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Gender-specific inflammatory burden and headache risk in youth: a NHANES analysis

Head & Face Medicine volume 20, Article number: 71 (2024) Cite this article

Abstract

Background

Headaches are a common and often debilitating condition among youth. The Inflammatory Burden Index (IBI), a simple surrogate marker of systemic inflammation, has been linked to various diseases. However, evidence for its relationship with headaches, particularly in youth, is lacking. This study aimed to investigate the association between IBI and persistent headache in youth, with a focus on evaluating gender-specific responses to IBI exposure.

Methods

We analyzed data from 2,210 young people in the 2001–2004 National Health and Nutrition Examination Survey (NHANES). The association between IBI and frequent or severe headaches in the past year was investigated using weighted logistic regression models. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated, and threshold effect analyses were performed.

Results

Youths in the highest IBI quartile (Q4) had a 46% higher risk of severe headaches compared to the lowest quartile (Q1) (OR: 1.46, 95% CI: 1.12–1.91, P = 0.0051). Gender-stratified analysis revealed a significant association between high IBI and headache risk in females (OR: 1.48; 95% CI: 1.03–2.11, P = 0.0324), but not in males. Threshold effect analysis identified an IBI breakpoint of 3.78, below which the headache risk increased significantly in females under 18 years (OR: 1.12, 95% CI: 1.01–1.25, P = 0.0385).

Conclusions

Our findings demonstrate a significant association between elevated IBI and increased headache risk in youth, particularly in females. This gender-specific effect suggests that inflammatory processes may play a more prominent role in headache pathophysiology among female youth. These results underscore the importance of considering inflammatory markers in the early identification and prevention of youth headaches, especially in females.

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Introduction

Headaches are a common and often disabling condition among youth. According to the latest Global Burden of Disease Study, among people aged 15–39 years, the prevalence of migraine has increased from 11.2% in 1990 to 14.1% in 2019, while the prevalence of tension headache has increased from 23.2% in 1990 to 26.3% in 2019 [1]. The prevalence of headache is particularly high among youth (12–20 years), ranging from 50 to 79.5% [2, 3]. Tension-type headaches and migraines are particularly prevalent, impacting academic performance, social interactions, and overall quality of life [4, 5]. This trend highlights the growing health problem of headache in the young population. Early-life exposure to inflammation during this critical developmental period may have lasting effects on headache susceptibility [6, 7]. Recent studies suggest that inflammatory processes can sensitize pain pathways and alter neurotransmitter systems [8, 9], potentially increasing vulnerability to headaches both acutely and later in life. Despite their widespread occurrence, the underlying mechanisms of headaches in youth remain incompletely understood, presenting a significant challenge for effective prevention and treatment strategies.

In recent years, mounting evidence has implicated inflammation as a key player in headache pathophysiology [10, 11]. Inflammatory processes have been shown to sensitize pain pathways, alter neurotransmitter systems, and disrupt the blood-brain barrier, all of which may contribute to headache development and persistence [12, 13]. The concept of an “inflammatory burden” - a cumulative measure of systemic inflammation - has emerged as a potentially valuable tool for assessing an individual’s overall inflammatory status and its relationship to various health outcomes.

While the link between inflammation and headaches has been explored in adult populations [14], there is a paucity of research examining this relationship specifically in youth. Moreover, gender differences in headache prevalence and characteristics are well-documented [15, 16], with females generally reporting higher rates of headaches, particularly migraines. Recent studies have revealed significant sex-based disparities in clinical presentation, treatment responses, and lifestyle factors affecting headache disorders. Ahmad highlighted that women experience more frequent and severe migraine attacks, with notably different trigger patterns and comorbidity profiles compared to men [16]. These differences may be attributed to both biological factors (hormonal influences, particularly estrogen fluctuations) and sociocultural aspects affecting symptom reporting and healthcare-seeking behaviors. Additionally, Fourier et al. demonstrated that even in traditionally male-predominant conditions like cluster headache, women exhibit distinct clinical features and treatment responses, suggesting fundamental sex-based differences in pain processing and inflammatory responses [17]. However, it remains unclear whether the impact of inflammatory burden on headache risk differs between male and female youths, representing a critical gap in our understanding of headache pathophysiology during this developmental period.

The Inflammatory Burden Index (IBI) is a composite measure that serves as a surrogate marker for systemic inflammation. It is calculated using the formula: ln(CRP × neutrophil / lymphocyte), where CRP is C-reactive protein. This index combines multiple inflammatory markers to provide a more comprehensive assessment of an individual’s overall inflammatory status [18].

The IBI has gained attention in recent years due to its ability to capture a broader picture of inflammatory processes compared to individual markers alone. It has been associated with various diseases and conditions, including cardiovascular diseases [19], bone disorders [20], and certain cancers [18]. For instance, a recent study has shown a significant association between IBI and all-cause mortality in patients with osteoarthritis. Xie et al. (2023) found that higher IBI was associated with an increased risk of all-cause mortality (OR = 1.23, 95% CI: 1.14–1.33) in individuals with osteoarthritis [20].

The utility of IBI lies in its potential to reflect both acute and chronic inflammatory states, making it a valuable tool for assessing overall inflammatory burden [18]. Its components - CRP, neutrophils, and lymphocytes - each play distinct roles in the inflammatory process, and their combination in the IBI formula provides a more nuanced view of systemic inflammation.

Given the growing recognition of inflammation as a key factor in various pathological processes, including pain disorders, the IBI represents a promising metric for investigating the relationship between systemic inflammation and conditions such as headaches in youth.

To address these knowledge gaps, we conducted a gender-specific analysis using data from the National Health and Nutrition Examination Survey (NHANES) database. The primary objectives of this study were to:

  1. 1.

    Investigate the association between the Inflammatory Burden Index (IBI) and the risk of frequent or severe headaches in youth aged 12–20 years, using data from the National Health and Nutrition Examination Survey (NHANES).

  2. 2.

    Examine potential gender differences in the relationship between IBI and headache risk, with a particular focus on identifying any disparities between male and female youth.

  3. 3.

    Explore potential threshold effects of IBI on headache risk, particularly in female youth.

By elucidating the role of inflammation in youth headaches and exploring gender-specific patterns, this study aims to contribute to a more nuanced understanding of headache pathophysiology in this age group. Such insights could inform the development of targeted prevention strategies and personalized treatment approaches, ultimately improving the management of headaches in youth populations.

Materials and methods

Study design and population

The design of the study and the individuals involved were carefully selected through the NHANES program, which employs a sophisticated and intricate methodology to choose a representative sample of the U.S. population biennially. The primary objective is to evaluate and assess the health and nutritional status of individuals in the United States. In order to uphold ethical standards, the survey underwent approval from the Institutional Review Board established by the National Center for Health Statistics. Additionally, all participants provided informed written consent voluntarily before being included in the study. The NHANES study gathers a diverse array of data, encompassing demographic details, responses to questionnaires, medical examination results, and laboratory findings.

During the NHANES 2001–2004 cycle, a total of 21,092 individuals partook in the research initiative. Following the exclusion of subjects lacking information on the IBI record and severe headache diagnosis data from the past 12 months, the remaining sample was utilized for analytical purposes (Fig. 1). Our study focused on a cohort of young adults aged 12–20 years, including adolescence (12–17 years) and young adults (18–20 years). This choice of age range allowed us to comprehensively analyze the period of transition within the youth period.

Fig. 1
figure 1

Flow chart of the study participants

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Data collection and measures

In this study, the primary exposure variable was the Inflammatory burden index. The IBI was calculated according to the formula ln (CRP× neutrophil mg/dL / lymphocyte mg/dL) [21], The main outcomes were severe headache in the past 12 months. Headache was diagnosed if the participant answered “yes” to the inquiry “During the past 12 months, have you/has SP had ***frequent or severe headaches, including migraines?”. To investigate whether the IBI is associated with the risk of headache.

The participants all furnished data regarding their age, gender, ethnicity (categorized as Mexican American, other Hispanic, non-Hispanic White, non-Hispanic Black, or another group), educational attainment (categorized as below high school, high school graduate or equivalent, or beyond high school), family poverty-to-income ratio (PIR) through completion of survey questionnaires. The calculation of body mass index (BMI) involved dividing weight (kg) by height (m2) [22]. Analysis of laboratory findings was conducted on serum samples collected during the patients’ visits to the mobile examination unit, with the vials maintained under suitable frozen conditions until transfer to the National Center for Environmental Health for analysis.

Statistical analysis

Descriptive statistics

Baseline characteristics were stratified into two categories based on the methodology utilized: one category distinguished by the presence or absence of severe headache, while the other category was based on quartiles of the IBI index. As for the age, it was categorized into three groups: <12 years, 12–18 years, and > 18 years for analysis using Empower stats software. Continuous variables were denoted as mean ± standard deviation (SD) and were subjected to comparison through t-tests or Wilcoxon rank-sum tests, as deemed suitable. Categorical variables were represented as counts (weighted proportions) and were contrasted via Pearson chi-square test.

Regression models

The relationship between IBI and headache was computed through weighted univariate and multiple logistic regression analyses, with results presented as odds ratios (OR) and 95% confidence intervals (CI). Accordingly, we identified four nodes positioned at the default 5%, 35%, 65%, and 95% fixed percentiles of the IBI index distribution. To address potential confounding factors, we implemented three weighted logistic regression and weighted regression models: model 1, without adjustments; model 2, adjusted for age, sex; and model 3, adjusted for age, sex, and body mass index. The selection of covariates in our models was based on meticulously chosen variables with established associations to outcomes supported by existing scientific literature.

In the present investigation, “WTSAF2YR” (representing the sample weighting code for the fasting subsample from 2001 to 2004) was employed as a weighting factor. Additional details regarding the survey sample design and weighting methodologies can be found at https://wwwn.cdc.gov/nchs/nhanes/analyticguidelines.aspx.

Threshold effect analysis

We conducted a threshold effect analysis using a piecewise linear regression model to identify potential breakpoints in the relationship between IBI and headache risk, particularly focusing on gender-specific effects.

Sensitivity analyses

To assess the robustness of our findings, we conducted sensitivity analyses by excluding extreme values of IBI (defined as values beyond 1.5 times the interquartile range). We then repeated our main analyses to compare results with and without these extreme values.

A two-tailed p < 0.05 was considered to indicate statistical significance. The data underwent analysis using the statistical software packages R (The R Foundation; http://www.r-project.org; version 3.6.3) and Empower Stats (www.empowerstats.net, X&Y solutions, Inc. Boston, Massachusetts).

Results

Participant characteristics

A total of 2211 participants (1094 males and 1117 females) were recruited for the current investigation. The fundamental attributes of the individuals experiencing acute headache compared to those who were not, are presented in Table 1. Roughly 26.6% (588) of the individuals within our research cohort reported severe headache. More specifically, among those with severe headache, a higher percentage of females and Non-Hispanic Black, individuals exhibited a reduced family poverty income ratio (PIR), an elevated body mass index (BMI), decreased levels of alkaline phosphatase, hemoglobin, and glucose. Furthermore, individuals experiencing frequent or severe headaches demonstrated a higher IBI Q4, increased total cholesterol and LDL levels, and decreased albumin concentrations. The baseline characteristics of all participants and those with or without headache categorized by the IBI are depicted in Additional file 1: Tables S1.

Table 1 Baseline characteristics of participants with or without severe headache
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Univariate analysis: demographic and inflammatory predictors of severe headache

In this study, we analyzed the association between various demographic, clinical, and inflammatory factors with headache risk in youth, stratified by gender. The hazard ratio for age indicated no significant difference in headache risk between participants under and over 18 years of age (OR: 1.00, 95% CI: 0.80–1.25, P = 0.9896). However, gender-specific analysis revealed that females had a significantly higher risk of headaches compared to males (OR: 1.45, 95% CI: 1.20–1.75, P = 0.0001, see Table 2).

Race also emerged as a significant factor, with Other Hispanic and Non-Hispanic Black youth showing an increased headache risk compared to Mexican Americans (OR: 1.72, 95% CI: 1.11–2.68, P = 0.0161 and HR: 1.35, 95% CI: 1.07–1.71, P = 0.013, respectively, see Table S2). Body mass index (BMI) was positively correlated with headache risk (OR: 1.03, 95% CI: 1.01–1.05, P = 0.0002), while the poverty income ratio (PIR) was inversely associated with the risk (OR: 0.91, 95% CI: 0.86–0.97, P = 0.0059). Inflammatory markers such as C-reactive protein (CRP), neutrophils, lymphocytes, and white blood cells (WBC) showed no significant association with headache risk.

Finally, the Inflammatory Burden Index (IBI) demonstrated a dose-response relationship, with youth in the highest quartile (Q4) having a significantly higher risk of headaches compared to those in the lowest quartile (Q1) (OR: 1.46, 95% CI: 1.12–1.91, P = 0.0051). Other biochemical parameters such as lactate dehydrogenase (LDH), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) did not show significant associations with headache risk.

Table 2 Univariate analysis of severe headache
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Multivariable regression analysis of inflammatory burden and headache risk

In multivariate regression analyses, when IBI was divided into quartiles, the risk of headache in the highest quartile group (Q4) was significantly higher than in the lowest quartile group (Q1) in all models. The model 1 showed a 46% increased risk of headache in the Q4 group (OR: 1.46, 95% CI: 1.12–1.91, P = 0.0051). In the model2, the Q4 group had a 43% increased risk of headache (OR: 1.43, 95% CI: 1.09–1.88, P = 0.0106), and in the model3, the risk increased to 38% (OR: 1.38, 95% CI: 1.16–2.07, P = 0.0196).

In analyses with quartiles as continuous variables, for each quartile increase in IBI, the risk of model2 (OR: 1.10, 95% CI: 1.01–1.20, P = 0.0325), and significantly more in the model3 (OR: 1.03, 95% CI: 1.01–1.14, P = 0.0582). These results suggest that a higher inflammatory burden index is associated with an increased risk of headache in youth, particularly significant in the interquartile analyses (see Table 3).

Table 3 ORs (95% CIs) for frequent/significant headache according to the IBI
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Stratified analysis

In the stratified analysis, we evaluated the association between various demographic, clinical, and inflammatory variables with headache risk in female patients, while categorizing the data into relevant subgroups.

Age stratification revealed that youth under 18 years of age had a moderately increased risk of headaches (OR: 1.36, 95% CI: 1.00–1.85, P = 0.0486), while those aged 18 and above had an even higher risk (OR: 1.97, 95% CI: 1.02–3.81, P = 0.0433). Gender analysis showed a significant association between female gender and headache risk (OR: 1.48, 95% CI: 1.03–2.11, P = 0.0324), whereas the association was not significant in males (OR: 1.33, 95% CI: 0.88–2.00, P = 0.1734). (See Table S2).

We further did stratified analysis on female group falling within IBI Q4, since IBI.Q4 was found to be the most significant across all the models mentioned above (see Table 4 and Table S3). We found several parameters are of great significance, for Age: Significant association with pain in females under 18 (OR 1.55, 95% CI: 1.02–2.37, P = 0.0414), but not in those 18 and older (OR 1.15, 95% CI: 0.31–4.34, P = 0.8349).For Glucose Levels: Higher pain risk in the 86–329 mg/dl group (OR 2.32, 95% CI: 1.25–4.33, P = 0.0079).For HDL Levels: Increased pain risk in the highest HDL group (1.45–2.97 mmol/L) (OR 1.99, 95% CI: 1.05–3.79, P = 0.0359). For WBC Count: Significant association with pain in the 6.2–7.9 × 10^9/L group (OR 3.45, 95% CI: 1.74–6.82, P = 0.0004).

PIR: Higher income-to-poverty ratio associated with increased pain risk (OR 2.11, 95% CI: 1.13–3.95, P = 0.0198).For Race: Significant association with pain in Non-Hispanic White females (OR 2.01, 95% CI: 1.04–3.86, P = 0.0374).

Table 4 Stratified analysis for female falling within IBI.Q4
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Threshold effect analysis in females

In the analysis of the threshold effect of the Inflammatory Burden Index (IBI) on headache risk in females, we examined the data across different age groups and identified a potential threshold (K) at which the association between IBI and headache risk might change.

In Model I, no significant interaction was observed between age and IBI (P-interaction: 0.880), and the overall effect of IBI across all ages was not significant (OR: 1.00, 95% CI: 0.99–1.01, P = 0.8032).

Model II introduced a threshold effect analysis with a breakpoint (K) identified at an IBI value of 3.78. For females under 18 years of age, IBI values below the threshold were associated with a significantly increased risk of headaches (OR: 1.12, 95% CI: 1.01–1.25, P = 0.0385). However, this association was not significant for IBI values above the threshold (OR: 1.00, 95% CI: 0.98–1.01, P = 0.4875). The difference in effects between the two segments was statistically significant (OR: 0.89, 95% CI: 0.79–0.99, P = 0.0386).

For females aged 18 years and older, the threshold effect was less clear, with no significant associations observed in either segment of the threshold (OR: 1.99, 95% CI: 0.39–10.23, P = 0.4096 for IBI < K and OR: 1.00, 95% CI: 0.98–1.01, P = 0.6730 for IBI > K, see Table 5).

The overall difference in effects across all ages was significant, suggesting that the risk of headaches associated with IBI may be more pronounced at lower IBI values, particularly in younger females. The log-likelihood ratio test further confirmed the significance of this threshold effect (P = 0.042).

The analysis supports the idea that there may be a specific IBI range in which the risk of headaches is heightened, especially in younger females, indicating the importance of early detection and intervention in this group.

Table 5 Threshold effect analysis in females
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Sensitivity analyses results

After excluding extreme IBI values, consistent results is observed with our primary analyses, suggesting that our findings are robust to potential outliers. The association between IBI and headache risk remained significant in females (adjusted OR: 1.48, 95% CI: 1.03–2.11, p = 0.0324), while no significant association was observed in males.

Discussion

Our study reveals a significant association between the Inflammatory Burden Index and headache risk in youth, with particularly strong evidence for gender-specific effects. The stronger correlation observed in female youth suggests inflammation plays a more prominent role in headache pathophysiology for this group, aligning with previous research demonstrating higher prevalence and severity of headaches in females [23, 24].

A novel and clinically significant finding is the threshold effect identified in younger females (under 18 years), with an IBI breakpoint at 3.78. This non-linear relationship reveals that IBI values below 3.78 show a significant positive association with headache risk (OR: 1.12, 95% CI: 1.01–1.25, P = 0.0385), while this association weakens above the threshold. This finding has important clinical implications for early intervention and personalized risk assessment. Even relatively low levels of inflammatory burden appear associated with increased headache risk, suggesting potential benefits of early anti-inflammatory interventions. Furthermore, this threshold could serve as a clinical marker for identifying young females who might benefit from more intensive headache prevention strategies. The magnitude of this gender-specific association (OR: 1.48 in females) warrants particular attention from a clinical perspective. This 48% increase in headache risk associated with elevated IBI represents a clinically meaningful difference that could inform risk assessment and prevention strategies. For context, this effect size is comparable to other established risk factors for youth headache, such as family history and stress levels [25]. The clinical utility of this finding is enhanced by the fact that IBI can be readily measured through routine blood tests, potentially offering an objective tool for risk stratification in young female patients. This could help clinicians identify high-risk individuals who might benefit from more intensive preventive measures before the onset of severe or chronic headache patterns.

The gender-specific effect observed in our study aligns with existing literature on sexual dimorphism in pain perception and inflammatory responses. Onan et al. reported higher prevalence of both tension-type headaches and migraines in females [26], suggesting common underlying mechanisms across headache subtypes. This consistent gender disparity appears to be driven by multiple biological factors: estrogen’s modulation of pain sensitivity and inflammatory responses [27]. sex-specific differences in microglial activation patterns leading to enhanced female neuroinflammatory responses [28], and differential expression of specific microRNAs associated with migraine pathophysiology [29]. Several factors identified in our univariate analysis may contribute to elevated IBI in youth. Higher BMI and cholesterol levels showed association with increased inflammatory burden [30, 31], potentially through adipose tissue’s release of pro-inflammatory cytokines and oxidative stress-induced endothelial dysfunction [32]. Recent research by Huang et al. identified potential drug targets related to lipid metabolism for migraine treatment [31], supporting the role of metabolic factors in headache pathophysiology. Additionally, the interaction between poor glycemic control and chronic inflammation [33] may explain the higher IBI values observed in our pain-apparent group.

These findings highlight the potential value of comprehensive treatment approaches, particularly for female youth. Lifestyle modifications targeting BMI, cholesterol, and glucose levels through balanced diet and regular physical activity may help manage inflammatory burden and reduce headache risk. However, translating these findings into effective treatments remains challenging, especially in pediatric populations where many preventive medications have shown limited efficacy compared to placebo [34]. The identification of an IBI threshold suggests that inflammatory markers could potentially serve as objective indicators for treatment initiation and monitoring, particularly in female youth where the relationship between inflammation and headache risk appears strongest.

Our analysis also revealed significant racial/ethnic differences in headache risk, with Other Hispanic and Non-Hispanic Black youth showing higher risk compared to Mexican Americans. These racial disparities may reflect complex interactions between genetic, socioeconomic, and healthcare access factors. Previous studies have documented racial differences in pain perception and treatment [35], with evidence suggesting both biological and social contributors. Genetic variations affecting pain sensitivity and inflammatory responses may differ across ethnic groups [36]. Additionally, socioeconomic factors and healthcare disparities could influence both the development and management of headaches. The higher prevalence in certain racial groups highlights the need for culturally sensitive approaches to headache prevention and treatment, as well as efforts to address underlying healthcare disparities.

Interestingly, our observation of decreased headache severity in females over 18 years suggests age-specific patterns that warrant further investigation. Rather than contradicting existing knowledge about menstrual migraines [24, 37], this finding suggests distinct headache subtypes may emerge during the youth period. Understanding these age-related variations could lead to more targeted and effective treatment strategies, considering both hormonal status and developmental stage.

Our study has several important limitations. First, the cross-sectional nature of NHANES data prevents establishing causality between IBI and headache risk - we cannot determine whether elevated inflammatory burden precedes headache development or emerges as a consequence of recurrent headaches. Second, reliance on self-reported headache data may introduce recall bias, particularly regarding frequency and severity assessments. The lack of standardized headache classification and detailed characterization (such as duration, triggers, and specific features) limits our ability to differentiate between various headache subtypes. Additionally, while we have justified our methodological choice not to include threshold effect visualizations, this analytical limitation warrants acknowledgment as it could provide additional insights into the IBI-headache relationship.

Several potential confounders, including family history, sleep quality, hormonal status, and gut-brain axis factors, were not accounted for in the NHANES dataset. Our age group categorization may oversimplify developmental stages, particularly concerning pubertal status which could influence both inflammatory markers and headache susceptibility. When we further adjusted for neutrophils, the association between IBI and headache was attenuated, suggesting that the effect of IBI might be partially mediated through neutrophil counts. However, as neutrophils are a component of IBI, including it as a covariate may lead to over-adjustment. Similar considerations led us to exclude CRP from our final adjusted models, as including components of the IBI calculation as covariates could mask true associations.

Conclusions

In conclusion, our analysis reveals a significant association between elevated Inflammatory Burden Index (IBI) and increased headache risk in female youth, particularly among those younger than 18 years of age. While dysglycemia shows a strong correlation with pain in this group, these findings suggest that chronic inflammation plays a critical role in youth headache. However, it is important to note that these results are based on a specific population and time frame, and may not be generalizable to all youth or other demographic groups.

Our study provides valuable insights into the potential role of inflammation in headache risk among youth, particularly females. However, further research is needed in several key areas: (1) Longitudinal studies to establish temporal relationships between inflammatory burden and headache progression, particularly during critical developmental periods; (2) More comprehensive assessment of headache characteristics using standardized diagnostic criteria; (3) Investigation of the interaction between inflammation, hormonal factors, and other potential contributing factors to headache risk in youth; and (4) Intervention studies to evaluate whether modifying inflammatory burden through targeted treatments affects headache outcomes.

Additionally, while our results suggest potential targets for intervention, clinical trials are necessary to determine the efficacy of anti-inflammatory strategies in preventing or managing headaches in young people. Future studies should also explore the interplay between inflammation, hormonal changes, and other potential contributing factors to headache risk in youth.

In light of these findings and limitations, we recommend that clinicians consider inflammatory markers as part of a comprehensive assessment of headache risk in young patients, particularly females, while recognizing the need for individualized approaches to diagnosis and treatment.

Data availability

Data is provided within the manuscript or supplementary information files.

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Funding

This work was supported by the third batch of the Ningbo Health Youth Technical Cadre program (QNJSGG-3-ZBB, Prof. Binbin Zhu), the key disciplines of Ningbo City (ZD2020008, Dr. Changshun Huang), and Ningbo Top Medical and Health Research Program (No.2024010317).

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Authors and Affiliations

  1. Anesthesiology Department, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, China

    Binbin Zhu, Rui Zhao, Changshun Huang, Yiwei Zhang & Yijun Chen

  2. Pain Clinic in Bund Campus, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, China

    Binbin Zhu

  3. Health Science Center, Ningbo University, Ningbo, 315211, China

    Binbin Zhu & Rui Zhao

  4. Nephrology Department, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, China

    Long Wang

  5. Department of Pain Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China

    Zhiyou Peng

Authors
  1. Binbin Zhu
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  3. Long Wang
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  4. Changshun Huang
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  5. Yiwei Zhang
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Contributions

ZBB and ZR collected the epidemiological and clinical data. WL, PZY and ZYW were responsible for statistical data. PZY and ZBB drafted the manuscript. ZBB, CYJ and HCS were responsible for funding, study conception, design, revising, and submitting the final manuscript. All authors contributed to the article and approved the submitted version.

Corresponding authors

Correspondence to Binbin Zhu, Changshun Huang or Yijun Chen.

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Ethical approval

This study utilized publicly available data from the National Health and Nutrition Examination Survey (NHANES), which is conducted by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC). The NHANES protocol was approved by the NCHS Research Ethics Review Board (ERB), and all participants provided informed consent before data collection. For participants under 18 years of age, parental permission was obtained, and child assent was collected when appropriate. As our study involved secondary analysis of de-identified, publicly available data, it was exempt from additional institutional review board approval. We adhered to the ethical guidelines for the use of NHANES data as outlined by the NCHS, including proper citation and acknowledgment of the data source. All analyses were conducted in compliance with the NHANES data use agreement, ensuring participant confidentiality and data integrity.

Consent for publication

The present study utilized data from the National Health and Nutrition Examination Survey (NHANES), which is publicly available and de-identified. As per NHANES guidelines, all participants provided informed consent for their data to be used in research and subsequent publications. No additional consent was required for this specific analysis and publication, as the data were already anonymized and intended for public use in research. The authors affirm that this manuscript is an honest, accurate, and transparent account of the study being reported, and that no important aspects of the study have been omitted.

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The authors declare no competing interests.

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Zhu, B., Zhao, R., Wang, L. et al. Gender-specific inflammatory burden and headache risk in youth: a NHANES analysis. Head Face Med 20, 71 (2024). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13005-024-00475-5

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13005-024-00475-5

Keywords

Head & Face Medicine

ISSN: 1746-160X

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