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Summary Objective Bronchiolitis is one of the primary causes of hospitalization in infancy. We evaluated the effect of breastfeeding on the occurrence of hospitalization for bronchiolitis in the first year of life. Methods In a prospective cohort study, 1,814 newborns of =33 weeks of gestational age (wGA) were enrolled in 30 Italian Neonatology Units and followed-up for 1 year to assess hospitalizations for bronchiolitis. Children were grouped as ‘never breastfed’ and ‘ever breastfed’; these latter were further divided into those ‘exclusively breastfed’ and ‘breastfed associated with milk formula’. The risk of hospitalization for bronchiolitis was evaluated with survival analysis, and hazard ratios (HR) with 95% confidence interval [95% CI] were calculated. Results Among enrolled newborns 22.9% were ‘never breastfed’; in the breastfed group, 65% were ‘exclusively breastfed’ and 35% were ‘breastfed with associated milk formula’. At 12 months of age, the risk of hospitalization for bronchiolitis was significantly higher in the ‘never breastfed’ group (HR: 1.57; 95% CI: 1.00–2.48). ‘Breastfed associated with formula milk’ and ‘exclusively breastfed’ groups were at similar risk of hospitalization for bronchiolitis. This observed protective effect of maternal milk was not explained by the higher prevalence of conditions able to increase the risk of bronchiolitis among ‘never breastfed newborns’. Conclusions Breastfeeding, even in association with formula milk, reduces the risk of hospitalization for bronchiolitis during the first year of life. Encouraging breastfeeding might be an effective/inexpensive measure of prevention of lower respiratory tract infections in infancy.

This article summarizes the Italian Pediatric Society guideline on the management of the signs and symptoms of fever in children, prepared as part of the National Guideline Program (NGLP).Relevant publications in English and Italian were identified through searches of MEDLINE and the Cochrane Database of Systematic Reviews from their inception through December 31, 2007. Based on the consensus of a multidisciplinary expert panel, the strength of the recommendations was categorized into 5 grades (A-E) according to NGLP methodology.In the health care setting, axillary measurement of body temperature using a digital thermometer is recommended in children aged4 weeks; for children agedor =4 weeks, axillary measurement using a digital thermometer or tympanic measurement using an infrared thermometer is recommended. When body temperature is measured at home by parents or care-givers, axillary measurement using a digital thermometer is recommended for all children. Children who are afebrile when seen by the clinician but are reported to have had fever by their caregivers should be considered febrile. In special circumstances, high fever may be a predictive factor for severe bacterial infection. Use of physical methods of reducing fever is discouraged, except in the case of hyperthermia. Use of antipyretics-paracetamol (acetaminophen) or ibuprofen-is recommended only when fever is associated with discomfort. Combined or alternating use of antipyretics is discouraged. The dose of antipyretic should be based on the child's weight rather than age. Whenever possible, oral administration of paracetamol is preferable to rectal administration. Use of ibuprofen is not recommended in febrile children with chickenpox or dehydration. Use of ibuprofen or paracetamol is not contraindicated in febrile children with asthma. There is insufficient evidence to form any recommendations concerning fever in children with other chronic conditions, but caution is advised in cases of severe hepatic/renal failure or severe malnutrition. Newborns with fever should always be hospitalized because of the elevated risk of severe disease; paracetamol may be used, with the dose adjusted to gestational age. Use of paracetamol or ibuprofen is not effective in preventing febrile convulsion or the adverse effects of vaccines.

OBJECTIVES: We compared the relative effect of hypertensive disorders of pregnancy and chorioamnionitis on adverse neonatal outcomes in very preterm neonates, and studied whether gestational age (GA) modulates these effects. METHODS: A cohort of neonates 23 to 30 weeks' GA, born in 2008 to 2011 in 82 hospitals adhering to the Italian Neonatal Network, was analyzed. Infants born from mothers who had hypertensive disorders (N = 2096) were compared with those born after chorioamnionitis (N = 1510). Statistical analysis employed logistic models, adjusting for GA, hospital, and potential confounders. RESULTS: Overall mortality was higher after hypertension than after chorioamnionitis (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.08–1.80), but this relationship changed across GA weeks; the OR for hypertension was highest at low GA, whereas from 28 weeks' GA onward, mortality was higher for chorioamnionitis. For other outcomes, the relative risks were constant across GA; infants born after hypertension had an increased risk for bronchopulmonary dysplasia (OR, 2.20; 95% CI, 1.68–2.88) and severe retinopathy of prematurity (OR, 1.48; 95% CI, 1.02–2.15), whereas there was a lower risk for early-onset sepsis (OR, 0.25; 95% CI, 0.19–0.34), severe intraventricular hemorrhage (OR, 0.65; 95% CI, 0.48–0.88), periventricular leukomalacia (OR, 0.70; 95% CI, 0.48–1.01), and surgical necrotizing enterocolitis or gastrointestinal perforation (OR, 0.47; 95% CI, 0.31–0.72). CONCLUSIONS: Mortality and other adverse outcomes in very preterm infants depend on antecedents of preterm birth. Hypertension and chorioamnionitis are associated with different patterns of outcomes; for mortality, the effect changes across GA weeks.

The aim of this study was to assess the diagnostic value of IgM Western blotting (WB), IgA enzyme immunoassay (EIA), and DNA amplification by real-time PCR on Guthrie cards to retrospectively establish the diagnosis of congenital toxoplasmosis (CT). To this purpose, Guthrie cards were collected from 18 infants born to mothers with primary Toxoplasma gondii infection during pregnancy. Moreover, the analytical sensitivity of T. gondii PCR was assessed by testing mock dried blood specimens set up with several known DNA dilutions. IgM WB was demonstrated to be the most sensitive method. When the results of T. gondii DNA detection and specific IgM recovery were combined, retrospective CT diagnosis by using Guthrie cards was established in 3 out of 6 infected infants (sensitivity, 50%; 95% confidence interval, 26.8% to 73.2%). No positive PCR or serologic results were found in the group of 12 uninfected infants, demonstrating the excellent specificity of the three methods (95% confidence interval, 78.1% to 99.5%). The findings of the present study suggest that, in cases of missed diagnosis of CT at birth, analysis of Guthrie cards for children with compatible clinical findings after the perinatal period, in particular the combination of recovery of specific IgM antibodies and T. gondii DNA amplification, could be helpful. Nevertheless, since suboptimal conditions of storage of dried blood specimens can seriously affect sensitivity, negative results cannot rule out CT diagnosis. In contrast, because of the excellent specificity shown by IgM serologic testing and T. gondii DNA amplification on Guthrie cards, positive results obtained by either of the two methods should be considered diagnostic.

Background/Aims: As evidence accumulates relating to mother-to-child (vertical) transmission of hepatitis C virus (HCV), it is timely to draw up guidelines for the clinical management of HCV infected pregnant women and their children. Methods: A review of evidence from the European Paediatric HCV Network (EPHN) prospective study of HCV infected women and their children and other published studies. Meeting of EPHN clinical experts to reach a consensus on recommendations for management. Each recommendation was graded according to the level of evidence. Results/conclusions: Although several risk factors for mother-to-child transmission have been identified, none are modifiable and there are currently no interventions available to prevent vertical transmission of HCV. Data on timing of loss of maternal antibodies and reliability of diagnostic tests inform the optimum follow-up schedule for confirmation or exclusion of infection in children born to HCV infected women. Based on the current evidence, routine antenatal screening for HCV should not be introduced and neither elective caesarean section nor avoidance of breastfeeding should be recommended to HCV infected women to prevent mother-to-child transmission of HCV. HCV/HIV co-infected women should follow existing HIV guidelines. © 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

BACKGROUND: The effectiveness of Toxoplasma gondii (Tg) screening during pregnancy in areas with a low prevalence of the infection is debated. We investigate the Tg serological status, the rate of primary infection in a cohort of pregnant women and the rate of congenital toxoplasmosis among their infants during a 3-year period in an urban area with low Tg prevalence. METHODS: Demographic and Tg serological data for all pregnant women delivering from January 2009 to December 2011 were collected. All pregnant women with primary Tg infection during pregnancy and their infants were included in the study. RESULTS: In early pregnancy, 10,347 women underwent prenatal screening and 2308 (22.3%) had anti-Tg. The seroprevalence among non-native women was significantly higher than that among native women [32.8% vs. 19.1%, relative risk: 1.71, P < 0.001]. The incidence rate of primary Tg infection during pregnancy was 0.77%. Immigrant women were more likely to be infected during pregnancy than Italian women (relative risk: 4.88, P < 0.001). Tg infection was more frequent in women coming from Africa, Asia, Eastern Europe and South America. The CT incidence rate was 0.06%. All congenitally infected infants were born to immigrant mothers. CONCLUSIONS: Tg infection during pregnancy and congenital disease are more frequent in non-native mothers and their infants. Measures to prevent Tg exposition must be carefully explained to pregnant women, with a focus on specific habits in non-native women. Prenatal screening is still effective to select women for prenatal therapy aiming to decrease vertical transmission and to identify foetuses/newborns with congenital disease that could benefit from pre/postnatal antiparasitic therapy.

Mother-to-child transmission of hepatitis C virus (HCV) has been reported in up to 10% of cases and is much more likely to occur when the mother is also infected by HIV. Although women with HCV viremia are especially likely to transmit infection, the precise time when transmission takes place is not known. Transmission of HCV was examined in a prospective cohort study using data from the European Pediatric Hepatitis C Network. Fifty-four HCV-infected children were tested by the HCV RNA polymerase chain reaction technique within 3 days of birth. Nearly one third (31%) of newborn infants tested in the first 3 days of life had positive results. Transmission was more likely if the mother was coinfected by HIV, but the difference was not statistically significant. Mode of delivery, gender, and gestational age failed to predict the polymerase chain reaction (PCR) findings. Mean birth weight was significantly lower in infected children, but there was no significant difference when low-birth-weight infants were compared with normal-weight neonates. Breast-fed infants were marginally less likely than formula-fed infants to be PCR-positive. Four of 10 infants born to mothers who tested positive 4 weeks before delivery were themselves PCR-positive, but this was not the case for any of 4 infants born to PCR-negative women. A positive association between PCR positivity in the first 3 days of life and infection by genotype 1 remained significant after adjusting for several possible confounding factors. In 36 infants who were PCR-negative when born, the mean age at the first positive test was 3.9 months. Late intrauterine or intrapartum transmission was considered to be most likely for 27 infants who were PCR-negative at birth but -positive by age 3 months. Peripartum transmission seemed likely for 9 infants who were PCR-negative at birth and PCR-positive for the first time after 3 months. It appears that at least one third of HCV-infected infants, and possibly as many as half of them, acquire infection before birth. Should effective treatment be developed that is safer for pregnant women than are interferon-a and ribavirin, treatment optimally would begin early in pregnancy.

BACKGROUND: To evaluate whether physical and/or chemical features of gastro-esophageal reflux (GER) influence its relationship with apnea of prematurity (AOP). METHODS: Fifty-eight preterm newborns (GA ≤ 33 weeks) with recurrent apneas were studied by simultaneous polysomnography and combined impedance and pH monitoring, to analyze whether the correlation between GER and AOP varies according to the acidity, duration and height of GERs. KEY RESULTS: The frequency of apnea (number apnea/min) occurring after-GER [median (range) 0.07 (0-0.25)] was higher than the one detected in GER-free period [0.06 (0.04-0.13), P = 0.015], and also than the one detected before-GER [0 (0-0.8), P = 0.000]. The frequency of apneas detected in the 30'' after pH-GER [median (range), 0 min(-1) (0-1.09)] was higher than the frequency detected in the 30'' before [0 (0-0.91), P = 0.04]; even more, the frequency of apneas detected after non-acid MII-GER episodes [0 (0-2)] was significantly higher than the one detected before [0 (0-1), P = 0.000], whereas the frequency of apneas detected before acid MII-GER episodes [0 (0-0.67)] did not differ from the one detected after [0 (0-2), P = 0.137]. The frequency of pathological apneas detected in the 30'' after-GER (0 min(-1), range 0-0.55) was higher than the frequency detected before (0, range 0-0.09; P = 0.001). No difference in mean height or in mean duration was found between GERs correlated and those non-correlated to apnea. CONCLUSIONS & INFERENCES: Non-acid GER is responsible for a variable amount of AOP detected after-GER: this novel finding must be taken into consideration when a therapeutic strategy for this common problem is planned.

Surfactant given during brief intubation followed by immediate extubation on nasal continuous positive airway pressure [Intubation-Surfactant-Extubation (InSurE) approach] is used to treat respiratory distress syndrome in newborns. Our aim was to evaluate whether bilevel positive airway pressure (BiPAP) after InSurE failure is able to prevent the need for mechanical ventilation (MV). Chart data of infants with a birth weight1500 gr or GA32weeks undergoing InSurE in the period 2002-2008 in an Italian Tertiary Neonatal Intensive Care Unit were reviewed retrospectively. InSurE failure was defined as follows: FiO(2)0.4, respiratory acidosis or intractable apnoea within 1 week. After InSurE failure, newborns born before the implementation of BiPAP (historical control group) received MV, whereas those born after BiPAP implementation (BiPAP group) received BiPAP and underwent MV only if failure criteria persisted. The two groups were compared to evaluate whether BiPAP reduced the need for MV in the 7 days after InSurE failure.Six of twenty-two (27%) and 14 of the 38 (37%) infants failed InSurE in the two groups, respectively (p 0.05). Need for MV was 27% in the historical control group versus 0% in the BiPAP group (risk estimate, 3.38; 95% CI, 2.24, 5.09; p = 0.001). BiPAP reduced the need for MV after InSurE failure.

OBJECTIVE: Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by ∼50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab. METHODS: This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged ≤6 months at enrollment or children aged ≤24 months with chronic lung disease of prematurity who received 15 mg/kg palivizumab or motavizumab monthly. Secondary end points included outpatient medically attended lower respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and motavizumab serum concentrations. RESULTS: Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with palivizumab recipients, achieving noninferiority. Motavizumab was superior to palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events. CONCLUSIONS: Children receiving prophylaxis with motavizumab or palivizumab had low rates of RSV hospitalization; motavizumab recipients experienced 50% fewer RSV MALRIs than palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk.

Difficulties in mathematics have been described in very preterm children, but their origins are not well understood and may differ from other populations with specific learning disability. Very preterm children, children with learning disability, and typically developing children were compared in mathematics skills, using standardized tools, experimental tasks, and eye-tracker measures. We assessed symbolic and nonsymbolic magnitude comparisons, number knowledge, calculation, as well as cognitive skills of 103 Italian-speaking fourth and fifth graders. Compared to typically developing peers, very preterm children showed delays in number knowledge, slower reaction times in nonsymbolic magnitude comparisons, and an atypical gaze exploration characterized by more and shorter fixations that lacked a target preference. The profile of mathematics skills of very preterm children appeared different from that of children with learning disability. Although both populations showed mainly preserved cognitive skills and slower reaction times in nonsymbolic magnitude comparisons, children with specific learning disability showed more severe impairments in calculation and were slower in symbolic magnitude comparisons, compared to very preterm children. Including eye-tracking measures in preterm follow-up programs and planning tailored interventions are recommended.

BACKGROUND Preterm infants often require red blood cell (RBC) transfusions, which may impair splanchnic hemodynamics, thus predisposing to necrotizing enterocolitis (NEC). The aim of this study was to evaluate whether RBC transfusions alter splanchnic oxygenation patterns in response to enteral feeding in this population. MATERIALS AND METHODS Preterm neonates (gestational age

Preterm infants are at risk of developing gastrointestinal complications such as feeding intolerance and necrotizing enterocolitis. Near-infrared spectroscopy (NIRS) provides continuous monitoring of abdominal oxygenation (ArSO2) and could help to predict gastrointestinal complications in preterm neonates. In this prospective observational study, ArSO2 patterns at first enteral feed were evaluated by NIRS in 61 clinically stable preterm infants. Splanchnic-cerebral oxygenation ratio, which is a marker of gut hypoxia, was also calculated. ArSO2 and splanchnic-cerebral oxygenation ratio were significantly lower both at baseline and after feeding administration in infants who later developed feeding intolerance (n = 23). NIRS could help the early prediction of gastrointestinal complications in high-risk preterm infants.

The management of enteral feeds in preterm infants with a hemodynamically significant patent ductus arteriosus (hs-PDA) is a major challenge for neonatologists due to the fear of gastrointestinal (GI) complications. This review aims to analyze the available evidence on the complex relation between the presence and management of PDA, enteral feeding practices, and GI outcomes in the preterm population. There is limited evidence, based on small and heterogeneous trials, that hs-PDA may affect the splanchnic hemodynamic response to enteral feeds. While the presence of PDA seems a risk factor for adverse GI outcomes, the benefits of feeding withholding during pharmacological PDA treatment are controversial. The lack of robust evidence in support of or against a timely feeding introduction or feeding withholding during pharmacological PDA closure in preterm neonates does not allow to draw any related recommendation. While waiting for further data, the feeding management of this population should be carefully evaluated and possibly individualized on the basis of the infants’ hemodynamic and clinical characteristics. Large, multicentric trials would help to better clarify the physiological mechanisms underlying the development of gut hypoperfusion, and to evaluate the impact of enteral feeds on splanchnic hemodynamics in relation to PDA features and treatment.

This crossover study showed that non-nutritive sucking, provided with a pacifier in 30 preterm infants, had no effect on acid and nonacid gastro-esophageal reflux evaluated by esophageal pH-impedance, and thus may be reasonably used in preterm neonates with symptoms of gastro-esophageal reflux. Trial registration ClinicalTrials.gov : NCT02023216 .

Background Arachidonic acid (AA) and docosahexaenoic acid (DHA) are crucial for neural and visual development after premature birth. Preterm infants usually require tube feeding (TF) until the achievement of adequate oral feeding skills; the impact of TF on DHA and AA delivery has not been investigated yet. This study aimed to evaluate the effect of different TF techniques on the delivery of AA and DHA contained in human milk (HM). Methods HM samples (65 mL each) were collected and divided into three 20-mL aliquots. The remaining 5 mL served as baseline. Three TF techniques were simulated (1 for each aliquot): gravity bolus feeding (BF), 3-hour continuous feeding using a horizontal feeding pump, and 3-hour continuous feeding with the feeding pump angled at 45°. For horizontal continuous feeding (HCF) and 45° angled continuous feeding (ACF), aliquots delivered between 0 and 90 minutes (T1) and 91 and 180 minutes (T2) were collected separately. AA and DHA concentration was analyzed by gas chromatography/mass spectrometry and compared among the TF methods. DHA and AA delivery at T1 and T2 was also evaluated. Results Fifty-one simulated feeds were performed. DHA and AA amounts after BF and ACF did not differ significantly compared with baseline, whereas HCF resulted in significantly lower DHA and AA concentration. During T2, ACF delivered almost twice the DHA and AA amounts compared with T1. Conclusion The delivery of HM AA and DHA is significantly affected by TF, with potential clinical implications. When BF is not tolerated, ACF might represent a feasible alternative to reduce TF-related DHA and AA loss.

No abstract available

Background: Guidelines currently do not recommend the routine use of chest x-ray (CXR) in bronchiolitis. However, CXR is still performed in a high percentage of cases, mainly to diagnose or rule out pneumonia. The inappropriate use of CXR results in children exposure to ionizing radiations and increased medical costs. Lung Ultrasound (LUS) has become an emerging diagnostic tool for diagnosing pneumonia in the last decades. The purpose of this study was to assess the diagnostic accuracy and reliability of LUS for the detection of pneumonia in hospitalized children with bronchiolitis and to evaluate the agreement between LUS and CXR in diagnosing pneumonia in these patients. Methods: We enrolled children admitted to our hospital in 2016-2017 with a diagnosis of bronchiolitis and undergone CXR because of clinical suspicion of concomitant pneumonia. LUS was performed in each child by a pediatrician blinded to the patient's clinical, laboratory and CXR findings. An exploratory analysis was done in the first 30 patients to evaluate the inter-observer agreement between a pediatrician and a radiologist who independently performed LUS. The diagnosis of pneumonia was established by an expert clinician based on the recommendations of the British Thoracic Society guidelines. Results: Eighty seven children with bronchiolitis were investigated. A final diagnosis of concomitant pneumonia was made in 25 patients. Sensitivity and specificity of LUS for the diagnosis of pneumonia were 100% and 83.9% respectively, with an area under-the-curve of 0.92, while CXR showed a sensitivity of 96% and specificity of 87.1%. When only consolidation > 1 cm was considered consistent with pneumonia, the specificity of LUS increased to 98.4% and the sensitivity decreased to 80.0%, with an area under-the-curve of 0.89. Cohen's kappa between pediatrician and radiologist sonologists in the first 30 patients showed an almost perfect agreement in diagnosing pneumonia by LUS (K 0.93). Conclusions: This study shows the good accuracy of LUS in diagnosing pneumonia in children with clinical bronchiolitis. When including only consolidation size > 1 cm, specificity of LUS was higher than CXR, avoiding the need to perform CXR in these patients. Added benefit of LUS included high inter-observer agreement. Trial registration: Identifier: NCT03280732. Registered 12 September 2017 (retrospectively registered).

Only a small fraction of drugs widely used in neonatal intensive care units (NICU) are specifically authorized for this population. Even if unlicensed or off-label use is necessary, it is associated with increased adverse drug reactions, which must be carefully weighed against expected benefits. In particular, renal damage is frequent among preterm babies, and is considered a predisposing factor for the development of chronic kidney disease in adulthood. Apart from specific conditions affecting premature neonates (e.g. respiratory distress syndrome, perinatal asphyxia), drugs play an important role in impairing renal function because of well-known nephrotoxicity and/or interaction with renal developmental factors. From a review of the available studies on drug use in NICU patients, we identified and described the most commonly administered drugs that are correlated to renal damage. Early detection of kidney injury is becoming an essential aspects for clinicians because of the limited number of biomarkers applicable in the neonatal population. Postnatal changes of biochemical processes that influence pharmacokinetic and pharmacodynamic aspects need to be further investigated in order to better understand the mechanisms of drug toxicity in this population. The most promising strategies for dose adjustment and therapeutic schemes are discussed. The purpose of this review was to describe current knowledge on drug use among premature babies and their implication in kidney injury development, as well as to highlight available strategies for early detection of renal damage. ispartof: Drug Safety vol:38 issue:6 pages:535-551 ispartof: location:New Zealand status: published

Preterm infants with antenatal absent or reversed end diastolic flow (AREDF) in umbilical arteries are at major risk for gastrointestinal (GI) complications, such as necrotizing enterocolitis, intestinal perforation and feeding intolerance. Near-infrared spectroscopy (NIRS) provides continuous monitoring of splanchnic oxygenation (SrSO2) and might represent a useful tool to predict GI outcomes in this high-risk population.This observational, pilot study assessed feed-related SrSO2 patterns at enteral feeding introduction and full enteral feeding (FEF) achievement in twenty AREDF infants with gestational age ≤34 weeks. Enrolled infants were divided into two groups according to the development vs. lack of GI complications.Infants developing GI complications showed significantly lower SrSO2 and increased splanchnic oxygen extraction in response to enteral feeds at both enteral feeding introduction and FEF.The potential role of these findings in predicting GI complications in AREDF preterm infants seems promising and deserves further evaluation.

This review will examine the role of oxidative stress (OS) in the pathogenesis of necrotizing enterocolitis (NEC) and explore potential preventive and therapeutic antioxidant strategies. Preterm infants are particularly exposed to OS as a result of several perinatal stimuli and constitutive defective antioxidant defenses. For this reason, OS damage represents a contributing factor to several complications of prematurity, including necrotizing enterocolitis (NEC). Being NEC a multifactorial disease, OS may act as downstream component of the pathogenetic cascade. To counteract OS in preterm infants with NEC, several antioxidant strategies have been proposed and different antioxidant compounds have been experimented. It is well known that human milk (HM) is an important source of antioxidants. At the same time, the role of an exclusive HM diet is well recognized in the prevention of NEC. However, donor HM (DHM) processing may impair antioxidant properties. As DHM is becoming a common nutritional intervention for high risk PI, the antioxidant status of preterm and DHM and potential ways to preserve its antioxidant capacity may merit further investigation.

Background: An increasing body of research on typically and atypically developing infants has shown that motor skills play an important role in language development. To date, however, the role of specific object exploration skills for early gesture and vocabulary development has not been investigated in extremely low gestational age infants (ELGA, GA < 28 weeks), who are at greater risk for motor and language delays than full-term (FT) infants. Purpose: This longitudinal study examined relations between 6-month active exploratory behaviors and 12- month word comprehension, gestures and vocal production, controlling for cognitive performance and neonatal condition (ELGA vs FT). Methods: Forty infants, 20 ELGA and 20 FT, and their mothers participated in the study. Mother-infant play interaction was video-recorded at 6 and 12 months. Oral and manual object exploration at 6 months and spontaneous gestures and vocal production at 12 months were coded. Word comprehension was evaluated with the Italian version of the MacArthur-Bates CDI parent questionnaire at 12 months. Cognitive performance was examined with the Griffiths Mental Developmental Scales at 6 months and the Bayley-III Scales at 12 months. Results: Regression analyses showed that after accounting for cognitive performance and neonatal condition, oral exploration was related to word comprehension, and manual exploration to gestures and vocal production in the overall sample. Conclusions: Cascading effects of specific object exploration skills on gestures and language comprehension and production in preterm infants and FT infants are discussed. Clinical implications for early assessment of and interventions involving object exploration skills, which may affect language development, are considered for the preterm population.

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Background Care coordination is widely recognized as a key element of care for patients with chronic and complex medical conditions and their families. In care for children with special health care needs the Family Pediatrician (FP) plays a central role as care coordinator. This study aims to evaluate the FPs’ activities of care coordination for children with special health care needs in the pediatric primary care setting, using an on-line measurement tool. Methods Within the prospective cohort study SpeNK (Special Needs Kids), newborns and children with special health care needs were recruited at discharge from three hospital facilities in Bologna province, from October 1st 2012 to September 30th 2014. Their FPs were invited to complete a questionnaire (SpeNK-FP) at each encounter for the patient during a 9-month period after hospital discharge. SpeNK-FP was developed by adapting the Care Coordination Measurement Tool (CCMT©) developed by Antonelli et al., to the Italian organizational context. The outcome of interest, derived from the questionnaire, is inappropriate use of services. Results Forty FPs completed assessments for 49 children at each of 382 clinical encounters. The majority of children (71.4%) had special health care needs, without complicating social issues. FPs reported “no need for care coordination” in 50.8% of the encounters and 41.1% of records about patient needs requiring care coordination. The most common activity implemented to meet children’s needs was telephone contact with a medical provider. According to FPs, 80% of encounters prevented inappropriate services use. In multivariate regression, pediatric-specialist contact (telephone or in person) was associated with reduced odds of physician report of preventable hospitalization (OR = 0.06, 95% CI 0.01–0.42, p = 0.005). Conclusions The study shows the potential for FPs in Italy to serve as care coordinators and facilitate the implementation of integrated care pathways for children with special health care needs. Electronic supplementary material The online version of this article (doi:10.1186/s13052-017-0342-3) contains supplementary material, which is available to authorized users.

Background There are no Italian data regarding the strategies for preventing neonatal group B streptococcal (GBS) infection. We conducted a national survey in order to explore obstetrical, neonatal and microbiological practices for the GBS prevention. Methods Three distinct questionnaires were sent to obstetricians, neonatologists and microbiologists. Questionnaires included data on prenatal GBS screening, maternal risk factors, intrapartum antibiotic prophylaxis, microbiological information concerning specimen processing and GBS antimicrobial susceptibility. Results All respondent obstetrical units used the culture-based screening approach to identify women who should receive intrapartum antibiotic prophylaxis, and more than half of the microbiological laboratories (58%) reported using specimen processing consistent with CDC guidelines. Most neonatal units (89 out of 107, 82%) reported using protocols for preventing GBS early-onset sepsis consistent with CDC guidelines. Conclusions The screening-based strategy is largely prevalent in Italy, and most protocols for preventing GBS early-onset sepsis are consistent with CDC guidelines. However, we found discrepancies in practices among centers that may reflect the lack of Italian guidelines issued by public health organizations.

Skin disinfection with chlorhexidine gluconate has not been standardized in preterm infants. We present 5 cases of chemical burns that occurred within the first 2 days of life in very low birth weight neonates after skin disinfection with aqueous and alcohol-based chlorhexidine solutions.

Serology has a pivotal role in the diagnosis of congenital syphilis (CS), but problems arise because of the passive transfer of IgG antibodies across the placenta. The aim of this study was to assess the diagnostic value of a comparative Western blot (WB) method finalized to match the IgG immunological profiles of mothers and their own babies at birth in order to differentiate between passively transmitted maternal antibodies and antibodies synthesized by the infants against Treponema pallidum . Thirty infants born to mothers with unknown or inadequate treatment for syphilis were entered in a retrospective study, conducted at St. Orsola-Malpighi Hospital, Bologna, Italy. All of the infants underwent clinical, instrumental, and laboratory examinations, including IgM WB testing. For the retrospective study, an IgG WB assay was performed by blotting T. pallidum antigens onto nitrocellulose sheets and incubating the strips with serum specimens from mother-child pairs. CS was diagnosed in 11 out of the 30 enrolled infants; 9/11 cases received the definitive diagnosis within the first week of life, whereas the remaining two were diagnosed later because of increasing serological test titers. The use of the comparative IgG WB testing performed with serum samples from mother-child pairs allowed a correct CS diagnosis in 10/11 cases. The CS diagnosis was improved by a strategy combining comparative IgG WB results with IgM WB results, leading to a sensitivity of 100%. The comparative IgG WB test is thus a welcome addition to the conventional laboratory methods used for CS diagnosis, allowing identification and adequate treatment of infected infants and avoiding unnecessary therapy of uninfected newborns.

Necrotizing enterocolitis (NEC) is the most severe gastrointestinal complication of prematurity. Surgery, either peritoneal drainage placement or laparotomy with resection of the intestinal necrotic tracts, is the definitive treatment of perforated NEC; however, when clinical conditions contraindicate surgical approaches, little is known about medical treatments adjuvant or alternative to surgery. Octreotide is a synthetic somatostatin analog that inhibits pancreatic secretion and leads to splanchnic vasoconstriction. In preterm neonates, it is mainly used off-label for chylothorax and congenital hyperinsulinism, whereas gastrointestinal indications are limited. We describe the case of a critically ill extremely low birth weight infant with perforated NEC, who had unsuccessfully undergone peritoneal drainage placement and laparotomy. Her unstable condition contraindicated a further laparotomy, thus off-label treatment with octreotide was attempted. No adverse events occurred. The infant’s condition gradually improved and progressive reduction of peritoneal outputs and successful resolution of pneumoperitoneum were achieved, with no relapse after octreotide discontinuation.

Different factors are known to influence the early gut colonization in newborns, among them the perinatal use of antibiotics. On the other hand, the effect on the baby of the administration of antibiotics to the mother during labor, referred to as intrapartum antibiotic prophylaxis (IAP), has received less attention, although routinely used in group B Streptococcus positive women to prevent the infection in newborns. In this work, the fecal microbiota of neonates born to mothers receiving IAP and of control subjects were compared taking advantage for the first time of high-throughput DNA sequencing technology. Seven different 16S rDNA hypervariable regions (V2, V3, V4, V6 + V7, V8, and V9) were amplified and sequenced using the Ion Torrent Personal Genome Machine. The results obtained showed significant differences in the microbial composition of newborns born to mothers who had received IAP, with a lower abundance of Actinobacteria and Bacteroidetes as well as an overrepresentation of Proteobacteria. Considering that the seven hypervariable regions showed different discriminant ability in the taxonomic identification, further analyses were performed on the V4 region evidencing in IAP infants a reduced microbial richness and biodiversity, as well as a lower number of bacterial families with a predominance of Enterobacteriaceae members. In addition, this analysis pointed out a significant reduction in Bifidobacterium spp. strains. The reduced abundance of these beneficial microorganisms, together with the increased amount of potentially pathogenic bacteria, may suggest that IAP infants are more exposed to gastrointestinal or generally health disorders later in age.

Background. The neonatal immune system is not fully developed at birth; newborns have adequate lymphocytes counts but these cells lack function.Objective. To assess the activity of T-cells and the influence of the main perinatal factors in very preterm infants (birth weight < 1500 g).Design. Blood samples from 59 preterm infants (21/59 were dizygotic twins) were collected at birth and at 30 days of life to measure CD4+ T-cell activity using the ImmuKnow™ assay. Fifteen healthy adults were included as a control group.Results. CD4+ T-cell activity was lower in VLBW infants compared with adults (p<0.001). Twins showed lower immune activity compared to singletons (p=0.005). Infants born vaginally showed higher CD4+ T-cell activity compared to those born by C-section (p=0.031); infants born after prolonged Premature Rupture of Membranes (pPROM) showed higher CD4+ T-cell activity at birth (p=0.002) compared to infants born without pPROM. Low CD4+ T-cell activity at birth is associated with necrotizing enterocolitis (NEC) in the first week of life (p=0.049).Conclusions. Preterm infants show a lack in CD4+ T-cell activity at birth. Perinatal factors such as intrauterine inflammation, mode of delivery, and zygosity can influence the adaptive immune activation capacity at birth and can contribute to exposing these infants to serious complications such as NEC.

Prophylaxis with zidovudine and 3 doses of nevirapine (NVP) is recommended for infants born to HIV-1 infected untreated mothers to prevent HIV-1 mother-to-child transmission. However little is known about NVP pharmacokinetics in neonates, mostly in preterm infants. We performed therapeutic monitoring of NVP plasma concentrations in a 32-week preterm HIV-1 exposed infant born to an infected untreated mother. With the recommended regimen, an intense NVP exposure was observed, with NVP plasma levels exceeding the target concentration by up to 40 times, suggesting that when a laboratory assessment of NVP plasma concentrations is available, it may be useful to monitor and optimize drug exposure. Prophylaxis with zidovudine and 3 doses of nevirapine (NVP) is recommended for infants born to HIV-1 infected untreated mothers to prevent HIV-1 mother-to-child transmission. However little is known about NVP pharmacokinetics in neonates, mostly in preterm infants. We performed therapeutic monitoring of NVP plasma concentrations in a 32-week preterm HIV-1 exposed infant born to an infected untreated mother. With the recommended regimen, an intense NVP exposure was observed, with NVP plasma levels exceeding the target concentration by up to 40 times, suggesting that when a laboratory assessment of NVP plasma concentrations is available, it may be useful to monitor and optimize drug exposure.

Extremely low gestational age (ELGA, GA.

Primary immunodeficiencies are rare inherited disorders that may lead to frequent and often severe acute respiratory infections. Respiratory syncytial virus (RSV) is one of the most frequent pathogens during early infancy and the infection is more severe in immunocompromised infants than in healthy infants, as a result of impaired T- and B-cell immune response unable to efficaciously neutralize viral replication, with subsequent increased viral shedding and potentially lethal lower respiratory tract infection. Several authors have reported a severe clinical course after RSV infections in infants and children with primary and acquired immunodeficiencies. Environmental prophylaxis is essential in order to reduce the infection during the epidemic season in hospitalized immunocompromised infants. Prophylaxis with palivizumab, a humanized monoclonal antibody against the RSV F protein, is currently recommended in high-risk infants born prematurely, with chronic lung disease or congenital heart disease. Currently however the prophylaxis is not routinely recommended in infants with primary immunodeficiency, although some authors propose the extension of prophylaxis to this high risk population.

Human parechovirus (HpeV) is an important emerging infection in young infants, able to cause sepsis-like disease and meningoencephalitis, especially in newborns. Among the 19 identified genotypes, HPeV1, 3 and 6 are the most common types involved in human infections; HPeV3 is the type mainly responsible for neonatal infections and for infections involving the central nervous system. Signs and symptoms overlap with those of a bacterial infection and patients are usually treated with broad spectrum antibiotics. In the majority of cases lumbar puncture shows absence of pleocytosis, even in the presence of signs of meningitis. In these cases, cerebrospinal fluid cultures are negative for bacteria but, in the absence of diagnosis of viral infection, a full and unnecessary antibiotic cycle is often continued. Moreover, high sensitivity neuroimaging, i.e., magnetic resonance, and follow-up are often missed, thus resulting in substandard care. Availability of a real time PCR assay for HPeV RNA allows rapid and sensitive diagnosis as long as the disease is suspected. In this case study, we present cases of HPeV infections in newborns requiring neonatal intensive care admission, discuss their optimal management, and highlight the most relevant findings in the literature.