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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

The effects of the COVID-19 pandemic on patients with lysosomal storage disorders in Israel.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is the causative agent of the current COVID-19 pandemic. Lysosomal storage disorders (LSD) comprise of 70 inherited inborn errors of metabolism. Affected individuals suffer from multi-systemic involvement with variable severity and rate of disease progression between different diseases. Some of the LSDs have established treatments, whether parenteral or oral therapies. The full impact of the COVID-19 pandemic together with the lockdown on the wellbeing and medical management of patients with rare diseases, such as LSDs, is widely unknown. Herein, we describe the effects of the COVID-19 pandemic and its associated mandatory home lockdown on patients with LSDs in Israel. RESULTS: We present a prospective multi-center questionnaire study including 48 LSD patients from four medical centers in Israel. The study objective was to assess the impact of the COVID-19 pandemic restrictions on individuals with LSDs in Israel, as reported by their caregivers. Secondary objectives were to assess the morbidity from SARS CoV-2 in LSD patients and the impact of changes in mood and behavior on compliance to treatment and to assess the relationship between changes in mood to changes in cognition and behavior. Thirty one of 38 patients (82%) who received any kind of regular treatment did not miss treatments. Among patients receiving enzyme replacement therapy (ERT) in the in-hospital setting, 5 patients (20%) experienced treatment disruptions. Four patients had tested positive for SARS-Cov-2 virus infection by PCR. Seven out of the 48 patients (14%) described mood changes with cognitive and motor deterioration during the home quarantine. CONCLUSIONS: We observed high rates of treatment adherence and low morbidity through the COVID-19 pandemic in patients with LSDs in Israel. LSDs patients can be a model for patients with complex chronic diseases requiring routine treatments and surveillance during a pandemic or other disruption of daily routine.

Clinical Application of Postmortem Magnetic Resonance Imaging in Neonates.

BACKGROUND: Recent reports advocate the use of MRI either as a substitute for postmortem examinations or for a more targeted autopsy. METHODS: A full-body postmortem MRI (pMRI) of infants was performed as early as possible after death, and findings were compared to clinical premortem diagnoses. RESULTS: Thirty-one infants were scanned during the study period. Median gestation at birth was 34 weeks (ranges: 24-43). In 3 (10%) cases, no new findings were detected. In 2 (6%), new minor findings not related to the cause of death were detected, and in 17 (55%), new minor findings related to the cause of death were detected. New major findings related to the cause of death were detected in 4 (13%) cases, and new major findings not related to the cause of death were detected in 5 (16%) cases. In 3 (10%), findings thought to alter the perceived cause of death were detected. Overall, in 23 (74%) cases, pMRI findings reinforced the clinical premortem diagnoses. CONCLUSIONS: pMRI is a culturally accepted alternative when autopsy is not performed and can either reinforce, refute, or add to premortem clinical diagnoses.

Effect of morphine on cerebral activity of extremely premature infants.

BACKGROUND: Morphine is widely used for sedation in premature infants and may have long-term effects on neurodevelopmental outcome. AIMS: To assess its effect on cerebral activity of extremely preterm infants. METHODS: Retrospective study in infants less than 28 weeks of gestational age (GA), treated with morphine and monitored with amplitude integrated EEG (aEEG), that were assessed at baseline and 6 consecutive 2 h periods. At each period, the background activity score and presence of cycling were determined. RESULTS: A total of 140 infants were included. Background aEEG activity score worsened in 40% of the infants by 6 h after morphine initiation and cycling, initially present in 70% of the infants, could be detected in only 10% after 10 h. On multivariable analysis, adjusted for baseline aEEG score and GA, the background activity decreased by 0.85 (95% confidence interval (CI): 0.74-0.97) immediately after morphine initiation, 0.72 (CI: 0.63-0.83) at 2 h later and on average by 0.64 (CI: 0.57-0.71) at each subsequent 2 h periods. The relative risk of cycling loss at 2 h and 4 h after morphine administration was 1.58 (CI: 1.15-2.16) and 3.37 (CI: 2.23-5.08), respectively. CONCLUSIONS: Continuous infusion of morphine in extremely preterm infants significantly depresses their cerebral activity soon after its commencement.

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.

Targeted and universal screen in term and preterm infants for congenital CMV infection.

Background: The aims of this study were to evaluate the incidence of congenital cytomegalovirus (CMV) in term and near-term infants who fail hearing screen (target screening), the incidence of congenital CMV infections in infants born before 33 weeks of gestation (universal screening) and the incidence of infants who need pharmacologic treatment for congenital CMV associated sensorineural hearing loss (SNHL).Methods: This was a retrospective cohort study that assessed two groups of infants born between 2014 and 2017. The first group consisted of infants born between 33 and 42 weeks gestation and the second group, of infants born before 33 weeks gestation. Targeted CMV screening was performed in the first group who either failed neonatal hearing screen or were growth retarded. Universal screen was performed in the second group of infants. CMV DNA was tested in urine samples using real time PCR soon after birth.Results: In the first group, 2078 infants were assessed, 19 (0.9%) were found to be CMV positive and in 9 (42%) valganciclovir treatment was initiated. In the second group, out of 549 urine samples/infants, none was positive for CMV DNA soon after birth.Conclusions: A joint strategy of targeted CMV screening in infants who fail hearing screen test with universal screen of premature infants can select infants at risk of hearing impairment due to congenital CMV soon after birth, allows for timely initiation of treatment and prevents dilemmas regarding congenital CMV diagnosis in infants who fail hearing screen in a later age until universal screen will be widely adopted.

Predictive Value of Early Amplitude Integrated EEG in Extremely Premature Infants.

Amplitude integrated EEG (aEEG) is increasingly utilized in preterm infants. The aim of the study was to evaluate whether semiquantitative visual assessment of aEEG background during the first 72 hours of life is associated with long-term outcome in a group of premature infants born less than 28 weeks' gestation. Infants were prospectively enrolled and monitored in the first 72 hours after birth. aEEG was classified daily according to background activity, appearance of cyclical activity and presence of seizures activity. Log-rank and multivariable cox analysis were used to explore associations of background aEEG activity with short and long-term outcome. Overall, 51 infants were enrolled into the study. Depressed aEEG background on the third day of life was associated with poor outcome (P = .028). Similarly, absence of cycling on the third day of life was associated with death or poor outcome (P = .004 and .012, respectively). In different multivariable models adjusted for gestational age, severe intraventricular hemorrhage or use of sedative medication, neither background nor cycling activities were associated with outcome. Depressed aEEG background and absence of aEEG cycling on the third day of life are associated with poor outcome in univariable analysis. Although continuous aEEG monitoring of premature infants can provide real-time assessment of cerebral function, its use as a predictive tool for long-term outcome using visual analysis requires caution as its predictive power is not greater than that of gestational age or intraventricular hemorrhage.

Health Care Resource Utilization of Late Premature Versus Term Infants With Bronchiolitis.

It is controversial whether it is cost-beneficial for late preterm infants to receive respiratory syncytial virus prophylaxis. This study compares community and hospital health care resource utilization (HCRU) of late premature infants (33-36 weeks gestational age) with term infants (>36 weeks gestational age) hospitalized with bronchiolitis. This was a retrospective, population-based, observational study spanning a 9-year period (2004-2012). HCRU data were obtained from the Health Maintenance Organization "Clalit" and included duration of hospitalization, physician visits, laboratory tests, and treatments. Compared with term infants, late preterm infants had significantly longer duration of hospitalization and higher admission rates to pediatric intensive care unit. They also had higher rates of mean outpatients clinic visits, total outpatient clinic and specialist visits, blood chemistry, and virology testing. HCRU of term infants with bronchiolitis was also substantial, indicating that they also can greatly benefit from respiratory syncytial virus prophylaxis. These findings can guide stakeholders in decisions concerning the prevention of bronchiolitis and will be useful in performing further cost-benefit analysis.

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.