Differences in clinical condition and genotype at time of diagnosis of cystic fibrosis by newborn screening or by symptoms.

BACKGROUND: Early diagnosis through newborn screening (NBS) and early treatment of cystic fibrosis (CF) do lead to better prognosis. In the Netherlands, the median age for a clinical diagnosis is six months, and after newborn screening this is 30 days. It is unknown if being diagnosed at the age of six months or before two months leads to a clinically relevant difference of the clinical condition at the time of diagnosis. AIM: The aim of this study is to assess the differences in clinical parameters at diagnosis between children with CF identified by newborn screening (NBS) or by clinical diagnosis (CD) in the Netherlands. METHODS: From July 1st, 2007 to January 1st, 2012 all newly diagnosed CF patients were reported to the Dutch Paediatric Surveillance Unit (DPSU). All paediatricians received a questionnaire to collect data on mutations and clinical condition at diagnosis. Non-classical CF was excluded from the analysis on clinical condition. RESULTS: 204 new CF diagnoses were reported to the DPSU, 33 were reported twice and three had no CF after further testing. 127 questionnaires were returned (76%); 85 children were diagnosed because of clinical symptoms, 40 after NBS and two because of a positive family history. The median age at diagnosis was 34 weeks for a clinical diagnosis and 3 weeks after NBS. Non-classical CF was more prevalent in the NBS group (6 clinical, 14 NBS), mostly F508del/R117H7T (12). Compared to the NBS group, significantly more patients in the CD group showed failure to thrive, respiratory symptoms, and hospitalizations. 62% of the CD group showed abnormal signs at physical examination compared to 4% of the NBS group. CONCLUSION: At the time of diagnosis infants detected after NBS are in a significantly better condition than after a clinical diagnosis. Growth retardation is already seen when after NBS the diagnosis is confirmed, but NBS leads to a diagnosis before respiratory symptoms have developed.

First-trimester Down syndrome screening performance in the Dutch population; how to achieve further improvement?

OBJECTIVE: To study the performance of the first-trimester combined test between 2004 and 2006 compared to a previous period to investigate changes in time and identify reasons for sub-optimal performance. METHODS: Serum samples were analysed for pregnancy-associated plasma protein A (PAPP-A) and the free beta subunit of human chorionic gonadotrophin (f beta-hCG). Nuchal translucency (NT) was measured between 10 and 14 weeks. Tests were considered screen positive, if their calculated Down syndrome (DS) risk was at least 1 in 250 at term. RESULTS: A total of 20,293 singleton pregnancies were included in the analysis. The median maternal age fell from 35.7 to 34.3 years. The overall median weight-corrected multiple of the median (MoM) values of PAPP-A and f beta-hCG were 1.12 and 1.03, respectively. The median MoM value of NT was 0.89 and increased from 0.82 to 0.96. Sixty-six DS cases were detected by the screening test. The detection rate (DR) for DS was 75.9%, with a FPR of 3.3%. CONCLUSION: The performance of the first-trimester test has improved over the years. A better performance of the NT measurement was the main reason, although NT assessment should further be improved. In addition, a better setting of the medians for the biochemical parameters may contribute to a higher DR.

Neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in The Netherlands: the importance of enzyme analysis to ascertain true MCAD deficiency.

The outcome was determined of population-wide neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency using tandem mass spectrometry (MS/MS) in The Netherlands, between October 2003 and September 2005. Prospective population-wide neonatal screening for MCAD deficiency was performed in the northern part of The Netherlands. In newborns with blood octanoylcarnitine (C(8:0)) concentrations > or =0.3 micromol/L, clinical and laboratory follow-up was initiated, including MCAD enzymatic measurements which played a decisive role. In a 2-year period, 66 216 newborns were investigated for MCAD deficiency and follow-up was initiated in 28 newborns. True-positives (n = 14) were identified based upon MCAD enzyme activity <50%, measured with hexanoyl-CoA as substrate. The observed prevalence of MCAD deficiency was 1/6600 (95% CI: 1/4100-1/17 400). In addition to an elevated C(8:0) concentration, a C(8:0)/C(10:0) molar ratio >5.0 turned out to differentiate between false-positives and true-positives. Measurement of MCAD activity using phenylpropionyl-CoA as a substrate further discriminated between newborns with MCAD deficiency and so-called mild MCAD deficiency. To summarize, neonatal screening for MCAD deficiency in the northern part of The Netherlands resulted in the predicted number of affected newborns. Measurement of MCAD activity in leukocytes or lymphocytes using phenylpropionyl-CoA as a substrate can be regarded as the gold standard to diagnose MCAD deficiency upon initial positive screening test results.

Lack of standardization in determining gestational age for prenatal screening.

OBJECTIVES: To determine whether estimation of gestational age (GA) in the context of first-trimester Down syndrome screening is standardized in the Netherlands. METHODS: This was a retrospective study, carried out between January 2005 and December 2006, of women who underwent first-trimester Down syndrome screening (n = 40,730) based on GA, maternal serum analysis and nuchal translucency (NT) measurement. Date of the last menstrual period (LMP), dating scan information including measurement of crown-rump length (CRL), NT thickness and name of the sonographer were recorded for all pregnancies. The accuracy of estimation of GA was evaluated by comparing the GA based on the LMP with that estimated from the CRL, using relevant subsets of the database. A survey of 104 sonographers was performed to further investigate the findings of the preceding analysis. RESULTS: In 44% of all first-trimester combined tests the estimation of GA was based on the dating scan; the method of determination of GA was unknown in 23%. In 15% of all cases a dating scan was recorded but was not used to provide the estimation of GA at blood sampling. Detailed analysis showed that a consistent methodology for the estimation of GA from CRL was not maintained within hospitals and obstetric practices. For a single CRL, the reported GA differed by up to 10 days. Finally, it was demonstrated that individual sonographers reported different GAs for a given CRL. CONCLUSIONS: Currently, estimation of GA in the first trimester in the Netherlands is not standardized. To improve the performance of prenatal screening for Down syndrome, estimation of GA should be based on ultrasound examination, with one nationally accepted CRL curve.

First ISNS Reference Preparation for Neonatal Screening for thyrotropin, phenylalanine and 17alpha-hydroxyprogesterone in blood spots.

BACKGROUND: Neonatal screening for congenital disorders like phenylketonuria (PKU), congenital hypothyroidism (CH) and congenital adrenal hyperplasia (CAH) is generally performed in dried blood spots on filter paper. The analytes of interest for testing for PKU, CH and CAH are phenylalanine, thyrotropin (TSH) and 17alpha-hydroxyprogesterone (17OHP), respectively. The International Society for Neonatal Screening (ISNS) decided to prepare a combined reference preparation for the three analytes on filter paper Schleicher & Schuell #903, Whatman BFC180 and Toyo Roshi 545. This 'First ISNS Reference Preparation for Neonatal Screening for TSH, phenylalanine and 17OHP in blood spots' (1st ISNS-RPNS) has been prepared by the RIVM (Bilthoven). METHOD: The number of filter paper cards prepared, each with two sets of six blood spot calibrators, was 480, 42 and 69 for Schleicher & Schuell #903, Whatman BFC180 and Toyo Roshi 545, respectively. The volume of blood dispensed was 50 microl. The range of concentrations for TSH was 1-121 mIU/L blood, for phenylalanine 65-865 micromol/L blood and for 17OHP 2.2-302 nmol/L blood. RESULTS: The linearity of the blood spot calibrators and the homogeneity of the batch (only tested for Schleicher & Schuell) were good. The differences between the three filter papers were small: i.e. the potency of the ISNS-RPNS on Whatman and Toyo Roshi in terms of Schleicher & Schuell was between 0.98 and 1.09 for the three analytes. CONCLUSION: The 1st ISNS-RPNS for TSH, phenylalanine and 17OHP can be said to be suitable as formal reference preparation and as a source for (re)calibrating kit calibrators.

A pilot study to estimate incidence of guanidinoacetate methyltransferase deficiency in newborns by direct sequencing of the GAMT gene.

BACKGROUND: GAMT deficiency is an autosomal recessive disorder of creatine biosynthesis causing developmental delays or intellectual disability in untreated patients as a result of irreversible brain damage occurring prior to diagnosis. Normal neurodevelopmental outcome has been reported in patients treated from neonatal period highlighting the importance of early treatment. METHODS: Five hundred anonymized newborns from the National Newborn Screening Program of The Netherlands were included into this pilot study. Direct sequencing of the coding region of the GAMT gene was applied following DNA extraction. The disease causing nature of novel missense variants in the GAMT gene was studied by overexpression studies. GAA and creatine was measured in blood dot spots. RESULTS: We detected two carriers, one with a known common (c.327G>A) and one with a novel mutation (c.297_309dup (p.Arg105Glyfs*) in the GAMT gene. The estimated incidence of GAMT deficiency was 1:250,000. We also detected five novel missense variants. Overexpression of these variants in GAMT deficient fibroblasts did restore GAMT activity and thus all were considered rare, but not disease causing variants including the c.131G>T (p.Arg44Leu) variant. Interestingly, this variant was predicted to be pathogenic by in silico analysis. The variants were included in the Leiden Open Variation Database (LOVD) database (www.LOVD.nl/GAMT). The average GAA level was 1.14µmol/L±0.45 standard deviations. The average creatine level was 408µmol/L±106. The average GAA/creatine ratio was 2.94±0.136. CONCLUSION: The estimated incidence of GAMT deficiency is 1:250,000 newborns based on our pilot study. The newborn screening for GAMT deficiency should be implemented to identify patients at the asymptomatic stage to achieve normal neurodevelopmental outcome for this treatable neurometabolic disease. Biochemical investigations including GAA, creatine and GAMT enzyme activity measurements are essential to confirm the diagnosis of GAMT deficiency. According to availability, all missense variants can be assessed functionally, as in silico prediction analysis of missense variants is not sufficient to confirm the pathogenicity of missense variants.

Spontaneous dissociation of human pituitary luteinizing hormone in solution.

Aliquots of a solution of highly purified human pituitary LH (hLH) were incubated with variations in temperature and time. The incubates were chromatographed on Sephadex G-100 as well as on DEAE-Sephadex A25. The column effluents were assayed in radioligand assay and in specific hLH alpha- and hLH beta-RIA systems. The results indicate that there is spontaneous dissociation of hLH at elevated temperatures under otherwise "normal" conditions concerning, for example, pH and ionic strength. The degree of dissociation is both time and temperature dependent. This dissociation is not due to proteolytic enzymes. It is concluded that one should be alert when using hLH subunit RIA systems at elevated temperatures for measuring hLH levels, e.g. in clinical samples, because artificial high levels may be obtained.

The effects of bromocriptine, thyrotropin-releasing hormone, and gonadotropin-releasing hormone on hormone secretion by gonadotropin-secreting pituitary adenomas in vivo and in vitro.

The characteristics and dynamics of hormone secretion in vivo and in vitro were investigated in six patients with gonadotropin-secreting pituitary adenomas. All six tumors secreted and contained FSH and different combinations of LH, beta-LH, and alpha-subunit. In addition, immunohistochemical examination of the pituitary tumor tissue showed staining with both LH and FSH in three and either LH or FSH in the other three tumors. TRH and GnRH stimulated hormone secretion in vivo and in vitro, and they also increased the hormone content of the cultured tumor cells. Bromocriptine significantly inhibited hormone release and reduced the hormone content of the tumor cells. In vivo, 2.5 mg bromocriptine significantly suppressed plasma hormone levels; the inhibiting effect on alpha-subunit concentrations was in general more marked than that on LH and FSH. We conclude that hormone release by gonadotropin-secreting pituitary adenomas can be stimulated by TRH and GnRH and inhibited by bromocriptine. Most of these tumors synthesize FSH, but there is a wide variation in the production of LH, beta-LH, and alpha-subunits. The sensitivity of hormone release to bromocriptine suggests that chronic therapy with this drug might have a beneficial effect on pituitary tumor size.

Accreditation of medical laboratories in The Netherlands.

Among the medical laboratory professionals, a growing interest exists in the systematic application of quality assurance to their own practice, and consequently in The Netherlands, there is an increasing request for an official accreditation of the quality management system and the competence of the professionals through Coordinatie Commissie voor Kwaliteitsbewaking in Laboratoria in de gezondheidszorg (CCKLtest), the Dutch Accreditation Board for Medical Laboratories. This article gives an overview of the current situation in The Netherlands; regarding the standards, the rules for accreditation, the training and selection assessors and what meanwhile is achieved. Since 1994, 60 clinical laboratories have been recognized by CCKLtest and another 40 laboratories have requested accreditation and are waiting for the inspection in 2001. Thus, 25% of all clinical laboratories in The Netherlands will be inspected within the current year.

The concentration of morphine in serum of rats made dependent using a drug-admixed food method.

The present study reports on the induction of physical dependence in rats using morphine-admixed food and addresses the question of the resulting concentration of morphine in serum. The stability of morphine in food is good, since no decrease in concentration could be observed. The concentration of morphine in serum during the experiment was measured using a radioimmunoassay technique. A correlation was found between the food intake during a 7-hour period and the concentration of morphine in the serum at the end of that period, both for a 1 g/kg and a 2 g/kg batch of morphine-admixed food. The concentration of morphine in serum was also found to be dose-related during a period of 6-23 days when the rats were fed for a prolonged period. After long-term administration of 1 g/kg morphine in food a steady-state level of about 0.5 mg/l serum was obtained. Similarly with 2 g/kg morphine in food a steady-state level of 0.8-1.1 mg/l serum was reached. After withdrawal of morphine the serum concentration of morphine dropped to 0.1 mg/l within 24 hours and to below the detection limit within 48 hours. During the withdrawal period sharp drops were noted in body weight (20%) and food intake (50%) after one day.

The need for standardized bloodspot TSH-calibrators in congenital hypothyroidism screening.

INTRODUCTION: The preparation of bloodspot calibrators and quality control samples for neonatal thyrotropin (TSH), as part of the national quality assessment scheme in The Netherlands, is sometimes problematic. Often, the recovery of the added TSH is well above 100% when measured in plasma. Results from other External Quality Assessment Schemes for neonatal TSH show similar problems. METHODS AND RESULTS: A questionnaire was sent to 17 kit manufacturers and organizers of EQAS concerning the preparation of bloodspot calibrators for TSH; 13 completed questionnaires were returned. There are large differences with respect to type of filterpaper, matrix, assessment of TSH-concentrations to the calibrators, size of the bloodspots, shelf life, etc. DISCUSSION: Attention is focused on several items to be considered when attempting standardization of the preparation of TSH bloodspot calibrators.

Effect of sodium bromide on endocrine parameters in the rat as studied by immunocytochemistry and radioimmunoassay.

Male rats were fed a normal or sodium bromide-enriched diet for 4 or 12 weeks. Sodium bromide concentrations were 0, 20, 75, 300, 1200 and 19,200 mg/kg diet. At the end of the experiments the pituitary gland, thyroid and testes were examined by histopathological and immunocytochemical techniques, while serum hormone levels were established by radioimmunoassay. Histopathological examination revealed an activation of the thyroid and a decreased spermatogenesis in the testes in the highest dose group. Using immunocytochemical techniques a decrease was noted in the amount of thyroxine in the thyroid. No effect was found in growth hormone-producing cells in the pituitary gland, while immunoreactivity for thyroid-stimulating hormone and for adrenocorticotropic hormone was increased. The concentration of thyroxine, testosterone and corticosterone in the serum appeared to be decreased. Due to feedback regulation, the pituitary gland was stimulated to produce and release thyroid-stimulating hormone, follicle-stimulating hormone, adrenocorticotropic hormone and insulin, whereas the release of growth hormone was suppressed. Most of these changes were restricted to rats on the highest treatment level. It is concluded that sodium bromide, at least in high doses, directly disturbs the function of the thyroid, testes and adrenals.

Four-week toxicity study of phenyl isothiocyanate in rats.

In a subacute toxicity study, phenyl isothiocyanate (PIT) was administered to male rats on 5 days/wk by gastric intubation at dose levels of 0, 2.5, 10 and 40 mg/kg body weight/day for 4 wk. Body-weight gain was recorded weekly and a complete haematological examination and determinations of alanine aminotransferase, aspartate aminotransferase and thyroxine in serum were performed. The heart, liver, spleen, kidneys, thyroid, adrenals and mesenteric lymph nodes were weighed and examined microscopically. In the highest dose group, slightly decreased growth and a statistically significant increase in mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration were noted. Relative heart, liver, kidney and adrenal weights also showed a statistically significant increase in the highest dose group. Total serum thyroxine and free thyroxine were decreased in the groups given 10 or 40 mg PIT/kg. Microscopic examinations revealed no abnormalities. The measurement of the serum thyroxine concentration appeared to be the most sensitive indicator of an effect in this experiment.

The influence of sodium bromide in man: a study in human volunteers with special emphasis on the endocrine and the central nervous system.

Sodium bromide was administered orally in capsules to healthy volunteers in doses of 0, 4 or 9 mg Br-/kg/day using a double-blind design. Each treatment was given to seven males for 12 weeks and to seven non-pregnant females (not using oral contraceptives) over three full cycles. Special attention was paid to possible effects on the endocrine and central nervous systems. At the start and end of the study, a full medical history, the results of a physical examination, haematological studies and standard clinical chemistry and urine analyses were recorded for each subject. These showed no changes for individuals following treatment, except for some incidence of nausea associated with bromide-capsule ingestion. Mean plasma-bromide concentrations at the end of treatment were 0.08, 2.14 and 4.30 mmol/litre for males and 0.07, 3.05 and 4.93 mmol/litre for females of the 0-, 4- and 9-mg Br-/kg/day groups, respectively. Plasma half-life was about 10 days. In the females taking 9 mg Br-/kg/day (but in no other group) there was a significant (P less than 0.01) increase in serum thyroxine and triiodothyronine between the start and end of the study but all concentrations remained within normal limits. No changes were observed in serum concentrations of free thyroxine, thyroxine-binding globulin, cortisol, oestradiol, progesterone or testosterone, or of thyrotropin, prolactin, luteinizing hormone (LH) and follicle-stimulating hormone before or after the administration of thyrotropin-releasing hormone and LH-releasing hormone. Analysis of neurophysiological data (EEG and visual evoked response) showed a decrease in delta 1- and delta 2-activities and increases in beta-activities and in mean frequency (Mobility parameter) in the groups on 9 mg Br-/kg/day, but all the findings were within normal limits.

Chronic toxicity and carcinogenicity of bis(tri-n-butyltin)oxide (TBTO) in the rat.

In a 106-wk toxicity and carcinogenicity study, groups of 60 male and 60 female weanling Wistar rats were fed 0, 0.5, or 50 mg bis(tri-n-butyltin)oxide (TBTO)/kg diet. In males, feed consumption was increased in all treated groups and increased water consumption occurred at 5 and 50 mg/kg. During the second year, body weight decreased in the 50-mg/kg males, while the females in that group showed no weight gain. Excess mortality was confined to the 50-mg/kg group towards the end of the study. Haematological changes, comprising anaemia, lymphocytopenia and thrombocytosis were noted mainly at the high-dose level. Also, signs of decreased kidney function and increased plasma enzyme activities (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) were noted. No effects on serum hormone concentrations (thyrotropin, follicle stimulating hormone, luteinizing hormone or insulin) were observed, except for a decrease in the free thyroxin:thyroxin ratio in both sexes at the high-dose level. Higher serum IgM and IgA levels were present at 50 mg/kg, while, in females, IgG was decreased. At 50 mg/kg, the ovaries, adrenals, spleen (females), heart (males), pituitary, liver and kidneys were increased in weight, but the thyroid weight was decreased in females. The total tin concentrations in liver and kidneys showed a dose relationship and, in general, the concentrations were similar after 1 and 2 yr. Non-neoplastic histological alterations after 1 yr consisted of a decrease in the cell height of the thyroid follicles in all dose groups, with a reduced number of psammoma bodies at 50 mg/kg, a decrease in splenic iron content at 5 (females only) and 50 mg/kg, and a slight bile-duct activation. After 2 yr, only the thyroid changes were still present. In addition, at 2 yr, vacuolation and pigmentation of the proximal tubular epithelium and nephrosis were enhanced at 50 mg/kg. The incidence of benign tumours of the pituitary was significantly elevated and enhanced at 0.5 and 50 mg/kg. At 50 mg/kg increases in pheochromocytomas in the adrenal medulla and in parathyroid adenomas (males) were noted, while adrenal cortical tumours were decreased (males). There was a low, non-dose-related incidence of pancreatic carcinoma. Other tumour rates were in line with control data. It is concluded that lifetime feeding of 50 mg TBTO/kg diet induces toxicity in various organ systems. An increase in some common tumours was found at the high dose, probably due to hormonal or immunological changes.(ABSTRACT TRUNCATED AT 400 WORDS)

[Evaluation of the hepatitis B prevention program in newborn infants. I. National data, 1990]. / Evaluatie van het hepatitis B-preventieprogramma bij pasgeborenen. I. Landelijke gegevens, 1990.

OBJECTIVE: To evaluate the effectiveness of the national programme for prevention of perinatal hepatitis B infections. SETTING: The regional public health laboratories and provincial immunization administrations in the Netherlands. DESIGN: Retrospective evaluation. METHODS: Starting October 1989 routine screening of pregnant women for HBsAg was performed and passive-active immunisation of infants of HBsAg-positive mothers was added to the national immunisation programme. Infants receive hepatitis B immunoglobulin at birth and hepatitis B vaccine at 3,4,5, and 11 months of age, concomitant with the DTP-polio vaccine. The effectiveness of screening and intervention in 1990 was evaluated. RESULTS: Screening covered about 85% of the pregnant population and the prevalence (0.44%) was less than expected. About 60% of the infants born to HBsAg-positive mothers were registered for vaccination. Of these infants the average coverage was 83% for immunoglobulin, and 90%, 86%, 80% and 55% for the four successive hepatitis B vaccinations. There was considerable delay in vaccine administration; frequently doses were administered later than recommended. CONCLUSION: Compliance with screening and vaccination appeared incomplete. Recommendations for the simplification of the current programme are made.

[Evaluation of a decade of neonatal screening for congenital hypothyroidism in The Netherlands]. / Evaluatie van een decennium neonatale screening op congenitale hypothyreoïdie in Nederland.

OBJECTIVE: Evaluation of the Dutch screening programme for congenital hypothyroidism (CH). DESIGN: Descriptive. SETTING: Nationwide. METHODS: Data on the screening were obtained from the administration body for vaccination and screening results, laboratories and paediatricians to whom infants with positive screening values were referred, during the period from January 1st, 1981 to December 31st, 1990. RESULTS: Of all live births in the Netherlands, 99.5% (1,797,719) were screened for CH. During the study period, 10,165 children (0.57% of all screened infants) were referred. Of the referred children, 529 had primary CH and 53 had congenital thyrotropin deficiency syndrome (CTDS). The prevalences of primary CH and CTDS are 1:3,400 and 1:25,000, respectively. The sensitivity of the programme with respect to detection of primary CH and CTDS was 99% and 74%, respectively. For all forms of CH combined, the specificity of the programme was 99% and the positive predictive value 6%. The positive predictive value was especially low in the group of infants with low T4 and normal thyrotropin values. One of the goals of the programme is to realise the start of treatment in all patients before they reach the age of three weeks. Before the screening programme came into being, the cumulative proportion of patients treated on the 21st day was 6%. After the beginning of the programme, the proportion increased to 54%. In screened patients with a severe form of CH it is currently 72%. CONCLUSION: The screening programme has made a substantial and important contribution to early and effective identification of patients with CH. A number of measures to decrease the number of false-positive results have been taken and others are at present being investigated. Although patients are now treated much earlier than before the programme started, substantial improvement in this respect is still possible. This can only be achieved by a collective effort of performers of the heel puncture, laboratories, administration body for vaccination and screening results, general practitioners and pediatricians.

Parental knowledge reduces long term anxiety induced by false-positive test results after newborn screening for cystic fibrosis.

BACKGROUND: False-positive screening results in newborn screening for cystic fibrosis may lead to parental stress, family relationship problems and a changed perception of the child's health. AIM OF THE STUDY: To evaluate whether parental anxiety induced by a false positive screening result disappears after six months and to assess whether a special program to inform parents prior and during the screening procedure prevents or diminishes parental anxiety. METHODS: Prospective controlled study assessing the long term effects of false-positive test results of newborn screening for cystic fibrosis (NBSCF) on parental anxiety and stress by means of questionnaires sent to parents of 106 infants with a false positive newborn screening test and 318 randomly selected infants with a true negative screening test. Additionally we interviewed 25 parents of the false-positive group. RESULTS: Parents showed negative feelings after being informed about the positive screening test result. After confirmation that their child was healthy and not suffering from CF, most parents felt reassured. After six months no difference in anxiety levels between both groups of parents was found. Well-informed parents in the false positive group experienced less stress. CONCLUSIONS: A positive screening test result induces parental anxiety but false positive test results in NBSCF do not seem to cause long-term anxiety. Well-informed parents show lower stress and anxiety levels.

Evolution of an influenza pandemic in 13 countries from 5 continents monitored by protein microarray from neonatal screening bloodspots.

BACKGROUND: Because of lack of worldwide standardization of influenza virus surveillance, comparison between countries of impact of a pandemic is challenging. For that, other approaches to allow internationally comparative serosurveys are welcome. OBJECTIVES: Here we explore the use of neonatal screening dried blood spots to monitor the trends of the 2009 influenza A (H1N1) pdm virus by the use of a protein microarray. STUDY DESIGN: We contacted colleagues from neonatal screening laboratories and asked for their willingness to participate in a study by testing anonymized neonatal screening bloodspots collected during the course of the pandemic. In total, 7749 dried blood spots from 13 countries in 5 continents where analyzed by using a protein microarray containing HA1 recombinant proteins derived from pandemic influenza A (H1N1) 2009 as well as seasonal influenza viruses. RESULTS: Results confirm the early start of the pandemic with extensive circulation in the US and Canada, when circulation of the new virus was limited in other parts of the world. The data collected from sites in Mexico suggested limited circulation of the virus during the early pandemic phase in this country. In contrast and to our surprise, an increase in seroprevalence early in 2009 was noted in the dataset from Argentina, suggestive of much more widespread circulation of the novel virus in this country than in Mexico. CONCLUSIONS: We conclude that this uniform serological testing of samples from a highly standardized screening system offers an interesting opportunity for monitoring population level attack rates of widespread diseases outbreaks and pandemics.