Addition of sildenafil citrate to hydration therapy may increase amniotic fluid index and improve obstetrical outcomes in women with idiopathic oligohydramnios
EBM Focus - Volume 12, Issue 17
- Limited information regarding management of oligohydramnios is available.
- The efficacy of adding sildenafil citrate (Viagra) 25 mg orally every 8 hours to hydration therapy to increase amniotic fluid index and improve obstetrical outcomes was investigated in an open-label randomized trial of 184 women with a singleton pregnancy (median 32.4 weeks gestation) with idiopathic oligohydramnios (amniotic fluid index < 5 cm).
- Median amniotic fluid index was increased in the sildenafil citrate group compared to the hydration alone group starting at 1 week after treatment and remained so after 6 weeks (11.5 cm vs. 5.35 cm, p = 0.02). Lower rates of cesarean delivery, 5-minute Apgar score < 7, umbilical artery pH < 7.2, and neonatal admission to the intensive care unit with sildenafil citrate were also observed.
Idiopathic oligohydramnios may be associated with an increased risk of emergency cesarean delivery for fetal distress, admission to a neonatal intensive care unit, and meconium aspiration syndrome compared to pregnancies with normal amniotic fluid index (AFI) (Ultrasound Obstet Gynecol 2017 Apr;49(4):442). Limited information regarding its management is available and options in the third trimester include maternal hydration (Cochrane Database Syst Rev 2002;(1):CD000134), fetal surveillance for signs warranting delivery (Clin Perinatol. 2011 Mar;38(1):33), and intrapartum amnioinfusion to reduce cord compression during labor (Obstet Gynecol 2000 Nov;96(5 Pt 2):861). A recent open-label randomized trial investigated the effect of adding sildenafil citrate to hydration therapy on AFI and obstetrical outcomes in 184 women (mean age 30 years) with a singleton pregnancy (median 32.4 weeks gestation) with idiopathic oligohydramnios (AFI < 5 cm). The women were randomized to hydration therapy plus sildenafil citrate 25 mg orally every 8 hours vs. hydration therapy alone until delivery. Hydration therapy consisted of IV infusion of 2 L of isotonic solution over 4 hours once, with a repeat infusion if there was < 20% increase in AFI after 24 hours, and instructions to drink 2 L of fluid daily after discharge. The primary outcome, AFI, was determined by one ultrasonographer blinded to treatment allocation at twice weekly outpatient assessments.
The median AFI was increased in the sildenafil citrate group compared to the hydration only group starting at 1 week after treatment and remained so after 6 weeks (11.5 cm vs. 5.35 cm, p = 0.02). Pregnancy was prolonged in the sildenafil citrate group with delivery occurring at a median gestational age of 38.3 weeks vs. 36 weeks (p = 0.001). In addition, there were lower rates of adverse obstetrical outcomes in the sildenafil citrate group with cesarean delivery in 28% vs. 72.6% (p = 0.001, NNT 3), 5-minute Apgar score < 7 in 9.8% vs. 31% (p = 0.001, NNT 5), umbilical artery pH < 7.2 in 7.3% vs. 20.2% (p = 0.016, NNT 8), meconium staining in 13.4% vs. 56% (p = 0.001, NNT 3), and neonatal admission to the intensive care unit in 11% vs. 41% (p = 0.001, NNT 4).
The results of this trial suggest that the addition of sildenafil citrate to hydration therapy increases the AFI and improves obstetrical outcomes. The reduced rates of adverse obstetrical outcomes are difficult to interpret. The rate of cesarean section was much higher in the hydration only group and may have partially resulted from a lower threshold by the obstetricians to intervene in the women with a low AFI, particularly since the study was not blinded and well defined criteria for the induction of labor or use of cesarean section were not stated. The higher rates of adverse neonatal outcomes may be partly due to the lower gestational age of the neonates in the hydration only group (which itself may reflect the increased rates of iatrogenic pre-term delivery). In addition, the clinical significance of the increased rates of meconium staining is unclear as the rates of meconium aspiration syndrome were not reported. In summary, sildenafil citrate may increase the amniotic fluid index, but additional studies that account for the potential influence of delivery management are needed to evaluate its clinical benefit in women with idiopathic oligohydramnios.