Fetal Growth and Growth Restriction

Introduction

Fetuses that are unable to meet their inherent growth potential are at substantial risk for perinatal and long-term morbidity and mortality. Delivery, oftentimes preterm with its attendant consequences of prematurity, is the only known treatment for averting in utero injury or stillbirth for these fetuses. Furthermore, the combination of fetal growth restriction (FGR) and preterm delivery has been associated with even worse neonatal and long-term outcomes compared with appropriately grown infants who were born prematurely. This chapter reviews key definitions, a etiologies, screening, diagnosis and clinical management of FGR while highlighting emerging areas of investigation in the field of normal fetal growth and FGR.

Terminology

Fetal growth restriction, also known as intrauterine growth restriction (IUGR), occurs when a fetus is unable to achieve its inherent growth potential secondary to an underlying pathologic process. Antenatally distinguishing between a pathologically growth-restricted fetus and a constitutionally small one, however, is imprecise. In fact, only approximately 30% of fetuses with an estimated fetal weight (EFW) less than the 10th percentile are pathologically growth restricted. On the other hand, there remains an increased risk for adverse outcome in a fetus that measures greater than the 10th percentile but is still not meeting its innate growth trajectory.

For practical purposes, the American Congress of Obstetricians and Gynecologists (ACOG) defines FGR when the sonographic EFW is less than the 10th percentile for gestational age on a standardised population growth curve. Controversy surrounding this term remains, however, as to whether this is the optimal definition when many of these fetuses will be constitutionally small and not pathologically growth restricted. The phrase ‘small for gestational age (SGA)’ has been utilised in a variety of contexts, ranging from interchangeable use with FGR to denoting only neonates whose birth weight is less than the 10th percentile for gestational age. This latter definition of SGA is used by ACOG and is what the term SGA will represent in this chapter. Low birth weight (LBW) is defined by the World Health Organization as a birth weight of less than 2500 g. This definition does not take into account gestational age and thus has less relevance to fetal growth and growth restriction.

Normal Fetal Growth

Most classic growth curves, including the Lubchenco, Brenner and Williams curves, show similar growth trajectories with advancing gestational age. More recent data derived from a large, racially diverse US cohort, however, demonstrate that birth weights of this modern population differ from those that generated the classic Lubchenco curve. For example, the percentage of SGA infants would tend to be underestimated by Lubchenco curves between 32 and 40 weeks’ gestation ( Tables 39.1 and 39.2 ). In contrast, the percentage of large for gestational age (LGA) infants would be overestimated by the Lubchenco population at term (see Tables 39.1 and 39.2 ). These findings have been supported by a meta-analysis including nearly 4 million births from six countries.

Epidemiology

Overall, the incidence of FGR depends upon the definition and population being used. Using the ACOG definition of FGR based upon population growth charts, 10% of fetuses will be diagnosed as growth restricted. There is no specific definition at this time, however, that is able to take into account a fetus’s inherent growth potential. Although there are investigations into individualised (vs population-based) growth standard, none have been shown to improve outcomes to date.

Classification of Fetal Growth Restriction

Fetal growth restriction has often been segregated into two separate classifications: Symmetric versus asymmetric FGR. Symmetric FGR, in which there is a proportional reduction in all of the biometric parameters, traditionally has been attributed to insults that occur early in pregnancy when the main component of fetal growth is cellular hyperplasia. In contrast, asymmetric FGR, in which estimated fetal weight is below normal primarily because of a decrease in abdominal circumference (with normal skeletal and cranial dimensions), has conventionally been ascribed to placental disorders, which is thought to impair the normal process of cellular hypertrophy in fetal growth and deposition of glycogen in the fetal liver.

The clinical utility of this stratification is unclear for several reasons. For instance, early-onset placental disease may lead to symmetric FGR. More important, though, both symmetric and asymmetric FGR have been associated with increased risk for poor perinatal outcome, and antenatal surveillance and Doppler velocimetry appear to be better predictors of pregnancy outcome regardless of the classification of FGR.

Causes of Fetal Growth Restriction

There are several potential causes of FGR, and they can be divided into three basic categories: maternal, placental and fetal factors ( Table 39.3 ).

Consequences of Fetal Growth Restriction

The consequences of FGR are extensive, traversing the antenatal period to adulthood. In general, FGR increases risks of perinatal morbidity and mortality, with a substantial increase in both as birth weight falls below the 6th percentile for gestational age. Although pregnancies complicated by FGR often undergo indicated preterm delivery, the attendant consequences of prematurity such as respiratory distress (RDS), intraventricular haemorrhage (IVH) and necrotising enterocolitis (NEC) are significantly worse in FGR neonates than gestational age-matched, appropriately grown control participants. Furthermore, neonates who were growth restricted with absent or reversed end-diastolic velocity of the umbilical artery are at even higher risk for adverse outcome. Other potential neonatal complications of FGR include low Apgar scores, hypothermia, hypoglycaemia, hypocalcaemia, polycythaemia and impaired immune function.

Beyond the neonatal consequences, children who were growth restricted at birth also demonstrate higher incidences of chronic medical issues such as bronchopulmonary dysplasia (BPD), pulmonary hypertension, neurodevelopmental delay and cerebral palsy. As adults, these individuals are at increased risk for cardiovascular disease, metabolic syndrome and obesity.

Screening