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Objectives: To ascertain whether abnormalities in neonatal head circumference and/or body weight are associated with levels of angiogenic/antiangiogenic factors in the maternal and cord blood of pregnancies with a congenital heart defect (CHD) and to assess whether the specific type of CHD influences this association. Methods: This was a multicenter case–control study of women carrying a fetus with major CHD. Recruitment was carried out between June 2010 and July 2018 at four tertiary care hospitals in Spain. Maternal venous blood was drawn at study inclusion and at delivery. Cord blood samples were obtained at birth when possible. Placental growth factor (PlGF), soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and soluble endoglin (sEng) were measured in maternal and cord blood. Biomarker concentrations in the maternal blood were expressed as multiples of the median (MoM). Results: PlGF, sFlt‐1 and sEng levels were measured in the maternal blood in 237 cases with CHD and 260 healthy controls, and in the cord blood in 150 cases and 56 controls. Compared with controls, median PlGF MoM in maternal blood was significantly lower in the CHD group (0.959 vs 1.022; P < 0.0001), while median sFlt‐1/PlGF ratio MoM was significantly higher (1.032 vs 0.974; P = 0.0085) and no difference was observed in sEng MoM (0.981 vs 1.011; P = 0.4673). Levels of sFlt‐1 and sEng were significantly higher in cord blood obtained from fetuses with CHD compared to controls (mean ± standard error of the mean, 447 ± 51 vs 264 ± 20 pg/mL; P = 0.0470 and 8.30 ± 0.92 vs 5.69 ± 0.34 ng/mL; P = 0.0430, respectively). Concentrations of sFlt‐1 and the sFlt‐1/PlGF ratio in the maternal blood at study inclusion were associated negatively with birth weight and head circumference in the CHD group. The type of CHD anomaly (valvular, conotruncal or left ventricular outflow tract obstruction) did not appear to alter these findings. Conclusions: Pregnancies with fetal CHD have an antiangiogenic profile in maternal and cord blood. This imbalance is adversely associated with neonatal head circumference and birth weight. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective To investigate the detection of pathogenic microorganisms in umbilical cord blood and maternal blood from 2012 to 2021, so as to improve the collection of umbilical cord blood and guarantee the safety of umbilical cord blood hematopoietic stem cells (HSC) . Methods Detection results of pathogenic microorganisms of umbilical cord blood and maternal blood among 64 077 cases from Tianjin Cord Blood Bank from 2012 to 2021 were retrospectively analyzed. Results A total of, 2 072 cases (3.23%) were detected positive, among which, 184 cases (0.29%) were positive for aerobic bacteria culture, 1 504 cases (2.34%) were positive for anaerobic bacteria culture, and 384 cases (0.60%) were positive for both aerobic and anaerobic bacteria culture. From 2012 to 2021,the overall positive rate showed a downward trend, with a difference in the positive rate between each year (P 0.05).The reactive rate of HBsAg in maternal blood (1.38%) was higher than that of CMV-IgM(0.29%) , anti-TP(0.13%) and anti-HCV (0.12%) . There were differences in the reactive rates of HBsAg, anti-HCV ,and anti-TP in maternal blood among different years (P0.05). The reactive rates of HBsAg and CMV-IgM detected in maternal blood were significantly higher than those in umbilical cord blood (P0.05). Conclusion The reactive rates of anti-HIV and CMV-IgM in cord blood, and that of anti-HIV in maternal blood are low, but those of anti-TP and anti-HCV in cord blood are relatively high. The reactive rate of HBsAg is high in maternal blood,but with a downward trend,but low in umbilical cord blood due to maternal-infantile transmission blocking. The detection of transfusion transmitted pathogens and bacteria plays a critical role on the safety of umbilical cord blood HSCs. Effective detection of transfusion transmitted pathogens and culture of bacteria are the key to ensure the quality of umbilical cord blood, which can improve the safety of umbilical cord blood HSCs transplantation.

Abstract Infectious preterm birth (PTB) is one of the most important causes of perinatal death. It is difficult to find reliable biomarkers accurate to gestational weeks for infectious PTB prediction clinically. Infectious PTB is found usually accompanied with immune imbalance. Thus, the systematic study to find the priority of inflammatory biomarkers and innovative inflammatory clusters for infectious PTB prediction is urgently needed. This systematic study that focused on the inflammatory clusters and infectious PTB in the PubMed database was analyzed by using the criteria of the Population, Intervention, Comparison, Outcome, and Study design (PICOS) framework according to the recommendations of preferred reporting items for systematic reviews and meta-analysis (PRISMA). The network meta-analyzed results showed that the prioritization of the inflammatory factors for infectious PTB prediction is soluble tumor necrosis factor receptor 2 (sTNFR2) > tumor necrosis factor α (TNFα) > interleukin-10 (IL-10) > interleukin-6 (IL-6) > C-reactive protein (CRP) > interleukin-1β (IL-1β). Furthermore, the results also indicated that global consideration of multiple inflammatory factors, such as CRP/IL-1β/IL-6 biomarker cluster in gestational 27–34 weeks, and the tumor necrosis factor/nerve growth factor (TNF/NGF) family during gestational 25–33 weeks, were potential biomarker clusters that specific for infectious PTB prediction. This study systematically pointed out prioritization of the inflammatory factors for infectious PTB prediction. The results also provided evidence that maternal inflammatory clusters can predict infectious PTB occurrence at accurate gestational week. The global consideration of multiple inflammatory factors at accurate gestational age is highlighted.

Abstract Objective: To assess the maternal blood levels of fatty acids (FAs) in pregnancies with fetal growth restriction (FGR). Methods: This prospective cross-sectional study included pregnant women with gestational age between 26 and 37 + 6 weeks with FGR and appropriate for gestational age (AGA) fetuses. The levels of saturated, trans, monounsaturated, and polyunsaturated FAs were measured using centrifugation and liquid chromatography. The Student’s t-test, Mann-Whitney test, and general linear model, with gestational age and maternal weight as covariants, were used to compare FA levels and the FGR and AGA groups. The Chi-square was used to evaluate the association between groups and studied variables. Results: Maternal blood sample was collected from 64 pregnant women, being 24 FGR and 40 AGA. A weak positive correlation was found between the palmitoleic acid level and maternal weight (r = 0.285, p = 0.036). A weak negative correlation was found between the gamma-linoleic acid level and gestational age (r = −0.277, p = 0.026). The median of the elaidic acid level (2.3 vs. 4.7ng/ml, p = 0.045) and gamma-linoleic acid (6.3 vs. 6.6ng/ml, p = 0.024) was significantly lower in the FGR than the AGA group. The palmitoleic acid level was significantly higher in the FGR than AGA group (50.5 vs. 47.6ng/ml, p = 0.033). Conclusion: Pregnant women with FGR had lower elaidic acid and gamma-linoleic acid levels and higher palmitoleic acid levels than AGA fetuses.

Pregnancy requires a high demand of energy, which leads to an increase of oxidative stress. The aim of this study was to assess the oxidative status in 200 couples of pregnant women-newborns at the time of delivery, for the first time, who gave birth in two University Hospitals from the province of Seville. Recruited women filled an epidemiological questionnaire with their demographic characteristics and dietary habits during pregnancy. At the time of delivery, both maternal and cord blood samples were collected. Protein oxidation, superoxide dismutase, and catalase levels were measured to assess the oxidative status of these women, together with the levels of vitamins D, B12, Zn, Se, and Cu. Our results showed a tendency for all biomarkers measured to be higher in cord blood than in maternal blood. For the correlations established between the OS markers and sociodemographic characteristics, only significant differences for carbonyl groups values were found on both maternal and cord blood, relating these higher values to the use of insecticides in the women's homes. For newborns, only a significant correlation was detected between antioxidant enzymes and the newborn's weight, specifically for superoxide dismutase activity. Additionally, the higher values obtained in cord blood might suggest metabolization, while a higher production of ROS and antioxidant enzymes might be required to maintain the balance. Measured levels for Se were similar in both maternal and cord blood, unlike Cu and Zn, where higher levels were found for maternal blood than cord blood, indicating a correlation between maternal Se values and SOD as OS biomarker. Furthermore, vitamin D levels were around the optimum values established, finding a relationship between vitamin D and new-born's height, unlike for vitamin B12 values, where a correlation with maternal food consumption characteristics was established. Overall values were inside normal ranges and consistent for our population. [Display omitted] • Blood samples were drawn at delivery to study the maternal and offspring oxidative status. • All biomarkers measured were slightly higher in cord blood than in maternal blood. • The strongest positive correlation was observed in catalase in the Aljarafe cohort. • Carbonyl groups values on maternal and cord blood were found related with home use of insecticides. • Antioxidant enzymes and newborn's weight led to a significant correlation. [ABSTRACT FROM AUTHOR]

Our proof-of-concept study develops a suspect screening workflow to identify and prioritize potentially ubiquitous chemical exposures in matched maternal/cord blood samples, a critical period of development for future health risks. We applied liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF/MS) to perform suspect screening for ∼3500 industrial chemicals on pilot data from 30 paired maternal and cord serum samples (n = 60). We matched 662 suspect features in positive ionization mode and 788 in negative ionization mode (557 unique formulas overall) to compounds in our database, and selected 208 of these for fragmentation analysis based on detection frequency, correlation in feature intensity between maternal and cord samples, and peak area differences by demographic characteristics. We tentatively identified 73 suspects through fragmentation spectra matching and confirmed 17 chemical features (15 unique compounds) using analytical standards. We tentatively identified 55 compounds not previously reported in the literature, the majority which have limited to no information about their sources or uses. Examples include (i) 1-(1-acetyl-2,2,6,6-tetramethylpiperidin-4-yl)-3-dodecylpyrrolidine-2,5-dione (known high production volume chemical) (ii) methyl perfluoroundecanoate and 2-perfluorooctyl ethanoic acid (two PFAS compounds); and (iii) Sumilizer GA 80 (plasticizer). Thus, our workflow demonstrates an approach to evaluating the chemical exposome to identify and prioritize chemical exposures during a critical period of development.

The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non-typical development (Non-TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one-carbon metabolites, on gene pathways and neurodevelopment. Genome-wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies-Learning Early Signs. Sixteen different one-carbon metabolites, including folic acid, betaine, 5'-methyltretrahydrofolate (5-MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non-TD and ASD, and to one-carbon metabolites. Using differential gene expression analysis, six transcripts (TGR-AS1, SQSTM1, HLA-C, and RFESD) were associated with child outcomes (ASD, Non-TD, and TD) with genome-wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co-expressed gene modules significantly correlated with 5-MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5-MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co-expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one-carbon metabolite status and changes relevant to children's later neurodevelopmental outcomes. LAY SUMMARY: Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non-typical neurodevelopment and were associated with maternal nutrients.

This study aims to explore the relationship between macrosomia and amino acids in maternal and cord sera. Methods: In the case-control study, 78 pairs of mothers and newborns were recruited from December 2016 to November 2019. Participants were divided into the macrosomia group (BW ≥ 4000 g, n = 39) and the control group (BW between 2500 g and 3999 g, n = 39) according to the birth weight (BW) of newborns. Maternal vein blood samples were collected before delivery and cord vein blood samples were collected after birth. The levels of amino acids in maternal and cord sera were measured by liquid chromatography and mass spectrometry (LC-MS/MS) in the year 2021. The difference in amino acid levels in maternal and cord sera between the two groups was compared, and the contribution of each amino acid to the difference between the two groups was analyzed. Unconditional logistic regression analysis was used to test the relationship between macrosomia and amino acids. Results: In maternal serum during the antepartum, the levels of asparagine, glutamine, methionine, alanine, and threonine in the macrosomia group were higher but arginine was lower than that in the control group (p < 0.05). In cord serum, the levels of lysine, histidine, phenylalanine, arginine, tryptophan, valine, isoleucine, glutamate, tyrosine, and total essential amino acid (EAA) in the macrosomia group were lower while glutamine was higher than that in the control group (p < 0.05). The ratios of EAA, valine, threonine, methionine, tryptophan, and alanine in maternal serum to those in cord serum were higher, while the ratio of glutamine was lower in the macrosomia group (p < 0.05). Arginine and threonine in maternal serum and glutamate, glutamine, and histidine in cord serum were associated with macrosomia (p < 0.05). Conclusion: Most of the amino acid levels in the maternal sera of the macrosomia group are higher than those in the control group, while most of the amino acids' levels in the cord sera of the macrosomia group are lower than those in the control group. The ratios of some amino acids in maternal serum to those in cord serum were different between the two groups. Arginine and threonine in maternal serum and glutamate, glutamine, and histidine in cord serum are closely related to macrosomia. [ABSTRACT FROM AUTHOR]

Infectious preterm birth (PTB) is one of the most important causes of perinatal death. It is difficult to find reliable biomarkers accurate to gestational weeks for infectious PTB prediction clinically. Infectious PTB is found usually accompanied with immune imbalance. Thus, the systematic study to find the priority of inflammatory biomarkers and innovative inflammatory clusters for infectious PTB prediction is urgently needed. This systematic study that focused on the inflammatory clusters and infectious PTB in the PubMed database was analyzed by using the criteria of the Population, Intervention, Comparison, Outcome, and Study design (PICOS) framework according to the recommendations of preferred reporting items for systematic reviews and meta-analysis (PRISMA). The network meta-analyzed results showed that the prioritization of the inflammatory factors for infectious PTB prediction is soluble tumor necrosis factor receptor 2 (sTNFR2) > tumor necrosis factor α (TNFα) > interleukin-10 (IL-10) > interleukin-6 (IL-6) > C-reactive protein (CRP) > interleukin-1β (IL-1β). Furthermore, the results also indicated that global consideration of multiple inflammatory factors, such as CRP/IL-1β/IL-6 biomarker cluster in gestational 27–34 weeks, and the tumor necrosis factor/nerve growth factor (TNF/NGF) family during gestational 25–33 weeks, were potential biomarker clusters that specific for infectious PTB prediction. This study systematically pointed out prioritization of the inflammatory factors for infectious PTB prediction. The results also provided evidence that maternal inflammatory clusters can predict infectious PTB occurrence at accurate gestational week. The global consideration of multiple inflammatory factors at accurate gestational age is highlighted. [ABSTRACT FROM AUTHOR]

Xudong Dong,1,2,&ast; Ailing Ding,2,&ast; Hong Hu,1 Fanping Xu,1 Lingyan Liu,1 Min Wu1,3 1The Obstetrical Department of the First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650500, People’s Republic of China; 2Faculty of Life Science and Technology, Kunming University of Science & Technology, Kunming, 650500, People’s Republic of China; 3Yunnan Provincial Key Laboratory of Carbon Sequestration and Pollution Control in Soils, Faculty of Environmental Science & Engineering, Kunming University of Science & Technology, Kunming, 650500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Wu, Email minwupp@163.comPurpose: As two of the most severe and common medical disorders during pregnancy, gestational diabetes mellitus (GDM) and hypertensive disorder complicating pregnancy (HDCP) cause adverse effects on placental barrier function and thus may lead to a high risk of intrauterine exposure to toxic metals from mother to fetus. This study investigates the impact of the placental barrier on the transfer of cadmium (Cd) from mother to fetus and the relationship between pregnancy complications.Methods: A total of 107 pairs of samples were collected in Kunming, China; 29 were from healthy pregnant women, and 78 were from patients with pregnancy complications. Cd was measured in each mother’s placenta and maternal and umbilical cord blood. The expressions of MT and Cd-MT complex in blood and placental tissue samples were determined by enzyme-linked immunosorbent assay (ELISA).Results: The cesarean section rate in the whole pathological group (60.7%) was higher than that in the normal group (20.7%), and the ratio of the effective barrier (ratio of maternal blood to umbilical cord blood> 1) in the pathological group (74%) was lower than that in the normal group (79%). In addition, the proportion of practical placental barriers in women aged 20– 25 years was 83.3%, 76.3% in women aged 26– 30 years, 74.3% in women aged 31– 35 years, 70% in women aged 36– 40 years, and 71% in women aged 40– 45 years. The Cd content in the placenta of the three pathological groups was significantly higher than that in maternal and umbilical cord blood (P< 0.05), and the distribution of Cd was the same as that in the normal group. However, there was no significant difference between maternal and umbilical cord blood Cd concentrations in the pathological group. The Cd concentration in the normal group’s maternal blood was significantly higher than that in cord blood (P< 0.05). In addition, the expression levels of both metallothionein (MT) and Cd-MT complex in placenta is much higher than in maternal and umbilical blood, and which in normal group are significantly higher than those in pathological group.Conclusion: Both mothers and fetuses are at increased health risk for pregnancy disorders when maternal age, BMI, or body weight increases. Increased maternal age increases the likelihood of Cd transfer from the mother to the fetus. Pregnancy complications may induce lower expression of MT, thus reducing the Cd-MT complex in the placenta, weakening the placental barrier, and increasing the risk of Cd transfer and exposure to the fetus.Keywords: gestational diabetes mellitus, gestational hypertension, maternal blood, placenta barrier, pregnancy complication

It is now well established that maternal serum markers are often abnormal in fetal trisomy 21. Their determination is recommended for prenatal screening and pregnancy follow-up. However, mechanisms leading to abnormal maternal serum levels of such markers are still debated. Our objective was to help clinicians and scientists unravel the pathophysiology of these markers via a review of the main studies published in this field, both in vivo and in vitro, focusing on the six most widely used markers (hCG, its free subunit hCGβ, PAPP-A, AFP, uE3, and inhibin A) as well as cell-free feto–placental DNA. Analysis of the literature shows that mechanisms underlying each marker's regulation are multiple and not necessarily directly linked with the supernumerary chromosome 21. The crucial involvement of the placenta is also highlighted, which could be defective in one or several of its functions (turnover and apoptosis, endocrine production, and feto–maternal exchanges and transfer). These defects were neither constant nor specific for trisomy 21, and might be more or less pronounced, reflecting a high variability in placental immaturity and alteration. This explains why maternal serum markers can lack both specificity and sensitivity, and are thus restricted to screening. [ABSTRACT FROM AUTHOR]

Objective To analyze the diagnostic value of T cell immunoglobulin mucin molecule-3 (TIM-3) and GATA binding protein-3 (GATA-3) in maternal blood and amniotic fluid in the diagnosis of premature rupture of membranes (PROM) complicated with intrauterine infection. Methods Eighty-nine patients with PROM were regarded as the research subjects. Among them, 42 patients with intrauterine infection were regarded as the infection group, and 47 patients without intrauterine infection were regarded as the uninfected group. Meantime, 45 normal full-term pregnant women were used as the control group. According to the severity of intrauterine infection, PROM complicated with intrauterine infection patients were divided into the mild group (16 cases), the moderate group (17 cases) and the severe group (9 cases). The mRNA and protein levels of TIM-3, GATA-3 in whole blood and amniotic fluid were detected. The mRNA and protein levels of TIM-3, GATA-3 in whole blood and amniotic fluid were compared between the control group, the uninfected group, the infection group and pregnant women with different degrees of infection. The efficacy of TIM-3 and GATA-3 proteins in serum and amniotic fluid alone and in combination in the diagnosis of intrauterine infection in pregnant women with PROM were analyzed by receiver operating characteristic curve. Results The TIM-3 mRNA and protein levels in whole blood and amniotic fluid of the control group, the uninfected group and the infection group were increased in turn (P＜0.05), and GATA-3 mRNA and protein levels decreased in turn (P＜0.05). The TIM-3 mRNA and protein levels in whole blood and amniotic fluid of the mild group, the moderate group and the severe group increased in turn (P＜0.05), and GATA-3 mRNA and protein levels decreased in turn (P＜0.05). The area under curve of serum TIM-3 and GATA-3 protein alone and in combination, and amniotic fluid TIM-3 and GATA-3 protein alone and in combination to diagnose intrauterine infection in pregnant women with PROM were 0.854, 0.813, 0.937, 0.834, 0.850 and 0.922, respectively. Conclusion The maternal blood and amniotic fluid of patients with PROM complicated with intrauterine infection have high expression of TIM-3 and low expression of GATA-3, both of them have certain diagnostic value for intrauterine infection in pregnant women with PROM, and the combined diagnostic efficiency is higher. [ABSTRACT FROM AUTHOR]

Neonicotinoid pesticides (NNs) have been reported to have neurobehavioral effects on offspring after fetal and lactational exposure. In this study, clothianidin (CLO), an NN, was administered orally as a single dose (6.5 mg/kg: 1/10 of the no-observed-adverse-effect level in the current Pesticide Evaluation Report) to 10-day post-partum ICR mice, and CLO and its metabolites desmethyl-CLO (dm-CLO) were quantified using liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI/MS/MS) after collecting maternal breast milk and blood samples over time (1, 3, 6, 9, 12, and 24 h after administration). CLO and dm-CLO were detected in the breast milk at 1 h after the administration, and their concentrations were significantly higher than those in blood at all time points. The concentrations of CLO and dm-CLO in the breast milk were at their highest levels at 1 and 3 h, respectively, and then decreased over time to become almost undetectable at 24 h after the administration. These results show that CLO is metabolized in the mother's body and is rapidly transferred to and concentrated in the breast milk. Since CLO concentrations in breast milk are higher than those in the blood, there is concern about the effects of CLO during lactation. • CLO is metabolized maternally in mice and rapidly transferred in breast milk. • CLO and metabolites are more highly concentrated in breast milk than maternal blood. • Most of CLO and its metabolites were eliminated from the mother's body within 24 h. • Infants are sensitive to chemicals, so adverse CLO effects in infants are a concern. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyse the association between stannum exposure during pregnancy and congenital heart diseases in offspring. Based on a prospective birth cohort study conducted in Gansu Maternal and Child Health Hospital from 2010 to 2012, 14,359 pregnant women were followed up using a nested case-control study method. 97 pregnant women whose offspring were diagnosed with CHDs were used as the case group, and 194 pregnant women whose offspring did not suffer from congenital heart diseases were used as the control group in a ratio of 1:2 according to their age and place of birth. Inductively coupled plasma mass spectrometry was used to determine elemental stannum in blood samples from pregnant women hospitalized for delivery and in fetal cord blood samples. Multifactorial logistic regression analysis was used to assess the association between stannum and offspring CHDs. There was a moderate positive correlation between the concentration of stannum in pregnant women's blood and that in umbilical cord blood. A higher concentrations of maternal blood stannum level was associated with a greater risk of CHDs (aOR 3.409, 95%CI 1.785–6.826), isolated CHDs (aOR 4.044, 95%CI 1.803–9.070), multiple CHDs (aOR 2.625, 95%CI 1.137–6.061), patent ductus arteriosus (aOR 2.882, 95%CI 1.443–5.756), atrial septal defects (aOR 3.067, 95%CI 1.406–6.690), ventricular septal defects (aOR 7.414, 95%CI 1.414–38.874). There was a correlation between the maternal and cord blood sample suggesting stannum crosses the placenta. • This article is the first to present the relationship between heavy metal tin exposure during pregnancy and congenital heart diseases. • Informing the prevention of CHD and the development of public health interventions. • First simultaneous analysis of maternal blood tin exposure and cord blood tin exposure in relation to congenital heart diseases. [ABSTRACT FROM AUTHOR]

Hepcidin is a primary regulator of iron metabolism in the human body. By promoting ferroportin degradation, hepcidin reduces intestinal iron absorption and its release from intracellular stores. In the course of pregnancy, gradually declining hepcidin concentrations encourage placental iron transfer, thereby providing the appropriate amount of iron for fetal development. Hence, we aimed to investigate changes in maternal and cord blood hepcidin and iron metabolism parameters in normal-weight (n=17) and obese (n=17) gestating women, as well as gravid women with a history of hypothyroidism following the restoration of euthyroidism (n=17). All blood samples were taken on the day of delivery, and ELISA kits were used for measurements. A significant increase in maternal hepcidin concentration was observed in obese pregnant women, compared to normal-weight controls (29.53±4.20 ng/mL vs. 25.69±5.70 ng/mL; P<0.05). However, only a slight, insignificant tendency for lower hepcidin was noted in the hypothyroid group, compared to the healthy controls (23.10±6.00 ng/mL vs. 25.69±5.70 ng/mL; P=NS). Moreover, decreased maternal free triiodothyronine, triiodothyronine, free thyroxine, and ferritin levels were revealed in the hypothyroid group, compared to the normalweight individuals (P<0.05). Furthermore, positive correlations between maternal hepcidin and the majority of maternal thyroid hormones were found, with a most potent relation to FT3 (r=0.40; P<0.01). Interestingly, no alterations of thyroid hormones and iron metabolism parameters were noticed in cord blood in any of the subgroups. In summary, prepregnancy obesity is associated with elevated maternal hepcidin, albeit no signs of lowered cord blood iron status were shown. Medical history of hypothyroidism following the restoration of euthyroidism does not substantially influence maternal nor cord blood hepcidin concentration, as well as fetal iron homeostasis, even though free thyroid hormone levels correlate with maternal hepcidin. [ABSTRACT FROM AUTHOR]

This study aims to explore the relationship between macrosomia and amino acids in maternal and cord sera. Methods: In the case-control study, 78 pairs of mothers and newborns were recruited from December 2016 to November 2019. Participants were divided into the macrosomia group (BW ≥ 4000 g, n = 39) and the control group (BW between 2500 g and 3999 g, n = 39) according to the birth weight (BW) of newborns. Maternal vein blood samples were collected before delivery and cord vein blood samples were collected after birth. The levels of amino acids in maternal and cord sera were measured by liquid chromatography and mass spectrometry (LC-MS/MS) in the year 2021. The difference in amino acid levels in maternal and cord sera between the two groups was compared, and the contribution of each amino acid to the difference between the two groups was analyzed. Unconditional logistic regression analysis was used to test the relationship between macrosomia and amino acids. Results: In maternal serum during the antepartum, the levels of asparagine, glutamine, methionine, alanine, and threonine in the macrosomia group were higher but arginine was lower than that in the control group (p < 0.05). In cord serum, the levels of lysine, histidine, phenylalanine, arginine, tryptophan, valine, isoleucine, glutamate, tyrosine, and total essential amino acid (EAA) in the macrosomia group were lower while glutamine was higher than that in the control group (p < 0.05). The ratios of EAA, valine, threonine, methionine, tryptophan, and alanine in maternal serum to those in cord serum were higher, while the ratio of glutamine was lower in the macrosomia group (p < 0.05). Arginine and threonine in maternal serum and glutamate, glutamine, and histidine in cord serum were associated with macrosomia (p < 0.05). Conclusion: Most of the amino acid levels in the maternal sera of the macrosomia group are higher than those in the control group, while most of the amino acids’ levels in the cord sera of the macrosomia group are lower than those in the control group. The ratios of some amino acids in maternal serum to those in cord serum were different between the two groups. Arginine and threonine in maternal serum and glutamate, glutamine, and histidine in cord serum are closely related to macrosomia.

Abstract Background Preterm birth, defined as parturition before 37 completed weeks of gestation, is associated with an increased risk of neonatal complications and death, as well as poor health and disease later in life. Epigenetics could contribute to the mechanism underlying preterm birth. Results Genome-wide DNA methylation analysis of whole blood cells from 10 women (5 term and 5 preterm deliveries) was performed using an Illumina Infinium HumanMethylation450 BeadChips array. We identified 1,581 differentially methylated CpG sites in promoter regions between term and preterm birth. Although the differences were not significant after correcting for multiple tests, seven CpGs on the genomically imprinted vault RNA2-1 (VTRNA2-1; also known as non-coding RNA, nc886 or miR-886) showed the largest differences (range: 26–39 %). Pyrosequencing verification was performed with blood samples from pregnant women recruited additionally (39 term and 43 preterm deliveries). In total, 28 (34.1 %) samples showed hypomethylation of the VTRNA2-1 promoter (

Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is involved in the production of fetal lung surfactant. We have shown that LPCAT1 mRNA is present in amniotic fluid and maternal plasma and that its quantity correlates with the amniotic fluid lamellar body count. The purpose of the present study was to assay maternal plasma for the LPCAT1 protein in term and preterm pregnancies; and to measure the impact of antenatal corticosteroids. Maternal and newborn plasma samples were obtained from 7 women admitted to the hospital for induction of labor. Maternal plasma was also obtained before administration of corticosteroids and 24 h after the second dose of corticosteroids from 12 women with premature labor and premature rupture of membranes. After sample preparation, LPCAT1 protein levels were determined using sandwich ELISA. We discovered LPCAT1 protein in maternal plasma in measurable quantities after 32 weeks gestation. Further, there was a rise of maternal plasma LPCAT1 in response to the clinical administration of antenatal corticosteroids. Quantitation of maternal plasma LPCAT1 protein offers promise in the ongoing study of fetal lung maturation. [ABSTRACT FROM AUTHOR]

BackgroundPrevious studies have found that exposure to heavy metals increased the incidence of congenital heart defects (CHDs). However, there is a paucity of information about the connection between exposure to titanium and CHDs. This study sought to examine the relationship between prenatal titanium exposure and the risk of CHDs in offspring.MethodsWe looked back on a birth cohort study that was carried out in our hospital between 2010 and 2012. The associations between titanium exposure and the risk of CHDs were analyzed by using logistic regression analysis to investigate titanium concentrations in maternal whole blood and fetal umbilical cord blood.ResultsA total of 97 case groups and 194 control groups were included for a nested case-control study. The [P50 (P25, P75)] of titanium were 371.91 (188.85, 659.15) μg/L and 370.43 (264.86, 459.76) μg/L in serum titanium levels in pregnant women and in umbilical cord serum titanium content in the CHDs group, respectively. There was a moderate positive correlation between the concentration of titanium in pregnant women's blood and that in umbilical cord blood. A higher concentrations of maternal blood titanium level was associated with a greater risk of CHDs (OR 2.706, 95% CI 1.547–4.734), the multiple CHDs (OR 2.382, 95% CI 1.219–4.655), atrial septal defects (OR 2.367, 95% CI 1.215–4.609), and patent ductus arteriosus (OR 2.412, 95% CI 1.336–4.357). Dramatically higher concentrations of umbilical cord blood levels had an increased risk of CHDs and different heart defects.ConclusionTitanium can cross the placental barrier and the occurrence of CHDs may be related to titanium exposure.

Overweight/obesity is the main risk factor for gestational diabetes mellitus (GDM). In our cohort of pregnant women with GDM, n = 19, and without, n = 22, we previously reported a significant increase in SOCS3 mRNA expression (+62%) in visceral adipose tissue (VAT) according to GDM, without altered promoter DNA-methylation. Here, we examined methylation status of additional SOCS3 exon 2 regions in VAT and maternal blood. We found significantly altered methylation at specific CpG sites corresponding to aberrant mRNA expression levels of SOCS3 in VAT. We propose a potential regulatory element/region within exon 2; however, this region does not appear to be a good blood-marker representing VAT.

The effects of prenatal element exposure on mothers and fetuses have generated concern. Profiles of trace and toxic elements in biological material are urgently desired, especially for women who reside near e-waste recycling facilities. The aim of this study was to investigate elements concentrations in placenta, cord blood, and maternal blood of women and to evaluate the influencing factors. A group of 48 women from an e-waste recycling site and a group of 31 women from a non-e-waste recycling site were recruited. Basic characteristics were collected by questionnaire and the concentrations of 17 elements in placenta, cord blood, and maternal blood samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Finally, the generalized linear model regression analysis (GLM) was used to test the association between element concentrations and possible factors. Compared to the control group, the exposed group had significantly elevated cadmium (Cd), zinc (Zn), nickel (Ni), and antimony (Sb) in placenta, and higher lead (Pb) in maternal blood and cord blood (P<0.05). Sb concentration in maternal blood was significantly lower than in the control group (P <0.05). GLM analysis showed that element concentrations were mainly associated with maternal age [chromium (Cr), iron (Fe), selenium (Se), cobalt (Co), mercury (Hg) in placenta, copper (Cu) in maternal blood], education (Se, Sb in placenta), family income (Cu in maternal blood and Ni in placenta), passive smoking [Cu and Zn in placenta, Pb in maternal blood], and e-waste contact history (Hg in cord blood, Cu, Zn, and Cd in maternal blood). Women in the e-waste recycling area had higher toxic element levels in the placenta and blood samples. More preventive measures were needed to reduce the risk of element exposure for mothers and fetuses in these areas. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: About 30% of women entering pregnancy in the US are obese. We have previously reported mitochondrial dysregulation and increased inflammation in the placentae of obese women. Vitamin D (VitD) is a major player in calcium uptake and was shown to modulate mitochondrial respiration and the immune/inflammation system. Studies show decreased VitD levels in obese individuals; however, the effect of maternal obesity on VitD metabolism and its association with placental function remains understudied. Methods: Maternal and cord blood plasma and placental samples were collected upon C-section from normal-weight (NW, body mass index [BMI]<25) and obese (OB, BMI>30) women with uncomplicated pregnancies at term. We measured 25(OH)D3 (calcidiol) levels in maternal and cord blood plasma using ELISA. We assessed the expression of CYP27B1, an activator of calcidiol, and Vitamin D receptor (VDR) in placentae from NW and OB, and women with gestational diabetes and preeclampsia. In addition, we examined the effects of VitD supplementation on mitochondrial function and inflammation in trophoblasts from NW and OB, using the Seahorse Bioanalyzer and Western blot, respectively. Results: Vitamin D levels in blood from OB but not NW women and in cord blood from babies born to NW and OB women showed a significant inverse correlation with maternal pre-pregnancy BMI (r=-0.50, p <0.1 and r=-0.55, p =0.004 respectively). Cord plasma VitD levels showed a positive correlation with placental efficiency, i.e., the ratio between fetal and placental weight, as well as with maternal blood VitD levels (r=0.69 and 0.83 respectively, p <0.00). While we found no changes in CYP27B1 in OB vs. NW women, VDR expression were decreased by 50% (p <0.03) independent of fetal sex. No changes in VDR expression relative to BMI-matched controls were observed in the placentae of women with gestational diabetes or preeclampsia. Cytotrophoblasts isolated from placentae of OB women showed a dose-dependent increase in VDR expression after 24-hour treatment with calcitriol (10 nM and 100 nM), an active form of VitD. Trophoblasts isolated from OB women and treated with calcitriol improved mitochondrial respiration (p <0.05). We also found a two-fold increase in expression of the NLRP3 inflammasome and the pro-inflammatory cytokine IL-18 in trophoblasts isolated from placentae of OB women (p <0.05), with IL-18 expression being reversed by calcitriol treatment (100 nM). Conclusions: We show that VitD deficiency is at least partially responsible for mitochondrial dysfunction and increased inflammation in the placentae of obese women. Vitamin D supplementation could be beneficial in improving placental dysfunction seen in obese women. [ABSTRACT FROM AUTHOR]

To develop an appropriate sampling strategy to assess the intrauterine exposure to dechlorane plus (DP), we investigated DP levels in sequential maternal blood samples collected in three trimesters of pregnancy, respectively, from women living in Taizhou. The median concentration of DPs (sum of syn-DP and anti-DP) in all samples was 30.5 pg g−1 wet-weight and 5.01 ng g−1 lipid-adjusted weight, respectively. The trimester-related DP concentrations were consistently strongly correlated (p < 0.01), indicating that a single measurement of DP levels could represent intrauterine exposure without sampling from the same female repeatedly; however, the wet-weight levels significantly increased across trimesters (p < 0.05), while the lipid-adjusted levels did not significantly vary. Notably, whether lipid-adjusted weight or wet-weight levels, the variation extent of DP across trimesters was found to be less than 41%, and those for other persistent organic pollutants (POPs) reported in the literature were also limited to 100%. The limitation in variation extents indicated that, regardless of the time of blood collection during pregnancy and how the levels were expressed, a single measurement could be extended to screen for exposure risk if necessary. Our study provides different strategies for sampling the maternal blood to serve the requirement for assessment of in utero exposure to DP. [ABSTRACT FROM AUTHOR]

Maternal obesity and excessive gestational weight gain (EGWG) may have persistent effects on offspring obesity and be risk factors for both mother and child. Studies have reported that asprosin concentration is associated with metabolism and weight changes during pregnancy. This study therefore evaluated the association of maternal and newborn asprosin with normal weight gain and EGWG and nutritional intake in pregnancy. The study included 30 pregnant women with normal weight gain and 30 women with EGWG referred to Ali ibn Abi Talib Hospital in Zahedan, Iran, September 2020 to June 2021. A demographic questionnaire and neonatal complications checklist were completed. Asprosin concentrations at the time of delivery in maternal venous blood samples and umbilical vein blood samples were measured by ELISA technique. Macronutrient and energy intake were assessed by a 24‐h dietary recall questionnaire and compared with standard Recommended Dietary Allowance (RDA) and Dietary References Intake (DRI) values. Asprosin levels were significantly higher in the EGWG group's umbilical cord blood than in the control group but there was no difference in maternal asprosin concentrations between the two groups. The Appearance, Pulse, Grimace, Activity and Respiration (Apgar) score was significantly lower in the EGWG group than in the control group, although there was no difference in birthweight between the groups. Weight gain during pregnancy, energy intake and protein and carbohydrate consumption were significantly higher in the EGWG group than in the control group (p < 0.05). It seems that differences in asprosin secretion do not mediate an imbalance in energy intake and other macronutrients during pregnancy that affect pregnancy weight gain and birthweight. However, excessive gestational weight gain was associated with neonatal asprosin levels and newborn Apgar scores. [ABSTRACT FROM AUTHOR]

Placenta accreta spectrum (PAS) refers to the abnormal invasion of trophoblastic tissues. Because of its increasing morbidity and possibility of catastrophic outcomes, PAS requires an antenatal diagnosis and making full preparations in advance to realize safe delivery. Current clinical screening modalities for PAS are not always conclusive. Recently, it has been reported that bio-markers detected in maternal serum have the potential for predicting PAS during pregnancy. Some of these biomarkers, such as β-hcg, AFP, PAPP-A, and cffDNA, can be clinically detected. It is convenient for us to test and compare with standard threshold. However, how can we distinguishing PAS from other pregnancy complications through these biomarkers remains complicated. Some biomarkers are specific, such as microRNA and placenta-specific mRNA. They are stability and reliability. These biomarkers are currently research hotspots. This study aims to summarize the characteristics of the newly reported biomarkers and to point out their potential application and current limitations to provide a basis for future research. Finally, the combination of imageological examination and biomarkers will be an attractive future theme to study in diagnosing this challenging condition.

BackgroundAbout 30% of women entering pregnancy in the US are obese. We have previously reported mitochondrial dysregulation and increased inflammation in the placentae of obese women. Vitamin D (VitD) is a major player in calcium uptake and was shown to modulate mitochondrial respiration and the immune/inflammation system. Studies show decreased VitD levels in obese individuals; however, the effect of maternal obesity on VitD metabolism and its association with placental function remains understudied.MethodsMaternal and cord blood plasma and placental samples were collected upon C-section from normal-weight (NW, body mass index [BMI]30) women with uncomplicated pregnancies at term. We measured 25(OH)D3 (calcidiol) levels in maternal and cord blood plasma using ELISA. We assessed the expression of CYP27B1, an activator of calcidiol, and Vitamin D receptor (VDR) in placentae from NW and OB, and women with gestational diabetes and preeclampsia. In addition, we examined the effects of VitD supplementation on mitochondrial function and inflammation in trophoblasts from NW and OB, using the Seahorse Bioanalyzer and Western blot, respectively.ResultsVitamin D levels in blood from OB but not NW women and in cord blood from babies born to NW and OB women showed a significant inverse correlation with maternal pre-pregnancy BMI (r=-0.50, p

Hormone secretion by the maternal ovaries, trophoblast/placenta and fetus occurs sequentially, creating distinct steroid metabolomic 'signatures' in systemic blood of pregnant mares that vary with gestational stage. Algorithms were developed to predict the gestational day (GD) from the maternal steroid metabolome (nine steroids; pregnenolone (P5), progesterone (P4), 5a-dihydroprogesterone (DHP), 17a-hydroxyprogesterone, allopregnanolone, 20a-hydroxy-DHP, 3ß,20a-dihydroxy-DHP, DHEA and androstenedione) determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) of eight thoroughbred mares sampled longitudinally throughout pregnancy. A physiologically based model was developed to infer rates of steroid secretion during chorionic gonadotropin secretion, the luteo-placental shift and by the equine feto-placenta unit, demonstrating more variability in P5 and DHP than P4. The average of four empirical models, using nine steroids to predict GD, was calibrated (five mares, R2 = 0.94, RMSE = 20 days) and validated (three mares, R2 = 0.84, RMSE = 32 days). Validation performance was improved using paired samples taken 14 or 30 days apart (RMSE = 29 and 19 days, respectively). A second validation used an ind ependent dataset (single serum samples from 56 mixed breed mares, RMSE = 79 days) and an additional longitudinal subset from the same population sampled monthly throughout gestation (seven mares, RMSE = 42 days). Again, using paired samples improved model performance (RMSE = 32.5 days). Despite less predictive performance of the mixed breed than the thoroughbred datasets, these models demonstrate the feasibility and potential for using maternal steroid metabolomic algorithms to estimate the stage of gestation in pregnant mares and perhaps monitor fetal development. [ABSTRACT FROM AUTHOR]

Throughout pregnancy, the maternal peripheral circulation contains valuable information reflecting pregnancy progression, detectable as tightly regulated immune dynamics. Local immune processes at the maternal-fetal interface and other reproductive and non-reproductive tissues are likely to be the pacemakers for this peripheral immune "clock." This cellular immune status of pregnancy can be leveraged for the early risk assessment and prediction of spontaneous preterm birth (sPTB). Systems immunology approaches to sPTB subtypes and cross-tissue (local and peripheral) interactions, as well as integration of multiple biological data modalities promise to improve our understanding of preterm birth pathobiology and identify potential clinically actionable biomarkers., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Prenatal cadmium exposure has been associated with adverse neurodevelopmental outcomes. However, previous findings are contradictory, and little is known about the potential modifiers of the cadmium-related neurodevelopmental risk. We investigated the associations between prenatal cadmium exposure and neurodevelopment in 2-year-old children and examined the influence of mother/child characteristics. Methods: We recruited 3545 mother–child pairs from the Japan Environment and Children’s Study. We collected maternal blood during mid/late pregnancy and cord blood at delivery, and measured cadmium concentrations using inductively coupled plasma mass spectrometry. Neurodevelopment was assessed using the Kyoto Scale of Psychological Development (KSPD), which includes cognitive-adaptive (C-A), language-social (L-S), postural-motor (P-M) and developmental quotient (DQ) domains. Associations between cadmium and KSPD scores were tested using multivariable models after controlling for confounders. Results: Median levels (interquartile ranges) of cadmium in maternal and cord blood were 0.70 (0.52–0.95) and 0.04 (0.03–0.06) μg/L, respectively. Maternal blood cadmium concentrations were inversely associated with P-M scores in boys (β = −1.4, 95% confidence interval (CI): −2.7, −0.038), DQ in children of mothers who smoked during pregnancy (β = −2.9, 95% CI: −5.7, −0.12), P-M (β = −5.4, 95% CI: −10, −0.67), C-A (β = −6.1, 95% CI: −11, −1.8), L-S (β = −9.0, 95% CI: −13, −4.8) and DQ scores (β = −6.4, 95% CI: −9.6, −3.1) in children born to mothers with gestational diabetes. Cord blood cadmium concentrations were negatively associated with L-S scores (β = −6.0., 95% CI: −11, −0.91) in children born to mothers with gestational diabetes. Conclusions: Prenatal cadmium exposure was negatively associated with neurodevelopment in boys, in children whose mothers smoked, and in children born to mothers with gestational diabetes. Further studies in other populations are needed to confirm our findings.

Background: Preterm birth, defined as parturition before 37 completed weeks of gestation, is associated with an increased risk of neonatal complications and death, as well as poor health and disease later in life. Epigenetics could contribute to the mechanism underlying preterm birth. Results: Genome-wide DNA methylation analysis of whole blood cells from 10 women (5 term and 5 preterm deliveries) was performed using an Illumina Infinium HumanMethylation450 BeadChips array. We identified 1,581 differentially methylated CpG sites in promoter regions between term and preterm birth. Although the differences were not significant after correcting for multiple tests, seven CpGs on the genomically imprinted vault RNA2-1 (VTRNA2-1; also known as non-coding RNA, nc886 or miR-886) showed the largest differences (range: 26–39 %). Pyrosequencing verification was performed with blood samples from pregnant women recruited additionally (39 term and 43 preterm deliveries). In total, 28 (34.1 %) samples showed hypomethylation of the VTRNA2-1 promoter (< 13 % methylation), while 54 (65.9 %) samples showed elevated methylation levels between 30 and 60 %. Elevated methylation of VTRNA2-1 promoter was associated with an increased risk of preterm birth after adjusting for maternal age, season of delivery, parity and white blood cell count. The mRNA expression of VTRNA2-1 was 0.51-fold lower in women with preterm deliveries (n = 20) compared with women with term deliveries (n = 20). Conclusions: VTRNA2-1 is a noncoding transcript to environmentally responsive epialleles. Our results suggest that elevated methylation of the VTRNA2-1 promoter may result in increased risk of PTB caused by the pro-inflammatory cytokines. Further studies are needed to confirm the association of VTRNA2-1 methylation with preterm birth in a large population, and to elucidate the underlying mechanism. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg) is one type of mercury (Hg) species known to be very toxic to humans, especially pregnant women and their fetuses. This study aims to obtain and validate the optimum condition of liquid chromatography with inductively coupled plasma mass spectrometry (LC-ICP-MS) to test MeHg concentration. To date, there is limited research that is focused on the maternal blood MeHg samples using LC-ICPMS in Malaysia. Before analysis, collected blood (500 μL) was placed into a 15 mL polypropylene test tube, followed by the addition of extractant solution [0.10% (v/v) HCl + 0.05% (m/v) L-cysteine + 0.10% (v/v) 2-mercaptoethanol] to the sample and sonicated for 15 minutes. The MeHg level was detected from the sample solution using the LC with Zorbax Eclipse XDB-C18 (4.6 x 12.5 mm, 5 μm) (Agilent Technologies) guard column and analytical column (4.6 x 150 mm, 5 μm) and was quantified by using the ICP-MS. The recovery of MeHg was in the range of 106 to 112% with RSD of less than 10%, followed by the LOD and LOQ values of 0.216 and 0.766 μg/L, respectively. The MeHg appeared at a retention time of fewer than 5 minutes. The results reported that the median (IQR) of maternal blood MeHg level in Malaysian pregnant women was 1.70 (8.90) μg/L, which is 9.7% lower than the LOD value and 11.2% higher than the guideline value of 3.5 μg/L of MeHg in maternal blood. [ABSTRACT FROM AUTHOR]

Background: Breast milk can be a source of toxic material, along with the transfer of nutrients needed for infant growth. This study was conducted to measure the level of lead in maternal and neonatal blood and breast milk in Tehran, Iran.Methods: In this cross-sectional study, 150 mothers and their infants were studied. Samples of maternal blood, fetal umbilical cord blood, breast milk, and amount of lead measured by atomic absorption method were collected. Correlations between lead levels and demographic characteristics of mother and infants were assessed.Results: The mean levels of lead in maternal and neonatal blood and breast milk were 9.79±4.31, 8.29±4.83, and 8.65±3.67 μg/dl, respectively. The different levels of lead were associated with cord blood, maternal blood, and breast milk. No significant relationship was found between lead levels and neonatal parameters (i.e., weight, height, and head circumference). The Spearman's correlation also showed the association between different levels of lead with cord blood, maternal blood, and breast milk. Linear regression also did not show any relationship between lead levels in cord blood, milk, and mother blood with newborn growth parameters.Conclusion: The present study failed to find a significant correlation between lead and newborn birth parameters. In our study, lead levels in maternal blood, breast milk, and cord blood were lower, compared those of the previous years in Iran; however, it needs to decrease, because lead even at very low concentrations may also have adverse effects.

Abstract Background Elevated post-prandial blood glucose during pregnancy has been associated with adverse pregnancy and offspring outcomes, such as maternal gestational diabetes and excessive foetal growth. The ROLO Study is a randomized controlled trial (RCT) investigating the effect of a low glycaemic index (GI) diet in pregnancy to prevent foetal macrosomia (birth weight > 4000 g). We described the impact of a low-GI diet on the maternal and feto-placental unit metabolism by studying how the ROLO intervention affected maternal and cord blood metabolomes. Methods Fasting maternal plasma samples pre- and post-intervention of 51 pregnant women and 132 cord blood samples were measured with a targeted metabolomics approach using liquid-chromatography coupled to tandem mass spectrometry. The differences between RCT groups were explored via multivariate models with covariates correction. Significance was set at Bonferroni-corrected level of 0.05. Results A total of 262 metabolites species, sums and ratios were investigated. While no metabolite reached statistical significance after Bonferroni correction, many maternal phospholipids and acylcarnitines were elevated in the intervention group at uncorrected 0.05 alpha level. Most species contained saturated and monounsaturated fatty acid chains with 16 or 18 carbon atoms. In cord blood, no differences were identified between RCT groups. Conclusions A low-GI diet in pregnancy was associated with a trend to modest but consistent changes in maternal lipid and fatty acid metabolism. The intervention seemed not to affect foetal metabolism. Our exploratory findings may be used to direct further investigations about low GI diets before and during pregnancy, to improve patient care for pre-conceptional and pregnant women with lipid dysregulations and potentially modulate the offspring’s risk for future metabolic diseases. Trial registration Current Controlled Trials ISRCTN54392969.

Abstract Background The effects of prenatal exposure to toxic elements on birth outcomes and child development have been an area of concern. This study aimed to assess the profile of prenatal exposure to toxic elements, arsenic (As), bismuth (Bi), cadmium (Cd), mercury (total mercury (THg), methylmercury (MHg), inorganic mercury (IHg)), lead (Pb), antimony (Sb) and tin (Sn), and essential trace elements, copper (Cu), selenium (Se) and zinc (Zn), using the maternal blood, cord blood and placenta in the Tohoku Study of Child Development of Japan (N = 594–650). Methods Inductively coupled plasma mass spectrometry was used to determine the concentrations of these elements (except mercury). Levels of THg and MeHg were measured using cold vapour atomic absorption spectrophotometry and a gas chromatograph-electron capture detector, respectively. Results Median concentrations (25th–75th) of As, Cd, Pb, Sb, Sn and THg in the maternal blood were 4.06 (2.68–6.81), 1.18 (0.74–1.79), 10.8 (8.65–13.5), 0.2 (0.06–0.40) and 0.2 (0.1–0.38) ng mL−1 and 5.42 (3.89–7.59) ng g−1, respectively. Median concentrations (25th–75th) of As, Cd, Pb, Sb, Sn and THg in the cord blood were 3.68 (2.58–5.25), 0.53 (0.10–1.25), 9.89 (8.02–12.5), 0.39 (0.06–0.92) and 0.2 (0.2–0.38) ng mL−1 and 9.96 (7.05–13.8) ng g−1, respectively. Conclusions THg and Sb levels in the cord blood were twofold higher than those in the maternal blood. Cord blood to maternal blood ratios for As, Cd and Sb widely varied between individuals. To understand the effects of prenatal exposure, further research regarding the variations of placental transfer of elements is necessary.

Overweight/obesity is the main risk factor for gestational diabetes mellitus (GDM). In our cohort of pregnant women with GDM, n = 19, and without, n = 22, we previously reported a significant increase in SOCS3 mRNA expression (+62%) in visceral adipose tissue (VAT) according to GDM, without altered promoter DNA-methylation. Here, we examined methylation status of additional SOCS3 exon 2 regions in VAT and maternal blood. We found significantly altered methylation at specific CpG sites corresponding to aberrant mRNA expression levels of SOCS3 in VAT. We propose a potential regulatory element/region within exon 2; however, this region does not appear to be a good blood-marker representing VAT. [ABSTRACT FROM AUTHOR]

• Noninvasive prenatal analysis (NIPT) provides safe fetal RHD genotyping for early identification of risk pregnancies. • NIPT's beneficial application, in conjunction with quantitative maternal alloantibody analysis, is investigated in this systematic review/meta-analysis. • NIPT is highly sensitive/specific for fetal RHD genotyping beyond 11-week gestation. • Amplifications from ≥2 exons are optimum to increase NIPT accuracy. • Cut-off titer ≥8-up-to-32 is relevant for anti-D alloantibodies, while being lower for anti-K. • NIPT allows evidence-based provision of routine anti-D immunoprophylaxis. Hemolytic disease of fetus and newborn (HDFN) imposes great healthcare burden being associated with maternal alloimmunization against parental-inherited fetal red blood cell antigens causing fetal anemia or death. Noninvasive prenatal analysis (NIPT) provides safe fetal RHD genotyping for early identification of risk pregnancies and proper management guidance. We aimed to conduct systematic review and meta-analysis on NIPT's beneficial application, in conjunction with quantitative maternal alloantibody analysis, for early diagnosis of pregnancies at risk. Search for relevant articles was done in; PubMed/Medline, Scopus, and Ovid (January 2006 April 2020), including only English-written articles reporting reference tests and accuracy data. Nineteen eligible studies were critically appraised. NIPT was estimated highly sensitive/specific for fetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons are optimum to increase accuracy. NIPT permits cost-effectiveness, precious resources sparing, and low emotional stress. Knowledge of parental ethnicity is important for correct NIPT result interpretations and quantitative screening. Cut-off titer ≥8-up-to-32 is relevant for anti-D alloantibodies, while, lower titer is for anti-K. Alloimmunization is influenced by maternal RHD status, gravida status, and history of adverse obstetrics. In conclusion, NIPT allows evidence-based provision of routine anti-D immunoprophylaxis and estimates potential fetal risks for guiding further interventions. Future large-scale studies investigating NIPT's non- RHD genotyping within different ethnic groups and in presence of clinically significant alloantibodies are needed. [ABSTRACT FROM AUTHOR]

To develop an appropriate sampling strategy to assess the intrauterine exposure to dechlorane plus (DP), we investigated DP levels in sequential maternal blood samples collected in three trimesters of pregnancy, respectively, from women living in Taizhou. The median concentration of DPs (sum of syn-DP and anti-DP) in all samples was 30.5 pg g−1 wet-weight and 5.01 ng g−1 lipid-adjusted weight, respectively. The trimester-related DP concentrations were consistently strongly correlated (p < 0.01), indicating that a single measurement of DP levels could represent intrauterine exposure without sampling from the same female repeatedly; however, the wet-weight levels significantly increased across trimesters (p < 0.05), while the lipid-adjusted levels did not significantly vary. Notably, whether lipid-adjusted weight or wet-weight levels, the variation extent of DP across trimesters was found to be less than 41%, and those for other persistent organic pollutants (POPs) reported in the literature were also limited to 100%. The limitation in variation extents indicated that, regardless of the time of blood collection during pregnancy and how the levels were expressed, a single measurement could be extended to screen for exposure risk if necessary. Our study provides different strategies for sampling the maternal blood to serve the requirement for assessment of in utero exposure to DP.

Objectives: Pre‐eclampsia is a leading cause of morbidity and mortality during pregnancy. Although the two forms of this disorder, early‐ (EOPE) and late‐onset of pre‐eclampsia (LOPE) are different, the underlying pathology remains elusive. We aim to unravel the difference and to identify novel biomarkers for EOPE and LOPE. Materials and Methods: A complete comparison of both placental and peripheral blood transcriptomes was performed to investigate the pathology of pre‐eclampsia. Single‐cell transcriptomics of the maternal‐fetal interface were integrated to identify novel biomarkers for EOPE and LOPE which were further verified at protein or mRNA level in patients. Results: We found that the transcriptomes of placentae from EOPE, but not LOPE, were significantly different from their respective controls. Conversely, the transcriptomes of peripheral blood from LOPE were more different from their controls than EOPE. Importantly, we identified that several classical biomarkers of pre‐eclampsia were expressed specifically in extravillous trophoblast and syncytiotrophoblast and only upregulated in EOPE, suggesting they should not be applied to all pre‐eclampsia patients in general. We further identified novel biomarkers for EOPE and LOPE from differentially expressed genes (DEGs) of placental and peripheral blood, respectively. The new biomarkers EBI3, IGF2, ORMDL3, GATA2 and KIR2DL4 were experimentally verified with patient blood samples. Conclusion: Our data demonstrate distinct pathology of EOPE and LOPE, and uncover new biomarkers that can be applied in diagnosis for pre‐eclampsia. [ABSTRACT FROM AUTHOR]

Preterm birth (PTB) affects one in six Black babies in the United States. Epigenetics is believed to play a role in PTB; however, only a limited number of epigenetic studies of PTB have been reported, most of which have focused on cord blood DNA methylation (DNAm) and/or were conducted in white populations. Here we conducted, by far, the largest epigenome-wide DNAm analysis in 300 Black women who delivered early spontaneous preterm (sPTB, n = 150) or full-term babies (n = 150) and replicated the findings in an independent set of Black mother-newborn pairs from the Boston Birth Cohort. DNAm in maternal blood and/or cord blood was measured using the Illumina HumanMethylation450 BeadChip. We identified 45 DNAm loci in maternal blood associated with early sPTB, with a false discovery rate (FDR)

The aim of this study is to compare ADAMTS (A Disintegrin and Metalloprotease Domains with Thrombospondins motifs) 1, 4, 12, and 13 levels in maternal and cord blood and placental tissue between preeclampsia and uncomplicated pregnancies. The enzyme-linked immunosorbent assay (ELISA) results showed that ADAMTS 1, 4, 12, and 13 levels in the maternal and cord blood were lower in the preeclampsia group than in the control group. Based on the immunohistochemistry (IHC) results, ADAMTS 1, 4, and 12 levels in placental tissues were higher in the preeclampsia group. According to the polymerase chain reaction (PCR) results, ADAMTS 1, 4, and 12 were higher, whereas ADAMTS 13 was lower in the preeclampsia group than in the control group.

Objective: Lactation is associated with a dramatic increase of maternal bone turnover, leading to a reversible bone loss. Early life nutrition may influence later osteoporosis risk. Proteins synthesized by the group of wingless (Wnt) genes are key mediators of osteoblastogenesis and bone formation. We aimed to investigate maternal milk and serum concentrations of the inhibitors of the Wnt signaling pathway, Dickkopf-1 (DKK-1) and sclerostin.Material and methods: In 80 women, maternal milk and serum concentrations of DKK-1 and sclerostin were determined by ELISA on the 3rd-4th day postpartum. Concentrations were associated with various maternal, gestational and neonatal characteristics.Results: DKK-1 and sclerostin were detectable in early milk [mean ± SD: 817.17 ± 259.61 pg/mL, median (range) 258.04 (2452.40-53.17) pg/mL, respectively] at significantly lower concentrations than in maternal serum [mean ± SD: 3375.36 ± 416.75 pg/mL, median (range) 16 200.54 (58 832.00-3012.60) pg/mL, respectively], (p < .000). Maternal milk sclerostin concentrations positively correlated with respective serum ones (r = 0.599, p = .000). Maternal serum and milk sclerostin concentrations positively correlated with maternal body mass index (r = 0.37, p = .001 and r  =0.38, p = .000, respectively), while maternal serum sclerostin concentrations were higher in primiparas (p = .002).Conclusion: DKK-1 and sclerostin are present in early human milk at significantly lower concentrations, compared with maternal serum, probably contributing to the short- and long-term benefits of mother's milk for bone health. Moreover, the large amounts of both substances in maternal serum may represent disruption of the Wnt cascade, contributing to the well-known lactation-associated bone loss, which seems to be greater in primiparas and obese mothers. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the steroidome in GDM+ and GDM− women and its changes from 24 weeks (± of gestation) to labor. The study included GDM+ (n = 44) and GDM− women (n = 33), in weeks 24–28, 30–36 of gestation and at labor and mixed umbilical blood after delivery. Steroidomic data (101 steroids quantified by GC-MS/MS) support the concept that the increasing diabetogenic effects with the approaching term are associated with mounting progesterone levels. The GDM+ group showed lower levels of testosterone (due to reduced AKR1C3 activity), estradiol (due to a shift from the HSD17B1 towards HSD17B2 activity), 7-oxygenated androgens (competing with cortisone for HSD11B1 and shifting the balance from diabetogenic cortisol towards the inactive cortisone), reduced activities of SRD5As, and CYP17A1 in the hydroxylase but higher CYP17A1 activity in the lyase step. With the approaching term, the authors found rising activities of CYP3A7, AKR1C1, CYP17A1 in its hydroxylase step, but a decline in its lyase step, rising conjugation of neuroinhibitory and pregnancy-stabilizing steroids and weakening AKR1D1 activity.