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Introduction: Ohtahara syndrome (OS) is a rare drug-resistant epileptic encephalopathy characterized by frequent tonic spasms or focal motor seizures associated with the specific electroencephalographic pattern of burst suppression. It begins in the first months of life and represents less than 4% of childhood epilepsy cases. The prognosis depends from the aetiology and is generally poor with death in most cases during early childhood. The management of severe encephalopathies associated with OS is controversial, especially regarding the strategies to ensure the well-being of young patients and their families, requiring a continuous modulation of medical interventions: from the intensity of care waiting for the diagnosis, to palliative care where a prognosis of incurability, up to the possible desist from intensive/invasive treatments when they are no longer proportionate to the current clinical situation. Objective: Through the case of M, a 38-week-old newborn, intubated and mechanically ventilated since birth due to the absence of spontaneous respiratory activity, for whom the clinical diagnosis of OS was reached at about 4 months of life, we intend to investigate the related ethical issues: a. the proportionality and ethical-clinical appropriateness of treatments in patients for whom a poor prognosis quoad vitam is reached; b. the decision-making process to be shared with the parents, those were unable to accept the irreversibility of their daughter's illness, despite the psychological support offered to them from the beginning. Discussion: In a situation of probably irreversible pathology, such as severe encephalopathy with cortico-subcortical dysfunction and electrical-clinical picture of OS, associated with the absence of respiratory trigger, in which elements capable of modifying the prognosis quoad vitam do not emerge, and it is difficult for the parents to elaborate awareness about the seriousness of the disease, it becomes difficult to identify the limits

No abstract available

IMPORTANCE Repeated transfusions in preterm neonates with anemia of prematurity replace fetal hemoglobin (HbF) with adult Hb (HbA), which has a low oxygen affinity. The reduction of HbF is associated with a higher incidence of retinopathy of prematurity (ROP). OBJECTIVE To assess whether HbF and HbA are differently associated with cerebral tissue oxygenation in preterm neonates. DESIGN, SETTING, AND PARTICIPANTS This cohort study was a single-center, pilot study on cerebral oxygenation kinetics in preterm neonates with a gestational age between 24.0 weeks and 27.9 weeks who were admitted to the neonatal intensive care unit of Policlinico Universitario A. Gemelli IRCCS from December 27, 2021, to May 15, 2023. This study was ancillary to the ongoing, double-blind, multicenter Umbilical or Adult Donor Red Blood Cells in Extremely Low Gestational Age Neonates and Retinopathy of Prematurity (BORN) randomized clinical trial. The BORN trial outcome was ROP severity in neonates randomized to receive standard packed red blood cell (PRBC) transfusions obtained from RBCs of adult donors (A-RBCs) or from cord blood (CB-RBCs). According to standard procedures at the institute’s neonatal intensive care unit, patients concurrently received continuous cerebral near-infrared spectroscopy (NIRS) monitoring. This cohort study was not prespecified in the trial protocol. EXPOSURE Transfusion with A-RBCs or CB-RBCs. MAIN OUTCOMES AND MEASURES The main outcome was the kinetics of cerebral regional oxygen saturation (crSO2) and cerebral fraction of tissue oxygen extraction (cFTOE) associated with A-RBC or CB-RBC transfusions. Cerebral NIRS monitoring was performed by neonatologists and nurses, who were blinded to the PRBC type. The NIRS monitoring was conducted starting with the blood product order, during transfusion, and for the subsequent 24 hours after transfusion completion. The mean treatment effects of A-RBCs or CB-RBCs were quantified using a linear mixed model for repeated measure

ObjectiveTo evaluate whether acute histologic chorioamnionitis (HCA) diagnosed in the placenta may be associated with an increased occurrence of bronchopulmonary dysplasia (BPD) or death among extremely low gestational age neonates (ELGAN).MethodsThis Italian single-center case-control retrospective study involved ELGAN admitted to the neonatal intensive care unit between January 2019 and June 2022. Infants born from pregnant women with acute and severe HCA, identified as stage >= 2 and grade 2 HCA, (HCA-infants) were compared with infants of pregnant women without chorioamnionitis or with stage 1, grade 1 chorioamnionitis (no-HCA-infants).ResultsAmong 101 eligible ELGAN, 63 infants had complete clinical and histologic data relevant to the study: thirty infants were included in the HCA-infants group and 33 in the no-HCA-infants group. Neonatal and maternal demographic and clinical characteristics were similar between the two groups. Infants born from mothers with acute and severe HCA had significantly higher occurrence of composite BPD or death (18 [60%] vs. 9 [27%]; P = 0.012), as well as higher incidence of severe forms of BPD (6 [30%] vs. 2 [6%]; P = 0.045). In multiple logistic regression analysis, after adjustment for confounding covariates, HCA was an independent risk factor for BPD or death (OR, 4.49; 95% CI: 1.47-13.71).ConclusionsThis is the first study showing that in utero exposure to acute and severe HCA is an independent risk factor for the occurrence of composite BPD or death among ELGAN.Acute and severe histologic chorioamnionitis is an independent risk factor for the occurrence of bronchopulmonary dysplasia or death among extremely low gestational age neonates.

Sleep disorders are particularly important in the development of children, affecting the emotional, behavioural, and cognitive spheres. The incidence of these disorders has been assessed in different types of populations, including patients with a history of premature birth, who, from the literature data, would seem to have an increased incidence of sleep disorders at school age. The aims of the present study are: (i.) to assess the presence of sleep disorders in a population of very preterm infants at 6–36 months who are at low risk of neurological impairments using the Italian version of the Sleep Disturbance Scale for Children (SDSC) adapted for this age group, and (ii.) to identify possible differences from a control group of term-born infants. A total of 217 low-risk preterm and 129 typically developing infants and toddlers were included in the study. We found no differences in the SDSC total and the factor scores between these two populations of infants. Low-risk preterm infants and toddlers showed similar incidences of sleep disorders to their term-born peers. Further clinical assessments will be needed to confirm these data at school age.

Repeated red blood cell (RBC) transfusions in preterm neonates cause the progressive displacement of fetal hemoglobin (HbF) by adult hemoglobin. The ensuing increase of oxygen delivery may result at the cellular level in a dangerous condition of hyperoxia, explaining the association between low-HbF levels and retinopathy of prematurity or bronchopulmonary dysplasia. Transfusing preterm neonates with RBC concentrates obtained from allogeneic umbilical blood is a strategy to increase hemoglobin concentration without depleting the physiologic HbF reservoir. This review summarizes the mechanisms underlying a plausible beneficial impact of this strategy and reports clinical experience gathered so far in this field.

Background Spinal muscular atrophy (SMA) is due to the homozygous absence of SMN1 in around 97% of patients, independent of the severity (classically ranked into types I-III). The high genetic homogeneity, coupled with the excellent results of presymptomatic treatments of patients with each of the three disease-modifying therapies available, makes SMA one of the golden candidates to genetic newborn screening (NBS) (SMA-NBS). The implementation of SMA in NBS national programmes occurring in some countries is an arising new issue that the scientific community has to address. We report here the results of the first Italian SMA-NBS project and provide some proposals for updating the current molecular diagnostic scenario. Methods The screening test was performed by an in-house-developed qPCR assay, amplifying SMN1 and SMN2. Molecular prognosis was assessed on fresh blood samples. Results We found 15 patients/90885 newborns (incidence 1:6059) having the following SMN2 genotypes: 1 (one patient), 2 (eight patients), 2+c.859G>C variant (one patient), 3 (three patients), 4 (one patient) or 6 copies (one patient). Six patients (40%) showed signs suggestive of SMA at birth. We also discuss some unusual cases we found. Conclusion The molecular diagnosis of SMA needs to adapt to the new era of the disease with specific guidelines and standard operating procedures. In detail, SMA diagnosis should be felt as a true medical urgency due to therapeutic implications; SMN2 copy assessment needs to be standardised; commercially available tests need to be improved for higher SMN2 copies determination; and the SMN2 splicing-modifier variants should be routinely tested in SMA-NBS.

OBJECTIVE: THE EXTENT OF VERTICAL TRANSMISSION ( VT ) OF SARS-COV-2 FROM MOTHERS TO NEONATES IS STILL UNCERTAIN. WE AIMED TO DETERMINE THE INCIDENCE OF VT. STUDY DESIGN: IN THIS PROSPECTIVE COHORT STUDY ALL MOTHER DIAGNOSED WITH SARS-COV-2 INFECTION AT TIME OF DELIVERY OR UP TO ONE WEEK PRIOR AND THEIR NEONATE MANAGED IN A TERTIARY REFERRAL HOSPITAL FOR PREGNANCY COMPLICATED BY COVID-19 IN ROME, FROM APRIL 2 TO DECEMBER 22,2020,WERE INCLUDED.MATERNAL INFECTION WAS DEFINED AS NASOPHARYNGEAL SWAB TEST RESULTS POSITIVE FOR SARS-COV-2 RT-PCR. BIOLOGICAL SAMPLES WERE COLLECTED BEFORE, AT, AND AFTER DELIVERY TO TEST POSITIVITY FOR SARS-COV-2 RT-PCR AND ANTI SARS-COV-2 SPECIFIC ANTIBODIES. RESULTS: THE COHORT INCLUDED 95 WOMEN AND 96 NEONATES WITH DOCUMENTED SARS-COV-2 TEST RESULTS. FOUR NEONATES ( 4.2% ) TESTED POSITIVE. THE INCIDENCE OF VT, ACCORDING TO THE GUIDANCE CRITERIA FOR DIAGNOSING PERNATAL SARS-COV-2 INFECTION,WAS 5.2%. NEONATAL SYMPTOMS WERE DUE TO PREMATURITY OR FETAL DISTRESS: SYMPTOMATIC INFANTS HAD LOWER MEDIAN [ MIN-MAX ] GESTATIONAL AGE ( 38.1 [29.3-40.6] VS 39.3 [33.9-41.9] WEEKS ; P= .036), 1-MIN ( 9[3-9]VS 9[7-10]; P= .036), AND 5-MIN APGAR SCORES (10[6-10] VS 10[8-10]; P= .012) THAN ASYMPTOMATIC INFANTS, AND NEEDED MORE FREQUENTLY ASSISTANCE IN THE DELIVERY ROOM ( 22.2% VS 2.5%; P= .0089. ONLY 6(7.1%) NEONATES HAD ANTI SARS-COV-2 SPECIFIC ANTIBODIES,DESPITE THE ONGOING MATERNAL INFECTION. CONCLUSIONS: THE INCIDENCE OF VT IS LOW AS IS THE DETECTION OF SPECIFIC ANTI SARS-COV-2 ANTIBODIES IN CORD BLOOD WHEN INFECTION IS CONTRACTED LATE IN PREGNANCY.THIS WOULD SUGGEST POOR PROTECTION OF INFANTS AGAINST HORIZONTAL TRANSMISSION OF THE VIRUS

Late-preterm infants (LPT) are at increased risk for long-term neurodevelopmental sequelae and iron deficiency. The aim of the study is to assess the positive effect of iron supplementation on psychomotor development in healthy LPT. We designed a randomized placebo-controlled double-blind trial dividing the newborns into two groups. Every patient was assessed using the Griffiths Mental Development Scales (GMDS)-II edition at 12-month post-conceptional age. The study was performed at the Neonatology Unit of our Hospital, in Italy. Sixty-six healthy LPT infants born between -340/7 and -366/7 weeks of gestational age were enrolled in the study. One group received martial prophylaxis from the third week of life to 6 months of post-conceptional age (2 mg/kg/day of iron pidolate), the other received placebo. Fifty-two of the enrolled infants were assessed using the GMDS at 12-month of post-conceptional age. Statistical analysis of the mean scores of the Griffiths subscales was performed. There was a difference in the mean developmental quotient (DQ) (p < 0.01) between the two groups: iron group mean DQ 121.45 +/- 10.53 vs placebo group mean DQ 113.25 +/- 9.70. Moreover, mean scores of the Griffiths subscales A, B, and D showed significant differences between the two groups (scale A p < 0.05, scale B p < 0.02, scale D p < 0.01, respectively).Conclusions: We recommend that all LPT neonates receive iron supplementation during the first 6 months of life in order to improve their 1-year neurodevelopmental quotient.

Respiratory distress (RD) is one of the most common causes of admission to the neonatal intensive care unit. Correct diagnosis and timely intervention are crucial. Lung ultrasonography (LU) is a useful diagnostic tool for the neonatologist in the diagnosis of RD; the neonatal lung ultrasonography score (nLUS) can be used in the diagnostic process, but some authors hypothesise that it is also useful for the management of some neonatal RD. The aim of this study is to analyse the changes in nLUS score before (T0) and after (T1) the start of respiratory support with nasal CPAP in neonates over 32 weeks of age with RD. Thirty-three newborns were enrolled in this retrospective study. LU was performed before and after the start of CPAP. The median nLUS scores at T0 and T1 were 9 (IQR 7–12) and 7 (IQR 4–10), respectively, and showed a significant difference (p < 0.001). The magnitude of reduction in nLUS score, expressed as a percentage, was inversely related to the need for subsequent administration of exogenous surfactant. The study suggests the usefulness of the nLUS score in assessing the response to CPAP in neonates over 32 weeks gestational age.

Our aim was to develop a new module for assessing the floppy infant, to describe the application of the module in a cohort of low-risk newborns and piloting the module in a cohort of floppy infants. The module was applied to a cohort of 143 low-risk newborns and piloted in in a cohort of 24 floppy infants. The new add-on module includes a neurological section and provides a section for recording information obtained by physical examination and antenatal history. For each item, column 1 reports abnormal findings, column 3 normal findings, and column 2 intermediate signs to be followed. Consistent with previous studies, in low-risk infants, none had definitely abnormal or mildly abnormal signs, with the exception of tendon reflexes that were not easily elicitable in 17.14% of term-born infants. Conclusion: Our study suggest that the module can be easily used in a clinical setting as an add-on to the regular neonatal neurological examination in newborns identified as hypotonic on routine examination. Larger cohorts are needed to establish the accuracy of the prognostic value of the module in the differential diagnosis of floppy infant.What is Known:• Hypotonia is one of the key signs in newborns with neuromuscular disorders and can be associated with a wide range of other conditions (central nervous system involvement, genetic and metabolic diseases).• Weakness or/and contractures can identify infants with a neuromuscular disorder and help in the differential diagnosis of floppy infants.What is New:• To date, this is the first attempt to develop and apply a specific neurological module for the assessment of the floppy infant.• The module can be used in a routine clinical setting as an add-on to the regular neurological examination and has potential to differentiate the floppy infants from the low-risk infants.

The possibility to identify patients with spinal muscular atrophy through neonatal screenings has highlighted the need for clinical assessments that may systematically evaluate the possible presence of early neurological signs. The aim of this study was to use the Hammersmith Neonatal Neurological Examination (HNNE) and a module specifically designed for floppy infants to assess the possible variability of neurological findings in infants identified through neonatal screening. The infants included in this study were identified as part of a pilot study exploring neonatal screening in two Italian regions. A neurological examination was performed using the HNNE and an additional module developed for the assessment of floppy infants. Seventeen infants were identified through the screening. One patient had 1 SMN2 copy, 9 had 2 copies, 3 had 3, and 4 had more than 3 copies. Nine of the 17 infants (53%) had completely normal results on both scales, 3 had minimal signs, and the other 5 had more obvious clinical signs. The number of SMN2 copies was related to the presence of abnormal neurological signs (p = 0.036) but two SMN2 copies were associated with variable clinical signs as they were found in some infants with respectively normal examination or obvious severe early signs. Conclusions: Our results suggest that the combination of both scales increases the possibility to detect neonatal neurological signs and to define different early patterns of involvement also identifying paucisymptomatic patients.What is Known:• The use of new therapeutic options in presymptomatic SMA patients leads to a dramatic reduction of the onset and severity of the diesease.• The already existing tools commonly used in Type I SMA (HINE and CHOP-intend) may not be suitable to identify minor neurological signs in the neonatal period.What is New:• Combining the HNNE and the floppy infant module, we were able to identify early neurological signs in SMA infants identified through newborn screening&

Background: Spinal muscular atrophy (SMA) is due to the homozygous absence of SMN1 in around 97% of patients, independent of the severity (classically ranked into types I-III). The high genetic homogeneity, coupled with the excellent results of presymptomatic treatments of patients with each of the three disease-modifying therapies available, makes SMA one of the golden candidates to genetic newborn screening (NBS) (SMA-NBS). The implementation of SMA in NBS national programmes occurring in some countries is an arising new issue that the scientific community has to address. We report here the results of the first Italian SMA-NBS project and provide some proposals for updating the current molecular diagnostic scenario. Methods: The screening test was performed by an in-house-developed qPCR assay, amplifying SMN1 and SMN2. Molecular prognosis was assessed on fresh blood samples. Results: We found 15 patients/90885 newborns (incidence 1:6059) having the following SMN2 genotypes: 1 (one patient), 2 (eight patients), 2+c.859G>C variant (one patient), 3 (three patients), 4 (one patient) or 6 copies (one patient). Six patients (40%) showed signs suggestive of SMA at birth. We also discuss some unusual cases we found. Conclusion: The molecular diagnosis of SMA needs to adapt to the new era of the disease with specific guidelines and standard operating procedures. In detail, SMA diagnosis should be felt as a true medical urgency due to therapeutic implications; SMN2 copy assessment needs to be standardised; commercially available tests need to be improved for higher SMN2 copies determination; and the SMN2 splicing-modifier variants should be routinely tested in SMA-NBS. Keywords: Genetic Testing; Genetics, Population; Neonatal Screening; Neuromuscular Diseases.

The long-term outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are still unknown. We performed a single-center, prospective, observational study of newborns born from mothers with microbiologically confirmed SARS-CoV-2 infection in pregnancy or at time of delivery. Infants were offered a multidisciplinary follow-up consisting of nasopharyngeal Polymerase Chain Reaction test at birth and at 48–72 h of life, auxological growth and neurological development, serologic testing, and audiological and ophthalmological assessments. One-hundred ninety-eight mothers and 199 newborns were enrolled. Of the 199 newborns, 171 underwent nasopharyngeal swab, four (2.3%) and two (1.15%) children tested positive at birth and 48–72 h of life, respectively. None had SARS-CoV-2 related symptoms. Auxologic and neurologic development were normal in all children during follow-up. Nine out of 59 infants had SARS-CoV-2 IgG at 3 months of life, which was associated with a positive nasopharyngeal swab at birth (P = 0.04). Twenty seven out of 143 (18.8%) newborns had pathologic transitory evoked otoacoustic emissions at birth, although 14/27 repeated after 1 month were normal. Audiological evaluation was completed with Auditory Brainstem Response between the third and sixth month of life in 34 children, showing in all normal hearing threshold. The ophthalmological evaluation found retinal vascular anomalies in 3/20 (15%) children, immature visual acuity in 5/20 (25%) children, and reduced distance attention in 6/20 cases (30%). Conclusions: Our study showed that the neonatal and mid-term multidisciplinary outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are mostly positive, with the exception of ophthalmologic findings which, in a preliminary cohort, were abnormal in about 15% of cases. Further prospective, longitudinal studies are needed to better understand the clinical outcomes of

Objective: The aim of this study is to assess the impact of the COVID-19 pandemic on mental health, type of delivery, and neonatal feeding of pregnant women with or without SARS-CoV-2 infection during gestation. Study Design: The study was conducted online, and anonymous survey was distributed to mothers that delivered during the COVID-19 pandemic. Results: The survey was completed by 286 women, and 64 women (22.4%) had COVID-19 during pregnancy. Women that had SARS-CoV-2 infection during pregnancy or at time of delivery had a significantly higher probability of being separated from the newborn (p < 0.0001) and a significantly lower probability of breastfeeding (p < 0.0001). The Edinburg Postnatal Depression Scale, to assess if mothers had symptoms of postnatal depression, showed that items suggestive of postnatal depression were relatively frequent in the whole cohort. However, women with SARS-CoV-2 infection during pregnancy reported higher probability of responses suggestive of postnatal depression in eight out of 10 items, with statistically significant differences in three items. Conclusion: The COVID-19 pandemic affected the type of delivery and breastfeeding of pregnant women, particularly when they had SARS-CoV-2 infection. This, in turn, had an impact on the psychological status of the interviewed mothers, aspects that could benefit of special support.

Aim: We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify cognitive performance delay at 2 years in a large cohort of infants born at term. Method: We conducted a retrospective study of infants born at term at risk of neurodevelopmental impairments assessed using the HINE between 3 and 12 months post-term age and compared them with a cohort of typically developing infants born at term. All infants performed a neurodevelopmental assessment at 2 years of age using the Mental Development Index (MDI) of the Bayley Scales of Infant Development, Second Edition; the presence of cerebral palsy (CP) was also reported. The infants were classified as being cognitively normal/mildly delayed or significantly delayed (MDI < 70). The predictive validity of HINE scores for significantly delayed cognitive performance, in infants with and without CP, was calculated using specific cut-off scores according to age at assessment. Results: A total of 446 at-risk and 235 typically developing infants (345 males, 336 females; mean [SD] gestational age 38.7 weeks [1.4], range 25–36 weeks) were included. Of the at-risk infants, 408 did not have CP at 2 years; 243 had a normal/mild delayed MDI and 165 had an MDI less than 70. Of the at-risk infants, 38 developed CP. HINE scores showed a good sensitivity and specificity, mainly after 3 months, for identifying significantly delayed cognitive performance in infants without CP. In those with CP, the score was associated with their cognitive performance. The comparison group had the highest HINE scores. Interpretation: The HINE provides evidence about the risk of delayed cognitive performance at age 2 years in infants born at term with and without CP.

Aim: To describe the profile of global and single items of the Hammersmith Infant Neurological Examination (HINE) in a population of low-risk infants born very preterm during the first year of life. Method: The HINE was performed at 3, 6, 9, and 12 months’ corrected age in a population of low-risk infants born preterm with a gestational age of fewer than 32 weeks and with normal or minimal changes on neuroimaging. Results: A total of 174 infants born preterm (96 males, 78 females; mean gestational age = 27 weeks [SD = 1.8], range 23–31 weeks) fulfilled the inclusion criteria. The 10th centile cut-off score with median and range was reported for the HINE global and subsection scores. A progressive increase in global HINE scores was observed. Most of the single items, especially those related to tone, posture, and reflexes, showed progressive maturation. Interpretation: Our results, which provide longitudinal data for single-item and global scores in a population of low-risk infants born very preterm, can be used as a reference in both clinical and research settings to monitor early neurological signs in these infants. These data could be used as normative data when examining low-risk infants born preterm.

Introduction: Ureaplasma (U.) and Mycoplasma (M.) species have been related to pregnancy complications (including preterm birth) and worse neonatal outcomes. The aim of our work is to evaluate neurodevelopmental outcomes in preterm infants born to mothers with Ureaplasma/Mycoplasma colonization during pregnancy. Methods: Preterm infants with gestational age (GA) of ≤ 30 weeks were included in a retrospective follow-up study. To evaluate the effects of maternal vaginal colonization, we divided preterm infants into two groups: exposed and unexposed infants. All infants were assessed at 24 ± 3 months of age using Griffith's Mental Developmental Scales (GMDS). Results: Among 254 preterm infants, only 32 infants (12.6%) were exposed to U. /M. colonization during pregnancy. Exposed infants and unexposed ones had a similar Griffith's Developmental Quotient (106 ± 27.2 vs. 108.9 ± 19.5, respectively), without significant differences (p = 0.46). However, exposed infants had a significantly poorer outcome than their unexposed peers in terms of locomotor abilities (100.7 ± 28.3 exposed vs. 111.5 ± 26.1 unexposed, p = 0.03). Conclusion: For visual and hearing impairment, exposed and unexposed infants had similar incidences of cognitive and motor impairment. However, exposed infants had significantly lower locomotor scores than unexposed peers. Keywords: cognitive; motor outcomes; motor performance; neonate; neurodevelopment; newborn; pregnant; prematurity—risk assessment and prevention.

The study investigates the role of the oxidative and proteolytic inactivation of alpha-1 antitrypsin (AAT) in the pathogenesis of bronchopulmonary dysplasia (BPD) in premature infants. Bronchoalveolar lavage fluid (BALF) samples were collected on the 3rd day of life from mechanically ventilated neonates with gestational age ≤ 30 weeks and analyzed without previous treatment (top-down proteomics) by reverse-phase high-performance liquid chromatography-electrospray ionization mass spectrometry. AAT fragments were identified by high-resolution LTQ Orbitrap XL experiments and the relative abundances determined by considering the extracted ion current (XIC) peak area. Forty preterm neonates were studied: 20 (50%) did not develop BPD (no-BPD group), 17 (42.5%) developed mild or moderate new-BPD (mild + moderate BPD group), and 3 (7.5%) developed severe new-BPD (severe BPD group). Eighteen fragments of AAT and a fragment of AAT oxidized at a methionine residue were identified: significantly higher values of AAT fragments 25–57, 375–418, 397–418, 144–171, and 397–418 with oxidized methionine were found in the severe BPD group. The significantly higher levels of several AAT fragments and of the fragment 397–418, oxidized in BALF of preterm infants developing BPD, underlie the central role of an imbalance between proteases and protease inhibitors in exacerbating lung injury and inducing most severe forms of BPD. The study has some limitations, and between them, the small sample size implies the need for further confirmation by larger studies.

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Background: Few studies evaluated the efficacy of pharmacological therapy for gastro-esophageal reflux disease (GERD) in newborns, whose safety has been questioned. Esophageal basal impedance (BI) is a marker of mucosal integrity, and treatment with proton pump inhibitors significantly increases BI in infants; however, no correlation with clinical improvement was reported.Aims: To evaluate the relationship between BI and other esophageal pH-impedance parameters and clinical response to therapy in newborns with GERD.Study design: Multicenter retrospective study.Subjects: Infants who received omeprazole or ranitidine for GERD.Outcome measures: Complete response to therapy was defined as symptom decrease by >= 50% compared to baseline, partial response as symptom decrease <50%, no response as no symptom decrease based on chart analysis. Response to therapy was assessed 2 and 4 weeks after the onset of therapy. Univariate and multivariate statistics were performed to assess associations between response to therapy and clinical/pH-impedance parameters.Results: We studied 60 infants (51 born preterm): 47 received omeprazole, 13 ranitidine. Response to therapy was associated with decreasing esophageal clearance time: odds ratio 0.308, 95%CI 0.126-0.753, p = 0.010 at 2 weeks, odds ratio 0.461, 95%CI 0.223-0.955, p = 0.037 at 4 weeks.Conclusions: Clinical response to therapy among infants with GERD was associated with esophageal clearance but not with esophageal BI level.

Aim: Extra-uterine Growth Restriction (EUGR) is common among preterm infants. Two types of EUGR definitions are still now available: cross-sectional definitions and longitudinal ones. In a cohort of very preterm infants, we aimed to evaluate which definition could better predict neurodevelopmental outcomes at 2 years of corrected age. We used Italian Neonatal Study Charts (INeS) growth charts and INTERGROWTH-21st (IG-21) standard charts and compared results. Method: We restrospectively collected data from clinical charts of 324 preterm newborns with a gestational age ≤30 weeks born from 2012 to 2017. Then we compared forty-eight definitions (24 cross-sectional and 24 longitudinal) of EUGR, in term of neurodevelopmental outcomes at 2 years of corrected age. Results: We included in the study 254 preterm infants, whose clinical information met the enrolment criteria. Nineteen out of 48 definitions of EUGR were significantly predictive both for Griffith's Development Quotient (GDQ) and Neurodevelopment Impairment (NDI). Among these, longitudinal definitions appeared to have a higher negative predictive value for NDI than cross-sectional ones. Furthermore, infants with EUGR appeared to have a lower cognitive score than their peers without EUGR. Interpretation: A loss of Zs > 1 SDS in weight and head circumference, calculated from when physiological weight loss is over and identified as soon as possible rather than at discharge, better predicts neurodevelopmental outcomes of preterm infants.

No abstract available

Background: Tactile maneuvers stimulating spontaneous respiratory activity in preterm infants are recommended since birth, but data on how and how often these maneuvers are applied in clinical practice are unknown. In the last years, most preterm newborns with respiratory failure are preferentially managed with non-invasive respiratory support and by stimulating spontaneous respiratory activity from the delivery room and in neonatal intensive care unit (NICU), in order to avoid the risks of intubation and prolonged mechanical ventilation. Methods: Preterm infants with gestational age < 31 weeks not intubated in the delivery room and requiring non-invasive respiratory support at birth will be eligible for the study. They will be randomized and allocated to one of two treatment groups: (1) the study group infants will be subject to the technique of respiratory facilitation within the first 24 h of life, according to the reflex stimulations, by the physiotherapist. The newborn is placed in supine decubitus and a slight digital pressure is exerted on a hemithorax. The respiratory facilitation technique will be performed for about three minutes and repeated for a total of 4/6 times in sequence, three times a day until spontaneous respiratory activity is achieved; thus, no respiratory support is required; (2) the control group infants will take part exclusively in the individualized postural care program. They will perform the technique of respiratory facilitation and autogenous drainage. Objective: To evaluate the efficacy of early respiratory physiotherapy in reducing the incidence of intubation and mechanical ventilation in the first week of life (primary outcome). Discussion: The technique of respiratory facilitation is based on reflex stimulations, applied early to preterm infant. Slight digital pressure is exerted on a “trigger point” of each hemithorax, to stimulate the respiratory activity with subsequent increase of the ipsilateral pulmonary minute ventilation

Background: JAM3 gene, located on human chromosome 11q25, encodes a member of the junctional adhesion molecule (JAM) family. Mutations of this gene are associated with hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts (HDBSCC). Case report: Herein, we present a newborn male with a prenatal suspicion of bilateral cataracts but without fetal ultrasound findings of cortical malformations. He was postnatally diagnosed with a clinical picture of HDBSCC and Early-onset Developmental and Epileptic Encephalopathy (DEE), associated to a homozygous variant of JAM3 gene. Conclusion: Identification of this variant in affected individuals has implications for perinatal and postnatal management and genetic counseling. To the best of our knowledge, this is the first case reported of a child with a JAM3 variant in Italy, from a different ethnic background than the other reported children until now (Saudi Arabian, Turkish, Afghani, and Moroccan origin). JAM3 screening could be requested in prenatal diagnosis of fetal congenital cataracts and included in Next-Generation DNA Sequencing panels.

Background: Suspending ordinary care activities during the COVID-19 pandemic made it necessary to find alternative routes to comply with care recommendations not only for acute health needs but also for patients requiring follow-up and multidisciplinary visits. We present the ‘Contactless’ model, a comprehensive operational tool including a plurality of services delivered remotely, structured according to a complexity gradient, aimed to cover diagnostic procedures and monitor disease progression in chronic pediatric patients. Methods: A multidisciplinary and multiprofessional project team was recruited, in collaboration with patients’ associations, to map a panel of available Evidence-Based solutions and address individual needs in full respect of the concept of personalized medicine. The solutions include a number of services from videoconsultations to more structure videotraining sessions. Results: A modular framework made up of four three Macro-levels of complexity - Contactless Basic, Intermediate and Advanced - was displayed as an incremental set of services and operational planning establishing each phase, from factors influencing eligibility to the delivery of the most accurate and complex levels of care. Conclusion: The multimodal, multidisciplinary ‘Contactless’ model allowed the inclusion of all Units of our Pediatric Department and families with children with disability or complex chronic conditions. The strengths of this project rely on its replicability outside of pediatrics and in the limited resources needed to practically impact patients, caregivers and professionals involved in the process of care. Its implementation in the future may contribute to reduce the duration of hospital admissions, money and parental absence from work.

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No abstract available

We describe the case of a male newborn presenting with a prenatal diagnosis of persistent hyperextension of the fetal neck and severe hypotonia and respiratory insufficiency at birth. Facial weakness, increased serum creatine kinase levels, and abnormal feeding, together with other signs, such as severe contractures, also classically associated with congenital myopathies prompted to perform a muscle biopsy showing internal rods suggestive of a possible nemaline myopathy. These findings suggest that a careful neurological examination should be performed in infants with persistent hyperextension of the fetal neck to exclude weakness and a possible underlying muscle disorder.

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Aim: We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify typical and delayed cognitive performance in a large population of infants born preterm, both with and without cerebral palsy (CP). Method: We conducted a retrospective study of infants born preterm who had repeated HINEs between 3 and 12 months corrected age. At 2 years, cognition was assessed using the Mental Development Index (MDI; from the Bayley Scales of Infant Development, Second Edition) and the presence and severity of CP was determined. All children were classified as cognitively typical/mildly delayed or significantly delayed (MDI <70) and CP. The predictive validity of HINE scores for significantly delayed cognitive performance, in children with and without CP, was calculated using specific cut-off scores according to age at assessment. Results: Of 1229 eligible infants (gestational age 25–36wks, mean [SD] 34.9 [2.3]; 646 males, 583 females), 1108 did not develop CP, 891 had an MDI that was typical/mildly delayed, and 217 had an MDI less than 70. Of the 121 infants who developed CP, the MDI was typical in 28, mildly delayed in 27, and less than 70 in 66. HINE scores showed a good sensitivity and specificity, especially after 3 months, for detecting significantly delayed cognitive performance in infants without CP. In those who developed CP, the score was associated with their cognitive level. Interpretation: The HINE provides information about the risk of delayed cognitive performance in infants born preterm with and without CP.

The original article [1] contains two errors in Fig. 1: 1) Fig. 1A mistakenly shows a tracheoesophageal fistula instead of the intended image of a tracheal agenesis. 2) There is a small omission in Fig. 1C whereby arrows intended to annotate the image are missing. The correct versions of Figs. 1A and 1C can be viewed ahead in this correction article. (Figure Presented).

The unexpected outbreak of Corona Virus Disease 19 had several consequences worldwide and on the Italian Health System. We report our experience in the reorganization of our Pediatric Department to prevent the risk of infection for both children and staff. We strongly believe that the need to face an unpredictable emergency situation should not affect the quality of the assistance to the non-Corona Virus Disease patients.

Background: Tracheal agenesis (TA) is a rare disorder usually diagnosed prenatally when a congenital high airway obstruction syndrome (CHAOS) is identified. We present a case of unexpected TA in a neonate without prenatal diagnosis of airway obstruction, with a difficult management at birth. Moreover, we discuss about differential diagnosis, classification and treatment issues. Case presentation: A 2280 g female neonate was born at 35 week gestational age (GA) with prenatal diagnosis of aortic coarctation, polyhydramnios and diffuse hyperechogenicity of the right lung. At birth, the neonate had no audible cry, no air entry to the lungs, and hypotonia. Tracheal intubation was unsuccessful, and no visualization of the trachea was obtained when tracheostomy was attempted. Post-mortem examination showed tracheal agenesis associated with tracheoesophageal fistula and revealed no cardiologic malformations. Aortic coarctation had been suspected prenatally because of the first portion of the descendent thoracic aorta being compressed by a fibrous band connecting the proximal and distal tracheal branches. CHAOS had not developed due to the tracheoesophageal fistula (TOF). Conclusions: TA is not always diagnosed in the fetus and it may present unexpectedly making the neonate's management at birth critical. An effective rescue temporary oxygenation may be obtained with mask ventilation or oesophageal intubation in those cases of TA associated with a TOF. We suggest to consider a fetal magnetic resonance imaging (MRI) when the association polyhydramnios/lung hyperechogenicity occurs, even in the absence of CHAOS or other malformations. Once a diagnosis is provided, the mother should be transferred to selected centres where an ex-utero intrapartum procedure (EXIT) can be attempted. Moreover, despite high mortality, different surgical management are described to improve survival.

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Our aim was to assess the efficacy and safety of intravenous (i.v.) paracetamol vs. i.v. ibuprofen for the treatment of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. This is a multicenter randomized controlled study. Infants with a gestational age of 25+0–31+6 weeks were randomized to receive i.v. paracetamol (15 mg/kg/6 h for 3 days) or i.v. ibuprofen (10-5-5 mg/kg/day). The primary outcome was the closure rate of hsPDA after the first treatment course with paracetamol or ibuprofen. Secondary outcomes included the constriction rate of hsPDA, the re-opening rate, and the need for surgical closure. Fifty-two and 49 infants received paracetamol or ibuprofen, respectively. Paracetamol was less effective in closing hsPDA than ibuprofen (52 vs. 78%; P = 0.026), but the constriction rate of the ductus was similar (81 vs. 90%; P = 0.202), as confirmed by logistic regression analysis. The re-opening rate, the need for surgical closure, and the occurrence of adverse effects were also similar. Conclusions: Intravenous paracetamol was less effective in closing hsPDA than ibuprofen, but due to a similar constriction effect, its use was associated with the same hsPDA outcome. These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA. Trial registration:Clinicaltrials.gov: NCT02422966, Date of registration: 04/09/2015; EudraCT no: 2013-003883-30.What is Known:• The successful closure of patent ductus arteriosus with oral paracetamol has been recently reported in several preterm infants, but only one randomized controlled study investigated the efficacy of intravenous paracetamol.What is New:• Intravenous paracetamol is less effective in closing hsPDA than ibuprofen, but have a similar constriction effect.• These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA.

Objective: To evaluate the course of fecal calprotectin (FC) in very preterm infants over the first 15 days of life in relation to the type of milk diet. Methods: This study was part of a randomized controlled trial comparing two different ways of integrating the own mother's milk (OMM) for the evaluation of feeding tolerance in very preterm infants. In infants with gestational age of ≤ 32 weeks randomized to receive preterm formula (PF group) or pasteurized donor human milk (PDHM group) as a supplement to the OMM insufficient or unavailable, FC level was planned to be measured at the first meconium passage and at days 8 and 15 of life (T0, T1, and T2, respectively). Results: FC data were available for all the 70 infants randomized, 35 in the PF group, and 35 in the PDHM group. The mean FC levels were similar in the two study groups at T0 and T1, whereas they were significantly higher in the PF group than the PDHM group at T2. FC values decreased over the first week of life in both groups and significantly increased over the second week of life only in the PF group. Conclusions: Our study demonstrates a significant increase in FC levels when PF is used as a supplement to the OMM compared to the use of PDHM. Further studies are needed to establish if the higher FC levels in infants receiving PF are the expression of a normal immunological maturation rather than an initial inflammatory process.

Repeated red blood cell (RBC) transfusions in preterm neonates are associated with poor outcome and increased risk for prematurity-associated diseases. RBC transfusions cause the progressive replacement of fetal haemoglobin (HbF) by adult haemoglobin (HbA). We monitored HbF levels in 25 preterm neonates until 36 weeks of post-menstrual age (PMA); patients received RBC units from allogeneic cord blood (cord-RBCs) or from adult donors (adult-RBCs), depending on whether cord-RBCs were available. Primary outcome was HbF level at PMA of 32 weeks. Twenty-three neonates survived until this age: 14 received no transfusions, two only cord-RBCs, three only adult-RBCs and four both RBC types. HbF levels in neonates transfused with cord-RBCs were significantly higher than in neonates receiving adult-RBCs (P < 0·0001) or both RBC types (P < 0·0001). Superimposable results were obtained at PMA of 36 weeks. Every adult-RBCs transfusion increased the risk for an HbF in the lowest quartile by about 10-fold, whereas this effect was not evident if combined adult- and cord-RBCs were evaluated. Overall, these data show that transfusing cord-RBCs can limit the HbF depletion caused by conventional RBC transfusions. Transfusing cord blood warrants investigation in randomised trials as a strategy to mitigate the severity of retinopathy of prematurity (NCT03764813).

Background: Retinopathy of prematurity (ROP) is often associated with visual impairment and multiple developmental disabilities. Aims: As most of the previous studies include infants with brain lesions, that can determine visual impairment per se, a cohort of low neurological risk preterm infants without ROP and with various degree of severity of ROP was assessed in order to establish visual and neurodevelopmental outcome. Study design: Preterm infants born at <31 weeks gestation, without major brain lesions, underwent visual function assessment at 1 year corrected age and neurodevelopmental assessment at 2 years corrected age. Subjects: One hundred and five infants were included in the study: 42 infants did not develop ROP, 7 reached stage 1 in zone 2 ROP, 37 reached prethreshold (untreated) type 2 ROP. The remaining 19 infants were classified as type 1 ROP. Outcome measures: Visual function (including fixing, tracking, visual acuity, visual field, attention at distance and nystagmus) were assessed at 12 months corrected age and Griffiths Scales at 2 years corrected age. Results: The severity of ROP was strongly correlated (p < 0.001) with both visual function at 1 year and neurodevelopment at 2 years. Similarly, the presence of nystagmus was also strongly correlated with visual and neurodevelopmental sequelae. Conclusions: Infants with no or milder retinopathy showed normal visual function at 1 year and neurodevelopment at 2 years. Infants who underwent treatment more frequently showed abnormal results on several aspects of visual function. Presence of nystagmus appeared to increase the risk for abnormal visual function and neurodevelopmental outcome.

Objective: Central venous access in critically ill newborns can be challenging. Ultrasound-guided brachio-cephalic vein catheterization is a relatively new procedure, recently introduced in several neonatal intensive care units. The aim of this study is to evaluate the safety and feasibility of such a technique in preterm babies. Design: Retrospective analysis of prospectively collected data on ultrasound-guided central venous catheter insertion in preterm neonates. Setting: Neonatal intensive care unit. Patients: Critically ill preterm neonates with weight below 1500 g requiring a central access. Interventions: Ultrasound-guided brachio-cephalic vein catheterization. Main Results: Thirty centrally inserted catheters were placed in 30 neonates. The success rate of the procedure was 100%. No case of accidental arterial or pleural puncture was registered during the study period. Conclusion: The brachio-cephalic vein can be safely catheterized in preterm newborns requiring intensive care after appropriate training.

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Background: The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E]). Methods: We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766. Findings: Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57–0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7–135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (

Neonatal causes of fever are a major source of concern for clinicians. If fever is combined with organ-specific sterile inflammatory manifestations the suspicion of autoinflammatory disorders should be considered, and the list of such conditions starting in the neonatal period includes chronic infantile neurological cutaneous articular syndrome, mevalonate kinase deficiency, deficiency of the interleukin-1 receptor antagonist, otulipenia, STING-associated vasculopathy with onset in infancy and Blau syndrome. Other causes of noninfectious fever that can rarely occur in newborns are Kawasaki disease, Behçet’s disease, and hemophagocytic lymphohistiocytosis. Diagnosis of these exceptionally rare disorders is challenging for neonatologists. An early recognition of these complex diseases might lead to use more specific or rational drugs preventing permanent consequences. This review focuses on the rarest causes of fever occurring in the neonatal age with the aim of portraying many protean clinical pictures associated with fever and reviewing the potential available treatments.

Neonates and prematures are among the most transfused categories of patients. Adverse reactions due to transfusions, such as transfusion-transmitted infections, can affect the rest of their lives. In this systematic review, we revised the literature concerning transfusion-transmitted infection in neonates. We reported case-reports and case-series previously published and we integrated these data with our experience at local neonatal intensive care unit. Moreover, we illustrated strategies for mitigating transfusion-transmitted infections, including donor selection and testing, pathogen inactivation technologies and combined approaches, as for Cytomegalovirus infection, integrating leukoreduction and identification of seronegative donors.

A male infant affected by type 0 SMA with one copy of SMN2 received early treatment with Nusinersen at the age of 13 days. He showed mild motor improvement 2 months after treatment started but despite also showing some minimal respiratory improvement, required tracheostomy at the age of 4 months and had increasing cardiac and autonomic dysfunction leading to exitus at 5 months. Our findings, expanding the results available on Nusinersen, confirm its relative efficacy in the most severely affected infants and provide clinical evidence to be used at the time requests for treating severe infants are discussed.

Objective To date, no information on late-onset infection in newborns to mother with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contracted in pregnancy are available. This study aimed to evaluate postdischarge SARS-CoV-2 status of newborns to mothers with COVID-19 in pregnancy that, at birth, were negative to SARS-CoV-2. Study Design This is an observational study of neonates born to mothers with coronavirus disease 2019 (COVID-19). Results Seven pregnant women with documented SARS-CoV-2 infection have been evaluated in our institution. One woman had a spontaneous abortion at 8 weeks of gestational age, four women recovered and are still in follow-up, and two women delivered. Two newborns were enrolled in the study. At birth and 3 days of life, newborns were negative to SARS-CoV-2. At 2-week follow-up, one newborn tested positive although asymptomatic. Conclusion Our findings highlight the importance of follow-up of newborns to mothers with COVID-19 in pregnancy, since they remain at risk of contracting the infection in the early period of life and long-term consequences are still unknown. Key Points Newborns to mothers with coronavirus disease 2019 (COVID-19) in pregnancy can acquire the infection later after birth. Newborns to mothers with COVID-19 in pregnancy need a long-term follow-up, even if they tested negative at birth. Specific guidelines for the long-term follow-up of newborns to mothers with COVID-19 in pregnancy are needed.

We detected SARS-CoV-2 RNA in multiple breastmilk samples that were collected and tested after the first lactation from a woman with a laboratory-confirmed Covid-19 diagnosis. We showed the potentiality of mother-to-child transmission by extra-respiratory routes. Thus, we believe that SARS-CoV-2 testing of breastmilk samples should became a common practice to prevent neonatal infections

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BACKGROUND: Term neonates (TN) are not routinely submitted to cranial ultrasound scan (CUS), since they are not considered at high risk for developing cerebral lesions. AIMS: To investigate the prevalence of cerebral abnormal findings in term neonates (TN), to identify the associated clinical features and to better target neonatal CUS investigations. STUDY DESIGN: Prospective observational study. SUBJECTS: A total number of 1805 healthy TN underwent CUS. 1181 neonates had clinical features supposed to increase the risk for cerebral abnormal findings (study cohort), 624 were controls. OUTCOME MEASURES: Prevalence of minimal, minor, and major cerebral abnormal findings was analyzed in six different categories of low-risk TN and compared to controls. RESULTS: Variations from normality at the neonatal CUS were observed in 402 TN (22.27%). In half of the cases the ultrasound findings were minimal abnormal findings, while minor abnormal findings were found in 179 TN (9.92%). About 1% of the studied neonates showed major cerebral abnormal findings potentially compromising neurodevelopmental outcome. The prevalence of the observed abnormal findings varied significantly in the different low-risk categories. CONCLUSIONS: The clinical features significantly increasing the risk for cerebral anomalies in healthy TN were microcrania, macrocrania, mild neurologic signs, and the detection of mild variations from normal cerebral aspect at the antenatal ultrasound evaluation