| 1. |
- Pivodic, Aldina, 1978, et al.
(författare)
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Individual Risk Prediction for Sight-Threatening Retinopathy of Prematurity Using Birth Characteristics
- 2020
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Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 138:1, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- Importance: To prevent blindness, repeated infant eye examinations are performed to detect severe retinopathy of prematurity (ROP), yet only a small fraction of those screened need treatment. Early individual risk stratification would improve screening timing and efficiency and potentially reduce the risk of blindness. Objectives: To create and validate an easy-to-use prediction model using only birth characteristics and to describe a continuous hazard function for ROP treatment. Design, Setting, and Participants: In this retrospective cohort study, Swedish National Patient Registry data from infants screened for ROP (born between January 1, 2007, and August 7, 2018) were analyzed with Poisson regression for time-varying data (postnatal age, gestational age [GA], sex, birth weight, and important interactions) to develop an individualized predictive model for ROP treatment (called DIGIROP-Birth [Digital ROP]). The model was validated internally and externally (in US and European cohorts) and compared with 4 published prediction models. Main Outcomes and Measures: The study outcome was ROP treatment. The measures were estimated momentary and cumulative risks, hazard ratios with 95% CIs, area under the receiver operating characteristic curve (hereinafter referred to as AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Among 7609 infants (54.6% boys; mean [SD] GA, 28.1 [2.1] weeks; mean [SD] birth weight, 1119 [353] g), 442 (5.8%) were treated for ROP, including 142 (40.1%) treated of 354 born at less than 24 gestational weeks. Irrespective of GA, the risk for receiving ROP treatment increased during postnatal weeks 8 through 12 and decreased thereafter. Validations of DIGIROP-Birth for 24 to 30 weeks' GA showed high predictive ability for the model overall (AUC, 0.90 [95% CI, 0.89-0.92] for internal validation, 0.94 [95% CI, 0.90-0.98] for temporal validation, 0.87 [95% CI, 0.84-0.89] for US external validation, and 0.90 [95% CI, 0.85-0.95] for European external validation) by calendar periods and by race/ethnicity. The sensitivity, specificity, PPV, and NPV were numerically at least as high as those obtained from CHOP-ROP (Children's Hospital of Philadelphia-ROP), OMA-ROP (Omaha-ROP), WINROP (weight, insulinlike growth factor 1, neonatal, ROP), and CO-ROP (Colorado-ROP), models requiring more complex postnatal data. Conclusions and Relevance: This study validated an individualized prediction model for infants born at 24 to 30 weeks' GA, enabling early risk prediction of ROP treatment based on birth characteristics data. Postnatal age rather than postmenstrual age was a better predictive variable for the temporal risk of ROP treatment. The model is an accessible online application that appears to be generalizable and to have at least as good test statistics as other models requiring longitudinal neonatal data not always readily available to ophthalmologists.
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| 2. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:11, s. 4342-4350
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH).OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls.DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden.INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated.SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population.MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS.RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations.CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.
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| 3. |
- Andersson, Björn, 1939, et al.
(författare)
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Seasonal variations in vitamin D in relation to growth in short prepubertal children before and during first year growth hormone treatment
- 2015
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Ingår i: Journal of Endocrinological Investigation. - : Springer Science and Business Media LLC. - 0391-4097 .- 1720-8386. ; 38:12, s. 1309-1317
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Tidskriftsartikel (refereegranskat)abstract
- Purpose This study investigated the relationship between seasonal variations in 25-hydroxyvitamin D (25(OH) D) levels and growth in prepubertal children during both the pretreatment year and the first year of GH treatment. Methods The study included 249 short prepubertal children with a broad range of GH secretion, GH(max) during a 24 h profile median 23; range 1-127 mU/L, 191 boys (mean age +/- SD, 8.6 +/- 2.6 years), 58 girls (7.5 +/- 1.9 years) receiving GH treatment (mean 43 mu g/kg/day; range 17-99 mu g/kg/day). Serum 25(OH) D was measured using an automated IDS-iSYS immunoassay. Results 25(OH) D levels showed seasonal variation, and decreased significantly during GH treatment. 25(OH) D levels at start and first year reduction in 25(OH) D, correlated (-) with the first year growth response during treatment. The degree of GH secretion capacity within our study population of mainly non-GH deficient children and 25(OH) D sufficient (67 +/- 29 nmol/L) had no influence on 25(OH) D levels. Growth during GH treatment were independent of seasonal variations in 25(OH) D. Multiple regression analysis showed that 25(OH) D levels at treatment start, together with auxological data and IGF-binding protein-3(SDS), explained 61 % of the variation in first year gain in height(SDS). Conclusion 25(OH) D levels were associated with first year growth response to GH and may be a useful contribution to future growth prediction models.
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| 4. |
- Pivodic, Aldina, 1978, et al.
(författare)
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Development and validation of a new clinical decision support tool to optimize screening for retinopathy of prematurity
- 2022
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Ingår i: British Journal of Ophthalmology. - : BMJ Publishing Group Ltd. - 0007-1161 .- 1468-2079. ; 106:11, s. 1573-1580
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Prematurely born infants undergo costly, stressful eye examinations to uncover the small fraction with retinopathy of prematurity (ROP) that needs treatment to prevent blindness. The aim was to develop a prediction tool (DIGIROP-Screen) with 100% sensitivity and high specificity to safely reduce screening of those infants not needing treatment. DIGIROP-Screen was compared with four other ROP models based on longitudinal weights.METHODS: Data, including infants born at 24-30 weeks of gestational age (GA), for DIGIROP-Screen development (DevGroup, N=6991) originate from the Swedish National Registry for ROP. Three international cohorts comprised the external validation groups (ValGroups, N=1241). Multivariable logistic regressions, over postnatal ages (PNAs) 6-14 weeks, were validated. Predictors were birth characteristics, status and age at first diagnosed ROP and essential interactions.RESULTS: ROP treatment was required in 287 (4.1%)/6991 infants in DevGroup and 49 (3.9%)/1241 in ValGroups. To allow 100% sensitivity in DevGroup, specificity at birth was 53.1% and cumulatively 60.5% at PNA 8 weeks. Applying the same cut-offs in ValGroups, specificities were similar (46.3% and 53.5%). One infant with severe malformations in ValGroups was incorrectly classified as not needing screening. For all other infants, at PNA 6-14 weeks, sensitivity was 100%. In other published models, sensitivity ranged from 88.5% to 100% and specificity ranged from 9.6% to 45.2%.CONCLUSIONS: DIGIROP-Screen, a clinical decision support tool using readily available birth and ROP screening data for infants born GA 24-30 weeks, in the European and North American populations tested can safely identify infants not needing ROP screening. DIGIROP-Screen had equal or higher sensitivity and specificity compared with other models. DIGIROP-Screen should be tested in any new cohort for validation and if not validated it can be modified using the same statistical approaches applied to a specific clinical setting.
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| 5. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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New Reference for Height in Swedish Boys and Girls
- 2014
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Ingår i: Hormone Research in Paediatrics. 82 (suppl 1), s. 256. 53rd Annual Meeting of the European Society for Paediatric Endocrinology (ESPE). Dublin, Ireland, September 18-20, 2014. Hormone Research in Paediatrics.. - : S. Karger AG. - 1663-2818 .- 1663-2826.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: The actual Swedish growth references are based on a cohort born 1974. Objective and hypotheses: Due to secular changes there is need for new height references. Method: Material: Height measurements from birth to adult height (AH) in a cohort of healthy, Nordic and born full term 1990, 20.796 from 1647 boys, 19.202 from 1501 girls were used (ALL) and compared to both a subgroup with puberty close to mean (PHV G0.25 years) of 3.726 heights from 259 boys; 3.759 from 271 girls, and a subgroup (AM) with O10 height measurements evenly distributed (15.324 in 989 boys; 14.381 in 919 girls), and of high data quality. The 1974 cohort, with similar subgrouping, were used for comparison. Methods: For construction of height curves the LMS method was applied with LMS parameters based directly on the data: the power in the Box-Cox transformation (L), the median (M), and the generalized coefficient of variation (S). The GAMLSS R-package with a special LMS program was used, giving L, M, S and optional kurtosis as functions of age. Results: Height reference curves, with mean, G1, G2 SDS were obtained for 1990 of the ALL vs the AM material with similar results whereas the close puberty material showed the same mean but more narrow G1, G2 SDS during adolescence. When the different 1990 references were compared to 1974 references, the corresponding 1974 differences were found. The new references takes into account that the 1990 cohort had a more rapid infancy growth, increased prepubertal growth, especially in boys, increased pubertal gain, only in girls, and increased AH in both genders.
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| 6. |
- Andersson, Björn, 1939, et al.
(författare)
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Short-term changes in bone formation markers following growth hormone (GH) treatment in short prepubertal children with a broad range of GH secretion
- 2015
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Ingår i: Clinical Endocrinology. - : Wiley: 12 months. - 0300-0664 .- 1365-2265. ; 82:1, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesGrowth hormone (GH) promotes longitudinal growth and bone modelling/remodelling. This study investigated the relationship between levels of bone formation markers and growth during GH treatment in prepubertal children with widely ranging GH secretion levels. MethodsThe study group comprised 113 short prepubertal children (mean ageSD, 937213years; 99 boys) on GH treatment (330 +/- 006g/kg/day) for 1year. Blood samples were taken at baseline and 1 and 2weeks, 1 and 3months, and 1year after treatment start. Intact amino-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BALP) and osteocalcin were measured using an automated IDS-iSYS immunoassay system. ResultsIntact amino-terminal propeptide of type I procollagen (PINP), BALP and osteocalcin, increased in the short-term during GH treatment. PINP after 1week (P=000077), and BALP and osteocalcin after 1month (Pless than00001 and P=00043, respectively). PINP levels at 1 and 3months correlated positively, and osteocalcin levels at 1week and percentage change after 1month correlated negatively, with first year growth response. No significant correlations were found between BALP and first year growth. Multiple regression analysis showed that bone marker levels together with auxological data and insulin-like growth factor binding protein-3 explained the variation in first year growth response to 36% at start, 32% after 2weeks and 48% at 3months. ConclusionShort-term increases in levels of the bone formation markers PINP, BALP and osteocalcin showed different temporal patterns, but all correlated with first year growth response during GH treatment. These markers may be a useful addition to existing prediction models for growth response.
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| 7. |
- Andersson, B., et al.
(författare)
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Vitamin D status in children over three decades - Do children get enough vitamin D?
- 2016
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Ingår i: Bone Reports. - : Elsevier BV. - 2352-1872. ; 5, s. 150-152
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D is a key player in the endocrine regulation of calcium and phosphate metabolism and plays a pivotal role in the acquisition of bone mass during childhood. This study investigated long-term data of vitamin D levels in children and adolescents between 1 and 18 years of age. Serum 25-hydroxyvitamin D (25(OH)D) was analyzed between 1982 and 2013 in 2048 Swedish Caucasian children (mean age ± SD, 8.59 ± 3.68 years; 1197 boys). Overall, 704 (34%) children had below recommended levels of 50 nmol/L; however, only 63 (3%) had levels below 25 nmol/L, i.e., vitamin D deficiency. No trend for decreased vitamin D levels over time was found in this population, with median 25(OH)D levels of 58.4 nmol/L, minimum-maximum 5.0-159.3 nmol/L. Younger children, independent of gender, had significantly higher levels 25(OH)D. © 2016.
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| 8. |
- Holmgren, Anton, et al.
(författare)
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Gender Difference in Secular Trend in Sweden
- 2014
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Ingår i: Hormone Research in Paediatrics. 82 (suppl 1), s. 132. - : S. Karger AG. - 1663-2818 .- 1663-2826.
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Konferensbidrag (refereegranskat)abstract
- Background, objective and hypotheses: By using QEPS, a new mathematic growth model, different components of growth can be analyzed, comparing secular trends of prepubertal and pubertal growth in Swedish birth cohorts born 1974 and 1990. Materials and methods: Two birth cohorts followed to adult height (AH) born around 1974 (1691 boys; 1666 girls) and 1990 (1647 boys; 1501 girls) being healthy, Nordic and born term. A subpopulation of 1974 (1177 boys; 1168 girls) and 1990 (989 boys; 919 girls) with < 10 height measurements evenly distributed during growth phases, and high data quality was used for comparison. The different components of the QEPS-model: (Q)uadratic, (E)xponential, (P)ubertal, and (S)top function were estimated with corresponding maximum values at AH and tempo adjusting ‘time scale ratios’ of E and P. Multivariate regression analyses were used for explaining the variation of AH. Results: Both boys and girls born 1990 compared to those born 1974 had at birth an increased lengthSDS and weightSDS and during infancy a more rapid growth (shorter Etimescale). Boys -1990 had increased prepubertal growth (P= 0.0001 for Qmax, Qheightscale), their pubertal part of growth was not significantly changed. Their AHcm increased 1.3 from 180.4 to 181.7; the variation in AH was explained to 44% by mid parental height (MPH) and birth characteristics, to 72% by adding Qmax, to 75% by pubertal onset age and to 99% by Pmax. Girls -1990 had prepubertal growth increased (P=0.05 for Qmax, Qheightscale). Their pubertal gain was markedly increased (P=0.001 for Pmax; Pheightscale), and duration decreased whereas mean menarche age remained 12.8 years. AHcm increased 0.7 from 167.6 to 168.3. AH could be explained to 52% by MPH and birth characteristics, to 71% by adding Qmax, to 75% by pubertal onset, and to 99% by Pmax. Conclusion: In cohorts born 16-years apart; a secular trend with increased AHcm was found, 1.3 in boys, due to more prepubertal growth, 0.7 in girls, due to more pubertal growth, indicating gender specific underlying regulations.
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| 9. |
- Holmgren, Anton, et al.
(författare)
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The Pubertal Gain in Height is Inversely Related to BMI in Childhood
- 2015
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Ingår i: Hormone Research in Paediatrics. ; 84:Supplement 1, s. 268-69
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Weight in childhood may influence the pubertal timing and pattern of growth. Objective: To investigate the impact of BMI in childhood on further growth, especially the specific pubertal pattern of growth. Method: The longitudinally followed GrowUpGothenburg1990 birth cohort, was analyzed using the QEPS growth model (Nierop et al. Horm Res in Ped.2013; 80(suppl 1):152–153) (describing total height as a combination of four mathematical functions; Quadratic – Q, Exponential – E, Pubertal – P and Stop – S). Individual BMISDS values, from 3.5–8 years of age were calculated for linear and subgroup analyses (low/normal – Lw/Nw, overweight/obese – Ow/Ob), based on the IOTF 2012 reference (Cole TJ, Lobstein T. Pediatric obesity. 2012; 7(4):284–94.). Results: Across the whole BMI range a negative dose-response effect of childhood BMI on pubertal gain (Pmax) was found. Already at birth Owob children were heavier, and they grew faster in height in the prepubertal period compared to Lw/Nw, as evidenced by an increased Q function. Owob children of both genders had earlier puberty (91–117 days), P = 0.0004, reduced growth during puberty, boys/girls 3.13/2.26 cm less pubertal gain P<0.0001, from the specific pubertal growth function (Pmax). The adult height was not related to BMI in childhood. Conclusion: The higher BMI in childhood, the faster the prepubertal growth, the earlier onset of puberty, the less pubertal gain. This was evident across the whole BMI-range, making weight status an important modifier of growth. Funding information: This work was supported by the Swedish Research Council (VR no 7509 and VR 2006-7777), VR/FORMAS/FORTE/VINNOVA (259-2012-38 and 2006-1624); EpiLife-TEENS research program, Pfizer AB, the Governmental Grants for University Hospital Research (ALF), the R&D Department, County of Halland, and the Foundation Växthuset for children.
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| 10. |
- Lundberg, Elena, et al.
(författare)
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Broad variability in pharmacokinetics of GH following rhGH injections in children
- 2018
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 40, s. 61-68
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Daily subcutaneous self-injection of GH is used worldwide to treat short stature in childhood; longitudinal data on the impact of this regimen on GH-uptake are lacking. Design: Children with/without GH-deficiency participating in clinical trials were followed prospectively ( s 8 times). Blood was sampled pre-GH-injection (dose GH(33)/GH(67) mu g/kg) and either every 30 min thereafter for 24 h (Experimental-setting; 59 GH-curves/15 children); or every 2 h thereafter for 16 h (Clinical-setting; 429 GHcurves/117 children). Pharmacokinetics were estimated by time T-max (h) of maximal GH-concentration (C-max , mU/L) and area under the curve for 16 h (AUC, mU/L * h). Results: In the Clinical-setting, median C-max was 71 mU/L and AUC was 534 mU/L * h, with coefficients of variation for intra-individual variation of 39% and 36%, respectively, and inter-individual variation of 44% and 42%, respectively. 43% of C-max and AUC variability was explained by GH-dose and proxies for injection depth (baseline GH-level, GH(peak) width, BMISDS). In the Experimental- versus Clinical-setting, 85% and 40% of GH-curves, respectively, reached zero-levels within 24 h. A longer duration was found following a more superficial GH-injection. Spontaneous GH-peaks were identified already 6 h after the GH-injection in about half of the curves of both GHD and non-GHD patients. Conclusion: Very broad intra-individual and inter-individual variability was found. A high GH-peak will optimize growth effects; the highest C-max was found after a deep injection of GH at the higher dose and concentration. In as many as 60% of the children, GH remained detectable in serum after 24 h; a constant GH-level will promote IGF-I and metabolic effects.
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