Birth weight, Apgar scores and gentamicin were associated with acute kidney injuries in VLBW neonates requiring treatment for patent ductus arteriosus.

AIM: We assessed the risk factors for transient acute kidney injury in very low birth weight (VLBW) infants treated for patent ductus arteriosus (PDA) using the serum creatinine-based criteria in Kidney Disease: Improving Global Outcomes. METHOD: This retrospective study of infants requiring ibuprofen and, or, surgery for haemodynamic relevant PDAs was performed at the University Children's Hospital of Saarland, Homburg, Germany, from January 2009 to December 2015. RESULTS: We studied 422 infants with a mean birth weight of 1059 ± 308.2 g. Acute kidney injuries developed in 150/295 infants (50.9%) with spontaneous PDA closure, in 46/82 (56.1%) who received intravenous ibuprofen treatment, in 18/24 (75.0%) who had surgery and in 15/21 infants (71.4%) who received both medical and surgical treatment. Acute kidney injuries were associated with birth weight and gestational age, Apgar scores at 10 minutes, the PDA size corrected for birth weight, a PDA with three affected circulatory territories, PDA surgery and gentamicin. Multiple logistic regression analysis showed particular associations between acute kidney injury and birth weight (p = 0.001), the 10-minute Apgar score (p = 0.02) and gentamicin (p = 0.043). CONCLUSION: Birth weight, the 10-minute Apgar score and gentamicin were particularly associated with acute kidney injuries in our cohort.

[Parenteral nutrition in premature babies with a birth weight <1500g: a systematic single-center analysis and comparison with current guidelines]. / Parenterale Ernährung bei Frühgeborenen mit einem Geburtsgewicht <1500 g: eine systematische Zentrumsanalyse und Vergleich mit publizierten Leitlinien.

BACKGROUND: Parenteral and enteral nutrition are essential for both growth and development of preterm infants. Based on the results of many studies, the rate of nutritional growth and the amount of substrate delivered parenterally are under debate. OBJECTIVE: The main aim of this study was to assess parenteral nutrition in very and extremely immature preterm infants, i.e. very low birth weight (VLBW, birth weight <1500g) and extremely low birth weight (ELBW, birth weight <1000g) neonates, and to compare the amount of parenterally delivered substrate in our neonatal intensive care unit (NICU) to current German guidelines. METHODS: Retrospective audit at our tertiary NICU at the University Children's Hospital of Saarland, Homburg, Germany between 1 January 2009 and 31 December 2010. RESULTS: In total, 100 premature neonates were included. The mean gestational age was 29.6 weeks (range 24.4-34.1 weeks) and the mean birth weight was 1119 g ± 260 g (range 570 g-1490 g). Comparing the amount of fluids, glucose, amino acids, lipids and kcals with the current guidelines of the German Society for Nutritional Medicine in preterm infants, only glucose was adequately given; however, a substantial number of weight-dependent (more often in ELBW neonates) episodes of hyperglycemia requiring insulin treatment were also seen. During the first 3 weeks of life a substantial drop in body weight, length and head circumference occurred in our study cohort. In contrast, at 2 years corrected age, catch-up growth was seen in our cohort with anthropometric data now comparable to healthy term infants. Using the Bayley II test for developmental outcome assessment, at 2 years corrected age 78.6% (33/42) of infants demonstrated normal development. CONCLUSIONS: This retrospective data analysis demonstrated inadequate provision of parenteral nutrition in our NICU, which was often not in line with current German guidelines. This was associated with inadequate growth in our cohort, most notably during the first 3 weeks of life; however, implementation of current guidelines is impeded by metabolic disturbances in this cohort, most notably in ELBW neonates. Whether adherence to published guidelines will result in better early ex utero growth, and whether this normalized growth pattern will translate into better long-term outcome on a metabolic and neurological level, remains unclear.

Low breastfeeding continuation to 6 months for very preterm infants: A European multiregional cohort study.

Breastfeeding confers multiple benefits for the health and development of very preterm infants, but there is scarce information on the duration of breastfeeding after discharge from the neonatal intensive care unit (NICU). We used data from the Effective Perinatal Intensive Care in Europe population-based cohort of births below 32 weeks of gestation in 11 European countries in 2011-2012 to investigate breastfeeding continuation until 6 months. Clinical and sociodemographic characteristics were collected from obstetric and neonatal medical records as well as parental questionnaires at 2 years of corrected age. Among 3,217 ever-breastfed infants, 34% were breastfeeding at 6 months of age (range across countries from 25% to 56%); younger and less educated mothers were more likely to stop before 6 months (adjusted relative risk [aRR] <25 years: 0.68, 95% CI [0.53, 0.88], vs. 25-34 years; lower secondary: 0.58, 95% CI [0.45, 0.76] vs. postgraduate education). Multiple birth, bronchopulmonary dysplasia (BPD), and several neonatal transfers reduced the probability of continuation but not low gestational age, fetal growth restriction, congenital anomalies, or severe neonatal morbidities. Among infants breastfeeding at discharge, mixed versus exclusive breast milk feeding at discharge was associated with stopping before 6 months: aRR = 0.60, 95% CI [0.48, 0.74]. Low breastfeeding continuation rates in this high-risk population call for more support to breastfeeding mothers during and after the neonatal hospitalization, especially for families with low socio-economic status, multiples, and infants with BPD. Promotion of exclusive breastfeeding in the NICU may constitute a lever for improving breastfeeding continuation after discharge.

Diagnosis and Treatment of Tuberous Sclerosis Manifestations in Children: A Multicenter Study.

Tuberous sclerosis complex (TSC) is a genetic disease with a significant morbidity and mortality. We conducted a retrospective analysis of two cohorts (Vall d'Hebron University Hospital [HVH], Barcelona, Spain, 1982-2015, and at Saarland University Medical Center [UKS], Homburg, Germany, 1998-2015) to assess prevalence and treatment of TSC associated manifestations and to evaluate if the follow-up was in line with published recommendations. This was considered if more than 15% of patients did not receive adequate examination with regard to potential organ involvement. A definite diagnosis was made in 52 patients (96%), and a possible diagnosis was made in 2 patients (4%). Thirty-four (63%) patients were from HVH and 20 (37%) from UKS. Median age at first presentation was 6 months (interquartile range: 0-38 months), and median time of follow-up was 6 years (interquartile range: 2-13 years). Clinical symptoms that led to a diagnosis of TSC were cardiac rhabdomyoma (22/54), epilepsy (20/54), and cutaneous manifestations (4/54). Assessment of neuropsychiatric, renal, and ocular manifestations was inadequate in both hospitals, whereas cutaneous manifestation was inadequate at UKS only. Our data demonstrate insufficient examinations in a substantial number of TSC patients with regard to neuropsychiatric, renal, ocular, and cutaneous manifestations. The recently published guidelines may prove valuable in establishing a more comprehensive approach.

Review demonstrates that less invasive surfactant administration in preterm neonates leads to fewer complications.

Surfactant treatment of neonatal respiratory distress syndrome (RDS) was introduced in Europe during the 1990s. Meta-analyses have indicated that using less invasive surfactant administration techniques on preterm neonates receiving continuous positive airway pressure (CPAP) results in improved survival rates without bronchopulmonary dysplasia. Surfactant should be administered early and ventilator settings adapted to changing oxygen requirements and lung mechanics. Side effects including initial bradycardia, oxygen desaturation, tube obstruction and isolated cases of pulmonary haemorrhage have been reported. CONCLUSION: Less invasive surfactant therapy improves pulmonary outcomes in preterm neonates with RDS and should ideally be administered in combination with CPAP.

[Long-term Outcome after Prenatal Drug Exposure]. / Langzeitkonsequenzen der intrauterinen Drogenexposition.

Although prenatal exposure to opioids, cannabinoids and cocaine is a frequent problem, only scarce data have been published on the long-term outcome in affected children and adolescents. While opioid-exposed children up to the age of 2 years show a reduced motor developmental pattern, data from meta-analyses up to adolescence show a strong trend for reduced performance with regard to cognitive function and behavior. Follow-up data after intrauterine cannabinoid exposure indicate reduced cognitive and reading abilities as well as abnormal findings in complex planning tests. Externalizing pathologies have been observed more frequently in boys. Prenatal cocaine exposure results in reduced cognitive and verbal development up to adolescence; however, differences are small but significant in meta-analyses. Interpretation of follow-up data with partially contradictory results may reflect methodological differences and a number of modifying co-factors, e.g., social conditions during the childhood period. These data should encourage further primary and secondary preventive attempts.

Quantitative, Phenotypical, and Functional Characterization of Cellular Immunity in Children and Adolescents With Down Syndrome.

Background: Infections and autoimmune disorders are more frequent in Down syndrome, suggesting abnormality of adaptive immunity. Although the role of B cells and antibodies is well characterized, knowledge regarding T cells is limited. Methods: Lymphocyte subpopulations of 40 children and adolescents with Down syndrome and 51 controls were quantified, and phenotype and functionality of antigen-specific effector T cells were analyzed with flow cytometry after polyclonal and pathogen-specific stimulation (with varicella-zoster virus [VZV] and cytomegalovirus [CMV]). Results were correlated with immunoglobulin (Ig) G responses. Results: Apart from general alterations in the percentage of lymphocytes, regulatory T cells, and T-helper 1 and 17 cells, all major T-cell subpopulations showed higher expression of the inhibitory receptor PD-1. Polyclonally stimulated effector CD4+ T-cell frequencies were significantly higher in subjects with Down syndrome, whereas their inhibitory receptor expression (programmed cell death 1 [PD-1] and cytotoxic T-lymphocyte antigen 4 [CTLA-4]) was similar to that of controls and cytokine expression profiles were only marginally altered. Pathogen-specific immunity showed age-appropriate levels of endemic infection, with correlation of CMV-specific cellular and humoral immunity in all subjects. Among VZV IgG-positive individuals, a higher percentage of VZV-specific T-cell-positive subjects was seen in those with Down syndrome. Conclusions: Despite alterations in lymphocyte subpopulations, individuals with Down syndrome can mount effector T-cell responses with similar phenotype and functionality as controls but may require higher effector T-cell frequencies to ensure pathogen control.

Variation in term birthweight across European countries affects the prevalence of small for gestational age among very preterm infants.

AIM: This study assessed the prevalence of small for gestational age (SGA) among very preterm (VPT) infants using national and European intrauterine references. METHODS: We generated country-specific and common European intrauterine growth references for 11 European countries, according to Gardosi's approach and Hadlock's foetal growth model, using national data on birthweights by sex. These references were applied to the Effective Perinatal Intensive Care in Europe (EPICE) cohort, which comprised 7766 live VPT births without severe congenital anomalies under 32 weeks of gestation in 2011-2012, to estimate the prevalence of infants with SGA birthweights, namely those below the 10th percentile. RESULTS: The SGA prevalence was 31.8% with country-specific references and 34.0% with common European references. The European references yielded a 10-point difference in the SGA prevalence between countries with lower term birthweights (39.9%) - Portugal, Italy and France - and higher term birthweights, namely Denmark, the Netherlands, Sweden (28.9%; p < 0.001). This was not observed with country-specific references, where the respective figures were 32.4% and 33.9% (p = 0.34), respectively. CONCLUSION: One-third of VPT infants were SGA according to intrauterine references. Common European references showed significant differences in SGA prevalence between countries with high and low-term birthweights.

Are Cytokines Useful Biomarkers to Determine Disease Severity in Neonates with Congenital Diaphragmatic Hernia?

Background This study investigates plasma cytokine levels in neonates with the more common left-sided congenital diaphragmatic hernia (CDH) and correlates them with severity of disease indicated by position of the liver. An intrathoracic part of liver is associated with higher need for extracorporeal membrane oxygenation (ECMO) and higher risk for chronic lung disease (CLD). Methods A total of 28 newborns with CDH were subdivided by their liver position in partially intrathoracic (n = 16) and only abdominal (n = 12) position. Only liver-up patients went on ECMO (n = 9) and developed severe/moderate CLD (n = 5). Controls consisted of 19 healthy matched-term neonates. Laboratory samples were extracted from umbilical cord blood and during the neonatal period. Results In umbilical cord blood, CDH patients showed decreased IL-8 values while MIP-1a (macrophage inflammatory protein-1) values were increased. Concerning the severity of CDH, we measured significantly higher levels of TGFb2 in CDH patients with liver-up than in liver-down cases and controls (p < 0.006). During the neonatal period, the concentration of IL-10 and vascular endothelial growth factor (VEGF) showed significant deviations in the liver-up group with need for ECMO (p < 0.009). Conclusion In neonates with CDH, plasma cytokine levels are already altered in utero. TGFb2 may work as an early predictor for severity of disease. VEGF and IL-10 could serve as potential biomarkers predicting the course of disease in CDH.

Up-date on the NeoVitaA Trial: Obstacles, challenges, perspectives, and local experiences.

The aim of the NeoVitaA Trial is to assess the role of postnatal additional high-dose oral vitamin A supplementation for 28 days in reducing Bronchopulmonary dysplasia (BPD) or death in extremely low birth weight (ELBW) infants at 36 weeks postmenstrual age (PMA). All infants (both intervention and control group) will be provided with basic vitamin A (1000 IU/kg/day) in addition to trial intervention.In this short communication, we will give an up-date on obstacles, challenges as well as perspectives and potential solutions when putting into place a multicenter, double-blind, randomized trial in this cohort of extremely susceptible infants.

Episodes of hypo- and hypercapnia in a cohort of mechanically ventilated VLBW infants: the role of adequate staffing.

In preterm neonates, the use of invasive ventilation may be mandatory because of respiratory distress syndrome (RDS). In this short communication, we demonstrate that invasive ventilation in this susceptible cohort may be associated with episodes of both hypo- and hypercapnia, and that inadequate ventilatory support is associated with the occurrence rate of bronchopulmonary dysplasia (BPD; p < 0.05). Also, inadequate mechanical ventilation is aggravated by a shortage of medical staff.

The role of EEG recordings in children undergoing cardiac surgery for congenital heart disease.

BACKGROUND: Neurological dysfunction may occur after corrective cardiac surgery using cardio-pulmonary bypass (CPB) with or without circulatory arrest. Different neurophysiological monitoring systems have been employed to detect neurological complications and possible brain injury in infants and children during and after cardiac surgery. The value of Elecetroencephalogram (EEG) in infants and children at risk for neurological sequelae has not been systematically studied. METHODS: Sequential performance of two EEGs before and after cardiac surgery at a tertiary University Hospital to screen for possible brain injury after cardiac surgery in neonates and children undergoing CPB surgery. In addition, a complete neurological examination and assessment by a physiotherapist was performed. RESULTS: Over a 4-year period, in 313 patients (age: 54.2 ± 55.7 months; normal initial EEG) after cardiac surgery CPB (duration of surgery: 146.0 ± 58.9 min; aortic cross clamp time: 34.1 ± 19.1 min), a 19-channel EEG recording was performed 2.4 ± 1.8 days prior to and 11.6 ± 5.3 days after cardiac surgery. An abnormal EEG was detected in only 8 of 313 patients (2.5%; focal slowing: 1, generalised slowing: 5, epiletiform discharges: 2) after cardiac surgery, while the EEG was normal in the remaining 305 patients (97.5%). In 1 patient, an intra-cerebral pathology was seen on MRI (ischemic); in 5 patients, follow-up EEGs were performed, which revealed normalized findings. None of the 8 patients demonstrated new focal neurological deficits on physical examination, but 33 (9.7%) children demonstrated minor abnormalities (e.g., subtle motor asymmetry, increase in muscle tone, etc.), which were unrelated to abnormal EEG findings. CONCLUSIONS: According to the used protocol, pathological EEG findings were very infrequent in our study cohort. The routine and indiscriminative recording of EEGs in children before and after corrective or palliative cardiac surgery for congenital heart disease using CPB is not recommended. Further intra-operative neuromonitoring methods with immediate intervention should be evaluated.

Role of multiplex PCR analysis in children with febrile seizures.

BACKGROUND: The aim of this study was to assess multiplex PCR analysis in detecting causative viruses in children with febrile seizures. METHODS: The study was a retrospective analysis comparing data from a pre-multiplex era (2009) with a period after the introduction of routine respiratory multiplex analysis (2010-2013) in children with febrile seizures. RESULTS: We included 200 children with febrile seizures (mean age: 29.5 ± 1.4.months; 104 male) in the study. In 2009, in 10 out of 49 (20 %) children, microbiology testing (bacterial/fungal) was positive compared with a rate of 74 out of 151 (49 %) children during 2010-2013 (p < 0.01). The rate of positive virological studies increased from 10 (20 %) in 2009 to 73 (48.3 %) in the period 2010-2013 (p < 0.01). Multiplex PCR analysis confirmed viral infections in 52 of 73 cases (71.2 %). CONCLUSION: Routine multiplex PCR analysis fosters the detection of respiratory viruses in children with febrile seizure. The precise role of multiplex analysis in the management of these children awaits further clarification.

[ESPED-Survey: TSC-disease in children and adolescents: preliminary results from a German epidemiological survey]. / ESPED-Erhebung: TSC-Erkrankung bei Kindern und Jugendlichen: eine einjährige Interim-Analyse.

BACKGROUND: Tuberous sclerosis complex (TSC) disease is a rare genetic, multi-organ disorder characterized by the occurrence of multiple hamartoma. METHODS: In cooperation with ESPED, Germany, a prospective, epidemiological study was performed to assess the incidence of newly diagnosed TSC disease in patients ≤18 years in Germany. Moreover, the following parameters were assessed: 1. Age distribution at initial diagnosis; 2. Percentage of patients with in utero diagnosis of TSC; 3. Detailed description of pathological clinical findings; 4. Results from genetic testing. RESULTS: In this one-year interim analysis, 84 electronic questionnaires were received, 17 of which did not contain complete sets of data and were not included in data analysis. Twenty-three of 67 questionnaires did not report TSC patients and 3 reports contained redundant data sets and were excluded. In total, 41 reports were included into data analysis (female: 23; male: 18); median age at first diagnosis was 6 months (range: 0-151 months). The three most common symptoms were: central nervous affection: 31/41 patients ((75.6 %); 29/31 with seizures); rhabdomyoma: in 20/41 (48.8 %); cutaneous affection: hypomelanotic maculae ("white spots"): 20/41 (48.8 %). The three following organ manifestations were seen most often in a comprehensive diagnostic work-up: rhabdomyoma: 23/41 ((56.1 %); cortical dysplasia: 22/41 (53.7 %); "white spots"): 20/41 (48.8 %). In 11/41 patients, cardiac rhabdomyoma were detected by ultrasonography prenatally. In 6 patients, a TSC-2 mutation was found while in 4 patients a TSC-1 mutation was noted; in 1 patient, genetic testing was negative. CONCLUSIONS: Based on our preliminary findings, the annual incidence rate for TSC disease is estimated at approximately 1:12,300 live births, but this is a very rough approximation.

Risk Factors for Peri- and Intraventricular Hemorrhage in Very Preterm Neonates.

Peri- und intraventrikuläre Blutungen werden in der internationalen Literatur nach Papile LA in 4 Schweregrade klassifiziert 10. Obschon diese Klassifikation auf den zu diesem Zeitpunkt gebräuchlichen computertomografischen Befunden fußt, hat sie bis heute ihre Wertigkeit in der internationalen Literatur. Diese Blutungsentität bei sehr unreifen Frühgeborenen stellt sowohl für die akute Überlebensprognose als auch für die langfristige Entwicklung einer der wichtigsten Risikofaktoren dar. Zahlreiche klinische Kohortenstudien belegen die dargestellten Zusammenhänge bis in die aktuelle Literatur hinein bereits seit Dekaden 8. Daher war die Erfassung von Risikofaktoren und deren jeweilige Aktualisierung für entsprechende Behandlungsperioden eine Säule der neonatologischen Forschung. Diesem Thema widmet sich die in der aktuellen Ausgabe die Untersuchung an eine bundesdeutschen Kohorte aus Ulm 15.

Infectious and immunologic phenotype of MECP2 duplication syndrome.

MECP2 (methyl CpG binding protein 2) duplication causes syndromic intellectual disability. Patients often suffer from life-threatening infections, suggesting an additional immunodeficiency. We describe for the first time the detailed infectious and immunological phenotype of MECP2 duplication syndrome. 17/27 analyzed patients suffered from pneumonia, 5/27 from at least one episode of sepsis. Encapsulated bacteria (S.pneumoniae, H.influenzae) were frequently isolated. T-cell immunity showed no gross abnormalities in 14/14 patients and IFNy-secretion upon ConA-stimulation was not decreased in 6/7 patients. In 6/21 patients IgG2-deficiency was detected - in 4/21 patients accompanied by IgA-deficiency, 10/21 patients showed low antibody titers against pneumococci. Supra-normal IgG1-levels were detected in 11/21 patients and supra-normal IgG3-levels were seen in 8/21 patients - in 6 of the patients as combined elevation of IgG1 and IgG3. Three of the four patients with IgA/IgG2-deficiency developed multiple severe infections. Upon infections pronounced acute-phase responses were common: 7/10 patients showed CRP values above 200 mg/l. Our data for the first time show systematically that increased susceptibility to infections in MECP2 duplication syndrome is associated with IgA/IgG2-deficiency, low antibody titers against pneumococci and elevated acute-phase responses. So patients with MECP2 duplication syndrome and low IgA/IgG2 may benefit from prophylactic substitution of sIgA and IgG.

Modifications of recognition memory processes in preterm children: an event-related potential study.

Prematurity may cause hippocampal compromise. Therefore, hippocampus-dependent memory processes (recollection-based retrieval) may be more impaired than hippocampus-independent processes (familiarity-based retrieval). The memory of 18 children born preterm with reduced hippocampal volumes, without neonatal complications (weeks of gestation < 34, weight < 1,600 g), and 15 controls (8-10 years) was tested using an item recognition task. While groups were equal in memory performance, dissociation was found: The event-related potential (ERP) correlate of familiarity was intact in the preterm group, whereas the correlate of recollection was attenuated. A follow-up experiment ruled out that this was due to general cognitive deficits. Furthermore, gestational age correlated with the ERP index of recollection. Thus, recognition memory in preterm children may be characterized by a compensation of attenuated recollection by familiarity.

Clinical recommendations of Cochrane reviews in pediatric gastroenterology: systematic analysis.

BACKGROUND: Systematic and up-to-date Cochrane reviews in pediatrics in general and in pediatric gastroenterology in particular are important tools in disseminating the best available evidence to the medical community, thus providing the physician at the bedside with invaluable information and recommendations with regard to specific clinical questions. METHODS: A systematic literature review was conducted, including all Cochrane reviews published by the Cochrane Review Group in the field of pediatric gastroenterology between 1993 and 2012, with regard to the percentage of reviews that concluded that a certain intervention provided a benefit, percentage of reviews that concluded that a certain intervention should not be performed, and percentage of studies that concluded that the current level of evidence was inconclusive. RESULTS: In total, 86 reviews in the field of pediatric gastroenterology were included. The majority of reviews assessed pharmacological interventions (46/86); other important fields included prevention (15/86) and nutrition (9/86). A total of 33/86 reviews issued definite recommendations (positive, 19/86; negative, 14/86). The remaining 53/86 reviews were either inconclusive (24/86) or only of limited conclusiveness (29/86). The percentage of inconclusive reviews increased from 9% (1998-2002) to 19% (2003-2007; P < 0.05) to finally 24% (2008-2012) (P < 0.05). The three most common reasons for the need for further research were heterogeneity of studies (26/86), small number of patients (18/86), and insufficient data (16/86). CONCLUSIONS: Further high-quality research is necessary to increase the proportion of reviews with clear recommendations. Funding and research agencies are key to selecting the most appropriate research programs.

Severe cyanide poisoning from an alternative medicine treatment with amygdalin and apricot kernels in a 4-year-old child.

BACKGROUND: The use of complementary and alternative medicine (CAM) is widespread in children with cancer and is poorly regulated. PATIENTS AND METHODS: Case report. RESULTS: We describe a case of severe cyanide poisoning arising from CAM use. A severely agitated, encephalopathic, unresponsive 4-year-old boy (initial Glasgow Coma Scale of 3) with a history of metastatic ependymoma was brought to our emergency department by ambulance services. Initial blood gas analysis demonstrated severe metabolic/lactic acidosis. On detailed questioning of the parents, the use of CAM including intravenous and oral "vitamin B 17" (amygdalin) and oral apricot kernel was reported. After administering sodium thiosulfate, rapid improvement in his medical condition with complete recovery without need for further intensive care treatment was seen. Serum cyanide level was markedly elevated. CONCLUSIONS: Cyanide poisoning can be the cause of severe encephalopathy in children receiving CAM treatment with substances containing cyanogenic glycosides.

Congenital CLN disease in two siblings.

BACKGROUND: Neuronal ceroid lipofuscinoses (NCL) is characterized by a combination of retinopathy, dementia, and epilepsy. As a group, they encompass ten distinct biological and clinical entities and are the most common type of childhood neurodegenerative disease. PATIENTS AND METHODS: Case reports. RESULTS: We demonstrate the clinical course of two neonates (brother and sister) with infantile neuronal ceroid lipofuscinoses (NCL) (CLN 10 disease) presenting with intractable seizures and respiratory insufficiency immediately after birth. Characteristic clinical, radiological and pathological findings of this form of NCL are presented. CONCLUSIONS: We conclude that the diagnosis of CLN10 should be kept in mind as a differential diagnosis in newborns presenting with respiratory insufficiency and severe epilepsy that is largely refractory to anti-epileptic drugs (AED) treatment. Because of the severity of CLN10 disease and futility of treatment, important ethical issues arise when caring for children with this clinical entity.