Real-world study in infants fed with an infant formula with two human milk oligosaccharides / Estudio en condiciones reales de lactantes alimentados con una fórmula infantil con dos oligosacáridos de leche humana

INTRODUCTION: human milk oligosaccharides (HMOs) are an important component of human milk supporting the development of a balanced intestinal microbiota and immune protection in breastfed infants. Randomized controlled trials (RCTs) have demonstrated that infant formulas supplemented with the HMOs 2'-fucosyllactose (2'FL) and lacto-N-neotetraose (LNnT) are safe, well-tolerated, and support normal growth. This Real-World Evidence (RWE) study aimed to evaluate growth and tolerance in infants consuming a formula supplemented with 1 g/L of 2'FL and 0.5 g/L of LNnT, and included a mixed-feeding group never studied before in RCTs. Participants and methods: this open-label, prospective study was conducted at six centers in Spain, and included healthy, exclusively breastfed infants (BF group), an exclusively formula-fed group (FF) who received a milk-based formula with 2' FL and LNnT, and a group mixed fed with both formula and human milk (MF), for 8 weeks. Co-primary outcomes were growth (anthropometry) and gastrointestinal tolerance (Infant Gastrointestinal Symptom Questionnaire, IGSQ). Secondary outcomes included formula satisfaction and adverse events (AEs). RESULTS: 159 infants completed the study (66 FF, 48 MF, and 45 BF). Mean z-scores for growth were similar between all groups and within ± 0.5 of WHO medians at week 8. Composite IGSQ scores demonstrated low GI distress in all groups, with no significant group differences at baseline, week 4, or week 8. Incidence of AEs was low overall, and comparable across groups. CONCLUSIONS: in this RWE study examining a HMO-supplemented infant formula, growth and tolerance outcomes were similar to RCT findings, supporting the effectiveness of this early feeding option

INTRODUCCIÓN: los oligosacáridos de la leche materna (HMO) contribuyen a desarrollar la inmunoprotección y la microbiota intestinal. Los ensayos aleatorizados (RCT) han demostrado que las fórmulas enriquecidas con 2'fucosilactosa (2'FL) y lacto-N-neotetraosa (LNnT) son seguras, bien toleradas y favorecen el crecimiento. El objetivo de este estudio ha sido valorar el crecimiento, la seguridad y la tolerancia digestiva en lactantes alimentados con una fórmula enriquecida con 1 g/L de 2'FL y 0,5 g/L de LNnT, con datos de la vida real (RWE), incluyendo un grupo de alimentación mixta no estudiado antes en los RCT. Participantes y métodos: estudio prospectivo abierto en seis hospitales españoles que incluyó lactantes sanos alimentados con leche materna (BF), con fórmula enriquecida en 2'FL y LNnT (FF) o con mezcla de ambas (MF), durante ocho semanas. Se valoraron el crecimiento (antropometría), la tolerancia gastrointestinal (cuestionario IGSQ) y los acontecimientos adversos. RESULTADOS: 159 lactantes completaron el estudio (66, 48 y 45, en los grupos FF, MF y BF, respectivamente). Las puntuaciones Z antropométricas a la semana 8 fueron similares entre los grupos y se hallaron dentro del rango de ± 0,5 de la normalidad. Las puntuaciones IGSQ compuestas mostraron un bajo malestar digestivo, sin diferencias significativas entre los grupos, al inicio y en las semanas 4 y 8. La incidencia de eventos adversos fue baja y comparable entre los grupos. CONCLUSIONES: en este estudio RWE que evaluó una fórmula para lactantes enriquecida en HMO, los resultados sobre el crecimiento, la tolerancia y la seguridad fueron similares a los obtenidos en los RCT, respaldando su eficacia como alimentación temprana opcional

Real-world study in infants fed with an infant formula with two human milk oligosaccharides.

Introduction: Introduction: human milk oligosaccharides (HMOs) are an important component of human milk supporting the development of a balanced intestinal microbiota and immune protection in breastfed infants. Randomized controlled trials (RCTs) have demonstrated that infant formulas supplemented with the HMOs 2'-fucosyllactose (2'FL) and lacto-N-neotetraose (LNnT) are safe, well-tolerated, and support normal growth. This Real-World Evidence (RWE) study aimed to evaluate growth and tolerance in infants consuming a formula supplemented with 1 g/L of 2'FL and 0.5 g/L of LNnT, and included a mixed-feeding group never studied before in RCTs. Participants and methods: this open-label, prospective study was conducted at six centers in Spain, and included healthy, exclusively breastfed infants (BF group), an exclusively formula-fed group (FF) who received a milk-based formula with 2' FL and LNnT, and a group mixed fed with both formula and human milk (MF), for 8 weeks. Co-primary outcomes were growth (anthropometry) and gastrointestinal tolerance (Infant Gastrointestinal Symptom Questionnaire, IGSQ). Secondary outcomes included formula satisfaction and adverse events (AEs). Results: 159 infants completed the study (66 FF, 48 MF, and 45 BF). Mean z-scores for growth were similar between all groups and within ± 0.5 of WHO medians at week 8. Composite IGSQ scores demonstrated low GI distress in all groups, with no significant group differences at baseline, week 4, or week 8. Incidence of AEs was low overall, and comparable across groups. Conclusions: in this RWE study examining a HMO-supplemented infant formula, growth and tolerance outcomes were similar to RCT findings, supporting the effectiveness of this early feeding option.

Introducción: Introducción: los oligosacáridos de la leche materna (HMO) contribuyen a desarrollar la inmunoprotección y la microbiota intestinal. Los ensayos aleatorizados (RCT) han demostrado que las fórmulas enriquecidas con 2'fucosilactosa (2'FL) y lacto-N-neotetraosa (LNnT) son seguras, bien toleradas y favorecen el crecimiento. El objetivo de este estudio ha sido valorar el crecimiento, la seguridad y la tolerancia digestiva en lactantes alimentados con una fórmula enriquecida con 1 g/L de 2'FL y 0,5 g/L de LNnT, con datos de la vida real (RWE), incluyendo un grupo de alimentación mixta no estudiado antes en los RCT. Participantes y métodos: estudio prospectivo abierto en seis hospitales españoles que incluyó lactantes sanos alimentados con leche materna (BF), con fórmula enriquecida en 2'FL y LNnT (FF) o con mezcla de ambas (MF), durante ocho semanas. Se valoraron el crecimiento (antropometría), la tolerancia gastrointestinal (cuestionario IGSQ) y los acontecimientos adversos. Resultados: 159 lactantes completaron el estudio (66, 48 y 45, en los grupos FF, MF y BF, respectivamente). Las puntuaciones Z antropométricas a la semana 8 fueron similares entre los grupos y se hallaron dentro del rango de ± 0,5 de la normalidad. Las puntuaciones IGSQ compuestas mostraron un bajo malestar digestivo, sin diferencias significativas entre los grupos, al inicio y en las semanas 4 y 8. La incidencia de eventos adversos fue baja y comparable entre los grupos. Conclusiones: en este estudio RWE que evaluó una fórmula para lactantes enriquecida en HMO, los resultados sobre el crecimiento, la tolerancia y la seguridad fueron similares a los obtenidos en los RCT, respaldando su eficacia como alimentación temprana opcional.

Relevance of urinary S100B protein levels as a short-term prognostic biomarker in asphyxiated infants treated with hypothermia.

The initial diagnosis of neonatal hypoxic-ischemic encephalopathy is based on nervous system clinical manifestations. The use of biomarkers to monitor brain injury and evaluate neuroprotective effects allows early intervention and treatment. This study was designed to determine the short-term prognostic significance of urinary S100B calcium-binding protein (S100B) in asphyxiated newborns treated with hypothermia.An observational prospective study was conducted over a period of 5 years in 31 newborns with hypoxic-ischemic encephalopathy who received therapeutic hypothermia. The patients were divided into 2 groups: Group A (13 newborns with a normal neurological examination before discharge) and Group B (18 newborns who died during admission or had an abnormal neurologic examination before discharge). Urinary S100B was the main variable, serum S100B and neuron-specific enolase (NSE) were considered as secondary variables, and all of them were assessed on the first 3 days of life. The newborns were subsequently divided into groups with normal and abnormal electrophysiological and imaging findings.Mean urinary S100B levels were significantly higher in group B than group A on day 1 (10.58 ±â€Š14.82 vs 4.65 ±â€Š9.16 µg/L, P = .031) and day 2 (5.16 ±â€Š7.63 vs 0.88 ±â€Š2.53, P = .002). The optimal cutoff for urinary S100B on day 1 was >1.11 µg/L of (sensitivity, 100%; specificity 60%) for the prediction of neonatal death and < 0.66 µg/L (sensitivity 83% and specificity 70%) for the prediction of a normal neurological examination before discharge. It was not possible to calculate cutoffs with a similar accuracy for serum S100B or NSE. Urinary S100B on day 1 was higher in patients with abnormal magnetic resonance imaging findings (7.89 ±â€Š8.09 vs 4.49 ±â€Š9.14, P = .039) and abnormal positron emission tomography findings (8.60 ±â€Š9.29 vs 4.30 ±â€Š8.28, P = .038). There were no significant differences in S100B levels between patients with normal and abnormal electroencephalography results.Urinary S100B measured in the first days of life can predict neonatal death and short-term prognosis in asphyxiated newborns treated with hypothermia. The method is convenient, noninvasive, and has a higher sensitivity and specificity than measurement of serum S100B or NSE.

Taquicardia supraventricular en recién nacidos y su asociación con reflujo gastroesofágico / Supraventricular tachycardia in newborns and its association with gastroesophageal reflux disease

Introducción: La taquicardia supraventricular (TSV) es la arritmia más común en el periodo neonatal, sin embargo, su asociación con otros procesos desencadenantes no está bien establecida. El objetivo de este estudio es analizar la posible relación entre TSV neonatal y el reflujo gastroesofágico (RGE), por ser una dolencia relacionada recientemente con las arritmias auriculares. Material y métodos: Se realizó un estudio descriptivo longitudinal retrospectivo de recién nacidos que fueron diagnosticados de TSV en una unidad neonatal de nivel III, durante un período de 5 años, valorando los aspectos morfológicos, la sintomatología asociada y los tratamientos recibidos. Se estudió su asociación con el RGE y la repercusión de este sobre la TSV. Resultados: Dieciocho pacientes (1,2 de cada 1.000 recién nacidos) fueron diagnosticados de TSV. El 50% asociaban RGE con repercusión clínica (p = 0,01) y todos ellos recibieron tratamiento farmacológico. El tiempo medio de control de la TSV sin RGE desde el diagnóstico fue de 6 días (IC 95%: 2,16-9,84, con una mediana de 3) y de 7,6 días cuando estuvieron las 2 dolencias asociadas (IC 95%: 4,14-10,9, mediana de 7) (valor p = 0,024). Conclusiones: Los pacientes con TSV en el período neonatal tienen frecuentemente RGE, y esta asociación genera una mayor dificultad para el control de la taquicardia. El reflujo podría actuar como desencadenante o perpetuante de la arritmia, por eso es importante buscar y tratar el RGE en los recién nacidos con TSV (AU)

Introduction: Supraventricular tachycardia (SVT) is the most common arrhythmia in the neonatal period, but its association with other triggering processes is not well established. The aim of the study was to analyse the possible relationship between neonatal SVT and gastroesophageal reflux disease (GERD), a condition which was recently linked to atrial arrhythmias. Material and methods: A retrospective longitudinal descriptive study was conducted over a period of 5 years on newborns who were diagnosed with SVT in a level III neonatal unit, assessing morphological aspects, associated symptoms, and treatments received. Its association with GERD and the impact of this on SVT was studied. Results: Eighteen patients (1.2 per 1000 newborns) were diagnosed with SVT. Fifty percent of them were combined with clinically significant GERD (P=.01), and all of them received drug treatment. The average time of control of SVT without GERD since diagnosis was 6 days (95% CI: 2.16-9.84, with a median of 3) and 7.6 days when both pathologies were present (95% CI: 4.14-10.9, with a median of 7) (P=.024). Conclusions: Patients with SVT in the neonatal period frequently have GERD, and this combination leads to more difficulty in controlling the tachycardia. The reflux could act as a trigger or perpetuator of arrhythmia, therefore it is important to find and treat GERD in infants with SVT (AU)

[Supraventricular tachycardia in newborns and its association with gastroesophageal reflux disease]. / Taquicardia supraventricular en recién nacidos y su asociación con reflujo gastroesofágico.

INTRODUCTION: Supraventricular tachycardia (SVT) is the most common arrhythmia in the neonatal period, but its association with other triggering processes is not well established. The aim of the study was to analyse the possible relationship between neonatal SVT and gastroesophageal reflux disease (GERD), a condition which was recently linked to atrial arrhythmias. MATERIAL AND METHODS: A retrospective longitudinal descriptive study was conducted over a period of 5years on newborns who were diagnosed with SVT in a level III neonatal unit, assessing morphological aspects, associated symptoms, and treatments received. Its association with GERD and the impact of this on SVT was studied. RESULTS: Eighteen patients (1.2 per 1000 newborns) were diagnosed with SVT. Fifty percent of them were combined with clinically significant GERD (P=.01), and all of them received drug treatment. The average time of control of SVT without GERD since diagnosis was 6 days (95% CI: 2.16-9.84, with a median of 3) and 7.6 days when both pathologies were present (95% CI: 4.14-10.9, with a median of 7) (P=.024). CONCLUSIONS: Patients with SVT in the neonatal period frequently have GERD, and this combination leads to more difficulty in controlling the tachycardia. The reflux could act as a trigger or perpetuator of arrhythmia, therefore it is important to find and treat GERD in infants with SVT.

Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; a randomized controlled trial.

BACKGROUND & AIMS: Nutritional supplementation with polyunsaturated fatty acids is important in preterm infants neurodevelopment, but it is not known if the omega-6/omega-3 ratio affects this process. This study was designed to determine the effects of a balanced contribution of arachidonic acid in very preterm newborns fed with formula milk. METHODS: This was a randomized trial, in which newborns <1500 g and/or <32 weeks gestational age were assigned to one of two groups, based on the milk formula they would receive during the first year of life. Initially, 60 newborns entered the study, but ultimately, group A was composed of 24 newborns, who were given formula milk with an ω-6/ω-3 ratio of 2/1, and Group B was composed of 21 newborns, given formula milk with an ω-6/ω-3 ratio of 1/1. The infants were followed up for two years: growth, visual-evoked potentials, brainstem auditory-evoked potentials, and plasma fatty acids were periodically measured, and psychomotor development was assessed using the Brunet Lézine scale at 24 months corrected age. A control group, for comparison of Brunet Lézine score, was made up of 25 newborns from the SEN1500 project, who were fed exclusively with breast milk. RESULTS: At 12 months, arachidonic acid values were significantly higher in group A than in group B (6.95 ± 1.55% vs. 4.55 ± 0.78%), as were polyunsaturated fatty acids (41.02 ± 2.09% vs. 38.08 ± 2.32%) achieved a higher average. Group A achieved a higher average Brunet Lézine score at 24 months than group B (99.9 ± 9 vs. 90.8 ± 11, p =0.028). The Brunet Lézine results from group A were compared with the control group results, with very similar scores registered between the two groups (99.9 ± 9 vs. 100.5 ± 7). There were no significant differences in growth or evoked potentials between the two formula groups. CONCLUSIONS: Very preterm infants who received formula with an ω-6/ω-3 ratio of 2/1 had higher blood levels of essential fatty acids during the first year of life, and better psychomotor development, compared with very preterm newborns who consumed formula with an ω-6/ω-3 of 1/1. Therefore, formula milk with an arachidonic acid quantity double that of docosahexaenoic acid should be considered for feeding very preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02503020.