Fecal elastase-1 in healthy children up to 2 years of age: a cross-sectional study

Elastase-1 (E-1) is a marker of exocrine pancreatic insufficiency that is widely used owing to its high specificity and sensitivity [1, 2, 3, 4, 5]. Low fecal E-1 concentrations occur in diseases involving pancreatic dysfunction, such as: cystic fibrosis, diabetes, chronic pancreatitis, pancreatic cancer, coeliac disease and human immunodeficiency virus infection [6, 7, 8, 9, 10].

The abundance of E-1 in stools depends on a person’s diet and age. Our previous research revealed that abstaining from meat results in a significant decrease in E-1 [11, 12] and that E-1 levels in the elderly are lower compared with young people, reflecting the natural aging of the pancreas [13]. Many different changes may be expected to be found in infants and young children since their gastrointestinal tract is immature and their diet differs from that of adults. However, the available data regarding fecal E-1 concentrations in healthy children, and especially in infants, is scarce. In fact, most of the studies conducted to-date described the evolution observed in the secretion of pancreatic enzymes over the first days after birth in preterm infants and measuring E-1 levels in their meconium [14, 15, 16]. Low E-1 concentrations in the meconium and their increase in feces in the first weeks of life was noted in these studies. However, research which would involve representative groups of healthy infants and toddlers is still lacking.

The aim of this cross-sectional study was to evaluate fecal E-1 concentrations in infants and children from 1 up to 24 months of age.

The anthropometric parameters describing the subjects are presented in Table 1. No statistically significant differences between Z-scores for body weight and sex were found between the groups (Table I).

Fecal E-1 concentrations ranged from 200 to 1695 μg/g of feces. No child had fecal E-1 levels below the cut-off level (200 μg/g) suggestive of abnormal exocrine pancreatic function.

Fecal E-1 concentrations did not significantly differ between age groups (Table II). However, fecal E-1 levels in the first 3 months were lower than in the second year of life (median [1^st-3^rd quartile], 790 μg/g [527-920] vs 900 μg/g [728-1070]; p=0.0230). A statistically significant correlation between E-1 concentration and age was found (p=0.0007, r=0.2639; however, it does not affect the cutoff level of the reference values). The trend observed was rather exponential (Figure 1). Fecal E-1 values reached a plateau around the age of 6-10 months.

Fig. 1

The topic of our study was the evaluation of fecal E-1 concentrations in healthy children aged 1-24 months. This has been the first time when in such a large cohort of healthy infants and young children (n=160) exocrine pancreatic function was studied using reliable indirect pancreatic function tests. It should be emphasized that this is the first study to create reference values of E-1 in healthy infants and toddlers.

E-1 concentrations in all children were within the normal range for adults. Similarly, Nissler et al. reported that 96.8% of the infants they studied had higher fecal E-1 levels after the second week of life than the adult lower limit of normal values, independent of the gestational age at which they were born [16]. However, their study comprised predominantly patients younger than 3 months with only a few older infants. It should be noted that the youngest child in the present study was older than 4 weeks and no meconium assessments were made. We did not include neonates, because extensive data are already available for this age group [14, 15, 16,19, 20, 21]. Kori et al. noted that in all the samples analyzed (n=63) regardless of gestational age, the E-1 level was below normal range (200 μg/g of feces; mean (SD) 45.9 μg/g of feces (51.1)) and found that E-1 normalization followed day 3 in term newborns [14]. Also in preterm babies studies described a low E-1 concentration in their first few days of life (median (range): 89 μg/g of feces (3-539) at day 2) which gradually increased on subsequent days (median (range): 164 μg/g of feces (3–600 at day 5) [15].

In our study fecal E-1 levels were lower within the first months of life. Later they reached a plateau corresponding to normal adult levels. Also Terbrack et al. described a slight tendency of E-1 levels to increase with age and similarly high enzyme concentrations in a population of older infants and children (the mean was 763 μg/g) [19]. However, a detailed analysis was performed only for the first 4 months of life (4 groups aged 1, 2, 3 and 4 months). Older subjects were divided into 2 groups with a large age span (the first group − from 5 months to 1 year, the second − from 1 year to 14 years).

The increase of values observed within the first months of life in the present study may be due to the development of the pancreas. Although the pancreas begins to produce enzymes already in the 20^th week of gestation, newborns secrete fewer pancreatic enzymes than older children (for example, amylase levels are undetectable, while lipase is produced on a level of less than 10% of childhood levels) [22, 23]. It should be noted that the ontogeny of E-1 in infants is still unknown.

The documented differences in fecal E-1 concentration between age subgroups might be related to weaning and expanding infants’ diet (especially by the 6^th month of life). In the data available, the normal levels of fecal E-1 were found sooner in infants who started enteral feeding earlier [14, 15]. It should, however, be noted that infants are fed a very specific (high fat) diet based exclusively on milk fat. On the other hand extending their diet may stimulate enzyme production and secretion, which is supported by studies on adults that have shown that an abstinence from meat may lead to a decrease in fecal E-1 concentration [11].

It should be stressed that the abundant data concerning fecal E-1 concentrations in children with cystic fibrosis [24, 25, 26, 27] or preterm infants [14, 15, 21] cannot be extrapolated from healthy infants. All the studies conducted on healthy children so far involved heterogenous age groups (from birth to almost adulthood) with low numbers of infants and toddlers [28, 29]; this renders the results virtually uninterpretable beyond the neonatal and early post-neonatal period.

Although the present study comprises a large and representative group of infants and young children aged up to 24 months, it also has some limitations which includes the cross-sectional character of the study with the lack of longitudinal follow-up of fecal E-1 concentrations, the absence of information on the weaning status, and the lack of correlation of fecal E-1 levels to energy and nutrient intake.

Our study has shown that the fecal E-1 test can be reliably applied in infants and toddlers to confirm normal exocrine pancreatic function. However, within the first months of life fecal E-1 concentrations may be lower than later in life.