Synthetic Surfactant CHF5633 Compared with Poractant Alfa in the Treatment of Neonatal Respiratory Distress Syndrome: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial.

OBJECTIVE: To compare efficacy and safety of a new synthetic surfactant, CHF5633, enriched with surfactant proteins, SP-B and SP-C peptide analogues, with porcine surfactant, poractant alfa, for the treatment of respiratory distress syndrome in infants born preterm. STUDY DESIGN: Neonates born preterm on respiratory support requiring fraction of inspired oxygen (FiO2) ≥0.30 from 240/7 to 266/7 weeks and FiO2 ≥0.35 from 270/7 to 296/7 weeks of gestation to maintain 88%-95% oxygen saturation were randomized to receive 200 mg/kg of CHF5633 or poractant alfa. If necessary, redosing was given at 100 mg/kg. Efficacy end points were oxygen requirement (FiO2, respiratory severity score [FiO2 × mean airway pressure]) in the first 24 hours, 7 and 28 days, discharge home, and/or 36 weeks of postmenstrual age; mortality and bronchopulmonary dysplasia at 28 days and 36 weeks of PMA. Adverse events and immunogenicity were monitored for safety. RESULTS: Of the 123 randomized neonates, 113 were treated (56 and 57 in CHF5633 and poractant alfa groups, respectively). In both arms, FiO2 and respiratory severity score decreased from baseline at all time points (P < .001) with no statistically significant differences between groups. Rescue surfactant use (19 [33.9%] vs 17 [29.8%]), bronchopulmonary dysplasia (31 [55.4%] and 32 [56.1%]), and mortality at day 28 (4 [7.1%] and 3 [5.3%]) were similar in the CHF5633 and poractant alfa groups, respectively. In 2 (3.4%) and 1 (1.7%) neonates, adverse drug reactions were reported in CHF5633 and poractant alfa groups, respectively. No immunogenicity was detected. CONCLUSIONS: Treatment with CHF5633 showed similar efficacy and safety as poractant alfa in neonates born preterm with moderate-to-severe respiratory distress syndrome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02452476.

NICU Graduate Reunion: "A Celebration of Life".

BACKGROUND: Few understand the experience of having an infant in the neonatal intensive care unit (NICU). This article provides a discussion about the importance of an annual reunion for former NICU infants, their families, and neonatal staff. PURPOSE: The purpose of this article is to explain the impact of the NICU reunion on families and neonatal healthcare providers and describe the experience of organizing this reunion over the past 20 years. METHODS: This is a description of how a NICU reunion was organized at a regional neonatal center. Graphic-designed invitations were e-mailed to NICU graduates, who previously agreed to being contacted, 2 months prior to the reunion date. Social media were utilized to publicize the event on the hospital's Web site. RESULTS: At the reunion, parents and families introduced their NICU graduate to the neonatal staff who cared for them while hospitalized. Sometimes staff found it difficult to recognize the NICU graduates, who were toddlers or older. Parents were relaxed, expressing their appreciation for care received. IMPLICATIONS FOR PRACTICE: The impact of seeing an infant, born at 24 weeks, now walking, talking, and running cultivates pride in the NICU healthcare team. The reunion adds a positive dimension to the work of NICU caregivers. Parents look forward to attending the reunion to reconnect with NICU staff and other NICU parents. IMPLICATIONS FOR RESEARCH: Directions for future study include a comparison of staff and families who attend the NICU reunion and those who do not, by using a survey or online evaluation tool, to improve future reunions.

Babies born with gastroschisis and followed up to the age of six years faced long-term morbidity and impairments.

AIM: The aims of this Argentinian study were to describe and analyse the outcomes of a continuous interdisciplinary follow-up programme of patients with gastroschisis. METHODS: This was a prospective, longitudinal study of babies with gastroschisis admitted from 1 November 2003 to 31 October 2014, and this paper presents results at one, three and six years of age. Matched-pairs analyses were carried out when they were one and six. RESULTS: We enrolled 62 babies and assessed 52 at one year of age, 34 at three years and 17 at six years. This showed that 63% had mental health problems and 5% had recurrent wheezing. Normal outcomes at one, three and six years were growth (80%, 85% and 80%), neurology-psychomotor development index (64%, 50% and 82%), audiology (100%, 76% and 76%), vision (98%, 94% and 89%) and language (55%, 62% and 65%). The rehospitalisation rates were 30%, 0.3% and zero, and the surgical re-intervention rates were 9%, 0.3% and 12%. Matched-pairs analysis showed no significant differences between outcomes at the ages of one and six. CONCLUSION: Babies born with gastroschisis were at risk for long-term morbidity and impairments, according to follow-up assessments at the ages of one, three and six years.

Using a novel laminar flow unit provided effective total body hypothermia for neonatal hypoxic encephalopathy.

AIM: This was a clinical observational trial on a laminar flow device that provides total body hypothermia for infants with hypoxic ischaemic encephalopathy (HIE). METHODS: We enrolled infants born at up to 35 weeks of gestation, who presented with HIE within six hours of birth. Total body cooling was achieved using the neonatal laminar flow unit for 72 hours, with continuous rectal temperature servo control, isolation and humidification. Outcome measures were cerebral palsy, a Bayley II Mental Development Index score <70, hearing loss or blindness. We compared findings with previously published studies. RESULTS: We included 26 newborn infants (69% male) with a birthweight of 3.341 ± 1658 g and gestational age of 38.2 ± 3.2 weeks. The majority (62.6%) had a Sarnat HIE score of three and 38.4% had a score of two. Total body cooling (33-34°C) was achieved in 70 minutes and maintained with servo control, showing very little variability until rewarming. At 18-24 months of age, two of the 18 survivors were diagnosed with cerebral palsy and one was diagnosed with impaired hearing. CONCLUSION: The laminar flow unit proved effective in maintaining moderate total body hypothermia under well-controlled conditions, and our results were very similar to other studies.

Safe oxygen saturation targeting and monitoring in preterm infants: can we avoid hypoxia and hyperoxia?

UNLABELLED: Oxygen is a neonatal health hazard that should be avoided in clinical practice. In this review, an international team of neonatologists and nurses assessed oxygen saturation (SpO2 ) targeting in preterm infants and evaluated the potential weaknesses of randomised clinical trials. CONCLUSION: SpO2 of 85-89% can increase mortality and 91-95% can cause hyperoxia and ill effects. Neither of these ranges can be recommended, and wider intermediate targets, such as 87-94% or 88-94%, may be safer.

Target versus actual oxygenation index at initiation of inhaled nitric oxide in neonates with hypoxic respiratory failure: survey results from 128 patient cases.

BACKGROUND: Inhaled nitric oxide (iNO) is a well-established treatment for neonatal hypoxic respiratory failure (HRF). However, iNO therapy initiation criteria have not been standardized. This report describes a follow-up survey administered to neonatologists who had completed an Awareness, Trial, and Usage Survey. The objectives were to compare stated target oxygenation index (OI) versus actual OI at which iNO is initiated in respondents' patients and identify factors associated with iNO initiation at other levels. METHODS: Neonatologists provided iNO-treated HRF patient data. Target and actual OI at initiation were determined. Patient groups were stratified by actual OI deviation from target [<4; at (±3); above: 4-10, 11-20, >20; not measured]. Reasons for above-target OI were determined. RESULTS: Of 83 invited neonatologists, 26 (31%) participated, providing data for 128 patients; 85/128 patients (66%) had OI measured at initiation with neonatologist-stated mean target OI 18.8±5.8. Actual mean OI was 26.2±10.3. iNO was initiated ≤ target in 30/85 patients (35%); most [55/85 (65%)] had iNO initiated when OI was above target. Patients aged ≤1 day and those receiving a fraction of inspired oxygen (FiO2) of 1.0 for more than 1 h had highest OIs at initiation. CONCLUSIONS: Among surveyed neonatologists who treat infants with HRF with pulmonary hypertension (PH), there is a disparity between stated target versus actual OI for iNO initiation, particularly among infants <1 day old and those receiving FiO2 of 1.0 for more than 1 h. In term/near-term neonates with HRF with PH, neonatologists should consider implementing treatment protocols to ensure iNO initiation at stated target OI levels.

[Consensus on the diagnostic and therapeutic approach to pain and stress in the newborn]. / Consenso sobre el abordaje diagnóstico y terapéutico del dolor y el estrés en el recién nacido.

Pain and stress experienced by the newborn have not been addressed adequately. Infants in neonatal intensive care units often undergo painful and stressful invasive procedures, and inappropriate treatment increases morbidity and mortality. At the 5th Clinical Consensus of the Ibero-American Society of Neonatology, 32 neonatologists from the region were invited to establish recommendations for the diagnosis and treatment of neonatal pain and stress. Key themes were explored based on the best scientific evidence available in indexed databases. All attendees participated actively in a meeting in Santiago, Chile, with the objective of reaching a consensus on recommendations and conclusions. Pain and neonatal stress affect neurological development and long-term behavior and require timely diagnosis and appropriate management and treatment, including the use of drugs with an appropriate balance between effectiveness and toxicity. The Consensus emphasized the importance of assessing pain in the newborn from a multidimensional viewpoint, and provided recommendations on the indications and limitations for an individualized pharmacological therapy. The use of analgesics has precise indications but also important limitations; there is a lack of randomized studies in newborns, and adverse effects need to be considered. Nonpharmacological measures to mitigate pain were proposed. Stress management should begin in the delivery room, including maternal contact, stimulus reduction and the implementation of intervention reduction protocols. Recommendations for improving clinical practices related to neonatal pain and stress are presented.

Factors Influencing Neonatal Gut Microbiome and Health with a Focus on Necrotizing Enterocolitis.

Maturational changes in the gut start in utero and rapidly progress after birth, with some functions becoming fully developed several months or years post birth including the acquisition of a full gut microbiome, which is made up of trillions of bacteria of thousands of species. Many factors influence the normal development of the neonatal and infantile microbiome, resulting in dysbiosis, which is associated with various interventions used for neonatal morbidities and survival. Extremely low gestational age neonates (<28 weeks' gestation) frequently experience recurring arterial oxygen desaturations, or apneas, during the first few weeks of life. Apnea, or the cessation of breathing lasting 15-20 s or more, occurs due to immature respiratory control and is commonly associated with intermittent hypoxia (IH). Chronic IH induces oxygen radical diseases of the neonate, including necrotizing enterocolitis (NEC), the most common and devastating gastrointestinal disease in preterm infants. NEC is associated with an immature intestinal structure and function and involves dysbiosis of the gut microbiome, inflammation, and necrosis of the intestinal mucosal layer. This review describes the factors that influence the neonatal gut microbiome and dysbiosis, which predispose preterm infants to NEC. Current and future management and therapies, including the avoidance of dysbiosis, the use of a human milk diet, probiotics, prebiotics, synbiotics, restricted antibiotics, and fecal transplantation, for the prevention of NEC and the promotion of a healthy gut microbiome are also reviewed. Interventions directed at boosting endogenous and/or exogenous antioxidant supplementation may not only help with prevention, but may also lessen the severity or shorten the course of the disease.

Cord blood interleukin-6 as a predictor of early-onset neonatal sepsis.

AIM: To compare diagnostic accuracy in cord blood of interleukin-6 (IL-6) with C-reactive protein (CRP) as predictors of early-onset neonatal sepsis (EOS) in newborns with prenatal risk factors for infection. METHODS: During 12 months, cord blood IL-6 and CRP were measured immediately after birth in neonates with prenatal risk factors of infection. The odds of developing sepsis based on IL-6 and CRP values were calculated using likelihood ratios (LR), and their accuracy as predictors was compared by binary logistic regression. Multivariable logistic regression analyses were performed to identify independent risk factors for sepsis. RESULTS: Ten of 128 neonates (7.8%) were diagnosed with EOS confirmed with positive blood culture in five cases (3.9%). Cord blood IL-6 was a greater predictor of sepsis than CRP [ROC for IL-6 (0.88) vs. CRP (0.70)]. IL-6-positive and IL-6-negative LR [7.14 vs. -0.11] were superior to those calculated for CRP [2.86 vs. -0.51]. Chorioamnionitis and Apgar at 1 min were identified as independent risk factors for EOS. CONCLUSIONS: Cord blood IL-6 showed superior LR than CRP; therefore, it is a better predictor to initiate treatment in neonates with prenatal infectious risk factors immediately after birth.

Evolution of Preterm Infant Nutrition from Breastfeeding to an Exclusive Human Milk Diet: A Review.

The benefits of feeding human milk to human infants are well-established. Preterm infants, particularly those born with very low birthweight (VLBW; <1,500 g), are a uniquely vulnerable population at risk for serious, life-threatening complications as well as disruptions in normal growth and development that can affect their lives into adulthood. Feeding VLBW preterm infants an exclusive human milk diet (EHMD) from birth that consists of the mother's own milk or donor human milk plus a nutritional fortifier made exclusively from human milk has been associated with a reduction in morbidity and mortality and improved early growth and developmental metrics. Preliminary evidence suggests that the health benefits of adopting an EHMD (or avoiding cow milk products) early in life may last into adulthood. This review briefly summarizes the history of breastfeeding and describes the available evidence on the benefits of an EHMD among VLBW preterm infants as well as the importance of high-quality manufacturing standards for producing safe and effective human milk-based products.

Weight loss monitoring reduces the occurrence of neonatal hypernatremic dehydration in breastfeeding neonates.

Background: Excessive weight loss enhances the incidence of neonatal hypernatremic dehydration (NHD). We compared the effect of a new breastfeeding policy against an old breastfeeding policy on neonatal weight change and the incidence of NHD. Methods: This was a QA project between two sets of breastfeeding (BF) protocols for exclusively BF newborns. Under our old BF policy, a number of neonates had a significant loss of weight after birth and were admitted to the NICU due to NHD. We implemented a new BF policy that was used when a newborn loses>5% of previously recorded weight within a 24-h interval. Two groups were compared: the preintervention group (old BF policy) and postintervention group (new BF policy). Additionally, characteristics of newborns admitted to NICU were separately compared with the subgroup of pre- and post intervention dehydration groups. Results: Preintervention = 1320 and postintervention = 1450. Neonates with weight loss of ≥ 5% within the first 24-h time interval were higher in the postintervention group (19.7%) as compared to the preintervention group (10.2%) (P < .05). However, the number of infants diagnosed to have NHD was lower in the postintervention group (0.68%) than in the preintervention group (1.66%), (P < .03). Neonatal characteristics were comparable between subgroups of dehydration. Conclusion: An intervention at ≥ 5% neonatal weight loss markedly reduces the incidence of NHD-associated NICU admissions.

Stability of thyroid hormones during continuous infusion.

We investigated the stability of thyroid hormones during a mode of continuous drug infusion via polypropylene tubing using the same conditions that would be applied to treating patients in a hospital setting. The diluted thyroid hormones were prepared using aseptic technique, stored at 2-8°C (36-46°F) and tested within 24 h of preparation for stability and percent recovery from within plastic tubing. Experiments were done in duplicate with triplicate sets of readings for each assay point. Only T(4) prepared with 5% dextrose water (D5W) containing 1 mg/mL albumin remained constant, stable, predictable and accurate over time under various conditions. Other methods of preparation lost drug by adhering to the plastic containers and tubing by as much as 40% of starting concentration. T(3) recovery in the presence of 1 mg/mL of albumin was 107±2% (mean±standard error of the mean) of anticipated drug concentrations. We conclude from this series of experiments that to maintain an accurate and stable dosing of patients receiving intravenous thyroid hormones, 1 mg/mL of albumin must be added to the infusate to prevent lost on the plastic intravenous tubing.

Evaluation and clinical application of changes in thyroid hormone and TSH levels in critically ill full-term newborns.

INTRODUCTION: The term "euthyroid sick syndrome" (ESS) has been used to describe a pattern of thyroid hormone changes during the course of critical illness in adult patients without thyroid disease, often associated with reduced thyroid hormone secretion. OBJECTIVE: To describe the thyroid hormone profile in full-term newborns critically ill compared with thyroid hormone profile of healthy infants, and determine if alterations could be related to the severity of the disease and outcome. METHODS: A cross-sectional, observational, and prospective study of full-term infants admitted to the neonatal intensive care unit (NICU) of the Hospital de Pediatría J.P. Garrahan between July 2007 and April 2008. Serum T3, T4, and thyroid stimulating hormone (TSH) levels were measured at admission and severity of the disease was evaluated through SNAP, lactic acid, respiratory assistance and number of organs affected. RESULTS: Sick newborns showed significantly lower T3 and T4 levels compared with healthy infants [T3: -0.97 µg/dL (95% CI -0.89, -1.13) and T4: -4.37 µg/dL (95% CI -2.95, -5.78)]. Only 29 out of 94 (31%) infants presented a normal profile; 37 (39%) infants showed isolated low T3 levels, 20 (21%) infants had low T3 and T4 levels and eight (9%) infants had low TSH, T3, and T4. Of this latter group, five of eight (62%) children died suggesting a significantly higher risk of death for patients with low T3 associated with low T4 and TSH [Risk ratio (RR) 10.75 95% CI 3.93, 29]. CONCLUSIONS: Full-term sick newborns frequently have lower thyroid hormone levels than healthy ones. These observed thyroid hormones changes might be related to the underlying disease and could be used as a prognostic marker of the severity and fatal outcome of the patient.

[Second Clinical Consensus of the Ibero-American Society of Neonatology: hemodynamic management of newborns]. / Segundo Consenso Clínico de la Sociedad Iberoamericana de Neonatología: manejo hemodinámico del recién nacido.

This study reports on the process and results of the Second Clinical Consensus of the Ibero-American Society of Neonatology. Eighty neonatologists from 23 countries were invited to collaborate and participate in the event. Several questions of clinical-physiological importance in the hemodynamic management of newborns were addressed. Participants were divided into groups to facilitate interaction and teamwork, with instructions to respond to three to five questions by analyzing the literature and local factors. Meeting in Mar del Plata, Argentina, the Consensus Group served as a form for various presentations and discussions. In all, 54 neonatologists from 21 countries attended, with the objective of reaching a consensus on such matters as concepts and definitions of hemodynamic instability, the physiopathology of hemodynamic compromise, recommended therapy strategies, and hemodynamic monitoring. It is hoped that this international experience will serve as a useful initiative for future consensus building and reduction of the existing disparities among the countries of the Region in terms of treatment and outcomes.

What happens to 35 week infants that receive delivery room continuous positive airway pressure?

OBJECTIVE: Delivery room (DR) continuous positive airway pressure (CPAP) is increasing. Our study examined the risk for neonatal morbidities after DR CPAP in 35 week neonates. STUDY DESIGN: A retrospective study of 259 infants born at 35 weeks gestational age between January 1, 2017-December 31, 2018 at a single center. RESULTS: DR resuscitation was administered in 30.5%, with 19.7% receiving CPAP alone. Eighty percent who received DR CPAP were admitted to the NICU. DR CPAP was associated with the highest NICU admission risk, 9.3 times the risk of those without DR positive pressure, and with respiratory conditions (RDS: OR 4.22 {CI 1.46-11.51}, TTN: OR 3.30 {CI 1.36-7.64}). For the DR CPAP group, non-invasive positive pressure was administered post resuscitation in 90%. CONCLUSIONS: In our institution, 35 week infants frequently received DR CPAP. Of these infants, a majority were admitted to the NICU for respiratory disorders.