Browsing by Subject "PRETERM"

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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.
  • Zhang, Ge; Bacelis, Jonas; Lengyel, Candice; Teramo, Kari; Hallman, Mikko; Helgeland, Oyvind; Johansson, Stefan; Myhre, Ronny; Sengpiel, Verena; Njolstad, Pal Rasmus; Jacobsson, Bo; Muglia, Louis (2015)
    Background Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach. Methods and Findings We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 x 10(-9)), birth weight (p = 2.19 x 10(-15)), and gestational age (p = 1.51 x 10(-7)). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in similar to 0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects. Conclusions Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring.
  • 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.
  • Airaksinen, Manu; Räsänen, Okko; Ilen, Elina; Häyrinen, Taru; Kivi, Anna; Marchi, Viviana; Gallen, Anastasia; Blom, Sonja; Varhe, Anni; Kaartinen, Nico; Haataja, Leena; Vanhatalo, Sampsa (2020)
    Infants' spontaneous and voluntary movements mirror developmental integrity of brain networks since they require coordinated activation of multiple sites in the central nervous system. Accordingly, early detection of infants with atypical motor development holds promise for recognizing those infants who are at risk for a wide range of neurodevelopmental disorders (e.g., cerebral palsy, autism spectrum disorders). Previously, novel wearable technology has shown promise for offering efficient, scalable and automated methods for movement assessment in adults. Here, we describe the development of an infant wearable, a multi-sensor smart jumpsuit that allows mobile accelerometer and gyroscope data collection during movements. Using this suit, we first recorded play sessions of 22 typically developing infants of approximately 7 months of age. These data were manually annotated for infant posture and movement based on video recordings of the sessions, and using a novel annotation scheme specifically designed to assess the overall movement pattern of infants in the given age group. A machine learning algorithm, based on deep convolutional neural networks (CNNs) was then trained for automatic detection of posture and movement classes using the data and annotations. Our experiments show that the setup can be used for quantitative tracking of infant movement activities with a human equivalent accuracy, i.e., it meets the human inter-rater agreement levels in infant posture and movement classification. We also quantify the ambiguity of human observers in analyzing infant movements, and propose a method for utilizing this uncertainty for performance improvements in training of the automated classifier. Comparison of different sensor configurations also shows that four-limb recording leads to the best performance in posture and movement classification.
  • Khazaei, Mohammad; Raeisi, Khadijeh; Croce, Pierpaolo; Tamburro, Gabriella; Tokariev, Anton; Vanhatalo, Sampsa; Zappasodi, Filippo; Comani, Silvia (2021)
    Neonates spend most of their life sleeping. During sleep, their brain experiences fast changes in its functional organization. Microstate analysis permits to capture the rapid dynamical changes occurring in the functional organization of the brain by representing the changing spatio-temporal features of the electroencephalogram (EEG) as a sequence of short-lasting scalp topographies-the microstates. In this study, we modeled the ongoing neonatal EEG into sequences of a limited number of microstates and investigated whether the extracted microstate features are altered in REM and NREM sleep (usually known as active and quiet sleep states-AS and QS-in the newborn) and depend on the EEG frequency band. 19-channel EEG recordings from 60 full-term healthy infants were analyzed using a modified version of the k-means clustering algorithm. The results show that similar to 70% of the variance in the datasets can be described using 7 dominant microstate templates. The mean duration and mean occurrence of the dominant microstates were significantly different in the two sleep states. Microstate syntax analysis demonstrated that the microstate sequences characterizing AS and QS had specific non-casual structures that differed in the two sleep states. Microstate analysis of the neonatal EEG in specific frequency bands showed a clear dependence of the explained variance on frequency. Overall, our findings demonstrate that (1) the spatio-temporal dynamics of the neonatal EEG can be described by non-casual sequences of a limited number of microstate templates; (2) the brain dynamics described by these microstate templates depends on frequency; (3) the features of the microstate sequences can well differentiate the physiological conditions characterizing AS and QS.
  • Stolt, Suvi; Lind, Annika; Matomäki, Jaakko; Haataja, Leena; Lapinleimu, Helena; Lehtonen, Liisa (2016)
  • Stolt, Suvi; Korja, Riikka; Matomaki, Jaakko; Lapinleimu, Helena; Haataja, Leena; Lehtonen, Liisa (2014)
    Background: It is not clearly understood how the quality of early mother-child interaction influences language development in very-low-birth-weight children (VLBW). Aims: We aim to analyze associations between early language and the quality of mother-child interaction, and, the predictive value of the features of early mother-child interaction on language development at 24 months of corrected age in VLBW children. Study design: A longitudinal prospective follow-up study design was used. Methods: The participants were 28 VLBW children and 34 full-term controls. Language development was measured using different methods at 6, 12 and at 24 months of age. The quality of mother-child interaction was assessed using PC-ERA method at 6 and at 12 months of age. Results: Associations between the features of early interaction and language development were different in the groups of VLBW and full-term children. There were no significant correlations between the features of mother-child interaction and language skills when measured at the same age in the VLBW group. Significant longitudinal correlations were detected in the VLBW group especially if the quality of early interactions was measured at six months and language skills at 2 years of age. However, when the predictive value of the features of early interactions for later poor language performance was analyzed separately, the features of early interaction predicted language skills in the VLBW group only weakly. Conclusions: The biological factors may influence on the language development more in the VLBW children than in the full-term children. The results also underline the role of maternal and dyadic factors in early interactions. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
  • Nyman, Anna; Munck, Petriina; Koivisto, Mari; Hagelstam, Camilla; Korhonen, Tapio; Lehtonen, Liisa; Haataja, Leena (2019)
    Objective: Executive function (EF) problems of children born at very low birth weight (VLBW; = 70 had clinically significant problems in the Working Memory subscale at school. Although they had clinically significant problems at home in the Behavioral Regulation Index, the difference disappeared when adjusted for paternal education. Lower gestational age, lower birth weight z-score, surgical necrotizing enterocolitis, low paternal and maternal education, and lower full-scale IQ were identified to be risk factors for higher scores in ecological assessment of EF. Conclusion: VLBW or VLGA children in this cohort exhibit fewer EF problems in ecological assessment of EF compared to previous literature. EF problems of this study population vary by home and school setting and are emphasized in working memory at school. Screening for EF problems in school environment is recommended to target the support.
  • Huhtala, Mikael S.; Tertti, Kristiina; Juhila, Juuso; Sorsa, Timo; Rönnemaa, Tapani (2020)
    Background: Gestational diabetes mellitus (GDM) is characterized by disturbed glucose metabolism and activation of low-grade inflammation. We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes. Methods: This is a secondary analysis of a previous randomized controlled trial comparing metformin (n = 110) and insulin (n = 107) treatment of GDM. Fasting serum samples were collected at the time of diagnosis (baseline, mean 30 gestational weeks [gw]) and at 36 gw. Inflammatory markers serum high-sensitivity CRP (hsCRP), interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and glycoprotein acetylation (GlycA) as well as three IGFBP-1 phosphoisoform concentrations were determined. Results: In the metformin and insulin groups combined, hsCRP decreased (p = 0.01), whereas IL-6 (p = 0.002), GlycA (p <0.0001) and all IGFBP-1 phosphoisoforms (p <0.0001) increased from baseline to 36 gw. GlycA (p = 0.02) and non-phosphorylated IGFBP-1 (p = 0.008) increased more in patients treated with metformin than those treated with insulin. Inflammatory markers did not clearly associate with pregnancy outcomes but non-phosphorylated IGFBP-1 was inversely associated with gestational weight gain. Conclusions: Metformin had beneficial effects on maternal serum IGFBP-1 concentrations compared to insulin, as increased IGFBP-1 related to lower total and late pregnancy maternal weight gain. GlycA increased more during metformin treatment compared to insulin. The significance of this observation needs to be more profoundly examined in further studies. There were no evident clinically relevant relations between inflammatory markers and pregnancy outcome measures.
  • Antinmaa, Jaana; Lapinleimu, Helena; Salonen, Jaakko; Stolt, Suvi; Kaljonen, Anne; Jääskeläinen, Satu (2020)
    Aim: To study whether auditory function measured with brainstem auditory evoked potential and brainstem audiometry recordings in the neonatal period associates with language development 1 year later in preterm infants.Methods: This retrospective study included 155 preterm infants (birthweight ≤1500 g and/or birth ≤32 gestational weeks) born between 2007 and 2012 at the Turku University Hospital. Auditory function was recorded in neonatal period. Information of language development was gathered at the mean corrected age of 1 year by using the Finnish version of the MacArthur Communicative Development Inventory.Results: Slower auditory processing (longer interpeak interval, IPI I-V) in the right ear in the neonatal brainstem auditory evoked potential recording associated with smaller receptive lexicon size at 1 year (P = .043). Infants with longer IPI I-V were more likely to have a deviant (≤17 words) receptive lexicon size (P = .033). The ab-sence of a contralateral response with right ear stimulation increased the risk for deviant lexicon size (P = .049).Conclusion: The results suggest that impaired auditory function in the neonatal pe-riod in preterm infants may lead to a poorer receptive language outcome 1 year later. Auditory pathway function assessment provides information for the identification of preterm children at risk for weak language development.
  • Gunnar, Riikka J.; Kanerva, Kaisa; Salmi, Silja; Häyrinen, Taru; Haataja, Leena; Pakarinen, Mikko P.; Merras-Salmio, Laura (2020)
    Objective: The impact of pediatric intestinal failure (IF) on neurodevelopment beyond infancy has not been systematically studied. Our aim was to evaluate cognitive and motor impairment and to identify risk factors for adverse outcomes among children with IF. Methods: We conducted a cross-sectional single-center study at the Helsinki University Children's Hospital. Patients with IF with >60 days of parental nutrition (PN) dependency aged between 3 and 16 years (n = 40) were invited to participate. The cognitive and motor skills were evaluated using validated tests: Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, Wechsler Intelligence Scale for Children, 4th edition, and Movement Assessment Battery for Children, 2nd edition. Results: All the patients attending the study tests (n = 30, males = 24) were included. Their median age, gestational age, and birth weight was 7.5 (range 3-16) years, 35 (interquartile range [IQR] 28-38) weeks and 2238 (IQR 1040-3288) grams, respectively. Median duration of PN was 13 (IQR 5-37) months and 9 patients were currently on PN. Median intelligence quotient was 78 (IQR 65-91) and 10 (35%) patients had an intelligence quotient under 70 (-2 standard deviation). Significant motor impairment was detected in 10 patients (36%) and milder difficulties in 8 (28%). Adverse cognitive outcome was associated with neonatal short bowel syndrome, number of interventions under general anesthesia, and length of inpatient status, whereas adverse motor outcome was associated with prematurity. Conclusion: Clinically significant cognitive and motor impairments are alarmingly common among neonatal patients with IF. We recommend early neurodevelopmental follow-up for all children with IF.
  • Kiuru, Annika; Ahola, Terhi; Klenberg, Liisa; Tommiska, Viena; Lano, Aulikki; Kleemola, Päivi; Haavisto, Anu; Fellman, Vineta (2019)
  • Eriksson, Johan G.; Salonen, Minna K.; Kajantie, Eero; Osmond, Clive (2018)
    Background: According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, several noncommunicable diseases, including hypertension, type 2 diabetes, and coronary heart disease, have their origins in early life. Chronic kidney disease (CKD) has traditionally been assumed to develop as the result of an interaction between genetic and environmental factors, although more recently, the importance of factors present early in life has been recognized. Study Design: Longitudinal birth cohort study. Setting & Participants: 20,431 people born in 1924 to 1944 in Helsinki, Finland, who were part of the Helsinki Birth Cohort Study were followed up through their life course from birth until death or age 86 years. Predictor: Prenatal growth and socioeconomic factors. Outcomes: Death or hospitalization for CKD. Results: Smaller body size at birth was associated with increased risk for developing CKD. Each standard deviation higher birth weight was associated with an HR for CKD of 0.82 (95% CI, 0.74-0.91; P <0.001). Associations with ponderal index at birth, placental weight, and birth length were also statistically significant (P <0.001, P <0.001, and P = 0.002, respectively), but only among men. Prematurity also predicted increased risk for CKD. Limitations: The study was restricted to people who were born in Helsinki in 1924 to 1944. Conclusions: Smaller body size at birth was associated with increased risk for developing CKD in men. Prematurity was also associated with increased risk for CKD in women. These findings in the Helsinki Birth Cohort Study support the importance of early life factors in the development of CKD.
  • Stolt, Suvi; Klippi, Anu; Launonen, Kaisa; Munck, Petriina; Lehtonen, Liisa; Lapinleimu, Helena; Haataja, Leena; the PIPARI Study Group (2007)
    "This paper focuses on the aspects of the lexicon in 66 prematurely born very-low-birth-weight and 87 full-term Finnish children at 2;0, studied using the Finnish version of the MacArthur Communicative Developmental Inventory. The groups did not differ in vocabulary size. Furthermore, the female advantage in vocabulary size was not seen in preterm children. The overall shapes of the trajectories for the main lexical categories as a function of vocabulary size were highly similar in both groups and followed those described in the literature. However, there were significant differences in the percentage of nouns and grammatical function words between the two groups. The results suggest that prematurity 'cuts off' the female advantage in vocabulary development. Furthermore, it also seems that there are differences between prematurely born and full-term children in the composition of the lexicon at 2;0. The findings support the universal sequence in the development of lexical categories."