What is the recommended approach for first trimester Down syndrome screening in twin pregnancies?

First Trimester Down Syndrome Screening in Twin Pregnancies

First trimester screening using nuchal translucency (NT) measurements combined with maternal age should be offered to women with twin pregnancies, as this approach is more effective than biochemical screening alone in multiple gestations. 1

Key Principle: Twins Require Modified Screening Approach

Down syndrome screening in twin pregnancies is fundamentally less effective than for singleton pregnancies due to pregnancy-specific versus fetus-specific marker characteristics. 1

Critical Distinction in Twin Screening:

• Serum markers (PAPP-A, free β-hCG, hCG) are pregnancy-specific - meaning the laboratory receives one combined value for both fetuses, making individual fetal risk assessment problematic 1
• NT measurements are fetus-specific - each twin can be measured individually, allowing separate risk assessment for each fetus 1

Recommended Screening Strategy

Primary Approach: NT-Based Screening

First trimester screening can be used in multifetal pregnancies, though women must be informed of the limitations. 1

The optimal strategy combines:

• Individual NT measurements for each twin (performed between 11-13 completed weeks' gestation) 1
• Maternal age 1
• Biochemical markers (PAPP-A and free β-hCG or hCG) if algorithms are available 1

Timing Specifications:

• NT measurements must be performed between 11 and 13 completed weeks' gestation 1
• Blood sampling for biochemistry typically occurs during the same gestational window, though some protocols collect samples several weeks before NT measurement 1
• Before 11 completed weeks, free β-hCG is useful but intact hCG is not 1

Performance Expectations and Counseling Points

Detection Rates in Twins:

• NT measurement alone detects approximately 70% of Down syndrome cases at a 5% false-positive rate in singleton pregnancies 1
• In twin pregnancies, detection rates are approximately 75-85% at a 5% false-positive rate when combining NT with biochemical markers 2
• This represents at least a 15% reduction in detection compared to singleton pregnancies when biochemical screening is included 2

Important Limitation:

Twin pregnancies, particularly those conceived via assisted reproduction, have higher false-positive rates primarily because standard algorithms incorporate maternal age, and biochemical marker interpretation is complicated by pregnancy-specific rather than fetus-specific values. 3

Technical Implementation

Algorithm Selection:

Published algorithms exist for assigning pregnancy-specific risk when combining NT and biochemistry in twins. 1 These algorithms can:

• Account for twin zygosity by observing chorionicity 1
• Provide individual risk assessments for each fetus based on their specific NT measurements 1

Whether and how a program interprets samples from twin pregnancies is left to the laboratory director's discretion. 1

Critical Counseling Requirements

Pre-Test Discussion Must Include:

• Screening effectiveness is reduced compared to singletons 1, 3
• Higher false-positive rates are expected, especially in assisted reproduction pregnancies 3
• NT measurement provides fetus-specific information, while serum markers do not 1
• All diagnostic options should abnormal results occur, including continuation, termination of entire pregnancy, or selective termination 2

Follow-Up for Abnormal Results:

• NT measurement ≥3.5 mm, even with low-risk screening result or normal karyotype, requires detailed anatomic ultrasound and/or echocardiogram 1
• Women should understand that invasive diagnostic testing (CVS or amniocentesis) carries procedure-related risks and provides definitive diagnosis 1

Common Pitfalls to Avoid

1. Do not rely solely on biochemical screening in twins - mid-trimester maternal serum screening has limited clinical value due to altered feto-placental endocrinology, particularly in assisted conception 3

2. Do not use singleton-derived risk cutoffs without modification - algorithms must account for twin-specific parameters 1

3. Do not fail to measure each twin individually - NT must be assessed separately for each fetus to provide meaningful risk stratification 1

4. Do not use predetermined age-based cutoffs alone - women should receive numerical risk estimates rather than just screen-positive/negative interpretations 1

Alternative: Invasive Testing

All women should have the option of invasive diagnostic testing (CVS if available, or amniocentesis) regardless of screening results. 1 This provides diagnosis of all major aneuploidies and large chromosomal rearrangements, bypassing the limitations of screening in twin pregnancies. 1