Division of Neonatology, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, MEB 312C, New Brunswick, NJ 08903-0019, USA.
To assess the relationship between perinatal infection/inflammation as reflected by umbilical vein interleukin-6 (IL-6) levels and the development of periventricular-intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants, we tested the hypothesis that VLBW infants who develop IVH have higher concentrations of IL-6 in an umbilical vein sample compared to infants without IVH. An inception cohort of 69 VLBW infants was followed from birth until discharge or death to determine the development of IVH by serial neuroultrasounds. Umbilical vein IL-6 levels were measured using commercially available ELISA kit (Endogen Laboratories, Woburn, MA) and compared in IVH and control cohorts. Twenty-two (32%) infants developed IVH, including 18 (82%) with grade I or II and 4 (18%) with grade III or IV. One of these infants also developed periventricular leukomalacia. The umbilical vein IL-6 levels were significantly elevated in infants with IVH with median value of 87 pg/ml (25th percentile value 30 pg/ml and 75th percentile value 310 pg/ml) compared with infants without IVH, with a median value of 0 pg/ml (25th percentile value 0 pm/ml and 75th percentile value 4 pg/ml) (P = 0.007). Umbilical vein IL-6 levels are elevated in neonates who subsequently develop IVH.
[Show abstract][Hide abstract] ABSTRACT: A growing body of literature supports the relationship of maternal inflammation with preterm birth and adverse neonatal outcomes, including infection and central nervous system (CNS) dysfunction. Mediators of inflammation, most notably proinflammatory cytokines, have been implicated as having an association with and perhaps playing a causal role in the pathogenesis, leading to adverse neonatal outcomes. Even though the association of cytokines with early adverse neonatal outcomes has been actively pursued as a line of research, there has been little integration of diverse findings across studies. Therefore, the purpose of this systematic review was to appraise and classify empirical evidence from human studies for the association of cytokine levels in blood (serum, plasma, or cells; maternal, cord, or neonatal) with two adverse early outcomes in preterm infants: early infection and increased risk of neurologic damage. The review revealed that the proinflammatory cytokines most frequently linked with sepsis are in the interleukin (IL) 1 family as well as tumor necrosis factor alpha (TNF-alpha) and IL-6. The proinflammatory cytokines most frequently linked to neurologic insult in the reviewed studies were IL-1beta, IL-6, and IL-8. In all cases where IL-1beta was studied, the levels were increased when there was neurologic insult. A better understanding of the relationship of these inflammatory substances with these adverse conditions is needed for the future development of maternal and neonatal biobehavioral nursing research.
Biological Research for Nursing 12/2009; 11(4):377-86. DOI:10.1177/1099800409344619 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mortality rate from sepsis is high and the risk of sepsis increases in prematurity in proportion to the decrease in birth weight.
The authors report the assessment of serum interleukin-6 levels in 12 term, at-risk newborn infants after birth and 60 VLBW neonates after detection of non-specific signs of infection or sepsis, treated in NICU at the Semmelweis University, 1st Department of Obstetrics and Gynecology in 2005-2006. The serum IL-6 level with a rapid test (Milenia Quickline IL-6 and PicoScan system) was investigated. The simultaneous assessment of C-reactive protein levels was analysed as well.
The assessment of serum interleukin-6 and CRP levels for the early diagnosis of sepsis can be established or ruled out. The sensitivity of serum IL-6 level assessment was 100%. There were no false negative cases. The positive predictive value was 93%. There was a significant difference between the sepsis and infection group of VLBW infants in the serum Il-6 levels ( p = 0.048), and between the infection and non-infection groups in the interleukin-6 levels ( p < 0.005).
In comparing the diagnostic value of IL-6 measurement in VLBW infants with signs of infection to the diagnostic methods currently in use, results showed that a combination of early assessment of IL-6 and CRP seems to increase diagnostic accuracy in attempting to differentiate between septic and nonseptic patients. Such increased accuracy will decrease neonatal morbidity as well as the financial cost of treatment.
Orvosi Hetilap 08/2007; 148(34):1609-14. DOI:10.1556/OH.2007.27991
[Show abstract][Hide abstract] ABSTRACT: Elevated concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloproteinase-9 (MMP-9) in fetal and neonatal compartments have been associated with an increased risk for preterm birth (PTB) and/or neonatal morbidity. The purpose of this study was to determine if the maternal serum concentration of IL-6, CRP, and MMP-9 in women at risk for PTB, who are not in labor and have intact membranes, are associated with an increased risk for PTB <32 weeks and/or neonatal morbidity. Maternal serum samples collected from 475 patients enrolled in a multicenter randomized controlled trial of single versus weekly corticosteroids for women at increased risk for preterm delivery were assayed. Serum was collected at randomization (24 to 32 weeks' gestation). Maternal serum concentrations of IL-6, CRP, and MMP-9 were subsequently determined using enzyme-linked immunoassays. Multivariate logistic regression analysis was performed to explore the relationship between maternal serum concentrations of IL-6, CRP, and MMP-9 and PTB <32 weeks, respiratory distress syndrome (RDS), chronic lung disease (CLD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and any sepsis. Maternal serum concentrations of IL-6 and CRP, but not MMP-9, above the 90th percentile at the time of randomization were associated with PTB <32 weeks. In contrast, there was no significant relationship between RDS and NEC and the maternal serum concentration of IL-6, CRP, or MMP-9 (univariate analysis). The development of CLD was associated with a high (above 90th percentile) IL-6 and CRP in maternal serum, even after adjustment for gestational age (GA) at randomization and treatment group. However, when GA at delivery was added to the model, this finding was nonsignificant. Neonatal sepsis was more frequent in neonates born to mothers with a high maternal serum concentration of CRP (>90th percentile). However, there was no significant association after adjustment for GA at randomization and treatment group. Logistic regression analysis for each analyte indicated that high maternal serum concentrations of IL-6 and CRP, but not MMP-9, were associated with an increased risk of IVH (odds ratio [OR] 4.60, 95% confidence interval [CI] 1.86 to 10.68; OR 4.07, 95% CI 1.63 to 9.50) after adjusting for GA at randomization and treatment group. Most babies (25/30) had grade I IVH. When GA at delivery was included, elevated IL-6 remained significantly associated with IVH (OR 2.77, 95% CI 1.02 to 7.09). An elevated maternal serum concentration of IL-6 and CRP are risk factors for PTB <32 weeks and subsequent development of neonatal IVH. An elevated maternal serum IL-6 appears to confer additional risk for IVH even after adjusting for GA at delivery.
American Journal of Perinatology 03/2010; 27(8):631-40. DOI:10.1055/s-0030-1249366 · 1.91 Impact Factor
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