Pregnancies conceived using in vitro fertilization (IVF) significantly increase the risk of developing preeclampsia. One possible explanation is that embryos grown outside the body may implant differently compared to natural conceptions, potentially affecting placental development and increasing the risk of preeclampsia. Clinically, preeclampsia is classified into early-onset and late-onset forms, as well as severe and mild forms. Although some studies suggested that preeclampsia severity may be more pronounced in IVF-conceived pregnancies, the findings were controversial. In this retrospective study, we compared the severity of preeclampsia between naturally conceived and IVF-conceived pregnancies. A total of 498 preeclampsia cases were included, with 401 cases occurring in naturally conceived pregnancies and 97 in IVF-conceived pregnancies. The mean gestational age at delivery in the IVF-conceived group was 36 weeks, significantly earlier than that in the naturally conceived group (37 weeks, p = 0.0002). Additionally, 27 (28%) women in the IVF-conceived group developed early-onset preeclampsia, which was no statistical difference from the naturally conceived group (78, 19%, p = 0.0732). There was no significant difference in the proportion of severe preeclampsia between the two groups (16% vs. 23%, p = 0.1667). Additionally, gestational age at the onset of preeclampsia and the incidence of preterm birth were not different between the two groups after adjusting for important confounders, including maternal age, BMI, parity, and twin pregnancy. In conclusion, there is a known link between IVF conception and the increased risk of developing preeclampsia. Our study found that the severity of preeclampsia, once it occurred, did not differ between the two modes of conception.
Objectives To investigate an association of inter-arm blood pressure differences (IAD) and within-visit variability of blood pressure in early pregnancy with pre-eclampsia.Methods Blood pressure information was available on 8117 participants from the prospective PREeclampsia Screening In DEnmark (PRESIDE) study. Three consecutive blood pressure (BP) measurements were taken on both arms simultaneously in participants attending the first-trimester ultrasound. Maternal characteristics, medical history, and pregnancy outcome were collected. Outcomes were pre-eclampsia overall, further stratified into preterm (delivery < 37 weeks of gestation) and term cases (delivery ≥ 37 weeks of gestation).Results Women developing pre-eclampsia had a higher diastolic IAD (2.67 mmHg vs 2.33 mmHg) and pulse pressure IAD (4.67 mmHg vs 4.33 mmHg OR 1.04 (95% CI: 1.01; 1.07)). Pulse pressure IAD was associated with pre-eclampsia (adjusted OR 1.04, 95% CI 1.01, 1.07) and term pre-eclampsia (OR 1.05, 95 % CI 1.02, 1.08), but not with preterm pre-eclampsia (OR 0.99, 95% CI 0.9, 1.06). There were no associations between systolic IAD, within-visit BP variability and pre-eclampsia.Conclusion Diastolic IAD and pulse pressure IAD in early pregnancy were higher in women developing pre-eclampsia. No association was found between systolic IAD or within-visit BP variability and pre-eclampsia.
Preeclampsia is a pregnancy-specific hypertensive disorder characterized by new-onset hypertension after 20 weeks of gestation, accompanied by end-organ dysfunction with or without proteinuria. Affecting approximately 5–7% of pregnancies worldwide, it remains a leading cause of maternal and fetal morbidity and mortality. Despite decades of research, the underlying pathophysiology of preeclampsia remains incompletely understood. However, increasing evidence implicates placental mitochondrial oxidative stress in its pathogenesis. In this review, we summarize the current literature pertaining to ultrastructural evidence of mitochondrial damage, defects in oxidative phosphorylation and electron transport chain activity, and alterations in reactive oxygen species production, antioxidant defense, and mitochondrial biogenesis. Finally, we discuss translational considerations and highlight how therapeutic strategies targeted at restoring mitochondrial function may represent a promising approach for managing preeclampsia.
Hypertensive disorders of pregnancy (HDP) encompass chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia superimposed on chronic hypertension, affecting about 5% to 10% of pregnancies worldwide and remaining a major cause of maternal and perinatal morbidity and mortality. Their burden is increasing with rising obesity, advanced maternal age, evolving diagnostic criteria, and marked socioeconomic and racial-ethnic disparities. This review summarises current evidence on the epidemiology, pathophysiology, biomarkers, clinical management, and long-term outcomes of HDP, highlighting recent advances and unresolved questions. Mechanistically, HDP is characterised by systemic endothelial dysfunction and angiogenic imbalance, particularly involving soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng), together with immune maladaptation, oxidative stress, and genetic and environmental contributors such as endocrine-disrupting chemicals (EDCs) and sleep-disordered breathing (SDB). The sFlt-1/PlGF ratio is among the most validated tools for short-term risk assessment in suspected preeclampsia, while retinal microvascular imaging may provide a non-invasive marker of systemic microvascular dysfunction. Clinically, trial evidence supports treating mild chronic hypertension to below 140/90 mmHg to reduce adverse outcomes without compromising foetal growth. Long-term maternal cardiovascular and metabolic risks vary according to HDP phenotype, severity, gestational age at onset, and associated preterm delivery or foetal growth restriction, whereas offspring neurodevelopmental associations are largely observational and may be influenced by prematurity and shared familial or socioeconomic factors. Experimental strategies supported primarily by preclinical or early translational evidence include PPARγ agonists, placenta-targeted nanomedicine, and transcutaneous auricular vagus nerve stimulation. Machine learning combined with longitudinal multi-omics data may support precision risk stratification and individualised management.
Introduction SARS-CoV-2 infection during pregnancy has been associated with higher rates of preeclampsia (PE). While placental abnormalities resembling PE have been reported in COVID-19 pregnancies, the molecular mechanisms underlying the association remain unclear. Methods We conducted bulk RNA sequencing on placental tissues from four pregnancy groups: uneventful prepandemic (preCOVID-19), prepandemic PE (preCOVID-19 PE), COVID-19 without PE (COVID no PE), and COVID-19 complicated by PE or other hypertensive disorders (COVID PE). Differential expression was analyzed using Deseq2 likelihood ratio test (LRT), and gene set enrichment analysis identified dysregulated pathways.Results Clustering of LRT-significant differentially expressed genes (DEGs) identified a set of 16 genes (defined by the false discovery rate adjusted p-value < 0.05) across the four pregnancy groups, showing stepwise expression changes-lowest in preCOVID-19 uneventful, followed by those in COVID-19 without PE, then preCOVID-19 PE, and highest in COVID PE. This cluster included genes associated with placental dysfunction, such as LAMA5 and BTNL9. While morphogenesis-related pathways were enriched across all pathological groups, immune activation pathways were predominantly enriched in COVID PE, moderately in preCOVID-19 PE, and absent in COVID no PE.Discussion Our findings identify a COVID-19-associated placental signature that mirrors PE features and shows a progressive expression pattern defining a continuum of placental stress, with maternal SARS-CoV-2 infection potentially exacerbating underlying dysfunction.
