711 research outputs found
Genomic insights into the Ixodes scapularis tick vector of Lyme disease
No full textCitation: Gulia-Nuss, M., Nuss, A. B., Meyer, J. M., Sonenshine, D. E., Roe, R. M., Waterhouse, R. M., . . . Hill, C. A. (2016). Genomic insights into the Ixodes scapularis tick vector of Lyme disease. Nature Communications, 7, 13. doi:10.1038/ncomms10507Additional Authors: Koren, S.;Hostetler, J. B.;Thiagarajan, M.;Joardar, V. S.;Hannick, L. I.;Bidwell, S.;Hammond, M. P.;Young, S.;Zeng, Q. D.;Abrudan, J. L.;Almeida, F. C.;Ayllon, N.;Bhide, K.;Bissinger, B. W.;Bonzon-Kulichenko, E.;Buckingham, S. D.;Caffrey, D. R.;Caimano, M. J.;Croset, V.;Driscoll, T.;Gilbert, D.;Gillespie, J. J.;Giraldo-Calderon, G. I.;Grabowski, J. M.;Jiang, D.;Khalil, S. M. S.;Kim, D.;Kocan, K. M.;Koci, J.;Kuhn, R. J.;Kurtti, T. J.;Lees, K.;Lang, E. G.;Kennedy, R. C.;Kwon, H.;Perera, R.;Qi, Y. M.;Radolf, J. D.;Sakamoto, J. M.;Sanchez-Gracia, A.;Severo, M. S.;Silverman, N.;Simo, L.;Tojo, M.;Tornador, C.;Van Zee, J. P.;Vazquez, J.;Vieira, F. G.;Villar, M.;Wespiser, A. R.;Yang, Y. L.;Zhu, J. W.;Arensburger, P.;Pietrantonio, P. V.;Barker, S. C.;Shao, R. F.;Zdobnov, E. M.;Hauser, F.;Grimmelikhuijzen, C. J. P.;Park, Y.;Rozas, J.;Benton, R.;Pedra, J. H. F.;Nelson, D. R.;Unger, M. F.;Tubio, J. M. C.;Tu, Z. J.;Robertson, H. M.;Shumway, M.;Sutton, G.;Wortman, J. R.;Lawson, D.;Wikel, S. K.;Nene, V. M.;Fraser, C. M.;Collins, F. H.;Birren, B.;Nelson, K. E.;Caler, E.;Hill, C. A.Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing similar to 57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent
The impact of restricted length of treatment field and anthropometric factors on selection of head and neck cancer patients for treatment on the MR-Linac.
No full textOBJECTIVE: This study investigates the impact of a restricted craniocaudal (CC) field length of <20 cm on the selection of head and neck cancer (HNC) patients who can be treated on the MR-Linac using a single isocentre technique. We also assess the effects of anthropometric factors and the neck position on the CC field length. METHODS: 110 HNC patients who underwent radical primary or adjuvant radiotherapy were retrospectively analysed. We assessed the proportion of treatment fields with a CC length of <20 cm and the effects of gender, height, hyo-sternal neck length (distance from superior surface of hyoid to sternal notch measured on the coronal reconstruction of the planning CT) and neck position on CC length. RESULTS: 95% of HNC patients had a CC field length <20 cm. Female patients showed a significantly shorter median CC length than male patients in both extended (p = 0.0003) and neutral (p = 0.008) neck positions. Neck position influenced the median CC length with neutral neck being significantly shorter than extended neck (p = 0.0119). Patient height and hyo-sternal neck length showed positive correlation with the CC length, with neck length in neutral position having the strongest correlation (r = 0.65, p = 0.0001 and r = 0.63, p < 0.0001, respectively for extended neck; r = 0.55, p = 0.0070 and r = 0.80, p < 0.0001, respectively for neutral neck). A hyo-sternal neck length of <14.6 cm predicted a CC length of <20 cm in neutral neck position. CONCLUSION: The majority of patients with HNC at the Royal Marsden Hospital have anthropometric features compatible with their being treated on the MR-Linac using a single isocentre technique. The absolute CC field size may vary according to primary tumour site, patient factors and neck position. A hyo-sternal neck length cut-off of 14.6 cm in the neutral neck position can be used as a surrogate marker for suitability of treatment on MR-Linac. ADVANCES IN KNOWLEDGE: This paper highlights the potential impact of a restricted CC field in HNC patient selection for the MR-Linac treatment. This is the first report to suggest the use of neck length as a surrogate marker for suitability of treatment on the MR-Linac
Purification and partial characterization of α-D-mannosidase from Erythrina indica seeds
No full text156-160⍺-D-Mannosidase (EC: 3.2.1.24), a glycoprotein with 8.6% carbohydrate was purified (26 fold purification) to homogeneity from Erythrina indica seeds, by gel filtration on Bio-Gel P-100 and affinity chromatography on Con-A CL Seralose. The enzyme had the molecular mass of 124 kDa and 127 kDa by gel filtration and SDS-PAGE, respectively. The optimum pH and temperature for enzyme activity were found to be 4.6 and 50ºC, respectively. The Km value for the enzyme was 2.1 mM for p-nitrophenyl-α-D-mannopyranoside. The enzyme activity was found to depend on the presence of Zn²⁺. Chemical modification studies revealed the involvement of tryptophan, serine and cysteine for enzyme activity
Time‐resolved angiography with stochastic trajectories for dynamic contrast‐enhanced MRI in head and neck cancer: Are pharmacokinetic parameters affected?
No full textPURPOSE: To investigate the effects of different time-resolved angiography with stochastic trajectories (TWIST) k-space undersampling schemes on calculated pharmacokinetic dynamic contrast-enhanced (DCE) vascular parameters. METHODS: A digital perfusion phantom was employed to simulate effects of TWIST on characteristics of signal changes in DCE. Furthermore, DCE-MRI was acquired without undersampling in a group of patients with head and neck squamous cell carcinoma and used to simulate a range of TWIST schemes. Errors were calculated as differences between reference and TWIST-simulated DCE parameters. Parametrical error maps were used to display the averaged results from all tumors. RESULTS: For a relatively wide range of undersampling schemes, errors in pharmacokinetic parameters due to TWIST were under 10% for the volume transfer constant, Ktrans, and total extracellular extravascular space volume, Ve. TWIST induced errors in the total blood plasma volume, Vp, were the largest observed, and these were inversely dependent on the area of the fully sampled k-space. The magnitudes of errors were not correlated with Ktrans, Vp and weakly correlated with Ve. CONCLUSIONS: The authors demonstrated methods to validate and optimize k-space view-sharing techniques for pharmacokinetic DCE studies using a range of clinically relevant spatial and temporal patient derived data. The authors found a range of undersampling patterns for which the TWIST sequence can be reliably used in pharmacokinetic DCE-MRI. The parameter maps created in the study can help to make a decision between temporal and spatial resolution demands and the quality of enhancement curve characterization
Geometric and dosimetric evaluation of the differences between rigid and deformable registration to assess interfraction motion during pelvic radiotherapy
No full textBackground and purpose: Appropriate internal margins are essential to avoid a geographical miss in intensity-modulated radiation therapy (IMRT) for endometrial cancer (EC). This study evaluated interfraction target motion using rigid and non-rigid approximation strategies and calculated internal margins based on random and systematic errors using traditional rigid margin recipes. Dosimetric impact of target motion was also investigated. Materials and methods: Cone beam CTs (CBCTs) were acquired days 1–4 and then weekly in 17 patients receiving adjuvant IMRT for EC; a total of 169 CBCTs were analysed. Interfraction motion for the clinical target volume vaginal vault and upper vagina (CTVv) was measured using bony landmarks and deformation vector field displacement (DVFD) within a 1 mm internal wall of CTVv. Patient and population systematic and random errors were estimated and margins calculated. Delivered dose to the CTVv and organs at risk was estimated. Results: There was a significant difference in target motion assessment using the different registration strategies (p < 0.05). DVFD up to 30 mm occurred in the anterior/posterior direction, which was not accounted for in PTV margins using rigid margin recipes. Underdosing of CTVv D95% occurred in three patients who had substantial reductions in rectal volume (RV) during treatment. RV relative to the planning CT was moderately correlated with anterior/posterior displacement (r = 0.6) and mean relative RV during treatment was strongly correlated with mean relative RV at CBCT acquired days 1–3 (r = 0.8). Conclusion: Complex and extensive geometric changes occur to the CTVv, which are not accounted for in margin recipes using rigid approximation. Contemporary margin recipes and adaptive treatment planning based on non-rigid approximation are recommended
Online adaptive radiotherapy for head and neck cancers on the MR linear Accelerator: Introducing a novel modified Adapt-to-Shape approach.
No full textINTRODUCTION: The Elekta Unity MR-Linac (MRL) has enabled adaptive radiotherapy (ART) for patients with head and neck cancers (HNC). Adapt-To-Shape-Lite (ATS-Lite) is a novel Adapt-to-Shape strategy that provides ART without requiring daily clinician presence to perform online target and organ at risk (OAR) delineation. In this study we compared the performance of our clinically-delivered ATS-Lite strategy against three Adapt-To-Position (ATP) variants: Adapt Segments (ATP-AS), Optimise Weights (ATP-OW), and Optimise Shapes (ATP-OS). METHODS: Two patients with HNC received radical-dose radiotherapy on the MRL. For each fraction, an ATS-Lite plan was generated online and delivered and additional plans were generated offline for each ATP variant. To assess the clinical acceptability of a plan for every fraction, twenty clinical goals for targets and OARs were assessed for all four plans. RESULTS: 53 fractions were analysed. ATS-Lite passed 99.9% of mandatory dose constraints. ATP-AS and ATP-OW each failed 7.6% of mandatory dose constraints. The Planning Target Volumes for 54 Gy (D95% and D98%) were the most frequently failing dose constraint targets for ATP. ATS-Lite median fraction times for Patient 1 and 2 were 40 mins 9 s (range 28 mins 16 s - 47 mins 20 s) and 32 mins 14 s (range 25 mins 33 s - 44 mins 27 s), respectively. CONCLUSIONS: Our early data show that the novel ATS-Lite strategy produced plans that fulfilled 99.9% of clinical dose constraints in a time frame that is tolerable for patients and comparable to ATP workflows. Therefore, ATS-Lite, which bridges the gap between ATP and full ATS, will be further utilised and developed within our institute and it is a workflow that should be considered for treating patients with HNC on the MRL
The Predictive Value of Early Assessment After 1 Cycle of Induction Chemotherapy with 18F-FDG PET/CT and Diffusion-Weighted MRI for Response to Radical Chemoradiotherapy in Head and Neck Squamous Cell Carcinoma.
No full textUNLABELLED: The objective of this study was to assess the predictive value of early assessment (after 1 cycle of induction chemotherapy [IC]) with 18F-FDG PET/CT and diffusion-weighted (DW) MRI for subsequent response to radical chemoradiotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC). METHODS: Twenty patients with stage III-IVa HNSCC prospectively underwent 18F-FDG PET/CT and DW MRI before and 2 wk after each cycle of IC (first cycle, IC1; second cycle, IC2). Response was assessed 3 mo after completion of chemoradiotherapy with clinical examination, MRI, and 18F-FDG PET/CT. Patients with persistent disease were classed as nonresponders. Changes in functional and molecular imaging parameters after IC1 were compared between responders and nonresponders with the Mann-Whitney U test. The significance threshold was set at a P value of less than 0.05. RESULTS: Responders showed a significantly greater reduction in metabolic tumor volume (P = 0.03) and total lesion glycolysis (P = 0.04) after IC1 than nonresponders. Responders also showed a tendency toward a larger but statistically nonsignificant increase in apparent diffusion coefficient after IC1. There was no significant difference in the changes from baseline between the IC1 and IC2 for all functional and molecular imaging parameters, indicating that most biologic response to IC measured by 18F-FDG PET/CT and DW MRI was observed early after the first cycle of IC. CONCLUSION: Our preliminary data indicate that the 18F-FDG PET/CT-derived metabolic tumor volume or total lesion glycolysis, acquired after IC1, are early predictive biomarkers for ultimate response to subsequent chemoradiotherapy. These early biomarkers enable identification of patients at risk of treatment failure at an early time point, permitting treatment individualization and consideration of alternative strategies such as radiotherapy dose escalation or surgery
Circulating tumour DNA is a potential biomarker for disease progression and response to targeted therapy in advanced thyroid cancer
No full textBACKGROUND: Conventional biomarkers in thyroid cancer are not disease specific and fluctuate in advanced disease, making interpretation difficult. Circulating tumour DNA (ctDNA) has been shown to be a useful biomarker in other solid tumours. This is a multimutational study of ctDNA over multiple timepoints, designed to test the hypothesis that ctDNA is a potential biomarker in patients with advanced thyroid cancer.METHODS: Mutational analysis of archival tumour tissue was performed using NGS with a targeted gene panel. Custom TaqMan assays were designed for plasma ctDNA testing using digital droplet polymerase chain reaction. Concentrations of detected ctDNA were correlated with the conventional biomarker concentration and axial imaging status defined by the Response Evaluation Criteria in Solid Tumours criteria.RESULTS: Tumour tissue from 51 patients was obtained, with the following histologies: 32 differentiated (differentiated thyroid cancer [DTC]), 15 medullary (medullary thyroid cancer [MTC]), three poorly differentiated and one anaplastic. NGS analysis detected variants in 42 (82%) of cases. Plasma was assayed for these patients in 190 samples, and ctDNA was detected in 67% of patients. Earlier detection of disease progression was noted in three patients with MTC. In two cases (PTC and ATC), where conventional biomarkers were not detectable, ctDNA was detected before disease progression. Changes in ctDNA concentration occurred earlier than conventional markers in response to disease progression in multiple patients with DTC receiving targeted therapies.CONCLUSION: The majority of patients with advanced thyroid cancer had detectable ctDNA. ctDNA measurement may offer superiority over conventional markers in several scenarios: earlier detection of progression in MTC; as an alternative biomarker when conventional markers are not available; more rapid assessment of the disease status in response to targeted therapies, thereby potentially allowing prompter discontinuation of futile therapies. These early results support the hypothesis that ctDNA may be a clinically useful biomarker in thyroid cancer.</p
Mossbauer study of the SrTiO<SUB>3</SUB>: Co<SUP>57</SUP> system
No full textThe mossbauer investigation of the SrTiO3:Co57 system has indicated the coexistence of low-spin (dε5) and high-spin (dε3dγ
2) ferric states, in contrast to the EPR studies which have shown that iron enters the SrTiO3 lattice at the Ti4+ site in its high-spin trivalent (dε3dγ2) state. The relative intensities of the low-spin high-spin ferric states could be altered by thermal treatment. In highly reduced samples, high-spin ferric (dε3dγ2) and high-spin ferrous (dε4dγ2) states have been observed with an associated charge-compensating oxygen vacancy. The cubic-tetragonal phase transition at 110°K, caused by the accidental degeneracy of longitudinal acoustic and transverse optical modes, has been detected through the temperature variation of isomer shift of the high-spin ferric state
Syntymää edeltävien tekijöiden vaikutus sikiöaikaisesta kasvuhidastumasta kärsineiden lasten neurologiseen kehitykseen sekä sydän- ja verenkiertoelimistön toimintaan varhaisessa kouluiässä
No full textAbstractFetal 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
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