Prenatal Screening, Diagnosis and Treatment Flashcards
define screening
allows high risk individuals to be selected out of a low risk population at risk for a given diagnosis or complication
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
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)
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
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
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
who should be screened for sickle cell anemia
more common among african americans–all should be screened in pregnancy
what is the heterozygote advantage of sickle cell trait
heterozygotes confer resistance to plasmodium vivax (malaria)
how do you screen for sickle cell anemia
hemoglobin electrophoresis which distinguishes HbS from HbA
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
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
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
in what populations is beta-thalassemia more common
mediterranean, asian, african
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
how do you screen for alpha and beta thalamssemia
CBC
what is the only way to achieve a definitive diagnosis of aneuploidy
karyotype
what are the components of first trimester screening for aneuploidy
nuchal translucency combined with pregnancy-associated plasma protein A (PAPP-A) and beta hCG
what are the components of the second semester screen for aneuploidy
quad screen–> MSAFP estriol, beta hCG and inhibin
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
what is the most common cause of down syndrome
trisomy 21
describe the typical Down syndrome phenotype
short stature
classic facies
developmental delay
mental retardation with IQs ranging from 40 to as high as 90
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
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
what is the sensitivity for first trimester screening for down syndrome
82-87%
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
no
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
- decreased
- decreased
- elevated
- 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
