ABSTRACT
Objective To analyze the changes in blood metabolites in premature infants with bronchopulmonary dysplasia (BPD) within 36 h and in the 3rd week after birth in order to find new biomarkers for diagnosis of BPD.Methods The BPD group included 20 premature infants (＜32 gestational weeks) hospitalized in the Neonatal Intensive Care Unit (NICU) of the Sixth Affiliated Hospital of Sun Yat-sen University and diagnosed with BPD from January 2014 to October 2016.Another 20 non-BPD premature infants with similar gestational age (within one week) who were admitted during the same period were enrolled in the control group.Blood samples of both groups were collected within 36 h and in the 3rd week after birth.Liquid chromatography-tandem mass spectrometry was used to detect blood metabolites and the obtained data were subjected to metabolomics analysis using orthogonal partial least squares discriminant analysis.Chi-square test (or Fisher's exact test),Mann-Whitney U test or t test was used for statistical analysis.Results (1) Twenty and 11 blood samples were collected within 36 h and in the 3rd week after birth from the BPD and the control group,respectively.Compared with the control group,the interval between premature rupture of membranes and delivery,the average length of hospital stay,non-invasive and invasive mechanical ventilation duration and the total duration of supplemental oxygen during hospitalization in the BPD group were longer [M (P25-P75) or ((x)±s):13.5 (0.0-98.3) vs 0.0 (0.0-0.0) h,Z=3.049;(66.6±20.5) vs (43.9±9.3) d,t=4.574;267.0 (199.5-516.1) vs 110.5 (0.0-238.5) h,Z=-3.428;117.5 (0.0-269.3) vs 0.0 (0.0-72.0) h,Z=-2.785;(1 184.0±386.6) vs (595.9±270.3) h,t=5.576;all P＜0.05].(2) Within 36 h after birth,the levels of glycine,proline,tryptophan and piperamide-C5:1 in the BPD group were decreased obviously compared with those in the control group [(201.59±65.01) vs (290.90± 137.56) μmol/L,t=-2.625;103.55 (72.43-434.57) vs 439.48 (103.80-608.98) μ mol/L,Z=-2.245;29.54 (20.30-41.04) vs 47.42 (29.46-73.57) μ mol/L,Z=-2.326;50.04 (35.29-104.78) vs 95.79 (76.21-129.97) μmol/L,Z=-2.029;all P＜0.05].However,the glutamate level was increased [(224.30±67.40) vs (182.67±40.87) μmol/L,t=2.362,P＜0.05].(3) In the 3rd week after birth,the levels of glycine,proline and tryptophan in the BPD group were lower compared to those in the control group [(185.92±61.51) vs (271.85± 115.85) μmol/L,t=-2.177;(39.41± 18.22) vs (63.92± 17.50) μ mol/L,t=-3.217;90.23 (37.93-146.37) vs 330.15 (47.79-622.90) μ mol/L,Z=-2.134;all P＜0.05].However,the ornithine level was higher [(75.09± 43.21) vs (39.25 ± 16.53) μ mol/L,t=2.569,P＜0.05].Conclusions Glycine,proline and tryptophan in blood are potential biomarkers for early diagnosis of BPD.
ABSTRACT
Objective To study the characteristics of urinary metabolites in the premature infants with or without bronchopulmonary dysplasia (BPD) within 36 hours after birth and to find new biomarkers for the early warning indicators for BPD.Method From January 2014 to October 2016,premature infants hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University with gestational age ＜ 32 weeks,hospitalization time ＞ 28 days and urine samples were collected within 36 hours after birth for metabolite detection were enrolled in the study.Preterm infants diagnosed as BPD were selected as the BPD group.Preterm infants with the same gestational age,days of age with the BPD group had no BPD were selected as the control group at a ratio of 1 ∶ 1.The gas chromatography-mass spectrometry was used to measure the metabolites.The data were analyzed using orthogonal partial least squares discriminant analysis and receiver operating characteristic (ROC) curve and the area under which were used to determine the performance of differential metabolites in the diagnosis of BPD.Result There were 20 patients in the BPD group and 20 patients in the control group.Within 36 hours after birth,in the BPD group,the level of fucose and tartrate in urine (nmol/mgCr) were significantly lower than that in the control group [0.00 (0.00,0.03)vs.0.07 (0.00,0.41);0.00 (0.00,0.01) vs.0.02 (0.00,0.06),respectively].The level of kynurenic acid and thymine (nmol/mgCr) were significantly higher than the level in the control group [0.04 (0.00,0.43) vs.0.00 (0.00,0.00);7.10 (0.00,14.47) vs.0.00 (0.00,0.22),respectively].All the differences were statistically significant (P ＜ 0.05).ROC curve analysis showed that the area under the curve for the diagnosis of BPD in combination with the four metabolites was 0.857 (95％ CI 0.732 ～0.982).Conclusion Changes in urinary metabolites such as fucose,thymine,kynurenine and tartaric acid in preterm infants may be related to the development of BPD.Early detection of these four metabolites has potential in the early diagnosis of BPD,and may warn against the occurrence of BPD.