Javier Caradeux, Eduard Gratacós, and Francesc Figueras
Fetal growth as an indicator of health
During gestation, multiple maternal, fetal, and placental factors interact to determine adequate fetal growth (1,2). Nonetheless, in a considerable proportion of pregnancies, fetal growth will be above or below the expected for gestational age (GA) (3,4). Both conditions have been related to an increased risk of perinatal morbidity and mortality (2,5–7) and long-term health consequences (8–10).
Actually, there are no universally accepted criteria for the diagnosis of abnormal fetal growth (1,11). Commonly used definitions are based on the discrepancy between actual and expected biometric ultrasound measurements for a given GA using arbitrary threshold percentiles (1), labeling fetuses as “small for gestational age” (SGA) or “large for gestational age” (LGA), resembling the diagnosis of malnutrition in children (12,13). However, this approach misclassifies a large proportion of fetuses as it does not distinguish between those fetuses that are constitutionally large or small from those with a pathologic growth pattern. Moreover, there is not a single cut-off that acts as an absolute distinguisher between high and low risk for adverse perinatal outcome (2).
Nonetheless, despite its methodological limitations, dichotomization of fetal weight has proved useful to define groups at higher risk, and it is the current standard in prenatal care in most clinical scenarios. Yet, there is a trend to accept that future gold-standard definitions of abnormal fetal growth should incorporate other functional parameters, such as fetal Doppler or growth velocity (14).
Smallness for gestational age and fetal growth restriction
In about 8%–10% of pregnancies, fetal growth is below expected, that is, less than the 10th percentile for gestational age (4). Small fetuses and newborns have poorer perinatal outcome, including a higher risk of intrauterine fetal death. However, SGA represents a heterogeneous population that comprises several phenotypes. Most of these cases correspond to “constitutional” healthy fetuses that merely represent the end of the spectrum of healthy babies. Yet, a fraction of them presents a pathologic growth pattern also known as fetal growth restriction (FGR). This condition is associated with deficient placental function, worse perinatal outcome, and higher rates of long-term cardiovascular and metabolic diseases (15–17).
FGR presents as two phenotypes. Figure 4.1 and Table 4.1 depict the main characteristics of both forms. Early FGR (detected <32 weeks) is strongly related to placental insufficiency and linked with most of morbidity and mortality. Late FGR (detected >32 weeks) is characterized by a milder and near term presentation (18). Early diagnosis and classification define management and prognosis (18,19). Indeed, nondetection of FGR confers an increased risk of adverse perinatal outcome (20) and stillbirth (21).
Figure 4.1 Prevalence changes across pregnancy of early and late fetal growth restriction.
Table 4.1 Differential features of early and late fetal growth restriction (FGR)
Management (gestational age at delivery)
Detection and diagnosis
High mortality and morbidity
Low mortality/morbidity + high prevalence = large etiological % of the adverse outcomes
Evidence of placental disease
70% abnormal umbilical Doppler
60% association with preeclampsia
Severe angiogenic disbalance
<10% abnormal umbilical Doppler
15% association with preeclampsia
Mild angiogenic disbalance
Systemic cardiovascular adaptation
Central cardiovascular adaptation
Low cardiac output
High vascular resistance
High cardiac output
Normal/reduced vascular resistance
While conceptually FGR and SGA are clearly distinct conditions, from a clinical point of view their differentiation is rather challenging. Therefore, fetal size is usually used as a proxy, and a SGA fetus has been regarded as an equivalent of FGR.
Detecting SGA in advance of delivery has several potential benefits. It prompts further investigations, such as umbilical artery Doppler study, which has been shown to reduce stillbirth and increase preterm delivery without increasing neonatal mortality (22). It also alerts clinician and mother about the increased risk involved, enabling deliberations on the optimal timing of delivery.
Largeness for gestational age and macrosomia
Fetal macrosomia, commonly defined as birth weight >4000 g (1,23), is also present in more than 10% of gestations (3), and it is associated with several delivery complications including birth trauma, shoulder dystocia, and perinatal asphyxia (3,24). Since a clear weight cut-off definition has not yet been established, a value independent of gestational age, such as LGA, has been proposed to define a birth weight associated with increased complications (3,25,26). However, both groups barely overlap, as LGA threshold falls far below the 4000 g depending on the gestational age selected. While this could lead to an increase in sensitivity, it also could be associated with a lower specificity and an increase in false-positive rates. Figure 4.2 illustrates the concept of macrosomia and LGA.
Figure 4.2 Macrosomia and largeness for gestational age.
Regarding management, once fetal macrosomia is suspected, an elective cesarean section can be done to avoid complications related to vaginal delivery. However, the number of interventions needed to prevent one complication makes this approach clinically and economically unsound (27). Recently, induction of labor for impending macrosomia has been proposed to prevent complications, without increasing the cesarean section and instrumental delivery rates (23). This has put the spotlight on improving prediction of excessive fetal weight or macrosomia before labor onset for proper counseling and decision-making.
Fetal growth: A dynamic process
Fetal growth is a complex and dynamic process that is heavily modulated by placental function, with the placenta serving the critical respiratory, hepatic, and renal functions of the fetus (1). As gestation advances, the capacity of the uteroplacental system to meet fetal demands gradually declines (28); in early stages, this dysfunction could not be enough to be reflected by Doppler parameters (29,30). However, mainly near term, it could be enough to compromise fetal growth and well-being (2,31) without reaching the predefined threshold to be classified as SGA.
On the other side, maternal nutritional and metabolic status has also been shown to have direct influences in placental function and pregnancy outcome (32). Higher rates of macrosomia and adverse perinatal outcomes have been described in obese patients (33). However, a clear understanding of the pathways and interactions involved in fetal overgrowth has not been reached; some factors such as maternal hyperglycemia have been shown to increase the risk of LGA in a linear relationship (34).
It has been argued that a cross-sectional assessment of estimated fetal weight would be unable to capture the behavior of the fetal-maternal dynamic, rendering a poor performance to current screening strategies. It has been proposed to incorporate the estimation of fetal growth velocity in prenatal care as this would better reflect the evolution of this relation (19,35,36). Yet, if growth velocity adds additional information over knowing fetal size alone, it is still a matter of research (37–40).
Current screening strategies
Despite its methodological limitations, most screening strategies rely on cross-sectional evaluation of fetal size (usually abdominal circumference [AC] or estimated fetal weight [EFW]) at one point during the third trimester. Nonetheless, despite implementation of multiple strategies and wide availability of ultrasound, detection rates remain low.
Regarding detection of late-SGA, systematic review and meta-analysis have been published recently (41), including a total of 21 series on routine ultrasound screening performed at a mean gestational age >32 weeks and a total of 6,835 SGA babies. Reported modeled sensitivities of AC and EFW <