Maternal Serum Concentrations Research Articles

One-carbon metabolite supplementation increases vitamin B12, folate, and methionine cycle metabolites in beef heifers and fetuses in an energy dependent manner at day 63 of gestation.

One-carbon metabolites (OCM) are metabolites and cofactors which include folate, vitamin B12, methionine, and choline that support methylation reactions. The objectives of this study were to investigate the effects of moderate changes in maternal body weight gain in combination with OCM supplementation during the first 63 days of gestation in beef cattle on (1) B12 and folate concentrations in maternal serum (2) folate cycle intermediates in maternal and fetal liver, allantoic fluid (ALF), and amniotic fluid (AMF) and (3) metabolites involved in one-carbon metabolism and related metabolic pathways in maternal and fetal liver. Heifers were either intake restricted (RES) and fed to lose 0.23kg/d, or fed to gain 0.60kg/d (CON). Supplemented (+OCM) heifers were given B12 and folate injections weekly and fed rumen protected methionine and choline daily, while non-supplemented (-OCM) heifers were given weekly saline injections. These two treatments were combined in a 2 × 2 factorial arrangement resulting in four treatments: CON-OCM, CON+OCM, RES-OCM, and RES+OCM. Samples of maternal serum, maternal and fetal liver, ALF, and AMF were collected at slaughter on day 63 of gestation. Restricted maternal nutrition most notably increased (P ≤ 0.05) the concentration of: vitamin B12 in maternal serum, 5,10-methylenetetrahydrofolate and 5,10-methenyltetrahydrofolate in maternal liver, and of cystathionine in fetal liver; conversely, maternal restriction decreased (P = 0.05) 5,10-methylenetetrahydrofolate concentration in fetal liver. Supplementing OCM increased (P ≤ 0.05) the concentrations of: maternal serum B12, folate and folate intermediates, ALF and AMF 5-methyltetrahydrofolate concentration, and altered (P ≤ 0.02) other maternal liver intermediates including S-adenosylmethionine, dimethylglycine, cystathionine Glutathione reduced, glutathione oxidized, taurine, serine, sarcosine, and pyridoxine. These data demonstrate that OCM supplementation was effective at increasing maternal OCM status. Furthermore, these data are similar to previously published literature where restricted maternal nutrition also affected maternal OCM status. Altering OCM status in both the dam and fetus could impact fetal developmental outcomes and production efficiencies. Lastly, these data demonstrate that fetal metabolite abundance is highly regulated, although the changes required to maintain homeostasis may program altered metabolism postnatally.

Folate deficiency in pregnancy and the risk of preterm birth: A nested case-control study.

Preterm birth (PTB) and its complications are important public health problems. Its aetiology is multifactorial and involves both modifiable and non-modifiable factors. Among the modifiable risk factors, micronutrient deficiencies, including maternal folate deficiency, are increasingly being studied in PTB. In this study, we estimated the prevalence of folate deficiency during pregnancy and examined its association with PTB among rural Bangladeshi women. We conducted a nested case-control study using data from a population-based cohort of 3000 pregnant women who were enrolled between 8 and 19 weeks of gestation following ultrasound confirmation of gestational age. Sociodemographic, epidemiologic, clinical, and pregnancy outcomes data were collected through home visits, while blood samples were collected at enrolment and 24-28 weeks of gestation during pregnancy. We included all women who delivered preterm (defined as live births <37 weeks of gestation) as cases (n = 235) and a random sample of women having a term birth as controls (n = 658). The main exposure was folate concentrations in maternal serum during 24-28 weeks of pregnancy. We categorised women into folate deficient (<3 ng/mL) and not deficient (≥3 ng/mL). We then performed multivariable logistic regression analysis to examine the association between maternal folate levels and PTB, adjusting for relevant covariates. Thirty-eight per cent of the enrolled pregnant women were folate deficient. Maternal serum folate deficiency was significantly associated with PTB (adjusted OR (aOR) = 1.73; 95% confidence interval (CI) = 1.27-2.36). The risk of PTB was also higher among women who were of short stature (aOR = 1.83; 95% CI = 1.27-2.63), primiparous (aOR = 1.60; 95% CI = 1.15-2.22), and had exposure to passive smoking (aOR = 1.54; 95% CI = 1.02-2.31). The prevalence of folate deficiency was high among pregnant women in rural Bangladesh, and folate deficiency was significantly associated with an increased risk of preterm birth.

Maternal serum unmetabolized folic acid concentration following multivitamin and mineral supplementation with or without folic acid after 12 weeks gestation: A randomized controlled trial.

Pregnant women are advised to take folic acid (FA) supplements before conception and during the first trimester of pregnancy. Many women continue FA supplementation throughout pregnancy, and concerns have been raised about associations between excessive FA intake and adverse maternal and child health outcomes. Unmetabolized folic acid (UMFA) is found in serum after high FA intakes and is proposed as a biomarker for excessive FA intake. We aimed to determine if removing FA from prenatal micronutrient supplements after 12 weeks of pregnancy reduces serum UMFA concentrations at 36 weeks gestation. In this double-blind, randomized controlled trial conducted in South Australia, 103 women with a singleton pregnancy were randomly assigned at 12-16 weeks gestation to take a micronutrient supplement containing noFA or 800 µg/day FA from enrollment until 36 weeks gestation. Ninety women (0 µg/day FA n = 46; 800 µg/day FA n = 44) completed the study. Mean, UMFA concentration was lower in the women randomized to the 0 µg/day group compared to the 800 µg/day FA group, 0.6 ± 0.7 and 1.4 ± 2.7 nmol/L, respectively. The adjusted mean difference (95% CI) in UMFA between the groups was [-0.85 (-1.62, -0.08) nmol/L, p = 0.03]. Maternal serum and red blood cell folate concentrations were lower in the 0 µg/day FA group than in the 800 µg/day group (median 23.2 vs. 49.3 and1335 vs. 1914 nmol/L, respectively; p < 0.001). Removing FA at 12-16 weeks gestation from prenatal micronutrient supplements reduced the concentration of UMFA at 36 weeks gestation.

P23 The influence of maternal inflammatory status on the risk of atopic eczema in offspring during infancy

Abstract Introduction and aims Maternal influences on infantile atopic eczema are complex, with emerging evidence for a protective role for maternal T helper (Th)1 inflammation during pregnancy. Substantial literature on characterization of a proinflammatory dietary pattern, led us to hypothesize that analyses of maternal diet and markers of inflammation might help identify mechanisms influencing the risk of infantile atopic eczema. The aim of this study was to examine the associations between energy-adjusted dietary inflammatory index (eDII) scores indicative of a proinflammatory diet pattern, maternal serum neopterin levels (a biomarker elevated in Th1 immune activation which counteracts Th2 inflammation seen in atopic eczema), and infantile risk of atopic eczema. Methods Within the UK Southampton Women’s Survey, scores for the eDII were derived from mothers’ diets (questionnaires at preconception, early and late pregnancy). Atopic eczema was ascertained at age 6 and 12 months using the UK Working Party Diagnostic Criteria (n = 262 and 270, respectively). Late pregnancy maternal serum neopterin levels were measured in a subsample (n = 497). Directed acyclic graphs were used to determine covariates to be included in linear regression analyses. Results A higher eDII score in late pregnancy was associated with a reduced risk of atopic eczema at age 6 months [odd ratios (OR) 0.89, 95% CI confidence interval (CI) 0.81–0.98; P = 0.02], with a similar trend at age 12 months (OR 0.91, 95% CI 0.83–1.00; P = 0.06). Consistent with this, and adjusting for maternal body mass index, education, smoking during pregnancy, and recent eczema, and infant filaggrin single-nucleotide polymorphism rs7512552, breastfeeding duration and sex, higher maternal serum concentrations of neopterin were associated with lower risks of infant eczema at age 6 months (OR 0.72, 95% CI 0.51–1.01; P = 0.05) and 12 months (OR 0.71, 95% CI 0.53–0.96; P = 0.03). Conclusions These findings suggest that a proinflammatory maternal diet that promotes a Th1 predominant environment protects the developing infant from Th2 inflammation and reduces the risk of atopic eczema.

Gestational PBDE concentrations, persistent externalizing, and emerging internalizing behaviors in adolescents: The HOME study

BackgroundPolybrominated diphenyl ethers (PBDEs) are ubiquitous environmental chemicals used as flame retardants in commercial and consumer products. Gestational PBDE concentrations are associated with adverse behaviors in children; however, the persistence of these associations into adolescence remains understudied. ObjectiveWe estimated the association of gestational PBDE serum concentrations with early adolescent self- and caregiver-reported behaviors at age 12 years and determined the consistency with previously observed associations in childhood with caregiver-reported behaviors in a prospective pregnancy and birth cohort. MethodsWe measured maternal serum concentrations of five individual PBDE congeners and created a summary exposure variable (∑5BDE: 28, −47, −99, −100 and −153) during pregnancy. At age 12 years, we assessed behaviors for 237 adolescents using self- and caregiver-reports with the Behavioral Assessment System for Children-3 (BASC3). We used multivariable linear regression models to estimate covariate-adjusted associations of lipid standardized, log10-transformed gestational PBDE concentrations with BASC3 scores. We obtained estimates and 95% confidence intervals through a bootstrapping approach. We evaluated potential effect measure modification (EMM) of adolescent sex by examining sex-stratified regression models and estimating the EMM p-values. ResultsGestational PBDE concentrations were positively associated with adolescent-reported BASC3 composite indices for inattention & hyperactivity (BDE-28, -47, −99, −100, ∑5BDE), internalizing problems (BDE-28, -47, −99), functional impairment (BDE-28, ∑5BDE), and emotional symptoms (BDE-28). Gestational PBDE concentrations were positively associated with caregiver-reported BASC3 composite indices for externalizing problems (BDE-28, -47, −99, −100, −153, ∑5BDE) and behavioral symptoms (BDE-99). For caregiver reported behaviors, we observed stronger associations with gestational BDE concentrations among males, especially for executive functioning (BDE-28, -47, −99, −100, ∑5BDE). DiscussionGestational PBDE serum concentrations were associated with self-reported internalizing and externalizing behavior problems in early adolescence. Caregiver-reported externalizing behaviors recognized during childhood remain associated with gestational PBDE concentrations and persist into early adolescence. Internalizing behaviors were less recognized by caregivers.

Levels of serum β-human chorionic gonadotropin after embryo transfer and subsequent miscarriage, pre-eclampsia, and intrauterine growth restriction.

This study aimed to examine maternal serum concentration of β-human chorionic gonadotropin(β-hCG) on Day 16 after embryo transfer and risk of miscarriage, pre-eclampsia, and intrauterine growth restriction (IUGR). In this study, we evaluated 125 pregnancies following in vitro fertilization (IVF). β-hCG concentrations were measured on the morning of Day 16 after embryo transfer. Baseline characteristics of the study participants were also recorded. Concentrations of β-hCG on Day 16 after embryo transfer were inversely associated with the higher risk of miscarriage (p < 0.001), but did not with pre-eclampsia and IUGR (p > 0.05). Spearman's correlation coefficient showed a reverse and significant association between β-hCG and higher risk of miscarriage (σ = 0.531andp < 0.001). There was a significant association between frozen embryo transfer and the risk of IUGR and pre-eclampsia (p = 0.005and p = 0.023, respectively). Maternal serum concentrations of β-hCG on Day 16 after IVF/embryo transfer were associated with the higher risk of miscarriage, but not pre-eclampsia and IUGR.

Impact of physical activity on preeclampsia and angiogenic markers in the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort

Introduction Effect of physical activity in pregnancy on preeclampsia (PE) and angiogenic markers is not well understood. We studied the association of physical activity and PE in a case-control setting and assessed whether exercise in PE and non-PE women associate with maternal serum concentrations of soluble fms-like tyrosine kinase 1 (s-Flt-1), placental growth factor (PlGF) and soluble endoglin (sEng) and sFlt-1/PlGF ratio in the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort. Materials and methods Participants completed a questionnaire on their background information and serum samples were collected from a subset. Questionnaire data on physical activity were available from 708 PE women and 724 non-PE women. Both first trimester serum samples and questionnaire data on physical activity were available from 160 PE women and 160 non-PE women, and second/third trimester serum samples and questionnaire data on physical activity were available from 139 PE women and 47 non-PE women. The PE and non-PE women were divided into categories of physically active (exercise 2 − 3 times/week or more) and physically inactive (exercise less than 2 − 3 times/week). Results A total of 43.4% of the PE women and 42.4% of the non-PE women were categorized as physically active. There were no differences in physical activity and exercise habits between the groups. The physically active women were more often nulliparous and non-smokers and had a lower body mass index. There were no differences in the concentrations of angiogenic markers (sFlt-1, PlGF and sEng and sFlt-1/PlGF ratio) between the groups who exercised more or less than 2 − 3 times/week. Conclusions In the FINNPEC study cohort, there was no association between physical activity and PE and no associations of physical activity in pregnant women with and without PE with maternal serum concentrations of sFlt-1, PlGF and sEng and sFlt-1/PlGF ratio.

Associations of maternal serum concentration of iron-related indicators with birth outcomes in Chinese: a pilot prospective cohort study

BackgroundPrevious studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators.MethodsA total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects’ blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records.ResultsAfter adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with − 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively.ConclusionsMaternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.

The Maternal Omega-3 Long-Chain Polyunsaturated Fatty Acid Concentration in Early Pregnancy and Infant Neurodevelopment: The ECLIPSES Study.

Omega-3 Long-Chain Polyunsaturated Fatty Acids (n-3 LCPUFAs) play a key role in early neurodevelopment, but evidence from observational and clinical studies remains inconsistent. This study investigates the association between maternal n-3 LCPUFA, Docosahexaenoic Acid (DHA), and eicosapentaenoic acid (EPA) concentrations during pregnancy and infant development functioning at 40 days. This study includes 348 mother-infant pairs. Maternal serum concentrations were assessed in the first and third trimesters alongside sociodemographic, clinical, nutritional, psychological, and obstetrical data. At 40 days, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) was administered. An adjusted analysis revealed that lower first-trimester n-3 LCPUFA and DHA concentrations are associated with better infant motor development. These results underscore the potential significance of the maternal n-3 LCPUFA status in early pregnancy for influencing fetal neurodevelopment. However, the complexity of these associations necessitates further investigation, emphasizing the urgent need for additional studies to comprehensively elucidate the nuanced interplay between the maternal n-3 LCPUFA status and infant neurodevelopment.

Exposure to Short- and Medium-Chain Chlorinated Paraffins and the Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study in Eastern China.

Toxicological studies have indicated that exposure to chlorinated paraffins (CPs) may disrupt intracellular glucose and energy metabolism. However, limited information exists regarding the impact of human CP exposure on glucose homeostasis and its potential association with an increased risk of developing gestational diabetes mellitus (GDM). Here, we conducted a prospective study with a nested case-control design to evaluate the link between short- and medium-chain CP (SCCPs and MCCPs) exposures during pregnancy and the risk of GDM. Serum samples from 102 GDM-diagnosed pregnant women and 204 healthy controls were collected in Hangzhou, Eastern China. The median (interquartile range, IQR) concentration of SCCPs was 161 (127, 236) ng/mL in the GDM group compared to 127 (96.9, 176) ng/mL in the non-GDM group (p < 0.01). For MCCPs, the GDM group had a median concentration of 144 (117, 174) ng/mL, while the control group was 114 (78.1, 162) ng/mL (p < 0.01). Compared to the lowest quartile as the reference, the adjusted odds ratios (ORs) of GDM were 7.07 (95% CI: 2.87, 17.40) and 3.34 (95% CI: 1.48, 7.53) in the highest quartile of ∑SCCP and ∑MCCP levels, respectively, with MCCPs demonstrating an inverted U-shaped association with GDM. Weighted quantile sum regression evaluated the joint effects of all CPs on GDM and glucose homeostasis. Among all CP congeners, C13H23Cl5 and C10H16Cl6 were the crucial variables driving the positive association with the GDM risk. Our results demonstrated a significant positive association between CP concentration in maternal serum and GDM risk, and exposure to SCCPs and MCCPs may disturb maternal glucose homeostasis. These findings contribute to a better understanding of the health risks of CP exposure and the role of environmental contaminants in the pathogenesis of GDM.

Maternal and Paternal Preconception Serum Concentrations of Per and Polyfluoroalkyl Substances in Relation to Birth Outcomes.

Prenatal per and polyfluoroalkyl substances (PFAS) exposure is associated with adverse birth outcomes. There is an absence of evidence on the relationship between maternal and paternal preconception PFAS exposure and birth outcomes. This study included 312 mothers and 145 fathers with a singleton live birth from a preconception cohort of subfertile couples seeking fertility treatment at a U.S. clinic. PFAS were quantified in serum samples collected before conception. Gestational age (GA) and birthweight (BW) were abstracted from delivery records. We also assessed low birthweight (BW < 2500 g) and preterm birth (GA < 37 completed weeks). We utilized multivariable linear regression, logistic regression, and quantile-based g computation to examine maternal or paternal serum concentrations of individual PFAS and mixture with birth outcomes. Maternal serum concentrations of perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS), and the total PFAS mixture were inversely associated with birthweight. Maternal PFOS concentration was associated with a higher risk of low birthweight. Conversely, paternal PFOS and PFHxS concentrations were imprecisely associated with higher birthweight. No associations were found for gestational age or preterm birth. The findings have important implications for preconception care. Future research with larger sample sizes would assist in validating these findings.

Association between prenatal exposure to indoor residual spraying insecticides and infection rates among South African children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE)

In 2021, 53 countries conducted indoor residual spraying (IRS), the application of insecticides such as dichlorodiphenyl trichloroethane (DDT) or pyrethroids to the walls of homes to control malaria. Animal studies show that these insecticides can increase susceptibility to infections but only one human study was conducted in a population from an area where IRS is applied. The aim of the present study was thus to investigate whether maternal exposure to DDT, its breakdown product dichlorodiphenyl dichloroethylene (DDE) or pyrethroid insecticides is associated with symptoms of infection among children living in a region of South Africa were IRS is conducted annually. As part of the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) we measured maternal serum concentrations of DDT and DDE, and urinary concentrations of four pyrethroid metabolites in peripartum samples. Poisson regression models with robust variance estimates were used to investigate associations with the rates of infection symptoms between ages 3.5–5 years among 629 children as assessed based on caregiver interviews. Multiple pyrethroid metabolites were associated with infection symptoms. For instance, cis-DBCA was associated with increased rates of ear infection (Incidence Rate Ratio for a 10-fold increase (IRR10) = 1.4; 95 % Confidence Interval (CI) = 1.0, 2.1) and persistent diarrhea (IRR10 = 2.1; 95 % CI = 1.2, 3.9), trans-DCCA was associated with increased rates of colds in children (IRR10 = 1.3; 95 % CI = 1.0, 1.6) and persistent fever (IRS10 = 1.4; 95 % CI = 1.0, 2.0), and 3-PBA was associated with increased rates of persistent fever (IRR10 = 1.8; 95 % CI = 1.0, 3.0). We found limited evidence of association between maternal DDE and DDT serum concentrations and infection symptoms. Results suggest that prenatal exposure to pyrethroid insecticides may be associated with infections among children from an area where IRS is conducted.

Inverse association between maternal serum concentrations of trace elements and risk of spontaneous preterm birth: a nested case-control study in China.

Few studies have evaluated the joint effect of trace elements on spontaneous preterm birth (SPTB). This study aimed to examine the relationships between the individual or mixed maternal serum concentrations of Fe, Cu, Zn, Se, Sr and Mo during pregnancy, and risk of SPTB. Inductively coupled plasma MS was employed to determine maternal serum concentrations of the six trace elements in 192 cases with SPTB and 282 controls with full-term delivery. Multivariate logistic regression, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) were used to evaluate the individual and joint effects of trace elements on SPTB. The median concentrations of Sr and Mo were significantly higher in controls than in SPTB group (P < 0·05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted OR (aOR) of 0·432 (95 CI < 0·05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted aOR of 0·432 (95 % CI 0·247, 0·756), 0·386 (95 % CI 0·213, 0·701), 0·512 (95 % CI 0·297, 0·883) and 0·559 (95 % CI 0·321, 0·972), respectively. WQSR revealed the inverse combined effect of the trace elements mixture on SPTB (aOR = 0·368, 95 % CI 0·228, 0·593). BKMR analysis confirmed the overall mixture of the trace elements was inversely associated with the risk of SPTB, and the independent effect of Sr and Mo was significant. Our findings suggest that the risk of SPTB decreased with concentrations of the six trace elements, with Sr and Mo being the major contributors.

Maternal and Neonatal Effects of Maternal Oral Exposure to Perfluoro-2-methoxyacetic Acid (PFMOAA) during Pregnancy and Early Lactation in the Sprague-Dawley Rat.

Perfluoro-2-methoxyacetic acid (PFMOAA) is a short-chain perfluoroalkyl ether carboxylic acid that has been detected at high concentrations (∼10 μg/L) in drinking water in eastern North Carolina, USA, and in human serum and breastmilk in China. Despite documented human exposure there are almost no toxicity data available to inform risk assessment of PFMOAA. Here we exposed pregnant Sprague-Dawley rats to a range of PFMOAA doses (10-450 mg/kg/d) via oral gavage from gestation day (GD) 8 to postnatal day (PND) 2 and compared results to those we previously reported for perfluorooctanoic acid (PFOA) and hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX). Newborn pups displayed reduced birthweight (≥30 mg/kg), depleted liver glycogen concentrations (all doses), hypoglycemia (≥125 mg/kg), and numerous significantly altered genes in the liver associated with fatty acid and glucose metabolism similar to gene changes produced by HFPO-DA. Pup survival was significantly reduced at ≥125 mg/kg, and at necropsy on PND2 both maternal and neonatal animals displayed increased liver weights, increased serum aspartate aminotransferase (AST), and reduced serum thyroid hormones at all doses (≥10 mg/kg). Pups also displayed highly elevated serum cholesterol at all doses. PFMOAA concentrations in serum and liver increased with maternal oral dose in both maternal and F1 animals and were similar to those we reported for PFOA but considerably higher than HFPO-DA. We calculated 10% effect levels (ED10 or EC10) and relative potency factors (RPF; PFOA = index chemical) among the three compounds based on maternal oral dose and maternal serum concentration (μM). Reduced pup liver glycogen, increased liver weights and reduced thyroid hormone levels (maternal and pup) were the most sensitive end points modeled. PFMOAA was ∼3-7-fold less potent than PFOA for most end points based on maternal serum RPFs, but slightly more potent for increased maternal and pup liver weights. PFMOAA is a maternal and developmental toxicant in the rat producing a constellation of adverse effects similar to PFOA and HFPO-DA.

Using in vitro data to derive acceptable exposure levels: A case study on PBDE developmental neurotoxicity

BackgroundCurrent acceptable chemical exposure levels (e.g., tolerable daily intake) are mainly based on animal experiments, which are costly, time-consuming, considered non-ethical by many, and may poorly predict adverse outcomes in humans. ObjectiveTo evaluate a method using human in vitro data and biological modeling to calculate an acceptable exposure level through a case study on 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) developmental neurotoxicity (DNT). MethodsWe reviewed the literature on in vitro assays studying BDE-47-induced DNT. Using the most sensitive endpoint, we derived a point of departure using a mass-balance in vitro disposition model and benchmark dose modeling for a 5% response (BMC05) in cells. We subsequently used a pharmacokinetic model of gestation and lactation to estimate administered equivalent doses leading to four different metrics of child brain concentration (i.e., average prenatal, average postnatal, average overall, and maximum concentration) equal to the point of departure. The administered equivalent doses were translated into tolerable daily intakes using uncertainty factors. Finally, we calculated biomonitoring equivalents for maternal serum and compared them to published epidemiological studies of DNT. ResultsWe calculated a BMC05 of 164 μg/kg of cells for BDE-47 induced alteration of differentiation in neural progenitor cells. We estimated administered equivalent doses of 0.925–3.767 μg/kg/day in mothers, and tolerable daily intakes of 0.009–0.038 μg/kg/day (composite uncertainty factor: 100). The lowest derived biomonitoring equivalent was 19.75 ng/g lipids, which was consistent with reported median (0.9–23 ng/g lipids) and geometric mean (7.02–26.9 ng/g lipids) maternal serum concentrations from epidemiological studies. ConclusionThis case study supports using in vitro data and biological modeling as a viable alternative to animal testing to derive acceptable exposure levels.

Maternal serum fatty acid binding protein-4 level is upregulated in fetal growth restriction with abnormal Doppler flow patterns.

This study aimed to determine fatty acid binding protein-4 (FABP-4) concentrations in maternal serum of fetal growth restriction (FGR) pregnancies and controls of normal pregnancies. Furthermore, we hypothesized that the alterations in FABP-4 levels might correlate with FGR severity. We performed this prospective case-control study with 83 pregnant women. The study groups included 26 FGR pregnancies without abnormal fetal Doppler flow patterns and 25 pregnancies complicated with FGR accompanied by abnormal fetal Doppler flow patterns. The median serum FABP-4 concentrations were significantly higher in the FGR cases with abnormal Doppler flow pattern group (2.09 ng/mL) than in the FGR cases without abnormal Doppler flow pattern group (1.62 ng/mL) and the control group (1.20 ng/mL, p < 0.001). A significant negative correlation was observed between maternal serum FABP-4 levels and time to birth from blood sample collection (r = -0.356 and p = 0.001), gestational week at birth (r = -0.386 and p < 0.001), and birth weight (r = -0.394 and p < 0.001). A 1.35 ng/mL cut-off value of serum FABP-4 level could be used to discriminate FGR cases with a 78.4% sensitivity and 60.6% specificity. The optimal cut-off value of FABP-4 levels as an indicator for the diagnosis of FGR with abnormal Doppler flow pattern was estimated to be 1.76 ng/mL, which yielded a sensitivity of 84.0% and a specificity of 75.8%. FABP-4 is a crucial biomarker in the diagnosis and determining the severity of pregnancies with restricted fetal growth. We consider that FABP-4 is a powerful, reliable, and unique biomarker to diagnose FGR pregnancies.

The Association Of Adiponectin, Homocysteine, B 12 And Folic Acid In Iraqi Women With Preeclampsia And Its Severity

Background: preeclampsia is a common obstetric disorder that remains a leading cause of maternal and perinatal mortality and morbidity. Maternal serum concentrations of adiponectin, folate, homocysteine, and vitamin B12 have been found to be associated with pre-eclampsia. Nevertheless, reported studies involved still not clear with variable reliably. The aim of the present study is to examine the relationship between these biomarkers and pre-eclampsia and its severity in Iraqi population. Aims: The study aims to evaluate the association between maternal serum adiponectin, homocysteine, B12 and Folic acid and preeclampsia and its severity. Study design and setting: A case control study carried out in Al-Zahraa Maternity and Pediatric Teaching Hospital in Najaf city/ Iraq from the 1st of December 2019 to the 1st of December 2020. Patient and Methods: The study included 50 pregnant women with preeclampsia and a comparative control group of 50 normotensive pregnant women. Preeclamptic women were further subdivided into 14 women with severe preeclampsia and 36 women with mild preeclampsia. Serum Adiponectin, Homocysteine, B 12, and Folic acid were measured by using special ELIZA (Enzyme linked immunosorbent assay) technique. Results: There was a significant increment in the level of Adiponectin and Homocysteine while vitamin B12 and Folic acid were significantly decreased in preeclamptic pregnant women in comparison to the control group. On the other hand, there was no significant relation between the severity of preeclampsia and the level of Adiponectin, Homocysteine, Vitamin B 12, and Folic acid. Conclusion: Women with preeclampsia had significantly lower vitamin B12 and folic acid and significantly higher concentrations of adiponectin and homocysteine than normotensive pregnant women, but no relation with its severity.

Maternal serum concentrations of per- and polyfluoroalkyl substances and childhood acute lymphoblastic leukemia.

Per- and polyfluoroalkyl substances (PFAS) are widespread and environmentally persistent chemicals with immunotoxic properties. Children are prenatally exposed through maternal transfer of PFAS to cord blood, but no studies have investigated the relationship with childhood leukemia. We measured maternal serum levels of 19 PFAS in first-trimester samples collected in 1986-2010 and evaluated associations with acute lymphoblastic leukemia in full-term offspring (aged younger than 15 years) for 400 cases and 400 controls in the Finnish Maternity Cohort, matched on sample year, mother's age, gestational age, birth order, and child's sex. We analyzed continuous and categorical exposures, estimating odds ratios (ORs) and 95% confidence intervals (CIs) via conditional logistic regression adjusted for maternal smoking and correlated PFAS (ρ ≥ ±0.3). We also stratified by calendar period, mean diagnosis age, and the child's sex. N-methyl-perfluorooctane sulfonamidoacetic acid was associated with acute lymphoblastic leukemia in continuous models (per each doubling in levels: ORperlog2 = 1.22, 95% CI = 1.07 to 1.39), with a positive exposure-response across categories (OR>90th percentile = 2.52, 95% CI = 1.33 to 4.78; Ptrend = .01). Although we found no relationship with perfluorooctane sulfonic acid overall, an association was observed in samples collected in 1986-1995, when levels were highest (median = 17.9 µg/L; ORperlog2 = 4.01, 95% CI = 1.62 to 9.93). A positive association with perfluorononanoic acid was suggested among first births (Pinteraction = .06). The N-methyl-perfluorooctane sulfonamidoacetic acid association was mainly limited to children diagnosed before age 5 years (Pinteraction = .02). We found no consistent patterns of association with other PFAS or differences by sex. These novel data offer evidence of a relationship between some PFAS and risk of the most common childhood cancer worldwide, including associations with the highest levels of perfluorooctanesulfonic acid and with a precursor, N-methyl-perfluorooctane sulfonamidoacetic acid.

399 Methionine and Guanidinoacetic Acid Supplementation Throughout the Periconceptual Period of Gestation Alters Metabolite Concentrations and Fetal Development

Abstract Recent research reported changes in fetal growth due to increased methyl donor availability through periconceptual supplementation of the dam. We hypothesized that maternal supplementation of methionine (MET) or guanidinoacetic acid (GAA) during the periconceptual period will result in a methyl donor surplus or deficiency in maternal serum and ultimately influence fetal body and organ weight at d +63 gestation. The objectives of this study were to evaluate effects of methyl donor surplus or deficiency during the periconceptual period of gestation on metabolite concentrations in the heifer and the effects on early fetal development. Eighty MARC II heifers (n = 20 per treatment, initial BW = 346 ± 8 kg) were stratified by age and weight to one of four treatment groups to receive 100 g of supplement: ground corn carrier as control (CON), MET (10 g/d) in ground corn, GAA (40 g/d) in ground corn, and MET + GAA (10 g/d MET + 40 g/d GAA) in ground corn. Supplementation began 63 d before breeding (d –63) until d 63 of gestation (d +63), and serum samples were collected before feeding on d -63, at breeding, and d +63. Heifers were bred using male sexed semen from the same sire, and 35 heifers were confirmed pregnant (CON, n = 10; MET, n = 8; GAA, n = 7; MET + GAA, n =10) and harvested at d +63 of gestation to collect maternal and fetal samples. Data were analyzed as a 2 × 2 factorial design with 2 levels of MET and 2 levels of GAA. Methionine concentrations in maternal serum were greater (P = 0.05) in MET and MET + GAA supplemented heifers at d 0 and d +63 compared with CON and GAA at d -63, d 0, and d +63. There were no differences (P ≥ 0.15) in the concentration of GAA or creatine due to supplementation; however, both were decreased at breeding (P &amp;lt; 0.01) compared with d -63 and d +63. Fetuses from MET supplemented heifers had greater (P = 0.01) brain weight and Longissimus muscle than dams not receiving MET. We conclude that MET supplementation during the periconceptual period can alter methyl donor availability and increase fetal muscle development. USDA is an equal opportunity provider and employer.

Predictors of Developmental Defects of Enamel in Primary Maxillary Central Incisors Using Bayesian Model Selection

Introduction: Localized non-inheritable developmental defects of tooth enamel (DDE) are classified as enamel hypoplasia (EH), opacity (OP), and post-eruptive breakdown (PEB) using the enamel defects index. To better understand the etiology of DDE, we assessed the linkages amongst exposome variables for these defects during the specific time duration for enamel mineralization of the human primary maxillary central incisor enamel crowns. In general, these two teeth develop between 13 and 14 weeks in utero and 3–4 weeks’ postpartum of a full-term delivery, followed by tooth eruption at about 1 year of age. Methods: We utilized existing datasets for mother-child dyads that encompassed 12 weeks’ gestation through birth and early infancy, and child DDE outcomes from digital images of the erupted primary maxillary central incisor teeth. We applied a Bayesian modeling paradigm to assess the important predictors of EH, OP, and PEB. Results: The results of Gibbs variable selection showed a key set of predictors: mother’s prepregnancy body mass index (BMI); maternal serum concentrations of calcium and phosphorus at gestational week 28; child’s gestational age; and both mother’s and child’s functional vitamin D deficiency (FVDD). In this sample of healthy mothers and children, significant predictors for OP included the child having a gestational period >36 weeks and FVDD at birth, and for PEB included a mother’s prepregnancy BMI <21.5 and higher serum phosphorus concentration at week 28. Conclusion: In conclusion, our methodology and results provide a roadmap for assessing timely biomarker measures of exposures during specific tooth development to better understand the etiology of DDE for future prevention.