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.

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.

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.

Comprehensive promotion of perinatal collaboration for extremely preterm infants / 中华围产医学杂志

Extremely preterm infants (EPIs) are extremely immature in organ development, vulnerable to various comorbidities after birth, and may result in high mortality and disability rates. The short- and long-term prognosis of EPIs is closely related to early management. In-depth collaboration between obstetricians and pediatricians is the key to improving their quality of life. Compared to developed countries, there is much to improve in the Chinese mainland, especially in perinatal collaboration. The attitude towards EPI treatment, prenatal prophylaxis, intrauterine transport, delivery room warmth, respiratory management in the delivery room, breastfeeding, family integrated care, cord blood stem cell therapy, and other issues in the field of perinatal collaboration in China is discussed in this article, to promote the collaborative work in related fields further.

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 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.

Development and validation of a risk prediction model for low Apgar scores in extremely premature infants / 中国新生儿科杂志

Objective:To establish a risk prediction model for the occurrence of low 1 min Apgar scores in extremely premature infants (EPIs).Methods:From January 2017 to December 2021, EPIs delivered at our hospital were retrospectively analyzed and randomly assigned into training set group and validation set group in a 7∶3 ratio. 17 clinical indicators were selected as predictive variables and low Apgar scores after birth as outcome variables. Lasso regression and multi-factor logistic regression were used within the training set group to select the final predictors for the final model, and the calibration, distinguishability and clinical decision making curves of the final model were evaluated in the validation set group.Results:A total of 169 EPIs were enrolled, including 117 in the training set group and 52 in the validation set group. 4 indicators including gender, fetal distress, assisted conception and delivery time were selected as the final predictors in the final model. Both the training set group and the validation set group had good calibration curves. The area under the receiver operating characteristic curve (AUC) of the prediction model was 0.731, the sensitivity was 72.2%, the specificity was 60.5% and the AUC of the external validation curve was 0.704. The clinical decision making curve showed that the model had a greater benefit in predicting the occurrence of low Apgar score in EPIs within the threshold of 2% to 75%.Conclusions:The clinical prediction model established in this study has good distinguishability, calibration and clinical accessibility and can be used as a reference tool to predict low Apgar scores in EPIs.

The early use of iNO in extremely premature neonates with refractory hypoxic respiratory failure / 中国新生儿科杂志

Objective:To study the early use of inhaled nitric oxide (iNO) as a rescue therapy in extremely premature infants (EPIs) with refractory hypoxic respiratory failure (HRF).Methods:Between January 2021 and December 2021, EPIs with refractory HRF receiving iNO within the first week of life in our NICU were enrolled. Their clinical characteristics and outcomes were retrospectively analyzed.Results:A total of 11 EPIs were included with 5 males and 6 females. The median gestational age (GA) was 24(22.6, 25.2) weeks. The median birth weight (BW) was 580(490, 770) g. The most common primary diagnoses were moderate/severe respiratory distress syndrome (RDS) (5/11) and early-onset sepsis (3/11). The median age starting iNO therapy was 6.5(4.5, 34.0)h and the median duration of iNO was 24(12, 36)h. The median iNO starting dose was 5(5, 8) ppm and the therapeutic range was 5-20 ppm. Therapeutic efficacy was defined as ≥30% FiO 2 reduction after 6 h of iNO treatment. The treatment was effective in 8 cases. The oxygenation index (OI) decreased more than 10% from baseline 1 h after initiation in 9 patients and in all 11 patients after 12 h of iNO. The reduction of OI was more prominent in EPIs with a higher OI at baseline. Of the 11 patients, 8 survived, 1 died and 2 abandoned further treatments. Conclusions:As an early rescue therapy for EPIs with refractory HRF, iNO can improve oxygenation without obvious short-term adverse effects.

Early death, morbidity and pharmacotherapy in extremely premature and very premature in neonatal intensive care units / Morte precoce, morbidade e farmacoterapia em prematuros extremos e muito prematuros em unidades de terapia intensiva neonatal

Abstract Objectives: to evaluate the evolution of extremely preterm and very preterm infants admitted to neonatal intensive care units, regarding the use of ventilatory support, morbidities, medication use, death, survival and viability. Methods: a non-concurrent cohort study, with 163 very premature and extreme newborns hospitalized in three neonatal intensive care units, during 2016 and 2017. A descriptive analysis of the data obtained from the medical records was performed. The outcomes studied were the use of ventilatory support, morbidities, medication use, death and causes of death. A survival curve was constructed and a viability limit was defined. Results: in the study, 28.2% were extreme and 71.8% were very premature. In this order of subgroups, the need for mechanical ventilation was higher for the extremes (65.2% and 41.0%) and the main diagnosis was early sepsis (78.6% and 82.6). Off-label (60.5% and 47.9%) and off-license (25.3% and 29.0%) medications were used. Most deaths (57.8%) occurred between the extremes, mainly due to septic shock. Survival was lower for the lowest gestational ages and the limit of viability was between 26 and 27 weeks. Conclusions: the main morbidities were from the respiratory system, with high use of off-label and unlicensed medications. Extremes had a greater demand for intensive care in addition to needing more drugs and progressing more to death.

Resumo Objetivos: avaliar a evolução dos prematuros extremos e muito prematuros internados em unidades de terapia intensiva neonatais, quanto ao uso de suporte ventilatório e de medicamentos, óbito, sobrevida e viabilidade. Métodos: estudo de coorte não concorrente, com 163 recém-nascidos muito prematuros e extremos internados em três unidades de terapia intensiva neonatais, durante 2016 e 2017. Realizou-se análise descritiva dos dados obtidos dos prontuários. Os desfechos estudados foram o uso de suporte ventilatório, morbidades, uso de medicamentos, óbito e causas de óbito. Foi construída curva de sobrevivência e delimitado um limite de viabilidade. Resultados: no estudo, 28,2% eram extremos e 71,8% muito prematuros. Nessa ordem de subgrupos, a necessidade de ventilação mecânica foi maior para os extremos (65,2% e 41,0%) e o principal diagnóstico foi sepse precoce (78,6% e 82,6).Medicamentos off-label (60,5% e 47,9%) e sem-licença (25,3% e 29,0%) foramutilizados. A maioria dos óbitos (57,8%) ocorreu entre os extremos, principalmente por choque séptico. A sobrevivência foi menor para as menores idades gestacionais e o limite de viabilidade ficou entre 26 e 27 semanas. Conclusões: as principais morbidades foram do sistema respiratório, com alto uso de medicamentos off-label e sem licença. Extremos tiveram maior demanda de cuidados intensivos além de necessitarem de mais medicamentos e evoluírem mais ao óbito.

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.

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.

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.

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.

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

Trends and ranges of blood pressure during the first 7 days after birth in extremely premature infants / 中国新生儿科杂志

Objective:To study the trends and ranges of blood pressure in extremely premature infants (EPIs) during the first 7 days after birth.Methods:From January 2016 to December 2020, EPIs born in our hospital were retrospectively analyzed. Their blood pressure were monitored using umbilical arterial catheters and no patients needed anti-hypotension treatment. The clinical data of the infants and their mothers, blood pressure data during the first 7 days after birth, clinical outcomes and complications were collected. The trends of blood pressure in untreated EPIs were analyzed and the blood pressure ranges of EPIs of different gestational ages (GA) were established.Results:A total of 145 cases of EPIs were included and their systolic pressure, diastolic pressure and mean blood pressure showed upward trends during 2~168 h after birth ( P<0.001). The diastolic pressure increased significantly within 24 h after birth ( P<0.05), systolic pressure and mean blood pressure increased significantly within 72 h after birth ( P<0.05). Blood pressure increased with age and GA. Conclusions:The blood pressure of EPIs will increase spontaneously during 7 days after birth. The ranges of blood pressure are measured for infants with different GA to provide clinical evidence for blood pressure management of EPIs during early postnatal period.

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.

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.

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.

Risk scoring system for bronchopulmonary dysplasia in very and extremely preterm infants / 中华围产医学杂志

Objective:To investigate the risk factors and establish a risk scoring system for bronchopulmonary dysplasia (BPD) in very and extremely preterm infants.Methods:From December 2013 to December 2018, 254 very and extremely preterm infants with less than 32 weeks of gestation hospitalized for 28 d and above in the Third Staff Hospital of Baotou Steel Group were retrospectively enrolled. According to the diagnostic criteria of BPD, they were divided into　the BPD group ( n=129) or the non-BPD group ( n=125). Clinical data and the risk factors for BPD were analyzed with univariate t-test, Chi-square test, rank-sum test, and multivariate logistic regression analysis. Based on the results, the risk scoring system was evaluated by receiver operating characteristic (ROC) curve, sensitivity, and specificity. Results:Logistic regression analysis showed that gestational age, neonatal respiratory distress syndrome (NRDS), ventilator-associated pneumonia (VAP), and duration of ventilation >7 d were the risk factors for BPD (all P<0.05). When the area under the ROC curve was 0.868 (95% CI: 0.823-0.913, P<0.001) and the maximum Youden index was 0.644, the sensitivity of the scoring systems for BPD was 0.884 (95% CI: 0.812-0.931), and the specificity was 0.760 (95% CI: 0.674-0.830). Conclusions:Gestational age, NRDS, VAP, and prolonged duration of ventilation were the risk factors for BPD. The risk scoring system established has the prediction value on BPD in very and extremely preterm infants.

Current situation and challenges in management of extremely premature infants / 中华围产医学杂志

Extremely premature infants with <28 weeks of gestational age are at higher risk of various complications after birth and have higher mortality and disability rate due to the extremely immature organs. In recent years, with the rapid development of the perinatal medical system and related therapeutic technology, extremely preterm infants' short- and long-term prognosis has been significantly improved. Since the new century, with the rapid social and economic development, the number of treated extremely premature infants and its survival rate in China has also significantly increased. However, compared with the developed countries, the gap still exists. Here we outline the current situation of the management of extremely premature infants in China and abroad and the challenges we faced.