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Low birth weight and anemia are significant public health challenges in developing countries. This study seeks to evaluate the relationship between hemoglobin levels during the first and second trimesters of pregnancy and the occurrence of low birth weight, while accounting for potential confounding factors. This multi-center cross-sectional study was conducted among all pregnant women with COVID-19 and with no history of receiving the COVID-19 vaccine who delivered in public and private hospitals in three counties, Mahabad, Miandoab, Bukan in Iran, using routinely collected maternity and health data on pregnancies. Hemoglobulin levels were measured during the first (6-10th weeks) and second (24-28th weeks) trimesters of pregnancy, and pregnancy outcomes were recorded in the health information system. Hb levels were categorized into four groups as follows: ≥110 g/L, 100-109 g/L, 90-99 g/L, and < 90 g/L for the first trimester and ≥ 105 g/L, 100-104 g/L, 90-99 g/L, and < 90 g/L for the second trimester. Multivariable logistic regression analysis determined the association between hemoglobin levels during pregnancy and low birth weight. P-values < 0.05 were considered statistically significant. A total of 385 mothers with COVID-19 were included. The mean age of COVID-19 pregnant women was 30.01 ± 6.24 years. After multivariable adjustment, Hb levels < 110 g/L in the first trimester had a significant association with low birth weight [OR, 4.13; (95% CI 2.11-8.10)]. Morevoer, Hb levels < 105 g/L in the second trimester was a significant association with low birth weight [OR:3.91; (95% CI:1.98-7.75)]. Maternal anemia during pregnancy, including first and second trimesters, was a significant association with Low birth weight even after adjusting for common confounders. Effective management and monitoring of anemia in pregnant women, particularly in low- and middle-income countries, are crucial for preventing low birth weight., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The association between inflammatory indices from peripheral blood cell in early pregnancy and the risk of gestational diabetes mellitus (GDM) is unclear., Methods: This was a retrospective study involving the medical data of 15,807 pregnant women who gave birth in 2019. Data were collected from the medical records and analyzed. The pregnant women's age, educational level, pre-pregnancy body weight, height, parity, family history of diabetes, lipid profile, blood pressure were recorded during 11 ~ 13 + 6 pregnancy weeks. We collected and measured several easily accessible systemic inflammatory indices from peripheral blood cell count, including Neutrophils, Lymphocytes, Monocytes, MHR (monocyte count/HDL-C), SII (platelet count ×neutrophil count/lymphocyte count ) and SIRI (neutrophil count ×monocyte count/lymphocyte count), and we analyzed their association with the risk of developing GDM., Results: In the present study, a total of 15,807 women were included, including 2,355 (14.9%) women diagnosed with GDM. Women who were diagnosed with GDM showed markedly lower level of monocyte count and higher level of neutrophil and lymphocyte counts. The GDM group showed relatively lower level of SIRI, while no significant differences were found between GDM group and non-GDM group in MHR or SII. After adjusting for potential confounding factors, we observed a significant association between monocyte counts, MHR and the risk of developing GDM, and the risk tended to decrease with increasing levels of monocyte counts and MHR., Conclusion: The present study revealed that in early pregnancy, monocyte count and MHR have great potential as early diagnostic markers of GDM., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval for the current study was obtained from Clinical Research Ethics Committee of the International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University [(GKLW)2018-29] Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Consent to participate: Not applicable., (© 2025. The Author(s).)

Background: Although insulin resistance has been associated with unfavorable pregnancy outcomes, the ability of non-insulin-based insulin resistance indicators to predict adverse pregnancy outcomes has yet to be thoroughly understood. The study aims to investigate the association and predictability of triglyceride glucose-body mass index (TyG-BMI), a biomarker of non-insulin-based insulin resistance, with the risks of adverse pregnancy outcomes., Method: The retrospective study included 1,136 subjects. Group-based trajectory modeling (GBTM) was employed to identify the TyG-BMI index trajectory. Logistic regression, restricted cubic spline (RCS) regression, and subgroup analysis were used to assess the association between the TyG-BMI index trajectory and the first-trimester TyG-BMI index with the risks of adverse pregnancy outcomes. Receiver-operating characteristic (ROC) curve analysis and the DeLong test were utilized to evaluate the prediction ability of the first-trimester TyG-BMI index for adverse pregnancy outcomes., Results: GBTM revealed three distinct trajectories of the TyG-BMI index. Using the "low-stable" trajectory as a reference, the "high-stable" trajectory was independently associated with an increased risk of gestational diabetes mellitus (GDM) (aOR = 2.01, 95% CI 1.20-3.37), hypertensive disorders of pregnancy (HDP) (aOR = 6.05, 95% CI 3.00-12.18), and large for gestational age (LGA) (aOR = 2.83, 95% CI 1.28-6.25). The highest quartile of the first-trimester TyG-BMI index was independently linked to elevated GDM (aOR = 3.27, 95% CI 1.92-5.59), HDP (aOR = 9.26, 95% CI 3.19-26.88), and LGA (aOR = 2.26, 95% CI 1.00-5.09)risks. Additionally, the third quartile of the first-trimester TyG-BMI index had 2.21-fold increased odds of GDM (aOR = 2.21, 95% CI 1.27-3.82). The first-trimester TyG-BMI index demonstrated a significant linear association with GDM, HDP, SGA, and LGA risks. Compared to the TyG-BMI index trajectory, the highest quartile of the first-trimester TyG-BMI index exhibited a stronger association with the risks of GDM and HDP (aOR = 3.09 and 7.39, respectively). Furthermore, according to the ROC curve, the first-trimester TyG-BMI index outperformed the TyG index and triglyceride/high-density lipoprotein cholesterol (TG/HDL-c) ratio at predicting HDP (0.726 [0.650-0.801] vs. 0.603 [0.527-0.679] vs. 0.615 [0.537-0.693]), LGA (0.619 [0.540-0.699] vs. 0.534 [0.454-0.613] vs. 0.540 [0.458-0.622]), and GDM (0.664 [0.622-0.705] vs. 0.632 [0.588-0.676] vs. 0.604 [0.560-0.649]). According to the DeLong test, the first-trimester TyG-BMI index was a more valuable predictor for LGA and HDP compared to TyG index and TG/HDL-c ratio., Conclusion: Higher levels of first-trimester TyG-BMI and a "high-stable" trajectory were linked to a greater risk of adverse pregnancy outcomes. Furthermore, as compared to TyG and TG/HDL-c, the first-trimester TyG-BMI index is a valuable predictor for HDP, GDM, and LGA., Competing Interests: Declarations. Ethics approval and consent to participate: The study adhered to the Declaration of Helsinki. It was part of a pregnancy cohort approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-Sen University (Approval number: [2022]717). Participants were required to provide written informed consent before enrolling in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

There are conflicting results on the association between maternal vitamin D concentrations during pregnancy and respiratory outcomes for their offspring. However, published studies have mainly focused on the second and third trimesters of pregnancy or on high-risk population. The main objective of this study was to evaluate the association between vitamin D plasma concentrations in the first trimester (T1) of pregnancy and effective specific airway resistance (sR eff ) for children aged 5 to 6. Secondary objectives were to evaluate this association in the third trimester (T3) and in cord blood as well as the association between vitamin D plasma concentration and interrupter resistance (Rint), bronchiolitis, asthma, and allergen sensitization at the same time points. This multicenter study included 140 children born from women enrolled in the FEPED cohort. Associations between sR eff and maternal vitamin D plasma concentration at T1, T3 of pregnancy, and in cord blood were assessed. sR eff was analyzed according to in-utero and postnatal exposure to tobacco smoke and the occurrence of an episode of bronchiolitis before 6 months of age. The impact of maternal vitamin D status on the secondary outcomes was similarly assessed. sR eff values were not associated with the maternal vitamin D status at T1 and T3, nor asthma status or allergen sensitization., Conclusion: In a cohort of young children, airway resistance and asthma were not associated with early vitamin D deficiency during pregnancy., Trial Registration: This study is registered with the ClinicalTrials.gov identifier NCT03229317., What Is Known: • There are conflicting results on the association between maternal vitamin D concentrations during pregnancy and respiratory outcomes for their offspring. However, published studies have mainly focused on the second and third trimesters of pregnancy or on high-risk population., What Is New: • In a cohort of 5- to 6-year-old children assessed prospectively, there was no significant difference in sReff or any other lung function measurements depending on maternal vitamin D status during the first trimester of pregnancy., Competing Interests: Declarations. Ethics approval: This study was approved by the Comité de Protection des Personnes CPP Ile de France VI on (CPP/32–17). Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s).)

Aim: To compare the first-trimester combined inflammatory markers between pregnant women diagnosed with ulcerative colitis (UC) and healthy pregnant women. Furthermore, to investigate the predictive value of these markers for adverse obstetric outcomes in pregnant women affected by UC., Methods: In this retrospective study, data were collected from pregnant women with UC who gave birth at our hospital between January 2021 and May 2024 and from a control group of healthy pregnant women. A comparison was made between the two groups in terms of their demographic characteristics, neonatal outcomes, and the values of the first-trimester neutrophil-to-lymphocyte ratio (NLR), systemic inflammation index (SII), systemic inflammatory response index (SIRI), and aggregated index of systemic inflammation (AISI). Furthermore, the relationship between these combined inflammatory markers and adverse obstetric outcomes in pregnant women with UC was investigated., Results: No notable discrepancy was observed between the UC group and the control group with respect to SIRI and AISI. The first-trimester NLR and SII values were observed to be higher in the UC group in comparison to the control group. The data indicated that pregnant women with UC who experienced poor obstetric outcomes exhibited elevated levels of NLR, SII, SIRI, and AISI during the first trimester. In the ROC analysis, the predictive capacity of all four parameters for poor obstetric outcomes in UC patients was statistically significant., Conclusion: There is an association between elevated combined inflammatory markers in the first trimester and poor obstetric outcomes in pregnant women with UC., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To develop a model based on maternal serum liquid chromatography tandem mass spectrometry (LC-MS/MS) proteins to predict spontaneous preterm birth (sPTB)., Methods: This nested case-control study used the data from a cohort of 2053 women in China from July 1, 2018, to January 31, 2019. In total, 110 singleton pregnancies at 11-13 +6 weeks of pregnancy were used for model development and internal validation. A total of 72 pregnancies at 20-32 weeks from an additional cohort of 2167 women were used to evaluate the scalability of the model. Maternal serum samples were analyzed by LC-MS/MS, and a predictive model was developed using machine learning algorithms., Results: A novel predictive panel with four proteins, including soluble fms-like tyrosine kinase-1, matrix metalloproteinase 8, ceruloplasmin, and sex-hormone-binding globulin, was developed. The optimal model of logistic regression had an AUC of 0.934, with additional prediction of sPTB in second and third trimester (AUC = 0.868)., Conclusion: First-trimester modeling based on maternal serum LC-MS/MS identifies pregnant women at risk of sPTB, which may provide utility in identifying women at risk at an early stage of pregnancy before clinical presentation to allow for earlier intervention., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: The relationship between serum ferritin levels and the risk of gestational diabetes mellitus (GDM) remains unclear. This study aimed to investigate the association between serum ferritin levels and the incidence of GDM., Methods: We conducted a prospective cohort study involving 10,871 pregnant women from the China Birth Cohort Study. Serum ferritin levels were measured using the direct chemiluminescence method in the first and second trimesters. Baseline serum ferritin levels were categorized into five groups according to quintiles in the first trimester, and trimester-specific median values were used to divide serum ferritin levels into four subgroups. GDM was determined by a 75 g oral glucose tolerance test at 24-28 weeks of gestation. Multivariate modified Poisson regression was performed to estimate the independent relationship between serum ferritin levels and the incident GDM., Results: The median serum ferritin level in the first trimester was 57.7 ng/mL, and 13.5% of participants developed GDM. After multivariate adjustment, the RRs and 95% CIs for incident GDM across baseline serum-ferritin quintiles were 1.099 (0.940-1.285), 1.228 (1.055-1.430), 1.186 (1.018-1.383) and 1.179 (1.017-1.367), respectively. Furthermore, participants with low serum ferritin levels in the first trimester that increased to high levels in the second trimester (RR = 1.376, 95% CI: 1.169-1.612) and those with consistently high serum ferritin levels in the first and second trimesters (RR = 1.351, 95% CI: 1.185-1.541) had a significantly increased risk of GDM., Conclusions: Changes in serum ferritin levels are independent risk factors for GDM. These findings underscore the importance of maintaining iron metabolism at an appropriate level during early to mid-pregnancy to reduce the risk of developing GDM., Competing Interests: Declarations. Ethics approval and consent to participant: Ethics approval was provided by Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital (approval number: 2018-KY-003-02). Informed, written consent was obtained from of all the participants. CBCS adhered to the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Clinical trial number: Not applicable., (© 2025. The Author(s).)

Background: Lower maternal insulin sensitivity during pregnancy is associated with greater fetal adiposity. Physical activity can improve insulin sensitivity, but it is not known if physical behaviours influence the known association of maternal insulin sensitivity with offspring adiposity. This study aimed to investigate the moderating impact of physical behaviours on this association., Methods: Pregnant women (n = 812) from the Gen3G cohort were recruited during the first trimester of pregnancy and followed until delivery. At the first (V1) and second trimester (V2) hospital visits, Gen3G staff measured anthropometry, and participants reported sleep duration as well as leisure physical activity and sedentary behaviour via lifestyle questionnaires. We used plasma glucose and insulin values from the 75 g oral glucose tolerance test at V2 to calculate insulin sensitivity using the Matsuda index. We recorded birthweight from electronic medical records. Among a subset of neonates (n = 265), trained research staff measured skinfold thickness using a calibrated skinfold caliper following standardized protocols to estimate neonatal adiposity. Linear regression analyses assessed the association of insulin sensitivity with birthweight z-score and sum of neonatal skinfold thickness, adjusting for maternal age, race/ethnicity, gravidity, smoking, with and without adjustment for maternal body mass index at V1. We evaluated moderation by physical activity, sedentary behaviour, or nighttime sleep duration using interaction terms and stratified analyses for the association of maternal insulin sensitivity with offspring birthweight and with offspring adiposity., Results: Lower Matsuda index was associated with higher birthweight z-score (ß±SE= -0.180 ± 0.056, p = 0.001) and with higher sum of skinfold thickness (neonatal adiposity) (ß±SE=-0.877 ± 0.383, p = 0.02) in fully adjusted models. The association between Matsuda index and sum of skinfold thickness was weaker in women with higher levels of physical activity at V2 ([high ≥ 1.26 kcal/kg/day] ß±SE=-0.15 ± 0.65) compared to women with lower levels [low < 1.26 kcal/kg/day] ß±SE=-1.36 ± 0.51, P-interaction = 0.01). We also observed potential interactions of sleep and sedentary behaviour at V2 with Matsuda index for the association with birthweight z-score. We did not observe effect modification by levels of physical behaviours assessed at V1., Conclusion: The association between lower insulin sensitivity and higher neonatal adiposity was attenuated in women with higher physical activity levels in the second trimester, independent of maternal body mass index., Competing Interests: Declarations. Ethics approval and consent to participate: This project was approved by the Clinical and organizational ethics committee of the CIUSSS de l’Estrie - CHUS and all participants provided written consent. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: There is no evidence to suggest that an association exists between the remnant cholesterol (RC) to high-density lipoprotein cholesterol (HDL-C) ratio and gestational diabetes mellitus (GDM). In this study, the RC/HDL-C ratio during the first trimester was examined as a potential indicator of the onset of GDM during the second trimester., Methods: This was a secondary analysis of data from a Korea-based prospective cohort study. The study involved 582 women within 14 weeks of pregnancy who were examined between November 2014 and July 2016 at two Korean hospitals. RC was calculated as total cholesterol (TC) minus the sum of low-density lipoprotein cholesterol (LDL-C) and HDL-C. The RC/HDL-C ratio was determined by dividing the RC content by the HDL-C content. The RC/HDL-C ratio and GDM occurrence were investigated utilizing a binary logistic regression model, various sensitivity analyses, and subgroup analyses. Additionally, the RC/HDL-C ratio was evaluated using receiver operating characteristic (ROC) analysis., Results: The average age of the pregnant women was 32.07 ± 3.78 years, and the RC/HDL-C ratio had a median value of 0.39. The prevalence of GDM was 6.01%. There was a positive association between the RC/HDL-C ratio and the incidence of GDM after adjusting for potential confounding variables (odds ratio: 21.78, 95% confidence interval [CI]: 3.55-133.73, P < 0.001). Furthermore, this association was validated by subgroup and sensitivity analyses. The results indicated that the RC/HDL-C ratio was a robust predictor of GDM, with an area under the ROC curve of 0.795 (95% CI: 0.723-0.868). The optimal threshold value was 0.45, with a sensitivity of 71.4% and a specificity of 75.3%. Compared with traditional lipid markers, including LDL-C, HDL-C, triglycerides, TC, and the emerging marker RC, the RC/HDL-C exhibited higher diagnostic efficacy., Conclusion: There is an increased risk of GDM associated with higher levels of the RC/HDL-C ratio between 12 and 14 weeks of gestation, independent of traditional risk factors. The RC/HDL-C ratio is more effective in diagnosing GDM than traditional lipid markers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Sheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The balance of omega-6/omega-3 ( n -6/ n -3) is crucial for proper brain function as they have opposite physiological roles., Objectives: To analyze the association between maternal serum ratios of n -6/ n -3 in the first and third trimesters of pregnancy and the neurodevelopment of their children in the early days after birth in the population of Northern Spain's Mediterranean region., Methods: Longitudinal study in which 336 mother-child pairs participated. Mother serum concentrations of long-chain polyunsaturated fatty acids (LCPUFAs), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) were determined. Sociodemographic, clinical, lifestyle habits, and obstetrical variables were collected. The Bayley Scales of Infant and Toddler Development (BSID-III) was used to assess infant neurodevelopment. Multiple linear regression models adjusting for confounding factors were performed., Results: In the third trimester, a higher maternal n -6/ n -3 ratio was negatively associated with infant motor development (β = -0.124, p = 0.023). Similarly, higher ARA/DHA ratios were negatively associated with total motor (β = -2.005, p = 0.002) and fine motor development (β = -0.389, p = 0.001). No significant associations were observed in the first trimester nor for the ARA/EPA ratio in the third trimester., Conclusions: Our findings indicate that an elevated n -6/ n -3 ratio and ARA/DHA ratio in the third trimester of pregnancy are associated with poorer motor development outcomes in infants. These results highlight the importance of optimizing maternal fatty acid balance during pregnancy to support fetal neurodevelopment, suggesting a need for further research to verify these associations and elucidate underlying mechanisms.

Iron deficiency in pregnancy remains underdiagnosed despite professional society recommendations for first-trimester complete blood count (CBC) screening. To determine the effectiveness of the CBC hemoglobin and mean corpuscular volume (MCV) to identify iron deficiency in pregnancy, we conducted a retrospective analysis of 20,550 pregnancies from 2009 to 2022 at the University of California, San Francisco, obstetrics clinics. A total of 16,547 (80.5%) pregnant individuals had first-trimester screening CBC; 345 (2.1%) had a coincident ferritin test. Hemoglobin level less than 11 g/dL and MCV level less than 80 fL each had sensitivity of only 30% (95% CI, 20-41%) to detect first-trimester iron deficiency (ferritin level less than 30), corresponding to a negative likelihood ratio of 0.90 (95% CI, 0.77-1.05) and 0.85 (95% CI, 0.73-0.99), respectively. More than 50% of the 1,749 women with documented iron deficiency anytime during pregnancy were neither anemic nor microcytic at the time of diagnosis., Competing Interests: Financial Disclosure Andrew Leavitt serves on the advisory boards for hemophilia gene therapy for BioMarin and Pfizer. The other authors did not report any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study aimed to investigate the association between maternal factors and first-trimester biophysical and biochemical markers with small for gestational age (SGA) neonates in twin pregnancies (TwPs)., Methods: Single-center retrospective cohort study of TwPs followed from January 2010 to December 2022 at a tertiary perinatal center, Portugal. Maternal and pregnancy characteristics, mean arterial pressure, pregnancy-associated plasma protein-A (PAPP-A), β-human chorionic gonadotropin (β-HCG), and uterine artery pulsatility index (UtA-PI) were analyzed. Univariable, multivariable logistic regression (LR) and receiver-operating characteristic curve analyses were performed. The main outcome measures considered were: SGA < 3rd, < 5th and < 10th percentile, the composite outcome of SGA combined with preterm birth (PTB) (< 32, < 34, and < 36 weeks)., Results: 572 TwPs were included, 450 (78.7%) DC and 122 (21.3%) MC. TwPs affected with SGA < 3rd, < 5th or < 10th percentiles were 120/572 (20.9%), 157/572 (27.4%) and 190/572 (33.2%), respectively. SGA < 3rd percentile was associated with a higher rate of PTB, 59.0% of cases < 32 weeks, OR 6.4 (95% CI: 3.2-12.7, p < 0.001). Shorter maternal height, UtA-PI ≥ 95th percentile, and low PAPP-A were identified as significant independent risk factors associated with SGA and SGA combined with PTB. The best LR model was obtained for the composite outcome SGA < 3rd percentile and PTB < 32 weeks, with an AUC of 0.834, a sensitivity rate of 77%, and a false positive rate of 17%., Conclusion: The majority of pregnancies at risk for SGA combined with prematurity can be detected in the first trimester. However, larger datasets are necessary to develop robust predictive models., Competing Interests: Declarations. Conflicts of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethical approval: The present study was sought and granted approval by the Local Ethical Committees of Nova Medical School-Universidade Nova de Lisboa (No. 81/2020/CEFCM) and CHULC (reference number 950/2020). Both retrospective analyses before 2020 and prospective inclusions after 2020 were approved by the ethical committees, according to institutional policies and national laws. Consent to participate and for publication: Verbal informed consent was obtained from all subjects for participation and publication of data collection and obstetric outcomes in this cohort. Written consent was not sought for the present study before 2020 due to its retrospective nature and anonymous data collection. After 2020, written consent was obtained from all subjects for participation and publication. Declaration of generative AI and AI-assisted technologies in the writing process: During the preparation of this work, the authors used ChatGTP 3.5 only to improve language and readability. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the publication’s content., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The relationship between maternal thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase antibody (TPOAb) status and hypertensive disorders of pregnancy (HDP) remains uncertain. Methods: This was a prospective cohort study based on the China Birth Cohort Study (CBCS). 36,256 women were included at 6 to 13 +6 gestation from February 2018 to December 2020. Generalized linear mixed models were used to investigate the association between thyroid function and HDP/BP. We further performed multiple subgroup analyses to test the robustness of this association. Results: The final study population was 25,608, and the overall incidence of HDP was 8.0%. After adjusting for maternal age, pre-pregnancy BMI, education, household annual income, smoking status, conception method and parity, the odds of HDP increased by 3.0% with a 1-unit increase in TSH (OR 1.03, 95% CI 1.04-1.06). Maternal TSH and TPOAb positivity were associated with a higher risk of preeclampsia or eclampsia but not gestational hypertension (TSH: OR 1.04, 95% CI 1.01-1.07; TPOAb positivity: OR 1.30, 95% CI 1.09-1.56). TSH and TPOAb positivity were significantly and positively associated with systolic pressure (TSH: β 0.02, 95% CI 0.07-0.26; TPOAb positivity: β 0.02, 95% CI 0.12-0.98) and diastolic pressure (TSH: β 0.02, 95% CI 0.02-0.17; TPOAb positivity: β 0.02, 95% CI 0.06-0.75). Subgroup analyses suggested that the association between TSH and diastolic pressure was stronger in those with BMI ≥ 25 kg/m 2 ( P = 0.014). Conclusions: Our founds suggest that high TSH and TPOAb positivity in the first trimester are associated with an increased risk of preeclampsia or eclampsia., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Preeclampsia is one of the leading causes of maternal morbidity, with consequences during and after pregnancy. Because of its diverse clinical presentation, preeclampsia is an adverse pregnancy outcome that is uniquely challenging to predict and manage. In this paper, we developed racial bias-free machine learning models that predict the onset of preeclampsia with severe features or eclampsia at discrete time points in a nulliparous pregnant study cohort. To focus on those most at risk, we selected probands with severe PE (sPE). Those with mild preeclampsia, superimposed preeclampsia, and new onset hypertension were excluded.The prospective study cohort to which we applied machine learning is the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) study, which contains information from eight clinical sites across the US. Maternal serum samples were collected for 1,857 individuals between the first and second trimesters. These patients with serum samples collected are selected as the final cohort.Our prediction models achieved an AUROC of 0.72 (95% CI, 0.69-0.76), 0.75 (95% CI, 0.71-0.79), and 0.77 (95% CI, 0.74-0.80), respectively, for the three visits. Our initial models were biased toward non-Hispanic black participants with a high predictive equality ratio of 1.31. We corrected this bias and reduced this ratio to 1.14. This lowers the rate of false positives in our predictive model for the non-Hispanic black participants. The exact cause of the bias is still under investigation, but previous studies have recognized PLGF as a potential bias-inducing factor. However, since our model includes various factors that exhibit a positive correlation with PLGF, such as blood pressure measurements and BMI, we have employed an algorithmic approach to disentangle this bias from the model.The top features of our built model stress the importance of using several tests, particularly for biomarkers (BMI and blood pressure measurements) and ultrasound measurements. Placental analytes (PLGF and Endoglin) were strong predictors for screening for the early onset of preeclampsia with severe features in the first two trimesters., Competing Interests: Declarations. Ethics approval and consent to participate: Human subjects approval for this study, titled "SCH: Prediction of Preterm Birth in Nulliparous Women", was obtained following review by Columbia University Human Subjects Institutional Review Board, and the City University of New York CUNY Institutional Review Board. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Early identification of gestational diabetes mellitus is essential for improving maternal and neonatal outcomes. While risk factors such as advanced maternal age, elevated pre-pregnancy body mass index, multiparity, and a history of gestational diabetes have been recognized, the role of serum biomarkers remains uncertain. This study explores the predictive value of early-pregnancy laboratory findings in conjunction with maternal demographic and clinical characteristics for gestational diabetes mellitus., Methods: Early-pregnancy data from the first pregnancy visits at 6-12 weeks of gestation from women in the Mothers and Children's Health cohort were collected. Comprehensive maternal demographic data (e.g., age and body mass index) and obstetrics history (e.g., gravidity, parity, miscarriage, intrauterine growth retardation, gestational diabetes mellitus, and preeclampsia) were recorded. Maternal blood samples were analyzed for complete blood count and biochemistry parameters. Gestational diabetes mellitus was diagnosed based on 75-g oral glucose tolerance test results between 24 and 28 weeks of gestation, following the International Association of Diabetes and Pregnancy Study Groups criteria. Multivariate logistic regression analysis assessed the predictive capacity of various variables. Receiver operating curve analysis was conducted to identify optimal predictive cut-offs for continuous variables., Results: 1,565 pregnant women with a mean age of 32.6 ± 5.7 years, mean body mass index of 25.5 ± 4.9 kg/m², mean gravidity of 1.1 ± 1.1, and mean parity of 0.8 ± 0.8 were included. 297 pregnancies (19.0%) were complicated by gestational diabetes mellitus. In the multivariate analysis, higher maternal age (p < 0.001, odds ratio = 1.076 [1.035-1.118]), a history of gestational diabetes mellitus (p < 0.001, odds ratio = 3.007 [1.787-5.060]) and preeclampsia (p = 0.007, odds ratio = 2.710 [1.310-5.604]), and elevated early-pregnancy fasting blood sugar (p < 0.001, odds ratio = 1.062 [1.042-1.083]) emerged as independent predictors of gestational diabetes mellitus. Moreover, the receiver operating curve yielded an optimal cut-off of 89.5 mg/dL for early-pregnancy fasting blood sugar in predicting gestational diabetes mellitus., Conclusions: Our findings demonstrated that, in addition to established risk factors, a history of preeclampsia and elevated early-pregnancy fasting blood glucose are independent predictors of gestational diabetes mellitus. Therefore, close monitoring of pregnant women with these risk factors in early pregnancy is warranted to facilitate timely diagnostic and therapeutic interventions, reducing the burden of gestational diabetes., Trial Registration: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: The MATCH cohort study protocol received approval from the institutional review board and ethical committee of the Tehran University of Medical Sciences on October 12, 2019, under reference code IR.TUMS.MEDICINE.REC.1398.576 (available at https://ethics.research.ac.ir/PortalCommittee.php?code=IR.TUMS.MEDICINE.REC ). Also, prior to enrollment, participants received explicit verbal and written explanations of the study, and informed consent was obtained for both participation and the anonymous publication of their data. Participants were allowed to withdraw from the study at any stage without affecting their routine prenatal or postnatal care. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: The aim of this study was to evaluate the serum hCG level in the differential diagnosis between non-molar miscarriage and complete hydatidiform mole in<11 weeks gestation., Methods: This was a retrospective collaborative cohort study. This study included women with gestational age<11 weeks, with ultrasound evidence of failed pregnancy and available serum hCG pre-uterine evacuation, divided into two groups: the non-molar miscarriage group and the complete hydatidiform mole group. Serum hCG levels were compared according to gestational age. Statistical analysis used a nonparametric test with a 5% significance level (p<0.05)., Results: In total, 416 patients were included, out of which 79 were included in the non-molar miscarriage group and 337 in the complete hydatidiform mole group. The calculated power of the sample was more than 80%. Data analysis showed that the 75th quartile of the median in the non-molar miscarriage group was always lower than the 25th quartile of the median in the complete hydatidiform mole group [9,721 mUI/mL/16,435 mUI/mL (6-7 weeks), 20,229 mUI/mL/64,911 mUI/mL (8-9 weeks), and 29,633 mUI/mL/126,278 mUI/mL (10-11 weeks), respectively; p<0.001]., Conclusion: Facing failed pregnancies, hCG>16,435 mUI/mL at 6-7 weeks, hCG>64,911 mUI/mL at 8-9 weeks, and hCG >126,278 mUI/mL at 10-11 weeks were most prevalent on complete hydatidiform mole diagnosis. On the contrary, hCG<30,000 mUI/mL at 10-11 weeks was most prevalent in non-molar miscarriage diagnosis.

Per- and polyfluoroalkyl substances (PFAS) have been detected in the blood of humans and animals worldwide. Exposure to some PFAS are associated with multiple adverse pregnancy outcomes. Existing literature has identified a strong association with PFAS exposure and metabolic dysfunction in humans, including modification of lipid metabolism. Using a subset of the Michigan Mother-Infant Pairs cohort (n = 95), this study investigated associations between first trimester plasma levels of PFAS and maternal lipids and metabolites in the first trimester (T1), at the time of delivery (T3), and in the infant cord blood (CB) using untargeted shotgun lipidomics and metabolomics. Identifying PFAS-induced alterations in the maternal lipid- or metabolome at specific timepoints may help elucidate windows of susceptibility to adverse pregnancy outcomes. Out of 9 PFAS measured, 7 were detected in at least 20% of samples and were used for further analyses. PFOS and PFHxS were measured at the highest concentrations with medians of 5.76 ng/mL and 3.33 ng/mL, respectively. PFOA, PFNA, and PFDA had lower measured values with medians of <1.2 ng/mL. PFHxS concentrations were positively associated with monounsaturated sphingomyelins (SMs) in T1 maternal plasma in adjusted models, determined by an adjusted p-value (q) < 0.1. PFHxS was positively associated with saturated and polyunsaturated SMs and inversely associated with saturated diacylglycerols in T1. Following metabolite-specific analysis, two mono-unsaturated diacylglycerols with carbon chain lengths of 32 and 35 were inversely associated with PFHxS in T1. In T3, only the association between PFHxS and SMs remained, but was attenuated. In addition, PFDA was associated with an increase in polyunsaturated plasmenyl-phosphatidylethanolamines in T3. No associations were identified between PFAS and infant cord blood lipids. Continued research into PFAS associated disruptions in lipid metabolism at sensitive stages of gestation may provide insight into the mechanisms that lead to adverse birth and pregnancy outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Preeclampsia (PE) is a pregnancy complication marked by high blood pressure, posing risk to maternal and fetal health. "Genomic imprinting", an epigenetic phenomenon regulated by DNA methylation at Differently Methylated Regions (DMR's), influences placental development. Research on circulating extracellular vesicles (EVs) in PE suggests them as potential source for early biomarkers, but methylation status of EV-DNA in Preeclampsia is not reported yet., Methods: This study examines the methylation and expression profile of imprinted genes - PEG10, PEG3, MEST, and DLK1 in circulating EVs of 1 st and 3 rd trimester control and early onset preeclampsia (EOPE) pregnant women (n = 15) using pyrosequencing and qRT-PCR respectively., Results: In 1 st trimester, PEG3 was significantly hypermethylated, whereas no significant methylation changes were noted in PEG10 and MEST in EOPE. In 3 rd trimester, significant hypomethylation in PEG10, PEG3 and IGDMR was observed whereas significant hypermethyaltion noted in MEST. mRNA expression of PEG10, PEG3 and DLK1 was not affected in circulating EVs of 1 st trimester EOPE. However, in 3 rd trimester significant increased expression in PEG10, PEG3 and DLK1 noted. MEST expression was reduced in 3 rd trimester EOPE. No correlation was observed between average DNA methylation and gene expression in PEG10 and PEG3 in 1 st trimester. However, in 3 rd trimester, significant negative correlation was noted in PEG10 (r = -0.426, p = 0.04), PEG3 (r = -0.496, p = 0.01), MEST (r = -0.398, p = 0.03) and DLK1 (r = -0.403, p = 0.03)., Discussion: The results of our study strengthen the potential of circulating EVs from maternal serum as non-invasive indicators of placental pathophysiology, including preeclampsia., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: To explore the relationship between maternal glycaemic control and fetal abdominal circumference in pregnancies complicated by T1D., Methods: This is a retrospective cohort study of 81 pregnant women with T1D using CGM. Inclusion criteria were T1D, CGM use, ≥2 in-house ultrasounds, and the birth of a live singleton neonate between 1st December 2019 and 1st December 2022. Linear regression analysis was used to assess the cross-sectional relationships between estimated fetal abdominal circumference (AC) on ultrasound and time in range (TIR) at matched time-points in the third trimester of pregnancy. Linear regression analysis was also used to examine whether first trimester TIR and HbA1c predicts third trimester fetal AC., Results: At baseline, the mean ± standard deviation (SD) of the first trimester HbA1c was 7.0 ± 1.4% and mean ± SD total daily dose (TDD) insulin was 46.6 ± 21.0 units. The mean ± SD birthweight was 3367.0 ± 861.3 grams. There was no cross-sectional relationship between TIR and fetal AC at 28-, 32- or 36-week' gestation. The results of the regression analysis indicate a significant relationship between first trimester TIR (independent predictor) and fetal AC (dependent variable) at 32- and 36-weeks' gestation while controlling for maternal age, BMI, pump use, and TDD insulin (Adj β= -0.42, 95%CI -0.80 to -0.03 and Adj β = - 0.57, 95%CI -1.02 to -0.12 at 32- and 36-weeks respectively). Although there was a significant relationship between first trimester HbA1c and fetal AC at 32-weeks' gestation ( β =  3.81, 95%CI 0.29 to 7.33), the relationship was not significant after adjustment for confounders., Conclusions: There was no cross-sectional relationship between TIR and fetal AC in the third trimester of pregnancy but first trimester TIR did predict fetal AC in late pregnancy.

Objective: Preeclampsia (PE) is a pregnancy-specific hypertensive disorder. Late-onset (Lo)-PE can cause serious complications in both the mother and child. This study aimed to explore biomarkers for elucidating the mechanisms underlying Lo-PE, via a metabolomic analysis of first-trimester maternal serum., Methods: This study was conducted at Fukushima Regional Center as an adjunct to Japan Environment and Children Study and included 12 patients with Lo-PE matched to 12 women with healthy pregnancies. Capillary electrophoresis-mass spectrometry-based quantitative analyses of charged metabolites were performed on first-trimester maternal serum samples., Results: Overall, 183 charged metabolites were identified. The peak area of glucosamine was significantly higher for the first-trimester sera of patients with Lo-PE than that for controls. Conversely, the peak area of serotonin was significantly decreased in the sera of patients with Lo-PE., Conclusions: During early pregnancy, glucosamine and serotonin levels in maternal serum may serve as early biomarkers for Lo-PE. As part of preconception care, pre-pregnancy dietary habits and mental health could potentially prevent Lo-PE onset.

Objective: To identify risk factors contributing to the development of postpartum hypothyroidism in women newly diagnosed with subclinical hypothyroidism (SCH) during the first trimester of pregnancy (T1). Additionally, this study aimed to explore the impact of thyroid peroxidase antibody (TPOAb) titers trajectories throughout pregnancy and postpartum., Methods: Thyroid hormone levels and thyroid autoantibody titers were collected from T1 to the 12 th month postpartum. Logistic regression analysis was employed to identify independent risk factors for hypothyroidism at the 12 th month postpartum and to develop a prediction model. Model performance was assessed through discrimination, calibration, and clinical applicability, with internal validation using the bootstrap resampling method. Growth Mixture Modeling was applied to delineate the trajectory of TPOAb titers during pregnancy and postpartum, and logistic regression analysis was conducted to investigate the influence of these trajectories on the occurrence of postpartum hypothyroidism., Results: At the 12 th month postpartum, hypothyroidism was either newly diagnosed or persisted in 76 of 209 cases (36.36%). Several significant risk factors for postpartum hypothyroidism were identified, including multiparity, positive TPOAb in T1, positive TPOAb and thyroglobulin antibody in T1, serum thyroid-stimulating hormone levels at SCH diagnosis in T1, and the final dose of levothyroxine in the third trimester. A prediction model was constructed and presented with a nomogram. Furthermore, a higher trajectory of serum TPOAb titer during pregnancy and postpartum emerged as a predictive factor for hypothyroidism at the 12 th month postpartum., Conclusion: Women with elevated TPOAb titers during pregnancy and postpartum necessitate ongoing and vigilant monitoring of thyroid function, even after childbirth., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethics approval: The study involving human participants was reviewed and approved by Ethics Committees of the Second Affiliated Hospital of Chongqing Medical University (2023 Research Project Ethics Review No. 25). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements. Consent to publish: All authors approved the final manuscript and the submission to this journal., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Studies have shown that members of the salusin family regulate the migration and proliferation of arterial smooth muscle cells and increase the tendency to atherosclerosis through fibrosis and calcification in the vascular wall. However, the effect of salusins on the uterine artery has not yet been investigated. This study was conducted to investigate whether serum salusin alpha and beta concentrations in the first trimester are associated with diastolic notching in uterine artery Doppler., Methods: This non-interventional cohort study was conducted on 88 pregnant women, 44 of whom had diastolic notching on unilateral or bilateral uterine artery Doppler, and 44 of whom did not have diastolic notching on uterine artery Doppler. The uterine artery notch positive and negative groups were compared in terms of serum salusin alpha and beta concentrations., Results: The two groups were similar in terms of demographic characteristics ( p  < 0.05). The median salusin alpha concentration was found to be 689.4 pg/ml in the uterine artery notch positive group, while it was 734.6 pg/ml in the uterine artery notch negative group ( p  = 0.608). The median salusin beta concentration was found to be 674.5 pg/ml in the uterine artery notch positive group, while it was 693.8 pg/ml in the uterine artery notch negative group ( p  = 0.453).Participants were regrouped into normal and high uterine artery resistance and compared in terms of serum salusin alpha and beta concentrations. The median salusin alpha concentration was found to be 994.5 pg/ml in the high uterine artery PI group, while it was 685.2 pg/ml in the normal uterine artery PI group ( p  = 0.698). The median salusin beta concentration was found to be 1,100.8 pg/ml in the high uterine artery PI group, while it was 669.1 pg/ml in the normal uterine artery PI group ( p  = 0.584)., Conclusion: Although the sample size was too small to draw a definitive conclusion, our results indicate that uterine artery diastolic notching or increased resistance in the uterine artery does not appear to be associated with serum salusin alpha or beta concentrations.

Objective: To investigate the association between thyroid peroxidase antibody (TPOAb) positivity in the first trimester and maternal metabolic syndrome in pregnancy., Methods: The study retrospectively reviewed the medical records for 787 pregnant women. Serum-free thyroid hormone, thyroid stimulating hormone, and TPOAb levels were measured in early pregnancy (<13 weeks gestation). Baseline demographics, clinical characteristics, thyroid function, and pregnancy outcomes were compared between women who were TPOAb positive or TPOAb negative in the first trimester. Associations between TPOAb positivity in the first trimester and the occurrence of gestational diabetes mellitus, hypertensive disorders complicating pregnancy (HDCP), maternal metabolic syndrome in pregnancy, and adverse pregnancy outcomes were explored., Results: Data for 787 women with a singleton pregnancy were included in the analyses. In women who were TPOAb positive compared to TPOAb negative in the first trimester, baseline HDL-C was significantly lower (1.51 [1.33, 1.81] vs. 1.62 [1.40, 1.87], p =  0.028), and there was a significantly higher incidence of HDCP (15.8% vs. 6%, p  < 0.0001), maternal metabolic syndrome in pregnancy (18.8% vs 6.4%, p  < 0.0001) or preeclampsia (7% vs, 2.5%, p  = 0.024). There was a significant nonlinear association between TPOAb levels in the first trimester and the incidence of HDCP or maternal metabolic syndrome in pregnancy (both p  < 0.001). The logit of the probability of having HDCP or maternal metabolic syndrome in pregnancy increased rapidly at TPOAb (log 10 ) ≤ 1.5 (TPOAb (log 10 ) = 1.07 as reference). After adjusting for confounders (maternal age, pre-pregnancy BMI, gravidity, parity and history of adverse events during pregnancy), there was a significantly higher risk of HDCP (odds ratio [OR], 3.029; 95% confidence interval [CI], 1.586, 5.622, p  = 0.001), maternal metabolic syndrome in pregnancy (OR, 2.841; 95% CI, 1.473-5.260, p  = 0.001), or preeclampsia (OR 3.315, 95% CI 1.305-7.788, p  = 0.008) in women who were TPOAb positive compared to TPOAb negative in the first trimester., Conclusion: TPOAb positivity in the first trimester may increase the risk of HDCP, maternal metabolic syndrome in pregnancy, and preeclampsia, emphasizing the need for universal screening for thyroid disorders and better diagnostic criteria and management strategies for metabolic disorders during pregnancy.

Background: Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy, which increases the risk of other pregnant complications and adverse perinatal outcomes. Thyroid dysfunction is closely with the risk of diabetes mellitus. However, the relationship between euthyroid function in early pregnancy and GDM is still controversial., Aims: This study was to find the relationship between thyroid function within normal range during early pregnancy as well as glucose and lipids metabolisms as well as the risk of subsequent GDM., Methods: A total of 1486 pregnant women were included in this prospective double-center cohort study. Free thyroxine (FT4), thyroid stimulating hormone (TSH) and antithyroid peroxidase antibodies (TPOAb) were tested during 6-12 weeks of gestation and oral glucose tolerance test (OGTT) was conducted during 24-28 weeks to screen GDM. Relative risks (RR) with 95% confidence intervals (CI) for subsequent risk of GDM by thyroid function quartiles were assessed adjusting for major risk factors., Results: The incidence of GDM was 23.0% (342/1486). TSH, FT4 and the percentage of positive TPOAb were no significant difference between women with and without GDM, but FT4/TSH ratio was significantly higher in GDM group compared with NGT group [6.97(0.84,10.61) vs. 4.88(0.66,12.44), P =0.025)]. The linear trends of TC, TG, HDL-C, LDL-C, fasting glucose in the first trimester, insulin, C-peptide, HOMA-IR, fasting glucose during OGTT and incidence of GDM according to FT4/TSH ratio were all statistically significant. Further analysis based on fetal sex presented only the third quartile of FT4/TSH ratio in women carrying male fetus was associated with higher incidence of GDM statistically significant [RR (95% CI), 1.917 (1.143,3.216)], rather than in women carrying female fetus., Conclusions: Thyroid function even in normal range is closely related to glucose and lipids metabolisms during the first trimester. Unappropriated FT4/TSH ratio in the first trimester is an independent risk factor of GDM in women carrying male fetus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Zhang, Qiao, Duo, Xu, Zhang, Chen, Nie, Sun, Yang, Wang, Lu, Sun, Fu, Dong, Yuan and Zhao.)

Background: Despite the global standardization of hemoglobin (Hb) testing in early pregnancy, the impact of first trimester Hb concentrations on pregnancy outcomes remains inadequately understood. Also, the early pregnancy Hb concentrations have not been well documented in Western China. Therefore, this study aimed to assess the Hb concentrations during early pregnancy and their associations with adverse pregnancy outcomes in Western China., Methods: This cross-sectional study used data from the Chengdu Maternal and Child Health Information System for pregnant women who delivered between January 1, 2019, and December 31, 2023. A total of 454,815 Chinese females aged 15 to 49 years with available first trimester Hb data, including those with singleton or multiple gestations, were included in the analysis. Multivariable logistic regression models were performed to estimate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between Hb categories and adverse pregnancy outcomes., Results: The average first trimester Hb concentration was 126.0 (SD 10.5) g/L, with 5.8% of pregnant women experiencing anemia during early pregnancy. Multivariable logistic regression analyses revealed significantly increased odds of developing gestational diabetes mellitus (GDM) and gestational hypertensive disorders (GHD) across increasing Hb concentration categories. Compared to Hb concentrations of 110-119 g/L, Hb ≥ 140 g/L was associated with elevated risk of GDM (aOR: 1.57, 95% CI: 1.52, 1.62) and GHD (aOR: 1.87, 95% CI: 1.79, 1.96). Moreover, both Hb ≤ 99 g/L (aOR: 1.15, 95% CI: 1.03, 1.29) and Hb ≥ 140 g/L (aOR: 1.20, 95% CI: 1.13, 1.26) were associated with higher odds of preterm birth compared to Hb concentrations of 110-119 g/L. In addition, the restricted cubic spline demonstrated a U-shaped relationship for cesarean delivery, low birthweight and small for gestational age (p < 0.001). However, no significant associations were found between first trimester Hb concentrations and the odds of stillbirth, Apgar score < 7 at 5 min, or Apgar score < 7 at 10 min (p > 0.05)., Conclusions: Our research findings suggest associations between first trimester Hb concentrations and various adverse pregnancy outcomes. We recommend interventions for early pregnancy anemia, particularly moderate to severe cases, and emphasize monitoring females with high Hb concentrations to reduce adverse outcomes., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of Chengdu Women’s and Children’s Central Hospital (approval number: 202285). Informed consent was waived because of the retrospective study design, and the data analyses used data containing no personally identifiable information. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Prenatal exposure to heavy metals such as Lead (Pb), arsenic (As), cadmium (Cd), and selenium (Se) is associated with various adverse pregnancy outcomes. This study examines the association between early pregnancy maternal blood levels of these metals and adverse pregnancy outcomes, while also addressing the differences between low-risk and high-risk groups based on having a history of preterm birth (PTB). This prospective cohort study recruited parous women during first trimester, categorized into low-risk and high-risk groups. Participants completed a questionnaire, and heavy metal levels were measured in blood samples. Pregnancy outcomes including PTB, low birth weight (LBW), gestational age at delivery, birth weight and head circumference were recorded following delivery. Multivariable analyses were conducted to evaluate the independent associations between heavy metal levels and pregnancy outcomes, while adjusting for maternal age, BMI, employment, smoking, fertility treatments and education. Among 404 participants, the mean (± SD) levels were Pb: 3.12 ± 1.82 µg/L, As: 0.41 ± 0.4 µg/L, Cd: 0.26 ± 0.34 µg/L, and Se: 119.84 ± 21.05 µg/L. Significant differences in Pb, Se, Cd and As levels were observed between the low-risk and high-risk groups, with higher levels in the low-risk group. However, no significant associations were found between heavy metal levels and any of the study outcomes in either univariable comparison or multivariable models. These findings highlight the need for further research to understand the potential impact of these metals on pregnancy, considering population-specific factors and exposure timing., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics declaration The study protocol was approved by the institutional review board (Soroka University Medical Center IRB committee, #0390-20-SOR). The study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments (Helsinki Declaration 1975, revision 2013). All participants gave signed informed consent at recruitment., (© 2024. The Author(s).)

Objective (s): Circulating angiogenic factors are used for prediction of placenta-related complications, but their associations with first-trimester placental development is unknown. This study investigates associations between maternal angiogenic factors and utero-placental vascular volume (uPVV) and utero-placental vascular skeleton (uPVS) as novel imaging markers of volumetric and morphologic (branching) development of the first-trimester utero-placental vasculature., Methods: In 185 ongoing pregnancies from the VIRTUAL Placenta study, a subcohort of the ongoing prospective Rotterdam Periconception cohort, three-dimensional power Doppler ultrasounds of the placenta were obtained at 7-9-11 weeks gestational age (GA). The uPVV was measured as a parameter of volumetric development and reported the vascular quantity in cm 3 . The uPVS was generated as a parameter of morphologic (branching) development and reported the number of end-, bifurcation- crossing- or vessel points and total vascular length. At 11 weeks GA, maternal serum biomarkers suggested to reflect placental (vascular) development were assessed: placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). sFlt-1/PlGF and sEng/PlGF ratios were calculated. Multivariable linear regression with adjustments was used to estimate associations between serum biomarkers and uPVV and uPVS trajectories., Results: Serum PlGF was positively associated with uPVV and uPVS development (uPVV: β = 0.39, 95% CI = 0.15;0.64; bifurcation points: β = 4.64, 95% CI = 0.04;9.25; crossing points: β = 4.01, 95% CI = 0.65;7.37; total vascular length: β = 13.33, 95% CI = 3.09;23.58, all p-values < 0.05). sEng/PlGF ratio was negatively associated with uPVV and uPVS development. We observed no associations between sFlt-1, sEng or sFlt-1/PlGF ratio and uPVV and uPVS development., Conclusion(s): Higher first-trimester maternal serum PlGF concentration is associated with increased first-trimester utero-placental vascular development as reflected by uPVV and uPVS. Clinical trial registration number Dutch Trial Register NTR6854., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical approval The authors report no conflicts of interest. This research was conducted in accordance with the ethical principles for medical research set out in the Declaration of Helsinki and was approved by the Institutional Review Board of the Erasmus Medical Centre on 2 June 2015 (MEC 2015–494).This study was registered at the Dutch Trial Register: NTR6854., (© 2024. The Author(s).)

Objective: Impaired fasting glucose is a prediabetic condition defined as glucose levels of 100-125 mg/dL and is considered a risk factor for type 2 diabetes. However, this definition does not confer to pregnancy. The significance of first-trimester fasting glucose and future progression to diabetes is not well defined. Therefore, we aimed to evaluate the progression to type 2 diabetes according to first- trimester fasting plasma glucose levels, as compared with gestational diabetes, a well-established risk factor for diabetes, in up to 5-year follow-up postpartum., Methods: A retrospective analysis of 69 001 parturients, evaluating fasting plasma glucose levels measured during the first trimester. The primary outcome was the incidence of type 2 diabetes within 5 years post-delivery. Fasting plasma glucose levels were categorized in 10 mg/dL increments. Receiver operating characteristic-area under the curve (ROC-AUC) statistics and the Youden index were employed to identify the optimal fasting plasma glucose cutoff for progression to type 2 diabetes. Survival analysis was applied to calculate the adjusted hazard ratios (aHRs) for type 2 diabetes progression with further stratification to maternal obesity status., Results: The identified fasting plasma glucose cutoff for progression to type 2 diabetes was 86.5 mg/dL. This cut-off demonstrated superior performance compared with gestational diabetes diagnosis. Stratification by maternal obesity revealed enhanced predictive capabilities for type 2 diabetes, particularly among patients without obesity., Conclusions: Increased first-trimester fasting plasma glucose levels are associated with progression to type 2 diabetes, at least as gestational diabetes. For patients without obesity, first-trimester fasting plasma glucose has a more pronounced impact on progression to diabetes., (© 2024 International Federation of Gynecology and Obstetrics.)

Objective: This study evaluates differences in first and second-trimester maternal serum biomarkers for aneuploidy screening among women with placenta accreta spectrum (PAS) disorders, placenta previa, and those with normal placentation., Data Sources: A systematic review of 5 major databases up to April 2023 was conducted. Included were comparative studies analyzing mean biomarker levels in multiples of the median (MoM) among pregnant women with PAS, placenta previa, and uncomplicated pregnancies., Study Selection: Both observational studies and randomized controlled trials were included in this meta-analysis., Data Extraction and Data Synthesis: Analysis of 8 retrospective studies involving 1886 participants showed significant variances in biomarker levels. In the first trimester, pregnancy-associated plasma protein-A levels were notably higher in the PAS group compared to the placenta previa group (731 patients, mean difference (MD) 0.48 MoM; 95% CI 0.23 to 0.73, P = 0.0001). Also, β-human chorionic gonadotropin levels were elevated in the placenta previa group compared to those with normal attachment (362 patients, MD 0.27 MoM; 95% CI 0.17 to 0.38, P < 0.00001). In the second trimester, alpha fetoprotein and human chorionic gonadotropin levels were significantly increased in PAS patients compared to the placenta previa and normal groups, indicating potential markers for PAS., Conclusions: Significant differences in early pregnancy biomarker levels among women with PAS, placenta previa, and normal placentation were identified. These findings suggest potential for early screening, but further large-scale studies are essential for validation. This study underscores the need for improved screening methods for placental disorders, potentially aiding in early diagnosis and management strategies., (Copyright © 2024 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Gestational diabetes mellitus (GDM) is the first spontaneous hyperglycemia during pregnancy. Early diagnosis and intervention are important for the management of the disease. This study compared and analyzed the proteins of total plasma exosomes (T-EXO) and placental-derived exosomes (PLAP-EXO) in pregnant women who subsequently developed GDM (12-16 weeks), GDM patients (24-28 weeks) and their corresponding controls to investigate the pathogenesis and biomarkers of GDM associated with exosomes. The exosomal proteins were extracted and studied by proteomics approach, then bioinformatics analysis was applied to the differentially expressed proteins (DEPs) between the groups. At 12-16 and 24-28 weeks of gestation, 36 and 21 DEPs were identified in T-EXO, while 34 and 20 DEPs were identified in PLAP-EXO between GDM and controls, respectively. These proteins are mainly involved in complement pathways, immunity, inflammation, coagulation and other pathways, most of them have been previously reported as blood or exosomal proteins associated with GDM. The findings suggest that the development of GDM is a progressive process and that early changes promote the development of the disease. Maternal and placental factors play a key role in the pathogenesis of GDM. These proteins especially Hub proteins have the potential to become predictive and diagnostic biomarkers for GDM., (© 2024. The Author(s).)

The association between early pregnancy ultrasound parameters and reproductive hormone levels was investigated through a case-control study. Participants for this retrospective study were recruited from obstetrics and gynecology departments across multiple tertiary care centers over 2 years. Inclusion criteria for the case group included pregnant women in their first trimester with detailed ultrasound data, while the control group comprised nonpregnant women without hormonal disorders. A sample size of 850 was estimated to provide sufficient power for detecting differences in hormone levels. Hormone levels were assayed using enzyme-linked immunosorbent assay, and statistical analysis was performed using Statistical Package for the Social Sciences 26.0. A total of 425 participants in each group were included after accounting for dropouts. For hCG, a strong positive correlation was observed with crown-rump length (R = 0.62, P < .001), gestational sac diameter (R = 0.59, P < .001), and a moderate correlation with yolk sac diameter (R = 0.40, P = .003). Progesterone levels exhibited moderate positive correlations with these ultrasound parameters, and estradiol levels demonstrated strong positive correlations. Conversely, follicle-stimulating hormone levels showed a moderate negative correlation with ultrasound measurements, while luteinizing hormone levels indicated a slight negative correlation. Prolactin levels were positively correlated with all ultrasound parameters in cases. The control group did not show any significant correlations between hormone levels and ultrasound parameters. The study concluded a significant association between early pregnancy ultrasound parameters and reproductive hormone levels in pregnant women, underscoring the potential of these hormones as biomarkers for pregnancy development., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Preeclampsia (PE) is a complex and multifaceted obstetric syndrome characterized by several distinct molecular subtypes. It complicates up to 5% of pregnancies and significantly contributes to maternal and newborn morbidity, thereby diminishing the long-term quality of life for affected women. Due to the widespread dissatisfaction with the effectiveness of existing approaches for assessing PE risk, there is a pressing need for ongoing research to identify newer, more accurate predictors. This study aimed to investigate early changes in the maternal serum proteome and associated signaling pathways. The levels of 125 maternal serum proteins at 11-13 weeks of gestation were quantified using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) with the BAK-125 kit. Ten serum proteins emerged as potential early markers for PE: Apolipoprotein M (APOM), Complement C1q subcomponent subunit B (C1QB), Lysozyme (LYZ), Prothrombin (F2), Albumin (ALB), Zinc-alpha-2-glycoprotein (AZGP1), Tenascin-X (TNXB), Alpha-1-antitrypsin (SERPINA1), Attractin (ATRN), and Apolipoprotein A-IV (APOA4). Notably, nine of these proteins have previously been associated with PE in prior research, underscoring the consistency and reliability of our findings. These proteins play key roles in critical molecular processes, including complement and coagulation cascades, platelet activation, and insulin-like growth factor pathways. To improve the early prediction of PE, a highly effective Support Vector Machine (SVM) model was developed, analyzing 19 maternal serum proteins from the first trimester. This model achieved an area under the curve (AUC) of 0.91, with 87% sensitivity and 95% specificity, and a hazard ratio (HR) of 13.5 (4.6-40.8) with p < 0.001. These findings demonstrate that serum protein-based SVM models possess significantly higher predictive power compared to the routine first-trimester screening test, highlighting their superior utility in the early detection and risk stratification of PE.

Background: Subclinical hypothyroidism (SCH) in pregnancy is associated with adverse foetomaternal outcomes. The literature is scarce with respect to maternal and perinatal outcomes in women with mild SCH (TSH levels between 2.5-4 mIU/L)., Objectives: The primary objective of the study was to compare the pregnancy outcome between SCH and euthyroid women. The secondary objectives were to find out the proportion of women with SCH having thyroid peroxidase antibodies (TPOAb) and to see the effect of TPOAb positivity on foetomaternal outcomes., Materials and Methods: A total of 178 pregnant women were recruited in the first trimester, and those with TSH between 0.1 and 2.4 mIU/L were considered as euthyroid and 2.5-4mIU/L were labelled as SCH. Women with SCH underwent testing for TPOAb. All women were followed until delivery, and foetomaternal outcomes were assessed., Results: Amongst SCH group, there was a significantly higher proportion of overweight and obese women (76/91 (83.51%) vs 59/87 (68%), p = 0.031). The neonatal intensive care unit (NICU) admission was higher with adjusted odds ratio of 3.24 (1.41-7.43) in women with SCH as compared to euthyroid women. Otherwise, there was no difference in foetomaternal outcomes between the two groups. The proportion of gestational diabetes mellitus, intrauterine growth retardation and still birth were higher in SCH women with TPOAb as compared to euthyroid. Amongst SCH women, the proportion of induced labour was lower (aOR:0.27 (0.08-0.93) whereas the proportion of stillbirth and low APGAR scores were higher in TPOAb-positive women with a statistically significant difference and adjusted odds ratio (aOR:20.18 (1.84-220.83)) and (aOR:4.77 (1.06-21.3)), respectively, when compared to TPOAb-negative women., Conclusion: There appears to be no difference in pregnancy outcomes between women with SCH and euthyroid women except higher NICU admission in SCH group. Future multi-centre large prospective studies are required to understand better about the pregnancy outcomes in these women., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Exposure to certain heavy metals has been demonstrated to be associated with a higher risk of preterm birth (PTB). However, studies focused on the effects of other metal mixtures were limited. A nested case‒control study enrolling 94 PTB cases and 282 controls was conducted. Metallic elements were detected in maternal plasma collected in the first trimester using inductively coupled plasma‒mass spectrometry. The effect of maternal exposure on the risk of PTB was investigated using logistic regression, least absolute shrinkage and selection operator, restricted cubic spline (RCS), quantile g computation (QGC) and Bayesian kernel machine regression (BKMR). Vanadium (V) and arsenic (As) were positively associated with PTB risk in the logistic model, and V remains positively associated in the multi-exposure logistic model. QGC analysis determined V (69.42%) and nickel (Ni) (70.30%) as the maximum positive and negative contributors to the PTB risk, respectively. BKMR models further demonstrated a positive relationship between the exposure levels of the mixtures and PTB risk, and V was identified as the most important independent variable among the elements. RCS analysis showed an inverted U-shape effect of V and gestational age, and plasma V more than 2.18 μg/L was considered a risk factor for shortened gestation length. Exposure to metallic elements mixtures consisting of V, As, cobalt, Ni, chromium and manganese in the first trimester was associated with an increased risk of PTB, and V was considered the most important factor in the mixtures in promoting the incidence of PTB., (© 2024 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Pregnant women are advised to take folic acid (FA) supplements before conception and during the first trimester of pregnancy. Many women continue FA supplementation throughout pregnancy, and concerns have been raised about associations between excessive FA intake and adverse maternal and child health outcomes. Unmetabolized folic acid (UMFA) is found in serum after high FA intakes and is proposed as a biomarker for excessive FA intake. We aimed to determine if removing FA from prenatal micronutrient supplements after 12 weeks of pregnancy reduces serum UMFA concentrations at 36 weeks gestation. In this double-blind, randomized controlled trial conducted in South Australia, 103 women with a singleton pregnancy were randomly assigned at 12-16 weeks gestation to take a micronutrient supplement containing no FA or 800 µg/day FA from enrollment until 36 weeks gestation. Ninety women (0 µg/day FA n = 46; 800 µg/day FA n = 44) completed the study. Mean, UMFA concentration was lower in the women randomized to the 0 µg/day group compared to the 800 µg/day FA group, 0.6 ± 0.7 and 1.4 ± 2.7 nmol/L, respectively. The adjusted mean difference (95% CI) in UMFA between the groups was [-0.85 (-1.62, -0.08) nmol/L, p = 0.03]. Maternal serum and red blood cell folate concentrations were lower in the 0 µg/day FA group than in the 800 µg/day group (median 23.2 vs. 49.3 and 1335 vs. 1914 nmol/L, respectively; p < 0.001). Removing FA at 12-16 weeks gestation from prenatal micronutrient supplements reduced the concentration of UMFA at 36 weeks gestation., (© 2024 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Objective: To evaluate the associations of plasma polybrominated diphenyl ether (PBDE) concentrations in early pregnancy with gestational weight gain (GWG)., Design: Prospective cohort study., Setting: US-based, multicentre cohort of pregnant women., Population: We used data from 2052 women without obesity and 397 women with obesity participating in the NICHD Fetal Growth Studies - Singleton Cohort, with first-trimester plasma PBDE concentrations and weight measurements throughout pregnancy., Methods: We applied generalised linear models and Bayesian kernel machine regression (BKMR) to evaluate both the individual and joint associations of PBDEs with measures of GWG, adjusting for potential confounders., Main Outcome Measures: Total GWG (kg), total and trimester-specific GWG velocities (kg/week), and GWG categories and trajectory groups., Results: Mean pre-pregnancy BMIs were 23.6 and 34.5 kg/m 2 for women without and with obesity, respectively. Among women without obesity, there were no associations of PBDEs with any GWG measure. Among women with obesity, one standard deviation increase in log-transformed PBDE 47 was associated with a 1.87 kg higher total GWG (95% CI 0.39-3.35) and a 0.05 kg/week higher total GWG velocity (95% CI 0.01-0.09). Similar associations were found for PBDE 47 in BKMR among women with obesity, and PBDE 47, 99 and 100 were associated with lower odds of being in the low GWG trajectory group., Conclusions: PBDEs were not associated with GWG among individuals without obesity. Among those with obesity, only PBDE 47 showed consistent positive associations with GWG measures across multiple statistical methods. Further research is needed to validate this association and explore potential mechanisms., (© 2024 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objective: To identify the relationship between white blood cell indices in missed miscarriage compared to ongoing pregnancy in the first trimester., Methods: The diagnostic accuracy study was conducted at the Department of Maternity, Al-Yarmouk Hospital, Baghdad, Iraq, from January to October 2021,and comprised healthy first-trimester pregnant women in group A and those with missed miscarriage after 7-13 weeks of gestation in group B. Ultrasound findings and the last menstrual period were noted for all the subjects. Total and differential leukocyte counts, neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio were compared between the groups. Data was analysed using SPSS 22., Results: Of the 167 women, 81(48.5%) were in group A and 86(51.5%) were in group B. Demographic and obstetrics data was not significantly different between the groups (p>0.05). Mean white blood cell, neutrophil and monocyte counts showed no significant difference between the groups (p>0.05), while lymphocyte count, neutrophil-tolymphocyte ratio and monocyte-to-lymphocyte ratio were significantly different between the groups (p<0.05). With respect to gestational age, neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio had a fair ability to predict missed miscarriage at various time points within the first trimester (p<0.05)., Conclusions: There was no significant correlation between WBC count and gestational age. Reduced MLR and NLR levels can be utilised to forecast miscarriages in a cost-effective manner.

Objective: The aim of this study was to evaluate the potential of immunonutritional markers, specifically the hemoglobin, albumin, lymphocyte, and platelet (HALP) score and the prognostic nutritional index (PNI), in predicting late-onset fetal growth restriction (LO-FGR) during the first trimester., Materials and Methods: This retrospective study was conducted at a tertiary care center between October 2022 and August 2023. The study included a total of 213 singleton pregnancies, with 99 women in the LO-FGR group and 114 in the healthy control group, matched by maternal age and gestational age at delivery. All blood samples were collected between 11 and 14 weeks of gestation (during the first-trimester screening test). We analyzed first-trimester laboratory parameters, specifically focusing on hemoglobin levels, white blood cells (WBCs), lymphocytes, platelets, and albumin levels. Afterwards, we calculated the HALP score and PNI, and then compared the values of both groups., Results: Both HALP score (3.58 ± 1.31 vs. 4.19 ± 1.8, p = 0.012) and PNI (36.75 ± 2.9 vs. 39.37 ± 3.96, p < 0.001) were significantly lower in the FGR group than in the control group. The HALP score cut-off value of < 3.43 in predicting FGR had a sensitivity of 62.3% and specificity of 54.5% (AUC = 0.600, 95% CI: 0.528-0.672, p = 0.012). The PNI cut-off value of < 37.9 in predicting FGR had a sensitivity of 65.8% and specificity of 62.9% (AUC = 0.707, 95% CI: 0.632-0.778, p < 0.001). While the HALP score was not a significant predictor of composite adverse neonatal outcomes in the FGR group, PNI showed a cut-off value of < 37.7 with a sensitivity of 60.9% and specificity of 59.7% (AUC = 0.657, 95% CI: 0.581-0.733, p < 0.001)., Conclusion: The HALP score and PNI are valuable prognostic tools for predicting the risk of FGR in the first trimester. Low PNI values are also associated with composite adverse neonatal outcomes in pregnancies complicated by FGR., (© 2024. The Author(s).)

Introduction: Preterm delivery (PTD) is the leading cause of death in children under 5 years of age. Cervical shortening detected by ultrasound can be used to predict PTD, but prediction is not perfect, and complementary diagnostic markers are needed. Recently, specific plasma microribonucleic acid (miRNAs) detected in early second trimester were shown to be associated with spontaneous PTD in high-risk women with a singleton pregnancy. The aim of this study was to explore to what extent these miRNAs are associated with spontaneous PTD and cervical length in a general population., Material and Methods: This study is a nested case-control study within the CERVIX study. The CERVIX study evaluated the ability of cervical length screening with transvaginal ultrasound to identify women at risk of PTD. In the present study, women who delivered spontaneously <34 weeks (n = 61) were compared with a control group of women who delivered at full term (39 + 0 to 40 + 6 gestational weeks, n = 205). Archived serum samples were analyzed with RT-qPCR for miRNA expression levels of let-7a-5p, miR-150-5p, miR-15b-5p, miR-185-5p, miR-191-5p, miR-19b-3p, miR-23a-3p, miR-374a-5p, and miR-93-5p. The mean relative expression was compared between the groups. Sub-analyses were performed for women delivering <32, <30, and <28 weeks vs the full-term group., Results: The analyzed miRNAs were not significantly differentially expressed in women delivering <34 weeks compared to those delivering at full term. MiR-191-5p and miR-93-5p were significantly overexpressed in women who delivered <32 weeks, and further increase in fold change was observed with decreasing gestational age at delivery. The level of miR-15b-5p was significantly higher in women delivering at <30 weeks compared to those delivering at full term., Conclusions: Our study shows that overexpression of miR-93-5p, miR-15b-5p, and miR-191-5p in serum at early gestation is associated with spontaneous PTD in a general population. Further research is needed to evaluate the potential of these miRNAs as future biomarkers for spontaneous PTD, as well as their pathophysiological role in spontaneous PTD., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Preterm birth (PTB) remains a significant public health concern, and prediction is an important objective, particularly in the early stages of pregnancy. Many studies have relied on cervical characteristics in the mid-trimester, with limited results. It is therefore crucial to identify novel biomarkers to enhance the ability to identify women at risk. The complement pathway is implicated in the process of placentation, and recent proteomics studies have highlighted the potential roles of some complement proteins in the pathophysiology of PTB. To determine the association between the occurrence of spontaneous preterm birth (sPTB) and the concentration of complement C3, factor B, and factor H in the blood of pregnant women during the first trimester. This prospective cohort study included women with singleton pregnancies, both with and without a history of sPTB, from two health institutions in Bucaramanga, Colombia. The outcome was sPTB before 37 weeks. A blood sample was obtained between 11 + 0 to 13 + 6 weeks. ELISA immunoassay was performed to quantify the levels of C3, factor B, and factor H. A total of 355 patients were analyzed, with a rate of sPTB of 7.6% (27/355). The median plasma concentration for C3, factor B, and factor H were 488.3 μg/mL, 352.6 μg/mL, and 413.2 μg/mL, respectively. The median concentration of factor H was found to be significantly lower in patients who delivered preterm compared to patients who delivered at term (382 μg/mL vs. 415 μg/mL; p = 0.034). This study identified a significant association between low first-trimester levels of factor H and sPTB before 37 weeks. These results provide relevant information about a new possible early biomarker for sPTB. However, the results must be confirmed in different settings, and the predictive value must be examined.

Exposure to mercury has been associated with adverse effects on pregnancy outcomes. However, there is limited literature on mercury exposure and pregnancy outcomes in Chinese pregnant women. Our study was to investigate the possible association between maternal mercury exposure and spontaneous preterm birth and birth weight. This study was a nested case-control study. The association between blood mercury concentration and both spontaneous preterm birth and birth weight was analyzed using conditional logistic regression and linear regression adjusted for the potential confounding factors, respectively. The dose-response relationship between mercury concentration and birth outcomes was estimated using restricted cubic spline regression. The mean concentration of mercury was 2.8 ± 2.2 µg/L. A positive relationship was observed between maternal blood mercury concentration and SPB when analyzed as a continuous variable. However, it was not found to be statistically significant (adjusted OR = 1.10, 95% CI = 0.95-1.26, P = 0.202). Moderate mercury exposure was associated with a higher risk of SPB (Q3 vs. Q1: crude OR = 2.50, 95% CI = 1.16-5.41, P = 0.02; adjusted OR = 3.49, 95% CI = 1.33-9.11, P = 0.011). After considering the combined effects of chemicals other than mercury exposure (including lead, selenium, and cadmium), the results remained consistent. There was no statistically significant association between blood mercury levels and birth weight (adjusted coefficient = 18.64, P-value = 0.075). There were no statistically significant dose-response associations between mercury concentration and birth outcomes (SPB: P = 0.076; birth weight: P = 0.885). Public health policies should focus on reducing environmental releases of mercury, improving food safety standards, and providing education to pregnant women about the risks of mercury exposure and preventive measures., (© 2024. The Author(s).)

Objective: The aim of this study was to investigate the role of systemic immune-inflammation index, neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and platelet-lymphocyte ratios calculated in the first trimester as inflammatory markers in predicting gestational diabetes mellitus diagnosis., Methods: This study was conducted retrospectively at a tertiary center between January 2020 and June 2023. A total of 111 pregnant women with gestational diabetes and 378 pregnant women in the control group were included in the study. Systemic immune-inflammation index, neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and platelet-lymphocyte ratios values were compared between the gestational diabetes mellitus group patients and the healthy group. Receiver operating characteristic analysis curve was used for predicting gestational diabetes mellitus using systemic immune-inflammation index and lymphocyte-monocyte ratio., Results: In pregnant women in the first trimester, systemic immune-inflammation index and lymphocyte-monocyte ratio values based on routine complete blood count parameters were found to be statistically significantly higher in gestational diabetes mellitus patients compared to healthy patients, while neutrophil-lymphocyte ratio and platelet-lymphocyte ratios values were found to be similar (p=0.033, p=0.005, p=0.211, and p=0.989). For predicting gestational diabetes mellitus, a cut-off value of 655.75 for systemic immune-inflammation index resulted in 80.2% sensitivity and 34.4% specificity, and a cut-off value of 3.62 for lymphocyte-monocyte ratio resulted in 56.8% sensitivity and 63.2% specificity, indicating good discriminatory ability., Conclusion: We believe that systemic immune-inflammation index and lymphocyte-monocyte ratio values measured in the first-trimester complete blood count parameters are effective in predicting gestational diabetes mellitus but are not effective in determining insulin requirement.

To assess how effective macrophage stimulating protein α-chain (MSP-α) combined with uterine artery Doppler is in predicting preeclampsia in singleton pregnancies during 11-13 +6  weeks of gestation. This prospective observational study included singleton pregnant women who attended antenatal care at King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University between December 2021 and April 2023, during 11-13 +6  weeks of gestation. Serum MSP-α levels were collected and uterine artery Doppler ultrasound was performed. Pregnancy outcomes were recorded, and the predictive values of these tests were determined to predict preeclampsia. A total of 365 patients, with 21 cases of preeclampsia (5.8%), were analyzed. Serum MSP-α levels were higher in pregnant women who developed preeclampsia than those who did not (899.7 ± 550.1 ng/ml vs 642.5 ± 466.1 ng/ml, p = 0.016). The mean pulsatility index of the uterine artery and the presence of diastolic notching were not significantly different between the groups. As a cut-off value for predicting preeclampsia, using serum MSP-α levels higher than 1.0 multiple of median for gestational age, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.4%, 50.3%, 8.1%, and 96.7%, respectively. Additionally, when abnormal serum MSP-α levels were combined with a uterine artery Doppler pulsatility index above the 95th percentile and bilateral notching as predictive values for preeclampsia, the sensitivity was 85.7%, specificity was 18.3%, PPV was 6.0%, and NPV was 95.5%. Serum MSP-α alone at 11-13 +6  weeks of gestation was effective in predicting preeclampsia. However, the use of serum MSP-α in combination with uterine artery Doppler increased sensitivity but reduced specificity for the prediction of preeclampsia., (© 2024. The Author(s).)

Background: It remains unclear which early gestational biomarkers can be used in predicting later development of gestational diabetes mellitus (GDM). We sought to identify the optimal combination of early gestational biomarkers in predicting GDM in machine learning (ML) models., Methods: This was a nested case-control study including 100 pairs of GDM and euglycemic (control) pregnancies in the Early Life Plan cohort in Shanghai, China. High sensitivity C reactive protein, sex hormone binding globulin, insulin-like growth factor I, IGF binding protein 2 (IGFBP-2), total and high molecular weight adiponectin and glycosylated fibronectin concentrations were measured in serum samples at 11-14 weeks of gestation. Routine first-trimester blood test biomarkers included fasting plasma glucose (FPG), serum lipids and thyroid hormones. Five ML models [stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, support vector machine and k-nearest neighbor] were employed to predict GDM. The study subjects were randomly split into two sets for model development (training set, n = 70 GDM/control pairs) and validation (testing set: n = 30 GDM/control pairs). Model performance was evaluated by the area under the curve (AUC) in receiver operating characteristics., Results: FPG and IGFBP-2 were consistently selected as predictors of GDM in all ML models. The random forest model including FPG and IGFBP-2 performed the best (AUC 0.80, accuracy 0.72, sensitivity 0.87, specificity 0.57). Adding more predictors did not improve the discriminant power., Conclusion: The combination of FPG and IGFBP-2 at early gestation (11-14 weeks) could predict later development of GDM with moderate discriminant power. Further validation studies are warranted to assess the utility of this simple combination model in other independent cohorts., (© 2024. The Author(s).)

Background: Accumulating evidence shows that free fatty acids (FFA) are associated with gestational diabetes mellitus (GDM). However, most of the studies focus on a few specific types of FFA, such as α-linolenic acid (C18:3n3) and Arachidonic acid (C20:4n6) or a total level of FFA., Objective: This study aimed to test the association between a variety of FFAs during the first trimester and the risk of GDM., Methods: The participants came from the Zhoushan Pregnant Women Cohort (ZWPC). A 1:2 nested case-control study was conducted: fifty mothers with GDM were matched with 100 mothers without GDM by age, pre-pregnancy body mass index (BMI), month of oral glucose tolerance test (OGTT) and parity. Thirty-seven FFAs (including 17 saturated fatty acids (SFA), 8 monounsaturated fatty acids (MUFA), 10 polyunsaturated fatty acids (PUFA) and 2 trans fatty acids (TFA)) in maternal plasma during the first trimester were tested by Gas Chromatography-Mass Spectrometry (GC-MS). Conditional logistic regression models were performed to assess the associations of FFA with the risk of GDM., Results: Nine FFAs were respectively associated with an increased risk of GDM (P < 0.05), and four FFAs were respectively associated with a decreased risk of GDM (P < 0.05). SFA risk score was associated with a greater risk of GDM (OR = 1.34, 95% CI: 1.12-1.60), as well as UFA risk score (OR = 1.26, 95% CI: 1.11-1.44), MUFA risk score (OR = 1.70, 95%CI: 1.27-2.26), PUFA risk score (OR = 1.32, 95%CI: 1.09-1.59) and TFA risk score (OR = 2.51, 95%CI: 1.23-5.13). Moreover, joint effects between different types of FFA risk scores on GDM were detected. For instance, compared with those with low risk scores of SFA and UFA, women with high risk scores of SFA and UFA had the highest risk of GDM (OR = 8.53, 95%CI: 2.41-30.24), while the Odds ratio in those with a low risk score of SFA and high risk score of UFA and those with a high risk score of SFA and low risk score of UFA was 6.37 (95%CI:1.33- 30.53) and 4.25 (95%CI: 0.97-18.70), respectively., Conclusion: Maternal FFAs during the first trimester were positively associated with the risk of GDM. Additionally, there were joint effects between FFAs on GDM risk., Condensation: Elevated FFA levels in the first trimester increased the risk of GDM., (© 2024. The Author(s).)

Background: Maternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG) were associated with SGA and LGA in GDM pregnancies and controls., Methods: Altogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fβ-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking., Results: In pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5-4.7) and 2.2 (95% CI 1.4-3.5) in the GDM group and 3.8 (95% CI 3.0-4.9) and 2.8 (95% CI 2.3-3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fβ-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8-3.1) in the control group. In fβ-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1-2.5) for LGA., Conclusion: Association with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fβ-hCG levels are associated with SGA only in non-GDM pregnancies., (© 2024. The Author(s).)

Introduction: To evaluate the role of aspartate aminotransferase to platelet ratio index (APRI) in the prediction of superimposed preeclampsia in chronic hypertensive pregnancy group in the first trimester., Methods: The present retrospective case-control study was conducted on 258 pregnant women, including 75 patients in the isolated chronic hypertension group, 92 in the superimposed preeclampsia group, and 91 low-risk pregnant women in the control group. APRI1 was calculated from routine blood test results in the first antenatal visit, and APRI2 was calculated from prelabor routine blood test results. APRI indices and other blood count parameters were evaluated and compared between groups and with the literature., Results: APRI1 was lower in the superimposed preeclampsia group than in the control and chronic hypertension groups, with p-values < 0.001. In the first trimester, platelet counts were higher in the superimposed preeclampsia group than in the hypertension and control groups. APRI2 was increased in the superimposed preeclampsia group compared to the control and chronic hypertension groups, with p-values 0.001 and 0.002, respectively. The optimal cut-off value for APRI1 was 0.036 (sensitivity 65.2 %, specificity 83.7 %), and for APRI2, it was found to be 0.057 (sensitivity 67.4 %, specificity 52.0 %) to predict superimposed preeclampsia., Discussion: To the best of our knowledge, this was the first study evaluating APRI in predicting superimposed preeclampsia in the first trimester. Increased platelet counts and lower APRI were found to be valuable indices for predicting superimposed preeclampsia. Further studies are needed to determine the utility of APRI in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Importance: There is no consensus regarding the best method for prediction of hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia., Objective: To determine predictive ability in early pregnancy of large-scale proteomics for prediction of HDP., Design, Setting, and Participants: This was a nested case-control study, conducted in 2022 to 2023, using clinical data and plasma samples collected between 2010 and 2013 during the first trimester, with follow-up until pregnancy outcome. This multicenter observational study took place at 8 academic medical centers in the US. Nulliparous individuals during first-trimester clinical visits were included. Participants with HDP were selected as cases; controls were selected from those who delivered at or after 37 weeks without any HDP, preterm birth, or small-for-gestational-age infant. Age, self-reported race and ethnicity, body mass index, diabetes, health insurance, and fetal sex were available covariates., Exposures: Proteomics using an aptamer-based assay that included 6481 unique human proteins was performed on stored plasma. Covariates were used in predictive models., Main Outcomes and Measures: Prediction models were developed using the elastic net, and analyses were performed on a randomly partitioned training dataset comprising 80% of study participants, with the remaining 20% used as an independent testing dataset. Primary measure of predictive performance was area under the receiver operating characteristic curve (AUC)., Results: This study included 753 HDP cases and 1097 controls with a mean (SD) age of 26.9 (5.5) years. Maternal race and ethnicity were 51 Asian (2.8%), 275 non-Hispanic Black (14.9%), 275 Hispanic (14.9%), 1161 non-Hispanic White (62.8% ), and 88 recorded as other (4.8%), which included those who did not identify according to these designations. The elastic net model, allowing for forced inclusion of prespecified covariates, was used to adjust protein-based models for clinical and demographic variables. Under this approach, no proteins were selected to augment the clinical and demographic covariates. The predictive performance of the resulting model was modest, with a training set AUC of 0.64 (95% CI, 0.61-0.67) and a test set AUC of 0.62 (95% CI, 0.56-0.68). Further adjustment for study site yielded only minimal changes in AUCs., Conclusions and Relevance: In this case-control study with detailed clinical data and stored plasma samples available in the first trimester, an aptamer-based proteomics panel did not meaningfully add to predictive utility over and above clinical and demographic factors that are routinely available.

Objective: Maternal postpartum depressive and anxiety symptoms are risk factors for subsequent maternal and child mental health problems. Little is known about the potential role of antepartum vitamin D and C-reactive protein (CRP) in the etiology of maternal postpartum affective symptoms. We investigated associations between antepartum vitamin D status and postpartum depressive and anxiety symptoms and whether antepartum CRP mediated these associations., Methods: In 2483 participants of the Amsterdam Born Children and their Development prospective cohort, maternal serum vitamin D and CRP were measured at a median of 13 weeks' gestation. Vitamin D status was defined as deficient (≤29.9 nM), insufficient (30-49.9 nM), sufficient (50-79.9 nM), or normal (≥80 nM). Maternal depressive symptoms (Center for Epidemiologic Studies-Depression) and anxiety (State-Trait Anxiety Inventory) were assessed 3 months postpartum., Results: After adjustments for confounders, vitamin D deficiency was only associated with increased postpartum anxiety symptoms ( B = 0.17, 95% confidence interval [CI] = 0.03-0.30, p = .017) compared to normal vitamin D levels (≥80 nM). In women not taking vitamin D supplementation ( n = 2303), vitamin D deficiency was associated with increased postpartum depressive and anxiety symptoms ( B = 0.14, 95% CI = 0.03-0.28, p = .045; and B = 0.17, 95% CI = 0.03-0.32, p = .015). Antepartum CRP did not mediate these links., Conclusions: We found some evidence that antepartum vitamin D deficiency was associated with increased postpartum affective symptoms, especially in women not taking vitamin D supplementation. Clinical trials should determine whether vitamin D supplementation can reduce the risk for postpartum affective disorders., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Psychosomatic Society.)

Objective: To evaluate combinations of candidate biomarkers to develop a multiplexed prediction model for identifying the viability and location of an early pregnancy. In this study, we assessed 24 biomarkers with multiple machine learning-based methodologies to assess if multiplexed biomarkers may improve the diagnosis of normal and abnormal early pregnancies., Design: A nested case-control design evaluated the predictive ability and discrimination of biomarkers in patients at risk of early pregnancy failure in the first trimester to classify viability and location., Setting: Three university hospitals., Patients: A total of 218 individuals with pain and/or bleeding in early pregnancy: 75 had an ongoing intrauterine gestation; 68 had ectopic pregnancies (EPs); and 75 had miscarriages., Interventions: Serum levels of 24 biomarkers were assessed in the same patients. Multiple machine learning-based methodologies to evaluate combinations of these top candidates to develop a multiplexed prediction model for the identification of a nonviable pregnancy (ongoing intrauterine pregnancy vs. miscarriage or EP) and an EP (EP vs. ongoing intrauterine pregnancy or miscarriage)., Main Outcome Measures: The predicted classification using each model was compared with the actual diagnosis, and sensitivity, specificity, positive predictive value, negative predictive value, conclusive classification, and accuracy were calculated., Results: Models using classification regression tree analysis using 3 (pregnancy-specific beta-1-glycoprotein 3 [PSG3], chorionic gonadotropin-alpha subunit, and pregnancy-associated plasma protein-A) biomarkers were able to predict a maximum sensitivity of 93.3% and a maximum specificity of 98.6%. The model with the highest accuracy was 97.4% (with 70.2% receiving classification). Models using an overlapping group of 3 (soluble fms-like tyrosine kinase-1, PSG3, and tissue factor pathway inhibitor 2) biomarkers achieved a maximum sensitivity of 98.5% and a maximum specificity of 95.3%. The model with the highest accuracy was 94.4% (with 65.6% receiving classification). When the models were used simultaneously, the conclusive classification increased to 72.7% with an accuracy of 95.9%. The predictive ability of the biomarkers in the random forest produced similar test characteristics when using 11 predictive biomarkers., Conclusion: We have demonstrated a pool of biomarkers from divergent biological pathways that can be used to classify individuals with potential early pregnancy loss. The biomarkers choriogonadotropin alpha, pregnancy-associated plasma protein-A, and PSG3 can be used to predict viability, and soluble fms-like tyrosine kinase-1, tissue factor pathway inhibitor 2, and PSG3 can be used to predict pregnancy location., Competing Interests: Declaration of Interests K.T.B. reports funding from NIH R01HD076279 and NIH ROI HD 110448 for the submitted work; funding from NIH ROI HD 110448 and NIH R01HD076279; patent pending outside the submitted work. K.J.B. has nothing to disclose. S.S. reports funding from National Institutes of Health, AbbVie, and Burroughs Wellcome Fund; Society for Assisted Reproductive Technology Research Committee Chair; Oncofertility Consortium Practice Committee outside the submitted work. P.T. reports funding from NIH ROI HD 110448 for the submitted work. J.C.R. has nothing to disclose. D.J.H. has nothing to disclose. L.A.B. has nothing to disclose. R.F.S. has nothing to disclose. N.C.K. has nothing to disclose. D.W.S. has nothing to disclose. J.C. has nothing to disclose. J.B. has nothing to disclose. Z.W. has nothing to disclose. Y.F. has nothing to disclose. M.K. reports funding from National research foundation of Korea; honorarium from Catholic university of Korea. S.M. reports funding from National Institutes of Health (UG3-OD035537) and PCORI (BPS-2022C3-30268); travel support from Society for Epidemiologic Research; Society for Epidemiologic Research Member at Large of the Executive Committee outside the submitted work. L.S. reports funding from R01 HD110448 for the submitted work; funding from IIS 1837964 RF1 AG063481 R01 LM013463 U01 AG068057 R01 AG058854 R01 AG071470 RF1 AG068191 U01 AG066833 R01 AG066833 P30 AG073105 R01 LM011176 - 09 R01 LM011176 - 09S1 R01 LM011176 - 09S2 R00 HG010905 R01 HD110448 U19 AG074879 LillyLRAP P30AG073105-03S2 outside the submitted work. P.G. has nothing to disclose., (Copyright © 2024. Published by Elsevier Inc.)