Hypertension in Pregnancy Tony Nicoll Consultant Obstetrician Ninewells Hospital

Outline Objectives Physiology Classification Pre-eclampsia Pathogenesis Management Eclampsia Conclusions

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)

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

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 22-24 weeks Steady rise until Term BP falls after delivery but subsequently rises and peaks at day 3-4 P/N

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

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

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

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

Pre-eclampsia

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

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

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

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

Non- Pregnant Pre-eclampsia Normal Placentation

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

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

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

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

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

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

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

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

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

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

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

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

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

Predicting Pre-eclampsia Normal MUAD Notch Maternal Uterine Artery Doppler 20 - 24 weeks

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

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

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

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

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 140-150/90-100 mmHg Control of blood pressure does not reduce the risk of developing pre-eclampsia

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)

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

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

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

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

Eclampsia

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

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

Antihypertensives IV Labetolol IV Hydralazine Beware hypotension – fetoplacental unit

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

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

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

Postpartum Management Breast feeding Contraception BP management Counselling Future risk Depends on other medical factors Gestation dependent (28/40 - 40%, 32/40 - 30%) Long term CVD risk

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

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)

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