Anxiety and Depression: Understanding the Risk for Preeclampsia

Hypertensive disorders of pregnancy (HDP) are comprised of 4 diseases: preeclampsia, gestational hypertension, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and eclampsia.¹ These diseases complicate approximately 5% to 10% of pregnancies.² Clinical guidelines differ on many aspects of the classifications of HDP but are consistent in describing these disorders as presenting on a continuum: women with untreated gestational hypertension may develop preeclampsia and untreated preeclampsia may manifest as HELLP syndrome or eclampsia.¹ A link between anxiety and depression and the risk for preeclampsia has recently been described n the literature, highlighting the need to screen pregnant persons for perinatal mood and anxiety disorders to improve patients’ mental health and possibly prevent preeclampsia.

Preeclampsia is defined as new-onset hypertension (systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg on at least 2 occasions ≥4 hours apart) at or after 20 weeks of pregnancy along with 1 or more of the following conditions: proteinuria, maternal organ dysfunction, and uteroplacental dysfunction. Maternal organ dysfunction is defined as renal (creatinine ≥1 mg/dL), neurologic (altered mental status, stroke, clonus), hepatic (elevated alanine aminotransferase >40 U/L with or without right upper quadrant/epigastric abdominal pain), or hematologic dysfunction (thrombocytopenia, disseminated intravascular coagulation, hemolysis).¹ Uteroplacental dysfunction includes fetal growth restriction and abnormal Doppler ultrasound of the umbilical artery.¹ Symptoms of HDP include hand and face swelling; headache; vision issues (blurred vision, photopsia, visual field defects, inability to focus, blindness); nausea and vomiting; and abdominal pain.^3,4

Hypertensive disorders of pregnancy can result in negative outcomes for both the mother and the newborn. Untreated preeclampsia, HELLP syndrome, and eclampsia often lead to premature delivery.⁵ According to the World Health Organization (WHO), complications of preterm birth are the leading cause of death among children younger than 5 years old. Those who survive may have learning disabilities and visual and hearing deficits.⁶ Hypertensive disorders of pregnancy can also cause maternal death.⁷ The Centers for Disease Control and Prevention (CDC) reports that HDP were responsible for 6.6% of pregnancy-related deaths in the US from 2014 to 2017.⁸ Pregnancy-related deaths increased in the US from 1987 to 2017,⁸ correlating with an increase in the rate of HDP from 528.9 per 10,000 deliveries in 1993 to 912.4 per 10,000 deliveries in 2014.⁹ Therefore, it is becoming increasingly important for health care clinicians to identify patients with risk factors associated with these disorders.

Potential Etiology

Although the cause of HDP is unknown, it is hypothesized that genetic, maternal/environmental, and immunologic factors may be associated with abnormal placentation that later leads to systemic vascular dysfunction.¹⁰

Symptoms of anxiety and depression during the perinatal period (during pregnancy and up to 1 year after birth) may be associated with an increased risk for HDP.¹¹ Perinatal mood and anxiety disorders (PMADs) affect approximately 1 in 5 women with anxiety and depression being the most common; other conditions include perinatal panic disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), bipolar disorder, and psychosis.¹² A retrospective study conducted by Raina et al that evaluated over 9 million pregnancies between 2004 and 2014, found that rates of mental disorders such as anxiety, bipolar disorder, depression, and mood disorders are increasing and are associated with an increased likelihood of HDP. After adjusting for sociodemographic characteristics and comorbidities, only anxiety was linked to an increased risk for gestational hypertension (adjusted odds ratio [aOR], 1.324; 95% CI, 1.255-1.397), preeclampsia (aOR, 1.522; 95% CI, 1.444-1.604), and eclampsia (aOR, 1.813; 95% CI 1.260-2.610).¹³

Stress, depression, and anxiety cause increased levels of corticotropin, which provokes cortisol release from the adrenal glands. High cortisol levels induce resistance to glucocorticoids by increased binding of cortisol to glucocorticoid receptors. This resistance in turn increases proinflammatory cytokines IL-1, IL-6, and tumor necrosis factor (TNF)-α, which can lead to systemic vascular dysfunction that precipitates glomerular endotheliosis and hypertension. Therefore, stress associated with diagnosis of preeclampsia may intensify psychological symptomatology.¹⁴

The COVID-19 pandemic led to a sharp increase in maternal anxiety rates.^15,16 This increase in anxiety is most likely related to maternal fear of infection for self and infant, social isolation, and uncertainty around COVID-19 spread.¹⁵ The unremitting nature of the pandemic is another factor that warrants consideration in research on the relationship between HDP and PMADs. The mental health repercussions of the COVID-19 pandemic emphasizes the need to provide a more detailed approach to evaluating mental health during pregnancy to prevent negative obstetric and neonatal outcomes. Over time, integrating this practice may reverse the rising rates of both disorders.

PMADs vs HDP: Which Comes First?

It is unclear whether PMADs precede HDP or vice versa. Findings from a population-based longitudinal study by Dachew et al showed that mothers with preeclampsia had a 53% increased risk for antenatal depressive symptoms.¹¹ Thombre et al found that prepregnancy depression or anxiety symptoms (ie, lifetime history or 1 year prior to pregnancy) were associated with an increased risk for HDP during pregnancy in a study of 1371 pregnant persons.¹⁷ Shay et al performed a meta-analysis of 61.2 million pregnancies in 2020 and found that when symptoms of anxiety or depression preceded diagnosis of hypertension, there was a statistically significant association between the conditions (relative risk, 1.27; 95% CI, 1.07-1.50).¹⁸ The authors concluded that women experiencing depression or anxiety in pregnancy had an increased prevalence of HDP compared to their nondepressed or nonanxious counterparts.

However, Mbarak et al found that depression onset followed preeclampsia diagnosis in 390 women in Tanzania; the authors concluded that 1 in 5 women with preeclampsia or eclampsia had postpartum depression.¹⁹ In 2019, Roberts et al found that women who experience HDP may be at an increased risk of developing postpartum depression, anxiety, and PTSD; however, it was unclear whether this association was caused by the hypertensive disorder, the impact of the disorder on the delivery/infant’s health, or if the psychological conditions were present prior to the pregnancy.²⁰

Thus, current studies suggest that pregnant persons can develop HDP before or after symptoms of depression and anxiety present. Clinicians should consider the relationship between HDP and PMADs when treating patients in their reproductive years; psychological status should be closely monitored before delivery and after delivery if complications occur.

Associated Risk Factors for Hypertensive Disorders of Pregnancy

In addition to PMADs, development of HDP may be associated with social and economic factors. Globally, studies have linked development of HDPs to violence, lack of prenatal assessments, unemployment, and lower levels of peer support.^21-24 Maternal physical health conditions associated with the development of HDP include chronic hypertension, pregestational diabetes, multiple gestations, prepregnancy body mass index (BMI) >30, antiphospholipid syndrome, and prior preeclampsia.¹⁰ Some of these risk factors, such as obesity and diabetes, are also associated with an increased risk for mood disorders.^25,26

Screening for Perinatal Mood and Anxiety Disorders

Evidence suggests that screening alone can help decrease symptoms of perinatal mental health disorders.²⁷ The American College of Obstetricians and Gynecologists (ACOG) recommends screening pregnant individuals for perinatal anxiety and depression at least once during the perinatal period using a standardized tool as well as during the comprehensive postpartum visit.²⁷ The US Preventive Services Task Force (USPSTF) also recommends screening perinatal and postpartum patients for depression but does not specify the optimal screening tool and frequency of administration.²⁸ The Alliance for Innovation on Maternal Health advises clinicians to obtain an individual and family history of mental health from all pregnant persons and screen for depression during pregnancy and in the postpartum period.²⁹ Postpartum Support International (PSI) endorses a more detailed timeline for screening: at the first prenatal visit, at least once in the second trimester, at least once in the third trimester, and at postpartum intervals with the woman’s primary care provider, obstetrician-gynecologist (ob-gyn), and infant’s pediatrician.³⁰

Most organizations do not specify which screening tool should be administered, as an optimal tool for screening perinatal anxiety is still being researched. Although the Edinburgh Postnatal Depression Scale (EPDS) is most commonly used for perinatal mental health screening,³¹ some evidence suggests that it does not sufficiently screen for anxiety because it is limited to 3 questions related to anxiety.²⁷ A study by Simpson et al that enrolled 240 perinatal patients referred for psychiatric consultation found that the General Anxiety Disorder-7 (GAD-7) had greater accuracy and specificity compared with the EPDS in diagnosing generalized anxiety disorder in this population.³²

Other factors to consider when determining the most effective screening tool are the number of questions and how long it will take to complete.²⁷ Other questionnaires to consider on a case-by-case basis for patients with PMADs other than anxiety and depression include the Yale-Brown Obsessive Compulsive Scale, Mood Disorder Questionnaire, and Impact of Events Scale-Revised. Further research is needed to determine the most effective screening methodologies and frequency.

This article originally appeared on Clinical Advisor

From the May/June 2022 Issue of Psychiatry Advisor