Cost-utility of fingolimod compared with dimethyl fumarate in highly active relapsing-remitting multiple sclerosis (RRMS) in England.

OBJECTIVE: The cost-effectiveness of new oral disease-modifying therapies (DMTs) has not been modeled in highly active (HA) relapsing-remitting multiple sclerosis (RRMS) requiring escalation therapy. This study sought to model the cost-effectiveness of fingolimod compared to dimethyl fumarate (DMF), for which relevant HA RRMS sub-group data were available, from the perspective of the National Health Service (NHS) in England. METHODS: A cohort Markov model based on Expanded Disability Status Scale scores, similar to previous model designs, was constructed. Published post hoc clinical data in the HA RRMS sub-groups were taken from the pivotal trials for fingolimod and DMF vs placebo. Utility data for each health state and for relapses were used in line with previous similar models. Published costs were inflated to NHS cost year 2013-2014 and UK list prices used for both drugs. Possible Patient Access Scheme (PAS) discount scenarios were investigated. RESULTS: In the base case, using list prices for each DMT, the average probabilistic incremental cost-effectiveness ratio (ICER) for fingolimod vs DMF was found to be £ 14,076, with a 73% chance of fingolimod being cost-effective at a willingness-to-pay threshold of £ 30,000. Scenario and sensitivity analyses showed that uncertainty in disability progression efficacy was a key model driver. The model was robust to other changes and the majority of PAS permutations do not contradict the base case finding of cost-effectiveness of fingolimod. CONCLUSIONS: In conclusion, fingolimod remains cost-effective in HA RRMS following the introduction of DMF to the UK market, and this paper supports the evidence that has led fingolimod to be the only oral DMT reimbursed for HA RRMS in England. This model supports the restriction imposed by National Institute for Health and Care Excellence (NICE) on DMF in HA RRMS and highlights the importance of considering different sub-groups of multiple sclerosis when performing health economic analyses.

No evidence of disease activity: indirect comparisons of oral therapies for the treatment of relapsing-remitting multiple sclerosis.

INTRODUCTION: No head-to-head trials have compared the efficacy of the oral therapies, fingolimod, dimethyl fumarate and teriflunomide, in multiple sclerosis. Statistical modeling approaches, which control for differences in patient characteristics, can improve indirect comparisons of the efficacy of these therapies. METHODS: No evidence of disease activity (NEDA) was evaluated as the proportion of patients free from relapses and 3-month confirmed disability progression (clinical composite), free from gadolinium-enhancing T1 lesions and new or newly enlarged T2 lesions (magnetic resonance imaging composite), or free from all disease measures (overall composite). For each measure, the efficacy of fingolimod was estimated by analyzing individual patient data from fingolimod phase 3 trials using methodologies from studies of other oral therapies. These data were then used to build binomial regression models, which adjusted for differences in baseline characteristics between the studies. Models predicted the indirect relative risk of achieving NEDA status for fingolimod versus dimethyl fumarate or teriflunomide in an average patient from their respective phase 3 trials. RESULTS: The estimated relative risks of achieving NEDA status for fingolimod versus placebo in a pooled fingolimod trial population were numerically greater (i.e., fingolimod more efficacious) than the estimated relative risks for dimethyl fumarate or teriflunomide versus placebo in each respective trial population. In indirect comparisons, the predicted relative risks for all composite measures were better for fingolimod than comparator when tested against the trial populations of those treated with dimethyl fumarate (relative risk, clinical: 1.21 [95% confidence interval 1.06-1.39]; overall: 1.67 [1.08-2.57]), teriflunomide 7 mg (clinical: 1.22 [1.02-1.46]; overall: 2.01 [1.38-2.93]) and teriflunomide 14 mg (clinical: 1.14 [0.96-1.36]; overall: 1.61 [1.12-2.31]). CONCLUSION: Our modeling approach suggests that fingolimod therapy results in a higher probability of NEDA than dimethyl fumarate and teriflunomide therapy when phase 3 trial data are indirectly compared and differences between trials are adjusted for.

Persistence with and adherence to fingolimod compared with other disease-modifying therapies for the treatment of multiple sclerosis: a retrospective US claims database analysis.

OBJECTIVE: Achieving therapeutic goals in multiple sclerosis (MS) requires strict adherence to treatment schedules. This retrospective study analyzed persistence with, and adherence to, fingolimod compared with injectable/infusible disease-modifying therapies (DMTs) in patients with MS. METHODS: Patients in the PharMetrics Plus™ US administrative claims database with at least one prescription for, or administration of, fingolimod, glatiramer acetate (GA), interferon (IFN), or natalizumab (index DMT) between October 1, 2010 and September 30, 2011 were included. Patients were naïve to index DMT (no claim in the previous 360 days) and had an MS diagnosis code within 360 days of the first index DMT prescription. Outcomes were persistence, risk of discontinuing index DMT (evaluated by a Cox proportional hazards model), adherence (measured using the medication possession ratio [MPR] and proportion of days covered [PDC] in patients with at least two index DMT prescriptions), and the risk of being non-adherent (MPR <80% and PDC <80%, assessed using a logistic regression model). RESULTS: The study included 3750 patients (fingolimod, n = 889; GA, n = 1233; any IFN, n = 1341; natalizumab, n = 287). Discontinuation rates (fingolimod, 27.9%; GA, 39.5%; IFN, 43.7%; natalizumab, 39.5%; all p < 0.001) and risk of discontinuation were significantly higher (hazard ratios vs fingolimod [95% confidence interval]: GA, 1.75 [1.49-2.07]; IFN, 2.01 [1.71-2.37]; natalizumab, 1.53 [1.22-1.91]) for patients receiving other DMTs compared with fingolimod. The risk of being non-adherent was also lower for patients in the fingolimod cohort than the other treatment cohorts, irrespective of whether non-adherence was defined as MPR <80% (p < 0.05 for all) or PDC <80% (p < 0.05 for GA and IFN). LIMITATIONS: As with all studies assessing real-world treatment patterns it is unclear if medications were used as prescribed. CONCLUSIONS: In a real-world setting, persistence with, and adherence to, oral fingolimod was higher than for injectable and infusible DMTs.

Healthcare resource use and relapses with fingolimod versus natalizumab for treating multiple sclerosis: a retrospective US claims database analysis.

OBJECTIVE: Healthcare resource utilization in patients with multiple sclerosis (MS) is linked to relapses and disease progression. This retrospective cohort database analysis compared healthcare resource use and proxy measures of relapse outcomes in patients with active disease who switched to fingolimod or natalizumab. METHODS: Using administrative claims data from the US PharMetrics Plus database, we identified patients with an MS diagnosis and a claim for fingolimod or natalizumab between 1 October 2010 and 30 June 2012 (index period) who had experienced a relapse (identified using a claims-based algorithm) and used other disease-modifying therapies (DMTs) in the previous year. Patients in the fingolimod and natalizumab cohorts were propensity score matched (1:1). MS-related inpatient stays, corticosteroid use and the proportion of patients experiencing claims-based relapses were assessed in the pre-index and post-index persistence periods. Time to first claims-based relapse in the post-index persistence period was assessed using a Kaplan-Meier curve. RESULTS: The study included 623 unmatched patients (299 and 324 patients in the fingolimod and natalizumab cohorts, respectively) and 370 matched patients (185 in each cohort). In the matched analysis, MS-related inpatient stays and corticosteroid use were similar in the fingolimod and natalizumab cohorts during the post-index persistence period, and were significantly reduced versus the pre-index period (p < 0.01). A similar proportion of patients in the fingolimod and natalizumab cohorts were free from claims-based relapses in the persistence period (68.1% and 68.6%, respectively). There was no significant difference in the likelihood of experiencing a claims-based relapse (p = 0.8696). LIMITATION: Identification of relapses is based on database claims rather than on clinical assessment. CONCLUSIONS: In analyses of patients with MS with a history of relapse and DMT use, fingolimod and natalizumab reduce healthcare resource utilization and have similar effectiveness in a real-world setting.

Relapse rates in patients with multiple sclerosis switching from interferon to fingolimod or glatiramer acetate: a US claims database study.

BACKGROUND: Approximately one-third of patients with multiple sclerosis (MS) are unresponsive to, or intolerant of, interferon (IFN) therapy, prompting a switch to other disease-modifying therapies. Clinical outcomes of switching therapy are unknown. This retrospective study assessed differences in relapse rates among patients with MS switching from IFN to fingolimod or glatiramer acetate (GA) in a real-world setting. METHODS: US administrative claims data from the PharMetrics Plus™ database were used to identify patients with MS who switched from IFN to fingolimod or GA between October 1, 2010 and March 31, 2012. Patients were matched 1∶1 using propensity scores within strata (number of pre-index relapses) on demographic (e.g. age and gender) and disease (e.g. timing of pre-index relapse, comorbidities and symptoms) characteristics. A claims-based algorithm was used to identify relapses while patients were persistent with therapy over 360 days post-switch. Differences in both the probability of experiencing a relapse and the annualized relapse rate (ARR) while persistent with therapy were assessed. RESULTS: The matched sample population contained 264 patients (n = 132 in each cohort). Before switching, 33.3% of patients in both cohorts had experienced at least one relapse. During the post-index persistence period, the proportion of patients with at least one relapse was lower in the fingolimod cohort (12.9%) than in the GA cohort (25.0%), and ARRs were lower with fingolimod (0.19) than with GA (0.51). Patients treated with fingolimod had a 59% lower probability of relapse (odds ratio, 0.41; 95% confidence interval [CI], 0.21-0.80; p = 0.0091) and 62% fewer relapses per year (rate ratio, 0.38; 95% CI, 0.21-0.68; p = 0.0013) compared with those treated with GA. CONCLUSIONS: In a real-world setting, patients with MS who switched from IFNs to fingolimod were significantly less likely to experience relapses than those who switched to GA.

Comparative effectiveness of fingolimod versus interferons or glatiramer acetate for relapse rates in multiple sclerosis: a retrospective US claims database analysis.

OBJECTIVE: Disease-modifying therapies, such as fingolimod, interferon (IFN) and glatiramer acetate (GA), have differing effects on relapse rates in patients with multiple sclerosis (MS), but little is known about the real-world differences in relapse rates with these treatments. This retrospective study assessed relapse rates in patients with active MS initiating fingolimod, IFN or GA therapy in a real-world setting. METHODS: Using administrative claims data from the US PharMetrics Plus database, we identified previously treated and untreated patients with MS who initiated fingolimod, IFN or GA treatment between 1 October 2010 and 31 March 2011 and had experienced a relapse in the previous year. A claims-based algorithm was used to identify relapses over the persistence period in patients with 540 days of post-index continuous enrolment. A logistic regression model assessed the probability of having at least one relapse and a generalized linear model estimated differences in annualized relapse rates (ARRs). RESULTS: The study enrolled 525 patients (fingolimod, n = 128; combined IFN/GA cohort, n = 397) of the 31,041 initially identified. Similar findings for fingolimod and IFN/GA were observed for the unadjusted proportion of patients experiencing relapses (31.3% vs. 34.0%, respectively; p = 0.5653) and ARRs (0.50 vs. 0.55, respectively) while persistent to treatment. After adjusting for baseline differences, fingolimod was associated with a 52% reduction in the probability of having a relapse (odds ratio, 0.48; 95% confidence interval [CI], 0.28-0.84; p = 0.0097) and a 50% reduction in ARR (rate ratio, 0.50; 95% CI, 0.34-0.75; p = 0.0006) compared with IFN/GA. LIMITATIONS: Identification of relapses is based on the claims in the database rather than on a clinical assessment. CONCLUSIONS: In a real-world setting, fingolimod was shown to be associated with significantly lower relapse rates than IFN/GA in patients with MS who had a history of relapses.

Cost-minimization analysis of fingolimod compared with natalizumab for the treatment of relapsing-remitting multiple sclerosis in Sweden.

BACKGROUND: Fingolimod and natalizumab have the same European Union licence for the treatment of relapsing multiple sclerosis, and are considered by the Committee for Medicinal Products for Human Use (CHMP) to have broadly similar efficacy. OBJECTIVE: A cost-minimization analysis was performed to compare differences in treatment costs between fingolimod and natalizumab from a societal perspective in Sweden. METHODS: This analysis included costs associated with initiating and following treatment (physician visits and monitoring), continuing therapy (drugs and administration), and lost patient productivity and leisure time. Unit costs (in Swedish krona [SEK]) were based on regional data (median prices for physician visits and monitoring sessions). Natalizumab infusion costs were obtained from the national cost-per-patient database. Drug costs for both therapies were 15,651 SEK/28 days. RESULTS: After 3 years, fingolimod use was associated with savings of 124,823 SEK/patient compared with natalizumab (total cost/patient: 566,718 SEK vs 691,542 SEK). Cost savings with fingolimod were 40,402 SEK/patient after 1 year and 301,730 SEK/patient after 10 years. Treatment with natalizumab was 18% more expensive than fingolimod therapy after 1 year and 23% more expensive after 10 years. LIMITATIONS: Based on the CHMP assessment, it was assumed that fingolimod and natalizumab have similar efficacy. The analysis was conducted for Sweden, and caution is needed in extrapolating the results to other countries. CONCLUSION: Fingolimod is cost-saving compared with natalizumab for the treatment of relapsing-remitting multiple sclerosis in Sweden.

Predictors of costs of care in Alzheimer's disease: a multinational sample of 1222 patients.

BACKGROUND: The costs of care for patients with Alzheimer's disease are correlated with key measures of disease severity. This relationship is important in the economic evaluation of new treatments and is used to translate treatment efficacy into effects on costs through economic modeling. We aimed to identify what measures of disease severity are the most important predictors of societal costs of care and whether their relationship differs across countries. METHODS: Interviews were conducted with 1222 patient and caregiver pairs residing in the community or in residential care settings in Spain, Sweden, United Kingdom, and the United States. Assessments included costs of care (Resource Utilization in Dementia) and key disease severity measures: cognitive function (Mini-Mental State Examination), ability to perform Activities of Daily Living (ADL-ability, Disability Assessment for Dementia [DAD]), and behavioral symptoms (Neuropsychiatry Inventory (NPI)-severity). RESULTS: ADL-ability was the most important predictor of societal costs of care of community-dwelling patients in all countries. A one-point decrease in DAD resulted in a 1.4% increase in costs of care in Spain, United Kingdom, and the United States on average, and a 2% increase in Sweden. This translated into a 45% increase from a standard deviation decrease in DAD on average. NPI-severity and Mini-Mental State Examination were also significant predictors but with lesser effect. Although mean costs of care differed across countries, the important predictors were the same. CONCLUSION: ADL-ability is the most important predictor of societal costs of care in community dwellings irrespective of country and should therefore be central in the economic evaluation of Alzheimer's disease therapies.

Relative importance of patient disease indicators on informal care and caregiver burden in Alzheimer's disease.

BACKGROUND: Cognition, abilities in activities of daily living (ADL), and behavioral disturbances in patients with Alzheimer's disease (AD) all influence the number of hours informal caregivers spend caring for their patients, and the burden caregivers experience. However, the direct effect and relative importance of each disease severity measure remains unclear. METHODS: Cross-sectional interviews were conducted with 1,222 AD patients and primary caregivers in Spain, Sweden, the U.K. and the U.S.A. Assessments included informal care hours, caregiver burden (Zarit Burden Inventory; ZBI), cognition (Mini-mental State Examination; MMSE), ADL-abilities (Disability Assessment for Dementia scale; DAD), and behavioral symptoms (Neuropsychiatric Inventory Questionnaire; NPI-severity). RESULTS: Multivariate analyses of 866 community-dwelling patients revealed that ADL-ability was the strongest predictor of informal care hours (36% decrease in informal care hours per standard deviation (SD) increase in DAD scores). Severity of behavioral disturbances was the strongest predictor of caregiver burden (0.35 SD increase in ZBI score per SD increase in NPI-Q severity score). In addition, the effect of ADL-abilities was, although attenuated, not negligible (0.28 SD increase in ZBI score per SD increase in DAD score). Decreasing cognition (MMSE) was associated with more informal care hours and increased caregiver burden in univariate, but not in adjusted analyses. CONCLUSIONS: For patients residing in community dwellings, the direct influence of patients' cognition on caregiver burden is limited and rather mediated by other disease indicators. Instead, the patients' ADL-abilities are the main predictor of informal care hours, and both ADL-abilities and behavioral disturbances are important predictors of perceived caregiver burden, where the latter has the strongest effect. These results were consistent across Sweden, U.K. and the U.S.A.

Gestational age differences in health and development among young Swedish men born at term.

BACKGROUND: Although increased morbidity and mortality associated with pre-term birth and restricted fetal growth have been extensively studied, relatively little is known about variations in health outcomes among term births, because they are often assumed to be homogeneous. METHODS: We examined variations in height, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), and intellectual performance by gestational age and fetal 'growth' (birth weight for gestational age) among young Swedish men born at term (37-41 weeks of gestation). We also compared the magnitude of associations among 314,642 men from different families and among 72,212 full brothers from 35,215 families to assess whether the associations are explained by familial factors shared by siblings. RESULTS: Gestational age in completed weeks was positively associated with height [0.11 cm, 95% confidence interval (CI): 0.09-0.13] and intellectual performance (0.01, 95% CI: 0.00-0.02) and negatively associated with SBP (-0.28 mmHg, 95% CI: -0.33 to -0.24), after controlling for birth weight, maternal age at the men's birth, parity, family socio-economic position and family structure. The associations with height and SBP were observed also among brothers within families, suggesting that they are not explained by shared family characteristics. However, the positive association between gestational age and intellectual performance was no longer present within families. Birth weight for gestational age (z-score) was positively associated with height, BMI and intellectual performance and negatively associated with SBP. These associations were robust within families. CONCLUSIONS: Among young men born at term, fetal growth and even gestational age are independently associated with adult size, BP and cognitive ability. The extent to which shared family characteristics explain the associations varies across outcomes.

The association between low birth weight and type 2 diabetes: contribution of genetic factors.

BACKGROUND: Low birth weight has been associated with an increased risk of type 2 diabetes in adulthood. Poor fetal nutrition has been suggested to explain this association. Our objective was to determine whether genetic factors contribute to the association between low birth weight and subsequent risk of type 2 diabetes. METHODS: We retrieved information from original birth records on same-sex Swedish twins with known zygosity, born from 1926 to 1958. We used regression models to investigate whether birth weight was associated with risk of type 2 diabetes in the cohort of twins overall, and in case-control analyses within disease-discordant dizygotic and monozygotic twin pairs. RESULTS: Of 18,230 twins, 592 (3.2%) had type 2 diabetes. The rate of type 2 diabetes consistently increased with decreasing birth weight, from 2.4% among twins with birth weights of 3500 g or more to 5.3% among those with birth weights less than 2000 g. In the cohort analysis, in which twins are analyzed as independent individuals, the adjusted odds ratio (95% confidence interval) of type 2 diabetes per 500-g decrease in birth weight was 1.44 (1.28-1.63). When we compared the diseased twin with the healthy cotwin, the corresponding odds ratios were 1.38 (1.02-1.85), among dizygotic twins, and 1.02 (0.63-1.64), among monozygotic twins. CONCLUSIONS: Low birth weight is associated with type 2 diabetes in adulthood. The difference in this association between monozygotic and dizygotic twin pairs suggests that genetic mechanisms play an important role in this association.

Importance of familial factors in associations between offspring birth weight and parental risk of type-2 diabetes.

BACKGROUND: It is hypothesized that associations found between birth weight and subsequent risk of type-2 diabetes are due to inherited genes affecting both fetal growth and metabolism of insulin. METHODS: To study whether there is a familial (shared environmental and genetic) link between birth weight and type-2 diabetes, the authors used a sample of 11,411 Swedish like-sexed twins born from 1926 to 1958 with at least one offspring, to study the association between offspring birth weight for gestational age and parental risk of type-2 diabetes. RESULTS: Decreasing offspring birth weight for gestational age (with 1 SD) was associated with an increased risk of type-2 diabetes among father's [odds ratio (OR)=1.72, 95% confidence interval (CI): 1.33-2.23] and decreased risk among mothers (OR=0.43, 95% CI: 0.30-0.62), independent of grand parental and parental socio-economic status and parental smoking. In paired twin analysis, the association between offspring birth weight and mothers with risk of type-2 diabetes was similar within- and between-twin pairs, whereas father's risk was slightly smaller within than between pairs (OR(Between)=1.90, 95% CI: 1.10-3.28, and OR(Within)=1.71, 95% CI: 1.10-2.67, respectively). CONCLUSIONS: The well-established association between paternal type-2 diabetes and offspring birth weight seems to primarily be due to as yet unidentified non-shared environmental factors. However, familial factors shared within twin pairs may contribute to the association.

Genetic and shared environmental factors do not confound the association between birth weight and hypertension: a study among Swedish twins.

BACKGROUND: Studies have found associations between low birth weight and increased risks of cardiovascular diseases in adulthood. However, these associations could be due to confounding by genetic or socioeconomic factors. METHODS AND RESULTS: We performed a study on Swedish like-sexed twins with known zygosity who were born from 1926 to 1958. First, to obtain an overall effect of birth weight on risk of hypertension, we performed cohort analyses on all twins (n=16,265). Second, to address genetic and shared environmental confounding, we performed a nested co-twin control analysis within 594 dizygotic and 250 monozygotic twin pairs discordant for hypertension. Birth characteristics, including birth weight, were obtained from original birth records. Information from adulthood was collected from a postal questionnaire in 1973 (body mass index, height, smoking, and alcohol use) and from a telephone interview conducted from 1998 to 2002 (hypertension and socioeconomic status). Hypertension was defined as reporting both high blood pressure and treatment with antihypertensive medication. In the cohort analysis, the adjusted odds ratio for hypertension in relation to a 500-g decrease in birth weight was 1.42 (95% confidence interval, 1.25 to 1.61). In the co-twin control analyses, the corresponding odds ratios were 1.34 (95% confidence interval, 1.07 to 1.69) for dizygotic and 1.74 (95% confidence interval, 1.13 to 2.70) for monozygotic twins. CONCLUSIONS: In the largest twin study on the fetal origins of hypertension, we found that decreased birth weight is associated with increased risk of hypertension independently of genetic factors, shared familial environment, and risk factors for hypertension in adulthood, including body mass index.

Risks for low intellectual performance related to being born small for gestational age are modified by gestational age.

OBJECTIVE: We sought to study whether the association between being born small for gestational age and risk for low intellectual performance was modified by gestational age. METHODS: A population-based cohort study was conducted of 352,125 boys who were born between 28 and 43 completed weeks of gestation from 1973 to 1981 in Sweden. Risk for low intellectual performance at military conscription, estimated as odds ratios with 95% confidence intervals was measured. RESULTS: Compared with men who were born preterm (28-36 weeks) and had normal birth weight for gestational age, men who were born preterm and had a very low birth weight for gestational age were not at increased risk for low intellectual performance. In contrast, men who were born preterm with a very short birth length or a very small head circumference for gestational age faced a near doubled risk for low intellectual performance compared with their appropriate peers. Among men who were born at term (37-41 weeks), risk for low intellectual performance was increased among those with very or moderately small birth weight, birth length, or head circumference for gestational age. CONCLUSIONS: During early stages of gestation, growth in length and head circumference may be more important for intellectual development than weight increase. Future studies on size at birth and intellectual performance should consider also including anthropometric measurements other than birth weight.

Birth characteristics and risk of low intellectual performance in early adulthood: are the associations confounded by socioeconomic factors in adolescence or familial effects?

OBJECTIVE: In this study we investigated whether the association between measures of fetal growth restriction and intellectual performance was mediated by socioeconomic or familial factors. METHODS: This was a population-based cohort study of 357,768 Swedish males born as singletons without congenital malformations between 1973 and 1981. The main outcome measure was intellectual performance at military conscription. RESULTS: Compared with men born with appropriate birth weight for gestational age, men born light for gestational age suffered an increased risk of low intellectual performance after adjustment for maternal and socioeconomic factors. The increase in risk of low intellectual performance related to a decrease in birth weight for gestational age was similar between families and within families. Men born short or with a small head circumference for gestational age were also at increased risk of low intellectual performance, both when adjusting for maternal and socioeconomic factors and within families. CONCLUSIONS: We found that all of the studied dimensions of restricted fetal growth are independently associated with increased risks of low intellectual performance and that these associations are only partly mediated by socioeconomic or familial factors.

Risk of high blood pressure among young men increases with the degree of immaturity at birth.

BACKGROUND: Survivors of preterm birth constitute a new generation of young adults, but little is known about their long-term health. We investigated the association between gestational age (GA) and risk of high blood pressure (HBP) in young Swedish men and whether GA modified the risk of HBP; ie, whether HBP was related to being born small for gestational age (SGA). METHODS AND RESULTS: This population-based cohort study included 329 495 Swedish men born in 1973 to 1981 who were conscripted for military service in 1993 to 2001. Multivariate linear- and logistic-regression analyses were performed. Main outcome measures were systolic and diastolic BPs at conscription. Linear-regression analyses showed that systolic BP increased with decreasing GA (regression coefficient -0.31 mm Hg/wk, P<0.001). Systolic and diastolic BPs both increased with decreasing birth weight for GA, but the association with systolic BP was most evident (regression coefficient -0.67 mm Hg per SD score in birth weight for GA, P<0.001). Compared with men born at term (GA, 37 to 41 weeks), the adjusted odd ratios (95% confidence intervals [CIs]) for high systolic BP (> or =140 mm Hg) were as follows: moderately preterm (33 to 36 weeks), 1.25 (1.19 to 1.30); very preterm (29 to 32 weeks), 1.48 (1.30 to 1.68); and extremely preterm (24 to 28 weeks), 1.93 (1.34 to 2.76). Being SGA was associated only with an increased risk of high systolic BP among men born at 33 weeks or later. The risk estimates for high diastolic BP (> or =90 mm Hg) increased with decreasing GA, but the risk reached significance only among men born moderately preterm. CONCLUSIONS: Preterm birth, a common pregnancy complication, is a risk factor for HBP in young men. The risk of high systolic BP associated with birth weight for GA is modified by GA, suggesting that perinatal contributions to BP elevation later in life may be induced by different biological pathways.

Birth characteristics and risk of high systolic blood pressure in early adulthood: socioeconomic factors and familial effects.

BACKGROUND: Although an inverse association between size at birth and blood pressure has been found in several studies, few studies have adjusted for the influence of socioeconomic and familial effects. METHODS: We investigated whether the association between birth weight and systolic blood pressure in young men is confounded by socioeconomic factors in adolescence or familial factors (ie, common genes and shared environment). Our population-based cohort study comprised 330,768 Swedish men born between 1973 and 1981, and conscripted for military service between 1991 and 2000. The analyses of family effects were restricted to 89,856 siblings from the initial cohort. A high systolic blood pressure at conscription was defined as a systolic blood pressure >/=140 mm Hg. Birth weight for gestational age <-2 standard deviation scores was considered "light for gestational age." RESULTS: Compared with men who had normal birth weight for gestational age, men who had been born light for gestational age were at increased risk of high systolic blood pressure (odds ratio = 1.14; 95% confidence interval = 1.07-1.22), even after adjustment for important confounders such as socioeconomic status. The increase in risk of high systolic blood pressure related to 1 standard deviation score decrease in birth weight for gestational age was similar within families (1.08; 1.04-1.12) and between families (1.05; 1.03-1.08). CONCLUSIONS: This study suggests that low birth weight for gestational age slightly increases the risk of high systolic blood pressure, and that the association appears not to be confounded by socioeconomic or familial effects.