Calculate first-trimester screening risk for Trisomy 21, 18, and 13 using NT measurement, maternal age, nasal bone, and biochemistry markers.
First-trimester combined screening for chromosomal abnormalities uses the nuchal translucency (NT) ultrasound measurement alongside maternal age and biochemical markers to calculate individualized risk estimates for trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). This screening window is between 11 weeks 0 days and 13 weeks 6 days gestation, when the fetal crown-rump length measures 45–84 mm.
The nuchal translucency is the sonolucent space between the skin and soft tissue overlying the cervical spine of the fetus. Increased NT thickness is associated with chromosomal abnormalities, cardiac defects, and other fetal anomalies. The Fetal Medicine Foundation (FMF) developed the standardized NT screening algorithm that combines maternal age-related a priori risk with the NT likelihood ratio using Bayesian methods to produce patient-specific posterior risk estimates.
This calculator performs Bayesian risk calculation using maternal age priors, NT MoM-based likelihood ratios, and optional nasal bone assessment. It provides separate risk estimates for trisomy 21, 18, and 13, along with NT percentile classification and clinical guidance on follow-up testing (cfDNA, CVS, amniocentesis).
NT screening remains the foundation of first-trimester prenatal assessment. Unlike cfDNA, the NT ultrasound simultaneously evaluates fetal anatomy, detects major structural anomalies, confirms gestational age, and assesses the risk of chromosomal conditions. This calculator helps patients and providers interpret NT results within the context of maternal age and additional markers.
Posterior risk = (Prior × LR) / (Prior × LR + (1 − Prior)). Prior = maternal age-specific background risk. LR = Gaussian likelihood ratio from NT MoM distributions for affected vs unaffected pregnancies. NT MoM = observed NT / expected median NT for gestational age. High-risk cutoff: 1 in 150.
Result: T21 risk: 1 in 380 (low risk), T18: 1 in 986, T13: 1 in 2,800
A 35-year-old at 12+3 weeks with NT 1.5 mm (MoM 1.0) has an age-based prior T21 risk of 1 in 249. The NT of 1.5 mm is at the median for this GA, providing a likelihood ratio near 1.0, yielding a posterior risk of approximately 1 in 380. This is below the 1 in 150 cutoff, classified as low risk. No invasive testing recommended based on NT alone.
The most widely used NT screening algorithm was developed by Professor Kypros Nicolaides and the Fetal Medicine Foundation in London. The FMF algorithm uses a Bayesian approach that starts with the patient's age-specific a priori risk and modifies it with likelihood ratios derived from the NT MoM value, free β-hCG MoM, and PAPP-A MoM. The likelihood ratios are calculated from the log-Gaussian distributions of these markers in affected and unaffected pregnancies, with multivariate corrections for correlations between markers. The FMF certifies individual operators and software platforms to ensure quality control.
Prenatal aneuploidy screening has evolved dramatically over four decades. Second-trimester maternal serum screening (triple/quad screen) was the standard from the 1990s through the 2000s, achieving ~70% detection of trisomy 21. First-trimester combined screening (introduced in the early 2000s) improved this to ~85-90%. Cell-free DNA screening (available since 2011) now achieves >99% detection, but at higher cost and without the structural information provided by the NT scan. Current guidelines from ACOG, SMFM, and ACMG recommend offering some form of screening to all pregnant patients, with the specific approach depending on patient preferences, cost, and availability.
One of the most important but underrecognized benefits of NT screening is early detection of congenital heart defects (CHD). Fetuses with NT ≥3.5 mm and normal chromosomes have approximately a 5-7% prevalence of major CHD, compared to <1% in the general population. This enables early fetal echocardiography, prepared delivery planning, and timely neonatal intervention for critical cardiac lesions. The 11-14 week scan also identifies other structural anomalies (anencephaly, body wall defects, megacystis) at a stage where termination options are less complex.
An NT measurement above the 95th percentile for gestational age (typically ≥3.5 mm) is associated with increased risk for trisomy 21, 18, and 13, Turner syndrome, triploidy, and other chromosomal abnormalities. However, increased NT is also associated with structural anomalies including congenital heart defects (the most common), diaphragmatic hernia, skeletal dysplasias, and genetic syndromes even when chromosomes are normal. Approximately 70% of fetuses with NT ≥3.5 mm will have normal chromosomes but still warrant detailed cardiac and anatomical evaluation.
First-trimester combined screening (NT + biochemistry + maternal age) detects approximately 85-90% of trisomy 21 cases at a 5% false-positive rate. Adding nasal bone assessment increases detection to ~93%. Cell-free DNA (cfDNA/NIPT) has a detection rate of 99%+ with a 0.1% false-positive rate but is a screening test, not diagnostic. The gold standard for definitive diagnosis remains CVS (chorionic villus sampling) at 11-14 weeks or amniocentesis at 15-20 weeks, both with ~99.9% accuracy but ~0.5-1% procedure-related miscarriage risk.
cfDNA (NIPT) has higher sensitivity and specificity for trisomy 21 specifically, but NT screening provides additional information. An increased NT can detect cardiac defects, other chromosomal abnormalities, and genetic syndromes that cfDNA does not assess. ACOG recommends offering screening to all pregnant patients regardless of age. Some practices now use cfDNA as first-line screening with NT reserved for structural assessment. The combination of both provides the most comprehensive first-trimester evaluation.
A high-risk result (typically >1 in 150) on first-trimester screening means the test is positive, NOT that the baby has an abnormality. Most high-risk results are false positives. Next steps include genetic counseling to discuss options: (1) cfDNA as a secondary screen (higher specificity), (2) CVS for definitive first-trimester diagnosis (11-14 weeks), or (3) amniocentesis for definitive second-trimester diagnosis (15-20 weeks). The choice involves weighing the ~0.5-1% procedure-related loss risk of invasive testing against the desire for definitive information.
NT measurement technique is critical for screening accuracy. The NT must be measured in the mid-sagittal plane of the fetus, with the fetus in a neutral position (not hyperextended or flexed). Calipers must be placed ON the inner edge of the nuchal fold lines, perpendicular to the long axis. The maximum measurement from three technically adequate images should be used. Inter-operator variability is the biggest source of error. FMF certification requires operators to maintain ongoing audit and quality control metrics to ensure measurement reliability.
When NT measures ≥3.5 mm but chromosomes are normal (confirmed by CVS or amniocentesis), the fetus still has increased risk for structural anomalies. A detailed fetal echocardiography should be performed at 18-22 weeks (congenital heart defects are the most common association). A detailed anatomy scan should evaluate for diaphragmatic hernia, renal anomalies, and skeletal defects. If the NT was ≥6.5 mm, the risk of genetic syndromes (Noonan, Smith-Lemli-Opitz, etc.) is significant even with normal karyotype, and microarray analysis should be considered.