Maternal serum vitamin D level in early pregnancy and risk for preeclampsia: A case-control study in Southern Sweden.

BACKGROUND: Preeclampsia is considered a major cause of maternal and fetal morbidity and mortality. The aim of the present case-control study in Sweden was to assess the hypothesized association between low serum vitamin D concentrations in early pregnancy and the risk of developing preeclampsia since vitamin D may play a role in early placental development. METHODS: The study included 296 women diagnosed with preeclampsia (cases) and 580 healthy pregnant women (controls). Serum samples were obtained from a biobank of samples collected in early pregnancy including almost all pregnancies in Southern Sweden. Concentrations of 25-hydroxyvitamin D3 (vitamin D) were analyzed using liquid chromatography-tandem-mass-spectrometry (LC/MS/MS). The cases were divided into two categories: i) infants were born before gestational week 34 (early onset) and/or born small-for-gestational age (SGA)(n = 51), ii) and others defined as late onset (n = 245). Vitamin D concentrations were analyzed both as a continuous and a categorized variable. RESULTS: When all preeclampsia cases were included in the analyses no consistent patterns were observed. However, the median serum concentrations of vitamin D were significantly lower among the cases who were early onset and/or were born SGA (median 39.2 nmol/L, range 1.2-93.6) as compared to the controls (49.0 nmol/L, 0.1-219; p = 0.01). In addition, high concentrations were statistically significantly associated with a decreased risk of preeclampsia (>66.9 vs ≤30.1 nmol/L; crude OR 0.39, 95% CI 0.16-0.96). When potential confounders were included in the models the associations were even more pronounced. CONCLUSIONS: Our results support the hypothesis that vitamin D deficiency is a risk factor for preeclampsia, but only in preeclampsia cases who were early-onset and/or were born SGA. Preeclampsia is not a homogenous condition and more studies are needed before vitamin D supplementation during pregnancy can be recommended.

Hearing loss in patients with mucopolysaccharidosis II: data from HOS - the Hunter Outcome Survey.

BACKGROUND: Subjectively reported hearing loss is a common feature of mucopolysaccharidosis II (MPS II, Hunter syndrome). This study provides an epidemiological description of hearing loss and other otolaryngological manifestations reported by patients registered in the Hunter Outcome Survey (HOS), an international registry of patients with MPS II. METHODS: Data about ear signs and symptoms were available for 554 of the 605 patients alive at HOS entry. The degree of hearing loss for 162 pure-tone audiograms (PTAs) from 83 patients was classified by independent interpreters using both the age-specific International Institute of Standardization (ISO) 7029 standard and the age-independent World Health Organization (WHO) clinical guidelines. A linear regression analysis using cross-sectional data was conducted to investigate the relationship between hearing loss and age. RESULTS: The most prevalent otolaryngological manifestations and interventions reported were otitis (either acute otitis media or chronic otitis media [72%]), hearing loss (67%), insertion of ventilation tubes (50%), adenoidectomy (47%), and hearing aids (41%). According to the ISO standard, only one patient out of the 83 with audiogram data in HOS had normal hearing in both ears at all time points. According to the WHO classification, 16% had normal hearing; hearing loss was mild in 24%, moderate in 31%, severe in 22%, and profound in 7%. In the linear regression analysis, the hearing threshold in the cohort increased with age at an estimated rate of approximately 1 dB per year. CONCLUSIONS: Hearing impairment is common in MPS II. Early otolaryngological evaluation and intervention is recommended.

MtDNA mutations are a common cause of severe disease phenotypes in children with Leigh syndrome.

Leigh syndrome is a common clinical manifestation in children with mitochondrial disease and other types of inborn errors of metabolism. We characterised clinical symptoms, prognosis, respiratory chain function and performed extensive genetic analysis of 25 Swedish children suffering from Leigh syndrome with the aim to obtain insights into the molecular pathophysiology and to provide a rationale for genetic counselling. We reviewed the clinical history of all patients and used muscle biopsies in order to perform molecular, biochemical and genetic investigations, including sequencing the entire mitochondrial DNA (mtDNA), the mitochondrial DNA polymerase (POLGA) gene and the surfeit locus protein 1 (SURF1) gene. Respiratory chain enzyme activity measurements identified five patients with isolated complex I deficiency and five with combined enzyme deficiencies. No patient presented with isolated complex IV deficiency. Seven patients had a decreased ATP production rate. Extensive sequence analysis identified eight patients with pathogenic mtDNA mutations and one patient with mutations in POLGA. Mutations of mtDNA are a common cause of LS and mtDNA analysis should always be included in the diagnosis of LS patients, whereas SURF1 mutations are not a common cause of LS in Sweden. Unexpectedly, age of onset, clinical symptoms and prognosis did not reveal any clear differences in LS patients with mtDNA or nuclear DNA mutations.

Prenatal treatment for serious neurological sequelae of congenital toxoplasmosis: an observational prospective cohort study.

BACKGROUND: The effectiveness of prenatal treatment to prevent serious neurological sequelae (SNSD) of congenital toxoplasmosis is not known. METHODS AND FINDINGS: Congenital toxoplasmosis was prospectively identified by universal prenatal or neonatal screening in 14 European centres and children were followed for a median of 4 years. We evaluated determinants of postnatal death or SNSD defined by one or more of functional neurological abnormalities, severe bilateral visual impairment, or pregnancy termination for confirmed congenital toxoplasmosis. Two-thirds of the cohort received prenatal treatment (189/293; 65%). 23/293 (8%) fetuses developed SNSD of which nine were pregnancy terminations. Prenatal treatment reduced the risk of SNSD. The odds ratio for prenatal treatment, adjusted for gestational age at maternal seroconversion, was 0.24 (95% Bayesian credible intervals 0.07-0.71). This effect was robust to most sensitivity analyses. The number of infected fetuses needed to be treated to prevent one case of SNSD was three (95% Bayesian credible intervals 2-15) after maternal seroconversion at 10 weeks, and 18 (9-75) at 30 weeks of gestation. Pyrimethamine-sulphonamide treatment did not reduce SNSD compared with spiramycin alone (adjusted odds ratio 0.78, 0.21-2.95). The proportion of live-born infants with intracranial lesions detected postnatally who developed SNSD was 31.0% (17.0%-38.1%). CONCLUSION: The finding that prenatal treatment reduced the risk of SNSD in infected fetuses should be interpreted with caution because of the low number of SNSD cases and uncertainty about the timing of maternal seroconversion. As these are observational data, policy decisions about screening require further evidence from a randomized trial of prenatal screening and from cost-effectiveness analyses that take into account the incidence and prevalence of maternal infection. Please see later in the article for the Editors' Summary.

Importance of surgical history in diagnosing mucopolysaccharidosis type II (Hunter syndrome): data from the Hunter Outcome Survey.

PURPOSE: To characterize surgical histories typical of patients with mucopolysaccharidosis type II, thereby broadening understanding of the natural history of these patients and helping physicians recognize the disease. METHODS: Data on surgical interventions from the Hunter Outcome Survey--a multinational, observational database of patients with mucopolysaccharidosis type II-were analyzed. The study population comprised 527 patients for whom surgical data were reported on/before July 23, 2009. RESULTS: Surgical interventions were performed in 83.7% of the study population. Patients underwent their first operation at a median age of 2.6 years. Tympanostomies, repairs of inguinal hernias, and operations for carpal tunnel syndrome were performed in a greater proportion of the study population than the general population. A median of 3.0 operations was performed per patient; repeat operations for hernia or carpal tunnel syndrome were common. The majority of patients (221/389) underwent at least one surgical intervention before diagnosis of mucopolysaccharidosis type II. CONCLUSION: Patients with mucopolysaccharidosis type II typically undergo surgical intervention at a young age, often before diagnosis. Repeated early surgical interventions, particularly for hernias or carpal tunnel syndrome, are characteristic of patients with mucopolysaccharidosis type II. We recommend that such patients are carefully examined for manifestations of mucopolysaccharidosis disorders and referred for diagnostic testing.

[Treatment of erectile dysfunction - from pill to implant]. / Behandling av erektil dysfunktion ­ från piller till implantat - Region Skåne har kapat kön till implantatkirurgi utan att urologisk cancerkirurgi påverkats.

The article gives an overview of erectile mechanisms and erectile dysfunction (ED). Current treatment of ED is presented. Most of the patients with ED should be treated by their primary care physician. Urologists should be involved only when treatment has failed, and when erectile implants might be an option. In Skåne the waiting list for these patients has been eliminated by using the operating capacity of a smaller hospital.

High prevalence of cardio-metabolic risk factors among adolescents with intellectual disability.

UNLABELLED: Adults with intellectual disabilities (IDs) have poor lifestyle-related health compared with the general population. Our aim was to study whether such differences are present already in adolescents. AIM: To compare the prevalence and severity of cardio-metabolic risk factors and cardio-vascular fitness in adolescents with and without IDs. METHODS: Intellectual disability (ID) students (n = 66) and non-intellectual disability (non-ID) students from practical (non-ID-p) (n = 34) and theoretical (non-ID-t) (n = 56) programmes were recruited from three upper secondary schools. Anthropometric data, blood pressure, body composition, fasting-insulin, fasting-glucose, fasting-lipids and cardio-vascular fitness were measured. RESULTS: Participants with and without ID differed significantly in the prevalence of cardio-metabolic risk factors with participants with ID having a higher percentage of total fat mass, wider waist circumferences (WCs), lower levels of fat-free mass (FFM), lower bone mineral density (BMD) and higher insulin and homeostasis model assessment of insulin resistance (HOMA) levels and poorer cardio-vascular fitness. The healthiest levels were found in the non-ID-t group compared to the group with ID and the group with non-ID-p in between. CONCLUSION: The prevalence of cardio-metabolic risk factors and poor cardio-vascular fitness was found to be high in this young population with intellectual disabilities. Measures should be taken to improve the health messages directed towards children and adolescents with intellectual disabilities.

Neuropsychologic outcomes in children with neonatal herpes encephalitis.

Neonatal herpes simplex virus infection with involvement of the central nervous system is a serious disease with high morbidity, even with acyclovir therapy. The disability includes cerebral palsy and different aspects of cognitive dysfunction which are of utmost importance for the child's future habilitation. We conducted a descriptive cohort study to define neuropsychologic outcomes and determine the relationship between neonatal neuroimaging and neuropsychologic outcomes. Among 267,690 children born in the Stockholm area over 12 years (1989-2000), 14 were diagnosed with neonatal herpes including central nervous system involvement. Nine children were neuropsychologically evaluated. Neonatal herpes virus infection had an even greater impact on cognitive function, speech ability, and attention deficit than anticipated. Relapse leading to deterioration was demonstrated in one child. Social skills were influenced to a lesser degree. Neurodevelopmental outcomes of the children were not well-correlated with extent of cerebral damage as visualized by computed tomography at 7-28 days after onset of signs. Neuropsychologic assessment is essential in the habilitation of the child, and a prerequisite for the evaluation of new treatments and for the assessment of deterioration of cerebral function related to relapses.

Mucopolysaccharidoses in the Scandinavian countries: incidence and prevalence.

AIM: The aim of this study was to estimate the incidence and prevalence of mucopolysaccharidoses (MPS disorders) in Scandinavia. METHODS: The retrospective period used for the incidence study covered the period from 1975 to 2004 in Sweden and Denmark and from 1979 to 2004 in Norway. Prevalence was derived from the number of MPS patients alive as of December 31, 2007. RESULTS: The incidence of all MPS disorders was 1.75 cases in Sweden, 3.08 cases in Norway and 1.77 cases in Denmark per 100 000 newborns. The incidence of MPS I was the most common in all three countries, with 0.67, 1.85 and 0.54 cases per 100 000 newborns, respectively; for MPS II, numbers were 0.27, 0.13 and 0.27, respectively. For patients with other MPS disorders the incidence varied widely. The prevalence for all MPS disorders was 4.24, 7.06 and 6.03 per 1 000 000 inhabitants in Sweden, Norway and Denmark, respectively. CONCLUSION: From three Scandinavian countries the incidence of MPS disorders is retrospectively evaluated for 25 years in Norway and 30 years in Sweden and Denmark. Incidence and prevalence studies of lysosomal disorders are prerequisites for cost benefit calculations in the face of newly developed and expensive therapies in the future.

Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients.

Cornelia de Lange syndrome (CdLS; OMIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by distinctive dysmorphic facial features, severe growth and developmental delay and abnormalities of the upper limbs. About 50% of CdLS patients have been found to have heterozygous mutations in the NIPBL gene and a few cases were recently found to be caused by mutations in the X-linked SMC1L1 gene. We performed a mutation screening of all NIPBL coding exons by direct sequencing in 11 patients (nine sporadic and two familial cases) diagnosed with CdLS in Sweden and detected mutations in seven of the cases. All were de novo, and six of the mutations have not been previously described. Four patients without identifiable NIPBL mutations were subsequently subjected to multiplex ligation-dependent probe amplification analysis to exclude whole exon deletions/duplications of NIPBL. In addition, mutation analysis of the 5' untranslated region (5' UTR) of NIPBL was performed. Tiling resolution array comparative genomic hybridization analysis was carried out on these four patients to detect cryptic chromosome imbalances and in addition the boys were screened for SMC1L1 mutations. We found a de novo 9p duplication with a size of 0.6 Mb in one of the patients with a CdLS-like phenotype but no mutations were detected in SMC1L1. So far, two genes (NIPBL and SMC1L1) have been identified causing CdLS or CdLS-like phenotypes. However, in a considerable proportion of individuals demonstrating the CdLS phenotype, mutations in any of these two genes are not found and other potential loci harboring additional CdLS-causing genes should be considered.

Congenital cytomegalovirus infections.

Congenital cytomegalovirus (CMV) infection is one of the most common viral causes of congenital infections in high resource countries and a leading cause of hearing loss as well as an important contributor to neurodevelopmental disabilities in children. During early pregnancy, CMV has a teratogenic potential and may cause malformations such as migrational disturbances in the brain, which can be visualised using neuroimaging methods such as magnetic resonance imaging (MRI) in such children. As a consequence of variation in epidemiology and seropositivity in fertile women, the prevalence of congenital CMV in their offspring varies in different countries between 0.15-2.0%. Some 10-20% of all children with congenital CMV infections exhibit signs of neurological damage when followed up. This is the case in children both with and without symptoms of infection at birth. Until vaccines and non-toxic antiviral agents are available, hygienic measures are important as prophylaxis. Treatment with antiviral agents may have a place in children with central nervous system involvement during the neonatal period.

Seasonal fluctuation in the secretion of the antioxidant melatonin is not associated with alterations in sperm DNA damage.

A high sperm DNA fragmentation index (DFI) is associated with reduced fertility. DFI is influenced by the balance between reactive oxygen species and antioxidants. A circannual variation in melatonin, an antioxidant and free radical scavenger, could thus impact semen quality and fertility. The association between the major melatonin metabolite, urine 6-sulfatoxymelatonin (aMT6s), and DFI was analyzed in 110 Oslo men (south of the Arctic Circle) and 86 Tromsoe men (north of the Arctic Circle). Two semen analyses, summer and winter, and four urine samples (early/late summer; early/late winter), were analyzed. The associations between aMT6s in urine and DFI were characterized in a cross-sectional and longitudinal manner using correlation analysis and linear regression. Regardless of season and location, no significant correlations between aMT6s and DFI were observed. The correlation coefficients for associations between changes over time (early winter-early summer) in aMT6s and DFI were for the total cohort: rho = -0.08 (P = 0.322), for the Oslo cohort: rho = -0.07 (P = 0.485), and for the Tromsoe cohort: rho = -0.14 (P = 0.273), respectively. Similar results were seen when comparing late winter and late summer. There was no any statistically significant correlation between changes over time in aMT6s and DFI for men with DFI below and above the median value (10%), respectively. The seasonal variation in melatonin excretion seems not to have any impact on DFI.

Allogeneic hematopoietic stem cell transplantation for inherited disorders: experience in a single center.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (ASCT) is a possible cure for many inherited disorders. METHODS: We report 20 years of experience in 71 patients. The disorders include 7 immunodeficiencies, 21 hematological disorders, 13 histiocytic disorders, 9 mucopolysaccharoidoses, 7 metachromatic leukodystrophies (MLD), 3 adrenoleukodystrophies (ALD), 2 adrenomyeloneuropathy (AMN), 6 patients with Gaucher's disease, 1 Sandhoff's disease, and 2 patients with aspartylglucosaminuria. Their median age was 4 (0-39) years. The donors were 29 HLA-identical related, 27 matched unrelated (MUD) and 15 HLA mismatches. RESULTS: In recipients of HLA-identical sibling grafts, none developed acute GVHD grades II-IV as against 22% in all others. The overall cumulative incidence of chronic GVHD was 17%. The 5-year survival rates were 93%, 84%, and 46% in recipients of grafts from HLA-identical siblings, MUD and HLA-mismatches, respectively. The overall 10-year survival rate was 69%. All of the surviving patients with immunodeficiencies and hemoglobinopathies are well. Four patients with Hurler's disease are also well, apart from skeletal problems. Five patients with Gaucher's disease are between 14 and 22 years after the transplant. Two infants with MLD deteriorated, a girl with the juvenile form has stable disease and one woman with the adult form has improved. Among four survivors with ALD/AMN, three are well and one has dementia. Two patients with aspartylglucosaminuria have stable disease. CONCLUSION: In patients with inborn errors of metabolism, ASCT gives a high survival rate using HLA-matched donors. Beneficial effects are seen in those who are transplanted early.

Association between congenital toxoplasmosis and parent-reported developmental outcomes, concerns, and impairments, in 3 year old children.

BACKGROUND: Information is lacking on the effects of congenital toxoplasmosis on development, behavior, and impairment in later childhood, as well as on parental concerns and anxiety. This information is important for counselling parents about the prognosis for an infected child and for policy decisions on screening. METHODS: We prospectively studied a cohort of children identified by screening for toxoplasmosis in pregnant women or neonates between 1996 and 2000 in ten European centers. At 3 years of age, parents of children with and without congenital toxoplasmosis were surveyed about their child's development, behavior, and impairment, and about parental concerns and anxiety, using a postal questionnaire. RESULTS: Parents of 178/223 (80%) infected, and 527/821 (64%) uninfected children responded. We found no evidence that impaired development or behavior were more common in infected children, or that any potential effect of congenital toxoplasmosis was masked by prenatal treatment. Parents of infected children were significantly more anxious and reported more visual problems in their children. CONCLUSION: On average, children aged three to four years with congenital toxoplasmosis identified by screening and treated during infancy in this European setting had risks of abnormal development and behavior similar to uninfected children. Parental anxiety about infected children needs to be addressed by clinicians. Future studies with longer follow up and clinician-administered assessments may be better able to detect any subtle differences in child outcomes.

Reproductive function during summer and winter in Norwegian men living north and south of the Arctic circle.

Seasonal, daylight-dependent variation in human spermatozoa counts, with lowest values during summer, has been suggested. To test this hypothesis, we performed a longitudinal study of semen quality and reproductive hormone levels in Norwegian men living north and south of the Arctic Circle. An ejaculate and a serum specimen were obtained both in summer and in winter from 92 volunteers in Tromsoe (69 degrees north latitude) and 112 in Oslo (60 degrees north latitude). Semen analyses were performed, and serum was assayed for FSH and inhibin B. The median spermatozoa concentration in Tromsoe after adjustment for abstinence period length was 49 x 10(6)/ml in summer and 54 x 10(6)/ml in winter. Corresponding values for Oslo were 59 x 10(6)/ml and 54 x 10(6)/ml. The seasonal differences in spermatozoa concentration were not statistically significant, nor were significant differences observed in median total spermatozoa count, semen volume, percentage progressive motile spermatozoa, or FSH. In Tromsoe, but not Oslo, inhibin B concentration was slightly, but significantly (P = 0.02) higher in winter than summer (229 ng/liter vs. 223 ng/liter). The length of the daylight period may have a slight impact on hormonal markers of spermatogenesis but does not cause substantial changes in spermatozoa numbers and motility.

Five-year follow-up of two siblings with aspartylglucosaminuria undergoing allogeneic stem-cell transplantation from unrelated donors.

BACKGROUND: Aspartylglucosaminuria is a rare, inherited lysosomal disease characterized by a slowly progressive mental retardation and coarse facial and body features. With the intent to provide the deficient enzyme aspartylglucosaminidase, allogeneic stem-cell transplantation (ASCT) has been attempted. Only a few cases of transplants have been reported. METHODS: Two siblings with aspartylglucosaminuria underwent allogeneic bone marrow transplants using unrelated human leukocyte antigen-A, -B, and DR identical donors at ages 10 years 5 months and 5 years 10 months, respectively. They were followed during 5 years with biochemical, neuroradiologic, neuropsychologic, and clinical investigations. RESULTS: During 5 years follow-up, no neuropsychologic or clinical deterioration was noted in the children. A stable expression of aspartylglucosaminidase was found during the whole follow-up period. The spinal fluid concentration of Tau-protein, a marker of neuronal and axonal degeneration and damage, peaked at approximately 12 months after bone-marrow transplantation and then declined to almost normal levels after 5 years. By magnetic resonance imaging (MRI), an improvement of myelination in the youngest sibling and an arrest of demyelination in the older one were observed. CONCLUSION: The importance of long-term follow-up of children after ASCT in this rare, very slowly progressive lysosomal disease must be emphasized. We report that none of the children had lost any capabilities since the transplantation; moreover, an improvement is shown in biochemical markers and MRI white-matter signals, suggesting a beneficial effect.

Detection of herpes simplex virus DNA in dried blood spots making a retrospective diagnosis possible.

BACKGROUND: Herpes simplex virus (HSV) infections in neonates are associated with life-threatening disease. Early diagnosis and treatment with antiviral therapy has decreased the morbidity, mortality and long-term sequelae in surviving children. The aim of the study was to investigate if herpes simplex virus DNA detection in dried blood spots on filter papers (Guthrie cards) sampled for screening of metabolic diseases may contribute to early diagnosis of neonatal HSV infection and enable pre-emptive therapy. METHODS: For detection of HSV-1 and -2 DNA, two different DNA extraction methods were evaluated. A minimal essential medium (MEM) extraction method was found superior and was used in combination with detection of HSV-1 and -2 DNA by PCR in dried blood spots from children with verified neonatal HSV infection. Cards from 28 children were included. The onset of illness varied from day 0 to 42 days and was the result of different types of maternal infection (27 cases) and an external source (one case). RESULTS: HSV DNA was detected in seven of the 28 Guthrie cards, two were HSV-1 and five were HSV-2 DNA positive. Positive dried blood spot cards were sampled within the interval 5 days before, to 6 days after onset of neonatal herpes. In cases of late onset CNS disease, viremia, was not demonstrable at the age of 3-5 days, the time period when the blood spot cards are normally sampled. CONCLUSION: Viremia, the prerequisite for demonstrating HSV DNA in dried blood spot cards preceded the onset of illness by up to 5 days and lasted at least up to 6 days thereafter. Analysis of HSV DNA in dried blood spot cards may be of value in the diagnostic arsenal for early onset of neonatal herpes and also have a role in the follow up of a child exposed at delivery. As the majority of the later onset neonatal herpes encephalitis cases are missed, a large-scale neonatal screening does not seem appropriate.

[Mucopolysaccharidoses. New therapeutic possibilities increase the need of early diagnosis]. / Mukopolysackaridossjukdomarna. Nya möjliga behandlingsmetoder ökar kraven på tidig diagnostik.

The mucopolysaccharide (MPS) diseases are a group of inherited, progressive, lysosomal disorders due to deficiencies in various enzymes involved in the lysosomal degradation of cellular glycosaminoglycans (GAG). The six MPS-diseases share clinical features, but each has unique characteristics as well. There is a wide variation in clinical symptomatology even within the same enzyme deficiency. The MPS-diseases are very rare, with only 1-2 affected children born yearly in Sweden (100.000 births). Prenatal diagnosis is available for each condition. Bone-marrow transplantation has been utilized to replace the enzyme deficiency in Hurler's syndrome (MPS I) and Maroteaux-Lamy's syndrome (MPS VI) for the past two decades. When performed before 18-24 months of age in Hurler's syndrome, mental development can be preserved. In this overview we present Swedish incidence and prevalence figures for the different forms of mucopolysaccharidosis, typical symptoms at onset, complications, diagnostic methods and a summary of the present status of research, and finally options for future treatment.

Differences in serum levels of CB-153 and p,p'-DDE, and reproductive parameters between men living south and north in Norway.

Arctic is contaminated with persistent organochlorine pollutants (POPs), and exposure to these compounds may differ between south and north in Norway. POPs may have negative impact on male reproductive characteristics. We compared serum levels of the CB-153 and p,p'-DDE in men who were born and had lived most of their lifetime south and north (close to or above the Arctic Circle) in Norway. We found no geographical differences in levels of CB-153 (south: 50 ng/g lipid (mean), north: 59 ng/g lipid; p=0.27) or sperm parameters. However, the levels of p,p'-DDE were higher in south than in north (81 ng/g lipid (mean) vs. 66 ng/g lipid; p=0.02), as were the levels of total and free testosterone. The FSH levels were lowest in south. A strong relationship between the CB-153 and the SHBG levels was observed. The regional differences observed for p,p'-DDE, testosterone and FSH were not reflected in the semen quality.