Bile Acid Concentrations in Serum and Duodenal Aspirates of Healthy Preterm Infants: Effects of Gestational and Postnatal Age

Abstract

In 41 healthy human-milk-fed preterm infants the preprandial total bile acid (B A) concentrations in serum and duodenal juice were simultaneous measured during the first 60 days of life. The infants were subdivided into four groups according to their gestational age: 6 infants with a gestational age of 27 and 28 weeks, 7 infants with a gestational age of 29 and 30 weeks, 21 infants with a gestational age of 31 and 32 weeks and 7 infants with a gestational age of 33 and 34 weeks. The BA levels were enzymatically determined using 3-α-hydroxysteroid dehydrogenase. In the duodenal juice, cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid and lithocholic acid were separately quantified by thin-layer chromatography. During the first month of life, the serum BA concentrations increased significantly with postnatal age (p < 0.01) but remained nearly constant during the second month of life. In the duodenal aspirates, the BA concentrations increased continuously up to the end of the observation period (p < 0.001). In the duodenal aspirates, the CA/CDCA ratio was high immediately after birth and decreased significantly with increasing postnatal age (p < 0.001). During the first weeks of life, the BA levels were preferentially conjugated with taurine, but in spite of the taurine-rich diet during the whole observation period the taurine/glycine ratio decreased with postnatal age (p < 0.001). In all samples of duodenal juice, the sum of primary BA was > 98% of total 3-α-hydroxy-BA. These data indicate that the establishment of an intestinal microbial flora necessary for intestinal BA transformation and the development of the enterohepatic BA circulation lasts some months of postnatal life. The serum BA concentration reflects hepatic synthesis, intestinal absorption, renal excretion and hepatocellular transport into bile in a very complex way which may limit the diagnostic value of serum BA during this time. Additionally, a duodenal BA concentration below 4 mmol/l, as found in this study during the first 2 weeks of life, may be of clinical importance due to its possible effects on fat absorption.

Fetal Bile Acid Metabolism: Analysis of Urinary 3β-Monohydroxy-Δ⁵ Bile Acid in Preterm Infants

“…Another possibility for evaluating bile acid metabolism would be the measurement of bile acids in serum and/or duodenal fluid in addition to urine, but sampling would be extremely difficult. Bile acids have been reported to increase in serum with postnatal age until the end of the first month [15]. This pattern is similar to that for concentrations of urinary bile acids in our study.…”

“…0.0001). Similar information has been reported by Boehn et al [15]. However, this finding in preterm infants differed from that in full-term infants [1,2,4].…”

“…Therefore, we suspect that concentrations of urinary bile acids expressed as micromoles per millimole Cr reflect those of bile acids in serum. Concentrations of bile acids in serum also reflect enterohepatic bile acid circulation during early infancy [15].…”

Ontogenetic Development of Rat Intestinal Bile Acid Transport Requires Thyroxine But Not Corticosterone

“…These concentrations lead to uptakes that are near the V max for each substrate, and the V max determinations are not affected by errors caused by unstirred layers (20). For taurocholate, 6 mM is also close to the estimated taurocholate concentrations in the intestinal lumen (21). The range of human luminal bile acid concentrations is 0.1 mM (cholic acid) to 12 mM (glycocholic acid) (22).…”

The Newborn Drug Development Initiative

“…Factors affecting the oral bioavailability of drugs include decreased acid secretion, 5 prolonged intestinal transit time, 6 and a decreased bile acid pool. 7 Skin permeability is increased in very low birth weight infants, favoring the dermal absorption of topically applied drugs. 8 The relatively small muscle mass and decreased muscle blood flow in low birth weight infants may slow the absorption rate of drugs administered by the intramuscular route.…”