FROM OBSTETRICS & GYNECOLOGY
Treatment with oral sildenafil citrate significantly extended gestation by 4 days, compared with placebo in women with preeclampsia in a randomized trial.
The findings come from one of a trio of studies looking at efforts to improve outcomes for women with preeclampsia, which were published online July 11 in Obstetrics & Gynecology.
“We hypothesized that the potential increase in in utero placental and fetoplacental blood flow with the use of sildenafil citrate may be associated with pregnancy prolongation (the primary study outcome) and improved maternal and perinatal outcomes,” wrote Alberto Trapani Jr., MD, PhD, of Hospital of Federal University of Santa Catarina, Florianopolis, Brazil, and his colleagues (Obstet Gynecol. 2016;128:253-259. doi: 10.1097/AOG.0000000000001518 ).
The researchers randomized 93 singleton pregnancies with preeclampsia at 24 to 33 weeks’ gestation to receive 50 mg oral sildenafil citrate (47 patients) or a placebo (46 patients) every 8 hours. Baseline characteristics were similar between the two groups.
Overall, pregnancies lasted an average of another 14.4 days in the sildenafil group, compared with 10.4 days in the placebo group. Additionally, the percent reduction in the pulsality indices of both uterine arteries and umbilical arteries were significantly higher in the sildenafil group, compared with the placebo group (22.5% vs. 2.1% and 18.5% vs. 2.5%, respectively). Maternal blood pressure before and 24 hours after randomization was lower with sildenafil. Incidence of adverse effects, perinatal morbidity, and mortality were similar between the two groups.
“These results, combined with the results of other studies, are promising,” although larger studies with earlier treatment initiation are needed, the researchers wrote. Evaluation of other phosphodiesterase type 5 inhibitors also may be useful in treating preeclampsia, they noted. Dr. Trapani and his colleagues reported having no financial conflicts.
Two other studies published in the same issue of Obstetrics & Gynecology focused on using biomarkers to help predict delivery times in women with suspected preeclampsia.
Any one of several single angiogenesis-related biomarkers can be a useful diagnostic test for preeclampsia, wrote Suzy Duckworth, MBBS, of King’s College London and her colleagues. In a prospective, observational study of 423 women with suspected preeclampsia, the researchers found that a combination of biomarkers including placental growth factor (PlGF) was not significantly better than PlGF alone (receiver operating curve area of 0.90 and 0.87, respectively) for predicting preeclampsia requiring delivery within 14 days. Two other single markers, soluble fms-like tyrosine kinase-1 (sFlt-1) and endoglin, yielded similar results; each demonstrated a receiver operating curve area of 0.83.
“It is currently difficult to distinguish preeclampsia of a severity that requires early delivery from other less serious phenotypes,” the researchers wrote. “An accurate biomarker (or panel of biomarkers) to enable prognosis of perinatal complications could have a substantial effect on management strategies, with the aim of minimizing adverse maternal and fetal outcomes,” they wrote (Obstet Gynecol. 2016;128:245-252. doi: 10.1097/AOG.0000000000001508 ).
Dr. Duckworth had no financial conflicts to disclose, but several of her coauthors disclosed relationships with pharmaceutical companies and one coauthor is a minority shareholder in Metabolomic Diagnostics, a company with an interest in preeclampsia biomarkers.
In another study including 1,041 women with suspected preeclampsia, those with a sFlt-1:PlGF ratio greater than 38 were nearly three times as likely to deliver on the day of the test than women with an sFlt-1:PlGF ratio of 38 or less, wrote Harald Zeisler, MD, of Medical University Vienna and his colleagues (Obstet Gynecol. 2016;128:261-269. doi: 10.1097/AOG.0000000000001525 ).
Women with an sFlt-1:PlGF ratio greater than 38 also had significantly shorter remaining times to delivery than women with an sFlt-1:PlGF ratio of 38 or less (median 17 days vs. 51 days). The study was a secondary analysis of an observational cohort study of women aged 18 years and older from 24 to 36 6/7 weeks’ gestation.
In a preterm birth analysis of 848 women, 71% of the 184 women with an sFlt-1:PlGF ratio greater than 38 had a preterm delivery, compared with 18% of the 664 women with an sFlt-1:PlGF ratio of 38 or less.
The future clinical use of the sFlt-1:PlGF ratio “may potentially assist in informing the health care team of an impending risk to the mother, fetus, or both that may require further assessment and medical intervention,” the researchers wrote.
Dr. Zeisler and several coauthors disclosed relationships with multiple companies, including Roche Diagnostics, which sponsored the study.