Marital History and Cognition in a Chinese Longevity Cohort.

Background: Marital factor has been associated with dementia and Alzheimer's disease, but there is limited evidence on the impact of holistic marital history over time. Objective: This study aimed to examine association of marital history with cognition. Methods: The study included 24,596 dementia-free participants from the Chinese Longitudinal Healthy Longevity Study (CLHLS). Holistic marital history was collected at baseline, categorizing participants into five groups: widow-single, widow-remarried, divorce-single, divorce-remarried and married based on the first two marriages. Dementia was collected at follow-up through self-report or from a delegate if the participant was deceased. For 15,355 participants, the Chinese Mini-Mental Status Examination (CMMSE) was administered at both baseline and follow-ups. Cognitive impairment was defined as a follow-up CMMSE score below 18, and rate of cognitive change was calculated as the change in CMMSE score between consecutive visits divided by the duration. Results: Compared with married older adults, widow-single group had significantly higher risk of dementia (HR 1.28, 95% CI 1.05, 1.54), cognitive impairment (HR 1.31, 95% CI 1.17, 1.47) and significantly faster decline of MMSE score (ß -0.09, 95% CI -0.17, -0.01). Meanwhile, widow-remarried group had significantly lower risk of dementia, cognitive impairment and slower MMSE score decline than widow-single group, although the differences were only significant among female but not male. Conclusions: In this prospective cohort, married older adults and those widowed but with a second marriage had significantly better cognition than widowed individuals who did not remarry.

Association of a healthy ageing index with health-related outcomes in a multi-ethnic cohort from Singapore.

BACKGROUND: The global population is ageing rapidly and it is important to promote healthy ageing. The Healthy Ageing Index (HAI) is a comprehensive measure of health, but there is limited research on its association with other age-related outcomes. The management of an aging population necessitates considerations even among generally healthy adults, as age-related diseases often remain unaccounted for until later stages of life. This study explores the association of risk factors with HAI and its association with peripheral artery disease (PAD), muscle strength, health-related quality of life (HRQoL), and psychological distress in the Singapore Multi-Ethnic Cohort study. METHODS: This cross-sectional study involved 1909 participants (median (Q1, Q3) age: 53 (48, 60) years and 59.3% females) from Singapore Multi-Ethnic Cohort study. The risk factors of HAI included age, gender, ethnicity, education level, smoking, alcohol consumption, employment, BMI and past medical histories. PAD was assessed using ankle-brachial index (ABI), handgrip strength (HGS), HRQoL with the EQ-5D-5 L questionnaire and psychological distress via the Kessler Psychological Distress Scale (K10). HAI components were assessed using relevant marker tests. RESULTS: Older age, Malay and Indian ethnicities, unemployment, high BMI and histories of CHD, hypercholesterolaemia, tumours and TIA/stroke were associated with lower HAI scores indicative of poorer health. Higher HAI scores were associated with females and higher education levels. Lower HAI scores were significantly associated with low ABI, high K10 scores, mobility and anxiety/depression dimensions of EQ-5D-5 L. CONCLUSION: The most important factors associated with HAI were age, sex, ethnicity, education, unemployment, BMI and a history of health conditions. Lower HAI scores were significantly associated with PAD, lower HRQoL and psychological distress. Thus, the HAI demonstrates promise as an evaluation method for assessing PAD, overall muscle strength and HRQoL in a population-based setting.

Loss of white matter integrity mediates the association between cortical cerebral microinfarcts and cognitive dysfunction: A longitudinal study.

Cortical cerebral microinfarcts (CMIs) are associated with loss of white matter (WM) integrity and cognitive impairment in cross-sectional studies, while further investigation using longitudinal datasets is required. This study aims to establish the association between cortical CMIs and WM integrity assessed by diffusion-tensor imaging (DTI) measures and to investigate whether DTI measures mediate the relationship between cortical CMIs and cognitive decline. Cortical CMIs were graded on 3T MRI. DTI measures were derived from histogram analysis of mean diffusivity (MD) and fractional anisotropy (FA). Cognitive function was assessed using a neuropsychological test battery. Linear mixed-effect models were employed to examine associations of cortical CMIs with longitudinal changes in DTI measures and cognitive function. Final analysis included 231 patients (71.14 ± 7.60 years). Presence of cortical CMIs at baseline was associated with longitudinal changes in MD median and peak height and FA median and peak height, as well as global cognition (ß = -0.50, 95%CI: -0.91, -0.09) and executive function (ß = -0.77, 95%CI: -1.25, -0.28). MD median mediated the cross-sectional association between cortical CMIs and global cognition. Further studies are required to investigate whether cortical CMIs and loss of WM integrity are causally related or if they are parallel mechanisms that contribute to cognitive decline.

Association between Marital Status and Cognitive Impairment in a Multi-Ethnic Asian Population.

OBJECTIVE: This study aims to examine the potential factors associated with marital status and determine the association between marital status and cognitive impairment in a multi-ethnic Asian population. METHOD: This study included 2321 participants from Singapore Multi-Ethnic Cohort revisit study (aged 40-89). Participants were classified into married and unmarried group at baseline and follow-up according to self-reported marital status. Mini-Mental Status Examination (MMSE) was administered, and cognitive impairment was defined as a MMSE <26. We conducted both cross-sectional and longitudinal analyses to examine the association of marital status at one time point as well as marital transition with cognitive impairment. RESULTS: Of the 2321 participants, a total of 1914 (82.5%) were married. The factors associated with marital status included younger age, male sex, higher household income, higher education, and higher physical activity levels. Additionally, married participants also had higher alternative healthy eating index (AHEI-2010) scores, and a lower burden of hypertension and diabetes. Among those who were married, the median (Q1, Q3) MMSE score was 29 (28,30) while those who were unmarried was 29 (27, 30) (p <0.01). Participants who had never been married had the highest odds of cognitive impairment compared to their married counterparts (Model III: OR=1.48, 95% CI: 1.03, 2.14). Older age (p-interaction value=0.003) and Indian ethnicity (p-interaction value=0.028) further strengthened these associations. CONCLUSION: Marriage was associated with lower odds of cognitive impairment. Marriage provides social support, companionship, and engagement in mentally stimulating activities contributing to better cognitive health. By identifying risk factors such as marital status, interventions and support systems can be developed to promote healthy cognitive aging.

Association of diet quality with hand grip strength weakness and asymmetry in a multi-ethnic Asian cohort.

Hand grip strength (HGS) is an important diagnostic tool for sarcopenia and a reliable predictor for age-related chronic diseases and mortality. Interventions in nutrition have been shown as a low-cost strategy to maintain muscular strength and mass. However, there are limited data on the effect of diet on HGS in Southeast Asian populations. This study aims to investigate the association of diet quality with HGS weakness and asymmetry in a multi-ethnic population in Singapore. This cross-sectional study used data from the Singapore Multi-Ethnic Cohort (n = 1547). Dietary data were collected using a validated semi-quantitative FFQ and summarised as the Dietary Quality Index - International (DQI-I). HGS was calculated as the maximum value of six measurements from both hands. HGS weakness and asymmetry were defined using well-recognised criteria. Multivariable linear regression and logistic regression were utilised for continuous and binary outcomes, respectively, adjusting for age, sex, ethnicity, physical activity and smoking status. It was found that the highest quartile of DQI-I was significantly associated with higher HGS (ß = 1·11; 95 % CI 0·41, 1·82; Pfor trend < 0·001) and lower odds of HGS asymmetry (OR = 0·71; 95 % CI 0·53, 0·94; Pfor trend = 0·035) and both HGS weakness and asymmetry (OR = 0·50; 95 % CI 0·32, 0·76; Pfor trend = 0·004). Among the different components of DQI-I, only dietary adequacy was significantly associated with higher HGS (Pfor trend < 0·001) and lower odds for both HGS weakness and asymmetry (Pfor trend = 0·006). Our findings support that DQI-I, an indicator of overall diet quality, can be used to provide dietary guidelines for prevention and management of muscle wasting, sarcopenia and frailty.

Trajectory of stratum corneum lipid subclasses in the first year of life and associations with atopic dermatitis: A prospective cohort study.

BACKGROUND: Trajectories of stratum corneum (SC) lipid subclasses and their associations with infant atopic dermatitis (AD) are unclear. This study aimed to quantify the trajectories of 15 SC subclasses and carbon chain lengths and their associations with AD within 12 months. METHODS: In total, 213 newborns were enrolled at birth with nonlesional skin samples collected from the inner forearm at birth, 42 days, 3, 6, and 12 months, respectively. Lesional skin samples were collected from 120 AD patients at clinic with the disease onset within the first year of life. Mass spectrometry was applied to assess relative contents of 12 ceramide (CER), three free fatty acid (FFA) subclasses, and average carbon chain length (CCL). AD incident within 1 year old was diagnosed by dermatologists according to UK criteria. RESULTS: Sixty-four (30.0%) cases of ADs occurred in the cohort. All SC lipid subclasses and CCLs, but EOP varied significantly during the first year. AD infants showed lower NP but higher NS, NH, AP, hydroxy FFA, and CCL of FFAs compared with nonaffected infants. After normalization by age, the differences remained and were more pronounced in lesional skin of clinical AD infants compared with non-ADs. NS, NH, and CCL of FFAs in lesional skin of AD infants showed positive and significant correlations with the levels of transepidermal water loss at 3 month; some evidence supports a negative correlation for NP. CONCLUSIONS: We provide an overview of developmental trajectories of 15 CER and FFA subclasses across the first year of healthy infants and a link between the imbalance of some subclasses with the development of AD.

Association of physical activity with dementia and cognitive decline in UK Biobank.

INTRODUCTION: There is a lack of studies on the association between specific physical activity (PA) types and dementia. We examined the association of leisure time physical activity (LTPA), occupational physical activity (OPA), and sedentary lifestyle with dementia risk and cognitive decline using the UK-Biobank study. METHODS: Baseline PA was collected using questionnaires. A total of 502,481 dementia-free participants were recruited in 2006-2010 and followed for 10 years until the end of 2020 for the ascertainment of dementia. Associations of PA with incident dementia and cognitive decline were examined. RESULTS: Higher levels of LTPA and OPA and lower levels of sedentary hours were associated with lower dementia risk. The fifth quintiles of LTPA (hazard ratio [HR] = 0.53, 95% confidence interval [CI]: 0.43-0.67) and OPA (HR = 0.68, 95% CI:0.51-0.90) had lower dementia risk, whereas the fifth quintile of sedentary lifestyle had higher dementia risk (HR = 1.23, 95% CI:1.08-1.41). DISCUSSION: Our findings suggest the promotion of an active lifestyle suggested to be preventive of dementia risk. This research has been conducted using the UK Biobank Resource under Application Number 71022.

Modified lung ultrasound score for bronchopulmonary dysplasia predicts late respiratory outcomes in preterm infants.

OBJECTIVE: Lung ultrasound (LUS) is a useful and radiation-free diagnostic tool for predicting bronchopulmonary dysplasia, which is a risk factor for late respiratory disease. However, data on the relationship of LUS with late respiratory disease was scarce. This study aims to determine whether LUS is associated with late respiratory disease during early childhood. METHODS: This prospective cohort study enrolled preterm infants born before 32 weeks of gestation. LUS was performed at 36 weeks' postmenstrual age. The predictive values of a modified lung ultrasound (mLUS) score based on eight standard sections were assessed to predict late respiratory disease, defined as a physician diagnosis of bronchopulmonary dysplasia deterioration, asthma, reactive airway disease, bronchiolitis, pneumonia, or respiratory-related hospitalization during the first 2 years of life. RESULTS: A total of 94 infants completed follow-up, of whom 74.5% met the late respiratory disease criteria. The mLUS scores were significantly associated with late respiratory disease (adjusted odds ratio: 1.23, CI: 1.10-1.38, p < 0.001). The mLUS scores also well predicted late respiratory disease (AUC = 0.820, 95% CI: 0.733-0.907). These scores were superior to the classic lung ultrasound score (p = 0.02) and as accurate as the modified NICHD-defined bronchopulmonary dysplasia classification (p = 0.91). A mLUS score ≥14 was the optimal cutoff point for predicting late respiratory disease. CONCLUSION: The modified lung ultrasound score correlates significantly with late respiratory disease and well predicts it in preterm infants during the first 2 years of life.

Association between nutrition and cognition in a multi-ethnic cohort from Singapore.

BACKGROUND: Nutrition, a modifiable risk factor, presents a low-cost prevention strategy to reduce the burden of cognitive impairment and dementia. However, studies examining the effects of dietary patterns on cognition are lacking in multi-ethnic Asian populations. We investigate the association between diet quality, measured with the Alternative Healthy Eating Index (AHEI)-2010, and cognitive impairment in middle-aged and older adults of different ethnicities (Chinese, Malay, Indian) in Singapore. METHODS: This cross-sectional study (n = 3138; mean age: 50.4 ± 9.8, 58.4% women) was based on data from the Singapore Multi-Ethnic Cohort. Dietary intake collected with a validated semi-quantitative Food Frequency Questionnaire was converted into AHEI-2010 scores. Cognition, assessed with the Mini-Mental State Examination (MMSE), was analysed as a continuous or binary outcome (cognitively impaired or not, using cut-offs of ≥ 24, 26 or 28 for no education, primary school education and secondary school education and above). Multivariable linear and logistic regression models were used to examine associations between AHEI-2010 and cognition, adjusting for covariates. RESULTS: A total of 988 (31.5%) participants had cognitive impairment. Higher AHEI-2010 scores were significantly associated with higher MMSE scores [ß = 0.44; 95% confidence interval (CI) 0.22-0.67 highest vs. lowest quartile; p-trend < 0.001] and lower odds of cognitive impairment [OR 0.69; 95% CI 0.54-0.88; p-trend = 0.01] after adjusting for all the covariates. No significant associations were observed for individual dietary components of the AHEI-2010 with MMSE or cognitive impairment. CONCLUSION: Healthier dietary patterns were associated with better cognitive function in middle-aged and older Singaporeans. These findings could inform better support to promote healthier dietary patterns in Asian populations.

Association between Shift Work Schedules and Cardiovascular Events in a Multi-Ethnic Cohort.

BACKGROUND: Shift work is known to increase the risk of cardiometabolic diseases and mortality. We investigate the relationship between shift work schedules and cardiometabolic risk factors (smoking, hypertension, and obesity) and their association with cardiometabolic diseases (diabetes and cardiovascular diseases) in a multi-ethnic population from Singapore. METHODS: 2469 participants from the Singapore-based Multi-Ethnic Cohort underwent physical and clinical assessments. Shift work schedules (morning, evening, night, and mixed) were assessed using a validated questionnaire. RESULTS: Among shift workers, night shift workers had a significantly higher prevalence of smoking (54.5%), diabetes (27.3%), and cardiovascular events (14.1%). Compared to non-shift workers, workers in the night (OR = 2.10, 95%CI: 1.26-3.41) and mixed (OR = 1.74, 95%CI: 1.22-2.48) shift groups were more likely to be current smokers. A significant association between shift duration and smoking (OR = 1.02, 95%CI: 1.00-1.03) was also observed, with longer shift duration (in years) leading to an increase in smoking behavior. No significant associations were found between shift work schedules and hypertension, obesity (BMI), diabetes, and cardiovascular disease, as well as other cardiometabolic risk factors and diseases. CONCLUSION: This study found that shift schedules and shift duration were most strongly associated with smoking status after covariate adjustments (age, gender, ethnicity, socioeconomic status, and work arrangement), with night and mixed shift types being strongly associated with current smoker status. As smoking is a modifiable risk factor for cardiometabolic disease, employers of shift workers should increase work-based health interventions to control smoking and promote a healthier workforce.

Handgrip Strength and Cognitive Performance in a Multiethnic Cohort in Singapore.

BACKGROUND: Handgrip strength (HGS) is an important marker of frailty but there is limited research on lifestyle and vascular determinants of HGS and its relationship with cognitive impairment. OBJECTIVE: To identify determinants of HGS and the association of HGS with cognitive impairment in a multiethnic cohort from Singapore. METHODS: This study (n = 2,109, median [Q1, Q3] age: 53 [48, 60] years, 59.6% women) was based on cross-sectional data from Singapore Multi-Ethnic Cohort. HGS was collected using hand-held Electronic Dynamometer. The potential determinants of HGS included age, sex, ethnicity, smoking, physical activity, serum cholesterol and history of hypertension, diabetes, and stroke. Cognition, assessed with the Mini-Mental State Examination (MMSE), was analyzed as both continuous and binary outcome (cognitively impaired [scores < 26] and cognitively normal [scores≥26]). RESULTS: In total, 239 (11.3%) participants were cognitively impaired. Older age, female sex, Malay or Indian compared with Chinese ethnicity, and diabetes history were associated with decreased HGS, whereas higher education, higher body mass index, and more physical activity were associated with higher HGS. Higher HGS was associated with higher MMSE scores (ß: 0.34, 95% CI: 0.20, 0.49) and 37% lower odds of cognitive impairment (OR: 0.63, 95% CI: 0.49-0.82). These associations were significantly stronger in participants who were older (50-90 years), female, of Malay and Indian ethnicity (compared with Chinese), and less educated. CONCLUSION: In this multi-ethnic Asian population, demographics, vascular risk factors, and lifestyle behaviors were associated with HGS. Additionally, higher HGS was associated with substantially better cognitive function, which association was modified by age, sex, ethnicity, and education level.

Periconception Red Blood Cell Folate and Offspring Congenital Heart Disease : Nested Case-Control and Mendelian Randomization Studies.

BACKGROUND: Periconception folic acid supplementation has been suggested to protect against congenital heart disease (CHD), but the association between maternal red blood cell (RBC) folate, the gold-standard biomarker of folate exposure, and subsequent offspring CHD risk is lacking. OBJECTIVE: To quantify the association between periconception maternal RBC folate and offspring CHD risk. DESIGN: Prospective, nested, case-control study and 1-sample Mendelian randomization. (ClinicalTrials.gov: NCT02737644). SETTING: 29 maternity institutions in 12 districts of Greater Shanghai, China. PARTICIPANTS: All 197 mothers of offspring with CHD and 788 individually matched mothers of unaffected offspring from the SPCC (Shanghai Preconception Cohort). MEASUREMENTS: Maternal RBC folate was measured before or at early pregnancy. Odds ratios [ORs] were estimated using conditional logistic regression after adjustment for covariates. Mendelian randomization was done using the methylenetetrahydrofolate reductase (MTHFR) C677T as the genetic instrument. RESULTS: Case patients had lower median maternal RBC folate concentrations than control participants (714 nmol/L [interquartile range, 482 to 1008 nmol/L] vs. 788 nmol/L [557 to 1094 nmol/L]). Maternal RBC folate concentrations were inversely associated with offspring CHD (adjusted OR per 100 nmol/L, 0.93 [95% CI, 0.89 to 0.99]). The adjusted OR for mothers with periconception RBC folate of 906 nmol/L or more (vs. <906 nmol/L) was 0.61 (CI, 0.40 to 0.93). Mendelian randomization showed that each 100-nmol increase in maternal RBC folate concentrations was significantly associated with reduced offspring CHD risk (OR, 0.75 [CI, 0.61 to 0.92]). LIMITATION: Potential confounding due to unmeasured covariates in the nested case-control study. CONCLUSION: Higher maternal RBC folate is associated with reduced offspring CHD risk. For primary CHD prevention, higher target RBC folate levels than currently recommended for neural tube defect prevention may be needed and warrant further study. PRIMARY FUNDING SOURCE: National Key Research and Development Program of China, National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.

Gender Specificity and Local Socioeconomic Influence on Association of GHR fl/d3 Polymorphism With Growth and Metabolism in Children and Adolescents.

Objective: Growth hormone receptor (GHR) mediates most GH biological actions. This study is aimed to evaluate whether GHR fl/d3 polymorphism contributes to the inter-individual variability of growth and metabolism in healthy children and adolescents. Methods: A total of 4,730 students aged 6-16 years from Yixing and Suqian City in China were included in this cross-sectional study. Height and body mass index (BMI) were transformed into the form of z-score corresponding to age and gender. Logistic regression was used to evaluate the associations of GHR fl/d3 polymorphism with height, BMI, metabolic traits, and hypertension by estimating the odds ratios (ORs) and 95% confidence intervals (CIs). Results: GHR d3 allele was inversely associated with overweight, total cholesterol (TC) and triglyceride (TG) levels (OR [95% CI] for overweight: 0.754 [0.593-0.959], P = 0.021; OR [95% CI] for TC: 0.744 [0.614-0.902], P = 0.003; OR [95% CI] for TG: 0.812 [0.654-0.998], P = 0.047). GHR d3 allele was associated with decreased odds of pre-hypertension in boys (OR [95% CI]: 0.791 [0.645-0.971], P = 0.025), but associated with increased odds of pre-hypertension and hypertension in girls (ORs [95% CIs]: 1.379 [1.106-1.719], P = 0.004; OR [95% CI]: 1.240 [1.013-1.519], P = 0.037). Interaction of GHR fl/d3 polymorphism with gender contributed to increased odds of pre-hypertension and hypertension (interactive ORs [95% CIs]: 1.735 [1.214-2.481], P = 0.003; OR [95% CI]: 1.509 [1.092-2.086], P = 0.013). Stratification analysis showed that the correlation tendencies of GHR fl/d3 polymorphism and BMI with age were different between two cities with discrepant economic development levels. Conclusion: GHR fl/d3 polymorphism is associated with growth, metabolism, and hypertension in children and adolescents with the gender specificity, and the genetic effect of GHR fl/d3 may be modified by the local socioeconomic levels.

A modified lung ultrasound score to evaluate short-term clinical outcomes of bronchopulmonary dysplasia.

BACKGROUND: Lung ultrasound (LUS) is a useful tool for assessing the severity of lung disease, without radiation exposure. However, there is little data on the practicality of LUS in assessing the severity of bronchopulmonary dysplasia (BPD) and evaluating short-term clinical outcomes. We adapted a LUS score to evaluate BPD severity and assess the reliability of mLUS score correlated with short-term clinical outcomes. METHODS: Prospective diagnostic accuracy study was designed to enroll preterm infants with gestational age < 34 weeks. Lung ultrasonography was performed at 36 weeks postmenstrual age. The diagnostic and predictive values of new modified lung ultrasound (mLUS) scores based on eight standard sections were compared with classic lung ultrasound (cLUS) scores. RESULTS: A total of 128 infants were enrolled in this cohort, including 30 without BPD; 31 with mild BPD; 23 with moderate BPD and 44 with severe BPD. The mLUS score was significantly correlated with the short-term clinical outcomes, superior to cLUS score. The mLUS score well correlated with moderate and severe BPD (AUC = 0.813, 95% CI 0.739-0.888) and severe BPD (AUC = 0.801, 95% CI 0.728-0.875), which were superior to cLUS score. The ROC analysis of mLUS score to evaluate the other short-term outcomes also showed significant superiority to cLUS score. The optimal cutoff points for mLUS score were 14 for moderate and severe BPD and 16 for severe BPD. CONCLUSIONS: The mLUS score correlates significantly with short-term clinical outcomes and well evaluates these outcomes in preterm infants.

Comparison of Efficacy of Acupuncture-Related Therapy in the Treatment of Rheumatoid Arthritis: A Network Meta-Analysis of Randomized Controlled Trials.

Background: The refractory, repetitive, and disabling characteristic of rheumatoid arthritis (RA) has seriously influenced the patients' quality of life, and makes it a major public health problem. As a classic complementary and alternative therapy, acupuncture is usually applied for RA combined with disease-modifying anti-rheumatic drugs (DMARDs). However, there are various types of acupuncture, and the curative effects are different in different acupuncture therapies. In this study, we evaluated the clinical efficacy of different acupuncture therapies combined with DMARDs in the treatment of RA. Methods: The randomized controlled trials (RCTs) of acupuncture combined with DMARDs in the treatment of RA were searched in both English and Chinese database of PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, VIP database, Wanfang, and SinoMED, up to October 2021. Literature screening, data extraction, and evaluation of the risk of bias were carried out independently by two researchers, and the data were analyzed by Stata14.2 and GeMTC 0.14.3 software. Results: A total of 32 RCTs were included, including 2,115 RA patients. The results of network meta-analysis were as follows: in terms of improving DAS28 score, Electro-acupuncture + DMARDs has the best efficacy. In terms of improving VAS score, Fire Needle + DMARDs showed the best efficacy. In terms of improving morning stiffness time, acupuncture-related therapies combined with DMARDs were not better than DMARDs alone in improving morning stiffness time in RA patients. In terms of reducing CRP and ESR, Fire Needle + DMARDs showed the best efficacy. In terms of reducing RF, Moxibustion + DMARDs has the best efficacy. Conclusions: The comprehensive comparison of the outcome indicators in 8 different treatments indicates that electro-acupuncture combined with DMARDs is the best combined therapy in improving DAS28 score, while in terms of improving pain and serological markers, fire needle combined with DMARDs and moxibustion combined with DMARDs were the best combined therapies. However, it is impossible to find out which is better between fire needle and moxibustion due to the limited studies. Clinically, appropriate treatment should be selected according to the actual situation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, CRD42021278233.

RBC Folate and Serum Folate, Vitamin B-12, and Homocysteine in Chinese Couples Prepregnancy in the Shanghai Preconception Cohort.

BACKGROUND: The protective effects of maternal folate on neural tube defects are well-established. Emerging evidence has shown paternal folate also is related to pregnancy outcome and offspring health. OBJECTIVES: This study aimed to assess the status of red blood cell (RBC) folate and serum folate, vitamin B-12, and homocysteine (Hcy) and their associated factors in a cohort of pregnancy-preparing couples. METHODS: This was a cross-sectional study involving 14,178 participants from the extension of the Shanghai Preconception Cohort conducted in 2018-2021. Circulating biomarker concentrations were measured, and the prevalence of abnormal status was reported. Linear and logistic regression analyses were conducted to examine associations of demographic factors (age, education, and income), lifestyle factors (smoking, drinking, and folic acid supplement use), and BMI with concentrations of the folate-related biomarkers, abnormal status of folate (deficiency and insufficiency) and vitamin B-12 (deficiency and marginal deficiency), and hyperhomocysteinemia. RESULTS: The geometric mean (95% CI) concentrations of RBC folate, serum folate, vitamin B-12, and Hcy were 490 nmol/L (485, 496 nmol/L), 20.1 nmol/L (19.8, 20.3 nmol/L), 353 pmol/L (350, 357 pmol/L), and 7.54 µmol/L (7.48, 7.60 µmol/L) in females, respectively, and 405 nmol/L (401, 409 nmol/L), 13.5 nmol/L (13.4, 13.7 nmol/L), 277 pmol/L (274, 279 pmol/L), and 12.0 µmol/L (11.9, 12.2 µmol/L) in males, respectively. Prevalence of abnormal status was higher in males than females for the 4 folate-related biomarkers: RBC folate deficiency (<340 nmol/L, 32.2% compared with 18.9%), serum folate deficiency (<10.0 nmol/L, 26.5% compared with 7.3%), RBC folate insufficiency (<906 nmol/L, 96.6% compared with 90.1%), serum folate insufficiency (<15.9 nmol/L, 65.5% compared with 31.4%), vitamin B-12 marginal deficiency (148-221 pmol/L, 21.4% compared with 8.8%), and hyperhomocysteinemia (>15.0 µmol/L, 22.1% compared with 2.5%). CONCLUSIONS: Most pregnancy-preparing couples failed to achieve the optimal RBC folate status (>906 nmol/L) as recommended by the WHO. These findings call for attention to the insufficiency status of folate and promising strategies to improve the folate status of the pregnancy-preparing population not exposed to folic acid fortification.

Maternal liver dysfunction in early pregnancy predisposes to gestational diabetes mellitus independent of preconception overweight: A prospective cohort study.

OBJECTIVE: To evaluate whether the associations of maternal liver dysfunction and liver function biomarkers (LFBs) with gestational diabetes mellitus (GDM) are independent of overweight. DESIGN: Prospective cohort study. METHODS: A sub-cohort of pregnant women with seven LFBs examined at 9-13 weeks of gestation and with complete GDM evaluation at mid-gestation were extracted from the prospective Shanghai Preconception Cohort Study. Associations of liver dysfunction, defined as having any elevated LFB levels, and individual LFB levels with GDM incidence were assessed by adjusting body mass index and other covariates in the multivariable logistic regression model. Odds ratios (ORs) and 95% CI were reported. MAIN OUTCOME MEASURES: Incident GDM. RESULTS: Among 6211 pregnant women, 975 (15.7%) developed GDM. Liver dysfunction was associated with increased odds of GDM (OR 1.63; 95% CI 1.38-1.92). This association persisted after adjustment for BMI (adjusted OR [aOR] 1.37; 95% CI 1.15-1.63). Higher γ-glutamyl transferase, alanine aminotransferase, alkaline phosphatase, and albumin levels were also linked with GDM (aOR per 1 SD: 1.15, 95% CI 1.08-1.23; 1.10, 1.03-1.17; 1.21, 1.13-1.29 and 1.19, 1.11-1.27, respectively). Similar magnitudes of associations were observed between normal weight and overweight pregnant women. CONCLUSION: Maternal liver dysfunction in early pregnancy predisposes women to subsequent GDM, and this association is independent of being overweight preconception. Our findings of an increased risk even in normal-weight pregnant women adds new mechanistic insights about the pathophysiological role of liver function in GDM aetiology. TWEETABLE ABSTRACT: Maternal liver dysfunction in early pregnancy is associated with GDM incidence independent of preconception overweight.

Dynamic trends in skin barrier function from birth to age 6 months and infantile atopic dermatitis: A Chinese prospective cohort study.

BACKGROUND: Skin barrier functions develop after birth and may be related to skin disorders in infants. We aimed to assess associations between dynamic trends of four skin barrier functional parameters in early life with infant atopic dermatitis (AD). METHODS: Based on the prospective cohort MKNFOAD (NCT02889081), we examined transepidermal water loss (TEWL), stratum corneum hydration (SCH), skin pH, and sebum content at five anatomical sites (cheek, forehead, forearm, abdomen, and lower leg) in 418 term infants at birth, 42 days, and 6 months. Trend differences by sex and association with AD at age 1 year were tested using variance analyses. Associations of the parameters with AD risk were tested using discrete time survival analysis, adjusting extensive covariates including parental history of allergy, infant's sex, birth weight (kg), and delivery mode. Odds ratios (ORs) and 95% confidence interval (CIs) were reported. RESULTS: Overall TEWL and SCH appeared trends of increase while skin surface pH and sebum content showed trends of decrease within the first six postnatal months. Sex differences were significant for sebum content only (p < 0.001). After adjustment for parental and children covariates, cheek TEWL at birth (OR = 1.26, 95% CI 1.00-1.57, p = 0.045) and 42 days (OR = 1.52, 95% CI 1.17-1.97, p = 0.002) were significantly associated with increased AD risk. Associations were not observed between SCH, skin pH, and sebum content at birth or 42 days with AD. CONCLUSIONS: Skin barrier functions of Chinese term infants varied nonlinearly after birth. Higher postnatal TEWL levels in early life indicate higher risk of early-onset AD.

Estimated Survival and Major Comorbidities of Very Preterm Infants Discharged Against Medical Advice vs Treated With Intensive Care in China.

Importance: A significant proportion of very preterm infants (<32 weeks' gestation) are discharged against medical advice (DAMA) from neonatal intensive care units in China. There is minimal information available on the potential outcomes of providing complete care before discharge in these infants. Objective: To describe potential neonatal outcomes of DAMA in very preterm infants if they receive complete care based on estimates derived from a group of propensity score-matched infants who are not DAMA. Design, Setting, and Participants: This cohort study enrolled all infants born at between 24 and 31 weeks' gestation from May 1, 2015, to April 30, 2018, and admitted to 25 tertiary neonatal intensive care units across China within 7 days of birth. A multilevel mixed-effects logistic regression model was constructed to estimate the propensity score for the likelihood of DAMA for each infant. Infants who were not DAMA were then matched to DAMA infants with the closest propensity score on a 1:1 ratio by using a nearest neighbor greedy matching algorithm without replacement. Incidences of neonatal outcomes were then calculated among the matched non-DAMA infants to simulate the outcomes of DAMA infants. Statistical analyses were performed from August 16, 2020, to September 26, 2020. Exposures: Discharge against medical advice, which was defined as termination of treatment and discharge before the treating physicians recommended discharge. Main Outcomes and Measures: Survival and survival without major morbidity. Results: The study enrolled a total of 14 083 infants (8141 boys [57.8%]) with a median gestational age of 30.1 weeks (interquartile range [IQR], 29.0-31.1 weeks) and a median birth weight of 1400 g (IQR, 1170-1600 g). Overall, 1876 of 14 083 very preterm infants (13.3%; 95% CI, 12.8%-13.9%) were DAMA, of whom 1367 of 1876 (72.9%; 95% CI, 70.8%-74.8%) required intensive care on discharge. A total of 1473 DAMA infants were successfully matched to 1473 non-DAMA infants. Overall, 1211 of 1473 matched non-DAMA infants (82.2%; 95% CI, 80.2%-84.1%) survived to discharge. The survival rates were 68.3% (95% CI, 62.4%-73.7%) for infants at 26 to 27 weeks' gestation, 84.1% (95% CI, 80.7%-87.0%) for infants 28 to 29 weeks' gestation, and 92.4% (95% CI, 90.0%-94.2%) for infants at 30 to 31 weeks' gestation. A total of 872 of 1473 matched non-DAMA infants (59.2%; 95% CI, 56.7%-61.7%) survived without any major morbidity. Conclusions and Relevance: The results of this cohort study suggest that very preterm infants who are DAMA from neonatal intensive care units may have intact survival if complete care is provided. Efforts to reduce DAMA may be associated with improved outcomes of very preterm infants in China.