Reduced fetal exposure to aspirin using a novel controlled-release preparation in normotensive and hypertensive pregnancies.
OBJECTIVE
To examine the fetal effects of a novel controlled-release, low dose aspirin preparation in normal and hypertensive pregnancies.


METHODS
Random double-blind study. Participants assigned to receive conventional formulation aspirin (75 mg), controlled-release low dose aspirin (75 mg), or a matching placebo.


METHODS
National Maternity Hospital, Dublin.


METHODS
Eighteen women with an uncomplicated pregnancy and 18 women with preeclampsia.


METHODS
Urine was analysed for metabolites of thromboxane and prostacyclin by gas chromatography, mass spectrometry. Serum thromboxane B2 was determined in maternal and cord blood.


RESULTS
Both aspirin preparations reduced maternal serum thromboxane B2 by 95% and induced similar reductions in the urinary 11-dehydro-thromboxane B2, a major metabolite of thromboxane A2 in vivo. In contrast, neither preparation altered urinary 2,3-dinor-6-keto PGF1alpha, the major metabolite of prostacyclin. Despite their similar effects in the mothers, the two aspirin preparations differed in their effects on the fetus. While both suppressed cord fetal thromboxane B2, this was significantly (P < 0.005) less for the controlled-release preparation (210+/-42 ng/ml for placebo vs 109+/-22 ng/ml for controlled-release aspirin and 44+/-9 ng/ml for regular oral aspirin).


CONCLUSIONS
At equivalent maternal suppression of serum thromboxane B2, a controlled aspirin release preparation results in lower fetal exposure than regular oral aspirin.
Centre for Cardiovascular Science, Royal College of Surgeons in Ireland and the National Maternity Hospital, Dublin.
C L
CL
Regan
B F
BF
McAdam
P
P
McParland
P C
PC
Boylan
G A
GA
FitzGerald
D J
DJ
Fitzgerald
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000378:metabolism; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D015777:Eicosanoids / Q000652:urine; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D011225:Pre-Eclampsia / Q000188:drug therapy*; D011247:Pregnancy; D013929:Thromboxane B2 / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D003692:Delayed-Action Preparations; D015777:Eicosanoids; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D001241:Aspirin