Acute and Postacute Clinical Characteristics of Coronavirus Disease 2019 in Children in Japan.

BACKGROUND: The clinical features of coronavirus disease 2019 (COVID-19) in children have been changing because of the emergence and rapid spread of variants of concern (VOC). The increase in cases infected with VOC has brought concern with persistent symptoms after COVID-19 in children. This survey aimed to analyze the clinical manifestations and persistent symptoms of pediatric COVID-19 cases in Japan. METHODS: We analyzed the clinical manifestations of pediatric COVID-19 cases reported between February 2020 and April 2022 in Japan, using a dedicated database updated voluntarily by the members of the Japan Pediatric Society. Using the same database, we also analyzed persistent symptoms after COVID-19 in children who were diagnosed between February 2020 and November 2021. RESULTS: A total of 5411 and 1697 pediatric COVID-19 cases were included for analyzing clinical manifestations and persistent symptoms, respectively. During the Omicron variant predominant period, the percentage of patients with seizures increased to 13.4% and 7.4% in patient groups 1-4 and 5-11 years of age, respectively, compared with the pre-Delta (1.3%, 0.4%) or Delta period (3.1%, 0.0%). Persistent and present symptoms after 28 days of COVID-19 onset were reported in 55 (3.2%). CONCLUSIONS: Our survey showed that the rate of symptomatic pediatric COVID-19 cases increased gradually, especially during the Omicron variant predominant period, and a certain percentage of pediatric cases had persistent symptoms. Certain percentages of pediatric COVID-19 patients had severe complications or prolonged symptoms. Further studies are needed to follow such patients.

Change Over Time in Seasonality and Severity of Children Hospitalized With Respiratory Syncytial Virus Infection in Japan.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis, and in temperate climates, late fall and winter epidemics of bronchiolitis are usually linked to RSV. In recent years in Japan, the RSV infection epidemic has occurred earlier, even during the hot season. This study aimed to evaluate the seasonal variation of RSV-associated hospitalizations over the past decade and the relationship between season and disease severity. METHODS: This was a retrospective single-center study. Hospitalized children were studied between 2011 and 2019. RSV was detected using rapid antigen detection tests. Clinical information was obtained from medical records, and patients were classified by 4 seasons of admission and analyzed for changes over time. RESULTS: Among 3750 children, 945 (25.2%) were RSV-positive. The seasonal proportion of hospitalized children who are RSV-positive showed a peak shift towards summer, with a turning point in 2016. Comparing 2011-2012 and 2018-2019, incidence increased from 6.8% to 46.3% during summer, whereas during fall decreased from 50.0% to 20.7% and decreased from 28.4% to 20.7% during winter ( P < 0.05). A similar trend was observed in the number of children requiring oxygenation in the earlier period; however, after the transition, there was no significant difference between seasons. CONCLUSIONS: Our findings showed that the RSV epidemic shifted to peak during summer until 2016. There was an association between seasonality and severity, such that many younger children were hospitalized during the autumn and winter and required more oxygen; however, after 2016, this difference was no longer observed.

The clinical characteristics of pediatric coronavirus disease 2019 in 2020 in Japan.

BACKGROUND: The COVID-19 pandemic has affected the lives of people of all ages. Most reports on pediatric cases suggest that children experience fewer and milder symptoms than do adults. This is the first nationwide study in Japan focusing on pediatric cases reported by pediatricians, including cases with no or mild symptoms. METHODS: We analyzed the epidemiological and clinical characteristics and transmission patterns of 840 pediatric (<16 years old) COVID-19 cases reported between February and December 2020 in Japan, using a dedicated database which was maintained voluntarily by members of the Japan Pediatric Society. RESULTS: Almost half of the patients (47.7%) were asymptomatic, while most of the others presented mild symptoms. At the time of admission or first outpatient clinic visit, 84.0% of the cases were afebrile (<37.5°C). In total, 609 cases (72.5%) were exposed to COVID-19-positive household members. We analyzed the influence of nationwide school closures that were introduced in March 2020 on COVID-19 transmission routes among children in Japan. Transmission within households occurred most frequently, with no significant difference between the periods before and after declaring nationwide school closures (70.9% and 74.5%, respectively). CONCLUSIONS: COVID-19 symptoms in children are less severe than those in adults. School closure appeared to have a limited effect on transmission. Controlling household transmission from adult family members is the most important measure for prevention of COVID-19 among children.

Outcomes in symptomatic preterm infants with postnatal cytomegalovirus infection.

Premature infants are at risk for developing symptomatic postnatal cytomegalovirus (CMV) disease, including sepsis-like syndrome. We performed a retrospective case-control study including infants born before 32 weeks of gestation and diagnosed with symptomatic postnatal CMV infection during the neonatal period. Neurodevelopmental outcome was evaluated using the Kyoto Scale of Psychological Development 2001 at 18 months of corrected age and at 3 years of age. Twenty-four infants were diagnosed with postnatal CMV infection; of them, 14 had sepsis-like symptoms and 10 had laboratory test abnormalities only. Home oxygen therapy was used significantly higher in the CMV-positive group compared with the control group at hospital discharge (52% vs 21%, P=0.032). The incidence of neurodevelopmental impairment was not significantly different between the two groups at 18 months of corrected age (29% vs 17%, P=0.48) and at 3 years of age (43% vs 29%, P=0.34). Postnatal CMV infection did not have a significant influence on neurodevelopmental outcomes of symptomatic preterm infants, although those in the CMV-positive group appeared worse. Larger studies with long-term follow-up are needed for a better understanding of continued neurodevelopmental outcomes in preterm infants with postnatal CMV infection.

A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study.

BACKGROUND: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. METHODS: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. FINDINGS: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0·02). INTERPRETATION: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. FUNDING: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship.

Effect of a vaccine information statement (VIS) on immunization status and parental knowledge, attitudes, and beliefs regarding infant immunization in Japan.

BACKGROUND: Because of the overabundance of vaccination information on the internet, in the media, and on social media, providing clear and correct information on immunization is critical for parental decision-making. In 2018, the Japan Pediatric Society created and distributed a Vaccine Information Statement (VIS) to provide appropriate immunization information to caregivers. The objectives of the present study were to evaluate the effect of the VIS on immunization rates, adherence to schedule, and parental understanding of immunization in Japan. METHODS: This cross-sectional study was conducted at 18 centers in 2 prefectures in Japan. Caregivers were assigned to an intervention group, which received the VIS and a questionnaire when their child reached the age of 1 month, and a control group, which received only the questionnaire. Using the self-reported questionnaires, we evaluated vaccination rates and schedule adherence at age 2 months, and parental knowledge, attitudes, and beliefs regarding immunization. Three months later, the questionnaires were returned, and the findings were compared between the 2 groups. RESULTS: We contacted 422 and 428 persons in the intervention and control groups, respectively, and 111/422 (26.3%) and 119/428 (27.8%) returned the surveys. Vaccination rates and adherence rates for the first dose of 4 recommended vaccines did not differ significantly (P > 0.25); however, there were some positive effects on items related to vaccine knowledge (P = 0.03), perceived benefits (P = 0.02), perceived barriers (P < 0.001), and perceived behavioral control (P = 0.01). CONCLUSION: The VIS improved parent comprehension of infant immunization. Future studies should examine if the effects of such an intervention persist and affect vaccine uptake throughout childhood.

Factors related to survival discharge in trisomy 18: A retrospective multicenter study.

Infants with trisomy 18 (T18) previously had a poor prognosis; however, the intensive care of these patients has markedly diversified the prognosis. We investigated the current situation of patients with T18, clarified factors for survival discharge, and surveyed actual home healthcare. A total of 117 patients with T18 admitted to nine institutions between 2000 and 2015 were retrospectively investigated. After excluding four patients whose outcomes were unclear, we divided 113 patients into two groups-the survival discharge group (n = 52) and the death discharge group (n = 61)-and compared maternal factors, perinatal factors, neonatal factors, and therapeutic factors between the groups. In addition, home healthcare, readmission, utilization of respite care and home nursing, and cause of death among the survival group were surveyed. Fifty-two (44%) patients with T18 survived at discharge and their 1-year survival rate was 29%. The survival group had a longer gestation period, larger physique, and longer survival time, compared to the death group. Independent factors associated with survival discharge were the absence of an extremely low birthweight infant (ELBWI), the absence of esophageal atresia and patent ductus arteriosus, and cardiovascular surgery. All surviving patients required some home healthcare. The most frequent cause of death was a respiratory disorder. We recommend discussing the treatment strategy with families in the presence of neonatologists or pediatric surgeons, who can explain differences in prognosis, based on the gestation period, birthweight, severity of cardiovascular disease, and cardiovascular surgery.

Standardization of nitric oxide inhalation in extremely preterm infants in Japan.

BACKGROUND: In perinatal medicine, inhaled nitric oxide (iNO) has been an important tool for the treatment of full-term and late-preterm infants with persistent pulmonary hypertension of the newborn (PPHN) and hypoxemic respiratory failure (HRF). Its use in more premature infants, however, is controversial. To evaluate the current clinical practices regarding use of acute iNO in extremely preterm infants, a nationwide survey was conducted in Japan. METHODS: A questionnaire survey was conducted from May to September, 2015. Questionnaires about PPHN and iNO treatment were sent to the doctor in charge of the neonatal care unit in 213 perinatal medical centers (PMC) that possessed iNO equipment in Japan. RESULTS: A total of 143 of the 213 PMC provided responses (67.1%). A diagnosis of PPHN was made exclusively on echocardiography in all PMC. On definitive PPHN diagnosis, iNO was selected in the majority of the PMC (72%) and started from ≤10 p.p.m. in most PMC (49.7%) for extremely preterm infants. During iNO therapy, cardiac function was checked on echocardiography by a neonatologist every ≤8 h. iNO weaning was started when differential peripheral oxygen saturation (SpO2 ) disappeared, or when SpO2 reached 100% and so on. After iNO concentration reached 5 p.p.m., it was decreased gradually and carefully in five steps, taking 12-24 h to go from 5 to 0 p.p.m. CONCLUSIONS: Inhaled nitric oxide was predominantly used in extremely preterm infants as early rescue therapy for PPHN based on echocardiography performed by a neonatologist.

MIRAGE syndrome is a rare cause of 46,XY DSD born SGA without adrenal insufficiency.

BACKGROUND: MIRAGE syndrome, a congenital multisystem disorder due to pathogenic SAMD9 variants, describes a constellation of clinical features including 46,XY disorders of sex development (DSD), small for gestational age (SGA) and adrenal insufficiency (AI). It is poorly understood whether SAMD9 variants underlie 46,XY DSD patients born SGA (46,XY DSD SGA) without AI. This study aimed to define the frequency and phenotype of SAMD9 variants in 46,XY DSD SGA without AI. METHODS: Forty-nine Japanese patients with 46,XY DSD SGA (Quigley scale, 2 to 6; gestational age-matched birth weight percentile, <10) without history of AI were enrolled. The single coding exon of SAMD9 was PCR-amplified and sequenced for each patient. Pathogenicity of an identified variant was verified in vitro. Placenta tissues were obtained from the variant-carrying patient, as well as from another previously described patient, and were analyzed histologically. RESULTS: In one 46,XY DSD SGA patient, a novel heterozygous SAMD9 variant, p.Phe1017Val, was identified. Pathogenicity of the mutant was experimentally confirmed. In addition to DSD and SGA, the patient had neonatal thrombocytopenia, severe postnatal grow restriction, chronic diarrhea and susceptibility to infection, all features consistent with MIRAGE, leading to premature death at age 14 months. The patient did not have any manifestations or laboratory findings suggesting AI. Placenta tissues of the two variant-carrying patients were characterized by maldevelopment of distal villi without other findings of maternal underperfusion. CONCLUSIONS: MIRAGE syndrome is a rare cause of 46,XY DSD SGA without AI. This study exemplifies that AI is a common feature of MIRAGE syndrome but that the absence of AI should not rule out a diagnosis of the syndrome.

Factors related to home health-care transition in trisomy 13.

Trisomy 13 (T13) is accompanied by severe complications, and it can be challenging to achieve long-term survival without aggressive treatment. However, recently, some patients with T13 have been receiving home care. We conducted this study to investigate factors related to home health-care transition for patients with T13.We studied 28 patients with T13 born between January 2000 and December 2014. We retrospectively compared nine home care transition patients (the home care group) and 19 patients that died during hospitalization (the discharge at death group). The median gestational age of the patients was 36.6 weeks, with a median birth weight of 2,047 g. Currently, three patients (11%) have survived, and 25 (89%) have died. The home care group exhibited a significantly longer gestational age (38.9 vs. 36.3 weeks, p = 0.039) and significantly larger occipitofrontal circumference Z score (-0.04 vs. -0.09, p = 0.019). Congenital heart defects (CHD) was more frequent in the discharge at death group, with six patients in the home care group and 18 patients in the discharge at death group (67% vs. 95%, p = 0.047), respectively. Survival time was significantly longer in the home care group than in the discharge at death group (171 vs. 19 days, p = 0.012). This study has shown that gestational age, occipitofrontal circumference Z score at birth, and the presence of CHD are helpful prognostic factors for determining treatment strategy in patients with T13.

Effects of the early administration of sivelestat sodium on bronchopulmonary dysplasia in infants: A retrospective cohort study.

BACKGROUND: Chorioamnionitis, or infiltration of the chorioamnion by neutrophils, is a risk factor associated with the development of bronchopulmonary dysplasia. Increased neutrophil elastase levels are observed in the tracheal aspirates of these patients. AIMS: To examine the effects of early administration of the selective neutrophil elastase inhibitor sivelestat, which is used to treat acute lung injury in adults, on bronchopulmonary dysplasia in extremely premature infants. STUDY DESIGN: Retrospective cohort study. SUBJECTS: This study included extremely low-birth-weight infants born at a gestational age<28weeks. Patients were divided into groups based on the receipt of sivelestat. OUTCOME MEASURES: The primary outcome was the rate of bronchopulmonary dysplasia-free survival at a postmenstrual age of 36weeks, and the secondary outcomes included various clinically significant factors of neonatal mortality and morbidity and adverse events. RESULTS: Of the 1031 included neonates, 124 (12.0%) were treated with sivelestat. Significant differences between the groups were noted for gestational age, delivery method, fetal number, the frequency of chorioamnionitis, immunoglobulin M levels, and WBC counts. No differences were identified concerning the bronchopulmonary dysplasia-free survival rate at a postmenstrual age of 36weeks (adjusted odds ratio for sivelestat to control, 0.83; 95% confidence interval=0.53-1.30). Secondary outcomes did not significantly differ between the groups. CONCLUSIONS: In extremely premature infants, early sivelestat use was not associated with an improved rate of survival without bronchopulmonary dysplasia at a postmenstrual age of 36weeks.

Prognostic factors of hydrops fetalis with pleural effusion.

BACKGROUND: Hydrops fetalis (HF) has a low survival rate, particularly in the case of preterm birth. In addition, the severity index of HF has not been fully investigated yet. The aim of this study was to clarify the prognostic factors of HF with pleural effusion. METHODS: All live-born HF patients with pleural effusion, except for chromosomal abnormality or complex congenital heart disease, born from 2009 to 2013 in Aichi Prefecture in Japan were included. Prenatal, perinatal, and postnatal information was obtained from the medical records and was retrospectively analyzed. RESULTS: Forty-one HF patients with pleural effusion were included, and 28 patients (68%) survived. On multivariate logistic stepwise analysis, gestational birth week (OR, 0.71; 95% CI: 0.52-0.96, P = 0.027) and standard deviation (SD) score of the birthweight (OR, 1.74; 95% CI: 1.01-2.99, P = 0.045) were significant factors for postnatal death. All patients with both ≥32 gestational weeks and <3.0 birthweight SD score survived. CONCLUSIONS: Combined with the gestational weeks data, birthweight SD score may be useful to estimate the prognosis of HF with pleural effusion.

Outcome in VLBW infants with surgical intestinal disorder at 18 months of corrected age.

BACKGROUND: Surgical intestinal disorders, such as necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and meconium-related ileus (MRI), are serious morbidities in very low-birthweight infants (VLBWI). The aim of this study was to compare the composite outcomes of death or neurodevelopmental impairment (NDI) in VLBWI with surgical intestinal disorders and assess independent risk factors for death and NDI at 18 months of corrected age. METHODS: A retrospective matched-cohort study was conducted at 11 institutes. We included VLBWI who had undergone laparotomy for NEC, FIP, and MRI. Two control subjects were chosen for every surgical patient and matched for gestational age and birthweight to form the comparison group. Death and neurodevelopmental outcome at 18 months of corrected age were evaluated. RESULTS: The number of infants in the NEC, FIP, MRI, and control groups was 44, 47, 42, and 261, respectively. In-hospital mortality was higher in infants with NEC and MRI relative to those in the control group (P < 0.001). The incidence rate for NDI at 18 months of corrected age was higher in infants with MRI relative to those in the control group (P = 0.021). On logistic regression analysis, low gestational age, male sex, small for gestational age, intraventricular hemorrhage, and MRI were associated with increased risk of death or NDI at 18 months of corrected age. CONCLUSIONS: NEC and MRI were associated with in-hospital mortality, and MRI was associated with NDI or death at 18 months of corrected age.

Differences between periventricular hemorrhagic infarction and periventricular leukomalacia.

PURPOSE: To clarify the differences between infants with periventricular hemorrhagic infarction (PVHI) and those with periventricular leukomalacia (PVL). METHODS: We retrospectively evaluated the clinical features, ultrasonography, and electroencephalogram (EEG) findings in 22 preterm infants with PVHI and 49 with PVL. EEG and cranial ultrasonography were serially performed in all participants starting immediately after birth. Acute and chronic stage EEG abnormalities were evaluated separately. RESULTS: Gestational age and birth weight were significantly lower in infants with PVHI than those with PVL. EEGs were normal in the majority of infants with PVHI on days 1-2. However, EEG abnormalities appeared after ultrasonography abnormalities. The majority of infants with PVL showed acute-stage EEG abnormalities on days 1-2. The rate of infants with acute-stage EEG abnormalities decreased with age, whereas the rate of infants with chronic-stage EEG abnormalities increased with age. Normal EEG before ultrasonography abnormalities was more common in infants with PVHI than in those with PVL. However, deterioration of acute-stage EEG abnormalities was more frequent in infants with PVHI than in those with PVL. CONCLUSIONS: PVHI was presumed to cause mostly postnatal injury, whereas PVL was presumed to cause mostly pre-or perinatal injury.

MBTPS2 mutation causes BRESEK/BRESHECK syndrome.

BRESEK/BRESHECK syndrome is a multiple congenital malformation characterized by brain anomalies, intellectual disability, ectodermal dysplasia, skeletal deformities, ear or eye anomalies, and renal anomalies or small kidneys, with or without Hirschsprung disease and cleft palate or cryptorchidism. This syndrome has only been reported in three male patients. Here, we report on the fourth male patient presenting with brain anomaly, intellectual disability, growth retardation, ectodermal dysplasia, vertebral (skeletal) anomaly, Hirschsprung disease, low-set and large ears, cryptorchidism, and small kidneys. These manifestations fulfill the clinical diagnostic criteria of BRESHECK syndrome. Since all patients with BRESEK/BRESHECK syndrome are male, and X-linked syndrome of ichthyosis follicularis with atrichia and photophobia is sometimes associated with several features of BRESEK/BRESHECK syndrome such as intellectual disability, vertebral and renal anomalies, and Hirschsprung disease, we analyzed the causal gene of ichthyosis follicularis with atrichia and photophobia syndrome, MBTPS2, in the present patient and identified an p.Arg429His mutation. This mutation has been reported to cause the most severe type of ichthyosis follicularis with atrichia and photophobia syndrome, including neonatal and infantile death. These results demonstrate that the p.Arg429His mutation in MBTPS2 causes BRESEK/BRESHECK syndrome.

Nationwide surveillance of circulatory collapse associated with levothyroxine administration in very-low-birthweight infants in Japan.

BACKGROUND: Although the administration of levothyroxine sodium (LT4) to premature infants had been considered safe, several cases of late-onset circulatory collapse (LCC) following the administration of LT4 in very-low-birth-weight (VLBW) infants have been reported in Japan since 2008. This study was performed to investigate the incidence of LCC associated with the administration of LT4 to VLBW infants. METHODS: A questionnaire regarding LCC with or without an association with LT4 administration in VLBW infants from 2006 to 2008, was sent to 212 hospitals belonging to the Japan Neonatologist Association. RESULTS: Data of 8727 VLBW infants were analyzed, and 46 cases of LCC associated with the administration of LT4 were reported in this surveillance. Especially, an analysis for infants weighing between 1000 and 1499 g at birth revealed that the incidence of LCC with the administration of LT4 was higher than that of those without LT4. CONCLUSIONS: LT4 is widely used for infants, including VLBW infants, and no major complications have been reported. However, our study revealed that more than a few cases of LCC were associated with the administration of LT4 in VLBW infants. In conclusion, careful attention is necessary when initiating the administration of LT4 to VLBW infants.

Prolonged EEG depression in term and near-term infants with hypoxic ischemic encephalopathy and later development of West syndrome.

PURPOSE: This study was performed to clarify the relationship between prolonged depression of electroencephalography (EEG) in term and near-term infants with hypoxic ischemic encephalopathy (HIE) and the later development of West syndrome (WS). METHODS: We investigated 17 term and near-term infants with HIE. Inclusion criteria were as follows: ≥35 weeks of gestation, clinical signs of HIE, magnetic resonance imaging (MRI) lesions corresponding to HIE, assessment of outcome at >18 months of age, depression of EEG, and serial EEG examinations. The 17 infants were divided into the following two groups: Group A (n = 4) with prolonged EEG depression over 21 days of age, and group B (n = 13) with disappearance of EEG depression by 21 days of age. RESULTS: WS developed in all four infants in group A, but in only one of 13 infants in group B. WS occurred significantly more frequently in group A than in group B. For the prediction of subsequent development of WS, prolonged EEG depression over 21 days of age showed sensitivity of 0.80 and specificity of 1.0. In both groups, abnormal irregular faster waves with or without EEG depression were seen in 11 infants between 2 and 28 days of age. They had no significant relationship with WS, but were significantly related to an adverse developmental outcome. CONCLUSIONS: Prolonged depression of EEG over 21 days of age in term or near-term infants with HIE is a valuable predictor of the later development of WS.

Nutritional state, maturational delay on electroencephalogram, and developmental outcome in extremely low birth weight infants.

The aim of this study is to clarify the relation among developmental outcome, nutritional state during the neonatal period, maturational electroencephalographic changes. Thirteen extremely low birth weight infants who completed 6- or 9-year follow-up were a subject of this study. Undernutrition was defined as enteral feeding below 100mL/kg/day at 3 weeks of age. Dysmature patterns were defined as the persistence of EEG patterns 2 weeks or more immature for post-conceptional age. IQ was examined at 6 and 9 years of age. Body height and weight, and head circumference at 6 years of age were stratified by the percentile grades. Full and verbal IQ was significantly lower in infants with undernutrition than those with normal nutrition. Among infants with undernutrition, those with persistent dysmature patterns tended to have lower full and performance IQ than those without persistent dysmature patterns. Head circumference was 50 percentile or larger in all infants with normal nutrition, whereas it was below 50 percentile in six of eight infants with undernutrition. Extremely low birth weight infants with undernutrition had worse neurodevelopmental outcome at 6 or 9 years of age than those with normal nutrition. Among infants with undernutrition, developmental outcome was relatively worse in those with persistent dysmature patterns than those without.

Delayed neurological signs following isolated parasagittal injury in asphyxia at term.

BACKGROUND: Parasagittal cerebral injury is a type of cerebral injury in term infants, which is characterized by the predominant injury of the arterial border zones of the anterior, middle and posterior cerebral arteries, however its early clinical manifestation is mostly unclear. AIM: To understand early clinical features of parasagittal cerebral injury. METHODS: The clinical details of 18 newborn infants who were diagnosed as having parasagittal cerebral injury on magnetic resonance imaging (MRI). Eleven infants had localized injury within parasagittal regions ("Limited" group), 7 infants had diffuse extensive injury involving the deep gray matter and/or periventricular white matter ("Extensive" group). These infants were compared with 9 infants with perinatal asphyxia without MRI abnormalities ("Normal" group). RESULTS: There was no significant difference in the rate of cardiotocographic abnormalities, low Apgar scores, low blood pH and base excess, and the requirement for mechanical ventilation among three groups. Compared with the Normal group, fewer infants in the Limited group developed neonatal encephalopathy within an hour after birth. Neonatal seizures were more frequent in the Limited and the Extensive groups. Hepatic and/or renal dysfunction was more often observed in the Limited group. Cerebral palsy and/or mental retardation were common in the Extensive group. Electro-cortical depression was more in the Extensive group. Progressive suppression of electro-cortical activity was common within infants in the Limited group (33%) and the Extensive group (60%). CONCLUSION: Infants with parasagittal cerebral injury developed serious neurological abnormalities despite less serious physiological and neurological manifestation shortly after birth, suggesting the importance of careful longitudinal observation of asphyxiated infants.

Aplasia cutis congenita with skull defect in a monozygotic twin after exposure to methimazole in utero.

BACKGROUND: Aplasia cutis congenita (ACC) is a condition in which localized or widespread areas of skin are absent at birth. Defective lesions show complete absence of all layers of skin, occasionally extending to skull or dura. ACC is etiologically heterogeneous; many different etiologies including teratogens have been documented. CASE: We describe the first reported case of a monozygotic twin with ACC after exposure to methimazole in utero. The female patient was born at 36 weeks gestation as the first child of monozygotic twins. The mother received methimazole between the 11th and 17th weeks of pregnancy because of transient hyperthyroidism. The second child did not have ACC. The patient had defects of the scalp, skull, and dura (7 x 5 cm) on the sagittal line of the parieto-occipital region. No other malformations were noted. The scalp defect has been treated daily with sterile physiological saline and petrolatum dressing in addition to intravenous antibiotics. Trafermin, a recombinant human fibroblast growth factor, was sprayed from day 6 to promote epithelialization of the scalp defect. On day 21, she had high fever due to infection of the defect lesion, which was controlled by povidone iodine dressing and intravenous antibiotics. The defect of the scalp was well healed after 6 weeks, but the skull defect remained unclosed. CONCLUSIONS: We describe a rare case of a monozygotic twin with ACC and skull defect after methimazole exposure in utero. The findings of our case suggest that methimazole is a potential teratogen of ACC.