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Aim To (1) determine the proportion of 5‐year‐old children born extremely preterm (EPT) with movement difficulties including cerebral palsy (CP) and the proportion of these children receiving motor‐related health care (MRHC), and (2) describe factors associated with receiving MRHC. Method Children born before 28 weeks’ gestation in 2011 to 2012 in 11 European countries were assessed with the Movement Assessment Battery for Children, Second Edition (MABC‐2) at 5 years of age. Information on family characteristics, child health including CP diagnosis, and health care use were collected using parent‐report questionnaires. MRHC was defined as visits in the previous year with health care providers (physical and occupational therapists) specialized in assessing/treating motor problems. We analysed receipt of MRHC and associated factors among children at risk of movement difficulties (MABC‐2 score 6th–15th centiles), with significant movement difficulties (SMD; ≤5th centile) or with CP. Results Of 807 children assessed at 5 years 7 months (SD 4 months; 4 years 7 months–7 years 1 month), 412 were males (51.1%), 170 (21.1%) were at risk of movement difficulties, 201 (24.9%) had SMD, and 92 (11.4%) had CP. Those who received MRHC comprised 89.1% of children with CP, 42.8% with SMD, and 25.9% at risk of movement difficulties. MRHC for children with SMD varied from 23.3% to 66.7% between countries. Children were more likely to receive MRHC if they had other developmental problems or socioemotional, conduct, or attention difficulties. Interpretation Efforts are needed to increase MRHC for 5‐year‐old children born EPT with movement difficulties. What this paper adds Children born extremely preterm without cerebral palsy frequently experienced motor difficulties. Most of these children were not receiving motor‐related health care (MRHC). Large geographical differences throughout Europe were observed in receipt of MRHC. Socioemotional problems were related to MRHC use.

Purpose: The primary endpoint results from the comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity (CARE-ROP) core study identified ranibizumab as an effective treatment to control acute retinopathy of prematurity (ROP). This study reports the 1-and 2-year follow-up data focusing on long-term functional outcomes and safety. Methods:The CARE-ROP trial compared 0.12 mg versus 0.20 mg ranibizumab in 20 infants with ROP in a multicentric, prospective, randomized, double-blind, controlled study design. Sixteen patients entered the follow-up period. An ophthalmologic assessment at one year postbaseline was acquired from all 16 patients and a neurodevelopmental assessment at two years postbaseline was acquired from 15 patients.Results: Fifteen of 16 infants were able to fixate and follow moving objects at one year postbaseline treatment. One child progressed to stage 5 ROP bilaterally between the end of the core study and the 1-year follow-up (first seen at PMA 75 weeks). Mean spherical equivalents were À1.9 diopters (D) and À0.75 D in the 0.12 mg and the 0.20 mg treatment arms. Strabismus was present in seven and nystagmus in five out of 16 infants. Mental development scores were within normal limits in six out of ten patients with available data. No statistically significant difference was observed between the two treatment arms. Conclusion:Neurodevelopmental and functional ocular outcomes 1 and 2 years after treatment with ranibizumab are reassuring regarding long-term safety. Late reactivation of ROP, however, represents a challenge during the follow-up phase and it is of utmost importance that regular follow-ups are maintained.

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Aim Among children who receive hospital care, preterm infants are Europe's largest group, whose numbers are continually increasing. Currently, no pan‐European standards of care for preterm or critically ill infants are available, except for a few specific topics, and practices vary widely in different regions. Methods The European Foundation for the Care of Newborn Infants (EFCNI) has initiated a transdisciplinary collaboration project to provide agreed standards for high‐quality perinatal and neonatal care, whose implementation will ensure fairer and more equitable care across Europe. This will improve care for these vulnerable infants and their families, ameliorate the long‐term conditions found in preterm and critically ill infants and enhance the quality of family life of affected families. More than 220 experts—healthcare professionals, patient representatives and other relevant stakeholders—have come together for the first time to develop a broad reference guidance in neonatology and associated fields. Results Ninety‐six standards on 11 overarching topic areas were developed and endorsed. Conclusion This reference framework serves as a basis for the development of binding national standards for high‐quality care. A robust translation and implementation strategy is facilitated, with the goal of improved health outcomes following preterm birth all around Europe.

Purpose This study aims to (1) describe the health-related quality of life (HRQoL) outcomes experienced by children born very preterm (28–31 weeks’ gestation) and extremely preterm (< 28 weeks’ gestation) at five years of age and (2) explore the mediation effects of bronchopulmonary dysplasia (BPD) and severe non-respiratory neonatal morbidity on those outcomes. Methods This investigation was based on data for 3687 children born at < 32 weeks’ gestation that contributed to the EPICE and SHIPS studies conducted in 19 regions across 11 European countries. Descriptive statistics and multi-level ordinary linear squares (OLS) regression were used to explore the association between perinatal and sociodemographic characteristics and PedsQL™ GCS scores. A mediation analysis that applied generalised structural equation modelling explored the association between potential mediators and PedsQL™ GCS scores. Results The multi-level OLS regression (fully adjusted model) revealed that birth at < 26 weeks’ gestation, BPD status and experience of severe non-respiratory morbidity were associated with mean decrements in the total PedsQL™ GCS score of 0.35, 3.71 and 5.87, respectively. The mediation analysis revealed that the indirect effects of BPD and severe non-respiratory morbidity on the total PedsQL™ GCS score translated into decrements of 1.73 and 17.56, respectively, at < 26 weeks’ gestation; 0.99 and 10.95, respectively, at 26–27 weeks’ gestation; and 0.34 and 4.80, respectively, at 28–29 weeks’ gestation (referent: birth at 30–31 weeks’ gestation). Conclusion The findings suggest that HRQoL is particularly impaired by extremely preterm birth and the concomitant complications of preterm birth such as BPD and severe non-respiratory morbidity.

ImportanceOne of the biggest challenges when using anti–vascular endothelial growth factor (VEGF) agents to treat retinopathy of prematurity (ROP) is the need to perform long-term follow-up examinations to identify eyes at risk of ROP reactivation requiring retreatment.ObjectiveTo evaluate whether an artificial intelligence (AI)–based vascular severity score (VSS) can be used to analyze ROP regression and reactivation after anti-VEGF treatment and potentially identify eyes at risk of ROP reactivation requiring retreatment.Design, Setting, and ParticipantsThis prognostic study was a secondary analysis of posterior pole fundus images collected during the multicenter, double-blind, investigator-initiated Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP) randomized clinical trial, which compared 2 different doses of ranibizumab (0.12 mg vs 0.20 mg) for the treatment of ROP. The CARE-ROP trial screened and enrolled infants between September 5, 2014, and July 14, 2016. A total of 1046 wide-angle fundus images obtained from 19 infants at predefined study time points were analyzed. The analyses of VSS were performed between January 20, 2021, and November 18, 2022.InterventionsAn AI-based algorithm assigned a VSS between 1 (normal) and 9 (most severe) to fundus images.Main Outcomes and MeasuresAnalysis of VSS in infants with ROP over time and VSS comparisons between the 2 treatment groups (0.12 mg vs 0.20 mg of ranibizumab) and between infants who did and did not receive retreatment for ROP reactivation.ResultsAmong 19 infants with ROP in the CARE-ROP randomized clinical trial, the median (range) postmenstrual age at first treatment was 36.4 (34.7-39.7) weeks; 10 infants (52.6%) were male, and 18 (94.7%) were White. The mean (SD) VSS was 6.7 (1.9) at baseline and significantly decreased to 2.7 (1.9) at week 1 (P &amp;lt; .001) and 2.9 (1.3) at week 4 (P &amp;lt; .001). The mean (SD) VSS of infants with ROP reactivation requiring retreatment was 6.5 (1.9) at the time of retreatment, which was significantly higher than the VSS at week 4 (P &amp;lt; .001). No significant difference was found in VSS between the 2 treatment groups, but the change in VSS between baseline and week 1 was higher for infants who later required retreatment (mean [SD], 7.8 [1.3] at baseline vs 1.7 [0.7] at week 1) vs infants who did not (mean [SD], 6.4 [1.9] at baseline vs 3.0 [2.0] at week 1). In eyes requiring retreatment, higher baseline VSS was correlated with earlier time of retreatment (Pearson r = −0.9997; P &amp;lt; .001).Conclusions and RelevanceIn this study, VSS decreased after ranibizumab treatment, consistent with clinical disease regression. In cases of ROP reactivation requiring retreatment, VSS increased again to values comparable with baseline values. In addition, a greater change in VSS during the first week after initial treatment was found to be associated with a higher risk of later ROP reactivation, and high baseline VSS was correlated with earlier retreatment. These findings may have implications for monitoring ROP regression and reactivation after anti-VEGF treatment.

Purpose Postapproval reports of intraocular inflammation (IOI) and occlusive retinal vasculitis following intravitreal brolucizumab are accumulating. A role of anti‐drug antibodies (ADAs) to brolucizumab is under current scientific discussion. The purpose of the present study was to measure brolucizumab ADAs in a cross‐sectional ophthalmic patient population and to compare the occurrence of brolucizumab ADAs with that of ranibizumab ADAs. Methods One hundred and ninety‐two serum samples and 54 vitreous samples were collected from patients with a range of eye diseases including neovascular age‐related macular degeneration (AMD), diabetic retinopathy, retinal vein occlusion, cataract, glaucoma, dry eye disease, macular hole, epiretinal membranes and intraocular lens (IOL) dislocation. Serum and vitreous samples were analysed for immune globuline (Ig) G ADAs to brolucizumab and ranibizumab using indirect enzyme‐linked immunosorbent assay (ELISA). Optical Density (OD) was read at 450 nm (wavelength correction at 550 nm) for ADA level measurements. Results Presence of brolucizumab ADAs was observed in patients with and without prior brolucizumab exposure. Both the frequency of notable ADA signals (OD > 0.1) and the mean ADA signal in serum samples were higher for brolucizumab than for ranibizumab. Two patients who experienced severe IOI and occlusive retinal vasculitis following intravitreal brolucizumab had high brolucizumab ADA serum levels. In one of these two patients, high brolucizumab ADA levels were also found in vitreous. Another patient developed moderate IOI without retinal vasculitis in the presence of low brolucizumab ADA serum levels. Overall, notable brolucizumab ADA levels were less frequent in vitreous than in the corresponding serum samples but with a tendency for higher prevalence in vitreous from patients with diabetic retinopathy. Conclusion Brolucizumab ADAs occur with significant prevalence in a typical ophthalmic patient population and may represent a risk factor for IOI and occlusive retinal vasculitis following brolucizumab.