Study on Nocturnal Infant Crying Evaluation (NICE) and Reflux Disease (RED).

BACKGROUND: Nocturnal infant crying is often empirically treated with acid suppressants. The aim of this study was to evaluate the prevalence and characteristics of gastroesophageal reflux (GER) in infants with unexplained persistent crying. METHODS: We enrolled all infants (0-12 months) referred for suspected GER disease who underwent esophageal impedance-pH monitoring (MII-pH) for unexplained persistent crying not improved by parental reassurance, dietary modification or alginate. Gastrointestinal malformation/surgery, neurological impairment and infections were exclusion criteria. Demographic and anthropometric parameters, GER symptoms and questionnaires (I-GERQ-R) and MII-pH data were recorded and analyzed. Normal MII-pH was defined when acid exposure was <3%, symptom index was <50% and symptom association probability was <95%. Acid exposure >5% and >10% was also considered. Statistical analysis was performed using Chi-Square and univariate and multivariable regression analysis. RESULTS: We included 50 infants (median age 3.5 months) who fulfilled the study criteria: 30 (60%) had normal MII-pH. I-GERQ-R score was abnormal in 33 (66%) infants, and 21/33 (64%) had normal MII-pH (p = 0.47). In the 26 (52%) infants with nocturnal crying, MII-pH was normal in 16 (54%) (p = 0.82). Associated regurgitation (>3 or >10 episodes/die) did not predict abnormal MII-pH (p = 0.74, p = 0.82, respectively). Univariate and multivariable regression analysis did not identify any clinical variable significantly associated with abnormal MII-pH. CONCLUSIONS: Infants with persistent unexplained and nocturnal crying should not be empirically treated with acid inhibitors.

Disrupted Seasonality of Respiratory Viruses: Retrospective Analysis of Pediatric Hospitalizations in Italy from 2019 to 2023.

This multicenter study in Italian hospitals highlights the epidemiologic disruptions in the circulation of the 5 main respiratory viruses from 2019 to 2023. Our data reveal a resurgence of respiratory syncytial virus and influenza during the 2022-2023 winter season, with an earlier peak in cases for both viruses, emphasizing the importance of timely monitoring.

Cardiac Implications of Adenotonsillar Hypertrophy and Obstructive Sleep Apnea in Pediatric Patients: A Comprehensive Systematic Review.

This review investigates the relationship between pediatric obstructive sleep apnea, often associated with adenotonsillar hypertrophy, and cardiovascular health, particularly pulmonary hypertension. We conducted a comprehensive literature search using electronic databases, including Medline Pub-Med, Scopus, and the Web of Science. The study analyzed a total of 230 articles and screened 48 articles, with 20 included in the final analysis, involving 2429 children. The PRISMA flowchart visually illustrates the selection process, and the ROBINS-E and -I tools help ensure the reliability and validity of the evidence produced by these studies. These studies explored various aspects, including the severity of obstructive sleep apnea, cardiac anomalies, cardiac stress markers, risk factors for pulmonary hypertension, and the impact of adenoidectomy and tonsillectomy on cardiac function. The research found that adenotonsillar hypertrophy and obstructive sleep apnea are significant risk factors for cardiovascular complications, especially pulmonary hypertension, in children. Adenoidectomy and tonsillectomy may provide effective treatments. Following adenoidectomy in relation to obstructive sleep apnea, there appears to be a reduction in mean pulmonary artery pressure during echocardiographic examination. However, the efficacy of these procedures can vary based on the severity of obstructive sleep apnea and individual cardiac conditions. The study also identified concerns regarding data bias. The authors emphasize the need for well-designed clinical studies, including both healthy patients with adenotonsillar hypertrophy and vulnerable children with genetic disorders, to ensure that clinical decisions are based on solid scientific evidence.

Exploring the Intricate Links between Adenotonsillar Hypertrophy, Mouth Breathing, and Craniofacial Development in Children with Sleep-Disordered Breathing: Unraveling the Vicious Cycle.

Adenotonsillar hypertrophy has been well-acknowledged as the primary instigator of sleep-disordered breathing in the pediatric population. This condition spans a spectrum, from typical age-related growth that the immune system influences to persistent pathological hypertrophy. Reduction in air spaces, metabolic changes, neurobehavioral alterations, and chronic inflammation characterizes the latter form. As the go-to treatment, adenotonsillectomy has proven effective. However, it is not a guarantee for all patients, leaving us without reliable predictors of treatment success. Evidence suggests a connection between adenotonsillar hypertrophy and specific oral breathing patterns resulting from craniofacial development. This finding implies an intricate interdependence between the two, hinting at a self-sustaining vicious cycle that persists without proper intervention. The theories regarding the relationship between craniofacial conformation and sleep-disordered breathing have given rise to intriguing perspectives. In particular, the "gracilization theory" and the "gravitational hypothesis" have provided fascinating insights into the complex interaction between craniofacial conformation and SDB. Further investigation is crucial to unraveling the underlying pathophysiological mechanisms behind this relationship. It is also vital to explore the risk factors linked to adenotonsillectomy failure, study the long-term effects of adenotonsillar hypertrophy on craniofacial growth, and devise innovative diagnostic techniques to detect upper airway compromise early. Moreover, to assess their efficacy, we must delve into novel therapeutic approaches for cases that do not respond to traditional treatment, including positional therapy and orofacial myofunctional therapy. Though complex and unpredictable, these challenges promise to enhance our understanding and treatment of adenotonsillar hypertrophy and its related complications in children. By taking on this task, we can pave the way for more effective and targeted interventions, ultimately improving affected individuals' well-being and quality of life.

Multiple Breath Washout for Early Assessment of Pulmonary Complications in Patients With Primary Antibody Deficiencies: An Observational Study in Pediatric Age.

Background: In primary antibody deficiencies (PADs), pulmonary complications are the main cause of morbidity, despite immunoglobulin substitutive therapy, antibiotic treatment of exacerbations, and respiratory physiotherapy. Current Italian recommendations for surveillance of PADs respiratory complications include an annual assessment of spirometry and execution of chest high-resolution computed tomography (HRCT) every 4 years. Objective: This study aimed to evaluate the effectiveness of the lung clearance index (LCI) as an early marker of lung damage in patients with PADs. LCI is measured by multiple breath washout (MBW), a non-invasive and highly specific test widely used in patients with cystic fibrosis (CF). Methods: Pediatric patients with PADs (n = 17, 10 male, 7 female, and age range 5-15 years) underwent baseline assessment of lung involvement with chest HRCT, spirometry, and multiple breath nitrogen washout. Among them, 13 patients were followed up to repeat HRCT after 4 years, while performing pulmonary function tests annually. Their baseline and follow-up LCI and forced expiratory volume at 1 s (FEV1) values were compared, taking HRCT as the gold standard, using logistic regression analysis. Results: Lung clearance index [odds ratio (OR) 2.3 (confidence interval (CI) 0.1-52) at baseline, OR 3.9 (CI 0.2-191) at follow-up] has a stronger discriminating power between altered and normal HRCT rather than FEV1 [OR 0.6 (CI 0.2-2) at baseline, OR 1.6 (CI 0.1-13.6) at follow-up]. Conclusion: Within the context of a limited sample size, LCI seems to be more predictive of HRCT alterations than FEV1 and more sensitive than HRCT in detecting non-uniform ventilation in the absence of bronchiectasis. A study of a larger cohort of pediatric patients followed longitudinally in adulthood is needed to challenge these findings.

Early- and Late-Respiratory Outcome in Very Low Birth Weight with or without Intrauterine Inflammation.

• IUI is a risk factor for spontaneous preterm birth and contributes to prematurity-associated mortality and morbidity.• HCA greatly affected Apgar's score and lung management of VLBWI at birth and later on with increased incidence of BPD.• HCA + FUN did not significantly impact on respiratory outcome. OBJECTIVE: Intrauterine inflammation or infection (IUI) is a risk factor for spontaneous preterm birth and contributes to prematurity-associated mortality and morbidity. IUI can include inflammation, as well as infections of varying degrees of severity and duration. Histological chorioamnionitis (HCA) remains the "gold standard" for the diagnosis but clinical, microbiological, and biochemical criteria are often used to define chorioamnionitis. The impact of intrauterine inflammation on respiratory outcome, in infants with very low birth weight, is still unclear and previous data are conflicting showing increase, decrease, or no risk of respiratory complications. STUDY DESIGN: This is a retrospective study aimed to investigate the role of IUI on neonatal respiratory outcome. Histological criteria (HCA alone and HCA + funisitis [FUN]) and "intrauterine inflammation or infection or both" "Triple I" definition were used; different management in delivery room, in the first 7 days of life (early outcome) and incidence of mild, moderate, and severe bronchopulmonary dysplasia (BPD; late outcome) were considered. RESULTS: A total of 162 infants with very low birth weight (VLBW) with placenta histology were enrolled. Suspected TRIPLE or fever alone was present in 7.4%, and confirmed TRIPLE or HCA in 29.6% of cases (HCA alone 19.1% vs. HCA + FUN 10.5%). Preterm premature rupture of membrane (p-PROM) was strongly associated with HCA (66.6% in HCA group) and HCA was present in 80% neonates born between 22 and 24 weeks of gestational age (GA). HCA group (GA, 26 weeks; birth weight [BW], 880 g) showed lower Apgar's score, higher intubation rate, and need of ventilation in delivery room, surfactant, duration of noninvasive ventilation (NIV), severe patent ductus arteriosus (PDA), and incidence of BPD compared with no-HCA (GA, 30 weeks; BW, 1,210 g). Length of hospital stay and mortality were higher in HCA group (p = 0.01) and an increasing trend was present for HCA + FUN compared with HCA alone. CONCLUSION: HCA greatly affected Apgar's score and lung management of VLBW infants (VLBWI) at birth and later on with increased incidence of BPD, thus impacting length of stay and quality of life, while HCA + FUN did not significantly impact on respiratory outcome. Further studies are needed to clarify the role of HCA and FUN in VLBW neonates.

Williams-Beuren Syndrome and celiac disease: A real association?

Celiac disease (CD) screening in patients with Williams-Beuren Syndrome (WBS) is suggested, although data described in literature are discordant regarding CD prevalence in WBS. We retrospectively collected data from 101 WBS Italian patients [mean age: 13.5 years], to clarify the CD prevalence in a large cohort. All patients underwent a CD biochemical screening: IgA and anti-transglutaminase reflex antibodies (tTGA). CD-specific HLA typing was available for 42 patients. Small intestinal biopsy was performed in patients according to ESPGHAN guidelines. In 7 WBS patients an overt celiac disease was diagnosed. In 3 patients CD was confirmed by symptoms, HLA-DQ heterodimers and CD specific antibodies title, whereas in 4 patients, it was confirmed by a small intestinal biopsy. CD prevalence in our cohort is 6.9% (7/101). In 42/101 patients the CD-specific HLA typing was available, detecting 29/42 (69%) patients genetically predisposed to CD. The CD prevalence and CD-specific HLA prevalence are both higher than in the general population (p < 0.001; p < 0.001). Our cohort is the most numerous described confirming that the CD risk in WBS patients is significantly greater than in general population. Moreover, our HLA typing results, as well as scientific literature, suggest that the higher CD prevalence in WBS patients might not be intrinsically related to the genetic disease itself but with the higher HLA prevalence. However, HLA typing should be performed in bigger WBS cohorts to confirm this hypothesis. Our data confirms that HLA typing is mandatory in WBS patients and that CD screening should be performed only if genetically predisposed.

Laryngeal signs and pH-multichannel intraluminal impedance in infants and children: The missing ring: LPR and MII-pH in children.

OBJECTIVE: to investigate the reliability of laryngeal reflux finding score (RFS) and symptom index (RSI) in assessing gastroesophageal reflux (GER) in children and infants. METHODS: patients with laryngeal or respiratory symptoms, who underwent laryngoscopy and esophageal pH-impedance (MII-pH) were recruited. RSI and RFS were correlated to MII-pH results. A RSI>13, RFS>7, acid exposure index>7%, total reflux episodes>100/24 h in infants or>70/24 h in children, or a positive symptom index or association probability, were considered pathological. Analysis considering age (12 months) was performed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the laryngeal scores were calculated. RESULTS: 197 children (median 53 months, 61 infants) were enrolled. MII-pH was pathological in 5/10 patients with RFS>7, and in 17/31 with RSI>13. RFS>7 had 3.9% sensitivity, 93% specificity, a PPV of 50 and a NPV of 34 in predicting GER disease. RFS was inversely associated to weakly acidic and proximal GER. RSI>13 had 13% sensitivity, 83% specificity, and a PPV and NPV similar to RFS. RSI was significantly associated with the number of acid reflux episodes, and, in infants, with bolus exposure index. CONCLUSIONS: RSI and RFS aren't accurate in predicting GER in infants and children. Acid reflux relates to laryngeal symptoms, but neither acid, nor proximal and weakly acidic GER relate to laryngeal alterations.

Age and Upper Airway Obstruction: A Challenge to the Clinical Approach in Pediatric Patients.

Upper airway abnormalities increase the risk of pediatric morbidity in infants. A multidisciplinary approach to obstructive sleep apnea syndrome (OSAS) poses challenges to clinical practice. The incidence and causes of OSA are poorly studied in children under 2 years of age. To fill this gap, we performed this retrospective observational study to determine the causes of obstructive sleep apnea (OSA) in children admitted to our hospital between January 2016 and February 2018, after a brief unexplained event (BRUE) or for OSA. We reviewed the medical charts of 82 patients (39 males; BRUE n = 48; OSAS n = 34) and divided them into two age groups: < 1 year old (1-12 months; n = 59) and >1 year old (>12-24 months; n = 23). Assessment included nap polysomnography, multichannel intraluminal impedance-pH, and nasopharyngoscopy. Sleep disordered breathing was comparable between the two groups. Omega-shaped epiglottis, laryngomalacia, and nasal septum deviation were more frequent in the younger group, and nasal congestion in older group. Tonsillar and adenoidal hypertrophy was more frequent in the older group, while laryngomalacia and gastroesophageal reflux was more frequent in the younger group. Tonsil and adenoid size were associated with grade of apnea-hypopnea index severity in the older group, and laryngomalacia and gastroesophageal reflux in the younger group. The main causes of respiratory sleep disorders differ in children before or after age 1 year. Our findings have potential clinical utility for assessing the pathophysiology of obstructive sleep disordered breathing in patients less than 2 years old.

Risk and Protective Factors for Gastrointestinal Symptoms associated with Antibiotic Treatment in Children: A Population Study.

PURPOSE: Gastrointestinal symptoms are often related to antibiotic treatment. Their incidence, risk and protective conditions in children are not well defined and represent the aims of this study. METHODS: We prospectively enrolled inpatient children submitted to antibiotic treatment. Indication, type, dose and duration of treatment, probiotic supplementation and gastrointestinal symptoms were recorded at recruitment, after two and four weeks. Antibiotic-associated diarrhea (AAD) was defined as the presence of at least 3 loose/liquid stools within 14 days from antibiotic onset. RESULTS: AAD occurred in 59/289 (20.4%) of patients, with increased risk in children younger than 3 years (relative risk [RR]=4.25), in lower respiratory (RR=2.11) and urinary infections (RR=3.67), intravenous administration (RR=1.81) and previous AAD episodes (RR=1.87). Abdominal pain occurred in 27/289 (9.3%), particularly in children >6 years (RR=4.15), with previous abdominal pain (RR=7.2) or constipation (RR=4.06). Constipation was recorded in 23/289 (8.0%), with increased risk in children having surgery (RR=2.56) or previous constipation (RR=7.38). Probiotic supplementation significantly reduced AAD (RR=0.30) and abdominal pain (RR=0.36). Lactobacillus rhamnosus GG (LGG) and L. reuteri significantly reduced AAD (RR=0.37 and 0.35) and abdominal pain (RR=0.37 and 0.24). CONCLUSION: AAD occurred in 20.4% of children, with increased risk at younger age, lower respiratory and urinary tract infections, intravenous treatment and previous AAD. LGG and L. reuteri reduced both AAD and associated abdominal pain.

Prenatal and accurate perinatal diagnosis of type 2 H or ductular duplicate gallbladder.

BACKGROUND: Double gallbladder is a rare biliary anomaly. Perinatal diagnosis of the disorder has been reported in only 6 cases, and in 5 of them the diagnosis was based on ultrasound imaging only. However, the ultrasound technique alone does not provide a sufficiently precise description of cystic ducts and biliary anatomy, an information that is crucial for a correct classification and for a possible future surgery. CASE PRESENTATION: At 21 weeks of gestational age of an uneventful pregnancy in a 38 year old primipara mother, a routine ultrasound screening detected a biliary anomaly in the fetus suggestive of a double gallbladder. A neonatal abdominal ultrasonography performed on postnatal day 2 confirmed the diagnosis. On day 12 the newborn underwent a Magnetic Resonance Cholangiopancreatography (MRCP) that clearly characterized the anatomy of the anomaly: both gallbladders had their own cystic duct and both had a separate insertion in the main biliary duct. CONCLUSIONS: We report a case of early prenatal suspected duplicate gallbladder that was confirmed by a neonatal precise diagnosis of a Type 2, H or ductular duplicate gallbladder, using for the first time 3D images of Magnetic resonance cholangiopancreatography in a newborn. An accurate anatomical diagnosis is mandatory in patients undergoing a possible future cholecystectomy, to avoid surgical complications or reoperations. Therefore, in case of a perinatal suspicion of a double gallbladder, neonates should undergo a Magnetic resonance cholangiopancreatography. A review of the Literature about this variant is included.

Effects of Red Blood Cell Transfusions on the Risk of Developing Complications or Death: An Observational Study of a Cohort of Very Low Birth Weight Infants.

Background The aim of this study was to evaluate the association between red blood cell (RBC) transfusions on the risk of death, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. Study Design and Methods This is an observational study. Data were entered prospectively into the study database at the time of the first transfusion. Clinical characteristics, adverse events, and outcomes of the patients transfused in the first 28 days of life were compared with the population of VLBW infants not transfused during the same period. The association among birth weight, gestational age, comorbidities, and the number of transfusions was estimated with a Poisson regression model. The association between the composite outcome and the occurrence of death, ROP, or BPD separately considered and a set of covariates was estimated with a logistic regression model. Results We enrolled 641 VLBW infants, 42% of whom were transfused. Transfusions were associated with the risk of developing the composite outcome, independently from other conditions; this risk correlated with several transfusions ≥ 3 (odds ratio: 5.88, 95% confidence interval: 2.74-12.6). ROP and BPD were associated with several transfusions ≥ 3. Conclusion We observed an association between RBC transfusions and the composite risk of death or ROP, BPD, and NEC.

Does parental involvement affect the development of feeding skills in preterm infants? A prospective study.

BACKGROUND: Feeding difficulties frequently occur in preterm infants, thus contributing to delayed growth and hospital discharge. AIMS: To evaluate the effect of Kangaroo mother care implementation and parental involvement in infants' feeding on the timing of achievement of full oral feeding in preterm infants. STUDY DESIGN: Prospective, observational, single-centre study. SUBJECTS: A total of 81 infants born at a gestational age ≤32weeks, consecutively admitted to a tertiary neonatal unit between June 2014 and May 2015. OUTCOME MEASURES: The timing of the achievement of full oral feeding of preterm infants. RESULTS: Full oral feeding was achieved at a mean postmenstrual age of 35.5±2.1weeks. A multiple linear regression analysis showed that a low birth weight, the occurrence of bronchopulmonary dysplasia, and the need for gastrointestinal surgical procedures were associated with a higher postmenstrual age at achievement of full oral feedings. By contrast, the earlier that parents fed their infants and the earlier that Kangaroo mother care was started, the lower the postmenstrual age at the achievement of full oral feeding. CONCLUSIONS: These findings indicate that an early start of Kangaroo mother care and early parental involvement in infants' feeding positively affect the achievement of independent oral feeding.

Fertility rates, course of pregnancy and perinatal outcomes after laparoscopic ureterolysis for deep endometriosis: A long-term follow-up study.

We evaluated fertility rates, pregnancy course and maternal/neonatal outcomes following laparoscopic ureterolysis for deep endometriosis. Data about women who underwent laparoscopic excision of ureteral endometriosis were analysed. After exclusion of women who underwent hysterectomy/bilateral adnexectomy at initial surgery, and those lost-to-follow-up or with follow-up <1 year, a total of 61 patients were included. Of them, 36 (59%) wished to conceive after surgery. Twenty women became pregnant: nine (45%) of them after assisted reproductive technologies. Twenty-six pregnancies were observed with four (15.6%) miscarriages. Median gestational week at delivery was 38 weeks + 2 days (range, 33 + 1-41 + 6), with three (13.6%) and two (9%) deliveries before 37 and 34 weeks, respectively. Nine caesarean sections were performed (40.9%). Fertility rates after laparoscopic ureterolysis are comparable to those of other women operated for other forms of deep endometriosis. Apart from a higher risk of caesarean and preterm birth, the course of pregnancy and peripartum outcomes appear encouraging.

Sustained lung inflation at birth for preterm infants: a randomized clinical trial.

BACKGROUND: Studies suggest that giving newly born preterm infants sustained lung inflation (SLI) may decrease their need for mechanical ventilation (MV) and improve their respiratory outcomes. METHODS: We randomly assigned infants born at 25 weeks 0 days to 28 weeks 6 days of gestation to receive SLI (25 cm H2O for 15 seconds) followed by nasal continuous positive airway pressure (nCPAP) or nCPAP alone in the delivery room. SLI and nCPAP were delivered by using a neonatal mask and a T-piece ventilator. The primary end point was the need for MV in the first 72 hours of life. The secondary end points included the need for respiratory supports and survival without bronchopulmonary dysplasia (BPD). RESULTS: A total of 148 infants were enrolled in the SLI group and 143 in the control group. Significantly fewer infants were ventilated in the first 72 hours of life in the SLI group (79 of 148 [53%]) than in the control group (93 of 143 [65%]); unadjusted odds ratio: 0.62 [95% confidence interval: 0.38-0.99]; P = .04). The need for respiratory support and survival without BPD did not differ between the groups. Pneumothorax occurred in 1% (n = 2) of infants in the control group compared with 6% (n = 9) in the SLI group, with an unadjusted odds ratio of 4.57 (95% confidence interval: 0.97-21.50; P = .06). CONCLUSIONS: SLI followed by nCPAP in the delivery room decreased the need for MV in the first 72 hours of life in preterm infants at high risk of respiratory distress syndrome compared with nCPAP alone but did not decrease the need for respiratory support and the occurrence of BPD.

Sustained lung inflation in the delivery room in preterm infants at high risk of respiratory distress syndrome (SLI STUDY): study protocol for a randomized controlled trial.

BACKGROUND: Some studies have suggested that the early sustained lung inflation (SLI) procedure is effective in decreasing the need for mechanical ventilation (MV) and improving respiratory outcome in preterm infants. We planned the present randomized controlled trial to confirm or refute these findings. METHODS/DESIGN: In this study, 276 infants born at 25(+0) to 28(+6) weeks' gestation at high risk of respiratory distress syndrome (RDS) will be randomized to receive the SLI maneuver (25 cmH2O for 15 seconds) followed by nasal continuous positive airway pressure (NCPAP) or NCPAP alone in the delivery room. SLI and NCPAP will be delivered using a neonatal mask and a T-piece ventilator.The primary endpoint is the need for MV in the first 72 hours of life. The secondary endpoints include the need and duration of respiratory support (NCPAP, MV and surfactant), and the occurrence of bronchopulmonary dysplasia (BPD). TRIAL REGISTRATION NUMBER: NCT01440868.