Figures
- FIGURE 1
Patient disposition. Flow chart of the participants. Seven healthy prematurely (HP) born infants could not be located for the study. However, one subject, who was not measured in infancy, could be included in the adult group. Three refused to participate and one moved abroad leaving 14 HP participants. Of the hyaline membrane disease (HMD) subjects, 5 could not be located at adult age leaving 14 HMD participants. Of those with bronchopulmonary dysplasia (BPD), 2 passed away during infancy, 2 could not be located, 2 have moved abroad, 3 refused to participate and 3 were severely mentally handicapped, precluding them to participate at adulthood leaving 36 BPD participants. As clinical data of HP and HMD groups revealed no differences (supplementary table S1), all data of these two groups were combined to qualify as non-BPD (non-BPD, n=28). Thus, in total, 28 non-BPD served as controls and 36 BPD subjects were analysed in the study. All HP subjects were White except for one from Indonesia and two from North African, one HMD and one BPD subject was from Indonesia.
- FIGURE 2
Spirometry, gas exchange and lung density at young adulthood. Box plots for lung function parameters of 28 non-BPD subjects (dark box) and 36 BPD subjects (light box) who had spirometry, gas transfer and lung density measured. *: significant difference between groups after correction for birth weight and smoking history (p<0.005);. +: outlier.
- FIGURE 3
Distribution of forced expiratory volume in 1 s (zFEV1) with and without airway obstruction in the bronchopulmonary dysplasia (BPD) group. In the BPD group (55%) had a normal zFEV1/forced vital capacity (FVC) (defined by z-score >−1.64), 16 of whom had a zFEV1 above the lower limit of normal (LLN), while those with a zFEV1/FVC below the LLN (n=15 of 33) had a mean zFEV1 of −3.09, (−4.89 to −1.22, min to max).
- FIGURE 4
Relation between inspiratory oxygen fraction (FIO2) at 36 weeks of gestational corrected age (GCA) and forced expiratory volume in 1 s (zFEV1) or zFEV1/forced vital capacity (FVC) at adulthood. Airflow limitation (zFEV1) and airway obstruction (zFEV1/FVC) in 29 NCLD adult subjects in relation to the FIO2 at 36 weeks after conception measured while treated with oxygen administered to the spontaneously breathing infant, either in an incubator or in an oxygen tent. Regression analysis for zFEV1 revealed B=−6.4, with p=0.053, and B=−3,2, with p=0.29 for zFEV1/FVC.
Tables
- TABLE 1
Perinatal characteristics and at gestational corrected age (GCA) of 1 year
Non-BPD group (n=28) BPD group (n=36) Missing (BPD/non-BPD) p-value Male 18/28 (64%) 24/36 (67%) 0 0.84 Weeks of pregnancy 31.0±2.6 28.2±2.3 0 <0.0001 Birth weight g 1484±440 1059±334 0 <0.0001 Birth weight percentiles 52.5±29.6 51.6±31.3 0 0.91 Surfactant therapy 11/28 (39%) 21/36 (58%) 0 0.13 Prenatal dexamethasone# 7/28 (25%) 16/36 (44%) 0 0.11 Postnatal dexamethasone 0/28 (0%) 20/36 (56%) 0 <0.0001 HMD 14/28 (50%) 27/36 (75%) 0 0.036 PIPmax 8.2±10.9 24.7±7.5 5/5 <0.0001 FIO2 at 36 weeks 0.21 0.29±0.08 6/0 <0.0001 GCA at lung function testing months 9.7±3.8 10.4±3.0 1/1 0.47 CHL at lung function testing cm 71±9 71±7 2/1 0.73 FRC z-score for CHL 0.05±1.03) 0.37±1.31 2/1 0.30 Compliance z-score for CHL 0.32±1.03 −0.56±0.82 3/1 0.0005 Mixing efficiency % 56±10 43±17 2/2 0.0012 Data are presented as mean±sd or n/N (%), unless otherwise stated. Mean weeks of pregnancy and mean birth weight were significantly different between groups. GCA in months for some patients was less than 12 months because they could not be tested at GCA 12 months. Mean PIPmax: mean maximum positive inspiratory pressure during mechanical ventilation in cmH2O; mean FIO2 at 36 weeks: fractional inspired oxygen concentration in ambient air at post-conceptional age of 36 weeks; GCA: gestational corrected age; BPD: bronchopulmonary dysplasia; CHL: crown–heel length; HMD: hyaline membrane disease; PIPmax: maximum positive inspiratory pressure; FIO2: inspiratory oxygen fraction. #: Prenatal dexamethasone was administered ante partum to mothers if admitted on time before delivery to the hospital.
- TABLE 2
Subject characteristics at adulthood
Non-BPD group (n=28) BPD group (n=36) Missing p-value Smoking 4/28 (14%) 7/36 (19%) 0 0.74 Age at lung function testing years 21.0±2.5 19.7±1.1 0 0.0077 Weight kg 68±12 69±19 0 0.89 Length cm 177±10.3 174±10 0 0.21 BMI kg·m−2 21.7±2.8 22.6±4.9 0 0.38 Data are presented as mean±sd or n/N (%), unless otherwise stated. BPD: bronchopulmonary dysplasia; Smoking: ever-smoking (yes=1, no=0); BMI: body mass index kg·m−2.
- TABLE 3
Regression analysis of perinatal parameters on outcomes in adult BPD
zFEV1/FVC zFEV1 zDLCO SMS SGRQ FIO2 36w (B (p)) −3.2 (0.29) −6.4 (0.053) −4.1 (0.023) −2.4 (0.36) 3.7 (0.86) Prenatal dexa (B (p)) −0.64 (0.24) 0.19 (0.74) 0.56 (0.069) −0.77 (0.097) 4.2 (0.27) Birthweight g (B (p)) −0.0023 (0.0091) −0.0015 (0.089) 0.0097 (0.043) 0.0014 (0.075) 0.0065 (0.28) PIPmax (B (p)) 0.028 (0.51) 0.028 (0.53) 0.0020 (0.93) −0.020 (0.55) −0.093 (0.74) R2 adjusted (adjusted p-values of likelihood ratio test) 0.20 (0.046) 0.16 (0.081) 0.17 (0.057) 0.13 (0.10) −0.057 (0.67) Multiple linear regression analyses were used to determine whether neonatal parameters correlated with outcomes at adult age within the BPD group. None of the dependent variables at adulthood reached a significance level, set at p<0.0025 by Bonferroni correction. zFEV1/FVC, zFEV1, zFVC, are z-scores for adult lung function outcomes with GLI-references and zDLCO with European Community of Coal and Steel references. Prenatal dexa: ante partum dexamethasone administered to mothers (yes=1, no=0). BPD: bronchopulmonary dysplasia; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; SMS: standard mass score for lung density; SGRQ: St. George's Respiratory Questionnaire; FIO2 36w: fractional inspired oxygen concentration in ambient air at post-conceptional age of 36 weeks; PIPmax: maximum positive inspiratory pressure during mechanical ventilation in cmH2O; DLCO: diffusing capacity of the lung for carbon monoxide.
Supplementary Material
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Supplementary material 00157-2020.SUPPLEMENT
