Ulrike Steuerwald - Academia.edu (original) (raw)

Papers by Ulrike Steuerwald

Research paper thumbnail of Körpervorstellungen von Kindergartenkindern

Klinische Padiatrie, 1983

: Both from the view of the pediatrician (16) and the child analyst (3, 6, 9, 21), and recently, ... more : Both from the view of the pediatrician (16) and the child analyst (3, 6, 9, 21), and recently, too, by behavioral biologists (15) the emotional aspects of illness and hospitalization have been treated with increasing differentiation. On the other hand there are only few studies regarding the cognitive aspects of the problem, i.e. the concepts children have of their bodies and of illness, which depend on the momentary level of their intellectual development. Children's ideas and fears arising from illness or hospitalization frequently can only be understood with the knowledge of the actual body-image. Therefore we have tried to investigate by interviews and drawings of three- to seven-year-old preschoolers their conceptions of the interior of the body and its function. The sources of these ideas were discussed and some suggestions were made how the results of the study could be used in hospital and kindergarten.

Research paper thumbnail of EDTA in Dried Blood Spots Leads to False Results in Neonatal Endocrinologic Screening

BACKGROUND: Blood samples for neonatal screening for inborn errors of metabolism are collected an... more BACKGROUND: Blood samples for neonatal screening for inborn errors of metabolism are collected and shipped on standardized filter paper cards. Occasionally these samples are contaminated with EDTA, which is often used for anticoagulation. EDTA may interfere with newborn screening tests based on lanthanide fluorescence and thus lead to false-negative or false-positive results.

Research paper thumbnail of Asthma and allergy in children with and without prior measles, mumps, and rubella vaccination

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, Jan 3, 2015

The existing literature on the association between measles vaccination and subsequent risk of all... more The existing literature on the association between measles vaccination and subsequent risk of allergic disease is inconclusive. The aim of this study was, therefore, to determine whether measles, mumps and rubella (MMR) vaccination administered in early childhood was associated with asthma and allergic diseases at ages 5, 7 and 13 years in a birth cohort. In the Faroe Islands, 640 children were followed from birth. Follow-up examinations at ages 5, 7 and 13 years included a physical examination and a maternal questionnaire about the child's health. At age 7, total and grass-specific IgE was quantified in the child's serum, and at age 13, the children underwent skin prick tests (SPT). The child's vaccination card was reviewed at examinations. At age 5, 533 of 555 children had been vaccinated for MMR. After confounder adjustment we found early life MMR vaccination to be associated with a two-third reduction in the odds of asthma (OR: 0.33, 95% CI: 0.12; 0.90) and hypersens...

Research paper thumbnail of Application of a second-tier newborn screening assay for c5 isoforms

JIMD reports, 2014

We report a case of false-positive metabolic screening for isovaleric acidemia in a newborn due t... more We report a case of false-positive metabolic screening for isovaleric acidemia in a newborn due to treatment of the mother with pivalic acid containing antibiotics before delivery. By using a recently established second-tier test based on the tandem-MS technique, we could identify pivalic acid in a dried blood sample taken during routine neonatal screening. Before this second-tier test was initiated, diverse analytical procedures were performed in the baby to rule out isovaleric acidemia and carnitine supplementation was started. This caused additional psychological burden to the family. The direct use of the second-tier test would have avoided these negative consequences of a false-positive screening result.

Research paper thumbnail of Neonatal screening for citrullinaemia

European journal of pediatrics, 2003

In a period of 40 months (1st March 1999 to 30th June 2002) 610,000 blood samples were analysed i... more In a period of 40 months (1st March 1999 to 30th June 2002) 610,000 blood samples were analysed in one screening centre for citrulline as a pilot study for neonatal screening using tandem mass spectrometry. Persistent hypercitrullinaemia (Cit >1.5 mg/dl or 85.5 micro mol/l, not corrected for recovery) was identified in 15 newborns. Four children were diagnosed with classical neonatal onset citrullinaemia and eight with persisting asymptomatic hypercitrullinaemia. In two asymptomatic newborns and in one symptomatic preterm patient, argininosuccinate lyase deficiency was identified as the cause of moderately elevated levels of citrulline (cases not described in this paper). Citrulline concentrations were only temporarily mildly elevated in two newborns and in these the results of the original neonatal screening were therefore regarded as false-positive; we did not find any other false-positives. The screening result allowed the introduction of immediate specific treatment in two ca...

Research paper thumbnail of Tandemmassenspektrometrie

Monatsschrift Kinderheilkunde, 2000

Research paper thumbnail of Neurobehavioral performance of Inuit children with increased prenatal exposure to methylmercury

International Journal of Circumpolar Health, 2002

Exposure to methylmercury from marine mammals and other seafood may affect the development of the... more Exposure to methylmercury from marine mammals and other seafood may affect the development of the central nervous system. In a traditional Inuit community in Qaanaaq, Greenland, mercury concentrations in cord blood and maternal hair have been examined in connection with all births. We examined 43 children at age 7-12 years with a battery of neurobehavioral tests. The average mercury concentration in hair was 5.0 microg/g and 1.5 microg/g in children and mothers, respectively. Clinical neurological examination did not reveal any obvious deficits. However, neuropsychological tests showed possible exposure-associated deficits, though only in a few cases reaching statistical significance. In conjunction with data from other studies, peak latencies on brainstem auditory evoked potentials tended to be prolonged at increased exposure levels. The data from the present study therefore appears in accordance with other evidence that prenatal or early postnatal exposures to methylmercury may cause subtle neurobehavioral deficits.

Research paper thumbnail of Attenuated growth of breast-fed children exposed to increased concentrations of methylmercury and polychlorinated biphenyls

The FASEB Journal, 2003

Breast-feeding has been linked to slowed postnatal growth. Although the basis for this &a... more Breast-feeding has been linked to slowed postnatal growth. Although the basis for this "weanling's dilemma" is unclear, environmental contaminants in human milk may be of relevance. We studied a Faroese birth cohort of 182 singleton children, born at term in 1994-95. Concentrations of mercury in cord blood and of polychlorinated biphenyls in maternal milk were measured, and duration of breast-feeding was recorded. At 18 months, children who had been exclusively breast-fed for at least 6 months weighed 0.59 kg less [95% confidence interval (CI) = 0.03, 1.16 kg] and were 1.50 cm [95% CI = 0.52, 2.47 cm] shorter than those not breast-fed. However, calculated transfer of contaminants from human milk fully explained the attenuated growth. Irrespective of duration of breast-feeding, a doubling of the mercury concentration in cord blood was associated with a decrease in weight at 18 months by 0.19 kg (95% CI = 0.03, 0.35 kg) and in height by 0.26 cm (95% CI = -0.02, 0.55 cm). Weight and height at 42 months showed the same tendencies, but the main effect occurred before 18 months of age. Thus, in communities with increased contaminant exposures, risks associated with lactational transfer of toxicants to the infant must be considered when judging the benefits of prolonged breast-feeding.

Research paper thumbnail of Rapid steroid hormone quantification for congenital adrenal hyperplasia (CAH) in dried blood spots using UPLC liquid chromatography–tandem mass spectrometry

Steroids, 2011

Newborn screening for congenital adrenal hyperplasia (CAH) is usually done by quantifying 17α-hyd... more Newborn screening for congenital adrenal hyperplasia (CAH) is usually done by quantifying 17α-hydroxyprogesterone using immunoassay. However, this test produces high rates of false positive results caused by cross reacting steroids. Therefore we have developed a selective and specific method with a short run time (1.25 min) for quantification of 17α-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, 11-deoxycorticosterone and cortisol from dried blood spots. The extraction procedure is very simple and steroid separation is ensured on a BEH C18 column and an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Analysis was done in positive ionization mode (ESI+) and recorded in multiple reaction monitoring mode (MRM). The method gave linear results for all steroids over a range of 5-200 (cortisol: 12.5-500)nmol/L with coefficients of regression >0.992. Absolute recovery was >64.1%. Across the analytical range the inter-assay coefficient of variation (CV) was <3%. Newborn blood samples of patients with confirmed 21-CAH and 11-CAH could clearly be distinguished from samples of unaffected newborns falsely positive on immunoassay. The method is not influenced by cross reactions as found on immunoassay. Analysis of dried blood spots shows that this method is sensitive and fast enough to allow rapid analysis and can therefore improve the newborn screening program.

Research paper thumbnail of Neonatal screening for defects of the mitochondrial trifunctional protein

Molecular Genetics and Metabolism, 2005

Long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deWciency has been included in the routine n... more Long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deWciency has been included in the routine neonatal screening program by the German screening commission. As tandem mass spectrometry (TMS) does not discriminate between the diVerent defects of the mitochondrial trifunctional protein (MTP) screening for isolated LCHAD deWciency includes the detection of long-chain 3-ketoacyl-CoA thiolase and complete MTP deWciencies as well. We identiWed 11 patients with abnormalities of the MTP out of 1.2 million newborns screened in our laboratory during the last 6 years. Treatment was started on the day the screening result was obtained (day 3 to day 9 of life). Seven of these newborns developed satisfactorily during an observation period of up to 64 months. They had isolated LCHAD deWciency, four of them caused by the typical mutation (1528 G>C), three others had no molecular genetic analysis done or were shown to have previously unknown mutations. Four children did not survive, two of them showing complete deWciency of MTP and two showing deWciency of long-chain 3-ketoacyl-CoA thiolase. We conclude that, despite the rarity of the disease, screening for MTP deWciencies is justiWed based on the following criteria: improved quality of life for patients with isolated LCHAD deWciency, absence of stigmatisation of babies showing mild variants without necessity of treatment, no signiWcant increase of the total number of false positive screening results, no false negative results to our knowledge. Finally, extension of analysis to MTP deWciencies is achieved without additional costs for screening laboratories already using TMS.  (J. Sander).

Research paper thumbnail of Dystonia and deafness due to SUCLA2 defect; Clinical course and biochemical markers in 16 children

Mitochondrion, 2009

Patients with SUCLA2 gene defects characteristically develop the trias of early hypotonia, progre... more Patients with SUCLA2 gene defects characteristically develop the trias of early hypotonia, progressive dystonia and sensori-neural deafness. We describe the clinical course and biochemical phenotype in 16 children from the Faroe Islands with a homozygous SUCLA2 splice site mutation. Elevated urinary 3-hydroxyisovaleric acid is a novel biochemical feature in patients. Progressive hearing loss, in combination with a characteristic metabolite profile (increased lactate, methylmalonic acid, C4-dicarboxylic carnitine, 3-hydroxyisovaleric acid) should lead the clinician to the correct diagnosis even in patients with only intermittent lactic acidemia. Direct SUCLA2 sequence analysis is suggested instead of an invasive muscle biopsy to obtain the diagnosis. Nutritional intervention may be considered in SUCLA2 patients.

Research paper thumbnail of Maternal seafood diet, methylmercury exposure, and neonatal neurologic function

The Journal of Pediatrics, 2000

Objective: To determine whether neonatal neurologic function is adversely affected b X seafood co... more Objective: To determine whether neonatal neurologic function is adversely affected b X seafood contaminants from maternal diet during pregnancy.

Research paper thumbnail of Birthweight in a fishing community: significance of essential fatty acids and marine food contaminants

International Journal of Epidemiology, 2001

Research paper thumbnail of Neonatal Screening: Identification of Children with 11ß-Hydroxylase Deficiency by Second-Tier Testing

Hormone Research in Paediatrics, 2012

21-Hydroxylase deficiency (21-OHD) is the target disease of newborn screening for congenital adre... more 21-Hydroxylase deficiency (21-OHD) is the target disease of newborn screening for congenital adrenal hyperplasia (CAH). We describe the additional detection of patients suffering from 11β-hydroxylase deficiency (11-OHD) by second-tier testing. Over a period of 5 years, screening for CAH was done in a total of 986,098 newborns by time-resolved immunoassay (DELFIA®) for 17α-hydroxyprogesterone (17-OHP). Positive samples were subsequently analyzed in an LC-MS/MS second-tier test including 17-OHP, cortisol, 11-deoxycortisol, 4-androstenedione and 21-deoxycortisol. In addition to 78 cases of 21-OHD, 5 patients with 11-OHD were identified. Diagnostic parameters were a markedly elevated concentration of 11-deoxycortisol in the presence of a low level of cortisol. Androstenedione was also increased. In contrast to 21-OHD, concentrations of 21-deoxycortisol were normal. Steroid profiling in newborn blood samples showing positive results in immunoassays for 17-OHP allows for differentiating 21-OHD from 11-OHD. This procedure may not detect all cases of 11-OHD in the newborn population because there may be samples of affected newborns with negative results for 17-OHP in the immunoassay.

Research paper thumbnail of Neonatal screening for medium chain acyl-CoA deficiency: high incidence in Lower Saxony (northern Germany)

European Journal of Pediatrics, 2001

Research paper thumbnail of Molecular genetic basis and prevalence of glycogen storage disease type IIIA in the Faroe Islands

European Journal of Human Genetics, 2001

Glycogen storage disease type IIIA (GSD IIIA) is caused by mutations of the amyloglucosidase gene... more Glycogen storage disease type IIIA (GSD IIIA) is caused by mutations of the amyloglucosidase gene (AGL). For most populations, none of the AGL mutations described to date is particularly frequent. In this paper, we report that six children with GSD IIIA from the Faroe Islands were found to be homozygous for the novel nonsense mutation c.1222C>T (R408X) of the AGL gene. This mutation is easily detected by restriction enzyme digest with NsiI after mismatch PCR. Investigating five intragenic polymorphisms, we could show that this mutation was always associated with the same haplotype. The c.1222C>T mutation could be detected on two chromosomes of another 50 unselected GSD IIIA patients of other European or North American origin which means that this mutation plays a minor role worldwide. From the fact that we are currently aware of a total of 14 GSD IIIA cases in the Faroese population of 45 000, the observed prevalence is 1 : 3100. While the novel AGL mutation c.1222C>T was not detectable among 198 German newborns, nine out of 272 children from the Faroese neonatal screening program were found to be heterozygous for this mutation. Thus, the calculated prevalence is 1 : 3600 (95% CI 1:700-1:6400). We conclude that due to a founder effect, the Faroe Islands have the highest prevalence of GSD IIIA world-wide. The detection of the molecular defect has facilitated the diagnosis and has offered the opportunity for prenatal diagnosis in this patient group.

Research paper thumbnail of Selenium as a potential protective factor against mercury developmental neurotoxicity

Environmental Research, 2008

Experimental studies suggest that selenium (Se) may decrease methylmercury (MeHg) toxicity under ... more Experimental studies suggest that selenium (Se) may decrease methylmercury (MeHg) toxicity under certain exposure regimens. In epidemiological studies, the exposure to MeHg occurs from fish and seafood, which are also a source of beneficial nutrients such as selenium. However, little is known about the potential protective effects of dietary Se against MeHg neurotoxicity in humans. The possible interaction was assessed in two birth cohorts in the Faroe Islands, consisting of singleton term births from 1986 to 1987 (N = 1,022), and 1994 to 1995 (N = 182), respectively. Dietary habits in this fishing population included frequent consumption of seafood, including whale meat high in mercury. Both Hg and Se were measured in cord whole blood. Neurodevelopmental outcomes were evaluated at age 7 years in both cohorts, and the smaller cohort also included neurological assessment on several prior occasions. Each outcome was modeled as a function of Hg and Se interactions (with adjustments for potential risk factors) by expressing the effects of log 10 (Hg) within the lowest 25%, the middle 50%, and the highest 25% of the Se distribution. Surplus Se was present in cord blood, the average being a 10-fold molar excess above MeHg. Regression analyses failed to show consistent effects of Se, or statistically significant interaction terms between Se and MeHg. Overall, no evidence was found that Se was an important protective factor against MeHg neurotoxicity. Prevention, therefore, needs to address MeHg exposures rather than Se intakes. Because of the benefits associated with fish intake during pregnancy, consumers should be advised to maintain a high fish and seafood intake that is low in Hg contamination. Additional research is needed to determine the identity of the nutrients responsible for the beneficial effects.

Research paper thumbnail of Allergy and Sensitization during Childhood Associated with Prenatal and Lactational Exposure to Marine Pollutants

Environmental Health Perspectives, 2010

Breast-feeding may affect the risk of developing allergy during childhood and may also cause expo... more Breast-feeding may affect the risk of developing allergy during childhood and may also cause exposure to immunotoxicants, such as polychlorinated biphenyls (PCBs), which are of concern as marine pollutants in the Faroe Islands and the Arctic region. The objective was to assess whether sensitization and development of allergic disease is associated with duration of breast-feeding and prenatal or postnatal exposures to PCBs and methylmercury. A cohort of 656 singleton births was formed in the Faroe Islands during 1999-2001. Duration of breast-feeding and history of asthma and atopic dermatitis were recorded at clinical examinations at 5 and 7 years of age. PCB and mercury concentrations were determined in blood samples obtained at parturition and at follow-up. Serum from 464 children (71%) at 7 years of age was analyzed for total immunoglobulin E (IgE) and grass-specific IgE. The total IgE concentration in serum at 7 years of age was positively associated both with the concomitant serum PCB concentration and with the duration of breast-feeding. However, the effect only of the latter was substantially attenuated in a multivariate analysis. A raised grass-specific IgE concentration compatible with sensitization was positively associated with the duration of breast-feeding and inversely associated with prenatal methylmercury exposure. However, a history of asthma or atopic dermatitis was not associated with the duration of breast-feeding, although children with atopic dermatitis had lower prenatal PCB exposures than did nonallergic children. These findings suggest that developmental exposure to immunotoxicants may both increase and decrease the risk of allergic disease and that associations between breast-feeding and subsequent allergic disease in children may, at least in part, reflect lactational exposure to immunotoxic food contaminants.

Research paper thumbnail of EDTA in Dried Blood Spots Leads to False Results in Neonatal Endocrinologic Screening

Clinical Chemistry, 2008

BACKGROUND: Blood samples for neonatal screening for inborn errors of metabolism are collected an... more BACKGROUND: Blood samples for neonatal screening for inborn errors of metabolism are collected and shipped on standardized filter paper cards. Occasionally these samples are contaminated with EDTA, which is often used for anticoagulation. EDTA may interfere with newborn screening tests based on lanthanide fluorescence and thus lead to false-negative or false-positive results.

Research paper thumbnail of Newborn screening for hepatorenal tyrosinemia by tandem mass spectrometry: analysis of succinylacetone extracted from dried blood spots

Clinical Biochemistry, 2004

Background: False-positive and false-negative results occur in current newborn-screening programs... more Background: False-positive and false-negative results occur in current newborn-screening programs for hepatorenal tyrosinemia, which measure tyrosine concentrations in blood spots, sometimes in combination with other metabolites, including succinylacetone. We present our experience with a newly described method for succinylacetone quantification in routine newborn screening. Methods: Succinylacetone was extracted from blood spots that had already been extracted with absolute methanol for acylcarnitine and amino acid analysis. The solvent was acetonitrile-water (80:20 by volume) containing formic acid, hydrazine hydrate, and 100 nmol/L 5,7-dioxooctanoic acid as internal standard. Analysis was performed by tandem mass spectrometry in a separate run. Results: Of 61 344 samples, 99.6% had succinylacetone concentrations <5 mol/L. With a cutoff of 10 mol/L, no false-positive results were obtained. In 2 patients, the succinylacetone concentrations in the dried blood spots from the 36th and 56th hours of life were 152 and 271 mol/L, respectively, and the tyrosine concentrations were 54 and 129 mol/L. Hepatorenal tyrosinemia was subsequently confirmed in both patients. Retrospective analysis of the neonatal screening samples of 2 addi-tional known patients revealed increased succinylacetone concentrations of 46 and 169 mol/L, respectively. Conclusions: Tandem mass spectrometric quantification directly from residual blood spots is a useful method for the early detection of hepatorenal tyrosinemia in newborn-screening programs.

Research paper thumbnail of Körpervorstellungen von Kindergartenkindern

Klinische Padiatrie, 1983

: Both from the view of the pediatrician (16) and the child analyst (3, 6, 9, 21), and recently, ... more : Both from the view of the pediatrician (16) and the child analyst (3, 6, 9, 21), and recently, too, by behavioral biologists (15) the emotional aspects of illness and hospitalization have been treated with increasing differentiation. On the other hand there are only few studies regarding the cognitive aspects of the problem, i.e. the concepts children have of their bodies and of illness, which depend on the momentary level of their intellectual development. Children's ideas and fears arising from illness or hospitalization frequently can only be understood with the knowledge of the actual body-image. Therefore we have tried to investigate by interviews and drawings of three- to seven-year-old preschoolers their conceptions of the interior of the body and its function. The sources of these ideas were discussed and some suggestions were made how the results of the study could be used in hospital and kindergarten.

Research paper thumbnail of EDTA in Dried Blood Spots Leads to False Results in Neonatal Endocrinologic Screening

BACKGROUND: Blood samples for neonatal screening for inborn errors of metabolism are collected an... more BACKGROUND: Blood samples for neonatal screening for inborn errors of metabolism are collected and shipped on standardized filter paper cards. Occasionally these samples are contaminated with EDTA, which is often used for anticoagulation. EDTA may interfere with newborn screening tests based on lanthanide fluorescence and thus lead to false-negative or false-positive results.

Research paper thumbnail of Asthma and allergy in children with and without prior measles, mumps, and rubella vaccination

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, Jan 3, 2015

The existing literature on the association between measles vaccination and subsequent risk of all... more The existing literature on the association between measles vaccination and subsequent risk of allergic disease is inconclusive. The aim of this study was, therefore, to determine whether measles, mumps and rubella (MMR) vaccination administered in early childhood was associated with asthma and allergic diseases at ages 5, 7 and 13 years in a birth cohort. In the Faroe Islands, 640 children were followed from birth. Follow-up examinations at ages 5, 7 and 13 years included a physical examination and a maternal questionnaire about the child's health. At age 7, total and grass-specific IgE was quantified in the child's serum, and at age 13, the children underwent skin prick tests (SPT). The child's vaccination card was reviewed at examinations. At age 5, 533 of 555 children had been vaccinated for MMR. After confounder adjustment we found early life MMR vaccination to be associated with a two-third reduction in the odds of asthma (OR: 0.33, 95% CI: 0.12; 0.90) and hypersens...

Research paper thumbnail of Application of a second-tier newborn screening assay for c5 isoforms

JIMD reports, 2014

We report a case of false-positive metabolic screening for isovaleric acidemia in a newborn due t... more We report a case of false-positive metabolic screening for isovaleric acidemia in a newborn due to treatment of the mother with pivalic acid containing antibiotics before delivery. By using a recently established second-tier test based on the tandem-MS technique, we could identify pivalic acid in a dried blood sample taken during routine neonatal screening. Before this second-tier test was initiated, diverse analytical procedures were performed in the baby to rule out isovaleric acidemia and carnitine supplementation was started. This caused additional psychological burden to the family. The direct use of the second-tier test would have avoided these negative consequences of a false-positive screening result.

Research paper thumbnail of Neonatal screening for citrullinaemia

European journal of pediatrics, 2003

In a period of 40 months (1st March 1999 to 30th June 2002) 610,000 blood samples were analysed i... more In a period of 40 months (1st March 1999 to 30th June 2002) 610,000 blood samples were analysed in one screening centre for citrulline as a pilot study for neonatal screening using tandem mass spectrometry. Persistent hypercitrullinaemia (Cit >1.5 mg/dl or 85.5 micro mol/l, not corrected for recovery) was identified in 15 newborns. Four children were diagnosed with classical neonatal onset citrullinaemia and eight with persisting asymptomatic hypercitrullinaemia. In two asymptomatic newborns and in one symptomatic preterm patient, argininosuccinate lyase deficiency was identified as the cause of moderately elevated levels of citrulline (cases not described in this paper). Citrulline concentrations were only temporarily mildly elevated in two newborns and in these the results of the original neonatal screening were therefore regarded as false-positive; we did not find any other false-positives. The screening result allowed the introduction of immediate specific treatment in two ca...

Research paper thumbnail of Tandemmassenspektrometrie

Monatsschrift Kinderheilkunde, 2000

Research paper thumbnail of Neurobehavioral performance of Inuit children with increased prenatal exposure to methylmercury

International Journal of Circumpolar Health, 2002

Exposure to methylmercury from marine mammals and other seafood may affect the development of the... more Exposure to methylmercury from marine mammals and other seafood may affect the development of the central nervous system. In a traditional Inuit community in Qaanaaq, Greenland, mercury concentrations in cord blood and maternal hair have been examined in connection with all births. We examined 43 children at age 7-12 years with a battery of neurobehavioral tests. The average mercury concentration in hair was 5.0 microg/g and 1.5 microg/g in children and mothers, respectively. Clinical neurological examination did not reveal any obvious deficits. However, neuropsychological tests showed possible exposure-associated deficits, though only in a few cases reaching statistical significance. In conjunction with data from other studies, peak latencies on brainstem auditory evoked potentials tended to be prolonged at increased exposure levels. The data from the present study therefore appears in accordance with other evidence that prenatal or early postnatal exposures to methylmercury may cause subtle neurobehavioral deficits.

Research paper thumbnail of Attenuated growth of breast-fed children exposed to increased concentrations of methylmercury and polychlorinated biphenyls

The FASEB Journal, 2003

Breast-feeding has been linked to slowed postnatal growth. Although the basis for this &amp;a... more Breast-feeding has been linked to slowed postnatal growth. Although the basis for this &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;weanling&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s dilemma&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; is unclear, environmental contaminants in human milk may be of relevance. We studied a Faroese birth cohort of 182 singleton children, born at term in 1994-95. Concentrations of mercury in cord blood and of polychlorinated biphenyls in maternal milk were measured, and duration of breast-feeding was recorded. At 18 months, children who had been exclusively breast-fed for at least 6 months weighed 0.59 kg less [95% confidence interval (CI) = 0.03, 1.16 kg] and were 1.50 cm [95% CI = 0.52, 2.47 cm] shorter than those not breast-fed. However, calculated transfer of contaminants from human milk fully explained the attenuated growth. Irrespective of duration of breast-feeding, a doubling of the mercury concentration in cord blood was associated with a decrease in weight at 18 months by 0.19 kg (95% CI = 0.03, 0.35 kg) and in height by 0.26 cm (95% CI = -0.02, 0.55 cm). Weight and height at 42 months showed the same tendencies, but the main effect occurred before 18 months of age. Thus, in communities with increased contaminant exposures, risks associated with lactational transfer of toxicants to the infant must be considered when judging the benefits of prolonged breast-feeding.

Research paper thumbnail of Rapid steroid hormone quantification for congenital adrenal hyperplasia (CAH) in dried blood spots using UPLC liquid chromatography–tandem mass spectrometry

Steroids, 2011

Newborn screening for congenital adrenal hyperplasia (CAH) is usually done by quantifying 17α-hyd... more Newborn screening for congenital adrenal hyperplasia (CAH) is usually done by quantifying 17α-hydroxyprogesterone using immunoassay. However, this test produces high rates of false positive results caused by cross reacting steroids. Therefore we have developed a selective and specific method with a short run time (1.25 min) for quantification of 17α-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, 11-deoxycorticosterone and cortisol from dried blood spots. The extraction procedure is very simple and steroid separation is ensured on a BEH C18 column and an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Analysis was done in positive ionization mode (ESI+) and recorded in multiple reaction monitoring mode (MRM). The method gave linear results for all steroids over a range of 5-200 (cortisol: 12.5-500)nmol/L with coefficients of regression &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.992. Absolute recovery was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;64.1%. Across the analytical range the inter-assay coefficient of variation (CV) was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;3%. Newborn blood samples of patients with confirmed 21-CAH and 11-CAH could clearly be distinguished from samples of unaffected newborns falsely positive on immunoassay. The method is not influenced by cross reactions as found on immunoassay. Analysis of dried blood spots shows that this method is sensitive and fast enough to allow rapid analysis and can therefore improve the newborn screening program.

Research paper thumbnail of Neonatal screening for defects of the mitochondrial trifunctional protein

Molecular Genetics and Metabolism, 2005

Long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deWciency has been included in the routine n... more Long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deWciency has been included in the routine neonatal screening program by the German screening commission. As tandem mass spectrometry (TMS) does not discriminate between the diVerent defects of the mitochondrial trifunctional protein (MTP) screening for isolated LCHAD deWciency includes the detection of long-chain 3-ketoacyl-CoA thiolase and complete MTP deWciencies as well. We identiWed 11 patients with abnormalities of the MTP out of 1.2 million newborns screened in our laboratory during the last 6 years. Treatment was started on the day the screening result was obtained (day 3 to day 9 of life). Seven of these newborns developed satisfactorily during an observation period of up to 64 months. They had isolated LCHAD deWciency, four of them caused by the typical mutation (1528 G>C), three others had no molecular genetic analysis done or were shown to have previously unknown mutations. Four children did not survive, two of them showing complete deWciency of MTP and two showing deWciency of long-chain 3-ketoacyl-CoA thiolase. We conclude that, despite the rarity of the disease, screening for MTP deWciencies is justiWed based on the following criteria: improved quality of life for patients with isolated LCHAD deWciency, absence of stigmatisation of babies showing mild variants without necessity of treatment, no signiWcant increase of the total number of false positive screening results, no false negative results to our knowledge. Finally, extension of analysis to MTP deWciencies is achieved without additional costs for screening laboratories already using TMS.  (J. Sander).

Research paper thumbnail of Dystonia and deafness due to SUCLA2 defect; Clinical course and biochemical markers in 16 children

Mitochondrion, 2009

Patients with SUCLA2 gene defects characteristically develop the trias of early hypotonia, progre... more Patients with SUCLA2 gene defects characteristically develop the trias of early hypotonia, progressive dystonia and sensori-neural deafness. We describe the clinical course and biochemical phenotype in 16 children from the Faroe Islands with a homozygous SUCLA2 splice site mutation. Elevated urinary 3-hydroxyisovaleric acid is a novel biochemical feature in patients. Progressive hearing loss, in combination with a characteristic metabolite profile (increased lactate, methylmalonic acid, C4-dicarboxylic carnitine, 3-hydroxyisovaleric acid) should lead the clinician to the correct diagnosis even in patients with only intermittent lactic acidemia. Direct SUCLA2 sequence analysis is suggested instead of an invasive muscle biopsy to obtain the diagnosis. Nutritional intervention may be considered in SUCLA2 patients.

Research paper thumbnail of Maternal seafood diet, methylmercury exposure, and neonatal neurologic function

The Journal of Pediatrics, 2000

Objective: To determine whether neonatal neurologic function is adversely affected b X seafood co... more Objective: To determine whether neonatal neurologic function is adversely affected b X seafood contaminants from maternal diet during pregnancy.

Research paper thumbnail of Birthweight in a fishing community: significance of essential fatty acids and marine food contaminants

International Journal of Epidemiology, 2001

Research paper thumbnail of Neonatal Screening: Identification of Children with 11ß-Hydroxylase Deficiency by Second-Tier Testing

Hormone Research in Paediatrics, 2012

21-Hydroxylase deficiency (21-OHD) is the target disease of newborn screening for congenital adre... more 21-Hydroxylase deficiency (21-OHD) is the target disease of newborn screening for congenital adrenal hyperplasia (CAH). We describe the additional detection of patients suffering from 11β-hydroxylase deficiency (11-OHD) by second-tier testing. Over a period of 5 years, screening for CAH was done in a total of 986,098 newborns by time-resolved immunoassay (DELFIA®) for 17α-hydroxyprogesterone (17-OHP). Positive samples were subsequently analyzed in an LC-MS/MS second-tier test including 17-OHP, cortisol, 11-deoxycortisol, 4-androstenedione and 21-deoxycortisol. In addition to 78 cases of 21-OHD, 5 patients with 11-OHD were identified. Diagnostic parameters were a markedly elevated concentration of 11-deoxycortisol in the presence of a low level of cortisol. Androstenedione was also increased. In contrast to 21-OHD, concentrations of 21-deoxycortisol were normal. Steroid profiling in newborn blood samples showing positive results in immunoassays for 17-OHP allows for differentiating 21-OHD from 11-OHD. This procedure may not detect all cases of 11-OHD in the newborn population because there may be samples of affected newborns with negative results for 17-OHP in the immunoassay.

Research paper thumbnail of Neonatal screening for medium chain acyl-CoA deficiency: high incidence in Lower Saxony (northern Germany)

European Journal of Pediatrics, 2001

Research paper thumbnail of Molecular genetic basis and prevalence of glycogen storage disease type IIIA in the Faroe Islands

European Journal of Human Genetics, 2001

Glycogen storage disease type IIIA (GSD IIIA) is caused by mutations of the amyloglucosidase gene... more Glycogen storage disease type IIIA (GSD IIIA) is caused by mutations of the amyloglucosidase gene (AGL). For most populations, none of the AGL mutations described to date is particularly frequent. In this paper, we report that six children with GSD IIIA from the Faroe Islands were found to be homozygous for the novel nonsense mutation c.1222C&gt;T (R408X) of the AGL gene. This mutation is easily detected by restriction enzyme digest with NsiI after mismatch PCR. Investigating five intragenic polymorphisms, we could show that this mutation was always associated with the same haplotype. The c.1222C&gt;T mutation could be detected on two chromosomes of another 50 unselected GSD IIIA patients of other European or North American origin which means that this mutation plays a minor role worldwide. From the fact that we are currently aware of a total of 14 GSD IIIA cases in the Faroese population of 45 000, the observed prevalence is 1 : 3100. While the novel AGL mutation c.1222C&gt;T was not detectable among 198 German newborns, nine out of 272 children from the Faroese neonatal screening program were found to be heterozygous for this mutation. Thus, the calculated prevalence is 1 : 3600 (95% CI 1:700-1:6400). We conclude that due to a founder effect, the Faroe Islands have the highest prevalence of GSD IIIA world-wide. The detection of the molecular defect has facilitated the diagnosis and has offered the opportunity for prenatal diagnosis in this patient group.

Research paper thumbnail of Selenium as a potential protective factor against mercury developmental neurotoxicity

Environmental Research, 2008

Experimental studies suggest that selenium (Se) may decrease methylmercury (MeHg) toxicity under ... more Experimental studies suggest that selenium (Se) may decrease methylmercury (MeHg) toxicity under certain exposure regimens. In epidemiological studies, the exposure to MeHg occurs from fish and seafood, which are also a source of beneficial nutrients such as selenium. However, little is known about the potential protective effects of dietary Se against MeHg neurotoxicity in humans. The possible interaction was assessed in two birth cohorts in the Faroe Islands, consisting of singleton term births from 1986 to 1987 (N = 1,022), and 1994 to 1995 (N = 182), respectively. Dietary habits in this fishing population included frequent consumption of seafood, including whale meat high in mercury. Both Hg and Se were measured in cord whole blood. Neurodevelopmental outcomes were evaluated at age 7 years in both cohorts, and the smaller cohort also included neurological assessment on several prior occasions. Each outcome was modeled as a function of Hg and Se interactions (with adjustments for potential risk factors) by expressing the effects of log 10 (Hg) within the lowest 25%, the middle 50%, and the highest 25% of the Se distribution. Surplus Se was present in cord blood, the average being a 10-fold molar excess above MeHg. Regression analyses failed to show consistent effects of Se, or statistically significant interaction terms between Se and MeHg. Overall, no evidence was found that Se was an important protective factor against MeHg neurotoxicity. Prevention, therefore, needs to address MeHg exposures rather than Se intakes. Because of the benefits associated with fish intake during pregnancy, consumers should be advised to maintain a high fish and seafood intake that is low in Hg contamination. Additional research is needed to determine the identity of the nutrients responsible for the beneficial effects.

Research paper thumbnail of Allergy and Sensitization during Childhood Associated with Prenatal and Lactational Exposure to Marine Pollutants

Environmental Health Perspectives, 2010

Breast-feeding may affect the risk of developing allergy during childhood and may also cause expo... more Breast-feeding may affect the risk of developing allergy during childhood and may also cause exposure to immunotoxicants, such as polychlorinated biphenyls (PCBs), which are of concern as marine pollutants in the Faroe Islands and the Arctic region. The objective was to assess whether sensitization and development of allergic disease is associated with duration of breast-feeding and prenatal or postnatal exposures to PCBs and methylmercury. A cohort of 656 singleton births was formed in the Faroe Islands during 1999-2001. Duration of breast-feeding and history of asthma and atopic dermatitis were recorded at clinical examinations at 5 and 7 years of age. PCB and mercury concentrations were determined in blood samples obtained at parturition and at follow-up. Serum from 464 children (71%) at 7 years of age was analyzed for total immunoglobulin E (IgE) and grass-specific IgE. The total IgE concentration in serum at 7 years of age was positively associated both with the concomitant serum PCB concentration and with the duration of breast-feeding. However, the effect only of the latter was substantially attenuated in a multivariate analysis. A raised grass-specific IgE concentration compatible with sensitization was positively associated with the duration of breast-feeding and inversely associated with prenatal methylmercury exposure. However, a history of asthma or atopic dermatitis was not associated with the duration of breast-feeding, although children with atopic dermatitis had lower prenatal PCB exposures than did nonallergic children. These findings suggest that developmental exposure to immunotoxicants may both increase and decrease the risk of allergic disease and that associations between breast-feeding and subsequent allergic disease in children may, at least in part, reflect lactational exposure to immunotoxic food contaminants.

Research paper thumbnail of EDTA in Dried Blood Spots Leads to False Results in Neonatal Endocrinologic Screening

Clinical Chemistry, 2008

BACKGROUND: Blood samples for neonatal screening for inborn errors of metabolism are collected an... more BACKGROUND: Blood samples for neonatal screening for inborn errors of metabolism are collected and shipped on standardized filter paper cards. Occasionally these samples are contaminated with EDTA, which is often used for anticoagulation. EDTA may interfere with newborn screening tests based on lanthanide fluorescence and thus lead to false-negative or false-positive results.

Research paper thumbnail of Newborn screening for hepatorenal tyrosinemia by tandem mass spectrometry: analysis of succinylacetone extracted from dried blood spots

Clinical Biochemistry, 2004

Background: False-positive and false-negative results occur in current newborn-screening programs... more Background: False-positive and false-negative results occur in current newborn-screening programs for hepatorenal tyrosinemia, which measure tyrosine concentrations in blood spots, sometimes in combination with other metabolites, including succinylacetone. We present our experience with a newly described method for succinylacetone quantification in routine newborn screening. Methods: Succinylacetone was extracted from blood spots that had already been extracted with absolute methanol for acylcarnitine and amino acid analysis. The solvent was acetonitrile-water (80:20 by volume) containing formic acid, hydrazine hydrate, and 100 nmol/L 5,7-dioxooctanoic acid as internal standard. Analysis was performed by tandem mass spectrometry in a separate run. Results: Of 61 344 samples, 99.6% had succinylacetone concentrations <5 mol/L. With a cutoff of 10 mol/L, no false-positive results were obtained. In 2 patients, the succinylacetone concentrations in the dried blood spots from the 36th and 56th hours of life were 152 and 271 mol/L, respectively, and the tyrosine concentrations were 54 and 129 mol/L. Hepatorenal tyrosinemia was subsequently confirmed in both patients. Retrospective analysis of the neonatal screening samples of 2 addi-tional known patients revealed increased succinylacetone concentrations of 46 and 169 mol/L, respectively. Conclusions: Tandem mass spectrometric quantification directly from residual blood spots is a useful method for the early detection of hepatorenal tyrosinemia in newborn-screening programs.