Abstract
Background: Over the years, bronchopulmonary dysplasia (BPD) affects the pulmonary function of infants, resulting in chronic health burdens for infants and their families. The aim of this scoping review was to screen available evidence regarding perinatal risk factors associated with the development and severity of BPD. Methods: The eligibility criteria of the studies were year of publication between 2016 and 2021; setting of a developed country; English or Japanese as the study language; and randomized controlled, cohort, or case-control design. The titles and abstracts of the studies were screened by independent reviewers. Results: Of 8189 eligible studies, 3 were included for severe BPD and 26 were included for moderate BPD. The risk factors for severe BPD were male sex, iatrogenic preterm birth, maternal hypertensive disorders of pregnancy (HDP), low gestational age, small-for-gestational-age (SGA) birth weight, mechanical ventilation on day 1, and need for patent ductus arteriosus (PDA) management. The risk factors for moderate or severe BPD included male sex, premature rupture of membranes, clinical chorioamnionitis, maternal HDP, SGA birth weight, bubbly/cystic appearance on X-ray, and PDA management. Conclusions: We identified several risk factors for BPD. We plan to confirm the validity of the new classification using the existing dataset.
Keywords: bronchopulmonary dysplasia, scoping review, premature, neonates
1. Introduction
Bronchopulmonary dysplasia (BPD) is one of the most important chronic morbidities associated with prematurity [1,2]. It requires prolonged respiratory support and causes airway hypersensitivity [3] and obstructive pulmonary disease [4], resulting in an increased incidence of re-hospitalization [5], neurodevelopmental impairment [6], and pulmonary hypertension [7]. Over the years, these events have resulted in considerable chronic health burdens for infants and their families [8]. Due to significant improvements in the long-term prognosis of extremely premature infants [9], the number of BPD cases has increased. To avoid health deterioration and serious sequelae, it is important to identify the risk factors of BPD in premature infants and explore better prophylactic and treatment strategies for BPD.
Since BPD affects pulmonary function and neurodevelopmental outcomes, a classification that can be used to predict long-term prognosis is required. The BPD classification proposed in 2001 by the National Institute of Child Health and Human Development (NICHD) [10], which is based on clinical treatments, such as oxygen and ventilatory support, is widely used. However, the association between severity based on the NICHD classification and the long-term prognosis of infants is unclear, partly because the NICHD classification is consensus-based [11]. In 1992, a BPD classification based on etiology and chest X-ray findings was introduced in Japan [12]. An association between the Japanese classification and long-term outcomes has been reported [13], but to date, it is popular only in Japan [14]. We expect that unknown factors will fill the gaps in BPD definitions by combining the NICHD classification and the Japanese pathophysiology-based classification. Furthermore, the phenotype of BPD has changed since the introduction of antenatal corticosteroid and surfactant replacement therapy [15], and more premature newborns are managed using non-invasive positive pressure ventilation [16,17]. New modalities of respiratory support, such as the use of high-flow nasal cannulas, have also become popular [18]. Therefore, we believe that the Japanese pathophysiology-based BPD classification also needs to be revised to better reflect changes in phenotype and management [19].
We hope to develop a new pathophysiology-based BPD classification based on our original classification, which is internationally acceptable. The aim of this scoping review was to screen available evidence and identify perinatal risk factors associated with the development and severity of BPD to establish a novel BPD classification that can be used to predict long-term prognosis.
2. Materials and Methods
2.1. Search and Selection of Studies
With the aid of knowledgeable librarians, we created a search plan to locate eligible studies in PubMed and the Japanese database Ichushi Web. A search was conducted in October 2021 with no restrictions on date, time, language, document type, or publication status. Keywords were identified from experts’ opinions, literature review, controlled vocabulary (Cumulative Index to Nursing and Allied Health Literature Headings, Medical Subject Headings, Excerpta Medica Tree), and a review of primary search results. To obtain all search outcome results and avoid poor reporting of outcomes, we did not limit the search in any way. The search strategy was developed with the assistance of a medical information specialist.
2.2. Eligibility Criteria
Articles that met the following eligibility criteria were included: (1) publication between January 2002 and August 2021; (2) setting of a developed country; (3) English or Japanese as the study language; (4) randomized controlled, prospective/retrospective cohort, or case-control study design; (5) extremely premature infants born before 28 weeks of gestation as study participants; and (6) endpoint of severe BPD according to the NICHD classification as an indicator of poor respiratory prognosis. Since we considered the development in the pathological evaluation and intervention/treatment methods of BPD and the change in the risk factors of BPD over the last 20 years, we only included articles published between January 2016 and August 2021. Regarding the secondary objective, we included studies that involved participants with birth weight < 1500 g or gestational age (GA) < 32 weeks and with endpoint of moderate or severe BPD according to the NICHD classification or combined results of BPD or death. The following types of articles were excluded from the review: (1) letters, editorials, commentaries, unpublished manuscripts, dissertations, government reports, books and book chapters, conference proceedings, meeting abstracts, lectures and addresses, and consensus development statements; (2) articles with <500 registered newborns; (3) articles reported by countries with United Nations Human Development Index < 0.8; and (4) animal studies.
2.3. Selection of Sources of Evidence
We used the web application Rayyan (http://rayyan.qcri.org; accessed on 1 January 2022) to speed up the selection process of studies for inclusion in this scoping review. The search results were de-duplicated using EndNote 20 and sent to four researchers for screening and confirmation. Four authors (S.K., M.I., M.S., and N.M.) independently screened all the titles and abstracts to exclude non-eligible trials. Disagreements between the four authors were discussed and resolved with the assistance of another reviewer. We then conducted a full-text review of potentially relevant articles. Disagreements between the reviewers were discussed, and decisions regarding selection were made by consensus. The reference lists of the included articles were screened for primary studies that were missed by the search strategy. Following a full-text review, data (including data on the risk factors of BPD) were extracted from all selected studies. We attempted to contact the author (HA) to conduct an additional study and provide the data [20].
2.4. Data Charting
At least two reviewers independently charted the data of the included studies using an Excel data extraction form developed for this study, and they discussed the results. The following data were extracted: author information, title, journal, year of publication, identified risk factors, study design, and participants. The review protocol was published [21] and registered on the University Hospital Medical Information Network Clinical Trial Registry (registration number: UMIN000045529). This scoping review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review Guideline [22].
3. Results
3.1. Risk Factors of Severe BPD
Of the 8189 eligible studies, three were included for risk factors of severe BPD (Figure 1).
Figure 1.
Study flow chart.
The investigated prenatal risk factors of severe BPD included male sex [23], iatrogenic preterm birth (result of induced labor or a cesarean section before labor and/or rupture of membranes) [24], maternal hypertensive disorders of pregnancy (HDP) [23], low GA [23], and small-for-gestational-age (SGA) birth weight [23] (Table 1). Male sex (adjusted odds ratio [aOR]: 1.75, 95% confidence interval [CI]: 1.22–2.49), iatrogenic preterm birth (aOR: 1.90, 95% CI: 1.10–3.26), maternal HDP (aOR: 2.18; 95% CI: 1.45–3.28), low GA (aOR: 1.36, 95% CI: 1.19–1.55), and SGA birth weight (aOR: 3.25, 95% CI: 1.91–5.54) were found to be associated with a high risk of BPD.
Table 1.
Prenatal risk factors of severe BPD.
| Risk Factor | Number of Studies with Positive Association/Number of Studies That Evaluated Risk Factors | aOR or RR* |
95% CI | Author, Year | Country | Study Design | Number of Participants | Patient Characteristic | BPD Definition | Reference Number |
|---|---|---|---|---|---|---|---|---|---|---|
| Male sex | 1/1 | 1.75 | 1.22–2.49 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] |
| Iatrogenic preterm birth | 1/1 | 1.90 | 1.10–3.26 | Fritz, T., 2018 | Sweden | Prospective cohort study | 737 | Birth at <27 wks GA | need for ≥30% O2 at 36 wks PMA | [24] |
| HDP | 1/1 | 2.18 | 1.45–3.28 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] |
| Low GA | 1/1 | 1.36 | 1.19–1.55 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] |
| SGA birth weight | 1/1 | 3.25 | 1.91–5.54 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] |
BPD: bronchopulmonary dysplasia, aOR: adjusted odds ratio, RR: relative risk, CI: confidence interval, HDP: hypertensive disorders of pregnancy, GA: gestational age, SGA: small for gestational age, wks: weeks, PMA: postmenstrual age.
The investigated postnatal risk factors of severe BPD included mechanical ventilation on the first day after birth and the need for patent ductus arteriosus (PDA) management [23,25] (Table 2). Mechanical ventilation on the first day after birth was found to be associated with the onset of BPD (aOR: 2.84, 95% CI: 1.54–5.24). Furthermore, symptomatic PDA had a negative effect on BPD onset (aOR: 2.53, 95% CI: 1.41–4.53), but prophylactic treatment of PDA failed to show efficacy in BPD prophylaxis (aOR: 0.98, 95% CI: 0.53–1.81).
Table 2.
Postnatal risk factors of severe BPD.
| Risk Factor | Number of Studies with Positive Association/Number of Studies That Evaluated Risk Factors | aOR or RR* |
95% CI | Author, Year | Country | Study Design | Number of Participants | Patient Characteristic | BPD Definition | Reference Number |
|---|---|---|---|---|---|---|---|---|---|---|
| Mechanical ventilation on first day after birth | 1/1 | 2.84 | 1.54–5.24 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] |
| Prophylactic treatment for PDA | 0/1 | 0.98 | 0.53–1.81 | Shin, J., 2021 | Korea | Prospective cohort study | 2303 | Birth at <28 wks GA | need for ≥30% O2 at 36 wks PMA | [25] |
| Need for PDA management | 1/1 | 2.53 | 1.41–4.53 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] |
BPD: bronchopulmonary dysplasia, aOR: adjusted odds ratio, RR: relative risk, CI: confidence interval, PDA: patent ductus arteriosus, wks: weeks, GA: gestational age, wks: weeks, PMA: postmenstrual age.
With our original search settings, the number of studies that investigated the association between severe BPD and various factors was small. Therefore, we revisited our original settings and adjusted the conditions (i.e., birth weight < 1500 g or GA < 32 weeks), any BPD severity, or combined results of BPD or death.
3.2. Risk Factors for Moderate or Severe BPD
When the target infants had birth weight < 1500 g or GA < 32 weeks and the outcome of moderate or severe BPD, the investigated prenatal risk factors of BPD included infant sex [23,26,27,28], twins [20,26,29], delivery method [24,26,29], maternal body mass index [30], oligohydramnios [29], maternal docosahexaenoic acid (DHA) supplementation [31], antenatal corticosteroid therapy [26,29,32], premature rupture of membranes (PROM) [26,29], pathological chorioamnionitis [20,27], clinical chorioamnionitis [26,33], HDP [20,23,27,34], antepartum hemorrhage [35], GA [20,23,26,27,29,33], infant birth weight [20,26,29,33], SGA birth weight [20,23,27,33,36,37,38] and large-for-gestational-age birth weight [39] (Table 3). Male infants had a higher risk of BPD than female infants (four studies reported a positive association, and four studies evaluated the risk factors; i.e., 4/4, aOR: 1.75, 95% CI: 1.22–2.49 [23], aOR: 1.42, 95% CI: 1.32–1.53 [26], aOR: 1.39, 95% CI: 1.11–1.75 [27], aOR: 1.28, 95% CI: 1.06–1.54 [28]). PROM (2/2, aOR: 1.49, 95% CI: 1.04–2.14 [29], aOR: 1.11, 95% CI: 1.02–1.20 [26]), and pathological/clinical chorioamnionitis (4/4, aOR: 1.53, 95% CI: 1.21–1.94 [27]], aOR: 1.16, 95% CI: 1.04–1.30 [20], aOR: 1.34, 95% CI: 1.23–1.45 [33], aOR: 1.25, 95% CI: 1.14–1.37 [26]) tended to increase the risk of BPD. The association between SGA birth weight and BPD has been extensively studied, and it was reported in several studies that SGA birth weight is a risk factor for BPD (10/10, aOR: 5.65, 95% CI: 2.42–13.19 [27], aOR: 3.56, 95% CI: 3.04–4.18 [36], aOR: 3.35, 95% CI: 2.65–4.22 [37], aOR: 3.25, 95% CI: 1.91–5.54 [23], aOR: 2.82, 95% CI: 2.29–3.49 [36], aOR: 2.77, 95% CI: 2.23–3.43 [37], aOR: 1.84, 95% CI: 1.30–2.60 [36], aOR: 1.73, 95% CI: 1.56–1.91 [33], aOR: 1.30, 95% CI: 1.08.–1.54 [20], relative risk: 1.30, 95% CI: 1.20–1.40 [38]).
Table 3.
Prenatal risk factors of moderate or severe BPD.
| Risk Factor | Number of Studies with positive Association /Number of Studies that evaluated Risk Factors |
aOR or RR* |
95% CI | Author, Year | Country | Study Design | Number of Participants |
Patient Characteristic | BPD Definition | Reference Number |
|---|---|---|---|---|---|---|---|---|---|---|
| Male sex | 4/4 | 1.75 | 1.22–2.49 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] |
| 1.42 | 1.32–1.53 | Ushida, T., 2021 | Japan | Retrospective cohort study | 31,157 | Birth at 22–31 wks GA with VLBW | need for >21% O2 at 36 wks PMA | [26] | ||
| 1.39 | 1.11–1.75 | Shin, S. H., 2020 | Korea | Prospective cohort study | 2276 | Birth at <30 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [27] | ||
| 1.28 | 1.06–1.54 | Shim, S. Y., 2017 | Korea | Retrospective cohort study | 1839 | Birth at 23–29 wks GA with VLBW | need for >21% O2 | [28] | ||
| Monochorionic twins | 1/1 | 1.34 | 1.18–1.52 | Ushida, T., 2021 | Japan | Retrospective cohort study | 31,157 | Birth at 22–31 wks GA with VLBW | need for >21% O2 at 36 wks PMA | [26] |
| Multiple birth | 0/2 | 0.82 | 0.71–0.94 | Arai, H., 2019 | Japan | Retrospective cohort study | 15,480 | BPD, birth at <28 wks GA with BW < 1500 g |
need for >21% O2 or positive pressure support at 36 wks PMA | [20] ** |
| 0.62 | 0.40–0.96 | Park, J. H., 2021 | Korea | Retrospective cohort study | 884 | Birth at 23–27 wks GA with PROM | need for >21% O2 or positive pressure support at 36 wks PMA | [29] | ||
| Iatrogenic preterm birth | 1/1 | 1.90 | 1.10–3.26 | Fritz, T., 2018 | Sweden | Prospective cohort study | 737 | Birth at <27 wks GA | need for ≥30% O2 at 36 wks PMA | [24] |
| Vaginal delivery | 0/1 | 0.85 | 0.78–0.94 | Ushida, T., 2021 | Japan | Retrospective cohort study | 31,157 | Birth at 22–31 wks GA with VLBW | need for >21% O2 at 36 wks PMA | [26] |
| CS | 0/1 | 1.39 | 0.95–2.03 | Park, J. H., 2021 | Korea | Retrospective cohort study | 884 | Birth at 23–27 wks GA with PROM | need for >21% O2 or positive pressure support at 36 wks PMA | [29] |
| High maternal BMI | 0/1 | 1.22 | 0.96–1.56 | Lee, B. K., 2021 | Korea | Retrospective cohort study | 7348 | Birth at 25–30 wks GA with VLBW | need for ≥30% O2 or positive pressure support at 36 wks PMA | [30] |
| Low maternal BMI | 1/1 | 1.44 | 1.06–1.96 | Lee, B. K., 2021 | Korea | Retrospective cohort study | 7348 | Birth at 25–30 wks GA with VLBW | need for ≥30% O2 or positive pressure support at 36 wks PMA | [30] |
| Oligohydramnios | 0/1 | 1.13 | 0.76–1.69 | Park, J. H., 2021 | Korea | Retrospective cohort study | 884 | Birth at 23–27 wks GA with PROM | need for >21% O2 or positive pressure support at 36 wks PMA | [29] |
| Maternal docosahexaenoic acid supplementation | 0/1 | 0.91 * | 0.80–1.04 | Marc, I., 2020 | Canada | RCT | 528 | Birth at 29 wks GA | need for >21% O2 at 36 wks PMA | [31] |
| Antenatal corticosteroid therapy | 0/2 | 0.96 | 0.90–1.03 | Travers, C. P., 2018 | USA | Retrospective cohort study | 9715 | Birth at 22–28 wks GA with BW > 400 g |
need for >21% O2 at 36 wks PMA | [32] |
| 0.78 | 0.41–1.49 | Park, J. H., 2021 | Korea | Retrospective cohort study | 884 | Birth at 23–27 wks GA with PROM | need for >21% O2 or positive pressure support at 36 wks PMA | [29] | ||
| No antenatal corticosteroid therapy | 0/1 | 0.72 | 0.67–0.78 | Ushida, T., 2021 | Japan | Retrospective cohort study | 31,157 | Birth at 22–31 wks GA with VLBW | need for >21% O2 at 36 wks PMA | [26] |
| PROM | 2/2 | 1.49 | 1.04–2.14 | Park, J. H., 2021 | Korea | Retrospective cohort study | 884 | Birth at 23–27 wks GA with PROM | need for >21% O2 or positive pressure support at 36 wks PMA | [29] |
| 1.11 | 1.02–1.20 | Ushida, T., 2021 | Japan | Retrospective cohort study | 31,157 | Birth at 22–31 wks GA with VLBW | need for >21% O2 at 36 wks PMA | [26] | ||
| Pathological chorioamnionitis | 2/2 | 1.53 | 1.21–1.94 | Shin, S. H., 2020 | Korea | Prospective cohort study | 2276 | Birth at <30 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [27] |
| 1.16 | 1.04–1.30 | Arai, H., 2019 | Japan | Retrospective cohort study | 15,480 | BPD, birth at <28 wks GA with BW < 1500 g |
need for >21% O2 or positive pressure support at 36 wks PMA | [20] ** | ||
| Clinical chorioamnionitis | 2/2 | 1.34 | 1.23–1.45 | Nakashima, T., 2020 | Japan | Retrospective cohort study | 17,126 | Birth at 22–27 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [33] |
| 1.25 | 1.14–1.37 | Ushida, T., 2021 | Japan | Retrospective cohort study | 31,157 | Birth at 22–31 wks GA with VLBW | need for >21% O2 at 36 wks PMA | [26] | ||
| HDP | 3/4 | 2.18 | 1.45–3.28 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] |
| 1.47 | 1.03–2.12 | Shin, S. H., 2020 | Korea | Prospective cohort study | 2276 | Birth at <30 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [27] | ||
| 1.33 | 1.09–1.61 | Arai, H., 2019 | Japan | Retrospective cohort study | 15,480 | BPD, birth at <28 wks GA with BW < 1500 g |
need for >21% O2 or positive pressure support at 36 wks PMA | [20] ** | ||
| 0.75 | 0.58–0.97 | Sloane, A. J., 2019 | USA | Retrospective cohort study | 5456 | VLBW | need for >21% O2 at 36 wks PMA | [34] | ||
| Antepartum hemorrhage | 0/1 | 1.19 | 0.98–1.43 | Klinger, G., 2021 | Israel | Retrospective cohort study | 33,627 | Birth at 24–31 wks GA with VLBW | need for >21% O2 at 36 wks PMA | [35] |
| Low GA | 1/1 | 1.36 | 1.19–1.55 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] |
| High GA | 0/3 | 0.97 | 0.96–0.97 | Ushida, T., 2021 | Japan | Retrospective cohort study | 31,157 | Birth at 22–31 wks GA with VLBW | need for >21% O2 at 36 wks PMA | [26] |
| 0.78 | 0.62–0.99 | Park, J. H., 2021 | Korea | Retrospective cohort study | 884 | Birth at 23–27 wks GA with PROM | need for >21% O2 or positive pressure support at 36 wks PMA | [29] | ||
| 0.67 | 0.63–0.72 | Shin, S. H., 2020 | Korea | Prospective cohort study | 2276 | Birth at <30 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [27] | ||
| GA < 26 wks | 2/2 | 2.68 | 2.47–2.91 | Nakashima, T., 2020 | Japan | Retrospective cohort study | 17,126 | Birth at 22–27 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [33] |
| 1.30 | 1.07–1.47 | Arai, H., 2019 | Japan | Retrospective cohort study | 15,480 | BPD, birth at <28 wks GA with BW < 1500 g |
need for >21% O2 or positive pressure support at 36 wks PMA | [20] ** | ||
| High BW | 0/2 | 1.00 | 1.00–1.00 | Park, J. H., 2021 | Korea | Retrospective cohort study | 884 | Birth at 23–27 wks GA with PROM | need for >21% O2 or positive pressure support at 36 wks PMA | [29] |
| 0.77 | 0.76–0.79 | Ushida, T., 2021 | Japan | Retrospective cohort study | 31,157 | Birth at 22–31 wks GA with VLBW | need for >21% O2 at 36 wks PMA | [26] | ||
| BW < 700 g | 1/1 | 1.71 | 1.43–2.06 | Arai, H., 2019 | Japan | Retrospective cohort study | 15,480 | BPD, birth at <28 wks GA with BW < 1500 g |
need for >21% O2 or positive pressure support at 36 wks PMA | [20] ** |
| BW < 750 g | 1/1 | 3.14 | 2.90–3.41 | Nakashima, T., 2020 | Japan | Retrospective cohort study | 17,126 | Birth at 22–27 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [33] |
| SGA BW | 10/10 | 5.65 | 2.42–13.19 | Shin, S. H., 2020 | Korea | Prospective cohort study | 2276 | Birth at <30 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [27] |
| 3.56 | 3.04–4.18 | Boghossian, N. S., 2018 |
USA | Retrospective cohort study | data not available |
Birth at 27 wks GA | need for >21% O2 at 36 wks PMA | [36] | ||
| 3.35 | 2.65–4.22 | Aldana-Aguirre, J. C., 2019 |
Canada | Retrospective cohort study | 5309 | PDA, birth at <33 wks GA | need for >21% O2 at 36 wks PMA | [37] | ||
| 3.25 | 1.91–5.54 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] | ||
| 2.82 | 2.29–3.49 | Boghossian, N. S., 2018 |
USA | Retrospective cohort study | data not available |
Birth at 29 wks GA | need for >21% O2 at 36 wks PMA | [36] | ||
| 2.77 | 2.23–3.43 | Aldana-Aguirre, J. C., 2019 |
Canada | Retrospective cohort study | 16,998 | Birth at <33 wks GA | need for >21% O2 at 36 wks PMA | [37] | ||
| 1.84 | 1.30–2.60 | Boghossian, N. S., 2018 |
USA | Retrospective cohort study | data not available |
Birth at 23 wks GA | need for >21% O2 at 36 wks PMA | [36] | ||
| 1.73 | 1.56–1.91 | Nakashima, T., 2020 | Japan | Retrospective cohort study | 17,126 | Birth at 22–27 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [33] | ||
| 1.29 | 1.08–1.54 | Arai, H., 2019 | Japan | Retrospective cohort study | 15,480 | BPD, birth at <28 wks GA with BW < 1500 g |
need for >21% O2 or positive pressure support at 36 wks PMA | [20] ** | ||
| 1.30 * | 1.20–1.40 | Monier, I., 2017 | France | Retrospective cohort study | 2505 | Birth at <32 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [38] | ||
| LGA BW | 0/1 | 0.71 | 0.68–0.73 | Boghossian, N. S., 2018 |
USA | Retrospective cohort study | 156,587 | Birth at 22–29 wks GA | need for >21% O2 at 36 wks PMA | [39] |
** reanalyzed and extracted as risk factors. BPD: bronchopulmonary dysplasia, aOR: adjusted odds ratio, RR: relative risk, CI: confidence interval, CS: cesarean section, BMI: body mass index, PROM: premature rupture of membranes, pPROM: preterm premature rupture of membranes, HDP: hypertensive disorders of pregnancy, wks: weeks, GA: gestational age, BW: birth weight, VLBW: very low birth weight, SGA: small for gestational age, LGA: large for gestational age, PMA: postmenstrual age.
The investigated postnatal risk factors of moderate or severe BPD included delayed cord clamping [40,41], resuscitation [33,42], respiratory management [23,33], bubbly/cystic appearance on X-ray [20], respiratory distress syndrome (RDS)/surfactant administration [20,23,27,33,43,44], caffeine administration [45], sivelestat administration [46], PDA management [23,25,27,33,47], infections [33], respiratory flora [48], breast milk [49], and infant DHA supplementation [50] (Table 4). Bubbly/cystic appearance on X-rays has been shown to have an adverse effect on BPD onset (aOR: 2.49, 95% CI: 2.24–2.77) [20]. Regarding RDS, two of the four extracted articles reported it as a risk factor of BPD (2/4, aOR: 2.44, 95% CI: 1.68–3.54 [23], aOR: 1.62, 95% CI: 0.96–2.72 [27], aOR: 1.24, 95% CI: 1.13–1.37 [33], aOR: 0.84, 95% CI: 0.74–0.94 [20]), but it was also reported that less invasive surfactant administration suppressed BPD onset (aOR: 0.55, 95% CI: 0.49–0.62) [44]. Most studies on PDA have reported that PDA has an adverse effect on BPD onset (3/4, aOR: 2.53, 95% CI: 1.41–4.53 [23] aOR: 2.30, 95% CI: 1.82–2.90 [27], aOR: 1.30, 95% CI: 1.20–1.41 [33], aOR: 0.47, 95% CI: 0.28–1.80 [47]).
Table 4.
Postnatal risk factors of moderate or severe BPD.
| Risk Factor | Number of Studies with positive Association /Number of Studies That Evaluated Risk Factors |
aOR or RR* |
95% CI | Author, Year | Country | Study Design | Number of Participants |
Patient Characteristic | BPD Definition | Reference Number |
|---|---|---|---|---|---|---|---|---|---|---|
| Delayed cord clamping | 0/2 | 1.04 * | 0.95–1.14 | Tarnow-Mordi, W., 2017 | Australia | Randomized clinical trial | 1634 | Birth at <32 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [40] |
| 0.99 | 0.86–1.14 | Lodha, A., 2019 | Canada | Retrospective cohort study | 4680 | Birth at 22–28 wks GA | need for >21% O2 at 36 wks PMA | [41] | ||
| Extensive cardiopulmonary resuscitation | 1/1 | 1.68 | 1.19–2.37 | Shukla, V., 2020 | Canada | Retrospective cohort study | 3633 | Birth at <26 wks GA | need for >21% O2 at 36 wks PMA or at discharge from the participating unit |
[42] |
| Intubation at birth | 1/1 | 1.84 | 1.64–2.07 | Nakashima, T., 2020 | Japan | Retrospective cohort study | 17,126 | Birth at 22–27 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [33] |
| Mechanical ventilation on first day after birth | 1/1 | 2.84 | 1.54–5.24 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] |
| Supplemental oxygen for >4 weeks | 1/1 | 6.98 | 8.27–11.72 | Nakashima, T., 2020 | Japan | Retrospective cohort study | 17,126 | Birth at 22–27 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [33] |
| Invasive ventilation for >4 weeks | 1/1 | 4.82 | 4.39–5.30 | Nakashima, T., 2020 | Japan | Retrospective cohort study | 17,126 | Birth at 22–27 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [33] |
| Non-invasive positive pressure ventilation for >4 weeks | 1/1 | 1.11 | 1.03–1.20 | Nakashima, T., 2020 | Japan | Retrospective cohort study | 17,126 | Birth at 22–27 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [33] |
| Bubbly/cystic appearance on X-ray | 1/1 | 2.49 | 2.24–2.77 | Arai, H., 2019 | Japan | Retrospective cohort study | 15,480 | BPD, birth at <28 wks GA with BW < 1500 g |
need for >21% O2 or positive pressure support at 36 wks PMA | [20] ** |
| RDS/surfactant administration | 2/4 | 2.44 | 1.68–3.54 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] |
| 1.62 | 0.96–2.72 | Shin, S. H., 2020 | Korea | Prospective cohort study | 2276 | Birth at <30 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [27] | ||
| 1.24 | 1.13–1.37 | Nakashima, T., 2020 | Japan | Retrospective cohort study | 17,126 | Birth at 22–27 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [33] | ||
| 0.84 | 0.74–0.94 | Arai, H., 2019 | Japan | Retrospective cohort study | 15,480 | BPD, birth at <28 wks GA with BW < 1500 g |
need for >21% O2 or positive pressure support at 36 wks PMA | [20] ** | ||
| Late surfactant administration | 1/1 | 1.55 | 1.20–2.00 | Stritzke, A., 2018 | Canada | Retrospective cohort study | 2512 | Birth at <28 wks GA | need for >21% O2 at 36 wks PMA | [43] |
| Less invasive surfactant administration | 0/1 | 0.55 | 0.49–0.62 | Härtel, C., 2018 | Germany | Retrospective cohort study | 7533 | Birth at 22–29 wks GA with BW < 1500 g |
need for >21% O2 or positive pressure support at 36 wks PMA | [44] |
| Early caffeine administration | 0/1 | 0.61 | 0.45–0.81 | Lodha, A., 2019 | Canada | Retrospective cohort study | 3993 | Birth at <29 wks GA | need for >21% O2 at 36 wks PMA | [45] |
| Sivelestat administration | 0/1 | 0.83 | 0.53–1.30 | Ogawa, R., 2017 | Japan | Retrospective cohort study | 1031 | Birth at <28 wks GA with BW < 1000 g |
need for >21% O2 at 28 days old or 36 wks PMA | [46] |
| Prophylactic treatment for PDA | 0/1 | 0.98 | 0.53–1.81 | Shin, J., 2021 | Korea | Prospective cohort study | 2303 | Birth at <28 wks GA | need for ≥30% O2 at 36 wks PMA | [25] |
| Need for PDA management | 3/4 | 2.53 | 1.41–4.53 | Tagliaferro, T., 2019 | USA | Retrospective cohort study | 1218 | Birth at 23–28 wks GA | need for ≥30% O2 at 36 wks PMA | [23] |
| 2.30 | 1.82–2.90 | Shin, S. H., 2020 | Korea | Prospective cohort study | 2276 | Birth at <30 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [27] | ||
| 1.30 | 1.20–1.41 | Nakashima, T., 2020 | Japan | Retrospective cohort study | 17,126 | Birth at 22–27 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [33] | ||
| 0.47 | 0.28–1.80 | Mohamed, M. A., 2017 | USA | Retrospective cohort study | 643 | BW < 1500 g | need for >21% O2 at 36 wks PMA | [47] | ||
| Sepsis | 1/1 | 1.50 | 1.33–1.69 | Nakashima, T., 2020 | Japan | Retrospective cohort study | 17,126 | Birth at 22–27 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [33] |
| Normal respiratory flora | 0/1 | 0.58 | 0.34–0.99 | Antoine, J., 2020 | Australia | Retrospective cohort study | 1054 | Birth at <32 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [48] |
| Breast milk | 0/1 | 0.40 | 0.27–0.67 | Dicky, O., 2017 | France | Prospective cohort study | 926 | Birth at <32 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [49] |
| Enteral docosahexaenoic acid supplementation | 1/1 | 1.13 | 1.02–1.25 | Collins, C. T., 2017 | Australia | RCT | 1273 | Birth at <29 wks GA | need for >21% O2 or positive pressure support at 36 wks PMA | [50] |
** Reanalyzed and extracted as risk factors. BPD: bronchopulmonary dysplasia, aOR: adjusted odds ratio, RR: relative risk, CI: confidence interval, RDS: respiratory distress syndrome, PDA: patent ductus arteriosus, RCT: randomized clinical trial, wks: weeks, GA: gestational age, BW: birth weight, PMA: postmenstrual age.
Table 5 and Table 6 show the extracted risk factors when the outcomes were combined results of BPD or death [51,52,53]. Male sex (1/1), low GA (1/1), SGA birth weight (1/1), and RDS (1/1) were selected as risk factors for moderate or severe BPD or death.
Table 5.
Prenatal risk factors of moderate or severe BPD or death.
| Risk Factor | Number of Studies with Positive Association/Number of Studies That Evaluated Risk Factors | aOR or RR* |
95% CI | Author, Year | Country | Study Design | Number of Participants | Patient Characteristic | BPD Definition | Reference Number |
|---|---|---|---|---|---|---|---|---|---|---|
| Male sex | 1/1 | 1.37 | 1.19–1.58 | Jung, Y. H., 2019 | Korea | Prospective cohort study | 4940 | Birth at 23–31 wks GA | need for >21% O2 at 36 wks PMA | [51] |
| Oligohydramnios | 0/1 | 1.22 | 1.00–1.50 | Jung, Y. H., 2019 | Korea | Prospective cohort study | 4940 | Birth at 23–31 wks GA | need for >21% O2 at 36 wks PMA | [51] |
| LGA birth weight | 1/1 | 1.70 | 1.63–1.77 | Jung, Y. H., 2019 | Korea | Prospective cohort study | 4940 | Birth at 23–31 wks GA | need for >21% O2 at 36 wks PMA | [51] |
| SGA z-score | 1/1 | 1.35 | 1.20–1.52 | Jung, Y. H., 2019 | Korea | Prospective cohort study | 4940 | Birth at 23–31 wks GA | need for >21% O2 at 36 wks PMA | [51] |
| Short length at birth z-score | 1/1 | 1.25 | 1.14–1.37 | Jung, Y. H., 2019 | Korea | Prospective cohort study | 4940 | Birth at 23–31 wks GA | need for >21% O2 at 36 wks PMA | [51] |
BPD: bronchopulmonary dysplasia, aOR: adjusted odds ratio, RR: relative risk, CI: confidence interval, LGA: large for gestational age, SGA: small for gestational age, wks: weeks, GA: gestational age, PMA: postmenstrual age.
Table 6.
Postnatal risk factors of moderate or severe BPD or death.
| Risk Factor | Number of Studies with Positive Association/Number of Studies That Evaluated Risk Factors | aOR or RR* |
95% CI | Author, Year | Country | Study Design | Number of Participants | Patient Characteristic | BPD Definition | Reference Number |
|---|---|---|---|---|---|---|---|---|---|---|
| Hypothemia | 0/1 | 1.03 | 0.64–1.68 | Jensen, C. F., 2017 | Denmark | Retrospective cohort study | 808 | Birth at <32 wks GA | need for >21% O2 at 36 wks PMA | [52] |
| RDS | 1/1 | 1.90 | 1.46–2.48 | Jung, Y. H., 2019 | Korea | Prospective cohort study | 4940 | Birth at 23–31 wks GA | need for >21% O2 at 36 wks PMA | [51] |
| ≤48 hours of antibiotic therapy | 0/1 | 1.19 | 0.88–1.62 | Flannery, D. D., 2018 | USA | Retrospective cohort study | 4950 | Sepsis, birth at <32 wks GA with BW <1500 g | need for >21% O2 or positive pressure support at 36 wks PMA | [53] |
| 3–7 days of antibiotic therapy | 0/1 | 0.82 | 0.65–1.04 | Flannery, D. D., 2018 | USA | Retrospective cohort study | 4950 | Sepsis, birth at <32 wks GA with BW <1500 g | need for >21% O2 or positive pressure support at 36 wks PMA | [53] |
BPD: bronchopulmonary dysplasia, aOR: adjusted odds ratio, RR: relative risk, CI: confidence interval, RDS: respiratory distress syndrome, wks: weeks, GA: gestational age, BW: birth weight, PMA: postmenstrual age.
4. Discussion
To develop a new pathophysiology-based BPD classification that can be used to predict severe BPD early in life to facilitate early treatment, we conducted a scoping review and comprehensively evaluated the risk factors of BPD. We found that three previous studies were comparable to this study. The prenatal risk factors were male sex, iatrogenic preterm birth, maternal HDP, low GA, and SGA birth weight, and the postnatal risk factors were mechanical ventilation on the first day after birth and the need for PDA management. The risk factors of moderate or severe BPD included prenatal factors, such as male sex and SGA birth weight, and postnatal factors, such as RDS and PDA treatment. In addition, three of the included studies were conducted in Japan, and the risk factors mentioned in the studies included chorioamnionitis and bubble/cystic appearance. As previously reported, there are multiple risk factors for BPD; therefore, we reckoned that multiple factors should be extracted in this scoping review.
Unlike the international BPD classification, which is based on treatment, the Japanese BPD classification is based on etiological factors (e.g., RDS, intrauterine infection) and bubbly/cystic appearance on chest X-ray [12]. Imaging practices in neonatal intensive care units have not evolved significantly since Northway et al. reported an overview of BPD. Hirata et al. reported that bubbly/cystic appearance on chest X-rays was associated with respiratory prognosis [13]. We also found that bubbly/cystic appearance on chest X-ray was a risk factor for moderate or severe BPD. Therefore, we consider bubbly/cystic appearance on chest X-ray as a factor that can be used to develop a new BPD classification that can be used to predict severe BPD early in life, thereby facilitating early treatment.
Male sex had been reported to be a risk factor for BPD even before the articles included in this scoping review were published [54,55,56,57], and the results of our review are comparable to those of previous studies. Many articles on the relationship between SGA birth weight and BPD were extracted. It has been reported that biological mechanisms such as placental dysfunction and deficiency of insulin growth factor, vascular endothelial growth factor (VEGF), and VEGF receptors, which result in intrauterine growth retardation, can lead to fetal lung growth retardation [58].
In this scoping review, there were many studies that reported RDS as a risk factor for moderate or severe BPD, but some studies had contrary reports. In Japan, many institutions are attempting to improve the diagnosis of RDS by incorporating the prediction of surfactant secretion using a stable microbubble test [59,60]. However, the latest European guidelines recommend that surfactants be administered for RDS if sustained positive pressure ventilation fails [61]. This recommendation takes into account physical and radiographic findings but not surfactant secretion. Moreover, considering that most extremely premature infants are administered surfactants after birth using different methods [62,63,64], RDS may no longer be a necessary factor in the future diagnosis of BPD in extremely premature infants.
There is yet no consensus on whether chorioamnionitis increases the odds of developing BPD [14,65,66,67]. PROM is regarded as the leakage of amniotic fluid before the onset of labor, and chorioamnionitis is an important factor [68]. It was suggested that the importance of chorioamnionitis in the diagnosis of BPD differs from country to country, and in this study, we found reviews of studies conducted in Japan and South Korea. Data on chorioamnionitis are extracted when a database is built in these two above-mentioned countries, which is an advantage. Pathological chorioamnionitis is thought to be associated with a high incidence of PROM and preterm birth [69]. However, symptoms of clinical chorioamnionitis and pathological chorioamnionitis are not always simultaneously present [70]. It was reported that the positive predictive value of pathological chorioamnionitis was high for uterine fundal tenderness and purulent or foul amniotic fluid or cervical discharge, but significantly low for maternal fever [71]. If chorioamnionitis is to be considered an onset factor of BPD, it may be necessary to decide on a more rigorous diagnostic method and selection criteria.
Due to factors such as pulmonary edema and endothelial injury because of increased pulmonary blood flow, increased risk of pulmonary hemorrhage, and the necessity of prolonged and aggressive ventilation, PDA is thought to have an adverse effect on the development of BPD [72]. Regarding PDA, there are various views on the diagnostic criteria, treatment methods, and indications for ligation. There are also reports that ibuprofen administration did not reduce the risk of developing BPD [73], or even increased it [74]. It is necessary to continue to focus on BPD prevention.
A limitation of this scoping review is the differences in the study design and patient characteristics between the articles. For practical reasons, this scoping review considered only articles written in English and Japanese. We also searched for articles in Japanese, but there were no such articles that were subject to review. Furthermore, due to the nature of the outlined search methodology, important published studies may have been omitted.
In conclusion, in this scoping review, we identified various prenatal and postnatal risk factors for moderate or severe BPD. Studies conducted in Japan and South Korea showed that chest X-ray findings and chorioamnionitis were predictors of BPD severity. These two factors should be combined to construct a new BPD classification that can be used to predict prognosis. In the future, we plan to use registry data to verify the prognosis predicted using the new BPD classification.
Acknowledgments
We would like to thank librarian Kuniko Sato for her searching support.
Author Contributions
This study was conceptualized by H.N., E.O. and F.N. All authors contributed to the scope and design of the review. E.O. developed our search strategy via consultation with a medical librarian at St. Luke’s International University. S.K., M.I., M.S. and N.M. performed screening, data charting and data synthesis of the studies. H.A. restatisticed the data from his article and provided it to us. M.I. prepared the first draft, and all other authors provided substantial input toward the development of the final version. E.O., F.N. and H.N. provided feedback on the methodology. All authors have read and agreed to the published version of the manuscript.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
Not applicable.
Conflicts of Interest
The authors have no conflict of interest to declare.
Funding Statement
This research is supported by the Research Program on Rare and Intractable Diseases, Health, Labor, and Welfare Sciences Research Grants (21FC0101).
Footnotes
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References
- 1.Shah P.S., Lui K., Sjörs G., Mirea L., Reichman B., Adams M., Modi N., Darlow B.A., Kusuda S., San Feliciano L., et al. Neonatal Outcomes of Very Low Birth Weight and Very Preterm Neonates: An International Comparison. J. Pediatr. 2016;177:144–152.e6. doi: 10.1016/j.jpeds.2016.04.083. [DOI] [PubMed] [Google Scholar]
- 2.Stoll B.J., Hansen N.I., Bell E.F., Shankaran S., Laptook A.R., Walsh M.C., Hale E.C., Newman N.S., Schibler K., Carlo W.A., et al. Neonatal Outcomes of Extremely Preterm Infants From the NICHD Neonatal Research Network. Pediatrics. 2010;126:443–456. doi: 10.1542/peds.2009-2959. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Motoyama E.K., Fort M.D., Klesh K.W., Mutich R.L., Guthrie R.D. Early Onset of Airway Reactivity in Premature Infants with Bronchopulmonary Dysplasia. Am. Rev. Respir. Dis. 1987;136:50–57. doi: 10.1164/ajrccm/136.1.50. [DOI] [PubMed] [Google Scholar]
- 4.Fawke J., Lum S., Kirkby J., Hennessy E., Marlow N., Rowell V., Thomas S., Stocks J. Lung function and respiratory symptoms at 11 years in children born extremely preterm: The EPICure study. Am. J. Respir. Crit. Care Med. 2010;182:237–245. doi: 10.1164/rccm.200912-1806OC. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Smith V.C., Zupancic J.A., McCormick M.C., Croen L.A., Greene J., Escobar G.J., Richardson D.K. Rehospitalization in the first year of life among infants with bronchopulmonary dysplasia. J. Pediatr. 2004;144:799–803. doi: 10.1016/j.jpeds.2004.03.026. [DOI] [PubMed] [Google Scholar]
- 6.Schmidt B., Asztalos E.V., Roberts R.S., Robertson C.M.T., Sauve R.S., Whitfield M.F. Impact of Bronchopulmonary Dysplasia, Brain Injury, and Severe Retinopathy on the Outcome of Extremely Low-Birth-Weight Infants at 18 Months: Results From the Trial of Indomethacin Prophylaxis in Preterms. JAMA. 2003;289:1124–1129. doi: 10.1001/jama.289.9.1124. [DOI] [PubMed] [Google Scholar]
- 7.Arjaans S., Haarman M.G., Roofthooft M.T.R., Fries M.W.F., Kooi E.M.W., Bos A.F., Berger R.M.F. Fate of pulmonary hypertension associated with bronchopulmonary dysplasia beyond 36 weeks postmenstrual age. Arch. Dis. Child.-Fetal Neonatal Ed. 2020;106:45–50. doi: 10.1136/archdischild-2019-318531. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Humayun J., Löfqvist C., Ley D., Hellström A., Gyllensten H. Systematic review of the healthcare cost of bronchopulmonary dysplasia. BMJ Open. 2021;11:e045729. doi: 10.1136/bmjopen-2020-045729. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Helenius K., Sjörs G., Shah P.S., Modi N., Reichman B., Morisaki N., Kusuda S., Lui K., Darlow B.A., Bassler D., et al. Survival in Very Preterm Infants: An International Comparison of 10 National Neonatal Networks. Pediatrics. 2017;140:e20171264. doi: 10.1542/peds.2017-1264. [DOI] [PubMed] [Google Scholar]
- 10.Jobe A.H., Bancalari E. Bronchopulmonary dysplasia. Am. J. Respir. Crit. Care Med. 2001;163:1723–1729. doi: 10.1164/ajrccm.163.7.2011060. [DOI] [PubMed] [Google Scholar]
- 11.Hines D., Modi N., Lee S.K., Isayama T., Sjörs G., Gagliardi L., Lehtonen L., Vento M., Kusuda S., Bassler D., et al. Scoping review shows wide variation in the definitions of bronchopulmonary dysplasia in preterm infants and calls for a consensus. Acta Paediatr. 2017;106:366–374. doi: 10.1111/apa.13672. [DOI] [PubMed] [Google Scholar]
- 12.Ogawa Y., Fujimura M., Goto A., Kawano T., Kondo T., Nakae N., Nishida A., Ohno T., Takeuchi Y., Togari H., et al. Epidemiology of Neonatal Chronic Lung Disease in Japan. Acta Paediatr Jpn. 1992;34:663–667. doi: 10.1111/j.1442-200X.1992.tb01028.x. [DOI] [PubMed] [Google Scholar]
- 13.Hirata K., Nishihara M., Shiraishi J., Hirano S., Matsunami K., Sumi K., Wada N., Kawamoto Y., Nishikawa M., Nakayama M., et al. Perinatal factors associated with long-term respiratory sequelae in extremely low birthweight infants. Arch. Dis. Child.-Fetal Neonatal Ed. 2015;100:F314–F319. doi: 10.1136/archdischild-2014-306931. [DOI] [PubMed] [Google Scholar]
- 14.Namba F., Fujimura M., Tamura M. Bubbly and cystic appearance in chronic lung disease: Is this diagnosed as Wilson-Mikity syndrome? Pediatr. Int. 2016;58:251–253. doi: 10.1111/ped.12901. [DOI] [PubMed] [Google Scholar]
- 15.Jobe A.J. The New BPD: An Arrest of Lung Development. Pediatr. Res. 1999;46:641. doi: 10.1203/00006450-199912000-00007. [DOI] [PubMed] [Google Scholar]
- 16.Hutchison A.A., Bignall S. Non-invasive positive pressure ventilation in the preterm neonate: Reducing endotrauma and the incidence of bronchopulmonary dysplasia. Arch. Dis. Child.-Fetal Neonatal Ed. 2008;93:F64–F68. doi: 10.1136/adc.2006.103770. [DOI] [PubMed] [Google Scholar]
- 17.Isayama T., Iwami H., McDonald S., Beyene J. Association of Noninvasive Ventilation Strategies With Mortality and Bronchopulmonary Dysplasia Among Preterm Infants: A Systematic Review and Meta-analysis. JAMA. 2016;316:611–624. doi: 10.1001/jama.2016.10708. [DOI] [PubMed] [Google Scholar]
- 18.Sand L., Szatkowski L., Kwok T.C., Sharkey D., A Todd D., Budge H., Ojha S. Observational cohort study of changing trends in non-invasive ventilation in very preterm infants and associations with clinical outcomes. Arch. Dis. Child.-Fetal Neonatal Ed. 2022;107:150–155. doi: 10.1136/archdischild-2021-322390. [DOI] [PubMed] [Google Scholar]
- 19.Ito M., Tomotaki S., Isayama T., Hara H., Hirata K., Arai H. The status of chronic lung disease diagnosis in Japan: Secondary publication. Pediatr. Int. 2022;64:e15184. doi: 10.1111/ped.15184. [DOI] [PubMed] [Google Scholar]
- 20.Arai H., Ito T., Ito M., Ota S., Takahashi T. The Neonatal Research Network of Japan Impact of chest radiography-based definition of bronchopulmonary dysplasia. Pediatr. Int. 2019;61:258–263. doi: 10.1111/ped.13786. [DOI] [PubMed] [Google Scholar]
- 21.Kato S., Ito M., Saito M., Miyahara N., Namba F., Ota E., Nakanishi H. Severe bronchopulmonary dysplasia in extremely premature infants: A scoping review protocol for identifying risk factors. BMJ Open. 2022;12:e062192. doi: 10.1136/bmjopen-2022-062192. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Tricco A.C., Lillie E., Zarin W., O’Brien K.K., Colquhoun H., Levac D., Moher D., Peters M.D., Horsley T., Weeks L., et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann. Intern. Med. 2018;169:467–473. doi: 10.7326/M18-0850. [DOI] [PubMed] [Google Scholar]
- 23.Tagliaferro T., Jain D., Vanbuskirk S., Bancalari E., Claure N. Maternal preeclampsia and respiratory outcomes in extremely premature infants. Pediatr. Res. 2019;85:693–696. doi: 10.1038/s41390-019-0336-5. [DOI] [PubMed] [Google Scholar]
- 24.Fritz T., Källén K., Marsál K., Jacobsson B. Outcome of extremely preterm infants after iatrogenic or spontaneous birth. Acta Obstet. Gynecol. Scand. 2018;97:1388–1395. doi: 10.1111/aogs.13387. [DOI] [PubMed] [Google Scholar]
- 25.Shin J., A Lee J., Oh S., Lee E.H., Choi B.M. Conservative Treatment Without Any Intervention Compared With Other Therapeutic Strategies for Symptomatic Patent Ductus Arteriosus in Extremely Preterm Infants: A Nationwide Cohort Study in Korea. Front. Pediatr. 2021;9:729329. doi: 10.3389/fped.2021.729329. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Ushida T., Moriyama Y., Nakatochi M., Kobayashi Y., Imai K., Nakano-Kobayashi T., Nakamura N., Hayakawa M., Kajiyama H., Kotani T., et al. Antenatal prediction models for short- and medium-term outcomes in preterm infants. Acta Obstet. Gynecol. Scand. 2021;100:1089–1096. doi: 10.1111/aogs.14136. [DOI] [PubMed] [Google Scholar]
- 27.Shin S.H., Kim S.H., Kim Y.-J., Cho H., Kim E.-K., Kim H.-S. The Association of Pregnancy-induced Hypertension with Bronchopulmonary Dysplasia–A Retrospective Study Based on the Korean Neonatal Network database. Sci. Rep. 2020;10:5600. doi: 10.1038/s41598-020-62595-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Shim S.-Y., Cho S.J., Kong K.A., Park E.A. Gestational age-specific sex difference in mortality and morbidities of preterm infants: A nationwide study. Sci. Rep. 2017;7:6161. doi: 10.1038/s41598-017-06490-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Park J.H., Bae J.G., Chang Y.S. Neonatal Outcomes according to the Latent Period from Membrane Rupture to Delivery among Extremely Preterm Infants Exposed to Preterm Premature Rupture of Membrane: A Nationwide Cohort Study. J. Korean Med Sci. 2021;36:e93. doi: 10.3346/jkms.2021.36.e93. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Lee B.K., Lee J.H., Shin J., Jung Y.H., Choi C.W. The association of low body mass index with neonatal morbidities in preterm infants. Sci. Rep. 2021;11:18841. doi: 10.1038/s41598-021-98338-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Marc I., Piedboeuf B., Lacaze-Masmonteil T., Fraser W., Mâsse B., Mohamed I., Qureshi M., Afifi J., Lemyre B., Caouette G., et al. Effect of Maternal Docosahexaenoic Acid Supplementation on Bronchopulmonary Dysplasia-Free Survival in Breastfed Preterm Infants: A Randomized Clinical Trial. JAMA. 2020;324:157–167. doi: 10.1001/jama.2020.8896. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Travers C.P., Carlo W.A., McDonald S.A., Das A., Bell E.F., Ambalavanan N., Jobe A.H., Goldberg R.N., D’Angio C.T., Stoll B.J., et al. Mortality and pulmonary outcomes of extremely preterm infants exposed to antenatal corticosteroids. Am. J. Obstet. Gynecol. 2018;218:130.e1–130.e13. doi: 10.1016/j.ajog.2017.11.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Nakashima T., Inoue H., Sakemi Y., Ochiai M., Yamashita H., Ohga S. Trends in Bronchopulmonary Dysplasia Among Extremely Preterm Infants in Japan, 2003-2016. J. Pediatr. 2021;230:119–125.e7. doi: 10.1016/j.jpeds.2020.11.041. [DOI] [PubMed] [Google Scholar]
- 34.Sloane A.J., Flannery D.D., Lafferty M., Jensen E.A., Dysart K., Cook A., Greenspan J., Aghai Z.H. Hypertensive disorders during pregnancy are associated with reduced severe intraventricular hemorrhage in very-low-birth-weight infants. J. Perinatol. 2019;39:1125–1130. doi: 10.1038/s41372-019-0413-y. [DOI] [PubMed] [Google Scholar]
- 35.Klinger G., Bromiker R., Zaslavsky-Paltiel I., Sokolover N., Lerner-Geva L., Yogev Y., Reichman B. Antepartum Hemorrhage and Outcome of Very Low Birth Weight, Very Preterm Infants: A Population-Based Study. Am. J. Perinatol. 2021;38:1134–1141. doi: 10.1055/s-0040-1710353. [DOI] [PubMed] [Google Scholar]
- 36.Boghossian N.S., Geraci M., Edwards E.M., Horbar J.D. Morbidity and Mortality in Small for Gestational Age Infants at 22 to 29 Weeks’ Gestation. Pediatrics. 2018;141:e20172533. doi: 10.1542/peds.2017-2533. [DOI] [PubMed] [Google Scholar]
- 37.Aldana-Aguirre J.C., Toye J., Shah P.S., Yoon E.W., Kumaran K. Patent ductus arteriosus and small for gestational age infants: Treatment approaches and outcomes. Early Hum. Dev. 2019;131:10–14. doi: 10.1016/j.earlhumdev.2019.02.002. [DOI] [PubMed] [Google Scholar]
- 38.Monier I., Ancel P.-Y., Ego A., Jarreau P.-H., Lebeaux C., Kaminski M., Goffinet F., Zeitlin J. Fetal and neonatal outcomes of preterm infants born before 32 weeks of gestation according to antenatal vs postnatal assessments of restricted growth. Am. J. Obstet. Gynecol. 2017;216:516.e1–516.e10. doi: 10.1016/j.ajog.2017.02.001. [DOI] [PubMed] [Google Scholar]
- 39.Boghossian N.S., Geraci M., Edwards E.M., Horbar J.D. In-Hospital Outcomes in Large for Gestational Age Infants at 22-29 Weeks of Gestation. J. Pediatr. 2018;198:174–180.e13. doi: 10.1016/j.jpeds.2018.02.042. [DOI] [PubMed] [Google Scholar]
- 40.Tarnow-Mordi W., Morris J., Kirby A., Robledo K., Askie L., Brown R., Evans N., Finlayson S., Fogarty M., Gebski V., et al. Delayed versus Immediate Cord Clamping in Preterm Infants. N. Engl. J. Med. 2017;377:2445–2455. doi: 10.1056/NEJMoa1711281. [DOI] [PubMed] [Google Scholar]
- 41.Lodha A., Shah P.S., Soraisham A.S., Rabi Y., Mehrem A.A., Singhal N., for the Canadian Neonatal Network Investigators Association of Deferred vs. Immediate Cord Clamping With Severe Neurological Injury and Survival in Extremely Low-Gestational-Age Neonates. JAMA Netw. Open. 2019;2:e191286. doi: 10.1001/jamanetworkopen.2019.1286. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Shukla V., Elkhateeb O., Shah P.S., Yang J., Lee K.-S. Outcomes of neonates born at <26 weeks gestational age who receive extensive cardiopulmonary resuscitation compared with airway and breathing support. J. Perinatol. 2020;40:481–487. doi: 10.1038/s41372-019-0570-z. [DOI] [PubMed] [Google Scholar]
- 43.Stritzke A., Mohammad K., Shah P.S., Ye X.Y., Bhandari V., Akierman A., Harrison A., Bertelle V., Lodha A. Use and timing of surfactant administration: Impact on neonatal outcomes in extremely low gestational age infants born in Canadian Neonatal Intensive Care Units. J. Matern. Neonatal Med. 2018;31:2862–2869. doi: 10.1080/14767058.2017.1358266. [DOI] [PubMed] [Google Scholar]
- 44.Härtel C., Paul P., Hanke K., Humberg A., Kribs A., Mehler K., Vochem M., Wieg C., Roll C., Herting E., et al. Less invasive surfactant administration and complications of preterm birth. Sci. Rep. 2018;8:8333. doi: 10.1038/s41598-018-26437-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Lodha A., Entz R., Synnes A., Creighton D., Yusuf K., Lapointe A., Yang J., Shah P.S. Early Caffeine Administration and Neurodevelopmental Outcomes in Preterm Infants. Pediatrics. 2019;143:e20181348. doi: 10.1542/peds.2018-1348. [DOI] [PubMed] [Google Scholar]
- 46.Ogawa R., Mori R., Iida K., Uchida Y., Oshiro M., Kageyama M., Kato Y., Tanaka T., Nakata Y., Nishimura Y., et al. Effects of the early administration of sivelestat sodium on bronchopulmonary dysplasia in infants: A retrospective cohort study. Early Hum. Dev. 2017;115:71–76. doi: 10.1016/j.earlhumdev.2017.09.016. [DOI] [PubMed] [Google Scholar]
- 47.Mohamed M.A., El-Dib M., Alqahtani S., Alyami K., Ibrahim A.N., Aly H. Patent ductus arteriosus in premature infants: To treat or not to treat? J. Perinatol. 2017;37:652–657. doi: 10.1038/jp.2017.4. [DOI] [PubMed] [Google Scholar]
- 48.Antoine J., Inglis G.D.T., Way M., O’Rourke P., Davies M.W. Bacterial colonisation of the endotracheal tube in ventilated very preterm neonates: A retrospective cohort study. J. Paediatr. Child Health. 2020;56:1607–1612. doi: 10.1111/jpc.15046. [DOI] [PubMed] [Google Scholar]
- 49.Dicky O., Ehlinger V., Montjaux N., Gremmo-Féger G., Sizun J., Rozé J.C., Arnaud C., Casper C. Policy of feeding very preterm infants with their mother’s own fresh expressed milk was associated with a reduced risk of bronchopulmonary dysplasia. Acta Paediatrica. 2017;106:755–762. doi: 10.1111/apa.13757. [DOI] [PubMed] [Google Scholar]
- 50.Collins C.T., Makrides M., McPhee A.J., Sullivan T.R., Davis P.G., Thio M., Simmer K., Rajadurai V.S., Travadi J., Berry M.J., et al. Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants. N. Engl. J. Med. 2017;376:1245–1255. doi: 10.1056/NEJMoa1611942. [DOI] [PubMed] [Google Scholar]
- 51.Jung Y.H., Park Y., Kim B.I., Choi C.W. Length at birth z-score is inversely associated with an increased risk of bronchopulmonary dysplasia or death in preterm infants born before 32 gestational weeks: A nationwide cohort study. PLoS ONE. 2019;14:e0217739. doi: 10.1371/journal.pone.0217739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52.Jensen C., Ebbesen F., Petersen J., Sellmer A., Bach C., Henriksen T. Hypothermia at neonatal intensive care unit admission was not associated with respiratory disease or death in very preterm infants. Acta Paediatr. 2017;106:1934–1939. doi: 10.1111/apa.13998. [DOI] [PubMed] [Google Scholar]
- 53.Flannery D.D., Dysart K., Cook A., Greenspan J., Aghai Z.H., Jensen E.A. Association between early antibiotic exposure and bronchopulmonary dysplasia or death. J. Perinatol. 2018;38:1227–1234. doi: 10.1038/s41372-018-0146-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54.Ambalavanan N., Van Meurs K.P., Perritt R., A Carlo W., A Ehrenkranz R., Stevenson D.K., A Lemons J., Poole W.K., Higgins R.D. Predictors of death or bronchopulmonary dysplasia in preterm infants with respiratory failure. J. Perinatol. 2008;28:420–426. doi: 10.1038/jp.2008.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Costeloe K.L., Hennessy E.M., Haider S., Stacey F., Marlow N., Draper E.S. Short term outcomes after extreme preterm birth in England: Comparison of two birth cohorts in 1995 and 2006 (the EPICure studies) BMJ. 2012;345:e7976. doi: 10.1136/bmj.e7976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56.Palta M., Gabbert D., Weinstein M.R., Peters M.E., Project N.L. Multivariate assessment of traditional risk factors for chronic lung disease in very low birth weight neonates. The Newborn Lung Project. J. Pediatr. 1991;119:285–292. doi: 10.1016/S0022-3476(05)80746-2. [DOI] [PubMed] [Google Scholar]
- 57.Rojas M.A., Gonzalez A., Bancalari E., Claure N., Poole C., Silva-Neto G. Changing trends in the epidemiology and pathogenesis of neonatal chronic lung disease. J. Pediatr. 1995;126:605–610. doi: 10.1016/S0022-3476(95)70362-4. [DOI] [PubMed] [Google Scholar]
- 58.Bose C., Van Marter L.J., Laughon M., O’Shea T.M., Allred E.N., Karna P., Ehrenkranz R.A., Boggess K., Leviton A. Fetal Growth Restriction and Chronic Lung Disease Among Infants Born Before the 28th Week of Gestation. Pediatrics. 2009;124:e450–e458. doi: 10.1542/peds.2008-3249. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 59.Chida S., Fujiwara T. Stable microbubble test for predicting the risk of respiratory distress syndrome: I. Comparisons with other predictors of fetal lung maturity in amniotic fluid. Eur. J. Pediatr. 1993;152:148–151. doi: 10.1007/BF02072493. [DOI] [PubMed] [Google Scholar]
- 60.Chida S., Fujiwara T., Konishi M., Takahashi H., Sasaki M. Stable microbubble test for predicting the risk of respiratory distress syndrome: II. Prospective evaluation of the test on amniotic fluid and gastric aspirate. Eur. J. Pediatr. 1993;152:152–156. doi: 10.1007/BF02072494. [DOI] [PubMed] [Google Scholar]
- 61.Sweet D.G., Carnielli V., Greisen G., Hallman M., Ozek E., Pas A.T., Plavka R., Roehr C.C., Saugstad O.D., Simeoni U., et al. European Consensus Guidelines on the Management of Respiratory Distress Syndrome–2019 Update. Neonatology. 2019;115:432–450. doi: 10.1159/000499361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 62.De Luca D., Autilio C. Strategies to protect surfactant and enhance its activity. Biomed. J. 2021;44:654–662. doi: 10.1016/j.bj.2021.07.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 63.Stevens T., Blennow M., Soll R. Early surfactant administration with brief ventilation vs selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst. Rev. 2004;3:CD003063. doi: 10.1002/14651858.cd003063.pub2. [DOI] [PubMed] [Google Scholar]
- 64.Aldana-Aguirre J.C., Pinto M., Featherstone R.M., Kumar M. Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: A systematic review and meta-analysis. Pt 1Arch. Dis. Child.-Fetal Neonatal Ed. 2017;102:F17–F23. doi: 10.1136/archdischild-2015-310299. [DOI] [PubMed] [Google Scholar]
- 65.Hodgman J.E. Relationship Between Wilson-Mikity Syndrome and the New Bronchopulmonary Dysplasia. Pediatrics. 2003;112:1414–1415. doi: 10.1542/peds.112.6.1414. [DOI] [PubMed] [Google Scholar]
- 66.Jobe A.H. Mechanisms of Lung Injury and Bronchopulmonary Dysplasia. Am. J. Perinatol. 2016;33:1076–1078. doi: 10.1055/s-0036-1586107. [DOI] [PubMed] [Google Scholar]
- 67.Watterberg K.L., Demers L.M., Scott S.M., Murphy S. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics. 1996;97:210–215. doi: 10.1542/peds.97.2.210. [DOI] [PubMed] [Google Scholar]
- 68.Licini C., Tossetta G., Avellini C., Ciarmela P., Lorenzi T., Toti P., Gesuita R., Voltolini C., Petraglia F., Castellucci M., et al. Analysis of cell-cell junctions in human amnion and chorionic plate affected by chorioamnionitis. Histol. Histopathol. 2016;31:759–767. doi: 10.14670/HH-11-719. [DOI] [PubMed] [Google Scholar]
- 69.Palmsten K., Nelson K.K., Laurent L.C., Park S., Chambers C.D., Parast M.M. Subclinical and clinical chorioamnionitis, fetal vasculitis, and risk for preterm birth: A cohort study. Placenta. 2018;67:54–60. doi: 10.1016/j.placenta.2018.06.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 70.Tita A.T., Andrews W.W. Diagnosis and Management of Clinical Chorioamnionitis. Clin. Perinatol. 2010;37:339–354. doi: 10.1016/j.clp.2010.02.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 71.Suzuki S. Association between clinical chorioamnionitis and histological funisitis at term. J. Neonatal-Perinatal Med. 2019;12:37–40. doi: 10.3233/NPM-17155. [DOI] [PubMed] [Google Scholar]
- 72.Abu-Shaweesh J.M., Almidani E. PDA: Does it matter? Int. J. Pediatr. Adolesc. Med. 2020;7:9–12. doi: 10.1016/j.ijpam.2019.12.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 73.Hundscheid T., Onland W., Kooi E.M., Vijlbrief D.C., de Vries W.B., Dijkman K.P., van Kaam A.H., Villamor E., Kroon A.A., Visser R., et al. Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus. N. Engl. J. Med. 2022 doi: 10.1056/NEJMoa2207418. [DOI] [PubMed] [Google Scholar]
- 74.Chen X., Qiu X., Sun P., Lin Y., Huang Z., Yang C., Walther F.J. Neonatal ibuprofen exposure and bronchopulmonary dysplasia in extremely premature infants. J. Perinatol. 2020;40:124–129. doi: 10.1038/s41372-019-0444-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
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