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.