Prenatal Phthalates, Maternal Thyroid Function, and Risk of Attention-Deficit Hyperactivity Disorder in the Norwegian Mother and Child Cohort

Engel, Stephanie M.; Villanger, Gro Dehli; Nethery, Rachel C.; Thomsen, Cathrine; Sakhi, Amrit Kaur; Drover, S.S.M.; Hoppin, Jane A.; Zeiner, Pål; Knudsen, Gun Peggy; Reichborn‐Kjennerud, Ted; Herring, Amy H.; Aase, Heidi

doi:10.1289/ehp2358

Cited by 96 publications

(84 citation statements)

References 86 publications

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“…In the first study, we selected 506 ADHD cases and 657 controls, frequency matched on birth year and sex to the case group. The second study included 199 ADHD cases and 529 controls matched on birth year but not sex (see Engel et al). Because of this slight difference in selection methods, all analyses were adjusted for or stratified by child sex.…”

Section: Methodsmentioning

confidence: 99%

Neonatal thyroid‐stimulating hormone and association with attention‐deficit/hyperactivity disorder

Villanger

Ystrøm

Engel

et al. 2020

Paediatric Perinatal Epid

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Background Normal brain development is dependent on maternal, fetal and neonatal thyroid function. Measuring neonatal thyroid‐stimulating hormone (TSH) 48‐72 hours after birth screens for congenital hypothyroidism, allowing early treatment to avoid serious impairment. However, even within sub‐clinical ranges, disrupted thyroid homeostasis during brain development has been linked to adverse neurodevelopmental outcomes, including attention‐deficit/hyperactivity disorder (ADHD). Objectives To estimate the association between neonatal TSH below threshold for potential congenital hypothyroidism and subsequent ADHD diagnosis using a population‐based birth cohort. Methods Children with a diagnosis of ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa) were identified through linkage with the Norwegian Patient Registry using ICD‐10 codes for hyperkinetic disorders. The study included 405 ADHD cases and 1,092 controls (born 2003‐2008) with available neonatal TSH concentrations below 10 mU/L (cut‐off for potential congenital hypothyroidism) measured in dried blood spots sampled 48‐72 hours after birth. Results In multivariable, quintile models the relationship appeared to follow a U‐shaped pattern with elevated odds ratios (OR) at lower and higher TSH levels. Among children with TSH in the lowest quintile, odds of ADHD was approximately 1.5‐fold higher than children in the middle quintile (OR 1.60, 95% CI 1.09, 2.34), which was driven by substantially elevated risk among girls, with no association among boys (Pinteraction = 0.02; girls OR 3.10, 95% CI 1.53, 6.30; boys OR 1.16, 95% CI 0.73, 1.84). Conclusions ADHD risk appeared to be elevated among newborns with low TSH levels (i.e. with hyperthyroid status), and this association was mainly found among girls. Because our findings are suggestive of increased risk at very low TSH concentrations, where analytical accuracy is low, future studies should employ highly sensitive assays capable of accurate quantitation at very low concentrations. Also, larger studies are needed to investigate these associations at higher neonatal TSH concentrations where data are more widely distributed.

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Section: Methodsmentioning

confidence: 99%

Neonatal thyroid‐stimulating hormone and association with attention‐deficit/hyperactivity disorder

Villanger

Ystrøm

Engel

et al. 2020

Paediatric Perinatal Epid

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“…Epidemiological studies suggest that phthalate exposure during pregnancy is associated with increased risk of pregnancy loss, preeclampsia, preterm birth, and gestational hypertension [3][4][5][6][7][8][9]. In addition, gestational phthalate exposure has been associated with altered neurodevelopment [10][11][12][13], endocrine, reproductive [14][15][16][17][18], and cardiometabolic outcomes during infancy and childhood [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Determinants and characterization of exposure to phthalates, DEHTP and DINCH among pregnant women in the PROTECT birth cohort in Puerto Rico

Rodríguez‐Carmona

Ashrap

Calafat

et al. 2019

J Expo Sci Environ Epidemiol

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Background As a result of evidence suggesting phthalate toxicity, their use has decreased in recent years. However, new phthalates and non-phthalate replacements have emerged in their place, with unknown potential impacts on health. Methods We measured 15 phthalate, two di(2-ethylhexyl)terephthalate (DEHTP), and two di(isononyl)cyclohexane-1,2dicarboxylate (DINCH) urinary metabolites, collected up to three times during pregnancy from 994 women in Northern Puerto Rico (2011-2017). We used tests of linear trend to assess changes in concentrations over time and linear mixed models to identify predictors of exposure (sociodemographic characteristics, drinking water sources, diet, product use). Results Several phthalate metabolites decreased over the study period indicating decreased exposure, while the geometric mean of DEHTP metabolites (molecular sum) increased threefold between 2014 and 2017. Intraclass correlations revealed low to moderate reproducibility of these biomarkers across pregnancy. Several metabolites were associated with maternal age, income, education, pre-pregnancy BMI, drinking public water, use of cleaning and personal care products, and ice cream consumption. DINCH metabolite concentrations remained low throughout the study period. Conclusion Although exposure to some phthalates may be decreasing, exposure to replacements, such as DEHTP, is increasing. Additional studies are needed to further characterize sources of phthalate replacement chemicals and potential exposure-related health effects among vulnerable populations.

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“…Thus, it is hypothesized that prenatal exposure to phthalates might contribute to risk of childhood neurodevelopmental disorders. Among children 8–11 years of age, urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites were significantly associated with attention deficit hyperactivity disorder (ADHD) [ 33 , 34 ]. Other studies also found that having PVC flooring (a source of certain phthalates) in a parent’s bedroom during pregnancy and child’s first year was associated with an increased risk of ASD [ 35 ] and that higher indoor dust concentrations of diethyl phthalate (DEP) and dibutyl phthalate (DBP) were associated with greater hyperactivity-impulsivity and inattention among ASD children [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Prenatal exposure to phthalates and autism spectrum disorder in the MARBLES study

et al. 2018

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BackgroundEvidence from experimental and observational studies suggests that prenatal phthalate exposures may be associated with autism spectrum disorder (ASD). We examined whether prenatal phthalate exposures were associated with an increased risk of ASD.MethodsWe quantified 14 metabolites of eight phthalates in 636 multiple maternal urine samples collected during 2nd and 3rd trimesters of pregnancy from 201 mother-child pairs in MARBLES (Markers of Autism Risk in Babies – Learning Early Signs), a high-risk ASD longitudinal cohort. At 3 years old, children were clinically assessed for ASD and classified into three diagnostic categories: ASD (n = 46), non-typical development (Non-TD, n = 55), and typical development (TD, n = 100). We used multinomial logistic regression to evaluate the association of phthalate metabolite concentrations with ASD and Non-TD.ResultsMost associations of phthalate biomarkers with both ASD and Non-TD were null, with the exception that monoethyl phthalate (MEP) was significantly associated with an increased risk of Non-TD (per 2.72-fold relative increase in concentration: Relative risk ratio (RRR) = 1.38; 95% confidence interval (CI): 1.01, 1.90). When stratified by prenatal vitamin use during the first month of pregnancy, among mothers who took vitamins, ASD risk was inversely associated with mono-isobutyl phthalate (MiBP, RRR = 0.44; 95% CI: 0.21, 0.88), mono(3-carboxypropyl) phthalate (MCPP, RRR = 0.41; 95% CI: 0.20, 0.83) and mono-carboxyisooctyl phthalate (MCOP, RRR = 0.49; 95% CI: 0.27, 0.88), but among mothers who did not take prenatal vitamins, Non-TD risk was positively associated with MCPP (RRR = 5.09; 95% CI: 2.05, 12.6), MCOP (RRR = 1.86; 95% CI: 1.01, 3.39), and mono-carboxyisononyl phthalate (MCNP, RRR = 3.67; 95% CI: 1.80, 7.48). When stratified by sex, among boys, MEP, monobenzyl phthalate, MCPP, MCNP, and sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP) were positively associated with Non-TD risk, but associations with ASD were null. Among girls, associations with both ASD and Non-TD were null.ConclusionsOur study showed that phthalate exposures in mid- to late pregnancy were not associated with ASD in children from this high-risk ASD cohort. Further studies should be conducted in the general population without high-risk genes to confirm our findings.Electronic supplementary materialThe online version of this article (10.1186/s12940-018-0428-4) contains supplementary material, which is available to authorized users.

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Prenatal Phthalates, Maternal Thyroid Function, and Risk of Attention-Deficit Hyperactivity Disorder in the Norwegian Mother and Child Cohort

Cited by 96 publications

References 86 publications

Neonatal thyroid‐stimulating hormone and association with attention‐deficit/hyperactivity disorder

Neonatal thyroid‐stimulating hormone and association with attention‐deficit/hyperactivity disorder

Determinants and characterization of exposure to phthalates, DEHTP and DINCH among pregnant women in the PROTECT birth cohort in Puerto Rico

Prenatal exposure to phthalates and autism spectrum disorder in the MARBLES study

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