Closer look at the cardiovascular and metabolic predictors of postpartum depression

Abstract

Postpartum depression (PPD) is a severe mental health disorder affecting 10% to 15% of postpartum women worldwide. Pre-eclampsia is a hypertensive disorder of pregnancy that has been identified as a significant factor for PPD due to its vascular dysfunction, systemic inflammation and neurobiological alterations. The neuroinflammatory mechanisms common to both pre-eclampsia and PPD, that contribute to depressive symptoms include elevated proinflammatory cytokines (interleukin-6, tumor necrosis factor-alpha), activation of the kynurenine pathway, and oxidative stress. To critically evaluate Wu et al's study, which investigates blood pressure variability (BPV) and gestational body mass index (BMI) as independent predictors of PPD. To integrate recent findings on the metabolic and cardiovascular links between depression, pre-eclampsia, and postpartum mental health outcomes. Pre-pregnancy BMI is found to be a stronger predictor of PPD than gestational weight gain. A vascular-neuropsychiatric connection has been indicated in pre-eclamptic women, indicating a significant correlation between BPV and depressive postpartum symptoms. There is increased susceptibility to depression due to neuroinflammation contributed by blood pressure fluctuations and metabolic dysregulation. The incidence of PPD could be reduced by early identification and intervention for BP fluctuations. Early detection and intervention in high-risk pregnancies should be conducted through public health strategies that prioritize awareness, education, and accessibility to mental health care.

Key Words: Postpartum depression; Pre-eclampsia; Blood pressure variability; Body mass index; Gestational weight gain; Maternal mental health; Inflammation and depression; Endothelial; Dysfunction; Neuroinflammation; Cardiovascular; Risk factors

Core Tip: A multidisciplinary approach in integrating mental health professionals and routine strategic care is essential for high-risk patients. Blood pressure variability (BPV) should be continuously monitored as fluctuations contribute to vascular dysfunction and worsening mental health outcomes. Additionally, excessive gestational weight gain alone does not significantly increase the risk of postpartum depression (PPD). Pre-pregnancy body mass index (BMI) is a more crucial factor. Therefore, BPV and pre-pregnancy BMI are the two most critical predictors of PPD in pre-eclamptic women.

TO THE EDITOR

Maternal well-being, infant development and family dynamics have been affected by postpartum depression (PPD), which is thus a major public health issue[1,2]. A well-documented risk factor for PPD, pre-eclampsia, is linked to vascular dysfunction, systemic inflammation and endothelial damage[3,4].

Sharing of pathophysiological mechanisms between pre-eclampsia and PPD, such as elevated pro-inflammatory cytokines [Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)], oxidative stress, and endothelial dysfunction contribute to depression pathogenesis[3,5]. Blood-brain barrier (BBB) permeability changes and kynurenine pathway activation are also involved[5].

Linking pre-eclampsia, body mass index and blood pressure variability

Pre-eclampsia is a complex pregnancy disorder characterized by systemic inflammation and hypertension, leading to endothelial damage and vascular dysfunction.

Vascular dysfunction and endothelial damage

Endothelial dysfunction in pre-eclampsia affects the endothelial health via oxidized toll-like receptors and low-density lipoprotein receptors, partly due to excessive hypercholesterolemia[6]. Pre-eclampsia increases the chance of cardiovascular risks in the long-term, as it is associated with systemic vascular dysfunction, which persists even after delivery[7,8]. Pre-eclampsia accelerates vascular aging due to increased expression of altered adhesion molecules and production of reactive oxygen species[9].

Systemic inflammation

Systemic inflammation is induced in pre-eclampsia by a marked increase in endothelial permeability and cytokine production[9]. This inflammatory response is exacerbated by high pre-pregnancy body mass index (BMI) by increased oxidative stress and adipose tissue inflammation[10].

Blood pressure variability

Blood pressure variability (BPV) contributes to endothelial damage and stress through reflection of instability in blood pressure regulation[8]. High BMI is linked further to vascular dysfunction as women with high BPV are more likely to have pre-existing obesity and hypertension[10].

Contradicting earlier results, Wu et al.’s studies[11] find pre-pregnancy BMI a stronger predictor than gestational weight gain (GWG) and BPV as risk factors in developing PPD[3].

As BPV is associated with vascular dysregulation that may exacerbate PPD symptoms, early intervention could mitigate both mental health and cardiovascular risks[4].

Gestational BMI and PPD

Inflammatory metabolic and psychological factors during pregnancy influence PPD. Recent evidence suggests that pre-pregnancy BMI is a stronger predictor than GWG alone[3].

Pre-pregnancy obesity vs excessive GWG (which matters more): One of the previous studies, particularly in Taiwanese women, suggested that emotional eating and excessive GWG had an association with increased PPD symptoms. It also challenged the previous assumptions by stating that pre-pregnancy BMI is a stronger predictor of PPD than GWG[12].

Studies that supported this notion include a meta-analysis study by Qiu et al[13], concluding both excessive and inadequate GWG increased PPD risk. In an analysis by Johar et al[14] (Germany), in women with a history of anxiety and depression, pre-pregnancy obesity was identified as the primary predictor of PPD, independent of GWG[14]. Another study by Adkins et al[15], in women with Class III obesity suggested that the effects of weight gain vary by severity of obesity, with no observed link between GWG and PPD[15].

Several mechanisms link pre-pregnancy obesity to PPD. Obesity is linked to pro-inflammatory cytokines (IL-6, TNF-α), serotonin disruption, and oxidative stress, causing chronic low-grade inflammation, collectively contributing to depression[3,16]. It also alters all cortisol levels and stress responses, disrupting the hypothalamic-pituitary-adrenal axis and increasing PPD risk[5]. Higher BMI correlates with psychosocial stress rooted in weight-related stigma and poor body image, which in turn contributes to PPD[17].

Therefore, for obese pregnant women, prioritizing pre-pregnancy weight counseling and routine mental health screening over GWG management alone could help identify high-risk patients and prevent PPD.

Contradictory evidence on BMI and PPD: The relationship between BMI and PPD is complex, with studies suggesting a U-shaped relationship where both high and low BMI are associated with increased depression risk[18]. As per research, individuals with both extremes of BMI (underweight and obese), show higher depression rates[18]. The point that appears slightly above the healthy BMI range is the turning point for increased depression risk.

Cultural and nutritional differences: Cultural factors, including societal norms about body image, with higher BMI being potentially stigmatized in some cultures, can influence depression risk[18]. As poor nutrition links to both depression and obesity, nutritional factors such as access to healthy foods and diet quality are also significant factors[18].

Genetic factors

Genetic predispositions may underlie both depression and higher BMI, with some individuals being genetically inclined to both[19].

Could higher BMI have a protective role: Though some studies suggest higher BMI may reduce antenatal depression risk, findings are mixed. A study by Zhou et al[20] (China, 4890 women) found that GWG increased the risk of anxiety, but there was no significant link between BMI and antenatal depression[20]. Another study by Chen et al[21] concluded that higher pre-pregnancy BMI did not affect PPD and was associated with a low risk of depression during pregnancy. Li et al[18] identified a U-shaped relationship between BMI and depression, indicating an increased risk at both extremely high and very low BMI levels[18].

Obese women possess protective mechanisms associated with higher BMI, which include neuroprotective effects on serotonin receptors resulting from elevated estrogen levels and a reduction in nutrient deficiency-related depression due to improved nutritional reserves[22].

These protective mechanisms have their limitations as obesity also contributes to the increased risk of pre-eclampsia, systemic inflammation, and metabolic dysfunction, which worsen mental health outcomes.

Psychological and behavioral interventions for weight-related PPD risk reduction: Behavioral and lifestyle interventions such as cognitive behavioral therapy for psychological distress and binge eating and Prenatal Exercise Programs that elevate the mood, reduce inflammation and lower PPD risk, can be inculcated[23,24].

Supplementing diet with omega-3 and probiotics can improve gut-brain communication and neuroinflammation, causing a potential reduction in PPD risk[5,25].

It should be encouraged for women with obesity or excessive GWG to undergo routine mental health screening and preconception weight management, focusing on metabolic health as a whole rather than weight gain alone.

BPV and mental health

The link between BPV and PPD: BPV is a marker of autonomic dysregulation and vascular dysfunction[26]. It is elevated in pre-eclampsia as it increases the risk of PPD[27,28]. Wu et al[12] found significant correlations between Edinburgh Postnatal Depression Scale (EPDS) scores and BPV (systolic and diastolic), strengthening the role of vascular instability in the onset of depression.

BPV categories

Ultra-short-term BPV: It is the beat-to-beat variation in BPV, driven by autonomic nervous system activity, vascular reactivity and heart rate variability[29,30]. It rejects immediate cardiovascular stress and regulatory mechanisms[29].

Short-term BPV: It is the variability measured by Ambulatory Blood Pressure Monitoring (ABPM) within 24 hours. It is strongly associated with cardiovascular events[30,31].

Mid-term BPV: It is the BPV over days to weeks, affected by lifestyle, environmental factors and medication adherence[30]. It contributes to chronic conditions like cognitive decline and renal failure.

Long-term BPV: It is the BPV over months to years, driven by arterial stiffness and vascular structural changes[29,30]. It predicts chances of mortality and adverse cardiovascular outcomes.

Individuals who have higher BPV carry a greater risk for cerebrovascular complications and cardiovascular diseases, leading to worsening mental health outcomes postpartum[32]. A systemic review by Shahimi et al[33] on individuals with psychiatric illnesses confirmed higher BPV to be the potential cause of increased target organ damage and cardiovascular complications. Modifiable psychosocial risk factors like workplace stressors have been associated with increased BPV, highlighting the role of external stress in mental and cardiovascular health[34]. A significant association of depressive mood with high visit-to-visit systolic BPV was found in a study on primary care patients by Lee et al[35], further corresponding to BP instability with mental health disorders.

Mechanisms connecting BPV and PPD: Pre-eclampsia contributes to oxidative stress, endothelial dysfunction and inflammatory cytokine release, which further leads to compromise of the integrity of the BBB[36]. It allows neurotoxicity substances to enter the brain and trigger neuroinflammation[37,38].

Pre-eclampsia plasma contains circulating anti-angiogenesis factors such as soluble fms-like tyrosine kinase (sFlt-1), which predisposes women to depression by increasing neuroinflammation and impairing cerebral perfusion[26]. Postpartum mood disorders are further worsened by oxidative stress and neural dysfunction carried out by pro-inflammatory cytokines (IL-6, TNF-α)[16].

BPV leads to autonomic dysregulation and neurovascular dysfunction that can heighten the stress response, worsen psychiatric symptoms and increase cortisol secretion[33]. It also contributes to an increasing risk of depressive episodes and emotional dysregulation[7].

Pre-eclamptic women are more likely to experience birth trauma and psychological stressors leading to PPD[3].

Clinical implications of BPV monitoring: There is a need to recognize BPV as an early biomarker for increased PPD risk in pre-eclamptic patients. Better risk assessment and intervention via ABPM, tracking real-time BPV[39]. BPV-related PPD risks can be mitigated through targeted interventions such as anti-hypertensive medications and lifestyle modifications[40]. Mental health screening in high-BPV pregnancies should be integrated as a part of routine care of obstetrics, especially in pre-eclamptic women having a high risk of developing PPD[41].

Clinical implications

Integrated prenatal care: Integrated prenatal care (IPC) is a comprehensive approach to maternity care that emphasizes collaboration among healthcare professionals to deliver seamless, women-centered care. The principles of IPC include: (1) Collaboration: Multidisciplinary teamwork across care levels[42]; (2) Woman-centeredness: Tailored care that focuses on the individual’s needs[42]; and (3) Continuity of care: Reduce fragmentation through coordinated services[42].

Implementation of specific interventions such as Mindfulness-Based Cognitive Therapy adapted for prenatal care[43], programs like the Women Adjusting to Various Emotional States (WAVES) protocol to support and educate those experiencing perinatal mental health issues[41], and use of mental health apps and telemedicine for continuous monitoring[44].

Evaluation criteria include outcome measures such as improved maternal-infant health and reduced PPD rates[41,42], as well as patient adherence and feedback rates to prenatal care protocols[45]. Therefore, an integrated approach can operationalize the recommendations.

Need for IPC: Mental health screenings are still not a part of routine prenatal care for hypertensive pregnancies despite growing evidence of it being a risk factor for PPD[41]. Higher rates of poor neonatal outcomes and emergency cesarean sections have been noted in hypertensive pregnancies due to failure to address mental health concerns[46]. Promising outcomes have been observed in the WAVES protocol, which integrates mental health into obstetric care, reducing maternal psychological distress[47]. Embedding behavioral health providers within perinatal care settings can help close the gap in mental health care access and early intervention[48].

Weight and BPV management in pregnancy: Inadequate weight gain leads to fetal growth restriction, whereas excessive GWG increases the risk of gestational diabetes, emergency deliveries and hypertension[49]. It is crucial in pre-eclamptic women to manage weight and BPV as it lowers the risk of adverse birth outcomes and maternal morbidity[24]. Interventions such as physics, activity programs and structured diets have proven effective in reducing hypertensive complications and preventing excessive GWG[50]. In marginalized communities, addressing ethnic and racial disparities in maternal care access is crucial to improve outcomes[51]. Telehealth systems allow real-time monitoring and interventions, proving to be an effective tool for weight management in pregnancy[52].

Future research directions

Long-term impact of pre-pregnancy BMI and BPV on PPD: PPD rates have shown an increase across all BMI categories, with obese individuals having the highest risk[53]. The need for continuous BP monitoring during pregnancy has been emphasized, as it has been demonstrated to predict lower postpartum psychological distress[54]. Unfortunately, there is a lack of longitudinal studies that assess the impact of BMI and BPV stabilization on long-term maternal mental health outcomes[55].

Cardiovascular risk markers: Key markers like endothelial dysfunction, arterial stiffness and early vascular aging, have long-term implications for mental and cardiovascular health.

Endothelial dysfunction: It is characterized by increased vasoconstrictor activity and reduced nitric oxide availability, which plays a central role in thrombosis and atherogenesis[56].

Arterial stiffness: It is measured by pulse wave velocity and augmentation index, and is a predictor of cardiovascular events. It reflects the cumulative vascular damage[57,58].

Early vascular aging: It indicates the accelerated vascular aging due to risk factors such as obesity and hypertension, which contributes to higher long-term cardiovascular risk[58,59]. The long-term implications include increased risks of stroke, myocardial infarction, cognitive decline and overall mortality[56,60].

Cardiovascular risk markers in pre-eclamptic women

Women with a previous history of pre-eclampsia are at a higher risk of hypertension, metabolic syndrome and insulin resistance postpartum[61]. A significant concern in pre-eclamptic women is early vascular aging, found in an early vascular aging study, increasing their risk of cardiovascular diseases[59]. The P4 study suggested an ongoing cardiovascular risk, demonstrating that pre-eclamptic women had significant arterial stiffness and higher blood pressure 2 years postpartum[61]. Effectiveness in promoting healthier behaviors and improving cardiovascular outcomes in pre-eclamptic patients has been seen in postpartum vascular risk reduction clinics[40].

Socioeconomic and racial influences

Socioeconomic and racial factors significantly influence maternal health outcomes. Socioeconomic status has been recognized as a key determinant of maternal health outcomes, including education, income and employment, affecting healthy lifestyle choices and access to healthcare[62-64]. Access to healthcare, economic constraints, and physical environment are also contributing factors in long-term maternal mental and cardiovascular health outcomes[65].

Racial disparities, especially in Black mothers, have a significant impact on PPD and hypertensive disorders due to social determinants of health[66]. Hispanic and Non-Hispanic Black often exhibit higher rates of obesity and hypertension due to systemic barriers, which exacerbate BMI and BPV-take risks[67]. Therefore, a need for a comprehensive intervention policy addressing education and healthcare access for low-income and minority groups is crucial for improving maternal mental health outcomes[68].

Long-term follow-up

Long-term longitudinal studies are critical for understanding how changes in BPV and BMI influence postpartum mental health over time. Such studies should evaluate the efficacy of interventions such as integrative health promotion strategies and home visiting programs[69,70], regularly track BPV and BMI using standardized tools like the Patient Health Questionnaire and EPDS[71], and consider external factors such as healthcare access and socioeconomic status in their analysis[62].

CONCLUSION

To conclude, in pre-eclamptic women, BPV and pre-pregnancy BMI are significant predictors of PPD risk. Prioritizing maternal weight management and BPV monitoring should be included in routine prenatal care. The long-term mental health and cardiovascular implications of pre-eclampsia and hypertensive pregnancies should be an investigatory topic in future research.