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.

IMPORTANCEThe inclusion of less invasive surfactant administration (LISA) in the care of preterm infants has been found to be beneficial for respiratory outcomes. Recently, the OPTIMIST trial found higher mortality rates in the subgroup of infants born at 25 to 26 weeks' gestational age (GA) who received surfactant treatment while spontaneously breathing. OBJECTIVETo analyze outcomes among LISA-exposed, highly vulnerable babies born at less than 27 weeks' GA within the large-scale observational cohort of the German Neonatal Network. DESIGN, SETTING, AND PARTICIPANTSIn this cohort study of data from 68 tertiary level neonatal intensive care units in Germany of infants born between 22 weeks 0 days to 26 weeks 6 days of gestation between April 1, 2009, and December 31, 2020, short-term outcomes among infants receiving LISA vs infants not receiving LISA were compared. EXPOSURE Use of LISA within the first 72 hours of life. MAIN OUTCOMES AND MEASURESThe main outcomes were rates of LISA use, use of mechanical ventilation within the first 72 hours (considered failure of LISA), and association of LISA with outcomes, including death from all causes, bronchopulmonary dysplasia (BPD), death and BPD combined, pneumothorax, retinopathy of prematurity, intracerebral hemorrhage, and periventricular leukomalacia. To address potential confounding factors, multivariate logistic regression models were used. RESULTSA total of 6542 infants (3030 [46.3%] female and 3512 [53.7%] male; mean [SD] GA, 25.3(1.1) weeks; mean [SD] birth weight, 715 [180] g) were analyzed; 2534 infants (38.7%) received LISA, which was most frequently given quasi-prophylactically during delivery room management. Among the infants who received LISA, 1357 (53.6%) did not require mechanical ventilation in the first 72 hours compared with 331 infants (8.3%) of 4008 who did not receive LISA. In a multivariate logistic regression model that adjusted for GA, small-for-GA status, sex, multiple birth, inborn status, antenatal steroid use, and maximum fraction of inspired oxygen in the first 12 hours of life, LISA was associated with reduced risks of all-cause death (odds ratio [OR], 0.74; 95% CI, 0.61-0.90; P = .002), BPD (OR, 0.69; 95% CI, 0.62-0.78; P < .001), and BPD or death (OR, 0.64; 95% CI, 0.57-0.72; P < .001) compared with infants without LISA exposure. CONCLUSIONS AND RELEVANCEThe results of this long-term multicenter cohort study suggest that LISA may be associated with reduced risks of adverse outcomes in extremely preterm infants.

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.

Background: To determine whether the secretor gene fucosyltransferase (FUT)2 polymorphism G428A is predictive for adverse outcomes in a large cohort of very-low-birth weight (VLBW) infants. Methods: We prospectively enrolled 2,406 VLBW infants from the population-based multicenter cohort of the German Neonatal network cohort (2009)(2010)(2011). The secretor genotype (rs601338) was assessed from DNA samples extracted from buccal swabs. Primary study outcomes were clinical sepsis, blood-culture confirmed sepsis, intracerebral hemorrhage (ICH), necrotizing enterocolitis (NEC) or focal intestinal perforation requiring surgery, and death. results: Based on the assumption of a recessive genetic model, AA individuals had a higher incidence of ICH (AA: 19.0% vs. GG/AG: 14.9%, P = 0.04) which was not significant in the additive genetic model (multivariable logistic regression analysis; allele carriers: 365 cases, 1,685 controls; OR: 1.2; 95% CI: 0.99-1.4; P = 0.06). Other outcomes were not influenced by FUT2 genotype in either genetic model. conclusion: This large-scale multicenter study did not confirm previously reported associations between FUT2 genotype and adverse outcomes in preterm infants. t he secretor status, i.e., the ability to secrete ABH histoblood group antigens into body fluids is determined by the enzyme fucosyltransferase 2 which is encoded by the FUT2 gene. About 80% of the Caucasian populations are secretors (either homozygous SeSe or heterozygous Sese) while the remaining 20% carry the homozygous 428G→A nonsense mutation in the FUT2 gene and are nonsecretors (sese). Several in vivo studies have revealed the clinical significance of this polymorphism and the secretor status in terms of susceptibility to infection and association with immunologically mediated diseases (1-6). Thorven et al. (1) were able to demonstrate that secretor-negative individuals are resistant to Norovirus infections possibly due to binding of Norovirus to secreted ABH histo-blood group antigens as indispensable condition for infection. Another study noted that secretor individuals are overrepresented in a cohort of patients with viral infections of the respiratory tract (2). So far the only investigation involving preterm infants found a strong association between secretor status and severe outcome (i.e., death, necrotizing enterocolitis (NEC), Gram-negative sepsis) in a cohort of 410 premature infants (6).The aim of this study was to determine possible associations between the FUT2 genotype and short-term as well as longterm outcomes in a large cohort of 2,406 preterm infants with a birth weight < 1,500 g (very-low-birth weight (VLBW)) from the German Neonatal Network. RESULTS Genotype FrequenciesIn the German Neonatal Network cohort including infants born between 2009-2011, n = 2,566 infants were enrolled (64.8% of eligible infants; early death occurred in 21% of nonenrolled infants). As ethnic differences for FUT 2 genotype distribution have been previously noted, we decided to exclude infants with Asian (n = 48), African (n...

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