This chapter should be cited as follows:
Policiano C, Clode N, et al, Glob. libr. women's med.,
ISSN: 1756-2228; DOI 10.3843/GLOWM.411393
The Continuous Textbook of Women’s Medicine Series – Obstetrics Module
Volume 5
Surveillance of fetal well-being
Volume Editor: Professor Diogo Ayres-de-Campos, University of Lisbon, Portugal
Chapter
Sonographic Assessment of Fetal Growth
First published: February 2021
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INTRODUCTION
Fetal size and growth trajectories are important indicators of underlying fetal health. Growth anomalies have long been diagnosed after birth, by weighing the newborn and using terminologies such as low birth weight, macrosomia, small-for-gestational age (SGA) and large-for-gestational age (LGA).1 Both extremes of fetal growth are associated with adverse perinatal outcomes. Fetal growth-restriction (FGR) is the second most common finding associated with stillbirth,2,3 and undiagnosed late FGR constitutes a significant proportion of term stillbirths.4,5 Furthermore, undiagnosed FGR is associated with a higher risk of adverse neonatal outcomes (5-minute Apgar score <4, neonatal seizures, acidosis and neonatal death), when compared to FGR diagnosed during pregnancy.4,5
Fetal macrosomia is also associated with an increased risk of maternal complications such as arrested labor, instrumental vaginal delivery, cesarean delivery, postpartum hemorrhage, genital tract lacerations, as well as neonatal complications that include shoulder dystocia, birth trauma, fetal hypoxia and admission to the neonatal intensive care unit.6,7
For all these reasons, antenatal screening and diagnosis of fetal growth abnormalities is an important part of modern-day obstetrics. The most commonly used screening tool in low-risk populations is serial measurement of fundal height, the distance between the upper border of the pubic symphysis and the uterine fundus. This method has a low sensitivity for the diagnosis of FGR and macrosomia, but a high specificity for the latter, particularly when defined as birth weight above 4500 g.8,9,10 There is still much scientific uncertainty surrounding the benefit of third-trimester sonographic screening of FGR in low-risk pregnancies, as well as on the ideal time to perform it.11 Despite this, it is routinely used in many countries during the early third trimester, a strategy that has recently been endorsed by the World Health Organization (WHO).12
SONOGRAPHIC ASSESSMENT
Whichever method is used for screening, fetal ultrasound has achieved a central role in modern-day diagnosis and management of fetal growth deviations. The most commonly used sonographic definition of SGA is an estimated fetal weight (EFW) below the 10th centile, and the definition of LGA is an EFW above the 90th centile for gestational age.13 The rationale behind using 10th and 90th centile cut-offs for weight-for-age distribution is similar to that of statistical inference using a p-value cut-off of 0.05 for rejecting the null hypothesis. It is also analogous to the concept of mean weight ± standard deviations as cut-offs for abnormal weight-for-age.1,14 Although 10% of normal fetuses will fall below the 10th centile (false positives), the probability that a fetus who is not achieving its growth potential (i.e. has growth restriction) is in this category is much higher, and the magnitude of probability is related to the severity of the disease process.1,15 An important feature underlying this concept is the establishment of growth charts using only “normal” fetuses. Another important understanding is that accurate knowledge of gestational age is essential for fetal growth assessment. For ultrasound dating of pregnancy, evidence is consistent in supporting the measurement of first-trimester crown–rump length (CRL) as the ideal method.16,17,18
SONOGRAPHIC PARAMETERS
A variety of sonographic parameters may be used to diagnose fetal growth abnormalities. Abdominal circumference is considered to be the most sensitive isolated parameter in prediction of SGA,19 especially in low-risk pregnancies and term fetuses, and has a good correlation with FGR and with morbidity parameters, such as hypoxia and acidemia.20,21 However, estimated fetal weight (EFW), using formulas that include head circumference, abdominal circumference, and femur length (FL) is considered the most accurate biometric parameter, in spite of a random error that can reach 14% (close to 400 g in an average term fetus). Errors appear to be higher for small and large fetuses.22
The majority of charts for sonographic EFW are designed to identify fetal growth abnormalities that occur during the third trimester.23,24 Second trimester fetal growth is usually assessed by longitudinal evaluations of the biparietal diameter.22
FETAL GROWTH CURVES
Accurate ultrasound and birth weight standards are essential for the detection of abnormal fetal growth, and the choice of standard has the potential of affecting the percentage of fetuses identified as SGA or LGA.
Birth weight standards before term are often not fully representative of normality, because a great proportion of preterm newborns are also growth restricted, and the prenatal diagnosis was missed. A major area of debate is whether a single universal growth reference chart should be used, or whether parental, ethnic and regional differences in fetal growth are best represented by customizing growth curves to individual characteristics.
“Intergrowth 21” is the name of a research project based at the University of Oxford, which produced a single and universally applicable growth standard, derived from a multi-ethnic population of eight countries.23 The underlying concept is that potential growth is similar in human beings, and that differences observed across countries and populations are mainly explained by variations in nutritional and health status.25 The standards therefore represent how all fetuses should grow under optimal conditions. To construct the reference curves, all pregnancy complications, congenital anomalies and stillbirths were excluded, and a novel formula was used to calculate EFW, based only on head circumference and abdominal circumference. Measurements were not revealed to the ultrasound operator, with the objective of avoiding corrections if extreme values were detected.24
Similar assumptions were taken to construct the WHO fetal growth standards, including data collected from ten countries.25 However, EFW was calculated using Hadlock’s 1985 formula.26 Due to the methodological differences in these studies, their 10th and 90th centiles vary substantially. For instance, at 28, 32 and 36 weeks, the 10th centile of Intergrowth 21 are 75, 164, and 208 g lower than those of the WHO, and the same tendency occurs with the 90th centile. Curiously, the WHO study concluded that maternal characteristics such as height, weight and parity contribute to the differences in growth patterns observed between countries.
A different approach is proposed by Gardosi et al.,27 known as customized Gestation-Related Optimal Weight (GROW) charts (www.gestation.net, Birmingham, United Kingdom). These charts take into account maternal weight, height, ethnicity and parity, as well as fetal sex. Online software is used to calculate gestational age-related EFW curves that are individually customized.28,29 The model has been applied to several different datasets, allowing adaptations to the ethnic and nutritional characteristics of more than 25 countries.
A common criticism of customized growth charts is that nutritional status varies inside a country, namely between rural and urban areas, and that societies evolve due to changes in lifestyle and environment, as well as migratory fluxes. Anthropometric characteristics of the population will therefore evolve over time. The need to update reference ranges at regular intervals has been defended,30,31 but some argue that it is not feasible. A major argument in favor of customized growth curves is that it allows the identification of SGA fetuses in obese mothers that were previously unrecognized when using population-based curves. It also avoids the exaggerated detection of SGA fetuses in thin and nulliparous women, thus avoiding unnecessary investigations and interventions.32,33
Use of customized growth charts is recommended by some scientific societies,34 but a recent systematic review failed to show benefit over population-based charts in identification of SGA neonates at risk for adverse outcomes.35 Indeed it is difficult to show that growth curves improve the identification of pregnancies at increased risk of neonatal morbidity and mortality36,37,38 or adverse neurodevelopmental outcome.39
Currently, two approaches seem reasonable for ultrasound identification of SGA and LGA fetuses: use of customized growth curves adapted to the local population; use of population-based growth curves where the distribution of local population characteristics has been identified. For the latter, it is essential to understand that the definition of LGA and SGA fetuses may not coincide with the 10th and 90th centiles.
ASSESSMENT OF FETAL GROWTH VELOCITY
A single measurement of EFW can only indicate current size. Longitudinal evaluation is necessary to evaluate fetal growth, and to define a growth trajectory. Detection of an abnormal growth trajectory seems intuitively to be a better evaluator of a fetus failing to achieve its growth potential, the concept behind the definition of FGR. Both population-based and customized growth curves have been assumed to represent expected trajectories of normally growing fetuses.40,41 Customization based on the initial EFWs has also been proposed,42 generating trajectories that represent individualized boundaries for a normally growing fetus.43 Fetal growth velocity can be evaluated by changes in EFW or in specific biometric indexes (abdominal circumference or biparietal diameter).44,45 The earlier the first examination is performed, the less likely it is to be biased by factors that impair fetal growth.46
Evidence has suggested that abnormal abdominal circumference growth velocity is associated with perinatal morbidity, in both SGA and LGA fetuses.40,47 In SGA fetuses, those with abdominal circumference growth velocity in the lowest decile were at increased risk for neonatal morbidity (risk ratio [RR] 3.9; 95% confidence interval [CI] 1.9–8.1) compared with those showing normal abdominal circumference growth velocity.48 Similarly, LGA fetuses with increased abdominal circumference growth velocity had a higher risk of neonatal morbidity (RR, 2.0; 95% CI, 1.1–3.6).40
A potential limitation of the growth velocity approach is the statistical phenomenon called regression to the mean, which implies that any variable with an extreme value in its first measurement will tend to be closer to the mean when evaluated repeatedly. Curiously, in low-risk pregnancies, longitudinal assessment of fetal growth during the second and third trimesters has a lower predictive capacity for identifying SGA and late FGR than cross-sectional growth evaluation.49 In contrast, for high-risk pregnancies, a better prediction of adverse perinatal outcomes was achieved with serial ultrasound measurements.50,51 Because of these conflicting results52 and issues related to the cost of this approach, there is insufficient evidence to recommend its wide clinical use, and one-time measurements remain standard practice.
Further studies are required to optimize the performance of serial measurement strategies, particularly to determine the optimal timing and interval between exams.
FETAL BODY PROPORTIONS
Analysis of fetal body proportions is used to classify fetal growth as symmetric or asymmetric, in an attempt to distinguish between the different causes of FGR. When there is placental insufficiency, the brain-sparing effect causes abdominal circumference to be the first biometric index affected by nutritional deficiency. Fetal body proportion models use ratios between abdominal circumference and biometric indexes that are less affected by placental insufficiency, such as head circumference or femur length. The concepts of symmetric and asymmetric fetal growth were widely disseminated in past decades, namely as an aid to determine the etiology of FGR, but similarly to serial measurement strategies, there are conflicting results regarding their capacity to predict adverse perinatal outcomes.53,54
ADDITIONAL SONOGRAPHIC PARAMETERS
The biometric definition of SGA includes two different groups of fetuses: one that is in fact not achieving its genetic growth potential (true FGR) and another that is constitutionally small when compared with the reference population. Recent data suggest that additional ultrasound parameters help to distinguish these two groups and to guide subsequent management. Decreasing the cut-off value of EFW to <3rd centile reduces the number of constitutionally SGA fetuses and selects a higher-risk population, associated with the worst neonatal outcomes.55 Furthermore, the inclusion of functional data from umbilical, uterine, and middle cerebral artery Doppler flowmetry contributes to the identification of true FGR fetuses.56,57,58
Umbilical artery Doppler primarily reflects early-onset placental insufficiency, and most experts agree that EFW <10th centile and abnormal umbilical artery Doppler provide the best criteria to identify early-onset FGR (diagnosis before 32 weeks).59 However, umbilical artery Doppler does not reliably reflect placental insufficiency or predict adverse outcome in FGR detected beyond 32 weeks.60 Middle cerebral artery Doppler seems to be more valuable in the identification of late-onset FGR, as it has a stronger association with adverse perinatal and neurological outcomes.61
Cerebroplacental ratio, combining middle cerebral artery and umbilical artery pulsatility indexes, is an independent predictor of perinatal mortality, and seems to be more sensitive in detection of hypoxia than its individual components. Studies have shown that even in appropriately grown fetuses, an abnormal cerebroplacental ratio is associated with a higher incidence of adverse perinatal outcomes.62 The rationale behind this may be that these fetuses have a higher genetic growth potential and abnormal cerebroplacental ratio reflects a deceleration in fetal growth.
Uterine artery flowmetry reflects adequate trophoblastic invasion, an important step to guarantee adequate nutrient supply and gas exchange for the fetus. Although there is a positive association between abnormal uterine artery flow patterns and adverse outcomes such as pre-eclampsia and FGR, the predictive value of an isolated abnormal test is low, especially for late-onset FGR.59,63,64,65
Venous Doppler velocimetry does not have a role in the diagnosis of fetal growth anomalies, since changes appear late in the evolution of the disease. However, these measurements are useful for serial monitoring of fetal circulation, particularly in severe early-onset FGR.66,67
Oligohydramnios is frequently seen in FGR, following redistribution of blood flow to vital organs at the expense of others, such as the kidney. This parameter can be evaluated by measuring the amniotic fluid index or the single deepest vertical pocket. A randomized controlled trial comparing both methodologies found that amniotic fluid index was associated with more frequent diagnoses of oligohydramnios and increased rates of labor induction, without improving perinatal outcomes. Single deepest vertical pocket may therefore be more valuable, particularly in the low-risk population.68,69 Nonetheless, there is limited evidence to support its use in screening of FGR, or as a predictor of adverse outcome. Polyhydramnios is strongly associated with the diagnosis of LGA.70
A sequential approach to identify and manage FGR is widely used in high-resource settings,71 where EFW is followed by Doppler evaluations to help differentiate between constitutional SGAs and pathological fetal growth anomalies, and also to guide management and timing of interventions.
PRACTICE RECOMMENDATIONS
- Ultrasound remains the mainstay of diagnosis in fetal growth anomalies.
- Estimated fetal weight is the most widely used parameter to detect abnormal growth.
- There is currently no consensus on which fetal growth charts should be used to predict adverse outcome associated with abnormal fetal growth
- To detect small- and large-for-gestational age fetuses, customized growth curves adapted to the local population may be used, or population-based growth curves where the distribution of local population characteristics has been identified, and may not coincide with the 10th and 90th centiles.
- There are insufficient data to recommend the routine use of serial fetal growth evaluations as predictors of adverse perinatal outcomes
- Doppler parameters (umbilical artery, uterine artery, middle cerebral artery and cerebroplacental index) help to distinguish between SGA and true FGR, and guide management and timing of interventions.
CONFLICTS OF INTEREST
The author(s) of this chapter declare that they have no interests that conflict with the contents of the chapter.
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STUDY ASSESSMENT
Question 1
Which of the following statements best applies to sonographic assessment of fetal growth: Single Best Answer (taxonomy 'comprehension')
| (a) | Most fetal growth abnormalities are diagnosed during the second trimester ultrasound by calculating estimated fetal weight | |
| (b) | Fetal head circumference is considered more sensitive and predictive of SGA than measurement of other single parameters | |
| (c) | Amniotic fluid index is the most evidence-based method to evaluate fetal prognosis | |
| (d) | Both customized and population-based growth charts can identify SGA fetuses at risk of adverse outcomes | |
| (e) | Umbilical artery anomalies are strongly associated with late-onset placental insufficiency |
Question 2
Regarding sonographic assessment of fetal growth: True/False Multiple Choice (taxonomy 'comprehension')
| (a) | There is strong evidence that evaluation of the cerebroplacental index is useful in screening for fetal growth restriction | |
| (b) | Estimated fetal weight is the most widely used parameter to evaluate fetal growth | |
| (c) | Population growth charts account for maternal and ethnic characteristics | |
| (d) | Growth velocity evaluation is the most effective and feasible strategy to detect fetal growth anomalies | |
| (e) | Fetal Doppler parameters diagnose fetal growth anomalies |