Differences in Risk Factors and Predictors of Preterm Twin Infants with Bronchopulmonary Dysplasia: A retrospective study

doi:10.21203/rs.3.rs-3877127/v1

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Differences in Risk Factors and Predictors of Preterm Twin Infants with Bronchopulmonary Dysplasia: A retrospective study

https://doi.org/10.21203/rs.3.rs-3877127/v1

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Background

To evaluate the differences in clinical characteristics, BPD risk factors and predictors in preterm twin infants.

Methods

A retrospective, single-centre study was conducted on preterm twins admitted to the neonatal intensive care unit (NICU) of The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, from January 2021 to December 2022. Data, including perinatal and critical postpartum data, were collected for twin pairs with gestational age (GA) ≤ 31 weeks and birth weight ≤ 2500 g from clinical medical records, including perinatal data and critical postpartum information. Chi-square or nonparametric tests and multiple logistic regression models were used to analyse significant clinical parameters and characteristics for BPD between the two groups and to compare risk factors, respectively.

Results

A total of 233 twin infants were included in this study. Among them, 183 pairs had BPD, consisting of 366 twin infants. Among twins with BPD, 184 (50.3%) were discordant, and 182 (49.7%) were in one of the twin pairs with BPD. Extremely low birth weight infants (< 1000 g) and extremely preterm infants (GA < 28 weeks) were typical of twin pairs with both BPD (35.9% and 52.7%), while low birth weight infants (< 2500 g) and very preterm infants (GA > 28 < 31 weeks) were more common in one of the twin pairs with BPD (35 .2% and 86.8%). Preterm infants with a length/height between 25 cm and 35 cm were typically twin pairs with BPD (79.7% vs 20.3%). Among the twin pairs with both BPDs, 94 (51.1%) had a head circumference of 22–26 cm compared with 34 (18.7%). Among the risk factors, asphyxia, PDA, RDS, pulmonary hypertension, ROP, IVH, bloodstream infections, hypothyroidism, and hypoproteinaemia were more prevalent in both pairs of twins with BPD. Among the interventions, HFV, IMV, BiPAP, oxygen therapy, and HFNC therapy had significantly different effects on the two groups. The duration of these interventions also significantly differed between the two groups.

Conclusions

These data demonstrated that risk factors and predictors of BPD in preterm twins vary in magnitude and severity, particularly in extremely low birth weight infants, extremely preterm infants with smaller head circumferences, and infants with short length/height. The need for mechanical ventilation, duration of ventilation, and medication use increased in pairs of twins with both BPD. Thus, this study adds to the existing knowledge on the early detection of risk factors and stratification of clinical management strategies for preterm twins at the individual level.

Health sciences/Health care

Health sciences/Neurology

Health sciences/Risk factors

Bronchopulmonary dysplasia

twin pairs

preterm infants

mechanical ventilation

risk factors

Preterm birth represents a significant public health problem, causing more than 15 million live births each year (1). Preterm birth is the leading cause of neonatal mortality and morbidity, with infants born before 37 weeks of gestation being at increased risk of respiratory distress syndrome, bronchopulmonary dysplasia (BPD), and other complications (2, 3). Multiple pregnancies, especially twin pregnancies, are particularly vulnerable to developing BPD due to their increased susceptibility to various risk factors (4, 5). Despite advances in neonatal care, BPD incidence has not decreased. The definition of BPD has changed over time to better understand its pathophysiological mechanisms. BPD occurs from the prenatal to postnatal period after birth and persists after discharge from the neonatal intensive care unit. It is characterised by impaired alveolar and vascular development, inflammation and pulmonary fibrosis, leading to reduced lung function and respiratory distress (6). Reduced alveolar development is also evident, which may be due to impaired angiogenesis and alveolar formation in preterm infants born in the early stages of lung development (6, 7).

The incidence of BPD varies depending on the definition and diagnostic criteria used, as well as the population studied. In general, infants born before 32 weeks of gestation and those with a birth weight of less than 1500 grams are at highest risk of developing BPD, with an incidence of 45% in infants born at 29 weeks of gestation (8, 9). The incidence of BPD in premature twins is greater than that in singleton pregnancies, with some studies reporting rates of up to 50% (10, 11). Despite advances in neonatal care, the incidence of BPD has remained stable or even increased, particularly in extremely premature infants (12). A recent study has shown that the increased survival rate of extremely low gestational age neonates (ELGANs) has contributed to the increasing prevalence of BPD; approximately 35% of ELGANs develop BPD (13). According to a retrospective study by Smith et al. (14), the incidence of BPD is significantly greater in twins (29.9%) than in singletons (23.6%). Another study reported similar results (15). These findings highlight that twins face unique challenges related to foetal growth, the intrauterine environment, and delivery, which may increase the risk of BPD.

Identifying high-risk infants as early as possible during the clinical course is critical for targeted interventions and novel therapies. Premature birth is the leading risk factor for developing BPD; twins are at even greater risk than singletons are. Studies have shown that twins are more likely to develop FGR than singletons are, which may contribute to a greater risk of BPD (4, 16). In addition, twins are more likely to suffer from twin-to-twin transfusion syndrome (TTTS) or other hemodynamic imbalances in utero, which can also affect their lung development (17, 18). Other factors significantly associated with a higher risk of moderate to severe BPD include birth weight, male sex, high-frequency oscillatory ventilation, duration of invasive mechanical ventilation, inhaled nitric oxide, patent ductus arteriosus, and late-onset sepsis (19). Extreme prematurity, extremely low birth weight, and small for gestational age are primarily associated with more severe BPD (20).

Recent studies have identified various risk factors and predictors of BPD in preterm infants to help guide clinical management and appropriate intervention strategies. However, there is insufficient evidence to demonstrate the differences between twin pairs with BPD regarding these risk factors and predictors in preterm infants. Such information is needed to better understand and formulate appropriate management strategies. Therefore, this study aimed to identify and compare risk factors and predictors contributing to preterm twins with BPD and to examine the impact of the identified risk factors and predictors on healthcare providers and researchers in neonatal care. We hypothesised that BPD risk factors and predictors would be more prevalent in twin pairs with both BPD subtypes and that they would be more susceptible to BPD occurrence, severity, and associated comorbidities.

Study design and participants

This retrospective study included clinical data for preterm twin infants with a GA < 32 weeks admitted to the neonatal intensive care unit (NICU) of The Third Affiliated Hospital of Guangzhou Medical University. All consecutive live-born twin pairs born at The Third Affiliated Hospital of Guangzhou Medical University between 2021 and 2022 were eligible for inclusion. Preterm infants with a GA < 32 weeks postmenstrual age (PMA) and birth weight < 2500 g diagnosed with BPD were divided into two groups, i.e., twin pairs with BPD and one of the twin pairs with BPD. The exclusion criteria were singleton birth, missing or incomplete data sets, congenital malformations or syndromes with a potential impact on the respiratory system, death before fulfilling the BPD definition, the occurrence of TTTS, hydrops foetalis, GA > 32 weeks and hospital stay < 28 days.

Study factors

The following maternal and neonatal baseline characteristics were collected from medical records in accordance with relevant guidelines and provisions.

The sociodemographic variables and perinatal factors include sex, gestational age, birth weight, birth sequence, intrauterine asphyxia, amniotic fluid, length/height, head circumference, hospital stay, hospital discharge status, corrected age at discharge, maternal age, mode of conception, prenatal steroid use, gestational diabetes mellitus (GDM), diabetes mellitus, maternal height, maternal education, and thyroid dysfunction.

Complications: neonatal RDS, sepsis, anaemia, pulmonary haemorrhage, bloodstream infections (BSI), CNS infections, hypothyroidism, necrotising enterocolitis (NEC), pulmonary hypertension, persistent pulmonary hypertension of the newborn (PPHN), patent ductus arteriosus (PDA), hypoproteinaemia, retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), and periventricular leukomalacia (PVL).

Treatment: Pulmonary surfactant (PS), antibiotics, steroids, dexamethasone, hydrocortisone, and budesonide.

Interventions: invasive mechanical ventilation (IMV), high-frequency ventilation (HFV), CPAP, BiPAP, oxygen therapy (OT), nasal tube oxygen (NTO), NIPPV, and high-flow nasal cannula (HFNC).

Ethics

This study was approved by the Institutional Review Board (IRB) of The Third Affiliated Hospital of Guangzhou Medical University, and the requirement for informed consent was waived. All procedures were conducted under the approved ethical guidelines and the Declaration of Helsinki.

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics Version 25.0 (SPSS, Inc., an IBM company, Chicago, IL, USA). The chi-square test or Fisher exact test was used to analyse categorical variables for within-pair differences. Continuous data with a normal distribution are presented as the mean and standard deviation and were analysed via one-way variance analysis. A multivariate regression model was used for statistically significant variables according to the binary analysis process. The final selected factors were used as hybrid factors to calculate the odds ratios ORs) and corresponding 95% confidence intervals (CIs). All p < 0.05 was considered to indicate statistical significance.

Patients characteristics

Two hundred and thirty-three twin pairs that delivered 24 weeks or older met the inclusion criteria; these included 466 infants. Of the 233 twin pairs, 50 were classified as having no BPD, and 183 pairs had BPD; these included 366 infants in total. There were 95 (52.2%) males and 87 (47.8%) females in one of the twin pairs with BPD and 107 (58.2%) males and 77 (41.8%) females among the twin pairs with both BPD. There were 38 (20.8%) infants born at 25–26 − 6/7 weeks for both twin pairs with BPD, 59 (32.1%) infants born at 27– 28 − 6/7 weeks for both twin pairs with BPD and 24 (13.2%) for one of the twin pairs with BPD, 83 (48.3%) vs 96 (52.7%) infants born at 29–30 − 6/7 weeks, and 4 (2.2%) vs 62 (34.1%) infants born at 30 weeks or older in each group, respectively. There were 97 (52.7%) that were extremely preterm (GA ≤ 28 weeks) in both twin pairs with BPD compared to 24 (13.2%) in one of the twin pairs with BPD, while 87 (47.3%) and 158 (86.8%) were very preterm infants (GA 28–31^+ 6 weeks), respectively. In twin pairs with both BPD, 7 (3.8%) infants had birth weight between 500–700 g compared to 1 (0.5%) in one of the twin pairs with BPD, 59 (32.1%) in infants with 700–1000 g vs 15 (8.2%) infants, and 77 (41.8%) in infants with 1000–1300 g vs 43 (23.6%), respectively. Comparable results were also observed for infants with BPD at different head circumferences and lengths/heights (table 1). There was a significant statistical difference between lighter infants and heavier infants in one of the twin pairs with BPD (41 [22.5%] and 141 [77.5%], respectively). However, there was no significant difference in the number of twin pairs with both BPD. Seventy-five (43.9%) infants had mild BPD; 52 (30.4%) had moderate BPD; and 44 (25.7%) had severe BPD in both twin pairs; and 18 (48.6%), 12 (32.4%) and 7 (18.9%) had BPD in one of the twin pairs, respectively. These results showed that infants with both BPD had a greater tendency to develop mild, moderate or severe BPD.

In terms of discharge status, 163 (88.6%) of the twin pairs with both BPD were discharged home, 11 (6.0%) were discharged to other hospitals, 6 (3.3%) were self-discharged, and 4 (2.2%) died; in contrast, 172 (94.5%), 2 (1.1%), 7 (3.8%) and 1 (0.5%) in one of the twin pairs, respectively. Among the twin pairs with both BPD, 73 (39.7%) were hospitalised for more than three months, 22 (12.1%) were hospitalized for one of the twin pairs with BPD, and 36 (19.6%) were hospitalised for more than four months in twin pairs with both BPD, while vs 6 (3.3%) were hospitalized for one of the twin pairs with BPD. In contrast, 138 (75.8%) in one of the twin pairs stayed in the hospital for two months, compared to 68 (37.0%) in twin pairs with both BPD. These data indicate that twin pairs with both BPD are more likely to stay in the hospital longer than their counterpart are. Gestational age at discharge and mode of conception were significantly different between the two groups. There were no differences in other characteristics, such as maternal age, maternal height, weight gained during pregnancy, maternal education, gestational diabetes, sex, birth sequence, or amniotic fluids. These characteristics are summarised in Table 1.

Effect of complications in twin pairs with BPD

To determine the effects of asphyxia, NRDS, pulmonary haemorrhage (PH), NEC, PDA, ROP, PVL, IVH, bloodstream infections (BSI), PPHN, NHT, hypoproteinaemia (HP), sepsis and anaemia on BPD, we assessed the associations of each of these complications with BPD and infant outcomes. There were no differences between these two groups in terms of the indices mentioned above, except for asphyxia, NRDS, PH, PDA, ROP, PVL, IHV, BSI, hypothyroidism (HT), and HP, as shown in table 2. One hundred and eighty-four (100%) preterm twin infants with both BPD had neonatal respiratory distress syndrome (NRDS), 91 (49.5%) had PDA, 136 (73.9%) had ROP, 21 (11.5%) infants had PVL, 15 (8.2%) had pulmonary hemorrhage, 79 (42.9%) had IVH, 115 (63.2%) had bloodstream infections (BSI), 34 (18.6%) had asphyxia, 42 (23.3%) had hypothyroidism, and 103 (56.6%) had hypoproteinaemia (HP), which was significantly different from the other group. The two groups were not significantly different in infants with BPD complicated by anaemia. However, anaemia severity was significantly different between infants with BPD and healthy controls. Severe anaemia was more common in twin pairs with both BPD (130/203, 71.4%) than in one of the twin pairs with BPD (73/203, 43.2%). In contrast, moderate anaemia was more common in one of the twin pairs with BPD than in twin pairs with both BPD (88/134, 52.1% vs 46/134, 25.3%, respectively). There were also a differences in maternal thyroid dysfunction and abnormal uterine and maternal diabetes mellitus between the two groups (Table 2).

Among the complications, multivariate logistic regression analysis revealed that PDA, ROP, IVH, BSI, PPHN, HT and HP were the most critical risk factors for preterm twin pairs with both BPD. The odds ratio for PDA was 4.478 (95% CI = 2.535–7.909, P < 0.000), ROP 2.118 ((95% CI = 1.216–3.690, P < 0.008), IVH 2.965 ((95% CI = 1.686–5.213, P < 0.000), BSI 2.547 ((95% CI = 1.506–4.307, p < 0.000), HT 3.680 ((95% CI = 1.646–8.229, p < 0.002) and HP 2.065 ((95% CI = 1.233–3.460, P < 0.006). Our statistical data demonstrated that PPHN (OR = 0.118; 95% CI = 0.021–0.677; p < 0.017) was related to an increase in the risk increase of BPD but was not as strong as other factors (Table 6).

Effect of treatment in twin pairs with BPD

To determine the clinical significance of the abovementioned patterns, we assessed the association of treatment interventions in twin pairs with BPD. Among the groups, there were statistically significant differences in antibiotic, pulmonary surfactant (PS), steroid and dexamethasone use, but not in hydrocortisone or budesonide use among preterm twin infants with BPD. Among the twin pairs with both BPD, 182 (98.9%) were given PS, 171 (94.5%) were given steroids, 182 (98.9%) were given antibiotics, 37 (21.1%) were given hydrocortisone, 131 (74.4%) were given dexamethasone, and 40 (22.9%) were given budesonide. In contrast, 170 (93.4%) in one of the twin pairs with BPD received PS, 31 (75.6%) received steroids, 157 (86.3%) received antibiotics, 7 (17.9%) received hydrocortisone, 22 (56.4%) received dexamethasone, and 12 (30.8%) received budesonide in one of the twin pairs with BPD (Table 3). Among the twin infants who were on PS, 96.7% (178/331) of the infants used artificial PS for both with BPD, and 84.1% (153/331) for only one of the twin pairs with BPD, 2.2% (4/21) and 9.3% (17/21) used calf PS in each group, respectively. There was no significant difference in the number of infants who received one or two PSs between the two groups: 162/322 (89.0%) and 160/322 (94.1%) for one PS, and 20/30 (11.0%) and 10/30 (5.9%) for two PSs. These data showed that preterm twin infants with both BPD received more PS and steroids than other infants did. Among the two groups, antibiotics were used mainly for treatment (289/339, 85.3%), whereas prophylaxis was used on 50/339 (14.7%). The route of PS administration did not significantly differ among the groups, nor did the duration of treatment (data not shown).

Effect of interventions in twin pairs with BPD

Six of the eight interventions (IMV, HFV, CPAP, NIPPV, BiPAP, oxygen therapy, NTO, HFNC) were associated with increased risks of BPD in both twin infants. These interventions also included large proportions of infants with BPD. Seventeen 17 (9.3%) of the 366 infants were on high-frequency ventilation (HFV) for both twin pairs with BPD, and one (0.5%) was on HFV for one of the twins with BPD; these differences were statistically significant (p < 0.000). One hundred and twenty-three infants (67.2%) out of 366 infants were on invasive mechanical ventilation (IMV) for both twin pairs with BPD, whereas 44 (24.2%) in one of the twins with BPD were on IMV. These two groups of patients were significantly different (p < 0.000). BiPAP (63/366, 34.4%), oxygen therapy (136/366, 73.9%) and high-flow nasal cannula (HFNC) therapy (98/53.6, 36.7%) were significantly different between the groups. Nasal tube oxygen (NTO), continuous positive airway pressure (CPAP) and noninvasive positive pressure ventilation (NIPPV) did not significantly differ (Table 3). The duration of these interventions was also different between the two groups (Table 4). Prolonged use of IMV and HFV was also associated with an increased risk of BPD, especially for twin pairs on IMV and HFV ventilation for more than two months. This difference was more pronounced for IMV, followed by HFNC, BiPAP, oxygen therapy (OT) and HFV. These data show that preterm twin infants with both BPD have longer durations of use of these interventions and, therefore, an increased risk of BPD development compared to one of the twin pairs with BPD.

Among the interventions, multivariate logistic regression analysis demonstrated that HFV, IMV, BiPAP and HFNC therapy were associated with increased BPD in preterm twin infants. The odds ratio for HFV was 7.983 (95% CI = 0.980-65.017, P < 0.052), IMV was 4.473 (95% CI = 2.754–7.264, P < 0.000), BiPAP was 2.241 (95% CI = 1.201–4.183, P < 0.011), and HFNC was 1.985 (95% CI = 1.194–3.301, P < 0.008). Surprisingly, oxygen therapy (OT) utilisation and duration were also associated with an increased risk of BPD in twin infants. The odds ratio for OT was 1.759 (95% CI = 1.065–2.905, p < 0.027) (Table 5). These data show that twin infants with both BPD are at greater risk of complications associated with these interventions, such as invasive mechanical ventilation, high-frequency ventilation and high-flow nasal cannula.

Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity and is characterised by chronic lung disease in premature infants. The definition and classification of bronchopulmonary dysplasia (BPD) currently used in clinical practice may not accurately predict long-term respiratory and neurological outcomes in preterm infants due to changes in the patient population and the introduction of new factors (13). The first comprehensive definition of the NICHD is based on oxygen requirements and age-related milestones at 28 days and 36 weeks postmenstrual age (PMA). However, different stakeholders have different interpretations of the diagnosis, and each definition has its limitations. Although not thoroughly validated, Jensen's classification is a more refined and straightforward approach. Institutions and databases are switching to the Jensen grading while awaiting further assessments (21). BPD poses a high risk to infants and represents an economic burden on healthcare providers and caregivers/parents (22).

Management of BPD in preterm twins involves a multifaceted approach that includes preventive measures, supportive care, and pharmacological interventions (23, 24). Preventive measures include prenatal care, early detection and treatment of maternal infections, and prevention of preterm birth (25). Supportive care includes respiratory support (26), nutritional support (27, 28), and surfactant therapy. Pharmacological interventions may include corticosteroids, bronchodilators, antioxidants and diuretics (7, 29), as well as home oxygen for infants weaned from ventilators (30, 31). Depending on disease severity, gestational age, and comorbidities, these interventions are tailored to the individual patient. Other treatment strategies, such as stem cells, are being investigated for the management of BPD and its associated comorbidities (32), as is the development of orphan drugs for BPD treatment (33). However, the variability in treatment strategies likely reflects the lack of evidence regarding the optimal treatment for infants with BPD.

The present study has demonstrated significant differences between twin infants with BPD in terms of sex, gestational age, weight (lighter vs heavier infants), birth weight, head circumference, length/height, Apar score, pulmonary surfactant, prenatal steroids, postnatal steroids, antibiotics, BPD severity, risk factors, mechanical ventilation strategies and duration on those ventilators, irrespective of chorionicity. Among preterm twin infants with both BPD, those with a gestational age (GA) between 25 and 28 weeks (extremely preterm infants) and a birth weight (BW) of between 500 and 1300 g (extremely low birth weight and very low birth weight) were at greater risk of developing BPD than were those in the other GA and BW groups. Similarly, a head circumference (HC) of 22–26 cm in height and a length/height between 25–35 cm were associated with an increased risk of BPD. These results showed that the younger gestational age and the lower the birth weight were, the greater the tendency for developing BPD in preterm twin infants, as was the trend for head circumference and length/height.

Recent studies have identified various risk factors associated with BPD in preterm infants (34–36). Accordingly, our study showed that twin pairs with both BPD have a greater risk of developing BPD aggravated by these complications, including asphyxia, pulmonary hemorrhage, NRDS, bloodstream infections (BSI), hypothyroidism, IVH, ROP, hypoproteinaemia, PPHN, pulmonary hypertension and PDA. Among these factors, PDA, ROP, IVH, BSI, hypothyroidism, hypoproteinaemia and PPHN were identified as the main risk factors associated with BPD in preterm twin pairs. The study also showed that mechanical ventilation characteristics, such as the frequency and duration of invasive mechanical ventilation (IMV), high-frequency ventilation (HFV), bilevel positive airway pressure (BiPAP), and incubator oxygen therapy (OT), were significantly greater in twin infants with both BPDs. Among these interventions, IMV, OT, BiPAP, and HFNC therapy were identified as risk factors associated with BPD in both sets of twins. Our results are consistent with those of previous studies (37, 38). The one-minute and five-minute Apgar scores differed between the two groups, suggesting that twin pairs with both BPD were more likely to suffer from mild or severe asphyxia during delivery. Therefore, one- and five-minute Apgar are risk factors for BPD in both twin pairs. A Korean study reported that a five-minute Apgar score is a risk factor for very low birth weight infants (39). Our study revealed that extremely low birth weight infants were typical of twin pairs with both BPD, while very low birth weight infants were typical in one of the twin pairs with BPD.

The evidence for the effectiveness of postnatal corticosteroids in reducing the incidence of BPD is limited and conflicting, and there is no consensus on their use and benefits in this population. Recent studies have shown that corticosteroids may not reduce BPD incidence due to increased survival, and a balanced approach is needed to reduce lung damage (40, 41). Another study recommended against systemic corticosteroid administration in preterm infants (42), the effect of systemic corticosteroid regimens on mortality, pulmonary morbidity or long-term neurodevelopment impairment outcomes is uncertain (43). Recent clinical trials have shown that administering hydrocortisone to ventilated preterm infants does not improve BPD incidence or death (44, 45), as hydrocortisone does not improve survival rates in preterm infants with BPD (46). The present study showed that dexamethasone, hydrocortisone and budesonide were administered more frequently in pairs of twins with both BPDs than in the other group. This finding implies that the use of steroids in both pairs of twins with BPD may confer a greater risk of developing BPD and other associated comorbidities. However, further research is needed to confirm this hypothesis. Our results further showed that prenatal steroid administration was more commonly used in twin pairs with both BPD than in the other group, but no difference in improvement in outcomes was noted between these twin pairs. A recent Cochrane review also revealed no significant difference in BPD incidence between the antenatal corticosteroids (ACS) group and placebo group (47). While ACS has shown benefits in terms of lung maturation and prevention of RDS, its effects on the incidence of BPD, particularly in multiple pregnant women, remain uncertain. Prenatal steroids are also currently not recommended for late preterm/early preterm infants (48).

Mechanical interventions are the mainstay for treating respiratory problems in preterm infants (49–51). However, recent studies have shown that mechanical ventilation and ventilator-induced lung injury (VILI) are critical risk factors for developing BPD (52). In addition, mechanical ventilation in preterm infants can lead to changes in white and grey matter in the brain, including altered myelination, neuronal loss, and thinning of the corpus callosum (40). Our present study showed that preterm twins with a GA < 28 weeks were more likely to receive invasive mechanical ventilation or high-frequency ventilation and required more days during these interventions. Infants with birth weights < 1300 g were more common among twin pairs with both BPD and the use and duration of mechanical ventilation. Therefore, these factors are strongly associated with BPD incidence and could simultaneously serve as predictors of BPD in twin pairs. Another study has reported similar risk factors and predictors of BPD in ventilated preterm infants (38).

Furthermore, our present study showed that twin pairs with both BPD had more frequent use of high-flow nasal cannula (HFNC) therapy and longer durations of HFNC therapy, which increased the risk of BPD. These results suggest that HFNC may negatively affect the number of ventilator days and postnatal steroid use and contribute to prolonged hospital stays of preterm twins. Another study reported that HFNC is associated with long-term adverse outcomes (53). Even the use of nasal high flow (nHF) is associated with increased treatment failure (54).

Recently, studies have shown that BPD adversely affects neurodevelopment outcomes in preterm infants, as indicated by a decreased head circumference, cerebral palsy, and decreased cognitive and language skills (7, 55). Our study showed that a smaller head circumference was more common in twin pairs with both BPD. Similar results were also observed for twin pairs with a length/height of less than 34 cm. This means that twin infants with both BPDs are at greater risk of developing neurodevelopmental sequelae. Therefore, healthcare professionals should be aware that preterm infants with BPD, especially twin pairs with both BPD, are at high risk for poor developmental outcomes throughout childhood. Identifying these risk factors for BPD and the differences between preterm twin infants may help clinicians assess the individual risk profiles of preterm infants.

This study has practical implications for clinical practice, as it allows health professionals to identify and classify high-risk preterm twins who may require closer monitoring, resource prioritisation, and targeted interventions based on risk level to prevent or treat BPD in twin pairs. This study also highlights the ongoing challenge of high rates of BPD despite advances in neonatal care and emphasises the need for continued research and interventions in this area. Future studies should also aim to determine the most appropriate corticosteroid treatment strategies for BPD, considering factors such as the timing of administration, the specific corticosteroid used, and the judicious use of mechanical intervention strategies in preterm twin infants. Furthermore, long-term follow-up studies are needed to assess the impact of BPD on neurodevelopmental outcomes and quality of life in affected infants.

This study has several limitations. First, the study was conducted in a single neonatal intensive care unit (NICU) at a specific hospital, which may limit the generalizability of the results to other settings. Second, the study relied on a retrospective analysis of clinical data, which may introduce potential biases and limitations in terms of data collection and accuracy. Third, the study did not examine other potential risk factors or variables that may contribute to differences in twin pairs with BPD. Finally, the study did not examine long-term outcomes or follow-up data for the infants, which could provide further insight into the impact of BPD severity on twin infants.

Preterm twins are more likely to develop BPD than singleton preterm infants are. This study highlights the importance of considering multiple risk factors and predictors in preterm twin infants with BPD. Understanding these factors may help in the implementation of preventive measures, early detection, and targeted interventions to reduce the incidence and severity of BPD in this vulnerable population. However, further research is needed to validate these findings and explore novel predictive markers and therapies to improve outcomes for preterm twin infants with BPD.

BPD: Bronchopulmonary dysplasia; IVF: In vitro fertilisation; RDS: Respiratory distress syndrome; PH: Pulmonary hemorrhage; NEC: Necrotizing enterocolitis; PDA: Patent ductus arteriosus; ROP: Retinopathy of prematurity; PVL: Periventricular leukomalacia; IVH: Intraventricular hemorrhage; BSI: Bloodstream infections; CNSI: Central nervous system infections; PPHN: Persistent pulmonary hypertension of the newborn; HT: Hypothyroidism; MTD: Maternal thyroid dysfunction; AU: Abnormal uterine; DM: Diabetes Mellitus; PS: Pulmonary surfactant; HCS: Hydrocortisone; DXM: Dexamethasone; BUD: Budesonide; HFV: High frequency ventilation; IMV: Invasive mechanical ventilation; CPAP: Continuous positive airway pressure; NIPPV: Noninvasive positive pressure ventilation; BiPAP: Bilevel positive airway pressure; OT: Oxygen therapy; NTO: Nasal tube oxygen; HFNC: High flow nasal cannula

Ethics

This study was approved by the Institutional Review Board (IRB) of The Third Affiliated Hospital of Guangzhou Medical University.

Consent

The requirement for informed consent was waived since it was a retrospective study.

Data availability

All the data generated or analysed during this study are included in this published article.

Conflict of interest

The authors declare that they have no competing interests.

Funding

Not applicable

Author contributions

XZ, JL and JSD conceptualised and designed the study, drafted the initial manuscript, and critically reviewed and revised the manuscript; QC, JL and JSD designed the data collection instruments, collected the data, conducted the initial analyses, and critically reviewed and revised the manuscript; and JSD critically reviewed and revised the manuscript. All the authors approved the final manuscript.

Acknowledgements

Not applicable

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Table 1 to 6 are available in the Supplementary Files section.

No competing interests reported.

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Differences in Risk Factors and Predictors of Preterm Twin Infants with Bronchopulmonary Dysplasia: A retrospective study

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Abstract

Background

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Background

Methods

Study design and participants

Study factors

Ethics

Statistical analysis

Results

Patients characteristics

Effect of complications in twin pairs with BPD

Effect of treatment in twin pairs with BPD

Effect of interventions in twin pairs with BPD

Discussion

Conclusion

Abbreviations

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References

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Supplementary Files

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