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IntroductionVery and extremely preterm infants frequently have brain injury-related long-term neurodevelopmental problems. Altered perfusion, for example, seen in the context of a hemodynamically significant patent ductus arteriosus (PDA), has been linked to injury of the immature brain. However, a direct relation with outcome has not been reviewed systematically.MethodsA systematic review was conducted to provide an overview of the value of different cerebral arterial blood flow parameters assessed by Doppler ultrasound, in relation to brain injury, to predict long-term neurodevelopmental outcome in preterm infants.ResultsIn total, 23 studies were included. Because of heterogeneity of studies, a meta-analysis of results was not possible. All included studies on resistance index (RI) showed significantly higher values in subjects with a hemodynamically significant PDA. However, absolute differences in RI values were small. Studies using Doppler parameters to predict brain injury and long-term neurodevelopmental outcome were inconsistent.DiscussionThere is no clear evidence to support the routine determination of RI or other Doppler parameters in the cerebral arteries to predict brain injury and long-term neurodevelopmental outcome in the preterm infant. However, there is evidence that elevated RI can point to the presence of a hemodynamically significant PDA.

Background Perinatal palliative care (PPC) is increasingly recognized as an essential component of quality maternity and neonatal care. Despite international calls for structured programs, little is known about how PPC is provided in everyday healthcare systems and how parents and professionals experience it. This study explored PPC practices in Flanders (Belgium), focusing on challenges and opportunities for improving care. Methods We conducted a qualitative study using semi-structured face-to-face interviews with healthcare professionals experienced in PPC, and with parents who had lost a child in the perinatal period. A total of 22 healthcare professionals and 18 parents participated. Framework analysis was employed to systematically analyze the interview data. The findings were compared with the results of a recent systematic review which synthesized existing literature and outlined the key components of PPC. Results In the absence of a formal PPC team, considerable effort was required to coordinate care and ensure effective information transfer between hospitals and departments. Palliative care training was largely informal, with most learning occurring on the job. In contrast to findings reported in the international literature, interview data revealed that external organizations were frequently and systematically involved in PPC. The recognizability of healthcare providers was identified as a key factor in parental psychosocial support. Parents’ expressions of gratitude, respect, and satisfaction were experienced by caregivers as highly supportive. In terms of shared decision-making, several parents expressed a need for clearer explanations of medical scenarios, more directive support from physicians, and early exploration of their preferred decision-making style. Simultaneously, both parents and professionals reported feeling limited by legal constraints. Additional needs included improved communication amongst all involved, greater structural support and infrastructure adapted to palliative care needs. Conclusions Both parents and healthcare providers pointed out the need for a multidisciplinary team to coordinate PPC across time and disciplines. Parents expressed more dissatisfaction with communication than with the purely medical aspects of care. The importance of caregiver introductions and role clarity, dedicated PPC training and experienced staff was stressed. A neutral, non-directive approach to decision-making did not suit all parents, underscoring the need to tailor support to individual preferences.

BackgroundThe optimal method to wean preterm infants from non-invasive respiratory support (NIVRS) with nasal continuous positive airway pressure (CPAP) or high-flow nasal cannula is still unclear, and methods used vary considerably between neonatal units.ObjectivePerform a systematic review and meta-analysis to determine the most effective strategy for weaning preterm infants born before 37 weeks’ gestation from NIVRS.MethodEMBASE, MEDLINE, CINAHL, Google and Cochrane Central Register of Controlled Trials were searched for randomised controlled trials comparing different weaning strategies of NIVRS in infants born before 37 weeks’ gestation.ResultsFifteen trials (1.547 infants) were included. With gradual pressure wean, the relative risk of successful weaning at the first attempt was 1.30 (95% CI 0.93 to 1.83), as compared with sudden discontinuation. Infants were weaned at a later postmenstrual age (PMA) (median difference (MD) 0.93 weeks (95% CI 0.19 to 1.67)). A stepdown strategy to nasal cannula resulted in an almost 3-week reduction in the PMA at successful weaning (MD −2.70 (95% CI −3.87 to −1.52)) but was associated with a significantly longer duration of oxygen supplementation (MD 7.80 days (95% CI 5.31 to 10.28)). A strategy using interval training had no clinical benefits. None of the strategies had any effect on the risk of chronic lung disease or the duration of hospital stay.ConclusionA strategy of gradual weaning of airway pressure might increase the chances of successful weaning. Stepdown strategy from CPAP to nasal cannula is a useful alternative resulting in an earlier weaning, but the focus should remain on continued weaning in order to avoid prolonged oxygen supplementation. Interval training should probably not be used.

Background Perinatal palliative care (PPC) provides essential support for families and healthcare providers at the end-of-life. Despite clear global need, structured PPC programs are not widely established. Aim To develop a PPC program that supports families confronted with a severe perinatal diagnosis for their (unborn) child, with a focus on evidence-based development of such program, ensuring care is effective, consistent, and aligned with best practices. Methods We systematically designed a PPC program following a 7-step method, using Bleijenberg’s extended Medical Research Council framework. We conducted a qualitative interview study with 22 healthcare providers and 18 bereaved parents from six hospitals to identify care gaps alongside an integrative review study of international programs. These combined findings informed the development of a PPC prototype program, intended to be integrated in routine practice. Subsequently, we refined the program, identified barriers to implementation, and explored opportunities for contextual tailoring through six participatory workshops involving both healthcare providers and bereaved parents at three hospitals. In these sessions we reviewed the preliminary care components, identified practical challenges, and adapted the model to align with local workflows, staffing realities, and documentation systems. Results Five core components were developed: Dedicated fixed PPC Team with care coordinators Formal/Specialized 1,5 day training covering essential PPC aspects Stepwise PPC Approach with a structured PPC plan including individualized care pathways and centralized resources and information sharing Proactive psychological support for both families and staff Structured Team Debriefings Key barriers to implementation included fragmented documentation systems, limited staffing and time resources, and challenges in cross-departmental coordination. Discussion We developed a PPC program based on existing international evidence and current PPC practices. This approach ensured both relevance and practical applicability. The program design is a strength, as it is grounded in evidence and shaped through active involvement of parents and healthcare providers, with attention to contextual tailoring. The program is now ready for pilot testing to assess feasibility and acceptability in clinical practice. Future implementation will require institutional support, contextual adaptation, and ongoing evaluation to ensure sustainable integration into perinatal care.

Background End-of-life decisions with potential life-shortening effect in neonates and infants are common. We aimed to evaluate how often and in what manner neonatologists consult with parents and other healthcare providers in these cases, and whether consultation is dependent on the type of end-of-life decision made. Methods Based on all deaths under the age of one that occurred between September 2016 and December 2017 in Flanders, Belgium, a nationwide mortality follow-back survey was performed. The survey asked about different types of end-of-life decisions, and whether and why parents and/or other healthcare providers had or had not been consulted. Results Response rate was 83% of the total population. End-of-life decisions in neonates and infants were consulted both with parents (92%) and other healthcare providers (90%), and agreement was reached between parents and healthcare providers in most cases (96%). When medication with an explicit life-shortening intent was administered parents were always consulted prior to the decision; however when medication without explicit life-shortening intention was administered parents were not consulted in 25% of the cases. Conclusions Shared decision-making between parents and physicians in case of neonatal or infant end-of-life decision-making is the norm in daily practice. All cases without parental consultation concerned non-treatment decisions or comfort medication without explicit life-shortening intention where physicians deemed the medical situation clear and unambiguous. However, we recommend to at least inform parents of medical options, and to explore other possibilities to engage parents in reaching a shared decision. Physicians consult other healthcare providers before making an end-of-life decision in most cases.

Background Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) less than 28 weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a PDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking. Methods This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA < 28 weeks) with an echocardiographic-confirmed PDA with a transductal diameter > 1.5 mm. Early treatment (between 24 and 72 h postnatal age) with the cyclooxygenase inhibitor (COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage ≥ IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36 weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis. Discussion As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28 weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36 weeks. Trial registration This trial is registered with the Dutch Trial Register NTR5479 (registered on 19 October 2015), the registry sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017–001376-28 .

When a severe diagnosis is made before or after birth, perinatal palliative care (PPC) can be provided to support the infant, parents and involved healthcare providers. An integrative and systematic overview of effectiveness and working components of existing PPC programs was needed. An integrative search was conducted in MEDLINE, Embase, CENTRAL, CINAHL, PsycInfo and Web of Science. Study designs examining the effect of PPC compared to regular care, and (empirical) articles describing the components of care included in existing PPC initiatives were included. Three independent authors reviewed titles, abstracts and full texts against eligibility criteria. PRISMA guidelines were followed; 21.893 records were identified; 69 publications met inclusion criteria. Twelve publications (17.4%) discussed the effect of a PPC program. Other publications concerned the description of PPC programs, most often by means of a program description (22/69; 31.9%), guidelines (14/769; 20.3%) or case study (10/69; 14.5%). Outcome measures envisioned four main target categories: care coordination, parents and family members, care for the fetus/neonate and healthcare providers. No trials exist to date. Analysis of working components revealed components related to changes directed to the policy of the hospital wards and components involving actual care being provided within the PPC program, directed to the fetus or infant, the family, involved healthcare providers or external actors. PPC is a growing research field where evidence consists mainly of descriptive studies and guidelines. The extensive list of possible PPC components can serve as a checklist for developing future initiatives worldwide. PPC includes several important actors: the fetus/infant and their family and included healthcare providers on both maternity and neonatal wards. This leads to a large variety of possible care components. However, while some studies show proof of concept, an evidence base to determine which components are actually effective is lacking.

Introduction Clinical nutrition for preterm and critically ill neonates remains a challenge. Preterms are often hemodynamically and metabolically compromised, which limits infusion volumes of nutrients and hinders achieving recommended nutrient intakes. While guidelines provide recommended ranges for parenteral nutrition (PN) intakes, they generally recommend enteral nutrition as soon as possible. Thus, in clinical practice, gradually increasing EN intakes complicates assessments of PN guideline adherence. Via a pragmatic approach, we assessed adherence to PN recommendations for macronutrients and energy as stated in the 2018 guidelines of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Methods In this retrospective study, we assessed the nutrition of preterm and critically ill term neonates from the neonatal intensive care unit of the University Hospital Brussels. We analyzed intakes for the first week of life, in which critically ill neonates at our center usually receive the majority of nutrients via PN. The PN-based provision of macronutrients and energy was analyzed descriptively in relation to the ESPGHAN 2018 recommendations. Results Macronutrients and energy provision gradually increased until they reached recommended or targeted values. Compared to term neonates, energy and lipid provision for preterms increased faster, while amino acid provision exceeded the ESPGHAN 2018 recommendations. Conclusions This study adds clinical practice data to the severely understudied field of the ESPGHAN 2018 PN guideline compliance. Using a pragmatic assessment of our nutrition protocols, we found the need to reduce the amount of amino acids per kg body weight per day to meet guideline recommendations.

Population and study design heterogeneity has confounded previous meta-analyses, leading to uncertainty about effectiveness and safety of elective high-frequency oscillatory ventilation (HFOV) in preterm infants. We assessed effectiveness of elective HFOV versus conventional ventilation in this group. We did a systematic review and meta-analysis of individual patients' data from 3229 participants in ten randomised controlled trials, with the primary outcomes of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age, death or severe adverse neurological event, or any of these outcomes. For infants ventilated with HFOV, the relative risk of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age was 0·95 (95% CI 0·88–1·03), of death or severe adverse neurological event 1·00 (0·88–1·13), or any of these outcomes 0·98 (0·91–1·05). No subgroup of infants (eg, gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids) benefited more or less from HFOV. Ventilator type or ventilation strategy did not change the overall treatment effect. HFOV seems equally effective to conventional ventilation in preterm infants. Our results do not support selection of preterm infants for HFOV on the basis of gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids. Nestlé Belgium, Belgian Red Cross, and Dräger International.

Background The death of a child before or shortly after birth is frequently preceded by an end-of-life decision (ELD). Population-based studies of incidence and characteristics of ELDs in neonates and infants are rare, and those in the foetal-infantile period (> 22 weeks of gestation – 1 year) including both neonates and stillborns, are non-existent. However, important information is missed when decisions made before birth are overlooked. Our study protocol addresses this knowledge gap. Methods First, a new and encompassing framework was constructed to conceptualise ELDs in the foetal-infantile period. Next, a population mortality follow-back survey in Flanders (Belgium) was set up with physicians who certified all death certificates of stillbirths from 22 weeks of gestation onwards, and infants under the age of a year. Two largely similar questionnaires (stillbirths and neonates) were developed, pilot tested and validated, both including questions on ELDs and their preceding decision-making processes. Each death requires a postal questionnaire to be sent to the certifying physician. Anonymity of the child, parents and physician is ensured by a rigorous mailing procedure involving a lawyer as intermediary between death certificate authorities, physicians and researchers. Approval by medical societies, ethics and privacy commissions has been obtained. Discussion This research protocol is the first to study ELDs over the entire foetal-infantile period on a population level. Based on representative samples of deaths and stillbirths and applying a trustworthy anonymity procedure, the research protocol can be used in other countries, irrespective of legal frameworks around perinatal end-of-life decision-making.