High-frequency ventilation in preterm infants and neonates.

High-frequency ventilation (HFV) has been used as a respiratory support mode for neonates for over 30 years. HFV is characterized by delivering tidal volumes close to or less than the anatomical dead space. Both animal and clinical studies have shown that HFV can effectively restore lung function, and potentially limit ventilator-induced lung injury, which is considered an important risk factor for developing bronchopulmonary dysplasia (BPD). Knowledge of how HFV works, how it influences cardiorespiratory physiology, and how to apply it in daily clinical practice has proven to be essential for its optimal and safe use. We will present important aspects of gas exchange, lung-protective concepts, clinical use, and possible adverse effects of HFV. We also discuss the study results on the use of HFV in respiratory distress syndrome in preterm infants and respiratory failure in term neonates. IMPACT: Knowledge of how HFV works, how it influences cardiorespiratory physiology, and how to apply it in daily clinical practice has proven to be essential for its optimal and safe use. Therefore, we present important aspects of gas exchange, lung-protective concepts, clinical use, and possible adverse effects of HFV. The use of HFV in daily clinical practice in lung recruitment, determination of the optimal continuous distending pressure and frequency, and typical side effects of HFV are discussed. We also present study results on the use of HFV in respiratory distress syndrome in preterm infants and respiratory failure in term neonates.

Emergency button cannula vs. umbilical catheter as neonatal emergency umbilical vein access - a randomized cross-over pilot study.

OBJECTIVES: Establishing immediate intravenous access to a newborn is challenging even for trained neonatologists in an emergency situation. Correct placement of umbilical catheter or an intraosseous needle needs consistent training. We evaluated the time required to correctly place an emergency umbilical button cannula (EUC) or an umbilical catheter (UC) using the standard intersection (S-EUC or S-UC, respectively) or lateral umbilical cord incision (L-EUC) by untrained medical personnel. METHODS: Single-center cross-over pilot-study using a model with fresh umbilical cords. Video-based teaching of medical students before probands performed all three techniques after assignment to one of three cycles with different sequence, using a single umbilical cord divided in three pieces for each proband. RESULTS: Mean time required to establish L-EUC was 89.3 s, for S-EUC 82.2 s and for S-UC 115.1 s. Both application routes using the EUC were significantly faster than the UC technique. There was no significant difference between both application routes using EUC (p=0.54). CONCLUSIONS: Using an umbilical cannula is faster than an umbilical catheter, using a lateral incision of the umbilical vein is an appropriate alternative.

[Individualized Somatic Classification of Newborns Using Birth Weight Percentiles Based On Maternal Body Height and Weight (Results of a Validation Study)]. / Individuelle somatische Klassifikation von Neugeborenen auf der Grundlage von Körperhöhe und Körpergewicht der Mutter (Ergebnisse einer Validierungsstudie).

INTRODUCTION: Birth weight is influenced by maternal anthropometry. The SGA-rate of newborns of short and light mothers (<158 cm,<53 kg) and the LGA-rate of tall and heavy mothers (>177 cm,>79 kg) are overestimated. The LGA-rate of newborns of shorter mothers and the SGA-rate of taller mothers are underestimated. Individualized birth weight percentiles (IBWP) based on 18 maternal groups (6 groups of height combined with 3 groups of weight), sex and weeks of gestation have been published. The aim of this study is to validate IBWP by evaluating SGA-, AGA-, and LGA-rates using perinatal data. METHODS: The validation study compares IBWP (1995 to 2000, n=2.2 million singletons) with percentile values from two German cohorts (i: 1995 to 2000; n=2.3 million and ii: 2007 to 2011, n=3.2 million singletons) using newborns from the Lower Saxony Perinatal Survey (n=0.56 million singleton newborns, 2001 to 2009). SGA-, AGA-, and LGA-rates were calculated using R statistical analysis. RESULTS: Common percentile charts based on the total population 1995-2000 and 2007-2011 yielded SGA-rates among shorter mothers of 21.1 to 21.6% and LGA-rates of 2.0 to 3.1%. In taller mothers, SGA-rates were 3.3 to 3.5% and LGA-rates were 26.6 to 27.1%. IBWP achieved SGA-rates of 9.0% and LGA-rates of 11.4 to 11.6% in shorter mothers and SGA- and LGA-rates of 10% in taller mothers. DISCUSSION: IBWP consider the maternal size for estimation of the fetal growth potential and achieve expected SGA- and LGA-rates of 10%. Consideration of individual growth potential avoids underestimation and overestimation of SGA- and LGA-rates. It aided analyses of birth weight with IBWP simplify the assessment of the nutritional status.

[The Neonatal Subgaleal Hematoma - A Neonatal Emergency]. / Das subgaleale Hämatom beim Neugeborenen ­ ein neonatologischer Notfall.

Subgaleal hematoma (SGH) is a rare complication in neonates that may lead to hemorrhagic shock due to significant blood loss into the subgaleal space. We report of two neonates who developed subgaleal hematoma with severe hemorrhagic shock and encephalopathy. In the first case of a mature female neonate, the development of the subgaleal hematoma was promoted by early-onset sepsis and delivery by vacuum extraction. The second case, of a male preterm neonate, was a complicated fetal development followed by secondary cesarean section. Both cases highlight that a subgaleal hematoma is a severe neonatal emergency. In addition to prompt treatment of the shock, therapy of the coagulopathy is essential.

Invasive Group B Streptococcus Disease With Recurrence and in Multiples: Towards a Better Understanding of GBS Late-Onset Sepsis.

Group B Streptococcus (GBS) is a common intestinal colonizer during the neonatal period, but also may cause late-onset sepsis or meningitis in up to 0.5% of otherwise healthy colonized infants after day 3 of life. Transmission routes and risk factors of this late-onset form of invasive GBS disease (iGBS) are not fully understood. Cases of iGBS with recurrence (n=25) and those occurring in parallel in twins/triplets (n=32) from the UK and Ireland (national surveillance study 2014/15) and from Germany and Switzerland (retrospective case collection) were analyzed to unravel shared (in affected multiples) or fixed (in recurrent disease) risk factors for GBS disease. The risk of iGBS among infants from multiple births was high (17%), if one infant had already developed GBS disease. The interval of onset of iGBS between siblings was 4.5 days and in recurrent cases 12.5 days. Disturbances of the individual microbiome, including persistence of infectious foci are suggested e.g. by high usage of perinatal antibiotics in mothers of affected multiples, and by the association of an increased risk of recurrence with a short term of antibiotics [aOR 4.2 (1.3-14.2), P=0.02]. Identical GBS serotypes in both recurrent infections and concurrently infected multiples might indicate a failed microbiome integration of GBS strains that are generally regarded as commensals in healthy infants. The dynamics of recurrent GBS infections or concurrent infections in multiples suggest individual patterns of exposure and fluctuations in host immunity, causing failure of natural niche occupation.

Modes and strategies for providing conventional mechanical ventilation in neonates.

Neonatal respiratory failure is a common and serious clinical problem which in a considerable proportion of infants requires invasive mechanical ventilation. The basic goal of mechanical ventilation is to restore lung function while limiting ventilator-induced lung injury, which is considered an important risk factor in the development of bronchopulmonary dysplasia (BPD). Over the last decades, new conventional mechanical ventilation (CMV) modalities have been introduced in clinical practice, aiming to assist clinicians in providing lung protective ventilation strategies. These modalities use more sophisticated techniques to improve patient-ventilator interaction and transfer control of ventilation from the operator to the patient. Knowledge on how these new modalities work and how they interact with lung physiology is essential for optimal and safe use. In this review, we will discuss some important basic lung physiological aspects for applying CMV, the basic principles of the old and new CMV modalities, and the evidence to support their use in daily clinical practice.

Individualized sex-specific birth weight percentiles for gestational age based on maternal height and weight.

OBJECTIVES: The maternal body size affects birth weight. The impact on birth weight percentiles is unknown. The objective of the study was to develop birth weight percentiles based on maternal height and weight. METHODS: This observational study analyzed 2.2 million singletons from the German Perinatal Survey. Data were stratified into 18 maternal height and weight groups. Sex-specific birth weight percentiles were calculated from 31 to 42 weeks and compared to percentiles from the complete dataset using the GAMLSS package for R statistics. RESULTS: Birth weight percentiles not considering maternal size showed 22% incidence of small for gestational age (SGA) and 2% incidence of large for gestational age (LGA) for the subgroup of newborns from petite mothers, compared to a 4% SGA and 26% LGA newborns from big mothers. The novel percentiles based on 18 groups stratified by maternal height and weight for both sexes showed significant differences between identical original percentiles. The differences were up to almost 800 g between identical percentiles for petite and big mothers. The 97th and 50th percentile from the group of petite mothers almost overlap with the 50th and 3rd percentile from the group of big mothers. CONCLUSIONS: There is a clinically significant difference in birth weight percentiles when stratified by maternal height and weight. It could be hypothesized that birth weight charts stratified by maternal anthropometry could provide higher specificity and more individual prediction of perinatal risks. The new percentiles may be used to evaluate estimated fetal as well as birth weight.

Protocol for a prospective cohort study: Prevention of Transmissions by Effective Colonisation Tracking in Neonates (PROTECT-Neo).

INTRODUCTION: Transmissions of opportunistic bacterial pathogens between neonates increase the risk of infections with negative repercussions, including higher mortality, morbidity and permanent disabilities. The probability of transmissions between patients is contingent on a set of intrinsic (patient-related) and extrinsic (ward-related) risk factors that are not clearly quantified. It is the dual objective of the Prevention of Transmissions by Effective Colonisation Tracking-Neo study to determine the density of transmission events in a level III neonatal intensive care unit (NICU) and to identify risk factors that may be causally associated with transmission events. METHODS AND ANALYSIS: A full cohort of patients treated in a 17-bed level III NICU will be prospectively followed and transmission events between two or more patients will be documented. A transmission event occurs when isogenic isolates from two different patients can be identified. Isolates will be obtained by routine weekly screening. Isogenicity will be determined by whole-genome sequencing. During the study, relevant intrinsic and extrinsic risk factors will be recorded. Specimen and data will be collected for 1 year. We postulate that transmission density increases during episodes when demand for intensive care cannot be met by existing staff, and that threshold dynamics have a bearing on cohorting and hand hygiene performance. Poisson logistic regression, proportional hazard and multilevel competing risk models will be used to estimate the effect of explanatory variables. ETHICS AND DISSEMINATION: This study has been approved by the local ethics committee (study ID 287/18). The results will be published in peer-reviewed medical journals, communicated to participants, the general public and all relevant stakeholders. TRIAL REGISTRATION NUMBER: The German Clinical Trials Registry (DRKS00017733); Pre-results.

Surfactant replacement therapy: from biological basis to current clinical practice.

This review summarizes the current knowledge on the physiological action of endogenous and exogenous pulmonary surfactant, the role of different types of animal-derived and synthetic surfactants for RDS therapy, different modes of administration, potential risks and strategies of ventilation, and highlights the most promising aims for future development. Scientists have clarified the physicochemical properties and functions of the different components of surfactant, and part of this successful research is derived from the characterization of genetic diseases affecting surfactant composition or function. Knowledge from functional tests of surfactant action, its immunochemistry, kinetics and homeostasis are important also for improving therapy with animal-derived surfactant preparations and for the development of modified surfactants. In the past decade newly designed artificial surfactants and additives have gained much attention and have proven different advantages, but their particular role still has to be defined. For clinical practice, alternative administration techniques as well as postsurfactant ventilation modes, taking into account alterations in lung mechanics after surfactant placement, may be important in optimizing the potential of this most important drug in neonatology.

The role of tongue-tie in breastfeeding problems-A prospective observational study.

AIM: We evaluated what determined breastfeeding problems in a non-selected mother-infant cohort, with special reference to tongue-tie and improvements in breastfeeding following frenulotomy. METHODS: This 2014-2015 prospective, observational study was carried out in a tertiary level maternity unit affiliated to the University of Freiburg, Germany, using a breastfeeding questionnaire, standardised breastfeeding scores and the Assessment Tool For Lingual Frenulum Function (ATLFF). The standard intervention was breastfeeding support, a frenulotomy for tongue-tie was performed if necessary. All cases of breastfeeding problems and, or tongue-tie, were followed up by telephone 2.5 weeks after birth. RESULTS: We enrolled 776 newborn-mother dyads: 345 had breastfeeding problems, 116 had a tongue-tie and 30 underwent a frenulotomy. In the multivariate analysis, severe breastfeeding problems were more frequent in newborn infants with tongue-tie, with an odds ratio (OR) of 2.6 (P= 0.014). Other risk factors were: no breastfeeding experience (OR 4.4, P = 0.001), low birth weight (OR 2.9, P = 0.001), prematurity (OR 3.6, P = 0.000) and Caesarean section (OR 1.6, P = 0.023). There was a significant reduction in breastfeeding problems after frenulotomy (P = 0.01). CONCLUSION: Tongue-tie had a significant impact on breastfeeding and so did low birth weights and prematurity. Frenulotomy proved helpful when breastfeeding problems were reported.

[Influence of Parental Body Measurements on Birth Weight of Eutrophic Term Newborns with Special Consideration of Paternal Body Measurements]. / Zum Einfluss von Körpermaßen der Eltern auf das Geburtsgewicht von eutrophen Termingeborenen (TG) unter besonderer Berücksichtigung der Körperhöhe und des Körpergewichts des Vaters.

A significant influence of maternal body height and weight on neonatal birth outcome has been confirmed before, whereas the influence of paternal traits is rather unknown. In order to analyze the correlation between parental body measurements and the birth weight of newborns, data of 1312 eutrophic term newborns and their parents were collected based on a multicenter study in 10 participating German maternity clinics. The collected data included the birth weight of the infants and the body height and weight of their parents. The results show a significant correlation between infant birth weight and maternal body height. Even with a constant body height and body weight of fathers in a range between 176-184 cm and 76-84 kg, taller mothers gave birth to children with a higher birth weight than shorter mothers. Furthermore, higher maternal body weight is also correlated with increased birth weights, although this correlation is attenuated in higher maternal weight groups. Data regarding body weight and body height of fathers showed similar results with regard to birth weight of the newborns. At a constant maternal body height (164-172 cm) and weight (56-64 kg), the body weight of newborns significantly correlates with the body height of fathers but not with their body weight. The multivariable regression analysis resulted in the following ranking of influence factors on the birth weight of newborns: 1) body height of mother, 2) body weight of mother, 3) body height of father. The results gave support to the assumption of a certain genetic influence of parental body stature on their neonates but argue for an even stronger impact of maternal environmental conditions on the developmental status of neonates.

Risk-adjusted mortality of VLBW infants in high-volume versus low-volume NICUs.

OBJECTIVE: To examine whether the number of very low birthweight (VLBW) infants treated annually in neonatal intensive care units (NICUs) (hospital volume) has an effect on their in-hospital mortality under the regulatory conditions in Germany. SETTING: The study included VLBW infants with <33 weeks of gestational age and birth weight below 1500 g admitted to NICUs in the state of Baden-Wüerttemberg, Germany, from 2003 to 2008. Cases were extracted from the compulsory German neonatal quality assurance programme with variables essential for calculation of the Clinical Risk Index for Babies (CRIB) and PREM birth model (PREM(bm)) scores. The cohort was divided into four subgroups corresponding to their disease severity (low, intermediate, high and very high) according to each score. Low-volume NICUs (LV-NICUs) were defined as treating up to 50 cases per year, while high-volume NICUs >50 cases. RESULTS: After exclusion of infants with lethal malformations, 5340 cases from 32 units were analysed. While raw mortality was comparable, infants in LV-NICUs had an increased mortality after risk adjustment with the CRIB and PREM(bm) scores (OR 1.48 (95% CI 1.16 to 1.90), p=0.002 with CRIB; and OR 1.39 (95% CI 1.11 to 1.76), p=0.005 with PREM(bm)). In a subgroup analysis mortality was significantly higher for LV-NICUs in the intermediate disease severity group (OR 1.49 (95% CI 1.02 to 2.17), p=0.037 with CRIB) and in the high-risk group (OR 1.70 (95% CI 1.16 to 1.90), p=0.002 with CRIB; and OR 1.39 (95% CI 1.11 to 1.76), p=0.005 with PREM(bm)), but not in the low-risk and very high-risk subgroups. CONCLUSION: Depending on the severity of the disease, the risk-adjusted mortality in German NICUs with 50 or less annual cases of VLBW infants may be significantly increased.

Maternal body mass index and smoking during pregnancy do not affect the proportional sexual dimorphism for birth weight- an analysis of the German Perinatal Survey.

Background: Male sex has been reported as a risk factor for perinatal mortality. It can be hypothesized that smoking during pregnancy and low maternal pre-pregnancy body mass index (BMI) would lead to a higher proportion of growth restricted male compared to female newborns. The objective of the study was to analyze sex-specific differences in birth weight related to smoking and maternal BMI. Method: Data on maternal and newborn characteristics were obtained from the German Perinatal Survey. We analyzed data on 508,926 singleton pregnancies that had been collected in eight German federal states between 1998 and 2000. Women were classified according to the number of cigarettes smoked per day (non-smokers, 1-7, 8-14, ≥ 15) and by maternal BMI (< 18.5, 18.5-24.99, 25-29.99, ≥ 30 kg/m2) at the first obstetric consultation. Newborns were classified as small, appropriate, or large for gestational age based on birth weight below the 10th, between 10th and 90th, or above the 90th percentile, respectively. The proportional sexual dimorphism (PSD) was calculated as the female mean divided by the male mean ×100. Results: Smoking is related to a decrease in mean birth weight and an increase of in the SGA rate. Maternal BMI is positively related to the birth weight. However, the proportional sexual dimorphism for birth weight was not different with smoking or BMI. Conclusion: Smoking during pregnancy is related to lower birth weight, and high BMI is related to higher birth weight with no change in PSD.

High-Temperature Short-Time Treatment of Human Milk for Bacterial Count Reduction.

Background: Human milk (HM) for preterm infants will often be pasteurized for cytomegalovirus (CMV) inactivation and reduction of its bacterial count. High-temperature short-time (HTST) treatment compared to standard Holder pasteurization (HoP) reduces the impact of heat treatment on bioactive HM proteins while effectively inactivating CMV. No data are available for the efficacy of bacterial count reduction using HTST treatments that are available for clinical use. Objective: To test the antiviral and antibacterial efficacy of HTST treatment protocols in HM using a modified HTST treatment device compared to standard HoP. Methods: Holder pasteurized 95 mL HM samples were inoculated with Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), Serratia marcescens (Smarc 00697), two different strains of Klebsiella pneumoniae (ATCC 700603 and Kpn 01605) or spiked with 2 × 105 50% tissue culture infective dose of CMV (AD169) and subsequently subjected to HoP (62.5°C/30 min) or HTST treatment (62°C/5 s, 62°C/15 s, 72°C/5 s, 72°C/15 s, 87°C/2 s, and 87°C/5 s). Bacterial count was determined after treated HM was cultured for 24 h. CMV infectivity was determined by the number of specific CMV immediate early antigen stained nuclei after inoculating human fibroblasts with appropriately prepared HM samples. Results: Holder pasteurized samples revealed no growth after 24 h incubation. Viable bacterial cultures were retrieved from all tested strains after HTST treatment with the default HTST protocol (62°C/5 s) that is available for clinical use. Using other time-temperature combinations, growth rates of S. aureus, E. faecalis, P. aeruginosa, K. pneumoniae, K. pneumonia, and S. marcescens were depending on treatment time, treatment temperature, bacterial genera and strain. Only after treatment temperatures above 72°C no bacterial growth was observed. CMV was inactivated by any tested time-temperature combination. Conclusions: HTST treatment inactivates CMV in 95 mL HM samples but is less effective than HoP in bacterial count reduction at a time-temperature combination of 62°C/5 s. For a reliable bacterial count reduction HTST treatment at 87°C was required in this study.

Somatic development at birth as influenced by maternal characteristics - an analysis of the German Perinatal Survey.

We investigated the effects of maternal age, body weight, body height, weight gain during pregnancy, smoking during pregnancy, previous live births and being a single mother on somatic development at birth. We analysed data from the German Perinatal Survey for the years 1998-2000 from eight German federal states. We had available data on 508,926 singleton pregnancies and neonates in total; for 508,893 of which we could classify the neonates as small, appropriate or large for gestational age (SGA, AGA or LGA) based on the 10th and 90th birth weight percentiles. Multivariable regression analyses found statistically significant effects of a clinically relevant magnitude for smoking during pregnancy [odds ratio (OR) 2.9 for SGA births for women smoking >10 cigarettes per day], maternal height (OR 1.4 for SGA births for women <162 cm; OR 1.4 for LGA births for women >172 cm), maternal weight (OR 1.5 for SGA births for women <59 kg; OR 1.9 for LGA births for women >69 kg), weight gain during pregnancy (OR 1.9 for SGA births for women with a weight gain <8 kg; OR 2.0 for LGA births for women with a weight gain >18 kg) and previous live births (OR 2.1 for LGA births for women with one or more previous live births). Maternal age and being a single mother also had significant effects but their magnitude was small. Our analysis confirms the clinically relevant effects of smoking, maternal anthropometric measures and weight gain during pregnancy on neonatal somatic development.

Breastfeeding problems should be the only relevant criteria for deciding whether to carry out a frenotomy in infancy.

Performing a frenotomy on tongue-tied infants is controversial, particularly with regard to breastfeeding issues. This paper reviews the literature to bring together clinical experiences and scientific evidence in this field. I found that some tongue-tied babies may exhibit breastfeeding problems, while others may feed perfectly. The literature suggests that medical breastfeeding-related problems should be the only relevant criteria to guide the decision-making for a frenotomy in infancy. The advantages and disadvantages of either a wait and see position or surgical approach are addressed. CONCLUSION: The cornerstones for best practice are the meticulous examination, correct diagnosis and classification of tongue-tied infants.

Maternal body height is a stronger predictor of birth weight than ethnicity: analysis of birth weight percentile charts.

Background Anthropometric parameters such as birth weight (BW) and adult body height vary between ethnic groups. Ethnic-specific percentile charts are currently being used for the assessment of newborns. However, due to globalization and interethnic families, it is unclear which charts should be used. A correlation between a mother's height and her child's BW (1 cm accounts for a 17 g increase in BW) has been observed. The study aims to test differences in small for gestational age (SGA) and large for gestational age (LGA) rates, employing BW percentile charts based on maternal height between ethnic groups. Methods This retrospective study of 2.3 million mother/newborn pairs analyzed BW, gestational age, sex, maternal height and ethnicity from the German perinatal survey (1995-2000). These data were stratified for maternal height (≤157, 158-163, 164-169, 170-175, ≥176 cm) and region of origin (Germany, Central and Northern Europe, North America, Mediterranean region, Eastern Europe, Middle East and North Africa, and Asia excluding Middle East). Percentile charts were calculated for each maternal height group. Results The average BW and maternal height differ significantly between ethnic groups. On current percentile charts, newborns of taller mothers (≥176 cm) have a low rate of SGA and a high rate of LGA, whereas newborns of shorter mothers (≤157 cm) have a high rate of SGA and a low rate of LGA. When the BW data are stratified based on the maternal height, mothers of similar height from different ethnic groups show similar average BWs, SGA and LGA rates. Conclusion Maternal body height has a greater influence on BW than maternal ethnicity. The use of BW percentile charts for maternal height should be considered.