Bilirubin Levels in Infancy and Their Associations with Body Weight, Levels of Iron-Related Parameters and Steroid Hormone Levels

Abstract

It is assumed that bilirubin is hormonally regulated and influences weight development by preventing weight gain. However, studies in healthy infants are limited. The present study established reference values for bilirubin and investigated whether bilirubin levels are significantly associated with body weight, levels of ferritin and transferrin as well as steroid hormone levels in a study population of three- and six-month-old healthy infants. Data from a total of 411 study visits from the LIFE Child study (Leipzig, Germany) were analyzed. Associations were examined using linear regression analyses. Besides laboratory parameters, anthropometric data were gathered. We found statistically significant associations between body weight and bilirubin levels. In girls, we observed additional associations between bilirubin levels and both ferritin and transferrin concentrations at three months of age. At six months, steroid hormone levels were significantly associated with concentrations of total and indirect bilirubin, with effects differing by sex. Our study thus confirms associations already reported from animal studies and studies in adult populations. Furthermore, we showed that these associations already exist in the first year of life, are influenced by sex and age and, further, depend on the bilirubin type. Our results provide reference values for bilirubin and assist, therefore, in interpreting bilirubin levels in infancy.

Keywords: bilirubin; body weight; ferritin; infancy; steroid hormones; transferrin.

Figure 1

Distribution and reference ranges of (a) total (n = 376), (b) direct (n = 290) and (c) indirect (n = 161) bilirubin values in our healthy study population of infants at the age of three and six months. Dots represent the distribution of measured bilirubin values. The 2.5th percentile (P2.5), 97.5th percentile (P97.5) and the 95% confidence interval are marked in orange The reference ranges for bilirubin at the age of three months were wider than those at six months of age.

Figure 1

Distribution and reference ranges of (a) total (n = 376), (b) direct (n = 290) and (c) indirect (n = 161) bilirubin values in our healthy study population of infants at the age of three and six months. Dots represent the distribution of measured bilirubin values. The 2.5th percentile (P2.5), 97.5th percentile (P97.5) and the 95% confidence interval are marked in orange The reference ranges for bilirubin at the age of three months were wider than those at six months of age.

Figure 2

Associations between total bilirubin levels at three and six months of age and body weight during healthy children clinics (German: Kinder-Vorsorgeuntersuchungen) stratified by age and adjusted for sex. The association between bilirubin levels measured at three months of age and body weight is depicted in orange. The association between bilirubin levels measured at six months of age and body weights is depicted in light blue. Effect sizes were determined by linear regression analyses. The error bars show the 95% confidence intervals. Associations with statistical significance are marked. In general, total bilirubin levels were negatively associated with body weight. Statistical significance was reached for the associations between total bilirubin levels at three months of age and weight at healthy children clinics after birth (U1), third to tenth day after birth (U2) and fourth to fifth week after birth (U3).

Figure 3

The associations between the levels of ferritin/transferrin and concentrations of (a) total bilirubin, (b) direct bilirubin and (c) indirect bilirubin were assessed stratified by sex in three-month-old infants using linear regression analysis. Dots represent the individual measurements. The semi-transparent background shows the confidence region of the associations. Levels of iron-related parameters were related to bilirubin levels in girls but not in boys. Whereas ferritin levels were positively associated with the levels of the three types of bilirubin, transferrin concentrations were inversely related to bilirubin concentrations.

Figure 3

The associations between the levels of ferritin/transferrin and concentrations of (a) total bilirubin, (b) direct bilirubin and (c) indirect bilirubin were assessed stratified by sex in three-month-old infants using linear regression analysis. Dots represent the individual measurements. The semi-transparent background shows the confidence region of the associations. Levels of iron-related parameters were related to bilirubin levels in girls but not in boys. Whereas ferritin levels were positively associated with the levels of the three types of bilirubin, transferrin concentrations were inversely related to bilirubin concentrations.