Publications by authors named "Andrea Dotta"

69 Publications

Growth and morbidity in infants with Congenital Diaphragmatic Hernia according to initial lung volume: A pilot study.

J Pediatr Surg 2021 Jul 8. Epub 2021 Jul 8.

Neonatal Surgery Unit, Medical and Surgical Department of Fetus - Newborn - Infant, "Bambino Gesù" Children's Hospital  IRCCS, Rome, Italy.

Background In congenital diaphragmatic hernia (CDH) survivors, failure to thrive is a well-known complication, ascribed to several factors. The impact of lung volume on growth of CDH survivors is poorly explored. Our aim was to evaluate if, in CDH survivors, lung volume (LV) after extubation correlates with growth at 12 and 24 months of life. Methods LV (measured as functional residual capacity-FRC) was evaluated by multibreath washout traces with an ultrasonic flowmeter and helium gas dilution technique, shortly after extubation. All CDH survivors are enrolled in a dedicated follow-up program. For the purpose of this study, we analyzed the correlation between FRC obtained shortly after extubation and anthropometric measurements at 12 and 24 months of age. We also compared growth between infants with normal lungs and those with hypoplasic lungs according to FRC values. A p < 0.05 was considered as statistically significant. Results We included in the study 22 CDH survivors who had FRC analyzed after extubation and auxological follow-up at 12 and 24 months of age. We found a significant correlation between FRC and weight Z-score at 12 months, weight Z-score at 24 months and height Z-score at 24 months. We also demonstrated that CDH infants with hypoplasic lungs had a significantly lower weight at 12 months and at 24 months and a significantly lower height at 24 months, when compared to infants with normal lungs. Conclusion We analyzed the predictive value of bedside measured lung volumes in a homogeneous cohort of CDH infants and demonstrated a significant correlation between FRC and growth at 12 and 24 months of age. An earlier identification of patients that will require an aggressive nutritional support (such as those with pulmonary hypoplasia) may help reducing the burden of failure to thrive.
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http://dx.doi.org/10.1016/j.jpedsurg.2021.06.013DOI Listing
July 2021

The Role of Lung Function Testing in Newborn Infants With Congenital Thoracic Arterial Anomalies.

Front Pediatr 2021 15;9:682551. Epub 2021 Jun 15.

Neonatal Intensive Care Unit, Medical and Surgical Department of Fetus, Newborn and Infant-"Bambino Gesù" Children's Hospital IRCCS, Rome, Italy.

Congenital thoracic arterial anomalies (CTAAs), such as complete or incomplete vascular rings, pulmonary artery sling, and innominate artery compression syndrome, may cause severe tracheomalacia and upper airway obstruction. An obstructive ventilatory pattern at lung function testing (LFT) has been suggested in the presence of CTAA. The severity of obstruction may be evaluated by LFT. Little is known about the use of LFT in newborn infants with CTAA. The aim of our study is to evaluate the role of LFT in CTAA diagnosis. This is a retrospective study, conducted between February 2016 and July 2020. All CTAA cases for whom LFT was performed preoperatively were considered for inclusion. Tidal volume (Vt), respiratory rate, and the ratio of time to reach the peak tidal expiratory flow over total expiratory time (tPTEF/tE) were assessed and compared to existing normative data. Demographics and CTAA characteristics were also collected. Thirty cases were included. All infants with CTAA showed a significantly reduced Vt and tPTEF/tE, compared to existing normative data suggesting an obstructive pattern. No significant differences were found for LFT between cases with a tracheal obstruction <50% compared to those with tracheal obstruction ≥50%, or between cases with and without symptoms. Sixteen infants (53.3%) had respiratory symptoms related to CTAA. Of these, only two cases had also dysphagia. LFT values were significantly reduced in cases with CTAA before surgery. LFT represents a potential feasible and non-invasive useful tool to guide diagnosis in the suspect of CTAA.
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http://dx.doi.org/10.3389/fped.2021.682551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239236PMC
June 2021

S100B protein, cerebral ultrasound and magnetic resonance imaging patterns in brain injured preterm infants.

Clin Chem Lab Med 2021 May 19. Epub 2021 May 19.

Department of Maternal, Fetal and Neonatal Medicine, ASO SS Antonio, Biagio and C. Arrigo, Alessandria, Italy.

Objectives: The early detection of preterm infants (PI) at risk for intraventricular hemorrhage (IVH) and neurological sequelae still constitutes an unsolved issue. We aimed at validating the role of S100B protein in the early diagnosis and prognosis of IVH in PI by means of cerebral ultrasound (CUS) and magnetic resonance imaging (MRI) today considered standard of care procedures.

Methods: We conducted an observational case-control study in 216 PI of whom 36 with IVH and 180 controls. Standard clinical, laboratory, radiological monitoring procedures and S100B urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth. Cerebral MRI was performed at 40-42 weeks of corrected gestational age.

Results: Elevated (p<0.001, for all) S100B levels were observed in the IVH group at all monitoring time-point particularly at first void when standard monitoring procedures were still silent or unavailable. S100B measured at first void correlated (p<0.001) with the grade of hemorrhage by means of CUS and with the site and extension of neurological lesion (p<0.001, for all) as assessed by MRI.

Conclusions: The present results showing a correlation among S100B and CUS and MRI offer additional support to the inclusion of the protein in clinical daily management of cases at risk for IVH and adverse neurological outcome. The findings open the way to further investigations in PI aimed at validating new neurobiomarkers by means of S100B.
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http://dx.doi.org/10.1515/cclm-2021-0278DOI Listing
May 2021

Severe herpes virus 6 interstitial pneumonia in an infant with three variants in genes predisposing to lung disease.

J Med Virol 2021 Aug 4;93(8):5182-5187. Epub 2021 May 4.

Neonatal Intensive Care Unit, Department of Medical and Surgical Neonatology, "Bambino Gesù" Children's Hospital IRCCS, Rome, Italy.

Infections due to human herpesvirus 6 (HHV-6) are frequent during early childhood. Usually, they have a favorable clinical course. Conversely, HHV-6 congenital infections occur in about 1% of neonates and may present with more severe clinical pictures. HHV-6 can be found in lung tissues and bronchoalveolar lavage (BAL) samples from patients with pneumonia and in immunocompromised patients can cause mild to severe pneumonia. In neonates, the role of HHV-6 in the genesis of severe pneumonia is poorly defined still now. We describe a healthy infant with a late-onset (15 days of life) severe interstitial pneumonia and heavy HHV-6 genome load, persistently detected in its BAL fluid. The baby underwent high-frequency oscillatory ventilation, hydroxychloroquine, steroids, and ganciclovir for 6 weeks and at 9 months she died. Next-generation sequencing of genes known to cause neonatal respiratory insufficiency revealed the presence of a "probably pathogenetic" heterozygous variant in the autosomal recessive DRC1 gene, a heterozygous variant of unknown significance (VUS) in the autosomal recessive RSPH9 gene, and a heterozygous VUS in the autosomal recessive MUC5B gene. HHV-6 infection should be considered in the differential diagnosis of late-onset severe respiratory distress in neonates and the co-occurrence of genetic predisposing factors or modifiers should be tested by specific molecular techniques. The intensity of HHV-6 genome load in BAL fluid could be an indicator of the response to antiviral therapy.
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http://dx.doi.org/10.1002/jmv.27016DOI Listing
August 2021

Invasive Infections in Neonates after Major Surgery: Current Evidence and New Directions.

Pathogens 2021 Mar 9;10(3). Epub 2021 Mar 9.

Neonatal Intensive Care Unit, Medical and Surgical Department of Fetus, Newborn and Infant, "Bambino Gesù" Children's Hospital IRCCS, 00165 Rome, Italy.

Infections represent a serious health problem in neonates. Invasive infections (ICIs) are still a leading cause of mortality and morbidity in neonatal intensive care units (NICUs). Infants hospitalized in NICUs are at high risk of ICIs, because of several risk factors: broad spectrum antibiotic treatments, central catheters and other invasive devices, fungal colonization, and impaired immune responses. In this review we summarize 19 published studies which provide the prevalence of previous surgery in neonates with invasive infections. We also provide an overview of risk factors for ICIs after major surgery, fungal colonization, and innate defense mechanisms against fungi, as well as the roles of different spp., the epidemiology and costs of ICIs, diagnosis of ICIs, and antifungal prophylaxis and treatment.
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http://dx.doi.org/10.3390/pathogens10030319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999498PMC
March 2021

Use of intravenous sodium bicarbonate in neonatal intensive care units in Italy: a nationwide survey.

Ital J Pediatr 2021 Mar 11;47(1):63. Epub 2021 Mar 11.

Neonatal Intensive Care Unit, Department of Neonatology, Bambino Gesù Children's Hospital, Rome, Italy.

Background: Metabolic Acidosis (MA) is a disturbance of the acid-base balance that can occur in preterm and critically ill term neonates due to different etiologies. Intravenous sodium bicarbonate (SB) has been traditionally used to correct such unbalance, despite the lack of evidence about its safety and efficacy. In literature, reported undesirable effects of treatment with SB in neonates include worsening of intracellular acidosis, impairment of myocardial function, cerebral blood flow fluctuations and intracranial hemorrhage. A national survey was conducted by the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology with the aim to assess and describe attitudes and practices concerning the use of SB, particularly for the treatment of MA in Italian NICUs.

Methods: A questionnaire regarding treatment of MA and SB prescription habits was sent to the directors of 120 Italian NICUs from June 2017 to March 2018.

Results: The survey response rate was 97.5% (117/120 centers). Findings showed that in 55% of the surveyed NICUs (64/117 units) it is common practice to correct MA with intravenous SB. On the other hand, the remaining 45% of the units try to solve the metabolic disturbances adopting different approaches (improving perfusion, adjusting ventilation parameters or increasing blood volume). Moreover, to prevent the occurrence of MA, 37.6% of the NICUs (44/117) include buffer salts (lactate, acetate or both) in parenteral nutrition prescriptions. SB is also used as a treatment for other conditions, mainly pathologies with bicarbonate loss and tubular acidosis (respectively in 53.8 and 32.5% of the NICUs).

Conclusion: This survey showed how SB is a commonly used treatment for MA in more than half of Italian NICUs, with indications and prescription criteria that significantly vary across centers. Based on current knowledge, it is reasonable to suggest that the management of neonatal MA should be firstly directed to identify the underlying disorders. Thus, the use of SB should be reserved only for selected cases, also considering the severity of SB adverse effects and the lack of evidence about its efficacy. Guidance for the management of MA is required to harmonize practices and reduce the use of potentially inappropriate and unsafe treatments.
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http://dx.doi.org/10.1186/s13052-021-00955-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953611PMC
March 2021

Could myocardial function be predictive of successful extubation in newborns and infants?

Pediatr Pulmonol 2021 Jun 23;56(6):1733-1738. Epub 2021 Feb 23.

Department of Medical and Surgical Neonatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Objective: To investigate the relationship between cardiac function and extubation readiness in infants using speckle tracking echocardiography.

Working Hypothesis: Cardiac function combined with established clinical parameters may better identify readiness for extubation.

Study Design: Pilot prospective observational study.

Patient Selection: Mechanically ventilated infants were included.

Methodology: Cardiac function was assessed by echocardiography immediately before extubation. Systolic and diastolic function in the left (LV) and right ventricles (RV) were assessed by measurement of longitudinal strain (LS), and circumferential strain (CS) in the LV only. Pulmonary artery pressures were assessed using the velocity of tricuspid regurgitation jet (TR), septal position, and end-systolic eccentricity index (EI ES). Cases who extubated successfully (Group 1) were compared to cases who required reintubation (Group 2).

Results: Twenty-five cases were included. LV CS and RV LS were significantly lower in those who required reintubation (Group 2) compared to those who were successfully extubated (Group 1) (LV CS, -21 (12)% vs. -33 (3)%, p = .001; RV LS -19 (2.7)% vs. -20 (2.5)%, p = .04). TR was absent in all cases. The septal shape was normal in 18 cases (72%), displaced to the left in 7 (28%) cases. No significant differences were found in LV EI ES between groups.
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http://dx.doi.org/10.1002/ppul.25316DOI Listing
June 2021

Biallelic hypomorphic variants in ALDH1A2 cause a novel lethal human multiple congenital anomaly syndrome encompassing diaphragmatic, pulmonary, and cardiovascular defects.

Hum Mutat 2021 May 1;42(5):506-519. Epub 2021 Apr 1.

Faculty of Health and Medical Sciences, Centre of Medical Research, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia.

This study shows a causal association between ALDH1A2 variants and a novel, severe multiple congenital anomaly syndrome in humans that is neonatally lethal due to associated pulmonary hypoplasia and respiratory failure. In two families, exome sequencing identified compound heterozygous missense variants in ALDH1A2. ALDH1A2 is involved in the conversion of retinol (vitamin A) into retinoic acid (RA), which is an essential regulator of diaphragm and cardiovascular formation during embryogenesis. Reduced RA causes cardiovascular, diaphragmatic, and associated pulmonary defects in several animal models, matching the phenotype observed in our patients. In silico protein modeling showed probable impairment of ALDH1A2 for three of the four substitutions. In vitro studies show a reduction of RA. Few pathogenic variants in genes encoding components of the retinoic signaling pathway have been described to date, likely due to embryonic lethality. Thus, this study contributes significantly to knowledge of the role of this pathway in human diaphragm and cardiovascular development and disease. Some clinical features in our patients are also observed in Fryns syndrome (MIM# 229850), syndromic microphthalmia 9 (MIM# 601186), and DiGeorge syndrome (MIM# 188400). Patients with similar clinical features who are genetically undiagnosed should be tested for recessive ALDH1A2-deficient malformation syndrome.
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http://dx.doi.org/10.1002/humu.24179DOI Listing
May 2021

High-Dose Micafungin in Neonates and Young Infants with Invasive Candidiasis: Results of a Phase 2 Study.

Antimicrob Agents Chemother 2021 03 18;65(4). Epub 2021 Mar 18.

Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.

Limited data are available on the most appropriate dosing, efficacy, and safety of micafungin in neonates and young infants with invasive candidiasis (IC). This study evaluated plasma levels, efficacy, and safety of micafungin at a dose of 8 mg/kg daily for a mean of 13.3 days (±5.2 days) in 35 neonates and young infants with IC. Micafungin plasma concentrations were 5.70 mg/liter preadministration and 17.23, 15.59, and 10.27 mg/liter after 1, 2, and 8 h, respectively. The resolution of the infection was achieved in 86.7% of patients treated for ≥14 days. In 20.0% of patients, we observed a transient hypertransaminasemia. Micafungin at a dose of 8 mg/kg daily is effective and well tolerated in neonates and young infants with IC. (This study has been registered at ClinicalTrials.gov under identifier NCT03421002 and in the EU Clinical Trials Register under number 2014-003087-20.).
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http://dx.doi.org/10.1128/AAC.02494-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097467PMC
March 2021

Correction to: Heart rate variability as possible marker of brain damage in neonates with hypoxic ischemic encephalopathy: a systematic review.

Eur J Pediatr 2021 May;180(5):1347

Pediatric Cardiology and Cardiac Arrhythmia/Syncope Complex Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, Rome, Italy.

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http://dx.doi.org/10.1007/s00431-020-03903-1DOI Listing
May 2021

A neonatal cluster of novel coronavirus disease 2019: clinical management and considerations.

Ital J Pediatr 2020 Dec 7;46(1):180. Epub 2020 Dec 7.

Pediatrics Unit, University Department of Pediatrics (DPUO), Bambino Gesù Children's Hospital - IRCCS, Via della Torre di Palidoro, 00050, Fiumicino, Rome, Italy.

Background: Lately, one of the major clinical and public health issues has been represented by Coronavirus disease of 2019 (COVID-19) during pregnancy and the risk of transmission of the infection from mother to child. Debate on perinatal management and postnatal care is still ongoing, principally questioning the option of the joint management of mother and child after birth and the safety of breastfeeding. According to the available reports, neonatal COVID-19 appears to have a horizontal transmission and seems to be paucisymptomatic or asymptomatic, compared to older age groups. The aim of this work is to describe a cluster of neonatal COVID-19 and discuss our experience, with reference to current evidence on postnatal care and perinatal management.

Methods: This is a retrospective observational case series of five mother-child dyads, who attended the Labor and Delivery Unit of a first-level hospital in Italy, in March 2020. Descriptive statistics for continuous variables consisted of number of observations, mean and the range of the minimum and maximum values.

Results: Five women and four neonates tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In one case, the mother-child dyad was separated and the neonate remained negative on two consecutive tests. Two positive neonates developed symptoms, with a predominant involvement of the gastrointestinal tract. Blood tests were unremarkable, except for a single patient who developed mild neutropenia. No complications occurred.

Conclusions: We agree that the decision on whether or not to separate a positive/suspected mother from her child should be made on an individual basis, taking into account the parent's will, clinical condition, hospital logistics and the local epidemiological situation. In conformity with literature, in our study, affected neonates were asymptomatic or paucisymptomatic. Despite these reassuring findings, a few cases of severe presentation in the neonatal population have been reported. Therefore, we agree on encouraging clinicians to monitor the neonates with a suspected or confirmed infection.
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http://dx.doi.org/10.1186/s13052-020-00947-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720265PMC
December 2020

Heart rate variability as possible marker of brain damage in neonates with hypoxic ischemic encephalopathy: a systematic review.

Eur J Pediatr 2021 May 27;180(5):1335-1345. Epub 2020 Nov 27.

Pediatric Cardiology and Cardiac Arrhythmia/Syncope Complex Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, Rome, Italy.

Heart rate variability (HRV) is currently considered the most valuable non-invasive test to investigate the autonomic nervous system function, based on the fact that fast fluctuations might specifically reflect changes of sympathetic and vagal activity. An association between abnormal values of HRV and brain impairment has been reported in the perinatal period, although data are still fragmentary. Considering such association, HRV has been suggested as a possible marker of brain damage also in case of hypoxic-ischemic encephalopathy following perinatal asphyxia. The aim of the present manuscript was to review systematically the current knowledge about the use of HRV as marker of cerebral injury in neonates suffering from hypoxic-ischemic encephalopathy. Findings reported in this paper were based on qualitative analysis of the reviewed data. Conclusion: A growing body of research supports the use of HRV as non-invasive, bedside tool for the monitoring of hypoxic-ischemic encephalopathy. The currently available data about the role of HRV as prognostic tool in case of hypoxic ischemic encephalopathy are promising but require further validation by future studies. What is Known: • Heart rate variability (HRV) is a non-invasive monitoring technique to assess the autonomic nervous system activity. • A correlation between abnormal HRV and cerebral injury has been reported in the perinatal period, and HRV has been suggested as possible marker of brain damage in case of hypoxic-ischemic encephalopathy. What is New: • HRV might provide precocious information about the entity of brain injury in asphyxiated neonates and be of help to design early, specific, and personalized treatments according to severity. • Further investigations are required to confirm these preliminary data.
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http://dx.doi.org/10.1007/s00431-020-03882-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691422PMC
May 2021

Universal Screening for SARS-CoV-2 of all Human Milk Bank Samples.

J Hum Lact 2021 02 22;37(1):40-42. Epub 2020 Sep 22.

9342 Neonatal Intensive Care Unit and Human Milk Bank, Medical and Surgical Department of Fetus - Newborn - Infant, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.

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http://dx.doi.org/10.1177/0890334420962074DOI Listing
February 2021

Therapeutic Drug Monitoring Is a Feasible Tool to Personalize Drug Administration in Neonates Using New Techniques: An Overview on the Pharmacokinetics and Pharmacodynamics in Neonatal Age.

Int J Mol Sci 2020 Aug 17;21(16). Epub 2020 Aug 17.

Neonatal Intensive Care Unit, Department of Medical and Surgical Neonatology, "Bambino Gesù" Children's Hospital IRCCS, 00165 Rome, Italy.

Therapeutic drug monitoring (TDM) should be adopted in all neonatal intensive care units (NICUs), where the most preterm and fragile babies are hospitalized and treated with many drugs, considering that organs and metabolic pathways undergo deep and progressive maturation processes after birth. Different developmental changes are involved in interindividual variability in response to drugs. A crucial point of TDM is the choice of the bioanalytical method and of the sample to use. TDM in neonates is primarily used for antibiotics, antifungals, and antiepileptic drugs in clinical practice. TDM appears to be particularly promising in specific populations: neonates who undergo therapeutic hypothermia or extracorporeal life support, preterm infants, infants who need a tailored dose of anticancer drugs. This review provides an overview of the latest advances in this field, showing options for a personalized therapy in newborns and infants.
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http://dx.doi.org/10.3390/ijms21165898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460644PMC
August 2020

Furosemide use in Italian neonatal intensive care units: a national survey.

Ital J Pediatr 2020 Jun 22;46(1):86. Epub 2020 Jun 22.

Indipendent researcher, Former director of Neonatal Intensive Care Unit, ASST Rhodense, Via C. Forlanini 95, 20024, Milan, Italy.

Background: Furosemide is approved in full term neonates to treat edema associated with congestive heart failure, cirrhosis and renal diseases. It is often administered off-label in premature neonates, to treat respiratory conditions and at doses greater-than-recommended. We conducted a national survey on behalf of the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology (SIN), to investigate its use in Italian neonatal intensive care units (NICUs), in conformity with current guidelines.

Methods: Between December 2016 and June 2017, a 14-item multiple-choice online questionnaire was sent to all NICU directors from the SIN directory. Gestational age, route of administration, posology, indications, referenced guidelines, adverse effects monitoring and the presence of Paediatric Cardiology or Cardiosurgery service on site were assessed. A chi-square test was performed 1) to evaluate differences in the distribution of responses between NICUs administering furosemide at doses higher-than-recommended; 2) to compare the proportion of NICUs administering furosemide at high doses in institutions with versus without a Paediatric Cardiology or Cardiosurgery service.

Results: The response rate was 50% (57/114). The intravenous and oral routes were chosen primarily; the intravenous administration in single doses predominated over continuous infusion. Its main therapeutic indications were congestive heart failure/overload (94.7%) and oligo-anuria (87.7%) however furosemide was also frequently used for broncopulmonary dysplasia (50.9%) and respiratory distress syndrome and/or transient tachypnea of the newborn (24.6%). In 28/57 NICUs furosemide was administered at doses higher-than-recommended. In most NICUs the same posology was used in term and preterm neonates. Compared to the total sample, a larger proportion of NICUs administering doses greater-than-recommended referenced current literature for reasons to do so (19.3 and 32.1% respectively). The presence of a Paediatric Cardiology or Cardiosurgery service on site did not correlate with the chosen posology. The majority of NICUs performed acoustic test and renal ultrasound for furosemide exposure greater than 2 weeks.

Conclusions: In Italian NICUs, furosemide is commonly prescribed to term and preterm newborns for label and unlabeled indications. Doses greater-than-recommended are frequently administered. Such use is not necessarily inappropriate. More research is required to assess the efficacy and safety of unlabeled use.
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http://dx.doi.org/10.1186/s13052-020-00851-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310123PMC
June 2020

Novel Coronavirus disease (COVID-19) in newborns and infants: what we know so far.

Ital J Pediatr 2020 Apr 29;46(1):56. Epub 2020 Apr 29.

Neonatal Intensive Care Unit, Department of Neonatology, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.

Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.
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http://dx.doi.org/10.1186/s13052-020-0820-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190200PMC
April 2020

Use of Disinfectant Wipes to Sanitize Milk's Containers of Human Milk Bank During COVID-19 Pandemic.

J Hum Lact 2020 08 23;36(3):547-549. Epub 2020 Apr 23.

Neonatal Intensive Care Unit and Human Milk Bank - Department of Medical and Surgical Neonatology, "Bambino Gesù" Children's Hospital IRCCS, Rome, Italy.

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http://dx.doi.org/10.1177/0890334420924639DOI Listing
August 2020

Managing COVID-19-Positive Maternal-Infant Dyads: An Italian Experience.

Breastfeed Med 2020 05 21;15(5):347-348. Epub 2020 Apr 21.

Department of Pediatrics, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy.

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http://dx.doi.org/10.1089/bfm.2020.0095DOI Listing
May 2020

Juvenile idiopathic arthritis in infants with Harlequin Ichthyosis: two cases report and literature review.

Ital J Pediatr 2020 Apr 15;46(1):44. Epub 2020 Apr 15.

Pediatric Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Background: Harlequin Ichthyosis is the most severe variant of congenital autosomal recessive ichthyosis, associated with severe morbidity and potentially lethal in early life. At birth, patients present thick and plaque-like scales all over the body, with consequent cutaneous and extra-cutaneous complications, such as poor thermoregulation, recurrent infections, pain, electrolytes imbalance and joint contractures. Juvenile Idiopathic Arthritis usually manifests before the age of 16 years and persists for more than 6 weeks. The association between these two pathologies has been described in the literature as a very rare event, which creates diagnostic and therapeutic challenge.

Case Presentation: We describe two patients affected by Harlequin Ichthyosis who early developed Juvenile Idiopathic Arthritis. Both patients were treated with retinoids, ibuprofen and long-acting intra-articular glucocorticoids; due to polyarticular involvement, one child was also treated with weekly oral methotrexate.

Conclusions: The association between Harlequin Ichthyosis and Juvenile Idiopathic Arthritis is rare and the pathophysiological mechanism that binds them is still unknown. Nonetheless caregivers should be aware of the possible occurrence of Juvenile Idiopathic Arthritis at very early ages in children affected by Harlequin Ichthyosis.
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http://dx.doi.org/10.1186/s13052-020-0817-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158043PMC
April 2020

Myocardial strain in newborn infants with tracheomalacia due to vascular rings, a pilot study.

J Matern Fetal Neonatal Med 2020 Feb 24:1-6. Epub 2020 Feb 24.

Department of Medical and Surgical Neonatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Vascular rings (VR) may cause severe tracheomalacia and upper airway obstruction (UAO). Increased pulmonary artery pressure and cardiac dysfunction have been described in patients with chronic UAO, but has not been investigated in infants with obstruction associated with VR. The aim of this study is to evaluate myocardial strain in infants with UAO due to VR. Demographic characteristics, respiratory symptoms, percentage of tracheal obstruction measured and classified using Computer Tomography, and lung function testing (LFT) were collected. Left (LV) and right ventricle (RV) systolic functions were measured using speckle tracking echocardiography longitudinal strain analysis (LS). Pulmonary artery pressure was evaluated using maximal tricuspid regurgitation jet velocity (TR) and LV end-systolic eccentricity index (EI). Fifteen cases were included in the study, six had mild tracheal obstruction (<50%), nine moderate-severe obstruction (≥50%). LV LS and RV LS were significantly reduced in cases with moderate to severe airway obstruction cases compared to those with mild airway obstruction (LV LS -15.9 versus -19.9%; RV LS -15.7 versus -20.5%,  = .04 and  = .02, respectively). Respiratory symptoms were more pronounced in moderate-severe cases. No significant differences in TR, EI, and LFT were observed. In cases of VR with severe tracheomalacia RV and LV myocardial strain is reduced, suggesting secondary cardiac dysfunction.
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http://dx.doi.org/10.1080/14767058.2020.1731457DOI Listing
February 2020

An omic approach to congenital diaphragmatic hernia: a pilot study of genomic, microRNA, and metabolomic profiling.

J Perinatol 2020 06 20;40(6):952-961. Epub 2020 Feb 20.

Division of Perinatal Medicine, Yale Child Health Research Center, Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.

Introduction: The omic approach can help identify a signature that can be potentially used as biomarkers in babies with congenital diaphragmatic hernia (CDH).

Objectives: To find a specific microRNA (miR) and metabolic fingerprint of the tracheal aspirates (TA) of CDH patients. We conducted a genetic analysis from blood samples.

Methods: TA samples collected in the first 48 h of life in patients with CDH, compared with age-matched controls. Metabolomics done by a mass spectroscopy-based assay. Genomics done using chromosomal microarray analysis.

Results: CDH (n = 17) and 16 control neonates enrolled. miR-16, miR-17, miR-18, miR-19b, and miR-20a had an increased expression, while miR-19a had a twofold decreased expression in CDH patients, compared with age-matched control patients. Specific metabolites separated neonates with CDH from controls. A genetic mutation found in a small subset of patients.

Conclusions: Specific patterns of metabolites and miR expression can be discerned in TA samples in infants with CDH.
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http://dx.doi.org/10.1038/s41372-020-0623-3DOI Listing
June 2020

The splice c.1815G>A variant in KIAA0586 results in a phenotype bridging short-rib-polydactyly and oral-facial-digital syndrome: A case report and literature review.

Medicine (Baltimore) 2020 Feb;99(8):e19169

Laboratory of Medical Genetics.

Introduction: KIAA0586 variants have been associated to short-rib thoracic dysplasia, an autosomal recessive skeletal ciliopathy characterized by a narrow thorax, short limbs, and radiological skeletal abnormalities.

Patient Concerns: Patients 1 and 2 were two Roma Gypsy siblings presenting thoracic dysplasia and a combination of oral cavity anomalies.

Diagnosis: A custom NGS gene panel, including genes associated to skeletal ciliopathies, identified the homozygous KIAA0586 splicing variant c.1815G>A (p.Gln605Gln) in both siblings, confirming the clinical diagnosis of short-rib-polydactyly.

Intervention: Patients were transferred to neonatal intensive care unit and received life-support treatment.

Outcomes: Patients 1 and 2 died after few hours and 1 month of birth, respectively, because of respiratory failure related with the disease.

Conclusion: We report two patients affected by short-rib polydactyly syndrome and overlapping phenotype with oral-facial-digital syndrome associated with the c.1815G>A variant in KIAA0586, suggesting a quite peculiar genotype-phenotype correlation.
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http://dx.doi.org/10.1097/MD.0000000000019169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034684PMC
February 2020

Breastfeeding Protection, Promotion, and Support in Humanitarian Emergencies: A Systematic Review of Literature.

J Hum Lact 2020 Nov 7;36(4):687-698. Epub 2020 Feb 7.

National Institute of Health, Rome, Italy.

Background: Infants, young children, and their mothers are vulnerable in humanitarian emergencies. The health benefits of optimal breastfeeding practices in emergency settings have been demonstrated by many researchers. guidelines illustrate a series of interventions to protect, promote, and support breastfeeding, but unfortunately, these recommendations are still scarcely applied.

Research Aims: (1) To review the literature describing the effectiveness of breastfeeding protection, promotion, and support interventions in humanitarian emergency contexts; (2) to describe the influence of interventions on breastfeeding initiation, exclusivity, and duration; and (3) to evaluate relevant mother and infant/child outcomes available in the literature.

Methods: PubMed, CINAHL, Cochrane Library, Psychology Database, JSTOR, Web of Science, EMBASE, and Ovid were searched for articles that examined breastfeeding protection, promotion, or support interventions and the resulting outcomes without any time limits ( = 10). Articles that did not include the interventions and related outcomes were excluded ( = 1,391).

Results: Improved breastfeeding outcomes were reported in four (40%) papers, and three (30%) highlighted a behavioral change in infant and young child feeding practices following the implementation of the interventions. Increased knowledge about appropriate infant and young child feeding practices among mothers and humanitarian/health staff was reported in eight (80%) papers. However, outcomes were sometimes only generically reported, and some of the included papers had a low strength of evidence.

Conclusion: In the literature, there is a great dearth of studies evaluating the influence of interventions aimed at improving breastfeeding in emergency settings. More evidence is urgently needed to encourage and implement optimal breastfeeding practices.
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http://dx.doi.org/10.1177/0890334419900151DOI Listing
November 2020

Fixed the gap, solved the problem? Eating skills in esophageal atresia patients at 3 years.

Dis Esophagus 2020 Jan;33(1)

Unit of Clinical Psychology, Department of Neuroscience and Neurorehabilitation, Bambino Gesù Children's Hospital, Rome, Italy.

Although eating problems have been described as long-term morbidities of esophageal atresia (EA), there have been few studies exploring eating outcomes in children born with EA as primary aim. Parents of children operated on for EA in our Institution from January 2012 to January 2016, answered a telephone structured interview developed specifically to conduct the present study, assessing eating skills at 3 years of age. Clinical data were collected from children's medical records. Parents (45 mothers and 6 fathers) of 51 children (male = 34; female = 17) with a median age of 3.5 years form the object of the study. Considering eating problems, parents reported that 23 children (45%) still have episodes of choking during meals at 3 years of age, 9 (45%) of these have more than one episode a week, and 19 parents (39%) reported higher levels of anxiety during mealtimes. Forty-four children (86%) were described by their parents as able to eat alone, 32 (65%) accepted all food textures and 45 (90%) was described as curious about food (3 years). Forty-three (86%) parents let their children eat with other people. Correlations showed that weaning age was significantly associated with number of dilatations (rs = 0.35, P = 0.012), days of mechanical ventilation (rs = 0.40, P < 0.001), and presence of gastrostomy tube at discharge (rs = 0.45, P < 0.001). Chewing age resulted associated with number of dilatations (rs = 0.34, P < 0.01) and days of mechanical ventilation (rs = 0.38, P < 0.01). Presence of choking episodes was associated with curiosity about food (rs = 0.29, P < 0.05), while frequent choking episodes were associated with higher parental anxiety during mealtimes (rs = 0.45, P < 0.05). In order to prevent delay in the achievement of eating developmental milestones in children operated on of EA, we advocate a dedicated preventive intervention from birth to follow-up.
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http://dx.doi.org/10.1093/dote/doz102DOI Listing
January 2020

Early predictors of perinatal brain damage: the role of neurobiomarkers.

Clin Chem Lab Med 2020 03;58(4):471-486

Neonatal Intensive Care Unit, G. d'Annunzio University, Chieti, Italy.

The early detection of perinatal brain damage in preterm and term newborns (i.e. intraventricular hemorrhage, periventricular leukomalacia and perinatal asphyxia) still constitute an unsolved issue. To date, despite technological improvement in standard perinatal monitoring procedures, decreasing the incidence of perinatal mortality, the perinatal morbidity pattern has a flat trend. Against this background, the measurement of brain constituents could be particularly useful in the early detection of cases at risk for short-/long-term brain injury. On this scenario, the main European and US international health-care institutions promoted perinatal clinical and experimental neuroprotection research projects aimed at validating and including a panel of biomarkers in the clinical guidelines. Although this is a promising attempt, there are several limitations that do not allow biomarkers to be included in standard monitoring procedures. The main limitations are: (i) the heterogeneity of neurological complications in the perinatal period, (ii) the small cohort sizes, (iii) the lack of multicenter investigations, (iv) the different techniques for neurobiomarkers assessment, (iv) the lack of consensus for the validation of assays in biological fluids such as urine and saliva, and (v), the lack of reference curves according to measurement technique and biological fluid. In the present review we offer an up-to-date overview of the most promising developments in the use of biomarkers in the perinatal period such as calcium binding proteins (S100B protein), vasoactive agents (adrenomedullin), brain biomarkers (activin A, neuron specific enolase, glial fibrillary acidic protein, ubiquitin carboxyl-terminal hydrolase-L1) and oxidative stress markers.
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http://dx.doi.org/10.1515/cclm-2019-0725DOI Listing
March 2020

Impact of the 2014 American Academy of Pediatrics recommendation and of the resulting limited financial coverage by the Italian Medicines Agency for palivizumab prophylaxis on the RSV-associated hospitalizations in preterm infants during the 2016-2017 epidemic season: a systematic review of seven Italian reports.

Ital J Pediatr 2019 Nov 9;45(1):139. Epub 2019 Nov 9.

Neonatology Unit, Academic Pediatric Department, Pediatric Hospital "Bambino Gesù", Rome, Italy.

Background: The only pharmacologic prophylaxis against respiratory syncytial virus (RSV) infection in preterm infants is the humanized monoclonal antibody palivizumab. After the 2014 modification of the American Academy of Pediatrics (AAP) recommendations, the Italian Medicines Agency (AIFA) limited the financial coverage for palivizumab prescriptions to otherwise healthy preterm infants with < 29 weeks of gestational age (wGA) aged < 12 months at the beginning of the 2016-2017 RSV season. However, due to the effect on disease severity and hospitalizations following this limitation, shown by several Italian clinical studies, in November 2017 AIFA reinstated the financial coverage for these infants. In this systematic review, we critically summarize the data that show the importance of palivizumab prophylaxis.

Methods: Data from six Italian pediatric institutes and the Italian Network of Pediatric Intensive Care Units (TIPNet) were retrieved from the literature and considered. The epidemiologic information for infants 29-36 wGA, aged < 12 months and admitted for viral-induced acute lower respiratory tract infection were retrospectively reviewed. RSV-associated hospitalizations were compared between the season with running limitation, i.e. 2016-2017, versus 2 seasons before (2014-2015 and 2015-2016) and one season after (2017-2018) the AIFA limitation.

Results: During the 2016-2017 RSV epidemic season, when the AIFA limited the financial coverage of palivizumab prophylaxis based on the 2014 AAP recommendation, the study reports on a higher incidences of RSV bronchiolitis and greater respiratory function impairment. During this season, we also found an increase in hospitalizations and admissions to the Pediatric Intensive Care Units and longer hospital stays, incurring higher healthcare costs. During the 2016-2017 epidemic season, an overall increase in the number of RSV bronchiolitis cases was also observed in infants born full term, suggesting that the decreased prophylaxis in preterm infants may have caused a wider infection diffusion in groups of infants not considered to be at risk.

Conclusions: The Italian results support the use of palivizumab prophylaxis for otherwise healthy preterm (29-36 wGA) infants aged < 6 months at the beginning of the RSV season.
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http://dx.doi.org/10.1186/s13052-019-0736-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842491PMC
November 2019

Expert consensus on palivizumab use for respiratory syncytial virus in developed countries.

Paediatr Respir Rev 2020 Feb 18;33:35-44. Epub 2018 Dec 18.

Neonatology Service, Hospital Clinic, Institut d'Investigacions Biomediques August Pi Suñer (IDIBAPS), Carrer del Rosselló 149, 08036 Barcelona, Spain. Electronic address:

Respiratory syncytial virus (RSV) infection is a leading cause of hospitalisation in early childhood and palivizumab is the only licensed intervention for prevention. Palivizumab guidelines should reflect the latest evidence, in addition to cost-effectiveness and healthcare budgetary considerations. RSV experts from Europe, Canada and Israel undertook a systematic review of the evidence over the last 5 years and developed recommendations regarding prophylaxis in industrialised countries. Almost 400 publications were reviewed. This group recommended palivizumab for: preterm infants (<29 and ≤31 weeks gestational age [wGA] and ≤9 and ≤6 months of age, respectively; high-risk 32-35wGA), former preterm children ≤24 months with chronic lung disease/bronchopulmonary dysplasia, children ≤24 months with significant congenital heart disease; and other high-risk populations, such as children ≤24 months with Down syndrome, pulmonary/neuromuscular disorders, immunocompromised, and cystic fibrosis. Up to 5 monthly doses should be administered over the RSV season. It is our impression that the adoption of these guidelines would help reduce the burden of RSV.
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http://dx.doi.org/10.1016/j.prrv.2018.12.001DOI Listing
February 2020

Monitoring the effectiveness of hypothermia in perinatal asphyxia infants by urinary S100B levels.

Clin Chem Lab Med 2019 06;57(7):1017-1025

Department of Maternal, Fetal and Neonatal Medicine, C. Arrigo Children's Hospital, Alessandria, Italy.

Background Perinatal asphyxia is a major cause of mortality and morbidity in neonates: The aim of the present study was to investigate, by means of longitudinal assessment of urinary S100B, the effectiveness of hypothermia, in infants complicated by perinatal asphyxia and hypoxic-ischemic encephalopathy. Methods We performed a retrospective case-control study in 108 asphyxiated infants, admitted to nine tertiary departments for neonatal intensive care from January 2004 to July 2017, of whom 54 underwent hypothermia treatment and 54 did not. The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120 h after birth. The results were correlated with the achievement of S100B levels within normal ranges at 72 h from hypothermia treatment. Routine laboratory parameters, longitudinal cerebral function monitoring, cerebral ultrasound and neurologic patterns were assessed according to standard protocols. Results Higher S100B concentrations were found in hypothermia-treated infants in both moderate (up to 12 h) and severe (up to 24 h) hypoxic-ischemic encephalopathy. S100B levels returned to normal ranges starting from 20 h of hypothermia treatment in moderate and from 36 h in severe hypoxic-ischemic encephalopathy. Conclusions The present results offer additional support to the usefulness of longitudinal neuro-biomarkers monitoring in asphyxiated infants treated by hypothermia. The pattern of S100B concentrations during hypothermia supports the need for further investigations aimed at reconsidering the time-window for patient recruitment and treatment, and the optimal duration of the cooling and rewarming phases of the hypothermia procedure.
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http://dx.doi.org/10.1515/cclm-2018-1094DOI Listing
June 2019

Lung Transplantation for Late-Onset Pulmonary Hypertension in a Patient with Congenital Diaphragmatic Hernia.

European J Pediatr Surg Rep 2018 Jan 26;6(1):e100-e103. Epub 2018 Dec 26.

Department of Neonatal Surgery, Bambino Gesù Children's Hospital, Rome, Italy.

Lung hypoplasia and pulmonary hypertension (PH) in association with congenital diaphragmatic hernia (CDH) may cause fatal respiratory failure. Lung transplantation (Ltx) may represent an option for CDH-related end-stage pulmonary failure. The aim of this study is to report a patient with CDH who underwent Ltx or combined heart-lung transplantation (H-Ltx). Our patient was born at 33 weeks of gestation, with a prenatally diagnosed isolated left CDH. Twenty-four hours after birth, she underwent surgical repair of a type D defect (according to the CDH Study Group staging system). Postoperative course was unexpectedly uneventful, and she was discharged home at 58 days of life. Echocardiography before discharge was unremarkable. Periodic follow-up revealed gastroesophageal reflux (GER) and initial scoliosis. At the age of 10, she was readmitted for severe PH. Lung function progressively deteriorated, and at the age of 14, she underwent H-Ltx due to end-stage respiratory failure. After discharge, she developed recurrent respiratory tract infections, severe malnutrition, and drug-induced diabetes. Scoliosis and GER progressed, requiring posterior vertebral arthrodesis and antireflux surgery, respectively. Bronchiolitis obliterans further impaired her respiratory function, and though she had a second Ltx, she died at the age of 18, 4 and 1.5 years after the first and the second Ltx, respectively. Late-onset PH is an ominous complication of CDH. From our patient and the six further cases collected from the literature, Ltx may be considered as a last-resource treatment in CDH patients with irreversible and fatal respiratory failure, although its prognosis seems unfair.
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http://dx.doi.org/10.1055/s-0038-1675377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306278PMC
January 2018
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