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
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.
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
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
Used for detection of: n of: • ONTD • Down syndrome • trisomy 18 • Smith-Lemli-Opitz syndrome
HyperglycosylatedhCGexcreted • 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.
Screening tests that combine first andsecond-trimester markers • Integrated • Sequential – Stepwise sequential – Contingent sequential
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 .
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
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
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%)
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, • abruptioplacentae, and preeclampsia. • no management protocol has been demonstrated to improve outcome in these cases.
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
Unexplained Elevated Human Chorionic GonadotropinLevels unexplained elevated hCG(>2.0 MoM) is associated with an increased risk for preeclampsia,pretermbirth, low birth weight, fetal demise, and possibly hypertension Low Second-Trimester Maternal Serum Estriol Low maternal serum unconjugatedestriol levels have been linked to adverse pregnancy outcomes Very low or absent estriollevels 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,adrenocorticotropindeficiency,hypothalamiccorticotropindeficiency, and anencephaly.
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.
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 mosaicismfor chromosome 16 has been reported to be associated with extremely high levels of both analytes, as well as with similarly poor outcomes.
Abnormal Quad Screen Markers ↑edinhibin A + ↑edhCG and/or AFP (>2.0MoM): Consider: • Uterine artery Dopplers at @18-20 weeks • Close surveillance for IUGR and preeclampsia • Non-stress tests for cases with IUGR or preeclampsia
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
Down Syndrome Screening forDizygotic 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 31-33 years is the equivalent risk of a 35-year old woman with a singleton
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%.