Faculty Bibliography

PURPOSE OF REVIEW:To synthesize and critically examine recent evidence regarding associations between immune system activity and perinatal depression. RECENT FINDINGS:Despite a significant number of studies assessing potential immunological markers of perinatal depression, it does not appear that levels of any individual pro- or anti-inflammatory marker is a useful predictor of perinatal depression. Some recent studies have observed differences in overall immune system functioning and adaptation across this period, taking into account multiple pro- and anti- inflammatory markers. Furthermore, there is evidence for interactions between depression and maternal psychosocial factors. Immune system functioning may be a mechanism through which social determinants of health contribute to risk for perinatal depression. There is substantial evidence implicating dysregulated immune activity in perinatal depression, yet little clarity regarding a consistent immune profile, especially based on analysis of circulating peripheral cytokines.

Human and animal neuroscience studies support the view that plastic shifts occur in the brain during pregnancy that support the emergence of new maternal behaviours. The idea of adaptive plasticity in pregnancy is at odds with the notion of "baby brain", in which pregnant women describe the onset of forgetfulness. While inconsistent evidence for memory deficits during pregnancy has been reported, few studies have investigated spatial associative memory (which is consistently enhanced in studies of pregnant rodents). Moreover, most studies assess domain-general stimuli, which might miss adaptations specific to parent-relevant stimuli. In the present study, we examined the retention of spatial associative memory for parenting-relevant and non-parenting-relevant stimuli across 4-weeks in a sample of women in their third trimester of pregnancy, and compared their performance to a sample of never pregnant women. We demonstrated that relative to never pregnant women, pregnant women exhibited enhanced long-term retention of object-scene-location associations (spatial associative memory), as well as better initial learning about parenting-relevant, relative to non-parenting-relevant, stimuli. Thus, similar to studies in rodents, cognitive improvements were seen during pregnancy in humans, and those improvements were specific to the domain of spatial associative retention, and in the recognition of stimuli relevant to parenting.

Inflammatory processes are a candidate mechanism by which early adversity may be biologically embedded and subsequently lead to poorer health outcomes; in pregnancy, this has been posited as a pathway for intergenerational transmission of adversity. Studies in non-pregnant adults suggest that factors such as mood, diet, BMI, and social support may moderate associations between childhood trauma history and inflammation in adulthood, though few studies have examined these associations among pregnant women. In a sample of healthy pregnant women (N = 187), we analyzed associations between maternal childhood adversity, including maltreatment and non-optimal caregiving experiences, with circulating Interleukin-6 (IL-6) levels during trimesters 2 (T2) and 3 (T3) of pregnancy. We also assessed whether these associations were moderated by psychosocial and lifestyle factors including depressive symptoms, social support, physical activity, and diet quality. History of childhood maltreatment was not associated with IL-6 in either T2 or T3 of pregnancy, either independently or in interaction with depressive symptom severity. However, in there was a significant positive association between childhood maltreatment and IL-6 in Trimester 2 in the context of poorer diet quality (p = 0.01), even after adjusting for BMI. Additionally, the quality of caregiving women received in childhood was associated with levels of IL-6 in Trimester 3, but only via interaction with concurrent depressive symptoms (p = 0.02). These findings provide evidence that for those with a history of childhood adversity, levels of inflammatory cytokines in pregnancy may be more sensitive to depressive symptoms and diet quality.

This chapter provides an overview of current research discoveries beginning to uncover the neurobiology of maternal mental illness. Results are described according to standard diagnostic categories (specifically, perinatal depression, perinatal anxiety and OCD, postpartum psychosis and bipolar disorder, and trauma and posttraumatic stress disorder), yet we aim to put this approach in context with the introduction of a classification model for psychiatric research, the research domain criteria, gaining traction in basic and clinical translational fields. We first review a new area of study, the neuroplasticity of the pregnant and postpartum brain, as work here has relevance for understanding the pathophysiology of mental disorders and may provide clues to changes in brain functioning that are related to compromised parenting in the context of postpartum depression. We next provide background information on neuroendocrine and immune changes during pregnancy and, to a lesser extent, the postpartum period, as alterations in these systems are significantly implicated in underlying neurobiology of mental illness for peripartum women. Our discussion of the major mental illnesses for pregnant and postpartum women includes neuroendocrine changes, neuroinflammation, and neurotransmitter alterations, as well as circuit dysfunction. Overall, remarkable progress has been made in identifying variations in neurobiology (and related systems) involved in maternal mental illness; yet, it is clear that, as classified with standard diagnostic systems, these are heterogeneous disorders and there is individual variability in the alterations in neurobiology for the same illness.

Maternal prenatal stress influences offspring neurodevelopment and birth outcomes including the ratio of males to females born; however, there is limited understanding of what types of stress matter, and for whom. Using a data-driven approach with 27 variables from questionnaires, ambulatory diaries, and physical assessments collected early in the singleton pregnancies of 187 women, 3 latent profiles of maternal prenatal stress emerged that were differentially associated with sex at birth, birth outcomes, and fetal neurodevelopment. Most women (66.8%) were in the healthy group (HG); 17.1% were in the psychologically stressed group (PSYG), evidencing clinically meaningful elevations in perceived stress, depression, and anxiety; and 16% were in the physically stressed group (PHSG) with relatively higher ambulatory blood pressure and increased caloric intake. The population normative male:female secondary sex ratio (105:100) was lower in the PSYG (2:3) and PHSG (4:9), and higher in the HG (23:18), consistent with research showing diminished male births in maternal stress contexts. PHSG versus HG infants were born 1.5 wk earlier (P < 0.05) with 22% compared to 5% born preterm. PHSG versus HG fetuses had decreased fetal heart rate-movement coupling (P < 0.05), which may indicate slower central nervous system development, and PSYG versus PHSG fetuses had more birth complications, consistent with previous findings among offspring of women with psychiatric illness. Social support most strongly differentiated the HG, PSYG, and PHSG groups, and higher social support was associated with increased odds of male versus female births. Stress phenotypes in pregnant women are associated with male vulnerability and poor fetal outcomes.

IMPORTANCE/UNASSIGNED:General trauma is the leading cause of nonobstetric maternal morbidity and mortality, affecting approximately 8% of all pregnancies. Pregnant women with traumatic brain injury (TBI) face high morbidity and mortality rates, requiring complex management due to physiological changes, teratogenic risks of treatments, and the need for fetal monitoring. OBJECTIVES/UNASSIGNED:To assess the consequences of TBI during pregnancy on maternal and fetal outcomes and to evaluate management strategies to inform clinical decision-making. EVIDENCE REVIEW/UNASSIGNED:A systematic literature search was conducted on January 12, 2024, in PubMed, Web of Science, and PsycInfo to identify articles published in English, German, or Spanish between January 1, 1990, and December 31, 2023, that included at least 1 pregnant individual with TBI. Peer-reviewed, human-based studies with original data on maternal and fetal outcomes were included. Reviews, meta-analyses, and nonhuman studies were excluded. Two independent reviewers screened abstracts and full-text articles. Study characteristics, pregnancy outcomes (maternal and fetal), management methods, and authors' conclusions were extracted. Risk of bias was assessed by 2 reviewers, with interrater agreement measured using Cohen κ. Disagreements were resolved through discussion. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed. FINDINGS/UNASSIGNED:This systematic review included 16 articles involving a total of 4112 individuals (mean maternal age, 26.9 years; range, 16-47 years) who experienced TBI during pregnancy (mean gestational age at injury, 24 weeks; range, 3-38 weeks). The articles comprised 10 case reports, 2 case series, and 4 cohort studies. Motor vehicle crashes were the most common cause of injury, reported in 12 articles. The average Glasgow Coma Scale score ranged from 3 to 15 across all individuals. Conservative management was reported in 7 case patients, whereas surgery was performed in 6 case patients. Maternal outcomes ranged from functional recovery to severe cognitive impairment, and fetal outcomes varied from stable to severe adverse outcomes, including stillbirth and death. Risk of bias assessment indicated moderate to good methodological validity overall, but most articles demonstrated poor quality of evidence. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this review, no definitive association between TBI during pregnancy and maternal or fetal outcomes was found owing to conflicting findings, poor to moderate study quality, and limited evidence. Although some articles suggested increased risks such as placental abruption and cesarean delivery, the findings remained inconclusive. The findings of this review underscore the need for high-quality research, standardized reporting, and rigorous methodology to improve data reliability. Future research should focus on developing consensus-driven, multidisciplinary management strategies to improve maternal and fetal outcomes.

INTRODUCTION/BACKGROUND:During the COVID-19 pandemic, birthing parents were identified as a high-risk group with greater vulnerability to the harms associated with SARS-CoV-2. This led to necessary changes in perinatal health policies but also to experiences of maternal isolation and loneliness, both in hospital settings, due to infection mitigation procedures, and once home, due to social distancing. METHODS:In this study, we qualitatively explored birthing and postpartum experiences in New York City during the early days of the pandemic when lockdowns were in effect and policies and practices were rapidly changing. Using thematic analysis, our focus was on experiences of isolation, navigating these experiences, and the potential impacts of isolation and loneliness on maternal health for 55 birthing people. RESULTS:Participants described numerous stressors related to isolation during the birthing process, including reconciling their hopes for their birth with the realities of the unknown and separation from partners, family, and friends in the hospital. During the postpartum period, loneliness manifested as having limited or no contact with family and friends, which led to feelings of a need for strengthened social support systems. The impact of these negative experiences shaped mental health. Overall, we found that solitary experiences during birthing and postpartum isolation were major sources of stress for participants in this study. DISCUSSION/CONCLUSIONS:To support impacted families and prepare for future crisis events, clinicians and researchers must prioritize the development of strong clinical and social support structures for perinatal people to ensure both maternal and child health.

BACKGROUND:Long-term deterioration in the mental health of healthcare workers (HCWs) has been reported during and after the COVID-19 pandemic. Determining the impact of COVID-19 incidence and mortality rates on the mental health of HCWs is essential to prepare for potential new pandemics. This study aimed to investigate the association of COVID-19 incidence and mortality rates with depressive symptoms over 2 years among HCWs in 20 countries during and after the COVID-19 pandemic. METHODS:This was a multi-country serial cross-sectional study using data from the first and second survey waves of the COVID-19 HEalth caRe wOrkErS (HEROES) global study. The HEROES study prospectively collected data from HCWs at various health facilities. The target population included HCWs with both clinical and non-clinical roles. In most countries, healthcare centers were recruited based on convenience sampling. As an independent variable, daily COVID-19 incidence and mortality rates were calculated using confirmed cases and deaths reported by Johns Hopkins University. These rates represent the average for the 7 days preceding the participants' response date. The primary outcome was depressive symptoms, assessed by the Patient Health Questionnaire-9. A multilevel linear mixed model (LMM) was conducted to investigate the association of depressive symptoms with the average incidence and mortality rates. RESULTS:A total of 32,223 responses from the participants who responded to all measures used in this study on either the first or second survey, and on both the first and second surveys in 20 countries were included in the analysis. The mean age was 40.1 (SD = 11.1), and 23,619 responses (73.3%) were from females. The 9323 responses (28.9%) were nurses and 9119 (28.3%) were physicians. LMM showed that the incidence rate was significantly and positively associated with depressive symptoms (coefficient = 0.008, standard error 0.003, p = 0.003). The mortality rate was significantly and positively associated with depressive symptoms (coefficient = 0.049, se = 0.020, p = 0.017). CONCLUSIONS:This is the first study to show an association between COVID-19 incidence and mortality rates with depressive symptoms among HCWs during the first 2 years of the outbreak in multiple countries. This study's findings indicate that additional mental health support for HCWs was needed when the COVID-19 incidence and mortality rates increase during and after the early phase of the pandemic, and these findings may apply to future pandemics. TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov, NCT04352634.