How is the risk of Down syndrome evaluated in a new pregnancy for a woman with a history of a previous baby with Down syndrome?

Evaluation of Down Syndrome Risk in a New Pregnancy with History of Previous Affected Baby

For a woman with a history of a previous baby with Down syndrome, diagnostic testing with amniocentesis or chorionic villus sampling (CVS) should be offered directly, rather than starting with screening tests, due to the significantly increased recurrence risk.

Risk Assessment for Down Syndrome with Previous History

When a woman has had a previous baby with Down syndrome, her baseline risk is altered compared to the general population:

• Family history of Down syndrome increases the a priori risk, depending on the degree of relatedness and mode of inheritance 1
• Previous affected pregnancy can be incorporated into the Down syndrome risk estimate using published algorithms 1
• The risk may indicate a familial translocation, which significantly increases recurrence risk

Diagnostic Testing Options

First Trimester:

• Chorionic villus sampling (CVS) between 10 weeks 0 days and 13 weeks 6 days 1
• Provides definitive chromosome analysis
• Earlier results allow for more options and time for decision-making

Second Trimester:

• Amniocentesis beginning at 15 weeks gestation 1
• Gold standard for definitive diagnosis
• Lower procedure-related risk than CVS

Screening Options (If Diagnostic Testing Declined)

If a woman declines invasive diagnostic testing, comprehensive screening should be offered:

First Trimester Combined Screening (11-13 weeks):

• Nuchal translucency (NT) measurement
• Maternal serum PAPP-A and free β-hCG or total hCG
• Maternal age risk assessment 2
• Detection rate approximately 83% with 5% false-positive rate 2

Second Trimester Quadruple Screen (15-20 weeks):

• MSAFP, hCG, uE3, and INH-A
• Detects approximately 75% of Down syndrome cases in women younger than 35 years with 5% positive screening rate 1
• Over 80% detection in women 35 and older 1

Integrated or Sequential Screening:

• Combines first and second trimester markers
• Full Integrated Test has detection rate of 92% at 5% false-positive rate 2

Non-Invasive Prenatal Testing (NIPT)

• NIPT has emerged as a highly accurate screening method with detection rate and specificity approaching 100% 3
• Analyzes cell-free fetal DNA in maternal blood
• Significantly reduces need for invasive procedures 4
• Following NIPT implementation, proportion of women choosing invasive prenatal diagnosis after high-chance biochemical screening decreased from 75% to 43% 4

Important Considerations

• All prenatal testing must be voluntary
• Genetic counseling is especially important with a family history of Down syndrome 1
• Reports should include clear interpretation, patient-specific risk estimate, and risk cutoff used 1
• Risk calculations should account for maternal age, gestational age, serum marker levels, and other factors 2

Pitfalls to Avoid

• Failing to distinguish between screening and diagnostic tests
• Reclassifying screen-positive results to negative based on revised dating 1
• Not considering the possibility of a translocation form of Down syndrome, which has higher recurrence risk
• Overlooking the importance of genetic counseling when there is a family history of Down syndrome

Remember that while screening tests provide risk assessment, only amniocentesis or CVS can provide definitive diagnosis of Down syndrome 2.