Mario De Curtis

Neonatal Anthropometric Charts: The Italian Neonatal Study Compared With Other European Studies

Background and Objective: This was a nationwide prospective study carried out in Italy between 2005 and 2007, involving 34 centers with a neonatal intensive care unit. The study reports the Italian Neonatal Study charts for weight, length, and head circumference of singletons born between 23 and 42 gestational weeks, comparing them with previous Italian data and with the most recent data from European countries. Patients and Methods: Single live born babies with ultrasound assessment of gestational age within the first trimester, and with both parents of Italian origin. Only fetal hydrops and major congenital anomalies diagnosed at birth were excluded. The reference set consists of 22,087 girls and 23,375 boys. Results: At each gestational age, boys are heavier than girls by about 4%. Later-born neonates are heavier than firstborn neonates by about 3%. The effects of sex and birth order on length and head circumference are milder. No differences were observed between babies born in central-north Italy and southern Italy. A large variability emerged among European neonatal charts, resulting in huge differences in the percentage of Italian Neonatal Study neonates below the 10th centile, which is traditionally used to define small-for-gestational-age babies. In the last 2 decades prominent changes in the distribution of birth weight emerged in Italy and in the rest of Europe, in both term and preterm neonates. Conclusions: The existing European neonatal charts, based on more or less recent data, were found to be inappropriate for Italy. Until an international standard is developed, the use of national updated reference charts is recommended.

Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns

Background And Objective: Gastric acidity is a major nonimmune defense mechanism against infections. The objective of this study was to investigate whether ranitidine treatment in very low birth weight (VLBW) infants is associated with an increased risk of infections, necrotizing enterocolitis (NEC), and fatal outcome. Methods: Newborns with birth weight between 401 and 1500 g or gestational age between 24 and 32 weeks, consecutively observed in neonatal intensive care units, were enrolled in a multicenter prospective observational study. The rates of infectious diseases, NEC, and death in enrolled subjects exposed or not to ranitidine were recorded. Results: We evaluated 274 VLBW infants: 91 had taken ranitidine and 183 had not. The main clinical and demographic characteristics did not differ between the 2 groups. Thirty-four (37.4%) of the 91 children exposed to ranitidine and 18 (9.8%) of the 183 not exposed to ranitidine had contracted infections (odds ratio 5.5, 95% confidence interval 2.9–10.4, P < .001). The risk of NEC was 6.6-fold higher in ranitidine-treated VLBW infants (95% confidence interval 1.7–25.0, P = .003) than in control subjects. Mortality rate was significantly higher in newborns receiving ranitidine (9.9% vs 1.6%, P = .003). Conclusions: Ranitidine therapy is associated with an increased risk of infections, NEC, and fatal outcome in VLBW infants. Caution is advocated in the use of this drug in neonatal age.

Feeding preterm infants after hospital discharge : a commentary by the ESPGHAN Committee on Nutrition

ABSTRACT Survival of small premature infants has markedly improved during the last few decades. These infants are discharged from hospital care with body weight below the usual birth weight of healthy term infants. Early nutrition support of preterm infants influences long-term health outcomes. Therefore, the ESPGHAN Committee on Nutrition has reviewed available evidence on feeding preterm infants after hospital discharge. Close monitoring of growth during hospital stay and after discharge is recommended to enable the provision of adequate nutrition support. Measurements of length and head circumference, in addition to weight, must be used to identify those preterm infants with poor growth that may need additional nutrition support. Infants with an appropriate weight for postconceptional age at discharge should be breast-fed when possible. When formula-fed, such infants should be fed regular infant formula with provision of long-chain polyunsaturated fatty acids. Infants discharged with a subnormal weight for postconceptional age are at increased risk of long-term growth failure, and the human milk they consume should be supplemented, for example, with a human milk fortifier to provide an adequate nutrient supply. If formula-fed, such infants should receive special postdischarge formula with high contents of protein, minerals and trace elements as well as an long-chain polyunsaturated fatty acid supply, at least until a postconceptional age of 40 weeks, but possibly until about 52 weeks postconceptional age. Continued growth monitoring is required to adapt feeding choices to the needs of individual infants and to avoid underfeeding or overfeeding.

C reactive protein and procalcitonin: Reference intervals for preterm and term newborns during the early neonatal period

BACKGROUND There is still no study evaluating the influence of gestational age (GA) per se on C reactive protein (CRP) and procalcitonin (PCT) reference intervals. We therefore investigated how length of gestation, age (hours), and prenatal and perinatal variables might influence the levels of CRP and PCT. We also determined 95% age-specific reference intervals for CRP and PCT in healthy preterm and term babies during the early neonatal period. METHODS One blood sample (one observation per neonate) was taken for CRP and PCT from each newborn between birth and the first 4 (for term), or 5 days (for preterm newborns) of life by using a high-sensitive CRP and PCT assays. RESULTS Independently of gender and sampling time, GA had a significantly positive effect on CRP, and a significantly negative effect on PCT. Compared with healthy term babies, healthy preterm babies had a lower and shorter CRP response, and, conversely, an earlier, higher, and longer PCT response. CRP reference intervals were affected by a number of pro-inflammatory risk factors. CONCLUSIONS Age- and GA-specific reference ranges for both CRP and PCT should be taken into account to optimize their use in the diagnosis of early-onset neonatal sepsis.

Weight gain composition in preterm infants with dual energy X-ray absorptiometry.

Whole body composition was investigated using dual energy x-ray absorptiometry in 54 healthy preterm infants, birth weight < 1750 g, who were fed fortified human milk (n = 20) and preterm formula (n = 34) when full enteral feeding was attained and then again 3 wk later at around the time of discharge. Weight gain composition was calculated from the difference between the earlier and later measurement. The minimal detectable changes in whole body composition over time according to the variance of the population (within groups of 20 infants) and the minimal detectable changes according to the dietary intervention (between two groups of 20 infants) were determined at 5% significance and 80% power. Whole body composition was similar in the two groups at the initial measurement, but all the measured variables differed at the time of the second measurement. Formula-fed infants showed a greater weight gain (19.9 ± 3.2 versus 15.9 ± 2.2 g·kg-1·d-1, p < 0.05), fat mass deposition (5.1 ± 1.9 versus 3.3 ± 1.3 g·kg-1·d-1, p < 0.05), bone mineral content gain (289 ± 99 versus 214 ± 64 mg·kg-1·d-1, p < 0.05), and increase in bone area (1.6 ± 0.4 versus 1.3 ± 0.3 cm2·kg-1·d-1, p < 0.05) compared with the fortified human milk group. From these data, a minimal increase from the first measurement of 111 g lean body mass, 68 g fat mass, and 3.1 g bone mineral content is needed to be detectable in a longitudinal study that includes 20 infants. For significance between two groups of 20 infants around the time of discharge, dietary intervention needs to achieve minimal differences of 160 g lean body mass, 86 g fat mass, and 4.1 g bone mineral content. With respect to weight gain composition, the minimal differences required to reach significance are 2.1 g·kg-1·d-1 for gain in lean body mass, 1.2 g·kg-1·d-1 for gain in fat mass, and 76 mg·kg-1·d-1 for gain in bone mineral content. We conclude that dual energy x-ray absorptiometry allows evaluation of the effects of dietary intervention on whole body and weight gain composition in preterm infants during the first weeks of life.

Neonatal Onset Intestinal Failure: An Italian Multicenter Study

OBJECTIVE To describe the natural course of intestinal failure with onset in the neonatal period to provide data regarding the occurrence and to provide a population-based survey regarding the spectrum of underlying diseases. STUDY DESIGN We performed a retrospective chart review including infants admitted to the neonatal intensive care unit of 7 Italian tertiary care centers. Intestinal failure was defined as a primary intestinal disease that induces the need of total parenteral nutrition (PN) for more than 4 weeks or the need of partial PN for more than 3 months. RESULTS The total number of live births during the study time within the enrolled institutions was 30 353, and the number of newborns admitted to the neonatal intensive care unit was 5088. Twenty-six patients satisfied the definition of intestinal failure; thus the occurrence rate of intestinal failure was 0.1% among live-birth newborns and 0.5% among infants at high risk. The main underlying diseases leading to intestinal failure in neonatal age were congenital intestinal defects (42.3%), necrotizing enterocolitis (30.8%), severe intestinal motility disorder (11.5%), intestinal obstruction (7.7%), structural enterocyte defects (3.8%), and meconium peritonitis (3.8%). After a follow-up of 36 months, 84.6% of patients achieved intestinal competence, 1 patient was still receiving home PN, 1 patient underwent transplantation, and 2 patients died. Cholestatic liver disease was diagnosed in 54% of observed children. CONCLUSION An understanding of the incidence, causes, and natural history of intestinal failure would be helpful to appropriately allocate resources and to plan clinical trials.

Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis

Objectives We performed a systematic review and meta-analysis of all the available evidence to assess the efficacy and safety of paracetamol for the treatment of patent ductus arteriosus (PDA) in neonates, and to explore the effects of clinical variables on the risk of closure. Data source MEDLINE, Scopus and ISI Web of Knowledge databases, using the following medical subject headings and terms: paracetamol, acetaminophen and patent ductus arteriosus. Electronic and manual screening of conference abstracts from international meetings of relevant organisations. Manual search of the reference lists of all eligible articles. Study selection Studies comparing paracetamol versus ibuprofen, indomethacin, placebo or no intervention for the treatment of PDA. Data extraction Data regarding efficacy and safety were collected and analysed. Results Sixteen studies were included: 2 randomised controlled trials (RCTs) and 14 uncontrolled studies. Quality of selected studies is poor. A meta-analysis of RCTs does not demonstrate any difference in the risk of ductal closure (Mantel–Haenszel model, RR 1.07, 95% CI 0.87 to 1.33 and RR 1.03, 95% CI 0.92 to 1.16, after 3 and 6 days of treatment, respectively). Proportion meta-analysis of uncontrolled studies demonstrates a pooled ductal closure rate of 49% (95% CI 29% to 69%) and 76% (95% CI 61% to 88%) after 3 and 6 days of treatment with paracetamol, respectively. Safety profiles of paracetamol and ibuprofen are similar. Conclusions Efficacy and safety of paracetamol appear to be comparable with those of ibuprofen. These results should be interpreted with caution, taking into account the non-optimal quality of the studies analysed and the limited number of neonates treated with paracetamol so far.

Update in Pathogenesis and Prospective in Treatment of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is among the most common and devastating diseases in neonates and, despite the significant advances in neonatal clinical and basic science investigations, its etiology is largely understood, specific treatment strategies are lacking, and morbidity and mortality remain high. Improvements in the understanding of pathogenesis of NEC may have therapeutic consequences. Pharmacologic inhibition of toll-like receptor signaling, the use of novel nutritional strategies, and microflora modulation may represent novel promising approaches to the prevention and treatment of NEC. This review, starting from the recent acquisitions in the pathogenic mechanisms of NEC, focuses on current and possible therapeutic perspectives.

Zinc supplementation reduces morbidity and mortality in very-low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country

BACKGROUND Zinc plays a pivotal role in the pathogenesis of many diseases and in body growth. Preterm neonates have high zinc requirements. OBJECTIVE The objective of the study was to investigate the efficacy of zinc supplementation in reducing morbidity and mortality in preterm neonates and to promote growth. DESIGN This was a prospective, double-blind, randomized controlled study of very-low-birth-weight preterm neonates randomly allocated on the seventh day of life to receive (zinc group) or not receive (control group) oral zinc supplementation. Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and from 1.3 to 1.4 mg/d in the placebo control group. The main endpoint was the rate of neonates with ≥ 1 of the following morbidities: late-onset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leucomalacia, and retinopathy of prematurity. Secondary outcomes were mortality and body growth. RESULTS We enrolled 97 neonates in the zinc group and 96 in the control group. Morbidities were significantly lower in the zinc group (26.8% compared with 41.7%; P = 0.030). The occurrence of necrotizing enterocolitis was significantly higher in the control group (6.3% compared with 0%; P = 0.014). Mortality risk was higher in the placebo control group (RR: 2.37; 95% CI: 1.08, 5.18; P = 0.006). Daily weight gain was similar in the zinc (18.2 ± 5.6 g · kg⁻¹ · d⁻¹) and control (17.0 ± 8.7 g · kg⁻¹ · d⁻¹) groups (P = 0.478). CONCLUSION Oral zinc supplementation given at high doses reduces morbidities and mortality in preterm neonates. This trial was registered in the Australian New Zealand Clinical Trial Register as ACTRN12612000823875.

Necrotising Enterocolitis in Very Low Birth Weight Infants in Italy: Incidence and Non-nutritional Risk Factors

Incidence and non-nutritional risk factors were estimated for necrotising enterocolitis in 2035 very low birth weight infants, admitted to 14 tertiary-level neonatal intensive care units in Lombardy, northern Italy. There were 62 necrotising enterocolitis cases, with an overall incidence of 3.1%. After adjustment for gestational age and centre, the risk factors were mechanical ventilation, patent ductus arteriosus, and late-onset sepsis, whereas surfactant treatment was associated with decreased risk. Significant variations in necrotising enterocolitis incidence among hospitals were found.