European Journal of Cardiovascular Medicine

Bronchopulmonary dysplasia (BPD) is the most common morbidity of surviving preterm infants and is associated with adverse long-term pulmonary and neurodevelopmental outcomes.¹ With advances in perinatal care increasing the survival of extremely preterm infants, the incidence of BPD has either remained static or risen in the last 20 years.²

BPD primarily occurs in extremely premature infants (23– 28 weeks of gestation) born during the late canalicular / early saccular stage of lung development.³ The lack of uniformity in the diagnostic criteria for BPD partly explains the wide variation in the reported incidence among different centers. Incidence of BPD ranged from 6% to 57%, depending on the definition chosen, and that studies that investigated correlations with long-term pulmonary and, or, neurosensory outcomes reported moderate to low predictive values regardless of the BPD criteria.^4,5

BPD has a multifactorial etiology; the major risk factors include prematurity, oxygen therapy, mechanical ventilation, infection, patent ductus arteriosus (PDA), anemia of prematurity and genetic predisposition. ^6,7 There are data from western country regarding incidence of BPD but very few data from India. Present study was aimed to Study of Bronchopulmonary dysplasia (BPD) in preterm neonates

Present study was single-center, retrospective study, conducted in department of Neonatology, at tertiary care hospital, India. Study duration was of 2 years (January 2016 to December 2016). Study was approved by institutional ethical committee.

Inclusion Criteria: All newborn babies admitted in our hospital of <34 weeks & <1.5 kg either vaginally or by caesarean section.

Retrospectively data was collected of babies less than 34 weeks and less than 1.5 kg. In this study definition used to diagnose Bronchopulmonary dysplasia was NICHD workshop definition. Mild BPD was defined as the need for supplemental oxygen at or beyond 28 days but not at 36 weeks' PMA; moderate BPD was defined as the need for supplemental oxygen at 28 days, in addition to supplemental oxygen at FiO₂ at or below 0.30 at 36 weeks' PMA; and severe BPD was defined as the need for supplemental oxygen at 28 days and, at 36 weeks' PMA, the need for mechanical ventilation and/or FiO₂ above 0.30.

Babies were studied retrospectively and various parameters were recorded to find out risk factors. Data regarding maternal factors viz antenatal steroid, Doppler abnormality, maternal infection was collected from maternal records. At day of life 3,7,14,28 and 36 weeks respiratory support either oxygen or CPAP or mechanical ventilation was evaluated to identify BPD.

These prenatal, perinatal and postnatal data collected for each baby were recorded into standardized data collection sheet for the purpose of this study. Data was collected and compiled using Microsoft Excel, analysed using SPSS 23.0 version. Frequency, percentage, means and standard deviations (SD) was calculated for the continuous variables, while ratios and proportions were calculated for the categorical variables. Difference of proportions between qualitative variables were tested using chi- square test or Fisher exact test as applicable. P value less than 0.5 was considered as statistically significant.

A total of 370 neonates were included in the study. Mean birth weight was 1064.04 ± 255.728 grams, mean gestational age was 30.197 ± 2.48 weeks & Male: Female ratio was 1.11:1. 60 neonates had BPD. BPD was classified as mild ,moderate and severe according NICHD definition. The incidence of BPD was found as 16.2%.

Table 1: General characteristics

We noted that birth weight, gestational age & SGA/AGA status were significantly associated to the severity of BPD. Severity of BPD did have predilection for particular gender.

There was statistically significant association of lower birth weight with increased severity of BPD. There was statistically significant association of lower gestational age with increased severity of BPD. We found that severe BPD have more predilection for SGA than AGA.

Table 2: Distribution of BPD cases according to birth characteristics

In our study, p value of 0.989 was obtained thus implying no significant association of Antenatal steroids received with severity of BPD. P value of <0.001 was obtained thus implying significant association of neonates receiving delivery room CPAP with severity of BPD.

P value of <0.001 was obtained thus implying significant association of surfactant received neonates with severity of BPD.

P value for this analysis was 0.0438bwhich reflects significant association Of PDA with increased severity and incidence of BPD

P value of <0.001 was obtained implying a significant association of postnatal sepsis with severity of BPD

P value of 0.001 reflects significant association of presence of mechanical ventilation with increased severity and incidence of BPD.

P value for this analysis was <0.001 which reflects significant association of ROP with increasing severity and incidence of BPD.

Deranged umbilical artery Doppler, Necrotising enterocolitis, Intraventricular hemorrhage were assessed as a possible risk factor in severity of BPD, but no significant association was noticed.

Table 3: Distribution Of BPD Cases Based On risk factors

BPD is the most common form of chronic lung disease in infancy. Premature birth alters lung growth and development and may predispose to pulmonary functional limitations and early chronic obstructive pulmonary disease. Many advances in neonatology in the last several decades have allowed for the resuscitation, support, and survival of more preterm infants. Although mortality associated with respiratory disease has been altered significantly by the use of antenatal corticosteroids, postnatal surfactant, improved respiratory support technology, and enhanced nutritional strategies, but the risk of developing long-term respiratory morbidity remains very high.

BPD continues to be one of the most common complications of premature infants. This disease presents several challenges to clinicians, and its effects can be seen not only in the lungs of these infants but also in many other organ systems. Most of the literature available on its incidence, associated risk factors, preventive and therapeutic strategies is from developed nations. There is a lack of information on these in literature available from Indian subcontinent. The present study is in attempt to analyse the incidence and associated risk factors for BPD.

Lack of uniformity in the diagnostic criteria for BPD explains the wide variation in the reported incidence. BPD has shown an incidence ranging from 6% to 57%, depending on the definition chosen. A study from PGI Chandigarh,⁸ the incidence of CLD was 50%, 8.1% and 2.3% among the babies with birth weight <1000 grams, 1000-1249 grams and 1250-1499 grams respectively. In that study, CLD was significantly associated with lower gestation and birth weight; lesser use of antenatal steroids; presence of PDA, septicemia or pneumonia; and higher FiO2 and longer duration of ventilation. In this study, the incidence of BPD was 16.2%(60/370) in babies <1500 grams & <34 weeks using NICHD definition. The incidence of BPD was 25.8% and 4.5% among babies with birth weight 500-1000gms and 1001-1500 grams respectively.

In a study, Canadian Neonatal Network reported that 28.1% of surviving infants born less than 25 weeks gestation developed BPD compared with only 4% of infants born at 29 to 32 weeks gestation.⁹ Another study in Israel showed 50.1% of surviving infants born at 24 to 25 weeks gestation developed BPD compared with only 4.1% born between 30 and 32 weeks.¹⁰ In the same cohort, 29.3% of infants who were born with birth weights between 1000 g and 1500 g and over 70% of infants with birth weights less than 1000 g developed BPD.

In this present study, no significant association was found between babies receiving antenatal steroids and incidence and severity of BPD (p=0.98) A study by Gagliardi L et al.,¹¹ showed although antenatal steroids reduce risk factors for bronchopulmonary dysplasia (BPD) in preterm infants, their effect on BPD is conflicting. The study observed that the relationship between antenatal steroids and BPD is partly mediated through a reduction in the classical risk factors. In an observational study, Carlo et al.,¹² found no significant decrease in rates of BPD or the composite outcome of death or BPD in 7,808 ELBW infants born to mothers who received antenatal corticosteroids.

In a secondary analysis from the Caffeine for Apnea of Prematurity (CAP) trial, DeMauro et al.,¹³ found higher rates of BPD in infants who were intubated at birth compared with those who were stabilized with noninvasive continuous positive airway pressure (CPAP). A recent meta-analysis of four RCTs compared early use of CPAP to intubation and mechanical ventilation.¹⁴ BPD rates were only modestly reduced with early CPAP (32.4% vs. 34.0%), and the results failed to meet statistical significance (RR, 0.91; 95% CI, 0.82–1.01).¹⁴

However, a significant benefit with early CPAP was observed for the combined outcome of BPD, death, or both at 36 weeks PMA (RR, 0.91; 95%CI, 0.84–0.99).¹⁴ In our study, babies requiring early CPAP had increased incidence and severity of BPD. (Table 8, Figure 7).25.11%of babies requiring CPAP had BPD compared to 3.8% who did not require early CPAP. This correlation was statistically significant(p<0.001).

Since heart diseases can affect the oxygen saturation in the blood the possible association of congenital heart disease with BPD has been evaluated in various studies, especially with patent ductus arteriosus which is common lesion in preterm. There is strong evidence to support an association but not a causal relationship between persistent PDA and BPD by Rojas et al.,¹⁵ Benitz and Trzaski et al.¹⁶

A recent Cochrane Review found no difference in the incidence of BPD following medical versus surgical closure of PDA in preterm infants, although the analysis contained only a single small RCT.¹⁷ In a systematic review of all RCTs evaluating both surgical and pharmacologic methods of PDA closure, Benitz et al.¹⁶ found no reduction in BPD or the combined outcome of death or BPD with any therapy. In contrast to other studies our study showed a significant association between PDA and incidence and severity of BPD (p value is 0.048)

Multiple observational studies implicate postnatal sepsis as an independent risk factor for BPD.^10,11,12 Lahra et al.,¹⁸ reported a similar decrease in BPD with histologic chorioamnionitis alone but an increase when postnatal sepsis was also present. These findings suggest that postnatal infection may be a more important predictor of BPD than antenatal inflammation. Although the direct role infection plays is unknown, growing evidence suggests systemic inflammation coupled with changes in vascular permeability lead to immediate alveolar injury and possibly long-term disruption of alveolarization.¹⁸ In the present study we found a signification association between postnatal sepsis with incidence and severity of BPD. (p value <0.001)

In our study, no significant association was observed between NEC and BPD. A study showed necrotizing enterocolitis (Oh et al., 2005) was associated with BPD. Laughon et al. recently developed a predictive model using data from the NICHD NRN Benchmarking Trial.¹⁹ This model incorporates gestational age, birth weight, race and ethnicity, sex, respiratory support and fractional of inspired oxygen in a parsimonious model, providing estimates of severity of BPD or death by postnatal day. It was noteworthy that several previously described risk factors- PDA, NEC, sepsis and postnatal corticosteroids did not significantly improve the prediction of BPD after adjustment for the other six factors.

The overall incidence of BPD in the study was 16.21%. Out of various risk factors, the factors to be significantly associated with BPD were low birth weight, less gestational age, SGA, delivery room CPAP, surfactant, deranged umbilical artery Doppler, mechanical ventilation, postnatal sepsis, PDA and ROP. Gender, Antenatal steroids, IVH and NEC was not associated significantly associated with severe BPD.

Conflict of Interest: None to declare

Source of funding: Nil

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