In a 36‑week pregnancy with fetal growth restriction (from the 50th to the 6th percentile) and polyhydramnios, should chromosomal microarray analysis (CMA) be offered despite a negative first‑trimester genetic test?

Chromosomal Microarray Analysis in Late-Onset FGR with Polyhydramnios

Yes, chromosomal microarray analysis (CMA) should be offered in this case despite negative first-trimester genetic testing, because the Society for Maternal-Fetal Medicine explicitly recommends CMA when fetal growth restriction is accompanied by polyhydramnios, regardless of gestational age or prior screening results. 1

Primary Recommendation

The 2020 SMFM guidelines provide a Grade 1B recommendation (strong recommendation, moderate-quality evidence) stating: "We recommend that women be offered fetal diagnostic testing, including chromosomal microarray analysis, when FGR is detected and a fetal malformation, polyhydramnios, or both are also present regardless of gestational age." 1

This recommendation applies to your clinical scenario for several critical reasons:

• The presence of polyhydramnios with FGR creates a distinct high-risk category that warrants diagnostic testing independent of prior screening results 1
• First-trimester screening (whether cell-free DNA or traditional serum screening) is not equivalent to diagnostic testing and does not rule out all chromosomal abnormalities detectable by CMA 1
• CMA can detect submicroscopic deletions and duplications that are not identified by standard karyotyping or first-trimester aneuploidy screening 1

Why Prior Negative Screening Does Not Eliminate the Need for CMA

Limitations of First-Trimester Screening

• Cell-free DNA screening primarily targets common aneuploidies (trisomies 21,18,13, and sex chromosome abnormalities) but does not screen for microdeletion/microduplication syndromes or all chromosomal conditions 1
• First-trimester screening is a screening test, not a diagnostic test, and false-negative results occur 1
• The combination of FGR with polyhydramnios represents new clinical information that emerged after first-trimester testing and changes the risk assessment 1

Incremental Yield of CMA in FGR with Additional Findings

Research demonstrates significant diagnostic yield when CMA is performed in FGR cases with additional ultrasound findings:

• In non-isolated polyhydramnios (polyhydramnios with other findings like FGR), CMA reveals clinically significant chromosomal aberrations in 6.7-8.1% of cases beyond what karyotyping detects 2
• CMA provides a 4-10% incremental yield over standard karyotype in early-onset FGR without structural malformations 1
• When FGR is accompanied by polyhydramnios, the rate of pathogenic copy number variants increases substantially 2, 3

Clinical Context: Late-Onset FGR (36 Weeks) with Polyhydramnios

Your specific case involves several concerning features:

• Significant growth deceleration (50th to 6th percentile) indicating pathological growth restriction rather than constitutional smallness 1
• Polyhydramnios accompanying FGR is an unusual combination that raises suspicion for genetic syndromes, particularly those affecting swallowing or neuromuscular function 1, 2
• Late presentation does not reduce the importance of genetic diagnosis, as this information impacts neonatal management, recurrence counseling, and family planning 1

Specific Genetic Findings Associated with FGR and Polyhydramnios

Research on polyhydramnios with CMA testing reveals:

• Microdeletion/microduplication syndromes are frequently identified, with chromosome 17 abnormalities being particularly common 2
• Six microdeletion/microduplication syndromes were observed in one study of polyhydramnios, four of which involved chromosome 17 2
• These submicroscopic abnormalities would not be detected by first-trimester aneuploidy screening 1, 2

Practical Implementation

Testing Approach

• Offer amniocentesis with CMA as the primary diagnostic test 1
• CMA should be performed rather than standard karyotype alone, as it provides superior detection of clinically relevant copy number variants 1
• Consider cytomegalovirus (CMV) PCR testing if amniocentesis is performed, as CMV can cause both FGR and polyhydramnios 1

Counseling Points

• Explain that first-trimester screening does not replace diagnostic testing when new high-risk features emerge 1
• Discuss that CMA can identify genetic conditions affecting long-term neurodevelopmental outcomes that would impact neonatal care planning 1
• Address that even at 36 weeks, genetic diagnosis provides valuable information for delivery planning, neonatal resuscitation preparation, and family counseling 1

Common Pitfalls to Avoid

• Do not assume negative first-trimester screening is sufficient when new ultrasound abnormalities develop later in pregnancy 1
• Do not rely solely on standard karyotyping—CMA is specifically recommended and provides significantly higher diagnostic yield 1
• Do not dismiss the importance of genetic testing in late third trimester—the information remains clinically actionable for immediate neonatal management and future pregnancies 1

Additional Surveillance Considerations

Beyond genetic testing, this pregnancy requires:

• Detailed anatomic ultrasound examination to identify any structural anomalies that may have been missed or developed since earlier scans 1
• Umbilical artery Doppler assessment to evaluate placental function and guide delivery timing 1
• Serial growth assessments and antenatal surveillance given the significant growth deceleration 1