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.

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.

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.

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.

"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)

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.

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.

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.

The Use of Mid-Pregnancy Cervical Length to Predict Preterm Birth in Brazilian Asymptomatic Twin Gestations / O uso da medida do colo uterino no segundo trimestre de gestantes brasileiras como preditor de prematuridade na gestação gemelar

Abstract Objective To describe a reference curve for cervical length (CL) in mid-trimester twin gestations using transvaginal ultrasound (TVU) and to investigate whether short CL increases spontaneous preterm birth (sPTB) in asymptomatic twin pregnancies. Methods This was a prospective cohort study performed at 17 outpatient antenatal facilities of Brazil with women at 18 0/7 to 22 6/7 weeks of gestation who participated in a randomized clinical trial screening phase (P5 trial) between July 2015 and March 2019. TVU was performed to provide CL measurement in all screened women. Almost all women with CL ≤ 30 mm received vaginal progesterone 200mg/day and they were also randomized to receive cervical pessary or not. We considered data from the CL distribution among asymptomatic twin pregnancies and analyzed CL and its association with PTB generating receiver operating characteristics (ROC) curves and Kaplan-Meier curves. Results A total of 253 pregnant women with twins were included in the distribution curve. The mean CL was 33.7 mm and median was 35.5mm. The 10th percentile was 17.8mm. We identified a PTB rate of 73.9% (187/253) with 33.6% of sPTB < 37 (85/253) and 15% (38/253) of sPTB < 34 weeks. The best cutoff point to predict sPTB < 37 was 24.15 mm. However, the ROC curve showed a poor performance (0.64). The Kaplan-Meier survival curves identified that only CL values ≤ 20mm were associated to sPTB < 34 weeks. Conclusion A cutoff point of CL ≤ 20 mm can be interesting point to identify short cervix in Brazilian twin pregnancies. However, in Brazilian asymptomatic twin pregnancies, CL does not show a good performance to predict PTB.

Resumo Objetivo Descrever uma curva de referência da medida do colo uterino no Segundo trimestre de gestações gemelares através de ultrassonografia transvaginal (TVU) e investigar a correlação entre a medida do colo uterino (CL) e o parto prematuro espontâneo (sPTB) em pacientes assintomáticas. Métodos Foi realizado uma coorte prospectiva multicêntrica em 17 centros de referência do Brasil com mulheres com gestação gemelar entre 18 0/7 a 22 6/7 semanas de gestação que participaram da primeira fase de um ensaio clínico randomizado (P5 trial) entre Julho/2015 a Março/2019. TVU foi realizada para obter a medida do colo uterino em todas as mulheres. A maioria das mulheres com CL ≤30 mm receberam progesterona por via vaginal 200mg/dia e estas foram randomizadas para receber ou não um pessário cervical. Este estudo considerou dados da medida do colo uterino entre mulheres assintomáticas, desenvolvendo uma curva de referência para gestantes gemelares e sua capacidade de predição do parto prematuro através de curva ROC (receiver operating characteristics) e curvas de sobrevida de Kaplan-Meyer. Resultados O total de 253 gestantes foram incluídos no estudo, A média do CL foi 33.7mm e a mediana 35.5mm. O Percentil 10 do CL foi 17.8mm. A taxa de parto prematuro foi de 73.9% (187/253) com 33.6% de sPTB < 37 (85/253) e 15% (38/253) de sPTB < 34 semanas. O melhor ponto de corte para predizer sPTB < 37 foi 24.15 mm, entretanto a curva ROC demonstrou baixa performance (0.64). A curva de Kaplan-Meier para sPTB identificou que apenas CL ≤ 20 mm estavam associados a sPTB < 34 semanas. Conclusão Colo uterino ≤20 mm pode ser um interessante ponto de corte para identificar colo curto entre gestações gemelares assintomáticas brasileiras. Entretanto, a medida do colo uterino não apresentou boa performance para predizer parto prematuro.

Retinopatía de la prematuridad agresiva posterior / Aggressive Posterior Retinopathy of Prematurity

Introducción: La retinopatía del prematuro es una enfermedad ocular provocada por una alteración en la vasculogénesis de la retina, que lleva a la pérdida parcial o total de la visión. Objetivo: Presentar el primer caso, en la provincia de Santa Clara, de retinopatía de la prematuridad agresiva posterior y el tratamiento realizado. Presentación del caso: Niña prematura con más de 5 factores de riesgo al nacer que presentó retinopatía de la prematuridad agresiva posterior y se le realizó tratamiento con bevacizumab intravítreo. Conclusiones: La evolución de la niña en un período de un 1 año resultó satisfactoria con regresión total de la enfermedad. El tratamiento establecido constituye un método alternativo con buenos resultados en algunas condiciones específicas como la retinopatía del prematuro agresiva posterior(AU)

Introduction: Retinopathy of prematurity is an ocular disease caused by an alteration in retinal vasculogenesis, leading to partial or total loss of sight. Objective: To present the first case, in the province of Santa Clara, of aggressive posterior retinopathy of prematurity and the treatment performed. Case presentation: Premature girl with more than 5 risk factors at birth who presented aggressive posterior retinopathy of prematurity and was treated with intravitreal bevacizumab. Conclusions: The evolution of the girl in a period of 1 year was satisfactory with total regression of the disease. The established treatment constitutes an alternative method with good results in some specific conditions such as aggressive posterior retinopathy of prematurity(AU)

Impact of the Koala Project on clinical outcomes of preterm infants in two maternity hospitals / Impacto do Projeto Coala nos resultados clínicos de pacientes prematuros em duas maternidades

ABSTRACT Objective: To describe the impact of the Koala project (Actively Controlling Target Oxygen) on clinical outcomes in patients born with less than 36 weeks of gestation, in two maternity hospitals, comparing before and after the strategy implementation. Methods: This is an intervention study with 100 preterm infants with gestational age ≤36 weeks, who used oxygen in two maternity hospitals between January 2020 and August 2021. One of the hospitals was a private institution and the other was philanthropic. The goal for the target oxygen saturation with this project was 91-95%. Comparisons between the two stages (before and after the implementation of the project) were made evaluating the outcomes of retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, and deaths. The continuous variables were described using mean, median, standard deviation and interquartile interval. The significance level adopted was 5% and the software used was R Core Team 2021 (version 4.1.0). Results: After oxygen control use according to the Koala protocol, there was a significant reduction in the cases of retinopathy of prematurity (p<0.001) and bronchopulmonary dysplasia (p<0.001). There were no deaths in the second stage, and there was a non-significant increase in the absolute number of necrotizing enterocolitis cases. Conclusions: The Koala project seems to be an effective and feasible strategy to reduce adverse situations in the management of premature children, but research with a greater sample is needed.

RESUMO Objetivo: Descrever o impacto do projeto Coala (Controle Ativo de Oxigênio Alvo) nos desfechos clínicos em pacientes nascidos com menos de 36 semanas de gestação, em duas maternidades, comparando antes e depois da implementação da estratégia. Métodos: Trata-se de um estudo de intervenção com cem prematuros vivos, com idade gestacional ≤36 semanas, que utilizaram oxigênio em duas maternidades entre janeiro de 2020 e agosto de 2021. A meta para a saturação de oxigênio alvo com este projeto foi de 91-95%. Comparações entre as duas etapas (antes e depois da implantação do projeto) foram feitas avaliando os desfechos de retinopatia da prematuridade, displasia broncopulmonar, enterocolite necrosante e óbitos. As variáveis contínuas foram descritas por meio de média, mediana, desvio padrão e intervalo interquartil. O nível de significância adotado foi de 5% e o software empregado foi o R Core Team 2021 (versão 4.1.0). Resultados: Observou-se que, após o uso de controle de oxigênio segundo o protocolo Coala, houve redução significativa nos casos de retinopatia da prematuridade (p<0,001) e displasia broncopulmonar (p<0,001). Não houve óbitos na segunda etapa e houve aumento não significativo no número absoluto de casos de enterocolite necrosante. Conclusões: O projeto Coala parece ser uma estratégia eficaz e viável para reduzir situações adversas no manejo de crianças prematuras, mas pesquisas com amostras maiores são necessárias.

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.

Amniotic Sludge and Prematurity: Systematic Review and Meta-analysis / Sludge amniótico e prematuridade: revisão sistemática e metanálise

Abstract Objective To perform a systematic review and meta-analysis of studies on maternal, fetal, and neonatal outcomes of women with singleton pregnancies, after spontaneous conception, and with the diagnosis of amniotic sludge before 37 weeks of gestational age. Data Sources We conducted a search on the PubMed, Cochrane, Bireme, and Theses databases until June 2022. Selection of Studies Using the keywords intra-amniotic sludge or fluid sludge or echogenic particles, we found 263 articles, 132 of which were duplicates, and 70 were discarded because they did not meet the inclusion criteria. Data Collection The articles retrieved were analyzed by 2 reviewers; 61 were selected for full-text analysis, 18 were included for a qualitative analysis, and 14, for a quantitative analysis. Data Synthesis Among the maternal outcomes analyzed, there was an increased risk of preterm labor (95% confidence interval [95%CI]: 1.45-2.03), premature rupture of ovular membranes (95%CI: 1.99-3.79), and clinical (95%CI: 1.41-6.19) and histological chorioamnionitis (95%CI: 1.75-3.12). Regarding the fetal outcomes, there was a significant increase in the risk of morbidity (95%CI: 1.80-3.17), mortality (95%CI: 1.14-18.57), admission to the Neonatal Intensive Care Unit (NICU; 95%CI: 1.17-1.95), and neonatal sepsis (95%CI: 2.29-7.55). Conclusion The results of the present study indicate that the presence of amniotic sludge is a risk marker for preterm delivery. Despite the heterogeneity of the studies analyzed, even in patients with other risk factors for prematurity, such as short cervix and previous preterm delivery, the presence of amniotic sludge increases the risk of premature labor. Moreover, antibiotic therapy seems to be a treatment for amniotic sludge, and it may prolong pregnancy.

Resumo Objetivo Realizar revisão sistemática e metanálise de estudos que avaliaram os desfechos maternos, fetais e neonatais em gestantes de gravidez única, após concepção espontânea, e com o diagnóstico de sludge amniótico antes de 37 semanas de idade gestacional. Fontes dos dados Realizou-se uma pesquisa nas bases de dados PubMed, Cochrane, Bireme e Teses até junho de 2022. Seleção dos estudos Usando as palavras-chave intra-amniotic sludge ou fluid sludge ou echogenic particles, foram encontrados 263 artigos, 132 dos quais eram duplicatas, e 70 foram descartados por não corresponderem aos critérios de inclusão. Coleta de dados Os artigos encontrados foram analisados por 2 revisores; 61 foram selecionados para análise de texto completo, 18 foram incluídos em uma análise qualitativa e 14, em uma análise quantitativa. Síntese dos dados Entre os desfechos maternos analisados, houve aumento do risco de trabalho de parto prematuro (intervalo de confiança de 95% [IC95%]: 1.45-2.03), rotura prematura de membranas ovulares (IC95%: 1.99-3.79), e corioamnionite clínica (IC95%: 1.41-6.19) e histológica (IC95%: 1.75-3.12). Em relação aos desfechos fetais, houve aumento significativo do risco de morbidade (IC95%: 1.80-3.17), mortalidade (IC95%: 1.14-18.57), admissão em Unidade de Tratamento Intensivo (UTI) neonatal (IC95%: 1.17-1.95) e sepse neonatal (IC95%: 2.29-7.55). Conclusão Os resultados do presente estudo indicam que a presença de sludge amniótico é um marcador de risco para parto prematuro. Apesar da heterogeneidade dos estudos analisados, até mesmo em pacientes com outros fatores de risco para prematuridade, como colo curto e trabalho de parto prematuro anterior, a presença de sludge amniótico aumenta o risco de trabalho de parto prematuro na gestação. Além do mais, a antibioticoterapia parece ser um tratamento para o sludge amniótico, e pode ser capaz de prolongar a gravidez.

Temperature curve of raw human milk heated by different methods: experimental study / Curva de temperatura de la leche humana cruda sometida a calentamiento por diferentes métodos: estudio experimental / Curva de temperatura do leite humano cru submetido à aquecimento por diferentes métodos: estudo experimental

ABSTRACT Objective: To analyze the temperature curve of raw or pasteurized human milk exposed to different heating methods. Method: Experiments with volumes of 5 ml to 100 ml of human milk were carried out between 2016 and 2021 and analyzed according to the exposure time by different heating methods. Descriptive statistics included the calculation of means, medians, minimum and maximum values, measures of dispersion and standard deviation. Results: The thermal curve made it possible to identify the heating of human milk close to body temperature when subjected to a water bath and microwaves. Milk exposed to room temperature (21°C) was unable to reach this temperature. When heated in a water bath at 40°C, smaller volumes reached body temperature between 3 and 5 minutes, while in a microwave at 50% power, practically all volumes reached temperature. Conclusion: The temperature curves of raw or pasteurized human milk were constructed, and it was possible to verify its behavior using different heating methods for administering the food in a neonatal intensive care unit, considering the volume, type and time of heating and temperature.

RESUMEN Objetivo: Analizar la curva de temperatura de la leche humana cruda o pasteurizada expuesta a diferentes métodos de calentamiento. Método: Se realizaron experimentos con volúmenes de 5 ml a 100 ml de leche humana entre 2016 y 2021 y se analizaron en función del tiempo de exposición mediante diferentes métodos de calentamiento. La estadística descriptiva incluyó el cálculo de medias, medianas, valores mínimos y máximos, medidas de dispersión y desviación estándar. Resultados: La curva térmica permitió identificar el calentamiento de la leche humana próximo a la temperatura corporal cuando se sometió a baño maría y microondas. La leche expuesta a temperatura ambiente (21°C) fue incapaz de alcanzar esta temperatura. Cuando se calentó en un baño de agua a 40°C, los volúmenes más pequeños alcanzaron la temperatura corporal entre 3 y 5 minutos, mientras que en un microondas al 50% de potencia, prácticamente todos los volúmenes alcanzaron la temperatura. Conclusión: Se construyeron las curvas de temperatura de la leche humana cruda o pasteurizada y se pudo comprobar su comportamiento utilizando diferentes métodos de calentamiento para administrar el alimento en una unidad de cuidados intensivos neonatales, teniendo en cuenta el volumen, el tipo y el tiempo de calentamiento y la temperatura.

RESUMO Objetivo: Analisar a curva de temperatura do leite humano cru ou pasteurizado exposto a diferentes métodos de aquecimento. Método: Experimentos com volumes de 5 ml a 100 ml de leite humano foram realizados entre 2016 e 2021 e analisados segundo o tempo de exposição por diferentes métodos de aquecimento. A estatística descritiva incluiu o cálculo das médias, medianas, valores mínimos e máximos, medidas de dispersão e desvio padrão. Resultados: A curva térmica permitiu identificar o aquecimento do leite humano próximo da temperatura corporal quando submetidos a banho-maria e micro-ondas. O leite exposto à temperatura ambiente (21°C) não foi capaz de atingir tal temperatura. No aquecimento em banho-maria a 40°C, volumes menores alcançaram a temperatura corporal entre 3 e 5 minutos, enquanto em micro-ondas na potência de 50%, praticamente todos os volumes alcançaram essa temperatura. Conclusão: As curvas de temperatura do leite humano cru ou pasteurizado foram construídas, sendo possível verificar o seu comportamento mediante diferentes métodos de aquecimento para administração do alimento em unidade de terapia intensiva neonatal, considerando o volume, tipo e tempo de aquecimento e temperatura.