Pregnancy, prenatal and neonatal testing Flashcards
What are the clinical indications for measuring hCG?
pregnancy
gestational
trophoblastic disease and other malignancies
prenatal screening for fetal aneuoploidies
exogenous hCG (doping, hCG suppl from internet sources, munchausen syndrome)
hCG is actually a pretty complex molecule. Why?
It’s a dimer with a unique 145 aminoa acid beta subunit and a 92 amino acid alpha subunit that is identical to that of LH, FSH and TSH
but there are actually 5 bioactive forms of hCG, plus degradation products of each of these circulating in the serum/found in urine
What are the sources of hCG in the body?
pregnancy is the most common
pituitary
Gestational trophoblastic disease or testicular germ cell tumors
What would be the issue with using the alpha subunit of hCG for a pregnancy test?
it’s not specific to pregnancy since it would also be high in situatiosn with elevated LH, FSH and TSH
When do total and hyperglycosylated hCG levels peaks in pregnancy?
around 10 weeks, but this can vary
Which form of hCG is predominant in early pregnancy? What does this mean for testing?
hCG-H - some assays are not as effective at detecting this form, so you can get false negatives
Which forms of hCG are produced by malignancies?
beta forms (also not as effectively detected by some assays)
Qualitative hCG tests only give you a positive/negative answer. What level is typically flagged as positive?
between 10-50 iU/L
Do the qualitative tests detect hCG degradation products?
No - it does not reliably detect degradation products, so the test may have reduced reactivity in urine after 8 weeks gestation (since it will have peaked and start degrading)
Quantitative hCG tests will give you a numerical amount and typically have a detection limit down to what?
2 IU/L
Do the quantitative hCG tests measure degradation products?
yes, but vary widely in the forms of hCG being detected
When a patient’s period is less than a week late, what is the best pregnancy test?
SERUM hCG instead of urine
What is the median for hCG level at 4 weeks GA?
72 mIU/ml
We say that hCG should double every 29-53 hours during the first 30 days after implantation, but what is the actual typical increase?
85% of women will have a rise of 65% or more in 48 hours
What is the differential diagnosis for persistently low levels of hCG?
- spontaneous abortion/resolving ectopic
- biochemical pregnancy
- quiescent or (ess likely) active gestational trophoblastic disease
- pituitary hCG (can look elevated by be normal)
- Other tumors (bladder, uterine, lung, liver, pancreas stomach)
- Ingestion of hCG
- Familial hCG syndrome
- False positive on initial test
If someone has a positive serum hCG, but negative urine hCG, what are the potential causes?
Differing sensitivity of urine and serum assays (obvious one)
False positive on the serum hCG
“phantom hCG” - humans can generate human anti-human antibodies that cross-react with and bind animal antibodies used in hCG testing so you can get a false positive
These false positive serum hCG assays are particularly common in what group of patients”
those with IgA deficiency (false positive pregnancy test in about 30% of them)
In the “phantom hCG” false positive serum hCG assays, why doesn’t the urine assay also show a false positive?
the interfering antibodies are too large to be filtered into the urine.
Singleton pregnancies usually peak around what hCG level?
100,000 but this varies widely
What is the differential diagnosis for an hCG over 100,000?
multiple gestations
gestational trophoblastic disease (40% of complete moles will have hCG over 100,ooo)
When should a doctor initiate an infertility workup?
after 1 yr of unprotected sex for a woman less than 35 yoa
after 6 mo for women over 35
(or earlier if she has known risk factors for infertility)
What is the initial test that should be done in the evaluation for male infertility?
semen analysis
What parameters are looked at in a semen analysis?
ejaculate volume pH sperm concentration total sperm number percentage motility forward progression normal morphology sperm agglutination viscosity
What are the main causes of female infertility?
Ovulatory dysfunction (25%) endometriosis pelvic adhesions tubal blockage other tubal abnormalities hyperprolactinemia
What are some causes of ovulatory dysfunction?
PCOS obesity weight gain/loss strenuous exercise thyroid dysfunction
How can ovulatory function be evaluated?
- ask about menstrual history (if they have hx of abnormal bleeding, oligo, or amenorrhea, then they can be diagnosed with ovulatory dysfunction without further testing)
- serum progesterone (made by corpus luteum after ovulation, so if it’s low, then suggests ovulatory dysfunction)
when during the cycle should the progesterone be measured?
approximately 1 week prior ot expected menses (which is when it peaks) - this is why if a women has abnormal periods, she can get the diagnosis without testing
What hormone surges 36-40 hours prior to ovulation?
LH - which is why patients can use OTC urinary LH ovulation predictor kits
What additional hormones should you measure if progesterone is low?
TSH and prolactin to identify thyroid disorder ro hyperprolactinemia
FSH and estradiol
What pattern of FSH and estradiol will be seen in primary ovarian failure?
high FSH and low estradiol
What pattern of FSH and estradiol will be seen in hypothalamic amenorrhea?
low FSH, low estradiol
What is ovarian reserve?
reproductive potential as a function of quality and quantity of oocytes
Why is ovarian reserve measured?
Measure it because women with decreased ovarian reserve will have diminished response to ovarian stimulation and it might not be worth the effort
How can you measure ovarian reserve?
measure with a cycle day 3 FSH and E2 (high FSH, or nl FSH with high E2 predict poor response)
Anti-mullerian hormone (low predicts poor response)
Antral folicle count (using transvaginal US in early follicular phase)
clomiphene citrate challenge test (measure FSH before and after)
What is the differential for hypertension in pregnancy?
chronic hypertension
gestational hypertension
preeclampsia-eclampsia
What are the diagnostic criteria for preeclampsia?
BP > 140/90 on 2 occations at least 4 hr apart after 20 wks GA OR >160/110 once
AND
> 300 mg 24 hr urine protein OR protine/cr over 0.3 OR dipstick reading of 1+
How do chronic hypertension vs gestational hypertension differ?
chronic HTN is HTN that predates pregnancy or began BEFORE 20 weeks GA
gestational is after 20 weeks (without proteinuria or other ecclampsia features)
What are the severe features that can accompany preeclampsia?
BP 160/110 on 2+ occasions at least 4 hr apart while pt on bedrest
plt < 100,000
impaired LFTs
Cr over 1.1 or doubling
pulmonary edema
cerebral or visual disturbances (new)
What labs should be run if you have concenr for preeclampsia?
plts
creatinine
AST/ALT
can do blood smear, LDH, bilirubin
What are the diagnostic criteria for HELLP syndrome?
microangiopathic hemolytic anemia with schistocytes on smear
Plt < 100,000
TBili over 1.2
AST over 70
What should be done next after a diagnosis of HELLP has been made?
Deliver the baby! Right away if over 34 weeks, give steroids first if less than 34 weeks
In patients with preeclampsia without severe features, what lab testing is recommended for routine monitoring?
weekly assessment of Plt count and liver enzymes
When should the newborn screening take palce?
between 24-48 hrs of age
How should the newborn screen be obtained?
heel stick
What are the criteria for inclusion of a disorder in the newborn screening panel?
significant morb/mortality available treatment time before symptoms onset clincially valid screen cost-beneficial natural hx of disease understood known and significant incidence in population being screened
What labs should you get for screening a patient in an acute metabolic crisis?
ammonia CBC with diff glucose ABG electrolytes BUN, creatinine Uric acid
What are the logistics of an ammonia draw?
needs to be put on ice immediately and run ASAP (hemolysis and delayed processing will all elevate the ammonia)
