Analysis of the changes in the management of preterm newborns born in a Spanish third-level hospital in the past 10 years.

BACKGROUND: Preterm newborns require the use of the best and most current strategies to treat and prevent both acute pathology and associated sequelae. This study aimed to compare the differences in the management of preterm newborns over 10 years in a tertiary hospital in Spain and its impact on height, weight, and neurological development in the medium term. METHODS: We conducted a retrospective, observational, and analytical study examining the management and clinical variables in preterm newborns under 32 weeks of gestational age who were born in our hospital in 2011 and 2021. RESULTS: Twenty-six newborns were included in the study. Significant differences in magnesium sulfate use, continuous positive airway pressure immediately after birth, and non-invasive mechanical ventilation during hospitalization were observed. Differences were found in the use of parenteral nutrition and the timing of initiation of enteral feeding. We did not observe differences in the neurological or weight evolution in the medium term. CONCLUSIONS: Significant differences in managing preterm newborns in these 10 years were observed. Lower mortality and alterations in central nervous system ultrasound and, significantly, less growth retardation during admission in 2021 have been observed; however, it does not manifest with improvement in long-term somatometrics or neurological prognosis.

INTRODUCCIÓN: La inmadurez de los recién nacidos pretérmino (RNP) requiere el empleo de las mejores y más actuales estrategias para tratar la patología aguda y prevenir sus eventuales secuelas asociadas. El objetivo planteado es comparar las diferencias en el manejo de RNP a lo largo de diez años en un hospital de tercer nivel en España y su impacto en el desarrollo neurológico y póndero-estatural a medio plazo. MÉTODOS: Estudio retrospectivo, observacional y analítico examinando variables del manejo y clínicas de todos los RNP menores de 32 semanas de edad gestacional nacidos en nuestro hospital (nivel III-A) en 2011 y en 2021. RESULTADOS: Se incluyeron 26 infantes (2011: 10 niños, 2021: 16 niños). Observamos diferencias significativas en el uso prenatal de sulfato de magnesio, mayor uso de presión positiva continua en la vía aérea (CPAP) al ingreso y ventilación mecánica no invasiva durante el ingreso, retraso en el uso de surfactante, empleo de alimentación intravenosa e inicio precoz de la alimentación enteral. Existe una menor tasa de mortalidad y desnutrición postnatal en 2021. No observamos diferencias en la evolución neurológica o ponderal a medio plazo. CONCLUSIONES: Existen diferencias en el manejo de los prematuros en estos 10 años con mayor ajuste a las guías nacionales e internacionales vigentes. Esto se relaciona con menor mortalidad y alteraciones en la ecografía del sistema nervioso central y, significativamente, con un menor retraso en el crecimiento durante el ingreso en 2021; no se demostró mejoría del pronóstico somatométrico o neurológico a largo plazo.

Prevalencia de osteopenia del prematuro antes y después de la implementación de una estrategia temprana de manejo fosfocálcico / Prevalence of osteopenia of prematurity before and after implementing an early strategy with the use of calcium and phosphate

Introducción. Con el uso de la nutrición parenteral agresiva en recién nacidos de muy bajo peso, se detectaron alteraciones del metabolismo fosfocálcico. En 2016 se implementó una estrategia de prevención a través del monitoreo fosfocálcico y su suplementación temprana. El objetivo fue estudiar si esta estrategia disminuye la prevalencia de osteopenia e identificar factores de riesgo asociados. Población y métodos. Estudio cuasiexperimental que comparó la prevalencia de osteopenia entre dos grupos: uno después de implementar la estrategia de monitoreo y suplementación fosfocálcica (01/01/2017-31/12/2019), y otro previo a dicha intervención (01/01/2013-31/12/2015). Resultados. Se incluyeron 226 pacientes: 133 pertenecen al período preintervención y 93 al posintervención. La prevalencia de osteopenia global fue del 26,1 % (IC95% 20,5-32,3) y disminuyó del 29,3 % (IC95% 21,7-37,8) en el período preintervención al 21,5 % (IC95% 13,6-31,2) en el posintervención, sin significancia estadística (p = 0,19). En el análisis multivariado, el puntaje NEOCOSUR de riesgo de muerte al nacer, recibir corticoides posnatales y el período de intervención se asociaron de manera independiente a osteopenia. Haber nacido luego de la intervención disminuyó un 71 % la probabilidad de presentar fosfatasa alcalina >500 UI/L independientemente de las restantes variables incluidas en el modelo. Conclusión. La monitorización y suplementación fosfocálcica precoz constituye un factor protector para el desarrollo de osteopenia en recién nacidos con muy bajo peso al nacer.

Introduction. With the use of aggressive parenteral nutrition in very low birth weight infants, alterations in calcium and phosphate metabolism were detected. In 2016, a prevention strategy was implemented through calcium phosphate monitoring and early supplementation. Our objective was to study whether this strategy reduces the prevalence of osteopenia and to identify associated risk factors. Population and methods. Quasi-experiment comparing the prevalence of osteopenia between two groups: one after implementing the calcium phosphate monitoring and supplementation strategy (01/01/2017­12/31/2019) and another prior to such intervention (01/01/2013­12/31/2015). Results. A total of 226 patients were included: 133 in the pre-intervention period and 93 in the post-intervention period. The overall prevalence of osteopenia was 26.1% (95% CI: 20.5­32.3) and it was reduced from 29.3% (95% CI: 21.7­37.8) in the pre-intervention period to 21.5% (95% CI: 13.6­31.2) in the post-intervention period, with no statistical significance (p = 0.19). In the multivariate analysis, the NEOCOSUR score for risk of death at birth, use of postnatal corticosteroids, and the intervention period were independently associated with osteopenia. Being born after the intervention reduced the probability of alkaline phosphatase > 500 IU/L by 71%, regardless of the other variables included in the model. Conclusion. Calcium phosphate monitoring and early supplementation is a protective factor against the development of osteopenia in very low birth weight infants.

Monitoring SpO2: The Basics of Retinopathy of Prematurity (Back to Basics) and Targeting Oxygen Saturation.

Oxygen (O2) is a drug frequently used in newborn care. Adverse effects of hypoxia are well known but the damaging effects of excess oxygen administration and oxidative stress have only been studied in the last 2 decades. Many negative effects have been described, including retinopathy of prematurity . Noninvasive pulse oximetry (SpO2) is useful to detect hypoxemia but requires careful evaluation and understanding of the frequently changing relationship between O2 and hemoglobin to prevent hyperoxemia. Intention to treat SpO2 ranges should be individualized for every newborn receiving supplemental O2, according to gestational age, post-natal age, and clinical condition.

Glycogen Synthase Kinase-3ß Inhibitor VP3.15 Ameliorates Neurogenesis, Neuronal Loss and Cognitive Impairment in a Model of Germinal Matrix-intraventricular Hemorrhage of the Preterm Newborn.

Advances in neonatology have significantly reduced mortality rates due to prematurity. However, complications of prematurity have barely changed in recent decades. Germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most severe complications of prematurity, and these children are prone to suffer short- and long-term sequelae, including cerebral palsy, cognitive and motor impairments, or neuropsychiatric disorders. Nevertheless, GM-IVH has no successful treatment. VP3.15 is a small, heterocyclic molecule of the 5-imino-1,2,4-thiadiazole family with a dual action as a phosphodiesterase 7 and glycogen synthase kinase-3ß (GSK-3ß) inhibitor. VP3.15 reduces neuroinflammation and neuronal loss in other neurodegenerative disorders and might ameliorate complications associated with GM-IVH. We administered VP3.15 to a mouse model of GM-IVH. VP3.15 reduces the presence of hemorrhages and microglia in the short (P14) and long (P110) term. It ameliorates brain atrophy and ventricle enlargement while limiting tau hyperphosphorylation and neuronal and myelin basic protein loss. VP3.15 also improves proliferation and neurogenesis as well as cognition after the insult. Interestingly, plasma gelsolin levels, a feasible biomarker of brain damage, improved after VP3.15 treatment. Altogether, our data support the beneficial effects of VP3.15 in GM-IVH by ameliorating brain neuroinflammatory, vascular and white matter damage, ultimately improving cognitive impairment associated with GM-IVH.

Prevalence of osteopenia of prematurity before and after implementing an early strategy with the use of calcium and phosphate. / Prevalencia de osteopenia del prematuro antes y después de la implementación de una estrategia temprana de manejo fosfocálcico.

Introduction. With the use of aggressive parenteral nutrition in very low birth weight infants, alterations in calcium and phosphate metabolism were detected. In 2016, a prevention strategy was implemented through calcium phosphate monitoring and early supplementation. Our objective was to study whether this strategy reduces the prevalence of osteopenia and to identify associated risk factors. Population and methods. Quasi-experiment comparing the prevalence of osteopenia between two groups: one after implementing the calcium phosphate monitoring and supplementation strategy (01/01/2017-12/31/2019) and another prior to such intervention (01/01/2013-12/31/2015). Results. A total of 226 patients were included: 133 in the pre-intervention period and 93 in the post-intervention period. The overall prevalence of osteopenia was 26.1% (95% CI: 20.5-32.3) and it was reduced from 29.3% (95% CI: 21.7-37.8) in the pre-intervention period to 21.5% (95% CI: 13.6-31.2) in the post-intervention period, with no statistical significance (p = 0.19). In the multivariate analysis, the NEOCOSUR score for risk of death at birth, use of postnatal corticosteroids, and the intervention period were independently associated with osteopenia. Being born after the intervention reduced the probability of alkaline phosphatase > 500 IU/L by 71%, regardless of the other variables included in the model. Conclusion. Calcium phosphate monitoring and early supplementation is a protective factor against the development of osteopenia in very low birth weight infants.

Introducción. Con el uso de la nutrición parenteral agresiva en recién nacidos de muy bajo peso, se detectaron alteraciones del metabolismo fosfocálcico. En 2016 se implementó una estrategia de prevención a través del monitoreo fosfocálcico y su suplementación temprana. El objetivo fue estudiar si esta estrategia disminuye la prevalencia de osteopenia e identificar factores de riesgo asociados. Población y métodos. Estudio cuasiexperimental que comparó la prevalencia de osteopenia entre dos grupos: uno después de implementar la estrategia de monitoreo y suplementación fosfocálcica (01/01/2017-31/12/2019), y otro previo a dicha intervención (01/01/2013-31/12/2015). Resultados. Se incluyeron 226 pacientes: 133 pertenecen al período preintervención y 93 al posintervención. La prevalencia de osteopenia global fue del 26,1 % (IC95% 20,5-32,3) y disminuyó del 29,3 % (IC95% 21,7-37,8) en el período preintervención al 21,5 % (IC95% 13,6-31,2) en el posintervención, sin significancia estadística (p = 0,19). En el análisis multivariado, el puntaje NEOCOSUR de riesgo de muerte al nacer, recibir corticoides posnatales y el período de intervención se asociaron de manera independiente a osteopenia. Haber nacido luego de la intervención disminuyó un 71 % la probabilidad de presentar fosfatasa alcalina >500 UI/L independientemente de las restantes variables incluidas en el modelo. Conclusión. La monitorización y suplementación fosfocálcica precoz constituye un factor protector para el desarrollo de osteopenia en recién nacidos con muy bajo peso al nacer.

Sex differences in preterm respiratory morbidity: A recent whole-population study.

AIM: To determine whether there were differences between male and female infants in respiratory morbidity in a whole population of extremely preterm infants, including infants born below 24 weeks of gestation. METHODS: Retrospective whole-population study of all infants <28 weeks of gestation admitted to a neonatal unit in England from 2014 to 2019. Bronchopulmonary dysplasia (BPD) development was defined as any respiratory support at 36 weeks postmenstrual age. RESULTS: The 11 844 infants had a median (IQR) gestational age of 26.0 (24.9-27.1) weeks and a birth weight of 0.81 (0.67-0.96) kg. The duration of invasive ventilation was longer in male compared to female infants who were born at 24-27 completed weeks of gestation (p < 0.001), but not significantly different between male and female infants born at 22 and 23 weeks of gestation (p = 0.446). The incidence of BPD was higher in male compared to female infants born at 24-27 weeks of gestation (p < 0.001) but not different between male and female infants born at 22 and 23 weeks of gestation (p = 0.148). CONCLUSION: Respiratory morbidity was more pronounced in male compared to female extremely preterms, only in gestations 24-27 completed weeks. Male predominance was absent in infants born below 24 weeks of gestation.

Newborn Screening for Severe Combined Immunodeficiency: Lessons Learned from Screening and Follow-Up of the Preterm Newborn Population.

Newborn screening (NBS) for Severe Combined Immunodeficiency (SCID) by measurement of T-cell receptor excision circles (TRECs) successfully identifies newborns with SCID and severe T-cell lymphopenia, as intended. At the same time, NBS programs face the challenge of false positive results, with a disproportionately high number in the premature newborn population. This study evaluates TREC values and SCID screening outcomes in premature newborns and elucidates evidence-based SCID screening practices that reduce unnecessary follow-up activities in this population. De-identified individual SCID newborn screening data and aggregate SCID screening data were obtained from seven states across the US for babies born between 2018 and 2020. Relevant statistics were performed on data pooled from these states to quantify screening performance metrics and clinical impact on various birth and gestational age categories of newborns. The data were normalized using multiples-of-the-median (MoM) values to allow for the aggregation of data across states. The aggregation of NBS data across a range of NBS programs highlighted the trajectory of TREC values over time, both between and within newborns, and provides evidence for improved SCID screening recommendations in the premature and low birth weight population.

Bone Status and Early Nutrition in Preterm Newborns with and without Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR) together with preterm birth could be harmful to bone health. The aim of the study was to examine bone status in IUGR versus non-IUGR preterms and to analyze the nutritional management best correlated with its improvement. Newborns < 34 weeks of gestational age (wGA), 75 IUGR and 75 non-IUGR, admitted to the Neonatal Intensive Care Unit of the University Hospital of Padova were enrolled and monitored from birth until 36 wGA through anthropometry (weight, length, head circumference, lower limb length (LLL)), biochemistry, bone quantitative ultrasound assessment of bone status (metacarpus bone transmission time, mc-BTT, us) and nutritional intakes monitoring during parenteral nutrition. IUGR compared to non-IUGR showed lower mean mc-BTT (0.45 vs. 0.51, p = 0.0005) and plasmatic phosphate (1.45 vs. 1.79, p < 0.001) at birth. Mc-BTT at 36 wGA, though equal between groups, correlated in IUGR newborns with basal phosphate, mean total energy of the first week and month (positively) and days to reach full enteral feeding (negatively). Lower i.v. vitamin D intake, LLL and prolonged total parenteral nutrition predicted worse mc-BTT at 36 wGA in the enrolled infants. These results suggest that preterms and in particular IUGR newborns need special nutritional care to promote bone development.

Oropharyngeal administration of colostrum targeting gut microbiota and metabolites in very preterm infants: protocol for a multicenter randomized controlled trial.

BACKGROUND: Oropharyngeal administration of colostrum (OAC) has an immune-stimulating effect on oropharyngeal-associated lymphoid tissue, and can promote the maturation of the gastrointestinal tract. However, how OAC promotes intestinal maturation in preterm infants by altering gut microbiota remains unclear. We aim to assess changes in gut microbiota and metabolites after OAC in very preterm infants. METHODS: A multicenter, double-blind, randomized controlled trial will be conducted in three large neonatal intensive care units in Shenzhen, China, with preterm infants with gestational age less than 32 weeks at birth and birth weight less than 1500 g. It is estimated that 320 preterm infants will be enrolled in this study within one year. The intervention group will receive oropharyngeal administration of 0.2 ml colostrum every 3 h, starting between the first 48 to 72 h and continued for 5 consecutive days. Following a similar administration scheme, the control group will receive oropharyngeal administration of sterile water. Stool samples will be collected at the first defecation, as well as on the 7th, 14th, 21st and 28th days after birth for analysis of effect of OAC on gut microbiota and metabolites through 16sRNA gene sequencing and liquid chromatography-mass spectrometry. DISCUSSION: This proposal advocates for the promotion of OAC as a safe and relatively beneficial protocol in neonatal intensive care units, which may contribute to the establishment of a dominant intestinal flora. Findings of this study may help improve the health outcomes of preterm infants by establishment of targeted gut microbiota in future studies. TRIAL REGISTRATION: NCT05481866 (registered July 30, 2022 on ClinicalTrials.gov).

Anti-Inflammatory and Anti-Allergic Properties of Colostrum from Mothers of Full-Term and Preterm Babies: The Importance of Maternal Lactation in the First Days.

Our narrative review focuses on colostrum components, particularly those that influence the neonatal immune system of newborns. Colostrum is secreted in small volumes by the alveolar cells of the breast during the first two to five days after birth. Colostrum is poor in fat and carbohydrates, with larger protein and bioactive compounds than mature milk. It plays a crucial role in driving neonates' immunity, transferring those immunological factors which help the correct development of the neonatal immune system and support establishing a healthy gut microbiome. The newborn has an innate and adaptive immune system deficiency, with a consequent increase in infection susceptibility. In particular, neonates born prematurely have reduced immunological competencies due to an earlier break in the maternal trans-placenta transfer of bioactive components, such as maternal IgG antibodies. Moreover, during pregnancy, starting from the second trimester, maternal immune cells are conveyed to the fetus and persist in small quantities post-natal, whereby this transfer is known as microchimerism (MMc). Thus, preterm newborns are deficient in this maternal heritage, and have their own immune system under-developed, but colostrum can compensate for the lack. Early breastfeeding, which should be strongly encouraged in mothers of preterm and full-term babies, provides those immunomodulant compounds that can act as a support, allowing the newborn to face immune needs, including fronting infections and establishing tolerance. Moreover, making mothers aware that administering colostrum helps their infants in building a healthy immune system is beneficial to sustain them in the difficult post-partum period.

Proteomics-based Mapping of Bronchopulmonary Dysplasia-associated Changes in Non-invasively Accessible Oral Secretions.

OBJECTIVE: To determine if oral secretions (OS) can be used as a non-invasively collected body fluid, in lieu of tracheal aspirates (TA), to track respiratory status and predict bronchopulmonary dysplasia (BPD) development in infants born <32 weeks. STUDY DESIGN: This was a retrospective, single-center cohort study that included data and convenience samples from week-of-life (WoL) 3 from two independent preterm infant cohorts. Using previously banked samples, we applied our sample-sparing, high-throughput proteomics technology to compare OS and TA proteomes in infants born <32 weeks admitted to the Neonatology Intensive Care Unit (NICU) (Cohort 1; N=23 infants). In a separate similar cohort, we mapped the BPD-associated changes in the OS proteome (Cohort 2; N=17 infants including 8 with BPD). RESULTS: In samples collected during the first month of life, we identified 607 proteins unique to OS, 327 proteins unique to TA, and 687 overlapping proteins belonging to pathways involved in immune effector processes, neutrophil degranulation, leukocyte mediated immunity, and metabolic processes. Furthermore, we identified 37 OS proteins that showed significantly differential abundance between BPD cases and controls: 13 were associated with metabolic and immune dysregulation, 10 of which (eg, SERPINC1, CSTA, BPI) have been linked to BPD or other prematurity-related lung disease based on blood or TA investigations, but not OS. CONCLUSION: OS are a noninvasive, easily accessible alternative to TA and amenable to high-throughput proteomic analysis in preterm newborns. OS samples hold promise to yield actionable biomarkers of BPD development, particularly for prospective categorization of at-risk infants for timely clinical trial enrollment with novel therapies.

Potenciales evocados auditivos de tronco en neonatos nacidos a gran altitud / Brainstem auditory evoked potentials in newborn infants born in a high-altitude area

Introducción. Una forma no invasiva y segura de evaluar los parámetros neurofisiológicos en recién nacidos es la evaluación de los potenciales evocados auditivos del tronco encefálico (PEAT). Objetivo. Evaluar las latencias e intervalos de ondas de los PEAT en neonatos sanos nacidos a gran altitud (Cusco, 3399 msnm). Población y métodos. Estudio transversal y prospectivo. Se incluyeron neonatos menores a 14 días de vida, dados de alta a menos de 7 días de nacidos, evaluados para determinar los valores de los PEAT a intensidades sonoras de 70 dB, 80 dB y 90 dB. Se incluyeron las variables edad gestacional, peso al nacer, tipo de parto. Se calcularon las diferencias de las medianas de las latencias e intervalos de las ondas según edad gestacional y peso al nacer. Resultados. Se evaluaron 96 neonatos (17 pretérminos). Las medianas de las latencias de las ondas I a V a 90 dB fueron las siguientes: onda I 1,56 ms; onda II 2,74 ms; onda III 4,37 ms; onda IV 5,62 ms, onda V 6,63 ms. La latencia de la onda I para 80 dB fue de 1,71 ms y para 70 dB de 1,88 ms. Los intervalos para las ondas (I-III), (III-V) y (I-V) fueron de 2,8 ms, 2,2 ms y 5,0 ms respectivamente, sin diferencias entre intensidades (p >0,05). La prematuridad y el bajo peso estuvieron asociados a latencias de la onda I más prolongadas (p <0,05). Conclusiones. Se presentan valores ajustados de latencias e intervalos de los PEAT en neonatos nacidos a gran altitud. Se identificó que, a distintas intensidades sonoras, se ven diferencias en las latencias de las ondas, pero no en los intervalos entre ondas.

Introduction. A non-invasive and safe way to assess neurophysiological parameters in newborn infants is the evaluation of brainstem auditory evoked potentials (BAEPs). Objective. To assess the latencies and wave intervals of BAEPs in healthy newborn infants born in a high-altitude area (Cusco, 3399 MASL). Population and methods. Cross-sectional and prospective study. Newborn infants younger than 14 days of age, discharged less than 7 days after birth, were assessed to determine BAEP values at intensities of 70 dB, 80 dB, and 90 dB. The study variables were gestational age, birth weight, and type of delivery. The median differences in wave latencies and intervals were estimated according to gestational age and birth weight. Results. A total of 96 newborn infants (17 preterm infants) were assessed. The median latencies of waves I­V at 90 dB were for wave I: 1.56 ms, wave II: 2,74 ms, wave III: 4.37 ms, wave IV: 5.62 ms, and wave V: 6.63 ms. The latency of wave I for 80 dB was 1.71 ms and for 70 dB, 1.88 ms. Wave intervals (I­III, III­V, I­V) were 2.8 ms, 2.2 ms, and 5.0 ms, respectively, without differences among intensities (p > 0.05). Prematurity and low birth weight were associated with a longer wave I latency (p < 0.05). Conclusions. Here we describe adjusted BAEP latency and interval values for newborn infants born at high altitude. At different sound intensities, we identified differences in wave latencies, but not in interwave intervals.

Factors influencing fathers' involvement in the care of hospitalized preterm newborns in Balaka, Malawi.

BACKGROUND: Malawi has one of the highest incidences of premature birth, with twice the mortality compared to full-term. Excluding fathers from preterm newborn care has negative consequences, including father feeling powerless, missed bonding opportunities with the newborn, additional strain on the mother, and negative family dynamics such as breakdown in communication, reduced trust, and strained relationships. In Malawi, there is no deliberate policy to have fathers involved in preterm care despite having high incidence of preterm birth and neonatal mortality. There is also limited literature on the factors that influence fathers' involvement in the care. The aim of the study was to explore factors influencing fathers' involvement in the care of hospitalized preterm newborns. METHODS: A descriptive qualitative study design was used, guided by Theory of planned behaviour and the model proposed by Lamb on male involvement. Sixteen in-depth interviews were conducted with fathers of preterm infants purposively and conveniently sampled in June 2021. Interviews were digitally recorded and transcribed verbatim. Data were organized and analyzed using Nvivo software and thematic analysis approach was used because the approach allows deeper understanding of the data, identification of patterns and themes, and provides rich insights into participants' experiences and perspectives. RESULTS: The barriers and facilitators that influence a father's involvement in the care of preterm newborn babies include: perceived difficulty with care activities and benefits of involvement, gender roles and socio-cultural beliefs, work and other family responsibilities, social support, baby's physical appearance/nature and health status, feedback from the baby, multiple births, and hospital's physical environment and provision of basic needs. CONCLUSION: The study found that fathers value their involvement in caring for hospitalized preterm newborns but face barriers. Evidence-based interventions like education programs, training sessions, and support groups can help fathers overcome barriers and promote better outcomes for infants and families.

Maintaining normothermia immediately after birth in preterm infants <34 weeks' gestation: A systematic review and meta-analysis.

AIM: To evaluate delivery room (DR) interventions to prevent hypothermia and improve outcomes in preterm newborn infants <34 weeks' gestation. METHODS: Medline, Embase, CINAHL and CENTRAL were searched till 22nd July 2022. Randomized controlled trials (RCTs), non-RCTs and quality improvement studies were considered. A random effects meta-analysis was performed, and the certainty of evidence was evaluated using GRADE guidelines. RESULTS: DR temperature of ≥23 °C compared to standard care improved temperature outcomes without an increased risk of hyperthermia (low certainty), whereas radiant warmer in servo mode compared to manual mode decreased mean body temperature (MBT) (moderate certainty). Use of a plastic bag or wrap (PBW) improved normothermia (low certainty), but with an increased risk of hyperthermia (moderate certainty). Plastic cap improved normothermia (moderate certainty) and when combined with PBW improved MBT (low certainty). Use of a cloth cap decreased moderate hypothermia (low certainty). Though thermal mattress (TM) improved MBT, it increased risk of hyperthermia (low certainty). Heated-humidified gases (HHG) for resuscitation decreased the risk of moderate hypothermia and severe intraventricular hemorrhage (very low to low certainty). None of the interventions was shown to improve survival, but sample sizes were insufficient. CONCLUSIONS: DR temperature of ≥23 °C, radiant warmer in manual mode, use of a PBW and a head covering is suggested for preterm newborn infants <34 weeks' gestation. HHG and TM could be considered in addition to PBW provided resources allow, in settings where hypothermia incidence is high. Careful monitoring to avoid hyperthermia is needed.

Brainstem auditory evoked potentials in newborn infants born in a high-altitude area. / Potenciales evocados auditivos de tronco en neonatos nacidos a gran altitud.

Introduction. A non-invasive and safe way to assess neurophysiological parameters in newborn infants is the evaluation of brainstem auditory evoked potentials (BAEPs). Objective. To assess the latencies and wave intervals of BAEPs in healthy newborn infants born in a high-altitude area (Cusco, 3399 MASL). Population and methods. Cross-sectional and prospective study. Newborn infants younger than 14 days of age, discharged less than 7 days after birth, were assessed to determine BAEP values at intensities of 70 dB, 80 dB, and 90 dB. The study variables were gestational age, birth weight, and type of delivery. The median differences in wave latencies and intervals were estimated according to gestational age and birth weight. Results. A total of 96 newborn infants (17 preterm infants) were assessed. The median latencies of waves I-V at 90 dB were for wave I: 1.56 ms, wave II: 2,74 ms, wave III: 4.37 ms, wave IV: 5.62 ms, and wave V: 6.63 ms. The latency of wave I for 80 dB was 1.71 ms and for 70 dB, 1.88 ms. Wave intervals (I-III, III-V, I-V) were 2.8 ms, 2.2 ms, and 5.0 ms, respectively, without differences among intensities (p > 0.05). Prematurity and low birth weight were associated with a longer wave I latency (p < 0.05). Conclusions. Here we describe adjusted BAEP latency and interval values for newborn infants born at high altitude. At different sound intensities, we identified differences in wave latencies, but not in interwave intervals.

Introducción. Una forma no invasiva y segura de evaluar los parámetros neurofisiológicos en recién nacidos es la evaluación de los potenciales evocados auditivos del tronco encefálico (PEAT). Objetivo. Evaluar las latencias e intervalos de ondas de los PEAT en neonatos sanos nacidos a gran altitud (Cusco, 3399 msnm). Población y métodos. Estudio transversal y prospectivo. Se incluyeron neonatos menores a 14 días de vida, dados de alta a menos de 7 días de nacidos, evaluados para determinar los valores de los PEAT a intensidades sonoras de 70 dB, 80 dB y 90 dB. Se incluyeron las variables edad gestacional, peso al nacer, tipo de parto. Se calcularon las diferencias de las medianas de las latencias e intervalos de las ondas según edad gestacional y peso al nacer. Resultados. Se evaluaron 96 neonatos (17 pretérminos). Las medianas de las latencias de las ondas I a V a 90 dB fueron las siguientes: onda I 1,56 ms; onda II 2,74 ms; onda III 4,37 ms; onda IV 5,62 ms, onda V 6,63 ms. La latencia de la onda I para 80 dB fue de 1,71 ms y para 70 dB de 1,88 ms. Los intervalos para las ondas (I-III), (III-V) y (I-V) fueron de 2,8 ms, 2,2 ms y 5,0 ms respectivamente, sin diferencias entre intensidades (p >0,05). La prematuridad y el bajo peso estuvieron asociados a latencias de la onda I más prolongadas (p <0,05). Conclusiones. Se presentan valores ajustados de latencias e intervalos de los PEAT en neonatos nacidos a gran altitud. Se identificó que, a distintas intensidades sonoras, se ven diferencias en las latencias de las ondas, pero no en los intervalos entre ondas.

SELENOP rs3877899 Variant Affects the Risk of Developing Advanced Stages of Retinopathy of Prematurity (ROP).

The significance of selenoproteins for the incidence of prematurity and oxidative-damage-related diseases in premature newborns is poorly understood. The latter are at risk for ROP as well as BPD, IVH, PDA, RDS, and NEC, which is particularly high for newborns with extremely low gestational age (ELGA) and extremely low birth weight (ELBW). This study evaluates the hypothesis that variation in the selenoprotein-encoding genes SELENOP, SELENOS, and GPX4 affects the risk of ROP and other comorbidities. The study included infants born ≤ 32 GA, matched for onset and progression of ROP into three groups: no ROP, spontaneously remitting ROP, and ROP requiring treatment. SNPs were determined with predesigned TaqMan SNP genotyping assays. We found the association of the SELENOP rs3877899A allele with ELGA (defined as <28 GA), ROP requiring treatment, and ROP not responsive to treatment. The number of RBC transfusions, ELGA, surfactant treatment, and coexistence of the rs3877899A allele with ELGA were independent predictors of ROP onset and progression, accounting for 43.1% of the risk variation. In conclusion, the SELENOP rs3877899A allele associated with reduced selenium bioavailability may contribute to the risk of ROP and visual impairment in extremely preterm infants.

A comparative study of the effects of Kangaroo care by mothers and maternal grandmothers on the vital signs of hospitalized preterm newborns: a randomized controlled clinical trial study.

BACKGROUND: Kangaroo care (KC) is an effective technique to prevent injury in newborns due to prematurity and hospitalization. Mothers of preterm newborns experience their own set of physical and mental problems. Such circumstances call for another family member to take care of the newborn. This study compared the effect of KC by mothers and maternal grandmothers on the vital signs of preterm newborns. METHODS: This parallel randomized controlled trial was done at the neonatal and NICU departments of the hospital in Kuhdasht in Iran. Eighty preterm neonates were selected through convenience sampling according to the eligibility criteria, then by stratified block randomization allocated to two groups. The control group received KC from the mother, and the intervention group received KC from the maternal grandmothers on the vital signs of preterm newborns. Vital signs were assessed 15 min before, during, and after the KC as the primary outcome. The data collection tools included a demographic questionnaire and a form to record the vital signs. Vital signs were measured by a pulse oximeter, an electronic thermometer, and observation. Data were analyzed by the chi-square test, the independent t-test, and the repeated measures ANOVA. RESULTS: The vital signs of newborns in each group showed a significant difference before, during, and after receiving KC (P < 0.05). Nevertheless, the vital signs of the newborns did not differ significantly between the mother and the maternal grandmother KC groups (P > 0.05). CONCLUSION: KC by maternal grandmother may stabilize the vital signs of preterm newborns as much as when this type of care is provided by the mother. We, therefore, recommend the provision of KC by the maternal grandmother, as a support and substitute for the mother whenever she is incapable of being at the hospital and to enable the mother to rest. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20211225053516N1, March 31, 2022.

Evaluación del valor de acidez Dornic de la leche humana según el tiempo de conservación en freezer y el lugar de extracción / Assessment of Dornic acidity in breast milk based on storage time in the freezer and place of expression

Introducción. El grado de acidez Dornic (AD), medida indirecta del grado de contaminación de la leche humana cruda (LHC), proporciona información sobre la calidad de esta. Recién extraída, el valor oscila entre 1,0° y 4,0° (óptimo). Descalifica el consumo si es >8,0 °D. Se evaluó la correlación de la AD de la LHC de donantes internas (DI) y externas (DE) según el tiempo de conservación hasta la pasteurización, y se determinó la prevalencia de AD ≤4 ºD. Población y método. Estudio retrospectivo analítico. Resultados. Sobre 13 203 muestras, la AD a partir del día 14 de conservación fue menor en las donantes internas, de 2,92; (IC95% 2,69-3,15) versus 4,01 (IC95%: 3,94-4,08); p <0,001] con mayor proporción de AD ≤4 ºD (88 % en DI versus 76 % en DE); OR: 2,30 (IC95%: 1,25-4,24); p = 0,003. Coeficiente de correlación para las DI: R 2 :0; p = 1). Conclusión. La AD a partir del día 14 fue menor en DI, presentando mayor prevalencia de AD ≤ 4ºD. No existió correlación entre el tiempo de conservación y la AD en las DI.

Introduction. The degree of Dornic acidity (DA) is an indirect measure of milk contamination and quality. In freshly expressed milk, DA ranges between 1.0 and 4.0 (optimal). If DA is > 8.0 °D, it should be discarded. The correlation between DA in raw breast milk from internal donors (ID) and external donors (ED) based on storage time until pasteurization was assessed. Population and method. Retrospective, analytical study. Results. In 13 203 samples, DA was lower in IDs as of 14 days of storage: 2.92 (95% CI: 2.69­3.15) versus 4.01 (95% CI: 3.94­4.08), with a higher proportion of DA ≤ 4 °D (88% in IDs versus 76% in EDs); odds ratio: 2.30 (95% CI: 1.25­4.24). Conclusion. DA as of 14 days of storage was lower in IDs, with a higher prevalence of DA ≤ 4 °D. No correlation was observed between storage time and DA in ID samples.

Association of intrauterine growth restriction and low birth weight with acute kidney injury in preterm neonates.

BACKGROUND: Preterm birth alters nephrogenesis and reduces the total nephron number. Intrauterine growth restriction (IUGR) seems to worsen nephron loss, but only a few studies have investigated its role in neonatal kidney impairment. We investigated whether IUGR, defined as reduced estimated fetal growth and/or placental flow alterations and low birth weight z-score, increases the risk of developing acute kidney injury (AKI) in very preterm infants. METHODS: We performed a retrospective study including infants born with a birth weight (BW) ≤ 1500 g and/or gestational age (GA) ≤ 32 weeks admitted to our center between January 2016 and December 2021. Neonatal AKI was defined according to the neonatal KDIGO classification based on the decline of urine output and/or creatinine elevation. We used multivariable linear regressions to verify the association between AKI and GA, BW z-score, IUGR definition, and hemodynamically significant patent ductus arteriosus (PDA). RESULTS: We included 282 infants in the analysis, with a median (IQR) GA = 29.4 (27.4, 31.3) weeks, BW = 1150 (870, 1360) g, and BW z-score = - 0.57 (- 1.64, 0.25). AKI was diagnosed in 36 (13%) patients, and 58 (21%) had PDA. AKI was significantly associated with BW z-score (beta (std. error) = - 0.08 (0.03), p = 0.008) and severe IUGR (beta (std. error) = 0.21 (0.08), p = 0.009), after adjusting for GA and PDA. CONCLUSIONS: Our data suggest that low BW z-score and IUGR could represent adjunctive risk factors for kidney impairment in preterm babies. A higher resolution version of the Graphical abstract is available as Supplementary information.

Surfactant administration during endotracheal CPAP: Feasibility, risk factors for failure and short-term outcomes of DD-SURF.

AIM: Whereas there is agreement that surfactant should be administered without mechanical ventilation, there is still a debate concerning the optimal method. DD-SURF combines the benefits of INSURE and less invasive surfactant administration (LISA). The efficacy of this approach has not been evaluated yet. METHODS: Retrospective cohort study of all preterm newborns below 300/7 weeks gestational age admitted to the neonatal intensive care unit. Data on surfactant therapy, respiratory support during the first 96 h of life and neonatal morbidities until hospital discharge were collected from the electronic patient charts to evaluate the efficacy and safety of our approach. RESULTS: In total, 222 newborns met the inclusion criteria; 174 (78%) received surfactant in the delivery room by the DD-SURF procedure and 21 infants (10%) were not extubated after surfactant administration (Surf-and-vent group). After DD-SURF, 75% of patients did not require reintubation. Intraventricular haemorrhage and bronchopulmonary dysplasia occured more often in infants after DD-SURF failure than after successful DD-SURF. CONCLUSION: DD-SURF potentially combines the benefits of INSURE and LISA and represents a useful alternative of surfactant delivery with comparable success rates to thin-catheter surfactant administration.