Fluoride exposure has the potential to disrupt thyroid functioning, though adequate iodine intake may mitigate this effect. This is the first population-based study to examine the impact of chronic ...low-level fluoride exposure on thyroid function, while considering iodine status. The objective of this study was to determine whether urinary iodine status modifies the effect of fluoride exposure on thyroid stimulating hormone (TSH) levels.
This cross-sectional study utilized weighted population-based data from Cycle 3 (2012−2013) of the Canadian Health Measures Survey (CHMS). Information was collected via a home interview and a visit to a mobile examination centre. The weighted sample represented 6,914,124 adults in Canada aged 18–79 who were not taking any thyroid-related medication. Urinary fluoride concentrations were measured in spot samples using an ion selective electrode and adjusted for specific gravity (UFSG). Serum TSH levels provided a measure of thyroid function. Multivariable regression analyses examined the relationship between UFSG and TSH, controlling for covariates.
Approximately 17.8% of participants fell in the moderately-to-severely iodine deficient range. The mean (SD) age of the sample was 46.5 (15.6) years and the median UFSG concentration was 0.74 mg/L. Among iodine deficient adults, a 1 mg/L increase in UFSG was associated with a 0.35 mIU/L increase in TSH 95% CI: 0.06, 0.64; p = 0.01, one-tailed.
Adults living in Canada who have moderate-to-severe iodine deficiencies and higher levels of urinary fluoride may be at an increased risk for underactive thyroid gland activity.
•Higher urinary fluoride levels are not associated with higher TSH levels in the general population of adults living in Canada.•Iodine status modifies the relationship between urinary fluoride and TSH levels.•Adults in Canada who have moderate-to-severe iodine deficiencies and higher urinary fluoride tend to have higher TSH levels.
•Consumption of formula reconstituted with fluoridated water can lead to excessive fluoride intake.•Breastfed infants receive very low intake of fluoride.•We compared IQ scores in 398 children who ...were formula-fed versus breastfed during infancy.•IQ scores were lower with higher levels of fluoride in tap water.•The effect was more pronounced among formula-fed children, especially for nonverbal skills.
Infant consumption of formula reconstituted with fluoridated water can lead to excessive fluoride intake. We examined the association between fluoride exposure in infancy and intellectual ability in children who lived in fluoridated or non-fluoridated cities in Canada.
We examined 398 mother-child dyads in the Maternal-Infant Research on Environmental Chemicals cohort who reported drinking tap water. We estimated water fluoride concentration using municipal water reports. We used linear regression to analyze the association between fluoride exposure and IQ scores, measured by the Wechsler Primary and Preschool Scale of Intelligence-III at 3–4 years. We examined whether feeding status (breast-fed versus formula-fed) modified the impact of water fluoride and if fluoride exposure during fetal development attenuated this effect. A second model estimated the association between fluoride intake from formula and child IQ.
Thirty-eight percent of mother-child dyads lived in fluoridated communities. An increase of 0.5 mg/L in water fluoride concentration (approximately equaling the difference between fluoridated and non-fluoridated regions) corresponded to a 9.3- and 6.2-point decrement in Performance IQ among formula-fed (95% CI: −13.77, −4.76) and breast-fed children (95% CI: −10.45, −1.94). The association between water fluoride concentration and Performance IQ remained significant after controlling for fetal fluoride exposure among formula-fed (B = −7.93, 95% CI: −12.84, −3.01) and breastfed children (B = −6.30, 95% CI: −10.92, −1.68). A 0.5 mg increase in fluoride intake from infant formula corresponded to an 8.8-point decrement in Performance IQ (95% CI: −14.18, −3.34) and this association remained significant after controlling for fetal fluoride exposure (B = −7.62, 95% CI: −13.64, −1.60).
Exposure to increasing levels of fluoride in tap water was associated with diminished non-verbal intellectual abilities; the effect was more pronounced among formula-fed children.
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•Fluoride may disrupt thyroid function in pregnant women.•Fluoride exposure was associated with alterations in maternal thyroid hormone levels.•Urinary fluoride was associated with ...significantly higher TSH among those pregnant with females.•Adjustment for maternal iodine status did not change the results.
Fluoride exposure may increase the risk of hypothyroidism, but results from previous studies are inconsistent at low-level fluoride exposure (i.e., ≤0.7 mg/L). Human studies of fluoride and thyroid hormone levels in pregnancy are scarce.
We examined associations between fluoride exposure and maternal thyroid hormone levels in a Canadian pregnancy cohort, with consideration for fetal sex-specific effects.
We measured fluoride concentrations in drinking water and spot urine samples collected during each trimester from 1876 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. We also measured maternal thyroid stimulating hormone (TSH), free thyroxine (FT4), and total thyroxine (TT4) levels during the first trimester of pregnancy. We used linear and non-linear regression models to estimate associations between fluoride exposure and levels of TSH, FT4, and TT4. We explored effect modification by fetal sex and considered maternal iodine status as a potential confounder.
A 1 mg/L increase in urinary fluoride was associated with a 0.30 (95 %CI: 0.08, 0.51) logarithmic unit (i.e., 35.0 %) increase in TSH among women pregnant with females, but not males (B = 0.02; 95 %CI: −0.16, 0.19). Relative to women with urinary fluoride concentrations in the first quartile (0.05–0.32 mg/L), those with levels in the third quartile (0.49–0.75 mg/L) had higher FT4 and TT4 (i.e., inverted J-shaped associations), but the association was not statistically significant after adjustment for covariates (p = 0.06). Water fluoride concentration showed a U-shaped association with maternal FT4, whereby women with water fluoride concentrations in the second (0.13–0.52 mg/L) and third (0.52–0.62 mg/L) quartiles had significantly lower FT4 compared to those with levels in the first quartile (0.04–0.13 mg/L). Adjustment for maternal iodine status did not change the results.
Fluoride exposure was associated with alterations in maternal thyroid hormone levels, the magnitude of which appeared to vary by fetal sex. Given the importance of maternal thyroid hormones for fetal neurodevelopment, replication of findings is warranted.
•UFSG did not significantly predict ADHD diagnosis or ADHD-type symptoms.•Higher tap water fluoride was associated with higher odds of an ADHD diagnosis.•Higher water fluoride was associated with ...more ADHD-type symptoms for adolescents.•Adolescents living in a fluoridated region had higher odds of an ADHD diagnosis.•Adolescents living in fluoridated regions had more ADHD-type symptoms.
Exposure to fluoride has been linked with increased prevalence of attention deficit hyperactivity disorder (ADHD) in the United States and symptoms of inattention in Mexican children. We examined the association between fluoride exposure and attention outcomes among youth living in Canada.
We used cross-sectional data collected from youth 6 to 17 years of age from the Canadian Health Measures Survey (Cycles 2 and 3). Urinary fluoride concentration adjusted for specific gravity (UFSG) was available for 1877 participants. Water fluoride concentration measured in tap water samples was available for 980 participants. Community water fluoridation (CWF) status was determined by viewing reports on each city’s website or contacting the water treatment plant. We used logistic regression to test the association between the three measures of fluoride exposure and ADHD diagnosis. Linear regression was used to examine the relationship between the three measures of fluoride exposure and the hyperactivity/inattention score on the Strengths and Difficulties Questionnaire (SDQ).
UFSG did not significantly predict ADHD diagnosis or hyperactive/inattentive symptoms. A 1 mg/L increase in tap water fluoride level was associated with a 6.1 times higher odds of an ADHD diagnosis (95% CI = 1.60, 22.8). A significant interaction between age and tap water fluoride level (p = .03) indicated a stronger association between tap water fluoride and hyperactivity/inattention symptoms among older youth. A 1 mg/L increase in water fluoride level was associated with a 1.5 SDQ score increase (95% CI: 0.23, 2.68, p = .02) for youth at the 75th percentile of age (14 years old). Similarly, there was a significant interaction between age and CWF. At the 75th percentile of age (14 years old), those living in a fluoridated region had a 0.7-point higher SDQ score (95% CI = 0.34, 1.06, p < .01) and the predicted odds of an ADHD diagnosis was 2.8 times greater compared with youth in a non-fluoridated region (aOR = 2.84, 95% CI: 1.40, 5.76, p < .01).
Exposure to higher levels of fluoride in tap water is associated with an increased risk of ADHD symptoms and diagnosis of ADHD among Canadian youth, particularly among adolescents. Prospective studies are needed to confirm these results.
Epidemiologic and animal-based studies have raised concern over the potential impact of fluoride exposure on neurobehavioral development as manifested by lower IQ and deficits in attention. To date, ...no prospective epidemiologic studies have examined the effects of prenatal fluoride exposure on behavioral outcomes using fluoride biomarkers and sensitive measures of attention.
We aimed to examine the association between prenatal fluoride exposure and symptoms associated with attention-deficit/hyperactivity disorder (ADHD).
213 Mexican mother-children pairs of the Early Life Exposures to Environmental Toxicants (ELEMENT) birth cohort study had available maternal urinary samples during pregnancy and child assessments of ADHD-like behaviors at age 6–12. We measured urinary fluoride levels adjusted for creatinine (MUFcr) in spot urine samples collected during pregnancy. The Conners' Rating Scales-Revised (CRS-R) was completed by mothers, and the Conners' Continuous Performance Test (CPT-II) was administered to the children.
Mean MUFcr was 0.85 mg/L (SD = 0.33) and the Interquartile Range (IQR) was 0.46 mg/L. In multivariable adjusted models using gamma regression, a 0.5 mg/L higher MUFcr (approximately one IQR higher) corresponded with significantly higher scores on the CRS-R for DSM-IV Inattention (2.84 points, 95% CI: 0.84, 4.84) and DSM-IV ADHD Total Index (2.38 points, 95% CI: 0.42, 4.34), as well as the following symptom scales: Cognitive Problems and Inattention (2.54 points, 95% CI: 0.44, 4.63) and ADHD Index (2.47 points; 95% CI: 0.43, 4.50). The shape of the associations suggested a possible celling effect of the exposure. No significant associations were found with outcomes on the CPT-II or on symptom scales assessing hyperactivity.
Higher levels of fluoride exposure during pregnancy were associated with global measures of ADHD and more symptoms of inattention as measured by the CRS-R in the offspring.
•We measured urinary fluoride in 213 pregnant women living in Mexico City who were part of the ELEMENT pregnancy cohort study.•Higher concentration of maternal urinary fluoride was associated with more ADHD-like symptoms in school-age children.•Prenatal exposure to fluoride was most strongly associated with behavioral ratings of inattention, but not hyperactivity and impulse control.•Findings are consistent with the growing body of evidence suggesting neurotoxicity of early-life exposure to fluoride.
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•This is the first study to examine associations between prenatal fluoride exposure and disruptions to visual acuity and cardiac autonomic function in infants.•In this Canadian ...pregnancy cohort, prenatal fluoride exposure was linked to poorer visual acuity.•Prenatal fluoride exposure was linked to lower heart rate variability (root mean square of successive differences)•Results suggest that prenatal fluoride exposure may be associated with poorer central and peripheral markers of nervous system functioning in infant offspring.
Prenatal fluoride exposure can have adverse effects on children’s development; however, associations with visual and cardiac autonomic nervous system functioning are unknown. We examined associations between prenatal fluoride exposure and visual acuity and heart rate variability (HRV) in 6-month-old infants.
We used data from Canadian mother-infant pairs participating in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort. We estimated prenatal fluoride exposure using: i) fluoride concentration in drinking water (mg/L), ii) maternal urinary fluoride adjusted for specific gravity (MUFSG; mg/L) and averaged across pregnancy, and iii) maternal fluoride intake (µg/kg/day) from consumption of water, tea, and coffee, adjusted for maternal body weight (kg). We used multivariable linear regression to examine associations between each measure of fluoride exposure and Teller Acuity Card visual acuity scores (n = 435) and assessed HRV (n = 400) using two measures: root mean square of successive differences (RMSSD) and the standard deviation of N-N intervals (SDNN) measured at 6-months of age.
Median (IQR) values for water fluoride, MUFSG, and daily fluoride intake were 0.20 (IQR: 0.13–0.56) mg/L; 0.44 (0.28–0.70) mg/L and 4.82 (2.58–10.83) µg/kg/day, respectively. After adjustment for confounding variables, water fluoride concentration was associated with poorer infant visual acuity (B = -1.51; 95 % CI: −2.14,-0.88) and HRV as indicated by lower RMSSD (B = -1.60; 95 % CI: −2.74,-0.46) but not SDNN. Maternal fluoride intake was also associated with poorer visual acuity (B = -0.82; 95 % CI: −1.35,-0.29) and lower RMSSD (B = -1.22; 95 % CI: −2.15,-0.30). No significant associations were observed between MUFSG and visual acuity or HRV.
Fluoride in drinking water was associated with reduced visual acuity and alterations in cardiac autonomic function in infancy, adding to the growing body of evidence suggesting fluoride's developmental neurotoxicity.
Early life exposure to lead, mercury, polychlorinated biphenyls (PCBs), polybromide diphenyl ethers (PBDEs), organophosphate pesticides (OPPs), and phthalates have been associated with lowered IQ in ...children. In some studies, these neurotoxicants impact males and females differently. We aimed to examine the sex-specific effects of exposure to developmental neurotoxicants on intelligence (IQ) in a systematic review and meta-analysis.
We screened abstracts published in PsychINFO and PubMed before December 31st, 2021, for empirical studies of six neurotoxicants (lead, mercury, PCBs, PBDEs, OPPs, and phthalates) that (1) used an individualized biomarker; (2) measured exposure during the prenatal period or before age six; and (3) provided effect estimates on general, nonverbal, and/or verbal IQ by sex. We assessed each study for risk of bias and evaluated the certainty of the evidence using Navigation Guide. We performed separate random effect meta-analyses by sex and timing of exposure with subgroup analyses by neurotoxicant.
Fifty-one studies were included in the systematic review and 20 in the meta-analysis. Prenatal exposure to developmental neurotoxicants was associated with decreased general and nonverbal IQ in males, especially for lead. No significant effects were found for verbal IQ, or postnatal lead exposure and general IQ. Due to the limited number of studies, we were unable to analyze postnatal effects of any of the other neurotoxicants.
During fetal development, males may be more vulnerable than females to general and nonverbal intellectual deficits from neurotoxic exposures, especially from lead. More research is needed to examine the nuanced sex-specific effects found for postnatal exposure to toxic chemicals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lead exposure remains highly prevalent worldwide despite decades of research highlighting its link to numerous adverse health outcomes. In addition to well-documented effects on cognition, there is ...growing evidence of an association with antisocial behavior, including aggression, conduct problems, and crime. An updated systematic review on this topic, incorporating study evaluation and a developmental perspective on the outcome, can advance the state of the science on lead and inform global policy interventions to reduce exposure.
We aim to evaluate the link between lead exposure and antisocial behavior. This association will be investigated via a systematic review of human epidemiological and experimental nonhuman mammalian studies.
The systematic review protocol presented in this publication is informed by recommendations for the conduct of systematic reviews in toxicology and environmental health research (COSTER) and follows the study evaluation approach put forth by the U.S. EPA Integrated Risk Information System (IRIS) program.
We will search the following electronic databases for relevant literature: PubMed, BIOSIS and Web of Science. Search results will be stored in EPA’s Health and Environmental Research Online (HERO) database.
Eligible human epidemiological studies will include those evaluating any population exposed to lead at any lifestage via ingestion or inhalation exposure and considering an outcome of antisocial behavior based on any of the following criteria: psychiatric diagnoses (e.g., oppositional defiant disorder (ODD), conduct disorder (CD), disruptive behavior disorders (DBD)); violation of social norms (e.g., delinquency, criminality); and aggression. Eligible experimental animal studies will include those evaluating nonhuman mammalian studies exposed to lead via ingestion, inhalation, or injection exposure during any lifestage. The following outcomes will be considered relevant: aggression; antisocial behavior; and altered fear, anxiety, and stress response.
Screening will be conducted with assistance from an artificial intelligence application. Two independent reviewers for each data stream (human, animal) will screen studies with highest predicted relevance against pre-specified inclusion criteria at the title/abstract and full-text level. Study evaluation will be conducted using methods adapted from the U.S. EPA IRIS program. After data extraction, we will conduct a narrative review and quantitative meta-analysis on the human epidemiological studies as well as a narrative review of the experimental animal studies. We will evaluate the strength of each evidence stream separately and then will develop a summary evidence integration statement based on inference across evidence streams.
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