Browsing by Subject "TERM"

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  • Livson, Sivan; Jarva, Hanna; Kalliala, Ilkka; Lokki, A. Inkeri; Heikkinen-Eloranta, Jenni; Nieminen, Pekka; Meri, Seppo (2021)
    Background Human pregnancy alters profoundly the immune system. The local involvement and mechanisms of activation of the complement system in the cervicovaginal milieu during pregnancy and delivery remain unexplored. Objectives To determine whether normal pregnancy and delivery are associated with local activation of complement or changes in the immunoglobulin profile in the cervix. Study Design This study was designed to assess IgA, IgG, and complement activation in the cervicovaginal area in three groups of patients: i) 49 pregnant women (week 41+3-42+0) not in active labor, ii) 24 women in active labor (38+4-42+2), and iii) a control group of nonpregnant women (n=23) at child-bearing age. We collected mucosal samples from the lateral fornix of the vagina and external cervix during routine visits and delivery. The Western blot technique was used to detect complement C3 and its activation products. For semiquantitative analysis, the bands of the electrophoresed proteins in gels were digitized on a flatbed photo scanner and analyzed. IgA and IgG were analyzed by Western blotting and quantified by ELISA. One-way ANOVA and Tukey's Multiple Comparison tests were used for statistical comparisons. Results A higher abundance but lower activation level of C3 in both the external cervix (P Conclusions Our results reveal an unexpectedly strong activation of the complement system and the presence IgG immunoglobulins in the cervicovaginal area during pregnancy, active labor, and among nonpregnant women. In contrast to the higher amounts of C3 in the cervicovaginal secretions during labor, its activation level was lower. Complement activating IgG was detected in higher concentrations than IgA in the mucosal secretions during pregnancy and labor. Taken together our results imply the presence a locally operating humoral immune system in the cervicovaginal mucosa.
  • Marchi, Viviana; Hakala, Anna; Knight, Andrew; D'Acunto, Federica; Scattoni, Maria Luisa; Guzzetta, Andrea; Vanhatalo, Sampsa (2019)
    Aim: General movement assessment requires substantial expertise for accurate visual interpretation. Our aim was to evaluate an automated pose estimation method, using conventional video records, to see if it could capture infant movements using objective biomarkers. Methods: We selected archived videos from 21 infants aged eight to 17 weeks who had taken part in studies at the IRCCS Fondazione Stella Maris (Italy), from 2011 to 2017. Of these, 14 presented with typical low-risk movements, while seven presented with atypical movements and were later diagnosed with cerebral palsy. Skeleton videos were produced using a computational pose estimation model adapted for infants and these were blindly assessed to see whether they contained the information needed for classification by human experts. Movements of skeletal key points were analysed using kinematic metrics to provide a biomarker to distinguish between groups. Results: The visual assessments of the skeleton videos were very accurate, with Cohen's K of 0.90 when compared with the classification of conventional videos. Quantitative analysis showed that arm movements were more variable in infants with typical movements. Conclusion: It was possible to extract automated estimation of movement patterns from conventional video records and convert them to skeleton footage. This could allow quantitative analysis of existing footage.
  • Sandboge, Samuel; Kuula, Juho; Björkqvist, Johan; Hovi, Petteri; Mäkitie, Outi; Kajantie, Eero (2022)
    Background Children and adults born very low birthweight (VLBW,
  • Montazeri Moghadam, Saeed; Pinchefsky, Elana; Tse, Ilse; Marchi, Viviana; Kohonen, Jukka; Kauppila, Minna; Airaksinen, Manu; Tapani, Karoliina; Nevalainen, Päivi; Hahn, Cecil; W. Y. Tam, Emily; Stevenson, Nathan J.; Vanhatalo, Sampsa (2021)
    Neonatal brain monitoring in the neonatal intensive care units (NICU) requires a continuous review of the spontaneous cortical activity, i.e., the electroencephalograph (EEG) background activity. This needs development of bedside methods for an automated assessment of the EEG background activity. In this paper, we present development of the key components of a neonatal EEG background classifier, starting from the visual background scoring to classifier design, and finally to possible bedside visualization of the classifier results. A dataset with 13,200 5-minute EEG epochs (8–16 channels) from 27 infants with birth asphyxia was used for classifier training after scoring by two independent experts. We tested three classifier designs based on 98 computational features, and their performance was assessed with respect to scoring system, pre- and post-processing of labels and outputs, choice of channels, and visualization in monitor displays. The optimal solution achieved an overall classification accuracy of 97% with a range across subjects of 81–100%. We identified a set of 23 features that make the classifier highly robust to the choice of channels and missing data due to artefact rejection. Our results showed that an automated bedside classifier of EEG background is achievable, and we publish the full classifier algorithm to allow further clinical replication and validation studies.
  • Zamorano, Juan Gallego; Hokkanen, Tatu; Lehikoinen, Aleksi (2018)
    Aims Understanding fluctuations in plant reproductive investment can constitute a key challenge in ecology, conservation and management. Masting events of trees (i.e. the intermittent and synchronous production of abundant seeding material) is an extreme example of such fluctuations. Our objective was to establish the degree of spatial and temporal synchrony in common four masting tree species in boreal Finland and account for potential causal drivers of these patterns. Methods We investigated the spatial intraspecific and temporal interspecific fluctuations in annual seed production of four tree species in Finland, silver birch Betula pendula Roth, downy birch Betula pubescens Ehrh., Norway spruce Picea abies (L.) H.Karst. and rowanberry Sorbus aucuparia L. We also tested to see whether variations in seed production were linked to annual weather conditions. Seeding abundance data were derived from tens of stands per species across large spatial scales within Finland during 1979 to 2014 (for rowanberries only 1986 to 2014). Important Findings All species showed spatial synchrony in seed production at scales up to 1000 km. Annual estimates of seed production were strongly correlated between species. Spring and summer temperatures explained most variation in crop sizes of tree species with 0-to 2-year time lags, whereas rainfall had relatively little influence. Warm weather during flowering (May temperature) in the flowering year (Year t) and 2 years before (t-2) were correlated with seed production. However, high May temperatures during the previous year (t-1) adversely affected seed production. Summer temperatures in Year t-1 was positively correlated with seed production, likely because this parameter enhances the development of flower primordials, but the effect was negative with a time lag of 2 years. The negative feedback in temperature coefficients is also likely due to patterns of resource allocation, as abundant flowering and seed production in these species is thought to reduce the subsequent initiation of potential new flower buds. Since the most important weather variables also showed spatial correlation up to 1000 km, weather parameters likely explain much of the spatial and temporal synchrony in seed production of these four studied tree species.
  • Braun, Oscar Ö.; Nilsson, Johan; Gustafsson, Finn; Dellgren, Göran; Fiane, Arnt E.; Lemström, Karl; Hubbert, Laila; Hellgren, Laila; Lund, Lars H. (2019)
    Objectives: The purpose of this study was to assess complications and mortality and its predictors, with continuous-flow left ventricular assist devices (CF-LVADs) in the Nordic Countries. Design: This was a retrospective, international, multicenter cohort study. Results: Between 1993 and 2013, 442 surgically implanted long-term mechanical assist devices were used among 8 centers in the Nordic countries. Of those, 238 were CF-LVADs (HVAD or HeartMate II) implanted in patients >18 years with complete data. Postoperative complications and survival were compared and Cox proportion hazard regression analysis was used to identify predictors of mortality. The overall Kaplan-Meier survival rate was 75% at 1 year, 69% at 2 years and 63% at 3 years. A planned strategy of destination therapy had poorer survival compared to a strategy of bridge to transplantation or decision (2-year survival of 41% vs. 76%, p <.001). The most common complications were non-driveline infections (excluding sepsis) (44%), driveline infection (27%), need for continuous renal replacement therapy (25%) and right heart failure (24%). In a multivariate model age and left ventricular diastolic dimension was left as independent risk factors for mortality with a hazard ratio of 1.35 (95% confidence interval (CI) [1.01-1.80], p = .046) per 10 years and 0.88 (95% CI [0.72-0.99], p = .044) per 5 mm, respectively. Conclusion: Outcome with CF LVAD in the Nordic countries was comparable to other cohorts. Higher age and destination therapy require particularly stringent selection.
  • Leikos, Susanna; Tokariev, Anton; Koolen, Ninah; Nevalainen, Päivi; Vanhatalo, Sampsa (2020)
    Abstract The conventional assessment of preterm somatosensory functions using averaged cortical responses to electrical stimulation ignores the characteristic components of preterm somatosensory evoked responses (SERs). Our study aimed to systematically evaluate the occurrence and development of SERs after tactile stimulus in preterm infants. We analysed SERs performed during 45 electroencephalograms (EEGs) from 29 infants at the mean post-menstrual age of 30.7 weeks. Altogether 2,087 SERs were identified visually at single trial level from unfiltered signals capturing also their slowest components. We observed salient SERs with a high amplitude slow component at a high success rate after hand (95%) and foot (83%) stimuli. There was a clear developmental change in both the slow wave and the higher frequency components of the SERs. Infants with intraventricular haemorrhage (IVH; eleven infants) had initially normal SERs, but those with bilateral IVH later showed a developmental decrease in the ipsilateral SER occurrence after 30 weeks of post-menstrual age. Our study shows that tactile stimulus applied at bedside elicits salient SERs with a large slow component and an overriding fast oscillation, which are specific to the preterm period. Prior experimental research indicates that such SERs allow studying both subplate and cortical functions. Our present findings further suggest that they might offer a window to the emergence of neurodevelopmental sequalae after major structural brain lesions and, hence, an additional tool for both research and clinical neurophysiological evaluation of infants before term age.
  • Kreivi, Hanna-Riikka; Itäluoma, Tuomas; Bachour, Adel (2020)
    Introduction: The prevalence of obesity is continually increasing worldwide, which increases the incidence of obesity hypoventilation syndrome (OHS) and its consequent mortality. Methods: We reviewed the therapy mode, comorbidity and mortality of all OHS patients treated at our hospital between 2005 and 2016. The control group consisted of randomly selected patients with obstructive sleep apnoea (OSA) treated during the same period. Results: We studied 206 OHS patients and 236 OSA patients. The OHS patients were older (56.3 versus 52.3 years, p Conclusions: The mortality rate in OHS was significantly higher than that in OSA patients even after adjusting for covariates. Ventilation therapy by continuous positive airway pressure or noninvasive ventilation have reduced mortality significantly in all patients.
  • Tefre, Sondre; Lilja-Cyron, Alexander; Arvidsson, Lisa; Bartek, Jiri; Corell, Alba; Forsse, Axel; Glud, Andreas Norgaard; Abu Hamdeh, Sami; Hansen, Frederik Lundgaard; Huotarinen, Antti; Johansson, Conny; Kamarainen, Olli-Pekka; Korhonen, Tommi; Kotkansalo, Anna; Mansoor, Nadia Mauland; Mireles, Eduardo Erasmo Mendoza; Miscov, Rares; Munthe, Sune; Nittby-Redebrandt, Henrietta; Obad, Nina; Pedersen, Lars Kjelsberg; Posti, Jussi; Raj, Rahul; Satopää, Jarno; Stahl, Nils; Tetri, Sami; Tobieson, Lovisa; Juhler, Marianne (2022)
    Introduction Endoscopic third ventriculostomy (ETV) is becoming an increasingly widespread treatment for hydrocephalus, but research is primarily based on paediatric populations. In 2009, Kulkarni et al created the ETV Success score to predict the outcome of ETV in children. The purpose of this study is to create a prognostic model to predict the success of ETV for adult patients with hydrocephalus. The ability to predict who will benefit from an ETV will allow better primary patient selection both for EN and shunting. This would reduce additional second procedures due to primary treatment failure. A success score specific for adults could also be used as a communication tool to provide better information and guidance to patients. Methods and analysis The study will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis reporting guidelines and conducted as a retrospective chart review of all patients >= 18 years of age treated with EN at the participating centres between 1 January 2010 and 31 December 2018. Data collection is conducted locally in a standardised database. Univariate analysis will be used to identify several strong predictors to be included in a multivariate logistic regression model. The model will be validated using K-fold cross validation. Discrimination will be assessed using area under the receiver operating characteristic curve (AUROC) and calibration with calibration belt plots. Ethics and dissemination The study is approved by appropriate ethics or patient safety boards in all participating countries.
  • Korkalainen, Noora; Partanen, Lea; Räsänen, Juha; Yliherva, Anneli; Mäkikallio, Kaarin (2019)
    Aim: Long-term follow-up studies on children born with fetal growth restriction (FGR) have revealed a specific profile of neurocognitive difficulties, including problems with speech, language and literacy skills. We hypothesized that problems with communication skills, including language use and literacy skills of FGR children at primary school age are associated with prenatal circulatory changes. Methods: Ultrasonographic assessment of fetoplacental hemodynamics was performed prenatally in 77 fetuses. After a follow-up period of 8-10 years, assessment of reading and spelling skills using standardized tests and the Children's Communication Questionnaire (CCC-2) was performed to measure different language skills in 37 FGR children and 31 appropriately grown (AGA) controls, matched for gestational age. Results: Increased blood flow resistance in the umbilical artery (UA PI > 2 SD) during fetal life showed odds ratios of 3.5-19.1 for poor literacy and communication skills and need for speech and language therapy. Furthermore, FGR children with prenatal cerebral vasodilatation (cerebroplacental ratio (CPR) <-2 SD) had significantly poorer literacy and communication skills, at primary school age compared to the AGA controls. Abnormal CPR demonstrated odds ratios of 4.2-28.1 for poor literacy and communication skills and need for speech and language therapy. Conclusion: Increased blood flow resistance in the umbilical artery and cerebral vasodilatation are associated with poor communication, language, and literacy skills at early school age in children born with FGR. These findings indicate the need for continuous follow-up of this group and timely targeted support to ensure optimal academic outcomes.
  • Persson, Martina; Opdahl, Signe; Risnes, Kari; Gross, Raz; Kajantie, Eero; Reichenberg, Abraham; Gissler, Mika; Sandin, Sven (2020)
    Introduction The complex etiology of autism spectrum disorder (ASD) is still unresolved. Preterm birth ( Author summaryWhy was this study done? Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent impairments in social communication and restricted and repetitive behaviors. The etiology remains unresolved. Length of gestation, including preterm birth, has been linked to risk of ASD, but reliable estimates of risks for the whole range of gestational ages (GAs) are lacking. The primary objective of this study was to provide a detailed and robust description of ASD risk across the entire range of GA while taking fetal sex and size at birth into account. What did the researchers do and find? This study was based on population-based data from national medical registries in three Nordic countries-Sweden, Finland, and Norway-and included 3,526,174 singletons born 1995 to 2015. Relative risks (RRs) of ASD by GA at birth were estimated with log binominal regression. The RR of ASD increased by each week of GA, pre- as well as postterm, from 40 to 24 weeks of gestation and from 40 to 44 weeks of gestation, independently of sex and birth weight for GA. What do these findings mean? On a population level, the risks of ASD were increased in children born either pre- or postterm, including children born close to week 40. We found that the risk of ASD increased weekly, with each week further away from 40 weeks of gestation.
  • Hukkinen, Maria; Merras-Salmio, Laura; Pakarinen, Mikko P. (2018)
    Treatment results of pediatric intestinal failure have improved markedly during the last decades. With improved survival the attention is turning to other essential outcomes including quality of life and neurodevelopment. So far, relatively few studies with limited number of patients and variable methodology have addressed these issues. Based on these studies using generic health related quality of life tools, children with intestinal failure demonstrate decreased physical health, while PN-dependence is also associated with compromised emotional functioning. Impairments of social functioning are frequently observed among older children and parents. Few recent studies on neurodevelopment imply significant impairments in motor and mental skills among children with intestinal failure despite small sample sizes and limited follow-up times. Development of a disease-specific survey designed for the pediatric intestinal failure population could better reveal the health issues with greatest impact on quality of life. Robust studies with appropriate methodology on neurodevelopment in pediatric intestinal failure with extended follow-up times are urgently needed. Quality of life and neurodevelopment requires greater attention from medical professionals managing children with intestinal failure. (C) 2018 Elsevier Inc. All rights reserved.
  • Berdal, Elias Kjolseth; Wollum, Arnt Erik Karlsen; Hollund, Ingrid Marie Husby; Iversen, Johanne Marie; Kajantie, Eero; Evensen, Kari Anne I. (2022)
    Background Preterm birth with very low birth weight (VLBW, birth weight < 1500 g) is associated with health problems later in life. How VLBW individuals perceive their physical and mental health-related quality of life (HRQoL) is important to understand their putative burden of disease. Previous studies have shown mixed results, and longitudinal studies into adulthood have been requested. This study aimed to investigate differences in HRQoL between preterm VLBW and term born individuals at 32 years of age, and to study changes in HRQoL from 20 to 32 years. Methods In a geographically based longitudinal study, 45 VLBW and 68 term born control participants completed the Short Form 36 Health Survey (SF-36) at 32 years of age. Data from three previous timepoints was also available (20, 23 and 28 years of age). The SF-36 yields eight domain scores as well as a physical and a mental component summary. Between-group differences in these variables were investigated. We also performed subgroup analyses excluding individuals with disabilities, i.e., cerebral palsy and/or low estimated intelligence quotient. Results At 32 years of age, the physical component summary was 5.1 points lower (95% confidence interval (CI): 8.6 to 1.6), and the mental component summary 4.1 points lower (95% CI: 8.4 to - 0.3) in the VLBW group compared with the control group. For both physical and mental component summaries there was an overall decline in HRQoL from 20 to 32 years of age in the VLBW group. When we excluded individuals with disabilities (n = 10), group differences in domain scores at 32 years were reduced, but physical functioning, bodily pain, general health, and role-emotional scores remained lower in the VLBW subgroup without disabilities compared with the control group. Conclusion We found that VLBW individuals reported lower HRQoL than term born controls at 32 years of age, and that HRQoL declined in the VLBW group from 20 to 32 years of age. This was in part, but not exclusively explained by VLBW individuals with disabilities.
  • Mehl, Cathrin Vano; Hollund, Ingrid Marie Husby; Iversen, Johanne Marie; Lydersen, Stian; Mork, Paul Jarle; Kajantie, Eero; Evensen, Kari Anne (2022)
    Background Individuals born small for gestational age (SGA) have an increased risk of several adverse health outcomes, but their health-related quality of life (HRQoL) across young adulthood has yet to be studied. The main aim of this study was to investigate if being born SGA at term is associated with poor HRQoL at 32 years of age. A second aim was to explore longitudinal changes in HRQoL from age 20 to 32 years. Methods In the prospective NTNU Low Birth Weight in a Lifetime Perspective study, 56 participants born SGA and 68 non-SGA control participants completed the Short Form 36 Health Survey (SF-36) at age 32 years to assess HRQoL. The SF-36 was also administrated at age 20 and 28 years. Longitudinal changes in the eight SF-36 domains and the two component summaries from 20 to 32 years were analyzed by linear mixed models. In total, 82 adults born SGA and 98 controls participated at least once and were included in the longitudinal analyses. Results At age 32 years the participants born SGA scored 14.8 (95% CI 4.7 to 25.3) points lower in the SF-36 role-physical domain compared with the control group, i.e. more problems with work or other daily activities due to physical health problems. The longitudinal analyses showed significant group differences from 20 to 32 years in the role-emotional domain, and in the physical and mental component summaries. Among participants born SGA, the physical component summary decreased from age 20 to 28 years (-3.2, 95% CI -5.0 to -1.8), while the mental component summary (6.0, 95% CI 2.9 to 8.6) and role-emotional domain score (19.3, 95% CI 9.9 to 30.3) increased, but there were no further changes from 28 to 32 years. There were no longitudinal changes in the control group from 20 to 32 years. Conclusion Overall, individuals born SGA at term reported similar HRQoL at age 32 years compared with non-SGA controls. Self-perceived mental health improved during young adulthood among individuals born SGA, while self-perceived physical health deteriorated. The latter findings warrant further investigation.
  • Juottonen, Heli; Kieman, Mirkka; Fritze, Hannu; Hamberg, Leena; Laine, Anna M.; Merila, Paivi; Peltoniemi, Krista; Putkinen, Anuliina; Tuittila, Eeva-Stiina (2022)
    Peatlands are carbon dioxide (CO2) sinks that, in parallel, release methane (CH4). The peatland carbon (C) balance depends on the interplay of decomposer and CH4-cycling microbes, vegetation, and environmental conditions. These interactions are susceptible to the changes that occur along a successional gradient from vascular plant-dominated systems to Sphagnum moss-dominated systems. Changes similar to this succession are predicted to occur from climate change. Here, we investigated how microbial and plant communities are interlinked with each other and with ecosystem C cycling along a successional gradient on a boreal land uplift coast. The gradient ranged from shoreline to meadows and fens, and further to bogs. Potential microbial activity (aerobic CO2 production; CH4 production and oxidation) and biomass were greatest in the early successional meadows, although their communities of aerobic decomposers (fungi, actinobacteria), methanogens, and methanotrophs did not differ from the older fens. Instead, the functional microbial communities shifted at the fen-bog transition concurrent with a sudden decrease in C fluxes. The successional patterns of decomposer versus CH4-cycling communities diverged at the bog stage, indicating strong but distinct microbial responses to Sphagnum dominance and acidity. We highlight young meadows as dynamic sites with the greatest microbial potential for C release. These hot spots of C turnover with dense sedge cover may represent a sensitive bottleneck in succession, which is necessary for eventual long-term peat accumulation. The distinctive microbes in bogs could serve as indicators of the C sink function in restoration measures that aim to stabilize the C in the peat.
  • Järvinen, Tommi; Ilonen, Ilkka; Kauppi, Juha; Salo, Jarmo; Räsänen, Jari (2018)
    Background: Nutritional deficits, cachexia, and sarcopenia are extremely common in esophageal cancer. The aim of this article was to assess the effect of loss of skeletal muscle mass during neoadjuvant treatment on the prognosis of esophageal cancer patients. Methods: Esophageal cancer patients (N = 115) undergoing neoadjuvant therapy and surgery between 2010 and 2014 were identified from our surgery database and retrospectively analyzed. Computed tomography imaging of the total cross-sectional muscle tissue measured at the third lumbar level defined the skeletal muscle index, which defined sarcopenia (SMI <52.4 cm2/m2 for men and <38.5 cm2/m2 for women). Images were collected before and after neoadjuvant treatments. Results: Sarcopenia in preoperative imaging was prevalent in 92 patients (80%). Median overall survival was 900 days (interquartile range 334-1447) with no difference between sarcopenic (median = 900) and non-sarcopenic (median = 914) groups (p = 0.872). Complication rates did not differ (26.1% vs 32.6%, p = 0.725). A 2.98% decrease in skeletal muscle index during neoadjuvant treatment correlated with poor 2-year survival (log-rank p = 0.04). Conclusion: Loss of skeletal muscle tissue during neoadjuvant treatment correlates with worse overall survival.
  • Kruit, Heidi; Heikinheimo, Oskari; Ulander, Veli-Matti; Aitokallio-Tallberg, Ansa; Nupponen, Irmeli; Paavonen, Jorma; Rahkonen, Leena (2015)
    Background: Induction of labour is associated with increased risk for caesarean delivery among nulliparous women. The aims of this study were to evaluate the risk factors for caesarean delivery and to investigate the risk of maternal and neonatal infections in nulliparous women undergoing induction of labour by Foley catheter. Methods: This clinical retrospective study of 432 nulliparous women with singleton pregnancy and intact amniotic membranes at or beyond 37 gestational weeks scheduled for induction of labour by Foley catheter was conducted over the course of one year, between January 2012 and January 2013, in Helsinki University Hospital. The main outcome measures were caesarean section rate and maternal and neonatal infections. Univariate and multivariate logistic regressions were used to estimate relative risks by odds ratios with 95 % confidence intervals. Results: The caesarean section rate was 39.1 % (n = 169). In multivariate regression analysis, the factors associated with caesarean section were the need for oxytocin for labour induction [OR 2.9 (95 % CI 1.8-4.5) p <0.001] and early epidural analgesia [OR 9.9 (95 % CI 2.1-47.5), p = 0.004]. The maternal intrapartum infection rate was 6.3 %, and the clinical neonatal infection rate was 2.8 %. In multivariate analysis, gestational diabetes was associated with maternal intrapartum infection [OR 4.3 (95 % CI 1.7-11.0, p = 0.002] and early epidural analgesia with neonatal clinical sepsis [OR 10.5 (95 % CI 1.4-76), p = 0.02]. Conclusions: Oxytocin induction and early epidural analgesia were associated with caesarean delivery. Gestational diabetes and early epidural analgesia were associated with infectious morbidity. Since the first caesarean delivery has a major impact on subsequent pregnancies, optimising labour induction among nulliparous women is important.
  • Kivisto, Julia; Lehto, Soili M.; Halonen, Katja; Georgiadis, Leena; Heinonen, Seppo (2016)
    Background Antenatal depression affects up to 19% of pregnant women. Some of these women are also in need of antidepressant treatment. Nevertheless, the impact of maternal antidepressant treatment and prenatal depression on the course of pregnancy, foetal development and delivery outcomes is not fully understood. Methods We analysed data from 24 818 women who gave birth at Kuopio University Hospital between 2002-2012. Logistic regression analysis was used to estimate associations between the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and the progression of pregnancy, development of the foetus and delivery outcomes. Results Altogether, 369 (1.5%) women used SSRIs. A regression model adjusted for age, overweight, nulliparity, prior termination, miscarriages, smoking, maternal alcohol consumption, chronic illness and polyhydramnion showed that pregnant women exposed to SSRI medication had significantly lower Apgar scores at 1 minute (p <0.0001) and 5 minutes (p <0.0001) and more admissions to the neonatal intensive care unit (p <0.0001) than unexposed pregnant women. In addition, exposed newborns had longer umbilical cords (p <0.0001) than non-exposed newborns. Conclusion In addition to the previously known associates with maternal SSRI exposure, such as lowered Apgar scores, SSRI exposure appeared to be associated with increased umbilical cord length. The observation related to increased umbilical cord length may be explained by an SSRI-induced increase in the movements of the developing foetus.
  • Hähnel, Tom; Baldow, Christoph; Guilhot, Joelle; Guilhot, Francois; Saussele, Susanne; Mustjoki, Satu; Jilg, Stefanie; Jost, Philipp J.; Dulucq, Stephanie; Mahon, Francois-Xavier; Roeder, Ingo; Fassoni, Artur C.; Glauche, Ingmar (2020)
    Recent clinicalfindings in patients with chronic myeloid leukemia (CML) suggest that the risk of molecular recurrence after stopping tyrosine kinase inhibitor (TKI) treatment substantially depends on an individual's leukemia-specific immune response. However, it is still not possible to prospectively identify patients that will remain in treatment-free remission (TFR). Here, we used an ordinary differential equation model for CML, which explicitly includes an antileukemic immunologic effect, and applied it to 21 patients with CML for whom BCR-ABL1/ABL1 time courses had been quantified before and after TKI cessation. Immunologic control was conceptually necessary to explain TFR as observed in about half of the patients. Fitting the model simulations to data, we identified patient-specific parameters and classified patients into three different groups according to their predicted immune system configuration ("immunologic landscapes"). While one class of patients required complete CML eradication to achieve TFR, other patients were able to control residual leukemia levels after treatment cessation. Amongthem were a third class of patients that maintained TFR only if an optimal balance between leukemia abundance and immunologic activation was achieved before treatment cessation. Model simulations further suggested that changes in the BCR-ABL1 dynamics resulting from TKI dose reduction convey information about the patient-specific immune system and allow prediction of outcome after treatment cessation. This inference of individual immunologic configurations based on treatment alterations can also be applied to other cancer types in which the endogenous immune system supports maintenance therapy, long-term disease control, or even cure. Significance: This mathematical modeling approach provides strong evidence that different immunologic configurations in patients with CML determine their response to therapy cessation and that dose reductions can help to prospectively infer different risk groups.
  • Nevalainen, Päivi; Metsäranta, Marjo; Toiviainen-Salo, Sanna; Marchi, Viviana; Mikkonen, Kirsi; Vanhatalo, Sampsa; Lauronen, Leena (2020)
    Purpose: To evaluate the accuracy of hypoxic ischemic encephalopathy (HIE) grade, and neonatal neurophysiological and neuroimaging measures for predicting development of infantile spasms syndrome (IS) or other postneonatal, infantile onset epilepsy after perinatal HIE. Methods: We examined a population-based cohort of 92 consequent infants with moderate-to-severe HIE. The HIE grade and neonatal neuroimaging (MRI) and neurophysiology (EEG and somatosensory evoked potentials, SEPs) findings were compared to the development of IS or other epilepsy within the first year of life. Results: Out of 74 surviving infants with follow-up information, five developed IS and one developed a focal onset epilepsy. They all had recovered from severe HIE. All survivors with inactive neonatal EEG (recorded within the first few postnatal days, n = 4) or the most severe type of brain injury in MRI (n = 3) developed epilepsy (positive predictive value, PPV 100 %). Bilaterally absent SEPs had 100 % sensitivity and 75 % PPV for epilepsy. A combination of absent SEPs and a poor MRI finding (combined deep and cortical gray matter injury) resulted in higher PPV (86 %) without lowering sensitivity (100 %). Follow-up EEGs showed recurrent epileptiform activity already between 1- and 2-months age in those that developed epilepsy, distinguishing them from those surviving without epilepsy. Conclusions: Poor neonatal neuroimaging and neurophysiological findings provide accurate prediction for development of infantile onset epilepsy after HIE. Of the neonates with severe HIE, the ones with severe neonatal MRI and neurophysiological abnormalities need frequent follow-up, including repeated EEGs, for early detection of IS.