Articles published on First Month Of Life
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- New
- Research Article
- 10.1016/j.earlhumdev.2025.106477
- Mar 1, 2026
- Early human development
- Sophie Dixon + 8 more
The motor optimality of infants who have had Meningitis in the first months of life: A retrospective study.
- New
- Research Article
- 10.1016/j.prevetmed.2025.106781
- Mar 1, 2026
- Preventive veterinary medicine
- José M Hernández-Agudelo + 6 more
A bayesian analysis of phage-based qPCR and liquid culture for the early detection of Mycobacterium avium subsp. paratuberculosis in young dairy calves.
- New
- Research Article
- 10.1186/s41043-026-01270-5
- Feb 21, 2026
- Journal of health, population, and nutrition
- Ruhul Amin + 5 more
Respiratory syncytial virus (RSV) remains a leading cause of infant morbidity and mortality, with the highest burden concentrated in low- and middle-income countries (LMICs). Existing preventive options, including long-acting monoclonal antibodies, can be constrained by cost, logistics, and access, leaving many high-risk infants unprotected. This article is a structured narrative review summarizing clinical efficacy, immunological mechanisms, safety and public health implications of maternal RSV immunization for preventing infant RSV lower respiratory tract infection (LRTI), with an explicit implementation focus for LMICs. Evidence was identified through targeted searches of major biomedical databases and prioritized by clinical relevance and policy importance, including phase III efficacy trials, regulatory and technical documents, post-authorization safety signals, and modelling studies evaluating potential impact in LMICs. Across the evidence base, maternal vaccination induces robust RSV-neutralizing IgG responses and efficient transplacental antibody transfer, providing passive protection during the first months of life when RSV risk is highest. In phase III data, maternal RSV vaccination demonstrated high efficacy against severe medically attended RSV LRTI in early infancy (e.g., up to 81.8% within the first 90 days for a licensed maternal RSV vaccine). Modelling studies project substantial global reductions in hospitalizations and deaths, although real-world effectiveness in LMICs will depend on antenatal care coverage, timing feasibility, seasonality, and equity of delivery. Safety findings were generally favorable; nonetheless, continued post-licensure monitoring,particularly for pregnancy and birth outcomes such as preterm birth,remains essential. Maternal RSV immunization is a scalable strategy that can leverage existing antenatal platforms and, if equitably implemented, could meaningfully reduce infant RSV morbidity and mortality, especially in LMIC settings.
- New
- Research Article
- 10.1038/s41390-026-04778-y
- Feb 17, 2026
- Pediatric research
- Aranka J Van Wesemael + 17 more
After birth, antibiotics are frequently administered to preterm infants for suspected early onset sepsis (EOS). Early empiric antibiotic exposure (EEAE) may disrupt the gut microbiota of preterm infants. This study investigates the association between EEAE duration and gut microbiota dynamics in the first month of life in very preterm infants. A selected cohort of 127 very preterm infants (<30 weeks gestation) without antibiotic exposure after the first week of life, was stratified into 3 EEAE groups: non (n = 36), short (48-96 h; n = 56), and long-exposed (96-192 h; n = 35). Microbiota composition was analyzed by 16S rRNA gene amplicon sequencing of fecal samples collected at week 1-4. EEAE duration was associated with increased alpha-diversity over time. Veillonella and Enterococcus were significantly lower in EEAE groups compared to non-exposed infants. Four microbial community types (CTs) were identified independent of antibiotic duration. Both EEAE groups had a higher prevalence of the Staphylococcus CT. Both short and long EEAE are associated with changes in the preterm gut microbiota, impacting alpha-diversity, taxonomic composition, and one community type's prevalence in the first month of life. These findings underscore the impact of antibiotic initiation for suspected EOS on the preterm gut microbiota. This multicenter cohort study investigates the impact of early empiric antibiotic exposure in very preterm infants on the gut microbiota during the first month of life. It includes a unique control group of infants without any antibiotic exposure. It shows both short and long early empiric antibiotic exposure affects the gut microbiota diversity, composition, and community type during the first month of life. Efforts aimed at reducing the initiation of early empirical antibiotic treatment in very preterm infants with suspected early-onset sepsis may help mitigate disruptions to the developing gut microbiota.
- New
- Research Article
- 10.1515/cclm-2025-1440
- Feb 17, 2026
- Clinical chemistry and laboratory medicine
- Robert Zeidler + 10 more
The adrenal glands are the main source of 11-oxygenated androgens (11-OAs), including the potent11-ketotestosterone (11-KT) and the weaker metabolites 11β-hydroxyandrostenedione (11-OHA4), 11β-hydroxytestosterone (11-OHT) and 11-ketoandrostenedione (11-KA4). Due to their adrenal origin, 11-OAs allow the differentiation of adrenal and extra-adrenal-produced androgens. However, their clinical use is limited due to the lack of robust age- and sex-specific reference intervals (RIs). To establish RIs from infancy throughout childhood and adulthood, we performed simultaneous quantification of 11-OHA4, 11-OHT, 11-KA4, 11-KT, and clinically relevant steroid hormones via LC-MS/MS. We analyzed 3,796 serum samples from 2,505 healthy individuals, aged 0.25-80 years, encompassing minipuberty and pubertal stages. 11-OA serum levels increase from infancy throughout childhood and adulthood, with the most pronounced increase during puberty. Significant sex differences were observed, and age-, sex-, and puberty-dependent RIs were established. In contrast to testosterone, 11-OAs exhibited a comparable pattern during the first year of life in both sexes. At 3 and 6 months of age-when testosterone levels were 100- and 10-fold higher, respectively, in males than in females-no correlation was observed between testosterone and the adrenal-derived androgens (11-OAs, A4, and DHEAS) inmales. Established age-, sex-, and puberty-dependent RIs support the clinical interpretation of 11-OA measurements in disorders characterized by androgen excess. The differences in the regulation of classical androgens and 11-OAs during minipuberty suggest that the transient increase in androgens during the first months of life is most likely due to activation of the hypothalamic-pituitary-gonadalaxis.
- New
- Research Article
- 10.1080/00324728.2025.2608593
- Feb 17, 2026
- Population Studies
- Alessandra Minello + 1 more
In the past, the choice of children’s names was closely linked to life trajectories. This paper investigates the connection between children’s names and child mortality during the demographic transition. Analysing data from the Veneto region (Northern Italy) and the Venetian parish of San Marco between 1816 and 1869, we find that traditional names are associated with higher neonatal mortality, particularly among girls. In contrast, children with unconventional names—those not named after grandparents or godparents or given the most frequent traditional names—face a lower risk of dying within the first month of life. Our findings underscore the importance of names in historical demography as predictors of demographic trajectories. Moreover, they suggest that naming practices may mirror varying levels of parental attention or a shift towards more modern concepts of childcare.
- New
- Research Article
- 10.52419/issn2782-6252.2025.4.233
- Feb 11, 2026
- Legal regulation in veterinary medicine
- M V Shchipakin + 1 more
The study of the vascular system, in particular the arterial bed, is a fundamental basis for the development of veterinary medicine, especially in such fields as surgery, orthopedics and traumatology. The shin area in breeding farm animals, including goats, is subject to high functional loads and the risk of injury, which necessitates a detailed knowledge of its blood supply. The purpose of the study is to study and analyze the topography, branching and age dynamics of the shin arteries in goats using the example of the Anglo-Nubian breed, as well as to assess the practical significance of research in the work of a veterinary surgeon. The study was conducted at the Department of Animal Anatomy of the St. Petersburg State University of Veterinary Medicine. The study was conducted in three age groups: newborn baby goats; young animals 5-6 months old; adult animals. To achieve this goal, traditional morphological research methods were used, namely: fine anatomical dissection, photographing, and vasorentgenography with morphometry in the RadiAnt program. According to the results of the study, it was found that the arterial bed of the shin in Anglo-Nubian goats is a complexly organized system with certain age-related patterns of development. The popliteal artery serves as the main source of blood supply, giving rise to the cranial and caudal tibial arteries, which, in turn, provide vascularization of muscle groups, bones and joints. The safin artery plays not only an auxiliary, but also a collateral role. Morphometric data convincingly demonstrate intensive vascular growth in the first months of life, which must be taken into account when developing surgical techniques for young animals.
- New
- Research Article
- 10.52419/issn2782-6252.2025.4.219
- Feb 11, 2026
- Legal regulation in veterinary medicine
- A I Polyanskaya + 1 more
This work is devoted to the analysis of the anatomical course, branching and age dynamics of the main arteries supplying the stomach of pigs in order to identify patterns of their growth and assess their functional significance. Knowledge of the anatomy of the vascular bed, in particular the arterial system, is a fundamental basis for the development of both veterinary medicine and animal husbandry. The aim of the study was to study the topography of the hepatic artery as a source of blood supply to the stomach in Yorkshire pigs, as well as to analyze age dynamics. The study was conducted at the Department of Animal Anatomy of the Federal State Budgetary Educational Institution of Higher Education in St. Petersburg in three age groups: one-day-old newborns; 10-14-day-old; 28-30-day-old pigs. To achieve this goal, traditional morphological research methods were used, namely: fine anatomical dissection, photographing, vasorentgenography with morphometry in the RadiAnt program. The analysis demonstrates that the arterial system of the stomach of pigs is a complex but logically organized structure originating from the hepatic artery. Its development in early postnatal ontogenesis is intensive and proactive, which is directly related to the functional load on the organ and the overall growth rate of the body. The most significant increase in the diameter of the main vessels (the right gastric and right gastro-omentum arteries) is observed by the end of the first month of life, as the digestive system prepares for the transition to an adult type of diet. Deep knowledge of anatomical and morphometric features is an indispensable tool for improving the efficiency of veterinary care, optimizing maintenance technologies and, ultimately, ensuring the health and productivity of pigs.
- New
- Research Article
- 10.52419/issn2782-6252.2025.4.45
- Feb 11, 2026
- Legal regulation in veterinary medicine
- R M Vasiliev
In the current political and economic conditions, ensuring the country's food security comes to the fore. Animal husbandry is an important component of food security, as a source of supply of diverse and highquality food products to the population. The effective development of this industry is impossible without the introduction of intensive technologies, the element of which is to maintain a high level of productivity and animal health. To achieve these goals, it is necessary to steadily reduce the incidence of infectious and noninfectious diseases in animals by improving their diagnostic and treatment methods. One of the diseases characterized by the difficulty of timely diagnosis is genital mycoplasmosis of cattle, the study of which is an urgent task. The article examines the effect of some methods of therapy of dry cows with genital mycoplasmosis on the degree of infection and vital characteristics of the calves obtained from them. During the experiment, it was found that the use of the antibiotic traksovet for the treatment of cows, as well as its combination with the immunomodulator thymalin, leads to a marked decrease in mycoplasma infection of their offspring. In the early postnatal period, the offspring of cows who received treatment, compared with their peers from mothers who were not treated, showed a lower lag in body weight gain in the first month of life, as well as significantly reduced rates of diarrhea and bronchopneumonia, with a particularly positive effect in the group where complex therapy was used.
- New
- Research Article
- 10.1136/archdischild-2025-329684
- Feb 9, 2026
- Archives of disease in childhood. Fetal and neonatal edition
- Tommaso Biagioni + 8 more
To assess the predictive accuracy of early neurophysiological and neuroimaging biomarkers, alone and in combination, for adverse neurodevelopmental disorders in term-born infants with neonatal encephalopathy (NE). Systematic review and meta-analysis conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy guidelines. Eligible studies included infants born at term with NE who underwent amplitude-integrated EEG (aEEG) or EEG and MRI of the brain within the first month of life. Adverse outcomes, assessed at 18-36 months of age, were defined as cerebral palsy, postneonatal epilepsy, severe hearing or visual impairment, moderate-to-severe developmental delay, or death attributable to NE. Searches were conducted in MEDLINE, CINAHL, Embase and Web of Science from database inception to 10 June 2025; risk of bias of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C) tool. Sensitivity, specificity and diagnostic odds ratio (DOR) of abnormal aEEG background, EEG background, EEG seizures and MRI injury, individually and in combination, for predicting adverse outcomes, pooled using Bayesian bivariate random effects meta-analyses. 27 studies including 1843 infants were analysed. MRI injury was the individual predictor with higher DOR estimate (31.01, 95% CI 15.07 to 72.82), followed by abnormal EEG background (16.84, 95% CI 5.88 to 50.59), while abnormal aEEG background and EEG seizures performed less well (7.99, 95% CI 2.40 to 33.00; 4.46, 95% CI 1.86 to 11.42). Combining EEG background with MRI injury improved DOR (78.59, 95% CI 19.72 to 321.36) and specificity (93.8%, 95% CI 85.2% to 97.9%) compared with MRI alone. MRI is a strong individual predictor of adverse outcomes in NE. Combining it with early EEG improves prognostic accuracy and may better support clinical decision-making. CRD42024585816.
- Research Article
- 10.22239/2317-269x.02409
- Feb 6, 2026
- Vigilância Sanitária em Debate
- Mykelli De Andrade Santos Soares + 3 more
Introduction: Nutrition in the first months of life is crucial for child development, and breastfeeding is widely recommended by institutions such as the World Health Organization (WHO) and the Brazilian Ministry of Health. However, in situations where breastfeeding is not possible, infant formulas have emerged as an essential alternative. In this context, understanding the Brazilian regulatory framework for these formulas is fundamental to ensuring food safety and product quality. Objective: To describe how Brazilian legislation regulates the formulation, commercialization, microbiological quality, and use of infant formulas (IF) for infants, as well as to analyze the implications of this regulation for public health and the infant food market. Method: This is a narrative review study of the literature and national legislation regarding IF. Resolutions from the National Health Surveillance Agency (Anvisa), federal laws, and technical standards were consulted, in addition to scientific articles published between 2014 and 2024 in databases such as SciELO, LILACS, PubMed, and Google Scholar. The descriptors used were “infant formulas,” “nutritional composition,” and “Brazilian legislation.” Results: The analysis showed that Brazil has a robust set of regulatory instruments, including Law No. 11,265/2006 (NBCAL) and Resolutions RDC No. 43, 44, and 45/2011, which regulate the composition, labeling, and commercialization of IF, as well as RDC No. 429/2020, which defines rules for nutritional labeling. RDC No. 724/2022 is also noteworthy, as it establishes strict microbiological standards. Reviewed studies indicated that, although most IF partially comply with current legislation, nonconformities were mainly related to labeling and nutritional composition. Conclusion: The analyzed studies revealed at least one nonconformity with current legislation, highlighting the need for infant formula manufacturers to adapt their products to the relevant regulations and for health authorities to intensify inspections to ensure greater effectiveness in law enforcement, thus guaranteeing product quality and protecting infant health.
- Research Article
- 10.1016/j.tvjl.2026.106560
- Feb 1, 2026
- Veterinary journal (London, England : 1997)
- Barbara Błaszczyk + 4 more
Doppler parameters in the common carotid, temporal and vertebral arteries in Suffolk lambs in the first month of life.
- Research Article
- 10.1515/cclm-2025-0985
- Jan 29, 2026
- Clinical chemistry and laboratory medicine
- Yue-Qi Li + 3 more
High-sensitivity cardiac troponin T (hs-cTnT) is used in pediatric healthcare to diagnose and assess the prognosis of various cardiac diseases, such as acute myocarditis, congenital heart disease, dilated cardiomyopathy, and heart failure. However, the standardized age-related reference intervals, 99th percentile cut-offs, and clinical guidelines are currently unavailable, especially in newborns and infants, making interpreting this biomarker challenging. Residual serum samples were collected from 1,047 pediatric subjects with no cardiovascular disease, including 145 neonates and 902 infants. The concentrations of hs-cTnT were analyzed using Roche's Elecsys Troponin T hs assay. The age-related 99th percentile cut-offs with 90 % confidence intervals (CIs) of hs-cTnT were established. Subjects were divided into age subgroups as follows: newborns (0-30days, n=142), infants aged 1month (31-60days, n=223), 2months (61-90days, n=152), 3-4months (91-150days, n=211), 5-6months (151-210days, n=149), and 7months-1 year (211-365days, n=149). Serum hs-cTnT concentrations were highest during the first month of life and progressively declined in a year. The 99th percentile cut-offs of hs-cTnT concentration in each group were as follows: 114 (90 % CI: 114-114), 65.6 (63.7-66.1), 55.2 (54.4-55.2), 30.4 (29.1-30.9), 23.5 (22.1-23.5), 12.7 (12.4-12.7) ng/L. The 97.5th percentile cut-offs for each group were 109.4 (105.2-114), 62.5 (60.5-63.9), 52.3 (50.3-54.4), 29 (28.5-29.1), 20.5 (19.2-23.4), and 12 (12-12.1)ng/L. This study aimed to provide reliable pediatric reference values for hs-cTnT based on a population of well-child children. These reference intervals and 99th percentile cut-offs will inform clinical decisions in the pediatric cardiology setting.
- Research Article
- 10.1038/s41598-025-34344-1
- Jan 28, 2026
- Scientific reports
- Serap Özdemir + 3 more
Infantile colic is an important problem encountered during the first months of life. This study investigated the effect of infantile colic training provided to parents on the severity of neonatal infantile colic and the duration of crying. The research used a one-group pretest-posttest design. The study was conducted among the mothers and fathers of newborns who attended a Family Health Center between May and October 2024 and were diagnosed with infantile colic. A power analysis was conducted, and the sample consisted of 60 parents. Parents received infantile colic training in a single session, and its effectiveness was evaluated at two different times. Data were obtained via a questionnaire that included a sociodemographic form and the Infantile Colic Scale. The crying times of the newborns were recorded based on the information provided by the parents. Statistically significant differences in the Infantile Colic Scale scores were not found in mothers after the training; however, significant differences were observed in the first post-education assessment of fathers and between the parents' first and second assessments. The mean duration of infant crying after the training was found to have a high effect size. After the training, it was found that the severity of newborn infantile colic and the duration of crying decreased. This training is an effective intervention for neonatal infantile colic.
- Research Article
- 10.18203/2349-3291.ijcp20260088
- Jan 27, 2026
- International Journal of Contemporary Pediatrics
- Haniya P C
Background: Early initiation and exclusive breastfeeding are one of the most effective ways to ensure child’s survival, growth and development. Breast milk is the ideal food for infants which helps to protect against many common childhood illnesses and provides all the energy and nutrients that needed for the first months of life. However, only less than half of infants under 6 months old are exclusively breastfed. This study is aimed to assess the early initiation, knowledge and exclusive breastfeeding practices among postnatal mothers in the community of Perinthalmanna, North Kerala. Methods: A community based cross sectional study was conducted among 146 postnatal mothers with infants aged 0–6 months for a period of 3 months. Data were collected using a structured questionnaire covering socio-demographic details, early initiation of breastfeeding, exclusive breastfeeding and influencing factors. Descriptive analysis was performed using percentages and proportions. Results: Among 146 participants, 78% initiated breastfeeding within one hour of delivery, out of which 65% practiced exclusive breastfeeding at the time of study. The main reasons for delayed initiation were cesarean delivery and lack of guidance. Mothers with higher education and prior counseling practiced exclusive breastfeeding. Conclusions: Although breastfeeding initiation rates are satisfactory, exclusive breastfeeding practices remain suboptimal. Health care professionals should provide continuous breastfeeding education and postnatal counseling to mothers, especially first-time mothers which can improve early initiation and exclusive breastfeeding practices.
- Research Article
- 10.18203/2349-3291.ijcp20260114
- Jan 27, 2026
- International Journal of Contemporary Pediatrics
- Anjali Joshi + 1 more
Gilbert syndrome, a relatively common but less conspicuous condition, is characterized by intermittent episodes of mild to moderate unconjugated hyperbilirubinemia due to limited activity of the enzyme UGT1A1. It is usually benign and often remains unnoticed due to overlap with physiological jaundice. We report a case of term male neonate who developed four distinct episodes of severe, recurrent unconjugated hyperbilirubinemia within the first month of life, each requiring intensive phototherapy. Extensive evaluation excluded hemolysis, sepsis, endocrine dysfunction, and cholestatic liver disease as cause of jaundice. Given the atypical presentation with recurrent neonatal jaundice and no identifiable underlying cause, genetic testing was performed, which revealed compound heterozygosity for UGT1A1 variants (-3279T>G promoter polymorphism and 211G>A exon 1 mutation), confirming Gilbert syndrome. The infant responded promptly to phototherapy and had normal BERA and MRI brain with age-appropriate developmental milestones. This case highlights an atypically severe and recurrent neonatal presentation of Gilbert syndrome in the absence of known exacerbating factors and emphasizes the importance of genetic testing to distinguish Gilbert syndrome from Crigler-Najjar syndrome, guide management, and avoid unnecessary invasive interventions.
- Research Article
- 10.53126/mebxxixg023
- Jan 23, 2026
- Medico e Bambino Pagine elettroniche
- Umberto Laudante + 6 more
This study examines the role of early diagnosis in managing inborn errors of immunity, which are often characterised by early onset and high mortality. By analysing data from 15 patients with a positive family history, the research evaluated the utilization of pre-implantation and prenatal diagnostic tools. While prenatal diagnosis was performed in five cases, all families chose to continue the pregnancy. Early identification, whether prenatal or within the first month of life, enabled the immediate implementation of critical preventive measures, such as protective isolation, strict aseptic techniques and specific antimicrobial prophylaxis. The findings demonstrate that timely diagnosis and prompt prophylactic intervention are essential to reducing infection rates and improving the overall prognosis for infants with hereditary immune disorders.
- Research Article
- 10.1002/jpn3.70341
- Jan 15, 2026
- Journal of pediatric gastroenterology and nutrition
- Jacqueline Muts + 10 more
High protein intake during infancy has been linked to accelerated weight gain and increased obesity risk. This study aimed to examine the effects of a low-protein formula during the first 6 months of life on blood metabolic and hormonal markers during early childhood. Formula-fed infants (<45 days) were randomized to receive either a low-protein formula with modified amino acid composition (mLP; n = 90; 1.7 g protein/100 kcal) or a control formula (CTRL; n = 88; 2.1 g protein/100 kcal) until 6 months of age. Breastfed infants served as a reference group (n = 67). Blood samples were collected in cooperating subjects at 1, 2, and 6 years. We measured insulin-like growth factor-1 (IGF-1), IGF-binding proteins (BPs), leptin, glucose, and insulin, and calculated Homeostatic-Model-Assessment-of-Insulin-Resistance (HOMA-IR). Data were analyzed using linear mixed models and linear regression, adjusting for confounders. In addition, results were correlated to priorly published body composition measurement. Venous blood was collected from 87 (36%), 77 (31%), and 63 (26%) participants at ages 1, 2, and 6 years, respectively. No differences were found in metabolic markers between the formula groups or compared to the breastfed group at any time point. Furthermore, at 6 years of age, a positive correlation was found between some biomarkers (IGF-1, leptin, and HOMA-IR) and body composition measurements, but not all biomarkers showed such an association. In this relatively small study, providing a modified, low-protein infant formula during the first months of life did not affect hormonal and metabolic markers during early childhood.
- Research Article
1
- 10.1097/mco.0000000000001206
- Jan 9, 2026
- Current opinion in clinical nutrition and metabolic care
- Anne H Lafeber + 3 more
While moderate and late preterm infants (MLPTI, gestational age 32 0/7-36 6/7 weeks) represent the largest group of preterm infants worldwide, studies on nutritional needs remain scarce. This review evaluated the latest evidence on nutritional strategies for MLPTI and their effect on growth and body composition. For the first time, specific recommended nutritional intakes were defined by a group of experts, resulting in a recommended protein intake of 3.1-3.5 g/kg/day and a recommended energy intake of 127-130 kcal/kg/day. However, most MLPTI fail to meet these targets in the first week of life. Higher early protein and energy intakes were associated with improved weight gain, head growth, and reduced extra-uterine growth restriction in the first months of life, but data beyond those first months were limited. Feeding type also influenced outcomes: infants who were exclusively fed mother's milk showed lower fat mass and higher lean mass compared to those receiving formula. Nutrition in MLPTI is critical for early growth and body composition. Breastfeeding support and adequate early protein and energy intake appear beneficial for early growth. Further longitudinal studies are needed to clarify the lasting impact of early nutrition on growth and body composition in MLPTI.
- Research Article
- 10.1001/jamaophthalmol.2025.5594
- Jan 8, 2026
- JAMA Ophthalmology
- Pia Lundgren + 17 more
Identifying early proteomic profiles in infants who develop severe retinopathy of prematurity (ROP) may reveal targets for preventive interventions to reduce retinal vessel loss and the subsequent risk of severe ROP. To assess early longitudinal profiles of blood protein levels in preterm infants with or without severe ROP and the effect of arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation. This was an exploratory, post hoc analysis of serum proteome profiles in preterm infants in the double-masked Mega Donna Mega (MDM) randomized clinical trial using targeted Olink Proximity Extension Assay proteomics covering 538 analytes. The setting was 3 university hospitals in Sweden and included extremely preterm infants born before 28 weeks of gestational age (GA), from 2016 to 2019. Data were analyzed from January to March 2025. All infants received standard nutrition; additionally, half received enteral lipid supplementation with AA/DHA (100/50 mg/kg per day) from birth to term equivalent age. Longitudinal protein profiles during the first month of life were examined using mixed models for repeated measures, adjusted for GA, study center, and AA/DHA supplementation, and tested for the interaction between severe ROP (stage ≥3 and/or treated) and postnatal age. A total of 177 extremely preterm infants (mean [SD] GA, 25.6 [1.4] weeks; 100 male [56.5%]) were included, of whom 50 (28.2%) developed severe ROP. Of 538 longitudinal analyzed proteins, 109 protein profiles in the first month of life associated with severe ROP, proteins related to immune response, apoptotic processes, blood coagulation, and lipid metabolism. The most pronounced association with severe ROP was a fast rise in fibroblast growth factor 21 (FGF-21; β = 0.68; 95% CI, 0.39-0.97; Q =.002) and tissue plasminogen activator (tPA; β = 0.21; 95% CI, 0.13-0.29; Q <.001) during the first postnatal days. The increase in serum FGF-21 level in the first week of life was associated with lower GA, lower birth weight, low enteral energy intake, and more days receiving mechanical ventilation. No association was observed between AA/DHA supplementation and the proteome. In this post hoc exploratory analysis of data from the MDM randomized clinical trial, a fast rise in FGF-21 levels, a metabolic stress-induced hormone, during the first postnatal days was strongly associated with the development of severe ROP in extremely preterm infants. These findings suggest that early interventions improving bioenergetic status may help prevent severe ROP. ClinicalTrials.gov Identifier: NCT03201588.