EDC mixtures during pregnancy and body fat at 7 years of age in a Swedish cohort, the SELMA study.

BACKGROUND: Some endocrine disrupting chemicals (EDC), are "obesogens" and have been associated with overweight and obesity in children. Daily exposure to different classes of EDCs demands for research with mixtures approach. OBJECTIVES: This study evaluates the association, considering sex-specific effects, between prenatal exposure to EDC mixture and children's body fat at seven years of age. METHODS: A total of 26 EDCs were assessed in prenatal urine and serum samples from first trimester in pregnancy from 737 mother-child pairs participating in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. An indicator for children's "overall body fat" was calculated, using principal component analysis (PCA), based on BMI, percent body fat, waist, and skinfolds measured at seven years of age. Weighted quantile sum (WQS) regression was used to assess associations between EDC mixture and children's body fat. RESULTS: Principal component (PC1) represented 83.6 % of the variance, suitable as indicator for children's "overall body fat", with positive loadings of 0.40-0.42 for each body fat measure. A significant interaction term, WQS*sex, confirmed associations in the opposite direction for boys and girls. Higher prenatal exposure to EDC mixture was borderline significant with more "overall body fat" for boys (Mean ß = 0.20; 95 % CI: -0.13, 0.53) and less for girls (Mean ß = -0.23; 95 % CI: -0.58, 0.13). Also, higher prenatal exposure to EDC mixture was borderline significant with more percent body fat (standardized score) for boys (Mean ß = 0.09; 95 % CI: -0.04, 0.21) and less for girls (Mean ß = -0.10 (-0.26, 0.05). The chemicals of concern included bisphenols, phthalates, PFAS, PAH, and pesticides with different patterns for boys and girls. DISCUSSION: Borderline significant associations were found between prenatal exposure to a mixture of EDCs and children's body fat. The associations in opposite directions suggests that prenatal exposure to EDCs may present sex-specific effects on children's body fat.

Maternal nutrition during mid-pregnancy and children's body composition at 7 years of age in the SELMA study.

Optimal nutrition during pregnancy is vital for both maternal and child health. Our objective was to explore if prenatal diet is associated with children's height and body fat. Nutrient intake was assessed through a FFQ from 808 pregnant women and summarised to a nutrition index, 'My Nutrition Index' (MNI). The association with children's height and body fat (bioimpedance) was assessed with linear regression models. Secondary analysis was performed with BMI, trunk fat and skinfolds. Overall, higher MNI score was associated with greater height (ß = 0·47; (95 % CI 0·00, 0·94), among both sexes. Among boys, higher MNI was associated with 0·15 higher BMI z-scores, 0·12 body fat z-scores, 0·11 trunk fat z-scores, and larger triceps, and triceps + subscapular skinfolds (ß = 0·05 and ß = 0·06; on the log2 scale) (P-value < 0·05). Among girls, the opposite associations were found with 0·12 lower trunk fat z-scores, and smaller subscapular and suprailiac skinfolds (ß = -0·07 and ß = -0·10; on the log2 scale) (P-value < 0·05). For skinfold measures, this would represent a ± 1·0 millimetres difference. Unexpectedly, a prenatal diet in line with recommended nutrient intake was associated with higher measures of body fat for boys and opposite to girls at a pre-pubertal stage of development.

Association Between Intellectual Functioning and Autistic Traits in the General Population of Children.

Autistic traits are continuously distributed in the general population. The associations between autistic traits and intellectual functioning and/or behavioural difficulties, and the impact of intellectual functioning on behavioural difficulties are unclear. The study aims to describe the distribution of autistic traits in a population-based cross-sectional sample of children. Further aims are to examine the association between intellectual functioning and autistic traits, and between autistic traits and behavioural difficulties. Wechsler scales and ratings of autistic traits and behavioural problems in 874 children aged 7-9 years in the Swedish Environmental Longitudinal Mother and Child, Asthma and Allergy (SELMA) study were assessed. We found a continuous distribution of autistic traits. Intellectual functioning was negatively associated with autistic traits but not with behavioural difficulties. Behavioural difficulties were associated with autistic traits.

Phthalate levels in prenatal and postnatal bedroom dust in the SELMA study.

Phthalates are common in polyvinyl chloride (PVC) plastics and numerous consumer goods in our homes from which they can migrate and adhere to indoor dust particles. It is known that indoor dust exposure contribute to human phthalate intake; however, there is a lack of large studies with a repeated-measure design investigating how phthalate levels in indoor dust may vary over time in people's homes. This study investigated levels of seven phthalates and one alternative plasticiser di-iso-nonyl-cyclohexane-di-carboxylate (DiNCH) in bedroom dust collected prenatally around week 25 during pregnancy and postnatally at six months after birth, from 496 Swedish homes. Prenatal and postnatal phthalate levels were compared using correlation and season-adjusted general linear regression models. Over the nine-month period, levels of six out of seven phthalates were associated as indicated by a positive Pearson correlation (0.18 < r < 0.50, P < .001) and Lin's concordance correlation between matched prenatal and postnatal dust samples. Compared to prenatal levels, the season-adjusted postnatal levels decreased for five phthalates, whilst di-ethyl-hexyl phthalate (DEHP), di-2-propylheptyl phthalate (DPHP) and DiNCH increased. The results suggest that families with higher phthalate levels in bedroom dust during pregnancy are likely to remain among those with higher levels in the infancy period. However, all average phthalate levels changed over this specific nine-month period suggesting that available phthalate sources or their use were altered between the dust collections. Changes in home characteristics, family lifestyle, and phthalate replacement trends may contribute to explain the differences.

Anthropometric measures do not explain the 2D:4D ratio sexual dimorphism in 7-year-old children.

OBJECTIVES: Digit ratio (2D:4D) might reflect prenatal testosterone exposure and has been used as a putative marker for androgen related outcomes. However, such associations might be inflicted by confounders. Application of 2D:4D in epidemiological research motivate identification of biological background determinants. We examined sex, anthropometric measures, and maternal factors as determinants of 2D:4D in Swedish 7-year-old children. METHODS: The study was embedded in the Swedish Environmental, Longitudinal, Mother and Child, Asthma and Allergy (SELMA) pregnancy cohort. A total of 870 pre-pubertal children, median 7.5 years of age, were studied. A single assessor performed digit measurements from scanned photocopies using computer software. Child anthropometric measurements investigated were hand size, birthweight, recumbent birth length, standing height, weight, BMI, body fat percentage, and waist/hip circumference. Maternal factors included age, pregnancy length, parity, and education. RESULTS: We found a significant sexual dimorphism regarding digit lengths and 2D:4D, boys on average presenting a lower 2D:4D than girls also after adjustment for summed finger lengths and body fatness. In crude analyses, maternal age correlated with 2D:4D across the whole population and in females but not in adjusted models. No other study variables were associated with 2D:4D. CONCLUSION: Digit ratio showed sexual dimorphism at the age of seven and seems to represent a true sex difference rather than an artifact and bias from hand size, body size or body fat content. Among the rest of our investigated variables, we found no determinants constituting important confounders in future research on 2D:4D ratio.

A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells.

Endocrine Disrupting Chemicals (EDCs) are man-made compounds that alter functions of the endocrine system. Environmental mixtures of EDCs might have adverse effects on human health, even though their individual concentrations are below regulatory levels of concerns. However, studies identifying and experimentally testing adverse effects of real-life mixtures are scarce. In this study, we aimed at evaluating an epidemiologically identified EDC mixture in an experimental setting to delineate its cellular and epigenetic effects. The mixture was established using data from the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study where it was associated with lower birth weight, an early marker for prenatal metabolic programming. This mixture was then tested for its ability to change metabolic programming of human mesenchymal stem cells. In these cells, we assessed if the mixture induced adipogenesis and genome-wide DNA methylation changes. The mixture increased lipid droplet accumulation already at concentrations corresponding to levels measured in the pregnant women of the SELMA study. Furthermore, we identified differentially methylated regions in genes important for adipogenesis and thermogenesis. This study shows that a mixture reflecting human real-life exposure can induce molecular and cellular changes during development that could underlie adverse outcomes.

Indoor phthalate exposure and contributions to total intake among pregnant women in the SELMA study.

Phthalates are widely used in consumer products. Exposure to phthalates can lead to adverse health effects in humans, with early-life exposure being of particular concern. Phthalate exposure occurs mainly through ingestion, inhalation, and dermal absorption. However, our understanding of the relative importance of different exposure routes is incomplete. This study estimated the intake of five phthalates from the residential indoor environment for 455 Swedish pregnant women in the SELMA study using phthalate mass fraction in indoor dust and compares these to total daily phthalate intakes back-calculated from phthalate metabolite concentrations in the women's urine. Steady-state models were used to estimate indoor air phthalate concentrations from dust measurements. Intakes from residential dust and air made meaningful contributions to total daily intakes of more volatile di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), and di-iso-butyl phthalate (DiBP) (11% of total DEP intake and 28% of total DnBP and DiBP intake combined). Dermal absorption from air was the dominant pathway contributing to the indoor environmental exposure. Residential exposure to less volatile phthalates made minor contributions to total intake. These results suggest that reducing the presence of low molecular weight phthalates in the residential indoor environment can meaningfully reduce phthalate intake among pregnant women.

Number of words at age 2.5 years is associated with intellectual functioning at age 7 years in the SELMA study.

AIM: We examined the association between the number of words used at age 2.5 years and deficits in intellectual functioning at age 7 years, in 549 children, and whether such association is confirmed by parental concern about the child's development. METHODS: Parental reports of how many words their children used at age 2.5 years were analysed for the association to intellectual functioning (assessed with Wechsler Intelligence Scale for Children - Fourth Edition,WISC-IV) at age 7 years using linear regression, adjusting for sex, maternal education level, parental IQ and smoking during pregnancy. Parental concern at age 7 years was examined with the Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations-Questionnaire (ESSENCE-Q). RESULTS: Adjusted linear regression showed that use of 50 words or fewer at age 2.5 years, relative to use of more than 50 words, was associated with lower scores of Full-scale IQ (B = 7.27, p = 0.001), verbal comprehension (B = 8.53, p < 0.001), working memory (B = 9.04, p < 0.001) and perceptual reasoning (B = 4.21, p = 0.045), in the WISC-IV, at age 7 years. Parental concern was more common in the group that used 50 words or fewer (Mann-Whitney U test, p = 0.011). CONCLUSION: This easily accessible measure of number of words seems to be a valuable marker for intellectual functioning later in life.

Maternal serum levels of perfluoroalkyl substances in early pregnancy and offspring birth weight.

BACKGROUND: Perfluoroalkyl substances (PFASs) are widespread, bioaccumulating, and persistent and show placental transfer. Emerging research indicates associations between prenatal exposure and low birth weight. The aim of this study was to assess the associations between first trimester exposure to PFASs and birth weight (BW) in the Swedish Environmental, Longitudinal, Mother and child, Asthma and allergy (SELMA) study and examine whether associations differ between girls and boys. METHODS: Eight PFASs were analyzed in maternal serum (median: 10 weeks of pregnancy). Associations between prenatal PFAS exposure and birth outcomes with BW, BW for gestational age, and birth small for gestational age (SGA) were assessed in 1533 infants, adjusted for potential confounders and stratified by sex. RESULTS: Increased maternal perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were associated with lower BW, lower BW for gestational age, and SGA birth. Associations were significant only in girls, where prenatal exposure in the upper quartile was associated with a 93-142-g lower BW when compared with that of the lowest quartile exposure. The associations were not mediated by effects on gestational age. CONCLUSIONS: We found associations between prenatal exposure for five different PFASs and birth weight, with more pronounced associations in girls than in boys.

Dynamic growth metrics for examining prenatal exposure impacts on child growth trajectories: Application to perfluorooctanoic acid (PFOA) and postnatal weight gain.

BACKGROUND: Epidemiologic studies investigating prenatal exposures in relation to growth typically rely on cumulative growth measures such as weight or BMI. However, less is known about how prenatal exposure may impact other aspects of growth dynamics, including timing and velocity. OBJECTIVES: To describe and apply a nonlinear growth model previously used in other health science fields to characterize postnatal growth trajectories for use in environmental epidemiology studies. METHODS: We used a double logistic function to model child weight trajectories from birth to 5.5 years using data from the Swedish Environmental Longitudinal Mother and Child, Asthma and Allergy (SELMA) study. From this, we approximated several infant growth metrics: 1) duration of time needed to complete 90% of the infant growth spurt (Δt1), 2) the maximum growth rate in infancy or infant peak growth velocity (PGV), 3) the age at infant PGV (δ1), a measure of growth tempo, and 4) the weight plateau at the end of the infant growth spurt (α1). We assessed these metrics in relation to prenatal perfluorooctanoic acid (PFOA) exposure among 1334 mother-child pairs, and differences between boys and girls. RESULTS: Average estimated infant PGV and its timing (δ1) were 0.68 kg/month and 3.4 months, respectively. Mean infant growth spurt duration (Δt1) was 13 months, ending at an average weight plateau (α1) of 8.2 kg. Higher prenatal PFOA concentrations were related to a longer duration of infant growth (Δt1: 0.06; 95% CI = 0.01, 0.11). PGV was not impacted, but higher prenatal PFOA concentrations were significantly related to delayed infant PGV (δ1: 0.58; 95% CI = 0.17, 0.99) and a higher post-spurt weight plateau (α1: 0.81; 95% CI = 0.21, 1.41). After adjusting for false discovery, results were only significant for δ1 and α1. We observed a significant interaction by sex for the association with δ1, and stratified analyses revealed the association was only significant among girls. CONCLUSION: Model-derived growth metrics were consistent with published growth standards. This novel application of nonlinear growth modeling enabled detection of altered infant growth dynamics in relation to prenatal PFOA exposure. Our results may help describe how PFOA yields lower birthweights, but higher weight later in childhood. Future applications may characterize adolescent growth or additional metrics of biological interest.

Persistent organic pollutants, pre-pregnancy use of combined oral contraceptives, age, and time-to-pregnancy in the SELMA cohort.

BACKGROUND: We are exposed to several chemicals such as persistent organic pollutants (POPs) in our everyday lives. Prior evidence has suggested that POPs may have adverse effects on reproductive function by disrupting hormone synthesis and metabolism. While there is age-related decline of fertility, the use of hormonal combined oral contraceptives (COCs) and its association to return of fertility remains controversial. The goal of this study is to investigate the association between exposure to POPs, both individually and as a mixture, and fecundability measured as time-to-pregnancy (TTP) according to pre-pregnancy use of COCs and age. METHODS: Using the SELMA (Swedish Environmental Longitudinal Mother and Child, Allergy and Asthma) study, we have identified 818 pregnant women aged 18-43 years (mean 29 years) with data on how long they tried to get pregnant and what was their most recently used contraceptive method. These data were collected at enrollment to the study (median week 10 of pregnancy). Concentrations of 22 POPs and cotinine were analyzed in the blood samples collected at the same time as the questions on TTP and pre-pregnancy use of contraceptive. Analyses were done on the association between POPs exposure and TTP measured as continuous (months) and binary (infertile for those with TTP > 12 months). To study the chemicals individually, Cox regression and logistic regression were used to estimate fecundability ratios (FRs) and odds ratios (ORs), respectively. Weighted quantile sum (WQS) regression was used to investigate the chemicals as a mixture where chemicals of concern were identified above the 7.6% threshold of equal weights. To perform the subgroup analysis, we stratified the sample according to use of COCs as the most recent pre-pregnancy contraception method and age (< 29 years, and ≥ 29 years). The models were adjusted for parity, regularity of menses, maternal body mass index (BMI) and smoking status, and stratified as described above. RESULTS: Prior to stratification, none of the POPs were associated with fecundability while increased exposure to HCB, PCB 74 and 118 had higher odds of infertility. Upon stratification, POP exposure was significantly associated with longer TTP in women aged ≥29 years who did not use COC. Specifically, PCBs 156, 180, 183, and 187 were associated with reduced fecundability while PCBs 99, 153, 156, 180, 183, and 187 had higher odds of infertility. As a mixture, we identified the chemicals of concern for a longer TTP include PCBs 118, 156, 183, and 187. Moreover, chemicals of concern identified with increased odds of infertility were PCB 74, 156, 183, 187, and transnonachlor. CONCLUSION: Serum concentrations of selected POPs, both as individual chemicals and as a mixture, were significantly associated with lower fecundability and increased odds of infertility in women aged 29 years and above not using COC as their most recent pre-pregnancy contraceptive. Our findings suggest that pre-pregnancy use of oral contraceptive and age may modify the link between POPs and fecundability. The differences of specific chemicals in the individual analysis and as a mixture support the need to study combination effects of chemicals when evaluating reproductive outcomes.

A suggested bisphenol A metabolite (MBP) interfered with reproductive organ development in the chicken embryo while a human-relevant mixture of phthalate monoesters had no such effects.

Bisphenol A (BPA) and phthalate diesters are ubiquitous environmental contaminants. While these compounds have been reported as reproductive toxicants, their effects may partially be attributed to metabolites. The aim of this study was to examine reproductive organ development in chicken embryos exposed to the BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP; 100 µg/g egg) or a human-relevant mixture of 4 phthalate monoesters (85 µg/g egg). The mixture was designed within the EU project EDC-MixRisk based upon a negative association with anogenital distance in boys at 21 months of age in a Swedish pregnancy cohort. Chicken embryos were exposed in ovo from an initial stage of gonad differentiation (embryonic day 4) and dissected two days prior to anticipated hatching (embryonic day 19). No discernible effects were noted on reproductive organs in embryos exposed to the mixture. MBP-treated males exhibited retention of Müllerian ducts and feminization of the left testicle, while MBP-administered females displayed a diminished the left ovary. In the left testicle of MBP-treated males, mRNA expression of female-associated genes was upregulated while the testicular marker gene SOX9 was downregulated, corroborating a feminizing effect by MBP. Our results demonstrate that MBP, but not the phthalate monoester mixture, disrupts both male and female reproductive organ development in an avian embryo model.

The ENDpoiNTs Project: Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity.

Ubiquitous exposure to endocrine-disrupting chemicals (EDCs) has caused serious concerns about the ability of these chemicals to affect neurodevelopment, among others. Since endocrine disruption (ED)-induced developmental neurotoxicity (DNT) is hardly covered by the chemical testing tools that are currently in regulatory use, the Horizon 2020 research and innovation action ENDpoiNTs has been launched to fill the scientific and methodological gaps related to the assessment of this type of chemical toxicity. The ENDpoiNTs project will generate new knowledge about ED-induced DNT and aims to develop and improve in vitro, in vivo, and in silico models pertaining to ED-linked DNT outcomes for chemical testing. This will be achieved by establishing correlative and causal links between known and novel neurodevelopmental endpoints and endocrine pathways through integration of molecular, cellular, and organismal data from in vitro and in vivo models. Based on this knowledge, the project aims to provide adverse outcome pathways (AOPs) for ED-induced DNT and to develop and integrate new testing tools with high relevance for human health into European and international regulatory frameworks.

Removing Critical Gaps in Chemical Test Methods by Developing New Assays for the Identification of Thyroid Hormone System-Disrupting Chemicals-The ATHENA Project.

The test methods that currently exist for the identification of thyroid hormone system-disrupting chemicals are woefully inadequate. There are currently no internationally validated in vitro assays, and test methods that can capture the consequences of diminished or enhanced thyroid hormone action on the developing brain are missing entirely. These gaps put the public at risk and risk assessors in a difficult position. Decisions about the status of chemicals as thyroid hormone system disruptors currently are based on inadequate toxicity data. The ATHENA project (Assays for the identification of Thyroid Hormone axis-disrupting chemicals: Elaborating Novel Assessment strategies) has been conceived to address these gaps. The project will develop new test methods for the disruption of thyroid hormone transport across biological barriers such as the blood-brain and blood-placenta barriers. It will also devise methods for the disruption of the downstream effects on the brain. ATHENA will deliver a testing strategy based on those elements of the thyroid hormone system that, when disrupted, could have the greatest impact on diminished or enhanced thyroid hormone action and therefore should be targeted through effective testing. To further enhance the impact of the ATHENA test method developments, the project will develop concepts for better international collaboration and development in the area of thyroid hormone system disruptor identification and regulation.

PVC flooring at home and uptake of phthalates in pregnant women.

Phthalates are used as plasticizers in polyvinyl chloride (PVC) materials and it is known that phthalates may migrate into the surrounding environment and then become a source for human uptake. The aim of the study was to investigate whether residential PVC flooring was related to the urinary levels of phthalate metabolites determined in pregnant women. The data were from the Swedish SELMA study where sampling was conducted during the time period 2007-2010. Spot urine samples from 1674 women at the end of the first trimester were analyzed for 14 metabolites from seven phthalates and one phthalate alternative. Data on flooring material in the kitchen and the parents' bedrooms as well as potential confounders were collected by postal questionnaires at the same time as the urine samples were taken. Multiple regression modeling by least square geometric mean and weighted quantile sum regression was applied to log-transformed and creatinine-adjusted phthalate metabolite concentrations adjusted for potential confounders from questionnaire data. This study has found significantly higher urinary levels of the BBzP metabolite (MBzP) in pregnant women living in homes with PVC flooring as compared to homes with other flooring materials.

A Novel Approach to Chemical Mixture Risk Assessment-Linking Data from Population-Based Epidemiology and Experimental Animal Tests.

Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs ("bad actors")-measured in prenatal blood/urine in the SELMA study-that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a "typical" mixture consisting of the "bad actors" identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose-response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of "sufficient similarity" to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a "similar mixture risk indicator" (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound-by-compound strategy (1.6%).

Prenatal paracetamol exposure and child neurodevelopment: A review.

BACKGROUND: The non-prescription medication paracetamol (acetaminophen, APAP) is currently recommended as a safe pain and fever treatment during pregnancy. However, recent studies suggest a possible association between APAP use in pregnancy and offspring neurodevelopment. OBJECTIVES: To conduct a review of publications reporting associations between prenatal APAP use and offspring neurodevelopmental outcomes. METHODS: Relevant sources were identified through a key word search of multiple databases (Medline, CINAHL, OVID and TOXNET) in September 2016. All English language observational studies of pregnancy APAP and three classes of neurodevelopmental outcomes (autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intelligence quotient (IQ)) were included. One reviewer (AZB) independently screened all titles and abstracts, extracted and analyzed the data. RESULTS: 64 studies were retrieved and 55 were ineligible. Nine prospective cohort studies fulfilled all inclusion criteria. Data pooling was not appropriate due to heterogeneity in outcomes. All included studies suggested an association between prenatal APAP exposure and the neurodevelopmental outcomes; ADHD, ASD, or lower IQ. Longer duration of APAP use was associated with increased risk. Associations were strongest for hyperactivity and attention-related outcomes. Little modification of associations by indication for use was reported. CONCLUSIONS: Together, these nine studies suggest an increased risk of adverse neurodevelopmental outcomes following prenatal APAP exposure. Further studies are urgently needed with; precise indication of use and exposure assessment of use both in utero and in early life. Given the current findings, pregnant women should be cautioned against indiscriminate use of APAP. These results have substantial public health implications.

Prenatal phthalate exposure was associated with croup in Swedish infants.

AIM: This study examined whether prenatal phthalate exposure was associated with lower or upper airway inflammation in infants. METHODS: From 2007 to 2010, we used liquid chromatography-tandem mass spectrometry, adjusted for creatinine, to analyse 14 phthalate metabolites and one phthalate replacement in the urine of 1062 Swedish mothers at a median of 10 weeks of pregnancy. This was used to determine any associations between prenatal phthalate exposure and croup, wheezing or otitis in their offspring until 12 months of age, using logistic regression, adjusted for potential confounders. RESULTS: There were significant associations between phthalate metabolites of butyl-benzyl phthalate (BBzP) and di-ethyl-hexyl phthalate (DEHP) concentrations in maternal prenatal urine and croup in 1062 infants during the first year of life, when adjusted for potential confounders. A dose-response relationship was found between prenatal phthalates exposure and maternal reported croup in the children, with a significant association in boys. There was no clear indication with regard to associations between prenatal phthalate exposure and wheezing or otitis media in the children during the first year of life. CONCLUSION: Our analysis suggests that exposure to BBzP and DEHP phthalates was associated with maternal reports of croup in infants up to 12 months of age.

Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour.

Paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) is the preferred analgesic for pain relief and fever during pregnancy. It has therefore caused concern that several studies have reported that prenatal exposure to APAP results in developmental alterations in both the reproductive tract and the brain. Genitals and nervous system of male mammals are actively masculinised during foetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behaviour seen in adulthood. Both androgens and prostaglandins are known to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant and precursor of APAP, aniline, resulted in a similar reduction. Decrease in neuronal number in the SDN-POA is associated with reductions in male sexual behaviour. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behaviour as adults and had a less aggressive territorial display towards intruders of the same gender. Additionally, exposed males had reduced intromissions and ejaculations during mating with females in oestrus. Together, these data suggest that prenatal exposure to APAP may impair male sexual behaviour in adulthood by disrupting the sexual neurobehavioral programming. These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP by pregnant women.

Swedish population-based study of pupils showed that foster children faced increased risks for ill health, negative lifestyles and school failure.

AIM: This population-based study explored whether foster children faced a higher risk of health problems than children of the same age who were not in foster care. METHODS: Data for 13 739 pupils aged 10, 13 and 16 years were obtained from the Pupil Health Database in the county of Värmland, Sweden, for the school years 2012/2013 and 2013/2014. These included data on school performance, health, lifestyle and social relationships, based on children's interviews with school nurses. RESULTS: Of all the pupils, 171 (1.2%) were in foster care. Children in foster care were generally unhealthier than other children. Both girls and boys were at higher risk of chronic health problems, daily smoking, use of drugs and school failure. When the girls in foster care were compared to other girls, we found that they faced a higher risk of psychological and psychosomatic symptoms. This difference was not found for boys. Foster children were also more likely to express a more negative view on life. CONCLUSION: We confirmed earlier studies that children in foster care tended to have inferior health and well-being than other children. These findings emphasise that health, risky behaviour and school performance should be considered together when assessing foster children.