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3 Fluoride Exposure and Hypothyroidism in Pregnant Women: A Potential Mechanism of Fluoride Neurotoxicity
- Meaghan Hall, Bruce Lanphear, Jonathan Chevrier, Richard Hornung, Rivka Green, Carly Goodman, Pierre Ayotte, E. Angeles Martinez-Mier, Christine Till
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 866-867
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Objective:
Fluoride exposure has been associated with thyroid dysfunction, but fluoride's impact on thyroid function in pregnancy is unclear, especially during early gestation when the fetus is dependent on maternal thyroid hormone. We examined the potential thyroid-disrupting effects of maternal fluoride exposure in pregnancy and tested whether thyroid disruption in pregnancy mediates the association between maternal fluoride exposure and child intelligence quotient (IQ) among Canadian mother-child dyads living in areas with optimal fluoridation.
Participants and Methods:We measured fluoride concentrations in drinking water and in spot urine samples collected in each trimester from pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals study. We also measured thyroid hormone (thyroid stimulating hormone [TSH], free thyroxine [FT4], and total thyroxine [TT4]) levels during the first trimester of pregnancy and categorized women as euthyroid (n=1301), subclinical hypothyroid (n=100), or primary hypothyroid (n=28). Those categorized as primary hypothyroid were combined with an additional 79 women who reported clinical diagnoses at time of study enrolment (total n=107). In a sample of 1508 women, we used logistic regression to estimate the association between fluoride exposure and risk of either subclinical or primary hypothyroidism, separately, and linear regression to estimate associations between fluoride exposure and women's thyroid hormone levels (TSH, FT4, TT4). We tested effect modification by child sex and thyroid peroxidase (TPO) antibody status. In a subsample of 439 mother-child pairs, we measured child Full-Scale IQ (FSIQ) at 3-4 years of age using the Wechsler Preschool and Primary Scale of Intelligence. We used linear regression to test associations between maternal hypothyroidism or thyroid hormone levels, and children's FSIQ scores. Finally, mediation analysis in the counterfactual framework was used to estimate the proportion of the effect of maternal fluoride exposure on child FSIQ mediated by maternal hypothyroidism, through evaluation of the natural direct (not through hypothyroidism) and indirect (through hypothyroidism) effects.
Results:Using categorical measures of thyroid status, a 0.5 mg/L increase in water fluoride concentration was associated with a 1.64 (95% confidence interval [CI], 1.04 to 2.58) increased odds of primary hypothyroidism. This association was stronger among women with normal TPO antibody levels (< 5.61 IU/mL) (odds ratio, 2.80; 95% CI, 1.24 to 6.36). In contrast, we did not find a significant association between maternal urinary fluoride and hypothyroidism. For continuous measures of thyroid hormone levels, a 1 mg/L increase in maternal urinary fluoride was associated with a 35% (p=0.01) increase in TSH among women pregnant with a female fetus. In our subsample analyses, children born to women with primary hypothyroidism had lower FSIQ than children of euthyroid women, especially among boys (B, 8.78; 95% CI, -16.78 to -0.79). In contrast, maternal TSH, FT4, and TT4 levels were not significantly associated with child FSIQ scores. Maternal primary hypothyroidism did not significantly mediate the relationship between maternal water fluoride concentration and child FSIQ (p natural indirect effect= .35).
Conclusions:Fluoride in drinking water may increase the risk of hypothyroidism in pregnancy. Thyroid dysfunction in pregnancy may be one mechanism underlying developmental neurotoxicity of fluoride.
2 Sex difference of Developmental Neurotoxicants on Intellectual Abilities: A Systematic Review and Meta-Analysis
- Carly V Goodman, Rivka Green, Allya DaCosta, David Flora, Bruce Lanphear, Christine Till
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 865-866
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Objective:
Early life exposures to lead, mercury, polychlorinated biphenyls (PCBs), polybromide diphenyl ethers (PBDEs), organophosphate pesticides (OPPs), and phthalates have been associated with diminished IQ scores in children. Some studies suggest that these neurotoxicants impact boys and girls differently. We conducted a systematic review and meta-analysis to identify and quantify sex differences in IQ deficits from pre- and post-natal exposures to these developmental neurotoxicants.
Participants and Methods:We used PubMed and PsychINFO to screen abstracts of articles published between January 1, 1950 and December 31, 2021 for empirical studies of six neurotoxicants [lead, mercury, PCBs, PBDEs, OPPs, and/or phthalates] that (1) used an individualized biomarker; (2) measured exposure during the prenatal period or within the first six years of life; and (3) provided different effect estimates on children's intellectual abilities by sex. We assessed each study for risk of bias using Navigation Guide (Woodruff & Sutton, 2014). For studies with combinable data, we performed separate random effects meta-analyses for boys and girls with subgroup analyses by neurotoxicant. To homogenize the magnitude of effect observed in each study, we recalculated results to be expressed as the absolute change in intellectual abilities for a relative change of 1.5 times (i.e., 50% increase) in the exposure variable.
Results:Of 3205 studies screened, 53 met inclusion criteria: 34 evaluated prenatal exposure, 11 postnatal exposure, and 8 both pre- and post-natal exposure. We generally rated these studies as "low" to "probably low" risk of bias. Among the studies examining prenatal exposure, 27 reported no significant differences between the sexes, 7 found negative associations in boys, 4 found negative associations in girls, 5 found negative nonsignificant associations in boys and positive nonsignificant associations in girls, and 3 found no clear pattern, where differences by sex depended on the specific phthalate compound or outcome measurement. Among the studies examining postnatal exposure, 14 reported no significant differences between the sexes, 1 found a negative association in boys, 2 found negative associations in girls, and 2 found positive associations for either boys or girls. In our meta-analysis of 16 studies (4 lead, 4 mercury, 2 PBDEs, 2 OPPs, 4 phthalates), we found that prenatal exposure to developmental neurotoxicants was associated with decreased full-scale intelligence in boys (B = -0.26; 95% CI: -0.45, -0.08), but not girls (B = 0.09; 95% CI: -0.14, 0.31). In subgroup analyses by neurotoxicant, prenatal exposure to lead (B = -1.07; 95% CI: -1.63, -0.52), and ZPBDEs (B = -0.57; 95% CI: -1.14, -0.01) were associated with decreased full-scale intelligence in boys, whereas the girls' effect sizes were consistently near zero.
Conclusions:During fetal development, boys appear to be more vulnerable than girls to IQ deficits from neurotoxic exposures, and especially from lead and PBDEs. More research is needed to examine the nuanced sex-specific effects found for postnatal exposures to toxic chemicals.
87 Suitability of the I-InTERACT-North Parenting Program for families with autistic children
- Rachael Lyon, Rivka Green, Angela Deotto, Giulia F Fabiano, Elizabeth Kelley, Evdokia Anagnostou, Rob Nicolson, Shari L Wade, Tricia S Williams
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 188
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Objective:
I-InTERACT-North is a stepped-care telepsychological parenting intervention designed to promote positive parenting skills and improve child behaviour. Initially developed for children with traumatic brain injury, our pilot study has shown efficacy in increasing positive parenting skills and reducing problem behaviours for children with early brain injury (e.g., stroke, encephalopathy). Recently, the program has expanded to include children with neurodevelopmental disorders, including Autism Spectrum Disorder. Although positive parenting programs (e.g., Parent-Child Interaction Therapy) can be effective for autistic children, it is unknown whether the goals most important to these families can be addressed with IInTERACT-North program. An examination of suitability and preliminary efficacy was conducted.
Participants and Methods:Parent participants of autistic children between 3 and 9 years (n= 20) were recruited from the neonatal, neurology, psychiatry, or cardiology clinics at The Hospital for Sick Children and the Province of Ontario Neurodevelopmental Disorders (POND) Network. Top problems, as reported by parents at baseline, were analyzed qualitatively through a cross-case analysis procedure in order to identify common themes and facilitate generalizations surrounding concerning behaviours. Parent-reported intensity of their children’s top problem behaviours on a scale from 1 (“not a problem”) to 8 (“huge problem”) were quantified. To explore preliminary program efficacy, t-tests were used to compare pre- and post-intervention problems and intensity on the Eyberg Child Behavior Inventory (ECBI) (n=16).
Results:A total of 56 top problem data units were examined, with convergent thematic coding on 53 of 56 (94.6% inter-coder reliability). Four prevalent, high-agreement themes were retained: emotion dysregulation (19; 33.9%), non-compliance (12; 21.4%), sibling conflict (7; 12.5%), and inattention and hyperactivity (7; 12.5%). Average problem intensity for these themes ranged from 5.85 to 6.53 (where 8 is greatest impairment) with emotion dysregulation having the highest intensity (6.53) compared to the others. Scores on the ECBI were lower post-intervention (Intensity scale: M= 59.06, SD= 8.1; Problem scale: M= 60.69, SD= 11.5) compared to pre-intervention (Intensity scale: M= 61.19, SD= 10.4; Problem scale: M= 64.31, SD= 11.7), but small sample size precluded detecting statistical significance (p’s = .16 and .07, respectively).
Conclusions:Thematic analysis of top problems identified by parents of autistic children suggested that concerns were transdiagnostic in nature, and represent common treatment targets of the I-InTERACTNorth program. Though challenging behaviours related to restricted interests or repetitive behaviours may exist in our sample, parental behavioural goals appeared to align with the types of concerns traditionally raised by participants of the program, supporting a transdiagnostic approach. Preliminary data point to positive treatment outcomes in these families.
5 Translating developmental neurotoxicity for the public: A large, international, randomized-control trial investigating children's environmental health literacy
- Rivka Green, Christine Till, Allya DaCosta, Jana El-Sabbagh, Carly Goodman, David Flora, Erica Phipps, Bruce Lanphear
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 868-869
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Objective:
Exposure to toxic chemicals during early brain development increases the risk of neurodevelopmental problems in children. Parents' and prospective parents' understanding of the impact of toxic chemicals on brain development and the efficacy of translation tools for children's environmental health literacy are poorly understood. We developed and validated a questionnaire, PRevention of Toxic chemicals in the Environment for Children Tool (PRoTECT) to assess knowledge of toxic chemicals and neurodevelopment, intentions to reduce exposures to toxic chemicals, and preferences for actions by government and industry to prevent neurodevelopmental disorders. Using PRoTECT, we surveyed people of child-bearing age across five countries (Canada, United States (US), United Kingdom (UK), India, and Australia) to identify general patterns of responses on this questionnaire by demographic characteristics, including country, age, gender, parental status, pregnancy status, and education. We also employed a randomized control design to examine the efficacy of a knowledge translation video to instill knowledge and prompt behavioral changes to reduce exposures to toxic chemicals immediately following its presentation and after a six-week follow-up period.
Participants and Methods:We recruited 15,594 participants, ages 18 to 45, via CloudResearch's Prime Panels between October-December 2021. After completing the PRoTECT survey, participants were randomly assigned to watch the video Little Things Matter: Impact of Toxic Chemicals on Brain Development (i.e., the experimental group) or to serve as the control group. Next, both groups answered a series of questions to assess their knowledge of toxic chemicals, their intentions to reduce exposures to toxic chemicals, and barriers to changing their behaviours. After six-weeks, we recontacted a subset (N=4,842) of participants to repeat PRoTECT and answer the same series of behavioural questions assessing whether they modified any of their behaviours to reduce exposure and why or why not.
Results:Most participants (i.e., 75-85%) agreed that toxic chemicals can impact brain development and endorsed preferences (∼85%) for allocating more resources to prevent neurodevelopmental disorders, especially people with higher education, parents and pregnant women, and people who lived in India. Despite this, a large proportion of participants (∼50%) trusted industry and believed that government effectively regulated toxic chemicals. After the six-week follow-up, experimental participants showed greater changes in scores on PRoTECT (i.e., between 5-15% change), indicating greater knowledge about harms posed by toxic chemicals, more intentions to reduce exposure, and stronger preferences for prevention as compared to the control group. Differences were larger among people from the US, those who were more highly educated, and people in their thirties. However, the differences between groups in making behavioural changes to reduce exposures were attenuated at the six-week follow up as compared to baseline. Significant barriers to reduce exposure to toxic chemicals were reported by both groups and included cost, inconvenience, and not knowing how to determine whether a product is non-toxic or where to purchase non-toxic products.
Conclusions:We observed greater knowledge and concerns about toxic chemicals among more affluent respondents, pregnant women and parents, and people living in India across both groups. While the video enhanced participants' knowledge about toxic chemicals and intentions to reduce exposure, they indicated that barriers hindered them from making behavioral changes.
Education effects on cognitive function in a healthy aged Arab population
- Rivka Inzelberg, Edna Schechtman, Amin Abuful, Magda Masarwa, Aziz Mazarib, Rosa Strugatsky, Lindsay A. Farrer, Robert C. Green, Robert P. Friedland
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- Journal:
- International Psychogeriatrics / Volume 19 / Issue 3 / June 2007
- Published online by Cambridge University Press:
- 20 October 2006, pp. 593-603
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Background: The Mini-mental State Examination (MMSE) has not been validated in Arabic speaking populations. The Brookdale Cognitive Screening Test (BCST) has been developed for use in low schooling populations. We investigated the influence of gender, education and occupation in a cognitively normal community sample which was assessed using an Arabic translation of the MMSE and the BCST.
Methods: Cognitively normal subjects (n = 266, 59.4% males, mean age (SD): 72.4 (5.5) years) from an Arab community in northern Israel (Wadi Ara) were evaluated. Education was categorized into levels: 1 = 0–4 years, 2 = 5–8 years, 3 = 9–12 years. Effects of gender, education and occupation on MMSE and BCST were analyzed by ANOVA, taking age as a covariate.
Results: The mean MMSE score of males [26.3 (4.1)] was higher than that of females [23.6 (4.2) points]. Two-way ANOVA showed a significant interaction between gender and education on MMSE (p = 0.0017) and BCST scores (p = 0.0002). The effect of gender on MMSE and BCST was significant in education level 1 (p < 0.0001, both tests) and level 2 (p < 0.05, both tests). For education level 1, MMSE and BCST scores were higher for males, while both scores were higher for females in education level 2. The effect of occupation was not significant for both genders.
Conclusion: Education and gender influence performance when using the Arabic translation of the MMSE and BCST in cognitively normal elderly. Cognitively normal females with 0–4 years of education scored lower than males. These results should be taken into consideration in the daily use of these instruments in Arabic.