Background Several studies have linked low birth weight to adverse levels of cardiovascular risk factors and related diseases. However, information is sparse at a community level in the U.S. general population regarding the effects of low birth weight on the longitudinal trends in cardiovascular risk factor variables measured concurrently from childhood to adolescence.
Background
Several studies have linked low birth weight to adverse levels of cardiovascular risk factors and related diseases. However, information is sparse at a community level in the U.S. general population regarding the effects of low birth weight on the longitudinal trends in cardiovascular risk factor variables measured concurrently from childhood to adolescence.Methods Longitudinal analysis was performed retrospectively on data collected from the Bogalusa Heart Study cohort (n = 1141; 57% white, 43% black) followed from childhood to adolescence by repeated surveys between 1973 and 1996. Subjects were categorized into low birth weight (below the race-specific 10 th  percentile; n = 123) and control (between race-specific 50–75 th  percentile; n = 296) groups.
Methods
Longitudinal analysis was performed retrospectively on data collected from the Bogalusa Heart Study cohort (n = 1141; 57% white, 43% black) followed from childhood to adolescence by repeated surveys between 1973 and 1996. Subjects were categorized into low birth weight (below the race-specific 10 th  percentile; n = 123) and control (between race-specific 50–75 th  percentile; n = 296) groups.Results Low birth weight group vs control group had lower mean HDL cholesterol (p = 0.05) and higher LDL cholesterol (p = 0.05) during childhood (ages 4–11 years); higher glucose (p = 0.02) during adolescence. Yearly rates of change from childhood to adolescence in systolic blood pressure (p = 0.02), LDL cholesterol (p = 0.05), and glucose (p = 0.07) were faster, and body mass index (p = 0.03) slower among the low birth weight group. In a multivariate analysis, low birth weight was related independently and adversely to longitudinal trends in systolic blood pressure (p = 0.004), triglycerides (p = 0.03), and glucose (p = 0.07), regardless of race or gender. These adverse associations became amplified with age.
Results
Low birth weight group vs control group had lower mean HDL cholesterol (p = 0.05) and higher LDL cholesterol (p = 0.05) during childhood (ages 4–11 years); higher glucose (p = 0.02) during adolescence. Yearly rates of change from childhood to adolescence in systolic blood pressure (p = 0.02), LDL cholesterol (p = 0.05), and glucose (p = 0.07) were faster, and body mass index (p = 0.03) slower among the low birth weight group. In a multivariate analysis, low birth weight was related independently and adversely to longitudinal trends in systolic blood pressure (p = 0.004), triglycerides (p = 0.03), and glucose (p = 0.07), regardless of race or gender. These adverse associations became amplified with age.Conclusions Low birth weight is characterized by adverse developmental trends in metabolic and hemodynamic variables during childhood and adolescence; and thus, it may be an early risk factor in this regard.
Conclusions
Low birth weight is characterized by adverse developmental trends in metabolic and hemodynamic variables during childhood and adolescence; and thus, it may be an early risk factor in this regard.

Background The growth of a fetus in an undernourished intrauterine environment is considered to result in adaptive fetal programming or metabolic imprinting with pathophysiologic consequences later in life [ 1 - 4 ]. It is contended that low birth weight at term (<2500 g), a surrogate for impaired gestational environment, is uncommon in industrialized societies, and deprivations that existed before the second world war no longer apply to pregnancies at present [ 5 , 6 ]. In reality, the United States birth data for year 2002 show a prevalence of 7.8% low birth weight, with blacks showing almost twice the rate of whites [ 7 ]. Studies world-wide, regardless of socio-economic background, have linked low birth weight to increased risk of insulin resistance, dyslipidemia, hypertension, coronary heart disease, and type 2 diabetes [ 8 - 13 ], although some studies have found a weak or no associations in this regard [ 5 , 14 - 16 ]. Several studies including our own have examined the association between low birth weight and selected cardiovascular risk factor variables in childhood and adolescence [ 17 - 27 ]. However, information is scant on data linking low birth weight to longitudinal changes of cardiovascular risk factor variables measured simultaneously and serially from childhood to adolescence. As part of the Bogalusa Heart Study, a biracial (black-white) community-based investigation of evolution of cardiovascular risk since childhood [ 28 ], the present analysis examines the relationship between low birth weight and the longitudinal trends of adiposity, blood pressure, lipids and lipoproteins, and measures of glucose homeostasis from childhood to adolescence.
Background
The growth of a fetus in an undernourished intrauterine environment is considered to result in adaptive fetal programming or metabolic imprinting with pathophysiologic consequences later in life [ 1 - 4 ]. It is contended that low birth weight at term (<2500 g), a surrogate for impaired gestational environment, is uncommon in industrialized societies, and deprivations that existed before the second world war no longer apply to pregnancies at present [ 5 , 6 ]. In reality, the United States birth data for year 2002 show a prevalence of 7.8% low birth weight, with blacks showing almost twice the rate of whites [ 7 ]. Studies world-wide, regardless of socio-economic background, have linked low birth weight to increased risk of insulin resistance, dyslipidemia, hypertension, coronary heart disease, and type 2 diabetes [ 8 - 13 ], although some studies have found a weak or no associations in this regard [ 5 , 14 - 16 ].Several studies including our own have examined the association between low birth weight and selected cardiovascular risk factor variables in childhood and adolescence [ 17 - 27 ]. However, information is scant on data linking low birth weight to longitudinal changes of cardiovascular risk factor variables measured simultaneously and serially from childhood to adolescence. As part of the Bogalusa Heart Study, a biracial (black-white) community-based investigation of evolution of cardiovascular risk since childhood [ 28 ], the present analysis examines the relationship between low birth weight and the longitudinal trends of adiposity, blood pressure, lipids and lipoproteins, and measures of glucose homeostasis from childhood to adolescence.Methods Study cohorts Between 1973 and 1996, 7 cross-sectional surveys of children and adolescents were conducted in the community (65% white, 35% black) of Bogalusa, LA. This panel design, based on repeated cross-sectional examinations performed every 3 to 4 years, resulted in serial observations required for the longitudinal analysis. For the present report, two sets of data were merged as described previously [ 21 ]: 1) singleton new born cohort participants (n = 233) whose weights were measured at birth as part of the initial examination during 1973–1974; and 2) singletons (n = 1213) aged 7–11 years who participated in 1987–1988 cross-sectional survey and whose birth weight records were obtained from the Office of Vital Statistics in New Orleans in 1991. Of those with birth weight data (n = 1436), 1329 subjects participated in 2 to 7 surveys of children and adolescents. Exclusion of those with missing data (n = 170), congenital heart disease (n = 11), and diabetes (n = 7) resulted in 1141 eligible subjects (57% white, 47% female). Low birth weight and control groups were selected from the eligible cohort, according to birth weight percentile cut points [ 29 ]. Subjects (n = 123) who had birth weight below the race-specific 10 th  percentile (whites: <2749 g; blacks: <2438 g) were categorized as low birth weight group; those (n = 296) in the upper normal range of 50–75 th  percentile (whites: 3402 – 3770 g; blacks: 3133 g – 3487 g) as control group. Birth weights above the 75 th  percentile were not included in the control group because of the u-shaped associations between birth weight and risk factors or disease [ 3 , 30 ]. Race-specific percentile, rather than World Health Organization (WHO) criterion for low birth weight (<2500 g) was used to define low birth weight because of black-white differences in birth weight distribution [ 31 , 32 ]. General examination Identical protocols were used by trained examiners across all surveys [ 33 ]. Subjects were instructed to fast for 12 hours prior to screening, and compliance was determined by interview on the morning of examination. Anthropometric and blood pressure measurements were made in replicate and mean values were used. Height and weight were measured 2 times; subscapular skinfold thickness 3 times. Body mass index (BMI) calculated as weight in kg divided by the square of the height in meters was used as a measure of overall adiposity; subscapular skinfold for truncal fatness. The reproducibility in terms of intraclass (intra-observer) correlation coefficient was greater than 0.99 for weight and height, and greater than 0.97 for subscapular skinfold. Blood pressure levels were measured in 6 replicates by 2 randomly assigned nurses on the right arm of subjects in a relaxed, sitting position. Systolic and diastolic blood pressures were recorded at the first, fourth, and fifth Korotkoff phases using mercury sphygmomanometer. For this analysis fourth phase was used for diastolic blood pressure because in our experience the fourth phase is more reliably measured in children and more predictive of adult hypertension [ 34 ]. Laboratory analyses From 1973 to 1986 cholesterol and triglyceride levels in serum were measured using chemical procedures on Technicon Autoanalyzer II (Technician Instrument Corp., Tarrytown, NY). Since then these measurements were done using enzymatic procedures on Abbott VP instrument (Abbott laboratories, North Chicago, IL). Serum lipoprotein cholesterols were analyzed by a combination of heparin-calcium precipitation and agar-agarose gel electrophoresis procedures [ 35 ]. Both chemical and enzymatic procedures met the performance requirement of the Lipid Standardization Program of the Centers for Disease Control and Prevention, Atlanta, GA. The laboratory has been monitored for precision and accuracy by the agency's surveillance program since 1973. For example, the average bias in levels of total cholesterol on CDC control samples ranged from -0.1 to -1.6 mg/dL between different cross-sectional surveys, with no consistent pattern over time within or between surveys. The intraclass correlation coefficients between the blind duplicate (10% random sample) values ranged from 0.87 to 0.99 for total cholesterol; 0.88 to 0.99 for triglycerides; 0.86 to 0.98 for LDL cholesterol; and 0.86 to 0.98 for HDL cholesterol. Plasma immunoreactive insulin levels were measured by a commercial radioimmunoassay kit (Phadebas, Pharmacia Diagnostics, Piscataway, NJ). Plasma glucose was measured by a glucose oxidase method either using a Beckman glucose analyzer (Beckman Instruments, Fullerton, CA) or as part of a multichemistry (SMA20) profile. The intraclass correlation coefficient between blind duplicate values ranged from 0.94 to 0.98 for insulin and 0.86 to 0.98 for glucose. An index of insulin resistance was calculated according to the homeostasis assessment model formula [ 36 ]: HOMA-IR=fasting insulin (μu/mL) × fasting glucose (mmol/L) ÷ 22.5. Statistical analyses For test of significance glucose and insulin were logarithmically transformed to approach normality. The average of multiple measurements for subjects within age groups 4 to 11 and 12 to 18 years corresponding to childhood and adolescence periods was used to calculate mean levels of risk variables by birth weight status and age groups. Mean levels of risk variables within each age group were compared between low birth weight and control group by a general linear model, adjusting for age, race, and gender. The longitudinal rates of change in risk variables was assessed by the generalized estimation equation (GEE) method [ 37 ] with age as predictor, adjusting for race and gender. Independent association of low birth weight with longitudinal trends of risk variables from childhood to adolescence was assessed by multivariate analysis (GEE). The model included birth weight (low vs control) and risk variables as applicable along with age, age 2 , race and gender and their interaction with birth weight (low vs control). A backward stepwise method was used to remove nonsignificant terms.
Methods
Study cohorts Between 1973 and 1996, 7 cross-sectional surveys of children and adolescents were conducted in the community (65% white, 35% black) of Bogalusa, LA. This panel design, based on repeated cross-sectional examinations performed every 3 to 4 years, resulted in serial observations required for the longitudinal analysis. For the present report, two sets of data were merged as described previously [ 21 ]: 1) singleton new born cohort participants (n = 233) whose weights were measured at birth as part of the initial examination during 1973–1974; and 2) singletons (n = 1213) aged 7–11 years who participated in 1987–1988 cross-sectional survey and whose birth weight records were obtained from the Office of Vital Statistics in New Orleans in 1991. Of those with birth weight data (n = 1436), 1329 subjects participated in 2 to 7 surveys of children and adolescents. Exclusion of those with missing data (n = 170), congenital heart disease (n = 11), and diabetes (n = 7) resulted in 1141 eligible subjects (57% white, 47% female). Low birth weight and control groups were selected from the eligible cohort, according to birth weight percentile cut points [ 29 ]. Subjects (n = 123) who had birth weight below the race-specific 10 th  percentile (whites: <2749 g; blacks: <2438 g) were categorized as low birth weight group; those (n = 296) in the upper normal range of 50–75 th  percentile (whites: 3402 – 3770 g; blacks: 3133 g – 3487 g) as control group. Birth weights above the 75 th  percentile were not included in the control group because of the u-shaped associations between birth weight and risk factors or disease [ 3 , 30 ]. Race-specific percentile, rather than World Health Organization (WHO) criterion for low birth weight (<2500 g) was used to define low birth weight because of black-white differences in birth weight distribution [ 31 , 32 ].
Study cohorts
Between 1973 and 1996, 7 cross-sectional surveys of children and adolescents were conducted in the community (65% white, 35% black) of Bogalusa, LA. This panel design, based on repeated cross-sectional examinations performed every 3 to 4 years, resulted in serial observations required for the longitudinal analysis. For the present report, two sets of data were merged as described previously [ 21 ]: 1) singleton new born cohort participants (n = 233) whose weights were measured at birth as part of the initial examination during 1973–1974; and 2) singletons (n = 1213) aged 7–11 years who participated in 1987–1988 cross-sectional survey and whose birth weight records were obtained from the Office of Vital Statistics in New Orleans in 1991. Of those with birth weight data (n = 1436), 1329 subjects participated in 2 to 7 surveys of children and adolescents. Exclusion of those with missing data (n = 170), congenital heart disease (n = 11), and diabetes (n = 7) resulted in 1141 eligible subjects (57% white, 47% female).Low birth weight and control groups were selected from the eligible cohort, according to birth weight percentile cut points [ 29 ]. Subjects (n = 123) who had birth weight below the race-specific 10 th  percentile (whites: <2749 g; blacks: <2438 g) were categorized as low birth weight group; those (n = 296) in the upper normal range of 50–75 th  percentile (whites: 3402 – 3770 g; blacks: 3133 g – 3487 g) as control group. Birth weights above the 75 th  percentile were not included in the control group because of the u-shaped associations between birth weight and risk factors or disease [ 3 , 30 ]. Race-specific percentile, rather than World Health Organization (WHO) criterion for low birth weight (<2500 g) was used to define low birth weight because of black-white differences in birth weight distribution [ 31 , 32 ].General examination Identical protocols were used by trained examiners across all surveys [ 33 ]. Subjects were instructed to fast for 12 hours prior to screening, and compliance was determined by interview on the morning of examination. Anthropometric and blood pressure measurements were made in replicate and mean values were used. Height and weight were measured 2 times; subscapular skinfold thickness 3 times. Body mass index (BMI) calculated as weight in kg divided by the square of the height in meters was used as a measure of overall adiposity; subscapular skinfold for truncal fatness. The reproducibility in terms of intraclass (intra-observer) correlation coefficient was greater than 0.99 for weight and height, and greater than 0.97 for subscapular skinfold. Blood pressure levels were measured in 6 replicates by 2 randomly assigned nurses on the right arm of subjects in a relaxed, sitting position. Systolic and diastolic blood pressures were recorded at the first, fourth, and fifth Korotkoff phases using mercury sphygmomanometer. For this analysis fourth phase was used for diastolic blood pressure because in our experience the fourth phase is more reliably measured in children and more predictive of adult hypertension [ 34 ].
General examination
Identical protocols were used by trained examiners across all surveys [ 33 ]. Subjects were instructed to fast for 12 hours prior to screening, and compliance was determined by interview on the morning of examination. Anthropometric and blood pressure measurements were made in replicate and mean values were used.Height and weight were measured 2 times; subscapular skinfold thickness 3 times. Body mass index (BMI) calculated as weight in kg divided by the square of the height in meters was used as a measure of overall adiposity; subscapular skinfold for truncal fatness. The reproducibility in terms of intraclass (intra-observer) correlation coefficient was greater than 0.99 for weight and height, and greater than 0.97 for subscapular skinfold.Blood pressure levels were measured in 6 replicates by 2 randomly assigned nurses on the right arm of subjects in a relaxed, sitting position. Systolic and diastolic blood pressures were recorded at the first, fourth, and fifth Korotkoff phases using mercury sphygmomanometer. For this analysis fourth phase was used for diastolic blood pressure because in our experience the fourth phase is more reliably measured in children and more predictive of adult hypertension [ 34 ].Laboratory analyses From 1973 to 1986 cholesterol and triglyceride levels in serum were measured using chemical procedures on Technicon Autoanalyzer II (Technician Instrument Corp., Tarrytown, NY). Since then these measurements were done using enzymatic procedures on Abbott VP instrument (Abbott laboratories, North Chicago, IL). Serum lipoprotein cholesterols were analyzed by a combination of heparin-calcium precipitation and agar-agarose gel electrophoresis procedures [ 35 ]. Both chemical and enzymatic procedures met the performance requirement of the Lipid Standardization Program of the Centers for Disease Control and Prevention, Atlanta, GA. The laboratory has been monitored for precision and accuracy by the agency's surveillance program since 1973. For example, the average bias in levels of total cholesterol on CDC control samples ranged from -0.1 to -1.6 mg/dL between different cross-sectional surveys, with no consistent pattern over time within or between surveys. The intraclass correlation coefficients between the blind duplicate (10% random sample) values ranged from 0.87 to 0.99 for total cholesterol; 0.88 to 0.99 for triglycerides; 0.86 to 0.98 for LDL cholesterol; and 0.86 to 0.98 for HDL cholesterol. Plasma immunoreactive insulin levels were measured by a commercial radioimmunoassay kit (Phadebas, Pharmacia Diagnostics, Piscataway, NJ). Plasma glucose was measured by a glucose oxidase method either using a Beckman glucose analyzer (Beckman Instruments, Fullerton, CA) or as part of a multichemistry (SMA20) profile. The intraclass correlation coefficient between blind duplicate values ranged from 0.94 to 0.98 for insulin and 0.86 to 0.98 for glucose. An index of insulin resistance was calculated according to the homeostasis assessment model formula [ 36 ]: HOMA-IR=fasting insulin (μu/mL) × fasting glucose (mmol/L) ÷ 22.5.
Laboratory analyses
From 1973 to 1986 cholesterol and triglyceride levels in serum were measured using chemical procedures on Technicon Autoanalyzer II (Technician Instrument Corp., Tarrytown, NY). Since then these measurements were done using enzymatic procedures on Abbott VP instrument (Abbott laboratories, North Chicago, IL). Serum lipoprotein cholesterols were analyzed by a combination of heparin-calcium precipitation and agar-agarose gel electrophoresis procedures [ 35 ]. Both chemical and enzymatic procedures met the performance requirement of the Lipid Standardization Program of the Centers for Disease Control and Prevention, Atlanta, GA. The laboratory has been monitored for precision and accuracy by the agency's surveillance program since 1973. For example, the average bias in levels of total cholesterol on CDC control samples ranged from -0.1 to -1.6 mg/dL between different cross-sectional surveys, with no consistent pattern over time within or between surveys. The intraclass correlation coefficients between the blind duplicate (10% random sample) values ranged from 0.87 to 0.99 for total cholesterol; 0.88 to 0.99 for triglycerides; 0.86 to 0.98 for LDL cholesterol; and 0.86 to 0.98 for HDL cholesterol.Plasma immunoreactive insulin levels were measured by a commercial radioimmunoassay kit (Phadebas, Pharmacia Diagnostics, Piscataway, NJ). Plasma glucose was measured by a glucose oxidase method either using a Beckman glucose analyzer (Beckman Instruments, Fullerton, CA) or as part of a multichemistry (SMA20) profile. The intraclass correlation coefficient between blind duplicate values ranged from 0.94 to 0.98 for insulin and 0.86 to 0.98 for glucose. An index of insulin resistance was calculated according to the homeostasis assessment model formula [ 36 ]: HOMA-IR=fasting insulin (μu/mL) × fasting glucose (mmol/L) ÷ 22.5.Statistical analyses For test of significance glucose and insulin were logarithmically transformed to approach normality. The average of multiple measurements for subjects within age groups 4 to 11 and 12 to 18 years corresponding to childhood and adolescence periods was used to calculate mean levels of risk variables by birth weight status and age groups. Mean levels of risk variables within each age group were compared between low birth weight and control group by a general linear model, adjusting for age, race, and gender. The longitudinal rates of change in risk variables was assessed by the generalized estimation equation (GEE) method [ 37 ] with age as predictor, adjusting for race and gender. Independent association of low birth weight with longitudinal trends of risk variables from childhood to adolescence was assessed by multivariate analysis (GEE). The model included birth weight (low vs control) and risk variables as applicable along with age, age 2 , race and gender and their interaction with birth weight (low vs control). A backward stepwise method was used to remove nonsignificant terms.
Statistical analyses
For test of significance glucose and insulin were logarithmically transformed to approach normality. The average of multiple measurements for subjects within age groups 4 to 11 and 12 to 18 years corresponding to childhood and adolescence periods was used to calculate mean levels of risk variables by birth weight status and age groups. Mean levels of risk variables within each age group were compared between low birth weight and control group by a general linear model, adjusting for age, race, and gender. The longitudinal rates of change in risk variables was assessed by the generalized estimation equation (GEE) method [ 37 ] with age as predictor, adjusting for race and gender. Independent association of low birth weight with longitudinal trends of risk variables from childhood to adolescence was assessed by multivariate analysis (GEE). The model included birth weight (low vs control) and risk variables as applicable along with age, age 2 , race and gender and their interaction with birth weight (low vs control). A backward stepwise method was used to remove nonsignificant terms.Results Mean levels of cardiovascular risk variables during childhood (ages 4–11 years) and adolescence (ages 12–18 years) periods are shown in table  1  by birth weight groups. Of the risk variables adjusted for age, race, and gender, levels of HDL cholesterol were significantly lower and LDL cholesterol higher among low birth weight group vs control group during childhood. During adolescence, only glucose levels were significantly higher among low birth weight group vs control group. Table 1 Levels (mean ± SD) of risk variables during childhood and adolescence by birth weight. The Bogalusa Heart Study Variable Childhood (4–11 years) Adolescence (12–18 years) Low Birth Weight Control Low Birth Weight Control BMI (kg/m 2 ) 16.7 ± 2.6 17.5 ± 2.9 21.6 ± 5.2 22.7 ± 5.0 Subsc. Skinfold (mm) 8.2 ± 5.1 8.3 ± 6.4 15.9 ± 10.0 16.0 ± 10.7 Syst. BP (mm Hg) 96.4 ± 9.0 98.6 ± 8.1 108.8 ± 9.1 105.2 ± 8.7 Diast. BP (mm Hg) 57.2 ± 10.2 58.7 ± 7.9 66.1 ± 8.0 66.4 ± 7.4 Triglycerides (mg/dL) 62.6 ± 23.2 52.8 ± 20.3 87.1 ± 29.0 83.2 ± 35.3 HDL cholesterol (mg/dL) 44.3 ± 22.6 a 54.7 ± 17.4 49.9 ± 12.8 51.2 ± 11.5 LDL cholesterol (mg/dL) 76.0 ± 35.4  a 68.6 ± 37.6 99.5 ± 24.7 98.4 ± 24.3 Glucose (mg/dL) 79.7 ± 8.1 80.9 ± 9.7 85.4 ± 8.2 b 81.6 ± 7.4 Insulin (μu/mL) 8.5 ± 5.7 7.4 ± 4.6 14.8 ± 7.5 13.2 ± 8.6 HOMA-IR 1.7 ± 1.2 1.6 ± 1.0 3.0 ± 2.4 2.7 ± 2.0 Difference between groups (adjusted for age, race, and gender), a: p = 0.05; b: p = 0.02 HOMA-IR: homeostasis model assessment index of insulin resistance Longitudinal rates of change in cardiovascular risk variables from childhood to adolescence, adjusted for race and gender, are presented in table  2  by birth weight groups. The rate of increase in BMI was significantly lower in low birth weight group compared with control group, while the rate of increase in subscapular skinfold remained similar between the groups. With respect to blood pressure, the rate of increase in systolic blood pressure was significantly higher in low birth weight group than control group. Of the measures of glucose homeostasis, rate of increase of glucose was marginally significant in low birth weight group vs control group. Low birth weight was associated with significantly higher rate of increase in LDL cholesterol; and no significant trends in HDL cholesterol and triglycerides. Table 2 Rates of change in risk variables from childhood to adolescence by birth weight. The Bogalusa Heart Study Variable Low Birth Weight Control p-value BMI (kg/m 2 /y) 0.60 † 0.71 0.03 Subsc. Skinfold (mm/y) 0.91 1.12 0.27 Syst. BP (mmHg/y) 1.70 1.30 0.02 Diast. BP (mm Hg/y) 1.21 1.02 0.26 Triglycerides (mg/dL/y) 2.28 2.92 0.80 HDL cholesterol (mg/dL/y) -0.53 -0.91 0.24 LDL cholesterol (mg/dL/y) 0.80 0.64 0.05 Glucose (mg/dL/y) 0.50 0.11 0.07 Insulin (μu/mL/y) 0.79 0.67 0.70 HOMA-IR 0.18 0.14 0.44 † Regression slope with respect to age in years (y) adjusted for race and gender (generalized equation estimation method). HOMA-IR: homeostatis model assessment index of insulin resistance. In a multivariate analysis, low birth weight was retained as an independent predictor variable for adverse longitudinal trends in systolic blood pressure, triglycerides, and glucose (marginal) from childhood to adolescence, regardless of race or gender (table  3 ). Further, there was a significant interaction between low birth weight and age in this regard, denoting that these variables increased to a greater extent in the low birth weight group than in the control group as individuals became older. An analysis of this data set using the WHO criterion for low birth weight (<2500 g) showed that only 36 subjects were reclassified as having normal birth weight, and the results were essentially the same (data not shown). Table 3 Independent association of low birth weight with longitudinal trends of systolic blood pressure, triglycerides and glucose from childhood to adolescence Independent Variables Retained Syst. BP Triglycerides Glucose β † p-value β p-value β p-value Birth Weight (low vs control) 3.84 0.02 48.6 0.08 15.20 0.07 Gender (male vs female) -- -- -- -- 4.31 <0.001 Age 0.39 0.40 12.21 0.01 6.60 <0.001 Age 2 0.06 0.002 -0.44 0.04 -0.31 <0.001 Insulin 0.11 0.03 1.16 <0.001 0.22 0.02 BMI 0.34 <0.001 -- -- -- -- Birth weight × age 0.45 0.004 12.71 0.03 0.10 0.07 Birth weight × age 2 -- -- 0.55 0.02 2.65 0.10 † GEE regression coefficient. The model included birth weight (low vs control) along with age, age 2 , race, and gender, and their interaction with birth weight; and risk variable as applicable.
Results
Mean levels of cardiovascular risk variables during childhood (ages 4–11 years) and adolescence (ages 12–18 years) periods are shown in table  1  by birth weight groups. Of the risk variables adjusted for age, race, and gender, levels of HDL cholesterol were significantly lower and LDL cholesterol higher among low birth weight group vs control group during childhood. During adolescence, only glucose levels were significantly higher among low birth weight group vs control group.Levels (mean ± SD) of risk variables during childhood and adolescence by birth weight. The Bogalusa Heart StudyDifference between groups (adjusted for age, race, and gender), a: p = 0.05; b: p = 0.02HOMA-IR: homeostasis model assessment index of insulin resistanceLongitudinal rates of change in cardiovascular risk variables from childhood to adolescence, adjusted for race and gender, are presented in table  2  by birth weight groups. The rate of increase in BMI was significantly lower in low birth weight group compared with control group, while the rate of increase in subscapular skinfold remained similar between the groups. With respect to blood pressure, the rate of increase in systolic blood pressure was significantly higher in low birth weight group than control group. Of the measures of glucose homeostasis, rate of increase of glucose was marginally significant in low birth weight group vs control group. Low birth weight was associated with significantly higher rate of increase in LDL cholesterol; and no significant trends in HDL cholesterol and triglycerides.Rates of change in risk variables from childhood to adolescence by birth weight. The Bogalusa Heart Study† Regression slope with respect to age in years (y) adjusted for race and gender (generalized equation estimation method).HOMA-IR: homeostatis model assessment index of insulin resistance.In a multivariate analysis, low birth weight was retained as an independent predictor variable for adverse longitudinal trends in systolic blood pressure, triglycerides, and glucose (marginal) from childhood to adolescence, regardless of race or gender (table  3 ). Further, there was a significant interaction between low birth weight and age in this regard, denoting that these variables increased to a greater extent in the low birth weight group than in the control group as individuals became older. An analysis of this data set using the WHO criterion for low birth weight (<2500 g) showed that only 36 subjects were reclassified as having normal birth weight, and the results were essentially the same (data not shown).Independent association of low birth weight with longitudinal trends of systolic blood pressure, triglycerides and glucose from childhood to adolescence† GEE regression coefficient. The model included birth weight (low vs control) along with age, age 2 , race, and gender, and their interaction with birth weight; and risk variable as applicable.Discussion Information is sparse at a community level in the U.S. general population regarding the effects of low birth weight on the longitudinal trends in C-V risk factor variables measured serially and concurrently from childhood to adolescence. The present community-based study demonstrates the adverse effects of low birth weight on the longitudinal (developmental) trends in systolic blood pressure, triglycerides, and glucose during childhood and adolescence, regardless of race or gender. These observations are in accord with the emerging evidence supporting the concept of intrauterine imprinting and its pathophysiologic consequences enunciated by the fetal origin or thrifty phenotype hypothesis [ 3 ]. Many, but not all, previous studies in children and adolescents have found adverse associations between birth weight and levels of cardiovascular risk factor variables [ 16 - 27 ]. In this study, the magnitude of differences in mean levels of cardiovascular risk factor variables between low birth weight and control groups during childhood and adolescence periods were small and nonsignificant for most of the study variables, except for the adverse levels HDL cholesterol and LDL cholesterol in childhood and glucose in adolescence among the low birth weight group. However, in a multivariate analysis of the serial data, the independent adverse effects of low birth weight on the longitudinal trends of systolic blood pressure, triglycerides, and glucose were discernable in the study cohort. Of note, the observed adverse trends associated with low birth weight vs control group were influenced by age in that the differences became greater in magnitude as the children got older. Earlier studies have reported that the inverse associations between birth weight and levels of cardiovascular risk factor variables became stronger with increasing age [ 26 , 38 ]. Whether the potentiating effect of increasing age on low birth weight – risk variable relationship reflects the interaction between fetal programming related to intrauterine malnutrition and the increasing burden with age of unhealthy life-style behaviors including overnutrition and sedentary life style is not clear. In this context, it should be noted that although the rate of yearly increase in BMI, which also includes muscle mass, was significantly lower in low birth weight group, the rate of increase in subscapular skinfold, a measure of truncal fat, remained similar to that of control group. This suggests a gaining of truncal fat, in relative term, over muscle mass in the low birth weight group. Although observational studies like the present one can not establish causality, several putative mechanisms link low birth weight to adverse trends in risk factor variables. It has been suggested that insulin resistance may be one mechanism by which intrauterine events may program disease risk [ 39 ]. Undernutrition in utero is known to cause permanent impairment in growth, structure and function of muscle [ 39 , 40 ], fat [ 41 , 42 ], endocrine pancreas [ 2 , 43 ], liver [ 30 ], renal nephrons [ 44 , 45 ] and vasculature [ 46 ] due to biologic programming, resulting in insulin resistance/glucose intolerance, hypertension, and dyslipidemia. Further, it has been suggested that intrauterine programming of the hypothalamic-pituitary-adrenal axis may be a functional mechanism underlying the link between low birth weight and above disorders [ 47 ], known as components of insulin resistance or metabolic syndrome [ 48 ]. This study has certain limitations. The lack of information on the duration of gestation precluded us from adjusting the birth weight for gestational age, a potential confounder. However, earlier studies have found that adverse effects of low birth weight on cardiovascular risk factor variables were independent of gestation period [ 10 , 17 , 49 ]. Further, it has been pointed out that inclusion of preterm births could actually underestimate these associations [ 28 ]. This study also lacks measurements of glucose tolerance and insulin action and secretion used in etiologic studies. Instead, we used the glucose homeostasis measures that are relatively easily measured and applicable at a population level.
Discussion
Information is sparse at a community level in the U.S. general population regarding the effects of low birth weight on the longitudinal trends in C-V risk factor variables measured serially and concurrently from childhood to adolescence. The present community-based study demonstrates the adverse effects of low birth weight on the longitudinal (developmental) trends in systolic blood pressure, triglycerides, and glucose during childhood and adolescence, regardless of race or gender. These observations are in accord with the emerging evidence supporting the concept of intrauterine imprinting and its pathophysiologic consequences enunciated by the fetal origin or thrifty phenotype hypothesis [ 3 ].Many, but not all, previous studies in children and adolescents have found adverse associations between birth weight and levels of cardiovascular risk factor variables [ 16 - 27 ]. In this study, the magnitude of differences in mean levels of cardiovascular risk factor variables between low birth weight and control groups during childhood and adolescence periods were small and nonsignificant for most of the study variables, except for the adverse levels HDL cholesterol and LDL cholesterol in childhood and glucose in adolescence among the low birth weight group. However, in a multivariate analysis of the serial data, the independent adverse effects of low birth weight on the longitudinal trends of systolic blood pressure, triglycerides, and glucose were discernable in the study cohort. Of note, the observed adverse trends associated with low birth weight vs control group were influenced by age in that the differences became greater in magnitude as the children got older. Earlier studies have reported that the inverse associations between birth weight and levels of cardiovascular risk factor variables became stronger with increasing age [ 26 , 38 ]. Whether the potentiating effect of increasing age on low birth weight – risk variable relationship reflects the interaction between fetal programming related to intrauterine malnutrition and the increasing burden with age of unhealthy life-style behaviors including overnutrition and sedentary life style is not clear. In this context, it should be noted that although the rate of yearly increase in BMI, which also includes muscle mass, was significantly lower in low birth weight group, the rate of increase in subscapular skinfold, a measure of truncal fat, remained similar to that of control group. This suggests a gaining of truncal fat, in relative term, over muscle mass in the low birth weight group.Although observational studies like the present one can not establish causality, several putative mechanisms link low birth weight to adverse trends in risk factor variables. It has been suggested that insulin resistance may be one mechanism by which intrauterine events may program disease risk [ 39 ]. Undernutrition in utero is known to cause permanent impairment in growth, structure and function of muscle [ 39 , 40 ], fat [ 41 , 42 ], endocrine pancreas [ 2 , 43 ], liver [ 30 ], renal nephrons [ 44 , 45 ] and vasculature [ 46 ] due to biologic programming, resulting in insulin resistance/glucose intolerance, hypertension, and dyslipidemia. Further, it has been suggested that intrauterine programming of the hypothalamic-pituitary-adrenal axis may be a functional mechanism underlying the link between low birth weight and above disorders [ 47 ], known as components of insulin resistance or metabolic syndrome [ 48 ].This study has certain limitations. The lack of information on the duration of gestation precluded us from adjusting the birth weight for gestational age, a potential confounder. However, earlier studies have found that adverse effects of low birth weight on cardiovascular risk factor variables were independent of gestation period [ 10 , 17 , 49 ]. Further, it has been pointed out that inclusion of preterm births could actually underestimate these associations [ 28 ]. This study also lacks measurements of glucose tolerance and insulin action and secretion used in etiologic studies. Instead, we used the glucose homeostasis measures that are relatively easily measured and applicable at a population level.Conclusions Low birth is characterized by adverse developmental trends in metabolic and hemodynamic variables during childhood and adolescence, especially as the children get older. These observations in conjunction with earlier findings support the view that low birth weight, albeit a crude marker of prenatal growth and physiological environment, is a potential early risk factor for the emergence of metabolic and hemodynamic disorders and related diseases [ 1 , 50 ].
Conclusions
Low birth is characterized by adverse developmental trends in metabolic and hemodynamic variables during childhood and adolescence, especially as the children get older. These observations in conjunction with earlier findings support the view that low birth weight, albeit a crude marker of prenatal growth and physiological environment, is a potential early risk factor for the emergence of metabolic and hemodynamic disorders and related diseases [ 1 , 50 ].Abbreviations BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density lipoprotein
Abbreviations
BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density lipoproteinCompeting interests The author(s) declare that they have no competing interests.
Competing interests
The author(s) declare that they have no competing interests.Authors' contributions MGF participated in study design, data analysis and manuscript preparation. SRS and GSB contributed to study concept and design, data collection, acquisition of funding and manuscript preparation. JX was involved in measurements of laboratory variables. All authors read and approved the final manuscript.
Authors' contributions
MGF participated in study design, data analysis and manuscript preparation. SRS and GSB contributed to study concept and design, data collection, acquisition of funding and manuscript preparation. JX was involved in measurements of laboratory variables. All authors read and approved the final manuscript.Pre-publication history The pre-publication history for this paper can be accessed here:
Pre-publication history
The pre-publication history for this paper can be accessed here:


Advances in neuroscience and biomedical engineering deeply affect the clinical practice of physical medicine & rehabilitation. New research findings and engineering tools are continuously made available that have the potential of dramatically enhancing the ability of clinicians to design effective rehabilitation interventions. This quickly evolving research field is difficult to track because related literature appears in a wide range of scientific journals. There is a need for a scientific journal that offers to its readership a forum at the intersection of neuroscience, biomedical engineering, and physical medicine & rehabilitation. The Journal of  NeuroEngineering and Rehabilitation  ( JNER)  is intended to fill this gap and foster cross-fertilizations among these disciplines. By making readily available to clinicians selected studies with potential impact on physical medicine & rehabilitation,  JNER  is anticipated to foster the development of novel and more effective rehabilitation strategies. Conversely, by presenting clinical problems to a readership of neuroscientists and engineers,  JNER  is expected to generate innovative work in neuroscience and biomedical engineering with future applications to physical medicine & rehabilitation.  JNER  will leverage on Open Access as a means to guarantee that its content is readily available to scientists, clinicians, and the general public thus promoting scientific and technological advances that are relevant to rehabilitation.  JNER  is an Open Access initiative. Open Access assures dissemination to the widest possible audience and is seen by many as essential for publicly funded research. BioMed Central offers an outstanding platform to make  JNER  possible and allow neuroscientists, biomedical engineers, and clinicians to see their work published in a timely manner and thus make an immediate impact in the field of rehabilitation.  JNER  will focus on innovative work with higher likelihood of a dramatic impact on rehabilitation. Thus, priority will be given to outstanding and visionary scientific reports, i.e. those proposing exceptionally innovative concepts with great potential in the field.NeuroEngineering and RehabilitationJNER)JNERJNERJNERJNERJNERJNER

A new journal for a quickly evolving research field During the past decade, we have witnessed profound changes in physical medicine & rehabilitation originated by advances in neuroscience and biomedical engineering. For example, imaging and neurological assessment methods have dramatically improved the management of patients with motor impairments; robotics and artificial muscle research have generated revolutionary concepts in orthotics and prosthetics; and advances in cortical recordings and the understanding of central nervous system mechanisms have changed the way clinicians look at movement disorders. These techniques and others have brought about, and will continue to give rise in the future to, dramatic advances in physical medicine & rehabilitation. As advances in neuroscience and biomedical engineering continue to generate new techniques, with tremendous impact in the field of physical medicine & rehabilitation, it becomes apparent that there is an urgent need for establishing an outlet for the intersection of these three research fields.  Journal of NeuroEngineering and Rehabilitation (JNER)  aims to provide such an outlet, hosting the introduction of new methods and the discussion of their clinical implications, and offering an opportunity to publish, in a timely manner, articles relevant to the cross-fertilization of neuroscience, biomedical engineering, and physical medicine & rehabilitation. JNER's  editorial board [ 1 ] demonstrates the commitment of the journal to interdisciplinary research and international representation. Members of the editorial board are leading scientists working in different parts of the world in the research areas of neuroscience, biomedical engineering, and physical medicine & rehabilitation. They share an interest in scientific work that has potential impact on clinical practice in physical medicine & rehabilitation and an enthusiasm for Open Access. The editorial board is pleased to become a part of the growing group of institutions and individuals who work to promote Open Access – BioMed Central currently publishes over 100 Open Access journals covering all areas of biology and medicine, and has over 450 institutional members from about 40 countries.
A new journal for a quickly evolving research field
During the past decade, we have witnessed profound changes in physical medicine & rehabilitation originated by advances in neuroscience and biomedical engineering. For example, imaging and neurological assessment methods have dramatically improved the management of patients with motor impairments; robotics and artificial muscle research have generated revolutionary concepts in orthotics and prosthetics; and advances in cortical recordings and the understanding of central nervous system mechanisms have changed the way clinicians look at movement disorders. These techniques and others have brought about, and will continue to give rise in the future to, dramatic advances in physical medicine & rehabilitation.As advances in neuroscience and biomedical engineering continue to generate new techniques, with tremendous impact in the field of physical medicine & rehabilitation, it becomes apparent that there is an urgent need for establishing an outlet for the intersection of these three research fields.  Journal of NeuroEngineering and Rehabilitation (JNER)  aims to provide such an outlet, hosting the introduction of new methods and the discussion of their clinical implications, and offering an opportunity to publish, in a timely manner, articles relevant to the cross-fertilization of neuroscience, biomedical engineering, and physical medicine & rehabilitation.Journal of NeuroEngineering and Rehabilitation (JNER)JNER's  editorial board [ 1 ] demonstrates the commitment of the journal to interdisciplinary research and international representation. Members of the editorial board are leading scientists working in different parts of the world in the research areas of neuroscience, biomedical engineering, and physical medicine & rehabilitation. They share an interest in scientific work that has potential impact on clinical practice in physical medicine & rehabilitation and an enthusiasm for Open Access. The editorial board is pleased to become a part of the growing group of institutions and individuals who work to promote Open Access – BioMed Central currently publishes over 100 Open Access journals covering all areas of biology and medicine, and has over 450 institutional members from about 40 countries.JNER'sOpen access to advance science and clinical practice JNER's  Open Access policy changes the way in which articles are made available to the scientific community. First, all articles become freely and universally accessible online, and so an author's work can be read by anyone at no cost. Second, the authors hold copyright for their work and grant anyone the right to reproduce and disseminate the article, provided that it is correctly cited and no errors are introduced [ 2 ]. Third, a copy of the full text of each Open Access article is permanently archived in online repositories separate from the journal.  JNER's  articles are archived in PubMed Central [ 3 ], the US National Library of Medicine's full-text repository of life science literature, and also in repositories at the University of Potsdam [ 4 ] in Germany, at INIST [ 5 ] in France and in e-Depot [ 6 ], the National Library of the Netherlands' digital archive of all electronic publications. Open Access has four broad benefits for science and the general public. First, authors are assured that their work is disseminated to the widest possible audience, given that there are no barriers to access their work. This is accentuated by the authors being free to reproduce and distribute their work, for example by placing it on their institution's website. It has been suggested that free online articles are more highly cited because of their easier availability [ 7 ]. Second, the information available to researchers will not be limited by their library's budget, and the widespread availability of articles will enhance literature searching [ 8 ]. Third, the results of publicly funded research will be accessible to all taxpayers and not just those with access to a library with a subscription. As such, Open Access could help to increase public interest in, and support of, research. Note that this public accessibility may become a legal requirement in the US if the proposed Public Access to Science Act is made law [ 9 ]. Fourth, a country's economy will not influence its scientists' ability to access articles because resource-poor countries (and institutions) will be able to read the same material as wealthier ones (although creating access to the internet is another matter [ 10 ]). Open Access will increasingly become an accepted way to disseminate information to the scientific community and the public at large. By becoming part of the movement for Open Access,  JNER  will contribute to make the latest advances in neuroscience and biomedical engineering, which have the potential to impact on the clinical practice of physical medicine & rehabilitation, readily available to scientists, clinicians, and the general public. Because of its inherent interdisciplinary nature,  JNER  will foster further advances in the field thanks to the cross-fertilization among science, technology, and clinical practice. Science and technology are expected to offer new tools to design clinical interventions and, vice versa, clinical problems are anticipated to foster basic research in neuroscience and the development of new technologies. Besides, increased awareness of the way science and technology can improve clinical outcomes will lead to better quality of healthcare in rehabilitation. Changes currently occurring in this field are so dramatic that we expect, in a few years, that modernized rehabilitation inpatient and outpatient units will be completely different from what is the state-of-the-art today. For instance, we envision that continuous monitoring of patient status will be performed via miniature, wireless, wearable sensors which not only allow clinicians to monitor vital signs, but also track motor activities and provide a means to analyze motor patterns associated with recovery. Furthermore, robotic devices will be used to enhance physical therapy, ad hoc protocols will be designed for each patient, and augmented and virtual reality tools will enhance rehabilitation by becoming part of routine exercise protocols.
Open access to advance science and clinical practice
JNER's  Open Access policy changes the way in which articles are made available to the scientific community. First, all articles become freely and universally accessible online, and so an author's work can be read by anyone at no cost. Second, the authors hold copyright for their work and grant anyone the right to reproduce and disseminate the article, provided that it is correctly cited and no errors are introduced [ 2 ]. Third, a copy of the full text of each Open Access article is permanently archived in online repositories separate from the journal.  JNER's  articles are archived in PubMed Central [ 3 ], the US National Library of Medicine's full-text repository of life science literature, and also in repositories at the University of Potsdam [ 4 ] in Germany, at INIST [ 5 ] in France and in e-Depot [ 6 ], the National Library of the Netherlands' digital archive of all electronic publications.JNER'sJNER'sOpen Access has four broad benefits for science and the general public. First, authors are assured that their work is disseminated to the widest possible audience, given that there are no barriers to access their work. This is accentuated by the authors being free to reproduce and distribute their work, for example by placing it on their institution's website. It has been suggested that free online articles are more highly cited because of their easier availability [ 7 ]. Second, the information available to researchers will not be limited by their library's budget, and the widespread availability of articles will enhance literature searching [ 8 ]. Third, the results of publicly funded research will be accessible to all taxpayers and not just those with access to a library with a subscription. As such, Open Access could help to increase public interest in, and support of, research. Note that this public accessibility may become a legal requirement in the US if the proposed Public Access to Science Act is made law [ 9 ]. Fourth, a country's economy will not influence its scientists' ability to access articles because resource-poor countries (and institutions) will be able to read the same material as wealthier ones (although creating access to the internet is another matter [ 10 ]).Open Access will increasingly become an accepted way to disseminate information to the scientific community and the public at large. By becoming part of the movement for Open Access,  JNER  will contribute to make the latest advances in neuroscience and biomedical engineering, which have the potential to impact on the clinical practice of physical medicine & rehabilitation, readily available to scientists, clinicians, and the general public. Because of its inherent interdisciplinary nature,  JNER  will foster further advances in the field thanks to the cross-fertilization among science, technology, and clinical practice. Science and technology are expected to offer new tools to design clinical interventions and, vice versa, clinical problems are anticipated to foster basic research in neuroscience and the development of new technologies. Besides, increased awareness of the way science and technology can improve clinical outcomes will lead to better quality of healthcare in rehabilitation. Changes currently occurring in this field are so dramatic that we expect, in a few years, that modernized rehabilitation inpatient and outpatient units will be completely different from what is the state-of-the-art today. For instance, we envision that continuous monitoring of patient status will be performed via miniature, wireless, wearable sensors which not only allow clinicians to monitor vital signs, but also track motor activities and provide a means to analyze motor patterns associated with recovery. Furthermore, robotic devices will be used to enhance physical therapy, ad hoc protocols will be designed for each patient, and augmented and virtual reality tools will enhance rehabilitation by becoming part of routine exercise protocols.JNERJNEROutstanding and visionary articles make the difference Open Access to outstanding and visionary scientific reports appears to be a tremendous tool to increase the speed at which clinical practice changes as a result of advances in neuroscience and biomedical engineering. By prioritizing outstanding and visionary publications,  JNER  intends to provide a forum for ideas and concepts that could make a difference in physical medicine & rehabilitation by innovating the design of clinical interventions. Publication in  JNER  is free for the first 6 months following the launch of the journal. Manuscripts submitted after this period will be subject to an article-processing charge on acceptance. Waiver requests will be considered on a case-by-case basis, by the Editor-in-Chief. Authors can circumvent the charge by getting their institution to become a 'member' of BioMed Central, whereby the annual membership fee covers the article processing charges for authors publishing in any of the BioMed Central journals. Current members include NHS England, the World Health Organization, the US National Institutes of Health, Harvard, Princeton and Yale universities, and all UK universities [ 11 ]. No charge is made for articles that are rejected after peer review. Many funding agencies have also realized the importance of Open Access publishing and have specified that their grants may be used directly to pay article-processing charges [ 12 ]. The article-processing charges pay for efficient and thorough peer review, for the article to be freely and universally accessible in various formats online, and for the processes required for inclusion in PubMed and archiving in PubMed Central, e-Depot, Potsdam and INIST. Funding available to  JNER's  editorial board will be solely used to further promote the journal and to continuously increase the scientific quality of  JNER's  articles. The first articles published in the journal demonstrate the commitment of  JNER  to high quality, prioritizing visionary work, and focusing on research that has the potential of a great impact on physical medicine & rehabilitation. Forthcoming articles will further prove such commitment. Topics of interest to come in the next few months are virtual and augmented reality in rehabilitation, wearable technology in rehabilitation, methods for the analysis of movement, and robotics applied to rehabilitation. These are all topics of great relevance for the research at the intersection of neuroscience, biomedical engineering, and physical medicine & rehabilitation. Special thanks to the authors of the first articles published in  JNER  as well as to the authors who submit their manuscripts in the future and support our journal and the Open Access initiative. Members of the editorial board and reviewers have done some excellent work; special thanks to them and the Managing Editor, Sara Midwood, for their contributions to  JNER .
Outstanding and visionary articles make the difference
Open Access to outstanding and visionary scientific reports appears to be a tremendous tool to increase the speed at which clinical practice changes as a result of advances in neuroscience and biomedical engineering. By prioritizing outstanding and visionary publications,  JNER  intends to provide a forum for ideas and concepts that could make a difference in physical medicine & rehabilitation by innovating the design of clinical interventions.JNERPublication in  JNER  is free for the first 6 months following the launch of the journal. Manuscripts submitted after this period will be subject to an article-processing charge on acceptance. Waiver requests will be considered on a case-by-case basis, by the Editor-in-Chief. Authors can circumvent the charge by getting their institution to become a 'member' of BioMed Central, whereby the annual membership fee covers the article processing charges for authors publishing in any of the BioMed Central journals. Current members include NHS England, the World Health Organization, the US National Institutes of Health, Harvard, Princeton and Yale universities, and all UK universities [ 11 ]. No charge is made for articles that are rejected after peer review. Many funding agencies have also realized the importance of Open Access publishing and have specified that their grants may be used directly to pay article-processing charges [ 12 ].JNERThe article-processing charges pay for efficient and thorough peer review, for the article to be freely and universally accessible in various formats online, and for the processes required for inclusion in PubMed and archiving in PubMed Central, e-Depot, Potsdam and INIST. Funding available to  JNER's  editorial board will be solely used to further promote the journal and to continuously increase the scientific quality of  JNER's  articles.JNER'sJNER'sThe first articles published in the journal demonstrate the commitment of  JNER  to high quality, prioritizing visionary work, and focusing on research that has the potential of a great impact on physical medicine & rehabilitation. Forthcoming articles will further prove such commitment. Topics of interest to come in the next few months are virtual and augmented reality in rehabilitation, wearable technology in rehabilitation, methods for the analysis of movement, and robotics applied to rehabilitation. These are all topics of great relevance for the research at the intersection of neuroscience, biomedical engineering, and physical medicine & rehabilitation.JNERSpecial thanks to the authors of the first articles published in  JNER  as well as to the authors who submit their manuscripts in the future and support our journal and the Open Access initiative. Members of the editorial board and reviewers have done some excellent work; special thanks to them and the Managing Editor, Sara Midwood, for their contributions to  JNER .JNERJNER