BACKGROUND: This study aims to develop a prediction model to identify individuals at risk of hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, by integrating epigenetic biomarkers and clinical factors in the first trimester of pregnancy. METHODS: A 2-stage nested case-control study, matched by age and body mass index, was conducted with 618 pregnant women in China, with peripheral blood samples collected in the first trimester to evaluate the average methylation levels of differentially methylated regions (DMRs) between controls and HDP cases. In stage 1 (discovery set), 24 controls and 27 cases were used to identify the differential DMRs. In stage 2, 294 controls and 273 cases were used to validate the previously identified DMRs. DMRs selected from the intersectional results of lasso regression, XGBoost, random forest, and Shapley Additive Explanations models were further combined with women’s clinical risk factors to construct prediction models using logistic regression. RESULTS: In stage 1, 52 differential DMRs were identified with a false-positive rate <0.05. In stage 2, 12 differential DMRs were consistently observed, and 3 DMRs located in the CTSA , HMGB1 , and miR1908/FADS2 genes were selected to construct a prediction model for HDPs. After combining the selected DMRs with clinical factors, the model achieved an area under the curve of 0.863 (95% CI, 0.826–0.901) in the training set and 0.757 (95% CI, 0.686–0.828) in the test set. CONCLUSION: Findings of this study offer potential opportunities to identify high-risk patients with HDP in early pregnancy through DMRs identified in peripheral blood and provide new insights into the epigenetic cause of HDP.

Background: In addition to hyperglycemia, women with hypoglycemia identified during pregnancy have a higher risk of adverse pregnancy outcomes. However, there is limited evidence of the association between prepregnant hypoglycemia and adverse pregnancy outcomes in women without pre-existing diabetes. This study aims to explore the association between maternal preconception hypoglycemia and adverse pregnancy outcomes among childbearing-aged women in China. Methods and findings: This was a retrospective cohort study of the National Free Preconception Checkup Project (NFPCP), including women who were aged 20–49, successfully conceived within one year without multiple gestations, and had complete information on pregnancy outcomes. Maternal fasting plasma glucose (FPG) concentrations were analyzed in the preconception examination stage, and women were divided into normal (FPG 3.9 to <5.6 mmol/L) and hypoglycemia (FPG < 3.9 mmol/L) groups. Adverse pregnancy outcomes included medical abortion, miscarriage or early stillbirth, preterm birth (PTB), macrosomia, low birth weight (LBW), large for gestational age (LGA), small for gestational age (SGA), birth defects, and perinatal death. Baseline characteristics of the two groups were balanced using inverse probability treatment weighting (IPTW) based on propensity scores. Both multivariable-adjusted and IPTW odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between preconception hypoglycemia and adverse pregnancy outcomes. Models adjusted for maternal age, ethnicity, educational level, occupation, region of gross domestic product, smoking, passive smoking, alcohol consumption, maternal preconception body mass index (BMI), parity, history of adverse pregnancy outcome, preconception medicine use, folic acid intake, diabetes, hypertension, anemia, thyroid disorder, liver disorder, and infection. ORs of adverse pregnancy outcomes with preconception hypoglycemia stratified by BMI were also reported. Among 4,866,919 women who participated in NFPCP during 2013–2016, 239,128 (4.91%) had preconception hypoglycemia. Compared to the normal group, women with preconception hypoglycemia had increased IPTW-multivariate adjusted ORs of PTB by 10% (95% CI [1.08, 1.12], P < 0.001), LBW by 8% (95% CI [1.03, 1.12], P = 0.001), SGA by 7% (95% CI [1.05, 1.08], P < 0.001), and birth defects by 21% (95% CI [1.06, 1.37], P = 0.004), while the ORs of medical abortion decreased by 6% (95% CI [0.91, 0.98], P = 0.002), miscarriage or early stillbirth by 5% (95% CI [0.92, 0.97], P < 0.001), macrosomia by 12% (95% CI [0.86, 0.90], P < 0.001), and LGA by 12% (95% CI [0.86, 0.89], P < 0.001) if mothers had a preconception hypoglycemia. The associations of maternal preconception hypoglycemia and adverse pregnancy outcomes varied among BMI groups. Among underweight women, preconception hypoglycemia was associated with a lower risk of medical abortion, miscarriage or early stillbirth, LGA, and PID, while overweight women had a lower risk of macrosomia and LGA. Moreover, a higher risk of miscarriage or early stillbirth and PTB was observed in obesity and underweight, respectively, in association with preconception hypoglycemia. Main limitations in the current study included the limited generalizability in other countries with varying disparities in healthcare and the lack of information on certain potential confounders (such as gestational complications and whether they received any related intervention after preconception examination). Conclusion: Preconception hypoglycemia was significantly associated with adverse pregnancy outcomes, and maternal preconception BMI could modify the association. In addition to paying attention to women with preconception hyperglycemia, our findings call for increased concern for women with hypoglycemia in preconception glycemic screening, with consideration of modified effects by preconception BMI, which might be worth exploring as a means to reduce adverse pregnancy outcomes.

Background/Objectives: Patient navigation is vital for improving healthcare accessibility and patient experience in China’s public hospitals, where high patient demand meets limited medical resources. Patient navigators (PNs) assist patients through the complex healthcare system, but the lack of standardized training and evaluation hampers their ability to meet patient needs. This study piloted a Competencies Improvement Training Program (CITP) in a tertiary hospital to clarify PN competencies, design a feasible curriculum, assess its efficacy, and share insights with peer hospitals. Methods: The CITP used the Plan–Do–Check–Act (PDCA) framework and designed a curriculum with Miller’s Pyramid Model. Over 6 months, eight sessions were conducted, including theory, case studies, etc. The quasi-experimental design compared PN competencies and patient satisfaction before and after. Multiple instruments measured baseline competencies and program efficacy with a 6-month post-training follow-up. Results: A total of 75 PNs (75%) participated and completed all sessions. A total of 1189 patients were surveyed before training, 495 in the first month after training, and 502 in the 6-month follow-up. The CITP significantly boosted PN competency scores from 90.259 to 95.453, though it dipped to 92.721 by 6 months. Patient satisfaction with PN services improved modestly over 6 months. Challenges in applying theoretical knowledge to practical skills were noted, suggesting differentiated training based on navigator demographics. Patient satisfaction for aspects like politeness and tone was linked to patient age and education. Conclusions: The CITP enhanced PN core competencies and provided an evidence-based curriculum model. Future research should involve larger multi-center populations with longer-term follow-ups to validate the program’s effectiveness across diverse settings.

Introduction: Hepatitis B virus (HBV) has recently been reported to impair both sperm and oocyte function, potentially increasing infertility and birth defects risks, although primarily recognised as a concern for mother-to-child transmission. Population-based evidence regarding the association between paternal preconception HBV infection and preterm birth (PTB) risk is absent. Methods: This retrospective cohort study was conducted based on the National Free Preconception Checkups Project between 22 April 2010 and 31 December 2020 in China. Paternal preconception HBV infection statuses were divided into three groups: uninfected, past exposure and immunity, and current infection. Inverse probability weighting (IPW) via propensity models was used to adjust for imbalance by different groups of paternal preconception HBV infection status. Log-binomial regression models were employed to estimate the relative risk ratios (RRs) of PTB associated with paternal preconception HBV infection. Results: 7 395 829 couples were included, with a PTB incidence of 5.65%. Compared with HBV-uninfected males, those with prior HBV exposure had a 5% increased PTB risk in offspring (RR 1.05, 95% CI 1.04 to 1.07), and those infected with HBV currently showed a 10% increased PTB risk (RR 1.10, 95% CI 1.09 to 1.12). No significant association was observed when both partners had the same HBV immunity prior to pregnancy (RR 1.01, 95% CI 0.99 to 1.03). Moreover, an interaction effect between maternal and paternal preconception HBV infection was observed ( P _{for interaction} =0.003), with couples both currently infected with HBV showing the highest PTB risk (RR 1.16, 95% CI 1.11 to 1.20). Consistent results were obtained across all PTB subtypes. Conclusions: Both paternal current HBV infection and prior exposure were identified to be associated with increased PTB risks independently. Moreover, the interaction impact of HBV infections between couples on PTB risks should also be considered. These findings provide new evidence for the paternal risk factors of PTB, highlighting the importance of comprehensive HBV screening and immunity management for both parents before conception to reduce PTB risks.