Intrauterine Growth Restriction

Summary

Intrauterine growth restriction (IUGR) broadly encompasses pregnancies complicated by poor fetal growth, where the fetus's growth is less than its genetic potential. IUGR is an important condition to recognize, as it is a common complication of pregnancy that has both short- and long-term sequelae for offspring. This is a particularly difficult diagnosis to manage in both the prenatal and postnatal periods for a number of reasons. Firstly, definitions and terminology lack consensus among practitioners, researchers, as well as organizations that inform clinical practice. Secondly, the etiologies are multiple, and the pathophysiology remains incompletely understood. Given these challenges, diagnostic criteria and prenatal practice guidelines remain uncertain, no definitive prevention strategy or treatment has been identified, and postnatal management and surveillance guidelines are scant, variable, and ill defined. Despite the major global burden of IUGR, it remains a condition that is difficult to diagnose, prevent, or treat, and further research is essential in this field.

Definitions and Terminology

In clinical practice and in research studies, IUGR can be defined in multiple ways and there remains a lack of consensus regarding terminology. Commonly, “normal” fetal growth results in a neonate whose birth weight falls between the 10th and 90th percentile for gestational age (deemed “appropriate for gestational age” or AGA). Therefore, a birth weight less than the 10th percentile is categorized as “small for gestational age” (SGA) and correlates with a birth weight that is two standard deviations or more below population norms. In contrast, IUGR encompasses all fetuses with evidence of malnutrition or in utero growth restriction, which can still include an infant born with a birth weight above the 10th percentile. Therefore, close communication between the obstetric and newborn medical teams is imperative to accurately identify which neonates exhibited true in utero growth deceleration and not base the label of “IUGR” on birth weight alone. Clinically, this is an essential distinction to make as infants with IUGR are at risk for both short-term and long-term complications, whereas constitutionally small infants that fall into the SGA category but had consistent growth patterns in utero are at much lower risk for long-term adverse outcomes.

The Health Burden of IUGR

Given the difficulties and inconsistencies in defining IUGR, the true prevalence of IUGR is not known. However, it has been estimated that up to 10 percent of live-born infants are characterized as IUGR, and that this percentage is likely higher among stillborn neonates. Globally, IUGR is the second leading cause of perinatal morbidity and mortality after prematurity. The risk of fetal death increases with severity of growth restriction, such that a fetus with a weight less than the 10th percentile for gestational age has a 1.5% risk of fetal death (twice the risk of stillbirth in normally grown fetuses), whereas risk for a fetus with a weight less than the 5th percentile increases to 2.5%.

Not only does fetal growth restriction increase overall mortality by increasing risk of intrauterine demise, stillbirth, and neonatal death, it also carries significant co-morbidities for the surviving neonate. After birth, IUGR neonates are at increased risk for admission to the intensive care unit, requiring monitoring and treatment for complications of IUGR, which include but are not limited to hypoglycemia, hyperbilirubinemia, hypothermia, and respiratory distress syndrome. These issues will be discussed more in the management section of this chapter. In the long term, infants born IUGR are at risk for neurodevelopmental delay and cardiometabolic diseases in adulthood, including obesity, type 2 diabetes mellitus, and cardiovascular disease.

Classification of IUGR

Historically, IUGR has been classified into two types: asymmetric versus symmetric ( Table 15.1 ). In asymmetric IUGR, it is believed that decreased fetal growth occurs in response to suboptimal intrauterine provision of nutrients and oxygen. The fetus adapts to this environment by conserving energy and focusing nutrient delivery to vital organs such as the brain and the heart. Therefore, asymmetric IUGR typically manifests as a fetus with a disproportionately high head circumference percentile compared to percentile for weight. Height can be normal to low normal. Prenatally, fetal growth deceleration in asymmetric IUGR tends to manifest in the third trimester (notably, the period of most rapid fetal growth), when prenatal measurements on growth scans demonstrate a low abdominal circumference, whereas head circumference, biparietal diameter, and femur length often remain within normal ranges. This pattern of growth has also been coined as “head-sparing” IUGR. Asymmetric IUGR is more common than symmetric, accounting for 70%-80% of all IUGR fetuses, and more often than not can be due to maternal, environmental, and/or placental factors that result in placental insufficiency.

Symmetric IUGR, on the other hand, results in a fetus or neonate with proportionately low anthropometric measurements of head circumference, weight, and length. This pattern is less common than asymmetric IUGR, representing 20%-30% of all IUGR cases, and the poor growth rate is often detectable earlier in pregnancy. Often, asymmetric IUGR is seen in association with fetal etiologies such as genetic or chromosomal disorders, and prognosis is generally worse in these cases. It can also be seen with early pregnancy infections resulting in congenital syndromes, such as congenital rubella or congenital cytomegalovirus (i.e., “TORCH” infections). At times, severe maternal malnutrition extending from the first trimester throughout pregnancy can result in symmetrical IUGR, which is also seen with maternal malarial infection.

Etiology of IUGR

There are four broad etiologic categories for IUGR: maternal, fetal, placental, and environmental factors. IUGR can also result from a combination of these factors, as inherent genetic potential and the “environment” both determine fetal growth ( Fig. 15.1 ). Although the underlying pathophysiologic mechanisms may differ among and within these categories, the majority of IUGR cases share the same common pathway that results in suboptimal nutrient and oxygen provision to the fetus, oftentimes secondary to poor placental perfusion ( Table 15.2 ). The exception to this common pathway is oftentimes due to “fetal” etiologies, which largely are due to genetic or structural disorders and thought to result from a decreased number and growth of fetal cells.