The prevalence of autism spectrum disorder has risen in recent decades. Given the growing evidence that prenatal fluoride exposure may be neurotoxic, we examined associations between prenatal fluoride exposure and parent-reported autistic behaviors in preschool-aged children. We studied 453 mother-child pairs using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, a prospective Canadian birth cohort. Autistic behaviors were assessed in children at 3 to 4 years using the Social Responsiveness Scale-Second Edition (SRS-2) Preschool Form, where a higher score indicates more autistic behaviors. We estimated prenatal fluoride exposure using three methods: (i) maternal urinary fluoride adjusted for specific gravity (MUFSG), from spot urine samples collected at each trimester and the mean calculated across samples, (ii) daily maternal fluoride intake, based on self-reported consumption of tap water, coffee, and tea during the first and third trimesters, and (iii) water fluoride concentration in tap water. We used multivariable linear regression models to estimate associations between the SRS-2 scale T-scores and each fluoride exposure separately. We used multivariable logistic regression to estimate the association between each prenatal fluoride exposure and an elevated SRS-2 total T-score (i.e., 90th percentile or higher). Potential effect modification of MUFSG was examined by child sex, daily folic acid supplementation, and plasma total folate in pregnancy. The mean SRS-2 total T-score for children aged 3 to 4 years was 45.3 (SD = 6.1, range = 34 to 85). The median MUFSG concentration was 0.43 mg/L (interquartile range = 0.33 mg/L). MUFSG was not significantly associated with the SRS-2 total T-score in multivariable linear regression (β = -0.16; 95

BACKGROUND AND AIM: A growing body of evidence indicates that prenatal exposure to fluoride is neurotoxic to child development. However, epidemiologic research examining fluoride's effect on autism spectrum disorder (ASD) is lacking. Our aim was to examine the association of prenatal fluoride exposure with ASD-like behaviors in a sample of preschool aged children living in regions with fluoridated and non-fluoridated community water. METHODS: We analyzed 502 mother-child pairs from the Maternal-Infant Research on Environmental Chemicals (MIREC), a prospective multicentered Canadian birth cohort, with available data on prenatal fluoride exposure, ASD-like behaviors, and covariates. We measured fluoride exposure by averaging maternal urinary fluoride adjusted for specific gravity (MUFsg) across three trimesters. We assessed children's ASD-like behaviors at 3-4 years of age using the parent-reported Social Responsiveness Scale-2 (SRS-2) Preschool Form, with higher scores indicating more behavioral symptomology. Covariate adjusted linear and quantile regression models were used to estimate the difference in the relationship between MUFsg and SRS-2 conditional mean and quantile subscale T-scores, respectively. We adjusted all regression models for baseline maternal age, second-hand smoke, marital status, parity, child sex, study site, and the HOME score that was assessed at child follow-up visit. RESULTS:Mean MUFsg concentration was 0.53 mg/L (SD=0.38), and mean SRS-2 Total T-score was 45.3 (SD=6.2). In multiple linear regression, a 1 mg/L increase in MUFsg concentration was not statistically associated with SRS-2 Total T-score (β=0.12; 95% CI, -1.36, 1.60; P=0.87). Likewise, we observed no statistical association for all other SRS-2 subscale T-scores. In quantile regression, there was no statistical association between MUFsg and SRS-2 Total T-score across percentiles: 0.1, 0.3, 0.5, 0.7 and 0.9. Effect modification by sex was not observed. CONCLUSIONS:In this Canadian cohort, we found no evidence of a statistical association between prenatal fluoride exposure and ASD-like behaviors among preschool aged children. KEYWORDS: biomarkers of exposure, children's environmental health, epidemiology, fluoride, neurodevelopmental outcomes

Background: There is growing recognition that preconception health, defined as the health of all reproductive-age individuals, impacts reproductive and perinatal outcomes. Although women with disabilities are becoming pregnant at increasing rates, little is known about their preconception health. Our objective was to describe the preconception health characteristics of women with physical, sensory, and intellectual/developmental disabilities and compare these characteristics with women without disabilities. Materials and Methods: We conducted a population-based cross-sectional study of 15- to 44-year-old women with physical (n = 253,184), sensory (n = 93,170), intellectual/developmental (n = 8,986), and multiple disabilities (n = 29,868), and women without these disabilities (n = 2,307,822) using Ontario health administrative data (2017-2018). We described preconception health variables related to social determinants of health, physical health status, psychosocial well-being, history of assault, medication use, and continuity of primary care and compared women with and without disabilities in crude and age-standardized analyses, with standardized differences >0.10 indicating clinically meaningful results. Results: Women with physical, sensory, intellectual/developmental, and multiple disabilities had poorer preconception health than women without disabilities. Disparities were pronounced for physical health status, psychosocial well-being, use of potentially teratogenic medications, and history of assault. Of all groups, women with intellectual/developmental disabilities had the greatest disparities. Conclusion: Further research is needed to identify contributors to poor preconception health among women with disabilities and to develop tailored preconception health interventions to meet their unique needs and experiences.

CONTEXT:Women with disabilities are at elevated risk for pregnancy, delivery, and postpartum complications. However, there has not been a synthesis of literature on the neonatal and infant health outcomes of their offspring.OBJECTIVE:We examined the association between maternal disability and risk for adverse neonatal and infant health outcomes.DATA SOURCES:Cumulative Index to Nursing and Allied Health Literature, Embase, Medline, and PsycINFO were searched from database inception to January 2020.STUDY SELECTION:Studies were included if they reported original data on the association between maternal physical, sensory, or intellectual and/or developmental disabilities and neonatal or infant health outcomes; had a referent group of women with no disabilities; were peer-reviewed journal articles or theses; and were written in English.DATA EXTRACTION:We used standardized instruments to extract data and assess study quality. DerSimonian and Laird random effects models were used for pooled analyses.RESULTS:Thirty-one studies, representing 20 distinct cohorts, met our inclusion criteria. Meta-analyses revealed that newborns of women with physical, sensory, and intellectual and/or developmental disabilities were at elevated risk for low birth weight and preterm birth, with smaller numbers of studies revealing elevated risk for other adverse neonatal and infant outcomes.LIMITATIONS:Most studies had moderate (n = 9) or weak quality (n = 17), with lack of control for confounding a common limitation.CONCLUSIONS:In future work, researchers should explore the roles of tailored preconception and perinatal care, along with family-centered pediatric care particularly in the newborn period, in mitigating adverse outcomes among offspring of women with disabilities.

Background: Women with disabilities experience significant health disparities. A barrier to progress in addressing these disparities is the lack of population-based data on their health outcomes, which are needed to plan health care delivery systems. Administrative health data are increasingly being used to measure the health of entire populations, but these data may only capture impairment and not activity and participation restrictions. Objective: We conducted a systematic review to identify and appraise existing literature on the development and validation of algorithms to identify reproductive-aged women with physical and sensory disabilities in administrative health data. Methods: We searched Medline, EMBASE, CINAHL, PsycINFO, and Scopus from inception to April 2019 for studies of the development and/or validation of algorithms using diagnostic, procedural, or prescription codes to identify physical and sensory disabilities in administrative health data. Study and algorithm characteristics were extracted and quality was assessed using standardized instruments. Results: Of 14,073 articles initially identified, we reviewed 6 articles representing 2 unique algorithms. One algorithm aimed to correlate diagnoses, procedure codes, and prescriptions with ability to access routine care as an indicator of functional limitation. The other algorithm used diagnostic and procedure codes to identify use of mobility-assistive devices to measure functional limitation. Only one algorithm was validated against self-reported disability. Conclusions: Our findings underscore the need to strengthen current methods to identify disability in administrative health data, including linkage with other sources of information on functional limitations, so that population-based data can be used to optimize health care for women with disabilities. (c) 2020 Elsevier Inc. All rights reserved.

One in 10 reproductive-aged women has a physical, sensory, or intellectual/developmental disability.1Statistics Canada Disability in Canada: initial findings from the Canadian Survey on Disability. Statistics Canada, Ottawa2016Google Scholar The prevailing assumptions are that these women are not sexually active or are unlikely to experience pregnancy because of their medical risk.2Silver M.G. Eugenics and compulsory sterilization laws: providing redress for the victims of a shameful era in United States history.Geo Wash L Rev. 2003; 72: 862Google Scholar We compared the rates of a recognized pregnancy among women with and without disabilities. This population-based, repeated, cross-sectional study was completed in Ontario, Canada. Health administrative data sets, covering the whole population, were linked using a unique encoded identifier and accessed and analyzed at ICES. Included were women aged 15–44 years who had an identified physical, sensory, or intellectual/developmental disability, based on ≥2 physician visits or ≥1 emergency department visits or hospitalizations between database inception and study entry.3Darney B.G. Biel F.M. Quigley B.P. Caughey A.B. Horner-Johnson W. Primary caesarean delivery patterns among women with physical, sensory, or intellectual disabilities.Womens Health Issues. 2017; 27: 336344Abstract Full Text Full Text PDF Scopus (51) Google Scholar,4Lin E. Balogh R. Cobigo V. Ouellette-Kuntz H. Wilton A. Lunsky Y. Using administrative health data to identify individuals with intellectual and developmental disabilities: a comparison of algorithms.J Intellect Disabil Res. 2013; 57: 462-477Crossref PubMed Scopus (83) Google Scholar Rates of recognized pregnancy (any live birth, pregnancy loss, or induced abortion) were calculated per 1000 women in fiscal year 2017/2018 for each disability group overall and by 5 year age groups and then compared by Poisson regression to women without any documented disability. Changes in rates between 2003/2004 and 2017/2018 were also assessed by Poisson regression, with a year*disability status interaction term. Time trends were plotted using 3 year moving averages. Data use was authorized under section 45 of Ontario’s Personal Health Information Protection Act. In 2017/2018, there were 253,661 15-44 year old women with a physical, 91,695 with a sensory, 8919 with an intellectual/developmental, and 29,515 with ≥2 (multiple) disabilities and 2,335,019 women without disabilities. Compared with women without disabilities, overall recognized pregnancy rates were slightly lower in those with physical or sensory disabilities and much lower in women with intellectual/developmental or multiple disabilities (Figure 1). Adolescent pregnancy rates were highest in women with intellectual/developmental disabilities and also higher in women with physical and sensory disabilities, each compared with women without disabilities (Figure 1). Between 2003/2004 and 2017/2018, pregnancy rates decreased slightly in women without disabilities and appeared stable among those with physical or intellectual/developmental disabilities. However, pregnancy rates rose significantly in women with sensory or multiple disabilities (year*disability status interaction term P < .0001) (Figure 2). Of all pregnancies, the proportion in women with any disability increased from 8.5% in 2003/2004 to 13.0% in 2017/2018. In additional analyses, there were lower rates of pregnancies ending in live birth or induced abortion per 1000 women in each disability group vs women without disabilities. However, rates of pregnancy loss were slightly, although nonsignificantly, elevated in women with physical (risk ratio, 1.04, 95% confidence interval, 1.00–1.09) or sensory disabilities (risk ratio, 1.06, 95% confidence interval, 0.99–1.13) compared with nondisabled women. Our findings counter assumptions that pregnancy rarely occurs in women with disabilities.2Silver M.G. Eugenics and compulsory sterilization laws: providing redress for the victims of a shameful era in United States history.Geo Wash L Rev. 2003; 72: 862Google Scholar Higher pregnancy rates in adolescents with (vs without) disabilities are concerning and may speak to the need for better access to sexual health education and contraception. Women with disabilities have reported barriers accessing reproductive health care services, including providers who are reluctant to discuss their reproductive health, physically inaccessible care settings, and lack of tailored information.5Malouf R. Henderson J. Redshaw M. Access and quality of maternity care for disabled women during pregnancy, birth and the postnatal period in England: data from a national survey.BMJ Open. 2017; 20e016757Google Scholar Given that 1 in 8 pregnancies herein was among women with a disability, greater attention to the reproductive and perinatal health care needs of women with disabilities is warranted.

OBJECTIVE:There are unexplained sex-specific changes in the clinical expression of ankylosing spondylitis (AS). We sought to examine the potential effect of exogenous estrogen in the form of oral contraceptive pills (OCP) on AS initiation and severity.METHODS:This cross-sectional study consisted of women with AS from the membership of the Spondylitis Association of America. Measures of disease severity included use of biological agents and hip replacement surgery, while Bath AS Functional Index (BASFI) scores served as a surrogate marker of disability. Information was obtained using a patient questionnaire on patient demographics, OCP use, pregnancy history, AS duration, medication use, and hip replacement.RESULTS:There were 571 women with AS who participated in our study, consisting of 448 OCP ever-users and 123 non-OCP users. The mean age of OCP users was 42.7 yrs (± 11.5) and of non-OCP users, 48.4 yrs (± 12.1). No difference was noted in the age at initial onset of back pain. However, OCP users were significantly younger at the time of diagnosis of AS (36.5 yrs vs 39.1 yrs, p = 0.02). There were no significant differences between the 2 groups in tumor necrosis factor inhibitor or opioid use, BASFI scores, pregnancy complications, or hip surgery.CONCLUSION:The use of exogenous estrogens in the form of OCP is not associated with a measurable effect on initiation or severity of AS. Biologic and social factors may contribute to earlier diagnosis of AS in OCP users. This is the largest study to date investigating the potential effect of exogenous estrogens in women with AS.

Objective. To identify soluble biomarkers associated with response to therapy with tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA). Methods. The study was conducted at a PsA clinic where patients are assessed every 6 months, and serum samples are collected and stored once a year at the time of clinical assessment. Forty patients with active PsA who gave serum samples prior to treatment with TNFi and after at least 3 months of therapy were identified. Patients were classified as TNFi responders if tender joint count was < 3, swollen joint count was 0, and Psoriasis Area and Severity Index score was < 4 at the time the second sample was collected. The following biomarkers were tested by ELISA: TNF superfamily 14, matrix metalloprotease-3 (MMP-3), receptor activator of nuclear factor kappa-B ligand, osteoprotegerin, cartilage oligomeric matrix protein (COMP), CPII, C2C and C1-2C, CS-846, and highly sensitive C-reactive protein. Paired t tests and logistic regression was used for statistical analyses. Results. After a mean treatment duration of 11 months with TNFi (etanercept 28 patients, adalimumab 6, golimumab 4, infliximab 2), 29 patients were classified as TNFi responders. Baseline level of MMP-3 was independently associated with responder status (OR 1.067 for each 1-unit increase, p = 0.045). A reduction in MMP-3 levels with therapy increased the odds of achieving response (OR 1.213 for each 1-unit change, p = 0.030), whereas a reduction in COMP decreased the odds (OR 0.587, for each 100-unit increase, p = 0.039). None of the other biomarkers was associated with response. Conclusion. Baseline as well as reduction in serum MMP-3 and increase in serum COMP are independently associated with response to TNFi therapy in patients with PsA.

OBJECTIVE:To investigate the features of ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA) in a Canadian cohort of 639 patients with AS and 73 patients with nr-axSpA.METHODS:Clinical and laboratory data were compared for patients with AS and nr-axSpA enrolled in a longitudinal SpA cohort.RESULTS:The proportion of male patients was higher in AS than in nr-axSpA (76.2% vs 47.9%; p < 0.0001). There was no difference in the presence of HLA-B27 between AS (78.9%) and nr-axSpA (72.5%) patients, nor in age at the time of diagnosis, although AS patients were younger at the time of symptom onset (23.9 yrs vs 26.4 yrs; p = 0.03). Disease duration at the time of last clinic visit was longer for AS than for nr-axSpA patients (17.7 yrs vs 12.1 yrs; p = 0.0002). Acute-phase reactants were higher in AS than in nr-axSpA (C-reactive protein 11.4 vs 5.2, p < 0.0001; erythrocyte sedimentation rate 13.7 vs 9.9, p = 0.02). The Bath Ankylosing Spondylitis Metrology Index was higher in patients with AS (2.84 vs 1.35, p < 0.0001).CONCLUSION:Patients with nr-axSpA were more likely to be female and to have lower inflammatory markers than patients with AS. When restricted to female patients only, acute-phase reactants did not differ significantly between AS and nr-axSpA. The evidence provides indirect support for the concept that nr-axSpA may represent an early form of AS, but that also has features of a distinct disease entity with significant burden of symptoms.

Objective. There is an unacceptable delay in the diagnosis of axial spondyloarthritis (axSpA) in its early stages among patients at high risk, in particular those with inflammatory bowel disease (IBD). Our objectives were to develop a sensible and reliable questionnaire to identify undetected axSpA among patients with IBD. Methods. Literature was reviewed for item generation in the Toronto axSpA Questionnaire on IBD (TASQ-IBD). Sensibility of the questionnaire was assessed among healthcare professionals and patients. This assessment was related to purpose and framework (clinical function, clinical justification, and clinical applicability), face validity, comprehensiveness [oligo-variability (limiting the questionnaire to important items) and transparency], replicability, content validity, and feasibility. The test-retest reliability study was administered to 77 patients with established IBD and axSpA. Kappa agreement coefficients and absolute agreement were calculated for items. Results. Three domains included IBD, inflammatory back symptoms, and extraaxial features. The entry criterion required a patient to have IBD and back pain or stiffness that ever persisted for ≥ 3 months. Iterative sensibility assessment involved 16 items and a diagram of the back. Kappa coefficients ranged from 0.81–1.00 for each item. Absolute agreement across all items ranged from 91% to 100%. Conclusion. TASQ-IBD is a newly developed, sensible, and reliable case-finding questionnaire to be administered to patients with IBD who have ever had chronic back pain or stiffness persisting for ≥ 3 months. It should facilitate identification and timely referral of patients with IBD to rheumatologists and minimize the delay in diagnosis of axSpA. Consequently, it should assess the prevalence of axSpA in IBD.

Background: There is an unacceptable delay in diagnosis of axial Spondyloarthritis (axSpA) especially in its early stages among patients with inflammatory bowel disease (IBD). Objective: to develop a sensible and reliable questionnaire to identify undetected axSpA among

Objective.To determine the association between urolithiasis and syndesmophyte formation and the effect of urolithiasis on ankylosing spondylitis (AS) disease activity.Methods.In a longitudinal cohort of 504 patients with AS, we conducted an analysis of all patients with AS who have a history of urolithiasis. All patients met the modified New York criteria for AS. Demographics, clinical characteristics, extraarticular features, and comorbidities are systematically recorded in the database. We compared disease activity, functional indices, medical therapy and radiographic damage between AS patients with (Uro+) and without urolithiasis (Uro–) using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS).Results.Thirty-eight patients with AS (7.5%) had a history of urolithiasis in our cohort. Seventy-six patients with AS who did not have urolithiasis, matched for age, sex, and ethnicity, were selected as controls. Patients who were Uro+ were more likely to have more functional disability, based on the Bath AS Functional Index (BASFI; mean 5.3 vs 3.6 in control group, p = 0.003). Trends were noted in the Uro+ group toward higher Bath AS Disease Activity Index (BASDAI; mean 4.9 vs 4.0, p = 0.09), more peripheral joint involvement (p = 0.075), and higher frequency of biologic therapy (p = 0.09). No significant difference was detected in mSASSS or the Bath AS Metrology Index (BASMI). Significant association with diabetes mellitus (DM; p = 0.016) and Crohn’s disease (p = 0.006) was noted in the Uro+ group.Conclusion.Although there is no acceleration of syndesmophyte formation or spinal mobility restriction, more functional disability was detected in the urolithiasis group. The higher risk with concomitant DM or Crohn’s disease should alert clinicians to these comorbidities in Uro+ patients with AS.

Objective.To evaluate the effect of pregnancy on ankylosing spondylitis (AS).Methods.Our study aimed to determine the severity of back pain and stiffness pre-, during, and postpartum in patients with AS and controls, and corresponding extraarticular symptoms.Results.Nineteen female patients with AS (35 pregnancies) and 33 controls (77 pregnancies) were studied. Improvement in pain was reported in 51% of AS patients, predominantly in the first trimester, with significant improvement in pain than stiffness. In both groups, pain worsened in later stages, likely secondary to biomechanical loading. Postpartum pain scores in AS returned to prepartum levels in general.Conclusion.Pregnancy does not substantially aggravate disease activity or severity in AS.