Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures.

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.

The association of intrapartum deceleration and acceleration areas with MRI findings in neonatal encephalopathy.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is an important contributor to disability worldwide. The current cardiotocography (CTG) predictive value for neonatal outcome is limited. OBJECTIVE: To assess the association of intrapartum CTG deceleration and acceleration areas with early MRI cerebral pathology in infants with HIE. METHODS: Term and near-term low-risk pregnancies that resulted in HIE, treated with therapeutic hypothermia with sufficient CTG records from a single, tertiary hospital between 2013 and 2021 were enrolled. Accelerations and decelerations areas, their minimum and maximum depths, and duration were calculated as well as the acceleration-to-deceleration area ratio during the 120 min prior to delivery. These data were assessed for associations with higher degrees of abnormality on early MRI scans. RESULTS: A total of 77 infants were included in the final analysis. Significant associations between increased total acceleration area (p = 0.007) and between a higher acceleration-to-deceleration area ratio (p = 0.003) and better MRI results were detected. CONCLUSION: In neonates treated for HIE, acceleration area and acceleration-to-deceleration ratio are associated with the risk of neonatal brain MRI abnormalities. To increase the role of these measurements as a relevant clinical tool, larger, more powered prospective trials are needed, using computerized real-time analysis. IMPACT: The current cardiotocography predictive value for neonatal outcome is limited. This study aimed to assess the association of intrapartum deceleration and acceleration areas with the degree of cerebral injury in early cerebral MRI of neonates with encephalopathy. Lower acceleration area and acceleration-to-deceleration ratio were found to be associated with a higher degree of neonatal brain injury. Brain MRI is a marker of long-term outcome; its association with cardiotocography indices supports their association with long-term outcome in these neonates. Future computer-based CTG area analysis could assist in delivery room decision making to better time interventions and prevent hypoxic-ischemic encephalopathy.

The impact of the early onset neonatal sepsis calculator on antibiotic initiation: a single center study in Israel.

To evaluate the effect of implementation of the Kaiser Permanente (KP) early onset sepsis (EOS) calculator in infants born at 34 week's gestation or more on antibiotic utilization and length of hospitalization. A single center, retrospective cohort study included all neonates born in Soroka Medical Center at 34 weeks gestation or more between January 1st, 2015, and January 1st, 2019, with a predefined maternal risk factor for EOS. Two cohorts of neonates were compared during two time periods, before and after the implementation of the KP calculator. Multivariable logistic and linear regressions were performed to assess the effect of the KP calculator on antibiotic treatment and length of hospitalization. Also, an interrupted time series (ITS) analysis was used to assess the time trends of the two periods. The study included 3858 neonates in the pre-implementation period and 3081 neonates in the post-implementation cohort. The use of the calculator resulted in a significant reduction (46%) in antibiotics treatment for suspected EOS (5.1 vs. 9.4%, P < 0.001). The ITS analysis demonstrated a sharp decline in the slope of antibiotic treatment in the post intervention period: (b = -0.14, p-value = 0.08). The length of hospitalization was significantly reduced in the post-implementation cohort from 62 to 60 h (p-value < 0.001) with no clinical significance. The incidence of EOS was similar in both groups.    Conclusion: A significant reduction in antibiotic treatment was demonstrated after the implementation of the KP calculator without an increase incidence of EOS. The calculator is a powerful accessory decision-making tool that can be used safely in combination with, but not replacing, thorough clinical assessment. What is Known: • The EOS calculator is a useful tool that leads to a significant reduction in preemptive antibiotic utilization. What is New: • The EOS calculator is sensitive when applied to the whole-nursery. • The calculator is useful in different populations, also when women are not routinely screened for GBS.

Association Between Neonatal Phototherapy Exposure and Childhood Neoplasm.

OBJECTIVE: To study the association between phototherapy for the treatment of neonatal jaundice and the risk of childhood neoplasms. STUDY DESIGN: This population-based retrospective cohort study included all infants born at ≥32 weeks of gestation at a single medical center between 1988 and 2018. The incidence of neoplastic diseases was compared between infants exposed to phototherapy and those unexposed. Kaplan-Meier curves and log-rank tests were used for cumulative incidence comparison, and multivariable Cox and Weibull survival analysis were used to adjust for confounding or clinically significant variables. RESULTS: The study population included 342 172 infants, of whom 18 797 (5.5%) were exposed to phototherapy. The median duration of follow-up was 9.5 years (range, birth to 18 years). Phototherapy was associated with a significantly increased risk for childhood malignancies and benign tumors (preterm birth and maternal age-adjusted hazard ratio, 1.89 [95% CI, 1.35-2.67] for malignancies and 1.27 [95% CI, 1.02-1.57] for benign tumors) Specifically, phototherapy was associated with hematopoietic cancers and leukemia (hazard ratio, 2.29 [95% CI, 1.48-3.54; P < .01] for hematopoietic cancers and 2.51 [95% CI, 1.52-4.14; P < .001] for leukemia), but not with solid tumors and lymphoma. CONCLUSIONS: Phototherapy may be associated with a slightly increased childhood risk of neoplasm. It is important to strictly follow phototherapy treatment guidelines to minimize unnecessary exposure.

Early versus late-onset necrotizing enterocolitis in very low birth infants in the neonatal intensive care unit.

BACKGROUND: Necrotizing enterocolitis (NEC), one of the most severe emergencies in neonates, is a multifactorial disease with diverse risk factors. OBJECTIVES: To compare between the clinical and laboratory characteristics of premature infants diagnosed with early-onset NEC (EO-NEC) and those with late-onset NEC (LO-NEC). PATIENTS AND METHODS: Enrolled infants were identified from prospective local data collected for the Israel National very low birth weight (VLBW, < 1500 g) infant database and from the local electronic patient files data base for the period 1996-2017. RESULTS: Overall, 95 VLBW infants (61, 64.21% EO-NEC and 34, 35.87% LO-NEC) were enrolled. EO-NEC infants had higher rate of IVH grade 3 and 4 (26.2% vs 2.9%, p = 0.005) and were more likely to undergo surgery (49.2% vs 26.5%, p = 0.031). LO-NEC infants had a higher incidence of previous bloodstream infections (35.3% vs 8.2%, p = 0.002) compared to EO-NEC. In multivariable analysis models, surgical intervention was associated with EO-NEC (OR: 4.627, p = 0.013) as well as PDA and positive blood culture prior to the NEC episode. CONCLUSIONS: Our data support the hypothesis that EO-NEC has significant different clinical and microbiological attributes compared to LO-NEC.

Appearance of sleep cycling after birth in term neonates: an electro-physiologic study.

BACKGROUND: Appearance of sleep cycling has been associated with good outcome in term and preterm infants, but the normal time of its appearance has not been determined. The objectives of this study were, to correlate the time of sleep cycling appearance and the length of quiet sleep in neonates with different degrees of mild perinatal stress. METHODS: Three groups of term infants recorded with aEEG after birth were studied: infants delivered by planned cesarean section (group 1), infants with mild perinatal stress (group 2) and infants with mild neonatal encephalopathy (group 3). Groups were correlated with the appearance and length of quiet sleep. RESULTS: In all, 132 infants were assessed. Quiet sleep appearance differed significantly between groups (p < 0.001). All infants in group 1 developed quiet sleep before the age of 6 h compared to 81% in group 2 and 52% in group 3 (p < 0.001). No differences in the quiet sleep length was found between groups. Belonging to group 3 (p < 0.001) and 1-min Apgar score (p = 0.002) significantly predicted a delay in appearance of the first quiet sleep period. Cesarean delivery significantly predicted an earlier appearance of quiet sleep (p < 0.001). CONCLUSIONS: Appearance of quiet sleep after birth but not its length may be delayed in case of mild perinatal stress.

The effect of exposure to particulate matter during pregnancy on lower respiratory tract infection hospitalizations during first year of life.

BACKGROUND: Lower respiratory tract infections (LRTI) in early life, including pneumonia, bronchitis and bronchiolitis, can lead to decreased lung function, persistent lung damage and increased susceptibility to various respiratory diseases such as asthma. In-utero exposure to particulate matter (PM) during pregnancy may disrupt biological mechanisms that regulate fetal growth, maturation and development. We aimed to estimate the association between intrauterine exposure to PM of size < 2.5 µm in diameter (PM2.5) and incidence of LRTIs during the first year of life. METHODS: A retrospective population-based cohort study in a population of mothers and infants born in Soroka University Medical Center (SUMC) in the years 2004-2012. All infants < 1 year old that were hospitalized due to LRTIs were included. The main exposure assessment was based on a hybrid model incorporating daily satellite-based predictions at 1 km2 spatial resolution. Data from monitoring stations was used for imputation of main exposure and other pollutants. Levels of environmental exposures were assigned to subjects based on their residential addresses and averaged for each trimester. Analysis was conducted by a multivariable generalized estimating equation (GEE) Poisson regression. Data was analyzed separately for the two main ethnic groups in the region, Jewish and Arab-Bedouin. RESULTS: The study cohort included 57,331 deliveries that met the inclusion criteria. Overall, 1871 hospitalizations of infants < 1 year old due to pneumonia or bronchiolitis were documented. In a multivariable analysis, intrauterine exposure to high levels of PM2.5 (> 24 µg/m3) in the first and second trimesters was found to be adversely associated with LRTIs in the Arab-Bedouin population (1st trimester, RR = 1.31, CI 95% 1.08-1.60; 2nd trimester: RR = 1.34, CI 95% 1.09-1.66). CONCLUSION: Intrauterine exposure to high levels of PM2.5 is associated with a higher risk of hospitalizations due to lower respiratory tract infections in Arab-Bedouin infants.

Association of cerebral activity with MRI scans in infants with neonatal encephalopathy undergoing therapeutic hypothermia.

We aimed to correlate amplitude-integrated EEG (aEEG) in neonatal hypoxic ischemic encephalopathy (HIE) with early magnetic resonance imaging (MRI). In this retrospective study, 32 neonates over 35 weeks' gestation with moderate/severe HIE who were treated with hypothermia were included. Early MRI scans and daily aEEG background were categorized to mild/normal, moderate, and severely abnormal. Time to sleep cycling was noted on aEEG. Mantel-Haenszel test for trends was used to explore associations between aEEG and MRI and outcome. LOESS regression was used for exploring the association of cycling with MRI scores. MRI was normal/mildly abnormal in 20 (63%) infants; in 9 (28%), moderately abnormal; and in 3 (9%), severely abnormal. Twenty-seven (84%) infants s urvived. MRI severity score was significantly associated with aEEG background score on the third and fourth days of life (p < 0.01). An increase in the MRI severity score was noted if sleep cycling appeared after the fifth day of life.Conclusions: Depressed aEEG at the third and fourth days of life and appearance of cycling beyond the fifth day of life are associated with cerebral MRI abnormalities and may be associated with increased risk of abnormal outcome. What is known: • Since therapeutic hypothermia has been shown to change long-term outcome, amplitude-integrated EEG in infants with hypoxic ischemic neonatal encephalopathy soon after birth have a limited predictive power for long-term outcome in treated infants. • Brain MRI after therapeutic hypothermia in the above infants has a significant predictive value for long-term outcome What is new: • Background amplitude-integrated EEG activity depression at the age of 3 and 4 days and delay of appearance of cycling activity are associated with worse MRI scores and may be predictive of worse long-term outcome.

Neonatal Risk Factors for Colonization with Extended-Spectrum Beta-Lactamase-Producing Bacteria in the Neonatal Intensive Care Unit.

BACKGROUND: Extended-spectrum beta-lactamase (ESBL) production is the most common antimicrobial resistance mechanism in the neonatal intensive care unit (NICU), with colonization and blood stream infections being a major threat to this population. Since 2013, all NICU admissions at our facility were screened twice weekly for ESBL colonization. OBJECTIVES: To determine independent risk factors for colonization of infants with ESBL-producing bacteria in the NICU. METHODS: A retrospective case study of ESBL-colonized infants vs. controls (matched by date of birth and gestational age) was conducted in the NICU of Soroka University Medical Center, Israel, between 2013 and 2014. Epidemiological, laboratory, and clinical data were extracted from medical files. Univariable and multivariable analyses were used to assess associations between ESBL colonization and possible clinical risk factors. RESULTS: Of 639 admissions during the study period, 87 were found to be ESBL-colonized (case infants) and were matched to 87 controls. Five case infants became infected (5.7%) with ESBL strains. Klebsiella pneumoniae was the most common isolated bacteria. The mean time from admission to colonization was 15 days. Univariable analysis showed an association of male gender and highest Apgar score at 1 and 5 minutes with ESBL colonization (P < 0.05). Multivariable analysis yielded only a possible association of higher Apgar score at 1 and 5 minutes (hazard ratio [HR] 1.515, 95% confidence interval [95%CI] 0.993-2.314; HR 1.603, 95%CI 0.958-2.682, respectively) with ESBL colonization. CONCLUSIONS: Future studies should focus on maternal colonization and possible strategies for preventing vertical transmission of ESBL strains to high-risk neonates.

Diffusion Tensor Tractography of the Cerebellar Peduncles in Prematurely Born 7-Year-Old Children.

The objective of this study was to correlate neurodevelopmental outcome of preterm-born children and their perinatal clinical and imaging characteristics with diffusion magnetic resonance imaging (MRI) measures of the three cerebellar peduncles at age 7. Included in this prospective longitudinal study were 140 preterm-born children (<30 weeks gestation) who underwent neurodevelopmental assessment (IQ, motor, language, working memory) and diffusion-weighted imaging (DWI) at age 7 years. White matter tracts in the superior, middle, and inferior cerebellar peduncles were delineated using regions of interest drawn on T2-weighted images and fractional anisotropy (FA) maps. Diffusion measures (mean diffusivity (MD) and FA) and tract volumes were calculated. Linear regression was used to assess relationships with outcome. The severity of white matter injury in the neonatal period was associated with lower FA in the right superior cerebellar peduncle (SCP) and lower tract volumes of both SCPs and middle cerebellar peduncles (MCPs). In the MCP, higher IQ was associated with lower MD in the whole group and higher FA in right-handed children. In the SCP, lower motor scores were associated with higher MD and higher language scores were associated with higher FA. These associations remained significant in multivariable models. This study adds to the body of literature detailing the importance of cerebellar involvement in cognitive function related to reciprocal connections with supratentorial structures.

Comparison of early onset sepsis and community-acquired late onset sepsis in infants less than 3 months of age.

BACKGROUND: We compared demographic and clinical characteristics of early-onset sepsis (EOS) and community-acquired late onset sepsis (CA-LOS) in infants. METHODS: Our medical center is the sole hospital in southern-Israel, enabling incidence calculations. EOS (<7 days) and CA-LOS (7-90 days) episodes recorded between 2007 and 2013 were reviewed. Univariate and multivariate analyses were performed. RESULTS: 70 EOS and 114 CA-LOS episodes were recorded. The respective mean ± SD annual rates per 1,000 live-births were 0.66 ± 0.16 and 1.03 ± 0.23. Prematurity (42.9 % vs. 17.0 %), premature rupture of membranes (PROM; 22.9 % vs. 1.9 %), leukopenia (29.0 % vs. 11.6 %), thrombocytopenia (44.9 % vs. 14.3 %) and Streptococcus agalactiae infections (22.7 % vs. 8.1 %) were more common in EOS. Fever (25.4 % vs. 79.1 %) and Streptococcus pneumoniae infections (1.3 % vs. 12.9 %) were less common in EOS. In both groups, Gram-negative bacteria predominated (~60 %). Longer hospitalization duration (23.3 ± 25.1 vs. 10.3 ± 8.6 days) and higher case fatality rate (20.0 % vs. 5.3 %) were noted in EOS. Antibiotic resistance rates to empiric EOS and CA-LOS treatments were 0.0 % and 1.2 %, respectively. In multivariate analysis, adjusting for prematurity and ethnicity, PROM, central line, low Apgar-score, low birth-weight, ventilation support and non-vaginal delivery were risk factors for EOS. Normal temperature, thrombocytopenia and leukopenia characterized EOS. CONCLUSION: EOS and CA-LOS rates were low in Jewish compared with Bedouin infants. EOS was characterized by higher rates of perinatal risk factors, S. agalactiae infections, normal temperature, thrombocytopenia, leukopenia and mortality, while fever and S. pneumoniae infections were common in CA-LOS. Current initial antibiotic regimens seem adequate, considering the susceptibility patterns of the isolated pathogens.

[USING INFORMATION FROM COMPUTERIZED MEDICAL FILES TO DETERMINE THE RISK OF POOR OUTCOME IN EXTREMELY PRETERM INFANTS].

INTRODUCTION: During the last two decades preterm deliveries have been rising with increasing numbers of survivors at risk of abnormal outcomes. Characterization of risk factors for abnormal outcome is important for caregivers and patients' families. We hypothesized that it is possible to evaluate significant risk factors from computerized files early in life. OBJECTIVES: To evaluate data from computerized files that could help identify children born preterm at increased risk of abnormal outcomes without a neurodevelopmental exam. METHODS: This is a retrospective cohort study including children born at less than 29 weeks gestation and/or less than 1000 grams. The long term outcome was defined using data from the local child developmental center. Risk factors were retrieved from computerized files from birth until 3 years of age and assessed using univariate and multivariate analysis. RESULTS: A total of 74 children were included in the study; 30 with abnormal outcomes. The following parameters: Bedouin origin (p = 0.033), low 1 minute Apgar score (p = 0.044), late sepsis (p = 0.017), exposure to x-rays (p = 0.033), hospital based specialist visits (p = 0.017) and hospitalization (p = 0.035) were more common in the abnormal outcome group or increased its risk in univariate analysis. Bedouin origin (OR = 3.81-5.11), late sepsis (OR = 4.07-4.94) and hospital based specialist visits (OR = 4.67, 95% CI = 1.11-19.55) increased more than fourfold the risk of abnormal outcomes in multivariate analysis. CONCLUSIONS: This study has important implications as Bedouin origin and llate sepsis can be determined before discharge. Furthermore, follow-up of high risk children should be locally accessible. Prevention of late sepsis is of upmost importance, as well as awareness of specialists to the follow-up status of children born preterm.

The Association of Therapeutic Hypothermia With Seizure Burden in Neonates With Hypoxic-Ischemic Encephalopathy.

OBJECTIVES: To compare seizure burden between newborn infants treated with therapeutic hypothermia (TH) and those that were not and to compare the need for antiseizure medications (ASM) in a cohort of infants who were diagnosed with neonatal hypoxic-ischemic encephalopathy (HIE). METHODS: This was a retrospective cohort study on infants born after 35 weeks' gestation, diagnosed with moderate to severe HIE, monitored with amplitude-integrated electroencephalography (aEEG) and eligible for TH. Infants born before the implementation of TH in 2008 were compared with infants born thereafter who received TH. Seizure burden was assessed from aEEG as total time in minutes of seizures activity per hour of recording. Other clinical and demographic data were retrieved from a prospective local database of infants with HIE. RESULTS: Overall, 149 of 207 infants were included in the study: 112 exposed to TH and 37 not exposed. Cooled infants had a lower seizure burden overall (0.4 vs 2.3 min/h, P < 0.001) and were also less likely to be treated with ASM (74% vs 100%, P < 0.001). In multivariable regression models, not exposed to TH, having a depressed aEEG background, and having higher Apgar scores were associated with higher seizure burden (incidence rate ratio: 4.78 for noncooled infants, P < 0.001); also, not exposed to TH was associated with a higher likelihood of multidrug ASM (odds ratio: 4.83, P < 0.001). CONCLUSIONS: TH in infants with moderate to severe HIE is associated with significant reduction of seizure burden and ASM therapy.

Risk Factors for Perinatal Arterial Ischemic Stroke: A Machine Learning Approach.

BACKGROUND AND OBJECTIVES: Perinatal arterial ischemic stroke (PAIS) is a focal vascular brain injury presumed to occur between the fetal period and the first 28 days of life. It is the leading cause of hemiparetic cerebral palsy. Multiple maternal, intrapartum, delivery, and fetal factors have been associated with PAIS, but studies are limited by modest sample sizes and complex interactions between factors. Machine learning approaches use large and complex data sets to enable unbiased identification of clinical predictors but have not yet been applied to PAIS. We combined large PAIS data sets and used machine learning methods to identify clinical PAIS factors and compare this data-driven approach with previously described literature-driven clinical prediction models. METHODS: Common data elements from 3 registries with patients with PAIS, the Alberta Perinatal Stroke Project, Canadian Cerebral Palsy Registry, International Pediatric Stroke Study, and a longitudinal cohort of healthy controls (Alberta Pregnancy Outcomes and Nutrition Study), were used to identify potential predictors of PAIS. Inclusion criteria were term birth and idiopathic PAIS (absence of primary causative medical condition). Data including maternal/pregnancy, intrapartum, and neonatal factors were collected between January 2003 and March 2020. Common data elements were entered into a validated random forest machine learning pipeline to identify the highest predictive features and develop a predictive model. Univariable analyses were completed post hoc to assess the relationship between each predictor and outcome. RESULTS: A machine learning model was developed using data from 2,571 neonates, including 527 cases (20%) and 2,044 controls (80%). With a mean of 21 features selected, the random forest machine learning approach predicted the outcome with approximately 86.5% balanced accuracy. Factors that were selected a priori through literature-driven variable selection that were also identified as most important by the machine learning model were maternal age, recreational substance exposure, tobacco exposure, intrapartum maternal fever, and low Apgar score at 5 minutes. Additional variables identified through machine learning included in utero alcohol exposure, infertility, miscarriage, primigravida, meconium, spontaneous vaginal delivery, neonatal head circumference, and 1-minute Apgar score. Overall, the machine learning model performed better (area under the curve [AUC] 0.93) than the literature-driven model (AUC 0.73). DISCUSSION: Machine learning may be an alternative, unbiased method to identify clinical predictors associated with PAIS. Identification of previously suggested and novel clinical factors requires cautious interpretation but supports the multifactorial nature of PAIS pathophysiology. Our results suggest that identification of neonates at risk of PAIS is possible.

A prospective study of the patterns and dynamics of colonization with Candida spp. in very low birth weight neonates.

BACKGROUND: Knowledge of fungal colonization patterns in very low birth weight infants (VLBWI) admitted to the neonatal intensive care unit (NICU) is essential in understanding the process of fungal infections in neonates. We analyzed prospectively, during 2009-2010, the patterns and dynamics of fungal colonization in VLBWI, including timing, colonization sites, and species involved. METHODS: Weekly skin, oropharynx, and rectum/stool surveillance fungal cultures were collected from admission until discharge in VLBWI in the NICU. None received antifungal prophylaxis. RESULTS: Overall, 118 VLBWI provided 1723 samples; 34 (29%) had 104 positive samples at least once during the first 10 hospitalization weeks. Thirty-nine (33%) weighed < 1000 g; 68 were delivered by cesarean section. Candida albicans (57/104, 55%) and Candida parapsilosis (26/104, 25%) were the main fungi isolated. Eight (24%) VLBWI were colonized during the first week and 23 (68%) during the second week. No differences in colonization were recorded between cesarean section and vaginally delivered VLBWI. The colonization risk at least once during the first 10 weeks was 23% for skin, 14% for oropharynx, 27% for rectum/stool, and 38% for any anatomic site sampled. Persistent colonization was recorded in 5/34 (15%), while transient colonization was found in 14/34 (41%) VLBWI; 16/34 (47%) were discharged or died colonized with Candida spp. Candidemia was diagnosed in 4 (3%) VLBWI and previous/simultaneous colonization was found in 3/4. CONCLUSIONS: The cumulative risk of colonization, at any sampled site and at least once during follow-up, was high. Initial colonization occurred most often during the first 2 weeks of life. Colonization dynamics were characterized by various persistence, disappearance, and recolonization patterns. Candidemia was rare.

Infantile hypertrophic pyloric stenosis: maternal diabetes and perinatal exposure to non-macrolide antibiotics.

OBJECTIVE: Infant exposure to macrolide antibiotics is a risk factor for infantile hypertrophic pyloric stenosis (IHPS). The aim of the study was to establish whether perinatal exposure to non-macrolide antibiotics was a risk factor for IHPS. STUDY DESIGN: A retrospective matched case-control study was performed using a database including all children born at Soroka University Medical Centre between 2006 and 2018. Cases and controls were compared using Student T-test and multiple logistic regression. RESULT: Of 189 461 children in the database, 63 infants were diagnosed with IHPS and underwent pyloromyotomy. There was no association between non-macrolide antibiotic exposure and IHPS. Maternal diabetes (DM) had an adjusted odds ratio for infants developing IHPS of 4.53 (p = 0.004). CONCLUSION: The lack of association between exposure to non-macrolide antibiotics and IHPS suggests a quality unique to macrolides. An association between DM and IHPS may suggest elevated levels of IGF-1 have a role.

Intrapartum deceleration and acceleration areas are associated with neonatal encephalopathy.

OBJECTIVE: To investigate whether an association exists between deceleration and acceleration areas on continuous fetal cardiotocography (CTG) and neonatal encephalopathy (NE). METHODS: A single center, retrospective case-control study was conducted to compare CTG characteristics of low-risk pregnancies (35 weeks of gestation or more), complicated by moderate to severe NE with two matched controls for every case. Controls were matched by gestational age and cord blood pH. We analyzed the intrapartum CTG recordings by calculation of the deceleration and acceleration areas and the ratio between the two. RESULTS: During the period between 2013 and 2019, we identified 95 cases of low-risk pregnancies that were complicated by moderate to severe NE in our center. Thirty-three (34.7%) deliveries were excluded, mostly because of an insufficient duration of the CTG recordings. The remaining 62 cases were matched with 123 controls. We found that NE was significantly associated with an increased total deceleration area, a decreased total acceleration area, and a lower acceleration-to-deceleration ratio. CONCLUSIONS: NE was significantly associated with increased total deceleration area, decreased total acceleration area, and a lower acceleration-to-deceleration ratio, independent of cord blood pH. Development of a computerized real-time analysis of fetal heart rate tracings may contribute to making these measurements a more valid clinical tool.

Impact of an Online Program of Bubble Continuous Positive Airway Pressure Education in a Resource-Constrained Setting.

Background: Respiratory distress is a leading cause of preterm infant mortality in sub-Saharan Africa. Bubble continuous positive airway pressure (CPAP) is emerging as a potentially safe, cost-effective way of delivering noninvasive respiratory support in low-income and middle-income countries. However, without healthcare providers who are knowledgeable and skilled in the use of this technology, suboptimal neonatal care and related health disparities are likely to persist. Objective: We hypothesized that an Internet-based, blended curriculum on bubble CPAP for bedside providers in low-resource mother-baby units (MBUs) could be developed and implemented and lead to improvements in clinical knowledge, reasoning, and learner confidence in bubble CPAP. Methods: Clinical educators from Israel, Ghana, and the United States used the analysis, design, development, implementation, and evaluation (ADDIE) design framework to create an online curriculum for two MBUs in Kumasi, in the Ashanti Region of Ghana. Participants completed pre and post curriculum knowledge tests and completed surveys on their perspectives. Results: Fifty-four interdisciplinary health professionals from the MBUs participated in the curriculum. Median knowledge test scores improved from 64% (interquartile range [IQR] = 50-72%) to 81% (IQR = 71-89%) after participation in the curriculum (P < 0.001). Learners reported high levels of confidence with bubble CPAP after participating in the curriculum and evaluated the curricular components highly. Conclusion: An online curriculum was successfully implemented and led to changes in healthcare worker knowledge in bubble CPAP. This may be an effective way to deliver education to healthcare professionals in resource-constrained countries and warrants further study.

The impact of the pneumococcal conjugate vaccines on the incidence of community-acquired alveolar pneumonia in premature compared with in term-born infants.

BACKGROUND: Preterm-born children are prone to respiratory infections and complications during infancy and early childhood. In Israel, pneumococcal conjugated vaccines (PCVs) were introduced in 2009-2010, with high vaccination coverage. We assessed the impact of PCV implementation on community-acquired alveolar pneumonia (CAAP) in children < 2 years old born prematurely, in comparison with term born infants. METHODS: We conducted a prospective, active, population-based surveillance of children < 2 years old with radiologically-proven CAAP, visiting the only regional medical center. CAAP incidence in the pre-PCV and post-PCV eras were compared in early premature (29-32 weeks gestational age [WGA]), late premature (33-36 WGA) and term-born infants (>36 WGA). RESULTS: Of 214,947 births during the study period, 6'791 CAAP episodes were diagnosed; 211, 653 and 5,806 were in early premature, late premature and term infants, respectively. After PCV implementation, overall CAAP visits were reduced by 44% (95% CI 36-51): 60%, 21% and 45% among those born early preterm, late preterm and at term, respectively (statistically significant for children born early preterm and at term). For outpatients, the respective rate reductions were 79%, 40% and 65% (statistically significant for the children born at term). Importantly, the mean annual rates in the post-PCV period became similar in all 3 groups. The rate reductions among the hospitalized children were lower those that among the non-hospitalized children, with reductions of 56%, 16% and 33% for the three groups, respectively (statistically significant for early preterm and at term children). CONCLUSIONS: CAAP reduction trends after PCV implementation for preterm-born infants were similar to those for term-born infants. Whether this was because of similar direct PCV- protection, because of indirect (herd) protection or both, is unclear. Post-PCV implementation, the gaps in CAAP rates between infants born prematurely and at term were reduced.

Development and Validation of a Prediction Model for Perinatal Arterial Ischemic Stroke in Term Neonates.

Importance: Perinatal arterial ischemic stroke (PAIS) is a focal brain injury in term neonates that is identified postnatally but is presumed to occur near the time of birth. Many pregnancy, delivery, and fetal factors have been associated with PAIS, but early risk detection is lacking; thus, targeted treatment and prevention efforts are currently limited. Objective: To develop and validate a diagnostic risk prediction model that uses common clinical factors to predict the probability of PAIS in a term neonate. Design, Setting, and Participants: In this diagnostic study, a prediction model was developed using multivariable logistic regression with registry-based case data collected between January 2003, and March 2020, from the Alberta Perinatal Stroke Project, Canadian Cerebral Palsy Registry, International Pediatric Stroke Study, and Alberta Pregnancy Outcomes and Nutrition study. Criteria for inclusion were term birth and no underlying medical conditions associated with stroke diagnosis. Records with more than 20% missing data were excluded. Variable selection was based on peer-reviewed literature. Data were analyzed in September 2021. Exposures: Clinical pregnancy, delivery, and neonatal factors associated with PAIS as common data elements across the 4 registries. Main Outcomes and Measures: The primary outcome was the discriminative accuracy of the model predicting PAIS, measured by the concordance statistic (C statistic). Results: Of 2571 term neonates in the initial analysis (527 [20%] case and 2044 [80%] control individuals; gestational age range, 37-42 weeks), 1389 (54%) were male, with a greater proportion of males among cases compared with controls (318 [60%] vs 1071 [52%]). The final model was developed using 1924 neonates, including 321 cases (17%) and 1603 controls (83%), and 9 clinical factors associated with risk of PAIS in term neonates: maternal age, tobacco exposure, recreational drug exposure, preeclampsia, chorioamnionitis, intrapartum maternal fever, emergency cesarean delivery, low 5-minute Apgar score, and male sex. The model demonstrated good discrimination between cases and controls (C statistic, 0.73; 95% CI, 0.69-0.76) and good model fit (Hosmer-Lemeshow P = .20). Internal validation techniques yielded similar C statistics (0.73 [95% CI, 0.69-0.77] with bootstrap resampling, 10-fold cross-validated area under the curve, 0.72 [bootstrap bias-corrected 95% CI, 0.69-0.76]), as did a sensitivity analysis using cases and controls from Alberta, Canada, only (C statistic, 0.71; 95% CI, 0.65-0.77). Conclusions and Relevance: The findings suggest that clinical variables can be used to develop and internally validate a model to predict the risk of PAIS in term neonates, with good predictive performance and strong internal validity. Identifying neonates with a high probability of PAIS who could then be screened for early diagnosis and treatment may be associated with reductions in lifelong morbidity for affected individuals and their families.