Nancy S. Green

Increased Risk of Adverse Neurological Development for Late Preterm Infants

OBJECTIVE To assess the risks of moderate prematurity for cerebral palsy (CP), developmental delay/mental retardation (DD/MR), and seizure disorders in early childhood. STUDY DESIGN Retrospective cohort study using hospitalization and outpatient databases from the Northern California Kaiser Permanente Medical Care Program. Data covered 141 321 children > or =30 weeks born between Jan 1, 2000, and June 30, 2004, with follow-up through June 30, 2005. Presence of CP, DD/MR, and seizures was based on International Classification of Diseases, Ninth Revision codes identified in the encounter data. Separate Cox proportional hazard models were used for each of the outcomes, with crude and adjusted hazard ratios calculated for each gestational age group. RESULTS Decreasing gestational age was associated with increased incidence of CP and DD/MR, even for those born at 34 to 36 weeks gestation. Children born late preterm were >3 times as likely (hazard ratio, 3.39; 95% CI, 2.54-4.52) as children born at term to be diagnosed with CP. A modest association with DD/MR was found for children born at 34 to 36 weeks (hazard ratio, 1.25; 95% CI, 1.01-1.54), but not for children in whom seizures were diagnosed. CONCLUSIONS Prematurity is associated with long-term neurodevelopmental consequences, with risks increasing as gestation decreases, even in infants born at 34 to 36 weeks.

Estimated effect of 17 alpha-hydroxyprogesterone caproate on preterm birth in the United States

OBJECTIVE: A multicenter, randomized placebo-controlled trial among women with singleton pregnancies and a history of spontaneous preterm birth found that weekly injections of 17 alpha-hydroxyprogesterone caproate (17P), initiated between 16 and 20 weeks of gestation, reduced preterm birth by 33%. The current study estimated both preterm birth recurrence and the potential reduction in the national preterm birth rate. METHODS: Using 2002 national birth certificate data, augmented by vital statistics from 2 states, we estimated the number of singleton births delivered to women eligible for 17P through both a history of spontaneous preterm birth and prenatal care onset within the first 4 months of pregnancy. The number and rate of recurrent spontaneous preterm births were estimated. To predict effect, the reported 33% reduction in spontaneous preterm birth attributed to 17P therapy was applied to these estimates. RESULTS: In 2002, approximately 30,000 recurrent preterm births occurred to women eligible for 17P, having had a recurrent preterm birth rate of 22.5%. If 17P therapy were delivered to these women, nearly 10,000 spontaneous preterm births would have been prevented, thereby reducing the overall United States preterm birth rate by approximately 2%, from 12.1% to 11.8% (P < .001), with higher reductions in targeted groups of eligible pregnant women. CONCLUSION: Use of 17P could reduce preterm birth among eligible women, but would likely have a modest effect on the national preterm birth rate. Additional research is urgently needed to identify other populations who might benefit from 17P, evaluate new methods for early detection of women at risk, and develop additional prevention strategies. LEVEL OF EVIDENCE: III

Attitudes about genetics in underserved, culturally diverse populations.

Objective: New medical discoveries regarding genetic susceptibility to common chronic diseases, and the decoding of the human genome have increased public attention to genetics. What information is understood and what attitudes exist towards genetics and genetic research have not been well examined in underserved, culturally diverse communities. Methods: To better understand attitudes and beliefs towards genetics and genetic testing in these groups, we conducted eight focus groups with 55 patients and health care workers in New York City and Westchester, N.Y., in English, Spanish, and Chinese. Results: Focus group participants had limited understanding about genetics or genetic testing. Newborn screening was the least-known genetic issue, even among health care workers. Regardless of their cultural group, most participants expressed a desire for more information about genetics and genetic tests. Latinos and Chinese participants generally expressed positive attitudes towards genetic studies and genetic testing, with the possibility of preventing diseases cited as the main advantage. Black Americans and Non-Hispanic Whites reported mixed feelings about genetic research and genetic testing. Concerns expressed included: anxiety before receiving test results or waiting for a disease to develop, fear of genetic discrimination by health and life insurance companies and employers, not having the financial means to deal with genetic diseases in themselves or a sick child, concern that children and adults are having too many tests. Black Americans expressed the most concern for possibly harmful use of genetic information. Conclusions: Minority populations of diverse cultures have limited knowledge about genetics and genetic testing, would like to have more information, and are not well reached by the current educational approaches. Participants knew the least about newborn screening, a test that is mandatory in the New York State. While genetic knowledge by minority populations was perhaps not different from the level of knowledge of consumers in general, minority populations are at particular risk of being left behind because of historically poor access to information and services.

Systematic Evidence Review of Newborn Screening and Treatment of Severe Combined Immunodeficiency

CONTEXT: Severe combined immunodeficiency (SCID) is a group of disorders that leads to early childhood death as a result of severe infections. Recent research has addressed potential newborn screening for SCID. OBJECTIVE: To conduct a systematic review of the evidence for newborn screening for SCID, including test characteristics, treatment efficacy, and cost-effectiveness. METHODS: We searched Medline and the OVID In-Process & Other Non-Indexed Citations databases. We excluded articles if they were reviews, editorials or other opinion pieces, or case series of fewer than 4 patients or if they contained only adult subjects or nonhuman data. The remaining articles were systematically evaluated, and data were abstracted by 2 independent reviewers using standardized tools. For topics that lacked published evidence, we interviewed experts in the field. RESULTS: The initial search resulted in 719 articles. Twenty-six met inclusion criteria. The results of several small studies suggested that screening for SCID is possible. Interviews revealed that 2 states have begun pilot screening programs. Evidence from large case series indicates that children receiving early stem-cell transplant for SCID have improved outcomes compared with children who were treated later. There is some inconclusive evidence regarding the need for donor-recipient matching and use of pretransplant chemotherapy. Few data on the cost-effectiveness of a SCID-screening program. CONCLUSIONS: Evidence indicates the benefits of early treatment of SCID and the possibility of population-based newborn screening. Better information on optimal treatment and the costs of treatment and screening would benefit policy makers deciding among competing health care priorities.

Neonatal screening by DNA microarray: spots and chips.

Newborn screening (NBS) is a public-health genetic screening programme aimed at early detection and treatment of pre-symptomatic children affected by specific disorders. It currently involves protein-based assays and PCR to confirm abnormal results. We propose that DNA microarray technology might be an improvement over protein assays in the first stage of NBS. This approach has important advantages, such as multiplex analysis, but also has disadvantages, which include a high initial cost and the analysis/storage of large data sets. Determining the optimal technology for NBS will require that technical, public health and ethical considerations are made for the collection and extent of analysis of paediatric genomic data, for privacy and for parental consent.

Committee report: Method for evaluating conditions nominated for population-based screening of newborns and children.

Abstract: The Secretarys Advisory Committee on Heritable Disorders in Newborns and Children is charged with evaluating conditions nominated for addition to the uniform screening panel and consequently making recommendations to the secretary of the US Department of Health and Human Services. This report describes the framework by which the committee approaches its task. Key decision nodes include initial review of every nomination to determine whether conditions are amenable for systematic evidence review, review of systematic evidence reviews conducted by the committees external review group, and deliberation and formal recommendation for addition or exclusion to the uniform panel. Data analyzed include the accuracy and specificity of screening and diagnostic tests for nominated disorders, the extent of predicted health benefits, harms impact on disease course, and cost from early diagnosis and treatment. The committee process is guided by approaches used by similar entities, but more flexible criteria are sometimes needed to accommodate data limitations stemming from the rarity of many of these conditions. Possible outcomes of committee review range from recommendation to add a nominated condition to the uniform panel; provide feedback on specific gaps in evidence that must be addressed before making a decision; or rejection of a nomination (e.g., because of identified harms). The committees structured evidence-based assessment of nominated conditions supports a consistently rigorous, iterative and transparent approach to its making recommendations regarding broad population-based screening programs for rare conditions in infants and children.

Weighing the evidence for newborn screening for early-infantile Krabbe disease

Purpose: To summarize the evidence regarding screening, diagnosis, and treatment of early-infantile Krabbe disease in consideration of its addition to the core panel for newborn screening as has been done in New York state.Methods: Systematic review of articles indexed in MEDLINE and Embase published between January 1988 and July 2009. Thirteen articles describing studies related to screening, diagnosis, or treatment were included in this review.Results: Case series studies suggest that allogeneic hematopoietic stem-cell transplantation soon after the development of signs or symptoms of early-infantile Krabbe disease decreases early-childhood mortality and may improve neurodevelopment. However, limited data suggest there may be loss of motor function among some children who undergo transplantation. No long-term follow-up data are available from these case series. Of the ∼550,000 newborns reported to have been screened in New York, 25 tested positive. None of these were clinically recognized to have Krabbe disease prior these results. Four were considered to be high risk for early-onset Krabbe disease. Two were subsequently diagnosed and underwent stem-cell transplantation, of whom one died from complications. No data are available regarding the impact on families of a positive newborn screen.Conclusions: Although early treatment with hematopoietic stem-cell transplant seems to alter early-childhood mortality and some of the morbidity associated with early-infantile Krabbe disease, significant gaps in knowledge exist regarding the accuracy of screening, the strategy for establishing diagnosis, the affect of a positive screen on families, the benefits and harms of treatment, and long-term prognosis.

Decision-making process for conditions nominated to the Recommended Uniform Screening Panel: statement of the US Department of Health and Human Services Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children

Purpose:The US Secretary of Health and Human Services provides guidance to state newborn screening programs about which conditions should be included in screening (i.e., the “Recommended Uniform Screening Panel”). This guidance is informed by evidence-based recommendations from the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children. This report describes the Advisory Committee’s revised decision-making process for considering conditions nominated to the panel.Methods:An expert panel meeting was held in April 2012 to revise the decision matrix, which helps to guide the recommendation process. In January 2013, the Advisory Committee voted to adopt the revised decision matrix.Results:The revised decision matrix clarifies the approach to rating magnitude and certainty of the net benefit of screening to the population of screened newborns for nominated conditions, and now includes the consideration of the capability of state newborn screening programs for population-wide implementation by evaluating the feasibility and readiness of states to adopt screening for nominated conditions.Conclusion:The revised decision matrix will bring increased quality, transparency, and consistency to the process of modifying the recommended uniform screening panel and will now allow formal evaluation of the challenges that state newborn screening programs face in adopting screening for new conditions.Genet Med 16 2, 183–187.

Parental and other factors associated with hydroxyurea use for pediatric sickle cell disease

Hydroxyurea (HU) is highly effective treatment for sickle cell disease (SCD). While pediatric use of HU is accepted clinical practice, barriers to use may impede its potential benefit.

Public perceptions about prematurity: a national survey☆

BACKGROUND More than 460,000 preterm babies are born annually in the United States, with rates varying depending on the mothers race/ethnicity. Preliminary evidence suggests that the general public may have a lack of knowledge and misconceptions about preterm birth. METHODS A national telephone survey of U.S. adults, over-sampling for black and Hispanic women, was conducted in 2002 to assess peoples knowledge, attitudes, and beliefs related to preterm birth (N=1967). Analyses included racial/ethnic differences among womens responses and comparisons to mens responses. RESULTS Prematurity was named by <1% of women as the most important issue facing pregnant women and infants. Overall, 34% of women and 31% of men felt that prematurity is a common problem in the United States, and 38% of women and 25% of men believed prematurity to be a serious problem in the United States. More black and Hispanic women considered prematurity to be common and serious. A majority of women (65%) and men (59%) attributed preterm births to risky prenatal maternal behaviors. CONCLUSIONS Although nearly one in eight babies is born prematurely, most U.S. adults do not consider prematurity to be a serious public health problem. While the etiology can be identified in only half of spontaneous preterm births, the public largely blames the mothers prenatal behavior. Misperceptions are prevalent and may impede future research and prevention efforts if not corrected.