Delay in caffeine elimination in breast-fed infants.

Because of a persistently elevated caffeine half-life observed in a breast-fed infant during caffeine maintenance therapy, we conducted this prospective longitudinal study in two groups of infants (five exclusively breast-fed and 12 formula-fed). After 46 weeks' postconceptional age, all five breast-fed infants had a marked delay in caffeine elimination, compared with one infant in the formula-fed group. Four breast-fed infants had measurements of significantly longer caffeine half-lives compared with 12 formula-fed infants (76 +/- 13 hours v 21 +/- 28 hours and 54 +/- 9 hours v 16 +/- 13 hours at 47 to 50 weeks and 51 to 54 weeks postconceptional age, respectively), as well as significantly higher trough blood levels (three- to five-fold) after 46 weeks' postconceptional age. The fifth breast-fed infant accumulated caffeine secondary to a steep increase in caffeine half-life from 102 hours at 44 weeks to 372 hours at 51 weeks. The elevated blood caffeine levels in breast-fed infants was not related to higher daily dosage of caffeine citrate (4.4 mg/kg compared with 8.3 mg/kg in the formula-fed group at 56 weeks' postconceptional age). Daily consumption of caffeine was low or nonexistent in four nursing mothers, and transfer of caffeine to the infant was considered to be trivial. The findings from this study suggest, as does breast milk jaundice due to inhibition of glycuronyl transferase, that some components of human milk (free fatty acid, lipase activity, or other factors) inhibit or repress the postnatal normal maturation process of caffeine metabolism by hepatic cytochrome P-450.

Maturational changes of caffeine concentrations and disposition in infancy during maintenance therapy for apnea of prematurity: influence of gestational age, hepatic disease, and breast-feeding.

Twenty-three premature infants receiving caffeine maintenance therapy were followed prospectively for several months. Three to nine determinations of caffeine half-life (peak and trough caffeine levels) were made in each baby. This first longitudinal study confirmed that the half-life of caffeine is prolonged during the neonatal period (97.6 + 32 hours and for as many as 38 weeks' gestation in several very premature babies). Contrary to previous assumptions, gestational age and postconceptional age seem to be closely related to maturation of hepatic caffeine elimination after the neonatal period, although a high variability of caffeine half-life was observed between infants. Adult values (6 hours) were obtained about 60 weeks postconceptional. Caffeine half-life was greatly increased in two infants who had cholestatic hepatitis secondary to prolonged parenteral alimentation and one infant who was breast-fed exclusively. In this last case, the role of maternal hormones in repressing the normal enzymatic maturation process is strongly suspected. Adequate blood levels of caffeine were usually obtained with a caffeine half-life greater than 30 hours up to 46 weeks postconceptional with a dose of 5 mg/kg of caffeine citrate. Caffeine predose monitoring is adequate up to 46 weeks postconceptional, and caffeine half-life determination is mandatory whenever the trough level is too high or too low, icterus is present, and from 46 to 50 weeks postconception.

[Spinal hyperostosis and disorders of retinol metabolism]. / Hyperostose vertébrale et troubles du métabolisme du rétinol.

Vitamin A or its acid derivatives can be responsible for bony lesions similar to those in ankylosing hyperostosis in animals and in man. We performed a controlled, prospective study on vitamin A metabolism in 23 patients with ankylosing hyperostosis and in 17 normal controls. Beta-carotene serum levels were determined by spectrophotometry, and retinol serum levels by inverse phase high performance liquid chromatography, and retinol binding protein (RBP) by radial immunodiffusion. After eliminating the causes which disturb vitamin A metabolism or RBP, we found a significant increase in retinol (p less than 0.02), in the molar relationship, retinol/RBP (p less than 0.05), without zinc deficiency. The association of diabetes with ankylosing hyperostosis normalizes in a statistically significant manner serum retinol levels (p less than 0.05), but apparently does not modify the increased molar relationship, retinol/RBP. These findings suggest a toxic effect of retinol due to the increased amount of free retinol or by nonspecific transport by proteins other than RBP.

Patterns of change in selected serum chemical parameters of middle and later years.

Six serum constituents known to vary with renal function were analyzed in a probability sample of 500 persons 55 years and over, and their sex trends compared to other ages. Creatinine, BUN and alkaline phosphatase are elevated in this group whereas calcium is low and phosphorus strikingly so, especially in males. A possible explanation lies in age-related renal parenchymal changes which influence both glomerular filtration and tubular functions in ways that differ from true renal disease. These results have directed implications for geriatric diagnosis and therapy.

Use of values for calcium and protein in serum, and of a derived index obtained from a probability population sample.

We measured serum protein and calcium concentrations in 2340 individuals between 10 and 96 years of age from 900 families chosen by probability methods to give a representative population. These values were used to calculate an index, based on a regression analysis of serum protein on calcium, which was then treated as a new variable. Age-sex specific reference values and frequency distributions are presented for this index as well as for protein and calcium calculated by both parametric and nonparametric methods.