Classic Galactosemia: Clinical and Computational Characterization of a Novel GALT Missense Variant (p.A303D) and a Literature Review.

Classic galactosemia is an autosomal recessive inherited liver disorder of carbohydrate metabolism caused by deficient activity of galactose-1-phosphate uridylyltransferase (GALT). While a galactose-restricted diet is lifesaving, most patients still develop long-term complications. In this study, we report on a two-week-old female patient who is a compound heterozygote for a known pathogenic variant (p.K285N) and a novel missense variant (p.A303D) in the GALT gene. Segregation analysis showed that the patient inherited the p.K285N pathogenic variant from her father and the p.A303D variant from her mother. A bioinformatics analysis to predict the impact of the p.A303D missense variant on the structure and stability of the GALT protein revealed that it may be pathogenic. Based on this finding, we performed a literature review of all GALT missense variants identified in homozygous and compound heterozygous galactosemia patients carrying the p.K285N pathogenic variant to explore their molecular effects on the clinical phenotype of the disease. Our analysis revealed that these missense variants are responsible for a wide range of molecular defects. This study expands the clinical and mutational spectrum in classic galactosemia and reinforces the importance of understanding the molecular consequences of genetic variants to incorporate genetic analysis into clinical care.

Survival of infants treated with CKRT: comparing adapted adult platforms with the Carpediem™.

BACKGROUND: The most severely ill neonates and infants with AKI who need kidney replacement therapy have had to rely upon peritoneal dialysis, or adaptations of veno-venous continuous kidney replacement therapy (CKRT) devices for adults. Data from the Prospective Pediatric CRRT (ppCRRT) registry observed children < 10 kg had a lower survival rate than children > 10 kg (44% vs. 64%, p < 0.001). A CKRT device designed specifically for small children could improve outcomes. The Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM™) is specifically dedicated to providing CKRT for newborns and small infants. METHODS: We performed a retrospective cohort analysis comparing patient severity of illness and outcomes between the ppCRRT and CARPEDIEM registries, involving 6 Italian pediatric intensive care units. Thirty-eight subjects from the CARPEDIEM registry and 84 subjects from the ppCRRT registry < 10 kg were screened for comparison. We compared patient outcomes with a weight-matched cohort (< 5 kg) of 34 patients from the CARPEDIEM registry and 48 patients from the ppCRRT registry. RESULTS: The ppCRRT subjects had higher rates of vasoactive medication at CKRT initiation. Survival to CKRT termination was higher for CARPEDIEM subjects (33/34 vs. 21/48, p < 0.0001). Multivariable logistic regression showed that CARPEDIEM registry cohort was the only variable to retain an association with survival to CKRT discontinuation. CONCLUSIONS: We suggest children receiving CKRT using CARPEDIEM have excellent survival. Our data should be interpreted with caution given the retrospective comparison across two eras more than a decade apart.

Maternal Psychological Factors and Onset of Functional Gastrointestinal Disorders in Offspring: A Prospective Study.

BACKGROUND/OBJECTIVES: Functional gastrointestinal disorders (FGIDs) are a heterogeneous group of conditions of unclear etiology. The biopsychosocial model approach to FGIDs posits that early-life stressors may trigger a cascade of complex interactions between genetic predisposition and risk factors eventually leading to the occurrence of FGIDs. The relationship between the psychological disposition of the mother and FGIDs occurrence is poorly understood. We conducted a study to investigate if parental psychological factors may contribute to the onset of FGIDs in offspring. METHODS: We performed a prospective cohort study of parent-infant pairs who completed a battery of self-reported psychological questionnaires and a validated Rome III questionnaire for the diagnosis of infant and toddler FGIDs. The Edinburgh Postpartum Depression Scale (EPDS) was used to examine postpartum depression (PPD) symptoms; the Maternity Blues Questionnaire (MBQ) was applied to measure maternity blues severity; the Symptoms Checklist-Revised (SCL90-R) was used to assess the presence of relevant psychiatric symptoms; adult attachment style in mothers was assessed in a continuous way through the five dimensions of the Attachment Style Questionnaire (ASQ). RESULTS: Out of the 360 eligible mothers, 200 were enrolled, 113 completed the 3-month follow-up and were included in the final analysis. PPD symptoms prevalence was 20.4%, 20%, 13.2%, and 13.1% respectively at 3 days, 1 week, 1 month, and 3 months after delivery. 40.4% of mothers suffered from severe blues according to the MBQ. Relevant psychiatric symptoms (SCL90-R) were present in 7.8% and 10.9% of mothers, respectively at 1 week and 3 months after delivery. 48.7% of mothers showed a secure attachment pattern measured through the RQ. At 1-month follow-up, infant regurgitation was diagnosed in 26 (23%) of infants, infantile colic in 31 (27.4%), dyschezia in 17 (15%), and functional constipation in 9 (8%). At 3-month follow-up, FGIDs prevalence was respectively 16 (19.3%), 11 (13.3%), 4 (4.8%), and 11 (13.3%). A significant positive association between PPD symptoms starting 3 days after delivery and the presence of infantile colic on setting 1 month after birth was found (P = 0.028), as well as between PPD symptoms occurrence 7 days after delivery and infantile regurgitation beginning 1 month after birth (P = 0.042). A higher prevalence of infantile colic was found in the offspring of mothers suffering from PPD symptoms from 3 days after delivery (54.5 vs 19.8; P = 0.001). No significant association was found between FGIDs and psychiatric symptoms and maternity blues at any timepoint. On the other hand, mothers of infants with regurgitation with an onset 1 month after birth have higher insecurity score in avoidant and fearful ASQ-related attachment dimensions (respectively, P = 0.03, P = 0.042, P = 0.03). CONCLUSIONS: Maternal psychological factors might contribute to the onset of infant FGIDs in offspring. Early screening of postpartum depression symptoms and early implementation of psychological interventions within the postpartum period might promote the health of the mother-infant dyad.

Correction to: Case-management protocol for bloody diarrhea as a model to reduce the clinical impact of Shiga toxin-producing Escherichia coli infections. Experience from Southern Italy.

In the originally published article, the name of the 8th author Michele Quarto was inadvertently omitted during typesetting. Author's name is now correctly captured above. Also, the collaborators of the institutional group "Bloody Diarrhea Apulia Working Group" are also given here.

Case-management protocol for bloody diarrhea as a model to reduce the clinical impact of Shiga toxin-producing Escherichia coli infections. Experience from Southern Italy.

To describe an operating protocol for bloody diarrhea (BD) in a pediatric population as a rapid response to a public health threat represented by an excess of pediatric HUS cases in the Apulia region (Southern Italy) starting from 2013. The protocol was set up with the goal of correct clinical management of Shiga toxin-producing Escherichia coli (STEC) infections, reductions in subsequent cases of hemolytic uremic syndrome (HUS), and improved short- and long-term disease outcomes. The protocol consisted of rapid hospitalization of children with bloody diarrhea (BD), hematochemical laboratory tests every 12-24 hours, and prompt laboratory diagnosis of STEC. No antibiotics were recommended until diagnosis. Children positive for STEC infections underwent early vigorous volume expansion. In June-December 2018, 438 children with BD were hospitalized, of which 53 (12.1%) had a STEC infection. The most common serogroups were O26 (36.1%), O111 (23.0%), and O157 (14.8%). Thirty-one samples carried the stx2 gene. Four cases evolved into HUS (7.5%), all with favorable outcome despite neurological involvement in two cases. Prompt and accurate laboratory diagnosis of STEC infections is of the utmost importance in patients with BD for correct clinical management. The strict adherence to the protocol could reduce the progression rate of STEC infections to HUS and prevents complications. Enhanced BD surveillance may help reduce cases of pediatric HUS in Southern Italy.

Drug exposure for PDA closure in France: a prospective, cohort-based, analysis.

PURPOSE: To describe the exposure to drugs used for the treatment of patent ductus arteriosus (PDA) in a large cohort of preterm infants born before 32 weeks of gestation. METHODS: A prospective observational cohort analysis was conducted during 2 years in 28 French level 3 NICU using the same computerized order-entry system. The main outcome was "a medically treated PDA," defined as exposure to ibuprofen, indomethacin, or paracetamol prescribed with the indication of PDA closure. Secondary outcomes were as follows: time of the first treatment administration; total exposure to furosemide during hospitalization; and rate of PDA refractory to pharmacological closure. RESULTS: The study cohort consisted of 2614 infants. Among them, 474 (18.1%) received a medical treatment for PDA, with a mean postnatal age at treatment of 4.3 ± 6.6 days. The drug used as a first-line treatment was ibuprofen in 89.5% and paracetamol in 10.5%. One hundred and ninety-five infants (7.4%) had a PDA refractory to pharmacological closure. At the multivariate analysis, factors associated with PDA refractory to pharmacological closure (OR; 95% CI) were as follows: gestational age (GA) (0.81; 0.72-0.90), paracetamol as the first-line treatment (0.32; 0.15-0.68), and pharmacological treatment before 48 h of life (0.63; 0.43-0.94). 24.6% of the study cohort was exposed to furosemide (cumulative dose 6.5 ± 12.6 mg/kg). Variables significantly associated with higher cumulative doses of furosemide were lower GA and ibuprofen treatment (both p < 0.0001). CONCLUSION: Drug utilization patterns in infants with PDA vary among centers. Pharmacoepidemiology studies can provide new information on factors associated with PDA refractory to medical treatment.

Continuous kidney replacement therapy in critically ill neonates and infants: a retrospective analysis of clinical results with a dedicated device.

BACKGROUND: Providing extracorporeal renal support to neonates and infants involves a number of technical and clinical issues, possibly discouraging early utilization. This report aims to describe a multicenter experience of continuous kidney replacement therapy (CKRT) delivery to small infants using a device specifically designed for this age group. METHODS: A retrospective cohort analysis of all patients treated with the Carpediem™ machine (Bellco-Medtronic, Mirandola, Italy) in 6 centers between June 2013 and December 2016. RESULTS: Twenty-six neonates and small infants received 165 CKRT sessions in convective modality. Median age at neonatal intensive care unit admission 1 day (IQR 1-11), median body weight 2.9 kg (IQR 2.2-3.6). Median circuit duration 14 h (IQR 10-22), with delivered/prescribed time ratio of 84%. CKRT was conducted using 4 Fr (27%), 5 Fr (35%), 6.5 Fr (11%), and 7 Fr (3%) vascular access, and with umbilical and peripheral accesses (11% each) allowing overall median blood flow of 4.5 ml/kg/min (IQR 3.4-6) and median effluent flow rate 35 ml/kg/h (IQR 28-42). Circuits were primed with normal saline in 58% of treatments, colloids in 31%, and packed red blood cells in 11%. No serious adverse events directly related to machine application were reported by any center. Twenty-five (96%) patients survived their CKRT course and 13 patients (50%) survived to ICU discharge. CONCLUSIONS: CKRT in neonates was easy to initiate and conduct when performed with small central vascular accesses coupled with this device. A dedicated technology for infant CKRT delivery enables patients to be safely treated avoiding technical complications. Graphical abstract.

Pigtail catheters versus traditional chest drains for pneumothorax treatment in two NICUs.

Pneumothorax in newborns can be life-threatening. The traditional treatment of pneumothorax is chest drain placement. Recently, modified pigtail catheter has been proposed as a less traumatic approach despite limited experience in infants. To compare the effectiveness and safety of pigtail catheters versus traditional straight chest drains in term and preterm infants with pneumothorax, in two tertiary neonatal units: Policlinico Hospital in Bari, IT and John Radcliffe Hospital in Oxford, UK. We retrospectively reviewed medical records of 47 newborns with pneumothorax admitted to the two units between October 2009 and June 2017, and treated with either pigtail catheters or straight chest drains. Three newborns (6.7%) were excluded from the study because they were treated with both types of drains. The remaining 44 neonates were included in the analysis. Overall, 56.8% (n = 25/44) of pneumothoraces were drained with pigtail catheters and 43.2% (n = 19/44) with straight drains. No differences in gestational age and birth weight were found. The success rate, defined as complete radiological resolution of the pneumothorax after drainage, was significantly higher in the pigtail group (96.0% versus 73.7%; p < 0.05). Days of drainage, length of hospital stay and duration of respiratory support were not significantly different. Subcutaneous emphysema and drain dislodgement/malfunction occurred only in the straight drain group (0.0% versus 11.1%; p = 0.181). No significant differences in mortality between the two groups were found (28.0% pigtail group versus 26.3% straight drain group; p > 0.05).Conclusion: Pigtail catheters are a safe and effective alternative to traditional chest drains for infants with pneumothorax. What is Known:• Air leaks in newborns can represent an emergency, especially among preterms;• The first treatment in a life-threatening pneumothorax is thoracentesis with needle aspiration or placement of a chest drain.What is New:• Pigtail catheter have been described as an alternative to traditional chest drains;• Pigtail catheters are a safe and effective alternative to traditional chest drains for infants with pneumothorax.

Systematic review found that using thin catheters to deliver surfactant to preterm neonates was associated with reduced bronchopulmonary dysplasia and mechanical ventilation.

AIM: Surfactant delivery is a cornerstone for managing respiratory distress in preterm neonates, but data on the best surfactant delivery methods have been conflicting. METHODS: A systematic literature review using the PubMed, Embase, Cochrane Library and Web of Science databases identified papers published up to November 5, 2019. Additional studies were identified from trial registries, conference proceedings and the reference lists of the selected papers. RESULTS: We identified 15 studies covering 4926 preterm infants. The randomised controlled trials (RCTs) and observational studies both showed significant reductions in early intubation rates with use of thin catheters. The relative risk (RR) was 0.63 and the 95% confidence interval (95% CI) was 0.55-0.72 (P < .01), with an odds ratio (OR) of 0.40 and 95% CI of 0.35-0.45 (P < .0001). The collective results from the RCTs revealed a significant decrease in bronchopulmonary dysplasia (BPD) rates in the thin catheter group (RR, 0.47; 95% CI 0.33-0.66; P < .01). These findings were consistent with the observational studies (OR 0.47; 95% CI 0.43-0.52; P < .01). CONCLUSION: Using thin catheters to deliver surfactant in comparison with intubate-surfactant-extubate (INSURE) to newborn preterm infants with respiratory distress was associated with a reduced incidence of BPD and less need for mechanical ventilation.

The role of very low birth weight and prematurity on cardiovascular disease risk and on kidney development in children: a pilot study.

BACKGROUND: Cardiovascular and renal disease are nowadays among the leading cause of morbidity and mortality in Western Countries. Low birth weight has been recently considered a key factor in determining cardiovascular disease and long-term renal disease in adulthood. METHODS: In our study we analyzed, through echocardiography, eco color Doppler of carotid arteries, ultrasound of abdominal aorta and kidneys, morphological characteristics of cardiovascular and renal system, in a group of children born preterm with very low birth weight, (birth weight<1500 grams) and in a group of children, age and sex matched, born at term with weight appropriate for gestational age. Fifteen children born very low birth weight preterm (cases), aged from 3 to 5 years, and 15, age and sex matched children, born appropriate for gestational age at term (controls) were enrolled in the study. RESULTS: The two groups were homogeneous for interventricular septum diameter, left ventricular end-systolic diameter, left atrial diameter, and ejection fraction. Left ventricular end diastolic diameter was higher in case compared to controls (P=0.04), while aortic diameter root smaller (P=0.005). E and A waves peak velocities and E/A ratio resulted lower in cases compared to controls (P=0.02, P<0.001and P<0.001, respectively). Tei index, S, e' and a' waves velocities were similar in the two groups, while E/e' ratio was higher in cases (P=0.046). Intima-media thickness and antero-posterior diameter of abdominal aorta values did not differ in cases versus controls. Longitudinal diameters of both kidneys were reduced in cases compared to controls (P<0.05). CONCLUSIONS: Although limited by the small sample size, our study highlighted an increased size of the left ventricle and altered left ventricular diastolic function in children born very low birth weight preterm, but no long-term consequences on systolic performance and vascular structure have been found. The finding of smaller kidneys in ex-preterm very low birth weight children could explain their higher susceptibility to develop renal disease in adulthood.

Neonatal Antibiotics and Prematurity Are Associated with an Increased Risk of Functional Gastrointestinal Disorders in the First Year of Life.

OBJECTIVE: To assess the prevalence of functional gastrointestinal disorders (FGIDs) in the first year of life and the influence of different neonatal factors on development of FGIDs. STUDY DESIGN: A prospective cohort multicenter study including neonates, consecutively enrolled at birth, and followed up until 1 year. Gestational age, neonatal antibiotic administration, duration of hospitalization, mode of delivery, birth weight, and feeding pattern were recorded. FGIDs were classified according to Rome III criteria and assessed at 1, 3, 6, and 12 months of life. RESULTS: Among 1152 newborns enrolled, 934 (81.1%) completed the study, 302 (32%) were newborns born preterm, 320 (34%) had neonatal antibiotics, and 718 (76.9%) had at least 1 FGID according to Rome III criteria (443 [47.4%] infantile colic, 374 [40.0%] regurgitation, 297 [31.8%] infant dyschezia, 248 [26.6%] functional constipation, and 34 [3.6%] functional diarrhea) throughout the first year of life. The proportion of infants born preterm presenting with FGIDs (86%) was significantly greater compared with infants born full term (72.5%) (χ2 = 21.3, P = .0001). On multivariate analysis, prematurity and neonatal use of antibiotics was significantly associated with at least 1 FGID. CONCLUSIONS: We found a high rate FGIDs in infants, likely related to the population recruited, the long observation period, the diagnosis based on Rome III criteria, and parental reports. Preterm delivery and neonatal use of antibiotics in the first months of life are associated with an increased incidence of FGIDs, particularly infantile colic and regurgitation. In our population, cesarean delivery and feeding pattern at 1 month of life emerged as additional risk factors for infant dyschezia and functional diarrhea. Other neonatal factors associated with FGIDs need to be further explored.

Correction to: Case report: acute clinical presentation and neonatal management of primary hyperparathyroidism due to a novel CaSR mutation.

In the published article [1], an error has been noticed in the author group section.

Lung Ultrasound: A New Tool in the Management of Congenital Lung Malformation.

OBJECTIVE: This study was aimed to evaluate effectiveness of lung ultrasound (LUS) in the management of congenital pulmonary airway malformation and pulmonary sequestration in NICUs. STUDY DESIGN: This is a nonconsecutive case series of neonates admitted to the academic NICU of Policlinico of Bari, Italy, from 2010 to 2018, for suspected lung malformations and examined by LUS. RESULTS: Seven neonates were admitted for suspected pulmonary malformations, four neonates were diagnosed with pulmonary sequestration and three with congenital pulmonary airway malformation either type I (two cases) or type II (one case) according to Adzick classification. Prenatal scans had described lung malformations in six patients. Two underwent surgical intervention during the 1st month of life. All were successfully discharged home and their follow-up has been uneventful thereafter. In all the seven neonates, LUS easily detected the lesion showing a significantly high correspondence with computed tomography (CT) scan findings. CONCLUSION: We described the first case series of neonates affected by complex pulmonary malformations, assessed by LUS. In our experience, LUS was safe and effective for the diagnosis with high degree of consistency with CT scan findings. We suggest that LUS might be an important diagnostic method for lung malformations in newborns and a useful technique for their follow-up and late management, avoiding multiple exposures to radiations.

Is Lactoferrin More Effective in Reducing Late-Onset Sepsis in Preterm Neonates Fed Formula Than in Those Receiving Mother's Own Milk? Secondary Analyses of Two Multicenter Randomized Controlled Trials.

BACKGROUND: Lactoferrin is the major antimicrobial protein in human milk. In our randomized controlled trial (RCT) of bovine lactoferrin (BLF) supplementation in preterm neonates, BLF reduced late-onset sepsis (LOS). Mother's own milk (MM) contains higher concentrations of lactoferrin than donor milk or formula, but whether BLF is more effective in infants who receive formula or donor milk is uncertain. AIM: To evaluate the incidence of LOS in preterm infants fed MM and in those fed formula and/or donor milk. STUDY DESIGN: This is a (A) post hoc subgroup analysis, in our RCT of BLF, of its effects in preterm infants fed MM, with or without formula, versus those fed formula and/or donor milk (no-MM) and (B) post hoc meta-analysis, in our RCT of BLF and in the ELFIN (Enteral Lactoferrin in Neonates) RCT, of the effect of BLF in subgroups not exclusively fed MM. RESULTS: (A) Of 472 infants in our RCT, 168 were randomized to placebo and 304 were randomized to BLF. Among MM infants, LOS occurred in 22/133 (16.5%) infants randomized to placebo and in 14/250 (5.6%) randomized to BLF (relative risk or risk ratio (RR): 0.34; relative risk reduction (RRR): 0.66; 95% confidence interval (95% CI) for RR: 0.18-0.64; p < 0.0008). Among no-MM infants, LOS occurred in 7/35 (20.0%) randomized to placebo and in 2/54 (3.7%) randomized to BLF (RR: 0.19; RRR: 0.81; 95% CI for RR: 0.16-0.96; p = 0.026). In multivariable logistic regression analysis, there was no interaction between BLF treatment effect and type of feeding (p = 0.628). (B) In 1,891 infants not exclusively fed MM in our RCT of BLF and in the ELFIN RCT, BLF reduced the RR of LOS by 18% (RR: 0.82; 95% CI: 0.71-0.96; p = 0.01). CONCLUSION: Adequately powered studies should address the hypothesis that BLF is more effective in infants fed formula or donor milk than those fed MM. Such studies should evaluate whether a specific threshold of total lactoferrin intake can be identified to protect such patients from LOS.

Neonatal bacterial meningitis: a systematic review of European available data.

INTRODUCTION: Despite advances in neonatal intensive care and the improvements in surveillance, prevention and vaccination programs, neonatal meningitis still represents an important cause of morbidity and mortality in infants, with the highest mortality in the newborn population. The aim of this article was to summarize current knowledge about this topic with particular attention to management of neonatal meningitis in order to provide a useful tool for clinicians. EVIDENCE ACQUISITION: We reviewed the existent literature from five European Countries (France, German, Italy, Spain and UK) on the effectiveness of treatments for bacterial meningitis in newborns taking into consideration the antibiotic resistance phenomenon. EVIDENCE SYNTHESIS: There are few data available on this topic; bacterial neonatal meningitis treatment and management is currently based more on experience than on high quality evidences. CONCLUSIONS: Identification of the knowledge gaps may stimulate researchers to design new studies aiming to better define management strategies of bacterial meningitis in newborns.

COQ4 mutations cause a broad spectrum of mitochondrial disorders associated with CoQ10 deficiency.

Primary coenzyme Q10 (CoQ10) deficiencies are rare, clinically heterogeneous disorders caused by mutations in several genes encoding proteins involved in CoQ10 biosynthesis. CoQ10 is an essential component of the electron transport chain (ETC), where it shuttles electrons from complex I or II to complex III. By whole-exome sequencing, we identified five individuals carrying biallelic mutations in COQ4. The precise function of human COQ4 is not known, but it seems to play a structural role in stabilizing a multiheteromeric complex that contains most of the CoQ10 biosynthetic enzymes. The clinical phenotypes of the five subjects varied widely, but four had a prenatal or perinatal onset with early fatal outcome. Two unrelated individuals presented with severe hypotonia, bradycardia, respiratory insufficiency, and heart failure; two sisters showed antenatal cerebellar hypoplasia, neonatal respiratory-distress syndrome, and epileptic encephalopathy. The fifth subject had an early-onset but slowly progressive clinical course dominated by neurological deterioration with hardly any involvement of other organs. All available specimens from affected subjects showed reduced amounts of CoQ10 and often displayed a decrease in CoQ10-dependent ETC complex activities. The pathogenic role of all identified mutations was experimentally validated in a recombinant yeast model; oxidative growth, strongly impaired in strains lacking COQ4, was corrected by expression of human wild-type COQ4 cDNA but failed to be corrected by expression of COQ4 cDNAs with any of the mutations identified in affected subjects. COQ4 mutations are responsible for early-onset mitochondrial diseases with heterogeneous clinical presentations and associated with CoQ10 deficiency.

Exposure to Gastric Acid Inhibitors Increases the Risk of Infection in Preterm Very Low Birth Weight Infants but Concomitant Administration of Lactoferrin Counteracts This Effect.

OBJECTIVE: To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. STUDY DESIGN: This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. RESULTS: Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. CONCLUSION: Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. TRIAL REGISTRATION: isrctn.org: ISRCTN53107700.

Case report: acute clinical presentation and neonatal management of primary hyperparathyroidism due to a novel CaSR mutation.

BACKGROUND: Neonatal severe primary hyperparathyroidism (NSHPT) is a rare autosomal recessive disorder of calcium homeostasis, characterized by striking hyperparathyroidism, marked hypercalcemia and hyperparathyroid bone disease. We report the case of a newborn with a novel homozygous mutation of the CaSR, treated by successful subtotal parathyroidectomy, who had an acute presentation of the disease, i.e. out-of hospital cardiorespiratory arrest. . CASE PRESENTATION: A 8-day-old female newborn was admitted to the NICU of University of Bari "Aldo Moro" (Italy) after a cardiorespiratory arrest occurred at home. Severe hypercalcemia was found and different drug therapies were employed (Furosemide, Cinacalcet and bisphosphonate), as well as hyperhydration, until subtotal parathyroidectomy, was performed at day 32. Our patient's mutation was never described before so that a strict and individualized long-term follow-up was started. CONCLUSIONS: This case of NSHPT suggests that a near-miss event, labelled as a possible case of SIDS, could also be due to severe hypercalcemia and evidentiates the difficulties of the neonatal management of NSHPT. Furthermore, the identification of the specific CaSR mutation provides the substrate for prenatal diagnosis.