78 results on '"Shapira SK"'
Search Results
2. Primary Care Provider Management of Congenital Hypothyroidism Identified Through Newborn Screening
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Rosenthal, NA, Bezar, E, Mann, S, Bachrach, LK, Banerjee, S, Geffner, ME, Gottschalk, M, Shapira, SK, Hasegawa, L, and Feuchtbaum, L
- Subjects
Article - Abstract
To assess Primary Congenital Hypothyroidism (CH) management patterns and feasibility of providing long-term care for patients with CH identified through newborn screening by Primary Care Providers (PCPs) in California and Hawaii.A survey was mailed to all physicians (N=823) listed as the referral doctor for confirmed patients with CH identified through newborn screening programs in both states between 01/01/2009-12/31/2013. Information was collected on CH management patterns, barriers to providing care, and knowledge on CH treatment. Descriptive statistics and bivariate logistic regression results were reported.206 PCPs completed the survey. Among these, 78% currently have patients with CH and 91% indicated willingness to provide long-term care to new patients with CH. Among PCPs currently caring for patients with CH, 17% managed CH by themselves with limited assistance from endocrinologists; 63% were involved in managing CH but endocrinologists played a larger role than PCPs; 19% were not involved in CH care. Only 49% of PCPs correctly answered questions regarding recommended follow-up frequencies and 23% knew the correct age for a trial off levothyroxine for suspected transient CH. Top two perceived barriers to providing long-term care included "need guidance or support from endocrinologists" (61%) and "not familiar with CH treatment guidelines" (28%).The majority of PCPs surveyed are willing to provide long-term care to patients with CH, but need support from endocrinologists and increased knowledge about current treatment guidelines.
- Published
- 2017
3. Molecular and clinical characterization of a patient with duplication of 1p36.3 and metopic synostosis
- Author
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Heilstedt, HA, primary, Shapira, SK, additional, Gregg, AR, additional, and Shaffer, LG, additional
- Published
- 1999
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4. Birth prevalence rates of newborn screening disorders in relation to screening practices in the United States.
- Author
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Hertzberg VS, Hinton CF, Therrell BL, and Shapira SK
- Published
- 2011
5. EPH89 Telehealth Utilization Among Children with Autism Spectrum Disorder in Employer-Sponsored Plans, 2019–2022.
- Author
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Lamsal, R, Grosse, SD, and Shapira, SK
- Published
- 2024
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6. Prevalence of Developmental, Psychiatric, and Neurologic Conditions in Older Siblings of Children with and without Autism Spectrum Disorder: Study to Explore Early Development.
- Author
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Fields VL, Tian LH, Wiggins LD, Soke GN, Overwyk K, Moody E, Reyes N, Shapira SK, and Schieve LA
- Abstract
This study evaluated developmental, psychiatric, and neurologic conditions among older siblings of children with and without autism spectrum disorder (ASD) to understand the extent of familial clustering of these diagnoses. Using data from the Study to Explore Early Development, a large multi-site case-control study, the analyses included 2,963 children aged 2-5 years with ASD, other developmental disabilities (DD group), and a population-based control group (POP). Percentages of index children with older siblings with select developmental, psychiatric, and neurologic conditions were estimated and compared across index child study groups using chi-square tests and multivariable modified Poisson regression. In adjusted analyses, children in the ASD group were significantly more likely than children in the POP group to have one or more older siblings with ASD, developmental delay, attention-deficit/hyperactivity disorder, intellectual disability, sensory integration disorder (SID), speech/language delays, or a psychiatric diagnosis (adjusted prevalence ratio [aPR] range: 1.4-3.7). Children in the DD group were significantly more likely than children in the POP group to have an older sibling with most of the aforementioned conditions, except for intellectual disability and psychiatric diagnosis (aPR range: 1.4-2.2). Children in the ASD group were significantly more likely than children in the DD group to have one or more older siblings with ASD, developmental delay, SID, or a psychiatric diagnosis (aPR range: 1.4-1.9). These findings suggest that developmental disorders cluster in families. Increased monitoring and screening for ASD and other DDs may be warranted when an older sibling has a DD diagnosis or symptoms., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
- Published
- 2024
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7. Prenatal ultrasound use and risk of autism spectrum disorder: Findings from the case-control Study to Explore Early Development.
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Christensen D, Pazol K, Overwyk KJ, England LJ, Alexander AA, Croen LA, Dowling NF, Schieve LA, Tian LH, Tinker SC, Windham GC, Callaghan WM, and Shapira SK
- Subjects
- Child, Child, Preschool, Female, Humans, Pregnancy, Case-Control Studies, Mothers, Ultrasonography, Prenatal, Autism Spectrum Disorder diagnosis, Autism Spectrum Disorder epidemiology, Autism Spectrum Disorder etiology, Pregnancy Complications
- Abstract
Background: Studies evaluating the association between prenatal ultrasounds and autism spectrum disorder (ASD) have largely produced negative results. Concern remains due to the rising identification of children with ASD and ultrasound use., Objective: To evaluate the association between prenatal ultrasound use and ASD., Methods: We used data from the Study to Explore Early Development, a multisite case-control study of preschool-aged children with ASD implemented during 2007-2012. We recruited cases from children receiving developmental disability services and randomly selected population controls from birth records. ASD case status was based on in-person standardised assessments. We stratified analyses by pre-existing maternal medical conditions and pregnancy complications associated with increased ultrasound use (ultrasound indications) and used logistic regression to model case status by increasing ultrasound counts. For pregnancies with medical record data on ultrasound timing, we conducted supplementary tests to model associations by trimester of exposure., Results: Among 1524 singleton pregnancies, ultrasound indications were more common for ASD cases than controls; respectively, for each group, no indications were reported for 45.1% and 54.2% of pregnancies, while ≥2 indications were reported for 26.1% and 18.4% of pregnancies. The percentage of pregnancies with multiple ultrasounds varied by case status and the presence of ultrasound indications. However, stratified regression models showed no association between increasing ultrasound counts and case status, either for pregnancies without (aOR 1.01, 95% CI 0.92, 1.11) or with ultrasound indications (aOR 1.01, 95% CI 0.95, 1.08). Trimester-specific analyses using medical record data showed no association in any individual trimester., Conclusions: We found no evidence that prenatal ultrasound use increases ASD risk. Study strengths included gold-standard assessments for ASD case classification, comparison of cases with controls, and a stratified sample to account for conditions associated both with increased prenatal ultrasound use and ASD., (© 2023 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)
- Published
- 2023
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8. Progress in expanding newborn screening in the United States.
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Grosse SD, Cuthbert C, Gaffney M, Gaviglio A, Hinton CF, Kellar-Guenther Y, Kemper AR, McKasson S, Ojodu J, Riley C, Singh S, Sontag MK, and Shapira SK
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- Infant, Newborn, United States, Humans, Neonatal Screening
- Published
- 2023
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9. Health Supervision for Children and Adolescents With Down Syndrome.
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Bull MJ, Trotter T, Santoro SL, Christensen C, Grout RW, Burke LW, Berry SA, Geleske TA, Holm I, Hopkin RJ, Introne WJ, Lyons MJ, Monteil DC, Scheuerle A, Stoler JM, Vergano SA, Chen E, Hamid R, Downs SM, Grout RW, Cunniff C, Parisi MA, Ralston SJ, Scott JA, Shapira SK, and Spire P
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- Adolescent, Child, Health Promotion, Humans, Down Syndrome therapy
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- 2022
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10. State-specific prevalence of current e-cigarette use by disability status and disability type-United States, BRFSS 2016-2018.
- Author
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Zhang QC, Courtney-Long EA, Sinclair LB, Reese S, Armour BS, and Shapira SK
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- Adolescent, Adult, Behavioral Risk Factor Surveillance System, Cross-Sectional Studies, Humans, Population Surveillance, Prevalence, United States epidemiology, Young Adult, Disabled Persons, Electronic Nicotine Delivery Systems, Vaping epidemiology
- Abstract
Background: Cigarette smoking is the leading cause of preventable disease and death in the United States. The tobacco product landscape has diversified to include electronic cigarettes (e-cigarettes). Adults with disabilities are more likely than adults without disabilities to smoke cigarettes, but within the current body of literature, there is limited information on the use of e-cigarettes among adults with disabilities., Objective: To assess overall and state-specific prevalence of current e-cigarette use among adults by disability status, disability type, sex, and age., Methods: Disability was defined as having serious difficulty with vision, hearing, mobility, cognition, or any difficulty with self-care or independent living. The Behavioral Risk Factor Surveillance System cross-sectional survey data (2016-2018; n = 1,150,775) were used to estimate state and District of Columbia prevalence of current e-cigarette use among adults (aged ≥18 years) with and without disabilities, overall and by disability type, sex, and age group., Results: Median prevalence of current e-cigarette use was higher among adults with than without disabilities (6.5% vs. 4.3%, P < 0.05). Among adults with disabilities, use varied from 2.5% in DC to 10.0% in Colorado; median use was highest among those with cognitive disabilities (10.0%) and those aged 18-24 years (18.7%)., Conclusions: Prevalence of current e-cigarette use was higher among adults with than without disabilities and varied across states by disability status, type, and age group. The findings underscore the need to monitor e-cigarette use among adults with disabilities and specifically include them in tobacco control policies and programs addressing e-cigarette use., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2022
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11. Infants with Congenital Disorders Identified Through Newborn Screening - United States, 2015-2017.
- Author
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Sontag MK, Yusuf C, Grosse SD, Edelman S, Miller JI, McKasson S, Kellar-Guenther Y, Gaffney M, Hinton CF, Cuthbert C, Singh S, Ojodu J, and Shapira SK
- Subjects
- Congenital Abnormalities epidemiology, Humans, Infant, Newborn, Prevalence, United States epidemiology, Congenital Abnormalities diagnosis, Neonatal Screening
- Abstract
Newborn screening (NBS) identifies infants at risk for congenital disorders for which early intervention has been shown to improve outcomes (1). State public health programs are encouraged to screen for disorders on the national Recommended Uniform Screening Panel (RUSP), which increased from 29 disorders in 2005 to 35 in 2018.* The RUSP includes hearing loss (HL) and critical congenital heart defects, which can be detected through point-of-care screening, and 33 disorders detected through laboratory screening of dried blood spot (DBS) specimens. Numbers of cases for 33 disorders on the RUSP (32 DBS disorders and HL) reported by 50 U.S. state programs were tabulated. The three subtypes of sickle cell disease (SCD) listed as separate disorders on the RUSP (S,S disease; S,beta-thalassemia; and S,C disease) were combined for the current analysis, and the frequencies of the resulting disorders were calculated relative to annual births. During 2015-2017, the overall prevalence was 34.0 per 10,000 live births. Applying that frequency to 3,791,712 live births in 2018,
† approximately 12,900 infants are expected to be identified each year with one of the disorders included in the study. The most prevalent disorder is HL (16.5 per 10,000), and the most prevalent DBS disorders are primary congenital hypothyroidism (CH) (6.0 per 10,000), SCD (4.9 per 10,000), and cystic fibrosis (CF) (1.8 per 10,000). Notable changes in prevalence for each of these disorders have occurred since the previous estimates based on 2006 births (2). The number of infants identified at a national level highlights the effect that NBS programs are having on infant health through early detection, intervention, and potential improved health, regardless of geographic, racial/ethnic, or socioeconomic differences., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Sari Edelman, Cynthia F. Hinton, Yvonne Kellar-Guenther, Sarah McKasson, Joshua I. Miller, Jelili Ojodu, Marci K. Sontag, Sikha Singh, and Careema Yusuf report grants from Health Resources and Services Administration during the conduct of the study. No other potential conflicts of interest were disclosed.- Published
- 2020
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12. Treatment Discontinuation within 3 Years of Levothyroxine Initiation among Children Diagnosed with Congenital Hypothyroidism.
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Kemper AR, Grosse SD, Baker M, Pollock AJ, Hinton CF, and Shapira SK
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- Female, Follow-Up Studies, Hormone Replacement Therapy methods, Humans, Infant, Infant, Newborn, Male, Prognosis, Retrospective Studies, Time Factors, Congenital Hypothyroidism drug therapy, Guideline Adherence, Thyroxine therapeutic use, Withholding Treatment
- Abstract
Objectives: To measure the rates of thyroid gland imaging and levothyroxine (L-T
4 ) discontinuation and to assess whether discontinuation was monitored with thyroid-stimulating hormone testing in subjects with congenital hypothyroidism., Study Design: This is a retrospective analysis of claims data from the IBM MarketScan Databases for children born between 2010 and 2016 and continuously enrolled in a noncapitated employer-sponsored private health insurance plan or in Medicaid for ≥36 months from the date of the first filled L-T4 prescription., Results: There were 263 privately insured and 241 Medicaid-enrolled children who met the inclusion criteria. More privately insured than Medicaid-enrolled children had imaging between the first filled prescription and 180 days after the last filled prescription (24.3% vs 12.9%; P = .001). By 36 months, 35.7% discontinued L-T4 , with no difference by insurance status (P = .48). Among those who discontinued, 29.1% of privately insured children and 47.7% of Medicaid-enrolled children had no claims for thyroid-stimulating hormone testing within the next 180 days (P = .01)., Conclusions: Nearly one-third of children with suspected congenital hypothyroidism discontinued L-T4 by 3 years and fewer Medicaid-enrolled than privately insured children received timely follow-up thyroid-stimulating hormone testing. Future studies are indicated to understand the quality of care and developmental outcomes for children with congenital hypothyroidism and barriers to guideline adherence in evaluating for transient congenital hypothyroidism., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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13. Mapping the Relationship between Dysmorphology and Cognitive, Behavioral, and Developmental Outcomes in Children with Autism Spectrum Disorder.
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Tian LH, Wiggins LD, Schieve LA, Yeargin-Allsopp M, Dietz P, Aylsworth AS, Elias ER, Hoover-Fong JE, Meeks NJL, Souders MC, Tsai AC, Zackai EH, Alexander AA, Dowling NF, and Shapira SK
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- Child, Preschool, Cognition, Female, Humans, Male, Autism Spectrum Disorder complications, Intellectual Disability, Premature Birth
- Abstract
Previous studies investigating the association between dysmorphology and cognitive, behavioral, and developmental outcomes among individuals with autism spectrum disorder (ASD) have been limited by the binary classification of dysmorphology and lack of comparison groups. We assessed the association using a continuous measure of dysmorphology severity (DS) in preschool children aged 2-5 years (322 with ASD and intellectual disability [ID], 188 with ASD without ID, and 371 without ASD from the general population [POP]). In bivariate analyses, an inverse association between DS and expressive language, receptive language, fine motor, and visual reception skills was observed in children with ASD and ID. An inverse association of DS with fine motor and visual reception skills, but not expressive language and receptive language, was found in children with ASD without ID. No associations were observed in POP children. These results persisted after exclusion of children with known genetic syndromes or major morphologic anomalies. Quantile regression models showed that the inverse relationships remained significant after adjustment for sex, race/ethnicity, maternal education, family income, study site, and preterm birth. DS was not associated with autistic traits or autism symptom severity, behaviors, or regression among children with ASD with or without ID. Thus, DS was associated with a global impairment of cognitive functioning in children with ASD and ID, but only with fine motor and visual reception deficits in children with ASD without ID. A better understanding is needed for mechanisms that explain the association between DS and cognitive impairment in children with different disorders. Autism Res 2020, 13: 1227-1238. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We examined whether having more dysmorphic features (DFs) was related to developmental problems among children with autism spectrum disorder (ASD) with or without intellectual disability (ID), and children without ASD from the general population (POP). Children with ASD and ID had more language, movement, and learning issues as the number of DFs increased. Children with ASD without ID had more movement and learning issues as the number of DFs increased. These relationships were not observed in the POP group. Implications are discussed., (© 2020 International Society for Autism Research, Wiley Periodicals, Inc.)
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- 2020
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14. ADHD Medication Use During Pregnancy and Risk for Selected Birth Defects: National Birth Defects Prevention Study, 1998-2011.
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Anderson KN, Dutton AC, Broussard CS, Farr SL, Lind JN, Visser SN, Ailes EC, Shapira SK, Reefhuis J, and Tinker SC
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- Case-Control Studies, Female, Humans, Infant, Mothers, Odds Ratio, Pregnancy, Risk Factors, Attention Deficit Disorder with Hyperactivity drug therapy, Attention Deficit Disorder with Hyperactivity epidemiology, Gastroschisis
- Abstract
Objective: The objective of this study was to examine the prevalence of, and maternal characteristics associated with, ADHD medication use before and during pregnancy, and associations between early pregnancy ADHD medication use and risk for 12 selected birth defects. Method: We used data from the National Birth Defects Prevention Study (1998-2011), a U.S. population-based case-control study examining risk factors for major structural birth defects. Results: There was an increase in ADHD medication use from 1998-1999 (0.2%) to 2010-2011 (0.5%; p < .001). Early pregnancy ADHD medication use was more commonly reported by mothers of infants/fetuses with gastroschisis (crude odds ratio [cOR]: 2.9, 95% confidence interval [CI] = [1.2, 6.9]), omphalocele (cOR: 4.0, 95% CI = [1.2, 13.6]), and transverse limb deficiency (cOR: 3.3, 95% CI = [1.1, 9.6]). Conclusion: ADHD medication use before and during pregnancy was rare, but the prevalence of use has increased over time. In this analysis, early pregnancy ADHD medication use was associated with three of 12 selected birth defects.
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- 2020
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15. Exome sequencing of family trios from the National Birth Defects Prevention Study: Tapping into a rich resource of genetic and environmental data.
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Jenkins MM, Almli LM, Pangilinan F, Chong JX, Blue EE, Shapira SK, White J, McGoldrick D, Smith JD, Mullikin JC, Bean CJ, Nembhard WN, Lou XY, Shaw GM, Romitti PA, Keppler-Noreuil K, Yazdy MM, Kay DM, Carter TC, Olshan AF, Moore KJ, Nascone-Yoder N, Finnell RH, Lupo PJ, Feldkamp ML, Nickerson DA, Bamshad MJ, Brody LC, and Reefhuis J
- Subjects
- Family, Humans, Congenital Abnormalities genetics, Congenital Abnormalities prevention & control, Gene-Environment Interaction, Exome Sequencing
- Abstract
Background: The National Birth Defects Prevention Study (NBDPS) is a multisite, population-based, case-control study of genetic and nongenetic risk factors for major structural birth defects. Eligible women had a pregnancy affected by a birth defect or a liveborn child without a birth defect between 1997 and 2011. They were invited to complete a telephone interview to collect pregnancy exposure data and were mailed buccal cell collection kits to collect specimens from themselves, their child (if living), and their child's father. Over 23,000 families representing more than 30 major structural birth defects provided DNA specimens., Methods: To evaluate their utility for exome sequencing (ES), specimens from 20 children with colonic atresia were studied. Evaluations were conducted on specimens collected using cytobrushes stored and transported in open versus closed packaging, on native genomic DNA (gDNA) versus whole genome amplified (WGA) products and on a library preparation protocol adapted to low amounts of DNA., Results: The DNA extracted from brushes in open packaging yielded higher quality sequence data than DNA from brushes in closed packaging. Quality metrics of sequenced gDNA were consistently higher than metrics from corresponding WGA products and were consistently high when using a low input protocol., Conclusions: This proof-of-principle study established conditions under which ES can be applied to NBDPS specimens. Successful sequencing of exomes from well-characterized NBDPS families indicated that this unique collection can be used to investigate the roles of genetic variation and gene-environment interaction effects in birth defect etiologies, providing a valuable resource for birth defect researchers., (© 2019 Wiley Periodicals, Inc.)
- Published
- 2019
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16. A Novel Approach to Dysmorphology to Enhance the Phenotypic Classification of Autism Spectrum Disorder in the Study to Explore Early Development.
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Shapira SK, Tian LH, Aylsworth AS, Elias ER, Hoover-Fong JE, Meeks NJL, Souders MC, Tsai AC, Zackai EH, Alexander AA, Yeargin-Allsopp M, and Schieve LA
- Subjects
- Autism Spectrum Disorder classification, Autism Spectrum Disorder complications, Child, Child Development, Child, Preschool, Ethnicity, Female, Humans, Male, Autism Spectrum Disorder diagnosis, Craniofacial Abnormalities complications, Facies, Phenotype
- Abstract
The presence of multiple dysmorphic features in some children with autism spectrum disorder (ASD) might identify distinct ASD phenotypes and serve as potential markers for understanding causes and prognoses. To evaluate dysmorphology in ASD, children aged 3-6 years with ASD and non-ASD population controls (POP) from the Study to Explore Early Development were evaluated using a novel, systematic dysmorphology review approach. Separate analyses were conducted for non-Hispanic White, non-Hispanic Black, and Hispanic children. In each racial/ethnic group, ~ 17% of ASD cases were Dysmorphic compared with ~ 5% of POP controls. The ASD-POP differential was not explained by known genetic disorders or birth defects. In future epidemiologic studies, subgrouping ASD cases as Dysmorphic vs. Non-dysmorphic might help delineate risk factors for ASD.
- Published
- 2019
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17. Relationship of Weight Outcomes, Co-Occurring Conditions, and Severity of Autism Spectrum Disorder in the Study to Explore Early Development.
- Author
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Levy SE, Pinto-Martin JA, Bradley CB, Chittams J, Johnson SL, Pandey J, Pomykacz A, Ramirez A, Reynolds A, Rubenstein E, Schieve LA, Shapira SK, Thompson A, Young L, and Kral TVE
- Subjects
- Autism Spectrum Disorder diagnosis, Child Development Disorders, Pervasive diagnosis, Child, Preschool, Comorbidity, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Male, Prevalence, Retrospective Studies, Severity of Illness Index, United States epidemiology, Autism Spectrum Disorder epidemiology, Body Weight, Child Development, Child Development Disorders, Pervasive epidemiology, Population Surveillance methods
- Abstract
Objective: To assess contributing factors to increased obesity risk, by comparing children with autism spectrum disorder (ASD), developmental delays/disorders, and general population controls in weight status, and to examine associations between weight status and presence of co-occurring medical, behavioral, developmental, or psychiatric conditions across groups and ASD severity among children with ASD., Study Design: The Study to Explore Early Development is a multisite cross-sectional study of children, 2-5 years of age, classified as children with ASD (n = 668), children with developmental delays/disorders (n = 914), or general population controls (n = 884). Using an observational cohort design, we compared the 3 groups. Children's heights and weights were measured during a clinical visit. Co-occurring conditions (medical, behavioral, developmental/psychiatric) were derived from medical records, interviews, and questionnaires. ASD severity was measured by the Ohio State University Global Severity Scale for Autism., Results: The odds of overweight/obesity were 1.57 times (95% CI 1.24-2.00) higher in children with ASD than general population controls and 1.38 times (95% CI 1.10-1.72) higher in children with developmental delays/disorders than general population controls. The aORs were elevated for children with ASD after controlling for child co-occurring conditions (ASD vs general population controls: aOR = 1.51; 95% CI 1.14-2.00). Among children with ASD, those with severe ASD symptoms were 1.7 times (95% CI 1.1-2.8) more likely to be classified as overweight/obese compared with children with mild ASD symptoms., Conclusions: Prevention of excess weight gain in children with ASD, especially those with severe symptoms, and in children with developmental delays/disorders represents an important target for intervention., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2019
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18. Detecting moderate or complex congenital heart defects in adults from an electronic health records system.
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Diallo AO, Krishnaswamy A, Shapira SK, Oster ME, George MG, Adams JC, Walker ER, Weiss P, Ali MK, and Book W
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- Adult, Age Factors, Biomarkers, Case-Control Studies, Female, Humans, Logistic Models, Male, Middle Aged, ROC Curve, Risk, Sex Factors, Young Adult, Algorithms, Electrocardiography, Electronic Health Records, Heart Defects, Congenital diagnosis
- Abstract
Background: The prevalence of moderate or complex (moderate-complex) congenital heart defects (CHDs) among adults is increasing due to improved survival, but many patients experience lapses in specialty care or their CHDs are undocumented in the medical system. There is, to date, no efficient approach to identify this population., Objective: To develop and assess the performance of a risk score to identify adults aged 20-60 years with undocumented specific moderate-complex CHDs from electronic health records (EHR)., Methods: We used a case-control study (596 adults with specific moderate-complex CHDs and 2384 controls). We extracted age, race/ethnicity, electrocardiogram (EKG), and blood tests from routine outpatient visits (1/2009 through 12/2012). We used multivariable logistic regression models and a split-sample (4: 1 ratio) approach to develop and internally validate the risk score, respectively. We generated receiver operating characteristic (ROC) c-statistics and Brier scores to assess the ability of models to predict the presence of specific moderate-complex CHDs., Results: Out of six models, the non-blood biomarker model that included age, sex, and EKG parameters offered a high ROC c-statistic of 0.96 [95% confidence interval: 0.95, 0.97] and low Brier score (0.05) relative to the other models. The adult moderate-complex congenital heart defect risk score demonstrated good accuracy with 96.4% sensitivity and 80.0% specificity at a threshold score of 10., Conclusions: A simple risk score based on age, sex, and EKG parameters offers early proof of concept and may help accurately identify adults with specific moderate-complex CHDs from routine EHR systems who may benefit from specialty care.
- Published
- 2018
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19. Identification of Primary Congenital Hypothyroidism Based on Two Newborn Screens - Utah, 2010-2016.
- Author
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Jones DE, Hart K, Shapira SK, Murray M, Atkinson-Dunn R, and Rohrwasser A
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- Congenital Hypothyroidism epidemiology, Humans, Infant, Newborn, Retrospective Studies, Sensitivity and Specificity, Utah epidemiology, Congenital Hypothyroidism diagnosis, Neonatal Screening methods
- Abstract
Newborn screening for primary congenital hypothyroidism is part of the U.S. Recommended Uniform Screening Panel (1,2). Untreated congenital hypothyroidism can result in cognitive impairment and growth complications (decreased height/length). Initial newborn screening for congenital hypothyroidism is typically performed 24-48 hours after birth. Fourteen states, including Utah, perform a routine second screen at approximately 2 weeks of age.* During 2010-2016, a total of 359,432 infants in Utah were screened for congenital hypothyroidism, and 130 cases were diagnosed; among these, 98 had an abnormal first screen, and 25 had an abnormal second screen (seven infants were excluded because of missing data). A retrospective examination of Utah's screening data indicated that 20% of congenital hypothyroidism cases could not have been efficiently identified by a single screen alone. This study highlights the utility of a two-screen process and demonstrates that differential cutoff values for the first and second screens could optimize both screening sensitivity and specificity., Competing Interests: No conflicts of interest were reported.
- Published
- 2018
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20. Associations Between the 2nd to 4th Digit Ratio and Autism Spectrum Disorder in Population-Based Samples of Boys and Girls: Findings from the Study to Explore Early Development.
- Author
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Schieve LA, Tian L, Dowling N, Croen L, Hoover-Fong J, Alexander A, and Shapira SK
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- Child, Female, Humans, Male, Sex Factors, Autism Spectrum Disorder epidemiology, Fingers growth & development
- Abstract
The ratio of the index (2nd) finger to ring (4th) finger lengths (2D:4D) is a proxy for fetal testosterone and estradiol. Studies suggesting 2D:4D is inversely associated with autism spectrum disorder (ASD) in males were limited by lack of confounder and subgroup assessments. Studies of females are sparse. We examined associations between ASD and 2D:4D among children in the Study to Explore Early Development; we considered case subgroups and numerous potential demographic and maternal-perinatal health confounders. We observed a modest inverse association between ASD and right-hand 2D:4D in males; subgroup analyses indicated associations were limited to ASD cases with birth defects/genetic syndromes or dysmorphic features. We observed a positive association between ASD and left-hand 2D:4D in females, overall and within most case subgroups.
- Published
- 2018
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21. Invited Commentary: Male Reproductive System Congenital Malformations and the Risk of Autism Spectrum Disorder.
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Schieve LA and Shapira SK
- Subjects
- Child, Developmental Disabilities, Female, Genitalia, Male, Humans, Male, Pregnancy, Prevalence, Risk Factors, Autism Spectrum Disorder
- Abstract
Autism spectrum disorder (ASD) is a prevalent developmental disorder. Studies indicate that while ASD etiology has a genetic component, the risk is polygenic, with gene-environment interactions being likely. The prenatal period is a critical exposure window for nongenetic risk factors. Previous studies have found positive associations between congenital malformations (all types) and ASD; a few also found specific associations between genitourinary system malformations and ASD; and one study found an association between hypospadias and ASD. In the accompanying article, Rotem et al. (Am J Epidemiol. 2018;187(4):656-663) describe how they conducted a comprehensive analysis focusing on the shared risk of ASD with hypospadias or cryptorchidism, using existing data from a large Israeli health services system, which afforded several advantages because of the large sample size and low attrition of the patient population. The authors conducted a careful analysis, including sensitivity analyses, to account for risk factor and case misclassifications that might have occurred had they relied solely on preexisting diagnostic codes to define exposures and outcome. They observed positive associations between both hypospadias and cryptorchidism and ASD that were independent of numerous sociodemographic and pregnancy health factors. This study advances our understanding of ASD etiology and illustrates how existing data might be used to assess some ASD risk factors.
- Published
- 2018
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22. Treated Prevalence of Attention-Deficit/Hyperactivity Disorder Increased from 2009 to 2015 Among School-Aged Children and Adolescents in the United States.
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Nyarko KA, Grosse SD, Danielson ML, Holbrook JR, Visser SN, and Shapira SK
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- Adolescent, Child, Databases, Factual, Humans, Longitudinal Studies, Prevalence, United States, Attention Deficit Disorder with Hyperactivity drug therapy, Health Benefit Plans, Employee statistics & numerical data, Medicaid statistics & numerical data, Practice Patterns, Physicians' statistics & numerical data
- Abstract
Objectives: The purpose of this brief is to describe changes in the treated prevalence of medically managed attention-deficit/hyperactivity disorder (ADHD) among insured school-aged children and adolescents in the United States from 2009 to 2015. We examine the differences between those with employer-sponsored insurance (ESI) and with Medicaid insurance., Methods: We utilized two large longitudinal administrative datasets containing medical and drug claims data on individuals with ESI and Medicaid insurance from Truven Health MarketScan
® Administrative Claims Databases. Treated prevalence was measured as the percentage of school-aged children and adolescents enrolled in a calendar year who met the criteria for medically managed ADHD in the same calendar year. Subjects were eligible for inclusion if they were aged 6-17 years and were continuously enrolled during a calendar year., Results: The annual prevalence of treated ADHD among school-aged children and adolescents with ESI increased from 4.5% in 2009 to 6.7% in 2015. Among those with Medicaid it increased from 11.3% in 2009 to 13.3% in 2012, and fell after 2012, remaining steady from 2013 through 2015., Conclusion: Treated prevalence of ADHD increased continuously over time among school-aged children and adolescents with ESI, but declined slightly after 2012 among those in the Medicaid sample.- Published
- 2017
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- View/download PDF
23. CDC Grand Rounds: Newborn Screening for Hearing Loss and Critical Congenital Heart Disease.
- Author
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Grosse SD, Riehle-Colarusso T, Gaffney M, Mason CA, Shapira SK, Sontag MK, Braun KVN, and Iskander J
- Subjects
- Centers for Disease Control and Prevention, U.S., Early Diagnosis, Humans, Infant, Newborn, Program Evaluation, United States, Hearing Loss diagnosis, Heart Defects, Congenital diagnosis, Neonatal Screening methods, Point-of-Care Systems
- Abstract
Newborn screening is a public health program that benefits 4 million U.S. infants every year by enabling early detection of serious conditions, thus affording the opportunity for timely intervention to optimize outcomes (1). States and other U.S. jurisdictions decide whether and how to regulate newborn screening practices. Most newborn screening is done through laboratory analyses of dried bloodspot specimens collected from newborns. Point-of-care newborn screening is typically performed before discharge from the birthing facility. The Recommended Uniform Screening Panel includes two point-of-care conditions for newborn screening: hearing loss and critical congenital heart disease (CCHD). The objectives of point-of-care screening for these two conditions are early identification and intervention to improve neurodevelopment, most notably language and related skills among infants with permanent hearing loss, and to prevent death or severe disability resulting from delayed diagnosis of CCHD. Universal screening for hearing loss using otoacoustic emissions or automated auditory brainstem response was endorsed by the Joint Committee on Infant Hearing in 2000 and 2007* and was incorporated in the first Recommended Uniform Screening Panel in 2005. Screening for CCHD using pulse oximetry was recommended by the Advisory Committee on Heritable Disorders in Newborns and Children in 2010 based on an evidence review
† and was added to the Recommended Uniform Screening Panel in 2011.§ .- Published
- 2017
- Full Text
- View/download PDF
24. Survival Disparities Associated with Congenital Diaphragmatic Hernia.
- Author
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Hinton CF, Siffel C, Correa A, and Shapira SK
- Subjects
- Abnormalities, Multiple mortality, Black or African American, Female, Georgia, Hernias, Diaphragmatic, Congenital epidemiology, Hernias, Diaphragmatic, Congenital physiopathology, Hernias, Diaphragmatic, Congenital therapy, Humans, Infant, Infant, Newborn, Male, Parturition, Pregnancy, Risk Factors, Socioeconomic Factors, Survival Rate, White People, Hernias, Diaphragmatic, Congenital mortality
- Abstract
Background: We assessed sociodemographic and clinical factors that are associated with survival among infants with congenital diaphragmatic hernia (CDH)., Methods: Using data from the Metropolitan Atlanta Congenital Defects Program, we ascertained 150 infants born with CDH between 1979 and 2003 and followed via linkage with state vital records and the National Death Index. Kaplan-Meier survival probabilities and adjusted hazard ratios (HRs) were calculated for socioeconomic and clinical characteristics., Results: Survival increased from 40 to 62% over the study period. White infants born before 1988 were 2.9 times less likely to survive than those born after 1988. Black infants' survival did not show significant improvement after 1988. White infants' survival was not significantly affected by poverty, whereas black infants born in higher levels of poverty were 2.7 times less likely to survive than black infants born in lower levels of neighborhood poverty. White infants with multiple major birth defects were 2.6 times less likely to survive than those with CDH alone. The presence of multiple defects was not significantly associated with survival among black infants., Conclusions: Survival among infants and children with CDH has improved over time among whites, but not among blacks. Poverty is associated with lower survival among blacks, but not among whites. The presence of multiple defects is associated with lower survival among whites, but not among blacks. The differential effects of poverty and race should be taken into account when studying disparities in health outcomes. Birth Defects Research 109:816-823, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
- Full Text
- View/download PDF
25. Primary Care Provider Management of Congenital Hypothyroidism Identified Through Newborn Screening.
- Author
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Rosenthal NA, Bezar E, Mann S, Bachrach LK, Banerjee S, Geffner ME, Gottschalk M, Shapira SK, Hasegawa L, and Feuchtbaum L
- Abstract
Objective: To assess Primary Congenital Hypothyroidism (CH) management patterns and feasibility of providing long-term care for patients with CH identified through newborn screening by Primary Care Providers (PCPs) in California and Hawaii., Study Design: A survey was mailed to all physicians (N=823) listed as the referral doctor for confirmed patients with CH identified through newborn screening programs in both states between 01/01/2009-12/31/2013. Information was collected on CH management patterns, barriers to providing care, and knowledge on CH treatment. Descriptive statistics and bivariate logistic regression results were reported., Results: 206 PCPs completed the survey. Among these, 78% currently have patients with CH and 91% indicated willingness to provide long-term care to new patients with CH. Among PCPs currently caring for patients with CH, 17% managed CH by themselves with limited assistance from endocrinologists; 63% were involved in managing CH but endocrinologists played a larger role than PCPs; 19% were not involved in CH care. Only 49% of PCPs correctly answered questions regarding recommended follow-up frequencies and 23% knew the correct age for a trial off levothyroxine for suspected transient CH. Top two perceived barriers to providing long-term care included "need guidance or support from endocrinologists" (61%) and "not familiar with CH treatment guidelines" (28%)., Conclusion: The majority of PCPs surveyed are willing to provide long-term care to patients with CH, but need support from endocrinologists and increased knowledge about current treatment guidelines.
- Published
- 2017
26. Single newborn screen or routine second screening for primary congenital hypothyroidism.
- Author
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Shapira SK, Hinton CF, Held PK, Jones E, Harry Hannon W, and Ojodu J
- Subjects
- Algorithms, Congenital Hypothyroidism ethnology, Humans, Infant, Newborn, Retrospective Studies, United States epidemiology, Congenital Hypothyroidism diagnosis, Congenital Hypothyroidism epidemiology, Neonatal Screening methods
- Abstract
Routine second screening of most newborns at 8-14 days of life for a panel of newborn conditions occurs in 12 U.S. states, while newborns in the other states typically undergo only a single routine newborn screen. The study objective was to evaluate screening consequences for primary congenital hypothyroidism (CH) in one- and two-screen states according to laboratory practices and medical or biochemical characteristics of screen-positive cases. Individual-level medical and biochemical data were retrospectively collected and analyzed for 2251 primary CH cases in one-screen (CA, WI) and two-screen (AL, DE, MD, OR, TX) states. Aggregate data were collected and analyzed for medical and biochemical characteristics of all screened newborns in the states. Among the states evaluated in this study, the detection rate of primary CH was higher in the one-screen states. In the two-screen states, 11.5% of cases were detected on the second screen. In multivariate analyses, only race/ethnicity was a significant predictor of cases identified on the first versus second screen, which likely reflects a physiologic difference in primary CH presentation. Newborn screening programs must heed the potential for newborns with CH not being detected by a single screen, particularly newborns of certain races/ethnicities. If the two-screen states converted to a single screen using their current algorithms, newborns currently identified on the routine second screen would presumably not be detected, resulting in probable delayed diagnosis and treatment. However, based on the one-screen state experiences, with appropriate modifications in screening method and algorithm, the two-screen states might convert to single screen operation for CH without loss in performance., (Published by Elsevier Inc.)
- Published
- 2015
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- View/download PDF
27. Congenital adrenal hyperplasia cases identified by newborn screening in one- and two-screen states.
- Author
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Held PK, Shapira SK, Hinton CF, Jones E, Hannon WH, and Ojodu J
- Subjects
- Algorithms, Female, Humans, Infant, Infant, Newborn, Male, Retrospective Studies, United States epidemiology, Adrenal Hyperplasia, Congenital diagnosis, Adrenal Hyperplasia, Congenital epidemiology, Neonatal Screening methods
- Abstract
There is no clear consensus among state newborn screening programs on whether routine second screening of newborns identifies clinically relevant cases of congenital adrenal hyperplasia. This retrospective study evaluated laboratory practices, along with biochemical and medical characteristics of congenital adrenal hyperplasia (CAH) cases (1) detected on the first newborn screen in one-screen compared to two-screen states, and (2) detected on the first versus the second screen in the two-screen states, to determine the effectiveness of a second screen. A total of 374 confirmed cases of CAH from 2 one-screen states and 5 two-screen states were included in this study. Demographic data and diagnostic information on each reported case were collected and analyzed. Additionally, laboratory data, including screening methodologies and algorithms, were evaluated. The one-screen states reported 99 cases of CAH out of 1,740,586 (1 in 17,500) newborns screened: 88 (89%) identified on the first screen and 5 (5%) identified on the targeted second screen. The two-screen states reported 275 cases of CAH out of 2,629,627 (1 in 9500) newborns screened: 165 (60%) identified on the first screen and 99 (36%) identified on the second screen. Using a multivariate model, the only significant predictor of whether a case was identified on the first or the second screen in the two-screen states was the type of CAH. Compared with classical salt-wasting CAH, classical simple virilizing and non-classical CAH cases were less likely to be detected on the first versus the second screen. The routine second newborn screen is important for identifying children with CAH, particularly simple virilizing and non-classical forms, which might otherwise not be captured through a single screen., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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28. The National Birth Defects Prevention Study: A review of the methods.
- Author
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Reefhuis J, Gilboa SM, Anderka M, Browne ML, Feldkamp ML, Hobbs CA, Jenkins MM, Langlois PH, Newsome KB, Olshan AF, Romitti PA, Shapira SK, Shaw GM, Tinker SC, and Honein MA
- Subjects
- Congenital Abnormalities epidemiology, Female, Genetic Predisposition to Disease, Humans, Infant, Newborn, United States epidemiology, Congenital Abnormalities prevention & control, Data Collection methods, Genetic Markers, Neonatal Screening methods, Population Surveillance methods
- Abstract
Background: The National Birth Defects Prevention Study (NBDPS) is a large population-based multicenter case-control study of major birth defects in the United States., Methods: Data collection took place from 1998 through 2013 on pregnancies ending between October 1997 and December 2011. Cases could be live born, stillborn, or induced terminations, and were identified from birth defects surveillance programs in Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah. Controls were live born infants without major birth defects identified from the same geographical regions and time periods as cases by means of either vital records or birth hospitals. Computer-assisted telephone interviews were completed with women between 6 weeks and 24 months after the estimated date of delivery. After completion of interviews, families received buccal cell collection kits for the mother, father, and infant (if living)., Results: There were 47,832 eligible cases and 18,272 eligible controls. Among these, 32,187 (67%) and 11,814 (65%), respectively, provided interview information about their pregnancies. Buccal cell collection kits with a cytobrush for at least one family member were returned by 19,065 case and 6,211 control families (65% and 59% of those who were sent a kit). More than 500 projects have been proposed by the collaborators and over 200 manuscripts published using data from the NBDPS through December 2014., Conclusion: The NBDPS has made substantial contributions to the field of birth defects epidemiology through its rigorous design, including case classification, detailed questionnaire and specimen collection, large study population, and collaborative activities across Centers., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2015
- Full Text
- View/download PDF
29. What we don't know can hurt us: Nonresponse bias assessment in birth defects research.
- Author
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Strassle PD, Cassell CH, Shapira SK, Tinker SC, Meyer RE, and Grosse SD
- Subjects
- Humans, North Carolina, Bias, Cleft Lip, Cleft Palate
- Abstract
Background: Nonresponse bias assessment is an important and underutilized tool in survey research to assess potential bias due to incomplete participation. This study illustrates a nonresponse bias sensitivity assessment using a survey on perceived barriers to care for children with orofacial clefts in North Carolina., Methods: Children born in North Carolina between 2001 and 2004 with an orofacial cleft were eligible for inclusion. Vital statistics data, including maternal and child characteristics, were available on all eligible subjects. Missing 'responses' from nonparticipants were imputed using assumptions based on the distribution of responses, survey method (mail or phone), and participant maternal demographics., Results: Overall, 245 of 475 subjects (51.6%) responded to either a mail or phone survey. Cost as a barrier to care was reported by 25.0% of participants. When stratified by survey type, 28.3% of mail respondents and 17.2% of phone respondents reported cost as a barrier. Under various assumptions, the bias-adjusted estimated prevalence of cost as barrier to care ranged from 16.1% to 30.0%. Maternal age, education, race, and marital status at time of birth were not associated with subjects reporting cost as a barrier., Conclusion: As survey response rates continue to decline, the importance of assessing the potential impact of nonresponse bias has become more critical. Birth defects research is particularly conducive to nonresponse bias analysis, especially when birth defect registries and birth certificate records are used. Future birth defect studies which use population-based surveillance data and have incomplete participation could benefit from this type of nonresponse bias assessment. Birth Defects Research (Part A) 103:603-609, 2015. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2015
- Full Text
- View/download PDF
30. Rationale for periodic reporting on the use of selected clinical preventive services to improve the health of infants, children, and adolescents--United States.
- Author
-
Yeung LF, Shapira SK, Coates RJ, Shaw FE, Moore CA, Boyle CA, and Thacker SB
- Subjects
- Adolescent, Centers for Disease Control and Prevention, U.S., Child, Female, Humans, Infant, Male, United States, Adolescent Health Services statistics & numerical data, Child Health Services statistics & numerical data, Population Surveillance, Preventive Health Services statistics & numerical data
- Abstract
This supplement is the second of a series of periodic reports from a CDC initiative to monitor and report on the use of a set of selected clinical preventive services in the U.S. population in the context of recent national initiatives to improve access to and use of such services. Increasing the use of these services can result in substantial reductions in the burden of illness, death, and disability and lower treatment costs. This supplement focuses on services to improve the health of U.S. infants, children, and adolescents. The majority of clinical preventive services for infants, children, and adolescents are provided by the health-care sector. Public health agencies play important roles in increasing the use of these services by identifying and implementing policies that are effective in increasing use of the services and by collaborating with stakeholders to conduct programs to improve use. Recent health-reform initiatives, including efforts to increase the accessibility and affordability of preventive services, fund community prevention programs, and improve the use of health information technologies, offer opportunities to improve use of preventive services. This supplement, which follows a previous report on adult services, provides baseline information on the use of a set of selected clinical preventive services to improve the health of infants, children, and adolescents before implementation of these recent initiatives and discusses opportunities to increase the use of such services. This information can help public health practitioners, in collaboration with other stakeholders that have key roles in improving infant, child, and adolescent health (e.g., parents or guardians and their employers, health plans, health professionals, schools, child care facilities, community groups, and voluntary associations), understand the potential benefits of the recommended services, address the problem of underuse, and identify opportunities to apply effective strategies to improve use and foster accountability among stakeholders.
- Published
- 2014
31. Expanding diagnostic testing beyond cytogenetics: implications for birth defects research and surveillance.
- Author
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Jackson JM, Druschel CM, and Shapira SK
- Subjects
- Chromosomes, Human, Pair 22 genetics, Cytogenetics methods, Female, Humans, In Situ Hybridization, Fluorescence methods, Male, Chromosome Aberrations, Congenital Abnormalities diagnosis, Congenital Abnormalities epidemiology, Congenital Abnormalities genetics, Epidemiological Monitoring, Genetic Diseases, Inborn diagnosis, Genetic Diseases, Inborn epidemiology, Genetic Diseases, Inborn genetics
- Published
- 2013
- Full Text
- View/download PDF
32. The Study to Explore Early Development (SEED): a multisite epidemiologic study of autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) network.
- Author
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Schendel DE, Diguiseppi C, Croen LA, Fallin MD, Reed PL, Schieve LA, Wiggins LD, Daniels J, Grether J, Levy SE, Miller L, Newschaffer C, Pinto-Martin J, Robinson C, Windham GC, Alexander A, Aylsworth AS, Bernal P, Bonner JD, Blaskey L, Bradley C, Collins J, Ferretti CJ, Farzadegan H, Giarelli E, Harvey M, Hepburn S, Herr M, Kaparich K, Landa R, Lee LC, Levenseller B, Meyerer S, Rahbar MH, Ratchford A, Reynolds A, Rosenberg S, Rusyniak J, Shapira SK, Smith K, Souders M, Thompson PA, Young L, and Yeargin-Allsopp M
- Subjects
- Autistic Disorder etiology, Autistic Disorder psychology, Case-Control Studies, Child, Preschool, Developmental Disabilities etiology, Developmental Disabilities psychology, Female, Humans, Male, Parents, Phenotype, Prevalence, Surveys and Questionnaires, Autistic Disorder epidemiology, Developmental Disabilities epidemiology
- Abstract
The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal, gastrointestinal, and sociodemographic characteristics. SEED uses a case-control design with population-based ascertainment of children aged 2-5 years with an autism spectrum disorder (ASD) and children in two control groups-one from the general population and one with non-ASD developmental problems. Data from parent-completed questionnaires, interviews, clinical evaluations, biospecimen sampling, and medical record abstraction focus on the prenatal and early postnatal periods. SEED is a valuable resource for testing hypotheses regarding ASD characteristics and causes.
- Published
- 2012
- Full Text
- View/download PDF
33. Paternal occupation and birth defects: findings from the National Birth Defects Prevention Study.
- Author
-
Desrosiers TA, Herring AH, Shapira SK, Hooiveld M, Luben TJ, Herdt-Losavio ML, Lin S, and Olshan AF
- Subjects
- Adult, Bayes Theorem, Case-Control Studies, Congenital Abnormalities epidemiology, Humans, Infant, Newborn, Interviews as Topic, Logistic Models, Male, Prevalence, Risk Factors, Congenital Abnormalities etiology, Fathers, Occupational Exposure adverse effects, Occupations
- Abstract
Objectives: Several epidemiological studies have suggested that certain paternal occupations may be associated with an increased prevalence of birth defects in offspring. Using data from the National Birth Defects Prevention Study, the authors investigated the association between paternal occupation and birth defects in a case-control study of cases comprising over 60 different types of birth defects (n=9998) and non-malformed controls (n=4066) with dates of delivery between 1997 and 2004., Methods: Using paternal occupational histories reported by mothers via telephone interview, jobs were systematically classified into 63 groups based on shared exposure profiles within occupation and industry. Data were analysed using bayesian logistic regression with a hierarchical prior for dependent shrinkage to stabilise estimation with sparse data., Results: Several occupations were associated with an increased prevalence of various birth defect categories, including mathematical, physical and computer scientists; artists; photographers and photo processors; food service workers; landscapers and groundskeepers; hairdressers and cosmetologists; office and administrative support workers; sawmill workers; petroleum and gas workers; chemical workers; printers; material moving equipment operators; and motor vehicle operators., Conclusions: Findings from this study might be used to identify specific occupations worthy of further investigation and to generate hypotheses about chemical or physical exposures common to such occupations.
- Published
- 2012
- Full Text
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34. Evaluation of immunization rates and safety among children with inborn errors of metabolism.
- Author
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Klein NP, Aukes L, Lee J, Fireman B, Shapira SK, Slade B, Baxter R, and Summar M
- Subjects
- Adolescent, Age Factors, California, Case-Control Studies, Child, Child, Preschool, Databases, Factual, Emergency Service, Hospital statistics & numerical data, Female, Follow-Up Studies, Hospitalization statistics & numerical data, Humans, Immunization adverse effects, Immunization Schedule, Infant, Male, Reference Values, Retrospective Studies, Risk Assessment, Safety Management, Sex Factors, Time Factors, Vaccination adverse effects, Vaccination methods, Vaccines administration & dosage, Vaccines adverse effects, Communicable Disease Control, Immunization methods, Immunization statistics & numerical data, Metabolism, Inborn Errors diagnosis, Metabolism, Inborn Errors immunology
- Abstract
Background: Children with inherited metabolic disorders are a potential high-risk group for vaccine-preventable diseases, yet information regarding immunization rates and vaccine safety within this population is limited., Methods: Using Northern California Kaiser Permanente's electronic medical record, we identified children with inborn errors of metabolism from 1990 to 2007. We assessed immunization rates among infants with inborn errors of metabolism born at Northern California Kaiser Permanente matched to healthy infants (1 to 20), comparing both vaccines received by 2 years of age and age at vaccination. We assessed postvaccination adverse events among children up to 18 years old with inborn errors of metabolism, separately comparing emergency-department visits and hospitalizations during postvaccine days 0 to 30 (primary) and days 0 to 14 (secondary)., Results: Comparing infants with inborn errors of metabolism (n = 77) versus matched control subjects (n = 1540), similar proportions were up to date for vaccines at 2 years of age, and there was no evidence of delay in receipt of recommended vaccines during the first year. Vaccination of children with inborn errors of metabolism (n = 271) was not associated with any significant increase in emergency-department visits or hospitalizations during the 30 days after vaccination. Secondary analyses suggested that there may be increased rates of hospitalizations 2 weeks after vaccination for the sickest 1- to 4-year-old children., Conclusions: Children with inborn errors of metabolism at Northern California Kaiser Permanente received vaccines on the same immunization schedule as healthy infants. Immunization was not associated with increased risk for serious adverse events during the month after vaccination, providing overall reassurance that routine vaccination of children with inborn errors of metabolism does not result in adverse effects.
- Published
- 2011
- Full Text
- View/download PDF
35. Letter to the editor: Ventricular septal defects and the National Birth Defects Prevention Study.
- Author
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Rasmussen SA, Riehle-Colarusso T, Shapira SK, Honein MA, and Reefhuis J
- Subjects
- Congenital Abnormalities epidemiology, Congenital Abnormalities prevention & control, Female, Heart Septal Defects, Ventricular epidemiology, Heart Septal Defects, Ventricular prevention & control, Humans, Infant, Newborn, Population Surveillance methods, United States epidemiology, Centers for Disease Control and Prevention, U.S. classification, Congenital Abnormalities classification, Heart Septal Defects, Ventricular classification, Heart Septal Defects, Ventricular physiopathology
- Published
- 2011
- Full Text
- View/download PDF
36. Use of special education services among children with and without congenital gastrointestinal anomalies.
- Author
-
Hamrick SE, Strickland MJ, Shapira SK, Autry A, and Schendel D
- Subjects
- Adolescent, Child, Child, Preschool, Cohort Studies, Developmental Disabilities surgery, Female, Gastrointestinal Tract surgery, Georgia, Health Surveys, Humans, Infant, Infant, Newborn, Infant, Premature, Diseases epidemiology, Infant, Premature, Diseases surgery, Male, Odds Ratio, Pregnancy, Utilization Review statistics & numerical data, Developmental Disabilities epidemiology, Education, Special statistics & numerical data, Gastrointestinal Tract abnormalities
- Abstract
Our objective was to evaluate the relationship between congenital gastrointestinal anomalies requiring neonatal surgery and neurodevelopmental outcome. Among the children born in metropolitan Atlanta during 1982-2001 who survived to age 1 year (N = 762,824), we identified children with congenital gastrointestinal anomalies via linkage with the Metropolitan Atlanta Congenital Defects Program and children who received special education services via linkage with the Special Education Database of Metropolitan Atlanta. Several modest increases in special education service use were observed among children with isolated congenital gastrointestinal anomalies; no association was statistically significant. Among children with Hirschsprung disease, gastroschisis, esophageal atresia, intestinal malrotation, bowel atresia, or imperforate anus who had multiple anomalies, we observed statistically significant increases in special education service use.
- Published
- 2010
- Full Text
- View/download PDF
37. Future research directions to identify causes of the increasing incidence rate of congenital hypothyroidism in the United States.
- Author
-
Shapira SK, Lloyd-Puryear MA, and Boyle C
- Subjects
- Biomedical Research, Birth Weight, Congenital Hypothyroidism diagnosis, Congresses as Topic, Female, Humans, Incidence, Infant, Newborn, Neonatal Screening, Parity, Pregnancy, Premature Birth epidemiology, Risk Factors, Thyroid Function Tests, United States, Congenital Hypothyroidism epidemiology
- Abstract
A workshop to evaluate the reported increasing trend in the incidence rate of primary congenital hypothyroidism (CH) identified by newborn screening was held February 27 and 28, 2008, in Atlanta, Georgia, and was sponsored by the Centers for Disease Control and Prevention, the Health Resources and Services Administration, and the National Newborn Screening and Genetics Resource Center. Through a series of presentations and discussions, this group of experts considered a variety of factors that could be contributing to the perceived increasing trend of the CH-incidence rate, the gaps in knowledge that need to be overcome to identify the causes of the observed trend, and possible future research activities that might resolve the uncertainties surrounding the increasing incidence rate of CH in the United States. On the basis of these discussions, workshop participants concluded that the initial focus of future efforts should be to determine if the increasing CH-incidence rate persists once there is standardization of the diagnostic criteria for the classification of CH versus transient hypothyroidism. In discussions, workshop participants suggested that if the increasing incidence rate of CH could not be explained by definitional issues, then future research could focus on the identification and evaluation of risk factors for CH that might be changing among the US population and, thus, contributing to the observed increasing incidence rate of CH.
- Published
- 2010
- Full Text
- View/download PDF
38. Prevalence of developmental disabilities and receipt of special education services among children with an inborn error of metabolism.
- Author
-
Powell K, Van Naarden Braun K, Singh R, Shapira SK, Olney RS, and Yeargin-Allsopp M
- Subjects
- Child, Child, Preschool, Humans, Infant, Newborn, Metabolism, Inborn Errors diagnosis, Neonatal Screening, Developmental Disabilities complications, Education, Special, Metabolism, Inborn Errors complications
- Abstract
Objective: To examine the presence of developmental disabilities and receipt of special education services in children with an inborn error of metabolism., Study Design: The study population was children born from 1988 through 2001 in whom a metabolic disorder was diagnosed after identification by newborn screening (n = 97) or after clinical identification (n = 34). These children were linked to the Metropolitan Atlanta Development Disability Surveillance Program (MADDSP) and Special Education Database of Metropolitan Atlanta (SEDMA) to determine developmental outcomes at 8 years of age and 3 through 10 years of age, respectively. Medical and educational records were examined to consider factors contributing to developmental outcomes., Results: Of 97 children with a metabolic disorder identified with newborn screening, 12 (12.4%) were identified by SEDMA as receiving special education services and 2 (2.7%) were identified by MADDSP as having a developmental disability. Of the 34 children with a clinically identified metabolic disorder, 8 (23.5%) were identified with SEDMA, and 5 (17.2%) were identified with a MADDSP developmental disability., Conclusion: Early identification and treatment have been successful in limiting the impact of severe developmental disabilities. Continued surveillance and research are needed to monitor less severe developmental outcomes., (Copyright 2010 Mosby, Inc. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
39. Association of paternal age and risk for major congenital anomalies from the National Birth Defects Prevention Study, 1997 to 2004.
- Author
-
Green RF, Devine O, Crider KS, Olney RS, Archer N, Olshan AF, and Shapira SK
- Subjects
- Adult, Chromosome Aberrations, Congenital Abnormalities genetics, Congenital Abnormalities prevention & control, DNA Damage, Female, Humans, Infant, Newborn, Logistic Models, Male, Maternal Age, Odds Ratio, Registries, Risk Factors, Spermatozoa pathology, United States epidemiology, Young Adult, Congenital Abnormalities epidemiology, Paternal Age
- Abstract
Purpose: The objective of this study was to examine the associations between paternal age and birth defects of unknown etiologies while carefully controlling for maternal age., Methods: By using 1997 to 2004 data from the National Birth Defects Prevention Study, we fit logistic regression models with paternal and maternal age as continuous variables while adjusting for demographic and other factors., Results: Elevated odds ratios (ORs) for each year increase in paternal age were found for cleft palate (OR. 1.02, 95% confidence interval [95% CI], 1.00-1.04), diaphragmatic hernia (OR, 1.04; 95% CI, 1.02-1.06), right ventricular outflow tract obstruction (OR, 1.03; 95% CI, 1.01-1.04), and pulmonary valve stenosis (OR, 1.02, 95% CI, 1.01-1.04). At younger paternal ages, each year increase in paternal age correlated with increased odds of having offspring with encephalocele, cataract, esophageal atresia, anomalous pulmonary venous return, and coarctation of the aorta, but these increased odds were not observed at older paternal ages. The effect of paternal age was modified by maternal age for gastroschisis, omphalocele, spina bifida, all orofacial clefts, and septal heart defects., Conclusions: Our findings suggest that paternal age may be a risk factor for some multifactorial birth defects., (Published by Elsevier Inc.)
- Published
- 2010
- Full Text
- View/download PDF
40. Long-term speech and language developmental issues among children with Duarte galactosemia.
- Author
-
Powell KK, Van Naarden Braun K, Singh RH, Shapira SK, Olney RS, and Yeargin-Allsopp M
- Subjects
- Adolescent, Autistic Disorder diagnosis, Cerebral Palsy diagnosis, Child, Child, Preschool, Databases, Factual statistics & numerical data, Developmental Disabilities diagnosis, Education, Special methods, Galactosemias epidemiology, Georgia epidemiology, Hearing Loss diagnosis, Humans, Infant, Infant, Newborn, Language Development Disorders complications, Language Development Disorders diagnosis, Neonatal Screening, Population Surveillance, Speech Disorders complications, Speech Disorders diagnosis, Time Factors, Vision, Low diagnosis, Education, Special statistics & numerical data, Galactosemias complications, Language Development Disorders therapy, Speech Disorders therapy
- Abstract
Purpose: : There is limited information on long-term outcomes among children with Duarte galactosemia and controversy about treatment of this potentially benign condition. This study examined developmental disabilities and issues that required special education services within a population-based sample of children with Duarte galactosemia., Methods: : Children born between 1988 and 2001 who were diagnosed with Duarte galactosemia and resided in the five-county metropolitan Atlanta area at birth and from 3 to 10 years of age were linked to the (1) Metropolitan Atlanta Developmental Disabilities Surveillance Program, an ongoing, population-based surveillance system for selected developmental disabilities and (2) Special Education Database of Metropolitan Atlanta. Special education records were reviewed for children who linked. Clinical genetics records were reviewed to assess laboratory levels at the time of diagnosis and metabolic control during treatment., Results: : Of the 59 eligible children, none were found to have intellectual disability, cerebral palsy, hearing loss, vision impairment, or an autism spectrum disorder. However, five, 8.5% of 3 to 10 years or 15.2% of eligible 8 years, were identified as having received special education services, four of whom were confirmed with a speech or language disorder, or were receiving services for speech or language or both compared with 4.5% and 5.9% of children without Duarte galactosemia, respectively., Conclusions: : Despite galactose restriction until 1 year, select developmental issues associated with special education, specifically involving speech and language, have been found among some children with Duarte galactosemia.
- Published
- 2009
- Full Text
- View/download PDF
41. Maternal vasoactive exposures, amniotic bands, and terminal transverse limb defects.
- Author
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Werler MM, Bosco JL, and Shapira SK
- Subjects
- Adult, Amniotic Band Syndrome epidemiology, Amniotic Band Syndrome physiopathology, Case-Control Studies, Female, Humans, Infant, Newborn, Interviews as Topic, Limb Deformities, Congenital epidemiology, Limb Deformities, Congenital physiopathology, Pregnancy, Pregnancy Complications, Cardiovascular, Risk Factors, Young Adult, Amniotic Band Syndrome etiology, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Antihypertensive Agents adverse effects, Antihypertensive Agents therapeutic use, Limb Deformities, Congenital etiology, Maternal Exposure, Nasal Decongestants adverse effects, Nasal Decongestants therapeutic use, Smoking adverse effects
- Abstract
Background: Limb reduction deficiencies that are accompanied by amniotic bands (AB-Ls) and terminal transverse limb deficiencies (TLDs) have each been attributed to vascular disruption; for the former, however, it is not clear if amniotic bands are the primary cause of or are secondary to vascular disruption. If amniotic bands are secondary to vascular disruption, then a shared pathogenesis for each case group might be exhibited by similar risk factors., Methods: We evaluated maternal age, education, race/ethnicity, parity, pregnancy wantedness, and vasoactive exposures among 139 AB-L and 373 TLD cases, using interview data collected from mothers in 10 states by the National Birth Defects Prevention Study. Vasoactive exposures included maternal cigarette smoking and use of decongestants, nonsteroid anti-inflammatory drugs, and antihypertensive drugs in the periconceptional period., Results: Increased risk estimates were observed for Black mothers (OR 2.5; 95% CI: 1.5-4.1) and nulliparous mothers (2.1; 1.4-3.0) in relation to AB-L, while neither was associated with TLD. Hispanic women (1.4; 1.0-1.9) and those not wanting the pregnancy (1.5; 1.1-2.1) had increased risks of TLD, but not AB-L. Maternal cigarette smoking and aspirin use each increased the risk of AB-L, but not TLD; while decongestants and possibly antihypertensive medications increased the risk of TLD, but not AB-L., Conclusions: The lack of consistent findings for the two case groups suggests that AB-L and TLD may be distinct entities. The inconsistencies also suggest that these vasoactive exposures may not be markers for vascular disruption or that vascular disruption may not play a major role in the pathogenesis of these two types of limb deficiencies.
- Published
- 2009
- Full Text
- View/download PDF
42. Eight years experience with enzyme replacement therapy in two children and one adult with Pompe disease.
- Author
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van Capelle CI, Winkel LP, Hagemans ML, Shapira SK, Arts WF, van Doorn PA, Hop WC, Reuser AJ, and van der Ploeg AT
- Subjects
- Adolescent, Adult, Animals, CHO Cells drug effects, Child, Cricetinae, Cricetulus, Female, Glycogen Storage Disease Type II pathology, Humans, Longitudinal Studies, Male, Muscle, Skeletal drug effects, Muscle, Skeletal pathology, Treatment Outcome, Glycogen Storage Disease Type II drug therapy, alpha-Glucosidases therapeutic use
- Abstract
Pompe disease (type 2 glycogenosis, acid maltase deficiency) is a disorder affecting skeletal and cardiac muscle, caused by deficiency of acid alpha-glucosidase. In 2006 enzyme therapy with recombinant human alpha-glucosidase received marketing approval based on studies in infants. Results in older children and adults are awaited. Earlier we reported on the 3-year follow-up data of enzyme therapy in two adolescents and one adult. In the present study these patients were followed for another 5 years. Two severely affected patients, wheelchair and ventilator dependent, who had shown stabilization of pulmonary and muscle function in the first 3 years, maintained this stabilization over the 5-year extension period. In addition patients became more independent in daily life activities and quality of life improved. The third moderately affected patient had shown a remarkable improvement in muscle strength and regained the ability to walk over the first period. He showed further improvement of strength and reached normal values for age during the extension phase. The results indicate that both long-term follow-up and timing of treatment are important topics for future studies.
- Published
- 2008
- Full Text
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43. Genetic risks to the mother and the infant: assessment, counseling, and management.
- Author
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Shapira SK and Dolan S
- Subjects
- Adolescent, Adult, Age Factors, Female, Humans, Pregnancy, Risk Assessment, Risk Factors, Genetic Counseling, Genetic Diseases, Inborn therapy, Preconception Care, Pregnancy Complications genetics, Pregnancy Outcome genetics
- Published
- 2006
- Full Text
- View/download PDF
44. Enzyme replacement therapy in late-onset Pompe's disease: a three-year follow-up.
- Author
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Winkel LP, Van den Hout JM, Kamphoven JH, Disseldorp JA, Remmerswaal M, Arts WF, Loonen MC, Vulto AG, Van Doorn PA, De Jong G, Hop W, Smit GP, Shapira SK, Boer MA, van Diggelen OP, Reuser AJ, and Van der Ploeg AT
- Subjects
- Adolescent, Adult, Animals, Child, Female, Follow-Up Studies, Glycogen Storage Disease Type II enzymology, Glycogen Storage Disease Type II physiopathology, Humans, Linear Models, Male, Muscle, Skeletal drug effects, Muscle, Skeletal enzymology, Muscle, Skeletal pathology, Pilot Projects, Rabbits, Recombinant Proteins pharmacology, Recombinant Proteins therapeutic use, Recovery of Function drug effects, Recovery of Function physiology, alpha-Glucosidases pharmacology, Glycogen Storage Disease Type II drug therapy, alpha-Glucosidases therapeutic use
- Abstract
Pompe's disease is an autosomal recessive myopathy. The characteristic lysosomal storage of glycogen is caused by acid alpha-glucosidase deficiency. Patients with late-onset Pompe's disease present with progressive muscle weakness also affecting pulmonary function. In search of a treatment, we investigated the feasibility of enzyme replacement therapy with recombinant human alpha-glucosidase from rabbit milk. Three patients (aged 11, 16, and 32 years) were enrolled in the study. They were all wheelchair-bound and two of them were ventilator dependent with a history of deteriorating pulmonary function. After 3 years of treatment with weekly infusions of alpha-glucosidase, the patients had stabilized pulmonary function and reported less fatigue. The youngest and least affected patient showed an impressive improvement of skeletal muscle strength and function. After 72 weeks of treatment, he could walk without support and finally abandoned his wheelchair. Our findings demonstrate that recombinant human alpha-glucosidase from rabbit milk has a therapeutic effect in late-onset Pompe's disease. There is good reason to continue the development of enzyme replacement therapy for Pompe's disease and to explore further the production of human therapeutic proteins in the milk of mammals.
- Published
- 2004
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45. Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome.
- Author
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Heilstedt HA, Ballif BC, Howard LA, Lewis RA, Stal S, Kashork CD, Bacino CA, Shapira SK, and Shaffer LG
- Subjects
- Abnormalities, Multiple diagnosis, Adolescent, Child, Child, Preschool, Chromosome Disorders diagnosis, Facies, Female, Gene Deletion, Humans, Infant, Infant, Newborn, Male, Microsatellite Repeats, Monosomy diagnosis, Physical Chromosome Mapping, Syndrome, Abnormalities, Multiple genetics, Chromosome Breakage genetics, Chromosome Disorders genetics, Chromosomes, Human, Pair 1 genetics, Monosomy genetics
- Abstract
Monosomy 1p36 is the most common terminal deletion syndrome. This contiguous gene deletion syndrome is presumably caused by haploinsufficiency of a number of genes. We have constructed a contig of overlapping large-insert clones for the most distal 10.5 Mb of 1p36, evaluated the deletion sizes in 61 subjects with monosomy 1p36 from 60 families, and created a natural deletion panel. We found pure terminal deletions, interstitial deletions, derivative chromosomes, and more complex rearrangements. Breakpoints were "binned" into 0.5-Mb regions. Analyses revealed some clustering of breakpoints but no single common breakpoint. Determination of the parental origin showed that 60% of de novo 1p36 terminal deletions arose from the maternally inherited chromosome. Of the 61 subjects, 30 were examined systematically through a protocol at the Texas Children's Hospital General Clinical Research Center. Specifically, we report hearing evaluations, palatal and ophthalmological examinations, echocardiograms, neurological assessments, and thyroid function tests. To our knowledge, this systematic molecular and clinical characterization of monosomy 1p36 is the largest and most comprehensive study of this deletion syndrome to date. Many cytogenetically visible, apparent terminal deletions are more complex than anticipated by cytogenetics, as revealed at the molecular level by our study. Our clinical findings allow for the more accurate recognition of the syndrome and for proper medical evaluation.
- Published
- 2003
- Full Text
- View/download PDF
46. Familial complex chromosomal rearrangement resulting in a recombinant chromosome.
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Berend SA, Bodamer OA, Shapira SK, Shaffer LG, and Bacino CA
- Subjects
- Humans, In Situ Hybridization, Fluorescence, Infant, Newborn, Karyotyping, Male, Translocation, Genetic, Chromosome Aberrations, Chromosomes, Human, Pair 16 genetics, Chromosomes, Human, Pair 3 genetics, Chromosomes, Human, Pair 8 genetics
- Abstract
Familial complex chromosomal rearrangements (CCRs) are rare and tend to involve fewer breakpoints and fewer chromosomes than CCRs that are de novo in origin. We report on a CCR identified in a child with congenital heart disease and dysmorphic features. Initially, the child's karyotype was thought to involve a straightforward three-way translocation between chromosomes 3, 8, and 16. However, after analyzing the mother's chromosomes, the mother was found to have a more complex rearrangement that resulted in a recombinant chromosome in the child. The mother's karyotype included an inverted chromosome 2 and multiple translocations involving chromosomes 3, 5, 8, and 16. No evidence of deletion or duplication that could account for the clinical findings in the child was identified., (Copyright 2002 Wiley-Liss, Inc.)
- Published
- 2002
- Full Text
- View/download PDF
47. Loss of the potassium channel beta-subunit gene, KCNAB2, is associated with epilepsy in patients with 1p36 deletion syndrome.
- Author
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Heilstedt HA, Burgess DL, Anderson AE, Chedrawi A, Tharp B, Lee O, Kashork CD, Starkey DE, Wu YQ, Noebels JL, Shaffer LG, and Shapira SK
- Subjects
- Adolescent, Child, Child, Preschool, Craniofacial Abnormalities epidemiology, Craniofacial Abnormalities genetics, Electroencephalography, Epilepsy diagnosis, Epilepsy epidemiology, Humans, In Situ Hybridization, Fluorescence, Infant, Intellectual Disability epidemiology, Intellectual Disability genetics, Mutation genetics, Potassium Channels, Voltage-Gated genetics, Reverse Transcriptase Polymerase Chain Reaction, Chromosome Deletion, Chromosomes, Human, Pair 1 genetics, Epilepsy genetics, Potassium Channels genetics
- Abstract
Purpose: Clinical features associated with chromosome 1p36 deletion include characteristic craniofacial abnormalities, mental retardation, and epilepsy. The presence and severity of specific phenotypic features are likely to be correlated with loss of a distinct complement of genes in each patient. We hypothesize that hemizygous deletion of one, or a few, critical gene(s) controlling neuronal excitability is associated with the epilepsy phenotype. Because ion channels are important determinants of seizure susceptibility and the voltage-gated K(+) channel beta-subunit gene, KCNAB2, has been localized to 1p36, we propose that deletion of this gene may be associated with the epilepsy phenotype., Methods: Twenty-four patients were evaluated by fluorescence in situ hybridization with a probe containing KCNAB2. Clinical details were obtained by neurologic examination and EEG., Results: Nine patients are deleted for the KCNAB2 locus, and eight (89%) of these have epilepsy or epileptiform activity on EEG. The majority of patients have a severe seizure phenotype, including infantile spasms. In contrast, of those not deleted for KCNAB2, only 27% have chronic seizures, and none had infantile spasms., Conclusions: Lack of the beta subunit would be predicted to reduce K(+) channel-mediated membrane repolarization and increase neuronal excitability, suggesting a possible relation between loss of this gene and the development of seizures. Because some patients with seizures were not deleted for KCNAB2, there may be additional genes within 1p36 that contribute to epilepsy in this syndrome. Hemizygosity of this gene in a majority of monosomy 1p36 syndrome patients with epilepsy suggests that haploinsufficiency for KCNAB2 is a significant risk factor for epilepsy.
- Published
- 2001
- Full Text
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48. Mitochondrial DNA depletion associated with partial complex II and IV deficiencies and 3-methylglutaconic aciduria.
- Author
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Scaglia F, Sutton VR, Bodamer OA, Vogel H, Shapira SK, Naviaux RK, and Vladutiu GD
- Subjects
- Biopsy, Blotting, Southern, Child, Preschool, Humans, Infant, Male, Mitochondrial Encephalomyopathies complications, Muscle, Skeletal pathology, DNA, Mitochondrial analysis, Glutarates urine, Meglutol analogs & derivatives, Meglutol urine, Mitochondrial Encephalomyopathies genetics, Mitochondrial Encephalomyopathies urine
- Abstract
We report a patient with mitochondrial DNA depletion, partial complex II and IV deficiencies, and 3-methylglutaconic aciduria. Complex II deficiency has not been previously observed in mitochondrial DNA depletion syndromes. The observation of 3-methylglutaconic and 3-methylglutaric acidurias may be a useful indicator of a defect in respiratory chain function caused by mitochondrial DNA depletion.
- Published
- 2001
- Full Text
- View/download PDF
49. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO).
- Author
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Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, Shapira SK, Farndon PA, Wara DW, Emmal SA, and Ferguson BM
- Subjects
- Adolescent, Base Sequence, Child, Child, Preschool, DNA Mutational Analysis, Ectodermal Dysplasia complications, Exons genetics, Female, Genes, Recessive genetics, Genetic Linkage genetics, Humans, I-kappa B Kinase, Immunologic Deficiency Syndromes complications, Infant, Infant, Newborn, Male, NF-kappa B physiology, Pedigree, Protein Serine-Threonine Kinases chemistry, Protein Structure, Tertiary, Alleles, Ectodermal Dysplasia genetics, Immunologic Deficiency Syndromes genetics, Incontinentia Pigmenti genetics, Mutation genetics, Protein Serine-Threonine Kinases genetics, X Chromosome genetics
- Abstract
Hypohidrotic ectodermal dysplasia (HED), a congenital disorder of teeth, hair, and eccrine sweat glands, is usually inherited as an X-linked recessive trait, although rarer autosomal dominant and recessive forms exist. We have studied males from four families with HED and immunodeficiency (HED-ID), in which the disorder segregates as an X-linked recessive trait. Affected males manifest dysgammaglobulinemia and, despite therapy, have significant morbidity and mortality from recurrent infections. Recently, mutations in IKK-gamma (NEMO) have been shown to cause familial incontinentia pigmenti (IP). Unlike HED-ID, IP affects females and, with few exceptions, causes male prenatal lethality. IKK-gamma is required for the activation of the transcription factor known as "nuclear factor kappa B" and plays an important role in T and B cell function. We hypothesize that "milder" mutations at this locus may cause HED-ID. In all four families, sequence analysis reveals exon 10 mutations affecting the carboxy-terminal end of the IKK-gamma protein, a domain believed to connect the IKK signalsome complex to upstream activators. The findings define a new X-linked recessive immunodeficiency syndrome, distinct from other types of HED and immunodeficiency syndromes. The data provide further evidence that the development of ectodermal appendages is mediated through a tumor necrosis factor/tumor necrosis factor receptor-like signaling pathway, with the IKK signalsome complex playing a significant role.
- Published
- 2000
- Full Text
- View/download PDF
50. Monosomy 1p36.
- Author
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Slavotinek A, Shaffer LG, and Shapira SK
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Chromosome Disorders, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Syndrome, Chromosome Aberrations genetics, Chromosome Deletion, Chromosomes, Human, Pair 1 genetics
- Abstract
We have reviewed published reports on patients with segmental aneusomy for chromosome 1p36 to help geneticists and other health professionals in the recognition of this emerging chromosomal syndrome. Terminal deletions of the short arm of chromosome 1 are associated with hypotonia and developmental delay (usually severe), growth abnormalities (growth retardation, microcephaly, obesity), and craniofacial dysmorphism with a large anterior fontanelle, prominent forehead, deep set eyes, flat nasal bridge and midface hypoplasia, ear asymmetry, a pointed chin, and orofacial clefting. Minor cardiac malformations, cardiomyopathy, seizures, and ventricular dilatation are the more common additional findings. Sensorineural hearing loss and variable ophthalmological anomalies have also been frequently observed. Although the deletions can be detected by high resolution cytogenetic studies, confirmation by fluorescence in situ hybridisation is required in most cases. The majority of deletions are maternally derived. Molecular characterisation of 1p36 deletions has been undertaken in several cases, and it is likely that this condition is a contiguous gene deletion syndrome.
- Published
- 1999
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