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DIAGNOSIS
Prenatal screening
SOGC Clinical Practice Guidelines – Prenatal Screening for Fetal Aneuploidy
Obstetrics: Normal and Problem Pregnancies (Gabbe) – Prenatal Genetic Diagnosis
Williams Obstetrics: Prenatal Diagnosis and Fetal Therapy
• Screening: use of specific marker(s) to identify individuals in a population at highest risk for particular disorder
◦ Condition being screened for should be severe, and results of screening should affect our management of
the pregnancy or the infant’s care after birth
◦ An accurate diagnostic test for all individuals who screen positive must be in place, in addition to
accessible intervention
◦ Markers must be maximally sensitive and specific (i.e. able to identify significant proportion of individuals
with condition and minimal number of individuals without the condition)
• Prenatal non-invasive screening tests for Down syndrome, trisomy 18, and open neural tube defects (OTNDs)
must be offered to all women for risk stratification prior to consideration of invasive diagnostic methods
• Women >40 years of age (at estimated date of delivery) can opt to undergo invasive diagnostic methods such
as CVS and amniocentesis based on age alone, without prior screening (benefits > risks)
Screening: surveying the population to identify individuals at higher risk of having a certain condition
Applies to Outcome
• Nuchal translucency (NT): sonographic visualization of increased thickness of subcutaneous fluid behind the
fetal neck above 95th percentile for fetal age; increased size of translucency from 11-14 weeks gestational age
associated with increased risk of Down syndrome, as well as other trisomies, Turner syndrome, and congenital
cardiac defects.
• Taiwan J Obstet Gynecol. 2010 Jun;49(2):133-8.
◦ Mechanism of NTrelates to:
▪ Abnormal collagen synthesis: trisomies 13, 18, 21, and Turner syndrome have altered formation of
extracellular matrix proteins such as collagen, which results in increased NT.
▪ Defects in lymphatics formation: hypothesized to be central defect leading to both NT and cardiac
defects. An underlying endothelial differentiation defect causes abnormal lymphatic vessel
formation, which in turn leads to accumulation of fluid behind neck. Cardiovascular defects may also
stem from this underlying endothelial defect.
• FTS serum biochemical markers: pregnancy-associated plasma protein A (PAPP-A) and free b-hCG
◦ Decreased PAPP-A and increased free b-hCG in patients carrying fetuses with Down syndrome
• Consideration of maternal age, nuchal translucency, and serum levels of PAPP-A and b-hCG detects 83% of
cases of Down syndrome (with 5% false positive rate)
Second trimester screening for aneuploidy
Quad screen: Maternal serum alpha fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin
(hCG), dimeric inhibin-A (DIA) measured at 15-20 weeks gestation
• Detects 77% fetuses with Down syndrome with 5.2% false positive rate
Production Down syndrome Other relations
• Increased in
maternal smoking
Unconjugated Synthesized from conversion Decreased: mechanism • Decreased with
estriol of fetal hepatic substrates in unclear but maybe due to maternal type 1
placenta: fetal immaturity of fetal adrenal diabetes and obesity
dihydroepiandrosterone cortex, fetal liver, or placenta
sulfate (DHEAS) originating
from adrenal cortex
undergoes hydroxylation in
liver → converted to estriol in
placenta → diffuses into
maternal circulation
Detection rate for Down syndrome 80-85% (3-9%) 85-90% (2-4%) 80-90% (2-7%)
(false positive rate)
Diagnostic test if screen positive Amniocentesis at 15-22 weeks Amniocentesis at 15-22 weeks
Patients in Ontario can elect to pursue integrated prenatal screening or triple/quadruple screening independently (if
prenatal screening is not elected to be done until after 14 weeks). In most centers, quadruple screening has replaced
triple screening. Stepwise and contingent sequential screenings are not options available in Ontario.
Prenatal diagnosis
SOGC Clinical Practice Guidelines – Canadian Guidelines for Prenatal Diagnosis: Genetic Indications for Prenatal Diagnosis
Obstetrics: Normal and Problem Pregnancies (Gabbe)
Prenatal genetic diagnosis: involves an invasive procedure (amniocentesis, chorionic villus sampling, or fetal blood
sampling) to conduct subsequent cell culture and chromosomal evaluation
• Relative contraindications:
vaginal bleeding, extreme uterine
anteflexion or retroflexion,
genital tract infection