COVID-19 Pandemic and Stroke Care in Patients with Dementia Compared to Other Stroke Patients.

OBJECTIVES: The primary objective of this study was to examine the impact of the COVID-19 pandemic on the quality of stroke care for patients with preexisting dementia, compared with patients who had only stroke. The secondary aim was to investigate how the quality of stroke care changed during the pandemic and post-pandemic periods compared with the pre-pandemic period in patients with preexisting dementia. DESIGN: A registry-based, nationwide cohort study in Sweden. SETTING AND PARTICIPANTS: We included patients with a first stroke between 2019 and 2022, both with and without dementia. The study periods were defined as follows: pre-pandemic (January 1, 2019, to February 29, 2020), COVID-19 pandemic (March 1, 2020, to February 24, 2022), and post-COVID-19 pandemic period (February 25, 2022, to September 19, 2022). The outcomes examined were the following quality indicators of stroke care, suggested by the national guideline of stroke care in Sweden: stroke admission site, performance of swallowing assessment, reperfusion treatment, assessment for rehabilitation, and early supported discharge. METHODS: The associations were studied through group comparisons and binary logistic regressions. RESULTS: Of the 21,795 patients with strokes, 1357 had documented preexisting dementia, and 20,438 had stroke without a dementia diagnosis. Throughout all study periods, a significantly lower proportion of patients with stroke with preexisting dementia, compared with stroke-only patients, received reperfusion treatment, assessments for rehabilitation, and early supported discharge from stroke units. In the subgroup of stroke patients with preexisting dementia, no significant associations were found regarding the quality indicators of stroke care before, during, and after the pandemic. CONCLUSIONS AND IMPLICATIONS: Disparities in quality of stroke care were observed between stroke patients with preexisting dementia and those with only stroke during the COVID-19 pandemic. However, there were no statistically significant differences in stroke care for patients with dementia across the pandemic.

The Association between Birthweight and Use of Cardiovascular Medications: The Role of Health Behaviors.

BACKGROUND: There is limited evidence on the effect of low birthweight on the use of cardiovascular medications and the role of health behaviors. This study aims to determine the independent effect of low birthweight and its combination with adult health behaviors on the number of dispensed cardiovascular medications. METHODS: We included 15618 participants with information on birthweight and self-reported health behaviors. Dispensed cardiovascular medications were identified from the Prescribed Drug Register based on a three-digit level Anatomical Therapeutic Chemical classification code (C01 to C10 and B01) and categorized into 0, 1, and ≥2 different types of medications. We applied multinomial logistic regression models estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Participants with low birthweight had a higher estimated OR of using ≥2 types of cardiovascular medications (OR = 1.46, 95% CI = 1.06, 2.01). Further, an increased risk for using ≥2 types of cardiovascular medications was found in participants with poor health behaviors for normal (OR = 2.17, 95% CI = 1.80, 2.62) and high (OR = 1.84, 95% CI = 1.29, 2.62) birthweight. The strongest effect on using ≥2 types of cardiovascular medications was found for low birthweight and poor health behaviors (OR = 3.14, 95% CI = 1.80, 5.50). CONCLUSION: This cohort study provides evidence that low birthweight increases the risk of using more types of cardiovascular medications in adulthood. This study also suggests that ideal health behaviors reduce this risk.

Psychiatric Disorders Before and After Dementia Diagnosis.

Importance: Little is known about the specific timing and sequence of incident psychiatric comorbidities at different stages of dementia diagnosis. Objectives: To examine the temporal risk patterns of psychiatric disorders, including depression, anxiety, stress-related disorders, substance use disorders, sleep disorders, somatoform/conversion disorders, and psychotic disorders, among patients with dementia before, at the time of, and after receipt of a diagnosis. Design, Setting, and Participants: This population-based, nationwide cohort study analyzed data from 796 505 participants obtained from 6 registers between January 1, 2000, and December 31, 2017, including the Swedish registry for cognitive/dementia disorders. Patients with dementia were matched on year of birth (±3 years), sex, and region of residence with up to 4 controls. Data were analyzed between March 1, 2023, and August 31, 2023. Exposures: Any cause of dementia and dementia subtypes. Main Outcomes and Measures: Flexible parametric survival models to determine the time-dependent risk of initial diagnosis of psychiatric disorders, from 7 years prior to dementia diagnosis to 10 years after diagnosis. Subgroup analysis was conducted for psychiatric drug use among persons receiving a diagnosis of dementia from January 1, 2011, to December 31, 2012. Results: Of 796 505 patients included in the study (mean [SD] age at diagnosis, 80.2 [8.3] years; 448 869 (56.4%) female), 209 245 had dementia, whereas 587 260 did not, across 7 824 616 person-years. The relative risk of psychiatric disorders was consistently higher among patients with dementia compared with control participants and began to increase from 3 years before diagnosis (hazard ratio, [HR], 1.72; 95% CI, 1.67-1.76), peaked during the week after diagnosis (HR, 4.74; 95% CI, 4.21-5.34), and decreased rapidly thereafter. Decreased risk relative to controls was observed from 5 years after diagnosis (HR, 0.93; 95% CI, 0.87-0.98). The results were similar for Alzheimer disease, mixed dementia, vascular dementia and unspecified dementia. Among patients with dementia, markedly elevated use of psychiatric medications was observed in the year leading up to the dementia diagnosis and peaked 6 months after diagnosis. For example, antidepressant use was persistently higher among patients with dementia compared with controls, and the difference increased from 2 years before dementia diagnosis (15.9% vs 7.9%, P < .001), peaked approximately 6 months after dementia diagnosis (29.1% vs 9.7%, P < .001), and then decreased slowly from 3 years after diagnosis but remained higher than controls 5 years after diagnosis (16.4% vs 6.9%, P < .001). Conclusions and Relevance: The findings of this cohort study that patients with dementia had markedly increased risks of psychiatric disorders both before and after dementia diagnosis highlight the significance of incorporating psychiatric preventative and management interventions for individuals with dementia across various diagnostic stages.

The Association of Reproductive Hormones During the Menstrual Period with Primary Dysmenorrhea.

Objective: This study aimed to investigate the association of reproductive hormones with primary dysmenorrhea in Chinese women. Methods: A case-control study was conducted and patients with primary dysmenorrhea and non-dysmenorrhea participants were recruited. Oxytocin, PGF2α, vasopressin, estriol and estradiol were respectively measured in plasma collected three to five days after menstruation. Restricted cubic spline and multiple logistic regression models were adopted to analyze the association between hormones and primary dysmenorrhea. Results: There were 604 participants enrolled in our study including 300 patients with primary dysmenorrhea. After adjustment for the potential confounders, oxytocin levels (Q3: OR (95% CI) = 0.50 (0.27~0.95) (p=0.035); Q4: 0.34 (0.17~0.66) (p=0.001)) and PGF2α levels (Q3: 0.45 (0.24~0.87) (p=0.017); Q4: 0.43 (0.22~0.84) (p=0.013)) were respectively associated with an decreased risk of primary dysmenorrhea, but estradiol (Q2: 2.18 (1.13~4.19) (p=0.020); Q3: 2.17 (1.12~4.19) (p=0.022)) and vasopressin (Q3: 2.88 (1.48~5.63) (p=0.002); Q4: 3.20 (1.65~6.22) (p<0.001)) with an increased risk of primary dysmenorrhea, respectively. Among patients with primary dysmenorrhea, the higher estriol level was associated with higher frequent dysmenorrhea (Q2: 3.12 (1.32~7.34) (p=0.009); Q3: 4.97 (2.08~11.85) (p<0.001)) and always dysmenorrhea (Q2: 2.51 (1.03~6.11) (p=0.041); Q3: 3.10 (1.25~7.73) (p=0.015)). Similarly, high estriol levels were associated with the higher degree of pain significantly only when hormone levels were at a high level (Q3: 2.06 (1.03~4.18) (p=0.043)). Conclusion: Higher serum vasopressin and estradiol concentrations as well as lower oxytocin and PGF2α levels were associated with higher risk of primary dysmenorrhea. Estrogen showed a reverse U-shape association on the frequency and degree of pain among patients with primary dysmenorrhea.

Efficacy of intermittent versus daily vitamin D supplementation on improving circulating 25(OH)D concentration: a Bayesian network meta-analysis of randomized controlled trials.

Background: Vitamin D deficiency is a widespread issue globally, resulting in increased use of vitamin D supplements. However, it is unclear whether intermittent (weekly or monthly) vitamin D supplementation is as effective as daily supplementation in improving circulating 25-hydroxyvitamin D [25(OH)D] levels. Methods: Three databases including Medline, EMBASE, and the Cochrane Library were systematically searched up to 10 November 2020. The risk of bias was evaluated according to Cochrane Collaboration's tool for rating methodological quality assessment. Direct and indirect comparisons between interventions and controls were performed by a Bayesian network meta-analysis (NMA), where the mean difference (MD) and its 95% confidence interval (CI) were used to indicate the efficacy. Results: This NMA analysis included 116 RCTs with a total of 11,376 participants. Generally, we observed that 25(OH)D concentrations were significantly elevated regardless of vitamin D supplementation frequency. Although the findings of SUCRA indicated that daily vitamin D supplementation had a higher rank value than intermittent supplementation when the supplement dosage was similar, no statistically significant pooled mean differences of 25(OH)D concentration were noted between the daily supplementation group and intermittent supplementation group. Additionally, weekly supplementation with a total of 600,000 IU vitamin D supplementation during 3 months had the best efficacy in elevating 25(OH)D concentration (pooled MD = 63 nmol/L, 95%CI: 49-77). To achieve optimal 25(OH)D concentration (>75 nmol/L), we recommend 60,000 IU vitamin D supplementation monthly (~2,000 IU/day). Conclusion: The efficacy of intermittent vitamin D supplementation was similar to daily supplementation. Coupled with its convenience, the frequency and dosage of intermittent vitamin D supplements were recommended to reach the optimal 25(OH)D level.Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=257257, PROSPERO CRD42021257257.

External Causes of Death From Death Certificates in Patients With Dementia.

OBJECTIVES: We aim to analyze the risk of death from specific external causes, including falls, complications of medical and surgical care, unintentional injuries, and suicide, in dementia patients. DESIGN: Swedish nationwide cohort study integrating 6 registers from May 1, 2007, through December 31, 2018, including the Swedish Registry for Cognitive/Dementia Disorders (SveDem). SETTING AND PARTICIPANTS: Population-based study. Patients diagnosed with dementia from 2007 to 2018 and up to 4 controls matched on year of birth (±3 years), sex, and region of residence. METHODS: The exposures of this study were diagnosis of dementia and dementia subtypes. Number of deaths and causes of mortality were obtained from death certificates compiled into the Cause of Death Register. Hazard ratios (HRs) and 95% CIs were estimated using Cox and flexible models, adjusted for sociodemographics, medical and psychiatric disorders. RESULTS: The study population included 235,085 patients with dementia [96,760 men (41.2%); mean age 81.5 (SD 8.5) years] and 771,019 control participants [341,994 men (44.4%); mean age 79.9 (SD 8.6) years], over 3,721,687 person-years. Compared with control participants, patients with dementia presented increased risk for unintentional injuries (HR 3.30, 95% CI 3.19-3.40) and falls (HR 2.67, 95% CI 2.54-2.80) during old age (≥75 y), and suicide (HR 1.56, 95% CI 1.02-2.39) in middle age (<65 y). Suicide risk was 5.04 times higher (HR 6.04, 95% CI 4.22-8.66) in patients with both dementia and 2 or more psychiatric disorders relative to controls (incidence rate per person-years, 1.6 vs 0.3). For dementia subtypes, frontotemporal dementia had the highest risks of unintentional injuries (HR 4.28, 95% CI 2.80-6.52) and falls (HR 3.83, 95% CI 1.98-7.41), whereas subjects with mixed dementia were less likely to die from suicide (HR 0.11, 95% CI 0.03-0.46) and complications of medical and surgical care (HR 0.53, 95% CI 0.40-0.70) compared to controls. CONCLUSIONS AND IMPLICATIONS: Suicide risk screening and psychiatric disorders management in early-onset dementia and early interventions for unintentional injuries and falls prevention in older dementia patients should be provided.

The joint effect between fetal growth and health behaviors on the risk of cardiovascular diseases in young adulthood.

PURPOSE: To investigate the individual and the joint effect of impaired fetal growth and adult health behaviors on the risk of cardiovascular diseases (CVDs). METHODS: A total of 15,618 individuals were included from three sub-cohorts of the Stockholm Public Health Cohort. Data on participants' birthweight and gestational age were retrieved from the Medical Birth Register. Data on the diagnoses of CVDs were extracted from the Swedish National Patient Register and the Cause of Death Register. Data on health behaviors were identified from self-reported questionnaires, and health behavioral profile was defined based on the recommendations of the American Health Association. The associations of fetal growth and health behaviors with the risk of CVDs were analyzed using Cox proportional hazard model. RESULTS: Individuals born small for gestational age (SGA) had a higher risk of CVDs than those born appropriate for gestational age (AGA), and the adjusted hazard ratio (HR) and 95% confidence interval (CI) was 1.88 (1.44, 2.47). Participants born SGA and having poor health behavioral profile in adulthood had a higher risk of CVDs than those born AGA and having ideal health behaviors with adjusted HR (95% CI) being 3.58 (1.95, 6.56). CONCLUSIONS: Impaired fetal growth was associated with an increased risk of CVDs in adulthood, and the risk was highest in individuals with both impaired fetal growth and poor health behaviors in adulthood.

Construction of a new complete growth reference for urban Chinese children.

BACKGROUND: Growth chart is a valuable clinical tool to monitor the growth and nutritional status of children. A growth chart widely used in China is based on the merged data sets of national surveys in 2005. We aimed to establish an up-to-date, complete growth curve for urban Chinese children and adolescents with a full range of ages. METHODS: Using data collected in a large-scale, cross-sectional study (Prevalence and Risk factors for Obesity and Diabetes in Youth (PRODY), 2017-2019), we analyzed 201,098 urban children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that are geographically representative of China. All participants underwent physical examinations. Sex-specific percentiles of height-for-age and weight-for-age were constructed by Generalized Additive Models for Location Scale and Shape (GAMLSS) model. We also compared the median values of height-for-age or weight-for-age between our growth chart and the established growth reference using Welch-Satterthwaite T-Test. RESULTS: Consistent with the established growth reference, we observed that the P50 percentile of height-for-age reached plateaus at the age of 15 years (172 cm) and 14 years (160 cm) for boys and girls, respectively. In addition, boys aged 10 ~ 14 years and girls aged 10 ~ 12 years exhibited the most dramatic weight difference compared to those of other age groups (19.5 kg and 10.3 kg, respectively). However, our growth chart had higher median values of weight-for-age and height-for-age than the established growth reference with mean increases in weight-for-age of 1.36 kg and 1.17 kg for boys and girls, respectively, and in height-for-age of 2.9 cm and 2.6 cm for boys and girls, respectively. CONCLUSIONS: Our updated growth chart can serve as a reliable reference to assess the growth and nutritional status in urban Chinese children throughout the entire childhood.

Neutralization Activity against SARS-CoV-2 Variants after Booster Vaccination in Populations without COVID-19: A Meta-Analysis.

A number of SARS-CoV-2 variants that have evolved to have significant immune escape have emerged worldwide since the COVID-19 outbreak. The efficacy of prime vaccination is waning with the evolution of SARS-CoV-2, and the necessity of booster doses is more and more prominent. Therefore, this study aimed to compare the neutralization activity against the wild type and variants (Beta, Delta, and Omicron) in different prime-boost vaccination regimens. Electronic databases including PubMed, the Cochrane Library, Embase, medRxiv, Wanfang and CNKI were used to retrieve original studies. A total of 16 studies, 9 prime-boost vaccination regimes, and 3134 subjects were included in the meta-analysis and random effect models were used to estimate pooled neutralization titers. The neutralization activity against SARS-CoV-2 showed a significant decline with the evolution of the virus, especially in the populations primed with inactivated vaccines. For homologous immunization, only the populations boosted with mRNA vaccines consistently had a significant rise in neutralization titers (Beta: MD = 0.97; Delta: MD = 1.33; Omicron: MD = 0.74). While the heterologous immunization was more effective, the increment of neutralization titers against wild type, Beta, Delta and Omicron was 1.65 (95% CI: 1.32-1.96), 1.03 (95% CI: 0.53-1.54), 1.46 (95% CI: 1.07-1.85) and 1.15 (95% CI: 0.68-1.61), respectively. With the evolution of SARS-CoV-2, the effectiveness of prime immunization is waning. Although the administration of the booster dose could ameliorate the neutralization titers, homologous immunization regimens were gradually losing their effectiveness. Therefore, a heterologous booster dose is required, especially in populations primed with inactivated vaccines.

The Association of Vitamin D and Its Pathway Genes' Polymorphisms with Hypertensive Disorders of Pregnancy: A Prospective Cohort Study.

Objective: We aimed to explore the effect of single nucleotide polymorphism (SNP) in the genes of the vitamin D (VitD) metabolic pathway and its interaction with VitD level during pregnancy on the development of hypertensive disorders of pregnancy (HDP). Methods: The study was conducted in the Zhoushan Maternal and Child Health Care Hospital, China, from August 2011 to May 2018. The SNPs in VitD metabolic pathway-related genes were genotyped. Plasma 25-hydroxyvitamin vitamin D (25(OH)D) levels was measured at first (T1), second (T2), and third (T3) trimesters. The information of systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the diagnosis of HDP were extracted from the electronic medical record system. Multivariable linear and logistic regression models and crossover analysis were applied. Results: The prospective cohort study included 3699 pregnant women, of which 105 (2.85%) were diagnosed with HDP. After adjusting for potential confounders, VitD deficiency at T2, as well as the change of 25(OH)D level between T1 and T2, were negatively associated with DBP at T2 and T3, but not HDP. Polymorphisms in CYP24A1, GC, and LRP2 genes were associated with blood pressure and HDP. In addition, VitD interacted with CYP24A1, GC, and VDR genes' polymorphisms on blood pressure. Furthermore, participants with polymorphisms in CYP24A1-rs2248137, LRP2-rs2389557, and LRP2-rs4667591 and who had VitD deficiency at T2 showed an increased risk of HDP. Conclusions: The individual and interactive association between VitD deficiency during pregnancy and SNPs in the genes of the VitD metabolic pathway on blood pressure and HDP were identified.

Association of Vitamin D in Different Trimester with Hemoglobin during Pregnancy.

The association between vitamin D and hemoglobin has been suggested. Vitamin D can affect erythropoiesis by the induction of erythroid progenitor cell proliferation and enhance iron absorption by regulating the iron-hepcidin-ferroportin axis in monocytes. However, this relationship in pregnant women is scarce. The purpose of this study was to investigate the association between plasma vitamin D levels with hemoglobin concentration in pregnant women considering each trimester and iron supplementation. The data were obtained from Zhoushan Pregnant Women Cohort, collected from 2011 to 2018. Plasma 25(OH)D was measured in each trimester using liquid chromatography−tandem mass spectrometry. Generalized estimating equations and multiple linear regressions were performed. Finally, 2962 pregnant women and 4419 observations in the first trimester were included in this study. Plasma 25(OH)D in first trimester (T1) (ß = 0.06, p = 0.0177), second trimester (T2) (ß = 0.15, p < 0.0001), and third trimester (T3) (ß = 0.12, p = 0.0006) were positively associated with Hb. Association between plasma 25(OH)D levels in T1 and Hb concentration was positively associated with gestational age (ß = 0.005, p = 0.0421). Pregnant women with VD deficiency in T1 (OR = 1.42, 95% CI: 1.07−1.88) or T2 (OR = 1.94, 95% CI: 1.30−2.89) presented an increased risk of anemia, compared with women without VD deficiency. Moreover, the significant relationship between VD and Hb was only observed among women with iron supplementation during pregnancy. Plasma 25(OH)D levels in each trimester were positively associated with Hb concentration. Iron supplementation might be an important factor affecting the relationship between VD and Hb.

The Associations of Maternal Hemoglobin Concentration in Different Time Points and Its Changes during Pregnancy with Birth Weight Outcomes.

Maternal hemoglobin (Hb) is related to nutritional status, which affects neonatal birth weight. However, it is very common for maternal Hb to fluctuate during pregnancy. To evaluate the associations of maternal Hb in different time points and its changes during pregnancy with neonatal birth weight, small for gestational age (SGA)/low birth weight (LBW) and large for gestational age (LGA)/macrosomia, we conducted this study by using data from the Electronic Medical Record System (EMRS) database of Zhoushan Maternal and Child Care Hospital in Zhejiang province, China. The pregnancy was divided into five periods: first, early-second, mediate-second, late-second, early-third and late-third trimesters; we further calculated the maternal Hb changes during pregnancy. Overall, the socio-demographic characteristics, health-related information and childbirth-related information of 24,183 mother−infant pairs were obtained. The average Hb concentration during the different periods were 123.95 ± 10.14, 117.95 ± 9.84, 114.31 ± 9.03, 113.26 ± 8.82, 113.29 ± 8.68 and 115.01 ± 8.85 g/L, respectively. Significant dose−response relationships between maternal Hb and birth weight were observed in the first, late-second and later trimesters (p non-linear < 0.05). Maternal Hb < 100 g/L was related to a high risk of LGA/macrosomia in the late-second (OR: 1.47, 95% CI: 1.18, 1.83) and later trimesters; additionally, high maternal Hb (>140 g/L) increased the risk of SGA/LBW in the first (OR: 1.26, 95% CI: 1.01, 1.57) and late-third trimesters (OR: 1.96, 95% CI: 1.20, 3.18). In addition, the increase in maternal Hb from the late-second to late-third trimesters had a positive correlation with SGA/LBW. In conclusion, maternal Hb markedly fluctuated during pregnancy; the negative dose−response association of maternal Hb in the late-second and third trimesters, and Hb change during pregnancy with neonatal birth weight outcomes were observed, respectively. Furthermore, the phenomenon of high Hb in the first trimester and after the late-second trimester and the increase of maternal Hb from the late-second to late-third trimesters more significantly increasing the risk of SGA/LBW should especially be given more attention. Its biological mechanism needs to be further explored.

Immunogenicity and Safety of Homologous and Heterologous Prime-Boost Immunization with COVID-19 Vaccine: Systematic Review and Meta-Analysis.

A prime-boost strategy of COVID-19 vaccines brings hope to limit the spread of SARS-CoV-2, while the immunogenicity of the vaccines is waning over time. Whether a booster dose of vaccine is needed has become a widely controversial issue. However, no published meta-analysis has focused on the issue. Therefore, this study assessed the immunogenicity and safety of the different combinations of prime-boost vaccinations. Electronic databases including PubMed, the Cochrane Library, Embase, medRxiv, Wanfang and CNKI were used to retrieve the original studies. A total of 28 studies, 9 combinations of prime-boost vaccinations and 5870 subjects were included in the meta-analysis, and random effect models were used to estimate pooled immunogenicity and safety. The immunity against COVID-19 after the prime vaccination waned over time, especially in the populations primed with inactivated vaccines, in which the seropositive rate of antibodies was only 28% (95% CI: 17-40%). Booster vaccination could significantly increase the antibody responses, and heterologous immunization was more effective than homologous immunization (neutralization titers: 1.65 vs. 1.27; anti-RBD IgG: 1.85 vs. 1.15); in particular, the combination of inactivated-mRNA vaccines had the highest antibody responses (neutralization titers: MRAW = 3.64, 95% CI: 3.54-3.74; anti-RBD IgG: 3.73, 95% CI: 3.59-3.87). Moreover, compared with the initial two doses of vaccines, a booster dose did not induce additional or severe adverse events. The administration of the booster dose effectively recalled specific immune responses to SARS-CoV-2 and increased antibody levels, especially in heterologous immunization. Considering the long-term immunogenicity and vaccine equity, we suggest that now, only individuals primed with inactivated vaccines require a booster dose.

Association of hypertensive disorders of pregnancy with infant growth in the first 36 months of life.

To investigate the association of chronic hypertension, gestational hypertension, and preeclampsia diseases with infant growth in the first 36 months of life, we conducted a retrospective birth cohort of 31,734 children born in Zhoushan Maternal and Child Care Hospital between January 2001 and May 2018. Birthweight, gestational age, and infant growth (weight, height, weight/height-for-age Z score, the weight gain during childhood) were the main outcomes. The associations of chronic hypertension, gestational hypertension, and preeclampsia diseases with birth outcomes and infant growth at children's age of 3, 6, 12, 18, and 24 months were analyzed by multivariable regression models. Gestational hypertension, preeclampsia diseases, and chronic hypertension were significantly associated with lower birthweight and shorter gestational age. Both gestational hypertension and preeclampsia diseases were respectively inversely associated with weight, weight-for-age Z score, height, and height-for-age Z score of children in the whole sample and sub-sample data analysis from birth to the age of 36 months, although correction for birthweight rendered the associations nonsignificant. No significant association of gestational hypertension, preeclampsia diseases, and chronic hypertension with weight gain was found. Conclusion: The inverse associations of gestational hypertension and preeclampsia diseases with infant growth in early childhood were mainly mediated by the effect of gestational hypertension and preeclampsia diseases on lower birthweight. What is Known: • Hypertensive disorders of pregnancy are associated with increased risk of adverse birth outcomes. What is New: • Both gestational hypertension and preeclampsia were respectively inversely associated with physical development of offspring from birth to the age of 36 months. • Lower birthweight might be the mediator of the inverse associations of gestational hypertension and preeclampsia diseases with infant growth in early childhood.

The Association of Gene Variants in the Vitamin D Metabolic Pathway and Its Interaction with Vitamin D on Gestational Diabetes Mellitus: A Prospective Cohort Study.

The present prospective study included 2156 women and investigated the effect of gene variants in the vitamin D (VitD) metabolic and glucose pathways and their interaction with VitD levels during pregnancy on gestational diabetes mellitus (GDM). Plasma 25(OH)D concentrations were measured at the first and second trimesters. GDM subtype 1 was defined as those with isolated elevated fasting plasma glucose; GDM subtype 2 were those with isolated elevated postprandial glucose at 1 h and/or 2 h; and GDM subtype 3 were those with both elevated fasting plasma glucose and postprandial glucose. Six Gc isoforms were categorized based on two GC gene variants rs4588 and rs7041, including 1s/1s, 1s/2, 1s/1f, 2/2, 1f/2 and 1f/1f. VDR-rs10783219 and MTNR1B-rs10830962 were associated with increased risks of GDM and GDM subtype 2; interactions between each other as well as with CDKAL1-rs7754840 were observed (Pinteraction < 0.05). Compared with the 1f/1f isoform, the risk of GDM subtype 2 among women with 1f/2, 2/2, 1s/1f, 1s/2 and 1s/1s isoforms and with prepregnancy body mass index ≥24 kg/m2 increased by 5.11, 10.01, 10, 14.23, 19.45 times, respectively. Gene variants in VitD pathway interacts with VitD deficiency at the first trimester on the risk of GDM and GDM subtype 2.

Regional Disparities in Obesity Among a Heterogeneous Population of Chinese Children and Adolescents.

Importance: Obesity is a public health challenge in China, but the geographical profiles of overweight and obesity among Chinese children are limited. Objective: To examine regional disparities in the prevalence of obesity among the heterogeneous population of Chinese children and adolescents to provide a more accurate profile of obesity among children in China. Design, Setting, and Participants: The Prevalence and Risk Factors for Obesity and Diabetes in Youth (PRODY) study was a cross-sectional survey study conducted from January 1, 2017, to December 31, 2019, among 201 098 children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that produced a sample of Chinese children with a full range of ages and wide geographical coverage using a multistage, stratified, cluster-sampling design. Exposures: Five regions geographically representative of China (northern, eastern, southern, western, and central). Main Outcomes and Measures: The body weights and heights of all participants were measured. Multilevel, multinomial logistic regression models were used to estimate the prevalence of overweight and obesity. Results: Among 201 098 healthy children (105 875 boys [52.6%]; mean [SD] age, 9.8 [3.8] years) from eastern, southern, northern, central, and western China, the highest obesity prevalence was estimated for children aged 8 to 13 years in northern China (from 18.8% [95% CI, 16.2%-21.7%] to 23.6% [95% CI, 20.5%-26.9%]) and for boys aged 3 to 6 years in western China (from 18.1% [95% CI, 10.4%-29.4%] to 28.6% [95% CI, 14.3%-49.0%]). Boys had a higher prevalence than girls of obesity only in eastern and northern China, with a mean difference in prevalence of 4.6% (95% CI, 3.8%-5.4%) and 7.6% (95% CI, 6.5%-8.6%), respectively. Conclusions and Relevance: In this survey study, substantial geographic disparities in the prevalence of obesity and overweight were found among the heterogeneous population of Chinese children. The results suggest that special attention should be paid to vulnerable children and that regionally adapted interventions are needed to efficiently mitigate obesity in children.

Association of vitamin D and gene variants in the vitamin D metabolic pathway with preterm birth.

OBJECTIVES: The aim of this study was to explore the association of vitamin D (VitD) levels during pregnancy and its metabolic pathway genes with the risk for preterm birth (PTB) among pregnant women in southeast China. METHODS: This study was conducted in Zhoushan Maternal and Child Health Hospital, Zhejiang, from August 2011 to May 2018. Plasma 25-hydroxyvitamin vitamin D [25(OH)D] levels in three trimesters and single-nucleotide morphisms in the VitD metabolic pathway were measured. Relevant information was collected using questionnaires and an electronic medical recorder system. Multiple statistical methods including linear regression, logistic regression, and crossover analysis were applied. RESULTS: The prospective cohort study included 3465 pregnant women, of which 202 were PTB (week of gestation at delivery: 33.38 ± 4.05), accounting for 5.8%. After adjusting for potential confounders, VitD sufficiency (≥30 ng/mL) in the second and third trimesters was associated with longer gestational age at delivery compared with VitD deficiency (<20 ng/mL). However, no significant association was found between VitD with the risk for PTB. rs7041, rs10210408, and rs2228171 were associated with gestational week and the risk for PTB. Significant associations were found of rs10210408, rs2209314, rs1155563, rs2544381 and the status of VitD in the second and third trimester with the gestational week. We also found that rs7041 and VitD in the second trimester might exert interaction on gestational week and the risk for PTB (Pinter = 0.038; Pinter = 0.019); rs16846876 and VitD in the second trimester might exert interaction on gestational week (Pinter = 0.024); rs4334089 and VitD in the third trimester might exert interaction on gestational week (Pinter = 0.024). Similar results were found when we tested pregnant women's plasma 25(OH)D in the first and second trimesters. CONCLUSIONS: Women with VitD deficiency were associated with shorter gestational weeks. Single-nucleotide morphisms in VitD metabolic pathway genes were significantly associated with gestation week and the risk for PTB, mainly in vitamin D-binding protein (GC) and low-density lipoprotein-related protein 2 (LRP2)genes. Additionally, maternal VitD with GC gene and maternal VitD with vitamin D receptor (VDR) gene might exert interactions on the risk for PTB.

Efficacy and Safety of COVID-19 Vaccines in Phase III Trials: A Meta-Analysis.

Nowadays, the vaccination with COVID-19 vaccines is being promoted worldwide, professionals and common people are very concerned about the efficacy and safety of COVID-19 vaccines. No published systematic review and meta-analysis has assessed the efficacy and safety of the COVID-19 vaccines based on data from phase III clinical trials. Therefore, this study has estimated the efficacy and safety of COVID-19 vaccines and the differences between vaccine types. PubMed, Embase, the Cochrane Library, CNKI, Wanfang, medRxiv databases and two websites were used to retrieve the studies. Random-effects models were used to estimate the pooled efficacy and safety with risk ratio (RR). A total of eight studies, seven COVID-19 vaccines and 158,204 subjects were included in the meta-analysis. All the vaccines had a good preventive effect on COVID-19 (RR = 0.17, 95% CI: 0.09-0.32), and the mRNA vaccine (RR = 0.05, 95% CI: 0.03-0.09) was the most effective against COVID-19, while the inactivated vaccine (RR = 0.32, 95% CI: 0.19-0.54) was the least. In terms of safety, the risk of overall adverse events showed an increase in the vaccine group after the first (RR = 1.46, 95% CI: 1.03-2.05) or second (RR = 1.52, 95% CI: 1.04-2.20) injection. However, compared with the first injection, the risk of local (RR = 2.64, 95% CI: 1.02-6.83 vs. RR = 2.25, 95% CI: 0.52-9.75) and systemic (RR = 1.33, 95% CI: 1.21-1.46 vs. RR = 1.59, 95% CI: 0.84-3.01) adverse events decreased after the second injection. As for the mRNA vaccine, the risk of overall adverse events increased significantly, compared with the placebo, no matter whether it was the first (RR = 1.83, 95% CI = 1.80-1.86) or the second (RR = 2.16, 95% CI = 2.11-2.20) injection. All the COVID-19 vaccines that have published the data of phase III clinical trials have excellent efficacy, and the risk of adverse events is acceptable. The mRNA vaccines were the most effective against COVID-19, meanwhile the risk and grade of adverse events was minimal, compared to that of severe symptoms induced by COVID-19.

Association of nausea and vomiting of pregnancy with infant growth in the first 24 months of life.

PURPOSE: We aimed to investigate the association of maternal nausea and vomiting during pregnancy (NVP) with infant growth in the first 24 months of life and compare the effect of fetal gender. METHODS: This prospective cohort study was conducted in Zhoushan Maternal and Child Health Hospital, Zhejiang, from 2011 to 2018. 1942 pairs of singleton newborns and their mothers were selected as participants. Main outcomes were gestational weight gain (GWG), birth outcomes (birthweight and gestational age) and infant growth [weight, height, weight/height-for-age Z score (WAZ/HAZ), the weight gain during childhood]. The associations of NVP with birth outcomes and infant growth at children's age of 1, 3, 6, 12, 18, and 24 months were analyzed by multivariable regression models. RESULTS: Of the 1942 women, 1395 had NVP at first trimester (T1) and among them, 210 still experienced NVP at second trimester (T2). Compared with women without NVP, women experienced severe NVP at T1 were related with lower total GWG. Mild and moderate NVP at T1 were negatively associated with lower birthweight among women with male infants. Female infants exposed to maternal NVP at T1, especially for severe degree, were showed greater weight, WAZ, height, HAZ, and weight gain after 1 year old (at age of 12, 18, 24 months). No association between maternal NVP and infant growth was observed among male infants. CONCLUSION: Exposure to NVP at T1 was, respectively, associated with lower GWG. Favorable influence of NVP at T1 on infant growth was observed among female offspring.

Association of vitamin D pathway gene polymorphisms with vitamin D level during pregnancy was modified by season and vitamin D supplement.

BACKGROUND & AIMS: This study aims to explore the associations of vitamin D (VD) metabolic pathway gene with 25(OH)D level in pregnant women and the interactions of SNP with season and VD supplement. METHODS: A total of 2658 pregnant women were selected from Zhoushan Pregnant Women Cohort study. Gestational 25(OH)D level and single nucleotide polymorphism (SNP) of VD metabolic pathway gene were detected. Multilinear regression models were used to estimate associations of SNPs with gestational 25(OH)D levels. Stratified analyses were performed to test the interactions of SNP with season and VD supplements. RESULTS: The mutations of rs2298849 and rs7041 on the GC gene were respectively associated with higher 25(OH)D in the first and third trimester; the mutations of seven SNPs (rs1155563, rs16846876, rs17467825, rs2282679, rs2298850, rs3755967, and rs4588) on the GC gene were respectively associated with lower 25(OH)D both in the first and third trimester, and lower changes in 25(OH)D during late pregnancy. The mutations of above seven SNPs, except for rs1155563, were also respectively associated with lower 25(OH)D in the second trimester, but to a lesser extent; Besides, pregnant women with mutation on CYP24A1-rs2209314 had a higher increment in 25(OH)D than their counterparts in the second trimester. The increasing dose effect of Gc isoform on 25(OH)D was observed. The associations of GC and LRP2 genes with 25(OH)D modified by season and VD supplements. CONCLUSIONS: The polymorphisms of VD metabolic pathway gene were associated with gestational 25(OH)D, and the associations differ by seasons and VD supplements. Gc isoform exerted a profound influence on gestational 25(OH)D.