gynecology and obstetrics
Noninvasive Prenatal Fetal Screening Tests
Second Trimester Screening
Second-trimester screening may include Cell-free fetal nucleic acid testing or the multiple serum marker screening approach. Serum marker screening includes Maternal levels of beta-hCG, unconjugated estriol, alpha-fetoprotein, and sometimes inhibin A may be measured. This test may be used as an alternative or adjunct to First-Trimester Screening for chromosomal abnormalities. Maternal levels of serum alpha-fetoprotein (MSAFP) may be measured as a single serum marker to screen for Maternal serum screening for neural tube defects only (this approach doe not screen for Second-trimester multiple marker screening is used to help assess the risk of Down Syndrome (Trisomy 21) , Second-trimester screening may also include Prenatal Ultrasonography . Measurement of serum markers, adjusted for gestational age, are used mainly to refine estimates of Down Syndrome (Trisomy 21) risk beyond that associated with maternal age. With triple screening (ie, alpha-fetoprotein, hCG, and unconjugated estriol), sensitivity for Down syndrome is about 67 to 73%, with a false-positive rate of about 6% ( If maternal serum screening suggests Down syndrome, ultrasonography is done to confirm gestational age, and risk is recalculated if the gestational age is corrected. If the original sample was drawn too early based on the previously presumed gestational age, another one must be drawn at the appropriate time. Analysis of cfDNA does not depend on gestational age and thus is not prone to dating errors. In addition, amniocentesis is offered if serum screening indicates that risk of trisomy 21 exceeds a specific prespecified threshold (usually 1 in 270, which is about the same as risk when maternal age is>35). Quad screening can also assess risk of Trisomy 18 , indicated by low levels of all 4 serum markers. Sensitivity for trisomy 18 is approximately 100%; the false-positive rate is about 9% ( An elevated level of MSAFP may indicate a fetal malformation such as open Spina Bifida . Results are most accurate when the initial sample is obtained between 16 and 18 weeks gestation, although screening can be done from about 15 to 20 weeks. Designating a cutoff value to determine whether further testing is warranted involves weighing the risk of a missed abnormality versus the risk of complications from unnecessary testing. Usually, a cutoff value in the 95th to 98th percentile, or 2.0 to 2.5 times the normal pregnancy median (multiples of the median, or MOM), is used. This value is about 80% sensitive for open spina bifida and 95% sensitive for Anencephaly . False positive rates are between 2 to 5% ( Amniocentesis is eventually required in 1 to 2% of women originally screened. Lower cutoff values of MSAFP increase sensitivity but decrease specificity, resulting in more amniocenteses. Women who have been screened for fetal chromosome disorders by cell-free DNA screening should have serum screening with MSAFP alone, not with multiple marker screening. Ultrasonographyis the next step if further testing is warranted. Targeted ultrasonography with or without amniocentesis is done if no explanation can be determined with basic ultrasonography. Ultrasonography can Confirm gestational age (which may be underestimated) Detect multifetal pregnancy, fetal death, or congenital malformations In some women, ultrasonography cannot identify a cause for elevated alpha-fetoprotein levels. Some experts believe that if high-resolution ultrasonography done by an experienced operator is normal, further testing is unnecessary. However, because this test occasionally misses neural tube defects, many experts recommend further testing by amniocentesis regardless of ultrasonography results. Amniocentesiswith measurement of alpha-fetoprotein and acetylcholinesterase levels in amniotic fluid is done if further testing is needed. Elevated alpha-fetoprotein in amniotic fluid suggests A neural tube defect Another malformation (eg, omphalocele, congenital nephrosis, cystic hygroma, gastroschisis, upper gastrointestinal atresia) Contamination of the sample with fetal blood Presence of acetylcholinesterase in amniotic fluid suggests A neural tube defect Another malformation Elevated alpha-fetoprotein plus presence of acetylcholinesterase in amniotic fluid is nearly 100% sensitive for Anencephaly and 90 to 96% sensitive for open 1.Conde-Agudelo A, Kafury-Goeta AC: Triple-marker test as screening for Down syndrome: a meta-analysis.Obstet Gynecol Surv53(6):369-376, 1998. doi:10.1097/00006254-199806000-00022 2.Wald NJ, Huttly WJ, Hackshaw AK: Antenatal screening for Down's syndrome with the quadruple test.Lancet361(9360):835-836, 2003. doi:10.1016/S0140-6736(03)12680-3 3.Breathnach FM, Malone FD, Lambert-Messerlian G, et al: First- and second-trimester screening: detection of aneuploidies other than Down syndrome.Obstet Gynecol110(3):651-657, 2007. doi:10.1097/01.AOG.0000278570.76392.a6 4.Palomaki GE, Bupp C, Gregg AR, et al: Laboratory screening and diagnosis of open neural tube defects, 2019 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG).Genet Med22(3):462-474, 2020. doi:10.1038/s41436-019-0681-0 