Transplacental Transfer Efficiencies Research Articles

Transplacental transfer of RSV antibody in Australian First Nations infants.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection hospitalisations in Aboriginal infants specifically those aged <6 months. Maternally derived RSV antibody (Ab) can protect against severe RSV disease in infancy. However, the efficiency of transplacental transfer of maternal anti-RSV Ab remains unknown in Aboriginal infants. We characterised RSV Ab in Australian First Nations mother-infant pairs (n = 78). We investigated impact of covariates including low birthweight, gestational age (GA), sex of the baby, maternal age and multiparity of the mother on cord to maternal anti-RSV Ab titre ratio (CMTR) using multivariable logistic regression model. All (n = 78) but one infant was born full term (median GA: 39 weeks, interquartile range: 38–40 weeks) and 56% were males. The mean log2 RSV Ab titre was 10.7 (SD ± 1.3) in maternal serum and 11.0 (SD ± 1.3) in cord serum at birth; a ratio of 1.02 (SD ±0.06). One-third of the pairs had a CMTR of <1 indicating impaired transfer. Almost 9% (7/78) of the term infants had cord RSV Ab levels below <log2 9. Covariates showed no effect on CMTR. Further mechanistic research is needed to determine the significance of these findings on RSV disease in First Nations children.

Congenital Human Cytomegalovirus Infection Is Associated With Decreased Transplacental IgG Transfer Efficiency Due to Maternal Hypergammaglobulinemia.

Placentally transferred maternal immunoglobulin G (IgG) protects against pathogens in early life, yet vertically transmitted infections can interfere with transplacental IgG transfer. Although human cytomegalovirus (HCMV) is the most common placentally-transmitted viral infection worldwide, the impact of congenital HCMV (cCMV) infection on transplacental IgG transfer has been underexplored. We evaluated total and antigen-specific maternal and cord blood IgG levels and transplacental IgG transfer efficiency in a US-based cohort of 93 mother-infant pairs including 27 cCMV-infected and 66 cCMV-uninfected pairs, of which 29 infants were born to HCMV-seropositive nontransmitting mothers and 37 to HCMV-seronegative mothers. Controls were matched on sex, race/ethnicity, maternal age, and delivery year. Transplacental IgG transfer efficiency was decreased by 23% (95% confidence interval [CI] 10-36%, P = .0079) in cCMV-infected pairs and 75% of this effect (95% CI 28-174%, P = .0085) was mediated by elevated maternal IgG levels (ie, hypergammaglobulinemia) in HCMV-transmitting women. Despite reduced transfer efficiency, IgG levels were similar in cord blood from infants with and without cCMV infection. Our results indicate that cCMV infection moderately reduces transplacental IgG transfer efficiency due to maternal hypergammaglobulinemia; however, infants with and without cCMV infection had similar antigen-specific IgG levels, suggesting comparable protection from maternal IgG acquired via transplacental transfer.

Maternal Antibody Response, Neutralizing Potency, and Placental Antibody Transfer After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

To characterize maternal immune response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and quantify the efficiency of transplacental antibody transfer. We conducted a prospective cohort study of pregnant patients who tested positive for SARS CoV-2 infection at any point in pregnancy and collected paired maternal and cord blood samples at the time of delivery. An enzyme-linked immunosorbent assay (ELISA) and neutralization assays were performed to measure maternal plasma and cord blood concentrations and neutralizing potency of immunoglobulin (Ig)G, IgA, and IgM antibodies directed against the SARS-CoV-2 spike protein. Differences in concentrations according to symptomatic compared with asymptomatic infection and time from positive polymerase chain reaction (PCR) test result to delivery were analyzed using nonparametric tests of significance. The ratio of cord to maternal anti-receptor-binding domain IgG titers was analyzed to assess transplacental transfer efficiency. Thirty-two paired samples were analyzed. Detectable anti-receptor-binding domain IgG was detected in 100% (n=32) of maternal and 91% (n=29) of cord blood samples. Functional neutralizing antibody was present in 94% (n=30) of the maternal and 25% (n=8) of cord blood samples. Symptomatic infection was associated with a significant difference in median (interquartile range) maternal anti-receptor-binding domain IgG titers compared with asymptomatic infection (log 3.2 [3.5-2.4] vs log 2.7 [2.9-1.4], P=.03). Median (interquartile range) maternal anti-receptor-binding domain IgG titers were not significantly higher in patients who delivered more than 14 days after a positive PCR test result compared with those who delivered within 14 days (log 3.3 [3.5-2.4] vs log 2.67 [2.8-1.6], P=.05). Median (range) cord/maternal antibody ratio was 0.81 (0.67-0.88). These results demonstrate robust maternal neutralizing and anti-receptor-binding domain IgG response after SARS-CoV-2 infection, yet a lower-than-expected efficiency of transplacental antibody transfer and a significant reduction in neutralization between maternal blood and cord blood. Maternal infection does confer some degree of neonatal antibody protection, but the robustness and durability of protection require further study.

A Critical Review on Transplacental Transfer of Per- and Polyfluoroalkyl Substances: Prenatal Exposure Levels, Characteristics, and Mechanisms.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) has aroused public concerns as it can pose multiple health threats to pregnant women and cause adverse birth outcomes for fetuses. In previous studies, the prenatal exposure levels and transplacental transfer efficiencies (TTE) of PFASs have been reported and discussed. Specifically, the binding affinities between PFASs and some transporters were determined, demonstrating that the TTE values of PFASs are highly dependent on their binding behaviors. To summarize primary findings of previous studies and propose potential guidance for future research, this article provides a systematic overview on levels and characteristics of prenatal exposure to PFASs worldwide, summarizes relationships between TTE values and structures of PFASs, and discusses possible transplacental transfer mechanisms, especially for the combination between PFASs and transporters. Given the critical roles of transporters in the transplacental transfer of PFASs, we conducted molecular docking to further clarify the binding behaviors between PFASs and the selected transporters. We proposed that the machine learning can be a superior method to predict and reveal behaviors and mechanisms of the transplacental transfer of PFASs. In total, this is the first review providing a comprehensive overview on the prenatal exposure levels and transplacental transfer mechanisms of PFASs.

Transplacental Behaviors of Organophosphate Tri- and Diesters Based on Paired Human Maternal and Cord Whole Blood: Efficiencies and Impact Factors.

Organophosphate tri- and diesters (tri-OPEs and di-OPEs) were quantified in 63 paired maternal and cord whole blood samples collected in Hubei, China, in which tri-o-cresyl phosphate (ToCP) was predominant. The transplacental transfer efficiencies (expressed as cord blood to maternal blood (C:M) concentration ratios) of aryl-tri-OPEs, such as ToCP (1.61) and triphenyl phosphate (TPHP) (1.06), were higher than those of alkyl-tri-OPEs (0.66-0.76). For the target tri-OPEs and some traditional organic compounds, the C:M ratios first increased with log Kow in the range of 1.63-5.23 and then decreased, showing a parabolic relationship. However, ToCP, with a log Kow of 6.34, deviated from this relationship and displayed the highest C:M ratio (1.61). Molecular docking indicated a very strong binding affinity between ToCP and transthyretin, suggesting that ToCP might be actively transported by transthyretin in the placenta. The di-OPE levels in the blood samples were significantly lower than the corresponding tri-OPE levels, and those in the cord blood were influenced not only by their transplacental behaviors but also by their low excretion rates and the metabolic characteristics of their parent compounds in the fetus. This study provides useful information for accurately assessing the health risks posed by tri-OPEs to pregnant women and fetuses.

Transplacental Transfer of Environmental Chemicals: Roles of Molecular Descriptors and Placental Transporters.

Transplacental transfer of environmental chemicals results in direct risks to fetal development. Although numerous studies have investigated transplacental transfer efficiencies (TTEs) of environmental chemicals, the underlying mechanisms and influencing factors remain poorly understood. The present study aims to synthesize a current state of knowledge on the TTEs of major environmental chemicals and explore the roles of chemicals' molecular descriptors and placental transporters in the transplacental transfer. The results indicate great variations in TTEs (median: 0.29-2.86) across 51 chemicals. Chemical-dependent TTEs may partially be attributed to the influences of chemicals' molecular descriptors. Predictive models based on experimental TTEs and 1790 computed molecular descriptors indicate that a very limited number of molecular descriptors, such as the topological polar surface area, may substantially influence and efficiently predict chemicals' TTEs. In addition, molecular docking analyses were conducted to determine the binding affinities between 51 chemicals and six selected transporters, including BCRP, MDR1, hENT1, FRα, SERT, and MRP1. The results reveal transporter- and chemical-dependent binding affinities. Therefore, our study demonstrates that molecular descriptors and placental transporters, among a variety of other factors, can play important roles in the transplacental transfer of environmental chemicals. However, the underlying mechanisms and several important knowledge gaps identified herein require further investigations.

Prenatal exposure and transplacental transfer of perfluoroalkyl substance isomers in participants from the upper and lower reaches of the Yangtze River.

Data on gestational exposure characteristics and transplacental transfer are quite limited for perfluoroalkyl substance (PFAS) isomers, especially those from large-scale comparative studies. To fill this gap, we examined isomers of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS) in matched maternal and cord serum from Mianyang and Hangzhou, which are located in the upper and lower reaches of the Yangtze River, China, respectively. These data were compared with those from our previous study on Wuhan in the middle reach. The average ΣPFAS concentration increased from upstream to downstream (Mianyang (4.44ng/mL)<Wuhan (9.88ng/mL)<Hangzhou (19.72ng/mL)) and may be related to the per capita consumption expenditure of each city. The ln-transformed PFAS concentrations showed significant differences between Mianyang and Hangzhou after adjusting confounding factors (p<0.05). The percentages of linear PFOS and PFOA in maternal and cord serum from these cities all exceeded those in electrochemical fluorination products. The isomer profiles of PFASs in maternal and cord serum might be greatly influenced by local production processes of PFASs and residents' dietary habits. The transplacental transfer efficiencies decreased significantly with increasing concentrations in maternal serum for ΣPFAS, ΣPFOS, ΣPFOA, ΣPFHxS, n-PFOS, iso-PFOS, 4m-PFOS, 1m-PFOS, n-PFOA, n-PFHxS, and br-PFHxS (Spearman rank correlation coefficients (r)=0.373-0.687, p<0.01). These findings support an understanding of the regional characteristics in maternal exposure to PFASs along the Yangtze River, isomeric profiles of PFASs in these regions, and the transplacental transfer processes of PFAS isomers.

Immunogenicity of influenza vaccines administered to pregnant women in randomized clinical trials in Mali and South Africa

BackgroundA key consideration for expanding recommendations for influenza vaccination is a robust assessment of immunogenicity and efficiency of transplacental antibody transfer after maternal vaccination. MethodsWe pooled data from two trials of maternal influenza vaccination to analyze vaccine immunogenicity with more power than either trial had alone. We compared hemagglutination-inhibition (HAI) titers and titer factor change for women and their infants between trial arms using t-tests; maternal and infant putative seroprotective titers (HAI ≥ 1:40) within each trial arm and maternal seroconversion between trial arms using exact tests; and transplacental antibody transfer between trial arms using t-tests. We used marginal linear models and generalized estimating equations to examine the impact of time between maternal vaccination and delivery on transplacental antibody transfer, infant titers, and infant seroprotection. ResultsFor all vaccine components (A/H1N1, A/H3N2, and Type B), >80% of vaccinated women had seroprotective titers, >60% of them seroconverted, and >50% of their infants were born with seroprotective titers. These immunogenicity outcomes occurred more often in vaccine recipients and their infants than in controls. No difference in efficiency of transplacental antibody transfer was observed between vaccine recipients and controls. ConclusionsOur results provide robust support for further expansion of maternal influenza vaccination recommendations.Clinical Trials Registration: NCT01430689 and NCT01306669.

Blood partitioning and whole-blood-based maternal transfer assessment of chlorinated paraffins in mother-infant pairs from South China

As a new group of persistent organic pollutants of concern, chlorinated paraffins (CPs) have been widely detected in the environment and biota, but their occurrence, partitioning, and transfer in humans have been not well documented. In this study, 32 pairs of maternal blood, cord blood, and placenta samples were collected from pregnant women in South China, and the blood was further separated into plasma and red blood cells (RBCs) for blood partitioning study. Short- and medium-chain CPs (SCCPs and MCCPs, respectively) were detected in all the five human biological matrices, suggesting prevalent exposure and maternal transfer of CPs in the pregnant women. Discrepant congener group profiles of CPs were observed in different human biological matrices. Significant differences in the plasma-RBC partitioning of CPs in the maternal and cord bloods were identified (p < 0.001). CP partitioning to plasma was stronger than that to RBCs in maternal blood, but the converse was true for cord blood. Mass fractions in plasma (Fp) for SCCPs (mean, 0.78) and MCCPs (0.74) in maternal blood were significantly higher than the values in cord blood. Transplacental transfer efficiencies (TTEs) were evaluated based on the whole blood concentrations of CPs in the maternal and cord bloods, and the TTEs ranged from 0.50 to 0.69 (first to third quartiles) for SCCPs and MCCPs, indicating that the placenta can partially restrict maternal transfer. The extent of CP retention in the placenta was assessed by the concentration ratio (RPM) of matched placenta and maternal blood, and interestingly, a U-shaped trend for placental retention (RPM) with increasing chain length was observed for individual congener groups. Significant relationships of the CP concentrations among the maternal blood, cord blood, and placenta were observed (p < 0.001). To our knowledge, this is the first study to report the plasma-RBC partitioning of CPs in human maternal and cord bloods, as well as the first study to evaluate TTEs based on whole blood concentrations. Our study confirmed that whole blood is the preferred matrix for accurately assessing human internal exposure and transplacental transfer of CPs.

Efficiency of placental transfer of vaccine-elicited antibodies relative to prenatal Tdap vaccination status

Administration of vaccines during pregnancy provides maternal protection against infectious diseases. This protection is extended to their infants during the first months of life, as pathogen-specific antibodies formed in response to maternal vaccination are transferred across the placenta to the fetus. Notably, Tdap (tetanus-diphtheria-acellular pertussis) vaccination booster is routinely administered to pregnant women both to prevent neonatal tetanus and to ensure that infants have protective levels of pertussis antibodies until they are able to establish their own vaccine-induced levels. Whether infant protection through maternal immunization is merely due to an increase in maternal antibody levels or whether maternal immunization enhances the transfer of vaccine-specific antibodies is unclear. Moreover, the potential impact of prenatal vaccinations on the transplacental transfer of other antibodies, such as antibodies raised as a result of infections or other vaccines administered prior to pregnancy, has not been studied.The goal of this study was to define the impact of maternal vaccination on IgG transplacental transfer efficiency. We analyzed antigen-specific antibody populations and IgG subclass distribution in maternal and cord blood samples from 58 mother-infant pairs. All women received the seasonal inactivated influenza vaccine during pregnancy and 25 women received the Tdap vaccine during the second or third trimester of gestation. Prenatal Tdap vaccination did not impact the efficiency of IgG transplacental transfer; however, it was associated with higher maternal and infant vaccine-elicited Tdap-specific antibody levels, and with a higher proportion of infants with protective levels of antibodies, especially against diphtheria. There was also no difference in the IgG transplacental transfer rate of antibodies against non-Tdap vaccines between the two groups of women. Our results confirm previous reports demonstrating the benefits of prenatal Tdap immunization and indicate that this strategy does not impede the transplacental transfer of other antibodies that are also important for infant protection.

Transplacental Transfer of Per- and Polyfluoroalkyl Substances (PFASs): Differences between Preterm and Full-Term Deliveries and Associations with Placental Transporter mRNA Expression.

Previous studies demonstrated that per- and polyfluoroalkyl substances (PFASs) can cross the human placental barrier. However, their transplacental transfer efficiencies (TTEs) have not been investigated in preterm delivery, and the role of placental transport proteins has rarely been explored. Our study hypothesized that the TTEs of PFASs could differ between preterm and full-term deliveries, and some placental transporters could be involved in active maternofetal PFAS transfer. In the present study, the median TTEs of 16 individual PFAS chemicals or isomers were determined to be 0.23 to 1.72 in matched maternal-cord serum pairs with preterm delivery (N = 86), which were significantly lower than those (0.35 to 2.26) determined in full-term delivery (N = 187). Significant associations were determined between the TTEs of several PFASs and the mRNA expression levels of selected transporters located on the brush border membrane. The association patterns also significantly differed between preterm and full-term deliveries and exhibited a chemical-specific manner. For example, the expression of MRP2 exhibited significantly positive associations with the TTEs of linear and branched perfluorooctanesulfonic acid (PFOS) isomers in full-term delivery, but negative, nonsignificant associations were observed in preterm delivery. This is the first study to compare the transplacental transfer of PFASs between preterm and full-term deliveries and indicate that some placental transport proteins could be involved in active transmission. The mechanisms underlying the cross-placental transfer of PFASs require further investigations to better elucidate their risks to fetal health and birth outcomes.

Study on maternal-fetal status of Pb, Cd, As, Hg, Mn and Se elements and transplacental transfer efficiency

Objective: To understand the levels of Pb, Cd, As, Hg, Mn, and Se in maternal and umbilical cord blood, and to explore the transplacental transfer efficiency (TTE). Methods: From September 2010 to December 2013, a total of 773 pregnant women and their newborns (Laizhou Bay Birth Cohort) were recruited from a second grade hospital in the south bank of Laizhou Bay, Bohai, Shandong Province. According to different detection methods, the six measured elements are classified into three groups including the Hg measurement group (595 mother-newborn pairs), the Pb measurement group (534 mother-newborn pairs), and the Cd, As, Mn and Se measurement group (244 mother-newborn pairs). The demographic characteristics of pregnant women and their newborns were obtained by the questionnaire. The concentrations of elements in maternal and umbilical cord blood were detected and the TTE of each element (elemental concentration in cord blood/elemental concentration in maternal blood) was calculated. The correlation of elements between maternal and cord blood was analyzed using Spearman's rank correlation coefficient. Results: The mean±SD of maternal age, gestational week and newborn birth weight of 773 mother-infant pairs were (28.34±4.50) years, (39.47±1.39) weeks and (3 419.47±497.39) g respectively. The median concentrations of Pb, Cd, As, Hg, Mn and As in maternal and cord blood were 31.12 and 30.02, 1.19 and 0.47, 8.05 and 6.03, 0.69 and 1.26, 100.70 and 105.55, 127.25 and 115.00 μg/L, respectively. The TTE of Pb, Cd, As, Hg, Mn, and Se was 0.98, 0.41, 0.73, 1.73, 0.96 and 0.91, respectively. Pb, Cd, Hg, Mn, and Se showed a significant positive correlation between maternal blood and cord blood, with Spearman correlation coefficients of 0.397, 0.298, 0.698, 0.555, and 0.285 (all P values<0.001). Conclusion: Each element was commonly detected in maternal blood and cord blood. The TTE of Hg was the highest.

Transplacental Transfer of Per- and Polyfluoroalkyl Substances Identified in Paired Maternal and Cord Sera Using Suspect and Nontarget Screening

Novel per- and polyfluoroalkyl substances (PFASs) in various environmental media have attracted increasing attention; however, the information regarding PFASs exposure in pregnant women and fetuses is insufficient. In this study, we built and applied suspect and nontarget screening strategies based on the mass difference of the CF2, CF2O, and CH2CF2 units to select potential novel PFASs from 117 paired maternal and cord sera. In total, 10 legacy PFASs and 19 novel PFASs from 10 classes were identified to be above confidence levels 3, among which 14 were not previously reported in human serum. Novel PFASs accounted for a considerable percentage of total PFASs in pregnant women and can be transferred to fetuses at non-negligible concentrations (i.e., 27.9% and 30.3% of total PFAS intensities in maternal and cord sera, respectively). The transplacental transfer efficiency (TTE) of PFASs showed a U-shape trend in the series of perfluoroalkyl carboxylic acids, perfluoroalkyl sulfonic acids, and unsaturated perfluorinated alcohols. The TTE of novel PFASs is suggested to be structure-dependent, based on a flexible docking experiment. This study provides comprehensive TTE information on legacy and novel PFASs for the first time, and additional toxicity studies are needed to evaluate the risk of novel PFASs further.

Prevalence, Biotransformation, and Maternal Transfer of Synthetic Phenolic Antioxidants in Pregnant Women from South China.

Synthetic phenolic antioxidants (SPAs) have been identified as an emerging group of contaminants in recent years. However, there are significant gaps in our knowledge of human prenatal exposure to these synthetic chemicals. In this study, a set of eight SPAs and four major transformation products (TPs) were systematically analyzed in matched samples of maternal plasma, cord plasma, and placenta from a population of pregnant women. Five of the eight target SPAs and all four target TPs were frequently detected in the maternal-placental-fetal unit, indicating prenatal exposure to SPAs and the transfer of SPAs across the placenta. In the three matrices, 2,6-di-tert-butyl-hydroxytoluene (BHT), 2,4-di-tert-butylphenol (DBP), and 2,2'-methylenebis(4-methyl-6-tert-butylphenol) (AO 2246) were identified as the most abundant SPAs, while 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q) and 2,6-di-tert-butyl-4-hydroxy-4-methyl-2,5-cyclohexadienone (BHT-quinol) were identified as the predominant TPs of BHT. In the maternal plasma, concentrations of both BHT-Q and BHT-quinol were significantly correlated with BHT (p < 0.001), suggesting that the two TPs mainly originated from the biotransformation of BHT itself in pregnant women. The transplacental transfer efficiencies (TTEs) of the SPAs and TPs were structure-dependent and generally less than 1. Significantly higher TTEs for four target TPs than their parent BHT were identified. To our knowledge, this study provides the first evidence that SPAs and TPs transfer across the placenta in pregnant women.

Physico-chemical properties and gestational diabetes predict transplacental transfer and partitioning of perfluoroalkyl substances

BackgroundPer- and polyfluoroalkyl substances (PFASs) are a growing public health concern. Some longer chain PFASs bioaccumulate and many compounds persist in the environment for long time periods. Recent studies have established their ability to pass through placenta, yet data on the transplacental transfer efficiency and partitioning of short and long chain PFASs in blood matrices are limited. ObjectivesTo assess predictors of the partitioning of 17 PFAS compounds detected in the maternal serum, umbilical cord serum and whole cord blood samples from matched mother-newborn pairs from two Faroe Islands cohorts. MethodsWe examined 151 mother-newborn pairs from two successive Faroese birth cohorts. Cord:maternal serum (transplacental transfer) and serum:whole cord blood (blood partitioning) ratios were estimated for 17 PFAS compounds. We also examined the relationships of these ratios with maternal, newborns', and physico-chemical properties using multivariable regression analyses. ResultsModerate to high correlations were observed between maternal and cord serum PFAS concentrations (ρ: 0.41 to 0.95), indicating significant transfer of these compounds from the mother to the fetus. Median transplacental transfer ratios were generally below 1, except for perfluorooctane sulfonamide (FOSA), and ranged between 0.36 for perfluorodecanoate (PFDA) and perfluoroundecanoate (PFUnDA) and 1.21 for FOSA. Most PFASs exhibited a preference to the serum component of the blood, except FOSA and perfluoroheptanoate (PFHpA), with blood partitioning ratios ranging from 0.36 for FOSA to 2.75 for PFUnDA. Both the functional groups and carbon chain length of different PFASs were important predictors of transplacental transfer and blood partitioning. We observed a U-shaped relationship between transplacental transfer ratios and carbon chain length for perfluorocarboxylates and perfluorosulfonates. Importantly, gestational diabetes was also a strong predictor of transplacental transfer ratios, with significantly higher transfer in mothers with gestational diabetes. ConclusionsOur findings provide a better understanding of the transplacental transfer and blood partitioning of a large number of PFAS compounds. Results elucidate the importance of chemical structure for future risk assessments and choice of appropriate blood matrices for measurement of PFAS compounds.

Efficiency of maternal-fetal transfer of perfluoroalkyl and polyfluoroalkyl substances.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) can be transferred from a mother to her fetus during pregnancy and adversely affect fetal development. However, the efficiency and influencing factors of PFASs maternal-fetal transfer remain unclear. We measured the levels of six perfluoroalkylcarboxylates, three perfluoroalkylsulfonates, and one sulfonamide in 369 pairs of maternal and umbilical cord serum and examined the transplacental transfer efficiency (TTE) of PFASs by the functional group and carbon chain length in a prospective birth cohort in Shandong, China. All ten PFASs were detected in both maternal and umbilical cord serum in nearly all samples. Maternal and cord levels were closely correlated (the correlation coefficient [r] ranging from 0.485 to 0.908) in most PFASs except perfluorobutane sulfonic acid (PFBS) (r = 0.159). TTE was significantly affected by the functional group and carbon chain length. Compared to perfluoroalkylcarboxylates, perfluoroalkylsulfonates had a lower ratio of maternal to fetal transfer. A U-shaped relationship between carbon chain length and TTE was observed for perfluoroalkylcarboxylates while a monotonic descending trend was identified between TTE and the increasing carbon chain length for perfluoroalkylsulfonates. PFASs can readily pass through the placenta. The functional group and carbon chain length are important determinants for the TTE of PFASs.

Transplacental Transfer Efficiency and Blood Partitioning of Perfluoroalkyl Substances

Background: Recent studies have established the ability of perfluoroalkyl substances (PFASs) to pass through the placenta, however data on PFAS transfer efficiency and blood partitioning are limited.Aim: We evaluated transplacental transfer and blood partitioning of 16 PFASs detected in maternal serum, cord serum and cord whole blood, as well as the associations of mother-newborn characteristics with PFAS transfer efficiency and blood partitioning.Methods: We examined 151 mother-child pairs from two Faroese cohorts born in 1999-2001 and 2008-2009. Cord:maternal serum (transplacental transfer ratio [TTR]) and cord serum:whole blood (blood partitioning) ratio were estimated for 9 perfluorocarboxylates, 4 perfluorosulfonates and 3 precursor compounds. Multivariable regression analyses assessed the associations of potential predictors (i.e., cohort, maternal age, parity, gestational diabetes, sex and birthweight) with the ratios.Results: Correlations between maternal and cord serum concentrations were moderate to high for all PFASs (&amp;#961;: 0.41 to 0.95), indicating significant transfer from mother to fetus. Median TTRs ranged from 0.36 (PFDA and PFUnDA) to less than 1 for all PFASs, except FOSA (TTR: 1.21). All PFASs had higher concentrations in serum than whole blood, except FOSA and PFHpA, with partitioning ratios from 0.36 (FOSA) to 2.75 (PFUnDA). PFAS family and carbon chain length were important predictors of transfer and blood partitioning ratios, with U-shaped relationships seen between TTRs and carbon chain length. We also found significantly higher transplacental transfer to newborns of mothers diagnosed for gestational diabetes (adjusted ratio increases between 23% and 44% depending on PFAS).Conclusions: This study suggests that transplacental transfer and blood partitioning depends on PFAS family, carbon chain length and mother-newborn characteristics, such as gestational diabetes. These findings can improve PFAS exposure risk assessment in epidemiologic studies.

Noncanonical placental Fc receptors: What is their role in modulating transplacental transfer of maternal IgG?

The transplacental transfer of maternal Immunoglobulin G (IgG) to the fetus is critical for protection against infectious diseases in the first year of life [1]. Maternal protective IgG is transferred from the maternal to the fetal circulatory system via the placenta, and this process begins in the first trimester of pregnancy [2]. By 37–40 weeks of gestation, maternal passively acquired IgG concentrations in newborns can exceed maternal IgG serum levels in normal pregnancies [3–7]. Yet, the molecular mechanisms of transplacental transfer of maternal IgG remain poorly understood. In order to reach the fetal circulatory system, maternal IgG must traverse three distinct placental anatomical barriers: (1) the syncytiotrophoblast cell barrier, (2) the villous stroma containing placental fibroblasts and Hofbauer cells, and (3) fetal endothelial cells. It is well established that IgG crosses the syncytiotrophoblast by binding to the canonical IgG shuttle receptor: Fragment crystallizable (Fc) receptor neonatal (FcRn) [2, 8]. However, how maternal IgG traverses the subsequent placental barriers is not completely understood, as they do not express FcRn, yet recent RNAseq analyses have shown that Fcγ receptors, including FcγRIIIa, FcγRIIa, FcγRIIb, and FcγRI, are expressed in term placentas [9]. However, it should be cautioned that it is not yet known if these noncanonical placental FcRs play a role, if at all, in the transplacental transfer of maternal IgG. A deeper understanding of the molecular mechanism(s) of IgG binding to placentally expressed Fc receptors could be important (1) for the design of novel maternal IgG-based therapeutics and vaccines with optimal transplacental transfer efficiency, with the ultimate goal of increasing infant protection against congenital and neonatal infectious diseases, and (2) to optimize the Fc region of immunomodulatory IgG monoclonal antibody therapeutics for blunted transplacental transfer to potentially reduce the transplacental transport of maternal self-reactive IgG in women with autoimmune disorders.

2160 Does maternal schistosomiasis affect the humoral and cellular vaccine responses of infants?

OBJECTIVES/SPECIFIC AIMS: The aims of this study are 2-fold: (1) to determine if maternal schistosomiasis affects maternal immunity to tetanus and/or transplacental transfer of antitetanus toxoid (TT) immunoglobulin G (IgG) from mother to infant and (2) determine the influence of maternal schistosomiasis on infant BCG vaccine immunogenicity. METHODS/STUDY POPULATION: The study will utilize blood samples from a historic cohort of 100 mother-infant pairs from Kisumu, Kenya, a schistosomiasis-endemic area. For the first aim, we will evaluate maternal schistosomal circulating anodic antigen, which has improved sensitivity and specificity to detect active schistosomiasis from serum, and antisoluble egg antigen IgG positivity compared with quantitative maternal anti-TT IgG at delivery and anti-TT IgG cord blood to maternal blood ratio (cord:maternal ratio). For the second aim, we will evaluate association between maternal schistosomiasis as detected by circulating anodic antigen and antisoluble egg antigen IgG at delivery and infant BCG-specific Th1-cytokine positive CD4+ cells at 10 weeks following BCG vaccination at birth. RESULTS/ANTICIPATED RESULTS: We hypothesize that active maternal schistosomiasis will be associated with decreased maternal anti-TT IgG and reduced efficiency of transplacental transfer, as measured by infant cord blood to maternal blood ratio of anti-TT IgG. We also expect that maternal schistosomiasis will be associated with decreased infant immunogenicity to BCG vaccine. DISCUSSION/SIGNIFICANCE OF IMPACT: This is a formative study on infant vaccine immunity using laboratory methodology not previously applied. Understanding infant immunity in the setting of maternal schistosomiasis will inform vaccination strategies and tailor vaccine development in schistosome-endemic areas such as Kenya, where neither TB nor neonatal tetanus have been eradicated. Additionally, our results will inform public health policies to consider integration of antischistosomal agents in antenatal care.

Isomer-Specific Transplacental Efficiencies of Perfluoroalkyl Substances in Human Whole Blood

Data on isomer-specific transplacental transfer of perfluoroalkyl substances (PFASs) are very scarce. This study investigates transplacental transfer of 23 PFASs, including isomers of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS), by analyzing 63 paired maternal and cord whole blood samples collected in Hubei, China. Significant correlations (r = 0.311–0.888; p ≤ 0.013) were observed between the concentrations in maternal and cord blood for most PFASs, indicating that PFASs could be efficiently transported from mother to fetus. For perfluorocarboxylates, a U-shaped trend of transplacental transfer efficiencies (TTEs) with increasing carbon chain lengths was confirmed. For PFOA and PFOS branched isomers, TTEs generally increased as the branching point moved closer to the carboxyl or sulfonate moiety, and branched isomers transferred more efficiently than their linear isomers did. This is the first report of the TTEs of PFAS isomers based on human whole blood samples and the first calculatio...