| 1. |
- Lundgren, Pia, 1967, et al.
(författare)
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National cohort of infants born before 24 gestational weeks showed increased survival rates but no improvement in neonatal morbidity
- 2022
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:8, s. 1515-1525
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Tidskriftsartikel (refereegranskat)abstract
- Aim To describe survival and neonatal morbidities in infants born before 24 weeks of gestation during a 12-year period. Methods Data were retrieved from national registries and validated in medical files of infants born before 24 weeks of gestation 2007-2018 in Sweden. Temporal changes were evaluated. Results In 2007-2018, 282 live births were recorded at 22 weeks and 460 at 23 weeks of gestation. Survival to discharge from hospital of infants born alive at 22 and 23 weeks increased from 20% to 38% (p = 0.006) and from 45% to 67% (p < 0.001) respectively. Caesarean section increased from 12% to 22% (p = 0.038) for infants born at 22 weeks. Neonatal morbidity rates in infants alive at 40 weeks of postmenstrual age (n = 399) were unchanged except for an increase in necrotising enterocolitis from 0 to 33% (p = 0.017) in infants born at 22 weeks of gestation. Bronchopulmonary dysplasia was more common in boys than girls, 90% versus 82% (p = 0.044). The number of infants surviving to 40 weeks doubled over time. Conclusion Increased survival of infants born before 24 weeks of gestation resulted in increasing numbers of very immature infants with severe neonatal morbidities likely to have a negative impact on long-term outcome.
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| 2. |
- Morsing, Eva, et al.
(författare)
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[Survival and prematurity-related neonatal diagnoses among children born before 24 gestational weeks in Sweden 2007-2018]. : Allt fler barn födda före vecka 24 överlever, men sjukligheten är hög.
- 2023
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Ingår i: Lakartidningen. - 1652-7518. ; 120:10-11
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Tidskriftsartikel (refereegranskat)abstract
- Children born before 24 gestational weeks had high neonatal morbidity and a majority had one or more neurodevelopmental disorders in addition to somatic diagnoses in childhood. Active Swedish perinatal care of infants with gestational age <24 weeks has resulted in a survival rate of more than 50 percent. Resuscitation of these immature infants is controversial, and some countries offer comfort care only. In a retrospective review of medical files and registries of 399 Swedish infants born before 24 gestational weeks, a majority had severe prematurity-related neonatal diagnoses. In childhood (2-13 years), 75 percent had at least one neurodevelopmental disorder and 88 percent had one or more prematurity-related somatic diagnosis (permanent or transient) that was likely to affect their quality of life. Long-term consequences for surviving infants should be considered in general recommendations as well as in parental information.
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| 3. |
- Hellström, Ann, 1959, et al.
(författare)
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Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity A Randomized Clinical Trial
- 2021
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Ingår i: JAMA Pediatrics. - : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 175:4, s. 359-367
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP). OBJECTIVE To determine whether enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 27 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. INTERVENTIONS Infants received either supplementation with an enteral oil providing AA (100mg/kg/d) and DHA (50mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURES The primary outcomewas severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. RESULTS A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P =.02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P <.001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P =.03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died. CONCLUSIONS AND RELEVANCE This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.
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| 4. |
- Hellström, Ann, 1959, et al.
(författare)
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Retrospective evaluation of ophthalmological and neurological outcomes for infants born before 24 weeks gestational age in a Swedish cohort
- 2022
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To retrospectively evaluate ophthalmological and neurological outcomes in a Swedish cohort of infants born before 24 weeks gestational age (GA) and explore risk factors for visual impairment. Setting Eye and paediatric clinics in Sweden. Participants Infants screened for retinopathy of prematurity (ROP) (n=399), born before 24 weeks GA, 2007-2018. Cases were excluded if ophthalmological follow-up records could not be traced. Primary and secondary outcome measures Primary outcomes were ophthalmological, including visual acuity (VA), refractive error, strabismus, nystagmus and cerebral visual impairment (CVI). Secondary outcomes comprised neonatal and neurological morbidities. Data were retrospectively retrieved from medical records. Results The 355 assessed children had a median GA of 23 weeks and 2 days and a median birth weight of 565 g. At the last available ophthalmological examination, the median age was 4.8 years (range 0.5-13.2 years). Nystagmus was recorded in 21.1%, strabismus in 34.8%, and 51.0% wore spectacles. Seventy-three of 333 (21.9%) were visually impaired, defined as being referred to a low vision clinic and/or having a VA less than 20/60 at 3.5 years of age or older. ROP treatment was a significant risk factor for visual impairment (OR 2.244, p=0.003). Visually impaired children, compared with children without visual impairment, more often had neurological deficits such as intellectual disability 63.8% versus 33.3% (p<0.001), epilepsy 21.1% versus 7.5% (p=0.001) and autism spectrum disorders 32.8% versus 20.9% (p=0.043). Nine of the 355 children had been diagnosed with CVI. Conclusions Children born before 24 weeks GA frequently had visual impairment in association with neurological deficits. CVI was rarely diagnosed. A multidisciplinary approach for the evaluation and habilitation of these vulnerable infants is warranted. National follow-up guidelines need to be developed and implemented.
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| 5. |
- Jacobson, Lena, et al.
(författare)
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Visual impairment is common in children born before 25 gestational weeks-boys are more vulnerable than girls.
- 2009
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 98:2, s. 261-5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Children born extremely preterm have high risk of visual impairment due to retinopathy of prematurity (ROP) and cerebral lesions. Objective: The aim of this study was to investigate the frequency of ROP and visual impairment as defined by the World Health Organization (WHO), with respect to gender in two hospital-based groups of children born at the limit of viability. Patients and methods: A retrospective chart review was conducted for all children (n = 114), born before 25 gestational weeks and screened for ROP at Karolinska hospital in Stockholm and Sahlgrenska hospital in Gothenburg between 1990 and 2002. Maximal ROP stages, treatment for ROP and visual acuity (VA), with correction when needed at latest available visit, were recorded. Results: Altogether 97.4% had ROP, 74.6% developed proliferative disease (stage >/= 3) and 63.2% were treated with retinal ablation. Normal VA (>/=0.8) in at least one eye was found in 50.5% of all and in significantly more girls (61.5%) than boys (34.8%) (p = 0.006), while visual impairment (VA < 0.33) was more common in boys (32.6%) than in girls (9.2%) (p = 0.004). Conclusion: A large proportion of children, especially boys, born at the level of viability are visually impaired with low vision or blindness. Development of preventive measures is urgent.
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| 6. |
- Ley, David, et al.
(författare)
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Longitudinal infusion of insulin-like growth factor-I and IGF-binding protein-3 complex to five preterm infants: pharmacokinetics and short term safety.
- 2013
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 63:1, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- Background:In preterm infants, low levels of insulin like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP).Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and decrease prevalence of ROP.Methods:In a phase II pharmacokinetic and safety study, five infants (3 girls) with a median (range) gestational age (GA) of 26+6 (26+0 - 27+2) weeks and birth weight (BW) of 990 (900-1212) g received continuous intravenous infusion of rhIGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for median (range) 168h (47-168) in doses between 21 - 111 µg/kg/24h.Results:Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (p<0.001) than model-predicted endogenous levels. Out of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within target range, 4 (5%) above and 33 (45%) were below. Predicted dose of rhIGF-I/rhIGFBP-3 to establish circulating levels of IGF-I within the intrauterine range in a 1000g infant was 75-100 µg/kg/24h. No hypoglycemia or other adverse effects were recorded.Conclusion:Continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3. Administration during study was safe.Pediatric Research (2012); doi:10.1038/pr.2012.146.
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| 7. |
- Lund, Anna My, et al.
(författare)
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Unpasteurised maternal breast milk is positively associated with growth outcomes in extremely preterm infants
- 2020
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Ingår i: Acta Paediatrica. - Oxford, UK : Wiley. - 0803-5253 .- 1651-2227. ; 109:6
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Tidskriftsartikel (refereegranskat)abstract
- Aim Extrauterine growth restriction is common among extremely preterm infants. We explored whether intake of unpasteurised maternal milk (MM) and pasteurised donor milk (DM) was associated with longitudinal growth outcomes and neonatal morbidities in extremely preterm infants. Methods Observational study of 90 preterm infants born between 2013 and 2015 in Gothenburg, Sweden. Data were prospectively collected on nutritional and breast milk intakes during the first 28 days. Results Ninety infants (39 girls and 51 boys) with a median gestational age of 25.3 (22.7-27.9) weeks were evaluated. MM intake (mL/kg/d) correlated positively with almost all z-scores for weight, length and head circumference at 28 postnatal days and at postmenstrual age (PMA) 32 and 36 weeks. After multivariable adjustment, MM intake and weight z-score at 28 postnatal days and at PMA 32 and 36 weeks remained significantly associated. Infants consuming >= 80% MM had more favourable weight z-scores at PMA 32 and 36 weeks. Intake of DM did not correlate with any growth outcomes. Infants without retinopathy of prematurity had a significantly higher intake of MM (mL/kg/d). Conclusion Unpasteurised MM was positively associated with longitudinal growth outcomes. Motivating mothers to provide their infants with their own milk after preterm birth should be emphasised.
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| 8. |
- Lundgren, Pia, 1967, et al.
(författare)
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Visual outcome at 2.5 years of age in ω-3 and ω-6 long-chain polyunsaturated fatty acid supplemented preterm infants: a follow-up of a randomized controlled trial
- 2023
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Ingår i: Lancet Regional Health-Europe. - 2666-7762. ; 32
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Tidskriftsartikel (refereegranskat)abstract
- Background We investigated ophthalmological outcomes at 2.5 years of corrected age in children born extremely preterm (EPT) to evaluate the effects of postnatal enteral supplementation with omega-3 and omega-6 long-chain polyunsaturated fatty acids.Methods In the Mega Donna Mega clinical trial, EPT infants born at less than 28 weeks of gestation were randomized to receive an enteral supplementation of docosahexaenoic acid (DHA) and arachidonic acid (AA) from birth to 40 weeks postmenstrual age. In this exploratory follow-up at 2.5 years of corrected age, we assessed visual acuity (VA), refraction, manifest strabismus, and nystagmus. Satisfactory VA was defined as >= 20/63. Multiple imputation (MI) was used to address the issue of missing data.Findings Of 178 children in the trial, 115 (with median gestational age (GA) of 25 + 4/7 weeks and median birth weights of 790 g) were ophthalmologically assessed at a median corrected age of 2.7 years (range 2.0-3.9 years). VA assessment was missing in 42.1% (75/178), in 41.7% (35/84) of the AA/DHA supplemented infants, and in 42.6% (40/94) of the control infants. After MI and adjustments for GA, study center, plurality, and corrected age at VA exam, no significant effect of AA/DHA supplementation was detected in VA outcome (>= 20/63) (odds ratio 2.16, confidence interval 95% 0.99-4.69, p = 0.053).Interpretation In this randomized controlled trial follow-up, postnatal supplementation with enteral AA/DHA to EPT children did not significantly alter VA at 2.5 years of corrected age. Due to the high loss to follow-up rate and the limited statistical power, additional studies are needed.
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| 9. |
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| 10. |
- Aring, Eva, 1959, et al.
(författare)
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Strabismus and binocular functions in a sample of Swedish children aged 4-15 years
- 2005
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Ingår i: Strabismus. - : Taylor & Francis. - 0927-3972 .- 1744-5132. ; 13:2, s. 55-61
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate strabismus, head posture, nystagmus, stereoacuity, ocular motility, near point of convergence (NPC) and accommodative convergence to accommodation ratio (AC/A) in a sample of Swedish children. METHODS: A prospective cross-sectional study was carried out on 143 children, 4-15 years of age. RESULTS: Heterotropia was found in five children (3.5%), four with esotropia and one with exotropia. One child with esotropia had a slight overaction of both inferior oblique muscles. Heterophoria was found in 37 children (26%) at near and/or distance fixation and it was four times more common at near than at distance. In 29 children, heterophoria was found at one distance only and orthophoria at the other. Orthophoria at both near and distance fixation was noted in 101 children (70.5%). The near point of convergence was < or =6 cm in 97% of the children and 97% had stereoacuity of 60" or better. In the whole group, the median AC/A ratio calculated with the heterophoria method was 5.6/1 prism diopters/diopters (PD/D) and with the gradient method, 1.3/1 PD/D. No anomalous head postures or nystagmus were observed and all children had normal versions. CONCLUSION: In this study, 143 well-defined children were investigated with a battery of accurately described tests, commonly used in clinical practice. These results are in agreement with those of other studies examining one or few variables in larger populations and the authors therefore conclude that their results may be used for comparisons with different patient groups.
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| 11. |
- Aring, Eva, 1959, et al.
(författare)
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Strabismus, binocular functions and ocular motility in children with hydrocephalus.
- 2007
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Ingår i: Strabismus. - : Informa UK Limited. - 0927-3972 .- 1744-5132. ; 15:2, s. 79-88
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate heterotropia, heterophoria, head posture, nystagmus, stereo acuity, ocular motility and near point of convergence (NPC) in children with hydrocephalus treated surgically before 1 year of age. In addition, the effects of being born with hydrocephalus, the effect of the etiology of hydrocephalus, number of shunt revisions and the size of the ventricles on these variables were studied. METHODS: A population-based study was performed in 75 children and the results were compared with the results of an age- and sex-matched group (comp group) (n = 140). RESULTS: Heterotropia 68.9% (comp group 3.6%; p < 0.001), abnormal head posture 41.3% (comp group 0; p < 0.001), nystagmus 44.0% (comp group 0; p < 0.001), stereo acuity < or =60'' 33.8% (comp group 97.1%; p < 0.001) and ocular motility defects 69.7% (comp group 0.7%; p < 0.001) were more common among children with hydrocephalus than in the comparison group. Children with overt hydrocephalus at birth had significantly more heterotropia (p = 0.0006), esotropia (p = 0.002), abnormal head posture (p = 0.02) and motility defects (p = 0.003) compared to those with hydrocephalus developing during the first year of life. The etiology, number of shunt revisions and the size of the ventricles had no significant effect on any of the investigated variables. CONCLUSIONS: Children with hydrocephalus surgically treated before the age of one year commonly present orthoptic abnormalities. The etiology of hydrocephalus, number of shunt revisions and ventricle size seem to be of minor importance compared with the age of onset of hydrocephalus with regard to the risk for orthoptic abnormalities.
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| 12. |
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| 13. |
- Danielsson, H., et al.
(författare)
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Blood protein profiles related to preterm birth and retinopathy of prematurity
- 2022
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 91:4, s. 937-946
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Tidskriftsartikel (refereegranskat)abstract
- Background Nearly one in ten children is born preterm. The degree of immaturity is a determinant of the infant's health. Extremely preterm infants have higher morbidity and mortality than term infants. One disease affecting extremely preterm infants is retinopathy of prematurity (ROP), a multifactorial neurovascular disease that can lead to retinal detachment and blindness. The advances in omics technology have opened up possibilities to study protein expressions thoroughly with clinical accuracy, here used to increase the understanding of protein expression in relation to immaturity and ROP. Methods Longitudinal serum protein profiles the first months after birth in 14 extremely preterm infants were integrated with perinatal and ROP data. In total, 448 unique protein targets were analyzed using Proximity Extension Assays. Results We found 20 serum proteins associated with gestational age and/or ROP functioning within mainly angiogenesis, hematopoiesis, bone regulation, immune function, and lipid metabolism. Infants with severe ROP had persistent lower levels of several identified proteins during the first postnatal months. Conclusions The study contributes to the understanding of the relationship between longitudinal serum protein levels and immaturity and abnormal retinal neurovascular development. This is essential for understanding pathophysiological mechanisms and to optimize diagnosis, treatment and prevention for ROP. Impact Longitudinal protein profiles of 14 extremely preterm infants were analyzed using a novel multiplex protein analysis platform combined with perinatal data. Proteins associated with gestational age at birth and the neurovascular disease ROP were identified. Among infants with ROP, longitudinal levels of the identified proteins remained largely unchanged during the first postnatal months. The main functions of the proteins identified were angiogenesis, hematopoiesis, immune function, bone regulation, lipid metabolism, and central nervous system development. The study contributes to the understanding of longitudinal serum protein patterns related to gestational age and their association with abnormal retinal neuro-vascular development.
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| 14. |
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| 15. |
- Hellgren, Gunnel, 1961, et al.
(författare)
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Serum concentrations of vascular endothelial growth factor in relation to retinopathy of prematurity.
- 2016
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Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 79, s. 70-75
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Tidskriftsartikel (refereegranskat)abstract
- The role of vascular endothelial growth factor (VEGF) in the pathogenesis of retinopathy of prematurity (ROP) has been clearly established. However, little is known about temporal changes in circulating VEGF concentrations in the preterm infant. The objective was to determine the longitudinal serum concentrations of VEGF in relation to ROP.
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| 16. |
- Hellström, Ann, 1959, et al.
(författare)
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20 000 barn blir blinda eller svårt synskadade varje år av prematuritets-retinopati
- 2016
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Ingår i: Läkartidningen. - 0023-7205. ; 113:38
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Tidskriftsartikel (refereegranskat)abstract
- Retinopathy of prematurity is a neurovascular disorder which yearly makes 20 000 infants blind or severely visually impaired worldwide. Hyperoxia is a crucial risk factor in settings with uncontrolled oxygen supplementation, while insufficient nutrient assimilation is a general contributing factor. ROP is a two phase disease with general as well as retinal neurovascular growth arrest after birth and later uncontrolled retinal neovascularization. Laser therapy prevents retinal detachment in most cases. Screening programs need to have inclusion criteria suited for the actual level of neonatal care. With less advanced care, more mature infants are affected by ROP. Risk of severe ROP can be calculated based on neonatal weight gain, especially in high quality care settings. Control of oxygen supplementation can save the sight of many infants in developing countries. Research should focus on prevention of ROP promoting postnatal growth and development. Current off-label use of anti-VEGF treatment is worrying since evidence for e.g. safety is lacking. © 2016, Swedish Medical Association. All rights reserved.
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| 17. |
- Hellström, Ann, 1959, et al.
(författare)
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Association of Docosahexaenoic Acid and Arachidonic Acid Serum Levels With Retinopathy of Prematurity in Preterm Infants
- 2021
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Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. OBJECTIVE To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28 weeks between December 20, 2016, and August 6, 2019. MAIN OUTCOMES AND MEASURES Severity of ROP was classified as no ROP, mild or moderate ROP (stage 1-2), or severe ROP (stage 3 and type 1). Serum phospholipid fatty acids were measured through gas chromatography-mass spectrometry. Ordinal logistic regression, with a description of unadjusted odds ratio (OR) as well as gestational age- and birth weight-adjusted ORs and 95% CIs, was used. Areas under the curve were used to calculate mean daily levels of fatty acids during postnatal days 1 to 28. Blood samples were obtained at the postnatal ages of 1, 3, 7, 14, and 28 days. RESULTS A total of 175 infants were included in analysis. Of these infants, 99 were boys (56.6%); the median (IQR) gestational age was 25 weeks 5 days (24 weeks 3 days to 26 weeks 6 days), and the median (IQR) birth weight was 785 (650-945) grams. A higher DHA proportion was seen in infants with no ROP compared with those with mild or moderate ROP or severe ROP (OR per 0.5-molar percentage increase, 0.49 [95% CI, 0.36-0.68]; gestational age- and birth weight-adjusted OR, 0.66 [95% CI, 0.46-0.93]). The corresponding adjusted OR for AA levels per 1-molar percentage increase was 0.83 (95% CI, 0.66-1.05). The association between DHA levels and ROP severity appeared only in infants with sufficient AA levels, suggesting that a mean daily minimum level of 7.8 to 8.3 molar percentage of AA was necessary for a detectable association between DHA level and less severe ROP. CONCLUSIONS AND RELEVANCE This cohort study found that higher mean daily serum levels of DHA during the first 28 postnatal days were associated with less severe ROP even after adjustment for known risk factors, but only in infants with sufficiently high AA levels. Further studies are needed to identify LC-PUFA supplementation strategies that may prevent ROP and other morbidities.
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| 18. |
- Hellström, Ann, 1959, et al.
(författare)
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Early weight gain predicts retinopathy in preterm infants: new, simple, efficient approach to screening
- 2009
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Ingår i: Pediatrics. - 1098-4275. ; 123:4, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The risk for sight-threatening retinopathy of prematurity is predicted by using gestational age and/or weight at birth. All infants below a threshold undergo serial ophthalmologic examinations for identification of those who would benefit from treatment (approximately 10%). We hypothesized that factoring in postnatal weight gain could identify children at risk for sight-threatening retinopathy of prematurity more specifically and earlier. METHODS: Weekly weights from birth to postmenstrual week 36 were retrospectively entered into a surveillance system that gave an alarm when the rate of weight gain decreased to a certain level. For all children (N = 354) screened and/or treated for retinopathy of prematurity at Sahlgrenska University Hospital in 2004-2007, weekly weights were recorded. One child was excluded because of known nonphysiologic weight gain (hydrocephalus). RESULTS: For 127 (36%) of 353 children, no alarm was given; for 40%, alarm at low risk was given after postmenstrual week 32. None of those children developed retinopathy of prematurity requiring treatment. Of the remaining 24% of children who received alarm at high or low risk before 32 postmenstrual weeks, 41% developed proliferative retinopathy of prematurity and 29% were treated because of sight-threatening disease. The median time from alarm to treatment was 9 weeks. CONCLUSIONS: The weight, insulin-like growth factor, neonatal retinopathy of prematurity algorithm detected early 100% of infants who developed retinopathy of prematurity requiring treatment and correctly predicted the majority who did not require treatment. With this simple postnatal evaluation, costly stressful eye examinations can be markedly reduced (approximately 75% of infants). In addition, early identification of children at risk may lead to the initiation of interventions and possibly prevent sight-threatening retinopathy of prematurity.
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| 19. |
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| 20. |
- Hellström, Ann, 1959, et al.
(författare)
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Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development.
- 2016
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 105:6, s. 576-86
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Tidskriftsartikel (refereegranskat)abstract
- Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin-like growth factor 1 (IGF-1) axis is the major hormonal mediator of growth in utero, and levels of IGF-1 are often very low after preterm birth. We reviewed the role of IGF-1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF-1 deficiency in preterm morbidities.
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| 21. |
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| 22. |
- Hellström, Ann, 1959, et al.
(författare)
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Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants
- 2016
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Ingår i: American Journal of Perinatology. - : Georg Thieme Verlag KG. - 0735-1631 .- 1098-8785. ; 33:11, s. 1067-1071
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Tidskriftsartikel (refereegranskat)abstract
- The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and, development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities.
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| 23. |
- Hellström, Ann, 1959, et al.
(författare)
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Screening and novel therapies for retinopathy of prematurity – A review
- 2019
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Ingår i: Early Human Development. - : Elsevier BV. - 0378-3782 .- 1872-6232. ; 138
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Elsevier B.V. With current screening for sight threatening retinopathy of prematurity (ROP) <10% of screened infants need treatment. Prediction models based on birth characteristics, postnatal weight gain and other factors have been developed to reduce examinations in low-risk infants. A model based on advanced statistics using data from >7000 infants registered in the Swedish ROP registry is being developed. Based on birth characteristics only, it appears to predict total risk of ROP-treatment as well as models including weight measurements. Treatment risk peaked at 12 weeks of age. Laser therapy is the method of choice for severe ROP. Anti-VEGF therapies are implemented worldwide despite insufficient knowledge of choice of drug, dosage and long term systemic effects. Prevention of ROP may be achieved through oxygen control and provision of the mother's breastmilk. Other interventions such as supplementation with long chain polyunsaturated fatty acids and preservation of fetal haemoglobin are investigated.
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| 24. |
- Hellström, Ann, 1959, et al.
(författare)
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Synproblem
- 2008
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Ingår i: Neonatologi.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 25. |
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| 26. |
- Hellström, Ann, 1959, et al.
(författare)
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Weight Gain and Retinopathy of Prematurity
- 2013
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Ingår i: Pediatric Retina. Hartnett ME, Trese M, Capone A, et al. (eds.).. - Philadelphia : Lippincott Williams & Wilkins. - 9781451151404 ; , s. 533-542
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Bokkapitel (refereegranskat)
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| 27. |
- Hård, Anna-Lena, 1949, et al.
(författare)
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Nutrition, insulin-like growth factor-1 and retinopathy of prematurity
- 2013
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Ingår i: Seminars in Fetal & Neonatal Medicine. - : Elsevier BV. - 1744-165X. ; 18:3, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- Retinopathy of prematurity is a potentially blinding disease starting with impaired retinal vessel growth in the neonatal period. Weeks to months later, peripheral retinal hypoxia induces pathologic neovascularization that may lead to retinal detachment and blindness. Current treatment strategies target late stage disease and it would be advantageous if retinopathy of prematurity could be prevented. Poor general growth after very preterm birth is a universal problem associated with increased risk of retinopathy. Loss of the maternal-fetal interaction results not only in loss of nutrients but also of other factors provided in utero. The importance of nutrition and factors such as insulin-like growth factor-1 and omega-3 long chain fatty acids for proper retinal vascularization has been defined in animal studies. Increasing evidence of the applicability of these findings to human infants is accumulating. This review focuses on factors essential for neonatal growth and possible strategies to improve growth and prevent retinopathy.
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| 28. |
- Hård, Anna-Lena, 1949, et al.
(författare)
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On safety, pharmacokinetics and dosage of bevacizumab in ROP treatment - a review.
- 2011
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 100:12, s. 1523-1527
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Tidskriftsartikel (refereegranskat)abstract
- Off label intravitreal use of the VEGF antibody bevacizumab for retinopathy of prematurity (ROP) increases despite lack of studies on safety, pharmacokinetics and dosage in developing individuals. Systemic absorption has been considered negligible. A literature search was performed with emphasis on potential adverse systemic effects in developing individuals. Intravitreal bevacizumab enters the general circulation, suppresses plasma VEGF levels and remains in the blood for more than 8 weeks in primates. Possible adverse effects on VEGF dependent development must be considered.
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| 29. |
- Hård, Anna-Lena, 1949
(författare)
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On the identification of visual defects in children in general and prematurely born children in particular
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims: Papers I & II: To evaluate the consequences of changes in the criteria for referral to an eye clinic following general pre-school vision screening. According to the former criteria all 4 year old children in the Göteborg area, with visual acuity (VA) <0.8 in either eye, were referred. Since 1992, children with slightly reduced vision (0.65 in each eye or 0.65 in one and 0.8 in the other) are retested at the age of 5.5 years and referred if visual acuity is <0.8. Papers III-V: To investigate visual functions, including visual perception, and ocular morphology in prematurely born children; a group with greatly increased risk of ophthalmologic morbidity and cognitive defects affecting visual performance.Materials and methods:Papers I & II: (I) Children referred to an eye clinic before the alteration of the criteria (n=63) and (II) children tested in the general pre-school screening after the alteration (n=483+123). For children with VA 0.65 in each eye or 0.65 in one and 0.8 in the other at 4 years of age, visual acuity, refraction, orthoptic status, slitlamp examination and ophthalmoscopy were performed, at the age of 4 and 5 years (Paper I) and at 5 years (Paper II). Papers III-V: Evaluation of ophthalmologic status and visual perception was performed on a population-based group of children born before 29 weeks of gestation (Papers III & IV; n=51) and on a group of patients, born before the 37th gestational week (Paper V), in a paediatric eye clinic with known brain lesions or signs that might indicate a brain lesion; strabismus and/or reduced visual acuity (n=91). Ocular fundus photographs were taken and analysed, using digital image analysis, regarding optic disc and retinal vessel characteristics.Results: Papers I & II: At retesting at the age of 5.5 years a majority (>70%) of the children with slightly reduced vision at the age of 4 years had a visual acuity of 0.8 or better. Few had visual defects needing treatment and among those who were treated, the results were good. Papers III-V: Ophthalmologic abnormalities were common in children born before 29 gestational weeks. These children had a smaller optic disc area, neuroretinal rim area and more than normal tortuosity of retinal vessels. Reduced visual perception was observed in 40% of the children born before 29 weeks of gestation and in 67% of children in the patient-based group with brain lesions or signs that might indicate a brain lesion.Conclusions: Papers I & II: The alteration of the screening criteria has resulted in a reduction of unnecessarily referred children while few children in need of treatment are missed. Papers III-V: Prematurely born children are at increased risk for visual problems and ocular abnormalities. Reduced visual perception is common in preterm children even in those without a diagnosis of a brain lesion. Strabismus and subnormal visual acuity in a prematurely born child should alert the ophthalmologist to the possible existence of visual perceptual problems.
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| 30. |
- Hård, Anna-Lena, 1949, et al.
(författare)
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On the use of antiangiogenetic medications for retinopathy of prematurity.
- 2011
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 100:8, s. 1063-5
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Tidskriftsartikel (refereegranskat)abstract
- In contrast to the adult, the third-trimester foetus experiences one of the most intense periods of growth and maturation of its lifetime. Early development is characterized by the existence of critical periods when environmental factors effectively produce long-lasting changes. Proliferative retinopathy of prematurity (ROP) is a potentially blinding disease characterized by uncontrolled retinal angiogenesis. This pathologic angiogenesis is the target for two new treatment modalities for ROP, i.e. intravitreal anti-VEGF (bevacizumab) and systemic propranolol, which are being evaluated in ongoing or planned studies. VEGF is essential for normal angiogenesis in a growing infant, and the adrenergic system is important for many organ systems and, in addition, for plasticity of the visual and olfactory systems. CONCLUSION: This viewpoint raises concerns regarding the currently studied antiangiogenetic treatments for ROP and their possible general effects on the developing preterm infant.
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| 31. |
- Hård, Anna-Lena, 1949, et al.
(författare)
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Ophthalmological follow-up at 2 years of age of all children previously screened for retinopathy of prematurity: is it worthwhile?
- 2006
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Ingår i: Acta Ophthalmol Scand. - : Wiley. - 1395-3907. ; 84:5, s. 631-5
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the extent to which ophthalmological follow-up at 2 years of age of children born before 32 weeks gestation identifies obvious visual problems, strabismus and significant ametropia (target conditions). METHODS: Of 172 children born during a period of 2.5 years from January 2000, 142 underwent an ophthalmological examination at a median age of 2.33 years. This included evaluation of visual behaviour, cover testing and autorefractometry in cycloplegia. For children with the target conditions, we investigated whether the child had been followed in the eye clinic or referred before 2 years of age, or whether the abnormality was detected as a result of the follow-up examination. RESULTS: None of the target conditions were found in 117 children. None of four children with obviously abnormal visual behaviour, two of 10 children with strabismus and four of 11 with large refractive errors were detected in the follow-up examination. Thus the target conditions were detected at the follow-up examination in only six of 142 children (4.2%). CONCLUSIONS: Although ophthalmic abnormalities are common in children born prematurely, most of them are identified because high-risk children are followed regularly in eye clinics and because parents and primary health care personnel detect strabismus. Ophthalmological follow-up of all children born before 32 weeks appears not to be worthwhile and is therefore only recommended for high-risk children.
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| 32. |
- Hård, Anna-Lena, 1949, et al.
(författare)
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Predicting proliferative retinopathy in a Brazilian population of preterm infants with the screening algorithm WINROP
- 2010
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Ingår i: Archives of Ophthalmology. - : American Medical Association (AMA). - 0003-9950. ; 128:11, s. 1432-1436
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To retrospectively validate the WINROP (weight, insulinlike growth factor I, neonatal, retinopathy of prematurity [ROP]) algorithm in a Brazilian population. WINROP aims to predict ROP and is based on longitudinal weight measurements from birth until postmenstrual age 36 weeks. WINROP has predicted 100% of severe ROP in 3 neonatal intensive care unit settings in the United States and Sweden. METHODS: In children admitted to the neonatal intensive care unit at Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil, from April 2002 to October 2008, weight measurements had been recorded once a week for children screened for ROP, 366 of whom had a gestational age of 32 weeks or less. The participating children had a median gestational age of 30 weeks (range, 24-32 weeks) at birth and their median birth weight was 1215 g (range, 505-2000 g). RESULTS: For 192 of 366 children (53%), no alarm or low-risk alarm after postmenstrual age 32 weeks occurred. Of these, 190 of 192 did not develop proliferative disease. Two boys with severe sepsis who were treated for ROP received low-risk alarms at postmenstrual age 33 and 34 weeks, respectively. The remaining 174 children (47%) received high- or low-risk alarms before or at 32 weeks. Of these infants, 21 (12%) developed proliferative ROP. CONCLUSIONS: In this Brazilian population, WINROP, with limited information on specific gestational age and date of weight measurement, detected early 90.5% of infants who developed stage 3 ROP and correctly predicted the majority who did not. Adjustments to the algorithm for specific neonatal intensive care unit populations may improve the results for specific preterm populations.
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| 33. |
- Hård, Anna-Lena, 1949
(författare)
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Results of vision screening of 6-year-olds at school: a population-based study with emphasis on screening limits
- 2007
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Ingår i: Acta Ophthalmol Scand. - : Wiley. - 1395-3907. ; 85:4, s. 415-8
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate newly introduced vision screening of 6-year-olds in the preschool class with special regard to screening criteria. METHODS: Monocular visual acuity (VA) testing in 6-year-olds by school nurses as part of preventive health care was introduced in Sweden 2003. Children with VA < 0.8 (logMAR 0.1) or symptoms are referred to eye clinics where VA testing, cover testing, cycloplegic autorefraction and ophthalmoscopy are performed. The present screening limit of 0.8 (logMAR 0.1) was evaluated in relation to a limit of 0.65 (logMAR 0.2). All children in the City of Gothenburg starting preschool class in 2003 were included. RESULTS: A total of 127 schools with 3885 pupils participated. Of these, 255 pupils (6.6%) were referred and 236 underwent an ophthalmological examination. Children with a VA of 0.65 (logMAR 0.2) in the worse eye constituted 74.5% of those who had failed the screening; more than half of these were found to have VA > or = 0.8 (logMAR 0.1) in the clinic. Many were not refracted in cycloplegia and only 6.7% were found to have significant ametropia. The criteria for the prescription of glasses varied; 13.4% of these children were prescribed glasses for insignificant refractive errors. CONCLUSIONS: Six-year-olds with VA of 0.65 (logMAR 0.2) rarely have defects that require treatment and the screening criterion of 0.8 (logMAR 0.1) is probably too demanding for effective utilization of available resources. Retest before referral and refraction in cycloplegia of all children with reduced VA or visual symptoms are recommended.
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| 34. |
- Hård, Anna-Lena, 1949, et al.
(författare)
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Severe ROP in twins after blockage of the renin-angiotensin system during gestation.
- 2008
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 0803-5253 .- 1651-2227. ; 97:8, s. 1142-4
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Tidskriftsartikel (refereegranskat)abstract
- Blockage of the renin-angiotensin system (RAS) during pregnancy is known to cause serious dysfunction of many organs of the foetus and newborn. Angiotensin II is an angiogenic factor and angiotensin-converting enzyme (ACE) inhibitors prevent retinal neovascularisation and their use in preventing proliferative retinopathy of prematurity has been suggested. We report on twin girls born after 32 gestational weeks, who were exposed to blockage of the RAS during gestation, had severely reduced retinal vasculature and developed severe retinopathy of prematurity (ROP) despite receiving very little extra oxygen. CONCLUSION: It is likely that ACE inhibitors and angiotensin receptor blockers not only reduce pathological neovascularisation but also normal vascularisation of the eyes and other organs.
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| 35. |
- Hård, Anna-Lena, 1949, et al.
(författare)
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Subnormal visual perception in school-aged ex-preterm patients in a paediatric eye clinic
- 2004
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Ingår i: Eye. - : Springer Science and Business Media LLC. - 0950-222X .- 1476-5454. ; 18:6, s. 628-34
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to assess visual perception at school age of children born preterm with known lesions to the posterior visual pathways or with ophthalmologic signs that might indicate such lesions. METHODS: The study group consisted of 91 patients born before the 37th gestational week. Visual perception was assessed using the TVPS-R (Test of Visual Perceptual Skills - Revised) and a structured interview. In addition, ophthalmologic and orthoptic examinations were performed. RESULTS: On the test of visual perception, 67% of the patients had results below the third percentile of the American reference group. This is to be compared with 10% of Swedish full-term controls. Scores below the third percentile were observed in 87% of the patients with known brain lesions, 48% of those with strabismus without known brain lesion, and 86% of those with reduced visual acuity in the absence of strabismus and known brain lesion. CONCLUSIONS: Reduced visual perception is common among children born preterm who have strabismus and/or reduced visual acuity, as well as in those with known brain lesions. This study emphasises the need to find tools to identify and assess those patients who have visual perceptual problems that may restrict their ability to meet the demands of daily life.
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| 36. |
- Hök Wikstrand, Margareta, 1946, et al.
(författare)
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Birth weight deviation and early postnatal growth are related to optic nerve morphology at school age in children born preterm.
- 2010
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Ingår i: Pediatric research. - 1530-0447. ; 67:3, s. 325-9
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the influence of early and later postnatal growth variables on optic disc morphology in children (n = 53) born at gestational age <32 wk. On fundus photographs taken at a median age of 5.4 y, the optic discs were evaluated using digital image analysis and compared with those of a control group (n = 203). The results were analyzed in relation to gestational age, birth weight (BW) SD score (SDS), IGF-1 weight at postmenstrual age 32 wk (SDS), and weight, length, and head circumference (SDS) at follow-up. The preterm children's optic disc and neuronal rim areas were smaller than in the control group. Low BW (SDS) and weight at wk 32 (SDS) were associated with larger area of the optic cup and reduced neuronal rim area. Preterm children with known brain lesions (n = 6) had significantly larger cups than preterm children without known brain lesions. The association found between both low BW and poor early growth and later reduced neuronal tissue of the optic nerve indicate that early weight gain is important for neural development in preterm children.
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| 37. |
- Hök Wikstrand, Margareta, 1946, et al.
(författare)
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Early postnatal growth variables are related to morphologic and functional ophthalmologic outcome in children born preterm.
- 2010
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Ingår i: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 99:5, s. 658-664
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To evaluate the association between gestational age (GA), early and late postnatal growth variables and ophthalmologic outcome in ex-preterm children. Methods: Children (GA < 32 weeks, n = 66), previously examined regarding insulin-like growth factor 1 (IGF-1) serum concentrations in relation to ROP, underwent ophthalmologic examination at median 5.6 years. Weight, height, and head circumference (HC) were measured and expressed as SDS. Growth variables were analysed in relation to ophthalmologic outcome. Results: At follow-up 74% had some ophthalmologic abnormality and 17% had visual impairment. Poor visual acuity was correlated with low GA (r(s) = 0.29, p = 0.019), low weight at 32 weeks (r(s) = 0.30, p = 0.013), and low weight (r(s) = 0.37, p = 0.0025), height (r(s) = 0.41, p = 0.0007) and HC (r(s) = 0.55, p < 0.0001) at follow-up. Hyperopic children (25%) had low neonatal IGF-1 (p = 0.0096) and HC at follow-up (p = 0.022). Poor visual perception was correlated with low early weight (r(s) = 0.38, p = 0.0036) and HC at follow-up (r(s) = 0.39, p = 0.0024). Head circumference at follow-up was correlated with GA (r(s) = 0.40, p = 0.0012), neonatal IGF-1 (r(s) = 0.37, p = 0.0031), and early weight (r(s) = 0.27, p = 0.035). Conclusions: In very preterm children, early and later postnatal growth is closely related to visual acuity and perception at follow-up. In addition, IGF-1 concentrations and early growth are correlated with head circumference and refraction at follow-up.
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| 38. |
- Hök Wikstrand, Margareta, 1946, et al.
(författare)
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Maternal and neonatal factors associated with poor early weight gain and later retinopathy of prematurity.
- 2011
-
Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253.
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To identify factors associated with poor early weight gain as reflected in an alarm system, WINROP and risk of later proliferative ROP in infants with gestational age <28 weeks. Methods: Infants with a WINROP alarm and proliferative ROP, the "alarm group" (n=23) were matched to gestational age and gender to a "no alarm group" (n=23) with no WINROP alarm and no or mild ROP. Retrospectively maternal variables, birth characteristics and neonatal factors, during the first three postnatal weeks, were compared. Results: The "alarm group" had lower birth weight and birth weight standard deviation score, longer stay in ventilator, more insulin and corticosteroid treatments, and lower white blood cell count. In a logistic regression model birth weight standard deviation score, insulin, low white blood cell count, absence of both elevated C- reactive protein and premature rupture of membranes were associated with proliferative ROP and WINROP alarm (p=0.000, r(2) = 0.704). Conclusions: This study shows that prenatal factors resulting in low birth weight have persisting effects on early postnatal growth, metabolism and inflammatory response. Future prospective studies will focus on the link between these factors and pathological retinal vessel development in the early postnatal period to find possible preventive strategies.
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| 39. |
- Lundgren, Pia, 1967, et al.
(författare)
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Aggressive Posterior Retinopathy of Prematurity Is Associated with Multiple Infectious Episodes and Thrombocytopenia
- 2017
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 111:1, s. 79-85
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 S. Karger AG, BaselBackground: The most severe form of rapidly progressing retinopathy of prematurity (ROP) is termed aggressive posterior ROP (APROP). APROP frequently causes severe visual impairment in affected preterm infants despite timely and appropriate laser treatment. Objectives: We investigated the postnatal characteristics associated with APROP development in a national Swedish cohort. Methods: This retrospective, 1:1 matched case-control study included all infants that developed APROP in zone 1 (n = 9) between 2008 and 2012. Control infants, matched for gestational age and birth weight, developed ROP no worse than stage 2 (n = 9). We retrieved data from medical records on infant birth characteristics, postnatal morbidities, and blood analyses from birth to the first ROP treatment. Infectious episodes included sepsis, C-reactive protein ≥10 mg/l, and other clinical signs of infection that required antibiotic treatment. A platelet count <100 × 109/l was considered to be thrombocytopenia. Results: All APROP cases postnatally developed at least two infectious episodes, one in the first month and one around the time of ROP diagnosis. All APROP cases exhibited thrombocytopenia in the first month, and 6/9 exhibited thrombocytopenia around the time of ROP diagnosis. Compared to the controls, APROP cases more frequently developed necrotizing enterocolitis (8/9 vs. 1/9; p < 0.01) and sepsis (9/9 vs. 3/9; p < 0.01), and they had significantly lower median platelet counts (90 × 109/l, range 4-459, vs. 158 × 109/l, range 20-500; p < 0.001). Conclusion: Multiple infectious episodes and thrombocytopenia, particularly around the time of ROP diagnosis, were associated with APROP development.
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| 40. |
- Löfqvist, Chatarina, 1964, et al.
(författare)
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Association of Retinopathy of Prematurity With Low Levels of Arachidonic Acid A Secondary Analysis of a Randomized Clinical Trial
- 2018
-
Ingår i: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 136:3, s. 271-277
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Mice with oxygen-induced retinopathy fed matched diets except for omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) vs omega-6 LC-PUFAs demonstrate relative antiangiogenic and neuroprotective associations of omega-3 LC-PUFAs. However, supplementing preterm infants with LC-PUFAs has been inconsistent in reducing major preterm morbidities. However, few studies measured serum lipid levels after supplementation. OBJECTIVE To examine the associated risk of retinopathy of prematurity (ROP) from the levels of circulating omega-3 and omega-6 LC-PUFAs. DESIGN, SETTING, AND PARTICIPANTS This longitudinal clinical study was a further analysis of serum lipid levels from a randomized controlled trial cohort of 90 infants born at gestational age (GA) less than 28 weeks. From April 4, 2013, to September 22, 2015, cord blood samples, followed by venous blood samples, were obtained at birth and at 1, 7, 14, and 28 days after birth and then at postmenstrual age (PMA) 32, 36, and 40 weeks at the neonatal intensive care unit at Sahlgrenska University Hospital in Goteborg, Sweden. MAIN OUTCOMES AND MEASURES Serum phospholipid fatty acids were transmethylated and measured by gas chromatography-mass spectrometry. Mann-Whitney test, logistic regression Spearman rank correlation, and receiver operating characteristic curve analysis were used to compare differences between infants with no ROP and infants who developed ROP. RESULTS Serum levels from 78 infants (43 male [55%]; mean [SD] GA, 25.5 [1.4] weeks) with a known ROP outcome were evaluated. Lower area under the curve (AUC) of arachidonic acid (AA) (20: 4 omega-6) was seen in infants with a later diagnosis of ROP compared with infants with no ROP in the first month of life (mean, 34.05 [95% CI, 32.10-36.00] vs 37.15 [95% CI, 34.85-39.46]; P < .05). In addition, lower levels of AA at 32 weeks' PMA were seen in infants with later severe ROP compared with in those without ROP (mean, 7.06 [95% CI, 6.60-7.52] vs 8.74 [95% CI, 7.80-9.67]; P < .001). In logistic modeling, low postnatal serum levels of AA and GA at birth identified with a sensitivity greater than 90% of infants who developed ROP. CONCLUSIONS AND RELEVANCE Low postnatal levels of the omega-6 LC-PUFAs (AA) are strongly associated with ROP development. Evaluating postnatal AA fraction after birth in addition to GA may be useful for ROP prediction.
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| 41. |
- Löfqvist, Chatarina, 1964, et al.
(författare)
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Longitudinal Postnatal Weight and Insulin-like Growth Factor I Measurements in the Prediction of Retinopathy of Prematurity
- 2006
-
Ingår i: Arch Ophthalmol. - : American Medical Association (AMA). ; 124:12, s. 1711-1718
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate whether postnatal growth and development influence retinopathy of prematurity (ROP) and may be included in screening for ROP. Design We developed an algorithm to predict for individual infants the risk of later ROP development requiring treatment based on the postnatal longitudinal systemic factors of insulin-like growth factor I (IGF-I) level, IGF binding protein 3 level, and postnatal weight gain. We developed the algorithm based on 79 preterm infants considered at risk for ROP by standard criteria (gestational age, 23.6-31.7 weeks) in a longitudinal study measuring weight gain and serum IGF-I and IGF binding protein 3 levels weekly from birth until discharge from the hospital. We monitored deviations from reference models for weight and IGF-I level (preterm children who developed no or minimal ROP) to detect indications for treatable ROP by Early Treatment for Retinopathy of Prematurity study criteria. Results This monitoring method detected 6 (100%) of 6 infants in this cohort who required treatment for ROP with a warning signal at least 5 weeks before requiring treatment and at least 3 weeks before the onset of stage 3 ROP. The majority of infants (61/73 infants) requiring no treatment were also correctly identified. Conclusions Monitoring the postnatal factors of weight, IGF-I level, and IGF binding protein 3 level substantially enhances the clinician's ability to identify patients who will require treatment for ROP.
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| 42. |
- Löfqvist, Chatarina, 1964, et al.
(författare)
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Oxygen Monitoring Reduces the Risk for Retinopathy of Prematurity in a Mexican Population
- 2016
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 110:2, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- Background: Retinopathy of prematurity (ROP), a potentially blinding disease, affects preterm infants. High levels of oxygen saturation are a well-known risk factor for ROP. Objectives: To assess the frequency of ROP type 1 needing treatment after improved oxygen monitoring (2011) in a Mexican preterm population selected for WINROP analyses and to retrospectively revalidate WINROP, an online surveillance system identifying infants at risk of developing ROP type 1. Methods: Preterm infants born with birth weight (BW) < 1,750 g and/or at gestational age (GA) <= 34 weeks, screened for ROP in 2012-2014 at the Hospital Civil de Guadalajara, Mexico were included (n = 151). Eighty-five infants with GA < 32 weeks qualified for WINROP analyses. GA, BW, maximal ROP stage, ROP treatment and weekly weights were recorded. The results in the present study were compared to those of a previous WINROP study in the same hospital (2005-2010; n = 352). Results: In the present WINROP cohort, 11.8% of the infants born at GA < 32 weeks received treatment compared to 51.0% of the infants in the previous WINROP cohort. One infant (3%) born at GA >= 32 weeks received treatment during the present study period compared to 35.6% during the previous period. WINROP displayed 80.0% sensitivity in infants born at GA < 32 weeks in the present study compared to 84.7% in the previous study. Conclusions: Uncontrolled oxygen supplementation is the major risk factor for severe ROP in infants born at GA >= 32 weeks. After improved oxygen monitoring, the frequency of ROP treatment was dramatically reduced at the Hospital Civil de Guadalajara, Mexico. (C) 2016 S. Karger AG, Basel.
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| 43. |
- Löfqvist, Chatarina, 1964, et al.
(författare)
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Postnatal head growth deficit among premature infants parallels retinopathy of prematurity and insulin-like growth factor-1 deficit
- 2006
-
Ingår i: Pediatrics. ; 117:6, s. 1930-8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We hypothesized that in premature infants, retinal vascular growth retardation between birth and postmenstrual age of approximately 30 to 32 weeks that initiates retinopathy of prematurity is paralleled by brain growth retardation. METHODS: In a prospective longitudinal study, we measured postnatal head growth, retinopathy of prematurity stage, protein and energy intake, severity of illness and serum insulin-like growth factor-1 levels in 58 preterm infants (mean gestational age at birth: 27.6 weeks) from birth until postmenstrual age of approximately 40 weeks. RESULTS: Premature infant head growth decelerates dramatically after birth until postmenstrual age of approximately 30 weeks. Head growth retardation coincides with retinal vascular growth suppression. Accelerated growth follows between post menstrual ages of approximately 30 to 32 weeks and approximately 40 weeks. The degree of head growth retardation up to postmenstrual age of 31 weeks corresponds to the degree of retinopathy of prematurity and to the degree of suppression of serum levels of insulin-like growth factor-1. At postmenstrual age of 31 weeks, if a child's head circumference SD is below -2.5, then the probability of also developing at least stage 3 retinopathy of prematurity increases fivefold compared with head circumference above -2.5 SD (32% vs 6%) suggesting parallel processes in brain and retina. Serum insulin-like growth factor-1 levels correlate positively with head circumference SD score and with the degree of retinopathy of prematurity. CONCLUSIONS: The correlation between head and retinal growth is consistent with insulin growth factor-1 being one of the postnatal growth factors involved in this multifactorial process and also suggests that factors that contribute to retinopathy of prematurity during this critical period may also affect neurological dysfunction. Additional studies are required to establish this connection.
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| 44. |
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| 45. |
- Najm, Svetlana, et al.
(författare)
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Effects of a lipid emulsion containing fish oil on polyunsaturated fatty acid profiles, growth and morbidities in extremely premature infants: A randomized controlled trial
- 2017
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Ingår i: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 20, s. 17-23
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 The Authors Background & aims The purpose of the study was to compare the effects of the parenteral emulsion SMOFlipid ® , with 15% fish oil, with Clinoleic ® on retinopathy of prematurity (ROP) and other morbidities and growth, and to compare their impact on longitudinal serum levels of fatty acids. Retinopathy of prematurity, other morbidity and growth were correlated with each parenteral lipid supplement. Methods Ninety infants born at gestational age < 28 weeks were randomized to treatment with SMOFlipid ® or Clinoleic ® . Two thirds (66%) of the infants received parenteral nutrition for up to 14 days birth (median 8, range 2–14 days), and additional 25% of the infants received for up to 28 days after birth (median 21, range 15–28 days). Cord blood samples and then venous blood samples were obtained at ages 1, 7, 14, and 28 days and at postmenstrual age (PMA) 32, 36, and 40 weeks. Breastmilk was collected at postnatal day 7, and at PMA 32 and 40 weeks. Serum phospholipid and breastmilk total fatty acids were analyzed by gas chromatography–mass spectrometry. Treatment groups were compared with regard to ROP, bronchopulmonary dysplasia, necrotizing enterocolitis, patent ductus arteriosus sepsis and growth between birth and 36 weeks. Results Infants on SMOFlipid ® had higher fractions of omega-3 LCPUFA eicosapentaenoic acid (EPA) and slightly higher omega-3 LCPUFA docosahexaenoic acid (DHA) fraction and a decreased arachidonic acid (AA) to DHA ratio from one week after birth up to 32 postmenstrual weeks compared to infants on Clinoleic ® . Treatment groups did not differ in morbidities or growth. Conclusion Supplementation with SMOFlipid ® containing 15% fish oil during parenteral nutrition increased EPA substantially, DHA marginally, reduced AA and decreased AA to DHA ratio. It did not reduce morbidity or affect growth. Since extremely preterm infants accumulate a large deficit of DHA and AA, studies on more prolonged or different levels of DHA and AA supplementation are warranted.
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| 46. |
- Palmér, Lars, et al.
(författare)
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Aicardi syndrome: presentation at onset in Swedish children born in 1975-2002
- 2006
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Ingår i: Neuropediatrics. - : Georg Thieme Verlag KG. - 0174-304X .- 1439-1899. ; 37:3, s. 154-8
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Tidskriftsartikel (refereegranskat)abstract
- In a nation-wide survey of Aicardi syndrome, defined as the onset of epilepsy in the first six months of life, agenesis of the corpus callosum (partial or total) and lacunar chorioretinopathy, 18 patients, all girls, born between 1975 and 2002 were identified in Sweden. Fifteen were definite cases and three were regarded as probable, since they only fulfilled two of three inclusion criteria in addition to other cerebral malformations and/or chorioretinal changes. Calculations based on this survey and population-based studies on epilepsy in retarded children yielded a prevalence rate in the range of 2 - 15 : 100 000 girls. All but one had an ordinary birth weight, length and head circumference for gestational age. One was born preterm, one post term. The age at diagnosis varied from three days to 12 years and decreased during the period reflecting the increased awareness of the syndrome. Eleven came to medical attention because of seizures. Six had myoclonic, four generalized tonic-clonic and eight tonic, clonic or complex partial seizures. One had hypsarrhythmia, five multifocal epileptiform activity, three bilateral independent bursts, two burst-suppression pattern, six other types of spikes and one slowing of background activity. Asymmetrical EEG abnormalities indicating independent hemispheric dysfunction were detected in 13/18 (72 %). Complete absence of the corpus callosum was found in 13/18 (72 %), although not identical with the previous group, a partial defect in 3/18 (17 %), and a thinning in 2/18 (11 %). Of 15 children with definite Aicardi syndrome, 13 had binocular and two monocular lacunae. In one of the latter two, subtle monocular lacunae were found on fundus photographs, but had been missed on repeated clinical examinations. Of three children with probable Aicardi syndrome typical lacunae were reported in one and other kinds of depigmentation in the other two. Most of the children had anomalous optic discs. Neuroimaging in infancy or early childhood combined with ophthalmological examination and ocular fundus photography will facilitate an early diagnosis of Aicardi syndrome. Seizure type and EEG abnormalities may be non-specific at onset.
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| 47. |
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| 48. |
- Pivodic, Aldina, 1978, et al.
(författare)
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Validation of DIGIROP models and decision support tool for prediction of treatment for retinopathy of prematurity on a contemporary Swedish cohort
- 2023
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Ingår i: British Journal of Ophthalmology. - : BMJ. - 0007-1161 .- 1468-2079. ; 107:8, s. 1132-1138
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims Retinopathy of prematurity (ROP) is currently diagnosed through repeated eye examinations to find the low percentage of infants that fulfil treatment criteria to reduce vision loss. A prediction model for severe ROP requiring treatment that might sensitively and specifically identify infants that develop severe ROP, DIGIROP-Birth, was developed using birth characteristics. DIGIROP-Screen additionally incorporates first signs of ROP in different models over time. The aim was to validate DIGIROP-Birth, DIGIROP-Screen and their decision support tool on a contemporary Swedish cohort. Methods Data were retrieved from the Swedish national registry for ROP (2018-2019) and two Swedish regions (2020), including 1082 infants born at gestational age (GA) 24 to <31 weeks. The predictors were GA at birth, sex, standardised birth weight and age at the first sign of ROP. The outcome was ROP treatment. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) with 95% CI were described. Results For DIGIROP-Birth, the AUC was 0.93 (95% CI 0.90 to 0.95); for DIGIROP-Screen, it ranged between 0.93 and 0.97. The specificity was 49.9% (95% CI 46.7 to 53.0) and the sensitivity was 96.5% (95% CI 87.9 to 99.6) for the tool applied at birth. For DIGIROP-Screen, the cumulative specificity ranged between 50.0% and 78.7%. One infant with Beckwith-Wiedemann syndrome who fulfilled criteria for ROP treatment and had no missed/incomplete examinations was incorrectly flagged as not needing screening. Conclusions DIGIROP-Birth and DIGIROP-Screen showed high predictive ability in a contemporary Swedish cohort. At birth, 50% of the infants born at 24 to <31 weeks of gestation were predicted to have low risk of severe ROP and could potentially be released from ROP screening examinations. All routinely screened treated infants, excluding those screened for clinical indications of severe illness, were correctly flagged as needing ROP screening.
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| 49. |
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| 50. |
- Smith, L. E., et al.
(författare)
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The Biology of Retinopathy of Prematurity How Knowledge of Pathogenesis Guides Treatment
- 2013
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Ingår i: Clinics in Perinatology. - : Elsevier BV. - 0095-5108. ; 40:2, s. 201-214
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Tidskriftsartikel (refereegranskat)abstract
- Retinopathy of prematurity occurs because the retina of a preterm infant at birth is incompletely vascularized, and if the postnatal environment does not match the in utero environment that supported retinal development, the vessels and neural retina will not grow normally. Risk factors determined from many clinical studies and animal studies fall into 2 categories: prenatal factors and postnatal factors.
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