The term FGR was created for fetuses with predicted weight below the 10th percentile for a given gestational age. The original standards for fetal growth were based on work carried out by Lubchenco et al. in Denver [1]. Subsequent studies undertaken in differing populations have produced newer adjusted growth curves. In contrast to FGR, which refers to abnormal growth, small for gestational age (SGA) is a quantitative description of infants with birthweights below the 10th percentile, including those who are constitutionally small. Since fetuses that are SGA are not necessarily growth restricted, a more exact definition of FGR is a fetus that fails to reach its growth potential, and is therefore at risk for adverse perinatal morbidity and/or mortality.

Fetal growth restriction is a syndrome with various etiologies. The risk factors for FGR can be separated into fetal, placental, and maternal origins. Growth restriction is classified as symmetric or asymmetric (“head sparing”). Early fetal insult or intrinsic abnormalities resulting in a reduction in fetal cell number produce symmetric growth restriction. Asymmetric growth restriction is thought to result from an inadequate transfer of nutrients and oxygen to the fetus, which evolves over the course of the pregnancy. Therefore, asymmetric FGR manifests later in gestation. “Head sparing” develops when the fetus responds to a limited nutritional source by selectively supporting the brain and vital organs as well as minimizing growth and activity to reduce metabolic demands.

Fetal

Intrauterine infection has long been associated with FGR. Although it probably accounts for less than 10% of all cases, infectious agents can produce disruption of cell growth, potentially resulting in significant residual deficits. The children have a higher incidence of mental deficiencies and are less likely to have normal growth in childhood. Herpes, cytomegalovirus, rubella, and toxoplasmosis have all been demonstrated to produce growth restriction. Similarly, many chromosomal abnormalities such as trisomies 13, 18 and 21 and malformation syndromes result in a reduced cell number which leads to early onset of growth impairment.

A more common cause of FGR is multifetal gestation. Approximately 20% of these pregnancies are complicated by impaired growth of one or more fetuses. The most common reasons for FGR in these cases are the relative decrease in placental mass, abnormal placentation, and placental vascular anastomoses. In twin pregnancies, fetal growth begins to decrease, relative to singletons, at approximately 32 weeks, and FGR is the second most likely cause of morbidity after prematurity.

Placental

Decreases in the functional mass of the placenta can compromise fetal growth by limiting the transfer of necessary nutrients. Growth restriction has also been described in pregnancies in which there is placental mosaicism, meaning the placenta is made up of both normal and aneuploid cell lines. Abnormal placentations such as circumvallate placenta, partial placental abruption or infarction, placenta previa or placenta accreta can result in FGR. Hemangiomas or other placental tumors can also shunt substrate away from the fetus and restrict growth. Other umbilical–vascular abnormalities associated with FGR include single umbilical artery and velamentous cord insertion. Studies have found that women with an unexplained elevation in maternal serum α-fetoprotein or human chorionic gonadotropin in the second trimester have an increased risk of having a fetus with FGR. This may be explained by abnormal placentation.

Maternal

Poor nutrition and poor weight gain have both been associated with FGR. While the severity of nutritional restriction necessary to produce reduction in fetal size is unclear, pregnant women living in famine conditions produce smaller infants. However, women with limited gastrointestinal absorption secondary to diseases such as ulcerative colitis or Crohn’s disease have not been reported to have a significantly greater risk of FGR. Even patients who have undergone ileojejunal bypass for weight control produce infants which, although smaller than average, do not fall below the 10th percentile.

Maternal ingestion of teratogenic medications can also adversely affect fetal growth. Both therapeutic medication (anticonvulsants, coumarin) and illicit drugs (narcotics, cocaine) have been associated with poor fetal weight gain.

Alcohol has a linear dose-related association with impaired fetal growth, and up to 30% of fetuses of heavy drinkers (five or more drinks per day) will display features of fetal alcohol syndrome. Tobacco has long been documented to impair fetal growth. This may be due to chronic fetal hypoxia, since the decrement in fetal size is directly proportional to the number of cigarettes smoked. Nicotine alone is not associated with FGR.

Maternal vascular diseases, such as those found with chronic hypertension, diabetes or collagen vascular disorders (systemic lupus erythematosus, antiphospholipid antibody syndrome), all predispose to FGR. Vascular disease reduces uteroplacental blood flow and transfer of nutrients to the fetus. Pre-eclampsia is associated with abnormal trophoblastic invasion of maternal spiral arterioles, which ultimately results in luminal narrowing and diminished placental blood flow. Sickle cell disease is also associated with FGR, because of local hypoxia secondary to poor uterine perfusion rather than maternal hypoxemia.

Finally, conditions in which there is chronic maternal hypoxia (cyanotic heart disease, pulmonary disease, and high altitude) or maternal anemia reducing oxygen transfer to the fetus are risk factors for compromised fetal growth.

Identification of patients at high risk of developing IUGR begins with a thorough history. Social history, dietary habits, use of medication, as well as history of infectious symptomatology during the pregnancy, are important. Elucidation of the previous obstetric history, with particular reference to birthweights, gestational ages, and neonatal development, is also essential as the history of a previous infant with FGR is the strongest predictor for delivery of an affected infant.