Mental health, pain and tiredness in adults born very preterm or with very low birthweight.

AIM: Adults born preterm have increased risk of mental health problems and other neurodevelopmental conditions. We aimed to investigate associations of mental health with pain and tiredness in adults born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) and at term, and whether these associations are influenced by physical activity. METHODS: As part of an EU Horizon 2020 project, individual participant data from six prospective cohort studies were harmonised for 617 VP/VLBW and 1122 term-born participants. Mental health was assessed by the Achenbach System of Empirically Based Assessment Adult Self-Report. Pain and tiredness were harmonised based on specific items from self-reported questionnaires. Associations between mental health and pain or tiredness were explored by linear regression. RESULTS: An increase in the mental health scales internalising, externalising and total problems was associated with increased pain and tiredness in the preterm and term group alike. Results were maintained when adjusting for physical activity. CONCLUSION: The findings indicate that associations between mental health, pain and tiredness in adults are independent of gestation or birthweight. Future research should explore other potential mechanisms that may underlie the increased risk of mental health problems in the preterm population.

The NeoPACE study: study protocol for the development of a core outcome set for neonatal palliative care.

BACKGROUND: Neonatal death is the leading category of death in children under the age of 5 in the UK. Many babies die following decisions between parents and the neonatal team; when a baby is critically unwell, with the support of healthcare professionals, parents may make the decision to stop active treatment and focus on ensuring their baby has a 'good' death. There is very little evidence to support the clinical application of neonatal palliative care and/or end-of-life care, resulting in variation in clinical provision between neonatal units. Developing core outcomes for neonatal palliative care would enable the development of measures of good practice and enhance our care of families. The aim of this study is to develop a core outcome set with associated tools for measuring neonatal palliative care. METHOD: This study has four phases: (1) identification of potential outcomes through systematic review and qualitative interviews with key stakeholders, including parents and healthcare professionals (2) an online Delphi process with key stakeholders to determine core outcomes (3) identification of outcome measures to support clinical application of outcome use (4) dissemination of the core outcome set for use across neonatal units in the UK. Key stakeholders include parents, healthcare professionals, and researchers with a background in neonatal palliative care. DISCUSSION: Developing a core outcome set will standardise minimum reported outcomes for future research and quality improvement projects designed to determine the effectiveness of interventions and clinical care during neonatal palliative and/or end-of-life care. The core outcome set will provide healthcare professionals working in neonatal palliative and/or end-of-life support with an increased and consistent evidence base to enhance practice in this area. TRIAL REGISTRATION: The study has been registered with the COMET initiative ( https://www.comet-initiative.org/Studies/Details/1470 ) and the systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023451068).

'I don't want him to always be so far behind': Parental perceptions of child independence in the context of extreme prematurity; a qualitative study.

This study addresses the paucity of research on parents of extremely preterm adolescents (born <27 weeks of gestation) and their experiences within the framework of parental determinism. We conducted semi-structured interviews with twenty-two mothers and one father. Data were analysed thematically, revealing three overarching themes and eight subthemes shaping parental accounts. These themes centred on parental ambitions for their children, their perceptions of their child's abilities, and the parenting behaviours employed to support parental aspirations. Parents' actions were influenced by their ambitions and the belief that they could impact their child's future independence. While some parents adopted 'trusting', non-intensive parenting behaviours, those anticipating challenges for their child's future independence resorted to intensive parenting practices. These findings align with the concept of parental determinism, emphasising the perceived causal link between present parental actions and future child outcomes. In the context of extreme prematurity, a nuanced understanding of parental perceptions regarding their child's future independence aligned with a delicate balance between hope and realistic aspiration is crucial for enhancing parental support and well-being.

Myelination of preterm brain networks at adolescence.

Prematurity and preterm stressors severely affect the development of infants born before 37 weeks of gestation, with increasing effects seen at earlier gestations. Although preterm mortality rates have declined due to the advances in neonatal care, disability rates, especially in middle-income settings, continue to grow. With the advances in MR imaging technology, there has been a focus on safely imaging the preterm brain to better understand its development and discover the brain regions and networks affected by prematurity. Such studies aim to support interventions and improve the neurodevelopment of preterm infants and deliver accurate prognoses. Few studies, however, have focused on the fully developed brain of preterm born infants, especially in extremely preterm subjects. To assess the long-term effect of prematurity on the adult brain, myelin related biomarkers such as myelin water fraction and g-ratio are measured for a cohort of 19-year-old extremely preterm born subjects. Using multi-modal imaging techniques that combine T2 relaxometry and neurite density information, the results show that specific brain regions associated with white matter injuries due to preterm birth, such as the posterior limb of the internal capsule and corpus callosum, are still less myelinated in adulthood. Furthermore, a weak positive relationship between myelin water fraction values and Full-Scale Intelligence Quotient (FSIQ) scores was found in multiple brain regions previously defined as less myelinated in the Extremely Preterm (EPT) cohort. These findings might suggest altered connectivity in the adult preterm brain and explain differences in cognitive outcomes.

Recombinant fragment of human surfactant protein D to prevent neonatal chronic lung disease (RESPONSE): a protocol for a phase I safety trial in a tertiary neonatal unit.

INTRODUCTION: Chronic respiratory morbidity from bronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth and has consequences for later respiratory, cardiovascular and neurodevelopmental outcomes. The early phases of respiratory illness are characterised by rapid consumption of endogenous surfactant and slow replenishment. Exogenous surfactant is routinely administered to infants born before 28 weeks of gestation as prophylaxis. Endogenous surfactant includes four proteins, known as surfactant proteins (SPs) A, B, C and D. Current bovine-derived and porcine-derived surfactant preparations only contain SPs B and C. SP-D has a key role in lung immune homeostasis as part of the innate immune system. Laboratory studies using recombinant SP-D have demonstrated reduced inflammation, which may be a pathway to reducing the associated morbidity from BPD. RESPONSE uses a recombinant fragment of human SP D (rfhSP-D), in a phase I safety and dose-escalation trial as the first stage in determining its effect in humans. METHODS AND ANALYSIS: This is a single-centre, dose-escalation, phase I safety study aiming to recruit 24 infants born before 30 weeks gestation with respiratory distress syndrome. In addition to routine surfactant replacement therapy, participants will receive three doses of rfhSP-D via endotracheal route at either 1 mg/kg, 2 mg/kg or 4 mg/kg. The study uses a Bayesian continual reassessment method to make dose escalation decisions. Dose-limiting events (DLE) in this trial will be graded according to the published Neonatal Adverse Event Severity Score. The primary outcome of this study is to evaluate the safety profile of rfhSP-D across each dose level based on the profile of DLE to establish the recommended phase 2 dose (RP2D) of rfhSP-D. ETHICS AND DISSEMINATION: The RESPONSE study has received ethical approval from London-Brent NHS Research Health Authority ethics committee. Results from the study will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBERS: ISRCTN17083028, NCT05898633. PROTOCOL VERSION: RESPONSE Protocol V.4.0 24th July 2024.

Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): five-year outcomes of a randomised trial.

Background: Concerns remain over the long-term safety of vascular endothelial growth factor (VEGF) inhibitors to treat retinopathy of prematurity (ROP). RAINBOW is an open label randomised trial comparing intravitreal ranibizumab (in 0.2 mg and 0.1 mg doses) with laser therapy in very low birthweight infants (<1500 g) with ROP. Methods: Of 201 infants completing RAINBOW, 180 were enrolled in the RAINBOW Extension Study. At 5 years, children underwent ophthalmic, development and health assessments. The primary outcome was visual acuity in the better-seeing eye. The study is registered with ClinicalTrial.gov, NCT02640664. Findings: Between 16-6-2016 and 21-4-2022, 156 children (87%) were evaluated at 5 years. Of 32 children with no acuity test result, 25 had a preferential looking test, for 4 children investigators reported low vision for each eye, and in 3 further children no vision measurement was obtained. 124 children completed the acuity assessment, the least square mean (95% CI) letter score in the better seeing eye was similar in the three trial arms-66.8 (62.9-70.7) following ranibizumab 0.2 mg, 64.6 (60.6-68.5) following ranibizumab 0.1 mg and 62.1 (57.8-66.4) following laser therapy; differences in means: ranibizumab 0.2 mg v laser: 4.7 (95% CI: -1.1, 10.5); 0.1 mg v laser: 2.5 (-3.4, 8.3); 0.2 mg v 0.1 mg: 2.2 (-3.3, 7.8). High myopia (worse than -5 dioptres) in at least one eye occurred in 4/52 (8%) children following ranibizumab 0.2 mg, 8/55 (15%) following ranibizumab 0.1 mg and 11/45 (24%) following laser therapy (0.2 mg versus laser: odds ratio: 3.99 (1.16-13.72)). Ocular and systemic secondary outcomes and adverse events were distributed similarly in each trial arm. Interpretation: 5-year outcomes confirm the findings of the original RAINBOW trial and a planned interim analysis at 2 years, including a reduced frequency of high myopia following ranibizumab treatment. No effects of treatment on non-ocular outcomes were detected. Funding: Novartis Pharma AG.

The outcomes of children born to mothers with autoimmune rheumatic diseases.

Maternal autoimmune rheumatic diseases can influence the outcomes of children through several life stages. During pregnancy, maternal inflammation and autoantibodies can hinder fetal development and lead to growth restriction, preterm birth, and low birth weight; prematurity, especially at extreme gestational ages, can in turn impair future child health. Treatment with compatible immunomodulatory drugs and preventive medications aims to keep maternal disease under control and minimise the risk of adverse pregnancy outcomes. However, concerns have been raised about the effects of immunomodulatory drugs on neonatal conditions (ie, the risk of serious infections, inadequate responses to vaccinations, and organ toxicity) and long-term outcomes (metabolic and cardiovascular problems and neurodevelopmental disorders). Among the unmet needs of parents with autoimmune rheumatic diseases, there is the estimation of risk for the children to develop autoimmune disorders and the need for reassurance about parenting capacity while living with a chronic condition. This Series paper provides a comprehensive overview of the literature and guidance on discussing these topics with patients.