Hypertension in Pregnancy Dr Lim Soon Hock MRCOG Sarawak General Hospital
Introduction Hypertensive disorders of pregnancy (HDP) remains as one of common causes of maternal mortality in Malaysia. Accounted for 14.1% of total maternal death between 1997-2000 (Confidential Enquiry of Maternal Mortality, Malaysia 2005) Carry risk for the woman such as eclampsia, DIVC, intracranial bleeding, VTE, pulmonary oedema, heart failure, abruptio placentae and death. Most develop for the first time in the second half of the pregnancy. Carry risk for the baby: higher rate of perinatal mortality, preterm birth and low birth weight.
Basic Stuff Chronic hypertension: Hypertension present at booking visit or before 20 weeks, or that is being treated at time of referral to maternity services. Can be primary or secondary in aetiology. Gestational hypertension: New hypertension presenting after 20 weeks without significant proteinuria.
Basic Stuff Eclampsia: Convulsive condition associated with pre-eclampsia. Pre-eclampsia: New hypertension presenting after 20 weeks with significant proteinuria. Severe pre-eclampsia: Pre-eclampsia with severe hypertension and/or with symptoms, and/or biochemical and/or haematological impairment. Significant proteinuria: urinary protein:creatinine ratio >30mg/mmol or 24 hour urine collection >300mg/day.
Risk factors for pre-eclampsia Moderate First pregnancy Age ≥ 40 years Pregnancy interval > 10 years BMI ≥ 35 kg/m2 at first visit Family history of pre-eclampsia Multiple pregnancy
Risk factors for pre-eclampsia High Hypertensive disease during previous pregnancy Chronic kidney disease Autoimmune disease such as systemic lupus erythematosis or antiphospholipid syndrome Type 1 or type 2 diabetes Chronic hypertension
If at least 2 moderate risks factors or one high risk factor for PET Advise woman to take aspirin 75 mg/day from 12 weeks until birth**NICE Hypertension in pregnancy August 2010
Evidence Cochrane systematic review of 59 RCTs involving 37 560 women was conducted to determine the effectiveness of antiplatelet agents (mainly aspirin) in reducing the risk of preeclampsia and its complications.**Duley L, Henderson-Smart DJ, Meher S et al. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database of Systematic Reviews 2007;(2)CD004659.
Evidence antiplatelet agents were associated with a statistically significant reduction in the risk of pre- eclampsia (RR 0.83; 95% CI 0.77 to 0.89). Antiplatelet agents were associated with a statistically significant reduction in the risks of preterm birth before 37 weeks (RR 0.92; 95% CI 0.88 to 0.97) and fetal and neonatal deaths (RR 0.86; 95% CI 0.76 to 0.98).
A meta-analysis using individual-patient data assessed the effectiveness of antiplatelet agents (mainly aspirin) in risk reduction for pre-eclampsia (N= 32217 women, 32819 babies) showed a statistically significant reduction in risk of developing pre-eclampsia (RR 0.90; 95% CI 0.84 to 0.97).* *Askie LM, Duley L, Henderson-Smart DJ et al. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet 2007; 369:(9575)1791-8.
Points worth noting: NNT: 114 to prevent one case of PET. 10% reduction in pre-eclampsia in high-risk women receiving antiplatelet agents. 10% reduction in preterm birth. No difference between those who started before or after 20 weeks.
Is aspirin safe? There were no statistically significant differences between women receiving antiplatelet agents and those receiving placebo in the incidence of potential adverse effects such as antepartum haemorrhage, placental abruption or postpartum haemorrhage* *Askie LM, Duley L, Henderson-Smart DJ et al. Antiplatelet agents for prevention of pre- eclampsia: a meta-analysis of individual patient data. Lancet 2007; 369:(9575)1791-8.
Outline of Management of Pre-eclampsia (PET) Antihypertensives: Aim for BP<150/80-100mmHg. First-line: labetalol (oral, IV) Second-line: Nifedipine, methyldopa Monitor BP every 4 hours, hourly if severe HPT. Check FBC, PT/PTT, BUSE, Se Creatinine, Se Uric acid.
Outline of Management of Pre-eclampsia (PET) Fetal Monitoring: USS for fetal growth + AFI + Umbilical artery doppler every 2 weekly. CTG: at diagnosis and repeat if reduced fetal movement, PV bleeding, abdo pain, deterioration of maternal condition Steroids: IM dexamethasone 12mg BD for 2 doses if considering delivery within 7 days (24 to 36 weeks) for fetal lung maturity.
Outline of Management of Pre-eclampsia (PET) Timing of delivery: Determine by several factors: Severe refractory hypertension Deteriorating maternal or fetal conditions. Availability of neonatal care. Completion of corticosteroid. After 37+0 weeks: recommend birth within 24-48 hours.
Magnesium sulphate Magpie trial (Lancet 2002,N= 10,141) Significantly fewer eclamptic fits (0.8% Vs 1.9% with placebo) - 58% lower relative risk of eclampsia. A significant reduction in maternal mortality (0.2% Vs 0.4% with placebo) - 45% reduction in relative risk. Significantly lower risk of placental abruption (2% Vs 3.2% with placebo)
Indications for MgSO4 Give intravenous magnesium sulphate if woman with severe hypertension or severe pre-eclampsia has or previously had eclamptic fit. Consider giving intravenous magnesium sulphate* if birth planned within 24 hours in woman with severe pre-eclampsia.
Features of severe pre-eclampsia Severe hypertension and proteinuria or mild or moderate hypertension and proteinuria with at least one of: severe headache problems with vision such as blurring or flashing severe pain just below ribs or vomiting Papilloedema signs of clonus (≥ 3 beats) liver tenderness HELLP syndrome platelet count falls to < 100 x 10 9 /litre abnormal liver enzymes (ALT or AST rises to > 70 iu/litre).
Cochrane systematic review(6 RCT, n = 11,444) magnesium sulphate was statistically significantly better than none/placebo in preventing eclampsia (RR 0.37- 0.44) No statistically significant differences in : maternal death, serious maternal morbidity, pulmonary oedema, placental abruption, kidney dialysis, stillbirth and neonatal death rates.* Duley L, Gulmezoglu AM, and Henderson-Smart DJ. Magnesium sulphate and other anticonvulsants for women with preeclampsia. Cochrane Database of Systematic Reviews 2008;(3).
MgSO4 regime* Loading dose of 4 g given intravenously over 5 minutes, followed by infusion of 1 g/hour for 24 hours. Further dose of 2–4 g given over 5 minutes if recurrent seizures.*The Eclampsia Trial Collaborative Group (1995)Which anticonvulsant for women with eclampsia?Evidence from the Collaborative Eclampsia Trial.Lancet 345:1455–63.
Outline of Management of Pre-eclampsia (PET) Fluid balance: limit fluid to 2L/day (total) Mode of delivery: according to clinical circumstances and woman’s preference.
Postnatal care Breastfeeding: No known adverse effects: labetalol, nifedipine, enalapril, captopril, atenolol, metoprolol. Insufficient evidence on safety: ARBs, amlodipine, ACE inhibitors other than enalapril & captopril.
Next pregnancy? Risk of PET: ranges from 1 in 14 to 1 in 2. If birth before 34 weeks: 1 in 4. If birth before 28 weeks: 1 in 2.