​

​

​

First-Trimester Combined Screening Test in Pregnancy​

Abstract​

The first-trimester combined screening test is a widely accepted prenatal screening method for the assessment of fetal chromosomal abnormalities, particularly trisomy 21, trisomy 18, and trisomy 13. Conducted between 11 and 13+6 weeks of gestation, the test combines maternal serum biochemical markers with ultrasound parameters and maternal demographic factors. Although not diagnostic, it plays a critical role in early risk stratification and guides further prenatal management. This review summarizes the methodology, clinical significance, interpretation, and limitations of the first-trimester combined screening test.

Introduction​

Prenatal screening has become an integral component of obstetric care, aiming to identify pregnancies at increased risk for chromosomal abnormalities. Early screening allows couples to receive timely counseling and consider further diagnostic options. The first-trimester combined screening test has largely replaced second-trimester biochemical screening due to its higher detection rate and earlier timing in pregnancy.

Components of the First-Trimester Combined Screening Test​

Maternal Serum Biochemical Markers​

The biochemical component includes the measurement of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (free β-hCG). Reduced maternal serum PAPP-A levels and elevated free β-hCG levels are strongly associated with trisomy 21. These biomarkers reflect placental function and are influenced by gestational age.

Ultrasound Parameters​

Nuchal translucency (NT) thickness is the primary ultrasound marker used in first-trimester screening. Increased NT measurement is associated with chromosomal abnormalities, congenital heart defects, and genetic syndromes. Additional sonographic markers such as nasal bone absence, abnormal ductus venosus flow, and tricuspid regurgitation may further improve detection rates when assessed by trained operators.

Maternal Characteristics​

Maternal age, weight, ethnicity, smoking status, and gestational age are incorporated into computerized algorithms to calculate an individualized risk estimate.

Timing and Risk Calculation​

The test is optimally performed between 11 weeks 0 days and 13 weeks 6 days of gestation, corresponding to a crown–rump length of 45–84 mm. Results are expressed as a risk ratio. A commonly used cutoff value for high risk is 1:250, though this may vary according to national screening policies.

Clinical Performance​

The first-trimester combined screening test detects approximately 85–90% of fetuses with Down syndrome, with a false-positive rate of around 5%. The use of this screening strategy significantly reduces the number of unnecessary invasive diagnostic procedures.

Limitations​

Despite its effectiveness, the test has limitations. It does not provide a definitive diagnosis and is highly dependent on accurate ultrasound measurement and appropriate laboratory calibration. False-negative and false-positive results remain possible, necessitating proper counseling.

Conclusion​

The first-trimester combined screening test remains a cornerstone of prenatal screening. When performed correctly and interpreted within a comprehensive clinical framework, it provides valuable early risk assessment for chromosomal abnormalities and supports informed decision-making in prenatal care.

References (Vancouver Style)​

1. Nicolaides KH. First-trimester screening for chromosomal abnormalities. Semin Perinatol. 2005;29(4):190–194.
2. Kagan KO, Wright D, Spencer K, Molina FS, Nicolaides KH. First-trimester screening for trisomy 21 by free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A: impact of maternal and pregnancy characteristics. Ultrasound Obstet Gynecol. 2008;31(5):493–502.
3. Snijders RJ, Noble P, Sebire N, Souka A, Nicolaides KH. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal translucency thickness at 10–14 weeks of gestation. Lancet. 1998;352(9125):343–346.
4. Malone FD, Canick JA, Ball RH, et al. First-trimester or second-trimester screening, or both, for Down’s syndrome. N Engl J Med. 2005;353(19):2001–2011.
5. Wright D, Syngelaki A, Bradbury I, Akolekar R, Nicolaides KH. First-trimester screening for trisomies 21, 18 and 13 by ultrasound and biochemical testing. Fetal Diagn Ther. 2014;35(2):118–126.
6. American College of Obstetricians and Gynecologists (ACOG). Screening for fetal chromosomal abnormalities. ACOG Practice Bulletin No. 226. Obstet Gynecol. 2020;136:e48–e69.
7. Salomon LJ, Alfirevic Z, Audibert F, et al. ISUOG practice guidelines: performance of first-trimester fetal ultrasound scan. Ultrasound Obstet Gynecol. 2013;41(1):102–113.