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Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

BMJ 2016; 353 doi: https://doi.org/10.1136/bmj.i1753 (Published 19 April 2016) Cite this as: BMJ 2016;353:i1753

Aspirin and Metformin for the prevention of Pre-eclampsia in obese pregnant women.

Aspirin and Metformin for the prevention of Pre-eclampsia in obese pregnant women.

Pre-eclampsia and eclampsia are serious or life threatening conditions that affects thousands of pregnant women and endanger them and their fetus. 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 (BMJ 2016; 353) identified 14 preeclampsia risk factors in 92 cohort studies comprising over 25 million pregnancies. The most prevalent in the studied population are pre pregnancy obesity (BMI over 30), and prior pre-eclampsia.

The rank of relative risk, the factors with the greatest risk for developing preeclampsia were: prior preeclampsia (RR, 8.4), chronic hypertension, pregestational diabetes, multifetal pregnancy, prepregnancy BMI above 30, and antiphospholipid antibody syndrome. Women who had antiphospholipid antibody syndrome had the highest preeclampsia rate (17%) although the lowest Population attributable fraction. Another observation by experienced clinicians is age less than 20 or over 35.

The authors conclude; Antiphospholipid antibody syndrome, prior pre-eclampsia, chronic hypertension, pregestational diabetes, assisted reproductive technology, and BMI >30 were most strongly associated with a high rate of pre-eclampsia, suggesting that the presence of any one might suffice to designate a woman as “high risk”. And 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 preeclampsia.

Werner EF et al (Obstet Gynecol 2015 Dec.) suggests 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 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 (N Engl J Med. 2016; 374:434-443), Syngelaki A, et al. 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 < .001), and in the incidence of preeclampsia (3.0% vs 11.3%, RRR 73%; P < .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, beside diet, to reduce the incidence of preeclampsia in obese pregnant women that could benefit many thousands of future mothers and their offspring.

Prof. Enrique Sánchez Delgado , MD

Internal Medicine-Clinical Pharmacology and Therapeutics

Juan J. Lugo Kautz, MD

Medical Chief, Gynecology-Obstetrics-Fertility Clinic

Hospital Metropolitano Vivian Pella, Managua.

Competing interests: No competing interests

30 April 2016
Enrique J. Sanchez-Delgado
Internal Medicine-Clinical Pharmacology and Therapeutics
Juan J. Lugo Kautz
Hospital Metropolitano Vivian Pellas
Managua, Nicaragua