Fetal Growth Restriction: Definition, Evaluation and Management

SUMMARY:

ACOG / SMFM released a guidance update on fetal growth restriction (FGR). While there is currently no clear consensus on the definition, evaluation, and management, FGR is associated with adverse perinatal outcomes. Therefore, timely diagnosis and management are key to optimizing long term benefit. Ultrasound and fundal height measurement are important physical exam diagnostic maneuvers. Early delivery and expectant management have similar outcomes thus creating deliberate birth plans should be discussed.

Key Terms and Definitions

  • FGR: EFW or AC <10th percentile for gestational age
    • Symmetric: Global growth restriction | Early insult
    • Asymmetric: Head-sparing with generally better outcomes
  • Small for gestational age (SGA): Newborn birthweight <10th percentile for gestational age

Risk Factors

Maternal Disease

  • Hypertensive disorders
    • Chronic hypertension
    • Gestational hypertension and preeclampsia
  • Kidney disease
  • Endocrine
    • Pregestational diabetes mellitus
  • Autoimmune
    • SLE
    • Antiphospholipid syndrome
  • Congenital heart disease (see ‘Learn More – Primary Sources’ for additional information)
    • Highest risk: Cyanotic heart disease | Reduced cardiac output

Note: Nutrition, oxygenation, and cardiovascular adaptation to pregnancy (placental perfusion) are underlying maternal factor mechanisms that impact fetal growth

Fetal Factors

  • Multiple gestation
  • Teratogenic exposures
    • Medications (e.g. fetal hydantoin syndrome)
    • Substance abuse (modifiable risk) including alcohol, cocaine and smoking
    • Intrauterine infections (e.g., CMV, rubella, syphilis)
  • Genetics:
    • Aneuploidy: Trisomy 13 and trisomy 18 commonly associated with FGR
    • Single gene disorders
    • Multifactorial: Congenital malformations (heart disease, gastroschisis)

Placental Anomalies

  • Abruption | Infarction | Circumvallate shape | Hemangioma | Chorioangioma
  • Umbilical cord anomalies
    • Velamentous or marginal insertion
    • Single umbilical artery

Note: Placental implantation abnormalities (e.g. placental accreta spectrum, previa) not associated with FGR

Evaluation and Screening Methods

  • Fundal height measurements
    • Begin at 24 weeks gestation
    • Perform at each prenatal visit
    • 3 cm discrepancy “proposed for identifying a fetus that may be growth restricted”
    • Limitations
      • Maternal obesity | Fibroids | Multiple gestation
  • Ultrasound
    • Preferred method of evaluation
    • Measurements include
      • BPD
      • HC
      • AC
      • FL
  • UA Doppler velocimetry
    • Reduces perinatal death when added to antepartum testing
    • Absent or reversed end-diastolic flow increases risk for perinatal mortality
    • Evaluation of the fetal ductus venosus has not been shown to improve perinatal outcomes (TRUFFLE study)

Note: No current evidenced based screening methods or preventative measures such as bed rest have demonstrated improved perinatal outcomes

KEY POINTS:

Management

  • Address modifiable risk factors, for example
    • Screen for fetal alcohol exposure
    • Discuss and encourage reduction in smoking and/or smoking cessation
      • Smoking is associated with 3.5 increased risk of SGA newborns
  • Genetic counseling
    • FGR alone may be associated with genetic syndromes and aneuploidy
    • Combined FGR and fetal structural abnormalizes increase aneuploidy risk and warrants genetic counseling referral
  • Depending on clinical scenario
    • Serial ultrasounds q3-4 weeks for growth and AFV
    • Do not measure fetal growth more often than every 2 weeks (measurements will be within error of the test)
    • Fetal assessment (NSTs or BPPs): “…should not begin before a gestational age when delivery would be considered for perinatal benefit”
  • Mode of delivery
    • Reserve cesarean section for obstetric/neonatal indications
    • Cesarean section and is not indicated for FGR in isolation

Timing of Delivery

  • Normal UA Doppler and EFW 3 to 10th percentile: 38w0d to 39w0d
  • EFW <3rd percentile (severe FGR): 37w0d
  • Decreased UA flow without absent end diastolic flow: 37w0d to 37w6d
  • Absent end diastolic flow: 33w0d to 34w0d
  • Reversed end diastolic flow: 30w0d to 32w0d
  • With oligohydramnios or concurrent conditions (e.g., preeclampsia, chronic hypertension): 34w0d to 37w6d

Note: If delivery planned <34 weeks, deliver at center with a NICU and consult MFM

When to Give Antepartum Corticosteroids

  • < 33w6d (anticipated delivery)
  • 34w0d-36w6d (late preterm) if risk
    • No previous corticosteroids
    • Anticipate delivery within 7 days

Note: “Consider” magnesium sulfate (neuroprotection) if delivery <32w0d

Future Pregnancies

  • Counsel regarding 20% recurrence risk
  • Review history to identify modifiable factors and/or treat maternal disease
  • In subsequent pregnancies

…it may be reasonable to perform serial ultrasonography for growth assessment, although the optimal surveillance regimen has not been determined.

Maternal history of a prior SGA newborn with normal fetal growth in the current pregnancy is not an indication for antenatal fetal heart rate testing, biophysical profile testing, or umbilical artery Doppler velocimetry

Note: There is insufficient evidence to routinely administer aspirin to prevent SGA in this population

Learn More – Primary Sources

ACOG Practice Bulletin 227: Fetal Growth Restriction

Effect of Maternal Heart Disease on Fetal Growth

Locate a Maternal Fetal Medicine Specialist

Maternal Fetal Medicine Specialist Locator-SMFM

Does Enoxaparin Prevent Preeclampsia?

PURPOSE:

This study by Groom et al. (AJOG, 2017) aimed to determine if enoxaparin, a low molecular weight heparin blood thinner, can be used to prevent preeclampsia and small-for-gestational-age pregnancy in women who have a prior history of these conditions.

METHODS:

Randomized Clinical Trial (RCT)

RESULTS:

149 women with a history of preeclampsia or small-for gestational-age pregnancy were enrolled in the study. 77 received standard high-risk care, and 72 received high-risk care as well as a subQ injection of 40mg (4000 IU) enoxaparin daily from time of enrollment to delivery or 36 weeks’ gestation (whichever came first). Enoxaparin did not reduce the risk of preeclampsia and small-for-gestational-age neonates in women with a history of these complications.

Learn More – Primary Sources:

Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a history: a randomized trial

Guidance on How to Manage the Suboptimally Dated Pregnancy

SUMMARY:

ACOG has reaffirmed a committee opinion defining ‘suboptimally dated’ pregnancies as those without an ultrasound before 22w0d to confirm or revise the EDC. (For guidelines on how to revise discrepant LMP and ultrasound, see the guideline summary in ‘Related ObG Topics’ below).

KEY POINTS:

  • Optimal time for dating remains the first trimester
  • No role for elective delivery in women with suboptimally dated pregnancies
  • Consider an ‘interval’ ultrasound scan for fetal weight and gestational age 3 to 4 weeks after the first scan
    • Fetal growth restriction may be identified
  • Consider antepartum fetal surveillance at 39-40 weeks
  • Amniocentesis for lung maturity is not part of routine management
  • Antenatal corticosteroid administration for anticipated preterm delivery:
    • 24 weeks – 34 weeks
    • 34 0/7 weeks – 36 6/7 weeks if delivery imminent within 7 days
    • Not recommended for presumed term delivery

The recommendation on timing of delivery states

Given concern that a full-term or late-term suboptimally dated pregnancy could actually be weeks further along than it is believed to be, late-term delivery is indicated at 41 weeks of gestation when gestational age is uncertain, using the best clinical estimate of gestational age.

Learn More – Primary Sources:

ACOG Committee Opinion #688: The management of suboptimally dated pregnancies

When to Introduce Aspirin to Reduce Risks of Preeclampsia?

PURPOSE:

This study by Roberge et al. (AJOG, 2017) surveyed previously performed randomized control trials (RCTs) to determine at what point during pregnancy aspirin should be introduced to reduce the risk of preeclampsia.

METHODS:

Systematic Review and Meta-Analysis

RESULTS:

This study analyzed 45 studies which included 20,909 women. Women received aspirin or a placebo starting at ≤ 16 weeks or > 16 weeks. Women who began taking aspirin ≤ 16 weeks displayed lower risk or preeclampsia and fetal growth restriction than those who began taking aspirin > 16 weeks. They also found that the greater the dose, the greater the decrease in risk.

Learn More – Primary Sources:

The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis

Diagnosing Preeclampsia – Key Definitions and ACOG Guidelines

WHAT IS IT?

Preeclampsia is a pregnancy specific hypertensive disease with multi-system involvement. It usually occurs after 20 weeks of gestation and can be superimposed on another hypertensive disorder. While preeclampsia was historically defined by the new onset of hypertension in combination with proteinuria, some women will present with hypertension and multisystemic signs in the absence of proteinuria. The presence of multisystemic signs is an indication of disease severity.

SUMMARY:

Diagnostic Criteria

Blood Pressure Criteria

  • Hypertension – systolic BP > 140 mm hg or diastolic BP > 90 mm hg or both
    • On two occasions at least 4 hours apart after 20 weeks gestations with previously normal BP
    • Considered ‘mild’ until diastolic BP > 110mm hg or systolic BP ≥160 mm Hg
  • Severe Hypertension – systolic BP > 160 mm hg or diastolic BP > 110 mm hg or both
    • Can confirm using a short time interval (e.g., minutes) to facilitate timely antihypertensive therapy

Note: Gestational Hypertension

  • ACOG defines gestational hypertension as “hypertension without proteinuria or severe features develops after 20 weeks of gestation and blood pressure levels return to normal in the postpartum period”
  • Caution and close follow-up is warranted as up to a half of women with gestational hypertension will go on to manifest signs an symptoms consistent with preeclampsia
  • Women with severe gestational hypertension, even in the absence of proteinuria should be managed similar to women with severe preeclampsia
  • ACOG states

Women with gestational hypertension with severe range blood pressures (a systolic blood pressure of 160 mm Hg or higher, or diastolic blood pressure of 110 mm Hg or higher) should be diagnosed with preeclampsia with severe features.

Proteinuria Criteria

  • 24 hour urine collection >300 mg protein or
  • Single voided urine protein/creatinine ratio ≥0.3
  • Dipstick reading of 2+ (use only if other quantitative methods not available)

Preeclampsia Definitions

Preeclampsia

  • Hypertension and proteinuria or
  • In absence of proteinuria, new-onset hypertension with the new onset of any of the following
    • Thrombocytopenia: Platelets <100 x 109/L
    • Renal insufficiency: serum creatinine >1.1 mg/dl or doubling of serum creatinine in the absence of other renal disease
    • Impaired liver function: Elevated blood concentrations of liver transaminases to twice normal concentration
    • Pulmonary edema
    • Neuro: Unexplained new-onset headache unresponsive to medication (without an alternative diagnosis) or visual symptoms

Preeclampsia with severe features

  • Preeclampsia diagnosis, above, with any of the following
    • Severe hypertension
      • On two occasions at least 4 hours apart while on bed rest (unless already on antihypertensive therapy)
    • Thrombocytopenia: Platelets <100 x 109/L
    • Impaired liver function (without an alternative diagnosis): Elevated liver transaminases greater than twice upper limit of normal or severe persistent right upper quadrant or epigastric pain not responsive to medications
    • Progressive renal insufficiency: serum creatinine >1.1 mg/dl or doubling of serum creatinine in the absence of other renal disease
    • Pulmonary edema
    • Neuro: Unexplained new-onset headache unresponsive to medication (without an alternative diagnosis) or visual symptoms

Note: The following are not diagnostic criteria for the diagnosis of preeclampsia or preeclampsia with severe features

  • Clinically evident edema
  • Rapid weight gain
  • Massive proteinuria
    • Does not qualify as a ‘severe feature’
  • Fetal growth restriction
    • ACOG states that while it is important to monitor fetal status, FGR in the setting of all other fetal assessment being within normal limits (e.g., AFV, Doppler), expectant management ‘may be reasonable’ if mother and fetus appear stable and no other clinical indication is present that would indicate the need for early delivery
  • Uric acid
    • Hyperuricemia in hypertensive pregnancy is not a diagnostic marker, but is an important finding as a risk factor for adverse maternal and fetal outcomes
      • Small for gestational age (SGA) infant
      • Prematurity
      • Risk for adverse maternal outcomes if include patients with preeclampsia and risks increase with increasing concentration of uric acid
    • May be warranted in the setting of ‘diagnostic dilemmas’ such as diagnosing superimposed preeclampsia in the setting of chronic hypertension

Learn More – Primary Sources

ACOG Practice Bulletin 222: Gestational Hypertension and Preeclampsia

National Partnership for Maternal Safety Consensus Bundle on Severe Hypertension During Pregnancy and the Postpartum Period

Plasma uric acid remains a marker of poor outcome in hypertensive pregnancy: a retrospective cohort study

Pre-eclampsia: pathophysiology and clinical implications

Aspirin Treatment for Women at Risk for Preeclampsia – ACOG, SMFM and USPSTF Recommendations

FINDINGS:

ACOG/SMFM have released guidance aligned with USPSTF regarding the use of low-dose aspirin during pregnancy to prevent preeclampsia.  When indicated, low-dose aspirin should be started between 12 to 28 weeks and continued until delivery.  Optimally, aspirin usage should begin <16 weeks.

Recommended (high risk)

  • Offer low-dose aspirin (81 mg/day) to women with 1 high risk factors
    • History of preeclampsia, especially if accompanied by an adverse outcome
    • Multifetal gestation
    • Chronic hypertension
    • Diabetes (Type 1 or Type 2)
    • Renal disease
    • Autoimmune disease (for example, systematic lupus erythematosus, antiphospholipid syndrome)

Moderate Risk Factors

  • Offer low-dose aspirin (81 mg/day) to women with ≥1 moderate risk factors
    • Nulliparity
    • Obesity (BMI >30)
    • Personal history
      • Low birthweight or SGA
      • Previous adverse pregnancy outcome
      • >10-year pregnancy interval
    • Family history of preeclampsia
      • Sister or mother
    • Social and demographic characteristics
      • Black race (as a proxy for underlying racism)
      • Lower income
      • Maternal age ≥35 years
    • IVF

Universal Implementation

  • Evidence supports a risk-based approach
  • ACOG/SMFM acknowledges that in some settings, a majority of patients will fall in to either high or moderate risk categories, and therefore

In these instances, universal implementation (eg, offering low-dose aspirin to all patients within such practices or institutions) may be medically reasonable

Not Recommended Without Preeclampsia Risk Factors

  • Low risk: Previous uncomplicated full-term delivery
  • Insufficient Evidence
    • Prior unexplained stillbirth (insufficient evidence)
    • Prevention of fetal growth restriction
    • Prevention of spontaneous PTB
  • No Benefit
    • Prevention of early pregnancy loss

USPSTF Guidance

  • The USPSTF recommends the use of low-dose aspirin (81 mg/d) as preventive medication for preeclampsia after 12 weeks of gestation in persons who are at high risk for preeclampsia as per categories above (B recommendation – offer or provide this service)

Benefits

  • The most recent systematic evidence review (see ‘Learn More – Primary Sources) provided more precise estimate of the association between aspirin and the prevention of perinatal mortality (4% to 44% reduction in fetal and neonatal deaths)
  • Otherwise, benefits of low-dose aspirin for women at risk for preeclampsia were similar to previous reviews with lower risks for the following (moderate certainty)
    • Preeclampsia: Pooled relative risk (RR) 0.85 (95% CI, 0.75-0.95)
    • Perinatal mortality: Pooled RR 0.79 (95% CI, 0.66-0.96)
    • Preterm birth: Pooled RR 0.80 (95% CI, 0.67-0.95)
    • Intrauterine growth restriction: Pooled RR 0.82 (95% CI, 0.68-0.99)

Harms

  • No significant association was found for
    • PPH or other bleeding-related harms
    • Rare perinatal or longer-term harms
  • Long-term child developmental outcomes in offspring from in utero exposure to low-dose aspirin
    • Follow-up data from the Collaborative Low-dose Aspirin Study in Pregnancy (CLASP), found no differences in physical or developmental outcomes at 12 to 18 months

KEY POINTS:

  • Risk factors used for ACOG/SMFM recommendations only include factors obtained from the medical record
    • Uterine artery Doppler ultrasonography and biochemical markers are not included
    • ACOG/SMFM acknowledge that other studies, in particular the ASPRE trial (see ‘Related ObG Topics’ below), have incorporated ultrasound and maternal serum markers as well as doses >81 mg, but state

Further, the screening algorithm used includes first-trimester serum markers, including placental growth factor and pregnancy-associated plasma protein-A, as well as uterine artery dopplers, which limits the generalizability to a U.S. population. Therefore, a higher dose or doubling of the available 81-mg dose cannot be recommended at this time.

Screening for Preeclampsia

  • Various studies have incorporated not only clinical risk factors but also biochemical markers and ultrasound to determine which women are at risk for early onset preeclampsia and may benefit from aspirin prevention (see ‘Related ObG Topics’)
  • ACOG/SMFM considers the supporting data for the use of such combined risk assessment algorithms to be limited and without more prospective clinical utility trials, states that

…biomarkers and ultrasonography cannot accurately predict preeclampsia and should remain investigational.

Learn More – Primary Sources:

ACOG Practice Advisory: Low-Dose Aspirin Use for the Prevention of Preeclampsia and Related Morbidity and Mortality

ACOG Practice Bulletin 222: Gestational Hypertension and Preeclampsia 

USPSTF: Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

ACOG/SMFM Committee Opinion 743: Low-Dose Aspirin Use During Pregnancy

Deepest Pocket or AFI When Performing Prenatal Ultrasound?  

FINDINGS: 

There are two sonographic techniques that are used to measure amniotic fluid for the purpose of fetal assessment: (1) the amniotic fluid index (AFI) or (2) the single deepest vertical pocket (SDP). Oligohydramnios was defined as AFI ≤ 5 cm or the absence of a pocket measuring at least 2 × 1 cm. In a population of term pregnancies and using a multicenter randomized controlled trial design, the authors found:

  • In the AFI group, there were increased cases of oligohydramnios (9.8%) compared to SDP (2.2%) as well as increased induction of labor for this particular indication (P < 0.01)
  • There were significantly more abnormal fetal heart rate (FHR) tracings in the AFI group (32.3%) compared to the SDP group (26.2%), which was more pronounced in women who were otherwise low risk (P=0.03)
  • Neither test was better at predicting adverse pregnancy outcome, including NICU admissions, and cesarean section rates
  • The use of AFI resulted in more interventions for diagnoses of oligohydramnios with no benefit, thereby making SDP the preferable approach for assessing amniotic fluid, especially in low risk women

SYNOPSIS:

Measuring amniotic fluid volume remains an important part of fetal assessment.  The SAFE trial (Ultrasound Obstet Gynecol, 2016), a multicentered randomized controlled trial (RCT), was designed to answer the question as to whether AFI or SDP technique is better in predicting pregnancy outcome. 1052 pregnant women at term with singleton pregnancies were included in this trial which included low risk as well as high risk indications, such as gestational diabetes (GDM), hypertensive disorder, fetal growth restriction, placental insufficiency or intrahepatic cholestasis of pregnancy.

KEY POINTS:

  • AFI was associated with more women being identified with oligohydramnios, but without any significant benefit in perinatal outcome 
  • The SDP appears to be the favorable approach when estimating amniotic fluid volume in both high and low risk patients

Learn More – Primary Sources:

Single deepest vertical pocket or amniotic fluid index as evaluation test for predicting adverse pregnancy outcome (SAFE trial): a multicenter, open-label, randomized controlled trial.

Practical obstetrics info for your women's healthcare practice

Second Trimester Echogenic Bowel: Important Ultrasound Finding with Varied Causes and Some Serious Implications

CLINICAL ACTIONS:

Fetal bowel can sometimes appear bright on prenatal ultrasound depending on the transducer used and machine settings. However, echogenic bowel in the fetus is not a significant finding unless the bowel appears as bright as bone (the brightness of the iliac wing can be used a reference).  If the ultrasound report does confirm echogenic fetal bowel, further management should include

  • Aneuploidy screening
    • No previous aneuploidy screening
      • NIPS or quad screening
    • Negative aneuploidy screening
      • No further aneuploidy evaluation
  • Further work-up
    • Offer cystic fibrosis screening if not yet performed in current or prior pregnancy
    • Evaluate for cytomegalovirus (CMV) infection with IgG and IgM titers
    • Follow-up fetal growth scan in the third trimester to evaluate for growth restriction
    • If aneuploidy screening is positive, offer confirmatory diagnostic testing, referral for high-risk OB consultation and genetic counseling

SYNOPSIS:

Fetal echogenic bowel is present in up to 1.8% of second trimester ultrasound exams. It can be due to congenital cytomegalovirus infection, cystic fibrosis, intra-amniotic bleeding, fetal growth restriction, aneuploidy or gastrointestinal obstruction. Therefore, further work-up is warranted.

KEY POINTS:

  • Echogenic bowel is associated with aneuploidy (3 to 5%), the most common is Down syndrome (Trisomy 21)
  • If all identifiable causes are ruled out, fetal growth should be evaluated, as there is an association with fetal growth restriction
  • When isolated, normal fetal outcomes are likely. Pediatrics should be informed of the prenatal findings and work-up

Learn More – Primary Sources:

ACOG Practice Bulletin No. 226: Screening for Fetal Chromosomal Abnormalities

ACOG Practice Bulletin No. 162: Prenatal Diagnostic Testing for Genetic Disorders

Outcome of infants presenting with echogenic bowel in the second trimester of pregnancy

Society for Maternal-Fetal Medicine Consult Series #57: Evaluation and management of isolated soft ultrasound markers for aneuploidy in the second trimester

Locate a genetic counselor, genetics services or high risk OB:

Genetic Services Locator-ACMG 

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Locate a Maternal Fetal Medicine Specialist: SMFM

Practical obstetrics info for your women's healthcare practice

Short Femur on the Second Trimester Ultrasound Report: What to Include in the Management Plan?

CLINICAL ACTIONS:

A short femur is defined as a measurement below the 2.5 percentile for gestational age. This finding is typically identified on second trimester prenatal ultrasound, as femur measurements are part of the algorithm for pregnancy dating. While often there are no other abnormalities, the following should be included in the care plan:

  • Second trimester anatomical study to evaluate for short limb dysplasia

When short femur seen in isolation, with no other fetal abnormalities

  • If aneuploidy screening has not yet been done, then screening or diagnostic testing should be offered
  • If patient opts for aneuploidy testing and result is negative
    • Counsel patients that screening tests are not diagnostic and therefore there is still residual risk for chromosomal anomalies
    • ACOG guidance recommends offering prenatal screening for aneuploidy as an option for all pregnant women
    • Repeat sonogram in the 3rd trimester for growth
  • If aneuploidy screen result is positive, refer for genetic counseling and consideration of diagnostic testing options

If other anomalies are detected

  • Refer for genetic counseling and MFM assessment
  • ACOG guidance recommends offering invasive testing using microarray in the setting of fetal structural anomalies seen on prenatal ultrasound

SYNOPSIS:

The femur length should be measured with the bone perpendicular to the ultrasound beam and with epiphyseal cartilages visible, but not included in the measurement. The presence of a short femur may be associated with aneuploidy, intrauterine growth restriction and short limb dysplasia.

KEY POINTS:

  • The likelihood ratio for Down syndrome is 1.2 to 2.2, which indicates a minimal to small increase in the likelihood that the fetus will actually have this chromosomal abnormality
  • Evaluation of all the long bones is suggested to rule out limb dysplasia
  • ACOG guidance recommends offering
    • All patients the option of prenatal invasive testing or prenatal screening
    • Invasive testing using microarray in the setting of fetal structural anomalies seen on prenatal ultrasound

Learn More – Primary Sources:

ACOG Practice Bulletin No. 226: Screening for Fetal Chromosomal Abnormalities

Society for Maternal-Fetal Medicine Consult Series #57: Evaluation and management of isolated soft ultrasound markers for aneuploidy in the second trimester

Locate a Genetic Counselor or Genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Locate a Maternal Fetal Medicine Specialist

Maternal Fetal Medicine Specialist Locator-SMFM

Practical obstetrics info for your women's healthcare practice

What are the Implications of a Short Fetal Humerus? 

CLINICAL ACTIONS:

A short humerus is defined as a measurement below the 2.5 percentile for gestational age and may be identified during a prenatal ultrasound assessment. Consider the following next steps and referrals:

  • Second trimester anatomical study to evaluate for short limb dysplasia
  • If isolated finding
    • If aneuploidy screening has not yet been done, then screening or diagnostic testing should be offered
    • If patient opts for aneuploidy testing and result is negative, no further evaluation is required
    • Counsel patients that screening tests are not diagnostic and therefore there is still residual risk for chromosomal anomalies
    • ACOG guidance recommends offering prenatal screening for aneuploidy as an option for all pregnant women
    • If aneuploidy screen result is positive, refer for genetic counseling and consideration of diagnostic testing options
  • If other anomalies are detected
    • Refer for genetic counseling
    • ACOG guidance recommends offering invasive testing using microarray in the setting of fetal structural anomalies seen on prenatal ultrasound

SYNOPSIS:

The humerus should be measured with the bone perpendicular to the ultrasound beam and with the epiphyseal cartilages visible, but not included in the measurement. A short humerus is defined as a measurement below the 2.5 percentile for gestational age. The presence of short humerus can be associated with aneuploidy, intrauterine growth restriction and short limb dysplasia.

KEY POINTS:

  • Short humerus observed in the second trimester has a sensitivity of 9% in the prediction of Trisomy 21
  • If fetal aneuploidy screening test is ‘screen negative’ or a negative prenatal diagnostic test using amniocentesis or chorionic villus sampling indicates normal fetal chromosome complement, a short humerus should not be considered a risk factor for aneuploidy
  • ACOG guidance recommends offering
    • All patients the option of prenatal invasive testing or prenatal screening
    • Invasive testing using microarray in the setting of fetal structural anomalies seen on prenatal ultrasound
  • Evaluation of all the long bones using prenatal ultrasound is suggested to rule out limb dysplasia and other potential genetic syndromes
  • Third trimester ultrasound for growth is recommended

Learn More – Primary Sources:

ACOG Practice Bulletin 226: Screening for Fetal Chromosomal Abnormalities

SOGC: Fetal Soft Markers in Obstetric Ultrasound

ACOG Practice Bulletin No. 162: Prenatal Diagnostic Testing for Genetic Disorders 

Society for Maternal-Fetal Medicine Consult Series #57: Evaluation and management of isolated soft ultrasound markers for aneuploidy in the second trimester

Locate a Genetic Counselor or Genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Locate a Maternal Fetal Medicine Specialist

Maternal Fetal Medicine Specialist Locator-SMFM

Trisomy 13 – An Overview of Prenatal Findings and Outcomes

WHAT IS IT?

  • Trisomy 13 (47,XY,+13 or 47,XX,+13) is also referred to as Patau syndrome
  • Most affected individuals do not survive fetal/newborn life
    • Approximately 50% of Trisomy 13 pregnancies end in loss between 12 weeks to term
    • More than 80% of newborns will not survive past the first month of life
    • Approximately 5-8% of infants may survive the first year, but with high acuity intensive care
  • May affect almost every organ system but the following findings are particularly common and may be identified on prenatal ultrasound
    • Significant, symmetrical growth restriction
    • Midline cleft lip and palate
    • Occular anomalies: hypotelorism is most commonly seen; cylcopia may be present in severe cases
    • Proboscis
    • Congenital heart defects (90%)
    • Renal anomalies
    • Postaxial polydactyly
    • Omphalocele
    • Abnormal hand and foot posturing
    • CNS structural defects
      • Holoprosencephaly
  • Complications for survivors are severe and include:
    • breathing and feeding difficulties
    • Heart failure
    • Seizures
    • Deafness and visual impairment
    • Severe intellectual disability and developmental delay

SYNOPSIS:

Trisomy 13 is a condition caused by the presence of an extra chromosome (#13) that is present at the time of conception. In approximately 75% of cases, it is the result of nondisjunction during meiosis (Trisomy 13), which is usually a random occurrence. In 20% of affected individuals, chromosomal imbalance is the cause, inherited from a parent who has a balanced karyotype (i.e. Robertsonian translocation). A small proportion of affected individuals are diagnosed with mosaic Trisomy 13.

KEY POINTS:

  • Overall, this condition is present in approximately 1/16,000 live births
  • Risk increases with maternal age
  • ACOG requires all women be offered prenatal screening (biochemical/ cfDNA) or invasive testing (amniocentesis / CVS)
    • Screening tests used to detect fetal Down syndrome may also include risk assessment for Trisomy 13
    • Offer confirmatory testing following a positive screening test for Trisomy 13 due to the potential for false positive results
      • Strongly consider a false positive screening test if the prenatal ultrasound is normal as most affected fetuses will have multiple anomalies
  • If there is a family history or previous Trisomy 13 pregnancy, refer for genetic counseling

Note: ACMG provides healthcare professionals with open access ‘ACT Sheets’ to guide next steps following a positive NIPS report for trisomy 13 (see ‘Learn More – Primary Sources’ below)

Learn More – Primary Sources:

ACOG Practice Bulletin No. 226: Screening for Fetal Chromosomal Abnormalities

ACMG: Noninvasive Prenatal Screening via Cell-Free DNA [Trisomy 13: Positive Cell Free DNA Screen]

NIH-GARD: Trisomy 13

US NLM: Genetics Home Reference Trisomy 13

Locate a Genetic Counselor or Genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Locate a Maternal Fetal Medicine Specialist

Maternal Fetal Medicine Specialist Locator-SMFM