A retrospective study, from 1997 to 2011, was performed at our center, a level III NICU, referral center for cardiac and surgical patients for the north of Portugal, with an average of 450 admissions per year, including about 50 VLBW infants. Preterms with birth weight less than 1500
g were included in the study. Newborns affected of major congenital anomalies, a TORCH infection, hydrops fetalis, and chromosomal anomalies, as well as the outborns and those transferred to other NICUs before 36 weeks of corrected gestational age, were excluded.
Clinical records were reviewed; demographics, histological chorioamnionitis and clinical data were assessed: gender, gestational age, birth weight, antenatal steroids pulses, delivery mode, respiratory support in the delivery room, Apgar score, the presence of RDS, the need for exogenous surfactant administration and mode of administration; respiratory support in the NICU, the need for oxygen therapy, the prevalence of BPD and other major morbidities (nosocomial sepsis, necrotizing enterocolitis, severe intraventricular hemorrhage, retinopathy of prematurity, patent ductus arteriosus, periventricular leukomalacia), and length of NICU stay and survival.
Antenatal steroid regimen was performed with dexamethasone (total dose of 24
mg, divided into two doses given intramuscularly every 12 hours) until 2003, and with betamethasone (24
mg, divided into two doses given intramuscularly 24 hours apart) thereafter, in pregnancies with threatened preterm labour below 35 weeks gestation.
Gestational age (in this study we considered the completed weeks) was assessed by menstrual age (women with regular menstrual cycles), ultrasound examination (when a discrepancy of two or more weeks existed between the age derived by menstrual dating and the age derived sonographically, or in the absence of a menstrual date) [10
], or the New Ballard Score (in the absence of obstetrical indexes) [11
]. Small for gestational age was defined as a birth weight below 10th centile of Lubchenco's fetal growth charts before 2003 [12
] and a birth weight below 10th centile of Fenton's fetal growth charts after 2003 [13
Early NCPAP is usually started immediately (first 15 minutes) after birth, although, in this study, it was considered when started in the first 30 minutes of life, once some patients were transported to the NICU, monitorized, and in spontaneous breathing. The first and 5th minute Apgar scores were dichotomized in two groups (≤7 and ≥8). RDS diagnosis was made on a combination of clinical and radiographic features according to the criteria of RDS of the Vermont Oxford Network: (1) PaO2
mmHg in room air, central cyanosis in room air, a requirement for supplemental oxygen to maintain PaO2
mmHg or a requirement for supplemental oxygen to maintain a pulse oximeter saturation over 85% within the first 24
h of life; and (2) a chest radiograph consistent with RDS (reticulogranular appearance to lung fields with or without low lung volumes and air bronchograms) within the first 24
h of life. The diagnosis of BPD was made in preterm newborns with gestational age 32 weeks or below, if the infant was chronically oxygen dependent at 36 weeks of corrected age and had a characteristic chest radiograph. In newborns above 32 weeks gestational age, BPD was considered if the baby was dependent on oxygen for 28 consecutive days [14
]. Oxygen was used to maintain saturations given by pulse oximetry in the range of 88 to 94% for RDS and 90 to 95% for BPD. Exogenous surfactant was administered through the endotracheal tube in babies on invasive mechanical ventilation or by INSURE in babies off invasive mechanical ventilation [15
Routine mechanical ventilation modes were patient-triggered modalities using a Babylog 8000+ (Drager, Lubeck, Germany
), SIPPV (synchronized intermittent positive pressure ventilation) until 2000, and SIPPV + VG (volume guarantee) or PSV + VG (pressure support ventilation + volume guarantee) after 2000 [16
]. High frequency oscillatory ventilation, at our unit, is used as a rescue ventilation using the Sensor Medics 3100 A (Sensor Medics Corporation, Yorba, Linda, CA, USA). Not intubated patients were placed on InfantFlow
nasal CPAP (Care Fusion, Yorba Linda, USA) with nasal prongs or mask with a pressure of 5–7
O, in prone position and started on caffeine, kept until 34 weeks of gestational age. Starting total fluid intake was 70
mL/kg/day and increased daily according to the hemodynamic status. Nasal CPAP (InfantFlow
) was used with pressures of 5-6
O in most cases but could be increased up to 7-8 in particular cases. Patients with apnoeas requiring stimulation were changed to NCPAP with synchronized pressure assistance (Infant Flow SiPAP, Viasys Health Care, Palm Spring, USA). Patients requiring FiO2
> 0.40 with respiratory distress and/or arterial PCO2
mmHg and pH < 7.20 were intubated for exogenous surfactant administration (poractant alfa). INSURE was routinely performed after an intravenous bolus of morphine (0.1
mg/kg). Naloxone (0.1
mg/kg, IV push) was used if needed, to reverse respiratory depression caused by morphine.
As early NCPAP and INSURE were introduced in our NICU in 2005, we compared demographic and clinical characteristics between two epochs (1997–2004 and 2005–2011, before and after their introduction, resp.). We, also, compared demographic and clinical characteristics between surviving preterm with and without BPD.
Histological chorioamnionitis was defined according to the Blanc classification [17
]: stage I, intervillositis; stage II, chorionitis; stage III, chorioamnionitis; funisitis, polymorphonuclear leukocytes in the Wharton's jelly or umbilical vessel walls; vasculitis-polymorphonuclear leukocytes in chorionic or umbilical blood vessel walls. All stages of chorioamnionitis were considered together. Proven neonatal sepsis was defined as any systemic bacterial or fungal infection documented by a positive blood culture. The criteria of Bell were used for the diagnosis and staging of necrotizing enterocolitis [18
]. Staging of retinopathy of prematurity was done according to the International Classification [19
]. Intraventricular haemorrhage was classified according to Papile et al. [21
]. Periventricular leukomalacia was classified according to de Vries and Rennie [22
]. Hemodynamically significant patent ductus arteriosus was diagnosed on the basis of the echocardiographic findings. The first evaluation is usually between 24 and 72 hours of life, with daily evaluation until closure of the ductus. The standard treatment is indomethacin.
The study protocol has been approved by our institute's committee on human research.
Continuous variables with symmetric distribution were characterized by mean (± standard deviation), those with asymmetric distribution by median (minimum–maximum values) and categorical variables were characterized by its absolute and relative frequencies. Mann-Whitney U test was used to compare two independent samples (asymmetric continuous variables) and chi-squared test or Fisher's exact test to compare categorical variables, the latest one for contingency tables 2 × 2 when expected values were less than 5. A multivariate analysis by logistic regression was performed to evaluate the outcome BPD. The results are presented by odds ratio (OR), 95% confidence interval (CI), and P value. The statistical analysis was performed using SPSS program v.19 (IBM, New York, USA) and a P value <0.05 was considered significant.