2 Risks and benefits associated with diagnostic procedures Counseling for all patientsInformation about the screening tests offered– Detection rate– False-positive rate– Advantages– Disadvantages– LimitationsRisks and benefits associated with diagnostic procedures
3 Goal for screening tests: High detection ratesLow false-positive ratesProvide patients with the diagnostic optionsthey might want to considerScreening and invasive diagnostic testing shouldbe 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 earlierpregnancy 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 A81% DR at a 5% positive screen rateGood for women who don’t want 1sttrimester screening or who register forcare after first trimester
6 Used for detection of: n of: ONTDDown syndrometrisomy 18Smith-Lemli-Opitz syndrome
7 Hyperglycosylated hCG excreted in maternal urine has been tested as a marker for Down syndromeWith the addition of extra markers, the potential benefit must be balanced against the cost.
8 Screening tests that combine first and second-trimester markers IntegratedSequential– Stepwise sequential– Contingent sequential
9 Integrated Screen(9O-96%) Measurements during both trimesters are combined with maternal age to provide asingle estimate of a woman’s risk ofhaving a pregnancy affected by Down syndrome1st trimester: PAPP-A and NT2nd trimester: AFP, uE3, hCG, and inhibin-AOffer when CVS is not available .
10 Sequential Screening Tests Patient is informed of the first-trimester screening resultAllows patients the option to have CVS– Stepwise Sequential Screening– Contingent Sequential Screening88-94% DR at a 5% positive screen rate
11 Stepwise Sequential Screen 1st trimester: NT, PAPP-A + maternal age(90%-95%)Risk AssessmentPositive1%Negative(99%)Quad screenCVSRisk based on maternalage, 1st trimester + quadscreen
13 ABNORMAL SECOND-TRIMESTER MATERNAL SERUM MARKERS IN PREGNANCIES WITH A NORMAL KARYOTYPE Unexplained Elevated Maternal Serum α-Fetoprotein(2.5MOM)Ultrasound90% r/o spinal lesions100% r/o anencephalyVWD reduced with normal scanIf MSAFP >4.0 MoM and NL U/S Offer invasive testingONTD screeningfetal 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 weightGestational ageRace or ethnicityDiabetesMultifetal 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 hypertensionLow Second-Trimester Maternal Serum EstriolLow maternal serum unconjugated estriol levels have beenlinked to adverse pregnancy outcomesVery low or absent estriol levels of 0.0 to 0.15 MoM suggest biochemical abnormalities of the fetus or placenta, including placental steroidsulfatase 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 disorderdefect 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 beseen in male fetuses.
17 Elevated Human Chorionic Gonadotropin and Maternal Serum α-Fetoprotein The combination of elevated MSAFP and hCG levels occursrarely but may have an overall pregnancy complication rateexceeding 50%.preeclampsia, preterm birth, growth restriction, placentalabnormalities, and fetal deathConfined 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 weeksClose surveillance for IUGR and preeclampsiaNon-stress tests for cases with IUGR or preeclampsia
19 Down Syndrome Screening for Monozygotic Twins Risk for aneuploidy is the same as for singletonAverage of the two NT measurements can be used to calculate the pregnancy riskAn 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 syndromeAge-related risk for having 1 aneuploid fetus is higher than that of a woman with a singleton pregnancyIndividual NT measurements can be used tocalculate the fetus-specific riskA 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 approximately60% 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%.