Prenatal diagnosis Flashcards
What is an EIF and how commonly do they occur?
An EIF is a small echogenic area appearing within the fetal cardiac ventricle that has a sonographic brightness equivalent to that of bone, believed to represent a microcalcification of the papillary muscle. present a microcalcification of the papillary muscle. An EIF is a common finding during a routine second-trimester fetal anatomic survey and is identified in 3% to 5% of normal fetuses. The prevalence of EIF may vary according to maternal ethnicity (30% of fetuses of Asian mothers in one study).
What are the clinical implications of an isolated EIF?
An EIF is not considered a structural or functional cardiac abnormality. It has not been associated with cardiac malformations in the fetus or newborn. The only reported clinical implication is an increased risk of trisomy 21.When an EIF is identified, an experienced provider should perform a detailed fetal anatomic survey to assess for the presence of structural malformations and other sonographic markers of aneuploidy. In addition, the physician should perform an assessment of other risk factors, including maternal age, results of other screening or diagnostic tests, and family history. Most EIFs are isolated and occur in otherwise low-risk pregnancies.
When an isolated EIF is detected, how does counseling differ for women at increased risk for fetal aneuploidy and for women with normal aneuploidy screening results?
All patients, regardless of ultrasound findings, should be offered prenatal screening for aneuploidy and should have the option of invasive diagnostic testing. Counseling for a woman after prenatal identification of EIF should be guided by presence of other sonographic markers or structural abnormalities, maternal serum screening for risk of Down syndrome (if performed), and maternal age. If an isolated EIF is detected in a woman who has already had an invasive diagnostic testÌ¢‰â‰Ûand the fetal karyotype is knownÌ¢‰â‰Ûshe can be reassured that the finding is considered a normal variant.
What is the association between EIF and T21?
Meta-analyses - risk of trisomy 21 was increased 1.8- to 5.4-fold by the finding of an isolated EIF. Recently, another meta-analysis similarly identified a 2.9 likelihood ratio (LR) for isolated EIF, when defined as no major abnormalities and no evidence of ventriculomegaly, increased nuchal skinfold thickness, echogenic bowel, pyelectasis, short humerus, or short femur.
How should a woman with an isolated EIF be followed throughout pregnancy?
Because an isolated EIF does not represent a cardiac abnormality, fetal echocardiography is not needed and no specific follow-up is recommended. Follow-up should be performed based on the presence of other clinical indications or the results of the patientÌ¢‰â‰ã¢s prenatal screening and/or diagnostic testing.
What are the ultrasound features of triploidy?
Placental abnormalities of hyditaform degeneration are present in almost all cases in which the extra haploid set of chromosomes are paternal but much less common if maternal.
The placenta may appear thickened or demonstrate cystic changes on U/S but these changes are variable. Common fetal features include holoprosencephaly and hydrocephalus (50%), agenesis of the CC, NTD (25%), facial abnormalities (low set ears, micrognathia, cleft palate), IUGR/small abdomen, single umbilical artery, syndactyly of the 3rd and 4th fingers, cardiac anomalies (60%), GU anomalies.
What are the differences between Type I and Type II triploidy?
Type I is paternal with a large cystic placenta, symmetric IUGR, elevated maternal hCG, AFP and inhibin.
Type II is maternal with small non-cystic placenta, low levels of hCG and estriol.
What does this karyotype mean: 45XX -14,-21, +t(14,21)?
Robertsonian translocation, present in about 4 percent of Down syndrome patients.
Translocation is usually between 21q and another acrocentric chromosome - usually 14 and 22.
A carrier involving 14 and 21 has only 45 chromosomes - one chr 14 and one chr 21 are missing, and are replaced by the translocation chromosome t(14q21q).
6 possible types of gametes, 3 are nonviable, 1 is normal one, is balanced and 1 is unbalanced (has both chr 21 and the translocated chromosome).
15 percent of progeny of mothers are affected. Less if father is affected.
What genetic abnormalities are associated with advanced paternal age?
Achondroplasia, thanatophoric dysplaisa, OI, Marfan’s
T21 - NT, PAPP-A, f-BhCG
Incr NT, low PAPP-A, high BhCG(Median MoM - PAPP-AP 0.38, BhCG 1.83)
T18 - NT, PAPP-A, f-BhCG
Incr NT, low PAPP-A, low BhCG
Pregnancy loss < 24w
Incr NT, very low PAPP-A, very low BhCG
Congenital heart defect
Incr NT, normal PAPP-A, normal BhCG
Most powerful marker for general population screening for T21
NT sonography
When can NT be performed?
Between 10 3/7 and 13 6/7 weeks gestationCRL 36 - 84 mm
Criteria for NT measurement
- Fetus in midsagittal plane, ideally with spine down2. Only fetal head, neck, and upper thorax fill the viewable area3. Fetal neck should be neutral - not hyperflexed or hyperextended4. Skin at the fetal back clearly differentiated from underlying amniotic membrane5. Measurement calipers placed on inner borders of echolucent space, perpendicular to long axis of fetus6. US and transducer setting optimized to ensure clarity of the image and borders of NT. May require TVUS
FASTER trial results for NT sonography
Multicenter prospective trial36,306 pts from general population had 1st trimester NT sonoDetection rate 70% at 11w, 64% at 13w, for a 5% false + rate
Sensitivity of BhCG + PAPP-A + maternal age for T21
60% with a 5% FP rate
Sensitivity of NT + BhCG + PAPP-A + maternal age for T21 (FASTER)
11w - 87%12w - 85%13w - 82%(5% FP rate)
Does 1st trimester combined screening have a significantly better performance than 2nd trimester quad for T21?
Only when performed at 11w - 87% vs 81%, at 5% FP
Which test has the lowest false + rate for T21 - 1st trimester combined or quad?
1st trimester combined
What is a septated cystic hygroma?
The NT space is enlarged, extending along the entire length of the fetus, and septations are clearly visible
Risk of fetal aneuploidy with septated cystic hygroma? Which ones?
50%Most cases T21, then 45,X and T18
Among euploid cystic hygroma cases, risk of major structural fetal malformation? Which ones?
50%Most cases cardiac abnl, also skeletal dysplasia
Risk of fetal malformation or demise with septated cystic hygroma vs simple incr NT
Septated CH - 5x more aneuploid, 12x more cardiac abnl, 6x more fetal or neonatal demise
If a simple NT >/= ___ is noted, then CVS should be offered bc the minimum risk of aneuploidy is 1 in 6
NT >/= 3 mm
Percent of T21 fetuses w/ nonvisualization of the nasal bone (Cicero 2001)
70% (43/59), vs 0.5% of unaffected fetuses (3/603)
Sensitivity of NB + NT + BhCG + PAPP-A + maternal age for T21
85% for 1% FP rate in Cicero 200167% for 2.8% FP rate in Cicero 2003
Technique for imaging nasal bone
- Midsagittal plane with perfect fetal profile2. Fetal spine posterior, slight neck flexion3. 2 echogenic lines - superficial is nasal skin, deeper is nasal bones4. Deeper echogenic line representing nasal bone should be more echolucent at its distal end5. Care taken not to have US beam parallel to plane of NB - may appear absent
How often is absent NB seen in general population? High-risk population?
15%, 50%
What is the ductus venosus abnl in aneuploidy and cardiac malformations?
Reversed flow at time of atrial contraction
How often is abnl DV seen with aneuploidy? With nl fetuses?
Aneuploidy - 60-90%Normal - 3-20%
Pitfalls of 1st trimester DV screening
- DV may be as small as 2 mm at 10-14w2. If Doppler gate is placed too proximally near the umbilical sinus, venous flow may obscure absence of flow during atrial contraction3. If gate too distal into IVC, may erroneously dx reversed atrial contraction flow, which is common in IVC
TV regurgitation in nl vs aneuploid fetuses
Seen in only 4% of chromosomally nl fetuses, vs 70% of T21 and 33% of T18
How to perform 1st trimester tricuspid regurgitation evaluation
- Fetus oriented so chest wall is anterior2. Fetal heart insonated parallel to ventricular septum3. Pulsed-Doppler gate of 3 mm placed across tricuspid valve4. Ensure that the angle to the direction of flow is as close to zero as possible5. Tricuspid regurgitation is present if a regurgitant jet of at least 60 cm/sec extends to over half of systole
NT screening in multiple gestations
NT measurements are similar btw singleton and twin pregnancies, implying that T21 detection rates should be similarFalse + rate in monochorionic twins may be higher bc of TTTS, for example
Is it appropriate to use a single millimeter cutoff to define a nl NT?
Per Callen, no. Mean NT measurements increase by approximately 15-20% each week from 10-14w gestation. More appropriate would be 95th percentile for GA or MoM. But must integrate other data, such as maternal age and serum marker results.
Definition of, complications from early amniocentesis
Before 15w - incr fetal loss, fetal club foot, procedure failure
Most efficient method of aneuploidy screening
1st trimester NT+PAPP-A, + 2nd trimester AFP, hCG, E3, inhibinIf NT unavailable, then serum only test is reasonable (PAPP-A then quad)
ACOG Guidelines for use of cell-free fetal DNA
Maternal age Ì¢‰Û¡å´35 years at deliveryPresence of sonographic findings associated with fetal aneuploidyHistory of previous pregnancy with fetal trisomyParental balanced robertsonian translocation with increased risk of trisomy 21 or 13Screen-positive result for aneuploidy on screening tests such as the first trimester combined test, integrated test, sequential test, or quadruple test
Sensitivity and specificity of cffDNA
Detection rate >98 percent and false positive rate <0.5 percent
In the largest study to date (8/13) how often did cffDNA fail to give a result?
0.80%
Per ACOG, risk of fetal loss with amniocentesis
1/300-1/500
Trisomy 22
Trisomy 22 is found in only 1 in 30-50 000 livebirths; however, it is one of the most common chromosomal abnormalities found in early spontaneous miscarriages, second in frequency only to trisomy 16.
Findings associated with single umbilical artery
Cardiac (AVSD, coarc, TGA, TOF)
GU (hydronephrosis, renal pelvis dilatation)
GI
Aneuploidy (2.6% if isolated, 42% if major anomaly)
IUGR
Downfalls for US in fetal anomalies
Dependent on: Operator Patient Window Anomaly Tissue differentiation and slicing not as good as MR Not so good for airway/oral
What are isolated choroid plexus cysts and how common are they?
A choroid plexus cyst is a small fluid-filled structure within the choroid of the lateral ventricles of the fetal brain. Sonographically, choroid plexus cysts appear as echolucent cysts within the echogenic choroid. May be single or multiple, unilateral or bilateral, and most often are less than 1 cm in diameter. Choroid plexus cysts are identified in approximately 1% to 2% of fetuses in the second trimester and they occur equally in male and female fetuses.
What are the major clinical implications of an isolated choroid plexus cyst?
When a choroid plexus cyst is identified, the presence of structural malformations and other sonographic markers of aneuploidy should be assessed with a detailed fetal anatomic survey performed by an experienced provider. Detailed examination of the fetal heart (4-chamber view and outflow tracts view) and hands (for ‰ÛÏclenching‰Û or other abnormal positioning) should be included, as well as fetal biometry for assessment of intrauterine growth restriction. If no other sonographic abnormalities are present, the choroid plexus cyst is considered isolated.A choroid plexus cyst is not considered a structural or functional brain abnormality. Most choroid plexus cysts are isolated and occur in otherwise low-risk pregnancies.
What is the association between choroid plexus cysts and aneuploidy?
The only association of some significance between an isolated choroid plexus cyst and a possible fetal problem is with trisomy 18. Choroid plexus cysts are present in 30% to 50% of fetuses with trisomy 18. When a fetus is affected by trisomy 18, multiple structural anomalies are almost always evident, including structural heart defects, clenched hands, talipes deformity of the feet, growth restriction, and polyhydramnios. When a structural anomaly is present in addition to choroid plexus cysts, the probability of trisomy 18 is 37%.In the absence of associated sonographic abnormalities, the likelihood of trisomy 18 is extremely low in otherwise low-risk pregnancies. SBased on a meta-analysis of 14 studies published before 2000, Ghidini et al suggested utilization of a composite (+) likelihood ratio of 7.09 (95% CI, 3.97-12.18). A large, single-center cohort study (N=1111 cases of isolated choroid plexus cyst) published in 2008 reported much lower risk.
When an isolated choroid plexus cyst is detected, how is counseling different for women with a normal screen versus those whose screening indicates increased risk?
Counseling for a woman after prenatal identification of a fetal choroid plexus cyst should be guided by the presence or absence of other sonographic markers or structural abnormalities, results of maternal screening for risk of trisomy 18 (if performed), and maternal age.In women who screen negative for trisomy 18 and in whom no other fetal structural abnormalities are visualized on a detailed ultrasound, the finding of an isolated choroid plexus cyst does not require additional genetic testing. Some experts suggest that it is unnecessary for a physician to discuss such a finding with a patient because it can be considered a normal variant. If it is discussed, the patient can be reassured about the extremely low risk of trisomy 18. Ultrasound characteristics of choroid plexus cysts (size, complexity, laterality, and persistence) should not be used to further modify risk because these factors do not significantly impact the likelihood of trisomy 18. The presence of a choroid plexus cyst does not alter the risk of trisomy 21, and the finding should not be used to modify a patient‰Ûªs risk of trisomy 21.
Trisomy 22
Trisomy 22 is found in only 1 in 30‰ÛÒ50 000 livebirths; however, it is one of the most common chromosomal abnormalities found in early spontaneous miscarriages, second in frequency only to trisomy 16.
