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OBJECTIVES: The onset and severity of the clinical expression of most diseases that are of public health importance are influenced by genetic predisposition. The ability to assess human genetic predisposition for many diseases is increasing rapidly. Therefore, state public health agencies should be incorporating new developments in genetics and disease prevention into their core functions of assessment, policy development, and assurance. The authors assessed the status of this process. METHODS: The Council of State and Territorial Epidemiologists (CSTE) surveyed states about projects and concerns related to genetics and public health activities. Respondents were the Health Officer, the Maternal and Child Health/Genetics Program Director, the Chronic Disease Program Director, and the Laboratory Director. Where applicable, responses were categorized into assessment, policy development, and assurance functions. RESULTS: Thirty-eight (76%) state health departments responded. Ongoing genetics activities were assurance (82%), assessment (17%), and policy development (2%). In contrast, Health Officers responded that future genetics activities would be distributed differently: assurance, 41%; assessment, 36%; and policy development, 23%. Future assurance activities would be largely educational. Topics of interest and recently initiated activities in genetics were primarily assessment functions. Funding was the greatest concern, followed by lack of proven disease prevention measures and outcomes data. CONCLUSIONS: State health departments recognize a need to realign their activities to meet future developments in genetics. Lack of adequate resources, proven disease prevention measures, and outcomes data are potential barriers. Public health agencies need to develop a strategic plan to meet the opportunities associated with the development and implementation of genetic tests and procedures. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In this program a postpartum woman could consent to receive her newborn's human immunodeficiency virus test result from the New York State Newborn Screening Program. STUDY DESIGN: By state regulation each postpartum woman was counseled and offered her newborn's human immunodeficiency virus test result. With the mother's consent, newborn human immunodeficiency virus antibody test results from the Newborn Screening Program were sent to the baby's pediatrician; otherwise, test results were blinded. Data were analyzed for births from August 1, 1996, to January 31, 1997. RESULTS: Overall, 92.5% of women offered newborn human immunodeficiency virus testing consented to receive the result. Among 444 human immunodeficiency virus-positive women offered newborn testing, consented testing resulted in a 21.4% increase in knowledge of human immunodeficiency virus status from 72.3% (n = 321) at delivery to 93.7% (n = 416) after newborn testing; 6.3% (n = 28) of human immunodeficiency virus-positive women delivered of infants who did not consent apparently remained unaware of their human immunodeficiency virus status. CONCLUSION: Combined prenatal and consented newborn testing identified 94% of human immunodeficiency virus-positive mothers and exposed newborns, allowing early entry into care. Such testing may provide an opportunity for women not previously tested for the human immunodeficiency virus to learn their status but is not a substitute for universal prenatal human immunodeficiency virus counseling and consented human immunodeficiency virus testing. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) represents a wide range of neurodevelopmental disorders characterized by impairments in social interaction, language, communication and range of interests. Autism is usually diagnosed in children 3-5 years of age using behavioral characteristics; thus, diagnosis shortly after birth would be beneficial for early initiation of treatment., Aim: This retrospective study sought to identify newborns at risk for ASD utilizing bloodspot specimens in an immunoassay., Materials & Methods: The present study utilized stored frozen specimens from ASD children already diagnosed at 15-36 months of age. The newborn specimens and controls were analyzed by immunoassay in a multiplex system that included 90 serum biomarkers and subjected to statisical analysis., Results: Three sets of five biomarkers associated with ASD were found that differed from control groups. The 15 candidate biomarkers were then discussed regarding their association with ASD., Conclusion: This study determined that a statistically selected panel of 15 biomarkers successfully discriminated presumptive newborns at risk for ASD from those of nonaffected controls.

Biotinidase deficiency is an autosomal recessive syndrome caused by defects in the biotinidase gene, the product of which affects biotin metabolism. Newborn screening (NBS) for biotinidase deficiency can identify affected infants prior to onset of symptoms; biotin supplementation can resolve or prevent the clinical features. In NBS, dry blood spots (DBS) are usually tested for biotinidase enzyme activity by colorimetric analysis. By taking advantage of the multiplexing capabilities of the Luminex platform, we have developed a microsphere-based array genotyping method for the simultaneous detection of six disease causing mutations in the biotinidase gene, thereby permitting a second tier of molecular analysis. Genomic DNA was extracted from 3.2 mm DBS. Biotinidase gene sequences, containing the mutations of interest, were amplified by multiplexed polymerase chain reaction, followed by multiplexed allele-specific primer extension using universally tagged genotyping primers. The products were then hybridized to anti-tag carrying xTAG microspheres and detected on the Luminex platform. Genotypes were verified by sequencing. Genotyping results of 22 known biotinidase deficient samples by our xTAG biotinidase assay was in concordance with the results obtained from DNA sequencing, for all 6 mutations used in our panel. These results indicate that genotyping by an xTAG microsphere-based array is accurate, flexible, and can be adapted for high-throughput. Since NBS for biotinidase deficiency is by enzymatic assay, less than optimal quality of the DBS itself can compromise enzyme activity, while the DNA from these samples mostly remains unaffected. This assay warrants evaluation as a viable complement to the biotinidase semi-quantitative colorimetric assay.

Background: Severe combined immunodeficiency (SCID) fulfills many of the requirements for addition to a newborn screening panel. Two newborn screening SCID pilot studies are now underway using the T-cell receptor excision circle (TREC) assay, a molecular technique. Here we describe an immunoassay with CD3 as a marker for T cells and CD45 as a marker for total leukocytes that can be used with the Guthrie specimen., Methods: The multiplexing capabilities of the Luminex platform were used. Antibody pairs were used to capture and detect CD3 and CD45 from a single 3-mm punch of the Guthrie specimen. The assay for each biomarker was developed separately in identical buffers and then combined to create a multiplex assay., Results: Using calibrators made from known amounts of leukocytes, a detection limit of 0.25 x 10(6) cells/mL for CD3 and 0.125 x 10(6) cells/mL for CD45 was obtained. Affinity tests showed no cross-reactivity between the antibodies to CD3 and CD45. The multiplex assay was validated against 8 coded specimens of known clinical status and linked to results from the TREC assay that had identified them. All were correctly identified by the CD345 assay., Conclusions: The performance parameters of the CD345 assay met the performance characteristics generally accepted for immunoassays. Our assay classifications of positive specimens concur with previous TREC results. This CD345 assay warrants evaluation as a viable alternative or complement to the TREC assay as a primary screening tool for detecting T-cell immunodeficiencies, including SCID, in Guthrie specimens.

Background: Real-time quantitative PCR (qPCR) targeting a specific marker of functional T cells, the T-cell-receptor excision circle (TREC), detects the absence of functional T cells and has a demonstrated clinical validity for detecting severe combined immunodeficiency (SCID) in infants. There is need for a qPCR TREC assay with an internal control to monitor DNA quality and the relative cellular content of the particular dried blood spot punch sampled in each reaction. The utility of the qPCR TREC assay would also be far improved if more tests could be performed on the same newborn screening sample., Methods: We approached the multiplexing of qPCR for TREC by attenuating the reaction for the reference gene, with focus on maintaining tight quality assurance for reproducible slopes and for prevention of sample-to-sample cross contamination. Statewide newborn screening for SCID using the multiplexed assay was implemented, and quality-assurance data were recorded., Results: The multiplex qPCR TREC assay showed nearly 100% amplification efficiency for each of the TREC and reference sequences, clinical validity for multiple forms of SCID, and an analytic limit of detection consistent with prevention of contamination. The eluate and residual ghost from a 3.2-mm dried blood spot could be used as source material for multiplexed immunoassays and multiplexed DNA tests (Multiplex Plus), with no disruption to the multiplex TREC qPCR., Conclusions: Population-based SCID newborn screening programs should consider multiplexing for quality assurance purposes. Potential benefits of using Multiplex Plus include the ability to perform multianalyte profiling.

Primary congenital hypothyroidism (CH) is a common and preventable cause of intellectual disability. The incidence rate of CH has been reported to be increasing in the United States, but the factors behind the observed rate increase are not known. We summarize here the data presented at a workshop on CH, at which factors potentially related to the CH-incidence-rate increase (namely, race, ethnicity, sex, and birth outcomes) were evaluated. Data sources for the analyses included a national data set of newborn-screening results and state-specific data from newborn-screening programs in California, Massachusetts, New York, and Texas. The incidence rate of CH increased in the United States by 3% per year; however, an increase did not occur in all states, at a constant rate, or even at the same rate. Analysis of US data (1991-2000) showed a CH-incidence-rate increase only among white newborns. More recently, in California (2000-2007), the rate was constant in non-Hispanic newborns, but it increased among Hispanic newborns. In the national data, the CH-incidence rate increased similarly among boys and girls, whereas in Texas (1992-2006), the rate among boys increased significantly more than among girls and varied according to race and ethnicity. In Massachusetts (1995-2007), low birth weight newborns or newborns who had a delayed rise in thyrotropin concentration accounted for the majority of the recent rate increase. Race, ethnicity, sex, and pregnancy outcomes have affected the observed increasing incidence rate of CH, although there have been some inconsistencies and regional differences. The association with preterm birth or low birth weight could reflect the misclassification of some cases of transient hypothyroxinemia as true CH. Future studies of risk factors should focus on correct initial identification and reporting of demographic characteristics and pregnancy outcomes for cases of CH. In addition, long-term follow-up data of presumed cases of CH should be ascertained to differentiate true cases of CH from cases of transient hypothyroidism.

Background: Since its beginnings, newborn screening for cystic fibrosis (CF) using an assay for immunoreactive trypsinogen (IRT) has been plagued by a high rate of false-positive results (screen positive, diagnosis negative), despite attempts to reduce this rate by use of altered cutoffs and second-tier DNA testing. IRT exists as 2 isoforms: IRT1 and IRT2, with IRT2 being more closely aligned with pancreatic disease, including CF. Assay standardization between programs is a continuing problem because the IRT assays currently in use variously recognize either 1 or both isoforms. Here we report the development of a multiplexed assay for both forms of IRT simultaneously., Methods: Using 2 different Luminex bead sets, we developed assays for each IRT isoform separately and then combined them. Using the sum of IRT1 and IRT2 values (IRT1+IRT2), we compared the results with a CF kit currently in use., Results: In a sample set consisting of 16 cases confirmed positive for CF, we established a cutoff at >97 microg/L total IRT. Seven of 8 carriers with 1 CF mutation screen-positive by the standard method were also screen-positive by IRT1+IRT2. Of 32 cases screen-positive by standard IRT, 11 were screen-negative by IRT1+IRT2. None of these 11 cases had CF mutations identified by the screening program., Conclusions: These data indicate that the multiplex method with specificity for 2 isoforms of IRT has performance comparable to that of a standard IRT method and the advantage of improved standardization by detection of the 2 isoforms.

Patients with rare and complex diseases such as congenital adrenal hyperplasia (CAH) often receive fragmented and inadequate care unless efforts are coordinated among providers. Translating the concepts of the medical home and comprehensive health care for individuals with CAH offers many benefits for the affected individuals and their families. This manuscript represents the recommendations of a 1.5 day meeting held in September 2009 to discuss the ideal goals for comprehensive care centers for newborns, infants, children, adolescents, and adults with CAH. Participants included pediatric endocrinologists, internal medicine and reproductive endocrinologists, pediatric urologists, pediatric surgeons, psychologists, and pediatric endocrine nurse educators. One unique aspect of this meeting was the active participation of individuals personally affected by CAH as patients or parents of patients. Representatives of Health Research and Services Administration (HRSA), New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), and National Newborn Screening and Genetics Resource Center (NNSGRC) also participated. Thus, this document should serve as a "roadmap" for the development phases of comprehensive care centers (CCC) for individuals and families affected by CAH.

Congenital hypothyroidism and congenital adrenal hyperplasia are included in many newborn screening (NBS) panels worldwide and in all state-sponsored programs in the United States. Both conditions meet the fundamental prerequisites for NBS: high incidence in the population; biomarkers in the dried blood specimen that are easily detected; and, effective therapies to lessen, if not prevent, the sequelae of late or no treatment. In this review, the history of NBS is discussed for these 2 conditions. The technologies and protocols used in their detection, and related subjects such as genetics, and treatment and outcomes, are also discussed.

Patients identified in newborn screening programs can be among the most vulnerable during a disaster due to their need to have prompt diagnosis and medical management. Recent disasters have challenged the ability of newborn screening programs to maintain the needed continuity during emergency situations. This has significant implications for the newborn screening laboratories, the diagnostic confirmation providers, and the patients who either require diagnosis or maintenance of their therapeutic interventions. In 2007, the National Coordinating Center (NCC) for the Regional Genetics and Newborn Screening Collaboratives (RCs) sponsored a meeting involving representatives of the Regional Genetics and Newborn Screening Collaborative Groups, state newborn screening programs, providers of diagnosis and confirmation services, manufacturers of equipment, medical foods, and other treatments used in patients identified in newborn screening programs, and individuals from agencies involved in disaster response including the National Disaster Medical Service, the Centers for Disease Control and Prevention, the Emergency Management Assistance Compact, the Federal Emergency Management Agency, and others. In addition to developing contingency plans for newborn screening, we have considered other uses of genetics as it is used in DNA-based kinship identification of mass casualties. The meeting resulted in the description of a wide range of issues facing newborn screening programs, provider groups, and patients for which emergency preparedness development is needed in order that appropriate response is enabled.

Purpose: This study explored the feasibility of statewide reporting of cystic fibrosis fetal diagnostic testing results to the newborn screening program through the birth hospital., Methods: We evaluated trends in offering and documenting cystic fibrosis carrier screening among prenatal care providers through a survey of 100 medical records of patients who gave birth at St. Vincent's Hospital Manhattan. The hospital's protocol for reporting human immunodeficiency virus testing history to the state program was delineated and adapted in developing an algorithm for cystic fibrosis. Feedback from hospital staff with regard to data transcription and the prospect of transferring cystic fibrosis prenatal information was obtained., Results: Of 98 patients who had prenatal records made available to the birth hospital, 62% had cystic fibrosis carrier screening, 14% declined screening, and 24% had no documentation of their screening history. The hospital staff viewed the transcription of information as relatively simple; however, missing information is a common occurrence that delays the process and results in incomplete data transfer., Conclusions: Perinatal transfer of cystic fibrosis prenatal information modeled on the system used for reporting human immunodeficiency virus testing history is feasible. However, it will require standardized reporting of cystic fibrosis screening and testing history on the mother's prenatal records among prenatal care providers.

Temporal biomonitoring studies can assess changes in population exposures to contaminants, but collection of biological specimens with adequate representation and sufficient temporal resolution can be resource-intensive. Newborn Screening Programs (NSPs) collect blood as dried spots on filter paper from nearly all infants born in the United States (U.S.). In this study, we investigated the use of NSP blood spots for temporal biomonitoring by analyzing perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in 110 New York State (NYS) NSP blood spot composite specimens collected between 1997 and 2007, representing a total of 2640 infants. All analytes were detected in > or =90% of the specimens. Concentrations of PFOS, PFOSA, PFHxS, and PFOA exhibited significant exponential declines after the year 2000, coinciding with the phase-out in PFOS production in the U.S. Calculated disappearance half-lives for PFOS, PFHxS, and PFOA (4.4, 8.2, and 4.1 years, respectively) were similar to biological half-lives reported for retired fluorochemical workers. Our results suggest sharp decreases in perinatal exposure of NYS infants to PFOS, PFOSA, PFHxS, and PFOA and demonstrate, for the first time, the utility of NSP blood spots for assessment of temporal trends in exposure.

Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is one of the most common fatty acid oxidation disorders. A subpopulation of children with MCADD present with metabolic crisis induced by fasting or illness, become lethargic, and can experience seizures or coma, culminating in a 20% mortality rate during the first episode. The frequency of these metabolic crises can be reduced with early diagnosis and treatment. The prevalence of MCADD in the United States is estimated to be 1 per 15,000 with p.K304E (c.985A > G) accounting for 90% of mutant alleles. In an 18-month period after initiating screening, the New York State Newborn Screening Mass Spectrometry Laboratory screened 385,893 newborns and referred 511 samples with elevated (>or=0.3 micromol/L) octanoylcarnitine (C8) levels for molecular testing. Of these referrals, six p.K304E homozygotes and 154 heterozygotes were identified. Twenty infants were biochemically confirmed with MCADD, per report from the child's pediatrician and/or treatment center. In these 20 cases, p.K304E accounted for only 47.5% of the mutant alleles. Further testing showed a second variant, p.Y42H, accounted for 7.5% of mutant alleles while the remaining 45% were unknown. Samples from all diagnosed non-p.K304E homozygous infants, and samples with C8 levels >or=1.0 micromol/L were sequenced (n = 16). Six novel and seven previously reported mutations were detected. These results suggest that p.K304E has a far lower representation in New York newborns with MCADD than current literature estimates and its full mutational spectrum is still unknown., ((c) 2008 Wiley-Liss, Inc.)

Mandated screening of newborns for congenital hypothyroidism (CH) in NYS was initiated in l978. Currently, every newborn screening program in the U.S. includes CH in its panel. Between 1978 and 2005, 7.4 million newborns were screened for CH in NYS. In NYS, between 1978 and 2005, the incidence of CH has increased by 138%. Nationwide (excluding NYS data), with nearly 58 million infants screened between 1987 and 2002, the incidence has increased 73% between 1987 and 2002. These data and possible reasons for the increases are discussed, though no definitive causes are identified.

Several systemic and cellular markers of 3'-azido-3'-dideoxythymidine (AZT) metabolism and AZT incorporation into nuclear DNA were measured in cord blood from uninfected infants born to HIV-1-infected mothers receiving prepartum therapies based on AZT or AZT in combination with 2',3'-dideoxy-3'-thiacytidine (3TC). In addition, the relationships among these pharmacological end points, levels of AZT-DNA incorporation, and the previously reported mutagenic responses in these infants were evaluated. AZT- and 3TC-specific radioimmunoassays (RIAs), or HPLC coupled with AZT-RIA, were used to measure plasma levels of AZT and the AZT-glucuronide, and cellular levels of AZT, phosphorylated AZT, and DNA incorporation of AZT or 3TC in cord blood mononuclear cells from treated infants compared with unexposed controls born to HIV-uninfected mothers. Fewer infants had detectable AZT-DNA incorporation levels in the group exposed to AZT (71%; n = 7) compared with those receiving AZT-3TC (100%; n = 21), and the mean AZT-DNA incorporation for AZT-exposed infants (14.6 +/- 6.3 AZT/10(6) nucleotides) was significantly lower than that in AZT-3TC exposed infants (51.6 +/- 10.2 AZT/10(6) nucleotides; P = 0.028). Low levels of 3TC-DNA incorporation found in a few AZT-3TC-exposed newborns correlated with AZT-DNA incorporation values in the same samples. Among the metabolites studied, there were positive correlations between levels of AZT-diphosphate and AZT-triphosphate, and AZT-triphosphate and AZT-DNA incorporation, in nucleoside analog-exposed infants. Levels of AZT-DNA incorporation, however, did not correlate well with the reported frequencies of somatic mutations in the same population of nucleoside analog-treated children. While these data support the continued use of AZT-based therapies during pregnancy, infants receiving prepartum AZT should be monitored long-term for adverse health effects., ((c) 2006 Wiley-Liss, Inc.)

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.

Purpose: A population-based cohort from three state newborn screening programs was used to describe beta-globin gene cluster variation., Methods: Blood spots from newborns homozygous for HbS were genotyped for five restriction fragment length polymorphisms (RFLPs) to construct beta-globin haplotypes. Haplotype distributions were compared by race/ethnicity and sex. Expected heterozygosities were calculated and compared with observed heterozygosities., Results: Haplotype distributions did not differ between sexes for either blacks or Hispanics. Neither racial/ethnic group deviated from Hardy-Weinberg equilibrium; however, Hispanics had higher heterozygosity at two RFLPs compared with blacks., Conclusion: The differences between populations probably reflect recent migration and admixture rather than selection.

Docosahexaenoic acid, found lacking in animal models of cystic fibrosis, has been proposed as a dietary supplement therapy for this genetic disorder. Alpha-fetoprotein, which binds and transports docosahexaenoic acid, may be a useful marker to improve the management and follow-up in newborn screening programs for cystic fibrosis, because only 20% of such infants are diagnosed at birth.

The frequency of Wilson's disease in many populations is thought to be about one in 40000 persons, based on case and autopsy studies. Although the Wilson's disease gene has been identified, there is such a large number of mutations already known that it is not currently feasible to determine disease gene frequency by mutation analysis of a population. We have used a novel approach to obtain an estimate of the number of cases of Wilson's disease expected at birth in the US Caucasian population. We used data from four studies to determine that approximately one-third of Wilson's disease mutations in US Caucasian Wilson's disease patients are due to His-->Gln at the 1069 position. We then determined the frequency of this mutation in random DNA samples from 2601 US Caucasian newborns to be 0.285%. Multiplying by three gives an expected Wilson's disease heterozygote frequency of 0.855% and an allele frequency of 0.428%, or 0.00428. These data translate into a Wilson's disease frequency of about one in 55000 births. The 95% confidence interval is rather broad, ranging from about one in 18000 to one in 700000 births, but will be reduced as more data are added.

We developed a fluorescent immunoassay to simultaneously measure antibodies to three HIV-1 antigens from newborn dried blood-spot specimens. The multiplexed assay uses fluorescent microspheres and a flow analyzer. The procedure is sensitive, precise and accurate, and can be expanded to simultaneously measure additional multiple analytes from a single specimen.

We surveyed clinical genetics centers to assess current cystic fibrosis (CF) screening practices with regard to clinical and laboratory aspects. The survey was developed by the CF committee of the Genetics Network of the Empire State, Puerto Rico, and the U.S. Virgin Islands (GENES) to gauge changes in trends following the April, 1997, NIH Consensus Statement recommending the offering of CF carrier screening to all pregnant patients. Thirty-five of 45 Centers (78%) returned the survey, which was mailed in June, 1998. Sixteen centers currently offer population-based screening, whereas 19 centers do not. Reasons cited for not offering testing included the low risk for CF in ethnic groups served, lack of data about test sensitivity in the populations served, and the absence of CF screening policies in the current standards of care. Approximately half (56%) of genetics centers that are offering testing altered their screening policy following the NIH Consensus statement, either by offering screening to patients of higher-risk ethnicities or by offering it to all patients. Less than half of the Centers that offer routine carrier screening offer screening to all patients regardless of ethnicity. This report is an initial step in documenting and understanding the current service practices regarding CF carrier testing in a diverse region. Our conclusions: (1) Screening practices vary widely among genetic centers in the region. (2) The decision to offer routine CF carrier screening is largely based on ethnicity of the patient population served. (3) Methods used to screen pregnant women and their partners in this part of the country reflect the diversity of models employed throughout the United States. (4) CF screening practices in the GENES region have changed significantly following the April, 1997, NIH consensus statement.

Ion-exchange HPLC was developed for testing dried blood-spot specimens from newborns. The method is suitable for quantitative confirmatory testing of abnormal specimens detected in the New York State Newborn Screening Program. Positive specimens were initially identified among all New York State newborns with semiquantitative bacterial inhibition assays (BIA) for aminoacidopathies, including phenylketonuria (PKU) and non-PKU hyperphenylalaninemia (HP), maple syrup urine disease, and homocystinuria. A selection of 1346 specimens from routine BIA screening, including 131 newborns with PKU or persistent HP, were tested by HPLC. Of 179 BIA results that were falsely positive, 98 (55%) were also falsely positive by HPLC in which the Phe/Tyr ratio was the discriminator and the threshold was set to attain 100% sensitivity. Investigation of three multivariate discriminatory methods revealed that linear discriminant analysis excluded all but 35 (20%) of the BIA false-positives.

Guthrie cards derived from the New York State Newborn Screening Program were utilized to develop a rapid, economical method for amplifying multiple genes to detect mutations that impact public health. These specimens are untraceable to the donor because identifiers are removed and discarded; therefore, these pilot studies were carried out anonymously. The sample preparation requires minimal manipulation, is amenable to automation, and is useful in laboratories which routinely process large numbers of samples, such as those in typical newborn screening laboratories. Multiple gene fragments may be amplified from a 1 mm punch which contains less than 1 microl of whole blood. The blood spots used in these studies contain sufficient material for up to 25 amplification reactions which multiplex at least four different gene fragments each. Since sufficient material remains on the card after the routine testing is complete, this simple assay can greatly expand the efficacy of current newborn screening programs by permitting DNA diagnosis of some disorders when indicated, particularly those in which genotype-phenotype correlations are useful. In addition to newborn screening specimens, this method is also applicable to whole blood from adults after phlebotomy and from lymphoblastoid cell lines. Use of filter paper for DNA analysis is particularly useful for shipped specimens or for population studies whose subjects are refractory to phlebotomy.

A collaborative March of Dimes study was designed to examine the utility of dried blood spot (DBS) materials routinely collected from newborns as a source for monitoring cocaine exposure and to assess the prevalence of cocaine use among childbearing women in Georgia. We used a modified urinary radioimmunoassay (RIA) to anonymously detect the cocaine metabolite benzoylecgonine (BE) in DBSs. Extensive efforts were undertaken to assure absolute nonlinkage of BE data to any individual. The positive results found by RIA were confirmed by a mass spectrometry (MS) method specifically developed to detect BE in DBSs. BE was measured in 23,141 DBSs collected during 2 months of routine newborn screening in Georgia. A good correlation was observed for RIA results versus MS results (r2 = 0.97). The estimated minimal statewide BE prevalence was 4.8 per 1000 childbearing women. We demonstrated that immunoassay testing for cocaine without confirmatory testing can yield falsely elevated prevalence rates. When proper confirmatory testing is done, DBSs are a valuable source for population-based monitoring of substance abuse among childbearing women.

Alpha thalassemia trait (alpha-thal-1) is a common cause of microcytosis in black and Asian populations. A small amount of hemoglobin Barts (2-8%) is transiently present in affected infants at birth and detectable in many newborn screening laboratories; it is a fast-moving hemoglobin on electrophoresis. In order to determine whether a report of a "fast hemoglobin variant" on newborn hemoglobinopathy screening is associated with a diagnosis of alpha thalassemia trait, hemoglobin concentration, red blood cell indices, and peripheral blood smear examination were performed on 18 infants referred for hematologic evaluation of a "fast hemoglobin variant" on newborn screening. All 18 infants with this diagnosis referred for consultation were black; ages ranged from 24 to 86 days (median 40 days). Six of 18 infants (33%) were mildly anemic for age and all 18 were microcytic. The prevalence of a "fast variant" among infants born at our institution is 2.5%. In that conditions other than alpha-thal-1 that cause microcytosis in early infancy are very uncommon, we conclude that all 18 of our infants with a fast hemoglobin on newborn screening likely have alpha-thal-1. The newborn screening result is thus a commonly and readily available laboratory report that specifically supports a diagnosis of alpha-thal-1, a diagnosis with significant clinical and genetic implications that is usually made only by exclusion.

The present study evaluated the utility of a portable metabolic measurement system, the Aerosport TEEM 100. A total of 505 data points [242 from incremental (INC) and 263 from constant load (CL) exercise] were collected on 12 subjects (age = 25 +/- 4 yr), by placing the Aerosport TEEM 100 medium flow pneumotach and mouthpiece in-line with a validated system, the Rayfield system. When VO2 values were separated into categories (< 1.5, 1.5-2.0, 2.0-2.5, 2.5-3.0, > 3.0 l.min-1), there was a small but statistically significant difference between the two metabolic measurement systems for VO2, VCO2, VE, RER, %ECO2, and %EO2 during both INC and CL exercise and measurement error for VO2 ranged between 2% and 11%. Correlations for VO2 values during INC and CL exercise between the two systems were r = 0.95 (SEest +/- 0.18 l.min-1) and r = 0.96 (SEest +/- 0.29 l.min-1), respectively. Correlations for RER were r = 0.82 (SEest +/- 0.08) and r = 0.47 (SEest +/- 0.11), for INC and CL, respectively. Results from the present investigation indicate that the Aerosport TEEM 100 has utility for the assessment of VO2, but the estimation of carbohydrate and fat utilization from RER should be used with caution.

These guidelines provide scientific information for policy development by state health departments considering appropriate use of newborn screening specimens after screening tests are finished. Information was collected, debated, and formulated into a policy statement by the Newborn Screening Committee of the Council of Regional Networks for Genetic Services (CORN), a federally funded national consortium of representatives from 10 regional genetics networks. Newborn screening programs vary widely in approaches and policies concerning residual dried blood spot samples (DBS) collected for newborn screening. Recognition of the epidemiological utility of DBS samples for HIV seroprevalence surveys and a growing interest in DBSs for DNA analysis has intensified consideration of issues regarding retention, storage, and use of residual DBS samples. Potentially these samples provide a genetic material "bank" for all newborns nationwide. Their values as a resource for other uses has already been recognized by scientists, administrators, and judicial officials. Programs should promulgate rules for retention and use of residual newborn screening DBS samples based on scientifically valid information. Banking of newborn samples as sources of genetic material should be considered in light of potential benefit or harm to society.

Implicit in the New York State Newborn HIV Seroprevalence Study is the assumption that newborns of all New York State residents are tested for human immunodeficiency virus (HIV) antibodies. We examined this assumption by describing that part of the 1988 New York newborn population not tested in the HIV seroprevalence study and assessing any bias contributed by this group. Of the expected total HIV specimens 1.5 percent were never received by the Newborn Screening Program, 0.5 percent were invalid specimens for which no repeat specimen could be obtained, and 1.7 percent were unsuitable or of insufficient quantity to be tested for HIV antibody. Thus 96.3 percent of all 1988 New York newborns were tested for HIV antibody. Black infants from New York City and low-birthweight infants were represented disproportionately among those not tested. Assignment of all untested newborn to HIV-positive status increased the seroprevalence rate 17 percent (0.64 percent to 0.75 percent).

Several neurally excitant amino acids were injected into the third ventricle of anesthetized male rats, and plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured. LH levels increased following injections of 2.0 mum glutamate, lysine, or beta-alanine. Glycine (2.0 mum), alpha-alanine (2.0 mum), and 0.9% saline were ineffective in altering LH levels. None of the amino acids tested significantly altered FSH levels. Of the 3 amino acids which raised blood LH levels following an intraventricular injection, i.e., glutamate, beta-alanine, and lysine, only lysine caused a significant increase in LH levels following injection into the pituitary. The present study provides evidence for a possible role for certain neurally excitant amino acids in the neuronal control of LH secretion.