Pregnancy Monitoring Flashcards
Where is hCG produced? What is its structure?
hCG - human chorionic gonadotropin
Chorion — contains trophoblasts which produce hCG and other placental hormones
Peak production 8-10 weeks
Structure
- a and b subunits, non-covalently bound
- Glycoprotein — branched CHO side chains
- a subunit same as TSH, LH, FSH
MW = 14900
- b subunit like LH b
MW = 23000
- In plasma, free a, free b, CGn and CGbCF
- Urine mainly CGbCF, some intact hCG, some CGn
State the clinical utility of glucose tolerance test.
Performed at 24-28 weeks gestation
- Overnight fast of at least 8 h
- 75 g consumed within 5 mins
- Blood collection before drink, then 1 hr and 2 hr after drink finished
- Any cutoff value exceeded is diagnostic of GDM
➔ Fasting > or = 5.1 mmol/L
➔ 1 hr > or = 10 mmol/L
➔ 2 hr > or = 8.5 mmol/L
Difference with regular oral glucose tolerance test
➔ Additional 1 hr sample
➔ Lower glucose cutoffs
- Increased insulin secretion & enhanced tissue sensitivity to insulin
- Placenta metabolizes/transport 50-75% of maternal glucose
State the clinical utility of fetal fibronectin test.
Used to test for preterm labour
- Extracellular protein that glues chorion to decidua
- POCT
Sensitivity = 70%
Specificity = 90%
+ve Test = 50% chance of preterm labour
-ve Test = 95% chance of no delivery
ALL patients who come for assessment for possible preterm labour
➔ 90% have no delivery in next 7 days
What are the endocrine changes that occur during pregnancy?
- Shift to supply nutrients to fetus
- Preparation of maternal physiology for
- Maintenance of pregnancy
- Delivery
- Lactation
What is needed to mediate the endocrine changes that occur during pregnancy?
Corpus luteum — estrogen & progesterone
Placenta — Hormones, cytokines
Fetal hormones
What is the mechanism to initiate hormonal changes in pregnancy?
Embryo implantation induces trophoblast differentiation into HCG producing cells
- HCG maintains corpus luteum beyond 2 weeks
- Placenta becomes major source of estrogen & progesterone
Placental Inhibin A production
- Suppress pituitary LH, FSH ➔ no gonadal development during pregnancy
What does the placenta provide the fetus with? What does the mother require during pregnancy?
Healthy placenta provides fetus with
- Amniotic fluid
- Nutrients — glucose, aa, lipids, minerals, trace elements, vitamins
- Adequate gas exchange
- Clearance of toxic metabolic products — bilirubin, urea, ammonia
Health mother must acquire
- Nutrient stores
- Protection against blood loss in delivery
What are the maternal adaptive mechanisms?
- Plasma volume expansion
- Altered cardiac output and blood flow
- Increase GFR
- Expanded erythrocyte mass
- Hepatic protein synthesis
What are the hormonal changes that take place in pregnancy?
- Progesterone for early embryonic growth is 5-20x above non-pregnant women
- Estrogens (estrone, estradiol, estriol)
- Placental-peptide hormones
- hCG — human chorionic gonadotropin
- hPL/hCS — placental lactogen or chorionic somatomammotropin
What is progesterone produced by during pregnancy? What is the function?
Produced: 1st corpus luteum (50 d), then placenta
Function
- *Inhibits smooth muscle tone
- Vascular impact — peripheral vascular smooth muscle tone resulting from decreased sensitivity to angiotensin II
- Stimulates hyperventilation — respiratory alkalosis
What is the action of estrogens during pregnancy?
- Endometrial development
- Blood supply
- Uterine muscle growth — preparation for delivery
- Hepatic protein synthesis
What is E3 a marker for?
Fetal and placental well being
What is a polypeptide similar to growth hormone during pregnancy? Function?
Placental lactogen
- Spares glucose for fetal utilisation
What is hCG function?
- Maintain corpus luteum function
- binds to ovarian LH receptor - a subunit acts in signal transduction (via cAMP)
- promote progesterone production required for maintaining endometrium - hCG > 1000000 U/L is thyrotropic
- hCG can bind and activate TSH receptor
What are the hemodynamic changes in pregnancy?
- Total body water increase 4-6 L
- Blood volume 45% increase
- Dilutional effect on some analytes
- Net decrease in Hgb concentration
- Low Hgb results in lower viscosity
What are the causes of plasma volume increase?
- Anatomic changes
➔ decrease in vascular smooth muscle tone due to progesterone — low blood pressure - Renin-angiotension-aldosterone axis
➔ activated to compensate for low BP
➔ estrogens incr liver synthesis of angiontensiongen
➔ incr water retention
What changes does the heart go through in pregnancy?
- Cardiac output increases 30-40%
- Extra flow mainly goes to uterus/placenta
What changes does the kidney go through in pregnancy?
- Renal blood flow increases 50%
- GFR 50% above non-pregnant by 20 weeks
- Plasma urea and creatinine lower
- Tubular reabsorption of glucose, aa, protein decr
What changes does the lungs go through in pregnancy?
- Respiration stimulated by progesterone
- Respiratory alkalosis
- Slight decrease in pCO2, HCO3 ➔ incr pH
What is the most common liver disease of pregnancy? List when presentation occurs, what is the clinical presentation, pathobiology, risk, treatment.
Intrahepatic Cholestasis of Pregnancy
Presentation
- Late second or early trimester
- Generalized itching, initially palms of hands and soles of feet, fat malabsorption, steatorrhea, Vit deficiency
Pathobiology: unclear — bile acid transporter genes in liver and high estrogen co-contribute: subsequent pregnancy 60-70% recurrence
Risk: Intrauterine fetal demise, spontaneous preterm birth or stillbirth
Treatment — ursodeoxycholic acid (UDCA)
What is the most sensitive indicator of intrahepatic cholestasis of pregnancy (ICP)? What are other indicators?
Most sensitive ➔ total bile acids (umol/L, fasting)
- May increase >10x in ICP
Other ➔ cholic acid
- less commonly available
- may increase >10x in severe cases of ICP
How to diagnose and date pregnancy?
Physical examination
1. History — last menstrual period
2. Ultrasound — dating optimal 8-14 weeks
3. Physical exam
Laboratory
1. Urinary hCG (qualitative) — 25 IU/L detected 1 week after missed period
➔ do this test if u would like to know
2. Serum hCG (quantitative) — 5 IU/L (8-11d post-conception)
➔ do this test if NEED to know definitively now
When is hCG detectable?
3 1/2 weeks when placenta produces measurable hCG
What are the pregnancy diagnostic pitfalls?
Lack of sensitivity of an hCG test — false negative
1. Pre-analytical
- mislabel, dilute urine, urine test too early
2. Analytical
- test Ab is relatively insensitive to hyperglycosylated form of hCG
3. Post-analytical
- reporting error
Lack of specificity of hCG test — false positive
1. Pre-analytical
- mislabel, sample collected on a peri/post menopausal women, patient with hCG producing tumour, early pregnancy loss, fertility treatment
2. Analytical
- Heterophilic Ab (serum)
- Historical — post menopausal woman w/ very high LH had cross reactivity with hCG test
3. Post-analytical
- reporting error
What is ectopic pregnancy? How to detect ectopic pregnancy?
Implantation occurs outside uterus, usually fallopian tube
- Ectopic pregnancies are not normally viable
- Risk of rupture leading to internal bleeding, death is rare
Detection
- Clinical symptoms of ectopic pregnancy ➔ abdominal pain, bleeding
- Diagnostic imaging
➔ no gestational sac on U/S 24 d after conception if dating known
➔ no gestational sac if serum hCG > 3000 IU/L
- hCG may be low or undetectable
- Normal ➔ doubling time every 48h for first 5 weeks, after 5 weeks doubling time increases to 2-3 d
How to differentiate ectopic/non-viable pregnancy from normal pregnancy?
On a graph (y-axis = hCG, x-axis = time)
- Bigger slope = normal
- Smaller slope = ectopic/non-viable
What is gestational diabetes? What are the complications? How to identify? Treatment?
Diabetes of pregnancy
Complications for fetus:
1. Large fetus
2. Sudden intrauterine death
3. Neonatal death from prematurity
4. Respiratory distress syndrome
5. Newborn hypoglycemia
Complications for mother:
1. 20-50% chance of mother developing type 2 diabetes within decade
Identify with obstetric glucose tolerance test.
Manage with lifestyle therapy (insulin in overt cases)
What are the clinical issues of preterm labour?
- Impt to transfer mother to an appropriate medical centre if pre-term delivery expected to allow access to:
- Neonatal specialists
- Incubators
- Ventilators - Difficult to predict which patients will go into labour
- Traditional tests may not be definitive
