Early postnatal high-dose fat-soluble enteral vitamin A supplementation for moderate or severe bronchopulmonary dysplasia or death in extremely low birthweight infants (NeoVitaA): a multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial.

BACKGROUND: Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. METHODS: This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32+0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. FINDINGS: Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. INTERPRETATION: Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. FUNDING: Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

A descriptive analysis of human milk dispensed by the Leipzig Donor Human Milk Bank for neonates between 2012 and 2019.

Background: Human milk banking has become an important aspect of Nutritional medicine. It is not just about the provision of mother's own milk (MOM) or donor human milk (DHM) in the hospital, but also a strategy to encourage breastfeeding in the clinical setting and beyond. Objective: To describe the feeding patterns of hospitalised infants including human milk dispensed by the Leipzig Donor Human Milk Bank (LMB). Design: A descriptive analysis of daily data on milk feeds dispensed by LMB for hospitalised infants distinguishing between MOM or DHM, either fresh or frozen, and raw/pasteurised milk from 2012-2019. Results: We included 2,562 infants with median hospitalisation of 23 days, for whom human milk was dispensed on median 76% of those days and other nutrition on the remaining days. Raw MOM and raw DHM comprised 52% and 8% of the dispensed milk, respectively. Dispensing exclusive DHM instead of MOM for at least one full day was required for 55% of the infants, mostly at the beginning but also later during hospitalisation. Exclusive raw DHM was dispensed on at least 1 day for 37% of the infants, in different birthweight strata <1,000 g: 10%, 1,000-1500 g: 11%, 1,500-2500 g: 13% and > 2,500 g: 3%. At discharge, MOM was dispensed for more than 60% of the infants. Conclusion: During an infant's hospital stay, LMB dispenses various human milk feeds with interspersed DHM resulting in complex intra-individual and time-variant feeding patterns. LMB dispenses raw MOM and especially raw DHM with the intention to retain the properties of human milk unlike a diet containing pasteurised DHM and/or formula. Although raw DHM comprises a small percentage of all dispensed milk, raw DHM is dispensed for a substantial portion of infants. Our results document that dispensing raw DHM, is possible in routine settings.

[Operating models and organizational structures: opportunities and challenges for human milk banking in Germany]. / Versorgungsstrukturen und Betreibermodelle: Chancen und Herausforderungen des Frauenmilchbankwesens in Deutschland.

BACKGROUND: Donor human milk is the recommended alternative for feeding preterm infants if mother's own milk is unavailable. Human milk banks collect, screen, store and distribute donated human milk according to pre-specified standard operating procedures to premature infants without mothers own milk. AIM: Herein we characterize current operating models and the structural organisation of German milk bank institutions. The analysis of current and future opportunities and challenges may support the development of a comprehensive donor milk service within Germany. MATERIAL AND METHODS: Summary of the panel discussion entitled "Operating models and organizational structures: opportunities and risks for donor human milk bank in Germany" during the 3rd Scientific Symposium of the German Human Milk Bank Initiative (FMBI), November 25th to 26th 2022, in Nuremberg, Germany. RESULTS AND DISCUSSION: Differing operator models may facilitate the use of donor human milk by incorporating unique site-specific factors, pre-existing infrastructure, and individual needs. In addition to the establishment of milk banks serving single neonatal units, high-capacity milk banks should be enabled to provide donor human milk using several hub-and-spoke systems. This may create a nationwide network for a sustainable human milk supply for preterm infants that is based on qualified breastfeeding and lactation support.

Systematic Review on Individualized Versus Standardized Parenteral Nutrition in Preterm Infants.

The need for high quality evidence is recognized for optimizing practices of parenteral nutrition (PN). The purpose of the present systematic review is to update the available evidence and investigate the effect of standardized PN (SPN) vs. individualized PN (IPN) on protein intake, immediate morbidities, growth, and long-term outcome in preterm infants. A literature search was performed on articles published in the period from 1/2015 to 11/2022 in PubMed and Cochrane database for trials on parenteral nutrition in preterm infants. Three new studies were identified. All new identified trials were nonrandomized observational trials using historical controls. SPN may increase weight and occipital frontal circumference gain and lower the value of maximum weight loss. More recent trials suggest that SPN may easily increase early protein intake. SPN may reduce the sepsis incidence, but overall, no significant effect was found. There was no significant effect of standardization of PN on mortality or stage ≥2 necrotizing enterocolite (NEC) incidence. In conclusion SPN may improve growth through higher nutrient (especially protein) intake and has no effect on sepsis, NEC, mortality, or days of PN.

Diversity and trends of human milk banking: a scoping review from 1946 to 2021.

BACKGROUND: The provision of donor human milk (DHM) through human milk banks is now widely practised globally. The study aimed to describe the current state, identify major topics and map out the emerging trends in human milk banking. METHODS: PubMed was systematically searched for publications related to DHM, with the last update on 14 May 2021, for papers published between 1946 and 2021. Titles and abstracts were screened and indexed into 8 main and 39 subcategories. A top-up search was done in April 2022, but these results have not been incorporated. RESULTS: A total of 1083 publications were identified, and more than a third (41%) were either observational or interventional studies. Predominant topics were milk type and milk composition. Almost half (49%) of the publications in the last decade were funded through government/research councils, and industry funding started shortly after links between formula and necrotising enterocolitis were published. Literature from high-income countries was six times more than publications from low-income or middle-income countries (LMICs). CONCLUSION: The diversity and trends of publications included in this scoping review ranged from descriptive studies comparing biological and compositional differences of mother's own milk, DHM and/or formula. Very few studies have investigated associations of different milk types with infant outcomes. Evidence on breastfeeding and recipient psychological health outcomes is limited. Further research should identify the appropriateness of different funding sources. Future collaborations between academics, clinicians and milk banks in LMICs should be fostered to bridge the gap that exists between DHM and access.

"Alcohol intoxication by proxy on a NICU" - a case report.

BACKGROUND: Ethanol intoxications in newborns are generally due to false preparation of formula with alcoholics or alcohol consumption by the breastfeeding mothers. Rarely, intoxications occur in hospitalized newborns, e.g., from excessive use of alcoholic hand sanitizers. We herein report a strange case of acute ethanol intoxications in our NICU. CASE PRESENTATION: An extremely premature infant (23 0/7 weeks gestational age, birthweight 580 g) suffered from repeated life-threatening events with hemodynamic compromise, apnea, and lactic acidosis while being treated in our neonatal intensive care unit (NICU). Symptomatic treatment with intravenous fluids and, if necessary, intubation and catecholamine therapy led to recovery after several hours each time. The episodes eventually turned out to be severe ethanol intoxications brought about by breast milk contaminated with ethanol. The breast milk was supplied by the infant's mother, who consumed non-trivial amounts of alcohol to build up her strength and make herself produce more milk, which was recommended to her by a family member. Additionally, she supplemented her own mother's milk with cow's milk because she was worried her baby was underserved with her milk. The mother admitted to this in intensive conversations with our team and a professional translator. CONCLUSIONS: This unique case underlines how different cultural dynamics can attribute to life-threatening events in the care of premature infants. It is important for us to emphasize that intensive communication and building a confident relationship with the parents of patients is essential to the work on NICUs. Child safeguarding issues and possibilities of intoxications have to stay in mind even in a supposedly safe space like the NICU.

Analysis of the Endogenous Peptidomes of Different Infant Formula Types and Human Milk.

Infant formula (IF) is a commonly used replacement whenever mother's own milk is not available. Most IFs are based on cow milk (powders, liquids). Alternatives, based on other sources such as goat milk or plants, exist. Independent of the source, IF production and composition are strictly regulated. Besides proteins, minerals, and lipids, milk contains a variety of endogenous peptides. Whereas the human milk peptidome has been studied intensively, the peptidomes of IFs have been mostly neglected. This study investigated the peptidomes of different types of first stage IF, including cow milk-based powders and liquids, and powdered goat milk-based IF, highlighting major similarities and differences to human milk. Extracted native peptidomes were analyzed by nanoRPC-ESI-MS/MS using two different fragmentation techniques allowing the confident identification of 1587 peptides. ß-Casein peptides dominated in all samples. Interestingly, powdered and liquid cow milk-based IFs differed in the numbers of ß- and αS1-casein peptides, indicating processing-derived variations. However, the peptidomes of cow and goat milk-based IF appeared to be more comparable to each other than to human milk. Despite an overlap in the major source proteins, many peptide sequences were different, i.e., species-specific. Remarkably, the data indicate that the human milk peptidome might be donor-specific as well.

Donor Milk Banking - Safety, Efficacy, New Methodologies.

Donor milk (DM) is of increasing interest as primary nutritional source for preterm infants. Safe access requires special infrastructure, trained staff, sophisticated algorithms, and standard operating procedures as well as quality control measures. DM has limitations like low protein content and unpredictable composition of the other macronutrients, despite fortification frequently not meeting recommendations - both of them compromising growth. The first paragraph is devoted to COVID-19 and how it impacts processes of DM banking. The following paragraphs review aspects of "pasteurization," "safety audits/donor screening," and "DM nutrient variability." In summary, (i) Holder pasteurization still is the most suitable procedure for milk banks, but high-pressure pasteurization or ultraviolet C irradiation conserve the unique properties of DM better and deserve more research to make it suitable for clinical routine. (ii) In regard to safety/screening, guidelines are valuable for safe DM bank operation, but they differ between legislations. There is a surprisingly high rate of non-disclosed donor smoking (0.3%, p > 0.05) and of adulteration of delivered DM (up to 2%, p < 0.05) not detected by standard donor screening procedures. Frequencies differ between remunerated and non-remunerated programs. (iii) Neonatal caregivers should be aware of unpredictable composition of DM. They should be trained on how these can be overcome to avoid negative impact on growth and long-term outcomes like (a) measuring and disclosing nutrient contents of delivered DM batches to customers, (b) implementing certain types of donor pooling to reduce the risk of macronutrient depleted DM, (c) additional supplementation using 0.3-0.5 g protein/100 mL seems to be reasonable, (d) adjusted fortification may help to improve growth, but is not efficient in all preterm infants, (e) target fortification seems to improve growth (and probably also neurodevelopmental index) compared to standard fortification, (f) more research and clinical studies are needed.

CSF Surfactant Protein Changes in Preterm Infants After Intraventricular Hemorrhage.

Introduction: Surfactant proteins (SP) have been shown to be inherent proteins of the human CNS and are altered during acute and chronic disturbances of CSF circulation. Aim of the study was to examine the changes of surfactant protein concentrations in CSF of preterm babies suffering from intraventricular hemorrhage. Patients and Methods: Consecutive CSF samples of 21 preterm infants with intraventricular hemorrhages (IVH) and posthemorrhagic hydrocephalus (PHHC) were collected at primary intervention, after 5-10 days and at time of shunt insertion ~50 days after hemorrhage. Samples were analyzed for surfactant proteins A, B, C, and G by ELISA assays and the results were compared to 35 hydrocephalus patients (HC) without hemorrhage and 6 newborn control patients. Results and Discussion: Premature patients with IVH showed a significant elevation of surfactant proteins SP-A, C, and G compared to HC and control groups: mean values for the respective groups were SP-A 4.19 vs. 1.08 vs. 0.38 ng/ml. Mean SP-C 3.63 vs. 1.47 vs. 0.48 ng/ml. Mean SP-G 3.86 vs. 0.17 vs. 0.2 ng/ml. SP-A and G concentrations were slowly falling over time without reaching normal values. SP-C levels declined faster following neurosurgical interventions and reached levels comparable to those of hydrocephalus patients without hemorrhage. Conclusion: Intraventricular hemorrhages of premature infants cause posthemorrhagic CSF flow disturbance and are associated with highly significant elevations of surfactant proteins A, C, and G independent of total CSF protein concentrations.

Donor human milk programs in German, Austrian and Swiss neonatal units - findings from an international survey.

BACKGROUND: Donor human milk (DHM) has been recommended for premature infants if mothers' own milk is not available. The aim of this study was to increase the knowledge about the utilization rate and handling of DHM among neonatal units in Germany, Austria und Switzerland. METHODS: Online survey of utilization rates and handling practices of DHM of all neonatal units within Germany, Austria and Switzerland providing care for premature infants less than 32 weeks of gestation. RESULTS: DHM utilization rate of 35% is low (50/142) within those 54% of units that responded to our survey (142/261). Only 26/50 units have DHM routinely integrated into their nutritional management protocols. Lacking access and difficult procurement were cited as the main obstacles for not using DHM. However, eight out of ten respondents currently not using DHM would like to introduce DHM in their unit if available. There were differences in most aspects of DHM handling including donor recruitment and screening, testing and treatment of milk microbiota and commencement of DHM utilization. Breastmilk feeding rates were increased in units utilizing DHM compared to those not utilizing DHM. CONCLUSIONS: DHM is underutilized in most neonatal units caring for premature infants within participating countries. Lacking access to DHM represents the main barrier for utilizing DHM for premature infants.

Mutations in topoisomerase IIß result in a B cell immunodeficiency.

B cell development is a highly regulated process involving multiple differentiation steps, yet many details regarding this pathway remain unknown. Sequencing of patients with B cell-restricted immunodeficiency reveals autosomal dominant mutations in TOP2B. TOP2B encodes a type II topoisomerase, an essential gene required to alleviate topological stress during DNA replication and gene transcription, with no previously known role in B cell development. We use Saccharomyces cerevisiae, and knockin and knockout murine models, to demonstrate that patient mutations in TOP2B have a dominant negative effect on enzyme function, resulting in defective proliferation, survival of B-2 cells, causing a block in B cell development, and impair humoral function in response to immunization.

Fortification of Human Milk for Preterm Infants: Update and Recommendations of the European Milk Bank Association (EMBA) Working Group on Human Milk Fortification.

Evidence indicates that human milk (HM) is the best form of nutrition uniquely suited not only to term but also to preterm infants conferring health benefits in both the short and long-term. However, HM does not provide sufficient nutrition for the very low birth weight (VLBW) infant when fed at the usual feeding volumes leading to slow growth with the risk of neurocognitive impairment and other poor health outcomes such as retinopathy and bronchopulmonary dysplasia. HM should be supplemented (fortified) with the nutrients in short supply, particularly with protein, calcium, and phosphate to meet the high requirements of this group of babies. In this paper the European Milk Bank Association (EMBA) Working Group on HM Fortification discusses the existing evidence in this field, gives an overview of different fortification approaches and definitions, outlines the gaps in knowledge and gives recommendations for practice and suggestions for future research. EMBA recognizes that "Standard Fortification," which is currently the most utilized regimen in neonatal intensive care units, still falls short in supplying sufficient protein for some VLBW infants. EMBA encourages the use of "Individualized Fortification" to optimize nutrient intake. "Adjustable Fortification" and "Targeted Fortification" are 2 methods of individualized fortification. The quality and source of human milk fortifiers constitute another important topic. There is work looking at human milk derived fortifiers, but it is still too early to draw precise conclusions about their use. The pros and cons are discussed in this Commentary in addition to the evidence around use of fortifiers post discharge.

Processing of Donor Human Milk: Update and Recommendations From the European Milk Bank Association (EMBA).

Background: A mother's own milk (MOM) is the gold standard for the feeding and nutrition of preterm and full term infants. When MOM is not available or there is not enough, donor human milk (DHM) should be used. Milk delivered to Human Milk Banks (HMBs) should be pasteurized to inactivate viral and bacterial agents. Currently, a pasteurization process at 62.5°C for 30 min (Holder pasteurization, HoP) is recommended in all international HMBs guidelines. State of the art: It is known that HoP affects some of the nutritional and biological components of human milk. Studies have demonstrated that temperature cycle in HoP is not always controlled or calibrated. A better check of these parameters in the pasteurizers on the market today may contribute to an improvement of the quality of HM, still maintaining some of the negative effects of the heat treatment of human milk. So, food industry, and dairy industry in particular, are evaluating innovative methodologies alternative to HoP to better preserve the nutritional and biological properties of fresh human milk, while assuring at least the same microbiological safety of HoP. The most studied processing techniques include High-Temperature-Short-Time (HTST) pasteurization, High Pressure Processing (HPP), and Ultraviolet-C (UV-C) irradiation. HTST is a thermal process in which milk is forced between plates or pipes that are heated on the outside by hot water at a temperature of 72°C for 5-15 s. HPP is a non-thermal processing method that can be applied to solid and liquid foods. This technology inactivates pathogenic microorganisms by applying a high hydrostatic pressure (usually 300-800 MPa) during short-term treatments (<5-10 min). UV irradiation utilizes short-wavelength ultraviolet radiation in the UV-C region (200-280 nm), which is harmful to microorganisms. It is effective in destroying the nucleic acids in these organisms, so that their DNA is disrupted by UV radiation. Aim: The aim of this paper is to present the EMBA recommendations on processing of HM, based on the most recent results obtained with these new technologies. Conclusions: Although research on the most promising technologies that will represent an alternative to HoP (HTST, HPP, UV-C) in the future is progressing, it is now important to recognize that the consistency and quality assurance of the pasteurizers on the market today represent a fundamental component that was previously lacking in the Holder approach.

Recommendations for the Establishment and Operation of Human Milk Banks in Europe: A Consensus Statement From the European Milk Bank Association (EMBA).

Objectives: To develop recommendations from the European Milk Bank Association (EMBA) for the establishment and operation of human milk banks (HMB) in Europe. Method: A working group comprising members of the EMBA was convened in 2015 to develop Europe-wide recommendations for milk banks. Each member had experience of guideline development and/or milk banking operations. An initial survey was agreed using collated published global recommendations. A total of 108 potential recommendations were included in the survey; responders noted which were included in their national guidelines. The responses were collated, compared, and discussed and the group determined where there was consensus and where substantial or minor differences were identified. Where there was consensus or robust published evidence on which to base recommendations these were included. When there was no consensus and no clear evidence base, a statement of explanation based on collective expert opinion was agreed. Results: Published, internationally available guidelines with recommendations for human milk banks from France, Italy, and the UK, together with guidelines from Austria, Denmark, Germany, Norway, Slovakia, Spain, Sweden, and Switzerland were included as source materials. These covered: General recommendations; Donor recruitment and screening; Expression, handling, and storage of donor human milk (DHM); Pooling of DHM; Milk screening; Milk treatment (pasteurization); Delivery of DHM to recipients. Conclusions: Evidence based recommendations and consensus statements from the EMBA will now be published on the EMBA website to assist in the safe establishment and operation of HMBs throughout Europe. These have also been used to inform the chapter on human milk to be included in the 2019 edition of the Guide to the quality and safety of tissues and cells for human application, published by the European Directorate for the Quality of Medicines & HealthCare (EDQM).

Handling of Breast Milk by Neonatal Units: Large Differences in Current Practices and Beliefs.

Background: Breast milk (BM) for premature infants is subjected to multiple steps of processing, storage and distribution. These steps may influence the quality and safety of BM. Guidelines concerning the use of mother's own milk are either not available or limited to specific aspects of BM handling and are based on evidence of variable strength. This may result in diverse BM handling routines by health care professionals. Objective: We surveyed neonatal units to increase the knowledge about the current practice of BM handling routines of mother's own milk and to identify controversial aspects that could give directions for future research. Methods: An online-based questionnaire was sent to 307 different neonatal departments providing level III to level I neonatal care within Germany, Austria and Switzerland. Practices concerning screening for cytomegalovirus and BM bacteria, pasteurization, fortification, storage, workforce and the incidence of BM administration errors were surveyed. Results: A total of 152 units, 56% of contacted level III units and 51% of level II units, participated in the survey (Germany 53%, Switzerland 71%, and Austria 56%). We found differences concerning indication and method of CMV inactivation (performed by 58%), bacterial count screening (48%) and bacterial count reduction (17%) within participating units. Thirty different thresholds for bacterial BM counts were reported by 65 units, resulting in pasteurization or discarding of BM. The use of nutrient analysis (12%) and fortification regimens in addition to standard multicomponent fortifiers (58%) using either individual (93%), targeted (3%), or adjusted (4%) fortification protocols varied profoundly. There is a high variability in staff and available facilities for BM handling. 73% of units report about BM administration errors. Conclusion: There is a wide variability in most aspects of BM handling in the participating units. Despite limited evidence labor and cost intensive procedures are applied which may have an impact on BM quality.

[The value of human milk for preterm infants-overview and practical aspects]. / Der Stellenwert von Muttermilch für die gesunde Entwicklung Frühgeborener ­ aktuelle Übersicht und praktische Aspekte.

Over the last decades the immense benefit of human milk on the nutrition of preterm infants has become increasingly evident. Research has confirmed that human milk has significant advantages for the preterm infant in terms of host defense, gastrointestinal development and maturation, neurological development, reduction of necrotizing enterocolitis, retinopathy of prematurity and chronic lung disease as well as mental and physical benefits for the mother. Computing these factors into a health-cost-benefit equation, positive economic consequences for a national public health system were demonstrated.Therefore, international feeding guidelines recommend human milk to be the first choice for preterm infants, the primary source being the infant's mother. The first alternative is milk from an established donor milk bank. To meet the unique nutritional demands of preterm infants and to avoid postnatal growth restriction, human milk must be fortified with additional micro- and macronutrients. Concerns about microbial colonization and contamination and hygienic aspects concerning milk handling need to be addressed when feeding human milk to preterm infants.Early initiation and maintenance of lactation is challenging for mothers of preterm infants and their caregivers. Providing lactation support from educated staff, optimal nursing environments, and the positive attitude of an experienced NICU (neonatal intensive care unit) team will contribute to successful lactation and breastfeeding even beyond discharge of the infant.

IVH in VLBW Preterm Babies - Therapy with Recombinant Activated F VII?

Backround Intraventricular hemorrhage (IVH) remains a dangerous and frequent complication in very low birth weight (VLBW) infants. Activated factor VII (aFVII) activates the coagulation cascade and is a potential tool for stopping active bleeding, including limiting the extent of an IVH. This retrospective treatment observation compared data for infants with IVH progression treated with fresh frozen plasma (FFP) alone or with a combination of FFP and aFVII. Methods/Intervention All infants were subject to cranial ultrasonography at least twice daily. When an IVH was detected, treatment with FFP (5-20 ml/kg every 4-6 h) was commenced and the parents were informed. If the parents endorsed aFVII treatment and the IVH showed progress, aFVII (30-50 µg/kg body weight 4-6 times within 16-24 h) was given. Otherwise, infants were treated with FFP only. We compared the course of IVH between the aFVII+FFP treated infants and a control group (FFP only). Results 35 patients throughout were included in the analysis (17 control and 18 aFVII group). Demographic data was not different between groups. The progress of IVH was significantly less in the aFVII group (p<0.01). During the hospital stay, 2 of the infants in the aFVII group died compared to 4 in the control group. A posthemorrhagic hydrocephalus developed in 3 aFVII and 6 control infants. All other outcome parameters and follow-up-results 2 years after treatment did not differ significantly. Conclusion These data show that in the case of a progressing IVH, aFVII may be a candidate for limiting its extent. A prospective randomized trial is warranted.

The Cerebral Surfactant System and Its Alteration in Hydrocephalic Conditions.

INTRODUCTION: Pulmonary Surfactant reduces surface tension in the terminal airways thus facilitating breathing and contributes to host's innate immunity. Surfactant Proteins (SP) A, B, C and D were recently identified as inherent proteins of the CNS. Aim of the study was to investigate cerebrospinal fluid (CSF) SP levels in hydrocephalus patients compared to normal subjects. PATIENTS AND METHODS: CSF SP A-D levels were quantified using commercially available ELISA kits in 126 patients (0-84 years, mean 39 years). 60 patients without CNS pathologies served as a control group. Hydrocephalus patients were separated in aqueductal stenosis (AQS, n = 24), acute hydrocephalus without aqueductal stenosis (acute HC w/o AQS, n = 16) and idiopathic normal pressure hydrocephalus (NPH, n = 20). Furthermore, six patients with pseudotumor cerebri were investigated. RESULTS: SP A-D are present under physiological conditions in human CSF. SP-A is elevated in diseases accompanied by ventricular enlargement (AQS, acute HC w/o AQS) in a significant manner (0.67, 1.21 vs 0.38 ng/ml in control, p<0.001). SP-C is also elevated in hydrocephalic conditions (AQS, acute HC w/o AQS; 0.87, 1.71 vs. 0.48 ng/ml in controls, p<0.001) and in Pseudotumor cerebri (1.26 vs. 0.48 ng/ml in controls, p<0.01). SP-B and SP-D did not show significant alterations. CONCLUSION: The present study confirms the presence of SPs in human CSF. There are significant changes of SP-A and SP-C levels in diseases affecting brain water circulation and elevation of intracranial pressure. Cause of the alterations, underlying regulatory mechanisms, as well as diagnostic and therapeutic consequences of cerebral SP's requires further thorough investigations.

Media Stories on NICU Outbreaks Lead to an Increased Prescription Rate of Third-Line Antibiotics in the Community of Neonatal Care.

BACKGROUND Between 2010 and 2012, 3 outbreaks of nosocomial infections in German neonatal intensive care units (NICUs) attracted considerable public interest. Headlines on national television channels and in newspapers had important consequences for the involved institutions and a negative impact on the relationship between families and staff in many German NICUs. OBJECTIVE To determine whether NICU outbreaks reported in the media influenced provider behavior in the community of neonatal care and led to more third-line antibiotic prescribing. DESIGN Observational cohort study. METHODS To investigate secular trends, we evaluated data for very-low-birth-weight infants (VLBWIs, birth weight <1,500 g) enrolled in the German Neonatal Network (GNN) between 2009 and 2014 (N=10,253). For outbreak effects, we specifically analyzed data for VLBWIs discharged 6 months before (n=2,428) and 6 months after outbreaks (n=2,508). RESULTS The exposure of all VLBWIs to third-line antibiotics increased after outbreaks (19.4% before vs 22.5% after; P=.007). This trend particularly affected male infants (4.6% increase; P=.005) and infants with a birth weight between 1,000 and 1,499 g (3.5% increase; P=.001) In a logistic regression analysis, month of discharge as linear variable of time was associated with increased exposure to third-line antibiotics (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.009-1.014; P<.001), and discharge within the 6-month period after outbreak reports independently contributed to this long-term trend (OR, 1.14; 95% CI, 1.017-1.270; P=.024). CONCLUSIONS Media reports directly affect medical practice, eg, overuse of third-line antibiotics. Future communication and management strategies must be based on objective dialogues between the scientific community and investigative journalists. Infect Control Hosp Epidemiol 2016;37:924-930.

Does Breastmilk Influence the Development of Bronchopulmonary Dysplasia?

OBJECTIVE: To assess whether breastmilk feeding is associated with a reduced risk of bronchopulmonary dysplasia (BPD). Secondary outcome measures analyzed were retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC). STUDY DESIGN: In an ongoing multicenter cohort study, the data of 1433 very low birth weight infants born before 32 weeks of gestation and discharged in 2013 were analyzed. We compared growth and neonatal complications of infants who received breastmilk exclusively (N = 223) with those who received formula feedings exclusively (N = 239). Logistic regression models were estimated for BPD, ROP, and NEC using nutrition as an independent variable. The Firth logistic regression model and Lasso were used for sensitivity analyses. RESULTS: Exclusively breastmilk-fed infants gained less weight compared with formula-fed infants. SDS for weight decreased between birth and discharge (median (Q1-Q3): formula -0.9 (-1.4 to [-0.5]) vs breastmilk -1.1 (-1.7 to [-0.6])). Exclusive formula feeding of very low birth weight infants was associated with increased risks of BPD (OR 2.6) as well as NEC (OR 12.6) and ROP (OR 1.80) after controlling for known risk factors. CONCLUSIONS: Exclusive breastmilk feeding was associated with lower growth rates and a reduced risk of BPD as well as NEC and ROP.