KEY POINTS
• Aberrations of fetal growth increase the risk of fetal and neonatal morbidity and mortality.
• Maternal comorbidities such as obesity, diabetes, hypertension, and other vascular diseases predispose to complications from fetal growth abnormalities. Comprehensive management of these conditions may prevent perinatal complications.
• Women at risk for growth abnormalities should be screened with sonographic evaluation of fetal growth and well-being and other fetal surveillance as appropriate. Delivery management may be dramatically influenced by fetal growth abnormalities.
INTRAUTERINE GROWTH RESTRICTION
Background
Definitions
• The most commonly used definition for intrauterine growth restriction (IUGR) in the United States is an estimated fetal weight less than the 10th percentile (1,2). Fetuses with lagging abdominal circumference are deemed “at risk” and should be followed closely for development of IUGR.
• Estimation of fetal weight is heavily influenced by parental race, fetal gender, genetic influences, maternal body mass index (BMI), and altitude (2,3).
• Many fetuses with estimated weights less than the 10th percentile, or with small abdominal circumferences, are constitutionally small, and it is often challenging to differentiate the growth-restricted fetus from the constitutionally small fetus that is meeting its growth potential.
Etiology and Pathophysiology
• Fetal life is a period characterized by phases of rapid cell proliferation and differentiation (1). IUGR is the result of disruption of this normally proliferative state. IUGR may be symmetrical if the disruption occurs early and globally within the fetus or asymmetrical when the insult occurs later in gestation and preferentially impairs growth of the fetal abdominal circumference. Different etiologic mechanisms lead to varying degrees and patterns of growth restriction.
• Pathologic findings on placental examination are the hallmark for the diagnosis of true IUGR versus a constitutionally small fetus. However, for obvious reasons, this information is not available to the clinician to aid in the management of the pregnancy. Placental abnormalities associated with IUGR include decreased placental weight, decidual necrosis, and infarction. Histologic changes in placental villi including hypermaturity, villus edema, and infarction are characteristic of placental insufficiency and resultant fetal hypoxia. Massive intervillus fibrin deposition, or “maternal floor infarction,” is a lesion of particular importance because it is associated with high rates of severe fetal compromise and stillbirth and tends to be recurrent with future pregnancies (3).
• Maternal, placental, and fetal factors may lead to the development of IUGR. Maternal factors are as follows:
• Medical comorbidities: including chronic hypertension, pregestational diabetes, lupus, cardiovascular disease, thyroid dysfunction, nephrotic syndrome, hemoglobinopathies, antiphospholipid antibody syndrome, severe pulmonary conditions, and severe nutritional deficiencies.
• Medications used to treat comorbidities may increase the risk of IUGR:
Antiepileptics
Warfarin
Folic acid antagonists
Possibly beta-blockers
• High doses of radiation have been shown to cause symmetrical growth restriction.
• Social habits:
Tobacco use
Excessive alcohol intake
• Cocaine/amphetamine exposures and other drug exposures.
• Severe maternal nutrition deficiencies.
In the adequately nourished woman, regardless of weight, minimal weight gain and even weight loss are unlikely to cause IUGR.
Women with severe nutritional deficiencies secondary to poor resources, extremely poor diet, or conditions such as severe hyperemesis gravidarum are at risk for IUGR.
• Obstetrical complications predispose a pregnancy to an increased risk of IUGR.
• Preeclampsia
Both placental vascular changes and a contracted maternal intravascular volume contribute to restriction in fetal growth.
• Multiple gestation
As many as 30% of twin pregnancies may have IUGR in one or both twins. This is especially true in monochorionic twins and specifically in the setting of twin–twin transfusion syndrome (4).
• Recurrent bleeding
• Preterm premature rupture of membranes
• Placental abnormalities that have been associated with an increased risk of IUGR:
• Placenta previa
• Subchorionic hemorrhage
• Partial/chronic abruption
• Aberrant cord insertions
• Fetal factors.
• Fetal karyotype abnormalities, such as trisomy 21, trisomy 18, trisomy 13, and triploidy, commonly have significant IUGR.
• Major fetal malformations are often associated with poor fetal growth.
Abdominal wall defects, skeletal dysplasias, and others interfere with the ability to accurately estimate fetal weight using ultrasound and may not be associated with true growth restriction.
Neural tube defects, heart defects, or fetal tumors may be associated with growth restriction both because of increased demand on the fetal cardiovascular system and because of association as part of a fetal syndrome associated with IUGR.
• Congenital infections are relatively uncommon causes of growth restriction but should be considered especially when other markers for congenital infection are present.
Viral infections such as cytomegalovirus, parvovirus, rubella, and HSV are associated with IUGR.
Protozoan parasites such as Toxoplasma gondii have also been shown to cause IUGR.
Fetal Adaptation
• The fetus with growth restriction secondary to uteroplacental insufficiency with hypoxia adapts to its environment by a variety of mechanisms.
• Fetal metabolism is shifted toward anaerobic metabolism, producing lactic acid and altering the acid–base status of the fetus.
• Compensatory polycythemia to improve oxygen delivery to tissues that when pronounced may paradoxically decrease tissue perfusion.
• Cardiovascular changes that redirect blood flow to vital organs such as the fetal brain, heart, and adrenal glands develop and offer an opportunity to quantitate the degree of fetal impairment.
• Decrease in fetal urine output as blood is shunted from the fetal kidneys, leading to a consequent decreased amniotic fluid volume.
• Ultimately, the fetus adapts to the hypoxic, hypoglycemic environment by conserving energy, and behavioral changes, as measured by the nonstress test and biophysical profile, become evident.
Evaluation
• History
• A detailed history can help to identify patients at risk for IUGR such that more aggressive surveillance is undertaken. In addition, information gained from a detailed history can help direct the diagnostic evaluation when a fetus with IUGR is discovered.
• Physical exam
• The fundal height measurement is considered the primary method of screening for IUGR in the general obstetric population. Although it is nonspecific and poorly sensitive, it remains the most common method for screening for IUGR in low-risk patients (2).
• Assessing maternal weight gain is not a sensitive or specific method for the detection of IUGR.
• When IUGR is identified, a detailed exam for signs of preeclampsia and other medical comorbidities is useful.
• Ultrasound
• Ultrasound is the primary diagnostic tool for the evaluation of IUGR.
Equations that use abdominal circumference, biparietal diameter, and femur length have been shown to be the most accurate at estimating the fetal weight (4,5).
While both first-trimester biometry and second-trimester biometry have been used to predict subsequent small for gestational age (SGA) neonates, second-trimester biometry appears to be superior (6).
Accurate pregnancy dating is a prerequisite to the ability to accurately diagnose IUGR.
Customized growth curves may lower the false-positive rate of biometry for the prediction of true growth restriction, although such curves are variably used (7,8).
• The finding of IUGR on ultrasound should prompt a detailed evaluation of fetal anatomy, quantification of the amniotic fluid volume, and performance of umbilical artery Doppler studies. In appropriately aged fetuses, additional measures of fetal well-being such as a biophysical profile or nonstress test can provide meaningful information regarding the overall status of the fetus.
• In fetuses found to have IUGR who remain undelivered, serial ultrasounds at intervals of at least every 2–4 weeks should be considered. In the specific setting of preeclampsia, more regular measurements of the fetus may be indicated, but it is not generally recommended to repeat biometry at intervals less than 2 weeks given the inherent error range of biometric measurements.
• Laboratory
• When IUGR is diagnosed in the midtrimester, consideration for karyotype analysis should be undertaken, particularly if there are associated fetal malformations. Genetic amniocentesis has traditionally been recommended to evaluate for aneuploidy in high-risk patients. In patients at moderate or low risk who wish to avoid an invasive procedure, there may be a role for newer cell-free fetal DNA aneuploidy screening. Although ffDNA is useful for the detection of certain karyotype abnormalities, it is not able to detect a wide range of less common karyotype abnormalities, such as triploidy, trisomies of chromosomes other than 21,13, and 18 and partial deletions/duplications/inversions that would be diagnosable with traditional amniocentesis and karyotype analysis via cell culture.
• Infectious causes for IUGR are relatively uncommon. Maternal serology and/or amniotic fluid evaluation with microbial culture and polymerase chain reaction (PCR) testing should be considered in cases of midtrimester onset IUGR or when ultrasound findings suggestive of congenital infection are present.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
