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.

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.

[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.

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.

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.

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.

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.

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.

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.

High-temperature short-time pasteurisation of human breastmilk is efficient in retaining protein and reducing the bacterial count.

AIM: Milk banks are advised to use Holder pasteurisation to inactivate the cytomegalovirus, but the process adversely affects the bioactive properties of human breastmilk. This study explored the antibacterial efficacy of an alternative high-temperature short-time (HTST) treatment of human breastmilk and its effect on marker proteins, compared with the Holder method. METHODS: Breastmilk samples were obtained from 27 mothers with infants in a German neonatal intensive care unit. The samples were either heated to 62°C for five seconds using HTST or processed using Holder pasteurisation, at 63 ± 0.5°C for 30 minutes. Immunoglobulin A, lactoferrin, lysozyme, alkaline phosphatase and bile salt-stimulated lipase concentrations and bacterial colony-forming units/mL were measured before and after heating. RESULTS: HTST-treated samples retained higher rates of immunoglobulin A (95% versus 83%), alkaline phosphatase (6% versus 0%) and bile salt-stimulated lipase (0.8% versus 0.4%) than Holder pasteurisation samples (all p < 0.01), but not lactoferrin (32% versus 20%, p = 0.18) and lysozyme (72% versus 65%, p = 1). No difference in antibacterial efficacy was noted between the two groups (p = 0.29). CONCLUSION: Using the HTST treatment protocol retained some of the bioactive properties of human breastmilk and appeared to have similar antibacterial efficacy to Holder pasteurisation.

Carboxyhemoglobin - the forgotten parameter of neonatal hyperbilirubinemia.

BACKGROUND: Neonatal hyperbilirubinemia is influenced by a wide variety of factors, one of which is hemolysis. Serious hyperbilirubinemia may lead to a kernicterus with detrimental neurologic sequelae. Patients suffering from hemolytic disease have a higher risk of developing kernicterus. Carbon monoxide (CO), a byproduct of hemolysis or heme degradation, was described by Sjöstrand in the 1960s. It is transported as carboxyhemoglobin (COHb) and exhaled through the lungs. We were interested in a potential correlation between COHb and total serum bilirubin (TSB) and the time course of both parameters. MATERIALS AND METHODS: We used a point of care (POC) blood gas analyzer and did a retrospective analysis of bilirubin and COHb data collected over a 60-day period. RESULTS: An arbitrary cut-off point set at 2% COHb identified four patients with hemolytic disease of different origins who required phototherapy. In one patient with atypical hemolytic uremic syndrome (aHUS), COHb preceded the rise in bilirubin by about 2 days. Despite this displacement, there was a moderately good correlation of COHb with TSB levels <15 mg/dL (257 µmol/L) (r2: 0.80) and direct bilirubin (r2: 0.78) in the first patient. For all the four patients and all time points the correlation was slightly lower (r2: 0.59). CONCLUSIONS: COHb might be useful as a marker for high hemoglobin turnover to allow an earlier identification of newborns at risk to a rapid rise in bilirubin.

[Antenatal Steroid Therapy in Threatened Premature Birth - State of the Art]. / Sinnvolle Steroidprophylaxe bei drohender Frühgeburt ­ State of the art.

The aim of this work is to provide an overview of the recommendations in the current literature for the induction of lung maturation therapy. In particular, special attention is focused on specific situations, such as chorioamnionitis, intrauterine growth retardation and preeclampsia, which often lead to premature birth. Additionally, some aspects of antenatal steroid therapy, despite its widespread use, still require clarification. Among them is the repetitive administration of steroid therapy. On the basis of the Cochrane analysis of 2015, advantages and disadvantages for children and pregnant women are explained. Furthermore, the data on the use of antenatal steroid therapy in multiple pregnancies remain insufficient.

Cytokines in noninvasively obtained amniotic fluid as predictors of fetal inflammatory response syndrome.

BACKGROUND: In patients with preterm premature rupture of membranes, intrauterine inflammation and/or infection is frequently present, can lead to fetal inflammatory response syndrome, and is associated with adverse neonatal outcome. Clinical decision making requires balancing the potential benefits of pregnancy prolongation against the risk of intrauterine infection. Diagnostic tests in maternal serum are of moderate prediction value and amniocentesis is an invasive procedure. Therefore, markers obtained noninvasively would be helpful in patients with expectant management. OBJECTIVES: To determine the predictive values of amniotic fluid interleukin-6 and tumor necrosis factor-α in vaginal secretions for fetal inflammatory response syndrome and/or histologic funisitis and for adverse neonatal outcome in patients with preterm premature rupture of membranes. STUDY DESIGN: In this prospective multicenter case-control study, vaginal secretions were sampled daily with a noninvasive method from 99 women with preterm premature rupture of membranes and expectant management. Amniotic fluid interleukin-6 and tumor necrosis factor-α were measured by 2 different immunoassays (an automated chemiluminescent enzyme immunoassay and a lateral flow immunoassay). After delivery, patients were divided into a control or a fetal inflammatory response syndrome group according to neonatal interleukin-6 in cord plasma and/or the presence of funisitis. Univariate and multivariate regression analyses were performed and prediction models were developed by calculating receiver operating characteristic curves. RESULTS: Gestational age at delivery was lower and latency period was longer in the fetal inflammatory response syndrome group compared to the control group. The strongest risk factor for composite adverse neonatal outcome was fetal inflammatory response syndrome (odds ratio, 2.48; confidence interval, 1.40-4.38). The median concentrations of amniotic fluid interleukin-6 and tumor necrosis factor-α in vaginal secretions were significantly higher in the fetal inflammatory response group compared to the control group in both immunoassays (P < .001). The area under the curve of the clinical reference model (including common clinical parameters) was 0.66. Adding interleukin-6 and tumor necrosis factor-α into the model improved the area under the curve to 0.92 (in both assays, interleukin-6 IMMULITE and QuickLine); 0.87 (tumor necrosis factor-α IMMULITE) and 0.94 (tumor necrosis factor-α QuickLine), respectively. CONCLUSION: The strongest risk factor for worse neonatal outcome (composite neonatal outcome) was fetal inflammatory response syndrome. Amniotic fluid interleukin-6 and tumor necrosis factor-α seem to be good predictors for fetal inflammatory response syndrome and for histologic funisitis and may improve the clinical management of patients with preterm premature rupture of membranes. The noninvasive technique of sampling amniotic fluid from vaginal secretions facilitates daily measurements and bedside assessment of cytokines and is in this respect preferable to invasive amniocentesis.

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.

Lethal course of meconium ileus in preterm twins revealing a novel cystic fibrosis mutation (p.Cys524Tyr).

BACKGROUND: In term newborns meconium ileus is frequently associated with cystic fibrosis. Reports on meconium ileus in preterm infants being diagnosed with cystic fibrosis early after birth are very scarce. Associations between genotype and phenotype in cystic fibrosis and its particular comorbidities have been reported. CASE PRESENTATION: Two extremely preterm twin infants (26 weeks of gestation) born from a Malaysian mother and a Caucasian father were presented with typical signs of meconium ileus. Despite immediate surgery both displayed a unique and finally lethal course. Mutation analysis revealed a novel, probably pathogenic cystic fibrosis mutation, p.Cys524Tyr. The novel mutation might explain the severity of disease next to typical sequelae of prematurity. CONCLUSION: Preterm neonates with meconium ileus have to be evaluated for cystic fibrosis beyond ethnical boundaries, but may take devastating clinical courses despite early treatment. The novel, potentially pathogenic CF mutation p.Cys524Tyr might be associated with severe meconium ileus in neonates. Disease-modifying loci are important targets for intestinal comorbidity of cystic fibrosis.