Centers for Disease Control and Prevention guidelines were used to define categories of overweight and obesity based on measured height and weight (Fig. 1). Participants with factor activity between 6% and 49% of normal levels were considered to have mild, 1–5% moderate, and <1%, severe haemophilia [3]. Participants were grouped into three age categories: children 6–11 years; teens 12–19 years; and adults 20 years and older. Treatment type was classified as episodic if the patient received products only to treat bleeding complications since the last annual clinic visit. Individuals were considered to use prophylaxis if they received treatment products to prevent bleeding or re-bleeding either continuously or on an intermittent schedule. Persons with commercial or public health care coverage were considered to be insured. Participants who received treatment products intravenously outside the medical setting (such as an HTC or emergency department) were considered to use HI. HI was performed either by the patient, a family member, or a medical care provider, such as a home health professional. Those who infused factor without help from others, such as parents or medical care providers, were considered to use SI.

The prevalence of HI and SI (among those practising HI) was calculated for each level of demographic and clinical characteristics. Pearson’s chi-squared test or Fisher’s exact test were used to assess the statistical significance of associations in bivariate analyses. Logistic regression was used to assess the independent association of BMI with the use of HI and SI in multivariate analyses. Adjusted odds ratios (aOR) and 95% confidence intervals were computed. All statistical analyses were based on two-sided tests with a significance level of 0.05, and conducted using SAS 9.3 (SAS Institute, Cary, NC, USA).

The analysis was conducted in four parts: (i) Frequency distributions of BMI categories and prevalence of HI and SI were calculated. (ii) Bivariate relationships of infusion use with elevated BMI and other demographic or clinical characteristics were calculated using chi-squared tests. (iii) Multiple logistic regression models were developed to describe whether overweight and obesity were associated with the likelihood of HI and SI while adjusting for seven variables that were potential confounders: age, ethnicity, insurance status, haemophilia type and severity, treatment type and CVAD use. (iv) Controlling for the same confounders, quartic polynomial logistic regression models using age as a continuous variable were created to illustrate the impact of BMI and advancing age on the prevalence of HI and SI. Figures based on these models illustrate the mean predicted probability of using HI and SI with advancing age among the largest subset of the sample population. This subset (n = 4721; 43% of sample population) included the most commonly occurring characteristics: white ethnicity, haemophilia A, no CVAD and having health care coverage).

Overall, 36% of children, 38% of teens and 63% of adults had above-normal BMI. The prevalence of obesity as compared to overweight differed among adults and youth. A larger proportion of children and teens were obese (20% and 22% respectively) than were overweight (16% in both children and teens). Overweight (35%) affected a greater proportion of adults than did obesity (28%; P < 0.0001). Hispanic participants had the highest prevalence of elevated BMI among all ages. Multiple regression analysis among adults also revealed a significant association (P ≤ 0.0001) between increased BMI and mild haemophilic severity (Table 1).

Seventy per cent of male patients practised HI. Eight characteristics (Table 2) were associated (P < 0.0001) with increased HI use: age 12–19 (74%); African – American ethnicity (80%); severe haemophilia vs. moderate/mild disease (94% vs. 69% and 34%); haemophilia A vs. haemophilia B (72% vs. 65%); prophylaxis use (98% vs. 57%); CVAD use (95% vs. 68%) and normal or below-normal BMI (73%) vs. overweight (67%) and obesity (66%). These associations remained in the multivariable model. Although HI was associated with insurance coverage in the univariate analysis (P = 0.03, Table 2), this association diminished in the multivariate analysis (Table 4). Prophylaxis use is a confounder with severity, and we observed a trend effect between severity and HI use. Therefore, our analysis adjusted for both severity and treatment type; the effects of these interactions are illustrated in Figs 2 and 3.

Figures 2a and b compare the predicted probability of HI use by age and treatment regimen. Regardless of severity, HI use was more prevalent among persons using prophylaxis (Fig. 2a) than among those treating episodically (Fig. 2b). For prophylaxis users, a difference in HI use among age and BMI categories was clearly observed only among those with mild disease. Use of HI was highest among 20–29-year-olds for all BMI groups. The rate of HI use climbed steadily during childhood through the mid-20s, but fell as BMI and age increased. Among adults, HI use was highest (75%) among those of normal weight and lowest among the obese (63%). A trend of declining HI use with increasing BMI was also observed in teens (P = 0.057) and children (P = 0.040).

Self-infusion was practised by 44% of those infusing at home. Tables 2 and 3 illustrate the univariate association between demographic and clinical characteristics and prevalence of SI. Table 2 displays the prevalence of SI and HI. Table 3 highlights the reduced use of SI with increased BMI among adults and teens. This association is not apparent in Table 2 because of the inclusion of children aged 6–11, among whom there was no association between BMI and SI use. We observed a significantly higher SI prevalence (P < 0.0001, Table 2) among adults (71%); among those with severe haemophilia (vs. moderate/mild disease (47% vs. 41%, 40%); and among those using episodic vs. prophylactic treatment. The greater prevalence of SI use among persons on episodic treatment in Table 2 reflects the inclusion of children aged 6–11 (too young to self-infuse) using a prophylaxis. Table 3 demonstrates the increased prevalence of SI among teens and adults using prophylaxis compared to episodic treatment (teens: 35% vs. 27%; P < 0.0001) adults: 79% vs. 69%, P < 0.0001) There was no association between ethnicity (P = 0.13) or haemophilia type (P = 0.9) and SI use. Increased BMI was significantly associated with lower prevalence of SI among teens (P = 0.002) and adults (P = 0.005).

Home treatment affords immediate access to effective treatment. The ability to access home treatment has transformed the lives of haemophilic persons by reducing time to treatment and enabling adherence to prophylactic treatment. Prophylaxis involves frequent infusion of factor concentrate (1–4 times per week) and has been demonstrated to decrease episodes of joint bleeds and chronic arthropathy [2,16]. Home treatment has been shown to reduce pain and disability, hospitalizations, time lost from work or school, and to improve patients’ overall quality of life [17]. The probability graphs generated in this analysis (Fig. 2a and b) illustrate higher levels of HI use by those with moderate and severe disease and those using prophylaxis, after adjustment for other confounding variables.

Self-infusion allows patients to treat themselves conveniently at home, work, school, or while travelling. Bleeding episodes can be treated with minimal delay, a particularly important aspect of care for teenagers, who are often involved in sports and are physically very active. By facilitating timely treatment of a bleed, SI helps to preserve independence [18]. The increasing use of adult prophylactic regimens in developed countries adds to the need for SI skills [19]. We noted that SI use did not peak until 29–30 years among all severities, indicating that older teens and young adults may benefit from additional training.

This analysis suggests that obese persons with haemophilia are less likely to use HI and SI, possibly because of the increased difficulty of venipuncture caused by adiposity [6,7]. Additional studies designed to examine specific causes for the association between obesity and decreased use of HI and SI will advance our understanding of the interaction between these factors. The inability to perform HI and SI may lead to delayed treatment of bleeds, reduce the effectiveness of the treatment and place those with elevated BMI at increased risk of haemophilic complications.

Nearly 50% of haemophilic men were overweight or obese, similar to rates reported among the general US population by the 2007–2008 National Health and Nutrition Examination Survey [10,20].

Overweight and obese children are more likely to experience other poor health outcomes including high blood pressure, high cholesterol, impaired glucose tolerance, insulin resistance and type 2 diabetes, asthma, joint problems and fatty liver disease, and are at greater risk for social and psychological problems [21]. Moreover, youth with high BMI are more likely to become obese adults, a risk which increases with the degree of obesity [22,23].

Obese adults face a greater risk of hypertension, type 2 diabetes, coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnoea, and colon cancer [20]. Persons with bleeding disorders and elevated BMI may face unique health complications in addition to those faced by the general population. Above-normal BMI has been associated with reduced ROM in haemophilic persons in American and European studies and can increase the cost of care, as dosing of factor concentrate is based on actual body weight [11–13,24].

The increasing prevalence of obesity among young men will continue to be an issue for both the general and haemophilia populations as this cohort ages into adulthood [10,20]. NHANES data collected between 2009 and 2010 indicate that the prevalence of obesity among the general US population has now reached a plateau among most age groups except male adolescents, among whom the prevalence continues to rise [25]. The teen years are critical for haemophilic persons because during this period treatment preferences and skills (including SI) are developed. Obesity may present increasing challenges for haemophilia providers as they teach adolescents to self-infuse at an appropriate age and in the most effective way possible.

In addition, among both the sample and general US populations we note 15% of youth aged 6–19 have extreme obesity (BMI-for-age ≥97%), compared with only 4% of adults (BMI ≥ 40). Given our finding that obesity is strongly associated with decreased use of HI and SI and the fact that young persons with extreme obesity are likely to remain obese as adults, these individuals may, on reaching adulthood, experience even lower rates of HI and SI use than adults observed in the sample. Youth with extreme obesity may comprise a future high-risk group for whom interventions designed to increase the use of HI and SI may be beneficial.

Some limitations should be noted when interpreting the results of this analysis. Although we found statistically significant associations between elevated BMI, haemophilic severity and various treatments, we cannot determine from this cross-sectional data whether these associations are causal. Our sample population was derived solely from volunteer participants receiving care through federally funded HTCs, potentially limiting the application of our findings to all haemophilic persons, regardless of where they obtain care. The data reported in the UDC surveillance project were self-reported by the patient and treatment centre staff, but not confirmed with pharmacy or home care records. BMI as an indicator of obesity has limitations because it does not distinguish between fat mass and fat-free mass; however, studies demonstrate that although the association between BMI and body fat can be weak among persons with lean body mass (such as athletes), it is strong among those with higher BMI levels [26]. Small sample size may be an issue in analyses of subgroups stratified simultaneously by numerous variables, such as persons with mild disease using prophylaxis.