Browsing by Subject "newborn"

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  • ALBINO Study Group; Maiwald, C.A.; Annink, K.V.; Rüdiger, M.; Benders, M.J.N.L.; Van Bel, F.; Allegaert, K.; Naulaers, G.; Bassler, D.; Klebermaß-Schrehof, K.; Vento, M.; Guimarães, H.; Stiris, T.; Cattarossi, L.; Metsäranta, M.; Vanhatalo, S.; Mazela, J.; Metsvaht, T.; Jacobs, Y. (2019)
    Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653,, May 22, 2017. © 2019 The Author(s).
  • BIOS Consortium; Reese, Sarah E.; Xu, Cheng-Jian; den Dekker, Herman T.; Lahti, Jari; Kajantie, Eero; Kere, Juha; Räikkönen, Katri (2019)
    Background: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. Objective: We sought to identify differential DNA methylation in newborns and children related to childhood asthma. Methods: Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions. Results: In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate <0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate <0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2. Conclusion: Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.
  • Acosta Leinonen, Johanna Natalia (Helsingin yliopisto, 2019)
    Sleep is one of the most vital functions of newborns and infants, and it is essential for neuronal network development. Therefore, long-term sleep disturbances have been associated with growth delays and behavioral disorders. Commonly reported infant sleep disturbances, such as night awakenings and difficulties falling asleep, cause distress to parents. Yet, the development of infant sleep in the home environment has not been fully elucidated due to lack of objective measurement parameters. In the current study, we assessed the feasibility of a motion sensor, attached to wearable pants, and ECG textile electrodes to monitor sleep-related respiration and heart rate of newborns and infants. First, we compared signals recorded by the motion sensor’s measurement channels to the standard respiratory piezo effort belt’s signal during daytime EEG recordings. According to our results, the motion sensor’s gyroscope proved to measure respiratory rate most accurately, while the ECG signal transmitted by the sensor was reliable in interpretable sections. We then provided wearable garments and smartphones to families with infants to assess overnight home-use. Our results indicate that different sleep states could likely be identified based on respiration fluctuation visible in the gyroscope’s signals. Moreover, the wearable system was considered practical and easy to use by the parents. Future studies should focus on validating the sensor with clinically approved measures, in order to train the algorithms to automatically identify different sleep-wake states. By doing so, the wearable sensor could provide information on natural infant sleep structure development over long time periods. Additionally, clinical validation of the sensor may result in the development of a companion diagnostic tool for infant cardiorespiratory and movement disorders.
  • Leppävirta, Jussi; Kallionpää, Roope A.; Uusitalo, Elina; Vahlberg, Tero; Pöyhönen, Minna; Peltonen, Juha; Peltonen, Sirkku (2019)
    Neurofibromatosis type 1 (NF1) is associated with reduced adult height, but there are no cohort studies on birth size. This retrospective study includes a cohort of 1,410 persons with NF1 and a matched comparison cohort from the general population. Figures for birth size were retrieved from the administrative registers of Finland, and the data were converted to standard deviation scores (SDS), defined as standard deviation difference to the reference population. The birth weight among infants with NF1 was higher than among infants without the disorder (adjusted mean difference [95% confidence interval]: 0.53 SDS [0.19-0.87]), as was the head circumference at birth (0.58 SDS [0.26-0.90]). The birth length of the NF1 infants did not differ significantly from the comparison cohort. The birth weight in the group consisting of NF1 and non-NF1 infants of NF1 mothers was lower than among infants of mothers in the comparison cohort (-0.28 SDS [-0.51 to -0.06]), as was the birth length (-0.22 SDS [-0.45 to 0.00]). In conclusion, the birth weight and head circumference of persons with NF1 are significantly higher than those of persons without the disorder. NF1 of the mother reduces birth weight and birth length of the infant.
  • Süvari, Liina; Janer, Cecilia; Helve, Otto; Kaskinen, Anu; Turpeinen, Ursula; Pitkänen-Argillander, Olli; Andersson, Sture (2019)
    IntroductionLung fluid clearance is essential for successful postnatal pulmonary adaptation. The epithelial sodium channel (ENaC) and Na-K-ATPase, induced by serum- and glucocorticoid-inducible kinase 1 (SGK1) as well as aquaporins (AQP), represent key players in the switch from fetal lung fluid secretion to absorption and in early postnatal lung fluid balance. Birth stress, including a surge in catecholamines, promotes pulmonary adaptation, likely through the augmentation of epithelial sodium reabsorption. ObjectivesWe sought to determine the changes in the airway gene expression of molecules vital to epithelial sodium transport during early pulmonary adaptation, and the association with birth stress reflected in the norepinephrine concentration in the cord blood in humans. MethodsWe included 70 term newborns: 28 born via vaginal delivery and 42 via elective cesarean section. We determined the norepinephrine concentrations in the cord blood using tandem mass spectrometry and collected nasal epithelial cell samples at 2min, 1h, and 24h postnatally to quantify ENaC, Na-K-ATPase, AQP5, and SGK1 mRNAs using RT-PCR. ResultsThe molecular gene expression involved in airway epithelium sodium transport changed markedly within the first hour postnatally. Newborns born via elective cesarean section exhibited a lower expression of ENaC, Na-K-ATPase, and SGK1. Significant correlations existed between the expressions of ENaC, Na-K-ATPase, and SGK1, and the concentration of norepinephrine in the cord blood. ConclusionsThe association of ENaC, Na-K-ATPase, and SGK1 expression with the cord blood norepinephrine concentration points to the importance of birth stress in promoting lung fluid clearance during early postnatal pulmonary adaptation.
  • Ahrapalo, Lotta (Helsingin yliopisto, 2018)
    Tämän tutkielman tarkoituksena on systemaattisen kirjallisuuskatsauksen kautta tarkastella vastasyntyneiden hengitysvaikeuksien non-invasiiviseen hoitoon liittyvää tutkimusnäyttöä. Suomessa syntyy vuosittain noin 50 000 lasta, joista 5-6 % ennenaikaisena. Täysiaikaisten ja keskosten tavallisimpia sairaalahoitoon johtavia syitä ovat hengitysvaikeudet, kuten keskosen hengitysvaikeusoireyhtymä tai täysiaikaisen ohimenevä hengitysvajaus. Hengitysvajaus johtuu keskosella keuhkojen ja hengityskeskuksen epäkypsyydestä ja täysiaikaisella syynä on usein keuhkonesteen hidas poistuminen. Hengitystä voidaan tukea joko invasiivisesti hengityskoneen avulla tai non-invasiivisin keinoin. Tämän katsauksen kannalta keskeisimpiä non-invasiivisia hengitystukimuotoja ovat nasaalinen ylipainetuki, nasaaliventilaattori ja korkeavirtausviikset. Hengityskonehoito on tehokas tapa avustaa hengitystä, mutta siihen liittyy vakavia haittoja, kuten hengitysteiden vaurioituminen, sepsis ja krooniset keuhkomuutokset. Nykysuositukset ohjaavat valitsemaan ensisijaisesti non-invasiivinen hengitystukimuodon, mikäli vastasyntyneen oma hengitys on riittävää. Non-invasiivisen tuen avulla voidaan lyhentää hengityskonehoidon kestoa käyttämällä sitä apuna koneesta vieroittumisessa tai tiettyjen potilaiden kohdalla konehoito pystytään välttämään kokonaan. Tutkimuksissa pyritään määrittämään ne potilaat, jotka kustakin hoitomuodosta hyötyvät. Tämän katsauksen tutkimukset osoittavat ylipaineen helpottavan ennenaikaisen vieroittumista hengityskonehoidosta pelkkää lisähappea paremmin. Nasaaliventilaattori vaikuttaa ylipainetta tehokkaammalta ja korkeavirtausviikset yhtä tehokkaalta hoidolta kuin ylipaine estämään hengityskoneeseen joutumista uudelleen. Keskosen hengitysvaikeusoireyhtymän ensilinjan hoidossa vastasyntyneisyyskaudella nasaaliventilaattori vaikutti ylipainetta tehokkaammalta, kun taas korkeavirtausviikset johtivat useammin hoidon epäonnistumiseen. Korkeavirtausviikset vaikuttivat soveltuvan parhaiten 30 raskausviikon jälkeen syntyneille, joiden lisähapentarve oli enintään 30 %. (194 sanaa)