ABSTRACT
Objetivo: estimar a prevalência de Aleitamento Materno Exclusivo (AME) entre gemelares pré-termos e investigar o efeito de nascer gemelar e pré-termo no AME na alta hospitalar. Método: coorte prospectiva de recém-nascidos em uma instituição localizada no Rio de Janeiro, no período de 13 de março de 2017 a 12 de outubro de 2018. Dados coletados em questionário e prontuário médico. Foi utilizado DAG para construção do modelo conceitual, análise exploratória dos dados e regressão logística múltipla. Resultados: a prevalência de AME na alta hospitalar de gemelares pré-termos foi de 47,8%. Pré-termos apresentaram maior chance de não estarem em AME na alta hospitalar. Não gemelares apresentaram maior chance de não estarem em AME na alta hospitalar. Conclusão: pouco mais da metade dos gemelares pré-termo não estavam em AME na alta hospitalar. Prematuros tiveram maior chance de não estarem em AME. Não gemelares pré-termo apresentaram maior chance de não estarem em AME.
Objective: to estimate the prevalence of Exclusive Breastfeeding (EBF) in preterm twins and to investigate the effect of twin and preterm birth on EBF at hospital discharge. Method: prospective cohort of newborns in an institution located in Rio de Janeiro, from March 13, 2017, to October 12, 2018. Data collected through a questionnaire and medical records. A DAG was used to build the conceptual model, exploratory data analysis and multiple logistic regression. Results: prevalence of EBF at hospital discharge of preterm twins of 47.8%. Preterm infants were more likely to not be on EBF at hospital discharge. Non-twins were more likely to not be on EBF at hospital discharge. Conclusion: just over half of preterm twins were not on EBF at hospital discharge. Preterm infants had a greater chance of not being on EBF. Preterm non-twins were more likely to not be on EBF.
Objetivo: estimar la prevalencia de Lactancia Materna Exclusiva (LME) entre gemelos prematuros y investigar el efecto de nacer gemelo y prematuro en la LME al momento del alta hospitalaria. Método: cohorte prospectiva de recién nacidos en una institución ubicada en Rio de Janeiro, entre 13//marzo/2017 y 12/octubre/2018. Los datos se recolectaron mediante cuestionario y expediente médico. Se utilizó DAG para la construcción del modelo conceptual, análisis exploratorio de los datos y regresión logística múltiple. Resultados: la prevalencia de LME en el alta hospitalaria de gemelos prematuros fue del 47,8%. Los prematuros tuvieron mayor probabilidad de no estar en LME en el alta hospitalaria. Los no gemelares tuvieron mayor probabilidad de no estar en LME en el alta hospitalaria. Conclusión: poco más de la mitad de los gemelos prematuros no estaban en LME en el alta hospitalaria. Los prematuros tuvieron mayor probabilidad de no estar en LME. Los no gemelos prematuros presentaron mayor probabilidad de no estar en LME.
ABSTRACT
Purpose: To observe the vascular development results of tertiary anti-vascular endothelial growth factor (anti-VEGF) therapy following spontaneous second reactivation of retinopathy of prematurity (ROP). Methods: This retrospective study included 22 infants (42 eyes) with Type 1 or aggressive ROP (A-ROP) who received three anti-VEGF drug treatments for ROP from January 2018 to December 2022. The vascular growth, possible associated risk factors, and the retinal vascularization (DB/DF ratio) were assessed. Results: The mean follow-up was 17.6 months. After the 3rd intravitreal injection, seven eyes showed complete vascularization (Group 1), while the remaining 35 eyes demonstrated persistent avascular retina (PAR) (Group 2). In Group 2, 17 eyes maintained a stable state and were classified in the regression subgroup. The other 18 eyes developed a 3rd reactivation (reactivation subgroup) and were treated with laser photocoagulation (LPC).Birth weight (BW) was significantly lower in Group 2 than in Group 1 (p < 0.001). The decision tree analysis shows that only infants weighing more than 1,250 g (17.50%) had a chance to achieve complete retinal vascularization. The possibility of PAR was higher in patients with BW <1,250 g than ≥1,250 g (70.00% vs. 12.50%). In addition, most infants with BW ≥ 1,290 g and initial ROP disease in Zone I or posterior Zone II developed PAR. Conclusion: Tertiary IVR can successfully treat a second ROP reactivation and improve peripheral retinal vascularization. BW is the most significant factor related to complete retinal vascularization. Our decision tree model may be helpful in predicting the prognosis of anti-VEGF drugs in the event of a second ROP reactivation.
ABSTRACT
Very preterm birth (< 32 weeks' gestational age) is associated with later social and emotional impairments, which may result from enhanced vulnerability of the limbic system during this period of heightened vulnerability. Evidence suggests that early procedural pain may be a key moderator of early brain networks. In a prospective cohort study, neonates born very preterm (< 30 weeks' gestation) underwent MRI scanning at term-equivalent age (TEA) and clinical data were collected (mechanical ventilation, analgesics, sedatives). Procedural pain was operationalized as the number of skin breaking procedures. Amygdala volumes were automatically extracted. The Strengths and Difficulties questionnaire was used to assess social-emotional outcomes at 5 years of age (mean age 67.5 months). General linear models were employed to examine the association between neonatal amygdala volumes and social-emotional outcomes and the timing and amount of procedural pain exposure (early within the first weeks of life to TEA) as a moderator, adjusting for biological sex, gestational age, 5-year assessment age, days of mechanical ventilation and total cerebral volumes. A total of 42 preterm infants participated. Right amygdala volumes at TEA were associated with prosocial behaviour at age 5 (B = -0.010, p = 0.005). Procedural pain was found to moderate the relationship between right amygdala volumes in the neonatal period and conduct problems at 5 years, such that early skin breaking procedures experienced within the first few weeks of life strengthened the association between right amygdala volumes and conduct problems (B = 0.005, p = 0.047). Late skin breaking procedures, experienced near TEA, also strengthened the association between right amygdala volumes and conduct problems (B = 0.004, p = 0.048).
HIGHLIGHTS: â Preterm birth is associated with social-emotional challenges.â Amygdala volumes at term equivalent age were assessed in relation to preschool social-emotional outcomes.â Larger right amygdala volumes at term-equivalent age were associated with impaired prosocial behaviour at age 5.â Procedural pain moderated the relationship between neonatal amygdala volumes and conduct problems at age 5, with early or late skin breaking procedures strengthening this association.â Dysregulated growth and maturation of the amygdala in preterm neonates were associated with differences in social functioning at 5 years old, with early life procedural pain playing a moderating role.
ABSTRACT
PURPOSE: Melatonin has promising protective effects for retinopathy. However, its roles in retinopathy of prematurity (ROP) and the underlying mechanisms remain unknown. We aimed to explore its roles and mechanisms in a ROP model. METHODS: Hematoxylin and eosin staining were used to observe the morphology of the retina. Immunofluorescence was used to detect positive (Nrf2+ and VEGF+) cells. Immunohistochemistry was used to detect the level of nuclear expression of PCNA in retinal tissue. Transmission electron microscope (TEM) was used to observe the morphology and structure of pigment cells. qRT-PCR was used to assay the expression of miR-23a-3p, Nrf2, and HO-1. Western blotting was used to detect the expression of Nrf2, HO-1, ß-actin, and Lamin B1. RESULTS: Melatonin or miR-23a-3p antagomir treatment could ameliorate the Oxygen-induced pathological changes, increased the expression of Nrf2 and HO-1, SOD, and GSH-Px, and decreased the expression of VEGF, miR-23a-3p, MDA and the apoptosis in the ROP model. Further target prediction and luciferase reporter assays confirmed the targeted binding relationship between miR-23a-3p and Nrf2. CONCLUSION: Our study showed that melatonin could ameliorate H2O2-induced apoptosis and oxidative stress injury in RGC cells by mediating miR-23a-3p/Nrf2 signaling pathway, thereby improving retinal degeneration.
ABSTRACT
INTRODUCTION: Early prediction and timely treatment are essential for minimizing the risk of visual loss or blindness of retinopathy of prematurity, emphasizing the importance of ROP screening in clinical routine. OBJECTIVE: To establish predictive models for ROP occurrence based on the risk factors using artificial neural network. METHODS: A cohort of 591 infants was recruited in this retrospective study. The association between ROP and perinatal factors was analyzed by univariate analysis and multivariable logistic regression. We developed predictive models for ROP screening using back propagation neural network, which was further optimized by applying genetic algorithm method. To assess the predictive performance of the models, the areas under the curve, sensitivity, specificity, negative predictive value, positive predictive value and accuracy were used to show the performances of the prediction models. RESULTS: ROP of any stage was found in 193 (32.7%) infants. Twelve risk factors of ROP were selected. Based on these factors, predictive models were built using BP neural network and genetic algorithm-back propagation (GA-BP) neural network. The areas under the curve for prediction models were 0.857, and 0.908 in test, respectively. CONCLUSIONS: We developed predictive models for ROP using artificial neural network. GA-BP neural network exhibited superior predictive ability for ROP when dealing with its non-linear clinical data.
Subject(s)
Gestational Age , Neural Networks, Computer , Retinopathy of Prematurity , Humans , Retinopathy of Prematurity/diagnosis , Retinopathy of Prematurity/epidemiology , Retrospective Studies , Infant, Newborn , Female , Male , Risk Factors , Predictive Value of Tests , ROC Curve , Neonatal Screening/methods , AlgorithmsABSTRACT
BACKGROUND: Human milk banks are essential facilities to provide donated human milk (DHM) to preterm and term infants with health complications. Little is known regarding milk bank donors and how their characteristics may influence the particularities of the donation process. The present study aims to assess characteristics of donors and their newborns to identify associations with the amount of DHM and initiation and donation time, during the first and second year of the milk bank operation in Córdoba, Spain. METHODS: This cross-sectional study was conducted in three periods: pre-opening of the milk bank (PRE) including all women who gave birth to a newborn between January - May 2017 and were hospital users; donors in the first year after the opening (Period 1 (P1): April 2019 - March 2020); and in the second year (P2: April 2020 - March 2021). For P1 and P2, DHM data were recorded. The relationships between donor and newborn characteristics and the donation process were examined using univariable and regression models. RESULTS: From 391 women interviewed in the PRE period, 55 (14%) showed intention to donate. In P1 and P2, there were 51 and 25 human milk (HM) donors, respectively. Age, gestational age (GA) and parity were similar between periods. In P2, a higher proportion of donors had higher education (P1: 46%; P2: 70.8%, p = 0.045). Around 40% of donors in both periods were on maternity leave. In P1, donors who had low birth weight infants (< 2500 g) donated more HM than those with infants weighing ≥ 2500 g (p = 0.020). In P2, women whose GA was < 37 weeks donated a higher volume vs. those with ≥ 37 weeks (p = 0.002). Maternity leave was linked to a shorter initiation time for donations in both periods (P1: p = 0.002; P2: p < 0.001). CONCLUSIONS: Data obtained from a Spanish human milk bank indicate that prematurity and low birth weight appear to influence the amounts of DHM. Employment status might be a decisive factor in initiating HM donation. Additional efforts are required to identify shared donor characteristics that influence the initiation and volume of donation.
Subject(s)
Milk Banks , Milk, Human , Humans , Cross-Sectional Studies , Spain , Female , Infant, Newborn , Adult , Tissue Donors/psychology , Young Adult , PregnancyABSTRACT
Background: Circadian rhythms impact metabolism and the therapeutic effects of drugs. The purpose of this study was to determine the association between PER and CRY polymorphisms and caffeine citrate treatment response in infants with apnea of prematurity. Methods: A total of 221 preterm infants of gestational age <34 weeks were included in this study (160 in the response group and 61 in the non-response group). The propensity score matching method was used to perform a 1:1 matching for all premature infants, and the general characteristics and clinical outcomes of the two groups were compared. The association between polymorphisms of the circadian transcription repressors PER and CRY and caffeine citrate treatment response in infants with apnea of prematurity was analyzed with co-dominant, dominant, recessive, and over-dominant models, as well as analysis of alleles. Generalized multifactor dimensionality reduction (GMDR) analysis was used to analyze the interaction between the PER and CRY genes. Results: After propensity score matching, 45 preterm infants were included in each of the response and non-response groups, and there were no statistically significant differences in general characteristics between the two groups (P > 0.05). Infants in the non-response groups had a higher incidence of moderate and severe bronchopulmonary dysplasia (BPD) (P = 0.043), retinopathy of prematurity (ROP) (P = 0.035), and invasive ventilation (P = 0.027), and their duration of oxygen use (P = 0.041) was longer. When corrected for false discovery rate, the PER3 rs228669 recessive model (P FDR = 0.045) and the over-dominant model (P FDR = 0.045) were both associated with caffeine citrate treatment response. Preterm infants with the rs228669 CC genotype had a significantly lower rate of caffeine citrate non-response in the recessive model (OR = 0.28, 95% CI = 0.12-0.66), which was significantly higher in preterm infants with the CT genotype in the over-dominant model (OR = 4.18, 95% CI = 1.64-10.66). GMDR analysis revealed an interaction between the PER and CRY genes (P < 0.05). Conclusions: Circadian rhythms may play a role in the response of premature infants to caffeine citrate, and polymorphisms of the PER and CRY genes may influence the effectiveness of caffeine citrate treatment for apnea of prematurity.
ABSTRACT
BACKGROUND: Premature and small-for-gestational-age (SGA) infants tend to have long-term growth morbidities such as short stature, failure to thrive, and obesity. Although most of these infants show catch-up growth at 2-4 years of age, they are still more susceptible to childhood obesity and related metabolic disorders. Those who fail to achieve catch-up will suffer from pathological short stature and neurodevelopmental impairment through adulthood. This study aims to depict the growth pattern of premature or SGA infants and their growth morbidities in Taiwan. METHODS: Data were obtained from a nationally representative cohort of 24,200 pairs of postpartum women and newborns in the Taiwan Birth Cohort Study (TBCS), using structured questionnaire interviews. A total of 16,358 infants were included and three follow-up surveys were completed at 6, 18, and 36 months after the deliveries. We constructed growth curves to conduct an in-depth investigation into anthropometric data, applying a linear mixed model. Logistic regression was used to model the relevant outcomes, with adjustment for various potential confounding factors. RESULTS: Despite being born shorter and lighter, preterm and SGA infants generally showed catch-up growth and had no higher odds ratios (ORs) of developing short stature or failure to thrive compared to appropriate-for-gestational-age (AGA) term infants before 3 years of age. Preterm SGA infants, particularly females, had higher ORs for obesity at the 36-month follow-up. CONCLUSION: This is the first nationwide population-based study depicting the growth of SGA infants in Taiwan. The growth patterns of preterm and term SGA infants are different from those of preterm and term AGA infants. Further research is necessary to understand the growth trajectories of preterm and SGA infants and their associations with later diseases.
ABSTRACT
Background: Preeclampsia is a potentially life-threatening hypertensive pregnancy disorder that carries an acute risk of an unfavorable outcome of the pregnancy but also has consequences for the long-term health of the mother. Women who develop the early form of pre-eclampsia before the 32nd week of pregnancy have the highest risk and are also the most difficult to treat. The severity of pre-eclampsia is not characterized uniformly in Germany, so that the indication for delivery is rather individualized. The aim of this study was to reach a consensus on parameters that could serve as criteria for describing the severity of pre-eclampsia based on the urgency of delivery. To this end, a Delphi procedure was used to present a scenario in which a woman was admitted for preeclampsia before 32 gestational weeks and after completion of antenatal steroid therapy. Methods: Clinicians specialized in maternal-fetal medicine from German-speaking countries completed five rounds of a modified Delphi questionnaire. Presented parameters were selected by the section "Hypertensive Pregnancy Diseases and Fetal Growth Restriction" of the German Society of Gynecology and Obstetrics after reviewing the literature. These included objectifiable laboratory or clinical parameters as well as subjective symptoms of the patient. In addition, nine fetal parameters were taken into account. The clinicians were asked to rate presented parameters as an indication for delivery on a Likert scale from 0 to 4 (no indication to absolute indication without delay). For each item, the predefined cut-off for group consensus was ≥ 70% agreement. Results: A total of 126 experts were approached. Sixty-nine experts (54.8%) took part in the first round; of those 50 completed the entire Delphi procedure. A consensus was reached on 14 parameters to be considered rapid preparation for delivery without delay (4 points on the Likert scale). These were among others hepatic hematoma or liver capsule rupture, acute liver failure with fulminant coagulation disorder or disseminated intravascular coagulation, eclampsia, pathologic findings in imaging (e.g. cMRI) or electrocardiogram arranged for new onset of headache or retrosternal pain, respectively. Twenty-six parameters were rated as factors that should be considered in the decision without being absolute (1 to 3 points), and 13 parameters should have no influence on the decision to deliver (0 points). No consensus on severe hypertension as an indication for delivery could be reached for blood pressure values below 220/140 mmHg. Conclusion: A consensus was reached on whether to deliver in preeclampsia typic clinical findings and symptoms. The results can serve as guidance for current clinical practice and for the definition of clinical endpoints in intervention studies. Nevertheless, the isolated criteria are a theoretical construction since the combined deterioration or summation of several factors rather than a single factor most likely influences the decision to deliver and reflect the severity of preeclampsia. Moreover, the degree of hypertension as an indication for delivery remains controversial, unless the patient suffers additionally from complaints. Future research should be enforced to incorporate long-term risks for the mother into a decision aid.
ABSTRACT
Background: Restriction of PBF in infants born with CHD is often required to avoid pulmonary over-circulation prior to definitive intervention. The current standard is to surgically place pulmonary artery bands, but these have limitations and are associated with complications. Objectives: The purpose of this study was to a single-center experience with a relatively novel technique to percutaneously restrict pulmonary blood flow (PBF) in select infants with congenital heart disease (CHD). Methods: Patients were selected to undergo this procedure either due to low birth weight or prematurity. All of them had CHD that would result in over-circulation without control of PBF. By a percutaneous method, modified vascular plug devices were placed in the bilateral branch pulmonary arteries. Results: Seven neonates with CHD resulting in left-sided obstruction underwent this procedure. All patients demonstrated evidence of restricted PBF with a decrease in mean oxygen saturation from 95% to 84%. One patient required pulmonary artery band placement due to over-circulation 5 days after the procedure. All patients proceeded to full surgical intervention without device embolization or need for pulmonary arterioplasty. Hemodynamics demonstrated adequate limitation of PBF in 5 patients who underwent presurgical cardiac catheterization with a mean pulmonary vascular resistance of 1.52 WU × m2 and a mean transpulmonary gradient of 5.9 mm Hg. Conclusions: Percutaneous PBF restriction appears to be safe and a less invasive option to delay surgical intervention in a select population to allow for somatic growth and gestational maturation. It results in a decrease in the total number of sternotomies.
ABSTRACT
BACKGROUND: Retinopathy of prematurity (ROP) is an important cause of visual morbidity among preterm infants. The objective of the study was to assess the relationship between the initial hematological parameters of the complete blood count (CBC) and ROP development in preterm neonates. METHOD: This retrospective cohort study was conducted in a neonatal intensive care unit in Odisha. The hematological parameters of the CBC conducted within the first 48 hours of age, demographic characteristics, neonatal morbidities, and ROP screening findings of preterm neonates (gestational age <34 weeks) were analyzed. Independent risk factors associated with ROP development were identified in a multivariate logistic regression model. RESULT: A total of 43 (29.1%) out of 148 neonates had any of the ROP stages (stage 1-26, 2-08, and 3-09). Birth weight (aOR 0.003; 95% CI 0.00, 0.11);hemoglobin (Hb) level (aOR 0.70; 95% CI 0.54, 0.90); presence of respiratory distress syndrome (RDS) (aOR 7.61; 95% CI 1.5, 36.39); and need for packed red blood cell (PRBC) transfusion (aOR 4.26; 95% CI 1.1, 16.44) were independently associated with ROP development. The odds of ROP were higher among the neonates with initial Hb 10.5-15.4 g/dL (OR (95% CI) 3.7(1.5, 8.9), p=0.003) and for neonates with Hb 15.4-17.3 g/dL (OR (95% CI) 2.5(1.01, 6.16), p=0.047) in comparison to neonates with initial Hb >17.3 g/dL. CONCLUSION: Preterm neonates with a lower level of Hb during the early postnatal days are at higher risk for ROP development and need to be prioritized for screening.
ABSTRACT
Introduction: The aim of this paper is to delve into the emotional and psychological challenges that fathers face as they navigate the complexities of having a preterm infant in the NICU and in an unprecedented sanitary context. Methods: We used three data collection methods such as interviews (narrative and the Clinical Interview for Parents of High-risk Infants- CLIP) and the Edinburgh Postnatal Depression Scale (EPDS) to gain a comprehensive understanding of the cases. Results: The following analysis explores two individuals' personal experiences of becoming a first-time father during the first wave of the COVID-19 pandemic through a close examination of two superordinate themes: "A series of separations through the experienced COVID- 19 restrictions" and "Moments of connection." The transition to fatherhood is essentially with a medicalized form of connection with their newborn and the perceived paternal identity. In terms of temporality, these fathers experienced a combination of concerns about their infants' long-term development and COVID-19 health concerns. Furthermore, they showed indications of phobic or hypochondriac tendencies using a psychoanalytic framework, along with an increased risk of postpartum depression.
ABSTRACT
Purpose: To describe fluorescein angiography (FA) parameters observed in premature neonates with retinopathy of prematurity (ROP). Design: Retrospective case series. Subjects: Patients with ROP who underwent FA imaging using Retcam at Holtz Children's Hospital from November 2014 to October 2022. Methods: Fluorescein angiography images of the included patients were analyzed with a focus on the timing of angiography phases, including choroidal flush, retinal, and recirculation phases. Gestational age, birth weight (BW), age at imaging, treatment choice, and any FA complications were documented. Main Outcome Measures: Dose of fluorescein administered, onset and duration of each angiography phase, and FA findings in ROP-treated patients. Results: A total of 72 images of 72 eyes were reviewed. Image quality was deemed suitable for inclusion in 64 eyes (88.9%) of 43 patients. The mean gestational age and BW at birth were 24.4 ± 1.9 weeks and 607.8 ± 141.3 g, respectively. The mean postmenstrual age at FA imaging was 50.5 ± 40.8 weeks. All eyes (100%) received treatment with intravitreal injection of anti-VEGF at a mean age of 35.5 ± 2.4 weeks. The onset and duration of angiography phases were relatively variable within the cohort. Choroidal flush occurred at a mean time of 12.2 seconds (range: 6-22 seconds). A subsequent retinal phase was documented at a mean time of 11.96 seconds (range: 3-22 seconds). Recirculation phase was complete at an average time of 2.15 minutes (range: 1-5.45 minutes) postfluorescein injection. None of patients developed allergic reactions to fluorescein injection, such as rash, respiratory distress, tachycardia, fever, or local injection site reactions. Conclusions: Angiographic phases on FA in preterm infants with ROP are variable and may occur earlier than the established references for adults. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
ABSTRACT
BACKGROUND: This research aimed to identify the clinical profile and risk factors of retinopathy of prematurity (ROP) among "at-risk" newborns treated at a sick newborn care unit (SNCU) located at high altitude in North India, with the intention of contributing to formulate regional and national ROP screening guidelines. MATERIALS AND METHODS: In a prospective observational study from 2021 to 2022, outborn and inborn babies eligible for ROP screening were screened. RESULTS: Total 39/122 screened neonates had laser for Type 1 ROP, and 22/39 (56.4%) had aggressive ROP (AROP). The average birth weight (BW) was 1803.87 g, and the average gestational age was 34 weeks. Respiratory distress, bronchopulmonary dysplasia, sepsis, and apnea were present in 57.3%, 13%, 52.5%, and 25.4%, respectively. Sight-threatening ROP was present in 50% below 28+6 weeks, 27% between 29 and 30+6 weeks, 52% between 31 and 33+6 weeks, and 15% with gestation >34 weeks. Two babies with Type 1 ROP weighed >2 kg and one had AROP. Upon regression analysis, BW <1500 g, gestation <32 weeks, oxygen >48 h, clinical sepsis, total SNCU stay >14 days, continuous positive airway pressure support with oxygen >50%, and >10 days to achieve full feeds were associated with severe ROP. Caffeine to treat apnea and kangaroo mother care reduced ROP. None had short-term unfavorable outcome. CONCLUSION: With similar infrastructure and work force shortage in most SNCUs, these findings can be generalized. The burden of Type 1 and AROP is increasing, as seen in higher gestation and BWs. This needs revision of ROP screening criteria at local and national level. It is crucial to emphasize on the importance of pediatrician and ophthalmologist collaboration, early ROP screening, diagnosis, and treatment to stop disease progression to severe ROP.
ABSTRACT
Reduction-oxidation (redox) chemistry plays a vital role in human homeostasis. These reactions play critical roles in energy generation, as part of innate immunity, and in the generation of secondary messengers with various functions such as cell cycle progression or the release of neurotransmitters. Despite this cornerstone role, if left unchecked, the body can overproduce reactive oxygen species (ROS) or reactive nitrogen species (RNS). When these overwhelm endogenous antioxidant systems, oxidative stress (OS) occurs. In neonates, OS has been associated with retinopathy of prematurity (ROP), leukomalacia, and bronchopulmonary dysplasia (BPD). Given its broad spectrum of effects, research has started to examine whether OS plays a role in necrotizing enterocolitis (NEC). In this paper, we will discuss the basics of redox chemistry and how the human body keeps these in check. We will then discuss what happens when these go awry, focusing mostly on NEC in neonates.
Subject(s)
Enterocolitis, Necrotizing , Oxidation-Reduction , Oxidative Stress , Reactive Nitrogen Species , Reactive Oxygen Species , Humans , Enterocolitis, Necrotizing/metabolism , Enterocolitis, Necrotizing/pathology , Reactive Oxygen Species/metabolism , Infant, Newborn , Reactive Nitrogen Species/metabolism , Antioxidants/metabolism , AnimalsABSTRACT
Retinopathy of prematurity (ROP) is a vascular disorder affecting the retinas of preterm infants. This condition arises when preterm infants in incubators are exposed to high oxygen levels, leading to oxidative stress, inflammatory responses, and a downregulation of vascular endothelial growth factors, which causes the loss of retinal microvascular capillaries. Upon returning to room air, the upregulation of vascular growth factors results in abnormal vascular growth of retinal endothelial cells. Without appropriate intervention, ROP can progress to blindness. The prevalence of ROP has risen, making it a significant cause of childhood blindness. Current treatments, such as laser therapy and various pharmacologic approaches, are limited by their potential for severe adverse effects. Therefore, a deeper understanding of ROP's pathophysiology and the development of innovative treatments are imperative. Natural products from plants, fungi, bacteria, and marine organisms have shown promise in treating various diseases and have gained attention in ROP research due to their minimal side effects and wide-ranging beneficial properties. This review discusses the roles and mechanisms of natural products that hold potential as therapeutic agents in ROP management.
Subject(s)
Biological Products , Retinopathy of Prematurity , Retinopathy of Prematurity/drug therapy , Retinopathy of Prematurity/therapy , Retinopathy of Prematurity/metabolism , Humans , Biological Products/therapeutic use , Biological Products/pharmacology , Infant, Newborn , Animals , Infant, PrematureABSTRACT
Background/Objectives: Prematurity rates remain high and represent a challenge for the public health systems of any country, with a high impact on neonatal mortality. This study aimed to evaluate the frequency and environmental and maternal-fetal risk factors for premature birth in a cohort of parturient women, with their newborns monitored in a neonatal intensive care unit at a private reference hospital. Methods: A cohort was carried out between 2013 and 2018 among parturient women living in a capital city in the Northeast of Brazil whose newborns were admitted to the neonatal intensive care unit. This study was approved by the Research Ethics Committee of the University of Fortaleza. The information collected comprised data from both medical records and hydrosanitary data from maternal homes. Results: The prevalence of prematurity among live births (n = 9778) between 2013 and 2018 at this hospital was 23%. The frequency of prematurity among those eligible (n = 480) was 76.9%, and the frequency of eligible premature babies (n = 369) in relation to the total number of births in this period was 3.8%. In the multivariate analysis, the significant risk factors for prematurity were primigravida (RR = 1.104, 95%CI: 1.004-1.213) and hypertensive syndromes during pregnancy (RR = 1.262, 95%CI: 1.161-1.371), and the significant protective factor was the highest number of prenatal consultations (RR = 0.924, 95%CI: 0.901-0.947). Conclusions: This study contributes to providing greater visibility to prenatal care and the understanding of complications during pregnancy and childbirth care. These results indicate the need to implement public policies that promote improvements in the population's living conditions and care for pregnant women to reduce premature births and, consequently, neonatal and infant mortality.
ABSTRACT
OBJECTIVE: Pathological retinal neovascularization is vision-threatening. In mouse oxygen-induced retinopathy (OIR) we sought to define mitochondrial respiration changes longitudinally during hyperoxia-induced vessel loss and hypoxia-induced neovascularization, and to test interventions addressing those changes to prevent neovascularization. METHODS: OIR was induced in C57BL/6J mice and retinal vasculature was examined at maximum neovessel formation. We assessed total proteome changes and the ratio of mitochondrial to nuclear DNA copy numbers (mtDNA/nDNA) of OIR vs. control retinas, and mitochondrial oxygen consumption rates (OCR) in ex vivo OIR vs. control retinas (BaroFuse). Pyruvate vs. vehicle control was supplemented to OIR mice either prior to or during neovessel formation. RESULTS: In OIR vs. control retinas, global proteomics showed decreased retinal mitochondrial respiration at peak neovascularization. OCR and mtDNA/nDNA were also decreased at peak neovascularization suggesting impaired mitochondrial respiration. In vivo pyruvate administration during but not prior to neovessel formation (in line with mitochondrial activity time course) suppressed NV. CONCLUSIONS: Mitochondrial energetics were suppressed during retinal NV in OIR. Appropriately timed supplementation of pyruvate may be a novel approach in neovascular retinal diseases.
ABSTRACT
BACKGROUND: Ocular neovascular diseases, which contribute significantly to vision loss, lack effective preventive treatments. Recent studies have highlighted the significant involvement of immune cells in neovascular retinopathy. Myeloid-derived suppressor cells (MDSCs) promote the development of neovascularization, but it is unknown whether they participate in pathological neovascularization and whether they are expected to be a therapeutic target. METHOD: We investigated the role of MDSCs in promoting pathological angiogenesis using an oxygen-induced retinopathy (OIR) model, employing flow cytometry, immunofluorescence, and smart-seq analysis. Then, we evaluated the proportion of MDSCs in patient blood samples using flow cytometry. Additionally, we assessed the effect of MDSC depletion using an anti-Gr-1 monoclonal antibody on retinal vasculopathy and alterations in retinal microglia. RESULTS: In the OIR model, an elevated ratio of MDSCs was observed in both blood and retinal tissue during phase II (Neovascularization). The depletion of MDSCs resulted in reduced retinal neovascularization and vaso-obliteration, along with a decrease in microglia within the neovascularization area. Furthermore, analysis of gene transcripts associated with MDSCs indicated activation of vascular endothelial growth factor (VEGF) regulation and inflammation. Importantly, infants with ROP exhibited a higher proportion of MDSCs in their blood samples. CONCLUSION: Our results suggested that excessive MDSCs represent an unrecognized feature of ocular neovascular diseases and be responsible for the retinal vascular inflammation and angiogenesis, providing opportunities for new therapeutic approaches to ocular neovascular disease.