| OBJECTIVE Infection is a significant cause of morbidity and mortality in the newborn infants,particularly in preterm and low birth weight infants.Despite advances in neonatal care,overall case-fatality rates from severe infection are still high.Platelet-activating factor(PAF) is an important phospholipid mediator involved in sepsis,and interventions that block PAF may reduce mortality and multiple organ dysfunction.The roles of PAF and PAF-acetylhydrolase(PAF-AH),the enzyme that inactivates PAF,in neonates with severe infection have not been reported.In this study,we measured plasma PAF levels and PAF-AH activity in neonates with infection,first,to evaluate the relationship between PAF/ PAF-AH and neonatal infection;secondly,to observe the trend of PAF and PAF-AH during the course of infection;thirdly,to detect the relationship between PAF,PAF-AH,and neonatal systemic inflammatory response syndrome.METHODS Part 1:Two hundreds and forty-seven neonates who were admitted to the NICU of Children's Hospital of Fudan University from July to December in 2008 were enrolled,excluding infants with congenital malformation,inherited metabolic diseases and severe asphyxia.According to the severity of infection,the patients were divided into 3 groups:non-infection group(N=93),mild infection(including neonates with mild pneumonia,infectious diarrhea,urinary tract infection and congenital syphilis) group(N=53) and severe infection(including neonates with sepsis, meningitis and severe pneumonia) group(N=97).Plasma samples of infection groups were taken within 48h after infection,others were taken during hospitalization period. Part 2:Plasma samples were taken on the 1st,3rd,5th and 7th day of infection from 12 neonates with severe infection to observe the trend of PAF and PAF-AH during the course of infection.Part3:All the full-term infants of Part 1 and 2 were enrolled in this part.They were divided into 4 groups according to the definitions of neonatal SIRS:non-SIRS group(N=90),SIRS group(N=8),sepsis group(N=24),and severe sepsis group(N=15).The plasma PAF was measured by ELISA,and PAF-AH activity was measured using PAF Acetylhydrolase Assay Kit from Cayman Chemical Company.All statistic analyses were conducted with SPSS software,version 15.0 for windows.RESULTS Part 1:Mean plasma PAF level was significantly higher in infants with severe infection(9.29±7.94ng/ml) than those in infants with non-infection group (4.61±3.49ng/ml,P＜0.001) and mild infection group(5.24±3.19ng/ml,P＜0.001). Plasma PAF-AH activity was correlated with age,and it was higher in late stage neonates(age＞7days) than that in early stage ones(age＜7days)(P＜0.05) in all patients.In early stage or late stage neonates,plasma PAF-AH activity of severe infection group(5.61±2.62nmol/ml/min,7.02±2.48nmol/ml/min,respectively) was significantly lower than those of non-infection group(7.27±2.45 nmol/ml/min, 9.71±2.65 nmol/ml/min,respectively) and mild infection group(7.92±2.91 nmol/ml/min,9.72±2.16 nmol/ml/min,respectively).Infants with sepsis caused by Gram negative bacteria had higher plasma PAF levels and lower PAF-AH activity than those with sepsis caused by Gram positive bacteria(P＜0.05).Part 2:Plasma PAF levels and PAF-AH activity that were measured in the individual patients showed a high variability during the course of infection.In survivals,plasma PAF levels decreased notably over time(10.12±2.80ng/ml on the 1st day of infection VS 4.88±1.39ng/ml on the 7th day,P＜0.001),and PAF-AH activity markedly increased (5.59±2.36nmol/ml/min on the 1st day VS 13.47±7.41 nmol/ml/min on the 7th day, P＜0.01).In non-survivals,plasma PAF levels increased over time,and PAF-AH activity decreased or remained on a low level.Part 3:Mean plasma PAF level was significantly higher in infants of sepsis group and severe sepsis group (13.17±9.86ng/ml and 8.69±4.51ng/ml,respectively),than those in infants of non-SIRS group and SIRS group(5.10±4.04ng/ml and 4.81±1.89ng/ml,respectively). Plasma PAF-AH activity of infants in SIRS,sepsis and severe sepsis groups (5.85±1.21 nmol/ml/min,6.54±2.62nmol/ml/min,6.02±2.06 nmol/ml/min, respectively) were significantly lower than that of non-SIRS group(8.07±2.86 nmol/ml/min;P=0.001,0.019,0.010,respectively).CONCLUSIONS 1) Plasma PAF levels were directly correlated and plasma PAF-AH activity was inversely correlated with the severity of neonatal infection. Bacteria which caused infection also influenced Plasma PAF levels and plasma PAF-AH activity.2) Plasma PAF levels and PAF-AH activity showed variations during the course of infection.Single plasma PAF levels or PAF-AH activity had no correlation with the outcome of neonatal infection.However,the trend of their variations may correlate with the prognosis.3) Infants with sepsis or severe sepsis have higher plasma PAF levels and lower PAF-AH activity.
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