Screening and Diagnosis

Carrier Screening

Preconception or early pregnancy

Parental DNA (Panels or targeted next-gen sequencing)

Autosomal recessive & X-linked disorders (CF, SMA, Fragile X, Hemoglobinopathies)

Autosomal recessive & X-linked disorders (CF, SMA, Fragile X, Hemoglobinopathies)

First Trimester Screen (FTS)

11.0 - 13.6 Weeks

PAPP-A, Free beta-hCG, and Ultrasound Nuchal Translucency (NT)

Trisomy 21 (Down), Trisomy 18 (Edwards), Trisomy 13 (Patau)

Screens for major aneuploidies; high NT can also indicate cardiac defects or genetic syndromes.

Quad Screen

15.0 - 22.6 Weeks

AFP, hCG, uE3 (unconjugated estriol), Inhibin-A

Trisomies 18, 21, and Open Neural Tube Defects (ONTDs)

T21: high hCG/Inhibin, low AFP/uE3. T18: all low. ONTD: high AFP. Less sensitive than NIPT.

MS-AFP Alone

15.0 - 20.0 Weeks

Maternal Serum Alpha-Fetoprotein

Open Neural Tube Defects (Spina Bifida, Anencephaly), Ventral Wall Defects

Elevated in ONTDs, Gastroschisis, Omphalocele. Low values can be associated with T21.

NIPT / cfDNA

From 10.0 Weeks to term

Cell-free fetal/placental DNA fragments in maternal circulation

Trisomies 13, 18, 21, Sex Chromosome Aneuploidies, Microdeletions (optional)

Highest sensitivity/specificity for T21 (>99%). Screening test only; false positives can occur (CPM).

Chorionic Villus Sampling (CVS)

Diagnostic (Invasive)

10.0 - 13.6 Weeks

Placental villi tissue sample (biopsy via transabdominal or transcervical approach)

Definitive fetal karyotype, microarray, or molecular single-gene diagnostic status

Allows 1st trimester diagnostic results. Small risk of miscarriage (~1/200 to 1/450). Cannot test for ONTDs.

Amniocentesis

Diagnostic (Invasive)

15.0 – 20+ Weeks (typically performed at 15–18 weeks)

Amniotic fluid sample obtained via transabdominal needle aspiration

Definitive fetal karyotype, chromosomal microarray, molecular single-gene testing, and open neural tube defect (ONTD) screening through amniotic fluid AFP

Provides highly accurate diagnostic results with a lower miscarriage risk than CVS (~1/500 to 1/1000). Performed later in pregnancy than CVS and results may take 1–2 weeks depending on the test ordered.

PUBS (Cordocentesis)

Diagnostic (Invasive)

From 20.0 Weeks to term

Fetal blood sampled directly from the umbilical vein under US guidance

Fetal hematocrit, rapid karyotyping, fetal infection status, severe blood dyscrasias

Technically challenging. Higher complication rate (~1-2%). Reserved for specific urgent clinical scenarios.

Anatomy Ultrasound

18.0 - 22.0 Weeks

Structural evaluation of fetal anatomy and structural markers

Major structural malformations, congenital defects, and soft markers of aneuploidy

Non-invasive. Direct visualization of fetal morphology. Guides timing and location of delivery.