No seasonality in the risk of multiple sclerosis in an equatorial country: A case-control ecological study.

BACKGROUND: Multiple sclerosis risk has been shown to have seasonal variations that are more pronounced in higher latitudes. However, this phenomenon has not been adequately studied near the Equator. OBJECTIVE: To explore the risk of multiple sclerosis associated with month, season of birth, and sunlight exposure variables in Colombia. METHODS: In this case-control study, 668 multiple sclerosis cases were matched to 2672 controls by sex and age. Association of multiple sclerosis with each month/season of birth and sunlight exposure variables was estimated with multilevel mixed-effects logistic regression and ecological regression models, respectively. Seasonality in the births of multiple sclerosis was assessed with a non-parametric seasonality test. RESULTS: We found a higher probability of multiple sclerosis in September (0.25; 95% confidence interval (CI) = 0.21-0.31) and lower in March (0.15; 95% CI = 0.10-0.18), which turned non-significant after a multiple comparisons test. Sunlight exposure variables had no significant effect on the risk of MS, and the tests of seasonality in the births of MS did not show significant results. CONCLUSION: Our results show no seasonality in the risk of multiple sclerosis near the Equator, supporting the hypothesis that this phenomenon is latitude dependent.

Does month of birth influence colorectal cancer prognosis?

PURPOSE: The main aim of this study was to identify a possible association between month of birth of colorectal cancer (CRC) patients and overall survival (OS) or disease-free survival (DFS). METHODS: This observational study included all consecutive adult patients diagnosed with CRC undergoing oncological surgery from January 2005 to December 2019 with a minimum follow-up of 10 years. The outcome variables were locoregional recurrence, death due to cancer progression, OS and DFS. Non-supervised learning techniques (K-means) were conducted to identify groups of months with similar oncologic outcomes. Finally, OS and DFS were analysed using Kaplan-Meier and Cox regression tests. The model was calibrated with resampling techniques and subsequently a cross-validation was performed. RESULTS: A total of 2520 patients were included. Three birth month groups with different oncologic outcomes were obtained. Survival analysis showed between-group differences in OS (p < 0.001) and DFS (p = 0.03). The multivariable Cox proportional hazards model identified the clusters obtained as independent prognostic factors for OS (p < 0.001) and DFS (p = 0.031). CONCLUSION: There is an association between month of birth and oncologic outcomes of CRC. Patients born in the months of January, February, June, July, October and December had better OS and DFS than those born in different months of the year.

Month of birth and mental disorders: A population-based study and validation using global meta-analysis.

OBJECTIVE: Month of birth (MOB) is associated with specified mental disorders (MDs). However, whether these relationships extend to all MDs remains unclear. We investigate the association using a population-based cohort study and a meta-analysis. METHODS: First, we examined patients with 34 DSM-5-classified MDs in the Taiwan national database. We estimated the relative risk ratios (RR) of each illness in each MOB relative to that in the general population and assessed the periodicity, with six further sensitivity analyses. Second, we searched PubMed, Embase, and Cochrane for related articles through 31 December 2020. We used a random-effects model, pooled RRs with 95% confidence intervals of each MOB from the identified studies, and transformed them from MOB to relative age in a year or season. RESULTS: The cohort included 1,951,777 patients. Except for posttraumatic stress disorder, dissociative disorders, feeding/eating disorders, gender dysphoria, and paraphilic disorders, the other MDs had significant MOB periodicity. The meta-analysis included 51 studies investigating 10 MDs. The youngest age at the start of school owing to MOB was associated with the highest RRs of intellectual disability (1.13), autism (1.05), attention-deficit/hyperactivity disorder (1.13). Winter births had significant risks of schizophrenia (1.04), bipolar I disorder (1.02), and major depressive disorder (1.01), and autumn births had a significant risk of alcohol use disorder (1.02). No significant associations between season of birth and Alzheimer's disease, or eating disorders were found. CONCLUSIONS: MOB is related to the risks of certain MDs. This finding provides a reference for future research on the etiology of MDs.

Month-of-birth-effect in multiple sclerosis in Austria.

BACKGROUND: The month-of-birth-effect (MoBE) describes the finding that multiple sclerosis (MS) patients seem to have been born significantly more frequently in spring, with a rise in May, and significantly less often in autumn and winter with the fewest births in November. OBJECTIVES: To analyse if the MoBE can also be found in the Austrian MS population, and if so, whether the pattern is similar to the reported pattern in Canada, United Kingdom, and some Scandinavian countries. METHODS: The data of 7886 MS patients in Austria were compared to all live births in Austria from 1940 to 2010, that is, 7.256545 data entries of the Austrian birth registry and analysed in detail. RESULTS: Patterns observed in our MS cohort were not different from patterns in the general population, even when stratifying for gender. However, the noticeable and partly significant ups and downs over the examined years did not follow the distinct specific pattern with highest birth rates in spring and lowest birth rates in autumn that has been described previously for countries above the 49th latitude. CONCLUSION: After correcting for month-of-birth patterns in the general Austrian population, there is no evidence for the previously described MoBE in Austrian MS patients.

Effect of the month of birth on the height of young adult males.

OBJECTIVE: To explore a possible association between the month of birth and the final adult height in men and see if this could be described in terms of periodicity. MATERIALS AND METHODS: We used anthropometric data of 15,109 young male conscripts of the Greek Army. The data were collected from May 2006 until May 2010 and included men who had been born over a period of 12 years (1980-1991). The data were grouped in 12 monthly periods and analyzed with the use of a sinusoidal model. RESULTS: There was a statistically significant month-of-birth effect on height variation, which was described by a sinusoidal model with period T = 12 months, amplitude 0.223 cm and, two extremes which corresponded to the end of April/beginning of May (peak) and to the end of October/beginning of November (nadir). DISCUSSION: Our results corroborate previous findings suggesting a seasonality in human height without, however, being able to provide a definitive explanation for this phenomenon.

Modeling month-season of birth as a risk factor in mouse models of chronic disease: from multiple sclerosis to autoimmune encephalomyelitis.

Month-season of birth (M-SOB) is a risk factor in multiple chronic diseases, including multiple sclerosis (MS), where the lowest and greatest risk of developing MS coincide with the lowest and highest birth rates, respectively. To determine whether M-SOB effects in such chronic diseases as MS can be experimentally modeled, we examined the effect of M-SOB on susceptibility of C57BL/6J mice to experimental autoimmune encephalomyelitis (EAE). As in MS, mice that were born during the M-SOB with the lowest birth rate were less susceptible to EAE than mice born during the M-SOB with the highest birth rate. We also show that the M-SOB effect on EAE susceptibility is associated with differential production of multiple cytokines/chemokines by neuroantigen-specific T cells that are known to play a role in EAE pathogenesis. Taken together, these results support the existence of an M-SOB effect that may reflect seasonally dependent developmental differences in adaptive immune responses to self-antigens independent of external stimuli, including exposure to sunlight and vitamin D. Moreover, our documentation of an M-SOB effect on EAE susceptibility in mice allows for modeling and detailed analysis of mechanisms that underlie the M-SOB effect in not only MS but in numerous other diseases in which M-SOB impacts susceptibility.-Reynolds, J. D., Case, L. K., Krementsov, D. N., Raza, A., Bartiss, R., Teuscher, C. Modeling month-season of birth as a risk factor in mouse models of chronic disease: from multiple sclerosis to autoimmune encephalomyelitis.

Influence of the relative age effect on children's scores obtained from the Canadian assessment of physical literacy.

BACKGROUND: Age grouping by the imposition of a cut-off date, common in sports and education, promotes a relative age difference that is associated with developmental advantages for children who are born on the "early side" of the cut-off date and disadvantages to those born later in the same year, which is known as the relative age effect (RAE) bias. Acquiring an adequate level of physical literacy is important for children to remain active for life. The Canadian Assessment of Physical Literacy (CAPL) is an assessment protocol that encompasses measures in the domains of children's Daily Behaviours, Physical Competence, Motivation and Confidence, and Knowledge and Understanding. The purpose of this study was to ascertain whether the CAPL scores were susceptible to the RAE, which could affect our interpretation of the CAPL findings. METHODS: This cross-sectional study examined if scores obtained in the CAPL (i.e., the four domains individually and the total CAPL score) were susceptible to the RAE in children aged 8 to 12 years and, if so, which physical competence assessments (movement skills, cardiorespiratory, strength, muscular endurance, flexibility, and body composition measurements) were more susceptible. Participants (n = 8233, 49.8% boys) from the Royal Bank of Canada-CAPL Learn to Play project from 11 sites in seven Canadian provinces were tested using the CAPL protocol. RESULTS: Among boys and girls, the RAE was significantly associated with two and three of the four domain scores, respectively, after controlling for covariates. However, effect sizes were negligible for the comparisons between quarters of the year and physical literacy domains and overall scores. For the main effect of the relative age, boys and girls born in the first three months of the year were taller (F(3, 4074) = 57.0, p < 0.001, ƒ2 = 0.04 and F(3, 4107) = 58.4, p < 0.001, ƒ2 = 0.04, respectively) and demonstrated greater muscular strength (F(3, 4037) = 29.2, p < 0.001, ƒ2 = 0.02 and F(3, 4077) = 25.1, p < 0.001, ƒ2 = 0.02, respectively) compared with those born later in the same year. CONCLUSIONS: Collectively, our results suggest that the RAE bias is mainly negligible with regard to the domain scores and overall CAPL scores in this large sample of children.

Seasonality and autoimmune diseases: The contribution of the four seasons to the mosaic of autoimmunity.

Autoimmune diseases (ADs) are a heterogeneous groups of diseases that occur as a results of loss of tolerance to self antigens. While the etiopathogeneis remain obscure, different environmental factors were suggested to have a role in the development of autoimmunity, including infections, low vitamin D levels, UV radiation, and melatonin. Interestingly, such factors possess seasonal variation patterns that could influence disease development, severity and progression. Vitamin D levels which reach a nadir during late winter and early spring is correlated with increased disease activity, clinical severity as well as relapse rates in several disease entities including multiple sclerosis (MS), non-cutaneous flares of systemic lupus erythematosus (SLE), psoriasis, and rheumatoid arthritis (RA). Additionally, immunomodulatory actions of melatonin secretion ameliorate the severity of several ADs including MS and SLE. Melatonin levels are lowest during spring, a finding that correlates with the highest exacerbation rates of MS. Further, melatonin is postulated to be involved in the etiopathogenesis of inflammatory bowel diseases (IBD) through it influence on adhesion molecule and therefore transcription factor expression. Moreover, infections can mount to ADs through pro-inflammatory cytokine release and human antigen mimicry. Seasonal patterns of infectious diseases are correlated with the onset and exacerbation of ADs. During the winter, increased incidence of Epstein-Barr virus (EBV) infectious are associated with MS and SLE flares/onset respectively. In addition, higher Rotavirus infections during the winter precedes type 1 diabetes mellitus onset (T1DM). Moreover, Escherichia coli (E. coli) infection prior to primary biliary cirrhosis (PBC) and T1DM disease onset subsequent to Coxachievirus infections are seen to occur during late summer, a finding that correlate with infectious agents' pattern of seasonality. In this review, the effects of seasonality on the onset, relapses and activity of various ADs were discussed. Consideration of seasonal variation patterns of ADs can possibly provide clues to diseases pathogenesis and lead to development of new approaches in treatment and preventative care.

Association between seasonal factors and multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system. MS is causing progressive and relapsing neurological disability, due to demyelination and axonal damage. The etiopathogenesis of MS is poorly understood. A number of environmental factors have been previously suggested, including: month of birth, vitamin D levels, smoking and viral infections. Previous studies assessing seasonal variation of relapses in multiple sclerosis have had conflicting results. The aim of this review is to assess the association between seasonal factors and MS, in terms of disease onset, relapses and activity.

Seasonality of birth patterns in an Australian cohort of patients with biopsy-confirmed idiopathic inflammatory myopathy.

Environmental exposures in the foetal period may predispose to autoimmunity. Aim of this study is to investigate whether seasonality in birth patterns exists in idiopathic inflammatory myopathies (IIM). We used Stata (StataCorp USA, version 13.0) and the user-written routine command 'circsummarise' to assess birth seasonality among South Australian patients with histologically confirmed IIM subsequent to 1980 using their date of birth. There was no evidence for a seasonal birth pattern among IIM patients overall (n = 568), however there were some ethnic variances in birth patterns among non-Caucasian patients. There was evidence for birth seasonality among both Aboriginal (mean = 7 July, Rayleigh P = 0.04) and Asian patients (mean = 12 August, Rayleigh P-value = 0.038). Non-Caucasians born in the third quarter of the calendar year may have an increased risk of developing IIM. Large international studies of IIM patients of diverse ethnicity are required to clarify the role of perinatal exposures in disease susceptibility.

Month of birth and risk of multiple sclerosis in Kuwait: a population-based registry study.

BACKGROUND: Multiple sclerosis (MS) is a complex immune-mediated disorder of central nervous system with undefined etiology. This study examined the month of birth effect on subsequent MS risk later in the life in Kuwait. METHODS: The month of birth of MS patients enrolled in Kuwait MS Registry between 1 January 1950-30 April 2013 was compared with the month of births in the general population during the comparable period. Multivariable log-linear Poisson regression model was used to analyze the data. RESULTS: Data on 1035 confirmed MS patients were collected, of which 65.2% were female and 77.1% were Kuwaiti. The overall risk of MS births (per 10(5) births in general population) was 28.5 (95% confidence interval (CI): 26.8-30.3). Multivariable log-linear Poisson regression model showed a significant (p=0.004) peak in the number of MS births during December (θo=340(o)). During this month, the risk of MS birth was 1.3 times the risk of MS birth in the trough month after adjusting for the effects of gender and nationality (adjusted relative risk=1.3; 95% CI: 1.1-1.6). The amplitude (α±standard deviation: 0.13±0.014) of sinusoidal curve showed a significant (p=0.004) difference of 13% from the mean to maximum MS births during peak month. CONCLUSIONS: This study showed a statistically significant month of birth effect on MS risk with 13% excess MS births during December in Kuwait. Future studies may contemplate ascertaining the seasonal factors eliciting the observed association. The insight gained by unraveling such factors may help curtail MS risk in this and other similar settings in the region.

Seasonality and clinical characteristics of MS in an equatorial country.

BACKGROUND: Month and season of birth have been associated with risk of multiple sclerosis (MS), but there is relatively little evidence regarding their influence on the timing and severity of disease at onset. OBJECTIVE: To assess whether month and season of birth influence the age and phenotype at onset of MS as well as its severity in a cohort of Colombian patients. METHODS: This study is an analysis on MS cases only, drawn from a previously published case-control study. MS cases confirmed with current diagnostic criteria cared for at least once in our center were included. We assessed the influence of the month and season of birth in the age at MS onset, MS severity score, and age-related MS severity score using multiple and pairwise comparisons. Age at onset was also studied using Kaplan-Meier survival estimates compared with the log-rank test. The likelihood of progressive MS onset was evaluated with OR estimated from logistic regression models adjusted for age at onset and sex. RESULTS: 668 MS cases were included. No significant differences were found in the age at MS onset according to month of birth or season of birth. Neither month of birth nor season of birth conferred significant differences in MS severity score or age-related MS severity score. No significant association was found between month (ORs ranging from 0.62 to 3.11, none significant) or season of birth (OR 0.91; 95 %CI: 0.46-1.84) with primary progressive MS. CONCLUSION: The month or season of birth do not appear to influence the age onset and phenotype of MS in our country.

Month of birth as a latitude-dependent risk factor for multiple sclerosis in Norway.

OBJECTIVE: We aimed to determine if the risk of Multiple Sclerosis (MS) is associated with month of birth in Norway and to explore a possible latitudinal gradient. METHODS: All patients with MS born between 1930 and 1979 registered in the Norwegian MS Registry or ascertained in Norwegian prevalence studies were included (n = 6649). The latitude gradient was divided in Southern, Middle and Northern Norway, according to the estimated regional yearly mean vitamin D effective UV dose. RESULTS: Risk of MS was 11% higher for those born in April (p = 0.045), and 5% higher for those born in May (p = 0.229), 5% lower for those born in November (p = 0.302) and 12% lower for those born in February (p = 0.053) compared with the corresponding population, unaffected mothers and siblings. In Southern Norway the odds ratio of MS births in April and May was 1.05 (0.98-1.24), in Middle Norway 1.11 (0.97-1.27) and in Northern Norway 1.28 (1.0-1.63) compared with the other months. CONCLUSIONS: This study confirms previous reports of increased MS births in spring and decreased MS births in the winter months. This could support the role of decreased sunlight exposure during pregnancy and vitamin D deficiency in prenatal life in MS.

Seasonality of main childhood embryonal tumours and rhabdomyosarcoma, France, 2000-2015.

Few studies have investigated the seasonal patterns of embryonal tumours. Based on data from the French National Registry of Childhood Cancers, the present study aimed to investigate seasonal variations in embryonal tumour incidence rates by month of birth and by month of diagnosis. The study included 6635 primary embryonal tumour cases diagnosed before the age of 15 years over the period 2000-2015 in mainland France. Assuming monthly variations in incidence rates were homogeneous over 2000-2015, we used a Poisson regression model to test for overall heterogeneity in standardised incidence ratios (SIRs) by month of birth or diagnosis. The seasonal scan statistic method was used to detect monthly excesses or deficits of embryonal tumour cases over the whole study period. The annual reproducibility of the observed monthly variations was formally tested. An overall heterogeneity in incidence rates by month of birth was observed for rhabdomyosarcoma in boys only. Based on the month of diagnosis, a seasonality was evidenced for unilateral retinoblastoma, with a lower incidence rate in the summer (SIRJul-Aug  = 0.68, 95% CI = 0.52-0.87), whilst the incidence rate of rhabdomyosarcoma tended to be lower in August (SIRAug  = 0.68, 95% CI = 0.52-0.89). No seasonality was detected for the other embryonal tumour groups by month of birth or month of diagnosis. This study is one of the largest to have investigated the seasonality of childhood embryonal tumours. The study showed a seasonal variation in the incidence rates by month of diagnosis for unilateral retinoblastoma and rhabdomyosarcoma. Our findings are likely to reflect a delay in consultation during the summer months. However, the role of seasonally varying environmental exposures cannot be ruled out.

Triggering multiple sclerosis at conception and early gestation: The variation in ultraviolet radiation is as important as its intensity.

Background and objectives: Medical science needs to further elucidate the role of ultraviolet radiation (UVR), geographic latitude, and the role of vitamin D in the autoimmune disease multiple sclerosis (MS). We separated several papers into categories out of the thousands published and used their conclusions to explore the relationship between UVR and MS. Relevance: MS is increasing in incidence, particularly in women where MS is two to three times that in men and particularly severe in African Americans. Methods: We collected UVR data at our observatory in Central Maine and calculated the average coefficient of variation (CVUVR) for each month for 15 years (2007-2021, inclusive). Results: The month of conception (MOC) is more important than the month of birth (MOB) in explaining how UVR triggers the variable genetic predisposition to MS. We hypothesize that the rapidly increasing CVUVR is important in preventing an increase in the activity of the vitamin D receptor (VDR) from August to December, which then requires a higher intensity of UVR later in life to suppress the immune system, therefore predisposing to more MS. Limitations: One observatory at about 44° latitude. Conclusions: While variation in UVR is important at the MOC if UVR exceeds a threshold (e.g., if the sunspot number equals or is greater than 90, usually at a solar cycle MAX, or at elevations above approximately 3,000 feet above sea level), the MS mitigating vitamin D-VDR mechanism is overwhelmed and the genotoxic effects of higher-intensity UVR promote MS in those with a genetic predisposition. What is new in this research: This paper offers a new concept in MS research.

Month-of-Birth Effect on Muscle Mass and Strength in Community-Dwelling Older Women: The French EPIDOS Cohort.

Background. Vitamin D is involved in muscle health and function. This relationship may start from the earliest stages of life during pregnancy when fetal vitamin D relies on maternal vitamin D stores and sun exposure. Our objective was to determine whether there was an effect of the month of birth (MoB) on muscle mass and strength in older adults. Methods. Data from 7598 community-dwelling women aged ≥ 70 years from the French multicentric EPIDOS cohort were used in this analysis. The quadricipital strength was defined as the mean value of 3 consecutive tests of the maximal isometric voluntary contraction strength of the dominant lower limb. The muscle mass was defined as the total appendicular skeletal muscle mass measured using dual energy X-ray absorptiometry scanner. The MoB was used as a periodic function in regressions models adjusted for potential confounders including age, year of birth, latitude of recruitment center, season of testing, body mass index, number of comorbidities, IADL score, regular physical activity, sun exposure at midday, dietary protein intake, dietary vitamin D intake, use vitamin D supplements, history and current use of corticosteroids. Results. A total of 7133 older women had a measure of muscle strength (mean age, 80.5 ± 3.8 years; mean strength, 162.3 ± 52.1 N). Data on total ASM were available from 1321 women recruited in Toulouse, France (mean, 14.86 ± 2.04 kg). Both the sine and cosine functions of MoB were associated with the mean quadricipital strength (respectively ß = -2.1, p = 0.045 and ß = -0.5, p = 0.025). The sine function of MoB was associated with total ASM (ß = -0.2, p = 0.013), but not the cosine function (ß = 0.1, p = 0.092). Both the highest value of average quadricipital strength (mean, 163.4 ± 20.2 N) and the highest value of total ASM (15.24 ± 1.27 kg) were found among participants born in August. Conclusions. Summer-early fall months of birth were associated with higher muscle mass and strength in community-dwelling older women.

Month of birth and the risk of narcolepsy: a systematic review and meta-analysis.

STUDY OBJECTIVES: The aim of this study is to evaluate the relationship between the month of birth (MOB) and the risk of narcolepsy. METHODS: We conducted a systematic review of the electronic databases PubMed, Embase, and Cochrane CENTRAL from their inception to September 30, 2021. We also added data on narcolepsy from the National Health Insurance Research Database in Taiwan. Then we extracted the relative risk (RR) ratios of narcolepsy in each month of birth to those of the general population and transformed them from MOB to season. A random-effects model was used to calculate pooled RR ratios from the meta-analysis and 95% confidence interval (CI). RESULTS: The meta-analysis analyzed 7 studies and included 3,776 patients from 8 areas (Canada, China, France, Germany, Hong Kong, Netherlands, Taiwan, and United States). The RR ratio was highest in March (1.11; 95% CI, 0.99-1.26) and August (1.11; 95% CI, 0.98-1.26) and lowest in April (0.90; 95% CI, 0.78-1.03). However, none of the MOBs reached statistical significance. Moreover, the narcolepsy risk patterns on the 3 continents (Asia, Europe, and North America) were different. In North America, the highest and lowest significant risks were found in March (1.47; 95% CI, 1.20-1.79) and September (0.75; 95% CI, 0.56-0.99). In Asia, the lowest notable risk was in April (0.80; 95% CI, 0.66-0.97). In Europe, the risk of narcolepsy was not significantly related to any MOB. In terms of seasons, only spring MOBs in North America had a significantly higher risk (1.21; 95% CI, 1.06-1.38). CONCLUSIONS: The findings indicated that the risk of narcolepsy and MOB differed across the 3 continents. This study indicates the important role of environmental factors in narcolepsy. SYSTEMATIC REVIEW REGISTRATION: Registry: PROSPERO; Identifier: CRD42020186660. CITATION: Hsu C-W, Tseng P-T, Tu Y-K, et al. Month of birth and the risk of narcolepsy: a systematic review and meta-analysis. J Clin Sleep Med. 2022;18(4):1113-1120.

The effect of ultraviolet radiation on the incidence and severity of major mental illness using birth month, birth year, and sunspot data.

Background and objectives: The evaluation of the severity of patients afflicted with major mental illness (MMI) has been problematic because of confounding variables and genetic variability. There have been multiple studies that suggest several human diseases, especially schizophrenia, are predisposed to be born in certain months or seasons. This observation implied an epigenetic effect of sunlight, likely ultraviolet radiation (UVR), which is damaging to DNA, especially in an embryo. This paper outlines a method to evaluate the severity of schizophrenia (SZ), bipolar disorder (BPD), and schizoaffective disorder (SZ-AFF) using the month/year of birth of those affected compared to the month/year of birth of the general population (GP). Relevance: Our previous research found that more intense UVR (equal to or greater than 90 sunspot number (SSN)) had a negative effect on the average human lifespan. Also, human birth rates vary in frequency by month of birth reflecting variables like availability of food, sunlight, and other unknown epigenetic factors. We wanted to see if the patient month of birth varied from the average birth months of the general population and if UVR has an epigenetic effect promoting these diseases. Methods: We obtained the month and year of birth of 1,233 patients admitted over a 15-year period to Maine's largest state psychiatric hospital and counted the months of birth for each diagnosis of SZ, BPD, and SZ-AFF, and compared these results to the general population's birth months of 4,265,555 persons from U. S. Census Year 2006. The number of patients in each month was normalized to August and compared with the normalized birth months of the general population (GP). Plots of the normalized months were considered rates of change (e.g., derivatives) and their respective integrals gave domains of each mental illness relative to the GP. Normalizing the GP to unity was then related to the factor 1.28, e.g., 28% more entropy, deduced from the Sun's fractal dimension imprinted on biological organisms. Results: The percent of patients meeting our criterion for severity: SZ = 27%; BPD = 26%; SZ-AFF = 100%. Conclusions: High UVR intensity or a rapid increase in UVR in early gestation are likely epigenetic triggers of major mental illness. BPD is more epigenetically affected than SZ or SZ-AFF disorders. We found that 52% of 1,233 patients comprised the core function of a tertiary-care psychiatric hospital. Also, mental illness exacerbated when the median SSN doubled. This work also validates the Kraeplinian dichotomy. What is new in this research: This paper offers a new paradigm for evaluating the severity of MMI and supports significant epigenetic effects from UVR.

Seasonality of month of birth in patients with autoimmune endocrine diseases: A systematic review.

BACKGROUND: Exposure to seasonal environmental factors during gestation or early in the postnatal period could influence the development of autoimmunity, determining a seasonality in the month of birth (MOB). There are studies evaluating this potential seasonality in patients with type 1 diabetes (T1D), autoimmune thyroid diseases (AITD), and Addison's disease (ADD), but results have been controversial. METHODS: Systematic review according to PRISMA guidelines, using PubMed, Web of Science and WorldCat databases (2005-2020) of studies that explored the association between the seasonality of the MOB and T1D, AITD and ADD. Information on sex and age, location, methodology and internal quality, seasonal patterns, hypotheses and other factors proposed to explain seasonality were extracted. Differences in season and month of birth were further discussed. RESULTS: The initial search retrieved 300 articles, and after further screening, 11 articles fulfilled inclusion criteria and were finally selected and reviewed. 73% found a seasonal pattern and 64% showed birth peaks in spring and/or summer. Hashimoto's thyroiditis and women exhibited a higher seasonality. Ultraviolet radiation, Vitamin D levels and viral infections were identified as influencing factors. CONCLUSIONS: The effect of certain seasonal factors during foetal development, reflected by the seasonal differences in the MOB, could contribute to the development of endocrine autoimmune diseases in predisposed patients. Further research is needed to elucidate the mechanisms underlying the observed seasonality.

Impact of the Season of Birth on the Development of Juvenile Idiopathic Arthritis in the United States: A Nationwide Registry-based Study.

OBJECTIVE: Autoimmune disorders result from the interplay of genetic and environmental factors. Many autoimmune disorders are associated with specific seasons of birth, implicating a role for environmental determinants in their etiopathology. We investigated if there is an association between the season of birth and the development of juvenile idiopathic arthritis (JIA). METHODS: Birth data from 10,913 children with JIA enrolled at 62 Childhood Arthritis and Rheumatology Research Alliance Registry sites was compared with 109,066,226 US births from the same period using a chi-square goodness-of-fit test. Season of birth of the JIA cohort was compared to the US population estimate using a 2-sided 1-sample test for a binomial proportion and corrected for multiple comparisons. Secondary analysis was performed for JIA categories, age of onset, and month of birth. RESULTS: A greater proportion of children with JIA were born in winter (January-March) compared to the US general population (25.72% vs 24.08%; corrected P < 0.0001). This observation was also true after stratifying for age of onset (≤ or > 6 yrs). When analyzed by the month of birth, a greater proportion of children with JIA were born in January compared to the US population (9.44% vs 8.13%; corrected P < 0.0001). CONCLUSION: Relative to the general population, children with JIA are more often born in the winter, and specifically in the month of January. These observations support the hypothesis that seasonal variations in exposures during the gestational and/or early postnatal periods may contribute to development of JIA.