Pregnancy Monitoring Flashcards
1
Q
What are forms of Pregnancy Monitoring?
A
Non-biochemical monitoring
- US, foetal heartbeat, bp, weight gain
Biochemistry
- Monitoring of at-risk patients for diabetes, thyroid disease, liver disease
- Testing in pregnancy for ectopic pregnancy, hydatidiform mole and choriocarcinoma
- Monitoring pre-existing conditions during pregnancy
2
Q
What are the implications of Pregnancy on Reference ranges?
A
- Increased volume of distribution
- Increased binding proteins
- Increased requirements
3
Q
What happens to calcium in Pregnancy?
A
- Total calcium falls due to physiological hypoalbuminaema
- Free ionised calcium does not change
- Placenta produces 1,25-dihydroxyvitamin D resulting in increased absorption of calcium from the gut
- Calcium is actively transported across the placenta, facilitated by PTH-rP
- Foetal calcium homeostasis depends mostly on PTHrP
4
Q
Who are the patients that need to be monitored in Pregnancy?
A
- Diabetes
- Thyroid disease
- Liver disease
- Pre-eclampsia syndrome
5
Q
What is Gestational Diabetes?
A
- Any degree of glucose intolerance resulting in hyperglycaemia with the onset during pregnancy
- Screen at 24-28 weeks
6
Q
What are risk factors for Gestational Diabetes?
A
- Weight BMI>30 kg/m2
- Family history of DM (1o relative)
- Previous macrosomic baby >4.5 kg
- Ethnic origin esp Asian, Black Caribbean
- Previous GDM
7
Q
How is Gestational Diabetes diagnosed?
A
- Patients with risk factor oGTT at 24-28 weeks
- (prev GDM, initial oGTT, rpt at 24-28 wks if normal)
- Definition of GDM includes previous categories of gestational impaired glucose tolerance and GDM
- Fasting glucose >5.6; 2hr glucose >7.8 mmol/L (N.B. can’t use HbA1c for diagnosis, or fasting glucose)
8
Q
What is the treatment for Gestational Diabetes?
A
- Diet, exercise, metformin, insulin as required
- Weight loss advice for BMI >28 kg/m2
- Maintain fasting glucose <5.3mmol/l, 2hr post- prandial <7.8mmol/L
9
Q
What are possible causes of Gestational Diabetes Mellitus?
A
Human placental lactogen (hPL) – rises from 6th week of pregnancy to peak at approx 23 weeks
- Increases breakdown of maternal fat to increase fatty acids as energy source (glucose for foetus)
- Increase in insulin release from pancreas (poss increase in peripheral resistance)
10
Q
What are thyroiid diseases in Pregnancy?
A
Hyperthyroidism - differential diagnosis:
- Hyperemesis gravidarum
- Thyroid disease (Usually Graves, affects approx 1:1500 pregnancies)
Hypothyroidism
- Hashimoto’s thyroiditis
N.B. Post partum thyroiditis
11
Q
What is Post Partum Thyroiditis?
A
- Develops within a couple of months of birth
- Transient hyperthyroid followed by hypothyroid state, resolves spontaneously without treatment
12
Q
Whya re thryoid hormones affected by Pregnancy?
A
hCG
- Weak thyroid stimulating action of hCG due to structural similarity with TSH. The beta subunit of both molecules are similar. Has 1/10,000th of activity of TSH
- See clinical effects if hCG>200 U/L for several weeks (note hCG>25U/L consistent with pregnancy)
- Can see slightly low TSH, high normal free T4/T3 in first trimester when hCG highest
TBG
- Total T4/T3 affected by increased TBG in pregnancy caused by oestrogen
13
Q
Why does hCG have the same effect as some Pituitary Hormones?
A
- hCG, TSH, LH, FSH have common alpha subunit
- hCG and TSH structurally similar beta subunit
14
Q
What is Hyperemesis Gravidarum?
A
- Excessive vomiting in pregnancy”
- Usually first trimester
- Asians greater incidence than caucasians
- Believed to be related to high hCG, aetiology unknown
- Most cases spontaneously resolve by second trimester
15
Q
How is Hyperemesis Gravidarum differentiated from other thyroid disorders?
A
- Can be difficult to distinguish between HG and thyrotoxicosis as 2/3 are transiently biochemically hyperthyroid
- TRABs negative in HG, positive in Graves’ disease
- Generally managed with fluid replacement, rarely require beta blockers or anti-thyroid meds
16
Q
What are features of Obstetric cholestasis?
A
- Liver disorder unique to pregnancy; describes association between liver dysfunction and pruritus
- Occurs in third trimester but pathogenesis still unknown.
- Genetic element
- Role of oestrogen as highest in third trimester – cases also described
- Affects approx 0.7 % pregnancies, (1.2-1.5% Asian pregnancies)
17
Q
What are symptoms and investigations of Obstetric Cholestasis?
A
- Pruritus (itch) common in pregnancy (23% affected)
- Obstetric cholestasis should be suspected in cases of pruritus of unexplained origin in absence of a rash, esp palms of hands or soles of feet, with abnormal LFTs and/or raised bile acids
- If LFT/bile acids normal repeat 1-2 weekly as pruritis may predate rise.
18
Q
What are risk factors for Obstetric Cholestasis?
A
- Previous history (45-90% recurrence)
- Family history
- Multiple pregnancies
19
Q
What are adverse foetal outcomes for Obstetric Cholestasis?
A
- Increased intrauterine mortality
- Increased spontaneous (and iatrogenic) premature birth
- Increase intracranial haemorrhage secondary to vitamin K deficiency (fat soluble vitamins affected by disordered bile acid metabolism)
20
Q
What is the treatment for Obstetric Cholestasis?
A
- Topical
- Antihistamines
- Ursodeoxycholic acid (+vit K)
- Conservative management (monitoring weekly)
- Consider elective delivery from 37 weeks
21
Q
What happens post partum in Obstetric Cholestasis?
A
Repeat 2wks, if LFT/bile acids still increased at 8wks refer
22
Q
Describe Bile Acid biochemistry
A
- Family of acidic sterole based of C24 cholaninc Acid.
- Synthesised from cholesterol in the liver to form primary bile acids
- 7-alpha hydroxylation is rate limiting tep in bile acid synthesis
- Amphilic compounds – hydrophilic underside & hydrophobic topside
- Conjugated with glycine or taurine (decrease pKa)
23
Q
What is the function of Bile Acids?
A
Function as biological detergents:
- Solubilise cholesterol & lipids in bile
- Emulsification & absorption of dietary fat (Vit K)
24
Q
What are Biochemistry results for patients with Obstetric Cholestasis?
A
- Bile acids >14 umol/L
- AST/ALT/γGT may be raised
- bilirubin usually normal (jaundice rare)
- ALP rise due to pregnancy isoform
- In absence of other cause of liver disease e.g. pre eclampsia, viral esp hep C, alcohol, gallstones, autoimmune
- Other investigations viral hep A,B,C, EBV,CMV; AMA, ASMA; urine PCR; bp; liver US
25
What is HELLP syndrome?
* Haemolysis
* Elevated Liver Enzymes
* Low Platelets)
26
What are features of HELLP syndrome?
* Affects 0.2-0.6% pregnancies
* Affects 10-20% women with pre eclampsia
* Cause unknown ?separate condition or severe form of pre eclampsia
* Usually presents at \>37 weeks but may present post partum
* 1:4 risk of recurrence with future pregnancies
27
What are the biochemistry results for HELLP syndrome?
* **Haemolysis:** Fractured red cells on blood film (LDH \>600 IU/L) [Ref range 20-220IU/L]
* **Liver Enzymes:** AST/ALT \>70 IU/L, (increases morbidity/mortality if \>150) [Ref range 5-45 U/L]
* **Bilirubin:** often increased
* **Low Platelets:** need to distinguish from gestational thrombocytopenia where platelet count drops to 7-150 x 109/L in 2nd/3rd trimester
CT scan may show bleeding in liver
28
What are complications of HELLP syndrome?
* DIC (disseminated intravascular coagulation)
* Pulmonary oedema
* Renal failure
* Liver haemorrhage and failure
* Placental abruption
29
What is the treatment for HELLP syndrome?
* Delivery, may require transfusion
* Affects may continue post partum
30
What are features of Acute Fatty Liver of Pregnancy?
* Rare life-threatening disorder presenting in 3rd trimester or post-partum
* Thought to be due to disordered metabolism of fatty acids caused by a deficiency in the mitochondrial LCHAD (long chain 3-hydroxyacyl coenzyme A dehydrogenase) enzyme
* Mortality 10-20% maternal, 20-30% foetal
31
What is the biochemstry of Acute fatty liver of pregnancy?
* Bilirubin increased
* Liver enzymes (AST/ALT): typically, \>1000 IU/L (may be 300-500)
* May also present with hypoglycaemia, raised WCC
* Liver US may show fat deposition in liver
32
What is Pre eclampsia syndrome?
* Maternal syndrome of hypertension, proteinuria and oedema part of a severe systemic inflammatory response.
* Although mechanism remains unclear, a major cause is the failure to develop an adequate blood supply to the placenta, leading to placental oxidative stress.
* (See a rapid disappearance of clinical signs or symptoms following delivery of the placenta
33
How is diagnosis of Pre-Eclampsia syndrome made?
* Proteinuria (300 mg/d mild to severe \>5g/d) [Ref range \<150mg/d] or urine PCR\>30mg/mmol [Ref \<3]
* with blood pressure \>140 mmHg systolic; or \>90 mmHg diastolic on 2 separate occasions
Other associated findings are Hyperuricaemia
34
How are Placental Biomarkers produced?
* Biomarkers produced by the trophoblastic cells of the placenta and pass into the maternal bloodstream where they can exert effects on the maternal metabolism.
* Production of the placental biomarkers may be altered in placental dysfunction, so the concentration in maternal serum has the potential to be used clinically in the investigation of patients.
35
What are some Placental Biomarkers?
* **PlGF** (placental growth factor)
* **sFlt-1** (soluble fms-like tyrosine kinase-1)
* **sFlt-1:PlGF** **ratio**
36
What are features of PlGF (placental growth factor)?
* Angiogenic hormone, 46-50kDa, involved in remodelling of arteries in uterus to increase blood supply to placenta (angiogenesis = growth of blood vessels)
* In normal pregnancy, rises in maternal circulation peaking at 26-30 weeks, falling towards delivery
* Lower concentrations associated with pre eclampsia
* Can be measured with sFlt-1 (soluble fms-like tyrosine kinase-1
37
What are features of sFlt-1 (soluble fms-like tyrosine kinase-1)?
* Anti-angiogenic protein.
* Truncated form of the VEGF receptor-1 (Flt-1) (VEGF= vascular endothelial growth factor)
* Flt-1 binds both VEGF and PlGF
* sFlt is important in blood vessel regulation in tissues such as kidney, uterus and cornea
* Found to be abnormally increased in pre-eclampsia
38
What does sFlt-1:PlGF ratio tell us?
High concentrations both of sFlt and sFlt:PlGF ratio associated with pre-eclampsia
39
How does Pre-Eclampsia develop?
* Placental ischemia results in the release of antiangiogenic factors (sFtl-1), which bind to vascular endothelial growth factor (VEGF) and placental growth factor (PlGF)
* This prevents their interaction with their native high affinity kinase receptors on the vascular endothelium.
* The resultant endothelial dysfunction prevents the development of an adequate blood supply.
* Pre-eclampsia may be mediated, in part, by this imbalance of circulating angiogenic factors.
40
What is Ectopic Pregnancy?
* When foetus develops outside uterus usually in Fallopian tube
* Affects approx 1% pregnancies
41
What are the risk factors of Ectopic Pregnancy?
* IUDs, progesterone only OCP, tubal ligation
* Previous ectopic pregnancy (10-20% recurrence)
* Pelvic, abdominal, tubal surgery
* Previous PID
* IVF, Ovulation induction
42
How does Ectopic Pregnancy present?
* 30% present prior to missed period
* Pain (lower abdo)
* May have positive pregnancy test
* If ruptured then profuse bleeding into pelvis, vaginal bleeding insignificant leading to hypovolaemic shock (deaths in UK 0.2% of ectopic pregnancies, 2015)
* Suspect if any of risk factors present
43
How is an Ecotpic Pregancy Diagnosed?
* Vaginal ultrasound can detect intrauterine pregnancy
* In absence of intrauterine pregnancy may be miscarriage (vaginal bleeding should proceed pain) or ectopic pregnancy
* hCG typically \<1000 IU/L although can present higher
* Normally at least double every 2.3d, lack of increase (but no decrease) suggests ectopic
* Progesterone suggested (cut-off \<48 or \<70 nmol/L) as low in ectopic, negative predictive value poor
44
What is the treatment for Ectopic Pregnancy?
* Spontaneous abortion or degenerating ectopic usually managed conservatively
* Methotrexate can be used to halt foetal growth
* Surgical laparotomy may be required
* Emergency if rupture- surgery plus fluid replacement
45
What are features of Hydatidiform mole (gestational) and Choriocarcinoma trophoblastic neoplasia?
* After surgery to remove mole 20% complete moles require further surgery or chemotherapy
* Can develop into invasive moles or choriocarcinoma (8%)
* Choriocarcinoma most frequently develops from complete moles but can occur after normal pregnancy or early foetal loss
* More likely to metastasize
* All moles go on National Hydatidiform Register (monitor hCG 99% sensitivity and specificity)
46
What are features of Gestational trophoblastic neoplasia (GTN)?
* Tumours which develop in the trophoblast cells surrounding the embryo
* Can develop following a molar pregnancy or a normal pregnancy
* Molar pregnancy cannot produce normal foetus
* Suspect in bleeding in early pregnancy or in cases of persistent bleeding post delivery
47
What is the most common types of GTN?
* Hydatidiform mole (molar pregnancy)
* \<16 and \>40 yrs most common, approx 1:1000
* Moles are villi resembling bunches of grapes
48
What are complete and partial moles?
* **Complete mole:** When sperm fertilises an empty egg containing no nucleus or DNA
* **Partial mole:** When 2 sperm fertilise an egg (too much DNA). Rarely become malignant or require further treatment
49
How is Diagnosis of Hydatidiform mole (molar pregnancy) made?
* High serum hCG (can be up to 6,000,000 IU/L)
* Ultrasound
50
How are pre-existing conditions monitored during pregnancy?
* Any drug therapies stopped if contra-indicated or alternatives found
* Monitoring of long term conditions more closely as pregnancy may exacerbate disorder. Increased volume of distribution or requirements
51
How is Diabetes monitored as an example?
* Increased risk to mother of pre eclampsia, miscarriage, preterm labour; risk to foetus of congenital defects, macrosomia, birth injury, perinatal mortality.
* Advise HbA1c \<48 mmol/mol (\<6.5%) pre conception
* Fasting blood glucose 5-7mmol/L, other times of day 4-7mmol/L
* Stop oral hypoglycaemics, replace with metformin or insulin
