Objective:Mild cognitive impairment(MCI)is characterized by its heterogeneity in pathology, clinical outcomes, and the degree of cognitive impairment.This study aims to identify distinct subtypes of MCI and examine their associated risk of progression to Alzheimer's disease(AD).Methods:Four cognitive domains—memory, language, attention/executive function, and visuospatial ability—were evaluated using seven neuropsychological tests.K-means cluster analysis was employed to categorize MCI into distinct subtypes.Kaplan-Meier survival analysis and Cox regression were utilized to estimate the median survival time and the risk of progression to AD for each subtype, with cognitively normal(CN)individuals at baseline serving as the control group.Only participants with a minimum of two follow-up visits were included in this analysis.Results:A total of 1, 020 subjects with baseline MCI were included in the study, with an age range of 60 to 90 years and a mean age of 73.6 years.Among these subjects, 40.5% were female, and the mean length of education was 16.0 years.The MCI subtypes were classified based on their characteristics as follows: amnestic(n=485), mixed(n=147), and derived normal(n=388).The mixed subtype performed poorly across all neuropsychological tests, particularly demonstrating significantly worse results than the other two subtypes in attention/executive ability and visuospatial functioning.The amnestic subtype primarily exhibited deficits in the memory cognition dimension, while the derived normal subtype scored poorly on the delayed recall aspect of memory cognition.For the survival analysis, a total of 1, 427 subjects were included, with a mean follow-up duration of 50 months.The proportions of subjects who progressed to AD during follow-up were 48.8% for amnestic MCI, 60.0% for mixed MCI, 16.0% for derived normal MCI, and 6.4% for CN individuals at baseline.The mean time to conversion to AD was 29.1 months for amnestic MCI, 19.6 months for mixed MCI, 53.6 months for derived normal MCI, and 85.9 months for CN subjects.There were statistically significant differences in survival time among the subtypes( P<0.001), with the mixed subtype exhibiting the shortest median survival time and the highest risk of progression to AD( HR=20.0, 95% CI: 13.0-30.8).In contrast, the derived normal subtype had the longest survival time and the lowest risk of progression to AD( HR=2.7, 95% CI: 1.7-4.1). Conclusions:MCI subtypes exhibit significant heterogeneity regarding cognitive impairment, progression risk, and time to AD.Individuals with mixed MCI demonstrate the shortest progression time and the highest risk of transitioning to AD.Consequently, early prevention and intervention strategies for AD should prioritize this particular subgroup.

Objective:This study aimed to evaluate the effects of hypertensive disorders of pregnancy (HDP), including their clinical subtypes, on neonatal heel blood methionine levels and explore potential dose-effect relationships.Methods:A retrospective cohort study was conducted among 11 007 singleton pregnancies and their neonates delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from July 2021 to October 2022. Participants were stratified into an HDP group [ n=992; 480 with gestational hypertension, 512 with preeclampsia (including 229 severe cases)] and a non-HDP control group ( n=10 015). Methionine concentrations were measured using tandem mass spectrometry from heel blood dried filter paper samples collected within 72 hours post-delivery. Statistical analyses included non-parametric tests to compare intergroup differences, multiple linear regression to evaluate the effects of HDP on methionine levels, and multivariate logistic regression to identify risk factors for hypermethioninemia (>50 μmol/L). Results:(1) Baseline data: Maternal age was higher in the HDP group compared to controls [33 (30-36) vs. 33 (30-35) years, Z=－2.29, P=0.022], with elevated pre-pregnancy body mass index (BMI) [23 (21-26) vs. 21 (20-23) kg/m2, Z=－17.15, P<0.001] and increased gestational hyperglycemia prevalence [26.5% (263/992) vs. 19.8% (1 986/10 015), χ2=27.95, P<0.001]. (2) Methionine level: Neonates in the HDP group exhibited higher methionine levels [25.96 (21.58-30.89) vs. 24.77 (20.45-29.53) μmol/L, Z=－5.26, P<0.001], with a severity-dependent gradient: gestational hypertension [25.83 (21.77-30.61)], preeclampsia [26.05 (21.23-31.11)], and severe preeclampsia [26.15 (21.25-32.13)] ( Z=2.97, 3.92, 2.26; all P<0.05). Trend analysis confirmed a dose-effect relationship between HDP and neonatal methionine ( χ2=7.82, P=0.005). (3) Multivariate analysis: After adjusting for confounding factors such as maternal age and BMI, HDP remained independently associated with elevated methionine levels ( β=0.93, 95% CI: 0.47-1.40, t=3.92, P<0.001) and increased hypermethioninemia risk ( OR=2.75, 95% CI: 1.13-6.68). Subgroup analysis revealed ORs of 3.20 (95% CI: 1.07-9.57) for gestational hypertension, 3.25 (95% CI: 1.09-9.72) for preeclampsia, and 5.23 (95% CI: 1.54-17.82) for severe preeclampsia (all P<0.05). (4) Neonatal outcomes: Neonates in the HDP group had lower birth weights [3 230 (2 910-3 560) vs. 3 335 (3 070-3 600) g, Z=－7.43, P<0.001] and higher fetal growth restriction rates [10.3% (102/992) vs. 3.1% (306/10 015), χ2=136.47, P<0.001]. Conclusions:HDP demonstrates an elevation of neonatal methionine levels, correlating with disease severity, particularly in severe preeclampsia. These findings underscore the necessity for enhanced metabolic monitoring and long-term follow-up in offspring of mothers with HDP, especially those with severe preeclampsia.

Objective:To investigate the relationship between the early pregnancy triglyceride-glucose (TyG) index and gestational diabetes mellitus (GDM) in twin pregnancies.Methods:This retrospective study involved twin-pregnant women who visited Beijing Obstetrics and Gynecology Hospital, Capital Medical University from October 2015 to February 2021. Based on the results of the 75 g oral glucose tolerance test (OGTT) performed at 24-28 weeks of gestation, the women were divided into the GDM and the control groups. The groups were further stratified based on maternal age (<35 years or ≥35 years), pre-pregnancy body mass index (BMI) (<24.0 or ≥24.0 kg/m2), and conception method [assisted reproductive technology (ART) or natural conception]. The correlation between early pregnancy TyG index and GDM, as well as the predictive value of the early pregnancy TyG index for the risk of GDM in twin pregnancies, were analyzed. The TyG index in early pregnancy was then divided into tertiles, and the risks of GDM in low, medium, and high TyG index groups were analyzed. Statistical analyses were performed using independent sample t-test, non-parametric test, Chi-square test, and binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the early pregnancy TyG index for GDM in twin pregnancies. Results:(1) A total of 1 684 twin-pregnant women were included, with an average age of 32.3 years (29.8-34.9 years) and a pre-pregnancy BMI of 22.0 kg/m2 (20.0-24.3 kg/m2). Among them, 319 (18.9%) were multiparas, 982 (58.3%) conceived through ART, and 357 (21.2%) were monochorionic twins. Of the 1 684 women, 367 (21.8%) were diagnosed with GDM (GDM group), whereas the remaining 1 317 were classified as the control group. (2) Compared to the control group, the GDM group had older maternal age [(32.2±3.7) years vs. (33.3±3.8) years, t=－4.92], higher pre-pregnancy weight, and BMI [57.5 kg (52.0-65.0 kg) vs. 60.0 kg (55.0-67.3 kg), U=279 901.50; 21.8 kg/m2 (19.8-24.0 kg/m2) vs. 22.9 kg/m2 (20.9-25.5 kg/m2), U=288 435.00]. The proportions of a family history of diabetes, history of GDM and polycystic ovary syndrome (PCOS) were all higher in the GDM group compared to the control group [9.6% (127/1 317) vs. 19.1% (70/367), χ 2=24.71; 0.8% (2/1 317) vs. 10.8% (8/367), χ 2=20.00; 9.1% (120/1 317) vs. 15.3% (56/367), χ 2=11.59] (all P<0.001). The GDM group had higher early pregnancy fasting blood glucose, triglyceride, and TyG indices compared to the control group [4.51 mmol/L (4.28-4.75 mmol/L) vs. 4.68 mmol/L (4.42-4.97 mmol/L), U=7.14; 1.23 mmol/L (0.93-1.57 mmol/L) vs. 1.43 mmol/L (1.09-1.89 mmol/L), U=4.81; 8.39±0.41 vs. 8.59±0.43, t=6.46]. The incidence of gestational anemia and weight gain were lower in the GDM group compared to the control group [39.2% (516/1 317) vs. 33.0% (121/367), χ 2=4.71; 17.0 kg (13.7-20.5 kg) vs. 15.0 kg (12.0-18.3 kg), U=187 966.00] (all P<0.05). The proportion of male newborns in the GDM group was higher than in the control group [52.5% (1 384/2 634) vs. 46.7% (343/734), χ 2=7.77, P=0.005]. (3) Early pregnancy TyG index was associated with GDM in twin pregnancies ( OR=3.164, 95% CI: 2.371-4.220, P<0.001). After adjusting for maternal age, pre-pregnancy BMI, history of GDM, history of macrosomia, and family history of diabetes, the early pregnancy TyG index remained associated with GDM ( OR=2.560, 95% CI: 1.884-3.478, P<0.001). Analysis of the early pregnancy TyG index divided into tertiles (corresponding TyG indices of 8.25 and 8.59) revealed that, compared to those with a low TyG index, those with a mid TyG index had a 0.555-fold increased risk of GDM ( OR=1.555, 95% CI: 1.119-2.159, P=0.008), and those with a high TyG index had a 1.564-fold increased risk of GDM ( OR=2.564, 95% CI: 1.836-3.530, P<0.001). Stratified analysis by age, BMI, and mode of conception showed that the early pregnancy TyG index was associated with GDM in twin pregnancies (all P<0.001). (4) The threshold value for the early pregnancy TyG index to predict GDM in twin pregnancies was 8.33, with an area under the curve (AUC) of 0.632, 95% CI: 0.600-0.665, sensitivity of 0.744, and specificity of 0.436. The AUC in twin pregnancies for those who conceived via ART was 0.635 (95% CI: 0.593-0.676, P<0.001), slightly higher than in those who conceived naturally (AUC=0.628, 95% CI: 0.576-0.681, P<0.001). After adjusting for maternal age, pre-pregnancy BMI, history of GDM, and family history of diabetes, the AUC for the early pregnancy TyG index to predict GDM in twin pregnancies was 0.675 (95% CI: 0.644-0.707). For those who conceived via ART, the AUC (95% CI) was 0.675 (0.634-0.717), slightly lower than for those who conceived naturally [0.682 (0.632-0.733)] (all P<0.001). Conclusion:A high TyG index in the first trimester is a risk factor for GDM in twin pregnancies, but its predictive value for GDM in twin pregnancies needs further research to be confirmed.

Objective:To investigate the characteristics of weight gain in the mid and late pregnancy of women with early pregnancy weight loss, and the relationship between weight gain and weight gain rate before the diagnosis of gestational diabetes mellitus (GDM) and GDM.Methods:A retrospective study was conducted on 2 614 singleton pregnant women who underwent prenatal care and delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from January 2014 to December 2021, and whose weight decreased compared to pre-pregnancy weight by 16 weeks of gestation. The rate of weight gain in mid and late pregnancy, also weight gain and weight gain rate at each stage were analyzed. Multivariate logistic regression was used to analyze the impact of total weight gain and weight gain rate at each stage before the diagnosis of GDM on the risk of GDM.Results:The rates of weight gain in mid and late pregnancy for women with early pregnancy weight loss who were underweight, normal weight, overweight, and obese before pregnancy were (0.60±0.15), (0.59±0.18), (0.53±0.20), and (0.42±0.20) kg/week, respectively, all higher than the "Chinese Recommended Standards for Weight Gain During Pregnancy" [which are (0.37-0.56), (0.26-0.48), (0.22-0.37), and (0.15-0.30) kg/week, respectively]. The weight gain rates at each stage of mid and late pregnancy in women with early pregnancy weight loss showed a "bimodal" trend, with the first peak in weight gain rate occurring at 16-20 or 20-24 weeks of gestation [weight gain rates for underweight, normal weight, overweight, and obese women before pregnancy were 0.75 kg/week (0.44-1.00 kg/week), 0.74 kg/week (0.50-1.00 kg/week), 0.63 kg/week (0.39-0.86 kg/week), and 0.50 kg/week (0.25-0.74 kg/week), respectively] and the second peak occurring at 28-32 weeks [weight gain rates for underweight, normal weight, overweight, and obese women before pregnancy were 0.63 kg/week (0.50-1.00 kg/week), 0.63 kg/week (0.38- 0.88 kg/week), 0.60 kg/week (0.25-0.88 kg/week), and 0.50 kg/week (0.22-0.75 kg/week). As of 28 weeks and 36 weeks of gestation, 53.7% (1 404/2 614) and 77.4% (1 946/2 512) of pregnant women, respectively, reached the lower limit of the recommended weight gain for the corresponding gestational weeks. No association was found between insufficient weight gain ( aOR=0.828, 95% CI: 0.639-1.071, P=0.151) or excessive weight gain ( aOR=0.936, 95% CI: 0.598-1.465, P=0.773) before the diagnosis of GDM and the risk of GDM. However, obese women with a weight loss greater than 5% of their pre-pregnancy weight in early pregnancy and a rapid weight gain rate (> P 75) between 16-20 weeks of gestation had an increased risk of developing GDM ( aOR=32.870, 95% CI: 1.625-664.775, P=0.023). Conclusions:In clinical practice, dynamic monitoring of weight changes at various stages of pregnancy in women who lose weight in early pregnancy is recommended. Targeted weight management during mid-pregnancy for women who are obese before pregnancy and experience significant weight loss in early pregnancy may help prevent excessive gestational weight gain and decrease the risk of GDM.

Objective:To investigate the relationship between the early pregnancy triglyceride-glucose (TyG) index and gestational diabetes mellitus (GDM) in twin pregnancies.Methods:This retrospective study involved twin-pregnant women who visited Beijing Obstetrics and Gynecology Hospital, Capital Medical University from October 2015 to February 2021. Based on the results of the 75 g oral glucose tolerance test (OGTT) performed at 24-28 weeks of gestation, the women were divided into the GDM and the control groups. The groups were further stratified based on maternal age (<35 years or ≥35 years), pre-pregnancy body mass index (BMI) (<24.0 or ≥24.0 kg/m2), and conception method [assisted reproductive technology (ART) or natural conception]. The correlation between early pregnancy TyG index and GDM, as well as the predictive value of the early pregnancy TyG index for the risk of GDM in twin pregnancies, were analyzed. The TyG index in early pregnancy was then divided into tertiles, and the risks of GDM in low, medium, and high TyG index groups were analyzed. Statistical analyses were performed using independent sample t-test, non-parametric test, Chi-square test, and binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the early pregnancy TyG index for GDM in twin pregnancies. Results:(1) A total of 1 684 twin-pregnant women were included, with an average age of 32.3 years (29.8-34.9 years) and a pre-pregnancy BMI of 22.0 kg/m2 (20.0-24.3 kg/m2). Among them, 319 (18.9%) were multiparas, 982 (58.3%) conceived through ART, and 357 (21.2%) were monochorionic twins. Of the 1 684 women, 367 (21.8%) were diagnosed with GDM (GDM group), whereas the remaining 1 317 were classified as the control group. (2) Compared to the control group, the GDM group had older maternal age [(32.2±3.7) years vs. (33.3±3.8) years, t=－4.92], higher pre-pregnancy weight, and BMI [57.5 kg (52.0-65.0 kg) vs. 60.0 kg (55.0-67.3 kg), U=279 901.50; 21.8 kg/m2 (19.8-24.0 kg/m2) vs. 22.9 kg/m2 (20.9-25.5 kg/m2), U=288 435.00]. The proportions of a family history of diabetes, history of GDM and polycystic ovary syndrome (PCOS) were all higher in the GDM group compared to the control group [9.6% (127/1 317) vs. 19.1% (70/367), χ 2=24.71; 0.8% (2/1 317) vs. 10.8% (8/367), χ 2=20.00; 9.1% (120/1 317) vs. 15.3% (56/367), χ 2=11.59] (all P<0.001). The GDM group had higher early pregnancy fasting blood glucose, triglyceride, and TyG indices compared to the control group [4.51 mmol/L (4.28-4.75 mmol/L) vs. 4.68 mmol/L (4.42-4.97 mmol/L), U=7.14; 1.23 mmol/L (0.93-1.57 mmol/L) vs. 1.43 mmol/L (1.09-1.89 mmol/L), U=4.81; 8.39±0.41 vs. 8.59±0.43, t=6.46]. The incidence of gestational anemia and weight gain were lower in the GDM group compared to the control group [39.2% (516/1 317) vs. 33.0% (121/367), χ 2=4.71; 17.0 kg (13.7-20.5 kg) vs. 15.0 kg (12.0-18.3 kg), U=187 966.00] (all P<0.05). The proportion of male newborns in the GDM group was higher than in the control group [52.5% (1 384/2 634) vs. 46.7% (343/734), χ 2=7.77, P=0.005]. (3) Early pregnancy TyG index was associated with GDM in twin pregnancies ( OR=3.164, 95% CI: 2.371-4.220, P<0.001). After adjusting for maternal age, pre-pregnancy BMI, history of GDM, history of macrosomia, and family history of diabetes, the early pregnancy TyG index remained associated with GDM ( OR=2.560, 95% CI: 1.884-3.478, P<0.001). Analysis of the early pregnancy TyG index divided into tertiles (corresponding TyG indices of 8.25 and 8.59) revealed that, compared to those with a low TyG index, those with a mid TyG index had a 0.555-fold increased risk of GDM ( OR=1.555, 95% CI: 1.119-2.159, P=0.008), and those with a high TyG index had a 1.564-fold increased risk of GDM ( OR=2.564, 95% CI: 1.836-3.530, P<0.001). Stratified analysis by age, BMI, and mode of conception showed that the early pregnancy TyG index was associated with GDM in twin pregnancies (all P<0.001). (4) The threshold value for the early pregnancy TyG index to predict GDM in twin pregnancies was 8.33, with an area under the curve (AUC) of 0.632, 95% CI: 0.600-0.665, sensitivity of 0.744, and specificity of 0.436. The AUC in twin pregnancies for those who conceived via ART was 0.635 (95% CI: 0.593-0.676, P<0.001), slightly higher than in those who conceived naturally (AUC=0.628, 95% CI: 0.576-0.681, P<0.001). After adjusting for maternal age, pre-pregnancy BMI, history of GDM, and family history of diabetes, the AUC for the early pregnancy TyG index to predict GDM in twin pregnancies was 0.675 (95% CI: 0.644-0.707). For those who conceived via ART, the AUC (95% CI) was 0.675 (0.634-0.717), slightly lower than for those who conceived naturally [0.682 (0.632-0.733)] (all P<0.001). Conclusion:A high TyG index in the first trimester is a risk factor for GDM in twin pregnancies, but its predictive value for GDM in twin pregnancies needs further research to be confirmed.

Objective:To investigate the characteristics of weight gain in the mid and late pregnancy of women with early pregnancy weight loss, and the relationship between weight gain and weight gain rate before the diagnosis of gestational diabetes mellitus (GDM) and GDM.Methods:A retrospective study was conducted on 2 614 singleton pregnant women who underwent prenatal care and delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from January 2014 to December 2021, and whose weight decreased compared to pre-pregnancy weight by 16 weeks of gestation. The rate of weight gain in mid and late pregnancy, also weight gain and weight gain rate at each stage were analyzed. Multivariate logistic regression was used to analyze the impact of total weight gain and weight gain rate at each stage before the diagnosis of GDM on the risk of GDM.Results:The rates of weight gain in mid and late pregnancy for women with early pregnancy weight loss who were underweight, normal weight, overweight, and obese before pregnancy were (0.60±0.15), (0.59±0.18), (0.53±0.20), and (0.42±0.20) kg/week, respectively, all higher than the "Chinese Recommended Standards for Weight Gain During Pregnancy" [which are (0.37-0.56), (0.26-0.48), (0.22-0.37), and (0.15-0.30) kg/week, respectively]. The weight gain rates at each stage of mid and late pregnancy in women with early pregnancy weight loss showed a "bimodal" trend, with the first peak in weight gain rate occurring at 16-20 or 20-24 weeks of gestation [weight gain rates for underweight, normal weight, overweight, and obese women before pregnancy were 0.75 kg/week (0.44-1.00 kg/week), 0.74 kg/week (0.50-1.00 kg/week), 0.63 kg/week (0.39-0.86 kg/week), and 0.50 kg/week (0.25-0.74 kg/week), respectively] and the second peak occurring at 28-32 weeks [weight gain rates for underweight, normal weight, overweight, and obese women before pregnancy were 0.63 kg/week (0.50-1.00 kg/week), 0.63 kg/week (0.38- 0.88 kg/week), 0.60 kg/week (0.25-0.88 kg/week), and 0.50 kg/week (0.22-0.75 kg/week). As of 28 weeks and 36 weeks of gestation, 53.7% (1 404/2 614) and 77.4% (1 946/2 512) of pregnant women, respectively, reached the lower limit of the recommended weight gain for the corresponding gestational weeks. No association was found between insufficient weight gain ( aOR=0.828, 95% CI: 0.639-1.071, P=0.151) or excessive weight gain ( aOR=0.936, 95% CI: 0.598-1.465, P=0.773) before the diagnosis of GDM and the risk of GDM. However, obese women with a weight loss greater than 5% of their pre-pregnancy weight in early pregnancy and a rapid weight gain rate (> P 75) between 16-20 weeks of gestation had an increased risk of developing GDM ( aOR=32.870, 95% CI: 1.625-664.775, P=0.023). Conclusions:In clinical practice, dynamic monitoring of weight changes at various stages of pregnancy in women who lose weight in early pregnancy is recommended. Targeted weight management during mid-pregnancy for women who are obese before pregnancy and experience significant weight loss in early pregnancy may help prevent excessive gestational weight gain and decrease the risk of GDM.

Objective:Mild cognitive impairment(MCI)is characterized by its heterogeneity in pathology, clinical outcomes, and the degree of cognitive impairment.This study aims to identify distinct subtypes of MCI and examine their associated risk of progression to Alzheimer's disease(AD).Methods:Four cognitive domains—memory, language, attention/executive function, and visuospatial ability—were evaluated using seven neuropsychological tests.K-means cluster analysis was employed to categorize MCI into distinct subtypes.Kaplan-Meier survival analysis and Cox regression were utilized to estimate the median survival time and the risk of progression to AD for each subtype, with cognitively normal(CN)individuals at baseline serving as the control group.Only participants with a minimum of two follow-up visits were included in this analysis.Results:A total of 1, 020 subjects with baseline MCI were included in the study, with an age range of 60 to 90 years and a mean age of 73.6 years.Among these subjects, 40.5% were female, and the mean length of education was 16.0 years.The MCI subtypes were classified based on their characteristics as follows: amnestic(n=485), mixed(n=147), and derived normal(n=388).The mixed subtype performed poorly across all neuropsychological tests, particularly demonstrating significantly worse results than the other two subtypes in attention/executive ability and visuospatial functioning.The amnestic subtype primarily exhibited deficits in the memory cognition dimension, while the derived normal subtype scored poorly on the delayed recall aspect of memory cognition.For the survival analysis, a total of 1, 427 subjects were included, with a mean follow-up duration of 50 months.The proportions of subjects who progressed to AD during follow-up were 48.8% for amnestic MCI, 60.0% for mixed MCI, 16.0% for derived normal MCI, and 6.4% for CN individuals at baseline.The mean time to conversion to AD was 29.1 months for amnestic MCI, 19.6 months for mixed MCI, 53.6 months for derived normal MCI, and 85.9 months for CN subjects.There were statistically significant differences in survival time among the subtypes( P<0.001), with the mixed subtype exhibiting the shortest median survival time and the highest risk of progression to AD( HR=20.0, 95% CI: 13.0-30.8).In contrast, the derived normal subtype had the longest survival time and the lowest risk of progression to AD( HR=2.7, 95% CI: 1.7-4.1). Conclusions:MCI subtypes exhibit significant heterogeneity regarding cognitive impairment, progression risk, and time to AD.Individuals with mixed MCI demonstrate the shortest progression time and the highest risk of transitioning to AD.Consequently, early prevention and intervention strategies for AD should prioritize this particular subgroup.

Objective:This study aimed to evaluate the effects of hypertensive disorders of pregnancy (HDP), including their clinical subtypes, on neonatal heel blood methionine levels and explore potential dose-effect relationships.Methods:A retrospective cohort study was conducted among 11 007 singleton pregnancies and their neonates delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from July 2021 to October 2022. Participants were stratified into an HDP group [ n=992; 480 with gestational hypertension, 512 with preeclampsia (including 229 severe cases)] and a non-HDP control group ( n=10 015). Methionine concentrations were measured using tandem mass spectrometry from heel blood dried filter paper samples collected within 72 hours post-delivery. Statistical analyses included non-parametric tests to compare intergroup differences, multiple linear regression to evaluate the effects of HDP on methionine levels, and multivariate logistic regression to identify risk factors for hypermethioninemia (>50 μmol/L). Results:(1) Baseline data: Maternal age was higher in the HDP group compared to controls [33 (30-36) vs. 33 (30-35) years, Z=－2.29, P=0.022], with elevated pre-pregnancy body mass index (BMI) [23 (21-26) vs. 21 (20-23) kg/m2, Z=－17.15, P<0.001] and increased gestational hyperglycemia prevalence [26.5% (263/992) vs. 19.8% (1 986/10 015), χ2=27.95, P<0.001]. (2) Methionine level: Neonates in the HDP group exhibited higher methionine levels [25.96 (21.58-30.89) vs. 24.77 (20.45-29.53) μmol/L, Z=－5.26, P<0.001], with a severity-dependent gradient: gestational hypertension [25.83 (21.77-30.61)], preeclampsia [26.05 (21.23-31.11)], and severe preeclampsia [26.15 (21.25-32.13)] ( Z=2.97, 3.92, 2.26; all P<0.05). Trend analysis confirmed a dose-effect relationship between HDP and neonatal methionine ( χ2=7.82, P=0.005). (3) Multivariate analysis: After adjusting for confounding factors such as maternal age and BMI, HDP remained independently associated with elevated methionine levels ( β=0.93, 95% CI: 0.47-1.40, t=3.92, P<0.001) and increased hypermethioninemia risk ( OR=2.75, 95% CI: 1.13-6.68). Subgroup analysis revealed ORs of 3.20 (95% CI: 1.07-9.57) for gestational hypertension, 3.25 (95% CI: 1.09-9.72) for preeclampsia, and 5.23 (95% CI: 1.54-17.82) for severe preeclampsia (all P<0.05). (4) Neonatal outcomes: Neonates in the HDP group had lower birth weights [3 230 (2 910-3 560) vs. 3 335 (3 070-3 600) g, Z=－7.43, P<0.001] and higher fetal growth restriction rates [10.3% (102/992) vs. 3.1% (306/10 015), χ2=136.47, P<0.001]. Conclusions:HDP demonstrates an elevation of neonatal methionine levels, correlating with disease severity, particularly in severe preeclampsia. These findings underscore the necessity for enhanced metabolic monitoring and long-term follow-up in offspring of mothers with HDP, especially those with severe preeclampsia.

Mild cognitive impairment(MCI)is a prodromal phase of dementia with heterogeneity in etiology, clinical presentation, disease progression, outcome, and prognosis.The number of studies on MCI subtypes is increasing each year.This article discussed the subtypes of MCI from the perspectives of phenotypic characteristics, etiology, progression, outcome, and data-driven approaches, and further summarizes the epidemiological characteristics, influencing factors, and risk of progression to dementia of each subtype.Despite the increasing number of studies on MCI subtyping, research remains limited on the correlation between MCI subtypes from different perspectives, indicating a need for further investigation in order to achieve more accurate and effective diagnosis and treatment of MCI and obtain evidence for dementia prevention.