Limited studies demonstrated the relationships between first-trimester maternal dyslipidemia and adverse pregnancy-offspring complications. This investigation aimed to probe (1) the relationships of first-trimester maternal dyslipidemia with adverse pregnancy and birth outcomes, and (2) the potential influence of first-trimester maternal lipid profiles on offspring growth trajectories. A prospective observational investigation was conducted within the structure of the Tianjin Birth Cohort, in which maternal blood samples were acquired (median at 11th gestational week) to measure lipid levels. Group-based trajectory modeling was employed to classify latent offspring growth trajectories. Poisson regression incorporating robust standard error was employed to analyze the associations of maternal dyslipidemia with adverse pregnancy-offspring complications. First-trimester maternal dyslipidemia significantly increased gestational diabetes mellitus risk after adjustment for confounders (relative risk: 1.36, 1.20–1.54), but did not link to gestational hypertension (1.13, 0.89–1.43) risk. In addition, first-trimester maternal dyslipidemia elevated preterm birth (1.24, 1.03–1.49) and large for gestational age (1.27, 1.12–1.43) risks. However, first-trimester maternal dyslipidemia showed no significant link with either small for gestational age risk (0.83, 0.67–1.03) or offspring growth trajectories from birth to 24 months (lower growth trajectory: 0.99, 0.93–1.06; higher growth trajectory: 0.97, 0.88–1.08). First-trimester maternal dyslipidemia elevated adverse pregnancy and offspring status risks, specifically maternal gestational diabetes mellitus, as well as offspring preterm birth, and large for gestational age, but did not link to maternal gestational hypertension, small for gestational age, or variations in offspring growth trajectories from birth to 24 months.

BACKGROUND:Antenatal mental disorders are associated with maternal and fetal adverse events. Previous studies have been focused on the postpartum period, rather than pregnancy, yet the association of risk factors with prenatal depression and anxiety through pregnancy has been rarely reported. This study aimed to identify the risk factors of prenatal depression and anxiety, and access their potential roles in developing mental disorders during pregnancy. METHODS:This is a prospective study in 6470 participants from the Tianjin Birth Cohort in China (TJBC). The degree of prenatal depression and anxiety was evaluated using a questionnaire of Self-Rating Depression scale (SDS) and Self-Rating Anxiety Scale (SAS), which was given to pregnant women at 15-27 (Stage-2), and 28-41 (Stage-3) gestational weeks. The questionnaire also collected demographic, personal, and lifestyle information. The association of different factors with SDS/SAS score was examined by logistic regression analysis. RESULTS:We observed an overall depression rate of 12.4 % and an overall anxiety rate of 7.7 % during pregnancy in the TJBC. In the Stage-2, the depression rate was 14.5 % and the anxiety rate was 9.5 %. In the Stage-3, the depression rate dropped to 9.7 % while the anxiety rate dropped to 5.3 %. With univariate analysis, we found that age, education, social support, marriage satisfaction, secondhand smoke (SHS), sleeping time and stress were common factors of prenatal mental health. Working status, family income, gravidity, smoking, electronic using, recreational activities were associated with depression risk, whereas BMI, disease history, changing eating habits, and feeding animal were associated with anxiety risk. Using logistic regression, we found that low education level, low social support, low marriage satisfaction, thyroid disfunction, Stage-2(second trimester), and stress were related to prenatal mental health. CONCLUSION:The prevalence anxiety and depression in Tianjin is normal as national level. Age appropriateness, a good education level, sufficient social support, marital satisfaction, normal thyroid function, and absence of stress are associated with relieving depression and anxiety during gestation. However, due to individual difference, expectant mothers should seek professional support and guidance to address their mental health needs during gestation.

Purpose The Bone And MicroBiOme Onset (BAMBOO) study is an ongoing prospective observational cohort study conducted in Tianjin, China, aiming to determine age-appropriate trajectories for microbiome maturation and bone development and to identify the influence of dietary factors in the process.Participants The recruitment started in September 2021 and was completed in February 2023. A total of 1380 subjects were recruited, 690 at birth (group 1) and 690 at 6 months of age (group 2). Groups 1 and 2 will be followed up for 12 months and 36 months, respectively.Findings to date The age of the mothers was 31.1±3.7 (mean±SD), and the birth weight of infants was 3.3±0.5 kg with an incidence of caesarean section 50.4%. Food diary information of the first 100 subjects showed that 64 food items were introduced by 6 months. A pilot microbiome analysis revealed that at the species level, bacterial communities were composed of mostly Bacteroides dorei, Bacteroides vulgatus and Escherichia coli, which were consistent with that of previous reports. Feasibility assessments of breast milk vitamin D and human milk oligosaccharides were validated through certified reference measurements. The early data assessment showed a high reliability of the data generated from this study.Future plans Data collection will be completed in August 2025. Four stage-statistical analyses will be performed as the cohort reaches certain age thresholds before the final report. Analysis of BAMBOO data will be used to develop age-appropriate trajectories for microbiome maturation and bone development for children aged 0–3 years and investigate the contribution of dietary factors in the process.Trial registration number ChiCTR2100049972

Gestational diabetes mellitus (GDM) presents varied manifestations throughout pregnancy and poses a complex clinical challenge. High-depth cell-free DNA (cfDNA) sequencing analysis holds promise in advancing our understanding of GDM pathogenesis and prediction. In 299 women with GDM and 299 matched healthy pregnant women, distinct cfDNA fragment characteristics associated with GDM are identified throughout pregnancy. Integrating cfDNA profiles with lipidomic and single-cell transcriptomic data elucidates functional changes linked to altered lipid metabolism processes in GDM. Transcription start site (TSS) scores in 50 feature genes are used as the cfDNA signature to distinguish GDM cases from controls effectively. Notably, differential coverage of the islet acinar marker gene PRSS1 emerges as a valuable biomarker for GDM. A specialized neural network model is developed, predicting GDM occurrence and validated across two independent cohorts. This research underscores the high-depth cfDNA early prediction and characterization of GDM, offering insights into its molecular underpinnings and potential clinical applications.

Abstract Background: Early childhood growth and development is critical for long term health. Emerging science spotlights the significance of optimal gut microbiome and bone development during this period. The aim of the Bone And MicroBiOme Onset (BAMBOO) study is to determine age-appropriate trajectories for microbiome maturation and bone development, and to identify the influence of dietary factors in the process. This paper is to describe the rationale and study design, and reports study progress. Methods: BAMBOO is an ongoing prospective observational cohort study conducted in Tianjin, China. Children who meet the following requirements are invited to participate in this study: 1) full-term gestational birth (≥ 37 and ≤ 42 weeks); 2) singleton; and 3) signed informed consent by infant’s parents (or his/her legally accepted representative) and agree to fulfill the requirements of the study protocol. The exclusion criteria include pregnancy complication (such as pre-eclampsia, gestational diabetes), bowel disease, or currently participating or having participated in another clinical trial within 4 weeks prior to the start of this cohort. The study is composed of two groups of children: Group 1 includes children from birth to 12 months of age; group 2 includes children from 6 to 36 months of age. Questionnaires are used at different timepoints to collect information on infant feeding practice, medical history, concomitant medication, adverse events/serious adverse events and development benchmarks. Concurrent anthropometric measurements include length/height, weight, and bone measurements. Children’s dietary intake data are collected using 3-day-food diaries. Biological samples (stool, urine, and breastmilk) are also collected at different timepoints. Discussion: Recruitment of Bamboo started in September 2021 and is still ongoing. Data quality assessment and method validation have been conducted using early available samples. This study will provide unprecedented insights on early life microbiome maturation and bone development in Chinese infants and toddlers, and the impact of diet. The results may contribute to evidence-based policy making and inform nutrition healthcare programs for infants and toddlers aiming to benefit long-term health. Trial registration No.: ChiCTR2100049972 (August 16 th , 2021)

Intermittent fasting (IF) is a promising paradigm for weight loss which has been shown to modulate the gut microbiota based on 16S rRNA gene amplicon sequencing. Here, 72 Chinese volunteers with a wide range of body mass index (BMI) participated in a three-week IF program during which an average loss of 3.67 kg body weight accompanied with improved clinical parameters was observed irrespective of initial anthropometric and gut microbiota status. Fecal samples were collected before and after the intervention and subjected to shotgun metagenomic sequencing. De novo assembly yielded 2934 metagenome-assembled genomes (MAGs). Profiling revealed significant enrichment of Parabacteroides distasonis and Bacteroides thetaiotaomicron after the intervention, with inverse correlations between their relative abundances and parameters related to obesity and atherosclerotic cardiovascular diseases (ASCVD). MAGs enriched after the intervention showed high richness and diversity of carbohydrate-active enzymes, with an increased relative abundances of genes related to succinate production and glutamate fermentation.

Abstract Intermittent fasting is a promising paradigm for weight loss which has been shown to modulate the gut microbiota in a couple of populations, yet limited information at the species level is available. Here, 72 Chinese volunteers with a wide range of BMIs participated in a three-week IF program during which an average loss of 3.67 kg body weight accompanied with improved clinical parameters was observed irrespective of initial anthropometric and gut microbiota status. Fecal samples were collected before and after the intervention and subjected to shotgun metagenomic sequencing. De novo assembling yielded 2934 Metagenome-Assembled Genomes (MAGs). Profiling revealed significant enrichment of Parabacteroides distasonis and Bacteroides thetaiotaomicron after the intervention, with inverse correlations between their relative abundances and parameters related to obesity and ACVD. MAGs enriched after the intervention exhibited high richness and diversity of carbohydrate-active enzymes, with an increased relative abundances of genes related to succinate production and glutamate fermentation.

阐述我国母婴出生队列特色生物样本库的建设意义和现状,基于母婴出生队列"样本类型多样、样本来源关联、研究范围广泛"特点及法律规范,从管理体系、设施设备与人员、过程控制、样本利用等角度,结合自动化和信息化手段,探讨我国母婴出生队列特色生物样本库规范化建设及管理方法,助力妊娠期高血压、糖尿病、流产、早产、出生缺陷等发病机制研究,推动母婴特色资源合作与共享.

The pathogenesis of COVID-19 is still elusive, which impedes disease progression prediction, differential diagnosis, and targeted therapy. Plasma cell-free RNAs (cfRNAs) carry unique information from human tissue and thus could point to resourceful solutions for pathogenesis and host-pathogen interactions. Here, we performed a comparative analysis of cfRNA profiles between COVID-19 patients and healthy donors using serial plasma. Analyses of the cfRNA landscape, potential gene regulatory mechanisms, dynamic changes in tRNA pools upon infection, and microbial communities were performed. A total of 380 cfRNA molecules were up-regulated in all COVID-19 patients, of which seven could serve as potential biomarkers (AUC > 0.85) with great sensitivity and specificity. Antiviral ( NFKB1A , IFITM3 , and IFI27 ) and neutrophil activation ( S100A8 , CD68 , and CD63 )–related genes exhibited decreased expression levels during treatment in COVID-19 patients, which is in accordance with the dynamically enhanced inflammatory response in COVID-19 patients. Noncoding RNAs, including some microRNAs (let 7 family) and long noncoding RNAs ( GJA9 - MYCBP ) targeting interleukin (IL6/IL6R), were differentially expressed between COVID-19 patients and healthy donors, which accounts for the potential core mechanism of cytokine storm syndromes; the tRNA pools change significantly between the COVID-19 and healthy group, leading to the accumulation of SARS-CoV-2 biased codons, which facilitate SARS-CoV-2 replication. Finally, several pneumonia-related microorganisms were detected in the plasma of COVID-19 patients, raising the possibility of simultaneously monitoring immune response regulation and microbial communities using cfRNA analysis. This study fills the knowledge gap in the plasma cfRNA landscape of COVID-19 patients and offers insight into the potential mechanisms of cfRNAs to explain COVID-19 pathogenesis.

Background: To investigate the causal link between early-life exposures and long-term health consequences, we established the Tianjin Birth Cohort (TJBC), a large-scale prospective cohort in northern China. Methods: TJBC aims to enroll 10,000 families with follow-ups from pregnancy until children's six year-old. Pregnant women and their spouses were recruited through a three-tier antenatal healthcare system at early pregnancy, with follow-ups at midpregnancy, late pregnancy, delivery, 42 days after delivery, 6 months after delivery, and each year until 6 years old. Antenatal/ neonatal examination, biological samples and questionnaires were collected. Results: From August 2017 to January 2019, a total of 3,924 pregnant women have already been enrolled, and 1,697 women have given birth. We observed the prevalence of gestational diabetes mellitus as 18.1%, anemia as 20.4%, and thyroid hypofunction as 2.0%. In singleton live births, 5.6% were preterm birth (PTB), 3.7% were low birth weight, and 7.3% were macrosomia. Based on current data, we also identified maternal/paternal factors which increased the risk of PTB, including paternal age (OR 1.07; 95% CI, 1.01-1.14 for each year increase), vaginal bleeding during pregnancy (OR 2.82; 95% CI, 1.54-5.17) and maternal early-pregnancy BMI (OR 1.08; 95% CI, 1.01-1.15 for each kg/m2 increase). Conclusion: TJBC has the strength of collecting comprehensive maternal, paternal, and childhood information. With a diverse range of biological samples, we are also engaging with emerging new technologies for multi-omics research. The study would provide new insight into the causal link between macro/micro-environmental exposures of early life and short/long-term health consequences.

We investigated whether screening by whole genome sequencing (WGS) in unselected newborns provides more information of potentially curable or treatable medical conditions than routine newborn screening (NBS). We demonstrated that compared with routine NBS, WGS produced fewer false positive results and identified more actionable pathogenic or likely pathogenic variants in the selective 246 genes. Previously, WGS has been used to identify mutated genes in newborn children with a suspected disease.1 However, sequencing of apparently healthy newborns has remained controversial due to technical concerns and ethical issues.2 In this study, 321 non-pre-selected newborns from a cohort of pregnant women in Qingdao, China were recruited (Table 1). DNA from 303 umbilical cord blood samples and 18 umbilical cords was extracted for 40X WGS. For data interpretation, we selected 251 genes associated with 59 Mendelian disorders, 164 primary immunodeficiency diseases (PIDs) and five pharmacogenetic (PGx) genes, following the guidelines by the Recommended Uniform Screening Panel (RUSP), the International Union of Immunologic Societies (IUIS) Expert Committee for Primary Immunodeficiency, the Dutch Pharmacogenetics Working Group (DPWG), and the Clinical Pharmacogenetics Implementation Consortium (CPIC).3-5 Sequencing protocol, data analysis pipeline, and criteria for sequence variants interpretation following the ACMG/AMP guidelines are described in the Supporting Information. The WGS results were compared with NBS results, including the mandatory checks of hearing impairment and four metabolic diseases, the metabolic testing of 48 inherited metabolic diseases (IMDs), and the genetic screening for 20 hearing loss loci incorporated into the local NBS program in China.6, 7 Among the analysed DNA samples of 321 newborns, the average sequencing depth was 47.42X (28.84X–82.90X) and the average coverage was 99.48% (99.01%–99.89%) (Figure 1A). For the 59 Mendelian disorders, a total of 131 pathogenic or likely pathogenic (P/LP) mutations and 5 pathogenic copy number variations were detected in 107 of the 321 newborns (33.33%), corresponding to 106 carriers of 28 diseases and 1 patient with phenylketonuria (PKU) (Figure 1B and Table 2). The 25.23% of newborns (n = 81) carried one P/LP mutations, and 7.17% and 0.93% of newborns (n = 23 and n = 3) carried two or three P/LP mutations, respectively. Hearing loss, methylmalonic acidemia (MMA), primary congenital hypothyroidism (CH), and PKU were diseases with the most carriers, while GJB2 (28/321, 8.72%), MMACHC (11/321, 3.43%), DUOX2 (10/321, 3.12%), PAH (8/321, 2.49%) and SLC26A4 (8/321, 2.49%) were the top five genes with the highest carrier frequencies of P/LP mutations (Table 2). For the 164 PIDs, 9 heterozygous P/LP variants in 6 genes were identified in 9 newborns (2.80%), all in a heterozygous state (Table 2). Four newborns were shown to carry heterozygous variant of unknown significance (VUS) in the gene SLC25A13 (c.2T>C, p.M1T), which was predicted as start loss and likely affecting the initiator methionine of the SLC25A13 mRNA. Two newborns carried a VUS in ASS1(c.-4C>T, p.?). Although these VUSs were not included in the final report to the participants, follow-up of the children with VUSs will be conducted till 3 years of age. Sanger sequencing confirmed 143 out of 145 mutations identified by WGS, resulting in an accuracy of 98.62%. Carriers of SMN1 mutations were validated by multiplex ligation-dependent probe amplification and real-time quantitative PCR, showing that five out of the six predicted carriers were true. Of the 321 newborns, 312 (97.20%) had the results of 48 IMDs screening and genetic hearing loss screening on 20 loci, which identified one newborn with PKU and one infant with increased blood level of isovalerylcarnitine (Table 1). In addition, 18 carriers harbouring 20 pathogenic mutations causing hearing impairment were detected by genetic hearting loss screening, albeit all 321 children passed the physical hearing screening at hospital (Supporting Information). The newborn WGS also identified the PKU case and 18 hearing loss carriers (Figure 2A). However, the child with increased level of isovalerylcarnitine was confirmed to be a carrier of 3-methylcrotonyl-CoA carboxylase deficiency by WGS. In addition, WGS identified two infants carrying compound heterozygous P/LP variants in GJB2 (Figure 3) and four children carrying pathogenic mutations in MT-RNR1 (c1095T > C), suggesting an increased risk of late-onset deafness or drug-induced hearing loss, respectively. Although currently non-symptomatic, the two newborns with GJB2 variants were scheduled to undergo hearing tests every 6 months, and the four newborns with the m.1095T mutation in MT-RNR1 were advised to avoid using aminoglycosides. Interestingly, we observed that 313 newborns (97.51%) carried at least one actionable PGx variant (Figure 1C). This result is in line with a European 44 000 biobank participants study, where 99.8% of the participants had a genotype associated with increased risks to at least one medication.8 Furthermore, we found three common PGx variants in the Qingdao cohort, CYP2D6*10 (48.60%), NUDT15*3 (13.08%) and UGT1A1*6 (21.18%) (Figure 2B and Table 3), that showed significant frequency differences as compared to East Asian populations (p < 0.05). An important aspect when screening for disorders in a given population is the use of a matched control database as variants can be highly specific for a given ethnic group.9 Most databases published to date are based on individuals of European descent and many populations have limited or poor representation. Limitations of the current study are the small sample size and restricted metabolic tests. A large-scale NBS effort is needed to validate our findings and fully investigate the treatable or curable medical conditions in newborns. The technical challenge of newborn WGS is to screen genes with high homology due to the misalignment of short-read sequencing. Therefore, the customized pipeline is needed to improve the accuracy and sensitivity of SNVs at genes with high-level homology. Albeit the present cost and turnaround time of WGS is several times more than the present NBS methods, in the forseeable future the pitfalls of WGS cost and turnaround time will likely facilitate the application of newborn WGS in NBS programs. In our study, selective identification of genomic data, where therapeutic options are available, did not violate the Wilson–Jungner criteria10. Our work provides a basis for future research on expanding screening genes and diseases in newborn screening program. Given adequate cost-effectiveness, WGS should be considered in future newborn screening programs. Further discussion of the interpretation accuracy and ethical use of genomic information needs to take place on a global scale. We appreciate the participation of the volunteers and their families. Without their support, this work would not have been possible. This work was also supported by the China National GeneBank (CNGB). This study was funded by the National Natural Science Foundation of China (No.31800765), the Shenzhen Municipal Government of China (JCY20170817145047361) and the Guangdong Provincial Key Laboratory of Genome Read and Write (No. 2017B030301011). The authors declare no conflict of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Background: The aim of this study is to investigate potentially curable or treatable medical conditions in unselected newborns using genomic sequencing(GS). Methods: 321 newborns from a cohort of pregnant women from Qingdao, China, underwent high-depth GS (average 47.42 fold), with the approval of the ethics committee. 61 Mendelian Diseases, 151 Primary Immunodeficiency Diseases(PID) and 5 DPWG recommeded Essential pharmacogenetic(PGx) genes were analyzed. Results : 121 Mendelian pathogenic or likely pathogenic variants associated with 31 inherited diseases were detected, among these hearing loss, congenital hypothyroidism, methylmalonic acidemia, methylmalonic acidemia with homocystinuria, phenylketonuria(PKU) and benign hyperphenylalaninemia accounted for half of the carrier variants. Three children with compound heterozygous variants at GJB2 and PAH were confirmed by Sanger sequencing. Follow-up of the three families confirmed that one child was diagnosed with PKU and two children with GJB2 variants were scheduled to undergo hearing loss testing every six months after genetic counceling due to the nature of incomplete penetrance of hearing loss. 11 heterozygous pathogenic/ likely pathogenic variants in eight PID genes were identified in 11 infants. All 321 newborns carried at least one variant at the five DPGW recommended PGx genes. Codeine and clopidogrel require more attention in giving prescription for 25% and 8% of newborns have a decreased function of CYP2D6 and CYP2C19 enzymes respectively. Conclusions: Our study is the largest to date using GS to sequence unselected newborns. The results suggest that using GS may be a suitable method for screening newborns for variants in a large number of disease associated genes.

Background The gut microbiota plays important roles in modulating host metabolism. Previous studies have demonstrated differences in the gut microbiome of T2D and prediabetic individuals compared to healthy individuals, with distinct disease-related microbial profiles being reported in groups of different age and ethnicity. However, confounding factors such as anti-diabetic medication hamper identification of the gut microbial changes in disease development. Method We used a combination of in-depth metagenomics and metaproteomics analyses of faecal samples from treatment-naïve type 2 diabetic (TN-T2D, n=77), pre-diabetic (Pre-DM, n=80), and normal glucose tolerant (NGT, n=97) individuals to investigate compositional and functional changes of the gut microbiota and the faecal content of microbial and host proteins in Pre-DM and treatment-naïve T2D individuals to elucidate possible host-microbial interplays characterising different disease stages. Findings We observed distinct differences characterizing the gut microbiota of these three groups and validated several key features in an independent TN-T2D cohort. We also demonstrated that the content of several human antimicrobial peptides and pancreatic enzymes differed in faecal samples between three groups, such as reduced faecal level of antimicrobial peptides and pancreatic enzymes in TN-T2D. Interpretation Our findings suggest a complex, disease stage-dependent interplay between the gut microbiota and the host and emphasize the value of metaproteomics to gain further insight into interplays between the gut microbiota and the host. Funding National Key Research and Development Program of China, No. 2017YFC0909703, Shenzhen Municipal Government of China, No. JCYJ20170817145809215, and National Natural Science Foundation of China, No. 31601073.

The relationship between dyslipidemia and type 2 diabetes mellitus (T2D) has been extensively reported, but the global lipid profiles, especially in the East Asia population, associated with the development of T2D remain to be characterized. Liquid chromatography coupled to tandem mass spectrometry was applied to detect the global lipidome in the fasting plasma of 293 Chinese individuals, including 114 T2D patients, 81 prediabetic subjects, and 98 individuals with normal glucose tolerance (NGT). Both qualitative and quantitative analyses revealed a gradual change in plasma lipid features with T2D patients exhibiting characteristics close to those of prediabetic individuals, whereas they differed significantly from individuals with NGT. We constructed and validated a random forest classifier with 28 lipidomic features that effectively discriminated T2D from NGT or prediabetes. Most of the selected features significantly correlated with diabetic clinical indices. Hydroxybutyrylcarnitine was positively correlated with fasting plasma glucose, 2-hour postprandial glucose, glycated hemoglobin, and insulin resistance index (HOMA-IR). Lysophosphatidylcholines such as lysophosphatidylcholine (18:0), lysophosphatidylcholine (18:1), and lysophosphatidylcholine (18:2) were all negatively correlated with HOMA-IR. The altered plasma lipidome in Chinese T2D and prediabetic subjects suggests that lipid features may play a role in the pathogenesis of T2D and that such features may provide a basis for evaluating risk and monitoring disease development.