, karyotyping must be offered because of the high risk of Down’s syndrome. Because of the significant risk of polyhydramnios (50%), regular scans are required and amnioreduction may be necessary if the amniotic fluid index increases substantially or if the patient is symptomatic. Preterm labour occurs in approximately 40% of cases. Delivery should take place in a tertiary centre with neonatal and paediatric surgical facilities. After birth, a nasogastric or orogastric tube is placed to decompress the stomach to minimize aspiration, and routine supportive management usually includes administration of intravenous fluids. Once clinically stable, surgical repair via laparotomy or laparoscopy is performed. Intraoperatively, it is important to exclude any associated malrotations, other small bowel atresia, or an annular pancreas. The long‐term prognosis for duodenal atresia is very good, with survival rates of approximately 90%.

Meconium ileus/peritonitis [10,11]

Meconium ileus is impaction of abnormally thick meconium in the distal ileum. Meconium peritonitis occurs when there is perforation of bowel in utero, resulting in a sterile chemical peritonitis. Ultrasound features of meconium peritonitis include intra‐abdominal calcifications, hyperechogenic bowel, ascites and bowel dilatation. Polyhydramnios may also be present. Serial ultrasound scans should be performed to assess progression of bowel dilatation, development of ascites or intra‐abdominal cysts and polyhydramnios, which might indicate complicated meconium peritonitis with a 50% chance of requiring neonatal surgery. If these are present, consideration should be given to delivering the baby in a tertiary centre with neonatal surgical facilities.

Parental cystic fibrosis carrier testing and/or invasive fetal testing should be offered. If cystic fibrosis is diagnosed, appropriate genetic counselling should be offered and termination of pregnancy discussed if the diagnosis is made early in pregnancy. Long‐term outcome depends on the underlying cause for the meconium peritonitis. In simple isolated meconium peritonitis the prognosis is usually excellent. In the simple form, thickened meconium begins to form in utero, and results in obstruction to the mid‐ileum that causes proximal dilatation, bowel wall thickening, and congestion. In complicated cases, thickened meconium and obstruction lead to complications such as segmental volvulus, atresia, necrosis, perforation, meconium peritonitis (generalized) and giant meconium pseudocyst formation. In infants with cystic fibrosis the long‐term outlook is guarded because of other extra‐abdominal complications that can develop.

Omphalocele (exomphalos) [12,13]

This is a midline anterior abdominal wall defect of variable size characterized by the absence of abdominal muscles, fascia and skin. It can occur in the upper, mid or lower abdomen. A defect in cranial folding results in a high or epigastric omphalocele, classically seen in pentalogy of Cantrell (epigastric omphalocele, anterior diaphragmatic defect, sternal cleft and pericardial/cardiac defects). Lateral folding defects result in a mid‐abdominal omphalocele and caudal defects cause a hypogastric omphalocele seen in bladder or cloacal exstrophy. The herniated viscera are covered by a membrane consisting of peritoneum on the inner surface, amnion on the outer surface and Wharton’s jelly between the two layers. The umbilical cord inserts into the sac and not the body wall. It has an incidence of 1.5–3 per 10 000 births. Omphaloceles may be stratified into three groups: small, giant or ruptured. A giant omphalocele is often described as one with an abdominal wall defect of more than 5 cm or with more than 50–75% of the liver within the sac. The larger the defect, the higher the risk of postnatal complications, such as pulmonary hypoplasia and respiratory insufficiency and an increased prevalence of neurodevelopmental delay.

Most cases of omphalocele are sporadic and associated with advanced maternal age. It may occur in isolation or associated with aneuploidy (40%) or as part of a genetic syndrome. If aneuploidy is present, trisomy 18 is the most common chromosome abnormality. Smaller defects are more likely to be associated with chromosome abnormalities. Associated abnormalities are common (50–70%), with cardiac lesions predominating (30–40% of cases). Fetal mortality is strongly associated with the presence of additional structural malformations. The diagnosis can be made in the first trimester, although most are detected at mid‐trimester anomaly scan. Maternal serum α‐fetoprotein is usually raised by an average of 4 multiples of the median.

Once the abnormality has been detected, the patient should be referred to a tertiary centre where there are facilities for detailed evaluation of the fetus. Karyotyping and fetal echocardiography should be performed. If macroglossia and other organomegaly are detected, Beckwith–Wiedemann syndrome should be suspected and the cytogenetics laboratory alerted to specifically look for abnormalities in the 11p15.5 region. Beckwith–Wiedemann syndrome is a growth disorder characterized by macroglossia, macrosomia, omphalocele, hypoglycaemia leading to seizures, visceromegaly, hemihyperplasia, renal abnormalities, ear creases and pits, nevus flammeus, and embryonic tumours (e.g. Wilms’ tumour, hepatoblastoma, neuroblastoma and rhabdomyosarcoma). Omphalocele may also be part of the OEIS (omphalocele, bladder exstrophy, imperforate anus, spina bifida) complex.

Multidisciplinary counselling with paediatric surgeons, neonatologists, paediatric cardiologists and fetal medicine specialists should take place. The parents should be advised about increased incidence of fetal growth restriction, preterm labour and intrauterine death. Delivery should take place in a tertiary centre. Although vaginal delivery is reasonable and does not appear to influence outcome, elective caesarean section may also be an option in order that delivery takes place in a more controlled environment and timing of neonatal surgery can be better planned. Large omphaloceles are probably best delivered by caesarean section because of the possibility of trauma or soft tissue dystocia during a vaginal delivery.

The aim of surgery is to reduce the herniated viscera into the abdomen and to close the fascia and skin to create a solid abdominal wall with a relatively normal umbilicus. However, treatment can vary depending on the size and type of defect, the size of the baby, and any associated neonatal problems. Many surgeons prefer primary closure whenever possible. However, large defects with significant visceral herniation may require a more gradual or phased approach using silos to achieve reduction over a period of time before the abdominal wall is finally closed.

Gastroschisis [12–14]

This anomaly is believed to result secondary to an ischaemic insult to the developing abdominal wall. A full‐thickness defect occurs secondary to incomplete closure of the lateral folds during the sixth week of gestation. The right paraumbilical area is usually affected. The incidence of gastroschisis is between 0.4 and 3 per 10 000 births and appears to be increasing. It has a strong association with young maternal age (<20 years), cigarette smoking, illicit drugs (cocaine), vasoactive over‐the‐counter drugs (such as pseudoephedrine) and environmental toxins. The diagnosis is usually obvious on ultrasound, often during the first‐trimester (11–14 weeks) nuchal translucency scan, with free floating bowel or rarely the liver floating in the amniotic fluid without a covering membrane. Differential diagnoses include ruptured omphalocele sac or limb–body wall complex.

Associated anomalies occur in 10–20% of cases and most of these are in the gastrointestinal tract. It has been proposed that gastroschisis should be classified as simple (if isolated) or as complex (if associated with intestinal atresia, perforation, stenosis or volvulus). Chromosomal abnormalities or genetic syndromes are very rare. There is a slight increase in the incidence of cardiac abnormalities but this is not as high as seen in omphalocele. There is an increased incidence of preterm labour (30%), fetal growth restriction (70%), oligohydramnios (25%) and fetal death (5%). The cause of fetal growth failure is unclear but could be partially due to increased protein loss from the exposed viscera. The herniated bowel is at risk from volvulus and long‐segment necrosis and/or more localized atretic and stenotic segments. Increasing bowel dilation, progressive oligohydramnios or decreased growth velocity may all be indicative of a fetus that is at increased risk of intrauterine death or greater neonatal complications. Early referral to a tertiary centre with multidisciplinary management is essential. Fetal echocardiography should be performed due to the increased association with cardiac anomalies. Serial scans should be performed to assess fetal growth and liquor volume, degree of bowel dilatation and bowel wall thickness. There is no contraindication for vaginal delivery but, as for omphalocele, elective caesarean section may also be an option to facilitate neonatal care. Bladder herniation and significant bowel dilatation may be risk factors for intrapartum fetal compromise (fetal distress) requiring operative delivery. Most centres now advocate delivery by 37 weeks given the increased risk of fetal demise after this gestation.

The ideal treatment of gastroschisis is immediate reduction of the herniated bowel back into the abdominal cavity and closure of the abdominal wall (primary reduction and repair). However, if reduction is likely to cause an abdominal compartment syndrome or significant respiratory difficulty, then staged repair is preferred. This involves applying a plastic silo around the bowel to progressively push the herniated viscera into the abdominal cavity over a number of days until definitive closure is possible. Overall survival is good (90–95%), with most deaths occurring in babies who have significant bowel loss, sepsis or long‐term complications of short bowel syndrome. There is a 10% risk of hypoperistalsis syndrome, which may require longer hospitalization and hyperalimentation. Gastrointestinal reflux occurs in 10% of cases and there is a 5–10% risk of obstruction due to adhesions in the longer term. A significant number of cases will also develop inguinal hernias due to increased intra‐abdominal pressure post surgery. The risk of recurrence is small but exposure to vasoactive substances should be avoided in any subsequent pregnancy.

Renal agenesis [17,18]

Unilateral renal agenesis has an incidence of 1 in 500–1000 births compared with bilateral renal agenesis, which occurs in 1 in 5000–10 000 births. Bilateral renal agenesis is not compatible with extrauterine life. It occurs more commonly in males and there is also an increased incidence in twins. Poorly controlled maternal diabetes or ingestion of renotoxic drugs are other aetiological factors. The diagnosis is usually made at the mid‐trimester fetal anomaly scan. Although earlier diagnosis is sometimes possible, it is often difficult in the first trimester as the amniotic fluid volume is not significantly reduced at that stage. Anhydramnios is usually present by mid‐trimester in bilateral renal agenesis. The liquor volume is usually normal in unilateral agenesis and the normal kidney can be larger due to compensatory hypertrophy.

There is an increased incidence of additional anomalies, particularly in the genital (blind vagina, uterine malformations, seminal vesicle cysts), cardiovascular and gastrointestinal systems in up to 44% of fetuses with renal agenesis. If the diagnosis of bilateral renal agenesis is made antenatally, the parents must be counselled about the dismal outcome and offered termination of pregnancy. Karyotyping and post‐mortem is essential to help diagnose aneuploidy or a specific syndrome. Ultrasound of parental kidneys should be considered and genetic counselling offered. The risk of recurrence is low in unilateral renal agenesis (2–4%) but can be as high as 6–10% in bilateral cases.

Multicystic dysplastic kidney [19,20]

Unilateral multicystic dysplastic kidney (MCDK) has an incidence of 1 in 3000–5000 live births compared with 1 in 10 000 for bilateral dysplasia. It is one of the commonest causes of an abdominal mass in the neonatal period. The abnormal kidneys contain undifferentiated cells and metaplastic elements such as cartilage. On ultrasound, large hyperechogenic kidneys containing multiple cysts of varying sizes are present. Contralateral renal abnormalities can occur in 30–50% of cases. The prognosis for the fetus depends on whether there is unilateral or bilateral dysplasia. Bilateral MCDK is often lethal, with fetuses dying from pulmonary hypoplasia after birth. Termination of pregnancy should be offered in these cases.

No specific fetal intervention is required in cases of isolated unilateral MCDK. Serial ultrasound scans to monitor size of the abnormal kidney and liquor volume should be performed. Occasionally, gradual resorption (autonephrectomy) of the abnormal kidney can occur. Karyotyping should be offered to exclude aneuploidy. The mode of delivery is based on standard obstetric criteria. The prognosis is usually good. There is a small risk of long‐term hypertension and malignant transformation in the dysplastic kidney. Children with a normal solitary functioning kidney, with evidence of compensatory hypertrophy, have a small risk of future renal insufficiency. In addition, there is an increased risk of hyperfiltration injury, which may be marked by hypertension and proteinuria that warrants long‐term surveillance. Children with MCDK have a higher risk of vesico‐ureteric reflux compared with the general population, particularly if there are contralateral renal abnormalities. There is also a risk of abnormalities of the internal genitalia for both males and females with MCDK.

Lower urinary tract obstruction [21]

In male fetuses, posterior urethral valves are the most common cause (90%) of bladder outlet obstruction. In female fetuses, urethral atresia accounts for the majority of cases. Less common causes of congenital lower urinary tract obstruction include anterior urethral valves/anterior urethral diverticulum, prune belly syndrome, urethral atresia, prolapsed ureterocoele, syringocoele, megalourethra, megacystis–microcolon–hypoperistalsis syndrome, obstruction by a hydrocolpos in females with cloacal anomalies, or rarely obstruction by a tumour such as a sacrococcygeal teratoma.

Oligohydramnios and a large thick‐walled bladder with a keyhole sign and bilateral hydroureters and hydronephrosis are usually evident on ultrasound. The prognosis is worse (95% mortality) in those diagnosed antenatally when mid‐trimester oligohydramnios is present. Features that suggest poor prognosis include dilatation of the upper tract, increased bladder wall thickness, oligohydramnios and evidence of renal dysplasia (echogenic renal cortex and cystic renal change), especially before 24 weeks. Obstruction can be complete or partial and the amount of liquor volume usually gives some idea as to the severity of the obstruction. In complete obstruction anhydramnios rapidly develops. In addition, renal dysplasia can occur from an early gestation if the obstruction is severe. Karyotyping is important as aneuploidy is present in up to 10% of cases. Termination of pregnancy is an option, particularly if there is severe oligohydramnios/anhydramnios, the diagnosis is made early in pregnancy or if there is evidence of renal dysplasia on ultrasound.

Fetal therapy is possible and includes serial vesicocentesis, percutaneous vesico‐amniotic shunting (VAS) or cystoscopy. The rationale for VAS is to decompress the urinary tract and therefore relieve the back‐pressure on the fetal kidneys and to hopefully prevent the development of renal dysplasia. Shunting also allows restoration of flow of fetal urine into the amniotic cavity and thus prevents pulmonary hypoplasia. Compared with VAS, fetal cystoscopy for cases with posterior urethral valves appears to be more effective in improving both the 6’month survival rate and renal function, while VAS was only associated with improvement in the 6‐month survival rate with no effect on renal function. Fetal cystoscopy is more invasive than VAS and carries a 10% urological fistula rate following fetal laser ablation of the bladder outlet obstruction. The risk of requiring dialysis and subsequent renal failure is approximately 30–50% in several series. To date, fetal intervention has not significantly changed the long‐term renal outcome for affected individuals. Additional long‐term problems include reflux, recurrent infections, bladder compliance and voiding issues and sexual function.

Cleft lip and palate [22–24]

The incidence of cleft lip and palate varies with ethnicity and geographical region but in a Caucasian population it is approximately 1 in 800–1000 for cleft lip and palate and 1 in 100 for cleft palate alone. Orofacial clefts can be classified as non‐syndromic (isolated) or syndromic based on the presence of other congenital anomalies. Approximately 20–50% of all orofacial clefts are believed to be syndromic. The diagnosis is often made following the mid‐trimester fetal anomaly scan. Fetal three‐dimensional ultrasound and/or fetal MRI may help in determining the extent of palatal involvement. The aetiology of cleft lip/cleft palate is complex and multifactorial, involving both genetic and environmental factors. Many environmental factors are associated with orofacial clefting, including maternal alcohol consumption and cigarette smoking. Folate deficiency is also associated with cleft lip/cleft palate and prenatal folic acid supplementation has been shown to decrease this risk. Maternal corticosteroid use causes a threefold to fourfold increase in orofacial clefting. Anticonvulsants, including phenytoin and valproic acid, also cause cleft lip and palate. Phenytoin causes a nearly 10‐fold increase in the incidence of facial clefting.

Associated anomalies include brain, cardiac and limb/spine deformities. There is a high risk of cerebral anomaly with midline clefts. Karyotyping should be offered in all cases. All patients should be referred to a multidisciplinary craniofacial team early following fetal diagnosis, where all aspects of the baby’s management including feeding, surgery and cosmetic results can be discussed with parents. It is important to exclude any underlying syndrome after birth and genetic counselling for the risk of recurrence should be offered.

Cystic hygroma/lymphangioma [25,26]

Cystic hygroma is a rare congenital malformation of the lymphatic system and has an incidence of between 1 in 6000 and 1 in 16 000 births. Among aborted fetuses the incidence may be as high as 1 in 300. Approximately 75% occur in the neck, usually in the posterior triangle more commonly on the left side, and 20% occur in the axillary region. Chromosome abnormalities are present in almost 70% of cases, with Turner’s syndrome and Down’s syndrome particularly common. There is also an association with non‐chromosomal conditions (Noonan’s syndrome, multiple pterygium syndrome). Once detected, a careful search for additional abnormalities is vital. Karyotyping should always be offered. The presence of hydrops is a poor prognostic feature, with a perinatal mortality rate exceeding 80%. Fetal echocardiography should be performed. There is an increased incidence of preterm labour and polyhydramnios, particularly if the cystic hygroma impairs fetal swallowing. In very large lesions, obstruction of the pharynx and larynx may develop making intubation very difficult. The EXIT procedure (ex‐utero intrapartum treatment) may be required before the umbilical cord is divided.

Diaphragmatic hernia [27,28]

Congenital diaphragmatic hernia has an incidence of 1 in 3000–5000 births. It occurs more commonly on the left side (75–80%) than on the right side (20–25%). The combination of lung hypoplasia, lung immaturity and pulmonary hypertension and the presence of other malformations can result in high mortality for this condition. The degree of pulmonary hypoplasia depends entirely on the length of time and extent the herniated organs have compressed the fetal lungs. Associated abnormalities may be present in 30–60% of cases and can involve any organ system. Aneuploidy is present in 10–20% of cases and it may also be associated with some genetic syndromes (Fryn’s syndrome, Beckwith–Wiedemann syndrome). Congenital diaphragmatic hernia should be suspected if the fetal stomach is not in its usual intra‐abdominal position. Liver, mesentery and bowel and spleen may be present in the chest. Differential diagnoses include congenital cystic adenomatoid malformations, bronchogenic cysts, pulmonary sequestration or thoracic teratomas. Polyhydramnios and/or hydrops may sometimes be present. Increased liquor is usually due to impaired swallowing and hydrops may occur if there is significant cardiac compression. Liver herniation is a poor predictive factor for the development of pulmonary hypoplasia.

Management includes detailed assessment of the fetus for additional anomalies, karyotyping and fetal echocardiography. Fetal MRI or three‐dimensional ultrasound can sometimes be considered to evaluate lung volume. Parents should be counselled by a paediatric surgeon regarding neonatal management. Termination of pregnancy is an option if significant visceral herniation (particularly liver) is present. The aim is to deliver at term. The mode of delivery is determined on standard obstetric criteria. However, it is essential that delivery takes place in a tertiary centre where the baby can be closely monitored to assess the degree of pulmonary compromise (hypoplasia and vascular hypertension) before surgery is undertaken. Prenatal intervention by fetoscopic endoluminal tracheal occlusion (FETO) is now an option, with the main objective of improving fetal lung growth. There is evidence that treatment in utero can increase postnatal survival for both left‐ and right‐sided defects. However, prenatal treatment, only available in select fetal therapy centres, is associated with significant risk of preterm premature rupture of membranes and preterm birth.

Congenital pulmonary airway malformation [29–31]

Congenital pulmonary airway malformations (CPAMs), previously known as congenital cystic adenomatoid malformations, are rare developmental malformations of the lower respiratory tract. CPAMs account for 95% of congenital cystic lung abnormalities and are the most common cystic lung lesions diagnosed by prenatal screening. They are characterized by lack of normal alveoli and excessive proliferation and cystic dilatation of terminal respiratory bronchioles. The incidence of CPAM is between 1 in 11 000 and 1 in 35 000 live births and is slightly more common in males. They are usually unilateral (>85%) and usually involve only one lobe of the lung. Most (60%) are left‐sided lesions. The diagnosis is usually made on antenatal ultrasound by the detection of enlarged hyperechogenic lungs sometimes containing cysts of varying sizes. Mediastinal shift, cardiac compression, polyhydramnios and hydrops may also be present. Between 45 and 85% of prenatally identified CPAMs will spontaneously regress. However, large macrocystic or solid lesions can cause hydrops, pulmonary hypoplasia, cardiac dysfunction and perinatal death. The majority of lesions follow a characteristic growth pattern that is highly dependent on gestational age. There is usually an increase in size between 17 and 26 weeks before possible regression after 30 weeks. Large lesions can cause pulmonary hypoplasia, impairment of fetal swallowing and polyhydramnios, cardiac compression and hydrops. Serial scans are essential to monitor the size of the lesion (particularly macrocystic CPAM), the development of cardiac compression and/or hydrops. Prenatal treatment options include the maternal administration of steroids, minimally invasive procedures or, rarely, open fetal surgery. These interventions aim to alleviate the mass effect, prevent the progression of complications and improve the outcome for these fetuses. In selected macrocystic lesions, fetal therapy (either aspiration of the cyst or insertion of a shunt to drain the cyst) may be an option. Maternal steroid treatment has been reported to have a beneficial effect on large microcystic CPAMs. The mode and timing of delivery is on standard obstetric criteria. Postnatally, the baby will require careful monitoring and a chest X‐ray. Surgery may be deferred for up to 24 months.

Pleural effusions [32,33]

Fetal pleural effusions have an incidence of between 1 in 10 000 and 1 in 15 000 pregnancies. Effusions may be primary (due to leak of chyle into the pleural cavity) or secondary (seen in hydrops). Complications include mediastinal shift, cardiac compression, hydrops and pulmonary hypoplasia. Affected fetuses are at significant risk for respiratory distress at birth. Once detected the patient should be referred to a fetal medicine unit for further investigations. The presence of other anomalies should be excluded. Fetal echocardiography should be performed as cardiac abnormalities are present in 5% of cases. Karyotyping should be offered as there is a significant association (10%) with aneuploidy. Maternal serology for infection should be performed. Serial scans should be arranged to assess the size of the effusion and for the development of hydrops or polyhydramnios as these are poor prognostic features. There are several treatment options. Firstly, a period of expectant observation is reasonable if the fetus is not hydropic and the effusion is small or moderate in size. Thoracocentesis or pleuro‐amniotic shunting are other options. The risks associated with pleuro‐amniotic shunting include miscarriage or preterm labour, rupture of membranes, blockage of the shunt and shunt migration. Survival after pleuro‐amniotic shunting is approximately 80%.