Recommendations for data collection in cohort studies of preterm born individuals - The RECAP Preterm Core Dataset.

BACKGROUND: Preterm birth (before 37 completed weeks of gestation) is associated with an increased risk of adverse health and developmental outcomes relative to birth at term. Existing guidelines for data collection in cohort studies of individuals born preterm are either limited in scope, have not been developed using formal consensus methodology, or did not involve a range of stakeholders in their development. Recommendations meeting these criteria would facilitate data pooling and harmonisation across studies. OBJECTIVES: To develop a Core Dataset for use in longitudinal cohort studies of individuals born preterm. METHODS: This work was carried out as part of the RECAP Preterm project. A systematic review of variables included in existing core outcome sets was combined with a scoping exercise conducted with experts on preterm birth. The results were used to generate a draft core dataset. A modified Delphi process was implemented using two stages with three rounds each. Three stakeholder groups participated: RECAP Preterm project partners; external experts in the field; people with lived experience of preterm birth. The Delphi used a 9-point Likert scale. Higher values indicated greater importance for inclusion. Participants also suggested additional variables they considered important for inclusion which were voted on in later rounds. RESULTS: An initial list of 140 data items was generated. Ninety-six participants across 22 countries participated in the Delphi, of which 29% were individuals with lived experience of preterm birth. Consensus was reached on 160 data items covering Antenatal and Birth Information, Neonatal Care, Mortality, Administrative Information, Organisational Level Information, Socio-economic and Demographic information, Physical Health, Education and Learning, Neurodevelopmental Outcomes, Social, Lifestyle and Leisure, Healthcare Utilisation and Quality of Life. CONCLUSIONS: This core dataset includes 160 data items covering antenatal care through outcomes in adulthood. Its use will guide data collection in new studies and facilitate pooling and harmonisation of existing data internationally.

Variation in follow-up for children born very preterm in Europe.

BACKGROUND: Children born very preterm (<32 weeks of gestation) face high risks of neurodevelopmental and health difficulties compared with children born at term. Follow-up after discharge from the neonatal intensive care unit is essential to ensure early detection and intervention, but data on policy approaches are sparse. METHODS: We investigated the characteristics of follow-up policy and programmes in 11 European countries from 2011 to 2022 using healthcare informant questionnaires and the published/grey literature. We further explored how one aspect of follow-up, its recommended duration, may be reflected in the percent of parents reporting that their children are receiving follow-up services at 5 years of age in these countries using data from an area-based cohort of very preterm births in 2011/12 (N = 3635). RESULTS: Between 2011/12 and 22, the number of countries with follow-up policies or programmes increased from 6 to 11. The policies and programmes were heterogeneous in eligibility criteria, duration and content. In countries that recommended longer follow-up, parent-reported follow-up rates at 5 years of age were higher, especially among the highest risk children, born <28 weeks' gestation or with birthweight <1000 g: between 42.1% and 70.1%, vs. <20% in most countries without recommendations. CONCLUSIONS: Large variations exist in follow-up policies and programmes for children born very preterm in Europe; differences in recommended duration translate into cross-country disparities in reported follow-up at 5 years of age.

Treating very preterm European infants with inhaled nitric oxide increased in-hospital mortality but did not affect neurodevelopment at 5 years of age.

AIM: We examined the outcomes of using inhaled nitric oxide (iNO) to treat very preterm born (VPT) infants across Europe. METHODS: This was a sub-study of the Screening to Improve Health in Very Preterm Infants in Europe research. It focused on all infants born between 22 + 0 and 31 + 6 weeks/days of gestation from 2011 to 2012, in 19 regions in 11 European countries. We studied 7268 infants admitted to neonatal care and 5 years later, we followed up the outcomes of 103 who had received iNO treatment. They were compared with 3502 propensity score-matched controls of the same age who did not receive treatment. RESULTS: All countries used iNO and 292/7268 (4.0%) infants received this treatment, ranging from 1.2% in the UK to 10.5% in France. There were also large regional variations within some countries. Infants treated with iNO faced higher in-hospital mortality than matched controls (odds ratio 2.03, 95% confidence interval 1.33-3.09). The 5-year follow-up analysis of 103 survivors showed no increased risk of neurodevelopmental impairment after iNO treatment. CONCLUSION: iNO was used for VPT patients in all 11 countries. In-hospital mortality was increased in infants treated with iNO, but long-term neurodevelopmental outcomes were not affected in 103 5-year-old survivors.

Apgar Score and Neurodevelopmental Outcomes at Age 5 Years in Infants Born Extremely Preterm.

Importance: The Apgar score is used worldwide as an assessment tool to estimate the vitality of newborns in their first minutes of life. Its applicability to estimate neurodevelopmental outcomes in infants born extremely preterm (EPT; <28 weeks' gestation) is not well established. Objective: To investigate the association between the Apgar score and neurodevelopmental outcomes in infants born EPT. Design, Setting, and Participants: This cohort study was conducted using data from the Effective Perinatal Intensive Care in Europe-Screening to Improve Health in Very Preterm Infants in Europe (EPICE-SHIPS) study, a population-based cohort in 19 regions of 11 European countries in 2011 to 2012. Clinical assessments of cognition and motor function at age 5 years were performed in infants born EPT and analyzed in January to July 2023. Exposures: Apgar score at 5 minutes of life categorized into 4 groups (0-3, 4-6, 7-8, and 9-10 points). Main Outcomes and Measures: Cognitive and motor outcomes were assessed using the Wechsler Preschool and Primary Scale of Intelligence test of IQ derived from locally normed versions by country and the Movement Assessment Battery for Children-Second Edition. Parents additionally provided information on communication and problem-solving skills using the Ages and Stages Questionnaire, third edition (ASQ-3). All outcomes were measured as continuous variables. Results: From the total cohort of 4395 infants born EPT, 2522 infants were live born, 1654 infants survived to age 5 years, and 996 infants (478 females [48.0%]) followed up had at least 1 of 3 outcome measures. After adjusting for sociodemographic variables, perinatal factors, and severe neonatal morbidities, there was no association of Apgar score with IQ, even for scores of 3 or less (ß = -3.3; 95% CI, -10.5 to 3.8) compared with the score 9 to 10 category. Similarly, no association was found for ASQ-3 (ß = -2.1; 95% CI, -24.6 to 20.4). Congruent results for Apgar scores of 3 or less were obtained for motor function scores for all children (ß = -4.0; 95% CI, -20.1 to 12.1) and excluding children with a diagnosis of cerebral palsy (ß = 0.8, 95% CI -11.7 to 13.3). Conclusions and Relevance: This study found that low Apgar scores were not associated with longer-term outcomes in infants born EPT. This finding may be associated with high interobserver variability in Apgar scoring, reduced vitality signs and poorer responses to resuscitation after birth among infants born EPT, and the association of more deleterious exposures in the neonatal intensive care unit or of socioeconomic factors with greater changes in outcomes during the first 5 years of life.

Developmental motor problems and health-related quality of life in 5-year-old children born extremely preterm: A European cohort study.

AIM: To measure the association between cerebral palsy (CP) and non-CP-related movement difficulties and health-related quality of life (HRQoL) among 5-year-old children born extremely preterm (<28 weeks gestational age). METHOD: We included 5-year-old children from a multi-country, population-based cohort of children born extremely preterm in 2011 to 2012 in 11 European countries (n = 1021). Children without CP were classified using the Movement Assessment Battery for Children, Second Edition as having significant movement difficulties (≤5th centile of standardized norms) or being at risk of movement difficulties (6th-15th centile). Parents reported on a clinical CP diagnosis and HRQoL using the Pediatric Quality of Life Inventory. Associations were assessed using linear and quantile regressions. RESULTS: Compared to children without movement difficulties, children at risk of movement difficulties, with significant movement difficulties, and CP had lower adjusted HRQoL total scores (ß [95% confidence interval] = -5.0 [-7.7 to -2.3], -9.1 [-12.0 to -6.1], and - 26.1 [-31.0 to -21.2]). Quantile regression analyses showed similar decreases in HRQoL for all children with CP, whereas for children with non-CP-related movement difficulties, reductions in HRQoL were more pronounced at lower centiles. INTERPRETATION: CP and non-CP-related movement difficulties were associated with lower HRQoL, even for children with less severe difficulties. Heterogeneous associations for non-CP-related movement difficulties raise questions for research about mitigating and protective factors.

The impact of perinatal brain injury on retinal nerve fiber layer thickness and optic nerve head parameters of premature children.

PURPOSE: This study aims to evaluate the impact of birth weight (BW), gestational age (GA), retinopathy of prematurity (ROP), and perinatal brain injury (PBI) on optic nerve head (ONH) parameters and nerve fiber layer thickness (RNFLT) in preterm children. METHODS: ONH parameters and RNFLT were examined prospectively in 5-15-year-old preterm and full-term children with RTVue-100 OCT (Optovue, USA). The parameters of the two groups were compared and possible influences of BW, GA, ROP, and PBI analyzed in preterm children. RESULTS: In total, 51 full-term and 55 preterm children were included. The mean age was 9.98 ± 3.4 years in full-term and 10.0 ± 2.5 years in preterm children. The mean GA in preterm children was 29.6 ± 3.8 weeks with a BW of 1523 ± 732 g. RNFLT was significantly lower in preterm than in full-term children in all but temporal quadrants. Cup area, volume, cup/disc area ratio, and horizontal cup/disc ratio (CDR) were significantly larger and rim area significantly thinner in preterm children. GA was positively correlated with superior, nasal, and overall RNFLT and negatively correlated with cup area, volume, and horizontal CDR. ROP stage correlated negatively with superior and nasal RNFLT. PBI was the only significant predicting factor for RNFL thinning in all but temporal quadrant in multiple regression analysis. Preterm children with PBI had a significantly larger optic cup (CDR 0.70 ± 0.33 vs. 0.37 ± 0.27) and thinner optic rim. CONCLUSION: PBI correlated strongest with RNFL thinning, a thinner optic rim, and a larger optic cup in preterm children and should be evaluated in each patient to prevent incorrect diagnosis like glaucoma.

Maternal Wellbeing Five Years after a Very Preterm Delivery: Prevalence and Influencing Factors in a European Cohort.

(1) Background: Mothers of very preterm (VPT) infants may experience psychological symptoms compromising long-term emotional wellbeing. This study describes the emotional wellbeing of mothers of five-year-old children born VPT. We assess the association between sociodemographic, perinatal and neonatal characteristics, and the child's health and development at five years old and maternal emotional wellbeing. (2) Methods: Data are from the prospective European "Effective Perinatal Intensive Care in Europe" (EPICE) and subsequent "Screening for Health In very Preterm infantS in Europe" (SHIPS) projects including births <32 weeks' gestational age in 11 countries in 2011/12. Data were abstracted from obstetric and neonatal records. At five years old, 2605 mothers answered a parental questionnaire including the Mental Health Inventory-5 (MHI-5). Associations between sociodemographic and health characteristics and the mother's MHI-5 score were investigated using multilevel multivariate linear regression analysis with the country modelled as a random effect and inverse probability weighting to correct for attrition bias. (3) Results: The mean MHI-5 score was 71.3 (SD 16.7) out of 100 (highest emotional wellbeing) with a variation among countries from 63.5 (SD 16.8; Poland) to 82.3 (SD 15.8; the Netherlands). MHI-5 scores were significantly lower for mothers whose child had a severe health problem, developmental, or speech delay, for multiparous and single mothers, and when at least one of the parents was unemployed. (4) Conclusions: The emotional wellbeing of mothers of VPT infants differs between European countries. Identifying sociodemographic characteristics and child's health and developmental conditions that affect maternal emotional wellbeing may help to identify groups of mothers who need special assistance to cope with consequences of the delivery of a VPT child.

NEO-SPEAK: A conceptual framework that underpins breaking bad news in neonatology.

Objective: Breaking bad news in neonatology is a frequent and difficult challenge. Although there are guidelines for communicating with parents in pediatrics and neonatology, the specific framework for breaking bad news in neonatology has not been studied in more detail. Therefore, we aimed to identify determinants that are important for successful managing breaking bad news in neonatology from professionals' perspective and to develop a conceptual framework that underpins this challenging task. Methods: We conducted seventeen semi-structured interviews with senior neonatologists of six perinatal centers of the highest level of care in Germany. The transcripts were analyzed according to Mayring's method of qualitative content analysis using inductive and deductive coding. Results: Eight determinants of breaking bad news in neonatology could be identified from the interviews. From these, we developed the conceptual framework NEO-SPEAK. The first three determinants, Neonatal prognostic uncertainty, Encounter in (triangular-)partnerships, Organization and teamwork (NEO) are directly related to the specific care situation in neonatology, whereas the others, Situational stress, Processuality, Emotional burden, Attention to individuality, Knowledge and experience, play a role for difficult conversations in general, but are subject to special modifications in neonatology (SPEAK). In addition, the results show that the context in neonatology as well as reciprocal effects on the team and the individual level of the physicians are important influencing factors in breaking bad news. Conclusion: On the one hand, the constitutional framework NEO-SPEAK shows which special aspects play a role in neonatology for the delivery of bad news, and on the other hand, it can help to identify and consider these aspects in clinical routine and training. Considering or reinforcing each NEO-SPEAK element when planning or delivering bad news may guide healthcare professionals through communication with parents of critically ill or premature newborns and support the resilience of the caring team.

Systemic Steroids in Preventing Bronchopulmonary Dysplasia (BPD): Neurodevelopmental Outcome According to the Risk of BPD in the EPICE Cohort.

BACKGROUND: Postnatal steroids (PNS) have been used to prevent bronchopulmonary dysplasia (BPD) in preterm infants but have potential adverse effects on neurodevelopment. These effects might be modulated by their risk of BPD. We aimed to compare patients' neurodevelopment with PNS treatment according to their risk of BPD in a European cohort. METHODS: We developed a prediction model for BPD to classify infants born between 24 + 0 and 29 + 6 weeks of gestation in three groups and compared patients' neurological outcome at two years of corrected age using the propensity score (PS) method. RESULTS: Of 3662 neonates included in the analysis, 901 (24.6%) were diagnosed with BPD. Our prediction model for BPD had an area under the ROC curve of 0.82. In the group with the highest risk of developing BPD, PNS were associated with an increased risk of gross motor impairment: OR of 1.95 after IPTW adjustment (95% CI 1.18 to 3.24, p = 0.010). This difference existed regardless of the type of steroid used. However, there was an increased risk of cognitive anomalies for patients treated with dexa/betamethasone that was no longer observed with hydrocortisone. CONCLUSIONS: This study suggests that PNS might be associated with an increased risk of gross motor impairment regardless of the group risk for BPD. Further randomised controlled trials exploring the use of PNS to prevent BPD should include a risk-based evaluation of neurodevelopmental outcomes. This observation still needs to be confirmed in a randomised controlled trial.

Mode of Delivery and Incidence of Bronchopulmonary Dysplasia: Results from the Population-Based EPICE Cohort.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) represents a tremendous disease burden following preterm birth. The strong association between compromised gas exchange after birth and BPD demands particular focus on the perinatal period. The mode of delivery can impact on lung fluid clearance and microbial colonization, but its impact on BPD and potential trade-off effects between death and BPD are not established. METHODS: A total of 7,435 live births (24+0 to 31+6 weeks postmenstrual age) in 19 regions of 11 European countries were included. Principal outcomes were death and BPD at 36 weeks. We estimated unadjusted and adjusted associations with mode of delivery using multilevel logistic regression to account for clustering within units and regions. Sensitivity analyses examined effects, taking into consideration regional variations in C-section rates. RESULTS: Compared to vaginal delivery, delivery by C-section was not associated with the incidence of BPD (OR 0.92, 95% CI: 0.68-1.25) or the composite outcome of death or BPD (OR 0.94, 95% CI: 0.74-1.19) after adjustment for perinatal and neonatal risk factors in the total cohort and in pregnancies for whom a vaginal delivery could be considered. Sensitivity analyses among singletons, infants in cephalic presentation, and infants of ≥26+0 weeks of gestation did not alter the results for BPD, severe BPD, and death or BPD, even in regions with a high C-section rate. CONCLUSIONS: In our population-based cohort study, the mode of delivery was not associated with the incidence of BPD. The intention to reduce BPD does not justify a C-section in pregnancies where a vaginal delivery can be considered.

International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn.

Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.

Maternal education and cognitive development in 15 European very-preterm birth cohorts from the RECAP Preterm platform.

BACKGROUND: Studies are sparse and inconclusive about the association between maternal education and cognitive development among children born very preterm (VPT). Although this association is well established in the general population, questions remain about its magnitude among children born VPT whose risks of medical and developmental complications are high. We investigated the association of maternal education with cognitive outcomes in European VPT birth cohorts. METHODS: We used harmonized aggregated data from 15 population-based cohorts of children born at <32 weeks of gestational age (GA) or <1500 g from 1985 to 2013 in 13 countries with information on maternal education and assessments of general development at 2-3 years and/or intelligence quotients between 4 and 15 years. Term-born controls (≥37 weeks of GA) were available in eight cohorts. Maternal education was classified as: low (primary/lower secondary); medium (upper secondary/short tertiary); high (bachelor's/higher). Pooled standardized mean differences (SMDs) in cognitive scores were estimated (reference: high educational level) for children assessed at ages 2-3, 4-7 and 8-15 years. RESULTS: The study included 10 145 VPT children from 12 cohorts at 2-3 years, 8829 from 12 cohorts at 4-7 years and 1865 children from 6 cohorts at 8-15 years. Children whose mothers had low, compared with high, educational attainment scored lower on cognitive measures [pooled unadjusted SMDs: 2-3 years = -0.32 (95% confidence intervals: -0.43 to -0.21); 4-7 years = -0.57 (-0.67; -0.47); 8-15 years = -0.54 (-0.72; -0.37)]. Analyses by GA subgroups (<27 vs ≥27 weeks) in children without severe neonatal morbidity and term controls yielded similar results. CONCLUSIONS: Across diverse settings and regardless of the degree of prematurity, low maternal education was associated with lower cognition.

High Healthcare Use at Age 5 Years in a European Cohort of Children Born Very Preterm.

OBJECTIVES: To describe parent-reported healthcare service use at age 5 years in children born very preterm and investigate whether perinatal and social factors and the use of very preterm follow-up services are associated with high service use. STUDY DESIGN: We used data from an area-based cohort of births at <32 weeks of gestation from 11 European countries, collected from birth records and parental questionnaires at 5 years of age. Using the published literature, we defined high use of outpatient/inpatient care (≥4 sick visits to general practitioners, pediatricians, or nurses, ≥3 emergency room visits, or ≥1 overnight hospitalization) and specialist care (≥2 different specialists or ≥3 visits). We also categorized countries as having either a high or a low rate of children using very preterm follow-up services at age 5 years. RESULTS: Overall, 43% of children had high outpatient/inpatient care use and 48% had high specialist care use during the previous year. Perinatal factors were associated with high outpatient/inpatient and specialist care use, with a more significant association with specialist services. Associations with intermediate parental educational level and unemployment were stronger for outpatient/inpatient services. Living in a country with higher rates of very preterm follow-up service use was associated with lower use of outpatient/inpatient services. CONCLUSIONS: Children born very preterm had high healthcare service use at age 5 years, with different patterns for outpatient/inpatient and specialist care by perinatal and social factors. Longer follow-up of children born very preterm may improve care coordination and help avoid undesirable health service use.