Second Trimester Nuchal Fold – What Does It Mean?

CLINICAL ACTIONS:

The nuchal fold (NF) thickness is a measurement performed on prenatal ultrasound, and is the distance from the outer edge of the occipital bone to the outer edge of the skin in the midline. While both measurements are at the level of the fetal head or neck, a nuchal fold thickness, which is only performed in the second trimester, should not be confused with a first trimester nuchal translucency (NT) measurement.

If an enlarged second trimester nuchal fold measurement is obtained, next steps should include

  • Detailed anatomic study
  • If isolated finding
    • Offer NIPS screening (or Quad if NIPS unavailable or too expensive) or diagnostic testing (amniocentesis)
    • If NIPS is negative, no further aneuploidy evaluation is required

Note: ACOG guidance recommends offering prenatal screening for aneuploidy or invasive, diagnostic testing for all pregnant women regardless of age or aneuploidy risk

SYNOPSIS:

Second trimester thickened nuchal fold has a high specificity for aneuploidy.  ACOG and SMFM define an abnormal nuchal fold as 6mm in the 2nd trimester (typically performed between 15w0d and 22w6d). It is the most powerful second trimester sonographic marker for Trisomy 21.

KEY POINTS:

  • Can be differentiated from a cystic hygroma by the lack of fluid filled loculations
  • Trisomy 21 risk is increased by a factor of 17 when the nuchal fold is thickened
  • Can also be associated with single gene abnormalities

Learn More – Primary Sources:

ACOG Practice Bulletin 226: Screening for Fetal Chromosomal Abnormalities

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

Practical obstetrics info for your women's healthcare practice

Single Umbilical Artery, or the “Two Vessel Cord”: What Does it Mean? 

CLINICAL ACTIONS:

  • When single umbilical artery (SUA) is present, a detailed review of fetal anatomy including the heart and kidneys should be performed
  • While women have an option for invasive testing to determine with certainty the chromosomal status of the fetus, SUA in isolation does not appear to be associated with an increased risk of fetal aneuploidy

Note: ACOG guidance recommends offering prenatal screening for aneuploidy or invasive, diagnostic testing for all pregnant women regardless of age

SYNOPSIS:

A single umbilical artery (SUA), or two vessel cord, results from the absence of one of the arteries surrounding the fetal bladder. Typically, 2 arteries are present and contribute to the more common three vessel cord. The absence may involve either the right or left umbilical artery. SUA has a 0.6 to 1% prevalence during the fetal anatomy scan. It has been associated with fetal renal and cardiac anomalies, as well as low birth weight.

KEY POINTS:

  • May be associated with
    • Fetal cardiac and renal anomalies | Low birth weight | Adverse perinatal and newborn outcomes (see ‘Learn More – Primary Sources’ below)
  • Isolated SUA has a very good prognosis, although the patient should be reminded that there remains a 3 to 4% baseline risk of birth defects
  • SMFM recommends
    • No additional evaluation for aneuploidy (regardless if aneuploidy screening result is low risk or declined)
    • Recommended: Ultrasound in third trimester for growth
    • Consider weekly antenatal fetal surveillance beginning at 36w0d

Learn More – Primary Sources

Prenatally Diagnosed Single Umbilical Artery (SUA) – Retrospective Analysis of 1169 Fetuses

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

SMFM: Single umbilical artery: What you need to know

Isolated Single Umbilical Artery and Fetal Echocardiography: A 25-Year Experience at a Tertiary Care City Hospital

Isolated single umbilical artery is an independent risk factor for perinatal mortality and adverse outcomes in term neonates

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

Practical obstetrics info for your women's healthcare practice

Renal Pyelectasis on Prenatal Ultrasound – Next Steps?

Renal pyelectasis literally means “pelvis dilation” of the kidney, and is defined as an anteroposterior diameter of the renal pelvis of ≥ 4mm up to 20 weeks of gestation.

CLINICAL ACTIONS :

When 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, no further evaluation is required
    • Counsel patients that screening tests are not diagnostic and therefore there is still residual risk for chromosomal anomalies
  • If aneuploidy screen result is positive, refer for genetic counseling and consideration of diagnostic testing options
  • Ultrasound at 32 weeks of gestation is suggested to rule out persistent pyelectasis and possible obstruction of the urinary tract
    • If the renal pelvis is > 7 mm at 32 weeks, then post-natal follow up is suggested

If other anomalies are detected

  • ACOG guidance recommends offering invasive testing using microarray in the setting of fetal structural anomalies seen on prenatal ultrasound

SYNOPSIS:

Renal pyelectasis is reported in 0.6-4.5% of fetuses in the second trimester. It is most commonly a transient physiologic state in which the renal pelvis, the structure that is essentially the funnel for urine exiting the kidney into the ureter, is dilated and measures larger than what is considered normal for a particular gestational age. The presence of renal pyelectasis as an isolated finding, in the setting of a negative aneuploidy screen, is not itself an indication for invasive testing; however, ACOG does give all women the option (both high and low risk) for invasive testing.  Note, if the renal pelvis is still dilated in the third trimester, the urinary tract may require attention following delivery to ensure normal kidney function and prevent infection in the newborn.

KEY POINTS:

  • Normal renal pelvis measurement is up to 1cm throughout gestation
    • Values above 1cm are almost always pathological
  • Resolution of dilation based on second trimester measurement
    • Between 4 and 7 to 8 mm: 80% resolution
    • >9 mm: <15%
  • More commonly observed in male fetuses
  • A targeted ultrasound is essential to look for other fetal anatomic anomalies
  • Note: ACOG guidance recommends offering invasive, diagnostic testing for all pregnant women regardless of age and even in the presence of a normal anatomy scan
    • Offering invasive testing using microarray in the setting of fetal structural anomalies on prenatal ultrasound is recommended

Learn More – Primary Sources:

Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system)

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

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

Identification of copy number variations among fetuses with ultrasound soft markers using next-generation sequencing

Locate a genetic counselor or genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

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

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

Practical obstetrics info for your women's healthcare practice

Nuchal Translucency – First Trimester Measurement

WHAT IS IT?

Nuchal translucency (NT) is a fluid-filled space normally seen behind the fetal neck on ultrasound performed in the first trimester of pregnancy

  • A precise measurement of this space is used in first trimester aneuploidy screening in combination with levels of maternal serum markers [free or total hCG and pregnancy-associated plasma protein A (PAPP-A)] to provide an adjusted risk for fetal aneuploidy
  • Measurements should be performed between 11w0d and 13w6d weeks of pregnancy
    • ISPD suggests 12 weeks may be superior because
      • Patient scheduling may be easier and fetal anatomic visualization is better compared to 11 weeks
      • Screening performance is superior compared to 13 weeks
  • Determination of whether or not a measurement is normal requires an accurate measurement of fetal size using a crown rump length (CRL) measurement
  • Programs exist for credentialing purposes to provide education and ongoing mechanism for quality review and is a necessary requirement for optimal screening performance

KEY POINTS:

A fetal measurement >3.0 mm is an independent risk factor for fetal abnormalities and requires referral and further follow up

  • More commonly associated with aneuploidies such as Down syndrome and Turner syndrome, but may also be associated with other genetic syndromes, such as skeletal dysplasias
    • Larger NT may be associated with Noonan syndrome, especially in the context of other structural anomalies such as cardiac and renal findings
    • Approximately 10% risk with NT >3.0 mm and normal chromosomal complement
  • Fetal structural anomalies, including cardiac, abdominal wall and diaphragmatic defects, must be assessed by anatomical fetal ultrasound and fetal echocardiography
  • If the NT is sufficiently large to extend the length of the fetus with visible septations, this is called a ‘cystic hygroma’ and risk of aneuploidy is 50%
  • Other genetic syndromes and structural anomalies may be present even in those with normal karyotype
    • normal outcome may be <20%
  • Refer for high risk OB consultation and genetic counseling, and consider prenatal diagnostic testing
    • ACOG guidance recommends offering invasive testing using microarray in the setting of fetal structural anomalies seen on prenatal ultrasound

Learn More – Primary Sources:

ACOG Practice Bulletin 226: Screening for Fetal Chromosomal Abnormalities

Nuchal Translucency Quality Review

Fetal Medicine Foundation: Nuchal Translucency Scan

Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings

Position Statement from the Chromosome Abnormality Screening Committee on Behalf of the Board of the International Society for Prenatal Diagnosis

Testing for Noonan Syndrome after Increased Nuchal Translucency

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

Echogenic Intracardiac Focus – What is the Clinical Significance?

CLINICAL ACTIONS:  

An echogenic intracardiac focus (EIF) is a relatively common finding, even in otherwise normal fetuses. It is not a structural abnormality and considered a normal variant representing calcified deposits in the muscle of the fetal heart that appear as bright spots on prenatal ultrasound. SMFM considers an EIF a “soft marker” which is a “minor ultrasound finding” associated with an increased risk of aneuploidy.  

If EIFs Are Seen in Isolation  

  • Aneuploidy screening has not been performed 
    • Offer screening options  
      • NIPS or quad screen (if NIPS not available or too expensive) 
    • If aneuploidy screening is negative 
      • No further aneuploidy evaluation, follow up ultrasound or postnatal evaluation is recommended  
    • If aneuploidy screen result is positive 
      • Refer for genetic counseling and consideration of diagnostic testing options 

If Other Anomalies are Present  

  • Genetic counseling and offering diagnostic amniocentesis with microarray is indicated 

Note: SMFM guidance does not recommend diagnostic testing for isolated soft markers if aneuploidy screening is negative, but supports offering diagnostic testing as an option to all pregnant people regardless of aneuploidy risk 

SYNOPSIS

An EIF is the presence of a small (< 6mm) echogenic area in one or both of the cardiac ventricles, observed in at least two planes (ex. 4 chamber view, left ventricular outflow tract view) and as bright as bone. EIF may also be referred to as a papillary muscle microcalcification. EIFs are a fairly common second trimester finding, seen in 3 to 5% of euploid fetuses. Older studies described EIF as a soft marker for Trisomy 21, but subsequent literature has suggested a minimal risk with an isolated EIF.  

KEY POINTS:  

  • Low association with Trisomy 21 in the absence of other markers/anomalies 
  • Follow-up sonogram is not indicated for an isolated echogenic intracardiac focus with normal aneuploidy screening results 
  • EIFs are considered a normal variant and have no association with neonatal cardiac anomalies  

Learn More – Primary Sources:  

ACOG Practice Bulletin 226: Screening for Fetal Chromosomal Abnormalities 

ACOG Practice Bulletin 162: Prenatal Diagnostic Testing for Genetic Disorders 

ACOG Practice Bulletin 175: Ultrasound in Pregnancy 

ACOG Committee Opinion No. 682: Microarrays and Next-Generation Sequencing Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology 

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

  

Practical obstetrics info for your women's healthcare practice

Choroid Plexus Cysts – When is it Time to Worry?

CLINICAL ACTIONS:

The fetal choroid plexus produces CSF that leads to the normal expansion and development of the ventricular system. In some cases, fluid may get trapped, leading to the identification of choroid plexus cysts (CPCs) during prenatal ultrasound. The natural history of CPCs is resolution by 28 weeks. CPCs are not considered a structural brain abnormality, but are present in fetuses with trisomy 18 along with other multiple anomalies. An isolated CPC is a common finding in euploid fetuses.

Determining the Significance of CPCs

  • If CPCs are detected, a detailed anatomical study should be performed to identify other structural anomalies and findings associated with Trisomy 18 such as heart defects, abnormalities in the hands (“clenched fists”) and feet (“rocker-bottom”), growth restriction with polyhydramnios

If CPCs are seen in isolation with no other fetal abnormalities on ultrasound

  • If aneuploidy screening has not been performed
    • Offer screening options (NIPS or quad screen if NIPS not available or too expensive)
    • If screening result is negative, no further aneuploidy evaluation or follow up ultrasound is recommended
    • If aneuploidy screen result is positive, refer for genetic counseling and consideration of diagnostic testing options

If other anomalies or findings associated with Trisomy 18 are present on fetal ultrasound  

  • Genetic counseling and offering diagnostic testing with amniocentesis is indicated 

Note: SMFM guidance does not recommend diagnostic testing for isolated soft markers if aneuploidy screening is negative, but supports offering diagnostic testing as an option to all pregnant people regardless of aneuploidy risk

SYNOPSIS:

Choroid plexus cysts are present in 1 to 2% of all fetuses in the 2nd trimester and are due to CSF trapped in the choroid plexus(es). They may be single, multiple, unilateral or bilateral. CPCs are associated with trisomy 18, not Trisomy 21. CPCs generally resolve and if found in isolation are considered a normal variant.

KEY POINTS:

  • No increased risk of neurodevelopmental delay in genetically normal fetuses with CPCs
  • No need for prenatal or postnatal follow-up of isolated CPCs

Learn More – Primary Sources:

Fetal Imaging: Joint Executive Summary

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

ACOG Practice Bulletin 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