Results
A total of 729 patients were recruited: 319 in the Theophylline group
and 410 in the non-Theophylline group.
Tables 1 and 2 summarize the two groups’ baseline characteristics. No
differences were found in sociodemographic variables, but significant
clinical differences were identified, being infants in Theophylline
group more fragile (less GA at birth and at KMCP entry, less weight at
birth and at entry, more hospital stay, and less non-invasive
ventilation).
Table 3 describes the follow-up results. The Theophylline group had more
BPD defined as OD >28 days and GA ≧ 36 weeks, but when BPD
was defined as OD >28 days and GA ≧40 weeks, there was no
difference between groups18. Infants who received
Theophylline had a higher frequency of apneas during the hospital stay
and ambulatory follow-up. Additionally, chronological age at oxygen
weaning and weight at 40 weeks were higher than in the non-Theophylline
group. Although the feeding pattern at oxygen weaning was similar
between the two groups, the non-Theophylline group had a higher
proportion of exclusive breast milk (EBM) at 40 weeks (46 vs 36%).
No differences were found in the number of readmissions up to 40 weeks.
Neither in the frequency of intraventricular hemorrhage (IVH),
retinopathy of prematurity (ROP) or neurodevelopmental problems.
Regarding the possible side effects associated with Theophylline
treatment, we found no differences in GER or gastrointestinal disorders.
However, more tachycardia episodes were recorded in the Theophylline
group (1.3% vs 0).
Finally, patients in the Theophylline group had a higher percentage of
losses (3.5% vs 1%), although in general, these were minor for the two
cohorts.
In order to adjust for baseline differences between groups (GA, birth
weight, GA at study recruitment, frequencies of IUGR and apnea, days in
NICU and days with oxygen at study recruitment), we performed propensity
score matching. Then, multiple linear regression with total days of
oxygen dependency as the outcome variable and having received
Theophylline as the exposure variable. The control variables were
frequency of EBF at O2 weaning, days of mechanical ventilation, weight
at study recruitment, weight gain between study recruitment and oxygen
weaning and weight reached at oxygen weaning. Probable interactions were
entered, and model diagnostics were performed (after individual
evaluation, 6 outliers were excluded).
Tables 4 and 5 show the propensity score matching and multiple linear
regression analysis. After adjusting for baseline differences between
groups with propensity score matching, it was found that controlling for
days of mechanical ventilation, weight at study recruitment and weight
gain to reach the oxygen weaning weight (Figure 1), EBF could reduce
oxygen dependency in 9 days; on the other hand, for each day with
mechanical ventilation, oxygen dependency increases in 2 days. No effect
of Theophylline administration was found between the two groups (682
observations, R2 0.63, 95% CI (-1.01, 4.66) p=0.21).