1M - Prenatal Diagnosis, Fetal Disorders and Fetal Therapy Flashcards
This is the science of identifying structural or functional abnormalities in developing fetus
Prenatal Diagnosis
What are the three major categories of diagnostic evaluation in prenatal diagnosis?
Fetus at high risk of genetic or congenital disorder
Fetus at unknown risk from common congenital abnormalities
Fetus ultrasonographically discovered to have structural or developmental abnormalities
Most common cause of congenital defect?
Aneuploidy
Most common etiology of birth defect which happens during development? site an example
Malformation
Deformation
Disruption
Malformation
Ex: Spina Bifida
Etiology of birth defect caused by mechanical forces which results in abnormal fetus development? Site example
Deformation
EX: Contractures caused by oligohydramnios
Etiology of birth defect which happens when genetically normal tissue is modified as the result of specific insult? Site an example
Disruption
Ex: Damage from an amniotic band causing cephalocele or limb reduction abnormality
Cluster of several abnormalities or defects? All abnormalities have the same cause. Site an example?
Syndrome
Trisomy 18
All anomalies is caused by one specific insult? Site an example?
Sequence
Oligohydramnios leading to pulmonary hypoplasia, limb contractures and facial deformities
Particular anomalies occur together frequently but do not seem to be linked etiologically? Site an example
Association
VATER - Vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia and radial dysplasia
Give two screenings for aneuploidy that every pregnant women should be offered?
Traditional or analyte based and Cell Free DNA testing
what are two maternal serum used as analytes in aneuploidy testing?
HCG and PAPP-A
used together with sonographic measurement for nuchal translucency
If tested positive for Down Syndrome during the first trimester, what will be the findings in HCG and PAPPA level?
HCG is higher and PAPPA is lower
If tested positive for Trisomy 18 and Trisomy 13, what will be the finding in HCG and PAPPA level?
Levels of both analytes are lower
What is the CRL length necessary before measuring nuchal translucency? And what measurement is associated with birth defects, increase or decrease?
38-45 and 84mm
an increase is associated with higher risk of birth defects. A measurement of 3 mm or more should receive counseling
What are the serum markers for Fetal Down Syndrome during the second trimester?
Lower maternal serum AFP, Lower unconjugated estriol, Higher HCG, higher dimeric inhibin levels
Second most common malformations?
Neural Tube defects
most common is cardiac defects
What test are given for women at risk of neural tube defects?
AFP testing and targeted US
Amniocentesis and Karyotyping is performed for confirmatory test
What is the most common risk factor for neural tube defects?
Family history
Major serum protein in embryo-fetus analogous to
albumin which is produced first by the fetal yolk and later by the liver and GI tract?
AFP
Describe the behavior of AFP in fetal serum and amniotic fluid vs maternal serum?
It steadily increases in fetal serum and amniotic fluid until 13 weeks, in which it decreases thereafter. It steadily increases in maternal serum after 12 weeks
When is AFP screening offered according to ACOG?
at second trimester at 15-20 weeks
Level of AFP in MoM to detect neural tube defect?
higher than 2.5 MoM
Level of maternal serum estriol level to detect Smith Lemli Opitz syndrome and steroid sulfatase deficiency??
higher than 0.25 MoM
This is characterized by facial malformations with mental and behavioral abnormalities associated with high estriol levels?
Smith Lemli Opitz Syndrome
This is also known as C linked ichthyosis?
Steroid sulfatase deficiency
This combines results of first and second trimester screening?
Integrated screening
When are quadruple markers done?
15-21 weeks
This screening strategy involves performing the first trimester screening and informing the patients of the results
Sequential screening
If positive, a diagnostic test is done
This screening strategy is made by identifying DNA fragments that are derived primarily from apoptotic trophoblasts, which are placental cells undergoing programmed cell death.
Cell free DNA screening
When can cell free DNA screening be made?
After 9-10 weeks
not gestational age dependent
If cell-free DNA screening is performed as a secondary screen following a positive first- or second-trimester
analyte-based test result, a normal result is not quite as reassuring. T or F?
True
What measurement of nuchal skinfold is non assuring?
More than 6 mm
tenfold risk for Down Syndrome
Echogenic intracardiac focus is usually right sided or left sided?
Left
Bilateral echogenic foci is associated with what genetic defect?
Trisomy 13 (Ptau Syndrome)
What measurement of mild pelvis renal dilatation can approximately double the risk of down syndrome?
4 mm
A bright echogenic fetal bowel increases the risk by 2 fold of what genetic defect?
Down syndrome
Couples planning to have a pregnancy with third degree couples should be advised to screen for CF? T or F
False
up to second degree relative and only those couples who are both caucasian
What mutation causes cystic fibrosis?
Mutation of CFTR gene at the long arm of chromosome 7
Classic cystic fibrosis presents as?
abnormal chloride levels in sweat chronic pulmonary disease pancreatic insufficiency liver disease obstructive asooospermia
Most common cause of familial mental retardation?
Fragile X syndrome
Fragile X syndrome is what kind of genetic defect?
X linked
only boys can acquire it
Autosomal recessive lysosomal-storage disease is characterized by absence of the hexosaminidase A
enzyme
Tay Sachs disease
Most common prenatal diagnostic procedure?
2nd trimester amniocentesis
One at 14-20 weeks
The first 1-2 ml of aspirate from amniocentesis is not used to amniocentesis but can be used for what test?
AFP testing
Needle used in amniocentesis is 20-22 gauge
Early amniocentesis is associated with procedure related pregnancy loss? true or false?
True
When do we do chorionic villus sampling?
10-13 weeks
This prenatal diagnostic procedure is used to assess for analysis of non immune hydrops?
Percutaneous umbilical cord blood sampling or fetal blood sampling or cordocentesis
What diagnostic procedure is done to check for anemia?
Fetal cerebral artery velocimetry
Arterial procedure is preferred in cordocentesis?
False because of risk of vasospasm and fetal bradycardia
This procedure allows diagnosis of few hereditary and genetic disorders prior to implantation
Preimplantation genetic diagnosis
blastomere biopsy through a hole made in zona pellucida
What are the most common causes of fetal anemia?
Red cell alloimmunization - erythroblastosis fetalis or hemolytic disease of the newborn
congenital infections - parvovirus b19
thalassemia
fetomaternal hemorrhage
What is the treatment for severe fetal anemia?
Antenatal fetal transfusion
○ Anti-D
○ Anti-Kell
○ Anti-c
○ Anti-E alloimmunization
How is alloimmunization detected?
Indirect Coombs test
What are the critical titer ranges for indirect coombs test?
1:8 to 1:32
○ If the critical titer for anti-D antibodies is 1:16
- severe hemolytic disease
■ Except for Kell sensitization
Most common alloimmunization?
Anti E alloimunization
Which alloimmunization has a greater need for fetal or neonatal transfusion?
Anti-C alloimmunization
When a d negative female is exposed to maternal d positive red cells and produces anti d antibodies that may affect the her fetus during pregnancy, what is this phenomenon called?
Grandmother effect
Most frequent minor antigen?
Kell antigen
Critical titer for kell sensitization?
1:8
Most common cause of hemolytic disease in the newborn which causes hyperbilirubinemia?
ABO blood group incompatibility
Treatment for ABO blood group incompatibilty?
Phototherapy and transfusion
ABO incompatibility is more commonly seen in pregnancies after the first one? T or F
False
it is more commonly seen during the first
Pregnancy at risk of alloimmunization but below the titer value should be assessed every when during the pregnancy?
Every 4 weeks
When being tested for fetal anemia, if the middle cerebral doppler velocity is more than 1.5 MoM the AOG is most probably?
Less than 34 - 35 weeks
Fetal blood sampling should be considered
What prenatal diagnostic procedure measures the amount of bilirubin concentration?
Amniotic fluid spectral analysis
bilirubin is usually high during mid pregnancy
middle cerebral velocimetry is more accurate
What strongly influences the management of severe fetal anemia?
Gestational age
Where should intravascular transfusion be made for fetal anemia?
Umbilical vein
for severe, early-onset hemolytic disease in
the early 2nd trimester, where should transfusion be done?
fetal peritoneal cavity
For those with fetal hydrops, where should transfusion take place?
fetal peritoneal cavity and umbilical vein
What level of hematocrit is transfusion indicated?
30%
What is the target hematocrit for non hydropic fetus?
40 - 50%
How do we compute for the volume to be transfused?
estimated fetal weight in grams by 0.02 for each 10% rise needed for the hematocrit
In severely anemic fetus at 18-24 weeks, how is does transfusion take place?
Less initially and then another one after 2 days and more every 2 to 4 weeks
MCA peak systolic velocity threshold for severe
anemia following an initial transfusion is
1.70 MoM
After transfusion, hematocrit drops by how many percent per day?
1%
and more rapid if with hydrops
To prevent anti d alloimmunization, what is the management?
Post partum administration of anti d immune globulin to at risk pregnancies within 72 hours of delivery
Anti D Ig is given at the third trimester and after delivery for rh - unsensitized women
Dose of anti d Ig given IM?
300 to 1500 IU
Qualitative test for anti d antigen?
Rosette test
If there is sufficient dose of anti d Ig given, what would be the result in indirect coombs test?
Positive
molecular weak d phenotype of d variant is treated how?
managed as d positive
no risk of alloimmunization and Ig is not needed
Those with partial D antigens are treated how?
Treated with anti D Ig due to risk of D - alloimmunization
What is the most commo presenting complaint in the presence of fetomaternal hemorrhage?
Decreased fetal movement
This fetal heart pattern warrants immediate evaluation?
sinusoidal
This is the most commonly used quantitative test for fetal red cells?
Kelihauer - Betke test or acid elution test
limitations include those with B thalassemia and those near term who have started to produce Hgb A
What is the fetoplacental blood volume at term?
125 ml/kg
A more accurate method of quantitative testing for fetal red cells than KB test is?
Flow cytometry
Most common cause of thrombocytopenia among newborns?
Alloimmune thrombocytopenia
HPA 1A - 80 - 90%
What is the platelet count of a woman whose child has alloimmune thrombocytopenia?
normal
What is the treatment for alloimmune thromobocytopenia?
IV Ig and prednisone
An autoimmune disorder in which antiplatelet IgG antibodies attack platelet glycoproteins of the fetus?
Immune thrombocytopenia or Idiopathic thrombocytopenia
This condition is caused by an excessive accumulation of serous fluid in the fetus?
Hydrops fetalis
Diagnostic findings of hydrops fetalis sonogrpahically?
more than 2 effusions (pelural, cardiac or ascites) or 1 effusion plus anasarca or whole body edema
Skin thickness of more than 5 mm
placentomegaly - 4 cm in 2nd trimester and 6 cm in 3rd trimester
hydramnios
Immune hydrops is caused by?
Red cell alloimmunization
Hgb values of less than 5g/dL
What is more common, immune hydrops or non immune hydrops?
Non immune hydrops
A form of aneuploidy which commonly cause non immune hydrops?
Turner Syndrome 45,XO
If isolated ascites is found, what may be the most probable cause of hydrops?
Parvovirus B19 or meconium peritonitis
If isolated edema is found in the upper torso or the dorsum of the hands and feet, what may be the most probable cause of hydrops?
Turner syndrome or Noonan syndrome or congenital lymphedema syndrome
This is also called Triple Edema? The fetus, mother and placenta are all edematous
Mirror Syndrome
associated with hydrops and severe preeclampsia
indicated prompt delivery
What is tachyarrhythmia foe the fetus?
more than 180 bpm
What is bradyarrhythmia for the fetus?
Less than 110 bpm
What do you call premature atrial contractions?
Ectopy
Treatment for arryhtmias?
Antiarrhythmic agents
Most common form of tachyarrhythmias?
SVT and atrial flutter
ST is characterized by an abrupt increase in fetal heart rate to
180-300 bpm with a typical range of 200-240
ST if untreated may further develop into?
reentrant tachycardia
What is the most common etiology of fetal bradyarrhyhtmia?
Congenital heart block
What treatment is given to fetus with sustained bradyarrhythmia?
maternal terbutaline
What sound does premature atrial contractions form?
Dropped beats
This is the most common fetal arrhythmia?
Premature atrial contractions
Most common etiology of androgen excess in
females with 46, X disorders of sex development
Congenital adrenal hyperplasia
What is the prenatal treatment for congenital adrenal hyerplasia?
Corticosteroid
oral dexamethasone given to the mother at a dosage of
20 mg/kg/d up to 1.5mg per day, three divided doses
What age of gestation is the critical period for genital development? and when should corticosteroid therapy start to prevent virilization?
7-12 weeks
9 weeks
Sonographically, this malformation is a well
circumscribed lung mass that may appear solid and
echogenic or may have one or multiple variably sized
cysts
Congenital cystic adenomatoid malformation
When can a Congenital cystic adenomatoid malformation lesion be considered as macrocystic?
More than 5 mm
Treatment for congenital cystic adenomatoid malformation?
dexamethasone-6.25 mg every 12
hours for four doses, or betamethasone- 12.5 mg
intramuscularly every 24 hours for two doses
What is the preferred test for fetal thyroid diseases to help guide treatment?
Fetal blood sampling
Thyroid disease if it manifests as a goiter and compresses the trachea and esophagus, can cause?
severe fetal hydramnios and neonatal airway compromise, also shoulder dystocia due to hyperextension of the neck
A pregnant woman with maternal Grave’s disease can cause what condition to the fetus?
Fetal thyrotoxicosis
A pregnant woman in medication for Grave’s disease can cause what condition to the fetus?
fetal hypothyroidisim
Discontinuation of thyroid medications is recommended during pregnancy? True or false?
True
When undergoing open fetal surgery, what procedure must the mother undergo to suppress both uterine contractions and fetal responses?
GETA
Fetal surgery is thoracic masses are usually treated with corticosteroids and surgery is only reserved for fetus with hydrops during what age of gestation?
32 weeks
Sonographically, it is a solid and/or cystic mass that arises from the anterior sacrum
Sacrococcygeal teratoma
Fetoscopic surgery is done to monochorionic diamniotic twin with stage 2 to stage 4 twin twin transfusion syndrome. What weeks of gestation is it usually done?
16-26 weeks
In congenital diaphragmatic hernia, what is the lung to head ration that confers no survival if present?
less than 0.6
Measurement of the right lung area, taken at the level
of four-chamber view of the heart, divided by the head
circumference
