Cholesterol dynamics in the foetal and neonatal brain as reflected by circulatory levels of 24S-hydroxycholesterol

Oxysterols, particularly those hydroxylated in the steroid side-chain, are formed from cholesterol by specific cytochrome P450 enzymes and may facilit ate elimination of cholesterol from extrahepatic sources. In humans, the gr eatest portion of circulating 24S-hydroxycholesterol (24S-OH-Chol) is deriv ed from the brain and the absolute concentration depends on age. In the pre sent study, concentrations of 24S-OH-Chol and for comparison 27-OH-Chol wer e determined by a highly sensitive isotope dilution method using gas chroma tography-mass spectrometry in serum samples from normal preterm and term ne onates and those with Rhesus haemolytic disease, taken serially for diagnos tic purposes. Serum concentrations of cholesterol, 24S-OH-Chol and 27-OH-Ch ol were similar in venous versus arterial cord blood of 6 term neonates. Se rum concentrations of 24S-OH-Chol acid 27-OH-Chol in 12 small for gestation al age (SGA) preterm neonates were significantly lower than those in 12 app ropriate for gestational age (AGA) preterm neonates (P < 0.001), and also l ower than those in 12 SGA (p < 0.001) and 12 AGA term neonates (p < 0.05). Serum cholesterol was significantly higher in preterm than in term neonates (p < 0.001). 24S-OH-Chol serially determined in 8 infants with Rhesus haem olytic disease increased 5-6-fold during the first 3 mo after birth (from 4 2 +/- 20 ng ml(-1) to 227 +/- 71 ng ml(-1)). 27-OH-Chol increased simultane ously from 30 +/- 14 ng ml(-1) to 100 +/- 39 ng ml(-1). Conclusion: Serum concentrations of 24S-OH-Chol increased 5-6-fold after bi rth. This could be an indication of normal cholesterol metabolism in the de veloping neonatal brain.