Obstetric Medicine 1 - Medical disorders in pregnancy Flashcards
What are overall physiological changes in pregnancy?
Increased Plasma Volume Increased Cardiac Output Increased Stroke Volume Increased Heart Rate Increased DBP/SBP Decreased TPVR
What are changes in renal physiology in pregnancy?
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
What is the definition of hypertension in pregnancy?
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
What are classification of hypertension in pregnancy?
Preeclampsia-eclampsia 41% Gestational HTN (36%) - after 20/40 Chronic HTN - essential 15% - 2ndary 5% - white coat Pre-eclampsia + chronic HTN 3%
What was the outcome of the CHIPS study wrt HTN control in prengnacy?
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
What are appropriate antihypertensive medications in pregnancy?
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
What is the effect of pregnancy on the metabolism of certain antihypertensive medications?
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
What are recommended treatment options for severe, sustained HTN in pregnancy (acute lowering of BP)?
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
What are features of proteinuria in pregnancy?
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
What are epidemiological features of pre-eclampsia?
5% of pregnancies
worldwide 50k maternal deaths/year
cured by delivery
30% of cases occur post partum
What is the definition of pre-eclampsia?
New onset HTN >20/40, accompanied by >=1 of: renal involvement - proteinuria >0.03g/mmol - raised creatinine >90umol/L - oliguria
What is pathogenesis of PET?
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
What are biomarkers implicated in PET?
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
What are risk factors for PET?
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
What is the treatment of PET?
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)
What are preventative measures for PET?
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
What are long-term sequelae of PET?
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
What are pre-pregnancy issues in patients with CKD?
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
What is the relationship between foetal outcomes and renal function?
Significantly worsened rates of SGA, permature delivery and NICU in patients with worsening renal function (TOCOS study)
What is the pattern of renal deterioration during CKD pregnancies?
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
What is the relationship between stage I CKD and outcomes
Outcomes have been shown to be poor in women with only mild CKD (stage I)
When should A/C be considered in patients with CKD and pregnancy?
When albumin 3gm/protein/24 hrs
What is the benefit of nocturnal haemodialysis in pregnancy?
Increases time of dialysis - in pts receving >36 hrs dialysis vs
What are relative outcomes of pregnancy in renal transplant patients?
88% live births, 10% spontaneous abortions, 2% stillbirths
What are conditions of pregnancy post transplant?
Generally >1year post transplant
Stable renal function
Off teratogenic medications
Infective risk low (CMV)
What are teratogenic immunosuppressive agents in pregnancy?
cyclosporin, tacrolimus, steroids
What immunosuppressant agents are safe in pregnancy?
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
What are different issues with liver and renal transplant pregnancies?
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
What immunomodulatory agents are safe in breast feeding?
azathioprin, tacrolimus, cyclosporin expressed at low levels in breast milk ?ok
NO lt f/u studies at present
What is the relationship between immunity and pregnancy?
may act as a sensitising agent
50% of women have HLA Ab post pregnancy
should avoid blood transfusions
What are significant issues with SLE and pregnancy?
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
What are prognostic signs in lupus nephritis and pregnancy?
outcomes are worse even in quiescent disease
Poor prognostic signs:
- hypertension
- high creatinine
- proteinuria >1g
- active disease
What are outcomes in SLE and pregnancy?
Unsuccessful pregnancy 23%
Premature birth
What are methods of differentiating between PET and SLE renal flare?
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
