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Thyroid function in very low birth weight infants: effects on neonatal hypothyroidism screening.

OBJECTIVES: To supply normative data for screening thyroxine (T4) and thyrotropin concentrations correlated with birth weight and age at screening of infants with birth weights ranging from 400 to 5500 gm, and to document the effects of screening of very low birth weight (VLBW) infants, because VLBW infants comprise 0.86% of surviving newborn infants and have very low total T4 concentrations with normal or elevated free T4 concentrations as a result of deficient protein binding of thyroid hormones. STUDY DESIGN: Both retrospective and prospective studies were used. We conducted retrospective analyses of screening of T4 and thyrotropin concentrations in 9,324 term, 18,946 low birth weight, and 3,450 VLBW infants in Massachusetts, and a prospective study of T4 and thyrotropin concentrations in 48 VLBW infants at 2 weeks of age. Forty of the infants also had hormone measurements at 4 weeks, 29 at 8 weeks of age, and 24 had analysis of cord blood samples. RESULTS: Median T4 concentrations for each weight group (in 250 gm increments) increased progressively and significantly up to 2500 gm. Of the surviving VLBW infants, 1.5% had screening T4 concentrations that were unmeasurably low (<3.9 nmol/L (0.3 microgram/dl)). The mean T4 concentration varied with age at screening, increasing from cord blood concentrations to a peak at 1 to 3 days of age and thereafter decreasing to a nadir at about 2 weeks in both low birth weight and VLBW infants. In VLBW infants the mean concentrations return to the level of 1 to 3 days by 4 to 8 weeks of age. The incidence of screening thyrotropin concentrations > or = 40 mU/L correlates inversely with weight. The incidence of early, transient hypothyroidism in VLBW infants defined by this thyrotropin concentration was eight times that in term infants. Two infants had late-onset, transient hypothyroidism at 2 and 7 weeks, respectively. CONCLUSIONS: The normative data related to birth weight and age at screening allow proper interpretation of VLBW results for primary T4 and primary thyrotropin screening programs. Screening of the concentrations of T4 and thyrotropin in VLBW increases the number of secondary measurements of T4 in a primary thyrotropin screening program and the number of secondary thyrotropin measurements in a primary T4 screening program by 6% and 9%, respectively. We recommend screening analyses for VLBW infants in the latter part of the first week of life and again at 2 and 4 to 6 weeks of age. This protocol would increase the number of screening analyses by 1.6%.

Birth Weight↗

Neonatal thyroid screening.

Recent advances in science and technology have led to the capability of early screening of newborn infants for congenital hypothyroidism. Preliminary screening programs in North America have been established in Quebec and in the Northwestern and Northeastern United States. To date these programs have screened approximately 750,000 newborn infants and detected 163 with congenital hypothyroidism. Preliminary information suggests that the early diagnosis and screening does in fact prevent mental retardation. Such programs appear to be economically sound in that they minimize the impact of congenital hypothyroidism on public budgets for care and rehabilitation of the mentally handicapped.

Canada↗

Neonatal hearing screening with otoscopy, auditory brain stem response, and otoacoustic emissions.

A study was performed to investigate the relationship between external and middle ear factors and hearing screening results by auditory brain stem response (ABR) and transient evoked otoacoustic emissions (EOAEs). The ears of 200 well newborns aged 5 hours to 48 hours underwent screening by ABR and EOAEs, followed by otoscopic examination. The pass rates for ABR and EOAE screening were 88.5% and 79%, respectively. On otoscopic examination, 13% (53 of 400) ears had occluding vernix obscuring the view of the tympanic membrane. Cleaning of vernix was attempted in ears that failed ABR or EOAE screening. Seventeen ears that failed ABR were cleaned, and 12 (71%) of them passed repeat ABR. Thirty-three ears that failed EOAE screening were cleaned, and 22 (67%) of them passed repeat emissions testing. Cleaning vernix increased the pass rates for ABR and EOAE screening to 91.5% and 84%, respectively. Decreased tympanic membrane mobility was found in 9% of ears that could be evaluated otoscopically. Increased failure rates for both ABR and EOAE screening were found in infant ears with decreased tympanic membrane mobility, but significance testing could not be performed because of inadequate sample size. Prevalence of occluding external canal vernix and middle ear effusion as a function of increasing infant age were studied. Implications for newborn hearing screening are discussed.

Body Fluids↗

Hepatitis C virus among childbearing women in Scotland: prevalence, deprivation, and diagnosis.

OBJECTIVES: (A) To examine the prevalence and demographic characteristics of hepatitis C virus (HCV) infection among childbearing women in Scotland; and (B) to determine the extent of maternal HCV infection diagnosed prior to birth. METHODS: (A) Residual dried blood spot samples from routine neonatal screening, collected throughout Scotland during March-October 2000, were unlinked from identifiers and tested anonymously for HCV antibodies; and (B) electronic record linkage of Scotland's databases of births and diagnosed HCV infections was performed. RESULTS: (A) Of 30,259 samples, 121 were enzyme linked immunosorbent assay repeat reactive and 88 of these were confirmed as anti-HCV positive in the recombinant immunoblot assay, representing a seroprevalence of 0.29-0.40%. HCV seroprevalence was high among 25-29 year olds (0.4-0.57%), in high deprivation areas (0.92-1.07%), and in Greater Glasgow (0.83-0.96%) and Grampian (0.38-0.62%). Adjusted relative risk for HCV infection was highest among residents in high deprivation areas of Glasgow (7.2 (95% confidence interval 2.0-25.5)). (B) Of 121 HCV infections found among women at delivery, 24% and 46% were estimated to have been diagnosed prior to pregnancy and birth, respectively. CONCLUSIONS: HCV prevalence among Scottish childbearing women is consistent with that expected from injecting drug use. Based on reported rates of mother to child transmission, 8-11 paediatric infections are expected per annum. Diagnosis in only 24% of infected women prior to pregnancy indicates the extent to which HCV goes unrecognised in the injecting community. The current HCV screening approach-to test only those with a history of injecting drug use (or other risk factors for infection)-identifies approximately a quarter of previously undetected infections among pregnant women.

Adult↗

Neonatal haemoglobinopathy screening.

The current practice of cord blood screening was found to be missing 14.3% of 'at risk' infants identified for screening in the antenatal period, largely due to failure of sample collection. The possibility of including haemoglobinopathy screening into the already established Guthrie card screening system for phenylketonuria and hypothyroidism was investigated, using haemoglobin electrophoresis on cellulose acetate membranes, citrate agar gel and isoelectric focussing in polyacrylamide gel. Denaturation of blood once dried onto filter paper made the standard electrophoresis techniques unsuitable, whilst isoelectric focussing gave clear separation of all bands and was therefore accepted as the method of choice.

Electrophoresis, Polyacrylamide Gel↗

On the nature of natural thymocytotoxic antibodies. A screening in neonatal, young, adult and pathological human sera.

The thymocytotoxic activity of human sera against guinea pig cells was earlier shown to be mediated by IgM and a heat-labile serum factor, presumably complement. It is not known if such natural cytotoxic activity represents background activity of preexisting clones of immunoglobulin-producing cells, cross-reacting antibodies appearing after immunization, physiological immune regulatory molecules, or components of an immune network. We have therefore examined the presence of thymocytotoxic IgM molecules in normal adult and neonatal sera and in a number of diseases which affect the lymphoid and immune system. The thymocytotoxic effect of serum was measured in different dilutions, both directly and after heat inactivation of the sera and supplementation with a standard amount of IgM-depleted serum, which is inactive in itself but provides a fixed amount of the heat-labile cofactor. The cytotoxic IgM was present in various amounts in all sera tested, although in neonates very small amounts were found. No specific aberration in toxic activity was seen in rheumatoid arthritis or a number of hematological diseases. In general, the cytotoxic activity correlated well with the total amount of IgM. However, in cases of chronic lymphocytic leukemia, idiopathic thrombocytopenic purpura and immunocytoma aberrant cytotoxic activities were found, but to ascertain a connection between these diseases and the factor would require a more extensive follow-up study. The results indicate that the naturally occurring thymocytotoxic IgM is widespread and may reflect a clone of B cells which is activated by an endogenous stimulus, or by some ubiquitous exogenous immunogen.

Adolescent↗

Genotypic confirmation from the original dried blood specimens in a neonatal hemoglobinopathy screening program.

Dried blood spots are used for newborn screening because of ease of sample collection, handling, and shipment. DNA is stable and accessible in the filter paper matrix. Genotypic confirmation using initial specimens is demonstrated for a regional screening program. Seventy-five blinded samples underwent DNA analysis after Hb electrophoresis. DNA was microextracted from a 1/2-inch semicircle (25 microL whole blood equivalent), amplified, and analyzed by four different methods. Direct amplification without microextraction and automated sequencing from microextracted DNA also was performed. All four analyses agreed for the A and S alleles in 70 of 75 specimens. Three disagreements were clarified by the other semicircle from the original sample: two were due to polymerase chain reaction contamination and one to contamination of one of four analytical tests. Two would have required analysis of a second specimen, one because of polymerase chain reaction failure and the second because the patient had S/beta-thalassemia. Direct amplification without microextraction was successful in an additional 77 of 78 specimens for analysis of the A, S, C, and E alleles. Automated direct sequencing from microextracted DNA was demonstrated for the A, S, and C alleles. Analysis of microextracted DNA from dried blood specimens for A and S alleles reduced the need for and costs of obtaining a second specimen for confirmation by 97%. Direct amplification without microextraction for analysis of A, S, and C alleles permits additional reduction in personnel time and costs. We have demonstrated that microextracted DNA is amenable to automated sequencing after asymmetric polymerase chain reaction. Direct genotypic confirmation can facilitate diagnosis and initiation of medical intervention.

Alleles↗

Ultrasound and neonatal hip screening. A prospective study of 'high risk' babies.

We describe a simple, quick ultrasound screening test for CDH, and its use in a prospective study of babies with a 'high risk' factor, over one year from January 1987. From a birth population of 3,879, 812 hip scans were performed on 406 babies and 98 babies were abnormal. So far, there have been no late cases of CDH. Family history, breech malposition, and postural foot deformities were confirmed to be important risk factors, but babies with a simple click were equally at risk. Our early results indicate that a large proportion of the potential late cases are contained within our extended high-risk group.

Hip Dislocation, Congenital↗