A multicenter epidemiological survey of iNO use in preterm infants in China.

OBJECTIVE: To investigate the use of inhaled nitric oxide (iNO) in hospitalized preterm infants in China over 10 years and its clinical outcomes. METHODS: A total of 616 premature infants who were administered iNO in the Neonatology Departments of 5 Class A tertiary hospitals in China for ten years from January 2013 to December 2022 were included retrospectively. Based on their enrollment periods, the patients were divided into two groups: Group 1 from January 2013 to December 2017 and Group 2 from January 2018 to December 2022, respectively. The perinatal characteristics, short-term clinical outcomes, and mortality rates were compared between these two groups. RESULTS: The utilization of iNO in preterm infants grew annually over the past10 years; the utilization of iNO in Group 2 infants increased approximately one-fold when compared with Group 1 (1.52% vs. 0.80%, p < .001), and the increase was greater in gestational age (GA) < 34 weeks compared with 34-36 weeks preterm infants. Moreover, the iNO usage in Group 1 infants with GA < 34 weeks increased from 1.14% to 2.46% and 0.60% to 0.99% in 34-36 weeks preterm infants (p < .001) in Group 2, respectively. Apart from a smaller GA (32.9 w vs. 33.5 w, p < .001) and birth weight (BW, 1900 g vs. 2141 g, p < .001), the initial [14 parts per million (ppm) versus 10 ppm, p < .001] and maximum (15 ppm vs. 10 ppm, p < .001) doses of Group 2 were larger; however, their recent clinical outcomes did not improve with increasing iNO utilization (p > .05)as compared to Group 1, respectively. Although the overall iNO preterm mortality rates over the past 10 years were 25.8%, the mortality rates for preterm infants at 34-36 weeks were significantly lower than for preterm infants at GA < 34 weeks (15.4% vs. 33.8%, p < .001). Nonetheless, no improvement in mortality was observed in Group 2 preterm infants with GA < 34 weeks for the past 5 years when compared with Group 1 (32.9% vs. 35.8%, p > .05) infants, and significantly lower mortality rates were noticed in preterm infants with 34-36 weeks (11.2% vs. 22.7%, p < .001). Patients with hypoxic respiratory failure (HRF) or persistent pulmonary hypertension of the newborn (PPHN) iNO preterm infants did not show lower mortality rates with the increase of iNO use rate (p > .05). The overall mortality rates of preterm PPHN infants with iNO were lower than that of HRF (20.2% vs. 36.5%, p < .001), while the mortality rates of Group 2 preterm PPHN infants with iNO significantly lower than that of HRF (17.7% vs 36.0%, p < .001). CONCLUSION: The iNO has been extensively used in Chinese preterm infants over the past 10 years, this increase was more significant in preterm infants with GA < 34 weeks. Moreover, preterm infants using iNO have lower GA and BW, larger initial and maximum doses, and more aggressive strategies in the last past 5 years. Although iNO use in preterm infants with GA of 34-36 weeks has significantly reduced mortality, mortality rates and short-term clinical outcomes of iNO in preterm infants <34 weeks of GA has no obvious improvement. Further studies are required to investigate the efficacy and safety of iNO in preterm infants <34 weeks of GA.

[Alterations in the intestinal microbiota of preterm infants with neurodevelopmental impairments: a prospective cohort study]. / ç¥žç»å‘è‚²æŸå®³æ—©äº§å„¿è‚ é“èŒç¾¤å˜åŒ–çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To investigate the difference in intestinal microbiota between preterm infants with neurodevelopmental impairment (NDI) and those without NDI. METHODS: In this prospective cohort study, the preterm infants who were admitted to the neonatal intensive care unit of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from September 1, 2019 to September 30, 2021 were enrolled as subjects. According to the assessment results of Gesell Developmental Scale at the corrected gestational age of 1.5-2 years, they were divided into two groups: normal (n=115) and NDI (n=100). Fecal samples were collected one day before discharge, one day before introducing solid food, and at the corrected gestational age of 1 year. High-throughput sequencing was used to compare the composition of intestinal microbiota between groups. RESULTS: Compared with the normal group, the NDI group had a significantly higher Shannon diversity index at the corrected gestational age of 1 year (P<0.05). The principal coordinate analysis showed a significant difference in the composition of intestinal microbiota between the two groups one day before introducing solid food and at the corrected gestational age of 1 year (P<0.05). Compared with the normal group, the NDI group had a significantly higher abundance of Bifidobacterium in the intestine at all three time points, a significantly higher abundance of Enterococcus one day before introducing solid food and at the corrected gestational age of 1 year, and a significantly lower abundance of Akkermansia one day before introducing solid food (P<0.05). CONCLUSIONS: There are significant differences in the composition of intestinal microbiota between preterm infants with NDI and those without NDI. This study enriches the data on the characteristics of intestinal microbiota in preterm infants with NDI and provides reference for the microbiota therapy and intervention for NDI in preterm infants.

[A case report of neonatal severe coronavirus disease 2019]. / æ–°ç”Ÿå„¿é‡åž‹æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Ž1例报告.

A 7-day-old male neonate was admitted due to testing positive for SARS-CoV-2. The neonate was born through cesarian section at 40 weeks and 2 days of gestation. His mother was diagnosed with coronavirus disease 2019 (COVID-19) caused by Omicron variant infection 1 day before delivery. The neonate was separated from his mother after birth and was taken care of by his father. Three days after the neonate was born, his father was also diagnosed with COVID-19. The neonate was diagnosed with COVID-19 on day 7 of life. The neonate presented with hyperpyrexia, dyspnea, hypoxia, and feeding difficulties, and the chest CT showed the coexistence of consolidation and ground glass-like changes mainly located below the posterior pleura. He was given symptomatic support treatment such as low flow oxygen therapy and posture management after admission. He was cured and discharged after 10 days of hospitalization. This is the first reported case of neonatal severe COVID-19 caused by Omicron variant infection in China. It is necessary to take appropriate protective measures for the neonate to prevent infection when the mother or caregiver of the neonate is a suspected or confirmed cases of COVID-19.

Causes of severe neonatal hyperbilirubinemia: a multicenter study of three regions in China.

BACKGROUND: Available evidence suggests that our country bear great burden of severe hyperbilirubinemia. However, the causes have not been explored recently in different regions of China to guide necessary clinical and public health interventions. METHODS: This was a prospective, observational study conducted from March 1, 2018, to February 28, 2019. Four hospitals in three regions of China participated in the survey. Data from infants with a gestational age ≥ 35 weeks, birth weight ≥ 2000 g, and total serum bilirubin (TSB) level ≥ 17 mg/dL (342 µmol/L) were prospectively collected. RESULTS: A total of 783 cases were reported. Causes were identified in 259 cases. The major causes were ABO incompatibility (n = 101), glucose-6-phosphate dehydrogenase deficiency (n = 76), and intracranial hemorrhage (n = 70). All infants with glucose-6-phosphate dehydrogenase deficiency were from the central south region. Those from the central south region had much higher peak total bilirubin levels [mean, 404 µmol/L; standard deviation (SD), 75 µmol/L] than those from the other regions (mean, 373 µmol/L; SD, 35 µmol/L) (P < 0.001). CONCLUSIONS: ABO incompatibility was the leading cause in the east and northwest regions, but cases in the central south region were mainly caused by both ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency, and infants in this region had a much higher peak total bilirubin level. Intracranial hemorrhage may be another common cause. More thorough assessments and rigorous bilirubin follow-up strategies are needed in the central south region.

Correction to: The data and characteristics of the human milk banks in mainland China.

In the original publication of the article, "Hainan province" in Fig 1 was missed out. The corrected Fig. 1 is given below.

Neurodevelopmental outcomes of extremely preterm infants in southern China: A multicenter study.

OBJECTIVE: To assess treatment outcomes and associated factors of extremely preterm infants (EPIs) in GuangXi, China. METHODS: This was a retrospective study consisting of 131 eligible cases with gestational age (GA) between 22 and 28 weeks, and infants were followed until 18-24 months. Data including clinical characteristics, perinatal factors and after-birth conditions were collected from the neonatal intensive care unit in 10 hospitals in Guangxi from January 1st 2010 until May 31st 2016. RESULTS: During that period, 307 EPIs were born in the hospitals. 137 infants died in hospital after their parents decided to withdraw clinical treatment, and 11 infants died despite full resuscitation was provided. Of the 159 surviving infants, 28 infants were lost to follow-up. In total, 131 infants who survived and were presented to follow-up at 18-24 months of age were enrolled into this study. Of the 131 infants evaluated at 18-24 months follow-up, 47 (35.9%) were diagnosed with neurodevelopmental disability (ND), and 84 (64%) demonstrated on tract motor and language skills. The incidence of chorioamnionitis, early onset sepsis (EOS), bronchopulmonary dysplasia (BPD) were all higher in the group of infants who were diagnosed with ND compared to those with normal motor language development (NML), the duration of mechanical ventilation (MV) was longer in ND group, and the higher incidence of ND was seen in the smaller GA babies (p < 0.05). Adjusted the BPD severity, GA was a protective factor of neurodevelopmental outcome (combined OR = 0.338, 95% CI: 0.145-0.791). In EPIs with moderate BPD and severe BPD, chorioamnionitis was a risk factor of ND (OR = 10.313 and 5.778，respectively, 95% CI: 1.389-6.486 and 1.444-23.119, respectively). The Logistic regression analysis showed that GA (OR = 0.207, 95%CI = 0.047-0.917) was a protective factor for ND, and chorioamnionitis (OR = 6.010, 95%CI: 1.331-27.138), moderate-to-severe BPD (OR = 4.285, 95%CI: 1.495-12.287), the duration of MV (OR = 3.508, 95%CI: 2.077-5.926) were independent risk factors for ND in EPIs. CONCLUSIONS: Chorioamnionitis, moderate-to-severe BPD, and the duration of MV were associated with neurodevelopmental disability in EPIs. The smaller the GA, the higher incidence of neurodevelopmental disability.

The data and characteristics of the human milk banks in mainland China.

BACKGROUND: Human milk banks (HMB) have been established for over 100 years in North America and Europe. This study aimed to describe and summarize the operation and characteristics of the HMBs in mainland China since the first nonprofit HMB operated in 2013. METHODS: Operation of HMB in mainland China is based on the standards and guidelines of the Human Milk Banking Association of North America and some countries in Europe and was modified to meet the needs and circumstances in China such as donation only in the local HMB by medical staff. We reviewed the descriptive data of these 14 HMBs and the clinical characteristics of recipients, the eligible milk donors and the donor milk retrospectively. RESULTS: In mainland China, from March 2013 to December 2016, 14 nonprofit HMBs were developed and operational in public hospitals except one and located in the south, east, north and northwest of mainland China. In total, 2680 eligible donors donated 4608.2 L of breast milk. The mean age of these donors was 29.4 years with 60.6% receiving college education and 90.6% term delivery. A total of 4678 recipients including preterm infants (n = 2990, 63.9%), feeding intolerance (n = 711, 15.2%), maternal illness (n = 345, 7.4%), serious infection (n = 314, 6.7%), necrotising enterocolitis (n = 244, 5.2%), post-surgery (n = 38, 0.8%) and others (n = 36, 0.8%). The rate of discarded raw milk was only 4.4% because of hepatitis B and C or cytomegalovirus positivity. CONCLUSIONS: HMB has been developing rapidly in mainland China. Donor human milk was used not only for preterm infants but also for other ill children. But the sustainability of milk banking needs proper management and more financial support by relative health authorities and the government.

[Role of donor human milk feeding in preventing nosocomial infection in very low birth weight infants].

OBJECTIVE: To investigate the role of donor human milk in the prevention of nosocomial infection in very low birth weight infants. MeETHODS: A total of 105 hospitalized preterm infants with a very low birth weight were enrolled. They were classified into mother's own milk feeding group, donor human milk feeding group, and preterm formula feeding group, with 35 infants in each group. The three groups were compared in terms of incidence rates of nosocomial infection, necrotizing enterocolitis, and feeding intolerance, time to full enteral feeding, and early growth indices. RESULTS: Compared with the preterm formula feeding group, the donor human milk feeding group and the mother's own milk feeding group had significantly lower incidence rates of nosocomial infection and necrotizing enterocolitis and shorter time to full enteral feeding (P<0.05). There were no significant differences in head circumference, body length, and weight growth velocity among the three groups. CONCLUSIONS: Donor human milk can be used in case of a lack of mother's own milk and may help to reduce nosocomial infection.

Treatment outcomes and associated factors among extremely preterm infants in a major children hospital in Guangxi, China.

BACKGROUND: In developing countries, infant survival rate and long-term outcomes of extremely preterm infants(EPIs) have significantly improved due to advances in perinatal care. The striking gap in the treatment outcome of EPIs between China and the other developed countries was a major concern. To assess treatment outcomes and associated factors among EPIs in Nanning, China. METHODS: This was a perspective study consisting of eligible cases with gestational age between 22 and 28 weeks and infants were followed to 18-24 months of age. Data including clinical characteristics, perinatal factors and after-birth conditions were collected from the neonatal intensive care unit (NICU) in a major women's and children's health hospital in Guangxi Province from January 1st 2010 to February 1st 2015. RESULTS: During that period 79 EPIs were born in the hospital. Twenty-eight infants died in hospital after their parents decided to withdraw clinical treatment. Of the 51 surviving infants, 5 infants were lost to follow-up. Eleven of the 46 infants were evaluated at 18-24 months of age and were diagnosed with neurodevelopmental disability and 35 infants showed normal motor language development. The incidence of intrauterine infection and intraventricular hemorrhage (IVH) grade III were both higher in the group of infants who were diagnosed neurodevelopmental disability than in the group of infants with normal motor language development (p < 0.05). Logistic regression analysis showed that intrauterine infection (OR = 33.290, 95%CI = 2.180-508.351) and IVH grade III (OR = 26.814, 95%CI = 3.631-197.989) were the major risk factors for neurodevelopmental disability in EPIs. CONCLUSIONS: Intrauterine infection and IVH grade III were associated with the neurodevelopmental disability in EPIs.

Necrotizing enterocolitis in low birth weight infants in China: Mortality risk factors expressed by birth weight categories.

BACKGROUND: We retrospectively investigated incidence, morbidity, and mortality of neonatal necrotizing enterocolitis in China, with special emphasis on determining the predictors of necrotizing enterocolitis associated mortality. METHODS: We identified neonates as having necrotizing enterocolitis if they met the accepted diagnostic criterion. Data pertaining to antenatal period, labor and birth, and the postnatal course of illness were collected. Multivariate analysis and logistic regression were used to analyze the risk factors. RESULTS: There were 1167 cases of necrotizing enterocolitis identified from the 95 participating NICUs in mainland China in 2011, with the incidence of 2.50% and 4.53% in LBW (birth weight <2500 g) and VLBW (birth weight <1500 g) infants, respectively. Stage 1, 2 and 3 diseases were noted in 51.1%, 30.3% and 18.6% of cases respectively. The mortality from stage 2 and 3 necrotizing enterocolitis in this cohort was 41.7%. In VLBW infants, the important risk factors for mortality were small for gestation age (OR: 5.02, 95% CI 1.73-14.6; P = 0.003) and stage 3 NEC (OR: 8.09, 95% CI 2.80-23.3, P < 0.001). In moderate LBW infants (birth weight 1500-2499 g), the risk factors identified for mortality were sepsis during hospitalization (OR: 2.59, 95% CI 1.57-4.28, P < 0.001) and stage 3 NEC (OR: 5.37, 95% CI 3.24-8.90; P < 0.001). CONCLUSIONS: Necrotizing enterocolitis remains an important cause of morbidity and mortality in prematurely born neonates in Chinese neonatal units. Awareness of the associated risk factors and appropriate interventions may improve the outcome of necrotizing enterocolitis in different birth weight subgroup.

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.

[Cellular and humoral immunity in preterm infants of different gestational ages].

OBJECTIVE: To investigate the characteristics of immune function in newborn infants of different gestational ages. METHODS: A total of 115 premature infants free of infection between June 1, 2012 and June 1, 2013 were divided into two groups according to their gestational age at birth: early preterm infant group (28-33+6 weeks, n=57) and late preterm infant group (34-36+6 weeks, n=58). Meanwhile, 88 full-term infants (37-41+6 week) were recruited to the control group. Venous blood samples were collected within 24 hours after birth. The percentages of lymphocyte subsets, such as CD3+, CD4+, CD8+, and CD19+ T cells and natural killer (NK) cells were measured by flow cytometry, and the absolute count of each population was calculated using the results from routine blood work. Concentrations of serum IgG, IgA, and IgM were measured by immunoturbidimetry. RESULTS: Both preterm infant groups had significantly higher percentages of CD3+ and CD4+ T cells and CD4+/CD8+ ratio (P<0.05) and significantly lower percentages of CD8+ and CD19+ T cells and NK cells (P<0.05), as compared with the full-term infant group. The absolute counts of total lymphocytes, CD3+, CD4+, CD8+, and CD19+ T cells, and NK cells in both preterm infant groups were significantly lower than those in the full-term infant group (P<0.05), and the above parameters in the late preterm infant group were significantly higher than those in the early preterm infant group (P<0.05). Both preterm infant groups showed significantly lower concentrations of serum IgG than the full-term infant group (P<0.05), while no significant differences in concentrations of serum IgA and IgM were observed between the three groups (P>0.05). CONCLUSIONS: Neonatal gestational age has an effect on cellular and humoral immunity. The immune function gradually improves with increasing gestational age.

[Influencing factors for severity of bronchopulmonary dysplasia in preterm infants].

OBJECTIVE: To explore the influencing factors for the severity of bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: The clinical data of 110 preterm infants who were diagnosed with BPD and had a hospital stay of over 28 days between January 2011 and December 2013 were analyzed. These BPD infants were divided into 3 groups according to the clinical criteria: mild group (n=52), moderate group (n=44), and severe group (n=14). The relationship between the severity of BPD and the gestational age, birth weight, asphyxia, oxygen therapy, pregnancy complications, intrauterine pneumonia and mechanical ventilation was analyzed. RESULTS: The severity of BPD was correlated with the following factors: gestational age, birth weight, prenatal infection, duration of oxygen inhalation with a concentration of >40%, use of mechanical ventilation, parameters and duration of mechanical ventilation, duration of continuous positive airway pressure, adoption of intubation surfactant extubation (INSURE) approach, Ureaplasma urealyticum infection, intrauterine pneumonia and patent ductus arteriosus. Logistic regression analysis indicated that the mechanical ventilator parameter peak inspiratory pressure (OR=1.260, 95%CI: 1.096-1.448) and duration of mechanical ventilation (OR=1.010, 95%CI: 1.005-1.016) were independent risk factors for the severity of BPD, while the INSURE approach was a protective factor (OR=0.208, 95%CI: 0.060-0.923). CONCLUSIONS: The severity of BPD is associated with various factors in preterm infants. The important measures for preventing BPD include avoiding the birth of preterm infants with a very low birth weight, shortening the duration of mechanical ventilation, preventing and reducing pulmonary infections, and applying the INSURE approach.

[Efficacy of inhaled nitric oxide in premature infants with hypoxic respiratory failure].

OBJECTIVE: To investigate the safety and efficacy of low-concentration inhaled nitric oxide (NO) in the treatment of hypoxic respiratory failure (HRF) among premature infants. METHODS: Sixty premature infants (gestational age ≤ 34 weeks) with HRF were randomized into NO and control groups between 2012 and 2013, with 30 cases in each group. Both groups received nasal continuous positive airway pressure (nCPAP) or mechanical ventilation. NO inhalation was continued for at least 7 days or until weaning in the NO group. The general conditions, blood gas results, complications, and clinical outcomes of the two groups were analyzed. RESULTS: The NO group showed significantly more improvement in blood gas results than the control group after 12 hours of treatment (P<0.05). After that, the change in oxygenation status over time showed no significant difference between the two groups (P>0.05). There were no significant differences in total time of assisted ventilation and duration of oxygen therapy between the two groups (P>0.05). The incidence of bronchopulmonary dysplasia (BPD), patent ductus arteriosus, necrotizing enterocolitis, retinopathy of prematurity, and pneumothorax in infants showed no significant differences between the NO and control groups (P>0.05), but the incidence of IVH and mortality were significantly lower in the NO group than in the control group (7% vs 17%, P<0.05; 3% vs 13%, P<0.05). CONCLUSIONS: NO inhalation may improve oxygenation status and reduce the mortality in premature infants with HRF, but it cannot reduce the incidence of BPD and the total time of mechanical ventilation or nCPAP and duration of oxygen therapy. NO therapy may have a brain-protective effect for premature infants with HRF and does not increase clinical complications.

[Effect of anti-midgut-protein-ingredient antibodies of Anopheles stephensi on the oocysts of Plasmodium yoelii].

OBJECTIVE: To observe the inhibitory effect of the antibodies against midgut-protein-ingredient of Anopheles stephensi on the oocysts of Plasmodium yoelii. METHODS: Female An. stephensi mosquitoes raised in laboratory were dissected and the midguts were collected. Eight BALB/c mice were immunized using midgut-protein (100 microg/mouse, 4 times with an interval of 7-10 day). Ten days after the last immunization, blood was taken from mice armpit artery and serum separated. The immune active antigen of the midgut protein was analyzed by Western blotting. Protein with Mr 38 000-50 000 was separated by sephadex filtering and used to immunize 12 BALB/c mice (100 microg/ mouse, 4 times with interval of 7-10 days). PBS control group was established. Seven days after the last immunization, serum antibody was detected by ELISA. When the antibody titer in immunized mice reached > or = 1:2 560, mice in both groups were infected by P. yoelii (about 2 x 10(7) plasmodium-infected RBC) by abdominal injection. The mosquitoes were fed on the infected mice when the number of female gametes was higher than 2 per 10 microscopical fields 3 days later. After 9 days, the mosquitoes were dissected and the amount of oocysts in midgut was counted. RESULTS: Eight protein bands were shown in midgut-protein of An. stephensi by Western blotting and the band of Mr 38 000-50 000-midgut-protein appeared clearer. The infection rate of oocysts in the experiment and control groups were 28.70% (62/216) and 51.09% (47/92) respectively (P<0.05), with an oocyst index of 14.14 (1 541/109) and 26.02 (1 223/47) respectively (P<0.01). CONCLUSIONS: The midgut protein of Anopheles stephensi with Mr 38 000-50 000 has immune activity, and the antibodies against this protein shows an inhibitory effect on the development of oocysts of Plasmodium yoelii.