| 1. |
- Gardiner, Helena
(författare)
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The Influence of Intrauterine Environment on Cardiovascular Development During Fetal Life
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fetal growth restriction has been linked to later cardiovascular disease, possibly through reduced arterial distensibility in response to a suboptimal intrauterine environment. This thesis sought firstly to examine the relationship between fetal growth and haemodynamics and their effect on later cardiovascular function and secondly to examine the effects of differential volume loading on arterial distensibility in genetically identical monochorionic twins with twin-twin transfusion syndrome (TTTS) and to explore the effect that early treatment has on vascular development. Pulse wave velocity, cardiovascular growth and haemodynamics and the response of heart rate and blood pressure to tilt-testing in infancy were examined in two cohorts of normally grown (N) and growth restricted (GR) fetuses examined serially during fetal life and through the first year of life. Fetal growth restriction was associated with altered vascular behaviour, volume blood flow and increased thickness of cardiac walls, possibly in response to documented increased systemic impedance, but by a year of age no differences were observed. Arterial distensibility was higher in GR during the fetal and neonatal periods but not later in infancy. Heart rate was higher in GR during infancy suggesting increased sympathetic drive and blood pressure showed a trend towards higher values. Abnormal responses to tilt testing were documented in GR individuals who had shown abnormal fetal blood flow Doppler waveforms suggesting a possible influence on later baroreceptor function. Monochorionic twins with TTTS showed discordant arterial distensibility that was not present in monochorionic or dichorionic controls. Early definitive treatment with laser photocoagulation reduced, but did not completely abolish intertwin discordance, suggesting that vasoactive substances produced in response to differential volume loading in TTTS may influence later vascular behaviour despite definitive treatment of the disease process in the second trimester.
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| 2. |
- Gardiner, Helena, et al.
(författare)
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Ventriculo-vascular interaction in the normal development of the fetal circulation
- 2001
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Ingår i: Early Human Development. - 1872-6232. ; 65:2, s. 97-106
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine cardiovascular physiology in the healthy fetus during normal development. DESIGN: Twenty normal fetuses were studied longitudinally from 20 weeks to term. Serial echocardiography was performed, and arterial and venous diameter pulse wave characteristics and aortic pulse wave propagation velocity (PWV) were examined in the thoracic descending aorta (AoD) and inferior caval vein (IVC) using an ultrasonic phase-locked echo-tracking system. Statistical analyses included ANOVA, paired t-test and logistic regression where appropriate. RESULTS: Aortic PWV, maximum incremental and late decremental velocities increased with gestation while the relative pulse amplitude decreased, reflecting falling distal impedance. There was a linear increase in cardiac preload and relative pulse amplitude in the IVC with gestation that correlated significantly with the presence of end-diastolic flow in the pulmonary artery and improvement in right ventricular diastolic function. CONCLUSIONS: Non-invasive concurrent assessment of preload, ventricular function and impedance are possible in the fetus and may prove useful in the longitudinal study of fetal adaptation to pathophysiological changes.
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| 3. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 4. |
- Matsui, Hikoro, et al.
(författare)
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Morphological and physiological predictors of fetal aortic coarctation.
- 2008
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Ingår i: Circulation. - 1524-4539. ; 118:18, s. 1793-801
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prenatal diagnosis of aortic coarctation suffers from high false-negative rates at screening and poor specificity. METHODS AND RESULTS: This retrospective study tested the applicability of published aortic arch and ductal Z scores (measured just before the descending aorta in the 3-vessel and tracheal view) and their ratio on 200 consecutive normal controls at a median of 22+/-0 gestational weeks (range, 15+/-4 to 38+/-4 weeks). Second, this study tested the ability of serial Z scores to distinguish fetuses with coarctation within a cohort with ventricular and/or great arterial disproportion detected at screening or fetal echocardiography. Third, it evaluated the diagnostic significance of associated cardiac lesions, coarctation shelf, and isthmal flow disturbance. We studied 44 fetuses with suspected coarctation at 24+/-0 weeks (range, 17+/-3 to 37+/-4 weeks). Receiver-operating characteristic curves were created. Logistic regression tested the association between z scores, additional cardiac diagnoses, and coarctation. Good separation was found of isthmal Z scores for cases requiring surgery from controls and false-positive cases, and receiver-operating characteristic curves showed an excellent area under the curve for isthmal Z score (0.963) and isthmal-to-ductal ratio (0.969). Serial isthmal Z scores improved to >-2 in suspected cases with normal outcomes; those requiring surveillance or surgery remained <-2. Minor lesions did not increase the diagnostic specificity of coarctation, but isthmal flow disturbance increased the odds ratio of true coarctation versus arch hypoplasia 16-fold. CONCLUSIONS: Isthmal Z scores and isthmal-to-ductal ratio are sensitive indicators of fetal coarctation. Serial measurements and abnormal isthmal flow patterns improve diagnostic specificity and may reduce false positives.
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| 5. |
- Spencer, Rebecca N., et al.
(författare)
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Development of standard definitions and grading for Maternal and Fetal Adverse Event Terminology
- 2022
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Ingår i: Prenatal Diagnosis. - : Wiley. - 0197-3851 .- 1097-0223. ; 42:1, s. 15-26
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Adverse event (AE) monitoring is central to assessing therapeutic safety. The lack of a comprehensive framework to define and grade maternal and fetal AEs in pregnancy trials severely limits understanding risks in pregnant women. We created AE terminology to improve safety monitoring for developing pregnancy drugs, devices and interventions. Method: Existing severity grading for pregnant AEs and definitions/indicators of ‘severe’ and ‘life-threatening’ conditions relevant to maternal and fetal clinical trials were identified through a literature search. An international multidisciplinary group identified and filled gaps in definitions and severity grading using Medical Dictionary for Regulatory Activities (MedDRA) terms and severity grading criteria based on Common Terminology Criteria for Adverse Event (CTCAE) generic structure. The draft criteria underwent two rounds of a modified Delphi process with international fetal therapy, obstetric, neonatal, industry experts, patients and patient representatives. Results: Fetal AEs were defined as being diagnosable in utero with potential to harm the fetus, and were integrated into MedDRA. AE severity was graded independently for the pregnant woman and her fetus. Maternal (n = 12) and fetal (n = 19) AE definitions and severity grading criteria were developed and ratified by consensus. Conclusions: This Maternal and Fetal AE Terminology version 1.0 allows systematic consistent AE assessment in pregnancy trials to improve safety.
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