Objective To study the treatment and prognosis of pulmonary hemorrhage in preterm infants. Methods A total of 106 preterm infants diagnosed with pulmonary hemorrhage, who were hospitalized in the neonatal ward of Peking University Third Hospital between 2007 and 2016, were enrolled. These patients were divided into 2007-2011 group (34 cases) and 2012-2016 group (72 cases) according to the time of hospitalization, divided into conventional-frequency ventilation group (43 cases) and high-frequency oscillatory ventilation (HFOV) group (63 cases) according to the respiratory support method used after the development of pulmonary hemorrhage, and divided into non-operation group (34 cases) and operation group (14 cases) according to whether PDA ligation was performed for the unclosed PDA before pulmonary hemorrhage. The general data, treatment, and prognosis were compared between different groups. Results Compared with the 2007-2011 group, the 2012-2016 group had higher rates of HFOV and PDA ligation (P < 0.05), a lower mortality rate during hospitalization (P < 0.05), a longer length of hospital stay (P < 0.05), and higher incidence rates of intracranial hemorrhage and bronchopulmonary dysplasia (P < 0.05). Compared with the conventional-frequency ventilation group, the HFOV group had a lower mortality rate during hospitalization (P < 0.05), a longer length of hospital stay (P < 0.05), and higher incidence rates of intracranial hemorrhage and bronchopulmonary dysplasia (P < 0.05). Compared with the non-operation group, the operation group had a lower mortality rate during hospitalization (P < 0.05), a longer length of hospital stay (P < 0.05), and higher incidence rates of intracranial hemorrhage and bronchopulmonary dysplasia (P < 0.05). Conclusions The application of HFOV and PDA ligation can improve the survival rate of preterm infants with pulmonary hemorrhage, but the incidence of intracranial hemorrhage and bronchopulmonary dysplasia is also increased.

Objective To study the clinical features and prognosis of preterm infants with varying degrees of bronchopulmonary dysplasia (BPD). Methods The clinical data of 144 preterm infants with a gestational age of < 32 weeks who were admitted to the neonatal intensive care unit from March 2014 to March 2016 and were diagnosed with BPD were collected. According to the severity of BPD, these preterm infants were divided into mild group with 81 infants and moderate/severe group with 63 infants. The two groups were compared in terms of perinatal risk factors, treatment, comorbidities, complications, and prognosis of the respiratory system. Results Compared with the mild BPD group, the moderate/severe BPD group had a significantly higher gestational age and rate of small-for-gestational-age (SGA) infants (P < 0.05), as well as a significantly higher rate of severe preeclampsia and a significantly lower rate of threatened preterm labor (P < 0.05). Compared with the mild BPD group, the moderate/severe BPD group had a significantly higher percentage of infants who needed mechanical ventilation at 2 weeks after birth, longer duration of mechanical ventilation, total time of oxygen therapy, and length of hospital stay, and higher incidence rates of pneumonia and cholestasis (P < 0.05), as well as a significantly lower application rate of caffeine citrate (P < 0.05). The multivariate logistic regression analysis showed that SGA birth (OR=5.974, P < 0.05), pneumonia (OR=2.590, P < 0.05), and mechanical ventilation required at 2 weeks after birth (OR=4.632, P < 0.05) were risk factors for increased severity of BPD. The pulmonary function test performed at the corrected gestational age of 40 weeks showed that compared with the mild BPD group, the moderate/severe BPD group had significantly lower ratio of time to peak tidal expiratory flow to total expiratory time, ratio of volume to peak tidal expiratory flow to total expiratory volume, and tidal expiratory flow at 25% remaining expiration (P < 0.05). The infants were followed up to the corrected gestational age of 1 year, and the moderate/severe BPD group had significantly higher incidence rates of recurrent hospital admission for pneumonia and recurrent wheezing (P < 0.05). Conclusions SGA birth, pneumonia, and prolonged mechanical ventilation are associated with increased severity of BPD. Infants with moderate or severe BPD have poor pulmonary function and may experience recurrent infection and wheezing.

Objective To establish the intrauterine growth curve of twin neonates, and to investigate the intrauterine growth status of twin neonates. Methods Cross-sectional cluster sampling was performed for an on-the-spot investigation of 1 296 live twin neonates who were born in two hospitals in Shenzhen between April 2013 and September 2015. The Lambda-Mu-Sigma method was used for the curve fitting of body weight, body length, head circumference, chest circumference, and crown-rump length. Results The means and 3rd-97th percentile intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length were obtained for the 1 296 twin neonates with a gestational age of 27-40 weeks. The curve values of the 1 296 twin neonates for body weight, body length, head circumference, chest circumference, and crown-rump length were all lower than those of singleton neonates in Shenzhen that had been reported, and the difference increased with increasing gestational age. Conclusions The intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length of twin neonates with a gestational age of 27-40 weeks in Shenzhen obtained in this study can provide a reference for evaluating the intrauterine growth status of twin neonates among the current population in Shenzhen.

Objective To study the influence of acute pancreatitis in pregnancy (APIP) on pregnancy outcomes and neonates. Methods A retrospective analysis was performed for 33 APIP patients and 31 neonates born alive. Results Of the 33 APIP patients, 26 (79%) developed APIP in the late pregnancy. Fourteen (45%) patients had hyperlipidemic APIP, 13 (42%) had biliary APIP, and 4 (13%) had other types of APIP. According to the severity, 22 (67%) were mild APIP, 5 (15%) were moderate APIP, and 6 were severe APIP. None of the 33 APIP patients died. Among the 20 patients with term delivery, 11 underwent termination of pregnancy; among the 10 patients with preterm delivery, 9 underwent termination of pregnancy; two patients experienced intrauterine fetal death, and one experienced abortion during the second trimester. Among the 31 neonates born alive (two of them were twins), 1 (3%) died, 12 (39%) experienced neonatal hyperbilirubinemia, 8 (26%) had neonatal hypoglycemia, 6 (19%) had neonatal respiratory distress syndrome, 5 (16%) experienced infectious diseases, and 2 (6%) experienced intracranial hemorrhage. The hyperlipidemic APIP group had a higher percentage of patients undergoing termination of pregnancy than the biliary APIP and other types of APIP groups (P < 0.05). The incidence rate of preterm infants in the moderate APIP was higher than in the mild and severe APIP groups (P < 0.05). The mean birth weights of neonates were the lowest in the moderate APIP group. The incidence rates of neonatal respiratory distress syndrome, intracranial hemorrhage, and infectious disease were the lowest in the mild APIP group (P < 0.05). Conclusions APIP can lead to adverse pregnancy outcomes and neonatal diseases, which are associated with the severity of pancreatitis.

Sodium taurocholate cotransporting polypeptide (NTCP) deficiency is an inborn error of bile acid metabolism caused by mutations of SLC10A1 gene. This paper reports the clinical and genetic features of a patient with this disease. A 3.3-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 3 months. Physical examination revealed moderate jaundice of the skin and sclera. The liver was palpable 3.5 cm below the right subcostal margin with a medium texture. Serum biochemistry analysis revealed markedly elevated bilirubin (predominantly direct bilirubin) and total bile acids (TBA), as well as decreased 25-OH-VitD level. On pathological analysis of the biopsied liver tissue, hepatocyte ballooning and cholestatic multinucleate giant cells were noted. The lobular architecture was distorted. Infiltration of inflammatory cells, predominantly lymphocytes, was seen in the portal tracts. In response to the anti-inflammatory and liver protective drugs as well as fat-soluble vitamins over 2 months, the bilirubin and transaminases levels were improved markedly while the TBA kept elevated. Because of persisting hypercholanemia on the follow-up, SLC10A1 gene analysis was performed at his age of 17.2 months. The child proved to be a homozygote of the reportedly pathogenic variant c.800C > T (p. Ser267Phe), while the parents were both carriers. NTCP deficiency was thus diagnosed. The infant was followed up until 34.3 months old. He developed well in terms of the anthropometric indices and neurobehavioral milestones. The jaundice disappeared completely. The liver size, texture and function indices all recovered. However, the hypercholanemia persisted, and the long-term outcome needs to be observed.

This research investigated the clinical features of immunodeficiency disease and the features of the mutation of its pathogenic genes. All 7 patients were boys aged 5 months to 4 years and 6 months and had a history of recurrent respiratory infection and pneumonia, low levels of IgM and IgG, and abnormal absolute values or percentages of lymphocyte subsets. High-throughput sequencing showed c.1684C > T mutations in the BTK gene in patient 1 and IVS8+2T > C splice site mutations in the BTK gene in patient 2. Both of these mutations came from their mothers. Patients 3, 4, and 5 had mutations in the IL2RG gene, i.e., c.298C > T, IVS3-2A > G, and c.164T > A, among which c.164T > A mutations had not been reported. Patient 6 had c.204C > G mutations in the RAG2 gene. Patient 7 had complex heterozygous mutations of c.913C > T and c.824G > A in the RAG2 gene, which came from his father and mother, respectively. Patients with immunodeficiency disease have abnormal immunological indices, and high-throughput sequencing helps to make a definite diagnosis.

Objective To investigate the clinical significance of BRAF-V600E mutation in children with Langerhans cell histiocytosis (LCH). Methods Real-time fluorescence quantitative PCR was used to detect BRAF-V600E mutation in paraffin-embedded tissue samples from 26 children with LCH. A retrospective analysis was performed for the association of BRAF-V600E mutation with clinical features and prognosis of children with LCH. Results Of the 26 children, 25 received standard chemotherapy, with a 2-year overall survival (OS) rate of 100% and a 2-year event-free survival (EFS) rate of 88%. Of the 26 pathological samples, 18 (70%) came from bone tissue, and the positive rate of BRAF-V600E mutation reached 50% (13/26). The positive rate of BRAF-V600E gene mutation was not associated with age, sex, affected organ, clinical classification, early treatment response, recurrence, and 2-year OS and EFS rates of the children with LCH (P > 0.05), but it was associated with clinical grouping of LCH (P < 0.05). Conclusions Children with LCH tend to have a high OS rate and a high incidence rate of BRAF-V600E mutation. BRAF-V600E mutation is associated with clinical grouping of LCH.

Objective To investigate the clinical features and prognosis of malignancy-associated hemophagocytic lymphohistiocytosis (MAHS) in children. Methods A retrospective analysis was performed for the primary diseases, clinical features, and prognosis of 24 children with MAHS. Results Among the 24 children, 11 (46%) had MAHS induced by tumor and 13 (54%) had chemotherapy-associated MAHS. As for primary diseases, 17 children had acute leukemia, 6 had lymphoma, and 1 had neuroblastoma. The most common clinical manifestations were pyrexia, respiratory symptoms, and hepatosplenomegaly. The most common laboratory abnormalities were hemocytopenia, elevated serum ferritin, and elevated lactate dehydrogenase. Of the 24 children, 22 were treated according to the HLH-2004 protocol and 2 gave up treatment; 18 children died, 1 was lost to follow-up, and 5 survived. The survival time ranged from 3 days to 2 years and 4 months (median 28 days). Conclusions Children with MAHS have various clinical features and extremely poor treatment outcomes.

Objective To study the efficacy of early treatment via fiber bronchoscope in children with Mycoplasma pneumoniae pneumonia (MPP) complicated by airway mucus obstruction. Methods According to the time from admission to the treatment via fiber bronchoscope, the children with MPP who were found to have airway mucus obstruction under a fiber bronchoscope were randomly divided into early intervention group (≤ 3 days; n=40) and late intervention group (>3 days; n=56). The two groups were compared in terms of clinical data and imaging recovery.The children were followed for 1-3 months. Results Of the 96 children, 38 were found to have the formation of plastic bronchial tree, among whom 10 were in the early intervention group and 28 were in the late intervention group (P=0.01). Compared with the late intervention group, the early intervention group had a shorter duration of fever, length of hospital stay, and time to the recovery of white blood cell count and C-reactive protein (P < 0.05), as well as a higher atelectasis resolution rate (P < 0.05). Compared with the late intervention group, the early intervention group had a higher percentage of children with a ≥ 60% absorbed area of pulmonary consolidation at discharge. After 3 months of follow-up, the early intervention group had a higher percentage of children with a ≥ 90% absorbed area of pulmonary consolidation than the late intervention group (80% vs 55%; P=0.01), and the early intervention group had a lower incidence rate of atelectasis than the late intervention group (P < 0.05). Conclusions Early treatment via fiber bronchoscope can shorten the course of the disease and reduce complications and sequelae in MPP children with airway mucus obstruction.

Objective To explore the predictive value of cord blood 25(OH)D₃[25(OH)D₃] for infantile atopic dermatitis (AD), and to provide a reference for primary prevention of early infantile AD. Methods The neonates born from July to September, 2015 were enrolled. The cord blood samples were collected at birth to measure the level of 25(OH)D₃. Outpatient follow-up was conducted for all the infants at 6 weeks, 3 months, and 6 months after birth. A survey was performed to investigate the incidence of AD. Results A total of 67 neonates completed a 6-month follow-up. The incidence of AD was 34% (23/67), and 91% (21/23) of these cases occurred in the first month after birth. The 23 AD children had a significantly lower cord 25(OH)D₃ level than those without AD (P < 0.05). The children with a cord 25(OH)D₃ level < 30 nmol/L showed a significantly higher incidence of AD than those with a cord 25(OH)D₃ level ≥ 30 nmol/L (P < 0.05). The receiver operating characteristic (ROC) analysis showed that the area under the ROC curve of cord 25(OH)D₃ in predicting AD was 0.648 (standard error:0.075; 95%CI:0.502-0.795). Its sensitivity, specificity, positive predictive value, and negative predictive value were 52.2%, 79.5%, 57.1%, and 76.1%, respectively. Logistic regression analysis showed that low cord 25(OH)D₃ level, preference for seafood during pregnancy, atopic family history, and mixed feeding were risk factors for infantile AD (P < 0.05). Conclusions Cord 25(OH)D₃ level is inversely associated with the risk of infantile AD, but it has a low diagnostic value for this disease.

Objective To study the association between the prevalence of overweight/obesity and copy number variations (CNVs) among Han, Uyghur, and Kazak children in Xinjiang, China. Methods The kindergartens in Ili, Altay, and Karamay in Xinjiang were selected as research sites, and stratified cluster sampling was used to select the children aged 3-7 years. Body height and body weight were measured, and exfoliated buccal mucosa cells were collected. CNVplex^® was used to measure the CNVs of FTO_1, IRX3_1, IRX3_2, MC4R_1, and MC4R_2. Results A total of 603 children were surveyed (307 boys and 296 girls). There were 261 Han children, 194 Uyghur children, and 148 Kazak children. The overweight/obesity rates in Han, Uyghur, and Kazak children were 28.3%, 10.3%, and 31.1%, respectively (P < 0.001). In Kazak children, the CNVs of IRX3_1 and MC4R_2 were associated with overweight/obesity (P < 0.05). The multivariate logistic regression analysis showed that the risk of overweight/obesity in Han and Kazak children was 3.443 times (95%CI:2.016-5.880) and 3.924 times (95%CI:2.199-7.001), respectively, that in Uyghur children. The CNV of IRX3_1 was a risk factor for overweight/obesity (P=0.028, OR=2.251, 95%CI:1.418-5.651). Conclusions The CNV of IRX3_1 is associated with overweight/obesity in Han, Uyghur, and Kazak children, and the association between the CNV of IRX3_1 and overweight/obesity in Kazak children should be taken seriously.

Objective To explore the abilities of verbal and visual-spatial memory in Chinese children with developmental dyslexia. Methods Thirty-two children with developmental dyslexia (aged 8-12 years) and thirty-nine age-and gender-matched normal children were involved in the study. Their verbal short-term and verbal working memories were measured using the digit ordering and the digit span tests, respectively. Their visual-spatial short-term and visual-spatial working memories were examined using the forward and backward block-tapping tests, respectively. Results The DD children scored lower in the digit ordering and the digit span tests than the control children (P < 0.05). The scores for the forward and backward block-tapping tests did not vary between the two groups (P > 0.05). Conclusions The children with DD have the deficits in both verbal short-term memory and verbal working memory.

Objective To investigate the effect of ceftriaxone on the intestinal epithelium and microbiota in mice in the early-life stage, as well as the recovery of the intestinal epithelium and reconstruction of intestinal microbiota in adult mice. Methods A total of 36 BALB/C neonatal mice were randomly divided into control group and experimental group, with 18 mice in each group. The mice in the experimental group were given ceftriaxone 100 mg/kg every day by gavage within 21 days after birth. Those in the control group were given an equal volume of normal saline by gavage. Immunohistochemistry was used to measure the expression of Ki67, Muc2, and ZO-1 in the intestinal epithelium. qPCR and next-generation sequencing were used to analyze the overall concentration and composition of fecal bacteria. Results After 21 days of ceftriaxone intervention, the experimental group had a significant reduction in body weight, a significant reduction in the expression of Ki67 and ZO-1 and a significant increase in the expression of Muc2 in intestinal epithelial cells, a significant reduction in the overall concentration of fecal bacteria, and a significant increase in the diversity of fecal bacteria compared with the control group (P < 0.05). Firmicutes was the most common type of fecal bacteria in the experimental group, and there were large amounts of Staphylococcus and Enterococcus. The experimental group had a certain degree of recovery of the intestinal epithelium, but there were still significant differences in body weight and the structure of intestinal microbiota between the two groups at 56 days after birth (P < 0.05). Conclusions Early ceftriaxone intervention significantly affects the development of the intestinal epithelium and the construction of intestinal microbiota in the early-life stage. The injury of the intestinal microbiota in the early-life stage may continue to the adult stage and affect growth and development and physiological metabolism.

White matter damage, characterized by demyelination due to the damage of oligodendrocyte precursor cells (OPCs), is the most common type of brain damage in preterm infants. Survivors are often subject to long-term neurodevelopmental sequelae because of the lack of effective treatment. In recent years, it has been found that cell transplantation has the potential for the treatment of white matter damage. OPCs are frequently used cells in cell transplantation therapy. With abilities of migration and myelinization, OPCs are the best seed cells for the treatment of white matter damage. Several studies have found that OPCs may not only replace impaired cells to reconstruct the structure and function of white matter, but also inhibit neuronal apoptosis, promote the proliferation of endogenous neural stem cells, and enhance the repairment of the blood-brain barrier. However, the clinical application of OPC transplantation therapy faces many challenges, such as the effectiveness, risk of tumorigenesis and immune rejection. With reference to these studies, this article reviewed the development of myelination, the obtainment of OPCs, the therapeutic mechanism as well as application research, and analyzed the current challenges of OPC transplantation, in order to provide a new direction for clinical treatment of white matter damage in preterm infants.

Acute kidney injury (AKI) is a common complication in the neonatal intensive care unit that causes a high mortality of preterm infants and various chronic kidney diseases in adulthood. Preterm infants have immature development of the kidneys at birth. The kidneys continue to develop within a specific time window after birth. However, due to various factors during pregnancy and after birth, preterm infants tend to develop AKI. At present, serum creatinine and urine volume are used for the assessment of kidney injury, and their early sensitivity and specificity have attracted increasing attention. In recent years, various new biomarkers have been identified for early recognition of AKI. This article reviews the features, risk factors, renal function assessment, and prevention/treatment of AKI of preterm infants, in order to provide a reference for improving early diagnosis and treatment of AKI in preterm infants and long-term quality of life.

Preterm infants are a special group, and related severe neurological, respiratory, and digestive disorders have high disability/fatality rates. Allogeneic cell transplantation may be an effective method for the prevention and treatment of these diseases. At present, animal studies have been conducted for allogeneic cell transplantation in the treatment of hypoxic-ischemic encephalopathy, bronchopulmonary dysplasia, and necrotizing enterocolitis. The main difficulty of this technique is graft-versus-host reaction (GVHR), and successful induction of immune tolerance needs to be achieved in order to solve this problem. This article reviews the research advances in immune tolerance of allogeneic cell transplantation in preterm infants.