Neda Razaz

Research problem:  In Sweden, around 9,000 women with pre-existing psychiatric disorders give birth annually, with rates increasing. Severe perinatal psychiatric disorders (SPPD)—including acute psychosis and suicide during pregnancy and up to one year postpartum—are among the leading causes of maternal mortality. Despite growing awareness, key gaps remain in identifying high-risk groups, understanding paternal mental health, and assessing long-term impacts on families.Overall aim: This project aims to investigate risk factors for SPPD in both women and men and to evaluate its long-term consequences for family health. Using linked population-based cohorts from Sweden and British Columbia, we will follow approximately 3.5 million individuals (2000–2024). Specific objectives:Aim 1: Determine the prevalence, incidence and risk factors for SPPD in mothers and fathers during pregnancy and first year postpartum, inlcuding socioeconomic status (i.e., rural/urban area and obstetric complications.Aim 2: Evaluate the association between SPPD and long-term health and economical outcomes for women, men, and offspringAim 3: Use causal inference methods (sibling comparisons, paternal SPPD as negative control) to disentangle genetic and environmental influences.Impact: Findings will guide prevention, early detection, and targeted support to reduce psychiatric morbidity and improve family well-being.

Research problem Annually, more than 3500 women in Sweden (~3%) experience severe, unexpected illness during pregnancy. Severe maternal morbidity refers to unexpected complications during pregnancy, childbirth, and postpartum. Cardiovascular and pulmonary contributions to severe maternal morbidity (CPSMM) including cardiac arrest, arrhythmia, pulmonary embolism and acute myocardial infarction are on the rise. This increase is probably driven by changing demographics of the pregnant population including more women of extreme maternal age and an increased prevalence of cardiometabolic and structural heart disease. Beyond physical implications, these conditions often profoundly impact women s mental, functional, and social wellbeing. However, data on the long-term effects of CPSMM remain sparse or non-existent. Aim: This project aims to address this knowledge gap by comprehensively assessing the neglected long-term impact of cardiovascular and pulmonary severe maternal morbidity (CPSMM) on diverse aspects of women s health over two-decades, following pregnancies complicated by CPSMM. Our specific objectives are: to evaluate the impact of both overall and specific CPSMM subtypes on long-term: o reproductive health (e.g., likelihood of subsequent birth, recurrent CPSMM)

o physical and mental health (e.g., mortality, and psychiatric disorders)

o labour-market productivity (e.g., disability pension and wage loss). Utilize sibling-controlled analyses to account for shared familial confounding among sisters. Plan for project realisation: Utilizing two population-based cohorts, we will analyse data sources from Sweden and British Columbia (BC), Canada, and follow ~3.0 million women for up to 22 years

from 2000-2022. Data access and linkage from 2000 to 2019 are established in both regions, with ongoing updates to extend cohorts to 2022. Relevance: CPSMM is rising and has become the leading cause of maternal mortality, however our understanding of its long-term effects is limited. This longitudinal study is the first population-based study addressing a crucial gap by examining the long-term burden of diverse CPSMM complications, globally affecting millions of women annually. The perinatal and postpartum periods are opportune times to intervene since virtually all pregnant and delivering women are already well-connected with the health care system for obstetric care. Improving pregnancy health cannot be achieved without improving women s health.

Neonatal mortality has declined substantially during the last decades, especially in infants born preterm, which is primarily due to the highly specialized care provided in neonatal intensive care units (NICU). In Canada, 8% of infants are born preterm and up to 10% of babies are admitted to NICU. Surviving preterm infants face higher risk of neurodevelopmental disorders later in life, and these risks increase with decreasing gestational age at birth. The purpose of this project is to employ cutting edge epidemiological approaches in the analyses of uniquely rich population data sources available in British Columbia (BC), Canada, and Sweden. This project aims to fill the knowledge gaps regarding babies' risk factors associated with increased morbidity, including the reasons for preterm delivery and postnatal interventions, which influence neurodevelopmental disorders in childhood and early adulthood. Most previous studies were hospital-based and included a relatively small number of infants that were followed up throughout the childhood and adolescence. We propose to create a virtual cohort of approximately 3.7 million singleton infants with a follow-up of up to 22 years. We will use artificial intelligence (machine learning techniques) to create prediction models that will identify individual risk factors that place preterm infants at higher risk of death or illness later in life. We will also use special analytical designs to investigate differences between boys and girls and between siblings. These results will be compared between two high-income countries with different preterm birth rates, Canada (8.3%) and Sweden (5.6%). The between-country comparisons will help us study how various causes of preterm birth affect long-term prognosis. We anticipate that this will be the largest population-based study to date to provide a robust evidence about the effects of newborn conditions on health and developmental trajectories of children and adolescents born preterm.

Background: Multiple sclerosis (MS) predominantly affects women, and the clinical onset of MS often occurs during child-bearing age. Clinicians recommend discontinuation of disease-modifying therapies (DMTs) before conception unless the risk of disease worsening outweighs the risk to the fetus. New high-efficacy DMTs such as rituximab, a chimeric monoclonal B-cell-depleting anti-CD20 antibody, are frequently used off-label for the treatment of MS in Sweden. Objective: There is a lack of evidence on the influence of DMTs including anti-CD20-antibodies on the infant´s immune system and their responses to vaccination during the first months after birth. Purpose: To fill the knowledge gaps regarding the impact of the mother´s DMT on a newborn´s humoral immune system. Aims: To investigate the association between mother´s exposure to DMTs pre-pregnancy and infant´s 1) successful B-cell production 2) vaccine response and 3) risk of infections within the first year. Setting: a) Retrospective cohort study with infants born between 2012 and 2022 to mothers with MS treated with DMTs. The infants´humoral immune system will be assessed by analyzing markers of successful B-cell production in newborn dried-blood spot samples. b) Prospective cohort study, recruiting between 2024 och 2025. Vaccine responses and infection rates in infants to mothers with rituximab will be compared to mothers with other DMTs prior to pregnancy.

Background: Preeclampsia (PE), a severe hypertensive disorder affecting about 5% of all primiparous pregnancies, is strongly associated with complications in subsequent pregnancies and early-onset of cardiovascular diseases (CVD) as myocardial infarction and stroke. Traditional CVD risk factors arising after pregnancy are strongly associated with the increased CVD risk in women with previous PE, with pregnancy weight retention and overweight/obesity being key modifiable factors. Thus, the first postpartum phase provides a window of opportunity for screening and implementing preventive interventions. Given this, there is a high clinical need for evidence-based postpartum interventions that can mitigate the risk of future overweight/obesity and to improve the cardiometabolic profile, to potentially delay or prevent future CVD. Objectives: The overall aim is to address the lack of evidence to improve cardiometabolic health in women with previous PE. With a multidisciplinary team including representatives from the PE Patient Organisation and informed by a feasibility study, we will evaluate the efficacy of a clinically implementable bundle intervention program tailored for postpartum women with PE in first pregnancy. Our hypothesis is that the intervention will be feasible with high compliance, and effective in reducing postpartum maternal BMI and improve cardiometabolic profile 1 year after birth. Work plan: We will conduct a multi-centre two-armed single-blind parallel randomised controlled trial of 700 participants (350 in each arm), between 3 to 12 months postpartum, among primiparous PE women. Participants will be allocated either a bundle intervention or standard care. The intervention includes a combination of information, targeted screening and healthy lifestyle promotion, including physical activity and a healthy diet through support by study personnel and an interactive Smartphone-App. The primary outcome will be change in BMI between baseline and follow-up. Significance: Clinically, this group of women with increased CVD-risks is often left without support. If the bundle intervention proves to be superior to standard care, implementation of the program into clinical care could improve the cardiometabolic profile of women with previous PE and potentially prevent future CVD. Furthermore, the intervention could be expanded to women with other pregnancy complications associated to CVD and parous women with PE.