1. |
- Hellström, Ann, 1959, et al.
(author)
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Retrospective evaluation of ophthalmological and neurological outcomes for infants born before 24 weeks gestational age in a Swedish cohort
- 2022
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In: Bmj Open. - : BMJ. - 2044-6055. ; 12:8
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Journal article (peer-reviewed)abstract
- Objectives To retrospectively evaluate ophthalmological and neurological outcomes in a Swedish cohort of infants born before 24 weeks gestational age (GA) and explore risk factors for visual impairment. Setting Eye and paediatric clinics in Sweden. Participants Infants screened for retinopathy of prematurity (ROP) (n=399), born before 24 weeks GA, 2007-2018. Cases were excluded if ophthalmological follow-up records could not be traced. Primary and secondary outcome measures Primary outcomes were ophthalmological, including visual acuity (VA), refractive error, strabismus, nystagmus and cerebral visual impairment (CVI). Secondary outcomes comprised neonatal and neurological morbidities. Data were retrospectively retrieved from medical records. Results The 355 assessed children had a median GA of 23 weeks and 2 days and a median birth weight of 565 g. At the last available ophthalmological examination, the median age was 4.8 years (range 0.5-13.2 years). Nystagmus was recorded in 21.1%, strabismus in 34.8%, and 51.0% wore spectacles. Seventy-three of 333 (21.9%) were visually impaired, defined as being referred to a low vision clinic and/or having a VA less than 20/60 at 3.5 years of age or older. ROP treatment was a significant risk factor for visual impairment (OR 2.244, p=0.003). Visually impaired children, compared with children without visual impairment, more often had neurological deficits such as intellectual disability 63.8% versus 33.3% (p<0.001), epilepsy 21.1% versus 7.5% (p=0.001) and autism spectrum disorders 32.8% versus 20.9% (p=0.043). Nine of the 355 children had been diagnosed with CVI. Conclusions Children born before 24 weeks GA frequently had visual impairment in association with neurological deficits. CVI was rarely diagnosed. A multidisciplinary approach for the evaluation and habilitation of these vulnerable infants is warranted. National follow-up guidelines need to be developed and implemented.
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2. |
- Lundgren, Pia, et al.
(author)
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High rate and large intercentre variability in retreatment of retinopathy of prematurity in infants born < 24 gestational weeks
- 2021
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In: BMJ Open Ophthalmology. - : BMJ Publishing Group Ltd. - 2397-3269. ; 6:1
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Journal article (peer-reviewed)abstract
- Objective Prematurity is a major risk factor for retinopathy of prematurity (ROP). We aimed to elucidate ROP prevalence, treatment and retreatment in infants born before 24 gestational age (GA) weeks in a Swedish cohort. Methods and analysis Infants with completed ROP screening, born at <24 GA weeks, 2007-2018 in Sweden were included. Data of GA, birth weight (BW), sex, neonatal morbidities, maximal ROP stage, aggressive posterior ROP (APROP), ROP treatments, treatment modality and treatment centre were retrieved. Results In total, 399 infants, with a mean GA of 23.2 weeks (range 21.9-23.9) and a mean BW of 567 g (range 340-874), were included. ROP was detected in 365 (91.5%) infants, 173 (43.4%) were treated for ROP and 68 of 173 (39.3%) were treated more than once. As the first treatment, 142 (82.0%) received laser and 29 (16.1%) received intravitreal injection of antivascular endothelial growth factor (anti-VEGF). Retreatment was performed after first laser in 46 of 142 (32.4%) and in 20 of 29 (69.0%) after first anti-VEGF treatment. Retreatment rate was not associated with GA, BW or sex but with APROP, treatment method (anti-VEGF) and treatment centre where the laser was performed (p<0.001). Twenty eyes progressed to retinal detachment, and two infants developed unilateral endophthalmitis after anti-VEGF treatment. Conclusion Infants, born at <24 weeks GA, had high rates of treatment-warranting ROP and retreatments. Treatment centre highly influenced the retreatment rate after laser indicating that laser treatment could be improved in some settings.
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3. |
- Bjarnegård, Niclas, et al.
(author)
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Cardiovascular function in adulthood following intrauterine growth restriction with abnormal fetal blood flow
- 2013
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In: Ultrasound in Obstetrics and Gynecology. - : Wiley-Blackwell. - 0960-7692 .- 1469-0705. ; 41:2, s. 177-184
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Journal article (peer-reviewed)abstract
- Objectives To examine whether intrauterine growth restriction (IUGR) is associated with increased cardiovascular risk later in life. Methods We examined 19 young adults (aged 2225 years) who were born at term after IUGR, along with 18 controls. All had been examined previously with fetal Doppler, and in the present follow-up with echocardiography, carotid echo-tracking ultrasound, applanation tonometry, blood pressure and laser Doppler, in order to characterize their cardiac and vascular geometry and/or function. Results The diameter of the ascending aorta and the left ventricular diameter were smaller in the IUGR group, but only ascending aortic diameter remained significantly smaller after adjustment for body surface area (Pandlt;0.05). The aortic pressure augmentation index was higher in the IUGR group (Pandlt;0.05). The common carotid artery diameter, intimamedia thickness and distensibility as well as left ventricular mass and function were similar in the two groups. IUGR status was found to be an independent predictor of ascending aortic diameter. Conclusions IUGR due to placental dysfunction seems to contribute to the higher systolic blood pressure augmentation and the smaller aortic dimensions that are observed in adults more than 20 years later, with possible negative consequences for future left ventricular performance due to increased aortic impedance.
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4. |
- Brodszki, Jana, et al.
(author)
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Early intervention in management of very preterm growth-restricted fetuses : 2-year outcome of infants delivered on fetal indication before 30 gestational weeks
- 2009
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In: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705. ; 34:3, s. 288-296
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To describe the outcome of growth-restricted fetuses with absent or reversed end-diastolic flow (ARED) in the umbilical artery delivered on fetal indication before 30 gestational weeks.METHODS: Between 1998 and 2004, 42 fetuses with intrauterine growth restriction (IUGR) and ARED in the umbilical artery were delivered liveborn by Cesarean section on fetal indication before 30 gestational weeks. The median gestational age at delivery was 27 + 1 (range, 24 + 4 to 29 + 5) weeks. An additional four fetuses died in utero at a median gestational age of 24 + 2 (range, 23 + 5 to 25 + 4) weeks. Neonatal morbidity, infant mortality and major neurological morbidity of liveborn infants were compared with those in two control groups: all 371 liveborn infants delivered at < 30 weeks during the corresponding time period (Group A) and a subset of these, 42 matched infants without IUGR (Group B).RESULTS: Thirty-two fetuses (76%) [corrected] were delivered within 48 h of the occurrence of ARED (25 absent, seven reversed end-diastolic flow). The remaining 10 fetuses (five absent, five reversed end-diastolic flow) were monitored for a median of 6.5 (range, 3-18) days before delivery. One infant died in the neonatal period and three during the first year of postnatal life (2-year survival 90%). The incidence of chronic lung disease was higher in the ARED Group than in Control Groups A and B (P = 0.001 and P = 0.03, respectively). There were no differences between the groups in the occurrence of necrotizing enterocolitis, cerebral hemorrhage or retinopathy of prematurity. Cerebral palsy was diagnosed in 14% of the index group compared with 11% and 17% of Control Groups A and B (P > 0.05).CONCLUSIONS: Very preterm growth-restricted fetuses with umbilical artery ARED delivered on fetal indication, in most cases before the occurrence of severe changes in the ductus venosus velocity waveforms and/or fetal heart rate tracings, showed high 2-year survival and low morbidity.
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5. |
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6. |
- Hellström, William, et al.
(author)
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Fetal haemoglobin and bronchopulmonary dysplasia in neonates: An observational study
- 2021
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In: Archives of Disease in Childhood: Fetal and Neonatal Edition. - : BMJ. - 1359-2998 .- 1468-2052. ; 106, s. 88-92
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Journal article (peer-reviewed)abstract
- Objective: Early decrease in fetal haemoglobin (HbF) is an indicator of loss of endogenous blood components that might have predictive value for development of bronchopulmonary dysplasia (BPD). The link between HbF and BPD has not been evaluated. Design: Retrospective observational study. Setting: Tertiary level neonatal intensive care unit, referral centre for Southern Sweden. Patients: 452 very preterm infants (<30 gestational weeks) born 2009-2015. Interventions: Regular clinical practice. Main outcome measures: Mean HbF, haemoglobin (Hb) and partial oxygen pressure (PaO2) levels calculated from 11 861 arterial blood gas analyses postnatal week 1. Relationship between HbF (%) and BPD (requirement of supplemental oxygen at 36 weeks' postmenstrual age) and the modifying influence of PaO2 (kPa) and total Hb (g/L) was evaluated. Results: The mean gestational age (GA) at birth was 26.4 weeks, and 213 (56%) infants developed BPD. A 10% increase in HbF was associated with a decreased prevalence of BPD, OR 0.64 (95% CI 0.49 to 0.83; p<0.001). This association remained when adjusting for mean PaO2 and Hb. Infants with an HbF in the lowest quartile had an OR of 27.1 (95% CI 11.6 to 63.4; p<0.001) for development of BPD as compared with those in the highest quartile. The area under the curve for HbF levels and development of BPD in the full statistical model was 0.871. Conclusions: Early rapid postnatal decline in HbF levels was associated with development of BPD in very preterm infants. The association between HbF and BPD was not mediated by increased oxygen exposure. The potential benefit of minimising loss of endogenous blood components on BPD outcome will be investigated in a multicentre randomised trial. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
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7. |
- Hellström, William, et al.
(author)
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Low fraction of fetal haemoglobin is associated with retinopathy of prematurity in the very preterm infant
- 2022
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In: British Journal of Ophthalmology. - : BMJ. - 0007-1161 .- 1468-2079. ; 106, s. 970-974
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Journal article (peer-reviewed)abstract
- Background: Blood loss and adult blood transfusions are common during the neonatal period in preterm infants. The objective of the study was to clarify if degree of loss of fetal haemoglobin (HbF) was associated with later retinopathy of prematurity (ROP). Methods: Retrospective observational cohort study. In total, 452 infants born <30 gestational weeks at a tertiary level neonatal intensive care unit in Sweden in 2009-2015 were included, 385 of whom had final ROP outcome. Mean fractions of HbF (%) during the first postnatal week were calculated from 11 861 arterial blood gas analyses. The relationship between fractions of HbF (%) and ROP was evaluated. Results: The mean (SD) gestational age (GA) at birth was 26.4 (1.8) weeks. In total, 104 (27 %) infants developed ROP. Higher fraction of HbF (%) was associated with a lower prevalence of ROP, OR by a 10% increase 0.83 (95% CI: 0.71 to 0.97; p=0.019), following adjustment for GA at birth, small for GA and sex. Infants with HbF (%) in the lowest quartile had OR of 22.0 (95% CI: 8.1 to 59.2; p<0.001) for ROP development compared with those in the highest quartile. The predictive ability (area under the curve) of HbF (%) in the full model during the first week was 0.849 for ROP. Conclusions: Early low fraction of HbF is independently associated with abnormal retinal neurovascular development in the very preterm infant. The potential benefit of minimising blood loss on development of ROP will be investigated in a multicenter randomised trial (NCT04239690). © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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8. |
- Hellström, William, et al.
(author)
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Neonatal clinical blood sampling led to major blood loss and was associated with bronchopulmonary dysplasia
- 2020
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In: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 109:4, s. 679-687
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Journal article (peer-reviewed)abstract
- Aim: Studies indicate that reduced foetal haemoglobin levels are related to increased neonatal morbidity rates. This study investigated the relationships between sampling-related blood loss and adult blood transfusions administered during postnatal days 1-14 and the development of severe neonatal morbidities in extremely preterm infants born before 28 weeks of gestation. Methods: The medical files of 149 extremely preterm infants born at two university hospitals in Sweden from 2013 to 2018 were investigated. Results: Blood sampling resulted in a 58% depletion of the endogenous blood volume postnatal days 1-14 (median 40.4 mL/kg, interquartile range 23.9-53.3 mL/kg) and correlated with the adult erythrocyte transfusion volume (rS = 0.870, P <.001). Sampling-related blood loss on postnatal days 1-7, adjusted for gestational age at birth and birth weight standard deviation score, was associated with the development of bronchopulmonary dysplasia (BPD) (odds ratio by a 10-unit increase 2.4, 95% confidence interval 1.1-5.4) (P =.03). No associations were found between blood sampling and intraventricular haemorrhage or necrotising enterocolitis in the full statistical model. The largest proportion of sampling-related blood was used for blood gas analyses (48.7%). Conclusion: Diagnostic blood sampling led to major endogenous blood loss replaced with adult blood components and was associated with the development of BPD.
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9. |
- Liefke, Jonas, et al.
(author)
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Early-Onset Fetal Growth Restriction Increases Left Ventricular Sphericity in Adolescents Born Very Preterm
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In: Pediatric Cardiology. - 0172-0643.
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Journal article (peer-reviewed)abstract
- Left ventricular shape alterations predict cardiovascular outcomes and have been observed in children born preterm and after fetal growth restriction (FGR). The aim was to investigate whether left ventricular shape is altered in adolescents born very preterm and if FGR has an additive effect. Adolescents born very preterm due to verified early-onset FGR and two control groups with birthweight appropriate for gestational age (AGA), born at similar gestational age and at term, respectively, underwent cardiac MRI. Principal component analysis was applied to find the modes of variation best explaining shape variability for end-diastole, end-systole, and for the combination of both, the latter indicative of function. Seventy adolescents were included (13-16 years; 49% males). Sphericity was increased for preterm FGR versus term AGA for end-diastole (36[0-60] vs - 42[- 82-8]; p = 0.01) and the combined analysis (27[- 23-94] vs - 51[- 119-11]; p = 0.01), as well as for preterm AGA versus term AGA for end-diastole (30[- 56-115] vs - 42[- 82-8]; p = 0.04), for end-systole (57[- 29-89] vs - 30[- 79-34]; p = 0.03), and the combined analysis (44[- 50-145] vs - 51[- 119-11]; p = 0.02). No group differences were observed for left ventricular mass or ejection fraction (all p ≥ 0.33). Sphericity was increased after very preterm birth and exacerbated by early-onset FGR, indicating an additive effect to that of very preterm birth on left ventricular remodeling. Increased sphericity may be a prognostic biomarker of future cardiovascular disease in this cohort that as of yet shows no signs of cardiac dysfunction using standard clinical measurements.
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10. |
- Liefke, Jonas, et al.
(author)
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Fetal growth restriction followed by very preterm birth is associated with smaller kidneys but preserved kidney function in adolescence
- 2023
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In: Pediatric Nephrology. - : Springer Science and Business Media LLC. - 1432-198X .- 0931-041X. ; 38:6, s. 1855-1866
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Journal article (peer-reviewed)abstract
- Background: Preterm birth and fetal growth restriction (FGR) are associated with structural and functional kidney changes, increasing long-term risk for chronic kidney disease and hypertension. However, recent studies in preterm children are conflicting, indicating structural changes but normal kidney function. This study therefore assessed kidney structure and function in a cohort of adolescents born very preterm with and without verified FGR.Methods: Adolescents born very preterm with FGR and two groups with appropriate birthweight (AGA) were included; one matched for gestational week at birth and one born at term. Cortical and medullary kidney volumes and T1 and T2* mapping values were assessed by magnetic resonance imaging. Biochemical markers of kidney function and renin-angiotensin-aldosterone system (RAAS) activation were analyzed.Results: Sixty-four adolescents were included (13-16 years; 48% girls). Very preterm birth with FGR showed smaller total (66 vs. 75 ml/m2; p = 0.01) and medullary volume (19 vs. 24 ml/m2; p < 0.0001) compared to term AGA. Corticomedullary volume ratio decreased from preterm FGR (2.4) to preterm AGA (2.2) to term AGA (1.9; p = 0.004). There were no differences in T1 or T2* values (all p ≥ 0.34) or in biochemical markers (all p ≥ 0.12) between groups.Conclusions: FGR with abnormal fetal blood flow followed by very preterm birth is associated with smaller total kidney and medullary kidney volumes, but not with markers of kidney dysfunction or RAAS activation in adolescence. Decreased total kidney and medullary volumes may still precede a long-term decrease in kidney function, and potentially be used as a prognostic marker. A higher resolution version of the Graphical abstract is available as Supplementary information.
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11. |
- Liefke, Jonas, et al.
(author)
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Higher blood pressure in adolescent boys after very preterm birth and fetal growth restriction
- 2023
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In: Pediatric Research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 93:7, s. 2019-2027
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Journal article (peer-reviewed)abstract
- BackgroundAlthough preterm birth predisposes for cardiovascular disease, recent studies in children indicate normal blood pressure and arterial stiffness. This prospective cohort study therefore assessed blood pressure and arterial stiffness in adolescents born very preterm due to verified fetal growth restriction (FGR).MethodsAdolescents (14 (13–17) years; 52% girls) born very preterm with FGR (preterm FGR; n = 24) and two control groups born with appropriate birth weight (AGA), one in similar gestation (preterm AGA; n = 27) and one at term (term AGA; n = 28) were included. 24-hour ambulatory blood pressure and aortic pulse wave velocity (PWV) and distensibility by magnetic resonance imaging were acquired.ResultsThere were no group differences in prevalence of hypertension or in arterial stiffness (all p ≥ 0.1). In boys, diastolic and mean arterial blood pressures increased from term AGA to preterm AGA to preterm FGR with higher daytime and 24-hour mean arterial blood pressures in the preterm FGR as compared to the term AGA group. In girls, no group differences were observed (all p ≥ 0.1).ConclusionsVery preterm birth due to FGR is associated with higher, yet normal blood pressure in adolescent boys, suggesting an existing but limited impact of very preterm birth on cardiovascular risk in adolescence, enhanced by male sex and FGR.ImpactVery preterm birth due to fetal growth restriction was associated with higher, yet normal blood pressure in adolescent boys.In adolescence, very preterm birth due to fetal growth restriction was not associated with increased thoracic aortic stiffness.In adolescence, very preterm birth in itself showed an existing but limited effect on blood pressure and thoracic aortic stiffness.Male sex and fetal growth restriction enhanced the effect of preterm birth on blood pressure in adolescence.Male sex and fetal growth restriction should be considered as additional risk factors to that of preterm birth in cardiovascular risk stratification.
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12. |
- Liefke, Jonas, et al.
(author)
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Non-contrast-enhanced magnetic resonance imaging can be used to assess renal cortical and medullary volumes-A validation study
- 2022
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In: Acta Radiologica Open. - : SAGE Publications. - 2058-4601. ; 11:1, s. 1-8
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Journal article (peer-reviewed)abstract
- Background: Magnetic resonance imaging (MRI) biomarkers can diagnose and prognosticate kidney disease. Renal volume validation studies are however scarce, and measurements are limited by use of contrast agent or advanced post-processing.Purpose: To validate a widely available non-contrast-enhanced MRI method for quantification of renal cortical and medullary volumes in pigs; investigate observer variability of cortical and medullary volumes in humans; and present reference values for renal cortical and medullary volumes in adolescents.Materials and Methods: Cortical and medullary volumes were quantified from transaxial in-vivo water-excited MR images in six pigs and 15 healthy adolescents (13-16years). Pig kidneys were excised, and renal cortex and medulla were separately quantified by the water displacement method. Both limits of agreement by the Bland-Altman method and reference ranges are presented as 2.5-97.5 percentiles.Results: Agreement between MRI and ex-vivo quantification were -7 mL (-10-0 mL) for total parenchyma, -4 mL (-9-3 mL) for cortex, and -2 mL (-7-2 mL) for medulla. Intraobserver variability for pig and human kidneys were <5% for total parenchyma, cortex, and medulla. Interobserver variability for both pig and human kidneys were ≤4% for total parenchyma and cortex, and 6% and 12% for medulla. Reference ranges indexed for body surface area and sex were 54-103 mL/m2 (boys) and 56-103 mL/m2 (girls) for total parenchyma, 39-62 mL/m2 and 36-68 mL/m2 for cortex, and 16-45 mL/m2 and 17-42 mL/m2 for medulla.Conclusion: The proposed widely available non-contrast-enhanced MRI method can quantify cortical and medullary renal volumes and can be directly implemented clinically.
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13. |
- Lingam, Ingran, et al.
(author)
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Neonatal outcomes following early fetal growth restriction : a subgroup analysis of the EVERREST study
- 2023
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In: Archives of disease in childhood. Fetal and neonatal edition. - 1359-2998. ; 108:6, s. 599-606
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To quantify the risks of mortality, morbidity and postnatal characteristics associated with extreme preterm fetal growth restriction (EP-FGR).DESIGN: The EVERREST (Do e s v ascular endothelial growth factor gene therapy saf e ly imp r ove outcome in seve r e e arly-onset fetal growth re st riction?) prospective multicentre study of women diagnosed with EP-FGR (singleton, estimated fetal weight (EFW) <3rd percentile, <600 g, 20+0-26+6 weeks of gestation). The UK subgroup of EP-FGR infants (<36 weeks) were sex-matched and gestation-matched to appropriate for age (AGA) infants born in University College London Hospital (1:2 design, EFW 25th-75th percentile).SETTING: Four tertiary perinatal units (UK, Germany, Spain, Sweden).MAIN OUTCOMES: Antenatal and postnatal mortality, bronchopulmonary dysplasia (BPD), sepsis, surgically treated necrotising enterocolitis (NEC), treated retinopathy of prematurity (ROP).RESULTS: Of 135 mothers recruited with EP-FGR, 42 had a stillbirth or termination of pregnancy (31%) and 93 had live births (69%). Postnatal genetic abnormalities were identified in 7/93 (8%) live births. Mean gestational age at birth was 31.4 weeks (SD 4.6). 54 UK-born preterm EP-FGR infants (<36 weeks) were matched to AGA controls. EP-FGR was associated with increased BPD (43% vs 26%, OR 3.6, 95% CI 1.4 to 9.4, p=0.01), surgical NEC (6% vs 0%, p=0.036) and ROP treatment (11% vs 0%, p=0.001). Mortality was probably higher among FGR infants (9% vs 2%, OR 5.0, 95% CI 1.0 to 25.8, p=0.054). FGR infants more frequently received invasive ventilation (65% vs 50%, OR 2.6, 95% CI 1.1 to 6.1, p=0.03), took longer to achieve full feeds and had longer neonatal stays (median difference 6.1 days, 95% CI 3.8 to 8.9 and 19 days, 95% CI 9 to 30 days, respectively, p<0.0001).CONCLUSIONS: Mortality following diagnosis of EP-FGR is high. Survivors experience increased neonatal morbidity compared with AGA preterm infants.TRIAL REGISTRATION NUMBER: NCT02097667.
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14. |
- Lundgren, Pia, 1967, et al.
(author)
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National cohort of infants born before 24 gestational weeks showed increased survival rates but no improvement in neonatal morbidity
- 2022
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:8, s. 1515-1525
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Journal article (peer-reviewed)abstract
- Aim To describe survival and neonatal morbidities in infants born before 24 weeks of gestation during a 12-year period. Methods Data were retrieved from national registries and validated in medical files of infants born before 24 weeks of gestation 2007-2018 in Sweden. Temporal changes were evaluated. Results In 2007-2018, 282 live births were recorded at 22 weeks and 460 at 23 weeks of gestation. Survival to discharge from hospital of infants born alive at 22 and 23 weeks increased from 20% to 38% (p = 0.006) and from 45% to 67% (p < 0.001) respectively. Caesarean section increased from 12% to 22% (p = 0.038) for infants born at 22 weeks. Neonatal morbidity rates in infants alive at 40 weeks of postmenstrual age (n = 399) were unchanged except for an increase in necrotising enterocolitis from 0 to 33% (p = 0.017) in infants born at 22 weeks of gestation. Bronchopulmonary dysplasia was more common in boys than girls, 90% versus 82% (p = 0.044). The number of infants surviving to 40 weeks doubled over time. Conclusion Increased survival of infants born before 24 weeks of gestation resulted in increasing numbers of very immature infants with severe neonatal morbidities likely to have a negative impact on long-term outcome.
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15. |
- Morsing, Eva, et al.
(author)
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Brain volumes and developmental outcome in childhood following fetal growth restriction leading to very preterm birth
- 2018
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In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:NOV
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Journal article (peer-reviewed)abstract
- Background: Children born very preterm (PT) after fetal growth restriction (FGR) exhibit cognitive impairment at early school age. The relationship between neurodevelopmental impairment and attained regional brain volumes is unknown. Methods: We studied 23 preterm children with FGR (PT-FGR), 24 matched preterm children AGA (PT-AGA), and 27 matched term AGA children (T-AGA) by measuring brain volumes with magnetic resonance imaging at early school age. Cognitive and motor functions were assessed by the Wechsler Intelligence Scales for Children and the ABC-Movement score. Results: The mean (SD) full-scale IQ was 80 (17) in the PT-FGR group and 103 (12) in the PT-AGA group (p < 0.001). The PT-FGR group had lower mean total, gray matter, white matter, thalamic, cerebellar white matter, and hippocampal volumes as compared to the T-AGA group (p = 0.01, 0.04, 0.003, 0.002, 0.001, and 0.009, respectively). Brain volumes did not differ significantly between the PT groups. Reduction of hippocampal volume correlated with degree of growth restriction at birth (r = 0.46, p = 0.05). Neither the full-scale IQ nor the ABC movement score <5th percentile were related to brain volumes. Conclusion: Brain volumes as determined by MRI at early school age were primarily associated with degree of prematurity at birth and less with FGR. Regional brain volumes did not discriminate cognitive and motor function beyond that predicted by gestational age at birth.
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16. |
- Morsing, Eva, et al.
(author)
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Cardiovascular function in children born very preterm after intrauterine growth restriction with severely abnormal umbilical artery blood flow.
- 2014
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In: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 21:10, s. 1257-1266
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Journal article (peer-reviewed)abstract
- AIMS: Low birthweight has been linked to increased cardiovascular risk in adulthood. We evaluated the effect on cardiovascular outcome of intrauterine growth restriction (IUGR) with abnormal fetal blood flow in children born very preterm. METHODS: Blood pressure, cardiac function and size, diameters, distensibility, and stiffness of the abdominal aorta, carotid, and popliteal arteries, and endothelial function were assessed non-invasively in 7-year-old children (n = 32) born very preterm with IUGR, with birthweight (median, range) 650 g (395-976 g) and gestational age 27 weeks (24-29 weeks). In addition, intima-media thickness was measured in the carotid artery. Controls were matched for gender and age and had birthweight appropriate-for-gestational-age (AGA). The study included 32 preterm-AGA children with birthweight 1010 g (660-1790) g and 32 term-AGA children with birthweight 3530 g (3000-4390) g. RESULTS: Preterm-IUGR children had lower microvascular response to acetylcholine, lower aortic stiffness, and higher distensibility compared with the preterm-AGA group (p = 0.019, p = 0.001, and p < 0.001, respectively) and lower carotid intima-media thickness compared with the term-AGA group (p = 0.047). The highest aortic β and lowest distensibility were found in the preterm-AGA group. Height-adjusted systolic blood pressure was higher in the preterm groups than in the term-AGA group (p = 0.018). Cardiac function and size did not differ between the groups. CONCLUSION: IUGR and preterm birth appear to be associated with structural changes in the arterial wall, whereas preterm birth seems to be associated with higher blood pressure. Using conventional echocardiography, we observed no effect of IUGR on cardiac size and function.
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17. |
- Morsing, Eva, et al.
(author)
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Cognitive Function After Intrauterine Growth Restriction and Very Preterm Birth
- 2011
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 127:4, s. 874-882
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate the effects of intrauterine growth restriction (IUGR) with absent or reversed end-diastolic blood flow in the umbilical artery and very preterm birth on cognitive outcome at 5 to 8 years of age. METHODS: We studied 34 children with IUGR born at a median of 26.9 gestational weeks (GWs) (range: 24-29 GWs) (PT-IUGR), 34 matched preterm appropriate-for-gestational age (PT-AGA) children, and 34 term AGA children (T-AGA) by using the Wechsler Preschool and Primary Scale of Intelligence, Wechsler Intelligence Scale for Children, Strengths and Difficulties Questionnaire, and Brown's attention-deficit disorder (ADD) scales. RESULTS: The PT-IUGR group had mean (SD) scores on the verbal IQ (VIQ) and full-scale IQ (FSIQ) of 83.8 (17.3) and 78.9 (16.6), respectively, compared with the PT-AGA group, which had scores of 96.0 (14.5) and 90.1 (14.2) (P = .003 and P < .007), and the T-AGA group, which had scores of 101.3 (12) and 102.9 (13.2) (P < .001 and P < 001), respectively. The VIQ difference remained significant after adjustment for parental level of education, gestational age at birth, and neonatal morbidity. Performance IQ (PIQ) did not differ between the PT-IUGR and PT-AGA groups; their mean PIQs were lower than that of the T-AGA group (P < .001). Boys in the PT-IUGR group scored lower than girls in VIQ and FSIQ (P = .005 and .007, respectively). Behavior and ADD scores did not differ between the preterm groups. CONCLUSIONS: Children born very preterm after IUGR have an increased risk for cognitive impairment at early school age compared with children delivered very preterm for other reasons. Differences in cognitive outcome were restricted to boys who may have been especially vulnerable to the influence of IUGR and very preterm birth. Pediatrics 2011; 127: e874-e882
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18. |
- Morsing, Eva
(author)
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Development in children born very preterm after intrauterine growth restriction with abnormal fetal blood flow
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Delivery of fetuses with intrauterine growth restriction (IUGR) with abnormal umbilical artery blood flow in the second trimester represents a clinical dilemma. So far, no evidence based management protocols are available adressing when to deliver these fetuses. The high risk of hypoxia and fetal death has to be balanced against that of extreme preterm birth with associated morbidity. The clinical routine in Lund has been a proactive management, that is to deliver on fetal indication before occurence of more severe hemodynamic changes. The aim of this study was to evaluate short and long-term consequences in very preterm IUGR fetuses (PT-IUGR) with abnormal blood flow in the umbilical artery. Study I: Mortality and neonatal morbidity did not differ between the PT-IUGR group and the very preterm background population, born before 30 gestational weeks (GW) in 1998-2004, with the exception of chronic lung disease (p <0.01). Survival without major neurological handicap at two years was equal between the two groups. Study II: At early school age, cognitive impairment was more prevalent in boys born very preterm with IUGR compared to a matched very preterm group with BW appropriate for gestational age (PT-AGA). Attention deficit disorders were more prevalent in children in both preterm groups compared to term children with birth weight AGA (T-AGA) (p <0.01). There was a trend towards more behavioral problems in the preterm groups. Study III: Lung function, assessed with spirometry in children at 6-10 years, was reduced in the PT-IUGR group compared to the T-AGA group. The PT-IUGR group had worse lung function when born after 26 GW in comparison to the PT-AGA group (p<0.05). Study IV: Cardiovascular measurements were assessed at 5-8 years. Systolic and mean blood pressure, adjusted for height, was higher in both preterm groups compared to the T-AGA group (p<0.05). Findings in the vascular measurements were different between the preterm groups; the PT-IUGR group had lower aortic stiffness (p<0.01) and lower endothelial-dependent vasodilation compared to the PT-AGA group (p<0.05), and thinner intima media thickness in the carotid artery compared to the T-AGA group (p<0.05). Conclusions: IUGR in very preterm birth did not have an impact on overall mortality or major handicaps. Impairment in lung function was only apparent in the preterm IUGR group after 26 GW, a period of gestation when delivery on fetal indication in general is considered acceptable. The adverse impact of IUGR on cognitive function was present at all gestational ages, but cognitive impairment was only significant in IUGR boys compared to preterm controls. The question whether the cognitive impairment in boys is transient or persistent remains unanswered. It is difficult to understand the implication of the outcomes of lower IMT and aortic stiffness seen in the preterm IUGR group on later cardiovascular health. Further studies have to be performed in older ages. The observed outcome would not seem to be sufficiently severe to refrain from delivery in these very preterm IUGR fetuses and we suggest that it is justified to deliver fetuses with IUGR and abnormal blood flow in the umbilical artery at early gestational age in order to prevent intrauterine death.
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19. |
- Morsing, Eva, et al.
(author)
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Lung function in children born after foetal growth restriction and very preterm birth.
- 2012
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In: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 101:1, s. 48-54
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Journal article (peer-reviewed)abstract
- Aims: To assess lung function at early school age in children delivered at very early gestation owing to intrauterine growth restriction and abnormal foetal blood flow (IUGR). Methods: Spirometry was performed at median age 8.4 (range 6.5-10.7) years in 31 children born preterm with IUGR (PT-IUGR) with a median (range) birth weight (BW) of 650 (395-976)g and median (range) gestational age 27 (24-29)weeks. Control groups were matched for gender and age and had BW appropriate for gestational age (AGA); 31 children born preterm (PT-AGA) with BW of 1010 (660-1790)g matched for gestational age at birth, and 31 children born at term (T-AGA) with BW of 3530 (3000-4390)g. Results: The PT-IUGR group had lower mean (SD) values of z-scores for FEV(1) , FEV(1) /FVC and forced mid-expiratory flow rate (FEF(25-75%) ) compared to the T-AGA group, p=0.003, p=0.032 and p<0.001, respectively, but did not differ from the PT-AGA group. PT-IUGR children delivered at ≥26 gestational weeks (GW) had lower FEF(25-75%) than PT-AGA children of corresponding GA, p=0.014. Conclusion: Lung function was reduced in the PT-IUGR group at early school age compared to controls born at term. The influence of IUGR on later lung function was only apparent in children born preterm after 26 GW.
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20. |
- Morsing, Eva, et al.
(author)
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Neurodevelopmental disorders and somatic diagnoses in a national cohort of children born before 24 weeks of gestation
- 2022
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In: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:6, s. 1167-1175
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Journal article (peer-reviewed)abstract
- Aim: This study investigated childhood diagnoses in children born extremely preterm before 24 weeks of gestation. Methods: Diagnoses of neurodevelopmental disorders and selected somatic diagnoses were retrospectively retrieved from national Swedish registries for children born before 24 weeks from 2007 to 2018. Their individual medical files were also examined. Results: We studied 383 children born at a median of 23.3 (range 21.9–23.9) weeks, with a median birthweight of 565 (range 340–874) grams. Three-quarters (75%) had neurodevelopmental disorders, including speech disorders (52%), intellectual disabilities (40%), attention deficit hyperactivity disorder (30%), autism spectrum disorders (24%), visual impairment (22%), cerebral palsy (17%), epilepsy (10%) and hearing impairment (5%). More boys than girls born at 23 weeks had intellectual disabilities (45% vs. 27%, p < 0.01) and visual impairment (25% vs. 14%, p < 0.01). Just over half of the cohort (55%) received habilitation care. The majority (88%) had somatic diagnoses, including asthma (63%) and failure to thrive/short stature (39%). Conclusion: Most children born before 24 weeks had neurodevelopmental disorders and/or additional somatic diagnoses in childhood and were referred to habilitation services. Clinicians should be aware of the multiple health and developmental problems affecting these children. Resources are needed to identify their long-term support needs at an early stage.
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21. |
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22. |
- Morsing, Eva, et al.
(author)
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Reduced Prevalence of Severe Intraventricular Hemorrhage in Very Preterm Infants Delivered after Maternal Preeclampsia
- 2018
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In: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 114:3, s. 205-211
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Journal article (peer-reviewed)abstract
- Background: Very preterm (VPT) delivery after severe preeclampsia (PE) has been associated with adverse perinatal outcome. It is unclear whether fetal exposure to PE per se modifies the prevalence of neonatal morbidities associated with VPT birth. Objectives: To evaluate neonatal morbidity in VPT infants exposed to maternal PE compared to morbidity in nonexposed VPT infants. Methods: This retrospective study consisted of all inborn infants delivered before 30 gestational weeks admitted to a tertiary-level neonatal intensive care unit between 1998 and 2014: 195 infants exposed to maternal PE were compared to 957 infants without maternal PE (background group). Prevalence rates of neonatal morbidity, cerebral palsy (CP), and mortality at 2 years of age were obtained from patient records. Results: The PE group had a lower median (IQR) birth weight (795 [262] g) and a higher median gestational age (GA) (27 [3] weeks) at birth than the background group (890 [385] g and 26 [3] weeks, respectively; both p < 0.001). Exposure to maternal PE was associated with lower rates of severe intraventricular hemorrhage (IVH) (2 vs. 11%), retinopathy of prematurity requiring treatment (2 vs. 7%), mortality (9 vs. 15%), and CP (4 vs. 8%). Exposure to PE remained associated with a reduced prevalence of severe IVH (OR 0.17, 95% CI 0.05–0.57) after adjustment for GA, multiple birth, Apgar score, delivery mode, sex, and antenatal steroid treatment. Conclusion: Fetal exposure to PE is associated with a decreased rate of severe IVH following VPT birth. Studies on underlying mechanisms may provide a basis for prevention of IVH in the VPT infant.
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23. |
- Morsing, Eva, et al.
(author)
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[Survival and prematurity-related neonatal diagnoses among children born before 24 gestational weeks in Sweden 2007-2018]. : Allt fler barn födda före vecka 24 överlever, men sjukligheten är hög.
- 2023
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In: Lakartidningen. - 1652-7518. ; 120:10-11
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Journal article (peer-reviewed)abstract
- Children born before 24 gestational weeks had high neonatal morbidity and a majority had one or more neurodevelopmental disorders in addition to somatic diagnoses in childhood. Active Swedish perinatal care of infants with gestational age <24 weeks has resulted in a survival rate of more than 50 percent. Resuscitation of these immature infants is controversial, and some countries offer comfort care only. In a retrospective review of medical files and registries of 399 Swedish infants born before 24 gestational weeks, a majority had severe prematurity-related neonatal diagnoses. In childhood (2-13 years), 75 percent had at least one neurodevelopmental disorder and 88 percent had one or more prematurity-related somatic diagnosis (permanent or transient) that was likely to affect their quality of life. Long-term consequences for surviving infants should be considered in general recommendations as well as in parental information.
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24. |
- Spencer, Rebecca, et al.
(author)
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EVERREST prospective study : A 6-year prospective study to define the clinical and biological characteristics of pregnancies affected by severe early onset fetal growth restriction
- 2017
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In: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: Fetal growth restriction (FGR) is a serious obstetric condition for which there is currently no treatment. The EVERREST Prospective Study has been designed to characterise the natural history of pregnancies affected by severe early onset FGR and establish a well phenotyped bio-bank. The findings will provide up-to-date information for clinicians and patients and inform the design and conduct of the EVERREST Clinical Trial: a phase I/IIa trial to assess the safety and efficacy of maternal vascular endothelial growth factor (VEGF) gene therapy in severe early onset FGR. Data and samples from the EVERREST Prospective Study will be used to identify ultrasound and/or biochemical markers of prognosis in pregnancies with an estimated fetal weight (EFW) <3rd centile between 20+0 and 26+6 weeks of gestation. Methods: This is a 6 year European multicentre prospective cohort study, recruiting women with a singleton pregnancy where the EFW is <3rd centile for gestational age and <600 g at 20+0 to 26+6 weeks of gestation. Detailed data are collected on: maternal history; antenatal, peripartum, and postnatal maternal complications; health economic impact; psychological impact; neonatal condition, progress and complications; and infant growth and neurodevelopment to 2 years of corrected age in surviving infants. Standardised longitudinal ultrasound measurements are performed, including: fetal biometry; uterine artery, umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry; and uterine artery and umbilical vein volume blood flow. Samples of maternal blood and urine, amniotic fluid (if amniocentesis performed), placenta, umbilical cord blood, and placental bed (if caesarean delivery performed) are collected for bio-banking. An initial analysis of maternal blood samples at enrolment is planned to identify biochemical markers that are predictors for fetal or neonatal death. Discussion: The findings of the EVERREST Prospective Study will support the development of a novel therapy for severe early onset FGR by describing in detail the natural history of the disease and by identifying women whose pregnancies have the poorest outcomes, in whom a therapy might be most advantageous. The findings will also enable better counselling of couples with affected pregnancies, and provide a valuable resource for future research into the causes of FGR. Trial registration:NCT02097667registered 31st October 2013.
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25. |
- Tolockiene, Egle, et al.
(author)
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Intrauterine infection may be a major cause of stillbirth in Sweden
- 2001
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 80:6, s. 511-518
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Journal article (peer-reviewed)abstract
- Aim of the study. To investigate intrauterine infection as a cause for unexplained stillbirth. Methods. Chorioamnionitis was studied in a material of stillbirths (117 subjects from the years 1985-1994) from a region in the south Sweden. Control material (126 alive and healthy newborns and with healthy mothers) was gathered from the same region. Results. Chorioamnionitis was a common diagnosis both with stillbirths and 'healthy' deliveries (82 and 68%, respectively). Extension of the inflammation to decidua basalis was seven times more common among stillbirths than among controls (odds ratio 7.2, confidence interval 2.8-21.9). The most common bacteria found at cultures were Escherichia coli , Coagulase negative staphylococcus, Enterococcus faecalis and group B Streptococcus. The risk for stillbirth was doubled if both inflammation and bacteria were present (odds ratio 2.3, confidence interval 0.92-5.8). Meconium discharge was more common among stillbirths than controls (odds ratio=4.7, confidence interval 1.7-14). There were no differences in any respect regarding macerated and non-macerated stillbirths. Our findings are similar to the results from studies in developing countries except for the higher incidence of stillbirths in such countries. Conclusions. Thus, a large part of otherwise unexplained stillbirths might be due to ascending infections.
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