LECTURE - Maternal Serum Screening

Question 1

pregnancy complications on the maternal side

Answer 1

• pre-existing disease = hypertension, autoimmune disease
• ectopic pregnancy
• gestational diabetes
• gestational trophoblastic disease
• mal-presentation at term
• premature or post-term delivery

Question 2

pregnancy complications - fetal

Answer 2

• anomalies: chromosomal, teratogens, neural tube defects
• amniotic fluid probs: oligohydramnios, polyhydramnios
• hemolytic disease of the newborn
• respiratory distress

Question 3

pregnancy complications for both maternal and fetal

Answer 3

placental problems = preeclampsia, infection

Question 4

screening to detect complications early

Answer 4

• pre-pregnancy: identify infertility + women at risk + lifestyle education + counselling
• early: confirmation of pregnancy + first-trimester prenatal screening + infection and BGs + Abs
• mid: maternal serum prenatal screen, routine ultrasound (~5 months), gestational diabetes screen
• late: prediction of pre-eclampsia

Question 5

these induce birth defects by interfering with normal development

Answer 5

teratogens

Question 6

list of teratogens

Answer 6

• drugs of abuse
• cigarettes
  = toxic metals, poorly controlled metabolic disorders
• radiation
• infections
• meds (use min effective dose or alternative; anticonvulsant = phenytoin, valproate, anticoags like warfain)

Question 7

how to confirm pregnancy

Answer 7

• human chorionic gonadotropin (BhCG)
• lateral flow immunoassays
• urine = detectable 9-11 days after conception; 25-150 IU/L
• plasma = 7-9 days; positive >5 IU/L (more sensitive!)

Question 8

abnormal # of chromosomes

Answer 8

aneuploidy

Question 9

T or F. all pregnant women have a small chance of having a pregnancy affected by a trisomy

Answer 9

T; prenatal screning provides an estimate of that chance

Question 10

trisomy 21

Answer 10

• Down syndrome
• most common naturally occurring chromosomal rearrangement
• 1/800 births
• risk increases with maternal age; ge 40 = 1/100 chance of having live born baby with T21

Question 11

organ effects of T21

Answer 11

• brain: mental retardation. Alzheimer disease
• heart: septal defects
• GI: bowel atresia
• blood: leukemia
• reproductive: sterility in males
• hypothyroidism, poor muscle tone, hearing + eye problems*

Question 12

physical characteristics T21

Answer 12

• flat facial profile, slanted eyes, short stature
• Simian crease in palm
• gap between toes

Question 13

T18

Answer 13

• Edwards syndrome
• 1/7900 births
• high frequency of fetal lost; most live a week or less
• clinical features: dysmorphic, severe developmental delay, heart defects, facial clefts, spina bifida

Question 14

T13

Answer 14

• Patau syndorme
• 1/9500 births
• high frequency of fetal loss; miscarriage, stillbirth, or neonatal death; few survive to 6 mos
• clinical features are severe: dysmorphic, growth retardation, cardiac, kdieny malformations, scalp defects, Omphalocele

Question 15

Omphalocele

Answer 15

GI organs protrude through belly button in a sac

Question 16

we need a high screen detection for prenatal screening

Answer 16

75% detection rate; no more than 3% false pos rate in first trimester and no more than 5% false pos rate in 2nd trimester

Question 17

risk factors for aneuploidy

Answer 17

• advancing maternal age >35 5y/o
• previous affected pregnancy
• parents who are carriers of a genetic translocation

Question 18

screening reports possible outcomes

Answer 18

• screen negative: reduce risk
• screen positive: increased risk; genetic counseling: non-invasive prenatal testing (NIPT), invasive prenatal testing
• at least 5% false pos rate
  > 1 in 20 women will have a positive result
  > most will be false pos

Question 19

screening vs diagnostic tests

Answer 19

• screening = results not definitive; give a risk, risk calc
  > 1st trimester combined screen and 2nd trim QUAD screen
  > asking woman her age; amniocentesis if 35 or older maybe?
  > cell free DNA
• diagnostic = definitive results; karyotyping of fetal cell for aneuploidy (including T21, T18, T13)
  > obtained by CVS or amniocentesis

Question 20

malformations of baby due to congenital infections

Answer 20

• Rubella
• CMV
• syphilis
• chickenpox

Question 21

prenatal infections causing long-term disease in infant

Answer 21

• HIV

- Hep B or C

Question 22

the condition of having an abnormal number of chromosomes

Answer 22

fetal aneuploidy
- can be chromosome number reduction (NOT a viable pregnancy) or increase
- often caused by faults in cell division of the gametes
> meiotic non-disjunction 95%

Question 23

neural tube defects

Answer 23

brain and/or spinal cord failed to develop properly
- during neuralation = neural tube does not close properly

classified as open or closed
- depends on type and thickness of membrane covering the neural tube defect

90% survival to at least age 30

Question 24

anencephaly

Answer 24

neural tube defect

- absence of brain; cranial vault (RARE but fatal)

Question 25

encephalocele

Answer 25

neural tube defect | brain protrudes through skull

Question 26

spina bifida

Answer 26

neural tube defect (spinal cord0 | - more common than other two talked about

Question 27

first trimester combined screen

Answer 27

- T21, 18, 13 - Nuchal translucency + biochemical markers > requires ultrasound: gestational dating and NT > 11w2d to 13w6d - biochemical markers: bhCG and PAPP-A > bhCG = free beta human chorionic gonadotropin > PAPP-A = pregnancy associated plasma protein A (placenta)

Question 28

second trimester maternal serum QUAD screen

Answer 28

- serum screen = biochemical markers only; 15w to 20w6d - AFP - hCG - DIA - uE3

Question 29

AFP

Answer 29

alpha-fetoprotein - synthesized by fetal liver - decreased in T18 an T21

Question 30

uE3

Answer 30

unconjugated estriol - steroid secreted by fetal liver and placenta - decreased in T18 and 21

Question 31

hCG in second trimester maternal serum screening

Answer 31

- synthesized by trophoblastic cells - increased in T21 - reduced in T18 and 13

Question 32

DIA

Answer 32

dimeric inhibin A - glycoprotein of unknown function - increased in T21

Question 33

when is 2nd trimester AFP only screen done?

Answer 33

- pre-pregnancy BMI > or equal to 35 kg/m2 - limited access to ultrasound detection of open neural tube defects elevated maternal serum AFP = requires U/S to check for other conditions

Question 34

ultrasound vs maternal serum AFP

Answer 34

AFP only = detect ONTDs | U/S = can detect both open and closed

Question 35

non-invasive prenatal screenings (NIPS)

Answer 35

- done to decrease unnecessary invasive procedures (decrease false pos); enhance trisomy detection rate (decrease false neg) - for high risk pregnant women > advanced maternal age > positive maternal serum screen > previous pregnancy with chromosomal condition > abnormal U/S findings

Question 36

what is tested in NIPS and how?

Answer 36

- materna blood plasma collected after 10 wks gestation - extracting free fetal DNa fragments to see if there really is problem with child's genotype > quantitative counting or non-quantitative genotyping > targeted or untargeted (PCR, fluorescence, sequencing) **NOT COVERED**

Question 37

tests available fo prenatal diagnosis

Answer 37

- CVS = placenta (11-14 wks) - amniocentesis = amniotic fluid (14+ wks; preferably 16 wks) - gold standard tests = >99% specificity and sensitivity - BUT expensive, requires expertise, invasive (risk of fetal loss 1-2%), blood contamination

Question 38

only diagnostic test available in first trimester

Answer 38

chorionic villus sampling

Question 39

only diagnostic test available in the second or third trimesters of pregnancy

Answer 39

amniocentesis

Question 40

Diagnostic Tests (performed after amniocentesis and CVS)

Answer 40

Chromosome analysis - rapid aneuploidy detection (RAD) > detects aneuploidies on chromosomes 21, 18, 13, and X, Y > quantitative fluorescent PCR on capillary sequencer Ultrasound or Biochemical Measurement for NTD - amniotic fluid AFP (immunoassay) - CSF form of acetylcholinesterase (gel electrophoresis)