Risk factors for bronchopulmonary dysplasia among preterm infants born before thirty-two weeks of gestation in Palestinian private hospitals

Abstract

BACKGROUND

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease among premature infants, with long-term consequences for respiratory health, neurodevelopment, and overall growth.

AIM

To identify the major risk factors for BPD among preterm infants born before thirty-two weeks of gestation in private hospitals in the North West Bank, Palestine.

METHODS

A quantitative, retrospective cohort study was conducted in tertiary private hospitals equipped with neonatal intensive care units in the North West Bank. The study population included all premature infants born at < 32 weeks gestation, with a total sample size of 119 cases. Data were collected using a structured, self-developed tool comprising five sections: Demographic data, maternal history, birth and neonatal history, respiratory support and interventions, and infection/complications. Statistical analysis was performed using SPSS version 26, applying descriptive statistics, means, n (%) and inferential statistics, including the χ² test, to examine associations between maternal, neonatal, and clinical variables and the occurrence of BPD.

RESULTS

The mean birth weight of the infants was 1257.45 g. Most infants (88.2%) were born between 28-32 weeks of gestation, and 65.5% were male. Significant associations were found between BPD and maternal preeclampsia (P = 0.045) as well as patent ductus arteriosus (PDA). Common maternal conditions included preeclampsia (44.5%) and eclampsia (47.9%), while prevalent neonatal complications included PDA (58.5%), retinopathy of prematurity (31%), and sepsis (60.5%). All infants received mechanical ventilation (MV) and were administered surfactant. Notably, 75.6% required immediate intubation, reflecting severe respiratory distress.

CONCLUSION

This study identified low birth weight, gestational age, prolonged MV, and oxygen exposure as significant risk factors for BPD. Additional contributors included sepsis and intrauterine growth restriction. The findings underscore the importance of early detection, optimized respiratory management, and improved prenatal and neonatal care strategies to reduce the incidence and severity of BPD in preterm infants.

Key Words: Bronchopulmonary dysplasia; Preterm infants; Risk factors; Neonatal intensive care unit; Mechanical ventilation; Oxygen therapy

Core Tip: This retrospective study highlights key clinical determinants of bronchopulmonary dysplasia (BPD) in very preterm infants born before thirty-two weeks of gestation in Palestinian private hospitals. Low birth weight, younger gestational age, prolonged mechanical ventilation, and extended oxygen exposure were identified as the strongest predictors of BPD. Sepsis was also a significant contributing factor. Early identification of high-risk infants and optimization of respiratory support strategies may reduce the burden of BPD and improve outcomes in this vulnerable population.

INTRODUCTION

Many premature infants suffer from a persistent lung disease known as bronchopulmonary dysplasia (BPD), which primarily affects preterm neonates who require prolonged respiratory support during the early postnatal period[1]. BPD is characterized by arrested lung development, impaired alveolarization, and abnormal pulmonary vascular growth, resulting from a combination of prenatal and postnatal factors such as prematurity, inflammation, oxidative stress, mechanical ventilation (MV), and prolonged exposure to supplemental oxygen[2]. These pathological processes lead to chronic respiratory insufficiency and increased vulnerability to long-term pulmonary and neurodevelopmental complications[3].

Although Northway initially described BPD in 1967 as a consequence of ventilator-induced lung injury in preterm infants, the understanding and definition of the disease have evolved over time[1]. With advances in neonatal care and improved survival of extremely premature infants, contemporary BPD reflects disrupted lung development rather than solely postnatal lung injury. The current definition of BPD emphasizes disease chronicity and the need for supplemental oxygen for at least 28 days. Based on oxygen requirements at 36 weeks corrected gestational age, infants born at less than 32 weeks of gestation are classified as having mild BPD (no oxygen requirement), moderate BPD (21%-30% oxygen), or severe BPD (greater than 30% oxygen and/or positive pressure respiratory support)[2].

The prevalence of BPD, which varies from 11% to 50% and varies significantly by region, influenced by various diagnostic and therapeutic approaches. The risk of BPD increases with declining gestational age and birth weight, and it affects about 30% of infants born extremely low. The frequency of BPD in premature infants born before 32 weeks ranges from 12.9% to 41%, with rates as high as 80% in very premature infants, following a research by Ramos-Navarro et al[4].

Survival rates among premature infants have increased markedly due to advances in perinatal and neonatal care, including the use of exogenous surfactant therapy and prenatal corticosteroids[3]. Despite a reduction in complications such as neonatal respiratory distress syndrome (NRDS), necrotizing enterocolitis (NEC), and intraventricular hemorrhage, BPD remains a common and increasingly prevalent condition among premature infant[4]. This trend may be related to the improved survival of infants born at extremely early gestational ages[5].

The management of severe BPD is particularly challenging, as it is associated with an increased risk of mortality, prolonged hospitalization, and long-term dependence on respiratory support. Approximately 50% of premature infants with severe BPD who survive require hospital readmission within the first year of life, and nearly 25% die. In addition, these infants are two to three times more likely to experience neurodevelopmental impairments compared with term infants[3].

Recent clinical prediction models have identified several risk factors associated with the development of BPD, including lower gestational age, low birth weight, male sex, intrauterine growth restriction (IUGR), chorioamnionitis, maternal smoking, and race[6]. Postnatal factors such as pulmonary inflammation, patent ductus arteriosus (PDA), NRDS, and the need for invasive MV further increase the risk of BPD[3].

Among these, preterm birth and low birth weight are the most common risk factors present during both the prenatal and postnatal periods[7,8]. Premature infants weighing less than 1500 g are particularly vulnerable and often require prolonged MV and supplemental oxygen therapy[7]. In addition, these infants are more likely to develop respiratory distress syndrome, resulting in a greater need for oxygen and ventilatory support compared with full-term infants. Other important risk factors include male sex, IUGR, chorioamnionitis, maternal smoking during pregnancy, infections, and racial or ethnic disparities among parents[6].

The specific mechanisms by which these factors influence the severity of BPD remain poorly understood. However, identifying these risk factors may facilitate early detection and timely intervention, thereby helping to prevent the development of moderate or severe BPD[9].

This chronic lung disease is associated with significant long-term health complications, increased mortality, and higher healthcare costs[10,11]. Although numerous studies have identified various risk factors for BPD, data specific to the Palestinian population remain limited. Therefore, this study addresses an important healthcare gap by focusing on premature infants born before 32 weeks of gestation in Palestinian private hospitals. The findings aim to provide a comprehensive understanding of how selected maternal, neonatal, and prenatal factors influence the development of BPD in this population. The primary objective of the present study is to identify risk factors associated with BPD among premature infants born at less than 32 weeks of gestation in Palestinian private hospitals in the North West Bank.

MATERIALS AND METHODS

Study design

A quantitative, retrospective study design was employed to examine risk factors for BPD among premature infants born at less than 32 weeks of gestation in Palestinian private hospitals in the North West Bank.

Study site and setting

The study was conducted at a tertiary care private hospital in the northern West Bank that includes a neonatal intensive care unit (NICU) and utilizes a fully computerized health information system. This system contains comprehensive records of patients’ clinical data, treatments, and procedures, including detailed documentation by all healthcare providers involved in patient care.

Study duration

The study was conducted from January 2024 through December 2024.

Study population

The study population comprised premature infants born at less than 32 weeks of gestation who were admitted to NICUs in private tertiary hospitals located in the North West Bank, Palestine. The population included infants delivered and treated within this geographical region during the study period, ensuring representation of premature neonates receiving specialized neonatal care in the private healthcare sector of the North West Bank.

Sample

The sample was drawn from a tertiary care hospital in the North West Bank and included data extracted from the hospital’s database for the year 2024. A total population sampling method was applied, whereby all eligible cases during the study period were included. The study period extended from January 2024 through December 2024.

Inclusion criteria: Inclusion criteria were premature infants born at less than 32 weeks of gestational age, with a birth weight of ≤ 1500 g, and with complete medical records available.

Exclusion criteria: Infants with IUGR, major congenital malformations, or those receiving palliative care were excluded to reduce confounding effects on respiratory outcomes. Other neonatal conditions commonly associated with prematurity were not excluded and were considered relevant clinical variables in the analysis.

Sample size: Based on an alpha level of 0.05, a statistical power of 0.80, and a medium effect size of 0.3, the estimated minimum sample size calculated using G*Power was 88. A total population sampling method was applied, including all available premature infants with gestational age < 32 weeks who met the predefined inclusion criteria, resulting in a final sample of 119 infants.

Study instrument

The data collection tool was self-developed based on an extensive review of the literature addressing established maternal, neonatal, and clinical risk factors associated with BPD, including gestational age, birth weight, respiratory support, oxygen exposure, infection, and neonatal complications[2-4,9,12]. The instrument was reviewed and validated by a pediatric specialist and the research supervisor (PhD), and all suggested modifications were incorporated.

The survey consisted of five sections: Section one included demographic data (5 items); Section two covered maternal history (7 items); Section three addressed birth and neonatal history (4 items); Section four focused on respiratory support and interventions (8 items); and Section five included infection and complication variables (3 items).

Validity and reliability

The study demonstrated adequate internal validity, as the research methodology and data collection procedures were designed to accurately assess the relationship between the dependent and independent variables. Potential sources of bias and confounding factors were carefully addressed and controlled to ensure the validity of the findings. The reliability of the study instrument was acceptable, with a Cronbach’s alpha coefficient of 0.72. Prior to full data collection, the tool was reviewed for clarity and completeness by a pediatric specialist, and minor wording adjustments were made; a formal pilot study was not conducted due to the retrospective nature of the study and reliance on medical records.

Data collection

Data collection commenced after obtaining ethical approval from the Arab American University-Palestine Institutional Review Board (No. R-2024/A/123/N) and authorization from the participating private hospital administrations. Following approval by the medical directors, who are responsible for patient records and data protection, medical files of premature infants with gestational age less than 32 weeks who were admitted to the NICU between January 2024 and December 2024 were reviewed. All infants who met the predefined inclusion criteria were included in the study, resulting in a total of 119 eligible medical records. Data were extracted using the prepared study instrument.

Statistical analysis

The collected data were organized, reviewed, coded, tabulated, and analyzed using descriptive statistics, including n (%). Statistical analysis was performed using the SPSS software, version 26. Measures of central tendency and inferential statistical tests were applied to examine the relationships between independent and dependent variables. The χ² test was used to assess the significance of associations between categorical variables.

RESULTS

Demographic characteristics of the sample

Table 1 summarizes the demographic characteristics of premature infants diagnosed with BPD. Of the 119 premature infants included in the study, the majority (88.2%) were born between 28 and 32 weeks of gestation, while 11.8% were born before 28 weeks. With respect to sex distribution, 65.5% of the infants were male and 34.5% were female.

Table 1 Demographic characteristics of the studied premature infants.

Variable	Category	n (%)	mean (SD)	Minimum	Maximum
Gestational age at birth	Less than 28 weeks	14 (11.8)
	Twenty-eight to thirty-two weeks	105 (88.2)
Sex	Female	41 (34.5)
	Male	78 (65.5)
Birth weight (g)			1257.45 (196.57)	500	1500
Apgar score	At 1 minute		5.87 (1.34)	4	8
Apgar score	At 5 minutes		8.18 (0.72)	7	9

The mean birth weight was 1257.45 ± 196.57 g, with values ranging from 500 g to 1500 g. The mean Apgar score at 1 minute was 5.87 ± 1.34 (range: 4-8), which increased to 8.18 ± 0.72 at 5 minutes (range: 7-9).

Maternal and neonatal history

Maternal history:Table 2 presents the maternal and neonatal clinical characteristics of the study population. Most mothers (73.9%) received prenatal care, while 26.1% did not. The majority (79.8%) had no documented infections, including chorioamnionitis or urinary tract infections, whereas 20.2% experienced at least one infection. Preeclampsia was reported in 44.5% of cases, and eclampsia was observed in 47.9%. Gestational diabetes mellitus was less common, affecting 16.8% of mothers.

Table 2 Maternal and neonatal history variables.

Domain	Variable	Response	n (%)
Maternal history	Prenatal care received	No	31 (26.1)
		Yes	88 (73.9)
	Maternal infection (chorioamnionitis or urinary tract infection)	No	95 (79.8)
		Yes	24 (20.2)
	Preeclampsia	No	66 (55.5)
		Yes	53 (44.5)
	Eclampsia	No	62 (52.1)
		Yes	57 (47.9)
	Gestational diabetes mellitus	No	99 (83.2)
		Yes	20 (16.8)
	Premature rupture of membranes	No	42 (35.3)
		Yes	77 (64.7)
	Antenatal corticosteroids received	No	58 (48.7)
		Yes	61 (51.3)
	Mode of delivery	Cesarean section	98 (82.4)
		Vaginal delivery	21 (17.6)
	Multiple gestation	No	34 (28.6)
		Yes	85 (71.4)
Birth and neonatal history	Evidence of fetal distress	No	14 (11.8)
		Yes	105 (88.2)
	Resuscitation required at birth	No	47 (39.5)
		Yes	72 (60.5)
	Immediate intubation after birth	No	29 (24.4)
		Yes	90 (75.6)
Respiratory support and interventions	Oxygen therapy required	Yes	119 (100.0)
	Mechanical ventilation required	Yes	119 (100.0)
	Duration of mechanical ventilation	Less than 4 weeks	100 (84.0)
		Four weeks or more	19 (16.0)
	Surfactant therapy received	Yes	119 (100.0)
	Extubation and weaning trial performed	No	26 (21.8)
		Yes	93 (78.2)
	Early caffeine administration	Yes	119 (100.0)
	Dexamethasone received	No	51 (42.9)
		Yes	68 (57.1)
Infections and complications	Sepsis	No	47 (39.5)
		Yes	72 (60.5)
	Pneumonia	No	104 (87.4)
		Yes	15 (12.6)
	Necrotizing enterocolitis	No	102 (85.7)
		Yes	17 (14.3)
	Early-onset sepsis	No	61 (51.3)
		Yes	58 (48.7)
	Late-onset sepsis	No	88 (73.9)
		Yes	31 (26.1)
	Patent ductus arteriosus	No	49 (41.5)
		Yes	69 (58.5)
	Retinopathy of prematurity	No	82 (68.9)
		Yes	37 (31.1)

Premature rupture of membranes (PROM) occurred in 64.7% of pregnancies. Antenatal corticosteroids were administered to 51.3% of mothers prior to delivery, while 48.7% did not receive corticosteroids. Cesarean section (CS) was the predominant mode of delivery (82.4%), compared with vaginal delivery (17.6%). Multiple gestations accounted for 71.4% of pregnancies, whereas 28.6% were singleton pregnancies.

Birth and neonatal history:Table 2 summarizes the birth and neonatal history of the study population. Evidence of fetal distress was documented in the majority of cases (88.2%), while 11.8% showed no signs of distress. At birth, 60.5% of infants required resuscitation, whereas 39.5% did not. In addition, immediate intubation was required for 75.6% of infants, while 24.4% did not require intubation.

Respiratory support and intervention

Table 2 presents data on respiratory support and related interventions among the study population. All infants (100%) required supplemental oxygen therapy, underscoring the significant respiratory morbidity among premature neonates. MV was required for all infants. The majority (84.0%) received MV for less than four weeks, whereas 16.0% required ventilation for a longer duration.

Extubation and weaning trials were attempted in 78.2% of cases, while 21.8% remained dependent on respiratory support. Early caffeine administration was not documented in any case. Regarding postnatal steroid therapy, 57.1% of infants received dexamethasone, whereas 42.9% did not.

Infections and complications

Table 2 summarizes the infectious complications and comorbidities observed among the study population. Sepsis was a major concern, affecting 60.5% of infants. Pneumonia was diagnosed in 12.6% of cases, while NEC occurred in 14.3%. Early-onset sepsis was identified in 48.7% of infants, whereas late-onset sepsis was less frequent, occurring in 26.1%.

PDA was diagnosed in 58.5% of infants, underscoring its high prevalence among premature neonates. Retinopathy of prematurity (ROP) was reported in approximately 31% of cases; minor discrepancies in counts were attributable to repeated documentation in medical records.

Association between maternal history and neonatal complications variables associated with premature infants with BPD

χ² analyses were conducted to assess associations between maternal characteristics and neonatal complications among premature infants with BPD. A P value < 0.05 was considered statistically significant. Table 3 presents only those maternal–neonatal variable pairs that demonstrated statistically significant associations.

Table 3 Association between maternal characteristics and neonatal complications among preterm infants with bronchopulmonary dysplasia (χ² analysis), n (%).

Maternal variable	Exposure status	Neonatal outcome	Outcome present	Outcome absent	P value
Preeclampsia	No	Patent ductus arteriosus	30 (48.4)	32 (51.6)	0.045
	Yes		42 (73.7)	15 (26.3)
Eclampsia	No	Sepsis	33 (53.2)	29 (46.8)	0.046
	Yes		39 (68.4)	18 (31.6)
Eclampsia	No	Late-onset sepsis	10 (16.1)	52 (83.9)	0.009
	Yes		21 (36.8)	36 (63.2)
Premature rupture of membranes	No	Retinopathy of prematurity	8 (19.0)	34 (81.0)	0.020
	Yes		30 (39.0)	47 (61.0)
Multiple gestation	No	Late-onset sepsis	5 (14.7)	29 (85.3)	0.042
	Yes		26 (30.6)	59 (69.4)
Multiple gestation	No	Retinopathy of prematurity	5 (14.7)	29 (85.3)	0.008
	Yes		33 (38.8)	52 (61.2)

Percentages are calculated based on the total number of infants within each maternal exposure group. P values were calculated using the χ² test.

A significant association was observed between maternal preeclampsia and PDA (P = 0.045), with PDA diagnosed in 73.7% of infants born to mothers with preeclampsia. Maternal eclampsia was significantly associated with both neonatal sepsis (P = 0.046) and late-onset sepsis (P = 0.009); among infants of mothers with eclampsia, 68.4% developed sepsis and 36.8% developed late-onset sepsis.

Additionally, a history of PROM was significantly associated with ROP (P = 0.020), with ROP occurring in 39.0% of affected infants. Multiple gestations were significantly associated with both late-onset sepsis (P = 0.042) and ROP (P = 0.008), affecting 30.6% and 38.8% of infants from multiple births, respectively.

DISCUSSION

In the present study, the majority of infants diagnosed with BPD were born between 28 and 32 weeks of gestation. This finding is consistent with previous studies by Huang et al[1] and Valenzuela-Stutman et al[7], and supports global epidemiological evidence indicating that the risk of BPD increases with decreasing gestational age.

Additionally, most affected infants were male, a finding that aligns with reports by Cokyaman and Kavuncuoglu[5], Sucasas Alonso et al[3], and Kardum et al[13]. These studies suggest that male preterm neonates may be more susceptible to BPD due to sex-related genetic and hormonal differences that influence lung development.

Previous studies by Ding et al[12] and Huang et al[14] reported that approximately 26.1% of mothers did not receive adequate prenatal care, which represents an important risk factor for neonatal complications, including BPD. Insufficient prenatal care increases the likelihood of adverse conditions such as IUGR, which predisposes infants to impaired lung development and subsequent BPD.

In the current study, maternal hypertensive disorders, including preeclampsia and eclampsia, were significantly associated with the occurrence of PDA in premature infants. This finding is consistent with studies by Geetha et al[9] and Ding et al[12], which demonstrated that maternal hypertension-related complications may increase the risk of BPD through mechanisms such as prolonged intrauterine hypoxia and placental insufficiency, ultimately leading to impaired pulmonary development in newborns.

In the present study, the majority of infants’ mothers experienced PROM, a well-recognized risk factor for preterm birth and adverse neonatal outcomes. This finding is consistent with studies by Geetha et al[9], Bhunwal et al[15] and Lapcharoensap et al[16], which emphasized the association between PROM and BPD. Prolonged rupture of membranes increases the risk of intrauterine infection, leading to systemic inflammation in the neonate and subsequent lung injury.

A high proportion of infants in this study were delivered by CS. This finding aligns with reports by Rutkowska et al[17] and Mahmoud et al[18], who noted that increased CS rates are often associated with fetal distress or maternal complications, both of which may contribute to an elevated risk of BPD.

Fetal distress was observed in nearly all cases, and 60.5% of infants required resuscitation at birth. These results are consistent with findings by Ding et al[12], Kim et al[19], and Nakashima et al[20], which demonstrated that neonates exposed to perinatal hypoxia are more likely to require prolonged oxygen therapy and MV, both of which play a significant role in the development of BPD.

All premature infants in the current study required supplemental oxygen therapy; however, only a subset required prolonged MV (84% for less than four weeks and 16% for more than four weeks). According to Jensen et al[21], prolonged oxygen exposure and ventilatory support are major contributors to the pathogenesis of BPD, supporting the findings observed in this cohort.

In the current study, approximately two thirds of premature infants were diagnosed with neonatal sepsis, with nearly half presenting with early-onset sepsis and 26.1% developing late-onset sepsis. This finding is consistent with the study by Geetha et al[9], which demonstrated that sepsis exacerbates BPD by triggering a systemic inflammatory response that damages the immature lung and impairs alveolar development.

In addition, 58.5% of infants in the present study were diagnosed with PDA, supporting previous findings by Huang et al[1] and Yang et al[2], who reported a strong association between PDA and BPD. Increased pulmonary blood flow and fluid overload associated with PDA contribute to pulmonary injury and inflammation, thereby increasing the risk of BPD.

Furthermore, the results of the χ² analysis revealed a statistically significant association between maternal preeclampsia and the occurrence of PDA in premature infants. Infants born to mothers with preeclampsia were more likely to develop PDA compared with those born to normotensive mothers. This finding is consistent with Yang et al[2], who identified PDA as an independent risk factor for severe BPD.

A statistically significant association was observed between maternal eclampsia and the incidence of neonatal sepsis. Similar to the findings reported by Sucasas Alonso et al[3], infants born to mothers with eclampsia were more likely to develop sepsis compared with those born to mothers without eclampsia.

In addition, a strong association was identified between maternal eclampsia and late-onset neonatal sepsis. Infants whose mothers had eclampsia exhibited a significantly higher incidence of late-onset sepsis than those born to mothers without eclampsia. This finding is consistent with previous studies by Sharma et al[6] and Kardum et al[13].

Furthermore, a significant association was found between a maternal history of PROM and the development of ROP in neonates. In line with the findings of Geetha et al[9] and Lapcharoensap et al[16], infants born to mothers with PROM had a higher likelihood of developing ROP compared with those born to mothers without PROM.

The χ² test revealed a statistically significant association between multiple births and late-onset sepsis. Newborns from multiple gestations exhibited a higher incidence of late-onset sepsis compared with infants from singleton pregnancies. This association may be explained by the increased vulnerability of infants from multiple pregnancies, who are more likely to be born at lower gestational ages and with lower birth weights-both well-established risk factors for neonatal infection[6,9,13]. In addition, multiple-birth infants often require prolonged hospitalization, extended respiratory support, and exposure to invasive procedures, such as central venous catheterization, which increase the risk of nosocomial infections and late-onset sepsis[3,12,16]. These findings are consistent with previous reports, including the Croatian cohort described by Kardum et al[13], which identified multiple gestation as a significant contributor to late-onset sepsis among very preterm infants.

CONCLUSION

The findings of this study indicate that low birth weight, lower gestational age, prolonged MV, and exposure to supplemental oxygen are among the most significant risk factors associated with the development of BPD. These results are consistent with previous research and underscore the importance of early identification of high-risk infants and the implementation of targeted preventive strategies within NICU.

Furthermore, the study highlights the critical role of respiratory support in the pathogenesis of BPD, with prolonged invasive MV identified as a major contributing factor. The observed association between elevated oxygen exposure and lung injury reinforces the detrimental effects of oxidative stress on the immature developing lung.

Overall, this research enhances current understanding of BPD by providing a comprehensive analysis of both prenatal and postnatal risk factors influencing disease development. The consistency of these findings with existing literature strengthens their validity and contributes to the growing body of evidence guiding neonatal care. By identifying key contributors to BPD, this study supports efforts to optimize clinical practices and improve long-term health outcomes for preterm infants.