2011 WHO Guidelines for Prevention and Treatment of

Pre-eclampsia and Eclampsia

J.P. Souza
Improving Maternal and Perinatal Health Unit, Department of Reproductive Health and Research, World Health Organization Geneva, Switzerland

Pre-eclampsia and Eclampsia

An important cause of severe morbidity, long term disability and death for mothers and babies Africa and Asia: about 10% of maternal deaths Latin America: main cause of maternal deaths Avoidable through timely and effective care Only definitive treatment is pregnancy termination or delivery

High Risk Populations

Previous pre-eclampsia Chronic hypertension Renal disease Diabetes Autoimmune disease Multiple pregnancies

http://www.who.int/publications/guidelines/en/

2011 WHO PE/E Guidelines

The guideline development methods included:
the identification of critical questions and critical outcomes the retrieval of the evidence (SR) the assessment and synthesis of evidence (GRADE) the formulation of recommendations & international consultation, and the dissemination, implementation, impact evaluation and continuous updating of the guideline.

Evidence Base
Calcium supplementation
13 RCTs, 15 730 women Dose used in the trials 1.5g 2.0g Risk of PE
All women: RR 0.45 (95%CI 0.31-0.65, 15730 women) High risk population: RR 0.22 (95%CI 0.12-0.42, 587 women) Low Ca intake: RR 0.36 (95%CI 0.20-0.65, 10676 women)

WHO Recommendation
In areas where dietary calcium intake is low, calcium supplementation during pregnancy (at doses of 1.52.0 g elemental calcium/day) is recommended for the prevention of pre-eclampsia in all women, but especially those at high risk of developing pre-eclampsia.

Evidence Base
Antiplatelet agents (aspirin)
60 RCTs, 37 720 women Particularly effective in high risk women:
RR 0.75, 95%CI 0.66-0.85, 18 trials, 4121 women

Aspirin initiation and gestational age

<20wks: RR 0.82 (95%CI 0.69-0.98) >20wks: RR 0.91 (95%CI 0.73-1.13)

WHO Recommendation
Low-dose acetylsalicylic acid (aspirin, 75 mg) is recommended for the prevention of pre-eclampsia in women at high risk of developing the condition. Low-dose acetylsalicylic acid (aspirin, 75 mg) for the prevention of preeclampsia and its related complications should be initiated before 20 weeks of pregnancy.

Evidence Base
Antihypertensive treatment
Multiple comparisons Low quality data Ongoing trials concerning moderate hypertension Hydralazine is the most studied drug for severe hypertension Ca channel blockers (e.g. nifedipine) good results

WHO Recommendation
Women with severe hypertension during pregnancy should receive treatment with antihypertensive drugs. The choice and route of administration of an antihypertensive drug for severe hypertension during pregnancy, in preference to others, should be based primarily on the prescribing clinician's experience with that particular drug, its cost and local availability hidralazine, nifedipine

Evidence Base
Magnesium sulfate for Eclampsia prevention Placebo comparison: Six trials (11 444 women), including the large Magpie trial (10 141 women) RR 0.41, 95%CI 0.29-0.58 No statistically significant differences were observed concerning respiratory arrest, respiratory arrest and use of Calcium gluconate.

Evidence Base
Magnesium sulfate for Eclampsia treatment 7 RCTs (1396 women); comparison: diazepam Death: RR 0.59, 95%CI 0.38-0.92 Recurrence of convulsions: RR 0.43, 95%CI 0.33-0.55

WHO Recommendation
Magnesium sulfate is recommended for the prevention of eclampsia in women with severe pre-eclampsia in preference to other anticonvulsants. Magnesium sulfate is recommended for the treatment of women with eclampsia in preference to other anticonvulsants.

WHO Recommendation
The full intravenous or intramuscular magnesium sulfate regimens are recommended for the prevention and treatment of eclampsia.
For settings where it is not possible to administer the full magnesium sulfate regimen, the use of magnesium sulfate loading dose followed by immediate transfer to a higher level health-care facility is recommended for women with severe pre-eclampsia and eclampsia.

Evidence Base
Induction of labour before term Sparse data, rare outcomes, small sample sizes, ethical constraints Interventionist approach: 24-48h stabilization (MgSO4, corticosteroids, antihypertensives) followed by delivery Expectant management: stabilization, monitoring and delayed delivery

WHO Recommendation
Induction of labour is recommended for women with severe preeclampsia at a gestational age when the fetus is not viable or unlikely to achieve viability within one or two weeks.

WHO Recommendation
In women with severe pre-eclampsia, a viable fetus and before 34 weeks of gestation, a policy of expectant management is recommended, provided that uncontrolled maternal hypertension, increasing maternal organ dysfunction or fetal distress are absent and can be monitored.

WHO Recommendation
In women with severe pre-eclampsia, a viable fetus and between 34 and 36 (plus 6 days) weeks of gestation, a policy of expectant management may be recommended, provided that uncontrolled maternal hypertension, increasing maternal organ dysfunction or fetal distress are absent and can be monitored.

Evidence Base
Induction of labour at term HYPITAT trial: 756 women with mild preeclampsia or gestational hypertension Reduced risk of severe hypertension among women receiving induction of labour
RR 0.60, 95%CI 0.38-0.95

Extrapolation to severe pre-eclampsia

WHO Recommendation
In women with severe pre-eclampsia at term, early delivery is recommended. In women with mild pre-eclampsia or mild gestational hypertension at term, induction of labour is recommended.

Evidence Base
Management of postpartum hypertension
Small sample sizes, rare events and moderate risk of bias Maximum incidence of severe hypertension at the end of the first week postpartum (when normally women are at the community) Higher incidence of stroke during postpartum Repercussions of mild (drug-induced) hypotension are relatively small, no fetal effects

WHO Recommendation
In women treated with antihypertensive drugs antenatally, continued antihypertensive treatment postpartum is recommended. Treatment with antihypertensive drugs is recommended for severe postpartum hypertension.

http://www.who.int/publications/guidelines/en/

WHO recommends against

Advice to rest at home for the primary prevention of pre-eclampsia Strict bedrest for improving outcomes of PE/E Restricted dietary salt intake Vitamin C,D,E supplementation Diuretics Corticosteroids for HELLP