case study respiratory distress syndrome newborn

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We present a 17-day-old term, female baby who was referred to our centre for persistent respiratory distress. She was managed for pneumonia and pneumothorax at the primary care centre. On detailed clinical examination at admission, a possibility of congenital lobar emphysema (CLE) was considered. A CT chest was performed, and diagnosis of CLE was confirmed. The infant was managed with lobectomy. The respiratory distress settled within a few hours after the surgery, and the baby was discharged in stable condition.

neonatal intensive care
paediatric intensive care

https://doi.org/10.1136/bcr-2017-222290

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Contributors AM, GG, AP and NM conceptualised the study. AM and AP wrote the manuscript and did the final corrections. All authors approved the final manuscript before submission.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Patient consent Parental/guardian consent obtained.

Provenance and peer review Not commissioned; externally peer reviewed.

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Published: 07 September 2024

A nationwide survey on the management of neonatal respiratory distress syndrome: insights from the MUNICH survey in 394 Chinese hospitals

Long Chen 1 ,
Yong Ji 2 ,
Rong Ju 3 ,
Jiang-Qin Liu 4 ,
Ling Liu 5 ,
Jingyun Shi 6 ,
Lili Wang 8 ,
Falin Xu 9 ,
Chuanzhong Yang 10 ,
Huayan Zhang 11 , 12 ,
Yuan Shi ORCID: orcid.org/0000-0002-4571-4424 13 &

MUNICH Study Group

Italian Journal of Pediatrics volume 50 , Article number: 168 ( 2024 ) Cite this article

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At present, preterm infants with respiratory distress syndrome (RDS) in China present higher mortality and morbidity rates than those in high-income countries. The aim of this nationwide survey was to assess the clinical management of RDS in China.

A nationwide cross-sectional survey to assess adherence to RDS management recommendations was performed. One neonatologist per hospital was randomly selected. The primary outcome was the key care of RDS management.

Among the 394 participating hospitals, 88·3% were birthing centres. The number of doctors and nurses per bed were 0·27 and 0·72, respectively. Antenatal corticosteroids (any dose) were administered to 90% of the women at risk of preterm birth at < 34 weeks of gestation (90·0% inborn vs. 50·0% outborn, p < 0·001). The median fraction of inspired oxygen (FiO 2 ) for initial resuscitation was 0·30 for babies born at ≤ 32 weeks of gestation and 0·25 for those born at > 32 weeks. T-piece resuscitators were available in 77·8% of delivery rooms (DRs) (tertiary hospitals: 82·5% vs. secondary hospitals: 63·0%, p < 0·001). Surfactant was used in 51·6% of the DRs. Less invasive surfactant administration (LISA) was used in 49·7% of the hospitals (tertiary hospitals: 55·3% vs. secondary hospitals: 31·5%, p < 0·001). Primary non-invasive ventilation was initiated in approximately 80·0% of the patients. High-frequency oscillation ventilation was primarily reserved for rescue after conventional mechanical ventilation (MV) failure. Caffeine was routinely used during MV in 59·1% of the hospitals. Bedside lung ultrasonography was performed in 54·3% of the health facilities (tertiary hospitals: 61·6% vs. secondary hospitals: 30·4%, p < 0·001). Qualified breast milk banks and Family Integrated Care (FICare) were present in 30·2% and 63·7% of the hospitals, respectively.

Conclusions

Significant disparities in resource availability and guidelines adherence were evident across hospitals. Future strategies should address DR facilities and medication access, technical training, staff allocation, and ancillary facility development for a better management of RDS patients in China.

Neonatal respiratory distress syndrome (RDS) is a prevalent pulmonary condition observed in preterm infants, and is primarily linked to insufficient pulmonary surfactant (PS) or underdeveloped lung structures [ 1 , 2 ]. RDS affects approximately 30% of infants born between 28 and 34 weeks of gestation, with the prevalence increasing to approximately 60% for those born before 28 weeks [ 3 ]. The Chinese Neonatal Network (CHNN) reported a survival rate of 87·6%, with 51·8% of infants born at < 32 weeks of gestation surviving without major morbidities [ 4 ]. However, survival rates vary with socioeconomic status. In low- and middle-income countries (LMICs), more than 90% of extremely preterm infants (EPIs, less than 28 weeks of gestation) do not survive beyond the first few days of life, with RDS being one of the most common causes of death, compared with the mortality rate of less than 10% in high-income countries [ 5 ]. Even in high-income countries, critical conditions associated with significant morbidity and mortality still exist in specific high-risk perinatal situations (e.g., specific social or geographic reasons) [ 6 ]. Efforts to standardize RDS management, including prenatal care, stabilization in the delivery room (DR), surfactant administration, and ventilation strategies, have led to the establishment of various guidelines and consensuses [ 7 , 8 , 9 ].

Perinatal and neonatal care in China has significantly progressed, with neonatal mortality rate of 3·1‰ in 2021, closely aligning with the rates in high-income countries [ 10 , 11 ]. Local guidelines and consensuses in China contribute to defining the criteria for RDS care and neonatal intensive care unit (NICU) construction [ 7 , 12 ]. National and regional neonatal networks are actively engaged in fostering quality improvements in participating hospitals [ 4 , 12 , 13 , 14 ]. Additionally, the development of regional neonatal transportation systems development reflects improved management for critically ill neonates.

Nevertheless, numerous lower-tier hospitals in China continue to face challenges in providing timely and effective treatment, particularly for EPIs [ 15 ]. Given the vast size and population of China, the Medical sUrvey of NICU Insight in CHina (MUNICH) was conducted to comprehensively explore current RDS management across the country.

Study design and participants

In China, general hospitals and maternity-child healthcare hospitals are birthing centres where pregnant women give birth. In contrast, all neonates in children’s hospitals are outborn and transferred from birthing centres not only due to respiratory diseases, but also due to other congenital defects or perinatal diseases [ 16 , 17 , 18 ]. Maternity-child healthcare hospitals and children’s hospitals are usually referred to as paediatric specialty hospitals, which provide treatment for children as well as neonates. Physicians may work as specialists in neonatology departments or as paediatricians responsible for both neonates and children.

In China, tertiary hospitals provide high-level specialized medical services to several areas where most high-risk pregnant women and preterm babies are treated. In parallel, secondary hospitals are regional hospitals that provide comprehensive health services to multiple communities. Although most preterm babies born in secondary hospitals are transferred to designated tertiary hospitals, physicians in secondary hospitals may occasionally deal with preterm birth. Cities were categorized into 1st-tier, 2nd-tier, and 3rd-tier and lower-tier cities. 1st-tier and 2nd-tier cities were defined as well-developed cities, including municipalities directly under the Central Government, capital cities, or regional centres (Table S1). Mainland China was stratified according to a traditional seven-region partition (Northeast, North, East, South, Central, Northwest, and Southwest China). The provinces/autonomous regions/centrally administered municipalities in each region are listed in Table S2. Doctors’ titles were divided into chief and associate chief physician and attending and resident physicians.

On the basis of the above background, a nationwide, multicentre, cross-sectional survey was designed. We used the online MedSci database, covering 31 provincial administrative regions, municipalities, and autonomous regions in China, with 95,444 registered doctors. A total of 2,881 hospitals with neonatal units were identified in the MedSci database.

The MUNICH was conducted with stratified convenience sampling according to the different regions and types of hospitals. The sample size was allocated to eligible hospitals in each region, and only one doctor was recruited at each hospital. The adjusted Yamane formula in the equation was used for sample size calculation.

n = sample size

N = population size = 1500

e = the degree of accuracy expressed as a proportion = 0.03

\(\rho\) = the number of standard deviations that would include all possible values in the range of 4

t = t-value for the selected alpha level or confidence level at 99% = 2.58

ɛ = adjust margin of error [(ε = \(\frac{\rho e}{t}\) )]

The estimated effective sample size of 354 participants was required to achieve a 99% confidence interval (CI), assuming a target hospital number of 1500 (200–250 hospitals in each of the seven district regions). The estimated questionnaire response rate was 90%, and 90% of the responses was valid, for a total sample size of 437. Considering the diverse development across various regions in China and the variability in hospital types, a total sample size of 450 cases was selected in this study. 50–70 doctors from public hospitals in each region were planned to be recruited, with a total of 450 doctors in seven regions (nine doctors for the presurvey). The sample was divided into general hospitals, maternity-child healthcare hospitals and children’s hospitals at a ratio of 6:6:1, and into tertiary and secondary hospitals at a ratio of 3:1 in each region (Fig. 1 ). Physicians who worked in the neonatology department of the selected hospitals were randomly chosen. If the first doctor did not respond, a second doctor from the same hospital was contacted. If no doctor in the selected hospital responded, a doctor at a backup hospital was contacted. Data collection spanned from October to December 2022.

Sampling plan and primary outcome of the MUNICH

In line with the principles of the Declaration of Helsinki, the study was approved by the Ethics Committee of the Children’s Hospital of Chongqing Medical University (Approval Number: 2022–376). All the physicians provided informed consent before participating in the survey.

Questionnaire preparation

The questionnaire was collaboratively developed by the MUNICH Study Group, which comprised specialists with extensive expertise in RDS management. The questionnaire, in alignment with established guidelines, underwent rigorous assessment. A preliminary survey involving nine neonatologists was performed to ensure data clarity and precision. The questionnaire was composed of six dimensions: general information (11 questions), prenatal and perinatal conditions (20 questions), non-invasive ventilation (eight questions), invasive ventilation (eight questions), pulmonary surfactant administration (21 questions), and others (15 questions) (Supplemental 1).

Questionnaire distribution and data collection

A third-party online survey platform was used to manage the distribution and collection of questionnaires. Doctors received the questionnaire via a web link or QR code. The exclusion criteria were as follows: (1) survey with the same answer option selected for all questions or answer options selected with apparent regularity (e.g., ABAB or AAAA); (2) surveys for which the respondent failed to follow the instructions for the question or answered outside the scope of the question; and (3) survey responses from doctors at private hospitals and nurses.

Statistical analyses

Categorical data were represented as frequencies (N) and percentages (%), and intergroup differences were assessed via the chi-square test. Continuous data normality was determined via the Shapiro‒Wilk method. Normally distributed continuous data were expressed as the mean ± standard deviation (mean ± SDs) and were analyzed via t tests or analysis of variance. Nonnormally distributed continuous data were presented as the median (median), first quartile (Q1), and third quartile (Q3), with intergroup comparisons conducted via the Mann‒Whitney U test or Kruskal‒Wallis H test. All the statistical tests were two-tailed, adhering to a predetermined significance level of α = 0·05. The average composite score for the ranking questions was calculated as follows: composite score = (Σ frequency × weight)/number of people who answered the question. The frequency was the number of people who chose each option to be ranked in different positions. The weight was determined by the ranking of the options. For example, if there were three options involved, the weight of the first position in the ranking was three, the second was two, and the third was one. Statistical analysis and boxplots were performed via R (Version 4·2·2). All the data were analysed in five dimensions: hospital level, hospital type, city tier, geographical region, and doctor title.

Profiles of the included physicians and hospitals

Of the 449 questionnaires distributed, 398 responses were obtained (nine presurvey questionnaires were not included). Four questionnaires were excluded (two from nurses and two from doctors at private hospitals), resulting in 394 valid responses from 30 provinces across China (Table S1). The response rate was 88·9% (407/458), and 99·0% of the responses were valid (394/398). Among the respondents, 378 were from birthing centres and 16 were from children’s hospitals. Among all the physicians, 97·4% (384/394) were from the neonatology department or neonatal intensive care unit. Tertiary hospitals constituted 60·9% (298/394) of the sample. Further details on the participating doctors and hospitals are provided in Table 1 .

Bed capacity and human resources

The median numbers of NICUs and total beds were 10·0 (5·0, 25·0) and 30·0 (20·0, 50·0), respectively (Table 2 ). Compared with secondary hospitals, tertiary hospitals had more beds (20·0 (12·0, 25·0) vs. 35·0 (22·3, 60·0) beds, p < 0·001). There were more beds in paediatric specialty hospitals than in general hospitals (40·0 (25·0, 80·0) vs. 25·0 (17·0, 40·0) beds, p < 0·001).

The median numbers of doctors per bed and nurses per bed were 0·27 and 0·72, respectively. Paediatric specialty hospitals had higher ratios than general hospitals did (doctors per bed, 0·26 vs. 0·29, p = 0·002; nurses per bed, 0·66 vs. 0·77, p < 0·001). Comparisons of bed capacity and human resources among different regions are shown in Fig. 2 and Table S3.

Variations in human resources among the different geographic regions ( p < 0·05). a Number of beds, b Number of doctors, c Doctors per bed ratio

Main points of RDS care

Antenatal corticosteroids.

Antenatal corticosteroids (any dose) were administered to approximately 90% of the women at risk of preterm birth at < 34 weeks of gestation. Among the 176 hospitals with both outborn and inborn babies, fewer outborn babies than inborn babies received antenatal corticosteroids (50·0% vs. 95·0%, p < 0·001). The reasons for the lack of antenatal corticosteroid use are shown in Fig. S1A, with precipitous labour exhibiting the highest score of 4·64 points.

Delivery rooms

Data related to DRs were obtained from 378 birthing centres.

Oxygen therapy in DRs

Oxygen blenders were present in 82·0% (310/378) of the DRs in the birthing centres. A median fraction of inspired oxygen (FiO 2 ) of 0·30 for babies born at < 28 weeks of gestation, 0·30 for those born at 28–31 weeks of gestation, and 0·25 for those born at > 32 weeks of gestation was used for initial resuscitation. Notably, general hospitals preferred to set higher initial FiO 2 values than maternity-child healthcare hospitals did for preterm babies born between 28–31 weeks of gestation (0·30 (0·30, 0·40) vs. 0·30 (0·25, 0·35), p = 0·023) and > 32 weeks of gestation (0·30 (0·21, 0·40) vs. 0·21 (0·21, 0·30), p = 0·001). The designated lower and upper limits for target oxygen saturation after the first 10 min postnatally were 89% and 95%, respectively. Compared with secondary hospitals, tertiary hospitals exhibited higher limits (88·0%-95·0% vs. 90·0%-95·0%, p < 0·05). The initial FiO 2 and target oxygen saturation limits among the different groups of hospitals are shown in Table 3 .

T-piece resuscitators

T-piece resuscitators (TPRs) were available in 77·8% (294/378) of the DRs (tertiary hospitals: 82·5% vs. secondary hospitals: 63·0%, p < 0·001; general hospitals: 73·9% vs. maternity-child healthcare hospitals: 84·7%, p = 0·015). Forty-eight (48/378, 12·7%) respondents had only bag-valve-mask resuscitators for positive pressure ventilation in their DRs, with equipment deficiency being the most common cause (41/48, 85·4%). In Northwest China, access to TPRs was comparatively better, at a rate of 90·4%, which was significantly higher than the rates in other regions ( p = 0·019) (Table S4).

PS administration in DRs

A total of 195 (51·6%) hospitals could use PS in the DR. Maternity-child healthcare hospitals had greater accessibility to PS than general hospitals did (61·3% vs. 46·1%, p = 0·004). Compared with 3rd tier and below cities, more hospitals in 1st-tier cities and 2nd-tier cities could use PS in the DR (41·8% vs. 64·7% vs. 60·8%, p < 0·001). The inability to obtain surfactant from the hospital pharmacy, lack of reimbursement before birth, and potential refusal to pay for medication (ranking scores: 4·15, 3·64, and 3·01, respectively) were the top three reasons for the absence of PS in the DRs (Fig. S1B).

PS administration

A total of 60·4% of the respondents used FiO 2 (41·6% chose > 0·30, 41·2% > 0·40 and 15·5% > 0·50) as an indicator for PS administration in patients receiving non-invasive ventilation (NIV). PS was routinely administered to patients receiving mechanical ventilation (MV) according to 79·7% of the respondents.

As shown in Table 4 , the INtubation-SURfactant-Extubation (INSURE) method was used in 341 (341/394, 86·5%) hospitals. Moreover, less invasive surfactant administration (LISA) and/or minimally invasive surfactant therapy (MIST) could be used in 49·7% (196/394) of the hospitals. Compared with secondary hospitals, tertiary hospitals presented a greater capacity for LISA/MIST (31·5% vs. 55·3%, p < 0·001). LISA/MIST was utilized in approximately 30·0% of RDS patients receiving NIV in hospitals performing LISA/MIST. Furthermore, feeding tubes were used for LISA/MIST in nearly half (50·5%) of the hospitals, whereas peripheral vein catheters and umbilical venous catheters were available in 28·2% and 19·8% of the hospitals, respectively.

Non-invasive ventilation

NIV was initiated as primary support in approximately 80·0% of the RDS patients (Central China had a higher rate (85·0%) than other regions did, p = 0·013). Continuous positive airway pressure (CPAP) was more frequently used as an initial (ranking score: 5·07 points) and postextubation (ranking score: 4·49 points) support modality than other NIV modes were (Fig. S1C-D).

Mechanical ventilation

Among the different MV modes, synchronized intermittent mandatory ventilation combined with pressure support ventilation and volume guarantee (SIMV + PSV + VG), synchronized intermittent mandatory ventilation combined with pressure support ventilation (SIMV + PSV), and pressure-controlled assist-control combined with volume guarantee (PC-AC + VG) were the top three modes used (ranking scores: 4·47, 4·09, and 3·92 points, respectively) (Fig. S1E). High-frequency oscillation ventilation (HFOV) was employed as a rescue therapy after conventional MV failure by 91·7% of the physicians, whereas only 36·9% chose it as the initial support modality for EPIs (Fig. S1F).

Caffeine therapy

A total of 59·1% (233/394) of the respondents reported routinely using caffein in patients receiving MV, and 29·2% (115/394) of them preferred to initiate caffeine therapy before weaning patients from ventilators. A total of 82·5% (325/394) of the doctors chose to start caffeine treatment as early as possible for preterm babies whose gestational age was less than the median gestational age of 32 weeks and whose birth weight was less than 1500 g.

Bedside lung ultrasound

Bedside lung ultrasound (LUS) was performed in 54·3% (214/394) of the hospitals (Table 4 ). Tertiary hospitals had great access to bedside LUS than secondary hospitals did (61·6% vs. 30·4%, p < 0·001). The primary applications of LUS are shown in Fig. S2. In the 180 hospitals without bedside LUS, lower-tier cities faced ultrasound machine shortages (1st-tier 36·2% vs. 2nd-tier cities 45·0% vs. 3rd-tier and lower-tier cities 61·8%, p = 0·006).

Ancillary facility construction

Only 30·2% (119/394) of the hospitals possessed a qualified breast milk bank equipped to perform testing, sterilization, storage, and distribution. There was a greater proportion of tertiary hospitals than secondary hospitals (33·4% vs. 19·6%, p = 0·011), and there were fewer general hospitals than paediatric specialty hospitals (26·1% vs. 36·6%, p = 0·028). Home-like wards were available in only 36·0% (142/394) of the hospitals, with more paediatric specialty hospitals than general hospitals having these wards (48·4% vs. 28·2%, p < 0·001). Family Integrated Care (FICare) was available in 63·7% of the hospitals. A greater number of tertiary hospitals and paediatric specialty hospitals implemented FICare in their daily care (tertiary hospitals: 67·9% vs. secondary hospitals: 50·0%, p = 0·002). Among all these regions, central China had the highest proportion of these hospitals (81·8%) (Table S4). The comparison data are shown in Table 4 .

Medical insurance

Approximately 90% of RDS patients in the hospitals were eligible for medical insurance reimbursement. The highest percentage (95%) was observed in Central China (Fig. 3 A). The percentage of medical insurance reimbursement expenses concerning overall hospitalization expenses was approximately 60%, with Southern China having the highest proportion at 65% (Fig. 3 B).

Variations in medical insurance among the different geographic regions ( p < 0·05). a Infants with medical insurance, b Insurance reimbursement/hospitalization expenses

The MUNICH is a cross-sectional, nationwide online survey that aimed to provide a comprehensive overview of the current landscape of RDS care by collecting data from 394 neonatologists (hospitals) across China. The survey explored numerous facets of RDS management and concluded that neonatologists in China are well equipped with essential expertise for the effective treatment of RDS patients. As a result, several areas needing further improvement were identified, including low numbers of doctors and nurses per bed, a lower antenatal corticosteroid utilization rate among outborn infants, relatively conservative oxygen therapy use in DRs, less use of the LISA method, insufficient infrastructure support, and considerable inconsistencies in RDS care among hospitals. To our knowledge, this is the first national survey considering various aspects of RDS treatment in China.

In the survey, we observed median doctors per bed and nurses per bed ratios of 0·27 and 0·72, respectively. These figures closely align with previously published data (doctors per bed, 0.26; nurses per bed, 0.70) [ 19 ]. Disparities among different types of hospitals pose additional challenges. Paediatric specialty hospitals, which had more patients, experienced lower staffing ratios for both doctors and nurses. This imbalance may result in increased workload, potentially leading to lower job satisfaction and staff turnover, creating a detrimental cycle. A recent review revealed that the ratio of nurses per bed in neonatology departments in LMICs varies significantly, indicating an insufficient and inequitable distribution of health workers and a heavy workload in LMICs [ 20 ]. Presently, there are no globally accepted recommendations for staffing ratios in neonatology departments. However, UK standards by Bliss suggest that there should be a minimum nurse-to-baby ratio of 1:1 for intensive care [ 21 ]. A 1:1 NICU nursing staffing ratio has been associated with reduced in-hospital mortality, whereas understaffing increases the risk of nosocomial infections in very-low-birth-weight babies [ 21 , 22 ]. Improving staff allocation and reducing imbalances may be pivotal steps in China.

Approximately 90·0% of preterm infants born at < 34 weeks of gestation received antenatal corticosteroids (any dose). The CHNN reported antenatal corticosteroid use in 75·6% of infants born at < 32 weeks of gestation [ 4 ]. In the US, 88·1% of mothers with extremely preterm babies receive antenatal corticosteroids [ 23 ]. Notably, there has been increasing emphasis on antenatal corticosteroid use over time [ 24 , 25 , 26 ]. However, our data highlight a potential concern: a lower antenatal corticosteroid utilization rate among outborn infants, with emergency labour being a primary factor. Therefore, mothers at high risk of preterm birth require systematic pregnancy management and should be transferred to experienced perinatal centres.

Our data revealed that 82·0% of the DRs in the hospitals had an oxygen blender, which was slightly lower than the 91% reported in Europe [ 27 ]. The initial FiO 2 setting was 0·30 for babies born at ≤ 32 weeks of gestation and 0·25 for those born at > 32 weeks of gestation, which appeared more conservative than what has been recommended in guidelines and consensuses [ 7 , 8 ]. Notably, general hospitals tended to have higher initial FiO 2 settings than paediatric specialty hospitals did. Regarding target oxygen saturation after the first 10 min postnatally, tertiary hospitals tended to be more consistent with the guidelines and consensuses than secondary hospitals did (90·0%-95·0% vs. 88·0%-95·0%, p < 0·05). The overall availability rate of TPRs in the DRs was 77·8%. Disparities were identified among hospitals and across regions. Despite the common perception of greater development in East and South China, less developed Northwest China exhibited better leadership in this respect. This could be attributed to the efforts and emphasis placed on the regional neonatal network and neonatal societies in Northwest China. Moreover, only 12% of infants born at < 32 weeks of gestation received CPAP in the DR according to CHNN data, which is significantly lower than 79% reported in European data [ 27 ]. This highlights a substantial gap between possession and utilization, underscoring the urgent need for future TPR promotion and training [ 4 ]. Of the 48 respondents who had only bag-valve-mask resuscitators in the DR, the first step to improvement is to have the right equipment in place.

There are certain inconsistencies concerning where, when, and how to administer PS. Surfactant was not available in the DRs in 48·4% of the birthing centres, and maternity-child healthcare hospitals had greater access to surfactant than general hospitals did. The reasons cited included the inability to obtain surfactant from the hospital pharmacy, lack of reimbursement before birth, and potential refusal by parents to cover the cost of PS. These issues underscore the challenges of medication access in DRs and prenatal communication, necessitating multidisciplinary collaboration for resolution. Doctors have displayed a variety of approaches in which FiO 2 is used as an indicator for PS administration in patients receiving NIV, despite many studies suggesting that a FiO 2 of 0·30 predicts CPAP failure and the need for PS [ 28 , 29 , 30 , 31 , 32 ]. According to our data, 49·7% of the hospitals performed LISA. A previous survey indicated that the LISA adoption rate was 52% in Europe, and a recent survey in Turkey reported that it was 81·6%, emphasizing the growing prevalence of LISA/MIST techniques in recent years [ 33 , 34 ]. In China, the LISA/MIST utilization rate is relatively low, and more training is needed.

The survey revealed significant variations and imbalances among different hospitals, with tertiary hospitals and paediatric specialty hospitals having greater access to advanced medical resources. Less developed regions face more technical barriers, and medical insurance policies vary across different districts. This situation is a result of both socioeconomic and medical factors. Drawing upon the data from the MUNICH, the following inferences can be made: (1) NICU admission criteria for hospitals of various levels and types and centralized management of extremely and very preterm infants or newborns requiring advanced life support are needed. Ideally, in utero transfers can be performed for high-risk pregnant mothers. (2) Training sessions such as DR resuscitation strategies, LISA/MIST techniques, and ventilation strategies are needed. (3) The promotion of ancillary facilities, including qualified breast milk banks, home-like wards, and FICare is needed to enhance medical care in key hospitals. (4) Improvements in medical insurance policies and reimbursement rates are requested to provide solid support for the treatment of preterm infants. Next, we need to work with the Subspecialty Group of Neonatology and CHNN to widely disseminate the latest RDS guidelines and consensuses, and a future survey with a larger sample size is advisable. Today, the paediatricians’ responsibility is not only to heal, but also to promote the child’s well-being (mental, physical and social) [ 35 ]. Through these efforts, it is hoped that neonatologists will be better able to assist families in making the right decisions from a medical, social, political and economic perspective.

This survey has several limitations. First, collecting data online does not ensure the accuracy of the numerical values obtained. Second, discrepancies may arise between the perspectives of physicians and the actual information. Third, the sample size of paediatric specialty hospitals included in this survey was relatively limited, which may restrict the generalizability of the findings to the broader population of neonatal RDS patients. Notably, the sample distribution was not fully aligned with what was planned due to response variations. Moving forward, our next step involves collaborating closely with the Subspecialty Group of Neonatology and CHNN to ensure broad dissemination of the updated RDS guidelines and consensuses. Additionally, an expanded survey with a larger cohort is expected to enrich our insights.

Chinese medical practitioners possess the necessary expertise to address the diverse requirements associated with RDS care effectively. However, certain deficiencies and significant variations exist. Enhancing staff allocation, upgrading DR facilities and medications, overcoming gaps in key techniques, fostering multidisciplinary collaboration, and developing ancillary facilities will contribute to the overall improvement in RDS management.

Availability of data and materials

The datasets generated during and/or analyzed during the current survey are available from the corresponding author upon reasonable request.

Abbreviations

Chinese Neonatal Network

Confidence interval

Continuous positive airway pressure

Delivery room

Extremely preterm infant

Family integrated care

Fraction of inspired oxygen

High-frequency oscillation ventilation

INtubation-SURfactant-Extubation

Less invasive surfactant administration

Low- and middle-income countries

Lung ultrasound

Minimally invasive surfactant therapy

Medical sUrvey of NICU Insight in China

Neonatal intensive care unit

Pressure-controlled assist-control

Pulmonary surfactant

Pressure support ventilation

Respiratory distress syndrome

Synchronized intermittent mandatory ventilation

T-piece resuscitator

Volume guarantee

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Acknowledgements

We would like to thank all the physicians who participated in the MUNICH survey. This survey was supported by Chiesi China. Chiesi China had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

This survey was supported by Chiesi China. Chiesi China had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

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Department of Neonatology, Women and Children’s Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children, No.120 Longshan Road, Yubei District, Chongqing, China

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Department of Neonatology, Shanghai First Maternity and Infant Hospital, No.2699 West Gaoke Road, Pudong District, Shanghai, China

Jiang-Qin Liu

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Department of Neonatology, Gansu Provincial Maternal and Child Care Hospital (Gansu Provincial Central Hospital), No.143 North Qilihe Street, Lanzhou, Gansu, China

Jingyun Shi

Department of Neonatology, The First Hospital of Jilin University, No.1 Xinmin Street, Changchun, Jilin, China

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Department of Neonatology, The Third Affiliated Hospital of Zhengzhou University, No.7, Kangfuqian Street, Erqi District, Zhengzhou, Henan, China

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Chuanzhong Yang

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Huayan Zhang

Division of Neonatology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, USA

Department of Neonatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, No.136 Zhongshan Second Road, Yuzhong District, Chongqing, China

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Contributions

Long Chen: Writing – review & editing, Writing – original draft, Methodology, Data curation, Formal analysis. Yong Ji: Writing – review & editing, Writing – original draft, Investigation, Formal analysis. Rong Ju: Writing – review & editing, Methodology, Data curation, Formal analysis. Jiang-Qin Liu: Writing – review & editing, Methodology, Data curation, Formal analysis. Ling Liu: Writing – review & editing, Methodology, Investigation, Formal analysis. Jingyun Shi: Writing – review & editing, Writing – original draft, Investigation, Formal analysis. Hui Wu: Writing – review & editing, Methodology, Data curation, Supervision/oversight. Lili Wang: Writing – review & editing, Writing – original draft, Data curation, Investigation. Falin Xu: Writing – review & editing, Writing – original draft, Data curation, Formal analysis. Chuanzhong Yang: Writing – review & editing, Conceptualization/design, Methodology, Supervision/oversight. Huayan Zhang: Writing – review & editing, Conceptualization/design, Methodology, Supervision/oversight. Yuan Shi: Writing – review & editing, Conceptualization/design, Methodology, Supervision/oversight. All authors reviewed the results and approved the final version of the manuscript. All the authors contributed equally.

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Chen, L., Ji, Y., Ju, R. et al. A nationwide survey on the management of neonatal respiratory distress syndrome: insights from the MUNICH survey in 394 Chinese hospitals. Ital J Pediatr 50 , 168 (2024). https://doi.org/10.1186/s13052-024-01741-7

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DOI : https://doi.org/10.1186/s13052-024-01741-7

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Epidural analgesia in labour and neonatal respiratory distress: a case-control study

Affiliation.

1 Division of Neonatology, Department of Pediatrics, University of Alberta, , Edmonton, Alberta, Canada.
PMID: 24170528
DOI: 10.1136/archdischild-2013-304933

Background: Epidural analgesia is the commonest mode for providing pain relief in labour, with a combination of bupivacaine and fentanyl most often used in practice.

Objective: To test whether late-preterm and term neonates exposed to opioids in epidural analgesia in labour are more likely to develop respiratory distress in the immediate neonatal period.

Methods: A case-control study was conducted of singleton infants born during January 2006 to December 2010. Cases were neonates ≥34 weeks gestation, who developed respiratory distress within 24 h of life requiring supplemental oxygen ≥2 h and/or positive pressure ventilation in the neonatal intensive care unit. Controls were gestation and site-matched neonates who did not develop any respiratory distress within the same period. The information on exposure to epidural analgesia and on potential confounding variables was obtained from the standardised delivery record, routinely filled out on all women admitted to the labour wards.

Results: In our study, 206 cases and 206 matched controls were enrolled. Exposure to epidural analgesia was present in 146 (70.9%) cases as compared with 131 (63.6%) of the controls. The association between exposure to epidural analgesia and respiratory distress in neonates was statistically significant upon adjustment for all potential confounders (adjusted OR: 1.75, 95% CI 1.03 to 2.99; p = 0.04). When data was separately analysed for term and late-preterm infants, the results were consistent across these subpopulations, showing no interaction effect.

Conclusions: Late-preterm and term infants exposed to maternal epidural analgesia in labour are more likely to develop respiratory distress in the immediate neonatal period.

Keywords: case-control study; epidural analgesia; respiratory distress.

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Neonatology and obstetric anaesthesia. Ward Platt MP. Ward Platt MP. Arch Dis Child Fetal Neonatal Ed. 2014 Mar;99(2):F98. doi: 10.1136/archdischild-2014-305964. Arch Dis Child Fetal Neonatal Ed. 2014. PMID: 24526166 No abstract available.

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Introduction
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Weekly observed and expected counts based on children with and without medical complexity aged 0 to 17 years of age during prepandemic (April 1, 2017, to February 28, 2020) and pandemic (April 1, 2020 to February 28, 2022) periods. Shaded region indicates 1-month washout period (March 2020).

a Variant of concern emergence (Alpha, Delta, Omicron) based on first case in Canada. 32

Relative rate ratios (95% CI) of respiratory hospitalization, intensive care unit admission, and mortality comparing pandemic and prepandemic periods by sex and age categories for (A) children with medical complexity (CMC) and (B) children without medical complexity (non-CMC).

eTable 1. Public Policy Interventions Instituted in Canada During the COVID-19 Pandemic

eTable 2. Description of the Canadian Institute of Health Information Discharge Abstract Database Used in the Study

eTable 3. Pediatric Clinical Classification System (PECCS)

eTable 4. Serious Respiratory Illnesses in Children With and Without Medical Complexity Comparing Pandemic (2020, 2021) to Pre-Pandemic (2017-2019) Periods in Canadian Hospitals (Excluding Quebec) Limiting to Those Illnesses With an Infectious Diagnosis

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Belza C , Pullenayegum E , Nelson KE, et al. Severe Respiratory Disease Among Children With and Without Medical Complexity During the COVID-19 Pandemic. JAMA Netw Open. 2023;6(11):e2343318. doi:10.1001/jamanetworkopen.2023.43318

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Severe Respiratory Disease Among Children With and Without Medical Complexity During the COVID-19 Pandemic

1 The Hospital for Sick Children, Toronto, Ontario, Canada
2 Edwin S.H. Leong Centre for Healthy Children, University of Toronto, Toronto, Ontario, Canada
3 Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada
4 Dalla Lana School of Public Health, The University of Toronto, Toronto, Ontario, Canada
5 Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
6 ICES, Toronto, Ontario, Canada
7 Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
8 Institute of Health, Policy, Management and Evaluation, The University of Toronto, Toronto, Ontario, Canada
9 Department of Anesthesiology and Pain Medicine. The Hospital for Sick Children, Toronto, Ontario, Canada
10 Institute of Medical Science, The University of Toronto, Toronto, Ontario, Canada
11 Provincial Council for Maternal and Child Health
12 Pulmonology Institute, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel
13 Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
14 McMaster University, Canada

Question Did rates and outcomes of severe respiratory illness change during the first 2 years of the pandemic, compared with prepandemic, among children with medical complexity and those without medical complexity?

Findings In this repeated cross-sectional study of 139 078 respiratory hospitalizations in Canada, there were more than 45 000 fewer respiratory hospitalizations, more than 4200 fewer respiratory intensive care unit admissions and, among children with medical complexity, 119 fewer deaths during respiratory hospitalizations than expected in the first 2 years of the pandemic.

Meaning This study’s results suggest the need for evaluation of the effect of public health interventions in reducing circulating respiratory pathogens during nonpandemic periods.

Importance Severe respiratory disease declined during the COVID-19 pandemic, partially due to decreased circulation of respiratory pathogens. However, the outcomes of children with higher risk have not been described using population-based data.

Objective To compare respiratory-related hospitalizations, intensive care unit (ICU) admissions, and mortality during the pandemic vs prepandemic, among children with medical complexity (CMC) and without medical complexity (non-CMC).

Design, Setting, and Participants This population-based repeated cross-sectional study used Canadian health administrative data of children aged younger than 18 years in community and pediatric hospitals during a pandemic period (April 1, 2020, to February 28, 2022) compared with a 3-year prepandemic period (April 1, 2017, to March 31, 2020). The pandemic period was analyzed separately for year 1 (April 1, 2020, to March 31, 2021) and year 2 (April 1, 2021, to February 28, 2022). Statistical analysis was performed from October 2022 to April 2023.

Main Outcomes and Measures Respiratory-related hospitalizations, ICU admissions, and mortality before and during the pandemic among CMC and non-CMC.

Results A total of 139 078 respiratory hospitalizations (29 461 respiratory hospitalizations for CMC and 109 617 for non-CMC) occurred during the study period. Among CMC, there were fewer respiratory hospitalizations in both 2020 (rate ratio [RR], 0.44 [95% CI, 0.42-0.46]) and 2021 (RR, 0.55 [95% CI, 0.51-0.62]) compared with the prepandemic period. Among non-CMC, there was an even larger relative reduction in respiratory hospitalizations in 2020 (RR, 0.18 [95% CI, 0.17-0.19]) and a similar reduction in 2021 (RR, 0.55 [95% CI, 0.54-0.56]), compared with the prepandemic period. Reductions in ICU admissions for respiratory illness followed a similar pattern for CMC (2020: RR, 0.56 [95% CI, 0.53-0.59]; 2021: RR, 0.66 [95% CI, 0.63-0.70]) and non-CMC (2020: RR, 0.22 [95% CI, 0.20-0.24]; RR, 0.65 [95% CI, 0.61-0.69]). In-hospital mortality for these conditions decreased among CMC in both 2020 (RR, 0.63 [95% CI, 0.51-0.77]) and 2021 (RR, 0.72 [95% CI, 0.59-0.87]).

Conclusions and Relevance This cross-sectional study found a substantial decrease in severe respiratory disease resulting in hospitalizations, ICU admissions, and mortality during the first 2 years of the pandemic compared with the 3 prepandemic years. These findings suggest that future evaluations of the effect of public health interventions aimed at reducing circulating respiratory pathogens during nonpandemic periods of increased respiratory illness may be warranted.

The onset of the COVID-19 pandemic and the public health measures instituted to mitigate its spread were associated with a dramatic reduction in circulating respiratory viruses such as respiratory syncytial virus and influenza. 1 - 3 Infections with respiratory viruses are common contributors to pediatric hospitalizations, either directly (eg, pneumonia) or indirectly (eg, asthma exacerbation). 4 - 6 Dramatic reductions in pediatric health care use were noted during the pandemic, due at least in part to the decrease in respiratory viral infections. 7 - 11 Children with medical complexity (CMC) are at risk of severe acute illness from respiratory infections (eg, children with cystic fibrosis, 12 congenital heart disease, 13 or sickle cell disease 14 ). In a Canadian evaluation, children who were admitted with SARS-CoV-2 infections during the early pandemic period often had existing comorbidities including obesity and neurologic impairment. 15 Children with neurologic impairment (NI), which account for 28% of all Canadian CMC, 16 are at particularly high risk due to a number of factors, including impaired cough and airway clearance, respiratory muscle weakness, bronchial hyperactivity, sleep disordered breathing, and risk of aspiration from oral secretions. 17 This may result in CMC having an outsized benefit from this general decrease in burden of circulating viruses. 18 Reports from multiple countries have suggested decreased emergency department visits 7 , 8 and admissions to hospital during the pandemic both for children with and without medical complexity, 9 - 11 but these findings were limited to those reporting solely on children’s hospitals, evaluations during the early pandemic period, and were not denominated on a defined at-risk population. The effect of pandemic-era suppressed respiratory viral transmission on hospitalization, intensive care unit (ICU) admission, and mortality among CMC and children without medical complexity (non-CMC) is unknown.

Understanding the association of the pandemic with health care utilization related to respiratory illnesses among CMC and non-CMC in Canada, a country that instituted relatively stringent public health measures over the first 2 years of the pandemic, 19 may inform our understanding of the potential benefits of nonpharmaceutical interventions (such as masking, 20 reducing contacts, 20 social distancing, 21 and air filtration and purification 22 ) aimed at protecting children at risk of respiratory hospitalizations during seasonal respiratory viral surges (eTable 1 in Supplement 1 ). Our objective was to evaluate changes in respiratory hospitalizations, ICU admission, and mortality among CMC and non-CMC during the pandemic compared with prepandemic. We hypothesized that there would be a larger decrease in severe respiratory hospitalization and ICU admissions among CMC compared with non-CMC, reflecting the use of nonpharmaceutical interventions mitigating illness transmission for those particularly at risk for infections.

This cross-sectional study used a repeated, population-based analysis and followed the Reporting of Studies Conducted Using Observational Routinely-Collected Data (RECORD) reporting guideline. 23 Using data from the Canadian Institutes for Health Information Discharge Abstract Database (CIHI-DAD) between April 1, 2017, and February 28, 2022, we identified all non-newborn hospitalizations to every acute care hospital in Canada (excluding Québec, which accounts for 21% of Canada’s population) among children younger than 18 years of age (eTable 2 in Supplement 1 ). We included all respiratory hospitalizations using the Pediatric Clinical Classification System (PECCS), which categorizes common reasons for hospitalizations into clinically meaningful groupings 24 - 26 (eTable 3 in Supplement 1 ). CMC were identified using the CIHI CMC methodology based on the Feudtner complex chronic condition (CCC) list, 14 adapted for use in Canada 16 , 27 using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Canadian Edition (ICD-10-CA) diagnostic codes and supplemented with high-intensity NI codes. 28 A CMC hospitalization was defined as a child with any CCC or NI diagnosis code recorded in the 5 years before the index hospitalization. 16 , 27 The population of children in Canada (excluding Québec) at the beginning of each year was obtained from Statistics Canada. 29 Assuming temporal stability in the published proportion of Canadian children with CMC (948 per 100 000), 27 we calculated CMC prevalence based on each year’s total pediatric population.

This study received ethics approval from the Hospital for Sick Children research ethics board. Waiver of consent was granted by the research ethics board due to the use of administrative data.

A prepandemic period (April 1, 2017, to March 1, 2020) was used to derive expected hospitalizations, accounting for time trends and seasonality. The pandemic period was divided into two 12-month periods corresponding with the public sector fiscal year (FY) in Canada (April 1 to March 31). We excluded a 1-month washout period (March 2020) at the start of the pandemic, defining the pandemic period as April 1, 2020, to February 28, 2022. Hospitalization data at CIHI is only captured at discharge, so we excluded the last month (March) of FY 2022 to minimize right-censoring.

We identified all hospitalizations among CMC, which we further described based on 4 mutually exclusive diagnostic groups: NI and at least 1 CCC, multiple organ CCC (excluding NI), NI alone, and 1 non-NI CCC. We also identified hospitalizations for respiratory illnesses among children without medical complexity. For each hospitalization, we described hospitalization-level characteristics (length of stay in days, respiratory etiology subdivided into infectious vs noninfectious [eTable 4 in Supplement 1 ], ICU admission, province or territory of hospitalization) and child-level characteristics (sex, age category, mortality, diagnosis code for medical technology [eg, feeding tube 13 ]). Race and ethnicity data were not available in the CIHI-DAD.

We evaluated changes in CMC and non-CMC respiratory hospitalizations, ICU admission, and in-hospital mortality, using a negative binomial regression model comparing prepandemic observed vs pandemic expected weekly event counts, and summarized as rate ratios (RR) by FY 2020 and 2021 offset by the total pediatric population each year. We conducted a sensitivity analysis limiting respiratory hospitalizations for CMC and non-CMC and mortality for CMC to those with PECCS codes corresponding to a clear infectious etiology (eg, bronchiolitis). As sex and age of the child can be associated with illness severity, 30 , 31 we completed an additional analysis stratified on these variables. We assumed that nonoverlapping 95% CIs for group estimates indicated significant differences. All analyses were completed using SAS studio version 9.4 (SAS Institute) from October 2022 to April 2023.

There were 139 078 respiratory hospitalizations (29 461 for CMC and 109 617 for non-CMC) from March 1, 2017, to February 28, 2022 ( Table 1 ). Children younger than 2 years of age were hospitalized most frequently, accounting for 10 271 (34.8%) of CMC and 56 652 (51.7%) of non-CMC hospitalizations. Male children accounted for the majority of respiratory hospitalizations for both CMC (16 291 [55.3%]) and non-CMC (63 659 [58.1%]). The length of stay among CMC was a median (IQR) of 5 (2-12) days for FY 2017 to FY 2019, 6 (2-18) days in FY 2020, and 5 (2-14) days in FY 2021. For non-CMC, the median (IQR) length of stay remained stable during the study (2 [1-3] days). The most common CMC subgroup across the study period were those with 1 non-NI CCC (13 303 [45.2%] of all CMC hospitalizations). Overall, 11 717 (39.8%) of CMC hospitalizations were among children assisted by a medical technology.

A comparison of observed and expected respiratory hospitalizations among CMC and non-CMC is summarized in Figure 1 . 32 Among CMC, compared with prepandemic annual respiratory hospitalization rates of 1385.6 per 10 000, hospitalizations in FY 2020 decreased to 611.4 per 10 000 CMC, corresponding to an annual rate difference of 774.2 per 10 000 CMC and a rate ratio (RR) of 0.44 (95% CI, 0.42-0.46) ( Table 2 ). In FY 2021, hospitalizations decreased to 774 per 10 000 CMC, which corresponded to an annual rate difference of 611 per 10 000 CMC and an RR of 0.56 (95% CI, 0.51-0.62). Among non-CMC, there was an even larger relative reduction in respiratory hospitalizations in FY 2020 compared with prepandemic, decreasing from 52.9 per 10 000 in the prepandemic period to 9.7 per 10 000 in FY 2020, corresponding to an annual rate difference of 43.2 per 10 000 non-CMC, and a RR of 0.18 (95% CI, 0.17-0.19). Respiratory hospitalizations also decreased for non-CMC in FY 2021, with a comparable relative reduction to that observed in CMC (RR, 0.55 [95% CI, 0.54-0.56]). The absolute reduction during the pandemic was 7409 respiratory admissions for CMC and 37 448 for non-CMC.

There was a similar pattern of reduced respiratory ICU admissions in both FY 2020 and FY 2021 for CMC compared with prepandemic. Respiratory ICU admissions for CMC decreased from 441.8 per 10 000 prepandemic to 248.9 per 10 000 (RR, 0.56 [95% CI, 0.53-0.59]) in FY 2020 and 292.7 per 10 000 (RR, 0.66 [95% CI, 0.63-0.70]) in FY 2021. For non-CMC, respiratory ICU admissions prepandemic were 3.8 per 10 000 with a reduction to 0.8 per 10 000 (RR, 0.22 [95% CI, 0.20-0.24]) in FY 2020 and 2.4 per 10 000 (RR, 0.65 [95% CI, 0.61-0.69]) in FY 2021. The absolute reduction of respiratory ICU admissions was 1829 for CMC and 2460 for non-CMC during the pandemic period.

Among CMC, compared with prepandemic (33.8 per 10 000), mortality during respiratory hospitalizations decreased in both FY 2020 (21.2 per 10 000; RR, 0.63 [95% CI, 0.51-0.77]) and FY 2021 (24.2 per 10 000; RR, 0.72 [95% CI, 0.59-0.87]). Mortality was not assessed in the non-CMC population as the incidence was too low to provide stable estimates. The absolute reduction of in-hospital deaths from respiratory illness was 119 among CMC during the pandemic period.

In stratified analyses, among CMC, female children had a larger reduction of respiratory hospitalizations compared with male children (relative rate ratio [RRR], 0.88 [95% CI, 0.80-0.97]), and the same pattern was observed among all groups of children greater than 2 years of age compared with those aged less than 2 years ( Figure 2 ). Among non-CMC, there was a smaller reduction of respiratory hospitalizations among female children vs male children (RRR, 1.42 [95% CI, 1.17-1.73]) and among children aged 2 to 4 years vs those aged younger than 2 years (RRR, 1.63 [95% CI, 1.22-2.19]). A larger relative reduction in these events was observed in children at least 10 years of age.

When limiting respiratory hospitalizations to those from infectious causes, a similar pattern of decreased relative rates was observed (CMC in FY 2021: RR, 0.31 [95% CI, 0.29-0.33]; CMC in FY 2021: RR, 0.48 [95% CI, 0.46-0.50]; non-CMC in FY 2020: RR, 0.15 [95% CI, 0.14-0.16]; non-CMC in FY 2021: RR, 0.51 [95% CI, 0.48-0.54]) (eTable 4 in Supplement 1 ). Among CMC, mortality during respiratory hospitalizations from infectious causes decreased in FY 2020 (RR, 0.45 [95% CI, 0.26-0.77]), but not in FY 2021 (RR, 0.95 [95% CI, 0.64-1.41]).

In this cross-sectional study, we observed decreased respiratory-related hospitalizations, ICU admissions, and mortality during the first 2 years of the pandemic. The relative reduction in acute care use for respiratory illnesses was more substantial among non-CMC than CMC in the first year of the pandemic, but similar in both groups in the second pandemic year. Similar findings were observed when limiting analysis to respiratory hospitalizations with an infectious diagnosis, except for mortality for CMC in FY 2021. Taken together, this degree of serious respiratory illness reduction over the 2 pandemic years corresponds to a decrease in over 44 500 hospitalizations among Canadian children (7409 for CMC, 37 448 for non-CMC), over 4200 ICU admissions (1829 for CMC, 2460 for non-CMC) and a decrease of 119 CMC in-hospital deaths.

Our study expands on previous reports of decreased overall pediatric hospital use during the pandemic. A single center study from Israel reported a comparable 60% reduction in hospitalizations during lockdown, but did not detect differences among individuals with and without preexisting conditions, which may be because they focused solely on a short, intense lockdown period. 33 A larger multicenter study of children’s hospitals in the United States evaluating the early period of the pandemic reported a 14.4% decrease in all-cause hospitalizations among children with NI. 11 Another multicenter study of children’s hospitals in the United States evaluated the first year of the pandemic among CMC and reported a 20% decline in all-cause hospitalizations but did not observe a decline in ICU use. 10 Our study focused specifically on respiratory hospitalizations which may have been associated with greater pandemic-era declines than hospitalizations overall, and extended evaluation to a longer pandemic period, focused on broader groups of CMC, and included all hospital admissions, not just those in children’s hospitals.

The findings of greater relative mitigation of respiratory hospitalizations in non-CMC compared with CMC in FY 2020 was surprising as we expected greater declines among CMC due to their elevated risk. Potential explanations for this observation include the ongoing circulation of other respiratory viruses during the pandemic for which CMC are at particular risk for hospitalization (eg, enterovirus), 34 unavoidable respiratory admissions unrelated to an infection (eg, noninfectious triggers for asthma or aspiration), and the use of nonpharmacologic infection-prevention strategies to reduce infection risk prepandemic among families of CMC. These explanations may also be relevant in understanding why older children who have a baseline lower risk of respiratory hospitalizations 35 were also observed to have greater relative decreases in respiratory admissions during the pandemic. It is important to emphasize that despite the larger attenuation of respiratory hospitalizations among non-CMC in the first pandemic year, given the much higher baseline prevalence of CMC respiratory hospitalizations, the decline observed among CMC is clinically important and was associated with decreased mortality.

To our knowledge, this study is the longest evaluation (2-year pandemic period) comparing CMC with non-CMC respiratory hospitalizations using population-level data published to date. Nevertheless, the study has limitations. First, although we used an algorithm for ascertaining CMC that has been used extensively in Canadian health services research, 27 administrative data are unable to capture important domains of complexity such as family and/or caregiver needs, psychosocial complexity, and functional status; and administrative data were limited to those with previous hospitalization data. Second, we used PECCS respiratory codes that excluded admissions for underlying respiratory conditions that are likely unrelated to viral infections (eg, bronchopulmonary dysplasia). Among the included codes were diagnoses for which hospitalization may or may not be attributed to a viral respiratory infection (eg, asthma exacerbations by infectious or noninfectious triggers), 19 although hospitalization and ICU admission rates did not change when these codes were excluded. Third, we limited capture of COVID-19 diagnoses to those with an additional PECCS respiratory code (eg, pneumonia). Although we may have missed some cases that were misclassified, at the time, 43.2% of Canadian children admitted to hospital with SARS-CoV-2 infections were not admitted because of COVID-19 (they typically had incidental SARS-CoV-2 infection detected during universal screening at hospital admission). 15 Fourth, the data sets used did not include out-of-hospital mortality from respiratory illnesses; however, more than 80% of CMC deaths occur in hospital. 16 Fifth, this study was conducted in Canada, which had less severe outcomes related to COVID-19 than the United States 36 ; this may be due in part to more widespread adoption of public health measures or other factors. For instance, in Ontario, Canada’s most populous province, mandatory masking, daily symptom checks, social distancing, and cohorting were instituted in schools at the start of the 2020 to 2021 school year. 37 Findings may differ in other jurisdictions. Additionally, this study cannot identify causative factors related to the reduction of hospitalization, ICU admissions, and mortality between CMC and non-CMC.

In this cross-sectional study, we observed decreased hospitalizations and ICU admissions related to respiratory illnesses for both CMC and non-CMC during the COVID-19 pandemic and decreased in-hospital mortality among CMC. This study’s results suggest that the outcomes of public health interventions are not always equal across population groups. Groups of people with greater risk require special attention and monitoring when crafting population-level recommendations. Future evaluations of the effect of nonpharmaceutical interventions during subsequent periods in the pandemic when the infection rate in children was higher (eg, Omicron) and during nonpandemic periods of increased respiratory illness may be warranted.

Accepted for Publication: October 5, 2023.

Published: November 14, 2023. doi:10.1001/jamanetworkopen.2023.43318

Corresponding Author: Eyal Cohen, MD, MSc, The Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada ( [email protected] ).

Author Contributions: Ms Belza had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Belza, Nelson, Aoyama, Buchanan, Guttmann, Moore Hepburn, Mahant, Saunders, Cohen.

Acquisition, analysis, or interpretation of data: Belza, Pullenayegum, Nelson, Aoyama, Fu, Buchanan, Diaz, Goldberg, Moore Hepburn, Mahant, Martens, Nathwani, Saunders, Cohen.

Drafting of the manuscript: Belza, Aoyama.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Belza, Pullenayegum, Nelson, Aoyama, Fu, Nathwani.

Obtained funding: Nelson, Aoyama, Saunders, Cohen.

Administrative, technical, or material support: Nelson, Moore Hepburn, Martens.

Supervision: Pullenayegum, Cohen.

Conflict of Interest Disclosures: Dr Saunders reported grants from Canadian Institute of Health Research unrelated to the current study; and personal fees from The BMJ Group, Archives of Diseases in Childhood outside the submitted work. Dr Cohen reported being a member of the Committee to Evaluate Drugs, which provides advice to Ontario’s Ministry of Health on public drug policy. No other disclosures were reported.

Funding/Support: This study was funded by the Canadian Institute of Health Research (grant No. WI2-179915).

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The opinions, results and conclusions reported in this study are those of the authors and are independent of the funding sources. No endorsement by Canadian Institute for Health Information is intended or should be inferred.

Data Sharing Statement: See Supplement 2 .

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Normal Respiratory Rates and Why They Change

In Children

During Exercise

When to Call a Provider

A normal respiratory rate for adults is between 12 to 18 breaths per minute. Normal respiratory rates for children depend on their age, with babies and toddlers taking more breaths per minute. Typically, a normal respiratory rate for newborns is 30 to 60 breaths per minute.

Your respiratory rate is the number of breaths you take in a one-minute period while at rest. Normal respiratory rates vary slightly by age or exertion level, but they also can change due to a health problem. it's important to know how to measure a respiratory rate correctly.

Illustration by Jessica Olah for Verywell Health

Normal Respiratory Rate in Children

Children breathe more quickly than adults and what's "normal" varies by age. Once they have reached their teen years, children usually breathe at the same rate as adults do.

Infants usually have a much faster breathing rate than older children. They can also have what's called periodic breathing. With periodic breathing, a child's average respiratory rate speeds up and slows down. They may have periods during which they breathe slower than normal followed by a few minutes of breathing much faster than normal.

Periodic breathing can be frightening for a parent. But it's usually normal unless your child has other symptoms of an underlying medical condition.

Respiratory Rate: Normal Range by Age

Newborn	30 to 60
Infant (1 to 12 months)	30 to 60
Toddler (1 to 2 years)	24 to 40
Preschooler (3 to 5 years)	22 to 34
School-aged child (6 to 12 years)	18 to 30
Adolescent (13 to 17 years)	12 to 16

Normal Respiratory Rate In Adults

A respiratory rate should be measured when a person is at rest, not after intense activity. An adult normally will breathe between 12 and 16 times per minute. In general, breathing rates are slightly faster in females than males.

When adults have periodic swings in breathing rates, it can be a sign of a health problem. One type of periodic breathing in adults is called Cheyne-Stokes breathing , a pattern of fast, shallow breaths along with periods of no breathing or slow breathing. This type of erratic breathing is not considered normal and may be caused by:

Congestive heart failure
Carbon monoxide poisoning
Low sodium level in the blood ( hyponatremia )
High altitude
Final stages of dying

Respiratory Rate in Older Adults

Studies suggest that respiratory rates in older adults tend to be higher than those of younger adults. Lung function tends to decrease with age, even in people who do not have an underlying lung disease like chronic obstructive pulmonary disease (COPD).

Exercise makes your muscles work harder, and in order for them to work harder, they need to use more oxygen to make more energy. This means that:

The normal respiratory rate for a healthy adult during exercise can increase to 40 to 60 breaths per minute. The increased breathing rate allows more oxygen to reach your lungs.
Children also breathe faster while exercising, and they may occasionally feel mildly short of breath for a temporary time.

Fast breathing that is accompanied by other symptoms like coughing or wheezing is not normal at any age, however, and should be evaluated by a healthcare professional.

Is 30 breaths a minute normal?

Thirty breaths per minute is a normal respiratory rate for children up to 12 years of age. A rate of 30 breaths per minute in an adolescent or resting adult is considered abnormal and may warn of a health issue.

Types of Abnormal Respiratory Rates

Medical professionals use several terms to describe abnormal rates, including:

Bradypnea is breathing that is abnormally slow.
Tachypnea is an elevated respiratory rate. These fast breaths are usually shallow.
Dyspnea means shortness of breath . It can occur with a high, normal, or low respiratory rate.
Hyperpnea is breathing that is deep and labored. It may occur with or without rapid breathing.
Apnea means literally “no breath." It's a period where breathing stops.

An "abnormal respiratory rate" is a respiratory rate that is too fast or too slow compared to what would be expected for someone your age. For example, having a severe infection leads to more rapid rates. A head injury, stroke, or overdose may cause slower than normal breathing.

Recent studies suggest that knowing your respiratory rate can help your healthcare provider predict serious medical events. Studies also suggest that respiratory rates are not measured as often as they should be. It's been coined the “ignored vital sign.”

Increased Respiratory Rate

In adults, a breathing rate over 20 breaths per minute is usually considered elevated. A rate over 24 breaths per minute suggests a serious condition that may include:

Acidosis : When the acid level in the blood goes up, so does the amount of carbon dioxide. That's why the breathing rate spikes. This can occur with metabolic conditions like diabetes ( diabetic ketoacidosis ). The rapid, deep breathing is referred to as "Kussmaul's respiration."
Asthma : During an asthma attack , breathing rates often go up. Even small increases can be a sign of worse breathing problems. It's important to keep a close eye on breathing rates.
Chronic obstructive pulmonary disease (COPD) : Chronic obstructive pulmonary disease is a common cause of rapid breathing. It's often present in people with a history of smoking.
Dehydration : Dehydration can speed up your breathing.
Fever : When you have a fever, your body tries to cool you off by breathing faster. Rapid breathing may mean an infection is getting worse. It's important to consider fever if you're measuring a breathing rate.
Heart conditions : People with heart failure and other heart conditions often have elevated breathing rates.
Hyperventilation : People may breathe more rapidly when they feel stress, pain, anger, or panic.
Infections : Flu, pneumonia, tuberculosis, and other infections can cause fast breathing.
Lung conditions : Conditions such as lung cancer , pulmonary emboli (blood clots in that travel to the lungs), and other lung diseases often raise the respiratory rate.
Overdoses : An overdose of aspirin or amphetamines may speed up breathing.

In children, the most common causes of an increased breathing rate include fever and dehydration. Very rapid breathing (a respiratory rate greater than 50) with a fever is cause for concern. Bronchiolitis and pneumonia are common causes. Acidosis and asthma can quicken breathing rates in children, too.

Rapid Respiratory Rate in Newborns

In newborns, common causes of a rapid respiratory rate include transient tachypnea of the newborn (TTN)—a mild condition. It can also be caused by more serious problems such as respiratory distress syndrome.

Decreased Respiratory Rate

Some experts define a low respiratory rate as less than 12 breaths a minute in adults. A lower breathing rate is often cause for concern.

Some causes of a lower rate include:

Alcohol : Drinking alcohol can slow your breathing rate.
Brain conditions : Damage to the brain, such as strokes and head injuries, often leads to slower breathing.
Metabolic : Respiratory rate can slow down to balance the effects of abnormal metabolic processes in the body.
Narcotics : Some medications such as narcotics—whether used for medical purposes or illegally—can slow breathing.
Sleep apnea : With sleep apnea , breathing can stop altogether, slow down, or speed up as you sleep.

Make sure to use the rate ranges for children when you're counting a child's breaths and use the adult ranges for adults.

When to Call Your Healthcare Provider

If your breathing rate changes, it's a good reason to contact your healthcare provider. This is especially true if you have a condition such as asthma or heart disease. An increased respiratory rate alone can be a warning sign.

If you're a healthcare professional, pay close attention to this often-ignored vital sign. One study found that measuring respiratory rate around the time of discharge from the emergency room helped to predict problems after discharge.

Your respiratory rate is the number of breaths you take in one minute. Adults typically breathe at a slower rate than children. Your respiratory rate is an important measurement because many health conditions, some of them serious, can change how fast or slow you breathe. When your breathing rate changes, it may mean your body isn't getting enough oxygen.

Fever, dehydration, and infection can all speed up your breathing. So can long-term health conditions like asthma, COPD, and heart problems. Alcohol, medications, sleep apnea, brain injuries, and metabolic issues can all slow your breathing.

If you notice changes to your respiratory rate, talk to a healthcare professional. You may be dealing with a health condition that needs treatment.

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Della Torre V, Badenes R, Corradi F, et al. Acute respiratory distress syndrome in traumatic brain injury: how do we manage it? J Thorac Dis . 2017;9(12):5368-5381. doi:10.21037/jtd.2017.11.03

Garrido D, Assioun JJ, Keshishyan A, Sanchez-Gonzalez MA, Goubran B. Respiratory rate variability as a prognostic factor in hospitalized patients transferred to the intensive care unit . Cureus . 2018;10(1):e2100. doi:10.7759/cureus.2100

Nicolò A, Massaroni C, Schena E, Sacchetti M. The importance of respiratory rate monitoring: From healthcare to sport and exercise. Sensors (Basel) . 2020;20(21):6396. doi:10.3390/s20216396x

Arnold DH, Penrod CH, Sprague DJ, Hartert TV. Count on it! Accurately measured respiratory rate is associated with lung function and clinical severity in children with acute asthma exacerbations. J Pediatr. 2016;175:236-236.e1. doi: 10.1016/j.jpeds.2016.04.081

Baumert M, Linz D, Stone K, et al. Mean nocturnal respiratory rate predicts cardiovascular and all-cause mortality in community-dwelling older men and women. Eur Respir J . 2019;54(1):1802175. doi:10.1183/13993003.02175-2018

Goetze S, Zhang Y, An Q, et al. Ambulatory respiratory rate trends identify patients at higher risk of worsening heart failure in implantable cardioverter defibrillator and biventricular device recipients: a novel ambulatory parameter to optimize heart failure management. J Interv Card Electrophysiol . 2015;43(1):21-29. doi:10.1007/s10840-015-9983-6

Hennelly KE, Ellison AM, Neuman MI, Kline JA. Clinical variables that increase the probability of pulmonary embolism diagnosis in symptomatic children. Res Pract Thromb Haemost . 2019;4(1):124-130. doi:10.1002/rth2.12265

Lancaster General Health. When to Call the Doctor about Your Child’s Fever .

El-Fattah NMA, El-Mahdy HS, Hamisa MF, Ibrahim AM. Thoracic fluid content (TFC) using electrical cardiometry versus lung ultrasound in the diagnosis of transient tachypnea of newborn . Eur J Pediatr . 2024 Jun;183(6):2597-2603. doi: 10.1007/s00431-024-05507-5

Fox LM, Hoffman RS, Vlahov D, Manini AF. Risk factors for severe respiratory depression from prescription opioid overdose . Addiction . 2018 Jan;113(1):59-66. doi:10.1111/add.13925

Larson M, Chantigian DP, Asirvatham-Jeyaraj N, Van de Winckel A, Keller-Ross ML. Slow-paced breathing and autonomic function in people post-stroke . Front Physiol . 2020;11:573325. doi:10.3389/fphys.2020.573325

UpToDate. Respiratory function in thyroid disease .

Jung H, Kim D, Choi J, Joo EY. Validating a Consumer Smartwatch for Nocturnal Respiratory Rate Measurements in Sleep Monitoring . Sensors (Basel) . 2023 Sep 19;23(18):7976. doi:10.3390/s23187976

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Li T, Divatia S, McKittick J, et al. A pilot study of respiratory rate derived from a wearable biosensor compared with capnography in emergency department patients . Open Access Emerg Med. 2019. 11:103-108. doi:10.2147/OAEM.S198842

By Lynne Eldridge, MD Lynne Eldrige, MD, is a lung cancer physician, patient advocate, and award-winning author of "Avoiding Cancer One Day at a Time."

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Ital J Pediatr

Maternal and neonatal risk factors for neonatal respiratory distress syndrome in term neonates in Cyprus: a prospective case–control study

Paraskevi stylianou-riga.

1 Neonatal Intensive Care Unit, “Archbishop Makarios III” Hospital, Nicosia, Cyprus

2 Respiratory Physiology Laboratory, Medical School, University of Cyprus, 2029 Aglantzia, Nicosia, Cyprus

3 Neonatal Department, Aretaieio Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

Theodora Boutsikou

Panayiotis kouis, paraskevi kinni, marina krokou, andriani ioannou, tania siahanidou.

4 Neonatal Unit, First Department of Pediatrics, ‘Aghia Sophia’ Children’s Hospital, Athens, Greece

Zoi Iliodromiti

Thalia papadouri, panayiotis k. yiallouros, nicoletta iacovidou, associated data.

The datasets generated and/or analyzed during the current study are not publicly available due to the requirements of Ethics approval but are available from the corresponding author on reasonable request.

Neonatal respiratory distress syndrome (NRDS) is strongly associated with premature birth, but it can also affect term neonates. Unlike the extent of research in preterm neonates, risk factors associated with incidence and severity of NRDS in term neonates are not well studied. In this study, we examined the association of maternal and neonatal risk factors with the incidence and severity of NRDS in term neonates admitted to Neonatal Intensive Care Unit (NICU) in Cyprus.

In a prospective, case-control design we recruited term neonates with NRDS and non-NRDS admitted to the NICU of Archbishop Makarios III hospital, the only neonatal tertiary centre in Cyprus, between April 2017–October 2018. Clinical data were obtained from patients’ files. We used univariate and multivariate logistic and linear regression models to analyse binary and continuous outcomes respectively.

During the 18-month study period, 134 term neonates admitted to NICU were recruited, 55 (41%) with NRDS diagnosis and 79 with non-NRDS as controls. In multivariate adjusted analysis, male gender ( OR : 4.35, 95% CI: 1.03–18.39, p = 0.045) and elective caesarean section ( OR : 11.92, 95% CI: 1.80–78.95, p = 0.01) were identified as independent predictors of NRDS. Among neonates with NRDS, early-onset infection tended to be associated with increased administration of surfactant ( β :0.75, 95% CI: − 0.02-1.52, p = 0.055). Incidence of pulmonary hypertension or systemic hypotension were associated with longer duration of parenteral nutrition (pulmonary hypertension: 11Vs 5 days, p < 0.001, systemic hypotension: 7 Vs 4 days, p = 0.01) and higher rate of blood transfusion (pulmonary hypertension: 100% Vs 67%, p = 0.045, systemic hypotension: 85% Vs 55%, p = 0.013).

Conclusions

This study highlights the role of elective caesarean section and male gender as independent risk factors for NRDS in term neonates. Certain therapeutic interventions are associated with complications during the course of disease. These findings can inform the development of evidence-based recommendations for improved perinatal care.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13052-021-01086-5.

Neonatal Respiratory Distress Syndrome (NRDS) is the main cause of neonatal respiratory failure and death [ 1 ], as well as admission in Neonatal Intensive Care Unit (NICU) [ 2 ]. NRDS is more frequent in preterm neonates [ 3 ], but it can affect term neonates as well. Nevertheless, the underlying aetiologies of NRDS in term neonates are different to those of NRDS in preterm neonates [ 4 ], so that NRDS in term neonates is frequently perceived as a distinct pathology [ 5 ].

Even in term neonates the frequency of NRDS has been linked to gestational age [ 6 ] and caesarean section [ 7 ], especially when performed before 39 weeks of gestation [ 8 – 11 ]. Other risk factors that have been associated with NRDS in term neonates include neonatal asphyxia, maternal or fetal infection, premature rupture of membranes and male gender [ 12 ]. However, most publications on the association of risk factors with NRDS relied on retrospective or administrative data [ 13 – 18 ] or did not focus on NRDS severity, management and resolution [ 19 – 22 ]. The few studies that assessed the association of maternal or neonatal risk factors with incidence but also the outcomes and severity of NRDS in term neonates were limited by studying a mixed population of both preterm and term neonates [ 23 – 25 ] or by retrospective data collection [ 26 ].

In Cyprus, a country of 875,000 inhabitants, known for the very high frequency of caesarean section deliveries (52.2% of all deliveries in 2018) [ 27 ], the annual incidence of NRDS in term and pre-term neonates is currently unknown. Furthermore, the frequency of other risk factors for NRDS and their association with incidence and severity of NRDS has never been studied in this setting.

The aim of this study was to investigate prospectively the frequency of NRDS in term neonates in Cyprus and examine the association between prenatal, perinatal and postnatal factors with incidence and severity of NRDS among this population. We also aimed to examine the association of several therapeutic interventions with severity and complications of NRDS.

Study location

The study was performed at the grade III-IV NICU (48 infant beds capacity) of Archbishop Makarios III (NAM III) hospital which serves the whole of Cyprus as the single national tertiary referral centre for all high-risk pregnancies and neonates requiring intensive care support.

Study population and case-control selection

We obtained the total number of births in Cyprus for 2017 and 2018 from the Health Monitoring Unit of the Ministry of Health and the National Statistics Department, and the total number of neonates hospitalised in the NICU for the same period from the Unit’s records. Term neonates (gestational age ≥ 37 weeks) that were hospitalised in the NICU between April 2017 and October 2018 were prospectively recruited. Term neonates were defined as NRDS cases if they required mechanical ventilation and surfactant administration and fulfilled at least two of the following criteria: (a) tachypnea, (b) central cyanosis in room air, (c) expiratory grunting, (d) intercostals or jugular retractions and nasal flaring and (e) oxygen supplementation requirement during the first 2 days of life [ 5 , 28 ]. Term neonates without NRDS that received standard neonatal nursing care were defined as controls. Neonates with known chromosomal abnormalities and congenital anatomical anomalies were excluded from the study.

Ethics approval

All guardians of participating neonates provided written informed consent and the study was approved by the Cyprus National Bioethics Committee (EEBK EΠ 2017.01.22) and the Research Committee of the Cyprus Ministry of Health (Protocol approval: 0416/2017).

Data collection

Maternal, anthropometric and medical data, were collected from the mothers’ medical notes. Maternal clinical data included pre-existing chronic conditions such as diabetes mellitus, thyroid gland disorders and heart disease as well as data on pregnancy complications, gestational diabetes, hypertensive disorders of pregnancy (eclampsia, preeclampsia), placental abnormalities, infections and mode of delivery. Mortality and neonatal clinical data were collected until discharge from the NICU. Neonatal clinical data included gestational age, respiratory distress diagnosis, requirement for neonatal resuscitation at the delivery room, meconium stained amniotic fluid, Apgar score, pH and base excess on admission, hypotension during the first 24 h of life, nutrition status, treatment received, NICU duration of hospitalization and respective complications. For neonates with NRDS, several other clinical parameters were also collected such as duration of mechanical ventilation, number of surfactant-replacement doses, NRDS complications (pneumothorax, pulmonary hypertension, hemodynamic instability), neonatal infection, antibiotic administration and nutrition management. Additionally, results of laboratory measurements (e.g. blood gases and blood glucose, lactic acid and creatinine levels) and brain and heart ultrasound findings were also collected.

Statistical analysis

Continuous variables are presented as means and 95% confidence intervals (95% CI) or medians and interquartile range (IQR), while categorical variables are presented as counts and percentages. Two-way comparisons between continuous variables were carried out using t-test and Mann-Whitney test for normally and non-normally distributed variables, respectively. Categorical variables were compared with chi-square test. Univariate and multivariate logistic regression analysis was carried out to assess the association of different variables with NRDS and crude and adjusted Odds Ratios (OR) were reported with 95% CI. Parameters that yielded significant associationsin the univariate analysis were included in the multivariate analysis. For the assessment of the effect of clinical parameters on NRDS severity, univariate and multivariate linear regression analyses were carried out. In addition, separate analyses were performed for three different measures of NRDS severity: (a) duration of NICU hospitalisation (b) duration of mechanical ventilation and (c) number of surfactant doses administered. All statistical analyses were performed using STATA 12 (StataCorp, TX). P value < 0.05 was set as the cut-off for statistical significance.

During years 2017 and 2018, there were 9229 and 9329 live births in Cyprus, respectively. In 2017, 662 neonates (245 term) were admitted to the tertiary referral NICU of Cyprus and in 2018, 661 (243 term). Among the term neonates admitted to the NICU, 22.0% were diagnosed with NRDS in 2017 and 23.5% in 2018. During the 18-month study period (April 2017–October 2018), a total of 134 term neonates were recruited, 55 with NRDS diagnosis and 79 non-NRDS neonates as controls (Table 1 ). The primary reasons for NICU admission for non-NRDS neonates were: jaundice requiring only phototherapy treatment (21,5%), low birth weight (5%), mild feeding difficulties (11.4%), transient tachypnea (39.3%), suspicion of early neonatal infection with negative subsequent blood culture (12.7%), mild perinatal stress (7.6%) and prolonged rupture of membranes (2.5%).

Demographic, clinical and treatment characteristics of mothers and neonates

	NRDS ( = 55)	No NRDS ( = 79)

Female (%)	14/55 (25.5)	37/78 (47.4)	0.01
Smoking during pregnancy (%)	1/48 (2.01)	5/75 (6.7)	0.250
Gestational diabetes (%)	7/47 (14.9)	11/74 (14.9)	0.997
Thrombophilia (%)	1/48 (2.1)	3/75 (4.0)	0.559
Caesarean section (%)	32/55 (58.2)	39/79 (49.4)	0.315
Elective Caesarean (%)	29/32 (90.1)	21/39 (53.9)	0.001
IUGR (%)	1/51 (2.0)	7/74 (9.5)	0.092
Chorio-amnionitis (%)	0/45 (0.0)	1/74 (1.4)	0.434
Oligo-hydramnios (%)	2/45 (4.4)	1/77 (1.3)	0.279
Preeclampsia (%)	1/50 (2.0)	3/76 (4.0)	0.542
Prenatal steroids (%)	5/49 (10.2)	9/76 (11.8)	0.777
Fetal distress (%)	16/49 (32.7)	13/67 (19.4)	0.104
Frequent OB visits (%)	46/53(86.8)	75/79(95.0)	0.097
Blood transfusion (any) (%)	40/55 (72.7)	15/79 (18.9%)	< 0.001
Resuscitation at birth (%)	24/52 (46.2)	14/63 (22.2)	0.007
Plasma transfusion (%)	38/55 (69.1)	12/79 (15.2%)	< 0.001
RBC transfusion (%)	14/55 (25.4)	4/79 (5.1%)	0.001
Platelets transfusion (%)	2/55 (3.6)	1/79 (1.3%)	0.362
Dopamine administration (%)	33/55 (60.0)	3/79 (3.8%)	< 0.001
Dobutamine administration (%)	17/55 (30.9)	1/79 (1.3%)	< 0.001

Gestational Age (weeks)	38.3 (37.96, 38.62)	38.6 (38.3–38.8)	0.100*
Birthweight (gr)	3146 (3035, 3256)	3160 (3044–3276)	0.866
Maternal Age (years)	31.1 (29.9, 32.3)	30.8 (29.6–31.9)	0.696
Maternal BMI (kg/m )	23.8 (22.1, 25.4)	23.7 (22.4–25.1)	0.970*
pH	7.31 (7.28,7.34)	7.40 (7.37–7.42)	< 0.001
Base Excess	−6.72 (−7.78, −5.66)	−4.92 (− 5.58, − 4.26)	0.004
Parenteral nutrition (days)	8.24 (3.96, 12.52)	1.51 (1.02, 1.99)	< 0.001
Intravenous Antibiotics (days)	6.98 (6.38, 7.58)	5.86 (4.58, 7.15)	0.115
Apgar at 5 min	8.92 (8.6–9.3)	9.46 (9.2–9.7)	0.002*

IUGR Intrauterine Growth Restriction, OB Obstetrician, RBC Red blood cells, BMI Body mass Index

*Mann Whitney U Test for comparison of medians

NRDS and non-NRDS neonates had similar gestational age (38.3 weeks Vs 38.6 weeks, p value : 0.100), birthweight (3145.9 g Vs 3160 g, p value : 0.866) and maternal risk factors such as gestational diabetes (14.9% Vs 14.9%, p value : 0.997), preeclampsia (2% Vs 4%, p value : 0.542) and thrombophilia (2.1% Vs 4.0%, p value :0.559). However, in comparison to the non-NRDS controls, NRDS term neonates were more frequently males (74.5% Vs 53.6%, p value : 0.01), had a lower mean Apgar Score at 5 min (8.92 Vs 9.46, p value : 0.002) and were more frequently born by elective caesarean section (90.1% Vs 53.9%, p value :0.001). In addition, compared to non-NRDS controls, NRDS term neonates required neonatal resuscitation more frequently (46.2% Vs 22.2%, p value : 0.007), were characterised by lower pH (7.31 Vs 7.40, p value < 0.001) and lower base excess (− 6.72 Vs − 4.92 p value : 0.004), Lastly, duration of parenteral nutrition was higher among NRDS compared to non-NRDS neonates (8.24 days Vs 1.51, p value < 0.001), while there was a tendency for longer duration of intravenous antibiotics administration although the difference was not statistically significant (6.98 days Vs 5.86 days, p value : 0.115).

In univariate analysis, incidence of NRDS was significantly associated with male gender (OR: 2.64, 95% CI: 1.24–5.61, p value : 0.011), elective caesarean section (OR: 8.29, 95% CI: 2.16–31.81, p value : 0.002) and Apgar score at 5 min (OR: 0.64, 95% CI: 0.44–0.92, p value : 0.016). The significant association between male gender and elective caesarean section persisted after adjustment for other confounders in multivariate analysis. The adjusted OR for male gender was 4.35 (95% CI: 1.03–18.39, p value : 0.045) and the adjusted OR forelective caesarean section was 11.92 (95% CI: 1.80–78.95, p value : 0.010). The results of the univariate and multivariate analysis are presented in detail in Tables 2 and and3 3 respectively.

Associations between risk factors and incidence of NRDS (univariate analysis)

	OR	95% CI

Male gender	2.64	1.24–5.61	0.011
Smoking	0.29	0.03–2.63	0.276
Gestational diabetes	1.00	0.36–2.80	0.997
Thrombophilia	0.51	0.051–5.05	0.566
Caesarean section	1.42	0.71–2.86	0.315
Elective Caesarean section	8.29	2.16–31.81	0.002
IUGR	0.19	0.02–1.60	0.128
Oligo-hydramnios	3.53	0.31–40.13	0.308
Preeclampsia	0.49	0.50–4.91	0.549
Prenatal steroids	0.85	0.27–2.69	0.777
Fetal distress	2.01	0.86–4.71	0.107
Frequent Obstetrician visits	0.35	0.09–1.26	0.109

Gestational Age (weeks)	0.82	0.59–1.11	0.200
Birthweight (gr)	0.99	0.99–1.00	0.864
Maternal Age (years)	1.01	0.94–1.09	0.693
Maternal BMI	1.00	0.94–1.07	0.970
Apgar at 5 min	0.64	0.44–0.92	0.016
Lactate Acid (mmol/L)	1.03	0.90–1.18	0.633

IUGR Intrauterine Growth Restriction, BMI Body Mass Index

Associations between risk factors and incidence of NRDS (multivariate analysis)

	OR	95% CI

Male gender	4.35	1.03–18.39	0.045
Smoking	8.65	0.31–240.15	0.203
Elective Caesarean section	11.92	1.80–78.95	0.010
IUGR	0.14	0.007–2.41	0.175
Fetal distress	0.32	0.04–2.11	0.239
Frequent Obstetrician visits	1.13	0.15–8.84	0.905

Gestational age (weeks)	1.52	0.65–3.53	0.330
Apgar score at 5 min	0.65	0.29–1.44	0.286

IUGR Intrauterine Growth Restriction

The relationship between clinical parameters and severity of NRDS was evaluated using three different outcome measures (duration of NICU stay, duration of mechanical ventilation and number of surfactant doses administered). Duration ofNICU stay was found to be associated with late-onset infection ( β : 5.91, 95% CI: 1.14–10.66, p value : 0.01) in the univariate analysis, but statistical significance was attenuated after adjustment for other factors, although the effect estimate and its direction were similar ( β : 5.43, 95% CI: 1.40–12.27, p value : 0.114) (Table 4 ). In contrast, duration of mechanical ventilation was not affected by early-onset ( β : 0.58, 95% CI: − 1.42-2.58, p value : 0.557) or late-onset ( β : 0.06, 95% CI: − 2.54-2.67, p value : 0.960) infection (Table 5 ). When number of administered surfactant doses were examined as a measure of NRDS severity, a significant association with early-onset infection ( β :0.98, 95% CI:0.50–1.46, p value < 0.001) and pulmonary hypertension ( β: 1.14, 95% CI:0.52–1.77, p value :0.001) were identified in the univariate analysis. In multivariate analysis, the association with early-onset infection demonstrated a similar magnitude of effect but was marginally non-significant ( β: 0.75, 95% CI: − 0.02-1.52, p value :0.055), while the effect of pulmonary hypertension was markedly attenuated ( β: 0.47, 95% CI: − 0.63-1.56, p value :0.388) (Table 6 ).

Associations between clinical variables and duration of NICU stay

	Univariate analysis			Multivariate analysis
		95% CI			95% CI
Stained Amniotic Fluid	−1.92	−6.13 - 2.27	0.36	−2.37	−7.86 - 3.13	0.384
Early-onset infection	1.18	−2.25 - 4.63	0.4	1.18	−4.07 - 6.43	0.647
Delivery at tertiary center	−1.78	−5.43 - 1.85	0.32	−3.74	−9.72 - 2.10	0.199
Hypotension (first 24 h)	−1.38	−4.89 - 2.12	0.43	−3.43	−8.72 - 1.86	0.194
Hemoglobin	−0.02	−0.74 - 0.69	0.94	−0.36	−1.45 - 0.744	0.512
Fever	1.38	−7.33 - 10.10	0.751	5.96	−8.09 - 20.01	0.391
Hypothermia	0.31	−5.82 - 6.44	0.919	−0.06	− 8.48 - 8.35	0.988
Late-onset infection	5.91	1.14–10.66	0.01	5.43	−1.40 - 12.27	0.114
Pulmonary Hypertension	−0.09	−4.49 - 4.30	0.965	1.45	−6.41 - 9.31	0.708

Associations between clinical variables and duration of mechanical ventilation

	Univariate analysis			Multivariate analysis
		95% CI			95% CI
Stained Amniotic Fluid	14.39	2.68–26.09	0.017	1.32	−0.77 - 3.42	0.206
Early-onset infection	2.30	0.72–3.89	0.005	0.58	−1.42 - 2.58	0.557
Delivery at tertiary center	−2.64	−13.36 - 8.08	0.623	0.25	−1.98 - 2.48	0.820
Hypotension (first 24 h)	5.31	−4.66 - 15.27	0.290	0.68	−1.34 - 2.69	0.497
Hemoglobin	−0.28	−0.63 - 0.07	0.118	0.06	−0.36 - 0.48	0.773
Fever	−0.72	−5.07 - 3.62	0.739	1.64	−3.73 - 6.99	0.536
Hypothermia	−1.1	−18.93 - 16.73	0.902	−0.12	−3.34 - 3.09	0.938
Late-onset infection	−2.31	−18.63 - 14.02	0.777	0.06	−2.54 - 2.67	0.960
Pulmonary Hypertension	17.63	6.57–28.69	0.002	2.82	−6.65 - 9.15	0.747

Associations between clinical variables and surfactant doses

	Univariate analysis			Multivariate analysis
		95% CI			95% CI
Stained Amniotic Fluid	0.061	−0.64 - 0.76	0.863	−0.23	−0.99 - 0.54	0.547
Early-onset infection	0.98	0.50–1.46	0.000	0.75	−0.02 - 1.52	0.055
Delivery at tertiary center	0.19	−0.42 - 0.81	0.529	0.19	−0.66 - 1.05	0.649
Hypotension (first 24 h)	0.52	−0.04 - 1.07	0.067	0.19	−0.54 - 0.93	0.595
Hemoglobin	−0.072	−0.19 - 0.04	0.212	0.07	−0.09 - 0.23	0.392
Fever	−0.04	−1.43 - 1.35	0.952	0.68	−1.27 - 2.63	0.477
Hypothermia	0.204	−0.80 - 1.21	0.686	0.05	−0.96 - 1.04	0.932
Late-onset infection	−0.06	−0.89 - 0.78	0.890	−0.36	−1.31 - 0.59	0.443
Pulmonary Hypertension	1.14	0.52–1.77	0.001	0.47	−0.63 - 1.56	0.388

NRDS complicated with pulmonary hypertension was associated with significantly higher duration of parenteral nutrition (11 Vs 5 days, p value < 0.001) and more frequent need for blood transfusion (100% Vs 67%, p value : 0.045) when compared to NRDS without pulmonary hypertension. Similarly, in NRDS neonates, those with hypotension required parenteral nutrition for a significantly higher number of days (7 Vs 4 days, p value :0.010) and received blood transfusion more frequently (84.9% Vs 54.6%, p value :0.013) compared to those without hypotension. Between NRDS neonates with and without late-onset infection, no significant difference in the distribution of treatment modalities was observed (Supplementary Table 1 ).

In this prospective, case-control study, we report the incidence and clinical characteristics of NRDS in term neonates in Cyprus and evaluate the association of prenatal, perinatal and postnatal risk factors with the appearance and severity of this condition. The annual incidence of NRDS, among term neonates admitted to the NICU in Cyprus, ranged from 22.0% in 2017 to 23.5% in 2018 and it was more frequent among males and neonates born with an elective caesarean section. Early-onset infection was marginally associated with increased administration of surfactant, while hypotension and pulmonary hypertension were associated with longer duration of parenteral nutrition and higher rate of blood transfusions.

A positive association between male gender and NRDS was reported by Zhao D et al. [ 29 ]. The protective effect of female gender can be explained by the augmenting effect of estrogens on alveolar development and surfactant production [ 30 ]. The important role of estradiol and progesterone for fetal lung development has been reported to be mediated by an increase in vascular endothelial growth factor (VEGF) [ 31 ], which stimulates the proliferation and maturation of alveolar type II cells [ 32 ]. In animal studies, chronic androgen exposure in utero was found to delay surfactant production in male embryos [ 33 ], possibly through the epidermal growth factor (EGF-R) and transforming growth factor-beta (TGFβ-R) signaling pathways [ 34 ].

Previous studies have demonstrated that elective caesarean section, in the absence of labor signs, is associated with increased risk for NRDS [ 4 , 20 , 35 ]. Onset of spontaneous labor has been shown to lead to rapid clearance of fetal lung fluids and lung maturation [ 10 ], while higher gestational age is predictive of a favorable respiratory prognosis even in term neonates undergoing elective caesarean section [ 36 – 38 ].

Very few studies have examined the association of clinical parameters with severity indices or outcomes in NRDS and most of them were limited by small sample size and inconsistencies in the examined risk factors [ 12 , 39 , 40 ]. In our study, we found late-onset and early-onset infection to be associated with duration of NICU stay and duration of mechanical ventilation respectively in univariate analysis. It is known that mechanical ventilation is an independent risk factor for development of neonatal infection [ 41 , 42 ]. However, it is possible that development of septic shock as a result of early or late-onset infection may require or prolong the need for mechanical ventilation [ 43 , 44 ]. Univariate analysis also demonstrated that pulmonary hypertension was associated with both longer duration of mechanical ventilation and increased number of surfactant doses. Although this finding was attenuated in multivariate analysis, it is in line with previous reports. More specifically, the mainstay for pulmonary hypertension management includes optimal lung expansion and adequate oxygenation [ 45 – 47 ], while exogenous surfactant administration has been shown to significantly improve outcomes of pulmonary hypertension secondary to NRDS [ 45 , 48 ]. In our ventilated neonates, we implemented modern modes of mechanical ventilation with synchronized intermittent positive pressure ventilation (SIPPV), which has been shown to be associated with a shorter overall duration of ventilation in term neonates as compared to intermittent mandatory ventilation [ 49 ]. Nevertheless, more sophisticated methods of mechanical ventilation such as volume targeted ventilation are increasingly being used and have been shown to further improve clinical outcomes by allowing finer control of ventilated tidal volume [ 50 , 51 ]. Well controlled ventilation avoids the risk of volutrauma due to high tidal volume, reduces hypocarbia and risk of brain injury in case of frequent tidal volume fluctuations and avoids very low expired tidal volume that has been associated with atelectotrauma and hypercarbia [ 52 ]. Future use of volume targeted ventilation in our NICU, is expected to further improve patient outcomes.

This study demonstrated that NRDS neonates with early-onset infection required increased surfactant administration as compared to NRDS neonates without early-onset infection. An increased requirement for surfactant therapy for early onset pneumonia has been previously reported in late preterm and term neonates [ 53 ], while a slower response to surfactant therapy was found in specific types of infection such as group B streptococcal pneumonia [ 54 ]. The most likely mechanism explaining the requirement of additional exogenous surfactant in early onset infection is the impairment of endogenous surfactant synthesis or secretion of proteinases and other microbial components that degrade or inhibit surfactant-associated proteins. These components have been found to be excreted by a number of different respiratory pathogens such as P. aeruginosa [ 55 ], adenovirus and respiratory syncytial virus [ 56 , 57 ] and Aspergillus fumigatus [ 58 ]. Nevertheless, to date, the overall effect of surfactant therapy on mortality and pulmonary complications in infants with bacterial pneumonia is not clear and further research is required [ 59 ].

Pulmonary hypertension as well as systemic hypotension in NRDS term neonates were also strongly associated with duration of parenteral nutrition. Neonates in mechanical ventilation often have increased nutritional requirements and meeting these requirementsis a challenging task [ 60 ]. Parenteral nutrition is a necessary life sustaining practice [ 61 ] and according to the European Consensus Guidelines on the Management of Respiratory Distress Syndrome, administration of parenteral nutrition should be initiated as soon as possible to reduce growth delay in neonates [ 62 ]. Nevertheless, other authors suggest that parenteral nutrition should only be initiated after clinical stabilization of the neonate [ 63 ]. In our study, blood transfusion was more frequent in NRDS neonates compared to non-NRDS neonates, especially when NRDS was further complicated by pulmonary hypertension and systemic hypotension. Red blood cells transfusion is often required to prevent the effects of anemia among NRDS neonates [ 64 ] but administration should always adhere to standing guidelines due to the increased risk of complications [ 65 ].

The major strengths of this study include the prospective recruitment of participants as well as the prospective data collection which was characterised by high data completeness. Furthermore, the study benefits from a well-defined study population as twins and neonates with congenital abnormalities were excluded a priori. Lastly, given that NAM III hospital NICU serves as the only tertiary referral centre in Cyprus, the study population was not restricted by maternal socioeconomic status and thus results are not affected by selection bias and can be generalised across the socioeconomic spectrum. However, this work is also characterised by some limitations. For ethical reasons, neonates (with or without NRDS) that died during NICU hospitalisation, were not included in the study and thus the study is limited to only morbidity outcomes. Nevertheless, during the study period, mortality in the NICU among term neonates was very low (1/245 in 2017 and 0/243 in 2018). Furthermore, we assessed only short-term clinical severity outcomes and did not address the association of maternal and neonatal risk factors with long-term complications. Lastly, our dataset did not include information on neonatal morbidity scoring systems such as the Clinical Risk Index for Babies (CRIB) [ 66 ] that has been previously suggested to predict NRDS severity [ 67 ] in neonates.

Male gender and elective cesarean section are significant risk factors for NRDS among term neonates admitted to NICU. NRDS complicated with early-onset infection requires higher surfactant dose while hypotension and pulmonary hypertension are associated with higher duration of parenteral nutrition and higher rate of blood transfusion. To our knowledge, this is the first study to examine term NRDS population in Cyprus. In this respect, our results highlight the importance of specific risk factors in the development and severity of NRDS in term neonates and can be used to inform evidence-based NRDS management protocols in the NICU, develop strategic planning for obstetric management and hopefully set the basis for further epidemiological studies.

Acknowledgments

The authors are grateful to the study participants for their participation and to the nursing staff of “Archbishop Makarios III” hospital for their cooperation.

Abbreviations

NRDS	Neonatal Respiratory Distress Syndrome
NICU	Neonatal Intensive Care Unit
OR	Odds Ratio
CI	Confidence interval
IQR	Interquartile range
VEGF	Vascular endothelial growth factor
EGF-R	epidermal growth factor
TGFβ-R	Transforming growth factor-beta
SIPPV	Synchronized intermittent positive pressure ventilation
CRIB	Clinical Risk Index for Babies
SNAP	Score for Neonatal Acute Physiology

Authors’ contributions

PSR, NI, PKY and TB contributed substantially to the study hypothesis and study design. PSR, PK, MK, AI and TP participated in data collection and prepared the study dataset. TS and ZI participated in data cleaning and data quality control. PSR and PK performed the statistical analysis and PSR, PK, TB prepared the first draft of the manuscript. NI, PKY contributed towards interpretation of findings and all authors have read, revised and approved the final version of the manuscript.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Availability of data and materials

Declarations.

Not applicable

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Paraskevi Stylianou-Riga and Theodora Boutsikou are contributed equally as co-first authors.

Contributor Information

Paraskevi Stylianou-Riga, Email: [email protected] .

Theodora Boutsikou, Email: moc.liamg@kstboeht .

Panayiotis Kouis, Email: [email protected] .

Paraskevi Kinni, Email: [email protected] .

Marina Krokou, Email: [email protected] .

Andriani Ioannou, Email: [email protected] .

Tania Siahanidou, Email: rg.aou.dem@nahais .

Zoi Iliodromiti, Email: rg.oohay@itimordoiliz .

Thalia Papadouri, Email: [email protected] .

Panayiotis K. Yiallouros, Email: [email protected] .

Nicoletta Iacovidou, Email: moc.liamg@85caicin .

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Neonatal Respiratory Distress Syndrome: Tackling A Worldwide Problem
About 12% of babies born in the U.S. are born prematurely-a higher rate than in other developed countries. Preterm birth is the world's number-one cause of newborn deaths (almost 30%). Neonatal respiratory distress syndrome is the leading cause of death in premature infants. The risk of RDS depends on gestational age: > 50% at < 28 weeks ...
Persistent respiratory distress in a neonate: a ...
We present a 17-day-old term, female baby who was referred to our centre for persistent respiratory distress. She was managed for pneumonia and pneumothorax at the primary care centre. On detailed clinical examination at admission, a possibility of congenital lobar emphysema (CLE) was considered. A CT chest was performed, and diagnosis of CLE was confirmed. The infant was managed with ...
Case 2: Recurrent Respiratory Distress in a Newborn
A 2-day-old boy born without complication at 38 weeks' gestation to a healthy mother via spontaneous vaginal delivery presented to the emergency department with 2 episodes of apnea and cyanosis after discharge from the newborn nursery. One episode had occurred during breastfeeding, and the other hours after feeding. Of note, his mother reported that a similar cyanotic event had occurred ...
Maternal and neonatal risk factors for neonatal respiratory distress
Maternal and neonatal risk factors for neonatal respiratory ...
A nationwide survey on the management of neonatal respiratory distress
Background: At present, preterm infants with respiratory distress syndrome (RDS) in China present higher mortality and morbidity rates than those in high-income countries. The aim of this nationwide survey was to assess the clinical management of RDS in China. Methods: A nationwide cross-sectional survey to assess adherence to RDS management recommendations was performed.
A nationwide survey on the management of neonatal respiratory distress
Neonatal respiratory distress syndrome (RDS) is a prevalent pulmonary condition observed in preterm infants, and is primarily linked to insufficient pulmonary surfactant (PS) or underdeveloped lung structures [1, 2].RDS affects approximately 30% of infants born between 28 and 34 weeks of gestation, with the prevalence increasing to approximately 60% for those born before 28 weeks [].
Epidural analgesia in labour and neonatal respiratory distress: a case
Results: In our study, 206 cases and 206 matched controls were enrolled. Exposure to epidural analgesia was present in 146 (70.9%) cases as compared with 131 (63.6%) of the controls. The association between exposure to epidural analgesia and respiratory distress in neonates was statistically significant upon adjustment for all potential ...
Respiratory Distress in the Newborn
Respiratory Distress in the Newborn - PMC
CASE PRESENTATION ON. Respiratory Distresss
The document presents a case of respiratory distress syndrome (RDS) in a 3-day-old male infant. Key details include: 1. The infant presented with difficulty breathing, fast breathing rate, and was born prematurely at low birth weight. 2. Physical examination found signs of respiratory distress including a fast heart rate and blue skin discoloration. 3. The infant was diagnosed with RDS, likely ...
Predicting Mortality in Sepsis-Associated Acute Respiratory Distress
This retrospective cohort study included 2466 patients diagnosed with sepsis and ARDS within 24 h of ICU admission. Demographic, clinical, and laboratory parameters were extracted from Medical Information Mart for Intensive Care III (MIMIC-III) database.
Severe Respiratory Disease Among Children With and Without Medical
Key Points. Question Did rates and outcomes of severe respiratory illness change during the first 2 years of the pandemic, compared with prepandemic, among children with medical complexity and those without medical complexity?. Findings In this repeated cross-sectional study of 139 078 respiratory hospitalizations in Canada, there were more than 45 000 fewer respiratory hospitalizations, more ...
Case 1: A newborn in distress
Case 1: A newborn in distress - PMC
Normal Respiratory Rates and Why They Change
Normal Respiratory Rate by Age
Maternal and neonatal risk factors for neonatal respiratory distress
Neonatal Respiratory Distress Syndrome (NRDS) is the main cause of neonatal respiratory failure and death , as well as admission in Neonatal Intensive Care Unit (NICU) . NRDS is more frequent in preterm neonates , but it can affect term neonates as well. ... In this prospective, case-control study, we report the incidence and clinical ...
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TABLE OF CONTENTS. ABBREVIATIONS ...

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A nationwide survey on the management of neonatal respiratory distress syndrome: insights from the MUNICH survey in 394 Chinese hospitals

MUNICH Study Group

Conclusions

Study design and participants

Questionnaire preparation

Questionnaire distribution and data collection

Statistical analyses

Profiles of the included physicians and hospitals

Bed capacity and human resources

Main points of RDS care

Delivery rooms

Oxygen therapy in DRs

T-piece resuscitators

PS administration in DRs

PS administration

Caffeine therapy

Bedside lung ultrasound

Ancillary facility construction

Medical insurance

Availability of data and materials

Abbreviations

Acknowledgements

Author information

Contributions

Corresponding author

Ethics declarations

Consent for publication

Competing interests

Additional information

Supplementary Information

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Epidural analgesia in labour and neonatal respiratory distress: a case-control study

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