Prenatal Flashcards
What is the absolute risk of abnormal offspring (stillbirth, neonatal death, and congenital malformations) for marriages between…
consanguineous couples (first cousins)?
unrelated couples?
3-5% for first cousins
2-3% for unrelated couples
Which conditions should be offered on carrier screening for individuals of ANY ethnicity?
Cystic Fibrosis
Spinal Muscular Atrophy
What is the recommendation for screening for Hemoglobinopathies in all women who are currently pregnant?
Complete blood count with red blood cell indices-
IF this shows a low mean corpuscular volume, hemoglobin electrophoresis should be performed
What is the recommendation for screening for Hemoglobinopathies given ethnicity?
CBC and hemoglobin electrophoresis in individuals of the following ethnic backgrounds... African Mediterranean Middle Eastern Southeast Asian West Indian
What conditions does ACOG recommend carrier screening for in individuals of AJ descent?
Canavan disease (ASPA gene) Cystic Fibrosis (CFTR gene; note that this is recommended in all ethnicities) Familial dysautonomia (IKBKAP) Tay-Sachs (DNA + Hex A)
What conditions does ACMG recommend carrier screening for in individuals of AJ descent?
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)
When is it recommended to offer Fragile X carrier screening?
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
What percentage of babies are born with birth defects/developmental disabilities or are miscarried?
3-5%
(1% with heart defects)
5-10% of these children are due to human teratogens
about 20% of pregnancies miscarry
Describe the teratogenicity of Thalidomide.
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
List the principles of teratology.
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
Discuss the three critical periods of human development and the result of teratogens in each.
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
Describe the teratogenicity of Warfarin.
nasal hypoplasia
stippled epiphyses
limb hypoplasia
Critical period: 6-9 weeks from conception (8-11 weeks from LMP)
Describe the teratogenicity of ACE inhibitors.
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
Describe the teratogenicity of SSRI’s.
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
Describe the teratogenicity of Methylmercury.
severe central nervous system impairment
Describe the teratogenicity of radiation.
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)
Describe the teratogenicity of Fluconazole.
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)
Describe the teratogenicity of anticonvulsants (phenytoin, trimethadione, carbamazepine, valproate, barbituates).
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)
Describe the teratogenicity of Accutane (isotretinoin) and other retinoids.
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)
Describe the teratogenicity of cigarette smoking.
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)
Describe the teratogenicity of codeine.
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)
Describe the teratogenicity of Cytomegalovirus.
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
Describe the teratogenicity of alcohol.
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
Describe the teratogenicity of benzodiazepines.
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)
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
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)
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
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
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)
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
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
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
How is Congenital Syphilis managed in pregnant women?
Benzathine penicillin G (highly effective at treating maternal disease and preventing congenital syphilis)
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
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
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
Describe the three most common blood group systems that result in isoimmunization in fetuses.
- Rh factor/RhD antigen (can cause hemolytic disease of the fetus/newborn)
- Lewis (mild- “Lewis lives”)
- Kell (mild to severe- “Kell kills”; note that antibodies for this do not correlate with fetal risk)
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)
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
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)
What findings on prenatal US should make you suspicious of Alpha Thalassemia?
Increased nuchal translucency
Ascites, pleural effusion, hydrops (in the second trimester)
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)
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)
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
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
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)
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)
Which chromosomes have known clinical significance for UPD?
6, 7, 11, 14, and 15
