Postnatal changes of cytokines in premature infants with or without funisitis.

OBJECTIVE: Fetal inflammatory response syndrome (FIRS), which induces hypercytokinemia, is important for the outcomes of premature infants. It is necessary to focus on the fetal inflammatory environments. METHODS: A total of 37 premature infants (gestational age ≤32 weeks) were divided into three groups: (1) 15 without chorioamnionitis (CAM) and funisitis; C(-)F(-) group, (2) 15 with CAM but without funisitis; C(+)F(-) group and (3) 7 with CAM and funisitis; C(+)F(+) group. Blood interleukin (IL)-1ß, IL-6 and IL-8 levels were measured on day 0 (= in umbilical cord blood), 3, 7, 14, 21 and 28. RESULTS: (1) day 0: Cord blood concentrations of IL-1ß, IL-6 and IL-8 were significantly higher in the C(+)F(+) group than in the C(+)F(-) group and C(-)F(-) group. On the other hand, they were comparable between the C(+)F(-) group and C(-)F(-) group. (2) Days 3-28: elevated cytokines levels in the C(+)F(+) group with funisitis decreased on day 3 and later. CONCLUSIONS: We suggested that hypercytokinemia in the cord blood in premature infants were greatly related with funisitis. Diagnosis of funisitis would be important to find the premature infants who need to be managed their risk of FIRS. In addition, hypercytokinemia disappeared in a few days after birth; therefore, cord blood data analysis of cytokines and/or inflammation-related proteins concentrations is necessary to evaluate the fetal inflammatory environments in premature infants after birth.

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.

Severity of chorioamnionitis and neonatal outcome.

AIM: The aim of this study is to elucidate whether the stage of chorioamnionitis is or is not associated with the development of neonatal diseases. MATERIAL & METHODS: We reviewed the neonatal intensive care unit discharge files and placental pathology reports of 302 preterm infants. The presence of various stages of chorioamnionitis as well as absence of an association with chorioamnionitis (non-chorioamnionitis) were compared among neonatal diseases. RESULTS: Preterm infants were grouped according to three stages of chorioamnionitis or the absence of an association with chorioamnionitis. Gestational age differed significantly between these groups. Before controlling for gestational age, the chorioamnionitis stage was significantly higher among infants with chronic lung disease, retinopathy of prematurity and intraventricular hemorrhage than in infants without these diseases. On the other hand, the chorioamnionitis stage was lower in infants with respiratory distress syndrome than without. After controlling for gestational age, the stage of chorioamnionitis was significantly lower in infants with respiratory distress syndrome than in infants without respiratory distress syndrome, whereas, significant differences were not detected between the presence and absence of chronic lung disease, retinopathy of prematurity and intraventricular hemorrhage. Furthermore, gestational age was a significant risk factor for chronic lung disease, respiratory distress syndrome, retinopathy of prematurity and intraventricular hemorrhage. CONCLUSIONS: We found no significant differences in stages of chorioamnionitis between infants with and without neonatal diseases except for respiratory distress syndrome. A significant inverse relationship was observed between the stage of chorioamnionitis and development of respiratory distress syndrome.

Early discharge from a neonatal intensive care unit and rates of readmission.

BACKGROUND: Increasing admissions to neonatal intensive care units (NICUs) demand early discharge from the units. Our hospital aims to early discharge patients who meet the following requirements: they are able to regulate body temperature; neither apnea nor bradycardia is observed; and bodyweight increases with lactation. We studied the real state of this strategy. METHODS: We looked at postmenstrual age, bodyweight, complication at the time of discharge and the readmission rate in 609 patients with gestational age of less than 34 weeks, who were discharged from our NICU between January 2000 and March 2008. RESULTS: The postmenstrual age and bodyweight at discharge decreased with the increase of gestational age. This tendency was stronger in cases with gestational age of less than 26 weeks. A comparison was made between two patient groups with a gestational age of less than 26 weeks and with the age of 26 weeks or longer. Many patients with a gestational age of less than 26 weeks suffered frequently from complications and were on home oxygen therapy. The readmission rates within 3 months and 1 year of NICU discharge were 10.4% and 26.9% in patients with gestational age between 22 and 25 weeks, respectively, while those rates were 2.8% and 7.4% in patients with gestational weeks of 26 to 34, respectively. CONCLUSION: The postmenstrual age and bodyweight at NICU discharge decreased in inverse proportion to gestational age, especially less than 26 weeks. Our requirements for early discharge were verified by the readmission rate in this investigation.

Soluble tumor necrosis factor receptor-1 in preterm infants with chronic lung disease.

BACKGROUND: It is clear that inflammation plays an important role in developing chronic lung disease in preterm infants. The purpose of the present study is to investigate changes of serum soluble tumor necrosis factor receptor-1 levels over time in infants with chronic lung disease. METHODS: The serum levels of soluble tumor necrosis factor receptor-1 were measured after delivery, and at 7, 14, 21 and 28 days of age in 10 infants with chronic lung disease and in 18 infants without chronic lung disease. RESULTS: The serum level of soluble tumor necrosis factor receptor-1 was significantly higher in infants with chronic lung disease than in infants without chronic lung disease after delivery. The differences between these two groups remained up to 28 days of age. CONCLUSION: Prenatal inflammation with persistence into postnatal inflammation may be involved in the onset of chronic lung disease.

Soluble tumor necrosis factor receptor-I in preterm infants with chorioamnionitis.

AIM: The aim of our study was (i) to determine whether chorioamnionitis (CAM) is associated with an elevated soluble tumor necrosis factor receptor I (sTNFR-I) level and (ii) to examine the time course of the concentration of sTNFR-I in preterm infants after birth. METHODS: We measured sTNFR-I levels in the cord blood of 112 preterm infants (gestational age < or =34 weeks), and those in peripheral blood of 30 preterm infants on days 7, 14, 21 and 28. RESULTS: The median value for the sTNFR-I was significantly elevated in 33 infants with CAM at stage 3 (4618 pg/mL) compared with the 52 infants without CAM (2866 pg/mL), or the 13 infants with CAM at stage 1 (3638 pg/mL) and the 14 infants at stage 2 (3242 pg/mL). The severity of CAM is an independent factor for the elevation of cord blood sTNFR-I. The sTNFR-I level on day 0 was significantly higher in eight infants with CAM at stage 3 than in the 22 infants without CAM or with CAM at stage 1 and 2; however there were no significant differences on days 7, 14, 21 and 28. The serum level of sTNFR-I showed a significant gradual decline with time. CONCLUSIONS: We suggest that there is an association between elevated sTNFR-I levels in cord blood and maternal CAM, and this elevation may reflect the fetal inflammation. However the elevation of sTNFR-I could not persist postnatally for a long time.

Comparison of markers for fetal inflammatory response syndrome: fetal blood interleukin-6 and neonatal urinary beta(2)-microglobulin.

AIM: Chronic lung disease (CLD) is a major component in the morbidity of premature infants suffering from fetal inflammatory response (FIRS). The aim of the present study was to compare the value of measuring neonatal urinary beta(2)-microglobulin (beta(2)-MG) levels with fetal blood interleukin (IL)-6 levels in premature infants at risk of developing CLD. METHODS: Premature infants (gestational age <30 weeks) without CLD (n = 19) and with CLD (n = 10) were enrolled. We measured IL-6 levels in umbilical cord blood and beta(2)-MG levels in urine obtained within 48 h after birth. RESULTS: IL-6 and beta(2)-MG levels were significantly higher in infants who developed CLD than in those who did not (median IL-6, 54.7 vs 7.6 pg/mL; P < 0.005; beta(2)-MG 17.7 vs 9.3 x 10(4) microg/gCr; P < 0.05). The sensitivity and negative predictive value of beta(2)-MG at the cut-off value at 10.0 x 10(4) microg/gCr (0.90 and 0.92) were comparable to IL-6 at 16 pg/mL (0.90 and 0.94). CONCLUSION: We suggest that measuring urinary beta(2)-MG in premature infants soon after birth can monitor FIRS and may provide information on the risk of subsequent CLD development that is as clinically important as information derived from umbilical cord blood IL-6.

Interleukin-6, interleukin-8, and soluble tumor necrosis factor receptor-I in the cord blood as predictors of chronic lung disease in premature infants.

OBJECTIVES: In order to predict the late-development of chronic lung disease of prematurity (CLD), cytokines in the cord blood were assessed in this study. STUDY DESIGN: Eighteen premature infants with CLD were enrolled. Cord blood plasma levels of cytokines of these infants and 12 control infants without CLD were measured including interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, soluble TNF receptor-I, and soluble IL-6 receptor using a cytometric bead array and an enzyme-linked immunosorbent assay. RESULTS: The cord blood IL-6, IL-8, and sTNFR-I levels were significantly elevated in CLD infants compared with those in control (P < .05). IL-1beta, IL-2, IL-4, IL-10, and IFN-gamma were undetectable in both groups. CLD infants with maternal chorioamnionitis had higher IL-6 than those without chorioamnionitis (P < .01). In CLD infants, IL-6 was higher in the infants who required prolonged oxygen therapy (P < .05). CONCLUSION: Elevated inflammatory cytokines in the cord blood are associated with the progression to CLD.

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.