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. © 2016 Wiley Periodicals, Inc

In-hospital and web-based intervention to counteract vaccine hesitancy in very preterm infants’ families: a NICU experience

Background Vaccine hesitancy is a global problem, carrying significant health risks for extremely vulnerable population as that of preterm infants. Social media are emerging as significant tools for public health promotion. Our aim was to evaluate both the coverage and the timeliness of routine immunizations in a cohort of preterm infants (< 33 weeks of gestational age) at 24 months of age whose families have been subjected to in-hospital and web-based interventions to counteract vaccine hesitancy. Methods For a period of 2 years parents of preterm infants were instructed during their follow up visits by a member of the NICU team to get correct informations about vaccines from a social network page. Vaccination rates of preterm infants were assessed at 24 months of chronological age with an electronic database and compared to both general population and historical cohort. Results Coverage and timeliness of vaccinations at 24 months of age of 170 preterm infants were analyzed in December 2019. Gestational age and birth weight median (IQR) were, respectively, 31.0 (5.0) weeks and 1475.0 (843.8) g. Coverage rates were similar to those of the regional population (p > 0.05), while timeliness of administration was significantly delayed compared to the recommended schedule (p < 0.001). Age of administration was not correlated with either body weight and gestational age at birth (Spearman rank, p > 0.05). DTaP-IPV-HBV-Hib 2nd and 3rd doses, MMR and Varicella vaccines coverage data were higher compared to historical cohort (p < 0.05). Conclusion Increasing vaccine confidence through web-based interventions could have a positive impact on vaccination acceptance of parents of preterm infants, although timeliness results still delayed. There is a strong need to develop different and effective vaccination strategies to protect this very vulnerable population

Hydrolyzed protein formula for allergy prevention in preterm infants: follow-up analysis of a randomized, triple-blind, placebo-controlled study

Background: Allergic diseases are a major public health burden worldwide. Evidence suggests that early nutrition might play a key role in the future development of allergies and the use of hydrolyzed protein formulas have been proposed to prevent allergic disease, mainly in term infants with risk factors. Aim: To evaluate the preventive effect of a hydrolyzed protein formula vs. an intact protein formula on allergy development in preterm infants with or without risk factors. Methods: We performed a 3-year follow-up study of a previous triple-blind, placebo-controlled randomized trial. Evidence of atopic dermatitis, asthma and IgE-mediated food allergies were evaluated according to a validated parental questionnaire (Comprehensive Early Childhood Allergy Questionnaire). Food sensitization was also investigated by skin prick test at 3 years of chronological age. Results: Of the 30 subjects in the intact protein formula group and 30 in the extensively hydrolyzed formula group, respectively 18 and 16 completed the 3-year follow-up and entered the final analysis. No group differences in the incidence of atopic dermatitis, asthma, IgE-mediated food allergies, and food sensitization were found. Conclusion: Despite the small number of cases, extensively hydrolyzed protein formula seems to be ineffective in allergic diseases prevention in preterm neonates. Further adequately powered, randomized controlled trials evaluating hydrolyzed protein formula administration to prevent allergic diseases in preterm neonates are needed

Universal Newborn Screening for Congenital Cytomegalovirus Infection - From Infant to Maternal Infection: A Prospective Multicenter Study

Introduction: Most infants at risk for cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) are unrecognized because of the absence of a universal neonatal CMV screening. The search of CMV-DNA by molecular methods in salivary swabs was demonstrated to be a reliable approach. This study describes the results obtained by carrying out a universal screening for congenital CMV (cCMV) infection including all live-born newborns in three Italian sites, as well as the therapeutic interventions and clinical outcome of the CMV-infected neonates. Moreover, CMV maternal infection's characteristics were evaluated. Methods: To confirm or exclude cCMV infection, a CMV-DNA-positive result on a first salivary swab was followed by repeated saliva and urine samples collected within 21 days of age. Breast milk samples were also collected. The search of CMV-DNA was performed with a single automated quantitative commercial real-time PCR assay, regardless of the type of samples used. Results: A total of 3,151 newborns were enrolled; 21 (0.66%) of them were congenitally infected (median saliva viral load at screening, 6.65 [range, 5.03-7.17] log10 IU/ml). Very low/low viral load in screening saliva samples (median value, 1.87 [range, 1.14-2.59] log10 IU/ml) was associated with false-positive results (n = 54; 1.7%). CMV-DNA was detected in almost half of the breast milk samples of mother-infant pairs with a false-positive result, suggesting that contamination from breast milk may not be the only explanation in the study population. cCMV infection confirmation with the search of CMV-DNA in a urine sample proved to be the gold standard strategy, since false-positive results were observed in 4/54 (7.5%) of the repeated saliva samples. Symptomatic cCMV infection was observed in 3/21 (14.3%) infants; notably, one (4.7%) developed moderate unilateral SNHL at 5 months after birth. Finally, two symptomatic cCMV infections were associated with primary maternal infection acquired in the first trimester of gestation; one newborn with severe cCMV symptoms was born to a mother with no CMV checkups in pregnancy. Conclusion: Without universal neonatal CMV screening, some infected infants who develop late neurological sequelae may not be recognized and, consequently, they are not able to benefit early from instrumental and therapeutic interventions to limit and/or treat CMV disease

Case Report ESOPHAGEAL ATRESIA AND FOOD DISORDERS: A CASE REPORT.

Esophageal atresia is a relatively common congenital anomaly, which is often associated with other anomalies. We report a case of a newborn affected by esophageal atresia with significant post-operative and long-term complications, including feeding and swallowing disorders

Macronutrients and Micronutrients in Parenteral Nutrition for Preterm Newborns: A Narrative Review

Preterm neonates display a high risk of postnatal malnutrition, especially at very low gestational ages, because nutritional stores are less in younger preterm infants. For this reason nutrition and growth in early life play a pivotal role in the establishment of the long-term health of premature infants. Nutritional care for preterm neonates remains a challenge in clinical practice. According to the recent and latest recommendations from ESPGHAN, at birth, water intake of 70–80 mL/kg/day is suggested, progressively increasing to 150 mL/kg/day by the end of the first week of life, along with a calorie intake of 120 kcal/kg/day and a minimum protein intake of 2.5–3 g/kg/day. Regarding glucose intake, an infusion rate of 3–5 mg/kg/min is recommended, but VLBW and ELBW preterm neonates may require up to 12 mg/kg/min. In preterm infants, lipid emulsions can be started immediately after birth at a dosage of 0.5–1 g/kg/day. However, some authors have recently shown that it is not always possible to achieve optimal and recommended nutrition, due to the complexity of the daily management of premature infants, especially if extremely preterm. It would be desirable if multicenter randomized controlled trials were designed to explore the effect of early nutrition and growth on long-term health

Probiotics and Functional Gastrointestinal Disorders in Pediatric Age: A Narrative Review

Assessment and management of pain are essential components of pediatric care. Pain in pediatric age is characterized by relevant health and socio-economic consequences due to parental concern, medicalization, and long-term physical and psychological impact in children. Pathophysiological mechanisms of nociception include several pathways in which also individual perception and gut-brain axis seem to be involved. In this narrative review, we analyze the rational and the current clinical findings of probiotic use in the management of functional gastrointestinal disorders (FGID) in pediatric age, with special focus on infantile colic, irritable bowel syndrome, constipation, and gastroesophageal reflux. Some specific probiotics showed a significant reduction in crying and fussing compared to placebo in breastfed infants with colic, although their exact mechanism of action in this disorder remains poorly understood. In irritable bowel syndrome, a limited number of studies showed that specific strains of probiotics can improve abdominal pain/discomfort and bloating/gassiness, although data are still scarce. As for constipation, whilst some strains appear to reduce the number of hard stools in constipated children, the evidence is not adequate to support the use of probiotics in the management of functional constipation. Similarly, although some probiotic strains could promote gastric emptying with a potential improvement of functional symptoms related to gastroesophageal reflux, current evidence is insufficient to provide any specific recommendation for the prevention or treatment of gastroesophageal reflux. In conclusion, probiotics have been proposed as part of management of pain in functional gastrointestinal disorders in pediatric age, but mechanisms are still poorly understood and evidence to guide clinical practice is currently inadequate

Efficacy and safety of a probiotic-mixture for the treatment of infantile colic: a double-blind, randomized, placebo-controlled clinical trial

NUTRITION: Neonatal and infant nutrition N-O-001 Efficacy and safety of a probiotic-mixture for the treatment of infantile colic: a double-blind, randomized, placebo-controlled clinical trial Maria Elisabetta Baldassarre1, Manuela Capozza1, Valentina Rizzo1, Silvio Tafuri1, Antonio Di Mauro2, Nicola Laforgia1 1"Aldo Moro" University of Bari, Department of Biomedical Science and Human Oncology, Bari, Italy 2University of Bari "Aldo Moro", Neonatology and Neonatal Intensive Care Unit, Department of Biomedical Science and Human Oncology, Bari, Italy Objectives and study: Infantile colic is a causes parental distress and medical effort. Recent evidences suggest that infantile colic is low-grade systemic inflammation and Manipulation of the gut microbiota with probiotic supplementation seems to play a   therapeutic role in colic management. Aim of this study was to investigate the effectiveness and the safety of a probiotic- mixture (containing Lactobacillus plantarum DSM 24730, Streptococcus thermophilus DSM 24731, Bifidobacterium breve DSM 24732, Lactobacillus paracasei DSM 24733, Lactobacillus delbrueckii subsp. bulgaricus DSM 24734, Lactobacillus acidophilus DSM 24735, Bifidobacterium longum DSM 24736, Bifidobacterium infantis DSM 24737 and currently sold under the brand Vivomixx® in Continental Europe and Visbiome® in USA and Canada) for the treatment of infantile colic in breastfed infants, compared with placebo. Methods: A randomized, double blind, placebo-controlled trial was conducted involving exclusively breastfed infants with colic, randomly assigned to receive a probiotic-mixture or placebo for 21 days. A structured diary on gastrointestinal events in newborns, such as number of minutes of inconsolable crying per day, number of regurgitation episodes per day, number of bowel movements per day and stool consistency, was given to parents. Diaries, infants’ anthropometrics and type of adverse events were monitored weekly. The trial was registered to Clinicaltrial.gov at number: NCT01869426. Results: 59 exclusively breastfed infants completed the 3 weeks of probiotic-mixture (n.28) or placebo (n.31) treatment. Infants given probiotic-mixture showed a significant reduction in average daily episodes of fussing at the end of treatment period, compared with those receiving placebo (6,5±9,1 vs 12,7±12,7; p=0,01). Also average minutes of crying per episode on day 21 is shorter compared with infants given placebo (34,3±36,7 minutes vs 65,8±50,2 minutes; p=0,009). Total average minutes of inconsolable crying per day throughout the study were significantly shorter among colic infant in the treatment group compared with those of placebo group and reached statistical significance at the end of treatment period (214,8±338,3 minutes vs 710,4±716,0 minutes; p=0,00). No differences between groups are collected regarding infants’ anthropometric data, number of regurgitation episodes per day, number of bowel movements per day and stool consistency (p>0.05). No adverse events were reported related to the study intervention. Conclusion: Administration of a probiotic-mixture for the treatment of infantile colic is safe and significantly reduces minutes of inconsolable crying per day in exclusively breastfed infants with colic

ESOPHAGEAL ATRESIA AND FOOD DISORDERS: A CASE REPORT

Esophageal atresia is a relatively common congenital anomaly, which is often associated with other anomalies. We report a case of a newborn affected by esophageal atresia with significant post-operative and long-term complications, including feeding and swallowing disorders

Gender-related differences in neonatal age

Men and women are significantly different in their body system, and this difference has been studied in various fields of medicine. Medical research has identified a substantial group of gender-specific adult diseases, but biological differences between sexes are evident even from the beginning of pregnancy. The evaluation of gender specificities has been also extended to newborns, infants, children and adolescents. Gender-specific medicine deals with the differences between men and women both in health and diseases. Male and female fetuses react differently to the same intrauterine environment, suggesting biological variation at cellular and molecular level. Male sex is a risk factor for adverse pregnancy outcomes. There are significant sex-related differences in relation to different outcomes in preterm newborns and in the neonatal age, as well as in the incidence of congenital malformations, response to drugs during infancy, neurological and respiratory diseases. The functional and structural development of the lungs occurs earlier in females, especially in preterm newborns. In this narrative review, we describe how the sex of the fetus and the newborn can affect morbidity and mortality, both during pregnancy and after birth. Gender-related medicine can be applied to the neonatal age to evaluate disease-related sex differences. This could possibly allow for the application of preventive strategies and/or specific treatments, with a great impact on public health