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ObjectivesThe challenges of understanding how interventions influence follow-up medical care are magnified during genomic testing because few patients have received it to date and because the scope of information it provides is complex and often unexpected. We tested a novel strategy for quantifying downstream healthcare utilization after genomic testing to more comprehensively and efficiently identify related services. We also evaluated the effectiveness of different methods for collecting these data.MethodsWe developed a risk-based approach for a trial of newborn genomic sequencing in which we defined primary conditions based on existing diagnoses and family histories of disease and defined secondary conditions based on unexpected findings. We then created patient-specific lists of services associated with managing primary and secondary conditions. Services were quantified based on medical record reviews, surveys, and telephone check-ins with parents.ResultsBy focusing on services that genomic testing would most likely influence in the short-term, we reduced the number of services in our analyses by more than 90% compared with analyses of all observed services. We also identified the same services that were ordered in response to unexpected findings as were identified during expert review and by confirming whether recommendations were completed. Data also showed that quantifying healthcare utilization with surveys and telephone check-ins alone would have missed the majority of attributable services.ConclusionsOur risk-based strategy provides an improved approach for assessing the short-term impact of genomic testing and other interventions on healthcare utilization while conforming as much as possible to existing best-practice recommendations.

Although norm-referenced scores are essential to the identification of disability, they possess several features which affect their sensitivity to change. Norm-referenced scores often decrease over time among people with neurodevelopmental disorders who exhibit slower-than-average increases in ability. Further, the reliability of norm-referenced scores is lower at the tails of the distribution, resulting in floor effects and increased measurement error for people with neurodevelopmental disorders. In contrast, the person ability scores generated during the process of constructing a standardized test with item response theory are designed to assess change. We illustrate these limitations of norm-referenced scores, and relative advantages of ability scores, using data from studies of autism spectrum disorder and creatine transporter deficiency.

Mitochondrial fatty acid oxidation disorders include conditions in which the transport of activated acyl-Coenzyme A (CoA) into the mitochondria or utilization of these substrates is disrupted or blocked. This results in a deficit in the conversion of fat into energy. Most patients with fatty acid oxidation defects are now identified through newborn screening by tandem mass spectrometry. With earlier identification and preventative treatments, mortality and morbidity rates have improved. However, in the absence of severe health and neurological effects from these disorders, subtle developmental delays or neuropsychological deficits have been noted. Medical records were reviewed to identify outcomes in 85 children with FAOD's diagnosed through newborn screening and followed at one metabolic center. Overall, 54% of these children identified through newborn screening experienced developmental challenges. Speech delay or relative weakness in language was noted in 26 children (31%) and motor delays were noted in 24 children (29%). The majority of the 46 children receiving psychological evaluations performed well within the average range, with only 11% scoring less than 85 on developmental or intelligence tests. These results highlight the importance of screening children with fatty acid oxidation disorders to identify those with language, motor, or cognitive delay. Although expanded newborn screening dramatically changes the health and developmental outcomes in many children with fatty acid oxidation disorders, it also complicates the interpretation of biochemical and molecular findings and raises questions about the effectiveness or necessity of treatment in a large number of cases. Only by systematically evaluating developmental and neuropsychological outcomes using standardized methods will the true implications of newborn screening, laboratory results, and treatments for neurocognitive outcome in these disorders become clear. (Contains 7 tables and 2 figures.)

Background: Attribution theory, self-regulation, self-handicapping and sick role theories all suggest that children with chronic disease may be held to different standards. This study assesses child and parent attributions in pediatric chronic health conditions and addresses how attributional style may be related to treatment adherence. Methods: Four different vignettes were utilized to compare the attributional style of children with phenylketonuria (PKU) and parents of children with PKU to two comparison groups: children with other chronic medical conditions and medically healthy children. In addition, the relationship between metabolic control and attribution ratings was assessed in the PKU sample. Results: Parents of children with medical conditions provided attributions of less child control and more stability as well as more positive affective reactions when compared to parents of healthy children. Children without a medical condition viewed childhood problems as less controllable and more stable. Mothers were more disturbed affectively by behavioral dysregulation and fathers were more disturbed by academic difficulties. In the PKU sample, the higher the phenylalanine level in the child, the more likely the parent and child alike were to attribute childhood problems to external loci of control. Conclusions: Attributional styles appear not to be diagnosis-specific in pediatric populations. Attributional style may be an important variable to consider when targeting treatment adherence.

BACKGROUND. Newborn screening programs now identify children with >30 biochemical genetic disorders. False-positive identifications may increase as disorders are added to screening panels. Concerns arise regarding the potential impact on parental stress, family relationships, and perceptions of the child's health. METHODS. Parents of 173 infants with false-positive screening results for a biochemical genetic disorder in the expanded newborn screening panel were compared with parents of 67 children with normal screening results. Parents completed an interview that elicited information about demographic features, child and parental health, and understanding of newborn screening. Parents also completed the parenting stress index. RESULTS. Parents in the false-positive group attained higher total scores on the PSI than did parents in the normal-screened group, scoring higher on the parent-child dysfunction subscale and the difficult child subscale. Only approximately one third of parents in the false-positive group reported knowing the correct reason for repeat screening. Mothers who reported knowing the correct reason for their child's repeat screening test experienced less total stress than did mothers who were misinformed, were not informed, or did not remember. CONCLUSIONS. False-positive screening results may affect parental stress and the parent-child relationship. Improved communication with parents regarding the need for repeat screening tests may reduce the negative impact of false-positive results. Key Words newborn screening, false-positive, parental stress, vulnerable child, nocebo phenomenon, parent-child relationship Abbreviations PKU--phenylketonuria PSI--parenting stress index, RECENT EXPANSION OF newborn screening for biochemical genetic disorders has led not only to an increase in positive identifications but also to a dramatic increase in false-positive test results. A [...]

Objective. A major issue in maternal phenylketonuria (MPKU) has been whether maternal non-PKU mild hyperphenylalaninemia (MHP) is teratogenic. Such untreated pregnancies and their outcomes are presented on this report. Methods. Enrolled pregnancies in which the untreated prepregnancy assigned phenylalanine level (APL) was no more than 600 [micro]mol/L were included in the Maternal PKU Collaborative Study and were followed according to protocol. Results. Forty-eight enrolled women with non-PKU MHP had mean APL 408 [+ or -] 114 [micro]mol/L. They had a total of 58 pregnancies that resulted in live births. Fifty were untreated. Maternal phenylalanine (Phe) levels in the untreated pregnancies decreased during pregnancy for average Phe exposure of 270 [+ or -] 84 [micro]mol/L, virtually identical to the level of 269 [+ or -] 136 [micro]mol/L in the 8 treated pregnancies. Birth measurements in the 50 offspring from untreated pregnancies were within normal limits with z scores of -0,25 for weight, 0.28 for length, and -0.63 for head circumference, although birth head circumference was negatively correlated with maternal APL (r = -0.30). Only 1 offspring had congenital heart disease. Offspring IQ was 102 [+ or -] 15 compared with 96 [+ or -] 14 in the mothers with untreated pregnancies and with 109 [+ or -] 21 in control offspring. Conclusion. Maternal non-PKU MHP no more than 600 [micro]mol/L does not require dietary therapy. The naturally lower Phe level during pregnancy seems to protect against teratogenesis. Pediatrics 2003;112:1548-1552; maternal phenylalanine, genotype, offspring, birth weight, birth length, birth head circumference, IQ., Among teratogenic factors, maternal phenylketonuria (MPKU) is one of the most potent. More than 90% of the offspring from untreated pregnancies of women with classic PKU, ie, blood phenylalanine (Phe) [...]

Objective. To assess cognitive and behavioral outcome in treated maternal phenylketonuria (PKU) offspring. Methods. In this prospective, longitudinal study, 228 children who were born to mothers with treated PKU or untreated mild hyperphenylalaninemia were compared with 70 control subjects at 7 years of age. Results. Offspring cognitive outcome negatively correlated with the number of gestational weeks that elapsed until maternal metabolic control was achieved (r = -0.61). Behavioral outcome was similarly affected Postnatal measurement of stimulation in the home was also related to offspring IQ. Conclusions. Children who are born to mothers who have PKU and attain metabolic control before or very early in pregnancy seem to begin life with undiminished potential. Delay in attainment of maternal metabolic control is associated with declines in offspring developmental outcome. The postnatal environment also significantly affects outcome. Interventions to improve dietary compliance before and throughout pregnancy as well as interventions to improve the postnatal home environment may reduce the risks associated with maternal PKU. Pediatrics 2003;112:1544-1547; maternal phenylketonuria, maternal PKU, cognitive outcome, behavioral outcome., The present study includes school-age assessments of cognitive development, motor skills, expressive and receptive language, attention, daily living skills, achievement, emotional well-being, and behavior. Environmental influences such as prenatal exposure [...]

Expanded newborn screening for up to 20 different metabolic disorders may improve the health of children who test positive, according to a study of 258 children. However, children who have a false positive test may be hospitalized unnecessarily and their parents may be overly stressed. A false positive test means a diagnostic test is positive but the person who was tested doesn't really have the disease.

Maternal phenylketonuria (MPKU) is an increasingly common concern for health professionals involved in prenatal care. This single-participant study investigated the efficacy of prenatal psychotherapy in improving metabolic control, an important consideration in MPKU pregnancies. Results indicated a robust and positive relationship between psychotherapy and metabolic control. Levels of negative mood and levels of phenylalanine control were also strongly and positively correlated. Implications for treating MPKU are discussed, and prenatal psychotherapy is forwarded as a means of improving birth outcomes in this population.

All pregnant women should be screened for thyroid deficiency. Researchers measured the level of thyroid hormones in blood samples taken from pregnant women up to 10 years prior. Sixty-two women had low levels, a condition called hypothyroidism. Compared to 124 women who had normal levels during pregnancy, the 7- to 9-year-old children of the women with hypothyroidism scored lower on 15 tests of intelligence, language, reading ability, school performance and visual-motor performance. Nineteen percent had IQ scores of 85 or less.

Much emphasis has been placed on participant's psychological safety within genomic research studies; however, few studies have addressed parental psychological health effects associated with their child's participation in genomic studies, particularly when parents meet the threshold for clinical concern for depression. We aimed to determine if parents' depressive symptoms were associated with their child's participation in a randomized‐controlled trial of newborn exome sequencing. Parents completed the Edinburgh Postnatal Depression Scale (EPDS) at baseline, immediately post‐disclosure, and 3 months post‐disclosure. Mothers and fathers scoring at or above thresholds for clinical concern on the EPDS, 12 and 10, respectively, indicating possible Major Depressive Disorder with Peripartum Onset, were contacted by study staff for mental health screening. Parental concerns identified in follow‐up conversations were coded for themes. Forty‐five parents had EPDS scores above the clinical threshold at baseline, which decreased by an average of 2.9 points immediately post‐disclosure and another 1.1 points 3 months post‐disclosure (both p ≤.014). For 28 parents, EPDS scores were below the threshold for clinical concern at baseline, increased by an average of 4.7 points into the elevated range immediately post‐disclosure, and decreased by 3.8 points at 3 months post‐disclosure (both p <.001). Nine parents scored above thresholds only at 3 months post‐disclosure after increasing an average of 5.7 points from immediately post‐disclosure (p <.001). Of the 82 parents who scored above the threshold at any time point, 43 (52.4%) were reached and 30 (69.7%) of these 43 parents attributed their elevated scores to parenting stress, balancing work and family responsibilities, and/or child health concerns. Only three parents (7.0%) raised concerns about their participation in the trial, particularly their randomization to the control arm. Elevated scores on the EPDS were typically transient and parents attributed their symptomatology to life stressors in the postpartum period rather than participation in a trial of newborn exome sequencing. [ABSTRACT FROM AUTHOR]