Transcript Prenatal dx - Care of Children

Prenatal dx
• A 36-year-old primigravida at 20 weeks’ gestation presents to
her obstetrician’s office with a complaint of leaking fluid.
Sonographic examination performed confirms markedly
decreased fluid, and midtrimester rupture of membranes is
suspected. The patient elects to continue her pregnancy, and
minimal amnionic fluid is present around the fetus. At term,her
fetus is born with a right-sided clubbed foot.This is an
example of which of the following?
• a. Sequence
• b. Disruption
• c. Deformation
• d. Malformation
• deformation- by which a fetus develops abnormally becauseof
extrinsic mechanical forces imposed by the uterine envi-ronment.
• deformation- by which a fetus develops abnormally because of
extrinsic mechanical forces imposed by the uterine envi-ronment.
• The finding seen below was identified prenatally during sonographic
examination and is an example of which of the following?
a. Syndrome
b. Disruption
c. Association
d. Malformation
disruption, which is a more severe
change in form or function that occurs
when genetically normal tissue is
modified as theresult of a specific insult
disruption, which is a more severe change in form or function that occurs when
genetically normal tissue is modified as theresult of a specific insult
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The infant shown below was also born with a cleft palate. These findings are
consistent with which of the following processes?
a. Syndrome
b. Sequence
c. Association
d. Chromosome abnormality
A sequence describes
anomalies that all developed
sequentially from one initial insult.
An example is the Pierre-Robin
sequence in which micrognathia
A sequence describes anomalies that all developed sequentially from one initial
insult.An example is the Pierre-Robin sequence in which micrognathia
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A pregnant 25-year-old postdoctoral student presents for genetic counseling
following a multiple markerscreen that revealed an increased risk for an
openneural-tube defect and trisomy 18. She is fromFrance and her husband
s from Great Britain. Hermedical history is significant for a seizure disorder
well controlled on phenytoin. Which of the followingis NOT an expected
possible contributing factor inher elevated risk for an open neural-tube
defect
a. Ethnicity
b. Medication exposure
c. Chromosome abnormality
d. None of the above
gentic
Family history—multifactorial inheritance
MTHFR mutation—677C→T
Syndromes with autosomal recessive inheritance—
Meckel Gruber, Roberts, Joubert, Jarcho-Levin,
HARDE (hydrocephalus-agyria-retinal dysplasiaencephalocele)
Aneuploidy—trisomy 13 and 18, triploidy
Environmental Exposures
Diabetes—hyperglycemia
Hyperthermia—hot tub or sauna, fever (controversial)
Medications—valproic acid, carbamazepine, coumadin,
thalidomide, efavirenz
Geographical—Ethnicity,
Diet, and Other Factors
United Kingdom, India, China, Egypt, Mexico, Southern
Appalachian United States
• What is the recurrence risk for an open neuraltubedefect after a couple has had one child born with
anencephaly?
• a. 3% to 5%
• b. 10%
• c. 25%
• d. Unknown
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The recurrence risk is approxi-mately 3 to 5 percent if a couple has previously
had a child with either anencephaly or spina bifida, 5 percent if either parent
was born with an NTD, and as high as 10 percent if a couple has two affected
children. Importantly, almost 95 percent of NTDsdevelop in the absence of a
family history
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• Other risk factors for NTDs include hyperthermia, medi-cations that
disturb folic acid metabolism, and hyperglycemia from insulin-dependent
diabetes
• Polymorphisms in the methylene tetrahydrofolate reductase gene, which
leads to impaired homocysteine and folate metabolism, have been associated with increased risk for anencephaly and spina bifida, aswell as for
cardiac malformations (Aneji, 2012; Harisha, 2010;Munoz, 2007; Yin,
2012)
• Four-milligram folic acid supplementation
beforeconception and in the first trimester of
pregnancywould be most indicated in which of the
following scenarios?
• a. Maternal pregestational diabetes
• b. A personal history of open neural-tube defect
• c. Maternal valproic acid use for seizure disorder
• d. Maternal paroxetine use for depression
• Most women at increased risk for NTDs benefit from 4 mg
folic acid taken daily before conception and through the first
trimester. This is particularly important if a woman has one or
more prior affected children or if either the pregnant woman
or her partner has such a defect.
• Folic acid supplementation may not decrease the risk for
NTDs in those with valproic acid exposure, pregestational
diabetes, first-trimester fever or hot tub exposure, or defects
associated with a genetic syndrome (American College of
Obstetricians and Gynecologists, 2013b
• Which of the following maternal factors does not affect the maternal
serum alpha fetoprotein (AFP) multiples of the median calculation?
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a. Race
b. Parity
c. Weight
d. Gestational age
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1. Maternal weight—The AFP concentration is adjusted forthe maternal volume of
distribution.
2. Gestational age—The maternal serum concentrationincreases by approximately 15 percent
per week duringthe second trimester (Knight, 1992). In general, the MoM should be
recalculated if the biparietal diameter differs fromthe stated gestational age by more than 1
week.
3. Race/ethnicity—African American women have at least10-percent higher serum AFP
concentrations but are at lower risk for fetal NTDs.
4. Diabetes—Serum levels may be 10 to 20 percent lower inwomen with insulin-treated
diabetes, despite a three- to fourfold increased risk for NTDs (Greene, 1988; Huttly, 2004).
There is controversy whether sremains necessary or if results should apply to all types of
diabetes (Evans, 2002; Sancken, 2001; Thornburg, 2008).
5. Multifetal gestation—Higher screening threshold values are used in twin pregnancies
(Cuckle, 1990). At Parkland Hospital, an AFP level is considered elevated in a twin pregnancy if greater than 3.5 MoM, but other laboratories use4.0 or even 5.0 MoM.
• Which of the following is NOT an indication for
sonographic evaluation of an elevated maternal serum
AFP level result?
• a. Determination of fetal sex
• b. Estimation of gestational age
• c. Determination of fetal number
• d. Documentation of fetal viability
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Your patient has a 1:100 risk for a fetal open neuraltube
defect based on serum screening at 18 weeks’
gestation. She undergoes targeted sonographic
examination, which documents a singleton fetus and
a marginal placenta previa. No fetal abnormalities
are detected. Following this examination, how
should she be counseled regarding her fetus’s risk for
having an open neural-tube defect?
a. Reduced by 25%
b. Reduced by 50%
c. Reduced by 95%
d. Unchanged from the 1% risk
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More than 25 years ago, Nicolaides and colleagues (1986)
described frontal bone scalloping—the lemon sign, and anterior curvature of the cerebellum with effacement of the cisterna
magna—the banana sign—in second-trimester fetuses with
open spina bifida (Fig. 14-4). These investigators also frequently
noted a small biparietal diameter and ventriculomegaly in such
cases. Watson and coworkers (1991) reported that 99 percent
of fetuses with open spina bifida had one or more of these findings.
• Multiple screening strategies exist to detect Down
• syndrome during pregnancy. Which of the
following
• tests has the highest detection rate for Down
• syndrome?
• a. Maternal serum AFP
• b. Integrated screening
• c. Quadruple marker test
• d. Combined first-trimester screening
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A 38-year-old woman presents for first-trimester screening for Down syndrome at a gestational
age of 12 weeks and 1 day. The ultrasound image below was seen. What is the next step in
evaluating this finding?
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a. Offer diagnostic prenatal testing
b. Repeat the ultrasound measurement in 1 week
c. Complete the first-trimester screen and wait forher numeric risk assessment
d. Offer a sequential test as it has a high sensitivityfor Down syndrome detection
• Which of the following correctly identifies the second-trimester
analyte level abnormalities in a pregnancy at increased risk for
Down syndrome?
• a. Decreased MSAFP, increased unconjugatedestriol, increased
inhibin, increased beta hCG
• b. Decreased MSAFP, decreased unconjugatedestriol, increased
inhibin, increased beta hCG
• c. Increased MSAFP, increased unconjugated estriol,decreased
inhibin, decreased beta hCG
• d. Decreased MSAFP, decreased unconjugatedestriol, decreased
inhibin, increased beta hCG
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Two analytes used for first-trimester aneuploidy screening arehuman chorionic
gonadotropin—either intact or free β -hCG—and pregnancy-associated plasma
protein A (PAPP-A). In casesof fetal Down syndrome, the first-trimester serum free
β -hCG
level is higher, approximately 2.0 MoM, and the PAPP-Alevel is lower,
approximately 0.5 MoM
2nd trimester Pregnancies with fetal Down syndrome are character-ized by lower
aternal serum AFP levels—approximately0.7 MoM, higher hCG levels—
approximately 2.0 MoM, andlower unconjugated estriol levels—approximately 0.8
MoM(Merkatz, 1984; Wald, 1988). Levels of a fourth marker—dimeric inhibin
alph—are ele a a -vated in Down syndrome, with an average value of
1.8 MoM(Spencer, 1996). The addition of dimeric inhibin to the otherthree
markers is the quadruple or e quad test, which has a trisomy21 detection rate of
approximately 80 percent at a false-positiverate of 5 percent
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A 25-year-old primigravida from China has a Downsyndrome risk of 1:5000 based
on her first-trimesterscreening results. The finding shown is noted duringa routine
sonographic examination performed at17 weeks’ gestation. How should she be
counseledregarding this finding? a. Schedule a fetal echocardiogram at 22
weeks’gestation
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b. Offer an amniocentesis since she is nowconsidered “high-risk”
c. Inform her that this finding is seen in up to 30%
of fetuses of Asian descent
d. Inform her that her Down syndrome risk has
now increased from 1 in 5000 to 1 in 500
Second-Trimester Sonographic Markers
or “Soft Signs” Associated with Down
Syndrome Fetuses
• An echogenic intracardiac focus (EIF) is a focal
papillary mus-cle calcification that is neither a
structural nor functional car-diac abnormality. It
is usually left-sided (Fig. 14-6B). An EIFis present
in approximately 4 percent of fetuses, but it may
befound in up to 30 percent of Asian individuals
(Shipp, 2000).
• As an isolated finding, an EIF approximately
doubles the riskfor fetal Down syndrome (.
Particularly if bilat-eral, they are also common
with trisomy 13 (Nyberg, 2001)
• Which of the following fetal conditions or
events is NOT associated with the finding
of echogenic bowel during a secondtrimester sonographic examination?
• a. Down syndrome
• b. Cystic fibrosis
• c. Toxoplasmosis infection
• d. Intraamniotic hemorrhage
• Echogenic fetal bowel appears as bright as bone and is seen in
lapproximately 0.5 percent of pregnancies (Fig. 14-6D). Althoughj
• typically associated with normal outcomes, it increases the risk
• for Down syndrome approximately sixfold (see Table 14-8).
• Echogenic bowel may represent small amounts of swallowed
• blood and may be seen in the setting of AFP level elevation
• (p. 287). It has also been associated with fetal cytomegalovirus
• infection and cystic fibrosis—representing inspissated meconium
• in the latter.
• Which of the following skeletal findings during
• sonographic examination suggest an
increased fetal risk for Down syndrome?
• a. Observed:expected femur ratio ≤ .90
• b. Observed:expected humerus ratio ≤ .90
• c. Femur length:abdominal circumference
ratio < .20
• d. Observed:expected biparietal diameter
ratio < .89
• The femur and humerus are slightly shorter in
Down syn-drome fetuses, although the femur
length to abdominal cir-cumference (FL/AC)
ratio is generally within the normal rangein
the second trimester. The femur is considered
“short” forDown syndrome screening if it
measures ≤ 90 percent of thatexpected. The
expected femur length is that which correlates
with the measured biparietal diameter
(Benacerraf, 1987
• What is the appropriate screening test for
• hemoglobinopathies in patients of African
descent?
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a. Complete blood count
b. Peripheral blood smear
c. Hemoglobin electrophoresis
d. Hemoglobin S mutation analysis
• There is an increased pregnancy loss rate
following
• amniocentesis in all EXCEPT which of the
• following conditions?
• a. Twin gestation
• b. Maternal BMI ≥ 40 kg/m2
• c. Transplacental puncture with needle
• d. All of the above
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A 40-year-old infertility patient underwent an
amniocentesis at 17 weeks’ gestation. She calls
1 day later and reports that she is leaking amnionic
fluid. What should she be told about this
postamniocentesis complication?
a. Fetal survival is > 90%.
b. The risk of fetal death is 25%.
c. The risk for chorioamnionitis is 2%.
d. Fluid leakage occurs in approximately 10% of
patients.
• Early amniocentesis is defined as
amniocentesis
• that is performed during which of the
following
• gestational age windows?
• a. 9–11 weeks
• b. 11–14 weeks
• c. 12–15 weeks
• d. 14–16 weeks
• A woman undergoes a chorionic villus sampling
• (CVS) at 11 weeks’ gestation. The result shows
two
• cell lines—46,XY and 47,XY,+ 21. What is the
• appropriate next step?
• a. Repeat CVS at 13 weeks’ gestation
• b. Plan no further evaluation or treatment
• c. Offer amniocentesis for clarification of results
• d. Provide the patient with appropriate information
• regarding Down syndrome
• Chorionic villus sampling has been
associated with
• limb reduction defects under what condition?
• a. Multiple needle passes are made.
• b. Performed at a gestational age < 10
weeks
• c. Performed using a transabdominal
approach
• d. Larger volumes of chorionic villi are
sampled.
• Fetal blood sampling performed at the
placental
• insertion site is associated with which of the
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a. Shorter procedure duration
b. Increased pregnancy loss rate
c. Increased procedure success rate
d. Decreased maternal blood contamination
• Which of the following statements correctly
• describes polar body analysis when used for
• preimplantation genetic testing?
• a. It involves sampling one cell of the embryo on
• day 3.
• b. It is associated with decreased pregnancy success
• rates.
• c. It can be used to determine paternally inherited
• genetic disorders.
• d. None of the above
• Preimplantation genetic diagnosis may be
used for
• which of the following scenarios?
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a. Determine fetal gender
b. Diagnose single gene mutations
c. Human leukocyte antigen (HLA) typing
d. All of the above
• Which of the following is NOT a limitation of
• preimplantation genetic screening using fluorescence
• in situ hybridization?
• a. The result may not reflect the embryonic
• karyotype.
• b. Genomic hybridization arrays have a high failure
• rate.
• c. Mosaicism is common in cleavage-stage embryo
• blastomeres.
• d. Pregnancy rates are lower following
• preimplantation genetic screening