Twice the Joy, Twice the Questions
For expectant parents of twins, the pregnancy journey is filled with unique excitement and equally unique concerns. Down syndrome screening follows a different path when two hearts beat together in one womb. Twin pregnancies present special challenges for prenatal screening, from adjusted biochemical calculations to the complex interpretation of dual ultrasound scans. This article explores the fascinating science that helps parents and healthcare providers navigate this important aspect of twin pregnancy care, balancing accuracy with the comforting knowledge that most twin pregnancies result in healthy babies.
In singleton pregnancies, screening for Down syndrome (also known as trisomy 21) relies on established patterns: maternal age combines with specific biochemical markers in the mother's blood and ultrasound findings. However, twin pregnancies introduce additional variables that require sophisticated adjustments to these screening methods 2 .
Each twin contributes to the biochemical signals detected in maternal blood, meaning the presence of two placentas (dichorionic twins) or a shared placenta (monochorionic twins) significantly impacts how screening results are interpreted. In dichorionic twins, who each have their own placenta, the risk for Down syndrome is calculated separately for each fetus, then combined and adjusted to produce a "pseudo risk" for the entire pregnancy 2 .
The first-trimester combined test remains the cornerstone of Down syndrome screening in twins, just as in singleton pregnancies. This involves:
Measuring Pregnancy-Associated Plasma Protein-A (PAPP-A) and the free beta subunit of human chorionic gonadotropin (free β-hCG) 5
Measuring nuchal translucency (NT) - the fluid-filled space at the back of each fetus's neck
Research indicates that conducting both ultrasound and serum screening tests across the first and second trimesters provides the most effective approach for detecting Down syndrome 1 . For twin pregnancies, the gestational age must be calculated from the larger of the two crown-rump length measurements, according to NHS screening requirements 3 .
| Screening Component | Detection Rate in Dichorionic Twins | Detection Rate in Monochorionic Twins |
|---|---|---|
| First Trimester Combined Test | ||
| NT Measurement Alone | Varies based on individual fetus | More consistent between twins |
| Biochemical Markers | Requires specialized "pseudo risk" calculation | |
Given the increasing number of twin pregnancies resulting from assisted reproductive technology (ART), researchers have worked to validate whether standard screening adjustments remain accurate for this specific population. A controlled pilot study published in the Journal of Assisted Reproduction and Genetics addressed this important question 2 .
Researchers designed a nested controlled study comparing 19 sets of phenotypically normal dichorionic twins conceived via in vitro fertilization (IVF) with 80 spontaneously conceived singleton pregnancies, matched in a 1:4 ratio 2 . This careful matching helped ensure that any differences observed would likely stem from the twin pregnancy itself rather than other variables.
The study excluded pregnancies with complications that could affect results, such as:
All participants underwent the standard first-trimester combined screening test between 11-14 weeks of gestation, with measurements of nuchal translucency and the biochemical markers PAPP-A and free β-hCG 2 .
The study found no statistical differences in the maternal serum-free β-hCG and PAPP-A multiples of the median (MoM) values between the IVF twin pregnancies and singleton pregnancies 2 . This provided validation for the laboratory correction methods used to estimate Down syndrome risk in dichorionic twin pregnancies conceived after IVF.
Interestingly, researchers noted a 15% closer approximation to the laboratory median for PAPP-A and a 10% closer approximation for free β-hCG in twins compared to the singleton reference group 2 . This unexpected finding suggests that with proper adjustments, screening in twin pregnancies might achieve even better alignment with laboratory standards than singleton pregnancies in some cases.
| Parameter | Singleton Pregnancies (N=80) | Twin Pregnancies (N=19) | Statistical Significance |
|---|---|---|---|
| Maternal Age (years) | 32 (5.4) | 35 (4.4) | p=0.008 |
| Free β-hCG MoM | 1.20 (0.6) | 1.05 (0.5) | p=0.15 |
| PAPP-A MoM | 1.3 (0.8) | 1.2 (0.6) | p=0.21 |
| Gestational Age at Delivery (weeks) | 39.4 (1.0) | 34.6 (3.3) | p<0.001 |
Note: Risk assessment requires specialized calculation for twin pregnancies
Measures pregnancy-associated plasma protein A levels in maternal serum
Measures free beta subunit of human chorionic gonadotropin
Measures nuchal translucency thickness for each fetus
Integrates maternal age, biochemical markers, and NT measurements
Determines accurate gestational age
For parents expecting twins, the Down syndrome screening pathway involves:
Between 11-14 weeks to determine chorionicity (whether twins share a placenta) and measure nuchal translucency for each fetus
To measure PAPP-A and free β-hCG levels, with recognition that these markers may present differently in ART pregnancies 4
That incorporates maternal age, ultrasound findings, and adjusted biochemical markers using specialized software 3
Based on results, which may include non-invasive prenatal testing (NIPT) or discussions about diagnostic testing options 6
A "higher-chance" screening result does not mean definitively that either twin has Down syndrome. It indicates that further discussion with healthcare providers about additional testing options is warranted 6 . These options may include:
A more advanced blood test that analyzes fetal DNA in maternal circulation
Such as amniocentesis, which can provide definitive answers but carry slight procedure-related risks 7
Screening for Down syndrome in twin pregnancies represents a remarkable integration of advanced biochemistry, sophisticated ultrasound technology, and specialized risk calculation. While the process involves greater complexity than singleton screening, ongoing research continues to refine these methods to provide accurate information to expectant parents.
The validation of screening approaches for IVF-conceived twins demonstrates how prenatal care evolves to meet the needs of diverse populations 2 . As research continues, the scientific community's understanding of the subtle differences in marker expression between singleton and twin pregnancies will further enhance the accuracy and reliability of these important screening tools.
For parents navigating this journey, knowledge of the careful science behind twin pregnancy screening can provide reassurance that their unique situation is understood and accounted for in modern prenatal care. Through continued research and clinical refinement, the field moves ever closer to screening approaches that honor the uniqueness of every pregnancy—especially when there are two babies on the way.