Manuela Capozza

14q13 distal microdeletion encompassing NKX2-1 and PAX9: Patient report and refinement of the associated phenotype.

Chromosome 14q11‐q22 deletion syndrome (OMIM 613457) is a rare genomic disorder whose associated phenotype is heterogeneous, depending on the size, and, mostly, on the deleted region. We report the clinical and molecular characterization of a female newborn, whose phenotype was characterized by poor growth, dysmorphic facial features, subclinical hypothyroidism, and mild reduction of CD3CD8 Lymphocytes with increased CD4/CD8 ratio. By array‐CGH, we identified a 4.08 de novo interstitial deletion of the 14q13.2q21.1 region, which includes 16 OMIM genes.Our patient phenotype is compared with other published cases, for a better classification of the 14q11‐q22 deletion syndrome. We demonstrated that the 14q13.2q21.1 deletion, which encompasses NKX2‐1, but not FOXG1 gene and HPE8 region, identifies a well defined, more benign, microdeletion syndrome. This report confirms that an early identification with accurate characterization of the genomic disorders is of great relevance, enabling proper genetic counseling of the reproductive risk, as well as disease prognosis, and patient management.

New insights into childhood Vernal keratoconjunctivitis‐associated factors

The purpose of this study was to test for detectable serum levels of antibodies usually associated with immune‐related diseases in children with Vernal keratoconjunctivitis (VKC) and seek for their family history of allergies and autoimmune disorders. The association of human leukocyte antigens (HLA) with VKC was also investigated. We enrolled 181 VKC children and assessed total and specific IgE, antithyroglobulin (AbTG), antithyroidperoxidase (AbTPO), antitransglutaminase (tTG), and antinuclear antibodies (ANA) by standard procedures. Class I and II HLA typing was also carried out following standard protocols, and it was compared with that of healthy subjects. Patients were positive for AbTG (22%), AbTPO (14.6%), and ANA (15.8%), and AbTG positivity was associated with VKC severity (mean ocular scoreu2003±u2003SD positive vs. negative: 6.56u2003±u20032.1 vs. 4.82u2003±u20032.1; pu2003=u20030.03). We found that 12.2% of VKC cases had a positive family history for psoriasis, 6.4% for other cases of VKC, and 5.2% for thyroiditis, while 50.2% of them were atopic. The expression of HLA class I B37 was significantly higher in VKC patients than in controls (7.1% vs. 2.1%, pu2003=u20030.04), although not confirmed after multiple antigens testing analysis. Our study suggests a role of common components associated with immune‐based diseases in the clinical expression of VKC.

Effectiveness and Safety of a Probiotic-Mixture for the Treatment of Infantile Colic: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial with Fecal Real-Time PCR and NMR-Based Metabolomics Analysis

Introduction: To investigate the effectiveness and the safety of a probiotic-mixture (Vivomixx®, Visbiome®, DeSimone Formulation®; Danisco-DuPont, Madison, WI, USA) for the treatment of infantile colic in breastfed infants, compared with a placebo. Methods: A randomized, double-blind, placebo-controlled trial was conducted in exclusively breastfed infants with colic, randomly assigned to receive a probiotic-mixture or a placebo for 21 days. A structured diary of gastrointestinal events of the infants was given to the parents to complete. Samples of feces were also collected to evaluate microbial content and metabolome using fecal real-time polymerase chain reaction (qPCR) and Nuclear magnetic resonance (NMR)-based analysis. Study registered at ClinicalTrials.gov (NCT01869426). Results: Fifty-three exclusively-breastfed infants completed three weeks of treatment with a probiotic-mixture (n = 27) or a placebo (n = 26). Infants receiving the probiotic-mixture had less minutes of crying per day throughout the study by the end of treatment period (68.4 min/day vs. 98.7 min/day; p = 0.001). A higher rate of infants from the probiotic-mixture group responded to treatment (defined by reduction of crying times of ≥50% from baseline), on day 14, 12 vs. 5 (p = 0.04) and on day 21, 26 vs. 17 (p = 0.001). A higher quality of life, assessed by a 10-cm visual analogue scale, was reported by parents of the probiotic-mixture group on day 14, 7.1 ± 1.2 vs. 7.7 ± 0.9 (p = 0.02); and on day 21, 6.7 ± 1.6 vs. 5.9 ± 1.0 (p = 0.001). No differences between groups were found regarding anthropometric data, bowel movements, stool consistency or microbiota composition. Probiotics were found to affect the fecal molecular profile. No adverse events were reported. Conclusions: Administration of a probiotic-mixture appears safe and reduces inconsolable crying in exclusively breastfed infants.

Weaning Time in Preterm Infants: An Audit of Italian Primary Care Paediatricians

Introduction: According to the 2016 Italian National Institute of Statistics (Istat) data in Italy, about 6.7% of all newborns are born prematurely. Due to the lack of data on current complementary feeding in preterm infants in Italy, the aim of the survey was to evaluate individual attitudes of primary care paediatricians, concerning the introduction of complementary foods in preterm infants. Methods: An internet-based survey was conducted among primary care paediatricians, working in Italy, regarding (1) timing of the introduction of complementary foods to preterm newborns; (2) type of complementary foods introduced; (3) vitamin D and iron supplementations. Results: A total of 347 primary care Italian paediatricians answered the questionnaire; 44% of responders based the timing of the introduction of solid food exclusively on an infant’s age, 18% on an infant’s neurodevelopmental status and 4% on the body weight; the remaining 34% based the timing on two or more of these aspects. The type of complementary foods did not comply with an evidence-based sequence; 98% of participants promoted vitamin D supplementation and 89% promoted iron supplementation with great diversity in timing and doses. Conclusions: Due to limited evidence, there is a great heterogeneity in the attitudes of primary care paediatricians concerning the introduction of complementary foods to preterm newborns. Further research is needed to provide evidence-based guidelines regarding weaning preterm newborns.

Are pre-terms born timely and right immunized? Results of an Italian cohort study

ABSTRACT The aim of this study is to evaluate the vaccination coverage at 24 months of chronological age in a sample of preterm infants discharged by the Neonatal Intensive Care Unit (NICU) of the Bari Policlinico University General Hospital in Italy. The list of infants preterm born discharged during 2013 by the NICU was obtained by hospital database. Vaccination status of each subject at 24 months of chronological age was acquired by the Apulian Regional Vaccination Register (GIAVA). 159 preterm borns were enrolled in this study. 98.1% received the 1st dose of hexavalent vaccine and 98.7% the 1st dose of pneumococcal conjugate vaccine. The 8.8% of hexavalent vaccinations were performed during hospitalization. The percentage of immunized subjects decreased to 91.2% and 87.3% for the 2nd and 3rd dose of hexavalent vaccine and to 90.6% and 86.1% for the 2nd and 3rd dose of pneumococcal conjugate vaccine. Coverage for MMR, MEN C and Varicella vaccines were, respectively 76.4%, 86.0% and 80.9%. Pre-terms received the vaccinations later than the age recommended by public health guidelines. Age at the immunization, for all vaccines, seems to increase for lower gestational age and birth weight and for higher length of hospitalization. This study shows a high risk of vaccine delay among pre-terms born. There is a strong need to improve specific vaccination strategies for this group. Neonatologists might play a key role in informing parents about the vaccination schedule at the moment of NICU discharge and during follow-up, also preparing correct time schedule.

A Rare Case of Severe Congenital RYR1-Associated Myopathy

Congenital myopathies are a group of rare inherited diseases, defined by hypotonia and muscle weakness. We report clinical and genetic characteristics of a male preterm newborn, whose phenotype was characterized by severe hypotonia and hyporeactivity, serious respiratory distress syndrome that required mechanical ventilation, clubfoot, and other dysmorphic features. The diagnostic procedure was completed with the complete exome sequencing of the proband and of his parents and his sister, which showed new mutations in the ryanodine receptor gene (RYR1), which maps to chromosome 19q13.2 and encodes the skeletal muscle isoform of a calcium-release channel in the sarcoplasmic reticulum (RyR1). This report confirms that early diagnosis and accurate study of genomic disorders are very important, enabling proper genetic counselling of the reproductive risk, as well as disease prognosis and patient management.

Nasal high flow therapy in very low birth weight infants with mild respiratory distress syndrome: a single center experience

BackgroundPulmonary disorders and respiratory failure represent one of the most common morbidities of preterm newborns admitted to neonatal intensive care units (NICUs). The use of nasal high-flow therapy (nHFT) has been more recently introduced into the NICUs as a non-invasive respiratory (NIV) support.MethodsWe performed a retrospective study to evaluate safety and effectiveness of nHFT as primary support for infants born <u200929xa0weeks of gestation and/or VLBW presenting with mild Respiratory Distress Syndrome (RDS).The main outcome was the percentage of patients that did not need mechanical ventilation. Secondary outcomes were rate of bronchopulmonary dysplasia (BDP), air leaks, nasal injury, late onset sepsis (LOS), intraventricular hemorrhage (IVH), retinopathy (ROP), necrotizing enterocolitis (NEC), hemodynamically-significant patent ductus arteriosus (PDA) and death.ResultsSixty-four preterm newborns were enrolled. Overall, 93% of enrolled patients did not need mechanical ventilation. In a subgroup analysis, 88.5% of infants <u200929xa0weeks and 86.7% of infants ELBW (<u20091000xa0g BW) did not need mechanical ventilation.BPD was diagnosed in 26.6% of preterms enrolled (Mild 20%, Moderate 4.5%, Severe 1.5%). In subgroup analysis, BPD was diagnosed in 53.9% of newborns with GA <u200929xa0weeks, in 53.3% of ELBW newborns and in 11.1% of small for gestational age (SGA) newborns.Neither air leaks nor nasal injury were recorded as well as no exitus occurred. LOS, IVH, ROP, NEC and PDA occurred respectively in 16.1%, 0%, 7.8%, and 1.6% of newborns.ConclusionsAccording to our results, n-HFT seems to be effective as first respiratory support in preterm newborns with mild RDS. Further studies in a larger number of preterm newborns are required to confirm nHFT effectiveness in the acute phase of RDS.