1. Second-trimester maternal serum screening

2. Risks and benefits associated with diagnostic procedures
Counseling for all patients
Information about the screening tests offered
– Detection rate
– False-positive rate
– Advantages
– Disadvantages
– Limitations
Risks and benefits associated with diagnostic procedures

3. Goal for screening tests:
High detection rates
Low false-positive rates
Provide patients with the diagnostic options
they might want to consider
Screening and invasive diagnostic testing should
be available to all women who present for prenatal care before 20 weeks of gestation regardless of maternal age.

4. First trimester screening with both NT and biochemical markers is an effective screening test for the general population, and is comparable to the 2nd trimester quadruple screen with the additional advantage of earlier
pregnancy terminations if desired.
Neural tube defect screening should be offered in the second trimester to women who elect only first trimester screening for aneuploidy

5. Second Trimester Quad Screen 15-22 weeks gestation
AFP, hCG, uE3, inhibin A
81% DR at a 5% positive screen rate
Good for women who don’t want 1st
trimester screening or who register for
care after first trimester

6. Used for detection of: n of:
ONTD
Down syndrome
trisomy 18
Smith-Lemli-Opitz syndrome

7. Hyperglycosylated hCG excreted
in maternal urine has been tested as a marker for Down syndrome
With the addition of extra markers, the potential benefit must be balanced against the cost.

8. Screening tests that combine first and second-trimester markers
Integrated
Sequential
– Stepwise sequential
– Contingent sequential

9. Integrated Screen(9O-96%)
Measurements during both trimesters are combined with maternal age to provide a
single estimate of a woman’s risk of
having a pregnancy affected by Down syndrome
1st trimester: PAPP-A and NT
2nd trimester: AFP, uE3, hCG, and inhibin-A
Offer when CVS is not available .

10. Sequential Screening Tests
Patient is informed of the first-trimester screening result
Allows patients the option to have CVS
– Stepwise Sequential Screening
– Contingent Sequential Screening
88-94% DR at a 5% positive screen rate

11. Stepwise Sequential Screen
1st trimester: NT, PAPP-A + maternal age(90%-95%)
Risk Assessment
Positive1%
Negative(99%)
Quad screen
CVS
Risk based on maternal
age, 1st trimester + quad
screen

12. Contingent Sequential Screen(88-94%)
1st trimester: NT, PAPP-A + maternal age
screen positive → offer CVS(1%)
intermediate → offer quad screen(15%)
screen negative → no further testing(84%)

13. ABNORMAL SECOND-TRIMESTER MATERNAL SERUM MARKERS IN PREGNANCIES WITH A NORMAL KARYOTYPE
Unexplained Elevated Maternal Serum α-Fetoprotein(2.5MOM)
Ultrasound
90% r/o spinal lesions
100% r/o anencephaly
VWD reduced with normal scan
If MSAFP >4.0 MoM and NL U/S Offer invasive testing
ONTD screening
fetal growth restriction,
fetal death,
prematurity,
oligohydramnios,
abruptio placentae, and preeclampsia.
no management protocol has been demonstrated to improve outcome in these cases.

14. Maternal weight Gestational age Race or ethnicity Diabetes
Several factors influence the maternal serum AFP level and are taken into consideration when calculating the AFP MoM:
Maternal weight
Gestational age
Race or ethnicity
Diabetes
Multifetal gestation

15. Unexplained Elevated Human Chorionic Gonadotropin Levels
hCG (>2.0 MoM) is associated with an increased risk for preeclampsia,preterm birth, low birth weight, fetal demise, and possibly hypertension
Low Second-Trimester Maternal Serum Estriol
Low maternal serum unconjugated estriol levels have been
linked to adverse pregnancy outcomes
Very low or absent estriol levels of 0.0 to 0.15 MoM suggest biochemical abnormalities of the fetus or placenta, including placental steroid
sulfatase deficiency, Smith-Lemli-Opitz syndrome, congenital adrenal hypoplasia,adrenocorticotropin deficiency,hypothalamiccorticotropin deficiency, and anencephaly.

16. Smith-Lemli-Opitz syndrome
occurs in approximately 1/60,000 pregnancies and is an autosomal recessive disorder
defect in 3β-hydroxysteroid-Δ7-reductase, altering cholesterol synthesis and resulting in low cholesterol levels and the accumulation of the cholesterol precursor 7-dehydrocholesterol in blood and amniotic fluid.
Smith-Lemli-Opitz syndrome is characterized by low birth weight, failure to thrive, and moderate to severe mental retardation.
It is associated with multiple structural anomalies,
including syndactyly of the second and third toes, microcephaly, ptosis, and a typical-appearing facies.
Undermasculinization of the genitalia, including complete sex reversal, can be
seen in male fetuses.

17. Elevated Human Chorionic Gonadotropin and Maternal Serum α-Fetoprotein
The combination of elevated MSAFP and hCG levels occurs
rarely but may have an overall pregnancy complication rate
exceeding 50%.
preeclampsia, preterm birth, growth restriction, placental
abnormalities, and fetal death
Confined placental mosaicism for chromosome 16 has been reported to be associated with extremely high levels of both analytes, as well as with similarly poor outcomes.

18. Abnormal Quad Screen Markers
↑ed inhibin A + ↑ed hCG and/or AFP (>2.0MoM):
Consider:
Uterine artery Dopplers weeks
Close surveillance for IUGR and preeclampsia
Non-stress tests for cases with IUGR or preeclampsia

19. Down Syndrome Screening for Monozygotic Twins
Risk for aneuploidy is the same as for singleton
Average of the two NT measurements can be used to calculate the pregnancy risk
An enlarged NT and/or significantly discordant measurements between twins may be markers for adverse outcomes independent of aneuploidy risk

20. Down Syndrome Screening for Dizygotic Twins (> 70% of twins)
Each fetus carries an independent risk for Down syndrome
Age-related risk for having 1 aneuploid fetus is higher than that of a woman with a singleton pregnancy
Individual NT measurements can be used to
calculate the fetus-specific risk
A maternal age of years is the equivalent risk of a 35-year old woman with a singleton

21. Screening Tests in Twins
For twins, however, the value and accuracy of serum screening is much less certain because the contribution of an abnormal fetus will, on average, be brought closer to the normal mean by an unaffected co-twin.
This tends to decrease the overall screening sensitivity. Screening,
however, can be useful nonetheless.
At present, there is no standard agreement on the MSAFP elevation that warrants further evaluation in twins.
Some centers use a cutoff of 4.0 MoM, which would identify approximately
60% of fetuses with open spina bifida, but this has approximately an 8% incidence of false-positive results.
Other centers use a cutoff of 4.5 MoM, which has a sensitivity of approximately 50%.