Repeated intravenous doses of human umbilical cord-derived mesenchymal stromal cells for bronchopulmonary dysplasia: results of a phase 1 clinical trial with 2-year follow-up.

BACKGROUND: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). AIMS: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. METHODS: In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. RESULTS: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up. CONCLUSIONS: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.

The Effectiveness of an Oral Sensorimotor Stimulation Protocol for the Early Achievement of Exclusive Oral Feeding in Premature Infants. A Randomized, Controlled Trial.

Aims: This study is aimed to investigate the effectiveness of an oral stimulation protocol in preterm infants compared to usual care, to reduce the time for achieving safe full oral feeding.Methods: 47 preterm infants (25- 30 weeks of gestational age) were randomized into two groups. Babies of the EG (n = 24) received a 10-minute oral stimulation protocol while the CG (n = 23) received the standard care. The primary outcome were the days from the initiation of the intervention until the achievement of full oral feeding. Secondary outcomes were: days from the first day the intervention started until achieving a first oral intake of 30% in the first 5 minutes, days from the first day the intervention started until achieving a first oral intake of 100%, and days of hospitalization. A parametric survival model with Gaussian distribution was used.Results: The EG achieved full oral feeding 8.3 days before the CG (p = 0.013). EG also achieved the first oral intake of 30% in the first five minutes, 6.03 days before (p = 0.019) and of 100%, 5.88 days before (p = 0.040). EG also spent 6.9 days less hospitalized than CG (p = 0.028).Conclusion: Oral stimulation in preterm infants significantly shortens the time to achieve full oral feeding and reduces the length of hospitalization.

Intraperitoneal vancomycin in neonates during peritoneal dialysis: A case report.

WHAT IS KNOWN AND OBJECTIVE: Guidelines for prevention and treatment of peritonitis in paediatric patients recommend vancomycin. We present the clinical practice in neonates during peritoneal dialysis and evaluate dosage and serum levels of vancomycin. CASE SUMMARY: This case report describes a newborn with acute renal failure under continuous peritoneal dialysis therapy and intraperitoneal vancomycin. We report the treatment dosage and serum vancomycin levels. WHAT IS NEW AND CONCLUSION: There is great variability in the recommended dose of vancomycin for continuous peritoneal dialysis and the available clinical experience. Further investigation of dosing in children particularly in newborns, especially in loading dose, is necessary.

Do Lower Levels of Fetal Hemoglobin in Preterm Infants Relate to Oxidative Stress?

Fetal hemoglobin (HbF) has a higher affinity to oxygen than adult hemoglobin, allowing for a slower oxygen transfer to peripheral tissue, creating a microenvironment conducive to adequate fetal development in utero. However, most preterm infants receive packed red blood cell transfusions from adult donors leading to a drastic nonphysiological descent of circulating HbF. We hypothesized that this drop could enhance oxygen delivery to peripheral tissues generating a hyperoxic pro-oxidant environment. To investigate this, we assessed differences in oxidative stress biomarkers determined in urine samples in a cohort of 56 preterm infants born <32 weeks' gestation. Median oxidative stress biomarkers were compared between patients with circulating HbF above or below median HbF levels using Wilcoxon rank sum test. Oxidative stress biomarkers were significantly higher in the group of patients with lower levels of HbF. This study provides the initial evidence indicating elevated levels of oxidative stress biomarkers in preterm neonates with lower HbF levels. Based on the results, we hypothesize that HbF may contribute to preventing free radical-associated conditions during the newborn period. Antioxid. Redox Signal. 40, 453-459.

Corrigendum: Paracetamol vs. Ibuprofen in Preterm Infants With Hemodynamically Significant Patent Ductus Arteriosus: A Non-inferiority Randomized Clinical Trial Protocol.

[This corrects the article DOI: 10.3389/fped.2020.00372.].

Paracetamol vs. Ibuprofen in Preterm Infants With Hemodynamically Significant Patent Ductus Arteriosus: A Non-inferiority Randomized Clinical Trial Protocol.

Background: Currently, the first line treatment of persistent ductus arteriosus (PDA) is either indomethacin or ibuprofen. However, the potentially life-threatening side effects associated to their use have prompted physicians to look for alternative options. The incorporation of paracetamol as an alternative to ibuprofen in the management of PDA is still based on insufficient clinical evidence. Hence, more clinical trials are needed to establish a therapeutic role for paracetamol in the management of PDA that take into consideration short- and long-term safety and efficacy outcomes. Study Design: This is a non-inferiority, randomized, multicenter, double-blinded study to evaluate the efficacy, and safety of intravenous (IV) paracetamol vs. IV ibuprofen (standard treatment) for PDA in preterm patients with a gestational age ≤ 30 weeks. At baseline, patients will be randomized (1:1) to treatment with paracetamol or ibuprofen. The primary endpoint is closure of the ductus after the first treatment course. Secondary endpoints are related to effectiveness (need for a second treatment course, rescue treatment, reopening rate, time to definitive closure, need for surgical ligation), safety (early and long-term complications), pharmacokinetics, and pharmacodynamics, pharmacogenetics, pharmacoeconomics, and genotoxicity. Long-term follow-up to 24 months of corrected postnatal age will be performed using Bayley III neurodevelopmental scale. Trial Registration: ClinicalTrials.gov Identifier: NCT04037514. EudraCT: 2015-003177-14.

The Effect of Morbidity and Sex on Postnatal Growth of Very Preterm Infants: A Multicenter Cohort Study.

BACKGROUND: Extrauterine growth restriction is common in the preterm infant, and it is associated with poor neurodevelopment. Nutrition plays an important role in postnatal growth, but growth is also influenced by other factors like co-morbidity, and, also, there might be sex differences. METHODS: This is a cohort study including preterm infants < 32 weeks at birth (n = 21,825) from the Spanish Neonatal Network database. The effect of sex and morbidity (patent ductus arteriosus, bronchopulmonary dysplasia, necrotizing enterocolitis and late-onset sepsis) on weight gain as well as linear and head growth from birth to discharge/death was assessed with linear regression models adjusted by gestational age and Z-scores at birth. RESULTS: The 4 selected morbidities had an independent effect on all 6 growth parameters studied, which was greater in the case of necrotizing enterocolitis: changes in weight, length and head Z-scores were -0.60 (95% CI: -0.66 to -0.55), -0.62 (95% CI: -0.70 to -0.54) and -0.63 (95% CI: -0.71 to -0.56), respectively. Weight gain and linear growth were overall more affected than head growth. Girls lost slightly more weight Z-scores (-0.03; 95% CI: -0.06 to -0.002) than boys after adjustment by morbidity. There were no significant gender differences regarding linear and head growth velocity (cm/week), although girls lost more head Z-scores (-0.14; 95% CI: -0.18 to -0.10). CONCLUSIONS: Main co-morbidities associated with prematurity have an impact on postnatal growth. Head growth is less affected than length and weight. Girls are at slightly higher risk of postnatal weight and head restriction after adjustment by morbidity.

[Pulse oximetry screening of critical congenital heart defects in the neonatal period. The Spanish National Neonatal Society recommendation]. / Cribado de cardiopatías congénitas críticas en el periodo neonatal. Recomendación de la Sociedad Española de Neonatología.

Due to its severity, as well as the consequences of a late diagnosis, critical congenital heart defects (CCHD) represent a challenging situation, making an early diagnosis necessary and ideally before symptoms appear when circulatory collapse or death of the newborn can occur. Due to this, a prenatal and very early postnatal diagnosis is very important. Prenatal ultrasound screening and physical examination of the newborn can miss a considerable number of CCHD cases. Pulse oximetry screening has been demonstrated to be an effective, non-invasive, inexpensive, and well accepted tool in the early diagnosis of CCHD. The Spanish National Society of Neonatology, through its Standards Committee, and based on the current evidence, recommend the implementation of pulse oximetry screening of CCHD in Spain, and then to offer the best therapy possible to these newborn infants.

The Burden of Respiratory Disease in Very-Low-Birth-Weight Infants: Changes in Perinatal Care and Outcomes in a Decade in Spain.

BACKGROUND: Advances in perinatal care have led to a significant reduction in morbidity and mortality among very-low-birth-weight (VLBW) infants. Much of this progress is related to the prevention and management of respiratory disease. OBJECTIVES: To evaluate changes in perinatal care and its influence on respiratory morbidity and mortality among VLBW infants in Spain in 2 consecutive periods (2002-2006 and 2007-2011). METHODS: This is a retrospective analysis of data prospectively collected of all VLBW infants included in the Spanish SEN1500 network. Patients with major congenital anomalies, those who died in the delivery room (DR) and infants <230 or >346 weeks of gestational age (GA) were excluded. RESULTS: During the study period, out of 27,205 eligible VLBW infants, 24,598 (90.4%) met inclusion criteria. The most striking and statistically significant results found in the second period were: (i) reduction in the proportion of "outborn" patients; (ii) an increase in prenatal steroid administration; (iii) enhanced non-invasive respiratory support in the DR and NICU; (iv) reduction in invasive mechanical ventilation, surfactant administration, and steroids for bronchopulmonary dysplasia (BPD). Moreover, survival to hospital discharge increased (83.5 vs. 84.7%; p = 0.015); however, survival without BPD increased only among the most immature (230 to 266 weeks' GA) from 26.6 to 31.6% (p < 0.001). CONCLUSIONS: Enhanced adherence to international recommendations in perinatal care and a significant reduction in mortality were found during the second period. Survival without BPD increased only among the most immature. Further investigation is needed to optimize the strategies to prevent and manage respiratory disease in this group of patients.

Changes in perinatal care and outcomes in newborns at the limit of viability in Spain: the EPI-SEN Study.

BACKGROUND: Advances in perinatal care can influence morbidity and mortality in newborns at the limit of viability. Knowledge of these changes over time may help improve clinical decision making, optimize resource allocation and increase quality of care. OBJECTIVES: To evaluate the influence on morbidity and mortality of changes introduced in the perinatal care of preterm infants (22-26 weeks' gestational age, GA) in Spain between two consecutive periods (2002-2006 and 2007-2011). METHODS: An analysis of prospectively collected data in a national database network (SEN1500) was performed. All live newborn infants of 22-26 weeks' GA born in or transferred to referral centers of the SEN1500 network in the first 28 days of life were included. Perinatal interventions, clinical management, neonatal morbidity, and survival until hospital discharge were retrieved. RESULTS: A total of 5,470 newborns were included (2,533 and 2,937 in each period, respectively). The major changes introduced during the second period were as follows: (1) lower proportion of extramural births (11.0 vs. 8.9%, p = 0.01), (2) increase in antenatal steroids (69.5 vs. 80.8%, p < 0.001), (3) delivery by C-section (41.8 vs. 48.3%, p < 0.001) and (4) use of CPAP during resuscitation (7.8 vs. 20.7%, p < 0.001). Death in the delivery room decreased from 5.1 to 3.2% (p < 0.001). Survival increased from 49.9 to 57.9% (p < 0.001), and survival without major morbidity increased from 18.1 to 21.2% (p = 0.006). CONCLUSIONS: During the second period, a greater attachment to practices proven to have a beneficial impact on survival and reduction of morbidity in the extremely preterm infant was noted, and survival and survival without major morbidity increased. A more conservative approach was detected for newborns of 22 weeks' GA.

Estudio de la torsión ovárica fetal intrauterina mediante ecografía 3D / Study of the intrauterine fetal ovarian torsion by 3D echography

Los quistes ováricos fetales son la causa más frecuente de masa quística intraabdominal diagnosticada prenatalmente, con una incidencia en torno al 30 por ciento. Normalmente son un hallazgo casual en una ecografía de rutina y no se encuentran anomalías asociadas. Pueden resolverse espontáneamente o presentar complicaciones como rotura del quiste, hemorragia intraquística y torsión ovárica. Las diferentes opciones de tratamiento incluyen el manejo conservador, la punción con aspiración del quiste antenatal o neonatal o la quistectomía laparoscópica o por laparotomía. Tras su diagnóstico se recomiendan estudios ecográficos seriados, donde nos será de utilidad la ecografía 3D, ya que esta modalidad de ecografía nos permitirá reconstruir en tres planos el aparato reproductor femenino y estudiar con detalle numerosas patologías tanto uterinas como anexiales. Su uso en combinación con la ecografía Doppler mejora sustancialmente el diagnóstico precoz de las tumoraciones ginecológicas.

Fetal ovarian cysts are the most common cause of prenatally diagnosed intra-abdominal cystic mass, with an incidence around 30 percent. They are usually an incidental finding on a routine ultrasound and anomalies are not associated. They may be resolved spontaneously or lead to complications such as cyst rupture, intracystic hemorrhage and ovarian torsión. Treatment options include conservative management, antenatal or neonatal cyst aspiration, laparoscopic cystectomy and laparotomy. Afterthe diagnosis, serial ultrasound studies are recommended, 3D ultrasound will be useful for us, since this form of ultrasound allows us to reconstruct in three planes the female reproductive system and study in detail a number of both uterine and adnexal pathology. Its use in combination with Doppler ultrasonography improves significantly the early diagnosis of gynecologic tumors.