Search

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).)

Previous studies have investigated whether inflammatory cytokines in maternal circulation are associated with preterm birth. However, many have reported inconsistent results, and few have investigated cytokine trends through gestation, particularly with respect to subtypes of preterm birth. We explored levels of 15 inflammatory cytokines and growth factors in plasma and serum collected in the second (17-23 weeks, timepoint 1 (T1)) and third (28-32 weeks, timepoint 2 (T2)) trimesters with respect to subtypes of preterm birth: spontaneous preterm labour (sPTL), preterm premature rupture of membranes (PPROM), and medically indicated preterm birth (mPTB). The change in TNFα levels over time (T2/T1) significantly classified mPTB from term birth with an AUC of 0.79. While elevated sICAM-1 levels were significantly associated with sPTL, sICAM-1 was not an effective biomarker for prediction. While statistical differences in some biomarkers, such as TNFα and sICAM-1 were found, these are likely not clinically meaningful for prediction. These results did not reveal a relationship between spontaneous labour and circulating maternal inflammatory biomarkers, however, do suggest distinct inflammatory profiles between subtypes of preterm birth., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Hornaday 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.)

Objective: To retrospectively analyze the results of second-trimester serological prenatal screening and explore the factors which may influence the false-positive rate (FPR)., Methods: From January 2013 to December 2022, false-positive samples with follow-up outcomes from 632,825 second-trimester serological prenatal screening samples tested at Sichuan Provincial Maternity and Child Health Care Hospital were selected as the study group, while true-negative samples were 1 : 1 matched as the control group by propensity-score matching (PSM). Univariate and binary logistic regression models were used to analyze the influencing factors. This study was approved by the Medical Ethic Committee of Sichuan Provincial Maternity and Child Health Care Hospital (Ethic No. 20240607-270)., Results: The study and control groups were each matched with 305,998 cases. Univariate analysis showed that sampling season, the difference between ultrasound and gestational weeks calculated by last menstrual period (LMP), monthly median multiple of the median (mMoM) of alpha-fetoprotein (AFP), and monthly mMoM of free β -human chorionic gonadotropin (free β -hCG) were significantly different between the two groups (P < 0.05). Binary logistic regression analysis showed that Winter (OR = 0.938; 95%CI: 0.893 ~ 0.985), monthly AFP mMoM ≥ 1.11 (OR = 0.846; 95%CI: 0.761 ~ 0.941), monthly free β -hCG mMoM ≥ 0.89 (OR = 0.827; 95%CI: 0.737 ~ 0.929) are protective factors for FPR increase, whilst Spring (OR = 1.124; 95%CI: 1.072 ~ 1.179), Summer (OR = 1.121; 95%CI: 1.062 ~ 1.183), the difference between ultrasound and gestational weeks calculated by LMP of 8 ~ 14 days (OR = 1.319; 95%CI: 1.241 ~ 1.402), < 14 days (OR = 1.689; 95%CI: 1.542 ~ 1.850), monthly AFP mMoM of 0.90 ~ 0.94 (OR = 1.088; 95%CI: 1.046 ~ 1.131), and monthly free β -hCG mMoM of 1.05 ~ 1.10 (OR = 1.046; 95%CI: 1.000 ~ 1.094), ≥ 1.11 (OR = 1.062; 95%CI: 1.002 ~ 1.126) are risk factors for FPR increase., Conclusion: Sampling season, difference between ultrasound and gestational weeks by LMP, monthly AFP mMoM, and monthly free β -hCG mMoM are risk factors for FPR during serological prenatal screening. Screening laboratories should look for the cause of abnormal FPR through such factors and adjust them accordingly.

Objective: The objective of this study was to compare the levels of cathepsin B and pentraxin 3 in maternal serum of pregnant women with preeclampsia in the second trimester, to ascertain the impact of these levels on maternal and fetal outcomes, and to present a comprehensive analysis of the combined effects of cathepsin B and pentraxin 3 levels., Methods: This prospective case-control study was conducted at Bursa Yuksek Ihtisas Training and Research Hospital between 1 January 2022 and 31 December 2022. The study included 78 pregnant women diagnosed with preeclampsia and 78 healthy pregnant women in the second trimester, between the ages of 18 and 45. Once a diagnosis of preeclampsia was established, maternal serum samples were obtained from the pregnant women prior to the initiation of any therapeutic intervention. Once all samples had been collected, the values for cathepsin B and pentraxin 3 were determined using the ELISA method., Results: The results demonstrated a statistically significant elevation in the levels of pentraxin 3 ( p  = 0.008) and cathepsin B ( p  = 0.005) in pregnancies affected by preeclampsia when compared to those deemed healthy. Moreover, pentraxin-3 ( p  = 0.007) and cathepsin B ( p  = 0.002) were found to be significantly elevated in severe preeclampsia compared to mild preeclampsia. A comparison of the groups with and without HELLP syndrome revealed no statistically significant difference between the two groups. The ROC analysis revealed that the Cathepsin B 7.04 cut-off value was statistically significantly associated with the prediction of preeclampsia in all cases, with a sensitivity of 78.2% and a specificity of 47.4% ( p  = 0.005, AUC = 0.631)., Conclusion: The levels of CB and PTX3 may be employed as biomarkers to facilitate the early diagnosis of PE during the second trimester. Furthermore, these biomarkers may prove to be promising for the prediction of PE severity.

Aims: To verify whether hemoglobin A1c (HbA1c) levels in early pregnancy can predict the diagnosis of gestational diabetes mellitus (GDM) in mid-pregnancy., Materials and Methods: This was a retrospective cohort study of 2008 pregnant women who delivered singletons at the Yokohama City university Medical Center. Concomitant or history of diabetes mellitus and overt diabetes in pregnancy were excluded. Pregnant women at high risk for GDM underwent a one-step 75-g oral glucose tolerance test (OGTT) during mid-pregnancy. For other pregnant women, GDM was diagnosed by a two-step 75-g oral glucose tolerance test (OGTT) when the 50-g glucose challenge test result in mid-pregnancy was ≥140 mg/dL. The thresholds for 75-g OGTT followed those of the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria (92-180-153 mg/dL). The relationship between HbA1c level measured at <20 weeks of gestation and GDM diagnosis at mid pregnancy was assessed using a receiver operating characteristic curve (ROC); area under the curve (AUC) and optimal cutoff value of HbA1c, predictive of GDM were calculated., Results: The median HbA1c level at <20 weeks of gestation was 5.3%, and 8.5% of women were diagnosed with GDM. In the ROC curve of the GDM diagnosis rate by HbA1c level, AUC was 0.706, and the optimal cutoff value was 5.4%, with a sensitivity of 0.6176, specificity of 0.6834, positive predictive value of 15.4%, and negative predictive value of 95.1%., Conclusions: Although HbA1c at less than 20 weeks of gestation is acceptable discrimination as a diagnostic tool of GDM in mid-pregnancy, it is not clinically useful to predict GDM in mid-pregnancy., (© 2024 Japan Society of Obstetrics and Gynecology.)

Aims/introduction: This study aimed to evaluate the problems in screening for gestational diabetes mellitus (GDM) by casual blood glucose (CBG) measurements at 24-28 gestational weeks., Materials and Methods: Overall, 763 pregnant women who underwent the 50-g glucose challenge test (GCT) at 24-28 gestational weeks were enrolled. The preload blood glucose (0-h BG) level of 50-g GCT was considered as CBG., Results: A total of 240 women with BG levels at 1-h after loading (1-h BG) on 50-g GCT ≥140 mg/dL underwent the 75-g oral glucose tolerance test, and 98 (40.8%) were diagnosed with GDM. Of the 99 women with GDM, 71 (71.7%) had 0-h BG on 50-g GCT <100 mg/dL., Conclusions: This study, where pregnant women underwent both CBG and 50-g GCT simultaneously, showed that when CBG at 24-28 gestational weeks ≥100 mg/dL alone was used for screening GDM, many pregnant women with GDM were overlooked., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: To evaluate neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-monocyte ratio (NMR), and other hemogram-derived inflammatory parameters measured in the early second trimester and their association with the risk of gestational diabetes mellitus (GDM)., Methods: This case-control study was conducted with 105 women with GDM and 205 healthy pregnant women, matched for maternal age at a 1:2 ratio with the cases at two regional maternity hospitals between January 2021 and August 2022. The inflammatory blood cell indices were tested in the early second trimester, and the patient's characteristics and the course of the pregnancy were analyzed. Logistic regression was used to determine the association between hematological parameters and the risk of GDM. Data were analyzed using SPSS, version 25.0 (SPSS, Chicago, IL)., Results: The final analysis included 310 pregnant women. The GDM group showed a higher pre-pregnancy BMI compared to the healthy controls ( p  < .01). There was no difference in NMR, PLR, and NLR between the groups ( p  = .63, .54, and .39, respectively). GDM was only positively associated with MLR ( p  = .02). After adjusting for potential confounding risk factors including maternal age, parity, and BMI, the multivariate regression analysis showed a higher level of MLR, with a cutoff point of 0.312, was independently associated with the risk of GDM (OR = 2.15, 95%CI 1.51-4.31, p  = .03). However, ROC analysis showed that the AUC value of MLR was poor (0.670)., Conclusions: We found that MLR, an inflammatory combined index derived from whole blood counts, may potentially serve as a predictor of GDM in the early second trimester.

This study aimed to investigate the serum biochemical markers' propensity associated with sex chromosome abnormalities (SCAs) and assess the clinical efficacy of SCAs in serum biochemical screening during the second trimester. A retrospective case-control analysis was conducted on pregnant women who underwent serum biochemical screening during the second trimester. The study compared groups of women with SCAs to those with normal chromosome karyotypes to assess changes in biochemical markers. We analysed and compared the performance of serum biochemical screening in each SCA group. The results showed that the alterations in serum biochemical markers varied among the different SCA groups. Typically, the serum biochemical markers of fetal SCAs were either above the 95th percentile or below the 5th percentile. The proportions of high- and intermediate-risk findings for 45,X, 47,XXX, 47,XXY, 47,XYY, and mosaic sex chromosomal abnormalities were 43.48%, 78.95%, 63.89%, 70.59%, and 78.13%, respectively. Besides detecting fetal trisomy 21 and trisomy 18, the current contingent screening procedures may also accidentally identify various fetal SCAs at a rate of 69.18%., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Approval was granted by Sichuan University’s Institutional Ethics Committee (No.2024(073)). Consent to participate: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s).)

Background: Macrosomia, characterized by excessive fetal growth, is common in infants born to women with pre-gestational diabetes and gestational diabetes mellitus (GDM). However, macrosomia, which leads to birth-related maternal and fetal complications and metabolic complications in the adolescence of the affected fetuses, also occurs in the pregnancies of non-diabetic women. This study aims to identify the association between second-trimester lipid profiles and macrosomia in non-diabetic pregnant women to aid in early diagnosis., Methods: This retrospective cohort study included 8,956 patients who delivered at a tertiary care center between 2017 and 2019. Exclusion criteria encompassed pre-existing diabetes, GDM, preeclampsia (PE), intrahepatic cholestasis of pregnancy, obesity, fetal chromosomal or genetic abnormalities, tobacco, alcohol, or drug use affecting lipid metabolism. Participants were divided into two groups: 621 with macrosomia and 873 controls. Second trimester maternal lipid profiles and demographic variables such as age, pregnancy week, and gender were assessed., Results: In the study cohort, maternal age ( P =0.002), gestational week ( P =0.003), and cesarean section rate ( P <0.001) were higher in the macrosomic group. High-density lipoprotein-cholesterol (HDL-C) was significantly lower, while total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) were significantly higher in the macrosomic group ( P <0.001). Univariate analysis revealed positive associations between second-trimester TG (OR 1.023, 95% CI: 1.020‒1.033, P <0.001), TC (OR 1.023, 95% CI: 1.016‒1.030, P <0.001) and LDL-C (OR 1.036, 95% CI: 1.018-1.054, P <0.001) with macrosomia and a negative association with HDL-C (OR 0.954, 95% CI: 0.923‒0.976, P <0.001). However, after adjusted multivariable logistic analysis, only TG remained statistically significantly associated with macrosomia (OR 1.054, 95% CI: 1.033‒1.076, P <0.001)., Conclusion: Our study emphasizes the importance of early recognition and prevention of macrosomia. Structured prospective studies are needed to enhance macrosomia prediction and implement preventive measures, such as dietary modifications. These strategies will be crucial in preventing birth-related complications and long-term health risks, including diabetes, obesity, and cardiovascular diseases, associated with macrosomia., (© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

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.)

Objective: To assess the performance of continuous glucose monitoring (CGM)-measured glycemic metrics in predicting development of gestational diabetes mellitus (GDM) and select perinatal complications. Research Methods: In a prospective observational study, CGM data were collected from 760 pregnant females throughout gestation after study enrollment. GDM was diagnosed using the oral glucose tolerance test (OGTT) at 24-34 weeks of gestation. Predictive models were built using logistic and elastic net regression. Predictive performance was assessed by the area under the receiver-operating characteristic (AUROC) curve. Results: The AUROCs of using second trimester percent time >140 mg/dL (TA140) and week 13-14 TA140 in predicting GDM were 0.81 and 0.74, respectively. The AUROCs for predicting large-for-gestational-age (LGA) births and hypertensive disorders of pregnancy (HDP) using second trimester TA140 were both 0.58. When matching the specificity of OGTT, a model using TA140 in weeks 13-14 achieved similar sensitivity to OGTT in predicting HDP (13% vs. 10%, respectively) and LGA (6% for both methods). Elastic net also demonstrated similar AUROC and diagnostic performance with no meaningful improvement by using multiple predictors. Conclusion: CGM-measured hyperglycemic metrics such as TA140 predicted GDM with high AUROCs as early as 13-14 weeks of gestation. These metrics were also similar statistically to the OGTT at 24-34 weeks in predicting perinatal complications, although sensitivity was low for both. CGM could potentially be used as an early screening tool for elevated hyperglycemia during gestation, which could be used in addition to or instead of the OGTT.

Background: Antenatal depression (AD) is one of the most common pregnancy complications. Recent studies indicated that immune responses during pregnancy may contribute to development of AD., Objectives: This study aimed to identify possible inflammatory biomarkers in early pregnancy to predict maternal depressive symptoms before delivery., Methods: This case-control study was conducted within the Maternal and Infant Health (MI-Health) birth cohort (Beijing, China) and depressive symptoms were assessed by Zung Self-rating Depression Scale (SDS) in both second and third trimesters. By using immune multi-factors kits, we tested 26 inflammatory factors in the serum of 38 cases with antenatal depression symptoms in both trimesters (SDS ≥ 53) and 38 controls. Logistic regression was used to identify candidate biomarkers, and the predictive capabilities were evaluated by using Receiver Operator Characteristics (ROC) analysis., Results: The concentrations of ln(CCL24) (p = 0.020), IL-7 (p = 0.006) and IL-10 (p = 0.014) were higher in early pregnancy among women with depressive symptoms comparing to healthy controls. The difference remained statistically significant after adjusting for maternal age, education level, gestational diabetes mellitus, pre-pregnancy BMI and gestational weeks of blood sampling (OR(ln(CCL24)) = 4.625, OR(IL-7) = 1.414, OR(IL-10) = 1.151). In ROC analysis, ln(CCL24), IL-7, and IL-10 achieved discrimination for depressive symptoms antepartum, with the values of AUC estimated at 0.75., Limitations: The sample size is limited, and the infectious disease infection records were not collected for control., Conclusion: Higher levels of CCL24, IL-7 and IL-10 may indicate the higher risk of antenatal depression and are potential biomarkers indicating pathogenesis of antenatal depression., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

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).)

Objective: This research analyzes the potential of long non-coding RNAs (lncRNAs) as markers in determining the necessity of antiviral treatment in pregnant women by examining alterations in the expression profile of serum lncRNAs in pregnant women with elevated hepatitis B viral load (HBVL) under antiviral and non-antiviral treatment regimens between the second trimester and delivery., Methods: Serum was obtained from 6 s-trimester pregnant women with high HBVL and no intrauterine infection. Then, 3 of these women were randomly selected for antiviral treatment, with the remaining 3 women undergoing non-antiviral treatment as control. Serum samples were again collected from these 6 women before delivery. The expression profile of lncRNAs was analyzed with microarray technology, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The axes of hub lncRNA-miRNA-mRNA were identified based on the competing endogenous RNA (ceRNA) network., Results: The expression profile of serum lncRNAs in pregnant women with high HBVL changed significantly from the second trimester of pregnancy until delivery under antiviral or non-antiviral treatment. The Venn diagram was utilized to screen out the jointly up-regulated and down-regulated lncRNAs in the serum of pregnant women under antiviral and non-antiviral treatment before delivery. Additionally, the KEGG pathway enrichment analysis results showed that lncRNAs might mediate the Hippo pathway in HBV infection. Based on the ceRNA network, 3 hub lncRNAs (CATG00000076041.1, LINC01310, and G014655) were found to potentially regulate the key gene TP73 in the Hippo pathway., Conclusion: In this study, we retrieved co-differentially expressed lncRNAs in pregnant women with high HBVL under antiviral or non-antiviral treatment, which may be used as markers for evaluating whether pregnant women with high HBVL may be free of antiviral treatment. This study may provide a basis for preventing potential adverse effects of antiviral treatment on maternal and fetal health., (© 2024. The Author(s).)

Objective: This study aims to assess the prognostic and diagnostic value of inflammatory indexes related to gestational diabetes mellitus (GDM) from the second trimester to the third trimester of pregnancy., Materials and Methods: In this study, we randomly selected 65 pregnant women diagnosed with GDM at our hospital from December 2022 to June 2023 to form the GDM group (n = 65). Additionally, 65 pregnant women at the same gestational weeks without GDM were selected as the Normal group (n = 65). We collected gestational information and serum samples at 24 and 36 weeks of gestation from the participants. The levels of NLRP3, IL-1Ra, and TBP-2 were determined using enzyme-linked immunosorbent assay (ELISA) to explore their changes during pregnancy. Further, this study analyzed the changes in the levels of NLRP3, IL-1Ra, and TBP-2 at 24 and 36 weeks of gestation in GDM patients and their correlation with gestational diabetes mellitus., Results: The study showed that pre-pregnancy body mass index (BMI), neonatal weight, gestational hypertension, and macrosomia are significantly associated with the occurrence of GDM (P < 0.05). Statistical analysis comparing the normal and GDM groups found no significant changes in the levels of NLRP3, IL-1Ra, and TBP-2 with the progression of gestation in the normal group. In contrast, in the GDM group, the levels of IL-1Ra in serum samples at 24 and 36 weeks were significantly increased (P < 0.05) while the levels of NLRP3 and TBP-2 were significantly reduced (P < 0.05). At 36 weeks, there was a positive correlation between the levels of NLRP3, IL-1Ra, and TBP-2. Compared to the normal group, the overall levels of NLRP3, IL-1Ra, and TBP-2 in the GDM group were lower (P < 0.05) and the weight of the newborns was significantly correlated with these three indicators (P < 0.05), specifically newborn weight increased with the levels of NLRP3 and TBP-2 but decreased with the increase of IL-1Ra (P < 0.05). Multifactorial logistic regression analysis further revealed that NLRP3 is an independent factor influencing GDM (P < 0.05). ROC curve analysis of the NLRP3 level at 24 weeks of gestation found that NLRP3 has a good value in predicting GDM (AUC = 0.720, 95%CI 0.630-0.809, P < 0.001) and the combined prediction of NLRP3, IL-1Ra, and TBP-2 also showed a good predictive value for GDM., Conclusion: The changes in NLRP3, IL-1Ra, and TBP-2 persisted throughout the 24 to 36 weeks of gestation, playing an important role in predicting the occurrence of GDM and the weight of the newborn., (© 2024. The Author(s).)

Objective: To explore the relationship between changes in glycated hemoglobin (HbA1c) during the second and third trimesters and adverse pregnancy outcomes among women without hyperglycemia in pregnancy (HIP)., Research Design and Methods: A total of 1,057 pregnant women who underwent serum HbA1c and delivered at Women's Hospital, Zhejiang University School of Medicine from May 2022 to March 2023, were included in this study. They were divided into four groups. Associations were evaluated using multivariate logistic regression analysis., Results: In our study, an upward trend in HbA1c levels in the second trimester (HbA1c&#95;S) and third trimester (HbA1c&#95;T) among women without HIP was demonstrated. Multivariate logistics regression analysis showed significant associations: Pregnant women with HbA1c&#95;S<5.5 %, HbA1c&#95;T≥6.1 %, or with HbA1c&#95;S≥5.5 %, HbA1c&#95;T<6.1 % had a significant correlation with hypertensive disorders of pregnancy (HDP) (aOR:2.72, 95 %CI=1.24-5.97；aOR:2.59, 95 %CI=1.15-5.84). Furthermore, for each 1 % increase in the difference value of HbA1c between the second and third trimesters, the risk of HDP increased about 1.96 times, and the risk of delivering a large-for-gestational-age baby increased about 1.30 times., Conclusion: Among pregnant women without HIP, elevated HbA1c levels in the second or third trimester are associated with increased risks of adverse pregnancy outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhaoxia Liang reports financial support was provided by Medical and Health Technology Program of Zhejiang Province. Zhaoxia Liang reports financial support was provided by Key R&D Program of Zhejiang. If there are other authors, they 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 B.V. All rights reserved.)

This study aimed to evaluate the associations of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels at <24 weeks of gestation with hypertensive disorders of pregnancy (HDP) and compare the strengths of the associations of HDP with FPG and HbA1c levels. Totally, 1,178 participants were included in this prospective cohort study. HDP, FPG, HbA1c, and potential confounding factors were included in multiple logistic regression models. The number of HDP cases was 136 (11.5%). When FPG and HbA1c were included in the model separately, quartile 4 (Q4) of FPG (87-125 mg/dL) and HbA1c (5.2-6.3% [33-45 mmol/mol]) levels had higher odds of HDP than quartile 1. The odds ratios (ORs) were 1.334 (95% confidence interval [CI]: 1.002-1.775) for Q4 of FPG and 1.405 (95% CI: 1.051-1.878) for Q4 of HbA1c. When the participants were divided into two categories based on the cut-off value with the maximum Youden Index of FPG or HbA1c, the ORs for high FPG (≥84 mg/dL) or high HbA1c (≥5.2% [33 mmol/mol]) were 1.223 (95% CI: 1.000-1.496) and 1.392 (95% CI: 1.122-1.728), respectively. When both FPG and HbA1c were included in the model simultaneously, the statistical significance of Q4 of FPG disappeared, whereas that of HbA1c remained. In two-category models, the same results were obtained. High FPG and HbA1c levels at <24 weeks of gestation were risk factors for HDP in pregnant Japanese women. In addition, high HbA1c levels were more strongly associated with HDP than high FPG levels.

Aims/introduction: Women with gestational diabetes mellitus are at high risk for adverse maternal and neonatal outcomes. The study aimed to evaluate the performance of the triglyceride-glucose index in predicting the risk of developing adverse outcomes in women with gestational diabetes mellitus., Materials and Methods: This retrospective multicenter cohort study included 8,808 pregnant women with gestational diabetes mellitus in two grade-A tertiary hospitals in China during 2018-2022. The triglyceride-glucose index was defined as ln [triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. Significant adverse gestational diabetes mellitus outcomes were chosen by generalized linear models as the main outcomes. Multivariable logistic regression models evaluated their association with the triglyceride-glucose index. Areas under the receiver operating characteristic curves predicted adverse pregnancy outcomes. The prediction efficiency was validated in the sensitivity analysis dataset and validation cohort., Results: The triglyceride-glucose index was associated with preeclampsia, severe preeclampsia, preterm birth, placenta accreta spectrum, and macrosomia before and after adjusting for confounding factors (P < 0.05). The predictive performance of the triglyceride-glucose index was relatively moderate. Incorporating the triglyceride-glucose index into the baseline clinical risk model improved the area under curves for the diagnosis of preeclampsia (0.749 [0.714-0.784] vs 0.766 [0.734-0.798], P = 0.033) and macrosomia (0.664 [0.644-0.685] vs 0.676 [0.656-0.697], P = 0.002). These predictive models exhibited good calibration and robustness., Conclusions: The triglyceride-glucose index is positively associated with preeclampsia, severe preeclampsia, preterm birth, placenta accreta spectrum, and macrosomia and is useful for the early prediction and prevention of adverse outcomes in women with gestational diabetes mellitus., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: Conflicting associations have been noted between thyroid function and gestational diabetes mellitus (GDM), with indications that pre-pregnancy BMI might influence these relationships. This study aims to examine the effect of thyroid hormone indices and their mediation role on the risk of GDM., Methods: Pregnant women in our study were recruited from the Zhoushan Pregnant Women Cohort, Zhejiang Province, China. Participants who had their first prenatal follow-up and measured thyroid biomarkers in the first trimester, and oral glucose tolerance test (OGTT) records in the second trimester were eligible for inclusion in this study. The data were extracted from the Electronic Medical Record System database, at Zhoushan Maternal and Child Care Hospital. Maternal information about sociodemographic and health-related characteristics was extracted from the dataset. A unique personal identification number was provided to link both datasets. Multivariate logistic regression models were applied to investigate the correlations between thyroid hormone indices with GDM. The interaction effects of first-trimester thyroid hormone indices with pre-pregnancy BMI on GDM risk using a generalized linear regression model. Furthermore, the mediation analysis was used to explore the potential mediating effects of thyroid hormone indices on the relationship between pre-pregnancy BMI and GDM., Results: Overall, 5895 pregnant women were included in this study. The first-trimester FT4, thyroid feedback quantile-based index (TFQI), thyrotropin index (TSHI) and thyrotroph thyroxine resistance index (TT4RI) levels were negatively associated with fasting blood glucose (FBG) and postprandial blood glucose (PBG2H) in the second trimester (all P<0.05); FT3 and the FT3-to-FT4 ratio levels were positively associated with PBG1H and PBG2H in the second trimester (all P<0.05). Moreover, there were significant correlations between the highest quartile FT4, FT3, FT3-to-FT4 ratio, TSHI, and TFQI with GDM (all P < 0.05). The mediating effect of thyroid hormone parameters was 24.9% on the association between pre-pregnancy BMI and GDM., Conclusions: In conclusion, the low FT4, high FT3-to-FT4 ratio, and low TFQI in the first trimester significantly increase the risk of GDM and should be given more attention. Furthermore, increased pre-pregnancy BMI might partially increase the risk of GDM by influencing the body's thyroid function., 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 Alifu, Chen, Zhuang, Chi, Cheng, Qiu, Huang, Zhang, Ainiwan, Si, Peng, Zhou, Liu and Yu.)

Objective: To explore the association between serum levels and food intake of Vitamin D (VD) among healthy women in mid-pregnancy and preeclampsia., Study Design: In a Brazilian multicentre cohort of healthy nulliparous pregnant women from five maternity centres we developed a nested case-control analysis comparing cases with and without preeclampsia. Women were enrolled and followed during prenatal care, including only singleton pregnancies, without any fetal malformations or previous chronic maternal disease. We matched 87 cases of preeclampsia to eligible controls randomly selected in a 1:1 ratio, by age and region., Main Outcome Measures: Blood samples from these were collected, and a 24-hour recall of food intake was obtained in mid-pregnancy, between 19 and 21 weeks. VD serum levels (25-hydroxyvitamin D) were measured by liquid chromatography-tandem mass spectrometry and were categorized as deficient, insufficient, and sufficient. The dietary intake of VD was estimated with the 24-hour diet recall applied at the same time and from supplementation. Maternal characteristics and VD levels were compared between cases and controls with OR and respective 95 %CI. Multivariate analysis using the Path method was used to assess relationships among VD, PE, BMI, skin colour/ethnicity, and diet., Results: The maternal characteristics of both groups were similar, except for the higher occurrence of obesity among women with preeclampsia (OR 3.47, 95 %CI 1.48-8.65). Dietary intake of VD was similar in both groups, and most of the women in both groups consumed insufficient VD (82.2 vs 79.3 % in the groups with and without PE)., Conclusions: Levels and dietary intake of VD were not associated with PE in this Brazilian sample of healthy pregnant women; however, BMI and skin colour/ethnicity were associated with PE., 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.)

Purpose: To investigate the associations of choline, betaine, dimethylglycine (DMG), L-carnitine, and Trimethylamine-N-oxide (TMAO) with the risk of Gestational diabetes mellitus (GDM) as well as the markers of glucose homeostasis., Methods: We performed a case-control study including 200 diagnosed GDM cases and 200 controls matched by maternal age (±2 years) and gestational age (±2 weeks). Concentrations of serum metabolites were measured by the high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS)., Results: Compared to the control group, GDM group had significantly lower serum betaine concentration and betaine/choline ratio, and higher DMG concentration. Furthermore, decreased betaine concentration and betaine/choline ratio, increased DMG concentration showed significant association with the risk of GDM. In addition, serum betaine concentrations were negatively associated with blood glucose levels at 1-h post-glucose load (OGTT-1h), and both betaine and L-carnitine concentrations were positively associated with 1,5-anhydroglucitol levels. Betaine/choline ratio was negatively associated with OGTT-1h and blood glucose levels at 2-h post-glucose load (OGTT-2h) and serum choline concentrations were negatively associated with fasting blood glucose and positively associated with OGTT-2h., Conclusion: Decreased serum betaine concentrations and betaine/choline ratio, and elevated DMG concentrations could be significant risk factors for GDM. Furthermore, betaine may be associated with blood glucose regulation and short-term glycemic fluctuations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To explore the association between the concentration of maternal serum biomarkers and the risk of fetal carrying chromosome copy number variants (CNVs)., Methods: Pregnant women identified as high risk in the second-trimester serological triple screening and underwent traditional amniotic fluid karyotype analysis, along with comparative genomic hybridization array (aCGH)/copy number variation sequencing (CNV-seq), were included in the study. We divided the concentration of serum biomarkers, free beta-human chorionic gonadotropin (fβ-hCG), alpha fetoprotein (AFP) and unconjugated estriol (uE3), into three levels: abnormally low, normal and abnormally high. The prevalence of abnormally low, normal and abnormally high serum fβ-hCG, AFP and uE3 levels in pregnant women with aberrant aCGH/CNV-seq results and normal controls was calculated., Results: Among the 2877 cases with high risk in the second-trimester serological triple screening, there were 98 chromosome abnormalities revealed by karyotype analysis, while 209 abnormalities were detected by aCGH/CNVseq (P＜0.001) . The carrying rate of aberrant CNVs increased significantly when the maternal serum uE3 level was less than 0.4 multiple of median (MoM) of corresponding gestational weeks compared to normal controls, while the carrying rate of aberrant CNVs decreased significantly when the maternal serum fβ-hCG level was greater than 2.5 MoM compared to normal controls. No significant difference was found in the AFP group., Conclusion: Low serum uE3 level (<0.4 MoM) was associated with an increased risk of aberrant CNVs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Increased adiposity during pregnancy may be related to offspring risk for mental health disorders, although the biological mechanisms are poorly understood. One promising hypothesis is that factors secreted from adipocytes such as leptin and adiponectin may explain this association. The current study examined whether pregnancy or umbilical cord blood concentrations of leptin and/or adiponectin a) predict elevated infant negative affect at 6 months (an early life marker of risk for psychopathology); and b) help explain the association between pregnancy adiposity and increased infant negative affect., Methods: Data came from a prospective cohort (N = 305) of pregnant individuals and their offspring. Second trimester adiposity was assessed using air displacement plethysmography. Concentrations of leptin and adiponectin were measured in second trimester plasma and umbilical cord plasma. Infant negative affect was assessed by standardized observation at 6 months. Second trimester inflammation was assessed using a comprehensive panel of cytokines., Results: Lower second trimester adiponectin was associated with elevated infant negative affect, and mediated the effect of pregnancy adiposity on infant negative affect. This association was independent of the effect of second trimester inflammation. Umbilical cord leptin also predicted higher infant negative affect and mediated the association between pregnancy adiposity and infant negative affect., Conclusions: This is the first study to link pregnancy adiponectin or cord blood leptin to infant markers of risk for psychopathology, and the first to demonstrate that these adipokines mediate the association between pregnancy adiposity and offspring behavioral outcomes, suggesting novel markers of risk and potential mechanisms of effect., Competing Interests: Declaration of competing interest We have no known conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess a panel of cytokines and placental insufficiency with the risk of preterm delivery (PTD)., Methods: Nested case-control study into the BRISA birth cohort. Eighty-two mother-infant-placenta pairs were selected at 20 +0 to 25 +6 weeks. Circulating biomarker levels were performed using Luminex flowmetric xMAP technology. Cytokines classified as Th1, Th2 or Th17 and other biomarkers were selected. The ratio between birth weight and placental weight (BW/PW) was used as a proxy for placental efficiency. Spearman correlation, univariate analyses and logistic regression models were calculated. Sensitivity, specificity, positive and negative likelihood ratios were calculated using the Receiver Operating Characteristic curve., Results: Mean gestational age was 250 days, 14,6% were small for gestational age, 4,8% large for gestational age and 13,4% stunted. Placental efficiency was higher for term newborns (p<0,001), and 18/22 (81%) preterm biomarker values were higher than the control group. Th1 cytokines were highly correlated, while the weakest correlation was observed in other biomarkers. Less education was associated with a higher risk of PTD (p = 0.046), while there was no appreciable difference in the risk of PTD for placental insufficiency. Biomarkers showed negligible adjusted OR of PTD (0.90 to 1.02). IL-6, IL-8, IL-1β, TNFβ, IL-4, IL-13, GCSF, MIP1A, VEGF, EGF, and FGF2 presented a higher sensitivity ranging from 75.56% to 91.11%., Conclusion: IL-8, IL-12p40, IL-4, IL-13, GCSF, MIP1B, and GMSF in asymptomatic pregnant women were associated with PTD. This finding suggests an activation of maternal inflammatory response., Competing Interests: Conflicts to interest: none to declare.

Background: Fluoride exposure during pregnancy has been associated with various effects on offspring, including changes in behavior and IQ. To provide clues to possible mechanisms by which fluoride may affect human fetal development, we completed proteomic analyses of cord blood serum collected from second-trimester pregnant women residing in northern California, USA., Objective: To identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women., Methods: The proteomes of 19 archived second-trimester cord blood samples from women living in northern California, USA, and having varied serum fluoride concentrations, were analyzed by quantitative mass spectrometry. The 327 proteins that were quantified were characterized by their abundance relative to maternal serum fluoride concentration, and subjected to pathway analyses using PANTHER and Ingenuity Pathway Analysis processes., Results: Pathway analyses showed significant increases in process related to reactive oxygen species and cellular oxidant detoxification, associated with increasing maternal serum fluoride concentrations. Pathways showing significant decreases included complement cascade, suggesting alterations in alterations in process associated with inflammation., Conclusion: Maternal fluoride exposure, as measured by serum fluoride concentrations in a small, but representative sample of women from northern California, USA, showed significant changes in the second trimester cord blood proteome relative to maternal serum fluoride concentration., (© 2024. The Author(s).)

Background: Accumulating evidence has linked dyslipidemia during pregnancy to the risk of delivering infants born either large for gestational age (LGA) or small for gestational age (SGA). However, the effects of the vitamin D status on these relationships require further investigation. This study investigated whether the relationship between lipid profiles and the risk of LGA or SGA was influenced by vitamin D levels during the second trimester., Methods: Maternal lipid profile levels, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and vitamin D levels, were measured in a cohort of 6,499 pregnant women during the second trimester. Multivariate regression models and subgroup analyses were employed to evaluate the potential associations between maternal lipid profiles, vitamin D levels, and the risk of LGA or SGA., Results: The prevalence of SGA infants was 9.8% (n=635), whereas that of LGA infants was 6.9% (n=447). Maternal TG levels were found to be positively associated with the risk of LGA (odds ratio [OR] = 1.41, 95% confidence interval [CI]:1.17-1.70), whereas a negative association was observed between maternal TG, TC, LDL-C levels, and risk of SGA. Additionally, mothers with higher HDL-C levels were less likely to give birth to an LGA infant (OR=0.58, 95% CI:0.39-0.85). Importantly, associations between TG, TC, LDL-c, and SGA as well as between TG and LGA were primarily observed among pregnant women with insufficient vitamin D levels. As for HDL-C, the risk of LGA was lower in mothers with sufficient vitamin D (OR = 0.42, 95% CI:0.18-0.98) compared to those with insufficient vitamin D (OR = 0.65, 95% CI:0.42-0.99)., Conclusion: Vitamin D status during the second trimester exerts a modifying effect on the association between lipid profiles and the risk of LGA and SGA infants., 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 Zheng, Lai, Liu, Chen, Zhang, Wu, Luo and Gu.)

Introduction: Maternal nutritional and vitamin status during pregnancy may have long-term effects on offspring health and disease. The aim of this study was to examine the associations between maternal vitamin A and D status in pregnancy and offspring bone mineral content (BMC) at nine years of age., Methods: This is a post-hoc study of a randomized control trial including 855 pregnant women from two Norwegian cities; Trondheim and Stavanger. The women were randomized into an exercise intervention or standard antenatal care. Mother and child pairs for the present study were recruited from those still living in Trondheim after 8-10 years. Serum vitamin A (retinol) and vitamin D (25(OH)D) were measured in the 2 nd and 3 rd trimesters of pregnancy, and active vitamin D (1,25(OH) 2 D) in serum was measured in a subgroup. Spine BMC and trabecular bone score were measured in the children at nine years of age. Associations were analyzed with linear regression models., Results: A total of 119 mother and child pairs were included in the analyses. Vitamin A insufficiency (retinol < 1.05 µmol/L) and vitamin D deficiency (25(OH)D < 50 mmol/L) increased from ~7% to ~43% and from ~28% to ~33%, respectively, from the 2 nd to the 3 rd trimester. An increase in serum 1,25(OH) 2 D from the 2 nd to the 3 rd trimester was observed in the subgroup. There was a negative association between serum retinol in the 2 nd trimester and spine BMC in the boys, but not in the girls, when adjusted for maternal and child confounders. No other associations between maternal serum vitamin A or D and BMC in the children were found., Conclusion: We observed a high prevalence of vitamin A insufficiency and vitamin D deficiency during pregnancy. A negative association between mid-pregnancy vitamin A status and spine BMC was observed in boys, but not girls, while no associations were found between maternal vitamin D status and child BMC. The implications of optimal vitamin A and D status in pregnancy for offspring bone health, remains a subject for further investigations., 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 Stunes, Mosti, Gustafsson, Børsting, Thorsby, Stafne and Syversen.)

Background: Small-for-gestational-age (SGA), commonly caused by poor placentation, is a major contributor to global perinatal mortality and morbidity. Maternal serum levels of placental protein and angiogenic factors are changed in SGA. Using data from a population-based pregnancy cohort, we estimated the relationships between levels of second-trimester pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF), and serum soluble fms-like tyrosine kinase-1 (sFlt-1) with SGA., Methods: Three thousand pregnant women were enrolled. Trained health workers prospectively collected data at home visits. Maternal blood samples were collected, serum aliquots were prepared and stored at -80℃. Included in the analysis were 1,718 women who delivered a singleton live birth baby and provided a blood sample at 24-28 weeks of gestation. We used Mann-Whitney U test to examine differences of the median biomarker concentrations between SGA (< 10th centile birthweight for gestational age) and appropriate-for-gestational-age (AGA). We created biomarker concentration quartiles and estimated the risk ratios (RRs) and 95% confidence intervals (CIs) for SGA by quartiles separately for each biomarker. A modified Poisson regression was used to determine the association of the placental biomarkers with SGA, adjusting for potential confounders., Results: The median PlGF level was lower in SGA pregnancies (934 pg/mL, IQR 613-1411 pg/mL) than in the AGA (1050 pg/mL, IQR 679-1642 pg/mL; p < 0.001). The median sFlt-1/PlGF ratio was higher in SGA pregnancies (2.00, IQR 1.18-3.24) compared to AGA pregnancies (1.77, IQR 1.06-2.90; p = 0.006). In multivariate regression analysis, women in the lowest quartile of PAPP-A showed 25% higher risk of SGA (95% CI 1.09-1.44; p = 0.002). For PlGF, SGA risk was higher in women in the lowest (aRR 1.40, 95% CI 1.21-1.62; p < 0.001) and 2nd quartiles (aRR 1.30, 95% CI 1.12-1.51; p = 0.001). Women in the highest and 3rd quartiles of sFlt-1 were at reduced risk of SGA delivery (aRR 0.80, 95% CI 0.70-0.92; p = 0.002, and aRR 0.86, 95% CI 0.75-0.98; p = 0.028, respectively). Women in the highest quartile of sFlt-1/PlGF ratio showed 18% higher risk of SGA delivery (95% CI 1.02-1.36; p = 0.025)., Conclusions: This study provides evidence that PAPP-A, PlGF, and sFlt-1/PlGF ratio measurements may be useful second-trimester biomarkers for SGA., (© 2024. The Author(s).)

Background: A retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15-20 +6  weeks) of free beta human chorionic gonadotropin (free β-hCG). And the study was conducted to explore the relationship between maternal serum free β-hCG and adverse pregnancy outcomes (APO)., Methods: We retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free β-hCG group (free β-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free β-hCG < 2.50 MoM) from a total of 22,745 singleton pregnancies, and modified Poisson regression analysis was used to calculate risk ratios (RRs) and 95% confidence intervals (CI) of the two groups., Results: The gravidity and parity in the elevated free β-hCG group were lower, and the differences between the groups were statistically significant (all, P < 0.05). The risks of polyhydramnios, preeclampsia, and hyperlipidemia, were increased in women with elevated free β-hCG levels (RRs: 1.996, 95% CI: 1.322-3.014; 1.469, 95% CI: 1.130-1.911 and 1.257, 95% CI: 1.029-1.535, respectively, all P < 0.05), intrauterine growth restriction (IUGR) and female infants were also likely to happen (RRs = 1.641, 95% CI: 1.103-2.443 and 1.101, 95% CI: 1.011-1.198, both P < 0.05). Additionally, there was an association between elevated AFP and free β-hCG levels in second-trimester (RR = 1.211, 95% CI: 1.121-1.307, P < 0.001)., Conclusions: APOs, such as polyhydramnios, preeclampsia, and hyperlipidemia, were increased risks of elevated free β-hCG levels, IUGR and female infants were also likely to happen. Furthermore, there was an association between elevated AFP levels and elevated free β-hCG levels in second-trimester. We recommend prenatal monitoring according to the elevated maternal serum free β-hCG level and the occurrence of APO., (© 2024. The Author(s).)

Background/aims: Pregnant women are exposed to persistent environmental contaminants, including per- and polyfluoroalkyl substances (PFAS) that disrupt thyroid function. However, it is unclear if PFAS alter maternal sex-steroid hormone levels, which support pregnancy health and fetal development., Methods: In Illinois women with relatively high socioeconomic status (n = 460), we quantified perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid, perfluorohexanesulphonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid concentrations in fasting serum samples at median 17 weeks gestation, along with plasma progesterone, testosterone, and estradiol. We evaluated covariate-adjusted associations of ln-transformed hormones with each ln-transformed PFAS individually using linear regression and with the PFAS mixture using quantile-based g-computation (QGComp)., Results: Interquartile range (IQR) increases in PFOS were associated with higher progesterone (%Δ 3.0; 95%CI: -0.6, 6.6) and estradiol (%Δ: 8.1; 95%CI: 2.2, 14.4) levels. Additionally, PFHxS was positively associated with testosterone (%Δ: 10.2; 95%CI: 4.0, 16.7), whereas both PFDeA and PFUdA were inversely associated with testosterone (%Δ: -5.7; 95%CI: -10.3, -0.8, and %Δ: -4.1; 95%CI: -7.6, -0.4, respectively). The IQR-standardized PFAS mixture was not associated with progesterone (%Δ: 1.6; 95%CI: -5.8, 9.2), due equal partial positive (%Δ: 9.2; driven by PFOA) and negative (%Δ: -7.4; driven by PFOS) mixture associations. Similarly, the mixture was not associated with testosterone (%Δ: 5.3; 95%CI: -9.0, 20.1), due to similar partial positive (%Δ: 23.6; driven by PFHxS) and negative (%Δ: -17.4; driven by PFDeA) mixture associations. However, we observed a slightly stronger partial positive (%Δ: 25.6; driven by PFOS and PFUdA) than negative (%Δ: -16.3; driven by PFOA) association resulting in an overall non-significant positive trend between the mixture and estradiol (%Δ: 8.5; 95%CI: -3.7, 20.9)., Conclusion: PFAS mixture modeled using QGComp was not associated with maternal sex-steroid hormones due to potential opposing effects of certain PFAS. Additional prospective studies could corroborate these findings., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background and Objectives : Pregnancy introduces various interfering factors that, alongside individual variations, impact the assessment of thyroid function tests. This underscores the necessity of defining trimester-specific reference intervals for thyroid-stimulating hormone (TSH) levels. Differences in population characteristics, including ethnicity, socio-economic factors, iodine prophylaxis, and obesity, emphasize the need to establish trimester-specific TSH ranges for women of reproductive age in the respective region or center. The aim of the present study was to establish first- and second-trimester-specific reference intervals for TSH and free thyroxine (FT4) in a relevant pregnant population. Materials and Methods : A retrospective monocenter analysis utilized the electronic database of Ob/Gyn Hospital "Dr. Shterev", Sofia, Bulgaria. The analysis involved data from 497 pregnant and 250 non-pregnant women, all without evidence of thyroid dysfunction or a family history thereof, no indication of taking medication interfering with thyroid function, no evidence of levothyroxine treatment, and no history of sterility treatment. To establish the limits of the TSH reference range, the percentile method was applied using a bootstrapping procedure following the recommendations of the International Federation of Clinical Chemistry (IFCC). Results : Trimester-specific reference intervals for TSH and FT4 in our center were established as follows: first trimester-0.38-2.91 mU/L, FT4-12.18-19.48 pmol/L; second trimester-0.72-4.22 mIU/L and 9.64-17.39 pmol/L, respectively. We also established the normal reference range for the non-pregnant control group, which is similar to that applicable in our laboratory. Conclusions : Our results differ from the fixed limits recommended by the American Thyroid Association, European Thyroid Association, and Endocrine Society Guidelines. Following the relevant established intervals would significantly impact timely diagnosis and therapy requirements for a substantial proportion of pregnant women.

Associations between maternal immune dysregulation (including autoimmunity and skewed cytokine/chemokine profiles) and offspring neurodevelopmental disorders such as autism have been reported. In maternal autoantibody-related autism, specific maternally derived autoantibodies can access the fetal compartment to target eight proteins critical for neurodevelopment. We examined the relationship between maternal autoantibodies to the eight maternal autoantibody-related autism proteins and cytokine/chemokine profiles in the second trimester of pregnancy in mothers of children later diagnosed with autism and their neonates' cytokine/chemokine profiles. Using banked maternal serum samples from 15 to 19 weeks of gestation from the Early Markers for Autism Study and corresponding banked newborn bloodspots, we identified three maternal/offspring groups based on maternal autoantibody status: (1) mothers with autoantibodies to one or more of the eight maternal autoantibody-related autismassociated proteins but not a maternal autoantibody-related autism-specific pattern, (2) mothers with a known maternal autoantibody-related autism pattern, and (3) mothers without autoantibodies to any of the eight maternal autoantibody-related autism proteins. Using a multiplex platform, we measured maternal second trimester and neonatal cytokine/chemokine levels. This combined analysis aimed to determine potential associations between maternal autoantibodies and the maternal and neonatal cytokine/chemokine profiles, each of which has been shown to have implications on offspring neurodevelopment independently., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: This study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype., Materials and Methods: A prospective pregnancy cohort study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5-methyltetrahydrofolate (5-MTHF), 5, 10-methylene-tetrahydrofolate (5,10-CH2-THF), 5- formyltetrahydrofolate (5-CHO-THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5-MTHF, and methylmalonic acid (MMA), were determined at 6-17 weeks and 20-26 weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28 weeks of pregnancy by a 75-g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders., Results: The study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI]) = 1.36 (1.01-1.84)], UMFA ≥ P90 [aOR (95% CI) = 1.82 (1.23-2.69)], and HCY ≥ P75 [aOR (95% CI) = 1.40 (1.04-1.88)] in early pregnancy, and RBC 5-MTHF [aOR (95% CI) = 1.48 (1.10-2.00)], RBC 5,10-CH2-THF [aOR (95% CI) = 1.55 (1.15-2.10)], and plasma 5-MTHF [aOR (95% CI) = 1.36 (1.00-1.86)] in mid-pregnancy ≥ P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1-h and 2-h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5- MTHF and 5,10-CH2-THF, and plasma 5- MTHF in mid-pregnancy are positively associated with the 1-h glucose level (p < 0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM., Conclusions: Elevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5-MTHF and 5,10-CH2-THF and plasma 5-MTHF during mid-pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM., (© 2024 John Wiley & Sons Ltd.)

Prediction of women at high risk of preeclampsia is important for prevention and increased surveillance of the disease. Current prediction models need improvement, particularly with regard to late-onset preeclampsia. Preeclampsia shares pathophysiological entities with cardiovascular disease; thus, cardiovascular biomarkers may contribute to improving prediction models. In this nested case-control study, we explored the predictive importance of mid-pregnancy cardiovascular biomarkers for subsequent preeclampsia. We included healthy women with singleton pregnancies who had donated blood in mid-pregnancy (~ 18 weeks' gestation). Cases were women with subsequent preeclampsia (n = 296, 10% of whom had early-onset preeclampsia [< 34 weeks]). Controls were women who had healthy pregnancies (n = 333). We collected data on maternal, pregnancy, and infant characteristics from medical records. We used the Olink cardiovascular II panel immunoassay to measure 92 biomarkers in the mid-pregnancy plasma samples. The Boruta algorithm was used to determine the predictive importance of the investigated biomarkers and first-trimester pregnancy characteristics for the development of preeclampsia. The following biomarkers had confirmed associations with early-onset preeclampsia (in descending order of importance): placental growth factor (PlGF), matrix metalloproteinase (MMP-12), lectin-like oxidized LDL receptor 1, carcinoembryonic antigen-related cell adhesion molecule 8, serine protease 27, pro-interleukin-16, and poly (ADP-ribose) polymerase 1. The biomarkers that were associated with late-onset preeclampsia were BNP, MMP-12, alpha-L-iduronidase (IDUA), PlGF, low-affinity immunoglobulin gamma Fc region receptor II-b, and T cell surface glycoprotein. Our results suggest that MMP-12 is a promising novel preeclampsia biomarker. Moreover, BNP and IDUA may be of value in enhancing prediction of late-onset preeclampsia., (© 2024. The Author(s).)

Aim: This study aims to determine whether second-trimester uterine artery (UtA) Doppler combined with first-trimester abnormal pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-Hcg) levels predicts adverse obstetric and neonatal outcomes., Materials and Methods: This study of 289 pregnant women included 196 with normal PAPP-A and free β-HCG values (control group) and 93 with abnormal values (study group) in the first-trimester screening test. Second-trimester UtA Doppler sonography was done in these pregnancies. The perinatal prediction and screening potential of UtA Doppler pulsatility index (PI) parameters were examined in the study group., Results: UtA PI >95 percentile increased birth before the 37th week by 4.46 times, birth before the 34th week by 7.44 times, preeclampsia risk by 3.25 times, fetal growth restriction (FGR) risk by 4.89 times, and neonatal intensive care unit (NICU) admission rates by 3.66 times in the study group (p < 0.05 for all). UtA PI >95 percentile had 49.2% sensitivity and 82.1% specificity for birth before 37 weeks. For birth before 34 weeks, sensitivity was 80.0% and specificity 65.0%. FGR has 70.5% sensitivity and 67.1% specificity. Screening for preeclampsia has 66.6% sensitivity and 61.9% specificity., Conclusion: Adding UtA Doppler in the second trimester to pregnancies with abnormal PAPP-A and/or free β-Hcg values in the first trimester may be a useful screening method for adverse outcomes., (© 2024 Wiley Periodicals LLC.)

Objectives: First, to evaluate the predictive performance for preterm growth-related neonatal morbidity of a high soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio or low PlGF at midgestation and, second, to compare the performance of a high sFlt-1/PlGF ratio or low PlGF with that of the competing-risks model for small-for-gestational age (SGA), utilizing a combination of maternal risk factors, sonographic estimated fetal weight and uterine artery pulsatility index., Methods: This was a prospective observational study in women attending for a routine hospital visit at 19-24 weeks' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, carrying out an ultrasound scan and measuring serum PlGF and sFlt-1. The primary outcome was delivery < 32 and < 37 weeks' gestation of a SGA neonate with birth weight < 10 th or < 3 rd percentile, combined with neonatal unit (NNU) admission for ≥ 48 h or a composite of major neonatal morbidity. The detection rates in screening by PlGF < 10 th percentile, sFlt-1/PlGF ratio > 90 th percentile and the competing-risks model for SGA were estimated and then compared using McNemar's test., Results: In the study population of 40 241 women, prediction of preterm growth-related neonatal morbidity provided by the competing-risks model for SGA was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF ratio. For example, at a screen-positive rate of 10.0%, as defined by the sFlt-1/PlGF ratio > 90 th percentile, the competing-risks model predicted 70.1% (95% CI, 61.0-79.2%) of SGA < 10 th percentile and 76.9% (95% CI, 67.6-86.3%) of SGA < 3 rd percentile with NNU admission for ≥ 48 h delivered < 32 weeks' gestation. The respective values for SGA with major neonatal morbidity were 73.8% (95% CI, 64.4-83.2%) and 77.9% (95% CI, 68.0-87.8%). These were significantly higher than the respective values of 35.1% (95% CI, 25.6-44.6%), 35.9% (95% CI, 25.3-46.5%), 38.1% (95% CI, 27.7-48.5%) and 39.7% (95% CI, 28.1-51.3%) achieved by the application of the sFlt-1/PlGF ratio > 90 th percentile (all P < 0.0001)., Conclusion: At midgestation, the prediction of growth-related neonatal morbidity by the competing-risks model for SGA is superior to that of a high sFlt-1/PlGF ratio or low PlGF. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Background: Dietary imbalance, such as a lower proportion of complex carbohydrates and a higher protein diet, may contribute to gestational diabetes mellitus (GDM) risks through their metabolisms. However, there is a lack of knowledge regarding the association between butyrate, iso-butyrate, and GDM, which are metabolisms of the two primary nutrients above. This study aimed to clarify the association of butyrate and iso-butyrate with GDM., Methods: A nested case-control study was conducted based on the Beijing Birth Cohort Study (BBCS) from 2017 to 2018. Totally, 99 singleton women were involved (GDM: n = 49, control: n = 50). All participants provided blood samples twice (in their first and second trimesters). Gas chromatography-mass spectrometry (GC-MS) was used for butyrate and iso-butyrate detection. Unconditional logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis., Results: The results showed that butyrate in the first trimester was negatively correlated with GDM (odds ratio (OR): 0.00, 95% confidential interval (CI): 0.00-0.21, P = 0.008), and iso-butyrate in the second trimester was positively related to GDM (OR: 627.68, 95% CI: 40.51-9724.56, P < 0.001). The ratio (butyrate/iso-butyrate) was negatively associated with GDM, both in the first trimester (OR: 0.00, 95%CI: 0.00-0.05, P < 0.001) and in the second trimester (OR: 0.52, 95% CI: 0.34-0.80, P = 0.003). The area under the curve (AUC) using the ratio in the first trimester combined with clinical risk factors achieved 0.89 (95% CI: 0.83-0.95). Iso-butyrate in the second trimester combined with clinical risk factors achieved an AUC of 0.97 (95% CI: 0.92-1.00)., Conclusions: High iso-butyrate and low butyrate levels may be associated with an increased risk of GDM. As they are produced through dietary nutrient formation by gut microbiota, further studies on the association of dietary intake and butyrate or iso-butyrate concentration in plasma may help find a novel approach to nutritional intervention for GDM., (© 2024. The Author(s).)

Background: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes., Objectives: To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity., Methods: In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters - adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity., Results: We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity - compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories., Conclusion: Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aimed to examine the association between sleep behaviors and cardiovascular health (CVH) during pregnancy and test whether high-sensitivity C-reactive protein (hs-CRP) mediates this association., Methods: The study included 4204 pregnant women from the Maternal and Infant Health cohort study in Hefei (MIH-Hefei). Information on sleep (chronotype, sleep duration, snoring, daytime sleepiness, and insomnia) was collected through a touch-screen structured questionnaire at 16-23 weeks' gestation. CVH (body mass index, blood pressure, total cholesterol, glucose, and smoking) and hs-CRP were measured at 24-28 weeks' gestation. The role of hs-CRP in the association between sleep and CVH was explored in a mediation analysis, while adjusting for multiple confounding factors., Results: Poor sleep score was significantly associated with poor gestational CVH metrics, including an RR of 0.872 (95% CI, 0.810, 0.938) for having all ideal (vs. any nonideal) CVH metrics; hs-CRP level was significantly associated with poor gestational CVH metrics, including an RR of 0.531 (95% CI, 0.432, 0.609) for having all ideal (vs. any nonideal) CVH metrics. Sleep scores were positively correlated with hs-CRP level (β, 0.020, 95% CI, 0.006, 0.034). Mediation analysis revealed that the association between sleep and CVH mediated by hs-CRP was 12.31% (indirect effect, -0.0095, 95% CI, -0.0167, -0.0042)., Conclusions: Poor sleep during pregnancy, particularly late chronotype and snoring, may worsen CVH by increasing systemic chronic inflammation., (Copyright © 2023 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Sparse data exists on the utility of individual serum non-esterified fatty acids (NEFAs) as clinical and dietary biomarkers and how reporting methods could affect these associations. We investigated the associations of 19 serum NEFAs expressed as µM or mol%, with self-reported dietary intake data, and cardiometabolic health indicators in pregnant women., Methods: In this cross-sectional study, 273 pregnant women in their second trimester each completed a semi-quantitative food-frequency questionnaire and provided fasting serum samples. Comprehensive serum NEFA analysis was performed by multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry. We evaluated the associations of NEFAs using two different reporting methods, with diet quality, specific foods intake, and measures of adiposity and glucose homeostasis., Results: Consistently stronger dietary correlations were observed when expressed as mol%. Serum ω-3 NEFAs were associated with diet quality and fish/fish oil daily servings (DHA mol%, r= 0.37; p = 4.8e-10), and odd-chain NEFAs were associated with full-fat dairy intake (15:0 mol%, r = 0.23; p = 9.0e-5). Glucose intolerance was positively associated with odd chain NEFAs as expressed in µM (r = 0.21; p= 0.001) but inversely associated when expressed as mol% (r = -0.31; p= 2.2e-7). In contrast, monounsaturated NEFAs (µM and mol%) had robust positive associations with pre-pregnancy BMI, second trimester skin-fold thickness, glycated hemoglobin, fasting glucose, and glucose intolerance., Conclusions: This study demonstrates the utility of specific NEFAs and their sub-classes as viable dietary and clinical biomarkers when reported as their relative proportions. More research is needed to investigate inconsistencies between absolute concentrations and relative proportions when reporting fatty acids., (Copyright © 2021. Published by Elsevier Ltd.)

Context: Maternal prepregnancy body mass index (BMI) has a strong influence on gestational metabolism, but detailed metabolic alterations are unknown., Objective: First, to examine the associations of maternal prepregnancy BMI with maternal early-pregnancy metabolite alterations. Second, to identify an early-pregnancy metabolite profile associated with birthweight in women with a higher prepregnancy BMI that improved prediction of birthweight compared to glucose and lipid concentrations., Design, Setting, and Participants: Prepregnancy BMI was obtained in a subgroup of 682 Dutch pregnant women from the Generation R prospective cohort study., Main Outcome Measures: Maternal nonfasting targeted amino acids, nonesterified fatty acid, phospholipid, and carnitine concentrations measured in blood serum at mean gestational age of 12.8 weeks. Birthweight was obtained from medical records., Results: A higher prepregnancy BMI was associated with 72 altered amino acids, nonesterified fatty acid, phospholipid and carnitine concentrations, and 6 metabolite ratios reflecting Krebs cycle, inflammatory, oxidative stress, and lipid metabolic processes (P-values < 0.05). Using penalized regression models, a metabolite profile was selected including 15 metabolites and 4 metabolite ratios based on its association with birthweight in addition to prepregnancy BMI. The adjusted R2 of birthweight was 6.1% for prepregnancy BMI alone, 6.2% after addition of glucose and lipid concentrations, and 12.9% after addition of the metabolite profile., Conclusions: A higher maternal prepregnancy BMI was associated with altered maternal early-pregnancy amino acids, nonesterified fatty acids, phospholipids, and carnitines. Using these metabolites, we identified a maternal metabolite profile that improved prediction of birthweight in women with a higher prepregnancy BMI compared to glucose and lipid concentrations., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Iron deficiency diagnosis is a key health priority during pregnancy. The precise determination of indicators is needed for the evaluation of iron deficiency. In the present study, we investigated the diagnostic features of hepcidin concentration as an iron deficiency assay during the second trimester of pregnancy. We collected 401 venous blood samples of pregnant females from 4 separate birthing hospitals. All the females were within 13-26 weeks of their pregnancy and without any comorbid conditions. The complete blood count, total iron binding capacity, ferritin, serum iron and serum hepcidin were determined. The women were categorized as being non-iron deficient (N-ID), iron deficient (ID), or with iron deficiency anemia (IDA). The mean hepcidin values for examined groups were, i.e., non-iron deficiency was 31.45±4.70 (μg/L), iron deficiency 20.47±2.48 (μg/L) and iron deficiency anemia was 17.33±1.90 (μg/L). The N-ID's hemoglobin mean levels were 13.05±0.10g/dL, ID 12.66±0.05g/dL and the IDA 8.11±00.12g/dL. In this article variations in hepcidin levels between N-ID, ID and IDA women are uncovered and it is reported that the lower hepcidin levels diagnosed in IDA are closely linked to hemoglobin in Pakistani women. Hence it is concluded that hepcidin can be a valuable marker in identifying iron deficiency and iron deficiency anemia during the second trimester of pregnancy, according to the Pearson's correlation data.

Aims/introduction: To examine adverse outcomes in women with early-diagnosed gestational diabetes mellitus using data from a large birth cohort study in Japan., Materials and Methods: This study analyzed data from singleton pregnancies in the Japan Environment and Children's Study including births during 2011-2014. Mothers with an HbA1c level ≥6.5% in the first trimester, a history of diabetes mellitus, or steroid use during pregnancy were excluded. The participants were divided into three groups: control (without gestational diabetes mellitus), early-diagnosed gestational diabetes mellitus (diagnosed before gestational week 24), and late-diagnosed gestational diabetes mellitus (diagnosed after gestational week 24). Multiple logistic regression analysis was performed to calculate the risk of early-diagnosed and late-diagnosed gestational diabetes mellitus for adverse obstetrics outcomes., Results: In total, 100,376 eligible participants were included in this study. The number of individuals in control cases, early-diagnosed gestational diabetes mellitus cases, and late-diagnosed gestational diabetes mellitus cases was 98,090 (97.7%), 751 (0.7%), and 1,535 (1.5%), respectively. When control cases were used as reference, multiple logistic regression analysis revealed that early-diagnosed gestational diabetes mellitus increased the risk of hypertensive disorders of pregnancy (adjusted odds ratio: 2.08, 95% confidence interval: 1.51-2.86), early-onset hypertensive disorders of pregnancy (adjusted odds ratio: 1.91, 95% confidence interval: 1.01-3.65), and late-onset hypertensive disorders of pregnancy (adjusted odds ratio: 1.92, 95% confidence interval: 1.29-2.86)., Conclusion: Early-diagnosed gestational diabetes mellitus is associated with serious obstetric complications. Our findings indicate the necessity of further investigations to validate the benefit of early screening for gestational diabetes mellitus in pregnant women., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: To compare the second-trimester plasma cell-free (PCF) transcriptome of women who delivered at term with that of women with spontaneous preterm birth (sPTB) at or before 32 weeks of gestation and identify/validate PCF RNA markers present by 16 weeks of gestation., Design: Prospective case-control study., Setting: Academic tertiary care centre., Population: Pregnant women with known outcomes prospectively sampled., Methods: PCF RNAs extracted from women at 22-24 weeks of gestation (five sPTB up to 32 weeks and five at term) were hybridised to gene expression arrays. Differentially regulated RNAs for sPTB up to 32 weeks were initially selected based on P value compared with control (P < 0.01) and fold change (≥1.5×). Potential markers were then reordered by narrowness of distribution. Final marker selection was made by searching the Metacore™ database to determine whether the PCF RNAs interacted with a reported set of myometrial Preterm Initiator genes. RNAs were confirmed by quantitative reverse transcription polymerase chain reaction and tested in a second group of 40 women: 20 with sPTB up to 32 weeks (mean gestation 26.5 weeks, standard deviation ±2.6 weeks), 20 with spontaneous term delivery (40.1 ± 0.9 weeks) sampled at 16-19 +5  weeks of gestation., Main Outcome Measure: Identification of PCF RNAs predictive of sPTB up to 32 weeks., Results: Two hundred and ninety-seven PCR RNAs were differentially expressed in sPTB up to 32 weeks of gestation. Further selection retained 99 RNAs (86 mRNAs and 13 microRNAs) and five of these interacted in silica with seven Preterm Initiator genes. Four of five RNAs were confirmed and tested on the validation group. The expression of each confirmed PCF RNA was significantly higher in sPTB up to 32 weeks of gestation. In vitro study of the four mRNAs revealed higher expression in placentas of women with sPTB up to 32 weeks and the potential to interfere with myometrial quiescence., Conclusions: The PCF RNA markers are highly associated with sPTB up to 32 weeks by 16 weeks of gestation., Tweetable Abstract: Women destined for spontaneous preterm birth can be identified by 16 weeks of gestation with a panel of maternal plasma RNAs., (© 2021 John Wiley & Sons Ltd.)

Context: Autism spectrum disorders (ASDs) are a group of conditions characterized by impaired social function and repetitive behaviors. Their etiology is largely unknown., Objective: This work aims to examine the associations of maternal second-trimester and cord blood leptin and adiponectin levels with ASDs in offspring., Methods: We used data from 1164 mother-child pairs enrolled in Project Viva, a prospective prebirth cohort. We used logistic regression analysis to examine the associations of leptin and adiponectin levels in maternal second-trimester blood and cord blood obtained at birth with ASDs. Additionally, we examined the association of maternal prepregnancy body mass index (BMI) as an exposure. Main outcome measures included doctor-diagnosed ASDs reported by mothers using questionnaires in midchildhood and early adolescence., Results: The cumulative incidence of ASDs was 3.4%. Maternal prepregnancy BMI (per 5 points) was positively associated with ASDs in a logistic regression model adjusted for maternal race/ethnicity, education, smoking status and child sex (adjusted odds ratio [OR] 1.38; 95% CI, 1.06-1.79). Higher second-trimester adiponectin was associated with lower odds of ASD in offspring (unadjusted OR 0.49; 95% CI, 0.30-0.78; and OR 0.54; 95% CI, 0.32-0.91 after adjusting for maternal race/ethnicity, education, child sex, OR 0.55; 95% CI, 0.33-0.93 after adjusting for BMI, gestational weight gain, gestational diabetes, and smoking status). Maternal leptin and cord blood leptin and adiponectin levels were not associated with ASDs., Conclusion: Prepregnancy BMI and adiponectin during pregnancy may be useful as a tool to monitor the risk of autism. Increasing adiponectin levels prenatally may play a role in the prevention of ASDs., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study was designed to evaluate the correlation between serum pentraxin-3 (PTX3)/hypersensitivity CRP (hs-CRP) expression and obesity during pregnancy and their application as inflammatory biomarkers in obese pregnant women., Materials and Methods: Pregnant women scheduled to experience a single-birth at our hospital between 2016 and 2017 were selected for this nested case-control study. These patients were evaluated for age and gestational age in the first trimester (11-14 weeks), had their body mass index (BMI) calculated and were subjected to an OGTT between Week 24 and 28 of pregnancy. Obese patients with normal OGTT and a BMI of ≥30 kg/m 2 in the second trimester were selected as the obese group (OBE, n = 80), and non-obese pregnant women with normal OGTT with a BMI of <30 kg/m 2 were selected as the control group (CON, n = 80). ELISA was used to detect the expression of PTX3 and hs-CRP., Results: The expression of both PTX3 and hs-CRP increased in both groups, with increasing gestational age (P < 0.05). However, hs-CRP level in Group OBE was increased, compared to that in the healthy control (P < 0.01), during the second trimester. PTX3 expression was also significantly higher in OBE samples than in the control (P < 0.05), during the third trimester; correlation analysis demonstrated that PTX3 was positively correlated with hs-CRP, BMI, fasting plasma glucose and HOMA-IR., Conclusions: The expression levels of both PTX3 and hs-CRP increased with increasing gestational age, and PTX3 expression was related to BMI, which serves to confirm the inflammatory response in these patients., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background: It is unknown whether early postpartum abnormal glucose metabolism (AGM) in women with previous gestational diabetes mellitus (GDM) is related to their mid-trimester lipid profile. The aim of this study was to characterize the mid-trimester lipid profile of women who experienced GDM and developed into different pathophysiologic subtypes of early postpartum AGM., Methods: A retrospective cohort study of 498 women with history of GDM was conducted. A 75-g oral glucose tolerance test (OGTT) and plasma lipid measurements were performed at 24-28 weeks of gestation and 6-12 weeks of postpartum. Insulin secretion and sensitivity were estimated using early postpartum OGTT-based indices., Results: Women in the mid-trimester dyslipidemia group had higher postpartum 30-min and 2-h plasma glucose, higher postpartum 2-h plasma insulin, higher postpartum triglyceride (TG), higher postpartum low density lipoprotein cholesterol (LDL-c) concentrations, lower postpartum 30-min insulinogenic index (IGI 30 ), lower postpartum insulin sensitivity index (ISI), and lower postpartum disposition index than those in the normal lipid group (all P < 0.05). Abnormal mid-trimester TG and LDL-c concentrations were associated with postpartum AGM (adjusted odds ratio [OR] = 1.786, 95 % confidence interval [CI] = 1.142-2.425; and adjusted OR = 1.621, 95 % CI = 1.323-2.051, respectively; both P < 0.05). AGM women with low IGI 30 and low ISI had higher mid-trimester total cholesterol and LDL-c concentrations, and AGM women with low ISI had higher mid-trimester TG concentrations than women with NGT or other subtypes of AGM (all P < 0.05)., Conclusions: GDM women with abnormal mid-trimester TG and LDL-c were predisposed to early postpartum AGM. Postpartum AGM women who experienced GDM had heterogeneous mid-trimester lipid profile when classified according to their pathophysiologic subtype., (© 2021. The Author(s).)

Aims: To investigate whether second trimester maternal serum screening (2TMSS) biomarkers are associated with cerebral palsy (CP) and identify CP characteristics associated with abnormal biomarker levels., Method: In this retrospective case-control data linkage study, we linked mothers of 129 singleton CP cases from a population register to their 2TMSS records and selected 10 singleton pregnancy controls per case (n = 1290). We compared mean and abnormal levels of alpha-fetoprotein (AFP), beta subunit of human chorionic gonadotrophin (β-hCG), unconjugated estriol (uE3), and inhibin between cases and controls and within CP subgroups., Results: Compared to control pregnancies, CP pregnancies had higher mean levels of AFP (1.10 vs. 1.01 multiple of the population median [MoM], p = 0.01) and inhibin (1.10 vs. 0.98 MoM, p ≤ 0.01). CP pregnancies were 2.5 times more likely to be associated with high levels of AFP (OR 2.52 [95% confidence interval [CI] 1.30, 4.65]; p < 0.01) and 2.6 times for inhibin (OR 2.63 [95% CI 1.37, 4.77]; p < 0.01), and 6.8 times when AFP and inhibin were both elevated (OR 6.75 [95% CI 2.41, 18.94]; p < 0.01). In CP cases, high AFP and high inhibin levels were associated with preterm birth and low birthweight., Interpretation: Abnormal second-trimester biomarker levels suggest abnormal placentation plays a role in the causal pathway of some CP cases., (© 2021 John Wiley & Sons Ltd.)

This retrospective cohort study aimed to determine prevalence of GDM diagnosed before 24 weeks of gestation (early-onset GDM) and evaluate associated risk factors and compare pregnancy outcomes between different GDM status. A total of 1200 pregnant women attending antenatal clinic before 24 weeks of gestation were included. GDM screening was offered during first visit and repeat during 24-28 weeks of gestation, using 50-g GCT and 100-g OGTT. GDM was diagnosed in 110 women (13.9%) and early-onset GDM was found in 57 women (9.2%), which accounted for 65.9% of all GDM. Early-onset GDM had significant lower gestational weight gain and higher rates of preeclampsia, LGA infants, and NICU admission. Independent associated factors for early-onset GDM were age ≥ 30 years (aOR 4.89, 95%CI: 2.08-11.50, p  < .001), and previous GDM (aOR 12.26, 95%CI: 3.86-38.93, p  < .001) while DM in family was the only independent factor for late-onset GDM (aOR 2.53, 95%CI: 1.42-4.51, p  = .002).IMPACT STATEMENT What is already known on this subject? Reported prevalence of early-onset GDM varies between studies, depending on the screening strategy and criteria used. Despite treatment, early-onset GDM has been associated with increased adverse maternal and neonatal outcomes in many previous studies. The risks associated with early-onset GDM and the evidence for benefit of early treatment are still unclear. What do the results of this study add? The results showed that early-onset GDM accounted for majority (65.9%) of all GDM. Despite treatment, early-onset GDM increased risk of preeclampsia, LGA infants, and NICU admission. Independent associated factors for early-onset GDM were age ≥ 30 years, and previous GDM while DM in family was the only independent factor for late-onset GDM. What are the implications of these findings for clinical practice and/or further research? Early GDM screening and intensive management, especially in high-risk women, should be implemented to minimise the risks of adverse outcomes. Further studies are needed to determine appropriate criteria to define early-onset GDM and to identify women at higher risk in different population and settings with different screening strategies. Effective management and approaches for this subgroup of GDM should also be further investigated.

Objectives: Early diagnosis of gestational diabetes can lead to greater optimization of glucose control. We evaluated associations between maternal serum analytes (alpha-fetoprotein [AFP], free beta-human chorionic gonadotropin [beta-hCG], inhibin, and estriol) and the development of gestational diabetes mellitus (GDM)., Methods: This retrospective cohort study identified single-ton pregnancies with available second trimester serum analytes between 2009 and 2017. GDM was identified by ICD-9 and -10 codes. We examined the associations between analyte levels and GDM and to adjust for potential confounders routinely collected during genetic serum screening (maternal age, BMI, and race) using logistic regression. Optimal logistic regression predictive modeling for GDM was then performed using the analyte levels and the above mentioned potential confounders. The performance of the model was assessed by receiver operator curves., Results: Out of 5,709 patients, 660 (11.6%) were diagnosed with GDM. Increasing AFP and estriol were associated with decreasing risk of GDM, aOR 0.76 [95% CI 0.60-0.95] and aOR 0.67 [95% CI 0.50-0.89] respectively. Increasing beta-hCG was associated with a decreasing risk for GDM(aOR 0.84 [95% CI 0.73-0.97]). There was no association with inhibin. The most predictive GDM predictive model included beta-hCG and estriol in addition to the clinical variables of age, BMI, and race (area under the curve (AUC 0.75), buy this was not statistically different than using clinical variables alone (AUC 0.74) (p=0.26)., Conclusions: Increasing second trimester AFP, beta-hCG, and estriol are associated with decreasing risks of GDM, though do not improve the predictive ability for GDM when added to clinical risk factors of age, BMI, and race., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)