Metabolites In Pregnant Women Research Articles

Pharmacokinetics and Transplacental Transfer of Fluoxetine Enantiomers and Their Metabolites in Pregnant Women.

Considering that fluoxetine (FLX) is used to treat depressive states during pregnancy and that it is a cytochrome P450 (CYP)2D6 inhibitor, which is involved in the metabolism of both of its enantiomers, this study aims to describe the enantioselective distribution and metabolism of FLX and of its metabolite norfluoxetine (NorFLX) following a single oral dose. Nine healthy pregnant women received 20mg FLX at 32weeks of gestation and later at the day of delivery. The apparent clearance of (S)-(+)-FLX (1.45 vs. 0.66L/hour/kg) and the area under the plasma concentration vs. time curve (AUC) of the (S)-(+)-NorFLX (AUC0-∞ 942.7 vs. 498.6nghour/mL) were higher (P<0.05) than those of the respective (R)-(-) enantiomers, indicating that the (S)-(+)-FLX enantiomer is preferentially metabolized to (S)-(+)-NorFLX. The placental transfer (umbilical vein/maternal vein) of FLX and NorFLX is low (30-40%), with the predominant transfer of (S)-(+)-FLX (44 vs. 33%). The distribution of the enantiomers of FLX and NorFLX to amniotic fluid is low (<10%).

Development of Highly Sensitive Analysis Method for Histamine and Metabolites in Pregnant Women’s Fingernail by UPLC-ESI-MS

In this study, a highly sensitive analysis method for the rapid detection of histamine (HA), imidazole-4-acetic acid (IAA) and 1-methylhistamine (MHA) in pregnant women's fingernails was developed using the ultra-performance liquid chromatography (UPLC) coupled with electrospray ionization tandem mass spectrometry (ESI-MS/MS). HA and MHA were connected with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F) as the derivation reagent for the first time. IAA was derivatized with 4-(N,N-dimethylaminosulfonyl)-7-piperazino-2,1,3-benzoxadiazole (DBD-PZ) successfully. The derivative mixtures were simultaneously separated within 8 min on an ACQUITY UPLCTM BEH C18 column (1.7 μm, 100 × 2.1 mm i.d.) by isocratic elution using a mixture of 20 mM HCOONH4 and CH3CN (82:18) as the mobile phase, and sensitively detected by selected reaction monitoring (SRM). The quantitative analysis of HA, IAA, and MHA are performed by SRM using the fragmentation transitions of m/z 337.2 → 292.1, 420.6 → 375.1 and 351.2 → 306.0 under the positive ESI mode. The calibration curves for HA, IAA and MHA are presented herein, and their correlation coefficient were found to be above 0.9998, the measured detection limit for derivatized histamine and metabolites ranged from 0.06 to 0.15 fmol, and the relative standard derivation of intra-day and inter-day assays was 6.3%. Furthermore, the mean recoveries (%) of the standards added to human fingernails were in the range of 90.2 - 100.5%. The validated method was successfully applied to analyze human fingernail samples from three pregnant women and three healthy non-pregnant women. To the best of our knowledge, this report about the detection of histamine and metabolites in the fingernails of pregnant women's fingernails is the first published.

Placental vitamin D metabolism and its associations with circulating vitamin D metabolites in pregnant women

Background: Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans.Objective: This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy.Design: Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk. Concentrations of placental and blood vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D metabolic pathway components were quantified. In addition, cultured human trophoblasts were incubated with 13C-cholecalciferol to examine the intracellular generation and secretion of vitamin D metabolites along with the regulation of target genes.Results: In placental tissue, 25-hydroxyvitamin D3 [25(OH)D3] was strongly correlated (r = 0.83, P < 0.001) with 24,25-dihydroxyvitamin D3 Moreover, these placental metabolites were strongly correlated (r ≤ 0.85, P ≤ 0.04) with their respective metabolites in maternal circulation. Positive associations (P ≤ 0.045) were also observed between placental mRNA abundance of vitamin D metabolic components and circulating vitamin D metabolites [i.e., LDL-related protein 2 (LRP2, also known as megalin) with 25(OH)D3 and the C3 epimer of 25(OH)D3 [3-epi-25(OH)D3]; cubilin (CUBN) with 25(OH)D3; 25-hydroxylase (CYP2R1) with 3-epi-25(OH)D3; 24-hydroxylase (CYP24A1) with 25(OH)D3, 3-epi-25(OH)D3, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]; and 1α-hydroxylase [(CYP27B1) with 3-epi-25(OH)D3 and 1,25(OH)2D3]. Notably, in vitro experiments with trophoblasts showed increased production and secretion of 25(OH)D3 and higher CYP24A1 gene transcript abundance in response to cholecalciferol treatment.Conclusions: The numerous associations of many of the placental biomarkers of vitamin D metabolism with circulating vitamin D metabolites among pregnant women [including a CYP27B1-associated increase in 1,25(OH)2D3] and the evidence of trophoblast production and secretion of vitamin D metabolites, especially 25(OH)D3, suggest that the placenta may play an active role in modulating the vitamin D metabolite profile in maternal circulation in human pregnancy. This trial was registered at clinicaltrials.gov as NCT03051867.

Flame retardants and their metabolites in the homes and urine of pregnant women residing in California (the CHAMACOS cohort)

Organophosphate flame retardants (PFRs), used in consumer products since the 1970s, persist in the environment. Restrictions on penta-polybrominated diphenyl ether (PBDE) flame retardants resulted in increased use of Firemaster® 550 (FM® 550), and the organophosphate triesters: tris(1,3- dichloro-2-propyl) phosphate (TDCIPP); tris(chloropropyl) phosphate (TCIPP); tris(2-chloroethyl) phosphate (TCEP); and triphenyl phosphate (TPHP). The objectives of this study were to (1) identify determinants of flame retardants (4 PFRs, PentaBDEs and FM® 550) in house dust, (2) measure urinary PFR metabolites in pregnant women, and (3) estimate health risks from PFR exposure. We measured flame retardants in house dust (n = 125) and metabolites in urine (n = 310) collected in 2000–2001 from Mexican American women participating in the CHAMACOS birth cohort study in California. We detected FM® 550 and PFRs, including two (TCEP and TDCIPP) known to the state of California to cause cancer, in most dust samples. The maximum TCEP and TDCIPP dust levels were among the highest ever reported although the median levels were generally lower compared to other U.S. cohorts. Metabolites of TDCIPP (BDCIPP: bis(1,3-dichloro-2-propyl) phosphate) and TPHP (DPHP: diphenyl phosphate) were detected in 78% and 79% of prenatal urine samples, respectively. We found a weak but positive correlation between TPHP in dust and DPHP in 124 paired prenatal urine samples (Spearman rho = 0.17; p = 0.06). These results provide information on PFR exposure and risk in pregnant women from the early 2000's and are also valuable to assess trends in exposure and risk given changing fire safety regulations and concomitant changes in chemical flame retardant use.

Prenatal Exposure to Glycol Ethers and Neurocognitive Abilities in 6-Year-Old Children: The PELAGIE Cohort Study.

Background:Glycol ethers (GE) are widely used organic solvents. Despite the potential neurotoxicity of several families of organic solvents, little is known about the impact of GE on the neurodevelopment of infants and children.Objectives:We investigated the relation between urinary concentrations of GE metabolites in pregnant women and neurocognitive abilities in their 6-year-old children in the PELAGIE mother–child cohort.Methods:Five GE metabolites were measured in first morning void urine samples of 204 French pregnant women in early pregnancy (< 19 weeks of gestation). Psychologists assessed the neurocognitive abilities of their 6-year-old children with the Wechsler Intelligence Scale for Children IV (WISC) and the Developmental Neuropsychological Assessment (NEPSY). We analyzed the results with linear (WISC) and Poisson regression models (NEPSY), adjusted for potential confounders, including child’s stimulation at home.Results:GE metabolites were detected in 90–100% of maternal urine samples. The WISC Verbal Comprehension score was significantly lower for children with the highest tertile of urinary phenoxyacetic acid (PhAA) [β (third vs. first tertile) = –6.53; 95% CI: –11.44, –1.62]. Similarly, the NEPSY Design Copying subtest score was lower in those with the highest tertile of urinary ethoxyacetic acid (EAA) [β (third vs. first tertile) = –0.11; 95% CI: –0.21, 0.00]. The other GE metabolites we studied were not significantly associated with WISC or NEPSY scores.Conclusions:Prenatal urine concentrations of two GE metabolites were associated with lower WISC Verbal Comprehension Index scores and NEPSY Design Copying subscale scores, respectively, at age 6 years. PhAA is the primary metabolite of 2-phenoxyethanol (EGPhE), which is commonly found in cosmetics, and precursors of EAA are frequently used in cleaning agents. Additional research is needed to confirm our findings and further explore potential effects of prenatal GE exposures on neurocognitive performance in children.Citation:Béranger R, Garlantézec R, Le Maner-Idrissi G, Lacroix A, Rouget F, Trowbridge J, Warembourg C, Monfort C, Le Gléau F, Jourdin M, Multigner L, Cordier S, Chevrier C. 2017. Prenatal exposure to glycol ethers and neurocognitive abilities in 6-year-old children: the PELAGIE cohort study. Environ Health Perspect 125:684–690; http://dx.doi.org/10.1289/EHP39

Temporal Trends in Phthalate Exposures in the Swedish pregnancy cohort

INTRODUCTION: Epidemiological studies have found that the general population is exposed to chemicals that may interact with the endocrine system in humans and animals, so called endocrine disrupting chemicals (EDCs). In the SELMA study we investigate the importance of pre- and post-natal exposure of EDCs and life style factors for development of chronic diseases and development in offspring in Sweden. Phthalates are a group of EDCs used in plastics and numerous consumer products. Temporal trends in urinary levels of phthalate metabolites in pregnant women were examined. METHODS: Metabolites of five phthalate (DEP, DBP, BBzP, DEHP and DiNP) were analyzed by liquid chromatography tandem mass spectrometry in urine from 2,356 pregnant women in the SELMA study. The samples were collected at their first visit (week 10) to the public antenatal care centers in Sweden during the period of September 2007 to April 2010. The samples were analyzed in a randomized order. Least square geometric means (LSGM) of phthalate metabolites were compared between different SELMA sampling years with covariates included. RESULTS: Ten phthalate metabolites were 100% detectable in all SELMA subjects. All DEHP metabolites showed a decreasing trend (p&lt;0.01) over the sampling period (2007-2010), 2010 LSGM concentrations decreased 7% when compared with 2007. Also, the DEP metabolite decreased (10%). For DiNP phthalates, a steady upward temporal trend was found where LSGM concentration of ∑DiNP metabolites increased significantly between 2007 and 2010. LSGM concentrations increased 4.1% (p=0.15) in 2008, 7.5% (p=0.011) in 2009, and 19% (p=0.0002) when compared with 2007. Conclusions: Our analysis from a large sample suggests that Swedish exposure to some phthalates – measured as their metabolites in urine of pregnant women – has changed during a 2.5 year period from 2007 to 2010. We found that DEHP and to a lower degree DEP metabolite levels have decreased while DiNP metabolite levels have increased.

Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine.

Background. Status of folic acid use in pregnant women of the hilly regions in North India was little known. This study was carried out to assess the folic acid use and estimate folate metabolites in pregnant women of this region. Materials and Methods. This cross-sectional study is comprised of 76 pregnant women, whose folic acid supplementation was assessed by a questionnaire and serum levels of homocysteine, tetrahydrofolic acid (THFA), and dihydrofolate reductase (DHFR) were estimated using Enzyme Linked Immunoassays. Results. The study data revealed awareness of folic acid use during pregnancy was present in 46.1% and 23.7% were taking folic acid supplements. The study depicted that there was no statistically significant difference between serum levels of THFA and DHFR in pregnant women with and without folic acid supplements (p = 0.790). Hyperhomocysteinemia was present in 15.78% of the participants. Conclusion. Less awareness about folic acid supplementation and low use of folic acid by pregnant women were observed in this region. Sufficient dietary ingestion may suffice for the escalated requirements in pregnancy, but since this cannot be ensured, hence folic acid supplementation should be made as an integral part of education and reproductive health programs for its better metabolic use, growth, and development of fetus.

Associations between urinary phthalate metabolites and biomarkers of inflammation and oxidative stress in pregnant women

Background: Phthalate exposure is prevalent and associated with an array of adverse health effects. We hypothesized that these relationships may be mediated by phthalate-induced increases in systemic levels of inflammation and oxidative stress. In this study we examine the relationship between phthalate exposure and changes in biomarkers of inflammation and oxidative stress during pregnancy. Methods: Pregnant women recruited in the first trimester provided urine and plasma samples at medians of 10, 18, and 26 weeks gestation. C-reactive protein (CRP) and cytokines IL- 1?, IL-6, IL-10, and TNF-? were measured in plasma as markers of inflammation, and 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane (8-Iso) in urine were markers of oxidative stress. As an indicator of exposure, phthalate metabolites were measured in urine samples and levels were averaged across pregnancy. Results: Crude analysis between biomarkers and phthalate levels standardized for specific gravity showed significant positive correlations between CRP and mono-benzylbutyl phthalate (MBzP), mono-butyl phthalate (MBP), and mono-ethyl phthalate (MEP). Correlations were stronger with oxidative stress biomarkers for the same metabolites as well as mono-isobutyl phthalate (MiBP) and mono-carboxypropyl phthalate (MCPP). In models adjusting for specific gravity, maternal age, race/ethnicity, and education level associations with CRP and MBzP remained significant. Relationships between oxidative stress markers and MBzP, MBP, MiBP, MEP, and MCPP retained significance as well. Associations between phthalate metabolites and cytokines were spurious in both crude and adjusted analyses. Conclusions: Markers of inflammation (CRP) and oxidative stress (8-OHdG and 8-Iso) are associated with urinary phthalate metabolites in pregnant women which has relevance for understanding phthalate relationships with reproductive outcomes.

Impact of low-level gestational exposure to organophosphate pesticides on neurobehavior in early infancy: a prospective study

BackgroundNational data suggest widespread gestational exposure to organophosphate pesticides (OPs) based on the detection of OP metabolites in the urine of pregnant women. Associations with early infant neurobehavior are largely understudied, with only two studies reporting abnormal reflexes in newborns in association with gestational exposure to OPs. Our objective was to utilize biological markers of OP metabolites in pregnant women and a comprehensive assessment of infant neurobehavior to determine the association of gestational exposure to OPs with neurobehavioral outcomes during early infancy.MethodsAmong a cohort of 350 mother/infant pairs, we measured six common dialkylphosphate metabolites of OP pesticides in maternal urine, at two times during pregnancy (16 w & 26 w gestation), then calculated aggregate concentrations of diethylphosphate, dimethylphosphate, and total dialkyphosphate metabolites. We measured infant neurobehavior at about five weeks of age using the NICU Network Neurobehavioral Scale (NNNS), a comprehensive assessment of neurobehavior in young infants. Analyses of associations between gestational exposure to OPs and neurobehavior at five weeks included multiple linear and logistic regression.ResultsAfter adjustment for covariates, higher creatinine-corrected urinary concentrations of diethylphosphate metabolites were associated with improved attention and reduced lethargy and hypotonia in young infants. Higher creatinine-corrected urinary concentrations of total dialkylphosphate metabolites were associated with fewer signs of autonomic stress. Women who were white, married, had advanced education, and reported more frequent consumption of fresh fruits and vegetables had higher concentrations of OP metabolites during pregnancy.ConclusionsIn this sample of pregnant women whose urinary concentrations of dialkylphosphate metabolites are representative of national exposure levels, we found no detrimental effects of gestational exposure to OPs on neurobehavioral outcomes among young infants. These results are important as they suggest there may be minimal to no detectable adverse impact of low level prenatal OP exposure on the neurobehavior of young infants.

EHP Paper of the Year, 2012

Environmental Health Perspectives (EHP) established the Paper of the Year Award in 2008 to recognize high-quality papers published in the journal (Tilson 2008). Starting in 2011, EHP decided to recognize two papers each year (Tilson 2011). The EHP Classic Paper of the Year is the research article, commentary, or review that is the most highly cited over the preceding 60 months. The winner of the 2012 EHP Classic Paper of the Year, announced last July, was “Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004” by Antonia M. Calafat, Xiaoyun Ye, Lee-Yang Wong, John A. Reidy, and the late Larry L. Needham of the Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention (Tilson 2012). The second paper to be recognized each year is the EHP Paper of the Year. This award recognizes the most highly cited paper published during the preceding year. Both awards are subject to the approval of the EHP Board of Associate Editors. In this issue, EHP is pleased to announce that the 2012 Paper of the Year award will be shared by three papers published in the same issue: “Prenatal Exposure to Organophosphates, Paraoxonase 1, and Cognitive Development in Childhood” by Stephanie M. Engel, James Wetmur, Jia Chen, Chenbo Zhu, Dana Boyd Barr, Richard L. Canfield, and Mary S. Wolff (Engel et al. 2011); “Prenatal Exposure to Organophosphate Pesticides and IQ in 7-Year-Old Children” by Maryse F. Bouchard, Jonathan Chevrier, Kim G. Harley, Katherine Kogut, Michelle Vedar, Norma Calderon, Celina Trujillo, Caroline Johnson, Asa Bradman, Dana Boyd Barr, and Brenda Eskenazi (Bouchard et al. 2011); and “Seven-Year Neurodevelopmental Scores and Prenatal Exposure to Chlorpyrifos, a Common Agricultural Pesticide” by Virginia Rauh, Srikesh Arunajadai, Megan Horton, Frederica Perera, Lori Hoepner, Dana B. Barr, and Robin Whyatt (Rauh et al. 2011). The three studies were conducted at the Mount Sinai School of Medicine (Engel et al. 2011); the University of California, Berkeley, School of Public Health (Bouchard et al. 2011); and the Mailman School of Public Health at Columbia University (Rauh et al. 2011). The Berkeley and Mount Sinai investigators measured organophosphate (OP) pesticide metabolites in pregnant women’s urine, and the Columbia investigators measured the OP pesticide chlorpyrifos in umbilical cord blood. Children of these mothers were administered intelligence tests when they were 6–9 years of age at Mount Sinai and at 7 years of age at Berkeley and Columbia. All three studies reported associations between prenatal OP pesticide exposures and adverse effects on cognitive function that continued into early childhood. The fact that three research groups reached such similar conclusions independently adds considerable support to the validity of the findings. EHP congratulates all the authors of these papers for their contribution to the environmental health science literature. These findings underscore the need to continue monitoring levels of exposure to pesticides in vulnerable populations and to study the under-lying biological changes associated with alterations of cognitive function following developmental exposure to environmental chemicals.

Urinary pyrethroid metabolites among pregnant women in an agricultural area of the Province of Jiangsu, China

Pyrethroid pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Of particular concern is exposure of pregnant women and their fetuses because little is known about the potential developmental hazards of such exposure. Several studies have detected internal pyrethroid exposure in urine both in adults and children, but few published data are available on metabolites in pregnant women. The present paper provides data on pyrethroid pesticides exposure based on questionnaire items and measurement of maternal urinary metabolite levels among 1149 pregnant women living in agricultural area of Jiangsu Province, China in 2009-2010, none of which reported occupational exposure to pyrethroid insecticides during pregnancy. To assess exposure to pyrethroid pesticides, urine specimens were analyzed for three main metabolites of 3-phenoxybenzoic acid (3-PBA), cis-and-trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-DCCA and trans-DCCA) using a gas chromatography-mass spectrometry method. The limits of detection for three pyrethroid metabolites were 0.1μg/L. All pyrethroid metabolites were found in more than 94.0% of the urine samples. Median unadjusted and creatinine-adjusted values for urinary pyrethroid metabolites in these females were 1.01μg/L and 1.55μg/g Cre for 3-PBA, 0.44μg/L and 0.69μg/g Cre for cis-DCCA, 1.17μg/L and 1.86μg/g Cre for trans-DCCA, respectively. About half (45.5%) of women reported that they or family members had applied commercially available indoor insecticides during pregnancy. Both the questionnaire and laboratory data revealed that exposure to pyrethroid pesticides was considerably widespread in our subjects. The median values of urinary metabolites in the present study were about 4-10 times higher as those of general population from the developed countries. Interestingly, we found there was a temporal season variation tendency in different months. Especially, the levels of urinary metabolites in summer were significant higher than those in winter. These data indicated the need to assess the potential adverse effects of pyrethroid pesticides exposure on fetuses and infants in order to take adequate measures to protect pregnant women from pesticide exposures during pregnancy.

Bisphenol-A and phthalates contamination of urine samples by catheters in the Elfe pilot study: Implications for large-scale biomonitoring studies

Exposure to phthalates and Bisphenol A could cause developmental and reproductive toxicity. This study provides a first assessment of these exposures for more than 250 French pregnant women. The median concentrations of total and free Bisphenol A in urine were similar to those in other studies except the highest concentrations (5% of women had total and free Bisphenol A >50 μg/L). Our study highlights high levels of Di-(2-ethylhexyl)-phthalate metabolites in pregnant women, suggesting recent exposure, probably in hospital. Differences between types of delivery (caesarean vs. natural) support this hypothesis. This is a significant implication for large-scale biomonitoring studies among this population.

Prenatal and Postnatal Exposure to Phthalates and the Relation to Steroid Hormone and Gender Role Behavior in Children

PP-31-092 Background/Aims: Phthalates exposure was found associated with decreased anogenital index in male newborns and reduced masculine play boys. It is hypothesized that sex hormone might be altered and gender role behavior changed in relation to phthalates exposure. Methods: We investigate the relation of steroid hormones and pre-school activities inventory to phthalate metabolites in pregnant women and their children in a perspective cohort during 2001–2009 in central Taiwan. In all, 11 phthalate metabolites representing the exposure to 5 commonly used phthalates (Di(2-ethylhexyl)phthalate [DEHP], DiBP, DnBP, BP, and DiNP) were measured in urine, serum, and human milk by fully automated LC-LC/MS-MS-system. Steroid hormones were analyzed in maternal and children serum using radioimmunoassay. Results: DEHP metabolite levels in pregnant women urine were significantly correlated with their corresponding cord blood. Phthalate exposure was associated with decreased testosterone (TT) concentrations at the years of 0 (ie, cord cx-MiNP and cord TT: spearman correlation r = −0.49, P < 0.05, respectively). Postnatal exposure to DEHP was associated with decreased TT and pre-school activities inventory scores in girls at the age of 5 years, indicating stereotyped feminine toys and activities, with adjustment for gender, education of the major caretaker, and elder brother or sisters. Conclusion: It is firstly reported that TT levels decreased with increasing phthalates exposure consistently in the young children at the ages of 0, 2, and 5 years. Transplacental exposure of phthalates and effect of steroid hormones are established. The feminine role might associate partly with the decreased TT. Postnatal exposure to phthalates is also important for the changes in hormone and behavior.

Phthalate exposure in pregnant women and their children in central Taiwan

Phthalate exposure was found to be associated with endocrine disruption, respiratory effects, reproductive and developmental toxicity. The intensive use of plastics may be increasing the exposure to phthalates in Taiwanese population, particularly for young children. We studied phthalate metabolites in pregnant women and their newborns in a prospective cohort from a medical center in Central Taiwan. One hundred maternal urine samples and 30 paired cord blood and milk samples were randomly selected from all of participants (430 pregnant women). Eleven phthalate metabolites (MEHP, 5OH-MEHP, 2cx-MEHP, 5cx-MEPP, 5oxo-MEHP, MiBP, MnBP, MBzP, OH-MiNP, oxo-MiNP, and cx-MiNP) representing the exposure to five commonly used phthalates (DEHP, di-isobutyl phthalate (DiBP), DnBP, BBP, DiNP) were measured in urine of pregnant women, cord serum and breast milk after delivery, and in urine of their children. Exposure was estimated with excretion factors and correlation among metabolites of the same parent compound. Thirty and 59 urinary samples from 2 and 5 years-old children were randomly selected from 185 children successfully followed. Total urinary phthalate metabolite concentration (geometric mean, μg L −1) was found to be higher in 2-years-olds (398.6) and 5-years-olds (333.7) than pregnant women (205.2). Metabolites in urine are mainly from DEHP. The proportion of DiNP metabolites was higher in children urine (4.39 and 8.31%, ages 2 and 5) than in adults (0.83%) ( p < 0.01). Compared to urinary levels, phthalate metabolite levels are low in cord blood (37.45) and milk (14.90). DEHP metabolite levels in women’s urine and their corresponding cord blood are significantly correlated. Compared to other populations in the world, DEHP derived metabolites in maternal urine were higher, while phthalate metabolite levels in milk and cord blood were similar. The level of phthalate metabolites in milk and cord blood were comparable to those found in other populations. Further studies of health effects related to DEHP and DiNP exposure are necessary for the children.

Organophosphate Pesticide Exposure and Attention in Young Mexican-American Children: The CHAMACOS Study

BackgroundExposure to organophosphate (OP) pesticides, well-known neurotoxicants, has been associated with neurobehavioral deficits in children.ObjectivesWe investigated whether OP exposure, as measured by urinary dialkyl phosphate (DAP) metabolites in pregnant women and their children, was associated with attention-related outcomes among Mexican-American children living in an agricultural region of California.MethodsChildren were assessed at ages 3.5 years (n = 331) and 5 years (n = 323). Mothers completed the Child Behavior Checklist (CBCL). We administered the NEPSY-II visual attention subtest to children at 3.5 years and Conners’ Kiddie Continuous Performance Test (K-CPT) at 5 years. The K-CPT yielded a standardized attention deficit/hyperactivity disorder (ADHD) Confidence Index score. Psychometricians scored behavior of the 5-year-olds during testing using the Hillside Behavior Rating Scale.ResultsPrenatal DAPs (nanomoles per liter) were nonsignificantly associated with maternal report of attention problems and ADHD at age 3.5 years but were significantly related at age 5 years [CBCL attention problems: β = 0.7 points; 95% confidence interval (CI), 0.2–1.2; ADHD: β = 1.3; 95% CI, 0.4–2.1]. Prenatal DAPs were associated with scores on the K-CPT ADHD Confidence Index > 70th percentile [odds ratio (OR) = 5.1; 95% CI, 1.7–15.7] and with a composite ADHD indicator of the various measures (OR = 3.5; 95% CI, 1.1–10.7). Some outcomes exhibited evidence of effect modification by sex, with associations found only among boys. There was also limited evidence of associations between child DAPs and attention.ConclusionsIn utero DAPs and, to a lesser extent, postnatal DAPs were associated adversely with attention as assessed by maternal report, psychometrician observation, and direct assessment. These associations were somewhat stronger at 5 years than at 3.5 years and were stronger in boys.

Relationships between gene polymorphisms of folate-related proteins and vitamins and metabolites in pregnant women and neonates

Background The methylenetetrahydrofolate reductase (MTHFR), glutamate carboxypeptidase II (GCPII) and reduced folate carrier (RFC1) gene polymorphisms were associated with folate status. We investigated the effects of these polymorphisms on serum folate (SF) and folate-related metabolites in mothers and their neonates. Methods Cobalamin (Cbl), SF, total homocysteine (tHcy), methylmalonic acid (MMA), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured in 275 healthy women and their neonates. MTHFR C677T, GCPII C1561T and RFC1 A80G polymorphisms were determined by PCR-RFLP. Results Maternal tHcy was affected individually by MTHFR C677T and GCPII C1561T polymorphisms and by combined genotypes MTHFR 677TT/ GCPII 1561CC and MTHFR 677TT/ RFC1 80AG. The MTHFR and RFC1 polymorphisms were not associated with variations in vitamins or SAM, SAH and MMA in neonates. Neonatal tHcy was predicted directly by maternal tHcy and inversely by maternal SF, neonatal Cbl and neonatal RFC1 80G allele (AG+GG genotypes). Maternal MMA and SAM/SAH were predicted by creatinine and Cbl, respectively. Neonatal MMA was predicted by maternal MMA and GCPII 1561T allele (CT+TT genotypes) and by neonatal Cbl. Conclusions Maternal tHcy was affected by MTHFR C677T, RFC1 A80G and GCPII C1561T polymorphisms. Maternal GCPII C1561T variant was associated with neonatal MMA. Neonatal RFC1 A80G polymorphism influenced tHcy in neonates.

Characterization of Phthalate Exposure among Pregnant Women Assessed by Repeat Air and Urine Samples

BackgroundAlthough urinary concentrations of phthalate metabolites are frequently used as biomarkers in epidemiologic studies, variability during pregnancy has not been characterized.MethodsWe measured phthalate metabolite concentrations in spot urine samples collected from 246 pregnant Dominican and African-American women. Twenty-eight women had repeat urine samples collected over a 6-week period. We also analyzed 48-hr personal air samples (n = 96 women) and repeated indoor air samples (n = 32 homes) for five phthalate diesters. Mixed-effects models were fit to evaluate reproducibility via intraclass correlation coefficients (ICC). We evaluated the sensitivity and specificity of using a single specimen versus repeat samples to classify a woman’s exposure in the low or high category.ResultsPhthalates were detected in 85–100% of air and urine samples. ICCs for the unadjusted urinary metabolite concentrations ranged from 0.30 for mono-ethyl phthalate to 0.66 for monobenzyl phthalate. For indoor air, ICCs ranged from 0.48 [di-2-ethylhexyl phthalate (DEHP)] to 0.83 [butylbenzyl phthalate (BBzP)]. Air levels of phthalate diesters correlated with their respective urinary metabolite concentrations for BBzP (r = 0.71), di-isobutyl phthalate (r = 0.44), and diethyl phthalate (DEP; r = 0.39). In women sampled late in pregnancy, specific gravity appeared to be more effective than creatinine in adjusting for urine dilution.ConclusionsUrinary concentrations of DEP and DEHP metabolites in pregnant women showed lower reproducibility than metabolites for di-n-butyl phthalate and BBzP. A single indoor air sample may be sufficient to characterize phthalate exposure in the home, whereas urinary phthalate biomarkers should be sampled longitudinally during pregnancy to minimize exposure misclassification.

Urinary Phenol Metabolites Among Pregnant Women

ISEE-369 Objective: Phenols and their metabolites are frequently detected in human biological fluids, suggesting prevalent exposure to the parent environmental agents. Little information is available regarding these chemicals with respect to variability in their concentrations and their relationships with genetic susceptibility, age, and socioeconomic factors. We characterized phenols in urine and associations with the UDP-glucuronosyltransferase 2B7 (UGT2B7) His268Tyr polymorphism and population characteristics as predictors of their concentrations. Material and Methods: Nine phenolic metabolites were measured in 367 urine samples from pregnant women in a New York City cohort. Multivariate analyses were conducted to identify predictors of phenols, including genetics, ethnicity, socioeconomic status, and use of consumer products in relation to metabolite concentrations. Results: Bisphenol A (BPA), 2-hydroxy-4-methoxybenzophenone, triclosan, and 2,4- and 2,5-dichlorophenol (DCP) were detected in at least 78% of samples. Concentrations of 2,5-DCP (median 52.9 μg/L) were above the 75th percentile of women in NHANES (1999–2000), with an adjusted geometric mean of 165 μg/L for mothball users. Differences by race/ethnicity were seen in 2,4-DCP, 2,5-DCP, and 4-tert-octylphenol concentrations. UGT2B7 Tyr268 allele carriers had lower BPA and triclosan metabolite urinary concentrations than those who were not carriers. Conclusions: This study is the first systematic evaluation of phenolic metabolites in pregnant women. Five of the 9 metabolites were detected frequently. Human UGT2B7 was seen for the first time to participate in metabolism of 2 of these chemicals.

Elevated amniotic fluid nitric oxide levels of metabolites in pregnant women with intraamniotic infection

Elevated amniotic fluid nitric oxide levels of metabolites in pregnant women with intraamniotic infection