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

purposeThe purpose of this study was to determine the 4β-hydroxycholesterol to cholesterol ratio in mothers and neonates at the time of birth and 4 months post-partum.

method21 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 4β-hydroxycholesterol and cholesterol.

resultsThe median plasma concentration of 4β-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 4β-hydroxycholesterol. The major cause is an increased CYP3A activity during pregnancy. The median 4β-hydroxycholesterol/cholesterol ratio·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 4β-hydroxycholesterol/cholesterol ratio·10(4) (0.19) comparable to adults already at birth, but lower 4β-hydroxycholesterol (12 ng/mL) and cholesterol (1.8 mmol/L) concentrations.

conclusionPregnancy leads to increased CYP3A enzyme activity as determined by the 4β-hydroxycholesterol/cholesterol ratio. Neonates have low 4β-hydroxycholesterol and cholesterol concentrations but similar total CYP3A activity as adults already at birth.