Risk factors and risk profiles for neck pain in young adults: Prospective analyses from adolescence to young adulthood-The North-Trøndelag Health Study.

The objective was to investigate risk factors and risk profiles associated with neck pain in young adults using longitudinal data from the North-Trøndelag Health Study (HUNT). Risk factors were collected from adolescents (13-19 years of age), and neck pain was measured 11 years later. The sample was divided into two: Sample I included all participants (n = 1433), and Sample II (n = 832) included only participants who reported no neck/shoulder pain in adolescence. In multiple regression analyses in Sample I, female sex (OR = 1.9, 95% CI [1.3-2.9]), low physical activity level (OR = 1.6, 95% CI [1.0-2.5]), loneliness (OR = 2.0, 95% CI [1.2-3.5]), headache/migraine (OR = 1.7, 95% CI [1.2-2.6]), back pain (OR = 1.5, 95% CI [1.0-2.4]) and neck/shoulder pain (OR = 2.0, 95% [CI 1.3-3.0]) were associated with neck pain at the 11-year follow-up. Those with a risk profile including all these risk factors had the highest probability of neck pain of 67% in girls and 50% in boys. In Sample II, multiple regression analyses revealed that female sex (OR = 2.2, 95% CI [1.3-3.7]) and perceived low family income (OR = 2.4, 95% CI [1.1-5.1]) were associated with neck pain at the 11-year follow-up. Girls and boys with a perceived low family income had a 29% and 17% higher probability of neck pain than adolescents with a perceived high family income. The risk profiles in both samples showed that co-occurrence of risk factors, such as headache/migraine, neck/shoulder pain, back pain, low physical activity level, loneliness, and perceived low family income cumulatively increased the probability of neck pain in young adulthood. These results underline the importance of taking a broad perspective when studying, treating, and preventing neck pain in adolescents.

Introduction

According to the Global Burden of Disease Study [1], neck pain is one of the most common musculoskeletal (MSK) disorders worldwide and is a top-five cause of years lived with disability in high and middle-income countries. Neck pain is reported as the most prevalent MSK pain site among adolescents [2, 3], commonly accompanied by low health-related quality of life, school absence, and avoidance of participation in activities and sports [3, 4]. Importantly, neck pain become persistent in many adolescents, but there is little knowledge regarding risk factors and causes of neck pain in these individuals [5]. The high prevalence of neck pain in adolescents [2, 6] is of great concern since studies suggest that individuals who develop pain and disabilities during adolescence are more likely to report these health complaints in adulthood [7-9].

Adolescence is a period of life characterised by significant changes in both the biology and the social environment. Development of MSK pain may be influenced by such changes and characteristics, for instance, sleeping disturbances [10], mental health problems [11], and a decreased physical activity level [12]. Social factors have been less studied, but peer-related stress [13] and loneliness [2] have shown associations with MSK pain in longitudinal studies of adolescents. We systematically reviewed longitudinal studies investigating risk factors for neck pain in young adults (18–29 years old). The searches revealed six studies analysing more than 50 risk factors, however no consistent risk factors were identified [14]. Cross-sectional studies have shown significant associations between neck pain and psychosocial factors, such as anxiety, depression, and perceived stress [15, 16]. Studies of adults indicate that risk factors for neck pain often encompassing a range of biopsychosocial factors [17] and apparently, there are differences depending on the inclusion of participants with a presence or an absence of neck pain at baseline [17]. Identifying single risk factors and the co-occurrence of risk factors in adolescents will enable us to identify high-risk groups. Such knowledge will contribute to designing future preventive interventions with the aim of reducing the high burden of neck pain for both the society and the individuals affected. To the best of our knowledge, no previous studies have investigated co-occurrence of risk factors (risk profiles) for neck pain in adolescents.

The objective of this study was to investigate the associations between potential risk factors and risk profiles in adolescence and neck pain in young adulthood in an 11-year prospective population-based study.

Materials and methods

The current study used data from the North-Trøndelag Health Study (HUNT), a large prospective population-based cohort study conducted in North-Trøndelag County in Norway [18, 19]. The HUNT Study consists of four health surveys carried out with 11-year intervals, where all inhabitants of North-Trøndelag County above 13 years of age were invited to participate. The surveys are divided into Young-HUNT (13–19 years of age) [19] and HUNT (20 years of age and above) [18]. To answer our research questions, we have linked data from wave 3 and 4, i.e. Young-HUNT3 (2006–2008) and HUNT4 (2017–2019).

Participation in the HUNT study was voluntary, and all study participants signed a written consent form. Written consent from a guardian was required for participants under the age of 16 years. The Regional Committee for Medical and Health Research Ethics (2019/517/REK Midt) and the Norwegian Centre for Research Data (543422) approved the present study. The study protocol has been published at clinical-trials.gov (NCT04201366). Reporting of this study is following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [20] (S1 Table).

Study population

Adolescents between 13 to 19 years of age from the Young-HUNT3 Study were included. To investigate both first-onset neck pain and new episodes of neck pain, participants were divided into two samples. Sample I includes all participants with valid data from both time points (Young-HUNT3 and HUNT4 Studies). Sample II includes only those who reported “never/seldom” to neck/shoulder pain in Young-HUNT3 (pain-free at baseline). Individuals who reported juvenile arthritis were excluded (Fig 1). Of the 8122 adolescents who were included in the Young-HUNT3 Study, 1433 (17.6%) attended the HUNT4 Study (Sample I). In Sample II (those who were pain-free at baseline), 823 (11.0%) fulfilled the inclusion criteria, responded to follow-up, and were included in the analyses in this study. A considerable number of participants were not re-invited in HUNT4 because they moved from the Municipality, moved to another country, or died during follow-up (n = 2931 (36%)). Fig 1 illustrates the flow-chart of the study participants.

Fig 1

Flow-chart of study participants.

Procedure

The Young-HUNT3 data collection took place during school hours with a comprehensive questionnaire, physical tests, and measurements of height and weight. Adolescents not attending the school on the day of assessment received the questionnaire by mail. They were invited to do the physical examinations at a field station in the local area. The HUNT4 Study took place 11 years later. The participants received an invitation letter and were asked to complete the electronic questionnaire and undertake physical tests at a local field station.

Potential risk factors (Young-HUNT3)

Investigated risk factors were chosen based on previous research of neck and other MSK pain in adolescents and adults. Neck pain seems to have multifactorial causation consisting of a range of biopsychosocial factors, such as anthropometric factors, previous pain conditions [21-23], lifestyle factors [10], psychological factors [24], and social factors [2, 25].

Anthropometric factors

Height and weight were objectively measured by a trained nurse. Body mass index (BMI) was calculated as kg/m2. Age-adjusted cut-offs from Cole et al. (2012) defined the BMI categories: “thinness”, “normal weight”, and “overweight/obese” [26]. Due to the low number of participants located in the thinness group (4%), thinness and normal weight were merged into one category.

Pain

In Young-HUNT3, pain was measured with items developed by Mikkelson et al., which have shown good concurrent validity and test-retest reliability in adolescents [27]. Participants were asked: “How often have you had any of the below-listed pain during the last three months?” A body chart of 11 body regions accompanied the question. The body regions were headache/migraine, neck/shoulder pain, back pain (upper and lower back), chest pain, upper extremity pain (left and right arm), lower extremity pain (left and right leg), abdominal pain, and other pain. For each body region, response categories were on a five-point Likert scale from “never/seldom” to “almost every day”. A cut-off score of more than one day per week was set to distinguish between participants with frequent pain and those with infrequent pain. Pain in each specific region was investigated as single risk factors.

To investigate if several pain sites in adolescence was a risk factor for neck pain in young adulthood, we created the variable number of pain sites by summarising all the 11 body regions. The number of pain sites was categorised into “no pain”, “one pain site”, “two pain sites” and “three or more pain sites” due to a low number of participants having more than three pain sites.

Lifestyle factors

Sleep problems, defined as having difficulty falling asleep at night, was measured on a four-point Likert scale ranging from “almost every night” to “never”. This variable was recoded into “never”, “seldom” or “almost every night”. This question is made by the Norwegian Institute of Public Health, inspired by similar questions from other health studies, but is not formally validated.

Physical activity was assessed with a question adapted from the World Health Organization Health Behaviour in Schoolchildren (HBSC) study [28]. The question has showed to correlate with cardiovascular fitness (r = 0.39), especially for girls (r = 0.55) [29]. Participants were asked how many days a week outside school hours they play sports or exercise to the point where they breathe heavily and/or sweat. This question had seven response categories ranging from “never” to “every day”. The response alternatives were operationalised into three levels: “one day a week or less (low level)”, “two to three days a week (moderate level)”, and “four days a week or more (high level)” as in a previous study [30].

Psychological factors

A five-item short version of the Symptoms Checklist (SCL-5) was used to measure symptoms of psychological distress, which is validated in Norwegian adolescents [31, 32]. This questionnaire consisted of five questions measuring whether the adolescents had been bothered with feelings of “fear or anxiety”, “tension or restlessness”, “hopelessness about the future”, “dejection or sadness”, and/or “excessive worry”. These checklist items were scored using a four-point Likert scale ranging from “not troubled” to “very much troubled”, referring to symptoms the previous two weeks. Higher scores indicate a higher level of psychological distress. The SCL-5 has demonstrated high reliability and high correlation with SCL-25 and SCL-10 [32], which have been validated in adolescents [33]. A cut-off score of ≥ 2.0 defined the presence of psychological distress, as suggested in one study [32].

Self-esteem was measured with four questions from the Rosenberg self-esteem scale (RSE) [34] and used as a continuous variable in the analyses. Each question was scored on a four-point scale ranging from “strongly agree” to “strongly disagree”. The short version of the RSE has shown a high correlation with the full version [35], which has demonstrated good validity in adolescents [34].

Social factors

Resilience was measured with eight questions from the Resilience Scale for Adolescents (READ) [36]. READ has shown acceptable validity in Norwegian adolescents [37]. The subscales social competence and family cohesion from the original questionnaire were used based on recommendations from the original developers. Social competence included four questions regarding their ability to: make other people feel comfortable around them, find new friends, talk to new people, and find something fun to talk about. Family cohesion included questions regarding shared family values, well-being within the family, shared positive expectations, and support of each other. Each question was rated on a five- points Likert scale ranging from “I totally agree” to “I totally disagree”. A higher score indicates high resilience.

Loneliness was measured with the question: “do you often feel lonely?” with five response alternatives that were transformed into three categories: “often/very often”, “sometimes”, “seldom or never”. This one-item question has been employed in one study measuring loneliness in adolescents [2], but is not formally validated.

The perceived family income was measured with one question from the HBSC study [28] asking: “How well off do you think your family is compared to most others?” The responses were: “about the same as most others”, “better financial situation”, and “worse financial situation”. This question has shown correspondence with parents’ education and parents’ work affiliation in a previous Norwegian study [38], but is not formally validated.

Outcome measures (HUNT4)

The primary outcome was neck pain measured at the 11-year follow-up (young adulthood). Neck pain was defined when lasting for three consecutive months or more during the last year and based on the question: “In the last year, have you had pain or stiffness in muscles or joints that has lasted at least three consecutive months?” The responses were yes or no. If participants answered yes, they were asked “where have you had this pain or stiffness”, accompanied by a body chart divided into different body regions. Participants who answered yes to pain and marked on neck in the chart were identified as cases in this study.

Statistical analyses

Continuous variables describing the study samples were reported with means and standard deviations (SD) when normally distributed and medians and ranges if they had skewed distributions. Categorical variables were reported as counts and percentages. Bivariate analyses of baseline characteristics were conducted to investigate possible differences between responders and non-responders. The chi-square test was used to compare categorical variables, independent sample t-test for normally distributed continuous variables, and Mann Whitney U test for pairs of data with skewed distribution.

We used univariate binary logistic regression analyses to analyse crude associations between each potential risk factor and neck pain. Variables with a p-value ≤ 0.1 in these univariate analyses were included in a multiple model using a backward stepwise selection [39] (S2 Table). P-values ≤ 0.05 were considered statistically significant in the multiple regression models. The results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Assessment of collinearity was conducted before the inclusion of variables in the multiple models. Missing data on potential risk factors was first handled by multiple imputations. The univariate analyses with imputed data showed similar results as the complete case analyses presented in the paper.

Risk profiles for neck pain in young adulthood were identified by converting the coefficients from the multiple regression analyses into probabilities given different combinations of significant risk factors using the following formula [40]: where b0, b1x1, b2x2, b3x3, b4x4, b5x5, b6x6 were the significant risk factors from the final multiple regression model.

Risk matrices were used to visualise the results, as reported in previous studies [41, 42]. The matrices are presented separately for girls and boys. All analyses were conducted using SPSS statistical software (SPSS Inc, Chicago, IL, USA).

Results

Demographics of study participants

Baseline characteristics are presented in Table 1. The mean age was 16 years (SD 1.8), and there was a higher proportion of girls (63% in Sample I and 57% in Sample II). Most study participants reported moderate to high physical activity level and a BMI within a normal weight range. The prevalence of neck/shoulder pain in all study participants (Sample I) was 18.1% (95% CI [16-20]). Headache/migraine was the most prevalent pain condition. The proportions of missing values for risk factors ranged from 0.9% to 13%.

Table 1

Baseline characteristics of study participants.

Characteristics at baseline	Sample I	Sample II
	N = 1433	N = 832
Age (yr) mean, (SD)	15.9 (1.8)	15.8 (1.7)
Sex, female n (%)	912 (63.6)	479 (57.6)
Perceived family income, n (%)
Better	215 (15.0)	127 (15.3)
Average	1006 (70.2)	598 (71.9)
low	118 (8.2)	59 (7.1)
Missing	94 (6.6)	48 (5.8)
BMI (kg/m2), n (%)
Normal	1037 (72.4)	621 (74.6)
Overweight/obese	315 (22.0)	161 (19.4)
Missing	81 (5.7)	50 (6.0)
School type, n (%)
Middle school students, n	808 (56.4)	489 (58.8)
High school students, n	592 (41.3)	326 (39.2)
Missing	33 (2.3)	17 (2.0)
Subjective health, n (%)
Good	1283 (89.5)	783 (94.1)
Poor	137 (9.6)	44 (5.3)
Missing	13 (0.9)	5 (0.6)
Neck/shoulder pain, n (%)
Often¥	259 (18.1)
Missing	25 (1.7)
Headache/migraine, n (%)
Often¥	339 (23.7)	118 (14.2)
Missing	26 (1.8)	6 (0.7)
Back pain, n (%)
Often¥	266 (18.6)	58 (7.0)
Missing	40 (2.8)	10 (1.2)
Number of pain sites, n (%)
0	668 (46.6)	536 (64.4)
1	237 (16.5)	142 (17.1)
2	142 (9.9)	57 (6.9)
3 or more	213 (14.9)	22 (2.6)
Missing	173 (12.1)	75 (9.0)
Physical activity level, n (%)
High level	526 (36.7)	329 (39.5)
Moderate level	513 (35.8)	299 (35.9)
Low level	372 (26.0)	190 (22.8)
Missing	22 (1.5)	14 (1.7)
Psychological distress, n (%)
<2.00	1124 (78.4)	730 (87.7)
≥2.00	266 (18.6)	80 (9.6)
Missing	43 (3.0)	22 (2.6)
Loneliness, n (%)
Often	119 (8.3)	41 (4.9)
Sometimes	319 (22.3)	152 (18.3)
Seldom	899 (62.7)	586 (70.4)
Missing	96 (6.7)	53 (6.4)
Self-esteem, mean (SD)	8.0 (2.4)	8.4 (2.3)
Missing	77 (5.4)	42 (5.0)

Sample I = all participants, Sample II = pain-free participants at baseline.

yr, year; SD, standard deviation; BMI, body mass index.

¥ Pain at least once per week during the last three months not related to any known disease or injury Symptom check list (1–4), Rosenberg self-esteem scale (0–12).

Analyses comparing our Sample I with those lost to follow-up showed that statistically significantly more males than females were lost to follow-up (52% vs 47%), the non-responders had a higher baseline physical activity level, and higher baseline self-esteem compared to responders (S3 Table).

Neck pain in young adulthood

At follow-up, 18.4% (95% CI [16-20]) of all respondents reported neck pain (Sample I). Among the pain-free adolescence at baseline (Sample II), 12.1% (95%CI [10-14]) reported neck pain at follow-up. Thirty-six percent of those with neck/shoulder pain at baseline had neck pain at follow-up.

Risk factors for neck pain in all study participants (Sample I)

In univariate analyses, female sex, high BMI, perceived low family income, headache/migraine, neck/shoulder pain, back pain, abdominal pain, three or more pain sites, low physical activity level, sleeping problems, psychological distress, low family cohesion, loneliness, and self-esteem were significantly associated with neck pain at the 11-year follow-up (S2 Table). The multiple logistic regression analyses showed that female sex, headache/migraine, neck/shoulder pain, back pain, low physical activity level, and loneliness were all independently statistically significantly associated with neck pain at the 11-year follow-up (Table 2).

Table 2

Multiple analysis of the association between potential risk factors in adolescence and persistent neck pain in young adulthood.

	Association with neck pain
	Sample I (n = 1433)	Sample II (n = 832)
Variables	OR and 95% CI	OR and 95% CI
Sex
Male	1.0	1.0
Female	1.9 (1.3–2.9)*	(1.3–3.7)*
Perceived family income
Average		1.0
Better		1.3 (0.6–2.5)
Worse		2.4 (1.1–5.1)*
Headache/migraine
Seldom	1.0
Often¥	1.7 (1.2–2.6)*
Neck/shoulder pain
Seldom	1.0
Often¥	2.0 (1.3–3.0)*
Back pain
Seldom	1.0
Often¥	1.5 (1.0–2.4)*
Physical activity
High level	1.2 (0.8–1.8)
Moderate level	1.0
Low level	1.6 (1.0–2.5)*
Loneliness
Seldom	1.0
Sometimes	1.2 (0.9–2.0)
Often/very often	2.0 (1.2–3.5)*

Sample I = all participants, Sample II = pain-free participants at baseline.

All significant variables were adjusted for each other.

1.0 = reference category.

*Variables significantly associated with persistent neck pain.

¥ Pain at least once per week during the last three months not related to any known disease or injury.

Risk factors for neck pain in the study participants pain-free at baseline (Sample II)

When assessing crude associations between potential risk factors and neck pain among those who were pain-free at baseline, our data revealed higher odds for neck pain for female sex, perceived low family income, headache/migraine, three or more pain sites, low physical activity level, sleeping problems, loneliness, and self-esteem (S2 Table). In the multiple logistic regression analyses, we found that female sex and perceived low family income remained significantly associated with neck pain at the follow-up (Table 2).

Risk profiles

Sample I

The highest probability of neck pain was found in participants with a low level of physical activity, loneliness, headache/migraine, back pain, and neck/shoulder pain (Fig 2). In these participants, the probability of having neck pain at follow-up was 67% (95% CI [65-70]) among the girls and 50% (95% CI [47-53]) among the boys. This was compared to 13% (95% CI [12-15]) among the girls and 7% (95% CI [6-8]) among the boys with moderate to high physical activity level, not feeling lonely and no headache/migraine, back pain or neck/shoulder pain.

Fig 2

Risk profiles for persistent neck pain in young adulthood in Sample I (n = 1433).

Sample I = all participants. Probabilities of persistent neck pain at follow-up (%, [95% CI]), red = highest risk profile.

Sample II

Fig 3 displays the risk profiles for neck pain in a visual risk matrix for those who were pain-free at baseline (Sample II). The probability of having neck pain at the 11-year follow-up was 29% (95% CI [26-32]) among the girls with perceived low family income and 17% (95% CI [14-20]) among the boys with perceived low family income.

Fig 3

Risk profiles for persistent neck pain in young adulthood in Sample II (n = 832).

Sample II = pain-free participants at baseline. Probabilities of persistent neck pain at follow-up (%, [95% CI]), red = highest risk profile).

Discussion

This study found that female sex, low level of physical activity, loneliness, headache/migraine, back pain, and neck/shoulder pain in adolescence were risk factors for having neck pain in young adulthood in Norwegian adolescents. The co-occurrence of these risk factors during adolescence cumulatively increased the probability of neck pain in young adulthood. Among adolescents without neck/shoulder pain at baseline, significant risk factors were female sex and perceived low family income.

Our finding that participants with combinations of risk factors in adolescence had a cumulatively increased probability of neck pain in young adulthood is in line with a previous cross-sectional study investigating the relationship between lifestyle behaviour and chronic non-specific pain in Norwegian adolescents [43]. They found a gradually stronger association with a higher number of unhealthy variables (low physical activity level, sedentary behaviour, high BMI, smoking, and alcohol). As illustrated in the risk matrix, the highest probability of neck pain occurred when combining all the statistically significant variables from the multiple analyses, and the probability decreased when individuals had more favourable outcomes. One might speculate that it is the actual number of risk factors that increase the probability of neck pain, regardless of type. Girls had, in general, a higher probability of neck pain than boys regardless of the combinations of risk factors.

Previous systematic reviews of children, adolescents, and young adults have shown inconsistent results for sex as a risk factor for MSK pain [11, 14]. One systematic review found inconsistent results across three studies investigating sex as a risk factor for neck pain in young adults [14], and a meta-analysis of Huguet et al. found inconsistent results of sex as a risk factor for MSK pain in children and adolescents [11]. Huguet et al., however, identified in their subgroup analyses that these differences might be caused by different pain conditions (chronic, acute, or mixed) included in the studies. They found that clearly defined chronic/recurrent MSK pain was significantly associated with female sex. This is in line with our finding of sex as a risk factor for neck pain lasting three months or more. Many explanations have been proposed for sex differences, such as innate differences in visceral and somatic perception, lower pain threshold in girls, and differences in reporting and acknowledgement of discomfort [44]. Further, there are differences in physical growth and development, psychological maturation, and hormonal profile during adolescence. This might influence the reporting of neck pain [45].

Our finding that headache/migraine, neck/shoulder, and back pain in adolescence were associated with neck pain in young adulthood among Norwegian adolescents is supported in the literature [21, 46, 47]. The reasons for these associations are unclear, but changes caused by pain in one body site might influence other body sites, and share similar mechanisms. One explanation for pain in different body parts is the neurophysiological changes implicated in central sensitisation. Further, studies have shown alterations in pain processing after an episode of acute pain, which seems to influence pain persistence in adolescents [48]. Our finding of a high prevalence of neck/shoulder pain in adolescence and the impact early pain had on future pain indicate that pain develops early.

Contrary to previous studies [14, 21], we found that a low level of physical activity in adolescence was associated with neck pain in young adulthood (Sample I). Differences in measurement of physical activity and in activities conducted [49] may explain inconsistent findings. Another reason might be the possible fluctuations in physical activity level during the current study’s long follow-up period [50]. Finally, we could speculate if adolescents with a low physical activity level do more sedentary activities such as screen-based activities. Screen-based activities have shown association with neck pain in one previous study [51].

Our finding that loneliness was associated with neck pain (Sample I) is in line with results from two Scandinavian cross-sectional studies investigating associations between loneliness related to spinal pain [2] and headache in adolescents [52]. Other social determinants, such as bullying and peer-related stress, have been associated with MSK pain in previous longitudinal studies [13, 53]. One explanation for these associations might be commonalities in the neurobiology seen in both “social pain” and physical pain. A study using functional magnetic resonance imaging found that social exclusion activated the same brain regions similar to physical pain [54]. Further, lonely adolescents could be more affected by negative emotions and be less able to cope with pain than adolescents with healthy social relationships. Studies of patients with chronic pain show that a lack of perceived social support is associated with higher pain intensity [55].

In line with other studies investigating associations between low socioeconomic status and economic stress in MSK pain in children, adolescents [11], and adults [56], we found an association between perceived low family income and neck pain in young adulthood (Sample II). However, this study’s measurement of socioeconomic status is different than most other studies, including the adolescent’s self-perceived family income rather than measuring socioeconomic status using parent’s education or work status. It is essential to consider the cultural aspect of this question. In a country like Norway with a high welfare standard, perceived low family income may be more related to possibilities for social participation rather than poverty related to having access to water, food, or healthcare. Thus, our results might be more related to the social aspects of having a low family income, such as lower possibilities of social participation in different activities.

Analysis derived from Sample I and Sample II revealed different risk factors, except for sex. An explanation for these results can be that Sample II excluded those with neck/shoulder pain at baseline. Previous studies have shown that adolescents experiencing pain have other illness perceptions or health behaviours than those who are pain-free. This includes withdrawal from social [57, 58] and pain-provoking physical activities [3, 58], reduced sleep quality [58, 59], decreased quality of life [4], and lower psychosocial well-being [2]. These factors might influence future pain experience [60]. Another reason for different results between the two samples might be lack of statistical power due to the sample sizes (1422 vs 832). For instance, Sample II included few cases who experienced loneliness (n = 41), back pain (n = 58), and headache/migraine (n = 118). Also, by excluding participants with a previous episode of neck pain, we probably excluded participants with other pain sites. This might explain lack of statistical significance for headache/migraine and back pain.

Psychological distress and sleeping difficulties did not reach statistical significance in our multiple analyses. This is contrary to findings from previous studies [10, 61]. Potential explanations may be different measurements used, different follow-up periods, and different statistical models.

Strengths and limitations

The strengths of this study are the prospective design, and the large sample size at baseline. The novelty of this study is our analytic approach of combining risk factors in risk profiles, and arranging the probability of having neck pain in young adulthood for given combinations of risk factors using risk matrices. To our best knowledge, this is the first study investigating risk profiles for neck pain in any age group. One limitation of this study is the high loss to follow-up (82%). The participants lost to follow-up differed significantly in sex, physical activity level, and self-esteem at baseline. However, even though participants lost to follow-up were statistically different regarding physical activity and self-esteem, the difference was low (0.2% difference in self-esteem and 2.3% difference in low physical activity level), probably not of clinical relevance. Furthermore, we did not have data on socioeconomic or pain status at follow-up for non-responders. Nevertheless, 36% of participants lost to follow up were assumed to be missing completely at random as they either died or emigrated between the two follow-ups.

The 11-year follow-up period forces us to be careful with interpretations of the associations, as we do not have information on changes in lifestyle, education, work, health status, pain, or injuries during follow-up. This is especially relevant since the transitional stage from adolescence to young adulthood is characterised by developmental changes in the social environment, lifestyle, work situation, and final biological and psychological maturation [62-64]. Furthermore, the low number of boys compared to girls in this study could have influenced statistical power and resulted in a type II error for boys, and it precluded stratification by sex in the model building. The Samples are not mutually exclusive, including individuals with and without neck pain in Sample I. The use of non-validated, single items for loneliness, sleep, and perceived family income may have biased the associations. The question measuring physical activity level has shown moderate correlation with cardiovascular fitness, but low correlation with objectively measured total energy expenditure and physical activity level [29]. Future studies should investigate variables such as physical activity, sleep, and socioeconomic status with objective measures to provide more valid measurements. Our findings should be validated in future longitudinal studies.

Implications

The risk profile analyses illustrated that combinations of selected risk factors in adolescence cumulatively increased the probability of developing neck pain in young adulthood. This highlights the importance of investigating combinations of risk factors to identify high-risk groups and to develop targeted prevention programs. Risk factors such as physical activity and loneliness are of special importance as these are modifiable. Our results substantiate the importance of promoting universal access to moderate and high physical activity in adolescents and motivating and facilitating adolescents who are already active to stay active. This is especially important since there is a trend towards decreased physical activity level through adolescence and young adulthood [50]. Moreover, physical activity has the potential to reduce existing neck pain [65], and may contribute to a higher participation in teams and sporting clubs, hence increase social access to social support and prevent loneliness [66]. For health care providers, risk profiles could contribute to identifying adolescents who are most at risk of developing neck pain.

Conclusion

In this prospective cohort study, we found that combinations of risk factors in adolescence cumulatively increased the probability of neck pain in young adulthood. Adolescents with co-occurring pain, loneliness, and inactivity are at a particularly high risk of having neck pain in young adulthood. Further, the risk is increased also for those with perceived low family income, especially girls. Targeting risk profiles in public health policy and efforts, primary health care and future intervention studies might contribute to reduce the burden of neck pain in younger populations.

STROBE statement—Checklist of items that should be included in reports of observational studies.

(DOCX)

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Univariate analyses of the association between potential risk factors in adolescence and persistent neck pain in young adulthood.

(DOCX)

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Analyses of baseline characteristics of study participants and participants lost to follow-up.

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HUNT4, Norwegian.

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HUNT4, English.

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Young-HUNT3, Norwegian.

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Young-HUNT3, English.

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26 Apr 2021

PONE-D-20-32895

Risk factors and risk profiles for neck pain in young adults: prospective analyses from adolescence to young adulthood - The North-Trøndelag Health Study

PLOS ONE

Dear Dr. Jahre,

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3) Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

4)  We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

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Reviewers' comments:

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1:

The manuscript “Risk factors and risk profiles for neck pain in young adults: prospective analyses from adolescence to young adulthood - The North-Trøndelag Health Study”. As a result of this study, The risk profiles in both samples showed that co-occurrence of risk factors, such as headache/migraine, neck/shoulder pain, back pain,low physical activity level, loneliness, and low family income cumulatively increased the probability of neck pain in young adulthood. Although the study is relevant and meticulously crafted, there are four issues that needs addressing by authors before publication.

* In the introduction, the emphasis on the originality of the study is not properly made. this issue should be underlined before the purpose

* In the discussion part, cultural differences in comparisons with other studies should be highlighted. Are these studies done with similar cultures?

*The reason for the low physical activity or the effect of this lowness on muscle strength and its relation with the neck muscles can be examined. Could the increase in internet usage be a risk factor in this regard?

*İt can increase internet usage in loneliness. Can this study be compared and discussed with the studies that have been done in the past when there was no internet use?

Reviewer #2:

I have had the privilege of reviewing the manuscript entitled: Risk factors and risk profiles for neck pain in young adults: prospective analyses from adolescence to young adulthood - The North-Trøndelag Health Study. The authors set out to investigate risk factors for neck pain in adolescents and young adults using a prospective design. This is a very good manuscript and I would like to start off with congratulating the authors for that. It is clear, well written and to-the-point.

I do have some comments that I would like the authors to address before the manuscript is ready for publication.

P1 L56-57. I’m not sure I follow the argument that because previous studies have found that daytime tiredness and use of text messages are risk factors for neck pain, that you should investigate it further? Can you please elaborate more on this?

P7 L194. I imagine that the perceived family income will be highly affected by the area in which the participants live and the people they are mostly around. I this a validated question?

P7. I like your thorough explanations of all your exposures and outcomes. Very nice!

P11 L271. S2 Table is a table of comparison between responders and non-responders and not the univariate analyses. Please correct.

P13 L315-316. Please use “Perceived family income” instead of “Family income” throughout the manuscript.

P14 L389-391. I think this statement is somewhat far-fetched. What mechanisms in the muscles are you referring to? Please justify this with more that one reference in your local language.

P15 L361. Many of your exposures are self-reported even though some could have been quantified e.g. physical activity, family income etc. Please elaborate on the implications and arguments of this choice.

P17 L415. Please elaborate more on the differences between the responders and non-responders. As stated in line 242 the non-responders have higher level of physical activity and higher self-esteem. This would push the group towards less pain if the non-responders were included. I think this is a crucial part of your study, so I would expect you to have an in-depth discussion about it.

Reviewer #3:

GENERAL COMMENT

Thank you for the invitation to review this paper. The paper has evaluated a critical aspect of possible risk factors for neck pain in adolescents. Although it has an apropriate methodology and interesting reuslts some critical issues were identified. Introduction, Discussion and Limitations presented with some critical weaknesses that need authors attention if a re-submission will be considered. Authors should make sure that the manuscript is read and corrected by a native English- speaker. This is very important to ensure that the presenation and key messages are clear. Several comments highlight difficulties in the way that the manuscript is preseneted.

Introduction

Line 50: Authors refer to studies, however, the reference at the end of the sentence includes one relative old study about back pain in adolescents. Further justification of the statement must be included.

line 52-59: Authors description decreases the strength of the statement. The paragraph ends with the need of the research question; still, needs a better flow. Please, rephrase.

Materials and Methods

Line 97: Was this the only exclusion criteria used? If not, please, provide all exlusion/inclusion criteria of the study.

Lines 143-144: is this a post-hoc analysis? If yes, please state it.

Lines 155-156 Please provide results of the acceptable validity and reliability in parenthesis

It seems that the current questionnaire has a substantial reliability only for girls while based on the original study especially among girls. None of the questionnaires however seemed to be a valid instrument for measuring physical activity compared to TEE and PAL in adolescents. This should be discussed as a limitation in the study.

Line 173 Other study or studies? Please be precise when justifying a statement for the outcome measures of the study.

Results

Table 1: Abbreviations of BMI, yr, SD etc. are missing

Discussion

Line 332: what type of pain? neck pain?

Line 333: which unhelathy variables?

Line 337: Can you identify which factor may play a more critical role? This could make a difference

Line 359-360: Where this assumption comes from? Please, explain and justify

Line 362: Refernces should be placed after the comma

Line 367: Can you justify this assumption?

Lines 356-370 You should use a separate sentence as this section because it is difficult to read.

Lines 390 Why muscles are affected? Do you have such indication/measurement from the results of the present study. This statement is very debatable for pain neuroscience. Please, re-consider it

Line 394 Which are these studies?Please use references.

Line 401 Did this factor affected your Power analysis?

Lines 405-408 paragraph should be rephrased. It is vague and difficult to digest.

Line 411-427

Limitations: Have you considered spinal deformities as a possible risk factor? During the 11 years several other factors like whiplash injuries, workload etc. may have changed the presence or recurrence neck pain. Could have these factors been systematic errors affecting results?

Line 417 How much losses to-follow-up ?

Lines 421-422 This issue should be discussed further in discussion and compared to other studies.

Conclusion

Lines 433-436 Are these factors associated? If physical activity is high other factors are less critical? Have you considered if parental socioeconomic status affects adolescents participation in physical activity due to motivation etc.?

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Reviewer #1: Yes: Nuray ALACA

Reviewer #2: Yes: Dr. Henrik Koblauch

Reviewer #3: Yes: Stefanos Karanasios

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

27 May 2021

Journal Requirements:

1) Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Author response and action: We thank the editor for highlighting the importance of following the journals guidelines. We have now thoroughly gone through the journal’s requirements and edited the manuscript accordingly.

2) You indicated that you had ethical approval for your study. In your Methods section, please ensure you have also stated whether you obtained consent from parents or guardians of the minors included in the study or whether the research ethics committee or IRB specifically waived the need for their consent.

Author response:

We thank editor for this comment. We agree that this is important information that should be included in the method section. We have provided this information.

Author action: Page 2, Line number 85-87: Participation in the HUNT study was voluntary, and all study participants signed a written consent form. Written consent from a guardian was required for participants under the age of 16 years.

3) Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

Author response and action: Thank you for this comment. The questionnaires used in this study was in Norwegian. The HUNT Research Centre has developed English questionnaires to inform foreign researchers about the study methods, but these are not validated for research in English. We have provided these questionnaires used in both English and Norwegian as Supporting Information.

4) We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

Author response: We acknowledge that data sharing is important. Unfortunately, due to restrictions from the Regional Committee for Medical and Health Research Ethics in accordance with Norwegian law, the participants in the HUNT study have not given consent to public sharing of their data. Therefore, data are only available upon request to the Data Access Committee at the HUNT Research Centre. We included this information in the cover letter.

Author action: Data cannot be shared publicly because of restrictions from the Regional Committees for Medical and Health Research Ethics (post@helseforskning.etikkom.no) in

accordance with Norwegian law, as participants in the HUNT survey have not given

consent to public sharing of their data. Therefore, these data are only available upon request to the Data Access Committee at HUNT Research Centre at hunt@medisin.ntnu.no.

________________________________________

Reviewer #1:

The manuscript “Risk factors and risk profiles for neck pain in young adults: prospective analyses from adolescence to young adulthood - The North-Trøndelag Health Study”. As a result of this study, The risk profiles in both samples showed that co-occurrence of risk factors, such as headache/migraine, neck/shoulder pain, back pain, low physical activity level, loneliness, and low family income cumulatively increased the probability of neck pain in young adulthood. Although the study is relevant and meticulously crafted, there are four issues that needs addressing by authors before publication.

1) In the introduction, the emphasis on the originality of the study is not properly made. this issue should be underlined before the purpose

Author comments: We are thankful to the reviewer for highlighting the need to make a clearer presentation of the study’s originality to the introduction. We agree with the reviewer and have made changes in the introduction.

Author actions: Page 1 and 2, Line number 67-72: Identifying single risk factors and the co-occurrence of risk factors in adolescents will enable us to identify high-risk groups. Such knowledge will contribute to designing future preventive interventions with the aim of reducing the high burden of neck pain for both the society and the individuals affected. To the best of our knowledge, no previous studies have investigated co-occurrence of risk factors (risk profiles) for neck pain in adolescents.

2) In the discussion part, cultural differences in comparisons with other studies should be highlighted. Are these studies done with similar cultures?

Author response: Thank you for this suggestion. We agree with the reviewer that cultural differences might play an important role when comparing results across studies. We provided information of which countries the comparable studies came from and added a sentence about cultural differences regarding the socioeconomic perspective in the discussion.

Author action:

Page 14, Line number 334: Norwegian adolescents

Page 15, Line number 373: Scandinavian studies

Page 16, Line number 389-393: It is essential to consider the cultural aspect of this question. In a country like Norway with a high welfare standard, perceived low family income may be more related to possibilities for social participation rather than poverty related to having access to water, food, or healthcare. Thus, our results might be more related to the social aspects of having a low family income, such as lower possibilities of social participation in different activities.

3) The reason for the low physical activity or the effect of this lowness on muscle strength and its relation with the neck muscles can be examined. Could the increase in internet usage be a risk factor in this regard?

Author comment: We understand this comment is related to the discussion on physical activity. We agree that internet use could be associated with decreased muscle strength and thus also neck muscles, and in that way may be a potential risk factor for neck pain. However, we do not have access to internet usage in this sample. In addition, internet usage among adolescents has probably changed considerably since 2006-2008, and data from that time point may not be relevant for today’s population regarding internet use.

4) İt can increase internet usage in loneliness. Can this study be compared and discussed with the studies that have been done in the past when there was no internet use?

Author comment: Thank you for highlighting the influence of internet. Because baseline data was measured in 2006-2008, we will be careful to discuss internet use as this has changed enormously the last decade. Further, there are not many studies investigating loneliness in relationship with neck pain in adolescents, so comparison with more studies from the past is difficult.

Reviewer #2:

I have had the privilege of reviewing the manuscript entitled: Risk factors and risk profiles for neck pain in young adults: prospective analyses from adolescence to young adulthood - The North-Trøndelag Health Study. The authors set out to investigate risk factors for neck pain in adolescents and young adults using a prospective design. This is a very good manuscript and I would like to start off with congratulating the authors for that. It is clear, well written and to-the-point.

I do have some comments that I would like the authors to address before the manuscript is ready for publication.

1) P1 L56-57. I’m not sure I follow the argument that because previous studies have found that daytime tiredness and use of text messages are risk factors for neck pain, that you should investigate it further? Can you please elaborate more on this?

Author response and actions: We are thankful to the reviewer for highlighting the need for making this paragraph clearer. We agree that our argument of why it is important to investigate neck pain is not clear. After further consideration, we decided to remove the paragraph, as we do not think it adds something necessary to the introduction.

2) P7 L194. I imagine that the perceived family income will be highly affected by the area in which the participants live and the people they are mostly around. Is this a validated question?

Author response: Thank you for highlighting the need to specify this. We agree with the reviewer that perceived family income probably is affected by the living area. We provided a sentence regarding validation in the method section and added a sentence regarding cultural differences in the discussion section.

Author actions:

Page 7, Line number 196-197: This question has shown correspondence with parents’ education and parents’ work affiliation in a previous Norwegian study (39), but is not formally validated

Page 16, Line number 389-393: It is essential to consider the cultural aspect of this question. In a country like Norway with a high welfare standard, perceived low family income may be more related to possibilities for social participation rather than poverty related to having access to water, food, or healthcare. Thus, our results might be more related to the social aspects of having a low family income, such as lower possibilities of social participation in different activities.

3) P7. I like your thorough explanations of all your exposures and outcomes. Very nice!

Author response: We thank the reviewer for this positive comment!

4) P11 L271. S2 Table is a table of comparison between responders and non-responders and not the univariate analyses. Please correct.

Author response: Thank you for pointing out this important mistake.

Author action: We replaced the table of responders and non-responders with the univariate analyses.

5) P13 L315-316. Please use “Perceived family income” instead of “Family income” throughout the manuscript.

Author response: Thank you for this comment. We agree with the reviewer.

Author action: We changed “family income” to “perceived family income” throughout the manuscript.

6) P14 L389-391. I think this statement is somewhat far-fetched. What mechanisms in the muscles are you referring to? Please justify this with more that one reference in your local language.

Author response and actions: Thank you for highlighting that this statement should be justified better. We agree that this is not well documented. Since reviewer three also questioned this sentence and recommended we reconsider it, we decided to remove it.

7) P15 L361. Many of your exposures are self-reported even though some could have been quantified e.g. physical activity, family income etc. Please elaborate on the implications and arguments of this choice.

Author response: We agree that more objectively measures of these variables could provide more valid results. Since we used already collected data from the HUNT study, we had to use the available variables. We included a sentence under the limitation section to highlight this issue.

Author action: Page 18, Line number 437-439: Future studies should investigate variables such as physical activity, sleep, and socioeconomic status with objective measures to provide more valid measurements.

8) P17 L415. Please elaborate more on the differences between the responders and non-responders. As stated in line 242 the non-responders have higher level of physical activity and higher self-esteem. This would push the group towards less pain if the non-responders were included. I think this is a crucial part of your study, so I would expect you to have an in-depth discussion about it.

Author response: Thank you for highlighting this important aspect. When conducting the statistical analyses of differences between responders and participants lost to follow-up, sex, physical activity, and self-esteem were statistically significantly different. However, these differences were small regarding physical activity level (2.3% difference) and self-esteem (0.2% difference), so we assume that this is not of any clinical relevance or have affected the results. However, we agree with the reviewer that this should be clearly stated in the manuscript. We included a sentence under the strength and limitation section.

Author actions: Page 17, Line number 418-421: However, even though participants lost to follow-up were statistically different regarding physical activity and self-esteem, the difference was low (0.2 % difference in self-esteem and 2.3% difference in low physical activity level), probably not of clinical relevance.

Reviewer #3:

GENERAL COMMENT

Thank you for the invitation to review this paper. The paper has evaluated a critical aspect of possible risk factors for neck pain in adolescents. Although it has an appropriate methodology and interesting results some critical issues were identified. Introduction, Discussion and Limitations presented with some critical weaknesses that need authors attention if a re-submission will be considered. Authors should make sure that the manuscript is read and corrected by a native English- speaker. This is very important to ensure that the presentation and key messages are clear. Several comments highlight difficulties in the way that the manuscript is presented.

Introduction

1) Line 50: Authors refer to studies, however, the reference at the end of the sentence includes one relative old study about back pain in adolescents. Further justification of the statement must be included.

Author response: We thank the reviewer for highlighting this issue; we agree that this sentence need further justification. We included two more references of newer date after this statement.

Author actions: Page 1, Line 54: We included two more references (7 and 8)

2) line 52-59: Authors description decreases the strength of the statement. The paragraph ends with the need of the research question; still, needs a better flow. Please, rephrase.

Author response and actions: We are thankful to the reviewer for highlighting the need for making this paragraph clearer. We agree that our argument of why it is important to investigate neck pain is not clear in this section. After further consideration, we decided to remove the paragraph, as we do not think it adds something necessary to the introduction.

Materials and Methods

3) Line 97: Was this the only exclusion criteria used? If not, please, provide all exlusion/inclusion criteria of the study.

Author response: Thank you for this question. Yes, adolescents with juvenile arthritis were the only ones excluded from inclusion at baseline.

4) Lines 143-144: is this a post-hoc analysis? If yes, please state it.

Author response: Thank you for this question. No, this was not a post-hoc analysis.

This is how we categorized the variable, but the categorization was conducted after receiving the data.

5) Lines 155-156 Please provide results of the acceptable validity and reliability in parenthesis

It seems that the current questionnaire has a substantial reliability only for girls while based on the original study especially among girls. None of the questionnaires however seemed to be a valid instrument for measuring physical activity compared to TEE and PAL in adolescents. This should be discussed as a limitation in the study.

Author response: Thank you for highlighting the need for elaboration of this question’s weaknesses. We agree that this is highly relevant information and have provided additional information in the method section and in the discussion section.

Author actions: Page 5, Line 154-155: Physical activity was assessed with a question adapted from the World Health Organization Health Behaviour in Schoolchildren (HBSC) study (28). The question has showed to correlate with cardiovascular fitness (r=0.39), especially for girls (r=0.55)

Page 18, Line number 434-437: The question measuring physical activity level has shown moderate correlation with cardiovascular fitness, but low correlation with objectively measured total energy expenditure and physical activity level

6) Line 173 Other study or studies? Please be precise when justifying a statement for the outcome measures of the study.

Author response: Thank you for highlighting the importance of being precise; we changed to one study.

Author actions: Page 6, Line number 172: ….as suggested in one study

Results

7) Table 1: Abbreviations of BMI, yr, SD etc. are missing

Author response: Thank you for pointing this out. We agree that this should be included.

Author actions: We provided the abbreviations for yr, year; SD, standard deviation; BMI, Body mass index in the table legend.

Discussion

8) Line 332: what type of pain? neck pain?

Author response: This study investigated chronic non-specific pain. We specified this.

Author action: Page 14, Line number 333-334: ….non-specific pain in Norwegian adolescents

9) Line 333: which unhealthy variables?

Author response: Thank you for this comment. We added the unhealthy variables included in the study.

Author action: Page 14, Line number 334-336: They found a gradually stronger association with a higher number of unhealthy variables (low physical activity level, sedentary behaviour, high BMI, smoking, and alcohol).

10) Line 337: Can you identify which factor may play a more critical role? This could make a difference

Author response: Thank you for this question. We agree that this would be interesting to know. As seen in the risk matrix, female sex is the only variable in all the combinations with the highest probability of neck pain. Except for this, it seems like an increasing number of “risk factors” influence the probability of neck pain regardless of type. We have specified this in the discussion.

Author actions: Page 14, Line number 340-341: Girls had, in general, a higher probability of neck pain than boys regardless of the combinations of risk factors.

11) Line 359-360: Where this assumption comes from? Please, explain and justify

Author response: We agree that we should elaborate on this. We rewrote this sentence to make it clearer.

Author actions: Page 15, Line number 363-364: Our finding of a high prevalence of neck/shoulder pain in adolescence and the impact early pain had on future pain indicate that pain develops early.

12) Line 362: References should be placed after the comma

Author response: Thank you for pointing this out. We agree and placed the references earlier in the sentence.

Author action: Page 15, Line number 365: Contrary to previous studies (12, 20), we found that a low level of physical activity in adolescence was associated with neck pain in young adulthood (Sample I).

13) Line 367: Can you justify this assumption?

Author response: Thank you for this question. This sentence is speculation, and we do not have strong evidence to support this. Since we cannot justify this assumption, we decided to remove the sentence.

Author action: We removed the sentence,

14) Lines 356-370 You should use a separate sentence as this section because it is difficult to read.

Author response: Thank you for your comment, we agree with the reviewer that this paragraph is difficult to read. We rephrased the paragraph.

Author actions: Page 15, Line number 357-362: The reasons for these associations are unclear, but changes caused by pain in one body site might influence other body sites, and share similar mechanisms. One explanation for pain in different body parts is the neurophysiological changes implicated in central sensitisation. Further, studies have shown alterations in pain processing after an episode of acute pain, which seems to influence pain persistence in adolescents

15) Lines 390 Why muscles are affected? Do you have such indication/measurement from the results of the present study. This statement is very debatable for pain neuroscience. Please, re-consider it

Author response: Thank you for highlighting that this is very debatable for pain neuroscience. We do not have measurement from this study to support this assumption. We decided to remove this sentence from the manuscript.

Author action: We removed the sentence.

16) Line 394 Which are these studies? Please use references.

Author response: Thank you for this question and for highlighting the need for more references. We agree with the reviewer and have provided more references and rewritten the sentence.

Author action: Page 16, Line number 396-400: An explanation for these results can be that Sample II excluded those with neck/shoulder pain at baseline. Previous studies have shown that adolescents experiencing pain have other illness perceptions or health behaviours than those who are pain-free. This includes withdrawal from social (57, 58) and pain-provoking physical activities (3, 58), reduced sleep quality (58, 59), decreased quality of life (4), and lower psychosocial well-being (2). These factors might influence future pain experience (60).

17) Line 401 Did this factor affected your Power analysis?

Author response: Thank you for this question. Yes, a reduction in statistical power could be an explanation for our results. We included a sentence about this.

Author action: Page 16, Line number 400-401: Another reason for different results between the two samples might be lack of statistical power due to the sample sizes (1422 vs 832).

18) Lines 405-408 paragraph should be rephrased. It is vague and difficult to digest.

Author response: We agree that this paragraph was vague, so we rephrased it.

Author action: Page 17, Line number 406-409: Psychological distress and sleeping difficulties did not reach statistical significance in our multiple analyses. This is contrary to findings from previous studies (23, 61). Potential explanations may be different measurements used, different follow-up periods, and different statistical models.

19) Line 411-427

Limitations: Have you considered spinal deformities as a possible risk factor? During the 11 years several other factors like whiplash injuries, workload etc. may have changed the presence or recurrence neck pain. Could have these factors been systematic errors affecting results?

Author response: Thank you for this question. We acknowledge that there probably are other risk factors for neck pain that is not covered in this study. However, to the best of our knowledge, spinal deformities have not shown any previous association with neck pain in longitudinal studies of adolescents or young adults. There is, indeed, an important limitation that we do not have data during the 11-year follow-up. Thank you for pointing this out. We have now elaborated on this in the limitation section.

Author action: Page 18, Line number 425-430: The 11-year follow-up period forces us to be careful with interpretations of the associations, as we do not have information on changes in lifestyle, education, work, health status, pain, or injuries during follow-up. This is especially relevant since the transitional stage from adolescence to young adulthood is characterised by developmental changes in the social environment, lifestyle, work situation, and final biological and psychological maturation (62-64).

20) Line 417 How much losses to-follow-up ?

Author response: We agree that this is relevant information and provided the percent of loss to follow-up.

Author action: Page 17, Line number: 416-417 One limitation of this study is the high loss to follow-up (82%).

21) Lines 421-422 This issue should be discussed further in discussion and compared to other studies.

Author response: Thank you for this comment. We agree that this is important to discuss. We discussed this further in the limitation section.

Author action: Page 18, Line number 425-430: The 11-year follow-up period forces us to be careful with interpretations of the associations, as we do not have information on changes in lifestyle, education, work, health status, pain, or injuries during follow-up. This is especially relevant since the transitional stage from adolescence to young adulthood is characterised by developmental changes in the social environment, lifestyle, work situation, and final biological and psychological maturation (62-64).

Conclusion

22) Lines 433-436 Are these factors associated? If physical activity is high other factors are less critical? Have you considered if parental socioeconomic status affects adolescents participation in physical activity due to motivation etc.?

Author response: Thank you for these questions. We chose to have extra focus on the implications regarding physical activity as this is a modifiable variable and also have the potential to decrease neck pain and loneliness. We rephrased the sentence to make this more clear. The association between socioeconomic status and low physical activity level is not investigated in this study, and to the best of our knowledge, the evidence regarding this association is unclear in adolescents. We remove this from the paragraph.

Author action: Page 18-19, Line number 445-450: Risk factors such as physical activity and loneliness are of special importance as these are modifiable. Our results substantiate the importance of promoting universal access to moderate and high physical activity in adolescents and motivating and facilitating adolescents who are already active to stay active. This is especially important since there is a trend towards decreased physical activity level through adolescence and young adulthood.

________________________________________

Submitted filename: Response to reviewers.docx

Click here for additional data file.

22 Jul 2021

PONE-D-20-32895R1

Risk factors and risk profiles for neck pain in young adults: prospective analyses from adolescence to young adulthood - The North-Trøndelag Health Study

PLOS ONE

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Reviewer #3: Authors responded adequately to all reviewers suggestions and made essential improvements with their revised manuscript. Some minor changes should be made as follows

Line 52 Please provide a reference for the following statement if exists ‘The high prevalence of neck pain in adolescents …’

Line 224-228 Please provide a reference to justify the formula used

Line 326-330 Please specify that your findings are describing an association in adolescents in Norway

Line 355-356 Similar as above comment

Subsequently, a final decicion for approval should be supported

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Reviewer #1: Yes: Nuray ALACA

Reviewer #2: Yes: Henrik Koblauch

Reviewer #3: Yes: Stefanos Karanasios

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28 Jul 2021

Author comment: Thank you for the constructive comments. The suggested changes are conducted as described below.

1) Line 52 Please provide a reference for the following statement if exists ‘The high prevalence of neck pain in adolescents …’

Author comment: Thank you for this comment, we agree that this statement should be supported by references.

Author action:

Page 1, Line 52: We provided two references to support the statement that neck pain is prevalent in adolescents.

2) Line 224-228 Please provide a reference to justify the formula used

Author comment: Thank you for pointing this out.

Author action:

Page 8, Line 225: We inserted a references to justify the formula used.

3) Line 326-330 Please specify that your findings are describing an association in adolescents in Norway

Author comment: Thank you for highlighting this, we rewrote the sentence.

Author changes:

Page 13, Line 327: This study found that female sex, low level of physical activity, loneliness, headache/migraine, back pain, and neck/shoulder pain in adolescence were risk factors for having neck pain in young adulthood in Norwegian adolescents.

4) Line 355-356 Similar as above comment

Author comment: Thank you for highlighting this, we agree that this should be specified.

Author actions:

Page 15, Line 357: We rewrote the sentence: Our finding that headache/migraine, neck/shoulder, and back pain in adolescence were associated with neck pain in young adulthood among Norwegian adolescents is supported in the literature

Submitted filename: Response to reviewers.docx

Click here for additional data file.

29 Jul 2021

Risk factors and risk profiles for neck pain in young adults: prospective analyses from adolescence to young adulthood - The North-Trøndelag Health Study

PONE-D-20-32895R2

Dear Dr. Jahre,

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PLOS ONE

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2 Aug 2021

PONE-D-20-32895R2

Risk factors and risk profiles for neck pain in young adults: prospective analyses from adolescence to young adulthood - The North-Trøndelag Health Study

Dear Dr. Jahre:

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Academic Editor

PLOS ONE