INTRODUCTION — Fetal growth restriction (FGR) is broadly defined as an estimated fetal weight (EFW) or abdominal circumference (AC) <10th percentile for gestational age. Severe FGR is generally defined as an EFW or AC <3rd percentile for gestational age; the presence of fetal umbilical artery (UA) Doppler abnormalities also suggests that FGR is severe. However, sonographic criteria for diagnosis of FGR vary (table 1) [1-3]. None of these criteria is ideal for identification of FGR as all have poor performance for predicting adverse neonatal outcome . (See "Fetal growth restriction: Screening and diagnosis", section on 'Diagnosis'.)
Identification of FGR is an integral component of prenatal care as it is a leading cause of perinatal morbidity and mortality . When FGR is suspected, the obstetric provider needs to confirm the suspected diagnosis, determine the probable cause, assess the severity, counsel the parents, closely monitor fetal growth and well-being for the remainder of the pregnancy, and determine the optimal time for and route of birth. Although FGR is not a homogeneous entity, uteroplacental insufficiency with suboptimal fetal nutrition and hypoperfusion is a common pathway to many forms of FGR. It can be present in patients with pregnancy-associated hypertension, chronic hypertension, chronic kidney disease, maternal or fetal infection, diabetes with vasculopathy, and fetal aneuploidy. In these cases, the fetus is closely monitored to identify those who are at highest risk of perinatal demise and thus may benefit from early delivery.
This topic will discuss the evaluation of FGR in singleton pregnancies. Pregnancy management and outcome are reviewed separately. (See "Fetal growth restriction: Pregnancy management and outcome".)
FGR in twin pregnancies is also reviewed separately. (See "Twin pregnancy: Routine prenatal care", section on 'Screening for fetal growth restriction and discordance' and "Selective fetal growth restriction in monochorionic twin pregnancies".)
INITIAL EVALUATION — The diagnosis of FGR is established sonographically (see "Fetal growth restriction: Screening and diagnosis"). The pregnancy is then evaluated to determine whether fetal growth is impaired as a result of maternal, fetal, or placental processes (table 2). However, this determination cannot always be made antenatally, despite the following evaluation. When no maternal and/or fetal predisposing factors are found, FGR may be termed idiopathic or isolated [6,7].
Size percentile — Fetuses <3rd percentile are at greatest risk of adverse outcome. Most fetuses with EFW or AC between the 5th and 10th percentiles are constitutionally small and thus have normal neonatal outcomes [8,9]. However, they still need to be monitored closely because a proportion are FGR and at increased risk of adverse outcome.
●In a population-based retrospective cohort study composed of all singleton term pregnancies in Scotland between 1992 and 2008, the overall association between birth weight percentile and risk of perinatal death had a reverse J-shaped distribution . Birth weight <3rd percentile had the highest relative risk of antepartum stillbirth and the absolute risk of stillbirth in this group was approximately 1 in 100.
●In a retrospective study of 834 prenatally suspected FGR cases, composite neonatal morbidity at <5th percentile was 29 percent versus 15 percent at the 5th to 9th percentile (adjusted odds ratio 2.22, 95% CI 1.34-3.67) .
●In the Prospective Observational Trial to Optimize Pediatric Health (PORTO), which included over 1100 nonanomalous fetuses with EFW <10th percentile at 24+0 to 36+6 weeks of gestation, only 2 percent of those at the 3rd to 10th percentile (5 of 254) experienced adverse perinatal outcome, while 6.2 percent of those <3rd percentile (51 of 826) had an adverse outcome and all eight mortalities were in this group .
Maternal history and physical examination — The medical and obstetric history and physical examination help to identify maternal factors that have been associated with restricted fetal growth (table 2).
Maternal characteristics have a major influence on fetal growth potential. For example, when race/ethnicity was taken into account, the 5th percentiles for White, Hispanic, Black, and Asian populations at 39 weeks of gestation were 2790, 2633, 2622, and 2621 grams, respectively, in a prospective study of over 2300 healthy individuals with low-risk, singleton pregnancies from 12 medical centers in the United States . Using biometric standards derived solely from the group of fetuses from the White population, as many as 15 percent of the fetuses from other groups would have been classified as growth restricted (<5th percentile).
Although pregnancy-associated hypertensive disorders are commonly considered causal factors, a study by the National Institute of Child Health and Human Development (NICHD) found that only preeclampsia with severe features, particularly with onset <34 weeks of gestation, was associated with a significant and consistent impairment in fetal growth compared with normotensive pregnancies . Growth impairment was observed as early as 22 to 23 weeks of gestation and could precede the characteristic maternal findings defining the disorder.
Fetal anatomic survey — A detailed fetal anatomic survey should be performed in all cases since approximately 10 percent of FGR is associated with congenital anomalies  and 20 to 60 percent of anomalous infants are small for gestational age . These anomalies include omphalocele, gastroschisis, diaphragmatic hernia, skeletal dysplasia, some congenital heart abnormalities, and rarely congenital portosystemic shunts . Although omphalocele and gastroschisis can be associated with FGR, the AC is distorted by the anomaly in these cases, limiting the utility of biometric measurements for diagnosis of FGR.
A fetal echocardiogram is indicated if there is uncertainty about normal cardiac development on a detailed ultrasound examination.
Selective work-up for genetic abnormalities
●Candidates for genetic studies – We suggest offering fetal genetic testing to patients in any of the following settings:
•FGR before 32 weeks in the absence of an identifiable nongenetic cause of the growth restriction. After 32 weeks, fetal genetic testing is typically not performed when anatomy is normal since the risk of aneuploidy is low [16-18].
•FGR with major fetal structural abnormalities or ultrasound markers associated with an increased risk of aneuploidy, such as a thickened nuchal fold.
•FGR with polyhydramnios.
•Ultrasound findings suggestive of a triploid pregnancy.
This approach generally aligns with that of the American College of Obstetricians and Gynecologists (ACOG), which suggests genetic counseling and offering diagnostic testing for patients with a diagnosis of FGR before 32 weeks or FGR in combination with polyhydramnios or fetal malformation .
●Testing modality – Genetic counseling is useful in helping patients understand the benefits, risks, and limitations of the various genetic testing modalities, including whether to begin with a noninvasive screening test (cell-free DNA [cfDNA]) or a diagnostic test that requires amniocentesis, and when to pursue advanced genetic testing (exome and whole genome sequencing). In the author's practice, patients with nonanomalous FGR are counseled by a maternal-fetal medicine specialist and a genetic counselor. If the patient chooses to undergo amniocentesis, the author favors chromosomal microarray analysis. If the microarray analysis is nondiagnostic, performing additional genetic testing is controversial; however, exome and whole genome sequencing are promising approaches.
Genetic testing modalities include:
•Cell-free DNA of maternal blood – Cell-free DNA (cfDNA) is a screening test for trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), trisomy 13 (Patau syndrome), and selected sex chromosome aneuploidies. It has the advantage of being noninvasive, but it is not diagnostic. Test performance is reviewed separately. (See "Prenatal screening for common aneuploidies using cell-free DNA".)
•Microarray or conventional karyotype – Microarray or conventional karyotype is performed on cells in amniotic fluid obtained by amniocentesis. Compared with a conventional karyotype, microarray analysis has a higher diagnostic yield as it detects both aneuploidy and microdeletions and duplications, thus it can improve the detection of genetic anomalies, especially in fetuses with nonanomalous FGR [19,20]. In a meta-analysis to estimate the incremental yield of microarray analysis over conventional karyotyping in FGR, microarray had a 4 percent (95% CI 1-6) incremental yield in nonanomalous FGR and a 10 percent (95% CI 6-14) incremental yield in FGR with associated anomalies . The most common pathogenic copy number variants in growth restricted fetuses were 22q11.1 duplication, Xp22.3 deletion, and 7q11.23 deletion. (See "Prenatal diagnosis of chromosomal imbalance: Chromosomal microarray".)
Microarray or conventional karyotype can also be performed on trophoblast obtained by chorionic villus sampling (CVS); however, this test is typically restricted to first-trimester pregnancies and thus before a diagnosis of FGR is typically made. Although CVS will detect confined placental mosaicism (CPM), we do not perform placental biopsy in the second or third trimester to identify this abnormality antepartum because antenatal diagnosis of CPM would not change pregnancy management and the procedure is associated with a small risk of pregnancy complications.
•Exome and whole genome sequencing – The appropriate use of exome and whole genome sequencing in FGR without anatomic abnormalities is under investigation. In a prospective study of 19 small-for-gestational-age newborns without a known cause and with normal karyotype and microarray, three were subsequently found to have a genetic cause with whole genome sequencing .
●Genetic causes of FGR – Genetic causes of FGR are listed in the table (table 3) and selectively discussed in more detail below:
•Aneuploidy – In a systematic review, the risk of chromosomal abnormalities in apparently isolated FGR was 6.4 percent . Trisomy 21 and 18 accounted for five and three cases, respectively, of the 22 cases with numeric abnormalities. However, the authors emphasized that the small number of cases and low quality of evidence limited an accurate estimate for chromosomal abnormalities in pregnancies with isolated FGR. Others have also reported an increased risk of FGR in trisomy 21 pregnancies without severe structural anomalies  and with trisomy 13 .
Triploidy of paternal origin (diandric) is characterized by symmetric FGR with associated structural abnormalities in most cases and an enlarged placenta with hydropic and cystic changes (often a partial mole) [17,18]. Triploidy of maternal origin (digynic) is nonmolar and characterized by asymmetric FGR and a small placenta; holoprosencephaly may be present. Both types of triploidy may have oligohydramnios and abnormal Doppler velocimetry . Fetuses with digynic triploidy are more likely to survive to the second trimester than those with diandric triploidy.
•Monogenic disorders – Fetuses with FGR related to monogenic disorders (eg, Cornelia de Lange, Smith-Lemli-Opitz, Meier-Gorlin, Noonan syndromes ) often have other findings, including thickened nuchal fold, congenital heart disease, and limb reduction defects. The pediatric outcome is often due to the abnormalities present in each case, and neurodevelopment may be either normal or show moderate to severe intellectual disability.
•Confined placental mosaicism – CPM increases the risk for FGR at least three-fold  and is present in about 10 percent of cases with unexplained FGR [26,27]. CPM of chromosomes 2, 7-10, 13-18, 21, and 22 is disproportionately found in FGR fetuses. CPM for trisomy 16 deserves special consideration as it is estimated to complicate approximately 1 percent of all pregnancies and is associated with FGR in 43 to 58 percent of cases . It has also been associated with fetal malformations, preeclampsia, and preterm birth.
•Uniparental disomy – Genes related to fetal growth are differentially expressed depending on the parent of origin. Imprinted genes control placental development, nutrient exchange, and growth rate. Uniparental disomy is rare and can lead to dysregulation of imprinted genes. The most common of these is uniparental disomy of chromosome 7 leading to Silver-Russell syndrome. Other causes are listed in the table (table 3).
•Epigenetic changes – Although epigenetic changes (modification of gene expression rather than differences in the DNA coding sequence) are emerging as key regulators of placental function, methods and utility of clinical testing for these changes as a cause of FGR remain investigational. Many cases of Silver-Russell syndrome are due to epigenetic alterations involving hypomethylation of an imprinting control region that regulates expression of the insulin-like growth factor 2 gene or others on 11p15.5 chromosome.
Selective work-up for infection — The author obtains serology studies for infection when FGR is associated with sonographic markers of fetal infection (echogenicity and calcification of the brain and/or liver, hydrops) or when a careful maternal history and physical examination suggest the possibility of maternal infection and vertical transmission. He does not perform routine TORCH serology in the evaluation of isolated FGR. If the patient chooses to have diagnostic fetal infection testing for isolated FGR, he performs amniocentesis for polymerase chain reaction (PCR) of amniotic fluid for cytomegalovirus (CMV). In patients who live in or travel to areas where malaria is endemic, malaria should be considered a possible etiology of FGR and excluded (see "Malaria in pregnancy: Epidemiology, clinical manifestations, diagnosis, and outcome"). Similarly, in patients at increased risk for Zika virus infection, congenital Zika virus infection should be considered a possible etiology of FGR and excluded (see "Zika virus infection: Evaluation and management of pregnant patients"). Screening for syphilis one or more times is a routine prenatal test recommended for all pregnant patients. In a literature review of 161 cases of congenital syphilis, 23 (14 percent) had FGR. (See "Syphilis in pregnancy", section on 'Candidates and timing of initial and repeat screening'.)
Although infections such as CMV, toxoplasmosis, rubella, varicella, and herpes simplex may be associated with FGR (refer to individual topic reviews on specific fetal infections during pregnancy for a description of the ultrasound findings), use of maternal serology should be limited because, when positive, the time of occurrence of the primary infection is often difficult to determine. This may lead to unnecessary invasive procedures with associated parental anxiety and cost. Due to its low yield, the Society for Maternal-Fetal Medicine recommends against TORCH serology for isolated FGR and recommends PCR of amniotic fluid for CMV in patients with unexplained FGR who elect to have diagnostic testing . In a systematic review including 2538 pregnancies in eight studies, 496 TORCH serologies were performed in patients with FGR (EFW <10th percentile) . Of this group, 12 were positive (2.4 percent, 95% CI 1.4-4.2%) and 10 congenital infections were detected (eight CMV, two parvovirus B19), but only 2 of the 10 fetuses had isolated FGR (CMV infection was found in both cases). The studies included in this review did not differentiate between early and late FGR (ie, onset <32 versus ≥32 weeks) and there were no cases of rubella or herpes simplex virus.
Maternal COVID-19 does not appear to be associated with an increased risk of FGR [29,30]. However, data on perinatal outcomes when the infection is acquired in early pregnancy are limited, and any condition that results in prolonged maternal hypoxia or placental dysfunction places the fetus at risk for growth restriction. (See "The placental pathology report", section on 'Chronic histiocytic intervillositis'.)
●Routinely testing for antiphospholipid antibodies is not recommended as there is insufficient evidence to support evaluating all pregnancies with FGR for antiphospholipid antibody syndrome (APS). Early-onset placental insufficiency (eg, FGR) with birth before 34 weeks of gestation is one of the clinical criteria for the diagnosis of APS by expert consensus (table 4) . Testing for antiphospholipid antibodies in patients with this obstetric history has been suggested for those who also manifest livedo, valvular heart disease, neurologic findings such as cognitive deficits and white matter lesions, a systemic autoimmune disease (especially systemic lupus erythematosus) with appropriate clinical symptoms, and/or laboratory abnormalities such as otherwise unexplained mild thrombocytopenia, prolongation of the activated partial thromboplastin time (aPTT), or a history of a false-positive serologic test for syphilis (Venereal Disease Research Laboratory [VDRL] or rapid plasma reagin [RPR] tests). (See "Diagnosis of antiphospholipid syndrome", section on 'When to suspect the diagnosis' and "Diagnosis of antiphospholipid syndrome", section on 'Diagnostic evaluation' and "Antiphospholipid syndrome: Obstetric implications and management in pregnancy", section on 'Adverse pregnancy outcomes defining APS'.)
●Assessment for inherited thrombophilic disorders is not recommended as evidence of an association between the inherited thrombophilias and FGR is weak. (See "Inherited thrombophilias in pregnancy", section on 'Adverse pregnancy outcome risk'.)
SUBSEQUENT EVALUATION — After the initial evaluation, additional assessments are performed over time to help distinguish the fetus at increased risk of adverse outcome from the constitutionally small fetus or the fetus who is minimally impacted from a placenta-mediated disorder or other pathologic factors that impair fetal growth and at low risk of adverse outcome. The modalities are described below; our approach to obtaining these assessments and managing the pregnancy based on the findings is provided separately. (See "Fetal growth restriction: Pregnancy management and outcome".)
Fetal weight — Fetal weight is calculated using various published equations and formulae. Most clinicians use the Hadlock formula . The computed EFW is then compared with Hadlock standards for fetal weight across gestation or plotted on a population-based or customized growth curve . The rate of adverse perinatal outcomes are inversely related to the percentile .
Doppler velocimetry — The hemodynamic physiology of FGR is the basis for the use of Doppler ultrasound to monitor and manage affected pregnancies. The classic progressive sequence of Doppler changes in the peripheral and central circulatory systems leading to fetal compromise or death in FGR are shown in the figure (figure 1) but other patterns of Doppler deterioration also exist [6,35-38]. This sequence is most likely to progress quickly (within days) when the onset of FGR is earlier in gestation and with increasing severity of placental insufficiency . Doppler abnormalities in late gestational FGR may progress slowly (within weeks) or not at all or along a different pathway . The reason is that FGR is not a homogeneous entity and different phenotypes of FGR behave differently. For example, FGR associated with preeclampsia with severe features may have a different clinical course from idiopathic FGR .
The following figures (figure 2 and figure 3) compare the Doppler changes observed from the time of initial diagnosis of FGR until delivery or fetal demise in a series of pregnancies with idiopathic FGR versus those with FGR associated with preeclampsia diagnosed at <32 weeks of gestation. It is important to emphasize that not all fetal vessels reported in the figures are used in current clinical practice. (See "Fetal growth restriction: Pregnancy management and outcome", section on 'Doppler ultrasonography, nonstress test/cardiotocography, and biophysical profile'.)
Umbilical artery Doppler — UA Doppler is the primary surveillance tool for monitoring pregnancies with FGR [1,3,19,40]. UA diastolic flow normally increases with advancing gestational age (waveform 1). UA indices become abnormal when 30 percent of the placental villous vasculature is damaged by embolization . When 60 to 70 percent of the placental villous vasculature is obliterated, flow in the UA can become absent or even reversed at the end of the cardiac cycle (waveform 2) .
The most common UA Doppler indices used in clinical obstetric practice are:
●Pulsatility index (PI = peak systolic velocity - end-diastolic velocity/time-averaged maximum velocity) 
●Resistance index (RI = peak systolic velocity – end-diastolic velocity/peak systolic velocity) 
●S/D ratio: Peak systolic velocity/end-diastolic velocity 
Reference ranges for the three UA indices have been reported in many studies, including a longitudinal study . The PI is preferred because it gives a better estimate of the characteristics of the waveform than the RI or S/D ratio . A value above the 95th percentile for gestational age is considered abnormal.
The severity of UA Doppler abnormalities correlates with prognosis: Reversed diastolic flow is associated with fivefold higher perinatal mortality compared with absent flow . Numerous randomized trials and well-designed observational studies have established that monitoring UA Doppler can significantly reduce perinatal death by prompting early delivery when it is abnormal. In addition, a normal Doppler is infrequently associated with significant perinatal morbidity or mortality and is strong evidence of fetal well-being; thus, this finding provides support for delaying delivery of preterm gestations when it is important to gain further fetal maturity.
●In a systematic review of 19 trials comparing the use of mostly UA Doppler with no Doppler in over 10,000 high-risk pregnancies, Doppler use reduced perinatal deaths (1.2 versus 1.7 percent; risk ratio [RR] 0.71, 95% CI 0.52-0.98; number needed to treat 203), labor induction (RR 0.89, 95% CI 0.80-0.99) and cesarean births (RR 0.90, 95% CI 0.84-0.97) .
●In the Prospective Observational Trial to Optimize Pediatric Health in FGR (PORTO) study, FGR with normal UA Doppler was associated with less perinatal mortality than FGR with abnormal Doppler (2 of 698 [0.3 percent] versus 6 of 418 [1.4 percent]) and a lower rate of overall adverse outcome (9 of 698 [1.3 percent] versus 48 of 418 [11.5 percent]) [8,50]. In addition, the combination of EFW <3rd percentile and abnormal UA Doppler was a strong and consistent predictor of adverse outcome: 16.7 percent of these fetuses developed intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, or death. Abnormal UA Doppler was defined as a pulsatility index (PI) >95th percentile or absent/reversed end-diastolic flow.
A detailed discussion of Doppler interrogation of the UA, including performance of the test, is available separately. (See "Doppler ultrasound of the umbilical artery for fetal surveillance in singleton pregnancies".)
Middle cerebral artery pulsatility index — In uncomplicated pregnancies, vascular resistance of the fetal brain changes with advancing gestation, thus the middle cerebral artery (MCA) PI is low at early gestational ages (<20 weeks), then gradually increases, before gradually decreasing in the third trimester [51,52]. However, in fetuses such as those with FGR experiencing progressive hypoxemia, cerebral blood flow increases to compensate for the decrease in available oxygen (brain-sparing effect) (waveform 3) , which results in a reduction in MCA PI [6,7,35,37,38]. Subsequent normalization of the MCA PI may occur and is considered an ominous sign because it indicates the loss of brain-sparing .
The MCA PI can be the first parameter to become abnormal in late FGR , followed by the UA PI. An abnormal MCA PI is found in approximately 20 percent of FGR cases with normal UA PI in the third trimester [56,57] and associated with a higher incidence of suboptimal neurodevelopmental outcome at two years of age compared with a normal MCA PI . In a study of 856 FGR cases between 32 and 36.6 weeks, an abnormal MCA PI (<5th percentile for gestational age) had higher relative risk of a composite adverse outcome compared with the UA PI . Two fetuses died; in both cases, UA PI was normal while MCA PI was abnormal.
MCA Doppler results can be used to calculate two ratios sometimes used in the evaluation of FGR. (See 'Cerebroplacental ratio' below and 'Umbilicocerebral ratio' below.)
Ductus venosus Doppler — Normal flow in the fetal ductus venous (DV) is forward and uniform . With progressively increasing UA resistance in FGR, fetal cardiac performance becomes impaired and atrial pressure increases, resulting in reduced diastolic flow in the DV a-wave. With progression of the severity of FGR, and late in the course of the disorder, the a-wave becomes absent or reversed (waveform 4) [6,7,35,37,38]. Absent or reversed DV a-wave is considered a sign of impending acidemia and fetal demise. It has overall sensitivity of 65 percent and specificity of 95 percent for fetal pH <7.20 . The time from detection of absent or reversed DV a-wave to delivery or fetal demise is variable, and not all very preterm FGR fetuses with this finding are acidemic . Neither neonatal death nor neonatal morbidity are predicted by its duration .
Absent or reversed a-wave is uncommon, occurs more often in early that late FGR, and typically is seen after reversed flow in the UA has been observed.
Biophysical profile and nonstress test/cardiotocography — Both the nonstress test (NST; also called cardiotocography [CTG]) with amniotic fluid volume determination and the biophysical profile (BPP) are used to monitor fetal status as these tests evaluate both acute and chronic fetal physiologic parameters [19,40]. The tests are relatively easy to perform and are initiated at a gestational age at which an abnormal finding would trigger intervention. The frequency of testing is determined by UA Doppler results and amniotic fluid volume. Normal results in conjunction with normal UA Doppler velocimetry has been associated with improved outcomes in pregnancies with FGR. (See "Fetal growth restriction: Pregnancy management and outcome", section on 'Doppler ultrasonography, nonstress test/cardiotocography, and biophysical profile'.)
The rationale for including a BPP in FGR management is based on its superior reflection of current fetal acid-base balance, which is independent of fetal heart rate testing and multivessel Doppler . It is important to note that the BPP is not used in many countries outside of the United States and the use of computerized cardiotocography (cCTG) rather than conventional CTG for fetal heart rate monitoring and interpretation is used in many of these countries . Specific concerns about the BPP in FGR surveillance are based on a Cochrane review that concluded that there is insufficient evidence from randomized trials to support the use of BPP as a test of fetal well-being in high-risk pregnancies ; however, the analysis mainly included high-risk pregnancies with conditions other than FGR and did not assess acidemia and stillbirth rates in relation to surveillance strategy. In an observational study specifically evaluating use of the BPP in managing early severe FGR (<1000 g), a normal BPP score did not predict the outcome in the next 24 hours of this subgroup of FGR pregnancies , underscoring the importance of using multiple modalities for fetal surveillance and frequent (eg, three times daily) testing.
Similar to the BPP, there has been no randomized trial of the NST in FGR management and no study showing that the NST is superior to the BPP (or vice versa) for the management of FGR. Between 30 and 70 percent of cases of FGR with a nonreactive NST require a BPP to verify fetal well-being. The BPP score is abnormal in 8 to 27 percent of these cases and identifies the need for delivery, which was not suspected by Doppler findings .
Growth velocity — The diagnosis of FGR on a single ultrasound based on an EFW <5th percentile in a well-dated pregnancy, oligohydramnios, and abnormal Doppler indices does not require serial scans for confirmation; however, assessing growth velocity (trajectory) has the potential to assist in the diagnosis of less severe forms of FGR not captured by current diagnostic criteria [2,66-72]. A normal growth velocity (ie, parallel to the growth curve of fetuses with EFW or AC >10th percentile) appears to be predictive of a favorable outcome, while an abnormal growth velocity (a percentile drop between consecutive ultrasound scans of >50 percentiles in EFW or AC [eg, from the 75th percentile to the 20th percentile]) appears to predict perinatal complications (eg, preterm birth, preeclampsia, neonatal morbidity).
The author does not routinely calculate growth velocity as studies have not established that determination of growth velocity substantially improves prediction of birthweight and perinatal outcome (morbidity and mortality) compared with EFW alone. Routine fetal growth velocity assessment is not endorsed by the American College of Obstetrics and Gynecology, Society for Maternal-Fetal Medicine, and American Institute of Ultrasound in Medicine (AIUM) for management of pregnancies affected by FGR [1,19] .
Cerebroplacental ratio — The cerebroplacental ratio (CPR) is the MCA PI divided by UA PI . The CPR reflects both the placental status and fetal response and thus may be a sensitive Doppler index for predicting perinatal outcome . In late-onset FGR, reduction in the CPR may be the only Doppler change present . However, the clinical value of this ratio has not been established, in part because studies have used different threshold values for predicting adverse outcome (CPR <1, <1.05, ≤1.08, <5th percentile) [76-83].
More data are needed to determine whether CPR should be used in clinical practice to monitor FGR.
Umbilicocerebral ratio — The umbilicocerebral ratio (UCR) is the MCA PI divided by UA PI. As fetal Doppler changes become increasingly abnormal with lower MCA and higher UA impedance, CPR tends toward zero whereas the UCR tends toward infinity . The UCR may allow for better differentiation of Doppler abnormalities than the CPR; however, the clinical value of this ratio has not been established.
More data are needed to determine whether UCR should be used in clinical practice to monitor FGR. A randomized trial is underway in the Netherlands to compare outcomes of immediate induction versus expectant management of FGR with abnormal UCR (defined as >0.8) .
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
●Overview – Identification of fetal growth restriction (FGR) is an integral component of prenatal care as it is a leading cause of perinatal morbidity and mortality. When FGR is suspected, the obstetric provider needs to confirm the suspected diagnosis, determine the probable cause, assess the severity, counsel the parents, closely monitor fetal growth and well-being for the remainder of the pregnancy, and determine the optimal time for and route of birth. Although FGR is not a homogeneous entity, uteroplacental insufficiency with suboptimal fetal nutrition and hypoperfusion is a common pathway to many forms of FGR. (See 'Introduction' above.)
●Initial evaluation – Sonographic criteria for diagnosis of FGR vary (table 1). After diagnosis of FGR, the pregnancy is evaluated to determine whether fetal growth is impaired as a result of maternal, fetal, or placental processes (table 2). However, this determination cannot always be made antenatally.
•Percentile – Fetuses <3rd percentile are at greatest risk of adverse outcome. Most fetuses with estimated fetal weight (EFW) or abdominal circumference (AC) between the 5th and 10th percentiles are constitutionally small and thus have normal neonatal outcomes. However, they still need to be monitored closely because a proportion of these fetuses are FGR and at increased risk of adverse outcome. (See 'Size percentile' above.)
•History and physical examination – The medical and obstetric history and physical examination help to assess for maternal factors that have been associated with FGR. (See 'Maternal history and physical examination' above.)
•Fetal anatomic survey – A detailed fetal anatomic survey is performed in all cases since approximately 10 percent of FGR is accompanied by congenital anomalies and 20 to 60 percent of anomalous infants are small for gestational age. (See 'Fetal anatomic survey' above.)
•Genetic testing – We offer fetal genetic diagnostic tests to patients in any of the following settings (See 'Selective work-up for genetic abnormalities' above.):
-FGR without a known cause diagnosed before 32 weeks. After 32 weeks, we do not screen for fetal genetic abnormalities if anatomy is normal since the risk of aneuploidy is more common early in gestation and the yield would be low.
-FGR with major fetal structural abnormalities or ultrasound markers associated with an increased risk of aneuploidy, such as a thickened nuchal fold.
-FGR with polyhydramnios.
-Ultrasound findings suggestive of a triploid pregnancy.
Issues to consider are use of a noninvasive screening test (cell-free DNA) or a diagnostic test (microarray or conventional karyotype) that requires amniocentesis, and when to pursue advanced genetic testing (exome or whole genome sequencing).
•Laboratory testing – We obtain serology studies for infection when FGR is associated with sonographic markers of fetal infection (echogenicity and calcification of the brain and/or liver, hydrops) or when a careful maternal history and physical examination suggest the possibility of maternal infection and vertical transmission. We do not perform routine TORCH serology in the evaluation of isolated FGR. (See 'Selective work-up for infection' above.)
●Subsequent evaluation – After the initial evaluation, periodic assessment of fetal weight and Doppler interrogation of the umbilical artery (UA) are performed to distinguish the fetus at increased risk of adverse outcome from the constitutionally small fetus or a fetus that is minimally impacted from uteroplacental insufficiency or other pathologic factors that impair fetal growth and at low risk of adverse outcome. (See 'Subsequent evaluation' above and "Fetal growth restriction: Pregnancy management and outcome".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Robert Resnik, MD, who contributed to an earlier version of this topic review.
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55 : Clinical Opinion: The diagnosis and management of suspected fetal growth restriction: an evidence-based approach.
56 : Neurodevelopmental outcome in 2-year-old infants who were small-for-gestational age term fetuses with cerebral blood flow redistribution.
57 : Changes in myocardial performance index and aortic isthmus and ductus venosus Doppler in term, small-for-gestational age fetuses with normal umbilical artery pulsatility index.
58 : Fetal cerebral Doppler changes and outcome in late preterm fetal growth restriction: prospective cohort study.
60 : Qualitative venous Doppler waveform analysis improves prediction of critical perinatal outcomes in premature growth-restricted fetuses.
62 : Duration of persistent abnormal ductus venosus flow and its impact on perinatal outcome in fetal growth restriction.
65 : Biophysical profile in the treatment of intrauterine growth-restricted fetuses who weigh<1000 g.
68 : Evaluation of intrauterine growth retardation in the fetus and neonate: are simple-minded methods good enough?
72 : Unified standard for fetal growth velocity: the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies.
74 : Cerebral and umbilical arterial blood flow velocity waveforms in normal and growth-retarded pregnancies.
75 : Longitudinal changes in uterine, umbilical and fetal cerebral Doppler indices in late-onset small-for-gestational age fetuses.
77 : Exploration of the fetal cerebral blood flow by duplex Doppler--linear array system in normal and pathological pregnancies.
78 : Predictive accuracy of cerebroplacental ratio for adverse perinatal and neurodevelopmental outcomes in suspected fetal growth restriction: systematic review and meta-analysis.
79 : Prognostic accuracy of cerebroplacental ratio and middle cerebral artery Doppler for adverse perinatal outcome: systematic review and meta-analysis.
80 : Routine assessment of cerebroplacental ratio at 35-37 weeks' gestation in the prediction of adverse perinatal outcome.
81 : Cerebroplacental ratio in predicting adverse perinatal outcome: a meta-analysis of individual participant data.
82 : The role of brain sparing in the prediction of adverse outcomes in intrauterine growth restriction: results of the multicenter PORTO Study.
83 : An abnormal cerebroplacental ratio (CPR) is predictive of early childhood delayed neurodevelopment in the setting of fetal growth restriction.
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