Early versus late parenteral nutrition in term and late preterm infants: a randomised controlled trial.

BACKGROUND: There is limited evidence regarding the optimal time to commence parenteral nutrition (PN) in term and late preterm infants. DESIGN: Single-centre, non-blinded, exploratory randomised controlled trial. SETTING: A level-3 neonatal unit in a stand-alone paediatric hospital. PATIENTS: Infants born ≥34 weeks of gestation and ≤28 days, who needed PN. Eligible infants were randomised on day 1 or day 2 of admission. INTERVENTIONS: Early (day 1 or day 2 of admission, N=30) or late (day 6 of admission, N=30) PN. MAIN OUTCOME MEASURES: Plasma phenylalanine and F2-isoprostane levels on day 4 and day 8 of admission. Secondary outcomes were amino-acid and fatty-acid profiles on day 4 and day 8, and clinical outcomes. RESULTS: The postnatal age at randomisation was similar between the groups (2.3 (SD 0.8) vs 2.3 (0.7) days, p=0.90). On day 4, phenylalanine levels in early-PN infants were higher than in late-PN (mean (SD) 62.9 (26.7) vs 45.5 (15.3) µmol/L; baseline-adjusted percentage difference 25.8% (95% CI 11.6% to 39.9%), p<0.001). There was no significant difference in phenylalanine levels between the two groups on day 8. There was no significant difference between the groups for F2-isoprostane levels on day 4 (early-PN mean (SD) 389 (176) vs late-PN 419 (291) pg/mL; baseline-adjusted percentage difference: -4.4% (95% CI -21.5% to 12.8%) p=0.62) and day 8 (mean (SD) 305 (125) vs 354 (113) pg/mL; adjusted mean percentage difference -16.1 (95% CI -34.1 to 1.9) p=0.09).Postnatal growth restriction for weight was less severe in the early-PN group (change in weight z-score from baseline to discharge: -0.6 (0.6) vs -1.0 (0.6); p=0.02). The incidence of hyperglycaemia was greater in the early-PN group (20/30 (66.7%) vs 11/30 (36.7%), p=0.02). CONCLUSIONS: The timing of the commencement of PN did not seem to affect the degree of oxidative stress in critically ill term and late preterm infants. The effect of transiently high plasma phenylalanine with early PN on clinical outcomes requires further investigation. TRIAL REGISTRATION NUMBER: ACTRN12620000324910.

Modeling Developmental Changes in Caffeine Clearance Considering Differences between Pre- and Postnatal Period.

Taguchi et al. reported that postmenstrual age (PMA) is a promising factor in describing and understanding the developmental change of caffeine (CAF) clearance. The aim of the present study was to quantify how developmental changes occur and to determine the effect of the length of the gestational period on CAF clearance. We performed a nonlinear mixed effect model (NONMEM) analysis and evaluated the fit of six models. A total of 115 samples were obtained from 52 patients with a mean age of 34.3 ± 18.2 d. The median values of gestational age (GA) and postnatal age (PNA) were 196 and 31 d, respectively. Serum CAF levels corrected for dose per body surface area (BSA) (C/D ratioBSA) were dependent on PMA rather than PNA, which supports the findings of a previous study. NONMEM analysis provided the following final model of oral clearance: CL/F = 0.00603∙WT∙∙0.877GA ≤ 196 L/h. This model takes into account developmental changes during prenatal and postnatal periods separately. The model successfully described the variation in clearance of CAF. Our findings suggest that the dosage of CAF in preterm infants should be determined based not only on body weight (WT) but also on both PNA and GA.

Serum Neuron-Specific Enolase as a Biomarker of Neonatal Brain Injury-New Perspectives for the Identification of Preterm Neonates at High Risk for Severe Intraventricular Hemorrhage.

Neonatal brain injury (NBI) is a critical condition for preterm neonates with potential long-term adverse neurodevelopmental outcomes. This prospective longitudinal case-control study aimed at investigating the levels and prognostic value of serum neuron-specific enolase (NSE) during the first 3 days of life in preterm neonates (<34 weeks) that later developed brain injury in the form of either periventricular leukomalacia (PVL) or intraventricular hemorrhage (IVH) during their hospitalization. Participants were recruited from one neonatal intensive care unit, and on the basis of birth weight and gestational age, we matched each case (n = 29) with a neonate who had a normal head ultrasound scan (n = 29). We report that serum NSE levels during the first three days of life do not differ significantly between control and preterm neonates with NBI. Nevertheless, subgroup analysis revealed that neonates with IVH had significantly higher concentrations of serum NSE in comparison to controls and neonates with PVL on the third day of life (p = 0.014 and p = 0.033, respectively). The same pattern on the levels of NSE on the third day of life was also observed between (a) neonates with IVH and all other neonates (PVL and control; p = 0.003), (b) neonates with II-IV degree IVH and all other neonates (p = 0.003), and (c) between control and the five (n = 5) neonates that died from the case group (p = 0.023). We conclude that NSE could be an effective and useful biomarker on the third day of life for the identification of preterm neonates at high risk of developing severe forms of IVH.

Cord blood presepsin as a predictor of early-onset neonatal sepsis in term and preterm newborns.

BACKGROUND: To date, no studies on presepsin values in cord blood of term infants with risk factors for early-onset sepsis (EOS) are available, whereas only one study reported presepsin values in cord blood of preterm infants at risk. In this study, we investigated the presepsin values in cord blood of term and preterm infants with documented risk factors for EOS. METHODS: In this single-center prospective pilot study, we enrolled neonates presenting with documented risk factors for EOS. P-SEP levels were assessed in a blood sample collected from the clamped umbilical cord after the delivery in 93 neonates, using a point-of-care device. The primary outcome of our study was to evaluate the role of cord blood P-SEP in predicting clinical EOS in term and preterm infants. RESULTS: During the study period, we enrolled 93 neonates with risk factors for EOS with a gestational age ranging between 24.6 and 41.6 weeks (median 38.0). The median P-SEP value in all infants was 491 pg/ml (IQR 377 - 729). Median cord P-SEP values were significantly higher in infants with clinical sepsis (909 pg/ml, IQR 586 - 1307) rather than in infants without (467 pg/ml, IQR 369 - 635) (p = 0.010). We found a statistically significant correlation between cord P-SEP value at birth and the later diagnosis of clinical sepsis (Kendall's τ coefficient 0.222, p = 0.002). We identified the maximum Youden's Index (best cut-off point) at 579 pg/ml, corresponding to a sensitivity of 87.5% and a specificity of 71.8% in predicting clinical sepsis. CONCLUSIONS: Maximum Youden's index was 579 pg/ml for clinical EOS using cord P-SEP values. This could be the starting point to realize multicenter studies, confirming the feasibility of dosing P-SEP in cord blood of infants with risk factors of EOS to discriminate those who could develop clinical sepsis and spare the inappropriate use of antibiotics.

cfDNA and DNases: New Biomarkers of Sepsis in Preterm Neonates-A Pilot Study.

INTRODUCTION: An early and accurate diagnosis of early onset neonatal sepsis (EONS) and late onset neonatal sepsis (LONS) is essential to improve the outcome of this devastating conditions. Especially, preterm infants are at risk. Reliable biomarkers are rare, clinical decision-making depends on clinical appearance and multiple laboratory findings. Markers of NET formation and NET turnover might improve diagnostic precision. Aim of this study was to evaluate the diagnostic value of NETs in sepsis diagnosis in neonatal preterm infants. METHODS: Plasma samples of neonatal preterm infants with suspected sepsis were collected. Blood samples were assayed for markers of NET formation and NET turnover: cfDNA, DNase1, nucleosome, NE, and H3Cit. All clinical findings, values of laboratory markers, and epidemiological characteristics were collected retrospectively. Two subpopulations were created to divide EONS from LONS. EMA sepsis criteria for neonatal sepsis were used to generate a sepsis group (EMA positive) and a control group (EMA negative). RESULTS: A total of 31 preterm neonates with suspected sepsis were included. Out of these, nine patients met the criteria for sepsis according to EMA. Regarding early onset neonatal sepsis (3 EONS vs. 10 controls), cfDNA, DNase I, nucleosome, and CRP were elevated significantly. H3Cit and NE did not show any significant elevations. In the late onset sepsis collective (6 LONS vs. 12 controls), cfDNA, DNase I, and CRP differed significantly compared to control group.

A hydrophilic interaction liquid chromatography - Tandem mass spectrometry method for the determination of phenylephrine in dried blood spots from preterm infants.

A sensitive and accurate hydrophilic interaction liquid chromatography - tandem mass spectrometry method (HILIC-MS/MS) was developed and validated for the determination of phenylephrine concentration in Dried Blood Spot (DBS) samples from preterm infants, after ocular administration of an ophthalmic solution with phenylephrine. Sample preparation involved the extraction of the analyte from an 85 µL DBS sample with methanol - acetonitrile (50:50, v/v). Chromatographic separation was achieved on an ACQUITY UPLC BEH AMIDE column, under isocratic conditions within a 5 min run. Detection was achieved with a triple quadrupole MS applying electrospray ionization in positive mode. The method was fully validated and proved precise and accurate with in a linear range of 0.59-3.53 ng/ml in blood. The method was developed to provide insights on the level of exposure of infant population to phenylephrine after ocular administration.

Effects of Umbilical Cord Milking on Anemia in Preterm Infants: A Multicenter Randomized Controlled Trial.

OBJECTIVE: This study aimed to investigate whether umbilical cord milking (UCM) prevents and controls anemia in preterm infants, as compared with immediate cord clamping (ICC). STUDY DESIGN: Pregnant women delivering at <34 weeks' gestation in four hospitals were randomly assigned to undergo UCM or ICC from July 2017 to June 2019. Hematological parameters and iron status were collected and analyzed as primary outcomes at 24 hours, 1 week, 2 weeks, and 6 months after delivery. RESULTS: Neonates receiving UCM had significant higher levels of hemoglobin (Hb), hematocrit, and serum iron (p < 0.05). Lower prevalence of anemia and lower need for transfusions were noted in UCM group. Although UCM was associated with prolonged duration of phototherapy, the maximum levels of bilirubin were similar between two groups (p > 0.05). CONCLUSION: UCM is an effective intervention to help preterm infants experience less anemia with the potential to increase blood volume, as seen by higher Hb levels and more enhanced iron stores.

Continuous Glucose Monitoring in the Management of Neonates With Persistent Hypoglycemia and Congenital Hyperinsulinism.

BACKGROUND: Persistent hypoglycemia is common in the newborn and is associated with poor neurodevelopmental outcome. Adequate monitoring is critical in prevention, but is dependent on frequent, often hourly blood sampling. Continuous glucose monitoring (CGM) is increasingly being used in children with type 1 diabetes mellitus, but use in neonatology remains limited. We aimed to introduce real-time CGM to provide insights into patterns of dysglycemia and to support the management of persistent neonatal hypoglycemia. METHODS: This is a single-center retrospective study of real-time CGM use over a 4-year period in babies with persistent hypoglycemia. RESULTS: CGMs were inserted in 14 babies: 8 term and 6 preterm infants, 9 with evidence of congenital hyperinsulinism (CHI). A total of 224 days of data was collected demonstrating marked fluctuations in glucose levels in babies with CHI, with a higher sensor glucose SD (1.52 ±â€…0.79 mmol/L vs 0.77 ±â€…0.22 mmol/L) in infants with CHI compared with preterm infants. A total of 1254 paired glucose values (CGM and blood) were compared and gave a mean absolute relative difference of 11%. CONCLUSION: CGM highlighted the challenges of preventing hypoglycemia in these babies when using intermittent blood glucose levels alone, and the potential application of CGM as an adjunct to clinical care.

Association between blood carboxyhemoglobin level and bronchopulmonary dysplasia in extremely low birthweight infants.

Carboxyhemoglobin (CO-Hb) can be endogenously formed in the presence of oxidative stress and may be elevated in inflammatory lung disease. There is lack of evidence of its relationship with the development of bronchopulmonary dysplasia (BPD) in extremely low birthweight (ELBW) infants. The objective of the study is to evaluate the relationship between blood CO-Hb levels in the first 14 days of life (DOL) in ELBW infants and the development of BPD at 36 weeks postmenstrual age (PMA). This is a retrospective cohort study of 58 ELBW infants born at LAC-USC Medical Center between June 2015 and and June 2019 who survived to 36 weeks PMA. CO-Hb values were collected daily from DOL 1 to DOL 14. BPD definition using the recent 2019 NICHD criteria was used. Multivariate logistic regression was performed to determine the association between blood CO-Hb levels and BPD. Receiver operator curve was used to evaluate the ability of the median fraction of inspired oxygen (FiO2) level used at DOL 11-14 in discriminating absent to mild BPD versus moderate to severe BPD. 58 ELBW infants were included in the study. 24 (41%) were diagnosed with moderate to severe BPD, while 34 (59%) were diagnosed with no to mild BPD. Severity of BPD was fairly discriminated by FiO2 at DOL 11-14, but not with CO-Hb levels at any point within the first 14 DOL. The role and mechanism of CO-Hb production in this population need to be further studied.

Early diagnostic value of C-reactive protein as an inflammatory marker for moderate-to-severe bronchopulmonary dysplasia in premature infants with birth weight less than 1500 g.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a serious respiratory complication in premature infants and moderate-to-severe BPD may affect the long-term quality of life and lack of specific treatment once it happened. Therefore, it is necessary to identify early diagnostic biomarkers for moderate-to-severe BPD. METHODS: This retrospective cohort study included all premature infants with birth weight <1500 g from March 1, 2015 to June 30, 2017. Patients were categorized into mild BPD, moderate-to-severe BPD and non BPD groups. Data collected included patient characteristics, C-reactive protein (CRP) tested at six time points, including 1d (2 h after birth and before the first feeding), 3d, 7d, 2w, 3w, and 4w after birth, and maternal factors. Ordinal regression analysis was used to identify independent predictors of moderate-to-severe BPD and receiver operating characteristic (ROC) curve was used to evaluate the value of CRP as an early diagnostic marker for moderate-to-severe BPD. RESULTS: A total of 831 patients were recruited. BPD occurred in 156/831 premature infants with birth weight less than 1500 g. Lower birth weight (OR = 0.998, 95% CI 0.997-0.999, P = 0.004), higher CRP level 3 days after birth (OR = 1.287, 95% CI 1.195-1.384, P = 0.000), and hemodynamically significant patent ductus arteriosus (HsPDA) (OR = 12.256, 95% CI 3.766-39.845, P = 0.000) were independent risk factors for moderate-to-severe BPD. The area under curve of the CRP level 3 days after birth for diagnosing moderate-to-severe BPD was 0.867 (95% CI, 0.823-0.912, P = 0.000). The sensitivity was 83.0% and the specificity was 78.3% when the cut-off value was set at 4.105 mg/L. CONCLUSION: The CRP level 3 days after birth may be used as an early diagnostic marker for moderate-to-severe BPD in preterm infants who have the risk factors for BPD with birth weight less than 1500 g.

Construção de um bundle para alívio da dor na punção arterial norteado pela Tradução do Conhecimento / Elaboración de un paquete de atención para aliviar el dolor en la punción arterial guiado por Traducción del conocimiento / Elaboration of a bundle for pain relief in arterial puncture guided by Knowledge Translation

RESUMO Objetivo descrever o processo de construção e estratégias de implementação de um bundle para alívio da dor durante a punção arterial do bebê hospitalizado. Métodos estudo de abordagem qualitativa feito em uma unidade de terapia intensiva neonatal, por meio de rodas de conversa realizadas com a equipe de enfermagem. A coleta dos dados ocorreu de fevereiro a maio de 2019. Resultados os encontros levaram à construção de um bundle composto por quatro itens, formatado ludicamente e que deveria ser anexado à incubadora, previamente à realização da punção. Conclusões e Implicações para a prática o processo estimulou a reflexão crítica acerca da própria prática e os profissionais referiram ao uso do bundle como algo possível dentro da unidade, mediante um planejamento para sua inclusão na rotina assistencial. O estudo é pioneiro e apresenta caráter de inovação ao utilizar o bundle para aliviar algo multifacetado como a dor no período neonatal. Apesar de ser algo criado especificamente para a punção arterial, o mesmo pode ser aplicado em demais procedimentos que potencialmente geram dor aguda, uma vez que o foco principal é sempre minimizar o desconforto sentido pelo bebê.

RESUMEN Objetivo describir el proceso de elaboración y las estrategias de implementación de un paquete de atención para aliviar el dolor durante la punción arterial de bebés internados. Métodos estudio de enfoque cualitativo realizado en una unidad de cuidados intensivos neonatales a través de rondas de conversación realizadas con el equipo de Enfermería. La recolección de datos tuvo lugar de febrero a mayo de 2019. Resultados las reuniones derivaron en la elaboración de un paquete de atención que consta de cuatro elementos, formateados en forma lúdica y que deben adjuntarse a la incubadora antes de la punción. Conclusiones e Implicaciones para la práctica El proceso estimuló la reflexión crítica sobre la propia práctica y los profesionales mencionaron el uso del paquete de atención como algo viable dentro de la unidad, a través de la planificación para su inclusión en la rutina de atención. El estudio es pionero y presenta un carácter innovador al utilizar el paquete de atención para aliviar algo multifacético como el dolor en el período neonatal. A pesar de haber sido creado específicamente para la punción arterial, también puede aplicarse en otros procedimientos con potencial para generar dolor agudo, ya que el enfoque principal siempre es minimizar las molestias que siente el bebé.

ABSTRACT Objective to describe the elaboration process and implementation strategies of a bundle for pain relief during arterial puncture in hospitalized infants. Methods a qualitative approach study carried out in a neonatal intensive care unit, through conversation circles held with the Nursing team. Data collection took place from February to May 2019. Results the meetings led to the elaboration of a bundle consisting of four items, in a playful format, and which should be attached to the incubator prior to the puncture. Conclusion and Implications for the practice The process stimulated critical reflection about the practice itself and the professionals mentioned use of the bundle as something feasible within the unit, through planning for its inclusion in the care routine. The study is pioneering and presents an innovative character when using the bundle to relieve a multifaceted issue such as pain in the neonatal period. Despite having been specifically created for arterial puncture, it can also be applied in other procedures that potentially generate acute pain, as the main focus is always to minimize the discomfort felt by the infant.

Immune Profiling of Cord Blood From Preterm and Term Infants Reveals Distinct Differences in Pro-Inflammatory Responses.

Background: Preterm infants are highly vulnerable to infectious disease. While many factors are likely to contribute to this enhanced susceptibility, the immature nature of the preterm immune system is postulated as one key factor. Methods: In our study, we used high-dimensional flow cytometry and cytokine assays to characterise the immune profiles in 25 preterm (range: 30.4-34.1 weeks gestational age) and 25 term infant (range: 37-40 weeks gestational age) cord blood samples. Results: We found that preterm infants exhibit reduced frequencies of monocytes, CD56bright NK cells, CD8+ T-cells, γδ T-cells and an increased frequency of intermediate monocytes, CD4+ T-cells, central memory CD4+ and CD8+ T-cells, Tregs and transitional B-cells compared to term infants. Pro-inflammatory cytokines IL-1ß, IL-6 and IL-17A were lower in preterm infants in addition to chemokines IL-8, eotaxin, MIP-1α and MIP-1ß. However, IL-15 and MCP-1 were higher in preterm infants. Conclusion: Overall, we identify key differences in pro-inflammatory immune profiles between preterm and term infants. These findings may help to explain why preterm infants are more susceptible to infectious disease during early life and facilitate the development of targeted interventions to protect this highly vulnerable group.

Correlation between hyperglycemia and glycated albumin with retinopathy of prematurity.

To determine the association between hyperglycemia, glycated albumin (GlyA) and retinopathy of prematurity (ROP). Prospective study of all infants under ROP screening from March 2017 to July 2019. All demographic, clinical and laboratory data were collected. Glucose was measured at birth and every 8 h for the first week and serum GlyA was evaluated at birth, 1st, 2nd and 4th weeks after birth. Reference range for GlyA was obtained. Univariate logistic regression was used to examine risk factors for ROP followed by multivariate regression. A total of 152 infants were included in the study. Median gestational age was 30 weeks and median birth weight 1240 g. Thirty-three infants (21.7%) had ROP. Hyperglycemia was present in 24 (72.7%) infants diagnosed with any ROP versus 6 (0.05%) in those without ROP. Median GlyA at birth, 1st, 2nd and 4th and respective reference ranges were 8.50% (6.00-12.65), 8.20% (5.32-11.67), 8.00% (5.32-10.00) and 7.90% (5.30-9.00) respectively. After multivariate logistic regression, hyperglycemia but not GlyA, remained a significant risk factor for ROP overpowering the other recognized risk factors (Exp (B) 28.062, 95% CI for Exp(B) 7.881-99.924 p < 0.001). In our cohort, hyperglycemia but not GlyA, remained a significant risk factor for ROP overpowering the other recognized risk factors.

An analysis of perinatal factors of low T3 syndrome in preterm neonates with a gestational age of 28-35 weeks.

OBJECTIVE: Low triiodothyronine syndrome (LT3S) is a common endocrine disease in preterm neonates. Various serious acute or chronic diseases result in LT3S. Few studies have investigated the causal relationship between perinatal factors and LT3S in preterm neonates with a gestational age (GA) of 28-35 weeks. The present study comprehensively analyzed the perinatal factors of LT3S in preterm neonates. METHODS: This was a retrospective study of neonates with and without LT3S from January 2018 to November 2019. Compared to 206 preterm neonates without LT3S, 158 neonates were diagnosed with LT3S, excluding neonates with congenital malformations, other endocrine diseases, genetic diseases and inherited metabolic diseases. RESULTS: Five perinatal risk factors for LT3S were confirmed using univariate and multivariate analyses: smaller gestational age, lower birth weight, respiratory distress syndrome (RDS), neonatal sepsis, and dopamine use. CONCLUSIONS: LT3S in preterm neonates was associated with multiple perinatal factors, including smaller gestational age, lower birth weight, RDS, sepsis, and dopamine use. Preterm neonates with a GA of 28-35 weeks who are exposed to a series of high-risk perinatal factors must be closely observed, diagnosed early and treated for primary diseases promptly to reduce the occurrence of LT3S and improve the outcomes.Key Message:Few studies have investigated the relationship between perinatal factors and Low triiodothyronine syndrome (LT3S) in preterm neonates with a gestational age (GA) of 28-35 weeks.LT3S was associated with multiple perinatal factors, including smaller gestational age, lower birth weight, respiratory distress syndrome (RDS), sepsis, and dopamine use.

Inflammatory biomarkers in very preterm infants during early intravenous paracetamol administration.

BACKGROUND: Paracetamol promotes early closure of patent ductus arteriosus (PDA), and it may affect inflammation after preterm birth. OBJECTIVE: The aim of this study was to evaluate the association between paracetamol treatment and serum inflammatory biomarkers in very preterm infants with respiratory distress. STUDY DESIGN: The infants were randomly assigned to intravenous paracetamol or placebo during the first 4 days of life, and others received a lower dose of paracetamol unblinded. Serum samples were used for the analysis of 10 cytokines, C-reactive protein (CRP) and malondialdehyde (MDA). The impact of paracetamol on the biomarkers was evaluated, based on the levels during the early (<60 h) and the later (60-120 h) postnatal age. RESULTS: Altogether, 296 serum samples from 31 paracetamol and 25 placebo group infants were analysed. Paracetamol had no effect on cytokine levels during the first 60 h when most induced PDA contractions took place. Later paracetamol treatment was associated with lower serum levels of several cytokines, including interleukin (IL-) 10, interferon gamma-induced protein (IP-) 10, and monocyte chemoattractant protein-1. CRP levels were lower in the paracetamol group during the early treatment. Amongst the infants who had severe morbidities, MDA was higher (p = .045), regardless of paracetamol treatment. CONCLUSION: No significant differences in the cytokine levels were evident between the treatment and placebo groups. However, during early treatment, CRP levels were lower in the paracetamol group. To clarify whether this was due to a decrease in cardiopulmonary distress, or a distinct anti-inflammatory effect, requires further studies.

The Distinct Immune Nature of the Fetal Inflammatory Response Syndrome Type I and Type II.

Fetal inflammatory response syndrome (FIRS) is strongly associated with neonatal morbidity and mortality and can be classified as type I or type II. Clinically, FIRS type I and type II are considered as distinct syndromes, yet the molecular underpinnings of these fetal inflammatory responses are not well understood because of their low prevalence and the difficulty of postdelivery diagnosis. In this study, we performed RNA sequencing of human cord blood samples from preterm neonates diagnosed with FIRS type I or FIRS type II. We found that FIRS type I was characterized by an upregulation of host immune responses, including neutrophil and monocyte functions, together with a proinflammatory cytokine storm and a downregulation of T cell processes. In contrast, FIRS type II comprised a mild chronic inflammatory response involving perturbation of HLA transcripts, suggestive of fetal semiallograft rejection. Integrating single-cell RNA sequencing-derived signatures with bulk transcriptomic data confirmed that FIRS type I immune responses were mainly driven by monocytes, macrophages, and neutrophils. Last, tissue- and cell-specific signatures derived from the BioGPS Gene Atlas further corroborated the role of myeloid cells originating from the bone marrow in FIRS type I. Collectively, these data provide evidence that FIRS type I and FIRS type II are driven by distinct immune mechanisms; whereas the former involves the innate limb of immunity consistent with host defense, the latter resembles a process of semiallograft rejection. These findings shed light on the fetal immune responses caused by infection or alloreactivity that can lead to deleterious consequences in neonatal life.

Plasma levels of amino acids and derivatives in retinopathy of prematurity.

Background: Retinopathy of prematurity (ROP) is a retinal disease that causes blindness in premature infants. This study aimed to reveal the changes in amino acids and derivatives in the plasma of ROP patients compared with premature infants without ROP. Methods: Metabolomics targeting amino acids and their derivatives was conducted to assess their plasma levels in ROP patients (n=58) and premature infants without ROP (n=25), and KEGG pathway analysis was used to identify the involved pathways. Results: Among the 31 assessed metabolites, the levels of 4 amino acids were significantly altered in the ROP group. Creatinine was downregulated in the plasma of the ROP patients, while the levels of citrulline, arginine, and aminoadipic acid were upregulated in the ROP group. Significant correlations were identified between the ROP stage and plasma levels of citrulline, creatinine, and aminoadipic acid. The involved pathways included biosynthesis of amino acids, arginine and proline metabolism, and arginine biosynthesis. Conclusion: The plasma levels of citrulline, creatinine, arginine, and aminoadipic acid were significantly changed in ROP patients. These metabolites could be considered potential biomarkers of ROP, and their related metabolic pathways might be involved in ROP pathogenesis.