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First-trimester nuchal translucency, nasal bones, and trisomy 21 in selected and unselected populations
Maternal and neonatal outcome after failed ventouse delivery: Comparison of forceps versus cesarean section
Placental edge to internal os distance in the late third trimester and mode of delivery in placenta praevia
First-trimester ductus venosus, nasal bones, and Down syndrome in a high-risk population
Evaluation of fetal arrhythmias from simultaneous pulsed wave Doppler in pulmonary artery and vein
The effect of hypoxaemia on fetal cardiac function
Objectives
The objectives were
1. To study the effect of placental embolisation as well as maternal hypoxaemia on fetal left and right ventricular function as reflected by pulsed-wave Doppler-derived myocardial performance index (MPI).
2. To study myocardial systolic and diastolic function of the fetal left and right ventricles using ultrasound speckle tracking technique to measure global strain and strain rate.
3. To examine if fetal administration of Sildenafil can relieve reactive pulmonary vaso-constriction in a hypoxaemic fetus.
4. To assess the effects of Sildenafil on cardiac function.
Methods
We used pregnant sheep on gestational day 115-129/145 (approximately 4/5th of the length of gestation) for the study. Separate sets of experiments were performed for each component of the study described above. Pregnant sheep were operated under general anaesthesia in order to place measurement equipment in the ewe and the fetus. catheters were placed in fetal carotid artery and jugular vein. An ultrasonic transit-time flow probe was placed around the ductus arteriosus to measure ductal blood flow. Electrodes were placed to obtain fetal ECG. A catheter was kept in the amniotic cavity to measure the amniotic fluid pressure. Experiments were performed after a recovery period of 48-72 hours. Baseline measurements of fetal blood gases and acid-base status were performed.
In the first set of the experiments, we studied the effect of both placental embolisation and fetal hypoxaemia (caused by maternal hypo-oxygenation) on fetal global cardiac function using ultrasound. We evaluated global myocardial function with pulse-wave Doppler-based myocardial performance index. Stored fetal myocardial tissue was subjected to hypoxic gene panel using polymerase chain reaction (PCR) to assess expression of hypoxaemic genes.
In the second set of experiments we studied the changes in function of the fetal heart in response to hypoxaemia. An angle independent technique for assessing myocardial function (ultrasound speckle tracking) was used for this purpose. The evaluation of strain and strain rate was performed off-line on stored loops of the ultrasound examinations carried out during the experiments.
In the third set, fetal cardiac systolic function was evaluated using ventricular outputs, global longitudinal strain/strain rate with speckle tracking echocardiography and isovolumic contraction velocities of the ventricular wall at the level of the mitral and tricuspid valves with tissue Doppler. Diastolic function was evaluated using isovolumic relaxation velocities using tissue Doppler and pulsatility index of the ductus venosus with pulsed wave Doppler ultrasound. Pulmonary blood flow was calculated from the ductus arteriosus flow and left ventricular output. Pulsatility index of the right pulmonary artery was measured with pulsed wave Doppler ultrasound. The measurements were obtained at baseline, with hypoxaemia and at recovery. Animals administered saline or Sildenafil after hypoxemia was induced, and the two groups were used for comparison.
Linear mixed model analysis was used to analyse data on repeated measurements taking into account correlation of measurements carried out in an individual fetus at different time-points. Random intercept model was selected.
Results
Placental vascular resistance and umbilical artery PI increased significantly with placental embolization. During hypoxaemia, mean LV MPI increased significantly only in fetuses with an intact placenta, returning to baseline during the recovery phase. Right ventricular MPI was unaffected. Expression of the hypoxaemic genes was no different with or without placental embolisation. Significantly lower expression of genes involved in cardiac contractile function and its regulation were seen in the group with placental embolisation.
Using speckle tracking echocardiography, baseline mean (SD) left and right ventricular global longitudinal strains were -18.7% (3.8) and -14.3% (5.3) respectively (p = 0.003). Hypoxaemia at 30 and 120 minutes led to a significant reduction (less deformation) in the global longitudinal strain of the LV, while the global circumferential and radial strains were not affected by fetal hypoxaemia. During the recovery period, LV global longitudinal strain returned back to baseline level. Right ventricular global longitudinal, circumferential or radial strains did not change significantly.
In the third set of experiments, fetal hypoxaemia did not affect RVCO that remained unchanged in both groups. However, LVCO and combined cardiac output fell significantly in both the groups during hypoxaemia and remained significantly lower in recovery phase than at baseline. In both groups, lung volume blood flow decreased and flow across the ductus arteriosus increased significantly during hypoxaemia phases with no difference between the Sildenafil and control groups. During hypoxaemia phases left but not right ventricular global longitudinal deformation was reduced (p = 0.003) in both groups. Both right and left ventricular and isovolumic relaxation velocity (IVRV) decreased significantly during hypoxaemia phases with no apparent effect of Sildenafil. Fetal hypoxaemia led to pulmonary arterial vasoconstriction, decreased lung volume blood flow, increased shunting through the ductus arteriosus, reduced left ventricular cardiac output and was associated with evidence of cardiac dysfunction on echocardiography.
Conclusions
In near-term sheep fetus, fetal left ventricle is more sensitive to acute hypoxaemia than the right ventricle. LV global longitudinal and circumferential deformations are greater as compared to RV. Acute hypoxaemia leads to LV rather than RV dysfunction as demonstrated by decreased deformation. Direct administration of Sildenafil to hypoxic fetuses did not reverse redistribution of cardiac output or ameliorate hypoxaemia induced cardiac dysfunction
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Syntymää edeltävien tekijöiden vaikutus sikiöaikaisesta kasvuhidastumasta kärsineiden lasten neurologiseen kehitykseen sekä sydän- ja verenkiertoelimistön toimintaan varhaisessa kouluiässä
AbstractFetal growth restriction (FGR) is a major obstetric problem affecting 3–9% of pregnancies. It is associated with increased perinatal mortality and morbidity as well as increased risk for adverse long-term outcome. The mechanisms leading to neurodevelopmental and cardiovascular problems later in life in FGR are still widely unknown.The present study evaluated the impact of fetal growth and fetal circulatory changes typical of placental insufficiency on long-term outcome at early school age. Neurologic evaluations included parental questionnaires, clinical examinations, language and communication skill assessments and magnetic resonance imaging (MRI) of the head, including detailed diffusion tensor imaging of the white matter. Cardiovascular health was assessed by examining heart rate variability and blood pressure. The findings in children born with FGR were compared to the findings of their gestational age-matched appropriately grown peers (AGA). Furthermore, the impact of prenatal fetoplacental hemodynamic findings on long-term outcomes was studied.Clinical evaluations revealed that children born with FGR, who showed abnormal umbilical artery blood flow, fetal venous circulatory changes and abnormal cardiac function prenatally at any gestational age, were at increased risk for poor neurocognitive development at early school age. Furthermore, significant placental insufficiency and blood flow redistribution increased the risk of poor literacy and communication skills compared with children with normal fetal growth.According to MRI scans, children born with FGR had smaller intracranial volumes at early school age than their AGA peers, with no difference in grey and white matter volumes. In addition, they showed changes in white matter microstructure in several areas when compared with AGA children, indicating that poor fetal growth impacts white matter maturation.In the evaluation of cardiovascular health at early school age, children born with FGR and prenatally detected cerebral vasodilatation showed decreased heart rate variability, indicating changes in the function of the autonomic nervous system and increased risk of later cardiovascular morbidity.In conclusion, FGR and fetoplacental circulatory changes due to placental insufficiency impact cardiovascular and neurologic health at early school age. FGR children with prenatal signs of placental insufficiency and cerebral redistribution have an increased risk of later neurodevelopmental and cardiovascular morbidity.Original papersOriginal papers are not included in the electronic version of the dissertation.Korkalainen, N., Räsänen, J., Kaukola, T., Kallankari, H., Hallman, M., & Mäkikallio, K. (2017). Fetal hemodynamics and adverse outcome in primary school-aged children with fetal growth restriction: A prospective longitudinal study. Acta Obstetricia et Gynecologica Scandinavica, 96(1), 69–77. https://doi.org/10.1111/aogs.13052Korkalainen, N., Mäkikallio, T., Räsänen, J., Huikuri, H., & Mäkikallio, K. (2021). Antenatal hemodynamic findings and heart rate variability in early school-age children born with fetal growth restriction. The Journal of Maternal-Fetal & Neonatal Medicine, 34(14), 2267–2273. https://doi.org/10.1080/14767058.2019.1663816Self-archived versionKorkalainen, N., Partanen, L., Räsänen, J., Yliherva, A., & Mäkikallio, K. (2019). Fetal hemodynamics and language skills in primary school-aged children with fetal growth restriction: A longitudinal study. Early Human Development, 134, 34–40. https://doi.org/10.1016/j.earlhumdev.2019.05.019Self-archived versionKorkalainen, N., Ilvesmäki, T., Parkkola, R., Perhomaa, M., & Mäkikallio K. (2021).
Brain volumes and white matter microstructure in 8–10 year old children born with fetal growth restriction. Manuscript submitted for publication.TiivistelmäSikiöaikaista kasvuhidastumaa esiintyy 3–9 % raskauksista. Sikiöaikaiseen kasvuhidastumaan liittyy lisääntynyt riski syntymänjälkeiseen sairastavuuteen ja kuolleisuuteen sekä kohonnut riski myöhemmän neurokognitiivisen kehityksen ongelmiin sekä sydän- ja verisuonisairauksiin. Biologisia tekijöitä, jotka liittyvät pitkäaikaisiin neurologisiin ja sydän- ja verisuonisairauksiin, tunnetaan huonosti.Tässä tutkimuksessa tarkasteltiin sikiöaikaisen kasvuhidastuman ja istukan vajaatoiminnalle ominaisten verenkierron muutosten vaikutusta lasten neurologiseen kehitykseen sekä sydän- ja verenkiertoelimistön terveyteen varhaisessa kouluiässä. Neurologista kehitystä arvioitiin kliinisten tutkimusten, kyselylomakkeiden, puheterapeutin tutkimuksen sekä pään magneettitutkimuksen (MRI) avulla. Lisäksi selvitimme, ovatko sikiöaikaiset verenkierron muutokset yhteydessä sydämen sykevariaation tai verenpaineen poikkeavuuksiin sikiöaikaisesta kasvuhidastumasta kärsineillä lapsilla. 8–10-vuotiaiden sikiöaikaisesta kasvunhidastumasta kärsineiden lasten löydöksiä verrattiin raskauden keston suhteen kaltaistettuihin verrokkeihin, joiden sikiöaikainen kasvu oli normaalia.Tämän tutkimuksen mukaan sikiöaikaiset muutokset napavaltimon ja laskimopuolen verenkierrossa sekä sydämen toiminnassa ovat raskauden kestosta riippumattomia riskitekijöitä neurokognitiivisen kehityksen ongelmille varhaisessa kouluiässä. Lisäksi havaitsimme, että poikkeava napavaltimon verenvirtaus ja verenkierron uudelleenjakautuminen ovat yhteydessä kielellisen kehityksen ongelmiin. MRI-tutkimusten mukaan kasvunhidastumasta kärsineillä lapsilla aivojen kokonaistilavauus oli pienempi kuin verrokeilla varhaisessa kouluiässä, vaikka muutoksia harmaan tai valkean aineen tilavuuksissa ei todettu. Lisäksi sikiöaikaisesta kasvuhidastumasta kärsineillä lapsilla todettiin muutoksia aivojen valkean aineen rakenteessa, viitaten siihen, että sikiöaikaisen kasvun häiriintyminen vaikuttaa valkean aivoaineen kypsymiseen.Sydän- ja verisuonitutkimuksissa todettiin sikiöaikaisen verenkierron uudelleenjakautumisen olevan yhteydessä poikkeavaan sydämen sykevariaatioon heijastaen autonomisen hermoston toimintamuutoksia jo kouluiässä ja alttiutta myöhemmälle sydän- ja verisuonisairastavuudelle.Sikiöaikainen kasvuhidastuma ja erityisesti istukan vajaatoimintaan liittyvät verenkierron muutokset ovat yhteydessä kouluikäisten neurokognitiivsen kehitykseen ja sydän- ja verenkiertoelimistön toiminnan poikkeavuuksiin.OsajulkaisutOsajulkaisut eivät sisälly väitöskirjan elektroniseen versioon.Korkalainen, N., Räsänen, J., Kaukola, T., Kallankari, H., Hallman, M., & Mäkikallio, K. (2017). Fetal hemodynamics and adverse outcome in primary school-aged children with fetal growth restriction: A prospective longitudinal study. Acta Obstetricia et Gynecologica Scandinavica, 96(1), 69–77. https://doi.org/10.1111/aogs.13052Korkalainen, N., Mäkikallio, T., Räsänen, J., Huikuri, H., & Mäkikallio, K. (2021). Antenatal hemodynamic findings and heart rate variability in early school-age children born with fetal growth restriction. The Journal of Maternal-Fetal & Neonatal Medicine, 34(14), 2267–2273. https://doi.org/10.1080/14767058.2019.1663816Rinnakkaistallennettu versioKorkalainen, N., Partanen, L., Räsänen, J., Yliherva, A., & Mäkikallio, K. (2019). Fetal hemodynamics and language skills in primary school-aged children with fetal growth restriction: A longitudinal study. Early Human Development, 134, 34–40. https://doi.org/10.1016/j.earlhumdev.2019.05.019Rinnakkaistallennettu versioKorkalainen, N., Ilvesmäki, T., Parkkola, R., Perhomaa, M., & Mäkikallio K. (2021).
Brain volumes and white matter microstructure in 8–10 year old children born with fetal growth restriction. Manuscript submitted for publication.Academic dissertation to be presented with the assent of the Doctoral Training Committee of Health and Biosciences of the University of Oulu for public defence in Auditorium 4 of Oulu University Hospital, on 14 January 2022, at 12 noonAbstract
Fetal growth restriction (FGR) is a major obstetric problem affecting 3–9% of pregnancies. It is associated with increased perinatal mortality and morbidity as well as increased risk for adverse long-term outcome. The mechanisms leading to neurodevelopmental and cardiovascular problems later in life in FGR are still widely unknown.
The present study evaluated the impact of fetal growth and fetal circulatory changes typical of placental insufficiency on long-term outcome at early school age. Neurologic evaluations included parental questionnaires, clinical examinations, language and communication skill assessments and magnetic resonance imaging (MRI) of the head, including detailed diffusion tensor imaging of the white matter. Cardiovascular health was assessed by examining heart rate variability and blood pressure. The findings in children born with FGR were compared to the findings of their gestational age-matched appropriately grown peers (AGA). Furthermore, the impact of prenatal fetoplacental hemodynamic findings on long-term outcomes was studied.
Clinical evaluations revealed that children born with FGR, who showed abnormal umbilical artery blood flow, fetal venous circulatory changes and abnormal cardiac function prenatally at any gestational age, were at increased risk for poor neurocognitive development at early school age. Furthermore, significant placental insufficiency and blood flow redistribution increased the risk of poor literacy and communication skills compared with children with normal fetal growth.
According to MRI scans, children born with FGR had smaller intracranial volumes at early school age than their AGA peers, with no difference in grey and white matter volumes. In addition, they showed changes in white matter microstructure in several areas when compared with AGA children, indicating that poor fetal growth impacts white matter maturation.
In the evaluation of cardiovascular health at early school age, children born with FGR and prenatally detected cerebral vasodilatation showed decreased heart rate variability, indicating changes in the function of the autonomic nervous system and increased risk of later cardiovascular morbidity.
In conclusion, FGR and fetoplacental circulatory changes due to placental insufficiency impact cardiovascular and neurologic health at early school age. FGR children with prenatal signs of placental insufficiency and cerebral redistribution have an increased risk of later neurodevelopmental and cardiovascular morbidity.Tiivistelmä
Sikiöaikaista kasvuhidastumaa esiintyy 3–9 % raskauksista. Sikiöaikaiseen kasvuhidastumaan liittyy lisääntynyt riski syntymänjälkeiseen sairastavuuteen ja kuolleisuuteen sekä kohonnut riski myöhemmän neurokognitiivisen kehityksen ongelmiin sekä sydän- ja verisuonisairauksiin. Biologisia tekijöitä, jotka liittyvät pitkäaikaisiin neurologisiin ja sydän- ja verisuonisairauksiin, tunnetaan huonosti.
Tässä tutkimuksessa tarkasteltiin sikiöaikaisen kasvuhidastuman ja istukan vajaatoiminnalle ominaisten verenkierron muutosten vaikutusta lasten neurologiseen kehitykseen sekä sydän- ja verenkiertoelimistön terveyteen varhaisessa kouluiässä. Neurologista kehitystä arvioitiin kliinisten tutkimusten, kyselylomakkeiden, puheterapeutin tutkimuksen sekä pään magneettitutkimuksen (MRI) avulla. Lisäksi selvitimme, ovatko sikiöaikaiset verenkierron muutokset yhteydessä sydämen sykevariaation tai verenpaineen poikkeavuuksiin sikiöaikaisesta kasvuhidastumasta kärsineillä lapsilla. 8–10-vuotiaiden sikiöaikaisesta kasvunhidastumasta kärsineiden lasten löydöksiä verrattiin raskauden keston suhteen kaltaistettuihin verrokkeihin, joiden sikiöaikainen kasvu oli normaalia.
Tämän tutkimuksen mukaan sikiöaikaiset muutokset napavaltimon ja laskimopuolen verenkierrossa sekä sydämen toiminnassa ovat raskauden kestosta riippumattomia riskitekijöitä neurokognitiivisen kehityksen ongelmille varhaisessa kouluiässä. Lisäksi havaitsimme, että poikkeava napavaltimon verenvirtaus ja verenkierron uudelleenjakautuminen ovat yhteydessä kielellisen kehityksen ongelmiin. MRI-tutkimusten mukaan kasvunhidastumasta kärsineillä lapsilla aivojen kokonaistilavauus oli pienempi kuin verrokeilla varhaisessa kouluiässä, vaikka muutoksia harmaan tai valkean aineen tilavuuksissa ei todettu. Lisäksi sikiöaikaisesta kasvuhidastumasta kärsineillä lapsilla todettiin muutoksia aivojen valkean aineen rakenteessa, viitaten siihen, että sikiöaikaisen kasvun häiriintyminen vaikuttaa valkean aivoaineen kypsymiseen.
Sydän- ja verisuonitutkimuksissa todettiin sikiöaikaisen verenkierron uudelleenjakautumisen olevan yhteydessä poikkeavaan sydämen sykevariaatioon heijastaen autonomisen hermoston toimintamuutoksia jo kouluiässä ja alttiutta myöhemmälle sydän- ja verisuonisairastavuudelle.
Sikiöaikainen kasvuhidastuma ja erityisesti istukan vajaatoimintaan liittyvät verenkierron muutokset ovat yhteydessä kouluikäisten neurokognitiivsen kehitykseen ja sydän- ja verenkiertoelimistön toiminnan poikkeavuuksiin
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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