Ch 18 - Prenatal Diagnosis and Screening

prenatal diagnosis

• known elevated risk

• usually invasive testing

• yes or no answer

prenatal screening

• no known elevated risk

• noninvasive

• not a yes or no answer

• identifies pregnancies that should have prenatal diagnosis

prenatal screening tests

• neural tube defects

• down syndrome and other aneuploidies

• integrated screening strategies

• noninvasive prenatal screening (NIPS)

• ultrasonography

screening for Neural Tube Defects (NTD)

• maternal serum alpha-fetoprotein (MSAFP) elevated in NTD at 16 weeks gestation

• elevated levels do not always mean NTD

• best when combined with ultrasonography

• AFP - fetal liver - fetal circulation - excreted through kidneys - urine/amniotic fluid - enters maternal blood via placenta

Screening for Down Syndrome and other Aneuploidies

first trimester (11-13 wks):

• maternal serum analyte screening and ultrasonographic measurement of nuchal translucency (NT)

• analytes = proteins whose low levels can indicate risk for aneuploidy

• NT = ultrasound measures fluid in soft tissue in neck (trisomy 21, 18, 13)

second trimester (18-20 wks):

• quad screen = 4 analytes tested

integrates screening strategies

combine risks determined in first and second trimester screens in a sequential manner

noninvasive prenatal screening

• cell-free fetal DNA freely floats in maternal serum (origin is placental)

• fragments are sequenced and mapped to a chromosome

• comparison to reference sequence can indicate differences in the amounts of sequences, which can indicate aneuploidy

• commonly used for Trisomy 13, 18, 21, Cfib, RhD, Tay-Sachs, sex-determination for x-linked disorders

ultrasonography screening

can be used to assess some congenital anomalies

prenatal diagnosis testing

amniocentesis and chronic villus sampling

Amniocentesis

• sample of amniotic fluid taken for analysis

• sample taken at 16-20 wks gestation

• risk to fetus

• fetal chromosome analysis (karyotype) and/or DNA analysis

• test alpha-fetoprotein in amniotic fluid (AFAFP), elevated in neural tube defects

Chorionic Villus Sampling (CVS)

• performed at 10-13 wks (early detection advantage to amniocentesis)

• fetal chromosome analysis (karyotype) and/or DNA analysis

• AFP cannot be detected this early

Laboratory prenatal chromosome analysis

mosaicism, culture failure or unexpected adverse findings

Mosaicism

• true mosaicism - different primary cultures have mosaicism

• pseudomosaicism - cells derived from single primary culture are mosaic (most likely mosaicism arose in culture)

• confined placental mosaicism

preconception genetic screening and testing

parental carrier screening and preimplantation genetic testing

parental carrier screening

identify carriers of autosomal recessive and x-linked disorders

preimplantation genetic testing

• IVF - test embryos, select healthy embryos, implant into uterus

• testing includes PCR, FISH, and CMA

• arose for couples with disease in their family who are opposed to termination of pregnancy

Concerns of PGT

• accuracy of testing on one or small number of cells

• ethical questions concerning discarded embryos