JA
EN
中文
Introduction
For many expectant mothers, knowing the fetus’s health status during pregnancy is extremely important. Among congenital chromosomal abnormalities, Down syndrome (Trisomy 21) is one of the most common. Early risk assessment before birth allows for appropriate medical care and family preparation. In this article, based on the latest research and guidelines, we explain in detail the types and characteristics of prenatal tests related to Down syndrome.
1. What Is Down Syndrome
Down syndrome is a genetic condition caused by having an extra copy of chromosome 21 (Trisomy 21). Its main features include intellectual disability, characteristic facial features, congenital heart defects, and gastrointestinal anomalies. Prenatal diagnosis enables planning for postnatal medical management, early intervention, and family support.
Incidence
Globally, the incidence of Down syndrome is approximately 1 in 700 to 1,000 live births (reference: Parker et al., 2010). The risk increases as maternal age rises, especially markedly after 35.
2. Classification of Prenatal Tests
Prenatal tests can broadly be classified into non‑invasive tests and invasive tests. Because their purposes, accuracy, and risks differ, the choice depends on the mother’s condition and preferences.
2‑1. Non‑Invasive Tests (Screening: NIPT etc.)
Non‑invasive tests assess the risk of chromosomal abnormalities (such as Down syndrome) by analyzing fetal DNA (cfDNA) in the mother’s blood.
(1) NIPT (Non‑Invasive Prenatal Testing)
- Characteristics: Assess fetal chromosomal risk by drawing maternal blood. Can be done from around 10 weeks’ gestation onward.
- Intended Use: Primarily for high‑risk pregnancies (advanced maternal age, ultrasound anomalies, history), but increasingly offered to low‑risk pregnancies as well.
- Accuracy: Sensitivity for Down syndrome exceeds 99 %, false positive rate about 0.1–0.5 % (Bianchi et al., 2014).
- Advantages: Non‑invasive for mother and fetus; virtually zero miscarriage risk.
- Disadvantages: A positive result is not definitive; invasive testing is required for confirmation.
(2) Serum Marker Tests (Maternal Serum Screening)
- Characteristics: Between 15 and 20 weeks gestation, measure specific proteins or hormone levels in maternal serum to estimate Down syndrome risk.
- Markers: AFP (alpha‑fetoprotein), hCG (human chorionic gonadotropin), uE3 (unconjugated estriol), Inhibin‑A, etc.
- Accuracy: Sensitivity approximately 70–80 %, false positive rate around 5 %. Precision is lower than NIPT but cost is lower and usage is more widespread.
- Advantages: Relatively simple risk evaluation during pregnancy.
- Disadvantages: If result is positive, invasive testing is needed for diagnosis.
2‑2. Invasive Tests (Definitive Diagnosis)
Invasive tests allow direct fetal chromosomal analysis and can definitively diagnose Down syndrome. However, they carry a small risk of miscarriage for mother and fetus.
(1) Amniocentesis
- Timing: From around 15 weeks onward
- Method: Under ultrasound guidance, amniotic fluid is drawn via the abdomen; fetal cells are cultured and analyzed.
- Accuracy: Almost 100 % definitive diagnosis.
- Risk: Miscarriage risk approximately 0.1–0.3 % (ACOG, 2016).
- Advantages: Can detect not only Down syndrome but also other chromosomal anomalies and genetic disorders.
- Disadvantages: Invasive, requiring careful decision-making.
(2) Chorionic Villus Sampling (CVS)
- Timing: Between 10 and 13 weeks
- Method: Sampling of placental (chorionic villus) tissue for chromosomal analysis.
- Accuracy: Provides definitive diagnosis.
- Risk: Miscarriage risk roughly 0.5 %, somewhat higher than amniocentesis.
- Advantages: Can obtain diagnosis earlier in pregnancy, allowing earlier decision-making.
- Disadvantages: It carries miscarriage risk and places burden on mother and fetus.
3. Key Points in Choosing a Test
When selecting a prenatal test, the following criteria should be considered:
- Type of test
- Accuracy
- Risk
- Timing
- Approximate cost
Here is a comparative summary:
| Test Type | Accuracy | Risk | Timing | Approximate Cost |
|---|---|---|---|---|
| NIPT | High (≈ 99 %) | Almost none | From 10 weeks onward | ~ ¥100,000 – 200,000 |
| Serum Marker Test | Moderate (70–80 %) | None | 15–20 weeks | Several thousand to ~ ¥10,000 |
| Amniocentesis | Nearly 100 % | Miscarriage risk 0.1–0.3 % | From 15 weeks onward | ~ ¥50,000 – 100,000 |
| CVS | Nearly 100 % | Miscarriage risk ~0.5 % | 10–13 weeks | ~ ¥50,000 – 100,000 |
(These figures serve as reference estimates; actual costs and risks differ by region and healthcare institution.)
4. Recent Trends in NIPT and Research Evidence
Recent research shows that NIPT is effective not only in high-risk pregnancies but also in general pregnancies:
- Bianchi et al., 2014, NEJM
In a study of 3,000 high-risk pregnancies, NIPT achieved a detection rate of 99.2 % for Down syndrome, with a false positive rate of 0.09 %, demonstrating strong accuracy. - Gil et al., 2015, Obstet Gynecol
In 1,200 low-risk pregnancies, NIPT outperformed standard serum screening and allowed non‑risk prenatal evaluation without miscarriage risk.
5. Ethical Considerations in Prenatal Testing
Even though prenatal tests have medical usefulness, they come with ethical implications:
- Acceptance of Results: When test results are positive, families must receive thorough genetic counseling and discussion.
- Freedom of Choice: Respect the pregnant woman’s autonomy in deciding whether to undertake testing or make prenatal decisions.
- Accuracy of Information: Understand that NIPT is a screening test; a positive result does not equal a definitive diagnosis.
6. Examples of Clinical Use
In practice, prenatal testing is often utilized through the following steps:
- Initial risk assessment at prenatal checkups (considering maternal age, ultrasound findings, history)
- Perform non‑invasive screening (NIPT or serum markers)
- If positive or high risk, proceed to invasive testing (amniocentesis or CVS) for definitive diagnosis
- With genetic counseling, formulate postnatal medical and support plans
This process enables expectant mothers and families to make informed decisions based on clear information.
7. Summary So Far
Prenatal tests for Down syndrome consist of non‑invasive screenings (NIPT, serum marker tests) and invasive tests (amniocentesis, CVS).
While NIPT offers high accuracy and safety and is increasingly used by general pregnancies, a positive result is not definitive and must be confirmed invasively.
Expectant mothers and families should choose the appropriate test under guidance from medical professionals, considering accuracy, risk, cost, ethics, and psychological aspects.
Proper use of prenatal testing makes it easier to plan for postnatal medical management and family support, enabling a safer and more reassuring pregnancy and childbirth experience.
8. National Recommendations & Guidelines for Prenatal Testing
Recommendations for prenatal testing vary by country and medical institution. Because NIPT is relatively new, its adoption and guidelines differ across regions.
- United States (ACOG)
Recommends NIPT for advanced‑age pregnancies (35+) or those with ultrasound anomalies; also permits offering it to low-risk pregnancies. - United Kingdom (NHS)
Performs serum marker screening for all pregnant women initially, and then offers NIPT to those at increased risk. NIPT is treated as a second-tier screening tool. - Japan (Japan Society of Obstetrics and Gynecology)
Uses early pregnancy screening (serum markers + NT measurement) for risk assessment; recommends NIPT for high-risk pregnancies. If NIPT is positive, confirm with amniocentesis or other methods.
These policies reflect each country’s balance among risk assessment, medical safety, and ethical considerations.
9. Cost & Access to Prenatal Testing
The cost of prenatal tests differs greatly depending on the method and the healthcare provider.
| Test Method | Estimated Cost | Insurance Coverage Possibility |
|---|---|---|
| NIPT | ~ ¥100,000 – 200,000 | Usually self‑pay (in Japan, often not covered by insurance) |
| Serum Marker Test | Several thousand to ~ ¥10,000 | Usually not covered by health insurance (some local subsidy may apply) |
| Amniocentesis | ~ ¥50,000 – 100,000 | If medically indicated, partial insurance coverage may be possible |
| CVS | ~ ¥50,000 – 100,000 | Mostly self-pay (insurance support possible if medically justified) |
Expectant mothers and families should include financial considerations in their decision-making. Although NIPT is expensive, its low risk and high accuracy give it considerable value.
10. Precautions Before Undergoing Prenatal Testing
Before undergoing prenatal testing, the mother and her family should understand the following:
Medical ethics & legal constraints
The purposes of testing and regulations concerning termination of pregnancy vary by country; thorough information gathering is essential.
Difference between screening and diagnosis
Despite high accuracy, NIPT is a screening test. A positive result necessitates invasive testing for confirmation.
Possibility of false negatives / false positives
Not all chromosomal abnormalities can be detected; rare misclassifications may occur.
Psychological impact
Results can impose emotional stress. Professional genetic counseling and psychological support are vital.
11. Summary & Practical Tips
- Risk evaluation for Down syndrome in pregnancy is divided into non‑invasive tests (NIPT, serum markers) and invasive tests (amniocentesis, CVS).
- NIPT offers high accuracy and safety, relieving psychological burden on expectant mothers, but it is not diagnostic.
- Amniocentesis and CVS can provide definitive diagnosis but carry a small risk of miscarriage.
- When choosing tests, one must weigh accuracy, risk, cost, ethics, and psychological factors together.
- Pre‑ and post-test counseling enables mothers and families to make well-informed decisions.
- With advances in prenatal testing technology, expectant mothers and families may increasingly have safer, more accurate testing options. Working collaboratively with medical professionals, choosing the appropriate tests, and obtaining support are crucial.
By properly using prenatal testing, expectant mothers and families can better plan medical care and support post-birth, making pregnancy and childbirth a more reassuring experience.
References
Parker SE, Mai CT, Canfield MA, et al. Updated National Birth Prevalence Estimates for Selected Birth Defects in the United States, 2004–2006. Birth Defects Res A Clin Mol Teratol. 2010;88(12):1008–1016.
Bianchi DW, Parker RL, Wentworth J, et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med. 2014;370:799–808.
Gil MM, Quezada MS, Revello R, Akolekar R, Nicolaides KH. Analysis of cell‑free DNA in maternal blood in screening for aneuploidies: updated meta‑analysis. Obstet Gynecol. 2015;126(3):514–524.
ACOG Practice Bulletin No. 163. Screening for Fetal Aneuploidy. Obstet Gynecol. 2016;127:e123–e137.
Bianchi DW, Chudova D, Sehnert AJ, et al. Noninvasive Prenatal Testing for Fetal Aneuploidy: Current Status and Future Prospects. Prenatal Diagnosis. 2015;35(6):621–626.
NHS Fetal Anomaly Screening Programme. Policy and Guidelines. 2023.
