Nutritional support during the first week for infants with bronchopulmonary dysplasia and respiratory distress: a multicenter cohort study in China.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major complication affecting the survival rate and long-term outcomes of preterm infants. A large, prospective, multicenter cohort study was conducted to evaluate early nutritional support during the first week of life for preterm infants with a gestational age < 32 weeks and to verify nutritional risk factors related to BPD development. METHODS: A prospective multicenter cohort study of very preterm infants was conducted in 40 tertiary neonatal intensive care units across mainland China between January 1, 2020, and December 31, 2021. Preterm infants who were born at a gestational age < 32 weeks, < 72 h after birth and had a respiratory score > 4 were enrolled. Antenatal and postnatal information focusing on nutritional parameters was collected through medical systems. Statistical analyses were also performed to identify BPD risk factors. RESULTS: The primary outcomes were BPD and severity at 36 weeks postmenstrual age. A total of 1410 preterm infants were enrolled in this study. After applying the exclusion criteria, the remaining 1286 infants were included in this analysis; 614 (47.7%) infants were in the BPD group, and 672 (52.3%) were in the non-BPD group. In multivariate logistic regression model, the following six factors were identified of BPD: birth weight (OR 0.99, 95% CI 0.99-0.99; p = 0.039), day of full enteral nutrition (OR 1.03, 95% CI 1.02-1.04; p < 0.001), parenteral protein > 3.5 g/kg/d during the first week (OR 1.65, 95% CI 1.25-2.17; p < 0.001), feeding type (formula: OR 3.48, 95% CI 2.21-5.49; p < 0.001, mixed feed: OR 1.92, 95% CI 1.36-2.70; p < 0.001; breast milk as reference), hsPDA (OR 1.98, 95% CI 1.44-2.73; p < 0.001), and EUGR ats 36 weeks (OR 1.40, 95% CI 1.02-1.91; p = 0.035). CONCLUSIONS: A longer duration to achieve full enteral nutrition in very preterm infants was associated with increased BPD development. Breastfeeding was demonstrated to have a protective effect against BPD. Early and rapidly progressive enteral nutrition and breastfeeding should be promoted in very preterm infants. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2000030125 on 24/02/2020) and in www.ncrcch.org (No. ISRCTN84167642 on 25/02/2020).

Alteration of the gut microbiota after surgery in preterm infants with necrotizing enterocolitis.

Purpose: To investigate the dynamic changes in the intestinal microbiota in preterm infants with necrotizing enterocolitis (NEC) before and after treatment via a prospective case-control study. Methods: Preterm infants with NEC and preterm infants with similar age and weight (control group) were enrolled in this study. They were divided into NEC_Onset (diagnosis time), NEC_Refeed (refeed time), NEC_FullEn (full enteral nutrition time), Control_Onset, and Control_FullEn groups according to the time of the fecal material collected. Except for basic clinical information, fecal specimens of the infants were obtained as well at indicated times for 16S rRNA gene sequencing. All infants were followed up after discharge from the NICU, and the growth data of the corrected age of 12 months were acquired from the electronic outpatient system and telephonic interviews. Results: A total of 13 infants with NEC and 15 control infants were enrolled. A gut microbiota analysis showed that the Shannon and Simpson indices were lower in the NEC_FullEn group than in the Control_FullEn group (p < .05). Methylobacterium, Clostridium_butyricum, and Acidobacteria were more abundant in infants with NEC during diagnosis. Methylobacterium and Acidobacteria were remained plentiful in the NEC group until the end of treatment. These bacteria species were significantly positively correlated with CRP and negatively correlated with platelet count. The rate of delayed growth was higher in the NEC group than in the control group (25% vs. 7.1%) at 12 months of corrected age, but there was no significant difference. In addition, the pathways of synthesis and degradation of ketone bodies were more active in the NEC subgroups, including both the NEC_Onset group and the NEC_FullEn group. The pathway of sphingolipid metabolism was more active in the Control_FullEn group. Conclusion: Even after reaching the full enteral nutrition period, alpha diversity in infants with NEC who underwent surgery was lower than that in the control group infants. It may take more time to reestablish the normal gut flora of NEC infants after surgery. The pathways of the synthesis and degradation of ketone bodies and sphingolipid metabolism might be related to the pathogenesis of NEC and physical development after the occurrence of NEC.

Home oxygen use and 1-year outcome among preterm infants with bronchopulmonary dysplasia discharged from a Chinese regional NICU.

Objective: This study aims to compare the clinical characteristics and 1-year outcomes of preterm infants with bronchopulmonary dysplasia (BPD) who were discharged on supplemental oxygen or room air. Materials and Methods: The preterm infants (born <32 weeks' gestation, birth weight ≤1,250 g) diagnosed with BPD and admitted between January 2020 and December 2020 were enrolled. The clinical data during hospitalization were collected through the hospital's electronic record system. The outcomes after discharge were acquired from the outpatient system and through telephonic interviews. Results: Of the 87 preterm infants diagnosed with BPD, 81 infants survived until discharge. The 81 infants were divided into the home oxygen group (n = 29) and room air group (n = 52) according to supplemental oxygen or not at discharge. Infants in the home oxygen group were more likely to receive postnatal systemic steroids and higher ventilation settings at 36 weeks' PMA. There was one patient in each group who died before 1 year corrected age, respectively. All the infants had successfully weaned off oxygen eventually during the first year. The median duration of home oxygen therapy was 25 (7,42) days. Readmission occurred in 49 (64.5%) infants. Readmissions for infants with home oxygen were more often related to respiratory disease. In addition, wheezing disorders and home inhalation occurred more frequently in the home oxygen group (p = 0.022, p = 0.004). Although the incidence of underweight at 1 year corrected age was higher in the room air group (10.0 vs. 3.8%), there was no significant difference (p = 0.620). The rate of neurodevelopmental impairment was similar between these two groups (26.0 vs. 30.8%, p = 0.659). Conclusions: It was the first study focused on preterm infants with BPD receiving home oxygen in China. Infants with home oxygen were more likely to have respiratory problems after discharge from NICU. Home oxygen use was not associated with more readmission for infants with BPD, and no difference was found in neurodevelopmental impairment and growth outcome.

[Clinical effect of multi-oil fat emulsion for parenteral nutrition support in extremely low birth weight infants].

OBJECTIVE: To study the clinical effect of multi-oil fat emulsion for parenteral nutrition support in extremely low birth weight (ELBW) infants. METHODS: A retrospective analysis was performed for 49 ELBW infants who were admitted from January 1, 2018 to July 30, 2020, with an age of ≤14 days on admission and a duration of parenteral nutrition of > 14 days. According to the type of lipid emulsion received, the ELBW infants were divided into two groups: soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) (n=26) and medium-chain triglycerides/long-chain triglycerides (MCT/LCT) (n=23). The two groups were compared in terms of clinical features, complications, nutrition support therapy, and outcome. RESULTS: The 49 ELBW infants had a mean birth weight of (892±83) g and a mean gestational age of (28.2±2.3) weeks. There was no significant difference between the two groups in the incidence rates of hemodynamically significant patent ductus arteriosus, intraventricular hemorrhage, neonatal necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia (BPD), grade Ⅲ BPD, sepsis, and pneumonia (P > 0.05). There was also no significant difference in the duration of parenteral nutrition, the age of total enteral nutrition, and head circumference/body length/body weight at discharge between the two groups (P > 0.05). Of all the infants, 22 (45%) had parenteral nutrition-associated cholestasis (PNAC), with 13 (50%) in the SMOF group and 9 (39%) in the MCT/LCT group but there was no significant difference in the incidence of PNAC between the two groups (P > 0.05); however, the infants with PNAC in the SMOF group had significantly lower peak values of direct bilirubin and alanine aminotransferase than those in the MCT/LCT group (P < 0.05). CONCLUSIONS: The application of multi-oil fat emulsion in ELBW infants does not reduce the incidence rate of complications, but compared with MCT/LCT emulsion, SMOF can reduce the severity of PNAC in ELBW infants.

[Long-term prognosis of neonates with necrotizing enterocolitis].

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.

Clinical characteristic comparison of low birth weight and very low birth weight preterm infants with neonatal necrotizing enterocolitis: a single tertiary center experience from eastern China.

PURPOSE: This study aims to understand the clinical characteristics of preterm neonatal necrotizing enterocolitis (NEC) to improve the medical management level. METHODS: The clinical characteristics of preterm NEC infants with low birth weight (LBW, ≥ 1500 g) and very low birth weight (VLBW, < 1500 g) were compared. Then, clinical information, including demographics, surgical interventions and morbidity, were collected. RESULTS: A total of 149 preterm NEC infants (60 with VLBW and 89 with LBW) were enrolled. Their median birth weight and gestational age were 1600 g and 31 weeks, respectively. Respiratory support and surfactant therapy were more frequent in VLBW infants (90% vs. 38% and 75% vs. 21.3%) than in LBW infants. In addition, 70.5% of these infants were fed by formula before the NEC occurred. Prematurity-associated morbidities were significantly higher in VLBW infants. Furthermore, 12.8% of all NEC infants died at discharge, and mortality was more prevalent in VLBW infants (21.7% vs. 6.7%). The most frequently received surgeries were enterostomy (n = 58), primary anastomosis (n = 42), and peritoneal drainage (n = 2). Multifocal, localized and pan-intestinal disease occurred in 77.5%, 19.6% and three infants, respectively. Furthermore, postoperative complications occurred more frequently in VLBW infants. CONCLUSION: The overall mortality was 12.8% for infants who had a larger mean gestational age and birth weight, when compared to that in developed countries. Higher rate of formula feeding might be an important risk factor for NEC development. Furthermore, mortality and morbidities, especially nutrition-associated complications, were more frequent in VLBW infants.

Rapamycin therapy for neonatal tuberous sclerosis complex with cardiac rhabdomyomas: A case report and review.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease that varies greatly in its expression. The current study reports a novel case of TSC caused by a TSC2 mutation (TSC2c.1642_1643insA or TSC2p.K549fsX589), in which multiple cardiac rhabdomyomas were detected by fetal echocardiography in week 31 of pregnancy. The infant was delivered successfully; however, seizures began 16 days following birth. Subsequent genetic tests confirmed a diagnosis of TSC. Rapamycin treatment resulted in regression of cardiac rhabdomyomas and controlled seizures. The current study demonstrates the value of fetal echocardiography in the diagnosis of TSC and suggests that inhibition of the mammalian target of the rapamycin (mTOR) signaling pathway may be considered as a potential antiepileptogenic therapy for neonatal TSC. In addition, it was demonstrated that rapamycin treatment was therapeutically beneficial for preventing disorders caused by abnormal mTOR signaling, such as cancer. According to the literature, cardiac rhabdomyomas, seizures and skin lesions are well established markers for TSC in neonates. MRI scans of the brain and genetic screening of TSC1 and TSC2 genes may facilitate an early diagnosis of TSC.

Mortality and Morbidity of Extremely Low Birth Weight Infants in the Mainland of China: A Multi-center Study.

BACKGROUND: With the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China. METHODS: All infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors. RESULTS: A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization. CONCLUSIONS: Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.

Epstein-Barr virus (EBV) infection in Chinese children: a retrospective study of age-specific prevalence.

BACKGROUND: Epstein-Barr Virus (EBV) is a globally prevalent herpesvirus associated with infectious mononucleosis and many malignancies. The survey on EBV prevalence appears to be important to study EBV-related diseases and determine when to administer prophylactic vaccine. The purpose of this retrospective study was to collect baseline information about the prevalence of EBV infection in Chinese children. METHODOLOGY/PRINCIPAL FINDING: We collected 1778 serum samples from healthy children aged 0 to 10, who were enrolled in conventional health and nutrition examinations without any EBV-related symptom in 2012 and 2013 in North China (n = 973) and South China (n = 805). We detected four EBV-specific antibodies, i.e., anti-VCA-IgG and IgM, anti-EBNA-IgG and anti-EA-IgG, by ELISA, representing all of the phases of EBV infection. The overall EBV seroprevalence in samples from North and South China were 80.78% and 79.38% respectively. The EBV seropositivity rates dropped slightly at age 2, and then increased gradually with age. The seroprevalence became stabilized at over 90% after age 8. In this study, the seroprevalence trends between North and South China showed no difference (P>0.05), and the trends of average antibody concentrations were similar as well (P>0.05). CONCLUSIONS/SIGNIFICANCE: EBV seroprevalence became more than 50% before age 3 in Chinese children, and exceed 90% after age 8. This study can be helpful to study the relationship between EBV and EBV-associated diseases, and supportive to EBV vaccine development and implementation.

[Predicting outcome in necrotizing enterocolitis with the score for neonatal acute physiology: a retrospective study of 62 cases].

OBJECTIVE: To explore the value of the score for neonatal acute physiology (score for neonatal acute physiology, SNAP) in predicting outcome and risk of surgery of necrotizing enterocolitis (NEC). METHOD: A total of 62 NEC patients in neonatal intensive care unit (NICU) of Zhejiang University Children's Hospital were reviewed from October 2001 to October 2011. All the patients were classified into surgery group and non-surgery group according to whether the patient had the surgical intervention. Also the patients were divided into death group and alive group according to the outcome. Data on gestational age at birth, gender, birth weight, early clinical manifestations, treatment and prognosis of all patients were collected. SNAP-II and score for neonatal acute physiology and perinatal extension II (SNAPPE-II) were calculated on the day of diagnosis. RESULT: Abdominal distension, which was seen in 91.9% of the cases, was the commonest early clinical manifestation. The next was residual and bloody stool. SNAP-II and SNAPPE-II score in surgery group (26.5,26.5) were higher than that of the non-surgery group (13.0, 13.0,P = 0.002, 0.006). And the same scores in death group (29.0,32.0) were higher than those in the alive group (8.0, 8.0) (P = 0.000, 0.000). Measuring the scores as a predictor of surgery, the area under ROC curve for SNAP-II was 0.745, and was 0.714 for SNAPPE-II. The area under ROC curve for SNAP-II was 0.916, and was 0.929 for SNAPPE-II.The best positive point of SNAP-II and SNAPPE-II for predicting surgery was 22 and 28. The best positive point of SNAP-II and SNAPPE-II for predicting death was 18.5 and 22. CONCLUSION: The SNAP-II and SNAPPE-II score may be used to predict the prognosis and the risk of surgery in the NEC patients. The scores are also good predictors of mortality in the early period when NEC occurs.

[Infantile polycystic kidney disease: a case report and literature review].

OBJECTIVE: To summarize the clinical characteristics, diagnosis, treatments and outcomes of perinatal autosomal recessive polycystic kidney disease. METHODS: The clinical data of one case with infantile polycystic kidney disease diagnosed in perinatal stage and the reports of 11 cases seen in the past 15 years searched in Pubmed, OVID and Elsevier and CNKI, Wanfang database by using the polycystic kidney disease, infant, perinatal, autosomal recessive and case report as keyword were reviewed and analyzed. RESULTS: The infant was characterized by huge kidneys, severe respiratory and renal compromise. The kidneys were symmetrically enlarged and highly echogenic by ultrasonographic examination and showed high-signal intensity on T2-weighted images by MRI. Histologic analysis showed pulmonary hypoplasia, numerous dilated and elongated tubular structures in the kidney and dilated intrahepatic biliary ducts. Among the 12 cases, 8 cases' presumptive diagnosis was made by prenatal ultrasound revealed enlarged kidneys and oligohydramnios. All cases suffered respiratory distress after birth, and 5 cases complicated pneumothorax. 6 cases died in neonatal stage because of respiratory failure.1 case died 2 m after birth because of renal failure. Five cases are alive and underwent dialysis, nephrectomy or renal transplant. CONCLUSION: Newborn infants with perinatal autosomal recessive polycystic kidney disease often have poor outcome and died from respiratory and renal failure. Aggressive respiratory support and renal replacement therapy (including nephrectomy, dialysis and transplantation) may give these infants a favorable outcome.

[Clinical analysis of surgical intervention in the treatment of necrotizing enterocolitis in neonates].

OBJECTIVE: To evaluate the high-risk factors, prognostic factors, and operation time for surgical intervention in the treatment of necrotizing enterocolitis (NEC) in neonates. METHODS: Sixty-two NEC neonates who received treatment in the neonatal intensive care unit from October 2001 to October 2011 were enrolled. Patients were assigned to surgery (n=20) and non-surgery groups (n=42). The two groups were compared with respect to general data, complications, clinical symptoms, laboratory examination results, treatment and prognosis. RESULTS: Compared with non-surgery group, the surgery group had significantly higher rates of respiratory distress syndrome, gurgling sound disappearance, C-reactive protein increase, platelet count decrease, positive blood culture, pneumoperitoneum and fixed intestinal loop on X-ray, and mechanical ventilation (P<0.05). Cured patients in the surgery group had significantly lower rates of circulation failure and multiple bowel perforations than patients who died (P<0.05), as shown by the prognostic factor analysis. Of the 20 patients in the surgery group, 19 (95%) underwent operation within one week after diagnosis of NEC and 15 survived the operation. CONCLUSIONS: There are multiple risk factors in surgical intervention for NEC. Bowel lesions and circulation failure are associated with postoperative prognosis. The operation is usually performed within one week after diagnosis of NEC.

[Value of radiographic assessment scale in necrotizing enterocolitis].

OBJECTIVE: This study was conducted to determine the value of the radiographic assessment scale in the diagnosis of neonatal necrotizing enterocolitis, and as measured by need for surgery. METHODS: A total of 61 neonates were classified into three groups according to the Bell's Staging Criteria: NECⅠ(n=25), NECⅡ(n=11) and NEC Ⅲ(n=25). Data on gestational age at birth, gender, birth weight, clinical manifestations, treatment and prognosis of the patients were collected. Radiographic assessment scale scores were evaluated by a pediatric radiologist. RESULTS: Radiographic assessment scale scores in the NECⅠ, NECⅡand NEC Ⅲ groups were 3.2±1.4, 5.3±1.7 and 8.9±1.7, respectively (P<0.05). The score was highest in the NEC Ⅲ group and lowest in the NECⅠgroup. Based on the different therapies, the NEC Ⅲ group was subdivided into operative and non-operative groups. Radiographic assessment scale scores in the two subgroups were 8.71±1.86 and 9.36±1.21 respectively (P>0.05). Radiographic assessment scale scores in neonates with intestinal perforation (9.6±1.1) were higher than in those with intestinal necrosis (6.8±1.8) (P<0.05). The majority of patients (80%) who underwent operation had radiographic assessment scale scores above 7. The effective rate was 96% and 64% respectively in the NECⅠand the NECⅡ groups. Of the children in the NECⅢ group, the cure rate was 71% in the operative group, and the effective rate was 9% in the non-operative group. CONCLUSIONS: The radiographic assessment scale may be used to evaluate the severity of disease in neonates with NEC. Patients with a score on the radiographic assessment scale above 7 have indications for surgical intervention and have better short-term treatment response rates.

Clinical manifestations of patients with chronic pancreatitis.

BACKGROUND: Recent advances in molecular and genomic technologies and pancreatic imaging techniques provided some insights into genetic, environmental, immunologic, and pathobiological factors for chronic pancreatitis (CP). This study was undertaken to investigate the clinical manifestations of patients with chronic pancreatitis at our hospital. METHODS: The data of the patients with CP who had been treated at our hospital between 1997 and 2004 were analyzed. RESULTS: The major symptoms of the patients with CP were abdominal pain, dyspepsia, loss of weight, diabetes mellitus, pancreatic pseudocyst, steatorrhea, and calcification. Biliary diseases were found to be the first cause of CP in this study; but alcohol abuse was the major cause of CP in men and biliary diseases were the first etiological factors for CP in women. The etiological difference of constituent ratio between men and women was related to alcohol consumption (P<0.01). CONCLUSIONS: During the past 8 years, biliary diseases have been the major etiological factors for CP, but their constituent ratio is decreasing, and the constituent ratio of alcohol abuse is increasing gradually. Alcohol tends to replace biliary diseases as the primary etiological factor for CP.