[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.

"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.

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.

[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.

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.

FUT 2 polymorphism and outcome in very-low-birth-weight infants.

BACKGROUND: To determine whether the secretor gene fucosyltransferase (FUT)2 polymorphism G428A is predictive for adverse outcomes in a large cohort of very-low-birth weight (VLBW) infants. METHODS: We prospectively enrolled 2,406 VLBW infants from the population-based multicenter cohort of the German Neonatal network cohort (2009-2011). The secretor genotype (rs601338) was assessed from DNA samples extracted from buccal swabs. Primary study outcomes were clinical sepsis, blood-culture confirmed sepsis, intracerebral hemorrhage (ICH), necrotizing enterocolitis (NEC) or focal intestinal perforation requiring surgery, and death. RESULTS: Based on the assumption of a recessive genetic model, AA individuals had a higher incidence of ICH (AA: 19.0% vs. GG/AG: 14.9%, P = 0.04) which was not significant in the additive genetic model (multivariable logistic regression analysis; allele carriers: 365 cases, 1,685 controls; OR: 1.2; 95% CI: 0.99-1.4; P = 0.06). Other outcomes were not influenced by FUT2 genotype in either genetic model. CONCLUSION: This large-scale multicenter study did not confirm previously reported associations between FUT2 genotype and adverse outcomes in preterm infants.

Continuous infusion of clonidine in ventilated newborns and infants: a randomized controlled trial.

OBJECTIVES: To assess the influence of an infusion of clonidine 1 µg/kg/hr on fentanyl and midazolam requirement in ventilated newborns and infants. DESIGN: Prospective, double-blind, randomized controlled multicenter trial. Controlled trials.com/ISRCTN77772144. SETTING: Twenty-eight level 3 German PICUs/neonatal ICUs. PATIENTS: Ventilated newborns and infants: stratum I (1-28 d), stratum II, (29-120 d), and stratum III (121 d to 2 yr). INTERVENTIONS: Patients received clonidine 1 µg/kg/hr or placebo on day 4 after intubation. Fentanyl and midazolam were adjusted to achieve a defined level of analgesia and sedation according to Hartwig score. MEASUREMENTS AND MAIN RESULTS: Two hundred nineteen infants were randomized; 212 received study medication, 69.7% were ventilated in the postoperative care and 30.3% for other reasons. Primary endpoint: consumption of fentanyl and midazolam in the 72 hours following the onset of study medication (main observation period) in the overall study population. The confirmatory analysis of the overall population showed no difference in the consumption of fentanyl and midazolam. Explorative age-stratified analysis demonstrated that in stratum I (n = 112) the clonidine group had a significantly lower consumption of fentanyl (clonidine: 2.1 ± 1.8 µg/kg/hr, placebo: 3.2 ± 3.1 µg/kg/hr; p = 0.032) and midazolam (clonidine: 113.0 ± 100.1 µg/kg/hr, placebo: 180.2 ± 204.0 µg/kg/hr; p = 0.030). Strata II (n = 43) and III (n = 46) showed no statistical difference. Sedation and withdrawal-scores were significantly lower in the clonidine group of stratum I (p < 0.001). Frequency of severe adverse events did not differ between groups. CONCLUSIONS: Clonidine 1 µg/kg/hr in ventilated newborns reduced fentanyl and midazolam demand with deeper levels of analgesia and sedation without substantial side effects. This was not demonstrated in older infants, possibly due to lower clonidine serum levels.

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).

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.

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.

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.

ATP-binding cassette member A3 (E292V) gene mutation and pulmonary morbidity in very-low-birth-weight infants.

AIM: ATP-binding cassette member A 3 (ABCA3) plays a critical role for the transport of surfactant phospholipids into the lamellar bodies of type II alveolar epithelial cells. Term infants carrying the E292V missense mutation of the gene encoding ABCA3 are likely to develop respiratory distress syndrome, and the mutation has also been linked to interstitial lung disease in paediatric patients. The aim of this study was to investigate the association of the E292V genotype with pulmonary morbidity in a large cohort of very-low-birth-weight (VLBW) infants. METHODS: We performed a genetic association study with a prospective, population-based multi-centre cohort of 3177 VLBW infants born in 16 German study centres between 2003 and 2009 (German Neonatal Network). The ABCA3 genotype was determined by restriction fragment length polymorphism-PCR in genomic DNA samples derived from buccal swabs. RESULTS: In a large cohort of 3177 VLBW infants, 11 individuals were found to be heterozygote for the E292V mutation (0.34%). After stratification according to ABCA3 genotype, no differences were noted for clinical characteristics, necessary treatments and neonatal pulmonary outcomes. CONCLUSIONS: Within the size limits of our study cohort, the ABCA3 missense mutation E292V had no remarkable effect on pulmonary outcome in VLBW infants. Present results do not rule out the possibility that E292V phenotype is associated with minor difference in the morbidity.

Tumor necrosis factor-α promoter -308 G/A polymorphism and susceptibility to sepsis in very-low-birth-weight infants.

OBJECTIVES: To determine whether the tumor necrosis factor-α -308 G/A polymorphism is associated with blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants. DESIGN: Genetic association studies. SETTING: Prospective, population-based, multicentered cohort of 1944 very-low-birth-weight infants born in 14 German study centers between 2003 and 2008 and 976 mothers, and a second prospective cohort of 926 very-low-birth-weight infants born in 2009 (German Neonatal Network). MEASUREMENTS AND MAIN RESULTS: In cohort I, 344 of 1944 (18.2%) very-low-birth-weight infants had at least one episode of blood culture-proven sepsis develop. The sepsis incidence stratified to genotype was 19.3% for G/G, 15.8% for G/A, 10.0% for A/A genotype (Cochrane-Armitage trend test: G/G vs. G/A: odds ratio, 1.32; 95% confidence interval, 1.03-1.71; G/G vs. A/A: odds ratio, 1.74; 95% confidence interval, 1.06-2.91; p = .03). There was a trend for association of tumor necrosis factor-α -308 A/G genotype with late-onset sepsis episodes (incidence: 17.2% for G/G, 12.5% for G/A, 10.0% for A/A genotype; Cochrane-Armitage trend test: G/G vs. G/A: odds ratio, 1.43; 95% confidence interval, 1.09-1.9; G/G vs. A/A: odds ratio, 2.05; 95% confidence interval, 1.19-3.56; p = .009). However, after adjustment for multiple testing, no significant associations were found. Furthermore, the genotype of the investigated 976 mothers had no impact on sepsis risk for their very-low-birth-weight infants. We additionally studied a second prospective cohort of 926 very-low-birth-weight infants and found no associations with sepsis risk. CONCLUSIONS: No association was found between the tumor necrosis factor-α -308 G/A polymorphism blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants. A recent meta-analysis demonstrated that the tumor necrosis factor-α -308 A allele is associated with higher sepsis risk in adult cohorts. Thus, potential differences between adults and infants need to be incorporated in future study designs evaluating risk profiles for sepsis.

Hoffman syndrome: New patients, new insights.

Hypogammaglobulinemia or agammaglobulinemia are major features of specific syndromes, including X-linked agammaglobulinemia and common variable immunodeficiency. However, the combination of hypogammaglobulinemia with specific dysmorphic features is less common, with only a few reported cases. One such report was a sporadic case of humoral immunodeficiency, facial dysmorphism, and limb anomalies in a young girl, later referred to as Hoffman syndrome. We report on a 7-year-old girl with almost complete loss of B cells, facial dysmorphism, and malformation of the limbs and genitalia, whose mother shows similar dysmorphic features with an attenuated version of the B-cell deficiency. We believe that all three cases described above represent the same condition. The features of the three affected individuals with Hoffman syndrome are reviewed. Further investigations in this recently recognized B-cell immunodeficiency syndrome are warranted.

Leptin in maternal serum and breast milk: association with infants' body weight gain in a longitudinal study over 6 months of lactation.

The adipokine leptin has been detected in human breast milk, but its effect on postnatal growth and development remains largely unclear. We hypothesized that leptin could affect infant's body weight gain during early lactation in the first 6 mo of life. Therefore, we evaluated leptin levels in maternal serum and breast milk of 23 healthy, lactating mothers and their neonates in a prospective, longitudinal study. Leptin concentration was quantified by a commercially available human leptin RIA. Our results showed that leptin levels in breast milk were 22-fold lower than in maternal serum, but both parameters were positively correlated to each other (r = 0.431, p = 0.001) and to maternal BMI (serum: r = 0.512, p < 0.001; milk: r = 0.298, p < 0.001) over 6 mo of lactation. A negative association was found between breast milk leptin levels during the first week after delivery and the infant weight gain from the end of the first to the sixth month (r = -0.681, p = 0.007). This suggests that milk-borne leptin provides a link between maternal body composition and infant growth and development and plays a critical role in regulating appetite and food intake during early infancy.

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.

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.

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.

Does the enteral feeding advancement affect short-term outcomes in very low birth weight infants?

BACKGROUND AND OBJECTIVES: Controversy exists regarding the optimal enteral feeding regimen of very low birth weight infants (VLBW). Rapid advancement of enteral feeding has been associated with an increased rate of necrotizing enterocolitis. In contrast, delaying enteral feeding may have unfavorable effects on nutrition, growth, and neurodevelopment. The aim is to compare the short-term outcomes of VLBW infants in tertiary care centers according to their enteral feeding advancement. PATIENTS AND METHODS: We prospectively studied the influence of center-specific enteral feeding advancement in 1430 VLBW infants recruited from 13 tertiary neonatal intensive care units in Germany on short-term outcome parameters. The centers were post hoc stratified to "rapid advancement to full enteral feeds" (median duration of advancement to full enteral feeds < or =12.5 days; 6 centers), that is, rapid advancement (RA), or "slow advancement to full enteral feeds" (median duration of advancement to full enteral feeds >12.5 days; 7 centers), that is, slow advancement (SA). RESULTS: VLBW infants born in centers with SA (n = 713) had a significantly higher rate of sepsis compared with VLBW infants born in centers with RA (n = 717), which was particularly evident for late-onset sepsis (14.0% vs 20.4%; P = 0.002). Furthermore, more central venous lines (48.6% vs 31.1%, P < 0.001) and antibiotics (92.4% vs 77.7%, P < 0.001) were used in centers with SA. CONCLUSIONS: Center differences in enteral feeding advancement occur and may have a significant impact on short-term outcomes such as nosocomial sepsis. Large, multicenter, prospective trials are required to further elucidate the optimal feeding strategy for VLBW infants.