BACKGROUND:Early prediction of gestational diabetes mellitus (GDM) enables timely interventions but remains challenging, particularly in women living without obesity who are often overlooked by standard screening methods. This exploratory analysis identifies early pregnancy biomarkers that show associations with GDM up to 8-12 weeks earlier than the established diagnostic timeframe. METHODS:A retrospective nested case-control study was conducted at Tianjin Central Hospital of Gynecology Obstetrics. After applying the predefined inclusion and exclusion criteria and removing cases with missing blood samples, a total of 136 women were included in the final analysis, comprising 56 women with GDM and 80 non-GDM controls. These data were used to develop multiple machine learning models, including random forest, logistic regression, SVM, XGBoost, and KNN. The performance of these models was assessed by AUC, sensitivity, specificity, positive predictive value, and negative predictive value in an independent validation set. RESULTS:The random forest classifier achieved the best performance with an AUC of 0.992 in the validation set, indicating excellent sensitivity and specificity. The model incorporated six measurable variables: age, BMI, and four cytokines (IL-1β, IL-10, IL-17A, and IL-4) participating in immune regulation in pregnancy. CONCLUSIONS:GDM can be predicted with high accuracy early in pregnancy, even among women living without obesity. This study highlights the value of integrating immunological biomarkers with clinical characteristics and machine learning for proactive risk stratification. Although promising, our findings warrant validation in larger, multiethnic cohorts to ensure generalizability.

BackgroundComplement C3 is a key effector molecule of the innate complement system, which participates in inflammatory responses, immune regulation and the maintenance of metabolic homeostasis. Consistency and evidence grade regarding the association between serum C3 levels and polycystic ovary syndrome (PCOS) remain controversial. This systematic meta-analysis aims to assess changes of C3 levels in PCOS patients.MethodWe systematically searched PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), VIP Chinese Science and Technology Journal Database (VIP) and Wanfang Database for studies concerning PCOS and C3, from database inception to December 31, 2025. Literature screening, data extraction and risk of bias assessment using the Newcastle-Ottawa Scale (NOS) were independently performed by two investigators. Sensitivity analysis was performed by sequentially omitting each individual study to verify the robustness of the pooled results. Funnel plots were adopted for preliminary evaluation of publication bias. Subgroup analysis was used to explore potential effect modifiers. All statistical analyses were conducted using R software (version 4.6.0) to guarantee the scientific validity and reliability of the findings.ResultsA total of 6 studies meeting the predefined inclusion criteria were included, enrolling 915 individuals. C3 levels were higher in PCOS patients than controls (SMD = 0.73, 95% CI: 0.54–0.93), with moderate heterogeneity (I²=47.1%, P = 0.092). No significant difference was observed between subgroups. Sensitivity analysis confirmed the robustness of the overall association.ConclusionThis meta-analysis suggests that circulating C3 levels are elevated in PCOS. However, due to the observational design and limited evidence, these findings are exploratory. Prospective studies are needed to validate this association.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251121390.

IntroductionIntellectual disability, autosomal dominant 29 is a rare disorder resulting from pathogenic variants of SETBP1 gene with no specific mutation hotspot identified. Systematic descriptions of new cases are crucial for understanding the genotypic and phenotypic spectrums of the disease.Case presentationA pregnant woman was referred to the prenatal diagnosis center at our hospital because she has an intellectual disability and has previously given birth to a child with intellectual disabilities. Karyotype, CNV-seq and whole-exome sequencing (WES) were employed to investigate the potential genetic issues in the family. The SETBP1 NM_015559.2: c.2425C>T (p.Gln809*) nonsense variant was found in the proband and mother, who were diagnosed with MRD29. Amniocentesis and genetic analysis (CNV-seq and sanger sequencing for mutation site) were performed as fetal cortical abnormalities and subependymal cystic area presented by ultrasonic examination at 25 + 5 gestational weeks. The genetic analysis confirmed the SETBP1 c.2425C>T (p.Gln809*) nonsense mutation in the fetus. The parents terminated the pregnancy at 30 + 4 gestational weeks.ConclusionThe SETBP1 NM_015559.2: c.2425C>T (p.Gln809*) nonsense variant is pathogenic and SETBP1 haploinsufficiency may be associated with fatal cortical abnormalities. More prenatal clinical data is helpful for a better productive decision making and patient management.

Diabetes is a major concern in healthcare worldwide and is detrimental to mothers and fetuses during pregnancy. However, half of the women were unaware of hyperglycemia before pregnancy, and there is no consensus on their identification during pregnancy. We aim to understand the role that diagnostic timing plays in perinatal outcomes. This was a multicenter retrospective study of all pregestational diabetes mellitus (PGDM) women who delivered from January 2021 to June 2023. Diagnoses were made before or during gestation. Characteristics and outcomes were compared among stages, and logistic regression was performed to explore the relationship between adverse outcomes and the diagnostic timing. This study included 2,818 women; 1188 (42.2%) were self-aware before pregnancy, and 286 (10.1%), 1208 (42.9%), and 136 (4.8%) were diagnosed in the first, second, and third trimesters, respectively. Maternal body mass index, hypertensive disorders during pregnancy, glucose profile, large-for-gestational-age (LGA), etc., differed among stages (all P < 0.05). Logistic regression revealed that PGDM diagnosed during any trimester was significantly associated with an increased risk of macrosomia (aOR = 2.632, 1.502, 2.314; all P < 0.05). However, the risk of LGA decreased if the diagnosis was based on the 2 h value of the oral glucose tolerance test (OGTT) alone in the second trimester (aOR = 0.608, 95% CI: 0.444-0.831). No relationship existed between diagnostic timing and neonatal birth defects or hypoglycemia (both P > 0.05). PGDM identified during pregnancy was significantly associated with an increased risk of fetal overgrowth. The role of the 2 h-OGTT alone in diagnosis warrants further exploration. PGDM screening is essential for the entire gestational period.

Spontaneous preterm labor (SPTL) is a major cause of neonatal mortality and severe complications. T cells play a crucial role in mediating inflammation and immune tolerance at the maternal–fetal interface. T helper 17 cells (Th17, pro-inflammatory) and regulatory T cells (Treg, anti-inflammatory) are two subsets of CD4+ T cells with opposite functions, and their balance is important for maintaining immune homeostasis. Since infection and inflammation represent prominent factors responsible for the pathogenesis of SPTL, Th17/Treg imbalance at the maternal–fetal interface may trigger proinflammatory responses, potentially leading to SPTL. In this review, evidence from both clinical cases of SPTL and animal models indicates the presence of Th17/Treg imbalance in both peripheral blood and the maternal–fetal interface. Additionally, interleukin-6 (IL-6), interleukin-1β (IL-1β), and interleukin-8 (IL-8) have been involved in the pathogenesis of inflammation-induced SPTL, suggesting that Th17/Treg imbalance may have relevance to and be involved in the pathogenic process of SPTL. Moreover, the presence of Th17/Treg imbalance in risk factors for SPTL, such as autoimmune diseases and bacterial infections, further supports this connection indirectly. Although predictive models and interventional strategies related to SPTL have been explored, there is currently insufficient evidence to establish a direct causal relationship between Th17/Treg imbalance and the onset of SPTL.

OBJECTIVE:To examine whether glycemic level modifies the association between gestational weight gain (GWG) and pregnancy outcomes in type 2 diabetes-complicated pregnancies. RESEARCH DESIGN AND METHODS:This multicenter retrospective study stratified 1,642 pregnant women with diabetes by third-trimester glycemic control. Associations between excessive GWG (eGWG) and pregnancy outcomes were analyzed by group. RESULTS:Although birth weight and odds of macrosomia and cesarean delivery were higher for all women with eGWG relative to those with adequate GWG, the effect estimates for birth weight and macrosomia were significantly higher with suboptimal glycemic control compared with optimal control (birth weight increase: 361.04 vs. 126.07 g, respectively, P = 0.007; adjusted odds ratio for macrosomia: 4.26 vs. 2.73, P = 0.002; cesarean delivery: 1.86 vs. 1.52, P = 0.738). CONCLUSIONS:Overly stringent weight control should be treated with caution if optimal glycemic control is not achieved.

In 2019, preterm births (PTB) accounted for approximately 0.66 million deaths globally. PTB is also associated with a significantly higher risk of mortality and long-term complications for newborns. Long-term studies associated several factors, including disruption of immune tolerance and inflammation, with PTB. However, the pathogenesis of PTB remains unclear. Gonadal steroid hormones are critical for pregnancy maintenance and regulation of immune and inflammatory responses. However, it is not clear how unbalanced gonadal steroid hormones, such as imbalanced estrogen/androgen or estrogen/progesterone contribute to PTB. In this review, we discuss how gonadal steroid hormones mediate dysfunction in immune tolerance and inflammatory responses, which are known to promote the occurrence of PTB, and provide insight into PTB prediction.

Abstract Objective: To systematically analyze the genetic features of fetal renal abnormalities and the prenatal characteristics of 17q12 microdeletion syndrome. Methods: We retrospective analysis of fetal diagnosed with renal abnormalities from January 2016 to August 2022. Chromosome test, fetal renal abnormalities and pregnancy outcomes were performed in a descriptive analysis. Results: 141 patients (4.5%) showed abnormal renal development and 26 patients (26/141) with hyperechogenic kidneys (HCK), 14 (14/26) cases showed chromosomal abnormalities, 12 patients were 17q12 microdeletion syndrome. In addition, there were 14 17q12 microdeletion syndrome among the patients, and 12 fetal had hyperechogenic kidneys (HCK), 7 fetal were verified by couples, 5 fetal had new mutations, and 2 fetal inherited from parents. After excluding patients with HCK, the polycystic kidney has a higher rate of chromosomal abnormalities compared to polycystic renal dysplasia and renal dysplasia. The chromosomal of isolated horseshoe kidney, hydronephrosis, ectopic kidney and unilateral kidney often were normal, and the chromosomal abnormalities rate was increased when combined with other abnormalities. Conclusion: Fatal HCK was closely related to 17q12 microdeletion syndrome. The chromosome test result of patients with isolated polycystic kidney dysplasia, kidney dysplasia, horseshoe kidney, hydronephrosis, kidney deficiency, and ectopic kidney were mostly normal. Prenatal diagnosis was recommended, specifically in the fetus had non-isolated renal abnormalities. Most patients with normal chromosomes or uncertain clinical significance choose to produce, but adverse pregnancy outcomes were not excluded. This study will provide more data support for fetal renal abnormalities.

Abstract Objective: To systematically analyze the genetic features of fetal renal abnormalities and the prenatal characteristics of 17q12 microdeletion syndrome. Methods: We retrospectively analyzed fetuses diagnosed with renal abnormalities between January 2016 to August 2022 using CNV-Seq and SNP. The pregnancy outcomes were followed up for 2 months after birth. All results have been descriptively analyzed. Results: Among a total of 141 patients (4.5%) with renal dysplasia, 26 patients (26/141) had enhanced renal echo (hyperechogenic kidney; HCK), of which 10 were isolated HCK and 16 were non-isolated HCK. It was found that results of chromosome examination were abnormal in 14 (14/26) patients, of which 12 were diagnosed with 17q12 microdeletion syndrome. Moreover, there were 14 cases of 17q12 microdeletion syndrome in all patients with renal dysplasia, including 12 cases with HCK and 2 cases with other renal abnormalities. Chromosome family verification revealed that 5 fetuses had new mutations and 2 fetuses had inherited mutations. After excluding HCK patients, the incidence of chromosomal abnormalities in patients with polycystic kidneys was higher than that in patients with polycystic kidney dysplasia and renal dysplasia. The chromosomes in patients with isolated horseshoe kidney, hydronephrosis, ectopic kidney, and unilateral kidney were usually normal. Nevertheless, the incidence of chromosomal abnormalities increases when combined with other abnormalities. Most patients with normal chromosomes or uncertain clinical significance choose to give birth and had a good prognosis, but adverse pregnancy outcomes could not be ruled out. Conclusion: It was found that HCK was closely related to 17q12 microdeletion syndrome. Chromosomal examinations of patients with other renal abnormalities (isolated polycystic kidney dysplasia, renal dysplasia, horseshoe kidney, hydronephrosis, renal deficiency, ectopic kidney) were mostly normal. In combination with abnormal results, prenatal diagnosis is recommended. This study provides more evidential data that supports the relationship between fetal kidney and chromosomal abnormalities.

Steroid hormones, including progestagens, estrogens, androgens, corticosteroids, and their precursor cholesterol, perform essential functions in the successful establishment and maintenance of pregnancy and normal fetal development. As the core endocrine organ at the prenatal stage, the human placenta is involved in the biosynthesis, metabolism, and delivery of steroid hormones. Steroidogenic pathways are tightly regulated by placenta-intrinsic cytochrome P450 and hydroxysteroid dehydrogenase. However, the relationship between placental steroidogenic enzyme expression and adverse pregnancy outcomes is controversial. In this review, we summarize the possible upstream regulatory mechanisms of placental steroidogenic enzymes in physiologic and pathophysiologic states. We also describe the human placental barrier model and examine the potential of single-cell sequencing for evaluating the primary functions and cellular origin of steroidogenic enzymes. Finally, we examine the existing evidence for the association between placental steroidogenic enzyme dysregulation and adverse pregnancy outcomes.

Abstract Objective: To systematically analyze the genetic features of fetal renal abnormalities and the prenatal characteristics of 17q12 microdeletion syndrome. Methods: We retrospectively analyzed fetuses diagnosed with renal abnormalities between January 2016 to August 2022 using CNV-Seq and SNP. The pregnancy outcomes were followed up for 2 months after birth. All results have been descriptively analyzed. Results: Among a total of 141 patients (4.5%) with renal dysplasia, 26 patients (26/141) had enhanced renal echo (hyperechogenic kidney; HCK), of which 10 were isolated HCK and 16 were non-isolated HCK. It was found that results of chromosome examination were abnormal in 14 (14/26) patients, of which 12 were diagnosed with 17q12 microdeletion syndrome. Moreover, there were 14 cases of 17q12 microdeletion syndrome in all patients with renal dysplasia, including 12 cases with HCK and 2 cases with other renal abnormalities. Chromosome family verification revealed that 5 fetuses had new mutations and 2 fetuses had inherited mutations. After excluding HCK patients, the incidence of chromosomal abnormalities in patients with polycystic kidneys was higher than that in patients with polycystic kidney dysplasia and renal dysplasia. The chromosomes in patients with isolated horseshoe kidney, hydronephrosis, ectopic kidney, and unilateral kidney were usually normal. Nevertheless, the incidence of chromosomal abnormalities increases when combined with other abnormalities. Most patients with normal chromosomes or uncertain clinical significance choose to give birth and had a good prognosis, but adverse pregnancy outcomes could not be ruled out. Conclusion: It was found that HCK was closely related to 17q12 microdeletion syndrome. Chromosomal examinations of patients with other renal abnormalities (isolated polycystic kidney dysplasia, renal dysplasia, horseshoe kidney, hydronephrosis, renal deficiency, ectopic kidney) were mostly normal. In combination with abnormal results, prenatal diagnosis is recommended. This study provides more evidential data that supports the relationship between fetal kidney and chromosomal abnormalities.

Abstract Preeclampsia (PE) is the most common medical complication during pregnancy and the second leading cause of maternal death worldwide. However, a better predictive model of PE remains to be explored. A total of 15 severe preeclampsia (sPE) and 75 healthy control patients were included in this study. Patient data was obtained from September 2019 to September 2021. Nuchal translucency (NT) and crown‐rump length (CRL) of the fetus were acquired by ultrasound. Maternal blood samples were collected at 11+0 to 13+6 weeks of gestation. Chemiluminescent immunoassays were used to detect serum testosterone (T) and estradiol (E2) levels. Time‐resolved fluorescence analysis was used to examine the levels of serum pregnancy‐associated plasma protein A (PAPPA) and β‐human chorionic gonadotrophin (β‐HCG) protein. The sPE group exhibited increased T levels, and decreased E2 levels and E2/T ratios from 11 to 14 weeks of gestation, compared with the control group. E2 and the E2/T ratio showed positive linear correlation with CRL in pregnant women. Body‐mass‐index (BMI), T, and E2 were determined to be the main factors that affected the occurrence of sPE at the 12‐week gestation period time point. The receiver operating characteristic (ROC) curve revealed that the AUC of the E2/T ratio was .717. The imbalanced T and E2 levels in the patients had a specific intrinsic relevance with sPE, which suggests them as novel predictors of the sPE.