Prenatal Growth Defects and Dx Flashcards
When is a baby considered pre-term?
Born before 34 weeks (38 normal pregnancy)
When are the organ systems of the fetus well-established?
By the second month of gestation
When does the embryo gain the most length and weight?
Length: 3-6 months gestation
Weight: 7-9 months gestation
Low birth weight
Less than 5 lbs. 8 oz.
SGA and IUGR
Small for gestational age (SGA)
Intrauterine growth restriction (IUGR)
At or below 10th %
Toxic insult/hereditary - one of most common causes is multiple births
Barker’s hypothesis
Obesity
Hypertension
Hypercholesterolemia
Type 2 Diabetes
Cardiovascular Disease
(IUGR) - produces problems as adults
Twins
7-11/1000 dizogotic
3-4/1000 monozygotic
Only 29% of women pregnant with twins give birth
10-20% die at birth
12% of premature infants are twins
ARTs = 1-2% of all pregnancies = more multiple birth pregnancies
Dizygotic twinning
Two separate embryos, typically separate placentas (sometimes they fuse)
Twin transfusion syndrome
One embryo receives too much blood supply the other too little
Defects of the primitive streak
Can produce conjoined twins
When is the appearance and dissapearance of the herniated gut loop common?
Appearance: wk 6
Dissapearance (reduces): wk 10
At what point in gestation is a fetus viable outside of the womb?
7 months (when lungs begin to make surfactant)
Types of birth defects
Malformations: Most occur during the 3rd-8th weeks, but the 1st 2 weeks are important too!
Disruptions: Alterations in already formed structures(vascular accidents, amniotic bands)
Deformations: Mechanical forces alter a structure (Potter’s face - renal agenesis)
Abnormal gene signaling (classification of abnormal fetal development)
Malformation
Vascular accidents are classified as what type of malformation during fetal development?
Disruption
Amniotic bands
The amnion strands wraps around and constricts blood floow (extrimities)
AER disruption can also produce similar effects
Causes of birth defects
Microarrays
Specific DNA sequences hybridized to patient’s DNA or RNA. Detects mutations and changes in expression.
Exome sequencing
Sequencing coding regions (exons) of a patient’s DNA where most genetic variants occur and which represent only about 1% of a patient’s total DNA.
Increased incidence of trisomy 21 with increasing maternal age:
Age 25 = 1/2000
35 = 1/300
40 = 1/100
Turner syndrome
45 X monosomy
Angelman Syndrome
15q11-15q13: maternal deletion (imprinting)
Thalidomide
Characteristic limb defects (absence of the long bones)
Zika virus
Can cause necrosis of brain tissue (microcephaly)
Environmental causes of defects
Alcohol
Retinoids (acutane)
Thalidomide
Antieplileptic drugs (dilantin, valproic acid)
Radiation
Infections (Hyperthermia- even hot tub use)
Maternal diabetes
Obesity
Nutrional deficiencies
SSRIs
Zofran (heart defects)
Things that affect whether or not a teratogen affects outcome:
Maternal and infant genotype
Developmental stage at time of exposure
Dose and duration of exposure
Mechanism of action and pathogenesis
Microtia (small ears)
Birth Mark (pigmented area)
May indicate other abnormalities
One = 3% chance of a major defect
Two = 10% chance of a major defect
Three or more =20% chance of a major defect
Prenatal Dx
Ultrasound
Maternal Serum Screening(Alpha-Feto-Protein; AFP)
NTDs, Omphaloceles, Ventral body wall defects, etc.
Down syndrome, Trisomy 18, Sex Chromosome Abnormalities
Non-invasive prenatal screening (NIPS: Cell free DNA)
Amniocentesis(Genetics, AFP, Ach)
Chorionic Villus Sampling (Genetics)
Older women(>35), History of birth defects, Chromosome anomalies
6 week embryo
Two gestational sacs
Neural tube failing to close (spina bifida)
How does folic acid prevent defects?
Dr. Sadler’s lab - believes that it affects DNA synthesis
Otherwise methylation (epigenetic control)
Prevents following defects:
NTDs (up to 70%)
Craniofacial
Urogenital
Cardiac
Trisomy 21 (Down syndrome)
Thalidomide
When would you risk invasive prenatal testing?
If a woman was of advanced maternal age
If there was an abnormal ultrasound or serum screening test
If there was a family history of genetic problems
What percentage of women pregnant with twins actually give birth sucessfully?
30%
End of 8 weeks gestation
What is the difference between small for gestational age (SGA) and intrauterine growth restriction (IUGR)?
SGA means small, but normal: IUGR means exposure to a toxic factor
When an infant is born before surfactant is produced
Neonatal respiratory distress syndrome
**Twin transfusion syndrome
**
Occurs when the placentas of twins grow too close together and begin to share a common blood supply.
What is the most common malformation?
and Rate
Heart defects (1:100)
Most common is VST
Neural tube defects
Rate
1:1000
Cleft palate
Rate
1:700
How does maternal insulin-dependent diabetes induce birth defects?
Combination of toxic factors:
Ketones
Hyper/hypoglycemia
Growth inhibiting substances
What can cause elevated alpha-fetoprotein during gestation?
Omphalocele - a birth defect in which the infant’s intestine or other abdominal organs protrude through a hole in the belly button area and are covered with a membrane.
What growth factor signaling is disrupted by talidomide?
Fibroblast growth factor (FGF)
Limb bud development begins at 4-5 weeks gestation
Increased nuchal translucency indicates genetic disease (commonly seen in Down syndrome)
What organ is most vulnerable to toxic insult after 8 wks gestation?
The brain
Noninvasive prenatal screening
Cell free DNA (cfDNA) from maternal blood
What prenatal screening tests can be performed at 14 weeks gestation?
Percutaneous umbilical blood sampling (PUBS)
Amniocentesis
When can chorionic villus sampling (CVS) be performed?
The 8th week gestation
