Prevention of pre-eclampsia
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Transcript of Prevention of pre-eclampsia
PREVENTION OF PREECLAMPSIAROLE OF ASPIRIN AND CALCIUM
Dr Kanddy
O&G Updates
Miri Hospital
1/11/14
DEFINITIONS
• Chronic hypertension
• Hypertension (BP ≫140
90mmHg; 4 – 6 hours apart); < 20 weeks of gestation
• Gestational hypertension
• Hypertension (BP ≫140
90mmHg; 4 – 6 hours apart); > 20 weeks of gestation
• Without significant proteinuria
• Pre – eclampsia
• Hypertension (BP ≫140
90mmHg; 4 – 6 hours apart); > 20 weeks of gestation
• With significant proteinuria – urine dipstick 2+ or more; or 24 hours urine protein 300 mg per day or more
• Eclampsia
• Seizure associated with pre-eclampsia
• Chronic hypertension with superimposed pre-eclampsia
• Unclassified hypertension
• Hypertension (BP ≫140
90mmHg; 4 – 6 hours apart); > 20 weeks of gestation but no
BP record prior to that
Based on ISSHP 2001 (International Society for Study of Hypertension in Pregnancy)
PATHOPHYSIOLOGY
• Unknown
BURDEN OF PRE-ECLAMPSIA• One of the major cause of
maternal mortality
MATERNAL MORTALITY - MALAYSIA
• Fetal/neonatal morbidity/mortality
• 1 in 20 (5%) stillbirths occurred in women with pre-eclampsia
• 8 – 10% of all preterm birth result from hypertensive disorders
• Small for gestational age
REDUCING THE RISK OF HYPERTENSIVE DISORDERS IN PREGNANCY
• Pre-existing risk factors
• Modifiable
• Obesity
• Non-modifiable
• Medical illnesses
• Age
• Primiparity
• Family history
ANTIPLATELET AGENTS
• Rational
• Pre-eclampsia is associated with deficient intravascular production of prostacyclin (a vasodilator) and excessive production of thromboxane – a vasoconstrictor and stimulant of platelet aggregation
• Antiplatelet agents – might prevent or delay development of pre-eclampsia
• Evidence
• Before CLASP TRIAL
• Small trials of antiplatelet therapy
• Reduction of about three-quarters in the incidence of PE
• Some avoidance of IUGR
CLASP TRIAL
• Multicentre study
• 9364 women – randomly assigned 60 mg aspirin or matching placebo
• 74% entered for prophylaxis of pre-eclampsia
• 12% for prophylaxis of IUGR
• 3% for treatment of IUGR
• Results
• Use of aspirin was associated with a reduction of only 12% in the incidence of proteinuric pre-eclampsia (not significant)
• No significant effect on the incidence of IUGR or stillbirth and neonatal death
• Significantly reduce the likelihood of premature delivery (19.7% vs 22,2%; p=0.004)
• Was not associated with a significant increase in placental haemorrhages or bleeding during epidural anaesthesia
• Safe for the fetus and newborn infant
• Conclusion
• Do not support routine prophylactic or therapeutic administration of antiplatelet therapy in pregnancy to all women at increased risk of pre-eclampsia or IUGR
• May be justified in women judged to be especially liable to early onset PE severe enough to need very preterm delivery
• All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent were included
• To assess the effectiveness and safety of antiplatelet agents for women at risk of developing pre-eclampsia
• Participants were pregnant women at risk of developing pre-eclampsia
• Results
• 59 trials (37,560 women) included
• 17% reduction in the risk of pre-eclampsia associated with the use of antiplatelet agents; RR 0.83; NNT 72
Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-
eclampsia and its complications. Cochrane Database of Systemic Reviews 2007.
• Significant increase in the absolute risk reduction of pre-elampsia for high risk compared with moderate risk women
• 8% reduction in relative risk of preterm birth; NNT 72
• 14% reduction in fetal or neonatal death
• 10% reduction in small-for-gestational age babies
• Conclusion
• Antiplatelet agents have moderate benefits when used for prevention of pre-eclampsia and its consequences
Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-
eclampsia and its complications. Cochrane Database of Systemic Reviews 2007.
RECOMMENDATION
• Advice women at high of pre-eclampsia to take 75 mg of aspirin daily from 12 weeks until birth of baby
• High risk factors (any one of the following)
• Hypertensive disease during a previous pregnancy
• Chronic kidney disease
• Autoimmune disease such as SLE or antiphospholipid syndrome
• Type 1 or 2 DM
• Chronic hypertension
NICE Clinical Guideline; Hypertension in Pregnancy; August 2010 (revised reprint January
2011)
• Moderate risk (more than one of the following)
• First pregnancy
• Age 40 year-old
• Pregnancy interval of more than 10 years
• BMI of 35 or more at first visit
• Family history of pre-eclampsia
• Multiple pregnancy
NICE Clinical Guideline; Hypertension in Pregnancy; August 2010 (revised reprint January
2011)
ROLE OF CALCIUM
• To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes
• Randomised trials comparing at least 1 g daily of calcium during pregnancy with placebos
• Results
• 13 studies; 15730 women
• The average risk of high blood pressure was reduced with calcium supplementation (RR 0.65)
• Reduction in the average risk of pre-eclampsia associated with calcium (RR 0.45)
• Effect was greatest for women with low baseline calcium intake (RR 0.36) and those high risk
• Risk of preterm birth reduced (RR 0.76)
• Composite outcome maternal death or serious morbidity was reduced (RR 0.80)
• No overall effect on the risk of stillbirth or death
• Anomalous increase in the risk of HELLP syndrome (RR 2.67)
• Subgroup analysis showed no statistically significant effect of calcium on the incidence of pre-eclampsia in women with adequate dietary calcium
LIMITATION OF RECOMMENDATION
• Benefits are greatest in women with deficient dietary calcium
• Is it relevant to our population?
• Significance of the effect is influenced by pre-eclampsia risk status
• Greatest benefits for women who are high risk for pre-eclampsia
• Large studies were conducted in women at low risk and small trials were conducted in women at high risk
• Conclusion
• Although large studies on the use of calcium to prevent hypertensive disorders have been carried out, the variation in population and calcium status has made it impossible to reach a conclusion on the value of such treatment
OTHER INTERVENTIONS
• Not recommended
• Rest
• Low salt diet
• Exercise in pregnancy
• Weight management in pregnancy
• Other pharmaceutical agents (nitric oxide donors, progesterone, diuretics, LMWH)
• Nutritional supplements (Mg, Folic acid, antioxidants, garlic)
THANK YOUANY QUESTIONS?????