The overall incidence in the UK has fallen over the past three decades due to the introduction of screening programmes in pregnancy, the resultant greater success at diagnosis during pregnancy and parents opting to terminate a pregnancy once a severe abnormality has been diagnosed.

The commonest four groups of defects are neural tube defects (3–7/1000), congenital cardiac defects (6/1000), Down’s syndrome (1.5/1000) and cleft lip/palate (1.5/1000) (Table 10.1).

Table 10.1

Major congenital abnormalities

Abnormality	Approximate incidence (per 1000 births)
Neural tube defects	3–7
Congenital heart disease	6
Severe mental retardation	4
Down’s syndrome	1.5
Cleft lip/palate	1.5
Talipes	1–2
Abnormalities of limbs	1–2
Deafness	0.8
Blindness	0.2
Others, including urinary tract anomalies	2
Total	15–30

Neural tube defects

The neural tube defects are the commonest of the major congenital abnormalities and include anencephaly, microcephaly, spina bifida with or without myelomeningocele, encephalocele, holoprosencephaly and hydranencephaly (Fig. 10.1). The incidence is approximately 1/200 and the chance of having an affected child after one previous abnormal child is 1/20. Infants with anencephaly or microcephaly do not usually survive. Many die during labour and the remainder within the first week of life. Infants with open neural tube defects often survive, particularly where it is possible to cover the lesion surgically with skin. However, the defect may result in paraplegia and bowel and bladder incontinence. The child often has normal intelligence and becomes aware of the problems posed for the parents. Closed lesions generally do not cause problems and may escape detection until after birth.

Fig. 10.1 Two common abnormalities of the central nervous system. (A) Anencephaly. (B) Spina bifida with open neural tube defect.

There is good evidence that pre- and periconceptual folic acid supplementation (400 µg/day) reduces the incidence of this condition. Once a woman is pregnant, the major effort is directed toward screening techniques that enable recognition of the abnormality and the offer of a termination of the pregnancy where there is a lethal abnormality.

Folic acid dietary supplementation is indicated both before and during pregnancy in those women who have experienced a pregnancy complicated by a neural tube defect.

Congenital cardiac defects

Some of these infants present with intrauterine growth retardation and oligohydramnios, but in many cases the diagnosis is recognised and diagnosed after delivery. With improvements in real-time ultrasound imaging, recognition of many cardiac defects has become possible; however, early recognition is essential if any action is to be taken. A four-chamber view of the fetal heart is shown in Figure 10.2.

Fig. 10.2 Four-chamber ultrasound view of the fetal heart.

The most common defects are ventricular and atrial septal defects, pulmonary and aortic stenosis, coarctation and transpositions, including the tetralogy of Fallot. These lesions can generally now be recognized on the four-chamber views recorded during detailed 18-week gestation scans.

Defects of the abdominal wall

Defects of the abdominal wall can be diagnosed by ultrasound imaging. They include gastroschisis and exomphalos (Fig. 10.3). In both cases, the bowel extrudes outside the abdominal cavity. The main differences between the two are that a gastroschisis is a defect that is separate from the umbilical cord (usually 2–3 cm below and to the right), does not have a peritoneal covering and is usually an isolated problem. In contrast, an exomphalos is essentially a large hernia of the umbilical cord with a peritoneal covering and an increased risk of an underlying chromosomal abnormality,

Fig. 10.3 Bowel extrusion associated with exomphalos.

Chromosomal abnormalities

A considerable number of chromosomal abnormalities have been identified from the culture and karyotyping of fetal/placental cells in the amniotic fluid or from the chorionic plate. The chromosomal abnormalities include both structural and numerical abnormalities of the karyotype. The commonest abnormality is that associated with trisomy 21 or Down’s syndrome.

Down’s syndrome

Down’s syndrome (DS) is characterized by the typical abnormal facial features (Fig 10.4), mental retardation of varying degrees of severity and congenital heart disease. The karyotype includes an additional chromosome on group 21 (‘trisomy 21’; Fig 10.5). The incidence overall is 1.5/1000 births. However, the risk increases with advancing maternal age (see below). The underlying reason is thought to be an increased frequency of non-disjunction at meiosis.

About 6–8% of affected infants have the disease as a result of a translocation and the extra 21 chromosome carried on to another chromosome, usually in group 13–15. The mother or the father will usually show evidence of being a balanced translocation carrier.

Assessing fetal normality

Screening

Screening in this context is the process whereby women with a higher risk of fetal abnormality are identified in the general population. This screening is undertaken using identification of clinical risk factors, ultrasound (US) and biochemical testing of maternal serum. Clinical risk factors can be identified throughout pregnancy though the options for management are different depending on the gestational age. US and biochemical screening is offered to women in the first half of pregnancy. Ideally women should be offered a combined screening test (using US and biochemistry) for DS towards the end of the first trimester and a detailed US scan at about 20 weeks. The early scan also allows gestational age to be confirmed. If a woman presents too late for the first trimester DS screening, then she should be offered a biochemical screening test at about 16 weeks.

Clinical risk factors: early pregnancy

These include:

• maternal age and risk of aneuploidy especially DS (see Tables 10.2 and 10.3).

Table 10.2

The risk of having a pregnancy affected by Down’s syndrome according to maternal age at the time of birth

Maternal age at delivery (years)	Risk of Down’s syndrome
15	1 : 1578
20	1 : 1528
25	1 : 1351
30	1 : 909
31	1 : 796
32	1 : 683
33	1 : 574
34	1 : 474
35	1 : 384
36	1 : 307
37	1 : 242
38	1 : 189
39	1 : 146
40	1 : 112
41	1 : 85
42	1 : 65
43	1 : 49
44	1 : 37
45	1 : 28
46	1 : 21
47	1 : 15
48	1 : 11
49	1 : 8
50	1 : 6

Table 10.3

Chromosomal abnormalities by maternal age at the time of amniocentesis performed at 16 weeks’ gestation (expressed as rate per 1000)

Maternal age (years)	Trisomy 21	Trisomy 18	Trisomy 13	XXY	All chromosomal anomalies
35	3.9	0.5	0.2	0.5	8.7
36	5.0	0.7	0.3	0.6	10.1
37	6.4	1.0	0.4	0.8	12.2
38	8.1	1.4	0.5	1.1	14.8
39	10.4	2.0	0.8	1.4	18.4
40	13.3	2.8	1.1	1.8	23.0
41	16.9	3.9	1.5	2.4	29.0
42	21.6	5.5	2.1	3.1	37.0
43	27.4	7.6		4.1	45.0
44	34.8			5.4	50.0
45	44.2			7.0	62.0
46	55.9			9.1	77.0
47	70.4			11.9	96.0

• maternal drug ingestion:

anticonvulsant drugs (e.g. phenytoin, carbamazepine and sodium valproate) that can produce defects of the central nervous system especially neural tube defects

cytotoxic agents used in cancer therapy or for immunosuppression with organ transplantation are associated with an increased risk of fetal growth restriction

warfarin is teratogenic when used in the first trimester and can produce a fetal bleeding disorder when used later in pregnancy

• previous history of fetal abnormality:

if, for example, a woman has had a DS baby in the past she is at greater risk of recurrence than the risk given by her age alone

however, not all fetal abnormalities are associated with a greater risk of recurrence in a subsequent pregnancy

• maternal disease (see Chapter 9) including:

diabetes: the reported risks of fetal abnormality vary between 3–8%. This figure is reduced significantly if the diabetes is well controlled before and during the first trimester

congenital heart cardiac disease: a woman who has a congenital cardiac defect has a 1–2% risk of a cardiac abnormality in her fetus.

Management options with an ‘abnormal’ or ‘positive’ test

Further counselling

Women (with their partner) with an abnormal/positive test should be seen as soon as possible by a health professional with the appropriate expertise and training for ongoing counselling and management. This will either be an obstetrician with a special interest in fetal problems or a fetal medicine subspecialist. The first priority is for the woman and her partner to have non-directive counselling covering:

• what they have been told

• what they think the abnormal/positive test means

• what the abnormal/positive test actually means

• what the options are.

Further assessment

It may be appropriate for the couple to consider further assessment in the form of:

• For women with an increased risk of a chromosomal abnormality, an invasive test such as a chorionic villus biopsy/sampling (Fig. 10.7) if the woman presents in the first trimester or an amniocentesis (Fig. 10.8) if the woman presents in the second trimester. Before undertaking the procedure, the woman should be informed that it is undertaken aseptically, will provide information about chromosome number and structure but that it carries a risk of miscarriage (about 1%).

Fig. 10.7 Chorionic villus sampling (US visualization is mandatory and undertaken in a similar way to that shown for amniocentesis in Fig 10.8A).

Fig. 10.8 Amniocentesis. (A) Simultaneous ultrasound (US) visualization; (B) US image with needle (arrow).

• For women suspected to have a structural fetal abnormality, further imaging to clarify the diagnosis either in the form of further US examinations after 1–2 weeks (to allow for fetal growth and better visualization of fetal anatomy) or an MRI scan (especially useful with abnormalities of the central nervous system). If the anatomical appearances suggest the fetus has a chromosomal abnormality, a CVS (which is more accurately termed placental biopsy at this stage of pregnancy) or amniocentesis could be offered.

Options for pregnancy

Once a fetal abnormality is diagnosed with a high chance of death or serious disability, after counselling, the parents may feel that they do not wish to continue with the pregnancy and opt for a termination. However, faced with the same facts other parents may decide to continue with the pregnancy. The decision is for the parents to make and no one else, hence the need for ‘non-directive’ counselling.

Possible interventions

With some fetal abnormalities a woman and her partner may be offered interventions aimed at improving or ameliorating the fetal condition. Examples include:

• Maternally administered anti-arrhythmic drugs to treat fetal cardiac arrhythmias.

• Insertion of a vesicoamniotic drain into the fetal bladder to by-pass urethral obstruction in cases of urethral valves to prevent further renal back-pressure and damage.

Surveillance in pregnancy

All women who decide to continue with the pregnancy with a fetal abnormality will need to be seen regularly for support and counselling by a small number of health professionals who are aware of the diagnosis. In specific cases there will be a need to undertake regular US examinations to assess whether complications of the abnormality are developing and warrant intervention (see above).

Delivery issues

Delivery issues may include:

• In advance of the delivery deciding on the place of birth on the basis of the baby’s likely need of resources after birth, e.g. neonatal intensive care or surgery, and arranging for the relevant neonatal medical professionals to meet the parents.

• Arranging elective delivery if it is considered desirable that the baby would benefit from delivery during the working day and week when full neonatal resources are available.

• With some fetal abnormalities it is preferable to avoid a vaginal birth, e.g. there may be a greater risk of fetal trauma such as in a case of fetal hydrocephalus.

Assessing the health of a normally formed fetus

Screening for fetal health

In contrast to the screening offered to pregnant women to assess their risk of fetal abnormality, what is offered to identify the unhealthy fetus is limited. It relies initially on identification of clinical risk factors associated with a greater risk of fetal compromise. Women with no risk factors for fetal compromise (‘low risk’) have:

• Maternal vigilance for fetal activity over second half of pregnancy.

• Fundal height measurement at every antenatal clinic visit. This involves measuring the distance between the maternal symphysis pubis and uterine fundus (see Fig. 6.12). The reverse blank side of tape measure uppermost and the distance (in cm) is read after it has been determined by turning the tape measure over. The normal range between 16–36 weeks is (gestational age in ±3 cm). Thus at 32 weeks the normal range is 32 ± 3 cm.

• Auscultation of the fetal heart at every antenatal clinic visit. This is undertaken either using a pinard stethoscope (Fig. 10.9A) or a handheld Doppler US device (Fig. 10.9B). In routine practice, the rate is not recorded just a note that the fetal heart is beating. Thus, abnormalities of the fetal baseline heart rate may be missed.

Fig. 10.9 Auscultation of the fetal heart (the aim is to place the stethoscope/transducer as close to the fetal heart as possible). If the fetal back is anterior the best site is over the left fetal scapula. If the fetal back is posterior the best site is around the maternal umbilicus). (A) Using the pinard stethoscope; (B) using a handheld Doppler US recording device.

Women with risk factors (‘high risk’) have customized surveillance that is determined by the presumed underlying pathophysiological process. The more common examples are shown in Table 10.4.

Table 10.4

Risk factors for fetal compromise

Type of risk	Risk factor/problem	Presumed pathophysiology	Surveillance
Specific	Maternal vascular disease, e.g. hypertension, antiphospholipid or lupus antibodies	Uteroplacental vascular disease (UPVD), i.e. poor blood flow to and within the placenta with associated reduced gaseous and nutritional transfer	Maternal vigilance for fetal movements Umbilical artery Doppler recordings US monitoring of fetal growth Biophysical assessment if any of these not normal
	Maternal diabetes	The pathophysiology of fetal risk is uncertain	The same package of surveillance is used as in women with UPVD, but it is less effective at predicting fetal death
	Twins	Main risks are: For all twins: fetal growth restriction form UPVD For monochorionic twins: the twin–twin transfusion syndrome (TTTS), i.e. shared placental circulation with risk of one fetus being the ‘donor’ and the other being the ‘recipient’	For fetal growth restriction: • Fetal surveillance as in women at risk of UPVD (see above) For TTTS, monitoring of monochorionic twins to look for signs of TTTS: • Amniotic fluid volume (AFV) raised in one twin (recipient) and reduced in the other (donor) • Absence of urine in fetal bladders • Abnormal umbilical artery Doppler recording in either fetus
	Isoimmunization due to Rhesus antibodies	Transplacental passage of maternal antibodies (anti-D or Kell or Duffy) causing severe fetal anaemia	With fetal anaemia the fetal middle cerebral artery blood flow is raised with anaemia and confirmed by fetal blood sampling (FBS)
Non-specific	Previous fetal death Previous fetal growth restriction Maternal perception of reduced fetal movements Vaginal bleeding Abdominal pain	A variety of pathologies result in fetal death, fetal growth restriction, reduced movements, vaginal bleed and abdominal pain. Unless the cause is known the normal approach initially is to assume it is UPVD	Fetal surveillance as in women at risk of UPVD (see above) In women with reduced FM, ongoing surveillance is only needed where the FM do not return to normal In women with vaginal bleeding or abdominal pain ongoing surveillance is needed only where the symptoms persist
Non-specific	Abnormal uterine size and/or growth (larger or smaller than normal)	Many cases of clinically suspected abnormal fetal growth are not confirmed with US. If confirmed, a variety of pathologies result in fetal growth restriction. Unless cause is known the normal approach is to assume it is UPVD	If abnormal fetal size/growth confirmed with US, fetal assessment as in women at risk of UPVD (see above)

Surveillance of fetal health in at-risk pregnancies

On the basis of the clinical risk assessment screening (above) an individualized programme of fetal surveillance will be offered to ‘at risk’ women during their pregnancy. The most commonly used methods are discussed here.

Doppler recordings of blood flow in the umbilical artery (UA)

This investigation has been shown to significantly improve fetal outcome in high-risk pregnancies. Figure 10.10A shows a normal recording.

Fig. 10.10 Doppler ultrasound recording of umbilical artery blood flow. (A) Normal. Note: the left US image shows the UA with red and blue colours indicating blood flow. The right US image is the Doppler recording taken from that UA. The peak of the wave represents the peak of the systolic phase and the trough the diastolic phase of the fetal cardiac cycle respectively. In the normal fetoplacental circulation there is always forward flow even when the heart is not contracting because there is a low resistance to flow within the placental circulation. (B) Abnormal – absent end diastolic flow. Note: there is no forward flow during diastoly for most of the cardiac cycles. (C) Abnormal – reversed diastolic flow. Note: there is forward flow of blood in the UA during systoly but the direction of flow reverses in diastoly.

Figure 10.10B shows an example of ‘absent end-diastolic flow’ (AEDV). The commonest explanation is an increase in placental vascular resistance (‘downstream’ from the point of recording), which is typical of umbilical placental vascular disease (UPVD). The prognosis for the fetus with AEDV is worse with growth restriction, hypoxia and death all being commoner. However, the risk is not usually immediate and management options include continued close surveillance with biophysical testing until a viable gestational age is reached or the biophysical testing is abnormal. If this abnormality occurs at 34 weeks or beyond most would offer the woman elective preterm delivery rather than continuing the pregnancy and the possibility of fetal death.

Figure 10.10C shows an example of ‘reversed diastolic flow’. This is an even more ominous feature and is associated with a much higher chance of imminent fetal death. Management will depend on gestational age. If the pregnancy is at 26 weeks or more then elective preterm delivery (with the attendant risks of prematurity) compared with continuing the pregnancy (and the high risk of fetal death) has to be discussed with the parents. If the pregnancy is less than 26 weeks the discussions are more difficult and the parents may opt for no intervention.

Fetal growth

Fetal growth is best documented in pregnancy using serial US measurements of head (HC) and abdominal (AC) circumferences.

Small fetuses

Three patterns of suboptimal fetal growth are recognized. Once the AC is on or below the lowest centile, the fetus is termed ‘small-for-dates’.

Figure 10.11A illustrates a constitutionally small fetus. Genetic factors contribute to this pattern. Typically the mother will be short and/or of Asian ethnicity. If multiparous, her previous baby(ies) may have been small. Whilst this fetus is not at such a high risk of complications as in the pathologically small fetus (see below), those risks are still greater compared to a normally grown fetus.

Fig. 10.11 Fetal growth patterns detected using ultrasound. (A) Constitutionally small fetus. Note: both HC and AC follow the lowest growth trajectories. (B) Asymmetrically small fetus. Note: the HC follows a normal trajectory whilst the AC crosses trajectories and eventually falls outside the normal range. (C) Symmetrically small fetus. Note: both HC and AC fall away from the normal growth trajectories. Such head growth compromise carries a greater likelihood of developmental delay in childhood.

Figure 10.11B and C represent fetal growth patterns that are due to a pathological cause. They represent different points on the spectrum of fetal growth restriction. The asymmetrical type tends to occur later in pregnancy and is more commonly associated with conditions such as UPVD in the last trimester, whereas the symmetrical type tends to represent a pathological insult that operated from an early point in pregnancy, e.g. fetal abnormality, severe early onset pre-eclampsia. Both are associated with a higher risk of fetal death and hypoxia, preterm delivery and placental bleeding.

Big fetuses

In an analogous way to small fetuses, large fetuses can either be:

• Constitutionally large (‘large-for-dates’) with the HC and AC growth trajectories both following the top centile line. Typically the woman would be tall and/or of Afro-Caribbean ethnicity.

• Pathologically large (‘macrosomia’) with the HC growth trajectory following a centile in the normal range but the AC growth trajectory demonstrates accelerated growth upwards across centiles. This pattern of growth is most commonly seen in fetuses of diabetic women.

Amniotic fluid volume (AFV)

The most accurate estimate of AFV is with US. Two methods are used:

• Single deepest pocket (the normal range is 2–8 cm).

• Amniotic fluid index (AFI) which is the sum of the depths of the pools of amniotic fluid in each of the 4 quadrants of the uterus (top right and left and bottom right and left). Figure 10.12 shows the normal range of the AFI during pregnancy.

Causes of reduced and increased amniotic fluid are discussed in Chapter 4.

Biophysical measurements

The behaviour of a fetus is a useful indicator of his/her immediate wellbeing. With most fetal pathologies, these parameters are affected relatively late in the process. The five observations used in practice are:

• Fetal heart rate (FHR): this is recorded with a cardiotocograph (CTG) (as in labour). The maximum recording time is 40 minutes and in that time there should be at least 2 accelerations of the FHR by 15 beats/min or more and lasting for at least 15 seconds. The patterns of heart rate change are similar to those described in labour (see Chapter 11) with the difference that uterine activity is minimal and more emphasis is therefore placed on the interpretation of baseline heart rate. An example of a normal antenatal CTG is shown in Figure 10.13. This shows a baseline variability of more than 5 beats/min with accelerations and no decelerations. Figure 10.14 shows a normal baseline rate but reduced baseline variability.

Fig. 10.13 Normal antenatal cardiotocograph. The recording shows a baseline variability of >5 beats/min and episodes of accelerations.

Fig. 10.14 Antenatal cardiotocograph showing a normal heart rate but reduced baseline variability.

• Fetal movements: there should be at least 3 separate/discreet movements in 40 minutes of fetal observation with US.

• Fetal tone: at least one of these fetal movements should demonstrate a full 90° flexion–extension–flexion cycle.

• Fetal breathing: there should be a sustained 30 second period of regular fetal breathing movements during the 40 minute observation period.

• AFV: there should be at least one vertical pool measuring between 2 and 8 cm.

The use of all five parameters in combination is called ‘the biophysical profile’ or ‘score’ (BPP or BPS). A normal response is for the fetus to exhibit at least 4 of these parameters in a period of up to 40 minutes (they may be seen in a much shorter period). The original BPS was recorded over 30 minutes but that did not take account of the possibility of normal fetal ‘sleep’ which can last up to 40 minutes and during which no movements, accelerations, or breathing may be seen, hence the change to an observation window of 40 minutes.