Firmino F. Rubaltelli

Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants: A prospective double-blind study

Background: It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units (NICUs). The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections (UTIs), bacterial sepsis and necrotizing enterocolitis (NEC) in preterm infants. Methods: A double-blind study was conducted in 12 Italian NICUs. Newborn infants with a gestational age <33 weeks or birthweight <1,500 g were randomized to receive standard milk feed supplemented with Lactobacillus GG (Dicoflor®, Dicofarm, Rome, Italy) in a dose of 6 × 109 colony-forming units (cfu) once a day until discharge, starting with the first feed or placebo. Results: Five hundred eighty-five patients were studied. The probiotics group (n = 295) and the placebo group (n = 290) exhibited similar clinical characteristics. The duration of Lactobacillus GG and placebo supplementation was 47.3 ± 26.0 and 48.2 ± 24.3 days, respectively. Although UTIs (3.4 vs. 5.8%) and NEC (1.4 vs. 2.7%) were found less frequently in the probiotic group compared to the control group, these differences were not significant. Bacterial sepsis was more frequent in the probiotics group (4.4%, n = 11) than in the placebo group (3.8%, n = 9), but the difference was not significant. Conclusion: Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs, NEC and sepsis in preterm infants. Further studies are required to confirm our results in lower birthweight populations.

The role of blood transfusions and iron intake on retinopathy of prematurity

BACKGROUND The role of blood transfusions and iron intake in the pathogenesis or retinopathy of prematurity (ROP) is controversial. AIM To evaluate the influence of packed red cell (PRC) transfusions and iron intake on ROP incidence. STUDY DESIGN Prospective observational study. SUBJECTS Forty-five preterm infants with birthweight <1250 g were studied. After ophthalmological study, they were divided into group A (n=24) that included newborns without ROP, and group B (n=21) that included newborns with ROP. RESULTS Logistic regression analysis demonstrated that gestational age (OR 0.61; 95% C.I. 0.41-0.90), transfusion volume during the first week (OR 1.16; 95% C.I. 1.03-1.3) and during the first 2 months of life (OR 2.93; 95% C.I. 1.52-5.62), and iron intake during the first week of life (OR 1.15; C.I. 1.01-1.32) and during the first 2 months of life (OR 2.93; 95% C.I. 1.52-5.62) were associated with the development of ROP. CONCLUSION Our study showed that gestational age, blood transfusion volume and iron load by transfusions are associated with the risk of occurrence of ROP in infants with a birthweight of less than 1250 g.

Intestinal flora in breast- and bottle-fed infants

We verified whether an adapted formula, which presents poly-oligosaccharides containing maltose, promotes intestinal implantation of bacterial microflora to the extent that breast milk does, as an epidemiological link exists between newborn feeding methods and infant health. Stool specimens were taken and cultured at the fourth day of life from vaginally born neonates. Twenty-two were breast-fed and 20 were fed with formula. In breast-fed infants, the Bifidobacterium was significantly prevalent expressed in percentage (47.6% vs 15%) and in mean bacterial fecal counts/g (7.1 +/- 0.8 vs 5.3 +/- 0.6). Enterococci prevailed in formula-fed infants (mean counts 6.7 +/- 0.9 vs 7.4 +/- 0.5). Of interest is the significant and simultaneous presence of Bifidobacteria and Bacteroides in breast-fed infants. Our study indicates that flora with a diet-dependent pattern is present from the fourth day of life. These results support a preference for breast feeding over formula feeding, even though renewed.

Acute neonatal respiratory distress in Italy: a one-year prospective study

A prospective multicentre 12‐month survey of neonatal respiratory disorders in 63 537 Italian infants was performed to evaluate the incidence of acute neonatal respiratory disorders and of the main related complications. A total of 1427 developed respiratory disorders (2.2%), 208 of whom died (14.6%). The incidence of respiratory distress syndrome was 1.16%, with a case fatality rate (CFR) of 24%; that of transient tachypnoea was 0.93%, with a CFR of 1.3%. The rates of meconium aspiration syndrome, persistent pulmonary hypertension and pneumonia were 0.06%, 0.02% and 0.07%, with CFRs of 10.3%, 38.5% and 21.7%, respectively. The occurrences of the main complications in affected newborns were: bronchopulmonary dysplasia 5.6%, necrotizing enterocolitis 1.7%, patent ductus arteriosus 9.8%, 3o and 4o grade intraventricular haemorrhage 6.8% and air leak 4.9%. It was concluded that the incidence of acute neonatal respiratory disorders and the main related complications was lower than that reported two decades ago and that the CFR of acute neonatal respiratory disorders had increased. These results may be the consequences of (i) progress in the management of high‐risk pregnancies, (ii) an increased number of viable infants with extremely low birth weight and (iii) diffusion of antenatal treatment with corticosteroids which, in this series, seemed to reduce the morbidity but not the mortality in the high‐risk infants.

Epidemiology of Neonatal Acute Respiratory Disorders

A prospective 3-month survey of neonatal respiratory disorders in 17,192 Italian infants born in 65 hospitals, located in 17 Italian regions representative of northern, central and southern Italy, was performed to evaluate the incidence of neonatal acute respiratory disorders and their risk factors. The prematurity rate was 7.3%, while the extremely low birth weight (<1,000 g) and very low birth weight (<1,500 g) rates were 0.58% and 0.99%, respectively. Four hundred and ninety-one infants (2.8%) developed respiratory signs. Lethality or specific fatality rate (SFR) for acute respiratory disorders with regard to the overall study population was 0.45%. The male/female ratio of affected infants was 1.3:1. Among affected newborns the case fatality rate (CFR) for respiratory disorders was 15.88% (78/491) and was higher in males than in females (2:1), in infants with a gestational age of ≤28 weeks (60%) and birth weights of <1,000 g (50%). Moreover, the SFR was higher (p < 0.05) in the infants of mothers older than 34 years. SFR was 3.0% in intrauterine growth-retarded infants, 3.6% in the first twin and 3.2% in the second twin. An Apgar score of ≤3 at 5 min was strongly related to the incidence of respiratory disorders (47.1%). The antenatal prevention of neonatal respiratory distress syndrome with maternal corticosteroid treatment was performed in 84% of newborns (<32 weeks) with respiratory problems in northern Italy, and about 25% and 38% in central and southern Italy, respectively. The CFR was double in southern Italy as compared with northern and central Italy. Prematurity, low birth weight and a low Apgar score (≤3) at 1 and 5 min as well as a maternal age of >34 years are risk factors for acute respiratory disorders.

Prophylaxis of patent ductus arteriosus with ibuprofen in preterm infants

The aim of our study was to evaluate whether the prophylactic use of ibuprofen would reduce the incidence of significant patent ductus arteriosus (PDA) and to confirm the effectiveness of ibuprofen as rescue treatment in closing PDA. Eighty preterm infants with gestational age less than 34 wk with infant respiratory distress syndrome (iRDS) were randomized to receive intravenous ibuprofen lysine (10 mg/kg, followed by 5 mg/kg after 24 and 48 h) either within 24 h of life (group A) or after echocardiographic diagnosis of PDA (group B). To evaluate the severity of RDS in each patient, we calculated the initial and highest values of Oxygenation Index (O.I. =mean airway pressure × FiO2 × 100 / PaO2) and Ventilatory Index (V.I. = O.I. × mechanical respiratory rate). Other studied variables were ventilatory support, renal function, biochemical and haematological profiles, frequency of bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). On the 3rd day of life, 8% (3/40) of patients of group A and 53% of patients (21/40) of group B (p < 0.0001) developed a significant PDA. Between patients of group B who presented PDA at 3 d of life 90% (19/21) had a closure of ductus arteriosus after ibuprofen treatment. Initial and highest values of O.I. and V.I. were similar in both groups A and B. No significant differences between the groups were observed in regard to respiratory support, renal function and frequency of BPD, IVH, NEC and ROP. Ibuprofen was not associated with adverse effects.

Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiency

We used a system capable of measuring conjugated bilirubin and its monoconjugated and diconjugated fractions in serum to assess bilirubin conjugation in 29 glucose-6-phosphate dehydrogenase (G6PD)-deficient, term, male newborn infants and 35 control subjects; all had serum bilirubin levels > or = 256 mumol/L (15 mg/dI). The median value for diconjugated bilirubin was lower in the G6PD-deficient neonates than in control subjects (0.06 (range 0.00 to 1.84) vs 0.21 (range 0.00 to 1.02) mumol/L, p = 0.006). Diglucuronide was undetectable in 11 (38.9%) of the G6PD-deficient infants versus 3 (8.6%) of the control subjects (p = 0.015). These findings imply a partial defect of bilirubin conjugation not previously demonstrated in G6PD-deficient newborn infants.

Maternal education and the incidence and duration of breast feeding: A prospective study

Introduction Duration of breast feeding and factors possibly affecting duration were studied in a population of 2174 newborn infants, with gestational age of >37 weeks, who were born in the Department of Obstetrics and Gynaecology at the University of Florence Hospital between November 15, 1997, and November 14, 1998. Patients and Methods Nine hundred mothers agreed to participate in the study. Five questionnaires were completed at the end of the 1st, 3rd, 6th, 9th, and 12th postpartum month. These dealt with infant feeding practices, including breast feeding during the previous week. Breast feeding duration was defined as short (1 month); medium-short (>1 month–<3 months); medium (>3–<6 months); medium-long (>6–<9 months), and long (>9 months). Results The authors found that 76.3%, 64.7%, 42.3%, 26.4%, and 17% of mothers were still breast feeding at 1, 3, 6, 9, and 12 months after delivery, respectively. The multivariate analysis of the correspondence shows that lack of breast feeding is associated with a birth weight of less than 3000 g, a low level of maternal education, and maternal profession as a housewife or blue collar worker in the commercial sector. A period of breast feeding defined as short or medium-short is associated with mothers who smoke, primiparous mothers, and absence of maternal allergy. The survival curves highlight how the single factor of smoking is an element that leads to a significant difference in the duration of breast feeding. The multiple Cox regression analysis shows a significant negative influence associated with birth weight of less than 3000 g, maternal smoking, and first parity. Above all, among low–birth-weight infants of mothers who smoke, there is a strong correlation with a shorter duration of breast feeding. Discussion There is still a need for programs that support and encourage breast feeding, focusing particularly on mothers with a low level of education who give birth to a low-weight infant, primiparous mothers, and smokers.

Neonatal bilirubin production-conjugation imbalance: Effect of glucose-6-phosphate dehydrogenase deficiency and borderline prematurity

Objective: To evaluate relations between production and conjugation of bilirubin in the pathophysiology of jaundice in glucose-6-phosophate dehydrogenase (G6PD) deficient neonates. Methods: Term and borderline premature (35–37 weeks gestational age), healthy, male, G6PD deficient neonates were studied close to the beginning of the 3rd day. Blood carboxyhaemogobin corrected for inspired CO (COHbc; an index of bilirubin production) and serum total conjugated bilirubin (TCB; a reflection of bilirubin conjugation) were measured in simultaneously drawn blood samples by gas chromatography and reverse phase high performance liquid chromatography respectively. A bilirubin production-conjugation index comprising COHbc/TCB was determined; a high index reflects imbalance between the bilirubin production and conjugation processes. COHbc and TCB individually and the production-conjugation index were studied in relation to serum total bilirubin (STB) concentration. Results: Fifty one G6PD deficient neonates were sampled at 51 (8) hours. COHbc values did not correlate with STB (r  =  0.22, p  =  0.15). TCB did correlate inversely with STB (r  =  −0.42, p  =  0.004), and there was a positive correlation between the production-conjugation index and STB (r  =  0.45, p  =  0.002). The production-conjugation index (median (interquartile range)) was higher in the premature (n  =  8) than term neonates (2.31 (2.12–3.08) v 1.05 (0.53–1.81), p  =  0.003). This difference was the result of changes in TCB. Conclusions: The data show that jaundice in G6PD deficient neonates is the result of an imbalance between production and conjugation of bilirubin with a tendency for inefficient bilirubin conjugation over increased haemolysis in its pathogenesis. Borderline premature infants are at especial risk of bilirubin production-conjugation imbalance.

Plasma bilirubin level and oxidative stress in preterm infants

Objective: To assess the hypothesis that changes in plasma total bilirubin levels (Btot) can influence the antioxidant system and oxidative stress in preterm infants. Methods: Twenty two healthy preterm infants who presented with visible non-haemolytic hyperbilirubinaemia were studied at the mean (SD) age of 3.7 (1.5) days. Btot, plasma total hydroperoxide concentration (TH), plasma protein SH group concentration, and total antioxidant capacity of the plasma (TAC) were measured at study entry and after 24 hours. Results: Btot did not correlate with TH, TAC, or protein SH group concentration, but a significant correlation was found between TH and TAC, TH and protein SH groups, and TAC and protein SH groups, both at study entry and after 24 hours. Conclusion: The decrease in plasma bilirubin was contemporary with an increase in plasma antioxidant capacity and decrease in oxidative stress in preterm infants. This may be the result of the pro-oxidant effect of haem oxygenase, mediated by iron release, which may outcompete the antioxidant properties of bilirubin.