Is There a Relationship Between Prenatal Depression and Preeclampsia?

D epression is a recognized risk factor for the development of cardiovascular disease (CVD), which shares risk factors and patho-physiological features with preeclampsia.1,2 Thus, it is reasonable to hypothesize an association between the presence of mood disorder during gestation and preeclampsia. Potential mechanisms are similar to those hypothesized for depression and CVD, including chronic systemic and intravascular inflammatory processes, neuroendocrine, metabolic, and hypercoaguable disorders.3–5 Qiu and colleagues’ article in this issue provides some support for an association between depression and preeclampsia.6 Inclusive of this paper, there are six published studies of depression and preeclampsia, three of which report null findings, indicating that the current evidence remains inconclusive. A strength of the Qiu team’s study is that it uses data from the well-regarded Omega Study, an ongoing cohort study of risk factors for preeclampsia. They found that women with a depressive disorder diagnosed before conception or during the first 20 weeks of gestation had a 2.7-fold higher preeclampsia risk than those without a psychiatric diagnosis. Of note, women treated with selective serotonin reuptake inhibitors (SSRIs) had a lower relative risk of preeclampsia than the mood disorder group as a whole (1.81; 95% CI: 0.69– 4.75); relatively higher risks were observed among women prescribed with a combination of SSRIs and other medications (2.88; 95% CI: 0.40–20.98), and those treated exclusively with non-SSRIs (4.05; 95% CI: 1.26–13.02). The reduced risk associated with SSRI use suggests that serotonin regulation may be part of the common neuroendocrine pathway linking depression and preeclampsia. The authors note that their study is limited by small sample size—just nine women with preeclampsia had any reported mood or anxiety disorder, resulting in very wide confidence intervals. The authors did not use either a biomarker or a screening instrument to assess mood or anxiety disorders, instead relying solely on physician diagnosis as reported in the medical chart. Diagnoses alone may reflect differences in screening by providers or provider training in psychiatry. Although the authors argue that this method resulted in greater specificity and thus a conservative estimate of risk, it is also possible that variability in diagnostic approaches produced false positives as well as false negatives. Nonetheless, the very low prevalence reported in this sample (5.2%) is well below other estimates indicating that up to 18% of women are depressed during pregnancy.7 We look forward to more research about depression and preeclampsia. We recommend that future studies follow subjects throughout the course of pregnancy to detect new cases of depression, changes in severity, and treatment to facilitate assessment of temporal associations and dose response. New studies should incorporate additional measures, such as evaluation of biomarkers of depression (e.g., corticotrophinreleasing hormone (CRH) levels) along with a standard screening instrument. The Edinburgh Postnatal Depression Scale8 is commonly used to detect depression specific to pregnancy and it has been validated for use both during and after pregnancy.9 Concerns about overidentification can be addressed by assessing sensitivity and specificity and adjusting cutoff scores for the population to reduce false positives. Use of a multi-item screening instrument would also allow researchers to measure depression symptoms as a continuous variable to study dose response. Inclusion of biomarkers, such as serotonin, CRH, and pharmacological blood levels would help pinpoint the biological intersection between depression and preeclampsia. Epidemiologic study of modifiable risk factors for preeclampsia is important in order to stem maternal and infant morbidity. Although it is neither universal nor mandated, many prenatal care providers already screen patients for depression. Screening and diagnosis during early pregnancy not only provide an opportunity to treat depression, but diagnosis may give providers an early warning sign, alerting them to look for emergent signs and symptoms of gestational hypertension and preeclampsia.