Despite several decades of extensive research into its pathogenesis, preeclampsia continues to be a syndrome of unknown etiology.
Several theories on the mechanisms leading to preeclampsia have been proposed, all based on numerous pathophysiological abnormalities reported in association with the heterogeneous disorder.
These theories, which have been developed largely during the past 2 decades, involve abnormalities such as impaired trophoblast differentiation and invasion, placental and endothelial dysfunction, immune maladaptation to paternal antigens, an exaggerated systemic inflammatory response, and a state of imbalance between proangiogenic and antiangiogenic factors.
As evidence for these theories has unfolded, investigators have identified numerous risk factors for preeclampsia. Most of them are preexisting risk factors that can be identified either before a patient becomes pregnant or early in the pregnancy. (See box below.)
The disorder's pathogenesis can vary in women with different risk factors or different times of onset. In women with previous preeclampsia, for example, the risk for developing recurrent preeclampsia varies depending on the underlying mechanism and the outcome in the previous pregnancy.
What this means is that even as investigators work to improve our understanding of the disorder, we as clinicians have an immediate opportunity—and responsibility—to identify patients who are at risk for preeclampsia, or recurrent preeclampsia, during preconception counseling or early in gestation.
We can then work with at-risk patients to optimize their health before conception and to carefully manage maternal and fetal well-being during pregnancy.
Women with a history of previous preeclampsia—even those who suffered serious adverse outcomes—should be counseled about their risks and reassured about our ability to optimize outcomes through vigilant monitoring, early detection of complications, and timely delivery.
And in an effort to improve their long-term health, these women should also be counseled about an increased risk for cardiovascular disease and ischemic stroke later in their lives.
A healthy 22-year-old woman with an ideal body weight and no preexisting medical risk factors who plans to become pregnant for the first time.
This patient's risk for preeclampsia is low (only 1%-2%). If preeclampsia occurs, it is likely to be mild, with an onset near term or intrapartum, and with generally good outcomes.
Nevertheless, it is important to inquire about any family history of preeclampsia or cardiovascular disease in this type of patient, and to be aware that women who themselves were born small for gestational age have an increased risk for preeclampsia, as does any woman whose husband or partner fathered a preeclamptic pregnancy in another woman.
Certain changes and events can also occur during pregnancy that will increase her risk. If, during antenatal care, ultrasound reveals multifetal gestation or unexplained fetal growth restriction, for instance, her risk of preeclampsia will increase substantially. (See box, page 9, top right.)
Likewise, if she develops gestational hypertension, her risk will increase to 25%-50% based on gestational age at the time the hypertension developed.
Several recently published studies have reported an association between maternal infections and an increased risk of preeclampsia as well. (Infections probably increase a maternal inflammatory response that already is engendered by the pregnancy itself.)
A systematic review published in 2006 found that the odds ratio for preeclampsia was 1.57 in women with urinary tract infections, and 1.76 in women with periodontal disease (N. Engl. J. Med. 2006;355:992-1005).
Unfortunately, the various biomarkers that have been proposed to predict which women are likely to develop preeclampsia—from serum placental growth factor to asymmetric dimethylarginine—have not been shown to be reliable and are not predictive or specific enough for use in clinical practice.
Likewise, supplementation with fish oil, vitamin E, vitamin C, low-dose aspirin, or calcium is not recommended for the prevention of preeclampsia in the young woman with no risk factors.
A 42-year-old who is trying to become pregnant for the first time.
This patient's older age is itself a risk factor for preeclampsia. An older age also often means more body weight and a higher likelihood of chronic hypertension or diabetes, as well as an increased likelihood that donated gametes were used, all of which can significantly increase risk.
As in the case of the younger patient, risk evaluation and management should begin before conception. Family history, personal birth history, and the history of the patient's husband or partner should be explored.
And because a high body mass index is a proven risk factor—as is insulin resistance, which is often linked with obesity—patients who are overweight or obese should be encouraged to lose weight and achieve a healthy BMI.
The risks associated with preexisting medical conditions like hypertension and diabetes vary depending on the conditions' severity.