Radial nerve palsy caused by a rapidly growing intramuscular hematoma in an infant with biliary atresia: a case report.

BACKGROUND: Biliary atresia (BA) is a rare cause of persistent jaundice in infants that can result in vitamin K malabsorption and vitamin K deficiency bleeding (VKDB). We present an infant with BA who developed a rapidly growing intramuscular hematoma in her upper arm after a vaccination which caused a radial nerve palsy. CASE PRESENTATION: An 82-day-old girl was referred to our hospital because of a rapidly growing left upper arm mass. She had received three doses of oral vitamin K before age 1 month. At age 66 days, she received a pneumococcal vaccination in her left upper arm. On presentation, she showed no left wrist or finger extension. Blood examination revealed direct hyperbilirubinemia, liver dysfunction, and coagulation abnormalities, indicating obstructive jaundice. Magnetic resonance imaging showed a hematoma in the left triceps brachii. Abdominal ultrasonography revealed an atrophic gallbladder and the triangular cord sign anterior to the portal vein bifurcation. BA was confirmed on cholangiography. VKDB resulting from BA in conjunction with vaccination in the left upper arm were considered the cause of the hematoma. The hematoma was considered the cause of her radial nerve palsy. Although she underwent Kasai hepatic portoenterostomy at age 82 days, the obstructive jaundice did not sufficiently improve. She then underwent living-related liver transplantation at age 8 months. The wrist drop was still present at age 1 year despite hematoma resolution. CONCLUSIONS: Delayed detection of BA and inadequate prevention of VKDB can result in permanent peripheral neuropathy.

Medical records as screening tools for child death review in Japan.

BACKGROUND: Although many child death review (CDR) systems have been developed in Japan, the optimal system is still being identified. The aim of this study is to identify the etiologies of child deaths and to propose a screening method for initiating the CDR process in Japan. METHODS: Clinical medical records (CMRs) in hospitals and autopsy records were surveyed for cases of deaths of children aged less than 15 years between 2014 and 2016 in Aichi Prefecture, Japan. The data were analyzed in three steps, and the findings were compared with the vital statistics. RESULTS: Of the 695 children whose death certificates were submitted to Aichi Prefecture, 590 could be traced to pediatric care hospitals. The distribution of causes of death was slightly different from the vital statistics, with 11.5% dying of extrinsic causes and 19.7% dying of unknown causes. Maltreatment was suspected in 64 cases, which was much higher than that in government statistics. Overall, 158 (26.8%) deaths were considered preventable. The number of unnatural deaths, which might be screened in, was calculated as 172 (29.2%) in the vital statistics, whereas the survey of CMRs revealed that 241 (40.8%) to 282 (47.8%) should be screened in. CONCLUSIONS: Surveying CMRs in hospitals may be a suitable method to detect and screen deaths to start the CDR process in Japan.

Current status of neonatal jaundice management in Japan.

BACKGROUND: This nationwide survey aimed to determine the status of jaundice management in Japan. METHODS: A questionnaire about bilirubin level measurements and neonatal jaundice treatment was sent to 330 institutions providing neonatal care. The responses were analyzed according to institution level. RESULTS: Of 330 institutions, 172 responded (52.1% response rate). Total bilirubin levels were measured in the central laboratory using spectrophotometry at 134 institutions and a blood gas analyzer at 81 institutions. Unbound bilirubin (UB) levels were measured by 79 institutions, while transcutaneous bilirubin measurements were taken at 63 institutions. There was no association between institution level and UB or transcutaneous bilirubin measurement. For phototherapy criteria, the Murata-Imura criteria were adopted by 67 institutions, Nakamura criteria by 36, and Morioka criteria by 39. Light-emitting diodes (LED) were used by 160 institutions versus fluorescent lights by 31. When a blue LED was used, 119 institutions used the high mode. There is no standard for increasing light intensity. No association was found between institution level and phototherapy criteria. UB was measured in 14 of 63 institutions using the Murata-Imura criteria. CONCLUSIONS: There is a large variation in the management and treatment of neonatal jaundice among institutes in Japan.

Death review of children receiving medical care at home.

BACKGROUND: Children receiving home medical care need special attention to prevent unexpected death. The aim of this study was to clarify the factors contributing to death in children receiving home medical care from the child death review database. METHODS: Children receiving home medical care were enrolled from the child death review database from 2014 to 2016 in Aichi prefecture, Japan, with a population of one million children. Types of medical care and factors contributing to death were examined. RESULTS: Of the 631 children who died, 40 children (6%) were receiving home medical care (21: tracheostomy; 19: ventilator; 26: suctioning of naso-oral secretions; 19: oxygen inhalation; 32: tube feeding; 6: urethral catheterization; and 1: peritoneal dialysis). The death rate was 50 times that in the general population of children. Ten children had contributory factors that seemed to be preventable. In four children, the families could not replace the tracheostomy tubes during an accident. In three, oxygen saturation or ventilator alarms were not set appropriately. In two, an oxygen cylinder became empty. One child fell down from a seat in a car. CONCLUSIONS: Improvement of devices and correct guidance to caregivers may reduce the death rate in children receiving home medical care. IMPACT: Children receiving home medical care, such as tracheostomy care, mechanical ventilation, or tube feeding, need special attention to prevent unexpected death. In this population-based child death review, 6% of children received home medical care, and it was estimated that 1 of 100 children receiving home medical care died per year. One-quarter of the deaths could be preventable by caregiver education or development of devices.

Hypersensitivity reaction to high-dose methotrexate and methotrexate-induced acral erythema in a child with acute lymphoblastic leukemia.

A 9-year-old boy with acute lymphoblastic leukemia experienced a hypersensitivity reaction (HSR) and acral erythema upon receiving high-dose methotrexate (HDMTX). Both HSR and acral erythema are uncommon adverse events of MTX therapy, and MTX has not been reported to cause HSRs in specific ethnic groups. We assessed the severity of each symptom and were successful in managing these adverse events for continuing subsequent HDMTX therapies. HSR appeared during the first and second HDMTX courses. Acral erythema occurred after the second and fourth courses. Desensitization by reducing the infusion rate and premedication allowed the continuation of HDMTX. Acral erythema improved with supportive care without dose reduction or interval lengthening. HSRs to MTX should be considered even during the first course. MTX-induced acral erythema is a self-limited reaction; therefore, the chemotherapeutic regimen should not be modified unless necessary.

Effects of maternal magnesium sulfate treatment on newborns.

BACKGROUND: Antenatal magnesium sulfate (MgSO4 ) has been used with mothers, but the influence of MgSO4 on the fetus is unclear. The purpose of this study is to determine whether longer antenatal MgSO4 exposure correlates with adverse effects in newborns. METHODS: The clinical data of 77 infants born to mothers treated with MgSO4 were collected. The infants were divided into two groups according to (1) the serum Mg concentration, (2) cumulative Mg dose, and (3) duration of antenatal maternal Mg treatment, respectively. RESULTS: The serum Mg level of the infants correlated with that of the mothers but not with the duration of Mg treatment or the cumulative dose of Mg. There were no significant differences in the infants' clinical variables according to either the duration of Mg treatment or the cumulative dose of Mg. By contrast, enteral feeding tolerance began at a significantly later age and the heart rate on admission was significantly lower in infants with a serum Mg level ≥4.0 mmol/L than in those with a serum Mg level <4.0 mmol/L. CONCLUSIONS: Modest effects on the clinical variables of infants with higher serum Mg levels were determined, whereas neither the duration of Mg treatment nor the cumulative Mg dose correlated with the clinical variables of the infants. Thus, in newborns with only moderately elevated serum Mg levels, serious adverse effects are unlikely.

Serum free carnitine levels in children with Kawasaki disease.

BACKGROUND: Carnitine plays an essential role in the transfer of long-chain fatty acids to the mitochondria for ß-oxidation. No study has characterized carnitine in children with Kawasaki disease (KD). The objective of this study was to elucidate the characteristics of serum free carnitine (FC) in hospitalized pediatric patients with KD. METHODS: We retrospectively analyzed 45 patients with KD in whom serum FC levels were measured. We investigated the clinical and laboratory parameters before intravenous immunoglobulin was administered, including serum FC levels, according to the response to intravenous immunoglobulin (IVIG). We also analyzed the relationship among serum FC, laboratory data, and clinical variables. RESULTS: IVIG was effective in 33 children (responders) and was ineffective in 12 children (non-responders). Serum FC levels were higher in non-responders than in responders: 35.3 µmol/L (range, 26.8-118.4 µmol/L) vs 31.4 µmol/L (range, 20.9-81.2 µmol/L), P <0.05. FC levels before IVIG in 80% of responders were below the normal range. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and FC were higher in non-responders than in responders. FC levels were correlated with AST (R2 = 0.364, P = 0.0015) and ALT (R2 = 0.423, P < 0.001) levels. CONCLUSIONS: Free carnitine levels were elevated in some patients with KD, especially in those who were refractory to IVIG. Additionally, FC levels in children with KD correlated with ASL and ALT levels.

Involvement of brain structures in childhood epilepsy with centrotemporal spikes.

BACKGROUND: We aimed to investigate electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) findings to elucidate the interictal epileptiform discharge (IED)-related functional alterations in deep brain structures and the neocortex in childhood epilepsy with centrotemporal spikes (CECTS). METHODS: Ten children with CECTS (median age 8.2 years), referred to our hospital within a year of onset, were eligible for inclusion. They underwent EEG-fMRI recording during sleep. Llongitudinal evaluations, including medical examinations, intelligence tests, and questionnaires about developmental disabilities, were performed. The initial evaluation was performed at the same time as the EEG-fMRI, and the second evaluation was performed over 2 years after the initial evaluation. RESULTS: Three children were unable to maintain sleep during the EEG-fMRI recording, and the remaining seven children were eligible for further assessment. All patients showed unilateral-dominant centrotemporal spikes during scans. One patient had only positive hemodynamic responses, while the others had both positive and negative hemodynamic responses. All patients showed IED-related hemodynamic responses in the bilateral neocortex. For deep brain structures, IED-related hemodynamic responses were observed in the cingulate gyrus (n = 4), basal ganglia (n = 3), thalamus (n = 2), and default mode network (n = 1). Seizure frequencies at the second evaluation were infrequent or absent, and the longitudinal results of intelligence tests and questionnaires were within normal ranges. CONCLUSIONS: We demonstrated that IEDs affect broad brain areas, including deep brain structures such as the cingulate gyrus, basal ganglia, and thalamus. Deep brain structures may play an important role in the pathophysiology of CECTS.

Usefulness of brain natriuretic peptide to distinguish Kawasaki disease from cervical lymphadenitis.

BACKGROUND: Cervical lymphadenitis (CL) cannot be easily distinguished from Kawasaki disease (KD). We therefore explored whether brain natriuretic peptide (BNP) levels are useful in this context. METHODS: We retrospectively analyzed 14 children with CL and 177 children with KD. Patients with KD were divided into three groups according to their clinical symptoms at hospitalization - 97 patients had typical KD, 35 had node-first KD (NFKD), and 45 had KD without lymphadenopathy. We reviewed data on clinical and laboratory parameters, including serum BNP levels, at hospitalization together with factors that might distinguish KD from CL. RESULTS: Patients with CL were older than those with KD. Serum BNP levels were higher in all the KD groups than in the CL group. Multivariate logistic regression analyses indicated that higher BNP levels were associated with NFKD (odds ratio: 1.12, 95% confidence interval: 1.01-1.25). The receiver operating characteristic curve yielded a BNP cutoff of 18.3 pg/mL, with a sensitivity of 0.680, a specificity of 0.857, and an area under the curve of 0.806 (95% confidence interval: 0.665-0.947). CONCLUSIONS: Serum BNP levels can be used to distinguish KD from CL, especially in patients with NFKD.

Epidemiology of child mortality and challenges in child death review in Japan: The Committee on Child Death Review: A Committee Report: The Committee on Child Death Review: A Committee Report.

We performed a retrospective survey and verification of the medical records of death cases of children (and adolescents; aged <18 years) between 2014 and 2016 in pediatric specialty training facilities in Japan. Of the 2,827 registered cases at 163 facilities, 2,348 cases were included. The rate of identified deaths compared with the demographic survey, was 18.2%-21.0% by age group. The breakdown of deaths was determined as follows: 638 cases (27.2%) were due to external factors or unknown causes, 118 (5.0%) were suspected to involve child maltreatment, 932 (39.7%) were of moderate or high preventability or were indeterminable. Further detailed verification was required for 1,333 cases (56.8%). Comparison of the three prefectures with high rates of identified deaths in Japan revealed no significant differences, such as in the distribution of diseases, suggesting that there was little selection bias. The autopsy rate of deaths of unknown cause was 43.4%, indicating a high ratio of forensic autopsies. However, sufficient clinical information was not collected; therefore, thorough evaluations were difficult to perform. Cases with a moderate or high possibility of involvement of child maltreatment accounted for 5%, similar to previous studies. However, more objective evaluation is necessary. Preventable death cases including potentially preventable deaths accounted for 25%, indicating that proposals need to be made for specific preventive measures. Individual primary verification followed by secondary verification by multiple organizations is effective. It is anticipated that a child death review (CDR) system with such a multi-layered structure will be established; however, the following challenges were revealed: The subjects of CDR are all child deaths. Even if natural death cases are entrusted to medical organizations, and complicated cases to other special panels, the numbers are very high. Procedures need to be established to sufficiently verify these cases. Although demographic statistics are useful for identifying all deaths, care must be taken when interpreting such data. Detailed verification of the cause of death will affect the determination of subsequent preventability. Verification based only on clinical information is difficult, so a procedure that collates non-medical information sources should be established. It is necessary to organize the procedures to evaluate the involvement of child maltreatment objectively and raise awareness among practitioners. To propose specific preventive measures, a mechanism to ensure multiprofessional diverse perspectives is crucial, in addition to fostering the foundation of individual practitioners. To implement the proposed measures, it is also necessary to discuss the responsibilities and authority of each organization. Once the CDR system is implemented, verification of the system should be repeated. Efforts to learn from child deaths and prevent deaths that are preventable as much as possible are essential duties of pediatricians. Pediatricians are expected to undertake the identified challenges and promote and lead the implementation of the CDR system. This is a word-for-word translation of the report in J. Jpn. Pediatr. Soc. 2019; 123 (11): 1736-1750, which is available only in the Japanese language.

Effects of l-carnitine supplementation in patients with childhood-onset epilepsy prescribed valproate.

BACKGROUND: The benefits of carnitine supplementation in patients treated with valproate (VPA) are not clear. Therefore, we retrospectively explored the benefits of carnitine supplementation by analyzing laboratory data. METHODS: We measured the serum-free carnitine (FC), VPA, aspartate aminotransferase, alanine aminotransferase, amylase, and ammonia levels, and the platelet count, in 69 patients with childhood-onset epilepsy treated with VPA. Eight patients had received carnitine supplementation. The serum FC and acylcarnitine levels were measured using an enzyme cycling method. We compared laboratory values between patients with and without carnitine supplementation and analyzed the correlations between serum FC levels and laboratory values. RESULTS: The serum FC levels were normal (median, 48.8 µmol/L; range: 41.9-68.3 µmol/L) in all eight patients with carnitine supplementation, but below normal in 32 of 61 patients without supplementation. The median serum amylase levels were lower in the patients with carnitine supplementation (median, 48 U/L; range: 27-149 U/L) than in those without (median, 7 U/L; range: 14-234 U/L). The platelet count and serum ammonia levels did not differ significantly between patients with and without supplementation. There was no significant correlation between the serum FC level and the platelet count, serum amylase level, or ammonia level. CONCLUSIONS: Carnitine supplementation helps maintain serum FC levels in patients treated with VPA. The lower serum amylase levels in patients with carnitine supplementation may reflect protective effects of carnitine against latent pancreatic injury.

Carnitine supplementation prevents carnitine deficiency caused by pivalate-conjugated antibiotics in patients with epilepsy prescribed valproate.

We measured carnitine levels before and after pivalate-conjugated antibiotic (PCA) use in six patients with epilepsy who were prescribed valproate (VPA). Three of the patients were on carnitine supplementation when PCA use started. Serum FC levels were within the normal range (37.2-49.0 µmol/L) in all six patients before PCA use. After PCA use, the serum free carnitine (FC) levels remained within the normal range (48.0-68.2 µmol/L) in all three patients on carnitine supplementation, but were below the normal range (18.7-30.8 µmol/L) in the three patients not on carnitine supplementation. No remarkable changes in serum VPA levels, platelet count, amylase or ammonia level was evident in any patients in relation to PCA use. Carnitine deficiency due to PCA use was prevented by carnitine supplementation in patients with epilepsy who were taking VPA. Carnitine supplementation can support patients at risk of carnitine deficiency.

Repetitive sleep starts: An important differential diagnosis of infantile spasms.

OBJECTIVE: Repetitive sleep starts (RSS) are clusters of nonepileptic, spasm-like movements occurring during sleep onset. However, their characteristics have yet to be defined. We conducted a clinicoelectroencephalographic study of children with RSS to clarify their detailed characteristics. METHODS: To differentiate starts from epileptic spasms, we recruited children with brief "crescendo-decrescendo" muscle contractions that simultaneously involved the limbs and trunk without electroencephalogram changes, and that fulfilled the following criteria: (1) repeated occurrence (five or more) and (2) manifestation during sleep stage N1-N2. A total of nine children met these criteria. Their clinical information and video-electroencephalogram data were analyzed retrospectively. RESULTS: The background conditions observed at onset of RSS were perinatal hypoxic-ischemic encephalopathy (n = 4), West syndrome of unknown etiology (n = 1), and traumatic brain injury (n = 1). The age at onset of RSS, the number of starts in a given RSS cluster, the interval between starts, and the duration of surface electromyogram activity were between 3 and 46 months, 5 and 547, <1 and 60 s, and 0.3 and 5.4 s, respectively. None of the median value of these parameters differed between children with and without corticospinal tract injury. During the median follow-up period of 33 months, RSS disappeared spontaneously in five. CONCLUSION: This is the largest case series of RSS clarifying their clinicoelectroencephalographic characteristics reported to date. To avoid unnecessary antiepileptic therapies, clinicians should be aware of RSS and distinguish it from other disorders involving involuntary movements or seizures, especially epileptic spasms.

Effectiveness of lacosamide in children and young adults previously treated with other sodium channel blockers.

PURPOSE: This multicenter study examined the effectiveness and tolerability of lacosamide (LCM) for children and young adults with epilepsy, particularly in patients who had previously been treated with other sodium channel blockers (SCBs) and the difference in effectiveness and tolerability when using other concomitant SCBs. METHODS: We retrospectively studied the clinical information of patients aged <30 years given LCM to treat epilepsy. The effectiveness and adverse events (AEs) of LCM and the other SCBs were investigated. Factors related to the effectiveness and AEs of LCM, such as the number of antiepileptic drugs (AEDs) tried before LCM and concomitantly used SCBs, were also studied. RESULTS: We enrolled 112 patients (median age = 11 years). One year after starting LCM, 29% of the patients were seizure free, and 50% had a ≥50% seizure reduction. Of the patients, 17% experienced AEs, the most common being somnolence. A ≥50% seizure reduction was observed for LCM in 30% of patients in whom other SCBs had not been effective. Lacosamide produced a ≥50% seizure reduction in 35% of the patients taking one concomitant SCB. By contrast, no patients had ≥50% seizure reduction, and 33% developed AEs, when LCM was administered concomitantly with two SCBs. CONCLUSIONS: Lacosamide was effective in 30% of children and young adults in whom other SCBs had not been effective. The effectiveness of LCM may differ from that of other SCBs, and it is worth trying in patients with epilepsy resistant to other AEDs.

MRI findings in children with congenital cytomegalovirus infection retrospectively diagnosed with dried umbilical cord.

PURPOSE: Brain MRI provides important information about suspected congenital CMV infection in neonatally underdiagnosed children. This study aimed to describe MRI findings in children in whom congenital CMV infection was not suspected during the neonatal period and was proven retrospectively. METHODS: We enrolled 31 children referred to the pediatric neurology clinic with neurological symptoms who were proven to have congenital CMV infection based on dried umbilical cord samples. Upon diagnosis, MR and CT images were assessed using the van der Knaap scoring system integrated with additional variables. Two investigators independently assessed all images. RESULTS: The age at diagnosis was < 12 months in 14, 12-24 months in 11, and > 24 months in 6 patients. The initial symptom triggering clinic referral was delayed development in 22, seizure in 5, deafness in 3, and hemiplegia in 1 patient. Of the 31 children, 30 had a white matter (WM) abnormality predominant in the deep WM of the parietal lobe (n = 25). Anterior temporal lesions were observed in 21 children. Cortical lesions were observed in 7 children, suggestive of polymicrogyria. No child had cerebellar or brainstem abnormalities. Brain CT was performed in 22 of 31 children, and 11 showed punctate cerebral calcification in the periventricular and/or deep WM. CONCLUSION: Patients with congenital CMV infection with delayed neurological symptoms show a relatively uniform pattern of parietal-dominant multifocal WM lesions and anterior temporal lesions, with or without polymicrogyria.

Neonatal intrahepatic cholestasis caused by citrin deficiency with no hepatic steatosis: a case report.

BACKGROUND: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a common form of neonatal jaundice. Histopathological examination of the liver in patients with NICCD typically shows fatty liver, steatohepatitis, and liver fibrosis. Jaundice and fatty liver often improve by 1 year of age. We herein describe a girl who was diagnosed with NICCD based on an SLC25A13 mutation, although no fatty deposits were found on pathologic examination of the liver. CASE PRESENTATION: The patient in this case was a 3-month-old girl. At 2 months of age, she presented with jaundice, discolored stools, and poor weight gain and was found to have hyperbilirubinemia. Cholangiography revealed that she did not have biliary atresia. A laparoscopic liver biopsy was performed, and liver histopathology showed no fatty deposits. Genetic analysis revealed a compound heterozygous mutation in SLC25A13, and she was diagnosed with NICCD. She was given medium-chain triglyceride milk and gained weight. She resumed consumption of normal milk and breast milk, and her stool color improved. She was discharged at 4 months of age with adequate weight gain and a lower total bilirubin concentration. She was in good condition after discharge and showed normal development at the time of outpatient follow-up. CONCLUSIONS: We experienced a case of NICCD in a patient without fatty liver. This case illustrates that the absence of hepatic steatosis in neonatal cholestasis does not rule out NICCD.

A nationwide questionnaire survey on accidental magnet ingestion in children in Japan.

AIM: The aim is to investigate the actual situation of accidental ingestion of magnets in children in Japan and the clinical features of the resulting gastrointestinal damage. METHODS: We developed a questionnaire and sent it to 496 board-certified training hospitals nationwide. Information was collected on the number of children with accidental magnet intake from 2015 to 2017, witnesses of magnet intake, number and type of magnets, presence or absence of gastrointestinal injury, treatment, etc RESULTS: The number of cases of accidental ingestion of magnets within the study period was 104, with a median age of 2 years. About half of the incidents were unwitnessed. There were 33 cases of accidental ingestion of multiple magnets. Among them, oesophagogastroduodenoscopy was performed in 4 children and surgery in 10, and significantly invasive treatment was required in comparison with single-magnet ingestion. Gastrointestinal injury was observed in 11 cases, 10 of which were caused by multiple-magnet ingestion. All 10 of these patients underwent surgical treatment. There was no mortality. CONCLUSION: The incidence of accidental magnet ingestion in Japan is estimated to be 50-70 per year. Unwitnessed cases are not uncommon. Multiple magnet ingestion often causes gastrointestinal injury. Many cases of gastrointestinal injury are caused by ingestion of magnetic toys.

Harlequin syndrome associated with ganglioneuroblastoma-induced Horner syndrome.

A 1-year-old boy presented with a 4-month history of hypertension, ptosis of the right upper eyelid, left hemifacial sweating, and flushing. He was diagnosed with Harlequin syndrome associated with Horner syndrome. Computed tomography revealed a mass lesion in the right superior mediastinum. Therefore, the patient underwent total tumor resection. Histological examination demonstrated ganglioneuroblastoma. The MYCN oncogene was not amplified, and the mitosis-karyorrhexis index was low. Accordingly, radiation and chemotherapy were not performed. No recurrence was observed within 8 months after surgery, and the patient's blood pressure was normalized. However, the ptosis, hemifacial sweating, and flushing persisted.

Acetaminophen elevates unbound bilirubin levels by the glucose oxidase-peroxidase method.

BACKGROUND: Acetaminophen is widely administered to neonates but its effect on unbound bilirubin (UB) levels remains unclear. The aim of this study was to clarify whether administration of acetaminophen is related to an elevation of UB levels. METHOD: Infants with a birthweight of ˂1,500 g admitted to our neonatal intensive care unit between January 2017 and April 2020 were retrospectively reviewed. Seventy-one infants were enrolled, five of whom had received acetaminophen. Clinical data were analyzed when the highest UB value (UB peak) in each infant was recorded. Demographic data and information on treatment within the 24 h before the UB peak were also collected. UB was determined by the glucose oxidase-peroxidase (GOD-POD) method. Infants were categorized according to the presence or absence of acetaminophen administration (acetaminophen and no acetaminophen groups) within 24 h of the UB peak. The relationship between UB values and various clinical variables was then compared. RESULTS: Both the peak UB value and the ratio of gastrointestinal disease were higher in the acetaminophen group than in the no acetaminophen group. Univariate analysis revealed that a total of seven variables were potentially correlated with UB peak values (P < 0.10). Multivariate analysis showed that acetaminophen and direct bilirubin were independently associated with UB peak values. CONCLUSION: Our study suggests that administration of acetaminophen is related to higher UB levels by the GOD-POD method. UB values measured by the GOD-POD method should not be used in infants treated with acetaminophen for evaluation of bilirubin neurotoxicity avoidance.

Pseudo-sawtooth pattern on amplitude-integrated electroencephalography in neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: The objective of this study was to describe a novel amplitude-integrated electroencephalography (aEEG) pattern in infants with hypoxic-ischemic encephalopathy (HIE) and to assess the clinical significance. METHODS: The aEEG traces of infants with HIE who were treated with therapeutic hypothermia (TH) from 2012 to 2017 were analyzed. A pseudo-sawtooth (PST) pattern was defined as a periodic increase of the upper and/or lower margin of the trace on aEEG without showing seizure activities on conventional EEG (CEEG). RESULTS: Of the 46 infants, 6 (13%) had the PST pattern. The PST pattern appeared following a flat trace or a continuous low-voltage pattern and was followed by a burst-suppression pattern. On CEEG, the PST pattern consists of alternating cycles of low-voltage irregular activities and almost flat tracing. The PST pattern was associated with neuroimaging abnormalities and with various degrees of neurodevelopmental outcomes. Positive predictive values of the PST or worse pattern for adverse outcomes were high at 12 h after birth. CONCLUSION: A novel aEEG background pattern in infants with HIE was reported. The PST pattern likely indicates a suppressed background pattern and may be linked to unfavorable outcomes. Further multicenter validation study is needed to clarify its clinical significance.