INTRODUCTION — Normal fetal growth is determined by the fetal genetic growth potential and influenced by maternal, fetal, and placental factors [1]. Fetal growth restriction (FGR) occurs when the genetic growth potential is not achieved due to an abnormality of any of these three factors. It occurs in up to 10 percent of pregnancies and is a major contributor to perinatal morbidity and mortality [2-4]. FGR is also associated with long-term morbidities, including neurodevelopmental delay in childhood and increased risks for cardiovascular disease, dyslipidemia, and diabetes mellitus in adulthood [5,6]. (See "Fetal growth restriction (FGR) and small for gestational age (SGA) newborns" and "Possible role of low birth weight in the pathogenesis of primary (essential) hypertension".)
Identification of FGR is an integral component of prenatal care. Although antenatal treatment is not available, fetal surveillance can be initiated upon diagnosis and timing of birth optimized to reduce the risk of stillbirth [4,7,8]. However, many cases are not detected antenatally, the risk for stillbirth is increased eightfold in undetected cases, and, even when the most severe cases are detected, these cases are associated with a high risk for adverse perinatal outcome [9-12].
This topic will address the screening and diagnosis of FGR. Postdiagnostic evaluation and management of FGR are reviewed separately. (See "Fetal growth restriction: Evaluation" and "Fetal growth restriction: Pregnancy management and outcome".)
ASSESSMENT OF FETAL GROWTH — Assessment of normal versus abnormal fetal growth requires accurate determination of both gestational age and fetal size and comparison with a growth standard.
●Assessment of gestational age – Verification of pregnancy dating is based on review of menstrual history and ultrasound biometry, in the absence of assisted reproductive techniques such as embryo transfer or in utero insemination. Ideally, pregnancy dating is based on the crown-rump length in the first trimester, but fetal biometry (eg, biparietal diameter, femur length) before 22+0 weeks of gestation is acceptable. Methods for prenatal assessment of gestational age and performance characteristics of each method are reviewed separately. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight".)
●Assessment of fetal size – Ultrasound is the standard method for assessing fetal size. The estimated fetal weight (EFW) is calculated using a formula incorporating ultrasound measurements of the biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL), typically in pregnancies ≥24 weeks of gestation [13]. The most commonly used nomogram for EFW in the United States is based on the Hadlock formula, which was developed based on observations at a single institution [14]. The inherent error between the calculated EFW and actual birth weight at the 95% confidence interval was greater than 14 percent across studies in which ultrasound EFW was documented within seven days of birth, and had both intraobserver and interobserver variability. This limitation contributes to both under- and overdiagnosis of fetal growth abnormalities [15,16]. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight", section on 'Sonographic assessment of fetal weight'.)
Since the diagnostic performance of prenatal ultrasound for detecting FGR is limited, the threshold for diagnosing FGR must sufficiently balance sensitivity and specificity to identify as many true-positive cases as possible while limiting the false-positive diagnoses. Although high sensitivity enables a greater proportion of fetuses at risk for adverse outcome and stillbirth to be monitored and delivered early when indicated, it may also lead to increased surveillance, cost, and possibly unnecessary intervention for normally grown fetuses [15].
●Comparison with a growth standard – The calculated EFW is compared with a reference growth standard to determine the percentile for gestational age. A growth standard can be programmed into the ultrasound machine at the clinical site so that EFW percentiles are automatically calculated in real-time.
Growth standards vary because some are based on ultrasound assessments of EFW across gestation (fetal growth standards) while others are based on birth weights of preterm, term, and postterm newborns (newborn growth standards) [17]. They also vary based on the population used to develop the standard. Several population-based studies have developed specific fetal growth nomograms for specific populations [18-20]. In 2022, a fetal growth standard reflecting the US population was created that accounts for racial and ethnic variation; future studies are necessary to determine if this recent standard improves outcomes [21].
A study that compared fetal and birthweight-derived standards concluded that neither accurately predicted neonatal morbidity and mortality, but intrauterine standards performed slightly better than birth weight standards [22]. A large multinational prospective observational longitudinal study conducted by the World Health Organization (WHO) to evaluate the trajectory of normal fetal growth showed significant variation in fetal growth among countries and that growth is impacted by maternal factors including parity, height, and weight, and by fetal sex [18]. In recognition of these observations, customized growth curves have been developed that adjust the reference curve based on these characteristics and thus potentially improve the accuracy of assessment of fetal size and growth over time [1]. However, comparative studies have reported conflicting data about use of customized growth curves compared with the Hadlock formula to increase the detection of small fetuses at higher risk for postnatal morbidities, thus continued use of population-based standards (such as Hadlock in the United States) is appropriate [2,21,23-26]. Regardless of the growth standard used, a proportion of fetuses will be mislabeled as being normally grown or having FGR due to the limitations of sonographic diagnosis.
DEFINITIONS
●FGR is broadly defined as an estimated fetal weight (EFW) or abdominal circumference (AC) <10th percentile for gestational age [27]. There is variation among international society guidelines, with some including AC thresholds <10th or ≤5th percentile alone as a diagnostic criteria [28,29].
●Severe FGR is defined as an EFW or AC <3rd percentile for gestational age. Fetuses in this category are at higher risk for perinatal morbidity and mortality regardless of gestational age at birth.
The presence of umbilical artery Doppler abnormalities also suggests that FGR is severe because these abnormalities (eg, pulsatility index >95th percentile, absent or reversed end-diastolic flow) are associated with an increased risk of adverse perinatal outcome [30].
●Early-onset FGR (in the absence of congenital anomalies) defines FGR identified before 32 weeks gestation [31]. It is considered at the severe end of the FGR spectrum since it is commonly associated with abnormal placental function and earlier fetal deterioration, leading to preterm birth. Pregnancies with early-onset FGR are at higher risk for preeclampsia and perinatal morbidity and mortality [32].
●Late-onset FGR (in the absence of congenital anomalies) defines FGR identified at ≥32 weeks of gestation [31]. It is more common than early-onset FGR and it is associated with lower risks for perinatal morbidity and mortality, but neurodevelopment may be impaired [33].
●Small for gestational age (SGA) is defined as a newborn birth weight <10th percentile for gestational age [27]. This definition does not make a distinction among newborns who are constitutionally small and not at risk for additional morbidity from those who are small because of growth-restriction. Of note, not all fetuses classified as FGR during pregnancy will be SGA at birth and not all newborns classified as SGA at birth will be identified as FGR during pregnancy.
RISK FACTORS — Maternal, fetal, and placental factors (table 1) can impact fetal growth potential, and are not necessarily independent. For example, maternal vascular disease can result in placental changes leading to placental insufficiency.
●Placental – Placental insufficiency is the most common risk factor for FGR. Other placental abnormalities, including velamentous cord insertion, circumvallate placenta, and single umbilical artery, have also been associated with FGR.
Prenatally, placental insufficiency cannot be directly measured and is a diagnosis of exclusion. FGR is usually attributed to placental insufficiency when EFW is <10th percentile and other causes of FGR have been excluded (fetal genetic abnormalities, fetal structural anomalies, fetal infections, maternal substance use or use of some medications), particularly if umbilical or maternal uterine artery Doppler velocimetry is abnormal.
●Maternal – Maternal vascular disease (such as chronic hypertension), kidney disease, diabetes, collagen vascular disease, and antiphospholipid syndrome are common risk factors for FGR. Tobacco and substance use, including cocaine, alcohol, and opioids, are modifiable risk factors. Medication exposures, such as certain anti-seizure and chemotherapeutic medications and warfarin, can also negatively impact fetal growth [27].
●Fetal – Fetuses with genetic abnormalities, syndromes, and congenital anomalies are at higher risk for FGR. Fetal infection with malaria, cytomegalovirus, syphilis, rubella, varicella, and toxoplasmosis are responsible for about 5 to 10 percent of cases.
SCREENING
Benefits and harms — Prenatal detection of FGR enables initiation of formal fetal surveillance with the goal of maintaining the pregnancy as long as safely possible while decreasing the risk for adverse outcome or stillbirth. (See "Fetal growth restriction: Pregnancy management and outcome" and "Fetal growth restriction (FGR) and small for gestational age (SGA) newborns".).
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 birth).
Screening strategies — Screening strategies differ among countries, with some using a risk-based approach to select pregnancies for ultrasound assessment of fetal growth whereas others routinely assess fetal growth sonographically in all pregnancies. The optimum strategy is unclear. Regardless of the strategy used, the majority of small for gestational age (SGA) newborns remain undetected prior to birth (ie, FGR was probably present in utero but not diagnosed) [9,34,35]. Indeed, 75 to 80 percent of SGA newborns may not be detected antenatally [35].
In a meta-analysis of randomized trials, compared with selective use, routine ultrasound examination in late pregnancy (after 24 weeks of gestation) did not reduce perinatal mortality (relative risk [RR] 1.01, 95% CI 0.67-1.54), preterm birth (RR 0.96, 95% CI 0.85-1.08), or induction of labor (RR 0.93, 95% CI 0.81-1.07) [36]. Routine use was not clearly harmful as it did not increase cesarean birth rates (RR 1.02, 95% CI 0.97-1.09); however, potential maternal psychological effects and other neonatal outcomes could not be assessed. In another meta-analysis of randomized trials, compared with serial fundal height measurements, routine ultrasound examination in the third trimester did not reduce perinatal death in low-risk pregnancies (0.4 versus 0.3 percent, RR 1.14, 95% CI 0.68-1.89) [37].
Our approach — Our approach to screening for FGR is described below and in the algorithm (algorithm 1). This approach is consistent with several international guidelines, which recommend a risk-based assessment to select pregnancies warranting ultrasound surveillance of fetal growth and using fundal height measurements after 24 weeks in all pregnancies to detect those with a possible lag in fetal growth, which would warrant ultrasound examination [2,27].
●For low-risk pregnancies, if there is a ≥4 cm lag in the fundal height measurement or fundal height cannot be adequately assessed, we perform an ultrasound examination to assess fetal size, determine EFW, assess amniotic fluid volume, and evaluate the placenta.
●For pregnancies with risk factors for FGR, we perform a growth scan to determine EFW and assess amniotic fluid volume as early as 28 weeks. Additional follow-up examinations are performed as frequently as up to every three to four weeks based on assessment of the pregnant individual's risk profile. Scans are not performed at intervals of ≤2 weeks because interobserver and intraobserver variability in fetal biometric measurements in such scans can account for abnormalities in biometric and EFW percentiles; this is less of a problem when the time between scans is at least three weeks.
Maternal history-based approach — A detailed medical and obstetric history is obtained at the first prenatal visit to identify any maternal medical conditions that are known to increase the risk for FGR. Patients with historic risk factors are candidates for ultrasound surveillance of fetal growth. In addition:
●If tobacco or substance use is reported, cessation should be encouraged. (See "Tobacco and nicotine use in pregnancy: Cessation strategies and treatment options" and "Alcohol intake and pregnancy", section on 'Management of screen-positive pregnant persons' and "Substance use during pregnancy: Screening and prenatal care".)
●For individuals at increased risk for preeclampsia, low-dose aspirin prophylaxis should be started prior to 16 weeks of gestation to decrease the risks of preeclampsia and FGR. These data are reviewed separately. (See "Preeclampsia: Prevention", section on 'Low-dose aspirin'.)
Fundal height measurement-based approach — Assessing fundal height is a routine component of prenatal care and is a simple and inexpensive tool to screen for abnormal fetal growth. By 12 weeks of gestation, the uterine fundus can be palpated at the level of the pubic symphysis. At 16 weeks, the fundus is approximately midway between the symphysis and the umbilicus. The fundus reaches the umbilicus at about 20 weeks of gestation. Beyond 24 weeks, the measurement in centimeters (+/- 3 cm) approximates the gestational age in weeks [38]. Therefore, a fundal height measurement ≥4 cm discordant with the expected size for dates is considered a potential marker for FGR and ultrasound examination.
Fundal height is measured using the unmarked side of a tape measure to reduce clinician bias [39,40]. The distance between the upper border of the pubic symphysis to the top of the uterus is recorded. Several factors may impact the fundal height assessment, including obesity, fibroids, bladder filling, and extremes of amniotic fluid volume (oligohydramnios and polyhydramnios) [41,42].
The sensitivity of fundal height to detect FGR ranges from 17 to 86 percent, so it is not a sufficient screening tool in isolation [43-47]. Serial measurements by the same provider plotted on an individualized chart improves performance of fundal height to detect abnormal fetal growth [41,44].
Routine ultrasound screening at 32 and/or 36 weeks — An anatomic survey at 18 to 22 weeks of gestation is standard practice in resource-abundant countries, but ultrasound screening examinations after this point in gestation, although common, are not routinely performed worldwide. In low-risk populations, international guidelines do not advocate routine third-trimester ultrasound screening [48] because it has not been proven to decrease perinatal mortality. In a meta-analysis of randomized trials comparing routine third-trimester ultrasound(s) with serial fundal height measurements, perinatal mortality was similar in both groups (0.4 versus 0.3 percent; RR 1.1, 95% CI 0.68-1.89) [37]. Another meta-analysis of cohort studies found that EFW or AC <3rd percentile at ≥32 weeks of gestation was associated with an increased risk of perinatal complications; however, as standalone parameters they performed poorly in predicting adverse perinatal outcome [49].
Because available evidence is inconclusive and larger trials are needed to improve the precision of these outcome results, practice varies among clinicians, and some perform sonographic screening. If a single third-trimester screening examination is performed, it should be done close to 36 weeks, as ultrasound estimated fetal weight (EFW) <10th percentile at 36 weeks of gestation detects SGA better than a sonogram at 32 weeks [50]. If two screening examinations are to be performed, then it is reasonable to time them for 32 and 36 weeks.
DIAGNOSIS
Criteria — In the United States, the diagnosis of FGR is based on sonographic estimation of fetal weight (EFW) <10th percentile or fetal abdominal circumference (AC) <10th percentile on a population-based or customized growth curve [2,27]. AC performs similarly to EFW for predicting SGA [51,52]. Based on expert consensus, FGR is highly likely in nonanomalous fetuses with EFW or AC <3rd percentile, regardless of gestational age [29,31]. When EFW or AC are between the 3rd and 10th percentile, abnormal Doppler parameters and decreasing growth trajectory of the EFW or AC support the diagnosis of placenta-based pathologic FGR and reduce the likelihood of a constitutionally small fetus.
By comparison, the International Society of Obstetricians and Gynecologists criteria include Doppler parameters for diagnosis of FGR (table 2). In a comparative study, the SMFM-ACOG-AIUM criteria used in the United States had a higher sensitivity for the prediction of SGA (birth weight <10th percentile) than the ISUOG criteria (55 versus 29 percent) but lower specificity (93 versus 98 percent) [53]. Both approaches performed poorly in predicting composite adverse neonatal outcome (sensitivity 10 to 15 percent). Similar findings were reported in a subsequent study comparing SMFM and ISUOG/Delphi criteria for detecting late-onset growth restriction (SGA: sensitivity 32 versus 16 percent and specificity 98.9 versus 99.4 percent; severe neonatal morbidity: sensitivity 8.4 versus 4.9 percent) [54].
Supporting characteristics — Differentiating the constitutionally small from the pathologically small fetus remains a clinical challenge [55]. Making a correct diagnosis of FGR versus constitutional smallness is important because the former is associated with adverse outcome and the latter is not.
●EFW or AC <3rd percentile identifies a group of fetuses at higher risk for adverse perinatal morbidity and stillbirth [12,56]. Even if amniotic fluid and Dopplers are normal, the risk for stillbirth is threefold higher than in fetuses in the 3rd to 5th percentile range and four- to sevenfold higher than those in the 5th to 10th percentile range [56]. In a large retrospective cohort of newborns, the incidence of an umbilical artery pH <7 at birth, intubation, seizures in the first day of life, sepsis, and perinatal death were also significantly higher at <3rd percentile, even with term birth [11]. In another study, neurodevelopment was negatively impacted in children born at <3rd percentile even when Doppler studies were normal [57].
●Oligohydramnios can narrow the differential diagnosis for underlying causes of FGR. Oligohydramnios is presumably due to decreased fetal urination as a result of blood flow redistribution away from the kidneys to more vital organs in the setting of fetal hypoxemia [58,59]. It is associated with adverse outcome when the EFW is <3rd percentile for gestational age [60]. Polyhydramnios in the setting of FGR or structural malformation increases the risk for aneuploidy (particularly trisomy 18) or genetic syndromes [61]. For these cases, genetic counseling and diagnostic testing with chromosomal microarray are advised [2,27,28,61,62]. (See "Oligohydramnios: Etiology, diagnosis, and management in singleton gestations" and "Polyhydramnios: Etiology, diagnosis, and management in singleton gestations".)
●Abnormal Doppler velocimetry of the uterine arteries and fetal vessels (eg, umbilical, middle cerebral, ductus venosus) suggests reduced perfusion of the placental villous vasculature from both the maternal and fetal compartments.
•Uterine arteries – Flow in the uterine arteries increases beginning in the first trimester as remodeling of the spiral arteries allows transition from a high resistance to a high-flow, low-impedance circulation [63]. If this process does not occur normally, then a high-resistance state persists, which can impair placental function [64]. Some guidelines use uterine artery Doppler as an adjunct to screening for FGR [2,27], while others recommend it only for moderate or high-risk individuals in the second trimester [48]. A meta-analysis of 61 mostly cohort studies including over 41,000 patients revealed that second-trimester abnormal uterine artery Doppler pulsatility index with notching of the waveform predicted overall FGR with a likelihood ratio of 9.1 (95% CI 5.0-16.7) and severe FGR with a likelihood ratio of 14.6 (95% CI 7.8-26.3) [65]. However, a subsequent multi-center randomized trial of uterine artery Doppler in an unselected population failed to show either maternal or neonatal benefit [66].
•Fetal vessels – In pregnancies in which a small fetus is diagnosed, abnormal umbilical artery Doppler findings can help to differentiate between the constitutionally small and the pathologically small fetus [60,67]. Although deterioration of fetal Dopplers does not always follow a predictable pattern, appropriate fetal Doppler and biophysical monitoring and intervention can decrease perinatal mortality in these cases [68,69]. Fetal Doppler evaluation (umbilical artery, middle cerebral artery [including the cerebroplacental ratio and umbilicocerebral ratio], ductus venosus) in FGR and pregnancy management based on these findings are reviewed in detail separately. (See "Fetal growth restriction: Evaluation", section on 'Doppler velocimetry' and "Fetal growth restriction: Pregnancy management and outcome", section on 'Fetal surveillance'.)
Doppler changes have been used as the basis of staging systems to describe the severity of FGR, but such systems are not widely used [70,71].
Diagnosis in special populations
Uncertain gestational age — When pregnancy dating is unknown, a single ultrasound examination may not be able to distinguish a fetus that is FGR from an earlier gestational age fetus. In these cases, serial ultrasounds performed at least two weeks apart are required and should include measurement of fetal biometry, assessment of amniotic fluid, and umbilical artery Doppler assessment.
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 there is less daily increase in weight [72]. If interval growth is appropriate and the other parameters are normal, FGR is less likely and outcomes are favorable [73,74]. Poor interval growth, oligohydramnios, or abnormal umbilical artery Dopplers are more likely encountered in cases of FGR [75].
The head circumference to abdominal circumference ratio (HC/AC) decreases linearly throughout pregnancy; a ratio >2 standard deviations (SDs) above the mean for gestational age is considered abnormal and a possible sign of asymmetric FGR. However, this ratio is not independent predictor of adverse pregnancy outcome or childhood growth and development, and an increased HC/AC can be due to causes other than FGR, so it is not useful diagnostically or prognostically [76-79].
Multiple gestation — The growth curve for multiple gestations is similar to singleton pregnancies until approximately 32 weeks when the growth velocity slows [80]. In dichorionic twins, each fetus has an independent risk for FGR based on the risk factors described above (see 'Risk factors' above). Monochorionic twins have a higher risk for FGR based on discordant placental sharing, which 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" and "Society guideline links: Ultrasound imaging in pregnancy".)
SUMMARY AND RECOMMENDATIONS
●Diagnosis – The diagnosis of a small fetus is based on sonographic estimation of fetal weight (EFW) <10th percentile or fetal abdominal circumference (AC) <10th percentile on population-based or customized growth curves. Fetal growth restriction (FGR) is highly likely in nonanomalous well-dated fetuses with EFW or AC <3rd percentile, regardless of gestational age. When EFW or AC are between the 3rd and 10th percentile, supporting characteristics, such as abnormal Doppler parameters and decreasing growth trajectory of the EFW or AC, support the diagnosis of placenta-based pathologic FGR and reduce the likelihood of a constitutionally small fetus. (See 'Definitions' above and 'Criteria' above and 'Supporting characteristics' above.)
●Screening – Our approach to identifying pregnancies with FGR is described in the algorithm (algorithm 1) and aligns with several international guidelines. Pregnancies at high risk of FGR (table 1) are monitored with periodic ultrasound examinations to assess fetal size. Pregnancies not at high risk are monitored with fundal height measurements beginning at 24 weeks to detect those with size less than expected for gestational age, which would warrant ultrasound examination. (See 'Our approach' above.)
●Benefits and harms – Prenatal detection of FGR enables initiation of formal fetal surveillance with the goal to maintain the pregnancy as long as safely possible while decreasing the risk for adverse outcome or stillbirth. 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 birth). (See 'Benefits and harms' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Michael Y Divon, MD, who contributed to earlier versions of this topic review.
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