[Risk factors for metabolic bone disease of prematurity in very/extremely low birth weight infants: a multicenter investigation in China].

OBJECTIVE: To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP. RESULTS: The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation (P < 0.05). Compared with the non-MBDP group, the MBDP group had significantly higher incidence rates of neonatal sepsis, anemia, hypocalcemia, and retinopathy of prematurity (P < 0.05). The MBDP group had a significantly lower mean feeding speed, a significantly higher age when reaching total enteral feeding, and a significantly longer duration of parenteral nutrition (P < 0.05). The use rate of caffeine citrate in the MBDP group was significantly higher, but the use rate of erythropoietin was significantly lower than that in the non-MBDP group (P < 0.05). The multivariate logistic regression analysis showed that gestational age < 32 weeks, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis were risk factors for MBDP (P < 0.05). CONCLUSIONS: A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.

[Association of different stages of histological chorioamnionitis with respiratory distress syndrome in preterm infants with a gestational age of < 32 weeks].

OBJECTIVE: To study the association of different stages of histological chorioamnionitis (HCA) with the incidence rate and severity of respiratory distress syndrome (RDS) in preterm infants. METHODS: Related data were collected from the infants and their mothers who were treated in the Neonatal Intensive Care Unit of Qingdao Women and Children's Hospital, Qingdao University, from January 2018 to June 2020. According to the presence or absence of HCA and its stage, the infants were divided into four groups: control (n=109), early-stage HCA (n=126), middle-stage HCA (n=105), and late-stage HCA (n=36). The four groups were compared in terms of gestational age, birth weight, sex, maternal age, placental abruption, prenatal use of antibiotics, and incidence rate of RDS. The correlation between HCA stage and RDS severity was analyzed. RESULTS: Compared with the control and late-stage HCA groups, the early-stage HCA group had a significantly lower incidence rate of placental abruption and a significantly higher rate of prenatal use of antibiotics (P < 0.05), and the early-stage HCA group had a significantly lower incidence rate of RDS than the control group (P < 0.05). The multivariate logistic regression analysis showed that early-, middle-, and late-stage HCA were protective factors against RDS (P < 0.05). The Spearman test showed that the severity of RDS in preterm infants was not correlated with the HCA stage (P > 0.05). CONCLUSIONS: Early-, middle-, and late-stage HCA can reduce the incidence rate of RDS in preterm infants. HCA stage may not be correlated with RDS severity in preterm infants, which needs to be verified by further research.

[Association between S100B gene polymorphisms and hand, foot and mouth disease caused by enterovirus 71 infection].

OBJECTIVE: To investigate the association between rs9722 polymorphisms in the S100B gene and hand, foot and mouth disease (HFMD) caused by enterovirus 71. METHODS: A total of 124 HFMD children with enterovirus 71 infection were enrolled as subjects, and 56 healthy children were enrolled as control group. The rs9722 polymorphisms in the S100B gene were detected for both groups, and the serum level of S100B protein was measured for 74 HFMD children. RESULTS: The rs9722 locus of the S100B gene had three genotypes, CC, CT, and TT, and the genotype frequencies were in accordance with Hardy-Weinberg equilibrium. Compared with the control group, the HFMD group had significant increases in the frequencies of TT genotype and T allele (P<0.01). Children with severe HFMD caused by enterovirus 71 infection had significantly higher frequencies of TT genotype and T allele than those with moderate or mild HFMD (P<0.05). Compared with the cured patients, the patients with poor prognosis had significant increases in the frequencies of TT genotype and T allele in the rs9722 locus of the S100B gene (P<0.05). Among the 74 children with HFMD, the children with TT genotype had the highest serum level of S100B protein, and those with CC genotype had the lowest level (P<0.01). CONCLUSIONS: T allele in the rs9722 locus of the S100B gene might be a risk factor for severe HFMD caused by enterovirus 71 infection.

[Value of serum S100B protein and neuron-specific enolase levels in predicting the severity of hand, foot and mouth disease].

OBJECTIVE: To study the value of serum S100B protein and neuron-specific enolase (NSE) levels in predicting the severity of hand, foot and mouth disease (HFMD). METHODS: Ninety children with HFMD were classified into three groups: common type, severe type, and critical type (n=30 each). Thirty healthy children were randomly selected as the control group. ELISA was used to measure serum levels of S100B protein and NSE before and at 7 days after treatment. The receiver operating characteristic (ROC) curve was used to evaluate the prediction efficiency of S100B protein and NSE for the severity of HFMD. RESULTS: The critical type group had significant increases in the serum levels of S100B protein and NSE compared with the other three groups (P<0.01). The severe type group had significant increases in serum levels of S100B protein and NSE compared with the common type and control groups (P<0.01). The critical type and severe type groups had significant reductions in serum levels of S100B protein and NSE after treatment (P<0.05). Serum S100B protein had the highest Youden value of 0.611 at the cut-off value of 0.445 µg/L, with a sensitivity of 61% and a specificity of 100%, in the prediction of serious HFMD (including severe type and critical type HFMD). Serum NSE had the highest Youden value of 0.533 at the cut-off value of 5.905 µg/L, with a sensitivity of 80% and a specificity of 73%, in the prediction of serious HFMD. Combined measurements of these two parameters had a sensitivity of 86% and a specificity of 73% and had the highest predictive value for serious HFMD. CONCLUSIONS: The serum levels of S100B protein and NSE help to predict the severity and treatment outcomes of HFMD. Combined measurements of these two parameters has a higher predictive value for serious HFMD.

Analysis of In-hospital Neonatal Death in the Tertiary Neonatal Intensive Care Unit in China: A Multicenter Retrospective Study.

BACKGROUND: Globally, the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China. METHODS: All the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed. RESULTS: A total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents' concern about the long-term outcomes was the main reason of medical care withdrawal. CONCLUSIONS: Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.

Effect of Carvedilol on Serum Heart-type Fatty Acid-binding Protein, Brain Natriuretic Peptide, and Cardiac Function in Patients With Chronic Heart Failure.

OBJECTIVE: To observe the changes of serum heart-type fatty acid-binding protein (h-FABP) and brain natriuretic peptide (BNP) in children with chronic heart failure (CHF) and evaluate the effects of carvedilol. METHODS: A total of 36 patients with CHF, including 17 of endocardial fibroelastosis and 19 of dilated cardiomyopathy, were enrolled and were randomly divided into a carvedilol treatment group (group A) and a conventional treatment group (group B). Group A (n = 16) was treated with carvedilol and conventional treatment and group B (n = 20) was managed with conventional treatment only. Thirty healthy children were enrolled as controls. The concentrations of serum h-FABP and BNP were measured by enzyme-linked immunosorbent assay, and the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and cardiac index (CI) were measured by echocardiography. RESULTS: The concentrations of serum h-FABP and BNP in patients with CHF were significantly higher than in the control group (21.7 ± 4.3 ng/mL vs. 6.3 ± 1.7 ng/mL, 582.4 ± 180.6 pg/mL vs.31.2 ± 9.8 pg/mL, all P < 0.01), positively correlated with the degree of heart failure (all P < 0.01), and were both higher in groups endocardial fibroelastosis and dilated cardiomyopathy than in the control group (all P < 0.01), but there was no statistically significant difference between the 2 groups (P > 0.05). h-FABP concentration in patients with CHF was positively correlated with BNP (r = 0.78, P < 0.01) but negatively correlated with LVEF, LVFS, and CI (r = -0.65, -0.64, and -0.71, respectively; all P < 0.01). BNP concentration was also negatively correlated with LVEF, LVFS, and CI (r = -0.75, -0.61, and -0.79, respectively; all P<0.01). After treatment with carvedilol, the serum concentrations of h-FABP and BNP in group A were lower than in group B, and the magnitude of heart rate reduction, improvement of LVEF, LVFS, and CI, and reduction of left ventricular end-systolic diameter and left ventricular end-diastolic diameter in group A were all greater than in group B (all P < 0.01). Treatment with carvedilol had no adverse events. CONCLUSIONS: Serum concentrations of h-FABP and BNP can be used as biomarkers to evaluate the severity of heart failure, and carvedilol can significantly improve heart function in children with CHF.

Effects of inhaled nitric oxide in neonatal hypoxemic respiratory failure from a multicenter controlled trial.

BACKGROUND: Hypoxemic respiratory failure (HRF) is one of the most common causes for neonatal infants requiring aggressive respiratory support. Inhaled nitric oxide (iNO) has been established routinely as an adjunct to conventional respiratory support in developed countries. The aim of this study was to investigate effects of iNO in neonates with HRF in resource limited condition with no or limited use of surfactant, high frequency oscillatory ventilation (HFOV) and extracorporeal membrane oxygenation. METHODS: A non-randomized, open, controlled study of efficacy of iNO was conducted over 18 months. Eligible term and near-term neonates from 28 hospitals with HRF (oxygenation index > 15) were enrolled prospectively into two groups as either iNO or control. Oxygenation improvement and mortality as primary endpoint were determined in relation with dosing and timing of iNO, severity of underlying diseases, complications and burden. Intention-to-treat principle was adopted for outcome assessment. Response to iNO at 10 or 20 parts per million (ppm) was determined by oxygenation in reference to the control (between-group) and the baseline (within-group). RESULTS: Compared to 93 controls, initial dose of iNO at 10 ppm in 107 treated infants significantly improved oxygenation from first hour (P = 0.046), with more partial- and non-responders improved oxygenation with subsequent 20 ppm NO (P = 0.018). This effect persisted on days 1 and 3, and resulted in relatively lower mortalities (11.2% vs. 15%) whereas fewer were treated with surfactant (10% vs. 27%), HFOV (< 5%) or postnatal corticosteroids (< 10%) in both groups. The overall outcomes at 28 days of postnatal life in the iNO-treated was not related to perinatal asphyxia, underlying diseases, severity of hypoxemia, or complications, but to the early use of iNO. The cost of hospital stay was not significantly different in both groups. CONCLUSIONS: With relatively limited use of surfactant and/or HFOV in neonatal HRF, significantly more responders were found in the iNO-treated patients as reflected by improved oxygenation in the first three days over the baseline level. It warrants a randomized, controlled trial for assessment of appropriate timing and long-term outcome of iNO.

[Comorbidities in patients with cerebral palsy and their relationship with neurologic subtypes and Gross Motor Function Classification System levels].

OBJECTIVE: To analyze the comorbidities in patients with cerebral palsy (CP) from two perspectives as neurologic subtype and gross motor functions, and find their correlations. METHODS: Children with cerebral palsy treated in the rehabilitation center from January 2007 to June 2009 received the following examinations: intelligence capacity test, ophthalmologic consultation, language-speech test, brainstem auditory evoked potential and electroencephalogram. They were stratified according to both neurologic subtype and gross motor functions to detect the occurrence of comorbidities. RESULTS: Of all the 354 cases, 166 (46.89%) had mental retardation, 15 (4.24%) auditory limitations, 138 (38.98%) visual disorder, 216 (61.02%) language-speech disorder and 82 (23.16%) epilepsy. The frequency of individual comorbidities were distributed disproportionately between the different neurologic subtypes. Correlation analysis showed that there was a significant correlation between the spastic diplegia and the visual disorder (correlation coefficient = 0.26), between spastic hemiplegia and epilepsy (correlation coefficient = 0.17), between spastic quadriplegia and epilepsy and mental retardation (the correlation coefficient was 0.38 and 0.11, respectively) and between both dyskinetic and mixed children and language-speech disorder (the correlation coefficient was 0.24 and 0.27, respectively). The frequency of individual comorbidities was distributed disproportionately between the different neurologic subtypes and between the different GMFCS levels (P < 0.05), except for the frequency of visual disorders (chi(2) = 1.90, P > 0.05); and with the increase of the GMFCS levels, the burden of the comorbidities were more heavy and the incidence of the comorbidities was higher. Multi-comorbidities were relatively infrequently encountered in those with spastic hemiplegic or spastic diplegic children or patients whose GMFCS levels were I-III, while these entities occurred at a frequent level for those with spastic quadriplegic, dyskinetic, or mixed or children whose GMFCS levels were IV and V, and the differences were significant (P < 0.05). The mean GMFCS levels of children with spastic quadriplegic, dyskinetic or mixed CP were higher than level III, most of them had no ability of ambulation;while the mean GMFCS levels of spastic hemiplegic or spastic diplegic children were below level III, most of them could walk independently. CONCLUSIONS: There are correlations between the occurrence of the comorbidities such as mental retardation, auditory or visual impairments, language-speech disorders, epilepsy and the cerebral palsy subtype and the gross motor function levels. Clinicians should have a full recognition of these comorbidities, and we should have a cooperation between the different subjects to have an overall evaluation and rehabilitation and to improve the prognosis.

Selective head cooling with mild systemic hypothermia after neonatal hypoxic-ischemic encephalopathy: a multicenter randomized controlled trial in China.

OBJECTIVE: To investigate the efficacy and safety of selective head cooling with mild systemic hypothermia in hypoxic-ischemic encephalopathy (HIE) in newborn infants. STUDY DESIGN: Infants with HIE were randomly assigned to the selective head cooling or control group. Selective head cooling was initiated within 6 hours after birth to a nasopharyngeal temperature of 34 degrees+/-0.2 degrees C and rectal temperature of 34.5 degrees to 35.0 degrees C for 72 hours. Rectal temperature was maintained at 36.0 degrees to 37.5 degrees C in the control group. Neurodevelopmental outcome was assessed at 18 months of age. The primary outcome was a combined end point of death and severe disability. RESULTS: One hundred ninety-four infants were available for analysis (100 and 94 infants in the selective head cooling and control group, respectively). For the selective head cooling and control groups, respectively, the combined outcome of death and severe disability was 31% and 49% (OR: 0.47; 95% CI: 0.26-0.84; P=.01), the mortality rate was 20% and 29% (OR:0.62; 95% CI: 0.32-1.20; P=.16), and the severe disability rate was 14% (11/80) and 28% (19/67) (OR: 0.40; 95% CI: 0.17-0.92; P=.01). CONCLUSIONS: Selective head cooling combined with mild systemic hypothermia for 72 hours may significantly decrease the combined outcome of severe disability and death, as well as severe disability.

[Influence of congenital asymptomatic cytomegalovirus infection on development of infants].

OBJECTIVE: Human cytomegalovirus (HCMV) is a ubiquitous human-specific DNA virus and is the main cause of congenital virus infection worldwide. Although 90% of the congenitally infected infants are clinically asymptomatic at birth, evidences show that these infants are at risk for audiologic, neurologic, and developmental sequelae. The aim of this study was to evaluate the outcome of children with asymptomatic congenital human cytomegalovirus infection identified from a cohort of newborn infants screened for congenital HCMV infection compared with matched uninfected control subjects. METHODS: Between July 2003 and July 2005, eligible hospitalized infants were recruited into the cohort. Serum was collected within two weeks of birth and transported to the laboratory within 24 hours, and stored at -20 degrees C. Then Real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) for the presence of HCMV DNA was used as a screening tool for the detection of congenital cytomegalovirus infection. Asymptomatic congenital HCMV infection (ACCMV) was defined as detection of HCMV during the first 2 weeks of life in the absence of any abnormal signs, symptoms, or laboratory findings. The study enrolled 41 siblings with asymptomatic congenital HCMV infection and 21 children whose neonatal screening for congenital HCMV infection showed negative results. Then they were followed up prospectively for the first years of life. A pediatric assessment, including neonatal behavioral neurological assessment (NBNA) was performed at neonatal period by a qualified pediatrician, at which time the CMV status of the infants was not yet known. At one year of age other standardised clinical evaluations were performed by the pediatrician. The Bayley scale of infant development were used to determine the intellectual and neurological development deficits, and the age-adequate neurological examinations based on the criteria by Amiel-Tison to evaluate the general movements for neurological development. Hearing screening were completed for all children to determine their hearing status. Auditory brain-stem response (ABR) and distortion product otoacoustic emission (DPOAE) have been used to accurately diagnose moderate to profound congenital sensorineural hearing loss. RESULT: There was no significant difference between the mean NBNA score of HCMV group (38.8 +/- 2.75) and the control group (38.5 +/- 2.29) (t = 0.98, P > 0.05). Significant difference was found between the occurrence of hearing loss in infants born with asymptomatic congenital HCMV infection compared with the control group. Audiologic abnormalities (sensorineural hearing loss, SNHL) were present in 5 of 23 congenitally infected children, however, no hearing abnormalities were detected in uninfected children (chi2 = 6.94, P < 0.01). The mean Bayley score of HCMV group (MDI 106.86 +/- 10.24 and PDI 108.45 +/- 18.25) and the control group (MDI 107.49 +/- 19.31 and PDI 107.19 +/- 10.98) did not differ significantly (t = 0.33, P > 0.05, t = 0.35, P > 0.05). Otherwise, there was no significant difference in 52 Amiel-Tison neurological scale between the two groups. CONCLUSION: These data suggest that asymptomatic congenital cytomegalovirus infection may be associated with a broad range of audiologic differences in early infancy. Continued monitoring of their hearing status in the first years of life is necessary in these children because further progression of hearing loss is possible. However, asymptomatic congenital HCMV infection is not associated with abnormalities in growth, or neurodevelopmental deficits.