Porcine versus bovine surfactant therapy for RDS in preterm neonates: pragmatic meta-analysis and review of physiopathological plausibility of the effects on extra-pulmonary outcomes

Abstract

Background: While porcine seems to be superior to bovine surfactants in terms of respiratory outcomes, it is unclear if a surfactant can improve extra-pulmonary outcomes in preterm neonates with respiratory distress syndrome and if there is any physiopathological/biological mechanism linking surfactant therapy to these outcomes. We aim to fill these knowledge gaps. Methods: Systematic and pragmatic review coupled with meta-analysis of randomized controlled trials of bovine or porcine surfactants administered to treat RDS in preterm neonates; common extra-pulmonary neonatal intensive care outcomes were considered. As additional analysis, animal or human translational studies about mechanisms linking surfactant replacement to extra-pulmonary neonatal outcomes were also systematically reviewed. Results: Porcine surfactant is associated with lower incidence of patent ductus arteriosus (OR:0.655; 95%CI:0.460-0.931); p = 0.018; 12 trials; 1472 patients); prenatal steroids (coeff.:-0.009, 95%CI:-0.03-0.009, p = 0.323) and gestational age (coeff.:0.079, 95%CI:-0.18-0.34, p = 0.554) did not influence this effect size. No significant differences were found between porcine and bovine surfactants on neonatal intensive care unit length of stay (mean difference (days):-2.977; 95%CI:-6.659-0.705; p = 0.113; 8 trials; 855 patients), intra-ventricular hemorrhage of any grade (OR:0.860; 95%CI:0.648-1.139); p = 0.293; 15 trials; 1703 patients), severe intra-ventricular hemorrhage (OR:0.852; 95%CI:0.624-1.163); p = 0.313; 15 trials; 1672 patients), necrotizing entero-colitis (OR:1.190; 95%CI:0.785-1.803); p = 0.412; 9 trials; 1097 patients) and retinopathy of prematurity (OR:0.801; 95%CI:0.480-1.337); p = 0.396; 10 trials; 962 patients). Conclusions: Physiopathological mechanisms explaining the effect of surfactant have been found for patent ductus arteriosus only, while they are lacking for all other endpoints. Porcine surfactant is associated with lower incidence of PDA than bovine surfactants. As there are no differences in terms of other extra-pulmonary outcomes and no physiopathological plausibility, these endpoints should not be used in future trials. Registration: PROSPERO n.CRD42018100906.

Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia

“…PORα is a widely available surfactant obtained by minced porcine lung and considered to be the most efficacious in neonatal critical care, according to evidence based data and European guidelines 56 , 57 . It was purchased from Chiesi Farmaceutici S.p.A. (Parma, Italy), lyophilized and stored at − 80 °C until use.…”

Surfactant therapies for pediatric and neonatal ARDS: ESPNIC expert consensus opinion for future research steps

“…In time, our knowledge about exogenous surfactant has increased and now we know that not all surfactant preparations are equal. Phospholipid profile and protein content are important for the clinical efficacy in neonates with RDS [ 26 , 93 ], and it is likely that these characteristics would be relevant also in patients with PARDS and NARDS [ 23 ].…”

Surfactant use in late preterm infants: a survey among Belgian neonatologists

“…For instance, a tendency to overtreat extremely low birth weight neonates and a trend to undertreat neonates > 28 weeks GA has been reported in France and in Italy [ 24 , 25 ]. A specific action to avoid under- or overtreating is to carefully weigh each infant prior to surfactant administration [ 26 ]. If however surfactant is required before the baby’s birth weight is known (surfactant for early rescue therapy), it is acceptable to use whole vial dosing based on an estimated weight [ 9 ].…”