Cytochrome P450 3A activity in mothers and their neonates as determined by plasma 4β-hydroxycholesterol

The purpose of this study was to determine the 4 beta-hydroxycholesterol to cholesterol ratio in mothers and neonates at the time of birth and 4 months post-partum. 21 mothers and 22 neonates were recruited at the delivery ward at Karolinska University Hospital, Huddinge, Sweden. Blood samples taken from mothers and neonates at birth and 4 months post-partum were analysed for 4 beta-hydroxycholesterol and cholesterol. The median plasma concentration of 4 beta-hydroxycholesterol was higher in mothers at delivery (50 ng/mL) compared to healthy non-pregnant women (29 ng/mL). The pregnant women had a higher median cholesterol concentration (6.2 mmol/L) compared to healthy non-pregnant women (4.6 mmol/L) but this could only partly explain the increased 4 beta-hydroxycholesterol. The major cause is an increased CYP3A activity during pregnancy. The median 4 beta-hydroxycholesterol/cholesterol ratio center dot 10(4) was elevated in mothers at time of birth compared to non-pregnant women (0.19 and 0.15, respectively) but decreased to 0.15 4 months post-partum. Neonates had a median 4 beta-hydroxycholesterol/cholesterol ratio center dot 10(4) (0.19) comparable to adults already at birth, but lower 4 beta-hydroxycholesterol (12 ng/mL) and cholesterol (1.8 mmol/L) concentrations. Pregnancy leads to increased CYP3A enzyme activity as determined by the 4 beta-hydroxycholesterol/cholesterol ratio. Neonates have low 4 beta-hydroxycholesterol and cholesterol concentrations but similar total CYP3A activity as adults already at birth.