Objective We aimed to develop and validate an effective prediction model for hypertensive disorder of pregnancy (HDP) in twin pregnancies after 28 weeks of gestation. Design Retrospective cohort study. Setting Maternity hospital. Participants We recruited twin pregnancies who delivered in Fujian Maternity and Child Health Hospital from January 2014 to December 2019 as a training cohort. Besides, we included twin pregnancies delivered at Fujian Maternity and Child Health Hospital; Women and Children’s Hospital of Xiamen University from January 2020 to December 2021 as temporal validation set and geographical validation set, respectively. Main outcome measures We performed univariate analysis, the least absolute shrinkage and selection operator regression and Boruta algorithm to screen variables. Then, we used multivariate logistic regression to construct a nomogram that predicted the risk of HDP in twin pregnancies. We employed the bootstrap resampling method for internal validation, used the receiver operating characteristic (ROC) curve to evaluate the predictive performance of the model and constructed decision curve analysis to assess the clinical benefit of the model. Thereafter validated the nomogram through the index of concordance (C-index) and calibration curves in the temporal validation set and geographical validation set. Results Multivariate logistic regression showed that primipara (OR=1.284, 95% CI=1.016 to 1.622), the higher pre-pregnancy body mass index (OR=1.077, 95% CI=1.039 to 1.116), the higher uric acid (OR=1.004, 95% CI=1.002 to 1.005), the higher urea nitrogen (OR=1.198, 95% CI=1.087 to 1.321), the higher creatinine (OR=1.011, 95% CI=1.002 to 1.020), the higher lactate dehydrogenase (OR=1.001, 95% CI=1.000 to 1.002), the higher ratio of large platelets (OR=1.034, 95% CI=1.020 to 1.048), the lower albumin (OR=0.887, 95% CI=0.852 to 0.924), the lower calcium (OR=0.148, 95% CI=0.058 to 0.375) are influencing factors of HDP in twin pregnancies. The area under the ROC curve of the prediction model was 0.763. The C-index were 0.842 and 0.746, respectively, on the temporal validation set and geographical validation set. Conclusions The new model for predicting HDP in twin pregnancies constructed by clinical characteristics and laboratory indicators had high clinical application value. It can be used to individually evaluate the occurrence of HDP in twin pregnancies after 28 weeks of gestation.

Preeclampsia (PE), characterized by new‐onset hypertension and proteinuria after 20 weeks of gestation, presents substantial risks to both mother and fetus. Cuproptosis represents a newly identified form of regulated cell death; its potential association with PE pathogenesis remains unclear. We retrieved the GSE60438 dataset from the GEO database and identified 557 differentially expressed genes (DEGs) associated with PE. Weighted gene co‐expression network analysis (WGCNA) was performed, and by intersecting the DEGs with WGCNA module genes, we obtained 198 candidate PE‐related genes. KEGG and GO enrichment analyses revealed their potential biological functions, with significant enrichment in lipoic acid metabolism, the tricarboxylic acid (TCA) cycle, and components of the mitochondrial matrix. By further intersecting the DEGs, WGCNA module genes, and cuproptosis‐related genes, we identified DLD as the hub cuproptosis‐related gene in PE. GSEA further revealed its involvement in key metabolic pathways. The expression of DLD in PE and normal placental tissues was detected by qRT‐PCR and immunohistochemical staining. Loss or gain‐of‐function tests were performed to assess the effects of DLD on the proliferation, migration, and invasion of HTR‐8/SVneo cells. Concurrently, pyruvate and citrate levels were quantified with commercial kits, and intracellular ultrastructure was examined by transmission electron microscopy. Herein, we detected increased DLD in the PE placental tissues. In vitro studies showed that knockdown of DLD promoted trophoblast proliferation, migration, and invasion; conversely, overexpression of DLD showed the opposite effect. Concurrently, DLD overexpression induced metabolic dysregulation in tricarboxylic acid (TCA) cycle intermediates as well as distinct mitochondrial ultrastructural alterations. Our study demonstrated that DLD, a cuproptosis‐related gene, is significantly upregulated in PE and functionally impairs trophoblast activity, suggesting its pathogenic role may be mediated through cuproptosis.

Preeclampsia is a serious pregnancy-specific complication and a major cause of perinatal morbidity. While inflammatory markers have been associated with preeclampsia in singleton pregnancies, their role in twin pregnancies remains poorly understood. This study aimed to explore the relationship between inflammatory markers and preeclampsia in twin pregnancies. In this retrospective cohort study, we recruited 2712 women with twin pregnancies who delivered at Fujian Maternal and Child Health Hospital from January 2014 to December 2021. Participants were divided into control group (n = 2200), gestational hypertension group (n = 126) and preeclampsia group(n = 386). We compared baseline data and inflammatory markers between groups. The correlation between inflammatory markers and preeclampsia in twin pregnancies was further analyzed using logistics regression adjusted for confounders. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship. Systemic immune inflammation index (SII), monocyte/high-density lipoprotein ratio (MHR), lymphocyte/high-density lipoprotein ratio (LHR) and platelet-to-lymphocyte ratio (PLR) exhibited statistical significance between the preeclampsia and control groups. Smooth curve fitting indicated that the relationships between SII, MHR and PLR with preeclampsia were nonlinear. After full adjustment, breakpoints were found to be 666.32, 0.84 and 88.28, respectively. Decreased levels of SII, PLR and increased levels of MHR levels were associated with greater prevalences of PE before the breakpoints. The relationships between SII, MHR and PLR with preeclampsia were nonlinear. Twin pregnancies with decreased levels of SII, PLR and elevated levels of MHR should be attentive to the potential risks to preeclampsia before their thresholds.

Background We aimed to investigate risk factors of adverse maternal outcomes associated with preeclampsia (PE) in twin pregnancies and develop a simplified clinical prediction model. Method We recruited pregnant women with preeclampsia who were hospitalized in Fujian Maternal and Child Health Hospital from January 2014 to December 2021, including singleton and twin pregnancies. We further divided twin pregnancies into adverse outcome group and non-adverse outcome group. We performed univariate analysis, the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis to identify factors influencing adverse maternal outcomes associated with preeclampsia in twin pregnancies, then established a predictive model. The predictive performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, calibration plots and decision curve analysis (DCA). Results Twin pregnancies with PE showed a higher prevalence of adverse outcomes compared with singleton pregnancies (17.4% VS 13.6%). Gestational age at admission less than 32 + 0 week gestational age, multipara, peak systolic blood pressure, creatinine, neutrophil/high-density lipoprotein ratio (NHR)and decreased platelet count were independent risk factors for the development of adverse outcomes of PE in twin pregnancies. The area under the ROC curve of the prediction model was 0.798 and the calibration curve indicated that adverse maternal outcomes rate predicted by the model was consistent with the actual outcome. Conclusions The predictive model can identify women at increased risk of adverse maternal outcomes associated with preeclampsia in twin pregnancies, which can provide suggestion for preeclampsia in twin pregnancies and intervening timely.