A meta-analysis of 92 studies has identified six risk factors for pregnancy-related hypertension (preeclampsia) — prior preeclampsia, diabetes prior to conception, prolonged hypertension, antiphospholipid antibody syndrome, BMI >30, and assisted reproductive technology. The findings were published in British Medical Journal. The study also generated the absolute risk of developing preeclampsia on the basis of presence or absence of these risk factors.

Pre-eclampsia, or pregnancy-related hypertension, is a condition that affects some pregnant women either in the second trimester or soon after delivery. There are several risk factors that can help identify women at high-risk of developing preeclampsia. However, a clear, concise and definitive list of these clinical indicators is lacking. A majority of the clinical trials studying preeclampsia in pregnant women have not described the criteria to define women at high-risk of developing the common pregnancy-related condition. While others relied on the abnormal findings of the diagnostic modalities, such as uterine artery Doppler ultrasonography, to characterize the risk, yet some other studies proposed a number of risk factors to identity women at high-risk, such as prepregnancy diabetes mellitus, chronic hypertension, advanced maternal age and nulliparity.

However, clear indicators, encompassing events and risks of past pregnancy and those of current pregnancy, have never been identified. The current meta-analysis conducted by a team of medical students, epidemiologists and a clinical scientist attempted to bridge the gap. It has generated three practical estimates:

  1. Absolute risk of preeclampsia development in the presence or absence of a risk factor
  2. Relative risk of preeclampsia development in the presence or absence of a risk factor
  3. Percentage of population attributable in relation to each risk factor

The first two metrics have a clinical value and usefulness, while the third can have applications in designing the public health policy.

Systemetic Review And Meta-Analysis

The systematic review and meta-analysis, in question, comprised analyzing studies and trials conducted from 2000 to 2015. The meta-analysis studied a total of 25,356,688 pregnancies from 92 cohort studies carried out in 27 countries, and kept a record of risk-factors from earlier pregnancies (preeclampsia, fetal intrauterine growth restriction, placental abruption, and stillbirth), and current pregnancy. The risk-factors of the current pregnancy included old age, nulliparity, raised BMI, assisted reproduction (IVF), antiphospholipid antibody syndrome, chronic hypertension, prepregnancy diabetes mellitus, chronic kidney disease, systemic lupus erythematosus, and multiparity.

Of the 92 studies, 55 were retrospective and 37 were prospective. Of 100% pregnancies, 62% (n=57) involved singleton pregnancies. It was noted that the incidence of antiphospholipid antibody syndrome was ranked first on pooled event rate of preeclampsia (17.3%); the prior preeclampsia, second. Chronic hypertension had the second highest pooled rate (16.0%) and pooled relative risk (5.1) of pre-eclampsia.

On the population attributable fraction, nulliparity showed the highest incidence for preeclampsia (32.3%). Pre-pregnancy hypertension was ranked second (23.8%), followed closely by BMI >25 (22.0% – 25.6%) and prior preeclampsia (22.8%). Antiphospholipid antibody was ranked lowest on the population attributable fractions (0.18%).

As for the use of aspirin to prevent the incidence of preeclampsia in pregnant women, different risk factors (as listed above) showed an individual threshold number.

Strengths And Limitations Of The Analysis

The meta-analysis involved studying data obtained from more than 25 million women from across the world, making it a widely acceptable review. Moreover, the risk factors studied were largely accepted by most of the clinicians. A selection of only large cohort studies helped reduce the risk of bias commonly associated with small studies.

As for the limitations of the meta-analysis, 15 out of 92 studies selected for the review lacked a definitive definition of preeclampsia. An inconsistency in the definition of several risk factors was also noticed, such as “renal disease” was considered any loss of kidney functions ranging from mild to severe. Such variations in definitions can cause heterogenecity in the risk estimates.

Furthermore, the analysis could not identify the interactions between the risk factors.

Result And Discussion

Based on the findings of large sample cohort studies, the researchers identified the following risk factors for the development of pre-eclampsia in pregnant women: prior preeclampsia, diabetes prior to conception, prolonged hypertension, antiphospholipid antibody syndrome, and BMI>30. The identification was based on the absolute rate and relative risk of preeclampsia as well as on the population attribution fraction.

The meta-analysis concluded that the quantification of the risk of preeclampsia can better equip a clinician to identify a woman at a heightened risk of the complication, and to provide appropriate prophylactic measures, such as aspirin. The population-attribution fractions, as highlighted by the meta-analysis, can also help to modify the risk factors associated with the gestational complication. For example, pre-pregnancy obesity is closely linked with hypertension, reducing pre-pregnancy BMI can help to lower BP in such women. As for non-modifiable risks, alternative therapeutic strategies can be opted to lower the risk of preeclampsia, for example, prophylactic use of aspirin in women with a history of preeclampsia. Other risk factors that can be effectively avoided with a prophylactic use of aspirin include prior preeclampsia, diabetes prior to conception, prolonged hypertension, antiphospholipid antibody syndrome, BMI>30, and assisted reproductive technology. To identify these risk factors, the meta-analysis opted for a conservative approach in setting the low threshold number (NNPT = 250).

The meta-analysis identified six risk factors associated strongly with the possible development of preeclampsia. These include: prior preeclampsia, diabetes prior to conception, prolonged hypertension, antiphospholipid antibody syndrome, BMI>30, and assisted reproductive technology.

The role of prior intrauterine growth as a risk factor for preeclampsia remains to be defined since it is a heterogenous state itself and requires a standard definition.

The findings of the meta-analysis warrant an evaluation with a multivariable model using a combination of various risk factors to examine the risk of preeclampsia.

Additionally, the analysis suggests further evaluation to determine the efficacy of aspirin in the prophylaxis of preeclampsia.

About The Risk Of Preeclampsia

Preeclampsia, accounting for 5-8% of all births in the United States, is a pregnancy-related complication that is characterized by hypertension and a presence of protein in the urine (called proteinuria). Each year, about 10 million women develop pre-eclampsia. Globally, preeclampsia accounts for 76,000 deaths. The number of babies dying per year from preeclampsia and related hypertensive disorders is around 500,000.

Antiplatelet agents, such as aspirin, are an effective and safe therapy to prevent preeclampsia in women at moderate-to-high-risk of developing preeclampsia.