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?????