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Ola Nilsson - One of the best experts on this subject based on the ideXlab platform.
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organization of the indian hedgehog parathyroid hormone related protein system in the Postnatal Growth plate
Journal of Molecular Endocrinology, 2011Co-Authors: Michael Chau, Patricia Forcinito, Anenisia C Andrade, Anita Hegde, Sohyun Ahn, Julian C Lui, Jeffrey Baron, Ola NilssonAbstract:In embryonic Growth cartilage, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP) participate in a negative feedback loop that regulates chondrocyte differentiation. Postnatally, this region undergoes major structural and functional changes. To explore the organization of the Ihh–PTHrP system in Postnatal Growth plate, we microdissected Growth plates of 7-day-old rats into their constituent zones and assessed expression of genes participating in the h–PTHrP feedback loop. Ihh, Patched 1, Smoothened, Gli1, Gli2, Gli3, and Pthr1 were expressed in regions analogous to the expression domains in embryonic Growth cartilage. However, PTHrP was expressed in resting zone cartilage, a site that differs from the embryonic source, the periarticular cells. We then used mice in which lacZ has replaced coding sequences of Gli1 and thus serves as a marker for active hedgehog signaling. At 1, 4, 8, and 12 weeks of age, lacZ expression was detected in a pattern analogous to that of embryonic cartilage. The findings support the hypothesis that the embryonic Ihh–PTHrP feedback loop is maintained in the Postnatal Growth plate except that the source of PTHrP has shifted to a more proximal location in the resting zone.
Gil Binenbaum - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the economic impact of modified screening criteria for retinopathy of prematurity from the Postnatal Growth and rop g rop study
Journal of Perinatology, 2020Co-Authors: John A F Zupancic, Guishuang Ying, Lauren A Tomlinson, Alejandra G De Alba Campomanes, Gil BinenbaumAbstract:The Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study showed that the addition of Postnatal weight gain to birth weight and gestational age detects similar numbers of infants with ROP, but requires examination of fewer infants. To determine the incremental cost-effectiveness of screening with G-ROP compared with conventional screening. We built a microsimulation model of a 1-year US birth cohort <32 weeks gestation, using data from the G-ROP study. We obtained resource utilization estimates from the G-ROP dataset and from secondary sources, and test characteristics from the G-ROP cohort. Among 78,281 infants nationally, screening with G-ROP detected ~25 additional infants with Type 1 ROP. This was accomplished with 36,233 fewer examinations, in 14,073 fewer infants, with annual cost savings of approximately US$2,931,980 through hospital discharge. Screening with G-ROP reduced costs while increasing the detection of ROP compared with current screening guidelines.
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validation of the Postnatal Growth and retinopathy of prematurity screening criteria
JAMA Ophthalmology, 2020Co-Authors: Gil Binenbaum, Lauren A Tomlinson, Edward F Bell, Pamela Donohue, Graham E Quinn, Alejandra G De Alba Campomanes, David G Morrison, Michael X RepkaAbstract:Importance The first Postnatal Growth and Retinopathy of Prematurity Study (G-ROP-1) developed new screening criteria with 100% sensitivity for type 1 retinopathy of prematurity (ROP) and 30% reduction of infants requiring examinations in a retrospective development cohort of 7483 infants from 29 North American hospitals in 2006-2012. Infants meeting 1 or more of the following criteria undergo examinations: gestational age less than 28 weeks or birth weight less than 1051 g; weight gain less than 120 g during age 10 to 19 days, weight gain less than 180 g during age 20 to 29 days, or weight gain less than 170 g during age 30 to 39 days; or hydrocephalus. Objective To evaluate the generalizability of the G-ROP screening criteria in a new cohort of at-risk infants. Design, Setting, and Participants This prospective validation cohort study (G-ROP-2) was conducted at 41 hospitals in the United States and Canada (25 G-ROP-1 hospitals and 16 new hospitals) from September 8, 2015, to June 13, 2017, among 3981 premature infants at risk for ROP and with known ROP outcomes. Main Outcomes and Measures Sensitivity for Early Treatment for Retinopathy of Prematurity Study type 1 ROP and potential reduction in infants receiving examinations. Results Among the 3981 infants in the study (1878 girls and 2103 boys; median gestational age, 28 weeks [range, 22-35 weeks]; median birth weight, 1072 g [range, 350-4080 g]; 1966 white; 942 black; 321 Latino; 120 Asian; 22 Native Hawaian or Pacific Islander; and 25 American Indian or Alaskan Native), the G-ROP criteria correctly predicted 219 of 219 cases of type 1 ROP (sensitivity, 100%; 95% CI, 98.3%-100%), while reducing the number of infants undergoing examinations by 35.6% (n = 1418). In a combined G-ROP-1 and G-ROP-2 cohort of 11 463 infants, the G-ROP criteria predicted 677 of 677 cases of type 1 ROP (sensitivity, 100%; 95% CI, 99.4%-100%), reducing the number of infants receiving examinations by 32.5% (n = 3730), while current criteria (birth weight Conclusions and Relevance This study found that the G-ROP screening criteria were generalizable on validation and, if used clinically in the United States and Canada, could reduce the number of infants receiving examinations. The large G-ROP cohorts provide evidence-based screening criteria that have higher sensitivity and higher specificity (fewer infants receiving examinations) for type 1 ROP than currently recommended guidelines.
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development of modified screening criteria for retinopathy of prematurity primary results from the Postnatal Growth and retinopathy of prematurity study
JAMA Ophthalmology, 2018Co-Authors: Gil Binenbaum, Lauren A Tomlinson, Edward F Bell, Pamela Donohue, Graham E Quinn, James Shaffer, Guishuang YingAbstract:Importance Current retinopathy of prematurity (ROP) guidelines, which are based on studies of high-risk infants and expert opinion, have low specificity for disease requiring treatment. Postnatal weight gain–based models improve specificity but have been limited by complexity and small development cohorts, which results in model overfitting and resultant decreased sensitivity in validation studies. Objective To develop a birth weight (BW), gestational age (GA), and weight gain (WG) prediction model using data from a broad-risk cohort of premature infants. Design, Setting, and Participants The Postnatal Growth and ROP Study was a retrospective multicenter cohort study conducted in 29 hospitals in the United States and Canada from 2006 to 2012 that included 7483 premature infants at risk for ROP with a known ROP outcome. A hybrid modeling approach was used that combined BW/GA criteria, weight comparison with expected Growth from infants without ROP, multiple Growth-interval assessments, consideration of nonphysiological WG, and user-friendly screening criteria. Numerous BW/GA levels, Postnatal age periods, time intervals, and WG percentile thresholds were evaluated to identify the most robust parameters. Main Outcome and Measures Sensitivity for Early Treatment of ROP Study type 1 ROP and potential reduction in infants who require examinations. Results Of 7483 infants, the median (SD) BW was 1099 (359) g, the median GA was 28 weeks (range, 22-35), 3575 (47.8%) were female, 3615 (48.4%) were white, 2310 (30.9%) were black, 233 (3.1%) were Asian, 93 (1.2%) were Pacific Islander, and 40 (0.5%) were American Indian/Alaskan Native. Infants who met any of 6 criteria would undergo examinations: (1) a GA of younger than 28 weeks; (2) a BW of less than 1051 g; a WG of less than 120 g, 180 g, or 170 g during ages 10 to 19, 20 to 29, or 30 to 39 days, respectively; or hydrocephalus. These criteria predicted 459 of 459 (100%) type 1 (sensitivity, 100%; 95% CI, 99.2%-100%), 524 of 524 (100%) treated, and 466 of 472 (98.7%) type 2 cases while reducing the number of infants who required examinations by 2269 (30.3%). Conclusions and Relevance This cohort study, broadly representative of infants who are undergoing ROP examinations, provides evidence-based screening criteria. With validation, the Postnatal Growth and ROP Study criteria could be incorporated into ROP screening guidelines to reduce the number of infants who require examinations in North America.
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Postnatal Growth and retinopathy of prematurity study rationale design and subject characteristics
Ophthalmic Epidemiology, 2017Co-Authors: Gil Binenbaum, Lauren A TomlinsonAbstract:ABSTRACTPurpose: Postnatal-Growth-based predictive models demonstrate strong potential for improving the low specificity of retinopathy of prematurity (ROP) screening. Prior studies are limited by inadequate sample size. We sought to study a sufficiently large cohort of at-risk infants to enable development of a model with highly precise estimates of sensitivity for severe ROP.Methods: The Postnatal Growth and ROP (G-ROP) Study was a multicenter retrospective cohort study of infants at 30 North American hospitals during 2006–2012. A total of 65 G-ROP-certified abstractors submitted data to a secure, web-based database. Data included ROP examination findings, treatments, complications, daily weight measurements, daily oxygen supplementation, maternal/infant demographics, medical comorbidities, surgical events, and weekly nutrition. Data quality was monitored with system validation rules, data audits, and discrepancy algorithms.Results: Of 11,261 screened infants, 8334 were enrolled, and 2927 had insufficie...
Jeremie Botton - One of the best experts on this subject based on the ideXlab platform.
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phthalate pregnancy exposure and male offspring Growth from the intra uterine period to five years of age
Environmental Research, 2016Co-Authors: Jeremie Botton, Claire Philippat, Antonia M Calafat, Sophie Carles, Mariealine Charles, Remy SlamaAbstract:Abstract Objective To study associations between prenatal exposure to phthalates and fetal and Postnatal Growth up to age 5 years in male offspring. Methods Eleven phthalate metabolites were quantified in spot maternal urine samples collected during gestation among 520 women of the EDEN mother-child cohort who gave birth to a boy. Fetal Growth was assessed from repeated ultrasound measurements and measurements at birth. We used repeated measures of weight and height in the first 5 years of life to model individual Postnatal Growth trajectories. We estimated adjusted variations in pre and Postnatal Growth parameters associated with an interquartile range increase in ln-transformed phthalate metabolite concentrations. Results Monocarboxyisononyl phthalate (MCNP) was positively associated with femoral length during gestation and length at birth. High molecular weight phthalate metabolites were negatively associated with estimated fetal weight throughout pregnancy. Monoethyl phthalate (MEP) showed positive association with weight Growth velocity from two to five years and with body mass index at five years (β=0.17 kg/m2, 95% confidence interval, 0.04, 0.30). Conclusions We highlighted associations between gestational exposure to some phthalates and Growth in boys. The positive association between MEP and Postnatal Growth in boys was also reported in several previous human studies.
J P Fryns - One of the best experts on this subject based on the ideXlab platform.
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severe pre and Postnatal Growth retardation developmental delay with hypotonia and marked hypotrophy of the distal extremities dental anomalies and eczematous skin a new autosomal recessive entity
Clinical Genetics, 2008Co-Authors: C Grubben, P Cecil, M Borghgrae, Herman Van Den Berghe, J P FrynsAbstract:Grubben C, De Cock P, Borghgraef M, Van den Berghe H, Fryns JP. Severe pre- and Postnatal Growth retardation, developmental delay with hypotonia and marked hypertrophy of the distal extremities, dental anomalies and eczematous skin. A new autosomal recessive entity. Clin Genet 1992:41: 16–21. We report on three young children, two girls and one boy, with pre- and Postnatal Growth deficiency, hypotonia, psychomotor retardation with notably impaired speech development, hypotrophy of the distal extremities, small hands and feet, small and widely spaced teeth, eczematous skin, and, in two of them, a partial agenesis of the corpus callosum. To our knowledge this specific combination of features has not been reported before. Since the two girls are sisters and the boy is the product of a consanguineous marriage, the inheritance of this new syndrome appears to be autosomal recessive.
Michael Chau - One of the best experts on this subject based on the ideXlab platform.
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organization of the indian hedgehog parathyroid hormone related protein system in the Postnatal Growth plate
Journal of Molecular Endocrinology, 2011Co-Authors: Michael Chau, Patricia Forcinito, Anenisia C Andrade, Anita Hegde, Sohyun Ahn, Julian C Lui, Jeffrey Baron, Ola NilssonAbstract:In embryonic Growth cartilage, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP) participate in a negative feedback loop that regulates chondrocyte differentiation. Postnatally, this region undergoes major structural and functional changes. To explore the organization of the Ihh–PTHrP system in Postnatal Growth plate, we microdissected Growth plates of 7-day-old rats into their constituent zones and assessed expression of genes participating in the h–PTHrP feedback loop. Ihh, Patched 1, Smoothened, Gli1, Gli2, Gli3, and Pthr1 were expressed in regions analogous to the expression domains in embryonic Growth cartilage. However, PTHrP was expressed in resting zone cartilage, a site that differs from the embryonic source, the periarticular cells. We then used mice in which lacZ has replaced coding sequences of Gli1 and thus serves as a marker for active hedgehog signaling. At 1, 4, 8, and 12 weeks of age, lacZ expression was detected in a pattern analogous to that of embryonic cartilage. The findings support the hypothesis that the embryonic Ihh–PTHrP feedback loop is maintained in the Postnatal Growth plate except that the source of PTHrP has shifted to a more proximal location in the resting zone.
