CD55 Deficiency With Budd-Chiari Syndrome Treated by Liver Transplantation and Eculizumab.

We report the case of a male patient who had a history of early-onset protein-losing enteropathy, chronic diarrhea, and repeated thrombotic events since early childhood. He developed Budd-Chiari syndrome with consequent acute liver failure that required liver transplantation when he was 12 years old. The initial graft failed to function and he required retransplantation. Steroid-resistant rejection complicated the clinical course after the second transplant. Treatment with antithymocyte globulin stabilized graft function but abdominal symptoms and enteral protein loss persisted. The patient remained dependent on intravenous albumin and immunoglobulin. Extended work-up for thrombophilia was unremarkable. Flow cytometry analysis of the peripheral blood cells revealed an unexplained CD55 deficiency. By sequencing of CD55 and, later, exclusion of alternative rare diseases by whole-exome sequencing, we discovered a novel, likely pathogenic homozygous splice-site variant in CD55 c.578 + 5G>A, NM_000574.4, OMIM 125240. The staining of liver and colon biopsies revealed a lack of CD55 protein expression. After initiation of treatment with eculizumab, the patient achieved and has maintained a complete clinical remission throughout 56 months of follow-up. We recommend testing for CD55 deficiency in patients with protein-losing enteropathy. In addition, CD55 deficiency should be considered in the differential diagnosis of patients with Budd-Chiari syndrome in whom an underlying cause is uncertain.

Safety of the One Step Percutaneous Endoscopic Gastrostomy (Push-PEG) Button in Pediatric Patients.

OBJECTIVES: Percutaneous endoscopic gastrostomy (PEG)-systems are essential tools for enteral feeding in a broad variety of pediatric patients. The One Step ("Push-PEG") technique allows the direct introduction of a PEG-Button. The aim of the study was to investigate the safety and parental view of the Push-PEG technique. METHODS: We conducted a single-center retrospective data and questionnaire (SDC, http://links.lww.com/MPG/D296 ) based study including all pediatric patients receiving a PEG via push or pull technique between 2015 until end of 2020 and compared these 2 groups. The primary outcome was the detection of minor and major complications. Secondary outcomes were growth, thriving, and parental contentment using a Likert-scaled questionnaire. RESULTS: Eighty-three patients were included in the analysis. There were no significant differences in the basic data regarding age, weight, or diagnosis category. Overall complication rate was 34.9%. The Push-PEG group showed a lower rate of complications (32.7% vs 38.7%) and a lower rate of major complications (4.1% vs 8.8%), although the difference is not significant. Thirty-four families completed the questionnaire (SDC, http://links.lww.com/MPG/D296 ) (response rate 40%). There were no significant differences between the 2 groups regarding answers of the Likert-scaled questions. CONCLUSION: Push-PEG placement seems to be as safe as placement via traditional pull technique, even in small infants more than 2.8 months and 4 kg. As Push-PEG placement requires less follow-up interventions it may show significant advantages and could be the method of first choice in many cases.

Diseases associated with prematurity in correlation with N-terminal pro-brain natriuretic peptide levels during the early postnatal life.

The aim of this observational study was to investigate the influence of different typical preterm diseases on NT-proBNP serum levels in the early postnatal period of life of a preterm infant. NT-proBNP levels of 118 preterm infants born ≤ 31 weeks GA were determined at the first week of life, after 4 ± 1 weeks of life, and at a corrected gestational age of 36 + 2 weeks. Relevant complications with a possible influence on NT-proBNP values in the first week of life such as early neonatal infection, hemodynamically significant PDA (hsPDA), early pulmonary hypertension (early PH), and intraventricular hemorrhage (IVH) were evaluated; at 4 ± 1 weeks of life, bronchopulmonary dysplasia (BPD), BPD-related pulmonary hypertension (BPD-associated PH), late infection, IVH, and intestinal complications were evaluated. At a corrected gestational age of 36 ± 2 weeks, we examined the effect of retinopathy of prematurity (ROP), BPD, BPD-associated PH, and late infection on NT-proBNP levels. In the first days of life, only the isolated occurrence of hsPDA resulted in significantly increased NT-proBNP levels. In multiple linear regression analysis, early infection remained independently associated with NT-proBNP levels. At 4 ± 1 weeks of age, the isolated presence of BPD and BPD-related PH resulted in increased levels, and the effect remained significant in the multiple regression analysis. At a corrected gestational age of 36 ± 2 weeks, infants with relevant complications at this final evaluation time tended to have lower NT-proBNP values than our exploratory reference values.    Conlusion: NT-proBNP in the first week of life seems to be mainly influenced by an hsPDA and infection or inflammation. BPD and BPD-related PH are the most important factors influencing NT-proBNP serum levels in the first month of life. When preterm infants reach a corrected GA of 36 ± 2 weeks, chronological age rather than complications of prematurity must be considered when interpreting NT-proBNP levels. What is Known: • Several complications associated with prematurity, such as hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been shown to influence NT-proBNP levels in preterm infants in their early postnatal life. What is New: • Hemodynamically relevant PDA is a major factor in the increase of NT-proBNP levels in the first week of life. • Bronchopulmonary dysplasia and pulmonary hypertension associated with bronchopulmonary dysplasia are important factors in the increase in NT-proBNP levels in preterm infants at approximately 1 month of age.

Microbiome analysis and fecal microbiota transfer in pediatric gastroenterology - a structured online survey in German-speaking countries.

PURPOSE: To assess the current attitude and the status quo towards the use of microbiome analysis and fecal microbiota transfer (FMT) in pediatric patients in German-speaking pediatric gastroenterology centers. METHODS: A structured online survey among all certified facilities of the German-speaking society of pediatric gastroenterology and nutrition (GPGE) was conducted from November 01, 2020, until March 30, 2021. RESULTS: A total of 71 centers were included in the analysis. Twenty-two centers (31.0%) use diagnostic microbiome analysis, but only a few perform analysis frequently (2; 2.8%) or regularly (1; 1.4%). Eleven centers (15.5%) have performed FMT as a therapeutic approach. Most of these centers use individual in-house donor screening programs (61.5%). One-third (33.8%) of centers rate the therapeutic impact of FMT as high or moderate. More than two-thirds (69.0%) of all participants are willing to participate in studies assessing the therapeutic effect of FMT. CONCLUSIONS: Guidelines for microbiome analyses and FMT in pediatric patients and clinical studies investigating their benefits are absolutely necessary to improve the patient-centered care in pediatric gastroenterology. The long-term and successful establishment of pediatric FMT centers with standardized procedures for patient selection, donor screening, application route, volume, and frequency of use is highly required to obtain a safe therapy.

Effective high-throughput RT-qPCR screening for SARS-CoV-2 infections in children.

Systematic SARS-CoV-2 testing is a valuable tool for infection control and surveillance. However, broad application of high sensitive RT-qPCR testing in children is often hampered due to unpleasant sample collection, limited RT-qPCR capacities and high costs. Here, we developed a high-throughput approach ('Lolli-Method') for SARS-CoV-2 detection in children, combining non-invasive sample collection with an RT-qPCR-pool testing strategy. SARS-CoV-2 infections were diagnosed with sensitivities of 100% and 93.9% when viral loads were >106 copies/ml and >103 copies/ml in corresponding Naso-/Oropharyngeal-swabs, respectively. For effective application of the Lolli-Method in schools and daycare facilities, SEIR-modeling indicated a preferred frequency of two tests per week. The developed test strategy was implemented in 3,700 schools and 698 daycare facilities in Germany, screening over 800,000 individuals twice per week. In a period of 3 months, 6,364 pool-RT-qPCRs tested positive (0.64%), ranging from 0.05% to 2.61% per week. Notably, infections correlated with local SARS-CoV-2 incidences and with a school social deprivation index. Moreover, in comparison with the alpha variant, statistical modeling revealed a 36.8% increase for multiple (≥2 children) infections per class following infections with the delta variant. We conclude that the Lolli-Method is a powerful tool for SARS-CoV-2 surveillance and can support infection control in schools and daycare facilities.

[Fecal Microbiota Transfer (FMT) in Children and Adolescents - Review and statement by the GPGE microbiome working group]. / Fäkaler Mikrobiota Transfer (FMT) bei Kindern und Jugendlichen ­ Review und Stellungnahme der GPGE AG Mikrobiom.

The human microbiome and especially the gastrointestinal microbiota are associated with health and disease. Disturbance in the composition or function of fecal microbiota (dysbiosis) plays a role in the development of pediatric gastrointestinal diseases. Fecal microbiota transfer (FMT) is a special intervention, where microbiota are transferred from a healthy donor.In this review we describe the current state of knowledge for FMT in pediatric patients. There is satisfactory evidence concerning FMT in patients with recurrent C. difficile infection. For inflammatory bowel disease, few studies show a potential benefit.Adverse events occurred frequently in clinical studies, but were mostly mild and transient. There are hardly any data on long-term side effects of FMT, which are particularly significant for pediatrics. In practice, there is uncertainty as to which application route, dosage or frequency should be used. Legally, donor stool is considered a drug in German-speaking countries, for which no marketing authorization exists.In conclusion, knowledge about physiology, efficacy and side effects of FMT is insufficient and legal concerns complicate its implementation. More studies on this topic are needed urgently.

Assessment of whole gut motility in adolescents using the wireless motility capsule test.

Functional gastrointestinal (GI) disorders are often associated with intestinal dysmotility representing a diagnostic challenge. A relatively new method is the wireless motility capsule (WMC) test, which continuously measures pH, pressure, temperature and regional transit times as it passes through the GI tract. In adults, the WMC test was approved for use in the diagnosis of gastroparesis and constipation by assessing GI transit and contractility. We performed the WMC test in nine adolescent patients aged 12-17 years with functional GI symptoms from July 2017 until February 2019. Abnormal transit times were detected in four patients. Three patients showed abnormal transit times of the upper GI tract: in two cases, contractility analysis revealed prolonged gastric retention, and in one patient, abnormal colonic transit was detected.Conclusion: The WMC test is a minimally invasive procedure with potential to expand future diagnostic opportunities for paediatric patients with functional GI disorders and suspected motility disturbances. What is Known: • The assessment of GI transit and contractility of the whole gut is possible with the WMC test which is approved for use in the diagnosis of gastroparesis and constipation in adults. What is New: • The WMC test is a non-invasive diagnostic tool with the potential to expand diagnostic opportunities in paediatric patients by assessing regional and whole gut motility. • In paediatric patients with functional GI disorders, the WMC test could help to make an adequate diagnosis and initiate appropriate therapy.

Maternal Exercise Mediates Hepatic Metabolic Programming via Activation of AMPK-PGC1α Axis in the Offspring of Obese Mothers.

Maternal obesity is associated with an increased risk of hepatic metabolic dysfunction for both mother and offspring and targeted interventions to address this growing metabolic disease burden are urgently needed. This study investigates whether maternal exercise (ME) could reverse the detrimental effects of hepatic metabolic dysfunction in obese dams and their offspring while focusing on the AMP-activated protein kinase (AMPK), representing a key regulator of hepatic metabolism. In a mouse model of maternal western-style-diet (WSD)-induced obesity, we established an exercise intervention of voluntary wheel-running before and during pregnancy and analyzed its effects on hepatic energy metabolism during developmental organ programming. ME prevented WSD-induced hepatic steatosis in obese dams by alterations of key hepatic metabolic processes, including activation of hepatic ß-oxidation and inhibition of lipogenesis following increased AMPK and peroxisome-proliferator-activated-receptor-γ-coactivator-1α (PGC-1α)-signaling. Offspring of exercised dams exhibited a comparable hepatic metabolic signature to their mothers with increased AMPK-PGC1α-activity and beneficial changes in hepatic lipid metabolism and were protected from WSD-induced adipose tissue accumulation and hepatic steatosis in later life. In conclusion, this study demonstrates that ME provides a promising strategy to improve the metabolic health of both obese mothers and their offspring and highlights AMPK as a potential metabolic target for therapeutic interventions.

Reference values for N-terminal Pro-brain natriuretic peptide in premature infants during their first weeks of life.

The aim of our study was to observe the temporal distribution of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in premature infants of ≤ 31 weeks of gestational age (GA) during the first weeks of life. NT-proBNP values of 118 preterm infants born ≤ 31 weeks GA were determined during the first week of life, after 4 ± 1 weeks of life, and at a corrected GA of 36 ± 2 weeks. Infants were divided into two groups: those without relevant complications and those with complications related to prematurity. NT-proBNP values of infants without complications define our exploratory reference values. The Median NT-proBNP level of these infants was 1896 ng/l (n = 27, interquartile range (IQR): 1277-5200) during the first week of life, 463 ng/l (n = 26, IQR: 364-704) at 4 ± 1 weeks of life, and 824 ng/l (n = 33, IQR: 714-1233) at a corrected GA of 36 ± 2 weeks. Infants born < 28 + 0 weeks GA had significantly higher NT-proBNP values (n = 9, median: 5200, IQR: 1750-8972) than infants born ≥ 28 + 0-31 weeks GA (n = 18, median: 1528, IQR: 838-3052; p = 0.017). Growth restriction or PDA status could not account for the difference in NT-proBNP values between GA groups.Conclusions: The results of our observational and cross-sectional study describe exploratory reference values for NT-proBNP levels in preterm infants of ≤ 31 weeks GA according to postnatal age. NT-proBNP levels during the first week of life are high and widely distributed in preterm infants and decrease subsequently to reach a distinctly lower and stable plateau at around 1 month of life. Our results suggest an influence of GA on NT-proBNP values in the first week of life. What is Known: • Several complications related to prematurity, e.g., hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been associated with a temporary rise in NT-proBNP values in preterm infants during their first weeks of life. What is New: • This observational study provides reference values for NT-proBNP levels of very and extremely preterm infants during their first weeks of life. • In premature infants without complications, NT-proBNP values during their first week of life depend on gestational age at birth.

Effects of ketamine on neurogenesis, extracellular matrix homeostasis and proliferation in hypoxia-exposed HT22 murine hippocampal neurons.

Ketamine is a widely used drug in pediatric anesthesia, and both neurotoxic and neuroprotective effects have been associated with its use. There are only a few studies to date which have examined the effects of ketamine on neurons under hypoxic conditions, which may lead to severe brain damage and poor neurocognitive outcomes in neonates. In the present study, the effects of ketamine on cellular pathways associated with neurogenesis, extracellular matrix homeostasis and proliferation were examined in vitro in hypoxia-exposed neurons. Differentiated HT22 murine hippocampal neurons were treated with 1, 10 and 20 µM ketamine and cultured under hypoxic or normoxic conditions for 24 h followed by quantitative PCR analysis of relevant candidate genes. Ketamine treatment did not exert any notable effects on the mRNA expression levels of markers of neurogenesis (neuronal growth factor and syndecan 1), extracellular matrix homeostasis (matrix-metalloproteinase 2 and 9, tenascin C and tenascin R) or proliferation markers (Ki67 and proliferating cell nuclear antigen) compared with the respective untreated controls. However, there was a tendency towards downregulation of multiple cellular markers under hypoxic conditions and simultaneous ketamine treatment. No dose-dependent association was found in the ketamine treated groups for genetic markers of neurogenesis, extracellular matrix homeostasis or proliferation. Based on the results, ketamine may have increased the vulnerability of hippocampal neurons in vitro to hypoxia, independent of the dose. The results of the present study contribute to the ongoing discussion on the safety concerns around ketamine use in pediatric clinical practice from a laboratory perspective.

Mutations in plasmalemma vesicle-associated protein cause severe syndromic protein-losing enteropathy.

BACKGROUND: Protein-losing enteropathy (PLE) is characterised by gastrointestinal protein leakage due to loss of mucosal integrity or lymphatic abnormalities. PLE can manifest as congenital diarrhoea and should be differentiated from other congenital diarrhoeal disorders. Primary PLEs are genetically heterogeneous and the underlying genetic defects are currently emerging. OBJECTIVES: We report an infant with fatal PLE for whom we aimed to uncover the underlying pathogenic mutation. METHODS: We performed whole exome sequencing (WES) for the index patient. Variants were classified based on the American College of Medical Genetics and Genomics guidelines. WES results and our detailed clinical description of the patient were compared with the literature. RESULTS: We discovered a novel homozygous stop mutation (c.988C>T, p.Q330*) in the Plasmalemma Vesicle-Associated Protein (PLVAP) gene in a newborn with fatal PLE, facial dysmorphism, and renal, ocular and cardiac anomalies. The Q330* mutation is predicted to result in complete loss of PLVAP protein expression leading to deletion of the diaphragms of endothelial fenestrae, resulting in plasma protein extravasation and PLE. Recently, another single homozygous stop mutation in PLVAP causing lethal PLE in an infant was reported. CONCLUSIONS: Our findings validate PLVAP mutations as a cause of syndromic PLE. Prenatal anomalies, severe PLE and syndromic features may guide the diagnosis of this rare disease.

Peritoneal drainage in pneumoperitoneum in extremely low birth weight infants.

The aim was to determine if peritoneal drainage (PD) is a suitable treatment for pneumoperitoneum in extremely low birth weight (ELBW) infants. A retrospective chart review of 42 ELBW infants with pneumoperitoneum at the University Hospital of Cologne between November 2014 and April 2017 was performed. Forty-two infants with a median birth weight of 645 g (interquartile range (IQR) 550, 806) and a median gestational age of 24.3 weeks (IQR 23.2, 25.6) were treated for pneumoperitoneum. Twenty-six (62%) received PD, and in ten (38%), the drain could be removed without further intervention. Infants in the PD group were of significantly lower birth weight (622g vs. 750 g), age (4.5 vs. 10.0 days), and weight at diagnosis (538 vs. 778 g). The mortality in the PD group was 15% at 90 days of life, but no patient deceased in the primary laparotomy group. CONCLUSION: We suggest PD with close evaluation of drainage and clinical course as an alternative treatment for pneumoperitoneum in ELBW infants allowing bridging the vulnerable first days of life until these infants are in a more stable condition. Despite not reaching statistical significance in our series, PD showed the trend towards higher mortality. What is known: • Pneumoperitoneum is traditionally treated with laparotomy, but placement of peritoneal drainage (PD) is a valuable treatment option. • Previous randomized controlled trials have shown no significant differences in mortality for PD versus laparotomy. What is new: • In our cohort, 38% of the infants with PD could be saved from secondary laparotomy, but in the PD group there was a trend towards higher mortality. • PD allows bridging the vulnerable first days of life until ELBW infants are in a more stable condition for possible laparotomy.

The flexion withdrawal reflex increases in premature infants at 22-26 weeks of gestation due to changes in spinal cord excitability.

AIM: Our aim was to study the development of the cutaneous flexion withdrawal reflex among premature infants admitted to the neonatal intensive care unit of the Children's Hospital, University of Cologne, in 2013. METHODOLOGY: This longitudinal cohort study explored the development of spinal cord excitability of 19 premature infants born at 22-26 weeks of gestation. We performed five investigations per subject and studied changes in the reflex threshold with increasing postnatal age at different behavioural states. The premature infants were stimulated with von Frey filaments on the plantar surface of the foot near the first metatarsophalangeal joint during the first 3 days of life and at postnatal ages of 10-14 days, 21-28 days, 49-59 days and a corrected gestational age of 37-40 weeks. RESULTS: The mean gestational age of the premature infants included in the study was 24 weeks. Premature infants with a gestational age of less than 26 weeks presented a flexion withdrawal reflex with a low threshold (0.5-2.85 milli-Newton) in the first 72 hours of life. CONCLUSION: The flexion withdrawal reflex among premature infants born at less than 26 weeks showed a continuous threshold increase with increasing postnatal age, reflecting changes in spinal cord excitability.

Pain-Related Reactions among Premature Infants with Gestational Age Less than 26 Weeks: An Observational Cohort Study.

INTRODUCTION: There is insufficient information regarding acute pain reactions among premature infants with a gestational age of less than 26 weeks and no appropriate scale for pain measurement in this age group. We hypothesized that these infants present specific reactions to a standardized pain stimulus within the first 3 days of life. METHODOLOGY: Mixed-methods, prospective, open-label, single-arm, observational study. Routine capillary or peripheral blood takes were filmed. The model consisting of a baseline, a preparatory, an interventional and a return-to-baseline phase was filmed. After a pilot evaluation, experienced medical and nursing neonatal intensive care unit (NICU) staff analysed the videos. RESULTS: Twenty infants with gestational ages ranging from 22 weeks and 3 days to 26 weeks (mean 24 weeks) were recruited. Nineteen infants showed pain reactions, with a mean latency of 8.3 s (range 2-30). The majority presented eye movements, changes of the breath pattern and a slight increase in the mean SpO2 value. A high degree of interrater and intrarater reliability was found. DISCUSSION: Premature infants with a gestational age of up to 26 weeks can present a variety of discrete reactions as response to a pain stimulus within the first 72 h of life. Experienced NICU staff can perform a valid and reliable evaluation of these reactions.

Skin conductance in neonates suffering from abstinence syndrome and unexposed newborns.

UNLABELLED: The aims of this study were to compare the skin conductance (SC) of newborns with opiate-induced neonatal abstinence syndrome (NAS) to that of unexposed newborns and to evaluate the potential of SC readings to detect distress in the context of NAS objectively. The SC of 12 newborns with NAS and 12 unexposed newborns was measured at nine specific times during their first 6 weeks of life. The number of SC fluctuations per second (NSCF/s), the amplitude of SC fluctuation, and the mean level of SC were recorded and analyzed. The SC of newborns treated for symptoms of NAS differed significantly from the SC of unexposed newborns with regard to the NSCF/s (p = 0.04). With the mean level of SC, we observed an interaction between groups over time (p value for interaction = 0.02). With increasing postnatal age, we observed higher values in all three SC parameters. CONCLUSION: The NSCF/s and the mean level of SC appear to be suitable to reflect the distress of newborns suffering from NAS. As it is known that the sensitivity of SC increases with the level of stress experienced, its potential to indicate elevated stress levels in infants with NAS should be investigated in future studies evaluating different therapy regimens. WHAT IS KNOWN: • Skin conductance is a result of the filling of palmar and plantar sweat glands innervated by the sympathetic nervous system • Skin conductance can be used as a measure of stress and pain in newborns What is New: • Skin conductance of newborns with neonatal abstinence syndrome (NAS) differs significantly from the SC of non-substance-exposed newborns during the first 6 weeks of life • Skin conductance appears to reflect the increased distress of infants with NAS.

Multidimensional response to vaccination pain in very preterm, moderate- to-late preterm and full-term infants at age three months.

BACKGROUND: Very early life pain exposure and stress induces alterations in the developing brain and leads to altered pain sensitivity. In premature infants with a history of numerous early postnatal adverse events, behavioral responsiveness and hypothalamic-pituitary-adrenal (HPA) axis reactivity may show alterations as well. AIMS: We compared a multidimensional response to a painful situation (vaccination) in three month old infants. The study involved very preterm, moderate to late preterm infants and full-term infants with varying exposure to pain and stress within the first weeks of life. STUDY DESIGN: At the age of three months, we evaluated the infants' reactivity to intramuscular injections for immunization. SUBJECTS: The study included 61 very preterm infants, 30 moderate to late preterm infants and 30 full-term infants. OUTCOME MEASURES: We assessed heart rate recovery, Bernese pain Score and increase of salivary cortisol following vaccination. We also evaluated the flexor withdrawal reflex threshold as well as Prechtl's General Movements. Secondly, we assessed factors potentially influencing pain reactivity such as exposure to pain/stress, gender, use of steroids or opioids and mechanical ventilation. RESULTS: Very preterm, moderate to late preterm and full-term infants showed different reactivity to pain in all analyzed aspects. Very preterm infants showed a lower level of behavioral and physiologic reactivity and exposure to pain/stress predicted lower cortisol increase. CONCLUSION: At three months of age, very preterm infants show an altered level of HPA axis reactivity. Efforts aiming at minimizing pain and stress in premature infants should be taken.

Oral glucose in preterm neonates during oropharyngeal suctioning: a randomized controlled cross-over trial.

UNLABELLED: To investigate whether orally applied glucose reduces pain response during oropharyngeal suctioning in preterm infants with a birth weight >1500 g, we conducted a randomized, double-blind, placebo-controlled cross-over trial on 32 preterm infants undergoing oropharyngeal suctioning while on nasal continuous positive airway pressure (CPAP). The Premature Infant Pain Profile (PIPP) score was assessed and compared in a cross-over design to investigate whether there was a significant difference in the patients' pain response. The mean PIPP score during oropharyngeal suctioning after placebo was 8.6 (KI 7.8-9.4). After glucose administration, the mean PIPP score was 8.0 (KI 7.1-8.9). Comparison of the treatment effects reached no statistic significance (p = 0.23). During the oral study drug administration during nasal CPAP, we observed 47 adverse events, but none necessitated therapeutic intervention and none was classified as serious. CONCLUSION: In our study, late preterm infants in the first days of life did not benefit significantly from analgesia with glucose during oropharyngeal suctioning. The oral administration of glucose under nasal CPAP led to no serious adverse events.

Increased rate of parental postpartum depression and traumatization in moderate and late preterm infants is independent of the infant's motor repertoire.

BACKGROUND: Moderately and late preterm infants represent a considerable and increasing proportion of infants cared for in neonatal departments worldwide. Parents of preterm infants are at risk of postpartal depression (PPD) and posttraumatic stress disorder (PTSD), and preterm infants are at risk of developmental impairment. AIM: This study aimed to assess (1) the incidence of parental PPD and PTSD in moderate to late preterm infants in comparison to full-term infants and (2) the influence of infants' motor repertoire assessed by Prechtl's general movements and illness severity on parental PPD and PTSD. SUBJECTS: We studied 60 mothers and 56 fathers of 69 preterm infants (born at 32 to 37 weeks of gestation) and 32 mothers and 29 fathers of 34 full-term infants. OUTCOME MEASURES: We assessed the incidence of parental PPD, PTSD and perceived social support as well as infants' illness severity and motor repertoire at birth, term and 3 months corrected age. RESULTS: Preterm mothers and fathers had significant higher depression scores after birth compared to full-term parents (p=0.033 and 0.021). Preterm fathers also had higher traumatization scores compared to full-term fathers (p=0.007). Probable or possible PPD/PTSD was not associated with infant's illness severity or quality of motor repertoire. No differences in motor development were found between preterm and full-term infants. CONCLUSION: Moderate to late preterm infants' parents are at increased risk for PPD irrespective of infants' motor repertoire or illness severity.

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.