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


METHODS
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 4β-hydroxycholesterol and cholesterol.


RESULTS
The 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.


CONCLUSIONS
Pregnancy 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.
Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, 141 86, Stockholm, Sweden.
Hanna
H
Nylén
Sofia
S
Sergel
Lisa
L
Forsberg
Synnöve
S
Lindemalm
Leif
L
Bertilsson
Katarina
K
Wide
Ulf
U
Diczfalusy
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D007223:Infant; D007231:Infant, Newborn / Q000097:blood*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy / Q000097:blood*; D013997:Time Factors
D015415:Biomarkers; D006888:Hydroxycholesterols; C099828:cholest-5-ene-3,4-diol; D002784:Cholesterol; D051544:Cytochrome P-450 CYP3A
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