First author [ref.] | Patients n | Birthweight; GA | Age at time of study# | Methods | Primary outcome | Results | Criticisms |
Walti [56] | 43 (13 surfactant + 9 nonsurfactant + 21 control) | N/A | 1 year | Not detailed; only abstract is available | Pulmonary function | Surfactant does not affect long-term pulmonary function at 1 year of age | Not detailed; only abstract is available |
Couser [57] | 47 (30 surfactant + 17 control) | N/A | 2 years | Not detailed; only abstract is available | Pulmonary function and morbidity | No differences between the two groups in terms of respiratory morbidity and function (FRC, VT, compliance, resistance and time constant) | Not detailed; only abstract is available |
Yuksel [44] | 17 (7 surfactant + 10 control) | N/A | 7 months | Not detailed; only abstract is available | Pulmonary function | Surfactant group had lower resistance and higher conductance | Not detailed; only abstract is available |
Abbasi [55] | 47 (34 surfactant + 13 control) | N/A | 3–6 months and 9–12 months | Not detailed; only abstract is available | Pulmonary function | Surfactant group had lower resistance and resistive WOB and airflow obstruction | Not detailed; only abstract is available |
Pelkonen [59] | 60 (40 preterm + 20 term control) | <30 weeks | 7–12 years | Bicentre study. Randomised into three groups: surfactant at birth (prophylactic), after development of RDS (rescue) and placebo group. Parental questionnaires and prick tests. PFT: bronchodilation test (twice daily for 4 weeks) and spirometry | Pulmonary function | No significant differences in spirometric measurements between the three groups | Small sample size. Children born in 1983–1987. The strategy of ventilation support used was not described |
Gappa [58] | 40 (22 surfactant + 18 term control) | Mean 1100 g; 25–30 weeks | 6 years | Observational study. Surfactant versus placebo. Parent questionnaires. PFT: spirometry, whole-body plethysmography and test of bronchial hyperreactivity | Pulmonary function and morbidity | No difference between the two groups in pulmonary morbidity, FRC, resistance, FEV1 or bronchial hyperreactivity. Only FEF25 was significantly lower in surfactant group | Sample size. Children born in 1987–1988. Lack of statistical power for no cooperation during lung function tests |
Halvorsen [16] | 162 (81 preterm + 81 term control) | <1000 g; <28 weeks | 10–18 years | Population-based, controlled study. Children born in 1982–1985 (no surfactant) and in 1991–1992 (49% received surfactant). BPD definition proposed by Jobe and Bancalari [3]. Test for atopy: skin prick test and specific IgE. Parental questionnaires. PFT: spirometry, body plethysmography and methacholine provocation | Pulmonary function and morbidity | Preterms had similar long-term decreases in lung outcome: BPD incidence, airway obstruction, hyperresponsiveness and pulmonary hyperinflation. Similar significant airway obstruction in the two birth cohorts: oxygen supplementation was associated with long-term negative effects on FEV1 only if lasting >1 month approximately | Low experience in surfactant therapy, administered as recue therapy. Pulmonary function was assessed at a mean age of 17.7 years in children born in 1980s and at a mean age of 10.4 years in children born in 1990s |
Palta [61] | 625 (265 VLBW + 360 term control) | <1500 g (mean 1123 g); mean 29 weeks | 10 years | Multicentre (six centres) prospective study. During 1988–1991, three surfactant periods: 1) sporadic RCTs; 2) investigational new drug; and 3) general release. Parental respiratory questionnaires. PFT: electronic peak flow meter | Pulmonary function and morbidity | Respiratory abnormalities persist to age 10 years for VLBW children born in the surfactant era. Baseline test results did not differ across birth years, but PEF variation and FVC were less in the postsurfactant era | The study may have been insufficiently powered to statistically detect a decrease in FVC postsurfactant |
VICS trial | |||||||
Doyle [60] | 448 (240 preterms + 208 term control) | <1000 g; <28 weeks | 8 years | Observational study. Children born in 1991–1992. Surfactant as rescue therapy. BPD defined as oxygen dependency at 36 weeks PMA. Parental questionnaires. PFT: spirometry, whole-body plethysmography | Pulmonary function and morbidity | Abnormalities in respiratory function and asthma incidence in very preterm children compared with control subjects described in the presurfactant era persisted in the 1990s, especially in those who had BPD | Low experience in surfactant therapy (surfactant has been used in Victoria since 1991). Surfactant used only as rescue therapy and only in with the most severe lung disease |
Hacking [64] | 1991–1992 cohort: 448 (240 preterm + 208 term control) 1997 cohort: 299 (150 preterm + 149 term control) | As above | 8 years | Two population cohorts born in 1991–1992 and 1997, when higher rates of antenatal corticosteroids and surfactant were administered. Parental questionnaires. PFT: spirometry, whole-body plethysmography | Pulmonary function and morbidity | Preterm children born in both eras had substantially reduced lung function compared with controls for FEV1, FVC, FEF25–75%, and FEV1/FVC | As above. Absence of exercise testing |
Doyle [63] | 363 (209 preterms + 154 term control) | As above | 18 years | Observational study. Children born in 1991–1992. Patient questionnaires. PFT: spirometry at baseline and postbronchodilator | Pulmonary function | Preterms had a greater small airway obstruction between 8 and 18 years. Within the preterm group, those who had BPD and were smokers had even more airway obstruction increased over time. Within the preterm group, only those with BPD, but not smokers, had a larger response in FEV1 to salbutamol | As above. Low follow-up at age 18 years and incomplete data for smoking from the patients' questionnaires |
Vollsæter [62] | 1982–1985 cohort: 92 (46 preterm + 46 term control) 1991–1992 cohort: 70 (35 preterm + 35 term control) | <1000 g; <28 weeks | 1982–1985 cohort: at 18 and 25 years 1991–1992 cohort: at 10 and 18 years | Prospective longitudinal study. Two population cohorts born in 1982–1985 and 1991–1992, when surfactant was for selective administration in the Osiris trial. BPD defined as oxygen dependency at 36 weeks PMA. Parental questionnaires. PFT: spirometry | Pulmonary function and morbidity | No differences between the two population cohorts born in 1982–1985 and 1991–1992. Preterm-born cohorts, particularly those with BPD, had significantly lower FEV1 and FEF25–75%. FEV1 was stable at ages 10–18 years and at ages 18–25 years in all subgroups | Besides surfactant, other significant changes from 1982–1985 to 1991–1992: fewer ventilator days, more use of antenatal and postnatal steroids and lower GA |
Vollsæter [65] | 1991–1992 cohort: 70 (35 preterm + 35 term control) 1999–2000 cohort: 111 (57 preterm + 54 term control) | As above | 1991–1992 cohort: at 10 and 18 years 1999–2000 cohort: at 11 years | As above. Parental or patient respiratory questionnaires. PFT: spirometry, FeNO and DLCO | Pulmonary function and morbidity | For children with BPD, important lung function variables were better in 1999–2000 compared to 1991–1992 and improvements were related to more use of antenatal corticosteroids and surfactant treatment | Besides surfactant, other significant changes from 1991–1992 to 1999–2000: more extensive use of antenatal corticosteroids, better perinatal care and better exploitation of technologies, such as A/C ventilation and HFOV. Sample size |
GA: gestational age; VICS: Victorian Infant Collaborative Study; N/A: not available; FRC: functional residual capacity; VT: tidal volume; WOB: work of breathing; RDS: respiratory distress syndrome; PFT: pulmonary function test; IgE: immunoglobulin E; FEV1: forced expiratory volume in 1 s; FEFn: forced expiratory flow at n% of the forced vital capacity (FVC); BPD: bronchopulmonary dysplasia; VLBW: very low birthweight; RCT: randomised controlled trial; PEF: peak expiratory flow; PMA: postmenstrual age; FeNO: exhaled nitric oxide fraction; DLCO: diffusing capacity of the lung for carbon monoxide; A/C: assist-control; HFOV: high-frequency oscillatory ventilation. #: ages at the study time are given in corrected age.