Prenatal Screening, Diagnosis and Treatment Flashcards by Alana Meikle

define screening

allows high risk individuals to be selected out of a low risk population at risk for a given diagnosis or complication

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how does prenatal diagnosis differ from prenatal screening

prenatal diagnosis is nearly always diagnostic and is usually far more specific than screening but amniocentesis and CVS (which are used for prenatal diagnosis) have greater risk of complications, including pregnancy loss

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what is the genetic abnormality behind cystic fibrosis

autosomal recessive

results from abnormality in cystic fibrosis transmembrane conductance regulator (CFTR) which is the gene responsible for chloride channels

almost call CF patients have chronic lung disease because of recurrent infections leading to irreversible lung damage and strain on the right ventricle (cor pulmonale)

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clinical manifestations of CF

almost call CF patients have chronic lung disease because of recurrent infections leading to irreversible lung damage and strain on the right ventricle (cor pulmonale)

85% of CF patients have pancreatic insufficiency manifested by chronic malabsorption and failure to thrive

life limiting: lung disease

median survival is close to 40 years for those more today in the USA

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what is the genetic abnormality behind sickle cell anemia

autosomal recessive

single point mutation in gene for beta chain og HgB

resulting HbS forms polymers that when deoxygenated cause the cells to lose biconcave shape and become sickled

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clinical picture of sickle cell anemia

hemolytic anemia due to sickled shape

shortened life expectant

frequent pain crises secondary to vaso-occlusion of small vessels by the dysmorphic erythrocytes

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who should be screened for sickle cell anemia

more common among african americans–all should be screened in pregnancy

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what is the heterozygote advantage of sickle cell trait

heterozygotes confer resistance to plasmodium vivax (malaria)

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how do you screen for sickle cell anemia

hemoglobin electrophoresis which distinguishes HbS from HbA

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genetic abnormality behind tay-sachs disease

autosomal recessive

most common in Eastern European Jews and french canadians

1/27-30 Ashkenazi Jews is a carrier for abnormal tay-sachs allele (so the incidence in this pop is 100x higher) –> possibly due to a founder effect

occurs due to deficiency of hex A which is responsible for degradation of GM2 gangliosides–> accumulation of gangliosides–> enlarged neurons–> cellular dysfunction–> neuronal death

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clinical manifestation of tay-sachs

infants develop symptoms approx 3-10 months after birth

early sx–> loss of alertness, excessive reaction to noise (hyperacusis)

progressive developmental delay and neurologic degeneration in intellectual and neurologic function

myoclonic and akinetic seizures can present 1-3 months later

cherry red spot is seen on fundoscopic eye exam

eventually suffer from paralysis, blindness and dementia and typically die by age 4

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what are the thalassemias

set of hereditary hemolytic anemias caused by mutations that result in the reduction in the synthesis of either alpha or beta chains

results in imbalance of globin chain synthesis and subsequently unpaired globin chains produce insoluble tetramers that precipitate in the cell and cause damage to membranes

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in what populations is beta-thalassemia more common

mediterranean, asian, african

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what does the most severe form (4 mutations) of alpha thalassemia cause

fetal hydrops

is incompatible with life

infants are delivered premature and are pale, hydropic, severely anemic and have splenomegaly

fetal hemoglobin electrophoresis reveals no HbF, no HbA and approximately 90-100% Hb Bart

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how do you screen for alpha and beta thalamssemia

CBC

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what is the only way to achieve a definitive diagnosis of aneuploidy

karyotype

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what are the components of first trimester screening for aneuploidy

nuchal translucency combined with pregnancy-associated plasma protein A (PAPP-A) and beta hCG

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what are the components of the second semester screen for aneuploidy

quad screen–> MSAFP estriol, beta hCG and inhibin

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what does NIPT look at

looks for aneuploidy in cell free fetal DNA in maternal serum

not applicable in twins
can miss chromosomal mosaicism
do not currently assess all chromosomes as a karyotype does

BUT are highly sensitive and specific in women with high risk of aneuploidy

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what is the most common cause of down syndrome

trisomy 21

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describe the typical Down syndrome phenotype

short stature
classic facies
developmental delay
mental retardation with IQs ranging from 40 to as high as 90

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what are the associated physical anomalies associated with Down syndrome

cardiac defects

duodenal atresia or stenosis

short limbs

*some of these can be seen by U/S but up to 40-50% of fetuses with Down syndrome will not have diagnosable anomalies by U/S, making U/S a poor screening tool

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how do women undergo screening for Down syndrome

first trimester screen (nuchal translucency with PAPP-A and bhCG) and/or the quad screen (MSAFP, nCG, estriol and inhibin A) between 15-20 weeks gestation

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what is the sensitivity for first trimester screening for down syndrome

82-87%

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what is the sensitivity for quad screening for down syndrome

80% (alone)

what is the sensitivity of the combo of first trimester and quad screening for down syndrome

95% (with screen positive rate of 5%)

how sensitive is NIPT to detect down syndrome

98-99% or better

what are the common trisomies

13, 18, 21

what is another name for trisomy 18

Edward syndrome

what is the sensitivity of dual first trimester and quad screening for trisomy 18

90%

what is the sensitivity of NIPT for trisomy 18

97%

what is the effect of trisomy 18

lethal aneuploidy nearly all neonates die in the first two years of life associated with multiple congenital abnormalities which are typically seen on U/S (in 95% of cases)

is U/S a reasonably screening tool for trisomy 18

yes--95%

what are the physical signs suggestive of Edward syndrome

clenched fists overlapping digits rocker bottom feet cardiac defects (VSD, tetralogy of fallot) omphalocele congenital diaphragmatic hernia neural tube defects choroid plexus cysts

what is another name for trisomy 13

patau syndrome

what is the ultimate effect of trisomy 13

lethal aneuploidy 85% will not live past 1 year

what are the common abnormalities associated with trisomy 13

holoprosencephaly cleft lip and palate cystic hygroma single nostril or absent nose omphalocele cardiac anomalies (hypoplastic left heart) limb anomalies (clubfoot and clubhand, polydactyly, overlapping fingers)

are the first trimester and quad screens good tools for trisomy 13 screening

no--outcomes are variable however, anomalies are often visible on U/S

define turner's syndrome

45X karyotype

define klinefelter syndrome

47, XXY karyotype

describe the phenotype of turner's syndrome

phenotypically female short stature primary amenorrhea sexual infantilism webbed neck low set ears low posterior hairline epicanthal folds wide carrying angle of arms shield-like chest wide set nipples short fourth metacarpal renal anomalies lymphedema of extremities at birth CV anomalies-->coarctation of the aorta

what anomaly is seen on U/S in Turner's

cystic hygroma

is there a screening test for turners

no --might be available to diagnose through NIPT

is there a screening test for Klinefelters

common findings in klinefelters

small, firm testes with hyalinization of the seminiferous tubules infertility gynecomastia mental retardation elevated gonadotropin levels due to decreased levels or circulating androgens

how many cells is a morula and when does this form

16 cells day 4

what developmental form implants into the uterus

blastocyst

when does gastrulation occur

week 3

what is the period of organigenesis

week 3-8 after conception--5-10 GA

when does the neural tube form

begins day 22-23 after conception (week 4) anterior neuropore (brain) closes by day 25 posterior neuropore (spinal cord) closes by day 27 closure of the neural tube coincides with formation of its vascular supply majority of NTDs develop as a result of defective closure by week 4 of development (6 weeks GA)

why do women take folic acid

to prevent NTDs

what is the classic U/S finding in spina bifida

"lemon" sign--> concave frontal bones "banana" sign--> cerebellum that is pulled caudally and flattened ventriculomegaly and club feet are also seen

what blood test screens for NTDs

MSAFP an open neural tube leads to elevated amniotic fluid alpha-fetoprotein (AFP) that crosses into the maternal serum

when does heart formation start

week 3 after conception

describe Eisenmenger physiology

right ventricular hypertrophy pulmonary HTN right to left shunt

what is tetralogy of fallot

VSD with an overriding aorta, pulmonary stenosis or atresia, RV hypertrophy

what is Potter syndrome

renal failure leading to anhydramnios, which in turn causes pulmonary hypoplasia and contractures or deformations of the limbs in the fetus it is a bilateral renal agenesis

what does sensitivity of a test represent

the number of people are affected and test positive

what does specificity of a test represent

the number of people who are unaffected and test negative

what is the nuchal translucency test and what does it look for

good for aneuploidy--down syndrome in particular measures the posterior feal neck taken in profile view

``` how are 1. beta hCG 2. estriol 3. MSAFP 4. inhibin affected in trisomy 21 ```

1. decreased 2. decreased 3. elevated 4. elevated

``` how are 1. beta hCG 2. estriol 3. MSAFP 4. inhibin affected in trisomy 18 ```

all decreased

``` how are 1. beta hCG 2. estriol 3. MSAFP 4. inhibin affected in trisomy 13 ```

depends on defects

what does MSAFP screen for

NTDs is higher in NTDs, lower in down syndrome

what are other causes for elevated MSAFP (not NTDs)

inaccurate dating (increases with gestational age) abdominal wall defects multiple gestations placental abnormalities fetal demise

what should you be aware of in a patient with elevated MSAFP without elevated amniotic AFP

greater risk o pregnancy complications associated with the placenta (abruption, preeclampsia, IUGR, IUFD)

what might an echogenic intracardiac focus (EIF) suggest on U/S

down syndrome is a calcification of the papillary muscle without an particular pathophysiology not a very helpful test tho

when can you get samples for NIPT

by 10 weeks

when can you perform amniocentesis

after 15 weeks early amniocentesis has higher risks for pregnancy loss

how do you do amniocentesis

place a needle transabdominally through the uterus into the amniotic sac and withdraw some of the fluid fluid contains sloughed fetal cells that can be cultured and karyotyped cultures take 5-7 days to grow FISH can be done to ID genetic problems

common risks of amiocentesis

rupture of membranes preterm labour fetal injury (rare)

what is CVS

chorionic villus sampling can be used to obtain karyotype sooner than amniocentesis because performed at 9-12 weeks place a catheter into intrauterine cavity, either transabdominally or transvaginally, and aspirate small quantity of chorionic villi from placenta

what is the risk of complications from CVS

higher than amniocentesis can be confused in cases of placental mosaicism preterm labour premature ROM previable delivery fetal injury

why dont we do CVS before 9 weeks

assoc with limb injury secondary to vascular interruption

Prenatal Screening, Diagnosis and Treatment Flashcards

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