This document discusses strategies for preventing preeclampsia, including the roles of aspirin and calcium supplementation. It summarizes several studies that have examined the effects of these interventions. The studies found that aspirin reduces the risk of preeclampsia by 17% and the risk of preterm birth by 8%. Calcium supplementation, especially for those with low dietary calcium intake, reduces the risk of preeclampsia by 45% and the risk of preterm birth by 24%. However, the benefits of calcium may depend on preeclampsia risk factors and dietary intake. The document concludes that aspirin and calcium supplementation can help reduce risks, but their effects may vary depending on individual risk profiles.

1. PREVENTION OF
PREECLAMPSIA
ROLE OF ASPIRIN AND CALCIUM
Dr Kanddy
O&G Updates
Miri Hospital
1/11/14

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. • 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. PATHOPHYSIOLOGY
• Unknown

6. BURDEN OF PRE-ECLAMPSIA
• One of the major cause of
maternal mortality

7. MATERNAL MORTALITY - MALAYSIA

8. • 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

9. REDUCING THE RISK OF HYPERTENSIVE
DISORDERS IN PREGNANCY
• Pre-existing risk factors
• Modifiable
• Obesity
• Non-modifiable
• Medical illnesses
• Age
• Primiparity
• Family history

10. 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

11. CLASP TRIAL

12. • 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)

13. • 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

15. • 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.

16. • 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.

17. 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)

18. • 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)

19. ROLE OF CALCIUM

20. • 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)

21. • 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

22. 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

23. 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)

24. THANK YOU
ANY QUESTIONS?????