The red cell distribution width (RDW): value and role in preterm, IUGR (intrauterine growth restricted), full-term infants.

To measure the red cell distribution width (RDW) ranges at birth and to evaluate potential association with typical neonatal diseases: patent of the ductus arteriousus (PDA), bronchopulmonary dysplasia (BPD), and late-onset sepsis (LOS) mortality.Forty-six full-term, 41 preterm, and 35 intrauterine growth restricted (IUGR) infants participated in this retrospective, observational study. RDW was measured before 3 days of life (T0) in all infants, and at first month of life (T1) in preterm/IURG patients.RDW% mean (standard deviation) at T0 was: 15.65 (1.18) in full-term newborns; 17.7 (2.06) in preterm; 17.45 (1.81) in IUGR. A negative correlation (r = -0.51; P0.001) between RDW and gestational age was found. RDW at T1 was: 17.25 (2.19) in the preterm group; 17.37 (2.56) in IUGR group. Fourteen preterm infants reported: 12 PDA, 5 LOS, 4 BPD, and 3 died; 10 IUGR infants had: 4 PDA, 6 LOS, 3 BPD, and 1 died. RDW of IUGR infants suffering from those pathologies was not statistically different compared with unaffected infants, while preterm newborns with pathologies reported higher RDW: PDA vs. PDA absent: P = 0.008 at T0; P0.002 at T1. BPD vs. BPD absent: P0.005 at T1. LOS vs. LOS absent: P0.005 at T0. RDW in preterm/IUGR population was associated with early mortality, T0: dead 21.2 (2.7) vs. alive 16.7 (1.7), P0.0001.RDW and gestational age at birth were negatively correlated. High RDW resulted to be an indication of risk for critical newborns. This parameter can be inexpensively and routinely verified and further studies are required to confirm its prognostic role in neonatal pathologies

Fetal human cytomegalovirus transmission correlates with delayed maternal antibodies to gH/gL/pUL128-130-131 complex during primary infection

Primary human cytomegalovirus (HCMV) infections during pregnancy are associated with a high risk of virus transmission to the fetus. To identify correlates of intrauterine HCMV transmission, serial serum samples from HCMV transmitter and non-transmitter pregnant women with primary HCMV infection were analyzed for the presence of neutralizing antibodies against different glycoproteins and glycoprotein complexes, which are known to mediate entry into distinct types of host cells. Neutralizing activity was detected in the sera early after primary infection; absorption with a soluble pentameric complex formed by gH/gL/pUL128-131, but not with gH/gL dimer or with gB, abolished the capacity of sera to neutralize infection of epithelial cells. Importantly, an early, high antibody response to pentamer antigenic sites was associated with a significantly reduced risk of HCMV transmission to the fetus. This association is consistent with the high in vitro inhibition of HCMV infection of epithelial/endothelial cells as well as cell- to-cell spreading and virus transfer to leukocytes by anti-pentamer antibodies. Taken together, these findings indicate that the HCMV pentamer complex is a major target of the antibody-mediated maternal immunity

The red cell distribution width (RDW): Value and role in preterm, IUGR (intrauterine growth restricted), full-term infants

To measure the red cell distribution width (RDW) ranges at birth and to evaluate potential association with typical neonatal diseases: patent of the ductus arteriousus (PDA), bronchopulmonary dysplasia (BPD), and late-onset sepsis (LOS) mortality.Forty-six full-term, 41 preterm, and 35 intrauterine growth restricted (IUGR) infants participated in this retrospective, observational study. RDW was measured before 3 days of life (T0) in all infants, and at first month of life (T1) in preterm/IURG patients.RDW% mean (standard deviation) at T0 was: 15.65 (1.18) in full-term newborns; 17.7 (2.06) in preterm; 17.45 (1.81) in IUGR. A negative correlation (r = -0.51; P0.001) between RDW and gestational age was found. RDW at T1 was: 17.25 (2.19) in the preterm group; 17.37 (2.56) in IUGR group. Fourteen preterm infants reported: 12 PDA, 5 LOS, 4 BPD, and 3 died; 10 IUGR infants had: 4 PDA, 6 LOS, 3 BPD, and 1 died. RDW of IUGR infants suffering from those pathologies was not statistically different compared with unaffected infants, while preterm newborns with pathologies reported higher RDW: PDA vs. PDA absent: P = 0.008 at T0; P0.002 at T1. BPD vs. BPD absent: P0.005 at T1. LOS vs. LOS absent: P0.005 at T0. RDW in preterm/IUGR population was associated with early mortality, T0: dead 21.2 (2.7) vs. alive 16.7 (1.7), P0.0001.RDW and gestational age at birth were negatively correlated. High RDW resulted to be an indication of risk for critical newborns. This parameter can be inexpensively and routinely verified and further studies are required to confirm its prognostic role in neonatal pathologies

Fetal Human Cytomegalovirus Transmission Correlates with Delayed Maternal Antibodies to gH/gL/pUL128-130-131 Complex during Primary Infection

<div><p>Primary human cytomegalovirus (HCMV) infections during pregnancy are associated with a high risk of virus transmission to the fetus. To identify correlates of intrauterine HCMV transmission, serial serum samples from HCMV transmitter and non-transmitter pregnant women with primary HCMV infection were analyzed for the presence of neutralizing antibodies against different glycoproteins and glycoprotein complexes, which are known to mediate entry into distinct types of host cells. Neutralizing activity was detected in the sera early after primary infection; absorption with a soluble pentameric complex formed by gH/gL/pUL128-131, but not with gH/gL dimer or with gB, abolished the capacity of sera to neutralize infection of epithelial cells. Importantly, an early, high antibody response to pentamer antigenic sites was associated with a significantly reduced risk of HCMV transmission to the fetus. This association is consistent with the high <i>in vitro</i> inhibition of HCMV infection of epithelial/endothelial cells as well as cell-to-cell spreading and virus transfer to leukocytes by anti-pentamer antibodies. Taken together, these findings indicate that the HCMV pentamer complex is a major target of the antibody-mediated maternal immunity.</p> </div

IgG antibody titers and DNA viral load at three time points of primary HCMV infection.

<p>IgG antibody titers in 11 non-transmitter (NT) and 12 transmitter (T) mothers against gB (A), gH/gL (B), or pentamer (C) at three different time intervals (≤30 days, 30–60 days, >60 days) after onset of infection. (D) HCMV DNA copies/ml blood in the same sera samples at the three time intervals. Dotted lines represent the detection limit of the assays. <i>P</i>-values were calculated using the Mann-Whitney U-test (A-C) or the Fisher’s exact test (D).</p

Kinetics of the antibody response to primary HCMV infection.

<p>(A) Kinetics of the appearance of anti-pentamer (IgG-Pent), anti-gH/gL (IgG-gH/gL) and anti-gB (IgG-gB) antibodies in 46 subjects with primary HCMV infection. Shown are individual values and non-linear regression curves for the three specificities. <i>P</i>-values were calculated using the extra-sum-of square F test. (B) Kinetics of the mean HCMV serological response in the 46 patients’ sera. IgG-HCMV refers to HCMV lysate-specific IgG Arbitrary Units (AU); IgM-HCMV refers to HCMV lysate-specific IgM ratio; Nt-HELF and Nt-ARPE19 refer to neutralizing antibody (Neut Ab) titer on human embryonic lung fibroblasts (HELF) and epithelial (ARPE-19) cells, respectively; HCMV DNA refers to viral load in blood. (C) Correlation between IgG-pentamer antibody titers measured by ELISA and neutralizing antibody titers measured using ARPE-19. Values were obtained from sera collected <60 day post infection (filled diamonds) or >60 days post infection (empty diamonds). The regression coefficient (r²) is also shown. (D) Neutralizing antibody (Neut Ab) titers of sera from 3 patients (Pt.A, Pt.B, and Pt.C) were measured using ARPE-19. Sera were used either untreated or after absorption with the soluble pentameric complex, gH/gL dimer, or gB proteins from HCMV or with influenza A virus hemagglutinin (HA).</p

Effect of serum absorption with purified HCMV proteins on ELISA IgG antibody titer.

a<p>Influenza A hemagglutinin.</p

SDS-PAGE and Western blot (WB) analysis of soluble HCMV glycoprotein complexes.

<p>(A) Pentameric gH/gL/pUL128-131 complex, (B) gH/gL and (C) gB complexes were subjected to SDS-PAGE and Western blotting. Samples were stained with Coomassie blue (left panels) or probed with specific antibodies after WB (right panels). (B) A band of about 60 kDa on gL blot is apparently a co-purified contaminant recognized by anti-gL polyclonal serum raised in rabbits. (C) Soluble gB exists in full-length and truncated forms that associate in dimeric complex, as described in Carlson et al. (32). N-terminus of truncated gB form is not detected since gB was his-tagged on the C-terminus and the blot was probed with anti-histag antibody.</p

Cumulative antibody response to the pentamer neutralization sites.

<p>Patients’ antibody response to neutralizing sites of the pentamer estimated <i>via</i> inhibition of monoclonal antibody binding (IMAB) assay using a panel of 10 human monoclonal antibodies with defined specificity for different sites on the HCMV pentamer complex, as indicated. The cumulative incidence of site-specific antibodies in 23 pregnant women with primary HCMV infection during the entire follow-up period is shown.</p