6/2024
What are fetal ultrasound soft markers?
It is recommended that all pregnant individuals be offered prenatal genetic screening testing and a fetal anatomy ultrasound at 18-22 weeks of pregnancy. Prenatal genetic screening testing with a quad screen or cell-free DNA (ie NIPT or NIPS) is the first step in screening a pregnancy for chromosomal abnormalities/differences (ie aneuploidy--having missing or extra chromosomes) like Down Syndrome, Trisomies 18 and 13, and differences in sex chromosomes, like monosomy X (Turner Syndrome). The second step is a fetal anatomy ultrasound in the second trimester, ideally at 18-22 weeks of pregnancy, to assess for fetal abnormalities.
When we look at the fetal anatomy, we look at two types of abnormalities: major defects and minor markers (soft markers). Major defects include abnormalities of the fetal anatomy that are pathologic and can cause dysfunction after birth, ie a heart defect, cleft lip/palate, or gastroschisis. Soft markers are not considered pathologic and do not typically cause dysfunction of the fetus and neonate. They may even go away during the course of the pregnancy. However, when we see them at the 18-22 week period of pregnancy, they alter the risk of a pregnancy having an ie aneuploidy like Down Syndrome. As a result, a detailed fetal anatomy ultrasound and fetal echo will be done. The results of the prenatal genetic screening testing can be used to further assess the risk of a pregnancy being affected by aneuploidy if a fetal isolated soft marker is seen. "Isolated" means no other soft markers are seen.
While fetuses with Trisomies 18 and 13 are likely to have major abnormalities, only 27% of fetuses with Trisomy 21 have a recognizable major abnormality on the 2nd trimester anatomy ultrasound. Soft markers are more common among fetuses with Trisomy 21 (eg, echogenic intracardiac focus, thickened nuchal fold, renal pelvis dilation or echogenic bowel) and Trisomy 18 (choroid plexus cysts). However, soft markers for aneuploidy are most commonly identified in chromosomally normal fetuses. As a result, soft markers cannot be used alone to rule out the diagnosis of Trisomy 21. When a soft marker is seen on the fetal anatomy, the risk of aneuploidy is considered individually along with the results of the prenatal genetic screening testing.
Next steps if an isolated soft marker is found
• Assessment of risk factors for aneuploidy, including maternal age, results of other screening or diagnostic tests, and family history
• Aneuploidy/antenatal prenatal genetic screening testing (ie cell-free DNA, quad screen or nuchal translucency) should be offered if not already done
• If screening is available, the finding should be placed in context with those results
• If there is a isolated soft marker and the aneuploidy testing result is negative/low risk, then no further risk assessment an testing is needed
• If other soft markers or abnormalities are identified or the a prenatal genetic screening testing is positive/high risk, then genetic counseling, maternal–fetal medicine consultation, or both are recommended
Urinary tract dilation
Renal pyelectasis/pelviectasis is an increased collection of urine in part of the fetal kidney called the renal pelvis. When the renal pelvis measures >= 4mm before 20 weeks it is considered abnormal. Fetal renal pyelectasis is a common finding on 2nd trimester ultrasound, occurring in 0.5-4.5% of fetuses. In 80% (8 out of 10) of pregnancies, pyelectasis resolves during the pregnancy or after delivery without any treatment.
Additional ultrasounds may be done to determine if the amount of urine has decreased, remained the same, or increased. A repeat ultrasound around 32 weeks is recommended for all fetuses with pyelectasis, but more frequent monitoring may be recommended if the renal pelvis measurement is larger. Fetal renal pyelectasis is associated with Trisomy 21 and other renal pathology. If there is no prenatal genetic screening testing, counseling and a discussion on cell-free DNA testing or quad screen is recommended. If prenatal genetic screening testing is low risk/negative no further testing for aneuploidy is recommended.
Echogenic bowel
Fetal echogenic bowel means the fetal small bowel is as echogenic or bright as fetal bone on ultrasound. Isolated fetal echogenic bowel diagnosed on 2nd trimester ultrasound is a transient, idiopathic finding in approximately 0.5% of fetuses. It is associated with intra-amniotic bleeding, fetal cystic fibrosis (CF), fetal aneuploidy (e.g. trisomy 21, 13, 18), congenital infection {e cytomegalovirus (CMV), other viral infections, and toxoplasmosis}, primary gastrointestinal pathology (e.g. obstruction, atresia, perforation), intrauterine growth restriction and fetal demise. Viral, toxoplasmosis, and CF testing may be offered. Growth ultrasounds to monitor fetal growth may be recommended.
If no previous prenatal genetic screening testing, counseling and a discussion of options for cell free DNA testing or quad screen is needed. If prenatal genetic screening testing is negative/low risk, additional testing for aneuploidy is not indicated.
Echogenic intracardiac focus (EIF)
An EIF is a small, echogenic area within the fetal cardiac ventricle(s) of the heart that has a sonographic brightness equivalent to fetal bone. It is not a structural or functional cardiac abnormality. EIF is seen in 15-20% of fetuses with Trisomy 21 and 4-7% of chromosomally normal fetuses. Prevalence as high as 30% in fetuses of Asian parents. If prenatal genetic screening testing is normal/low risk, it is considered a normal variant and not clinically significant. If there is no prenatal genetic screening and an isolated EIF, counseling and a discussion of options for cell free DNA testing or quad screen is needed. No specific follow-up of isolated EIF is recommended.
Choroid plexus cyst (CPCs)
The choroid plexus is a sponge-like structure within the lateral ventricle on each side of the fetal brain that produces cerebrospinal fluid. A choroid plexus cyst is small fluid-filled structure within the choroid plexus. CPCs appear as echolucent cysts within the echogenic choroid. A CPC is not considered a structural or functional brain abnormality and is seen in 1-2% of chromosomally normal fetuses in 2nd trimester. If a major structural anomaly is present in addition to CPC, the probability of Trisomy 18 is 37%. If prenatal genetic screening testing is normal, it is considered a normal variant and not clinically significant. If no prenatal genetic screening testing is available, counseling and discussion of cell-free DNA testing or quad screen is recommended.
Thickened nuchal fold
ACOG defines an abnormal nuchal fold as ≥ 6mm in the 2nd trimester (typically performed between 15w0d and 22w6d of pregnancy). The presence of a thickened nuchal fold in the second trimester has a high specificity for aneuploidy. It is the most powerful second trimester ultrasound marker for Trisomy 21. It can also be associated with single gene abnormalities. A thickened nuchal fold is not the same as a cystic hygroma or first trimester nuchal translucency.
If there is no prenatal genetic screening testing, counseling and discussion on cell-free DNA testing or quad screen is recommended. If the prenatal genetic screening testing is negative/low risk serum, a discussion of options for no further aneuploidy evaluation or diagnostic testing via amniocentesis is recommended.
Absent or hypolastic nasal bone
Sometimes the nasal bone is absent or the nasal bone is small on midsagittal view of the fetal profile. This varies by race/ethnicity. Absent nasal bone occurs in 30-40% of fetuses with Trisomy 21 and 0.3-0.7 of chromosomally normal fetuses. Hypoplastic nasal bone occurs in 50-60-% of fetuses with Trisomy 21 and 6-7% of chromosomally normal fetuses. An absent nasal bone is also associated with craniofacial abnormalities and several genetic and chromosomal syndromes.
If not prior prenatal genetic screening testing, counseling and a discussion on cell-free DNA testing or quad screen is recommended. If prenatal genetic screening testing is low risk/negative, a discussion of options for no further aneuploidy evaluation or diagnostic testing via amniocentesis is recommended.
Single umbilical artery (SUA)
The umbilical cord contains 2 arteries and 1 vein. A SUA results when only one of the arteries is present. The incidence of SUA is 0.25% to 1% of all singleton pregnancies and up to 4.6% of twin gestations. A finding of an isolated SUA requires no additional evaluation for aneuploidy, regardless of whether previous aneuploidy screening results were low risk or screening was declined. SUA has been associated with an increased risk of fetal growth restriction and stillbirth, but data is conflicting. A third-trimester ultrasound to evaluate fetal growth and consideration of weekly antenatal fetal surveillance/testing beginning at 36 0/7 weeks of gestation for fetuses with an isolated SUA should be considered.
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