Antidepressants use during pregnancy and child psychomotor, cognitive and language development at 2 years of age-Results from the 3D Cohort Study.

Introduction: Approximately 5.5% of pregnant women take antidepressants. Studies on prenatal exposure to antidepressants reported no association with child cognition, and inconsistent results with motor function and language development. A limitation has been the failure to adjust for prenatal maternal distress. Objectives: Assess the associations between prenatal exposure to antidepressants and child development at age two, while adjusting for maternal depressive symptoms and stress during pregnancy. Explore indirect effects through birth complications and consider sex-specific associations. Methods: This is an ancillary study of the 3D (Design Develop, Discover) Study initiated during pregnancy. Data on antidepressants were collected through medication logs spanning the entire pregnancy. Depressive symptoms and stress were assessed during pregnancy by self-reported questionnaires, motor and cognitive development with the Bayley Scales of Infant and Toddler Development (BSID-III), and language development with the MacArthur Communicative Development Inventories at age 2. Multiple linear regressions were used to assess the associations between exposure and developmental outcomes. Mediation models were used to assess indirect effects. Interaction terms were introduced to assess sex-specific associations. Results: 1,489 mother-child dyads were included, of whom 61 (4.1%) reported prenatal antidepressant use. Prenatal exposure was negatively associated with motor development (B = -0.91, 95% CI -1.73, -0.09 for fine motor, B = -0.89, 95% CI -1.81, 0.02 for gross motor), but not with cognitive (B = -0.53, 95% CI -1.82, 0.72) and language (B = 4.13, 95% CI -3.72, 11.89) development. Adjusting for maternal prenatal distress only slightly modified these associations. No indirect effect or differential effect according to child sex were found. Conclusion: This study supports evidence of a negative association between prenatal exposure to antidepressants and motor development at age two, after adjusting for maternal distress, but the effect size remains very small, with about only one BSID-III point lower in average.

In Utero Exposure to Caffeine and Acetaminophen, the Gut Microbiome, and Neurodevelopmental Outcomes: A Prospective Birth Cohort Study.

Pregnant individuals are exposed to acetaminophen and caffeine, but it is unknown how these exposures interact with the developing gut microbiome. We aimed to determine whether acetaminophen and/or caffeine relate to the childhood gut microbiome and whether features of the gut microbiome alter the relationship between acetaminophen/caffeine and neurodevelopment. Forty-nine and 85 participants provided meconium and stool samples at 6-7, respectively, for exposure and microbiome assessment. Fecal acetaminophen and caffeine concentrations were quantified, and fecal DNA underwent metagenomic sequencing. Caregivers and study staff assessed the participants' motor and cognitive development using standardized scales. Prenatal exposures had stronger associations with the childhood microbiome than concurrent exposures. Prenatal acetaminophen exposure was associated with a trend of lower gut bacterial diversity in childhood [ß = -0.17 Shannon Index, 95% CI: (-0.31, -0.04)] and was marginally associated with differences in the relative abundances of features of the gut microbiome at the phylum (Firmicutes, Actinobacteria) and gene pathway levels. Among the participants with a higher relative abundance of Proteobacteria, prenatal exposure to acetaminophen and caffeine was associated with lower scores on WISC-IV subscales. Acetaminophen during bacterial colonization of the naïve gut is associated with lasting alterations in childhood microbiome composition. Future studies may inform our understanding of downstream health effects.

The relationship between persistent organic pollutants and Attention Deficit Hyperactivity Disorder phenotypes: Evidence from task-based neural activity in an observational study of a community sample of Canadian mother-child dyads.

BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs), widespread in North America, is associated with increased Attention Deficit/Hyperactivity Disorder (ADHD) symptoms and may be a modifiable risk for ADHD phenotypes. However, the effects of moderate exposure to POPs on task-based inhibitory control performance, related brain function, and ADHD-related symptoms remain unknown, limiting our ability to develop interventions targeting the neural impact of common levels of exposure. OBJECTIVES: The goal of this study was to examine the association between prenatal POP exposure and inhibitory control performance, neural correlates of inhibitory control and ADHD-related symptoms. METHODS: Prospective data was gathered in an observational study of Canadian mother-child dyads, with moderate exposure to POPs, including polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as part of the GESTation and the Environment (GESTE) cohort in Sherbrooke, Quebec, Canada. The sample included 87 eligible children, 46 with maternal plasma samples, functional magnetic resonance imaging (fMRI) data of Simon task performance at 9-11 years, and parental report of clinical symptoms via the Behavioral Assessment System for Children 3 (BASC-3). Simon task performance was probed via drift diffusion modeling, and parameter estimates were related to POP exposure. Simon task-based fMRI data was modeled to examine the difference in incongruent vs congruent trials in regions of interest (ROIs) identified by meta analysis. RESULTS: Of the 46 participants with complete data, 29 were male, and mean age was 10.42 ± 0.55 years. Increased POP exposure was associated with reduced accuracy (e.g. PCB molar sum rate ratio = 0.95; 95% CI [0.90, 0.99]), drift rate (e.g. for PCB molar sum ß = -0.42; 95% CI [-0.77, -0.07]), and task-related brain activity (e.g. in inferior frontal cortex for PCB molar sum ß = -0.35; 95% CI [-0.69, -0.02]), and increased ADHD symptoms (e.g. hyperactivity PCB molar sum ß = 2.35; 95%CI [0.17, 4.53]), supporting the possibility that prenatal exposure to POPs is a modifiable risk for ADHD phenotypes. DISCUSSION: We showed that exposure to POPs is related to task-based changes in neural activity in brain regions important for inhibitory control, suggesting a biological mechanism underlying previously documented associations between POPs and neurobehavioral deficits found in ADHD phenotypes.

Pregnancy and Neonatal Outcomes With Levothyroxine Treatment in Women With Subclinical Hypothyroidism Based on New Diagnostic Criteria: A Systematic Review and Meta-Analysis.

Background: Subclinical hypothyroidism (SCH) during pregnancy has been associated with multiple adverse maternal and neonatal outcomes. However, the potential benefits of levothyroxine (LT4) supplementation remain controversial. Variations across studies in diagnostic criteria for SCH may, in part, explain the divergent findings on the subject. This study aimed to assess the effect of LT4 treatment on pregnancy and neonatal outcomes among pregnant women who were diagnosed as SCH based on the most recent diagnostic criteria. Methods: We conducted a systematic review and meta-analysis of the literature published from inception to January 2020. The search strategy targeted the studies on pregnancy and neonatal outcomes following LT4 treatment in women with SCH based on 2017 American Thyroid Association diagnostic criteria. Pooled effect sizes were estimated using fixed and random effect models, according to the absence or presence of heterogeneity which was assessed using the I-squared statistic. Sources of heterogeneity and the stability of results were evaluated through sensitivity analysis. Results: Of the 2781 identified references, 306 full-text articles were screened for eligibility. Finally, 6 studies including a total of 7955 participants were retained for analysis. Summary effect estimates indicated that pregnant women with SCH treated with LT4 had a lower risk of pregnancy loss [odds ratio (OR) = 0.55, 95% confidence interval (CI): 0.43-0.71], preterm birth (OR=0.63, 95% CI: 0.41-0.98) and gestational hypertension (OR = 0.78, 95% CI: 0.63-0.97) than those in control group. Conclusion: LT4 treatment in pregnant women with SCH may reduce the risk of pregnancy loss, preterm delivery and gestational hypertension.

In Utero Exposure to Persistent Organic Pollutants and Childhood Lipid Levels.

Animal studies have shown that developmental exposures to polybrominated diphenyl ethers (PBDE) permanently affect blood/liver balance of lipids. No human study has evaluated associations between in utero exposures to persistent organic pollutants (POPs) and later life lipid metabolism. In this pilot, maternal plasma levels of PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) and polychlorinated biphenyls (PCB-138, PCB-153, and PCB-180) were determined at delivery in participants of GESTation and Environment (GESTE) cohort. Total cholesterol (TCh), triglycerides (TG), low- and high-density lipoproteins (LDL-C and HDL-C), total lipids (TL), and PBDEs were determined in serum of 147 children at ages 6-7. General linear regression was used to estimate the relationship between maternal POPs and child lipid levels with adjustment for potential confounders, and adjustment for childhood POPs. In utero BDE-99 was associated with lower childhood levels of TG (p = 0.003), and non-significantly with HDL-C (p = 0.06) and TL (p = 0.07). Maternal PCB-138 was associated with lower childhood levels of TG (p = 0.04), LDL-C (p = 0.04), and TL (p = 0.02). Our data indicate that in utero exposures to POPs may be associated with long lasting decrease in circulating lipids in children, suggesting increased lipid accumulation in the liver, a mechanism involved in NAFLD development, consistent with previously reported animal data.

The association between prenatal concentrations of polybrominated diphenyl ether and child cognitive and psychomotor function.

Previous studies suggest a negative association between prenatal polybrominated diphenyl ethers (PBDEs) exposure and child cognitive and psychomotor development. However, the timing of the relationship between PBDE exposure and neurodevelopment is still unclear. We examined the association between PBDE concentration at two different prenatal times (early and late pregnancy) and cognitive function in children 6-8 years of age. METHODS: Eight hundred pregnant women were recruited between 2007 and 2009 from Sherbrooke, Canada. Four PBDE congeners (BDE-47, -99, -100, and -153) were measured in maternal plasma samples collected during early pregnancy (12 weeks of gestation) and at delivery. At 6-8 years of age, 355 children completed a series of subtests spanning multiple neuropsychologic domains: verbal and memory skills were measured using the Wechsler Intelligence Scale for Children, Fourth Edition; visuospatial processing using both Wechsler Intelligence Scale for Children, Fourth Edition and Neuropsychological Assessment second edition; and attention was assessed through the Test of Everyday Attention for Children. Additionally, parents completed subtests from the Developmental Coordination Disorder Questionnaire to measure child motor control. We used linear regression and quantile g-computation models to estimate associations of PBDE congener concentrations and psychologic test scores. RESULTS: In our models, no significant associations were detected between PBDE mixture and any of the child psychologic scores. BDE-99 concentration at delivery was nominally associated with higher scores on short-term and working memory while a decrease in spatial perception and reasoning was nominally associated with higher BDE-100 concentration at delivery. CONCLUSION: Overall, our results did not show a significant association between PBDEs and child cognitive and motor development.

Assessment of selected chlorinated and brominated flame retardants in human plasma samples among co-residing family members.

Three hexachloronorbornene-based flame retardants and five polybrominated diphenyl ethers (PBDEs) were measured in 414 human plasma samples, (169 from children, 167 from mothers, and 78 from fathers), collected from 200 families between 2014 and 2016. The median concentration of ∑PBDEs (sum of BDE-47, -99, -100, -153 and -183) was 13.2 ng/g lipid for child, 9.03 ng/g lipid for mother and 12.7 ng/g lipid for father, respectively. Among the hexachloronorbornene-based flame retardants, Dec 602 was the most frequently detected chemical. Significant and positive correlations between the concentrations of PBDE congeners as well as between Dec 602 and Dec 603 were observed. Concentrations of PBDE congeners also showed significant and positive correlations in paired samples from family members (child-mother-father), while Dec 602 was the only hexachloronorbornene-based flame retardant whose concentrations correlated between family members, and only in mother-father paired samples. This is the largest study to date focusing on measuring and correlating HRFs in children and their parents living in the same household. The results convey important information on human exposure to measured HFRs, which can help researchers and regulators more clearly understand the influence of diet and the home environment.

miRNA Profiles in Extracellular Vesicles From Serum Early in Pregnancies Complicated by Gestational Diabetes Mellitus.

CONTEXT: Underlying mechanisms leading to gestational diabetes mellitus (GDM) are still under investigation, and it is unclear whether the placenta plays a role in triggering glucose intolerance or if its functions are modified in response to the hyperglycemia. Circulating miRNAs are involved in placental development and function and are encapsulated in extracellular vesicles (EVs). OBJECTIVE: To compare differential expression of miRNAs in circulating EVs in pregnancies complicated by GDM vs controls. METHODS: This was a case-control study nested in a prospective pregnancy cohort including 23 women with GDM and 46 matched controls. The presence of serum EVs in early pregnancy was validated by transmission electron microscopy. Placental dimensions were assessed at 11 to 13 weeks of gestation. Differential expression of 17 miRNAs encapsulated in EVs (miR‒122-5p, miR‒132-3p, miR-1323, miR‒182-3p, miR‒210-3p, miR‒29a-3p, miR‒29b-3p, miR‒342-3p, miR‒517-5p, miR‒517a-3p, miR‒518b, miR-520h, miR‒525-5p, miR‒136-5p, miR‒342-3p, miR‒376c-5p, and miR‒494-3p) was assessed using quantitative reverse transcription PCR. RESULTS: EVs were present in the early phase of placentation (6 to 15 weeks of gestation) in both cases and controls. No differences were observed for placental dimensions and estimated placental volume between GDM and control groups. Ten miRNAs (miR‒122-5p; miR‒132-3p; miR‒1323; miR‒136-5p; miR‒182-3p; miR‒210-3p; miR‒29a-3p; miR‒29b-3p; miR‒342-3p, and miR-520h) showed significantly higher levels in GDM cases than in controls (P ≤ 0.05). Bioinformatics analysis showed that these miRNAs are involved in trophoblast proliferation/differentiation as well as in insulin secretion/regulation and glucose transport in pregnant women. CONCLUSION: The miRNA content of blood EVs may be a promising avenue for studying the early effect of impaired glucose metabolism on placental development.

Associations of prenatal exposure to polybrominated diphenyl ethers and polychlorinated biphenyls with long-term gut microbiome structure: a pilot study.

BACKGROUND: The gut microbiome is influenced by early-life exposures, but-despite potentially enormous implications for child health-is understudied in environmental epidemiology. This pilot study is one of the first to explore in utero exposures and long-term gut microbiome profiles. We examined the association between exposure to polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) during pregnancy and the mid-childhood gut microbiome. METHODS: We measured levels of PBDE-47, -99, -100, and -153 and PCB-138, -153, and -180 in maternal plasma during early pregnancy (n=18) and at delivery (n=25) in women of European descent who breastfed the child participant of the Gestation and Environment cohort in Sherbrooke, Québec (recruited 2007-2009). Bacteria in the mid-childhood (6-8 years) fecal microbiome were detected with 16S rRNA sequencing. To test for differences at the taxon level, we used the Microbiome Comprehensive Association Mapping algorithm. RESULTS: Early pregnancy PCB-153, -180, and the sum of PCBs (Σ3PCB) concentrations were associated with a higher relative abundance of Propionibacteriales and Propionibacteriaceae in mid-childhood. Higher PCB-180 and Σ3PCB were associated with higher relative abundance of Bacillales Family XI. Higher PBDE-99 exposure was associated with a decrease in uncultured bacteria within the Ruminococcaceae NK4A214 group and PBDE-47 was associated with differences in Ruminococcus 2. These taxon-level changes did not result in differences in within- or between-subject diversity. Exposures at delivery were not associated with differences in taxa. CONCLUSIONS: Prenatal exposure to PCBs and PBDEs is associated with mid-childhood gut microbiome profiles. Larger studies are needed to confirm these results and explore health implications.

Prenatal determinants of childhood obesity: a review of risk factors 1.

Childhood obesity is a predictor of adult obesity and has its roots in the pre-pregnancy or pregnancy period. This review presents an overview of the prenatal risk factors for childhood obesity, which were categorized into 2 groups: biological risk factors (maternal pre-pregnancy body mass index, gestational weight gain, diabetes in pregnancy, and caesarean section), and environmental and behavioural risk factors (maternal smoking and exposure to obesogens, maternal dietary patterns, maternal intestinal microbiome and antibiotics exposure, and maternal psychosocial stress). Identifying modifiable predisposing prenatal factors for obesity will inform further development of inventions to prevent obesity over the life course, and future directions for research and intervention are discussed.

Monitoring of prenatal exposure to organic and inorganic contaminants using meconium from an Eastern Canada cohort.

Evaluating in utero exposure to inorganic and multiclass organic contaminants is critical to better evaluate potential harmful effects on prenatal and postnatal development. The analysis of meconium, the first bowel discharge of the newborn, has been proposed as a non-invasive way to assess cumulative prenatal exposure. The aim of this study was to implement an analytical method for quantifying 72 targeted organic compounds, including pesticides, pharmaceutical compounds and daily life xenobiotics, in meconium in addition to selected elements (17 elements). We report initial monitoring results based on the analysis of 396 meconium samples from an Eastern Canada cohort (Quebec, Canada). Element contents in meconium were analysed by mass spectrometry after digestion in nitric acid and peroxide. Targeted organic compounds were extracted and purified from meconium samples by a solid-liquid extraction followed by a dispersive-SPE purification before tandem mass spectrometry analysis. Concentrations of targeted elements were within the range of concentration reported in European and US studies but were lower than concentrations found in a developing country cohort (i.e., Pb, Cd). Out of the 72 targeted organic compounds, 31 were detected at least once and 30 were quantified. Compounds with the highest frequency of detection were caffeine, detected in all samples (from 2.80 to 6186 ng g-1), followed by acetaminophen detected in 53% of the samples (up to ~402 µg g-1) and methyl paraben detected in 20% of the samples (up to ~10 µg g-1). Pesticides were detected in low frequencies (< 2%) and low concentration (< 35 ng g-1). Results show that meconium can be used to monitor prenatal exposure of foetus to a wide array of inorganic and organic contaminants.

Association Between Meconium Acetaminophen and Childhood Neurocognitive Development in GESTE, a Canadian Cohort Study.

Acetaminophen is the only over-the-counter pain reliever that is not contraindicated during pregnancy, but recent studies have questioned whether acetaminophen is safe for the fetus, particularly the developing brain. This prospective birth cohort study probed the previously observed association between in utero exposure to acetaminophen and neurodevelopment by using concentrations of acetaminophen measured in meconium, which more objectively captures exposure of the fetus than maternal report. Exposure, measured by liquid chromatography coupled with tandem mass spectrometry, was categorized into nondetection, low detection, and high detection levels. At age 6-8 years, children completed a set of subtests from the Wechsler Intelligence Scale for Children, 4th edition. Additionally, this study examined potential effect modification by child sex on the association between acetaminophen exposure and neurodevelopment. In fully adjusted models, in utero exposure to acetaminophen was not statistically significantly associated with decreased scores on any of the examined subtests in all children combined (n = 118). The effect of in utero acetaminophen exposure on the Coding subtest was marginally significantly different among boys and girls, with girls performing significantly better on the task with higher levels of acetaminophen compared with girls with undetectable levels of exposure (ßgirls, low = 2.83 [0.97, 4.70], ßgirls, high = 1.95 [-0.03, 3.93], ßboys, low = .02 [-1.78, 1.81], ßboys, high = -.39 [-2.09, 1.31], pinteraction = .06). Effect modification by child sex was not observed on other subtests. These results do not support prior reports of adverse neurodevelopmental effects of in utero exposure to acetaminophen.

Advanced Neonatal Medicine in China: A National Baseline Database.

Previous surveys of neonatal medicine in China have not collected comprehensive information on workforce, investment, health care practice, and disease expenditure. The goal of the present study was to develop a national database of neonatal care units and compare present outcomes data in conjunction with health care practices and costs. We summarized the above components by extracting data from the databases of the national key clinical subspecialty proposals issued by national health authority in China, as well as publicly accessible databases. Sixty-one newborn clinical units from provincial or ministerial hospitals at the highest level within local areas in mainland China, were included for the study. Data were gathered for three consecutive years (2008-2010) in 28 of 31 provincial districts in mainland China. Of the 61 newborn units in 2010, there were 4,948 beds (median = 62 [IQR 43-110]), 1,369 physicians (median = 22 [IQR 15-29]), 3,443 nurses (median = 52 [IQR 33-81]), and 170,159 inpatient discharges (median = 2,612 [IQR 1,436-3,804]). During 2008-2010, the median yearly investment for a single newborn unit was US$344,700 (IQR 166,100-585,800), median length of hospital stay for overall inpatient newborns 9.5 (IQR 8.2-10.8) days, median inpatient antimicrobial drug use rate 68.7% (IQR 49.8-87.0), and median nosocomial infection rate 3.2% (IQR1.7-5.4). For the common newborn diseases of pneumonia, sepsis, respiratory distress syndrome, and very low birth weight (<1,500 grams) infants, their lengths of hospital stay, daily costs, hospital costs, ratios of hospital cost to per-capita disposable income, and ratios of hospital cost to per-capita health expenditure, were all significantly different across regions (North China, Northeast China, East China, South Central China, Southwest China, and Northwest China). The survival rate of extremely low birth weight (ELBW) infants (Birth weight <1,000 grams) was 76.0% during 2008-2010 in the five hospitals where each unit had more than 20 admissions of ELBW infants in 2010; and the median hospital cost for a single hospital stay in ELBW infants was US$8,613 (IQR 8,153-9,216), which was 3.0 times (IQR 2.0-3.2) the average per-capita disposable income, or 63 times (IQR 40.3-72.1) the average per-capita health expenditure of local urban residents in 2011. Our national database provides baseline data on the status of advanced neonatal medicine in China, gathering valuable information for quality improvement, decision making, longitudinal studies and horizontal comparisons.

Univariate predictors of maternal concentrations of environmental chemicals: The MIREC study.

BACKGROUND: The developing fetus and pregnant woman can be exposed to a variety of environmental chemicals that may adversely affect their health. Moreover, environmental exposure and risk disparities are associated with different social determinants, including socioeconomic status (SES) and demographic indicators. Our aim was to investigate whether and how maternal concentrations of a large panel of persistent and non-persistent environmental chemicals vary according to sociodemographic and lifestyle characteristics in a large pregnancy and birth cohort. METHODS: Data were analyzed from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a cohort of pregnant women (N=2001) recruited over four years (2008-2011) in 10 cities across Canada. In all, 1890 urine and 1938 blood samples from the first trimester (1st and 3rd trimester for metals) were analysed and six sociodemographic and lifestyle indicators were assessed: maternal age, household income, parity, smoking status, country of birth and pre-pregnancy body mass index (BMI). RESULTS: We found these indicators to be significantly associated with many of the chemicals measured in maternal blood and urine. Women born outside Canada had significantly higher concentrations of di-2-ethylhexyl and diethyl phthalate metabolites, higher levels of all metals except cadmium (Cd), as well as higher levels of polychlorinated biphenyls (PCBs) and legacy organochlorine pesticides (OCPs). Nulliparity was associated with higher concentrations of dialkyl phosphates (DAPs), arsenic, dimethylarsinic acid (DMAA), perfluoroalkyl substances (PFASs) and many of the persistent organic pollutants. Smokers had higher levels of bisphenol A, Cd and perfluorohexane sulfonate, while those women who had never smoked had higher levels of triclosan, DMAA, manganese and some OCPs. CONCLUSION: Our results demonstrated that inequitable distribution of exposure to chemicals among populations within a country can occur. Sociodemographic and lifestyle factors are an important component of a thorough risk assessment as they can impact the degree of exposure and may modify the individual's susceptibility to potential health effects due to differences in lifestyle, cultural diets, and aging.

Maternal levels of endocrine disruptors, polybrominated diphenyl ethers, in early pregnancy are not associated with lower birth weight in the Canadian birth cohort GESTE.

BACKGROUND: Polybrominated diphenyl ethers are known endocrine disrupting environmental contaminants used as flame retardants. Their levels have increased in humans over the last ten years, raising concerns about their consequences on human health. Some animal studies suggest that PBDEs can affect fetal growth; however, the results of human studies are contradictory. This study evaluates the association between the most common PBDEs in maternal blood measured in early pregnancy and birth weight. METHODS: BDE-47, BDE-99, BDE-100 and BDE-153 levels were measured in 349 women during their first prenatal care visit at the University Hospital Center of Sherbrooke (Quebec, Canada). Birth weight and relevant medical information were collected from medical records. In contrast with previous studies, we examined the full range of clinical risk factors known to affect fetal growth as potential confounders, as well as other environmental pollutants that are likely to interact with fetal growth (polychlorinated biphenyls (PCBs), mercury, lead, cadmium and manganese). RESULTS: There was no statistically significant relationship between PBDE levels in early pregnancy and birth weight in both unadjusted and multivariate regression models. CONCLUSIONS: Our results suggest that PBDEs in early pregnancy have little or no direct impact on birth weight, at least at the levels of exposure in our population.

Endocrine disruption in human placenta: expression of the dioxin-inducible enzyme, CYP1A1, is correlated with that of thyroid hormone-regulated genes.

CONTEXT: Thyroid hormone (TH) is essential for normal development; therefore, disruption of TH action by a number of industrial chemicals is critical to identify. Several chemicals including polychlorinated biphenyls are metabolized by the dioxin-inducible enzyme CYP1A1; some of their metabolites can interact with the TH receptor. In animals, this mechanism is reflected by a strong correlation between the expression of CYP1A1 mRNA and TH-regulated mRNAs. If this mechanism occurs in humans, we expect that CYP1A1 expression will be positively correlated with the expression of genes regulated by TH. OBJECTIVE: The objective of the study was to test the hypothesis that CYP1A1 mRNA expression is correlated with TH-regulated mRNAs in human placenta. METHODS: One hundred sixty-four placental samples from pregnancies with no thyroid disease were obtained from the GESTE study (Sherbrooke, Québec, Canada). Maternal and cord blood TH levels were measured at birth. The mRNA levels of CYP1A1 and placental TH receptor targets [placental lactogen (PL) and GH-V] were quantitated by quantitative PCR. RESULTS: CYP1A1 mRNA abundance varied 5-fold across 132 placental samples that had detectable CYP1A1 mRNA. CYP1A1 mRNA was positively correlated with PL (r = 0.64; P < .0001) and GH-V (P < .0001, r = 0.62) mRNA. PL and GH-V mRNA were correlated with each other (r = 0.95; P < .0001), suggesting a common activator. The mRNAs not regulated by TH were not correlated with CYP1A1 expression. CONCLUSIONS: CYP1A1 mRNA expression is strongly associated with the expression of TH-regulated target gene mRNAs in human placenta, consistent with the endocrine-disrupting action of metabolites produced by CYP1A1.

Measurements of selected brominated flame retardants in nursing women: implications for human exposure.

We have examined several emerging brominated flame retardants (BFRs) including 2-ethyl-1-hexyl-2,3,4,5-tetrabromobenzoate (TBB), bis(2-ethylhexyl) tetrabromophthalate (TBPH), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), 4,5,6,7-tetrabromo-1,1,3-trimethyl-3-(2,3,4,5-tetrabromophenyl)-indane (OBIND), and decabromodiphenyl ethane (DBDPE) in paired human maternal serum (n = 102) and breast milk (n = 105) collected in 2008-2009 in the Sherbrooke region in Canada. Three legacy BFRs were also included in the study for comparison: decabromobiphenyl (BB-209), 2,2',4,4',5,5'-hexabromobiphenyl (BB-153), and 2,2',4,4',5,5'-hexabromodiphenyl ethers (BDE-153). TBB, BB-153, and BDE-153 had detection frequencies greater than 55% in both serum and milk samples. Their lipid weight (lw) adjusted median concentrations (ng g(-1) lw) in serum and milk were 1.6 and 0.41 for TBB, 0.48 and 0.31 for BB-153, and 1.5 and 4.4 for BDE-153, respectively. The detection frequencies for the other BFRs measured in serum and milk were 16.7% and 32.4% for TBPH, 3.9% and 0.0% for BTBPE, 2.0% and 0.0% for BB-209, 9.8% and 1.0% for OBIND, and 5.9% and 8.6% for DBDPE. The ratio of TBB over the sum of TBB and TBPH (fTBB) in serum (0.23) was lower than that in milk (0.46), indicating TBB has a larger tendency than TBPH to be redistributed from blood to milk. Overall, these data confirm the presence of non-PBDE BFRs in humans, and the need to better understand their sources, routes of exposure, and potential human health effects.

Hexachloronorbornene-based flame retardants in humans: levels in maternal serum and milk.

Five hexachloronorbornene-based flame retardants, Dechlorane Plus (DP), Dechlorane 602 (Dec 602), Dechlorane 603 (Dec 603), Dechlorane 604 (Dec 604) and hexachlorocyclopentadienyl-dibromocyclooctane (HCDBCO), were measured in human milk and maternal serum. Dec 602, Dec 603 and HCDBCO were detected in both sample matrices with detection frequencies over 60%. Dec 604 was not detected in serum and only detected in 4.8% of milk samples. DP was present in over 77-87% of serum and 40-50% of milk samples. DP levels found in this study were lower than those reported in two Chinese studies. The ratio of the two DP isomers found in human samples (f(anti-DP) = 0.8) remained similar to the ratio reported in the DP technical mixture. Levels of Dec 602 and Dec 603 in serum were correlated. Levels of Dec 602 and HCBDCO were also correlated in serum samples as well as in milk samples. These biomonitoring results have provided baseline information about the presence of these flame retardants in nursing women in Canada, which can be used for estimating human exposure to these chemicals.

Closure of the uterine incision with one or two layers after caesarean section: a randomized controlled study in sheep.

OBJECTIVE: To compare the quality of the uterine scar with one or two layer closure after caesarean section by studying biomechanical and pathological properties of the scar. METHODS: A randomized controlled trial performed on eight term pregnant ewes assigned into two groups during caesarean according to type of uterine closure: single-layer or double-layer. Hysterectomy was performed 8 months after caesarean delivery. Tensile strength of all scars and of unscarred myometrium was measured. Pathological properties of the scars were analyzed histologically. RESULTS: The force required to reach the yield point was similar between scarred and unscarred myometrium (p=0.96), and between the scars in single-layer and double-layer closure groups (p=0.65). There was a significant increase in fibrosis width on the superficial part of the uterus in the double-layer closure group compared to the single-layer group (p=0.02). CONCLUSIONS: Double-layer uterine closure modified wound healing without significant change in biomechanical properties.