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Date of release: 11 July, 2016

Prevention of pre-eclampsia: potential of proven drugs

Pre-eclampsia and eclampsia are serious or life-threatening conditions that affect thousands of pregnant women and endanger them and their fetuses. It is fundamental to know the main risk factors to prevent this disease with the safest and most cost-effective approaches. The High Risk of Pre-eclampsia Identification Group [1] identified 14 pre-eclampsia risk factors in 92 cohort studies comprising over 25 million pregnancies. The most prevalent in the studied population are pre-pregnancy obesity (body mass index (BMI) over 30 kg/m2), and prior pre-eclampsia. The factors with the greatest risk for developing pre-eclampsia were: prior pre-eclampsia (relative risk (RR) 8.4), chronic hypertension, pregestational diabetes, multifetal pregnancy, prepregnancy BMI > 30 kg/m2, and antiphospholipid antibody syndrome. Women who had antiphospholipid antibody syndrome had the highest pre-eclampsia rate (17%), although the lowest population attributable fraction.

The authors concluded that antiphospholipid antibody syndrome, prior pre-eclampsia, chronic hypertension, pregestational diabetes, assisted reproductive technology, and BMI > 30 kg/m2 were most strongly associated with a high rate of pre-eclampsia, suggesting that the presence of any one factor might suffice to designate a woman as at 'high risk'. They recommend starting treatment with aspirin at 12–16 weeks’ gestation in these women at high risk of pre-eclampsia, calculating a number needed to treat (NNT) of less than 250 to prevent a case of pre-eclampsia.

Comment

Werner and colleagues [2] suggest that broadening the use of low-dose aspirin prophylaxis to all women at moderate and high risk for pre-eclampsia has significant public health benefits. In moderate-risk and high-risk women, aspirin prophylaxis versus no treatment modestly lowers the risk for pre-eclampsia (9.5% vs. 11.4%, relative risk reduction or RRR 17%, NNT 53), preterm birth (21.7% vs. 24.4%, RRR 11%, NNT 37), and fetal growth restriction (7.7% vs. 8.6%, RRR 10%, NNT 111).

In another related interesting study, Syngelaki and colleagues [3] used metformin (a safe and proven drug for diabetic pregnant women) in a dose of 3.0 g per day in obese pregnant women without diabetes mellitus. There were 225 women in each group. The treated women benefited in the median maternal gestational weight gain (4.6 vs. 6.3 kg; p < 0.001), and in the incidence of pre-eclampsia (3.0% vs. 11.3%, RRR 73%; p < 0.001. Potential NNT 12), both of which were lower in the metformin group in comparison to placebo.

These studies suggest the potential benefit of using aspirin and metformin, besides diet, to reduce the incidence of pre-eclampsia in obese pregnant women and this could benefit many thousands of future mothers and their offspring.

Enrique Sánchez Delgado


Internal Medicine-Clinical Pharmacology and Therapeutics



Juan J. Lugo Kautz


Medical Chief, Gynecology-Obstetrics-Fertility Clinic, Hospital Metropolitano Vivian Pella, Managua



    References

  1. Bartsch E, Medcalf KE, Park AL, Ray JG; High Risk of Pre-eclampsia Identification Group. Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies. BMJ 2016;353:i1753


    http://www.ncbi.nlm.nih.gov/pubmed/27094586

  2. Werner EF, Hauspurg AK, Rouse DJ. A cost-benefit analysis of low-dose aspirin prophylaxis for the prevention of preeclampsia in the United States. Obstet Gynecol 2015;126:1242-50


    http://www.ncbi.nlm.nih.gov/pubmed/26551178

  3. Syngelaki A, Nicolaides KH, Balani J, et al. Metformin versus placebo in obese pregnant women without diabetes mellitus. N Engl J Med 2016;374:434-43


    http://www.ncbi.nlm.nih.gov/pubmed/26840133