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Background and Objectives: Perinatal hypoxic-ischemic brain injury is a leading cause of term-born cerebral palsy, the most common lifelong physical disability. Diagnosis is commonly made in the neonatal period by the combination of neonatal encephalopathy (NE) and typical neuroimaging findings. However, children without a history of neonatal encephalopathy may present later in childhood with motor disability and neuroimaging findings consistent with perinatal hypoxic-ischemic injury. We sought to determine the prevalence of such presentations using the retrospective viewpoint of a large multiregional cerebral palsy registry., Methods: Patient cases were extracted from the Canadian Cerebral Palsy Registry with gestational age >36 weeks, an MRI pattern consistent with hypoxic-ischemic injury (HII, acute total, partial prolonged, or combined), and an absence of postnatal cause for HII. Documentation of NE was noted. Maternal-fetal risk factors, labor and delivery, neonatal course, and clinical outcome were extracted. Comparisons were performed using χ 2 tests and multivariable logistic regression with multiple imputation. Propensity scores were used to assess for bias., Results: Of the 170 children with MRI findings typical for HII, 140 (82.4%, 95% confidence interval [CI] 75.7%-87.7%) had documented NE and 29 (17.0%, 95% CI 11.7%-23.6%) did not. The group without NE had more abnormalities of amniotic fluid volume (odds ratio [OR] 15.8, 95% CI 1.2-835), had fetal growth restriction (OR 4.7, 95% CI 1.0-19.9), had less resuscitation (OR 0.03, 95% CI 0.007-0.08), had higher 5-minute Apgar scores (OR 2.2, 95% CI 1.6-3.0), were less likely to have neonatal seizures (OR 0.004, 95% CI 0.00009-0.03), and did not receive therapeutic hypothermia. MRI was performed at a median 1.1 months (interquartile range [IQR] 0.67-12.8 months) for those with NE and 12.2 months (IQR 6.6-25.9) for those without ( p = 0.011). Patterns of injury on MRI were seen in similar proportions. Hemiplegia was more common in those without documented NE (OR 5.1, 95% CI 1.5-16.1); rates of preserved ambulatory function were similar., Discussion: Approximately one-sixth of term-born children with an eventual diagnosis of cerebral palsy and MRI findings consistent with perinatal hypoxic-ischemic brain injury do not have documented neonatal encephalopathy, which was associated with abnormalities of fetal growth and amniotic fluid volume, and a less complex neonatal course. Long-term outcomes seem comparable with their peers with encephalopathy. The absence of documented neonatal encephalopathy does not exclude perinatal hypoxic-ischemic injury, which may have occurred antenatally and must be carefully evaluated with MRI.

Citrin deficiency is an autosomal recessive metabolic liver disease caused by mutations in the SLC25A13 gene. The disease typically presents with cholestasis, elevated liver enzymes, hyperammonemia, hypercitrullinemia, and fatty liver in young infants, resulting in a phenotype known as "neonatal intrahepatic cholestasis caused by citrin deficiency" (NICCD). The diagnosis relies on clinical manifestation, biochemical evidence of hypercitrullinemia, and identifying mutations in the SLC25A13 gene. Several common mutations have been found in patients of East Asian background. The mainstay treatment is nutritional therapy in early infancy utilizing a lactose-free and medium-chain triglyceride formula. This approach leads to the majority of patients recovering liver function by 1 year of age. Some patients may remain asymptomatic or undiagnosed, but a small proportion of cases can progress to cirrhosis and liver failure, necessitating liver transplantation. Recently, advancements in newborn screening methods have improved the age of diagnosis. Early diagnosis and timely management improve patient outcomes. Further studies are needed to elucidate the long-term follow-up of NICCD patients into adolescence and adulthood., (© 2023 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: This study assessed the association between MT and weight gain among preterm infants hospitalized in Neonatal Intensive Care Units., Methods: Data collected during the international, randomized, Longitudinal Study of Music Therapy's Effectiveness for Premature Infants and their Caregivers (LongSTEP) study were compared between the MT group and the standard care (SC) group. Weights were recorded at birth, enrollment, and discharge. Weight percentiles, Z-scores, weight gain velocity, and extrauterine growth restriction (EUGR) were calculated., Results: Among 201 preterm infants included, no significant differences in weight parameters (weight, weight percentiles, weight Z-scores; all p ≥ 0.23) were found between the MT group (n = 104) and the SC (n = 97) group at birth, enrollment, or discharge. No statistical differences in EUGR represented by change in Z-scores from birth to discharge were recorded between MT and SC (0.8 vs. 0.7). Among perinatal parameters, younger gestational age (p = 0.005) and male sex (p = 0.012) were associated with increased risk of EUGR at discharge. Antenatal steroid treatment, systemic infection, bronchopulmonary dysplasia, neurological morbidities, retinopathy of prematurity, necrotizing enterocolitis, parental factors (amount of skin-to-skin care, bonding, anxiety, and depression questionnaire scores), and type of enteral nutrition did not significantly influence weight gain parameters (all p > 0.05)., Conclusions: In the LongSTEP study, MT for preterm infants and families was not associated with better weight parameters compared to the SC group. The degree of prematurity remains the main risk factor for unfavorable weight parameters., (© 2023 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: To examine the association between birth weight percentile and severe infant outcomes according to gestational age category., Methods: We conducted a population-based retrospective cohort study using publicly available U.S. birth certificate data linked to infant death data from 2017 to 2019. Maternal-neonate pairs of singleton live births between 28 0/7 and 41 6/7 weeks of gestation (vaginal or cesarean delivery) were evaluated. We excluded infants with major fetal anomalies, chromosomal disorders, missing data, and birth weight outliers. The primary outcome was infant mortality within 1 year of life. Neonates were divided into eight sex-specific birth weight percentile categories: less than the 3rd, 3rd-less than the 10th, 10th-less than the 25th, 25th-to less than the 49th, 50th-less than the 75th, 75th-to less than the 90th, 90th-less than the 97th, and 97th or higher., Results: There were 10,459,388 births between 28 and 41 weeks of gestation: 69,793 (0.7%) at 28-31 weeks, 88,673 (0.8%) at 32-33 weeks, 635,904 (6.1%) at 34-36 weeks, 2,763,110 (26.4%) at 37-38 weeks, 6,269,894 (59.9%) at 39-40 weeks, and 632,014 (6.0%) at 41 weeks. Infant mortality during the first year of life significantly increased at higher and lower birth weight percentiles at 28-36 weeks of gestation, with the lowest risk observed at the 50th-less than the 75th percentile. The highest mortality rates were 13.6% at less than the 3rd percentile and 8.4% at the 97th percentile or higher at 28-31 weeks of gestation; the second-highest mortality rates were 7.7% at less than the 3rd percentile and 3.1% at the 97th percentile or higher at 32-33 weeks of gestation. At 34-36 weeks of gestation, the highest and second-highest mortality rates were 3.4% at less than the 3rd percentile and 1.4% at the 3rd-10th percentile. At 37-41 weeks of gestation, infant mortality was associated with lower birth weight percentile, but higher birth weight percentiles were not significantly associated with increased mortality., Conclusion: We found different patterns in the association between birth weight percentile and infant mortality depending on gestational age category., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Infants born with esophageal atresia and tracheoesophageal fistula, a complex congenital malformation occurring in 1/2500-4000 live births, may suffer threats to their cardiac, respiratory, and digestive health in addition to anomalies that may exist in the genitourinary and musculoskeletal systems. Optimal care for these patients throughout their lives is best achieved through a coordinated, multidisciplinary approach that our health care system is not always well-equipped to provide. This review, though not exhaustive, highlights the components of care that pertain to initial surgical reconstruction and subsequent diagnosis and management of the complications that are most frequently encountered. Authors from among the many specialties involved in the care of these patients summarize the current best practice with attention to the most recent advances. Assessment and improvement of quality of life and transition to adult specialists as children grow to adulthood is also reviewed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Amplitude integrated electroencephalography (aEEG) is a mainstay of care in neonatal ICUs; however, knowledge gaps exist in relation to its accuracy for identifying seizures in older children. We aimed to review the diagnostic accuracy of existing neonatal seizure detection criteria for seizure detection in older children in hospital., Design: Retrospective study., Setting: PICU/Neurophysiology Department in Dublin., Patients: One hundred twenty patients (2 mo to 16 yr old) were chosen from a database of formal 10-20 system, 21-lead electroencephalography recordings (2012-2020), comprising 30 studies with seizures, 90 without., Interventions: None., Measurements and Main Results: Electroencephalography studies containing electrographic seizures (ESzs) were annotated to describe number, duration, distribution, and spread. Two-channel aEEG (using leads C3-P3, C4-P4) recordings were generated and independently reviewed by a professional specialist in clinical neurophysiology blinded to outcome and without reference to the raw electroencephalography trace. Logistic regression was used to identify factors associated with correct seizure identification on aEEG. Median patient age was 6.1 years. Abnormal recordings featured 123 seizures. Status epilepticus (SE) was evident by electroencephalography in 10 cases. Using neonatal criteria, aEEG had a sensitivity of 70% and negative predictive value of 90% for identifying any ESz. Accurate detection of individual seizures was diminished when seizures were very short or occurred during waking. Sensitivity for individual seizures was 81% when seizures less than 1 minute were excluded. aEEG correctly identified SE in 70% of the 10 cases, although ESz were confirmed to be present in 80% of this subpopulation., Conclusions: aEEG criteria for neonatal seizure identification can be applied with caution to older children and should be supplemented by formal electroencephalography. Seizure identification is better for longer seizures and those arising from sleep. SE is not always recognized by aEEG among older children., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Rationale: Congenital pulmonary airway malformation (CPAM) is a rare congenital dysplastic malformation and accounts for 25% of congenital lung lesions. Commonly, it is diagnosed prenatally in ultrasound. The CPAM volume ratio (CVR) is a well-recognized predictor of fetal prognosis, and when the CVR is >1.6 cm2, the fetus is very likely to develop hydrops and even intrauterine deaths. However, the association of CVR with a wide range of complications and neonatal prognosis is unclear., Patient Concerns: Cystic lesions in the right thorax of the fetus detected by ultrasound at 19 weeks of gestation, with a CVR of 0.88 cm2. The CVR grew progressively with increasing gestational weeks, reaching a maximum of 5.2 cm2 at 35 gestational weeks. However, there were no complications with the fetus other than polyhydramnios., Diagnosis: Imaging and pathological findings confirmed the diagnosis of CPAM., Interventions: During pregnancy, a multidisciplinary team was involved in the management and the prenatal visits increased to weekly from 31 weeks of gestation. During the cesarean section, neonatologists and pediatric surgeons were present for timely evaluation of newborns. The neonate was admitted to the neonatal intensive care unit for monitoring immediately after birth and underwent thoracoscopic right lower lobectomy at 57th days old., Outcomes: The neonate recovered without any respiratory symptoms and no abnormality on chest computed tomography (CT) at the 3-month postoperative follow-up., Lessons: During pregnancy, in addition to monitoring CVR, a multidisciplinary team should join in the management of CPAM patients. And as for the fetus with increased CVR, a closely monitoring after birth is necessary even if the general condition of the pregnancy is well. In particular, timely intervention should be made at the onset of respiratory symptoms., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study aimed to investigate the risk factors associated with neonatal hypoglycemia and its correlation with blood glucose control in patients with gestational diabetes mellitus (GDM). This study was a retrospective study. 880 pregnant women with GDM and their newborns were hospitalized from January 2018 to December 2022 in our hospital. The clinical information of GDM pregnant women and their newborns were reviewed and the hemoglobin A1c (HbA1c) values measured within 1 week before delivery were collected. According to the occurrence of neonatal hypoglycemia, which was divided into the control and observation groups. Logistic regression model was used to estimate the potential factors associated with neonatal hypoglycemia. The association between HbA1c of pregnant women before delivery and abnormal glucose metabolism in newborns was examined using spearman correlation analysis. A total of 104 cases of hypoglycemia occurred in neonates delivered by 880 GDM women and the incidence of neonatal hypoglycemia was 11.82%. There were significant differences in pre-pregnancy overweight or obesity, delivery mode, maternal blood sugar control effect and neonatal feeding standard between the 2 groups of GDM women (P < .05). Pre-pregnancy overweight or obesity, poor blood sugar control in GDM women, and improper neonatal feeding were risk factors for neonatal hypoglycemia. The results of logistic regression analysis showed that abnormal glucose metabolism in newborn (odds ratio [OR]: 2.43, 95% confidence interval [CI]: 1.12-4.73) and neonatal hypoglycemia (OR: 3.04, 95% CI: 1.33-5.79) were a risk factor. We also conducted the logistic analysis to evaluate the correlation between HbA1c before delivery and abnormal glucose metabolism in newborns of pregnant women with GDM through adjusting some potential factors. The results were still significant in the abnormal glucose metabolism in newborn (OR: 2.84, 95% CI: 1.23-6.63) and neonatal hypoglycemia (OR: 3.64, 95% CI: 1.46-8.18). Overweight or obesity of GDM parturient before pregnancy, poor blood glucose control of GDM parturient and improper feeding of newborns are all risk factors for neonatal hypoglycemia. HbA1c before delivery has a certain predictive value for abnormal glucose metabolism in newborns., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Hematoma clearance has been a proposed therapeutic strategy for hemorrhagic stroke. This study investigated the impact of CX3CR1 (CX3C chemokine receptor 1) activation mediated by r-FKN (recombinant fractalkine) on hematoma resolution, neuroinflammation, and the underlying mechanisms involving AMPK (AMP-activated protein kinase)/PPARγ (peroxisome proliferator-activated receptor gamma) pathway after experimental germinal matrix hemorrhage (GMH)., Methods: A total of 313 postnatal day 7 Sprague Dawley rat pups were used. GMH was induced using bacterial collagenase by a stereotactically guided infusion. r-FKN was administered intranasally at 1, 25, and 49 hours after GMH for short-term neurological evaluation. Long-term neurobehavioral tests (water maze, rotarod, and foot-fault test) were performed 24 to 28 days after GMH with the treatment of r-FKN once daily for 7 days. To elucidate the underlying mechanism, CX3CR1 CRISPR, or selective CX3CR1 inhibitor AZD8797, was administered intracerebroventricularly 24 hours preinduction of GMH. Selective inhibition of AMPK/PPARγ signaling in microglia via intracerebroventricularly delivery of liposome-encapsulated specific AMPK (Lipo-Dorsomorphin), PPARγ (Lipo-GW9662) inhibitor. Western blot, Immunofluorescence staining, Nissl staining, Hemoglobin assay, and ELISA assay were performed., Results: The brain expression of FKN and CX3CR1 were elevated after GMH. FKN was expressed on both neurons and microglia, whereas CX3CR1 was mainly expressed on microglia after GMH. Intranasal administration of r-FKN improved the short- and long-term neurobehavioral deficits and promoted M2 microglia polarization, thereby attenuating neuroinflammation and enhancing hematoma clearance, which was accompanied by an increased ratio of p-AMPK (phosphorylation of AMPK)/AMPK, Nrf2 (nuclear factor erythroid 2-related factor 2), PPARγ, CD36 (cluster of differentiation 36), CD163 (hemoglobin scavenger receptor), CD206 (the mannose receptor), and IL (interleukin)-10 expression, and decreased CD68 (cluster of differentiation 68), IL-1β, and TNF (tumor necrosis factor) α expression. The administration of CX3CR1 CRISPR or CX3CR1 inhibitor (AZD8797) abolished the protective effect of FKN. Furthermore, selective inhibition of microglial AMPK/PPARγ signaling abrogated the anti-inflammation effects of r-FKN after GMH., Conclusions: CX3CR1 activation by r-FKN promoted hematoma resolution, attenuated neuroinflammation, and neurological deficits partially through the AMPK/PPARγ signaling pathway, which promoted M1/M2 microglial polarization. Activating CX3CR1 by r-FKN may provide a promising therapeutic approach for treating patients with GMH., Competing Interests: Disclosures None.

While neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe neonatal thrombocytopenia good clinical predictors are lacking. We analyzed cases of neonatal thrombocytopenia in Schneider Children's Medical Center of Israel to pinpoint qualifiers of NAIT (NAIT+) in comparison to non-NAIT (NAIT-) thrombocytopenia. Patient and maternal data were retrospectively collected on all thrombocytopenic newborns undergoing a workup for NAIT in our tertiary center between 2001 and 2016. Among 26 thrombocytopenic neonates, the mean nadir in NAIT+ patients (25×10 9 /L) was significantly lower than NAIT- patients (64×10 9 /L) ( P <0.001). 61.5% of NAIT+ infants required treatment compared with 23% of non-NAIT ( P =0.015). NAIT+ patients also required more therapeutic modalities than infants with NAIT- thrombocytopenia. Human platelet antigen (HPA)-1a and HPA-5b alloantibodies most frequently caused NAIT. In summary, thrombocytopenia in NAIT+ was significantly more severe compared with NAIT- and more likely to require treatment. In addition, despite the varied ethnic population in Israel, the HPA alloantibodies found in our population were most similar to those common in Western countries. In the absence of rigorous prenatal screening options, we suggest platelet counts below 40 to 50×10 9 /L in a healthy newborn be considered most suggestive for NAIT and warrant urgent NAIT-specific analysis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to investigate the clinical characteristics, management and prognosis of Bacillus cereus sepsis in premature neonates. The clinical information of 8 premature neonates with B cereus sepsis who were treated in Shanghai Children Hospital from January 2015 to December 2019 was retrospectively collected from the medical records and analyzed. The neurodevelopment related conditions were collected at follow up visits at corrected age of 6 months and 12 months. Five patients developed meningitis, and cerebral magnetic resonance image showed abnormal in 5 patients. After treatment with meropenem and vancomycin, 1 patient died, and 7 patients survived and were smoothly discharged. At follow up visits, 1 patient was diagnosed with hydrocephalus and showed severely delayed neurodevelopment, 2 patients had mild delayed neurodevelopment, and the neurodevelopment was basically normal in remaining 4 patients. B cereus infection can cause severe complications of central nervous system, and affect neurodevelopmental outcome. Antibiotic treatment with meropenem and vancomycin is proven to be effective. Refreshing the central catheters is helpful for the prevention of B cereus sepsis and cerebral magnetic resonance image may be employed for the prognosis assessment., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: In 2016, brief resolved unexplained events (BRUEs) were proposed as alternative concepts to apparent life-threatening event (ALTE). The clinical utility of managing ALTE cases according to the BRUE classification is controversial. To verify the clinical utility of the BRUE criteria, we evaluated the proportion of ALTE patients who met and those who did not meet the BRUE criteria and assessed the diagnoses and outcomes of each group., Methods: We retrospectively investigated patients with ALTE younger than 12 months who visited the emergency department of the National Center for Child Health and Development from April 2008 to March 2020. The patients were classified into the higher-risk and lower-risk BRUE groups; however, those who did not meet the BRUE criteria were classified into the ALTE-not-BRUE group. We evaluated the diagnoses and outcomes of each group. Adverse outcomes included death, recurrence, aspiration, choking, trauma, infection, convulsions, heart disease, metabolic disease, allergies, and others., Results: Over the period of 12 years, a total of 192 patients were included, among which 140 patients (71%) were classified into the ALTE-not-BRUE group, 43 (22%) into the higher-risk BRUE group, and 9 (5%) into the lower-risk BRUE group. Adverse outcomes occurred in 27 patients in the ALTE-not-BRUE group and 10 patients in the higher-risk BRUE group. No adverse outcome occurred in the lower-risk BRUE group., Conclusions: Many of the patients with ALTE were classified into the ALTE-not-BRUE group, suggesting that replacing ALTE with BRUE is difficult. Although patients classified as lower-risk BRUE showed no adverse outcomes, there were only a few of them. In the pediatric emergency medicine setting, the BRUE risk classification may be beneficial for certain patients., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Seizures are common during neonatal encephalopathy (NE), but the contribution of seizure burden (SB) to outcomes remains controversial. This study aims to examine the relationship between electrographic SB and neurologic outcomes after NE., Methods: This prospective cohort study recruited newborns ≥36 weeks postmenstrual age around 6 hours of life between August 2014 and November 2019 from a neonatal intensive care unit (NICU). Participants underwent continuous electroencephalography for at least 48 hours, brain MRI within 3-5 days of life, and structured follow-up at 18 months. Electrographic seizures were identified by board-certified neurophysiologists and quantified as total SB and maximum hourly SB. A medication exposure score was calculated based on all antiseizure medications given during NICU admission. Brain MRI injury severity was classified based on basal ganglia and watershed scores. Developmental outcomes were measured using the Bayley Scales of Infant Development, Third Edition. Multivariable regression analyses were performed, adjusting for significant potential confounders., Results: Of 108 enrolled infants, 98 had continuous EEG (cEEG) and MRI data collected, of which 5 were lost to follow-up, and 6 died before age 18 months. All infants with moderate-severe encephalopathy completed therapeutic hypothermia. cEEG-confirmed neonatal seizures occurred in 21 (24%) newborns, with a total SB mean of 12.5 ± 36.4 minutes and a maximum hourly SB mean of 4 ± 10 min/h. After adjusting for MRI brain injury severity and medication exposure, total SB was significantly associated with lower cognitive (-0.21, 95% CI -0.33 to -0.08, p = 0.002) and language (-0.25, 95% CI -0.39 to -0.11, p = 0.001) scores at 18 months. Total SB of 60 minutes was associated with 15-point decline in language scores and 70 minutes for cognitive scores. However, SB was not significantly associated with epilepsy, neuromotor score, or cerebral palsy ( p > 0.1)., Discussion: Higher SB during NE was independently associated with worse cognitive and language scores at 18 months, even after adjusting for exposure to antiseizure medications and severity of brain injury. These observations support the hypothesis that neonatal seizures occurring during NE independently contribute to long-term outcomes., (© 2023 American Academy of Neurology.)

Diencephalic syndrome is usually associated with tumors in the hypothalamic region, rarely occurring in patients with neurofibromatosis type 1 (NF1)-associated gliomas. We describe the clinical presentation and response to treatment in 3 patients with NF1 presenting with diencephalic syndrome as first symptom of optic pathway/hypothalamic glioma (OPHG). Because of the rarity of this constellation, knowledge about the clinical course and best treatment options for patients with NF1-associated OPHG and diencephalic syndrome is still limited. All 3 patients showed good response to treatment with normalization of body mass index and decrease in tumor volume within 6 months., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

To estimate the relationship among the cesarean delivery (CD), mortality and morbidity in very low birth weight (VLBW) infants weighing less than 1500 g. This retrospective cohort study enrolled 242 VLBW infants delivered between the 24 to 31week of gestation from 2015 to 2021. We compared CD with vaginal delivery (VD). The primary outcome was a composite neonatal morbidity including bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, late-onset sepsis and retinopathy of prematurity. The secondary outcome included mortality within 28 days. A multivariate logistic regression was used and adjusted for birthweight, twin pregnancy and antenatal steroids intake. The overall CD rate was 80.6%. Compared with VD, a significantly lower composite neonatal morbidity was associated with CD (adjusted odds ratio, 0.33, 95% confidence interval, 0.12-0.90, P = .031). The relationship between CD and neonatal morbidity disappeared when the VLBW infants were stratified according to the gestational age. No significant difference was observed between the VD and CD cohorts regarding mortality. Compared with VD, CD was associated with a lower morbidity in VLBW infants. Further studies are required to clarify how this association is influenced by gestational age., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The appropriate timing of delivery for pregnancies has always been a concern for medical staff, and the timing of elective labor induction at 41 weeks in low-risk pregnant women has always been controversial. We compared maternal and fetal outcomes between gestational age at 40 0/7 to 40 6/7 and 41 0/7 to 41 6/7 weeks. This retrospective cohort study was conducted at the obstetrics department of Jiangsu Province Hospital from January 1st to December 31st in 2020. Maternal medical records and neonatal delivery data were collected. One-way analysis of variance, Mann-Whitney U test, χ2 test, Fisher exact test and logistig regression analysis were performed. The study included 1569 pregnancies, with 1107 (70.6%) delivered at 40 0/7 to 40 6/7 weeks and 462 (29.4%) delivered at 41 0/7 to 41 6/7 weeks. Intrapartum cesarean section (8% vs 16%, P < .001), meconium-stained amniotic fluid (13% vs 19%, P = .004), episiotomy (41% vs 49%, P = .011), and macrosomia (13% vs 18%, P = .026) were significantly lower at 40 0/7 to 40 6/7 weeks. The premature rupture of membranes rate (22% vs 12%, P < .001), vaginal delivery rate of artificial rupture of membrane induction (83% vs 71%, P = .006) and balloon catheter combined with oxytocin induction (88% vs 79%, P = .049) were significantly higher at 40 0/7 to 40 6/7 weeks. Low-risk women who delivered at 40 0/7 to 40 6/7 weeks showed better outcomes in terms of the mother's and baby's health, such as decreased rates of intrapartum cesarean section, meconium-stained amniotic fluid, episiotomy, and macrosomia, compared with those who delivered at 41 0/7 to 41 6/7 weeks., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To report temporal trends in venovenous extracorporeal membrane oxygenation (ECMO) use for neonatal respiratory failure in U.S. centers before and after functional venovenous cannula shortage due to withdrawal of one dual lumen venovenous cannula from the market in 2018., Design: Retrospective cohort study., Setting: ECMO registry of the Extracorporeal Life Support Organization., Patients: Infants who received neonatal (cannulated prior to 29 d of age) respiratory ECMO at a U.S. center and had a record available in the ECMO registry from January 1, 2010 to July 20, 2021., Interventions: None., Measurements and Main Results: Primary outcome was receipt of venovenous ECMO (vs venoarterial or other), and secondary outcomes were survival to hospital discharge and adverse neurologic outcomes. Using an interrupted time series design, we fit multivariable mixed effects logistic regression models with receipt of venovenous ECMO as the dependent variable, treatment year modeled as a piecewise linear variable using three linear splines (pre shortage: 2010-2014, 2014-2018; shortage: 2018-2021), and adjusted for center clustering and multiple covariates. We evaluated trends in venovenous ECMO use by primary diagnosis including congenital diaphragmatic hernia, meconium aspiration, pulmonary hypertension, and other. Annual neonatal venovenous ECMO rates decreased after 2018: from 2010 to 2014, adjusted odds ratio (aOR) for yearly trend 0.98 (95% CI 0.92-1.04), from 2014 to 2018, aOR for yearly trend 0.90 (95% CI 0.80-1.01), and after 2018, aOR for yearly trend 0.46 (95% CI 0.37-0.57). We identified decreased venovenous ECMO use after 2018 in all diagnoses evaluated, and we failed to identify differences in temporal trends between diagnoses. Survival and adverse neurologic outcomes were unchanged across the study periods., Conclusions: Venovenous ECMO for neonatal respiratory failure in U.S. centers decreased after 2018 even after accounting for temporal trends, coincident with withdrawal of one of two venovenous cannulas from the market., Competing Interests: Dr. Hatch was supported by a Gerber Foundation Research Award during the time this study was conducted. The first draft of the manuscript was written by Dr. Hatch. Dr. Patrick’s institution received funding from the National Institute on Drug Abuse, the Centers for Medicare and Medicaid and Innovation, the National Institute of Child Health and Human Development, the Robert Wood Johnson Foundation, the National Institute of Mental Health, and The Boedecker Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Abstract: Omphalitis is an uncommon but potentially serious infection in neonates. Findings include erythema and induration around the umbilical stump, and purulent drainage may be present. Fever and signs of systemic illness may occur, or there may only be signs of localized soft tissue infection. Until recently, there have been very few cohort studies of omphalitis in high-income countries, and no literature was available regarding the incidence of concurrent serious bacterial infection such as meningitis or urinary tract infection. A recent large, multicenter study suggests that most omphalitis presents as localized soft tissue infection, with very low rates of concurrent serious bacterial infection or adverse outcomes. Underlying urachal abnormalities should be considered in the infant with umbilical drainage. Treatment of omphalitis consists primarily of antibiotic administration, with surgical intervention rarely needed. Although antibiotics are typically administered intravenously, there may be a role for oral antibiotics in some lower risk infants with omphalitis., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Probiotics are gradually being used as a supplementation to prevent necrotizing enterocolitis (NEC) and reduce mortality in neonates. We performed an updated meta-analysis to systematically evaluate the efficacy and safety of prophylactic probiotic supplementation for preventing NEC., Methods: The databases including PubMed, Embase, Scopus, Web of Science, and China National Knowledge Infrastructure were used to search the relevant articles. The latest retrieval date was up to December 2021. The meta-analysis was performed using Stata version 10.0. Finally, a total of 70 studies containing 8319 cases and 9283 controls were included. The strength of the association between the supplementation of probiotics and NEC was measured by risk ratios (RRs) with 95% confidence intervals (CIs). Pooled effect sizes across studies were performed by a random effect model., Results: The results showed that the probiotics could significantly reduce the incidence of NEC (stage II or more) (RR = 0.436, 95% CI = 0.357-0.531, P < .001), the overall mortality (RR = 0.651, 95% CI = 0.506-0.836, P < .001), and NEC-related mortality (RR = 0.639, 95% CI = 0.423-0.966, P = .034). Due to the lack of sufficient sample size, we did not perform the subgroup analysis by types of probiotic strain., Conclusion: This meta-analysis indicates that the use of probiotics can effectively reduce the occurrence of NEC and mortality in neonates., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To assess the association between allostatic load, as an estimate of chronic stress, and adverse pregnancy outcomes., Methods: This was a secondary analysis of nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be), a prospective observational cohort study. Our primary exposure was dichotomous high allostatic load in the first trimester, defined as 4 or more of 12 biomarkers in the "worst" quartile. The primary outcome was a composite adverse pregnancy outcome: hypertensive disorders of pregnancy (HDP), preterm birth, small for gestational age (SGA), and stillbirth. Secondary outcomes included components of the composite. Multivariable logistic regression was used to test the association between high allostatic load and adverse pregnancy outcomes, adjusted for potential confounders. Mediation and moderation analyses were conducted to assess the role of allostatic load along the causal pathway between racial disparities and adverse pregnancy outcomes., Results: Among 4,266 individuals, 34.7% had a high allostatic load. Composite adverse pregnancy outcome occurred in 1,171 (27.5%): 14.0% HDP, 8.6% preterm birth (48.0% spontaneous and 52.2% indicated), 11.0% SGA, and 0.3% stillbirth. After adjustment for maternal age, gravidity, smoking, bleeding in the first trimester, and health insurance, high allostatic load was significantly associated with a composite adverse pregnancy outcome (adjusted odds ratio [aOR] 1.5, 95% CI 1.3, 1.7) and HDP (aOR 2.5, 95% CI 2.0-2.9), but not preterm birth or SGA. High allostatic load partially mediated the association between self-reported race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race, but not for a composite adverse pregnancy outcome, preterm birth, or SGA., Conclusion: High allostatic load in the first trimester is associated with adverse pregnancy outcomes, particularly HDP. Allostatic load was a partial mediator between race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Management of hemolytic disease of the fetus and newborn relies on monitoring of maternal antibody titers, fetal ultrasound, and fetal middle cerebral artery peak systolic velocity studies and is generally treated by intrauterine transfusion (IUT). Few studies have explored fetal and neonate physiological responses to IUT. Our objective was to examine fetal erythropoietic response and to examine neonatal erythropoietic effects after treatment. Thirty-six patients treated from 2005 to 2015 were identified retroactively. The time course of treatment, including gestational age and number of IUT, and timing of delivery were reviewed. Fetal reticulocyte count and neonatal hemoglobin and reticulocyte counts were analyzed for each IUT. For each gestational week, reticulocyte count decreased by ∼8.6% (95% confidence interval [CI]: 5.3-12.0). In the neonatal period, there was significant correlation between hemoglobin at birth and number of transfusions (Spearman correlation 0.473, 95% CI: 0.113-0.715, P =0.01) as well as reticulocyte count at birth and number of transfusions (Spearman correlation: 0.393, 95% CI: 0.058-0.642, P =0.02). IUT appears to have a direct and measurable effect on fetal reticulocyte production which persists in neonates., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: An increasing number of periviable birth newborns (PVBs) have emerged with concurrent growing high-risk pregnancy. To date, postnatal management of PVBs remains one of the most challenging issues and limited studies have been reported., Patient Concerns: A female baby born at 230/7 weeks of gestation with birth weight of 450g., Diagnosis: PVB baby, respiratory distress syndrome (RDS), ventilator associated pneumonia (VAP), intraventricular hemorrhage (IVH), metabolic bone disease of prematurity (MBDP), transient hypothyroxinemia of prematurity (THOP), bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP)., Interventions: Individualized treatment and intensive care, including neonatal resuscitation, effective respiratory and circulatory support, venous access and nutrition, prevention and treatment of infection, management of endocrine and metabolic problems, individualized nursing such as developmental supportive care, integrated oral motor interventions, skin care, family-integrated-care, etc were performed according to existing literature., Outcomes: The baby was discharged home after 138 days of hospitalization with body weight of 2700 g, a full oral feed achieved, and without any requirement of respiratory support or oxygen supply. Now she is 38-month-old, with no significant long-term adverse sequelae., Lessons: Our case expands the experience and knowledges of individualized and intensive management of PVB babies in their early life days, which increase PVBs' survival and improves their prognosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: The author reports no conflicts of interest.

Gastroschisis is a common congenital abdominal wall defect, likely influenced by environmental factors in utero, with increasing prevalence in the United States. Early detection of gastroschisis in utero has become the standard with improved prenatal care and screening. There are multiple surgical management techniques, though sutureless closure is being used more frequently. Postoperative feeding difficulty is common and requires vigilance for complications, such as necrotizing enterocolitis. Infants with simple gastroschisis are expected to have eventual catch-up growth and normal development, while those with complex gastroschisis have higher morbidity and mortality. Management requires collaboration amongst several perinatal disciplines, including obstetrics, maternal fetal medicine, neonatology, pediatric surgery, and pediatric gastroenterology for optimal care and long-term outcomes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: To assess whether antenatal corticosteroid treatment is associated with improved neonatal outcomes in twins., Data Sources: We searched MEDLINE, PubMed, EMBASE, and the Cochrane Library, from inception through August 12, 2021. We did not search ClinicalTrials.gov because our inclusion criteria were restricted to nonrandomized studies., Methods of Study Selection: Records (n=7,802) were screened in Rayyan by two independent reviewers. We included all nonrandomized studies that compared antenatal corticosteroid treatment with no treatment in twins. Our outcomes of interest were neonatal mortality, respiratory distress syndrome (RDS), intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, periventricular leukomalacia, and retinopathy of prematurity., Tabulation, Integration, and Results: We used the ROBINS-I tool (Risk Of Bias In Non-randomised Studies - of Interventions) to assess risk of bias. We performed random-effects meta-analyses of estimates from studies without critical risk of bias due to confounding, and reported summary adjusted odds ratios (aORs) and 95% CIs. Eighteen cohort studies (that reported on 33,152 neonates) met inclusion criteria. Sixteen studies restricted to preterm gestational ages, and 11 defined exposed neonates based on an optimal corticosteroid administration-to-birth interval. Limitations due to confounding and selection bias were common concerns for the risk-of-bias assessments (n=14 at critical or higher), and 11 studies did not account for clustering within twin pairs in their analyses. All included studies had at least moderate risk of bias. Meta-analysis showed that antenatal corticosteroid administration was associated with lower odds of neonatal mortality (aOR 0.59, 95% CI 0.43-0.80, I2 69%, five studies, 20,312 neonates) and RDS (aOR 0.70, 95% CI 0.57-0.86, I2 67%, seven studies, 20,628 neonates) in twins. Results were inconclusive for the other outcomes., Conclusion: Evidence from nonrandomized studies suggests antenatal corticosteroids are associated with lower incidence of neonatal mortality and RDS in twins., Systematic Review Registration: PROSPERO, CRD42020205302., Competing Interests: Financial Disclosure Sohinee Bhattacharya reports that money was paid to their institution from Tenovus Scotland, Medical Research Scotland, and MRC. They are a collaborator on the Co-Opt project funded by Wellcome Trust and led by the University of Edinburgh. This project aims to look at the effects of antenatal corticosteroids on neonatal outcomes using IPD meta-analysis. The remaining authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies., Data Sources: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded., Methods of Study Selection: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs., Tabulation, Integration, and Results: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward., Conclusion: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone., Systematic Review Registration: PROSPERO, CRD42018090866., Competing Interests: Financial Disclosure Elena Carreras is a member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA (EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516). One included research project was supported, in part, by the Division of Population Health, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and, in part, with federal funds for the NICHD Fetal Growth Studies – Dichorionic Twins under Contract Numbers: HHSN275200800013C; HHSN275200800002I; HHSN27500006; HHSN275200800003IC; HHSN275200800014C; HHSN275200800012C; HHSN275200800028C; and HHSN275201000009C. Katherine L. Grantz has contributed to this work as part of her official duties as an employee of the United States federal government. Wessel Ganzevoort reports government funding (ZonMW 843002825) and free-of-charge test kits from Roche Diagnostics. Sanne J. Gordijn disclosed that money was paid to their institution from ZonMW, Roche (in-kind kits unrestricted and shipping and handling of material), and SCEM (conference payment to research fund). They also received funding from Dublin Maternity Hospital (payment for travels for Charter Day lecture). In addition, they report holding government funding (ZonMW 852002034) and free-of-charge test kits from Roche Diagnostics. R. Katie Morris disclosed money was paid to her through a consultancy to a company that designs neonatal vital signs monitors (SUREPULSE), and money was paid to her institution from the NIHR. Ben W. Mol is supported by a NHMRC Investigator grant (GNT1176437), and reports consultancy for ObsEva and research funding from Ferring and Merck. The PREDICT study received funding from The Danish Medical Research Council, The Fetal Medicine Foundation, The Copenhagen University Hospital's Research Fund, The Aase and Ejnar Danielsens Fund, The Augustinus Fund, The Ivan Nielsen Fund, The Doctor Sofus Carl Emil Friis, and wife Olga Doris Friis' Fund, The Simon Fougner Hartmanns Family Fund, The Danish Medical Society in Copenhagen, and The A.P. Moeller Foundation. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To estimate whether low-dose aspirin use is associated with an altered risk of delivering a small-for-gestational age (SGA) neonate among women with a history of having an SGA neonate in a prior pregnancy., Methods: We performed a Swedish register-based cohort study including women in their second pregnancy who had a history of having an SGA neonate (birth weight less than the 10th percentile). The association between use of low-dose aspirin in subsequent pregnancy and birth of an SGA neonate or a severely SGA neonate (birth weight less than the third percentile) were estimated using inverse propensity-weighted estimation, accounting for potential confounders., Results: Among 8,416 women who gave birth to an SGA neonate in their first pregnancy, 801 (9.5%) used low-dose aspirin during their second pregnancy. The incidence of SGA neonates was similar among women using low-dose aspirin (21.7%) and those who did not use aspirin (20.7%). Low-dose aspirin use in pregnancy was not associated with an altered risk of having an SGA neonate (adjusted relative risk [aRR] 0.86, 95% CI 0.67-1.10) or a severely SGA neonate (aRR 0.98, 95% CI 0.71-1.34). Given the strong association between preeclampsia and SGA, we performed subgroup analyses based on preeclampsia status. Among women who had an SGA neonate and co-existing preeclampsia in their first pregnancy, low-dose aspirin was not associated with an altered risk of having an SGA (aRR 0.83, 95% CI 0.63-1.10) or severely SGA (aRR 1.02, 95% CI 0.73-1.44) neonate. Additionally, no association was seen among women who developed preeclampsia in their second pregnancy., Conclusion: Among women with a history of having an SGA neonate, low-dose aspirin was not associated with a decreased risk of having an SGA or severely SGA neonate in subsequent pregnancy. These findings suggest that low-dose aspirin should not be used to prevent recurrent SGA., Competing Interests: Financial Disclosure: Stephen Tong is a board member of the Menzies Research Institute of Medical Research. Lina Bergman collaborates with Perkin Elmer, Roche and Termo Fischer in a prediction trial of preeclampsia where the companies provide the study with PlGF reagents. However, the companies have no role in the design of that study and it is not related to this work. Susanne Hesselman reports for serving on an advisory board for Baxter Medical AB outside the submitted work. The other authors did not report any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Black infants have twice the incidence of infant mortality (IM), death before the first birthday, and preterm birth in comparison to other US racial/ethnic groups; these factors make Black infants a high-risk group. The literature on the factors impacting caregivers and home environments for these infants is sparse. The purpose of this descriptive qualitative study was to explore perceived parental readiness to care for their Black preterm infants at home after discharge from a neonatal intensive care unit (NICU). Ten NICU parents of Black preterm infants completed a structured interview and self-report questionnaires before hospital discharge; data were analyzed using descriptive and semantic content methods. Coded parent responses were categorized as Parent Protector of Infants' Health (n = 94, 29.2%); Hindrances to Parental Readiness for Transition to Home (n = 97, 30.1%), and Parent as Partner in NICU to Home Transition (n = 131, 40.6%). All parents rated themselves "confident" (n = 6) or "very confident" (n = 4) in their ability to care for their infant after NICU discharge. Partnership with the healthcare team was described as involving health information resources, effective communication, and, most importantly, support for the parental role as infant protector for transition to home for their high-risk infant after NICU discharge., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

What Was Observed or Investigated: The increased morbidity of diverse infants is unacceptable, and methods to reduce necrotizing enterocolitis (NEC) in their communities are needed. This article discusses the importance of the Español toolkit; provides a backstory of how the Español toolkit came about and how it was verified and validated; and concludes with impressions from involving parents in the research process., Subjects and Methods: After research evidence was translated from English into Spanish, a cross-sectional exploratory, descriptive, mixed-methods study was conducted, guided by the knowledge translation into practice (Translating Research Into Practice [TRIP]) framework. Twenty bilingual English-Spanish parents of fragile infants evaluated the NEC-Zero Español toolkit from a single neonatal intensive care unit., Results and Conclusions: The NEC-Zero Español toolkit was found to be easy-to-use and useful and provided information that can be used to augment information sharing. Having access to health information offers a meaningful way to start a conversation and may even impact positive behaviors such as breastfeeding promotion. To lessen Spanish speakers' linguistic barriers, providing materials in Spanish can help meet their information needs and initiate conversations with healthcare providers. This is particularly important because Hispanic infants are at high risk for NEC., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine whether screening continuous EEG monitoring (cEEG) is associated with greater odds of treatment success for neonatal seizures., Methods: We included term neonates with acute symptomatic seizures enrolled in the Neonatal Seizure Registry (NSR), a prospective, multicenter cohort of neonates with seizures. We compared 2 cEEG approaches: (1) screening cEEG, initiated for indications of encephalopathy or paralysis without suspected clinical seizures; and (2) confirmatory cEEG, initiated for the indication of clinical events suspicious for seizures, either alone or in addition to other indications. The primary outcome was successful response to initial seizure treatment, defined as seizures resolved without recurrence within 30 minutes after initial loading dose of antiseizure medicine. Multivariable logistic regression analyses assessed the association between cEEG approach and successful seizure treatment., Results: Among 514 neonates included, 161 (31%) had screening cEEG and 353 (69%) had confirmatory cEEG. Neonates with screening cEEG had a higher proportion of successful initial seizure treatment than neonates with confirmatory cEEG (39% vs 18%; p < 0.0001). After adjusting for covariates, there remained a greater odds ratio (OR) for successful initial seizure treatment in the screening vs confirmatory cEEG groups (adjusted OR 2.44, 95% confidence interval 1.45-4.11, p = 0.0008)., Conclusions: These findings provide evidence from a large, contemporary cohort of neonates that a screening cEEG approach may improve odds of successful treatment of acute seizures., Classification of Evidence: This study provides Class III evidence that for neonates a screening cEEG approach, compared to a confirmatory EEG approach, increases the probability of successful treatment of acute seizures., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objectives: Exchange transfusion (ET) and intravenous immunoglobulin are potentially life-saving treatment options in newborns with gestational alloimmune liver disease (GALD). Since 2008, early ET has been the standard of care for symptomatic neonates with suspected GALD in our unit. The present study's aim was to investigate the outcomes of this approach., Methods: From 2008 to 2018, all neonates who received ET for suspected GALD were identified, and their clinical course and outcomes were analyzed in a descriptive cohort study. In survivors, liver function parameters before ET and maximum values after ET and at discharge were compared., Results: During the 11-year period, 12 infants received ET for suspected GALD at a median (range) chronological age of 11 (1-23) days and gestational age of 38 (32-40) weeks. Signs of impaired liver function, most frequently postnatal hypoglycemia, hyperferritinemia, direct hyperbilirubinemia, and coagulopathy, were present in all infants. Survival without a liver transplant in the overall cohort was 10 of 12 (83.3%) and 7 of 9 (78%) in those fulfilling the criteria of acute liver failure. Two patients died, one of them after liver transplantation. Direct bilirubin typically increased after ET, even in survivors. All survivors recovered and were discharged from the pediatric hepatology outpatient clinic after 8 (3-11) months of follow-up., Conclusions: In newborns with suspected GALD, a limited diagnostic work-up followed by early ET may lead to favorable outcomes. More data are required to develop an evidence-based clinical approach to GALD.

Background and Purpose- In infants with perinatal arterial ischemic stroke (PAIS), early prognosis of neurodevelopmental outcome is important to adequately inform parents and caretakers. Early continuous neuromonitoring after PAIS may improve early prognosis. Our aim was to study early cerebral electrical activity and oxygenation measured by amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in term neonates with PAIS and relate these to the development of cerebral palsy and cognitive deficit. Methods- aEEG patterns and regional cerebral oxygen saturation (rScO 2 ) levels of both hemispheres were studied for 120 hours from the first clinical symptoms of PAIS (ie, seizures) onward. Multivariable analyses were used to investigate the association between aEEG, near-infrared spectroscopy, clinical variables, and neurodevelopmental outcome. Results- In 52 patients with PAIS (gestational age, 40.4±1.4 weeks; birth weight, 3282±479 g), median time to a continuous background pattern was longer in the ipsilesional compared with the contralesional hemisphere (13.5 versus 10.0 hours; P <0.05). rScO 2 decreased over time in both hemispheres but less in the ipsilesional one, resulting in a rScO 2 asymmetry ratio of 4.5% (interquartile range, -4.3% to 5.9%; P <0.05) between hemispheres from day 3 after symptoms onward. Both time to normal background pattern and asymmetry in rScO 2 were negatively affected by gestational age, size of the PAIS, use of antiepileptic drugs, and mechanical ventilation. After correction for size of the PAIS on magnetic resonance imaging, a slower recovery of background pattern on ipsilesional aEEG and increased rScO 2 asymmetry between hemispheres was related with an increased risk for cognitive deficit (<-1 SD) at a median of 24.0 (interquartile range, 18.4-24.4) months of age. Conclusions- Recovery of background pattern on aEEG and cerebral oxygenation are both affected by PAIS and related to neurocognitive development. Both measurements may provide valuable early prognostic information. Additionally, monitoring cerebral activity and oxygenation may be useful in identifying infants eligible for early neuroprotective interventions and to detect early effects of these interventions.

Purpose of Review: The purpose of this review is to discuss evolving research into intestinal inflammatory responses as they relate to the developing microbiome and to provide insights into developing multiomic tools that are being used to describe these relationships. Intestinal inflammatory conditions are common, and in the neonate present special challenges, especially in the form of necrotizing enterocolitis (NEC) and other conditions that involve damage or breakdown of the mucosal barrier, leading to systemic inflammation and damage to distal sites, such as the liver and brain., Recent Findings: Recent studies show that when a dysbiosis (microbial imbalance or impaired microbiota) occurs, an inflammatory response that can affect the entire body is frequently the result. We are recognizing that not only the microbial diversity and relative abundance of certain taxa play a role in dysbiosis and inflammation, but their functional capabilities in terms of metabolite production and interaction with the immune system of the host afre critical in future health and disease., Summary: A multiomic approach to evaluate these microorgansims as well as their interaction with the host by using systems-based concepts is becoming possible and is likely to shed new light on various disease entities and how we can best prevent and treat them.