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  • 1.
    Bornehag, Carl-Gustaf
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013). Icahn School of Medicine at Mount Sinai.
    Lindh, C.
    Lunds universitet.
    Reichenberg, A.
    Mount Sinai School of Medicine, New York.
    Wikström, S.
    Örebro University.
    Unenge Hallerbäck, Maria
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013).
    Evans, S. F.
    Icahn School of Medicine at Mount Sinai.
    Sathyanarayana, S.
    University of Washington, Seattle.
    Barrett, E. S.
    Rutgers School of Public Health, Piscataway, NJ.
    Nguyen, R. H. N.
    University of Minnesota.
    Bush, N. R.
    University of California, San Francisco.
    Swan, S. H.
    Icahn School of Medicine at Mount Sinai.
    Association of Prenatal Phthalate Exposure with Language Development in Early Childhood2018In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 172, no 12, p. 1169-1176Article in journal (Refereed)
    Abstract [en]

    Importance: Prenatal exposure to phthalates has been associated with neurodevelopmental outcomes, but little is known about the association with language development. Objective: To examine the association of prenatal phthalate exposure with language development in children in 2 population-based pregnancy cohort studies. Design, Setting, and Participants: Data for this study were obtained from the Swedish Environmental Longitudinal Mother and Child, Asthma and Allergy (SELMA) study conducted in prenatal clinics throughout Värmland county in Sweden and The Infant Development and the Environment Study (TIDES) conducted in 4 academic centers in the United States. Participants recruited into both studies were women in their first trimester of pregnancy who had literacy in Swedish (SELMA) or English or Spanish (TIDES). This study included mothers and their children from both the SELMA study (n = 963) and TIDES (n = 370) who had complete data on prenatal urinary phthalate metabolite levels, language delay, and modeled covariables. For SELMA, the data were collected from November 1, 2007, to June 30, 2013, and data analysis was conducted from November 1, 2016, to June 30, 2018. For TIDES, data collection began January 1, 2010, and ended March 29, 2016, and data analysis was performed from September 15, 2016, to June 30, 2018. Main Outcomes and Measures: Mothers completed a language development questionnaire that asked the number of words their children could understand or use at a median of 30 months of age (SELMA) and 37 months of age (TIDES). The responses were categorized as fewer than 25, 25 to 50, and more than 50 words, with 50 words or fewer classified as language delay. Results: In the SELMA study, 963 mothers, 455 (47.2%) girls, and 508 [52.8%] boys were included. In TIDES, 370 mothers, 185 (50.0%) girls, and 185 (50.0%) boys were included in this analysis. The prevalence of language delay was 10.0% in both SELMA (96 reported) and TIDES (37 reported), with higher rates of delay in boys than girls (SELMA: 69 [13.5%] vs 27 [6.0%]; TIDES: 12 [12.4%] vs 14 [7.6%]). In crude analyses, the metabolite levels of dibutyl phthalate and butyl benzyl phthalate were statistically significantly associated with language delay in both cohorts. In adjusted analyses, a doubling of prenatal exposure of dibutyl phthalate and butyl benzyl phthalate metabolites increased the odds ratio (OR) for language delay by approximately 25% to 40%, with statistically significant results in the SELMA study (dibutyl phthalate OR, 1.29 [95% CI, 1.03-1.63; P =.03]; butyl benzyl phthalate OR, 1.26 [95% CI, 1.07-1.49; P =.003]). A doubling of prenatal monoethyl phthalate exposure was associated with an approximately 15% increase in the OR for language delay in the SELMA study (OR, 1.14; 95% CI, 1.00-1.31; P =.05), but no such association was found in TIDES (OR, 0.98; 95% CI, 0.79-1.23). Conclusions and Relevance: In findings from this study, prenatal exposure to dibutyl phthalate and butyl benzyl phthalate was statistically significantly associated with language delay in children in both the SELMA study and TIDES. These findings, along with the prevalence of prenatal exposure to phthalates, the importance of language development, and the inconsistent results from a 2017 Danish study, suggest that the association of phthalates with language delay may warrant further examination.

  • 2.
    Bornehag, Carl-Gustaf
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013). Icahn School of Medicine at Mount Sinai, NY, USA.
    Reichenberg, Avi
    Icahn School of Medicine at Mount Sinai, NY, USA.
    Unenge Hallerbäck, Maria
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013).
    Wikström, Sverre
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013).
    Koch, Holger M.
    Institute of the Ruhr-University, Bochum, Germany.
    Jonsson, B. A.
    Lund University.
    Swan, Shanna H.
    Icahn School of Medicine at Mount Sinai, NY, USA.
    Prenatal exposure to acetaminophen and children's language development at 30 months2018In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 51, p. 98-103Article in journal (Refereed)
    Abstract [en]

    Objective: To examine prenatal APAP exposure in relation to language development in offspring at 30 months of age. Method: A population-based pregnancy cohort study including 754 women who enrolled in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study in pregnancy week 8-13. Two exposure measures were used: (1) maternally reported number of APAP tablets taken between conception and enrollment; (2) APAP urinary concentration at enrollment. Language development at 30 months was assessed by nurse's evaluation and parental questionnaire, including the number of words the child used (<25, 25-50 and >50). Main study outcome; parental report of use of fewer than 50 words, termed language delay (LD). Results: 59.2% of women enrolled in weeks 8-13 reported taking APAP between conception and enrollment. APAP was measurable in all urine samples and urinary APAP was correlated with the number of APAP taken during pregnancy (P < 0.01). Language delay was more prevalent in boys (12.6%) than girls (4.1%) (8.5% in total). Both the number of APAP tablets and urinary APAP concentration were associated with greater LD in girls but not in boys. The adjusted odds ratio (OR) for LD among girls whose mothers reported >6 vs. 0 APAP tablets was 5.92 (95% confidence interval (CI) 1.10-31.94). The OR for LD in girls whose mothers' urinary APAP was in the highest compared to the lowest quartile was 10.34 (95% CI 1.37-77.86). While it cannot be ruled out, our available data do not support confounding by indication. Conclusions: Given the prevalence of prenatal APAP use and the importance of language development, these findings, if replicated, would suggest that pregnant women should limit their use of this analgesic during pregnancy. (C) 2017 Elsevier Masson SAS. All rights reserved.

  • 3.
    Bornehag, Carl-Gustaf
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013). Icahn School of Medicine at Mount Sinai, NY, USA.
    Reichenberg, Avi
    Icahn School of Medicine at Mount Sinai, NY, USA.
    Unenge Hallerbäck, Maria
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013).
    Wikström, Sverre
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013).
    Koch, Holger M.
    Institute of the Ruhr-University, Bochum, Germany.
    Swan, Shanna H.
    Icahn School of Medicine at Mount Sinai, NY, USA.
    Reply to Shukla et al., Commentary on: Prenatal exposure to acetaminophen and children's language development at 30 months2018In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 51, p. 86-86Article in journal (Refereed)
  • 4.
    Tanner, Eva
    et al.
    Icahn School of Medicine at Mount Sinai, New York, NY, United State.
    Unenge Hallerbäck, Maria
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013).
    Wikström, Sverre
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013). Örebro Universitet.
    Lindh, Christian
    Lunds Universitet.
    Kiviranta, Hannu
    National Institute for Health and Welfare, Helsinki, Finland.
    Gennings, Chris
    Icahn School of Medicine at Mount Sinai, New York, NY, United State.
    Bornehag, Carl-Gustaf
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013). Icahn School of Medicine at Mount Sinai, New York, NY, United State.
    Early prenatal exposure to suspected endocrine disruptor mixtures is associated with lower IQ at age seven2020In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 134, p. 1-11, article id 105185Article in journal (Refereed)
    Abstract [en]

    Background: Endocrine disrupting chemicals (EDCs) are xenobiotics with the ability to interfere with hormone action, even at low levels. Prior environmental epidemiology studies link numerous suspected EDCs, including phthalates and bisphenol A (BPA), to adverse neurodevelopmental outcomes. However, results for some chemicals were inconsistent and most assessed one chemical at a time.

    Objectives: To evaluate the overall impact of prenatal exposure to an EDC mixture on neurodevelopment in school-aged children, and identify chemicals of concern while accounting for co-exposures.

    Methods: Among 718 mother-child pairs from the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA) study, we used Weighted Quantile Sum (WQS) regression to assess the association between 26 EDCs measured in 1st trimester urine or blood, with Wechsler Intelligence Scale for Children (IV) Intelligence Quotient (IQ) scores at age 7 years. Models were adjusted for child sex, gestational age, mother's education, mother's IQ (RAVEN), weight, and smoking status. To evaluate generalizability, we conducted repeated holdout validation, a machine learning technique.ResultsUsing repeated holdout validation, IQ scores were 1.9-points (CI = −3.6, −0.2) lower among boys for an inter-quartile-range (IQR) change in the WQS index. BPF made the largest contribution to the index with a weight of 14%. Other chemicals of concern and their weights included PBA (9%), TCP (9%), MEP (6%), MBzP (4%), PFOA (6%), PFOS (5%), PFHxS (4%), Triclosan (5%), and BPA (4%). While we did observe an inverse association between EDCs and IQ among all children when training and testing the WQS index estimate on the full dataset, these results were not robust to repeated holdout validation.

    Conclusion: Among boys, early prenatal exposure to EDCs was associated with lower intellectual functioning at age 7. We identified bisphenol F as the primary chemical of concern, suggesting that the BPA replacement compound may not be any safer for children. Future studies are needed to confirm the potential neurotoxicity of replacement analogues.

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