Clinical value of serum vitamin A and basic fibroblast growth factor levels in predicting retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical value of serum vitamin A(Vit A)and basic fibroblast growth factor(bFGF)levels predicting retinopathy of prematurity(ROP).METHODS: Prospective cohort studies. A total of 411 premature or low birth weight infants with gestational age less than 37 wk or birth weight less than 2 500 g who were delivered in Hainan Branch, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from January 2020 to December 2022 were selected as subjects. The Vit A and bFGF levels in peripheral blood were detected at 7 d and 35 d after birth, respectively.RESULTS: A total of 392 premature infants or low birth weight infants completed clinical study, including 51 cases in stage 1-2 ROP group, 23 cases in stage 3-5 ROP group and 318 cases in the group without ROP. At 7 d postnatal, the serum Vit A(0.44±0.17 μmol/L)and bFGF(0.53±0.16 ng/L)levels in stage 1-2 ROP group were lower than those in the group without ROP(0.50±0.12 μmol/L and 0.63±0.15 ng/L; all P<0.05). The serum Vit A(0.34±0.18 μmol/L)and bFGF(0.44±0.18 ng/L)levels in stage 3-5 ROP group were lower than those in the group without ROP(P<0.05). The serum Vit A and bFGF levels in stage 3-5 ROP group were lower than those in stage 1-2 ROP group(P<0.05). At 35d postnatal, the serum Vit A(0.33±0.19 μmol/L)and bFGF(0.39±0.19 ng/L)levels in stage 3-5 ROP group were lower than those in stage 1-2 ROP group(0.43±0.16 μmol/L and 0.48±0.17 ng/L; all P<0.05). According to the ROC curve drawn by serum Vit A, the AUC value was 0.853, the maximum Youden index was 0.68, the best sensitivity was 73%, and the best specificity was 95%. According to the ROC curve drawn by serum bFGF, the AUC value was 0.828, the maximum Youden index was 0.58, the best sensitivity was 90%, and the best specificity was 68%. According to the ROC curve drawn by serum Vit A combined with bFGF, the AUC value was 0.917, the maximum Youden index was 0.70, the best sensitivity was 70%, and the best specificity was 100%.CONCLUSION: Serum Vit A and bFGF levels are sensitive and effective indicators for predicting ROP. If the serum Vit A or bFGF levels are lower in premature infants or low birth weight infants, it may indicate the higher probability of ROP and its pathological stages. In addition, the clinica value of serum Vit A combined with bFGF in the diagnosis of ROP is higher than that of Vit A or bFGF alone, and the misdiagnosis rate is reduced.

Spatial patterns of prematurity and its determinants in the metropolitan region of São Paulo, Brazil, 2010-2019 / Padrões espaciais da prematuridade e seus determinantes na região metropolitana de São Paulo, Brasil, 2010-2019

ABSTRACT Objective: To analyze spatial distribution of preterm births and their association with maternal, social, and health services indicators in the metropolitan region of São Paulo, Brazil, 2010-2019. Methods: Ecological study using data on preterm newborns from 39 municipalities in the metropolitan region of São Paulo. Univariate global Moran's index (Im) was used to evaluate spatial association of prematurity, and univariate local Moran's index by using the cluster map (LISA) to identify spatial patterns and clusters. Bivariate global Moran's index was also used to analyze spatial autocorrelation with maternal, social, and health services indicators. Results: A total of 3,103,898 live births were registered in period 2010-2019, of which 331,174 (10.7%) were preterm. The global Moran's index showed spatial independence (Im=0.05; p-value=0.233) of the proportion of preterm births between municipalities. However, in the local spatial analysis it was possible to identify a statistically significant spatial cluster between the municipalities of Biritiba Mirim, Guararema and Salesópolis, with high proportions of preterm births. In the bivariate analysis, a significant positive spatial association was identified with proportions of mothers under 20 years old (Im=0.17; p-value=0.024) and mothers with low schooling (Im=0.17; p-value=0.020), and a significant negative spatial association with HDI (Im=-0.14; p-value=0.039). Conclusions: The local spatial approach identified a spatial cluster located in the far east of the metropolitan region of São Paulo, where actions by health managers are needed to minimize occurrence of preterm births.

RESUMO Objetivo: Analisar a distribuição espacial dos nascimentos prematuros e sua associação com indicadores maternos, sociais e de serviços de saúde na região metropolitana de São Paulo, Brasil, 2010-2019. Métodos: Estudo ecológico utilizando dados sobre recém-nascidos pré-termo dos 39 municípios da região metropolitana de São Paulo. Utilizou-se o índice de Moran (Im) global univariado para avaliar a associação espacial da prematuridade, e o índice de Moran local univariado por meio do mapa de clusters (LISA) para a identificação de padrões e aglomerados espaciais. Também foi utilizado o índice de Moran global bivariado para analisar a autocorrelação espacial com os indicadores maternos, sociais e de serviços de saúde. Resultados: Foram registrados 3.103.898 nascidos vivos no período 2010-2019, dos quais 331.174 (10,7%) foram prematuros. O índice de Moran global mostrou independência espacial (Im=0,05; p-valor=0,233) da proporção dos nascimentos prematuros entre municípios. No entanto, na análise espacial local foi possível identificar aglomerado espacial estatisticamente significativo entre os municípios de Biritiba Mirim, Guararema e Salesópolis, com proporções altas de nascimentos pré-termo. Na análise bivariada, identificou-se associação espacial significativa positiva com proporções de mães menores de 20 anos (Im=0,17; p-valor=0,024) e mães com baixa escolaridade (Im=0,17; p-valor=0,020), e associação espacial significativa negativa com IDH (Im=-0,14; p-valor=0,039). Conclusão: A abordagem espacial local identificou agrupamento espacial situado no extremo leste da região metropolitana de São Paulo, onde ações dos gestores de saúde são necessárias para minimizar a ocorrência de partos prematuros.

Lesión pulmonar aguda producida por transfusión (TRALI): Reporte de caso

Introducción: La lesión pulmonar aguda (TRALI) y la sobrecarga circulatoria (TACO) son las principales causas de morbilidad y mortalidad relacionadas con la transfusión. La TRALI se presenta durante o después de las transfusiones de plasma y sus derivados, o por inmunoglobulinas en alta concentración intravenosa; se asocia a procesos sépticos, cirugías y transfusiones masivas. La TACO es la exacerbación de manifestaciones respiratorias en las primeras 6 horas postransfusión. Reporte caso: Paciente de sexo masculino de 38 días de vida, ingresó al servicio de urgencias con un cuadro clínico de 8 días de evolución, caracterizado por dificultad respiratoria dado por retracciones subcostales y aleteo nasal sin otro síntoma asociado, con antecedentes de importancia de prematuridad y bajo peso al nacer. El reporte de hemograma arrojó cifras compatibles con anemia severa, por lo que requirió transfusión de glóbulos rojos empaquetados desleucocitados. El paciente presentó un cuadro respiratorio alterado en un periodo menor a 6 horas, por lo que se descartaron causas infecciosas y finalmente se consideró cuadro compatible con TRALI. Conclusiones: Se debe considerar una lesión pulmonar aguda relacionada con una transfusión de sangre si se produce una insuficiencia respiratoria aguda durante o inmediatamente después de la infusión de hemoderivados que contienen plasma.

Introduction: Acute lung injury (TRALI) and circulatory overload (TACO) are the main causes of transfusion-related morbidity and mortality. TRALI occurs during or after transfusions of plasma or its derivatives, or by immunoglobulins in high intravenous concentration; it is associated with septic processes, surgeries, and massive transfusions. TACO is the exacerbation of respiratory manifestations in the first 6 hours post transfusion. Case report: A 38-day-old male was admitted to the emergency department with clinical symptoms experienced over the course of 8 days and characterized by respiratory distress due to subcostal retractions and nasal flaring with no other associated symptoms. Important antecedents included prematurity and low birth weight. The hemogram report showed figures compatible with anemia, which benefited from transfusion of packed red blood cells without leukocytes. In a period of less than 6 hours, the patient presented altered respiratory symptoms, practitioners ruled out infectious causes and finally considered clinical signs compatible with TRALI. Conclusion: Acute lung injury related to blood transfusion should be considered if acute respiratory failure occurs during or immediately after infusion of plasma-containing blood products.

Complicaciones neurológicas de la prematuridad / Neurological consequences of prematurity

Resumen Los nacimientos prematuros representan un in dicador importante de salud de un país. Estos niños tienen un mayor riesgo de mortalidad y morbilidad. Las principales lesiones encefálicas en los prematuros incluyen lesiones de la sustancia blanca, hemorragias intracraneanas y lesiones cerebelosas, que pueden ser detectadas mediante ecografía encefálica y resonancia magnética, siendo esta última la técnica más sensible. Estas lesiones pueden tener repercusión a largo plazo en el neurodesarrollo de los prematuros, con un mayor riesgo de parálisis cerebral, trastornos cognitivos, con ductuales, sensoriales y del aprendizaje, entre otros. Es fundamental aplicar estrategias de prevención y aten ción temprana para reducir las consecuencias negativas de las lesiones encefálicas asociadas a la prematuridad.

Abstract Premature births are an important health indicator for a country. These children have a higher risk of mor tality and morbidity. The main brain injuries in preterm infants include white matter injuries, intracranial hem orrhages, and cerebellar injuries. These injuries can be detected through brain ultrasound and magnetic reso nance imaging (MRI), with MRI being the most sensitive technique. Perinatal brain injuries may have long-term consequences on the neurodevelopment of preterm infants, with an increased risk of cerebral palsy, cogni tive, behavioral, sensory, and learning disorders, among others. It is key to implement prevention strategies and early intervention to reduce the negative consequences of brain injuries associated with prematurity.

Fetal hemoglobin, blood transfusion, and retinopathy of prematurity in preterm infants: An observational, prospective study

Purpose: The objective of this study was to identify the association between fetal hemoglobin (HbF) concentration, blood transfusion, and retinopathy of prematurity (ROP) in preterm infants. Methods: This was an observational, prospective study. A total of 410 preterm infants born with <36 weeks gestational age and <2.0 kg birth weight in a tertiary care center of central India for a period of 1 year were included in this study. Clinical data were obtained from case notes. HbF of infants was measured in the blood sample using high?performance liquid chromatography at the first visit and after 1 month follow?up and was analyzed statistically. Dilated fundus examination was done as per ROP screening guidelines, and ROP was classified as per the International Classification of Retinopathy of Prematurity (ICROP), 2021. The study subjects were divided into two groups based on the status of ROP. The relationship among HbF, blood transfusion, and ROP was evaluated in both the groups. The relationship between other clinical characteristics and various neonatal risk factors was also studied between the groups. Results: A total of 410 preterm infants were included in this study, of which 110 infants had ROP (26.8%). Blood transfusion was found to be significantly associated with the development of ROP. Higher fraction of HbF (%) was associated with a lower prevalence of ROP. HbF was also inversely related with the severity of ROP. Conclusion: Replacing HbF by adult hemoglobin during blood transfusion may promote the development of ROP. Conversely, maintaining a higher percentage of HbF may be a protective factor against ROP.

Risk factors of acute kidney injury in very low birth weight infants in a tertiary neonatal intensive care unit

Abstract Objective Acute kidney injury (AKI) in the neonatal period is associated with worst outcomes as increased mortality and increased length of hospital stay. Very low birth weight (VLBW) newborns are at higher risk for developing several other conditions that are associated with worst outcomes. Understanding the risk factors for AKI may help to prevent this condition and improve neonatal care for this population. Methods This retrospective cohort study included 155 very low birth weight newborns admitted between 2015 and 2017. The authors compared the newborns who developed neonatal AKI with the non-AKI group and analyzed the main risk factors for developing AKI in the population. The authors also performed an analysis of the main outcomes defined as the duration of mechanical ventilation, length of stay, and death. Results From the cohort, a total of 61 (39.4%) patients had AKI. The main risk factors associated with Neonatal AKI were necrotizing enterocolitis (aOR 7.61 [1.69 - 34.37]; p = 0.008), neonatal sepsis (aOR 2.91 [1.17 - 7.24], p = 0.021), and hemodynamic instability (aOR 2.99 [1.35 - 6.64]; p = 0.007). Neonatal AKI was also associated with an increase in the duration of mechanical ventilation in 9.4 days (p = 0.026) and in an increase in mortality 4 times (p = 0.009), after adjusting for the other variables. Conclusion The present results highlight the importance of minimizing sepsis and necrotizing enterocolitis, as well as the importance of identifying hemodynamic instability, to prevent AKI and diminish the burden of morbimortality in VLBW newborns.

Validation of three weight gain-based algorithms as a screening tool to detect retinopathy of prematurity: A multicenter study

Purpose: Screening guidelines for retinopathy of prematurity (ROP) are updated frequently to help clinicians identify infants at risk of type 1 ROP. This study aims to evaluate the accuracy of three different predictive algorithms—WINROP, ROPScore, and CO?ROP—in detecting ROP in preterm infants in a developing country. Methods: This retrospective study was conducted on 386 preterm infants from two centers between 2015 and 2021. Neonates with gestational age ?30 weeks and/or birth weight ?1500 g who underwent ROP screening were included. Results: One hundred twenty?three neonates (31.9%) developed ROP. The sensitivity to identify type 1 ROP was as follows: WINROP, 100%; ROPScore, 100%; and CO?ROP, 92.3%. The specificity was 28% for WINROP, 1.4% for ROPScore, and 19.3% for CO?ROP. CO?ROP missed two neonates with type 1 ROP. WINROP provided the best performance for type 1 ROP with an area under the curve score at 0.61. Conclusion: The sensitivity was at 100% for WINROP and ROPScore for type 1 ROP; however, specificity was quite low for both algorithms. Highly specific algorithms tailored to our population may serve as a useful adjunctive tool to detect preterm infants at risk of sight?threatening ROP

Demographics and Clinical Patterns of Retinopathy of Prematurity at the University of Teaching Hospitals, Women and Newborn Hospital

Background: Retinopathy of prematurity (ROP) is a disorder of the developing retina of very low birth weight (VLBW) preterm infants. It is an important cause of childhood blindness and is listed as one of the causes of avoidable blindness in the vision 2020 - “The Right to Sight” Programme.ROP is more prevalent in highly developed countries where neonatal services’ availability, access and outcomes are good. The survival rates of Very low Birth Weight (VLBW) infant and low gestational age (GA) at the University Teaching Hospital (UTH), Women and Newborn Hospital (WNH) Neonatal Intensive Care Unit has improved.Aims: To estimate the prevalence of ROP at UTH, WNH, NICU.Study Design: Hospital-based cross-sectional study.Place and Duration: Neonatal Intensive Care Unit, Women and Newborn hospital at the University Teaching Hospital, in Lusaka, Zambia between November 2021 to April 2022.Methodology: We included 110 (54.5% males and 45.5% females) infants either born at <32 weeks GA or weighed <1500g. Dilated fundus examinations were done at 4 to 6 weeks chronological age or 31 to 33 weeks GA. Medical records were reviewed to identify associated factors.Results: Mean gestational age at birth was 30.6±2 weeks ranging from 27 to 34 weeks, mean birth weight was 1422.7±334.3 g ranging from 900g to 2200 g, mean Apgar score at 1 minute was 7±1.3, at 5 minutes the mean was 7.8±0.9, and at 10 minutes the mean was 8.4±0.7. Twenty-six (23.6%) were products of multiple gestations. Hyaline membrane disease was observed in 14 (12.7%), neonatal sepsis in 48 (43.6%), necrotising enterocolitis in 6 (5.5%), patent ductus arteriosus in one (0.9%), and hyperglycaemia in 56 (50.9%) cases.Conclusion: Our study found no participant with retinopathy of prematurity at UTH NICU. Further, the study could not make associations between suggested risk factors to the development of ROP. However, being a novel study on this topic in the country, it highlights the importance of setting up screening protocols and their attendant equipment in Special Care Baby Units at UTH and improving neonatal care services.

Factores de riesgo asociados a falla en la extubación en pacientes prematuros en la unidad de cuidados intensivos neonatales / Risk factors associated with extubation failure in premature patients in the neonatal intensive care unit

Resumen Antecedentes: En la unidad de cuidados intensivos neonatales el 47% de prematuros requieren ventilación mecánica (VM), cuyo uso prolongado se asocia con secuelas a largo plazo. Objetivo: Identificar los factores de riesgo para falla en la extubación en prematuros. Material y métodos: Estudio de casos y controles; se tomó como casos las extubaciones fallidas (EF) y como controles las extubaciones exitosas (EE). El fracaso de la extubación se definió como la reintubación dentro de las primeras 72 horas. Resultados: El 46% de prematuros ingresados requirió VM. Se presentaron 12 EF y 27 EE. La proporción de EF fue del 31%. La VM más de 7 días fue del 17% en los casos y del 11% en los controles (OR: 0.6; IC 95%: 0.09-4.32; p = 0.634). La principal causa de reintubación fue por apnea (50%). Conclusiones: Los parámetros establecidos para este estudio no se determinaron como factores de riesgo para extubación fallida. Debido a los números de casos en este estudio, no podemos identificar un buen valor de corte para los factores de riesgo y predictores. Se requieren más estudios a gran escala para confirmar nuestros hallazgos y determinar los valores de corte.

Abstract Background: In the neonatal intensive care unit, 47% of premature infants require mechanical ventilation (MV); its prolonged use is associated with long-term sequelae. Objective: To identify the risk factors for extubation failure in premature infants. Material and methods: Case-control study, taking failed extubations (FE) as cases and successful extubations (SE) as controls. Extubation failure was defined as reintubation within the first 72 hours. Results: 46% of hospitalized premature infants required MV; twelve FE and 27 SE were presented. The proportion of FE was 31%. MV over 7 days was 17% in cases and 11% in controls (OR: 0.6; 95% CI: 0.09-4.32; p = 0.634). The main cause of reintubation was apnea (50%). Conclusions: The parameters established for this study were not determined as risk factors for failed extubation. Due to the case numbers in this study, we are unable to identify a good cut-off value for risk factors and predictors. More large-scale studies are required to confirm our findings and determine cut-off values.

"É um bombardeio de sentimentos": experiências maternas no contexto do nascimento prematuro / "It's an explosion of feelings": maternal experiences in the context of preterm birth / "Es un bombardeo de sentimientos": experiencias maternas en el contexto del parto prematuro

O presente estudo investigou a experiência da maternidade de mães de bebês nascidos extremamente prematuros durante suas hospitalizações na UTI Neo. Em particular, buscou-se conhecer os sentimentos maternos relacionados a esse contexto. Participaram 18 mães cujos bebês tinham entre 25 e 28 semanas gestacionais e pesavam entre 625g e 1000g. As mães foram entrevistas 15 dias após o parto e as respostas foram examinadas por meio de análise de conteúdo qualitativa. Foram desenvolvidos três eixos, derivados das entrevistas: sentimentos sobre a UTI Neo; sentimentos sobre as manifestações do bebê; e sentimentos sobre a maternidade. Os achados revelaram uma complexidade de sentimentos maternos no contexto da UTI Neo. Porém, destacaram-se nas verbalizações maternas o investimento narcísico das mães nos seus bebês, que as levavam a se comunicar com eles a partir de pequenos gestos e expressões sensoriais, o que oportunizava, simultaneamente, a construção de um lugar simbólico para o bebê. (AU)

The present study investigated the motherhood experience of mothers of extremely preterm infants during their hospitalizations in the NICU. In particular, we sought to investigate the maternal feelings related to this context. Participants included 18 mothers whose babies were between 25 and 28 gestational weeks and weighed between 625g and 1000g. Mothers were interviewed 15 days after delivery and the responses were examined using qualitative content analysis. Three axes were developed, derived from the interviews: feelings about the NICU; feelings about the baby's manifestations; and feelings about motherhood. The findings revealed the complexity of maternal feelings in the context of the NICU. However, the mothers' narcissistic investment in their babies, which led them to communicate with them using small gestures and sensory expressions, stood out in the maternal verbalizations, which simultaneously made it possible to build a symbolic place for the infant. (AU)

El presente estudio investigó la experiencia de maternidad de madres de bebés nacidos extremadamente prematuros durante sus hospitalizaciones en la UCI Neonatal. En particular, se buscó conocer los sentimientos maternos relacionados con este contexto. Participaron 18 madres cuyos bebés tenían entre 25 y 28 semanas de gestación y pesaban entre 625 g y 1000 g. Las madres fueron entrevistadas 15 días después del parto y las respuestas se examinaron mediante análisis de contenido cualitativo. Se desarrollaron tres ejes, derivados de las entrevistas: sentimientos sobre la UCI Neonatal; sentimientos sobre las manifestaciones del bebé; y sentimientos sobre la maternidad. Los hallazgos revelaron una complejidad de los sentimientos maternos en el contexto de la UCI Neonatal. Sin embargo, la inversión narcisista de las madres en sus bebés se evidenció en sus verbalizaciones, que las llevaba a comunicarse con ellos a través de pequeños gestos y expresiones sensoriales que, simultáneamente, permitían la construcción de un lugar simbólico para el bebé. (AU)

Study to evaluate the relation between weight gain in infants and occurrence of retinopathy of prematurity

Purpose: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Capturing serial daily postnatal weight gain can act as an innovative, low?cost method of risk stratification. We aim to study the relation between weight gain in infants and occurrence of ROP. Methods: The prospective, observational study was conducted on 62 infants. ROP screening was done based on the Rashtriya Bal Swasthya Karyakram (RBSK) criteria. Infants were classified into no ROP (n = 28), mild ROP (n = 8), and treatable ROP (n = 26) groups. Average daily postnatal weight gain was measured and its relation to development of ROP was studied. All statistical calculations were done using Statistical Package for the Social Sciences (SPSS) 21 version (SPSS Inc., Chicago, IL, USA) statistical program for Microsoft Windows. Results: Mean rate of weight gain in no ROP group, mild ROP group, and treatable ROP group was 33.12, 27.19, and 15.31 g/day, respectively (P = 0.001). Mean gestational age and birth weight in treatable group (n = 26) were 31.38 weeks and 1572.31 g, respectively. Receiver operating curve analysis revealed a cutoff of 29.33 g/day for ROP and 21.91 g/day for severe ROP. Conclusion: We concluded that, babies with poor weight gain of below 29.33 g/day are at high risk for ROP and babies with wight gain of 21.91 g/day are at high risk for severe ROP. These babies should be followed meticulously. So, the rate of weight gain of a preterm can help us to prioritize babies.

Retinopathy of prematurity in preterm infants born following assisted conception versus spontaneously conceived pregnancies – A 2-year retrospective observational study from an urban tertiary eye care referral center in South India

Purpose: The aim of this study is to determine if in vitro fertilization (IVF) is associated with an increase in the incidence of retinopathy of prematurity (ROP) among preterm infants. Methods: This retrospective, comparative study included all the preterm babies who were screened under an urban multicentric outreach project between April 2019 and August 2022. Infant details including gender, birth weight, mode of conception, single or multiple gestation, gestational age and post?menstrual age in weeks, age at presentation, and any presence of risk factors were recorded and analyzed. Results: Among 444 preterm babies included in the study, 373 (84%) were conceived normally and 71 (16%) were conceived by IVF. ROP was found in 99 (22.29%) babies in total. There was no significant difference in the incidence of any stage of ROP between the two groups; however, higher stages of ROP were found to be relatively more frequent in the spontaneous conception group in our study. We also found a statistically significant difference in the presence of ROP among singletons, twins, and triplets. Conclusion: IVF was found not to independently increase the risk of ROP in preterm infants. More prospective studies and randomized controlled trials are needed to establish the relationship between the mode of conception and development of severe ROP in preterm infants

Efficacy of a biosimilar ranibizumab monotherapy for the treatment of retinopathy of prematurity

Purpose: To evaluate the efficacy of a biosimilar ranibizumab (Razumab) on outcomes of retinopathy of prematurity (ROP) for the first time. Methods: This retrospective study included infants presenting with stage 3+ ROP either in zone 1 or zone 2 posterior or aggressive posterior ROP (APROP). All eligible infants received intravitreal razumab (0.25 mg/0.025 ml) monotherapy. Follow?up was continued monthly till complete retinal vascularization was achieved while retreatment with razumab was given when recurrent neovascularization was noted. In case of no recurrence but incomplete vascularization, laser photocoagulation was done to the residual avascular retina. Results: We included 118 eyes of 59 infants with a median gestational age of 30 weeks and median birth weight of 1250 grams. At presentation, APROP was found in 28 eyes (24%) of 14 babies while stage 3 disease was seen in zone 1 in another 28 eyes (24%) and the remaining 62 eyes (52%) had stage 3 ROP in zone 2 posterior region. Complete resolution of ROP along with complete vascularization was seen in 22 eyes (19%) at a median of 55 days (IQR = 31–56 days) and 42 eyes (35%) showed a recurrent neovascularization at a median of 51 days post razumab (IQR = 42– 55 days). The cumulative incidence of recurrence of neovascularization (21%, 95% CI = 14%–29%) peaked at seven weeks and was significantly higher in eyes with APROP (43%, 95% CI = 27%–63%) compared to eyes without APROP (13.4%, 95%CI, 8%?22%) (P < 0.001). Conclusion: Razumab appears to be safe and effective in treating ROP, with about a third requiring reinjection at seven weeks after the first dose.

Comparison between Protocols for Management of Fetal Growth Restriction / Comparação entre protocolos de acompanhamento da restrição de crescimento fetal

Abstract This comprehensive review compares clinical protocols of important entities regarding the management of fetal growth restriction (FGR), published since 2015. Five protocols were chosen for data extraction. There were no relevant differences regarding the diagnosis and classification of FGR between the protocols. In general, all protocols suggest that the assessment of fetal vitality must be performed in a multimodally, associating biophysical parameters (such as cardiotocography and fetal biophysical profile) with the Doppler velocimetry parameters of the umbilical artery, middle cerebral artery, and ductus venosus. All protocols reinforce that the more severe the fetal condition, the more frequent this assessment should be made. The timely gestational age and mode of delivery to terminate the pregnancy in these cases can vary much between the protocols. Therefore, this paper presents, in a didactic way, the particularities of different protocols for monitoring FGR, in order to help obstetricians to better manage the cases.

Resumo Esta revisão compreensiva compara protocolos clínicos de entidades importantes em relação ao manejo da restrição de crescimento fetal (RCF), publicados desde 2015. Cinco protocolos foram escolhidos para a extração de dados. Não houve diferenças relevantes quanto ao diagnóstico e classificação da RCF entre os protocolos. Em geral, todos os protocolos sugerem que a avaliação da vitalidade fetal deve ser realizada de forma multimodal, associando parâmetros biofísicos (como cardiotocografia e perfil biofísico fetal) aos parâmetros dopplervelocimétricos da artéria umbilical, artéria cerebral média e ducto venoso. Todos os protocolos reforçam que quanto mais grave a condição fetal, mais frequente essa avaliação deve ser feita. A idade gestacional oportuna e o modo de parto para interromper a gravidez nesses casos podem variar muito entre os protocolos. Portanto, este trabalho apresenta, de forma didática, as particularidades de diferentes protocolos de acompanhamento de RCF, a fim de auxiliar os obstetras no melhor manejo dos casos.

Role of the NF-kB/parkin/vegfr-1 pathway associated with hypoxic-ischemic insult in germinal matrix samples of newborn infants / O papel da via NF-kB/parkin/vegfr-1 associada à agressão hipóxico-isquêmica em amostras de matriz germinativa de pacientes recém-nascidos

Abstract Objective: Given the high proliferative activity of germinal matrix and its direct correlation with hypoxemia, it is necessary to investigate the possible molecular regulation pathways, to understand the existing clinical relationship between the hypoxic-ischemic insult and the biomarkers NF-kB, AKT-3, Parkin, TRK-C and VEGFR-1. Methods: A hundred and eighteen germinal matrix samples of the central nervous system of patients who died in the first 28 days of life were submitted to histological and immunohistochemistry analysis to identify the tissue immunoexpression of those biomarkers related to asphyxia, prematurity, and death events within 24h. Results: A significantly increased tissue immunoexpression of NF-kB, AKT-3 and Parkin was observed in the germinal matrix of preterm infants. In addition, significantly decreased tissue immunoexpression of VEGFR-1 and NF-kB was observed in patients who experienced asphyxia followed by death within 24 hours. Conclusions: The results suggest a direct involvement between the hypoxic-ischemic insult and NF-kB and VEGFR-1 markers since a decreased immunoexpression of these biomarkers was observed in asphyxiated patients. Furthermore, it is suggested that there was not enough time for VEGFR-1 to be transcribed, translated and expressed on the surface of the plasma membrane. This temporality can be observed in the relationship between NF-kB expression and the survival time of individuals who died within 24 hours, suggesting that this factor is essential for the production of VEGFR-1 and, therefore, to carry out the necessary remodeling effect to neovascularize the affected region.

RESUMO Objetivo: Dada a alta atividade proliferativa da matriz germinativa e sua correlação direta com a hipoxemia, é necessário investigar as possíveis vias de regulação molecular para entender a relação clínica existente entre o insulto hipóxico-isquêmico e os biomarcadores NF-kB, AKT -3, Parkina, TRK-C e VEGFR-1. Métodos: Cento e dezoito amostras de matriz germinativa do sistema nervoso central de pacientes que faleceram nos primeiros 28 dias de vida foram submetidas a análise histológica e imuno-histoquímica para identificar a imunoexpressão tecidual desses biomarcadores relacionados a eventos de asfixia, prematuridade e óbito em 24 horas. Resultados: Observou-se uma imunoexpressão tecidual significativamente aumentada de NF-kB, AKT-3 e Parkin na matriz germinativa de prematuros. Além disso, constatou-se uma imunoexpressão tecidual significativamente diminuída de VEGFR-1 e de NF-kB em pacientes que apresentaram asfixia seguida de morte em 24 horas. Conclusões: Os resultados sugerem o envolvimento direto entre o insulto hipóxico-isquêmico e os marcadores NF-kB e VEGFR-1, visto que se observou uma imunoexpressão diminuída destes biomarcadores nos pacientes asfixiados. Além disso, sugere-se que não houve tempo suficiente para que o VEGFR-1 fosse transcrito, traduzido e expresso na superfície da membrana plasmática. Essa temporalidade pode ser observada na relação entre a expressão de NF-kB e o tempo de vida dos indivíduos que morreram em 24 horas, o que sugere que esse fator é essencial para a produção do VEGFR-1 e, portanto, para realizar o efeito remodelador necessário para neovascularizar a região afetada.

Fatores de risco pré-natais e perinatais de mães que tiveram partos prematuros / Prenatal and perinatal risk factors of mothers who had preterm births / Factores de riesgo prenatales y perinatales de madres que tuvieron partos prematuros

Objetivo: caracterizar a prevalência dos fatores de risco maternos, pré-natais e perinatais, bem como o suporte familiar recebido pela mãe durante a gestação, e verificar se estes estão ou não associados aos nascimentos prematuros. Método: Trata-se de um estudo transversal, quantitativo e retrospectivo, realizado em uma universidade do Distrito Federal. As coletas de dados foram realizadas em 2021 e 2022 por meio de questionários aplicados a 22 mães de bebês prematuros que atenderam aos seguintes critérios: terem dado à luz a bebês nascidos com 37 semanas ou menos e terem concordado voluntariamente em responder ao questionário. Resultados: Foi observada uma prevalência de mães com idade entre 18 e 29 anos (50%), pardas (54,54%), sem histórico de parto prematuro anterior (72,80%), com gestação única (81,81%), realizando entre 7 e 10 consultas pré-natais (45,40%), sem realizar fisioterapia pélvica (86,36%) ou exercícios físicos durante a gestação (86,36%). De acordo com a escala Apgar familiar, essas mães possuem uma família altamente funcional (81,81%). Conclusão: Os dados analisados indicam que as mães avaliadas têm uma família funcional e recebem um suporte familiar adequado. No entanto, algumas variáveis maternas, como etnia, tipo de gravidez, idade, prática de exercícios físicos e realização de fisioterapia pélvica, podem ter influência no nascimento de bebês prematuros.

Objective: to characterize the prevalence of maternal, prenatal, and perinatal risk factors, as well as family support received during pregnancy, and investigate their association with premature births. Method: This cross- sectional, quantitative, and retrospective study was conducted at a university in the Federal District. Data was collected in 2021 and 2022 through a questionnaire administered to 22 mothers of preterm infants who met the following criteria: being mothers of babies born at 37 weeks or less and voluntarily agreeing to respond to the questionnaire. Results: The majority of the mothers were aged between 18 and 29 years (50%), were of brown ethnicity (54.54%), had no history of previous premature birth (72.80%), had a single pregnancy (81.81%), had 7 to 10 prenatal consultations (45.40%), did not undergo pelvic physiotherapy (86.36%), or participate in physical exercises during pregnancy (86.36%). According to the family Apgar scale, these mothers had highly functional families (81.81%). Conclusion: The analyzed data indicate that the evaluated mothers have functional families with adequate family support. However, certain maternal variables, such as ethnicity, type of pregnancy, age, and practice of physical exercises, may influence the risk of preterm birth.

Objetivo: caracterizar la prevalencia de factores de riesgo maternos, prenatales y perinatales, y el apoyo familiar recibido durante el embarazo, e investigar su asociación con los partos prematuros. Método: Este estudio transversal, cuantitativo y retrospectivo se llevó a cabo en una universidad del Distrito Federal. Se recopiló información en 2021 y 2022 mediante un cuestionario administrado a 22 madres de bebés prematuros que cumplían con los siguientes criterios: ser madres de bebés nacidos a las 37 semanas de gestación o menos y estar dispuestas a responder voluntariamente el cuestionario. Resultados: Predominaron las madres de 18 a 29 años (50%), mestizas (54,54%), sin antecedentes de parto prematuro previo (72,80%), con embarazo único (81,81%), con 7 a 10 consultas prenatales (45,40%), que no recibieron fisioterapia pélvica (86,36%), ni realizaron ejercicios físicos durante el embarazo (86,36%). Según la escala de Apgar familiar, estas madres tenían familias altamente funcionales (81,81%). Conclusión: Los datos analizados indican que las madres evaluadas tienen familias funcionales y apoyo familiar adecuado. Sin embargo, ciertas variables maternas, como la etnia, el tipo de embarazo, la edad y la práctica de ejercicios físicos o la fisioterapia pélvica pueden influir en el riesgo de parto prematuro

Clinical analysis and curative effect of reactivation of retinopathy of prematurity after intravitreous injection of ranibizumab / 中华眼底病杂志

Objective:To observe the clinical characteristics and therapeutic effect of reactivation of retinopathy of prematurity (ROP) patients after intravitreal injection of ranibizumab (IVR).Methods:A retrospective case series study. Eleven children with ROP (21 eyes) who were reactivated after IVR in Shenzhen Eye Hospital from January 2019 to October 2021 were included in the study. Among them, there were 6 males (11 eyes) and 5 females (10 eyes), with the gestational age of (27.6±2.2) weeks and birth weight of (1 034.6±306.5) g. At the first IVR treatment, 14 eyes (63.7%, 14/22) had acute ROP (AROP), 8 eyes (36.3%, 8/22) had threshold lesions. Post-reactivation treatments include IVR, retinal laser photocoagulation (LP), or minimally invasive vitrectomy (MIVS). The follow-up time after treatment was 12 to 18 months. Birth gestational age, birth weight, treatment method, corrected gestational age at treatment, lesion stage before and after treatment, lesion reactivation and regression time were recorded. The clinical characteristics and efficacy were observed and analyzed.Results:The time from initial IVR treatment to reactivation was (8.2±3.5) weeks. The corrected gestational age of the child was (43.62±4.08) weeks. In 21 eyes, AROP, threshold lesion, prethreshold lesion, and stage 4 lesion were in 2, 4, 12, and 3 eyes, respectively. The patients were treated with IVR, LP, IVR+LP, IVR+MIVS in 2, 13, 4 and 2 eyes, respectively. After the first reactivation treatment, the time of regression and stability was (8.4±4.9) weeks after treatment. There were 5 eyes with secondary reactivation of the lesion, and the lesion stages were stage 3, stage 4a and stage 5 in 2, 1 and 2 eyes, respectively. The mean reactivation time was (19.3±6.0) weeks after the last treatment. The patients in stage 3, stage 4a and stage 5 were treated with LP, LP+MIVS and IVR, respecitively, and the lesions subsided steadily during follow-up. At the last follow-up, 19 out of 21 eyes showed complete regression of the lesions, stable photocoagulation, regression of crista-like lesions, no additional lesions, and retinal leveling. All retinal detachment was "funnel-shaped" in 2 eyes.Conclusions:The lesion reactivation of AROP after IVR treatment is more common. The early reactivation rate is higher after treatment. There is a possibility of reactivation twice after re-treatment.

Clinical characteristics and effect of anti-vascular endothelial growth factor therapy in retinopathy of prematurity in Sichuan province / 中华眼底病杂志

Objective:To analyze the clinical characteristics and evaluate the effect and safety of anti-vascular endothelial growth factor (VEGF) therapy in retinopathy of prematurity (ROP) in Sichuan province.Methods:A retrospective study. From January 2013 to January 2022, 156 patients (306 eyes) with ROP who received intravitreal anti-VEGF therapy for the first time in the Department of Ophthalmology, West China Hospital of Sichuan University were selected. According to the type of anti-VEGF drugs, the children were divided into intravitreal injection of ranibizumab (IVR) group and intravitreal injection of conbercept (IVC) group; IVC group was divided into hospital group and referral group according to the different paths of patients. After treatment, the patients were followed up until the disease degenerated (vascular degeneration or complete retinal vascularization) or were hospitalized again for at least 6 months. If the disease recurred or progressed, the patients were re-admitted to the hospital and received anti-VEGF drug treatment, laser treatment or surgical treatment according to the severity of the disease. Clinical data of these children was collected, including general clinical characteristics: gender, gestational age at birth (GA), birth weight (BW), history of oxygen inhalation; pathological condition: ROP stage, zone, whether there were plus lesions; treatment: treatment time, postmenstrual gestational age at the time of the first anti-VEGF drug treatment; prognosis: re-treat or not, time of re-treatment, mode of re-treatment; adverse events: corneal edema, lens opacity, endophthalmitis, retinal injury, and treatment-related systemic adverse reactions. The measurement data between groups were compared by t test, and the count data were compared by χ2 test or rank sum test. Results:Of the 306 eyes of 156 children with ROP, 74 were male (47.44%, 74/156) and 82 were female (52.56%, 82/156). Each included child had a history of oxygen inhalation at birth. The GA was (28.43±2.19) (23.86-36.57) weeks, BW was (1 129±335) (510-2 600) g, and the postmenstrual gestational age was (39.80±3.04) (31.71-49.71) weeks at the time of the first anti-VEGF drug treatment. All patients were diagnosed as type 1 ROP, including 26 eyes (8.50%, 26/306) of aggressive ROP (A-ROP), 39 eyes (12.74%, 39/306) of zone Ⅰ lesions, and 241 eyes (78.76%, 241/306) of zone Ⅱ lesions. The children were treated with intravitreal injection of anti-VEGF drugs within 72 hours after diagnosis. Among them, 134 eyes (43.79%, 134/306) of 68 patients were treated with IVR, and 172 eyes (56.21%, 172/306) of 88 patients were treated with IVC. In IVC group, 67 eyes of 34 patients (38.95%, 67/172) were in the hospital group and 105 eyes of 54 patients (61.05%, 105/172) were in the referral group. 279 eyes (91.18%, 279/306) were improved after one treatment, 15 eyes (4.90%, 15/306) were improved after two treatments, and 12 eyes (3.92%, 12/306) were improved after three treatments. The one-time cure rate of IVR group was lower than that of IVC group, but the difference was not statistically significant ( χ2=1.665, P=0.197). In different ROP categories, IVC showed better therapeutic effect in A-ROP, and its one-time cure rate was higher than that in IVR group, with statistically significant difference ( χ2=7.797, P<0.05). In the hospital group of IVC group, the GA, BW and the postmenstrual gestational age at first time of anti-VEGF drug treatment were lower than those in the referral group, and the difference was statistically significant ( t=-2.485, -2.940, -3.796; P<0.05). The one-time cure rate of the hospital group and the referral group were 94.94%, 92.38%, respectively. The one-time cure rate of the hospital group was slightly higher than that of the referral group, but the difference was not statistically significant ( χ2=0.171, P=0.679). In this study, there were no ocular and systemic adverse reactions related to drug or intravitreal injection in children after treatment. Conclusions:Compared with the characteristics of ROP in developed countries, the GA, BW and postmenstrual gestational age of the children in Sichuan province are higher. Both IVR and IVC can treat ROP safely and effectively. There is no significant difference between the two drugs in the overall one-time cure effect of ROP, but IVC performed better in the treatment of A-ROP in this study.

Vascularization of intravitreal injection of Conbercept in the treatment of retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate retinal vascularization caused by the intravitreal injection of Conbercept in the treatment of a series of retinopathy of prematurity(ROP)cases in Type Ⅰ(threshold and pre-threshold period)and aggressive ROP(A-ROP).METHODS: The data of 34 ROP cases(67 eyes)treated by intravitreal injection of Conbercept(IVC)in the ophthalmology department of the Xiamen Children's Hospital from July 2017 to March 2020 were retrospectively analyzed. Reactivation, which refers to recurrence of acute phase features, occurred at any stage of the disease in the presence or absence of other diseases. RESULT: The average gestational age of the 34 children was 28.82±2.32wk. The average birth weight was 1155.18±398.22g. The lesion zone of 19 cases(37 eyes)was Zone Ⅰ. In 10 cases(20 eyes), the lesion was in Zone Ⅱ, and in 5 cases(10 eyes), the lesion was in the posterior Zone Ⅱ. The total effective rate of disease control in ROP children treated with once IVC was 73.1%(49/67), and the vascularization of Zone Ⅱ was completed. The patients showed variable changes in the vascularization in Zone Ⅲ. For the patients who received one treatment and did not reactivate, the average rate of Type Ⅰ vascularization of ROP was 9.11±2.49wk, and the A-ROP was 13.40±4.04wk. The rate of A-ROP vascularization in Zone Ⅱ was significantly longer compared to Type Ⅰ.CONCLUSION: IVC effectively completes vascularization in Zone Ⅱ.

Progress of anti-vascular endothelial growth factor drugs for the treatment of retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

Retinopathy of prematurity(ROP)is a proliferative vascular disorder of the immature retina, and it is a major eye disease that causes blindness in children of developing and developed countries. Retinal laser photocoagulation and cryotherapy are the conventional treatment used for ROP but could cause permanent damage to retina, with a risk of complications such as visual field defect and high myopia. With more normal growth of retinal function and convenience and shorter time than coagulation therapy, intravitreal injection of anti-vascular endothelial growth factor(VEGF)agents has gradually gained popularity and has even been advocated as the treatment of choice in treating zone I, zone II posterior or aggressive ROP. However, the serious systemic complications, minimum effective dose and late recurrence caused by anti-VEGF drugs in the treatment of ROP still need to be further studied. This review focuses on the use of anti-VEGF agents for the treatment of ROP.