Discussion:
In the current multicentre collaborative study on 384 neonates with MAS,
347 were discharged home successfully. Previous studies have made
efforts to identify predictors of mortality 2,3. With
improved survival there is limited evidence on length of stay in the
hospital based on associated morbidities, although few studies have
addressed the predictors of severe MAS9-11. The
present collaborative study attempted to devise a predictive model/
scores to predict prolonged stay. To our knowledge, this is the first
study to determine the predictors of prolonged stay in the hospital in
MAS neonates.
The requirement of primary support beyond O2, FiO2 beyond 30% by 1 hour
of admission, moderate-severe PPHN and HIE stage 2 or 3 were predictive
of prolonged hospital stay (>7 days) in our cohort. The
final weighted score in the model was obtained from beta-coefficients
and is known to be superior to the traditional way of devising using
odds ratio18. The final score thus obtained from the
regression had excellent discriminatory power to predict the outcome
[AUC 0.82, 95% CI (78-87%)], figure 2. The optimal cutoff
(J-point) >21 with varying combinations of any of the 4
predictors had a positive predictive value of 2.6, i.e. 2.6 times more
likely to have prolonged hospital stay. The OSI was used to classify the
severity of PPHN in the study. The OSI, as evidenced in previous
studies, correlates with OI when SpO2>70% and is a
non-invasive reliable marker allowing for continuous monitoring for
oxygenation status15,19. The conventional definition
proposed by Cleary and Wiswell to define severity of MAS involves: (a)
mild MAS, requires <40% oxygen for <48 hours, (b)
moderate MAS, requires >40% oxygen for >48
hours with no air leak, and (c) severe MAS, requires assisted
ventilation for >48 hours and is often associated with
PPHN20. The conventional definition has been in use
for more than two decades. The severity is primarily based on
respiratory support and does not provide guidance on mortality or length
of stay in hospital. Moreover with the increasing use of CPAP as primary
support8 in the current era, the applicability of the
classification is a debatable. The index study identified additional
morbidities in the current era with better management of MAS and
moreover determined the predictive scores for prolonged stay.
The predictors of severe MAS had varied with previous two published
studies9-10. Hofer et al. studied 55 neonates with
severe MAS from a cohort of 205 MAS neonates and found acute tocolysis,
fetal distress and moderate birth asphyxia as significant risk factors
associated with severe MAS on univariate analysis. The independent
predictors by regression analysis were not available. The majority of
neonates had a long stay with a median stay of 12.5 (1-144) days.
Another retrospective cohort by Oliveira et al. enrolled 15 neonates
with severe MAS from a cohort of 29 MAS neonates and found the need for
surfactant therapy as a predictor of severity. These neonates had a
hospital stay of a median (range) of 8 (2-29) days. Previous studies
were limited by smaller samples and thus limited predictors of severity.
Although the length of stay was similar to the index study, predictors
of prolonged stay were not specifically addressed.
The associated morbidities in the current study were similar to other
published studies5, 9, 10-12 in MAS, except Oliveira
et al10 who had higher surfactant requirement in the
sample of 29 neonates. CPAP is increasingly used as the primary
respiratory support in MAS5,8. A randomized trial by
Pandita et al.5 evaluated the role of CPAP as primary
respiratory support in MAS and found a reduction in the need for
mechanical ventilation, sepsis, shock and PPHN in the CPAP group. CPAP
as primary respiratory support was used in 184 (53%) neonates with
invasive ventilation in 64 (19%) in our study. The current study also
had a lower incidence of late-onset sepsis in 2 (0.6%). Despite the use
of CPAP as primary support, there was no increased incidence of air
leaks compared to similar studies5, 8. Antibiotics are
commonly prescribed empirically in neonates with MAS owing to the
sickness. However, antibiotics have not affected the duration of
hospital stay or mortality in MAS as per meta-analysis of 4
RCTs22. The current study had 7 (2%) neonates with
early-onset sepsis and 2 (0.6%) neonates with late-onset sepsis.
However, antibiotics were started for 322 (93%) neonates empirically.
Considering the low incidence of sepsis, there is a need for quality
improvement strategies for optimizing antibiotic usage in MAS. Steroids
reduce pulmonary inflammation on histology and improve oxygenation in
animal studies23, 24. Two recently published
systematic reviews25, 26 have evaluated the role of
steroids in MAS. There was no mortality benefit, but reduced hospital
stay with nebulised budesonide was observed (low certainty of evidence).
The current study used dexamethasone in post-extubation settings, and
nebulised steroids or methylprednisolone were not used. There is a need
for further large well-designed study evaluating the role of steroids in
severe MAS.
The strengths of the study are large sample size from a multicentric
cohort, standardized criteria for respiratory management and devising a
simple clinical prediction score. Difference in the level of nursing
care, doctor:staff ratio, different patient demographics could have
altered outcomes in MAS at each centres. Despite these limitations, the
study has proposed a prediction score for a prolonged stay in MAS
applicable across low and middle-income countries. This scoring could
help in optimizing the strategies for treating MAS in the initial few
hours. Validation of the scoring would be required in different settings
before broader application of the scoring. The prediction score can
serve as a tool for risk stratification for future clinical trials.
There is a need for QI strategies on optimizing antibiotic use and
respiratory management. To conclude, more than two-thirds of neonates
with MAS had prolonged stay. The primary support beyond oxygen, Fio2
requirement >30%, Moderate to severe PPHN, HIE stage 2 or
3 were predictive of prolonged stay in neonates with MAS.