Giorgio Rondini

Intravenous gammaglobulin therapy for prophylaxis of infection in high-risk neonates

The safety and effectiveness of intravenously administered gammaglobulin therapy for prophylaxis of infection was evaluated in 133 high-risk neonates. The infants were stratified into two groups: infants with birth weight less than or equal to 1500 g and gestational age less than or equal to 34 weeks, and infants with birth weight greater than 1500 g and receiving intensive care and assisted ventilation. Forty-three infants in group 1 and 25 in group 2 were given gammaglobulin at a dose of 0.5 g/kg/wk, for 1 month in group 1 and during intensive care in group 2. Forty infants in group 1 and 25 in group 2 served as controls. Serum total IgG and group B streptococcus-, Escherichia coli-, and CMV-specific IgG levels similar to those in adult controls were observed in the treated infants 2 hours after gammaglobulin administration. In the treated infants in group 1, the incidence of infection was 51%, and of septicemia 5%; in the controls the incidence of infection was 77% (P less than 0.02), and of septicemia 20% (P less than 0.05). Infection was the main cause of death in one treated and six control infants in group 1 (P less than 0.04). In the infants with birth weight greater than 1500 g receiving intensive care and assisted ventilation, no significant differences were observed in the incidence of infection or septicemia in treated and control infants. No side effects were observed after intravenous gammaglobulin administration. These data show that intravenously administered gammaglobulin is both safe and effective for prophylaxis of infection in preterm very low birth weight infants.

Age-related changes in intracellular TH1/TH2 cytokine production, immunoproliferative T lymphocyte response and natural killer cell activity in newborns, children and adults.

To evaluate the development of the neonatal immune system, we measured T lymphocyte response to Con A, intracellular IL-2, IL-4, IFN-γ and IL-10 production, and natural killer cell (NKC) activity in 12 very preterm, 12 preterm and 20 term neonates, 10 children and 10 adults. Immunoproliferation to Con A was significantly lower in cord blood than in children or adults. The percentage of CD4+ lymphocytes was significantly higher in newborns while CD8+ cells were higher at older ages, with a resulting gradual decline of the CD4+/CD8+ ratio. The percentage of IL-2-producing CD4+ and CD8+ cells was higher in all newborn groups than in children and adults, while the percentage of IL-4-producing cells was higher for CD8+ and lower for CD4+ cells in cord blood than in children and adults. Neonates had substantially lower percentages of CD4+ and CD8+ IFN-γ-producing cells. A significant negative correlation was observed between gestational age and IFN-γ-CD4+-, IL-2-CD8+-, and IL-10- CD4+-producing cells. In addition, a positive correlation was found between gestational age and IL-10-CD8+-producing cells. Percentages of CD4+/CD45RA+ cells were higher and CD4+/CD45RO+ percentages were lower in newborns than in children and adults. NKC activity in infants was significantly correlated with gestational age and significantly impaired compared to children and adults. On the whole, these results suggest a gradual development of immunity during gestation and show significant immaturity of cellular immune response at birth. The reduction of NKC activity, the lower proliferative response of T cells, the reduced cytotoxic response and a dysregulated cytokine production may contribute to the neonatal increased risk of infection and to the low incidence of graft-versus-host disease after cord blood transplantation.

Activity of Classical and Alternative Pathways of Complement in Preterm and Small for Gestational Age Infants

Summary: Complement activity was compared in 50 low birth weight infants divided into appropriate and small for gestational age groups; the influence of birth weight and gestational age on complement development was also investigated. CH50 and kinetics (tH50) of both classical and alternative pathway activity of complement, C3, and Factor B levels were significantly higher in small for gestational age infants (classical pathway CH50, 630 HU/ml ± 184 SD; CP tH50, 77 min ± 47; aternative pathway CH50, 44.8 HU/ml ±11.3; AP tH50, 56 min ± 43; C3, 73.98 mg/dl ± 12.68; and Factor B, 13.17 mg/dl ± 3.67) than in weight-matched appropriate for gestational age infants (CP CH50, 523 HU/ml ± 152; CP tH50, 105 min ± 49; AP CH50, 38.8 HU/ml ± 13; AP tHs50, 90 min ± 53; C3, 58.14 mg/dl + 9.43; and Factor B, 9.32 mg/dl ± 1.73). Complement values were lower in low birth weight infants than in adult controls (P < 0.001 in all cases). All complement parameters were mainly correlated with gestational age; CH50 values of the classical and alternative pathways were also highly correlated with each other (r= 0.64; P < 0.001).Low birth weight infants, especially preterm infants, have an important defect of complement activity. Complement factors increase gradually during gestation and intrauterine growth retardation does not affect complement development. Classical and alternative complement pathway activities have a similar development pattern.

Family study of non-responsiveness to hepatitis B vaccine confirms the importance of HLA class III C4A locus.

Non-responsiveness to hepatitis B virus (HBV) vaccine in adults is strongly associated with HLA-C4AQ0,DRB1*0301,DQB1*02 haplotype. This association was also demonstrated in neonates who failed to mount a humoral response to challenge with HBV vaccine. About 4% of vaccinated newborns do not reach a protective antibody level (⩾10 mIU/ml) at seroconversion and 0.4% is a non-responder even after receiving a fourth dose of vaccine (true non-responders (TNR)); while 3.6% achieved an antibody level ⩾10 mIU/ml (slow responders (SR)) only when reboostered with the fourth dose. In the present study we extend the vaccination and HLA typing to 91 family members of probands to understand better the possible parent-to-child transmission of this trait. A transmission disequilibrium test (TDT), performed in 27 families, showed that the C4AQ0 allele was almost always transmitted to probands, both TNRs and SRs. Although not statistically significant, the highest LOD score was obtained with C4A locus: 1.58. These results suggest the presence of a region regulating immune response against HBV vaccination near to or coincident with the C4A locus.

Immunogenicity of hepatitis B vaccine in term and preterm infants

Some studies have suggested that decreased seroconversion rates might be found in premature infants with low birthweight (< 2000 g) following administration of hepatitis B vaccine at birth. The aim of the present investigation was to evaluate possible differences in seropositive rates between full‐term and preterm infants after primary vaccination, in particular when gestational age or birthweight is very low. Two‐thousand and nine neonates born to HBs Ag‐negative mothers were vaccinated with 10 μg of recombinant hepatitis B virus (HBV) vaccine, from May 1991 to October 1994. Children with infections, congenital malformations or serious illnesses were excluded. HBV vaccine was administered intramuscularly, on the fourth day of life and again at 1 and 6 months of age. A 1‐ml blood sample was drawn from each infant 1 month after the third vaccine dose for determination of the level of anti‐HBs antibody. The response to HBV vaccination was evaluated in 241 preterm (gestational age < 38 weeks) infants and 1727 term neonates. No statistical difference was observed in the distribution of anti‐HBs antibody level, either between preterm infants (< 38 weeks) and newborns of normal gestational age, or between low birthweight (< 2500 g) and normal weight infants. The results suggest that preterm and low birthweight infants (< 2500 g) respond to HBV vaccine in the same measure as normal‐term infants.

Leukocyte Counts in Relation to the Method of Delivery during the First Five Days of Life

The goal of the present study was to evaluate total and differential leukocyte counts during the first 5 days of life in relation to the method of delivery. We included 203 healthy term infants; of these, 114 were born by vaginal delivery, and 89 by elective cesarean section. Total and differential leukocyte counts were evaluated at the following intervals: 0–6, 7–12, 13–24, 25–48, 49–72, 73–96, and 97–120 h after birth. The cord serum cortisol level was measured as an indicator of the degree of delivery-related stress. Mean leukocyte and neutrophil counts were higher in infants born by vaginal delivery in cord blood and up to 12 h of life. No significant differences were observed in the immature: total neutrophil ratios between the two groups of infants. The cord serum cortisol level was higher in vaginally delivered infants. A significant correlation was found between cortisol and leukocyte, neutrophil, or lymphocyte counts. The method of delivery produces significantly different total leukocyte and neutrophil counts during the first 12 h after birth; after this time, there appears to be no more variation of leukocyte counts during the first 5 days of life.

Different maturation of neutrophil chemotaxis in term and preterm newborn infants

N EW BORN I N FAN TS are known to be particularly susceptible to bacterial infections1-2; the preterm infant is even more susceptible than the term neonate? Impairment of neutrophil functions (chemotaxis, chemolumineseence production, hexose monophosphate shunt activity, and intracellular microbicidal activity) has been found in healthy and stressed newborn infants and related to the susceptibility to infections in these subjects. .6 Miller 4 has suggested that defective neutrophil chemotaxis is one of the main causes of frequent neonatal infections, and this finding has been confirmed by in vivo data. 7 Laurenti et al s have reported that the defect of chemotaxis in preterm infants is similar to that in normal neonates. Up to now, however, only cross-sectional data are available and no longitudinal Studies have been Carried out. The purpose of the present study was to establish the duration of the defect in term and preterm infants.

Effect of Lidocaine on Neutrophil Chemotaxis in Newborn Infants

Anesthetic drugs can influence the immune system, particularly granulocyte function. The goal of the present study was to evaluate if lidocaine used for epidural anesthesia during cesarean section can influence neonatal neutrophil chemotaxis. We measured chemotaxis and plasma cord lidocaine and cortisol levels in (A) 15 infants born by cesarean section with epidural anesthesia, (B) 15 infants born by vaginal delivery, and (C) 20 infants born by cesarean section with general anesthesia. Chemotaxis levels were significantly lower in group A infants (35.5 ± 16.1 μm) compared to groups B (54.6 ± 10.5 μm) and C (71.4 ± 23 μm). The highest cortisol levels were observed in vaginally delivered infants. A significant inverse relationship was observed between chemotaxis and lidocaine levels (r = −0.6, P = 0.016) in infants born by cesarean section after epidural anesthesia, while no significant correlation was observed between chemotaxis and cortisol level. In conclusion, lidocaine, transferred through the placenta to the fetus during epidural anesthesia, may have an inhibitory effect on chemotaxis.

Neurodevelopmental outcome in very low birth weight infants at 24 months and 5 to 7 years of age: Changing diagnosis

We describe the long-term development of 53 very low birth weight premature infants. The children were divided into 2 groups on the basis of ultrasound scan, and classified as: group I, patients with normal ultrasound scan or with uncomplicated hemorrhage; and group II, patients with complicated hemorrhage or only parenchymal lesions. Minor and major sequelae detected at 2 years of age were compared with those observed at 5 to 7 years. Our study confirms that most severely handicapped children are identified by age 2 years. Minor sequelae are more evident at 5 to 7 years and subjects with good outcome, as expressed by a McCarthy General Cognitive Index score > 80, present a discordant cognitive profile with verbal scores higher than performance scores. Therefore, we emphasize the importance of follow-up of very low birth weight premature infants until school age and stress that neonatal ultrasound scan diagnosis of parenchymal damage represents an important diagnostic tool in terms of both short- and long-term neurodevelopmental outcome.

Neonatal B lymphocyte subpopulations and method of delivery

We studied four groups of healthy term newborn infants: (1) 11 infants born by vaginal delivery; (2) 11 infants born by elective cesarean section; (3) 10 infants born by emergency cesarean section with labor, and (4) 10 infants born by complicated vaginal delivery. Total and differential leukocyte counts, cortisol blood level, and B lymphocyte subpopulations (SmIg, sIgD, sIgM, CD19, CD20, CD21, CD23) were evaluated in cord blood samples from the four infant groups. Furthermore, the Pentothal blood level was measured in infants born by elective cesarean section and in their mothers at delivery. Higher total and differential leukocyte counts and cortisol blood levels were observed in group 1 and 4 infants as compared with group 2 and 3 infants. A significant correlation was observed between cortisol blood level and leukocyte counts. The percentages of positivity to cell surface markers of B lymphocyte subpopulations were significantly higher in infants born by elective cesarean section. A negative significant correlation of thiopentone with sIgM and CD21 was observed. These data indicate a significant influence of method of delivery and of thiopentone on B lymphocyte subpopulations.