Survey of pediatrician practices in retrieving statewide authorized newborn screening results.

OBJECTIVE: Mandated state newborn screening programs for the approximately 4 million infants born each year in the United States involves the following 5 components: 1) initial screening, 2) immediate follow-up testing of the screen-positive newborn, 3) diagnosis confirmation (true positive versus false positive), 4) immediate and long-term care, and 5) evaluation of all of the components of the system, including process and outcomes measures. Smooth functioning of this system requires pretest education of the parents as well as education and involvement of all health care providers who interact with the newborn screening system. Although extensive literature is available concerning public health aspects, technical standards/protocols, and discussion of the interfaces among the 5 components of the system, little information is available regarding physician awareness, involvement, and interactions with the system. The objective of this study was to determine, through a survey, primary care pediatricians' satisfaction with their state's newborn screening program. This was reflected in survey questions that asked how pediatricians were notified of the results of newborn screening tests that were performed on infants in their practice. METHODS: Two thousand questionnaires were sent to primary care pediatricians in all 50 states and the District of Columbia regarding their practices in retrieving statewide newborn screening results. Of the 2000 surveys, 574 (29%) responses from primary care pediatricians who care for at least 1 to 5 newborns each week form the basis of this report. Also reported are the commentaries of the physicians concerning their specific practices, overall assessment of the system, and ideas for improvement. RESULTS: Physicians reported their general satisfaction with the newborn screening system's ability to retrieve screen-positive infants for follow-up testing. However, communication and partnership with the primary care pediatrician regarding accessibility and timely retrieval of newborn screening test results was deemed less than optimal. Thirty-one percent of respondents indicated that notification for screen-positive test results was greater than 10 days, whereas 26% indicated that they do not receive the results of screen-negative tests and need to develop office procedures (contact birth hospital or state laboratory) to obtain results. Twenty-eight percent indicated that they do not actively seek results of newborn screening for their patients and presume that "no news is good news." Barriers to retrieving test results included that infants were born at hospitals where the physician does not have privileges, there were new transfers to the practice, infants were born in other states, personnel time was needed to track results, and there was a lack of a cohesive communication/reporting system that includes the primary care physician as an integral partner in the newborn screening communication process. Ninety-two percent of physicians would welcome an enhanced state system with direct communication to the primary care pediatrician as well as the birth hospital. CONCLUSION: Pediatricians recognize and endorse the benefits of newborn screening and believe that they play an important role in the efficient functioning of the system. An enhanced physician partnership with the newborn screening program will enable the timely follow-up of the screen-positive newborn for confirmatory testing. All test results need to be communicated to the pediatrician in a timely and efficient manner: 7 days for screen-positive results and 10 to 14 days for all results. Newborn screening test results of new patients who enter the practice should be available at the time of the first well-infant visit, ideally by 2 weeks of age. The majority of primary care pediatricians acknowledge the need to establish office protocols for the retrieval of newborn screening test results and would welcome an enhanced direct communication system with the state newborn screening program.

Interstitial insertion of Y-specific DNA sequences including SRY into chromosome 4 in a 45,X male child.

A 45,X chromosome complement was found in the lymphocytes and skin fibroblast cultures of a male infant with minor facial anomalies and gastrointestinal abnormalities. Fluorescence in situ hybridization (FISH) studies with DNA probes specific for the entire Y chromosome (painting) and SRY identified insertion of a short piece of Y chromosome DNA, including the SRY region, into a der(4) chromosome at 4p15. FISH studies with DNA probes specific for Wolf-Hirschhorn syndrome (WHS) and telomere of 4p indicated that these 2 regions were intact and that the insertion of Y DNA had occurred proximal to the WHS region. High-resolution chromosome analysis performed after FISH studies showed an altered banding pattern of 4p at the region of insertion. The typical Giemsa dark band of 4p15 was consistently replaced by a gray band; this probably indicates deletion of the distal part of 4p15. The consequences of the double-chromosome anomaly in this patient were discussed in relation to his phenotype.

Congenital diaphragmatic hernia and ipsilateral limb reduction defect: a new case, long-term follow-up and review of the literature.

There have been a small number of documented cases of isolated congenital diaphragmatic hernia and ipsilateral limb defects. Early cervical neural crest injury has been postulated as the mechanism behind the coexistence of these two defects. We present a case of left-sided congenital diaphragmatic hernia and ipsilateral radial ray defect consisting of thumb hypoplasia and absent radius. Our patient is an adult who presented for reproductive counselling providing an opportunity for long-term follow-up.

Familial transmission of a deletion of chromosome 21 derived from a translocation between chromosome 21 and an inverted chromosome 22.

Chromosome analysis of a newborn boy with Down syndrome resulted in the identification of a family with an unusual derivative chromosome 22. The child has 46 chromosomes, including two chromosomes 21, one normal chromosome 22, and a derivative chromosome 22. Giemsa banding and fluorescent in situ hybridization (FISH) studies show that the derivative chromosome is chromosome 22 with evidence of both paracentric and pericentric inversions, joined to the long arm of chromosome 21 from 21q21.2 to qter. The rearrangement results in partial trisomy 21 extending from 21q21.2 to 21q terminus in the patient. The child's mother, brother, maternal aunt, and maternal grandmother are all carriers of the derivative chromosome. All have 45 chromosomes, with one normal chromosome 21, one normal chromosome 22, and the derivative chromosome 22. The rearrangement results in the absence of the short arm, the centromere, and the proximal long arm of chromosome 21 (del 21pter-21q21.2) in carriers. Carriers of the derivative chromosome in this family have normal physical appearance, mild learning disabilities and poor social adjustment.

Six patients with oral-facial-digital syndrome IV: the case for heterogeneity.

The oral-facial-digital syndromes (OFDS) have in common minor facial and oral anomalies (including tongue lobulation and/ or hamartomas, accessory frenula, and alveolar anomalies) and variable digital defects such as polydactyly. The classification based on the presence of additional findings [Toriello, 1988, 1993] is not perfect, as many reported examples of a particular OFDS have some other condition. Here we describe six children, all diagnosed as having OFDS IV (OFDS with tibial defects), whose manifestations illustrate the apparent genetic heterogeneity.

Familial Pallister-Hall syndrome: case report and hormonal evaluation.

Pallister-Hall syndrome is a usually lethal dysplasia/malformation syndrome characterized by hypothalamic hamartoblastoma, hypopituitarism, postaxial polydactyly, craniofacial malformations, imperforate anus, and other malformations. We report a familial case in a male infant and his female sib fetus, suggesting autosomal recessive inheritance, or germinal mosaicism for an autosomal dominant mutation, or a segregating submicroscopic chromosome abnormality. Detailed endocrine evaluation on the surviving infant revealed documented pituitary function, pituitary deficit, and hypothalamic deficiency. We suggest that hypothalamic dysfunction contributes to the hypopituitarism seen in Pallister-Hall syndrome.

Ectrodactyly, ectodermal dysplasia, and cleft palate syndrome: report of a case with generalized telangiectasias.

The ectrodactyly, ectodermal dysplasia, and cleft palate syndrome is a rare type of ectodermal dysplasia. It usually occurs either as an autosomal dominant trait or in a sporadic form. We describe a neonate with this syndrome and generalized telangiectasias, an association that, to the best of our knowledge, has not been previously reported.

Long-term evaluation of a child with the branchio-oculo-facial syndrome.

We report on the 12-year development of a child with branchio-oculo-facial syndrome who was initially referred at age 5 months. Of note is his normal intelligence, regular class placement, hypernasal speech, and continued growth along the third centile. The importance of serial observations of patients with rare genetic disorders is emphasized.

Partial trisomy 11q in a female infant with Robin sequence and congenital heart disease.

We describe the clinical and cytogenetic findings in a female infant with partial trisomy 11q, Robin sequence, cardiac anomalies, and other minor malformations. We compare the phenotypic similarities of our case to a series by Pihko et al. (1981), who reported on 20 cases with partial trisomy 11q with similar associated craniofacial and cardiac defects. We conclude that genetic etiologies for patients diagnosed with the Robin sequence may be more common than previously believed and that initial karyotyping should be performed to aid both diagnosis and clinical management. In addition, the pattern of Robin sequence and cardiac defects may be specifically suggestive of partial trisomy 11q.

Strain difference in galactokinase level and susceptibility to the teratogenic effect of dietary galactose in mice: I. Teratogenic and embryopathic effect.

Congenital cataracts have been noted to occur in infants when either the mother or the mother and infant have reduced activity of the enzymes galactokinase (GK) or galactose-1-phosphate uridyl transferase (GALT). Studies were undertaken to elucidate the possible genetic and dietary fetomaternal interactions leading to the presumptive galactose teratogenesis noted in two inbred strains of mice differing in GK activity. Pregnant A/J (high erythrocyte GK activity 134.18 +/- 17.89 mU/gm Hb) and C57BL/6J (low erythrocyte GK activity 55.05 +/- 11.39 mU/gm Hb) mice were treated with a diet containing either 25% or 50% galactose throughout gestation. A significantly higher percentage of C57BL offspring (92.3%) were observed to have lens opacities when their mothers were fed a high-galactose diet, whereas no increase in lens pathology was observed in the offspring of similarly treated A/J mothers. Additionally, reciprocal matings were carried out so that all offspring were genetically equivalent in terms of GK activity. However, when the mother had low GK activity, a significant incidence of lens opacities was present in their offspring; this was not found when the mother had high GK activity. After weaning, no difference in the incidence of lens opacities was observed when the 25% galactose diet was introduced to the offspring of these reciprocal crosses, providing additional support for a maternal dietary influence on the development of lens opacities.

Blood product acquired HIV infection in children.

The medical community needs to ensure safety of blood and blood products. Blood bankers have instituted rigid criteria for exclusion of potential donors in high risk categories. Institution of HIV testing would appear to make blood products safer although the complete elimination of HIV contaminated blood and blood products may not be possible. The ELISA test is excellent for screening but misses approximately 1 in 200 (0.5%) HIV infected donors. Donor-screened, heat-treated factor VIII products appear to be quite effective in protecting the hemophilia population. However, we must continue to search for methodologies and techniques which will further guarantee blood product safety. The following methodologies have been suggested and warrant strong consideration: Vigilance in exclusion of potential high risk donors. Newer methodologies for retrovirus screening including the use of other surrogate markers. Institution of screening for HTLV-I and other retroviruses with attention to population surveillance for newer agents. Institution of cleaner methods of extracting specific blood components by monoclonal antibody techniques and DNA methodologies. For hemophiliacs, development of recombinant DNA products which by-pass the need for plasma derived clotting factors. It is predicted that such products should become available for use in about two years. In the interim, all clotting factors used should be donor-screened and virus-inactivated (by heat treatment, detergent washing and/or other newer methodologies). For the blood recipient, programs allowing for self donation prior to elective surgery and designated donors should be implemented. Although such programs may be logistically difficult, they should be given high priority.(ABSTRACT TRUNCATED AT 250 WORDS)

Human immunodeficiency virus (HIV) infection in children.

HIV infection in pediatric patients is a multisystem chronic disease that manifests as a clinical spectrum from asymptomatic infection through symptomatic infection with opportunistic infections and malignancies. The hematopoietic system is involved early in the systemic manifestations of this disease. The hematologic abnormalities seen are most probably a reflection of persistent viral infection, inflammation, and immune dysregulation, and may be complicated by secondary infections, chronic disease, drug toxicities, and nutritional deficiencies. Anemia and lymphopenia are commonly found in adult AIDS patients. Although both are also seen in pediatric patients, lymphopenia is much less common. Atypical lymphocytes with plasmacytoid characteristics have been identified in both adults and children. Pediatric bone marrow evaluation has shown an increase in plasma cells and plasmacytoid lymphocytes. Besides these findings, adult marrow findings include an increase in reticulum and lymphocytes appearing in a diffuse or aggregate pattern.

Difficulties in the prenatal diagnosis of Jarcho-Levin syndrome.

Prenatal diagnosis of Jarcho-Levin syndrome early in pregnancy has not been previously reported. We present a case in which ultrasound examination resulted in a tentative diagnosis at 22 weeks of pregnancy. The difficulties in arriving at a definite diagnosis are presented.

Inhibitors of coagulation in children.

Acquired inhibitors of coagulation factor interaction in nonhemophilic children are usually nonspecific, transient, and unassociated with clinical bleeding. They occur with some frequency and are the most common cause for a prolonged APTT found by routine testing. In children, some association with viral infections and treatment with penicillin has been noted, but their interrelationship with the development of antibodies remains unclear. The exact nature of these antibodies, usually directed against coagulant factor phospholipid, is not clear and multiple antibodies both specific as well as nonspecific may occur. No therapy is generally required. Rarely has the acute development of antibodies directed against specific coagulation factors occurred. The laboratory evaluation of the type of inhibitor is, therefore, most important as specific inhibitors may be associated with life-threatening bleeding situations. Their therapy should probably include attempts at eradication of the inhibitor by immunosuppressive agents or other newer modalities. Unfortunately, little information is available regarding the nature and outcome of specific inhibitors in children. Acquired inhibitors in hemophilic patients occur in about 6 to 10% of patients. Newer approaches to their therapy include activated PCC which have generally improved the outlook for such patients. Treatment regimens involve a knowledge of inhibitor response and the concomitant use of plasmapheresis, high-dose or continuous i.v. Factor VIII, and porcine Factor VIII, followed by activated PCC. The role of immunosuppressive agents and other newer modalities appears promising, however, prospective controlled studies are necessary to evaluate their role in the overall management of such patients.