Oxidative stress - Related spontaneous preterm delivery challenges in causality determination, prevention and novel strategies in reduction of the sequelae

Spontaneous preterm birth (PTB) is one of the major complications of pregnancy and the main cause of neonatal mortality and morbidity. Despite the efforts devoted to the understanding of this obstetrical syndrome and improved medical care, there has been a tendency for the PTB rate to increase in the last decades globally. The costs of the screening for spontaneous PTB, its management, and treatment of the sequelae represent a major burden to the health service economy of high-income countries. In this scenario, it has been widely acknowledged that oxidative stress (OS) plays an important role in the pathogenicity of human disease in wide range of areas of medicine. There is an emerging evidence that an imbalance between pro-and-antioxidants may be associated with spontaneous PTB. However, there are still many controversies on the mechanisms by which OS are involved in the pathogenesis of prematurity. Moreover, the crucial question whether the OS is the cause or consequence of the disease is yet to be answered. The purpose of this article is to briefly summarize the current knowledge and controversies on oxidative stress-related spontaneous PTB and to give a critical approach on future perspectives on this topic as a classical example of translational medicine. Placenta-mediated pregnancy adverse outcome associated with OS leading to iatrogenic PTB (e.g. pre-eclampsia, intrauterine growth restriction, gestational diabetes) will not be discussed.Peer reviewe

Caffeine is a respiratory stimulant without effect on sleep in the short-term in late-preterm infants

Publisher Copyright: © 2021, The Author(s).Background Caffeine is widely used in preterm infants for apnea control. It has no effect on sleep in the only existing polysomnographic study including ten preterm infants Behavioral and polygraphic studies have conflicting results. Methods We studied 21 late-preterm infants at a median gestational age of 36 weeks. Polysomnography was performed twice, at baseline on day 1 and on the day after the onset of caffeine treatment (20 mg/kg loading and 5 mg/kg morning maintenance dose). Results Caffeine acted short term as a breathing stimulant with reduction of apneas, improved baseline SpO(2) (p < 0.001), and decreased 95 percentile of end-tidal carbon dioxide level (p < 0.01). It also increased arousal frequency to SpO(2) desaturations of more than 5% (p < 0.001). Caffeine did not affect sleep stage distribution, sleep efficiency, frequency of sleep stage transitions, appearance of REM periods, or the high number of spontaneous arousals. The median spontaneous arousal count was 18 per hour at baseline, and 16 per hour during caffeine treatment (p = 0.88). Conclusions In late-preterm infants, caffeine has a clear short-term respiratory stimulant effect, and it increases the arousal frequency to hypoxia. However, caffeine does not appear to act as a central nervous system stimulant, and it has no acute effect on sleep quality. Impact Effects of caffeine on sleep in preterm infants has previously been investigated with only one full polysomnographic study including ten preterm infants. The study showed no effect. The current study shows that caffeine acts short term as a respiratory stimulant and increases arousal frequency to hypoxia. Although a potent central nervous system (CNS) stimulant in adults, caffeine does not seem to have similar acute CNS effect in late-preterm infants. The onset of caffeine treatment has no short-term effect on sleep stage distribution, sleep efficiency, frequency of sleep stage transitions, appearance of REM periods, or the high number of spontaneous arousals.Peer reviewe

Supplemental Oxygen Treats Periodic Breathing without Effects on Sleep in Late-Preterm Infants

Background: The effect of supplemental oxygen on sleep has not been studied in preterm infants. Methods: We studied 18 stable late-preterm infants with observed periodic breathing at a median gestational age of 36 weeks. Polysomnography was performed on room air and on 25% oxygen-enriched ambient air. Results: Supplemental oxygen did not affect sleep stage distribution, sleep efficiency, the frequency of sleep stage transitions, the appearance of rapid-eye movement (REM) sleep periods, or the high number of spontaneous arousals. The percentage in periodic breathing out of total sleep time decreased from 10% (interquartile range [IQR] 5-9%) on room air to 1% (IQR 0-3%) (p < 0.001) on supplemental oxygen. Also, the number of central apneas decreased from 48 (IQR 32-68) to 23 (IRQ 15-32) per hour (p < 0.001), and the number of oxygen desaturations of a minimum 3% from 38 (IQR 29-74) to 10 (IQR 5-24) per hour (p < 0.001). On room air in non-REM sleep, the median end-tidal carbon dioxide values were systematically lower during periodic breathing at 5.1 (IQR 4.6-6.4) kPa than during stable breathing at 5.5 (4.9-5.9) kPa (p < 0.0001). Conclusions: In late-preterm infants, supplemental oxygen effectively reduces periodic breathing and the number of oxygen desaturations while having no significant effect on sleep. The results support the importance of carotid body over-reactivity on the genesis of periodic breathing in preterm infants.Peer reviewe

Tekoäly vastasyntyneiden tehohoidossa

Vertaisarvioitu. English summary. Teema : tekoäly lääketieteessä.Sähköisessä muodossa oleva lääketieteellinen tieto lisääntyy jatkuvasti, ja erityisesti tehohoidossa olevien potilaiden hoidosta pystytään integroitujen mittalaitteiden ansiosta muodostamaan potilastietojärjestelmiin yhä kattavampi kuva. Yhdistämällä nämä tiedot terveydenhuollon rekistereihin ja hyödyntämällä viime vuosikymmenellä huomattavasti kehittynyttä suurten tietomassojen analysointia on mahdollista kehittää malleja, jotka pystyvät koneoppimisen avulla ennustamaan komplikaatioita ja arvioimaan potilaan ennustetta. Tällaiset mallit pystyvät analysoimaan valtavaa määrää muuttujia ja niiden ajallisia yhteyksiä. Niiden läpinäkyvyys on kuitenkin usein heikko, ja kliinikon on vaikea seurata, miten lopputulokseen on päästy. Kun algoritmeja tarjotaan yhä enemmän ratkaisuiksi kliinisiin ongelmiin, lääkärien tulee ymmärtää mallien rajoitukset ja toisaalta niiden tarjoamat mahdollisuudet.Peer reviewe

Artificiell intelligens i neonatalvård

English summar

Reduction of inflammation by high-dose methylprednisolone does not attenuate oxidative stress in children undergoing bidirectional Glenn procedure with or without aortic arch or pulmonary arterial repair

Objective Corticosteroids attenuate inflammatory reaction in pediatric heart surgery. Inflammation is a source of free oxygen radicals. Children with a cyanotic heart defect are prone to increased radical stress during heart surgery. We hypothesized that high-dose methylprednisolone reduces inflammatory reaction and thereby also oxidative stress in infants with a univentricular heart defect undergoing bidirectional Glenn procedure. Design A double-blind, placebo-controlled, randomized clinical trial. Setting Operation theatre and pediatric intensive care unit of a university hospital. Participants Twenty-nine infants undergoing bidirectional Glenn procedure with or without aortic arch or pulmonary arterial repair. Interventions After anesthesia induction, the patients received intravenously either 30 mg/kg of methylprednisolone (n=15) or the same volume of saline as placebo (n=14). Measurements and Main Results Plasma interleukin-6, interleukin-8 and interleukin-10 (biomarkers of inflammation) as well as 8-hydroxydeoxyguanosine concentrations (a biomarker of oxidative stress) were measured at four different time points: preoperatively, during CPB, after protamine administration, and six hours postoperatively. The study parameters did not differ between the study groups preoperatively. Methylprednisolone reduced the pro-inflammatory cytokines interleukin-6 and interleukin-8 and increased the anti-inflammatory cytokine interleukin-10 postoperatively. Despite reduced inflammation, there were no differences in 8-hydroxydeoxyguanosine between the methylprednisolone and placebo groups. Conclusions Pro-inflammatory reaction and increase in free radical stress were not interrelated during congenital heart surgery in cyanotic infants with a univentricular heart defect undergoing bidirectional Glenn procedure. High-dose methylprednisolone was ineffective in attenuating free radical stress.Peer reviewe

Sikiön synnytyksenaikaisen hapenpuutteen uusi tunnistamiskeino

Siksak-löydös sykekäyrässä on sikiön happivajeen varhainen merkk

Gaussian process classification for prediction of in-hospital mortality among preterm infants

We present a method for predicting preterm infant in-hospital mortality using Bayesian Gaussian process classification. We combined features extracted from sensor measurements, made during the first 72 h of care for 598 Very Low Birth Weight infants of birth weight <1500 g, with standard clinical features calculated on arrival at the Neonatal Intensive Care Unit. Time periods of 12, 18, 24, 36, 48, and 72 h were evaluated. We achieved a classification result with area under the receiver operating characteristic curve of 0.948, which is in excess of the results achieved by using the clinical standard SNAP-II and SNAPPE-II scores. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Intrapartal cardiotocographic patterns and hypoxia-related perinatal outcomes in pregnancies complicated by gestational diabetes mellitus

Aims In previous reports, cardiotocographic (CTG) fetal heart rate (FHR) monitoring has shown only limited benefits in decreasing adverse perinatal outcomes in pregnancies complicated by gestational diabetes mellitus (GDM). The aim of the present study was to evaluate whether an association exists between the recently reported ZigZag pattern (FHR baseline amplitude changes of > 25 bpm with a duration of 2-30 min) and asphyxia-related neonatal outcomes in GDM pregnancies. Methods Intrapartal CTGs were recorded in a one-year cohort of 5150 singleton childbirths. The following CTG changes were evaluated: ZigZag pattern, saltatory pattern, late decelerations, episodes of tachycardia and bradycardia, reduced variability, and uterine tachysystole. The cohort was divided into three groups: women with GDM, women with normal oral glucose tolerance test (OGTT), and women with no OGTT performed. Umbilical artery (UA) blood gases, Apgar scores, neonatal respiratory distress, and neonatal encephalopathy were used as outcome variables. Results GDM was diagnosed in 624 (12.1%), OGTT was normal in 4115 (79.9%), and OGTT was not performed in 411 (8.0%) women. Hypoxia-related ZigZag patterns (OR 1.94, 95% CI 1.64-2.34) and late decelerations (OR 1.65, 95% CI 1.27-2.13) of FHR, as well as a greater risk of fetal asphyxia (UA pH < 7.10 and/or UA BE < -12.0 meq/L and/or Apgar scores < 7 at 5-min) (OR 6.64, 95% CI 1.84-12.03) were observed in those with GDM compared with those without GDM. Conclusions GDM is associated with intrapartal ZigZag pattern and late decelerations, cord blood acidemia and low 5-min Apgar scores at birth indicating increased occurrence of fetal hypoxia in GDM pregnancies.Peer reviewe

Intrapartum zigzag pattern of fetal heart rate is an early sign of fetal hypoxia : A large obstetric retrospective cohort study

Introduction The aim of the present study was to identify possible associations of fetal heart rate (FHR) patterns during the last 2 hours of labor with fetal asphyxia expressed by umbilical artery acidemia at birth and with neonatal complications in a large obstetric cohort. Material and methods Cardiotocographic recordings from 4988 singleton term childbirths over 1 year were evaluated retrospectively and blinded to the pregnancy and neonatal outcomes in a university teaching hospital in Helsinki, Finland. Umbilical artery pH, base excess and pO(2), low Apgar scores at 5 minutes, need for intubation and resuscitation, early neonatal hypoglycemia, and neonatal encephalopathy were used as outcome variables. According to the severity of the neonatal complications at birth, the cohort was divided into three groups: no complications (Group 1), moderate complications (Group 2) and severe complications (Group 3). Results Of the 4988 deliveries, the ZigZag pattern (FHR baseline amplitude changes of >25 bpm with a duration of 2-30 minutes) occurred in 11.7%, late decelerations in 41.0%, bradycardia episodes in 52.9%, reduced variability in 36.7%, tachycardia episodes in 13.9% and uterine tachysystole in 4.6%. No case of saltatory pattern (baseline amplitude changes of >25 bpm with a duration of >30 minutes) was observed. The presence of the ZigZag pattern or late decelerations, or both, was associated with cord blood acidemia (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.3-4.7) and severe neonatal complications (Group 3) (OR 3.3, 95% CI 2.4-4.9). In contrast, no significant associations existed between the other FHR patterns and severe neonatal complications. ZigZag pattern preceded late decelerations in 88.7% of the cases. A normal FHR preceded the ZigZag pattern in 90.4% of the cases, whereas after ZigZag episodes, a normal FHR pattern was observed in only 0.9%. Conclusions ZigZag pattern and late decelerations during the last 2 hours of labor are significantly associated with cord blood acidemia at birth and neonatal complications. The ZigZag pattern precedes late decelerations, and the fact that normal FHR pattern precedes the ZigZag pattern in the majority of the cases suggests that the ZigZag pattern is an early sign of fetal hypoxia, which emphasizes its clinical importance.Peer reviewe