Maternal serum interleukin-6 and its association with clinicopathological infectious morbidity in preterm premature rupture of membranes: a prospective cohort study

Objective: To analyze the association of maternal serum interleukin-6 (IL-6) with fetomaternal outcome in preterm premature rupture of membranes (PPROM). Methods: Serial serum IL-6 levels were measured in 45 women with PPROM at gestation 24–34 weeks. The women were followed till pueperium and fetomaternal outcome as well as the histopathology of the placenta and the umblical cord was studied. The data were analyzed using t test and χ² test. Results: IL-6 levels ≥ 8 pg/ml were significantly associated with puerperal sepsis and neonatal sepsis. Histological chorioamnionitis and funisitis were demonstrated in 48.8% and 13.3% women respectively and significantly correlated with elevated serum IL-6 levels and fetomaternal infection. A cut-off value of IL-6 of 8 pg/ml was found to correctly diagnose 19 out of 23 patients with infectious morbidity and showed the best sensitivity (82.6%) and specificity (86.3%) as compared to the total leucocycte count (TLC) and C-reactive protein (CRP) in diagnosing infection in PPROM. Conclusion: Maternal serum IL-6 can be used as a biomarker to predict preclinical asymptomatic infection in PPROM with good sensitivity and specificity.     

Differences in the fetal interleukin-6 response to microbial invasion of the amniotic cavity between term and preterm gestation

Background/objective: Fetal inflammatory response has been implicated as a mechanism of multi-system organ injury in preterm and term neonates. Microbial invasion of the amniotic cavity (MIAC) is frequently associated with a fetal inflammatory response. However, there are no studies comparing the fetal response to MIAC in term and preterm gestations. The purpose of this study was to compare the umbilical cord plasma interleukin-6 (IL-6) concentrations in term and preterm neonates in the presence or absence of MIAC. Study design: Umbilical cord blood was obtained at birth from 252 neonates whose mothers had an amniocentesis within 48 h of delivery (preterm delivery, n = 62; term delivery, n = 190). MIAC was defined as a positive amniotic fluid culture for bacteria or genital mycoplasmas. IL-6 was measured by a sensitive and specific immunoassay. Results: The median IL-6 concentration in umbilical cord plasma was significantly higher in preterm neonates than in term neonates (median 13.4 pg/ml, range 0.1-676 pg/ml vs. median 3.2 pg/ml, range 0.1-408 pg/ml; p < 0.0001). In the context of MIAC, the median umbilical cord plasma IL-6 concentration was significantly higher in preterm than in term neonates (median 31.6 pg/ml, range 1.4-676 pg/ml vs. median 11.7 pg/ml, range 1.3-82 pg/ml, respectively; p < 0.05). Neonates born to mothers with a positive amniotic fluid culture had a significantly higher median IL-6 concentration than neonates born to mothers with a negative amniotic fluid culture (preterm: median 31.6, range 1.4-676 pg/ml vs. median 8.0, range 0.1-656 pg/ml; p < 0.05 and term: median 11.7, range 1.3-82 pg/ml vs. median 3.1, range 0.1-408 pg/ml; p < 0.01, respectively). Conclusions: The preterm fetus is capable of mounting a systemic cytokine response as measured by IL-6 in its peripheral blood. In the setting of MIAC, a fetal IL-6 response is higher in preterm than in term gestation.     

Evidence for fetal involvement in the pathologic process of clinical chorioamnionitis

OBJECTIVE: Clinical and histologic chorioamnionitis have recently been identified as risk factors for cerebral palsy. Proinflammatory cytokines have been implicated in the mechanisms that are responsible for brain injury in cases of intrauterine infection. The purpose of this study was to determine whether clinical chorioamnionitis, which is a maternal syndrome, is associated with an elevation in the fetal plasma interleukin-6 (IL-6) that is indicative of fetal inflammation. STUDY DESIGN: A cross-sectional study was designed to determine plasma concentrations of IL-6 in umbilical venous blood from patients with clinical chorioamnionitis (n = 26) and a control group (n = 111). Umbilical cord blood was obtained at the time of delivery. Plasma concentrations of IL-6 were measured with a sensitive and specific immunoassay. Nonparametric statistics were used for analysis. RESULTS: Plasma concentrations of IL-6 were detectable in all samples of umbilical venous plasma. The median concentration of plasma IL-6 was higher in neonates born to mothers with clinical chorioamnionitis than in neonates born to mothers in the control group (clinical chorioamnionitis: median, 27.46 pg/mL; range, 1.3-5550.0 pg/mL; vs control: median, 2.13 pg/mL; range, 0.6-812.3 pg/mL; P <.001). Sixty-two percent of neonates (16/26) who were born to women with clinical chorioamnionitis had fetal plasma concentrations of IL-6 >11 pg/mL and 54% (14/26) had fetal plasma concentrations of IL-6 >18 pg/mL (these cutoff points have been used previously to define the fetal inflammatory response syndrome). CONCLUSION: Umbilical vein plasma concentrations of interleukin-6 are elevated in the neonates who were born to mothers with clinical chorioamnionitis, which suggests that the inflammatory process that is responsible for the maternal syndrome of clinical chorioamnionitis frequently involves the human fetus.     

Association between funisitis and elevated interleukin-6 in cord blood

OJBECTIVE: To determine whether elevated plasma interleukin-6 (IL-6) in umbilical venous cord blood at delivery is associated with funisitis and whether IL-6 can be used to screen for funisitis in preterm neonates. METHODS: At the time of delivery, umbilical venous cord blood samples were collected from 92 infants for whom placental pathology results were also available. Interleukin-6 concentrations in the umbilical venous cord blood plasma were measured by immunoassay. Histologic examinations of the placenta and umbilical cord were done to determine the presence or absence of funisitis and chorioamnionitis. For a power of 90% with an alpha of.05, 12 subjects were required in each group. RESULTS: We found a significant association between the presence of histologic funisitis and elevated umbilical venous cord blood plasma IL-6 concentrations (defined as 10 pg/mL or greater). Of 15 infants whose umbilical cords showed funisitis, 93% (14 of 15) had elevated umbilical venous cord blood plasma IL-6 concentrations. Of 77 infants without funisitis, 32% (25 of 77) had elevated IL-6 concentrations in their cords (P <.001, two-sided Fisher exact test). The negative predictive value of IL-6 as a screening test for funisitis was 98%. CONCLUSION: In preterm neonates, screening for funisitis by using the immunoassay for IL-6 appears to be valid. In the near future, elevated umbilical venous cord blood IL-6 concentrations at delivery could be clinically useful to identify children who might benefit from early treatment for systemic fetal inflammatory syndrome.     

Maternal chorioamnionitis and umbilical vein interleukin-6 levels for identifying early neonatal sepsis

Objective: The purpose of this study was to determine whether elevated levels of umbilical vein IL-6 would be a better marker for early neonatal sepsis than the clinical signs of maternal chorioamnionitis.

Methods: Patients delivering preterm because of spontaneous preterm labor or premature rupture of the membranes were evaluated for clinical signs of chorioamnionitis, which was defined as a temperature of ≥ 100.4°F along with ≥2 of the following: significant maternal tachycardia (≥120 bpm), fetal tachycardia (≥160 bpm), purulent discharge, uterine tenderness, and leukocytosis (WBC ≥ 18,000 cells/mm³). Umbilical vein blood was assayed for interleukin-6. An elevated interleukin-6 level was determined to be 25 pg/mL. Infants were evaluated for evidence of early neonatal sepsis. The abilities of clinical chorioamnionitis and interleukin-6 levels ≥25 pg/mL to predict early neonatal sepsis were compared.

Results: There were 28 patients delivering 14 (50%) neonates with evidence for early neonatal sepsis. The incidence of suspected neonatal sepsis in women with and without clinical chorioamnionitis was 6/10 (60%) vs. 8/18 (44.4%), P = 0.43. Using receiver operator characteristic curves, the best cutoff for interleukin-6 was found to be 25 pg/mL. The compared sensitivity, specificity, and positive and negative predictive values of clinical chorioamnionitis vs. interleukin-6 levels ≥25 pg/mL for predicting early neonatal sepsis were 42.9% vs. 92.9%, 71.4% vs. 92.9%, 60% vs. 92.9%, and 55.6% vs. 92.9%, respectively.

Conclusions: Elevated umbilical vein levels of interleukin-6 predict those preterm infants with early sepsis better than the presence of clinical chorioamnionitis.     

Maternal venous procalcitonin levels do not correlate with umbilical cord blood and venous blood concentrations in the neonate

BACKGROUND: To compare procalcitonin (PCT) concentrations between maternal blood and levels in umbilical cord or venous blood of neonates who were born with or without infection. METHODS: Forty-six women with singleton pregnancies, complicated by premature rupture of membranes, preterm delivery and/or chorioamnionitis, were enrolled in this study. The study group comprised 15 patients and their infected newborns. The control group consisted of 31 women and their healthy newborns. We compared PCT concentrations between maternal, umbilical cord and neonatal serum, in both study and control groups. Additionally, PCT levels were compared between the corresponding compartments. RESULTS: PCT concentrations in the umbilical cord and venous blood in infected newborns, but not in non-infected neonates, were significantly higher than maternal serum PCT levels. PCT concentrations of mothers who delivered infected newborns were comparable to those in the controls. However, PCT concentrations in the umbilical cord and in the venous blood of the infected newborns were higher than in healthy newborns. CONCLUSION: Measurement of maternal PCT concentration during labor does not contribute to early prediction of infection in the neonate. However, umbilical cord PCT concentrations, as well as its neonatal venous levels on the second day of life, seem to be related to intrauterine infection, and may be a useful tool in the diagnosis of early neonatal infection.     

Assessment of cord blood IL-6 levels as an indicator of neonatal sepsis

Based on the recognition that interleukin-6 (IL-6) is produced early in infection, IL-6 determinations have been used to identify infants with early onset bacterial sepsis. This study intended to assess the value of IL-6 in maternal, cord and infant peripheral blood as an index of sepsis, and examine the relationships of its values in mother and infants. The population consisted of 17 mother/infant pairs at high risk for neonatal infection. Eight of these infants had clinical signs of possible sepsis. Cord blood IL-6 levels in infants of mothers considered to be noninfected were lower than those born to women with chorioamnionitis. There was also a positive correlation between maternal and cord blood IL-6 values. There were no differences in maternal blood IL-6, whether they had infections or not. Also, peripheral infant blood obtained after birth did not differentiate between those born to women with or without chorioamnionitis, nor did it correlate with maternal blood IL-6 levels. Clinical symptoms of the infants did not correlate with either cord or peripheral blood IL-6 values. Although maternal prepartum treatment with antibiotics and/or steroids may influence their own and their infants' blood IL-6 levels, there is insufficient evidence to consider low infant blood IL-6 level a reliable predictor to rule out early newborn sepsis.     

Maternal serum interleukin-6 levels predict impending funisitis in preterm premature rupture of membranes after completion of antibiotics

Objective: To determine if maternal serum interleukin-6 (IL-6) levels remain predictive of funisitis after completion of antibiotic administration in preterm premature rupture of membranes (PPROM). Methods: A secondary analysis of a prospective cohort study. Daily blood samples obtained from PPROM subjects were analyzed for IL-6 by enzyme-linked immunosorbent assay. Subjects (N?=?39) delivered >7days post admission and were divided into those with and without funisitis. Data were analyzed using Mann–Whitney U test. Results: Maternal serum IL-6 levels obtained 24–48 hours and 48–72 hours before delivery are elevated in PPROM subjects with funisitis compared to those without funisitis (6.3 vs. 2.7 pg/ml, P?<?0.03; 6.1 vs. 1.7 pg/ml, P?<?0.02). Receiver operator characteristic curve revealed an IL-6 level of 1.98 pg/ml had sensitivity of 86.7%, specificity of 46.7%, positive predictive value of 61.9% and negative predictive value of 77.8%. Conclusion: This data suggests that maternal serum IL-6 levels continue to be predictive of PPROM subjects destined to develop funisitis after completion of antibiotics.     

The fetal inflammatory response in subgroups of women with preterm prelabor rupture of the membranes

Abstract

Objective: To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on the intensity of the fetal inflammatory response and the occurrence of fetal inflammatory response syndrome (FIRS) in preterm prelabor rupture of membranes (PPROM).

Methods: One hundred and forty-nine women with singleton pregnancies complicated by PPROM between the gestational ages 24?+?0 and 36?+?6 weeks were included in the study. Blood samples were obtained by venipuncture from the umbilical cord after the delivery of the newborn. The umbilical cord blood interleukin (IL)-6 levels were evaluated using ELISA kits. The fetal inflammatory response was determined by IL-6 levels, and FIRS was defined as an umbilical cord blood IL-6 >11?pg/mL.

Result: IL-6 levels and the occurrence of FIRS were higher in women complicated with both MIAC and HCA (median IL-6 35.5?pg/mL, FIRS in 68%) than in women with HCA alone (median IL-6 5.8?pg/mL, FIRS in 36%), MIAC alone (median IL-6 2.8?pg/mL, FIRS in 17%) or women without MIAC or HCA (median IL-6 4.3?pg/mL, FIRS in 29%). There were no differences in IL-6 levels or rates of FIRS among women with MIAC alone or HCA alone and women without both MIAC and HCA.

Conclusion: A higher fetal inflammatory response mediated by umbilical cord blood IL-6 was identified when both MIAC and HCA were detected in pregnancies complicated by PPROM.     

Umbilical blood gas analysis in preeclamptic versus healthy pregnancies with preterm birth

Objective: Comparing the value of umbilical cord arterial blood gas (UC-ABG) analysis in the prediction of neonatal mortality and morbidity in the preeclamptic versus healthy pregnancies with preterm birth.

Methods: Eight hundred sixteen preterm (born at?<37 gestational weeks) neonates with no other morbidities who were born by cesarean section were evaluated. Immediately after delivery, UC-ABG analysis was performed and the neonates were followed.

Results: Preeclamptic women had lower umbilical cord blood (UCB) pH (7.2 4?±?0.1 versus 7.2 7?±?0.08, p?=?0.008) and higher UCB base deficit (BD) (3.5?±?3.7 versus 2.2?±?3.4, p?=?0.005) compared with controls. In the preeclamptic group, UCB metabolic acidosis (pH?<?7.15 and B.D?>?8) was not independently associated with neonatal morbidity or mortality, while in the control group UCB metabolic acidosis was independently associated with low 10-min Apgar (OR, 4.9; 95%CI 1.37–18.03), respiratory distress syndrome (OR, 2.37; 95%CI 1.05–6.17), intraventricular hemorrhage (OR, 3.01; 95%CI 1.13–7.99), and neonatal mortality (OR, 17.33; 95%CI 4.51–66.53).

Conclusions: The preterm neonates born to preeclamptic mothers have lower UCB pH and higher BD. In these neonates, UCB acidosis is not independently associated with any adverse neonatal outcomes. In contrast, in the preterm neonates born to healthy mothers, UCB metabolic acidosis is independently associated with neonatal mortality and morbidity.     

Intraamniotic inflammation and umbilical cord blood interleukin-6 concentrations in pregnancies complicated by preterm prelabor rupture of membranes

Objective: To evaluate umbilical cord blood interleukin (IL)-6 concentrations and the occurrence of fetal inflammatory response syndrome (FIRS) with respect to microbial invasion of the amniotic cavity (MIAC) and/or intraamniotic inflammation (IAI) in pregnancies complicated by preterm prelabor rupture of membranes (PPROM).

Methods: One-hundred-eighty-eight women with singleton pregnancies complicated by PPROM between gestational ages of 24?+?0 and 36?+?6 weeks were included in the study. Blood samples were obtained by venipuncture from the umbilical cord after the delivery of the newborn. The umbilical cord blood IL-6 concentrations were evaluated using ELISA kits. FIRS was defined as umbilical cord blood IL-6?>?11?pg/mL.

Result: Women with MIAC and IAI had higher IL-6 concentrations than women without these complications (with MIAC: median 18.1?pg/mL versus without MIAC: median 5.8; p?<?0.0001; with IAI: median 32.9?pg/mL, versus without IAI: median 5.8; p?<?0.0001). Women with IAI with MIAC and women with IAI without MIAC had the highest umbilical cord blood IL-6 concentrations (medians: 32.6 and 39.4?pg/mL) and rates of FIRS (78% and 67%).

Conclusions: IAI was associated with the highest umbilical cord blood IL-6 concentrations and rate of FIRS independent of the presence or absence of MIAC.     

The relationship between sonographic fetal thymus size and the components of the systemic fetal inflammatory response syndrome in women with preterm prelabour rupture of membranes

Objective  To assess the relation between sonographic fetal thymus size and the components of fetal inflammatory response syndrome (FIRS) in women with preterm prelabour rupture of membranes (PPROM).
Design  Prospective cohort study.
Setting  University hospital from January through October 2006.
Population  Fifty-six women with PPROM.
Methods  In these women, fetal thymus perimeter was measured sonographically. At birth, cord venous plasma interleukin-6 (IL-6) level estimation and histopathological examination of the placentas and umbilical cords were performed.
Main outcome measures  Small thymus size (<5th percentile for gestational age) and its association with FIRS.
Results  From the 56 women with PPROM, 54% had chorioamnionitis (CA), 23% had funisitis. IL-6 level was >11 pg/ml in 52% of women and >18 pg/ml in 41%. A small thymus was more associated with male fetuses, shorter preterm prelabour rupture of membranes delivery interval, higher IL-6 level, higher frequency of funisitis and CA. When data were regressed for confounding, only IL-6 level and funisitis remained significant independent factors that influence the thymus size. In the subset of women ( n = 19) who delivered within 1 week of first measurements, a small thymus had sensitivity and positive predictive value of 93%, specificity and negative predictive value of 75% and accuracy of 89% in the identification of FIRS (IL-6 >18 pg/ml and/or funisitis).
Conclusions  An association exists between fetal thymic involution and components of FIRS in women with PPROM. Small fetal thymus size may be considered a reliable sonographic marker of fetal involvement in the inflammatory response.     

Umbilical cord plasma interleukin-6 concentrations in preterm infants and risk of neonatal morbidity

OBJECTIVE: This study was undertaken to evaluate the association between umbilical cord interleukin-6 (IL-6) levels and neonatal morbidity in infants born at less than 32 weeks' gestation. STUDY DESIGN: Umbilical cord plasma IL-6 levels and neonatal outcomes were assessed in 309 infants born between 24 weeks and 0 days' and 31 weeks and 6 days' gestation. RESULTS: Mean IL-6 levels were higher in spontaneous (n = 193, 355 +/- 1822 pg/mL) compared with indicated preterm births (n = 116, 37 +/- 223 pg/mL, P < .0001). Adjusting for gestational age, a progressive relationship was noted between increasing IL-6 levels and increased risk of neonatal systemic inflammatory response syndrome (SIRS). IL-6 levels beyond the 90th percentile (> or =516.6 pg/mL) were also significantly associated with periventricular leukomalacia (PVL; odds ratio [OR] 15, 95% CI 2-149) and necrotizing enterocolitis (NEC; OR 6, 95% CI 1.1-33). In the multivariate analysis, an IL-6 level 107.7 pg/mL or greater (determined by receiver operating curve analysis) remained a significant independent risk factor for PVL (OR 30.3, 95% CI 4.5-203.6). CONCLUSION: Umbilical cord IL-6 levels are higher in preterm infants born after spontaneous preterm labor or premature rupture of membranes. Elevated IL-6 levels are associated with an increased risk for SIRS, PVL, and NEC in infants born at less than 32 weeks' gestation.     

Maternal plasma interleukin-6, interleukin-1beta and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery.

OBJECTIVE: To investigate whether maternal serum interleukin-6 (IL-6), interleukin-1beta (IL-1beta) and high sensitive C-reactive protein (CRP) could be used as markers of tocolysis failure and adverse neonatal outcome in pregnancies with preterm labor (PL). METHODS: Forty-seven maternal blood samples taken because of PL at admission and delivery were analyzed. Control samples were taken from 20 gravidas with normal pregnancies. Differences in interleukins and CRP levels with or without chorioamnionitis, connatal infection or periventricular leukomalacia (PVL) were analyzed. Cut-off values were estimated for prediction of tocolysis failure and adverse neonatal outcome. RESULTS: All three parameters were significantly higher in patients delivering prematurely than in patients delivering at term. All three parameters were significantly higher with than without histologic chorioamnionitis (p < 0.001), with than without connatal infection (p < 0.01), with than without PVL (p < 0.01 for IL-6 and IL-1beta, p < 0.05 for CRP), and in pregnancies with preterm premature rupture of membranes (PPROM) delivered within 48 hours compared to those more prolonged (p < 0.01). Choosing 50.9 pg/mL of IL-6 and a CRP of 19.7 as cut-offs in maternal blood admission concentrations for neonatal PVL, resulted in sensitivity of 81% and specificity of 91% and sensitivity of 91% and specificity of 81%, respectively. At respective maternal blood admission cut-off levels of 27.8 pg/mL of IL-6 and 8.9 of CRP, both parameters were effective predictors of connatal infection. CONCLUSIONS: Maternal blood IL-6 and CRP could become useful in predicting tocolysis failure and intrauterine treat for the fetus.     

Placental transfer of rubella-specific IgG in fullterm and preterm newborns.

OBJECTIVES: This study was undertaken to investigate placental transfer of anti-rubella IgG immunoglobulins in Iranian mothers. METHODS: In total, 231 pregnant women and their paired infants enrolled in this study of which, 197 gave birth to fullterm and 26 gave birth to preterm infants. Rubella specific antibodies were detected by an in-house whole-virus ELISA assay in maternal and cord sera of 188 fullterm and 26 preterm infants. RESULTS: A highly significant correlation was observed between anti-rubella IgG in newborns in total, in preterm and fullterm neonates with their paired mothers (P-values=0.0001, 0.002, 0.0001, respectively). A borderline significant difference was observed between mean anti-rubella IgG in fullterm and preterm neonates (P=0.04). Mean cord/maternal ratio of anti-rubella IgG was 0.83 which was surprisingly low. A significant lower anti-rubella IgG was observed in newborns born from mothers with blood group B+ than those born from mothers with blood groups A+ (P=0.04) and O+ (P=0.02), respectively. The same difference was observed between mean maternal anti-rubella IgG in those with blood groups B+ and A+ (P=0.04) and those with blood groups B+ and O+ (P=0.05). In addition, a low frequency of B+ blood group in high positive sera and a high frequency of this blood group among low positive and negative sera was detected. CONCLUSIONS: Our data suggest that the main factors that influence the infants' rubella-specific IgG concentration are maternal concentration of this immunoglobulin, maternal blood group, and neonatal gestational age.     

Neonatal thrombocytopenia in the hypertensive disorders of pregnancy

Infants of hypertensive mothers are at risk for a platelet count below 150 x 10(9)/L. To define this risk and assess maternal factors influencing the prevalence of neonatal thrombocytopenia, we collected cord blood samples from 520 infants of 607 consecutive hypertensive mothers with singleton pregnancies. The platelet count in cord blood from infants of hypertensive mothers was compared with that of a control normotensive population, and other comparisons were made among various maternal hypertensive groups. The rate of neonatal thrombocytopenia was 9.2% in hypertensive patients, compared with 2.2% in infants of normotensive mothers (P less than .00001). In the hypertensive group, preterm birth was the major risk factor for neonatal thrombocytopenia. Term infants of hypertensive mothers were no more likely to be thrombocytopenic than were control infants. Only two infants, both preterm, had cord platelet counts below 50 x 10(9)/L. Although obstetric interventions are not indicated, the rate of thrombocytopenia in preterm infants born to hypertensive women justifies neonatal scrutiny.     

Cord blood interleukin-6 and neonatal morbidities among preterm infants with PCR-positive ureaplasma urealyticum

Objectives: To evaluate the clinical significance of Ureaplasma urealyticum recovery from umbilical cord blood, using Polymerase Chain Reaction (PCR), and its association with umbilical cord interleukin-6 (IL-6) levels and neonatal morbidity in preterm infants. Methods: Cord blood PCR for Ureaplasma urealyticum, and IL-6 were assessed in relation to neonatal outcomes of 30 preterm deliveries of less than 35 weeks’ gestation. Results: Ureaplasma urealyticum was present in 43.3% of the examined cord blood samples. Positive neonatal Ureaplasma urealyticum was more common in association with premature rupture of membranes, chorioamnionitis, antenatal maternal use of antibiotics, and earlier gestation. Ureaplasma urealyticum was also associated with an early pro-inflammatory immune response (i.e. elevated IL-6 and positive C-reactive protein). Cutoff level of interleukin-6 of 240 pg% predicts the occurrence of respiratory distress syndrome (RDS), in neonates with positive PCR for Ureaplasma urealyticum. Conclusions: Preterm patients with positive cord blood PCR for Ureaplasma urealyticum were more likely to have premature rupture of membrane, antenatal antibiotics, chorioamnionitis, earlier gestation, pro-inflammatory response, and RDS than those with a negative PCR. High IL-6 is more likely associated with RDS in Ureaplasma urealyticum positive neonates.     

Association of preterm birth with sustained postnatal inflammatory response

OBJECTIVE: To investigate fetal or neonatal inflammatory patterns based on 25 inflammatory markers in neonatal dried blood spots samples from infants born preterm and term, collected several days after birth. METHODS: Dried blood spots samples from 160 neonates were analyzed for 25 inflammatory markers using multiplex technology: 26 neonates born very preterm (before 32 weeks of gestation), drawn at a mean 6 days (95% confidence interval [CI], 5-7 days) after birth; 52 born preterm (32-36 weeks of gestation), drawn at mean 5 days (95% CI, 5-6 days) after birth; and 82 born at term (at or after 37 weeks of gestation), drawn at mean 5 days (95% CI, 5-5 days) after birth. Markers statistically significantly associated with preterm birth were analyzed in a multivariable model together with maternal and neonatal risk factors for preterm birth. RESULTS: Elevated levels of interleukin (IL)-1beta, IL-6, soluble IL-6ralpha, IL-8, matrix metalloproteinase-9, and transforming growth factor-beta1 and decreased levels of IL-18, brain-derived neurotrophic factor, and C-reactive protein were associated with preterm birth. Maternal risk factors could explain only an increase of IL-1beta, whereas neonatal factors could explain several of the elevated and decreased inflammatory markers in the dried blood spots samples from the infants born preterm compared with the infants born at term. CONCLUSION: The differences in levels of inflammatory markers in dried blood spots samples from infants born preterm compared with infants born at term supports the hypothesis that inflammation of fetal origin might be a cause of preterm birth. LEVEL OF EVIDENCE: II.     

Premature infants born after preterm premature rupture of membranes with 24–34 weeks of gestation: a study of factors influencing length of neonatal intensive care unit stay

Objectives.?To determine the factors influencing length of neonatal intensive care unit (NICU) stay among premature infants born after preterm premature rupture of membranes (PPROM) with 24–34 weeks of gestation.

Methods.?Characteristic parameters of the pregnant women with PPROM and their premature infants were analyzed retrospectively using univariate and multivariate analysis.

Results.?The overall rate of PPROM was 1.3% (323/24,173), of which 19.2% (62/323) were premature infants with sepsis. Overall, the median NICU stay of the premature infants was 11 days. Multiple factor regression analysis identified factors influencing length of stay in premature infants: gestational age (β?=??0.172, P?=?0.000), parturition modes (β?=??0.115, P?=?0.000), infant’s birth weight (β?=??0.728, P?=?0.000), infant’s discharge weight (β?=?0.443, P?=?0.000), bacterial culture of cord blood (β?=??0.100, P?=?0.011) and sepsis (β?=?0.192, P?=?0.000). Additionally, latency period of sepsis diagnosis in neonatal sepsis between negative and positive cord blood culture was significantly discrepant, and 98.1% specificity and 84.4% positive predictive value for cord blood culture.

Conclusion.?We have identified several predictive factors for length of stay in cases of premature infants after PPROM, of which cord blood culture can be used as an additional diagnostic test to detect newborns at risk of infections, and be valuable in clinical application and generalization among neonate sepsis.     

Oxidative stress and antioxidant status among neonates born to mothers with pre-eclampsia and their early outcome

Abstract

Objective: To study the oxidative stress and antioxidant status among neonates born to pre-eclamptic mothers and their role in the early outcome of these babies.

Study design: This case control study was conducted at a tertiary care teaching hospital in South India. We included 75 neonates born to mothers with pre-eclampsia matched against 75 neonates born to mothers with normal blood pressure. Relevant antenatal and neonatal clinical data were collected for all babies. Levels of malondialdehyde (MDA) and total antioxidant status (TAS) were estimated in cord blood and oxidative stress was correlated with early neonatal outcome.

Results: Oxidative stress was increased among cases compared to controls as evidenced by increased mean MDA levels (7.43?±?1.21 versus 3.06?±?0.69?µmol/L) and decreased mean TAS (742.15?±?27.30 versus 829.26?±?23.16?mmol/L). Level of oxidative stress correlated with poor neonatal outcome including sepsis, NEC and respiratory distress among cases. An MDA value of 8.68?µmol/L can be used as a cut-off, with sensitivity of 60% and specificity of 89.2%, to predict neonatal death among babies born to pre-eclamptic mothers.

Conclusion: Oxidative stress is increased in neonates born to mothers with pre-eclampsia and useful in predicting outcome.