Cognitive Development of Very Low Birth Weight Children from Infancy to Pre-school Age

The survival of preterm born infants has increased but the prevalence of long-term morbidities has still remained high. Preterm born children are at an increased risk for various developmental impairments including both severe neurological deficits as well as deficits in cognitive development. According to the literature the developmental outcome perspective differs between countries, centers, and eras. Definitions of preterm infant vary between studies, and the follow-up has been carried out with diverse methods making the comparison less reliable. It is essential to offer parents upto-date information about the outcome of preterm infants born in the same area. A centralized follow-up of children at risk makes it possible to monitor the consequences of changes in the treatment practices of hospitals on developmental outcome. This thesis is part of a larger regional, prospective multidisciplinary follow-up project entitled “Development and Functioning of Very Low Birth Weight Infants from Infancy to School Age” (PIeniPAinoisten RIskilasten käyttäytyminen ja toimintakyky imeväisiästä kouluikään, PIPARI). The thesis consists of four original studies that present data of very low birth weight (VLBW) infants born between 2001 and 2006, who are followed up from the neonatal period until the age of five years. The main outcome measure was cognitive development and secondary outcomes were significant neurological deficits (cerebral palsy, CP, deafness, and blindness). In Study I, the early crying and fussing behavior of preterm infants was studied using parental diaries, and the relation of crying behavior and cognitive and motor development at the age of two years was assessed. In Study II, the developmental outcome (cognitive, CP, deafness, and blindness) at the age of two years was studied in relation to demographic, antenatal, neonatal, and brain imaging data. Development was studied in relationship to a full-term born control group born in the same hospital. In Study III, the stability of cognitive development was studied in VLBW and full-term groups by comparing the outcomes at the ages of two and five years. Finally, in Study IV the precursors of reading skills (phonological processing, rapid automatized naming, and letter knowledge) were assessed for VLBW and full-term children at the age of five years. Pre-reading skills were studied in relation to demographic, antenatal, neonatal, and brain imaging data. The main findings of the thesis were that VLBW infants who fussed or cried more in the infancy were not at greater risk for problems in their cognitive development. However, crying was associated with poorer motor development. The developmental outcome of the present population was better that has been reported earlier and this improvement covered also cognitive development. However, the difference to fullterm born peers was still significant. Major brain pathology and intestinal perforation were independent significant risk factors for adverse outcome, also when several individual risk factors were controlled for. Cognitive development at the age of two years was strongly related with development at the age of five years, stressing the importance of the early assessment, and the possibility for early interventions. Finally, VLBW children had poorer pre-reading skills compared with their full-term born peers, but the IQ was an important mediator even when children with mental retardation were excluded from the analysis. The findings suggest that counseling parents about the developmental perspectives of their preterm infant should be based on data covering the same birth hospital. Neonatal brain imaging data and neonatal morbidity are important predictors for developmental outcome. The findings of the present study stress the importance of both short-term (two years) and long-term (five years) follow-ups for the individual, and for improving the quality of care.

Den talande bokens poetik : en studie med fokus på olika unga vuxnas reception av tre fiktiva texter inlästa på band

The purpose of the research project The poetics of the talking book is to contribute to the knowledge about patterns of understanding in young adults’ reception of fiction, which they listened to through audio books. The problem explored was: How do different groups of listeners receive fictive text presented as a talking book with variations regarding use of voice, engagement and sound effects? The problem formulation rendered four specific research questions: 1. What patterns can be identified in the listeners’ answers regarding story structure and cognitive content in a comparative perspective comprising different reading styles in the taped versions of the text? 2. What patterns of understanding in interpretative reading can be identified in different listeners? 3. Which thoughts do the listeners have about what the talking book should sound like? 4. What affordances for young adults with the functional disability of mild mental retardation can be made visible through guided literature conversations? The theoretical frame of reference was formed by text–reader-oriented literary theory, psychological schema theory, and research regarding voice quality and communication. The project was carried out in two steps. The first phase was to produce the audio books with two variations of reading practice of three short stories with an existential theme in each text. The second step comprised interviewing of 32 young adults (a special group with a reading handicap in form of mild mental retardation, and a reference group with no handicap). The interviews formed as literary conversation were carried out three times during one year. The phenomenological-hermeneutic approach focused on the life worlds of the participants as meaning seeking beings. The analysis was carried out using method triangulation, mainly using phenomenological meaning concentration. The double hermeneutics in use when interpreting the interpretations of the participants revealed a capacity for aesthetic reading of fiction in the special group as well as in the reference group. The aesthetic qualities were found sufficient in all variations of reading by the professional readers of the audio book they listened to. The young adults also could describe how they wanted the audio book to sound: just as if you were reading yourself. A model describing the analytical steps and concepts in use was a result that can serve as an outline of a poetics for the talking book. Unexpected research results were how important the guided literary conversation turned out to be in order to realise the affordances given by the texts regarding exploration of existential themes in the young adults’ life worlds. Thus the result of the research project can be positioned as a piece of emancipatory research stressing the importance of including this group of young adults in the society’s conversation about culture and meaning.

Prenatal and perinatal risk factors for bipolar disorder

Bipolar disorder (BPD) is a severe mental disorder associated with considerable morbidity and mortality. Prenatal insults have been shown to be associated with later development of mental disorders and there is a growing interest in the potential role of prenatal and perinatal risk factors in the development of BPD. The aims of this thesis were to describe the overall study design of the Finnish Prenatal Study of Bipolar Disorders (FIPS-B) and demographic characteristics of the sample. Furthermore, it was aimed to examine the association of parental age, parental age difference, perinatal complications and maternal smoking during pregnancy with BPD. This thesis is based on FIPS-B, a nested case-control study using several nationwide registers. The cases included all people born in Finland between January 1st 1983 and December 31st 1998 and diagnosed with BPD according to the Finnish Hospital Discharge Register (FHDR) before December 31st 2008. Controls for this study were people who were without BPD, schizophrenia or diagnoses related to these disorders, identified from the Population Register Centre (PRC), and matched two-fold to the cases on sex, date of birth (+/- 30 days), and residence in Finland on the first day of diagnosis of the matched case. Conditional logistic regression models were used to examine the association between risk factors and BPD. This study included 1887 BPD cases and 3774 matched controls. The mean age at diagnosis was 19.3 years and females accounted for 68% of the cases. Mothers with the lowest educational level had the highest odds of having BPD in offspring. Being born in Eastern and Southern region of Finland increased the odds of having BPD later in life. A U-shaped distribution of odds ratio was observed between paternal age and BPD in the unadjusted analysis. Maternal age and parental age difference was not associated with BPD. Birth by planned caesarean section was associated with increased odd of BPD. Smoking during pregnancy was not associated with BPD in the adjusted analyses. Region of birth and maternal educational level were associated with BPD. Both young and old father’s age was associated with BPD. Most perinatal complications and maternal smoking during pregnancy were not associated with BPD. The findings of this thesis, considered together with previous literature, suggest that the pre- and perinatal risk factor profile varies among different psychiatric disorders.

Henkilöstöraportointi strategisen henkilöstöjohtamisen tukena - Case Eteva kuntayhtymä

Organisaatiot kohtaavat jatkuvasti uusia ja vaativia haasteita. Organisaatiot tarvit-sevat henkilöstön asiantuntemusta ja osaamista, jotta voisivat menestyä kaiken aikaa kovenevassa kilpailutilanteessa. Henkilöstön osaaminen, tiedot ja taidot on tunnistettu organisaation tärkeimmäksi voimavaraksi. Tämän tutkimuksen tavoit-teena oli selvittää, millaista tietoa henkilöstä organisaatiossa johtamis- ja esimies-työtä tekevät tarvitsevat strategisen henkilöstöjohtamisen tueksi. Tutkimus suoritettiin tapaustutkimuksena kehitysvammapalveluja tuottavassa or-ganisaatiossa. Empiirinen aineisto kerättiin ja analysoitiin määrällisin menetelmin kyselytutkimuksena. Analysoinnissa käytettiin lisäksi sisällön analyysia. Tutki-muskysely kohdennettiin kohdeorganisaatiossa johtamis- ja esimiestyötä tekevil-le. Kohdeorganisaation johtamis- ja esimiestyötä tekevät tarvitsevat strategisen hen-kilöstöjohtamisen tueksi monipuolista laadullista ja määrällistä tietoa henkilöstös-tä ja taloudesta sekä palautetta oman esimiestyön laadusta. Tieto henkilöstön työhyvinvoinnista ja työtyytyväisyydestä koettiin tärkeäksi. Tuotetut tiedot tulisi olla saatavissa yhdestä paikasta. Esimiehet tarvitsevat myös osaamisen vahvistamista tuotetun tiedon tulkintaan ja käsittelyyn.

Evaluation of Mobile Telephone Text Message Reminders for People with Antipsychotic Medication

Nonadherence to treatment is a worldwide problem among people with severe mental disorders. Patient treatment adherence may be supported with simple reminding methods e.g. text message reminders. However, there is limited evidence of its benefits. Intervention evaluation is essential in mHealth research. Therefore, this evaluative study was conducted. This study aimed to evaluate text message reminder use in encouraging patients’treatment adherence among people with antipsychotic medication. The data were collected between September 2011 and December 2013. First, a systematic literature review revealed that text message reminders were widely used in healthcare. However, its impacts were conflicting. Second, a sub-sample (n = 562) analysis showed that patients preferred humorous text message reminders and preferred to receive them in the morning, at the beginning of the week. Age, gender and marital status seemed to have different effects on the preferred amount and timing of the selected reminders. Third, a cross-sectional survey revealed that people with antipsychotic medication (n = 408) expressed overall satisfaction towards the reminder system. Finally, the evaluative design showed that patient recruitment for a randomized controlled trial concerning people with antipsychotic medication was challenging due to low rates of eligible participants. Follow-up drop-out rates varied depending on the data collection method. Participants’ demographic characteristics were associated with the risk of dropping out from the trial. This study suggests that text messages are a potential reminder system in healthcare services among people with antipsychotic medication. More research is needed to gain a comprehensive picture of the impacts and effectiveness of text message reminders.

Fragiili X -oireyhtymän molekyyligenetiikka ja diagnostiikka. Veritäpläpohjaisen fragiili X -testauksen pystyttäminen

Fragiili X (frax) -oireyhtymä on yleisin kehitysvammaisuuden perinnöllinen syy. Oireyhtymä periytyy X-kromosomissa, ja sen aiheuttaa sytosiini-guaniini-guaniini-emäskolmikon (CGG) monistuminen X-kromosomin Fragile X mental retardation 1 (FMR1) -geenin promoottorialueella. FMR1-alleelit voidaan luokitella (CGG)n-toistojen määrän mukaan neljään ryhmään: normaali (5–44), harmaa alue (45¬¬¬–54), epästabiili esimutaatio (55–200) tai täysmutaatio (yli 200). Esimutaatiotapauksissa toistojakso voi laajentua täysmutaatioksi jo yhden sukupolven aikana. Esimutaation kantajilla on havaittu monenlaisia oireita. Esimerkiksi osalla kantajanaisista on munarauhasen toiminnanhäiriöitä ja erityisesti miehillä on riski sairastua neurologiseen rappeumasairauteen. Täysmutaatiotapauksessa FMR1-promoottorialue metyloituu epänormaalisti ja geeni inaktivoituu. Täysmutaatiota kantavilla miehillä on aina frax-oireyhtymä, kun taas naisilla toisen terveen X-kromosomin suojavaikutus yleensä lieventää oireita sekä täys- että esimutaatiotapauksissa. Oireyhtymän yleisyyden, laajan oirekirjon ja lääkekehityksen edistymisen takia kiinnostus vastasyntyneiden ja kantajien seulontaa kohtaan on kasvanut. Tutkielman kokeellisessa osassa tavoitteena oli pystyttää veritäpläpohjainen automatisoitu DNA-eristysmenetelmä, joka soveltuu frax-oireyhtymän ja sen kantajien testaukseen PerkinElmerin FragilEaseTM-PCR-määrityksen kanssa. Kokonaisuudessaan testaus koostui DNA-eristyksestä, FragilEaseTM-PCR:stä, PCR-tuotteen puhdistuksesta ja monistustuotteiden havainnoinnista kapillaarigeeli-elektroforeesilla. Jokaista vaihetta optimoitiin veritäplätestaukseen sopivaksi. Frax-testaus todistettiin toimivaksi sekä aikuisten että vastasyntyneiden veritäplillä. Halkaisijaltaan 3,2 mm veritäplistä eristettyjen DNA-näytteiden epäpuhtauksista ja alhaisista pitoisuuksista huolimatta FragilEaseTM-PCR:ssä onnistuttiin monistamaan (CGG)n-alueet pienentämällä eristysnäytteiden reaktiotilavuutta ja nostamalla PCR-syklimäärää. Pisin testattu monistusalue oli 200 toistojaksoa. Lisäksi muokkaamalla DNA-eristysvaihetta ja muuttamalla PCR-tuotteen puhdistusmenetelmää onnistuttiin nostamaan lopullista saantoa. Veritäpläpohjaisen frax-testauksen osoitettiin soveltuvan niin vastasyntyneiden kuin kantajien seulontaan.

Brain imaging studies in severe somatization

Somatization was described 4000 years ago but the pathophysiology of the, phenomenon is unknown. The aim of this investigation was to explore whether central nervous system (CNS) pathology is associated with severe somatization which was operationalized as somatization disorder (SD) and undifferentiated somatoform disorder. The study sample consisted of severely somatizing people who were included into the study after a multi-phase screening procedure in order to exclude psychiatric comorbidities and physical illnesses. Diagnosis of somatization disorder or undifferentiated sofatoform disorder were set according to Diagnostic and Statistical Manual of Mental Disorders 4th ed. (DSM-IV). The first study explored the regional cerebral metabolic rate of glucose (rCMRGlc) in severely somatizing females and found it to be reduced in several regions of the brain compared to healthy controls. The second study observed brain morphology with magnetic resonance imaging (MRI) based on the findings from the first study and showed enlarged caudate nuclei in somatizing women compared to healthy volunteers. The third study investigated temperament factors and brain metabolism, and their association with severe somatization. Low caudate and putamen metabolism, low novelty seeking as well as high harm avoidance were found to be associated with severe somatization in women, reduced caudate metabolism having the strongest association. The last study is a report of man with left-side gradient of multiple symptoms of unknown origin in the body. The examination revealed a hypermetabolic nucleus putamen on the contralateral side. All the main results reported in these four articles are original findings. The results suggest that CNS pathology is involved in the pathophysiology of severe somatization.

Pain symptoms and sleep problems among school-aged children. Long-term prevalence changes, and pain symptoms as predictors of later mental health

Children’s pain symptoms and sleep problems are among the most common health complaints. They distract children from activities, decrease the quality of life, contribute to a significant economic burden, and have shown continuity into adulthood. The main aims of this thesis were to investigate long-term changes in the prevalence of pain symptoms and sleep problems among Finnish school-aged children, and the later mental health of those who in childhood experience pain. Prevalence, co-occurrence, and associated psychosocial factors of pain symptoms and sleep problems were also assessed. In study I, prevalence changes in eight-year-old children’s pain symptoms and sleep problems were investigated in three cross-sectional population-based samples (years 1989: n=1038, 1999: n=1035, and 2005: n=1030). In study II, cross-sectional associations between pain symptoms, sleep problems, and psychosocial factors were assessed among 13-18-year-old adolescents (n=2476). In studies III and IV, associations between pain symptoms at age eight (n=6017), and register-based data on antidepressant use and severe suicidality by age 24, were examined in a nationwide birth cohort. Pain symptoms and sleep problems were common and often co-occurred. A considerable number of children’s pain symptoms remained unrecognized by the parents. The prevalence of pain symptoms, sleep problems, and multiple concurrent symptoms approximately doubled from 1989 to 2005. Psychiatric difficulties or demographic factors did not explain the increase. Psychosocial factors that were associated with pain, sleep problems, and a higher number of symptoms, were female sex, psychological difficulties, emotional symptoms, smoking, victimization, and feeling not cared about by teachers. In longitudinal analyses, the child’s own report of headache, and to a smaller degree the parental report of the child’s abdominal pain predicted later antidepressant use. Parental report of the child’s abdominal pain predicted severe suicidality among males. If one of the symptoms is present, health care professionals should inquire about other symptoms as well. Questions should be directed to the children, not only to their parents. Inquiring about psychiatric difficulties, substance use, victimization, and relations with teachers should be included as a part of the assessment. Further studies are needed to clarify the reasons that underlie the increased prevalence rates, and the factors that may increase or decrease the risk for later mental health problems among pain-suffering children.