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.

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.

Maternal Postpartum Emotional Distress and Preterm Social Withdrawal in the Bedouin Culture.

This study aimed to test a serial mediation model proposing that prematurity would be related to changes in maternal emotional distress, which in turn would be related to the mother-child (M-C) interaction, which would ultimately be related to infant social withdrawal. Bedouin mothers and their preterm (n = 48) and full-term (n = 57) infants participated in this study. Mothers' mean age was 27.67 years. In addition, 39.4% of the mothers were primiparas and 60.6% were multiparas. Infants and their mothers were recruited shortly after birth (T1) in the maternity ward or Neonatal Intensive Care Unit (NICU) at Soroka Medical Center and were followed up at ages 6 months (T2) and 12 months (T3). Findings indicated that HIGHER levels of maternal emotional distress during the second half of the first year postpartum and LOWER levels of mother-child interaction, were associated with HIGHER levels of infant social withdrawal at T3. Furthermore, the overall indirect effect suggested that HIGHER levels of maternal nonhostility was a main variable mediating the link between prematurity and LOW levels of infant social withdrawal. Our findings provide evidence that changes in maternal emotional distress during the first year are related to lower infant social withdrawal. Moreover, mothers of premature infants showed higher levels of nonhostility when interacting with their premature infants. These findings highlight the importance of gaining a better understanding of maternal behaviors. Specifically, our study provides important information for researchers and clinicians on a possible mechanism leading to early socioemotional difficulties of premature infants.

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.

Prematurity, maternal emotional distress, and infant social responsiveness among Arab-Bedouin families: The role of social support as a resilience factor.

This study investigated predictors of early infant social development and the role of social support as a resilience factor among Arab-Bedouin families. We propose a mediation model in which social support will be related to maternal postpartum emotional distress (PPED), which in turn will be related to infant social responsiveness. One hundred five Arab-Bedouin mothers (age range = 17-44 years) and their preterm (n = 48) and full-term (n = 57) infants were recruited shortly after birth and were followed up at age 12 months. Findings demonstrate that, among the preterm group, higher levels of social support predicted lower levels of maternal PPED, and this, in turn, predicted higher levels of infant social responsiveness.

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.

Maternal Smoking during Pregnancy and the Risk for Childhood Infectious Diseases in the Offspring: A Population-Based Cohort Study.

OBJECTIVE: Infectious diseases account for up to 43% of childhood hospitalizations. Given the magnitude of infection-related hospitalizations, we aimed to evaluate the effect of maternal smoking during pregnancy on the risk for long-term childhood infectious morbidity. STUDY DESIGN: This is a population-based cohort analysis comparing the long-term risk for infectious diseases, in children born to mothers who smoked during pregnancy versus those who did not. Infectious diseases were predefined based on International Classification of Diseases, Ninth Revision codes. Deliveries occurred between the years 1991 and 2014. RESULTS: A total of 246,854 newborns met the inclusion criteria; 2,986 (1.2%) were born to mothers who smoked during pregnancy. Offspring of smokers had significantly higher risk for several infectious diseases during childhood (upper respiratory tract, otitis, viral infections, and bronchitis) as well as increased risk for total infection-related hospitalizations (odds ratio = 1.5, 95% confidence interval [CI]: 1.3-1.7; p = 0.001). Cumulative incidence of infection-related hospitalizations was significantly higher in offspring of smokers (log-rank test, p = 0.001). Controlling for maternal age, diabetes, hypertensive disorders, and gestational age at index delivery, smoking remained an independent risk factor for infectious diseases during childhood (adjusted hazard ratio = 1.5, 95% CI: 1.3-1.6; p = 0.001). CONCLUSION: Intrauterine exposure to maternal smoking may create an environment leading to an increased future risk for long-term pediatric infectious morbidity of the offspring.

Prematurity and Maladaptive Mealtime Dynamics: the Roles of Maternal Emotional Distress, Eating-Related Cognitions, and Mind-Mindedness.

Premature birth and maternal emotional distress constitute risk factors for feeding disorders. This study examined the roles of maternal cognitions in the link between prematurity, emotional distress and mother-infant maladaptive mealtime dynamics in a sample of 134 families (70 preterm, low medical risk; 64 full-term) followed longitudinally. Specifically, maternal cognitions related to eating and health (perception of child vulnerability and concerns about child's eating) and understanding of mental states (interactional mind-mindedness) were considered. A multiple-mediators model was tested, controlling for infants' weight and breastfeeding history. Although prematurity did not directly predict mealtime dynamics, multiple-mediation analyses revealed indirect pathways: mothers of preterm newborns reported higher emotional distress, which subsequently predicted perception of child vulnerability and concerns about child's eating at 6-months; perception of child vulnerability predicted more conflictual mealtime dynamics, whereas concern about child's eating predicted less reciprocal mealtime dynamics at 12-months. Mind-mindedness at 6-months predicted more reciprocal and less conflictual mealtime dynamics but did not act as a mediator. Implications for understanding pathways from prematurity to feeding disorders are discussed.

Neonatal Risk, Maternal Sensitive-Responsiveness and Infants' Joint Attention: Moderation by Stressful Contexts.

Neonatal risk factors have been associated with atypical development in various areas of social communication, including joint attention (JA), but little is known about factors in the early caregiving environment that can modify the negative implications of neonatal risk. The present study examines the links between neonatal risk and infants' JA, while considering the mediating role of maternal sensitive-responsiveness and the moderating roles of stressful contexts. One hundred and eighty-two families with infants (50% female) born in a wide range of gestational ages and birthweights participated in the study. Neonatal risk was assessed shortly after birth using three indicators: birthweight, gestational age, and degree of medical risk. At age 6 months, maternal sensitive-responsiveness to infants' foci of attention was rated and maternal anxiety and household chaos were measured. Infants' JA behaviors were assessed at age 12 months. A moderated-mediation model revealed that maternal anxiety symptoms and household chaos moderated the links between neonatal risk, maternal sensitive-responsiveness, and infants' responding to JA. Specifically, neonatal risk was related to less maternal sensitive-responsiveness only when maternal anxiety symptoms were above average levels, but not when anxiety symptoms were low. Moreover, maternal sensitive-responsiveness was positively related to infants' responding to JA behaviors when household chaos was low but not when it was high. These findings highlight the complex nature of the links between infants' early biological risk and caregiving environments in the development of social communication skills.

[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 Caregiving Environment and Developmental Outcomes of Preterm Infants: Diathesis Stress or Differential Susceptibility Effects?

The interactions between premature birth and the caregiving environment on infants' cognitive and social functioning were examined. Participants were 150 infants (83 preterm, 67 full-term) and their parents. When infants were 6 months old, parents reported on their levels of emotional distress, and triadic family interactions were filmed and coded. At 12 months of age, the infants' cognitive and social functioning was assessed. Prematurity moderated the effects of maternal (but not paternal) emotional distress and triadic interactions on infants' cognitive and social outcomes. Whereas for cognitive functioning the interactions were consistent with a diathesis-stress approach, for social functioning the interactions were consistent with a differential susceptibility approach. The differential effects of the caregiving environment between groups and outcomes are discussed.

Persistent pulmonary hypertension of the newborn associated with severe congenital anemia of various etiologies.

Among the many associated features of persistent pulmonary hypertension of the neonate (PPHN), severe congenital anemia has been described only occasionally and is not included in the list of conditions that may cause PPHN in the neonate. We describe the clinical course of a group of 12 full-term neonates with PPHN and congenital anemia due to congenital dyserythropoietic anemia (7/12), α thalasemia (1/12), Diamond-Blackfan (1/12), and epsilon gamma delta beta thalassemia (3/12). The association of congenital anemia and PPHN is more common than previously thought; it can exist with various etiologies and severity of anemia. Congenital anemia has not been described until now as a cause or risk factor for PPHN; it should be considered as such alone or in combination with other known causes to be recognized early and treated appropriately to improve outcome. In families with known cases of congenital anemia due to the above-mentioned diagnosis, closer prenatal follow-up should be offered to anticipate possible fetal distress and/or fetal anemia and PPHN after birth.

Understanding utilization of outpatient clinics for children with special health care needs in southern Israel.

To understand the pattern of utilization of ambulatory care by parents of children with special health care needs (CSHCN) and to explore parental challenges in coping with health maintenance of their infants after discharge from a neonatal intensive care unit (NICU). CSHCN require frequent utilization of outpatient ambulatory clinics especially in their first years of life. Multiple barriers are faced by families in disadvantaged populations which might affect adherence to medical referrals. Our study attempts to go beyond quantitative assessment of adherence rates, and capture the influence of parental agency as a critical factor ensuring optimal utilization of healthcare for CSHCN. A prospective, mixed-methods, cohort study followed 158 Jewish and Bedouin-Arab infants in the first year post discharge from NICU in southern Israel. Rates of utilization of ambulatory clinics were obtained from medical records, and quantitative assessment of factors affecting it was based on structured interviews with parents at baseline. Qualitative analysis was based on home visits or telephone in-depth interviews conducted about 1 year post-discharge, to obtain a rich, multilayered, experiential perspectives and explained perceptions by parents. Adherence to post-discharge referrals was generally good, but environmental, cultural, and financial obstacles to healthcare, magnified by communication barriers, forced parents with limited resources to make difficult choices affecting utilization of healthcare services. Improving concordance between primary caregivers and health care providers is crucial, and further development of supportive healthcare for CSHCN in concordance with parental limitations and preferences is needed.

Neonatal seizure recognition--comparative study of continuous-amplitude integrated EEG versus short conventional EEG recordings.

OBJECTIVES: This study aims to detect seizures by amplitude-integrated electroencephalography (EEG) (aEEG) as compared with conventional EEG (cEEG) by clinicians with different levels of expertise. METHODS: Simultaneous 10 min aEEG/cEEG recordings were time-locked and assessed for seizure activity. aEEG was assessed by a neonatologist, a fellow and a medical student and cEEG by two child neurologists and a neonatologist. RESULTS: A total of 265 paired epochs from 38 simultaneous recording were assessed. Forty-one seizure episodes were diagnosed in 31 epochs in the cEEG recordings of 10 infants. Sensitivity and specificity ranged from 68% to 84% and from 71% to 84%, respectively, per detection of epochs with seizures and from 71% to 84% and from 36% to 96% per detection of individual seizures. No agreement was found between the observations of the student, and those of the fellow or neonatologist. Substantial agreement was found between the fellow and neonatologist. Before cEEG was commenced, seizures were detected by aEEG in 22 infants. CONCLUSIONS: aEEG has high sensitivity and specificity in the hands of experienced users. Inexperienced new users may have a high rate of misdiagnosed seizures. Early recording of high-risk infants can help in the early diagnosis and treatment of seizures. SIGNIFICANCE: Diagnosis and treatment of seizures in aEEG should be carried out by experienced users and should be supplemented with cEEG when available.

Oral insulin supplementation in paediatric short bowel disease: a pilot observational study.

BACKGROUND AND AIM: Insulin is present in human milk, and oral insulin supplementation causes a dramatic adaptive gut growth in a rat model of short bowel syndrome (SBS). We conducted an open-label pilot observational study to examine whether oral insulin supplementation to paediatric patients with SBS decreases the need for parenteral nutrition (PN). METHODS: Between April 2004 and March 2006, 10 premature infants and children were recruited from 8 paediatric gastroenterology centres in Israel, Croatia, and Germany. Enrolled subjects received 1 unit of insulin (Actrapid, Novonordisk, Denmark)/kg body weight per dose x 4/day (every 6 hours) for 28 days. We monitored glucose blood levels, weight, enteral and parenteral intake of calories, carbohydrates, and lipids. In addition, blood levels of albumin, ALT, AST, GGT, ALP, total cholesterol, triglycerides, and anti-insulin antibodies were recorded. RESULTS: On average, enteral intake increased from 45.6% +/- 30.6% to 58.9% +/- 28.2% (not statistically significant), and ALT blood levels decreased from 194 +/- 128 U to 136 +/- 79 U (not statistically significant). Two (2/10) infants were weaned off PN. None of the children developed insulin antibodies. CONCLUSIONS: Oral insulin supplementation in paediatric SBS is not associated with short-term side effects. Although clinical improvement was observed in a subset of children, whether these effects are due to insulin administration is uncertain. The efficacy of oral insulin remains to be determined in a double-blind manner using a preparation that is resistant to degradation in the stomach.

The additional dose to radiosensitive organs caused by using under-collimated X-ray beams in neonatal intensive care radiography.

Radiographic technique and exposure parameters were recorded in five Israeli Neonatal Intensive Care Units for chest, abdomen and both chest and abdomen X-ray examinations. Equivalent dose and effective dose values were calculated according to actual examination field size borders and proper technique field size recommendations using PCXMC, a PC-based Monte Carlo program. Exposure of larger than required body areas resulted in an increase of the organ doses by factors of up to 162 (testes), 162 (thyroid) and 8 (thyroid) for chest, abdomen and both chest and abdomen examinations, respectively. These exposures increased the average effective dose by factors of 2.0, 1.9 and 1.3 for the chest, abdomen and both chest and abdomen examinations, respectively. Differences in exposure parameters were found between the different neonatal intensive care units-tube voltage, current-time product and focal to skin distance differences up to 13, 44 and 22%, respectively. Reduction of at least 50% of neonate exposure is feasible and can be implemented using existing methodology without any additional costs.