Elevated levels of apolipoprotein A4 in umbilical cord serum from the maternal major depressive disorder.

AIM: Prenatal maternal depression is known to affect the neurodevelopment of offspring. This study aimed to investigate the profile of umbilical cord serum in mothers with major depressive disorder (MDD). METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS) was conducted using umbilical cord serum from mothers with MDD (n = 5) and controls (control, n = 5). The levels of several differentially expressed proteins in umbilical cord serum were compared between the MDD (n = 10) and control groups (n = 10) by enzyme-linked immunosorbent assay. RESULTS: The proteomic profiles in the umbilical cord serum were different between the MDD and control groups, including the pathways of regulation of plasma lipoprotein particle levels, and synapse organization. Only apolipoprotein A4 (APOA4) was significantly higher in the cord blood of MDD group. APOA4 levels in maternal serum were also significantly higher in the MDD group than those in the control group. The APOA4 levels in the umbilical cord serum were higher than that in the maternal serum. CONCLUSIONS: The levels of APOA4, a biomarker of depression, in the umbilical cord serum at birth were elevated in the neonates of MDD mothers. It is, therefore, likely that fetuses of MDD mothers were exposed to higher APOA4 levels in utero and this could have developmental and mental health implications for the offspring.

Comparison of prenatal and postnatal exposure to neonicotinoids and their temporal trends in breast milk.

Although the potential effects of neonicotinoids (NEOs) in early life have received considerable attention, data on the exposure of mothers and infants to NEOs are scarce. In this study, four parent NEOs and one metabolite were widely detected in paired maternal serum (MS), umbilical cord serum (UCS) and breast milk (BM) samples, with median total NEO concentrations (ΣNEOs) of 113, 160 and 69 ng/L, respectively. Decreasing trends were observed for N-desmethyl-acetamiprid (30 %/year), acetamiprid (22 %/year) and ΣNEOs (15 %/year) in breast milk between 2014 and 2022, whereas increasing trends were seen for clothianidin (17 %/year) and thiamethoxam (30 %/year). N-desmethyl-acetamiprid was the predominant compound in all matrices. However, the contributions of N-desmethyl-acetamiprid (35 %) and thiamethoxam (36 %) in breast milk were similar in 2022. Moreover, thiamethoxam has become the predominant contributor to the estimated daily intake of ΣNEOs since 2018, with the highest contribution of 71 % in 2022, suggesting the effects of NEOs continue to evolve and more attention should be paid to the new NEOs. Notably, the correlations and ratios of NEOs between paired UCS and MS were more significant and higher than those between paired BM and MS, respectively, indicating that NEO exposure was largely affected by the prenatal period.

Assessment of maternal phthalate exposure in urine across three trimesters and at delivery (umbilical cord blood and placenta) and its influence on birth anthropometric measures.

Phthalates, commonly used in plastic manufacturing, have been linked to adverse reproductive effects. Our research from the Saudi Early Autism and Environment Study (2019-2022), involving 672 participants, focused on the impacts of maternal phthalate exposure on birth anthropometric measures. We measured urinary phthalate metabolites in 390 maternal samples collected during each of the three trimesters of pregnancy and in cord serum and placental samples obtained at delivery. We employed various statistical methods to analyze our data. Intraclass correlation coefficients were used to assess the consistency of phthalate measurements, generalized estimating equations were used to explore temporal variations across the trimesters, and linear regression models, adjusted for significant confounders and Bonferroni correction, were used for each birth outcome. Exposure to six phthalates was consistently high across trimesters, with 82 %-100 % of samples containing significant levels of all metabolites, except for mono-benzyl phthalate. We found a 3.15 %-3.73 % reduction in birth weight (BWT), 1.39 %-1.69 % reduction in head circumference (HC), and 3.63 %-5.45 % reduction in placental weight (PWT) associated with a one-unit increase in certain urinary di(2-ethylhexyl) phthalate (DEHP) metabolites during the first trimester. In the second trimester, exposure to MEP, ∑7PAE, and ∑LMW correlated with a 3.15 %-4.5 % increase in the APGAR 5-min score and increases in PWT by 8.98 % for ∑7PAE and 9.09 % for ∑LMW. Our study also highlighted the maternal-to-fetal transfer of DEHP metabolites, indicating diverse impacts on birth outcomes and potential effects on developmental processes. Our study further confirmed the transfer of DEHP metabolites from mothers to fetuses, evidenced by variable rates in the placenta and cord serum, with an inverse relationship suggesting a passive transfer mechanism. Additionally, we observed distinct phthalate profiles across these matrices, adversely impacting birth outcomes. In serum, we noticed increases associated with DEHP metabolites, with birth gestational age rising by 1.01 % to 1.11 %, HC by 2.84 % to 3.67 %, and APGAR 5-min scores by 3.77 % to 3.87 %. Conversely, placental analysis revealed a different impact: BWT decreased by 3.54 % to 4.69 %, HC reductions ranged from 2.57 % to 4.69 %, and chest circumference decreased by 7.13 %. However, the cephalization index increased by 3.67 %-5.87 %. These results highlight the complex effects of phthalates on fetal development, indicating their potential influence on crucial developmental processes like sexual maturation and brain development.

Occurrence of rare earth elements in umbilical cord serum and association with thyroid hormones and birth outcomes in newborns.

Rare earth elements (REEs) are emerging contaminants that are increasingly used in high technology products. However, limited information is available regarding exposure to REEs and associated health effects in neonates. This study aimed to investigate the association between REE concentrations and thyroid hormone levels, as well as birth outcomes in 109 newborns in Beijing, China. We measured the concentrations of 16 REEs and thyroid hormones in umbilical cord serum. To assess the impact of exposure to individual REEs and REE mixtures on thyroid hormone levels and birth outcomes, we employed univariate linear regression, least absolute shrinkage and selection operator (LASSO), and weighted quantile sum (WQS) models. We detected 14 REEs at high rates (92.6%-100%), with yttrium exhibiting the highest median (interquartile range) concentration [43.94 (0.33-172.55) ng/mL], followed by scandium [3.64 (0.46-11.15) ng/mL]. Univariate analyses showed that per logarithmic (ln)-unit change of neodymium (Nd) and samarium (Sm) was associated with 0.039 [95% confidence interval (CI): 0.001, 0.007] and 0.031 (95% CI: 0.003, 0.060) increases in free thyroxine (FT4) levels, respectively. Moreover, 14 REEs exhibited significant associations with triiodothyronine (T3) levels, resulting in increases ranging from 0.066 to 0.307. Elevated concentrations of terbium (Tb) [per ln-unit change: -0.021 (95% CI: -0.041, -0.01)] and lutetium (Lu) [-0.023 (95% CI: -0.043, -0.002)] were inversely correlated with birth length in newborns. A further multiple exposure analysis employing the LASSO model identified Sm, Nd, Y, Sc, and Lu as critical factors influencing FT4 and T3 levels. Additionally, WQS analyses showed positive associations between exposure to a mixture of 14 REEs and FT4 (P = 0.046), T3 (P < 0.001), and birth length (P = 0.049). These findings suggest that in utero exposure to REEs might disrupt thyroid hormone homeostasis and impact intrauterine growth. Further studies are warranted to validate these findings and elucidate the underlying mechanisms.

Dioxins and furans maternal transfer: A study of breast milk and cord serum levels among Lebanese mothers and associations with newborn anthropometric measurements.

Dioxins and furans (PCDD/Fs) are anthropogenic pollutants that persist in the environment for long years, bioaccumulating in food & contaminating humans. In pregnancy, they can transfer through the placenta and reach the fetus, which negatively affects fetal growth. They can also reach newborns through breastfeeding. In this study, we focused on this critical subpopulation and identified the presence of PCDD/Fs among pregnant women in breast milk (n = 41) and cord serum (n = 49); we assessed the correlation between different matrices, evaluated the predictors and associations with newborn anthropometric measurements. Over 70.7 % of PCDD/Fs were detected in breast milk and 46.9-55.1 % in cord serum. Cord/maternal serum and breast milk to maternal serum ratios were > 1 with a significant positive Spearman correlation (0.669-0.729). Breast milk & maternal serum PCDD/Fs were associated inversely with age and positively with red meat intake. Cord serum PCDD/Fs were inversely associated with pre-pregnancy weight loss and passive smoking. Parity and gestational weight gain showed positive associations with Z-scores at birth. Z-score differences showed negative and positive associations with passive smoking and pre-pregnancy BMI respectively.

Metabolomics profiling of maternal and umbilical cord blood in normoglycemia macrosomia.

Background: Macrosomia is a common disorder that occurs during pregnancy. We investigated the comprehensive metabolite profiles of pregnant maternal and fetal sera in normoglycemic macrosomia in a Chinese population. Methods: Forty pregnant women and their fetuses were included in the study (twenty macrosomia patients and twenty normal-weight controls). Maternal and umbilical cord serum metabolites were identified using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Results: In total, 203 metabolites were identified. Lipids and lipid-like molecules were the predominant metabolites. Fifty-three metabolites with significant differences were obtained in the maternal samples. In the macrosomia group, the levels of docosahexaenoic acid, eicosapentaenoic acid, and arachidonic acid were significantly higher than those in the control group. Umbilical cord serum samples were obtained for 24 different metabolites. The maternal-fetal gradient of polyunsaturated fatty acids was decreased in the macrosomia group. Aconitic acid, citric acid, isocitric acid, 2-methylhexanoic acid, and 12-hydroxystearic acid were the common differential metabolites in the maternal and umbilical cord serum samples. Conclusion: There were obvious metabolic abnormalities in the sera of pregnant women and fetuses with macrosomia. Lipids and lipid-like molecules were the predominant differential metabolites but had different classifications in the maternal and umbilical cord serum. These results may provide new insights into the long-term metabolic disorders associated with macrosomia.

Nonlinear Relationship Between Maternal and Cord Blood Vitamin B12 and Folate from a Chinese Population-Based Study.

Purpose: There remains a data gap on vitamin B12 and folate level in maternal and child populations. This study aimed to assess the status of vitamin B12 and folate in maternal serum (MS) and umbilical cord serum (UCS). Materials and Methods: This was a planned secondary analysis of a case-control study. A total of 858 pregnant women during late pregnancy and their newborns in the hospitals of China were included. Maternal peripheral venous blood and neonatal umbilical cord blood were collected to determine serum vitamin B12 and folate concentration. Relationship of vitamin B12 or folate concentration between MS and UCS was assessed by a quantile regression model and the non-linear relationship between them was examined. Results: Nutritional status of serum folate was better than that of vitamin B12. Prevalence of deficiency in MS vitamin B12 and folate was 73.4% and 14.2%, respectively and these figures were about 17.8% and 0.1% in UCS. Both vitamin B12 and folate levels in UCS were significantly higher than those in MS (vitamin B12: 321.0 pg/mL vs 158.3 pg/mL, folate: 16.5 ng/mL vs 7.0 ng/mL, P <0.001). The median UCS-MS ratio of vitamin B12 and folate was 2.0 (95% CI: 1.94-2.06) and 2.4 (95% CI: 2.30-2.53), respectively. The levels of folate and vitamin B12 in UCS increased nonlinearly with their increase in MS which presented an inverted U-shaped curve. Conclusion: Deficiency in vitamin B12 and folate in the women during late pregnancy in China is prevalent. Nutritional status of the two vitamins in umbilical cord serum is correlated nonlinearly with that in maternal serum. Folic acid supplementation may be accompanied with vitamin B12 to improve status of vitamin B12 and folate during pregnancy.

Cord blood triglyceride and total cholesterol in preterm and term neonates: reference values and associated factors from the Japan Environment and Children's Study.

This study aimed to investigate the associations between cord serum total cholesterol (TC) and triglyceride (TG)levels and perinatal factors and determine the reference levels of cord blood TC and TG in Japanese neonates. This was a prospective birth cohort study using data from the Japan Environment and Children's Study, which included data on births from 2011 to 2014 in Japan. TC and TG levels were determined in cord blood samples. A total of 70,535 pairs of neonates (male: 36,001, female: 34,524) and mothers were included. The mean cord blood TC and TG levels were 72.2 mg/dL and 24.4 mg/dL, respectively. Multiple regression analyses revealed that gestational age and birth weight were significantly associated with cord blood TC (coefficient -2.35, 95% confidence interval [CI] -2.40 - -2.22 and coefficient 0.002, 95% CI 0.002-0.003, respectively) and TG (coefficient 3.09, 95% CI 3.01-3.17 and coefficient - 0.009, 95% CI - 0.009-0.008, respectively) levels. Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term. Furthermore, the mean cord blood TC and TG levels decreased over the entire range of birth weight categories.    Conclusion: Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term. Furthermore, the mean cord blood TC and TG levels decreased over the entire range of birth weight categories in Japanese newborns. Maternal complications such as maternal parity, HDP, PROM, maternal obesity and income level were associated with cord TC and TG levels. What is Known: • No studies have ascertained the reference levels of cord blood lipid levels in Japan. What is New: • Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term.

Association of Metabolites, Nutrients, and Toxins in Maternal and Cord Serum with Asthma, IgE, SPT, FeNO, and Lung Function in Offspring.

The role of metabolites, nutrients, and toxins (MNTs) in sera at the end of pregnancy and of their association with offspring respiratory and allergic disorders is underexplored. Untargeted approaches detecting a variety of compounds, known and unknown, are limited. In this cohort study, we first aimed at discovering associations of MNTs in grandmaternal (F0) serum with asthma, immunoglobulin E, skin prick tests, exhaled nitric oxide, and lung function parameters in their parental (F1) offspring. Second, for replication, we tested the identified associations of MNTs with disorders in their grandchildren (F2-offspring) based on F2 cord serum. The statistical analyses were sex-stratified. Using liquid chromatography/high-resolution mass spectrometry in F0, we detected signals for 2286 negative-ion lipids, 59 positive-ion lipids, and 6331 polar MNTs. Nine MNTs (one unknown MNT) discovered in F0-F1 and replicated in F2 showed higher risks of respiratory/allergic outcomes. Twelve MNTs (four unknowns) constituted a potential protection in F1 and F2. We recognized MNTs not yet considered candidates for respiratory/allergic outcomes: a phthalate plasticizer, an antihistamine, a bile acid metabolite, tryptophan metabolites, a hemiterpenoid glycoside, triacylglycerols, hypoxanthine, and polyphenol syringic acid. The findings suggest that MNTs are aspirants for clinical trials to prevent adverse respiratory/allergic outcomes.

Comparative steroid profiling of newborn hair and umbilical cord serum highlights the role of fetal adrenals, placenta, and pregnancy outcomes in fetal steroid metabolism.

Previous steroid hormone studies concerning pregnancy and newborns have mainly focused on glucocorticoids; wider steroid profiles have been less commonly investigated. Here, we performed a comparative analysis of 17 steroids from newborn hair and umbilical cord serum at the time of delivery. The study participants (n = 42, 50% girls) were a part of the Kuopio Birth Cohort and represent usual Finnish pregnancies. The hair and cord serum samples were analyzed with liquid chromatography high resolution mass spectrometry and triple quadrupole tandem mass spectrometry, respectively. We detected high individual variations in steroid hormone concentrations in both sample matrices. The concentrations of cortisol (F), corticosterone (B), estrone (E1), estradiol (E2), dehydroepiandrosterone (DHEA), 11ß-hydroxyandostenedione (11bOHA4), 5α-androstanedione (DHA4), and 17α-hydroxypregnenolone (17OHP5) correlated positively between cord serum and newborn hair samples. In addition, F and 11bOHA4 concentrations correlated positively with each other in both newborn hair and cord serum samples. The cortisone-to-cortisol ratio (E/F) was significantly higher in cord serum than in newborn hair samples reflecting high placental 11ßHSD2 enzyme activity. Only minor sex differences in steroid concentrations were observed; higher testosterone (T) and 11-deoxycortisol (S) with lower 11bOHA4 in male cord serum, and higher DHEA, androstenedione (A4) and 11bOHA4 in female newborn hair samples. Parity and delivery mode were the most significant pregnancy- and birth-related parameters associating with F and some other adrenocortical steroid concentrations. This study provides novel information about intrauterine steroid metabolism in late pregnancy and typical concentration ranges for several newborn hair steroids, including also 11-oxygenated androgens.

Prenatal exposure to per- and polyfluoroalkyl substances and pregnancy outcome in Austria.

Per- and polyfluoroalkyl substances (PFAS) are a large group of persistent industrial chemicals that can harm reproductive health. PFAS levels were analysed to determine the current sources of exposure and possible associations between prenatal PFAS exposure and adverse pregnancy outcome. Samples from 136 mother-newborn pairs recruited between 2017 and 2019 were analysed for the presence of 31 target PFAS in maternal serum, umbilical cord serum, and placental tissue by high-performance liquid chromatography coupled to a tandem mass spectrometer. Questionnaires and medical records were used to survey sources of exposure and pregnancy outcome, including small for gestational age (SGA), fetal growth restriction (FGR), preeclampsia (PE), preterm birth, large for gestational age (LGA) and gestational diabetes mellitus (GDM). Data were analysed for individual PFAS and sum4PFAS (sum of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) serum levels) in logistic regression analyses and categorical regression analyses. Compared to data from a previous Viennese study in 2010-12, sum4PFAS levels were generally lower. Sum4PFAS serum levels of three women (2.2%) exceeded 6.9 µg/L, a level that corresponds to the recently established tolerable weekly intake (TWI) of EFSA for nursing mothers aged 35 years; in the 2010/2012 study it was 13.6%. The large contribution of unidentified extractable organofluorine (EOF) fractions to total PFAS exposure is a concern. Study site, mean maternal corpuscular hemoglobin (MCH), use of facial lotion, and owning upholstered furniture were significantly influencing maternal exposure. While no effect of sum4PFAS on pregnancy outcome could be detected, we found highest placental PFDA levels in SGA births. PFHxS levels in umbilical cord and placenta were highest in preterm births. Further studies are needed to elucidate the relationship of prenatal PFAS exposure and pregnancy outcome, in particular to confirm whether and how placental PFDA levels may contribute to an increased risk for SGA.

Mediating effect of endocrine hormones on association between per- and polyfluoroalkyl substances exposure and birth size: Findings from sheyang mini birth cohort study.

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to affect fetus growth, but current results were inconsistent and their mechanism remained unclear. OBJECTIVES: We aimed to evaluate the associations of prenatal exposure to single and/or multiple PFAS with birth size and to elucidate whether thyroid hormones and reproductive hormones mediate these associations. METHODS: A total of 1087 mother-newborn pairs from Sheyang Mini Birth Cohort Study were included in the present cross-sectional analysis. 12 PFAS, 5 thyroid hormones and 2 reproductive hormones were measured in cord serum. Multiple linear regression models and Bayesian kernel machine regression (BKMR) models were used to examine the associations of PFAS with either birth size or endocrine hormones. One-at-a-time pairwise mediating effect analysis was applied to estimate the mediating effect of single hormone in the association between individual chemical and birth size. High-dimensional mediation approach including elastic net regularization and Bayesian shrinkage estimation were further performed to reduce exposure dimension and figure out the global mediation effects of joint endocrine hormones. RESULTS: Perfluorononanoic acid (PFNA) exposure was positively associated to weight for length z score [WLZ, per log10-unit: regression coefficient (ß) = 0.26, 95% confidence intervals (CI): 0.04, 0.47] and ponderal index (PI, ß = 0.56, 95% CI: 0.09, 1.02), and PFAS mixture results fit by BKMR model showed consistent consequences. High-dimensional mediating analyses revealed that thyroid stimulating hormone (TSH) explained 6.7% of the positive association between PFAS mixtures exposure and PI [Total effect (TE) = 1.499 (0.565, 2.405); Indirect effect (IE) = 0.105 (0.015, 0.231)]. Besides, 7.3% of the PI variance was indirectly explained by 7 endocrine hormones jointly [TE = 0.810 (0.802, 0.819); IE = 0.040 (0.038, 0.041)]. CONCLUSIONS: Prenatal PFAS mixtures exposure, especially PFNA, was positively associated to birth size. Such associations were partly mediated by cord serum TSH.

Associations of perfluoroalkyl substances with adipocytokines in umbilical cord serum: A mixtures approach.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), a kind of emerging environmental endocrine disruptors, may interfere with the secretion of adipokines and affect fetal metabolic function and intrauterine development. However, the epidemiological evidence is limited and inconsistent. We examined the associations of single and multiple PFAS exposures in utero with adipocytokine concentrations in umbilical cord serum. METHODS: This study included 1111 mother-infant pairs from Sheyang Mini Birth Cohort Study (SMBCS), and quantified 12 PFAS and two adipokine in umbilical cord serum. Generalized linear models (GLMs) and Bayesian Kernel Machine Regression (BKMR) models were applied to estimate the associations of single- and mixed- PFAS exposure with adipokines, respectively. Furthermore, sex-stratification was done in each model to assess the sexually dimorphic effects of PFAS. RESULTS: 10 PFAS were detected with median concentrations (µg/L) ranging from 0.04 to 3.97, (except 2.7% for PFOSA and 1.7% for PFDS, which were excluded). In GLMs, for each doubling increase in PFBS, PFHpA, PFHxS, PFHpS, PFUnDA and PFDoDA, leptin decreased between 14.04% for PFBS and 22.69% for PFHpS (P < 0.05). PFAS, except for PFNA, were positively associated with adiponectin, and for each doubling of PFAS, adiponectin increased between 3.27% for PFBS and 12.28% for PFHxS (P < 0.05). In addition, infant gender modified the associations of PFAS with adipokines, especially the associations of PFBS, PFOA and PFHxS with adiponectin. Similarly, significant associations of PFAS mixtures with leptin and adiponectin were observed in the BKMR models. PFDA, PFOS, PFNA and PFHpS were identified as important contributors. In the sex-stratified analysis of BKMR models, the associations between PFAS mixtures and adipokines were more pronounced in males. CONCLUSIONS: PFAS levels were significantly associated with adipokines in cord serum, suggesting that intrauterine mixture of PFAS exposure may be related to decreased fetal leptin level but increased fetal adiponectin level and the associations may be sex-specific.

Perfluoroalkyl and polyfluoroalkyl substances in cord serum of newborns and their potential factors.

The demonstrated developmental and reproductive toxicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), coupled with the increasing production and use of emerging per- and polyfluoroalkyl substances (PFASs) has resulted in progressively higher human exposure levels. This has raised concerns about PFAS exposure levels in the fetus, which is highly susceptible to the potential effects of hazardous environmental chemicals. However, in utero exposure to PFASs and health implications have not been fully characterized in China. To fill this gap, we analyzed 19 PFASs in umbilical cord serum samples (n = 66). Information about the mothers and newborns was obtained through questionnaires. Associations between maternal characteristics and neonatal birth weight and PFAS concentrations were analyzed using nonparametric tests. As results, PFOA was detected in all serum samples. The highest median concentration of PFOS in umbilical serum was 1.092 ng·mL-1, followed by perfluoropentanoic acid (median: 0.633 ng·mL-1). Trifluroacetic acid and perfluoropropanoic acid were detected in cord serum for the first time, and their median concentrations were 0.229 and 0.266 ng·mL-1, respectively. Neonatal birth weight was negatively correlated with long-chain PFOS (r = -0.319, P < 0.05), and the concentrations of perfluoroundecanoic acid and perfluorododecanoic acid were significantly different between the birth weight groups. Maternal age, maternal education, diet, and nutritional supplementation during pregnancy can all affect umbilical serum exposure to PFASs. These results demonstrate that legacy PFASs remain major contributors to the composition of human PFASs, while the concentration levels of emerging short-chain alternatives have increased significantly. Modifying the mother's diet may reduce the risk of intrauterine PFAS exposure. Special attention to exposure to highly novel PFASs and confirmation of potential determinants should be taken as a priority in the plan for risk management and actions in this area.

A comparative monitoring of maternal and cord serum polychlorinated biphenyls levels from Iranian pregnant women between industrial and urban areas.

The aim of this study was to compare maternal and fetal exposure to PCBs in pregnant women from a petrochemical and gas area (PGA) and an urban area (UA), by the analyses of serum samples from mother (MS) and cord (CS). After liquid-liquid extracting, samples were analyzed for 12 PCBs congeners by gas chromatography mass spectrometer. Adjusted multiple linear regression models showed the mean levels (µg/L) of total PCBs in the MS and CS samples from the PGA (1.70 ± 0.81 and 1.19 ± 0.43) were significantly higher than those from UA (1.64 ± 0.75 and 1.07 ± 0.38). PCB 44 was predominant in both MS and CS serum samples, and in both PGA (0.80 ± 0.70 and 0.76 ± 0.67) and UA (0.79 ± 0.39 and 0.67 ± 0.34). A negative correlation was found for PCB 52 as one-unit increase in the cord serum levels was associated with 0.024 g decrease in newborn weight. Similarly, one-unit increase in the maternal serum PCB 18 concentrations were associated with 0.09 and 0.086 cm decrease in newborn height and head circumference. The serum levels of PCB 18 and 52 in the mothers who consumed meat and milk at least 1 meal/week were higher than these who consumed meat and milk never or less than 1 meal/month. The findings in this study indicated that higher maternal exposure to PCBs, as result of living in an industrialized area, leads to higher PCBs accumulation in cord blood, which consequently passes to the developing fetus. These events may cause harmful effects on both them in-utero and afterbirth growth and development.

Treatment of Severe Dry Eye in Stevens-Johnson Syndrome with Umbilical Cord Serum Eye Drops.

Purpose: To evaluate the efficacy and safety of umbilical cord serum eye drops for dry eyes in ocular Stevens-Johnson Syndrome (SJS). Patients and Methods: A pre-post test study with umbilical cord serum (UCS) eye drop for ocular SJS patient with moderate to severe dry eyes. Study was conducted at Kirana Cipto Mangunkusumo General Hospital from June 2020 to December 2020. A total of five patients (five eyes) with a diagnosis of SJS more than 6 months, dry eye symptoms, and abnormal tear stability test results were included in the study. Each patient was asked to instill UCS drop into the affected eye six times daily. Evaluation of ocular symptoms with ocular surface disease index (OSDI) questionnaires, non-invasive tear break-up time (NIBUT), Schirmer I, and keratoepitheliopathy scores was administered before applying UCS drop and at week 2 and 4 of eye drop use. Results: From June 2020 to December 2020, five eyes of five patients were evaluated in this study. Patients were aged from 22 to 71 years old with history of SJS over periods from 1 to 35 years. Three patients underwent ocular surgeries prior to the study. After four weeks of treatment, symptoms score, Schirmer I, and keratoepitheliopathy scores improved significantly, while NIBUT scores improved insignificantly. No side effects were noted during treatment. Conclusion: Administration of UCS eye drop was effective in improving symptoms and signs of dry eye in chronic SJS patients.

Optimization and application of a method to determine 24 perfluorinated compounds in umbilical cord serum by using liquid chromatography tandem mass spectrometry.

Perfluorinated compounds (PFCs) are a group of widely used synthetic chemicals. Owing to their unique chemical properties, PFCs can accumulate in the environment and living organisms. In vitro and in vivo studies have demonstrated the adverse effects of exposure to PFCs, resulting in increased concern. Therefore, a fast, reliable analytical method is crucial for human biomonitoring and health risk assessment. This study used two isotope internal standards to identify and quantify 24 PFCs in umbilical cord serum samples, based on classical liquid-liquid extraction (LLE) with liquid chromatography tandem mass spectrometry (LC-MS/MS). According to our review of the literature, this study is the first to determine the TFHSA, S4hPDS, S4hPOS, S4hPHS, SPHeS, SPNoS, and SPPeS by using this developed method. The average spiked recoveries of 24 PFCs were acceptable, ranging from approximately 64.0% to 124%; RSDs ranged from 0.74% to 11.2%; LOD and LOQ ranged from 0.013 to 0.248 µg/L and from 0.030 to 0.747 µg/L, respectively. This method was applied to measure the PFCs in umbilical cord serum samples; 24 PFCs were detected in the investigated samples, which are comparable to those reported in the literature. TFHSA, S4hPDS, S4hPOS, S4hPHS, SPHeS, SPNoS, and SPPeS were also detected in the samples, which should be investigated in further research. The sensitivity, accuracy, and precision of the developed method are sufficient for its application in large-scale biomonitoring studies.

Examination of Trace Metals and Their Potential Transplacental Transfer in Pregnancy.

With the ever-growing concern for human health and wellbeing, the prenatal period of development requires special attention since fetuses can be exposed to various metals through the mother. Therefore, this study explored the status of selected toxic (Pb, Cd, Ni, As, Pt, Ce, Rb, Sr, U) and essential trace metals (Mn, Co, Cu, Zn, Se) in the umbilical cord (UC) sera, maternal sera, and placental tissue samples of 92 healthy women with normal pregnancies. A further aim focuses on the potential transplacental transfer of these trace metals. Based on the obtained levels of investigated elements in clinical samples, it was observed that all of the trace metals cross the placental barrier and reach the fetus. Furthermore, statistical analysis revealed significant differences in levels of toxic Ni, As, Cd, U, Sr, Rb, and essential Mn, Cu, and Zn between all three types of analyzed clinical samples. Correlation analysis highlighted As to be an element with levels that differed significantly between all tested samples. Principal component analysis (PCA) was used to enhance these findings. PCA demonstrated that Cd, Mn, Zn, Rb, Ce, U, and Sr were the most influential trace metals in distinguishing placenta from maternal and UC serum samples. As, Co, and Cu were responsible for the clustering of maternal serum samples, and PCA demonstrated that the Pt level in UC sera was responsible for the clustering of these samples. Overall, the findings of this study could contribute to a better understanding of transplacental transfer of these trace metals, and shed a light on overall levels of metal exposure in the population of healthy pregnant women and their fetuses.

Elevated concentrations of chromium in maternal serum, umbilical cord serum, and cord tissue are associated with an increased risk for orofacial clefts.

Chromium (Cr) exposure during gestation causes malformations in animal experiments. In this multicenter case-control study, we initially involved 130 orofacial clefts (OFCs) and 260 controls to assess the association between Cr concentration and risk for OFCs. Then, umbilical cord serum (49 vs. 119) and cord tissue (84 vs. 142) were used to validate the association between Cr and OFCs. We found that maternal serum Cr concentrations in OFC cases were significantly higher than those in controls. Compared with the lowest tertile of maternal serum Cr concentration, the highest tertile of Cr increased the risk for OFCs [OR = 2.14 (1.14-4.05)]. In the validation cohort of umbilical cord serum and tissue, higher concentrations of Cr were associated with increased risks for OFCs in a dose-dependent manner (all Ps for trends <0.05). Cr concentrations in maternal serum and cord serum showed a positive correlation. The Cr concentration in cord serum was inversely correlated with egg and milk consumption frequencies, and the Cr concentration in cord tissue was positively associated with indoor coal burning. In conclusion, prenatal Cr exposure is a risk factor for OFCs, and indoor coal burning during pregnancy may be one of the sources of Cr exposure.

Umbilical cord serum elementomics of 52 trace elements and early childhood neurodevelopment: Evidence from a prospective birth cohort in rural Bangladesh.

BACKGROUND: Prenatal exposures to neurotoxic metals and trace elements are associated with early childhood neurodevelopmental outcomes. However, consequences of simultaneous exposure to mixtures of elements remain unclear. OBJECTIVE: To examine individual and joint effects of prenatal trace element exposure on early childhood neurodevelopment. METHODS: Using a well-established Bangladesh prospective birth cohort (2008-2011), we measured concentrations of 52 trace elements in umbilical cord serum of 569 mother-infant pairs using inductively coupled plasma mass spectrometry. Neurodevelopment was evaluated at 20-40 months of age using Bayley Scales of Infant and Toddler Development, Third Edition. Stability elastic net (ENET) was used to screen elements individually associated with the outcome; candidate exposures were combined by weighted linear combination to form a risk score representing their mixture effect on early childhood neurodevelopment. RESULTS: Stability ENET identified 15 trace elements associated with cognitive composite score and 14 associated with motor composite score, which were linearly combined to form the element risk score (ERS). Children with higher ERScognitive had lower probability of cognitive developmental delay (ORhighest vs lowest: 0.21; 95 %CI: 0.10, 0.40; P < 0.001; Ptrend < 0.001). Children with ERSmotor in the top quintile had a significantly lower risk of motor developmental delay (OR: 0.16; 95 %CI: 0.09, 0.31; P < 0.001; Ptrend < 0.001) versus the lowest quintile. In Bayesian kernel machine regression analyses, lithium [conditional posterior inclusion probability (cPIP) = 0.68], aluminum (cPIP = 0.83) and iron (cPIP = 1.00) contributed most to the lower cognitive composite score; zinc (cPIP = 1.00), silver (cPIP = 0.81), and antimony (cPIP = 0.65) mainly contributed to the change of motor composite score. CONCLUSION: Co-exposure to lithium/aluminum/iron or zinc/silver/antimony appears to impact children's neurodevelopment. ERS score reflecting maternal exposure could indicate children's risk of neurodevelopmental delay, warranting further studies to explore the underlying mechanism.