Guideline No. 442: Fetal Growth Restriction: Screening, Diagnosis, and Management in Singleton Pregnancies

Abstract

ObjectiveFetal growth restriction is a common obstetrical complication that affects up to 10% of pregnancies in the general population and is most commonly due to underlying placental diseases. The purpose of this guideline is to provide summary statements and recommendations to support a clinical framework for effective screening, diagnosis, and management of pregnancies that are either at risk of or affected by fetal growth restriction. Target PopulationAll pregnant patients with a singleton pregnancy. Benefits, harms, and costsImplementation of the recommendations in this guideline should increase clinician competency to detect fetal growth restriction and provide appropriate interventions. EvidencePublished literature in English was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library through to September 2022 using appropriate controlled vocabulary via MeSH terms (fetal growth retardation and small for gestational age) and key words (fetal growth, restriction, growth retardation, IUGR, FGR, low birth weight, small for gestational age, Doppler, placenta, pathology). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Grey literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Validation MethodsThe authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Table A1 for definitions and Table A2 for interpretations of strong and conditional [weak] recommendations). Intended AudienceObstetricians, family physicians, nurses, midwives, maternal-fetal medicine specialists, radiologists, and other health care providers who care for pregnant patients. Tweetable AbstractUpdated guidelines on screening, diagnosis, and management of pregnancies at risk of or affected by FGR. SUMMARY STATEMENTS1.It is important for clinicians to understand the difference between fetal growth restriction and small for gestational age because fetal growth restriction is a risk factor for perinatal morbidity and mortality, while small for gestational age is not (high).2.Small-for-gestational age refers either to a fetus with an ultrasound-derived abdominal circumference or estimated fetal weight below the 10th percentile, as plotted on an appropriate reference chart, or to an infant with birth weight below the 10th percentile, as plotted on an appropriate reference chart (high).3.Fetal growth restriction describes fetal growth does not follow a normal trajectory of growth because of one or more underlying pathological conditions and is broadly categorized as either a rare early-onset disease (prevalence 0.5%–1%) prior to 32 weeks gestation, or a more common late-onset disease (prevalence 5%–10%) when diagnosed at 32 weeks and beyond (moderate).4.The Delphi consensus ultrasound-based criteria should be used to make a diagnosis of fetal growth restriction. These vary by gestational age, and comprise measures of fetal size, fetal growth, and abnormalities of umbilical, uterine, and middle cerebral artery Doppler (moderate).5.Early-onset fetal growth restriction is diagnosed before 32 weeks gestation. At least 1 of the following 3 criteria should be present: (1) an abdominal circumference or estimated fetal weight below the 3rd percentile; (2) late changes in the umbilical artery Doppler assessment (i.e., absent or reversed end-diastolic velocity); or (3) an fetal abdominal circumference or estimated fetal weight below the 10th percentile accompanied by abnormal uterine artery Doppler study (mean pulsatility index >95th percentile) or abnormal umbilical artery Doppler study (pulsatility index >95th percentile) (moderate).6.Late-onset fetal growth restriction is diagnosed at or after 32 weeks gestation by either an abdominal circumference or estimated fetal weight below the 3rd percentile alone or at least 2 of the following 3 criteria: (1) an abdominal circumference or estimated fetal weight below the 10th percentile; (2) an abdominal circumference or estimated fetal weight crossing 2 quartiles; or (3) an abnormal Doppler finding, defined as an umbilical artery Doppler pulsatility index above the 95th percentile or a cerebro-placental ratio below the 5th percentile (moderate).7.In the first trimester, multimodal screening for fetal growth restriction is substantially more effective than clinical risk factor-based screening; however, multimodal screening is not presently recommended because of the logistical challenges to implementation in Canada (moderate).8.In the second trimester, a combination of ultrasound observations (made at the fetal anatomical ultrasound scan) may be useful for identifying pregnancies that are developing early-onset fetal growth restriction. These ultrasound features include: fetal biometry measurements more than 1 week behind gestational age, short femurs, echogenic bowel, a 2-vessel cord, and a marginal or velamentous placental cord insertion. (moderate).9.In the second and third trimesters, neither uterine artery nor umbilical artery Doppler assessments are effective in predicting fetal growth restriction in low-risk pregnancies (high).10.Measurement of circulating maternal placental growth factor in either the second or third trimester is not effective in predicting fetal growth restriction in low-risk pregnancies (moderate).11.Routine symphysis–fundal height measurement has moderate sensitivity and high specificity in detecting fetal growth restriction and is an acceptable approach in clinically low-risk patients with a normal body mass index. Customization of the symphysis–fundal height chart for individual maternal characteristics and previous pregnancy outcomes may improve its effectiveness. Ultrasonography is more accurate than symphysis–fundal height measurement for the detection of fetal growth restriction in patients with a body mass index >35 kg/m2, polyhydramnios, or large fibroids (moderate).12.Umbilical artery Doppler waveforms are typically abnormal in placenta-mediated early-onset fetal growth restriction and typically normal in placenta-mediated late-onset fetal growth restriction. Umbilical artery Doppler findings may be abnormal when fetal growth restriction is due to aneuploidy (e.g., trisomy 18, trisomy 21, and triploidy) or other intrinsic fetal diagnoses (high). RECOMMENDATIONSPrediction of FGR1.Pregnant patients with abnormal first- or second-trimester maternal serum screening analytes may be at risk for fetal growth restriction and other placenta-mediated complications. Health care providers should use uterine artery Doppler assessment (where available) to identify those at the greatest risk of fetal growth restriction (strong, moderate).2.In the context of either clinical risk factors for fetal growth restriction or fetal anatomical ultrasound findings that suggest this condition, clinicians should obtain a baseline ultrasound assessment of fetal growth at 24–26 weeks. This may be combined with either uterine artery Doppler assessment and/or measurement of maternal circulating placental growth factor to inform a plan of fetal surveillance in the third trimester (strong, moderate).Prevention of FGR3.At the first antenatal visit, clinicians should discuss the following topics with patients in a supportive non-judgmental manner: smoking, alcohol consumption, recreational drug use, and maternal body-mass-index-specific gestational weight gain targets. This discussion may optimize a range of harm-reduction strategies (strong, high).4.Low-dose aspirin (150–162 mg/d) prophylaxis for the prevention of fetal growth restriction, started before 16 weeks gestation and continued to >34 weeks gestation, should only be used in patients considered at risk of developing preeclampsia (conditional, low).5.Clinicians should reserve the use of low-molecular-weight heparin in combination with low-dose aspirin for the prevention of fetal growth restriction associated with preeclampsia for the small group of patients at highest risk of developing severe placental pathologies (conditional, low).Detection of FGR6.Health care providers can use serial symphysis–fundal height measurements to detect fetal growth restriction in clinically low-risk patients with a body mass index <30 kg/m2 (conditional, moderate).7.Health care providers should use ultrasonography to detect fetal growth restriction in patients with a high body mass index (especially when >35 kg/m2), polyhydramnios, or large fibroids (instead of symphysis–fundal height measurements) (strong, moderate).8.Sonographers should calculate the estimated fetal weight using the Hadlock-3 formula (Log10 weight =1.326 – 0.00326∗abdominal circumference∗femur length + 0.0107∗head circumference + 0.0438∗abdominal circumference + 0.158∗femur length), applied to ultrasound measurements of head circumference, abdominal circumference, and femur length (strong, moderate).9.Health care providers should interpret fetal growth by plotting estimated fetal weight on an ultrasound-based fetal growth chart derived from uncomplicated pregnancies (strong, moderate).10.Routine third-trimester ultrasound examinations are not recommended over serial symphysis–fundal height measurements and selective use of ultrasound in low-risk pregnant individuals because this practice does not reduce the overall risk of either stillbirth or adverse perinatal outcomes (strong, moderate).Investigations in Pregnancies with Suspected Fetal Growth Restriction11.Suspected fetal growth restriction should be systematically assessed by the health care provider with a detailed history, maternal serum screening for relevant congenital infections, and detailed sonographic assessment to establish the diagnosis and underlying cause of the concerning findings and to differentiate a fetus that is healthy but small for gestational age from one with placenta-mediated fetal growth restriction or impaired growth potential caused by an underlying genetic disorder, malformation, or infection (strong, high).12.When fetal growth restriction is suspected from viability to 36 weeks, the measurement (where available) of either placental growth factor alone, or as a ratio of soluble fms-like tyrosine kinase-1 to PlGF (sFlt1/PlGF ratio test) may help clinicians identify growth-restricted fetuses affected by underlying placental disorders (conditional, moderate).13.When a trans-placental fetal infection is the suspected cause of early-onset fetal growth restriction, a maternal serum ToRCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex) screen should be initiated, with cytomegalovirus infection being the most commonly-identified disease. Patients with suspected congenital infections should be referred to the designated regional maternal–fetal medicine centre for further evaluation (strong, moderate).14.A non-invasive prenatal screening test for common aneuploidies may be provided to determine a genetic cause for fetal growth restriction, but given the range of genetic disorders associated with fetal growth restriction, normal results may be of limited value (strong, high).15.Genetic consultation and amniocentesis (for chromosomal microarray of fetal DNA and molecular analysis for congenital infections) should be offered to patients with suspected early-onset fetal growth restriction, especially in the presence of structural abnormalities, polyhydramnios, or multiple soft markers and when there is no evidence of a placental basis for fetal growth restriction (strong, high).16.Clinicians should be aware that the risk of developing preeclampsia is high in pregnant individuals with suspected early-onset fetal growth restriction and should therefore provide education and serial assessments, especially if circulating angiogenic protein levels are abnormal (i.e., low placental growth factor or an elevated soluble fms-like tyrosine kinase-1 to placental growth factor ratio) (strong, moderate).Management of Early-Onset Fetal Growth Restriction17.Clinicians should primarily use a combination of Doppler studies (uterine artery, umbilical artery, middle cerebral artery, cerebroplacental ratio, and ductus venosus Doppler) to identify and monitor early-onset (<32 weeks) fetal growth restriction (strong, high).18.Health care providers should not use non-stress testing, computerized cardiotocography (where available), or full or modified biophysical profiles in isolation to monitor early-onset fetal growth restriction but as an adjunct tests between ultrasound appointments and during in-patient care (conditional, moderate).19.When fetuses with early-onset growth restriction show early umbilical artery Doppler waveform abnormalities (elevated resistance, reflected by pulsatility index >95th percentile), they should be assessed weekly using middle cerebral artery and ductus venosus Doppler examinations. Out-patient assessments are appropriate so long as the umbilical artery changes remain stable and the ductus venosus Doppler findings are normal (strong, moderate).20.Clinicians should consider admission to hospital for daily surveillance when highly abnormal umbilical Doppler waveforms (i.e., reversed end-diastolic flow velocities) are observed, or when absent end-diastolic flow velocities in the umbilical artery are accompanied by abnormal middle cerebral artery or ductus venosus Doppler studies (strong, moderate).21.Clinicians should consider admission for daily in-patient monitoring when early-onset fetal growth restriction is complicated by either preeclampsia or other major comorbidities such as insulin-dependent diabetes (strong, moderate).22.Urgent delivery should be scheduled, irrespective of gestational age, when there is a maternal indication for delivery (e.g., severe preeclampsia complicated by uncontrolled blood pressures or HELLP [hemolysis, elevated liver enzymes, and low platelets] syndrome) (strong, high); when there is clinical evidence of placental abruption (strong, high); or in the presence of non-stress test tracing abnormalities (i.e., reduced variability or repetitive late decelerations) (strong, high).23.Clinicians may defer delivery until 30–32 weeks gestation in cases of reversed end-diastolic flow in the umbilical arteries and to 32–34 weeks in cases of absent end-diastolic flow, so long as ductus venosus Doppler and non-stress test findings are normal (strong, high).24.Clinicians should arrange a consultation with a neonatal pediatrician when prospective parents face the possibility of preterm delivery for early-onset fetal growth restriction (strong, moderate).25.Clinicians should administer a course of corticosteroids for fetal lung maturation prior to planned preterm delivery, followed by intravenous magnesium sulfate on the day of delivery for fetal neuroprotection. Both medications should follow the same protocols as for pregnancies not affected by fetal growth restriction (strong, moderate).26.Caesarean delivery is generally indicated for placenta-mediated early-onset fetal growth restriction and major Doppler abnormalities in either the umbilical arteries (absent or reversed end-diastolic flow velocities) or the ductus venosus (absent or reversed a waves) so as to avoid acute fetal compromise from attempted induction of labour (strong, moderate).27.Clinicians should provide extensive support to prospective parents making difficult decisions when the severity of early-onset fetal growth in the periviable period (23–26 weeks) presents an imminent risk of stillbirth or neonatal death (strong, moderate).Management of Late-Onset FGR28.Clinicians may use a variety of tools to monitor suspected late-onset fetal growth restriction. Standard of care methods comprise maternal monitoring of fetal movements, full or modified biophysical profile scoring, and non-stress testing. Umbilical artery Doppler assessment should not be used in isolation for monitoring (strong, moderate).29.Middle cerebral artery Doppler studies may be used as a monitoring tool but should ideally be combined with umbilical artery Doppler studies and interpreted by deriving the cerebro-placental Doppler ratio (middle cerebral artery pulsatility index / umbilical artery pulsatility index). Middle cerebral artery Doppler studies should be performed during fetal quiescence to avoid false-positive test results. An abnormal cerebro-placental ratio is interpreted as below the 5th percentile for gestational age and indicates, depending on gestational age, the need for either enhanced surveillance or delivery (conditional, low).30.Weekly assessments with full or modified biophysical profiles or non-stress tests are appropriate, especially when umbilical artery and middle cerebral Doppler findings are normal, the patient experiences normal fetal movements, and the estimated fetal weight and fetal abdominal circumference are between the 3rd and 9th percentiles (strong, low).31.Twice-weekly surveillance or delivery are indicated when the estimated fetal weight or abdominal circumference is below the 3rd percentile, or when additional observations suggest true fetal growth restriction. These findings include: abnormal uterine artery Doppler (mean pulsatility index >95th percentile); abnormal umbilical artery Doppler (pulsatility index >95th percentile); abnormal middle cerebral artery (MCA) Doppler (pulsatility index <5th percentile or cerebro-placental ratio <5th percentile); low amniotic fluid (maximum vertical cord-free pocket <2 cm); and highly abnormal appearance of the placenta, indicating multiple areas of tissue injury (strong, low).32.In cases of isolated mild small for gestational age (estimated fetal weight and abdominal circumference between the 3rd and 9th percentiles with normal Doppler studies and normal fluid), clinicians should consider delivery by 39 weeks gestation (strong, moderate).33.Clinicians managing uncomplicated late-onset fetal growth restriction (estimated fetal weight or abdominal circumference below the 3rd percentile with normal Doppler studies and normal fluid), should consider delivery by 37 weeks gestation (strong, moderate).34.Clinicians should recommend delivery by 37 weeks in late-onset fetal growth restriction when any of the following findings are present: abnormal umbilical artery Doppler (pulsatility index >95th percentile), abnormal cerebro-placental ratio (<5th percentile), abnormal full or modified biophysical profile, oligohydramnios, or concurrent diagnosis of preeclampsia (strong, moderate).35.In pregnancies with vertex presentation and no maternal indication for caesarean delivery, the decision to attempt vaginal delivery by induction of labour should take into account maternal age, parity, pelvic examination findings, ultrasound findings at admission, non-stress test findings, and parental wishes (conditional, low).36.Induction of labour for fetal growth restriction should only be performed in an in-patient setting with continuous fetal heart rate monitoring and not intermittent auscultation (strong, moderate).37.When performing induction of labour for suspected late-onset fetal growth restriction, a mechanical method of cervical ripening should be preferred over a prostaglandin agent where possible. Mechanical cervical ripening may be initially combined with low-dose oxytocin as an “oxytocin challenge test” of fetal health. Caesarean delivery should be performed if the fetal heart rate tracing becomes abnormal during the induction process or in early labour (strong, moderate).38.When fetal growth restriction is suspected at birth, the delivering clinician should send the placenta for pathological analysis, where available, especially if it exhibits grossly visible abnormalities (strong, moderate).Postpartum management and preconception counselling39.Following discharge from hospital, the growth-restricted infant should undergo serial neurodevelopmental assessments (strong, moderate).40.Patients who deliver a growth-restricted fetus are at short-term risk of impaired mental health, and thus deserve enhanced support during the postnatal period (strong, moderate).41.The maternal health benefits of effective contraception should be discussed in the early postpartum period, especially following caesarean delivery or admission of an infant to a neonatal intensive care unit. Delaying a subsequent pregnancy allows time for establishing the underlying diagnosis in small for gestational age infants and to inform care for future pregnancies (strong, moderate).42.Low dose aspirin (150–162 mg) may reduce the recurrence of fetal growth restriction associated with the development of preterm preeclampsia; the ability of aspirin to prevent recurrent fetal growth restriction in the absence of hypertension is less certain (conditional, low).43.In the absence of a maternal thromboembolic event, recurrent early pregnancy loss, or extensive placental infarction, maternal thrombophilia screening is not recommended following the delivery of a small for gestational age or growth-restricted infant (strong, moderate).44.All pregnancy care providers can provide initial management of subsequent pregnancies following the birth of a small for gestational age infant; however, early consultation with a regional maternal–fetal medicine unit is advised, especially for patients with complex comorbidities, maternal age >40 years, a severe adverse outcome in a previous pregnancy, or documentation of a major placental pathology diagnosis (strong, moderate).