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Purpose: Craniofacial disorders (CD) affect the Oral Health Impact Profile (OHIP). Therefore, this study evaluates the OHIP in orthodontic patients with cleft lip and/or palate or Robin sequence compared to healthy controls (C)., Methods: A prospective, cross-sectional study was conducted. Oral health-related quality of life (OHRQoL) was assessed using the OHIP-14 questionnaire, with responses categorized into functional and psychological well-being items. In addition, the study considered the influence of crossbite, orthodontic appliance type, oral hygiene, and speech therapy. A high OHIP score represents a good quality of life. The Mann-Whitney test was used for nonparametric quantitative variables; statistical significance was set at p < 0.05., Results: The study included 119 participants (ages 7-21 years; 61 male, 58 female), divided into a CD group consisting of patients with cleft lip and/or palate or Robin sequence (n = 42) and a control group (C; n = 77; mean age 13.5 ± 5.2 and 14.3 ± 3.3 years, respectively). Both groups showed comparable OHIP-14 scores. The CD group reported significantly higher satisfaction regarding nutritional intake (p = 0.03), while the social and psychological dimensions were reduced (p = 0.04). Factors like crossbite, orthodontic appliance and speech therapy did not have a significant impact on OHIP. CD patients with good oral hygiene showed significantly superior self-reported psychological OHIP (p = 0.04)., Conclusion: Patients with cleft lip and/or palate or with Robin sequence exhibited OHIP scores comparable to healthy individuals despite their underlying condition. Early guidance on dental care and tooth-friendly nutrition has the potential to improve OHRQoL. Additionally, providing supplemental psychological support during orthodontic treatment is advisable., Competing Interests: Declarations. Conflict of interest: C. Weismann, M. Schmidt, J. Effert, M.C. Schulz, C.F. Poets, B. Koos and M. Aretxabaleta declare that they have no competing interests. Ethical standards: This study was reviewed and approved by the institutional ethics committee of Tübingen University Hospital, with the approval number: 188/2019BO1. All participants or their legal guardians provided informed consent to participate in the study. Written informed consent was obtained from all legal guardians., (© 2025. The Author(s).)

Background: Mandibular distraction osteogenesis (MDO) and pre-epiglottic baton plates (PEBP) are both effective for early management of upper airway obstruction (UAO) in infants with Robin sequence (RS), but have not been directly compared. The purpose of this study was to compare early airway, feeding and growth outcomes between these treatments., Methods: This is a bicentric retrospective cohort study from 2015-2021 including infants with RS treated with MDO or PEBP before 6 months-of-age with pre- and post-treatment sleep studies and follow-up at least through age 1-year. The primary outcome was immediate post-intervention UAO, measured as obstructive apnea-hypopnea index (oAHI) or obstructive apnea index (oAI), as available. Latest follow-up sleep studies, feeding and growth characteristics were also assessed., Results: 114 subjects were included: MDO, n=31 and PEBP, n=83. Pre-treatment UAO was similar between groups (p=0.61). PEBP was initiated at a younger age (median [IQR] 31 [14,53] vs. 41 [28,84] days-of-life, p<0.05). Significant reduction of oAHI/oAI was achieved in both groups, but greater with MDO (98%) compared to PEBP (94%, p<0.05). PEBP demonstrated better early feeding and growth outcomes compared to MDO, with fewer surgical feeding tubes (p<0.001) and more rapid early growth (p=0.038). When stratified by pre-intervention UAO, infants starting with moderate UAO experienced similar airway outcomes with both treatments (p=0.11), while those with severe UAO had greater resolution with MDO (p<0.001)., Conclusion: Both treatments effectively relieve moderate UAO in infants with RS, but MDO is more effective for infants with severe respiratory compromise., Competing Interests: Jens de Gijsel: No conflicts of interest. Snigdha Jindal: No conflicts of interest. Mirja Quante: No conflicts of interest. Christian Poets: No conflicts of interest. Eliot Katz: No conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.)

Introduction: The aim of this study was to investigate the orthodontic treatment needs (OTN) of children with RS treated with the TPP in infancy compared to age- and sex-matched controls., Methods: The aim of this study was to investigate the orthodontic treatment needs (OTN) of children with RS treated with the TPP in infancy compared to age- and sex-matched controls., Results: In 21 children with RS (n = 23; 19 non-syndromic, 4 syndromic; average age 9.9 years) showed high OTN, which was significantly higher than in controls (n = 21). The latter of 9 controls had minor OTN, followed by 8 participants with borderline OTN. Regarding the intraoral picture, patients with RS had an increased open bite tendency. Without considering the presence of a cleft palate, 16 children with RS had high or very high OTN, compared to 4 of controls., Conclusions: Patients with RS have significantly higher OTN than healthy controls, independent of cleft occurrence. RS is associated with dental anomalies and special skeletal growth patterns, both increasing malocclusion and negatively affecting dentoalveolar growth. This should raise awareness for identifying these needs and provide a comprehensive orthodontic treatment, where functional rehabilitation should be favored over aesthetic results., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine whether the prefrontal space ratio (PSFR), inferior facial (IFA) and maxilla-nasion-mandible angle (MNM), and the fetal profile line (FPL) are helpful in identifying fetuses with Robin sequence (RS) in cases with isolated retrognathia, and thus better predict the likelihood of immediate need for postnatal respiratory support., Methods: This was a retrospective matched case-control study of fetuses/infants with isolated retrognathia with or without RS receiving pre- and postnatal treatment at the University Hospital of Tübingen, Germany between 2008 and 2020. The PFSR, IFA, MNM, and FPL were measured in affected and normal fetuses according to standardized protocols. Cases were stratified into isolated retrognathia and RS., Results: 21 (n=7 isolated retrognathia, n=14 RS) affected fetuses and 252 normal fetuses were included. Their median gestational age at ultrasound examination was 23.6 and 24.1 weeks, respectively. In fetuses with isolated retrognathia and RS, the PSFR, IFA, and FPL were significantly different from the normal population. At a false-positive rate of 5%, the detection rate was 76.2% for the PFSR, 85.7% for the IFA, and 90.5% for both parameters combined. However, all parameters failed to distinguish between isolated retrognathia and RS., Conclusion: PSFR and IFA are simple markers for identifying retrognathia prenatally. However, they are not helpful for the detection of RS in fetuses with isolated retrognathia. Therefore, delivery should take place in a center experienced with RS and potentially life-threatening airway obstruction immediately after birth., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Inhaled bronchodilators improve pulmonary function. Their effects on bronchopulmonary dysplasia (BPD) are uncertain. We assessed the efficacy of early inhaled bronchodilators on the risk of BPD and death in extremely preterm infants. Methods: We performed a post-hoc analysis of prospectively collected data from the Neonatal European Study of Inhaled Steroids (NEuroSIS). In NEuroSIS, 863 extremely preterm infants were randomly assigned to receive early inhaled budesonide or placebo. We now performed nonrandomized comparisons between infants that participated in the NEUROSIS trial and either received early (within the first 48 h of life) bronchodilators or no bronchodilators. Groups were assembled according to predefined criteria stated in the study protocol and we used the same prespecified primary outcome as in the main study, a composite of BPD and death at a postmenstrual age of 36 weeks. Results: Treatment groups did not differ significantly in the composite outcome of BPD and death at 36 weeks postmenstrual age: bronchodilator group (20/46; 43.5%), versus 349/810 (43.1%) in the no bronchodilator group; ( p = .97). Analyzed by individual components, there were no significant differences in BPD and death rates between the groups. Discussion: Based on our analyses, early inhaled bronchodilators did not reduce the risk of BPD and death in extremely preterm infants.

Background: Orthodontic treatment of newborns and infants with Robin-Sequence using the Tübingen Palatal Plate (TPP) is a complex procedure that could benefit from simplification through digitalization. The design of the velar extension (spur) and the palatal base determines the success of the treatment. Therefore, a prototype must be produced and inserted under endoscopic supervision in order to determine the appropriate shape, length and position of the spur. This technical note demonstrates a fully digital workflow for the design and manufacturing of a functional TPP prototype, based on an intraoral scan. This prototype can be altered and individualized digitally for each patient. After the shape and position of the spur have been optimized, the prototype is duplicated using a silicone mold. Then the definitive TPP is manufactured and inserted. We aim to present a workflow which facilitates the fitting procedure and does not require a conventional impression or a physical model to create the appliance., Methods: As described in part I of this series, the intraoral scan is performed using the 3Shape TRIOS3 scanner and its corresponding acquisition software. The virtual model is rendered in the 3Shape ortho appliance designer and the base of the palatal plate is designed in the 3Shape dental designer. The palatal plate and the virtual model are then imported into Autodesk Meshmixer and a standardized spur is positioned and merged with the base. The TPP is exported in Standard Tessellation Language (STL) format and manufactured on a W2P Solflex 170 DLP printer using VOCO VPrint Splint material (MDR Class IIa)., Results: Based on an intraoral scan, the TPP prototype could be successfully manufactured and proved suitable for the patients' treatment., Conclusion: The new digital workflow for the design of the TPP can been successfully implemented into daily clinical routine in our facility. Patients could be alleviated from having to undergo conventional impression procedures and fitting of the TPP could be facilitated by producing multiple functional prototypes for endoscopic evaluation. Through rapid prototyping, the expenditure of the fitting process was reduced, which makes the TPP therapy more efficient and accessible to a wider range of clinicians.

Background: Advanced digital workflows in orthodontics and dentistry often require a combination of different software solutions to create patient appliances, which may be a complex and time-consuming process. The main objective of this technical note is to discuss treatment of craniofacial anomalies using digital technologies. We present a fully digital, linear workflow for manufacturing palatal plates for infants with craniofacial anomalies based on intraoral scanning. Switching to intraoral scanning in infant care is advantageous as taking conventional impressions carries the risk of impression material aspiration and/or infections caused by material remaining in the oronasal cavity., Material and Methods: The fully digital linear workflow presented in this technical note can be used to design and manufacture palatal plates for cleft palate patients as well as infants with functional disorders. We describe the workflow implemented in an infant with trisomy 21. The maxilla was registered using a digital scanner and a stimulation plate was created using dental CAD software and an individual impression tray module on a virtual model. Plates were manufactured using both additive and subtractive methods. Methacrylate based light curing resin and Poly-Ether-Ether-Ketone were the materials used., Results: The palatal area was successfully scanned to create a virtual model. The plates fitted well onto the palatal area. Manual post-processing was necessary to optimize a functional ridge along the vestibular fold and remove support structures from the additively manufactured plate as well as the milled plate produced from a blank. The additively manufactured plate fitted better than the milled one., Conclusion: Implementing a fully digital linear workflow into clinical routine for treatment of neonates and infants with craniofacial disorders is feasible. The software solution presented here is suitable for this purpose and does not require additional software for the design. This is the key advantage of this workflow, which makes digital treatment accessible to all clinicians who want to deal with digital technology. Whether additive or subtractive manufacturing is preferred depends on the appliance material of choice and influences the fit of the appliance.

Importance: There are potential benefits and harms of hyperoxemia and hypoxemia for extremely preterm infants receiving more vs less supplemental oxygen., Objective: To compare the effects of different target ranges for oxygen saturation as measured by pulse oximetry (Spo2) on death or major morbidity., Design, Setting, and Participants: Prospectively planned meta-analysis of individual participant data from 5 randomized clinical trials (conducted from 2005-2014) enrolling infants born before 28 weeks' gestation., Exposures: Spo2 target range that was lower (85%-89%) vs higher (91%-95%)., Main Outcomes and Measures: The primary outcome was a composite of death or major disability (bilateral blindness, deafness, cerebral palsy diagnosed as ≥2 level on the Gross Motor Function Classification System, or Bayley-III cognitive or language score <85) at a corrected age of 18 to 24 months. There were 16 secondary outcomes including the components of the primary outcome and other major morbidities., Results: A total of 4965 infants were randomized (2480 to the lower Spo2 target range and 2485 to the higher Spo2 range) and had a median gestational age of 26 weeks (interquartile range, 25-27 weeks) and a mean birth weight of 832 g (SD, 190 g). The primary outcome occurred in 1191 of 2228 infants (53.5%) in the lower Spo2 target group and 1150 of 2229 infants (51.6%) in the higher Spo2 target group (risk difference, 1.7% [95% CI, -1.3% to 4.6%]; relative risk [RR], 1.04 [95% CI, 0.98 to 1.09], P = .21). Of the 16 secondary outcomes, 11 were null, 2 significantly favored the lower Spo2 target group, and 3 significantly favored the higher Spo2 target group. Death occurred in 484 of 2433 infants (19.9%) in the lower Spo2 target group and 418 of 2440 infants (17.1%) in the higher Spo2 target group (risk difference, 2.8% [95% CI, 0.6% to 5.0%]; RR, 1.17 [95% CI, 1.04 to 1.31], P = .01). Treatment for retinopathy of prematurity was administered to 220 of 2020 infants (10.9%) in the lower Spo2 target group and 308 of 2065 infants (14.9%) in the higher Spo2 target group (risk difference, -4.0% [95% CI, -6.1% to -2.0%]; RR, 0.74 [95% CI, 0.63 to 0.86], P < .001). Severe necrotizing enterocolitis occurred in 227 of 2464 infants (9.2%) in the lower Spo2 target group and 170 of 2465 infants (6.9%) in the higher Spo2 target group (risk difference, 2.3% [95% CI, 0.8% to 3.8%]; RR, 1.33 [95% CI, 1.10 to 1.61], P = .003)., Conclusions and Relevance: In this prospectively planned meta-analysis of individual participant data from extremely preterm infants, there was no significant difference between a lower Spo2 target range compared with a higher Spo2 target range on the primary composite outcome of death or major disability at a corrected age of 18 to 24 months. The lower Spo2 target range was associated with a higher risk of death and necrotizing enterocolitis, but a lower risk of retinopathy of prematurity treatment.

Objective: Acoustic analyses of snoring sounds have been used to objectively assess snoring and applied in various clinical problems for adult patients. Such studies require highly automatized tools to analyze the sound recordings of the whole night's sleep, in order to extract clinically relevant snore- related statistics. The existing techniques and software used for adults are not efficiently applicable to snoring sounds in children, basically because of different acoustic signal properties. In this paper, we present a broad range of acoustic characteristics of snoring sounds in children (N  =  38) in comparison to adult (N  =  30) patients., Approach: Acoustic characteristics of the signals were calculated, including frequency domain representations, spectrogram-based characteristics, spectral envelope analysis, formant structures and loudness of the snoring sounds., Main Results: We observed significant differences in spectral features, formant structures and loudness of the snoring signals of children compared to adults that may arise from the diversity of the upper airway anatomy as the principal determinant of the snore sound generation mechanism. Furthermore, based on the specific audio features of snoring children, we proposed a novel algorithm for the automatic detection of snoring sounds from ambient acoustic data specifically in a pediatric population. The respiratory sounds were recorded using a pair of microphones and a multi-channel data acquisition system simultaneously with full-night polysomnography during sleep. Brief sound chunks of 0.5 s were classified as either belonging to a snoring event or not with a multi-layer perceptron, which was trained in a supervised fashion using stochastic gradient descent on a large hand-labeled dataset using frequency domain features., Significance: The method proposed here has been used to extract snore-related statistics that can be calculated from the detected snore episodes for the whole night's sleep, including number of snore episodes (total snoring time), ratio of snore to whole sleep time, variation of snoring rate, regularity of snoring episodes in time and amplitude and snore loudness. These statistics will ultimately serve as a clinical tool providing information for the objective evaluation of snoring for several clinical applications.

Background: Recent studies indicate an increasing use of less invasive surfactant administration. Different techniques have been shown with distinct risks and benefits. The aim of this study was to develop a new method that simplifies this procedure., Objectives: An applicator was developed and tested on a manikin to make tracheal surfactant application easier and faster., Methods: A device for oral administration of a catheter into the trachea was developed. After refining, it was tested by 9 neonatologists on a manikin. The primary aim was device feasibility, which was defined as successful intubation within 30 s., Results: The first device showed success in 30 of 33 measurements (90.9%). After refinement, the final device showed successful intubation in all 27 trials (100%)., Conclusion: The new technique was feasible in this manikin test and should be confirmed in a clinical study., (© 2016 S. Karger AG, Basel.)

Background: In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025., Methods: We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts., Results: Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour., Conclusion: These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed.

Stabilization of respiration and oxygenation continues to be one of the main challenges in clinical care of the neonate. Despite aggressive respiratory support including mechanical ventilation, continuous positive airway pressure, oxygen and caffeine therapy to reduce apnea and accompanying intermittent hypoxemia, the incidence of intermittent hypoxemia events continues to increase during the first few months of life. Even with improvements in clinical care, standards for oxygen saturation targeting and modes of respiratory support have yet to be identified in this vulnerable infant cohort. In addition, we are only beginning to explore the association between the incidence and pattern of cardiorespiratory events during early postnatal life and both short- and long-term morbidity including retinopathy of prematurity, growth, sleep-disordered breathing and neurodevelopmental impairment. Part 1 of this review included a summary of lung development and diagnostic methods of cardiorespiratory monitoring. In Part 2 we focus on clinical interventions and the short- and long-term consequences of cardiorespiratory events in preterm infants.

Every year, an estimated 15 million infants are born prematurely (<37 weeks gestation) with premature birth rates ranging from 5 to 18% across 184 countries. Although there are a multitude of reasons for this high rate of preterm birth, once birth occurs, a major challenge of infant care includes the stabilization of respiration and oxygenation. Clinical care of this vulnerable infant population continues to improve, yet there are major areas that have yet to be resolved including the identification of optimal respiratory support modalities and oxygen saturation targets, and reduction of associated short- and long-term morbidities. As intermittent hypoxemia is a consequence of immature respiratory control and resultant apnea superimposed upon an immature lung, improvements in clinical care must include a thorough knowledge of premature lung development and pathophysiology that is unique to premature birth. In Part 1 of a two-part review, we summarize early lung development and diagnostic methods for cardiorespiratory monitoring.

Background: Weight gain before the clinical diagnosis of necrotising enterocolitis (NEC) is described as a predictive factor., Hypothesis: Weight gain of more than 5% one day prior to clinical suspicion plus increase of plasma Iinterleukin-8 (IL-8) are predictive for NEC., Methods: 48 infants with diagnosis of NEC stage II and III were enrolled in a case-control study. Oral and parenteral nutrition, diuresis and kinetics of weight and of IL-8 were documented., Results: 31 infants with NEC-II and 17 infants with NEC-III were enrolled. Weight gain>5% occurred in 35.3% of NEC-III, in 0% of NEC-II and in 4.2% of the control group. IL-8 increased significantly [NEC-III (6 561.4 pg/mL) vs. NEC-II: (326.7 pg/mL) vs. control group (38.9 pg/mL); p<0.05]. Sensitivity of IL-8 in NEC-II was 87.10% (70.15-96.25) and in NEC-III 100.00% (80.33-100.00). Sensitivity of weight gain was 0.00% (0.00-11.32) in NEC-II and 35.29% (14.30-61.65) in NEC-III., Conclusion: Weight gain>5% was found in only 35.3% of the cases with NEC-III. Combination of weight gain and IL-8 did not improve the diagnosis of NEC., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Irregular breathing causing hypoxia and bradycardia is a common problem of preterm infants but its pathophysiology is incompletely understood. Agitation provoked by environmental noise may play a role. We wanted to know if earmuffs can at least halve the rate of intermittent hypoxia in premies., Patients and Methods: In this randomized controlled trial 31 infants (14 male; median [min.-max.] birth weight and gestational age: 1 323 g [560-1 990] and 30(1/7) weeks [25(5/7)-33(0/7)]) had the effect of earmuffs on the frequency of pulse oximeter desaturations (SpO(2) <80%) and bradycardia events (<80 beats per minute) tested, documented via a standard home monitor. Infants were measured 2 h each with or without earmuffs; the sequence of intervention was randomised. Measurement conditions were kept constant while a noise meter recorded sound pressure levels at a 1 Hz sampling rate., Results: Median sound pressure level was 46.8 dB(A). In a pre-study, ear muffs yielded a sound reduction by 7.2 dB. 19 infants had a total of 474 desaturations. The median (25.-75. percentile) number of desaturations was 1 (1-10.5) without, and 1 (1-10) with earmuffs. The amount of infants with at least one desaturation was equal in both treatment protocols. Only 7 bradycardias occurred., Conclusion: The earmuffs had, in a rather quiet environment, no effect on intermittent hypoxia in these infants., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: This pilot study evaluated changes in regional cerebral oxygen saturation and cerebral blood flow volume during the transitional period in healthy term and moderately preterm infants., Methods: The cohort comprised 16 preterm infants and seven full-term infants with mean gestational ages of 34 and 39 weeks, respectively. Longitudinal measurements were conducted during the first three days after birth. Regional cerebral oxygen saturation was determined bilaterally by frequency domain near-infrared spectroscopy. Flow volumes were determined in internal carotid and vertebral arteries by multiplying the time-averaged velocity by the cross-sectional area: cerebral blood flow volume was calculated as the sum of flow volumes and adjusted for brain weight., Results: Brain weight-adjusted cerebral blood flow volumes and regional cerebral oxygen saturation were similar in preterm and term infants. Regional cerebral oxygen saturation did not correlate with brain weight-adjusted cerebral blood flow volume. Right and left brain weight-adjusted internal carotid flow volumes did not correlate with right and left regional cerebral oxygen saturation., Conclusion: Our findings suggest that during the first three days after birth there was adequate cardiorespiratory adaptation, cerebral perfusion and adequate compensation through the arterial circle of Willis in both healthy term and moderately preterm infants., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: For quick detection of neonatal early-onset bacterial infection (EOBI) pro-inflammatory cytokines like Interleukin-6 (IL-6) and Interleukin-8 (IL-8) in combiantion with C-reactive Protein (CRP) have been used. Automated determination of immature myeloid information (IMI) seems to be an additional useful tool in the diagnosis of NBI., Objective: To compare the diagnostic value of IMI, I/T-Ratio, plasma IL-6 and IL-8 levels and CRP in term and preterm neonates at time of clinical suspicion of EOBI., Patients and Methods: 31 preterm and 123 term neonates with clinical and serological signs of EOBI were analysed. 91 preterm and 159 term neonates with risk factors but without proven EOBI served as non-infected controls., Results: Neonates with EOBI showed significantly elevated IMI levels at time of first clinical suspicion of EOBI (Preterm: 1 028/µL (38-8 759) vs. 289/µL (6-3 126); Term: 1 268/µL (48-14 035) vs. 856/µL (19-5 735); p<0.05 respectively). I/T-Ratio, IL-6, IL-8 and CRP values were significantly higher in preterm and term neonates with EOBI (p<0.05). Sensitivity of IMI at a cut-off level of 650/µL was 84.2% [95%-CI: 74.0-91.6%] in preterm and 65.4% [95%-CI: 56.8-73.3%] in term infants. Specificity was 66.7% [95%-CI: 47.1-82.7%] and 53.9% [95%-CI: 43.8-63.7%], respectively. Combination of different infection parameters improved sensitivity up to 93.5% and specificity up to 98.9%., Conclusion: The diagnostic value of IMI in diagnosing EOBI in preterm and term neonates is not comparable to IL-6, IL-8 and CRP. Combination of IMI-Channel with IL-6, IL-8 or CRP improves their sensitivity, specificity and predictive value., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To compare oxygen saturations as displayed to caregivers on offset pulse oximeters in the 2 groups of the Canadian Oxygen Trial., Study Design: In 5 double-blind randomized trials of oxygen saturation targeting, displayed saturations between 88% and 92% were offset by 3% above or below the true values but returned to true values below 84% and above 96%. During the transition, displayed values remained static at 96% in the lower and at 84% in the higher target group during a 3% change in true saturations. In contrast, displayed values changed rapidly from 88% to 84% in the lower and from 92% to 96% in the higher target group during a 1% change in true saturations. We plotted the distributions of median displayed saturations on days with >12 hours of supplemental oxygen in 1075 Canadian Oxygen Trial participants to reconstruct what caregivers observed at the bedside., Results: The oximeter masking algorithm was associated with an increase in both stability and instability of displayed saturations that occurred during the transition between offset and true displayed values at opposite ends of the 2 target ranges. Caregivers maintained saturations at lower displayed values in the higher than in the lower target group. This differential management reduced the separation between the median true saturations in the 2 groups by approximately 3.5%., Conclusions: The design of the oximeter masking algorithm may have contributed to the smaller-than-expected separation between true saturations in the 2 study groups of recent saturation targeting trials in extremely preterm infants., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Snoring in children is a prevalent symptom and may be an indicator of obstructive sleep apnoea. Despite its importance, there is no national guideline on its appropriate management., Objective: To provide recommendations for the management of snoring in children and adolescents treated in a primary care setting., Methods: A total of 16 national paediatric sleep experts were included in a Delphi process and formulated recommendations in the form of a step-wise work-up procedure., Results: The following 8 steps were developed: (1) Identification of true cases of habitual snoring. (2) Identification of high-risk patients who should undergo polysomnography in a sleep laboratory. (3) Identification of mild cases that may be treated with anti-inflammatory medication. (4) Identification of cases that should be referred to an otorhinolaryngologist for potential surgery. (5) Performance of polysomnography in cases that remain unclear despite steps 3 and 4 to rule out obstructive sleep apnoea. (6) Reconsideration of surgery in cases with moderate to severe obstructive sleep apnoea. (7) Identification of severe sleep apnoea cases requiring continuous positive airway pressure therapy. (8) Identification of cases suitable for orthodontic treatment, craniofacial surgery or speech therapy., Conclusion: This guideline should help to improve the management of snoring children and adolescents in Germany.

Background: Adenotonsillar hyperplasia (ATH) can lead to severe breathing disorders, such as impaired nasal breathing, mouth breathing, snoring and obstructive sleep apnea. In such cases ATH should be treated mostly by performing adenoidectomy and/or adenotonsillectomy. There is increasing evidence that anti-inflammatory medication (AIM) is effective in treating ATH-related breathing disorders., Objectives: The aim of this study was to provide evidence and recommendations for the use of AIM in the treatment of ATH-related breathing disorders., Methods: In this study 12 national pediatric sleep experts were included into a Delphi process and formulated indications and recommendations., Results: The use of AIM in the treatment of ATH-related breathing disorders is sufficiently supported by the results of randomized controlled trials and systematic reviews. Nasal beclometason and nasal mometason have been studied for the treatment of enlarged adenoids and nasal fluticason and oral montelukast for the treatment of obstructive sleep apnea. The use of AIM for first-line treatment should be restricted to selected indications, such as a characteristic patient age and exclusion of an acute upper respiratory tract infection. Evidence-based recommendations are given concerning indications, dosage, treatment duration and correct administration of AIM., Conclusions: Anti-inflammatory medications are simple and effective alternatives for the treatment of ATH-related breathing disorders. These guidelines are intended to promote the use of AIM by pediatricians in ambulatory care settings.

Importance: The goal of oxygen therapy is to deliver sufficient oxygen to the tissues while minimizing oxygen toxicity and oxidative stress. It remains uncertain what values of arterial oxygen saturations achieve this balance in preterm infants., Objective: To compare the effects of targeting lower or higher arterial oxygen saturations on the rate of death or disability in extremely preterm infants., Design, Setting, and Participants: Randomized, double-blind trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel in which 1201 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days were enrolled within 24 hours after birth between December 2006 and August 2010. Follow-up assessments began in October 2008 and ended in August 2012., Interventions: Study participants were monitored until postmenstrual ages of 36 to 40 weeks with pulse oximeters that displayed saturations of either 3% above or below the true values. Caregivers adjusted the concentration of oxygen to achieve saturations between 88% and 92%, which produced 2 treatment groups with true target saturations of 85% to 89% (n = 602) or 91% to 95% (n = 599). Alarms were triggered when displayed saturations decreased to 86% or increased to 94%., Main Outcomes and Measures: The primary outcome was a composite of death, gross motor disability, cognitive or language delay, severe hearing loss, or bilateral blindness at a corrected age of 18 months. Secondary outcomes included retinopathy of prematurity and brain injury., Results: Of the 578 infants with adequate data for the primary outcome who were assigned to the lower target range, 298 (51.6%) died or survived with disability compared with 283 of the 569 infants (49.7%) assigned to the higher target range (odds ratio adjusted for center, 1.08; 95% CI, 0.85 to 1.37; P = .52). The rates of death were 16.6% for those in the 85% to 89% group and 15.3% for those in the 91% to 95% group (adjusted odds ratio, 1.11; 95% CI, 0.80 to 1.54; P = .54). Targeting lower saturations reduced the postmenstrual age at last use of oxygen therapy (adjusted mean difference, -0.8 weeks; 95% CI, -1.5 to -0.1; P = .03) but did not alter any other outcomes., Conclusion and Relevance: In extremely preterm infants, targeting oxygen saturations of 85% to 89% compared with 91% to 95% had no significant effect on the rate of death or disability at 18 months. These results may help determine the optimal target oxygen saturation., Trial Registrations: ISRCTN Identifier: 62491227; ClinicalTrials.gov Identifier: NCT00637169.

Background: The optimal rate of enteral feeding (EF) advancement in very low birth weight infants is under debate., Objectives: To evaluate the effects of accelerated EF advancement on the time to full enteral feeds, on early postnatal growth as well as on the frequency of necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) in very premature infants., Methods: In a retrospective single-center historic cohort study, infants with a gestational age <32 weeks at birth and birth weight <1,500 g, born between January 1, 2006, and December 31, 2007 (n = 136), were compared with infants born between January 1, 2010, and December 31, 2010 (n = 88). In 2006/2007, enteral feeds were initiated on day 1 with 10-15 ml/kg/day and advanced by 15-20 ml/kg/day. In 2010, enteral feeds were initiated with 20 ml/kg/day on day 1 and advanced by 25-30 ml/kg/day. Full enteral feeds were defined as ≥ 140 ml/kg/day. Data are presented as median (P25-P75)., Results: The time to establish full enteral feeds was shorter in 2010: 8 (7-11) days in 2006/2007 versus 6 (5-9) days in 2010. The incidences of NEC and FIP were 2.7 and 4.1% in 2006/2007 and 3.3 and 2.2% in 2010, respectively. Weight gain was not affected by the rate of EF advancement. Higher parenteral protein intake during week 1 in 2006/2007 was associated with better head circumference growth., Conclusions: The new approach was associated with a significantly shorter period to establish full enteral feeds. No difference in the incidence of FIP or NEC was observed; however, the study was underpowered to detect small but possibly important differences., (Copyright © 2012 S. Karger AG, Basel.)

Background: Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are major causes of morbidity in infants with extremely low birth weight (ELBW)., Objective: To evaluate the surgical procedures applied, and the survival and long-term outcome of ELBW infants with NEC and FIP in a single-center study., Methods: Inborn and outborn ELBW infants (<1000 g) with NEC and FIP were analyzed retrospectively from 2002 to 2007. Data collected include surgical procedures, survival as well as complications, length of partial parenteral nutrition and hospital stay. The short-term and long-term outcomes after 2-7 years were assessed and compared with a matched control group., Results: Out of 280 ELBW infants, 28 underwent surgery, 19 because of FIP and 9 for NEC. Fourteen infants in the FIP group were treated with primary laparotomy and 5 with peritoneal drainage (PD). In the NEC group, only 1 infant was treated with PD. PD was used for unstable patients and was always followed by secondary laparotomy after stabilization. Five of 28 (18%) surgically treated ELBW infants and 4 (14%) matched controls died. The following complications occurred in the surgical group: complete (n = 1) or minor wound dehiscence (n = 4), stoma prolapse (n = 5), parastomal hernia (n = 2), stoma fistula (n = 1), and wound infection (n = 2). Dependency on parenteral nutrition was significantly shorter in infants with FIP, while there were no differences in time to stoma closure and length of hospital stay between those with FIP and those with NEC. Eleven of 23 (47.8%) surviving patients with FIP or NEC showed developmental delay, compared with 9 of 24 (37.5%) in the controls., Conclusions: The management of EBLW infants with NEC and FIP remains challenging. Our treatment approach was associated with low mortality. Developmental delay seems to be caused by extreme prematurity rather than NEC- or FIP-related bowel perforation., (Copyright © 2012 S. Karger AG, Basel.)

Background: Since 2008, follow-up examinations at 2 years of age with the standardized Bayley II test have become obligatory in Germany for all very low birth weight infants., Aim: We already performed such examinations before 2006. Here, we compared our data and the completeness of our examinations before and after the introduction of the obligatory 2-year follow-up., Patients: From 2004-2007, 372 infants <1500 g or <32 weeks were discharged alive from our center, 19 infants died during their initial hospital stay, 2 after discharge., Results: 271 patients participated in the follow-up examination at age 2 years, with the proportion of participating infants increasing from 64% to 84% after the introduction of obligatory tests. 75% of infants showed a normal development, while 4% had a severe impairment (defined as being blind (1), deaf (1) or having cerebral palsy (6), the CP rate thus being 2%). 49% of infants completed the Bayley test; the mean MDI was 100.3 (SD 10.6). There were no significant qualtitative differences in test results with the introduction of the obligatory test., Conclusions: The completeness of our follow-up increased over the years. In comparison with international data we found a low rate of severely impaired, deaf or blind VLBW infants., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Pierre Robin Sequence (PRS) is characterised by mandibular micrognathia and/or retrognathia, glossoptosis and upper airway obstruction (UAO). In severe cases, UAO and cyanosis occur immediately after birth and endoscopic intubation may become necessary. Therefore, prenatal diagnosis with referral to a specialized department is important., Method: A non-invasive interdisciplinary treatment protocol is presented. The postnatal adjustment of the preepiglottic baton plate (PEBP) as early as possible is essential in this concept., Evidence: In a randomised cross-over trial with 11 patients with isolated PRS, the PEBP was found to reduce the apnoea index significantly and to be superior to a conventional palatal plate. An uncontrolled longitudinal study indicated that the UAO had normalised 3 months after discharge; all infants showed adequate weight gain with bottle feeding. In a comparative study with 34 healthy children and 34 children with isolated PRS, no significant differences in cognitive outcome was found., Conclusions: Interdisciplinary co-operation between prenatal care, neonatology and orthodontics is a pre-requisite for optimal postnatal therapy. Complications of UAO can be avoided by early and adequate treatment, resulting in good results for feeding, speech and facial profile. Invasive surgical treatment options like tongue-lip-adhesion, mandibular extension or distraction should be obsolete., (© Georg Thieme Verlag KG Stuttgart · New York.)

The authors report on a rare case of neonatal scrotal oedema occurring concurrently with pain upon palpation of the spermatic cord on the first day of life. An ultrasound examination showed poor perfusion of the left testicle and a thrombosis of the left renal vein; intraoperative exploration indicated necrosis of the left testicle without signs of torsion. Gorged vessels with paravasal bleeding were found in the spermatic cord. The authors hypothesise that necrosis of the testicle may result from haemorrhagic infarction caused by renal venous thrombosis. Acute scrotal discolouration with pain upon palpation in neonates is usually attributed to testicular torsion. The authors report a case where these symptoms had a different cause.

Background: To evaluate neonatal outcome, the German neonatal quality assurance dataset is often used. However, a systematic bias may occur, as not all live births are registered in this dataset. The aim of our study was to evaluate the magnitude of this systematic error by comparing this dataset to the national birth/death registry., Methods: The summary statistics of live births and deaths with a birthweight <1 500 g from the quality assurance datasets 2007-2009 of 5 German States (Baden-Württemberg, Bavaria, Hesse, Lower-Saxony and North Rhine-Westfalia) were compared with the dataset from the national birth/death registry., Results: Our analysis included 68% of the German birth cohort 2007-2009. The quality assurance dataset included 1 151 of 1 716 neonatal deaths (67.1%) in infants with a birthweight <1,000 g registered within the national birth/death registry; 565 deaths were missing. A total of 277 of 303 deaths (94.1%) with a birthweight 1,000-1,499 g were registered; 26 deaths were missing. In the state of Baden-Württemberg up to 11% more infants were registered in the quality assurance dataset than in the national registry, but an average of 36 neonatal deaths/year with a birthweight <1,000 g were missing (63.4% registration rate)., Conclusion: This analysis shows that the quality assurance data miss more than 1/3 of deaths in extremely low birthweight infants. Transfers between hospitals may result in multiple data entries and additional bias. Comparing outcome statistics based on the neonatal quality assurance dataset may lead to a substantial systematic error. Linkage to national birth and death certificates and/or to the perinatal dataset is urgently needed., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Aim: Preterm birth is the major cause of infant mortality and morbidity in both developed and developing countries. In Europe, the prevalence rate of premature birth ranges from 5.5 to 11.4% - an average of 7.1% of all live births. In this report, we aim to compare the current health and social policies, as well as practices in 13 EU member states., Materials and Methods: Using desk research, relevant information was gathered from each of the 13 European countries with regard to the prevalence of preterm birth, the cost of preterm birth to healthcare budgets, and the relevant policies, guidelines and practices in place at the national and, in some cases, regional level. The information comes from a range of sources, including government and parent association websites, published scientific literature and media reports., Results: Despite the growing prevalence and increasing costs, neonatal and preterm infant health rank low on the policy agendas of EU member states., Conclusion: Based on the findings, there are a number of recommendations that should be considered. The European Union should (i) recognize the growing challenge of prematurity in Europe and its significant impact on infant morbidity and mortality, (ii) improve neonatal health through the development and implementation of coordinated EU health and social policies, (iii) address the lack of comparable European data on prematurity, including prevalence, mortality, acute morbidity and long-term impairment, (iv) also increase the standard of neonatal care across Europe by supporting the development and implementation of European medical guidelines and quality standards, (v) support the development of European postgraduate training programmes in Peri- and Neonatology in order to increase the quality and availability of trained healthcare professionals., (© 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.)

The Pierre Robin sequence (PRS) characterized by mandibular micro- or retrognathia and glossoptosis with or without cleft palate, presents clinically with intermittent upper airway obstruction (UAO). It is associated with other malformations in about half the cases. The incidence is about 1:8,500. Isolated PRS without other malformations does not, by itself, appear to affect neurodevelopment. Active intervention may therefore be required to reduce the risk for neurocognitive impairment resulting from UAO. Current treatment options for UAO range from prone positioning, use of a nasopharyngeal tube, glossopexy via tongue lip adhesion, mandibular distraction to tracheostomy. An effective, non-invasive treatment protocol which includes implementation of an intraoral orthodontic appliance with velar extension (the pre-epiglottic baton plate; PEBP) is presented in this article., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: No survey has been published in recent years which primarily focuses on the prescription of inhaled corticosteroids in neonatal practice. Thus, the utilization rate of inhaled corticosteroids is unknown., Objectives: To elucidate the current utilization rate of inhaled corticosteroids in the prevention and therapy of bronchopulmonary dysplasia (BPD)., Methods: We developed an 18-item questionnaire that was distributed in March 2009, via electronic mail, to the pediatricians-in-chief of all the 343 German pediatric hospitals with a neonatal unit (all levels of neonatal care). We sent electronic reminders after 4 and 8 weeks., Results: 223 hospitals (65%) returned the questionnaire. Of these, 102 (46%) administered inhaled corticosteroids to premature infants either as prophylaxis or treatment for BPD. Predominantly, treatment with inhaled steroids was seen as a 'rescue therapy' and used only if other therapeutic approaches had failed. Of the hospitals not administering inhaled steroids, the most frequently stated reason was 'insufficient robust evidence to support benefit of therapy' (57%). In the majority of hospitals (81%), the active substance of choice was budesonide., Conclusions: Of the responders, approximately 50% administer inhaled corticosteroids to premature infants either as a prophylaxis or treatment for BPD. Lack of beneficial evidence was the main reason for not administering inhaled steroids in about half of the units which took this approach. Future trials should address this discrepancy by aiming to establish a clear benefit-risk ratio of inhaled corticosteroids., (Copyright © 2010 S. Karger AG, Basel.)

Preterm infants can inoculate virulent cytomegalovirus (CMV) through their mothers' raw breast milk. Complete virus inactivation is achieved only by heat treatment, but the effect on growth factors has never been assessed systematically. Insulin-like-growth-factor-1-, IGF-2-, insulin-like-growth-factor-binding-protein-2-, and IGFBP-3-concentrations were measured, before and after heating, in 51 breast-milk-samples from 28 mothers, and epidermal-growth-factor-concentrations in a subgroup of 35 samples from 22 mothers. Two heating methods were applied: Short-term (5 s) pasteurisation at 62, 65, and 72 degrees C, and long-term Holder-Pasteurisation (30 min) at 63 degrees C. IGF-1, IGF-2, IGFBP-2, and IGFBP-3 were measured by RIA, and EGF by ELISA. Heating for 30 min decreased significantly IGF-1 by 39.4%, IGF-2 by 9.9%, IGFBP-2 by 19.1%, and IGFBP-3 by 7.0%. In contrast, IGF-1, IGF-2, IGFBP-2, and IGFBP-3 were not altered significantly when using a short heating duration of 5 s, irrespective of the level of temperature, except for IGF-2 at 62 degrees C for 5 s (p = 0.041) and IGFBP-2 at 72 degrees C for 5 s (p = 0.025). Neither long- nor short-time heating methods changed the concentration of EGF. Only short heating methods (5 s, 62-72 degrees C) can preserve, almost completely, the concentrations of IGFs in human milk, whereas Holder-Pasteurization does not.

Supine sleeping is recommended to prevent the sudden infant death syndrome (SIDS). Low birth weight infants are at increased risk for SIDS, which is increased further if they are placed prone. Prone sleeping, however, also has advantages for preterm infants, such as a reduced apnoea rate, an increased lung volume and more quiet sleep. In their first weeks of life, these infants are usually on a monitor and under continuous observation. SIDS is extremely unlikely under these circumstances. Because of the aforementioned advantages, these infants may be placed prone during their first few weeks of life in the hospital. One week before discharge, however, they should be changed to back sleeping and the parents be explained that their baby is now nearing discharge and should thus be placed as it should also sleep at home: on its back and in a sleeping sack. We do not prescribe home monitors for SIDS prevention, but occasionally use pulse oximeters at home for a few weeks if an infant continues to exhibit apnoea of prematurity.

Bronchopulmonary dysplasia (BPD) is one of the most common long-term complications and treatment challenges in preterm infants. Theoretically, inhaled corticosteroids may suppress pulmonary inflammation without causing systemic side-effects, while bronchodilators will improve airway resistance and thereby work of breathing. This article reviews current data on these drugs in BPD prevention or treatment. Trials published to date have not demonstrated that regular bronchodilator administration influences the incidence of BPD or improves long-term outcome. Inhaled steroids started before 2 weeks of age may improve rates of successful extubation and reduce the need for rescue systemic glucocorticoids, but have not been shown to reduce the incidence of BPD. Thus, their use cannot be generally recommended. The data currently available are not sufficient to give any clearer recommendation on the use of these drugs in infants at high risk of, or established, BPD.

Background: Regionalization of perinatal and neonatal care improves outcome. The aim of this study was to compare outcome in preterm infants with a gestational age (GA) < 32 weeks in relation to patient volume., Methods: Outcome data from the state-wide neonatal quality assurance system from 2003 - 2004 from all infants treated in one of the five largest perinatal centers in Baden-Wuerttemberg were subtracted from the total dataset. Data derived from these five centers was compared with data from all other remaining NICU's in the state., Results: Mortality was 33.3 % vs. 15.0 % (other NICU's vs. five perinatal centers; p < 0.001) for infants < 26 weeks GA, 11.4 % vs. 8.9 % (n. s.) for infants 26 - 27 weeks GA, and 2.5 % vs. 3.5 % (n. s.) for infants 28 - 31 weeks GA. When analyzed as one group of infants < 28 weeks GA, mortality was 20.1 vs. 12.1 % (p = 0.003). The rate of intraventricular hemorrhage degrees III-IV was 30.2 % vs. 18.6 % (p = 0.015) for infants < 26 weeks GA, 14.5 % vs. 10.2 % (n. s.) for infants 26 - 27 weeks GA, and 2.9 % vs. 2.5 % (n. s.) for infants 28 - 31 weeks GA. The rate of periventricular leukomalacia was 11.3 % vs. 6.7 % (p = 0.18) for infants < 26 weeks GA, 6.1 % vs. 2.8 % (n. s.) for infants 26 - 27 weeks GA, and 2.8 % vs. 2.3 %; (n. s.) for infants 28 - 31 weeks GA., Conclusion: This study supports the hypothesis, that regionalization of neonatal care for very immature infants to few perinatal centers with a large case load may improve survival of these infants, and may reduce morbidity, associated with long-term sequelae.

To investigate the postnatal development of cerebral perfusion in preterm neonates with normal brains over the first 2 wk of life, a prospective longitudinal study was designed. Quantitative measurement of cerebral blood flow (CBF) volume was performed using ultrasound flowmetry of the extracranial, brain-feeding arteries in 32 preterm infants of 28-35 wk gestational age. Measurements were done in the internal carotid and vertebral arteries of both sides on d 1, 2, 3, 7, and 14 after birth. A 10.0-MHz linear transducer of a computed sonography system (Acuson 128/XP10) was used. Intravascular flow volumes were calculated as the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the vessel. Mean CBF volume increased markedly over the first 2 wk. One-third of this rise already occurred from the first to the second postnatal day, thereafter there was a continuous increase from d 2 to d 14 of life. Whereas the absolute level of CBF volume was primarily determined by postmenstrual age, the pattern of postnatal changes in CBF volume was found to be independent of gestational age. Arterial carbon dioxide tension, mean arterial blood pressure, and hematocrit had no influence on the development of CBF volume. The pronounced increase of CBF volume from d 1 to d 2 is likely to represent a normal adaptive response of the cerebral circulation to postnatal life. The data presented here may serve as the basis for further studies to investigate whether deviations from this adaptive response are associated with an increased risk of brain injury.