1. Hypertension in Pregnancy
Tony Nicoll
Consultant Obstetrician
Ninewells Hospital

2. Outline Objectives Physiology Classification Pre-eclampsia
Pathogenesis
Management
Eclampsia
Conclusions

3. Objectives
Understand the processes involved in antenatal care, surveillance in pregnancy, and the roles of the professionals involved (Outcomes 1-11)
Demonstrate a knowledge of the common problems encountered in obstetric practice (Outcomes 3,4,5,8)

4. Hypertension in Pregnancy
Hypertension affects 10-15% of all pregnancies
Mild pre-eclampsia affects 10% of primigravid women
Severe pre-eclampsia affects 1% of primigravid women
Eclampsia affects 1/2000 pregnancies
Death from eclampsia = 2%
Pre-eclampsia is the commonest cause of iatrogenic prematurity
Up to 25% of antenatal admissions are due to hypertension

5. Blood Pressure in Pregnancy
Blood pressure (BP) proportional to systemic vascular resistance and cardiac output
Pregnancy  Vasodilatation
BP falls in early pregnancy
Nadir reached at weeks
Steady rise until Term
BP falls after delivery but subsequently rises and peaks at day 3-4 P/N

6. Hypertension DBP >110 mmHg
≥140/90 mmHg on 2 occasions
DBP >110 mmHg
ACOG - >30/15 mmHg compared to booking BP

7. Hypertension in Pregnancy
Pre-existing hypertension
Pregnancy Induced Hypertension (PIH)
Pre-eclampsia

8. Pre-existing Hypertension
Diagnosis prior to pregnancy
Likely if hypertension in early pregnancy
(PET / PIH diseases of second half of pregnancy)
May be retrospective diagnosis if BP has not returned to normal within 3 months of delivery
Consider secondary causes - renal / cardiac, Cushing’s, Conn’s, Phaeochromocytoma
Risks include PET (X2), IUGR and abruption

9. PIH Second half of pregnancy Resolves within 6/52 of delivery
No proteinuria or other features of pre-eclampsia
Better outcomes than pre-eclampsia
15% progression to pre-eclampsia - depends on gestation
Rate of recurrence is high

10. Pre-eclampsia

11. Pre-eclampsia Hypertension Proteinuria (≥0.3g/l or ≥0.3g/24h) Oedema
Absence does not exclude the diagnosis

12. Pre-eclampsia
A pregnancy-specific multi-system disorder with unpredictable, variable and widespread manifestations
May be asymptomatic at time of first presentation
Diffuse vascular endothelial dysfunction widespread circulatory disturbance
Renal / Hepatic / Cardiovascular / Haematology / CNS / Placenta

13. Pathogenesis Genetic predisposition
Stage 1 - abnormal placental perfusion
Stage 2 - maternal syndrome

14. Pathogenesis
Abnormal placentation and trophoblast invasion  failure of normal vascular remodelling
Spiral arteries fail to adapt to become high capacitance, low resistance vessels
Placental ischaemia  widespread endothelial damage and dysfunction
Mechanism unclear (??oxidative stress / PGI2 : TXA2 imbalance / NO)
Endothelial Activation 
 Capillary Permeability
 Expression of CAM
 Prothrombotic Factors
 Platelet aggregration
Vasoconstriction

15. Non- Pregnant
Pre-eclampsia
Normal Placentation

16. A Multi-system Disorder
CNS
Renal
Hepatic
Haematological
Pulmonary
Cardiovascular
Placental

17. CNS Disease Eclampsia Hypertensive encephalopathy
Intracranial haemorrhage
Cerebral Oedema
Cortical Blindness
Cranial Nerve Palsy

18. Renal disease  GFR Proteinuria
 serum uric acid (also placental ischaemia)
 creatinine / potassium / urea
Oliguria /anuria
Acute renal failure
acute tubular necrosis
renal cortical necrosis

19. Liver Disease Epigastric/ RUQ pain Abnormal liver enzymes
Hepatic capsule rupture
HELLP Syndrome
Haemolysis, Elevated Liver Enzymes, Low Platelets
high morbidity/ mortality

20. Haematological Disease
 Plasma Volume
Haemo-concentration
Thrombocytopenia
Haemolysis
Disseminated Intravascular Coagulation

21. Cardiac / Pulmonary Disease
Pulmonary oedema  ARDS
iatrogenic
disorder related
Pulmonary Embolus
High mortality

22. Placental Disease Intrauterine growth restriction (IUGR)
Placental Abruption
Intrauterine Death

23. Symptoms Headache Visual disturbance Epigastric / RUQ pain
Nausea / vomiting
Rapidly progressive oedema
Considerable variation in timing, progression and order of symptoms

24. Signs Hypertension Proteinuria Oedema Abdominal tenderness
Disorientation
SGA
IUD
Hyper-reflexia / involuntary movements / clonus

25. Investigations Urea & Electrolytes Serum Urate Liver Function Tests
Full Blood Count
Coagulation Screen
CTG
Ultrasound - biometry, AFI, Doppler

26. Management Assess risk at booking
Hypertension < 20 weeks - look for secondary cause
Antenatal screening - BP, urine, MUAD
Treat hypertension
Maternal & fetal surveillance
Timing of Delivery
PIH can be managed as O/P in Day Care Unit

27. Risk Factors Maternal Age (>40 years 2X) Maternal BMI (>30 2X)
Family History (20-25% if mother affected, up to 40% if sister)
Parity (first pregnancy 2-3X)
Multiple pregnancy (Twins 2X)
Previous PET (7X)
Molar Pregnancy / Triploidy
Multiparous women develop more severe disease

28. Medical Risk Factors Pre-existing renal disease
Pre-existing hypertension
Diabetes Mellitus
Connective Tissue Disease
Thrombophilias (congenital / acquired)

29. Predicting Pre-eclampsia
Normal MUAD
Notch
Maternal Uterine Artery Doppler
weeks

30. Antenatal Screening When to refer to AN DCU? BP  140/90
(++) proteinuria
  oedema
symptoms - esp persistent headache
For every 1000 “Low-risk” patients:
100 hypertensive
60 normal - 20 will return
20 DCU follow up - 10 admitted
20 admitted

31. When to admit? BP >170/110 OR >140/90 with (++) proteinuria
Significant symptoms - headache / visual disturbance / abdominal pain
Abnormal biochemistry
Significant proteinuria - >300mg / 24h
Need for antihypertensive therapy
Signs of fetal compromise

32. Inpatient Assessment Blood Pressure - 4 hourly Urinalysis - daily
Input / output fluid balance chart
24 hour urine collection - if proteinuria on urinalysis
Bloods - FBC, U&Es, Urate, LFTs. Minimum X2 per week

33. Fetal Surveillance Fetal Movements CTG - daily Ultrasound Biometry
Amniotic Fluid Index
Umbilical Artery Doppler
Normal
AEDF
REDF

34. Treatment of Hypertension
Treat regardless of aetiology
With MAP ≥150 mmHg there is significant risk of cerebral haemorrhage
Most treat if BP ≥150/100 mmHg
BP ≥ 170/110 mmHg requires immediate Rx
Aim for / mmHg
Control of blood pressure does not reduce the risk of developing pre-eclampsia

35. Treatment of Hypertension
Mode of Action
Starting Dose
Maximum Dose
Contra-
indications
Breast Feeding
Methyl Dopa
Centrally acting  agonist
250mg bd
1 gram tds
Depression
Yes
Labetolol
 +  antagonist
100mg bd
600mg qid
Asthma
Nifedipine SR
Ca channel antagonist
10mg bd
40mg bd
Hydralazine
Vasodilator
25mg tds
75mg qid
(Avoid Diuretics / ACE Inhibitors)

36. When to Deliver? The only cure for pre-eclampsia is delivery
Mother must be stablised before delivery
Consider expectant management if pre-term
Most women delivered within 2 weeks of diagnosis

37. Indications for Delivery
Term gestation
Inability to control BP
Rapidly deteriorating biochemistry / haematology
Eclampsia
Other Crisis
Fetal Compromise - REDF, abnormal CTG

38. Crises in Pre-eclampsia
HELLP syndrome
Pulmonary Oedema
Placental Abruption
Cerebral Haemorrhage
Cortical Blindness
DIC
Acute Renal Failure
Hepatic Rupture

39. Steroids Promote fetal lung surfactant production
↓ neonatal respiratory distress syndrome (RDS) by up to 50% if administered 24-48h before delivery
Administer up to 36 weeks
Only significant effects up to 34 weeks. Proven benefit up to 1 week
Betamethasone preferred to Dexamethasone
1 course = 12mg Betamethasone IM X2 injections 24 hours apart

40. Eclampsia

41. Eclampsia
Tonic-clonic (grand mal) seizure occuring with features of pre-eclampsia
>1/3 will have seizure before onset of hypertension / proteinuria
Ante-partum (38%) / Intra-partum (16%) / post-partum (44%)
More common in teenagers
Associated with ischaemia / vasospasm

42. Management of Severe PET / Eclampsia
Control BP
Stop / Prevent Seizures
Fluid Balance
Delivery

43. Antihypertensives IV Labetolol IV Hydralazine
Beware hypotension – fetoplacental unit

44. Seizure Treatment / Prophylaxis
MAGNESIUM SULPHATE
Loading dose: 4g IV over 5 minutes
Maintenance dose: IV infusion 1g/h
If further seizures administer 2g Mg SO4
If persistent seizures consider diazepam 10mg IV

45. Fluid Balance Main cause of death = pulmonary oedema
(Capillary leak / fluid overload / cardiac failure)
Oliguria in 30%. Does not require intervention
Any doubts about renal function  urine osmolality
Fluid challenges are potentially dangerous
Safer to run a patient “dry” - 80 ml/h

46. Labour and Delivery Aim for vaginal delivery if possible Control BP
Epidural anaesthesia
Continuous electronic fetal monitoring
Avoid ergometrine
Caution with iv fluids

47. Postpartum Management
Breast feeding
Contraception
BP management
Counselling
Future risk
Depends on other medical factors
Gestation dependent (28/ %, 32/ %)
Long term CVD risk

48. Low Dose Aspirin
Aspirin - inhibits cyclo-oxygenase  prevents TXA2 synthesis
75mg Aspirin 15%  reduction in PET (NNT=90)
May be more beneficial in preventing severe early onset pre-eclampsia (MRC CLASP Trial)
Safe
Used for high risk women - Renal, DM, APS, Multiple risk factors, previous PET
Commence before 12 weeks
NICE Aug 2010

49. Calcium, Antioxidants & Folic Acid
Calcium supplementation (>1gram / day) may reduce risk of hypertension (30%), PET (52%) and maternal death (20%). Did not affect pre-term birth or stillbirth (Hofmeyr et al Cochrane Database 2006)
Antioxidants not effective (Poston et al. VIP Study, Lancet 2006)
Mid trimester folic acid also appears to be effective in preventing pre-eclampsia (73% reduction) (Wen et al AJOG 2008)

50. Conclusions Hypertension in pregnancy is common
Pre-eclampsia is a multi-system disorder with unpredictable and variable manifestations
Pathogenesis involves abnormal placentation and widespread endothelial dysfunction
Supportive management requires maternal and fetal surveillance
No cure other than delivery
Maternal risks balanced against risks of prematurity