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.

The prenatal detection of distal tracheoesophageal fistulas in fetuses diagnosed with esophageal atresia.

BACKGROUND: Esophageal atresia is a major anomaly of varying severity. The complexity of surgical correction depends on the presence of a distal fistula. OBJECTIVE: This study aimed to determine the feasibility and accuracy of prenatal ultrasound detection of the distal fistula in fetuses diagnosed with esophageal atresia. STUDY DESIGN: This was an observational study conducted at a single tertiary care center between 2019 and 2021. Included were pregnant patients carrying a fetus prenatally diagnosed with esophageal atresia that was confirmed postnatally during corrective surgery or at postmortem autopsy. During the scan, the performing investigator determined the presence or absence of a distal fistula by scanning the location of the lower esophagus during fetal breathing. Cases in which the lower esophagus was observed distending with amniotic fluid during breathing were deemed "fistula present," and the remaining cases "fistula absent." Test feasibility and performance indices, including sensitivity, specificity, and positive and negative predictive value were calculated. The offline clips and images were reviewed by 2 investigators for the assessment of interoperator agreement using Cohen's Kappa formula. RESULTS: Included were 16 fetuses with esophageal atresia scanned between 2019 and 2021. All fetuses were successfully scanned with sufficient resolution of the area of interest during at least 3 cycles of breathing. It took a median of 8.5 minutes to determine the presence or absence of a distal fistula. The feasibility of the test was 100% (16/16). The test's sensitivity, specificity, and positive and negative predictive values were 80% (95% confidence interval, 55-100), 100% (95% confidence interval, 60-100), 100% (95% confidence interval, 65-100), and 75% (95% confidence interval, 45-100), respectively. The Cohen's Kappa for interoperator agreement was calculated to be 1, P<.001, corresponding to a "perfect" level of agreement. CONCLUSION: Distal fistulas in esophageal atresia can be demonstrated prenatally by targeted scanning using appropriate technique. The method provided is feasible, reproducible, and has excellent performance indices. This novel technique and observations may improve the prenatal diagnosis and counseling of esophageal atresia.

Preterm Singleton Birth Rate during the COVID-19 Lockdown: A Population-Based Study.

OBJECTIVE: The aim of the study is to evaluate the effect of the coronavirus disease 2019 (COVID-19) pandemic national lockdown period on the rate of singleton preterm births in Israel. STUDY DESIGN: This is a population-based cohort study of 3,41,291 singleton infants born in the months of January to July 2017 to 2020. Multivariable logistic regression analyses were used to estimate the influence of period and year on the rates of preterm births during the lockdown period (11th March - 5th May 2020) compared with rates before (January 1st 2020 - March 10th 2020), and after the lockdown (May 6th 2020-June 30th 2020) and to the corresponding periods in 2017to 2019. RESULTS: During the lockdown period the preterm birth rate (primary outcome) decreased by 9.7% from 5.05 to 4.56% in the pre-lockdown period (p = 0.006), an adjusted decrease of -0.52% (95% confidence interval -0.89%; -0.15%), odds ratio 0.898 (95% confidence interval 0.832; 0.970). CONCLUSION: The rate of singleton preterm births declined by 9.7% during the COVID-19 pandemic national lockdown period in Israel. KEY POINTS: · A 10% decline in all preterm deliveries was observed during the COVID-19 pandemic national lock-down period.. · The lock-down might influence environmental changes which contribute to the decrease in preterm deliveries.. · Changes in lifestyle, and societal behavior might contribute to the decrease in preterm deliveries..

Oesophageal atresia: sonographic signs may prenatally predict surgical complexity.

OBJECTIVE: Oesophageal atresia (OA) is a major anomaly of varying severity. The complexity of surgical correction highly depends on the gap length of missing oesophagus and the presence of a distal fistula. The aim of this study was to identify antenatal sonographic findings associated with presence of a distal fistula and type of surgical repair METHODS: Prenatal medical records of neonates postnatally diagnosed with OA were reviewed. Sonographic signs of OA (small/absent stomach, polyhydramnios, oesophageal pouch) and the trimester at sign detection were recorded and compared between (1) OA with and without a distal fistula and (2) early one-step versus delayed two-step anastomosis. Multivariate analysis was performed. RESULTS: Overall, 80 cases of OA were included. Absence of a distal fistula was significantly associated with higher rates of small/absent stomach (100% vs 28.6%, P<0.0001), oesophageal pouch (100% vs 24.3%, P<0.0001) and severe polyhydramnios (66.7% vs 22.9%, P=0.006), compared with OA with a distal fistula.Cases requiring a delayed two-step repair had higher rates of small/absent stomach (84.2% vs 16.7%, P>0.0001), severe polyhydramnios (47.4% vs 16.7%, P=0.008) and oesophageal pouch (73.7% vs 18.5%, P<0.0001), compared with those corrected in an early one-step anastomosis.Multivariate logistic regression found small/absent stomach and pouch to be significantly and independently associated with a delayed two-step anastomosis. CONCLUSION: OA without a distal fistula is associated with higher rates of prenatal sonographic signs. Both small/absent stomach and a pouch are independently associated with a delayed two-step anastomosis. These findings may help improve antenatal parental counselling regarding the anticipated surgical repair.

In-utero treatment of prenatal thoracic abnormalities by thoraco-amniotic shunts, short and long term neuro developmental outcome: A single center experience.

BACKGROUND: Severe primary fetal hydrothorax (PFH) and fetal lung lesions (FLL) such as congenital pulmonary airway malformation (CPAM) and Bronchopulmonary sequestration (BPS) are often treated by thoraco-amniotic shunt (TAS). OBJECTIVES: To compare short and long-term outcome of fetuses treated by TAS due to FLL to those treated due to PFH. METHOD: A retrospective analysis was performed for all fetuses treated by TAS, between the years 2004-2015, evaluating the short and long term neurodevelopmental outcome. Long term neurodevelopment was additionally analyzed prospectively by Vineland adaptive behavioral scale (VABS) standardized questionnaires. RESULTS: 38 fetuses were treated by 52 TAS insertions; of which 13 (35%) due to FLL and 25 due to PFH. Perinatal survival was high (87.9%) with 3 neonatal death and one termination of pregnancy (TOP). High survival rate persisted even in cases requiring recurrent shunt insertion (80% survival). There was no significant difference in short or long term outcome including perinatal survival (84% Vs 90%, P = 0.64) and hydrops resolution (91% Vs 63%, p = 0.19). Long term outcome, including rate of neurodevelopmental abnormalities (23.5% Vs 20%) and VABS score (91.3 ± 13.3 Vs 96.4 ± 14.7), were similar for both groups. CONCLUSION: TAS insertion is effective and resulting in high perinatal survival even in cases when sequential insertion is needed. Short and long- term outcome of neonates with FLL treated by TAS are comparable to neonates treated due to PFH.

Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy.

BACKGROUND: The exclusion of pregnant women from initial COVID-19 messenger RNA vaccine trials raised hesitancy regarding the benefits of vaccination for pregnant women, hence little is known about vaccines' efficacy in this population. OBJECTIVE: To determine the maternal-neonatal transplacental transfer of SARS-CoV-2 antibodies among vaccinated parturient women. A control group of COVID-19-recovered patients was included to compare the immunoglobulin G levels between vaccinated and recovered patients. STUDY DESIGN: This is a prospective cohort study conducted in a single tertiary medical center in Israel between February and March 2021; parturient women vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy were included and compared with COVID-19-recovered parturient women. SARS-CoV-2 immunoglobulin G antibodies were measured in maternal and cord sera, dried blood spot samples taken from newborns, and breast milk samples. The primary aim was to determine whether neonatal cord and dried blood spot samples were positive for SARS-CoV-2 antibodies and to evaluate the transfer ratio, defined as cord blood immunoglobulin G divided by maternal immunoglobulin G levels. RESULTS: The study included 64 vaccinated parturient women and 11 parturient women who had COVID-19 during pregnancy. All maternal blood sera samples and 98.3% of the cord blood sera samples were positive for SARS-Cov-2 immunoglobulin G with median concentrations of 26.1 (interquartile range, 22.0-39.7) and 20.2 (interquartile range, 12.7-29.0), respectively. Similarly, 96.4% of neonatal blood spot samples and all breast milk samples were positive for SARS-CoV-2 immunoglobulin G with median concentrations of 11.0 (interquartile range, 7.2-12.8) and 4.9 (interquartile range, 3.8-6.0), respectively. There was a significant positive correlation between maternal serum levels of SARS-CoV-2 immunoglobulin G and cord blood (r=0.483; P=.0001), neonatal blood spot (r=0.515; P=.004), and breast milk levels (r=0.396; P=.005) of SARS-CoV-2 immunoglobulin G. The median placental transfer ratio of SARS-COV-2 immunoglobulin G was 0.77. Comparison of vaccinated and recovered COVID-19 patients revealed significantly higher SARS-CoV-2 immunoglobulin G levels in maternal serum and cord blood among vaccinated women (P<.0001). CONCLUSION: Our study demonstrated the efficient transfer of SARS-CoV-2 immunoglobulin G across the placenta in women, vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy, to their neonates, with a positive correlation between maternal serum and cord blood antibody concentrations. In addition to maternal protection against COVID-19, the vaccine may also provide neonatal humoral immunity.

[THE CHALLENGE OF DIAGNOSING RARE LIFE THREATENING SKIN LESIONS].

INTRODUCTION: Skin lesions seen after delivery are frequent and mostly shallow, without the need for special care or diagnosis challenge. In the following case, an infant was born at 35 weeks gestation, presented after the delivery with a well-demarcated, necrotic plaque over the right forearm with neurologic deficit. The differential diagnosis includes life-threatening reasons, therefore, emergent laboratory and imaging tests were held. Treatment was given after consulting a multidisciplinary team of experts, including antibiotic treatment, blood products and anticoagulation and physiotherapy treatment was started. Under this treatment, improvement was noticed but there was still a motor restriction. He was discharged home on his 24th day of life, with the working diagnosis of Congenital Volkmann Ischemic Contracture (CVIC). On his seventh week of life, he arrived to the emergency room with focal seizure resulting from an infarct seen on an MRI. He was diagnosed with cerebral palsy at the age of five months. In conclusion, Congenital Volkmann Ischemic Contracture is a rare diagnosis, however, awareness is of importance since fast treatment is crucial for future prognosis.

[NECROTIZING ENTEROCOLITIS - AN ONGOING CHALLENGE].

INTRODUCTION: Necrotizing enterocolitis (NEC) is a major cause for morbidity and mortality among neonates, especially among low birth weight premature infants. Even though NEC has been highly investigated during the last few decades, understanding of the pathogenesis is still relatively poor. Throughout the years protective measures, as well as risk factors, were identified, but there is still no clear prevention strategy, and the percentage of neonates suffering of NEC was not changed. Moreover, the treatment approach is controversial in many circumstances other than a few clear surgical indications. The decision between conservative and surgical treatment in many situations is in the hands of the medical staff. Herein we present the story of a premature infant who suffered from feeding intolerance since birth, with major clinical deterioration after receiving packed red blood cells (PRBCs) transfusion. She was diagnosed with NEC and was treated conservatively, with clinical improvement and worsening alternately, until a colonic stricture was identified and treated surgically. We will provide a short review on risk factors, preventive measures, as well as the research regarding PRBCS transfusion and NEC development.

Increased risk for early hypertriglyceridemia in small for gestational age preterm infants.

Small for gestational age preterm are at increased risk for future metabolic syndrome. Early indication for the disrupted metabolism may be found in the perinatal period. We aimed to evaluate whether small for gestational age preterm infants are at increased risk for hypertriglyceridemia when treated with lipid emulsions, and to investigate the association between triglyceride levels and morbidity. Small for gestational age infants ≤ 34 weeks' gestation age born during 2013-2016 were matched and compared with appropriate for gestational age counterparts. Triglyceride concentration > 250 mg/dL during treatment with parenteral nutrition was considered high. The study included 71 pairs of preterm infants. Hypertriglyceridemia was documented among 22.5% of the small for gestational age infants vs. 5.6% of the appropriate for gestational age infants (p = 0.007). Mean triglyceride levels were 194.4 ± 192.3 mg/dL and 99.9 ± 82.8 mg/dL, respectively (p < 0.001). Small for gestational age was predictive of hypertriglyceridemia (OR = 6.41; 95% CI 1.8-22.9). No significant association was found between triglyceride levels and morbidities in multivariate analysis.Conclusion: Small for gestational age preterm infants receiving lipid emulsions might be at a higher risk for hypertriglyceridemia. Routine monitoring of triglyceride levels will enable identification of the necessity for a slower increase in lipid emulsion therapy. What is Known: • Moderate and very preterm infants are routinely treated with lipid emulsions. • Small for gestational age (SGA) infants may have different metabolism, as they demonstrate higher risk for metabolic syndrome. What is New: • • SGA infants had a higher mean triglyceride level and more commonly had early hypertriglyceridemia (triglycerides > 250 mg/dL) compared with appropriate for gestational age infants treated with the same intravenous lipid dose. Small for gestational age was predictive of hypertriglyceridemia. • No significant association was found between triglyceride levels and morbidities in multivariate analysis.

Esophageal atresia in twins compared to singletons: In utero manifestation and characteristics.

OBJECTIVE: Esophageal atresia with/without tracheo-esophageal fistula (EA/TEF) is more common among twins. The detection of polyhydramnios might be altered in twins, leading to EA/TEF underdiagnosis, prenatally. The aim of the study was to compare the prenatal manifestation of EA/TEF between twins and singletons. METHODS: A 12-year study of EA/TEF cases was performed at a tertiary center. Cases exhibiting (a) small/absent stomach or (b) polyhydramnios were considered "suspected"; cases with (c) esophageal pouch were considered "detected." We compared the rate and timing of appearance of these signs between the groups. RESULTS: There were 76 cases of EA/TEF, of which 17 were a co-twin. All twin pairs were EA/TEF discordant. The prevalence of EA/TEF at our center was 1:750 for twins (1:319 monochorionic and 1:1133 dichorionic) and 1:2399 for singletons. The rate of small/absent stomach, polyhydramnios and pouch in twins vs singletons was 23.5%, 47.1%, 29.4% and 39.7%, 72.4%,34.5%, respectively (P = .2, P = .09 and P = .7). Esophageal pouch was detected earlier in twins (P = .03). Twins were scanned more frequently (×1.8 times, P = .01). CONCLUSION: EA/TEF is more prevalent in twins. Despite lower rate of polyhydramnios, twins were similarly detected prenatally as singletons, and this was accomplished earlier in pregnancy; perhaps reflecting more frequent scans.

Short-Term Neonatal Outcome among Term Infants after In-Utero Exposure to Beta Blockers.

BACKGROUND: The need for postnatal monitoring of infants exposed to intrauterine beta blockers (BBs) has not been clearly defined. OBJECTIVES: To evaluate infants exposed to intrauterine BBs in order to estimate the need for postnatal monitoring. METHODS: This retrospective case-control study comprised 153 term infants born to mothers who had been treated with BBs during pregnancy. Treatment indications included hypertension 76 mothers (49.7%), cardiac arrhythmias 48 (31.4%), rheumatic heart disease 14 (9.1%), cardiomyopathy 11 (7.2%) and migraine 4 (2.6%). The controls were infants of mothers with hypertension not exposed to BBs who were born at the same gestational age and born closest (before or after) to the matched infant in the study group. RESULTS: Compared to the control group, the infants in the study group had a higher prevalence of early asymptomatic hypoglycemia (study 30.7% vs. control 18.3%, P = 0.016), short symptomatic bradycardia events, other cardiac manifestations (P = 0.016), and longer hospitalization (P < 0.001). No life-threatening medical conditions were documented. The birth weight was significantly lower for the high-dose subgroup compared to the low-dose subgroup (P = 0.03), and the high-dose subgroup had a higher incidence of small-for-gestational-age (P = 0.02). CONCLUSIONS: No alarming or life-threatening medical conditions were observed among term infants born to BB treated mothers. These infants can be safely observed for 48 hours after birth close to their mothers in the maternity ward. Glucose follow-up is needed, especially in the first hours of life.

"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.

Internal and External Resources and the Adjustment of Parents of Premature Infants.

Studies have shown premature birth and infant hospitalization to be associated with increased levels of parental distress. Internal and external psychological resources have been found to mitigate distress among persons coping with stressful medical events. The current study evaluated psychological resources and distress in 87 parents (57 mothers and 30 fathers) to whom an infant was born prematurely and hospitalized in the NICU of a large tertiary medical center. Parents were administered standardized measures of internal (problem-solving skills) and external (total spousal support, adequacy of spousal support) psychological resources and of psychological distress (depression, posttraumatic symptoms, and mood). Findings indicated that higher levels of problem-solving skills and more adequate spousal support, but not total spousal support, were related to lower levels of parental distress. Adequacy of spousal support and parents' problem-solving skills accounted for 18% of the variance in overall mood and 13.8% of the variance in posttraumatic stress symptoms. A significant two-way interaction was found between adequacy of spousal support and problem-solving skills such that individuals with better problem-solving skills reported better overall mood independent of the adequacy of spousal support they receive. However, for individuals with poor problem-solving skills, the adequacy of the spousal support they receive was a significant factor in determining their overall mood. The theoretical and clinical implications of these findings are discussed in terms of the accessibility of these resources to assessment and their potential for change via existing intervention approaches.

Infants Born with Esophageal Atresia with or without Tracheo-Esophageal Fistula: Short- and Long-Term Outcomes.

BACKGROUND: The estimated incidence of esophageal atresia (EA) with or without tracheo-esophageal fistula (TEF) is 1:3500 live births. During childhood these patients have various co-morbidities, but the overall quality of life among adults is similar to that of the general population. OBJECTIVES: To evaluate short- and long-term co-morbidities and quality of life among infants born with EA ± TEF at a large single medical center. METHODS: Medical records of 65 children born over a 21 year period were reviewed for short- and long-term medical data. Telephone interviews were conducted with 46 of their parents regarding medical problems and quality of life after home discharge. RESULTS: The main long-term co-morbidities during the first 2 years of life, 4-6 years of age, and during adolescence (12-16 years) included gastro-esophageal reflux disease (GERD) in 56.5%, 35.8%, and 18.7%, respectively; stridor in 84.8%, 45.2%, and 12.5%, respectively; hyper-reactive airway disease (HRAD) in 43.5%, 35.5%, and 36.5%, respectively; recurrent pneumonia in 43.5%, 32.3%, and 18.8%, respectively; and overall recurrent hospitalizations in 87%, 41.9%, and 25%, respectively. The quality of life was reportedly affected among 100%, 75%, and 33.3% respectively. CONCLUSIONS: Long-term follow-up of patients with EA ± TEF indicates a high burden of co-morbidities during the first 6 years of life, with a gradual decrease in symptoms thereafter. Nevertheless, HRAD continued to impact the daily life of about one-third of the older adolescents, and GERD one-fifth. A long-term multidisciplinary follow-up should be conducted to prevent late onset complications that may affect the quality of life.

Risk factors for brain damage among preterm twins.

AIM: To evaluate the perinatal and postnatal risk factors for various brain pathologies among preterm twins. METHODS: Retrospective data of 104 twin pairs of which one of the siblings had evidence of abnormal head ultrasound (HUS) and its co-twin with normal HUS served as control. RESULTS: Abnormal HUS consisted of periventricular echodensities among 69 infants, intraventricular hemorrhage among 28 infants, cystic periventricular leukomalacia among 10 infants, and other parenchymal brain pathologies among 5 infants. Perinatal and postnatal complications were similar between study and controls. Siblings with severe brain pathologies were ventilated for longer time over their co-twins. In 10 out of 11 cases of discordant twins (≥20%) with severe brain pathology, the severe pathology was recorded in the larger sibling. CONCLUSIONS: Our study results, which included matched preterm twin pairs for study/control groups to evaluate risk factors for the overall evidence of brain injury, could not determine specific risk factors for these brain pathologies. The finding that severe brain pathologies were more common among the larger co-twin requires further study of and attention to short- and long-term outcomes and the potential conflicts that may arise.

Direct Feeding at the Breast Is Associated with Breast Milk Feeding Duration among Preterm Infants.

BACKGROUND: In spite of high rates of initiating breast milk feeding (BMF) among preterm infants, a significant rate of discontinuation occurs shortly after discharge. AIM: To investigate the effect of mode (direct feeding at the breast vs. expressing) and exclusivity (breast milk combined with formula vs. breast milk only) as well as maternal perceptions on the duration of BMF among preterm infants. METHODS: The study included mothers whose infants were born before 32 weeks gestation, between January 2012 and August 2015 at Sheba Medical Center (SMC). Perinatal data were collected retrospectively from infants' computerized charts. Mothers were approached >12 months postpartum and were asked to complete a questionnaire. Those who agreed to participate were asked (during their visit to the follow-up clinic or by phone or mail) to complete a questionnaire regarding mode and duration of BMF as well as reasons for its discontinuation. Mothers were also asked about their pre-partum intentions to feed directly at the breast. RESULTS: Out of 162 eligible mothers, 131 (80.8%) initiated BMF during their intensive care unit (ICU) hospitalization. Of these, 66 (50.3%) discontinued BMF earlier than six months postpartum. BMF ≥ 6 months was significantly associated with direct feeding at the breast, duration of exclusive BMF, and singleton birth. Regression analysis revealed that direct feeding at the breast (any or only) and duration of BMF exclusivity were the only significant variables associated with BMF duration (Odds ratio (OR) 5.5 and 95% confidence interval (CI) 2.00-15.37; OR 1.5 and 95% CI 1.25-1.88, respectively). Milk supply (inadequate or nonexistent) was the most commonly reported cause for BMF discontinuation <6 months. Direct feeding at the breast was significantly associated with BMF duration and was more common among singletons. CONCLUSIONS: Direct feeding at the breast and duration of exclusive BMF are associated with duration of BMF among infants born <32 weeks of gestational age (GA). These findings suggest that targeting these two factors may play a key role in prolonging BMF duration among preterm infants.

Sex-Specific Life Course Changes in the Neuro-Metabolic Phenotype of Glut3 Null Heterozygous Mice: Ketogenic Diet Ameliorates Electroencephalographic Seizures and Improves Sociability.

We tested the hypothesis that exposure of glut3+/- mice to a ketogenic diet ameliorates autism-like features, which include aberrant behavior and electrographic seizures. We first investigated the life course sex-specific changes in basal plasma-cerebrospinal fluid (CSF)-brain metabolic profile, brain glucose transport/uptake, glucose and monocarboxylate transporter proteins, and adenosine triphosphate (ATP) in the presence or absence of systemic insulin administration. Glut3+/- male but not female mice (5 months of age) displayed reduced CSF glucose/lactate concentrations with no change in brain Glut1, Mct2, glucose uptake or ATP. Exogenous insulin-induced hypoglycemia increased brain glucose uptake in glut3+/- males alone. Higher plasma-CSF ketones (ß-hydroxybutyrate) and lower brain Glut3 in females vs males proved protective in the former while enhancing vulnerability in the latter. As a consequence, increased synaptic proteins (neuroligin4 and SAPAP1) with spontaneous excitatory postsynaptic activity subsequently reduced hippocampal glucose content and increased brain amyloid ß1-40 deposition in an age-dependent manner in glut3+/- males but not females (4 to 24 months of age). We then explored the protective effect of a ketogenic diet on ultrasonic vocalization, sociability, spatial learning and memory, and electroencephalogram seizures in male mice (7 days to 6 to 8 months of age) alone. A ketogenic diet partially restored sociability without affecting perturbed vocalization, spatial learning and memory, and reduced seizure events. We conclude that (1) sex-specific and age-dependent perturbations underlie the phenotype of glut3+/- mice, and (2) a ketogenic diet ameliorates seizures caused by increased cortical excitation and improves sociability, but fails to rescue vocalization and cognitive deficits in glut3+/- male mice.

A combined one-stage surgical approach of orbital tumor debulking, lid reconstruction, and ptosis repair in children with orbitotemporal neurofibromatosis.

BACKGROUND AND AIM: To describe a series of children with neurofibromatosis type 1 (NF1) and a plexiform neurofibroma of the orbit with ptosis who underwent a combined one-stage surgery for tumor debulking, lid reconstruction, and ptosis repair. METHODS: A retrospective review of 6 cases of combined one-step surgeries for orbital plexiform neurofibroma with ptosis. RESULTS: The study included 6 children (4 boys, mean age 3.4 years). Follow-up time was at least 9 months. All children had unilateral orbitofacial plexiform. All children underwent a combined one-stage surgery performed by a single surgeon for tumor debulking, lid reconstruction, and ptosis repair. There was significant improvement in upper lid height and lid contour postoperatively in all the patients. One patient had early recurrence and underwent another two surgeries in the following years. CONCLUSION: A combined surgical approach for orbital involvement in NF1 results in favorable immediate results, though late recurrence may require additional surgical interventions in the future.

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.

Short-Term Perinatal Outcome among Term Infants with Prenatal Diagnosis of Large Abdominal Circumference.

Background Measuring fetal abdominal circumference (AC) prenatally is an effective tool for predicting neonatal weight and macrosomia. Data are lacking regarding the outcome of newborn infants with prenatal diagnosis of large AC. Aim The aim of this study was to evaluate early short-term neonatal outcome among term singleton newborn infants with prenatal diagnosis of large AC. Methods Retrospective data were collected on 501 term infants with prenatal diagnosis of large AC (≥ 360 mm) and on matched controls, including information on maternal condition and on infant perinatal complications. Results In compare with controls, the study group had higher incidence of macrosomia (188 [37.5%] vs. 18 [3.6%], p < 0.001), hypoglycemia (48 (9.6%) vs. 25 [5%], p = 0.007), and significant morbidity (49 [9.8%] vs. 28 [5.6%], p = 0.017) but without increased incidence of congenital malformations or other perinatal complications. Only among the macrosomic, study subgroup and their controls differences were recorded including hypoglycemia (17.6 vs. 4.8%, p < 0.001), need for oral glucose (11.2 vs. 2.7%, p = 0.002), significant morbidity (10.1 vs. 3.7%, p = 0.024), and hospitalization in special care unit (11.7 vs. 4.3%, p = 0.012). Conclusion Prelabor diagnosis of large AC mostly reflects the infant's high birth weight and macrosomia with the associated perinatal complications. Large AC by itself was not predictive of any congenital malformations or perinatal and postnatal complications.