Prenatal exposure to concentrated ambient PM2.5 results in spatial memory defects regulated by DNA methylation in male mice offspring.

Ambient fine particulate matter (PM2.5) exposures during pregnancy could lead to adverse birth outcomes, including neurobehavioral development defects. However, limited studies explored the effects and potential epigenetic mechanisms of maternal PM2.5 exposure on offspring spatial memory defects. This study aims to explore the effects and underlying epigenetic mechanisms of maternal concentrated ambient PM2.5 exposure in male mice offspring with spatial memory defects. Pregnant female C57BL/6 mice were exposed daily to concentrated ambient PM2.5 (CAP) or filtered air (FA) throughout gestation, with the concentration of particulates (102.99 ± 78.74 µg/m3) and (2.78 ± 1.19 µg/m3), respectively. Adult male mice offspring were subsequently assessed for spatial learning and memory ability using Morris Water Maze tests and locomotor activities in open field tests. The hippocampus of the male mice offspring was harvested to test mRNA expression and DNA methylation. Results from the probe test of Morris Water Maze showed that the mice offspring in the CAP group had shorter swimming distance travelled in the target quadrant, shorter duration in the target quadrant, and less number of entries into the target quadrant (p < 0.05), suggesting spatial memory impairments. The acquisition trials of Morris Water Maze did not show a significant difference in learning ability between the groups. The mRNA level of interleukin 6 (IL-6) in the CAP group hippocampus (10.80 ± 7.03) increased significantly compared to the FA group (1.08 ± 0.43). Interestingly, the methylation levels of the CpG sites in the IL-6 promoter region declined significantly in the CAP group, (5.66 ± 0.83)% vs. (4.79 ± 0.48)%. Prenatal exposure to concentrated ambient PM2.5 induced long-lasting spatial memory defects in male mice offspring. The underlying biological mechanism might be mediated by an inflammatory reaction which is regulated by DNA methylation.

The association between serum folate and gestational diabetes mellitus: a large retrospective cohort study in Chinese population.

OBJECTIVE: To investigate the association between folate levels and the risk of gestational diabetes mellitus (GDM) risk during the whole pregnancy. DESIGN: In this retrospective cohort study of pregnant women, serum folate levels were measured before 24 gestational weeks (GW). GDM was diagnosed between 24th and 28th GW based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. General linear models were performed to examine the association of serum folate with plasma glucose (i.e. linear regressions) and risk of GDM (i.e. log-binomial regressions) after controlling for confounders. Restricted cubic spline regression was conducted to test the dosage-response relationship between serum folate and the risk of GDM. SETTING: A sigle, urban hospital in Shanghai, China. PARTICIPANTS: A total of 42 478 women who received antenatal care from April 2013 to March 2017 were included. RESULTS: Consistent positive associations were observed between serum folate and plasma glucose levels (fasting, 1-h, 2-h). The adjusted relative risks (RR) and 95 % CI of GDM across serum folate quartiles were 1·00 (reference), 1·15 (95 % CI (1·04, 1·26)), 1·40 (95 % CI (1·27, 1·54)) and 1·54 (95 % CI (1·40, 1·69)), respectively (P-for-trend < 0·001). The positive association between serum folate and GDM remained when stratified by vitamin B12 (adequate v. deficient groups) and the GW of serum folate measurement (≤13 GW v. >13 GWs). CONCLUSIONS: The findings of this study may provide important evidence for the public health and clinical guidelines of pregnancy folate supplementation in terms of GDM prevention.

A facile turn-on chemiluminescence probe for sensitive imaging on aminopeptidase N activity.

Aminopeptidase N, as a target for drug discovery, shows marked relationships with many diseases, especially liver injury and cancer. Here, we explored a chemiluminescence (CL) probe for sensing APN by tethering the APN-specific substrate group to the ortho-acrylated phenoxy-dioxetane scaffold. In this way, two CL probes (APN-CL and BAPN-CL) were designed with noncapped leucine and butoxy-carbonyl capped leucine as the protecting group to preserve the chemiexcitation energy. The uncovered leucine was demonstrated to be essential for detection of APN activity by comparing the CL intensity of two CL probes. Probe APN-CL was turned on upon APN cleavage, resulting in a high chemiluminescent emission, whereas the chemiexcitation energy of probe BAPN-CL was still restrained even with the high-level APN. The result was further elucidated by molecular docking simulations. Probe APN-CL exhibited a fast response and high sensitivity with a detection limit of 0.068 U/L, and an excellent specificity for the discrimination of APN from biological ions, small molecules, and other proteases commonly found in living system. By virtue of good stability and cell viability, probe APN-CL imaged abnormal levels of APN in tumour cells and tumour-bearing mice. Moreover, this probe APN-CL could be easily used to evaluate APN inhibitors and APN levels in plasma samples from 20 patients. Overall, as a facile and cost-effective probe, APN-CL will be a promising alternative in the early diagnosis of pathologies and for cost-effective screening of inhibitors.

Understanding the Joint Impacts of Cognitive, Social, and Geographic Proximities on the Performance of Innovation Collaboration Between Knowledge-Intensive Business Services and the Manufacturing Industry: Empirical Evidence From China.

Most previous empirical studies just addressed the influence of geographical proximity on interactive learning regarding the collaboration between knowledge-intensive business service (KIBS) and manufacturing industries. Drawing upon the social cognitive and knowledge-based perspective, this study bridged the research gaps by investigating the joint effects of geographical proximity and two representative non-geographic-proximities (i.e., cognitive proximity and social proximity) in fostering manufacturing firms' innovation performance. In terms of the empirical analysis, we applied a research sample that involves the data of various manufacturing industries in 260 cities of China from 2003 to 2014 to test the corresponding hypotheses. Additionally, the Spatial Durbin Model (SDM) was adopted and the research findings showed that: (i) the geographic and social proximity significantly promote the knowledge transfer from KIBS to manufacturing firms, which further improves the innovation performance of the latter. However, the effect of cognitive proximity presents insignificant; (ii) the interactive effect of geographic and social proximity was positively associated with the innovation collaboration between KIBS and manufacturing firms; (iii) although the individual effect of cognitive proximity was insignificant, when it interacted with geographic or social proximity, the joint effects were proved to promote the innovation performance of manufacturing firms. This study extends our understanding pertaining to the influencing mechanism of proximity for KIBS and the innovation process. The findings proved that geographic and social proximity are two imperative facilitators of knowledge-creating collaboration, highlighting their indispensable role in moderating and mediating the knowledge transfer of KIBS as well as the innovation performance of manufacturing firms. Notably, cognitive proximity is contingent upon geographic and social proximity on its positive effects on the innovation performance for KIBS and their clients' collaboration.

Magnetic covalent organic framework nanospheres-based miRNA biosensor for sensitive glioma detection.

Sensitive detection and accurate diagnosis/prognosis of glioma remain urgent challenges. Herein, dispersed magnetic covalent organic framework nanospheres (MCOF) with uniformed Fe3O4 nano-assembly as cores and high-crystalline COF as shells were prepared by monomer-mediated in-situ interface growth strategy. Based on the unique interaction between MCOF and hairpin DNA, a fluorescent signal amplified miRNA biosensor was constructed. It could realize the sensitive detection of miRNA-182 in different matrixes, where the detection limit, linearity range and determination coefficient (R2) in real blood samples reached 20 fM, 0.1 pM-10 pM and 0.991, respectively. Also, it possessed good stability and precision as observed from the low intra-day/inter-day RSD and high extraction recovery. As a result, it could quantify miRNA-182 in serum of glioma patients, the concentration of which was significantly higher than that of healthy people and obviously decreased after surgery. Finally, a proof-of-concept capillary chip system using this biosensor was proposed to realize the visualized detection of miRNA-182 in microsample. These findings suggest a robust way for sensitive detection and accurate diagnosis/prognosis of glioma.

Association between the home environment and development among 3- to 11-month infants in Shanghai, China.

BACKGROUND: Literature highlighted the home environment as a major factor influencing the overall development of children. However, minimal information is available about the home environment in China and especially in small infants. This survey was conducted to find out the association between the home environment and the early development of infants. METHODS: A total of 1850 infants aged 3-11 months were randomly selected during December 2014 to September 2015. Affordances in the Home Environment for Motor Development-Infant Scale (AHEMD-IS) was used to measure the home environment considering the availability of toys, physical space and variety of stimulation. The Age and Stage Questionnaire-Chinese (ASQ-C) was used to measure potential developmental delays among infants. Bivariate logistic regression model was used to test the association between home environment and potential developmental delays. RESULTS: The percentages of infants with insufficient activity space ranged from 25.27% to 30.23%. With the increase of age, the number of toys available to infants was also increasing. However, varieties of stimulation were decreasing. Compared with infants who have sufficient physical space, the risk of problem-solving development delay increased 26.0% (OR = 0.74, 95% CI: 0.56, 0.97). The risk of gross motor delay was 47.0% (OR = 0.53, 95% CI: 0.53, 0.99) lower in infants with sufficient variety of stimulation than infants without. Fine-motor toys were associated with all domains in ASQ-C except communication development, while gross motor toys mainly affected fine motor and problem-solving development. CONCLUSION: Positive associations between home environment and development among 3- to 11-month infants in Shanghai, China, were revealed in the current study. The results from the study are expected to be useful for early childhood caretakers, public health practitioners and other professionals to plan interventions, especially for low-income families living in a disadvantaged environment.

Brain-wide neural dynamics of poststroke recovery induced by optogenetic stimulation.

Poststroke optogenetic stimulations can promote functional recovery. However, the circuit mechanisms underlying recovery remain unclear. Elucidating key neural circuits involved in recovery will be invaluable for translating neuromodulation strategies after stroke. Here, we used optogenetic functional magnetic resonance imaging to map brain-wide neural circuit dynamics after stroke in mice treated with and without optogenetic excitatory neuronal stimulations in the ipsilesional primary motor cortex (iM1). We identified key sensorimotor circuits affected by stroke. iM1 stimulation treatment restored activation of the ipsilesional corticothalamic and corticocortical circuits, and the extent of activation was correlated with functional recovery. Furthermore, stimulated mice exhibited higher expression of axonal growth-associated protein 43 in the ipsilesional thalamus and showed increased Synaptophysin+/channelrhodopsin+ presynaptic axonal terminals in the corticothalamic circuit. Selective stimulation of the corticothalamic circuit was sufficient to improve functional recovery. Together, these findings suggest early involvement of corticothalamic circuit as an important mediator of poststroke recovery.

An activatable chemiluminescence probe based on phenoxy-dioxetane scaffold for biothiol imaging in living systems.

Quantification of biothiols in living systems is essential to understand their biological applications. Here, we developed two activatable chemiluminescence probes (SHCL and NCCL) and investigated their utility in the bioimaging of intracellular biothiols by directly tethering 2,4-dinitrobenzenesulfonyl to the hydroxyl group of phenoxy-dioxetane. The design of these two probes differed in substituents of phenol-dioxetane, i.e., SHCL contained the ortho chlorine, whereas NCCL had the para hydroxymethyl. Upon glutathione (GSH) cleavage, both probes emitted significantly "turn-on" chemiluminescent signals. However, the chemiluminescence intensity based on NCCL declined with increasing GSH level above 5 mM, while SHCL exhibited much higher chemiluminescent intensity and a wider concentration range (0.5 µM-50 mM), which was much more suitable for sensing endogenous biothiols. We further demonstrated that chlorine substitution in SHCL played an important role in bioimaging owing to the halogen effect, providing a lower pKa value and significant enhancement of the chemiluminescent emission. SHCL imaged the biothiols effectively in tumor cells and tumor-bearing mice. Additionally, this novel chemiluminescence probe can be easily used to evaluate the in vitro activity of acetylcholinesterase. Overall, we anticipate that SHCL may provide a facile and intuitive tool for studying the role of biothiols in diseases.

A Novel Chemiluminescence Probe for Sensitive Detection of Fibroblast Activation Protein-Alpha In Vitro and in Living Systems.

Fibroblast activation protein-alpha (FAPα) is a key modulator of the microenvironment in multiple pathologies and is becoming the next pan-cancer target for cancer diagnostics and therapeutics. Chemiluminescence (CL) luminophores are considered as one of the most sensitive families of probes for detection and imaging applications due to their high signal-to-noise ratio. Until now, however, no such effective CL probe was reported for FAPα detection. Herein, we developed a novel CL probe for the detection of endogenous FAPα activity by incorporating FAPα-specific dipeptide substrates (glycine-proline) to the improved Schaap's adamantylidene-dioxetane. In this manner, we designed three CL probes (CFCL, BFCL, and QFCL) with the dipeptide substrate blocked by N-terminal benzyloxycarbonyl, N-tert-butoxycarbonyl or N-quinoline-4-carboxylic acid, respectively, which was used as the masking group to restrain the chemiexcitation energy. Probe CFCL exhibited the optimal specificity for the discrimination of FAPα from dipeptidase IV and prolyl oligopeptidase, which was elucidated by molecular docking simulation. Upon FAPα cleavage, CFCL was turned on for the highly selective and sensitive detection of FAPα with a limit of detection of 0.785 ng/mL. Furthermore, the ability of CFCL to image FAPα was effectively demonstrated in vitro, including various biological samples (plasma and tissue preparations), and in living systems (tumor cells and tumor-bearing mice). Furthermore, this newly established probe could be easily extended to evaluate FAPα inhibitors. Overall, we anticipate that probe CFCL will offer a facile and cost-effective alternative in the early detection of pathologies, individual tailoring of drug therapy, and drug screening.

Unique Subtype of Microglia in Degenerative Thalamus After Cortical Stroke.

BACKGROUND AND PURPOSE: Stroke disrupts neuronal functions in both local and remotely connected regions, leading to network-wide deficits that can hinder recovery. The thalamus is particularly affected, with progressive development of neurodegeneration accompanied by inflammatory responses. However, the complexity of the involved inflammatory responses is poorly understood. Herein we investigated the spatiotemporal changes in the secondary degenerative thalamus after cortical stroke, using targeted transcriptome approach in conjunction with histology and flow cytometry. METHODS: Cortical ischemic stroke was generated by permanent occlusion of the left middle cerebral artery in male C57BL6J mice. Neurodegeneration, neuroinflammatory responses, and microglial activation were examined in naive and stroke mice at from poststroke days (PD) 1 to 84, in both ipsilesional somatosensory cortex and ipsilesional thalamus. NanoString neuropathology panel (780 genes) was used to examine transcriptome changes at PD7 and PD28. Fluorescence activated cell sorting was used to collect CD11c+ microglia from ipsilesional thalamus, and gene expressions were validated by quantitative real-time polymerase chain reaction. RESULTS: Neurodegeneration in the thalamus was detected at PD7 and progressively worsened by PD28. This was accompanied by rapid microglial activation detected as early as PD1, which preceded the neurodegenerative changes. Transcriptome analysis showed higher number of differentially expressed genes in ipsilesional thalamus at PD28. Notably, neuroinflammation was the top activated pathway, and microglia was the most enriched cell type. Itgax (CD11c) was the most significantly increased gene, and its expression was highly detected in microglia. Flow-sorted CD11c+ microglia from degenerative thalamus indicated molecular signatures similar to neurodegenerative disease-associated microglia; these included downregulated Tmem119 and CX3CR1 and upregulated ApoE, Axl, LpL, CSF1, and Cst7. CONCLUSIONS: Our findings demonstrate the dynamic changes of microglia after stroke and highlight the importance of investigating stroke network-wide deficits. Importantly, we report the existence of a unique subtype of microglia (CD11c+) with neurodegenerative disease-associated microglia features in the degenerative thalamus after stroke.

Pre-pregnancy exposure to fine particulate matter (PM2.5) increases reactive oxygen species production in oocytes and decrease litter size and weight in mice.

Exposure of females to fine particulate matter ≤2.5 µm in diameter (PM2.5) prior to pregnancy could produce adverse impact on fertility and enhances susceptibility of the offspring to a variety of diseases. In the current study, female C57BL/6 mice (6 weeks of age) were exposed to either concentrated PM2.5 or filtered air (average PM2.5 concentration: 115.60 ± 7.77 vs. 14.07 ± 0.38 µg/m-3) using a whole-body exposure device for 12 weeks. Briefly, PM2.5 exposure decreased anti-Müllerian hormone level (613.40 ± 17.36 vs 759.30 ± 21.90 pg mL-1, P＜0.01) and increased reactive oxygen species (ROS) level (45.39 ± 0.82 vs 24.20 ± 0.85 arbitrary unit in fluorescence assay, P＜0.01) in oocytes. The exposure increased oocyte degeneration rate (21.5% vs 5.1%, respectively (P＜0.01) and decreased the 2-cell formation rate (71.9% vs 86.0%, P < 0.01). Transcriptome profiling using RNA sequencing showed wide spectrum of abnormal expression of genes, particularly those involved in regulating the mitochondrial respiratory complex in oocytes and metabolic processes in blastocysts. The exposure decreased litter size (6 ± 0.37 vs 7 ± 0.26, P＜0.05) and weight (1.18 ± 0.02 vs 1.27 ± 0.02 g, P＜0.01). In summary, PM2.5 exposure decreased female fertility, possibly through increased ROS production in oocytes and metabolic disturbances in developing embryos. The cause-effect relationship, however, requires further investigation.

Prenatal exposure to fine particulate matter and fetal growth: a cohort study from a velocity perspective.

BACKGROUND: Reduced growth velocity before birth increases the risk of adverse health outcomes in adult life. However, until recently, there has been a lack of studies demonstrating the impact of prenatal PM2.5 exposure on fetal growth velocity. METHODS: The current study was embedded in a previous cohort built between January 1, 2014, and April 30, 2015, in Shanghai First Maternity and Infant Hospital, China, in 6129 eligible singleton pregnancies. The PM2.5 concentration was estimated by an inverse distance weighted method according to the residential addresses of the participants. Repeated fetal biometry measurements, including head circumference (HC), abdominal circumference (AC), femur length (FL), and biparietal diameter (BPD), were measured through ultrasound between 14 and 41 gestational weeks. A principal component analysis through conditional expectation for sparse longitudinal data was used to estimate the corresponding velocities. RESULTS: A total of 22782 ultrasound measurements were conducted among 6129 participants with a median of 2 and a maximum of 9 measurements. With each 10 µg/m3 increase in cumulative PM2.5 exposure, the velocity of HC, AC FL and BPD decreased by 0.12 mm/week, 0.17 mm/week, 0.02 mm/week and 0.02 mm/week, respectively, on average. The results of the Generalized Functional Concurrent Model showed that the velocity decreased significantly with PM2.5 exposure between 22 and 32 gestational weeks, which might be the potential sensitive exposure window. CONCLUSIONS: There are negative associations between prenatal exposure to PM2.5 and fetal growth velocity, and the late second trimester and early third trimester might be the potential sensitive window.

Inflammatory Responses in the Secondary Thalamic Injury After Cortical Ischemic Stroke.

Stroke is one of the major causes of chronic disability worldwide and increasing efforts have focused on studying brain repair and recovery after stroke. Following stroke, the primary injury site can disrupt functional connections in nearby and remotely connected brain regions, resulting in the development of secondary injuries that may impede long-term functional recovery. In particular, secondary degenerative injury occurs in the connected ipsilesional thalamus following a cortical stroke. Although secondary thalamic injury was first described decades ago, the underlying mechanisms still remain unclear. We performed a systematic literature review using the NCBI PubMed database for studies that focused on the secondary thalamic degeneration after cortical ischemic stroke. In this review, we discussed emerging studies that characterized the pathological changes in the secondary degenerative thalamus after stroke; these included excitotoxicity, apoptosis, amyloid beta protein accumulation, blood-brain-barrier breakdown, and inflammatory responses. In particular, we highlighted key findings of the dynamic inflammatory responses in the secondary thalamic injury and discussed the involvement of several cell types in this process. We also discussed studies that investigated the effects of blocking secondary thalamic injury on inflammatory responses and stroke outcome. Targeting secondary injuries after stroke may alleviate network-wide deficits, and ultimately promote stroke recovery.

Concentrated ambient PM2.5 exposure affects mice sperm quality and testosterone biosynthesis.

BACKGROUND: Studies suggested that PM2.5 exposure could lead to adverse reproductive effects on male animals. However, the underlying mechanism is still not clear. Besides, animals in the majority of previous studies were exposed to PM2.5 through intratracheal instillation which should be improved. In addition, limited amount of research has been conducted in China where the PM2.5 concentration is higher and the PM2.5 components are different. The aim of this work is to explore the effects of concentrated ambient PM2.5 (CAP) on mice sperm quality and testosterone biosynthesis. METHODS: A total of 12 male C57BL/6 mice were exposed to filtered air (FA) or CAP for 125 days using the Shanghai Meteorological and Environmental Animal Exposure System. The mice sperm concentration, sperm motility, DNA fragmentation index, high DNA stainability and plasma testosterone were analyzed. Testicular histology and sperm morphology were observed through optical microscope. Testosterone biosynthesis related gene expressions were analyzed using real-time PCR, including cytochrome P450 CHOL side-chain cleavage enzyme (P450scc), steroidogenic acute regulatory protein (StAR), 3ß-hydroxysteroid dehydrogenase (3ß HSD), 17ß-hydroxysteroid dehydrogenase, cytochrome P450 aromatase (P450arom), estrogen receptor (ER), androgen receptor (AR) and follicle stimulating hormone receptor (FSHR). RESULTS: Exposure to CAP resulted in disturbance of various stages of spermatogenesis and significant higher percentage of abnormal sperm (FA vs. CAP: 24.37% vs. 44.83%) in mice testis. CAP exposure significantly decreased sperm concentration (43.00 × 106 vs. 25.33 × 106) and motility (PR: 63.58% vs. 55.15%; PR + NP: 84.00% vs. 77.08%) in epididymis. Plasma testosterone concentration were significantly declined (0.28 ng/ml vs. 0.69 ng/ml) under CAP exposure. Notably, the levels of testosterone biosynthesis related genes, StAR, P450scc, P450arom, ER and FSHR were significantly decreased with CAP exposure. CONCLUSION: Concentrated ambient PM2.5 exposure altered mice sperm concentration, motility and morphology, which might be mediated primarily by the decline in testosterone concentration and testosterone biosynthesis process.

Ultrasensitive Chemiluminescence Biosensor for Nuclease and Bacterial Determination Based on Hemin-Encapsulated Mesoporous Silica Nanoparticles.

Bacterial determination, emerging as a critical step in the understanding of increasingly serious bacterial contaminations, remains a major challenge. Herein, a novel chemiluminescence biosensor was exploited for the ultrasensitive determination of nuclease activity and bacteria, in which, hemin, the chemiluminescent (CL) tag molecule was encapsulated into ordered mesopores of mesoporous silica nanoparticles with a specific DNA gate. The capped DNA could be specifically switched upon exposure to the DNA nuclease or bacterial lysate and allowed for an increased release of the encapsulated hemin, which therefore resulted in an obviously enhanced CL signal for the luminol-H2O2 system. Attributed to this unique behavior with the linear or sigmoidal relationship between CL intensity and DNA nuclease or bacterial concentration, the as-prepared CL biosensor could detect S1 nuclease activity in the concentration range 0.01-10.0 U with a detection limit of 0.1 mU, and Escherichia coli O157:H7 (E. coli) or Staphylococcus aureus (S. aureus) in the concentration ranges 101 to 109 cfu mL-1. The detection limit of E. coli and S. aureus was calculated to be 3.0 and 2.5 cfu mL-1, respectively, which was comparable or even better than that of previous studies. Thus, this detection method could achieve detectable levels without cell enrichment overnight. Moreover, the proposed biosensing system could be conducted in the homogeneous solution without separation and washing, greatly improving the reaction efficiency and simplifying the procedure. As expected, the novel CL biosensor promised a great potential for simple and convenient detection of nuclease and bacteria in fields such as food bacterial contamination, pharmaceuticals, and clinical analysis.

Maternal exposure to ambient fine particulate matter and fetal growth in Shanghai, China.

BACKGROUND: Fetal growth restriction (FGR) is not only a major determinant of perinatal morbidity and mortality but also leads to adverse health effects in later life. Over the past decade, numerous studies have indicated that maternal exposure to ambient air pollution has been a risk factor for abnormal fetal growth in developed countries where PM2.5 levels are relatively low. However, studies in highly polluted regions, such as China, and studies that rely on assessments in utero are scarce. METHODS: A total of 7965 women were selected from 11,441 women from the Shanghai Maternity and Infant Living Environment (SMILE) cohort who were pregnant between January 1, 2014, and April 30, 2015. From January 1, 2014, to April 30, 2015, weekly average PM2.5 values from 53 monitors were calculated and the inverse distance weighted (IDW) method was used to create a Shanghai pollution surface map according to the participants residential addresses. Individual exposure was the average PM2.5 value of every gestational week between the first gestational week and one week before the ultrasound measurement date (the range of measurements per participant was 1 to 10). Repeated fetal ultrasound measurements during gestational weeks 14~40 were selected. The estimated fetal weight (EFW) was calculated by biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL) formulas. In total, 29,926 ultrasound measurements were analysed. Demographic variables, other pollutants (SO2, NO2, PM10 and O3) and relative humidity and temperature were controlled for potential confounding through generalized estimating equations (GEE). RESULTS: The full model showed that with each 10 µg/m3 increase in PM2.5 exposure, the means (mm) of AC, BPD, FL decreased by 5.48 (- 9.06, - 1.91), 5.57 (- 6.66, - 4.47), and 5.47 (- 6.39, - 4.55), respectively; the mean EFW decreased by 14.49 (- 16.05, - 13.49) grams by Hadlock's third formula and 13.56 (- 14.71, - 12.50) grams by Shepard's formula with each 10 µg/m3 increase in PM2.5 exposure. CONCLUSIONS: A negative correlation existed between maternal PM2.5 exposure during pregnancy and fetal growth indicators, which may increase the risk of fetal growth restriction.

Differentiating the cognitive development of early-term births in infants and toddlers: a cross-sectional study in China.

OBJECTIVES: This study aimed to explore the cognitive development of low-risk children during early childhood for early-term births at 37 and 38 weeks of gestation compared with full term births at 39-41 weeks of gestation. SETTING AND PARTICIPANTS: We conducted a cross-sectional study in Shanghai, one of the largest cities in China. A total of 1444 children from singleton pregnancies born at term gestation were included in the study. MEASURES: The cognitive outcomes of the subjects were measured using the cognitive subtest of Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) across three cities in China. We analysed the association between gestational age and cognitive development during infancy and toddler stages using multivariate linear modelling. RESULTS: The cognitive development scores for infants born at 37 gestational weeks were significantly lower than those born at 39-41 gestational weeks (ß=-2.257, 95% CI -4.280 to -0.235; p<0.05) after adjusting for children's and maternal characteristics, as well as socio-economic factors. However, there were no significant differences in cognitive ability between infants born at 38 gestational weeks compared with their full-term counterparts (p>0.05). Moreover, these effects were not found in toddlers (between 17 and 48 months of age) after adjusting for the possible confounders (p>0.05). CONCLUSIONS: Infants born at 37 weeks of gestation exhibited weaker cognitive ability compared with those born at 39-41 weeks of gestation. Our findings provide evidences for the close monitoring of potential developmental problems in early-term children, especially those born at 37 gestational weeks.

Association between isolated hypothyroxinaemia in early pregnancy and perinatal outcomes.

BACKGROUND: The effect of isolated maternal hypothyroxinaemia (IMH) on pregnancy complications and neonatal outcomes in human beings is still controversial. METHODS: This was a retrospective cohort study based on the electronic medical register system. The records of women with a singleton pregnancy who sought antenatal examination between January 2014 and December 2015 at Shanghai First Maternity and Infant Hospital were extracted from the electronic medical records system. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and anti-thyroperoxidase autoantibody (TPO-Ab) was measured before 20 gestational weeks, and a multiple logistic regression model was used to estimate the odds ratios of pregnancy complications and neonatal outcomes between euthyroid women and those with isolated hypothyroxinaemia. RESULTS: A total of 8173 women were included in this study, of whom 342 (4.18%) were diagnosed with IMH. Regression analysis showed that IMH diagnosed in the second trimester (13-20 weeks) was associated with an increased risk of hypertensive disorders of pregnancy (OR = 2.66, 95% CI: 1.38-5.10) and placenta abruption (OR = 3.64, 95% CI: 1.07-12.41), but not with preterm delivery (OR = 1.09, 95% CI: 0.50-2.40), small or large gestational age of infant (OR = 0.91, 95% CI: 0.39-2.12; OR = 1.16, 95% CI: 0.72-1.86), macrosomia (OR = 1.71, 95% CI: 0.95-3.07), gestational diabetes mellitus (OR = 1.36, 95% CI: 0.86-2.15) and placenta previa (OR = 1.62, 95% CI: 0.39-7.37). CONCLUSION: IMH could be a risk factor for hypertensive disorders of pregnancy.