INTRODUCTION — Fetal growth restriction (FGR, also called intrauterine growth restriction [IUGR]) is the term used to describe a fetus that has not reached its growth potential because of environmental factors. The origin of the problem may be fetal, placental, or maternal, with significant overlap among these entities.

A major focus of prenatal care is to determine whether a fetus is at risk for growth restriction and to identify the growth-restricted fetus. This is important because these fetuses are at increased risk of adverse perinatal outcome. In addition, FGR appears to be an antecedent to some adult-onset disorders, including hypertension, hyperlipidemia, coronary heart disease, and diabetes mellitus (Barker hypothesis [1]). (See "Infants with fetal (intrauterine) growth restriction" and "Possible role of low birth weight in the pathogenesis of primary (essential) hypertension".)

The most common obstetric definition of FGR is based on sonography: an estimated fetal weight below the 10^th percentile for gestational age; however, other definitions using a variety of criteria have been proposed. An abdominal circumference <10^th percentile for gestational age is another common definition. When a small fetus is detected, it can be difficult to distinguish between the fetus that is constitutionally small versus growth restricted. It is also difficult to identify the fetus that is not small but growth restricted relative to its genetic potential. Making the correct diagnosis is not always possible prenatally, but is important prognostically and for estimating the risk for recurrence.

This topic will describe normal fetal growth and discuss the definition, classification, and diagnosis of FGR, as well as screening for the disorder. The etiology, management, and prognosis of FGR are reviewed separately.

●(See "Fetal growth restriction: Evaluation and management".)

●(See "Infants with fetal (intrauterine) growth restriction".)

NORMAL FETAL GROWTH — Fetal growth reflects the interaction of the fetus's predetermined growth potential and its modulation by the health of the fetus, placenta, and mother. Population-based intergenerational studies of birth weight have concluded that genetic factors account for 30 to 50 percent of the variation in birth weight, with the remainder due to environmental factors [2-5]. Maternal genes influence birth weight more than paternal genes, but both have an effect.

Fetal growth velocity is defined as the rate of fetal growth over a given time interval. In terms of individual biometric measurements, the rate of change in biparietal diameter (BPD), head circumference (HC), femur length (FL), and abdominal circumference (AC) initially peaks at 13, 14, 15, and 16 weeks of gestation, respectively [6]. BPD, HC, and AC then have a second acceleration in growth at 19 to 22, 19 to 21, and 27 to 31 weeks, respectively.

Estimated fetal weight growth velocity peaks at around 35 weeks. In general, normal growth in singletons increases from approximately 5 g/day at 14 to 15 weeks of gestation to 10 g/day at 20 weeks and 30 to 35 g/day at 32 to 34 weeks, after which the daily increase in weight decreases [7].

DEFINITION AND CLASSIFICATION OF FGR

Definition — The most common obstetric definition of FGR is an estimated weight below the 10^th percentile for gestational age in the second half of pregnancy [8], although other definitions employing a variety of criteria have been advocated (eg, <5^th percentile, <3^rd percentile) [9,10]. An abdominal circumference (AC) <10^th percentile for gestational age is another common definition [11,12].

Accurate assessment of gestational age is critical to the diagnosis of FGR, given that normal and abnormal fetal size are defined, in part, by comparing the fetal weight of the index fetus with that of other fetuses of the same gestational age. A detailed discussion of determination of gestational age can be found separately. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight".)

Limitations — The use of a percentile to define FGR is problematic because it does not distinguish among fetuses who are constitutionally small versus small because of a pathologic process that has kept them from achieving their genetic growth potential versus not small but kept from achieving their genetic growth potential by a pathologic process. As many as 70 percent of fetuses estimated to weigh below the 10^th percentile for gestational age are small simply due to constitutional factors (eg, maternal ethnicity, parity, or body mass index) and are not at high risk of perinatal mortality and morbidity [13]. There is a real possibility of misclassifying these normally nourished, healthy, but constitutionally small, fetuses as growth restricted. By comparison, a malnourished fetus whose estimated weight is slightly greater than the 10^th percentile may be misclassified as appropriately grown and at low risk of adverse perinatal outcome, even though its weight may be far below its genetic potential. A similar argument can be made when the AC is <10^th percentile for the gestational age.

An additional problem is that use of percentiles requires an appropriate reference, but there is little consensus on which reference should be used. Available references have been based on birth weights across gestation in a low-risk population (standard reference curve) or in an unselected population (population reference curve), on ultrasound-estimated fetal weights (EFW) across gestation, and on a customized standard [14,15]. The major flaw of birth weight reference standards is that infants who are born preterm are born early because of a pathologic process that often results in growth restriction. Ultrasound-based standards avoid this bias but are limited by the inaccuracy and imprecision of ultrasound-EFW.

Classification — Regardless of the FGR definition used, FGR may be classified as early or late and as symmetric or asymmetric:

●Early FGR refers to diagnosis before 32 weeks of gestation, in the absence of congenital anomalies.

●Late FGR refers to diagnosis at ≥32 weeks of gestation, in the absence of congenital anomalies.

●Symmetric FGR comprises 20 to 30 percent of FGR and refers to a growth pattern in which all fetal organs are decreased proportionally due to global impairment of cellular hyperplasia early in gestation.

Symmetric FGR is thought to result from a pathologic process manifesting early in gestation.

●Asymmetric FGR comprises the remaining 70 to 80 percent of the FGR population and is characterized by a relatively greater decrease in abdominal size (eg, liver volume and subcutaneous fat tissue) than in head circumference.

Asymmetric fetal growth is thought to result from the capacity of the fetus to adapt to a pathologic environment late in gestation by redistributing blood flow in favor of vital organs (eg, brain, heart, placenta) at the expense of nonvital fetal organs (eg, abdominal viscera, lungs, skin, kidneys) [16,17].

Undoubtedly, some overlap exists between these two entities.

SCREENING

Rationale — Ideally, prenatal detection of FGR will provide an opportunity to employ interventions to reduce the morbidity and mortality associated with this problem. Adverse outcomes include fetal demise, preterm birth, perinatal asphyxia, poor thermoregulation, hypoglycemia, polycythemia/hyperviscosity, impaired immune function, neonatal death, neurodevelopmental delay, and some adult-onset disorders. (See "Fetal growth restriction: Evaluation and management", section on 'Prognosis' and "Infants with fetal (intrauterine) growth restriction".)

As discussed below, the ability of screening and appropriate intervention to reduce the frequency of any of these outcomes has not been proven. Harms of screening include overdiagnosis of FGR, leading to parental anxiety and unnecessary, costly, and/or potentially harmful interventions (eg, antenatal fetal testing, induction of labor, iatrogenic preterm delivery).

Screening tests

Symphysis-fundal height measurement with selective ultrasonography — Measurement of the distance between the upper edge of the pubic symphysis and the top of the uterine fundus using a tape measure is a simple, inexpensive, and widespread technique performed during antenatal care to detect FGR, as well as other disorders that result in size/date discrepancy. The first suspicion of FGR often arises when this length is noted to be discordant with the expected size for dates. Discordancy has been defined in various ways; the most common criterion is a fundal height in centimeters that is at least 3 centimeters less than the gestational age in weeks (eg, fundal height 32 cm at 36 weeks of gestation) [18]. Alternatively, a fundal height measurement below the 3^rd or 10^th percentile for gestational age can be used: The INTERGROWTH-21^st Project International published printable symphysis-fundal height measurement standards for the 3^rd, 10^th, 50^th, 90^th, and 97^th percentiles using eight urban populations of healthy, well-nourished women [19].

The performance of fundal height measurements for screening for FGR is controversial. A systematic review concluded evidence was inadequate (one randomized trial) to evaluate the effectiveness of this technique versus abdominal palpation for detecting abnormal fetal growth [20]. Observational studies using symphysis pubis-fundal height measurements have reported a wide range of sensitivities: 13 to 86 percent of small fetuses were detected [18,21-28]. Factors that may affect sensitivity include maternal body mass index, bladder volume, parity, and ethnic group [26,27,29,30].

This technique appears to perform best when all of the measurements are obtained by the same clinician using the unmarked side of the tape (to reduce bias [31]) and plotted to reflect fetal growth for the individual patient ("customized"), rather than against a standardized norm [32,33].

Universal ultrasonography — Routine universal performance of ultrasound examination is an alternative method of screening for FGR. There is no consensus on the timing or number of screening examinations. In general, if two screening examinations are performed after the 18- to 22-week fetal anatomic survey, they are obtained at approximately 32 and 36 weeks of gestation [34]. If one examination is obtained, it is obtained between 32 and 36 weeks of gestation, and the predictive performance is higher nearer to 36 weeks [35].

Individualized growth assessment is an investigational screening approach that requires at least three ultrasound examinations. It establishes sonographic standards for multiple biometric parameters in a specific fetus during at least two time points in the second trimester, when fetal growth is linear [36]. Third-trimester measurements are then compared with those predicted by the second-trimester measurements for the specific fetus, not with a population standard, thus using the fetus as its own control. The Individualized Growth Assessment Program software is used to interpret the data. If a fetal growth disorder has already occurred during the second trimester, the estimate of growth potential will be compromised, but this can be detected by the software [37]. No data are available on the clinical use of this tool to characterize abnormal growth and its relationship to physiologic changes, perinatal complications, and long-term disabilities.

Our approach to screening — Our approach to screening for FGR is described in the algorithm (algorithm 1). This approach is generally consistent with pregnancy guidelines from many countries, including the United Kingdom, Canada, France, and the United States, which recommend screening for FGR using risk assessment for impaired fetal growth (table 1) and serial fundal height measurements at each prenatal visit. In addition:

●For women at high risk for FGR, an ultrasound examination is performed to estimate fetal weight and provide a detailed sonographic assessment of the fetus, placenta, and amniotic fluid at least once or twice in the third trimester (and as often as every three to four weeks), as well as when a lag in fundal height is detected. The frequency of ultrasound examination within this range depends on the clinician’s assessment of the patient’s level of risk for FGR. The information from ultrasound examination is used to support or exclude the diagnosis of FGR.

●For women who are not at high risk for FGR, an ultrasound examination is performed when a lag in fundal height is detected, the fundal height cannot be palpated (eg, patient with obesity), or the fundal height is not reliable (eg, large or multiple fibroids) [38,39].

Evidence — Universal ultrasonography in late pregnancy (after 24 weeks) is not generally recommended because the test has low sensitivity and a clear outcome benefit has not been proven:

●In a 2019 meta-analysis of 21 cohort studies of screening ultrasound at ≥32 weeks of gestation in low-risk or nonselected singleton pregnancies, pooled sensitivities for abdominal circumference (AC) and estimated fetal weight (EFW) <10^th percentile for birth weight <10^th percentile were similar and poor (AC 35 percent, 95% CI 20-52; EFW 38 percent, 95% CI 31-46) [40]. Pooled specificity for AC was 97 percent (95% CI 95-98) and for EFW was 95 percent (95% CI 93-97). Modeled sensitivities of AC and EFW <10^th percentile at a 10 percent false-positive rate were 78 and 54 percent, respectively. Perinatal outcome was not assessed.

●In a previous meta-analysis of 13 controlled trials including nearly 35,000 women, perinatal mortality was similar for patients undergoing routine versus no/concealed/selective ultrasonography (risk ratio 1.01, 95% CI 0.67-1.54); none of the trials reported on neurodevelopmental outcomes at age 2 [34]. The absence of benefit may be due to the poor diagnostic performance of the screening test, lack of an effective intervention when FGR is diagnosed, and deficiencies in study design. A subsequent prospective study reported sensitivity for detection of small for gestational age infants was higher with universal than with selective ultrasound screening, but this did not lead to a significant reduction in composite severe adverse perinatal outcome [41].

DIAGNOSIS — Sonographic estimation of either fetal weight <10^th percentile for gestational age or abdominal circumference (AC) <10^th percentile for gestational age is the best finding on which to base the diagnosis of FGR. A population-based fetal growth reference should be used; we prefer the Hadlock formula to the INTERGROWTH-21^st, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the World Health Organization (WHO) standards [42-44].

The following findings should also be considered to increase confidence in the diagnosis:

●The lower the percentile, the more likely the diagnosis is FGR rather than a constitutionally small fetus. (See 'Estimated fetal weight' below.)

●Some findings on imaging, such as body proportion ratios (discussed below), can support the diagnosis of asymmetric FGR but are likely to overlook fetuses with symmetric FGR. As discussed above, asymmetric FGR occurs in 70 to 80 percent of the FGR population, while symmetric FGR comprises the remaining 20 to 30 percent of growth-restricted fetuses.

●Information from the maternal history (table 1) and from a customized growth curve and assessment of amniotic fluid volume may improve diagnostic performance by helping to distinguish between the constitutionally small fetus, the growth-restricted fetus, and the fetus that is not small but not achieving its growth potential. (See 'Customized growth curve' below and 'Amniotic fluid volume' below.)

●Findings on Doppler velocimetry of the umbilical artery are insensitive diagnostically [45-47], but can still be useful as they are predictive of need for intervention and outcome. Overall, it is reasonable to assume that a fetus <10^th percentile with a normal growth curve over three weeks, normal amniotic fluid volume, absence of risk factors for FGR, and normal Doppler velocimetry is at low risk of the adverse outcomes related to FGR, even if affected. By comparison, the fetus <10^th percentile with a lagging growth curve, oligohydramnios, and risk factors for FGR is probably affected and at high risk of complications if Doppler velocimetry is abnormal. (See 'Doppler velocimetry' below.)

A meta-analysis comparing estimated fetal weight (EFW) versus AC for diagnosis of FGR concluded that both have theoretical disadvantages and advantages [40]. AC may be more susceptible to expected value bias because measurement can be technically challenging, but it reflects liver size and abdominal subcutaneous fat storage and is strongly related to fetal nutritional status. Because EFW combines multiple biometric measurements (AC, biparietal diameter, head circumference, and femur length), it is susceptible to the inherent measurement errors of each variable, thus potentially resulting in an overall worse predictive performance. However, EFW is more consistent with the newborn standards used to define small for gestational age since pediatricians do not typically measure AC. Based on these and other data, the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists consider either sonographic EFW or AC below the 10^th percentile for gestational age an acceptable threshold for suspecting FGR [12].

POTENTIAL SONOGRAPHIC FINDINGS IN FGR — A variety of sonographic parameters have been used to diagnose FGR. The technique for measuring these parameters and calculating fetal weight can be found separately. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight", section on 'Sonographic assessment of fetal weight'.)

A major limitation in interpreting the predictive value of sonographic findings for diagnosing FGR and comparing predictive values derived from different studies is that these values, like all laboratory values, depend upon the prevalence of FGR in the population studied. Thus, the post-test risk of FGR needs to take into account whether the study population was at low, moderate, or high risk of a fetal growth abnormality [48-50].

Estimated fetal weight — Estimated fetal weight (EFW) is the most common method of identifying the growth-restricted fetus since pediatricians use birth weight as their primary variable for defining growth restriction in the infant. The sensitivity of EFW for predicting FGR and adverse outcomes associated with FGR is highest when performed within one to two weeks of delivery and when the infant's birth weight is <3^rd percentile [51-55].

The sensitivity, specificity, positive, and negative predictive values of EFW for FGR <10^th percentile are approximately 90, 85, 80, and 90 percent, respectively [51-54]. By comparison, in one study, all infants with birth weight <3^rd percentile were identified prenatally [51]. In another study including 1116 consecutive fetuses with EFW <10^th percentile, all 8 mortalities occurred among the 826 fetuses with EFW <3^rd percentile, and EFW <3^rd percentile was the only sonographic weight-related definition consistently associated with adverse outcome [56].

Reference tables — Examples of fetal weight distribution standards by gestational age in the United States population are provided in the tables (table 2 and table 3); several such tables exist and are slightly different depending on the population studied and methods used. Investigators involved in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) fetal growth studies have published comprehensive tables of the 5^th, 10^th, 50^th, 90^th, and 95^th percentiles for EFW and individual biometric parameters by race and ethnicity [6].

Worldwide standards have also been proposed:

●The Fetal Growth Longitudinal Study developed an international growth and size standard by prospectively assessing fetal growth in over 4000 healthy, well-nourished women in eight countries with well-dated pregnancies at low risk of FGR who had no major pregnancy complications and delivered live, nonanomalous singletons [57]. Ultrasound examinations were obtained every 5 weeks from 14 to 42 weeks of gestation, and biometric measurements were used to derive the best fitting curves for the 3^rd, 50^th, and 97^th percentiles. They also provide a calculator that will compare an individual patient's biometric values with the international standard. Standards for newborn birth weight were also developed (table 4) [58].

●The World Health Organization has published charts for fetal growth and common ultrasound biometric measurements based on longitudinal data derived from 10 countries [59].

The validity of a worldwide standard has been challenged by the argument that adopting a universal standard for fetal growth "may lead to over diagnosing of both large- and small-for-gestational-age fetuses in terms of what is appropriate for a particular population, with a corresponding detrimental impact on clinical care" [60].

Customized growth curve — EFW is typically interpreted using population-based birth weight centiles, such as those provided above for the United States (table 2 and table 3); however, fetal weight is affected by multiple nonpathologic factors, including fetal sex and maternal parity, ethnicity, height, weight, and age [61-64]. Maternal characteristics have greater fetal effects than paternal characteristics.

A potentially better approach to interpretation of EFW is to utilize large population-based datasets that account for these variables and exclude the effects of pathologic variables such as maternal smoking, hypertension, diabetes, and preterm birth. This allows interpretation of EFW in the context of the individual fetus's growth potential, rather than against a population-based birth weight distribution. The optimal weight and range of normal around this weight for a specific fetus can be estimated for each gestational age to create an ultrasound-based, customized, optimal growth curve. The actual EFW is then plotted on this optimized, customized curve to create the individual fetus's growth curve across gestation. Free software for calculating customized fetal weight percentiles can be downloaded from www.gestation.net.

Although no randomized trials of this approach have been performed [65], several studies have compared the use of population-based birth weight centiles with customized percentiles for prediction of growth restriction and perinatal morbidity. Although many of these studies have concluded that using a customized birth weight standard improves the identification of fetuses at risk of perinatal death and neonatal morbidity [66-75], others have not, and this conclusion remains controversial [10,42,76-78].

The reported improvement in prediction of perinatal outcome with use of customized growth curves may be related to better identification of the constitutionally small fetus through adjustment for maternal characteristics, or to use of an intrauterine (ultrasound) growth standard rather than a birth weight standard for classification of FGR. Since fetuses who are born preterm tend to have lower birth weights than fetuses of the same gestational age who remain in utero, using an intrauterine weight standard increases identification of FGR remote from term [79]. The higher perinatal mortality among infants classified as FGR by the customized reference is largely due to the inclusion of more preterm births in this group [71,80,81]. When adjusted for preterm birth, the use of customized fetal growth curves rather than population-based growth curves does not clearly improve identification of pregnancies at increased risk of neonatal morbidity and mortality [81].

Biometry

Abdominal circumference — When fetal growth is compromised, the fetal abdominal circumference (AC) is smaller than expected because of depletion of abdominal adipose tissue and a reduction in hepatic size from depletion of glycogen. Most studies report that reduced AC is the most sensitive single biometric indicator of FGR [82-87]. Small AC also correlates with morbidity associated with FGR: biochemical markers of hypoxia and acidemia are more common when the AC is below the 5^th percentile for gestational age [88].

●In a study of over 3600 pregnancies >25 weeks of gestation that had a single ultrasound examination performed within two weeks of delivery, AC measurement predicted a birth weight <10^th percentile for gestational age with sensitivity, specificity, positive, and negative predictive values of 61, 95, 86, and 83 percent, respectively [86]. Measurement of AC was more predictive of FGR than measurement of either head circumference (HC) or biparietal diameter (BPD) or the combination of AC with either one of these two variables.

AC is most sensitive for detection of FGR when it is asymmetric (sensitivity in asymmetric and symmetric FGR: 73 and 59 percent, respectively [48]) and when measured near term (sensitivity at 29 to 31 weeks and at term: 41 and 88 percent, respectively [89]), although the above study concluded that the optimal time to screen for FGR with AC was at approximately 34 weeks of gestation [86].

Biometric ratios — The HC/AC and femur length (FL)/AC ratios have been used to identify FGR and are most sensitive in asymmetric FGR. Since FGR related to uteroplacental insufficiency is often asymmetric, biometric ratios are generally better for predicting FGR related to uteroplacental insufficiency than for FGR from other etiologies, when FGR is often symmetric.

HC/AC ratio — In asymmetric FGR, the size of the liver tends to be disproportionately small compared with the HC and length of the femur, which are initially spared from the effects of nutritional deficiency [90].

The HC/AC ratio decreases linearly throughout pregnancy; a ratio >2 standard deviations (SD) above the mean for gestational age is considered abnormal. One prospective study of the HC/AC ratio for detecting asymmetric FGR due to uteroplacental insufficiency reported normal ratios in 79 percent of fetuses, none of whom were FGR at birth; the remaining 21 percent had abnormal ratios and were diagnosed correctly as FGR [91]. By contrast, the sensitivity, specificity, positive, and negative predictive values of an abnormal HC/AC in a population with FGR of mixed etiologies were 36, 90, 67, and 72 percent, respectively [52].

Not all fetuses with an elevated HC/AC ratio have asymmetric FGR. Macrocephaly from an increase in the size of any of the components of the cranium (brain, cerebrospinal fluid, blood, or bone) or increased intracranial pressure could also be associated with an increased HC/AC ratio and should be excluded. (See "Macrocephaly in infants and children: Etiology and evaluation".)

FL/AC ratio — The FL/AC ratio uses biometric parameters that relate to both weight and length in the prediction of FGR and is independent of gestational age in normally grown fetuses in the last half of pregnancy. An FL/AC ratio >23.5 percent has been reported to have sensitivity of 56 to 64 percent and specificity of 74 to 90 percent for identification of asymmetric FGR [92,93] but does not detect symmetric FGR. The sensitivity, specificity, positive, and negative predictive values of the 90^th percentile of FL/AC ratio in a mixed population of FGR fetuses were 30, 91, 14, and 96 percent, respectively [94-96].

Amniotic fluid volume — Oligohydramnios is one of the sequelae of FGR. The proposed mechanism is diminished fetal urination due to hypoxia-induced redistribution of blood flow to vital organs at the expense of less vital organs, such as the kidney [97,98]. (See "Oligohydramnios: Etiology, diagnosis, and management".)

In general, pregnancies with the most severe oligohydramnios have the highest perinatal mortality rate, incidence of congenital anomalies (especially of the urinary tract), and incidence of FGR [99]. Oligohydramnios combined with EFW <3^rd percentile is highly predictive of adverse outcome [56].

Oligohydramnios is difficult to assess accurately (ie, as determined by dye-dilution studies) and commonly occurs with complications of pregnancy other than FGR. In addition, a significant proportion (approximately 15 to 80 percent) of fetuses with FGR do not have decreased amniotic fluid volume. Although generally an insensitive marker for FGR [100,101], if oligohydramnios is present in the absence of ruptured membranes, congenital genitourinary anomalies, or prolonged pregnancy, FGR is the most likely etiology.

Doppler velocimetry — FGR may be associated with abnormal Doppler wave forms in maternal vessels (uterine arteries) and fetal vessels (umbilical arteries, middle cerebral arteries, ductus venosus) when the etiology is placental dysfunction related to progressive obliteration of the villus vasculature. Assessment of Doppler flow with appropriate intervention can reduce perinatal mortality in these pregnancies. Doppler findings in FGR and management of FGR based on these findings are reviewed in detail separately and briefly summarized below. (See "Fetal growth restriction: Evaluation and management", section on 'Doppler velocimetry'.)

●Umbilical artery – When 30 percent of the villous vasculature ceases to function, an increase in umbilical artery resistance leading to reduced end-diastolic flow is consistently seen and is a weak predictor of adverse outcome in FGR. When 60 to 70 percent of the villous vasculature is obliterated, umbilical artery diastolic flow is absent or reversed, and fetal prognosis is poor. Reversed diastolic flow is associated with poorer neonatal outcomes than absent diastolic flow. (See "Fetal growth restriction: Evaluation and management", section on 'Umbilical artery'.)

●Uterine artery – The systolic/diastolic (S/D) ratio of the uterine artery in normal pregnancies should be <2.7 after the 26th week of gestation. If the end-diastolic flow does not increase throughout pregnancy or a small uterine artery notch is detected at the end of systole, the fetus is at high risk for developing FGR [102]. Diastolic blood flow may be absent or even reversed with extreme degrees of placental dysfunction. Such findings are ominous and may precede fetal death or signal a high risk of abnormal fetal neurologic outcome [103].

●Fetal descending aorta – An elevated pulsatility index in the fetal descending aorta is associated with both FGR and adverse outcomes, such as severe FGR, necrotizing enterocolitis, nonreassuring fetal heart rate patterns, and perinatal mortality [104-112]. In one group of 30 fetuses with absent end-diastolic flow in the descending aorta, abnormal wave forms were detected at a mean of 80 days prior to the onset of fetal heart rate (FHR) abnormalities [108]. All of the neonates were growth restricted, and 66 percent had abnormal placentas with villous fibrosis and microfibrinous deposits.

The sensitivity and specificity of absent end-diastolic flow in the descending aorta for prediction of FGR with FHR abnormalities are approximately 85 and 80 percent, respectively [110-112]. These pregnancies are also characterized by higher rates of cesarean delivery, right ventricular failure, and perinatal mortality.

●Fetal middle cerebral artery – In the normally developing fetus, the brain is an area of low vascular impedance and the recipient of continuous forward flow throughout the cardiac cycle. Asymmetric FGR is likely caused by redistribution of fetal blood flow to the fetal brain at the expense of less essential areas, such as subcutaneous tissue, kidneys, and liver. Since the already low middle cerebral resistance has to drop even further to enhance cerebral blood flow, FGR may be associated with increased end-diastolic velocities and decreased S/D ratios in the middle cerebral arteries. (See "Fetal growth restriction: Evaluation and management", section on 'Middle cerebral artery'.)

●Cerebroplacental ratio – The cerebroplacental Doppler ratio (CPR) is the middle cerebral artery pulsatility index (or resistance index) divided by the umbilical artery pulsatility index (or resistance index). A low CPR indicates fetal blood flow redistribution (brain sparing) and is predictive of adverse neonatal outcome. (See "Fetal growth restriction: Evaluation and management", section on 'Cerebroplacental ratio'.)

●Fetal venous Doppler – Venous Doppler abnormalities are late, ominous circulatory findings in FGR. (See "Fetal growth restriction: Evaluation and management", section on 'Ductus venosus'.)

Other

Three-dimensional ultrasonography — Three-dimensional ultrasound appears to be highly promising in the clinical setting of FGR because it appears to provide more precise information regarding structural abnormality, organ volumetry, EFW, and oligohydramnios than standard two-dimensional techniques [113-123]. However, this modality is not widely available and has not been adequately assessed in large or controlled studies.

One study used this technique in 100 fetuses to compare birth weight predicted by calculating thigh volume with birth weight predicted by two-dimensional ultrasound using BPD, AC, and FL [119]. All infants were delivered within 48 hours of ultrasound examination. The best-fit formula for thigh volume in the prediction of birth weight was linear and was superior to commonly used two-dimensional formulas. The errors in birth weight prediction by three-dimensional ultrasound, Warsof's formula, Hadlock's formula, and Thurnau's formula were 0.7, 6.2, 6.7, and 20.8 percent respectively. In addition, three-dimensional ultrasound thigh volumetry was not influenced by oligohydramnios, fetal head engagement, or inaccurate AC measurement.

These results were confirmed in other studies that found three-dimensional thigh, femur, or humerus volume measurement was simple and more accurate than two-dimensional ultrasound methods in the prediction of fetal weight [120-123].

Soft tissue — FGR results in a decrease in both adipose tissue and muscle mass. Although measurement of fetal soft tissue is probably predictive of FGR, there are inadequate data for defining the best site for measurement or the sensitivity and specificity of soft tissue parameters.

Measurement of the fetal thigh circumference incorporates the contributions of both adipose and muscle. In one study, a thigh circumference measuring 2 SD below the mean had a sensitivity of 78 percent and a positive predictive value of 85 percent in the prediction of FGR [124].

Other potential soft tissue measurements include subcutaneous tissue thickness at the level of the fetal midcalf, midthigh, or abdominal wall, and cheek-to-cheek diameter [125,126]. A prospective study of 137 unselected pregnancies that underwent serial sonographic measurement of fetal subcutaneous abdominal fat found fetuses with subcutaneous fat <5 mm at 38 weeks of gestation were approximately fivefold more likely to be FGR [127]. The sensitivity and specificity for diagnosis of FGR were 76 and 67 percent, respectively. In addition, the frequency of neonatal morbidity (eg, meconium aspiration, hypoglycemia, hypothermia, poor feeding, and jaundice) was significantly higher in infants with adipose tissue depletion.

SPECIAL POPULATIONS

Suboptimally dated pregnancies — Biometric findings used to diagnose FGR are interpreted in the context of gestational age. When the gestational age is not known with reasonable certainty, a single ultrasound examination may not be able to distinguish a small for gestational age fetus from an appropriately grown fetus that is less far along in gestation than expected from menstrual dates.

Serial sonographic examinations at two-week intervals can be useful when pregnancy dating is suboptimal. Irrespective of gestational age, FGR is associated with a significantly smaller rate of change over time in estimated fetal weight and other biometric parameters than observed in fetuses who are appropriate for gestational age [101,128,129]. The presence of risk factors for FGR, oligohydramnios, and abnormal Doppler velocimetry support the diagnosis of FGR, whereas the absence of these findings suggests that the fetus is at the gestational age calculated from biometry.

Multiple gestation — Growth in multiple gestations diverges from that in singletons in the late second or early third trimester. Smallness of one or both fetuses of a multiple gestation can be related to any of the disorders that cause FGR in singleton pregnancies, as well as disorders unique to multiple gestations, such as unequal placental sharing or twin-twin transfusion. FGR in multiple gestations is reviewed separately. (See "Selective fetal growth restriction in monochorionic twin pregnancies" and "Twin pregnancy: Routine prenatal care", section on 'Screening for fetal growth restriction and discordance'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Fetal growth restriction".)

SUMMARY AND RECOMMENDATIONS

●The two most common definitions of suspected fetal growth restriction (FGR) are an estimated fetal weight below the 10^th percentile for gestational age and an abdominal circumference below the 10^th percentile for gestational age. The use of the 10^th percentile to define FGR is problematic because it does not distinguish among fetuses who are constitutionally small versus small because of a pathologic process that has kept them from achieving their growth potential versus not small but kept from achieving their growth potential by a pathologic process. However, the lower the percentile, the more likely the diagnosis of FGR rather than a constitutionally small fetus. (See 'Definition and classification of FGR' above and 'Diagnosis' above.)

●Symmetric FGR comprises 20 to 30 percent of FGR and refers to a growth pattern in which all fetal organs are decreased proportionally. Asymmetric FGR comprises the remaining 70 to 80 percent of the FGR population and is characterized by a relatively greater decrease in abdominal size than head circumference. (See 'Definition and classification of FGR' above.)

●Ideally, prenatal detection of FGR will provide an opportunity to employ interventions to reduce the morbidity and mortality associated with this problem; however, the benefit of screening for FGR has not been clearly established. (See 'Rationale' above.)

●We agree with pregnancy guidelines from many countries, including the United Kingdom, Canada, France, and the United States, which recommend risk assessment for impaired fetal growth (table 1) and serial fundal height measurements at each prenatal visit (algorithm 1).

In women at high risk for FGR, detailed sonographic assessment of the fetus, placenta, and amniotic fluid is performed once or twice in the third trimester and when a lag in fundal height is detected. In the general/low-risk obstetric population, ultrasound examination is recommended only when a lag in fundal height is detected. (See 'Our approach to screening' above and 'Screening tests' above.)

●Information from the maternal history (table 1) and from a customized growth curve and assessment of amniotic fluid volume may improve diagnostic performance by helping to distinguish between the constitutionally small fetus, the growth-restricted fetus, and the fetus that is not small but not achieving its growth potential (see 'Customized growth curve' above and 'Amniotic fluid volume' above). Findings on Doppler velocimetry of the umbilical artery are insensitive diagnostically but predictive of outcome (see 'Doppler velocimetry' above). Overall, it is reasonable to assume that a small fetus with a normal growth curve over three weeks, normal amniotic fluid volume, and normal Doppler velocimetry is at low risk of FGR and complications associated with FGR, especially in the absence of risk factors for FGR, whereas the small fetus with a lagging growth curve, oligohydramnios, and maternal risk factors for FGR is probably affected and at high risk of complications if Doppler velocimetry is abnormal. (See 'Diagnosis' above.)