Browsing by Subject "INFANTS"

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  • Domanska, Ausra; Flatt, Justin Wayne; Jukonen, Joonas; Geraets, James; Butcher, Sarah Jane (2019)
    Human parechovirus 3 (HPeV3) infection is associated with sepsis characterized by significant immune activation and subsequent tissue damage in neonates. Strategies to limit infection have been unsuccessful due to inadequate molecular diagnostic tools for early detection and the lack of a vaccine or specific antiviral therapy. Toward the latter, we present a 2.8-angstrom-resolution structure of HPeV3 in complex with fragments from a neutralizing human monoclonal antibody, AT12-015, using cryo-electron microscopy (cryo-EM) and image reconstruction. Modeling revealed that the epitope extends across neighboring asymmetric units with contributions from capsid proteins VP0, VP1, and VP3. Antibody decoration was found to block binding of HPeV3 to cultured cells. Additionally, at high resolution, it was possible to model a stretch of RNA inside the virion and, from this, identify the key features that drive and stabilize protein-RNA association during assembly. IMPORTANCE Human parechovirus 3 (HPeV3) is receiving increasing attention as a prevalent cause of sepsis-like symptoms in neonates, for which, despite the severity of disease, there are no effective treatments available. Structural and molecular insights into virus neutralization are urgently needed, especially as clinical cases are on the rise. Toward this goal, we present the first structure of HPeV3 in complex with fragments from a neutralizing monoclonal antibody. At high resolution, it was possible to precisely define the epitope that, when targeted, prevents virions from binding to cells. Such an atomic-level description is useful for understanding host-pathogen interactions and viral pathogenesis mechanisms and for finding potential cures for infection and disease.
  • Ahlberg, Sara; Grace, Delia; Kiarie, Gideon; Kirino, Yumi; Lindahl, Johanna (2018)
    Aflatoxin M1 (AFM1), a human carcinogen, is found in milk products and may have potentially severe health impacts on milk consumers. We assessed the risk of cancer and stunting as a result of AFM1 consumption in Nairobi, Kenya, using worst case assumptions of toxicity and data from previous studies. Almost all (99.5%) milk was contaminated with AFM1. Cancer risk caused by AFM1 was lower among consumers purchasing from formal markets (0.003 cases per 100,000) than for low-income consumers (0.006 cases per 100,000) purchasing from informal markets. Overall cancer risk (0.004 cases per 100,000) from AFM1 alone was low. Stunting is multifactorial, but assuming only AFM1 consumption was the determinant, consumption of milk contaminated with AFM1 levels found in this study could contribute to 2.1% of children below three years in middle-income families, and 2.4% in low-income families, being stunted. Overall, 2.7% of children could hypothetically be stunted due to AFM1 exposure from milk. Based on our results AFM1 levels found in milk could contribute to an average of −0.340 height for age z-score reduction in growth. The exposure to AFM1 from milk is 46 ng/day on average, but children bear higher exposure of 3.5 ng/kg bodyweight (bw)/day compared to adults, at 0.8 ng/kg bw/day. Our paper shows that concern over aflatoxins in milk in Nairobi is disproportionate if only risk of cancer is considered, but that the effect on stunting children might be much more significant from a public health perspective; however, there is still insufficient data on the health effects of AFM1.
  • Raaska, Hanna; Elovainio, Marko; Sinkkonen, Jari; Stolt, Suvi; Jalonen, Iina; Matomaki, Jaakko; Makipaa, Sanna; Lapinleimu, Helena (2013)
  • Kalliola, Satu; Malmberg, L. Pekka; Malmstrom, Kristiina; Pelkonen, Anna S.; Mäkelä, Mika J. (2019)
    Background: Recurrent wheezing in early life is transient in most children. The significance of airway hyper-responsiveness (AHR) in persistence of respiratory symptoms from infancy to early childhood is controversial. Objective: We evaluated whether AHR in wheezy infants predicts doctor-diagnosed asthma (DDA) or AHR at the age of 6 years. Methods: Sixty-one wheezy infants (age 6-24 months) were followed up to the median age of 6 years. Lung function and AHR with methacholine challenge test were assessed at infancy and 6 years. The exercise challenge test was performed at the age of 6 years. Atopy was assessed with skin prick tests. Results: At 6 years, 21 (34%) of the children had DDA. Children with DDA had higher logarithmic transformed dose-response slope (LOGDRS) to methacholine in infancy than children without DDA (0.047 vs 0.025; P = .033). Furthermore, AHR to methacholine in infancy and at 6 years were associated with each other (r = 0.324, P = .011). Children with exercise-induced bronchoconstriction (EIB) at 6 years were more reactive to methacholine in infancy than those without EIB (P = .019). Conclusion: Increased AHR in symptomatic infants was associated with increased AHR, DDA, and EIB at median the age of 6 years, suggesting early establishment of AHR. (C) 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
  • Joensuu, Eveliina; Munck, Petriina; Setänen, Sirkku; Lipsanen, Jari; Huhtala, Mira; Lapinleimu, Helena; Stolt, Suvi K. J. (2021)
    Preterm children (born
  • 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.
  • Bonamy, Anna-Karin Edstedt; Mohlkert, Lilly-Ann; Hallberg, Jenny; Liuba, Petru; Fellman, Vineta; Domellof, Magnus; Norman, Mikael (2017)
    Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (<27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.
  • Remzső, Gábor; Németh, János; Varga, Viktória; Kovács, Viktória; Tóth-Szűki, Valéria; Kaila, Kai; Voipio, Juha; Domoki, Ferenc (2020)
    Brain interstitial pH (pHbrain) alterations play an important role in the mechanisms of neuronal injury in neonatal hypoxic-ischemic encephalopathy (HIE) induced by perinatal asphyxia. The newborn pig is an established large animal model to study HIE, however, only limited information on pHbrain alterations is available in this species and it is restricted to experimental perinatal asphyxia (PA) and the immediate reventilation. Therefore, we sought to determine pHbrain over the first 24h of HIE development in piglets. Anaesthetized, ventilated newborn pigs (n = 16) were instrumented to control major physiological parameters. pHbrain was determined in the parietal cortex using a pH-selective microelectrode. PA was induced by ventilation with a gas mixture containing 6%O2-20%CO2 for 20 min, followed by reventilation with air for 24h, then the brains were processed for histopathology assessment. The core temperature was maintained unchanged during PA (38.4±0.1 vs 38.3±0.1°C, at baseline versus the end of PA, respectively; mean±SEM). In the arterial blood, PA resulted in severe hypoxia (PaO2: 65±4 vs 23±1*mmHg, *p
  • Eshriqui, Ilana; Viljakainen, Heli T.; Ferreira, Sandra; Raju, Sajan C.; Weiderpass, Elisabete; Figueiredo, Rejane A. O. (2020)
    Background Breastfeeding contributes to gastrointestinal microbiota colonization in early life, but its long-term impact is inconclusive. We aimed to evaluate whether the type of feeding during the first six months of life was associated with oral microbiota in adolescence. Methods This is a cross-sectional sub-study using baseline information of 423 adolescents from the Finnish Health in Teens (Fin-HIT) cohort. Type of feeding was recalled by parents and dichotomized as (i) No infant formula; (ii) Infant formula (breastmilk + formula or only formula). Saliva microbiota was analysed using 16S rRNA (V3-V4) sequencing. Alpha diversity and beta diversity were compared between feeding type groups using ANCOVA and PERMANOVA, respectively. Differential bacteria abundance was tested using appropriate general linear models. Results Mean age and body mass index were 11.7 years and 18.0 kg/m(2), respectively. The No formula group contained 41% of the participants. Firmicutes (51.0%), Bacteroidetes (19.1%), and Proteobacteria (16.3%) were the most abundant phyla among all participants. Alpha and beta diversity indices did not differ between the two feeding groups. Three Operational Taxonomic Units (OTUs) belonging to Eubacteria and Veillonella genera (phylum Firmicutes) were more abundant in the No formula than in the Infant formula group (log2fold changes/ p - values - 0.920/ <0.001, - 0.328/ 0.001, - 0.577/ 0.004). Conclusion Differences exist in abundances of some OTUs in adolescence according to feeding type during the first six months of life, but our findings do not support diversity and overall oral microbiota composition in adolescents being affected by early feeding type.
  • Parviainen, Tiina; Helenius, Päivi; Salmelin, Riitta (2019)
    Auditory cortex in each hemisphere shows preference to sounds from the opposite hemifield in the auditory space. Besides this contralateral dominance, the auditory cortex shows functional and structural lateralization, presumably influencing the features of subsequent auditory processing. Children have been shown to differ from adults in the hemispheric balance of activation in higher-order auditory based tasks. We studied, first, whether the contralateral dominance can be detected in 7- to 8-year-old children and, second, whether the response properties of auditory cortex in children differ between hemispheres. Magnetoencephalography (MEG) responses to simple tones revealed adult-like contralateral preference that was, however, extended in time in children. Moreover, we found stronger emphasis towards mature response properties in the right than left hemisphere, pointing to faster maturation of the right-hemisphere auditory cortex. The activation strength of the child-typical prolonged response was significantly decreased with age, within the narrow age-range of the studied child population. Our results demonstrate that although the spatial sensitivity to the opposite hemifield has emerged by 7 years of age, the population-level neurophysiological response shows salient immature features, manifested particularly in the left hemisphere. The observed functional differences between hemispheres may influence higher-level processing stages, for example, in language function.
  • Männistö, Jonna M. E.; Maria, Maleeha; Raivo, Joose; Kuulasmaa, Teemu; Otonkoski, Timo; Huopio, Hanna; Laakso, Markku (2020)
    Context: Major advances have been made in the genetics and classification of congenital hyperinsulinism (CHI). Objective: To examine the genetics and clinical characteristics of patients with persistent and transient CHI. Design: A cross-sectional study with the register data and targeted sequencing of 104 genes affecting glucose metabolism. Patients: Genetic and phenotypic data were collected from 153 patients with persistent (n = 95) and transient (n = 58) CHI diagnosed between 1972 and 2015. Of these, 86 patients with persistent and 58 with transient CHI participated in the analysis of the selected 104 genes affecting glucose metabolism, including 10 CHI-associated genes, and 9 patients with persistent CHI were included because of their previously confirmed genetic diagnosis. Main outcome measures: Targeted next-generation sequencing results and genotype-phenotype associations. Results: Five novel and 21 previously reported pathogenic or likely pathogenic variants in ABCC8, KCNJ11, GLUD1, GCK, HNF4A, and SLC16A1 genes were found in 68% (n = 65) and 0% of the patients with persistent and transient CHI, respectively. K-ATP channel mutations explained 82% of the mutation positive cases. Conclusions: The genetic variants found in this nationwide CHI cohort are in agreement with previous studies, mutations in the KATP channel genes being the major causes of the disease. Pathogenic CHI-associated variants were not identified in patients who were both diazoxide responsive and able to discontinue medication within the first 4 months. Therefore, our results support the notion that genetic testing should be focused on patients with inadequate response or prolonged need for medication.
  • Turunen, Katri; Antikainen, Jenni; Lääveri, Tinja; Kirveskari, Juha; Svennerholm, Ann-Mari; Kantele, Anu (2020)
    Background: Enterotoxigenic Escherichia coli (ETEC) is a major pathogen causing travellers' diarrhoea (TD) among visitors to low- and middle-income countries (LMIC). Scant data are available on rates of travel-acquired ETEC producing heat-labile (LT) and/or heat-stable (ST) toxin or its subtypes, STh (human) and STp (porcine) in various geographic regions, and on clinical pictures associated with each toxin. Methods: Using qPCR, we analysed LT, STh, and STp in stools positive for ETEC in a prospective study among 103 Finnish travellers visiting LMIC. They filled in questionnaires and provided stool samples before and after travel. We scrutinized geographic distribution of LT, STh, and STp ETEC findings, and association between these different ETEC subtypes and moderate/severe TD. Results: Among the 103 stool samples positive for ETEC toxins, the rate for LT was 76%, for STh 26%, and STp 41%. The rate for LT-only was 44%, for 5Th-only 6%, STp-only 16%, LT + STh 10%, LT + STp 15%, STh + STp 3%, and LT + STh + STp 8%. Findings varied by destination; the rates of LT, STh, and STp were 79%, 21%, and 57%, respectively, in Southern Asia (n = 14); 85%, 10%, and 20% in South-eastern Asia (n = 20); 84%, 13%, and 29% in Eastern Africa (n = 31); and 56%, 50%, and 63% in Western Africa (n = 32), respectively. Of travellers positive for LT, STh, and STp, 83%, 100%, and 88%, encountered TD; 35%, 55%, and 41% reported moderate/severe TD. STh was associated with moderate/severe TD. Conclusions: Toxin findings varied by destination; multiple toxins were commonly detected. Moderate/severe TD was reported most frequently by subjects with STh-ETEC.
  • Grahn, Petra; Pöyhiä, Tiina; Sommarhem, Antti; Nietosvaara, Yrjänä (2019)
    Background and purpose - Patient selection for nerve surgery in brachial plexus birth injury (BPBI) is difficult. Decision to operate is mostly based on clinical findings. We assessed whether MRI improves patient selection. Patients and methods - 157 BPBI patients were enrolled for a prospective study during 2007-2015. BPBI was classified at birth as global plexus injury (GP) or upper plexus injury (UP). The global plexus injury was subdivided into flail upper extremity (FUE) and complete plexus involvement (CP). Patients were seen at set intervals. MRI was scheduled for patients that had either GP at 1 month of age or UP with no antigravity biceps function by 3 months of age. Type (total or partial avulsion, thinned root), number and location of root injuries and pseudomeningoceles (PMC) were registered. Position of humeral head (normal, subluxated, dislocated) and glenoid shape (normal, posteriorly rounded, pseudoglenoid) were recorded. Outcome was assessed at median 4.5 years (1.6-8.6) of age. Results - Cervical MRI was performed on 34/157 patients at median 3.9 months (0.3-14). Total root avulsions (n = 1-3) were detected on MRI in 12 patients (8 FUE, 4 CP). Reconstructive surgery was performed on 10/12 with total avulsions on MRI, and on all 10 with FUE at birth. Sensitivity and specificity of MRI in detecting total root avulsions was 0.88 and 1 respectively. Posterior shoulder subluxation/dislocation was seen in 15/34 patients (3.2-7.7 months of age). Interpretation - Root avulsion(s) on MRI and flail upper extremity at birth are both good indicators for nerve surgery in brachial plexus birth injury. Shoulder pathology develops very early in permanent BPBI.
  • Summanen, Milla; Seikku, Laura; Rahkonen, Petri; Stefanovic, Vedran; Teramo, Kari; Andersson, Sture; Kaila, Kai; Rahkonen, Leena (2017)
    Background: Birth asphyxia, estimated to account for a million neonatal deaths annually, can cause a wide variety of neurodevelopmental impairments. There is a need to develop new, swift methods to identify those neonates who would benefit from neuroprotective treatments such as hypothermia. Objectives: To examine the utility of cord serum copeptin, a stable byproduct of arginine vasopressin release, as a biomarker of birth asphyxia based on a comparison with 2 biomarkers of hypoxia and brain trauma: erythropoietin and S100B. Methods: The study population consisted of 140 singleton, term neonates: 113 controls and 27 with birth asphyxia (2/3 criteria met: umbilical artery pH
  • Kolho, Kaija-Leena; Alfthan, Henrik (2020)
    Objectives Fecal calprotectin is a valued surrogate marker for intestinal inflammation. It has been argued that calprotectin levels are higher in early age than in later life hampering the use of calprotectin in young children. Subjects and methods To study age-related variation, we used data from our laboratory information system on consecutive, unselected fecal calprotectin measurements from 2014 to 2017 in all children aged 0 to 18 years. From each individual, the first measurement was included and repeated measurements were excluded. Fecal calprotectin was quantitated in the major clinical laboratory in southern Finland, HUSLAB with an ELISA kit from Calpro AS (Calpro/Calprolab, Oslo, Norway). Currently, the assay is performed on two automatic pipetting analysers (Dynex DS2, Chantilly, USA) according to the instructions of the manufacturer. Results There were altogether 11,255 fecal calprotectin results from as many children. The median level of fecal calprotectin was 51 mg/kg in infants <1 year of age (95(th)percentile 648 mg/kg;n = 239). This was 3-4-fold higher when compared to yearly age groups from 1 to 10 years (total number of children included 5,691). Across yearly age groups from 11 to 18, the median values varied from 11 to 19 mg/kg (total number of included children 5,325). The proportion of samples above the routine cut-off for an elevated concentration >100 mg/kg increased with increasing age. Conclusions Fecal calprotectin values in children beyond the first year of life are in general low and comparable in children and adolescents.
  • Vainio, Lari; Tiainen, Mikko; Tiippana, Kaisa; Vainio, Martti (2019)
    It has been shown recently that when participants are required to pronounce a vowel at the same time with the hand movement, the vocal and manual responses are facilitated when a front vowel is produced with forward-directed hand movements and a back vowel is produced with backward-directed hand movements. This finding suggests a coupling between spatial programing of articulatory tongue movements and hand movements. The present study revealed that the same effect can be also observed in relation to directional leg movements. The study suggests that the effect operates within the common directional processes of movement planning including at least tongue, hand and leg movements, and these processes might contribute sound-to-meaning mappings to the semantic concepts of 'forward' and 'backward'.
  • Vainio, Lari (2019)
    Mounting evidence shows interaction between manipulative hand movements and movements of tongue, lips and mouth in a vocal and non-vocal context. The current article reviews this evidence and discusses its contribution to perspectives of development and evolution of speech. In particular, the article aims to present novel insight on how processes controlling the two primary grasp components of manipulative hand movements, the precision and power grip, might be systematically connected to motor processes involved in producing certain articulatory gestures. This view assumes that due to these motor overlaps between grasping and articulation, development of these grip types in infancy can facilitate development of specific articulatory gestures. In addition, the hand-mouth connections might have even boosted the evolution of some articulatory gestures. This account also proposes that some semantic sound-symbolic pairings between a speech sound and a referent concept might be partially based on these hand-mouth interactions.
  • Torppa, Ritva; Faulkner, Andrew; Kujala, Teija; Huotilainen, Minna; Lipsanen, Jari (2018)
    THE PERCEPTION OF SPEECH IN NOISE IS challenging for children with cochlear implants (CIs). Singing and musical instrument playing have been associated with improved auditory skills in normal-hearing (NH) children. Therefore, we assessed how children with CIs who sing informally develop in the perception of speech in noise compared to those who do not. We also sought evidence of links of speech perception in noise with MMN and P3a brain responses to musical sounds and studied effects of age and changes over a 14-17 month time period in the speech-in-noise performance of children with CIs. Compared to the NH group, the entire CI group was less tolerant of noise in speech perception, but both groups improved similarly. The CI singing group showed better speech-in-noise perception than the CI non-singing group. The perception of speech in noise in children with CIs was associated with the amplitude of MMN to a change of sound from piano to cymbal, and in the CI singing group only, with earlier P3a for changes in timbre. While our results cannot address causality, they suggest that singing and musical instrument playing may have a potential to enhance the perception of speech in noise in children with CIs.
  • Kallankari, Hanna; Saunavaara, Virva; Parkkola, Riitta; Haataja, Leena; Hallman, Mikko; Kaukola, Tuula (2021)
    Background Very preterm birth can disturb brain maturation and subject these high-risk children to neurocognitive difficulties later. Objective The aim of the study was to evaluate the impact of prematurity on microstructure of frontostriatal tracts in children with no severe neurologic impairment, and to study whether the diffusion tensor imaging metrics of frontostriatal tracts correlate to executive functioning. Materials and methods The prospective cohort study comprised 54 very preterm children (mean gestational age 28.8 weeks) and 20 age- and gender-matched term children. None of the children had severe neurologic impairment. The children underwent diffusion tensor imaging and neuropsychological assessments at a mean age of 9 years. We measured quantitative diffusion tensor imaging metrics of frontostriatal tracts using probabilistic tractography. We also administered five subtests from the Developmental Neuropsychological Assessment, Second Edition, to evaluate executive functioning. Results Very preterm children had significantly higher fractional anisotropy and axial diffusivity values (P
  • the PIPARI Study Group; Lahti, Katri; Saunavaara, Virva; Munck, Petriina; Uusitalo, Karoliina; Koivisto, Mari; Parkkola, Riitta; Haataja, Leena (2020)
    Abstract Aim Very preterm children born less than 32 weeks of gestation are at risk for motor difficulties such as cerebral palsy and developmental coordination disorder. This study explores the association between diffusion tensor imaging metrics at term and motor outcomes at 11 years of age. Methods A cohort of 37 very preterm infants (mean gestational age 29 4/7, SD 2 0/7) born in 2004-2006 in Turku University Hospital underwent diffusion tensor imaging at term. A region-of-interest analysis of fractional anisotropy and mean diffusivity was performed. Motor outcomes at 11 years of age were measured with the Movement Assessment Battery for Children ? Second Edition. Results The diffusion metrics of the corpus callosum (genu p=0.005, splenium p=0.049), the left corona radiata (p=0.035) and the right optic radiation (p=0.017) were related to later motor performance. Mean diffusivity decreased and fractional anisotropy increased in proportion to the improving performance. Conclusion The diffusion metrics of the genu and splenium of the corpus callosum, the left corona radiata and the right optic radiation at term were associated with motor skills at 11 years of age. Diffusion tensor imaging should be further studied as a potential tool in recognising children at risk for motor impairment.