Objective To study the clinical effect of early or late administration of caffeine citrate in the prevention and treatment of apnea in very low birth weight (VLBW) infants.Methods A total of 82 VLBW infants who were hospitalized and treated in the neonatal intensive care unit between June 2015 and May 2017 were enrolled. According to the age in days when caffeine citrate treatment was started, they were divided into early treatment group (< 3 days) with 22 infants and late treatment group (3- < 10 days) with 60 infants. A retrospective analysis was performed for their clinical data. The two groups were compared in terms of general information during the perinatal period, treatment process, and clinical outcome.Results Compared with the late treatment group, the early treatment group had a significantly lower birth weight (P=0.004), significantly shorter durations of mechanical ventilation and oxygen inhalation (P < 0.05), and a significantly lower incidence rate of bronchopulmonary dysplasia (P=0.032). There were no significant differences in other general information, treatment process, and clinical outcome between the two groups (P > 0.05).Conclusions Early administration of caffeine citrate can improve the prognosis of VLBW infants.

Objective To investigate the long-term prognosis of neonates with necrotizing enterocolitis (NEC).Methods A total of 83 preterm infants with NEC who survived and were discharged between December 2014 and September 2016 were enrolled and divided into surgery group (n=57) and non-surgery group (n=26). There were 0, 33 and 24 cases of stage I, Ⅱ and Ⅲ NEC respectively in the surgery group and 7, 19 and 0 cases respectively in the non-surgery group. The physical development and neurodevelopmental outcomes of the infants were followed up after discharge.Results Of the 83 infants, the mean corrected age at the end of follow-up was 21±6 months. Of the 83 infants, 31 (37%) had subnormal body weight, and the surgery group had a higher rate of subnormal body weight than the non-surgery group (P < 0.05). Twenty-two infants (27%) had subnormal body length and 14 children (17%) had subnormal head circumference among the 83 infants. Eighteen infants (22%) had motor developmental delay/developmental disorders, and the surgery group had a higher incidence rate of the disorders than the non-surgery group (28% vs 8%; P < 0.05). Five infants (6%) were diagnosed with cerebral palsy, among whom 4 were in the surgery group and 1 was in the non-surgery group.Conclusions Long-term physical development and neurodevelopmental outcomes may be adversely affected in neonates with NEC, in particular in those with severe conditions who need surgical treatment, suggesting that long-term follow-up should be performed for neonates with NEC.

Objective To investigate the screening indices and their cut-off values for full-term neonates carrying β-thalassemia gene.Methods A retrospective analysis was performed for the clinical data of 1 193 full-term neonates who underwent β-thalassemia screening (hemoglobin analysis with dried blood spots on neonatal heel blood filter paper and mutation detection of 17 β-globin genes). A multivariate logistic regression analysis was used to investigate the association between screening indices and β-thalassemia gene, and the receiver operating characteristic (ROC) curve was used to analyze the value of screening indices in determining the presence or absence of β-thalassemia gene.Results Of the 1 193 neonates, 638 carried β-thalassemia gene. Of the 1 193 neonates, 637 (53.39%) had no HbA₂, among whom 310 carried β-thalassemia gene and 327 did not carry this gene; 556 (46.61%) had HbA₂, among whom 328 carried β-thalassemia gene and 228 did not carry this gene. As for the neonates without HbA₂, the β-thalassemia gene group had a significantly lower HbA level and a significantly higher HbF level than the β-thalassemia gene-negative group (P < 0.01). As for the neonates with HbA₂, the β-thalassemia gene group had a significantly lower HbA level and significantly higher HbF and HbA₂/HbA ratio than the β-thalassemia gene-negative group (P < 0.01). In the neonates without HbA₂, HbA, gestational age, and HbA combined with gestational age had an area under the ROC curve (AUC) of 0.865, 0.515, and 0.870, respectively, in determining the presence or absence of β-thalassemia gene (P < 0.01), and HbA and HbA combined with gestational age had a similar AUC and a certain diagnostic value. In the neonates with HbA₂, HbA, HbA₂/HbA ratio, and HbA combined with HbA₂/HbA ratio had an AUC of 0.943, 0.885, and 0.978, respectively, in determining the presence or absence of β-thalassemia gene. The HbA combined with HbA₂/HbA ratio had the largest AUC. In the neonates without HbA₂, HbA had the largest AUC in determining the presence or absence of β-thalassemia gene at the cut-off value of 11.6%, with a sensitivity of 85.81% and a specificity of 79.82%. In the neonates with HbA₂, an HbA of 16.1%-22.0% and an HbA₂/HbA ratio of > 1.4 had the largest AUC in determining the presence or absence of β-thalassemia gene, with a sensitivity of 91.38% and a specificity of 91.89%.Conclusions HbA and HbA₂/HbA ratio are effective indices for screening out full-term neonates carrying β-thalassemia gene.

Objective To investigate the physical development of Uygur and Han neonates in Urumqi, China.Methods Live singleton neonates with a gestational age of 28-42 weeks who were born in the First Affiliated Hospital of Xinjiang Medical University and Maternal and Child Health Care Hospital from December 2014 to May 2017 were enrolled, and their body weight, body length, head circumference, and chest circumference at birth were measured. The cubic curve fitting method was used to plot the smooth curves of body weight, body length, head circumference, and chest circumference.Results A total of 5 027 singleton neonates with a gestational age of 28-42 weeks were enrolled, with 2 625 boys and 2 402 girls. The average values of birth weight, body length, head circumference, and chest circumference, Quetelet index, and Ververck index of Uygur/Han boys and girls with a gestational age of 28-42 weeks were obtained, and related smoothed percentile curves were plotted. There were some differences between Uygur and Han neonates in the average values of some growth and development indices. The Quetelet index and the Ververck index of Uygur and Han neonates increased with the increase in gestational age, and the Uygur neonates had a higher Ververck index than the Han neonates.Conclusions There are differences in the levels of some growth and development indices and Ververck index between the Uygur and Han neonates in Urumqi. The average values of body weight, body length, chest circumference, and head circumference at birth, Quetelet index, and Ververck index of Uygur and Han neonates with a gestational age of 28-42 weeks and their smoothed percentile curves can provide a reference for the assessment of neonatal growth and development in Urumqi.

Objective To reveal the current research status on stem cell transplantation in the treatment of neonates with hypoxic-ischemic encephalopathy (HIE), and to summarize the recent hotspots of the research in this field.Methods Using the key words of "stem cells" and "HIE", a computerized search was performed for the articles in English published before June 1, 2018 in PubMed, EMBASE, and Web of Science. Microsoft Office Excel 2013 was used for the statistical analysis of key words. Bicomb 2.0 and VOSviewer 1.6.6 were used for the cluster analysis of hot words and plotting of knowledge maps, respectively.Results A total of 106 articles were included and 43 high-frequency key words were extracted. The words of "cell transplantation" and "hypoxia-ischemia" were in the core position of the co-word map. The cluster analysis showed that the studies of stem cell transplantation in the treatment of neonatal HIE mainly focused on umbilical cord blood cell transplantation (32.6%), mesenchymal stem cells and neural stem cells (29.5%), perinatal brain injury (28.1%), and other topics (9.8%).Conclusions In the current studies of stem cell transplantation in the treatment of neonatal HIE, umbilical cord blood cell transplantation, mesenchymal stem cells, neural stem cells, and perinatal brain injury are popular research topics at different levels.

Objective To investigate the etiology and clinical features of epilepsia partialis continua (EPC) in children.Methods A retrospective analysis was performed for the clinical features, diagnosis and treatment of six children with EPC, and the clinical and laboratory features and prognosis were compared between the children with different etiologies.Results There were five girls and one boy, with an onset age ranging from one year and seven months to nine years. Two were diagnosed with Rasmussen encephalitis, one was diagnosed with focal cortical dysplasia, one was diagnosed with Alpers syndrome caused by POLG gene mutation, one was diagnosed with Angelman syndrome, and one was diagnosed with tuberculous meningitis. The latter two children had the predisposing factors for acute encephalopathy induced by status epilepticus and craniocerebral operation during the onset of EPC, while the other four children had natural progression of EPC. All the children had focal seizures except EPC, and symptoms included automatism, bilateral asymmetric tonic seizure, deflection, complex motor, and autonomic symptoms, with disturbance of consciousness in some children. EPC often lasted for several days or even several months. All children had abnormalities on head MRI, including local abnormal signal, cortex swelling, diffusive brain atrophy or brain atrophy at one side, local cortex thickening, and cortical necrosis. Head PET/CT scan was performed for three children and found local hypermetabolism or co-existence of hypermetabolism and hypometabolism. All the children had abnormalities on electroencephalography (EEG), with cerebral, hemispheric, or diffusive distribution of abnormal electrical activities, and during the onset of EPC, some EEG changes were recognizable and some were difficult to identify. All the children with EPC were not sensitive to antiepileptic drugs. EPC was relatively self-limiting in the child with Angelman syndrome. The child with focal cortical dysplasia underwent resection of epileptic foci and had good postoperative control, without neurological dysfunction. The child with Rasmussen encephalitis underwent functional hemispherectomy and had no attack after surgery, with neurological dysfunction. The child with Alpers syndrome had the worst prognosis.Conclusions EPC is a special type of epileptic seizures. Immune inflammation and metabolic etiologies are the main causes of EPC in children, and the selection of treatment regimens, treatment outcome, and prognosis depend on etiology.

This article reports a case of limb-girdle muscular dystrophy type 1B (LGMD1B) caused by a novel splicing heterozygous mutation in the LMNA gene. The proband presented with progressive aggravation of weakness in walking. There was no atrophy of the scapular muscles and the lower-extremity proximal muscles, with normal muscle tension of the extremities, grade 4 muscle strength in the upper and lower extremities, and positive Gower sign. The level of creatine kinase was 779 U/L. Muscle hematoxylin-eosin staining showed muscular dystrophy, and there was no significant reduction in the expression of Lamin A protein. Second-generation sequencing revealed a novel splicing heterozygous mutation, c.810+2T > C, in the LMNA gene, while this locus was normal in his parents. GERP++RS software predicted that the mutation site was highly conservative. Human Splice Finder and Spliceman software predicted that the mutation might be a pathogenic mutation. ExPASy software predicted that the new amino acid sequence became shorter. There were two sequences of mRNA in the patient's muscle:one was the normal sequence, which accounted for 92.2%; the other was partial intron 4 retention, which was the abnormal splice variant accounting for 7.8%. LGMD1B is a type of autosomal dominant inherited myopathy caused by a mutation in the LMNA gene located on the autosomal 1q22. This study extends the mutation spectrum of the LMNA gene and provides help to the diagnosis of LGMD1B.

Objective To study the protective effect of vitamin A on residual pancreatic β cell function in children with type 1 diabetes mellitus (T1DM) and its mechanism.Methods A total of 46 children with T1DM (with a course of disease of 0.5-1 year) were randomly divided into an intervention group and a non-intervention group (n=23 each). The children in both groups were given insulin treatment, and those in the intervention group were also given vitamin A at a daily dose of 1 500-2 000 IU. A total of 25 healthy children were enrolled as the control group. The daily dose of insulin was calculated for the children with T1DM, and the serum levels of glycosylated hemoglobin (HbA1C), stimulated C-peptide, vitamin A, and interleukin-17 (IL-17) were measured before intervention and 3 months after intervention.Results Before vitamin A intervention, the intervention group and the non-intervention group had a significantly lower serum level of vitamin A and a significantly higher level of IL-17 than the control group (P < 0.01). After 3 months of intervention, the intervention group had significantly lower serum IL-17 level and insulin dose and a significantly higher level of stimulated C-peptide than the non-intervention group (P < 0.05).Conclusions Vitamin A may protect residual pancreatic β cell function, possibly by improving the abnormal secretion of IL-17 in children with T1DM.

Objective To investigate the influence of demographic and clinical characteristics, stress, and coping style on disease self-management in children and adolescents with type 1 diabetes.Methods A cross-sectional survey was performed to select 149 children and adolescents with type 1 diabetes (aged 8-20 years). Related data were collected using the questionnaires and scales on general information, diabetes self-management, perceived stress, and coping style.Results Of the 149 children and adolescents, 37(24.8%) had high stress. Compared with the school-aged children, the adolescents had higher stress level and were more likely to present with negative coping style (P < 0.05). The multiple linear regression analysis showed that the children whose mothers had an educational level at or above senior high school, who had a low stress level, and who adopted positive coping measures had a higher level of diabetes self-management (P < 0.05).Conclusions Nearly a quarter of the children and adolescents with type 1 diabetes have a high stress level. When delivering the education on diabetes self-management to children and adolescents, healthcare workers should focus on the families whose mothers have an educational level at or below junior high school. Strategies should aim at reducing stress by encouraging positive coping styles.

A retrospective analysis was performed for the clinical data of four children with Epstein-Barr virus (EBV)-related acute liver failure. There were two boys and two girls with a median age of 10 months (range 8.5-44 months). Of the four children, three were diagnosed with infectious mononucleosis (IM), among whom two met the diagnostic criteria of hemophagocytic lymphohistiocytosis (HLH), and one was diagnosed with past EBV infection. All the children had positive EBV DNA in blood and all had pyrexia, hepatomegaly, and jaundice on admission. Three children had the symptom of splenomegaly, ascites, or vomiting. Two children had enlargement of cervical lymph nodes, skin rash, or pleural effusion. One child had gastrointestinal bleeding or stage 2 hepatic encephalopathy. All the children had an abnormal lymphocyte count of < 10%, and only one child had leukocytosis and thrombocytopenia. Among the four children, alanine aminotransferase level increased by 10-100 times; total bilirubin level increased by 3-5 times; lactate dehydrogenase level increased by many 10 times; prothrombin time prolonged significantly. All the children were given antiviral therapy with intravenously injected acyclovir or ganciclovir, as well as hepatocyte growth factor to promote hepatocyte growth and hormone to alleviate inflammatory response. Two children were given plasma exchange in addition, among whom one was given the combination of continuous venovenous hemodiafiltration. Two children with HLH were given chemotherapy according to the HLH-2004 regimen. Three children survived, and one child with HLH died of multiple organ failure. It is concluded that EBV infection can cause acute liver failure and that early use of multimodality therapy including blood purification may be beneficial for prognosis in these children.

Objective To study the clinical features and risk factors of pertussis in children.Methods A retrospective analysis was performed for the clinical data and laboratory markers for immune function of 253 hospitalized children with pertussis. A total of 314 hospitalized children with cough were used as the control group. Quantitative real-time PCR was used to detect Bordetella pertussis DNA. The clinical data of both groups were collected to analyze the risk factors for pertussis.Results A total of 23 typical clinical parameters were compared between the pertussis and control groups, and there were significant differences in only 10 clinical parameters between the two groups (P < 0.01). As for the complications observed in the two groups, the pertussis group had a significantly lower incidence rate of myocarditis than the control group (P < 0.05). The pertussis group had significantly lower levels of serum globulin and IgM than the control group (P < 0.05). Compared with the control group, the pertussis group had a significantly higher proportion of children with a lack of diphtheria-pertussis-tetanus immunization or timely immunization and a contact history of suspected pertussis patients (P < 0.05). A lack of vaccine immunization or timely immunization and a contact history of suspected pertussis patients were risk factors for pertussis (P < 0.05).Conclusions The clinical features are not typical in children with pertussis. Quantitative real-time PCR for detecting Bordetella pertussis DNA helps with the early diagnosis of atypical pertussis. Infants/toddlers should be immunized in time and be isolated from suspected pertussis patients to reduce the incidence of pertussis.

Objective To study the cognitive neural mechanism of working memory impairment in children with primary nocturnal enuresis using event-related potential (ERP).Methods A total of 14 children with primary nocturnal enuresis were enrolled as enuresis group, and 14 normal children were enrolled as control group. The learning-recognition task test was applied, and the ERP components (P2, N2, and P3) at Fz lead while identifying old pictures (learned) and new ones (unlearned) were measured and compared between the two groups.Results While identifying the old pictures, the enuresis group had a lower amplitude of P2 and N2 than the control group (P < 0.05). There were no significant differences between the two groups in the latency of P2, N2, and P3 and the amplitude of P3. While identifying the new pictures, the enuresis group had a longer latency of P2 and a significantly lower amplitude of N2 than the control group (P < 0.05). There were no significant differences between the two groups in the amplitude of P2 and P3 and the latency of N2 and P3.Conclusions Compared with normal children, the children with primary nocturnal enuresis have reduced abilities of classified information extraction, a prolonged reaction time, and reductions in memory capacity, memory consolidation, and conflict monitoring, which causes working memory impairment.

Objective To investigate the association between parental feeding behaviors and body mass index (BMI) of children, and to provide a scientific basis for the prevention and intervention of overweight and obesity in children.Methods Stratified random cluster sampling was used to select 976 children from 7 kindergartens in Xinshi District of Urumqi, and a questionnaire survey and physical measurement were performed to obtain related data.Results A total of 976 questionnaires were distributed and 924 (94.7%) usable questionnaires were collected. The overall detection rates of underweight, overweight, and obesity in children were 3.1% (29 children), 9.2% (85 children), and 6.7% (62 children), respectively. The highest level of parental feeding behavior was monitoring, followed by restriction and pressure to eat. The parents of the Han children had significantly higher levels of restriction and pressure to eat than those of the Uygur children (P < 0.01). As for parental feeding behaviors, restriction to eat was positively correlated with BMI of the Han and Uygur boys (P < 0.01); pressure to eat was negatively correlated with BMI of the Han boys and girls (P < 0.01) and was positively correlated with BMI of the Uygur boys and girls (P < 0.01); monitoring was negatively correlated with BMI of the Han and Uygur boys and girls (P < 0.05). Among the parents of the Han and Uygur boys, the parents of the overweight/obese children had significantly higher scores of restriction to eat than those of the children with normal weight (P < 0.05); among the parents of the Uygur boys and girls, the parents of the overweight/obese children had significantly higher scores of pressure to eat than those of the children with normal weight (P < 0.01); among the parents of the Uygur and Han boys and girls, the parents of the overweight/obese children had significantly lower scores of monitoring than those of the children with normal weight (P < 0.01).Conclusions The parental feeding behavior is good in Urumqi, and the parental feeding behavior of the Uygur children is a little better than that of the Han children. Parental feeding behavior is closely correlated with BMI of children, and such correlation differs across ethnic groups and sexes. A high level of monitoring and low levels of restriction and pressure to eat may help to prevent and control the development of overweight and obesity in children.

A girl, aged 1 year and 9 months, was found to have hypertriglyceridemia in the neonatal period, with unusual facies and signs of dark skin all over the body, disappearance of subcutaneous adipose, acanthosis nigricans of the neck, excessive and thick hair, empty cheeks, muscle hypertrophy of the extremities, hepatomegaly, and neutrophil deficiency. Whole exome sequencing of monogenic disorder revealed a homozygote mutation in the BSCL2 gene, c.974 (exon 7)_c.975 (exon 7) insG. Her parents were heterozygotes for this locus. The girl was diagnosed with congenital generalized lipodystrophy (CGL), but the association between CGL and neutrophil deficiency remained unclear. Triglyceride was maintained at a normal level after the treatment with a low-fat and high-carbohydrate diet, and there were no obvious changes in signs. CGL is a rare autosomal recessive systemic disease manifested as disappearance of systemic subcutaneous adipose, muscle hypertrophy of the extremities, and metabolic disorders in the neonatal period, such as high triglycerides, hyperinsulinemia, and hyperglycemia. About 95% of CGL cases are caused by mutations in the AGPAT2 or BSCL2 gene.

Objective To study the expression and significance of tight junction proteins (claudin-2, claudin-10, and claudin-17) in a mouse model of renal ischemia-reperfusion injury.Methods A total of 152 male C57BL/6 mice were randomly assigned to control group (n=8), sham-operation group (n=72), and model group (n=72). The renal pedicles at both sides were clamped for 30 minutes to establish a mouse model of renal ischemia-reperfusion injury. According to the time points of reperfusion (0, 3, 6, 12, 24, 48, and 72 hours and 5 and 7 days), the sham-operation group and the model group were further divided into 9 subgroups, with 8 mice in each subgroup. RT-PCR and immunohistochemistry were used to measure the mRNA and protein expression of claudin-2, claudin-10, and claudin-17 in renal tissue.Results The control and sham-operation groups had no significant changes in the mRNA and protein expression of claudin-2, claudin-10, and claudin-17 in renal tissue over the time of reperfusion (P > 0.05). Compared with the control and sham-operation groups, the model group had decreased mRNA and protein expression of claudin-2 and claudin-10 after reperfusion, and the expression decreased gradually over the time of reperfusion, with the lowest levels at 24 hours of reperfusion (P < 0.05). Compared with the control and sham-operation groups, the model group had increased mRNA and protein expression of claudin-17 after reperfusion, and the expression increased gradually over the time of reperfusion, with the highest mRNA level at 12 hours and the highest protein level at 24 hours of reperfusion (P < 0.05).Conclusions Renal ischemia-reperfusion injury is closely associated with abnormal expression of tight junction proteins claudin-2, claudin-10, and claudin-17.

Objective To study the effect of montelukast sodium (MK), a leukotriene receptor antagonist, and bacterial lysates (OM-85BV), used alone or in combination, on airway remodeling and the expression of transforming growth factor-β1 (TGF-β1) and Smad7 in guinea pigs with bronchial asthma and their correlation.Methods A total of 40 male Hartley guinea pigs were randomly divided into normal control group, asthma group, MK group, OM-85BV group, and MK+OM-85BV group, with 8 guinea pigs in each group. Intraperitoneal injection of 10% ovalbumin (OVA) for sensitization and aerosol inhalation of 1% OVA for challenge were performed to establish a model of airway remodeling of asthma in all of the groups apart from the normal control group, which were treated with normal saline. In the stage of challenge by aerosol inhalation, the guinea pigs in the MK, OM-85BV, and MK+OM-85BV groups were given corresponding suspension by gavage, and those in the normal control and asthma groups were given an equal volume of normal saline by gavage. Bronchoalveolar lavage fluid (BALF) of the guinea pigs was collected within 24 hours after challenge, and ELISA was used to measure the levels of TGF-β1 and Smad7 in BALF. The guinea pigs were sacrificed and the pathological section of lung tissue was prepared to observe the degree of airway remodeling. An image analysis technique was used to measure perimeter of the basement membrane (Pbm), total bronchial wall area (Wat), and airway bronchial smooth muscle area (Wam). Pearson linear regression was used to investigate the correlation between two variables.Results According to the lung pathological section, compared with the normal control group, the asthma, MK, OM-85BV, and MK+OM-85BV groups had significant thickening of bronchial smooth muscle and alveolar wall, significantly higher Wat/Pbm and Wam/Pbm, a significantly higher level of TGF-β1, and a significantly lower level of Smad7 (P < 0.05). Compared with the asthma group, the MK, OM-85BV, and MK+OM-85BV groups had a significant improvement in pathological injury, significantly lower Wat/Pbm and Wam/Pbm, a significantly lower level of TGF-β1, and a significantly higher level of Smad7 (P < 0.05). The MK+OM-85BV group had significantly greater improvements than the MK group and the OM-85BV group (P < 0.05). The expression of TGF-β1 was negatively correlated with that of Smad7 and positively correlated with Wat/Pbm and Wam/Pbm, and the expression of Smad7 was negatively correlated with Wat/Pbm and Wam/Pbm (P < 0.01).Conclusions MK and OM-85BV, used alone or in combination, can reduce airway remodeling in guinea pigs with asthma, and MK combined with OM-85BV has the best effect, possibly by reducing TGF-β1 expression, increasing Smad7 expression, and improving the TGF-β1/Smad7 imbalance.

Iron deficiency (ID) is the most common micronutrient deficiency in children. Due to insufficient iron storage at birth and rapid catch-up growth after birth, preterm infants tend to have a high incidence rate of ID. During the critical period of brain development, ID alters iron-dependent neurometabolism, neurochemistry, neuroanatomy, and gene/protein profiles. This affects the central nervous system and causes the change in neurocognitive and behavioral development. Iron supplementation in infancy cannot reverse neurodevelopmental impairment caused by perinatal ID. The influence of ID on neurodevelopment is time-and region-specific, and in the high-risk population, early diagnosis and optimal iron treatment may help with the recovery of brain function and improve quality of life and long-term prognosis in preterm infants.

Most critically ill children are in a state of serious stress and tend to develop malnutrition, which may reduce the body's ability to fight against diseases and repair damaged tissues and thus aggravate their conditions. Reasonable and effective nutritional support for critically ill children can improve their nutritional status and prognosis, and so it is necessary to offer nutritional support for critically ill children. This article reviews the research on nutritional support for critically ill children and the current status of clinical application. It also introduces the main methods for nutritional support, including enteral nutrition and parenteral nutrition, and elaborates on the new methods for nutritional support, such as early enteral nutrition, enteral immunonutrition, and supplementary parenteral nutrition, in order to provide a reference for nutritional support for critically ill children.