Hanbin Wu

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 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 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.

Aims/hypothesis: The study aimed to explore the association between maternal glucose levels in pregnancy and offspring’s metabolism and adiposity at approximately 18 years of age. Methods: Pregnant women from the Hong Kong Field Centre enrolled in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study underwent a 75 g OGTT at 24–32 gestational weeks. Offspring’s metabolic and adiposity traits were assessed at 18 years postpartum. Associations were evaluated using multiple linear regression and logistic regression. Results: Among the 506 mother–child pairs followed up to 18 years, maternal fasting plasma glucose (FPG) in pregnancy was positively associated with offspring’s FPG (β = 0.06 [95% CI 0.02, 0.09]), while maternal 1 h plasma glucose (PG) showed a positive association with offspring’s FPG (β = 0.05), 30 min PG (β = 0.21) and 2 h PG (β = 0.14). All maternal glycaemic levels were associated with an increased risk of offspring being overweight/obese, particularly maternal 1 h PG (OR 1.50 [95% CI 1.17, 1.93]). Offspring of mothers with gestational diabetes mellitus showed a higher prevalence of abnormal glucose tolerance (11.86% vs 7.97%), impaired fasting glucose (1.89% vs 0.49%) and impaired glucose tolerance (10.34% vs 7.13%) than offspring of mothers with normal glucose tolerance, although these associations did not reach statistical significance in fully adjusted models, underscoring the benefit of considering maternal glucose as a continuous trait. Conclusions/interpretation: Maternal glucose levels in pregnancy showed a long-term association with offspring’s metabolic health into young adulthood, with continuous associations across the full maternal glucose spectrum, suggesting a graded effect of maternal hyperglycaemia on offspring’s metabolic risk. Graphical

Early-life exposures may shape long-term effects on glucose regulation. This study aimed to stratify long-term abnormal glucose tolerance (AGT) risk from early childhood. A total of 906 children were enrolled at baseline and reevaluated in adolescence and young adulthood. By using the latent class trajectory analysis, glucose trajectories of children were measured via five–time point oral glucose tolerance tests and then grouped into three latent subclasses: mild excursion–normal reversion (MN), moderate excursion–delayed reversion (MD), and severe excursion–delayed reversion (SD). Logistic regression was performed to estimate the risk of AGT and associations between cardiometabolic factors and subclasses. In adolescence, compared with the MN subclass, the risk of AGT was 1.7-fold in the MD subclass and 5.5-fold in the SD subclass, after adjusting for age, sex, BMI, and Tanner stage. In young adulthood, the adjusted risk of AGT was 3.6-fold and 11.6-fold in the MD and SD subclasses, respectively. During the full natural history of glucose tolerance, the risk of AGT was 3.6-fold in the MD subclass and 18.1-fold in the SD subclass, after adjusting for childhood covariates. MD and SD subclass membership was strongly associated with childhood hypertension, maternal gestational diabetes, and maternal hypertension during pregnancy. Glucose trajectory subclasses in early childhood effectively stratified the long-term risk of AGT. The association between maternal cardiometabolic health and childhood subclass membership highlighted that prenatal exposures may influence metabolic outcomes in offspring. ARTICLE HIGHLIGHTS: Abnormal glucose tolerance (AGT) in youth has become an alarming global public health issue; however, approaches to identify high-risk population among young people have not been well-established. Can the long-term risk of AGT be stratified by the subclasses of glucose trajectories defined in childhood? Subclasses defined in childhood can efficiently stratify the risk of AGT in adolescence and young adulthood. The subclass membership was strongly associated with cardiometabolic disorders in childhood and maternal cardiometabolic disorders during pregnancy. This subclass method provides a potential strategy to identify those at risk of later cardiometabolic disorders from childhood for more intensive evaluation of intervention. The close relationship between maternal cardiometabolic disorders and subclass membership of children highlighted the potential influence of gestational cardiometabolic health on the development of cardiometabolic disorders in offspring.

Objective To explore the association of clinical and subclinical bacterial vaginosis before conception with the risk of spontaneous abortion. Design Retrospective cohort study. Setting Mainland China. Population This study included women who enrolled in and completed the National Free Pre-Pregnancy Checkups Project between January 1, 2014 and December 31, 2018. Methods Clinical bacterial vaginosis before conception was diagnosed according to the Amsel criteria, and subclinical bacterial vaginosis before conception was defined as any indicators in the Amsel Criteria being positive but not meeting the diagnostic criteria. Analyses were performed by multivaribale-adjusted logistic models with crude and multivaribale-adjusted odds ratios including 95% confidence interval. Main outcome measures Spontaneous abortion was defined as fetal death occurring spontaneously before the 28th week of gestation. Results Of the included participants, 0.27% and 6.97% of them had clinical and subclinical bacterial vaginosis before conception respectively. A significantly increased risk of spontaneous abortion was observed for women with preconception bacterial vaginosis (OR: 1.19, 95% CI: 1.06-1.34). After excluding participants with preconception bacterial vaginosis, subclinical bacterial vaginosis was associated with a 15% (13%-18%) increased risk of spontaneous abortion. And the corresponding multivariable-adjusted ORs of exposure to abnormal vaginal discharge characteristics, vaginal pH value ≥4.5, positive clue cell test, and positive Whiff test for spontaneous abortion were 1.20 (1.03-1.39), 1.15 (1.12-1.18), 1.08 (0.97-1.19), and 1.24 (1.11-1.38). Conclusion Both clinical and subclinical bacterial vaginosis before conception were prospectively associated with an increased risk of spontaneous abortion.

Sexually active young people face an increasing public health burden of unintended pregnancies and sexually transmitted diseases due to improper contraception. However, environmental and social factors related to young people’s contraception remain unclear. To identify the key factors, we applied ensemble machine learning methods to the data of 12,280 heterosexual Chinese college students who reported sexual intercourse experience in the National College Student Survey on Sexual and Reproductive Health in 2020 (NCSS-SRH 2020). In the order of variable importance, convenient access to contraceptives, certain attitudes towards sex, sexual health knowledge level, being an only-child, and purchasing a bachelor’s or master’s degree were positively associated with a high frequency of contraceptive use. In contrast, smoking, free access to contraceptives, a specific attitude towards marriage, and negotiation with a sexual partner were negatively associated with a higher frequency of contraceptive use. Our analysis provides insights into young people’s contraceptive use under a typically conservative culture of sexuality. Compared to previous studies, we thoroughly investigated internal and external factors that might impact young people’s decision on contraception while having sex. Under a conservative culture of sexuality, the effects of the external factors on young people’s contraception may outweigh those of the internal factors.