The role of thromboxane A2 in the pathogenesis of intrauterine growth restriction associated with maternal smoking in pregnancy

BackgroundTo examine the effect of maternal smoking in pregnancy on the production of two eicosanoids, thromboxane A2 and prostacyclin I2, and their role in the pathogenesis of intrauterine growth restriction.MethodsProspective case control study enrolled smoking and non-smoking women at ≤14 weeks gestation. Maternal urine samples were obtained at ≤14, 28 and 36 weeks. High performance liquid chromatography tandem mass spectrometry (LC–MS–MS) was used to quantify 11-dehydrothromboxane B2 (TX-M) and 2,3 dinor-6-ketoprostaglandin F1α (PG-M), stable urinary metabolites of thromboxane A2 and prostacyclin I2. Confirmation of the smoking status was performed by quantitation of urinary nicotine metabolites. Data was analysed using SPSS and Stata®.ResultsThirty five were enrolled in the smoking group and 32 in the non-smoking group. Smoking resulted higher levels of TX-M at ≤14, 28 and 36 weeks gestation. There was no difference in PG-M at any gestational time point between the two groups. The median customised birthweight centile in the smoking group was 17.0 (0–78) compared to 55.5 (4–100) in the non-smoking group (P < 0.001). A causal relationship between elevated TX-M and IUGR could not be established.ConclusionsMaternal smoking in pregnancy is associated with altered eicosanoid production in favour of the vasoconstrictor thromboxane A2 which occurs early in the first trimester.

► This study looks at the effect of maternal smoking in pregnancy on eicosanoid production.
► It demonstrates that smoking in pregnancy is associated with altered eicosanoid production in favour of the vasoconstrictor thromboxane A2.
► However, there is no correlation between elevated maternal thromboxane A2 and the reduction in neonatal birthweight seen in pregnancies complicated by maternal smoking.