Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin on length of stay in the neonatal intensive care unit

BACKGROUND: Preeclampsia is a major pregnancy complication with adverse short- and long-term implications for both the mother and baby. Screening for preeclampsia at 11-13 weeks' gestation by a combination of maternal demographic characteristics and medical history with measurements of biomarkers can identify about 75% of women that develop preterm-preeclampsia with delivery at <37 weeks' gestation and 90% of those with early-preeclampsia at <32 weeks, at a screen positive rate of 10%. A recent trial (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) has reported that in women identified by first-trimester screening as being at high-risk for preeclampsia, use of aspirin (150 mg/day from the first to the third trimester), compared to placebo, reduced the incidence of preterm-preeclampsia, which was the primary outcome, by 62% (95% confidence interval, 26-80%) and the incidence of early-preeclampsia by 89% (95% confidence interval, 53-97%). The surprising finding of the trial was that despite the reduction in preeclampsia the incidence of admission to the neonatal intensive care unit, which was one of the secondary outcomes, was not significantly affected (odds ratio 0.93, 95% confidence interval, 0.62-1.40). OBJECTIVE: To examine the effect of prophylactic use of aspirin during pregnancy in women at high-risk of preeclampsia on length of stay in the neonatal intensive care unit. STUDY DESIGN: This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial to assess evidence of differences in the effect of aspirin on length of stay in neonatal intensive care. Bootstrapping was used for the comparison of mean length of stay between the aspirin and placebo groups. Logistic-regression was used to assess treatment effects on stay in the neonatal intensive care unit. RESULTS: In the trial there were 1620 participants and 1571 neonates were liveborn. The total length of stay in neonatal intensive care was substantially longer in the placebo than aspirin group (1696 vs. 531 days). This is a reflection of significantly shorter mean lengths of stay in babies admitted to the neonatal intensive care unit from the aspirin than the placebo group (11.1 vs. 31.4 days; a reduction of 20.3 days (95% confidence interval, 7.0-38.6; p=0.008). Neonatal intensive care of babies born at <32 weeks' gestation contributed 1856 (83.3%) of the total of 2227 days in intensive care across both treatment arms. These occurred in 9 (1.2%) of the 777 livebirths in the aspirin group and in 23 (2.9%) of 794 in the placebo group (odds ratio 0.42; 95% confidence interval, 0.19-0.93; p=0.033). Overall, in the whole population, including zero lengths of stay for those that were not admitted to the neonatal intensive care unit, the mean length of stay was longer in the placebo than aspirin group (2.06 vs 0.66 days; reduction of 1.4 days (95% confidence interval, 0.45-2.81; p=0.014). This corresponds to a reduction in length of stay of 68% (95% confidence interval, 20-86%). CONCLUSIONS: In pregnancies at high-risk of preeclampsia administration of aspirin reduces the length of stay in the neonatal intensive care unit by about 70%. This reduction could essentially be attributed to a decrease in the rate of births at <32 weeks' gestation, mainly because of prevention of early preeclampsia. The findings have implications for both short- and long-term healthcare costs as well as infant survival and handicap.