Prenatal Maternal Serum Screening for Neural Tube Defects, Down
Syndrome, Trisomy 18
Specimen Requirements
Prenatal maternal serum screening consists of measuring four chemical markers present in the mother's blood during pregnancy:
alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), unconjugated
estriol (uE3), and dimeric inhibin A (DIA). Abnormal levels of these chemicals
may indicate increased risk for certain birth defects and genetic diseases.
Approximately 5% of all pregnancies tested will have an abnormal screening test
requiring additional diagnostic testing. Only a small number of these
pregnancies are affected with a birth defect or genetic disease. Inaccurate
pregnancy dating (gestational age) and the presence of twins or other multiples
can cause an abnormal screening result. Pregnancy dating by ultrasound will
ensure the most accurate test result. Estimation of gestational age by
ultrasound using biparietal diameter is optimal because it reduces the initial
screen positive rate and increases detection of neural tube defects. Use of
fetal femoral length dating potentially decreases the detection of Down
syndrome. Genetic counseling and prenatal diagnostic testing should be
considered with any positive maternal serum screening result.
Alpha-fetoprotein (AFP) is a protein produced by the
fetal liver and yolk sac. The function of AFP during fetal development has not
been clearly defined. AFP is present in high concentration in fetal blood and
declines rapidly in newborn serum after birth. AFP is present in lower
concentration in fetal urine and is detectable in amniotic fluid. During
pregnancy, there are detectable levels of AFP in maternal serum. Open neural
tube defects and other open fetal malformations with exposed membranes and blood
vessel surfaces allow excessive AFP to transudate into amniotic fluid. In the
presence of open fetal defects, increased levels of AFP in maternal serum may
result from increased levels of AFP in amniotic fluid.
Human chorionic gonadotropin (hCG) is a glycoprotein
hormone synthesized by the placenta and is necessary for early pregnancy
maintenance. HCG appears in maternal serum about 6-8 days after conception and
reaches a peak around 10 weeks. During the second trimester, hCG declines
progressively to a fairly constant level at 18-20 weeks.
Unconjugated estriol (uE3) is a steroid hormone
produced in the placenta using precursor steroids from the fetus and mother. The
hormonal functions of uE3, a relatively weak estrogen, are not well understood.
During pregnancy, estrogens are thought to maintain proper functioning of the
uterus, soften cervix and aid lactation. Maternal serum uE3 levels rise above
non-pregnancy levels by 7-9 weeks gestation and continue to increase throughout
pregnancy. Low levels of maternal uE3 in the third trimester have been reported
in newborns with low birth weight and have been found to indicate fetal
distress.
Dimeric inhibin A (DIA) is a glycoprotein hormone
synthesized by the corpus luteum and placenta in pregnancy. The specific
role of DIA during pregnancy has not been determined. Maternal serum DIA
levels increase during the first trimester, then decline after 10 weeks and
remain stable between 15-25 weeks. DIA levels rise again after 25 weeks to
reach a peak at term.
| |
AFP |
hCG |
UE3 |
DIA |
Risk Cutoff |
Detection |
| NTD |
High |
--- |
--- |
--- |
>2.0 MOM |
85% |
| Down Syn |
Low |
High |
Low |
High |
>1/270 |
70% |
| Trisomy 18 |
Low |
Low |
Low |
--- |
>1/100 |
60% |
Neural Tube Defect Screening: Elevated
Maternal serum AFP levels indicate an increased risk for open spina bifida
and anencephaly. Other risk factors include family history of neural tube
defects, certain maternal drug exposures, and maternal insulin-dependent
diabetes. More definitive tests such as high-resolution ultrasound, amniotic
fluid AFP, and acetycholinesterase are recommended when there is an increase
risk for an open neural tube defect. Adverse pregnancy outcomes associated
with elevated maternal serum AFP are prematurity, growth retardation, low
birth weight, and fetal demise.
Down Syndrome Screening: Maternal serum screening for
Down syndrome utilizes the maternal age specific risk and second trimester
levels of AFP, hCG, uE3, and DIA to calculate a risk estimate for each
pregnancy. A positive screen for Down syndrome is reported when the risk is
greater than or equal to 1:270. Risks less than 1:270 are reported as a negative
screen.
Trisomy 18 Screening: The estimated trisomy 18 risk for
each pregnancy is calculated based on the maternal age risk and the levels of
AFP, hCG, and uE3. A positive screen for trisomy 18 is reported when the risk is
greater than or equal to 1:100.
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