Discussion
In our study there was a higher combined outcome of death or CLD in porcine compared to bovine groups [48 (30%) vs 20 (13%), OR:2.7; 95% CI:1.5-4.8; p=0.001]. This finding is unlike Cochrane review which found lesser mortality (in-hospital) in porcine group. Cochrane Meta-analysis done by Singh et.al. demonstrated a significant increase in death or oxygen requirement at 36 weeks’ postmenstrual age (typical RR 1.30, 95% CI 1.04 to 1.64; typical RD 0.11, 95% CI 0.02 to 0.20; NNTH 9, 95% CI 5 to 50; 3 studies and 448 infants; moderate quality evidence) in bovine group compared to porcine group.7Systematic review by Tridente et.al. shows a trend favouring porcine groups as well4. In this review, 12 trials reported data on the composite BPD/mortality outcome, analysing poractant-α given at a dose of 200 mg/kg and another study evaluating poractant-α at a dose of 100mg/kg which showed significantly. The concept CLD has evolved over a period of time with changing definitions based on the pathophysiological understanding of the condition. Even after the widely used NICHD workshop definition which is used in our study, modifications are ongoing. 6,18-25 This finding is unlike Cochrane review which found lesser mortality (in-hospital) in porcine groups. Cochrane Meta-analysis done by Singh et.al. demonstrated a significant increase in death or oxygen requirement at 36 weeks’ postmenstrual age (typical RR 1.30, 95% CI 1.04 to 1.64; typical RD 0.11, 95% CI 0.02 to 0.20; NNTH 9, 95% CI 5 to 50; 3 studies and 448 infants; moderate quality evidence) in bovine group compared to porcine group.6 Systematic review by Tridente et.al. shows a trend favouring porcine groups as well4. In this review, 12 trials reported data on the composite BPD/mortality outcome, analysing poractant-α given at a dose of 200 mg/kg and another study evaluating poractant-α at a dose of 100mg/kg which showed significantly lower incidence in neonates treated with 200 mg/kg poractant-α (p < 0.001), and pooling together neonates treated with both doses (p < 0.001) compared to bovine surfactant.4 The review by Luna et.al. which compares RWE and RCTs showed that the composite endpoint of BPD or death occurred with similar incidence in the beractant and poractant alfa groups in the two studies with RWE that reported this outcome.5,9-12
Moderate-Severe BPD, were more common among babies which received Porcine surfactant. This was unlike Cochrane review where no difference was found and in contrast to Tridente et.al. meta-analyses.6,4 This could be due to the babies which received Porcine surfactant being smaller babies with average GA of 28 weeks compared with those who received bovine surfactant with average GA of 30 weeks (p<0.001), which inherently increases the chances of having BPD of any severity. This observation can also be seen to be coherent with the subgroup analysis of infants>28 weeks, which does not show a statistically significant difference in case of Moderate-Severe BPD. A real-world study by Paul S et.al. that compared the incidence of BPD with beractant and poractant alfa found no significant difference between treatments.11
In our study, the need for redosing of surfactant in RDS was not different between porcine and bovine surfactant in their standard initial dose (p=0.2). Subgroup analysis of infants of >28 weeks as well as individual surfactants did not show any difference(p=0.1). This is in contradiction with the meta-analyses by Tridente et.al.4 where redosing was needed more often in the bovine group than in the porcine group with a statistically highly significant difference (p=0.001). The said study also concludes that the effect on the need for redosing is greater at higher gestational ages unlike what we found in our study. This could be likely attributed to the usage of studies well from 3 decades back when the supportive care for preterm babies who might have RDS was not standardised compared to the present day. Lanciotti L et.al. noted that if poractant alfa is used, need for re-dosing can be minimised by using a larger initial dose of 200 mg/ kg. For other surfactants, such data are not available.8 As per The Cochrane review by Singh et.al. , significant increase in the incidence of ’receiving > 1 dose of surfactant’ was noted in infants treated with modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract. Clinical equivalence was noted with no significant differences in comparative trials between bovine lung lavage surfactant and modified bovine minced lung surfactants.7
In our study there was no difference in the duration of CPAP needed as well as Invasive ventilation needed (p=0.06 and p=0.6 respectively). Length of hospital stay was more in babies which received porcine surfactant (p<0.001). This may be due to the fact that porcine group babies compared to bovine groups were of a lower gestational age (28 weeks vs 30 weeks) and lower birth weight (1113 grams vs 1443 grams).
In our study we did not find any statistically significant difference for any pulmonary air leaks like Pneumothorax(p=1). This is in line with Cochrane review7 but contrasts Tridente et.al. study4 which concludes less chances of Air leak among porcine surfactant use. This could be due to understanding that the occurrence of air leaks may be more attributable to the lung tissue, sepsis, ventilatory strategies than the surfactant.
The occurrence ROP requiring LASER was similar in both bovine and porcine groups in our study(p=0.6). As per Cochrane review as well, no significant difference was found between surfactant preparations and occurrence of ROP needing LASER.7
PDA requiring treatment was noted to be more in porcine group (24%) compared to bovine group (12%) which was statistically significant (p=0.006). However, Cochrane reported no effect of surfactant preparation on risk of PDA requiring treatment with cyclooxygenase inhibitor or surgery.7 In a study by Mussavi et.al. it was noted that in neonates over 32 weeks there was a significant difference between groups for the incidence rate of PDA (P = 0.011) but not below 32 weeks.15 The smaller the gestation, the more chances of having a PDA needing treatment due to inherent prematurity related factors probably explains the occurrence in our study.
The study did not find a statistically significant difference between bovine and porcine groups with respect to IVH (of any grade) and more importantly IVH of Grade 3 or more. The Cochrane review also did not show demonstrable significant difference among the surfactant preparations on the risk of IVH (of any grades) as well as severe IVH of Grade 3 or more.7
The incidence of NEC in our study was no different than among bovine and porcine groups (p=0.6). Even the Cochrane review does not show any difference between the surfactant preparations with respect to occurrence of NEC of any stage.7 In a study by Najafian et.al. they found that intraventricular haemorrhage (IVH) and necrotizing enterocolitis (NEC) are more frequent in the Curosurf group in comparison with Survanta in 29-32 weeks neonates. It was also realised that lower birth weight and lower gestation were associated with more complication in both groups.16
We chose retrospective data from December 2022 backwards to August 2019 as it was after an Update by European Consensus Guidelines on management of RDS1 had been published and widely being discussed and adopted in our Neonatal units. A sub-group analysis of neonates > 28 weeks was chosen because these were babies who were candidates for less RDS, less CLD (or BPD) and other morbidities compared to those ≤ 28 weeks. Also, there was an inclination towards porcine surfactant by some clinicians in ≤ 28 weeks based on European consensus guidelines. Alongside subgroup analysis was done with all the 3 commercially available surfactants in India.