Snapshot A 41-year-old G3P1 presents to clinic 11 weeks pregnant. She has a history of 1 miscarriage and 1 uncomplicated live birth with no complications 10 years ago. Her daughter is healthy. She has no medical conditions. Vital signs are within normal limits. She receives first-trimester screening and a cell-free DNA test. Introduction Overview asseses if fetus has a genetic condition Epidemiology Incidence 1/150 live births with chromosomal abnormalities Risk factors advanced maternal age history of prior fetal aneuploidy or abnormality Pathogenesis Most from nondisjunction Some due to somatic mosaicism or translocations Studies First-trimester screening indications between 10-14 weeks gestational age serum labs serum free β-hCG or total hCG ↑ trisomy 21 ↑ trisomy 18 ↓ trisomy 13 pregnancy-associated plasma protein A (PAPP-A) ↓ trisomy 21 ↓ trisomy 18 ↓ trisomy 13 imaging ultrasound nuchal translucency measurement ↑ trisomy 21 ↑ trisomy 18 invasive studies chorionic villous sampling (sampling of prenatal villi) indications abnormal first trimester screen 10-13 weeks gestational age confirm with ultrasound prior to testing complications transverse limb abnormality (< 10 weeks) rupture of membranes chorioamnionitis miscarriage Rh sensitization Second-trimester screening indications 15-22 weeks gestation (best time 16-18 weeks) serum labs quadruple screen hCG ↑ trisomy 21 ↓ trisomy 18 alpha fetoprotein (AFP) ↓ trisomy 21 ↓ trisomy 18 dimeric inhibin A ↑ trisomy 21 no change or ↓ trisomy 18 unconjugated estriol ↓ trisomy 21 ↓ trisomy 18 invasive studies amniocentesis (sampling of amniotic fluid) indications abnormal quadruple screen 16-20 weeks gestational age confirm with ultrasound prior to testing complications rupture of membranes chorioamnionitis Sequential integrated screening first trimester imaging ultrasound nuchal translucency serum labs PAPP-A second trimester serum labs quadruple screen higher detection rates than either first or second trimester screening alone Cell-free DNA indications to detect fetal Down syndrome 10 weeks to term pregnant patients at high risk for fetuses with Down syndrome highest detection rate for Down syndrome higher false-positive rate for low-risk patients