What are the next steps for a pregnant patient with a history of echogenic bowel on fetal ultrasound who received a negative Non-Invasive Prenatal Test (NIPT) result?

Management of Echogenic Bowel with Negative NIPT

Despite a negative NIPT result, echogenic bowel on fetal ultrasound requires further investigation because NIPT only screens for select chromosomal abnormalities and does not eliminate risk for other genetic disorders, structural abnormalities, infections, or cystic fibrosis that can present with this ultrasound finding. 1

Understanding the Limitations of Negative NIPT

• A negative NIPT reduces but does not eliminate risk for chromosomal abnormalities, and critically, NIPT does not screen for structural fetal abnormalities, infections, or single-gene disorders. 1
• NIPT analyzes cell-free DNA of presumed placental origin, which may not always represent the actual fetal karyotype due to confined placental mosaicism. 1
• Post-test counseling for negative NIPT results must emphasize that the test only screens for select conditions and does not reduce risk for other genetic disorders or structural abnormalities. 1

Comprehensive Workup for Echogenic Bowel

Detailed Ultrasound Evaluation

• Perform a targeted anatomic survey searching specifically for additional soft markers, structural defects, and placental abnormalities (such as cystic hygromas, cardiac defects, growth restriction, or polyhydramnios/oligohydramnios). 2
• Assess the echogenicity grade and persistence of the finding, as increased echogenic resolution, multiple soft markers, associated deformities, poor growth, and persistent echogenic bowel in the third trimester significantly increase the risk of adverse outcomes. 2
• Document whether the echogenic bowel is isolated or associated with other abnormalities, as isolated findings have better prognosis. 2, 3

Infectious Disease Screening

• Offer amniocentesis for cytomegalovirus (CMV) PCR testing, as congenital CMV infection is a critical cause of echogenic bowel with ultrasonographic sensitivity less than 50% for detecting infected neonates. 2
• Obtain maternal serology for CMV, toxoplasmosis, and parvovirus B19 to assess for congenital infections. 2
• The poor ultrasound sensitivity for CMV makes invasive testing particularly important when echogenic bowel is identified. 2

Genetic Testing Beyond NIPT

• Consider diagnostic testing with amniocentesis for chromosomal microarray analysis (CMA) to detect microdeletions, microduplications, and other structural chromosomal abnormalities not screened by NIPT. 1
• While NIPT may be negative for common trisomies, echogenic bowel can be associated with Turner syndrome and other sex chromosome aneuploidies that have lower positive predictive values on NIPT (29.5% for monosomy X). 4, 2
• CMA is particularly valuable as it can identify pathogenic copy-number variants and susceptibility loci for neurodevelopmental disorders that NIPT cannot detect. 5

Cystic Fibrosis Evaluation

• Offer cystic fibrosis carrier screening to both parents, as echogenic bowel is associated with cystic fibrosis and meconium ileus. 2, 3
• If both parents are carriers, proceed with amniocentesis for fetal cystic fibrosis mutation analysis. 2

Assessment for Intra-amniotic Hemorrhage

• Review the patient's history for recent bleeding, trauma, or invasive procedures, as fetal ingestion of blood products from intra-amniotic hemorrhage can cause transient echogenic bowel that may be benign. 2
• Serial ultrasounds can help determine if the finding resolves, suggesting a benign etiology. 2

Surgical Considerations

• Bowel dilatation with or without echogenicity is often predictive of bowel obstruction requiring postnatal surgery (intestinal atresia, meconium ileus, duplication cysts). 3
• Arrange for delivery at a tertiary care center with pediatric surgical capabilities if bowel obstruction is suspected. 3
• Reassure parents that surgical outcomes for these conditions are generally very good when appropriately managed. 3

Common Pitfalls to Avoid

• Never rely solely on negative NIPT to provide reassurance when structural abnormalities like echogenic bowel are present, as NIPT is not designed to detect fetal structural abnormalities or many of the conditions associated with this finding. 1
• Do not dismiss isolated echogenic bowel as benign without completing the infectious and genetic workup, particularly CMV testing given its poor ultrasound sensitivity. 2
• Avoid using placental tissue for chromosomal analysis if diagnostic testing is pursued, as confined placental mosaicism can lead to discordant results; amniotic fluid is the preferred specimen. 6, 7
• Ensure thorough genetic counseling emphasizing that NIPT results reflect placental karyotype and may differ from fetal karyotype. 7, 8