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Prevention of pre-eclampsia

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Prevention of Pre-eclampsia

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Prevention of pre-eclampsia

  1. 1. PREVENTION OF PREECLAMPSIA ROLE OF ASPIRIN AND CALCIUM Dr Kanddy O&G Updates Miri Hospital 1/11/14
  2. 2. DEFINITIONS • Chronic hypertension • Hypertension (BP ≫ 140 90 mmHg; 4 – 6 hours apart); < 20 weeks of gestation • Gestational hypertension • Hypertension (BP ≫ 140 90 mmHg; 4 – 6 hours apart); > 20 weeks of gestation • Without significant proteinuria • Pre – eclampsia • Hypertension (BP ≫ 140 90 mmHg; 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
  3. 3. • Eclampsia • Seizure associated with pre-eclampsia • Chronic hypertension with superimposed pre-eclampsia • Unclassified hypertension • Hypertension (BP ≫ 140 90 mmHg; 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)
  4. 4. PATHOPHYSIOLOGY • Unknown
  5. 5. BURDEN OF PRE-ECLAMPSIA • One of the major cause of maternal mortality
  6. 6. MATERNAL MORTALITY - MALAYSIA
  7. 7. • 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
  8. 8. REDUCING THE RISK OF HYPERTENSIVE DISORDERS IN PREGNANCY • Pre-existing risk factors • Modifiable • Obesity • Non-modifiable • Medical illnesses • Age • Primiparity • Family history
  9. 9. 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
  10. 10. CLASP TRIAL
  11. 11. • 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)
  12. 12. • 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
  13. 13. • 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.
  14. 14. • 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.
  15. 15. 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)
  16. 16. • 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)
  17. 17. ROLE OF CALCIUM
  18. 18. • 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)
  19. 19. • 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
  20. 20. 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
  21. 21. 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)
  22. 22. THANK YOU ANY QUESTIONS?????

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