LECTURE - Maternal Serum Screening Flashcards
pregnancy complications on the maternal side
- pre-existing disease = hypertension, autoimmune disease
- ectopic pregnancy
- gestational diabetes
- gestational trophoblastic disease
- mal-presentation at term
- premature or post-term delivery
pregnancy complications - fetal
- anomalies: chromosomal, teratogens, neural tube defects
- amniotic fluid probs: oligohydramnios, polyhydramnios
- hemolytic disease of the newborn
- respiratory distress
pregnancy complications for both maternal and fetal
placental problems = preeclampsia, infection
screening to detect complications early
- 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
these induce birth defects by interfering with normal development
teratogens
list of teratogens
- 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)
how to confirm pregnancy
- 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!)
abnormal # of chromosomes
aneuploidy
T or F. all pregnant women have a small chance of having a pregnancy affected by a trisomy
T; prenatal screning provides an estimate of that chance
trisomy 21
- 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
organ effects of T21
- brain: mental retardation. Alzheimer disease
- heart: septal defects
- GI: bowel atresia
- blood: leukemia
- reproductive: sterility in males
- hypothyroidism, poor muscle tone, hearing + eye problems*
physical characteristics T21
- flat facial profile, slanted eyes, short stature
- Simian crease in palm
- gap between toes
T18
- 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
T13
- 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
Omphalocele
GI organs protrude through belly button in a sac
we need a high screen detection for prenatal screening
75% detection rate; no more than 3% false pos rate in first trimester and no more than 5% false pos rate in 2nd trimester
risk factors for aneuploidy
- advancing maternal age >35 5y/o
- previous affected pregnancy
- parents who are carriers of a genetic translocation
screening reports possible outcomes
- 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
screening vs diagnostic tests
- 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
malformations of baby due to congenital infections
- Rubella
- CMV
- syphilis
- chickenpox
prenatal infections causing long-term disease in infant
- HIV
- Hep B or C
the condition of having an abnormal number of chromosomes
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%
neural tube defects
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
anencephaly
neural tube defect
- absence of brain; cranial vault (RARE but fatal)
encephalocele
neural tube defect
brain protrudes through skull
spina bifida
neural tube defect (spinal cord0
- more common than other two talked about
first trimester combined screen
- 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)
second trimester maternal serum QUAD screen
- serum screen = biochemical markers only; 15w to 20w6d
- AFP
- hCG
- DIA
- uE3
AFP
alpha-fetoprotein
- synthesized by fetal liver
- decreased in T18 an T21
uE3
unconjugated estriol
- steroid secreted by fetal liver and placenta
- decreased in T18 and 21
hCG in second trimester maternal serum screening
- synthesized by trophoblastic cells
- increased in T21
- reduced in T18 and 13
DIA
dimeric inhibin A
- glycoprotein of unknown function
- increased in T21
when is 2nd trimester AFP only screen done?
- 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
ultrasound vs maternal serum AFP
AFP only = detect ONTDs
U/S = can detect both open and closed
non-invasive prenatal screenings (NIPS)
- 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
what is tested in NIPS and how?
- 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
tests available fo prenatal diagnosis
- 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
only diagnostic test available in first trimester
chorionic villus sampling
only diagnostic test available in the second or third trimesters of pregnancy
amniocentesis
Diagnostic Tests (performed after amniocentesis and CVS)
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)
