Umbilical cord serum levels of thromboxane B2 in term infants of women who participated in a Placebo-Controlled trial of low-dose aspirin

Abstract

Objective: Our aim was to quantify thromboxane B2 (TXB2) in umbilical cord serum of term infants of nulliparous, low-risk women who were randomly assigned to either placebo or low-dose (60 mg) aspirin (ASA) on a daily basis from 24 weeks' gestation through delivery as part of a randomized clinical trial for prevention of preeclampsia.

Methods: Umbilical cord sera from 230 singleton, term infants whose mothers were involved in our low-dose ASA trial were assayed for TXB2, the stable metabolite of thromboxane A2, without knowledge of treatment or outcome data. The data were related to assigned treatment group, longitudinal pattern of maternal serum TXB2 levels, and other maternal and newborn characteristics. The data also were analyzed according to whether or not maternal serum levels of TXB2 at 29–31, 34–36, and delivery were reduced ≥50% compared to values prior to initiation of the trial.

Results: Umbilical cord TXB2 levels (ng/ml, mean ± SE) were significantly lower at term in the ASA group (36.1 ± 3.3, n = 111) than in the placebo group (56.6 ± 5.7, n = 119; P = 0.002). Umbilical cord TXB2 levels were correlated to those in maternal serum at delivery in the ASA group (r = 0.3441; P = 0.0005) but not in the placebo group (r = 0.0626; P = 0.53). Regardless of assigned treatment group, infants whose mothers had a <50% longitudinal reduction in serum TXB2 had lower umbilical cord TXB2 levels (39.2 ± 3.6, n = 114) than infants whose mothers had < 50% reductions in TXB2 (54.6 ± 5.9, n = 116; P = 0.027). Birthweights of these infants correlated inversely (r = -0.1678, P = 0.017) with maternal serum TXB2 at delivery but not to umbilical cord TXB2 levels; the best correlation between birthweight and maternal serum TXB2 was noted in pregnancies assigned to receive placebo (r = -0.2558, P = 0.009).

Conclusions: Umbilical cord serum levels of TXB2 1) are reduced in instances of long-term maternal ingestion of ASA, 2) correlate well with maternal serum levels of TXB2 at delivery when there is evidence for consistent maternal use of ASA, but 3) do not correlate with maternal serum TXB2 levels when there is no evidence for frequent maternal ingestion of cyclooxygenase inhibitors. These data suggest that the capacity for platelet production of TXA2 in fetal and maternal compartments are regulated independently. Finally, there is an inverse relationship between maternal serum TXB2 levels at delivery and birthweight of newborn infants that is most evident among the pregnancies assigned to placebo and also among pregnancies in which there was little evidence to suggest a pattern of cyclooxygenase inhibitor use during pregnancy.

Key Words:

• aspirin
• newborn infant
• serum thromboxane B2
• fetal growth