2 Methods
A retrospective cohort study was conducted with patients registered in
the Neonatal Database of a Brazilian tertiary hospital, born in the
years 2016 to 2020 (5 years), with gestational ages between 23 and 30
weeks and birth weight between 401 and 1250 g.
Newborns with complex congenital heart disease diagnoses, major lung
malformations, and deaths before 28 days of life were excluded from the
study.
The analyzed antenatal variables consisted of maternal systemic arterial
hypertension (chronic or pregnancy-induced arterial hypertension, with
or without edema and proteinuria), maternal smoking, chorioamnionitis
(considered through clinical or laboratory criteria: maternal
leukocytosis, with no other identifiable infectious focus that would
justify it), and use of antenatal corticosteroids (betamethasone,
complete and incomplete cycles). The analyzed postnatal variables were
gestational age (GA), birth weight in grams (BW), gender (male or
female), adequacy for gestational age using Intergrowth-21st curves12, with birth weight below the 10th percentile for
gestational age classified as small for gestational age (SGA), and birth
weight above the 90th percentile classified as large for gestational age
(LGA), need for surfactant, patent ductus arteriosus (clinical or
echocardiographic diagnosis), early sepsis (clinical-laboratory criteria
with the use of antibiotics for at least five days, starting up to the
3rd day of life), late sepsis up to the 14th day of life
(clinical-laboratory criteria with the use of antibiotics for at least
five days, starting after the 3rd day of life), necrotizing
enterocolitis, defined using the Bell Criteria 13, and
respiratory support and fraction of inspired oxygen (FiO2) on the 14th
day of life.
Respiratory support was characterized as nasal oxygen catheter (simple
or high-flow nasal catheter), nasal continuous positive airway pressure
(CPAP) or non-invasive intermittent positive pressure ventilation
(NIPPV), conventional invasive mechanical ventilation (MV), and
high-frequency ventilation (HFV).
The evaluated FiO2 and respiratory support were the most frequently
recorded on the day (higher needs that occurred transiently were
discarded). The type of ventilation device and its manufacturer were not
considered.
The analyzed outcomes were defined by the presence of bronchopulmonary
dysplasia and their classifications, made according to the definitions
of the National Heart, Lung and Blood Institute (NHLBI) in 2000: no
bronchopulmonary dysplasia, mild bronchopulmonary dysplasia (patients
requiring supplemental oxygen with 28 days of life or more but not at 36
weeks corrected gestational age), moderate bronchopulmonary dysplasia
(Patients requiring supplemental oxygen at 28 days of age and
maintaining a FiO2 requirement of less than 30% at 36 weeks of
corrected gestational age), and severe bronchopulmonary dysplasia
(patients in need of supplemental oxygen at 28 days of life and
maintaining the need for FiO2 higher than or equal to 30% or positive
pressure at 36 weeks of corrected gestational age)14,15.
The associations between the factors of interest and BPD and their
classifications were made by adjusting single and multiple
log-multinomial regression models, obtaining crude and adjusted relative
risks (RRaj), and using gestational age and antenatal corticosteroids as
covariates. The software SAS 9.4 was used.
For the elaboration of the predictive instruments, the database was
randomly divided into a training sample (70%), used for the elaboration
of the moderate and severe BPD prediction equations, and the rest of the
sample (30%) was used for validation.
For the instrument’s construction, respiratory supports were classified
into three categories: none, use of nasal oxygen catheter/CPAP/NIPPV,
and conventional mechanical/high-frequency ventilation.
Four strategies were proposed for building the equations, as described
in table 1. Thus, the probabilities of BPD were obtained, considering
moderate and severe degrees versus mild and null, thus being a binary
variable. A logistic regression model allowed each of the four variable
selection strategies to result in BPD prediction probabilities (p).
The equations were obtained from the training sample and validated in
the validation sample; that is, the probabilities were obtained from the
data of the last-mentioned sample, from which the probability of BPD was
also calculated using the NICHD instrument currently used in that
institution. During validation, patients on an O2 catheter had FiO2
values classified as 29%; the entire sample was considered ”Hispanic”
regarding ethnicity when using the NICHD instrument.
The results were compared with the actual status of the sample for BPD
(confusion matrix), and then sensitivity, specificity, and predictive
values were calculated. Kappa indices were calculated to compare the
results obtained by the equations with those obtained by the NIHCD
method, obtaining agreement between the methods, given that none of the
methods can be considered a gold standard.
The project received ethical approval from the Institution’s Human
Research Ethics Committee of the Ribeirão Preto Medical School (CEP
FMRP), Opinion number: 1.903.783/CAAE 63764517.4.0000.5505).