Efficacy and safety of surfactant replacement therapy for preterm neonates with respiratory distress syndrome in low- and middle-income countries: a systematic review

Abstract

Surfactant replacement therapy (SRT) has been shown to reduce mortality and air leaks in preterm neonates from high-income countries (HICs). The safety and efficacy of SRT in low- and middle- income countries (LMICs) have not been systematically evaluated. The major objectives of this review were to assess the (1) efficacy and safety, and (2) feasibility and cost effectiveness of SRT in LMIC settings. We searched the following databases—MEDLINE, CENTRAL, CINAHL, EMBASE and WHOLIS using the search terms 'surfactant' OR 'pulmonary surfactant'. Both experimental and observational studies that enrolled preterm neonates with or at-risk of respiratory distress syndrome (RDS) and required surfactant (animal-derived or synthetic) were included. A total of 38 relevant studies were found; almost all were from level-3 neonatal units. Pooled analysis of two randomized controlled trials (RCTs) and 22 observational studies showed a significant reduction in mortality at the last available time point in neonates who received SRT (relative risk (RR) 0.67; 95% confidence interval (CI) 0.57 to 0.79). There was also a significant reduction in the risk of air leaks (five studies; RR 0.51; 0.29 to 0.90). One RCT and twelve observational studies reported the risk of bronchopulmonary dysplasia (BPD) with contrasting results; while the RCT and most before-after/cohort studies showed a significant reduction or no effect, the majority of the case-control studies demonstrated significantly higher odds of receiving SRT in neonates who developed BPD. Two studies—one RCT and one observational—found no difference in the proportion of neonates developing pulmonary hemorrhage, while another observational study reported a higher incidence in those receiving SRT. The failure rate of the intubate-surfactant-extubate (InSurE) technique requiring mechanical ventilation or referral varied from 34 to 45% in four case-series. No study reported on the cost effectiveness of SRT. Available evidence suggests that SRT is effective, safe and feasible in level-3 neonatal units and has the potential to reduce neonatal mortality and air leaks in low-resource settings as well. However, there is a need to generate more evidence on the cost effectiveness of SRT and its effect on BPD in LMIC settings.

Optimal Ventilation and Surfactant Therapy in Very-Low-Birth-Weight Infants in Resource-Restricted Regions

“…SRT is the core of RDS management [4]. In RRR, SRT with nCPAP is safe and efficacious [20] and decreases mortality by 25% [21]. SRT, via less invasive methods, is widely used on a global scale.…”

Incidence and Outcome of Surfactant Therapy in Premature Neonates in ICU of KAMC

“…The results in this study have proven that the mortality was very low among premature subjects and majority of them were improved and shifted from ICU which support the study conducted by during 23 and 34 weeks gestational aged premature neonates but it was not agreed by the findings of Sankar et al, (2016) who found no difference in the risk of mortality in one of their randomized control trial. This study divulged that early administration of surfactant plays an important role in the prognosis of premature neonates with surfactant replacement therapy.…”

Challenges Faced in Translating the Benefits of Surfactant Replacement Therapy to a Resource-Limited Setting

“…Sankar et al in a systematic review of the efficacy and safety of SRT in preterm infants with RDS in low-and middle-income countries have concluded that SRT is safe, effective, and feasible in level III neonatal units and has the potential to decrease mortality. 20 In order for this to be realized, however, solutions to affordability and accessibility of surfactant, mechanical ventilators, CPAP machines, and neonatal intensive care measures would have to be devised.…”