Fetal Growth Restriction

Maternal Impacts

Placental dysfunction affects several aspects of maternal adaptation to pregnancy. Associations between poor placentation with suboptimal maternal volume expansion, increased vascular reactivity, and a “flat” curve on the glucose tolerance test have been described. Abnormalities of placental vascular development are of special interest because they can be detected by Doppler ultrasound of the uterine arteries and frequently predate clinical disease ( Fig. 30.2 ). When trophoblast invasion remains confined to the decidual portion of the myometrium, maternal spiral and radial arteries fail to undergo the physiologic transformation into low-resistance vessels, which is generally expected by 22 to 24 weeks. Maternal placental floor infarcts, fetal villous obliteration, and fibrosis each increase placental blood flow resistance, producing a maternal-fetal placental perfusion mismatch that decreases the effective exchange area. With progressive vascular occlusion, fetoplacental flow resistance is increased throughout the vascular bed, and eventually, metabolically active placental mass is reduced. The diagnostic and screening utility of ultrasound findings suggestive of such pathology are discussed later.

Fetal Impacts

When placental dysfunction compromises nutrient delivery and triggers fetal mobilization of hepatic glycogen stores, physical manifestation of growth delay becomes clinically apparent. In addition to the cardinal sign of FGR, metabolic, endocrine, hematologic, cardiovascular, and behavioral manifestations of placental insufficiency have been described that relate to the severity and duration of placental dysfunction. Of these, cardiovascular and central nervous system (CNS) responses are best studied because their noninvasive assessment is readily achieved by multivessel Doppler, gray-scale ultrasonography, and fetal heart rate (FHR) analysis and can therefore be used for fetal surveillance. Appreciating the variety of fetal manifestations helps to understand the potential limitations of antenatal surveillance and provides a basis on which to appreciate the possible short- and long-term impacts of placental insufficiency.

Metabolic manifestations occur early in growth-restricted fetuses. This is because with mild to moderate decline in uterine nutrient delivery, fetal supply is compromised first, whereas placental nutrition is preferentially maintained. With progression of placental insufficiency, nutrient deficits become universal and result in decreased fetal and placental size. Accordingly, with mild restrictions in oxygen and glucose supply, fetal demands are still met by increased fractional extraction. When uterine oxygen delivery falls below a critical value (0.6 mmol/min per kilogram fetal body weight in sheep), fetal oxygenation begins to fall and is eventually accompanied by fetal hypoglycemia. The initial mild hypoglycemia results in a blunted fetal pancreatic insulin response that promotes gluconeogenesis from hepatic glycogen stores. The minimal hepatic glycogen stores in the fetus are quickly depleted as glucose and lactate are preferentially diverted to the placenta. An increasing nutrient deficit leads to worsening fetal hypoglycemia, which decreases the maintenance of fetal oxidative metabolism and placental nutrition. With a more significant limitation of oxidative metabolism associated with downregulation of placental transport mechanisms and intensifying hypoglycemia, the use of other fetal energy sources becomes necessary, and more widespread metabolic consequences ensue. Limitation of amino acid transfer and breakdown of endogenous muscle protein to obtain gluconeogenic amino acids depletes branched-chain and other essential amino acids. Simultaneously, lactate accumulates because of the limited capacity for oxidative metabolism. Placental transfer of fatty acids loses its selectivity, particularly for essential fatty acids. Reduced utilization leads to increased fetal free fatty acid and triglyceride levels with a subsequent failure to accumulate adipose stores. In this setting of advancing malnutrition, cerebral and cardiac metabolism of lactate and ketones is upregulated to remove these accumulating products of anaerobic metabolism. Acid-base balance can be maintained as long as acid production is met by sufficient buffering capacity of fetal hemoglobin and an equal disposition by the various organs. Thus metabolic compromise progresses from simple hypoglycemia, hypoxemia, and decreased levels of essential amino acids to overt hypoaminoacidemia, hypercapnia, hypertriglyceridemia, and hyperlacticemia. The lactate production is exponentially correlated to the degree of acidemia that generally results from this metabolic state. A summary of metabolic responses is provided in Table 30.1 .

Fetal endocrine manifestations of placental insufficiency are relevant because they are responsible for the downregulation of growth and developmental processes. Decreases in fetal glucose and amino acids indirectly downregulate insulin and insulin-like growth factors I and II as the principal endocrine regulators of longitudinal growth. Leptin-coordinated deposition of fat stores is similarly affected. In addition, pancreatic cellular dysfunction leads to decreased insulin/glucose ratio and impaired fetal glucose tolerance. Significant elevations of corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol and a decline in active vitamin D and osteocalcin are proportional to the severity of placental dysfunction. These hormonal imbalances are believed to have additional negative impacts on linear and growth, bone mineralization, and the potential for postpartum catch-up growth.

In growth-restricted fetuses, declining function at all levels of the thyroid axis correlates to the degree of hypoxemia. Thyroid gland dysfunction may develop as indicated by low levels of thyroxine and triiodothyronine despite elevated thyroid-stimulating hormone levels. In other instances, central production of thyroid-stimulating hormone may be responsible for fetal hypothyroidism. Finally, downregulation of thyroid hormone receptors may limit the biologic activity of circulating thyroid hormones in specific target tissues such as the developing brain.

Elevations in serum glucagon, adrenaline, and noradrenaline and stimulation of the fetal glucocorticoid axis have immediate effects that promote the mobilization of hepatic glycogen stores and peripheral gluconeogenesis. However, persistent alterations of these hormones may have a causative relationship with the development of diabetes and vascular complications in adult life.

Fetal hematologic responses to placental insufficiency are important because they initially provide a compensatory mechanism for hypoxemia and acidemia but eventually become contributory to the escalation of placental vascular dysfunction. Fetal hypoxemia is a trigger for erythropoietin release and stimulation of red blood cell (RBC) production through both medullary and extramedullary sites, which results in polycythemia. Oxygen carrying and the buffering capacity are increased through the elevation in hemoglobin count. If extramedullary hematopoiesis is increasingly induced by prolonged tissue hypoxemia and/or acidosis, the nucleated red blood cell (NRBC) count rises owing to the escape of these cells from these sites. Thus elevated NRBC counts correlate with metabolic and cardiovascular status and are independent markers for poor perinatal outcome. In advanced placental insufficiency, more complex hematologic abnormalities supervene that may result from dysfunctional erythropoiesis, placental consumption of platelets, and vitamin and iron deficiency. Subsequently, fetal anemia and thrombocytopenia are observed, particularly in fetuses with marked elevation of placental blood flow resistance and evidence of intraplacental thrombosis, which suggests a causative relationship. Increase in whole blood viscosity, decrease in RBC membrane fluidity, and platelet aggregation may be important precursors in the acceleration of placental vascular occlusion and dysfunction and therefore the rate of clinical progression.

Growth-restricted fetuses also show evidence of immune dysfunction at the cellular and humoral level. Decreases in immunoglobulin, absolute B-cell counts, total white blood cell counts, and neutrophil, monocyte, and lymphocyte subpopulations—as well as selective suppression of T-helper and cytotoxic T cells—are proportional to the degree of acidemia. These immune deficiencies explain the higher susceptibility of growth-restricted neonates to infection after delivery.

Fetal cardiovascular responses to placental insufficiency can be subdivided into early and late, based on the degree of deterioration of cardiovascular status and the associated derangement of fetal acid-base balance (see later). Early responses are typically adaptive in nature and result in preferential nutrient streaming to essential organs. The combination of elevated placental blood flow resistance and impaired transplacental gas transfer has several effects on the fetal circulation. Normally, nutrient-rich oxygenated blood enters the fetus via the umbilical vein and reaches the liver as the first major organ. One of the earliest cardiovascular signs of placental insufficiency is a decrease in the magnitude of umbilical venous flow volume. In response to these changes in umbilical venous nutrition content and blood flow volume, the proportion of umbilical venous blood diverted through the DV toward the fetal heart increases. This change in venous shunting across the DV increases the proportion of nutrient-rich umbilical venous blood that bypasses the liver and reaches the left side of the heart through the foramen ovale. The presence of central shunts at the foramen ovale and ductus arteriosus allows changes in downstream blood flow resistance to affect the proportion of cardiac output that are delivered through each ventricle ( Fig. 30.3 ). Elevation of blood flow resistance in the pulmonary vascular bed and subdiaphragmatic circulation (lower body and placenta) increase right ventricular afterload. A drop in cerebral blood flow resistance decreases left ventricular afterload. As a consequence, shunting of nutrient-rich blood from the DV through the foramen ovale to the left side of the heart increases, and left ventricular output rises in relation to the right cardiac output. At the aortic isthmus, blood coming from the right ventricle through the ductus arteriosus is diverted toward the aortic arch, thereby supplementing this central shift in cardiac output from right to left. This relative shift in cardiac output toward the left ventricle that results in increased blood flow to the myocardium and brachiocephalic circulation has been termed redistribution, which indicates a compensatory mechanism in response to placental insufficiency.

Late circulatory responses are associated with deterioration of cardiovascular status and are predominantly observed in early-onset growth delay, which requires delivery prior to 34 weeks. Redistribution is effective only as long as adequate forward cardiac function is maintained. Marked elevations in placental blood flow resistance and progressive placental insufficiency can lead to an impairment of cardiac function. When this occurs, several aspects of cardiovascular homeostasis can be affected. Ineffective preload handling and elevation in central venous pressure may result from ineffective redistribution, a measurable decline in cardiac output, and a decline in cardiac forward function. The hallmark of this advancing deterioration in cardiovascular state is loss of diastolic forward flow in the umbilical circulation and a marked decline of forward flow in the venous system. Finally, myocardial dysfunction and cardiac dilatation may result in holosystolic tricuspid insufficiency and spontaneous FHR decelerations, followed by fetal demise.

Fetal organs also have the ability to regulate their individual blood flow through autoregulation. Such autoregulatory mechanisms have been identified in the myocardium, adrenal glands, spleen, liver, celiac axis, mesenteric vessels, and kidneys. These autoregulatory mechanisms are evoked at different levels of compromise, and their effect is typically complementary to central blood flow redistribution by enhancing perfusion of vital organs as long as cardiovascular homeostasis is maintained. A summary of Doppler findings and their physiologic significance in the context of placental insufficiency is provided in Table 30.2 .

TABLE 30.2

Arterial and Venous Doppler Indices

Index	Calculation
Arterial Doppler Indices
Systolic/diastolic (S/D) ratio
Resistance index (RI)
Pulsatility index (PI)
Venous Doppler Indices
Inferior vena cava preload index
Ductus venosus preload index
Inferior vena cava and ductus venosus pulsatility index for veins (PIV)
Inferior vena cava and ductus venosus peak velocity index for veins (PVIV)
Percentage reverse flow

Fetal behavioral responses to placental insufficiency and characteristics of the FHR reflect developmental status and undergo significant changes with advancing gestation. Progressive sophistication of fetal behavior and increasing variation of the FHR reflect differentiation of central regulatory centers and expansion of central processing capability. Normally, behavioral milestones progress from the initiation of gross body movements and fetal breathing in the first trimester to coupling of fetal behavior (e.g., heart rate reactivity) and integration of rest-activity cycles into stable behavioral states (states 1F through 4F) by 28 to 32 weeks’ gestation (see Chapter 11 ). A steady decrease in baseline heart rate that reflects increasing vagal tone accompanies these developments. In addition, short- and long-term variability and variation, as well as the amplitude of accelerations, increase with advancing gestation, which reflects increased central processing. With the completion of these milestones, heart rate reactivity by traditional criteria is present in 80% of fetuses by 32 weeks’ gestation. Differences in maturational state and behavioral state, disruption of neural pathways, and declining oxygen tension may all modulate or even abolish fetal behavior or heart rate characteristics.

Because variations of fetal behavior and the FHR may be due to several factors, observation of several variables over a sufficient length of time is necessary to separate physiologic from pathologic variation. Biophysical profile (BPP) scoring quantifies fetal behavior by assessing tone, movement, breathing activity, and FHR reactivity in an observation period of at least 30 minutes (see Chapter 27 ). Amniotic fluid volume (AFV) assessment has traditionally been a part of the BPP. From the second trimester onward, AFV is primarily related to fetal urine production and therefore renal perfusion (see Chapter 28 ). Thus AFV assessment provides an indirect assessment of renal/vascular status and constitutes the main longitudinal monitoring component of the BPP (see later). Visual FHR analysis is associated with interobserver and intraobserver variability. These are circumvented by computerized cardiotocography (cCTG) analysis of the FHR. The cCTG assesses short-term, long-term, and mean minute variation and periods of high variation in addition to traditional FHR parameters that also allow longitudinal observations.

In growth-restricted fetuses with chronic hypoxemia and mild placental dysfunction, the primary CNS response is a delay in all aspects of CNS maturation. With the help of computerized research tools, a delay in behavioral development has been documented under such circumstances. The combination of delayed central integration of FHR control, decreased fetal activity, and chronic hypoxemia results in a higher baseline heart rate with lower short- and long-term variation (on computerized analysis) and delayed development of heart rate reactivity. These maturational differences in FHR parameters are particularly evident between 28 and 32 weeks.

Despite the maturational delay of some aspects of CNS function, several centrally regulated responses to acid-base status are still preserved. Therefore the growth-restricted fetus still maintains behavioral responses to a decline in acid-base status independently of the cardiovascular status. In contrast, the declining AFV that commonly accompanies the sequential loss of biophysical variables appears to be related to renal blood flow and the degree of vascular redistribution .

With worsening fetal hypoxemia, a decline in global fetal activity initiates the cascade of late behavioral responses characteristic of placental insufficiency. With further deepening hypoxemia, fetal breathing movement ceases.

Gross body movements and tone decrease further until they are no longer observed in the traditional examination period. Traditional FHR variables are frequently abnormal by this time. Reduction of global fetal activity and loss of fetal coupling (absence of heart rate reactivity and fetal breathing movements) are typically observed at a mean pH between 7.10 and 7.20. Loss of tone and movement is characteristic as the pH drops further. Late decelerations of the FHR may develop because of a relative drop in oxygen tension that exceeds 8 torr (see Chapter 15 ). Spontaneous decelerations as a result of direct depression of cardiac contractility or “cardiac” late decelerations typically herald fetal demise.

Fetal Biometry

Ultrasound criteria have emerged as the diagnostic standard used in the identification of FGR. For this purpose, sonographic measurements of fetal bony and soft structures are related to reference ranges for gestation. The primary measurements used to evaluate fetal growth include those of the fetal head, AC, and long bones. The most important calculated ultrasound variable of fetal growth is the sonographically estimated fetal weight (SEFW), and numerous investigators have identified distinct fetal ultrasound parameters that are useful in the calculation of the SEFW. All of the techniques incorporate an index of abdominal size as a variable contributing to the estimation of fetal weight. Population-specific formulae generate reference limits that generally have 95% confidence limits that deviate approximately 15% around the actual value.

Accurate estimation of fetal growth from these fetal measurements requires knowledge of the gestational age as a reference point to calculate percentile ranks. An estimated date of confinement (EDC) should be based on the last menstrual period when the sonographic estimate of gestational age is within the predictive error (7 days in the first, 14 days in the second, and 21 days in the third trimester). Once the EDC is set by this method or by a first-trimester ultrasound, it should not be changed because such practice interferes with the ability to diagnose FGR.

Measurement of the biparietal diameter (BPD) alone is a poor tool for the detection of FGR. The physiologic variation in size inherent with advancing gestation is high. The majority of growth-restricted fetuses who present with asymmetric growth restriction and delayed flattening of the cranial growth curve would be detected relatively late. Factors that interfere with a technically adequate measurement of the BPD include alterations of the cranial shape by external forces (oligohydramnios, breech presentation) and direct anteroposterior position of the fetal head.

The head circumference (HC) is not subject to the same extrinsic variability as the BPD. The measurement technique is important because calculated HC measurements are systematically smaller than those directly measured; thus the nomogram selected should be based on measurements obtained using the same methodology. As a screening tool for FGR, the HC poses a similar problem as the BPD in that two-thirds of FGR fetuses with asymmetric growth pattern would be detected late. The transcerebellar diameter (TCD) is one of the few soft tissue measurements that correlate well with gestational age, being relatively spared from the effects of mild to moderate uteroplacental dysfunction.

The AC is the single best measurement for the detection of FGR . The most accurate AC is the smallest directly measured circumference obtained in a perpendicular plane of the upper abdomen at the level of the hepatic vein between fetal respirations. The AC percentile has both the highest sensitivity and negative predictive value for the sonographic diagnosis of FGR whether defined postnatally by birthweight percentile or ponderal index. Using the 10th percentiles as cutoffs, the AC has a higher sensitivity (98% vs. 85%) but lower positive predictive value (PPV) than the SEFW (36% vs. 51%). Its sensitivity is further enhanced by serial measurements at least 14 days apart. Because of its high sensitivity, some type of abdominal measurement should be part of every sonographic growth evaluation. Calculation of the ratio between the head and abdominal circumference (HC/AC ratio) has been proposed as a tool to increase detection of the fetus with asymmetric growth restriction ( Figs. 30.4 and 30.5 ). In the normally growing fetus, the HC/AC ratio exceeds 1.0 before 32 weeks’ gestation, is approximately 1.0 at 32 to 34 weeks’ gestation, and falls below 1.0 after 34 weeks’ gestation. In fetuses with asymmetric growth restriction, the HC remains larger than that of the body and results in an elevated HC/AC ratio, whereas the ratio remains normal in symmetric FGR, in which both direct measurements are equally affected (see Figs. 30.4 and 30.5 ). Using the HC/AC ratio, 70% to 85% of growth-restricted fetuses are detected, with a reduction in false-negative diagnoses. Thus, even when determined in the latter part of pregnancy, a single set of measurements can be very helpful in evaluating the status of fetal growth. However, both the sensitivity and the PPV of the HC/AC ratio for growth restriction does not equal either the AC percentile or the SEFW.

When measurement of the HC is difficult because of fetal position, comparisons can be made of the femur length (FL)—which is relatively spared in asymmetric FGR—to the AC. The FL/AC ratio is 22 at all gestational ages from 21 weeks to term; therefore this ratio can be applied without knowledge of the gestational age. An FL/AC ratio greater than 23.5 suggests FGR.

Several formulae have been devised to calculate the SEFW. Using a multifactorial equation and a measurement of abdominal size, a weight can be predicted and related to gestational age. Formulae that incorporate the FL may increase the accuracy of in utero weight estimation for the fetus with FGR. Because the SEFW cannot be measured directly but is calculated from a combination of directly measured parameters, the error in the estimate is increased. The accuracy of most formulae (±2 standard deviations [SDs]) is ± 10%, and none has proven superior to the first devised by Warsof and reported by Sheppard. As noted earlier, the SEFW has a lower sensitivity but higher PPV than the AC and does not add to the AC percentile for the diagnosis of FGR. However, an SEFW less than the 10th percentile provides a graphic image that makes it easy for both patient and referring physician to conceptualize. Therefore use of the estimated fetal weight (EFW) has become the most common method for characterizing fetal size and thereby growth abnormalities.

Reference Ranges That Define Fetal Growth

The importance in identifying the FGR fetus at risk for adverse outcome lies in the requirement for surveillance and active management of these pregnancies. An absolute threshold to define FGR can be applied to any of the fetal biometric parameters. These criteria have been statistically defined, rather than outcome based, and use either a threshold percentile ranking (nonnormative data) or a number of SDs below the mean (normative data) as cutoffs. SGA is defined as a birthweight below the population 10th percentile corrected for gestational age. This definition has also been extended into the prenatal period by using an SEFW less than the 10th percentile as an indicator of FGR. Because such an approach is purely based on a weight threshold, it can only serve as a screen for the identification of the small fetus at risk for adverse outcomes. Approximately 70% of infants with a birthweight below the 10th percentile are normally grown (i.e., constitutionally small) and are not at risk for adverse outcomes because they present one end of the normal spectrum for neonatal size. The remaining 30% consist of infants who are truly growth restricted and are at risk for increased perinatal morbidity and mortality. When the cutoff for an abnormal birthweight is adjusted to the third percentile, the proportion of true growth-restricted infants identified increases, whereas some with milder forms of FGR will be missed. The principal advantage of a lower percentile cutoff is the identification of fetuses at greatest need for antenatal surveillance. The overall arbitrary nature of percentile cutoffs is further emphasized by the increased mortality for birthweights through the 15th percentile with an odds ratio of 1.9 for mortality in newborns with birthweights between the 10th and 15th percentiles. Because the percentile cutoffs to define abnormal growth continue to be a matter of debate, risk assessment based on weight alone is further hampered by discrepancies between the SEFW and the actual birthweight. Live birthweight criteria do not appropriately describe SEFWs, and a significant association of preterm birth with FGR is apparent. The weights of preterm infants are not normally distributed as they are at term, which produces a significant discrepancy between birthweight-defined growth curves and SEFW-defined growth curves in preterm gestation. SEFW growth curves are generated from patient samples that represent the entire obstetric population at any gestational age. In contrast, preterm live birth normative data tables reflect only those individuals who have delivered under abnormal circumstances. Thus the SEFW growth curves consistently demonstrate higher fetal weights over the range of preterm gestation than do birthweight-generated growth curves. Therefore use of an SEFW cutoff less than the 10th percentile captures most fetuses at greater perinatal risk. For the AC, a cutoff of the 2.5 percentile is appropriate because reference ranges are based on a cross-section of small, appropriately grown preterm and term newborns. However, because reference limits are based on healthy women delivering appropriately nourished neonates at term, less than the 10th percentile cutoff is consistent with FGR.

Because of the limitation of population-based reference ranges to assess fetal growth , individualized growth models have been proposed by several investigators. The obvious advantage is the lack of dependency on population-based normative data and the ability to detect a true, singularly defined growth restriction even with EFWs greater than the 10th percentile for the population. Some of these models require three sequential sonograms. This includes baseline biometry in the second trimester, a second sonogram to establish growth potential for an individual morphometric parameter, and a third scan to identify a growth abnormality. Because this approach is cumbersome in clinical practice, other models have been developed that account for variables that contribute the majority of the variance to newborn size. These include early pregnancy weight, maternal height, ethnic group, parity, and sex. Using these variables and fetal growth patterns, the estimated size of a fetus of a given mother can be projected at term and estimated at any specific point in gestation. Deviations from this projected growth pattern can then be recognized. Overall, the diagnostic advantages of these individualized growth models have been questioned when compared with the sequential comparison of the percentile ranking of individual or composite growth parameters to population-based growth curves.

Fetal growth, as opposed to fetal size, is a dynamic process that requires more than a single evaluation for its estimation. The appropriate observation interval for the evaluation of fetal growth has been based on the assumptions that growth is continuous, rather than sporadic, and that the identification of growth is limited by the technical capability of the ultrasound equipment used to measure the fetus. The recommended interval between ultrasound evaluations of fetal growth is 3 weeks because shorter intervals increase the likelihood of a false-positive diagnosis.

In summary, the ability to correctly identify growth-restricted fetuses at risk for adverse outcome by weight estimates alone is limited. Individualized or sequential growth assessment performs better than a single measurement of fetal size. Improved stratification of risk requires the integration of additional diagnostic tests.

Fetal Anatomic Survey

The sonographic survey of fetal anatomy may provide a clue to the underlying etiology of FGR. The anatomic survey should focus on markers of aneuploidy, nonaneuploid syndromes, and fetal infection, as well as structural malformations. The relationship between aneuploidy and fetal anomalies such as omphalocele, diaphragmatic hernia, congenital heart defects, and sonographic markers such as echogenic bowel, nuchal thickening, and abnormal hand positioning are discussed in Chapter 9 . Abnormalities of skull contour, thoracic shape, or disproportional shortening of the long bones may be suggestive of a skeletal dysplasia. Markers for viral infection may be nonspecific but include echogenicity and calcification in organs such as the brain and liver. Identification of any of these abnormalities on ultrasound may help to establish a differential diagnosis and can identify underlying conditions that impact the prognosis.

Amniotic Fluid Assessment

From the second trimester onward, regulation of AFV is primarily dependent on fetal urine output, production of pulmonary fluid, and fetal swallowing (see Chapter 28 ). Placental dysfunction and fetal hypoxemia both may result in decreased perfusion of the fetal kidneys with subsequent oliguria and decreasing AFV. Two techniques of AFV assessment can provide important diagnostic and prognostic information (see Chapter 28 ). A 2-cm vertical pocket was considered normal, 1 to 2 cm was marginal, and less than 1 cm was decreased. Alternatively, AFV may be assessed by the sum of vertical pockets from the four quadrants of the uterine cavity. This four-quadrant amniotic fluid index (AFI) nomogram (see Fig. 28.4 ) is compared with gestational reference ranges. Despite the availability of these methods for estimating the AFV, an overall clinical impression of reduced amniotic fluid may be most important. Ultrasound criteria for a subjectively reduced AFV include a maximum vertical pocket less than 3 cm, the fetus in a flexion attitude with limited room for movement, a small or empty bladder and stomach, and molding of the uterus around the fetal body. In addition, movement of the transducer frequently generates uterine contractions, which may be associated with variable decelerations.

Overall, estimation of AFV in itself is a poor screening method for FGR or fetal acidemia. However, in clinical practice, it is an important diagnostic and prognostic tool. Oligohydramnios may be the first sign of FGR detected on ultrasonography preceding an assessment for lagging fetal growth. If gestational age is known, ultrasound assessment of fetal growth based on the HC, AC, FL, and SEFW can be performed. If gestational age is unknown, measurements of the FL/AC ratio and a single amniotic fluid pocket have to be used because they are independent of gestational age. Up to 96% of fetuses with fluid pockets less than 1 cm may be growth restricted. When growth delay is already suspected, assessments of AFV can help with a differential diagnosis. In the setting of small fetal size, abundant AFV suggests aneuploidy or fetal infection, whereas normal or decreased amniotic fluid is compatible with placental insufficiency. The volume of amniotic fluid also has prognostic significance for the course of labor. Groome and colleagues demonstrated that oligohydramnios associated with fetal oliguria is associated with a higher rate of intrapartum complications that may be attributed to reduced placental reserve.

Doppler Velocimetry

Similar to the assessment of AFV, the role of Doppler velocimetry in the management of FGR is unique because it serves as a diagnostic, as well as a monitoring, tool. Doppler flow-velocity waveforms may be obtained from arterial and venous vascular beds in the fetus. Arterial Doppler waveforms provide information on downstream vascular resistance, which may be altered because of structural changes in the vasculature or regulatory changes in vascular tone. The systolic/diastolic (S/D) ratio, the resistance index, and the pulsatility index (PI) are the three Doppler indices most widely used to analyze arterial blood flow resistance (see Table 30.2 ). An increase in blood flow resistance manifests with a relative decrease in end-diastolic velocity (EDV) increasing all three Doppler indices. Of these, the PI has the smallest measurement error and narrower reference limits. With extreme increases in blood flow resistance, end-diastolic forward flow velocity may be absent or reversed, referred to as absent end-diastolic velocity (AEDV) or reversed end-diastolic velocity (REDV; Fig. 30.6 ).

Venous Doppler parameters complement evaluation of fetal cardiovascular status by providing an assessment of cardiac forward function. Forward blood flow in the venous system is determined by cardiac compliance, contractility, and afterload and is characterized by a triphasic flow pattern that reflects pressure volume changes in the atria throughout the cardiac cycle. The descent of the AV ring during ventricular systole and passive diastolic ventricular filling generates the systolic and diastolic peaks respectively (the S-wave and the D-wave). The sudden increase in right atrial pressure with atrial contraction in late diastole causes a variable amount of reverse flow that produces a second trough after the D-wave (the a-wave; Fig. 30.7 ). The magnitude of forward flow during the atrial systole varies considerably in individual veins, and reversal may be physiologic in the inferior vena cava and hepatic veins but is always abnormal in the DV. Multiple venous Doppler indices have been described to characterize this complex waveform without any clear advantages of individual indices (see Table 30.2 ).

The vessels that are of primary importance in the differential diagnosis of placental dysfunction are the UA and the middle cerebral artery (MCA). Randomized trials and meta-analyses confirm that the combined use of fetal biometry and UA Doppler significantly reduces perinatal mortality and iatrogenic intervention because documentation of placental vascular insufficiency effectively separates growth-restricted fetuses that require surveillance and possible intervention from constitutionally small fetuses.

A free umbilical cord loop is examined with continuous or pulsed Doppler ultrasound far from the fetal and placental insertions. Most current ultrasound equipment allows concurrent use of color and pulsed Doppler with improved reproducibility of measurements. Vascular damage that affects approximately 30% of the placenta produces elevations in the UA Doppler index, whereas more marked abnormalities result in AEDV or REDV. Milder forms of placental vascular dysfunction, especially near term, may not produce elevation of UA blood flow resistance sufficient to be detectable by traditional Doppler methods. If placental gas exchange is significantly impaired, resulting in fetal hypoxemia, a decrease in MCA Doppler resistance may occur ( Fig. 30.8 ). Another Doppler index frequently used clinically to detect this condition is the ratio between UA pulsatility as an index of vasoconstriction in the placenta and MCA pulsatility as an index of vasodilation in the fetal brain. In milder forms of placental disease with near minimal increase in UA blood flow resistance, the cerebroplacental Doppler ratio (CPR) may decrease. Grammellini and coworkers demonstrated that a value less than 1.08 identified small fetuses at risk for adverse outcome. Subsequently, Bahado-Singh and coworkers indicated that the predictive accuracy of the CPR decreased after 34 weeks’ gestation. This is presumably attributable to an increasing number of growth-restricted fetuses who may have normal UA blood flow resistance near term but demonstrate isolated “brain sparing” as the only sign of placental insufficiency of oxygen transfer. These fetuses are at risk for adverse outcomes .

Because of the variable presentation of FGR across gestation, comprehensive Doppler assessment of placental function should include the umbilical and MCAs. For the UA, an abnormal test result is defined as a Doppler index measurement of greater than 2 SDs above the gestational age mean and/or a loss of EDV. As with growth curves, it is best to use nomograms developed from a local or comparable population. For the CPR and also for the MCA, a greater than 2-SD decrease of the index is considered abnormal. In a setting of small fetal size, these findings identify those fetuses at greatest risk for adverse outcome ( Figs. 30.9 to 30.12 ).