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  • 1.
    Austeng, Dordi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Blennow, Mats
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Fellman, Vineta
    Fritz, Thomas
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellström, Ann
    Holmgren, Per Ake
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Jakobsson, Peter
    Jeppsson, Annika
    Johansson, Kent
    Kallen, Karin
    Lagercrantz, Hugo
    Laurini, Ricardo
    Lindberg, Eva
    Lundqvist, Anita
    Marsal, Karel
    Nilstun, Tore
    Nordén Lindeberg, Solveig
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Norman, Mikael
    Olhager, Elisabeth
    Oestlund, Ingrid
    Serenius, Fredrik
    Simic, Marija
    Sjörs, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Stigson, Lennart
    Stjernqvist, Karin
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Tornqvist, Kristina
    Wennergren, Margareta
    Wallin, Agneta
    Westgren, Magnus
    Incidence of and risk factors for neonatal morbidity after active perinatal care: extremely preterm infants study in Sweden (EXPRESS)2010In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 99, no 7, p. 978-992Article in journal (Refereed)
    Abstract [en]

    Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.

  • 2.
    Austeng, Dordi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Källen, Karin
    Hellström, Ann
    Jakobsson, Peter
    Lundgren, Pia
    Tornqvist, Kristina
    Wallin, Agneta
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Regional differences in screening for retinopathy of prematurity in infants born before 27 weeks' gestation in Sweden: the EXPRESS study2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 4, p. 311-315Article in journal (Refereed)
    Abstract [en]

    Purpose:  The primary aim was to analyse regional incidences of retinopathy of prematurity (ROP) and frequencies of treatment and their relation to perinatal risk factors during a 3-year period. A secondary aim was to study adherence to the study screening protocol in the different regions.

    Methods:  A population-based study of neonatal morbidity in extremely preterm infants in Sweden (EXPRESS) was performed during 2004–2007. Screening for ROP was to start at postnatal age 5 weeks and to continue weekly until the retina was completely vascularized or until regression of ROP. Logistic regression analyses were used for evaluation of differences in incidence of Any ROP, ROP 3 or more and ROP Type 1 between the seven regions of the country.

    Results:  The regional incidence of ROP varied between 54% and 92% for Any ROP, between 25% and 43% for ROP stage 3 or more and between 8% and 23% of infants with ROP Type 1, all of whom were treated. There was no significant difference between the regions regarding ROP Type 1, even when adjusting for known risk factors for ROP.

    Conclusion:  The heterogeneity between the regions regarding the incidence of ROP was reduced with increasing severity of ROP, and there was no heterogeneity regarding frequency of treatment for ROP, which is the most important issue for the children. We cannot exclude observer bias regarding mild ROP and ROP stage 3 in this study.

  • 3. Bonamy, Anna-Karin E.
    et al.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Stephansson, Olof
    Ludvigsson, Jonas F.
    Cnattingius, Sven
    Preterm Birth and Later Retinal Detachment2013In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 120, no 11, p. 2278-2285Article in journal (Refereed)
    Abstract [en]

    Objective: Ophthalmologic complications after preterm birth are common. Small studies show an association between retinopathy of prematurity and later retinal detachment. There are no population-based studies of preterm birth and risk of retinal detachment, which was the objective of the current investigation.

    Design: Nationwide Swedish cohort study based on population registries.

    Participants: Of 3 423 697 subjects born in Sweden, 1 271 725 were born between 1973 and 1986 (i.e., before the national screening program for retinopathy of prematurity started), and 2 151 972 were born between 1987 and 2008. The participants were followed up from 1 year of age until 2009.

    Methods: Unadjusted and adjusted hazard ratios (HRs) for retinal detachment were calculated using Cox proportional hazards regression.

    Main Outcome Measures: Incident retinal detachment, as defined by a diagnosis in the Swedish Patient Register (both inpatient and hospital-based outpatient data).

    Results: During follow-up (median follow-up, 17.4 years), 1749 subjects were diagnosed with retinal detachment. Among the 188 852 subjects born prematurely (i.e., at < 37 weeks of gestation), there were 124 cases of retinal detachment, of which 42 occurred in the 20 470 subjects born before 32 weeks of gestation. Compared with subjects born at term (37-41 weeks), the adjusted HR for retinal detachment after extremely preterm birth (< 28 weeks of gestation) was 19.2 (95% confidence interval [CI], 10.3-35.8) for births between 1973 and 1986 and 8.95 (95% CI, 3.98-20.1) for births between 1987 and 2008. The corresponding HRs in subjects born very prematurely (28-31 weeks) were 4.32 (95% CI, 2.70-6.90) and 2.80 (95% CI, 1.38-5.69), respectively. Moderately preterm birth (32-36 weeks) was not associated with an increased risk of retinal detachment.

    Conclusions: Birth before 32 weeks of gestation is associated with a substantially increased relative risk of retinal detachment. These findings may have implications for ophthalmologic follow-up of children and adults born very prematurely. 

  • 4.
    Brodd, Katarina Strand
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Grönqvist, Helena
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Grönqvist, Erik
    Uppsala University, Units outside the University, Office of Labour Market Policy Evaluation.
    von Hofsten, Claes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Rosander, Kerstin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Development of smooth pursuit eye movements in very preterm infants: 1. General aspects2011In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 100, no 7, p. 983-991Article in journal (Refereed)
    Abstract [en]

    Aim:  To investigate early oculo-motor development in a population-based cohort of very preterm infants.

    Methods:  Early oculo-motor development was prospectively studied by measuring smooth pursuit eye movements at 2 and 4 months corrected age in a population of very preterm infants born in Uppsala County 2004–2007. Eighty-one preterm infants were studied, and 32 healthy term infants constituted the control group.

    Results:  The study group consisted of infants with a mean gestational age of28 + 5 weeks. At 2 and 4 months corrected age, infants born very preterm showed lower gain (p < 0.001) and proportion of smooth pursuit eyemovements (p < 0.001) compared to the control group. The boys showed higher gain of smooth pursuit eye movements at both 2 and 4 months corrected age, compared to girls.

    Conclusions:  Oculo-motor development measured by smooth pursuit eye movements is delayed in very preterm infants at 2 and 4 months corrected age. This might be a risk factor or early indicator of later perceptual and behavioural impairment.

  • 5.
    Brodd, Katarina Strand
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Grönqvist, Helena
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Grönqvist, Erik
    Uppsala University, Units outside the University, Office of Labour Market Policy Evaluation.
    Rosander, Kerstin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Development of Smooth Pursuit Eye Movements in very preterm born infants: 3. Association to perinatal risk factors2012In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 101, no 2, p. 164-171Article in journal (Refereed)
    Abstract [en]

    Aim:  To investigate the association between perinatal risk factors and neonatal complications and early oculo-motor development in very preterm infants.

    Methods:  Perinatal risk factors were identified, and the potential association with early oculo-motor development was evaluated by measuring smooth pursuit eye movements (SP) at 2 and 4 months' corrected age (CA) in a population of very preterm infants born in Uppsala County 2004-2007 (n = 113).

    Results:  Among the 15 tested factors, eight showed significant association in univariate analysis with lower levels of SP at 4 months' CA, namely administration of prenatal corticosteroids, gestational age, birthweight, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, intraventricular haemorrhage >grade 2, and persistent ductus arteriosus. At 2 months' CA, only retinopathy of prematurity >stage 2 was associated with lower levels of SP. When all factors significant in the univariate tests were included in multiple regressions aimed to assess each factor's independent relation to SP, periventricular leukomalacia was the only significant independent factor. When adding 2-5 of the significant factors using multiple regression analysis, the levels of SP became lower.

    Conclusion:  Perinatal risk factors were associated with lower levels of SP. This could be interpreted as delayed or disturbed development of normal oculomotor ability.

  • 6.
    Fahnehjelm, Kristina Tear
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;St Erik Eye Hosp, Stockholm, Sweden.;Univ Gothenburg, Sahlgrenska Akad, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Liu, Ying
    Karolinska Univ Hosp, Dept Clin Neurophysiol, Huddinge, Sweden.;Soder Sjukhuset, Dept Ophthalmol, Stockholm, Sweden..
    Olsson, David
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Paediat, Stockholm, Sweden..
    Amren, Urban
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;St Erik Eye Hosp, Stockholm, Sweden..
    Haglind, Charlotte Bieneck
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Paediat, Stockholm, Sweden..
    Holmström, Gerd
    Univ Uppsala Hosp, Dept Neurosci Ophthalmol, Uppsala, Sweden..
    Halldin, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Andreasson, Sten
    Lund Univ, Dept Ophthalmol, Lund, Sweden..
    Nordenstrom, Anna
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Paediat, Stockholm, Sweden..
    Most patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency develop pathological or subnormal retinal function2016In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 105, no 12, p. 1451-1460Article in journal (Refereed)
    Abstract [en]

    Aim: There have been few studies on long-term electroretinographic findings in patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). This study correlated long-term electroretinographic findings with age, metabolic control and clinical symptoms. Methods: We examined 12 Swedish patients with LCHADD. Visual acuity testing, fundus examinations, optical coherence tomography and electroretinography were performed. The results were correlated to age, the levels of 3-hydroxyacylcarnitine and acylcarnitine and clinical metabolic control. Results: Blindness or moderate visual impairment was found in two patients. Retinal pigmentation, atrophy and fibrosis were present in 11, seven and one of the patients, respectively, and optical coherence tomography showed retinal thinning in three of the six patients examined. Electroretinography was performed on 11 of the 12 patients. It was pathological, with reduced rod and cone responses, in five patients, subnormal in four and was related to poor clinical metabolic control and severe neonatal symptoms. Repeated electroretinographies revealed reduced function with increasing age. Conclusion: More than 80% of the LCHADD patients developed pathological or subnormal retinal function. This was more pronounced in patients with neonatal symptoms, but ameliorated by strict dietary treatment. Annual ophthalmological follow-ups, with electroretinography every second or third year, are recommended.

  • 7. Gole, Glen A.
    et al.
    Ells, Anna L.
    Katz, Ximena
    Holmström, Gerd
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Oftalmiatrik.
    Fielder, Alistair R.
    Capone, Antonio
    Flynn, John T.
    Good, William G.
    Holmes, Jonathan M.
    McNamara, J. Arch
    Palmer, Earl A.
    Quinn, Graham E.
    Shapiro, Michael J.
    Trese, Michael G. J.
    Wallace, David K.
    The International Classification of Retinopathy of Prematurity Revisited: An International Committee for the Classification of Retinopathy of Prematurity2005In: Arch Ophthalmol, Vol. 123, p. 991-999Article in journal (Refereed)
  • 8.
    Hellgren, Kerstin M.
    et al.
    Astrid Lindgren Childrens Hosp, Dept Clin Neurosci, Karolinska Inst, MBC, Polhemsgatan 56, S-11282 Stockholm, Sweden..
    Tornqvist, Kristina
    Univ Lund Hosp, Dept Ophthalmol, S-22185 Lund, Sweden..
    Jakobsson, Peter G.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Lundgren, Pia
    Umea Univ, Dept Ophthalmol, S-90187 Umea, Sweden..
    Carlsson, Birgitta
    Univ Orebro, Dept Ophthalmol, SE-70182 Orebro, Sweden..
    Kallen, Karin
    Lund Univ, Dept Obstet & Gynecol, Ctr Reprod Epidemiol, Lund, Sweden..
    Serenius, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellstrom, Ann
    Univ Gothenburg, Sahlgrenska Acad, Sect Pediat Ophthalmol, Gothenburg, Sweden..
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ophthalmologic Outcome of Extremely Preterm Infants at 6.5 Years of Age Extremely Preterm Infants in Sweden Study (EXPRESS)2016In: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 134, no 5, p. 555-562Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE This follow-up study of extremely preterm (EPT) children (<27 weeks' gestational age [GA] at birth) revealed major eye and visual problems in 37.9%(147 of 388) of all EPT infants and in 55.4%(67 of 121) of the most immature subgroups at 6.5 years of age. These major eye and visual problems were strongly associated with treatment-requiring retinopathy of prematurity (ROP). OBJECTIVES To investigate the ophthalmologic outcome of a national cohort of EPT children at 6.5 years of age and to evaluate the impact of prematurity and ROP. DESIGN, SETTING, AND PARTICIPANTS All surviving EPT children born in Sweden between April 1, 2004, and March 31, 2007, were included and compared with a matched term control group, as part of a prospective national follow-up study. MAIN OUTCOMES AND MEASURES Visual acuity, refraction in cycloplegia, and manifest strabismus were evaluated and compared with GA at birth and with treatment-requiring ROP. RESULTS The study cohort comprised 486 participants. The mean (SD) GA of the children who were included was 25 (1) weeks, and 45.7%(222 of 486) were female. At a median age of 6.6 years, 89.3%(434 of 486) of eligible EPT children were assessed and compared with 300 control group children. In the EPT group, 2.1%(9 of 434) were blind, 4.8%(21 of 434) were visually impaired according to the World Health Organization criteria, and 8.8% (38 of 434) were visually impaired according to the study criteria. Strabismus was found in 17.4% (68 of 390) and refractive errors in 29.7%(115 of 387) of the EPT children compared with 0% (0 of 299) and 5.9% (17 of 289), respectively, of the control children (P<.001). Altogether at 6.5 years of age, 37.9%(147 of 388) of the EPT children had some ophthalmologic abnormality compared with 6.2%(18 of 290) of the matched control group (95% CI of the difference, 26.1%-37.2%). When treatment-requiring ROP was adjusted for, no significant association between GA and visual impairment could be detected. For refractive errors, the association with GA remained after adjustment for treatment-requiring ROP (odds ratio, 0.72; 95% CI, 0.58-0.91 for each 1-week increment). CONCLUSIONS AND RELEVANCE In a Swedish national cohort of EPT children at 6.5 years of age, major eye and visual problems were frequently found. Treatment-requiring ROP was a stronger impact factor than GA on visual impairment and strabismus, but not on refractive errors, as a whole. In modern neonatal intensive care settings, ophthalmologic problems continue to account for a high proportion of long-term sequelae of prematurity.

  • 9.
    Hellström, Ann
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Sect Pediat Ophthalmol, Gothenburg, Sweden.
    Källen, Karin
    Lund Univ, Ctr Reprod Epidemiol, Lund, Sweden.
    Carlsson, Birgitta
    Örebro Univ, Dept Ophthalmol, Örebro, Sweden.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Jakobsson, Peter
    Linköping Univ, Dept Clin & Expt Med, Linköping, Sweden.
    Lundgren, Pia
    Umeå Univ, Dept Clin Sci, Ophthalmol, Umeå, Sweden.
    Serenius, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Stjernqvist, Karin
    Lund Univ, Dept Psychol, Lund, Sweden.
    Tornqvist, Kristina
    Lund Univ Hosp, Dept Ophthalmol, Lund, Sweden.
    Hellgren, Kerstin
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Extreme prematurity, treated retinopathy, bronchopulmonary dysplasia and cerebral palsy are significant risk factors for ophthalmological abnormalities at 6.5 years of age2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 5, p. 811-821Article in journal (Refereed)
    Abstract [en]

    Aim: This study evaluated the contributions of various prenatal and postnatal predictive factors to a documented high prevalence of ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm.

    Methods: We carried out a prospective population‐based study of all children born in Sweden at a gestational age of 22 + 0 to 26 + 6 weeks based on the Extremely Preterm Infants in Sweden Study. The main outcome measures were a combined score of visual impairment, refractive errors and strabismus at 6.5 years of age. Models of univariate and multivariable regression were used to analyse potential prenatal and postnatal predictive factors at different clinically relevant time‐points from one minute after birth to 30 months.

    Results: We focused on 399 known extremely preterm survivors and compared them to 300 full‐term controls. Significant antecedents for ophthalmological abnormalities included prematurity per se, retinopathy of prematurity that required treatment, severe bronchopulmonary dysplasia and cerebral palsy. Severe intraventricular haemorrhage was no longer a significant risk factor when we adjusted it for the 30‐month cognitive and neuromotor development outcomes.

    Conclusion: This time‐course risk analysis model showed a changing panorama of significant risk factors for ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm.

  • 10.
    Holmström, Gerd
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Oftalmiatrik.
    Horner's syndrome: an atypical presentation in a child with neurofibromatosis type 22006In: Eye, Vol. 20, p. 1472-1474Article in journal (Refereed)
  • 11.
    Holmström, Gerd E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Hellström, Ann
    Jakobsson, Peter G.
    Lundgren, Pia
    Törnqvist, Kristina
    Wallin, Agneta
    Swedish National Register for Retinopathy of Prematurity (SWEDROP) and the Evaluation of Screening in Sweden2012In: Archives of ophthalmology (1960), ISSN 0003-9950, Vol. 130, no 11, p. 1418-1424Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate screening for retinopathy of prematurity (ROP) in Sweden and to investigate possible modifications of the present screening guidelines. Methods: Infants in Sweden with a gestational age (GA) of 31 weeks + 6 days or less are screened for ROP. Data from the Swedish national register for ROP (SWEDROP) during 2008 and 2009 were extracted and compared with a national perinatal quality register. Results: In SWEDROP, there were 1791 infants born before a GA of 32weeks from January 1, 2008, through December 31, 2009. Another 70 infants were registered in the perinatal quality register but not in SWEDROP (drop-out rate, 3.8% [70 of 1861 infants]). Seven infants died before termination of screening. In the final study cohort (1784 infants), 15.6% had mild ROP and 8.5% had severe ROP. Treatment was performed in 4.4% of the infants, none of whom had a GA at birth of more than 28 weeks. Nine infants with a GA of more than 28 weeks at birth developed stage 3 ROP, which regressed spontaneously. The total number of examinations was 9286 (964 in infants with a GA of 31 weeks), and the mean (range) number of examinations of each infant was 5.2 (1-30). Conclusions: The SWEDROP, a quality register for ROP, has a national coverage (ie, participation) of 96%. Data from 2008 to 2009 show that it seems possible to reduce the upper limit for screening in Sweden by 1 week, including only infants with a GA of 30 weeks + 6 days or less. However, such a change should be combined with a strong recommendation to neonatologists to refer also severely ill and more "mature" infants.

  • 12.
    Holmström, Gerd E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Källen, Karin
    Centre of Reproductive Epidemiology, Lund University, Sweden.
    Hellström, Ann
    Section of Pediatric Ophthalmology, The Queen Silvia Children’s Hospital, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Jakobsson, Peter G
    Department of Clinical and Experimental Medicine, Linköping University, Sweden.
    Serenius, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Stjernqvist, Karin
    Department of Psychology, Lund University, Sweden.
    Tornqvist, Kristina
    Department of Ophthalmology, Lund University Hospital, Sweden.
    Ophthalmologic Outcome at 30 Months' Corrected Age of a Prospective Swedish Cohort of Children Born Before 27 Weeks of Gestation: The Extremely Preterm Infants in Sweden Study.2014In: JAMA ophthalmology, ISSN 2168-6173, Vol. 132, no 2, p. 182-189Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE

    Follow-up at 30 months' corrected age reveals eye and visual problems in one-third of children born extremely prematurely (&lt;27 weeks' gestation).

    OBJECTIVE

    To investigate the ophthalmologic outcome of extremely preterm children at 30 months' corrected age.

    DESIGN, SETTING, AND PARTICIPANTS

    A prospective, population-based follow-up study (Extremely Preterm Infants in Sweden Study [EXPRESS]) was conducted in Sweden. The population included extremely preterm infants (&lt;27 weeks' gestation) born in Sweden between 2004 and 2007, of whom 491 survived until age 2.5 years. Screening for retinopathy of prematurity (ROP) was performed in the neonatal period. At 30 months' corrected age, an ophthalmologic assessment was performed in 411 of 491 children (83.7%).

    MAIN OUTCOMES AND MEASURES

    Visual acuity, manifest strabismus, and refractive errors were evaluated.

    RESULTS

    Visual impairment was identified in 3.1% of the children, and 1.0% were blind. Refractive errors, defined as myopia less than -3 diopters (D), hypermetropia greater than +3 D, astigmatism 2 D or more, and/or anisometropia 2 D or more, were found in 25.6% of the children, and 14.1% had manifest strabismus. There were significant associations between visual impairment and treated ROP (P = .02), cognitive disability (P &lt; .001), and birth weight (P = .02). Multiple regression analyses revealed significant associations between strabismus and treated ROP (P &lt; .001), cognitive disability (P &lt; .01), and cerebral palsy (P = .02). Refractive errors were significantly correlated with severity of ROP (right eye, P &lt; .001; left eye, P &lt; .01). Children who had been treated for ROP had the highest frequency (69.0%) of eye and visual abnormalities.

    CONCLUSIONS AND RELEVANCE

    One-third of the extremely prematurely born children in this study had some kind of eye or visual problems, such as visual impairment, strabismus, or major refractive error. Despite being born extremely preterm, the present cohort has a similar prevalence of blindness and visual impairment as in previous Swedish cohorts of children born less prematurely.

    Various neurologic, cognitive, and behavioral sequels are well-known complications of premature birth.1- 3 Ophthalmologic problems are also well known, with retinopathy of prematurity (ROP) being the major threat in the neonatal period and an important cause of childhood blindness worldwide.4 In older children, an increase in strabismus and refractive errors, as well as deficiencies in visual acuity, contrast sensitivity, stereopsis, visual fields, accommodation, and visual perception, have been shown in various long-term population-based studies.5- 10

    Modern neonatal care is continuously improving, providing us with a new population of survivors born extremely preterm. The long-term outcome of this group of children is of utmost interest. A prospective national study (Extremely Preterm Infants in Sweden Study [EXPRESS])11- 13 of Swedish infants with a gestational age (GA) of less than 27 weeks born during 2004-2007 revealed high survival (70%) and high incidences of severe (35%) and treatment-requiring (20%) ROP. In an ongoing, long-term follow-up of this cohort, the neurologic and developmental outcome at 30 months’ corrected age has recently been reported.14 The present study aimed to investigate the ophthalmologic outcome of this group of extremely preterm children.

  • 13.
    Holmström, Gerd
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Hellstrom, A.
    Univ Gothenburg, Sahlgrenska Acad, Queen Silvia Childrens Hosp, Sect Pediat Ophthalmol, Gothenburg, Sweden..
    Jakobsson, P.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Lundgren, P.
    Umea Univ, Dept Clin Sci & Ophthalmol, Umea, Sweden..
    Tornqvist, K.
    Univ Lund Hosp, Dept Ophthalmol, Lund, Sweden..
    Wallin, A.
    St Erik Eye Hosp, Stockholm, Sweden..
    Screening for retinopathy of prematurity can be started in postmenstrual week 31 in very premature babies!2016In: Eye (London. 1987), ISSN 0950-222X, E-ISSN 1476-5454, Vol. 30, no 11, p. 1524-1525Article in journal (Refereed)
  • 14.
    Holmström, Gerd
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Hellström, Ann
    Jakobsson, Peter
    Lundgren, Pia
    Tornqvist, Kristina
    Wallin, Agneta
    Evaluation of new guidelines for ROP screening in Sweden using SWEDROP - a national quality register2015In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 3, p. 265-268Article in journal (Refereed)
    Abstract [en]

    PurposeTo investigate whether recent Swedish guidelines for Retinopathy of Prematurity (ROP) screening, that is, a gestational age (GA) at birth of <31weeks (w), are applicable in a new national cohort of prematurely born infants. MethodsSWEDROP is a national register for ROP, initiated in 2006. The present paper reports on data from the register on various aspects of screening for ROP in infants born between 2010 and 2011 and compares the results with those for a previously published cohort born between 2008 and 2009. ResultsDuring the study period, 1744 infants were screened for ROP. Mean GA was 28.4w (22-31), and mean birth weight was 1239g (382-2615). Screening started at postnatal age (PNA) 5.4w (0.4-13.3) and postmenstrual age (PMA) 33.8 w (24.9-50.1) Mean number of examinations was 5.4 per infant (1-38). Mild (stages 1-2) and severe ( stage 3) ROP was found in 15.4% and 8.7%, respectively. Treatment was performed in 4.2% (73/1744) of the infants, but in none with a GA of 30weeks or more. The first treatment was performed at a mean PNA and PMA of 12.7 w (7.7-25.4) and 37.4 w (32.1-51.4), respectively. ConclusionsRecently introduced new guidelines for ROP screening in Sweden remain applicable. Reassuringly, in infants born between 2010 and 2011, incidence of ROP, frequency and timing of treatment, frequency and timing of examinations and national coverage of ROP screening remained almost identical to those for a previous cohort from 2008 to 2009. The two SWEDROP cohorts provide a basis for discussion among Swedish ophthalmologists and neonatologists on the question of further lowering the upper screening limit with 1week.

  • 15.
    Holmström, Gerd
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Hellström, Ann
    Univ Gothenburg, Sahlgrenska Acad, Queen Silvia Childrens Hosp, Sect Pediat Ophthalmol, Gothenburg, Sweden..
    Jakobsson, Peter
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Lundgren, Pia
    Umea Univ, Ophthalmol, Dept Clin Sci, Umea, Sweden..
    Tornqvist, Kristina
    Univ Lund Hosp, Dept Ophthalmol, Lund, Sweden..
    Wallin, Agneta
    St Erik Eye Hosp, Stockholm, Sweden..
    Five years of treatment for retinopathy of prematurity in Sweden: results from SWEDROP, a national quality register2016In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 100, no 12, p. 1656-1661Article in journal (Refereed)
    Abstract [en]

    Background/aims Retinopathy of prematurity (ROP) is a sight-threatening disease, requiring efficient screening and treatment. The present study aims to describe various aspects on treatment for ROP in Sweden. Methods Data on treatment for ROP in infants born in 2008-2012 were extracted from Swedish national register for retinopathy of prematurity, a web-based national register. Results During 2008-2012, 3488 infants with a gestational age (GA) at birth of <31 weeks had been screened for ROP in Sweden. Altogether, 30.3% (1057/3488) of the infants developed ROP and 5.2% (181/3488) were treated. Type 1 ROP was found in at least one eye in 83.2% (149/179) of the treated infants. One third of the eyes (32.2% right, 29.9% left eyes) were treated more than once. Laser was the only treatment in 90% of the eyes. Mean number of laser spots at first laser session was 1177 and 1386 in right and left eyes, respectively. Number of laser spots correlated negatively with GA at birth (p=0.01). There was no change in frequency of treatment or number of laser spots during the 5-year period. Anti-vascular endothelial growth factor injections were performed in 28 eyes, encircling band was used in five eyes and vitrectomies were performed in seven eyes. Twenty-six retinal surgeons performed 9.4 (range 1-37) treatment sessions in the 181 infants. Conclusions The present study reveals similar incidences of ROP and frequencies of treatment during the 5-year study period. Many surgeons were involved in treatment of a rather limited number of infants. The results call for national discussions on organisation of ROP treatment.

  • 16.
    Holmström, Gerd
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Oftalmiatrik.
    Larsson, Eva
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Oftalmiatrik.
    Development of Spherical Equivalent Refraction in Prematurely Born Children During the First 10 Years of Life: A Population-Based Study2005In: Arch Ophthalmol, Vol. 123, no 10, p. 1404-1411Article in journal (Refereed)
  • 17.
    Holmström, Gerd
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. oftalmiatrik.
    Larsson, Eva
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. oftalmiatrik.
    Long-term follow-up of visual functions in prematurely born children - a prospective population-based study up to 10 years of age.2008In: Journal of AAPOS, Vol. 12, no 2, p. 157-162Article in journal (Refereed)
  • 18.
    Holmström, Gerd
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Outcome of Retinopathy of Prematurity2013In: Clinics of Perinatology, ISSN 0095-5108, E-ISSN 1557-9840, Vol. 40, no 2, p. 311-321Article in journal (Refereed)
    Abstract [en]

    In prematurely born children, various visual and ophthalmologic sequelae occur because of both retinopathy of prematurity (ROP) and preterm birth per se. Several long-term follow-up studies have described the outcome of ROP. Visual impairment and blindness are well-known consequences, but the prevalence varies globally because of differing neonatal and ophthalmologic care. Improving treatment options and criteria for the treatment of ROP are continuously changing the ophthalmologic outcome. The anatomic outcome has improved with treatment, but good anatomic outcome in treated severe ROP does not always reflect the functional outcome. There is no consensus regarding long-term follow-up of prematurely born children.

  • 19.
    Holmström, Gerd
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ögonsjukdomar2011In: Pediatrik / [ed] Christian Moëll, Jan Gustafsson, Stockholm: Liber, 2011, 1, p. 527-535Chapter in book (Other academic)
  • 20.
    Holmström, Gerd
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Marie-Louise, Bondeson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Eriksson, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Åkerblom, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    'Congenital' nystagmus may hide various ophthalmic diagnoses2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 5, p. 412-416Article in journal (Refereed)
    Abstract [en]

    Purpose

    To investigate whether patients registered at a low-vision centre with ‘nystagmus’ had any underlying, but so far unknown, ophthalmic diagnosis.

    Methods

    All patients registered at the low-vision centre of Uppsala county with nystagmus as their major diagnosis were identified. Their medical records were studied to exclude those with other general diagnoses that could explain the nystagmus. The remaining group of patients underwent an ophthalmic examination, refraction and optical coherence tomography (OCT). Electroretinogram and genetic analyses were performed when indicated.

    Results

    Sixty-two patients with nystagmus as their main diagnosis were registered at the low-vision centre, Uppsala, and 43 of them had a major diagnosis other than nystagmus. Nystagmus was the major diagnosis in 19 patients, 15 of whom, aged 6–76 years, participated in the study. Two of the patients had foveal hypoplasia and albinism, four a seemingly isolated foveal hypoplasia, three achromatopsia, one rod-cone dystrophy, one degenerative high myopia, and two could not be evaluated. Only two patients appeared to have ‘congenital’ nystagmus. Eleven of the patients underwent a comprehensive genetic investigation of the PAX 6 gene. In addition, four of the patients were analysed for mutations in FOXC1 and PITX2 and one in FRMD7. No mutations were found in any of the patients analysed.

    Conclusion

    The study illustrates that many patients in our study group with nystagmus had underlying ophthalmic diagnoses. Early diagnosis is important to facilitate habilitation and to provide genetic counselling and, in the future, possibly also gene therapy.

  • 21.
    Holmström, Gerd
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Rydberg, Agneta
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Prevalence and Development of Strabismus in 10-Year-Old Premature Children: A population-based study2006In: Journal of pediatric ophthalmology and strabismus, ISSN 0191-3913, E-ISSN 1938-2405, Vol. 43, no 6, p. 346-352Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the prevalence and development of strabismus, at 10 years, in children born prematurely. Methods: This population-based study included 216 premature and 217 full-term children from the same geographic area. Results: Strabismus was noted in 16.2% (35 of 216) premature and in 3.2% (7 of 217) full-term children. The most important risk factors for strabismus at 10 years were anisometropia at 6 months, spherical equivalent refractive errors (ie, > +3 D or < -3 D) at 2.5 years, and various neurologic conditions. Conclusion: At 10 years, children born prematurely have a greater risk of strabismus than children born at term.

  • 22.
    Holmström, Gerd
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Tornqvist, Kristina
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Ophthalmol, Lund, Sweden..
    Al-Hawasi, Abbas
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Nilsson, Åsa
    Umea Univ, Dept Clin Sci, Ophthalmol, Umea, Sweden..
    Wallin, Agneta
    St Erik Eye Hosp, Stockholm, Sweden..
    Hellström, Ann
    Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Clin Neurosci & Rehabil,Sect Ophthalmol, Gothenburg, Sweden..
    Increased frequency of retinopathy of prematurity over the last decade and significant regional differences2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, no 2, p. 142-148Article in journal (Refereed)
    Abstract [en]

    Purpose: Retinopathy of prematurity (ROP) causes childhood blindness globally in prematurely born infants. Although increased levels of oxygen supply lead to increased survival and reduced frequency of cerebral palsy, increased incidence of ROP is reported.

    Methods: With the help of a Swedish register for ROP, SWEDROP, national and regional incidences of ROP and frequencies of treatment were evaluated from 2008 to 2015 (n=5734), as well as before and after targets of provided oxygen changed from 85-89% to 91-95% in 2014.

    Results: Retinopathy of prematurity (ROP) was found in 31.9% (1829/5734) of all infants with a gestational age (GA) of <31weeks at birth and 5.7% of the infants (329/5734) had been treated for ROP. Analyses of the national data revealed an increased incidence of ROP during the 8-year study period (p=0.003), but there was no significant increase in the frequency of treatment. There were significant differences between the seven health regions of Sweden, regarding both incidence of ROP and frequency of treatment (p<0.001). Comparison of regional data before and after the new oxygen targets revealed a significant increase in treated ROP in one region [OR: 2.24 (CI: 1.11-4.49), p=0.024] and a borderline increase in one other [OR: 3.08 (CI: 0.99-9.60), p=0.052].

    Conclusion: The Swedish national ROP register revealed an increased incidence of ROP during an 8-year period and significant regional differences regarding the incidence of ROP and frequency of treatment.

  • 23.
    Holmström, Gerd
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    van Wijngaarden, Peter
    Coster, Douglas J.
    Wiliams, Keryn A.
    Genetic susceptibility to retinopathy of prematurity: the evidence from clinical and experimental animal studies2007In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 91, no 12, p. 1704-1708Article, review/survey (Refereed)
    Abstract [en]

    Despite advances in management and treatment, retinopathy of prematurity remains a major cause of childhood blindness. Evidence for a genetic basis for susceptibility to retinopathy of prematurity is examined, including the influences of sex, ethnicity, and ocular pigmentation. The role of polymorphisms is explored in the genes for vascular endothelial growth factor and insulin-like growth factor-1, and of mutations in the Norrie disease gene. Insights into the genetic basis of retinopathy of prematurity provided by the animal model of oxygen induced retinopathy are examined. Evidence for a genetic component for susceptibility to retinopathy of prematurity is strong, although the molecular identity of the gene or genes involved remains uncertain.

  • 24.
    Hreinsdottir, Jonina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Brodd, Katarina Strand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ornkloo, H.
    Department of Psychology, Mid Sweden University, Östersund, Sweden.
    von Hofsten, Claes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ophthalmological outcome and visuospatial ability in very preterm children measured at 2.5 years corrected age2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 12, p. 1144-1149Article in journal (Refereed)
    Abstract [en]

    AimTo investigate the ophthalmological outcome of very preterm children at 2.5years corrected age (CA) and perform a test of visuospatial and cognitive abilities. MethodsA population-based, prospective study (LOVIS study) in Uppsala County, Sweden, comprised 111 very preterm children (<32 w gestational age [GA]) born between 1 January 2004 and 31 December 2007. Ophthalmic evaluations were undertaken in 98/109 children (89.9%) alive at 2.5 years. Spatial cognition was investigated with a test of five alternative blocks in 48 preterm and 25 term-born children. ResultsVisual impairment, strabismus or refractive errors, were found in 12% of the children. None of the children were blind in both eyes. Logistic regression analyses revealed significant associations between strabismus and periventricular leucomalacia/intraventricular haemorrhage (OR 9.6, p=0.025) and between refractive errors and severe retinopathy of prematurity (OR 9.8, p=0.011) and GA (OR 0.763, p=0.034). Oval and rectangular blocks were significantly more difficult to insert into a box for preterm than full-term children (p=0.048 and 0.013, respectively). There was a significant correlation between total scores for the five blocks and GA at birth (p=0.035). ConclusionEye and visual problems were found in 12% of the preterm children at 30months CA. Preterm children had difficulties with blocks of complex shapes.

  • 25.
    Hreinsdottir, Jonina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kaul, Ylva Fredriksson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Rosander, Kerstin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    von Hofsten, Claes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Impaired cognitive ability at 2.5 years predicts later visual and ophthalmological problems in children born very preterm2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 5, p. 822-830Article in journal (Refereed)
    Abstract [en]

    Aim: To identify possible predictive factors for visual problems at 6.5 years in children born very preterm.

    Methods: During 2004–2007, all very preterm infants (gestational age [GA] <32 weeks) in Uppsala County, Sweden were screened for retinopathy of prematurity (ROP) neonatally; at four months, visual tracking was tested; at 2.5 years, visuospatial and cognitive tests were carried out. At 6.5 years, 84 preterm children and a reference group of 64 full‐term children underwent ophthalmological testing.

    Results: Mean visual acuity (VA) did not differ between the groups, but subnormal VA (≤0.8) was more common in the preterm group (31% vs 14%; p < 0.05). More often than full‐term children, preterm children had impaired contrast sensitivity (<0.5) (36% vs 19%; p < 0.05) and strabismus (8% vs 0%; p < 0.05). Low GA, ROP, intraventricular haemorrhage 3‐4/periventricular leukomalacia and cognitive disability at 2.5 years predicted ophthalmological and visual problems at 6.5 years. Visual tracking ability at four months was not predictive of ophthalmological outcome.

    Conclusion: Children born preterm had more ophthalmological problems at 6.5 years of age, including subtle dysfunctions. ROP, early brain injury and impaired cognitive function around 2.5 years predicted later ophthalmological dysfunctions.

  • 26.
    Kaul, Ylva Fredriksson
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Rosander, Kerstin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Hofsten, von, Claes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Brodd, Katarina Strand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kaul, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Bohm, Birgitta
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Visual tracking in very preterm infants at 4 months predicts neurodevelopment at 3 years of age2016In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 80, no 1, p. 35-42Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Typically developing infants track moving objects with eye and head movements in a smooth and predictive way at 4 mo of age, but this ability is delayed in very preterm infants. We hypothesized that visual tracking ability in very preterm infants predicts later neurodevelopment. METHOD: In 67 very preterm infants (gestational age<32wk), eye and head movements were assessed at 4 mo corrected age while the infant tracked a moving object. Gaze gain, smooth pursuit, head movements, and timing of gaze relative the object were analyzed off line. Results of the five subscales included in the Bayley Scales of Infant Development (BSID-III) at 3 y of age were evaluated in relation to the visual tracking data and to perinatal risk factors. RESULTS: Significant correlations were obtained between gaze gain and cognition, receptive and expressive language, and fine motor function, respectively, also after controlling for gestational age, severe brain damage, retinopathy of prematurity, and bronchopulmonary dysplasia. CONCLUSION: This is the first study demonstrating that the basic ability to visually track a moving object at 4 mo robustly predicts neurodevelopment at 3 y of age in children born very preterm.

  • 27.
    Larsson, E
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Oftalmiatrik.
    Rydberg, A
    Holmström, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Oftalmiatrik.
    A population-based study of the refractive outcome in 10-year-old preterm and full-term children.2003In: Arch Ophthalmol, Vol. 121, p. 1430-1436Article in journal (Refereed)
  • 28.
    Larsson, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Development of Astigmatism and Anisometropia in Preterm Children During the First 10 Years of Life: A Population-Based Study2006In: Archives of ophthalmology (1960), ISSN 0003-9950, Vol. 124, no 11, p. 1608-1614Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the development of astigmatism and anisometropia to 10 years of age in preterm children, previously included in a population-based study on the incidence of retinopathy of prematurity.

    Methods: Cycloplegic retinoscopies were performed in 198 preterm children at 6 months, 2(1)/(2) years, and 10 years of age. We analyzed the development of astigmatism of 1 diopter (D) or more and anisometropia of 1 D or more.

    Results: The amount and prevalence of astigmatism declined between 6 months and 2(1)/(2) years of age and then remained stable. We found no difference in the course of astigmatism at different ages with regard to stage of retinopathy of prematurity. The amount of anisometropia increased, but its prevalence remained unchanged. Multiple regression analyses showed that astigmatism of 1 D or more at 2(1)/(2) years of age and cryotreated severe retinopathy of prematurity were risk factors for astigmatism at 10 years of age, and that anisometropia of 2 D or more at 2(1)/(2) years of age was a risk factor for anisometropia at 10 years of age.

    Conclusions: The development of astigmatism and anisometropia showed a similar course, regardless of stage of retinopathy of prematurity. The retinoscopy findings at 6 months of age were of no value in predicting astigmatism and anisometropia at 10 years of age, but the refraction at 2(1)/(2) years of age was. Retinoscopy at about 2(1)/(2) years of age in all preterm children may be useful for detecting astigmatism and anisometropia that will persist in children of school age.

  • 29.
    Larsson, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Rydberg, Agneta
    Karolinska Institutet.
    Ophthalmological findings in 10-year-old full-term children: a population-based study2015In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 2, p. 192-198Article in journal (Refereed)
    Abstract [en]

    Purpose

    To determine different ophthalmological parameters in 10-year-old, healthy, full-term children in Stockholm County, Sweden.

    Methods

    Two hundred and seventeen children were included in the study. Best-corrected distance and near visual acuities (VA) were measured using logMAR charts. Cycloplegic retinoscopy was performed, and spherical equivalent and astigmatism were determined. Examination of ocular movement and cover test for distance and near were performed. Stereopsis was assessed with the TNO test, and contrast sensitivity with the Vistech test. The Royal Air Force rule was used for assessing accommodation, and near point of convergence was measured with the Lang fixation stick. Ophthalmoscopy was performed through dilated pupils.

    Results

    Eighty-two per cent of the children had a distance VA of −0.1 logMAR (1.3 Snellen acuity) or better. None of the children were visually impaired [VA >0.6 logMAR (<0.3 Snellen acuity)]. Ninety-three per cent had a near VA of −0.1 logMAR (1.25 Snellen acuity) or better. Mean spherical equivalent was 0.6 D. Eight (3.6%) children had hypermetropia (≥+2 D), and 17 (7.8%) were myopic (≤−0.5 D). Nine (4.1%) children had an astigmatism ≥1 D, and two (0.9%) had anisometropia of ≥1 D. Manifest strabismus was found in seven (3.2%) children, five of whom had exotropia. Heterophoria for distance and/or near was found in 80.2% of the children. In children without manifest strabismus, stereopsis >60 seconds of arc was found in five (2.4%). Three (1.4%) of 215 children had contrast sensitivity below normal limits. Binocular median near point of accommodation was 14 D, and median near point of convergence 6 cm.

    Conclusion

    Knowledge of various visual functions in normally developing children is crucial to be able to draw conclusions from ophthalmological examinations in children with eye diseases. This population-based study describes different ophthalmological parameters in full-term ten-year-old children. The material can be used as a control when examining children of similar ages with various ophthalmological conditions, such as groups of children with specific neurological or retinal diseases, and syndromes.

  • 30.
    Larsson, Eva
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Oftalmiatrik.
    Rydberg, Agneta
    Holmström, Gerd
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Oftalmiatrik.
    A Population-Based Study on the Visual Outcome in 10-Year-Old Preterm and Full-Term Children2005In: Arch Ophthalmol, Vol. 123, p. 825-832Article in journal (Refereed)
  • 31.
    Larsson, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Rydberg, Agneta
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Accommodation and convergence in 10-year-old prematurely born and full-term children: a population-based study2012In: Strabismus, ISSN 0927-3972, E-ISSN 1744-5132, Vol. 20, no 3, p. 127-132Article in journal (Refereed)
    Abstract [en]

    Purpose: To examine the accommodative amplitude and convergence in 10-year-old prematurely born children previously screened for retinopathy of prematurity (ROP) and to compare with full-term controls of the same age.

    Methods: Two-hundred and thirteen prematurely born and 217 children born at term were included. Accommodative amplitude and near-point convergence were assessed, together with best-corrected visual acuity (VA). A questionnaire was answered regarding possible problems at school.

    Results: Binocular accommodation (P = 0.03) and convergence (P = 0.003) were significantly poorer in prematurely born children. Accommodation was correlated to neurological findings in the preterm group, but not to the degree of prematurity or stage of ROP. Regarding convergence there were no correlations to neurology, stage of ROP, or degree of prematurity. For neither accommodation nor convergence were any correlations with distance and near VA found. Preterm children had a higher prevalence of school problems, and there was an association with poor accommodation.

    Conclusions: Prematurely born children had poorer accommodation and convergence than full-term children, but no association with near VA was found. The reduction of accommodative amplitude and convergence was small and was probably of little clinical significance. However, it may have additional effects on other ophthalmological problems and school problems in the preterm group.

  • 32.
    Larsson, Eva
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Oftalmiatrik.
    Rydberg, Agneta
    Holmström, Gerd
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Oftalmiatrik.
    Contrast sensitivity in 10 year old preterm and full term children: a population based study2006In: Br J Ophthalmol, Vol. 90, p. 87-90Article in journal (Refereed)
  • 33.
    Lundgren, P.
    et al.
    Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden..
    Lundberg, L.
    Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden..
    Hellgren, G.
    Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden..
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Hard, A. L.
    Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden..
    Smith, L. E.
    Harvard Med Sch, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA USA..
    Wallin, A.
    St Erik Eye Hosp, Stockholm, Sweden..
    Hallberg, B.
    Karolinska Inst, Stockholm, Sweden.;Univ Hosp, Dept Neonatol, Stockholm, Sweden..
    Hellstrom, A.
    Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden..
    Aggressive posterior retinopathy of prematurity is associated with multiple infectious episodes and thrombocytopenia2016In: European Journal of Pediatrics, ISSN 0340-6199, E-ISSN 1432-1076, Vol. 175, no 11, p. 1842-1842Article in journal (Refereed)
  • 34. Lundgren, Pia
    et al.
    Kistner, Anna
    Andersson, Eva M.
    Pupp, Ingrid Hansen
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ley, David
    Niklasson, Aimon
    Smith, Lois E. H.
    Wu, Carolyn
    Hellstrom, Ann
    Lofqvist, Chatarina
    Low Birth Weight Is a Risk Factor for Severe Retinopathy of Prematurity Depending on Gestational Age2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 10, p. e109460-Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate the impact of low birth weight as a risk factor for retinopathy of prematurity (ROP) that will require treatment in correlation with gestational age at birth (GA). Study design: In total, 2941 infants born <32 weeks GA were eligible from five cohorts of preterm infants previously collected for analysis in WINROP (Weight IGF-I Neonatal ROP) from the following locations: Sweden (EXPRESS) (n = 426), North America (n = 1772), Boston (n = 338), Lund (n = 52), and Gothenburg (n = 353). Data regarding GA at birth, birth weight (BW), gender, and need for ROP treatment were retrieved. Birth weight standard deviation scores (BWSDS) were calculated with Swedish as well as Canadian reference models. Small for gestational age (SGA) was defined as BWSDS less than -2.0 SDS using the Swedish reference and as BW below the 10 th percentile using the Canadian reference charts. Results: Univariate analysis showed that low GA (p<0.001), low BW (p<0.001), male gender (p<0.05), low BWSDSCanada (p<0.001), and SGACanada (p<0.01) were risk factors for ROP that will require treatment. In multivariable logistic regression analysis, low GA (p<0.0001), male gender (p<0.01 and p<0.05), and an interaction term of BWSDS*GA group (p<0.001), regardless of reference chart, were risk factors. Low BWSDS was less important as a risk factor in infants born at GA <26 weeks compared with infants born at GA >= 26 weeks calculated with both reference charts (BWSDSSweden, OR = 0.80 vs 0.56; and BWSDSCanada, OR = 0.72 vs 0.41). Conclusions: Low BWSDS as a risk factor for vision-threatening ROP is dependent on the infant's degree of immaturity. In more mature infants (GA >= 26 weeks), low BWSDS becomes a major risk factor for developing ROP that will require treatment. These results persist even when calculating BW deficit with different well-established approaches.

  • 35. Lundgren, Pia
    et al.
    Sjostrom, Elisabeth Stoltz
    Domellof, Magnus
    Kallen, Karin
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Hard, Anna-Lena
    Smith, Lois E.
    Lofqvist, Chatarina
    Hellstrom, Ann
    WINROP Identifies Severe Retinopathy of Prematurity at an Early Stage in a Nation-Based Cohort of Extremely Preterm Infants2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, p. e73256-Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate the ability of a postnatal weight-gain algorithm (WINROP) to identify sight-threatening retinopathy of prematurity (ROP type 1) in a nation-based extremely preterm infant cohort. Methods: This study enrolled all 707 live-born extremely preterm (gestational age [GA] <27 weeks) infants, born 2004-2007 in Sweden; the Extremely preterm Infants in Sweden Study (EXPRESS). WINROP analysis was performed retrospectively in 407 of the infants using weekly weight gain to assess the preterm infant's risk of developing ROP type 1 requiring treatment. GA, birthweight (BW), and weekly postnatal weight measurements were entered into WINROP. WINROP signals with an alarm to indicate if the preterm infant is at risk for ROP type 1. Results: In this extremely preterm population, WINROP correctly identified 96% (45/47) of the infants who required treatment for ROP type 1. The median time from alarm to treatment was 9 weeks (range, 4-20 weeks). Conclusions: WINROP, an online surveillance system using weekly weight gain, identified extremely preterm infants at risk for ROP type 1 requiring treatment at an early stage and with high sensitivity in a Swedish nation-based cohort.

  • 36. Löfqvist, Chatarina
    et al.
    Engström, Eva
    Sigurdsson, Jon
    Hård, Anna-Lena
    Niklasson, Aimon
    Ewald, Uwe
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Holmström, Gerd
    Department of Neuroscience.
    Smith, Lois E H
    Hellström, Ann
    Postnatal head growth deficit among premature infants parallels retinopathy of prematurity and insulin-like growth factor-1 deficit.2006In: Pediatrics, ISSN 1098-4275, Vol. 117, no 6, p. 1930-8Article in journal (Refereed)
  • 37.
    Molnar, Anna E. C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Andreasson, Sten O. L.
    Lund Univ, Dept Ophthalmol, Lund, Sweden..
    Larsson, Eva K. B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology. Uppsala Univ, Dept Neurosci, Ophthalmol, Uppsala, Sweden..
    Åkerblom, Hanna M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Holmström, Gerd E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Macular function measured by binocular mfERG and compared with macular structure in healthy children2015In: Documenta Ophthalmologica, ISSN 0012-4486, E-ISSN 1573-2622, Vol. 131, no 3, p. 169-176Article in journal (Refereed)
    Abstract [en]

    To create normative data in children from binocular multifocal ERG (mfERG) recordings and compare results with the macular thickness. Forty-nine 5- to 15-year-old healthy, full-term children were examined with Espion Multifocal System, using DTL electrodes. The stimulus matrix consisted of 37 hexagonal elements. Amplitudes, implicit times and response densities (presented in three rings) of the first-order component P1 were analyzed. Measurements of macular thickness were performed with spectral-domain Cirrus OCT. There were no significant differences between right and left eyes regarding mfERG recordings. Median P1 implicit times of Rings 1-3 of the 46 right eyes were 30.0, 30.0 and 30.8 ms and response densities 20.5, 10.9 and 7.6 nV/deg(2), respectively. Implicit time was longer in boys than in girls (p = 0.009, 0.039, 0.005 in Rings 1-3) and was correlated with age (r (s) = 0.417, 0.316, 0.274 in Rings 1-3). Implicit time in Ring 1 correlated significantly with the inner circle of the OCT measurements (p = 0.014). Binocular mfERG with DTL electrodes is a reliable test of the central macular function in children and correlates with macular structure. As previously not shown, there was a significant difference in implicit time between boys and girls.

  • 38.
    Molnar, Anna E. C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Andreasson, Sten O.
    Lund Univ, Dept Ophthalmol, Lund, Sweden..
    Larsson, Eva K. B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Åkerblom, Hanna M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology. Uppsala Univ, Dept Neurosci Ophthalmol, S-75185 Uppsala, Sweden..
    Holmström, Gerd E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Reduction of Rod and Cone Function in 6.5-Year-Old Children Born Extremely Preterm2017In: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 135, no 8, p. 854-861Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The function of rods and cones in children born extremely preterm has not yet been fully investigated. OBJECTIVE To compare retinal function via full-field electroretinographic (ffERG) recordings in 6.5-year-old children born extremely preterm with children born at term. DESIGN, SETTING, AND PARTICIPANTS A subcohort study was conducted from July 1, 2010, to January 15, 2014, of the national Extremely Preterm Infants in Sweden Study, including preterm children (< 27 weeks' gestational age) and children born at term, at 6.5 years of age and living in the Uppsala health care region in Sweden. Full-field electroretinography was performed binocularly, using DTL electrodes and electroretinographic (ERG) protocols with flash strengths of 0.009, 0.17, 3.0, and 12.0 candelas (cd)/s/m(2), together with 30-Hz flicker and 3.0 cd/s/m(2) single-cone flash. MAIN OUTCOMES AND MEASURES The ffERG recordings were analyzed, and their associations with gestational age and retinopathy of prematurity were examined. RESULTS Adequate ffERG recordings were obtained from 52 preterm children (19 girls and 33 boys; mean [SD] age at examination, 6.6 [0.1] years) and 45 children born at term (22 girls and 23 boys; mean [SD] age at examination, 6.6 [0.1] years). Lower amplitudes of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 3.0 cd/s/m(2): mean difference, -48.9 mu V [95% CI, -80.0 to -17.9 mu V]; P =. 003; the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m(2): mean difference, -55.7 mu V [95% CI, -92.5 to -18.8 mu V]; P = .004), as well as of the isolated cone response (30-Hz flicker ERG: mean difference, -12.1 mu V [95% CI, -22.5 to -1.6 mu V]; P = .03), were found in the preterm group in comparison with the group born at term. The implicit time of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m(2)) was longer (mean difference, 1.2 milliseconds [95% CI, 0.3-2.0 milliseconds]; P = .01) in the preterm group, as were the isolated cone responses (30-Hz flicker ERG: mean difference, 1.2 milliseconds [95% CI, 0.5-1.8 milliseconds]; P < .001), than in the group born at term. No association was found between the ffERG recordings and gestational age or retinopathy of prematurity in the preterm group. CONCLUSIONS AND RELEVANCE Both rod function and cone function were reduced in children born extremely preterm when compared with children born at term. There was no association with retinopathy of prematurity in the preterm group, which suggests that being born extremely preterm may be one of the main reasons for a general retinal dysfunction.

  • 39.
    Molnar, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Holmstrom, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Macular thickness assessed with spectral domain OCT in a population-based study of children: normative data, repeatability and reproducibility and comparison with time domain OCT2015In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 5, p. 470-475Article in journal (Refereed)
    Abstract [en]

    PurposeTo collect data on macular thickness assessed with Cirrus OCT in healthy children in a population-based study, to examine the repeatability and reproducibility, and to compare the values with Stratus OCT. MethodsFifty-eight 6- to 15-year-old children, born at term, were examined. Best-corrected visual acuity and refraction were assessed. One examiner performed three OCT assessments, and the repeatability was calculated. Thereafter, a second examiner repeated the examinations to calculate the reproducibility. One eye was randomized to be included in the normal material. Finally, the second examiner assessed the macular thickness with the Stratus OCT. ResultsThe mean value (SD) of central macular thickness was 255 +/- 17m, and the total macular volume was 10.3 +/- 0.5mm(3). No correlations were found between macular thickness and age, gender or refraction. The coefficients of variance (CoVs) for both repeatability and reproducibility were <1.21%, and the intraclass correlations (ICCs) were over 0.86. The Cirrus OCT showed a 29% thicker central macular thickness than the Stratus OCT. ConclusionNormal values for macular thickness assessed with Cirrus OCT in healthy full-term children in a population-based study were reported. The assessments showed high repeatability and reproducibility. The values of Cirrus and Stratus OCT differed and the techniques were not interchangeable.

  • 40.
    Molnar, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Rosén, Rebecka M.
    Department of Clinical Neuroscience, Karolinska Institutet.
    Nilsson, Maria
    Department of Clinical Neuroscience, Karolinska Institutet.
    Larsson, Eva K B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Holmström, Gerd
    Department of Clinical Neuroscience, Astrid Lindgren Children ’ s Hospital, Karolinska Institutet, Stockholm, Sweden.
    Hellgren, Kerstin M.
    Department of Clinical Neuroscience, Karolinska Institutet.
    Central macular thickness in 6.5-year-old children born extremely preterm is strongly associated with gestational age even when adjusted for risk factors2017In: Retina, ISSN 0275-004X, E-ISSN 1539-2864, Vol. 37, no 12, p. 2281-2288Article in journal (Refereed)
    Abstract [en]

    Purpose:To assess the macular thickness in 6.5-year-old children born extremelypreterm (EPT) in comparison with children born at term and to investigate risk factorsassociated with the macular thickness in the preterm group.

    Methods:A population-based study of 6.5-year-old children born before the gestationalage of 27 weeks and age-matched control subjects. Macular assessments with opticalcoherence tomography were performed, and the results were compared with neonatal riskfactors and sex.

    Results:Adequate optical coherence tomography measurements were obtained from134 children born EPT (mean gestational age of 25 weeks [range 23–26]) and 145 controlsubjects. The mean (range) of central macula thickness was significantly increased (P,0.001)in the EPT group (right eyes: 282mm [238–356], left eyes: 283mm[229–351]), compared withthe control group (right eyes: 249mm [208–293], left eyes: 248mm[207–290]). A multiple linearmixed model analysis of the EPT group revealed gestational age, retinopathy of prematurity,and male gender as important risk factors for an increased macular thickness. The macularthickness decreased by 3.9mm per gestational week, when adjusted for retinopathy of pre-maturity and sex.

    Conclusion:Extremely preterm birth constitutes a substantial risk factor for a thickcentral macula, even when adjusted for retinopathy of prematurity and male gender.

  • 41.
    Nyström, Anna-Maja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Ekvall, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Thuresson, Ann-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Annerén, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Bondeson, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    A severe form of Noonan syndrome and autosomal dominant café-au-lait spots: evidence for different genetic origins2009In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 98, no 4, p. 693-698Article in journal (Refereed)
    Abstract [en]

    Aim: The clinical overlap among Noonan syndrome (NS), cardio-facio-cutaneous (CFC), LEOPARD and Costello syndromes as well as Neurofibromatosis type 1 is extensive, which complicates the process of diagnosis. Further genotype–phenotype correlations are required to facilitate future diagnosis of these patients. Therefore, investigations of the genetic cause of a severe phenotype in a patient with NS and the presence of multiple café-au-lait spots (CAL) spots in the patient and four members of the family were performed. Methods: Mutation analyses of candidate genes, PTPN11, NF1, SPRED1 and SPRED2, associated with these syndromes, were conducted using DNA sequencing. Results: A previously identified de novo mutation, PTPN11 F285L and an inherited NF1 R1809C substitution in the index patient were found. However, neither PTPN11 F285L, NF1 R1809C, SPRED1 nor SPRED2 segregated with CAL spots in the family. The results indicate that the familial CAL spots trait in this family is caused by a mutation in another gene, distinct from previous genes associated with CAL spots in these syndromes. Conclusion: We suggest that the atypical severe symptoms in the index patient may be caused by an additive effect on the F285L mutation in PTPN11 by another mutation, for example the NF1 R1809C or alternatively, the not yet identified gene mutation associated with CAL spots in this family.

  • 42.
    Serenius, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kallen, Karin
    Blennow, Mats
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Fellman, Vineta
    Holmstrom, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Lindberg, Eva
    Lundqvist, Pia
    Marsal, Karel
    Norman, Mikael
    Olhager, Elisabeth
    Stigson, Lennart
    Stjernqvist, Karin
    Vollmer, Brigitte
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Neurodevelopmental Outcome in Extremely Preterm Infants at 2.5 Years After Active Perinatal Care in Sweden EDITORIAL COMMENT2013In: Obstetrical and Gynecological Survey, ISSN 0029-7828, E-ISSN 1533-9866, Vol. 68, no 12, p. 781-783Article in journal (Other academic)
  • 43.
    Serenius, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Källén, Karin
    Centre of Reproductive Epidemiology, Lund University, Sweden.
    Blennow, Mats
    Departments of Clinical Science, Intervention, and Technology, Karolinska Institutet, Sweden.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Fellman, Vineta
    Departments of Pediatrics, Clinical Sciences Lund, Lund University, Sweden.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Lindberg, Eva
    Department of Pediatrics, Örebro University, Sweden.
    Lundqvist, Pia
    Departments of Pediatrics, Health Sciences, Lund University, Sweden.
    Maršál, Karel
    Departments of Obstetrics and Gynecology, Clinical Sciences Lund, Lund University, Sweden.
    Norman, Mikael
    Departments of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
    Olhager, Elisabeth
    Department of Clinical and Experimental Medicine, Linköping University, Sweden.
    Stigson, Lennart
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Sweden.
    Stjernqvist, Karin
    Psychology, Lund University, Sweden.
    Vollmer, Brigitte
    Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Neurodevelopmental outcome in extremely preterm infants at 2.5 years after active perinatal care in Sweden2013In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 309, no 17, p. 1810-1820Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Active perinatal care increases survival of extremely preterm infants; however, improved survival might be associated with increased disability among survivors.

    OBJECTIVE: To determine neurodevelopmental outcome in extremely preterm children at 2.5 years (corrected age).

    DESIGN, SETTING, AND PARTICIPANTS: Population-based prospective cohort of consecutive extremely preterm infants born before 27 weeks of gestation in Sweden between 2004 and 2007. Of 707 live-born infants, 491 (69%) survived to 2.5 years. Survivors were assessed and compared with singleton control infants who were born at term and matched by sex, ethnicity, and municipality. Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences. MAIN OUTCOMES AND MEASURES: Cognitive, language, and motor development was assessed with Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-lll), which are standardized to mean (SD) scores of 100 (15). Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments. Assessments were made by week of gestational age.

    RESULTS: At a median age of 30.5 months (corrected), 456 of 491 (94%) extremely preterm children were evaluated (41 by chart review only). For controls, 701 had information on health status and 366 had Bayley-lll assessments. Mean (SD) composite Bayley-III scores (cognition, 94 [12.3]; language, 98 [16.5]; motor, 94 [15.9]) were lower than the corresponding mean scores for controls (cognition, 104 [10.6]; P < .001; adjusted difference in mean scores, 9.2 [99% CI, 6.9-11.5]; language, 109 [12.3]; P < .001; adjusted difference in mean scores, 9.3 [99% Cl, 6.4-12.3]; and motor, 107 [13.7]; P < .001; adjusted difference in mean scores, 12.6 [99% Cl, 9.5-15.6]). Cognitive disability was moderate in 5% of the extremely preterm group vs 0.3% in controls (P < .001) and it was severe in 6.3% of the extremely preterm group vs 0.3% in controls (P < .001). Language disability was moderate in 9.4% of the extremely preterm group vs 2.5% in controls (P < .001) and severe in 6.6% of the extremely preterm group vs 0% in controls (P < .001). Other comparisons between the extremely preterm group vs controls were for cerebral palsy (7.0% vs 0.1%; P < .001), for blindness (0.9% vs 0%; P = .02), and for hearing impairment (moderate and severe, 0.9% vs 0%; P = .02, respectively). Overall, 42% (99% CI, 36%-48%) of extremely preterm children had no disability, 31% (99% CI, 25%-36%) had mild disability, 16% (99% CI, 12%-21%) had moderate disability, and 11% (99% CI, 7.2%-15%) had severe disability. Moderate or severe overall disability decreased with gestational age at birth (22 weeks, 60%; 23 weeks, 51%; 24 weeks, 34%; 25 weeks, 27%; and 26 weeks, 17%; P for trend < .001).

    CONCLUSIONS AND RELEVANCE: Of children born extremely preterm and receiving active perinatal care, 73% had mild or no disability and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling families facing extremely preterm birth.

  • 44.
    Serenius, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Sjörs, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Blennow, Mats
    Department of Pediatrics, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Fellman, Vineta
    Department of Pediatrics, Lund University, Sweden.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Maršál, Karel
    Department of Obstetrics and Gynecology, Lund University, Sweden.
    Lindberg, Eva
    Department of Pediatrics, Örebro University, Sweden.
    Olhager, Elisabeth
    Department of Pediatrics, Linköping University, Sweden.
    Stigson, Lennart
    Department of Pediatrics, Sahlgrenska University Hospital, Göteborg, Sweden.
    Westgren, Magnus
    Department of Obstetrics and Gynecology, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Källen, Karin
    Centre for Reproductive Epidemiology, Lund University, Sweden.
    EXPRESS study shows significant regional differences in 1-year outcome of extremely preterm infants in Sweden2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 1, p. 27-37Article in journal (Refereed)
    Abstract [en]

    AIM: The aim of this study was to investigate differences in mortality up to 1 year of age in extremely preterm infants (before 27 weeks) born in seven Swedish healthcare regions.

    METHODS: National prospective observational study of consecutively born, extremely preterm infants in Sweden 2004-2007. Mortality was compared between regions. Crude and adjusted odds ratios and 95% CI were calculated.

    RESULTS: Among 844 foetuses alive at mother's admission for delivery, regional differences were identified in perinatal mortality for the total group (22-26 weeks) and in the stillbirth and perinatal and 365-day mortality rates for the subgroup born at 22-24 weeks. Among 707 infants born alive, regional differences were found both in mortality before 12 h and in the 365-day mortality rate for the subgroup (22-24 weeks) and for the total group (22-26 weeks). The mortality rates were consistently lower in two healthcare regions. There were no differences in the 365-day mortality rate for infants alive at 12 h or for infants born at 25 weeks. Neonatal morbidity rates among survivors were not higher in regions with better survival rates. Perinatal practices varied between regions.

    CONCLUSION: Mortality rates in extremely preterm infants varied considerably between Swedish healthcare regions in the first year after birth, particularly between the most immature infants.

  • 45.
    Spandau, Ulrich
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Tomic, Zoran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Åkerblom, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Time to consider a new treatment protocol for aggressive posterior retinopathy of prematurity?2013In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 91, no 2, p. 170-175Article in journal (Refereed)
    Abstract [en]

    Purpose: 

    To discuss treatment modalities for aggressive posterior retinopathy of prematurity (AP-ROP).

    Methods: 

    The medical charts of all infants with AP-ROP at Uppsala University Hospital, Sweden, during a 2-year period (2009 and 2010) were reviewed. Eight infants (16 eyes) with a mean gestational age of 23.8 weeks and a mean birth weight of 592 g were treated with laser and/or intravitreal injections of bevacizumab (0.4 and 0.625 mg). RetCam photography was used to document the retinal appearance before and after treatment.

    Results: 

    All infants (16 eyes) had AP-ROP in zone I. Mean time at initial treatment was 34 weeks postmenstrual age. Two eyes (one infant) were only treated with laser, and six eyes (three infants) were treated with laser therapy or cryopexy and, because of lack of regression, with bevacizumab as salvage therapy. Eight eyes (four infants) were treated with a first-line bevacizumab injection and four of these eyes (two infants) with additional laser ablation for continued disease progression in zone II. Macular dragging occurred in one eye of one infant primarily treated with laser.

    Conclusions: 

    Given the high complication rate of the extensive laser treatment for zone I ROP, it is worth considering anti-vascular endothelial growth factor treatment as an alternative therapy. Further knowledge concerning side effects and long-term ocular and systemic outcome is warranted before this drug becomes general clinical practice.

  • 46.
    Stoltz Sjöström, Elisabeth
    et al.
    Department of Clinical Sciences, Paediatrics, Umeå University, Umeå, Sweden.
    Lundgren, Pia
    Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Öhlund, Inger
    Department of Clinical Sciences, Paediatrics, Umeå University, Umeå, Sweden.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Hellström, Ann
    Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Domellöf, Magnus
    Low energy intake during the first 4 weeks of life increases the risk for severe retinopathy of prematurity in extremely preterm infants.2016In: Archives of Disease in Childhood: Fetal and Neonatal Edition, ISSN 1359-2998, E-ISSN 1468-2052, Vol. 101, no 2, p. F108-F113Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Poor weight gain during the first weeks of life in preterm infants is closely associated with the risk of developing the retinopathy of prematurity (ROP) and insufficient nutrition might be an important contributing factor. This study aimed to evaluate the effect of energy and macronutrient intakes during the first 4 weeks of life on the risk for severe ROP (stages 3-5).

    STUDY DESIGN: A population-based study including all Swedish extremely preterm infants born before 27 gestational weeks during a 3-year period. Each infant was classified according to the maximum stage of ROP in either eye as assessed prospectively until full retinal vascularisation. The detailed daily data of actual intakes of enteral and parenteral nutrition and growth data were obtained from hospital records.

    RESULTS: Of the included 498 infants, 172 (34.5%) had severe ROP and 96 (19.3%) were treated. Energy and macronutrient intakes were less than recommended and the infants showed severe postnatal growth failure. Higher intakes of energy, fat and carbohydrates, but not protein, were significantly associated with a lower risk of severe ROP. Adjusting for morbidity, an increased energy intake of 10 kcal/kg/day was associated with a 24% decrease in severe ROP.

    CONCLUSIONS: We showed that low energy intake during the first 4 weeks of life was an independent risk factor for severe ROP. This implies that the provision of adequate energy from parenteral and enteral sources during the first 4 weeks of life may be an effective method for reducing the risk of severe ROP in extremely preterm infants.

  • 47. Storm, Tina
    et al.
    Tranebjærg, Lisbeth
    Frykholm, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Birn, Henrik
    Verroust, Pierre J
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundelin, Birgitta
    Hertz, Jens Michael
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ericson, Katharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Christensen, Erik I
    Nielsen, Rikke
    Renal phenotypic investigations of megalin-deficient patients: novel insights into tubular proteinuria and albumin filtration2013In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 28, no 3, p. 585-591Article in journal (Refereed)
    Abstract [en]

    Background

    The reabsorption of filtered plasma proteins, hormones and vitamins by the renal proximal tubules is vital for body homeostasis. Studies of megalin-deficient mice suggest that the large multi-ligand endocytic receptor megalin plays an essential role in this process. In humans, dysfunctional megalin causes the extremely rare Donnai-Barrow/Facio-Oculo-Acustico-Renal (DB/FOAR) syndrome characterized by a characteristic and multifaceted phenotype including low-molecular-weight proteinuria. In this study, we examined the role of megalin for tubular protein reabsorption in humans through analysis of proximal tubular function in megalin-deficient patients.

    Methods

    Direct sequencing of the megalin-encoding gene (LRP2) was performed in a family in which three children presented with classical DB/FOAR manifestations. Renal consequences of megalin deficiency were investigated through immunohistochemical analyses of renal biopsy material and immunoblotting of urine samples.

    Results

    In the patients, a characteristic urinary protein profile with increased urinary excretion of vitamin D-binding protein, retinol-binding protein and albumin was associated with absence of, or reduced, proximal tubular endocytic uptake as shown by renal immunohistochemistry. In the absence of tubular uptake, urinary albumin excretion was in the micro-albuminuric range suggesting that limited amounts of albumin are filtered in human glomeruli.

    Conclusions

    This study demonstrated that megalin plays an essential role for human proximal tubular protein reabsorption and suggests that only limited amounts of albumin is normally filtered in the human glomeruli. Finally, we propose that the characteristic urinary protein profile of DB/FOAR patients may be utilized as a diagnostic marker of megalin dysfunction.

  • 48. Vinnars, Marie-Therese
    et al.
    Nasiell, Josefine
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Norman, Mikael
    Westgren, Magnus
    Papadogiannakis, Nikos
    Association between placental pathology and neonatal outcome in preeclampsia: a large cohort study2014In: Hypertension in Pregnancy, ISSN 1064-1955, E-ISSN 1525-6065, Vol. 33, no 2, p. 145-158Article in journal (Refereed)
    Abstract [en]

    Objective: To study associations between placental histopathology and neonatal outcome in preeclampsia (PE). Study design: The cohort consisted of 544 singleton pregnancies complicated by PE and managed at Karolinska University Hospital, Stockholm, Sweden during 2000-2009. Evaluation of placental histopathology was made by one senior perinatal pathologist, blinded to outcome. Clinical outcome was obtained from prospectively collected medical registry data and medical records. Main outcome measures were intrauterine fetal death, smallness for gestational age, admission to neonatal unit, major neonatal morbidity (defined as presence of intraventricular hemorrhage >= grade 3, retinopathy of prematurity >= grade 3, necrotizing enterocolitis, cystic periventricular leucomalacia and/or severe bronchopulmonary dysplasia) and neonatal mortality. Logistic regression analyses including gestational age were performed. Results: Abnormal placental weight, both low (adjusted odds ratio (OR) [95% confidence interval] 5.2 [1.1-24], p = 0.03) and high (adjusted OR 1048 [21-51 663], p < 0.001) for gestational age, was associated with major neonatal morbidity in preterm infants. Accelerated villous maturation was less prevalent in intrauterine fetal death pregnancies (adjusted OR 0.18 [0.04-0.77], p = 0.02). Decidual arteriopathy increased the odds for admission to neonatal care (adjusted OR 2.7 [1.1-6.5], p = 0.03). Infarction involving >= 5% of the placenta was associated with intrauterine fetal death and small for gestational age infants (adjusted OR's 75 [5.5-1011], p = 0.001 and 3.2 [1.7-5.9], p < 0.001; respectively). No relations between histological variables and neonatal mortality could be found. Conclusion: Placental pathology in PE reflects adverse perinatal events and deviant placental weight predicts adverse neonatal outcome in preeclamptic women delivering preterm. Placental investigation without delay can contribute to neonatal risk assessment.

  • 49. Vinnars, Marie-Therese
    et al.
    Papadogiannakis, Nikos
    Nasiell, Josefine
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Westgren, Magnus
    Placental pathology in relation to stillbirth and neonatal outcome in an extremely preterm population: a prospective cohort study2015In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 94, no 6, p. 584-590Article in journal (Refereed)
    Abstract [en]

    Objective: To study associations between placental histopathology and stillbirth as well as neonatal outcome in a population born extremely preterm. Design: Prospective cohort study. Setting: Stockholm, Sweden. Population: 167 infants born <27 gestational weeks during 2004-2007. Methods: One senior perinatal pathologist, blinded to outcome data, evaluated all placental slides. Main outcome measures: Intrauterine fetal death, small-for-gestational age, major neonatal morbidity (intraventricular hemorrhage grade 3, retinopathy of prematurity grade 3, necrotizing enterocolitis, cystic periventricular leukomalacia or severe bronchopulmonary dysplasia) and neonatal mortality. Additional outcome variables were Apgar score at 5min, sepsis, and treated patent ductus arteriosus. Results: Accelerated villous maturation was associated with a decreased risk for Apgar score <7 at 5min (p=0.041). Fetal thrombosis and low placental weight were associated with an increased risk for both intrauterine fetal death (p<0.001 and p=0.011, respectively) and small-for-gestational age (p<0.001 and p<0.001, respectively). Conclusion: Placental histology may have prognostic value as it appears to be associated with intrauterine fetal death, as well as with being small-for-gestational age and assignment of a low Apgar score at birth.

  • 50.
    Åkerblom, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Andreasson, Sten
    Univ Lund Hosp, Dept Ophthalmol, S-22185 Lund, Sweden..
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Macular function in preterm children at school age2016In: Documenta Ophthalmologica, ISSN 0012-4486, E-ISSN 1573-2622, Vol. 133, no 3, p. 151-157Article in journal (Refereed)
    Abstract [en]

    Macular development is a complex process that starts by mid-gestation and continues several years after birth. A preterm birth could affect this development, causing increased thickness in the central macula, but the effect of the macular function remains uncertain. The aim of this study was to investigate the macular function measured with multifocal electroretinography (mfERG), in former preterm children and compare with healthy controls. A second aim was to correlate central macular function with central macular thickness measured with optical coherent tomography (OCT), in the preterm group. Fifteen former preterm children born before 32 weeks of gestation were included in the study. MfERG results from 12 children acted as controls. Visual acuity, refraction in cycloplegia and mfERG were carried out in all children, and optical coherent tomography (OCT) was performed in the preterm children. Main outcomes were P1 amplitudes and implicit times for Rings 1-5 and "sum of groups" of the mfERG, and central macula thickness in area A1 measured with OCT. The P1 amplitudes were reduced in Rings 1-5 and "Sum of groups" in the preterm children compared to controls. There were no significant correlation between P1 amplitude or implicit times in Ring 1 and central macular thickness in the preterm group. Macular function is reduced in former preterm children compared to children born at term. This suggests that the structural changes with a thicker central retina can have an effect on function and may be one, of probably several, explanations for visual dysfunction in preterm children at school age.

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