Hippocampal volume mediates the association of arterial stiffness with cognitive impairment in adult population.

OBJECTIVES: To investigate the association of arterial stiffness with brain perfusion, brain tissue volume and cognitive impairment in the general adult population. MATERIALS AND METHODS: This prospective study included 1488 adult participants (age range: 22.8-83.9 years) from the Kailuan study. All participants underwent brachial-ankle pulse wave velocity (PWV) measurement, brain MRI, and Montreal Cognitive Assessment (MoCA). The association of PWV with cerebral blood flow (CBF), brain tissue volume and MoCA score was investigated. Mediation analysis was used to determine whether CBF and brain tissue volume changes mediated the associations between PWV and MoCA score. RESULTS: A 1 standard deviation (SD) increase in PWV was associated with lower total brain CBF [ß (95% CI) -0.67 (-1.2 to -0.14)], total gray matter CBF [ß (95% CI) -0.7 [-1.27 to -0.13)], frontal lobe CBF [ß (95% CI) -0.59 (-1.17 to -0.01)], parietal lobe CBF [ß (95% CI) -0.8 (-1.43 to -0.18)], and temporal lobe CBF [ß (95% CI) -0.68 (-1.24 to -0.12)]. Negative associations were found for PWV and total brain volume [ß (95% CI) -4.8 (-7.61 to -1.99)] and hippocampus volume [ß (95% CI) -0.08 (-0.13 to -0.04)]. A 1 SD increase PWV was significantly associated with elevated odds of developing cognitive impairment [odds ratio (95% CI) 1.21 (1.01-1.45)]. Mediation analysis showed that hippocampal volume partially mediated the negative association between PWV and MoCA scores (proportion: 14.173%). CONCLUSION: High arterial stiffness was associated with decreased total and regional CBF, brain tissue volume, and cognitive impairment. Hippocampal volume partially mediated the effects of arterial stiffness on cognitive impairment.

Prenatal maternal stress, sleep quality, and neonatal birth weight: A prospective cohort study.

To assess if the impacts of prenatal maternal stress (PNMS) on neonatal physical development including birth weight and body length vary by trimesters, and to explore the mediating effect of sleep quality in the relationships. A total of 2778 pregnant women were included from the Shanghai Maternal-Child Pairs Cohort. PNMS and sleep quality were measured in the first trimester (12-16 gestational weeks) and third trimester (32-36 gestational weeks) using the Life Event Scale for Pregnant Women (LESPW) and Pittsburgh Sleep Quality Index, respectively. And total LESPW scores were classified into three groups: high stress (≥75th percentile), medium stress (≥25th and <75th percentile), and low stress (<25th percentile). Multiple linear and logistic regressions were employed to examine the associations between PNMS and birth weight, and bootstrap were utilized to explore the mediating effects of maternal sleep. Higher (adjusted odds ratio, aOR = 1.521; 95% confidence interval (CI), 1.104-2.096) and medium (aOR = 1.421; 95% CI, 1.071-1.885) PNMS and stress from subjective events (aOR = 1.334; 95% CI, 1.076-1.654) in the first trimester were significantly associated with elevated risk for large for gestational age. Maternal severe negative objective events stress (OE3) in the third trimester were negatively associated with birth weight (ß = -0.667; 95% CI, -1.047∼-0.287), and maternal sleep latency during this period acted as a mediator in the association (indirect effect: ß = -0.0144; 95% CI, -0.0427∼-0.0003). Besides, a significant negative correlation between total LESPW score (ß = -0.022; 95% CI, -0.038∼-0.006; per 100 score) and body length in the third trimester was also observed. The impact of PNMS on neonatal birth weight varies by stress types and exposure timing. Prolonged maternal sleep latency in the third trimester correlated with lower birth weight, and mediating the link of OE3 and birth weight, which might indicate a critical period of vulnerability to the effects of PNMS on neonatal physical development.

Serum uric acid is associated with midbrain enlarged perivascular spaces: Results from Multi-modality Medical imaging sTudy bAsed on KaiLuan Study (META-KLS).

BACKGROUND: Serum uric acid (SUA) is a major cause of cardiovascular and cerebrovascular diseases. Whether and to what extent the excess risk of enlarged perivascular spaces (EPVS) conferred by SUA is unknown. The study was conducted to investigate the association between SUA and EPVS in different brain regions. METHODS: Data are from Multi-modality medical imaging study based on Kailuan study (META-KLS) in this cross-sectional study. Participants were divided into five groups based on SUA levels, and EPVS in basal ganglia (BG), centrum semiovale (CSO) and midbrain (MB) was systematically assessed and divided into Low and High group. Odds ratio (OR) and 95% confidence intervals (95% CIs) for high EPVS outcomes were estimated using multivariable logistic regression analysis. Restricted cubic spline (RCS) was used to further investigate dose-response relationship. RESULTS: A total of 1014 participants aged 25-83 years from 11 centers were enrolled in the study. In the multivariable-adjusted model, SUA, as an independent risk factor, correlated positively with high degree of MB-EPVS (OR, 1.002; 95% CI, 1.000 to 1.004; p = 0.023) in general population. In addition, RCS further demonstrated the linear association between SUA and MB-EPVS (p = 0.072). No association was found between SUA and BG-EPVS or CSO-EPVS. CONCLUSION: SUA was an independent risk factor of MB-EPVS. High SUA levels were more predictive of increased risk occurrence of high degree of MB-EPVS, supporting a linear association between SUA and MB-EPVS and further indicating that SUA may play an important role in cerebral small vessel disease. TRIAL REGISTRATION: The KaiLuan Study and META-KLS were registered online (ChiCTR2000029767 on chictr.org.cn and NCT05453877 on Clinicaltrials.gov, respectively).

Prenatal organophosphate esters exposure and neurodevelopment trajectory in infancy: Evidence from the Shanghai Maternal-Child Pairs Cohort.

BACKGROUND: Concerns remain about the neurotoxic properties of the ubiquitous organophosphate esters (OPEs), the replacement of the toxicant polybrominated diphenyl ethers. OBJECTIVES: We examined the associations of prenatal exposure to OPEs and their mixtures with early-life neurodevelopment trajectories. METHODS: Totally 1276 mother-child pairs were recruited from the Shanghai Maternal-Child Pairs Cohort. A high-performance liquid chromatography-triple quadrupole mass spectrometer was used to measure the levels of 7 OPEs in cord serum. Ages and Stages Questionnaires was used to examine children's neuropsychological development at 2, 6, 12, and 24 months of age. Group-based trajectory models were applied to derive the neurodevelopmental trajectories. Multiple linear regression and logistic regression model were performed to assess the relationships between OPEs exposure and neurodevelopment and trajectories. Mixtures for widely detected OPEs (n = 4) were investigated using quantile-based g-computation. RESULTS: Tributyl phosphate (TBP), tris (2-butoxy ethyl) phosphate (TBEP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and 2-ethylhexyl diphenyl phosphate (EHDPP), had detection rates >50 %. TDCPP had the highest median concentration (1.02 µg/L) in cord serum. EHDPP concentrations were negatively associated with scores in most domains at 12 months of age, with effect values (ß) ranging from -1.89 to -0.57. EHDPP could negatively affect the total ASQ (OR = 1.07, 95 % CI: 1, 1.15) and gross-motor (OR = 1.09, 95 % CI: 1.02, 1.17) trajectory in infancy. Joint exposure to OPEs was associated with decreased scores in the total ASQ, gross-motor, fine-motor and problem-solving domain of 12-month-old infants, with ß ranging from -5.93 to -1.25. In addition, the qgcomp models indicated significant positive associations between the concentrations of OPEs mixtures and risks of the persistently low group of the total ASQ, gross-motor and fine-motor development in early childhood. The impact of OPEs was more pronounced in boys. DISCUSSION: Our findings suggested OPEs, especially EHDPP, had a persistently negative effect on neurodevelopment during the first 2 years.

Barriers and facilitators to using ophthalmic clinical health services following school vision screening: a mixed-methods study.

OBJECTIVE: To identify determinants of the utilisation of ophthalmic clinical health services among students who failed school vision screening. METHODS: This study employed a sequential explanatory mixed methods design, underpinned by Andersen's Behavioural Model of Health Service Utilisation. Data were initially gathered through interviews with 27 stakeholders-comprising 5 ophthalmologists, 7 community doctors, 7 public health professionals and 8 teachers. The qualitative insights informed the construction of a questionnaire, which subsequently garnered responses from 6215 participants. Qualitative data underwent thematic analysis with NVivo V.12, while quantitative data were analysed using multivariable multinomial logistic regression in SAS V.9.4. Data integration was performed using the Pillar Integration Process for a deductive, evidence-based synthesis of findings. RESULTS: The research revealed that students attending vision demonstration schools and receiving encouragement from schools or communities to access clinical ophthalmic services demonstrated higher adherence to referral (OR=1.66, 95% CI 1.30 to 2.12; OR=1.54, 95% CI 1.33 to 1.80). Conversely, older students and those from higher-income families exhibited lower adherence rates (OR=0.31, 95% CI 0.23 to 0.44; OR=0.34, 95% CI 0.25 to 0.46). Moreover, students with less urgent medical needs were more likely to adhere to referrals compared with those needing immediate referrals (OR=1.24, 95% CI 1.06 to 1.45).Four pillars emerged: (a) adherence decreased with age, (b) financial constraints did not pose an obstacle, (c) public health services played a critical role, (d) referral urgency did not linearly correlate with adherence. CONCLUSION: The utilisation of ophthalmic clinical health services following vision screening failure in students is significantly influenced by public health services provided by schools or communities, such as prompting those with abnormal screening results to access ophthalmic clinical health services.

Prenatal PFAS exposure, gut microbiota dysbiosis, and neurobehavioral development in childhood.

Studies on the role of the gut microbiota in the associations between per- and polyfluoroalkyl substance (PFAS) exposure and adverse neurodevelopment are limited. Umbilical cord serum and faeces samples were collected from children, and the Strengths and Difficulties Questionnaire (SDQ) was conducted. Generalized linear models, linear mixed-effects models, multivariate analysis by linear models and microbiome regression-based kernel association tests were used to evaluate the associations among PFAS exposure, the gut microbiota, and neurobehavioural development. Perfluorohexane sulfonic acid (PFHxS) exposure was associated with increased scores for conduct problems and externalizing problems, as well as altered gut microbiota alpha and beta diversity. PFHxS concentrations were associated with higher relative abundances of Enterococcus spp. but lower relative abundances of several short-chain fatty acid-producing genera (e.g., Ruminococcus gauvreauii group spp.). PFHxS exposure was also associated with increased oxidative phosphorylation. Alpha and beta diversity were found significantly associated with conduct problems and externalizing problems. Ruminococcus gauvreauii group spp. abundance was positively correlated with prosocial behavior scores. Increased alpha diversity played a mediating role in the associations of PFHxS exposure with conduct problems. Our results suggest that the gut microbiota might play an important role in PFAS neurotoxicity, which may have implications for PFAS control.

Experiences and perspectives of nurses infected with COVID-19: A qualitative systematic review and meta-synthesis.

This qualitative systematic review aims to comprehensively understand the experiences and perspectives of nurses infected with COVID-19, addressing a significant gap in the current literature. Following the JBI meta-synthesis approach, a rigorous search was conducted across nine electronic databases and references until January 16, 2023. Seventeen eligible studies underwent quality assessment using the JBI critical checklist. Data were synthesized using standardized tools, and the ConQual tool evaluated confidence in the findings. Seven key findings emerged, providing valuable insights into emotional experiences, adaptation to COVID-19 challenges, influence of support systems, coping strategies, posttraumatic growth perceptions, and effects on professional identity and career advancement. The findings highlight emotional toll, adaptive strategies, and professional implications for nurses. Moreover, they emphasize the importance of support systems, coping mechanisms, and posttraumatic growth in promoting nurses' well-being and resilience. These insights have practical implications for targeted interventions and support mechanisms to enhance infected nurses' well-being and improve healthcare outcomes.

Prospective Association between Total and Trimester-Specific Gestational Weight Gain Rate and Physical Growth Status in Children within 24 Months after Birth.

In this study, our aim was to investigate the potential correlation between the mother's total gestational weight gain (GWG) rate and the trimester-specific GWG rate (GWGR) with the physical development status of the child within 24 months of age. We utilized linear regression models and linear mixed effects models to explore both time point and longitudinal relationships between GWGR and children's anthropometric outcome z-scores at 0, 1, 2, 4, 6, 9, 12, 18, and 24 months. To examine the critical exposure windows, we employed multiple informant models. We also conducted a stratified analysis considering pre-pregnancy BMI and the gender of the children. Our findings revealed notable positive associations between total GWGR and z-scores for body mass index for age (BMIZ), head circumference for age (HCZ), weight for age (WAZ), length for age (LAZ), and weight for length (WHZ) across different trimesters of pregnancy (pint < 0.05). The GWGR during the first two trimesters mainly influenced the relationship between total GWGR and BMIZ, WAZ, and LAZ, while the GWGR during the first trimester had a significant impact on the correlation with HCZ (0.206, 95% CI 0.090 to 0.322). Notably, the associations of GWGR and children's BMIZ were pronounced in male children and pre-pregnancy normal-weight women. In conclusion, our study findings indicated that a higher GWGR during each trimester was associated with greater physical growth during the first 24 months of life, especially GWGR in the first and second trimesters.

Co-exposure to organic UV filters and phthalates and their associations with oxidative stress levels in children: A prospective follow-up study in China.

Children are highly vulnerable to environmental pollutants, especially endocrine-disrupting chemicals (EDCs). Previous research has linked both organic UV filters and phthalates exposure to adiposity and pubertal development in children. Nevertheless, the individual and collective effects of these chemicals on this population remain poorly understood. In this study, twelve organic UV filters and metabolites, six phthalate metabolites and two oxidative stress biomarkers were analyzed in a prospective follow-up study in Shanghai, China after a baseline study conducted 1.5 years earlier. Results revealed a positive association between exposure to individual organic UV filters or their mixture and levels of 8-OHdG (ß ranging from 0.242 to 0.588, P < 0.05), a marker of oxidative DNA damage. BP-3 and OD-PABA made a greater contribution to oxidative DNA damage than other UV filters. Levels of 8-OHdG were also positively correlated with single phthalate metabolites and their mixture, with MnBP and MMP contributing the most. Stratified analysis found that these associations were mainly observed in girls. Our mixture analysis revealed cumulative risks of oxidative DNA damage when there was co-exposure to these two kinds of EDCs. These results underscore the importance of considering the risks associated with organic UV filters and the necessity of evaluating the effects of all these pollutants, both individually and in mixtures.

Breastfeeding is associated with reduced risks of central obesity and hypertension in young school-aged children: a large, population-based study.

BACKGROUND: Previous studies examined the effects of breastfeeding on measured values of body circumferences or blood pressure during childhood. However, limited data are available for the association between child feeding and a specific disease diagnosed as central obesity or hypertension. Hence, we aimed to examine whether the type and duration of breastfeeding are associated with obesity/central obesity or hypertension in young school-aged children. METHODS: We matched the data obtained from a cross-sectional survey in 2019 with retrospective breastfeeding information recorded in the database. Heights, weights, waist circumferences, and blood pressures of 8480 children in first grade of primary schools in Shanghai, China were measured to diagnose obesity, central obesity, and hypertension. Data on child feeding was collected retrospectively from clinical records. Associations between the type/duration of breastfeeding and children's measured values of body mass index, waist circumference, and blood pressure were analysed by linear regression. Associations between the type/duration of breastfeeding and risks of obesity, central obesity, and hypertension were analysed by generalised linear models. RESULTS: Breastfeeding duration was inversely associated with blood pressure values in children in the first grade. Each month's increase in the duration of any breastfeeding was associated with a 0.07 mmHg decrease in systolic blood pressure (P < 0.01) and a 0.05 mmHg decrease in diastolic blood pressure (P < 0.01). Any breastfeeding > one month was associated with a reduced risk of hypertension (adjusted risk ratio 0.84; 95% CI 0.73, 0.96, P = 0.01). Exclusive breastfeeding > one month was associated with a reduced risk of central obesity (adjusted risk ratio 0.76; 95% CI: 0.60, 0.96, P = 0.02). Any breastfeeding > 12 months was linked with a lower risk of hypertension (adjusted risk ratio 0.83; 95% CI 0.70, 0.98, P = 0.03). CONCLUSIONS: Lack of breastfeeding is associated with higher risks of central obesity and hypertension during middle childhood. As a potential component of the public health strategy to reduce population levels of metabolic and cardiovascular diseases, breastfeeding could be a vital prevention strategy.

Effects of school myopia management measures on myopia onset and progression among Chinese primary school students.

BACKGROUND: Schools play an organizational role in managing myopia-related behavioral habits among students. We evaluated the effects of school myopia management measures on myopia onset and progression in a school-based prospective 1-year observational study. METHODS: In total, 8319 children from 26 elementary schools were included. Online questionnaire completed by a parent, in which school myopia management experience including outdoor activities in recess or physical education class, teachers' supervision, and teaching facilities. Variables were defined as implemented well or poorly, according to the Comprehensive Plan to Prevent Myopia among Children and Teenagers. Children underwent ophthalmic examinations, and the incidence and progression of myopia from 2019 to 2020 were estimated. Multilevel logistic regression models were constructed to analyze the association between school management measures and myopia development in 8,9 years and 10,11 years students. RESULTS: From 2019 to 2020, the incidence of myopia among primary school students was 36.49%; the mean difference of spherical equivalent in myopic children was - 0.29 ± 1.22 diopters. The risk of incident myopia was reduced by 20% in 8,9 years participants with well-implemented class recess compared with those with poorly implemented class recess (adjusted odds ratio [aOR]: 0.80, p = 0.032). PE outdoor time was significantly associated with myopia incidence in 10,11 years students (aOR: 0.76, p = 0.043). Compared with poorly implemented reading and writing posture, desk and chair height, 10,11 participants with well-implemented desk and chair height were less likely to have rapid myopic progression (p = 0.029, p = 0.022). CONCLUSION: In Shanghai, children's myopia is associated with better implementation of school myopia management measures. The present findings suggest that outdoor activities during class recess or PE class, providing suitable desks and chairs, and adequate instruction in reading and writing postures might protect against pathological eye growth. An age-specific myopia prevention and control programs in school is of primary importance.

Enlarged Perivascular Spaces in Relation to Cumulative Blood Pressure Exposure and Cognitive Impairment.

BACKGROUND: Hypertension and enlarged perivascular spaces (EPVS) are thought to be associated with cognitive impairment. However, the correlations among hypertension, EPVS, and cognitive impairment have not been studied yet. We aimed to investigate the relationships between cumulative blood pressure (cBP) exposure with EPVS and cognitive impairment and whether EPVS may mediate the relationship between cBP and cognitive impairment. METHODS: A total of 1507 subjects from the Kailuan prospective cohort study were enrolled. cBP was calculated from 2006 to 2022. The effects of cBP, EPVS scores, and cognitive impairment were evaluated using a logistic regression model. The relationships among cBP, EPVS score, and cognitive impairment were analyzed using a mediation model. RESULTS: An increase in cBP was positively correlated with an increase in EPVS score. For every SD increase in cBP, the odds ratios (95% CI) of increased EPVS score of the centrum semiovale were 1.67 (1.43-1.95), 1.63 (1.4-1.9), and 1.35 (1.17-1.56), respectively; the odds ratios (95% CI) of increased EPVS score of the basal ganglia were 1.83 (1.56-2.15), 2.01 (1.7-2.36), and 1.31 (1.13-1.52), respectively; and the odds ratios (95% CI) of developing cognitive impairment were 1.28 (1.06-1.53), 1.13 (0.95-1.34), and 1.28 (1.07-1.5), respectively. Basal ganglia-EPVS score accounted for 10.46% to 18.32% of the mediating effects on the relationships of cBP/SD with cognitive impairment. CONCLUSIONS: High cBP exposure was an independent risk factor for EPVS, and basal ganglia-EPVS score mediated the effects of cBP on cognitive impairment. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: ChiCTR-TNRC-11001489.

Association of blood pressure with brain perfusion and structure: A population-based prospective study.

PURPOSE: To explore the association of blood pressure (BP) measurements with cerebral blood flow (CBF) and brain structure in general population. METHOD: This prospective study included 902 participants from Kailuan community. All participants underwent brain MRI and BP measurements. The association of BP indicators with CBF, brain tissue volume and white matter hyperintensity (WMH) volume were investigated. In addition, mediation analysis was used to determine whether significantly changed brain tissue volume explained associations between BP and CBF. RESULTS: Elevated diastolic BP (DBP), but not systolic BP (SBP), was associated with lower CBF in the total brain (ß [95 % CI]: -0.62 [-1.14, -0.10]), total gray matter (ß [95 % CI]: -0.71 [-1.27, -0.14]), hippocampus (ß [95 % CI]: -0.59 [-1.13, -0.05]), frontal (ß [95 % CI]: -0.72 [-1.31, -0.13]), parietal (ß [95 % CI]: -0.92 [-1.54, -0.3]), temporal (ß [95 % CI]: -0.63 [-1.18, -0.08]), and occipital lobe (ß [95 % CI]: -0.69 [-1.37, -0.01]). Higher SBP and DBP were associated with reduced total and regional brain tissue volume (all p < 0.05). Increased SBP and PP were associated with higher total and periventricular WMH volume (all p < 0.05). In addition, mediation analysis identified that significantly decreased brain volume did not mediate the associations of BP measurements and lower CBF in corresponding region (all p > 0.05). CONCLUSIONS: Elevated BP level was associated with decreased total and regional CBF and brain tissue volume and increased WMH burden.

Ozone Exposure During Pregnancy and Risk of Gestational Hypertension or Preeclampsia in China.

Importance: Although certain air pollutants have been associated with adverse obstetric outcomes, evidence regarding the association of ozone (O3) exposure with the risk of hypertensive disorders in pregnancy (HDP) is limited and inconsistent. Objectives: To evaluate the association between gestational O3 exposure and HDP (ie, gestational hypertension and preeclampsia) risk, and to explore the window of susceptibility for O3 exposure during pregnancy. Design, Setting, and Participants: This cohort study recruited pregnant patients from the Obstetrics and Gynecology Hospital of Fudan University in Shanghai, China, from March 2017 to December 2018. Participants were older than 18 years, had no infectious diseases or chronic noncommunicable diseases before pregnancy, were Shanghai residents with intent to participate in the study, and had plans to give birth in Shanghai. Gestational hypertension and preeclampsia were diagnosed according to the diagnostic criteria of the Chinese Society of Obstetrics and Gynecology during the study period. Data on residential addresses, demographic characteristics, and household living environments were collected from participants through a questionnaire survey. Data were analyzed from December 10, 2021, to May 10, 2022. Exposures: A high temporospatial resolution model was applied to predict individual levels of daily O3 exposure during pregnancy. Main Outcomes and Measures: The outcomes were gestational hypertension and preeclampsia, and data on these diagnoses were extracted from the hospital's information system. A logistic regression model was used to estimate the associations between O3 exposure and risk of gestational hypertension or preeclampsia. Exposure-response associations were confirmed by restricted cubic spline functions. Distributed lag models were used to identify the O3 exposure window of susceptibility. Results: Among the 7841 participants (all females; mean [SD] age, 30.4 [3.8] years), 255 (3.2%) had gestational hypertension and 406 (5.2%) had preeclampsia. Pregnant individuals with HDP had considerably higher prepregnancy body mass indexes and lower educational levels. The mean (SD) O3 exposure levels were 97.66 (25.71) µg/m3 in the first trimester and 106.13 (22.13) µg/m3 in the second trimester. Each 10-µg/m3 increment of O3 exposure during the first trimester was associated with higher gestational hypertension risk (relative risk, 1.28; 95% CI, 1.04-1.57). However, gestational O3 exposure was not associated with the risk of preeclampsia. The restricted cubic spline function analysis revealed an exposure-response association between O3 exposure and risk of gestational hypertension. Conclusions and Relevance: Results of this study showed an association between increased gestational hypertension risk and O3 exposure during the first trimester. Furthermore, gestational weeks 1 to 9 were identified as the window of susceptibility for O3 exposure and elevated gestational hypertension risk. Sustainable O3 control is needed to reduce the disease burden of gestational hypertension.

Associations of prenatal PFAS exposure and early childhood neurodevelopment: Evidence from the Shanghai Maternal-Child Pairs Cohort.

Epidemiological data on the effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) on infant neurodevelopment trajectories are far from being sufficiently addressed. In this study, 1285 mother-child pairs were recruited during 2016-2017. A high-performance liquid chromatography-triple quadrupole mass spectrometer was used to measure 16 PFAS levels in cord serum. Ages and Stages Questionnaires were used to examine children's neurodevelopment at 2, 6, 12, and 24 months of age. Group-based trajectory models were applied to derive the neurodevelopmental trajectories. Children with relatively low scores from 2 to 24 months were classified into a low-score group and were used as a risk group in each domain. Multiple linear regression, logistic regression, and quantile-based g-computation were performed to assess associations of single or mixture PFAS exposures with neurodevelopment and trajectories. Perfluorooctane sulphonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and 6:2 chlorinated polyfluorooctane ether sulfonate (6:2Cl-PFESA) were detected in over 90 % samples. PFOA had the highest concentration (median: 4.61 µg/L). Each ln-unit (µg/L) increase of PFAS (e.g., PFOA, PFOS, PFHxS, 6:2Cl-PFESA) was associated with poor scores of communication domain at 6 months, with the effect size ranging from -0.69 to -0.44. PFOS (OR: 1.14, (1.03, 1.26), PFDA (OR:1.08, (1.02, 1.15)), PFHxS (OR:1.31, (1.12, 1.56)), and 6:2Cl-PFESA (OR:1.08, (1.00, 1.16)) were associated with an increased risk of being in the low-score group in the early childhood communication domain's trajectory. Each mixture quartile increment was associated with a 1.60 (-2.76, -0.45) decrease in communication domain scores of 6-month-old infants, and the mixture effect was mainly attributed to PFOS. Each mixture quartile increase was associated with a 1.23-fold (1.03, 1.46) risk of being in the low-score group of the communication domain, and the mixture effect was mainly attributed to PFOS. In conclusion, PFAS and their mixtures might adversely affect childhood neurodevelopment. The gender-specific associations existed in the above associations.

Protocol for Multi-modality MEdical imaging sTudy bAsed on KaiLuan Study (META-KLS): rationale, design and database building.

INTRODUCTION: Multi-modality medical imaging study, especially brain MRI, greatly facilitates the research on subclinical brain disease. However, there is still a lack of such studies with a wider age span of participants. The Multi-modality MEdical imaging sTudy bAsed on KaiLuan Study (META-KLS) was designed to address this issue with a large sample size population. METHODS AND ANALYSIS: We aim to enrol at least 1000 subjects in META-KLS. All the participants without contraindications will perform multi-modality medical imaging, including brain MRI, retinal fundus photograph, fundus optical coherence tomography (OCT) and ultrasonography of the internal carotid artery (ICA) every 2-4 years. The acquired medical imaging will be further processed with a standardised and validated workflow. The clinical data at baseline and follow-up will be collected from the KaiLuan Study. The associations between multiple risk factors and subclinical brain disease are able to be fully investigated. Researches based on META-KLS will provide a series of state-of-the-art evidence for the prevention of neurological diseases and common chronic diseases. ETHICS AND DISSEMINATION: The Kailuan Study and META-KLS have been approved by the Medical Ethics Committee of Kailuan General Hospital (IRB number: 2008 No. 1 and 2021002, respectively). Written informed consent will be acquired from each participant. Results are expected to be published in professional peer-reviewed journals beginning in 2023. TRIAL REGISTRATION NUMBER: NCT05453877.

Prospective associations between various prenatal exposures to maternal psychological stress and neurodevelopment in children within 24 months after birth.

BACKGROUND: There is increasing evidence that prenatal exposure to maternal psychological distress may be a factor influencing offspring neurodevelopment, but stress type-dependent effects of maternal psychological distress on offspring neurodevelopment in early childhood have yet to be fully elucidated. Additionally, although positive maternal mental health exerts potential effects in protecting against adverse health outcomes, few investigators have considered the effects of positive maternal mental health on offspring neurodevelopment in early childhood. AIMS: To determine the associations between various prenatal exposures to maternal psychological distress and positive life-event experiences and offspring neurodevelopment within 24 months of age. METHODS: A total of 4412 mother-child dyads were recruited from the Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC). Maternal perceived stress, negative life-event stress, positive life-event experiences around the time of conception (i.e., three months prior to and after conception) were assessed at 12-16 gestational weeks, and maternal anxiety and depressive symptoms were assessed at 32-36 gestational weeks. We measured children's neurodevelopment using the Ages and Stages Questionnaire, Third Edition (ASQ-3) at two, six, 12, and 24 months postnatally. We then exploited generalized linear models to estimate the associations between prenatal maternal psychological distress and positive life-event experiences and children's neurodevelopment at the above periods, and generalized linear mixed models were applied to assess the associations between maternal psychological distress and positive life-event experiences and suspected developmental delay (SDD) in children within 24 months after birth based on a longitudinal design. RESULTS: Maternal perceived stress and negative life-event stress around the time of conception, and anxiety and depressive symptoms during late pregnancy were negatively associated with scores of children's neurodevelopment at two, six, 12, and 24 months of age; while maternal life-event experiences were positively associated with scores of children's neurodevelopment. Longitudinal analysis revealed that higher levels of maternal negative life-event stress and depressive symptoms augmented the risk of SDD in personal-social (OR = 1.435, 1.681). Mothers who experienced higher levels of positive life-event experiences exhibited a reduced risk of SDD in gross motor and personal-social domains (OR = 0.373, 0.350). CONCLUSIONS: Prenatal exposure to maternal psychological distress is negatively associated with children's neurodevelopment in early childhood depending upon the type of distress. Maternal positive life-event experiences around the time of conception appeared to present potential benefits for child neurodevelopment.

Mixed exposure to phthalates and organic UV filters affects Children's pubertal development in a gender-specific manner.

BACKGROUND: Previous studies showed phthalates and UV filters are endocrine-disruptive and associated with puberty. However, few studies have examined effects of mixed exposure. METHODS: Six phthalate metabolites and 12 organic UV filters were detected among 223 school-age children. Puberty development was evaluated at baseline and after 18 months of follow-up. Ordered logistic regression models, least absolute shrinkage and selection operator (LASSO) regression and quantile-based g-computation (qgcomp) were used to evaluate relationships between phthalate metabolites or UV filters exposure and pubertal development. RESULTS: Six phthalate metabolites and 5 UV filters were detectable in urine samples. In boys, BP-3 and 4'-MAP were negatively associated with genital (ORBP-3 = 0.52, (0.27, 0.93), OR4'-MAP = 0.45, (0.25, 0.74)) and pubic hair development (ORBP-3:0.24, (0.05, 0.76), OR4'-MAP:0.24, (0.05, 0.77)). In girls, MEP levels were associated with advanced breast development (OR: 1.29, (1.04, 1.64)). LASSO regression identified BP-3, 4'-MAP, and OD-PABA for inverse associations with pubertal development in boys. MEP was related to an increase in girls' breast development (OR: 1.64, (1.08, 2.63)). Overall mixture was related to a 70% reduction in boys' genital development stage, with a larger effect size than a single chemical in qgcomp. Mixed exposure was associated with girls' earlier puberty onset (OR: 2.61, (1.06, 6.42)). CONCLUSIONS: Our results suggested higher levels of phthalate metabolites and UV filters were associated with delayed pubertal development in boys but with earlier puberty in girls. Higher effect size of joint exposure than single chemicals suggested phthalates and UV filters might have synergistic effects on puberty and distort adolescent endocrine function together.