Hospital Regimens Including Probiotics Guide the Individual Development of the Gut Microbiome of Very Low Birth Weight Infants in the First Two Weeks of Life.

BACKGROUND: It is unknown to what extent the microbiome of preterm infants is influenced by hospital regimens including the use of different probiotics when it comes to the prevention of necrotizing enterocolitis (NEC). METHODS: Prospective controlled multicenter cohort study including very low birth weight infants from three neonatal intensive care units (NICUs) between October 2015 and March 2017. During this time span, stool was sampled every other day during the first two weeks and samples were subjected to amplicon-based microbiome analyses. Out of these, seventeen negative controls were processed (German Registry of Clinical Trials (No.: DRKS00009290)). RESULTS: The groups (3 × 18 infants) showed no statistically significant difference regarding gestational age, birth weight, APGAR scores and oxygen demand. 2029 different taxa were detected, including Enterococcus and Staphylococcus, as well as the probiotic genera Lactobacillus and Bifidobacterium predominating. The bacterial load was found to increase earlier on when probiotics were used. Without probiotics administration, Lactobacillus and Bifidobacterium contributed only marginally to the fecal microbiome. Some infants did not respond to probiotic administration. The samples from all centers participating reached a very similar diversity after two weeks while the microbiome samples from all three centers clustered significantly yet varied from each other. CONCLUSION: Probiotics proved to be safe and initiated an earlier increase of bacterial load (with marked individual divergences), which might play a crucial role in the prevention of neonatal morbidities. Meconium was found not to be free of bacterial DNA, and oral antibiotics did not influence the fecal microbiome development negatively, and hospital regimes led to a center-specific, distinct cluster formation.

Must screening examinations for retinopathy of prematurity necessarily be painful?

PURPOSE: This study investigates the impact of the length of the examination, the insertion of eyelid specula, and the indentation of the globe on the pain and stress sensation of premature infants. METHODS: Ninety-two premature infants in three neonatal wards were included. In two wards, the patients were examined using eyelid specula and scleral indentation as recommended in the official guidelines. In the third ward, the investigation time was minimized and ophthalmoscopy was performed without eyelid specula and scleral indentation. Physical and mental disturbance of the patients was assessed by the Neonatal Infant Pain Score and by monitoring the heart rate. The results were divided into two groups: in the one, eyelid specula and scleral indentation were used, whereas in the other one, they were not used. An independent-samples t-test was performed, which allowed us to calculate the correlation between the way the examination was executed and the condition of the patients. RESULTS: Demographic data and baseline values of heart rate and pain score did not differ between the two groups. Heart rate and pain score during and after the investigation were significantly higher and increased significantly with the duration of the examination for the patients who were investigated using lid specula and scleral indentation. CONCLUSION: Our study shows that indirect ophthalmoscopy without specula causes significantly less stress to infants than screening with lid specula and scleral indentation.

Changes of intestinal microbiota composition and diversity in very low birth weight infants related to strategies of NEC prophylaxis: protocol for an observational multicentre pilot study.

BACKGROUND: At the Division of Neonatology, Department of Paediatrics, Medical University Graz, a unique regimen of necrotizing enterocolitis (NEC) prophylaxis in preterm infants showing a < 1500 g birth weight (i.e. very low birth weight, VLBW) is used. The regimen includes oral antibiotic and antifungal therapy and probiotic preparations as well as a standardised feeding regimen. The incidence of NEC in preterm infants treated by this regimen has been shown to be lower, reflecting 0.7% when treatment was initiated on the first day of life, compared to international incidence rates (5.1%). However, the impact of the prophylaxis regimen on the intestinal microbiome is yet unknown. METHODS: We here report the protocol of an observational multicentre STROBE compliant pilot study in VLBW preterm infants. Research will compare three groups as defined by different NEC prophylaxis regimens. Each centre will provide 20 infants. Stool samples will be collected every 2 days throughout the first 2 weeks of life. Samples will be stored at - 80 °C until 16S-rRNA sequencing. 16S-rRNA genes will be amplified using suitable primers (specific for bacteria, fungi and archaea) and prepared for MiSeq Sequencing. Analyses will be performed using public analysis-pipelines, such as Mothur and Qiime, thus allowing an analysis of high-throughput community sequencing data. Abundance and composition changes in intestinal microbiota will be compared between the groups throughout the first 2 weeks of life. DISCUSSION: Different surroundings at the three participating study centres, including contacts to care takers and parents, as well as feeding or medication all might influence intestinal microbiota composition and abundance. In the planned sequel study, this should be kept in mind and a more standardised process ought to be established. However, the results obtained from the presented pilot study will display the burden of bias and help to establish a more strict protocol for the future. TRIAL REGISTRATION: Trial has been registered with the German Registry for Clinical Trials (registry ID DRKS00009290).

Mortality and morbidity in extremely preterm infants (22 to 26 weeks of gestation): Austria 1999-2001.

OBJECTIVE: The aim of this retrospective study was to analyze the mortality and morbidity for extremely preterm infants with a gestational age from 22 to 26 weeks. All infants were born in Austria during the years 1999-2001. METHODS: Data were collected from 16 neonatal intensive care units in Austria. Main outcome criteria were mortality, the rates of chronic lung disease (CLD) and severe retinopathy of prematurity (ROP, stage > or =3) to determine the short-term outcome; the rate of cerebral palsy (CP) at the corrected age of twelve months to assess the long-term outcome. RESULTS: Overall, 796 preterm infants with a gestational age less than 27 weeks were born in Austria and 581 (73%) were registered as live-born infants. Of those live born, 508 (87%) were analyzed. The mortality rates were 83%, 76%, 43%, 26% and 13% for 22, 23, 24, 25 and 26 weeks' gestation, respectively. The rates of CLD were 33% (22 weeks), 36% (23 weeks), 42% (24 weeks), 31% (25 weeks) and 22% (26 weeks). The rates of ROP of stage > or =3 were 0% (22 weeks), 29% (23 weeks), 23% (24 weeks), 18% (25 weeks) and 10% (26 weeks). The rates of CP at the corrected age of 12 months were 33%, 50%, 33%, 26% and 25% for 22, 23, 24, 25 and 26 weeks' gestation, respectively. CONCLUSIONS: The results of this national study are in accordance with the international literature: mortality and morbidity increased with decreasing gestational age.

Extended phenotypes in a boy and his mother with oto-palato-digital-syndrome type II.

We describe additional phenotypic features in a boy and his mother. Both manifested the phenotypic/genotypic correlation of oto-palato-digital syndrome type II. The mother's radiographs showed wormian bones of the skull, and paranasal bossing, her feet showed bilateral fusion of the cuboid with the lateral cuneiform bone with subsequent development of metatarsus varus associated with dysplastic distal phalanges.

Surfactant Protein B Deficiency Caused by Homozygous C248X Mutation-A Case Report and Review of the Literature.

Objective Surfactant protein B (SP-B) deficiency is a rare autosomal recessive disorder that is usually rapidly fatal. The c.397delCinsGAA mutation (121ins2) in exon 4 is found in more than two-thirds of patients. Design We report on a fatal case of SP-B deficiency caused by a homozygous C248X mutation in exon 7 of the SP-B gene. In addition, we provide an update of the current literature. The EMBASE, MEDLINE, and CINAHL databases were systematically searched to identify all papers published in the English and German literature on SP-B deficiency between 1989 and 2013. Results SP-B deficiency is characterized by progressive hypoxemic respiratory failure generally in full-term infants. They present with symptoms of respiratory distress and hypoxemia; chest X-ray resembles hyaline membrane disease. Prenatal diagnosis is possible from amniotic fluid or chorionic villi sampling. Conclusion Thirty-four mutations have been published in the literature. Treatment options are scarce. Gene therapy is hoped to be an option in the future.

Fetal MRI of a hypothalamic hamartoma in Pallister-Hall syndrome.

Fetal magnetic resonance imaging is increasingly being used as an adjunct to ultrasound. It allows for better visualization of in utero brain development and intracranial abnormalities (especially cerebral malformations). Hypothalamic hamartoma is a nonneoplastic malformation resembling normal hypothalamic tissue both histologically and on magnetic resonance imaging. Although it is rare, this entity is important to recognize for appropriate management and genetic counseling. We describe a unique patient in whom magnetic resonance imaging of the fetal brain allowed a prenatal diagnosis of Pallister-Hall syndrome.

[Connexin 26 mutation and keratitis-ichthyosis-deafness (KID) syndrome]. / Connexin-26-Mutation bei "Keratitis- Ichthyosis-Deafness"-Syndrom (KID-Syndrom).

BACKGROUND: Keratitis-ichthyosis-deafness syndrome (KID syndrome) is an extremely rare disorder. Inheritance is autosomal dominant but many cases occur sporadically following a spontaneous mutation. The cause of KID syndrome are missense mutations of the gene GJB2, encoding connexin 26. PATIENTS AND METHODS: We clinically studied two cases of KID syndrome and extracted genomic DNA from peripheral blood. RESULTS: The patients showed different heterozygous mutations of the connexin 26 gene and had quite different clinical courses. CONCLUSIONS: Both patients showed heterozygous mutations of the connexin 26 gene; a different Cx26 dominant mutation can cause a very different clinical course.

Axillary brachial plexus block for treatment of severe forearm ischemia after arterial cannulation in an extremely low birth-weight infant.

Severe limb ischemia after arterial catheterization in neonates and premature infants is a well-recognized problem. The usual treatment of ischemic injuries includes removal of the catheter and elevation of the effected limb. If unsuccessful, tissue necrosis and loss may follow. We report the case of a 700 g infant with severe distal forearm ischemia after right radial and ulnar artery catheterization. Immediate removal of the arterial line did not improve ischemia. Thirty-six hours later a brachial plexus block via the axillary approach with 0.5 ml bupivacaine 0.125% was performed resulting in rapid improvement, restricting ischemia eventually to fingers II-V as well as the distal part of the thumb. Brachial plexus blockade and active vasodilatation in tiny neonates after severe local ischemia are discussed.