Symphysis–fundal height

Routinely, symphysis–fundal height (SFH), the distance from the symphysis pubis to the uterine fundus, is measured at each midwife or antenatal attendance from 24 weeks’ gestation. As a guide, the SFH in centimetres is equal to the number of weeks of gestation plus or minus 2 cm. After 36 weeks, the acceptable difference increases to 3 cm. However, SFH has poor intra‐ and inter‐observer reproducibility. SFH is also prone to error due to factors unrelated to fetal biometry, such as maternal obesity, fibroids, polyhydramnios and fetal lie.

There has been recent interest in standardizing SFH measurement by introducing training packages, and plotting the measurement on SFH charts that are generated at booking and adjusted for maternal characteristics. The validity and usefulness of this approach remains to be proven.

Ultrasound biometry

Ultrasound is the current gold standard for fetal growth assessment. Measurements are made of the head circumference, abdominal circumference and femur length. In some cases, biparietal diameter may also be measured. These measurements are inputted into an algorithm, the most common being that developed by Hadlock, to calculate EFW, particularly the four‐parameter model. This can then be plotted against gestation‐specific centiles.

Customized charts

There remains controversy as to whether fetal growth is the same in all healthy populations, or whether specific differences exist. Two recent studies, INTERGROWTH and WHO, both carried out in different centres throughout the world, have reached different conclusions on this matter. INTERGROWTH suggests that fetal growth is no different in optimally healthy women throughout the world, whereas the WHO study has shown small but significant differences in growth. The controversy is sure to continue, and with it the question of whether customizing birthweight percentiles based on maternal characteristics is appropriate.

Causes

The assessment of the cause of an SGA fetus has important implications for the antenatal management and long‐term prognosis. At initial presentation, accuracy of dating of the pregnancy should be assessed and expected date of delivery confirmed. Gestation should be assigned by crown–rump length between 45 and 84 mm (11⁺² to 13⁺⁶ weeks’ gestation); beyond this gestation, head circumference should be used, although in cases of in vitro fertilization (IVF), embryo transfer dates can be used with a correction for day 2 or 5 transfer.

Evidence of poor placentation, failure of adaptation of the spiral arteries and adaptation of the maternal vasculature can be assessed by increased impedance and/or ‘notching’ in the uterine arteries (Fig. 17.1). Abnormal fetal Doppler indices or oligohydramnios are also suggestive of placental dysfunction as the cause of a small fetus.

A small fetus may have an underlying chromosomal abnormality, particularly when presenting in the second trimester, and invasive testing should be discussed. A detailed anomaly scan should be performed, as any further anomaly would increase this risk further. Serological testing for cytomegalovirus and toxoplasmosis should be performed in severely growth‐restricted fetuses. It should be borne in mind, though, that features of placental dysfunction (see above) may also be seen in a poorly functioning placenta secondary to a chromosomal abnormality or infection.

After exclusion of these causes, it should be considered whether a small fetus is constitutionally small. In such cases surveillance is warranted, although these fetuses will often follow a normal growth trajectory and have a good prognosis.

Prediction

Because of its heterogeneous aetiology, prediction of growth restriction is complex particularly in first pregnancies. At booking, which usually takes place at 10–13 weeks’ gestation, women can be assessed for risk factors. From history alone, these can be subdivided into maternal risk factors, maternal medical conditions and previous pregnancy history (Table 17.2). Paternal SGA should also be noted as this has an odds ratio (OR) of 3.7 for an SGA fetus.

As pregnancy progresses, further risk factors may become evident. In women undergoing combined screening for common trisomies, pregnancy‐associated plasma protein A (PAPP‐A) is routinely measured. PAPP‐A is a placentally derived protease whose main substrate is insulin‐like growth factor binding proteins and its serum levels are related to both the function and size of the placenta. There is an association between low PAPP‐A levels and low birthweight. Multiple other serum markers have been studied. These include those related to placental mass and function (e.g. ADAM‐12, PP‐13, IGFBP‐1 and IGFBP‐3), those related to angiogenesis (e.g. VEGF, endoglin, PGFa and sFlt‐1) and those related to endothelial function (e.g. asymmetrical dimethylarginine and homocysteine). None of these has been found to have predictive value that is of clinical use [9].

Ultrasound parameters have been shown to have some utility. The impedance to flow within the uterine arteries can be readily measured. In healthy pregnancy there is normally low resistance and high flow. Abnormalities of uterine artery Doppler waveform include increased impedance and ‘notching’ (Fig. 17.1). Uterine artery Doppler performed at 24 weeks’ gestation has 80% sensitivity for a 5% screen‐positive rate for the prediction of a fetus that will require delivery prior to 34 weeks due to growth restriction. The predictive value of uterine artery Doppler on its own in the first trimester has low sensitivity.

Various algorithms have been developed for the prediction of fetal growth restriction. These commonly use a combination of maternal history, maternal physiological measurements, serum markers and ultrasound parameters. To date, none has had sufficient sensitivity at an acceptable false‐positive rate to warrant introduction into routine clinical practice.

Umbilical artery Doppler

The umbilical artery Doppler waveform is the primary Doppler assessment in fetuses with growth restriction. Management protocols based on measurement of the umbilical artery waveform in high‐risk pregnancies has been shown to reduce perinatal deaths by up to 29%, though it is not clear on what basis decision‐making is improved.

As placental dysfunction increases, there is increasing impedance in placental vessels. This initially presents as raised umbilical artery impedance, detected by increased values in either the resistance index (RI) or pulsatility index (PI). As the uteroplacental circulation is increasingly impaired, absent EDF in the umbilical artery is noted, indicative of loss of normal function in about 60–70% of villi, with progression to reversed EDF as remaining normal placental function is lost (Fig. 17.2). The progression of changes in umbilical artery Doppler waveforms can be rapid and unpredictable, particularly in early‐onset fetal growth restriction (FGR). Absent or reversed EDF after 26 weeks of gestation has been shown to have an independent impact on neurodevelopment.

A recent Cochrane systematic review and meta‐analysis, including 18 studies and over 10 000 women, demonstrated that women who had Doppler assessment had a significantly lower perinatal mortality (1.2%) compared with those who had not been assessed by Doppler (1.7%; relative risk or RR 0.67; 95% CI 0.46–0.96). Although the data for secondary outcomes showed that there were fewer adverse outcomes in the Doppler group, this did not reach statistical significance [10]. Interestingly, there was a reduction in interventions including induction of labour and lower segment caesarean section in the Doppler group. There was no difference in operative vaginal delivery rates or Apgar scores at 5 min. Notably, though, there is a lack of data on long‐term neurological development in the babies in either group.

Middle cerebral artery Doppler

Unlike umbilical artery Doppler, middle cerebral artery (MCA) Doppler can be a proxy for hypoxia and may be abnormal for many weeks in early‐onset FGR. The role of the cerebral arteries and the changes that occur in the vessels are important in relation to the concept of ‘brain‐sparing’ in the chronically, or indeed acutely, hypoxic fetus. Although now debated, the concept of ‘brain‐sparing’ involves redistribution of blood by dilatation of the cerebral vessels, thus increasing substrate and oxygen supply to the brain, in response to fetal chemoreceptor or baroreceptor stimulation.

The value of MCA Doppler in the prediction of adverse fetal outcome and assessment of the at‐risk fetus has been reported variably. Some studies have suggested that assessment of MCA Doppler is a useful tool, whereas others have found poor predictive value [11–14]. Recently, a meta‐analysis of eligible studies (35 in total) including 4025 fetuses has been performed [15]. This found that low MCA PI appears to be associated with fetal well‐being assessed by acidosis (pH <7.20) at birth (although this finding is largely biased by a single study in a high‐risk population [16]), Apgar score below 7 at 5 min or admission to neonatal intensive care.

It is important to recognize that while these findings do suggest that there is an association between abnormal MCA and adverse outcomes, the association is weak. Overall, this meta‐analysis suggests that in clinical practice MCA alone has limited predictive value for compromise of fetal or neonatal well‐being.

Cerebroplacental ratio

As discussed in the previous section, the normal physiological response of MCA dilatation in fetuses exposed to acute or chronic hypoxic conditions results in a reduction in fetal MCA PI. Commonly, though not universally, this is associated with increasing impedance in the umbilical artery. Whilst the values obtained on measuring these Doppler parameters individually may be within normal limits, it is possible that the fetus is compensating. By using the ratio of MCA to umbilical artery Doppler PI – the cerebroplacental ratio (CPR, also called the cerebro‐umbilical ratio) – it may possible to determine which fetuses may be at risk of compromise, as those with abnormal (i.e. low) CPR may be considered to have failed to reach their growth potential [17,18].

A low CPR [17,19] may be associated with delivery by lower segment caesarean section due to fetal compromise, determined by either abnormal CTG or fetal blood sample below pH 7.20, although no differences in Apgar scores and arterial pH (taken at time of delivery) were found nor is there evidence of adverse neonatal outcomes in the groups with low CPR in either study. However, others [20] have also associated low CPR (PI <1) with adverse perinatal outcome in intrauterine growth restriction (IUGR) and impaired neurodevelopment at 2 years of age.

CPR may be of most use when umbilical artery PI is greater than the 95th centile with a normal waveform, in which situation a low CPR gives an OR for adverse perinatal outcome of 11.7 (95% CI 6.0–22.9). This provides similar predictive value to an abnormal umbilical artery waveform (OR 10.8, 95% CI 3.8–30.5) compared with raised umbilical artery PI alone (OR 6.9, 95% CI 2.9–16.5). It should be remembered that gestation and birthweight remain the most important predictors of morbidity and long‐term outcome.

Ductus venosus Doppler

The ductus venosus (DV) is a fetal vessel connecting the intra‐abdominal portion of the umbilical vein to the left portion of the inferior vena cava just below the diaphragm [21]. The function of the DV is to shunt the oxygen and substrate‐rich blood coming from the placenta via the umbilical vein to the heart. The DV diverts 25% of the blood to the heart, with the remainder being distributed to the liver and joining the circulation via the hepatic portal system. Although entering the heart via the right atrium, this substrate‐ and oxygen‐rich blood is preferentially directed to the left atrium and then, via the left ventricle and aorta, to the fetal heart and brain [22,23].

The utility of the DV waveform is primarily in the very premature fetus with IUGR, or the preterm fetus with abnormal umbilical artery waveforms (Fig. 17.3). Reversal or absence of the DV a‐wave, particularly in combination with umbilical vein pulsations, has been shown to be closely associated with a pH below 7.20 [24] and perinatal mortality irrespective of gestational age, with a risk of up to 100% in early‐onset FGR. It has been shown that DV abnormalities precede changes in computerized CTG in 50% of cases, although it is safe to wait DV PI or waveform changes in cases where computerized CTG remains normal [25].

The TRUFFLE study and the application of its results to the timing of delivery in early‐onset IUGR is discussed later.

Cardiotocogram and biophysical profile

CTG monitoring as an assessment of fetal well‐being has become a routine part of antenatal care. There is, however, no evidence of benefit in high‐risk cases and may in fact result in unnecessary intervention [26].

However, computerized CTG monitoring can provide assessment of short‐term variability (STV), which cannot be performed by visual assessment alone. Reduced STV (<3 ms) has been shown to correlate with the fetal metabolic state and significantly reduced STV is closely associated with fetal acidaemia [27–29]. This has been shown to reduce perinatal mortality compared with traditional CTG in the high‐risk population (RR 0.20, 95% CI 0.04–0.88) [26], although this effect was not evident once deaths due to congenital anomalies were excluded (OR 0.23, 95% CI 0.04–1.29).

As such, CTG monitoring should not be used as the only form of surveillance in SGA fetuses. If CTG monitoring is used, interpretation should be based on analysis of STV on computerized CTG [30].

The biophysical profile combines the use of CTG with the ultrasound assessment of fetal movement, fetal tone, fetal breathing movements and amniotic fluid. Each parameter is scored 0–2 points, with a maximum total score of 10. A normal score (8 or greater) is reassuring. Biophysical profile has a high false‐negative rate and is not a good predictor of fetal acidaemia. It has also been shown to increase caesarean section rates, but not improve perinatal outcome. The use of biophysical profile is not recommended for surveillance of the SGA fetus.