BACKGROUND:Evidence on exposure to metal-vitamin mixtures in relation to hypertensive disorders of pregnancy (HDP) remains limited. We examined the associations of first-trimester exposure to these mixtures with HDP risk, with stratification by BMI for effect modification analyses. METHODS:We conducted a nested case-control study within a prospective cohort of 2069 pregnant women. First-trimester plasma concentrations of ten metallic elements (manganese, chromium, cobalt, selenium, arsenic, cadmium, lead, thallium, vanadium, nickel) and two vitamins (vitamins B12 and folate) were measured. After exclusions, 134 HDP cases were matched to 399 controls (1:3 ratio) by maternal age and infant sex. Associations with HDP risk and blood pressure were assessed using conditional logistic regression and linear mixed models with stratification by BMI. Quantile-based g-computation, Bayesian kernel machine regression, and restricted cubic splines were employed to examine mixture effects and non-linear relationships. RESULTS:Nickel was consistently associated with increased HDP risk (OR: 1.240, 95% CI: 1.118-1.375) and higher perinatal systolic blood pressure (β: 0.589, 95% CI: 0.145-1.032), while vitamin B12 showed protective effects (OR: 0.998, 95% CI: 0.996-1.000) (β: -0.009, 95% CI: -0.017--0.001). Manganese demonstrated a U-shaped relationship with HDP, with the lowest risk at plasma concentrations of 1.44-4.80 μg/L. Mixture analyses identified nickel and chromium as key drivers with opposing effects. BKMR revealed a significant pairwise interaction among manganese, chromium, nickel, and vitamin B12. Associations of nickel and vitamin B12 with HDP were significant only in normal-weight women. CONCLUSION:First-trimester metal-vitamin mixtures influence HDP risk through concentration-dependent effects of nickel (adverse), chromium and vitamin B12 (protective), and manganese (U-shaped), with modulation by nutrient-metal interactions and maternal pre-pregnancy BMI.

While the associations among particulate matters (PMs) exposure and neonatal hyperbilirubinemia (NHB) have been studied, the potential protective effect role of perinatal sunlight exposure and its interaction with PMs on NHB remains unclear. Thus, we designed this study to investigate the impact of maternal PMs exposure and sunlight duration on NHB. We included 155,970 pregnant women and their singleton newborns (without ABO hemolytic disease) from two major obstetric hospitals in Shanghai. Generalized linear models were used to evaluate the effects of PM2.5, PM10, and PM2.5-10, daily sunlight duration, and their interactive effects on NHB during different periods throughout the pregnancy. Our findings reveal that the risk of NHB was associated with increased exposure levels of PM2.5-10 (aOR: 1.081; 95%CI: 1.022, 1.144) and PM10 (aOR: 1.046; 95%CI: 1.018, 1.074) and decreased sunlight duration (aOR: 0.900; 95%CI: 0.870, 0.932) during the 3(rd) trimester. While NHB was not directly linked to PM2.5 exposure alone (aOR: 1.025, 95%CI: 0.988, 1.063), we identified a significant interaction between reduced sunlight duration and increased PM2.5 exposure during the 3(rd) trimester (P (for interaction)<0.001), as well as with PM2.5-10 (P (for interaction)=0.030) and PM10 (P (for interaction)=0.032). In conclusion, increased PM2.5-10 and PM10 exposure and decreased sunlight duration during late pregnancy were associated with NHB. Moreover, reduced sunlight duration had an interactive effect with increased concentrations of PM2.5, PM10, and PM2.5-10 on the incidence of NHB. Therefore, mitigating PMs exposure and ensuring adequate sunlight during pregnancy may help reduce the incidence of NHB.

The comprehensive spatiotemporal atlas of gene expression during early human embryonic development is critical for insights into embryogenesis1, organogenesis2 and disease origins3,4. Here, leveraging Stereo-seq technology, we generated spatial transcriptomic profiles across 77 sagittal sections of 13 whole-human embryos ranging from Carnegie stage 12 to 23, integrated with single-nucleus RNA sequencing to elucidate gene expression patterns within defined cellular contexts, revealing the cellular heterogeneity that drives organ-specific differentiation. Our study has established a regulatory profile for the development of 50 organs and 198 substructures, and identified potential tissue-identity regulators. Of note, it uncovered previously uncharacterized gene functions in cardiac and brain development. The atlas not only substantiates and refines the current understanding of human organ development but also highlights key organs susceptible to genetic disorders. Furthermore, we characterized the allelic gene expression within specific organs at different developmental stages. This work presents a comprehensive compilation of genome-wide gene expression profiles for each spatially defined cell population, which can be visualized as a spatial display of the embryonic transcriptional landscape. These results offer the most thorough delineation to data of the spatiotemporal transcriptomic dynamics of human organogenesis.

Maternal prenatal stress confers elevated neuropsychiatric risk to offspring, yet the mechanisms underlying fetal neurodevelopmental impairment remain elusive. The gut microbiota has emerged as a key regulator of brain development and behavior. However, the mechanisms mediating the interactions between the microbiota and the developing brain are still poorly understood. Here, utilizing a prenatal stress mouse model integrated with multi-omics approaches, comprehensive behavioral assays, and molecular validations, we demonstrate that prenatal stress not only induces maternal gut microbiota dysbiosis during pregnancy but also, more critically, leads to fetal blood‒brain barrier (BBB) developmental defects and subsequent abnormalities in emotional behavior and cognitive function in adult offspring. Maternal probiotic supplementation during gestation can reverse both gut microbial dysbiosis and fetal BBB dysfunction. Notably, transcriptomic analysis reveals that the maternal gut microbiota modulates interferon-β (IFN-β) signaling along the placenta‒fetal brain axis under stress. Furthermore, metabolomic profiling suggests that prenatal stress exposure profoundly influences the maternal fecal and serum metabolome. In conclusion, our findings establish a placenta‒brain axis wherein maternal microbial signals orchestrate fetal neurovascular development, identifying microbiota-targeted interventions as a neuroprotective strategy.

Parabens (PBs) are associated with altered fetal growth parameters, but the underlying mechanisms-particularly those involving placental function-remain unclear. To elucidate the mechanisms through PB exposure impairs placental steroidogenic function, thereby contributing to the pathogenesis of fetal growth restriction (FGR). Metabolic profiles in maternal serum samples from FGR cases (n = 20) and the matched controls (n = 20) within a Maternal-Child Health Cohort (Obstetrics & Gynecology Hospital of Fudan University), which were prospectively collected in the first-trimester, were analyzed using UPLC-MS/MS. Trophoblast-derived JEG-3 cells were exposed to butylparaben (BuPB; 1-100 μM, 6-24 h) to assess steroidogenic pathway disruption. Pregnant C57BL/6 mice received subcutaneous BuPB (0, 100 and 400 mg/kg/day, GD 0-13.5) for longitudinal evaluation of exposure effects on placental and fetal development. Pregnancies complicated by FGR exhibited elevated PBs burdens in first-trimester, along with steroidogenic metabolomes significantly disrupted. In vitro exposure of JEG-3 cells to BuPB further confirmed that the estrogen biosynthesis pathway was preferential impaired, as demonstrated by dose-dependent upregulation of HSD3B1 and HSD17B1 expression (1.40-1.42-fold; p < 0.05), while suppression of CYP19A1 expression (35 %-68 % reduction; p < 0.01). In vivo, gestational BuP exposure (GD 0.5-G13.5) induced FGR phenotypes in mice, characterized by reduced fetal weight (28 % decrease; p < 0.01), placental damage. At GD13.5, placental Hsd17b1 was upregulated, while Cyp19a1 was suppressed (p < 0.05) with concomitant estrogen deficiency. Our findings indicate that early gestational BuPB exposure may disrupt placental steroidogenesis, specifically through placental steroidogenesis homeostasis, resulting in placental estrogen deficiency and impaired placenta and fetal development. Our study provided integrated evidences of developmental toxicity of PBs in the pathogenesis of FGR.

Introns have expanded dramatically during evolution, and while their internal sequences have greatly diverged, the potential function of ultraconserved RNA motifs remains an important, unanswered question. Sharing the sequence with the utilized 5' splice sites (5'SSs), pseudo-5'SSs are widespread in introns but are never spliced. We searched homologous introns and identified eight ultraconserved pseudo-5'SSs (UCP-5'SSs). The most conserved one resides in the animal ENOX1/Enox genes that are involved in plasma membrane electron transport and cell enlargement. In vivo deletion of this 9-nt UCP-5'SS in Drosophila results in a significantly enlarged ovary and increased fecundity. We demonstrate that this UCP-5'SS is a silencer for alternative splicing (AS) regulation of an upstream ultraconserved essential exon through interaction with the U1 snRNP-core proteins. The AS changes are observed in all the tested Drosophila mutants from the dTOR and Insulin-like pathways. Remarkably, loss of this UCP-5'SS significantly mitigates the changes. Multiple-source human cells treated with the mTOR/Insulin pathway inhibitors also change the AS and specifically increase the translation of U1-70K, suggesting remarkable conservation of this mechanism. This study reveals an ultraconserved regulatory network in which a short intronic RNA element functions as a sensor of TOR-related pathways during ovarian development.

The effects of maternal antenatal depression (AND) across different stages of pregnancy on offspring neurodevelopment remain poorly understood, and the underlying microbiota-related mechanisms are largely unknown. In a multicenter prospective cohort of 2053 pregnant women, we found that elevated depressive symptoms at any trimester were significantly associated with delayed infant neurodevelopment. Using a nested case‒control design with 16S rRNA sequencing of 504 maternal fecal samples, we identified a consistent reduction of butyrate-producing bacteria and disruption of amino acid metabolism in women with AND symptoms - features that correlated with poorer infant cognitive outcomes. To establish causality, fecal microbiota transplantation (FMT) from women with AND symptoms was administered to germ-free dams, resulting in impaired intestinal barrier integrity, heightened neuroinflammatory signaling, and altered polyunsaturated fatty acid and amino acid metabolism in fetal brains at E18.5, leading to postnatal cognitive deficits in the offspring. Remarkably, maternal butyrate supplementation partially rescued these molecular and neurodevelopmental abnormalities. Together, these findings reveal a mechanistic link between maternal mood, gut microbial ecology, and fetal brain development, and identify the maternal gut microbiota and its metabolites as potential therapeutic targets to prevent the intergenerational effects of antenatal depression.

Emerging evidence shows that the lncRNA THOR is deeply involved in the development of various cancers. However, the effects and underlying molecular mechanisms of THOR in breast cancer (BRCA) initiation and progression have not been fully elucidated. Here we show that THOR is critical for BRCA tumorigenesis by interacting with hnRNPD to regulate downstream signaling pathways. THOR expression was significantly higher in BRCA tissues than in normal tissues, and THOR upregulation was associated with a poor prognosis in BRCA patients. Functionally, THOR knockdown impaired cell proliferation, migration and invasion in BRCA cells in vitro and inhibited tumorigenesis and metastasis in a tumor xenograft model and THOR-deficient MMTV-PyMT model in vivo. Mechanistically, THOR bound to the hnRNPD protein and increased hnRNPD protein levels by maintaining hnRNPD protein stability through inhibition of the proteasome-dependent degradation pathway. The increased hnRNPD protein levels led to stabilization of its target mRNAs, including pyruvate dehydrogenase kinase 1 (PDK1), further activating downstream PI3K–AKT and MAPK signaling pathways to regulate BRCA cell proliferation and metastasis. Together, our findings indicate that THOR is a promising prognostic predictor for BRCA patients and that the THOR–hnRNPD–PDK1–MAPK/PI3K–AKT axis might be a potential therapeutic target for BRCA treatment.

Gestational diabetes mellitus (GDM) remains a prevalent and heterogeneous pregnancy complication with limited strategies for early identification. We aimed to investigate efficient approaches for early prediction of GDM with clinical and genetic risk factors. A previously developed machine-learning model based on clinical characteristics achieved an area under the curve (AUC) of 0.77. To improve predictive accuracy, we further collected non-invasive prenatal testing (NIPT) results from 595 pregnant women (295 with GDM, 300 without). A cumulative polygenic risk score (PRS) was calculated using 1,170 selected single nucleotide variants (SNVs). Logistic regression, support vector machines, random forest, decision tree, linear model and naïve Bayes machine learning models were employed. External validation was performed with an additional 2,350 blood samples independently collected from two other centers. Logistic regression analysis showed that the PRS alone achieved an AUC of 0.75 for GDM discrimination. From cell-free DNA (cfDNA) sequencing performed during NIPT, we identified 357 gene transcripts with differential coverage at transcription start sites. A cfDNA-based linear model achieved an AUC of 0.83 using a subset of 166 signature genes, which reached 0.85 when combined with clinical features. Integration of clinical features, cfDNA, and SNVs yielded the highest performance using a random forest model (AUC = 0.89, specificity = 0.74, sensitivity = 0.89). For external validation, a clinically practical model incorporating clinical features and cfDNA achieved an AUC of 0.83 using linear approach. Our GDM prediction model has reached high accuracy fully using accessible clinical and genetic data routinely generated from current antenatal testing, enabling early screening and interventions for women at risk.

Approximately one-quarter of infants worldwide are born either preterm, with a low birth weight, or both. Maternal anemia significantly increases the risk of adverse birth outcomes. We aimed to investigate the association between hemoglobin levels—alone and in conjunction with chorioamnionitis—and birth outcomes. This retrospective cohort study included 54,300 pregnant women who delivered between January 2018 and December 2023 and whose antenatal examination records were available at a university-affiliated hospital in Shanghai, China. The primary outcomes were preterm birth and low birth weight. In our cohort, 33.9

Maternal exposure to ambient air pollution has been linked to birth defects. However, the relationship between maternal exposure to each air pollutant and live birth defects exhibits significant heterogeneity across different regions and exposure time windows. Here, this study enrolled 190,372 pregnant women who delivered between 2015 and 2020 from two Shanghai hospitals and examined the effects of exposure to 6 types of ambient air pollutants, including particulate matter with a diameter of 2.5 mu m or less (PM2.5), particulate matter with a diameter of 10 mu m or less (PM10), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2) and ozone (O3), on the prevalence of different kinds of live birth defects throughout 3 periods: 3 months before conception, the 1st and 2nd trimester systematically. Significant associations were all confined to the preconception 3-month window. An IQR increase in PM2.5 exposure was linked to any live birth defect, including cardiovascular, orofacial, urogenital, musculoskeletal and others abnormalities. PM10 was associated with orofacial and other abnormalities. No associations were found for SO2, CO, NO2, or O3 in any window. Though the 1sttrimester was not found to be the sensitive window, week-specific effects curves indicated that any live birth defect was found to be associated with exposure to PM2.5 and PM10 during significant vulnerable window, specifically around 0-8 weeks of gestation. Furthermore, sex-stratified results showed maternal PM2.5 exposure linked to any defect in males and PM10 exposure linked to orofacial defects in females during preconception period. In summary, maternal PM2.5 and PM10 exposure during the 3 months before conception increases the risk of live birth defects, with sex-specific susceptibility, highlighting this window for targeted air-quality interventions.

While heavy metals are established contributors to adverse health outcomes, evidence regarding trace element effects on maternal thyroid hormones and birth outcomes remains limited. This prospective study investigated effects of first-trimester exposure to seven trace elements, including vanadium(V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), arsenic (As), and Se (selenium), on maternal third-trimester thyroid hormone levels and birth outcomes in Shanghai, China. Among 2069 enrolled pregnant women, 1351 with complete data were analyzed. Linear regression model, restricted cubic spline (RCS), and quantile g computation (QGC) were employed to assess element-outcome relationships. QGC analysis revealed that the increase in the element’s mixture was associated with the elevation of total triiodothyronine (TT3) (β = 0.026, 95

RESEARCH QUESTION:Can algorithms for prediction of the fertile window and menstruation be developed through machine learning based on women's physiological parameters collected using a wearable device (Huawei Band 6 Pro) from both regular and irregular menstruators? DESIGN:This prospective observational cohort study was conducted at the Obstetrics and Gynaecology Hospital of Fudan University (China). Participants were recruited from November 2021 to September 2022. Each participant used a wearable device to record their wrist skin temperature (WST), heart rate, heart rate variability and respiratory rate for two menstrual cycles. Algorithms were developed to predict the fertile window and menstruation based on WST and heart rate data. RESULTS:Data from 270 and 84 qualifying cycles with confirmed ovulations from 136 regular menstruators and 47 irregular menstruators were included in this study. For regular menstruators, the prediction algorithm based on WST and heart rate data for the fertile window had accuracy of 85.47%, sensitivity of 70.07%, specificity of 89.77%, and area under the curve (AUC) of 0.869. The algorithms for labelling the first day of the menstrual cycle and menstrual prediction 3 days in advance had accuracy of 83.6% and 75.0%, respectively. For irregular menstruators, accuracy, sensitivity, specificity and AUC were 79.85%, 42.79%, 87.28% and 0.763, respectively, for prediction of the fertile window. The accuracy of algorithms for labelling the first day of the menstrual cycle and menstrual prediction were 61.2% and 50.8%, respectively. CONCLUSIONS:Based on WST and heart rate data from the wearable device, the algorithms demonstrated reliable performance in predicting the fertile window and menstruation among regular menstruators. These algorithms also showed potential for assisting irregular menstruators in managing their cycles and planning for conception.

Few studies have reported an association between intrahepatic cholestasis of pregnancy (ICP) and preconception exposure to PM2.5 and sunlight duration, but there has been no in-depth analysis of the correlation between ICP and different constituents of PM2.5. Thus, we performed this retrospective analysis among 160,544 pregnant women who delivered between 2014 and 2020, to further estimate the impact of different constituents of PM2.5, as well as the duration of sunlight, on ICP via generalized linear models. During the three months prior to conception, the adjusted odds ratios (aORs) for ICP were 1.176 (95 % CI: 1.066, 1.298) for a 10 μg/m3 increase in PM2.5, 1.080 (95 % CI: 1.026, 1.138) for a 1 μg/m3 increase in sulfate (SO42-), 1.069 (95 % CI: 1.025, 1.115) for a 1 μg/m3 increase in organic matter (OM), 1.274 (95 % CI: 1.049, 1.546) for a 1 μg/m3 increase in black carbon (BC), and 1.213 (95 % CI: 1.088, 1.353) for a 1-hour decrease in sunlight duration. In addition, during the preconception period, increased exposure to PM2.5 constituents (including SO42-, OM, and BC) and decreased sunlight duration interactively associated with ICP. Moreover, exposure to OM during the first trimester (aOR=1.043, 95 % CI: 1.004, 1.083) and to BC during both the first trimester (aOR=1.201, 95 % CI: 1.000, 1.442) and the second trimester (aOR=1.278, 95 % CI: 1.048, 1.558) were found to elevate the risk of ICP. In the future, women preparing to conceive should increase sunlight exposure and avoid exposure to air pollution, and the constituents related to anthropogenic emissions should be controlled to prevent these associations.

Objective::Frozen-thawed embryo transfer (FET) is widely used in in vitro fertilization (IVF) clinics but is associated with an increased risk of several pregnancy complications, including large-for-gestational age and placenta-related diseases. However, the effects of FET on placentation remain unclear. Therefore, we used single-cell RNA-sequencing (scRNA-seq) technology to investigate the impact of FET on placental gene expression in different subtypes of trophoblasts. Methods::A mouse model of IVF and FET was constructed to collect placenta tissues. scRNA-seq was performed on placentas from two dams undergoing IVF-embryo transfer and two dams undergoing IVF-FET. Differentially expressed gene (DEG) analyses were performed in different subtypes of trophoblasts. Identified DEGs were polymerase chain reaction (PCR) validated.Results::The fetal weights and placental efficiency were higher in the FET group than those in the IVF group at E18.5, with no significant difference in placental weights. Subsequently, 55,406 placental cells were captured and annotated. Upregulated DEGs in the FET group in syncytiotrophoblasts (SynTs) and sinusoidal trophoblast giant cells (S-TGCs) within the placental labyrinth were enriched in pathways related to vascular development and oxidative stress, respectively. The expression of the imprinted gene Igf2 in SynTs, S-TGCs, and spongiotrophoblasts was significantly increased. In the junctional zone, FET upregulated the expression of prolactin genes such as Prl3b1 in glycogen trophoblasts (GlyTs) while the downregulated expression of GlyT genes following FET was associated with mesenchyme development. Conclusions::This study first identifies DEGs and enriched pathways in different subtypes of trophoblasts following FET. These genes and pathways may contribute to the increased placental efficiency and fetal weights. Future studies are required to confirm these results and further explore the key mechanisms in placental pathologies.

BACKGROUND:Women are particularly vulnerable to depression during pregnancy, which is one of the strongest risk factors for developing postpartum depression (PPD). Addressing antenatal depressive symptoms in these women is crucial for preventing PPD. However, little is known about the effectiveness of internet-based cognitive behavioral therapy (ICBT) in preventing PPD in this high-risk group. OBJECTIVE:This study aims to evaluate the short- and long-term effects of ICBT in preventing PPD among women with antenatal depressive symptoms. METHODS:Participants were screened for antenatal depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) and randomly allocated (1:1) to either the ICBT group (receiving weekly online modules starting antenatally and continuing into early postpartum) or the control group (observed without treatment). Follow-up assessments were conducted up to 12 months postpartum, and data were analyzed using generalized estimating equations. The primary outcome was the prevalence of depressive symptoms at 6 weeks postpartum. A subgroup analysis based on the severity of antenatal depressive symptoms was also performed. The secondary outcomes included the long-term effects of ICBT on maternal depression, as well as its impact on anxiety, sleep quality, social support, parenting stress, co-parenting relationships, and infant development. RESULTS:Between August 2020 and September 2021, 300 pregnant individuals were recruited from 5 centers across China. No significant differences were observed in depressive symptoms at 6 weeks postpartum (P=.18) or at any longer-term follow-up time points (P=.18). However, a post hoc subgroup analysis showed that participants with antenatal EPDS scores of 10-12 in the ICBT group had a lower risk of developing depression during the first year postpartum (odds ratio 0.534, 95% CI 0.313-0.912; P=.02), but this was not observed for participants with more severe depression. Additionally, this subgroup demonstrated higher levels of co-parenting relationships (P=.02). CONCLUSIONS:Among individuals with antenatal depression, ICBT did not prevent the development of PPD. However, ICBT may be a preferable option for those with mild to moderate antenatal depressive symptoms. Future research is needed to explore modifications to ICBT to address more severe depressive symptoms. TRIAL REGISTRATION:Chinese Clinical Trial Registry ChiCTR2000033433; https://www.chictr.org.cn/showproj.html?proj=54482. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):RR2-10.1186/s13063-022-06728-5.

Background While maternal psychological stress during mid-to-late pregnancy has been linked to offspring allergies,the impact of early pregnancy distress remains unclear.This study investigates the association between maternal depressive and anxiety symptoms in early pregnancy and allergic diseases in offspring. Methods Based on a birth cohort of 5263 children,antenatal depressive and anxiety symptoms in early pregnancy were assessed via the Patient Health Questionnaire and Generalized Anxiety Disorder Questionnaire,respectively.Allergic out-comes,including asthma,atopic dermatitis(AD),and allergic rhinitis(AR),were evaluated via structured questionnaires.Relative risks(RRs)with 95％confidence intervals(CIs)were estimated via generalized linear models,whereas restricted cubic splines were used to explore linear and non-linear associations between maternal distress and allergic outcomes. Results Maternal depressive symptoms in early pregnancy were associated with an increased risk of AD[adjusted RR(95％CI)=1.15(1.03-1.29)]and AR[1.52(1.29-1.79)].Maternal anxiety symptoms in early pregnancy were associ-ated with increased risks of AD[1.11(1.02-1.21),mild anxiety]and AR[1.33(1.04-1.68),moderate to severe anxiety].Dose-response analyses revealed graded relationships between distress severity and allergic outcomes.In the joint analysis,comorbid depression and anxiety in early pregnancy were associated with an increased risk of AD[1.15(1.05-1.26)]and AR[1.42(1.23-1.63)].Subgroup analysis revealed a greater risk of asthma for boys born to mothers with mild anxiety[1.95(1.20-3.15)]but not for girls. Conclusion Maternal distress in early pregnancy is associated with an increased risk of allergic diseases in offspring during toddlerhood.

BACKGROUND:Gestational diabetes mellitus (GDM) affects millions of females and their children. Effective dietary strategies for early prevention are controversial. OBJECTIVES:This study aims to investigate whether an individualized nutritional intervention reduced GDM incidence in high-risk females. METHODS:A randomized trial was conducted at 3 tertiary hospitals in Shanghai, China. We randomly assigned (1:1) pregnant females in the first trimester who were identified to be at high risk of GDM by a prediction model to either an individualized nutritional intervention or usual care. The intervention consisted of 3 dietary consultations by dietitians based on Chinese dietary guidelines before the oral glucose tolerance test (OGTT) at 24-28 wk of gestation. The control group received usual care. All participants provided 3-d food records at each follow-up. The primary outcome was GDM incidence using the International Association of Diabetes and Pregnancy Study Group criteria. Key secondary outcomes were dietary alterations, gestational weight gain (GWG), maternal metabolic profile, perinatal and pregnancy outcomes. Intention-to-treat analyses were conducted. RESULTS:A total of 519 females were enrolled, of whom 261 were assigned to the intervention and 258 to usual care. GDM was diagnosed in 85/245 (34.7%) females in the intervention group compared with 89/244 (36.5%) in the control group [adjusted relative risk 0.91 (95% confidence interval: 0.73, 1.15), P = 0.44]. More females in the intervention group had an appropriate GWG than the control group [1.38 (1.06, 1.79)] and lower levels of fasting and 2-h insulin during the OGTT (P < 0.001). We observed a reduction in the rate of small for gestational age in the intervention group compared with the control group [0.11 (0.01, 0.80)] and neonatal hypoglycemia [0.14 (0.04, 0.57)]. CONCLUSIONS:Among females at risk of GDM, an individualized nutritional intervention based on Chinese dietary guidelines provided before the OGTT did not prevent GDM but helped to manage GWG appropriately and improved pregnancy outcomes. This trial was registered on 27 October, 2019, with initial participant enrollment on 5 May, 2020 at ChiCTR as 1900026963 (https://www.chictr.org.cn/searchproj.html?regno=1900026963).

The influence of residential greenness on maternal gestational weight gain (GWG) and fetal intrauterine growth remains understudied. This study examined the impact of residential greenness on GWG and fetal intrauterine growth and assessed the mediating role of GWG. The research included 29406 births in Shanghai, utilizing the normalized difference vegetation index (NDVI) to measure greenness within a 500 m radius (NDVI-500). The analysis employed a generalized linear model to assess the impacts of residental greenness on GWG, fetal growth and birthweight, and a mediation analysis to explore GWG's role between greenness and fetal development. Results indicated that significant benefits were observed with increased greenness, where each 0.1 unit increase in NDVI-500 was associated with reductions of 9.4% (95% CI: 5.5%-13.2%) in the risk of head circumference undergrowth and 8.5% (95% CI: 4.8%-12.2%) in estimated fetal weight undergrowth. Additionally, each 0.1 unit increase in NDVI-500 was associated with reductions of 9.4% (95% CI: 5.1%-13.5%) and 9.2% (95% CI: 6.2%-12.0%) in the risk of inadequate and excessive GWG, respectively. Notably, total GWG mediated 17.5% of the relationship between NDVI-500 and the birth weight. These findings suggest that enhancing residential greenness could be an effective public health strategy to improve pregnancy outcomes by promoting fetal growth and managing GWG, with the GWG partially mediating these benefits.