Do Wechsler intelligence scales predict academic achievement in children with ADHD or autism? A systematic review and meta-analysis.

Intelligence tests predict academic achievement in typically developed children, however if this is the case also in children with attention-deficit/hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) is not clear. This systematic review and meta-analysis examined if Wechsler intelligence scales predict academic achievement and/or grades in children, ages 6-16 years, with ADHD and/or ASD. We searched the databases PubMed, PsycINFO and Education Research Complete for studies published between 2000 and 2023. We used the Newcastle-Ottawa Scale to assess risk of bias. Narrative synthesis and meta-analysis were performed. Twelve studies (ADHD n = 1,834, ASD n = 176) were included in the review, and six samples (ADHD n = 1,112) of those were included in the meta-analyses. The results of the meta-analyses showed moderate overall weighted correlations between IQ and word reading, written language, and mathematics respectively. Similarly, the overall weighted correlations between processing speed and the aforementioned domains of academic achievement were moderate. Meta-analysis with additional Wechsler scales composite scores could not be conducted. In the narrative synthesis, Full Scale IQ was associated with academic achievement in both ADHD and ASD, and grades in ADHD. The limited number of ASD participants and the heterogeneity of the samples need to be considered when interpreting results. Generally, the results indicate that Wechsler scales are valuable in predicting academic achievement in children with ADHD or ASD. Motivation and other factors related with academic achievement need to be further explored in these groups.

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.

Prenatal exposures to mixtures of endocrine disrupting chemicals and sex-specific associations with children's BMI and overweight at 5.5 years of age in the SELMA study.

BACKGROUND: Prenatal exposure to mixtures of endocrine disrupting chemicals (EDC) has the potential to disrupt human metabolism. Prenatal periods are especially sensitive as many developmental processes are regulated by hormones. Prenatal exposure to EDCs has inconsistently been associated with children's body mass index (BMI) and obesity. The objective of this study was to investigate if prenatal exposure to a mixture of EDCs was associated with children's BMI and overweight (ISO-BMI ≥ 25) at 5.5 years of age, and if there were sex-specific effects. METHODS: A total of 1,105 mother-child pairs with complete data on prenatal EDCs concentrations (e.g., phthalates, non-phthalate plasticizers, phenols, PAH, pesticides, PFAS, organochlorine pesticides, and PCBs), children's measured height and weight, and selected covariates in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study were included in this analysis. The mixture effect of EDCs with children's BMI and overweight was assessed using WQS regression with 100 repeated holdouts. A positively associated WQS index with higher BMI and odds of overweight was derived. Models with interaction term and stratified weights by sex was applied in order to evaluate sex-specific associations. RESULTS: A significant WQS*sex interaction term was identified and associations for boys and girls were in opposite directions. Higher prenatal exposure to a mixture of EDCs was associated with lower BMI (Mean ß = -0.19, 95%CI: -0.40, 0.01) and lower odds of overweight (Mean OR = 0.72, 95%CI: 0.48, 1.04) among girls with borderline significance. However, the association among boys did not reach statistical significance. Among girls, the possible chemicals of concern were MEP, 2-OHPH, BPF, BPS, DPP and PFNA. CONCLUSION: Prenatal exposure to a mixture of EDCs was associated with lower BMI and overweight among girls, and non-significant associations among boys. Chemicals of concern for girls included phthalates, non-phthalate plasticizers, bisphenols, PAHs, and PFAS.

Association of endocrine disrupting chemicals exposure with human chorionic gonadotropin concentrations in pregnancy.

BACKGROUND: Human chorionic gonadotropin (hCG) is produced by the placenta and plays an essential role in the maintenance of pregnancy. Endocrine disrupting chemicals (EDCs) have the potential to interfere with functions related to the production and secretion of hCG; however associations between exposure to EDCs and hCG concentrations in humans remain to be elucidated. OBJECTIVES: To investigate the association of urinary, serum and plasma concentrations of EDCs during pregnancy with serum hCG concentrations. METHODS: We utilized data form the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. We investigated the association of 26 EDCs measured in early pregnancy urine or blood with serum hCG concentrations using multi-variable adjusted linear regression models per EDC and Weighted Quantile Sum (WQS) regression with repeated holdout validation for the EDCs mixture. RESULTS: In 2,039 included women, higher exposure to bisphenol A was associated with lower hCG (beta [95% CI]: -0.06 [-0.11 to -0.002]) while higher triclosan exposure was associated with a higher hCG (0.02 [0.003 to 0.04]). Higher exposure to several phthalates, including mono-ethyl and mono-butyl phthalates (MEP and MBP) as well as metabolites of di-2-ethylhexyl phthalate (DEHP) was associated with a lower hCG (beta [95% CI] for sum of DEHP metabolites: -0.13 [-0.19 to -0.07]). Likewise, higher exposure to several polychlorinated biphenyls (PCBs) was associated with a lower hCG. In the WQS regression, each quartile increase in the EDCs mixture was associated with -0.27 lower hCG (95% CI: -0.34 to -0.19). DISCUSSION: Higher exposure to several EDCs during pregnancy was associated with a lower hCG; and despite the small effect sizes, still indicating that the exposure may negatively affect production or secretion of hCG by the placenta. Our results provide the impetus for future experimental studies to investigate the placenta as a target organ for adverse effects of EDCs.

Prenatal exposure to phthalates and gender-specific play behavior at seven years of age in the SELMA study.

BACKGROUND: A growing body of evidence shows that prenatal exposure to phthalates affects child development. Since many phthalates have been shown to alter endocrine signaling, they may influence reproductive development, neurodevelopment, and child behavior. Indeed, a few studies reported associations between prenatal phthalate exposure and gender-specific play behavior. However, evidence for this relationship is limited, and previous findings are based on single phthalates, while human exposure entails mixtures of chemicals. OBJECTIVE: We aimed to investigate the associations between prenatal exposure to single phthalates, as well as a phthalate mixture, and gender-specific play behavior. METHODS: A total of 715 mother-child pairs from the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy (SELMA) study were included. In the median week 10 of pregnancy, phthalate metabolites were measured in urine. Gender-specific play behavior was measured with Preschool Activities Inventory at the age of seven years. Linear and weighted quantile sum regressions were used; data was stratified by sex. Models were adjusted for child and maternal age, maternal education, parental attitudes toward play behavior, and urinary creatinine concentration. RESULTS: For boys, single compound analyses revealed negative associations of prenatal exposure to di-isononyl phthalate (DINP) concentrations with masculine (ß = -1.44; 95% CI = -2.72, -0.16) and composite (ß = -1.43; 95% CI = -2.72, -0.13) scores. Suggestive associations were also observed with a mixture approach identifying DINP as the main contributor of the association of decreased masculine play. Among girls, higher urinary concentrations of 2,4-methyl-7-oxyooctyl-oxycarbonyl-cyclohexane carboxylic acid (MOiNCH) was associated with decreased feminine (ß = -1.59; 95% CI = -2.62, -0.57) and masculine scores (ß = -1.22; 95% CI = -2.14, -0.29), whereas the mixture analyses did not yield conclusive results for girls. CONCLUSION: Our findings suggest associations of prenatal exposure to DINP with decreased masculine play behavior in boys while the results for girls were not fully conclusive.

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.

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.

From Cohort to Cohort: A Similar Mixture Approach (SMACH) to Evaluate Exposures to a Mixture Leading to Thyroid-Mediated Neurodevelopmental Effects Using NHANES Data.

Prenatal exposure to a mixture (MIX N) of eight endocrine-disrupting chemicals has been associated with language delay in children in a Swedish pregnancy cohort. A novel approach was proposed linking this epidemiological association with experimental evidence, where the effect of MIX N on thyroid hormone signaling was assessed using the Xenopus eleuthero-embryonic thyroid assay (XETA OECD TG248). From this experimental data, a point of departure (PoD) was derived based on OECD guidance. Our aim in the current study was to use updated toxicokinetic models to compare exposures of women of reproductive age in the US population to MIX N using a Similar Mixture Approach (SMACH). Based on our findings, 66% of women of reproductive age in the US (roughly 38 million women) had exposures sufficiently similar to MIX N. For this subset, a Similar Mixture Risk Index (SMRIHI) was calculated comparing their exposures to the PoD. Women with SMRIHI > 1 represent 1.1 million women of reproductive age. Older women, Mexican American and other/multi race women were less likely to have high SMRIHI values compared to Non-Hispanic White women. These findings indicate that a reference mixture of chemicals identified in a Swedish cohort-and tested in an experimental model for establishment of (PoDs)-is also of health relevance in a US population.

Is WISC-IV Working Memory Index associated with ADHD symptoms in 7-8-year-olds?

The Working Memory Index (WMI) in the Wechsler Intelligence Scale for Children (WISC) has been suggested to be associated with ADHD symptoms. The relationship between WMI and ADHD symptoms in the general population is not clear. The study aimed to examine the association between working memory (WM) and behavioral regulation (BR), and hyperactivity/inattention (HI) in a general population sample of 7-8-year-olds, and whether general intellectual functioning is associated with BR and HI. The study also examined if those with low WMI also fulfill elevated ADHD criteria. The study group (N = 865) was assessed with the WISC (Fourth edition), the Behavior Rating Inventory of Executive Function, the Strengths and Difficulties Questionnaire, and the Five to Fifteen Questionnaire, and divided into three groups based on WM function, and in relation to BR and/or HI problems. The associations between WM and BR, and WM and HI, including intellectual functioning as covariate, were examined. WM deficits were found in 22%, but the majority of those had no BR or HI problems. Four percent in the study group had WM deficits combined with BR and/or HI problems, and in about one third of those inattentive ADHD criteria were fulfilled. WM and prosocial behavior were associated with BR and HI. WM deficits measured with WISC WMI in 7-8-year-olds do not always signal BR and/or HI problems.

A human-relevant mixture of endocrine disrupting chemicals induces changes in hippocampal DNA methylation correlating with hyperactive behavior in male mice.

Humans are ubiquitously exposed to endocrine disrupting chemicals (EDCs), substances that interfere with endogenous hormonal signaling. Exposure during early development is of particular concern due to the programming role of hormones during this period. A previous epidemiological study has shown association between prenatal co-exposure to 8 EDCs (Mixture N1) and language delay in children, suggesting an effect of this mixture on neurodevelopment. Furthermore, in utero exposure to Mixture N1 altered gene expression and behavior in adult mice. In this study, we investigated whether epigenetic mechanisms could underlie the long term effects of Mixture N1 on gene expression and behavior. To this end, we analyzed DNA methylation at regulatory regions of genes whose expression was affected by Mixture N1 in the hippocampus of in utero exposed mice using bisulfite-pyrosequencing. We show that Mixture N1 decreases DNA methylation in males at three genes that are part of the hypothalamus-pituitary-adrenal (HPA) axis: Nr3c1, Nr3c2, and Crhr1, coding for the glucocorticoid receptor, the mineralocorticoid receptor, and the corticotropin releasing hormone receptor 1, respectively. Furthermore, we show that the decrease in Nr3c1 methylation correlates with increased gene expression, and that Nr3c1, Nr3c2, and Crhr1 methylation correlates with hyperactivity and reduction in social behavior. These findings indicate that an EDC mixture corresponding to a human exposure scenario induces epigenetic changes, and thus programming effects, on the HPA axis that are reflected in the behavioral phenotypes of the adult male offspring.

Association of per- and polyfluoroalkyl substances with thyroid homeostasis during pregnancy in the SELMA study.

OBJECTIVES: To investigate the association of exposure to per- and polyfluoroalkyl substances (PFAS) during early pregnancy with markers of the maternal thyroid system. METHODS: Serum concentrations of seven PFAS as well as thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4), free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. Outcomes were concentrations of TSH and thyroid hormones, FT4/FT3 or TT4/TT3 ratios, TSH/FT4 ratio as a marker of the negative feedback loop, TT4/FT4 or TT3/FT3 ratios as markers of the binding of thyroid hormones to binding proteins. RESULTS: The study population comprised 2,008 women with median (95% range) gestational age of 10 (6-14) weeks. There was no association between PFAS and TSH. Higher PFNA, PFDA, PFHpA and PFOA levels were associated with a higher FT4 (largest effect estimate for PFDA: ß [95% CI]: 0.27 [0.10 to 0.45], P = 0.002). Higher PFUnDA levels, but no other PFAS, were associated with a lower FT3 (ß [95% CI]: -0.05 [-0.09 to -0.01], P = 0.005). Higher PFUnDA levels were associated with lower TT4 (ß [95% CI]: -1.58 [-3.07 to -0.09]) and there was an inverted U-shaped association of PFOS with TT4 (P = 0.03). Higher PFDA, PFUnDA, PFHpA levels were associated with a lower TT3. Overall, higher PFAS concentrations were associated with a higher FT4/FT3 ratio and a higher TT4/TT3 ratio. There was no association of PFAS with the TSH/FT4 ratio. Higher concentrations of several PFAS were associated with lower TT4/FT4 and TT3/FT3 ratios. CONCLUSIONS: These findings translate results from experimental studies suggesting that exposure to PFAS may interfere with the thyroid system during pregnancy. Further experimental studies should take into account human evidence to better understand the potential underlying mechanisms of thyroid disruption by PFAS exposure.

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.

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.

Using Metrics of a Mixture Effect and Nutrition from an Observational Study for Consideration towards Causal Inference.

Environmental exposures to a myriad of chemicals are associated with adverse health effects in humans, while good nutrition is associated with improved health. Single chemical in vivo and in vitro studies demonstrate causal links between the chemicals and outcomes, but such studies do not represent human exposure to environmental mixtures. One way of summarizing the effect of the joint action of chemical mixtures is through an empirically weighted index using weighted quantile sum (WQS) regression. My Nutrition Index (MNI) is a metric of overall dietary nutrition based on guideline values, including for pregnant women. Our objective is to demonstrate the use of an index as a metric for more causally linking human exposure to health outcomes using observational data. We use both a WQS index of 26 endocrine-disrupting chemicals (EDCs) and MNI using data from the SELMA pregnancy cohort to conduct causal inference using g-computation with counterfactuals for assumed either reduced prenatal EDC exposures or improved prenatal nutrition. Reducing the EDC exposure using the WQS index as a metric or improving dietary nutrition using MNI as a metric, the counterfactuals in a causal inference with one SD change indicate significant improvement in cognitive function. Evaluation of such a strategy may support decision makers for risk management of EDCs and individual choices for improving dietary nutrition.

From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures.

Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay.

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.

Prenatal phthalate exposure and early childhood wheeze in the SELMA study.

BACKGROUND: Prenatal maternal phthalate exposure has been associated with wheeze and asthma in children, but results are inconclusive. Previous studies typically assessed exposure in late pregnancy, included only a small number of old phthalates, and assessed outcomes in children aged 5 years or older. OBJECTIVE: We explored associations between 1st trimester prenatal maternal exposure to a wider range of phthalates and wheeze in early childhood. METHODS: First trimester concentrations of 14 metabolites from 8 phthalates and one alternative plasticizer were quantified in first-morning void urine from 1148 mothers in the Swedish SELMA study. Associations between log-transformed metabolite concentrations and parental reported ever wheeze among 24-month-old children were investigated with logistic regression models adjusted for parental asthma/rhinitis, sex of child, maternal education, smoking, and creatinine. RESULTS: Metabolites of replacement phthalates di-iso-decyl phthalate (DiDP) and di-2-propylheptyl phthalate (DPHP) were associated with increased risk for wheeze (aOR 1.47, 95% CI 1.08-2.01 and aOR 1.49, 95% CI 1.04-2.15, respectively). The associations with DiDP and DPHP were stronger among children whose parents did not have asthma or rhinitis. In this group, wheeze was also associated with metabolites of butyl-benzyl phthalate (BBzP) and di-iso-nonyl phthalate (DiNP). SIGNIFICANCE: Maternal phthalate exposure during early pregnancy may be a risk factor for wheeze in early childhood, especially among children whose parents do not have asthma or rhinitis symptoms.

Paracetamol use during pregnancy - a call for precautionary action.

Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders. Here we summarize this evidence and call for precautionary action through a focused research effort and by increasing awareness among health professionals and pregnant women. APAP is an important medication and alternatives for treatment of high fever and severe pain are limited. We recommend that pregnant women should be cautioned at the beginning of pregnancy to: forego APAP unless its use is medically indicated; consult with a physician or pharmacist if they are uncertain whether use is indicated and before using on a long-term basis; and minimize exposure by using the lowest effective dose for the shortest possible time. We suggest specific actions to implement these recommendations. This Consensus Statement reflects our concerns and is currently supported by 91 scientists, clinicians and public health professionals from across the globe.