Preeclampsia (PE) remains a major cause of maternal and fetal morbidity, necessitating accurate prediction tools. This prospective study evaluated urinary misfolded proteins (MPs), detected by the point-of-care CercaTest RED device, for short-term PE prediction in 365 women with suspected PE at ≥ 20 weeks with 1207 longitudinal urine samples. MPs alone showed predictive value (AUC 0.770) for PE within one week. A multivariate model integrating MPs with clinical parameters (mean arterial pressure, antihypertensive treatment, prior PE history, and gestational age-adjusted BMI change [ΔBMI/GA]) further improved performance (AUC 0.937). The mean gestational age at PE diagnosis was 36.7 ± 2.5 weeks. The model offered high negative predictive value (97.7%) to rule out imminent PE and a positive predictive value of 54.0% to support rule-in decisions, and maintained robustness across gestational age groups (< 34 vs. ≥34 weeks). The integration of urinary MPs with clinical data provides a practical, non-invasive tool for short-term PE risk stratification, with potential for convenient monitoring in low-resource settings. Trial registration: ChiCTR2300074878. https//www.chictr.org.cn/showproj.html?proj=202096.

Abstract Introduction The ARRIVE trial first demonstrated that elective induction of labour (IOL) at 39 weeks in low-risk pregnancies reduced the likelihood of caesarean section (CS) without compromising perinatal safety; however, the generalizability of these findings remains debated, leading to uncertainty in clinical practice. The LIRIC trial aims to evaluate whether 39-week elective IOL reduces CS rates compared with expectant management, while exploring its impact on infant neurodevelopment and multi-omics profiles. Methods and analysis This is a single-centre, open-label, randomized controlled trial in China. A total of 1,074 low-risk pregnant women (nulliparous or multiparous) will be randomly assigned (1:1 ratio) to either 39-week IOL or expectant management. The primary outcome is the caesarean section (CS) rate. Secondary outcomes include a composite of severe neonatal morbidity and perinatal mortality and infant neurodevelopmental scores (Bayley-4 and ASQ-3), among others. Data analysis will follow the Intention-to-Treat (ITT) principle. Biospecimen will be collected for metagenomic and metabolomic analyses, with results to be reported separately. Ethics and dissemination The protocol has been approved by the Ethics Committee of Women’s Hospital, School of Medicine, Zhejiang University. Informed consent will be obtained from all participants. Results will be disseminated via peer-reviewed journals, and standardized infant developmental reports will be provided to participants to enhance study benefit. Trial registration number NCT07082530 .

The transplacental transfer of xenobiotics, particularly in an enantioselective manner, is a critical and evolving area of developmental toxicology. Pregnant women, as a highly vulnerable population, are frequently exposed to pervasive chiral chemicals that can cross the placenta, with the placenta serving as an enantioselective barrier. Despite significant research on enantioselective transfer of xenobiotics using various models (in vivo, ex vivo, and in vitro), a comprehensive understanding of the underlying mechanisms of xenobiotics-plasma protein binding remains lacking. This review provides a state-of-the-art synthesis of the characteristics and mechanisms governing the enantioselective transplacental transfer of pharmaceuticals, pesticides, and industrial additives-representative chiral xenobiotics of significant public health concern. We highlight how xenobiotics, acting as ligands, interact with proteins, influencing enantioselective transfer through key processes such as plasma protein binding, transporter-mediated biotransport, and enzyme-catalyzed biotransformation. Notably, the binding of xenobiotics to human serum albumin (HSA) rather than α1-acid glycoprotein (AGP) is shown to primarily inhibit the transmembrane transport of small molecules. Whereas limited docking studies suggest Sudlow site II as a pivotal site for enantioselective binding. Additionally, P-glycoprotein (permeability glycoprotein, P-gp) and cytochrome P450 (CYP450) are important in determining the enantiomeric distribution between maternal and fetus. Pathological conditions may also modify transplacental transfer efficiencies (TTEs). Future research employing advanced techniques, such as isotopic tracing, affinity chromatography, high-resolution screening, and machine learning, will be essential to further elucidate enantiomeric transport mechanisms and their implications for fetal development.

Observational epidemiological studies have demonstrated that maternal exposure to air pollution increases the risk of adverse pregnancy outcomes. However, interactions among multiple environmental exposures remain underexplored. In this study, we performed an epidemiological analysis on 147,979 pregnant women recruited from nine provinces in southeastern China between 2013 and 2023, focusing on the risk of low birth weight (LBW). We found that the critical exposure windows for PM2.5 and ozone (O3) extend from six months prior to conception through the end of second trimester, with hazard ratio of HR = 1.152 (95 % confidence interval [CI]: 1.128-1.177) per 10-μg/m3 incremental PM2.5 exposure and HR = 1.028 (95 % CI: 1.024-1.031) per 10-ppb increase in O3. Our estimates indicate that in 2021, approximately 47,500 (95 % uncertainty interval [UI]: 41,200-53,600) live-born LBW infants nationwide in China could be attributed to ambient air pollution, declining from 79,800 (95 % UI: 71,700-87,900) in 2002. We observed statistically significant synergistic risk effects, neglecting which could lead to an underestimation of 11,600 (95 % UI: 9,300-13,900) LBW cases. Although air pollution-associated LBW burden is decreasing, the rapidly rising LBW prevalence remains a significant public health concern, particularly as China is implementing the "three-child policy". Therefore, our study offers precisely quantified, evidence-based policy guidance for safeguarding reproductive health.

The distribution and migration of SCCP concentrations in surface soil, groundwater and the atmosphere in a petrochemical factory.

Background Preeclampsia (PE) is one of the most common hypertensive diseases, affecting 2%-8% of all pregnancies. The high maternal and fetal mortality rates of PE are due to a lack of early identification of affected pregnant women that would have led to closer monitoring and care. Recent data suggest that misfolded proteins might be a promising biomarker for PE prediction, which can be detected in urine samples of pregnant women according to their congophilia (aggregated) characteristic. Objective The main purpose of this trial is to evaluate the value of the urine congophilia-based detection of misfolded proteins for the imminent prediction of PE in women presenting with suspected PE. The secondary objectives are to demonstrate that the presence of urine misfolded proteins correlates with PE-related maternal or neonatal adverse outcomes, and to establish an accurate PE prediction model by combining misfolded proteins with multiple indicators. Methods At least 300 pregnant women with clinical suspicion of PE will be enrolled in this prospective cohort study. Participants should meet the following inclusion criteria in addition to a suspicion of PE: ≥18 years old, gestational week between 20+0 and 33+6, and single pregnancy. Consecutive urine samples will be collected, blinded, and tested for misfolded proteins and other PE-related biomarkers at enrollment and at 4 follow-up visits. Clinical assessments of PE status and related complications for all participants will be performed at regular intervals using strict diagnostic criteria. Investigators and participants will remain blinded to the results. Follow-up will be performed until 42 days postpartum. Data from medical records, including maternal and fetal outcomes, will be collected. The performance of urine misfolded proteins alone and combined with other biomarkers or clinical variables for the prediction of PE will be statistically analyzed. Results Enrollment started in July 2023 and was still open upon manuscript submission. As of March 2024, a total of 251 eligible women have been enrolled in the study and enrollment is expected to continue until August 2024. Results analysis is scheduled to start after all participants reach the follow-up endpoint and complete clinical data are collected. Conclusions Upon completion of the study, we expect to derive an accurate PE prediction model, which will allow for proactive management of pregnant women with clinical suspicion of PE and possibly reduce the associated adverse pregnancy outcomes. The additional prognostic value of misfolded proteins is also expected to be confirmed. Trial Registration Chinese Clinical Trials Registry ChiCTR2300074878; https://www.chictr.org.cn/showproj.html?proj=202096 International Registered Report Identifier (IRRID) PRR1-10.2196/54026

Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic disease that occurs during mid-to-late pregnancy and is associated with various adverse pregnancy outcomes, including intrauterine fetal demise. However, since the underlying cause of ICP remains unclear, there is an ongoing debate on the phenotyping criteria used in the diagnostic process. Here, we identified single- and multi-symptomatic ICP (ICP-S and ICP-M) in 104,221 Chinese females from the ZEBRA maternity cohort, with the objective of exploring the risk implications of the two phenotypes on pregnancy outcomes and from environmental exposures. We employed multivariate binary logistic regression to estimate confounder-adjusted odds ratios and found that ICP-M was more strongly associated with preterm birth and low birth weight compared to ICP-S. Throughout pregnancy, incremental exposure to PM2.5, O3, and greenness could alter ICP risks by 17.3%, 12.5%, and -2.3%, respectively, with more substantial associations observed with ICP-M than with ICP-S. The major scientific advancements lie in the elucidation of synergistic risk interactions between pollutants and the protective antagonistic effects of greenness, as well as highlighting the risk impact of preconceptional environmental exposures. Our study, conducted in the context of the "three-child policy" in China, provides epidemiological evidence for policy-making to safeguard maternal

Background Strong and synchronized contractions that occur in the last stage of pregnancy are essential for onset of labor. In clinics, the lack of effective description of these characteristics results in inaccurate prediction of the onset of labor. The commonly used contraction monitoring device tocodynamometer (TOCO) detects contractions with relatively high specificity but is unable to quantify the strength and synchrony. The electrohysterography (EHG) quantifies the myoelectric activities that trigger contractions of muscle cells under the electrodes. Therefore, multiple channel EHG signals are well suited for characterizing the strength and synchrony of uterine contractions via their spatiotemporal pattern. Object: The purpose of this study was to provide quantitative descriptions of the contraction characteristics and to investigate their significance for predicting the spontaneous onset of labor in nulliparous women. Study Design: 100 pregnant women with a gestational age of more than 37 weeks were recruited for the study. Multichannel EHG and tocodynamometer recordings were performed simultaneously for 46 of them, both during pregnancy and during labor (defined a time to onset of labor (TTL) less than 24 h). Contractions were identified from the TOCO recordings, and then the frequency and duration of contractions were determined. The multichannel EHG segments under the identified contractile time windows were used to calculate the strength and level of synchrony. Statistical analyses were carried to demonstrate the difference of these variables between the pregnant and labor groups. Multivariate logistic regression was created to provide obstetricians with an assessment tool in predicting spontaneous onset of term labor. Results The frequency, duration, strength, and level of synchrony of uterine contractions for 46 pregnant women during their 37 weeks of gestation to the onset of labor were quantified. All constructed features in labor, with the exception of concordance correlation-based synchrony \(\:\psi\:\), showed statistically significant differences from those in pregnant phase, with degree of synchrony described by the sample entropy SamEn being the strongest feature for distinguishing pregnant and labor (0.5154 ± 0.1720 vs. 0.3555 ± 0.1422, \(\:p=0.00001\)). The multivariate logistic regression model constructed from these features showed high significance in identifying the onset of spontaneous labor in nulliparous women, with an AUC value of 0.80. Conclusion The contraction properties in terms of frequency, duration, strength, and level of synchrony have been quantitated. Continuous observations on 46 pregnant women throughout their pregnancy demonstrated statistically significant difference between contractions in pregnant and labor phase, which enabled a prediction model on spontaneous onset of labor in term nulliparous women.

Background Preeclampsia (PE) is one of the most common hypertensive diseases, affecting 2%-8% of all pregnancies. The high maternal and fetal mortality rates of PE are due to a lack of early identification of affected pregnant women that would have led to closer monitoring and care. Recent data suggest that misfolded proteins might be a promising biomarker for PE prediction, which can be detected in urine samples of pregnant women according to their congophilia (aggregated) characteristic. Objective The main purpose of this trial is to evaluate the value of the urine congophilia-based detection of misfolded proteins for the imminent prediction of PE in women presenting with suspected PE. The secondary objectives are to demonstrate that the presence of urine misfolded proteins correlates with PE-related maternal or neonatal adverse outcomes, and to establish an accurate PE prediction model by combining misfolded proteins with multiple indicators. Methods At least 300 pregnant women with clinical suspicion of PE will be enrolled in this prospective cohort study. Participants should meet the following inclusion criteria in addition to a suspicion of PE: ≥18 years old, gestational week between 20+0 and 33+6, and single pregnancy. Consecutive urine samples will be collected, blinded, and tested for misfolded proteins and other PE-related biomarkers at enrollment and at 4 follow-up visits. Clinical assessments of PE status and related complications for all participants will be performed at regular intervals using strict diagnostic criteria. Investigators and participants will remain blinded to the results. Follow-up will be performed until 42 days postpartum. Data from medical records, including maternal and fetal outcomes, will be collected. The performance of urine misfolded proteins alone and combined with other biomarkers or clinical variables for the prediction of PE will be statistically analyzed. Results Enrollment started in July 2023 and was still open upon manuscript submission. As of March 2024, a total of 251 eligible women have been enrolled in the study and enrollment is expected to continue until August 2024. Results analysis is scheduled to start after all participants reach the follow-up endpoint and complete clinical data are collected. Conclusions Upon completion of the study, we expect to derive an accurate PE prediction model, which will allow for proactive management of pregnant women with clinical suspicion of PE and possibly reduce the associated adverse pregnancy outcomes. The additional prognostic value of misfolded proteins is also expected to be confirmed. Trial Registration Chinese Clinical Trials Registry ChiCTR2300074878; https://www.chictr.org.cn/showproj.html?proj=202096 International Registered Report Identifier (IRRID) PRR1-10.2196/54026

>Streptococcal toxic shock syndrome（STSS） is an acute, life-threatening illness caused by invasive group A Streptococcus（iGAS）. The initial manifestations of STSS are atypical, and may progress to shock, multiple organ dysfunction syndrome（MODS）, and disseminated intravascular coagulation（DIC） quickly. In the United States, the incidence of STSS is 0.2/100,000 individuals per year, with a mortality rate of 36%. The rate of GASrelated STSS in pregnant women is 89 times higher than that in nonpregnant women of the same age. [1] A few cases of STSS during pregnancy have been reported. Herein, we report a case of a multigravida who developed STSS in late pregnancy, with intrauterine fetal death（IUFD） and a rescued mother. We also reviewed the relevant literature to improve comprehension of the disease.

Ingestion of breast milk represents the primary exposure pathway for endocrine-disrupting chemicals (EDCs) in newborns. To elucidate the associated risks, it is essential to quantify EDC levels in both breast milk and infant urine. This study measured the concentrations of 13 EDCs, including parabens (methyl paraben (MP), ethyl paraben (EP), propyl paraben (PP), iso-propyl paraben, butyl paraben, and iso-butyl paraben), bisphenols (bisphenol A (BPA), bisphenol F, bisphenol S, bisphenol AF, and bisphenol Z), triclosan (TCS), and triclocarban, in breast milk and infant urine to assess their potential health effects and endocrine disruption risks. In total, 1 014 breast milk samples were collected from 20 cities across China, along with 144 breast milk samples and 134 urine samples from a mother-infant cohort in Hangzhou. The EDCs were detected using ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry. Endocrine-disrupting potency was evaluated using a predictive method based on EDC affinity for 15 hormone receptor proteins. The toxicological priority index (ToxPi), incorporating population exposure data, was employed to assess health risks associated with exposure to multiple EDCs. Among the 13 EDCs, MP, EP, PP, BPA, and TCS were detected in over 50 % of breast milk samples, with the highest median concentrations observed for MP (0.37 ng/mL), EP (0.29 ng/mL), and BPA (0.17 ng/mL). Across the 20 cities, 0 %-40 % of infants had a hazard index (HI) exceeding 1. Based on affinity prediction analysis and estimated exposure, cumulative endocrine disruption risk intensity was ranked as MP > TCS > BPA > EP > PP. This research highlights the extensive exposure of Chinese infants to EDCs, offering a detailed analysis of their varying endocrine disruption potencies and underscoring the significant health risks associated with EDCs in breast milk.

Background Accurate prenatal recognition of discordant fetal growth in twins is critical for deciding suitable management strategies. We explored the predictive value of the level of maternal second-trimester placental growth factor (PLGF) as a novel indicator of discordant fetal growth. Methods A total of 860 women pregnant with twins were enrolled, including 168 women with monochorionic twins (31 cases of discordant fetal growth and 137 without) and 692 with dichorionic twins (79 cases of discordant fetal growth and 613 without). Maternal second-trimester PLGF concentrations were measured via immunofluorescence. Results Maternal second-trimester PLGF levels were significantly lower in women pregnant with twins who subsequently developed discordant fetal growth than in those who did not (monochorionic twin pregnancy: P < 0.001; dichorionic twin pregnancy: P < 0.001). A 3–4 fold difference in median PLGF concentrations was detected between the two groups with both monochorionic and dichorionic twin pregnancies. Maternal second-trimester PLGF levels were significantly correlated with birth weight differences (monochorionic twin pregnancy: r = − 0.331, P < 0.001; dichorionic twin pregnancy: r = − 0.234, P < 0.001). A receiver operating characteristic curve was used to evaluate the predictive efficiency. In monochorionic twin pregnancies, the area under the curve (AUC) was 0.751 (95% confidence interval [CI]: 0.649–0.852), and the cutoff value was 187.5 pg/mL with a sensitivity of 77.4% and specificity of 71.0%. In dichorionic twin pregnancies, the AUC was 0.716 (95% CI; 0.655–0.777), and the cutoff value was 252.5 pg/mL with a sensitivity of 65.1% and specificity of 69.6%. Based on the above cutoff values, univariate and multivariate logistic regression analyses were performed to calculate the odds ratios (OR) for the PLGF levels. After adjustment for potential confounding factors, low PLGF concentrations still significantly increased the risk of discordant fetal growth (monochorionic twin pregnancy: adjusted OR: 7.039, 95% CI: 2.798–17.710, P < 0.001; dichorionic twin pregnancy: adjusted OR: 4.279, 95% CI: 2.572–7.120, P < 0.001). Conclusions A low maternal second-trimester PLGF level is considered a remarkable risk factor and potential predictor of discordant fetal growth. This finding provides a complementary screening strategy for the prediction of discordant fetal growth and offers a unique perspective for the subsequent research in this field.

Immune rejection caused by mismatches in human leucocyte antigens (HLAs) remains a major obstacle to the success of allogeneic cell therapies. Current strategies for the generation of 'universal' immune-compatible cells, particularly the editing of HLA class I (HLA-I) genes or the modulation of proteins that inhibit natural killer cells, often result in genomic instability or cellular cytotoxicity. Here we show that a beta(2)-microglobulin super-enhancer (B2M-SE) that is responsive to interferon-gamma is a critical regulator of the expression of HLA-I on mesenchymal stromal cells (MSCs). Targeted epigenetic repression of B2M-SE in MSCs reduced the surface expression of HLA-I below the threshold required to activate allogenic T cells while maintaining levels sufficient to evade cytotoxicity mediated by natural killer cells. In a humanized mouse model, the epigenetically edited MSCs demonstrated improved survival by evading the immune system, allowing them to exert enhanced therapeutic effects on LPS-induced acute lung injury. Targeted epigenetic repression of B2M-SE may facilitate the development of off-the-shelf cell sources for allogeneic cell therapy.

China's "three-child policy", implemented in response to population aging, has made the protection of maternal and infant health an urgent priority. In this environmental and medical big-data era, the Zhejiang Environmental and Birth Health Research Alliance (ZEBRA) maternity cohort was established with the aim of identifying risk factors for perinatal morbidity and mortality from the perspectives of both observational epidemiology and experimental etiology. Compared with conventional birth cohorts, the inclusion of a maternity cohort allows greater scope for research and places an emphasis on maternal health. In particular, it allows us to focus on pregnant women with a history of pregnancy-related illnesses and those planning to have a second or third child. There are currently many pressing issues in perinatal health, including the risk associations between exogenous together with endogenous factors and the occurrence of perinatal abnormalities, pregnancy complications, and adverse pregnancy outcomes. It is crucial to explore the interaction between environmental exposures and genetic factors affecting perinatal health if we are to improve it. It is also worthwhile to assess the feasibility of the early stage prediction of major perinatal abnormalities. We hope to study this in the ZEBRA cohort and also seek nationwide and international collaborations to establish a multicenter cohort consortium, with the ultimate goal of contributing epidemiological evidence to literature and providing evidence-based insights for global maternal and child healthcare.

Organophosphate esters (OPEs) are extensively manufactured and used in China. Whether exposure to OPEs during pregnancy increases the risk of gestational diabetes mellitus (GDM) is unknown. Between 2011 and 2012, a case-control study including 130 and 67 women with and without GDM, respectively, was conducted in Hangzhou, China. The levels of 10 OPEs in maternal serum samples at delivery were quantified, and the relationships between the OPE concentrations and GDM risk were investigated. The results show that in all participants, tri-n-butyl phosphate (TNBP, median: 2.02 ng/mL) was the most common OPE present in the serum, followed by tri-phenyl phosphate (TPHP, median: 1.74 ng/mL) and tri-iso-butyl phosphate (median: 1.68 ng/mL). With one-unit elevation in the tris (2-chloroethyl) phosphate, TNBP, TPHP, and tris (2-butoxy ethyl) phosphate (TBOEP) concentrations in maternal serum, 1-h glucose levels increased by 0.19 (95% confidence interval (CI): −0.01, 0.29), 0.11 (95% CI: −0.18, 0.62), 0.29 (95% CI: 0.12, 0.58), and 0.20 units (95% CI: 0.01, 0.44), respectively. In addition, a unit increase in TBOEP levels in maternal serum was associated with an increase of 0.26 units (95% CI: 0.09, 0.61) in 2-h glucose levels. After adjusting for covariate factors, serum TNBP (odds ratio (OR) = 2.07; 95% CI: 1.27, 3.41), TBOEP (OR = 2.63; 95% CI: 1.68, 4.11), and TPHP (OR = 1.03; 95% CI: 1.05, 1.51) concentrations were associated with GDM incidence in pregnant women. Overall, TNBP, TBOEP, and TPHP exposure during pregnancy is associated with GDM risk and increased glucose levels.

Background: Human breast milk is a primary route of exposure to perfluoroalkyl substances (PFAS) in infants. To understand the associated risks, the occurrence of PFAS in human milk and the toxicokinetics of PFAS in infants need to be addressed. Objectives: We determined levels of emerging and legacy PFAS in human milk and urine samples from Chinese breastfed infants, estimated renal clearance, and predicted infant serum PFAS levels. Methods: In total, human milk samples were collected from 1,151 lactating mothers in 21 cities in China. In addition, 80 paired infant cord blood and urine samples were obtained from two cities. Nine emerging PFAS and 13 legacy PFAS were analyzed in the samples using ultra high-performance liquid chromatography tandem mass spectrometry. Renal clearance rates (CLrenals) of PFAS were estimated in the paired samples. PFAS serum concentrations in infants (<1 year of age) were predicted using a first-order pharmacokinetic model. Results: All nine emerging PFAS were detected in human milk, with the detection rates of 6:2 Cl-PFESA, PFMOAA, and PFO5DoDA all exceeding 70%. The level of 6:2 Cl-PFESA in human milk (median concentration=13.6 ng/L) ranked third after PFOA (336 ng/L) and PFOS (49.7 ng/L). The estimated daily intake (EDI) values of PFOA and PFOS exceeded the reference dose (RfD) of 20 ng/kg BW per day recommended by the U.S. Environmental Protection Agency in 78% and 17% of breastfed infant samples, respectively. 6:2 Cl-PFESA had the lowest infant CLrenal (0.009mL/kg BW per day), corresponding to the longest estimated half-life of 49 y. The average half-lives of PFMOAA, PFO2HxA, and PFO3OA were 0.221, 0.075, and 0.304 y, respectively. The CLrenals of PFOA, PFNA, and PFDA were slower in infants than in adults. Conclusions: Our results demonstrate the widespread occurrence of emerging PFAS in human milk in China. The relatively high EDIs and half-lives of emerging PFAS suggest potential health risks of postnatal exposure in newborns. https://doi.org/10.1289/EHP11403

Phthalate metabolites are widely present in humans and can have many adverse effects on pregnant women. To date, many studies on the effects of phthalate metabolites on the risk of gestational diabetes mellitus (GDM) have been published, but the findings of these studies are controversial. We conducted a case-control study to quantify the concentrations of seven phthalate metabolites in the serum of pregnant women and to investigate their association with the risk of GDM and blood glucose levels in pregnant women. Therefore, 201 serum samples (139 pregnant women with GDM and 62 control serum samples) were collected from Hangzhou, China, between 2011 and 2012. The results showed that mono butyl phthalate (MBP; mean = 4.08 ng/mL) was the most abundant phthalate metabolites in human serum, followed by mono (2-ethylhexyl) phthalate (MEHP; mean = 1.28 ng/mL) and mono isobutyl phthalate (MiBP; mean = 1.20 ng/mL). The other results indicated significant associations between MBP (β = 2.24, 95 % confidence interval (CI): 1.02, 5.07, P = 0.050) and MiBP (β = 1.84, 95 % CI: 1.03, 3.31, P = 0.041) concentrations in human serum and the incidence of GDM. Moreover, serum MBP (β = 0.40, 95 % CI: 0.10, 0.70, P = 0.010) and MiBP levels (β = 0.18, 95 % CI: 0.010, 0.35, P = 0.047) in humans were positively associated with 2-hour blood glucose levels. Our study provides affirmative evidence on previously inconsistent findings that MBP and MiBP exposure may increase the risk of GDM in pregnant women.

Poly- and perfluoroalkyl substances (PFAS), which have been found in high concentrations in maternal serum, have the potential to impair glucose metabolism in pregnant women. However, the effects of PFAS exposure on the risk of gestational diabetes mellitus (GDM) remain inconsistent. In the current investigation, a case-control study involving 135 patients with GDM and 69 controls was conducted in Hangzhou, China. We determined the concentrations of 17 PFAS in maternal serum from each participant and elucidated the associations between those concentrations and the risk of GDM. Among the 17 PFAS, perfluorooctanesulfonate (median 7.53 and 7.44 ng/mL) was the predominant PFAS in both cases and controls, followed by perfluorooctanoic acid (PFOA; median 5.22 and 5.03 ng/mL) and 6:2 chlorinated perfluoroalkyl ether sulfonate (6:2 Cl-PFESA; median 2.58 and 2.42 ng/mL). Conditional logistic regression analysis showed that the maternal serum continuous levels of PFOA, perfluorononanoic acid (PFNA), perfluorohexanesulfonate (PFHxS), and 6:2 Cl-PFESA were significantly associated with the GDM risk, with adjusted odds ratios (ORs) of 1.84 (95% confidence interval (CI): 1.26, 3.51), 1.47 (1.17, 3.29), 1.33 (1.72, 3.48), and 1.34 (1.17, 2.53), respectively. In the adjusted model, the ORs of GDM for increasing tertiles of PFOA, PFNA, PFHxS, and 6:2 Cl-PFESA significantly increased. The adjusted ORs (95% CI) were 3.38 (2.16, 6.89), 2.61 (1.26, 5.40), 3.46 (1.64, 6.30), and 3.50 (1.62, 6.91) at the highest concentrations of PFOA, PFNA, PFHxS, and 6:2 Cl-PFESA, respectively. These results suggest that higher PFAS exposure, reflected in serum PFAS concentrations, was associated with GDM incidence in pregnant women.

The Zhejiang Environmental and Birth Health Research Alliance (ZEBRA) established a maternity cohort to investigate the relationship between perinatal abnormalities and various risk factors among the Chinese maternal population. The primary aim of ZEBRA is to explore the feasibility of early-stage risk prediction and the forecast of adverse perinatal symptoms and gestational outcomes. The cohort is ambidirectional, with a retrospective arm tracking 6,275 pregnant females enrolled between 2013 and 2016, and a prospective arm recruiting 112,414 participants since the baseline year of 2017. The current ZEBRA maternity cohort database comprises a diverse range of sociodemographic features, physiological characteristics, medical history, therapeutic interventions, and measurements of environmental exposures. Going forward, the cohort will continue to enrol a wider range of participants and collect an even more extensive array of features. ZEBRA is seeking collaborations with both national and international multi-cohort studies to contribute to the field of epidemiology, and provide valuable evidence-based insights for global maternal and child healthcare.