Relationship between Cardiofemoral Index and the plasma concentration of brain natriuretic peptide in anemic fetuses associated with Rh alloimmunization

Background  Fetal anemia is a common result of alloimunization and is an important cause of fetal congestive heart failure resulting in heart dilation. Fetuses suspected of having heart failure present a higher Cardiofemoral Index and an increase in plasma BNP levels, because the cardiac hormonal system is activated by increased heart wall stretch due to increased left ventricular volume and pressure overload. Methods  Our group studied 33 pregnant women (22–31 weeks’ gestation at the first cordocentesis) referred for intrauterine fetal transfusion due to severe red blood cells isoimmunization. Up to 6 h prior to each cordocentesis, all fetuses were submitted to ultrasonography measurements where the Cardiofemoral Index was calculated. Samples of blood from the umbilical vein were collected for hemoglobin concentration and blood gas measurements. Plasma levels of BNP were determined with the use of plasma that had previously been frozen and thawed once. Plasma BNP was measured by radioimmunoassay. Pearson’s correlation test and regression analysis were used to determine the association between the plasma concentration of BNP and the Cardiofemoral Index of the anemic fetuses with RH alloimmunization. Results  Anemia was severe in 17 (50%) fetuses, mild in 9 (26.47%) and in 8 patients (23.53%) the fetuses were not anemic; hemoglobin ranged from 3.10 to 15.70 g/dl. The Cardiofemoral Index ranged from 0.43 to 0.87 and it was altered (≥0.59) in 23 fetuses. A significant positive correlation was observed between BNP plasma fetal concentration and Cardiofemoral Index (Pearson r = 0.61, P < 0.0001). Conclusions  These results suggest that fetal plasma concentration of BNP may increase in fetuses with heart dilation leading to a positive association between Cardiofemoral Index and plasma concentration of BNP. An erratum to this article can be found at     

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.     

Amniotic fluid interleukin-6 and neutrophil gelatinase-associated lipocalin for predicting fetal inflammatory response syndrome based on histological chorioamnionitis and funisitis

ObjectiveWe aimed to analyze the predictive efficacy of amniotic fluid interleukin-6 (IL-6) and neutrophil gelatinase-associated lipocalin (NGAL) for fetal inflammatory response syndrome (FIRS)-related infection.Materials and methodsWe included singleton pregnancies classified into FIRS and non-FIRS groups. FIRS was defined as histologic chorioamnionitis and funisitis. Amniotic fluid samples were collected during vaginal delivery (VD) or cesarean section (CS). We compared amniotic fluid IL-6 and NGAL levels between the groups.ResultsForty-six pregnancies were analyzed and classified into 20 (43.5%) FIRS and 26 (56.5%) non-FIRS pregnancies. We observed significant differences in amniotic fluid IL-6 and NGAL. Amniotic fluid collection significantly influenced NGAL levels (p < 0.001). The area under the concentration–time curve (AUC), with optimal cutoff values, for amniotic fluid IL-6 and NGAL (VD and CS) levels was 0.948 (11,344 pg/mL), 0.800 (1180 ng/mL), and 0.946 (708 ng/mL), respectively.ConclusionAmniotic fluid IL-6 and NGAL levels showed equivalent predictive ability for FIRS-related infection.     

Low-mannose-binding lectin levels in susceptibility to neonatal sepsis in preterm neonates with fetal inflammatory response syndrome

Aim.?In this study, we aimed to evaluate cord blood mannose binding levels (MBL), to evaluate possible relationship between cord blood MBL levels with neonatal sepsis and culture confirmed neonatal sepsis in preterm newborn with gestational age below 34 weeks with fetal inflammatory response syndrome (FIRS).

Methods.?Forty-four randomly selected ≤34 weeks gestational age newborns with FIRS were evaluated. MBL deficiency was described as cord blood levels were below 400?ng/ml.

Results.?Mean value of umbilical cord MBL was significantly lower in newborns with culture confirmed sepsis (p?<?0.01) and also all cases with sepsis (including culture negative or positive) (p?<?0.05) than newborns without sepsis. Culture-confirmed sepsis was statistically common in MBL deficient premature newborns with FIRS. Univariate analysis showed that gestational age, birth weight, low serum MBL level and poor obstetric history were all significantly associated with the risk of neonatal sepsis. A subsequent multivariate analysis showed that the association between serum MBL level and the risk of suspected sepsis and culture confirmed sepsis independently from gestational age and birth weight.

Conclusion.?Here in, we report firstly lower MBL levels were found related with sepsis in neonates, especially in newborns with culture proven sepsis. Low MBL levels may help to identify neonates with FIRS at high risk of developing sepsis.     

An elevated maternal serum C-reactive protein in the context of intra-amniotic inflammation is an indicator that the development of amnionitis,an intense fetal and AF inflammatory response are likely in patients with preterm labor: clinical implications

Abstracts

Objective: We propose that an elevated maternal serum C-reactive protein (CRP) concentration in the context of intra-amniotic inflammation (IAI) is a predictor for amnionitis development, known to be the most advanced stage of maternal inflammatory response during the progression of acute histologic chorioamnionitis in preterm gestations.

Methods: Study population consisted of 53 singleton gestations with IAI, who underwent amniocentesis due to preterm labor and intact membranes (PTL) and delivered preterm-neonates (<34.5 weeks) within 5?days of amniocentesis. The frequency of amnionitis and the intensity of fetal and amniotic fluid (AF) inflammatory response were examined according to the presence or absence of an elevated maternal serum CRP (≥0.7?mg/dL) at the time of amniocentesis. IAI was defined as an elevated AF matrix metalloproteinase-8 (MMP-8) (≥23?ng/mL), and fetal inflammatory response syndrome (FIRS) defined as an elevated umbilical cord plasma CRP (≥200?ng/mL).

Results: (1) Patients (73.6%, 39/53) with an elevated maternal serum CRP had a significantly higher rate of amnionitis (59.0% versus 7.1%; p?<?0.005), but not funisitis (46.2% versus 28.6%; p?>?0.05), and higher median AF MMP-8 and umbilical cord plasma CRP concentration at birth than patients (26.4%,14/53) without that (AF MMP-8 (ng/mL): 373.1 versus 138.6: p?=?0.05; umbilical cord plasma CRP (ng/mL): 363.4 versus 15.5: p?<?0.05); (2) Multiple logistic regression analysis demonstrated that an elevated maternal serum CRP was a better independent predictor of amnionitis (odds ratio (OR), 12.5: 95% confidence interval (CI), 1.1–141.0; p?<?0.05) than FIRS (OR, 3.6: 95% CI, 0.6–20.2; p?=?0.150) and any other AF tests.

Conclusions: An elevated maternal serum CRP concentration in the context of IAI is an indicator that the development of amnionitis, an intense fetal and AF inflammatory response are likely in patients with PTL.