Investigating the Influence of Birth Month on the Incidence of Burning Mouth Syndrome

Burning mouth syndrome (BMS) is a chronic oral pain condition characterized by an uncomfortable burning sensation. While the etiology remains unknown, potential underlying pathological factors include neurological components, central sensitization, and psychiatric components. (Russo et al. 2022) The pain associated with BMS is proposed to be classified into nociceptive pain, neuropathic pain, and nociplastic pain, with a recent renewed focus on nociceptive pain, particularly in basic research. (Shinoda et al. 2022). Seasonal variations in birth month might shed light on the development of diseases. A consistent finding in schizophrenia research is that individuals born in the winter and spring months are approximately 10% more likely to develop schizophrenia compared to those born at other times of the year. (Torrey et al. 1997) An association has been found between birth seasonality and the prevalence of various diseases. (Boland et al. 2015; Shaw et al. 2014) In particular, birth month has been linked to the incidence of a range of mental illnesses, including schizophrenia and bipolar disorder. (Viejo-Romero et al. 2024; Coury et al. 2023; Robinson et al. 2023) The association between mental disorders and BMS has already been pointed out. (Kim et al. 2020) On the other hand, despite the paucity of studies investigating the association between birth month and chronic pain conditions such as BMS, a study has shown a correlation between birth month and the prevalence of various rheumatic diseases, particularly fibromyalgia which shares nociceptive pain mechanisms with BMS. (Lee et al. 2020; Gerdle et al. 2024). If there is a link between birth month and nociceptive pain, several factors could explain it. First, seasonal variations in environmental exposure may play a role. Exposure to specific environmental factors during prenatal or early postnatal development could affect pain sensitivity. For instance, sunlight exposure or pollutants might influence the formation of pain pathways. Second, seasonal fluctuations in maternal health could be involved. Maternal health during pregnancy and early infancy can impact nervous system development, potentially affecting pain sensitivity. (Colvin, McGuire, and Fowlie 2004; Marques et al. 2013) Lastly, genetic factors might also be at play, with birth month correlating with certain genetic variations that influence sensitivity to pain (Kadalayil et al. 2023). To the best of our knowledge, there are no previous studies on the seasonality of birth in patients with BMS. A retrospective chart review was performed by including consecutive patients with BMS. All patients had been referred to the Psychosomatic Dentistry Clinic in Tokyo Medical and Dental University Dental Hospital, Tokyo, Japan, between April 2018 and March 2024. Written informed consent was obtained from all participants. Patients met the criteria of BMS according to the International Classification of Headache Disorders-3. Births were classified by month similar to other studies. We studied differences in the seasonal distribution of births between the BMS patients and the Japanese general population. The monthly distribution of births in the general population was obtained from the official statistics data by the Japanese Ministry of Health, Labor, and Welfare. Statistical analysis was conducted using the chi-squared test along with the Walter–Elwood seasonality test (Walter and Elwood 1975). p value less than 0.05 was considered statistically significant. One thousand seventy patients (906 females and 106 males) were studied. The average age was 62.9 ± 13.6 years (Female 63.3 ± 13.4 years, Male 60.4 ± 14.2 years). Figures 1 and 2 show the seasonal pattern in births of patients with BMS compared to that in the general population. Despite statistical tests revealed no significant difference (total: female: male, p-value = 0.23, 0.22, 0.63 in the chi-squared test, p value = 0.50, 0.58, 0.67 in the Walter–Elwood seasonality test), there was an increase of births in female patients with BMS in January, and a decrease in May. A strength of this study lies in its large sample size. However, in our sample, we found no evidence of a season of birth bias in the risk of developing BMS. Many potential factors can explain seasonality. One factor is low prenatal vitamin D due to low sunlight exposure in the winter. Prior research has indicated a potential correlation between vitamin D deficiency and BMS; however, the study is about the patient's blood data, not about the fetal period. (Morr Verenzuela et al. 2017) While caution is warranted in interpreting these studies and our findings, the increased prevalence of patients with BMS born in January may suggest a correlation with reduced vitamin D levels during the fetal period. An expanded discussion on vitamin D highlights its role in brain development and neurotransmitter synthesis. Notably, vitamin D deficiency impacts brain neurotransmitter systems, including dopamine, which are linked to pain regulation. (Eyles 2021) This suggests biological mechanisms connecting prenatal deficiencies to later BMS manifestation. Another factor is seasonal infection during the prenatal period, such as viruses, some agents which are more prevalent in some months or seasons, resulting in differences in individual vulnerability, fetus's brain development during the perinatal period. (Yates and Mulkey 2024) Other prior researches have indicated a relationship between the season of birth and variations in brain size. (Viejo-Romero et al. 2024; Schaub et al. 2022; Torigoe et al. 2024) In light of our research findings and previous studies, BMS might be caused not by developmental or morphological problems in the brain but by functional issues. (Nagamine 2024) A research suggested that morphological changes related to chronic pain are plastic in nature and are unlikely to be congenital. (Rodriguez-Raecke et al. 2013) Comparing diseases linked to seasonal birth months with BMS, the higher average age of onset of BMS could lend further support to this hypothesis. More research is needed to fully understand this complex relationship. For example, it might be useful to conduct longitudinal studies with comprehensive pre- and perinatal data, particularly including data related to vitamin D as discussed in our study (e.g., maternal blood vitamin D levels), potentially enabling the identification of specific risk factors or use different statistical analyses to control for confounding factors. This study has notable limitations, including reliance on retrospective data, unaccounted sociodemographic and environmental confounders, lack of a control group, and insufficient prenatal and perinatal data to analyze specific risk factors. The lack of correlation between birth month and BMS may imply that, unlike certain mental health disorders, the etiology of BMS may not be influenced by seasonal factors in the same way. However, the observed slight increase in births in January and decrease in May among patients with BMS warrants further investigation, as it may suggest subtle environmental influences that have yet to be understood. Takayuki Suga: writing – original draft, data curation. Chihiro Takao: data curation, writing – review and editing, investigation. Takahiko Nagamine: supervision, writing – review and editing. Akira Toyofuku: conceptualization, supervision, methodology, funding acquisition. The study received approval from the Ethical Committee of Tokyo Medical and Dental University Dental Hospital (approval number: D2013-005-04). Written informed consent was obtained from all participants. The authors declare no conflicts of interest. The datasets generated and/or analyzed during this study are available from the corresponding author upon reasonable request.