approximately 10% of children seen in primary care develop signs of failure to thrive ( ftt ) .
children who do not respond to treatment for inadequate caloric intake or have a suspected  organic  cause get further laboratory diagnosis to identify the 1% of cases with ftt that result from diagnosable disease . in addition to inadequate caloric intake and caloric absorption , excessive caloric consumption due to hyperthyroidism , malignancy , and chronic disease such as severe heart failure ( hf ) must be considered .  
elevated n - terminal pro brain natriuretic peptide ( n - bnp ) levels were found in children with severe hf due to congenital heart disease or dilated cardiomyopathy [ 1 , 2 ] . from 2005 to 2008
we included n - bnp measurements in our laboratory program for infants with ftt in an attempt to use a laboratory test to identify infants who suffer from severe hf .
surprisingly we found significantly elevated n - bnp in infants with ftt without any evidence for cardiac disease .  
the purpose of this study was to compare n - bnp levels in infants with ftt with infants with   severe hf and healthy controls from recently published n - bnp values .
consecutive infants who were admitted to our hospital with ftt and bodyweight below the tenth percentile from 2005 to 2008 were included . those infants with an organic cause of ftt like short bowel syndrome or endocrinologic disease
the remaining infants of the caloric deprivation ( cd ) group suffer from failure to thrive due to inadequate caloric intake and inappropriate type or volume of feeding .
the infants with severe hf due to congenital heart disease were taken together in the  heart failure  group .
normal n - bnp values shown in figure 1 were taken from the literature . for statistical analysis shown in table 2 , we received the original data for healthy infants from   norozi et al .   and koch et al . .
peripheral venous blood samples were obtained from all participants , after a rest for at least 15 minutes .
the subjects were in the supine position during blood sampling , which was typically done between 8:30 a.m. and 11:00 a.m. the blood samples were immediately placed on ice and subsequently centrifuged at 5000  rpm for 10 minutes . in all children
n - bnp was determined using immunoassay ( elecsys 2010 , roche , germany ) .
we excluded all infants with  organic  cause for ftt like short bowel syndrome or endocrinologic disease .
each patient had normal c - reactive protein values and   therefore we could exclude significant inflammation .
n - bnp serum concentrations are markedly elevated in the first days of life in healthy neonates , probably due to circulatory changes in the perinatal period .
the mann - whitney test was used for comparison of n - bnp values of our patients and the original data from healthy infants published by norozi et al .   and koch et al . .
the data analyses were performed using excel 2000 ( microsoft , usa ) and prism ( graphpad software inc .
demographic and height and weight characteristics for the three study groups are summarized in table 1 .
26 patients were included in our study , the cd group contained 15 patients , and the hf group contained 11 patients .
there is no significant statistical difference in age , bodyweight , body length , gestational age , and head circumference in the cd group and the hf group .
the cd group had a significantly lower postnatal weight gain 73 ( 0147 )  g / week at home mostly caused by inadequate breast feeding at home , compared with the weight gain during hospital stay 225 ( 100500 )  g / week .
further laboratory investigations show no significant difference for haemoglobin , white blood cells , alt , and creatinine values in infants with hf compared to the infants with ftt .
the hf group included 7 infants prior to cardiac surgery ( ventricular septal defects or atrioventricular septal defects ) .
four infants suffered from severe hf more than 2 weeks after cardiac surgery ( transposition of the great arteries , single ventricle ) .
seven infants with severe hf received a medical therapy with digoxin , diuretics , angiotensin converting enzyme inhibitors , and/or beta - blocker .
our results show that infants with ftt had significantly elevated n - bnp values compared with the healthy infants 115 ( 151121 )  pg / ml versus 530 ( 1193150 )  pg / ml , p < .001 .
n - bnp values in the cd group are not significantly different from values of infants with severe hf 673  pg / ml , ( 408  35000 )  pg / ml .   as shown in figure 1 n - bnp of our healthy infants group
brain natriuretic peptide is secreted mainly by cardiac myocytes of the ventricles and to a lesser degree of the atria .
however , several recent studies demonstrate an inverse relationship between body mass index and n - bnp levels were completed in adults with and without severe hf . in this study
we present significant n - bnp elevations in a group of 15 infants with cd .
these infants only suffer from an inadequate caloric intake without any evidence for severe hf , congenital heart disease , and liver or kidney disease .
there was no evidence of diastolic dysfunction on the echocardiograms , indicated by normal mitral valve inflow profiles . in our study
the age of the remaining infants was in good accordance with the reference group of the literature .
the median n - bnp level of our infants with ftt 530 ( 1193150 )  pg / ml ) is comparable to children with ross class iii hf ( 744  pg / ml ) .
our heart failure group included only infants with severe hf with a very high n - bnp level of 40835000  pg / ml .
these data are in good accordance with data from a pilot study regarding n - bnp in patients with hf due to ventricular septal defects showing that the perioperative change in n - bnp was most closely correlated with improved weight gain .
also it is well known from adults with severe hf that cachectic patients have the highest n - bnp levels .  
although the reason for the relationship between body mass index and n - bnp is unknown , the increased concentration of the natriuretic peptide receptor - c clearance receptor on adipocyte cells has led some to postulate that increased clearance is the reason for lower n - bnp levels in obese patients .
however , evidence against this hypothesis comes from das et al . , who found that n - bnp was correlated with greater lean mass but not greater fat mass .
this may represent preservation of the physiological response to change in body fat but might also suggest that adiponectin plays a role in the pathogenesis of cachexia .
the correlation between bnp and adiponectin also raises the possibility that the former might increase the secretion of the latter . in an experimental setting tsukamoto
could show that administration of bnp over 14 days in rats increased the plasma adiponectin concentration and concluded that bnp enhances adiponectin production in adipocytes , and bnp is a potential regulator of adiponectin production .  
ohara et al . found that the plasma adiponectin level increased along with an increase of plasma bnp in healthy subjects independently of other confounding factors and they concluded that adiponectin reflects cardiac function .
for example , the authors who published the reference values of n - bnp serum concentrations in healthy neonates and children did not give any information about the bodyweight of their study group .  
this may be the reason for their high range of reference values ( 51121  pg / ml ) in so - called healthy infants between 2 and 12 months .  
we urgently need reference values from infants with a well - documented normal nutritional state .
further studies may delineate whether measuring n - bnp levels are useful for the initial evaluation or ongoing management of patients with ftt due to either inadequate caloric intake or severe hf .  
the pathophysiological consequence of elevated natriuretic peptides in children with ftt with regard to volume regulation , blood pressure , and cardiovascular prognosis remains speculative .
our observation reveals new horizons for the explanation of well - known cardiovascular risk factors like the enhanced cardiovascular mortality in patients with low birth weight or ftt during infancy ( barker hypothesis ) .
the link between low birth weight and ftt in infancy , catch - up growth in early childhood , and the higher risk of death from coronary heart disease in adults is important but yet not well understood .
longitudinal n - bnp measurements in these patient groups may help for a better pathophysiological understanding of barkers hypothesis and risk stratification in infants with low birth weight and fft .  
a statistical problem is based upon the high range of n - bnp values in healthy infants especially in the first four weeks of life .
due to the nature of our retrospective study we were not able to measure adiponectin in our patients , which could be very helpful for interpretation of enhanced n - bnp , especially if there were a correlation between the level of adiponectin and n - bnp .
additional limitations of the study include the fact that there are a relatively small number of patients , and that data were obtained at a single time point without additional follow - up values .
 
 background . brain natriuretic peptide and its inactive fragment n - terminal pro - bnp ( n - bnp ) are reliable markers of ventricular dysfunction in adults and children . 
 we analyzed the impact of nutritional state on n - bnp levels in infants with failure to thrive ( ftt ) and in infants with severe heart failure ( hf ) . 
 the purpose of this study was to compare n - bnp levels in infants with ftt with infants with severe hf and healthy controls . 
 
 methods . in a retrospective cohort study , we compared n - bnp levels from all consecutive infants with ftt and bodyweight below the tenth percentile ( caloric deprivation ( cd ) group ) to infants with severe hf . 
 reference values from infants between 2 and 12 month were taken from the literature and healthy infants . 
 results . 
 our results show that infants with ftt ( n = 15 ) had significantly ( p < .001 ) elevated n - bnp values compared with the healthy infants ( n = 23 ) , 530 ( 1193150 )  pg / ml versus 115 ( 151121 )  pg / ml . n - bnp values in this cd group are comparable to the median value of infants with severe hf ( n = 12 ) 673 ( 40811310 )  pg / ml . there is no statistical significant difference in age . conclusion . 
 nutritional state has an important impact on n - bnp levels in infants with ftt . 
 we could show comparable levels of   n - bnp in infants with ftt and infants with severe hf . 
1. Introduction
2. Methods
3. Results
4. Discussion