Sex-specific longitudinal association between baseline physical activity level and cognitive decline in Chinese over 45 years old: Evidence from the China health and retirement longitudinal study.

OBJECTIVES: To examine whether sex-specific associations between baseline PA level and follow up cognitive performance in Chinese subjects exist from the China Health and Retirement Longitudinal study (CHARLS). METHOD: A total of 3395 adults aged 45 or old from the CHARLS were used for analysis. The combined scores of measurements of mental status and verbal episodic memory were utilized for assessing cognitive function at baseline in 2011 and the follow-up survey in 2015. Baseline PA level was quantified as the total PA score. Multiple linear regression and logistic regression models were used to examine the association between baseline PA status and global cognitive function and cognitive domains. RESULTS: In the female subjects (n = 1748), compared with individuals of PA level in the lower tertile, those grouped into the upper tertile had the lowest risk of global cognitive decline [odds ratio (OR) =0.273, 95% confidence interval (CI) =0.077-0.960; p = 0.043] and verbal episodic memory decline [OR)=0.257, 95% CI =0.066-1.003; p = 0.051] from 2011 to 2015. However, no significant associations were observed in the male subjects (n = 1647). CONCLUSION: In the female subjects, higher PA level was associated with reduced risk of cognitive decline within 4 years, this might be associated with reduced decline of verbal episodic memory. Our findings confirmed that female sex would positively affect the association between PA levels and cognitive decline.

School-based surveillance on visit-to-visit blood pressure variability and high blood pressure in children and adolescents.

BACKGROUND: The predictive importance of visit-to-visit blood pressure variability (VVV) for high blood pressure (HBP) in a pediatric population has been largely unsettled. We aimed to evaluate it based on Health Promotion Program for Children and Adolescents (HPPCA), a school-based surveillance conducted from 2012 to 2018 in Suzhou, China. METHODS: A total of 330,618 participants had BP measurement in 2018 and ≥ 3 BP records during 2012-2017, were recruited from HPPCA. Absolute BP values (in mmHg) were converted into age-, sex- and height- normalized z-scores. VVV was expressed as standard deviation (SD), coefficient of variation (CV) or average real variability (ARV) of BP z-scores during 2012-2017. Logistic regression models were used to assess the associations between VVV and HBP in 2018. RESULTS: In 2018, 42,554 (12.87%) subjects were defined as HBP. VVV, except for SBP-CV and DBP-CV, was significantly higher in the HBP group than normotensives group. After adjusting for covariates including mean BP values from 2012 to 2017, SBP-SD, SBP-ARV, DBP-SD and DBP-ARV, increased the risk of HBP by 5.70 [95% confidence interval (95% CI) 5.54-5.87], 4.10 (95% CI 4.01-4.20), 4.70 (95% CI 4.50-4.90) and 3.39 (95% CI 3.28-3.50) times, respectively. Notably, SBP-SD significantly improved risk discrimination of HBP based on other risk variables (c-statistics, net reclassification index and integrated discrimination improvement significantly increased). CONCLUSIONS: Higher SD or ARV of BP, was independently related with higher probability of HBP in Chinese pediatric population. SBP-SD could be potentially helpful for detecting HBP. Future researches investigating the predictive value of VVV are warrant.

Gestational systolic blood pressure trajectories and risk of adverse maternal and perinatal outcomes in Chinese women.

BACKGROUND: Associations between trajectories of systolic blood pressure (SBP) during pregnancy and pregnant outcomes remain unclear and disparate. METHODS: Data of 20,353 mothers without chronic hypertension and who delivered live singletons between January, 2014 and November, 2019, was extracted from Taicang register-based cohort. Based on SBP measured during 10 to 40 weeks of gestation, SBP trajectories were explored using latent class growth mixture model, and their associations with maternal and neonatal outcomes were assessed by logistic regression analyses. RESULTS: Six heterogeneous SBP trajectories were identified: low delayed-increasing (7.47%), low reverse-increasing (21.88%), low-stable (19.13%), medium-stable (21.64%), medium reverse-increasing (16.47%), and high stable (13.41%) trajectories. The high-stable trajectory had SBP around 125 mmHg in the 10th gestational week, and increased slightly onwards. When compared with the low-stable trajectory, the high-stable trajectory had maximally adjusted odds ratio (95% confidence interval) of 5.28 (2.76-10.10), 1.30 (1.13-1.50), 1.53 (1.12-2.08), 1.32 (1.06-1.65) and 1.64 (1.08-2.48) for gestational hypertension (GH), early-term delivery (ETD), preterm delivery (PTD), small for gestational age and low birth weight (LBW), respectively. Besides, the medium reverse-increasing trajectory showed significantly increased risk of GH and ETD, while the medium-stable trajectory had significantly elevated risk of ETD and PTD. Notably, SBP trajectories slightly but significantly improved risk discrimination of GH, ETD and LBW, over traditional risk factors. CONCLUSION: Women with different SBP trajectories were at varied risk of adverse maternal and fetal outcomes. Meanwhile, our study suggested that BP monitoring during pregnancy is necessary, especially for women with high SBP in early pregnancy or upward trajectory.

Association between maternal vitamin D status with pregnancy outcomes and offspring growth in a population of Wuxi, China.

BACKGROUND AND OBJECTIVES: The role of maternal vitamin D in infantile growth remains unclear. METHODS AND STUDY DESIGN: Serum 25-hydroxyvitamin D [25(OH)D] concentrations were examined for pregnancies who visited the Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University from January 2016 to December 2017. Anthropometric measurements of corresponding offspring were performed from birth to 2 to 3 years old. Infantile body mass index (BMI) was transformed into age-, sex- and height- normalized z scores, and Latent Class Growth Mixture (LCGM) model was used to identify trajectories of BMI-Z. RESULTS: Among the 329 included pregnancy women, 109 (33.13 %), 190 (57.75%) and 30 (9.12%) were defined as vitamin D deficiency [25(OH)D <30 nmol/L], insufficiency [30 nmol/L≤25(OH)D<50 nmol/L] and sufficiency [25(OH)D ≥50 nmol/L], respectively. When compared with vitamin D sufficiency, maternal vitamin D deficiency was not associated with preterm birth [odds ratio (OR)=2.69, 95% confidence interval (95% CI)=0.57-12.80], small for gestation age (OR=0.99, 95% CI=0.29-3.46), and low birth weight (OR=1.69, 95% CI=0.34-8.51). Similarly, no significant relationships were found between maternal vitamin D concentrations and anthropometric indices (such as weight, length, BMI) during 0 to 3 years old. Furthermore, LCGM model identified two patterns of offspring growth: stable moderate BMI-Z and early transient BMI-Z groups. Maternal vitamin D levels were higher in the former group than the latter (p=0.037); however, maternal vitamin D status appeared to be unrelated with offspring BMI-Z trajectories in multivariable logistic regression models. CONCLUSIONS: Maternal vitamin D deficiency may not be related to adverse pregnancy outcomes as well as offspring growth.

Relationship Between Plasma Growth Differentiation Factor 15 Levels and Complications of Type 2 Diabetes Mellitus: A Cross-sectional Study.

OBJECTIVE: Our aim in this study was to identify the associations between growth differentiation factor 15 (GDF15) and type 2 diabetes mellitus (T2DM) complications in a community-based population in China. METHODS: Based on a cross-sectional study registered in the National Basic Public Health Service for disease management of Changshu in China, a total of 1,689 T2DM patients were enrolled and tested further for plasma GDF15 levels. Macrovascular (cardiovascular disease and diabetic foot) and microvascular (diabetic kidney disease [DKD], diabetic retinopathy, and neuropathy) complications were evaluated. Logistic regression models were conducted to identify the associations of GDF15 with the risk of diabetes complications, and linear regression models were used to assess relationships between GDF15 and other clinical features. RESULTS: Overall, 459 of the 1,689 T2DM patients (27.18%) had complications. GDF15 levels were significantly higher in patients with any type of complication compared with their counterparts. With each standard deviation increase of base 10 logarithms of GDF15 (lg-GDF15), the risk of overall complications increased by 1.17-fold (95% confidence interval [CI], 1.03 to 1.32). In contrast to macrovascular complications, associations of GDF15 with microvascular complications appeared to be stronger (adjusted odds ratio [OR], 1.24; 95% CI, 1.08 to 1.43), especially for DKD (adjusted OR, 1.51; 95% CI, 1.19 to 1.93). Subgroup analyses showed that the strength of association between GDF15 and complications varied by distinct age and T2DM duration subgroups. Patients with 2 or more types of complications had higher levels of GDF15 than those with fewer types of complications. Also, linear relationships were identified between GDF15 and several liver and kidney function indices. CONCLUSION: Higher GDF15 levels were associated with T2DM complications, especially DKD. GDF15 may serve as a biomarker for monitoring the deterioration of T2DM.

Corrigendum: Impact of SARS-CoV-2 Infection During Pregnancy on Infant Neurobehavioral Development: A Case-Control Study.

[This corrects the article DOI: 10.3389/fped.2021.762684.].

Identification of Biomarkers for Preeclampsia Based on Metabolomics.

Background: Preeclampsia (PE) is a significant cause of maternal and neonatal morbidity and mortality worldwide. However, the pathogenesis of PE is unclear and reliable early diagnostic methods are still lacking. The purpose of this review is to summarize potential metabolic biomarkers and pathways of PE, which might facilitate risk prediction and clinical diagnosis, and obtain a better understanding of specific metabolic mechanisms of PE. Methods: This review included human metabolomics studies related to PE in the PubMed, Google Scholar, and Web of Science databases from January 2000 to November 2021. The reported metabolic biomarkers were systematically examined and compared. Pathway analysis was conducted through the online software MetaboAnalyst 5.0. Results: Forty-one human studies were included in this systematic review. Several metabolites, such as creatinine, glycine, L-isoleucine, and glucose and biomarkers with consistent trends (decanoylcarnitine, 3-hydroxyisovaleric acid, and octenoylcarnitine), were frequently reported. In addition, eight amino acid metabolism-related, three carbohydrate metabolism-related, one translation-related and one lipid metabolism-related pathways were identified. These biomarkers and pathways, closely related to renal dysfunction, insulin resistance, lipid metabolism disorder, activated inflammation, and impaired nitric oxide production, were very likely to contribute to the progression of PE. Conclusion: This study summarized several metabolites and metabolic pathways, which may be associated with PE. These high-frequency differential metabolites are promising to be biomarkers of PE for early diagnosis, and the prominent metabolic pathway may provide new insights for the understanding of the pathogenesis of PE.

Blood pressure categories defined by the 2017 ACC/AHA guideline and all-cause mortality: a national cohort study in China and meta-analysis.

The 2017 American College of Cardiology/American Heart Association guideline recommends a lowered threshold for hypertension diagnosis. Nonetheless, the association of blood pressure (BP) groups defined by the new guideline and all-cause mortality has not been fully estimated, especially in general Chinese. Based on the China Health and Retirement Longitudinal Study (CHARLS) during 2011-2018, 12,964 participants aged 45 years or older at baseline were enrolled for a follow-up of 7 years. Cox proportional hazards models were used to examine the relationship of BP classifications with all-cause mortality, with normal BP (<120/80 mmHg) as a reference. Afterwards, eligible studies shed light in this field were searched in public databases, and meta-analysis was conducted. In CHARLS, there were 41.21% and 16.08% individuals with stage 2 hypertension and stage 1 hypertension, respectively. During the follow-up, 1293 death occurred. The redefined stage 1 (130-139/80-89 mmHg) and stage 2 hypertension (≥140/≥90 mmHg) were found to have increased risk of death in the crude model, but only stage 2 hypertension maintained statistically significance after adjustment. Furthermore, meta-analysis including CHARLS and nine other prospective studies, with a total of 290,609 participants followed up for 3,081,532 person-years, resulted in similar results (combined hazard ratio (95% confidence interval) was 1.07 (0.99-1.15) for stage 1 hypertension, and 1.39 (1.25-1.53) for stage 2 hypertension). The present study detected that individuals with stage 2 and stage 1 hypertension had increased likelihood to die from any cause, but only the former association achieved statistically significance. Further cohorts with long-term follow-up duration are warranted, especially in China.

Stage 1 hypertension defined by the 2017 ACC/AHA guidelines and neonatal outcomes: Systematic review and meta-analysis.

BACKGROUND: In 2017, the American College of Cardiology/ American Heart Association (ACC/AHA) guidelines redefined the threshold of high blood pressure (BP) for non-pregnant adults. Several studies aimed to determine whether lowering these thresholds should be considered for pregnancies to prevent poor neonatal outcomes, but the results were inconclusive. METHODS: We perform a systematic review and meta-analysis to evaluate the association between BP groups defined by the 2017 ACC/AHA guidelines and pregnancy outcomes. Relevant literature was searched in PubMed, Google Scholar, Embase, and Web of Science up to 18 May 2021. RESULTS: Sixteen eligible studies from twelve articles with a total of 303,131 pregnancies were identified, encompassing 233,084, 20,859, 39,379 individuals with normal BP, elevated BP, and stage 1 hypertension, respectively. When compared with normal BP, the combined odds ratio (95% confidence interval) of elevated BP for adverse pregnancy outcomes was not significant; whereas, that of stage 1 hypertension were 1.25 (1.13-1.39), 1.16 (1.03-1.31), 1.50 (1.28-1.77) and 1.12 (1.00-1.25) for preterm delivery, small for gestational age, low birth weight, and early-term delivery, respectively. CONCLUSION: Our results indicated that stage 1 hypertension increased the risk of poor neonatal outcomes, highlighting the importance of recognition of stage 1 hypertension as a risk indicator for poor pregnancy outcomes.

Impact of SARS-CoV-2 Infection During Pregnancy on Infant Neurobehavioral Development: A Case-Control Study.

Background: Previous studies on the pneumonia outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on the general population and pregnant women, while little is known about the effects of SARS-CoV-2 on retardation during and after pregnancy. The purpose of this study was to evaluate the potential influence of SARS-CoV-2 on infant neurobehavioral development. Methods: A case-control study was conducted in Wuhan Maternal and Child Health Hospital, China. Nine pregnant women with SARS-CoV-2 infection and 9 controls matched by maternal age, parity, and status of chronic disease were included. Infantile neurobehavioral development was assessed through the Ages and Stages Questionnaires Edition 3 (ASQ-3). Results: The majority of pregnant women with SARS-CoV-2 experienced cesarean section (7 of 9), which was higher than the control group (5 of 9). The throat swabs of all newborn were negative. We found that compared with the control group, neonates of mothers with SARS-CoV-2 infection during pregnancy had lower scores in communication, gross movement, fine movement, problem solving, and personal-social domains; but only fine movement domain yielded statistical significance (P = 0.031). Conclusion: Infection with SARS-CoV-2 during pregnancy may have a certain impact on infant neurobehavioral development. Further studies with larger sample size are warranted for validation.

BMI Trajectories During the First 2 Years, and Their Associations With Infant Overweight/Obesity: A Registered Based Cohort Study in Taizhou, China.

Objective: The purpose of this study was to identify trajectories of body mass index (BMI) in toddlers from birth to 2 years old and examine their association with infantile overweight/obesity. Methods: Data were collected from 19,054 children born in any hospital or community healthcare center in Taizhou, China from 2018 to 2019 with at least three BMI measurements after birth. The Latent Class Growth Mixture Model was used to identify distinct BMI trajectories during the first 2 years of infants. Multiple logistic regression models were conducted to explore the associated factors of different BMI trajectories, and log-binomial regression was performed to assess the association between the trajectories and overweight/obesity. Results: Three heterogeneous BMI trajectories were identified and labeled as "lower" (36.21%, n = 6,899), "middle" (53.15%, n = 10,128) and "upper" (10.64%, n = 2,027), respectively. Several characteristics of infants and their corresponding mothers were found to be correlated with infant BMI trajectories, including infant sex, mode of delivery and weight at birth, as well as maternal parity, early pregnancy BMI and status of gestational diabetes mellitus. Furthermore, compared with those in the lower trajectory, infants in the middle [prevalence ratio (PR) = 2.63, 95% confidence interval (95%CI) = 2.17-2.63] or upper (PR = 2.98, 95%CI = 1.51-2.98) trajectory groups were prone to be overweight/obesity at their final observation. Conclusion: Heterogeneous BMI trajectories were observed in our study. Characteristics of both infants and their corresponding mothers could be potential determinants of infant growth. Moreover, infants in the middle and upper trajectory groups were more likely to suffer overweight/obesity.

Body Mass Index Trajectories during 6-18 Years Old and the Risk of Hypertension in Young Adult: A Longitudinal Study in Chinese Population.

BACKGROUND: Overweight/obesity in childhood is suggested to increase the risk of hypertension later in life. We aimed to assess whether and how body mass index (BMI) trajectories during 6-18 years of age are associated with hypertension in young adulthood (18-37 years) in the Chinese population. METHODS: Based on the China Health and Nutrition Survey (CHNS), a total of 1,872 participants who received ≥2 measurements of BMI during 6-18 years and had assessment of blood pressure (BP) in young adulthood were included. BMI trajectories were explored using latent class growth mixture models, and associations between identified trajectories with hypertension in young adulthood were examined by logistic regression analyses. RESULTS: Five heterogeneous BMI trajectories were identified: the low slow-increasing (20.03%), low moderate-increasing (56.14%), low rapid-increasing (17.04%), moderate-increasing (3.63%), and elevated-decreasing (3.15%) groups. Compared with the low slow-increasing group, another three increasing groups had gradually elevated risk of hypertension, yielding maximally adjusted odds ratio (95% confidence interval) (OR (95% CI)) of 2.48 (1.39-4.42), 3.24 (1.66-6.31), and 3.28 (1.19-9.08), respectively, whereas the elevated-decreasing group reversed overweight/obesity to normal weight in childhood, rendering its association with hypertension as not statistically significant (OR (95% CI) = 2.74 (0.98-7.65)). CONCLUSION: Our study indicates that there are varied BMI trajectories from childhood to adulthood and that an elevated BMI trajectory during childhood is related with an increased risk of hypertension in young adulthood. In contrast, weight loss of children with high initial BMI may mitigate or reverse the risk. Our findings emphasize the importance of BMI continuous monitoring during early life.

Visit-to-visit blood pressure variability and risk of adverse birth outcomes in pregnancies in East China.

To investigate the potential associations between visit-to-visit blood pressure variability (VVV) and adverse birth outcomes in pregnancies, 48,209 pregnant women without proteinuria or chronic hypertension before 20 weeks of gestation who delivered live singletons between January 2014 and November 2019 in Taizhou or Taicang cities were recruited. VVV was estimated as the standard deviation and coefficient of variation of blood pressure [i.e., systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP)] measured from 20 weeks of gestation onwards. Pregnant women were classified into four groups according to the corresponding quartiles for each VVV index. It was found that VVV was significantly higher in women with small for gestational age (SGA) or low birth weight (LBW) infants than in their counterparts. Graded associations between VVV categories and poor birth outcomes were observed. In particular, when comparing the women with the highest to the lowest quartiles of standard deviation and coefficient variation of DBP, the odds ratios (95% confidence interval) for SGA was 1.15 (1.06-1.26) and 1.14 (1.05-1.25), respectively. Interestingly, the addition of DBP-VVV to established risk factors improved risk prediction of SGA; DBP-VVV demonstrated modestly superior predictive performance to VVV obtained from SBP or MAP. Similar results were found even among normotensive pregnancies. Our findings indicated that VVV during pregnancy, especially DBP-VVV, was independently associated with poor birth outcomes of pregnancies in East China. The inclusion of DBP-VVV with established risk factors may help in identifying pregnancies at high risk of SGA. Validations are needed.

Association between serum 25-hydroxyvitamin D concentrations and obesity in one-year-old Chinese infants.

Recent studies suggested that vitamin D is linked with obesity, but evidence in infants is scarce. Therefore, we aimed to make an exploration in infants. A total of 414 infants at one year old who visited Maternity and Child Health Care Hospital of Wuxi in China were recruited. Finger-stick blood sampling was conducted in all the subjects, and serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured. Maternal characteristics during pregnancy and infantile information were collected by questionnaires or extracting from medical records. Multivariable linear models were performed to assess the relationship between 25(OH)D and body mass index (BMI), while multivariable logistic regression models were used to examine the association between 25(OH)D and obesity. Among the 414 infants, 69 (16.67%) and 81 (19.57%) infants were defined as obesity and vitamin D deficiency [25(OH)D < 50 nmol/L], respectively. The mean (SD) of 25(OH)D concentration was 68.05 (19.05) in infants without obesity, which was significantly higher than that of obese infants [60.36(18.49), p = .002]. Inverse linear relationships were observed between 25(OH)D level and BMI (ß = -0.017, p = .004) as well as BMI Z-score (ß = -0.010, p = .004). Furthermore, vitamin D deficiency was associated with an increased risk of obesity of infants (adjusted odds ratio = 2.74, 95% confidence interval = 1.20-6.25, with 25(OH)D ≥ 75 nmol/L as a reference). The results showed that serum 25(OH)D concentrations were significantly lower in infants with obesity, suggesting vitamin D deficiency may be an independent risk factor for obesity among one-year-old Chinese infants.

Stage 1 hypertension defined by the 2017 American College of Cardiology/American Heart Association guideline and risk of adverse birth outcomes in Eastern China.

OBJECTIVE: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline recommended a lower threshold (130/80 mmHg) for hypertension in nonpregnant adults. However, the influence of this guideline in Chinese pregnant women is not well characterized. METHODS: Data of 32 742 and 14 479 mothers who had blood pressure (BP) less than 130/80 mmHg and no proteinuria before 20 gestational weeks and delivered live singletons between 1 January 2014 and 30 November 2019 were extracted from Taizhou and Taicang register-based cohorts, respectively. The average measured BP in the third trimester was obtained and categorized according to the 2017 ACC/AHA guideline. The association between BP and risk of adverse birth outcomes was assessed by multivariate logistic regression analysis. RESULTS: In the third trimester, 331 (1.01%) and 378 (2.61%) women had mean BP at least 140/90 mmHg, but 2435 (7.44%) and 1054 (7.28%) had stage 1 hypertension (130-139/80-89 mmHg) in Taizhou and Taicang, respectively. Significant associations between stage 1 hypertension and small for gestational age [odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.14-1.52] and low birth weight (OR = 1.81, 95% CI = 1.46-2.25) were observed in the Taizhou population. Consistent results were also shown in the Taicang population [OR (95% CI), of 1.46 (1.18-1.79) and 1.50 (1.07-2.11), respectively]. CONCLUSION: Stage 1 hypertension in the third trimester defined by the 2017 ACC/AHA guideline was associated with an increased risk for adverse birth outcomes in Eastern Chinese pregnant women, suggesting that this guideline may improve the detection of high BP and surveillance of adverse neonatal outcomes in China.

Association between MIC-1 and Type 2 Diabetes: A Combined Analysis.

BACKGROUND AND OBJECTIVES: Type 2 diabetes mellitus (T2DM) is an epidemic disease that endangers human health seriously. Recently, a large number of reports have revealed that macrophage-inhibiting cytokine-1 (MIC-1) is linked with T2DM, but the results were inconclusive. The aim of this study was to perform bioinformatics analysis of the association between MIC-1 and T2DM. MATERIAL AND METHODS: Datasets and relevant literatures were searched in Gene Expression Omnibus (GEO), PubMed, Google Scholar, and Web of Science till September 20, 2019. Expression levels of MIC-1 were extracted, pooled, and compared between T2DM cases and controls. RESULTS: In summary, 11 GEO datasets and 3 articles with 421 T2DM cases and 711 controls were finally included. The expression level of MIC-1 was significantly higher in T2DM patients compared with controls, with a standard mean difference (SMD) of 0.54 and a 95% confidence interval (95% CI) of 0.24-0.83; in blood samples, the difference was still significant (SMD = 0.65; 95%CI = 0.24-1.06). Meanwhile, the expression level of MIC-1 plays a significant role in differentiating T2DM cases from controls; the combined sensitivity, specificity, and odds ratio were 0.83 (95%CI = 0.72-0.90), 0.59 (95%CI = 0.45-0.72), and 1.64 (95%CI = 1.35-1.99), respectively. The summary receiver operating characteristic (SROC) curve demonstrated that the area under the curve (AUC) was 0.81 (95%CI = 0.77-0.84). CONCLUSION: Our results suggested that the expression levels of MIC-1 were significantly higher in T2DM patients in multiple tissues including blood samples.