An Evidence-Based Discussion of Fetal Pain and Stress.

BACKGROUND: The concept of fetal pain results from procedures conducted without anesthesia in preterm newborns and fetuses, which indicate that it is possible to examine fetal pain based on stress hormone, metabolic, and behavioral changes. Anatomical and physiological data suggest that fetuses become capable of processing nociceptive stimuli around midgestation, although the associated changes in fetal brain development remain unclear. What constitutes fetal pain remains controversial in the light of the definition of pain adopted by the International Association for the Study of Pain (IASP), which posits pain as an "unpleasant sensory and emotional experience." SUMMARY: Here, we examine the notion that human fetuses cannot "experience" pain and potential implications of this claim. We highlight the key scientific evidence related to fetal pain, including clinical studies on pain in fetuses and preterm newborns. We argue that consistent patterns of stress hormones, metabolic changes, body movements, hemodynamic changes, and pain-related facial expressions in fetuses exposed to invasive procedures overcome the need for subjective proof of pain as articulated in the IASP definition. No study to date has conclusively proven the absence of fetal pain beyond the age of viability. KEY MESSAGES: Based on the current evidence, we propose that all fetuses receive anesthesia regardless of the invasive procedures being performed to guarantee the least possible pain and physiological, behavioral, or hormonal responses without exposing the mother or her baby to unnecessary complications.

Physical and social activities constraint and its effects on Body Mass Index of former Neonatal Intensive Care children.

OBJECTIVE: It is reported weight gain in children due to the confinement measures during the Covid-19 pandemic. We aimed to describe the effect of these measures on the nutritional status of former Neonatal Intensive Care Unit children. METHODS: Cross-sectional study, including former Neonatal Intensive Care Unit children. The outcome was the Body mass index (BMI). RESULTS: We enrolled 126 children (74.6 % preterm; 31 % small-for-gestational-age). Weight excess was greater in the youngest group (≤5 years: 33.8 %; >5 years: 15.2 %). Prematurity was associated with weight excess in both groups (≤5 years: p value 0.006; >5 years: p value 0.046; Pearson test). Mealtime changes, lack of physical activity, socioeconomic factors and the perinatal morbidities significantly influenced the mean BMI. Birth length Z score less than -1.28 was negatively associated with BMI, while gestational age at birth presented a positive association with BMI (linear regression model). CONCLUSIONS: The BMI increase due to the confinement measures associated with the gestational age at birth and in those born with intrauterine growth restriction is a matter of concern, as it might indicate a risk for future obesity.

Parents and healthcare professionals' attitudes to Kangaroo Care for preterm infants in the United Kingdom.

AIM: To explore the attitudes of parents and healthcare professionals (HCPs), and facilitators and barrier to implementation of Kangaroo Care (KC) in the United Kingdom. METHODS: Online cross-sectional survey; distributed via the British Association of Perinatal Medicine, Bliss (UK-based charity), social media. RESULTS: Sixty HCPs responded. 37 (62%) were nurses/nurse practitioners. 57 (95%) regularly implement KC. The most important factor that supported KC implementation was the team's belief in benefits of KC. Increased workload, staff shortage and fear about safely of KC in unwell infants were recognised as the challenges preventing implementation. Five hundred eighteen parents responded. 421 (81%) had a preterm baby within 3 years. 338 (80%) were familiar with KC. The main facilitator was the belief that their baby enjoyed it. Excess noise and crowding on the unit were the most frequently reported barriers. Lack of opportunity and limited staff support were the main reasons why they had been unable to practice KC. CONCLUSION: We found that most HCPs and parents believe that KC is beneficial and would like to practice it. Lack of resources to enable effective implementation is the main barrier. Service development and implementation research is required to ensure that KC is delivered in all UK neonatal units.

Association of preterm birth with poor metabolic outcomes in schoolchildren.

OBJECTIVE: To investigate, at school age, the metabolic profile of children born preterm. METHODS: A cross-sectional study of children 5 to 8 years old, born with gestational age (GA) < 34 weeks and/or weight ≤ 1,500 grams. Clinical and anthropometric data were assessed by a single trained pediatrician. Biochemical measurements were done at the organization's Central Laboratory using standard methods. Data on health conditions, eating, and daily life habits were retrieved from medical charts and through validated questionnaires. Binary logistic and linear regression models were built to identify the association between variables, weight excess, and GA. RESULTS: Out of 60 children (53.3% female), 6.8 ± 0.7 years old, 16.6% presented excess weight, 13.3% showed increased insulin resistance markers and 36.7% had abnormal blood pressure values. Those presenting excess weight had higher waist circumferences and higher HOMA-IR than normal-weight children (OR = 1.64; CI = 1.035-2.949). Eating and daily life habits were not different among overweight and normal-weight children. The small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA, 83.3%) birth weight children did not differ regarding clinical (body weight, blood pressure) or biochemical variables (serum lipids, blood glucose, HOMA-IR). CONCLUSION: Schoolchildren born preterm, regardless of being AGA or SGA, were overweight, and presented increased abdominal adiposity, reduced insulin sensitivity, and altered lipid profile, justifying longitudinal follow-up regarding adverse metabolic outcomes in the future.

Risk factors for hemodynamically significant patent ductus arteriosus in preterm infants requiring surgical ligation: a nested case-control study / 中华实用儿科临床杂志

Objective:To analyze the risk factors for premature infants with hemodynamically significant patent ductus arteriosus (hs-PDA) requiring surgical treatment, and to explore the indications for surgical treatment in premature infants with hs-PDA.Methods:A nested case-control study was conducted.The data of premature infants with gestational age<30 weeks who were diagnosed with hs-PDA in the Neonatal Intensive Care Unit of Peking Union Medical College Hospital from January 2007 to May 2020 were analyzed retrospectively.The hs-PDA patients treated surgically were included in the operation group.The hs-PDA patients of the same gestational age and gender who were not treated surgically were taken as the control group.The ratio of the case number between the operation and control groups was 1∶2.The clinical data during pregnancy, at birth and after birth of premature infants were compared between the 2 groups.The measurement data were tested by the independent sample t test or Mann- Whitney U test.The classification and enumeration data were compared by the Fisher′ s exact probability method.The risk factors for premature infants with hs-PDA requiring surgical treatment were analyzed by the conditional Logistic regression method. Results:A total of 182 premature infants with hs-PDA were enrolled in the study, including 10 in the operation group and 20 in the control group.The patients underwent PDA ligation 30.5(22.7, 37.0) d after birth, and the median preo-perative invasive ventilation duration was 9.7(17.5, 27.2) d. Compared with the control group(20 cases), the preterm infants in the operation group had a lower birth weight [(891.5±118.0) g vs.(1 054.4±230.2) g, t=2.091], a wider arterial duct diameter [3.2(2.8, 4.0) mm vs.2.0(2.0, 3.0) mm, Z=-3.300], and longer invasive ventilation duration [25.0(18.7, 38.2) d vs.3.0(1.0, 7.5) d, Z=-3.688]. Besides, the operation group applied the pulmonary surfactant for more times [2(1, 3) times vs.1(1, 2) times, Z=-2.440], and inhaled a higher concentration of oxygen on the 14 th day after birth [29(25, 36)% vs.21(21, 29)%, Z=-2.358] than the control group.Moreover, compared with the control group, the operation group took longer to achieve adequate enteral feeding [48.2(51.5, 63.5) d vs.42.5(23.5, 48.0) d, Z=2.789], and gained a higher maximum vasoactive inotropic score (VIS) [3.0(0, 3.5) points vs.0(0, 0) points, Z=-2.630]. The difference in all the above-mentioned indicators between the 2 groups was statistically significant (all P<0.05). Univariate Logistic regression analysis showed that the arterial duct diameter, application times of the pulmonary surfactant, the maximum VIS score, and the time taken to achieve sufficient enteral feeding were all related to the need for surgical treatment of hs-PDA in the operation group (all P<0.05). Multivariate Logistic regression analysis revealed that the invasive ventilation duration ( OR=0.747, 95% CI: 0.560-0.998, P=0.048) was an independent risk factor for hs-PDA premature infants requiring surgical treatment. Conclusions:The factors related to the need for surgical treatment in preterm infants with hs-PDA include a wide arterial duct diameter, multiple applications of the pulmonary surfactant, a high concentration of inhaled oxygen on the 14 th day, and the long time to achieve sufficient enteral feeding.The independent risk factor for the surgical treatment in hs-PDA children is the long invasive ventilation duration.

Clinical research of less invasive surfactant administration combined with nasal intermittent positive pressure ventilation in preterm infants with respiratory distress syndrome / 中华急诊医学杂志

Objective:To evaluate the efficacy and safety of less invasive surfactant administration (LISA) combined with nasal intermittent positive pressure ventilation (NIPPV) in the treatment of infants with respiratory distress syndrome (RDS).Methods:A prospective study was conducted on preterm infants of gestational age ≤34 weeks with RDS who were admitted to the Neonatal Intensive Care Unit of Xuzhou Central Hospital from October 2019 to November 2021. The infants were randomly assigned into the LISA+NIPPV group and the intubation-surfactant-extubation (INSURE) +nasal continuous positive airway pressure (NCPAP) group. In the LISA+NIPPV group, with the support of NIPPV, a Lisa tube was inserted through the vocal cords under direct vision with direct laryngoscope, and then pulmonary surfactant (PS) was infused into the lung. In the INSURE+NCPAP group, the patients were endotracheally intubated and infused with PS into the lung through endotracheal tube, then extubated and continued to receive NCPAP therapy (INSURE). The blood gas analysis at 1 h and 6 h after PS infusion, the adverse reactions during injection, clinical efficacy, bronchopulmonary dysplasia (BPD) and other related complications were compared between the two groups.Results:A total of 112 preterm infants with RDS were enrolled, including 58 in the LISA+NIPPV group and 54 in the INSURE+NCPAP group. The blood oxygen partial pressure (PaO 2) and PaO 2/FiO 2 (P/F) in the LISA+NIPPV group were significantly higher than those in the INSURE+NCPAP group at 1 h and 6 h after PS infusion, while carbon dioxide partial pressure (PaCO 2) were significantly lower than that in the INSURE+NCPAP group, and the differences were statistically significant (all P<0.05). The rate of tracheal intubation within 72 h (15.5% vs. 33.3%), the duration of non-invasive ventilation [ (7.5 ± 4.3) d vs.(9.9 ± 5.5) d ], total oxygen inhaling [ (10.5 ± 3.5) d vs.(13.3 ± 4.1) d ], failure rate of machine withdrawal (8.6% vs. 31.0% ), the times of apnea [7.0 (3.0-21.0) times vs. 15.0 (4.0-28.0) times ] and re-administration of PS (17.2% vs. 33.3%) in the LISA+NIPPV group were significantly lower than those in the INSURE+NCPAP group, and the differences were statistically significant ( P<0.05). The incidence of regurgitation in the LISA+NIPPV group was lower than that in the INSURE+NCPAP group (13.8% vs. 35.2%), and the difference was statistically significant ( P<0.05). There was no significant difference in the time needed for intubation between the two groups ( P>0.05). The occurrence of BPD in the LISA+NIPPV group was significantly lower than that in the INSURE+NCPAP group (10.3% vs. 25.9%), and there was no significant difference in other related complication between the two groups (all P>0.05). Conclusions:LISA combined with NIPPV in the treatment of preterm infants with RDS can effectively improve oxygenation, reduce carbon dioxide retention, reduce the mechanical ventilation rate, shorten the duration of noninvasive mechanical ventilation, and reduce the incidence of BPD.

Association of preterm birth with poor metabolic outcomes in schoolchildren

Abstract Objective: To investigate, at school age, the metabolic profile of children born preterm. Methods: A cross-sectional study of children 5 to 8 years old, born with gestational age (GA) < 34 weeks and/or weight ≤ 1,500 grams. Clinical and anthropometric data were assessed by a single trained pediatrician. Biochemical measurements were done at the organization's Central Laboratory using standard methods. Data on health conditions, eating, and daily life habits were retrieved from medical charts and through validated questionnaires. Binary logistic and linear regression models were built to identify the association between variables, weight excess, and GA. Results: Out of 60 children (53.3% female), 6.8 ± 0.7 years old, 16.6% presented excess weight, 13.3% showed increased insulin resistance markers and 36.7% had abnormal blood pressure values. Those presenting excess weight had higher waist circumferences and higher HOMA-IR than normal-weight children (OR = 1.64; CI = 1.035-2.949). Eating and daily life habits were not different among overweight and normal-weight children. The small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA, 83.3%) birth weight children did not differ regarding clinical (body weight, blood pressure) or biochemical variables (serum lipids, blood glucose, HOMA-IR). Conclusion: Schoolchildren born preterm, regardless of being AGA or SGA, were overweight, and presented increased abdominal adiposity, reduced insulin sensitivity, and altered lipid profile, justifying longitudinal follow-up regarding adverse metabolic outcomes in the future.

Determinantes do contexto familiar relacionados ao cuidado das crianças prematuras, segundo o modelo bioecológico / Determinants of the family context related to the care of premature children, according to the bioecological model

Resumo: Trata-se de um estudo qualitativo, descritivo, do tipo estudo de casos múltiplos, embasado no referencial metodológico de Yin, que teve como objetivo descrever os determinantes do contexto familiar relacionados ao cuidado de crianças prematuras, segundo o Modelo Bioecológico. Realizado em um município do Estado do Paraná, Brasil, entre setembro de 2021 e março de 2022, com famílias de crianças prematuras egressas da unidade neonatal, até um ano de idade corrigida, que realizaram o acompanhamento de crescimento e desenvolvimento no ambulatório de puericultura da instituição de saúde selecionada para este estudo. Obteve-se a participação de 18 famílias. A coleta de evidências ocorreu por meio de entrevistas on-line, e utilizou-se ferramentas como genogramas e ecomapas que ajudaram, de forma sistemática e organizada, a ampliar o conhecimento do contexto familiar, sua estrutura, forças e recursos. Na organização dos dados, utilizou -se o Software Web Qualitative Data Analysis, para posteriormente serem analisados à luz do marco teórico do Modelo Bioecológico de Urie Bronfenbrenner. Da análise, emergiram duas categorias temáticas que explicitam a influência bidirecional e sinergia entre a criança em desenvolvimento e o seu contexto. A categoria organização do sistema familiar, contempla a composição, características biopsicossociais, organização e funcionamento do sistema familiar. A segunda categoria, recursos do sistema familiar, compreende o acesso a serviços públicos, bens materiais e econômicos da família, além do estabelecimento da rede de apoio social como recurso para o cuidado da criança prematura. Ao estudar o contexto familiar no seu ambiente mais íntimo e próximo à criança, foi possível perceber o impacto da prematuridade como situação vital no curso de vida, na dinâmica da família e no processo de construção do papel parental; ao mesmo tempo, a exploração das interações com outros microssistemas e o núcleo familiar permitiu o reconhecimento dos múltiplos aspectos do contexto que se tornaram determinantes para facilitar ou dificultar o cuidado infantil, desde a gravidez, o nascimento e após a alta da unidade neonatal. Nessa perspectiva, esta abordagem disponibiliza uma visão ecologicamente válida que permite identificar aqueles determinantes potencialmente modificáveis, subsidiando informações relevantes para os profissionais da saúde priorizar e orientar os cuidados e suporte social, com vista a propor e manter contextos saudáveis e promotores do bem-estar da família, a saúde e o desenvolvimento integral das crianças prematuras.

Abstract: This is, a qualitative, a descriptive multiple-case study grounded in Yin's methodological framework, which aimed to describe the family context determinants related to the care of preterm babies, according to the Bioecological Model. It was conducted in a municipality of Parana State, Brazil, between september 2021 and march 2022, with families of infant preterm, whose were discharged from a neonatal unit, children until one year of corrected age and, whose growth and development were followed up at the childcare outpatient unit of the healthcare institution selected for this study. 18 families participated in the study. Data collection was carried out by means of online interviews, and some tools were used, such as genograms and ecomaps, which helped, in a systematic and organized way, to expand knowledge of the family context, its structure, strengths and resources. For data organization, the Web Qualitative Data Analysis, Software, was used for further data analysis in light of the Bioecological Model by Urie Bronfenbrenner. From the analysis, two thematic categories emerged, which clarified the bidirectional influence and synergy between the developing child and his/her context. The family system organization category, contemplates the composition, biopsychosocial characteristics, organization and functioning of the family system. The second category, family system resources, comprises the access to public services, family's material and economic resources, apart from the establishment of a social support network as a resource to take care of the premature child. By studying the family context in its inner and closest environment to the child, it was possible to perceived the impact of prematurity as a vital situation in the course of life, in the dynamics of the family and in the process of building the parental role; at the same time, the exploration of interaction with other microsystems and the nuclear family enabled the recognition of the multiple aspects of the context that became determinants to facilitate or hinder child care, from pregnancy, birth and after discharge from the neonatal unit. In this perspective, this approach provides an ecologically valid view, that allows to identify those potentially modifiable determinants, underpinning relevant information for health care professionals to be able to prioritize and guide care and social support, in order to propose and keep healthy contexts, which promote the well-being of the family, health and integral development of premature children.

Evidence summary on the management of the developmentally supportive environment in the neonatal intensive care unit / 中华实用儿科临床杂志

Objective:To retrieve, evaluate and integrate relevant evidence on the management of the developmentally supportive environment in the neonatal intensive care unit(NICU), and to provide clinical references.Methods:Evidence on NICU environmental management was retrieved from Guidelines International Network, Joanna Briggs Institute, National Institute for Health and Care Excellence, Scottish Intercollegiate Guide Network, National Guideline Clearinghouse, Registered Nurses′ Association of Ontario, Yimaitong and other Websites, BMJ Best Practice, UpToDate, Cochrane Library, PubMed, Embase, Wanfang Database, CNKI and other database.The evidence included guidelines, evidence summaries, best clinical practice manuals, expert consensus and systematic reviews.The date limit was from the establishment of the databases to March 31, 2021.Results:Totally 16 articles were involved, including 4 guidelines, 9 systematic reviews, and 3 expert consensus.Finally, 20 pieces of best evidence on four aspects were su-mmarized: sound, light, touch, and smell.There were 11 A-level recommendations and 9 B-level recommendations.The evidence suggested that health care workers should reduce noise and protect premature infants from being exposed to bright light, noxious gases, and negative touch stimuli.Besides, benign auditory and olfactory stimuli, circadian light, and mother-infant skin-to-skin contact should be used to promote the development of premature infants.Conclusions:This study is a summary of the recommendations on NICU environmental management.It is well-designed and has achieved fruitful results, showing great significance for reducing environmental stress of premature infants in the NICU.However, the current recommended methods for providing benign stimulation require validation of more high-quality, well-designed research.It is recommended that medical staff should selectively apply the evidence to clinical practice according to the actual situation.

Clinical research of the LISA technique combined with caffeine in the treatment of respiratory distress syndrome in preterm infants / 中华急诊医学杂志

Objective:To evaluate the efficacy and safety of less invasive surfactant administration (LISA) combined with caffeine citrate in the treatment of respiratory distress syndrome (RDS) in preterm infants receiving continuous positive airway pressure (NCPAP) ventilation.Methods:From August 2019 to April 2021, a total of 112 preterm infants with RDS (26 weeks≤gestational age ≤32 weeks) who were hospitalized in the Neonatal Intensive Care Unit of Xuzhou Central Hospital, were chosen as research subjects. The patients were randomly divided into the LISA combined treatment group ( n=58) and the INSURE group ( n=54). In the LISA combined treatment group, a LISA tube was inserted through the vocal cords under direct vision with a direct laryngoscope and then infused with pulmonary surfactant (PS) into the lung when NCPAP ventilation was applied, and caffeine citrate was given intravenously. In the INSURE group, the patients were endotracheally intubated and infused with PS into the lung through an endotracheal tube, and then extubated and put on NCPAP again. The following indicators were examined: the general clinical data, results of blood gas analysis at 1 h and 6 h after infusion of PS into the lung, clinical efficacy and related complications. Results:①No significant differences were found between the two groups in the general clinical data (all P>0.05).Intra-group comparison within LISA combined treatment group or INSURE group showed that partial pressure of arterial carbon dioxide (PaCO 2), partial pressure of arterial oxygen (PaO 2) of blood gas analysis and PaO 2/fraction of inspired oxygen (P/F) at 1 h and 6 h after infused PS into the lung were all improved compared to those of before treatment, and the differences were statistically significant (all P<0.05). The PaO 2 and P/F in the LISA combined treatment group at 1 h and 6 h after breath support therapy were higher than those in the INSURE group, while PaCO 2 was lower than that in the INSURE group, and the differences were statistically significant (all P<0.05). The duration of noninvasive ventilation, total oxygen inhalation, re-administration of PS, failure rate of machine withdrawal, the rate of tracheal intubation within 72 h and the times of apnea in the LISA combined treatment group were significantly shorter, or lower, or less than those in the INSURE group [3.0 (1.0, 18.0) d vs. 7.5 (2.0, 22.0) d, 5.5 (3.0, 21.0) d vs. 10.5 (4.0, 28.0) d, 9 (15.5%) vs. 17 (31.5%), 6 (10.3%) vs. 14 (25.9%), 5 (8.6%) vs. 12 (22.2%), 5.0 (3.0, 21.0) times vs. 15.0 (4.0, 28.0) times], and the differences were all statistically significant (all P<0.05). The incidence of bronchopulmonary dysplasia in the LISA combined treatment group was less than that in the INSURE group [(5 (8.6%) vs. 13 (24.1%)], and the difference was statistically significant ( P<0.05). There was no significant difference between the two groups in other complications( P>0.05). Conclusions:Compared with INSURE, the LISA technique combined with caffeine citrate can effectively improve oxygenation, reduce the mechanical ventilation rate, shorten the duration of noninvasive mechanical ventilation, and reduce the incidence of BPD in the treatment of premature infants with RDS at the gestational age of 26-32 weeks.

Interpretation of outpatient respiratory management of infants, children, and adolescents with post-prematurity respiratory disease: an official American Thoracic Society clinical practice guideline / 中华实用儿科临床杂志

In recent years, the management of respiratory diseases related to preterm birth has received extensive attention.In 2021, the American Thoracic Society brought together multidisciplinary experts in respiratory, neonato-logy, otolaryngology, sleep medicine, radiology and nursing specialties to develop Guidelines for outpatient respiratory management in infants, children, and adolescents with post-preterm respiratory disease (hereinafter referred to as the " Guideline" ), aiming to provide evidence-based medical evidence for standardized outpatient management of respiratory diseases associated with preterm birth at different ages.The Guideline was interpreted and summarized so that pediatric clinicians could correctly diagnose and treat these diseases, and understand and implement standardized outpatient management on the basis of evidence.

The correlation between γδ-T lymphocyte subset in early postnatal peripheral blood and brain injury of preterm infants / 中华实用儿科临床杂志

Objective:To investigate the correlation between preterm infants with brain injury and the proportion of lymphocyte subsets, especially γδ-T cells in the postnatal peripheral blood, and to determine the predictive potential of γδ-T cells in the early peripheral blood in brain injury.Methods:It was a prospective study involving 106 preterm infants with gestational age less than 34 weeks who were delivered in the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University from January 1, to June 1, 2021.Relative levels of γδ-T , CD4 + T, CD8 + T, CD3 + T and total lymphocyte subsets in peripheral blood collected within the first 24 hours after birth were measured by flow cytometry.Recruited infants were divided into brain injury group (36 cases) and non-brain injury group (70 cases) according to serial cranial ultrasound and magnetic resonance imaging(MRI) at the corrected gestational age of 36-37 weeks.Differences in general conditions and the proportion of lymphocyte subsets between groups were compared by the t-test or Chi- square test.Patients in brain injury group were further divided into intracranial hemorrhage(ICH) group(8 cases), periventricular leukomalacia (PVL) group (6 cases)and diffuse white matter damage (WMD) group(22 cases). The proportion of lymphocyte subsets among the different groups was compared by One- Way ANOVA, followed by the LSD- t test. Results:The proportion of γδ-T cells in postnatal peripheral blood of preterm infants at 24 hours after birth in brain injury group was significantly lower than that of non-brain injury group [(0.09±0.12)% vs.0.15±0.13)%, t=-2.445, P=0.016]. No significant differences in the proportion of the CD4 + and CD8 + T cell subsets were found between them.Both preterm infants in PVL group and WMD group had a significantly lower proportion of γδ-T cells at 24 hours after birth compared to that of the non-brain injury group [(0.03±0.05)%, (0.07±0.09)% and (0.15±0.13)%], respectively, ( t=-2.190, -2.659, all P<0.05). Conclusions:γδ-T cells in early postnatal peripheral blood may be involved in the development of brain injury in preterm infants and they had early predictive value for preterm infants at high risk of brain injury, especially the leukomalacia and diffuse white matter injury.

Automation of oxygen titration in preterm infants: Current evidence and future challenges.

For the preterm infant with respiratory insufficiency requiring supplemental oxygen, tight control of oxygen saturation (SpO2) is advocated, but difficult to achieve in practice. Automated control of oxygen delivery has emerged as a potential solution, with six control algorithms currently embedded in commercially-available respiratory support devices. To date, most clinical evaluations of these algorithms have been short-lived crossover studies, in which a benefit of automated over manual control of oxygen titration has been uniformly noted, along with a reduction in severe SpO2 deviations and need for manual FiO2 adjustments. A single non-randomised study has examined the effect of implementation of automated oxygen control with the CLiO2 algorithm as standard care for preterm infants; no clear benefits in relation to clinical outcomes were noted, although duration of mechanical ventilation was lessened. The results of randomised controlled trials are awaited. Beyond the gathering of evidence regarding a treatment effect, we contend that there is a need for a better understanding of the function of contemporary control algorithms under a range of clinical conditions, further exploration of techniques of adaptation to individualise algorithm performance, and a concerted effort to apply this technology in low resource settings in which the majority of preterm infants receive care. Attainment of these goals will be paramount in optimisation of oxygen therapy for preterm infants globally.

Targeting Treatments to Health Disparities.

These initial data suggest that with prenatal vitamins and choline supplements, we might decrease one risk factor associated with poorer health outcomes disproportionally affecting Black families, ie, preterm birth. Dissemination of this research fulfills the principle of Justice in the Belmont Report, to ensure that participants from different racial, ethnic and socioeconomic groups receive benefits from research directed to their specific problems.

Prescrição de medicamentos off-label e sem licença para prematuros de unidade de terapia intensiva neonatal / Prescription of off-label and unlicensed drugs for preterm infants in a neonatal intensive care unit

RESUMO Objetivo: Avaliar o uso de medicamentos off-label e sem licença em recém-nascidos prematuros hospitalizados em unidade de terapia intensiva neonatal. Métodos: Estudo de coorte não concorrente, incluindo prematuros admitidos em três unidades de terapia intensiva neonatais, nos anos de 2016 e 2017, acompanhados durante o período neonatal. O uso de medicamentos e o número foram registrados para todo o período e classificados segundo a Anatomical Therapeutic Chemical. Foram realizadas análises descritivas e bivariadas dos dados para avaliar associações entre o número de medicamentos utilizados (total, off-label e sem licença) e as variáveis explicativas de interesse. Resultados: Os 400 neonatos prematuros utilizaram 16.143 medicamentos, com 86 especialidades diferentes; 51,9% desses itens foram classificados como off-label e 23,5% como sem licença. Os mais prescritos foram gentamicina e ampicilina (17,5% e 15,5% dos off-label, respectivamente) e cafeína (75,5% dos não licenciados). O estudo demonstrou associações significativas do uso de medicamentos off-label com a menor idade gestacional, baixo peso ao nascer, menor escore de Apgar no quinto minuto, manobra de reanimação avançada em sala de parto e óbito. Com os medicamentos não licenciados, foram verificadas associações com a menor idade gestacional, baixo peso ao nascer e escore de Apgar no quinto minuto menor que 7. Conclusão: Os neonatos internados em unidades de terapia intensiva neonatais são muito expostos ao uso de medicamentos off-label e sem licença. Tornam-se necessários mais investimentos em estudos para alcançar maior segurança e qualidade da terapêutica medicamentosa empregada em neonatologia.

ABSTRACT Objective: To evaluate the use of off-label and unlicensed medications in preterm infants hospitalized in a neonatal intensive care unit. Methods: This nonconcurrent cohort study included preterm infants admitted to 3 neonatal intensive care units in 2016 and 2017 who were followed up during the neonatal period. The type and number of medications used were recorded for the entire period and classified based on the Anatomical Therapeutic Chemical. Descriptive and bivariate data analyses were performed to assess associations between the number of drugs used (total, off-label and unlicensed) and the explanatory variables of interest. Results: Four hundred preterm infants received 16,143 prescriptions for 86 different pharmaceuticals; 51.9% of these medications were classified as off-label and 23.5% as unlicensed. The most prescribed drugs were gentamicin and ampicillin (17.5% and 15.5% among off-label, respectively) and caffeine (75.5% among unlicensed). The results indicated significant associations between the use of off-label drugs and lower gestational age, low birth weight, lower 5-minute Apgar score, advanced resuscitation maneuver in the delivery room and death. The prescription of unlicensed drugs was associated with lower gestational age, low birth weight and 5-minute Apgar score below 7. Conclusion: Neonates admitted to neonatal intensive care units are highly exposed to off-label and unlicensed medications. Further studies are needed to achieve greater safety and quality of drug therapy used in neonatology.

The implications of routine milk fortification for the short and long-term health of preterm babies.

Fortification refers to the practice of enriching human milk feeds for very preterm babies with macronutrients, minerals and vitamins. Though standard of care in some parts of the world, adoption of fortification is not universal. Fortification entered into use on the assumption that human milk macronutrient content, principally protein, is insufficient to support the growth and development of very preterm babies. However, because of the substantial variability in human milk composition, routine fortification risks exposing some babies to very high protein intakes, which may be dangerous. Some clinicians fear fortification with cow-milk derived products will increase the risk of necrotising enterocolitis, leading them to favour commercial fortifiers made from pooled human milk over cow milk based products, a practice that has additional ethical implications. Randomised controlled trials of multi-nutrient fortification to-date are inadequate. No trial has had power to detect important functional effects; the majority are methodologically weak and focus primarily upon short-term growth. Evidence to guide practice is inadequate. There is an urgent need for collaboration to conduct high-quality research to end these long-standing uncertainties.

Black American Maternal Prenatal Choline, Offspring Gestational Age at Birth, and Developmental Predisposition to Mental Illness.

Black Americans have increased risk for schizophrenia and other mental illnesses with prenatal origins. Prenatal choline promotes infant brain development and behavioral outcomes, but choline has not been specifically assessed in Black Americans. Pregnant women (N = 183, N = 25 Black Americans) enrolled in a study of prenatal stressors and interactions with prenatal choline. Black American women had lower 16-week gestation plasma choline than Whites. Lower choline was not related to obesity, income, or metabolic genotypes. Pregnant women in rural Uganda have higher choline levels than Black American women. Black Americans' lower choline was associated with higher hair cortisol, indicative of higher stress. Lower maternal choline was associated with offsprings' lower gestational age at birth and with decreased auditory P50 inhibition, a marker of inhibitory neuron development. Behavioral development was assessed on the Infant Behavior Questionnaire-R-SF (IBQ-R) at 3 months. Lower Black American maternal gestational choline was associated with lower infant IBQ-R Orienting/Regulation, indicating decreased attention and relation to caregivers. Additional evidence for developmental effects of choline in Black Americans comes from a randomized clinical trial of gestational phosphatidylcholine supplementation versus placebo that included 15 Black Americans. Phosphatidylcholine increased gestational age at birth and newborn P50 inhibition and decreased Social Withdrawn and Attention problems at 40 months of age in Black Americans' offspring compared to placebo. Inhibitory and behavioral deficits associated with lower prenatal choline in offspring of Black American women indicate potential developmental predispositions to later mental illnesses that might be ameliorated by prenatal choline or phosphatidylcholine supplementation.

Kangaroo care for mothers and fathers of premature infants: a non-inferiority study / 中国实用护理杂志

Objective:To explore the effect of kangaroo care for mothers and fathers on preterm infants' heart rate, blood oxygen, body temperature and so on, and to explore the influence of kangaroo care on the anxiety of the implementers.Methods:Totally 132 cases of preterm infants and their parents from September 2017 to September 2018 in Shengjing Hospital of China Medical University were randomly divided into mother group (67 cases) and father group (65 cases) by envelope method. The intervention lasted for two hours. State Anxiety Inventory(SAI) was used to evaluate the anxiety status of the implementers before and after the intervention, and the heart rate, oxygen saturation and body temperature of preterm infants were recorded 15 minutes before and at the end of the intervention.Results:Before the intervention, the SAI scores of the two groups were 35.00(30.00, 45.00) in the mother group and 33.00(30.00, 43.00) in the father group, with no significant difference ( Z value was -0.645, P>0.05); after the intervention, the SAI score of the mother group was 29.00(23.00, 32.00) and that of the father group was 25.00(21.50, 28.00), with significant difference ( Z value was -3.518, P<0.01). Before and after the intervention, the changes of heart rate ( δ1=- 4.25), blood oxygen saturation ( δ2=1.45), body temperature ( δ3=0.20) of preterm infants before and after the intervention were tested by non inferiority test, and the difference was statistically significant ( t values were -6.370, 5.343, 12.612, P<0.01). Conclusions:The effect of kangaroo care on preterm infants' heart rate, blood oxygen and body temperature are no less than that of mothers. Compared with mother, kangaroo care can reduce father's anxiety better.

Fifteen-minute consultation: ABCDE approach to nutritional assessment in preterm infants / 中华围产医学杂志

The last 20 years has seen dramatic improvements in the survival of preterm infants due to improved antenatal and neonatal care. Closer attention to nutrition means early parenteral nutrition and mother's own milk are considered as standard of care. Many uncertainties remain however, such as optimal macronutrient intakes for longer term cognitive and metabolic outcomes, and the optimal probiotic regime to reduce the risk of necrotising enterocolitis. Nutrition involves macronutrients and micronutrients, immunonutrients, microbiomic aspects and nutrient delivery. It is also clear that there are behavioural and psychological aspects, and strongly held beliefs for parents and professionals that affect practice. While many healthcare professionals (HCPs) are aware of several key nutritional concepts on the neonatal intensive care unit (NICU), many HCPs lack a concise, systematic approach. This article provides a brief approach to nutritional assessment for use on the NICU summarised as ABCDE: A—anthropometry, B—biochemistry, C—clinical, D—dietary intakes, E—environment and evaluation.

Caffeine combined with heated humidified high-flow nasal cannula in the treatment of respiratory distress syndrome in preterm infants / 中华急诊医学杂志

Objective To observe the clinical efficacy and safety of caffeine citrate combined with heated humidified high-flow nasal cannula (HHHFNC) in the treatment of respiratory distress syndrome (RDS) in preterm infants.Methods From June 2017 to December 2018,a total of 82 preterm infants with RDS (28 weeks ≤ gestational age＜32 weeks) who were hospitalized in Neonatal Intensive Care Unit of the Affiliated Xuzhou Hospital of Southeast University were chosen as research subjects.They were randomly (random number table method) divided into two groups:the combined treatment group (n=42) and the control group (n=40).Infants in the combined treatment group were given caffeine citrate combined with HHHFNC,while infants in the control group were given nasal continuous positive airway pressure (NCPAP) without caffeine citrate.The general clinical data,results of blood gas analysis at 6 h and 24 h after breath support therapy,clinical efficacy,related complications and adverse drug reactions between the two groups were compared statistically by LSD-t test,Chi-square test and Kruskal-Wallis H rank sum test.Results ① No significant differences were found between the two groups in the general clinical data (all P＞0.05).② The results of intra-groups comparison within the combined treatment group or control group showed that the pH value,partial pressure of arterial carbon dioxide (PaCO2),partial pressure of arterial oxygen (PaO2) of blood gas analysis and PaO2/fraction of inspired oxygen (P/F) at 6 h and 24 h after breath support therapy were all significantly improved compared to those of before treatment (all P＜0.05);The PaO2 and P/F of premature infants in the combined treatment group at 6 h and 24 h after breath support therapy were significantly higher than those in the control group,while PaCO2 were significantly lower than that in the control group (all P＜0.05).③ The duration of noninvasive ventilation,total oxygen inhaling,failure rate of machine withdrawal,use of pulmonary surfactants,the rate of tracheal intubation within 72 h and the times of apnea in combined treatment group were 3.0 d (1.0,18.0)d,5.5 d (3.0,21.0)d,4 case(9.5％),10 case(23.8％),3 case(7.1％) and 6.0 times(3.0,21.0)times,which were significant shorter,or lower,or less than those in control group,which were 7.0 d (2.0,22.0),10.0 d (4.0,28.0),11 case(27.5％),19 case(47.5％),12 case(30.0％)and 15.0 times(4.0,28.0)times,and the differences were all statistically significant (all P＜0.05).④ The occurrence of nasal trauma,abdominal distention and head shaping in the combined treatment group were significantly lower than those in the control group (all P＜0.05).⑤ There were no significant differences between the two groups of premature infants in related complication and caffeine associated adverse reactions (all P＞0.05).Conclusions Caffeine citrate combined with HHHFNC treatment strategy for premature infants with RDS can effectively improve oxygenation,shorten the duration of noninvasive mechanical ventilation,increase the success rate of machine withdrawal,and reduce the incidence of nasal trauma and abdominal distention.