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Abstract: Objectives: To assess the clinical safety of DTaP–IPV–HIb–HBV hexavalent immunization in very premature infants and to verify if the first administration of vaccine is by itself a reason for close monitoring hospitalized VLBW infants born at less than 31 weeks’ gestation. Patients and methods: Eighty-one preterm newborns less than 31 weeks’ gestational age, admitted in the NICU, were eligible to be immunized with hexavalent vaccine under close monitoring, including pre-and post-immunization continuous monitoring of heart rate, oxygen saturation, respiratory rate, resistance index at the anterior cerebral artery and ECG cQT interval. Results: Of the 81 eligible premature newborns, 36 were graduated from the NICU before the least date for immunization, at 7 weeks of age. The other 45 were vaccinated in the NICU and entered the study. Twenty-three of them were under medical treatment for chronic disease at the time of the immunization while 22 were healthy and stable. Five infants (11%) had apnoea/bradycardia/desaturation, related to vaccine administration and required medical support. All five infants were in the group of newborns with chronic disease (21.7% prevalence of adverse reactions in this group). No significant variation of cQT or RI before and after the immunization was observed either in the whole groups of patients or in the five infants who showed cardio-respiratory events related to vaccination. Conclusions: Hexavalent DTaP–IPV–HIb–HBV immunization is not associated with cardiac electric activity and cerebral blood flow variations in both stable and unstable very premature infants. However, it can cause apnoea/bradycardia/desaturation in premature babies with chronic disease. Therefore, if the baby is in the NICU for chronic diseases at 2 months post-birth, it should be monitored for apnoea, bradycardia and desaturation in association with vaccination. Hospitalized healthy preterm infants without chronic disease and therapy seem to be less vulnerable to cardio-respiratory adverse reactions. Nevertheless, it is advisable to immunize and monitor them at 8 weeks before discharge instead of possibly delaying immunization for several weeks and not monitor them. [Copyright &y& Elsevier]

Healthy 4-6 y old children from Italy and Sweden immunized with DTPa and inactivated or oral polio vaccines at 3, 5 and 11-12 months of age, received 1 dose of combined DTPa-IPV ( n= 211) or DTPa+IPV as separate doses ( n= 205) in a randomized trial. The pre-booster seroprotection rates were similar in each group and were above 60% against all antigens except diphtheria (31.3% and 37.0%) and PT (21.5% and 25.9%) in the DTPa-IPV and DTPa+IPV groups, respectively. At least 99.5% of subjects had seroprotective antibody levels against diphtheria, tetanus and polioviruses and ≥96% showed a vaccine response to each pertussis antigen after vaccination. Post-booster antibody levels increased at least 51-fold for anti-diphtheria and anti-tetanus, at least 18-fold for anti-pertussis antibodies and at least 32-fold for antibodies against all 3 poliovirus types, compared to prior levels. DTPa-IPV was comparable to DTPa+IPV in terms of seroprotection rates and mean antibody levels against each vaccine antigen. Similar reactogenicity profiles were observed between groups including swelling >50 mm [13% (9.1, 18.7) vs 17% (12.4, 23.4)] or involving an adjacent joint [0% (-,-) vs 1.5% (0.3, 4.3)] and were consistent with previous reports. The combined DTPa-IPV vaccine could be used to add DTP valences to the IPV vaccine currently given to children in Scandinavia and Italy at 4-6 y of age and reinforce protection against 4 diseases. [ABSTRACT FROM AUTHOR]

Immunoglobulin G (IgG) antibody titres against pertussis antigens, Bordetella pertussis-specific proliferation and cytokine production by peripheral blood mononuclear cells (PBMCs) were evaluated at the age of 5–6 years in 13 children who had been pre-term infants with a gestational age (GA) of ≤31 weeks, 10 who had been pre-term infants with a GA of 32–37 weeks, and 15 who had been term infants with a GA of 38–42 weeks. All of the infants had been immunised with a combined diphtheria, tetanus, tricomponent acellular pertussis and hepatitis B vaccine (DTaP–HBV) at 3, 5, and 11 months of post-natal age. Our results show that the long-term immune responses induced by primary pertussis vaccination in the pre-term infants (especially those with a GA of ≤31 weeks) were qualitatively and quantitatively lower than those observed in the term infants. In order to maintain an adequate pertussis-specific immune response, in term children a booster at 5–6 years of age may be suggested, whereas in pre-term an earlier booster should be useful. [Copyright &y& Elsevier]

Presents commentaries and replies to articles that appeared in the periodical `Pediatrics' that deal with pediatrics. Discussion on the prevention of perinatal transmission of chronic hepatitis B surface antigen carrier state; Comments on the diagnosis of hemorrhagic periventricular leukomalacia using ultrasonography; Relationship of the Kawasaki disease with an abnormal responseto Epstein-Barr virus; Reaction of the United States Food and Drug Administration on the issue of dead space in tracheal tubes.

Abstract: The hypothesis that nutrition during critical windows in fetal and early life can program long-term health is intriguing and has a potentially strong implication for public health and pediatric nutritional practice. Specifically, it has been hypothesized that there are critical periods in the differentiation and maturation of the central nervous system during which environmental and nutritional factors can produce long-term structural and/or functional changes. Many studies have focused on the relationship between nutrition during early life and long-term neurodevelopmental outcome, leading to contrasting results: in fact, although experimental data in animals and short-term follow-up studies indicate a possible relationship between nutrition during early life and neurodevelopment, the results of long-term follow-up studies are more controversial and less convincing. [Copyright &y& Elsevier]

Respiratory syncytial virus is a worldwide pathogen agent responsible for frequent respiratory tract infections that may become severe and potentially lethal in high risk infants and adults. Several studies have been performed to investigate the immune response that determines the clinical course of the infection. In the present paper, we review the literature on viral, environmental, and host factors influencing virus response; the mechanisms of the immune response; and the action of nonimmunological factors. These mechanisms have often been studied in animal models and in the present review we also summarize the main findings obtained from animal models as well as the limits of each of these models. Understanding the lung response involved in the pathogenesis of these respiratory infections could be useful in improving the preventive strategies against respiratory syncytial virus. [ABSTRACT FROM AUTHOR]

Aim: To estimate the association between the inpatient admissions and Emergency Department (ED) visits before age of 18 years and adulthood‐onset first‐episode psychosis (FEP). Methods: We conducted a FEP incidence and case–control study and calculated the odds ratios (ORs) for incident FEP associated with inpatient admissions and ED visits prior to age of 18 years, adjusting our results for cannabis use, parental socio‐economic class and childhood trauma. Results: In multivariate logistic regression analysis, odds of FEP increased significantly if the participant had a history of at least one inpatient admission (OR = 3.52; 95% confidence interval [95%CI] 1.07‐11.54; P =.04) or at least one ED visit (OR = 8.93; 95%CI 2.41‐33.14; P =.001) before age of 18. The associations remained significant adjusting for cannabis use, education, parental socio‐economic class and childhood trauma. Conclusion: Consistently with the socio‐neurodevelopmental model, we found a significant association between a positive history of hospital care in childhood and adulthood‐onset psychosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Key points: Non‐invasive simultaneous multiparametric monitoring allows the in vivo evaluation of cerebral and cardiovascular haemodynamic responses to different types of recurrent episodes of intermittent hypoxia and/or bradycardia, also defined as cardio‐respiratory events (CRE), in preterm neonates during postnatal transition.By decreasing left cardiac output, bradycardia further contributes to cerebral hypoxia during CRE.The presence of a haemodynamically significant patent ductus arteriosus results in a deeper impairment of cerebral oxygen status in response to CRE, whereas the brain‐sparing remodelling of the fetal circulation resulting from placental insufficiency is associated with more favourable haemodynamic responses to intermittent hypoxia.During transition, the haemodynamic impact of CRE is influenced not only by the event type, but also by specific clinical features; this highlights the importance of developing individualized approaches to reduce the hypoxic burden in this delicate phase. The present observational prospective study aimed to investigate cerebral and cardiovascular haemodynamic responses to different types of cardio‐respiratory events (CRE) in preterm infants during postnatal transition, as well as evaluate the impact of relevant clinical characteristics. Infants with gestational age (GA) <32 weeks and/or birth weight <1500 g were enrolled after birth. Cerebral oxygenation index (cTOI), fractional oxygen extraction (cFTOE), cardiac output (CO), cardiac contractility (iCON) and systemic vascular resistances (sVR) were simultaneously monitored over the first 72 h by near‐infrared spectroscopy and electrical velocimetry. CRE were clustered into isolated bradycardia (IB), isolated desaturation (ID) and combined desaturation/bradycardia (DB). For each parameter, percentage changes from baseline (%Δ) were calculated. The impact of different CRE types and clinical variables on %Δ was evaluated with generalized estimating equations. In total, 1426 events were analysed. %ΔcTOI significantly differed among ID, IB and DB (P < 0.001), with the latter showing the greatest drop. %ΔcFTOE decreased significantly during DB (P < 0.001) and ID (P < 0.001) compared to IB. DB and IB were associated with more negative %ΔCO (P < 0.001) and more positive %ΔsVR (P < 0.001) compared to ID. A slight iCON reduction was observed during DB compared to ID (P = 0.043). Antenatal umbilical Doppler impairment, GA and the presence of a haemodynamically significant patent ductus arteriosus had a significant independent impact on %ΔcTOI, %ΔcFTOE and %ΔCO. During the transitional period, the haemodynamic responses to CRE are influenced by the event type and by specific neonatal characteristics, suggesting the importance of targeted individualized approaches for minimizing the risk of cerebral injury in the preterm population. Key points: Non‐invasive simultaneous multiparametric monitoring allows the in vivo evaluation of cerebral and cardiovascular haemodynamic responses to different types of recurrent episodes of intermittent hypoxia and/or bradycardia, also defined as cardio‐respiratory events (CRE), in preterm neonates during postnatal transition.By decreasing left cardiac output, bradycardia further contributes to cerebral hypoxia during CRE.The presence of a haemodynamically significant patent ductus arteriosus results in a deeper impairment of cerebral oxygen status in response to CRE, whereas the brain‐sparing remodelling of the fetal circulation resulting from placental insufficiency is associated with more favourable haemodynamic responses to intermittent hypoxia.During transition, the haemodynamic impact of CRE is influenced not only by the event type, but also by specific clinical features; this highlights the importance of developing individualized approaches to reduce the hypoxic burden in this delicate phase. [ABSTRACT FROM AUTHOR]

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 < 32 weeks and/or birth weight < 1500 g) requiring RBC transfusions for anemia underwent a 12-hour Near Infrared Spectroscopy monitoring of splanchnic (SrSO2 ) and cerebral (CrSO2 ) oxygenation, including the transfusion period, one feed before and one after. Splanchnic-cerebral oxygenation ratio (SCOR) was also calculated. Patterns of CrSO2 , SrSO2 , and SCOR changes from baseline (Δ) in response to feed before and after transfusion were analyzed.Results: Twenty neonates were enrolled; none of them developed any gastrointestinal complication within 48 hours after transfusion. Pre-transfusion ΔSrSO2 and ΔSCOR increased significantly in response to feeding; on the contrary, a significant post-prandial decrease of ΔSrSO2 and ΔSCOR occurred after transfusion (p < 0.05). No difference in pre- and post-transfusion ΔCrSO2 patterns was observed.Conclusions: In preterm infants, RBC transfusions may alter splanchnic oxygenation response to enteral feeds. Whether these changes are involved in the pathogenesis of transfusion-associated NEC has to be evaluated in further larger trials. [ABSTRACT FROM AUTHOR]

Background: Very preterm (VPT) children showed delays in reading, spelling and maths, but their academic achievement profile is not clearly understood.Aims: VPT children were compared with children with specific learning disorders (SLD) and typically developing (TD) children on academic achievement, considering cognitive and linguistic phenotypic markers. A learning profile analysis was also performed.Methods: We included 170 10-year old monolingual Italian-speaking children (37 VPT, 28 SLD, 105 TD) assessing cognitive, linguistic and academic skills.Results: On academic achievements VPT children fell behind TD peers in some reading (text speed, comprehension), spelling (non-word), and math (number knowledge, written calculations and problem-solving) tasks. SLD children underperformed in all academic tasks with respect to VPT and TD peers. Concerning cognitive and linguistic phenotypic markers, compared to TD peers, VPT children showed lower scores in verbal IQ and phonological fluency, SLD children in phonological processing and rapid automatized naming. VPT children showed a higher rate of at-risk performance in reading compared to TD group, but a minor percentage of impaired profiles and comorbidity among learning areas compared to SLD group.Conclusions and Implications: The academic achievement profile of VPT children shows persistent delays, but it differs to that of SLD children, since delays are less widespread and severe, and differences were found in phenotypic markers and comorbidity. Follow-up programs and effective interventions are needed for VPT children. [ABSTRACT FROM AUTHOR]

Highlights • Six-month oral exploration is related to12-month word comprehension. • Six-month manual exploration is related to 12-month gesture and vocal production. • Early oral and manual exploration assessment is relevant for language development. • Active object exploration should be promoted in extremely preterm infants. Abstract 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. [ABSTRACT FROM AUTHOR]

Background: Strategies for prevention of HIV-1 mother-to-child transmission (PMTCT) have been continuously optimized. However, cases of vertical transmission continue to occur in high-income countries. Objectives: To investigate changes in PMTCT strategies adopted by Italian clinicians over time and to evaluate risk factors for transmission. Methods: Data from mother-child pairs prospectively collected by the Italian Register, born in Italy in 1996-2016, were analyzed. Risk factors for MTCT were explored by logistic regression analyses. Results: Six thousand five hundred three children (348 infections) were included. In our cohort, the proportion of children born to foreign mothers increased from 18.3% (563/3078) in 1996%-2003% to 66.2% (559/857) in 2011-2016 (P < 0.0001). Combination neonatal prophylaxis use significantly (P < 0.0001) increased over time, reaching 6.3% (56/857) after 2010, and it was largely (4.2%) adopted in early preterm infants. The proportion of vaginal deliveries in women with undetectable viral load (VL) increased over time and was 9.9% (85/857) in 2011-2016; no infection occurred among them. In children followed up since birth MTCT, rate was 3.5% (96/ 2783) in 1996-2003; 1.4% (36/2480) in 2004-2010; and 1.1% (9/ 835) in 2011-2016. At a multivariate analysis, factors associated with MTCT were vaginal delivery with detectable or missing VL or nonelective caesarean delivery, prematurity, breastfeeding, lack of maternal or neonatal antiretroviral therapy, detectable maternal VL, and age at first observation. Previously described increased risk of offspring of immigrant women was not confirmed. Conclusions: Risk of MTCT in Italy is ongoing, even in recent years, underling the need for implementation of the current screening program in pregnancy. Large combination neonatal prophylaxis use in preterm infants was observed, even if data on safety and efficacy in prematures are poor. [ABSTRACT FROM AUTHOR]

Background Congenital cytomegalovirus (cCMV) infection is responsible of a high burden of neurosensory impairment in children. Objectives To report incidence and consequences of ophthalmological abnormalities in infants with cCMV infection and better define their long-term ophthalmological management. Study design Infants with cCMV infection were enrolled in a 6-year follow-up. Infants were classified as symptomatic or asymptomatic based on complete clinical, laboratory and instrumental evaluations. All infants underwent funduscopic evaluation in neonatal period, and yearly complete ophthalmological evaluation, including funduscopic, motility and visual acuity assessments. Results Forty-eight infants were enrolled, 18/48 (37.5%) symptomatic and 30/48 (62.5%) asymptomatic. Mean duration of follow-up was 34.9 ± 22.2 vs. 34.8 ± 20.1 months (P = 0.98). Funduscopic abnormalities were identified in neonatal period in 7/18 (39%) symptomatic infants and in none of the infants without other clinical and instrumental abnormalities at birth (P < 0.001); chorioretinal scars were the most common finding (5/18 cases, 28%). Strabismus was detected in 1/18 (5.5%) symptomatic infants during the first years of life. Visual impairment at last follow-up evaluation was suspected or detected in 4/18 (22%) symptomatic infants and in none of the asymptomatic infants at birth (P = 0.01). Ophthalmological abnormalities were associated with other signs of central nervous system (CNS) involvement (P<0.001). No correlation was found with the type of maternal infection. Conclusions Ophthalmological abnormalities were common in symptomatic infants though often not associated with long-term visual impairment, and correlated with the presence of CNS involvement. Neonatal and periodical ophthalmological evaluations throughout childhood seem prudential for symptomatic babies. No ophthalmological abnormalities were detected in asymptomatic infants, who might therefore undergo more deferred evaluations. [ABSTRACT FROM AUTHOR]

Although early object exploration is considered a key ability for subsequent achievements, very few studies have analyzed its development in extremely low gestational age infants (ELGA- GA <28 weeks), whose early motor skills are delayed. Moreover, no studies have examined its developmental relationship with cognitive and language skills. The present study examined developmental change in Motor Object Exploration (MOE) and different types of MOE (Holding, Oral, Manual and Manual Rhythmic Exploration) in 20 ELGA and 20 full term (FT) infants observed during mother-infant play interaction at 6 and 9 months. It also explored whether specific types of MOE were longitudinally related to 24-month language and cognitive abilities (GMDS-R scores). ELGA infants increased MOE duration from 6 to 9 months, eliminating the initial difference with FT infants. In addition, ELGA infants showed a different pattern of Oral Exploration, that did not increase at 6 months and decrease at 9 months. Oral and Manual Exploration durations at 6 months were longitudinally related to 24-month GMDS-R language and cognitive performance scores respectively. We discuss the relevance of assessing early exploratory abilities in ELGA infants in order to implement customized intervention programs for supporting the development of these skills. [ABSTRACT FROM AUTHOR]

The neurodevelopmental impact of fentanyl given to preterm newborns for pain control is still unknown. The aim of this study was to assess the neurodevelopmental impact of 2 regimens of fentanyl administration by a prospective follow-up evaluation. In our previous multicenter, double-blind, randomized controlled trial, 131 mechanically ventilated newborns (gestational age ≤32 weeks) were randomized to fentanyl (continuous infusion of fentanyl + open label boluses of fentanyl) or placebo (continuous infusion of placebo + open label boluses of fentanyl). Infant development was evaluated using Griffiths Mental Developmental Scales (Griffiths, 1996) until 24 months of corrected age by trained psychologists who were not aware of the group allocation. 106/131 infants survived at discharge; 3 died after discharge, 25 were lost to follow-up (12 in the fentanyl and 13 in the placebo group). Seventy-eight patients were evaluated at 2 years of corrected age. Children in the fentanyl group, compared with those in the placebo group, obtained significantly lower Griffiths general developmental quotient (mean [SD]: 89.95 [13.64] vs 97.18 [12.72], P = 0.024) together with the scores on the eye-hand coordination (mean [SD]: 89.09 [12.13] vs 99.19 [13.19], P = 0.002) and performance skills (mean [SD]: 79.71 [15.80] vs 90.09 [15.28], P = 0.009) scales. After adjustment for clinical confounders (gestational age, CRIB score, and sex) only eye-hand co-ordination was associated with fentanyl infusion. This study demonstrates that continuous infusion of fentanyl in very preterm infants, given at 1 mcg·kg·h during mechanical ventilation, is associated with a significant decrease in eye and hand co-ordination skills. Longer follow-up is needed to evaluate the impact on future motor, cognitive, and behavioral functions. [ABSTRACT FROM AUTHOR]

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, = 0.005). p 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: This cross-sectional study focused on the effect of very preterm (VPT) birth on language development by analysing phonological, lexical, grammatical, and pragmatic skills and assessing the role of cognitive and memory skills.Method: Sixty children (29 males, 31 females) born VPT (<32wks) aged 5 years were compared with 60 children with typical development. The linguistic assessment was performed by administering a battery of Italian tests for the evaluation of language; cognitive and memory skills were assessed by Raven's coloured progressive matrices and digit span subtest (Wechsler Intelligence Scale for Children [WISC-III]).Results: Children born VPT showed delays in lexical (comprehension: z-score difference -1.18; 95% confidence interval [CI] -1.60 to -0.77; naming: -0.88; 95% CI -1.19 to -0.58) and pragmatic skills (comprehension: -0.76; 95% CI -1.02 to -0.49; narrative production: -0.47; 95% CI -0.72 to -0.23). Delays in phonology and grammar were less diffuse, involving productive skills (-1.09; 95% CI -1.64 to -0.54; -0.48; 95% CI -0.85 to -0.12, respectively), and were dependent by cognitive and memory skills. Lexical delays were more specific.Interpretation: The linguistic profile of children born preterm is characterized by some abilities more impaired than others. This highlights the need of a linguistic assessment at the end of preschool age in order to plan a focused intervention aimed at improving lexical and pragmatic skills. [ABSTRACT FROM AUTHOR]

Delays in the motor domain have been frequently observed in preterm children, especially those born at an extremely low gestational age (ELGA;<28 weeks GA). However, early motor exploration has received relatively little attention despite its relevance for object knowledge and its impact on cognitive and language development. The present study aimed at comparing early object exploration in 20 ELGA and 20 full-term (FT) infants at 6 months of age during a 5-minute mother-infant play interaction. Object engagement (visual vs manual), visual object engagement (no act vs reach), manual object engagement (passive vs active), and active object manipulation (mouthing, transferring, banging, turn/rotating, shaking, fingering) were analyzed. Moreover, the Griffiths Mental Development Scales 0-2 years (1996) were administered to the infants. Relative to FT peers, ELGA infants spent more time in visual engagement, and less time in manual engagement, active manipulation, mouthing, and turning/rotating. Moreover, they had lower scores on general psychomotor development, eye & hand coordination, and performance abilities. Close relationships emerged between manual object engagement and psychomotor development. Clinical implications of these results in terms of early evaluation of action schemes in ELGA infants and the provision of intervention programs for supporting these abilities are discussed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The faecal microbiota composition of infants born to mothers receiving intrapartum antibiotic prophylaxis with ampicillin against group B Streptococcus was compared with that of control infants, at day 7 and 30 of life. Recruited newborns were both exclusive breastfed and mixed fed, in order to also study the effect of dietary factors on the microbiota composition. Massive parallel sequencing of the V3-V4 region of the 16S rRNA gene and qPCR analysis were performed. Antibiotic prophylaxis caused the most marked changes on the microbiota in breastfed infants, mainly resulting in a higher relative abundance of Enterobacteriaceae, compared with control infants (52% vs. 14%, p = 0.044) and mixed-fed infants (52% vs. 16%, p = 0.13 NS) at day 7 and in a lower bacterial diversity compared to mixed-fed infants and controls. Bifidobacteria were also particularly vulnerable and abundances were reduced in breastfed (p = 0.001) and mixed-fed antibiotic treated groups compared to non-treated groups. Reductions in bifidobacteria in antibiotic treated infants were also confirmed by qPCR. By day 30, the bifidobacterial population recovered and abundances significantly increased in both breastfed (p = 0.025) and mixed-fed (p = 0.013) antibiotic treated groups, whereas Enterobacteriaceae abundances remained highest in the breastfed antibiotic treated group (44%), compared with control infants (16%) and mixed-fed antibiotic treated group (28%). This study has therefore demonstrated the short term consequences of maternal intrapartum antibiotic prophylaxis on the infant faecal microbial population, particularly in that of breastfed infants. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Despite the predictive value of early spontaneous communication for identifying risk for later language concerns, very little research has focused on these behaviors in extremely low-gestational-age infants (ELGA<28 weeks) or on their relationship with motor development. In this study, communicative behaviors (gestures, vocal utterances and their coordination) were evaluated during mother-infant play interactions in 20 ELGA infants and 20 full-term infants (FT) at 12 months (corrected age for ELGA infants). Relationships between gestures and motor skills, evaluated using the Bayley-III Scales were also examined. ELGA infants, compared with FT infants, showed less advanced communicative, motor, and cognitive skills. Giving and representational gestures were produced at a lower rate by ELGA infants. In addition, pointing gestures and words were produced by a lower percentage of ELGA infants. Significant positive correlations between gestures (pointing and representational gestures) and fine motor skills were found in the ELGA group. We discuss the relevance of examining spontaneous communicative behaviors and motor skills as potential indices of early development that may be useful for clinical assessment and intervention with ELGA infants. [ABSTRACT FROM AUTHOR]

Extremely low gestational age (ELGA, GA < 28 weeks) preterm children are at high risk for linguistic impairments; however, their lexical comprehension and production as well as lexical categories in their early language acquisition have not been specifically examined via direct tools. Our study examines lexical comprehension and production as well as gestural production in ELGA children by focusing on noun and predicate acquisition. Forty monolingual ELGA children (mean GA of 26.7 weeks) and 40 full-term (FT) children were assessed at two years of corrected chronological age (CCA) using a test of noun and predicate comprehension and production (PiNG) and the Italian MB-CDI. Noun comprehension and production were delayed in ELGA compared with FT children, as documented by the low number of correct responses and the large number of errors, i.e., incorrect responses and no-response items, and by the types of incorrect responses, i.e., fewer semantically related responses, in noun production. Regarding predicate comprehension and production, a higher frequency of no responses was reported by ELGA children and these children also presented a lower frequency of bimodal spoken-gestural responses in predicate production than FT children. A delayed vocabulary size as demonstrated by the MB-CDI, was exhibited by one-fourth of the ELGA children, who were also unable to complete the predicate subtest. These findings highlight that noun comprehension and production are delayed in ELGA children at two years of CCA and are the most important indexes for the direct evaluation of their lexical abilities and delay. The types of incorrect responses and bimodal spoken-gestural responses were proven to be useful indexes for evaluating the noun and predicate level of acquisition and to plan early focused interventions. Learning outcomes: After reading this manuscript, the reader will understand (a) the differences in noun and predicate comprehension and production between ELGA and FT children and the indexes of lexical delays exhibited by ELGA children at 2;0 (CCA); (b) the relevance of evaluating errors (incorrect response and no response), the types of incorrect responses (semantically related and unrelated) and the modality of the responses (unimodal spoken and bimodal spoken-gestural) in noun and predicate production to understand the difficulties experienced by ELGA children in representing and expressing meanings; and (c) the need to plan specific interventions to support spoken and gestural modalities in lexical comprehension and production in ELGA children by focusing on noun and predicate acquisition. [ABSTRACT FROM AUTHOR]

Introduction: Children with special health care needs are an exponentially growing population needing integrated health care programmes that involve primary, community, hospital and tertiary care services. The aims of the study are (1) to develop and validate the Special Needs Kids Questionnaire (SpeNK-Q) designed to measure parents' perspective on continuity of care for children with special health care needs and (2) to evaluate the continuity of care based on parental experiences in this population. Methods: SpeNK-Q was derived from a previous qualitative study and was based on Haggerty's constructs of informational, management and relational continuity. Parents of preterm birth children completed the 20-item SpeNK-Q at the second or subsequent planned follow-up visit after the child's hospital discharge. Principal component analysis was used to examine the structure of the instrument. Results: Principal component analysis of 101 questionnaires administered allowed us to identify five factors explaining 60.2% of item variance: informational continuity; coordination of care; continuity of family--paediatrician relationship; family support; information on care plan. Conclusions and discussion: SpeNK-Q proved to be a psychometrically promising instrument. Its utilisation could improve the identification of areas for service development, the delivery of coordinated care and support policy makers in redesigning integrated services. [ABSTRACT FROM AUTHOR]

Extremely low gestational age children (ELGA, born below 28 weeks of GA) represent the most at-risk preterm group in terms of survival, developmental sequelae and rates of impairment and cognitive delays. However, the impact of an extremely preterm birth on mother-infant co-regulation and affective intensity which may affect early infant's development has not been investigated. Based on a relational dynamic system approach, our study aimed to investigate the quality of co-regulation and affective intensity during spontaneous play interaction in 20 mother-infant ELGA dyads compared to 20 full-term (FT) dyads at 12 months (corrected age for ELGA infants). Relationships between the quality of dyadic co-regulation and the infant's level of cognitive, motor and language development were also investigated. The quality of dyadic co-regulation was assessed using the Revised Relational Coding System (R-RCS) by Fogel et al. (2003), the mothers' and infants' affective intensity was coded using a coding system by Lunkenheimer, Olson, Hollenstein, Sameroff, and Winter (2011). Infants' development was assessed using the Bayley Scales (BSID-III, 2006). With respect to FT dyads, ELGA dyads were characterised by less frequent symmetric and more frequent unilateral co-regulation patterns and by less positive and more neutral affective intensity of both infants and mothers. Cognitive, motor and language scores were lower in ELGA infants than in FT infants. Symmetrical co-regulation was related to motor scores in ELGA infants, and to cognitive scores in FT infants. Our findings contribute to the literature by demonstrating the difficulties of ELGA mother-infant dyads at 12 months in sharing the symmetric co-regulation and positive affective intensity and how symmetric co-regulation is strictly related to motor development in ELGA infants. Based on these findings, intervention programmes to foster joint attention, active involvement and positive affective intensity in ELGA dyads and infants' development in the first year of life should be designed. [ABSTRACT FROM AUTHOR]

Extremely low gestational age children (ELGA, born below 28 weeks of GA) represent the most at-risk preterm group in terms of survival, developmental sequelae and rates of impairment and cognitive delays. However, the impact of an extremely preterm birth on mother–infant co-regulation and affective intensity which may affect early infant's development has not been investigated. Based on a relational dynamic system approach, our study aimed to investigate the quality of co-regulation and affective intensity during spontaneous play interaction in 20 mother–infant ELGA dyads compared to 20 full-term (FT) dyads at 12 months (corrected age for ELGA infants). Relationships between the quality of dyadic co-regulation and the infant's level of cognitive, motor and language development were also investigated. The quality of dyadic co-regulation was assessed using the Revised Relational Coding System (R-RCS) by Fogel et al. (2003) , the mothers’ and infants’ affective intensity was coded using a coding system by Lunkenheimer, Olson, Hollenstein, Sameroff, and Winter (2011) . Infants’ development was assessed using the Bayley Scales (BSID-III, 2006). With respect to FT dyads, ELGA dyads were characterised by less frequent symmetric and more frequent unilateral co-regulation patterns and by less positive and more neutral affective intensity of both infants and mothers. Cognitive, motor and language scores were lower in ELGA infants than in FT infants. Symmetrical co-regulation was related to motor scores in ELGA infants, and to cognitive scores in FT infants. Our findings contribute to the literature by demonstrating the difficulties of ELGA mother–infant dyads at 12 months in sharing the symmetric co-regulation and positive affective intensity and how symmetric co-regulation is strictly related to motor development in ELGA infants. Based on these findings, intervention programmes to foster joint attention, active involvement and positive affective intensity in ELGA dyads and infants’ development in the first year of life should be designed. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is an established nosocomial pathogen with frequent multidrug resistance. The immaturity of the immune system along with intravascular lines and empirical antibiotic treatments place hospitalized preterm infants at major risk of MRSA infection. We report a case of MRSA mandibular osteomyelitis complicating a persistent S. aureus bacteremia in a 23-week preterm infant. From the first weeks of life, the infant showed recurrent C-reactive protein (CRP) elevation, associated with S. aureus bacteremia. Antibiotic courses, including vancomycin and linezolid, were performed with transitory normalization of blood parameters. On day 74, the infant suddenly deteriorated and showed a significant increase of both CRP and procalcitonin. Empiric vancomycin and piperacillin-tazobactam treatment was started; nevertheless, she developed a progressive hard swelling of neck and mandible. Radiological evaluation revealed a mandibular osteomyelitis complicated by an abscess, whose culture grew MRSA. Vancomycin was thus changed to teicoplanin and complete clinical and radiological healing was gradually achieved. In the presence of major risk factors, persistent bacteremia and nonspecific symptoms, a localized focus of infection should be suspected. Microbiological diagnosis should always be attempted and antibiotic treatment should be guided by both susceptibility results and clinical response. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To explore parents' experiences and perceptions on informational, management and relational continuity of care for children with special health care needs from hospitalization to the first months after discharge to the home. Methods: Semi-structured interviews and a focus group were carried out to capture parents' experiences and perceptions. Transcripts were analyzed using a directed approach to the qualitative content analysis. Results: 16 families participated to this study: 13 were involved in interviews (10 face-to-face and 3 by phone) and 3 in a focus group, within 1-6 months after discharge from the University Hospital of Bologna (S.Orsola/Malpighi) and from hospitals of Bologna Province. To parents of children with special health care needs, the three domains of continuity of care were relevant in a whole but with different key elements during hospitalization, at discharge and after discharge. Moreover, empowerment emerged from parents' narratives as essential to help parents cope with the transition from the hospital setting to the new responsibilities connected with the home care of their child. Parent's perceptions about the family pediatrician concerned his/her centrality in the activation and coordination of the healthcare network. Moreover, parents exhibited different attitudes towards involvement in decision making: some wished and expected to be involved, others preferred not to be involved. Conclusions: Care coordination for children with special care needs is a complex process that need to be attended to during the hospitalization phase and after discharge to the community. The findings of this study may contribute to elucidating the perceptions and experiences of parents with children with special health care needs about the continuity of care from hospital to community care. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the effect of human milk feeding during NICU hospitalization on neurodevelopment at 24 months of corrected age in very low birth weight infants. A cohort of 316 very low birth weight newborns (weight ≤ 1500 g) was prospectively enrolled in a follow-up program on admission to the Neonatal Intensive Care Unit of S. Orsola Hospital, Bologna, Italy, from January 2005 to June 2011. Neurodevelopment was evaluated at 24 months corrected age using the Griffiths Mental Development Scale. The effect of human milk nutrition on neurodevelopment was first investigated using a multiple linear regression model, to adjust for the effects of gestational age, small for gestational age, complications at birth and during hospitalization, growth restriction at discharge and socio-economic status. Path analysis was then used to refine the multiple regression model, taking into account the relationships among predictors and their temporal sequence. Human milk feeding during NICU hospitalization and higher socio-economic status were associated with better neurodevelopment at 24 months in both models. In the path analysis model intraventricular hemorrhage—periventricular leukomalacia and growth restriction at discharge proved to be directly and independently associated with poorer neurodevelopment. Gestational age and growth restriction at birth had indirect significant effects on neurodevelopment, which were mediated by complications that occurred at birth and during hospitalization, growth restriction at discharge and type of feeding. In conclusion, our findings suggest that mother’s human milk feeding during hospitalization can be encouraged because it may improve neurodevelopment at 24 months corrected age. [ABSTRACT FROM AUTHOR]

Several factors are known to influence the early colonization of the gut in newborns. Among them, the use of antibiotics on the mother during labor, referred to as intrapartum antibiotic prophylaxis (IAP), has scarcely been investigated, although this practice is routinely used in group B Streptococcus (GBS)-positive women. This work is therefore aimed at verifying whether IAP can influence the main microbial groups of the newborn gut microbiota at an early stage of microbial establishment. Fifty-two newborns were recruited: 26 born by mothers negative to GBS (control group) and 26 by mothers positive to GBS and subjected to IAP with ampicillin (IAP group). Selected microbial groups ( Lactobacillus spp., Bidobacterium spp., Bacteroides fragilis, Clostridium difficile, and Escherichia coli) were quantified with real-time PCR on DNA extracted from newborn feces. Further analysis was performed within the Bidobacterium genus by using DGGE after amplification with genus-specific primers. Results obtained showed a significant decrease of the bifidobacteria counts after antibiotic treatment of the mother. Bifidobacteria were found to be affected by IAP not only quantitatively but also qualitatively. In fact, IAP determined a decrement in the frequency of Bidobacterium breve, Bidobacterium bifidum, and Bidobacterium dentium with respect to the control group. Moreover, this study has preliminarily evaluated that some bifidobacterial strains, previously selected for use in infants, have antibacterial properties against GBS and are therefore potential candidates for being applied as probiotics for the prevention of GBS infections. [ABSTRACT FROM AUTHOR]

Background Current literature provides limited data on the hemodynamic changes that may occur during bi-level continuous positive airway pressure (CPAP) support in preterm infants. However, the application of a positive end-expiratory pressure may be transmitted to the heart and the great vessels resulting in changes of central blood flow. Objective To assess changes in central blood flow in infants with respiratory distress syndrome (RDS) during bi-level CPAP support. Design A prospective study was performed in a cohort of 18 Very-Low-Birth-Weight Infants who were put on nasal CPAP support (4-5 cmH2O) because they developed RDS within the first 24-72 hours of life. Each subject was switched to bi-level CPAP support (Phigh 8 cmH2O, Plow 4-5 cmH2O, Thigh 0.5-0.6 seconds, 20 breaths/min) for an hour. An echocardiographic study and a capillary gas analysis were performed before and after the change of respiratory support. Results No differences between n-CPAP and bi-level CPAP in left ventricular output (LVO, 222.17 ± 81.4 vs 211.4 ± 75.3 ml/kg/min), right ventricular output (RVO, 287.8 ± 96 vs 283.4 ± 87.4 ml/kg/min) and superior vena cava flow (SVC, 135.38 ± 47.8 vs 137.48 ± 46.6 ml/kg/min) were observed. The hemodynamic characteristics of the ductus arteriosus were similar. A significant decrease in pCO2 levels after bi-level CPAP ventilation was observed; pCO2 variations did not correlate with modifications of central blood flow (LVO: ρ = 0.11, p = 0,657; RVO: ρ = -0.307, p = 0.216; SVC: ρ = -0.13, p = 0.197). Conclusions Central blood flow doesn't change during bi-level CPAP support, which could become a hemodinamically safe tool for the treatment of RDS in preterm infants. [ABSTRACT FROM AUTHOR]

Background Current literature provides limited data on the hemodynamic changes that may occur during bi-level continuous positive airway pressure (CPAP) support in preterm infants. However, the application of a positive end-expiratory pressure may be transmitted to the heart and the great vessels resulting in changes of central blood flow. Objective To assess changes in central blood flow in infants with respiratory distress syndrome (RDS) during bi-level CPAP support. Design A prospective study was performed in a cohort of 18 Very-Low-Birth-Weight Infants who were put on nasal CPAP support (4-5 cmH2O) because they developed RDS within the first 24-72 hours of life. Each subject was switched to bi-level CPAP support (Phigh 8 cmH2O, Plow 4-5 cmH2O, Thigh 0.5-0.6 seconds, 20 breaths/min) for an hour. An echocardiographic study and a capillary gas analysis were performed before and after the change of respiratory support. Results No differences between n-CPAP and bi-level CPAP in left ventricular output (LVO, 222.17 ± 81.4 vs 211.4 ± 75.3 ml/kg/min), right ventricular output (RVO, 287.8 ± 96 vs 283.4 ± 87.4 ml/kg/min) and superior vena cava flow (SVC, 135.38 ± 47.8 vs 137.48 ± 46.6 ml/kg/min) were observed. The hemodynamic characteristics of the ductus arteriosus were similar. A significant decrease in pCO2 levels after bi-level CPAP ventilation was observed; pCO2 variations did not correlate with modifications of central blood flow (LVO: ρ = 0.11, p = 0,657; RVO: ρ = -0.307, p = 0.216; SVC: ρ = -0.13, p = 0.197). Conclusions Central blood flow doesn't change during bi-level CPAP support, which could become a hemodinamically safe tool for the treatment of RDS in preterm infants. [ABSTRACT FROM AUTHOR]

Highlights: [•] ELGA children show delays in language, motor and cognitive skills from 1st to 3rd year. [•] ELGA children's gap increases in motor skills, is stable in language and cognitive skills. [•] Great inter-individual rate of change in language is evident in ELGA and FT children. [•] Growth curve analyses allow identification of differences at individual and group level. [Copyright &y& Elsevier]

Abstract: Background: Serious difficulties in formal mathematical skills have been identified in preterm children. By contrast, basic-level numerical skills like magnitude judgments have not yet been tested in these children. Aims: The aim of the present research was to investigate whether preterm birth also affects these basic numerical abilities, with particular attention to the transition from preschool to formal education. Method: One hundred-forty very preterm children and 60 age-matched controls were recruited in a cross-sectional study at 6 and 8years of age. Magnitude comparison tasks with non-symbolic dot displays or symbolic Arabic-number stimuli, measuring accuracy and reaction time, were administered to participants. We also investigated explicit number knowledge, as well as general cognitive developmental levels, to gain a broader picture of preterm abilities. Results: Despite no general cognitive delay, the more simple approximate non-symbolic representation of numerical magnitude was affected by preterm birth, with slower reaction times at both ages compared to controls. Additionally, clear difficulties in the construction of the symbolic representation of numerical magnitude and in explicit number knowledge emerged in the 6-year-old preterm children, with a recovery from this serious delay finally by 8years. Conclusions: The serious delays identified here in basic numerical abilities in preterm children, despite normal IQ, point to the need for further studies in order to elucidate the relationship between basic numerical abilities and subsequent difficulties in formal mathematic achievement at school. [Copyright &y& Elsevier]

Abstract: Purpose: To assess the diagnostic and prognostic value of cerebral magnetic resonance imaging (cMRI) in comparison with that of cerebral ultrasound (cUS) in predicting neurodevelopmental outcome in newborns with congenital cytomegalovirus (CMV) infection. Methods: Forty CMV-congenitally infected newborns underwent cUS and cMRI within the first month of life. Clinical course, laboratory findings, visual/hearing function and neurodevelopmental outcome were documented. Results: Thirty newborns showed normal cMRI, cUS and hearing/visual function in the first month of life; none showed CMV-related abnormalities at follow-up. Six newborns showed pathological cMRI and cUS findings (pseudocystis, ventriculomegaly, calcifications, cerebellar hypoplasia) but cMRI provided additional information (white matter abnormalities in three cases, lissencephaly/polymicrogyria in one and a cyst of the temporal lobe in another one); cerebral calcifications were detected in 3/6 infants by cUS but only in 2/6 by cMRI. Four of these 6 infants showed severe neurodevelopmental impairment and five showed deafness during follow-up. Three newborns had a normal cUS, but cMRI documented white matter abnormalities and in one case also cerebellar hypoplasia; all showed neurodevelopmental impairment and two were deaf at follow-up. One more newborn showed normal cUS and cMRI, but brainstem auditory evoked responses were abnormal; psychomotor development was normal at follow-up. Conclusions: Compared with cUS, cMRI disclosed additional pathological findings in CMV-congenitally infected newborns. cUS is a readily available screening tool useful in the identification of infected newborns with major cerebral involvement. Further studies with a larger sample size are needed to determine the prognostic role of MRI, particularly regarding isolated white matter lesions. [Copyright &y& Elsevier]

Background: To elucidate the role of prenatal, neonatal and early postnatal variables in influencing the achievement of full enteral feeding (FEF) in very low birth weight (VLBW) infants and to determine whether neonatal intensive care units (NICUs) differ in this outcome. Methods: Population-based retrospective cohort study using data on 1,864 VLBW infants drawn from the “Emilia-Romagna Perinatal Network” Registry from 2004 to 2009. The outcome of interest was time to FEF achievement. Eleven prenatal, neonatal and early postnatal variables and the study NICUs were selected as potential predictors of time to FEF. Parametric survival analysis was used to model time to FEF as a function of the predictors. Marginal effects were used to obtain adjusted estimates of median time to FEF for specific subgroups of infants. Results: Lower gestational age, exclusive formula feeding, higher CRIB II score, maternal hypertension, cesarean delivery, SGA and PDA predicted delayed FEF. NICUs proved to be heterogeneous in terms of FEF achievement. Newborns with PDA had a 4.2 days longer predicted median time to FEF compared to those without PDA; newborns exclusively formula-fed had a 1.4 days longer time to FEF compared to those fed human milk. Conclusions: The results of our study suggest that time to FEF is influenced by clinical variables and NICU-specific practices. Knowledge of the variables associated with delayed/earlier FEF achievement could help in improving specific aspects of routine clinical management of VLBW infants and to reduce practice variability. [ABSTRACT FROM AUTHOR]

Background: Surfactant treatment reduces respiratory morbidity and mortality in preterm infants. Data on its haemodynamic consequences are conflicting. The aim was to characterise the haemodynamic effects of surfactant treatment on cardiac function in preterm newborns with respiratory distress syndrome (RDS). Methods: Preterm infants (gestational age <34 weeks, birth weight <2000 g) with RDS, who received surfactant within 72 hours of life, were recruited. Echocardiography was performed before surfactant, and 2 and 24 hours after. Left and right ventricular peak systolic, early diastolic and late diastolic myocardial velocities were measured using Tissue Doppler Imaging (TDI), while characteristics of the ductus arteriosus, pulmonary artery pressure, right ventricular (RVO) and left ventricular output were measured by standard echocardiography. Tricuspidal Annular Plane Systolic Excursion (TAPSE) was measured on the free wall of the tricuspid annulus. Results: Fourteen patients were studied. Surfactant was associated with a decrease in pulmonary pressure and an increase in RVO. The improvement of right ventricular function was also confirmed by a significant increase in right peak systolic velocity and in TAPSE. Left ventricular velocities did not change significantly after surfactant. Conclusions: Surfactant administration in preterm infants with RDS did not impair myocardial contractility and was followed by increased RVO, in agreement with other parameters of right ventricular function. TDI and TAPSE appeared to be reliable and feasible in this population. The addition of TDI and TAPSE to standard neonatal echocardiography may provide additional information about cardiac function. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Apnea of prematurity (AOP) occurs frequently in preterm infants and a variable proportion of AOP can be induced by gastroesophageal reflux (GER). Conservative treatment, including dietary modifications, should be the first-line approach for both GER and GER-related apneas in this population. Objectives: To evaluate the efficacy of a starch-thickened preterm formula (PF) in reducing the frequency of apneas related to GER. Methods: Preterm infants with AOP were studied by combined impedance and pH monitoring and polysomnography. The 6-hour study period included two feeds, one of a commercially available PF and one of the same formula thickened with amylopectin (TPF). GER indexes, apneas and GER-related apneas detected after TPF and PF feeds were compared by Wilcoxon signed-rank test. Results: 24 infants were studied. During 140 h of registration, 289 apneas (147 after TPF and 142 after PF; p = 0.876), and 861 GER episodes (400 after TPF and 461 after PF; p = 0.465) were recorded. No difference in the number of AOP was found between TPF and PF. A significant reduction in acid exposure was found after TPF; there was no influence on non-acid GER indexes. The frequency of GER-related apneas did not differ between TPF and PF. Conclusions: A formula thickened with amylopectin did not reduce the number of AOP or GER-related apneas. It reduced acid GER features but had no effect on non-acid GER indexes. Future research should focus on exploring different conservative strategies to treat GER-related apneas in preterm infants. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare the rate of neonatal respiratory morbidity in singletons versus twins delivered by pre-labour caesarean section. Study design: Uncomplicated pregnancies delivered by prelabor caesarean section at 34+0 to 37+6 weeks’ gestation were retrospectively selected. For both singletons and twins caesarean delivery was undertaken electively only after amniocentesis and if the lecithin/sphingomyelin ratio was ≥2. Neonatal respiratory morbidity was compared in twins versus singletons. Results: 241 singletons and 100 twin neonates were included. Overall neonatal respiratory morbidity was comparable between the two groups (25/241 (11.7%) versus 7/100 (7%), p =.331). Between 34+0 and 36+6 weeks, however, the risk was higher among singleton than twins (15/46 (32.6%) versus 6/72 (8.3%), p <.001). At multiple regression, dichorionicity, gestational age at delivery ≥37 weeks and female sex independently decreased the risk of neonatal respiratory morbidity. Conclusion: The risk of neonatal respiratory morbidity after elective caesarean section seems lower among twins, especially prior to 37+0 weeks. [Copyright &y& Elsevier]

Abstract: Background: Brain Cooling (BC) represents the elective treatment in asphyxiated newborns. Amplitude Integrated Electroencephalography (aEEG) and Near Infrared Spectroscopy (NIRS) monitoring may help to evaluate changes in cerebral electrical activity and cerebral hemodynamics during hypothermia. Objectives: To evaluate the prognostic value of aEEG time course and NIRS data in asphyxiated cooled infants. Methods: Twelve term neonates admitted to our NICU with moderate-severe Hypoxic-Ischemic Encephalopathy (HIE) underwent selective BC. aEEG and NIRS monitoring were started as soon as possible and maintained during the whole hypothermic treatment. Follow-up was scheduled at regular intervals; adverse outcome was defined as death, cerebral palsy (CP) or global quotient <88.7 at Griffiths’ Scale. Results: 2/12 Infants died, 2 developed CP, 1 was normal at 6months of age and then lost at follow-up and 7 showed a normal outcome at least at 1year of age. The aEEG background pattern at 24h of life was abnormal in 10 newborns; only 4 of them developed an adverse outcome, whereas the 2 infants with a normal aEEG developed normally. In infants with adverse outcome NIRS showed a higher Tissue Oxygenation Index (TOI) than those with normal outcome (80.0±10.5% vs 66.9±7.0%, p =0.057; 79.7±9.4% vs 67.1±7.9%, p =0.034; 80.2±8.8% vs 71.6±5.9%, p =0.069 at 6, 12 and 24h of life, respectively). Conclusions: The aEEG background pattern at 24h of life loses its positive predictive value after BC implementation; TOI could be useful to predict early on infants that may benefit from other innovative therapies. [Copyright &y& Elsevier]

Gastroesophageal reflux (GOR) is very common among preterm infants, due to several physiological mechanisms. Although GOR should not be usually considered a pathological condition, its therapeutic management still represents a controversial issue among neonatologists; pharmacological overtreatment, often unuseful and potentially harmful, is increasingly widespread. Hence, a stepwise approach, firstly promoting conservative strategies such as body positioning, milk thickening, or changes of feeding modalities, should be considered the most advisable choice in preterm infants with GOR. This review focuses on the conservative management of GOR in the preterm population, aiming to provide a complete overview, based on currently available evidence, on potential benefits and adverse effects of nonpharmacological measures. Nonpharmacological management of GOR might represent a useful tool for neonatologists to reduce the use of antireflux medications, which should be limited to selected cases of symptomatic babies. [ABSTRACT FROM AUTHOR]

Although gastroesophageal reflux (GER) is a very common phenomenon among preterm infants, its therapeutic management is still an issue of debate among neonatologists. A step-wise approach should be advisable, firstly promoting nonpharmacological interventions and limiting drugs to selected infants unresponsive to the conservative measures or who are suffering from severe GER with clinical complications. Despite of this, a concerning pharmacological overtreatment has been increasingly reported. Most of the antireflux drugs, however, have not been specifically assessed in preterm infants; moreover, serious adverse effects have been noticed in association to their administration. This review mainly aims to draw the state of the art regarding the pharmacological management of GER in preterm infants, analyzing the best piecies of evidence currently available on the most prescribed antireflux drugs. Although further trials are required, sodium alginate-based formulations might be considered promising; however, data regarding their safety are still limited. Few piecies of evidence on the efficacy of histamine-2 receptor blockers and proton pump inhibitors in preterm infants with GER are currently available. Nevertheless, a significantly increased risk of necrotizing enterocolitis and infections has been largely reported in association with their use, thereby leading to an unfavorable risk-benefit ratio. The efficacy of metoclopramide inGER's improvement still needs to be clarified. Other prokinetic agents, such as domperidone and erythromycin, have been reported to be ineffective, whereas cisapride has been withdrawn due to its remarkable cardiac adverse effects. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of intravenous immunoglobulin (IVIg) and exchange transfusion (EXT) on rhesus haemolytic disease of the newborn (Rh-HDN) and evaluate treatment-related side effects. Methods: Retrospective chart review of two cohorts of newborns with Rh-HDN, treated with (Group 2) or without (Group 1) IVIg. Length of phototherapy, number of EXT, IVIg infusions, intrauterine and top-up red blood cells transfusions, need and permanence of umbilical venous catheter, and length of hospital stay, as well as treatment-related adverse events, were evaluated. Results: Charts of 88 newborns were reviewed (34 in Group 1, 54 in Group 2). Infants in Group 2 received a significantly lower number of EXT, had a lower risk of neurological impairment and needed an umbilical venous catheter for shorter, but required longer phototherapy, longer length of hospital stay, and more top-up transfusions. EXT was associated with a high number of adverse events. Two newborns treated with IVIg developed necrotizing enterocolitis (NEC). Conclusions: IVIg appear as an effective alternative to EXT, reducing the risk of neurological impairment and complications related to EXT. However, side effects of IVIg treatment (higher need of top-up transfusions and longer hospital stay) should be taken into account and the risk of NEC should be carefully monitored during treatment. [ABSTRACT FROM AUTHOR]

Background: Gastro-oesophageal reflux (GOR) is common in preterm infants; conservative interventions (i.e. dietary changes) should represent the first-line approach. Aim: To evaluate by combined pH and impedance monitoring (pH-MII) the effect of a new preterm formula thickened with amylopectin (TPF) on GOR features in symptomatic preterm infants. Methods: Twenty-eight symptomatic preterm newborns underwent a 24-hour pH-MII; each baby received eight meals (four of TPF and four of a preterm formula [PF]). GOR indexes (number, acidity, duration and height of GORs) after TPF and PF meals were compared by Wilcoxon Signed Ranks Test. Viscosity of PF and TPF was measured. Results: TPF significantly decreased the number of acid GORs detected by pH-monitoring (TPF vs. PF: median 20 vs. 24.5, p = 0.009), while it had no influence on Reflux Index (RIpH), nor on acid and non-acid GOR indexes detected by MII, GOR physical features, and GOR height. TPF's viscosity was extremely higher than PF's, and further increased at pH 3 after the addition of pepsin. Conclusions: The new formula was found to reduce the number of acid GORs detected by pH-monitoring; it did not reduce neither total oesophageal acid exposure nor non-acid GORs. At present its extended clinical use cannot be recommended. [ABSTRACT FROM AUTHOR]

Abstract: Background: Apnoea of prematurity (AOP) frequently recurs in preterm infants. We have previously shown that a significant but variable proportion of AOP is induced by gastro-oesophageal reflux (GOR). Aim: The aim of this study is to evaluate the efficacy of sodium alginate in reducing the frequency of GOR-related AOP. Subjects: Twenty-eight preterm infants with AOP were studied by a six-hour recording of combined multichannel intraluminal impedance and pH monitoring and polysomnography, including two three-hour postprandial periods: sodium alginate was given after one single meal named as drug-given (DG) meal, while the other as drug-free (DF). Results: During 165h of registration, 715 apnoeas were recorded, 368 after-DG and 347 after-DF (p=.99); furthermore, 851 GOR episodes were detected, 315 after-DG and 536 after-DF (p=.001). No differences in the number of AOP were found between DG and DF. A significant reduction in the number of acid GORs and in acid exposure was found during DG, while the administration of sodium alginate didn''t influence non-acid GOR indexes. The frequency of GOR-related apnoeas didn''t differ between DG and DF. Discussion: Sodium alginate doesn''t reduce the total number of AOP nor GOR-related apnoeas. On the other hand, it reduces acid GOR features, while it had no effect on non-acid GOR indexes. [Copyright &y& Elsevier]