An association between maternal preeclampsia and an increased risk of cardiovascular disease in the offspring is plausible, but evidence in this area is limited.
Objective
To investigate (1) the association between maternal preeclampsia and risks of ischemic heart disease (IHD) and stroke in the offspring, (2) whether the association varies by severity or timing of onset of preeclampsia, and (3) the role of preterm birth and small for gestational age (SGA) birth, both of which are related to preeclampsia and cardiovascular diseases, in this association.
DESIGN, SETTING, AND
Participants
This multinational population-based cohort study obtained data from Danish, Finnish, and Swedish national registries. Live singleton births from Denmark (1973-2016), Finland (1987-2014), and Sweden (1973-2014) were followed up until December 31, 2016, in Denmark and December 31, 2014, in Finland and Sweden. Data analyses were performed between September 2020 and September 2022.
EXPOSURES: Preeclampsia and its subtypes, including early onset (<34 gestational weeks) and late onset (≥34 gestational weeks), severe and mild or moderate, and with and without SGA birth.
MAIN OUTCOMES AND
Measures
Diagnoses of IHD and stroke were extracted from patient and cause-of-death registers. Cox proportional hazards regression models and flexible parametric survival models were used to analyze the associations. Sibling analyses were conducted to control for unmeasured familial factors.
Results
The cohort included of 8 475 819 births (2 668 697 [31.5%] from Denmark, 1 636 116 [19.3%] from Finland, and 4 171 006 [49.2%] from Sweden, comprising 4 350 546 boys [51.3%]). Of these offspring, 188 670 (2.2%) were exposed to maternal preeclampsia, 7446 (0.1%) were diagnosed with IHD, and 10 918 (0.1%) were diagnosed with stroke during the median (IQR) follow-up of 19.3 (9.0-28.1) years. Offspring of individuals with preeclampsia had increased risks of IHD (adjusted hazard ratio [HR], 1.33; 95% CI, 1.12-1.58) and stroke (adjusted HR, 1.34; 95% CI, 1.17-1.52). These associations were largely independent of preterm or SGA birth. Severe forms of preeclampsia were associated with a higher stroke risk than less severe forms (severe vs mild or moderate: adjusted HR, 1.81 [95% CI, 1.41-2.32] vs 1.22 [95% CI, 1.05-1.42]; early vs late onset: adjusted HR, 2.55 [95% CI, 1.97-3.28] vs 1.18 [95% CI, 1.01-1.39]; with vs without SGA birth: adjusted HR, 1.84 [95% CI, 1.44-2.34] vs 1.25 [95% CI, 1.07-1.48]). Sibling analyses suggested that the associations were partially explained by unmeasured familial factors.
CONCLUSIONS AND RELEVANCE: Results of this study suggest that offspring born to individuals with preeclampsia had increased IHD and stroke risk that were not fully explained by preterm or SGA birth, and that the associated risks for stroke were higher for severe forms of preeclampsia.
PMID 36378310 36378310 DOI 10.1001/jamanetworkopen.2022.42064 10.1001/jamanetworkopen.2022.42064 Yang et al. 2022, Yang 2022
Cite this article
Yang, F., Janszky, I., Gissler, M., Roos, N., Wikström, A. K., Yu, Y., Chen, H., Bonamy, A. E., Li, J., & László, K. D. (2022). Association of Maternal Preeclampsia With Offspring Risks of Ischemic Heart Disease and Stroke in Nordic Countries.. JAMA network open, 5(11), e2242064. https://doi.org/10.1001/jamanetworkopen.2022.42064
Yang F, Janszky I, Gissler M, Roos N, Wikström AK, Yu Y, Chen H, Bonamy AE, Li J, László KD. Association of Maternal Preeclampsia With Offspring Risks of Ischemic Heart Disease and Stroke in Nordic Countries.. JAMA network open. 2022;5(11):e2242064. doi:10.1001/jamanetworkopen.2022.42064
The Mediterranean diet pattern is inversely associated with the leading causes of morbidity and mortality, including metabolic diseases and cardiovascular disease, but there are limited data on its association with adverse pregnancy outcomes (APOs) among US women. To evaluate whether concordance to a Mediterranean diet pattern around the time of conception is associated with lower risk of developing any APO and individual APOs. DESIGN, SETTING, This prospective, multicenter, cohort study, the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, enrolled 10 038 women between October 1, 2010, and September 30, 2013, with a final analytic sample of 7798 racially, ethnically, and geographically diverse women with singleton pregnancies who had complete diet data. Data analyses were completed between June 3, 2021, and April 7, 2022. An Alternate Mediterranean Diet (aMed) score (range, 0-9; low, 0-3; moderate, 4-5; and high, 6-9) was computed from data on habitual diet in the 3 months around conception, assessed using a semiquantitative food frequency questionnaire. Adverse pregnancy outcomes were prospectively ascertained and defined as developing 1 or more of the following: preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, delivery of a small-for-gestational-age infant, or stillbirth. Of 7798 participants (mean [SD] age, 27.4 [5.5] years), 754 (9.7%) were aged 35 years or older, 816 (10.5%) were non-Hispanic Black, 1294 (16.6%) were Hispanic, and 1522 (19.5%) had obesity at baseline. The mean (SD) aMed score was 4.3 (2.1), and the prevalence of high, moderate, and low concordance to a Mediterranean diet pattern around the time of conception was 30.6% (n=2388), 31.2% (n=2430), and 38.2% (n=2980), respectively. In multivariable models, a high vs low aMed score was associated with 21% lower odds of any APO (adjusted odds ratio [aOR], 0.79 [95% CI, 0.68-0.92]), 28% lower odds of preeclampsia or eclampsia (aOR, 0.72 [95% CI, 0.55-0.93]), and 37% lower odds of gestational diabetes (aOR, 0.63 [95% CI, 0.44-0.90]). There were no differences by race, ethnicity, and prepregnancy body mass index, but associations were stronger among women aged 35 years or older (aOR, 0.54 [95% CI, 0.34-0.84]; P = .02 for interaction). When aMed score quintiles were evaluated, similar associations were observed, with higher scores being inversely associated with the incidence of any APO. This cohort study suggests that greater adherence to a Mediterranean diet pattern is associated with lower risk of APOs, with evidence of a dose-response association. Intervention studies are needed to assess whether dietary modification around the time of conception can reduce risk of APOs and their downstream associations with future development of cardiovascular disease risk factors and overt disease.
Regulatory T cells (Tregs) play a central role in maintaining immune tolerance and supporting maternal-fetal homeostasis throughout human pregnancy. Clinical and experimental evidence demonstrates that dysregulation of peripheral and decidual Tregs manifested as quantitative deficits, impaired suppressive function or lineage instability increased the risk of various pathological pregnancies, such as recurrent implantation failure (RIF), recurrent spontaneous abortion (RSA), pre-eclampsia (PE) and preterm birth (PTB). Recently, novel therapeutic strategies targeting Tregs have emerged in oncology, transplantation, and autoimmune diseases. However, their application in pathological pregnancy remains in its infancy. This review outlines the spatiotemporal dynamics of peripheral and decidual Tregs throughout gestation, elucidating their roles in maintaining maternal-fetal homeostasis and their dysregulation in pathological pregnancies. We also critically evaluated the therapeutic strategies targeting Tregs and Tregs-associated signaling pathways, including hormonal support, traditional intravenous immunoglobulin, as well as emerging interventions such as immunometabolic reprogramming and engineered cellular therapies like chimeric antigen receptor Tregs. This review may provide insights for understanding the roles of Tregs in physiological and pathological pregnancy, as well as provide new idea in the immunotherapy of pathological pregnancy.
Johnson J et al., 2025·Journal of Assisted Reproduction and Genetics
The human placenta plays an important role in pregnancy and offspring health. The paternal genome contributes significantly to placental growth and development. While the maternal factors affecting gestational health are thoroughly investigated, the paternal factors are often overlooked. Thus, it is important to understand various paternal factors affecting placental development and function. To assess the effect of various paternal factors on placental development, function, and pregnancy-related disorders. This review was registered in PROSPERO (Registration number CRD420250634649). Literatures across databases like JSTOR, Scopus, Google Scholar, ScienceDirect, and PubMed were screened through a set of criteria. Forty-eight studies were selected that included low-to-moderate risk paternal factors like age, smoking, race/ethnicity/location, genetic, epigenetic factors, exposure to chemicals, seminal plasma, and lifestyle factors. Increased paternal age was reported to contribute towards higher risks of preeclampsia, spontaneous abortions, preterm birth, stillbirth, and higher placental and fetal birth weight. Paternal smoking, on the other hand, was found to be an associated risk factor for placental abruption and stillbirth. Exposure to various chemicals was found to be associated with changes in sperm epigenome and placental dysfunction. Discussion and Paternal health, lifestyle, and exposure to chemicals may affect placental development and pregnancy. Paternal factors may alter seminal plasma proteome, cytokine profile, and abnormal sperm DNA methylation of imprinted genes which is associated with adverse pregnancy outcomes. Pre-conceptional health assessment of prospective fathers might be helpful in ensuring optimal placental development in pregnancies to follow, in addition to newborn health.
Prescribing Safety · Medication Safety in Pregnancy
Murvai VR et al., 2025·BMC pregnancy and childbirth·
Open Access
Antiphospholipid syndrome (APS) is an autoimmune disorder associated with thrombotic events and adverse obstetric outcomes, particularly in its obstetric form (OAPS). Affecting approximately 0.5% of the population, APS is a leading contributor to recurrent pregnancy loss (RPL), preeclampsia (PE), and fetal growth restriction ((FGR). Despite advancements in understanding its pathophysiology and management, optimal treatment strategies for APS in pregnancy remain challenging and require systematic evaluation. This review synthesizes current evidence on APS mechanisms, diagnostic criteria, and therapeutic interventions, with a focus on maternal and fetal outcomes in OAPS. A comprehensive search of PubMed, was conducted to identify studies exploring APS pathogenesis, diagnostic standards, and treatment efficacy in obstetric settings. Inclusion criteria prioritized randomized controlled trials, cohort studies, and systematic reviews with a clear focus on APS and pregnancy. The review confirmed that APS current accepted pathogenesis is governed by a "two-hit" model, where antiphospholipid antibodies (aPLs) initiate endothelial damage, culminating in thrombosis and placental insufficiency. Epidemiological analysis underscores the prevalence and severity of APS in obstetric contexts, with lupus anticoagulant (LA) emerging as a significant predictor of adverse outcomes. Evidence supports the use of low-dose aspirin (LDA) and heparin to reduce miscarriage rates, while adjunctive treatments, such as hydroxychloroquine (HCQ), have shown promise in improving live birth rates and reducing preterm delivery in high-risk cases. Emerging therapies, including tumoral necrosis factor (TNF-alpha) inhibitors and nitric oxide modulators, may offer additional benefits in refractory cases. APS remains a critical determinant of adverse pregnancy outcomes, necessitating precise diagnostic criteria and tailored management approaches. This systematic review emphasizes the importance of individualized therapeutic regimens to optimize maternal and fetal health in OAPS and highlights areas for future research, particularly regarding novel pharmacological approaches. Further studies are essential to refine treatment protocols and improve clinical guidelines for managing APS in pregnancy.