Urinary metabolomic analysis to identify preterm neonates exposed to histological chorioamnionitis: A pilot study.

OBJECTIVE: Chorioamnionitis is a leading cause of preterm birth worldwide, with higher incidence at lower gestational ages. An early and reliable diagnosis of histological chorioamnionitis (HCA) in preterm infants may be helpful in guiding postnatal management, especially the administration of prophylactic antibiotics to prevent early-onset sepsis. The main aim of this study was to investigate metabolomic analysis of urines collected in the first 24 hours of life as diagnostic tool of HCA. METHODS: Gestational age-, birth weight-, delivery mode- and sex- matched (1:2) preterm neonates (< 35 weeks' gestation) born to mothers with or without HCA were enrolled from an observational study. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic analysis was performed on urine samples non-invasively collected in the first 24 hours of life. Univariate analysis, partial least square discriminant analysis (PLS-DA) and its associated variable importance in projection (VIP) score were performed. The most affected metabolic pathways were examined by Metabolite Sets Enrichment Analysis (MSEA). RESULTS: Fifteen cases (mean GA 30.2 ± 3.8 weeks, mean BW 1415 ± 471.9 grams) and 30 controls (mean GA 30.2 ± 2.9 weeks, mean BW 1426 ± 569.8 grams) were enrolled. Following univariate analysis, 29 metabolites had a significantly different concentration between cases and controls. The supervised PLS-DA model confirmed a separation between the two groups. Only gluconic acid, an oxidation product of glucose, was higher in cases than in controls. All other VIP metabolites were more abundant in the control group. Glutamate metabolism, mitochondrial electron transport chain, citric acid cycle, galactose metabolism, and fructose and mannose degradation metabolism were the most significantly altered pathways (P < 0.01). CONCLUSIONS: For the first time, urinary metabolomics was able to discriminate neonates born to mothers with and without HCA. The identification of specifically altered metabolic pathways may be helpful in understanding metabolic derangement following chorioamnionitis.

Urinary ß2-microglobulin in very preterm neonates with chorioamnionitis.

It is important to identify premature infants with prenatal inflammation as it contributes to short- and long-term complications. Our object was to study how prenatal inflammation affects the urinary ß(2)-microglobulin (ß(2)-MG) level. Preterm neonates were divided based on the presence of chorioamnionitis (CAM) into the CAM (n = 100) and non-CAM groups (n = 117). These were further subdivided into five groups each: 30 preterm neonates of 23-26; 42 neonates of 27-28; 54 neonates of 29-30; 51 neonates of 31-32; and 40 neonates of 33-34 weeks' gestation. The urinary ß(2)-MG level within 48 h of birth was significantly higher in the CAM group than in the non-CAM group among the neonates of 23-26 weeks' gestation (18.3 ± 6.9 vs 10.0 ± 5.6 × 10(4) µg/gCr, p = 0.0018) and the neonates of 27-28 weeks' gestation (16.2 ± 10.8 vs 8.8 ± 3.3 × 10(4) µg/gCr, p = 0.0101). However, there was no difference in urinary ß(2)-MG level between the CAM and the non-CAM group among the neonates ≥ 29 weeks 'gestation. Moreover, the elevated urinary ß(2)-MG level in the neonates ≤ 28 weeks ' gestation with CAM had disappeared by 1 week after birth. The reasons for the increase in urinary ß(2)-MG level within 48 h of birth in very preterm neonates (≤ 28 weeks' gestation) with CAM are believed to be not only prematurity, but also prenatal inflammation. It is suggested that the urinary ß(2)-MG level during the early postnatal period can identify prenatal inflammation.

Urinary beta 2-microglobulin in premature infants with chorioamnionitis and chronic lung disease.

The urinary beta(2)-microglobulin (MG) concentration on day 0 to 2 was significantly higher in premature infants with chorioamnionitis (CAM) than in infants without CAM and in infants who developed chronic lung disease (CLD) than in those who did not. We propose that an elevated urinary beta(2)-MG can indicate a fetal inflammatory response and identify neonates at risk for the development of CLD.