Educational Aims
The reader will come to appreciate:
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Many adults who were born extremely preterm in the 1980s and 1990s, and who did not develop bronchopulmonary dysplasia, have lung function in the low normal range.
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Extremely preterm born infants with a history of bronchopulmonary dysplasia may be at increased risk of a chronic obstructive pulmonary disease in middle age and older years based on the trajectory of their lung function.
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Despite improved neonatal care and the advent of surfactant therapy, the rate of bronchopulmonary dysplasia has not decreased.
Abstract
Extreme preterm (EP) birth, denoting delivery before the onset of the third trimester, interrupts intrauterine development and causes significant early-life pulmonary trauma, thereby posing a lifelong risk to respiratory health. We conducted a systematic review and meta -analysis to investigate adult lung function following EP birth (gestational age <28 weeks); comparing forced expiratory volume in first second (FEV 1 ), forced vital capacity (FVC), and FEV 1 /FVC to reference values. Subgroup differences were explored based on timing of birth relative to surfactant use (1991) and bronchopulmonary dysplasia (BPD) status. Systematic searches were performed in Medline, EMBASE, Web of Science and Cochrane Central. Quality assessments were carried out using a modified Newcastle-Ottawa Scale for cohort studies. Sixteen studies encompassing 1036 EP-born adults were included, with 14 studies (n = 787) reporting data as %predicted, and 11 (n = 879) as z-score (not mutually exclusive). Overall mean [95 % confidence interval (CI)] %FEV 1 was 85.30 (82.51; 88.09), %FVC was 94.33 (91.74; 96.91), and FEV 1 /FVC was 79.54 (77.71 to 81.38), all three with high heterogeneity. Overall mean (95 %CI) zFEV 1 was −1.05 (-1.21; −0.90) and zFVC was.
−0.45 (-0.59; −0.31), both with moderate heterogeneity. Subgroup analyses revealed no difference in FEV 1 before versus after widespread use of surfactant, but more impairments after neonatal BPD. This meta -analysis revealed significant airflow limitation in EP-born adults, mostly explained by those with neonatal BPD. FEV 1 was more reduced than FVC, and FEV 1 /FVC was at the lower limit of normal. Although at a group level, most adult EP-born individuals do not meet COPD criteria, these findings are concerning.
Introduction
Significant advancements in perinatal care during the 1980s and 1990 led to improved survival of infants born at the limit of viability, with changes including technological innovations and refinements, as well as medical breakthroughs including administering antenatal steroids to the mothers and exogenous surfactant to the newborn . Preterm birth may adversely impact future lung function for several reasons, including unfavorable antenatal factors that led to the early delivery, interrupted intra-uterine lung development which must proceed in an extra-uterine environment, and lifesaving but also harmful intensive care treatment Bronchopulmonary dysplasia (BPD) is a chronic lung disease developing in 50–60 % of infants born EP. BPD is characterized by interrupted and dysregulated lung development and is currently defined by prolonged need for oxygen supplementation . Improved survival of immature newborns has not been paralleled by a decrease in the rate of neonatal BPD .
Development of the respiratory system commences early in fetal life and has not been finalized at birth . Lung function normally increases through childhood and adolescence until early adulthood where it reaches a maximum and then gradually declines with aging . The expected life-long lung function trajectories for EP-born cannot yet be fully described, as their high survival rates are recent achievements . Studies indicate that they fail to reach their expected peak in early adulthood , a scenario associated with early onset chronic obstructive pulmonary disease (COPD) in studies of general populations . Extremely preterm (EP) born infants (before 28 weeks pregnancy) currently constitute almost one in 200 children growing up in high-income countries . EP birth places significant demands on the health care services extending far beyond the neonatal period, and solid evidence on their future health prospects therefore needs to be established .
We have conducted a systematic review and meta -analysis to assess lung function in adults born EP, using forced expiratory volume in first second (FEV 1 ), forced vital capacity (FVC), and FEV 1 /FVC as outcomes, comparing results with established reference values.
Methods
The review protocol was registered in PROSPERO in November 2020 (CRD42020212242), and the reporting follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.
Eligibility criteria
Cross-sectional, longitudinal, case-control, and cohort studies, with and without control subjects, reporting pre-bronchodilator spirometry data (FEV 1 , FVC) in adults born EP (gestational age (GA) <28 weeks or birthweight (BW) <1000 g) were eligible for inclusion. Adults were defined as age ≥18 years. These age and GA/BW cut-offs were applied to the reported mean values of the studies that were assessed for eligibility. Studies with FEV 1 or FVC not expressed as %predicted or z-scores were excluded. Participants were included irrespective of BPD status. No language restrictions were applied. Surfactant was considered introduced to larger numbers of EP-born infants from 1990 to 91, e.g. the Osiris®-trial .
Information sources
The search was performed in collaboration with a librarian at the Medical Faculty at the University of Bergen. We searched the following databases: Medline, Embase, Web of Science and the Cochrane Library. To identify relevant literature that might have escaped the search, we also screened reference lists of the included studies and relevant reviews.
Search strategy and selection
The initial search started on October 15th and ended on October 19th, 2020. It was updated on March 21st, 2022. Keywords and medical subject headings (MeSH) terms used were “Respiratory function OR lung function OR spirometry OR forced expiratory volume in one second OR forced vital capacity OR FEV 1 OR FVC”, combined with “Preterm OR low birth weight OR bronchopulmonary dysplasia OR BPD”, combined with “Adult” (online data supplement).
After retrieving the studies, they were imported to EndNote X9. One reviewer (HLL) removed duplicates, and two reviewers (MV and TH) independently screened titles and abstracts (if available) for eligibility, according to inclusion and exclusion criteria. Subsequently, full texts were retrieved and independently assessed for eligibility by the same two reviewers, blinded to each other’s decisions. In cases of disagreement, a third investigator (MSE) was consulted, and disagreements were solved by consensus. Decisions were recorded in an Excel spreadsheet. Multiple studies had participants from the same cohorts. To avoid reporting duplicated spirometry values from the same individuals, we included the study with the highest number of participants. One author was contacted on this issue for clarification .
Data collection process
A data extraction form was made in an Excel spreadsheet, and the data were extracted (HLL) and controlled (MV). In case of dissent, a third investigator (MSE) was consulted, disagreements were solved by consensus. In case of missing or non-extractable data, e.g., when results from very preterm-born and EP-born were reported combined, authors were contacted for additional information. Two authors replied by mail, and this led to one study being excluded as the mean GA of the participants was > 28 weeks.
Quality assessment of individual studies
Two reviewers (MV and MSE) independently assessed the methodological quality of the individual studies by applying a modified version of the Newcastle Ottawa Scale (NOS) for cohort studies (online data supplement). Within the selection domain, each study was assessed and scored for the representativeness of the exposed cohort (truly/somewhat representative for the average EP/ELBW born adult ≥18 years of age in the community), and ascertainment of the exposure (EP/ELBW-birth; i.e. medical records) (maximum of two points). In the outcome domain, one point was given for assessment of outcomes if spirometry was performed according to American Thoracic Society (ATS)/European Respiratory Society (ERS)-criteria , and one point was assigned for adequacy of follow-up if ≥80 % of subjects were followed and/or the study provided descriptions of those lost to follow-up. Thus, individual studies could achieve a maximum possible score of four points. Disagreements between the reviewers were solved by consensus or through consulting a third author (TH).
Data synthesis and analysis
The meta -analyses were conducted using the “meta” package in the R statistical environment. The mean of outcomes and 95 % confidence intervals (CI) are reported as the overall synthesized measure of effect size for expiratory airflow outcomes for adults born extremely premature. Only individual studies reporting comparable outcomes that could be (re)expressed as a mean and 95 % CI were included in the meta -analyses. Studies reporting outcomes both as %predicted and z-values were included in both analyses. Further, eligible cohorts in studies reporting outcomes from several cohorts were entered into the analyses as separate cohorts. Thus, number of studies and participants in the various categories do not add up to the reported total.
As considerable heterogeneity was expected between studies, pooled mean effect size was calculated using the random effects model using a Restricted maximum-likelihood estimator (REML). An I 2 statistic was computed as an indicator of heterogeneity in percentages. Increasing values show increasing heterogeneity, with values of 0 % indicating no heterogeneity, 50 % indicating moderate heterogeneity, and 75 % indicating high heterogeneity . Subgroup analyses were performed by BPD-status and by birth before (before 1991) vs. after (from 1991 and onwards) widespread use of surfactant treatment . Cut-off had to be set at a year because surfactant use in the early 1990s was incomplete at most institutions and reporting was somewhat inconsistent. However, splitting in 1991 fitted well with what was reported in most studies. Publication bias was investigated using a funnel plot and Egger’s regression test to assess funnel plot asymmetry (alpha level = 0.1) .
Results
Study selection
The first systematic search identified 3175 references from the four databases and one from other sources; 146 were assessed as full text articles, and this yielded 15 studies ( Fig. 1 ). The updated systematic search in 2022 identified 208 studies from the same four databases, where three additional studies met the inclusion criteria. However, due to reporting of the same participants, one of the three studies were excluded, whereas one replaced a study from the first search. In total, we ended up with 16 included studies.
Study characteristics
All 16 studies were conducted between 2003 and 2022, with participants born EP between 1977 and 2000. Generally, the studies were similar with respect to their observational design and the outcome measurement methods, but diverse with respect to the recruitment procedures, the number of participants, and the choice of reference equations for spirometry measurements. Characteristics of studies and a summary of findings from included studies are described in Table 1 .
| Author, Year, Title | Study Design | Aim of the Study | Study Group | Spirometry | Results | Definition BPD |
|---|---|---|---|---|---|---|
| Bårdsen, 2022 “Tracking of lung function from 10 to 35 years after being born extremely premterm or with extremely low birth weight” | Population based, longitudinal study | To describe lung function trajectories from 10 to 35 years of age for individuals born extremely preterm, and address potential cohort effects over a period that encompassed major changes in perinatal care. | Cohort 82 – 85 N = 45 GA = 27.3 (23–32) BW = 1012 (580–1480) BPD = 12 Antenatal steroids = 16 Postnatal steroids = 4 Asthma = 13 Maternal smoking = 22 Age at testing = 24.7 yr ± 1.2 Cohort 91 – 92 N = 31 GA = 26.9wk (23–31) BW = 933 g (570–1400) BPD = 12 Antenatal steroids = 15 Surfactant = 17 Postnatal steroids = 10 Asthma = 12 Maternal smoking = 13 Age at testing = 17.7 yr ± 0.36 Cohort 99 – 00 N = 50 GA = 26.8wk ± 1.6 BW = 850 g ± 175 BPD = 23 Antenatal steroids = 46 Surfactant = 49 Postnatal steroids = 18 Asthma = 8 Maternal smoking = 13 Age at testing = 19.8 yr ± 0.7 | The American Thoracic Society and European Respiratory Society guidelines. Global Lung Initiative | Cohort 82 – 85 FEV 1 = 87.9 ± 16.5 FVC = 95.3 ± 17.5 FEV 1 /FVC = 78.6 ± 7.3 BPD (n = 12) FEV 1 = 84.1 ± 11.7 FVC = 92.4 ± 14.6 zFEV 1 = -1.3 ± 1.0 zFVC = -0.6 ± 1.2 non-BPD (n = 33) FEV 1 = 89.3 ± 17.9 FVC = 96.3 ± 18.5 zFEV 1 = -0.9 ± 1.5 zFVC = -0.4 ± 1.6 Cohort 91 – 92 FEV 1 = 88.8 ± 10.3 FVC = 95.8 ± 10.3 FEV 1 /FVC = 81.7 ± 10.0 BPD (n = 12) FEV 1 = 82.9 ± 8.8 FVC = 97.3 ± 6.2 zFEV 1 = -1.5 ± 0.7 zFVC = -0.2 ± 0.5 non-BPD (n = 19) FEV 1 = 92.6 ± 9.6 FVC = 94.9 ± 12.3 zFEV 1 = -0.6 ± 0.8 zFVC = -0.4 ± 1.0 Cohort 99 – 00 FEV 1 = 92.4 ± 12.1 FVC = 97.5 ± 12.4 FEV 1 /FVC = 82.4 ± 7.8 BPD (n = 23) FEV 1 = 91.6 ± 12.1 FVC = 95.6 ± 13.5 zFEV 1 = -0.7 ± 1.0 zFVC = -0.4 ± 1.1 non-BPD (n = 27) FEV 1 = 93.2 ± 12.3 FVC = 99.1 ± 11.3 zFEV 1 = -0.6 ± 1.1 zFVC = -0.1 ± 0.9 | BPD defined as need for supplemental oxygen or respiratory support at a postmenstrual age of 36 weeks. |
| Doyle, 2003 “Adverse Effects of Smoking on Respiratory Function in Young Adults Born Weighing Less Than 1000 Grams” | Population based, longitudinal study | “To determine whether active smoking has an adverse impact on respiratory function of young adults of extremely low birth weight” | All participants: N = 44 (males 16, females 28) GA = 27.4wk ± 2.0 BW = 876 g ± 85 BPD = 18 (40.9 %) Maternal smoking = 7 (15.9 %) Age at testing = 20.2 yr ± 1.0 Non-smokers: N = 30 (males 9, females 21) GA = 27.2wk ± 1.9 BW = 872 g ± 90 BPD = 13 (43 %) Asthma = 3 (10 %) Maternal smoking = 4 (13 %) Smokers: N = 14 (males 7, females 7) GA = 27.9 ± 2.2 BW = 884 g ± 74 BPD = 5 (36 %) Asthma = 6 (43 %) Maternal smoking = 3 (21 %) The subjects were born at Royal Women’s Hospital, Melbourne, Australia, during 1977–1980. Out of the 60 consecutive ELBW survivors, 44 subjects did measure respiratory function. | Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault J-C. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J. 1993;6(suppl 16):5–40 | Non-smokers: FEV 1 = 93.0 ± 15.6 FVC = 99.9 ± 15.1 FEV 1 /FVC = 81.2 ± 12.1 FEF 25-75% = 75.5 ± 24.9 Smokers: FEV 1 = 85.8 ± 18.7 FVC = 104.0 ± 13.6 FEV 1 /FVC = 70.9 ± 10.7 FEF 25-75% = 53.1 ± 21.4 | Clinical signs of respiratory distress with an abnormal chest radiograph and an oxygen requirement after 28 days of age. |
| Doyle, 2017 “Increasing airway obstruction from 8 to 18 years in extremely preterm/low-birthweight survivors born in the surfactant era” | Population based, longitudinal study | “To (1) compare airflow at 8 and 18 years and changes between 8 and 18 years of EP/ELBW survivors with normal birth weight controls, and (2) within the EP/ELBW group, to determine the associations of BPD in the newborn period, and of active smoking in adolescence with airflow” | Preterm: N = 297 (males 137, females 160) GA = 26.7wk ± 1.9 BW = 888 g ± 161 Antenatal steroids = 216 (73 %) Surfactant = 119 (40 %) Postnatal steroids = 97 (33 %) BPD = 121 (41 %) Asthma = 40 (21 %) Smokers = 35 (17 %) Assisted ventilation = 281 (95 %) Age at testing = 17.9 yr ± 0.9 Controls: N = 260 (males 126, females 135) GA = 39.2wk ± 1.4 BW = 3386 g ± 438 Antenatal steroids = 3 (1 %) Asthma = 27 (19 %) Smokers = 21 (13 %) Age at testing = 18.0 yr ± 0.8 The subjects were derived from a preterm cohort of all survivors born EP or ELBW in the state of Victoria, Australia in 1991–1992. Out of the 297 subjects who survived, 209 (70 %) completed the lung function test at 18 years of age. | The American Thoracic Society and European Respiratory Society guidelines. Global Lung Initiative | Preterm (n = 209) FEV1 = 87.9 ± 12.9 FVC = 94.4 ± 12.1 FEV1/FVC = 81.5 ± 9.5 FEF25-75 % = 73.1 ± 22.9 zFEV 1 = -1.03 ± 1.08 zFVC = -0.48 ± 1.03 zFEV 1 /FVC = -0.85 ± 1.25 zFEF 25-75% = −1.37 ± 1.19 Controls (n = 154) FEV1 = 98.7 ± 10.7 FVC = 99.0 ± 10.4 FEV1/FVC = 87.0 ± 6.3 FEF25-75 % = 95.9 ± 21.4 zFEV 1 = -0.10 ± 1.03 zFVC = -0.09 ± 0.87 zFEV 1 /FVC = -0.06 ± 0.97 zFEF 25-75% = −0.23 ± 0.98 BPD (n = 77) FEV 1 = 82.7 ± 13.7 FVC = 92.1 ± 13.3 FEV 1 /FVC = 78.6 ± 10.6 FEF 25-75% = 65.3 ± 22.6 zFEV 1 = -1.46 ± 1.14 zFVC = -0.68 ± 1.14 zFEV 1 /FVC = -1.17 ± 1.35 zFEF 25-75% = −1.79 ± 1.23 Non-BPD (n = 132) FEV 1 = 90.9 ± 11.4 FVC = 95.8 ± 11.2 FEV 1 /FVC = 83.3 ± 8.4 FEF 25-75% = 77.7 ± 21.9 zFEV 1 = -0.77 ± 0.96 zFVC = -0.36 ± 0.95 zFEV 1 /FVC = -0.67 ± 1.15 zFEF 25-75% = −1.12 ± 1.10 | BPD defined as oxygen or ventilator dependency at 36 weeks’ postmenstrual age, consistent with moderate or severe BPD according to the subsequent National Heart, Lung and Blood Institute-sponsored workshop definition. |
| Duke, 2018 “Premature birth affects the degree of airway dysanapsis and mechanical ventilatory constraints” | Center based, cross-sectional study | “Whether or not the infants born preterm and those with BPD had smaller airways, indexed via the dysanapsis ratio, than those born at term” | BPD N = 21 (males 11, females 10) GA = 27.6wk ± 2.1 (range 24.5–31) BW = 1040 g ± 240 (range 740–1420) Age at testing = 23.1 yr ± 4.1 Non-BPD N = 14 (males 8, females 6) GA = 28.0wk ± 2.0 (range 25–32) BW = 1060 g ± 320 (range 650–1760) Age at testing = 21.1 yr ± 2.6 Controls N = 34 (males 19, females 15) Age at testing = 22.5 yr ± 3.5 A total of 166 non-smoking individuals aged 18–32 years volunteered for the study. Unknown how many who was invited. Of the 166 individuals, 97 did not qualify or were excluded for various reasons. 69 (41.6 %) individuals were included. | The American Thoracic Society and European Respiratory Society guidelines. Global Lung Initiative | BPD FEV 1 = 72.0 ± 19.0 FVC = 92.0 ± 16.0 FEV 1 /FVC = (%) 76.0 ± 11.0 FEF 25-75% = 46.0 ± 18.0 FEV 1 (L) = 3.0 ± 1.1 FVC (L) = 4.5 ± 1.4 FEV 1 /FVC = (%) 65.0 ± 9.0 FEF 25-75% =2.1 ± 0.9 Non-BPD FEV 1 = 91.0 ± 14.0 FVC = 99.0 ± 10.0 FEV 1 /FVC (%) = 90.0 ± 8.0 FEF 25-75% = 74.0 ± 22.0 FEV 1 (L) = 3.5 ± 0.9 FVC (L) = 4.5 ± 1.0 FEV 1 /FVC (%) = 79.0 ± 8.0 FEF 25-75% = 3.2 ± 1.1 Controls FEV 1 = 104 ± 9 FVC = 103 ± 9 FEV 1 /FVC (%) = 100 ± 5 FEF 25-75% = 103 ± 17 FEV 1 (L) = 4.2 ± 0.8 FVC (L) = 4.9 ± 1.0 FEV 1 /FVC (%) = 86 ± 4 FEF 25-75% = 4.6 ± 1.0 | Defined BPD as requirement for supplemental oxygen > 28 postnatal days and radiographic changes and severity according to oxygen requirements at 36 weeks postmenstrual age. |
| Duke, 2019 “Alleviating mechanical constraints to ventilation with heliox improves exercise endurance in adult survivors of very preterm birth” | Center based, cross-sectional study | “To test whether expiratory flow limitation (EFL), during exercise negatively affects exercise endurance in preterm subjects” | Preterm: N = 17 (males 8, females 9) GA = 27.9wk ± 1.9 (Range 24–32) BW = 1150 g ± 410 Age at testing = 21.0 yr ± 2.0 Controls: N = 16 (males 7, females 9) Age at testing = 22.0 yr ± 2.0 33 participants provided written informed consent prior to participation. Not stated how many that were asked but refers to Lovering et. Al. 2013. | ATS/ERS. Global Lung Initiative | Preterm FEV 1 = 86.0 ± 17.0 FVC = 94.0 ± 11.0 FEV 1 /FVC = 90.0 ± 12.0 FEF 25-75% = 71.0 ± 26.0 FEV 1 (L) = 3.4 ± 1.0 FVC (L) = 4.3 ± 1.2 FEV 1 /FVC = 78 ± 11 FEF 25-75% = 3.1 ± 1.3 Controls FEV 1 = 100 ± 7 FVC = 100 ± 6 FEV 1 /FVC (%) = 99 ± 5 FEF 25-75% = 101 ± 25 FEV 1 (L) = 4.0 ± 1.0 FVC (L) = 4.7 ± 1.2 FEV 1 /FVC (%) = 86 ± 5 FEF 25-75% = 4.4 ± 1.4 | BPD defined as requirement for supplemental oxygen > 28 postnatal days and radiographic changes and severity according to oxygen requirements at 36 weeks postmenstrual age. |
| Flahault, 2020 “Duration of neonatal oxygen supplementation, erythropoiesis and blood pressure in young adults born preterm” | Center based, cross-sectional study | “To evaluate haemoglobin and erythropoietin levels in young adults born preterm, to identify neonatal events associated with erythropoiesis in adulthood and to examine the relationship of haemoglobin levels with respiratory function and blood pressure” | Preterm N = 101 (males 45, females 56) GA = 27.1wk ± 1.4 BW = 965 g ± 230 Antenatal steroids = 41 (41 %) Surfactant = 46 (48 %) Smokers = 23 (23 %) BPD = 66 Non-BPD = 33 Age at testing = 23.2 yr ± 2.2 Controls: N = 105 (males 43, females 62) GA = 39.6wk ± 1.1 BW = 3421 g ± 387 Smokers = 20 (19 %) Age at testing = 23.2 yr ± 2.5 A cohort of 101 young adults who had been born premature between 1987 and 1997. The data were obtained from the Health of Adults born Preterm Investigation (HAPI) project, in Montreal, Canada. | American Thoracic Society/European Respiratory Society guidelines. Global Lung Initiative | Preterm (n = 99) FEV 1 = 89.1 ± 12.7 FVC = 98.6 ± 11.4 zFEV 1 = -0.915 ± 1.071 zFVC = -0.12 ± 0.956 zFEV 1 /FVC = -1.15 ± 1.07 FEV 1 (L) = 3.25 ± 0.74 FVC (L) = 4.2 ± 1.0 FEV 1 /FVC = 0.78 ± 0.09 Controls FEV 1 = 100.0 ± 10.8 FVC = 103.4 ± 10.9 zFEV 1 = 0.012 ± 0.926 zFVC = 0.28 ± 0.899 zFEV 1 /FVC = -0.44 ± 0.9 FEV 1 (L) = 3.89 ± 0.79 FVC (L) = 4.7 ± 1.0 FEV 1 /FVC = 0.831 ± 0.066 BPD FEV 1 = 87.4 ± 12.4 FVC = 97.3 ± 11.8 zFEV 1 = -1.061 ± 1.047 zFVC = -0.227 ± 0.993 zFEV 1 /FVC = -1.216 ± 1.043 FEV 1 (L) = 3.24 ± 0.73 FVC (L) = 4.2 ± 1.0 FEV 1 /FVC = 0.774 ± 0.087 Non-BPD FEV 1 = 93.6 ± 12.3 FVC = 101.4 ± 10.6 zFEV 1 = -0.532 ± 1.039 zFVC = 0.112 ± 0.879 zFEV 1 /FVC = -0.911 ± 1.095 FEV 1 (L) = 3.29 ± 0.78 FVC (L) = 4.2 ± 1.1 FEV 1 /FVC = 0.799 ± 0.094 | Not stated. |
| Gibson, 2015 “Lung Function in Adult Survivors of Very Low Birth Weight, With and Without Bronchopulmonary Dysplasia” | Population based, longitudinal study | “To report lung function data in adulthood of VLBW survivors compared with normal birth weight controls, and in those who had BPD compared with those without BPD” | ELBW with Spirometry N = 47 (males 17, females 30) GA = 27.5wk ± 1.9 BW = 871 g ± 90 BPD = 19 (40.4 %) Asthma = 17 (36 %) Smokers = 16 (34 %) Age at testing = 26.3 yr ± 1.1 VLBW with Spirometry N = 40 (males 21, females 19) GA = 29.5wk ± 1.5 BW = 1227 g ± 139 BPD = 5 (12.5 %) Asthma = 10 (25 %) Smokers = 12 (32 %) Age at testing = 25.4 yr ± 0.5 Controls with Spirometry: N = 20 (males 12, females 8) GA = 40.2wk ± 0.8 BW = 3542 g ± 451 Asthma = 6 (30 %) Smokers = 5 (25 %) Age at testing = 24.9 yr ± 0.2 Participants born between 1977 and 1982 at the Royal Women’s Hospital in Melbourne, Australia. Derived from three groups: (1) 86 consecutive survivors of ELBW, born 1977–1982, where 47 did lung function test. (2) 124 consecutive survivors of VLBW, born 1980–1982 (3) 60 randomly selected controls of normal birth weight, born in the last 6 months of recruitment to the study. | Lung function was measured according to the American Thoracic Society (ATS) and European Respiratory Socity (ERS) guidelines. Global Lung Initiative | ELBW zFEV 1 = -0.77 ± 1.39 zFVC = -0.25 ± 1.01 zFEV 1 /FVC = -0.79 ± 1.33 zFEF 25-75% = −1.13 ± 1.40 VLBW zFEV 1 = -0.63 ± 1.69 zFVC = -0.13 ± 1.17 zFEV 1 /FVC = -0.77 ± 1.51 zFEF 25-75% = −1.05 ± 1.84 Control zFEV 1 = 0.38 ± 0.79 zFVC = 0.29 ± 0.75 zFEV 1 /FVC = -0.003 ± 0.75 zFEF 25-75% = 0.09 ± 0.97 BPD (n = 24) zFEV 1 = -1.37 ± 2.21 zFVC = -0.60 ± 1.34 zFEV 1 /FVC = -0.94 ± 1.42 zFEF 25-75% = −1.54 ± 2.16 Non-BPD (n = 63) zFEV 1 = -0.47 ± 1.30 zFVC = -0.10 ± 1.16 zFEV 1 /FVC = -0.45 ± 1.28 zFEF 25-75% = −0.72 ± 1.46 | Respiratory distress and oxygen dependency beyond 28 days with classical chest X-ray changes of Stage 3 or 4 BPD beyond 28 days of age. |
| Gough, 2014 «Impaired lung function and health status in adult survivors of bronchopulmonary dysplasia” | Population based, cross-sectional study | “To report respiratory symptoms, lung function and health-related quality of life (HRQoL) in adult BPD survivors compared with preterm (non-BPD) and full-term controls” | BPD N = 56 (males 31, females 25) GA = 27.1wk ± 2.1wk BW = 939 g ± 246 g Antenatal steroids = 16 (29 %) Surfactant = 18 (32 %) Postnatal steroids = 19 (34 %) Smokers = 11 (18 %) Maternal smoking = 11 (25 %) Age at testing = 24.1 yr ± 4.0 Non-BPD N = 40 (males 15, females 25) GA = 31.2wk ± 2.3 BW = 1234 g ± 223 Antenatal steroids = 13 (33 %) Smokers = 8 (18 %) Maternal smoking = 8 (29 %) Age at testing = 25.3 yr ± 4.0 Controls N = 55 (males 27, females 28) GA = 39.8wk ± 1.2 BW = 3556 g ± 429 Smokers = 15 (24 %) Age at testing = 25.8 yr ± 3.9 Individuals were identified from hospital records at the Royal Maternity Hospital, Belfast, UK, and traced through the Business Services Organisation (BSO) via their general practitioner. The study population comprised 129 preterm adult, were 72 had BPD, 57 preterm without BPD, and 78 full-term controls. Lung function was completed by 56 subjects with BPD, 40 without BPD and 55 full-term controls. | European Respiratory Society guidelines. Quanjer PH, Tammeling GJ, Cotes JE, et al. Lung volumes and forced ventilatory flows. Eur Respir J 1993; 6: Suppl. 16, 5–40. | BPD : FEV1 81.89 ± 15.90 FVC 90.11 ± 14.46 FEV1/FVC (%) 94.32 ± 13.41 FEF25-75 61.63 ± 23.59 zFEV1 = -1.41 ± 1.25 zFVC = -0.79 ± 1.14 zFEV1/FVC = -0.68 ± 0.22 zFEF 23-75% = −1.80 ± 1.10 Non-BPD : FEV1 96.98 ± 15.22 FVC 101.85 ± 12.60 FEV1/FVC (%) 98.45 ± 10.32 FEF25-75 74.93 ± 22.06 zFEV1 = -0.19 ± 1.16 zFVC = 0.17 ± 0.98 zFEV1/FVC = -0.13 ± 1.22 zFEF 25-75% = −1.13 ± 1.02 Controls: FEV1 101.16 ± 11.40 FVC 101.67 ± 10.83 FEV1/FVC (%) 102.67 ± 7.18 FEF25-75 90.96 ± 21.55 zFEV 1 = 0.14 ± 0.96 zFVC = 0.12 ± 0.94 zFEV 1 /FVC = 0.34 ± 0.89 zFEF 25-75% = −0.56 ± 1.45 | BPD defined as requirement for supplemental oxygen at 28 post-natal days and radiographic changes. Severity (mild, moderate or severe) graded according to oxygen requirements at 36 weeks post-menstrual age |
| Harris, 2020 “Lung function and exercise capacity in prematurely born young people” | Population based, longitudinal study | “To determine if lung function abnormalities in young people born very prematurely routinely exposed to antenatal corticosteroids and postnatal surfactant were associated with reduced exercise capacity” | Premature N = 126 (males 63, females 63) GA = 26.9wk ± 1.4 BW = 899 g ± 220 Surfactant = 122 (97 %) Systemic steroids given prior to extubation = 33 (26 %) Asthma = 11 (9 %) Smokers = 15 (12 %) Maternal smoking = 25 (21 %) Age at testing = 17.9 yr ± 0.8 Participants were derived from the United Kingdom Oscillation Study (UKOS), which was a randomized trial of 797 infants born very premature at less than 29 weeks of gestational age. 126 subjects gave informed, written consent to take part in the study. | ATS/ERS Standards. Global Lung Initiative | Premature zFEV 1 = -1.0 ± 1.3 zFVC = -0.3 ± 1.4 zFEV 1 /FVC = -1.1 ± 1.2 zFEF 25-75% = −1.5 ± 1.3 | Having an oxygen requirement at 36 weeks corrected gestational age |
| Hurst, 2020 “Respiratory and Cardiovascular Outcomes in survivors of Preterm Birth at 19 years” | Population based, longitudinal study | “To assess the trajectory of respiratory and cardiovascular outcomes at transition to adulthood in a national longitudinal cohort study of births before 26 weeks of gestation in the UK and Eire” | Extreme premature N = 129 (males 61, females 68) GA = 24.9wk ± 0.7 BW = 741 g ± 121 Postnatal steroids = 98 (76 %) Asthma = 30 (29.1 %) Age at testing = 19 yr Participants born in the UK between March and December 1995. Out of the 307 subjects from the original EPICure study cohort, 129 subjects consented on continuation of the study and 65 controls. | ATS/ERS guidelines Global Lung Initiative | Pre-bronchodilator All EP zFEV 1 = -1.61 ± 1.17 (-5.06 to 0.68) zFVC = -0.76 ± 1.06 (-4.45 to 1.59) zFEV 1 /FVC = -1.33 ± 1.24 (-3.95 to 2.28) zFEF 25-75% = −1.86 ± 1.22 (-5.21 to 1.75) FEV 1 (L) = 2.87 ± 0.72 (1.29 to 4.66) FVC (L) = 3.71 ± 0.89 (1.31 to 6.09) FEV 1 /FVC = 0.78 ± 0.10 (0.52 to 1.00) FEF 25-75% (L) = 2.62 ± 1.03 (0.58 to 6.71) EP with BPD (n = 87) zFEV 1 = -1.83 ± 1.17 (-5.06 to 0.68) zFVC = -0.84 ± 1.07 (-4.45 to 1.59) zFEV 1 /FVC = -1.57 ± 1.21 (-3.95 to 2.28) zFEF 25-75% = −2.14 ± 1.19 (-5.21 to 1.75) FEV 1 (L) = 2.77 ± 0.69 (1.29 to 4.35) FVC (L) = 3.68 ± 0.87 (3.68 to 0.87) FEV 1 /FVC (%) = 0.76 ± 0.10 (0.52 to 1.00) FEF 25-75% (L) = 2.41 ± 0.97 (0.58 to 6.71) EP no BPD (n = 36) zFEV 1 = -1.05 ± 0.99 (-3.87 to 0.26) zFVC = -0.59 ± 1.02 (-2.84 to 0.87) zFEV 1 /FVC = -0.75 ± 1.14 (-2.62 to 2.18) zFEF 25-75% = −1.17 ± 1.02 (-3.66 to 0.91) FEV 1 (L) = 3.10 ± 0.73 (1.56 to 4.66) FVC (L) = 3.79 ± 0.93 (2.20 to 6.09) FEV 1 /FVC (%) = 0.82 ± 0.08 (0.65 to 1.00) FEF 25-75% (L) = 3.14 ± 0.98 (1.18 to 6.01) Controls zFEV 1 = -0.29 ± 0.89 (-2.24 to 1.92) zFVC = -0.00 ± 0.93 (-2.24 to 1.82) zFEV 1 /FVC = -0.42 ± 1.13 (-3.06 to 2.21) zFEF 25-75% = −0.44 ± 1.11 (-2.64 to 2.08) FEV 1 (L) = 3.56 ± 0.65 (2.30 to 5.29) FVC (L) = 4.25 ± 0.87 (2.35 to 6.09) FEV 1 /FVC (%) = 0.85 ± 0.08 (0.60 to 0.99) FEF 25-75% (L) = 3.88 ± 1.09 (1.56 to 6.95) | Chronic oxygen-dependent lung disease persisting beyond 36 weeks post menstrual age. |
| Landry, 2016 “Lung Function and Bronchial Hyperresponsiveness in Adults Born Prematurely: A Cohort Study” | Population based, cross-sectional study | “To describe the quality of life, pulmonary lung function, bronchial hyperresponsiveness, body composition and trends in physical activity of adults born prematurely, with or without respiratory complications” | BPD N = 31 (males 11, females 20) GA = 27.4 wk ± 2.6 BW = 1060 g ± 370 Asthma = 9 (29 %) Smokers = 5 (16 %) Maternal smoking = 6 (19 %) Age at testing = 22 yr ± 2.0 RDS N = 31 (males 18, females 13) GA = 32 wk ± 3.6 BW = 1960 g ± 780 Asthma = 2 (6 %) Smokers = 2 (6 %) Maternal smoking = 3 (10 %) Age at testing = 21.0 yr ± 2.0 Preterm N = 26 (males 6, females 20) GA = 32.9wk ± 3.3 BW = 2170 g ± 800 Asthma = 3 (12 %) Smokers = 1 (4 %) Age at testing = 22.0 yr ± 2.0 Term N = 35 (males 11, females 24) GA = 39.6wk ± 1.4 BW = 3450 g ± 420 Asthma = 1 (3 %) Smokers = 3 (9 %) Maternal smoking = 1 (3 %) Age at testing = 22.0 yr ± 2.0 Participants were born in Quebec, Canada, between 1987 and 1993. The subjects were derived from four groups: (1) Preterm subjects with no neonatal respiratory complications (2) Preterm subjects with neonatal RDS (3) Preterm subjects with BPD (4) Subject born at term Study was done at the Respiratory Epidemiology and Clinical Research Unit of McGill University, Montreal, Canada. | American Thoracic Society (ATS) guidelines. Kuster SP, Kuster D, Schindler C, Rochat MK, Braun J, Held L, Brandli O. Reference equations for lung function screening of healthy never-smoking adults aged 18–80 years. Eur Respir J 2008; 31: 860–868 | BPD FEV 1 = 80.0 ± 18.0 FVC = 100.0 ± 15.0 FEV 1 /FVC = 70.0 ± 12.0 FEF 25-75% = 68.0 ± 26.0 RDS FEV 1 = 94.0 ± 12.0 FVC = 99.0 ± 9.0 FEV 1 /FVC = 81.0 ± 9.0 FEF 25-75% = 92.0 ± 19.0 Preterm FEV 1 = 94.0 ± 14.0 FVC = 104.0 ± 14.0 FEV 1 /FVC = 79.0 ± 7.0 FEF 25-75% = 89.0 ± 26.0 Term FEV 1 = 98.0 ± 9.0 FVC = 109.0 ± 10.0 FEV 1 /FVC = 79.0 ± 7.0 FEF 25-75% = 96.0 ± 18.0 | Definition not stated. |
| Lasry, 2022 “Cardiopulmonary Function Abnormalities in Cohort of Adults following Bronchopulmonary Dysplasia as Preterm Infants” | Single-center based, longitudinal study | “To describe the cardiopulmonary profiles of adult patients with broncopulmonary dysplasia (BPD), comparing them to normative adult values” | Preterm with BPD N = 44 GA = 26.4wk ± 2.7 BW = 793 g ± 175 Age at testning = 19 yr ± 4.7 Born between january 1990 and December 2000. | ATS/ERS guidelines Unknown. | Preterm with BPD FEV 1 = 74.1 ± 18.6 FVC = 80.7 ± 20.5 FEV 1 /FVC = 82.5 ± 13.6 Median (range) FEV 1 = 71.5 (28–––111) FVC = 82 (27–––119) FEV 1 /FVC = 81 (51–––109) | |
| Moschino, 2018 “Longitudinal assessment of lung function in BPD survivors from birth to Adulthood” | Center based, longitudinal study | Preterm w/BPD N = 17 (males 7, females 10) GA = 28.1wk ± 1.8 (range 26–30) BW = 930 g ± 220 (range 570–1220) Antenatal steroids = 10 (59 %) Surfactant = 12 (71 %) Age at testing 20 years 24 years 17 consecutive survivors were born at the regional NICU of Padova University Hospital between 1991 and 1993. | ATS/ERS guidelines, with a 10-L water bell spirometer (Biomedin, Italy). Global Lung Initiative | 20 years FEV 1 = 79.9 ± 18.9 FVC = 86.3 ± 15.1 FEV 1 /FVC = 90.9 ± 11.8 FEF 25-75% = 69.4 ± 27.7 zFEV 1 = -1.73 ± 1.65 zFVC = -1.25 ± 1.41 zFEV 1 /FVC = -0.91 ± 1.28 zFEF 25-75% = −1.59 ± 1.52 24 years FEV 1 = 64.1 ± 18.6 FVC = 82.3 ± 10.8 FEV 1 /FVC = 89.8 ± 11.5 FEF 25-75% = 50.3 ± 20.9 zFEV 1 = -2.14 ± 1.74 zFVC = -1.58 ± 1.71 zFEV 1 /FVC = -1.03 ± 1.32 zFEF 25-75% = −1.93 ± 1.55 | BPD defined as oxygen dependence at 28 days of life. | |
| Saarenpaa, 2015 “Lung Function in Very Low Birth Weight Adults” | Population based, cross-sectional study | «The association of lung function in young adulthood with preterm birth at VLBW and with BPD and other prenatal and neonatal conditions” | BPD N = 29 (males 13, females 16) GA = 27.9wk ± 2.4 BW = 982 g ± 228 Surfactant = 2 (6.9 %) RDS = 25 (86.2 %) Asthma = 3 (11.1 %) Current smoking = 2 (7.4 %) Maternal smoking = 5 (17.2) Age at testing = 21.7 yr ± 2.4 Non-BPD N = 131 (males 55, females 76) GA = 29.5 ± 2.1 BW = 1157 g ± 203 Surfactant = 5 (3.8 %) RDS = 52 (39.7 %) Asthma = 19 (14.7 %) Current smoking = 36 (27.7 %) Maternal smoking = 24 (18.3 %) Age at testing = 22.5 yr ± 2.0 VLBW N = 160 (males 68, females 92) GA = 29.2wk ± 2.2 BW = 1126 g ± 218 Surfactant = 7 (4.4 %) RDS = 77 (48.1 %) Asthma = 22 (14.1 %) Current smoking = 38 (24.2 %) Maternal smoking = 29 (18.1 %) Age at testing = 22.4 yr ± 2.1 Controls N = 162 (males 67, females 95) GA = 40.1 ± 1.1 BW = 3599 g ± 466 Asthma = 21 (13.0 %) Current smoking = 48 (29.6 %) Maternal smoking = 26 (16 %) Age at testing = 22.5 yr ± 2.2 The participants are from the Helsinki Study of Very Low Birth Weight Adults, born between 1978 and 1985. Of the original 335 consecutive infants, 255 subjects were asked to participate. 166 VLBW subjects accepted the invitation. Of them, 29 subjects, the BPD-group, met the inclusion-criteria for our study. | American Thoracic Society/European Respiratory Society standard. Global Lung Initiative | BPD FEV1 = 82.7 ± 14.4 FVC = 90.4 ± 11.8 FEV1/FVC = 91.3 ± 10.7 zFEV 1 = -1.01 ± 1.23 zFVC = -0.64 ± 1.01 zFEV 1 7FVC = -0.57 ± 1.38 zFEF 25-75% = −1.02 ± 1.45 FEV 1 (L) = 3.26 ± 0.82 FVC (L) = 3.96 ± 0.87 FEV 1 /FVC = 82.23 ± 9.82 FEF 25-75% = 3.40 ± 1.42 Non-BPD FEV1 = 93.5 ± 14.3 FVC = 94.6 ± 14.8 FEV1/FVC = 99.4 ± 8.9 zFEV 1 = -0.09 ± 1.35 zFVC = -0.30 ± 1.26 zFEV 1 7FVC = 0.42 ± 1.29 zFEF 25-75% = −0.01 ± 1.26 FEV 1 (L) = 3.77 ± 0.81 FVC (L) = 4.30 ± 1.02 FEV 1 /FVC = 88.34 ± 8.13 FEF 25-75% = 4.33 ± 1.29 VLBW FEV1 = 91.5 ± 14.9 FVC = 93.8 ± 14.3 FEV1/FVC = 97.9 ± 9.7 zFEV 1 = -0.25 ± 1.37 zFVC = -0.37 ± 1.22 zFEV 1 7FVC = 0.24 ± 1.35 zFEF 25-75% = −0.19 ± 1.35 FEV 1 (L) = 3.67 ± 0.83 FVC (L) = 4.24 ± 1.00 FEV 1 /FVC = 87.23 ± 8.75 FEF 25-75% = 4.16 ± 1.36 Controls FEV1 = 96.9 ± 12.8 FVC = 95.2 ± 13.3 FEV1/FVC = 102.3 ± 7.6 zFEV 1 = 0.10 ± 1.18 zFVC = -0.34 ± 1.12 zFEV 1 7FVC = 0.77 ± 1.12 zFEF 25-75% = 0.33 ± 1.10 FEV 1 (L) = 4.10 ± 0.83 FVC (L) = 4.57 ± 1.01 FEV 1 /FVC = 90.23 ± 6.83 FEF 25-75% = 4.85 ± 1.26 | BPD defined by spplemental oxygen provided at 28 days of age. |
| Um-Bergström, 2019 “Pulmonary outcomes in adults with a history of Bronchopulmonary Dysplasia differ from patients with asthma” | Population based, cross sectional study | “That pulmonary outcomes and health-related quality of life (HRQoL) were different in adults born preterm with and without a history of BPD compared to asthmatics and healthy individuals” | BPD N = 26 (males 11, females 15) GA = 26wk (24–31) BW = 960 g (583–1510) Surfactant = 8 (31 %) Maternal smoking = 7 (27 %) Prenatal steroids = 11 (42 %) Age at testing = 19.6 yr (18.2 – 21.2 ) Non-BPD N = 23 (males 10, females 13) GA = 29.5wk (26–32) BW = 1470 g (659–2200) Surfactant = 2 (9 %) Maternal smoking = 3 (13 %) Prenatal steroids = 10 (43 %) Age at testing = 19.1 yr (18.3 – 22.4) Asthma N = 23 (males 10, females 13) GA = 40wk (38–42) BW = 3505 g (2660 – 4840) Maternal smoking = 2 (9 %) Age at testing = 20.2 yr (18.6–23.3) Controls N = 24 (males 12, females 12) GA = 40wk (37–43) BW = 3458 g (2670–4550) Maternal smoking = 5 (21 %) Age at testing = 20.5 yr (18.3 – 23.8) Four study groups: (1) Preterm with BPD (2) Preterm without BPD (3) Born at term with asthma (4) Controls Group 1 and 2 recruited the subjects from a pre-existing cohort at Sachs’ Children and Youht Hospital, Södersjukhuset, Stockholm, Sweden, born between 1992 and 1998. | American Thoracic Society/European Respiratory Society guidelines. Global Lung initiative | BPD FEV 1 = 88.9 (81.4; 99.1) FVC = 96 (85.6; 101.7) FEV 1 /FVC = 0.82 (0.79; 0.85) zFEV 1 = -0.94 (-1.57; −0.08) zFVC = -0.32 (-1.24; 0.14) zFEV 1 /FVC = -0.67 (-1.86; 0.18) Non-BPD FEV 1 = 103.3 (96.9; 113.3) FVC = 96.9 (92.2; 107.5) FEV 1 /FVC = 0.91 (0.87; 0.94) zFEV 1 = 0.28 (-0.27; 1.18) zFVC = -0.26 (-0.64; 0.60) zFEV 1 /FVC = 0.82 (0.13; 1.33) Asthma FEV 1 = 101.7 (94.1; 109.0) FVC = 101.6 (94.5; 110.4) FEV 1 /FVC = 0.86 (0.83; 0.89) zFEV 1 = 0.14 (-0.52; 0.77) zFVC = 0.13 (-0.48; 0.85) zFEV 1 /FVC = -0.20 (-0.43; 0.33) Controls FEV 1 = 108.9 (99.7; 114.1) FVC = 104.6 (97.9; 109.8) FEV 1 /FVC = 0.90 (0.87; 0.93) zFEV 1 = 0.78 (-0.03; 1.26) zFVC = 0.37 (-0.18; 0.85) zFEV 1 /FVC = 0.42 (-0.26; 0.89) | BPD defined as supplemental oxygen for at least 28 days after birth. |
| Wong, 2008 “Emphysema in young adult survivors of moderate-to-severe bronchopulmonary dysplasia” | Center based, cross-sectional study | “Describe the functional and structural pulmonary sequelae of moderate and severe BPD in a population of adult survivors” | BPD N = 21 (males 9, females 12) GA = 27wk (24–30) BW = 895 g (635–1355) Age at testing = 19 (17 – 33) Participants were born at King Edward Memorial Hospital, Subiaco, Australia between 1980 and 1987. In total 21 subjects were recruited from a complete neonatal database, based on the requirement of oxygen at 36 weeks PMA. | American Thoracic Society guidelines. The z-scores for the forced expiratory volume in one second (FEV1) and FEF at 25–75 % of forced vital capacity (FVC; FEF2575%) were calculated using the equations of KNUDSON et al., the z-scores for lung volumes were calculated according to CRAPO et al. | BPD FEV 1 = 89.0 (22.6; 121.9) FEF 25-75% = 63.7 (6.1; 117.2) zFEV 1 = -0.77 (-8.20; −1.37) zFEF 25-75% = −1.81 (-6.00; −0.75) | BPD defined as continued dependence on supplementary oxygen for ≥28 days post-partum. |
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