Protective Characteristics of Human Breast Milk on Early Childhood Otitis Media: A Narrative Review.

Introduction: Human breast milk (HBM) contains a complex and dynamically changing variety of factors that contribute to the infant's developing immune system's ability to fight upper respiratory tract infections, including otitis media (OM). We sought to summarize the current evidence on the protective characteristics of HBM, through direct or donated feeding, toward early childhood OM. Methods: For this narrative review, we performed a literature search on OM in the context of HBM feeding in the PubMed, Embase, and Google Scholar databases, between January 1, 2008, and July 1, 2023. Results: Immunoglobulin A (IgA) provides a short-term immunity of 2-3 days against otopathogens causing OM. IgA-mediated immunity is effective against OM up to 7 months of age if breastfeeding continues. The role of transferred IgM and IgG in HBM is unclear. Although there is a potential protective value of microRNA, hormones, oligosaccharides, stem cells, and interleukins present in HBM, their role is unclear. Any duration of breastfeeding is superior to no breastfeeding in OM risk reduction, with a big variability among studies (odds ratio 0.23-0.81, depending on the duration). Duration of breastfeeding ≥6 months was found to be the most effective in OM risk reduction, but there was no evidence of continued benefits after 2 years of age. Expressed breastfeeding was not shown to be more beneficial. The protective values of donor HBM against OM are still undetermined. Conclusion: HBM has numerous components that contribute to protection against early childhood OM.

National Rapid Genome Sequencing in Neonatal Intensive Care.

Importance: National implementation of rapid trio genome sequencing (rtGS) in a clinical acute setting is essential to ensure advanced and equitable care for ill neonates. Objective: To evaluate the feasibility, diagnostic efficacy, and clinical utility of rtGS in neonatal intensive care units (NICUs) throughout Israel. Design, Setting, and Participants: This prospective, public health care-based, multicenter cohort study was conducted from October 2021 to December 2022 with the Community Genetics Department of the Israeli Ministry of Health and all Israeli medical genetics institutes (n = 18) and NICUs (n = 25). Critically ill neonates suspected of having a genetic etiology were offered rtGS. All sequencing, analysis, and interpretation of data were performed in a central genomics center at Tel-Aviv Sourasky Medical Center. Rapid results were expected within 10 days. A secondary analysis report, issued within 60 days, focused mainly on cases with negative rapid results and actionable secondary findings. Pathogenic, likely pathogenic, and highly suspected variants of unknown significance (VUS) were reported. Main Outcomes and Measures: Diagnostic rate, including highly suspected disease-causing VUS, and turnaround time for rapid results. Clinical utility was assessed via questionnaires circulated to treating neonatologists. Results: A total of 130 neonates across Israel (70 [54%] male; 60 [46%] female) met inclusion criteria and were recruited. Mean (SD) age at enrollment was 12 (13) days. Mean (SD) turnaround time for rapid report was 7 (3) days. Diagnostic efficacy was 50% (65 of 130) for disease-causing variants, 11% (14 of 130) for VUS suspected to be causative, and 1 novel gene candidate (1%). Disease-causing variants included 12 chromosomal and 52 monogenic disorders as well as 1 neonate with uniparental disomy. Overall, the response rate for clinical utility questionnaires was 82% (107 of 130). Among respondents, genomic testing led to a change in medical management for 24 neonates (22%). Results led to immediate precision medicine for 6 of 65 diagnosed infants (9%), an additional 2 (3%) received palliative care, and 2 (3%) were transferred to nursing homes. Conclusions and Relevance: In this national cohort study, rtGS in critically ill neonates was feasible and diagnostically beneficial in a public health care setting. This study is a prerequisite for implementation of rtGS for ill neonates into routine care and may aid in design of similar studies in other public health care systems.

Newborn Hearing Screening: Early Ear Examination Improves the Pass Rate.

BACKGROUND: Temporary conductive hearing loss due to vernix accumulation in the external ear canal may lead to a false-positive result in newborn hearing screening tests. The aim of this study was to evaluate whether ear examination and intervention may reduce the false-positive rate prior to hospital discharge. METHODS: A case series of 42 newborns who failed initial otoacoustic emissions screening were studied in our institution between May and December 2020. RESULTS: During the study period, a total of 735 neonates (1470 ears) were screened by otoacoustic emissions in our hospital. Forty-two newborns who failed otoacoustic emissions were included in our study. They constituted 3.9% (n=58 ears) of the total number of ears screened. Forty-four ears (75.9%) passed and 14 ears (24.1%) failed otoacoustic emissions rescreening performed shortly following vernix cleaning. Twelve of the remaining 14 ears passed at 10-day rescreening. The remaining 2 ears presented true bilateral hearing loss. During the study period, the general false-positive rate decreased from 56/735 (7.61%) to 12/735(1.63%) (P < .00001). CONCLUSION: Cleaning the vernix of infants who failed otoacoustic emissions prior to hospital discharge lowers the false-positive rate of universal neonatal hearing screening. We may assume that vernix cleaning will reduce significant healthcare workload, costs of unnecessary investigations, as well as parental anxiety.

"Golden Hour" quality improvement intervention and short-term outcome among preterm infants.

OBJECTIVE: To evaluate the impact of a quality improvement intervention during the first hour of life ("Golden Hour") on short-term preterm neonatal outcome. STUDY DESIGN: A comprehensive protocol designed for initial stabilization and treatment of preterm infants that included cord blood sampling, use of a dedicated resuscitation room and improved team communication using Crew Resource Management tools. The infants admitted before and after implementation of the protocol were retrospectively compared in a matched case-control design. RESULTS: There were 194 infants in the intervention group and 194 controls. Admission temperatures improved significantly from a mean of 35.26 °C to 36.26 °C (P < 0.001), and late-onset sepsis and bronchopulmonary dysplasia rates lowered significantly (P = 0.035 and P = 0.028, respectively) in the intervention group. There was trend towards reduction in early blood transfusion and ventilation duration. CONCLUSIONS: A "Golden Hour" quality improvement intervention was of significant benefit for preterm neonates. Further follow-up to assess long-term effects is warranted.

Risk factors for periventricular echodensities and outcomes in preterm infants.

OBJECTIVES: To determine the incidence, risk factors and outcomes associated with transient and/or persistent periventricular echodensities (PVED) among preterm infants. METHODS: Medical records of preterm infants born at ≤ 32 weeks gestational age (GA) with PVED and no other brain pathology were reviewed and compared to matched control infants in a case-controlled retrospective study. Neurodevelopmental outcomes at 8-24 months corrected age were documented. RESULTS: A 17.8% incidence of PVED was recorded, with the highest incidence of 30-40% recorded at 29-31 weeks GA. Study and control groups were similar for all maternal parameters and neonatal morbidities, except for a higher incidence of respiratory distress syndrome among the study group. PVED at one month of age was predicted by 5 min Apgar score < 7 [OR = 33.78 (CI 2.94-388.06, p = 0.005)]. PVED was not associated with long-term neurodevelopmental disability. CONCLUSIONS: No risk factors or specific associated morbidities were identified among preterm infants with transient PVED. PVED at one month of age was predicted by low 5 min Apgar scores, possibly suggesting different pathogenesis or timing between the groups. Long-term outcome studies are needed to determine PVED impact.

Applying Judgment Analysis Theory and Methods to Obtain an Insight Into Clinical Judgments: Implementation and Findings With a Simulated Neonatal Intensive Care Unit Setup.

INTRODUCTION: Clinicians who provide acute care are required to quickly identify and judge the illness severity of patients who experience deterioration in their clinical state. Accuracy of judgments can only be tested with respect to a valid reference, but in most health care areas, there is no such score. Judgment analysis theory and methods are presented and proposed as a framework to obtain insight into clinical judgments. A study in a simulated neonatal intensive care unit setup is described to demonstrate the applicability of the proposed methodology. METHODS: Sixteen participants from a neonatal intensive care unit department reviewed 31 clips of simulated cases. The participants were directed to use a 5-point scale to rate their personal interpretation regarding the illness severity of the simulated patient. Judgment analysis techniques were used to identify the judgment capabilities of the participants and to determine factors that influence those capabilities. RESULTS: Most participants interpreted the clinical signs information consistently, but interpretation varied remarkably between clinicians, providing possible explanation to the differences between the clinicians' judgments. Significant correlations were found between the doctors' years of medical experience and attributes of their judgments. CONCLUSIONS: Judgment analysis can be used to obtain insight into clinical judgments and to identify and quantify factors that affect clinicians' judgments. Judgment analysis can promote health care by enhancing clinical assessment teaching, by providing objective and personalized feedback to team members about their judgment performance, and by introducing a unified and objective method to study elements that affect clinical judgments.

Gestational weight gain and body mass indexes have an impact on the outcomes of diabetic mothers and infants.

AIM: This study evaluated mothers with diabetes to determine whether prepregnancy body mass index (BMI), BMI on delivery or gestational weight gain (GWG) had the greatest impact on maternal and neonatal outcomes. METHODS: We retrospectively examined the medical charts of 634 full-term infants born to mothers with gestational diabetes mellitus not requiring insulin (n = 476), gestational diabetes mellitus requiring insulin (n = 140) and insulin-dependent diabetes mellitus (n = 18). Data regarding maternal BMI before pregnancy and on delivery were recorded, as well as maternal and neonatal complications. RESULTS: Infants born to women who gained more than the recommended weight during pregnancy had higher birthweights, higher rates of meconium-stained amniotic fluid and neonatal hypoglycaemia. Using logistic regression, Caesarean section delivery was predicted by gestational diabetes requiring insulin, with an odds ratio (OR) of 1.76, maternal hypertension (OR 2.4), infants born large for gestational age (OR 2.78) and maternal BMI ≥ 30 on delivery (OR 1.06). Neonatal complications were predicted by maternal insulin-dependent diabetes (OR 5.21), lower gestational age (OR 0.8) and GWG above the recommended amount (OR 1.56). CONCLUSION: Women with diabetes should be made aware that higher GWG can lead to Caesarean section delivery, infant macrosomia and other neonatal complications.

Macrocephaly-capillary malformation presenting with fetal arrhythmia.

Macrocephaly-capillary malformation (OMIM 602501) is a rare overgrowth and asymmetry syndrome. Cardiac arrhythmias were reported to occur in few patients. We present a case in which fetal arrhythmia was the presenting symptom of the syndrome.

Outbreak of life-threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula.

OBJECTIVE: Between October and November 2003, several infants with encephalopathy were hospitalized in pediatric intensive care units in Israel. Two died of cardiomyopathy. Analysis of the accumulated data showed that all had been fed the same brand of soy-based formula (Remedia Super Soya 1), specifically manufactured for the Israeli market. The source was identified on November 6, 2003, when a 5.5-month-old infant was admitted to Sourasky Medical Center with upbeat nystagmus, ophthalmoplegia, and vomiting. Wernicke's encephalopathy was suspected, and treatment with supplementary thiamine was started. His condition improved within hours. Detailed history revealed that the infant was being fed the same formula, raising suspicions that it was deficient in thiamine. The formula was tested by the Israeli public health authorities, and the thiamine level was found to be undetectable (<0.5 microg/g). The product was pulled from the shelves, and the public was alerted. Thiamine deficiency in infants is very rare in developed countries. The aim of this study was to report the epidemiology of the outbreak and to describe the diagnosis, clinical course, and outcome of 9 affected infants in our care. METHODS: After the index case, an additional 8 infants were identified in our centers by medical history, physical examination, and laboratory testing. The group consisted of 6 male and 3 female infants aged 2 to 12 months. All were assessed with the erythrocyte transketolase activity assay, wherein the extent of thiamine deficiency is expressed in percentage stimulation compared with baseline (thiamine pyrophosphate effect [TPPE]). Normal values range from 0% to 15%; a value of 15% to 25% indicates thiamine deficiency, and >25% indicates severe deficiency. Blood lactate levels (normal: 0.5-2 mmol/L) were measured in 6 infants, cerebrospinal fluid lactate in 2 (normal: 0.5-2 mmol/L), and blood pyruvate in 4 (normal: 0.03-0.08 mmol/L). The diagnostic criteria for thiamine deficiency were abnormal transketolase activity and/or unexplained lactic acidosis. Treatment consisted of intramuscular thiamine 50 mg/day for 14 days combined with a switch to another infant formula. RESULTS: Early symptoms were nonspecific and included mainly vomiting (n = 8), lethargy (n = 7), irritability (n = 5), abdominal distension (n = 4), diarrhea (n = 4), respiratory symptoms (n = 4), developmental delay (n = 3), and failure to thrive (n = 2). Infection was found in all cases. Six infants were admitted with fever. One patient had clinical dysentery and group C Salmonella sepsis; the others had mild infection: acute gastroenteritis (n = 2); upper respiratory infection (n = 2); and bronchopneumonia, acute bronchitis, and viral infection (n = 1 each). Two infants were treated with antibiotics. Three infants had neurologic symptoms of ophthalmoplegia with bilateral abduction deficit with or without upbeat nystagmus. All 3 had blood lactic acidosis, and 2 had high cerebrospinal fluid lactate levels. Patient 1, our index case, was hospitalized for upbeat nystagmus and ophthalmoplegia, in addition to daily vomiting episodes since 4 months of age and weight loss of 0.5 kg. Findings on brain computed tomography were normal. Blood lactate levels were high, and TPPE was 37.8%. Brain magnetic resonance imaging (MRI) revealed no abnormalities. Patient 2, who presented at 5 months with lethargy, vomiting, grunting, and abdominal tenderness, was found to have intussusception on abdominal ultrasound and underwent 2 attempts at reduction with air enema several hours apart. However, the lethargy failed to resolve and ophthalmoplegia appeared the next day, leading to suspicions of Wernicke's encephalopathy. Laboratory tests showed severe thiamine deficiency (TPPE 31.2%). In patients 1 and 2, treatment led to complete resolution of symptoms. The third infant, a 5-month-old girl, was admitted on October 10, 2003, well before the outbreak was recognized, with vomiting, fever, and ophthalmoplegia. Her condition deteriorated to seizures, apnea, and coma. Brain MRI showed a bilateral symmetrical hyperintense signal in the basal ganglia, mamillary bodies, and periaqueductal gray matter. Suspecting a metabolic disease, vitamins were added to the intravenous solution, including thiamine 250 mg twice a day. Clinical improvement was noted 1 day later. TPPE assay performed after treatment with thiamine was started was still abnormal (17.6%). Her formula was substituted after 4 weeks, after the announcement about the thiamine deficiency. Although the MRI findings improved 5 weeks later, the infant had sequelae of ophthalmoplegia and motor abnormalities and is currently receiving physiotherapy. All 3 patients with neurologic manifestations were fed exclusively with the soy-based formula for 2 to 3.5 months, whereas the others had received solid food supplements. Longer administration of the formula (ie, chronic thiamine deficiency) was associated with failure to thrive. For example, one 12-month-old girl who received the defective formula for 8 months presented with refusal to eat, vomiting, failure to thrive (75th to <5th percentile), hypotonia, weakness, and motor delay. Extensive workup was negative for malabsorption and immunodeficiency. On admission, the patient had Salmonella gastroenteritis and sepsis and was treated with antibiotics. After thiamine deficiency was diagnosed, she received large doses of thiamine (50 mg/day) for 2 weeks. Like the other 5 infants without neurologic involvement, her clinical signs and symptoms disappeared completely within 2 to 3 weeks of treatment, and TPPE levels normalized within 1 to 7 days. There were no side effects. As part of its investigation, the Israel Ministry of Health screened 156 infants who were fed the soy-based formula for thiamine deficiency. However, by that time, most were already being fed alternative formulas and had begun oral thiamine treatment. Abnormal TPPE results (>15%) were noted in 8 infants, 3 male and 5 female, all >1 year old, who were receiving solid food supplements. Although their parents failed to notice any symptoms, irritability, lethargy, vomiting, anorexia, failure to thrive, and developmental delay were documented by the examining physicians. None had signs of neurologic involvement. Treatment consisted of oral thiamine supplements for 2 weeks. CONCLUSIONS: Clinician awareness of the possibility of thiamine deficiency even in well-nourished infants is important for early recognition and prevention of irreversible brain damage. Therapy with large doses of thiamine should be initiated at the earliest suspicion of vitamin depletion, even before laboratory evidence is available and before neurologic or cardiologic symptoms appear.