Effect of sildenafil administered in utero on Neurodevelopmental growth of children at 2 years

Severe early-onset fetal growth restriction (FGR) is associated with stillbirth, neonatal death, and neurodevelopmental impairments. Although poor maternal spiral artery remodelling preserves vasoactive responsiveness, it can be treated with the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil, which may lead to better perinatal outcomes.

The current superiority, double-blind randomised controlled trial investigated the effects of sildenafilon perinatal outcomes in 135 women with pregnancies affected by FGR.

The recruited women received either sildenafil (25 mg three times daily) or a placebo until delivery or up to 32 weeks of gestation. The primary outcome measured was survival without cerebral palsy or neurosensory impairment, or a Bayley-III composite score greater than 85, with assessments conducted at 2 years of age.

The findings of the study revealed:

·        No significant improvement was observed in time to delivery or overall perinatal outcomes with sildenafil. 

·        Out of the 135 women, 75 infants (55.5%) were discharged alive, and follow-up was possible for 61 infants. 

·        In addition, the study found no differences in neurodevelopmental outcomes or blood pressure between the two groups.

·        However, infants who received sildenafil had a larger head circumference at 2 years compared to those who received placebo.

Thus, the study concluded that sildenafil did not prolong pregnancy or improve perinatal outcomes and did not enhance neurodevelopment in FGR survivors, recommending against its use for this condition.

Source:Sharp A, Cornforth C, Jackson R, Harrold J, Turner MA, Kenny LC, Baker PN, Johnstone ED, Khalil A, von Dadelszen P, Papageorghiou AT, Alfirevic Z, Vollmer B; STRIDER group. Neurodevelopmental outcomes at 2 years in children who received sildenafil therapy in utero: The STRIDER randomised controlled trial. BJOG. 2024 Nov;131(12):1673-1683. doi: 10.1111/1471-0528.17888. Epub 2024 Jun 25. PMID: 38923115.