Premature newborns with extremely low birth weight are the main category of infants having to undergo one or more red-cell transfusions during the neonatal period in order to treat anemia. Presently, there are two major transfusion strategies: the liberal strategy aimed at maintaining higher hemoglobin levels, and the restrictive one when blood is transfused at lower hemoglobin levels. In our study, we aimed to compare outcomes and the incidence of anemia after discharge during the first 24 months of corrected age in infants with extremely low birth weight who had received red-cell transfusions according to the restrictive or liberal strategy. The study was approved by the Biomedical Research Ethics Committee (minutes No.12 of 17 November 2016) and the Scientific Council (minutes No.19 of 29 November 2016) of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of Russia. This was a single-center retrospective cohort study carried out at clinical departments of the Institute of Neonatology and Pediatrics of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of Russia. The included infants were divided into 2 groups: group 1 – infants who had received RBC transfusions following the liberal strategy; group 2 – infants in whom the restrictive transfusion strategy had been used. We looked at the incidence of such outcomes as retinopathy of prematurity (ROP) ≥ stage III, necrotizing enterocolitis (NEC) ≥ stage II, bronchopulmonary dysplasia (BPD), intraventricular hemorrhages (IVH) ≥ grade II, periventricular leukomalacia (PVL), anemia after discharge at a corrected age (CA) of 1, 3, 6, 12, 18 and 24 months. The gestational age of the newborns ranged from 24 to 28 weeks. The frequency of red-cell transfusions was 136/164 (82.9%) in group 1 versus 149/216 (68.9%) in group 2, with the median volume of transfusions of 29.3 mL/kg (IQR 17.5–51.8 mL/kg) in group 1 and 19.5 mL/kg (IQR 15.0–29.5 mL/kg) in group 2, p 0.05. There were no significant differences in the incidence of BPD, IVH ≥ grade II, PVL, ROP ≥ stage III between the study groups. The incidence of NEC ≥ stage II was 1.6 times higher in group 2 than in group 1. The incidence of anemia after discharge was lower in group 1 compared to group 2 at a CA of 1 and 3 months (32/72 (44.4%) vs. 106/166 (63.8%), p = 0.026 at 1 month, 28/72 (38.9%) vs. 90/166 (54.2%), p = 0.042 at 3 months). There were no reports of severe anemia after discharge in either of the groups. After 6 months CA there was no difference in the incidence of anemia between the groups. The use of the restrictive red-cell transfusion strategy did not lead to a clinically significant increase in the incidence of ROP ≥ stage III, BPD, PVL, IVH ≥ grade II or anemia after 6 months of CA. However, the risk of NEC ≥ stage II in the restrictive strategy group was 1.6 times higher than in the liberal one, which requires further analysis.

BACKGROUND: Bowel ultrasound (US) is one of the methods used to enhance diagnostic accuracy of necrotizing enterocolitis (NEC) and its associated complications in premature newborns. AIM: To explore the diagnostic accuracy of bowel US in extremely low birth weight (ELBW) infants with NEC. METHODS: A single-center retrospective case-control study included 84 extremely low birth weight (ELBW) infants. The infants were divided into three groups: Group 1 - infants with NEC (n = 26); Group 2 - infants with feeding problems (n = 28); Group 3 - control group (n = 30). RESULTS: The specific bowelUSfindings in premature newborns withNEC(stage 3) included bowelwall thinning, complex (echogenic) ascites, and pneumoperitoneum, p < 0.05. The diagnostic effectiveness of these sonographic signs was 96.8% (sensitivity 75.0% and specificity 97.6%), p < 0.05. These findings with high specificity were associated with the need for surgical intervention, poor outcomes, or increased mortality. Stage 2 NEC which did not require surgery showed impaired differentiation of the bowel wall layers, absent or decreased bowel peristalsis, pneumatosis intestinalis, portal venous gas, or simple ascites, with a diagnostic accuracy of 82.9% (sensitivity 55.6%, specificity 91.4%, p < 0.05). CONCLUSIONS: Bowel US can be used as an adjunct to abdominal radiography to aid in the diagnosis of infants with suspected NEC by providing more detailed evaluation of the intestine.

In recent years, some new evidence on the role of Malassezia in late-onset sepsis in immunocompromised patients have been published, but there are still very few studies with special focus on newborns. The prevalence of Malassezia-associated conditions in 3519 newborn patients of general and surgical neonatal intensive care units (NICU) was assessed. All patients underwent pharyngeal and rectal swab screening for Malassezia spp. Identification of Malassezia spp. was carried out with the use of an adapted nutrient media, microscopic assessment of yeast cell morphology, and real-time PCR analysis. Malassezia furfur-induced invasive mycoses (IM) were developed 2.5 times more often in very low birth weight (VLBW) M. furfur-positive newborns, than in neonates with birth weight ≥1500 g, and affecting 15.8 % of VLBW infants. Funguria occurred 16 times more often in VLBW babies, but fungemia incidence was similar for both weight categories. Gastrointestinal (GI) colonization was found in 94.6 % of Malassezia-positive population, and in 8 % of all studied neonates. Among IM patients, death rate was 6.5 %. The specific pathogen was highly detectable by a combination of real-time PCR and an adapted nutrient media. Colonization with M. furfur in newborns was associated with low gestational age, VLBW, and long stay in NICU. The findings emphasize the need to monitor colonization and infection with M. furfur in neonates, staying in ICU for more than two weeks and to improve current diagnostic approaches by using real-time PCR and an adapted nutrient media for M. furfur isolation.

BACKGROUND:Umbilical cord blood is used for the testing of various parameters in newborns. However, data on its applicability for hemostasis assays is insufficient. OBJECTIVE:To evaluate whether umbilical cord blood can be used for standard tests, thromboelastometry and thrombodynamics for preterm and term newborns. METHODS:187 newborns were included in the study. Blood was taken from the umbilical cord and by venipuncture of the newborn. Clotting times, fibrinogen, D-dimer, thromboelastometry and thrombodynamics were measured. RESULTS:Clotting times and fibrinogen indicated a hypocoagulable shift, while thromboelastometry and thrombodynamics showed a hypercoagulable shift in hemostasis in umbilical cord blood compared to newborn blood. D-dimer indicated an enhanced process of thrombus lysis in newborn blood compared to cord blood. Collecting blood into a tube with the addition of a contact pathway inhibitor did not significantly change the global assay parameters in either umbilical cord blood or newborn blood. In the thrombodynamics assay, spontaneous clotting was detected but suppressed by the addition of a tissue factor inhibitor. CONCLUSIONS:Hemostasis in cord and newborn blood differs for both global and standard tests. Hypercoagulability in newborns registered with the global assay thrombodynamics is associated with the presence of tissue factor in the blood. IMPACT STATEMENT:1. We found a hypercoagulation shift in newborns compared with the adult references, possibly due to the presence of tissue factor in blood. 2. Blood coagulation is enhanced in cord blood compared with blood sampled from the vein of a newborn according to thromboelastometry and thrombodynamics assays. 3. Clotting times and fibrinogen concentrations in cord blood differ from these parameters in newborn blood. 4. Studying of the (patho)physiological features of hemostasis in newborns should consider differences in cord blood and vein sampled blood.

In this study, we sought to determine fecal cytokine levels in very preterm newborns at the onset of non-specific clinical symptoms of necrotizing enterocolitis (NEC) and decreased gastrointestinal (GI) motility. The study was approved by the Ethics Committee and the Scientific Council of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after the Academician V. I. Kulakov of Ministry of Healthcare of the Russian Federation. Each patient’s parents gave their informed consent to their child’s participation in the study. The study was conducted at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after the Academician V. I. Kulakov over the period from June 2020 to December 2022. Fecal samples from preterm neonates with gestational age ≤ 32 weeks treated at the A.G. Antonov ICU were collected daily over their first 14 days of life. Samples from 46 newborns were selected for analysis: fecal samples collected on the day of an enteral feeding intolerance episode and fecal samples from controls who had not developed non-specific clinical symptoms of NEC or decreased GI motility, collected on the day when enteral intake reached 100 ml/kg/day. Based on the results of NEC and decreased GI motility diagnosis, stool samples were retrospectively divided into 3 groups: an NEC group (n = 8), a decreased GI motility group (n = 14) and a control group (n = 24). In the fecal samples of the very preterm newborns with NEC stage ≥ II, there was a significant increase in IL-6, IL-8, IL-10, TNF-a levels at the onset of initial symptoms of the disease. At the same time, the cytokine profile of the feces of the decreased GI motility patients did not differ significantly from the control group in any of the parameters. In cases of NEC, high IL-6, IL-8, IL-10 and TNF-a levels were detected in the patients’ stool at the onset of enteral feeding intolerance, suggesting that the method under investigation (aimed at determining the pro- and anti-inflammatory profile of fecal cytokines) may be a promising new tool for differentiating NEC from decreased GI motility in very preterm newborns.

Despite the increasing number of placenta accreta spectrum (PAS) cases in recent years, its impact on neonatal outcomes and respiratory morbidity, as well as the underlying pathogenetic mechanism, has not yet been extensively studied. Moreover, no study has yet demonstrated the effectiveness of antenatal corticosteroid therapy (CT) for the prevention of respiratory distress syndrome (RDS) in newborns of mothers with PAS at the molecular level. In this regard, microRNA (miRNA) profiling by small RNA deep sequencing and quantitative real-time PCR was performed on 160 blood plasma samples from preterm infants (gestational age: 33-36 weeks) and their mothers who had been diagnosed with or without PAS depending on the timing of the antenatal RDS prophylaxis. A significant increase in hsa-miR-199a-3p and hsa-miR-382-5p levels was observed in the blood plasma of the newborns from mothers with PAS compared to the control group. A clear trend toward the normalization of hsa-miR-199a-3p and hsa-miR-382-5p levels in the neonatal blood plasma of the PAS groups was observed when CT was administered within 14 days before delivery, but not beyond 14 days. Direct correlations were found among the hsa-miR-382-5p level in neonatal blood plasma and the hsa-miR-199a-3p level in the same sample (r = 0.49; p < 0.001), the oxygen requirements in the NICU (r = 0.41; p = 0.001), the duration of the NICU stay (r = 0.31; p = 0.019), and the severity of the newborn's condition based on the NEOMOD scale (r = 0.36; p = 0.005). Logistic regression models based on the maternal plasma levels of hsa-miR-199a-3p and hsa-miR-382-5p predicted the need for cardiotonic therapy, invasive mechanical ventilation, or high-frequency oscillatory ventilation in newborns during the early neonatal period, with a sensitivity of 95-100%. According to the literary data, these miRNAs regulate fetal organogenesis via IGF-1, the formation of proper lung tissue architecture, surfactant synthesis in alveolar cells, and vascular tone.

Platelet involvement in inflammatory and immune responses and its functional activity in various pathological conditions are actively studied. Despite there are scientific publications characterizing platelets of newborns vs. adults the data on the features of the expression of activation markers on platelets of premature infants with a complicated course of the early neonatal period are not enough. The purpose of the research was to analyze the expression of glycoproteins and activation molecules on the surface of peripheral blood platelets in newborns with congenital infection depending on gestational age (GA). Materials and methods of research: a prospective single-center case-control study was conducted in the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after V.I. Kulakov (Moscow, Russia) in March 2018 - September 2019. The expression of activation markers on resting and activated platelets on the 1st and 3rd days of life (DOL) in 158 newborns aged 24 to 38 weeks was analyzed using the flow cytometry. The patients were divided into 3 groups: group 1 (n=20) of newborns with GA 24 to 28 weeks; group 2 (n=52) of newborns with GA of 29 to 33 weeks; and group 3 (n=86) of newborns with GA of 34 weeks and older. Results: in severely preterm (G1) compared with infants of older GA on the 3rd DOL platelets had higher MPV: 11.3 (10.4-12.3) vs. 10.1 (9.6-10.3), p=0.011, and PDW: 13.1 (12.2-15.6) vs. 11.3 (10.6-12.3), p<0.001. In infectious diseases in children with GA of 29 to 33 weeks there is a lower expression of phosphatidylserine on activated platelets in the 1st DOL: 8.8 (7.5-11.1) vs. 11.2 (10.3-12.1), p=0.046, and lower the content of activated platelets expressing P-selectin on the 3rd DOL: 89.5 (87.1-92.7) vs. 93.1 (90.4-94.4), p=0.048. In newborns with GA of 34 weeks and older with congenital infection in the 1st DOL there was a higher expression of von Willebrand Factor receptor revealed: 13.9 (12.3-16.4) vs. 12.4 (10.9-14.1), p=0.028, and a higher content of dense granules in activated platelets: 0.73 (0.65-0.79) vs. 0.67 (0.60-0.71), p=0.008. By the 3rd DOL there was an increase in MPV and PDW in all groups of children (p<0.05) recorded. Conclusion: in premature infants with congenital infection the expression of structural and activation molecules on platelets undergoes greater changes during the first three days of life than in children of similar GA without infectious pathology.

Журнал для непрерывного медицинского образования врачей ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ Диагностическая точность пресепсина, прокальцитонина и С-реактивного белка у новорожденных с ранним неонатальным сепсисом: одноцентровое проспективное исследованиеРанний неонатальный сепсис (РНС) остается ведущей причиной заболеваемости и смертности новорожденных и не имеет тенденции к снижению в последние 30 лет.Необходимость максимально точно определить генерализацию инфекционного процесса привела к исследованию диагностической значимости биомаркеров системного воспалительного ответа, их кинетику и референсные значения, характерные для новорожденных.Наряду с традиционно используемыми биомаркерами, такими как С-реактивный белок (СРБ) и прокальцитонин (ПКТ), в последнее десятилетие активно изучаются маркеры, отражающие участие первой линии защиты против патогенов, экспрессирующиеся на гранулоцитах и макрофагах, среди них наиболее известен пресепсин (ПСП).ПСП представляет собой растворимую форму гликопротеина CD14 (sCD14-ST

Журнал для непрерывного медицинского образования врачей ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ Факторы, ассоциированные с развитием некротизирующего энтероколита у новорожденных с экстремально низкой массой тела при рождении: ретроспективный анализ Некротизирующий энтероколит (НЭК) -одно из перинатальных заболеваний, ассоциированных с высокой смертностью у недоношенных детей.Цель -определить факторы р иска развития НЭК у недоношенных новорожденных с экстремально низкой массой тела (ЭНМТ).Материал и методы.Проведено ретроспективное исследование «случай-контроль», в которое были включены недоношенные дети с ЭНМТ, родившиеся в ФГБУ «НМИЦ АГП им.В.И.Кулакова» Минздрава России с 2017 по 2019 г. (n=71).Дети были разделены на 2 группы: 1-я -дети, у которых развился НЭК (n=26), 2-я -группа сравнения, без развития НЭК (n=45).Были оценены данные анамнеза, клинические характеристики, результаты обследований детей в обеих группах

Журнал для непрерывного медицинского образования врачей КЛИНИЧЕСКИЕ РЕКОМЕНДАЦИИ Врожденная цитомегаловирусная инфекция (клинические рекомендации) 1 Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И.Кулакова» Министерства здравоохранения Российской Федерации, 117997, г.Москва, Российская Федерация 2 Федеральное государственное бюджетное образовательное учреждение высшего образования «Северо-Западный государственный медицинский университет имени И.И.Мечникова» Министерства здравоохранения Российской Федерации, 191015, г.Санкт-Петербург, Российская Федерация 3 Федеральное государственное бюджетное учреждение «Детский научно-клинический центр инфекционных болезней Федерального медико-биологического агентства»

Проградиентное форсированное наращивание объема энтерального питания у глубоконедоношенных детей: результаты мультицентрового проспективного рандомизированного исследованияВыбор тактики энтерального питания (ЭП) имеет решающее значение для профилактики некротизирующего энтероколита (НЭК), оптимального роста и нервно-психического развития глубоконедоношенных детей.Цель исследования -оценить безопасность и эффективность метода проградиентного наращивания (ПН) ЭП 30 мл/кг в сутки у недоношенных новорожденных гестационного возраста (ГВ) ≤32 нед по сравнению с традиционным методом вскармливания.Материал и методы.Мультицентровое проспективное рандомизированное исследование проведено на базе отделения реанимации и интенсивной терапии новорожденных (ОРИТН) им.проф.А.Г.Антонова ФГБУ «НМИЦ АГП им.В.И.Кулакова» Минздрава России и ОРИТН ГБУЗ «Московский областной перинатальный центр» с июня 2020 г. по декабрь 2021 г.В исследование вошли 287 пациентов ГВ 24/3-32/0 нед с массой тела при рождении от 475 до 2285 г.Недоношенные дети ГВ 28/0-32/0 нед были разделены на 2 группы: проградиентного (n=119) и стандартного наращивания (n=119), суточный объем увеличения энтеральной нагрузки в обеих группах составил 30 мл/кг в сутки.Новорожденные ГВ <28 нед были распределены в 3 группы: 1-я (n=15) -с ПН энтеральной нагрузки с ежедневным увеличением 30 мл/кг, 2-я (n=16) -с ПН суточного объема ЭП 20 мл/кг, 3-я (n=18) -традиционным наращиванием 20 мл/кг в сутки двукратно на 10 мл/кг.ПН представляет собой методику увеличения объема ЭП в каждое кормления на равную величину в течение суток.Результаты.Проградиентный метод наращивания ЭП способствует более быстрому достижению объема ЭП 100 и 160 мл/кг в сутки, сокращению потребности в постановке глубоких венозных линий на 20% у новорожденных массой тела <1500 г, не влияет на частоту НЭК.Суточное увеличение объема ЭП 30 мл/кг у новорожденных ГВ <28 нед безопасно и приводит к более быстрому достижению полного объема ЭП без увеличения частоты возникновения НЭК, но не влияет на продолжительность функционирования центрального и периферического венозных катетеров, продолжительность пребывания в стационаре и массо-ростовые показатели физического развития.неонатология: новости, мнения, обучение.том 11, № 2, 2023 Заключение.По результатам исследования проградиентное увеличение объема ЭП на 30 мл/кг в сутки может быть рекомендовано для глубоконедоношенных детей как безопасная и эффективная методика, позволяющая сократить сроки достижения полного ЭП без увеличения риска развития интолерантности к ЭП и НЭК.

The search for promising markers of brain damage in premature newborns is important for the development and optimization of individual diagnostic and therapeutic approaches to neuroprotection in neonatology. Objective: to evaluate the diagnostic significance of serum erythropoietin (sEPO) on the 1st day of life as a marker of perinatal brain damage in premature infants with very low birth weight (VLBW). The study protocol was approved by the Biomedical Research Ethics Committee (Minutes No.12 of 17 November 2016) and the Scientific Council (Minutes No.19 of 29 November 2016) of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after the Academician V.I. Kulakov of Ministry of Healthcare of the Russian Federation. Written informed consent to the patients' participation in the study was obtained from their parents. The study included 47 premature infants with VLBW born in 2018 at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of the Russian Federation. In these patients, sEPO was determined on the 1st day of life. Depending on the level of sEPO, infants were divided into 3 groups: group 1 – premature infants with VLBW with a low sEPO level on the 1st day of life (< 20 IU/L, n = 24); group 2 – premature infants with VLBW with an average sEPO level of 20–39 IU/L (reference values) (n = 14) – control group; group 3 – premature infants with VLBW with an elevated sEPO level (≥ 40 IU/L, n = 9). We determined the frequency of brain damage, including intraventricular hemorrhages (IVH) and periventricular leukomalacia. sEPO was not correlated with gestational age. In group 1, IVH ≤ Grade II was observed in 4/24 (16.7%) infants; in group 2, IVH ≤ Grade II was observed in 3/14 (21.4%) infants, and 1/14 (7.1%) infant had IVH Grade III; in group 3, IVH ≤ Grade II was noted in 1/9 (11.1%) infant, and IVH Grade III – in 1/9 (11.1%) infant, p > 0.05. There were no cases of periventricular leukomalacia. A high sEPO level on the 1st day of life in premature infants with VLBW was not associated with an increased risk of perinatal brain damage. The clinical value and practical significance of the determination of sEPO on the 1st day of life as a marker of perinatal brain damage in premature infants with VLBW did not demonstrate any benefits. Further studies are required to assess the role of sEPO in predicting neonatal outcomes.

Reticulocyte hemoglobin content (RET-He) is a promising marker of iron deficiency (ID) in newborns. Objective: to determine the diagnostic value of RET-He as a marker of ID in premature newborns with very low birth weight (VLBW). We conducted a single-center retrospective cohort study, which included 66 premature infants admitted to the National Medical Research Center for Obstetrics, Gynecology and Perinatology named the Academician V.I. Kulakov of the Ministry of Healthcare of the Russian Federation. Data were obtained from January 2016 to December 2018. The gestational age ranged from 29 to 32 weeks. Laboratory examination included blood tests on the 1 st and 3 rd day of life, then every 10–14 days until the day of life, then every 10–14 days the Institute of Neonatology and Pediatrics; discharge from hospital, and the measurements of serum iron, ferritin, transferrin on the 7 th until the discharge from hospital. This clinical study was approved by the Biomedical Research Ethics Committee (Minutes No.12 of 17 November 2016) and the Scientific Council (Minutes No.19 of 29 November 2016) of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after the Academician V.I. Kulakov of Ministry of Healthcare of the Russian Federation. RET-He was the highest at birth and declined gradually thereafter in premature newborns reaching the lowest values after 3 weeks of life (median (interquartile range) 28.4 (25.8–34.8) pg (on the 1st day of life – 40.0 (35.7–41.9) pg and 33.5 (29.2–36.6) pg at the time of discharge). A low RET-He level was associated with low reticulocytes, with no changes in hemoglobin. There was a positive correlation between RET-He and MCH. D-He decreased from 1 to 42 days of life as a marker of increasing anemia. There was a negative correlation between RET-He and Hypo-He (p < 0.005). Starting from 42 days of life, or by the time of discharge, 32% of premature infants (n = 21) had a low ferritin level and 77% (n = 51) of premature infants had a low RET-He level, of which 21 infants developed ID (a positive correlation between RET-He and ferritin after 42 days of life (r = 0.34, p = 0.046)). There was no correlation between RET-He and ferritin in newborns without ID. Also, there were no correlations between RET-He and iron and RET-He and transferrin. After 42 days of life, RET-He less than 28.4 pg was a marker of ID (sensitivity 83.3% and specificity 93.7%). Low RET-He, D-He, RBC-Hе and high microR, Hypo-He were the earliest markers of ID in premature infants which predicted a decrease in serum iron and ferritin levels. RET-He, D-Не and Hypo-He are biomarkers with accurate diagnostic value of ID in premature infants with VLBW.

КЛИНИЧЕСКИЕ РЕКОМЕНДАЦИИ Апноэ недоношенных (проект клинических рекомендаций)В статье представлен проект клинических рекомендаций по ведению новорожденных с апноэ