Prenatal Growth Defects and Dx

Question 1

When is a baby considered pre-term?

Answer 1

Born before 34 weeks (38 normal pregnancy)

Question 2

When are the organ systems of the fetus well-established?

Answer 2

By the second month of gestation

Question 3

When does the embryo gain the most length and weight?

Answer 3

Length: 3-6 months gestation

Weight: 7-9 months gestation

Question 4

Low birth weight

Answer 4

Less than 5 lbs. 8 oz.

Question 5

SGA and IUGR

Answer 5

Small for gestational age (SGA)

Intrauterine growth restriction (IUGR)

At or below 10th %

Toxic insult/hereditary - one of most common causes is multiple births

Question 6

Barker’s hypothesis

Answer 6

Obesity
Hypertension
Hypercholesterolemia
Type 2 Diabetes
Cardiovascular Disease

(IUGR) - produces problems as adults

Question 7

Twins

Answer 7

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

Question 8

Dizygotic twinning

Answer 8

Two separate embryos, typically separate placentas (sometimes they fuse)

Question 9

Twin transfusion syndrome

Answer 9

One embryo receives too much blood supply the other too little

Question 10

Defects of the primitive streak

Answer 10

Can produce conjoined twins

Question 11

When is the appearance and dissapearance of the herniated gut loop common?

Answer 11

Appearance: wk 6

Dissapearance (reduces): wk 10

Question 12

At what point in gestation is a fetus viable outside of the womb?

Answer 12

7 months (when lungs begin to make surfactant)

Question 13

Types of birth defects

Answer 13

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)

Question 14

Abnormal gene signaling (classification of abnormal fetal development)

Answer 14

Malformation

Question 15

Vascular accidents are classified as what type of malformation during fetal development?

Answer 15

Disruption

Question 16

Amniotic bands

Answer 16

The amnion strands wraps around and constricts blood floow (extrimities)

AER disruption can also produce similar effects

Question 17

Causes of birth defects

Answer 17

Question 18

Microarrays

Answer 18

Specific DNA sequences hybridized to patient’s DNA or RNA. Detects mutations and changes in expression.

Question 19

Exome sequencing

Answer 19

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.

Question 20

Increased incidence of trisomy 21 with increasing maternal age:

Answer 20

Age 25 = 1/2000

35 = 1/300

40 = 1/100

Question 21

Turner syndrome

Answer 21

45 X monosomy

Question 22

Angelman Syndrome

Answer 22

15q11-15q13: maternal deletion (imprinting)

Question 23

Thalidomide

Answer 23

Characteristic limb defects (absence of the long bones)

Question 24

Zika virus

Answer 24

Can cause necrosis of brain tissue (microcephaly)

Question 25

Environmental causes of defects

Answer 25

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)

Question 26

Things that affect whether or not a teratogen affects outcome:

Answer 26

Maternal and infant genotype Developmental stage at time of exposure Dose and duration of exposure Mechanism of action and pathogenesis

Question 27

Microtia (small ears) Birth Mark (pigmented area)

Answer 27

May indicate other abnormalities ## Footnote One = 3% chance of a major defect Two = 10% chance of a major defect Three or more =20% chance of a major defect

Question 28

Prenatal Dx

Answer 28

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

Question 29

Answer 29

6 week embryo

Question 30

Answer 30

Two gestational sacs

Question 31

Answer 31

Neural tube failing to close (spina bifida)

Question 32

How does folic acid prevent defects?

Answer 32

Dr. Sadler's lab - believes that it affects DNA synthesis Otherwise methylation (epigenetic control) ## Footnote Prevents following defects: NTDs (up to 70%) Craniofacial Urogenital Cardiac

Question 33

Answer 33

Trisomy 21 (Down syndrome)

Question 34

Answer 34

Thalidomide

Question 35

When would you risk invasive prenatal testing?

Answer 35

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

Question 36

What percentage of women pregnant with twins actually give birth sucessfully?

Answer 36

30%

Question 37

Answer 37

End of 8 weeks gestation

Question 38

What is the difference between small for gestational age (SGA) and intrauterine growth restriction (IUGR)?

Answer 38

SGA means small, but normal: IUGR means exposure to a toxic factor

Question 39

When an infant is born before surfactant is produced

Answer 39

Neonatal respiratory distress syndrome

Question 40

Answer 40

**Twin transfusion syndrome ** Occurs when the placentas of twins grow too close together and begin to share a common blood supply.

Question 41

What is the most common malformation? | and Rate

Answer 41

Heart defects (1:100) ## Footnote Most common is VST

Question 42

Neural tube defects | Rate

Answer 42

1:1000

Question 43

Cleft palate | Rate

Answer 43

1:700

Question 44

How does maternal insulin-dependent diabetes induce birth defects?

Answer 44

Combination of toxic factors: Ketones Hyper/hypoglycemia Growth inhibiting substances

Question 45

What can cause elevated alpha-fetoprotein during gestation?

Answer 45

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.

Question 46

What growth factor signaling is disrupted by talidomide?

Answer 46

Fibroblast growth factor (FGF) ## Footnote Limb bud development begins at 4-5 weeks gestation

Question 47

Answer 47

Increased nuchal translucency indicates genetic disease (commonly seen in Down syndrome)

Question 47

What organ is most vulnerable to toxic insult after 8 wks gestation?

Answer 47

The brain

Question 48

Noninvasive prenatal screening

Answer 48

Cell free DNA (cfDNA) from maternal blood

Question 49

What prenatal screening tests can be performed at 14 weeks gestation?

Answer 49

Percutaneous umbilical blood sampling (PUBS) Amniocentesis

Question 50

When can chorionic villus sampling (CVS) be performed?

Answer 50

The 8th week gestation