Clinical characteristics and risk factors of 341 very preterm/very low birth weight infants with bronchopulmonary dysplasia / 中国医师杂志

Objective:To investigate clinical characteristics and potential risk factors of very preterm/very low birth weight infants with bronchopulmonary dysplasia (BPD).Methods:A retrospective epidemiological study was performed in 341 neonates with birth weights<1 500 g or gestational age between 23 + 0 to 31 + 6 weeks, who were born in Foshan Women and Children Hospital and were admitted to neonatal intensive care units (NICU) within 24 hours of birth. These neonates were divided into non-BPD group and BPD group. Clinical characteristics and potential risk factors were comparatively analyzed between groups. Risk factors for BPD were identified by binary logistic regression analysis. Results:Among the total of 341 enrolled neonates, including 255 neonates without BPD and 86 neonates with BPD, the total incidence of BPD was 25.2%. The incidences of BPD in the infants with gestational age of <30 weeks, 30-32 weeks, and >32 weeks, as well as birth weight <1 000 g, 1 000-1 499 g, and ≥1 500 g were 43.8%(63/144), 15.1%(22/146), 2.0%(1/51), 80.0%(36/45), 20.2%(41/203), 9.7%(9/93), respectively. The gestational age, birth weight, the proportion of cesarean section, and extubation rate within 7 days were lower in BPD group than those in non-BPD group [(28.5±2.4)weeks vs (30.7±1.8)weeks, (1 087.9±312.8)g vs (1 418.4±247.9)g, 54.6%(47/86) vs 75.7%(193/255), 57.1%(44/77) vs 90.0%(108/120), all P<0.05]. Compared to the non-BPD group, the proportion of Apgar score of ≤7 points 5 minutes after birth [16.3%(14/86) vs 2.4%(6/255)], postnatal endotracheal intubation rate [62.8%(54/86) vs 27.4%(70/255)], volume of red blood cell transfusion ≥3 times [31.4%(27/86) vs 6.3%(16/255)], pulmonary surfactant (PS) utilization [82.6%(71/86) vs 44.7%(114/255)], rate of conventional mechanical ventilation [89.5%(77/86) vs 47.0%(120/255)], combined with hemodynamically significant patent ductus arteriosus (HsPDA) [34.9%(30/86) vs 8.2%(21/255)], diagnosed with neonatal respiratory distress syndrome (NRDS) [94.2%(81/86) vs 5.9%(15/255)], combined with clinically diagnosed sepsis [17.4%(15/86) vs 7.0%(18/255)], combined with ≥3 stage retinopathy of prematurity (ROP) [20.9%(18/86) vs 2.7%(7/255)] and mortality [10.5%(9/86) vs 0.8%(2/255)], length of conventional mechanical ventilation, duration of oxygen consumption, and length of hospital stays were higher in the BPD group (all P<0.05). The results of multivariate logistic regression analysis showed that small gestational age ( OR=1.285, 95% CI: 1.010-1.633), Apgar score ≤7 points within 5 min of birth ( OR=5.712, 95% CI: 1.411-23.115), mechanical ventilation duration ( OR=1.113, 95% CI: 1.043-1.188) and oxygen duration ( OR=1.139, 95% CI: 1.092-1.188) were high risk factors for the development of BPD, while heavier birth weight ( OR=0.996, 95% CI: 0.994-0.998) was protective factor for BPD. Conclusions:The smaller the gestational age and the lower the birth weight, the higher the incidence of BPD, Apgar score≤7 points within 5 min of birth, long conventional mechanical ventilation time, and long duration of oxygen consumption are the risk factors for BPD. Prevention of premature delivery, reduction of asphyxia at birth, reduction of endotracheal intubation and invasive ventilation duration, and reduction of oxygen use time are effective measures to reduce the occurrence of BPD.

Association between ureaplasma urealyticum colonization in respiratory tract and bronchopulmonary dysplasia in extremely preterm or extremely low birth weight infants / 中华围产医学杂志

Objective:To investigate the association between ureaplasma urealyticum (UU) colonization in the respiratory tract and bronchopulmonary dysplasia (BPD) in extremely preterm or extremely low birth weight infants.Methods:This was a retrospective study involving preterm infants with gestational age <28 weeks or birth weight <1 000 g who was hospitalized in the Neonatal Intensive Care Unit (NICU) of Chengdu Women's and Children's Central Hospital from June 2019 to March 2022. Respiratory tract secretion was collected for UU DNA detection within 24 h after admission. All the participants were divided into the UU-positive or negative groups based on the detection results. Clinical characteristics of the two groups were analyzed using Mann-Whitney U, t-, or Chi-square tests (Fisher exact test). Results:A total of 82 infants were enrolled, including 31 cases (37.8%) in the UU-positive group and 51 patients (62.2%) in the negative group. Among the 30 cases treated with azithromycin in the positive group, 27 (90.0%, 27/30) turned negative after two courses of treatment. The rates of premature rupture of membranes [51.6% (16/31) vs 17.6% (9/51), χ2=10.50] and prenatal antibiotic exposure [71.0% (22/31) vs 47.1% (24/51), χ2=4.47] in the UU-positive group were both higher than those in the UU-negative group (both P<0.05). Multivariate logistic regression analysis showed that premature rupture of membranes ( OR=5.893, 95% CI: 2.016-17.228) and gestational age ( OR=0.663, 95% CI: 0.441-0.999) were independent risk factors for UU colonization (both P<0.05). UU-positive group had a longer duration of oxygen use [ M ( P25- P75), 1 756 h (1 385-2 088 h) vs 1 357 h (1 128-1 656 h), Z=2.98], a longer length of hospital stay [81 d (70-105 d) vs 68 d (59-84 d), Z=3.05], and higher hospitalization costs [(201 574±70 326) yuan vs (161 288±53 412) yuan, t=－2.74] compared to the UU negative group (all P<0.05). The incidence of BPD [74.2% (23/31) vs 47.1% (24/51), χ2=5.80] and retinopathy of prematurity [93.4% (29/31) vs 74.5% (38/51), χ2=4.68] in the UU positive group was higher than those in the UU-negative group (both P<0.05). No significant correlation was found between UU colonization and the severity of BPD ( P>0.05). Conclusion:UU colonization may increase the incidence of BPD, but there was no clear correlation with the severity of BPD.

Clinical features and outcomes at discharge of outborn very preterm infants of different ages after interhospital transfer / 中华围产医学杂志

Objective:To analyze the distribution of ages at the interhospital transfer of outborn very preterm infants in China and to compare their perinatal characteristics and outcomes at discharge and neonatal intensive care unit (NICU) treatment.Methods:A total of 3 405 outborn very premature infants with a gestational age of 24-31 +6 weeks who were transferred to the NICUs of the Chinese Neonatal Network (CHNN) in 2019 were included in this retrospective study. According to the age at transfer, they were divided into three groups: early transfer (≤1 d), delayed transfer (>1-7 d) and late transfer (>7 d) groups. Analysis of variance, t-test, Chi-square test (Bonferroni correction), Kruskal-Wallis test and Wilcoxon rank-sum test were used to compare the general clinical condition, treatment, and outcomes at discharge among the three groups. Results:The median gestational age was 29.7 weeks (28.3-31.0 weeks) and the average birth weight was (1 321.0 ± 316.5) g for these 3 405 infants. There were 2 031 patients (59.6%) in the early transfer group, 406 (11.9%) in the delayed transfer group and 968 (28.4%) in the late transfer group. Infants who received continuous positive airway pressure ventilation and tracheal intubation in the delivery room accounted for 8.4% (237/2 806) and 32.9% (924/2 805), respectively. A total of 62.7% (1 569/2 504) of the mothers received antenatal glucocorticoid therapy and the ratio in the early transfer group was 68.7% (1 121/1 631), which was higher than that in the delayed transfer group [56.1% (152/271), χ2=16.78, P<0.017] and the late transfer group [49.2% (296/602), χ2=72.56, P<0.017]. The total mortality rate of very premature infants was 12.7% (431/3 405), and the mortality rates in the early, delayed and late transfer groups were 12.4% (252/2 031), 16.3% (66/406) and 11.7% (113/968), respectively ( χ2=5.72, P=0.057). The incidences of severe intraventricular hemorrhage, late-onset sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge were all higher in the delayed and late transfer groups than in the early transfer group, respectively. The incidences of retinopathy of prematurity, retinopathy of prematurity requiring treatment and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge in the late transfer group were significantly higher than that in the delayed transfer group (Bonferroni correction, all P<0.017). In the late transfer group, the median age of very premature infants at discharge was 66.0 d (51.0-86.0 d), and the corrected gestational age at discharge was 38.9 weeks (37.1-41.2 weeks), and both were greater than those in the early transfer [48.0 d (37.0-64.0 d), Z=260.83; 36.9 weeks (35.7-38.3 weeks), Z=294.32] and delayed transfer groups [52.0 d (41.0-64.0 d), Z=81.49; 37.4 weeks (36.1-38.7 weeks), Z=75.97] (all P<0.017). Conclusions:Many very premature infants need to be transferred to higher-level hospitals after birth. The later the very premature infants are transferred, the higher the incidence of complications will be. It is suggested that intrauterine or early postnatal transport may improve the prognosis of very premature infants.

Survival rate and short/long-term outcomes of 32 extremely preterm infants born at less than 23 gestational weeks / 中华围产医学杂志

Objective:To summarize the survival rate, complications, and outcomes of 32 periviable extremely preterm infants (PEPIs) born at ≤23 gestational weeks.Methods:This was a retrospective observational study involving PEPIs born at the Shenzhen Maternity & Child Healthcare Hospital from January 1, 2015, to December 31, 2021. Clinical data of all subjects were collected and analyzed. The survival rates of PEPIs born from 2015 to 2019 and 2020 to 2021 were compared. Chi-square (or Fisher's exact) test was used for statistical analysis. Results:(1) During the study period, 32 PEPIs were admitted, accounting for 0.024% (32/132 534) of all newborns born in the same hospital during the study period. The median gestational age of the 32 PEPIs was 23 weeks (21 +4-23 +6 weeks), and the birth weight was 480 g (350-720 g). (2) The survival rate of PEPIs born between 2020 and 2021 was 10/19, which appears to be a trend higher than that between 2015 and 2019 (3/13, χ2=2.79, P=0.095), while the rate of withdrawal of treatment was 8/13 and 3/19, respectively, with a statistically significant difference ( χ2=7.16, P=0.007). (3) Thirteen of the 32 PEPIs survived on discharge, including four born at 22 weeks and nine at 23 weeks. The birth weights of these surviving infants were 300-<400 g in one case, 400-<500 g in five cases, 500-<600 g in four cases, 600-<700 g in one case, and ≥700 g in two cases. (4) The most common complication was moderate and severe bronchopulmonary dysplasia (10/13), followed by retinopathy of prematurity requiring surgical intervention (5/13), patent ductus arteriosus requiring ligation (4/13), late-onset sepsis (2/13), necrotizing enterocolitis (stage Ⅱa or above) (2/13) and grade Ⅲ-Ⅳ intraventricular hemorrhage or periventricular leukomalacia (2/13). The median duration of follow-up was ten months (6-69 months), and motor retardation occurred in three infants. Conclusions:The overall survival rate of PEPIs in our hospital is relatively high, with a lower incidence of complications during hospitalization and relatively better outcome. However, further studies are required for the long-term prognosis in this group of infants.

Current situation and reflection on management of extremely preterm infants / 中华围产医学杂志

The lower limit of preterm birth varies around the world. In China, the lower limit of preterm infants is set at the gestational age of 28 +0-36 +6 weeks or birth weight ≥1 000 g. Extremely preterm infants are defined as neonates born before 28 weeks of gestation by the World Health Organization. With the development of perinatal medicine and the achievements in neonatal care, the survival rate and the short/long-term outcomes of extreme preterm infants have been greatly improved in China. This article reviews the survival rate, mortality/severe disability rate and medical costs of extremely preterm infants, aiming to provide reference for setting the right lower limit of gestational age for preterm births.

Comparison of mortality and survival without major morbidities of very preterm infants with very low birth weight from Japan and Brazil / Comparação entre mortalidade e sobrevida sem morbidades importantes dos recém-nascidos prematuros de muito baixo peso entre o Japão e o Brasil

Abstract Objective: This study was carried out to understand the disparities in mortality and survival without major morbidities among very premature and very low birth weight infants between participating Neonatal Intensive Care Units (NICUs) from the Brazilian Network on Neonatal Research (RBPN) and the Neonatal Research Network of Japan (NRNJ). Methods: Secondary data analysis of surveys by the RBPN and NRNJ was performed. The surveys were conducted in 2014 and 2015 and included 187 NICUs. Primary outcome was mortality or survival without any major morbidity. Logistic regression analysis adjustment for confounding factors was used. Results: The study population consisted of 6,406 infants from the NRNJ and 2,319 from the RBPN. Controlling for various confounders, infants from RBPN had 9.06 times higher adjusted odds of mortality (95%CI 7.30-11.29), and lower odds of survival without major morbidities (AOR 0.36; 95%CI 0.32-0.41) compared with those from the NRNJ. Factors associated with higher odds of mortality among Brazilian NICUs included: Air Leak Syndrome (AOR 4.73; 95%CI 1.26-15.27), Necrotizing Enterocolitis (AOR 3.25; 95%CI 1.38-7.26), and Late Onset Sepsis (LOS) (AOR 4.86; 95%CI 2.25-10.97). Conclusions: Very premature and very low birth weight infants from Brazil had significantly higher odds for mortality and lower odds for survival without major morbidities in comparison to those from Japan. Additionally, we identified the factors that increased the odds of in-hospital neonatal death in Brazil, most of which was related to LOS.

RESUMO Objetivo: Este estudo foi realizado para compreender as disparidades na mortalidade e sobrevivência sem as principais morbidades entre recém-nascidos muito prematuros e de muito baixo peso entre Unidades de Terapia Intensiva Neonatal (UTINs) participantes da Rede Brasileira de Pesquisas Neonatais (RBPN) e Rede de Pesquisa Neonatal do Japão (NRNJ). Métodos: Foi realizada uma análise dos dados secundários dos bancos de dados da RBPN e da NRNJ. As pesquisas foram realizadas em 2014 e 2015 e incluíram 187 UTINs. O desfecho primário foi mortalidade ou sobrevida sem qualquer morbidade importante. Utilizou-se a análise de regressão logística com ajuste para os fatores de confusão. Resultados: A população do estudo foi composta por 6.406 recém-nascidos do NRNJ e 2.319 do RBPN. Ajustando para diversos fatores de confusão, os prematuros da RBPN tiveram 9,06 vezes maiores chances de mortalidade (IC95% 7,30-11,29) e menores chances de sobrevivência sem morbidades importantes (AOR 0,36; IC95% 0,32-0,41) em comparação com os da NRNJ. Fatores associados a maiores chances de mortalidade entre as UTINs brasileiras incluíram: síndrome de escape de ar (AOR 4,73; IC95% 1,26-15,27), enterocolite necrosante (AOR 3,25; IC95% 1,38-7,26) e sepse de início tardio (AOR 4,86; IC95% 2,25-10,97). Conclusões: Os recém-nascidos muito prematuros e de muito baixo peso do Brasil apresentaram chances significativamente maiores de mortalidade e menores chances de sobrevivência sem as principais morbidades em comparação aos do Japão. Além disso, identificamos os fatores que aumentam as chances da morte neonatal no Brasil, sendo a maioria relacionada à sepse tardia.

Development of health-related quality of life and subjective health complaints in adults born extremely preterm: a longitudinal cohort study.

PURPOSE: To study development trajectories to 34 years of age of health-related quality of life (HRQoL) and subjective health complaints in extremely preterm (EP) born subjects with and without disability, and to compare with term-born controls. METHODS: A Norwegian longitudinal population-based cohort of subjects born in 1982-85 at gestational age ≤ 28 weeks or with birth weight ≤ 1000 g and matched term-born controls completed the Norwegian version of the Short Form Health Survey-36 at ages 24 and 34 and the Health Behaviour in School-aged Children-Symptom Checklist at ages 17, 24 and 34 years. Data were analysed by unadjusted and adjusted mixed effects analyses with time by subject group as interaction term. RESULTS: A total of 35/49 (73%) surviving EP-born and 36/46 (78%) term-born controls participated at this third follow-up. EP-born subjects with severe disability reported clinical significant lower mean score in all domains compared to the term-born controls. Healthy EP-born subjects reported significantly lower mean scores for vitality, role emotional and mental health, and significantly higher mean score for total and psychological health complaints compared to term-born controls. There were no significant interactions with age regarding HRQoL and somatic health complaints, while there were significant differences in psychological health complaints; the EP-born scored higher at age 24 and lower at age 34. CONCLUSIONS: EP-born adults at age 34 reported inferior HRQoL versus term-born peers, especially in the mental health domains, indicating that the negative differences observed at 24 years remained unchanged.

Successful treatment of 3 cases of 22-week extremely premature infants / 中国新生儿科杂志

Objective:To review the treatment experience of extremely premature infants (EPIs) with gestational age (GA) <23 weeks.Methods:From January to November 2021, EPIs with GA<23 weeks treated in our hospital was retrospectively analyzed.Results:A total of 3 patients with GA of 22 weeks were reviewed, including 2 boys and 1 girl. Their birth weight (BW) was 450~498 g. The duration of hospitalization was 112~126 d. The treatment included early "gentle" management strategies, respiratory management, anti-infection, patent ductus arteriosus treatment and parenteral + enteral nutrition. All 3 infants were discharged from the hospital without further oxygen therapy. All had satisfying oral feeding with no neurological sequelae on follow-up.Conclusions:Early "gentle" management is the key to successful treatment and good prognosis for EPIs with GA<23w

Surgical repair of gastroschisis complicated by tracheostenosis in a very premature infant / 中华围产医学杂志

We describe the diagnosis and treatment of a very premature female infant with gastroschisis complicated by tracheostenosis. The pregnant woman, whose fetus was diagnosed with gastroschisis by ultrasound at 22 weeks in a local hospital, was admitted to the Second Affiliated Hospital of Wenzhou Medical University at 28 +1 weeks with oligohydramnios. Ultrasound after admission confirmed the previous diagnosis. A live baby girl was born by vaginal breech delivery at 29 +1 weeks after spontaneous rupture of the membranes. Because of the unstable oxygen saturation, the neonate finally received Silo in the delivery room prior to the closure of abdominal fissure 7 d after birth, and during the placement difficult endotracheal intubation was evident. She was diagnosed with having congenital tracheal stenosis via chest CT scans with 3-dimensional reconstruction 3 weeks after birth and received transbronchoscopic balloon dilatation at 3 months after birth. During the 2-year follow-up, she grew well without any complications.

Effects of intervention program from prenatal period to delivery room on outcomes of extremely preterm infants / 中华围产医学杂志

Objective:To analyze the outcomes of extremely preterm infants (EPIs) after the implementation and quality improvement of an intervention program from the prenatal period to delivery room and the factors influencing the mortality of EPIs.Methods:This was a retrospective study involving 185 EPIs admitted to neonatal intensive care unit (NICU) of Chongqing Health Center for Women and Children from July 1, 2014, to June 30, 2021. The intervention program from the prenatal period to delivery room was implemented in our hospital in January 2018, according to which, EPIs who were admitted before this time were grouped as the historical group ( n=45) and those who were admitted after as the program group ( n=140). The survival rate and morbidity of the two groups were analyzed and compared using t test, Mann Whitney U test, and Chi-square test. The factors influencing the mortality of EPIs were analyzed by univariate screening and logistic regression. Results:(1) The median gestational age of these EPIs was 26 +6 weeks, ranging from 23 +3 to 27 +6 weeks, and the median birth weight was 950 g, ranging from 390 g to 1 290 g. (2) After the intervention, the proportion of patients in whom the neonatologists were involved in prenatal consultation, women who received a full course of antenatal corticosteroid and magnesium sulfate, and cesarean delivery as well as the neonatal temperature on admission to NICU all increased significantly [77.1% (108/140) vs 8.9% (4/45); 67.9% (95/140) vs 35.6% (16/45); 67.1% (94/140) vs 48.9% (22/45); 44.3% (62/140) vs 17.8% (8/45); 36.6 ℃ (36.3-36.9 ℃) vs 35.2 ℃ (35.0-35.3 ℃), respectively, χ2 or Z values were 66.41, 14.81, 4.85, 10.17 and－9.34, respectively, all P<0.05]. Both delayed cord clamping (DCC) and nasal continuous positive airway pressure (nCPAP) were included in the intervention program, with implementation rates from zero before to 67.9% (95/140) and 89.3%(125/140), respectively. Compared to the historical group, the proportion of infants with 1-minute Apgar score ≤3, endotracheal intubation in the delivery room or mechanical ventilation within 72 h after birth were decreased in the program group [7.1% (10/140) vs 17.8% (8/45), 37.1% (52/140) vs 73.3% (33/45), 38.6% (54/140) vs 57.8% (26/45), χ2 values were 4.39, 17.96 and 5.12, respectively. all P<0.05]. (3) After the intervention, the overall survival rate of EPIs and that among those with gestational age from 27 to 27 +6 weeks were significantly improved [72.9% (102/140) vs 53.3% (24/45), OR=2.349, P=0.015; 84.1% (53/63) vs 56.6% (13/23), OR=4.077, P=0.007]. Although the incidence of periventricular and intraventricular hemorrhage, late-onset sepsis, and retinopathy of prematurity showed a downward trend, the differences were not statistically significant (all P>0.05) (4) Multivariate logistic regression analysis showed that 1-minute Apgar score ≤3 ( OR=8.890, 95% CI:2.005-39.412), low 5-minute Apgar score ( OR=1.468, 95% CI:1.103-1.953), and higher rate of mechanical ventilation within 72 h ( OR=7.165, 95% CI:2.942-17.449) were independent risk factors for the mortality of EPIs; and using nCPAP in the delivery room ( OR=0.314, 95% CI:0.137-0.719) and birth weight ( OR=0.996, 95% CI:0.993-0.999) were protective factors. Conclusions:Early interventions for EPIs in the prenatal period or the delivery room, the quality improvement program, including intrapartum temperature management, DCC, and nCPAP, is likely to improve the survival rate and outcome of EPIs.

Mycoplasmahominis meningitis in an extremely preterm infant: a case report and literature review / 中华围产医学杂志

Objective:To summarize the clinical characteristics, diagnosis, treatment, and prognosis of neonatal meningitis caused by Mycoplasma hominis. Methods:We present the clinical data, diagnosis and treatment of a premature infant with Mycoplasma hominis meningitis who was admitted to the Department of Neonatology, the Second Affiliated Hospital of Wenzhou Medical University in June 2020. Relevant literature up to May 2021 was retrieved with the strategy of "( Mycoplasma hominis) AND (meningitis OR central nervous system OR cerebrospinal fluid) AND (newborn)" from CNKI, Wanfang, and PubMed database. The clinical manifestations, examinations, diagnosis, treatments and prognosis of cases with complete clinical data were summarized using two-sample rank sum test. Results:A premature female infant at gestational age of 27 +4 weeks presented with repeated low-grade fever and apnea since the 7 days of life. Cerebrospinal fluid testing in a local hospital showed neutrophil-based leukocytosis, which indicated purulent meningitis. However, empiric antibiotic treatment did not improve the infant's condition. The patient was transferred to our hospital due to dyspnea for 32 days and repeated fever for 25 days. Mycoplasma hominis was detected from the cerebrospinal fluid samples using metagenomic next generation sequencing (NGS). Treatment with erythromycin was ineffective, but the patient improved and discharged after changing to chloramphenicol for 18 d without any side effects. A total of 21 English articles were retrieved, and no Chinese literature was retrieved, involving 22 infants. Of the 23 cases including the present case, 14 were preterm, eight were term and one with no available data; 19 were born by vaginal delivery; the median age of onset was 11.0 d ( P25- P75: 7.0-18.0 d). The initial symptoms included fever, convulsions, irritability, and apnea. Blood routine examination showed elevated white blood cell count in ten cases and elevated C-reactive protein in seven cases. In the cerebrospinal fluid testing, white blood cell count increased in 19 cases, protein increased in 20 cases, and glucose decreased in 13 cases. Eight cases were confirmed by 16S RNA polymerase chain reaction amplification technology, seven by serum antibodies test, two cases by culture and microscopic findings, two cases by culture alone, one case by Mycoplasma kit, and one by NGS. The main treatment was the administration of tetracyclines, quinolones, chloramphenicol, lincosamides, etc. (alone or in combination). Two cases improved without using special anti- Mycoplasma drugs. Of the 23 patients, 15 had hydrocephalus, eight had intracranial hemorrhage, four had cerebral ischemic infarction, and two had cerebral abscess. Four cases had good prognosis,16 cases had adverse prognosis, and other three without available data. The median time to start sensitive antibiotic therapy in children with good prognosis was 4.5 d(3.6-5.0 d) after diagnosis, which was earlier than that in children with adverse prognosis [16.8 d (7.0-25.0 d)]( Z=－2.27, P=0.023). Conclusions:Mycoplasma hominis infection has non-specific clinical manifestations and should be considered for infants with intracranial infection that is not responding to empirical antibiotic treatment. NGS is helpful in detecting Mycoplasma hominis and chloramphenicol can be an option for the treatment.

Attitudes of neonatologists towards treatment of extremely preterm infants in China: a cross- sectional survey / 中华围产医学杂志

Objective:To investigate the attitude of neonatologists toward the treatment of extremely preterm infants (EPIs) in China.Methods:A cross-sectional survey was conducted using a questionnaire designed and posted on Wenjuanxing, a web-based survey platform, from June to July 2021. The respondents were neonatal physicians in various provinces and cities in China. The questionnaire covered the basic information, treatment experience and attitude towards EPIs, and opinions on the current definition of the preterm infant in China. The results were described or analyzed using the Chi-square test.Results:A total of 1 066 valid replies were collected. The respondents included 322 males and 744 females, among whom 78.1% (832/1 066) were assistant director physicians or director physicians, 82.8% (882/1 066) were from tertiary hospitals, and 83.0% (885/1 066) had the experiences of treating EPIs. In terms of the attitude toward the treatment of EPIs, 63.0% (672/1 066) of the respondents suggested that the lower limit of gestational age for EPIs requiring active resuscitation should be defined at 25 gestational weeks or less. Moreover, 57.1% (609/1 066) considered that the current domestic definition of preterm infants as 28 gestational age or above was inappropriate, and 75.2% (458/609) considered that the lower limit defined as preterm infants should be 25 gestational weeks or less. Concerning the treatment experience in EPIs, 54.3% (579/1 066) of the respondents suggested that in their hospital, withdrawing treatment in EPIs was common or very common, and 83.3% (888/1 066) considered that the main reason for withdrawing treatment was family members' concerns about the prognosis. Those who hesitated about treating the EPIs accounted for 71.6% (763/1 066), and 83.9% (640/763) hesitated due to the poor prognosis and possible medical disputes. Moreover, 32.7% (349/1 066) of the respondents or their colleagues had been involved in medical disputes about whether to treat EPIs, and 74.8% (797/1 066) believed that the patients should be the decision-maker on whether to treat EPIs or not.Conclusion:Most neonatal physicians in this survey hold a positive attitude toward the treatment of EPIs and believe that the lower limit of gestational age for preterm infants should be lowered. However, a hesitating attitude to the care of EPIs is still common, and uncertainty about the prognosis of EPIs remains a concern.

Progress on management of periviable extremely premature infants / 中华围产医学杂志

Periviable extremely preterm infant (PEPI) refers to preterm infants born on the border of viability, mainly those with gestational age less than 24 weeks or birth weight less than 500 g. PEPI has increased in the past decades, and about half of the survivors live without severe neurodevelopmental impairment. The management of PEPI remains one of the most complex fields in perinatal-neonatal medicine. Active interventions can reduce the risk of morbidity and mortality in PEPI during early life and short-term follow-up after discharge without increasing the risk of neurodevelopmental impairment. Clinical decision-making about PEPI should not be restricted to population-based prenatal data but should mainly be based on postnatal individual characteristics and conditions. Parents should make an informed choice after detailed consultation with their physician. When the prognosis is uncertain, resuscitation and intensive care could be given and reassessed subsequently. Current interventions or treatments of PEPI refer to strategies for infants born at 24-27 gestational weeks, which need to be refined in practice.

Ethical dilemmas and countermeasures in extreme prematurity at the limit of viability / 中华围产医学杂志

Improved life-supporting technology in the neonatal intensive care unit (NICU) has increased the survival rate of the most extremely preterm infants. However, those who survived are at high risk of developing long-term neurodevelopmental adverse outcomes. The implementation and continuation of intensive care may itself constitute the most challenging ethical dilemma faced by NICU professionals. This paper discusses the main ethical dilemmas in the rescue of the most extremely preterm infants and investigates currently feasible countermeasures to provide a reference for NICU professionals.

Multivariable Predictive Models of Death or Neurodevelopmental Impairment Among Extremely Low Birth Weight Infants Using Heart Rate Characteristics.

OBJECTIVE: We hypothesized that a cumulative heart rate characteristics (HRC) index in real-time throughout the neonatal intensive care unit (NICU) hospitalization, alone or combined with birth demographics and clinical characteristics, can predict a composite outcome of death or neurodevelopmental impairment (NDI). STUDY DESIGN: We performed a retrospective analysis using data from extremely low birth weight infants who were monitored for HRC during neonatal intensive care. Surviving infants were assessed for NDI at 18-22 months of age. Multivariable predictive modeling of subsequent death or NDI using logistic regression, cross-validation with repeats, and step-wise feature elimination was performed each postnatal day through day 60. RESULTS: Among the 598 study participants, infants with the composite outcome of death or moderate-to-severe NDI had higher mean HRC scores during their stay in the NICU (3.1 ± 1.8 vs 1.3 ± 0.8; P < .001). Predictive models for subsequent death or NDI were consistently higher when the cumulative mean HRC score was included as a predictor variable. A parsimonious model including birth weight, sex, ventilatory status, and cumulative mean HRC score had a cross-validated receiver-operator characteristic curve as high as 0.84 on days 4, 5, 6, and 8 and as low as 0.78 on days 50-52 and 56-58 to predict subsequent death or NDI. CONCLUSIONS: In extremely low birth weight infants, higher mean HRC scores throughout their stay in the NICU were associated with a higher risk of the composite outcome of death or NDI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00307333.

Preterm birth, stillbirth and early neonatal mortality during the Danish COVID-19 lockdown.

Using provisional or opportunistic data, three nationwide studies (The Netherlands, the USA and Denmark) have identified a reduction in preterm or extremely preterm births during periods of COVID-19 restrictions. However, none of the studies accounted for perinatal deaths. To determine whether the reduction in extremely preterm births, observed in Denmark during the COVID-19 lockdown, could be the result of an increase in perinatal deaths and to assess the impact of extended COVID-19 restrictions, we performed a nationwide Danish register-based prevalence proportion study. We examined all singleton pregnancies delivered in Denmark during the COVID-19 strict lockdown calendar periods (March 12-April 14, 2015-2020, N = 31,164 births) and the extended calendar periods of COVID-19 restrictions (February 27-September 30, 2015-2020, N = 214,862 births). The extremely preterm birth rate was reduced (OR 0.27, 95% CI 0.07 to 0.86) during the strict lockdown period in 2020, while perinatal mortality was not significantly different. During the extended period of restrictions in 2020, the extremely preterm birth rate was marginally reduced, and a significant reduction in the stillbirth rate (OR 0.69, 0.50 to 0.95) was observed. No changes in early neonatal mortality rates were found.Conclusion: Stillbirth and extremely preterm birth rates were reduced in Denmark during the period of COVID-19 restrictions and lockdown, respectively, suggesting that aspects of these containment and control measures confer an element of protection. The present observational study does not allow for causal inference; however, the results support the design of studies to ascertain whether behavioural or social changes for pregnant women may improve pregnancy outcomes. What is Known: • The aetiologies of preterm birth and stillbirth are multifaceted and linked to a wide range of socio-demographic, medical, obstetric, foetal, psychosocial and environmental factors. • The COVID-19 lockdown saw a reduction in extremely preterm births in Denmark and other high-income countries. An urgent question is whether this reduction can be explained by increased perinatal mortality. What is New: • The reduction in extremely preterm births during the Danish COVID-19 lockdown was not a consequence of increased perinatal mortality, which remained unchanged during this period. • The stillbirth rate was reduced throughout the extended period of COVID-19 restrictions.

The Association of Ambient Temperature with Extremely Preterm Births.

INTRODUCTION: Extremely preterm births (EPT), require complex decision making and significant medical interventions. While environmental factors such as ambient temperature extremes have been associated with preterm births, little is known of the environmental associations with EPT births. The objective of this study is to explore whether ambient temperature is associated with increased risk of EPT birth. METHODS: Birth records for 315,226 infants born in Queensland Australia (2007-2015) were matched to average maximum and minimum temperature for the last month of pregnancy. Odds ratios and 95% confidence intervals were calculated using a generalised linear model. Population attributable risk was calculated for a 5% reduction in maximum temperature. RESULTS: Each one degree increase in maximum [aOR 1.03 (95% CI 1.01, 1.05)] and minimum temperature [aOR 1.02 (95% CI 1.01, 1.04)] was associated with an increase in odds for EPT birth. Increased odds for EPT births was found for maternal smoking [aOR 1.46 (95% CI 1.23, 1.72)], increasing plurality [OR 6.38 (95% CI 5.48, 7.42)] and stillbirth [aOR 342.99 (95% CI 295.53, 398.06)]. When stratified by birth status, the association was only found for live births. DISCUSSION: Higher temperatures are associated with small increases in the odds of delivering an infant in the EPT period. The risk may be enhanced for women who smoke during pregnancy. Women at an increased risk of preterm births should be counselled around methods to reduce their exposure to excessive heat.

Heart rate characteristics monitoring and reduction in mortality or neurodevelopmental impairment in extremely low birthweight infants with sepsis.

We questioned whether a heart rate characteristics (HRC) sepsis risk score displayed to clinicians would modify 18-22 month neurodevelopmental outcomes for extremely low birthweight infants who develop sepsis. Infants allocated to HRC display with sepsis had a 12% absolute reduction in the composite outcome of death or neurodevelopmental impairment. TRIAL REGISTRATION: NCT00307333.

Left Vocal Cord Paralysis, Lung Function and Exercise Capacity in Young Adults Born Extremely Preterm With a History of Neonatal Patent Ductus Arteriosus Surgery-A National Cohort Study.

Background: Left vocal cord paralysis (LVCP) is a known complication of patent ductus arteriosus (PDA) surgery in extremely preterm (EP) born neonates; however, consequences of LVCP beyond the first year of life are insufficiently described. Both voice problems and breathing difficulties during physical activity could be expected with an impaired laryngeal inlet. More knowledge may improve the follow-up of EP-born subjects who underwent PDA surgery and prevent confusion between LVCP and other diagnoses. Objectives: Examine the prevalence of LVCP in a nationwide cohort of adults born EP with a history of PDA surgery, and compare symptoms, lung function, and exercise capacity between groups with and without LVCP, and vs. controls born EP and at term. Methods: Adults born EP (<28 weeks' gestation or birth weight <1,000 g) in Norway during 1999-2000 who underwent neonatal PDA surgery and controls born EP and at term were invited to complete questionnaires mapping voice-and respiratory symptoms, and to perform spirometry and maximal treadmill exercise testing. In the PDA-surgery group, exercise tests were performed with a laryngoscope positioned to evaluate laryngeal function. Results: Thirty out of 48 (63%) eligible PDA-surgery subjects were examined at mean (standard deviation) age 19.4 (0.8) years, sixteen (53%) had LVCP. LVCP was associated with self-reported voice symptoms and laryngeal obstruction during exercise, not with lung function or peak oxygen consumption (VO2peak). In the PDA-surgery group, forced expiratory volume in 1 second z-score (z-FEV1) was reduced compared to EP-born controls (n = 30) and term-born controls (n = 36); mean (95% confidence interval) z-FEV1 was -1.8 (-2.3, -1.2), -0.7 (-1.1, -0.3) and -0.3 (-0.5, -0.0), respectively. For VO2peak, corresponding figures were 37.5 (34.9, 40.2), 38.1 (35.1, 41.1), and 43.6 (41.0, 46.5) ml/kg/min, respectively. Conclusions: LVCP was common in EP-born young adults who had undergone neonatal PDA surgery. Within the PDA-surgery group, LVCP was associated with self-reported voice symptoms and laryngeal obstruction during exercise, however we did not find an association with lung function or exercise capacity. Overall, the PDA-surgery group had reduced lung function compared to EP-born and term-born controls, whereas exercise capacity was similarly reduced for both the PDA-surgery and EP-born control groups when compared to term-born controls.