Antenatal diagnosis has become available for an increasing number of disorders. Screening tests performed on maternal blood and ultrasound of the fetus are listed in Box 9.1. The main diagnostic techniques for antenatal diagnosis are maternal serum screening, detailed ultrasound scanning, chorionic villus sampling (at >10 weeks of pregnancy) and amniocentesis (>15 weeks) (Fig. 9.1). In some rare conditions, preimplantation genetic diagnosis (PGD) allows genetic analysis of cells from a developing embryo before transfer to the uterus. The structural malformations and other lesions which can be identified on ultrasound are listed in Box 9.2, with an example in Figure 9.2.

Box 9.1 Screening tests for antenatal diagnosis

Maternal blood

Blood group and antibodies – for rhesus and other red cell incompatibilities

Hepatitis B

Syphilis

Rubella

HIV infection

Neural tube defects – raised maternal serum alphafetoprotein (MSAFP) with spina bifida or anencephaly, but ultrasound alone increasingly used

Down syndrome – risk estimate calculated from age, biochemical markers combined with ultrasound screening for nuchal translucency (back of neck). Aim is to detect >75% with <3% false-positive rate. If high risk, fetal chromosome analysis is offered

Ultrasound screening

Gestational age – can be estimated reliably if early in pregnancy

Multiple pregnancies – can be identified

Structural malformation – 50–70% of major congenital malformations can be detected. If a significant abnormality is suspected, a more detailed scan by a specialist is indicated

Fetal growth – can be monitored by serial measurement of abdominal circumference, head circumference and femur length

Amniotic fluid volume – oligohydramnios may result from reduced fetal urine production (because of dysplastic or absent kidneys or obstructive uropathy), from prolonged rupture of the membranes or associated with severe intrauterine growth restriction. It may cause pulmonary hypoplasia and limb and facial deformities from pressure on the fetus (Potter syndrome)

Polyhydramnios – is associated with maternal diabetes and structural gastrointestinal abnormalities, e.g. atresia in the fetus

Box 9.2 Main structural malformations and other lesions detectable by ultrasound

CNS	Anencephaly – always detected
	Spina bifida
	Hydrocephalus, microcephaly, encephalocele
Cardiac	About 50% of severe malformations detected on ‘routine’ screening, over 90% at specialist centres
Intrathoracica	Diaphragmatic hernia, congenital cystadenomatoid lung malformation (CCAM) Oesophageal atresia
Facial	Cleft lip
Gastrointestinal	Bowel obstruction, e.g. duodenal atresia
	Exomphalos and gastroschisis
Genitourinary	Dysplastic or cystic kidneys
	Obstructive disorders of kidneys or urinary tract (hydronephrosis, distended bladder)
Skeletal	Skeletal dysplasias, e.g. achondroplasia and limb reduction deformities
Hydrops	Oedema of the skin, pleural effusions and ascites
Chromosomal	Down syndrome – suspected from thickened back of neck (nuchal translucency), duodenal atresia or an atrioventricular canal defect of the heart. Other chromosomal disorders – from identifying multiple abnormalities

Figure 9.1 Some of the techniques used for antenatal diagnosis.

Antenatal screening for disorders affecting the mother or fetus allows:

• reassurance where disorders are not detected

• optimal obstetric management of the mother and fetus

• interventions for a limited number of conditions, such as relieving bladder obstruction or draining pleural effusions, to improve perinatal outcome

• counselling and neonatal management to be planned in advance

• the option of termination of pregnancy to be offered for severe disorders affecting the fetus (see Case History 9.1) or compromising maternal health.

Parents require accurate medical advice and counselling to help them with these difficult decisions. Many transient or minor structural disorders of the fetus are also detected, which may cause considerable anxiety.

Antenatal diagnosis allows many congenital malformations which used to be diagnosed at birth or during infancy to be identified before birth.

Fetal medicine

The fetus can sometimes be treated by giving medication to the mother. Examples include:

• Glucocorticoid therapy before preterm delivery accelerates lung maturity and surfactant production. This has been tested in over 15 randomised trials and markedly reduces the incidence of respiratory distress syndrome (RDS) (relative risk 0.66), of intraventricular haemorrhage (relative risk 0.54) and neonatal mortality (relative risk 0.69) in preterm infants. For optimal effect, a completed course needs to be given at least 24 h before delivery.

• Digoxin or flecainide can be given to the mother to treat fetal supraventricular tachycardia.

Example of antenatal diagnosis-gastroschisis

Figure 9.2 Gastroschisis on antenatal ultrasound showing free loops of small bowel in the amniotic fluid **(a)** and following delivery **(b)**. Antenatal diagnosis allowed the baby to be delivered at a paediatric surgical unit and the parents to be forewarned about the need for surgery. Satisfactory surgical repair was achieved. (Courtesy of Mr Karl Murphy.)

Case History

9.1 Antenatal diagnosis

A routine ultrasound scan at 18 weeks’ gestation identified an abnormal ‘lemon-shaped’ skull (Fig. 9.3). This, together with an abnormal appearance of the cerebellum, is the Arnold–Chiari malformation, which is associated with spina bifida. An extensive spinal defect was confirmed on ultrasound. Dilatation of the cerebral ventricles and talipes already present in this fetus suggested a severe spinal lesion. After counselling, the parents decided to terminate the pregnancy.

Figure 9.3 Transverse section showing a ‘lemon-shaped’ skull on ultrasound instead of the normal oval shape. This is associated with spina bifida. (Courtesy of Mr Guy Thorpe-Beeston.)

There are a few conditions where therapy can be given to the fetus directly:

• Rhesus isoimmunisation. Severely affected fetuses become anaemic and may develop hydrops fetalis, with oedema and ascites. Infants at risk are identified by maternal antibody screening. Regular ultrasound of the fetus is performed to detect fetal anaemia non-invasively using Doppler velocimetry of the fetal middle cerebral artery. Fetal blood transfusion via the umbilical vein may be required regularly from about 20 weeks’ gestation. The incidence of rhesus haemolytic disease has fallen markedly since anti-D immunisation of mothers was introduced but hydrops fetalis is still seen due to other red blood cell antibodies such as Kell.

• Perinatal isoimmune thrombocytopenia. This condition is analogous to rhesus isoimmunisation but involves maternal antiplatelet antibodies crossing the placenta. It is rare, affecting about 1 in 5000 births. Intracranial haemorrhage secondary to fetal thrombocytopenia occurs in up to 25%. The problem may be anticipated if there was a previously affected infant, when prenatal intravenous immunoglobulin can be given or repeated intrauterine platelet transfusions performed.

Maternal glucocorticoid therapy before preterm delivery markedly reduces morbidity and mortality in the neonate.

Fetal surgery

Fetal surgery is a relatively new development with varying results. Procedures which have been performed include:

• Catheter shunts inserted under ultrasound guidance. This is to drain fetal pleural effusions (pleuro-amniotic shunts), often from a chylothorax (lymphatic fluid) or congenital cystic adenomatous malformation of the lung. One end of a looped catheter lies in the chest, the other end in the amniotic cavity.

• Laser therapy to ablate placental anastomoses which lead to the twin–twin transfusion syndrome (TTTS)

• Intrauterine shunting for obstruction to urinary outflow as with posterior urethral valves

• Dilatation of stenotic heart valves via a transabdominal catheter inserted under ultrasound guidance into the fetal heart. Results appear promising

• Endotracheal balloon occlusion for congenital diaphragmatic hernia, as tracheal obstruction in utero may promote lung growth

• Surgical correction by hysterotomy. This is when the uterus is opened at 22–24 weeks’ gestation. It has been performed in a few specialist centres for spina bifida but may precipitate preterm delivery and its efficacy remains highly uncertain. Results of fetal surgery to close spina bifida suggest that hydrocephalus may be reduced but does not improve the prognosis of the spinal lesion.

Outcome has mostly been very poor because of the severity of the conditions treated. Careful case selection and follow-up are required to ensure that these novel forms of treatment are of long-term benefit.

Obstetric conditions affecting the fetus

Maternal conditions affecting the fetus

Diabetes mellitus

Women with insulin-dependent diabetes find it more difficult to maintain good diabetic control during pregnancy and have an increased insulin requirement. Poorly-controlled maternal diabetes is associated with polyhydramnios and pre-eclampsia, increased rate of early fetal loss, congenital malformations and late unexplained intrauterine death. Ketoacidosis carries a high fetal mortality. With meticulous attention to diabetic control, the perinatal mortality rate is now only slightly greater than in non-diabetics. The National Institute for Health and Clinical Excellence (NICE) has produced guidance on the management of diabetes and its complications from preconception to the postnatal period. The emphasis is on aiming for good control of blood glucose.

Fetal problems associated with maternal diabetes are:

• Congenital malformations. Overall, there is a 6% risk of congenital malformations, a three-fold increase compared with the non-diabetic population. The range of anomalies is similar to that for the general population, apart from an increased incidence of cardiac malformations, sacral agenesis (caudal regression syndrome) and hypoplastic left colon, although the latter two conditions are rare. Studies show that good diabetic control periconceptionally reduces the risk of congenital malformations.

• Intrauterine growth restriction (IUGR). There is a three-fold increase in growth restriction in mothers with long-standing microvascular disease.

• Macrosomia (Fig. 9.4). Maternal hyperglycaemia causes fetal hyperglycaemia as glucose crosses the placenta. As insulin does not cross the placenta, the fetus responds with increased secretion of insulin, which promotes growth by increasing both cell number and size. About 25% of such infants have a birthweight greater than 4 kg compared with 8% of non-diabetics. The macrosomia predisposes to cephalopelvic disproportion, birth asphyxia, shoulder dystocia and brachial plexus injury.