TABLE 4

Studies assessing long-term respiratory outcomes of surfactant treatment in preterm infants

First author [ref.]Patients nBirthweight; GAAge at time of study#MethodsPrimary outcomeResultsCriticisms
Walti [56]43 (13 surfactant + 9 nonsurfactant + 21 control)N/A1 yearNot detailed; only abstract is availablePulmonary functionSurfactant does not affect long-term pulmonary function at 1 year of ageNot detailed; only abstract is available
Couser [57]47 (30 surfactant + 17 control)N/A2 yearsNot detailed; only abstract is availablePulmonary function and morbidityNo 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/A7 monthsNot detailed; only abstract is availablePulmonary functionSurfactant group had lower resistance and higher conductanceNot detailed; only abstract is available
Abbasi [55]47 (34 surfactant + 13 control)N/A3–6 months and 9–12 monthsNot detailed; only abstract is availablePulmonary functionSurfactant group had lower resistance and resistive WOB and airflow obstructionNot detailed; only abstract is available
Pelkonen [59]60 (40 preterm + 20 term control)<30 weeks7–12 yearsBicentre 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 spirometryPulmonary functionNo significant differences in spirometric measurements between the three groupsSmall 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 weeks6 yearsObservational study. Surfactant versus placebo. Parent questionnaires. PFT: spirometry, whole-body plethysmography and test of bronchial hyperreactivityPulmonary function and morbidityNo difference between the two groups in pulmonary morbidity, FRC, resistance, FEV1 or bronchial hyperreactivity. Only FEF25 was significantly lower in surfactant groupSample 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 weeks10–18 yearsPopulation-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 provocationPulmonary function and morbidityPreterms 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 approximatelyLow 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 weeks10 yearsMulticentre (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 meterPulmonary function and morbidityRespiratory 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 eraThe 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 yearsObservational 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 plethysmographyPulmonary function and morbidityAbnormalities 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 BPDLow 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 above8 yearsTwo population cohorts born in 1991–1992 and 1997, when higher rates of antenatal corticosteroids and surfactant were administered. Parental questionnaires. PFT: spirometry, whole-body plethysmographyPulmonary function and morbidityPreterm children born in both eras had substantially reduced lung function compared with controls for FEV1, FVC, FEF25–75%, and FEV1/FVCAs above. Absence of exercise testing
Doyle [63]363 (209 preterms + 154 term control)As above18 yearsObservational study. Children born in 1991–1992. Patient questionnaires. PFT: spirometry at baseline and postbronchodilatorPulmonary functionPreterms 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 salbutamolAs 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 weeks1982–1985 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: spirometryPulmonary function and morbidityNo 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 subgroupsBesides 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 above1991–1992 cohort: at 10 and 18 years
1999–2000 cohort: at 11 years
As above. Parental or patient respiratory questionnaires. PFT: spirometry, FeNO and DLCOPulmonary function and morbidityFor 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 treatmentBesides 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.