Prophylactic nasal continuous positive airways pressure in newborns of 28-31 weeks gestation: multicentre randomised controlled clinical trial.

BACKGROUND: The role of nasal continuous positive airways pressure (nCPAP) in the management of respiratory distress syndrome in preterm infants is not completely defined. OBJECTIVE: To evaluate the benefits and risks of prophylactic nCPAP in infants of 28-31 weeks gestation. DESIGN: Multicentre randomised controlled clinical trial. SETTING: Seventeen Italian neonatal intensive care units. PATIENTS: A total of 230 newborns of 28-31 weeks gestation, not intubated in the delivery room and without major malformations, were randomly assigned to prophylactic or rescue nCPAP. INTERVENTIONS: Prophylactic nCPAP was started within 30 minutes of birth, irrespective of oxygen requirement and clinical status. Rescue nCPAP was started when Fio2 requirement was > 0.4, for more than 30 minutes, to maintain transcutaneous oxygen saturation between 93% and 96%. Exogenous surfactant was given when Fio2 requirement was > 0.4 in nCPAP in the presence of radiological signs of respiratory distress syndrome. MAIN OUTCOME MEASURES: Primary end point: need for exogenous surfactant. Secondary end points: need for mechanical ventilation and incidence of air leaks. RESULTS: Surfactant was needed by 22.6% in the prophylaxis group and 21.7% in the rescue group. Mechanical ventilation was required by 12.2% in both the prophylaxis and rescue group. The incidence of air leaks was 2.6% in both groups. More than 80% of both groups had received prenatal steroids. CONCLUSIONS: In newborns of 28-31 weeks gestation, there is no greater benefit in giving prophylactic nCPAP than in starting nCPAP when the oxygen requirement increases to a Fio2 > 0.4.

Iron balance and iron nutrition in infancy.

At birth, the total body iron content is approximately 75 mg/kg, twice that of an adult man in relation to weight. During the first 6 mo of life, total iron body content increases slightly and exclusive breastfeeding is sufficient to maintain an optimal iron balance. Thereafter, iron body content substantially increases and the infant becomes critically dependent on dietary iron, provided by complementary foods. Numerous factors may contribute to nutritional iron deficiency in infancy, the most important being low body iron content at birth, blood loss, high postnatal growth rate, and a low amount and/or bioavailability of dietary iron. We have documented that the prevalence of iron deficiency declined in Italy as iron nutrition improved and that early feeding on fresh cow's milk is the single most important determinant of iron deficiency in infancy. Healthy full-term infants should maintain optimal iron balance by consuming a good diet, which can be summarized as follows: breastfeeding should be continued exclusively for at least 5 mo and then together with complementary foods containing highly bioavailable iron; infants who are not breastfed or are partially breastfed should receive an iron-fortified formula, containing between 4.0 and 8.0 mg/L iron, from birth to 12 mo of age; fresh cow's milk should be avoided before 12 mo of age.

Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity.

This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study. Over a 6-month period (November 1,1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants. Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-positive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age or= 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV+ was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection. The collected data show that, in Italy, RSV is an important cause of lower respiratory tract infection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease.

Neonatal aortic arch thrombosis as a result of congenital cytomegalovirus infection.

Thrombotic disease is rare in neonates. The main risk factors at this age are perinatal asphyxia, maternal diabetes, sepsis, polycythemia, dehydration, a low cardiac output, and in primis the catheterization of central lines. Another important risk factor is inherited thrombophilia. Arterial thrombosis is even more rare than venous thrombosis and less related to most of the risk factors listed above; it occurs more frequently in the iliac, femoral, and cerebral arteries but very rarely in the aorta. Most of the described cases of aortic thrombosis are associated with the catheterization of an umbilical artery and involve the descending tract and the renal arteries; very few relate to the ascending tract and the aortic arch. The possible role of virus-induced primary vascular endothelium damage in the etiopathogenesis of neonatal arterial thrombosis has been previously hypothesized. Herpesviruses, particularly human cytomegalovirus (HCMV), can infect endothelial cells and directly damage intact vascular endothelium, altering its thromboresistant surface as a result of procoagulant activity mediated by specific viral surface phospholipids, necessary for the coagulation enzyme complex assembly that leads to thrombin generation. We describe a case of congenital aortic arch thrombosis. The clinical, laboratory, and virologic pictures; the anatomopathologic findings (fully compatible with viral infection); the detection of HCMV in various tissues (including the aorta); and the absence of other causes of aortic thrombosis make it possible to attribute the case to a severe congenital HCMV infection with multiple organ involvement, after the primary infection of the mother. The hemostatic system disorders and hemodynamic disturbances related to viral cardiac damage explain the clinical features of the case and indicate that congenital HCMV infection should be included among the causes of neonatal aortic thrombosis.

Infants of immigrant parents in Italy. A national multicentre case control study.

BACKGROUND: The aim of this study was to evaluate health state of newborns of immigrated parents from developing countries. METHODS: Hospital records of 69,605 infants born during 1996/1997 in Italy were reviewed comparing, in a case-control study, each infant of immigrated parents to two infants born immediately before and after to Italian parents. RESULTS: Of the 69,605 newborns 3906 (5.6%) were born to immigrated parents. This prevalence prolongs the increasing trend observed during the last 10 years of infants born to immigrated parents and reduces the fall of the birth rate linked to the few infants born to Italian parents. It was influenced by geographical factors, being higher in Northern-Central Italy (7%) than in Southern and Insular Italy (2.8%), as consequence of more elevated incomes in these Italian regions. The origin countries of immigrated parents were mainly Northern Africa (31.7%), Eastern Europe (18%) and Sub Saharan Africa (11.6%). Infants of immigrated parents showed higher incidences of prematurity, low birth weight, asphyxia and neonatal mortality rate than newborns with Italian parents. These higher incidences appeared related to some risk factors such as higher parity, short gestational age, some maternal infections, maternal drug dependence, maternal age less than 18 years, low familiar income, inadequate obstetric cares, difficulty to accessing the public health services. CONCLUSIONS: The health problems of infants with immigrated parents are mainly related to social disadvantage and can be overcome improving the social state, the lifestyles and the obstetric cares of the immigrated women, so as monitoring their risk pregnancies.

Dopamine D4 receptor (DRD4) polymorphism and adaptability trait during infancy: a longitudinal study in 1- to 5-month-old neonates.

We have examined the relationship between the common dopamine D4 receptor (DRD4) exon III repeat polymorphism and infants' behavior measured with the Italian version of the Early and Revised Infancy Temperament Questionnaires (EITQ/RITQ) in 122 Italian neonates at 1 and 5 months of life, when the genetic contribution to the behavior can be more clearly assessed. Two-way (genotype x age) analysis of variance revealed a significant correlation with the temperamental subscale of adaptability [F(1, 120) = 5.26, P < 0.02]. At 1 month of life (early assessment), infants with long (L) DRD4 alleles presented significantly low scores (L 2.61 +/- 0.073; S 2.84 + 0.79; Newman-Keuls P = 0.03) in comparison with the high scores of infants with short (S) alleles (L 2.4 +/- 0.059; S 2.25 +/- 0.57). These differences were not detected at 5 months of life (late assessment), denoting a strong environmental effect at this age on the genetic background. These results confirm and extend the genetic influence of the DRD4 gene in human temperament at birth.

[Neonatal sepsis]. / Le sepsi neonatali.

Sepsis is still one of the most important causes of mortality and morbidity in the neonatal period. Infection is responsible for approximately 2 million neonatal deaths per year in developing countries. In Italy, as in other industrialized countries, the mortality rate has declined to 5.1 per 1000 livebirths. Progress in obstetrics and neonatal intensive care competence have improved survival particularly of preterm and low birth weight neonates. These neonates, for the immunological state and the invasive therapies they are subjected to, are extremely at risk for sepsis. Knowledge of neonatal risk factors, together with cytokines evaluation as early markers of sepsis and laboratory tests such as polymerase chain reaction, have allowed us to accelerate the diagnosis of sepsis with prognostic improvements. The frequent involvement of group B streptococci and coagulase-negative staphylococci requires empiric antibiotic therapy, effective for these pathogens, in all infants with suspected infection, waiting for blood cultures and antibiotic susceptibility results. Breast milk, carrier of immunologically active agents, is still the best prophylaxis for neonatal sepsis.

Breastfeeding duration and current neonatal feeding practices in Emilia Romagna, Italy.

A cohort of 1567 infants was studied at birth and at 3 mo of age to elucidate factors possibly affecting feeding policies in the maternity ward and the relationship with subsequent feeding patterns. During their stay in the maternity wards 89.6% of infants were breastfed, with 28.1% receiving formula in addition to mother's milk. Independent predictors of receiving a formula supplement in the maternity wards as a result of multivariate analyses were the separation of the newborn from the mother, a birthweight lower than 3000 g and a gestational age lower than 38 wk. At 3 mo of age, 66.1% infants were still at least partially breastfed and 48.9% were exclusively breastfed. An increased risk of not being breastfed at 3 mo of age was related to supplementary feeding at birth and birthweight. A weak relationship was found between the prevalence of breastfeeding at 3 mo of age and the magnitude of routine formula supplement use in the maternity ward. Given the present trends for early discharge from maternity wards and the National Health System facility for free paediatric assistance after discharge, in Italy paediatricians should be the main actors to support the continuation of breastfeeding.

Low growth hormone-binding protein in infants with congenital hypothyroidism.

We evaluated the circulating levels of GH, insulin-like growth factor I (IGF-I), GH-binding protein (GHBP), and IGF-binding protein-3 (IGFBP-3) before L-T4 therapy in 19 infants with congenital hypothyroidism (CH), aged 12-29 days, diagnosed by neonatal screening and in a group of age- and sex-matched control infants. The same parameters were reevaluated after several months of treatment. Serum GHBP was measured by the high performance liquid chromatography-gel filtration method; serum GH, IGF-I, and IGFBP-3 levels were determined by commercial kits. The hypothyroid patients, before beginning therapy, presented significantly lower GHBP values than controls (P < 0.0001); during treatment, these values increased significantly; however, after 6 months they were still significantly lower than control values (P < 0.01). The pretreatment levels of GH were not significantly different from control values; after 1 month of treatment, GH did not show the decrease observed in controls and, therefore, was significantly higher (P < 0.01). The pretreatment levels of IGF-I were not significantly different from control values, but were lower in patients with severe than in those with mild hypothyroidism. They decreased at about 4 months of life and became significantly lower than control values at about 7 months of age (P < 0.05). In conclusion, it may be hypothesized that the condition of CH induces a change in GHBP expression, perhaps beginning in fetal life. The intrauterine production of IGF-I seems to be independent of the levels of GHBP and partially affected by fetal thyroid function.

The preterm infant's antibody response to a combined diphtheria, tetanus, acellular pertussis and hepatitis B vaccine.

Several combined vaccines have recently been developed, in order to improve the implementation of immunization programmes and increase the coverage for each vaccine. As the response of preterm infants may vary depending on the vaccination schedule and the vaccine product, it should be evaluated specifically as new vaccines become available. In this study we have examined the antibody response to a combined diphtheria, tetanus, acellular pertussis, and hepatitis B vaccine (DTPa-HBV), given as a primary vaccination course at 3, 5 and 11 months of postnatal age, in 34 preterm infants (mean gestational age (GA) = 32.0 weeks) in comparison with 28 term infants. At the end of the primary course, preterm infants had antibody concentrations for pertussis 69 kDa antigen and diphtheria toxoid that were significantly lower than those of term infants; preterm infants with GA < or = 31 weeks had antibody concentrations for pertussis 69 kDa antigen and HBsAg that were significantly lower than those of preterm infants with higher GA; anti-HBs antibody levels correlated with GA. However, the combined DTPa-HBV vaccine elicited seroconversion to all its components in all but two infants, one term and one preterm, after the second dose and a total seroconversion after the third dose. We conclude that preterm infants may be immunized with a combined DTPa-HBV vaccine, starting at the same chronological age, as term infants.

Prevention of allergies of infants: breast-feeding and special formulas. Influence on the response to immunization.

Infant formulas containing partially hydrolyzed cow milk-proteins are used for the prevention of allergy when maternal milk is not available, and, in preterm infants, also for improving gastric emptying. The nutritional adequacy of such formulas has not yet been completely defined. As the type of feeding may influence the antibody response to immunization, the aim of the present study was to evaluate the antibody response to oral polio virus immunization in term infants and to acellular pertussis and hepatitis B immunization in preterm infants, exclusively fed a partially hydrolyzed cow-milk formula during the first 5 months of life, in comparison with exclusively breast-fed infants. Active immune response occurred in all the infants after the second dose of immunization and no significant difference in the antibody titres was found according to the type of milk. On the basis of these results, it seems that protein nutrition based exclusively on a partially hydrolyzed formula does not impair the response to immunization in both preterm and term infants.

Immunohematological study in newborn infants with erythroblastosis fetalis transfused in utero.

The present study reports immunohematological data (anti-erythrocyte titer, anti-erythrocyte functional activity, percentage of sensitized erythrocytes) in 11 patients with erythroblastosis fetalis transfused in utero (IUTd). At birth it was possible to define two groups of newborns: one with low (group 1) and one with high (group 2) percentage of circulating sensitized erythrocytes, respectively. The presence of a low rate of sensitized red cells at birth in IUTd infants did not reduce the number of exchange transfusions required postnatally. On the contrary, babies of this group were affected by a more severe disease as shown by higher anti-erythrocyte maternal titer, higher anti-erythrocyte functional activity and a higher degree of fetal hemolysis. The persistence of hemolysis after birth, in spite of the absence of sensitized circulating erythrocytes, may be due to intramedullary hemolysis.

Clinical development of a combined diphtheria, tetanus, acellular pertussis, and hepatitis B vaccine in Italy.

In Italy, oral polio vaccine and diphtheria and tetanus (DT) and hepatitis B (HB) vaccinations are required by law. At present, infants receive DT and HB by two separate intramuscular injections during one visit, and most receive an additional injection of acellular pertussis vaccine at the same time. Although simultaneous administration of the vaccines has the advantage of only one medical visit, it is time-consuming for staff, very expensive, painful to the infants, and stressful for parents. A much better solution would be to administer a ready-to-use mixture containing all the vaccines, provided that this combination vaccine had good local and systemic safety profiles and clinical and immunologic efficacy. To evaluate such a combination vaccine in healthy infants at 3, 5, and 11 and at 2, 4, and 6 months of age, a multicenter clinical study is underway in Italy.

Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants.

The influence of dietary long chain polyunsaturated fatty acid (LCP) supply, and especially of docosahexaenoic acid (DHA), on evoked potential maturation, was studied in 58 healthy preterm infants using flash visual evoked potentials (VEPs), flash electroretinography (ERG), and brainstem acoustic evoked potentials (BAEPs) at 52 weeks of postconceptional age. At the same time, the fatty acid composition of red blood cell membranes was examined. The infants were fed on breast milk (n = 12), a preterm formula supplemented with LCP (PF-LCP) (n = 21), or a traditional preterm formula (PF) (n = 25). In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar; in the PF group the morphology was quite different and the wave latencies were significantly longer. This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower. Moreover, a higher level of erythrocyte LCP, especially DHA, was found in breast milk and PF-LCP groups compared with the PF group. ERG and BAEP recordings were the same in all three groups. These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available.

Erythropoietin course in newborns with Rh hemolytic disease transfused and not transfused in utero.

This study reports the Hb, erythropoietin (Epo), and reticulocyte course at different postnatal ages (range, 8-83 d) of 56 blood samples from 30 newborns (range, one or two blood samples from each newborn) with erythroblastosis fetalis (18 intrauterine transfused (IUTd) and 12 non-IUTd). Hb, Epo, and reticulocyte values were not statistically different in IUTd and non-IUTd cases. As age increased, decreasing Hb values and increasing Epo levels were observed. The reticulocyte count was relatively low in all but six cases. There was an inverse correlation between Epo and Hb (r = -55, p < 0.001), but no correlation was found between Hb and reticulocytes or between Epo and reticulocytes. When groups were formed on the basis of Hb levels, anemic newborns showed higher serum Epo than did nonanemic patients (p < 0.02). In the present study we found a significant increase in Epo levels in anemic newborns without a rise in the reticulocyte count. These results suggest that other mechanisms, rather than low Epo production, could be involved in the pathogenesis of this anemia. Persisting anti-D antibodies, probably at a medullary level, may destroy erythrocyte precusors, leading to anemia with a low reticulocyte count.

Iron nutrition and iron status changes in Italian infants in the last decade.

Two groups of 9-15 month old Italian infants were studied, at a 9 years' interval, to evaluate and compare feeding practices and their effect on iron status. Nutritional iron supply has increased in the last decade, due to a larger use of breast milk and iron-fortified infant formulas. In 1983, 21.6% of infants were breast-fed for 5 months or more, compared with 50.6% in 1992. In 1983, 73.3% of infants were fed on fresh cow's milk by the age of 6 months, compared with 7.6% in 1992. Consequently, iron status is markedly improved. In 1983, 5% of the examined infants were anemic and 20.7% showed iron deficiency without anemia, compared with 1.3% and 10.3% respectively in 1992. Our study supports the following recommendations: after 5 months of age exclusively breast-fed infants should receive an additional 1 mg/kg/die iron supplement and iron fortified formulas should be used instead of fresh cow's milk during the first year of life.

Sonography of fetal agenesis of the corpus callosum: a survey of 35 cases.

Agenesis of the corpus callosum was identified by ultrasound examination in 35 fetuses between 19 and 37 weeks' gestation. The ultrasound findings included absence of the corpus callosum and cavum septum pellucidum (hypoplasia in one case of partial agenesis of the corpus callosum), a typical 'teardrop' configuration of the lateral ventricles, distension of the interhemispheric fissure, upward displacement of the third ventricle, radiate arrangement of the medial cerebral gyri, and abnormal branching of the anterior cerebral artery. Associated anomalies were identified in 20 fetuses, including heterogeneous malformations and chromosomal aberrations (mosaic-trisomy 8 in three, trisomy 18 in two and partial duplication 8p in one). Five cases of agenesis of the corpus callosum were identified in a population of pregnant patients prospectively investigated because of genetic risk for agenesis of the corpus callosum or related syndromes. In this group, no diagnostic errors were made. Long-term neurological follow-up (6 months to 11 years) was available in 11 infants with antenatal diagnosis of isolated agenesis of the corpus callosum. Normal intellectual development was present in nine, and a low intellect (developmental quotient between 70 and 85) was found in two. It is concluded that fetal agencies of the corpus callosum is associated with elusive sonographic findings that can, however, be accurately identified by targeted examinations. In routine sonograms, an increased atrial width and/or failure to visualize the cavum septum pellucidum should arise the suspicion of fetal agencies of the corpus callosum. Given the high frequency of associated anomalies, prenatal diagnosis of agencies of the corpus callosum dictates the need for a careful survey of fetal anatomy and karyotyping. The prognosis is isolated agencies of the corpus callosum remains uncertain, although it is expected that a normal or boarderline intellectual development will occur in many cases.