Updates in Diagnosis and Management of Fetal Growth Restriction

Educational Objectives

The goal of this program is to improve management of fetal growth restriction (FGR). After hearing and assimilating this program, the clinician will be better able to:

1. Use professional guideline definitions to define degree of FGR.
2. Determine appropriate timing of delivery for a fetus with FGR.
3. Evaluate additional modalities available to manage FGR.

Summary

Background: fetal growth restriction (FGR) occurs in 3% to 10% of newborns; the diagnosis is an indication that the fetus may ultimately be small for gestational age (SGA); FGR is the second most common cause of neonatal morbidity and mortality (the first is preterm birth); the incidence of FGR in low- and middle-income countries is ≈6 times higher than high-income countries; the rate of FGR in the United States is higher among Black women and Indigenous populations

Neonatal outcomes: short-term outcomes — babies with FGR are at higher risk for hypoxic ischemic encephalopathy, hypothermia, hypoglycemia, hyperglycemia, polycythemia (caused by placental hypoperfusion), persistent pulmonary hypertension, bronchopulmonary dysplasia, necrotizing enterocolitis, other infections, retinopathy of prematurity, blindness, and fetal and neonatal death; long-term outcomes — FGR is associated with poor neurodevelopmental outcomes and an increased risk for chronic medical conditions (based on the Barker hypothesis)

Diagnosis: until 2020, the diagnosis of FGR was made using an estimated fetal weight (EFW) <10th percentile; the updated Society for Maternal-Fetal Medicine definition (2020) includes abdominal circumference (AC) percentile on ultrasonography (US); population-based standards must be used to determine percentiles; AC <10th percentile has ≈64% specificity for predicting FGR; EFW <10th percentile has ≈50% specificity; AC is slightly more sensitive than EFW; using both EFW and AC is ideal; reference standards — the Hadlock formula is widely used and based on information primarily from White women at a single United States institution; the National Institute of Child Health and Human Development standard collects population information from 12 states; INTERGROWTH standard evaluates 8 low-, middle-, and high-income countries; the World Health Organization standard includes data from 10 countries; the Hadlock standard is the most sensitive among those used within the United States

Classification: influences recommendations around timing of delivery; severe FGR is EFW <3rd percentile; early-onset FGR occurs <32 wk gestation, and late-onset FGR occurs ≥32 wk gestation; in symmetric FGR, all body measurements (eg, head circumference, humerus length, AC, femur length) are small; in asymmetric FGR, only the head circumference remains normal, suggesting blood shunting to the brain; while this may help determine the etiology of FGR, it does not change management

Etiology: maternal causes — include age, socioeconomic status, ethnicity, chronic disease, substance use, medications, hypertensive disorders of pregnancy, and maternal infection (malaria is one of the leading global causes of FGR); fetal causes — include a constitutionally small size, chromosomal abnormalities, genetic syndromes, congenital anomalies, infections, and multiple gestation; placental causes — include velamentous cord, single umbilical artery, placental infections, and placental masses that shunt blood away from the fetus

Initial steps following diagnosis: following diagnosis of FGR, verify the accuracy of pregnancy dating; evaluate the general maternal medical and obstetric history; measure maternal blood pressure; perform a detailed anatomic scan; counsel patients regarding diagnostic genetic testing and amniocentesis, and review any results; ≈10% of fetuses with FGR have copy-number variants which may be significant; consider testing for cytomegalovirus

Monitoring modalities: antenatal testing — includes nonstress testing (NST) and biophysical profiles (BPPs), both of which have equal sensitivity and specificity; growth US — should be performed every 2 to 4 wk; umbilical artery (UA) Doppler — measures placental resistance; even if a placental issue is absent, the final outcome of FGR always involves uteroplacental insufficiency (UPI); spiral artery remodeling is an underlying pathology for preeclampsia and UPI; UA Doppler measures blood flow velocity during systole and diastole; ideally, blood should flow from the fetus to the placenta during both phases; in UPI, end-diastolic flow (EDF) is absent or reversed; this is associated with a high risk for adverse perinatal outcomes (eg, mortality, intensive care use, cerebral hemorrhage, anemia, hypoglycemia, neurodevelopmental delay); prompt intervention (eg, hospital admission, betamethasone administration) and potential early delivery are indicated

Delivery considerations: depend on, eg, severe preeclampsia, placenta previa, fetal monitoring; a baby with EFW in the 3rd to 10th percentile with normal surveillance findings should be delivered at 38 to 39 wk gestation; babies with severe FGR (EFW <3rd percentile or abnormal UA Doppler findings) are delivered at 37 wk gestation; regardless of the presence of FGR, absent EDF warrants delivery at 33 to 34 wk gestation; reversed EDF warrants at 30 to 32 wk gestation; FGR alone is not an indication for cesarean delivery, as fetuses with FGR but normal UA Doppler can often tolerate labor; fetuses with absent or reversed EDF are at higher risk for complications during labor, and cesarean delivery is often recommended

Controversies in FGR

Screening using serum biomarkers: serum biomarkers are factors within maternal blood which can offer predictive value for particular obstetric outcomes; several biomarkers have been identified as markers of placental development and are elevated or decreased in various placenta-mediated conditions, including preeclampsia, placental abruption, stillbirth, and placenta accreta spectrum disorders; though individual biomarkers have poor to moderate predictive value for FGR, combining biomarkers improves sensitivity; prediction models — use serum biomarkers together with other characteristics to enhance prediction of FGR or SGA; one model includes maternal factors, EFW, uterine artery Doppler, placental growth factor, and alpha-fetoprotein; when acquired in the mid-second trimester, one prediction model using maternal factors, EFW, uterine artery Doppler, placental growth factor, and alpha-fetoprotein demonstrated a 100% detection rate of FGR <5th percentile among infants delivered before 32 wk gestation, but a detection rate of ≈38% among infants delivered at ≥37 wk gestation (Lesmes et al [2015]); another model using maternal factors and placental growth factor collected at 30 to 34 wk gestation demonstrated a detection rate of FGR of ≈85%; current recommendations — serum biomarkers are currently not recommended for use in clinical practice for prediction or management of FGR

Routine third-trimester growth US for low-risk pregnancies: Roma et al (2015) — demonstrated higher sensitivity for detection of FGR, but not worsened perinatal outcomes, with US at 36 wk vs 32 wk gestation; Bricker et al (2015) — demonstrated no significant difference with regard to rates of perinatal mortality, preterm birth, induction of labor, or cesarean delivery among women who received vs did not receive routine US for FGR; recommendations — no recommendation currently exists regarding universal third-trimester growth US

Additional Doppler studies: middle cerebral artery (MCA) Doppler — MCA Doppler is particularly useful for assessing for fetal anemia (with maternal alloimmunization), cardiovascular stress, and hypoxia; the pulsatility index evaluates the hemodynamics of blood within the MCA; evidence suggests that MCA Doppler has a low likelihood ratio for predicting neonatal mortality and adverse outcomes in FGR; MCA Doppler is not currently recommended to guide the management of FGR; ductus venosus (DV) Doppler — often used with absent or reversed EDF on UA Doppler; abnormal DV Doppler in the first trimester predicts high risk for aneuploidy; DV Doppler is used in the second and third trimesters to assess myocardial function and hemodynamics; in a triphasic wave, the a-wave represents contraction of the fetal atria; absent or reversed a-wave indicates advanced fetal compromise (20%-46% prediction rate of stillbirth ≤7 days); absent or reversed a-wave is found in ≈40% of fetuses with absent or reversed UA Doppler; affected fetuses usually have abnormal NST or BPP; DV Doppler is not currently recommended to guide the management of FGR

Readings

Borrell A, Martinez JM, Farre MT, et al. Reversed end-diastolic flow in first-trimester umbilical artery: an ominous new sign for fetal outcome. Am J Obstet Gynecol. 2001;185(1):204-207. doi:10.1067/mob.2001.114872; Bricker L, Medley N, Pratt JJ. Routine ultrasound in late pregnancy (after 24 weeks' gestation). Cochrane Database Syst Rev. 2015;2015(6):CD001451. doi:10.1002/14651858.CD001451.pub4; Fernandes M, Villar J, Stein A, et al. INTERGROWTH-21st Project international INTER-NDA standards for child development at 2 years of age: an international prospective population-based study. BMJ Open. 2020;10(6):e035258. doi:10.1136/bmjopen-2019-035258; Lausman A, Kingdom J. How and when to recommend delivery of a growth-restricted fetus: a review. Best Pract Res Clin Obstet Gynaecol. 2021;77:119-128. doi:10.1016/j.bpobgyn.2021.09.006; Lesmes C, Gallo DM, Gonzalez R, et al. Prediction of small-for-gestational-age neonates: screening by maternal serum biochemical markers at 19-24 weeks. Ultrasound Obstet Gynecol. 2015;46(3):341-9. doi:10.1002/uog.14899; Roma E, Arnau A, Berdala R, et al. Ultrasound screening for fetal growth restriction at 36 vs 32 weeks' gestation: a randomized trial (ROUTE). Ultrasound Obstet Gynecol. 2015;46(4):391-397. doi:10.1002/uog.14915; Society for Maternal-Fetal Medicine (SMFM). Electronic address: [email protected]; Martins JG, Biggio JR, Abuhamad A. Society for Maternal-Fetal Medicine consult series #52: diagnosis and management of fetal growth restriction: (replaces clinical guideline number 3, April 2012). Am J Obstet Gynecol. 2020;223(4):B2-B17. doi:10.1016/j.ajog.2020.05.010; Tsikouras P, Antsaklis P, Nikolettos K, et al. Diagnosis, prevention, and management of fetal growth restriction (FGR). J Pers Med. 2024;14(7):698. doi:10.3390/jpm14070698.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Mallampatti was recorded at Obstetrics and Gynecology Update: What Does the Evidence Tell Us?, held September 25-27, 2024, in San Francisco, CA, and presented by the University of California, San Francisco, School of Medicine. For infor­mation on upcoming CME activities from this presenter, please visit https://meded.ucsf.edu.continuing-education. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

OB720201

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.