Porth's Essentials of Pathophysiology, 4e

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Genetic and Congenital Disorders

C h a p t e r 6

Fetoscope

Syringe for collecting chorionic villus sample

Ultrasonography transducer

Transabdominal amniocentesis

Cordocentesis

Umbilical cord

Amniotic cavity

Transcervical chorionic villus sampling

Catheter

Chorion frondosum

Vagina

Cervix Rectum

FIGURE 6-15. Methods of prenatal screening.

implantation in the uterine wall. It increases rapidly in the first 8 weeks of gestation, declines steadily until 20 weeks, and then plateaus. The single maternal serum marker that yields the highest detection rate for Down syndrome is an elevated level of hCG. Unconjugated estriol is produced by the placenta from precursors provided by the fetal adrenal glands and liver. It increases steadily throughout pregnancy to a higher level than that normally produced by the liver. Unconjugated estriol levels are decreased in Down syn- drome and trisomy 18. Other maternal serum markers include pregnancy- associated plasma protein A (PAPP-A) and inhibin A. 62 PAPP-A, which is secreted by the placenta, has been shown to play an important role in promoting cell dif- ferentiation and proliferation in various body systems. In complicated pregnancies, the PAPP-A concentration increases with gestational age until term. Decreased PAPP-A levels in the first trimester (between 10 to 13 weeks) have been shown to be associated with Down syndrome. When used along with maternal age, free β -hCG, and ultrasound measurement of nuchal trans- lucency, serum PAPP-A levels can reportedly detect

85% to 95% of affected pregnancies with a false- positive rate of approximately 5%. 62 Inhibin A, which is secreted by the corpus luteum and fetoplacental unit, is also a maternal serum marker for fetal Down syndrome. 63 Non-Invasive Prenatal Testing (NIPT) Circulating cell free DNA (cf-DNA) fragments are short fragments of DNA found in the blood. During pregnancy, there are cf-DNA fragments from both the mother and fetus in maternal circulation. It is pos- sible to analyze cf-DNA from the maternal blood to detect common fetal trisomies such as Down syndrome as early as 10 weeks. Non-invasive prenatal testing using cf-DNA offers tremendous potential as a screen- ing tool due to its increased accuracy over maternal serum markers and the nuchal translucency tests. 64 The recent and rapid adoption of non-invasive prenatal screening in high-risk pregnancies in the United States suggests that NIPT may change the standard of care for genetic screening (ACOG 2013). 11