Respiratory morbidity in preterm infants predicted by natriuretic peptide (MR-proANP) and endothelin-1 (CT-proET-1)

Abstract

Background: Bronchopulmonary dysplasia (BPD) is a major complication in preterm infants <32 weeks. We aimed to assess whether plasma levels of mid-regional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET-1) predict respiratory morbidity.

Methods: This was a prospective, two-center, observational cohort study. MR-proANP and CT-proET-1 were measured at day 7 (±2) of life. Associations with duration of supplemental oxygen and the composite outcome of moderate or severe BPD or death (BPD/death) were investigated.

Results: Two hundred and twenty-nine infants <32 weeks were included (median gestational age [GA] 29.6 weeks [interquartile range 29.0-30.7], median birth weight 1150 g [IQR 840-1410]). MR-proANP and CT-proET-1 were associated with the duration of supplemental oxygen in univariable analysis (both p < 0.001) but not after adjusting for co-factors. Infants with BPD/death showed higher plasma levels of MR-proANP (623.50 pmol/L [IQR 458.50-881.38] vs. 308.35 pmol/L [IQR 216.72-538.10]; p < 0.001) and CT-proET-1 (255.40 pmol/L [IQR 202.60-311.15] vs. 198.30 pmol/L [IQR 154.70-297.95]; p = 0.015) compared to infants without BPD/death. Levels of both biomarkers were significantly associated with BPD/death in univariable models but not after adjusting for co-factors.

Conclusions: MR-proANP and CT-proET-1 are associated with the duration of supplemental oxygen and the composite outcome BPD/death, but their prognostic value does not complement that of clinical risk factors.

Impact: Plasma levels of MR-proANP and CT-proET-1, measured on day 7 of life (±2 days) are associated in univariable analyses with duration of supplemental oxygen and the combined outcome of BPD or death in VLGA infants. Associations between both biomarkers and respiratory morbidity do not persist in multivariable models, in particular when gestational age is included. MR-proANP and CT-proET-1 have limited additional value to predict respiratory morbidity in VLGA infants compared to clinical parameters.

Fig. 1

Flow chart of patient recruitment.

Fig. 2. Association of biomarkers with the duration of supplemental oxygen.

a Association of Log10 transformed levels of MR-proANP with duration of supplemental oxygen. b Association of Log10 transformed levels of CT-proET-1 with duration of supplemental oxygen. Circles represent patients without development of BPD/death; crosses show patients with BPD/death.

Fig. 3. ROC curves for the fitted logistic regression models with BPD/death as dependent variable.

a Independent variables are gestational age (solid, AUC 0.85 (95% CI [0.77, 0.93])), MR-proANP (dotted, AUC 0.76 [0.65, 0.86]), CT-proET-1 (dot-dashed, AUC 0.61 [0.51, 0.72]), and a composite variable of MR-proANP and CT-proET-1 (dashed, AUC 0.72 [0.61, 0.83]). b Independent variables are those included in the NICHD BPD risk estimator (solid, AUC 0.86 [0.76, 0.95]), composite variable of NICHD BPD risk estimator variables plus MR-proANP (dotted 0.84 [0.72, 0.95]), composite variable of NICHD BPD risk estimator variables plus CT-proET-1 (dot-dashed, AUC 0.82 [0.69, 0.95]), and composite variable of NICHD plus MR-proANP plus CT-proET-1 (dashed, AUC 0.83 [0.71, 0.95]). AUC area under the curve.