Prenatal Flashcards
1
Q
What is the absolute risk of abnormal offspring (stillbirth, neonatal death, and congenital malformations) for marriages between…
consanguineous couples (first cousins)?
unrelated couples?
A
3-5% for first cousins
2-3% for unrelated couples
2
Q
Which conditions should be offered on carrier screening for individuals of ANY ethnicity?
A
Cystic Fibrosis
Spinal Muscular Atrophy
3
Q
What is the recommendation for screening for Hemoglobinopathies in all women who are currently pregnant?
A
Complete blood count with red blood cell indices-
IF this shows a low mean corpuscular volume, hemoglobin electrophoresis should be performed
4
Q
What is the recommendation for screening for Hemoglobinopathies given ethnicity?
A
CBC and hemoglobin electrophoresis in individuals of the following ethnic backgrounds... African Mediterranean Middle Eastern Southeast Asian West Indian
5
Q
What conditions does ACOG recommend carrier screening for in individuals of AJ descent?
A
Canavan disease (ASPA gene) Cystic Fibrosis (CFTR gene; note that this is recommended in all ethnicities) Familial dysautonomia (IKBKAP) Tay-Sachs (DNA + Hex A)
6
Q
What conditions does ACMG recommend carrier screening for in individuals of AJ descent?
A
Bloom Syndrome Canvan Syndrome Cystic fibrosis Familial Dysautonomia Fanconi Anemia Gaucher Disease MPS IV Niemann-Pick disease type A/B Spinal muscular atrophy Tay Sachs disease (DNA + Hex A)
7
Q
When is it recommended to offer Fragile X carrier screening?
A
When a women has a family history of intellectual disability, developmental delay, autism, or premature ovarian failure
Women with a personal history of POI or elevated follicle-stimulation hormone before age 40
Women who request it
8
Q
What percentage of babies are born with birth defects/developmental disabilities or are miscarried?
A
3-5%
(1% with heart defects)
5-10% of these children are due to human teratogens
about 20% of pregnancies miscarry
9
Q
Describe the teratogenicity of Thalidomide.
A
Thalidomide embryopathy results in severe limb reduction defects in 20-50% of exposed pregnancies
Was historically used as a sedative
Exposures occurred between 34-50 days post-LMP
10
Q
List the principles of teratology.
A
Developmental timing (MOST important factor- MUST consider what date you are using for calculating)
Dose (the greater the exposure, the greater the effect; there is typically a baseline threshold where there is no effect)
Genetic Susceptibility (of both mother and fetus metabolizing enzymes; particularly CYP)
Pattern of Malformation
Tissue Access
11
Q
Discuss the three critical periods of human development and the result of teratogens in each.
A
1-2 weeks: teratogens result in prenatal death (all or nothing period)
3-8 weeks: teratogens result in major congenital anomalies
9 weeks - birth: teratogens result in functional defects and minor congenital anomalies
EXCLUDING the brain- which is affected at any time
12
Q
Describe the teratogenicity of Warfarin.
A
nasal hypoplasia
stippled epiphyses
limb hypoplasia
Critical period: 6-9 weeks from conception (8-11 weeks from LMP)
13
Q
Describe the teratogenicity of ACE inhibitors.
A
Associated with renal tubular dysplasia (leading to oligohydramnios, Potter’s sequence, and pulmonary hypoplasia), IUGR, hypocalvaria manifested by large anterior fontanel
associated with structural defects ONLY in the 2nd and 3rd trimester (NOT in the 1st)
Reduce uterine blood flow AND block fetal ACE activity
14
Q
Describe the teratogenicity of SSRI’s.
A
First trimester- small increases in congenital heart defects, anencephaly, craniosynostosis, and omphalocele
Second/Third trimester- mild, short lived (a few days) neonatal adaptation syndrome (irritability, muscle rigidity/tremors, difficulty sleeping/feeding, temperature irregularity, heart rate disturbances, and breathing problems) that is not linked to long term adverse effects
After 20 weeks specifically- may increase risk of persistent pulmonary hypertension of the newborn
15
Q
Describe the teratogenicity of Methylmercury.
A
severe central nervous system impairment
16
Q
Describe the teratogenicity of radiation.
A
microcephaly
intellectual disability
seizures
growth restriction
minor anomalies of the eye
controversial increases in carcinogenesis
Note- most diagnostic radiologic procedures will not result in significant exposure (threshold >5 rads; >20 is most concerning)
17
Q
Describe the teratogenicity of Fluconazole.
A
Not teratogenic at normal oral dosage
IV/large oral doses (used to treat Valley fever and a few other conditions) can cause craniofacial, limb, and cardiac anomalies (concern for phenocopy of Antley-Bixler)
18
Q
Describe the teratogenicity of anticonvulsants (phenytoin, trimethadione, carbamazepine, valproate, barbituates).
A
Polydrug therapy increases risk
hypertelorism
broad depressed nasal bridge
short nose with anteverted nares
“Cupid’s bow lip”
fingernail hypoplasia (phenytoin and carbamazepine)
digital anomalies (phenytoin)
radial aplasia (valproate)
increased risk for major malformations (meningomyelocele, oral clefts, congenital heart defects, limb defects)
Developmental delay (most significantly associated with valproic acid; not seen with lamotrigine)
19
Q
Describe the teratogenicity of Accutane (isotretinoin) and other retinoids.
A
When used topically the absorption is poor and risk is low, but when taken orally- CNS anomalies ear anomalies cardiovascular defects thymus anomalies ID (30-60% of exposed fetuses)
20
Q
Describe the teratogenicity of cigarette smoking.
A
pre-pregnancy- infertility, ectopic pregnancies, and miscarriages
During- placental abruption, placenta previa, fetal growth restriction
after birth- preterm delivery, SIDS, orofacial clefts (note that clefting is variable and genetic polymorphisms in TGF-alpha appear to influence risk)
21
Q
Describe the teratogenicity of codeine.
A
unknown effects during pregnancy- HOWEVER new evidence shows risk for excessive sleepiness, feeding and respiratory difficulties in infants whose mothers are breastfeeding while taking IF the mothers are ultrarapid metabolizers of cytochrome P450 2D6 (CYP2D6)
22
Q
Describe the teratogenicity of Cytomegalovirus.
A
MOST infected newborns are asymptomatic
Some have growth restriction, cerebral calcifications, ocular abnormalities, and hepatosplenomegaly when mother has PRIMARY infection (30-40% fetal infection rate); secondary infection may also produce fetal infection but is significantly less frequent
Most common adverse outcome is hearing loss
23
Q
Describe the teratogenicity of alcohol.
A
growth restriction
central nervous system involvement (both intelligence and behavior affected)
characteristic facial features (ptosis, short palpebral fissures, smooth philtrum and thin upper vermilion)
NO known safe level of alcohol
24
Q
Describe the teratogenicity of benzodiazepines.
A
historic association of diazepam with oral clefting, however more recent studies have not shown increased risk of congenital malformations
NOTE- consistent use near term results in neonatal adaptation syndrome (similar to that seen with SSRI’s)
25
List the routine initial first trimester labs.
```
Antibody screen
Blood type/Rh (this is repeated each pregnancy)
CBC with differential
GC/Chlamidia
HIV/Hep B/C
PAP smear, UA, and culture
Rubella/RPR/Varicella Zoster
```
26
What routine obstetrical labs are offered other than the initial first trimester labs?
Genetic carrier screening (CF, hemoglobin electrophoresis, SMA)
Aneuploidy screening (maternal serum screening)
Second/Third trimester labs (GBS, Glucola)
27
What is a TORCH titer panel?
Test to look for active/historic infections during pregnancy including...
Toxoplasmosis gondii
Other (parovirus, syphilis, varicella zoster, etc.)
Rubella
Cytomegalovirus
Herpes simplex
NOTE- these are not tested for routinely (other than varicella zoster and syphilis)- only recommended if concern for primary infection
28
When should Parvovirus B19 be suspected prenatally?
US shows...
*non-immune hydrops fetalis (high output cardiac failure, aplastic anemia > myocarditis)*
Placentomegaly
Cardiomegaly
Fetal growth restriction
Rare congenital anomalies reported, generally not considered teratogenic
29
How is Parvovirus B19 managed in pregnant women?
Biweekly/weekly US after exposure to monitor for hydrops
MCA Doppler (predictor of fetal anemia if elevated)
Can consider amnio to test pregnancy
Fetal cordocentesis to assess for fetal hematorcit/reticulocyte count (if hydrops fetalis or suspected fetal anemia)
Treated with fetal packed RBC intrauterine transfusion (improves survival rate and improves symptoms- though neurological outcomes are uncertain)
30
Describe Congenital Varicella Syndrome.
US markers- hydrops, echogenic foci in liver or bowel, cardiac anomalies, limb deformities, microcephaly, fetal growth restriction
Increased risk for neonatal demise if prenatal findings are present
Postnatal Signs/Symptoms- skin scaring, limb hypoplasia, chorioretinitis, microcephaly
Greatest risk for teratogenicity due to transplacental maternal-fetal transmission is 1st or 2nd trimester
31
Describe Congenital Toxoplasmosis.
Prenatal US findings- periventricular calcifications, ventriculomegaly, hepatosplenomegaly, ascites, microcephaly, fetal growth restriction
Many asymptomatic at birth, but 90% risk for developing chorioretinitis (severe visual impairment), hearing loss, neurodevelopmental delays, rash, fever, seizures
Maternal treatment with Spiramycin (ONLY available through FDA) does not reduce or prevent fetal infection but may reduce congenital disease severity
Post-natal treatment also available
32
Describe Congenital Rubella Syndrome.
Symptoms include hearing loss (most common), vision loss/cataracts, intellectual disability, congenital heart defects, microcephaly, intrauterine growth retardation, postnatal growth retardation
33
How is Congenital Syphilis managed in pregnant women?
Benzathine penicillin G (highly effective at treating maternal disease and preventing congenital syphilis)
34
Describe Congenital Syphilis.
Can occur in any trimester
Increase risk for fetal demise/miscarriage
Presents as hepatosplenomegaly, placentomegaly, elevated peak systolic velocity in MCA, ascites, poilyhydramnios, hydrops fetalis
35
Describe Congenital Zika Virus.
Risk in any trimester
Increased risk for miscarriage/stillbirth
Symptoms include microcephaly, congenital brain abnormalities, eye abnormalities, hearing loss, seizures, joint/limb abnormalities, IUGR
36
What is hemolytic disease of the fetus/newborn (Erythroblastosis fetalis)?
when antibodies cross the placenta and lead to breakdown in fetal erythrocytes
Prenatally this can cause mild-severe anemia, hepatosplenomegaly, cardiomegaly, hydrops, and fetal demise
37
Describe the three most common blood group systems that result in isoimmunization in fetuses.
1. Rh factor/RhD antigen (can cause hemolytic disease of the fetus/newborn)
2. Lewis (mild- "Lewis lives")
3. Kell (mild to severe- "Kell kills"; note that antibodies for this do not correlate with fetal risk)
38
How is RhD alloimmunization managed?
RhD Anti-D prophylaxis (Rhogam/Rhophylac) given to mothers at 28 weeks gestation, postpartum, within 72 hours of risk of maternal-fetal interaction (i.e. CVS, amnio, vaginal bleeding)
Significantly reduces the incidence of RhD alloimmunization
Serial US evaluations with Middle cerebral artery peak systolic velocity Doppler evaluation (used to use serial CVS/amnio); starting to use NIPS (cfDNA) for Rh status (not available for other kinds blood group risks)
39
Describe the ethnicities that most/least commonly are affected with hemoglobinopathies.
Most common- African (sickle cell trait 1/10), Southeast Asian (alpha thal trait 1/20), Mediterranean (beta thal trait 1/7)
Least common- Northern European, Japanese, Native American, Inuit, Korean
NOTE- ethnic background cannot be exclusively used for risk determination
40
What prenatal evaluations should be used for Hemoglobinopathies?
```
CBC (MCV, MCH, hemoglobin level, red cell distribution width)
Hemoglobin electrophoresis (NOT hemoglobin solubility)
Carrier screening panels (though this does not always look for all variants and can miss carriers)
```
41
What findings on prenatal US should make you suspicious of Alpha Thalassemia?
Increased nuchal translucency
| Ascites, pleural effusion, hydrops (in the second trimester)
42
Describes the risk of advanced parental age.
Advanced maternal age- risk for aneuploidy increases with maternal age; structural chromosomal abnormalities (microdeletions/duplications) DO NOT
Advanced paternal age (40-45 y/o)- risk for single gene disorders (e.g. Achondroplasia, Apert Syndrome, Crouzon syndrome)
43
What is Percutaneous Umbilical Blood Sampling?
Cordocentesis
procedure done to get access to fetal blood by guiding a needle into the umbilical vein (can also be used for sample collection or transfusion)
RISKS- bleeding from puncture site, fetal bradycardia, pregnancy loss (1% depending on GA)
44
When would you conduct a PUBS procedure?
Common- diagnosis and treatment of severe anemia, Rh isoimunization, evaluation for non-immune fetal hydrops
Historical- fetal karyotyping, determining fetal blood type and platelet antigen status, diagnose single gene disorders, assessment for infection
45
What is used as a screening for open neural tube defects/abdominal wall defects during pregnancy?
Amniotic fluid Alpha-Fetoprotein (AFAFP)
Collected from amniocentesis
Automatically reflexes to detection of acetylcholinesterase and fetal hemoglobin if elevated
46
What alternative clinical indications are there for amniocentesis (other than genetic studies)?
Assess fetal lung maturity (if early delivery is considered to prevent pregnancy complications in mother; typically around 32 and 39 weeks - earlier than 32 weeks lungs will be unlikely to be fully developed)
Drain excess amniotic fluid (polyhydramnios)
47
What is confined placental mosaicism?
when mosaicism is present in the placenta but not the fetus (if mosaicism is noted on CVS, amnio f/u is needed to determine if mosaicism is present in the fetus vs confined placental mosaicism)
unlikely to be associated with defects in fetus BUT can increase risk of 3rd trimester growth restriction
can also result from trisomy rescue (fetus can be disomic BUT have UPD)
48
Which chromosomes have known clinical significance for UPD?
6, 7, 11, 14, and 15
49
What are the recommendations for prenatal diagnostic testing with invasive procedures?
Prenatal CMA recommended if >/=1 structural anomaly on ultrasound
If anatomy US is WNL, can either have karyotype OR CMA with invasive testing
If cfDNA is indicates presence of a microdeletion syndrome, confirm with CMA (because FiSH may miss smaller microdeletions)
50
What expanded findings can be detected with cfDNA screening?
Microdeletions (<7 Mb)
Rare aneuploidies (9, 16, 22)
Whole-Genome screening (CNVs of 7 Mb or greater)
Single Gene Disorders (ONLY screening -not diagnosis- and only in families with specific concerns; most useful in conditions that are sex dependent such as CAH/XLD conditions, AD conditions when mom is not affected, AR disorders with compound heterozygosity looking for paternal mutation, limited studies for trinucleotide repeats)
NOTE- none of these have been unanimously recommended in the guidelines, though most are available
51
Describe the methods for determination of maternal allele inheritance in AR/XLR conditions using cfDNA.
Relative mutation dosage (RMD)- calculates proportion of WT and mutant alleles in maternal plasma; based on allelic imbalance of slightly higher amount of one allele when fetus is homozygous; digital-PCR based (due to low amounts of cfDNA) OR NGS (but requires very deep coverage)
Relative Haplotype Dosage Analysis- combines RMD with linkage analysis by sequencing a range of het SNPs linked to the gene being tested to determine fetal haplotypes maternally vs paternally and then calculate allelic ratios in maternal plasma for the haplotype blocks; tests for these haplotypes rather than certain mutations (you can increase statistical power with larger amounts of SNPs); requires both parents and affected proband (NOT the pregnancy); really difficult when consanguinity is present
52
Describe what the first trimester US looks for.
Establish viability
Fetal Number (chorionicity/vanishing twin)
Gestational age
Structure- uterus, adnexa, cul-de-sac
Early detection of congenital anomalies
Early chromosomal aneuploidy screening
Family bonding (heart rate, first baby pictures)
LIMITATIONS- ongoing developmental fetal anatomy
Can detect an average of 50% of fetal anomalies
53
Describe what the second trimester US is used for?
Examine fetal anomalies
Fetal size
Chromosomal aneuploidy screening
Placental location
+/- Cervical length measurement (can screen for preterm delivery)
More family bonding (fetal anatomical sex, 3D US pictures)
Can detect about 60% of fetal anomalies
54
What additional US screenings are available?
```
3D/4D imaging
Biphysical profile
Color Doppler flow
Fetal ECHO
Transvaginal US
US guide for diagnostic procedures
```
55
List the most common second trimester soft markers on US.
```
Increased nuchal fold
Intracardiac echogenic focus
Renal pyelectasis
Echogenic bowel
Short humerus or femur
Choroid plexus cyst
Ventriculomegaly
Single umbilical artery/2 vessel cord
```
56
Describe the soft marker...
| Intracardiac Echogenic Focus.
Area in region of the papillary muscles of the fetal heart (not attached to the ventricular walls) that are bright as bone; left ventricle is more common than right
Occurs in ~4% of prenatal US (varies by ethnicity; more common in Asian ancestry)
Increases risk for Down Syndrome (no matter whether it is single of multiple)
NOT associated with structural cardiac abnormalities or dysfunction
57
Describe the soft marker and provide a DDx...
| Choroid Plexus Cyst
Cyst in the brain (choroid plexus)
Occurs ~1% of all first trimester US (>90% resolve by second trimester US)
Increased risk for Trisomy 18- recommend detailed fetal anatomy US to assess for other markers and aneuploidy screening (if declined recommend US to assess for IUGR)
NOT associated with increased risk for congenital brain abnormality, neurodevelopmental delays, or cerebral palsy
58
Describe the soft marker...
| Renal pyelectasis
Dilation of the renal pelvis (>/=4mm up to 32 weeks GA; >/=7mm 32 weeks and beyond)
More common in male fetuses and in the Left if unilateral
Occurs ~4.5% in pregnancy
Increases risk for Down Syndrome
30% progress to hydronephrosis (or can be stable/resolve)- follow up US at 32 weeks
Possible marker for urinary tract abnormalities (recommend renal/bladder
US at DOL 3)
59
Describe the soft marker...
| Nuchal fold
Thickening of the fetal neck area >/=6mm (up to 20.6 weeks GA)
Strongest second-trimester marker
NOT the same as the first trimester nuchal translucency
May also be a marker for Noonan Syndrome (can be a resolution of cystic hygroma)
60
Describe the soft marker and provide a DDx with follow up recommendations...
Echogenic bowel
NOTE- super hard to make/subjective; very user dependent
Fetal bowel is brighter than adjacent bone
Up to 1.5% of second trimester US
DDx is broad-
Aneuploidy (Down syndrome)
Congenital Infection (cytomegalovirus)
Cystic fibrosis
Intra-amniotic bleeding
GI tract abnormality
Requires follow-up with detailed fetal anatomy US, placenta/amniotic fluid analysis, CF carrier screening (may want more broad screening than could have been done previously), CMV screening (amniotic fluid PCR for CMV and/or maternal titers), follow-up US for IUGR (typically in 3rd trimester)
61
Describe the soft marker...
| Short long bones (humerus/femur)
Can be measured comparing actual measurement with expected measurement- shortened is typically defined as <2.5%ile for GA (femoral length tends to be shorter in African American/Asian ancestry)
Short humerus- Increased risk for Down Syndrome
Rule-out skeletal dysplasia and chromosomal abnormality
Increased risk for IUGR (f/u US in 3rd trimester)
62
Describe the soft marker...
| Single Umbilical Artery
Can result from either primary aplasia of one umbilical artery OR atrophy of one of the arteries
More commonly the Left is affected
Occurs in ~1% of pregnancies
Increased risk for chromosomal abnormalities ONLY if other anomalies are present (such as genitourinary or cardiac anomalies)- recommend detailed anatomy US and fetal ECHO
Increased risk for IUGR (f/u US in 3rd trimester)
63
Describe the soft marker...
| Mild Ventriculomegaly
Dilation of the fetal CEREBRAL ventricles
More common in male fetuses
Incidence of mild-moderate (>/=10-15mm) is ~1%
Increased likelihood for Down Syndrome (~5% with mild-moderate will have abnormal karyotype)
If isolated and not associated with a genetic anomaly and mild, neurodevelopment will be WNL >90% of the time
BUT ~7-10% of fetuses with apparently isolated mild will also have structural anomalies diagnosed after birth
64
Describe the soft marker...
| Moderate/Severe Ventriculomegaly
Dilation of the fetal CEREBRAL ventricles (moderate is typically 13-15mm; severe is typically >15mm)
Moderate- 75-93% neurodevelopment WNL (favorable outcome; unlikely to require VP shunt)
Severe- More likely to be related to obstruction and to represent hydrocephalus; most common cause is aquaductal stenosis; associated with L1CAM mutations as well as aneuploidy
Recommend fetal MRI after 22 weeks GA (though most findings will not be detectable until very late in pregnancy/after birth), detailed fetal anatomy, amnio/cfDNA with CMA and PCR for fetal infection risks (use maternal titer if not doing amnio)
Continue to monitor through pregnancy (possibly follow-up with neurology/neurosurgery)
65
List the soft markers that can be noted on US in the first trimester.
Nuchal translucency
Not considered standard of care but still detectable (and may increase risk for Down syndrome)-
Hypoplastic/absent nasal bone (can also be noted in second trimester; varies by parental ethnicity)
Tricuspid regurgitation
Abnormal ductus venosus flow
66
Describe the structural fetal anomaly...
| Congenital heart defects
Most common birth defect (combined 1-1.2% of live births; approaches 2-3% if add in bicuspid aortic valve)
Can be detected on US in first or second trimester (increased NT may indicate heart defect) or on fetal ECHO
10% risk for aneuploidy (if isolated)
67
What are common indicators for referral for fetal ECHO?
Maternal diabetes (NOT gestational diabetes though)
Maternal PKU (uncontrolled)
Maternal medications (ACE inhibitors, retinoic acid, NSAIDs in third trimester)
Infections (first trimester rubella)
Assisted reproductive therapy
First degree relative with CHD
First/second degree relative with disorder with Mendelian inheritance with CHD association
Fetal karyotype or other congenital anomaly associate with heart defects (including increased NT or single umbilical artery)
68
Describe the MOST common etiology of the following congenital heart defects...
AV canal
Coarctation of Aorta
TOF, truncus arteriosus, IAA, conventricular VSD, DORV
Ebstein's anomaly
Pulmonary valve stenosis
Supravalvular aortic stenosis
AV canal- Down syndrome
Coarctation of Aorta- Turner syndrome
TOF/truncus arteriosus/IAA/conventricular VSD/DORV- 22q11.2 deletion
Ebstein's anomaly- Lithium exposure
Pulmonary valve stenosis- Noonan syndrome
Supravalvular aortic stenosis- Williams syndrome
69
How are congenital heart defects managed when detected prenatally?
Cardiology consultation first
Prenatal management with PGE administration and counseling for the risk of preterm delivery
Postnatal management- ECMO/surgery may be needed; counseling for risk for postnatal morbidity/mortality as well as neurocognitive and developmental outcomes
Recurrence risk of 1-4% for offspring or sibling (if isolated)
70
Describe the structural fetal anomaly...
| Open Neural Tube Defect
Group of congenital anomalies that affects the developing central nervous system and vertebral column
Typically develops 3-4 weeks post-fertilization (which is why it is important to start maternal folate supplementation early/before pregnancy and increased folic acid dosage if there are other risk factors)
Location of defect determines the congenital anomaly
Amnio is most important because it can cover most of the conditions on the DDx (because you can use AFAFP)
71
Describe the structural fetal anomaly...
| Anencephaly
Failure of closure of anterior neural tube
1/1000 pregnancies in US
Counseling considerations-
Can have prolonged gestational age
Palliative care for patients who elect to continue the pregnancy (with IUFD, stillbirth, and neonatal demise being common)
Donation of the organs
72
Describe the structural fetal anomaly...
| Myelomeningocele
Most common ONT defect (also called spina bifida)
1-2/1000 live births in the US
Protrusion of neural elements and meninges through open vertebral arches (failure of vertebral arches to close prior to 6th week)
Determine size and level of defect to be able to counsel best (the larger/higher the defect, the greater the risk for morbidity/mortality; most common in the lumbosacral level)
Counsel about degree of independent ambulation, bowel/bladder function, sexual function, ID (~10% risk)
73
Describe the structural fetal anomaly...
| Encephalocele
Skin-covered neural tube defect affecting the cranium (either *occipital*, frontal, or parietal)
1/2000 live births
Determine size/location/content for accurate prognosis (size not as important, but content is most important)
Microcephaly is likely if brain tissue is present (increased risk for ID/DD)
74
What signs on US may be present that could indicate increased risk for ONT defects?
Cranial changes...
Lemon sign- head bilaterally flattened in frontal region
Banana sign- cerebellum is rounded and width is decreased
Arnold-Chiari malformations
Fetal legs...
Clubfoot
75
What are the options for treatment of Myelomeningocele noted on prenatal US?
```
Traditional postnatal repair (closure, VP shunt placement)
Prenatal repair (reduces trauma to myelomeningocele, decrease leakage of CSF, and decreases exposure to amniotic fluid BUT increases pregnancy complications)
```
76
List the DDx for ONT Defects.
Sporadic
Teratogens (anticonvulsants, pre-gestational DM, exposure to hot tubs/saunas/hyperthermia)
Amniotic band sequence, VACTRL sequence
Chromosomal changes (anencephaly/myelomeningocele associate with Trisomy 18; encephalocele associated with Trisomy 13)
Singe gene disorders (Meckel-Gruber syndrome, Walker-Warburg syndrome, Joubert syndrome)
77
Describe the fetal structural anomaly and recommendations for follow up after seeing it...
Agenesis of the Corpus Callosum
Failure of axons to cross the midline between right and left hemispheres of the brain (complete or partial absence)
If this is isolated, it can be asymptomatic OR can result in ID/DD of any severity and/or epilepsy
Associated with congenital brain abnormalities (Dandy-Walker malformation, hydrocephalus, microcephaly, pachygyria, lissencephaly) that are GA dependent
Fetal MRI may be needed to confirm; consider amnio, TORCH titer, and/or molecular testing
Postnatal imaging/neurology important (even if isolated)
78
Describe the fetal structural anomaly...
| Holoprosencephaly
Most common forebrain abnormality
Failed/incomplete prosencephalon separation (can be Alobar, Semilobar, or Lobar)
Seen with craniofacial anomalies 80% of the time
EXTREMELY variable phenotypic expression- must evaluate parents for microforms (single central incisor, hypotelorism, anosmia, absent labial frenulum) before assuming simplex case
Increased risk of morbidity/mortality (especially in severe cases)
79
What is the DDx for holoprosencephaly?
High likelihood of underlying chromosomal abnormality (25-50%; Trisomy 13/18, triploidy, 13q-, 18p-)
Other syndromic causes (25%; Smith-Lemli Opitz, Meckel syndrome, Kallman syndrome)
Non-syndromic (AD) causes
Teratogens (alcohol, phenytoin, diabetes, infection)
80
Describe the fetal structural anomaly...
| Duodenal Atresia
Congenital absence of closure of portion of the duodenal lumen (complete or partial blockage of the duodenum; most common neonatal intestinal obstruction)
"Double bubble" sign when dilation is in proximal duodenum and stomach
81
What is the DDx for Duodenal Atresia?
Down Syndrome (20-40%)
Sporadic, multifactorial
RARELY other syndromes OR familial AD
82
Describe the fetal structural anomaly...
| Gastroschesis
Evisceration of small +/- large bowel through the abdominal wall (important to note where it occurs- this can determine gastroschesis vs oomphalocele)
Counseling for risk of intestinal atresia and bowel dilation/IUGR/PTL/IUFD
Can be repaired postnatally
83
What is the DDx for Gastroschesis?
Typically isolated, sporadic, or multifactorial
| UNLESS it is a ruptured omphalocele, then see that DDx
84
Describe the fetal structural anomaly...
| Oomphalocele
Abdominal wall defect with sac of amnion containing herniated abdominal viscera (can include or exclude the liver)
2/3 have other congenital anomalies (specifically need to look for cardiac anomalies; if also contains the liver there is a risk for lung hypoplasia)
85
What is the DDx for oomphalocele?
Chromosomal abnormalities- trisomy 13 and 18 (10-30%)
| Beckwith-Wiedmann syndrome (10-20%)
86
Describe the fetal skeletal anomaly...
| Clubfoot (Talipes Equinovarus)
Abnormal relation of the foot/ankle to the tibia and fibula; foot excessively plantar flexed with forefoot bend medially and sole facing inward
1-4/1000 pregnancies
More commonly in males and more commonly bilateral
Refer to pediatric orthopedics for postnatal repair/casting
87
What is the DDx for fetal Clubfoot (Talipes Equinovarus)?
Isolated (requires detailed anatomy US because there is a 10-14% risk for other structural anomalies)
Chromosomal abnormalities (trisomy 18)
Neural tube defects or spine abnormalities
Musculoskeletal disorders
Arthrogryposis
Hereditary (possibly AD)
88
Describe the fetal skeletal anomaly...
| Polydactyly
Extra digit may be well developed and contain bone or may be rudimentary with soft tissue
Preaxial (radial or tibial) vs postaxial (ulnar or fibular)
More common in African American/Black ancestry
89
What are the DDx for fetal polydactyly?
Isolated
Familial (AD)
Chromosomal Abnormality (typically not found when isolated)
Other genetic syndromes (typically not found when isolated)
90
Describe the fetal skeletal anomaly...
| Skeletal dysplasia
Genetically heterogenous group of >450 distinct disorders
DDx is challenging because these are rare, most US findings are not pathognomic for a specific disorder (US approximately 40-50% accurate in diagnosing type), so this is just for narrowing down DDx and understanding lethal vs non-lethal likely
Normal testing options available and can use fetal CT to help further diagnose (BUT note there is a radiation exposure risk)
91
What prenatal US measurements/markers are suggestive of higher lethality risk in skeletal dysplasias?
Chest to abdominal circumference ration <0.6
Femur length to abdominal circumference ratio <0.16
Long bone measurements <3rd %ile
Increased risk with other congenital anomalies, polyhydramnios, hydrops fetalis
Double dominant (homozygous or compound heterozygous fetus)
92
What prenatal US measurements/markers are suggestive of higher morbidity/mortality in renal anomalies?
Presence of oligohydramnios +/- bilateral renal involvement (due to risk for pulmonary hypoplasia/renal disease and failure)
93
Describe the fetal anomaly...
| Lower Urinary Tract Obstructions
Fetal bladder outlet obstructions
Most commonly posterior urethral valves in males (60%) and urethral atresia in females (40%)
First trimester megacystitis may spontaneously resolve and may not be LUTO
Increased morbidity and mortality is dependent on degree/timing/etiology of obstruction, presence of oligohydramnios/anhydramnios or pulmonary hypoplasia
Options for management in pregnancy (IF renal function is determined to be present per fetal bladder aspiration) include vesicoamniotic shunting/fetoscopic ablation
94
What is the DDx for Lower Urinary Tract Obstructions (LUTOs)?
Chromosomal aneuploidy
CNVs
Familial
95
Describe the fetal anomaly...
| Tracheoesophageal Fistula
>/= 1 abnormal connections between trachea and esophagus
CANNNOT be seen on US- only suspected with polyhydramnios, absent stomach bubble (typically in the 2nd or sometimes not until the 3rd trimester)
Repair postnatally with good outcomes (however there is increased risk for GER, dysphagia, restrictive airway disease)
96
What is the DDx for Tracheoesophageal fistula?
```
Sporadic/isolated
VACTERL
Teratogen (maternal diabetes)
Chromosomal (trisomy 18, 21)
CNVs (22q11.2 deletion)
Single gene disorders
```
97
Describe the fetal anomaly...
| Diaphragmatic hernia
Incomplete formation of the diaphragm with abdominal viscera herniating into the chest cavity
Results in increased risk for pulmonary hypoplasia and pulmonary hypertension
More common in Left (85-90%) and isolated
Options for postnatal repair (stabilize with ECMO and close the defect) OR fetal repair (fetal endoscopic tracheal occlusion) which can improve lung growth in utero and increase maturity
98
What are US measurements/markers that modulate prognosis for diaphragmatic hernia noted prenatally?
General mortality (survival) is ~70-75%
Whether the liver is included in the herniation
Lung to head ratio is <0.6
99
What is the DDx for prenatally noted diaphragmatic hernia?
Chromosomal (trisomy 18 adn 21, Pallister-Killian syndrome)
CNVs
Familial AR, AD, or XL syndromes
Syndromic (Beckwith Wiedmann syndrome, CDLS, Fryns syndrome)
100
Describe the fetal anomaly...
| Cystic Adenomatoid Malformation of the Lung
Benign hamartomatous or dysplastic lung tumor (Macrocystic, Mixed, or Microcystic)
NOT chromosomal- always sporadic
Can regress prenatally or can be resected postnatal
Risk for fetal hydrops and maternal MIRROR
101
Describe the fetal anomaly...
| Cystic hygroma
multiseptated cysts of lymphatic system (vascular malformation in delayed development/absent communication between jugular lymph sacs and internal jugular veins)
Most commonly seen as nuchal (which has a rare risk for airway obstruction); must evaluate to see if this is just a continuum of the nuchal (which is important because prognosis is different)
About 25% resolve spontaneously with some progressing to hydrops fetalis with complete lymphatic obstruction (IUFD)
Commonly seen with other anomalies (especially cardiac)
Most can be seen by 10 weeks GA
102
What is the DDx for a cystic hygroma?
Chromosomal (50-60% risk; trisomy 21, 13, 18, *Turner syndrome*, triploidy)
CNV (22q11.2 deletion and others)
Other genetic disorders (Noonan syndrome, multiple pterygium syndrome, Robert's syndrome)
103
Describe the fetal anomaly...
| Facial clefting
Most common fetal craniofacial malformation
Cleft lip +/- palate is distinct from cleft palate
CL+/- CP is 1/1000 births and more commonly in males
Cleft palate is 5/1000 births and more commonly in females
Team to address feeding difficulties, dental, plastic surgery (typically not immediate), speech therapy, plus others as clinically indicated
3D US may aid in detection of cleft palate (which is hard to see on traditional US)
104
What is the DDx for facial clefting?
Isolated- multifactorial, AD/AR/XL, teratogenic
Other congenital anomalies (chromosomal, .300 syndromic causes)
Midline may indicate a congenital brain malformation and could be associated with holoprosencephaly of trisomy 13
105
Provide a DDx for elevated maternal serum screening AFP in the second trimester.
elevated (>2.5 MOM) serum AFP on second trimester screening can be related to open neural tube defects OR underestimated gestational age (most common), ventral wall defects, unrecognized twin gestation fetal demise, abnormality in the fetal kidney
ALWAYS order when screening with cfDNA
106
What is used to calculate risk for the first trimester screening (both US findings and serum analytes)?
Ultrasound Eval (11-14 weeks GA)-
crown rump length (to get more accurate measurement of GA)
nuchal translucency- greater than 2.5-3.0mm (depending on GA) is called increased
nasal bone presence/absence (only some locations)
Analyte Eval-
pregnancy associated plasma protein A (PAPP-A; produced by the placenta)
human chorionic gonadotrophin (hCG; produced by the placenta)
107
What is the pattern of measurements on first and trimester screen that indicates increased risk for Down Syndrome?
```
First-
Increased NT
Decreased PAPP-A
Increased b-hCG
Second-
Decreased AFP
Decreased uE3
Increased hCG
Increased Inhibin A
```
108
What is the pattern of measurements on first and second trimester screen that indicates increased risk for Trisomy 18?
```
First-
Increased NT
Decreased PAPP-A
Decreased b-hCG
Second-
Decreased AFP
Decreased uE3
Decreased hCG
```
109
What is the pattern of measurements on first and second trimester screen that indicates increased risk for Trisomy 13?
```
First-
Increased NT
Decreased PAPP-A
Decreased b-HCG
Second-
Decreased AFP
Decreased uE3
Decreased hCG
```
110
What is the DDx for absence of nasal bone?
Aneuploidies (T13, 18, 21, and Turner syndrome)
| Afro-Caribbean ancestry (~10% presence in normal fetuses)
111
What is used to calculate risk for the second trimester screening?
Triple Screen- AFP, human chorionic gonadotropin (hCG), unconjugated estriol (uE3)
Quad Screen (15-21 weeks 6 days)- AFP, hCG, uE3, dimeric Inhibin A (DIA)
Penta screen- AFP, hCG, uE3, DIA, Hyperglycosylated hCG
*Note that AFP, uE3, and Inhibin A are all produced by the fetus
112
What information is necessary for accurate interpretation of maternal serum screening?
```
Maternal age (for baseline risk)
Gestational age of fetus (for accurate timing of normal values since the analytes vary over time)
Maternal diabetes (diabetic women have lower AFP but higher levels of ONTD)
Mother's ethnicity (African-American women have higher levels of AFP but lower levels of ONTD)
Maternal weight (maternal serum markers are adjusted depending on maternal weight)
Singleton vs multiple gestation (values will change based on number of babies)
Smoking (leads to increased screen positive rates, especially for T18 when using combined or integrated tests; higher Down syndrome screen positive rates for quad test, but not first trimester or combined/integrated)
```
113
Describe the combined first/second trimester screening options.
Integrated (highest DR of combined tests; also screens for ONTDs)- First trimester screening (serum analytes and US findings) + Quad screening are both done before results are reported
Sequential Stepwise- First trimester screening results reported and then Quad screening is performed and final results are given to family
Contingent- First trimester screening positive you do diagnostic testing; if negative no further testing is done; if intermediate second trimester screening is offered
114
What conditions other than aneuploidy can maternal serum screening detect?
Elevated AFP- abdominal wall defects (omphalocele and gastroschisis)
Decreased uE3- Smith Lemli Opitz Syndrome; Steroid sulfatase deficiencies
Extremely elevated AFP- Congenital nephrotic syndrome
Low PAPP-A (below 5th percentile)- obstetrical complications
115
What are the carrier frequencies for the four most common AJ conditions?
Gaucher- 1/14
Cystic Fibrosis- 1/24
Tay Sachs- 1/30
Familial Dysautonomia- 1/35
116
What is the genotype of an ovarian teratoma?
maternal UPD of all chromosomes
117
What is the genotype of a full hydatidiform mole?
paternal UPD of all chromosomes
118
What is the genotype of a partial mole?
triploidy (digyny- 69, XXX or diandry- 69 XXY)
119
```
What is the Cystic Fibrosis carrier frequency for the following ethnic backgrounds:
AJ
Caucasian
Hispanic
African American
Asian
```
```
AJ- 1 in 24
Caucasian- 1 in 25
Hispanic- 1 in 46
African American- 1 in 65
Asian- 1 in 94
```
120
```
What is the SMA carrier frequency for the following ethnic backgrounds:
AJ
Caucasian
Hispanic
African American
Asian
```
```
AJ- 1:41
Caucasian- 1:35
Hispanic- 1:117
African American- 1:66
Asian- 1:53
```
121
```
What is the Tay Sachs carrier frequency for the following ethnic backgrounds:
AJ
French Canadian
Cajun
General Population
```
AJ- 1 in 30
French Canadian- 1 in 50
Cajun- 1 in 50
General Population- 1 in 300
122
What pattern on quad screen indicates that true gestational age may be beyond provided dates?
Increased AFP
Increased uE3
Slightly increased Inhibin A
Decreased hCG
