Claudio Martano

Necrotizing enterocolitis: risk factor analysis and role of gastric residuals in very low birth weight infants.

Objective: Necrotizing enterocolitis (NEC) usually occurs in very low birth weight infants and is the most common gastrointestinal emergency in the neonatal intensive care unit. Inasmuch as NEC mortality and morbidity are extremely high, early diagnosis becomes essential. Increased gastric residuals are used to define NEC stage, but studies on qualitative and quantitative residual features as markers of NEC risk are still lacking. The primary goal of this analysis was evaluation of the role of gastric residuals in early identification of patients at risk for NEC. The secondary goal was investigation of NEC risk factors, besides prematurity and birth weight. Methods: In a case-control study, NEC patients were matched with control infants by gestational age and birth weight. Feeding tolerance was assessed by maximum gastric residual volume, maximum residual as percentage of previous feeding, and residual appearance. Mortality and NEC risk factors were also evaluated. Results: In all, 844 very low birth weight infants were admitted to the neonatal intensive care unit during the study period, with an overall mortality before discharge of 14.6%. NEC frequency was 2%. Patent ductus arteriosus was significantly associated with NEC. Mean maximum residual from birth to NEC onset and maximum residual as percentage of the corresponding feed volume were significantly higher in patients than in control infants, as was the percentage of infants with hemorrhagic residuals. Conclusions: Gastric residuals are a marker of feeding intolerance, and bloody residuals seem to be the best predictor for NEC. For early detection of very low birth weight infants at risk for NEC, both gastric residual volumes and bloody residuals represent an early relevant marker.

Benefits of donor milk in the feeding of preterm infants.

Mothers own milk is widely recognized as the optimal feeding for term infants, but also provides health benefits that are of vital importance for sick and preterm infants in neonatal intensive care units (NICUs), even though the growth and neurodevelopmental needs of very premature infants are best met by appropriate fortification of human milk (HM). When mothers milk is unavailable or in short supply, donor milk (DM) represents the second best alternative and, although some nutritional elements are inactivated by the pasteurization process, it still has documented advantages compared to formula. Occasionally, the concern that the use of DM might decrease breastfeeding is being raised, but reports exist in literature showing that the use of donor HM in the NICU increases breastfeeding rates at discharge for VLBW infants. The demonstrated benefits of HM highlight the importance of educating health care professionals in breastfeeding support.

Weight growth velocity of very low birth weight infants: role of gender, gestational age and major morbidities

Its well known that VLBWI fail to thrive, however its still unclear how gender, GA and morbidities affect growth pattern: aim of this study is to assess the influence of these factors on weight growth. 262 VLBWI were selected. Weight was recorded daily up to 28 days, weekly up to discharge and during 7 scheduled follow-up visits up to 2 years of corrected age. Individual profiles were fitted with a mathematical function suitable to model selected growth milestones and mean distance and velocity curves were drawn. Effects of gender, GA, major-morbidities, nutritional and respiratory support on individual weight growth milestones were estimated using a multivariate linear model. Each of these variables acts differently on weight growth pattern mainly modifying velocity curves characteristics. In particular, infants with major morbidities weight growth impairment-seen on distance curves at 2 years of corrected age-depends on poor weight velocity during a critical period ending within 4th month of postnatal age, for SGA or BPD infants, starting from 5th month of postnatal for severely neurologically impaired infants. These critical periods could be the most appropriate to identify risk factors for weight growth impairment in VLBWI.

High-Dose Ibuprofen for Patent Ductus Arteriosus in Extremely Preterm Infants: A Randomized Controlled Study.

Our aim was to assess the hypothesis that a high‐dose regimen of ibuprofen is more effective than the standard‐dose regimen in closing patent ductus arteriosus (PDA) without increasing adverse effects. Infants of gestational age <29 weeks, with respiratory distress syndrome (RDS) and echocardiographic evidence of significant PDA at 12–24 h of life, were randomized to receive a standard (10–5–5 mg/kg/day) or high‐dose (20–10–10 mg/kg/day) course of ibuprofen. We studied 70 infants, 35 of whom received the standard dose of ibuprofen and the other 35 the high dose. Of the infants treated with the standard‐dose regimen, 37% had persistent PDA as compared with 14% of those treated with the high‐dose regimen (P = 0.03). No differences in the occurrence of adverse effects were observed between the two groups. The high‐dose ibuprofen regimen is more effective than the standard‐dose regimen in closing PDA in preterm infants <29 weeks of gestation without increasing the adverse effect rate.

Relationship between maternal- and fetal-specific IgE.

Aim:  A positive correlation between maternal and cord‐blood IgE levels is well documented for total IgEs, but not for specific IgEs. The difficulty in detecting specific cord‐blood IgEs is due to their low concentrations, which hinder their dosage by low‐sensitivity methods. The study aimed to correlate maternal and foetal specific IgEs against individual cows milk proteins, detected by highly sensitive and specific techniques.

Exome sequencing and pathway analysis for identification of genetic variability relevant for bronchopulmonary dysplasia (BPD) in preterm newborns: A pilot study

BACKGROUND Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infancy, affecting preterm children with low birth weight. The disease has a multifactorial aetiology with a significant genetic component; until now published association studies have identified several candidate genes but only few of these data has been replicated. In this pilot study, we approached exome sequencing aimed at identifying non-common variants, which are expected to have a stronger phenotypic effect. MATERIALS AND METHODS We performed this study on 26 Italian severely affected BPD preterm unrelated newborns, homogeneously selected from a large prospective cohort. We used an Illumina HiSeq 2000 for sequencing. Data analysis was focussed on genes previously associated to BPD susceptibility and to new candidates in related pathways, highlighted by a prioritization analysis performed using ToppGene Suite. RESULTS By exome sequencing, we identified 3369 novel variants, with a median of 400 variations per sample. The top candidate genes highlighted were NOS2, MMP1, CRP, LBP and the toll-like receptor (TLR) family. All of them have been confirmed with Sanger sequencing. CONCLUSIONS Potential candidate genes have been discovered in this preliminary study; the pathogenic role of identified variants will need to be confirmed with functional and segregation studies and possibly with further methods, able to evaluate the collective influence of rare variants. Moreover, additional candidates will be tested and genetic analysis will be extended to all affected children.

Changes over time in delivery room management of extremely low birth weight infants in Italy

AIM To identify changes in practice between two historical periods (2002 vs. 2011) in early delivery room (DR) management of ELBWI in Italian tertiary centres. METHODS A questionnaire was sent to the directors of all Italian level III centres between April and August 2012. The same questionnaire was used in a national survey conducted in 2002. Among the participating centres, those that filled the questionnaire in both study periods were selected for inclusion in this study. RESULTS There was an 88% (n=76/86) and 92% (n=98/107) response rate in the 2 surveys, respectively. The two groups overlapped for 64 centres. During the study period, the use of polyethylene bags/wraps increased from 4.7% to 59.4% of the centres. The units using 100% oxygen concentrations to initiate resuscitation of ELBWI decreased from 56.2% to 6.2%. The approach to respiratory management was changed for the majority of the examined issues: positive pressure ventilation (PPV) administered through a T-piece resuscitator (from 14.0% to 85.9%); use of PEEP during PPV (from 35.9% to 95.3%); use of CPAP (from 43.1% to 86.2%). From 2002 to 2011, the percentages of ELBWI intubated in DR decreased in favor of those managed with N-CPAP; ELBWI receiving chest compressions and medications at birth were clinically comparable. CONCLUSIONS During the two study periods, the approach to the ELBWI at birth significantly changed. More attention was devoted to temperature control, use of oxygen, and less-invasive respiratory support. Nevertheless, some relevant interventions were not uniformly followed by the surveyed centres.

Oxygen administration for the resuscitation of term and preterm infants

Oxygen has been widely used in neonatal resuscitation for about 300 years. In October 2010, the International Liaison Committee on Neonatal Resuscitation released new guidelines. Based on experimental studies and randomized clinical trials, the recommendations on evaluation and monitoring of oxygenation status and oxygen supplementation in the delivery room were revised in detail. They include: inaccuracy of oxygenation clinical assessment (colour), mandatory use of pulse oximeter, specific saturation targets and oxygen concentrations during positive pressure ventilation in preterm and term infants. In this review, we describe oxygen management in the delivery room in terms of clinical assessment, monitoring, treatment and the gap of knowledge.

Delivery room management of extremely low birthweight infants shows marked geographical variations in Italy

To evaluate any geographical variations in practice and adherence to international guidelines for early delivery room management of extremely low birthweight (ELBW) infants in the North, Centre and South of Italy.

Delivery room management of extremely low birth weight infants in Italy: comparison between academic and non-academic birth centres

Abstract Objective: International Guidelines provide a standardised approach to newborn resuscitation in the DR and, in their most recent versions, recommendations dedicated to management of ELBWI were progressively increased. It is expected that introduction in clinical practice and dissemination of the most recent evidence should be more consistent in academic than in non-academic hospitals. The aim of the study was to compare adherence to the International Guidelines and consistency of practice in delivery room management of extremely low birth weight infants between academic and non-academic institutions. Methods: A questionnaire was sent to the directors of all Italian level III centres between April and August 2012. Results: There was a 92% (n = 98/107) response rate. Apart from polyethylene wrapping to optimise thermal control, perinatal management approach was comparable between academic and non-academic centres. Conclusions: There were minor differences in management of extremely low birth weight infants between Italian academic and non-academic institutions, apart from thermal management. Although there was a good, overall adherence to the International Guidelines for Neonatal Resuscitation, temperature management was not in accordance with official recommendations and every effort has to be done to improve this aspect.