Obstetric Medicine 1 - Medical disorders in pregnancy

Question 1

What are overall physiological changes in pregnancy?

Answer 1

Increased Plasma Volume
Increased Cardiac Output
Increased Stroke Volume
Increased Heart Rate
Increased DBP/SBP
Decreased TPVR

Question 2

What are changes in renal physiology in pregnancy?

Answer 2

Effective renal plasma flow and glomerular filtration rate increase from ~10/40

70% increase in renal blood flow, plethoric kidney swells
Increased bipolar diameter 1cm
Increased GFR (50%)
Proteinuria increases (L

Question 3

What is the definition of hypertension in pregnancy?

Answer 3

Systolic >140 or diastolic >90 on >=3 readings
Severe >160/110
High risk of maternal morbidity and mortality, need for immediate treatment

Normal BP in preg - 111.5/65.2 at 12/40
115/69 by 37/40

Question 4

What are classification of hypertension in pregnancy?

Answer 4

Preeclampsia-eclampsia 41%
Gestational HTN (36%) - after 20/40
Chronic HTN
 - essential 15%
 - 2ndary 5%
 - white coat
Pre-eclampsia + chronic HTN 3%

Question 5

What was the outcome of the CHIPS study wrt HTN control in prengnacy?

Answer 5

Pts with non-proteinuric gestational or pre-gestational HTN
Compared tight and less tight BP control (DBP160/110)

Found that metyldopa was superior to labetalol in primary outcome, BP control and PET

Question 6

What are appropriate antihypertensive medications in pregnancy?

Answer 6

Methyl dopa - central
Clonidine - central
Labetalol - b-blocker, mild alpha vasodilator
Oxprenalol - b-blocker with sympathomimetic activity
NIfedipine - Ca channel blocker
Prazosin - alpha blocker
Hydralazine - vasodilator

Question 7

What is the effect of pregnancy on the metabolism of certain antihypertensive medications?

Answer 7

Increased CYP2D6 metabolism of metoprolol, propranolol and clonidine
Increased CYP3A4 metabolism of nifedipine and amlodipine
Increased conjugation to glucoronide of B-isomer of labetalol

these changes may require increase in dosing frequency

Question 8

What are recommended treatment options for severe, sustained HTN in pregnancy (acute lowering of BP)?

Answer 8

Labetalol - 20-80mg, IV bolus over 2 minutes, repeat every 10 minutes
Nifedipine - 10-20mg tablet, max 40mg
Hydralazine IV bolus
Diazoxide - IV rapid bolus

Question 9

What are features of proteinuria in pregnancy?

Answer 9

Important sign of underlying renal disease
Useful in the Dx of PET - proteinuria presence should determine management - level of proteinuria less critical (not a marker of severity of PET)

Proteinuria does increase in pregnancy - 300mg/24hrs ULN, spot prot:creat ratio 0.03 g/mmol

There is increased permeability in the GBM in the 3rd trimester, proteinuria at baseline doubles in pregnancy

Question 10

What are epidemiological features of pre-eclampsia?

Answer 10

5% of pregnancies
worldwide 50k maternal deaths/year
cured by delivery
30% of cases occur post partum

Question 11

What is the definition of pre-eclampsia?

Answer 11

New onset HTN >20/40, accompanied by >=1 of:
renal involvement
 - proteinuria >0.03g/mmol
 - raised creatinine >90umol/L
 - oliguria

Question 12

What is pathogenesis of PET?

Answer 12

1) Genetic factors, abnormal trophoblast/decidual interaction, oxidative stress and increased AT1 autoantibodies
2) failure of physiological transformation of myometrial segment of spiral artery - defective deep placentation - placental dysfunction
3) oxidative and endoplasmic reticulum stress, proinflammatory CKs, increased AT1 autoantibodies, syncitiotrophoblast microparticles and nanoparticles
4) leads to increase in antiangiogenesis (sVEGFR-1, sEndoglin) and decreasd angiogenesis (PIGF, VEGF)
5) leucocyte and endothelial cell activation and end organ damage

Question 13

What are biomarkers implicated in PET?

Answer 13

VEGF/PLGF
Increased levels of SFLT1 and sENG are implicated in failed interaction of TGF-B1 and VEGF with ALK5, TBRII and ENG and FLT1

sFlt-1:PlGF ratio

Question 14

What are risk factors for PET?

Answer 14

nulliparous women
35yo
Hx of PET in prev pregnancy
Multi-foetal gestation
Obesity
FHX of PET
Pre-existing chronic HTN, DM, APL, Thrombophilia, AID, renal dz, infertility
Limited sperm exposure
Urinary Tract infection

Question 15

What is the treatment of PET?

Answer 15

delivery if >34 weeks
Expectant if safe to do so
High risk signs:
- uncontrolled severe HTN
- HELLP
- renal dysfunction
- eclampsia
- severe IUGR
- pulmonary oedema
Prevent eclampsia with MgSO4 (NNT=300 overall, much lower in high risk patients)

Question 16

What are preventative measures for PET?

Answer 16

Aspirin daily 12% decrease in risk, stillbirth and IUGR - greatest benefit in highest risk

L-arginine and Vit C/E promisin
Ca supplementation in Ca deficiency

New and exciting

• pravastatin increase angiogenic factors, andioxidant and anti-inflammatory
• Plasmapharesis - removal of sFLT1 and sEndoglin
• VEGF
• PPIs - upregulate haemoxygenase
• sleep apnoea and CPAP
• Melatonin

Question 17

What are long-term sequelae of PET?

Answer 17

higher risk of CVD
HTN OR 3.13
CVD OR 2.29
CVA 1.76
ESRF 4.70
Diabetes 1.8

higher risk of metabolic syndrome in growth restricted infants

Question 18

What are pre-pregnancy issues in patients with CKD?

Answer 18

control BP
 - switch to methyldopa, labetalol, nifedipine
 - stop ACE/ARB - malformations at all trimesters
 - alter immunosuppression
 - assess baseline proteinuria
in pregnancy
 - BP control
 - aspirin and calcium
 - anticoagulation

Question 19

What is the relationship between foetal outcomes and renal function?

Answer 19

Significantly worsened rates of SGA, permature delivery and NICU in patients with worsening renal function (TOCOS study)

Question 20

What is the pattern of renal deterioration during CKD pregnancies?

Answer 20

In pts with creat >180 at conception

• 50% stable
• 30% decline during pregnancy and after
• 8% worse during pregnancy and recover 6/12 post partum
• 10% decline 6/52 to 6/12 post partum

Question 21

What is the relationship between stage I CKD and outcomes

Answer 21

Outcomes have been shown to be poor in women with only mild CKD (stage I)

Question 22

When should A/C be considered in patients with CKD and pregnancy?

Answer 22

When albumin 3gm/protein/24 hrs

Question 23

What is the benefit of nocturnal haemodialysis in pregnancy?

Answer 23

Increases time of dialysis - in pts receving >36 hrs dialysis vs

Question 24

What are relative outcomes of pregnancy in renal transplant patients?

Answer 24

88% live births, 10% spontaneous abortions, 2% stillbirths

Question 25

What are conditions of pregnancy post transplant?

Answer 25

Generally >1year post transplant Stable renal function Off teratogenic medications Infective risk low (CMV)

Question 26

What are teratogenic immunosuppressive agents in pregnancy?

Answer 26

cyclosporin, tacrolimus, steroids

Question 27

What immunosuppressant agents are safe in pregnancy?

Answer 27

Calcineurin inhibitors - cyclosporin, tacrolimus - no increase in malformations - no LT learning or behavioural difficulties - HTN and DM issues Azathioprine safe - crosses placenta - foetus lacks enzyme to convert to 6 mercaptopurine STOP ACE AND ARBs

Question 28

What are different issues with liver and renal transplant pregnancies?

Answer 28

Liver transplant pregnancies more likely to be successful Higher rates of rejection post partum in liver transplants. Higher rates of unsuccessful pregnancies in renal transplants, in addition to PET, IUGR, early delivery

Question 29

What immunomodulatory agents are safe in breast feeding?

Answer 29

azathioprin, tacrolimus, cyclosporin expressed at low levels in breast milk ?ok NO lt f/u studies at present

Question 30

What is the relationship between immunity and pregnancy?

Answer 30

may act as a sensitising agent 50% of women have HLA Ab post pregnancy should avoid blood transfusions

Question 31

What are significant issues with SLE and pregnancy?

Answer 31

Active lpus Lupus nephritis - HTN, renal impairment Ro and La Ab - CHB Antiphospholipid syndrome - clots Can cause - increased lupus activity - pre-eclampsia - IUGR - early delivery - foetal death

Question 32

What are prognostic signs in lupus nephritis and pregnancy?

Answer 32

outcomes are worse even in quiescent disease Poor prognostic signs: - hypertension - high creatinine - proteinuria >1g - active disease

Question 33

What are outcomes in SLE and pregnancy?

Answer 33

Unsuccessful pregnancy 23% | Premature birth

Question 34

What are methods of differentiating between PET and SLE renal flare?

Answer 34

``` Casts/RBCs absent in urine in PET No involvement of skin or joints in lupus Urate generally elevated in PET LFTs rarely deranged in SLE C3 and C4 low in lupus Andi-dsDNA elevated in lupus ```

Question 35

What are features of Ro/La Ab in SLE and pregnancy?

Answer 35

30% of lupus population Assoc with photosensitivity, raynauds, sjogrens Causes CHB 2% in children, neonatal lupus in 5% (no sequalae with neonatal lupus)

Question 36

What are clinical features of ApL

Answer 36

Thrombosis - arterial or venous Pregnancy related: - 3 consec miscarriages with nil chromosomal abn or other maternal cause) - neonatal death after 10 weeks due to placental insufficiency - delivery

Question 37

What are laboratory features of ApL?

Answer 37

aCL IgG and or IgM at high titre, >=2 occasions, 12/52 apart LA +Ve >=2 occasions, 12/52 apart anti-B2-GP Ab >99th centile, >=2 occasions, 12/52 apart

Question 38

What is the management of ApL in pregnancy?

Answer 38

In pts who are preg and have lab evidence only, LD-ASA In patients with ApL and venous/art thrombosis - LMWH and aspirin APL with foetal loss, PET or IUGR - LMWH 40mg and aspirin in pts with APL and recurrent foetal loss - ASA pre preg, LMWH with ASA intraparutm, add steroids if loss whilst on ASA and clexane

Question 39

What SLE medications are OK in pregnancy/lactation?

Answer 39

``` NSAIDS (avoid after 32/40) plaquenil corticsteroids cyclosporine/tacrolimus Azathoprine ``` Heparin ASA

Question 40

What SLE medications are C/I in pregnancy?

Answer 40

MMF (also not in BF) MTX (also not in BF) Cyclophosphamide (also not in BF) Warfarin (ok in BF)

Question 41

What is the utility of hydroxychloroquine in pregnancy?

Answer 41

decreases incidence of flares, including renal flares safe in pregnancy/lact improves hypoglycaemia, lowers lipids, protect OP anti-thrombotic effects ? role in reducing cardiomyopathy in CHB and Ro positive

Question 42

What is the safety of biological agents in pregnancy?

Answer 42

no increase in adverse outcomes no increase in congenital malformations no increase in RR of infections in 1st life avoid live vaccines in 1st year of life

Question 43

What are maternal respiratory changes?

Answer 43

Increase in alveolar ventilation Increase in minute ventilation Increase in tidal volume Mild increase in resp rate, plateaus at 20 weeks pH increases, PaO2 increases then falls to level below peak, but above baseline, PaCO2 drops (30)

Question 44

What are common respiratory Sx in pregnancy?

Answer 44

``` Dyspnoea common (70%), in T2-3 talking and sitting issues, reduced exercise tolerance ```

Question 45

What are features of asthma in pregnancy?

Answer 45

12% pregnant women have asthma 1/3 stable, 1/3 improve, 1/3 worsen poor control leads to PET, IUGR and early delivery Budesonide is class A oral C/S when indicated Symbicort/seretide if moderate/severe asthma

Question 46

What are features of thromboembolism in pregnancy?

Answer 46

Increased risk in pregnancy Increases procoagulant factors, decreases inhibitors 1-2/1000 pregnancies, with 5x antepartum risk Higher risk post-partum (10-20x) DVTs are more common antepartum, equal risk T1-T2, most risk 1st 6 weeks postpartum. 70% left sided, ileofemoral, post phebitic syndrome PE most risk post-partum

Question 47

When is prophylactic A/C indicated antepartum?

Answer 47

``` High risk of thrombosis: - Past Hx of unprovoked DVT/PE - Past Hx provoked DVT/PE i.e OCP - past hx DVT/PE ante/post partum - High risk thrombophilia with +ve FHx (homo FVL, Homo PT gene mutation) APLS, poor obstetric Hx ``` Prevention post partu: - Higher risk ++ - all of the above - high risk thrombophilia with nil FHx - past Hx DVT (provoked or unprovoked) - risk factor profile

Question 48

When is full dose AC indicated antepartum?

Answer 48

warfarin pre-pregnancy recurrent clots - thrombophilia w clots, APLS, prosthetic valves Use LMWH, as warfarin teratogenic (high risk HVs) crosses placenta - hare lip, bone abnormalities, foetal haemorrhage safe postpartum

Question 49

What are highest risk factors for Pregnancy associated VTE?

Answer 49

Immobility OR 10.1 Active medical illness 8.7 Pre-eclampsia 5.8 Other important factors Age >35, obesity (OR 5.3), smoking Varicose veins, planned casesarian section If >3 RFs - recommend prophylaxis

Question 50

What are highest risk thrombophilias for PA-VTE?

Answer 50

``` AT deficiency (in pts w FHx) - 18% FVL homozygous w FHx- 17% ``` Also FVL/prothrombon mut compount hetero, protein C, protein S deficiency

Question 51

What are Dx methods in PA-VTE/PE?

Answer 51

D-dimer - no std ref ranges, not recommended DVT - comp USS - Sn 97, Sp 94 (72% are ileofemoral in pregnancy) - If -ve and clinical suspicion, anticoagulate and repeat doppler 1 week (can consider MRI direct thrombus imaging, or venography) For PE - CXR then V/Q scan - Normal NPV 99%, high prob PPV >85% Low prob VQ and high clin suspicion - negative doppler, can CTPA (10% inc breast ca) or anticoagulate and repeat test in 1 week

Question 52

What are examples of pregnancy specific liver disorders?

Answer 52

Hyperemesis HELLP/PET Intrahepatic cholestasis AFLP

Question 53

What are general changes in LFTs in pregnancy?

Answer 53

decreased albumin and increased ALP

Question 54

What are features of hyperemesis gravidarum?

Answer 54

0.3-2% of pregnancies NV, wt loss >5%, fluid and electrolyte disturbances 1st trimester 50-60% have liver involvement - ALT 2-5 x, usually Bile acids and bili normal RFs - inc BMI, DM, multiple pregnancies, molar pregnancies, hyperthyroidism

Question 55

What are features of HELLP (atypical presentation of PET)

Answer 55

Thrombocytopenia, elevated liver enzymes (200-2000 ALT, AST), haemolysis (Intravascular) - LDH >600 70% antepartum, 3rd trimester, 30% post S+Sx - NV, RUQ discomfort 80%, tenderness, PET in 70% of cases.

Question 56

What is the pathology of HELLP?

Answer 56

endothelial activation platelet aggregation fibrin deposition in sinusoids, necrosis and haemorrhage

Question 57

What are complications and treatment of HELLP?

Answer 57

Complications - liver infarction, haematoma (fever, LDH >2000), fetal abruption, prematurity, death Treat with delivery and MG Recurrence in 30-40%

Question 58

What are features of acute fatty liver of pregnancy?

Answer 58

Mat mortality 1.4% Perinatal mortality 104/100,000 3rd trimester ``` More common if: 1st and multiple pregnancy male foetus low BMI (20%) disorders of fatty acid metabolism (LCHAD) heterozygous mum and heterozygous fetus (FA major source of energy for foetus) ```

Question 59

What are featuers of fatty acid oxidation disorders?

Answer 59

AR LCHAD most common - short and medium chains FAO dis increase incidence of maternal liver disease Long chain disorders x50 risk of maternal liver disease - 79% change of AFLD or HELLP - increase incidence of cholestasis and hyperemesis x12 time risk with short and medium chain dz Follow-up LFTs, glucose Screen FAO disorders - carnitine (free and total), acylcarnitine profile

Question 60

What is Dx criteria for AFLP?

Answer 60

``` >=6 of: vomiting abdo pain polydipsia/polyuria encephalopathy high bili hypoglycaemia high uric acid leucocytosis ascites/bright liver on USS HIgh AST/ALT high ammonia renal impairment coagulopathy microvesicular steatosis on liver Bx ```

Question 61

What are Bx findings in AFLP?

Answer 61

hepatocytes have clear cytoplasm or many vacuoles consistent with steatosis' features consistent with steatohepatitis

Question 62

What is Mx of AFLP?

Answer 62

``` multidisciplinary team early delivery once stable correct coagulopathy/hypoglycaemia NAC/?PLEX preparation for transplanation 20% recurrence in future pregnancies no long term liver disease screen infants for hypoglycaemia consider genetic testing ```

Question 63

What are features of intrahepatic cholestasis of pregnancy?

Answer 63

``` 2nd 1/2 or T3 of preg, normal post itch palms and soles increase in bile acids >10 (Fasting) abnormal AST >20ULN GGT and bili normal jaundice not common (10-15%) benign - mostly resolves post partum higher risk of cholecystitis, cirrhosis, pancreatitis and AI hepatitis cholestasis with oral contraceptives recurrence in future pregnancies ```

Question 64

What is the pathophysiology of intrahepatic cholestasis of pregnancy?

Answer 64

Genetic susceptibility (scandinavians and sth americans) 15% have MDR3 mutation FA ox disorders higher risk hep C, twins, age >35 role of sulphated progesterone metabolites

Question 65

What are foetal implications in intrahepatic cholestasis of pregnancy?

Answer 65

``` increased risk of: - premature delivery - meconium liquor - resp distress - still birth >40 BA level = increased risk bile acids are toxic ```

Question 66

What is treatment of intrahepatic cholestasis of pregnancy?

Answer 66

topical menthol, avoid heat ursodeoxycholic acid - decreases BA levels and progesteroene metabs - improves LFTs and is superior to cholestyramine, steroids dex, cholestyramine, s adenosine methionine, rifampicin

Question 67

What is the utility of UDCA in ICP?

Answer 67

decreases pruritis, pre-term labour, meconium stained liquor, resp distress and NICU admissions, ? no change in stillbirth

Question 68

When is treatment with antivirals indicated in hep B +ve pregnancy?

Answer 68

>10^6 means must treat with TDF to decrease viral load from 32/40 - 6-8 weeks post partum

Question 69

What is the rate of HCV infection (vertical)

Answer 69

only occurs in PCR +Ve women - negible if VL undet >10^7 = high risk 1/3 early in utero, 40-50% late in utero/delivery >15% are infected at birth - 20% spontaneous resolution as per aduts. 5.8% is final rate (1/20) no treatment per se - avoid invasive procedures

Question 70

What are cutoffs for procedures in thrombocytopenia?

Answer 70

``` >150 normal >100 not uncommon, nil issues >80 - epidurals, spinal > 50 instrumented delivery >20 - spont bleeding ```

Question 71

What are features of gestational thrombocytopenia?

Answer 71

``` 5-6% of pregnancies ? dilution/immune/sequestration 90% have >100, can fall to 70 Dx of exclusion - normal counts T1-2, recurs with pregnancy, normalised post partum no increase of thrombocytopenia in baby ```

Question 72

What are features of ITP in pregnancy?

Answer 72

common in age group 5% causes of thrombocytopenia in pregnancy risk of IgG transmission to foetus - thrombocytopenia/IC haemorrhage maternal plt count doesnt predict foetal plt count treatment pre delivery/with bleeding (aim >80) - pred - IVIg - Imuran/splenectomy/rituximab

Question 73

What are normal haemodynamic changes in pregnancy?

Answer 73

BV increased 40-50% during pregnancy - autodiuresis post Heart rate increases 10-15/min CO increased 30-50% preg, extra 50% labor BP decreased 10mmhg SV inc in T1-2, dec in 3rd - increased in labor SVR - decreased pregancny, increased labor

Question 74

What are risk IV conditions for pregnancy?

Answer 74

PAH of any cause Severe LV dysfunction 45mm aorta Aortic dilatation >50mm with bicuspid valve native severe coarctation

Question 75

What are risk III conditions in pregnancy?

Answer 75

``` Mechanical valve Systemic right ventricle Fontan circulation Cyanotic heart disease Other complex congenital disease Aortic dilatation 40-45mm Marfans, 45-50mm in aortic disease with bicuspid valve ```

Question 76

What are risk in mechanical heart valves in pregnancy?

Answer 76

greater risk of complications and mortality balance risk of thrombosis vs bleeding clexane 6-14 weeeks, warfarin if high risk of thrombosis unfractionated heparin at delivery aspirin factor Xa monitoring

Question 77

What are outcomes of recent studies in GDM?

Answer 77

ACHOIS - treatment decreases risk of complications from 4% to 1% HAPO - perinatal risks are increased even with normalised values LANDON - treatment of mild GDM reduces risk of macrosomia, shoulder dystocia, PET and CS

Question 78

What are diagnostic criteria for GDM?

Answer 78

Fast venous PG >=5.1 1hr post venous >=10 2hr venous PG >=8.5 Any one of above

Question 79

What are recommendations for vaccination in pregnancy?

Answer 79

single dose of pertussis for all pregnant women in T3 | influenza for all pregnant women

Question 80

What are features of thyroid disorders in pregnancy?

Answer 80

``` thyroid requirements incr by 30% foetus produces endogenous T4 by 20 weeks hCG stimulates TSHr Hyperthyroidism/hypothyroidism postpartum thyroiditis ```

Question 81

What happens to TSH in pregnancy?

Answer 81

TSH falls in T1 and increases during pregnancy (opposite of hCG)

Question 82

What are upper limits of TSH in pregnancy?

Answer 82

T1 - 2.5 T2 - 3 T3 - 3.5

Question 83

What are definitions of OH and SCH in pregnancy?

Answer 83

OH - TSH elevated to >2.5 or decreased FT4 TSH >=10 regardless of FT4 SCH - TSH between 2.5-10 with normal FT4

Question 84

What are requirements for iodine in pregnancy?

Answer 84

220ug/d pregnancy 290 ug/day lactation need pregnancy mulitvitamins

Question 85

What are features of hypothyroidism in pregnancy?

Answer 85

``` overt hypothyroidism: - impaired foetal cognitive and neuropsych development - miscarriage, IUGR, PET - treat to target TSH range subclinical hypothyroidism - miscarraige - more controversial - ? premature delivery, neurocognitive deficits -- treatment if TPO Ab positive - overtreated at present ```

Question 86

What are features of thyrotoxicosis in pregnancy?

Answer 86

low TSH - High T3, T4 - hyperemesis, mole - grave's is commonest cause of thyrotoxicosis in reporductive years - if TSHr Ab positive - risk of neonatal thyrotoxicosis Treatment - FT4 upper limit of normal - PTU 1st trimester (risk of fatal hepatotoxicity) - CBZ/MMI - 2nd and 3rd trimester, post partum - applasia cutis, choanal and oesophageal atresia.