Maternal obesity, interpregnancy weight changes and congenital heart defects in the offspring: a nationwide cohort study.

OBJECTIVE: To evaluate the association between maternal BMI and congenital heart defects (CHDs) in the offspring when including live births, stillbirths, aborted and terminated pregnancies and to investigate if maternal interpregnancy weight changes between the first and second pregnancy influences the risk of foetal CHDs. METHODS: A nationwide cohort study of all singleton pregnancies in Denmark from 2008 to 2018. Data were retrieved from the Danish Foetal Medicine Database, which included both pre- and postnatal diagnoses of CHDs. Children or foetuses with chromosomal aberrations were excluded. Odds ratios were calculated with logistic regression models for CHDs overall, severe CHDs and five of the most prevalent subtypes of CHDs. RESULTS: Of the 547 105 pregnancies included in the cohort, 5 442 had CHDs (1.0%). Risk of CHDs became gradually higher with higher maternal BMI; for BMI 25-29.9 kg/m2, adjusted odds ratio (aOR) 1.17 (95% CI 1.10-1.26), for BMI 30-34.9 kg/m2, aOR 1.21 (95% CI 1.09-1.33), for BMI 35-39.9 kg/m2, aOR 1.29 (95% CI 1.11-1.50) and for BMI ≥ 40 kg/m2, aOR 1.85 (95% CI 1.54-2.21). Data was adjusted for maternal age, smoking status and year of estimated due date. The same pattern was seen for the subgroup of severe CHDs. Among the atrioventricular septal defects (n = 231), an association with maternal BMI ≥ 30 kg/m2 was seen, OR 1.67 (95% CI 1.13-2.44). 109 654 women were identified with their first and second pregnancies in the cohort. Interpregnancy BMI change was associated with the risk of CHDs in the second pregnancy (BMI 2 to < 4 kg/m2: aOR 1.29, 95% CI 1.09-1.53; BMI ≥ 4 kg/m2: aOR 1.36, 95% CI 1.08-1.68). CONCLUSION: The risk of foetal CHDs became gradually higher with higher maternal BMI and interpregnancy weight increases above 2 BMI units were also associated with a higher risk of CHDs.

Effects of escitalopram on synaptic density in the healthy human brain: a randomized controlled trial.

Selective serotonin reuptake inhibitors (SSRIs) are widely used for treating neuropsychiatric disorders. However, the exact mechanism of action and why effects can take several weeks to manifest is not clear. The hypothesis of neuroplasticity is supported by preclinical studies, but the evidence in humans is limited. Here, we investigate the effects of the SSRI escitalopram on presynaptic density as a proxy for synaptic plasticity. In a double-blind placebo-controlled study (NCT04239339), 32 healthy participants with no history of psychiatric or cognitive disorders were randomized to receive daily oral dosing of either 20 mg escitalopram (n = 17) or a placebo (n = 15). After an intervention period of 3-5 weeks, participants underwent a [11C]UCB-J PET scan (29 with full arterial input function) to quantify synaptic vesicle glycoprotein 2A (SV2A) density in the hippocampus and the neocortex. Whereas we find no statistically significant group difference in SV2A binding after an average of 29 (range: 24-38) days of intervention, our secondary analyses show a time-dependent effect of escitalopram on cerebral SV2A binding with positive associations between [11C]UCB-J binding and duration of escitalopram intervention. Our findings suggest that brain synaptic plasticity evolves over 3-5 weeks in healthy humans following daily intake of escitalopram. This is the first in vivo evidence to support the hypothesis of neuroplasticity as a mechanism of action for SSRIs in humans and it offers a plausible biological explanation for the delayed treatment response commonly observed in patients treated with SSRIs. While replication is warranted, these results have important implications for the design of future clinical studies investigating the neurobiological effects of SSRIs.

The Role of Leptin in Fetal Growth during Pre-Eclampsia.

Leptin is secreted by the placenta and has a multi-facetted role in the regulation of functions related to pregnancy. Metabolic disorders and insufficient homeostatic compensatory mechanisms involving leptin during pregnancy play a decisive role in the development of pre-eclampsia (PE) and give rise to compromised intrauterine growth conditions and aberrant birth weight of offspring. This review was compiled to elucidate the metabolic background of PE and its relationship with adverse intrauterine growth conditions through the examination of leptin as well as to describe possible mechanisms linking leptin to fetal growth restriction. This review illustrates that leptin in PE is dysregulated in maternal, fetal, and placental compartments. There is no single set of unifying mechanisms within the spectrum of PE, and regulatory mechanisms involving leptin are specific to each situation. We conclude that dysregulated leptin is involved in fetal growth at many levels through complex interactions with parallel pregnancy systems and probably throughout the entirety of pregnancy.

Ultimately, What is Forest Landscape Restoration in Practice? Embodiments in Sub-Saharan Africa and Implications for Future Design.

Forest landscape restoration (FLR) is gaining ground as a novel, holistic approach to sustainable environmental management across developing countries. In sub-Saharan Africa, 30 countries have joined the African Forest Landscape Restoration Initiative to advance FLR goals. Although conceptually compelling, and despite efforts articulating initial implementation guidelines, divergent discourses and interpretations confound FLR translation into practice. We propose a characterization of FLR in practice using insights from political ecology; principles of ecological restoration and landscape sustainability science; and the philosophy, principles, and objectives of the FLR paradigm. Our qualitative analysis further draws on secondary data and insights from participant observation during FLR-related workshops. We build and organize the FLR characterization around answers to ten questions: why restoration; what purpose; for what desired outcomes; where (location and land uses); what spatial extent and scale(s); who; which techniques; how (approach/strategy); when and how long; and how much to achieve. We then assess early FLR strategic priorities for interventions across nine African countries and analyze five selected actual projects to illustrate use of the proposed FLR characterization framework. The illustrative characterization of both planned interventions and actual projects does not reflect all the proposed characteristics of FLR in practice. Missing features include the initial biophysical condition, the desired target ecosystem state, and evaluation dimensions, and ill-articulated aspects include cross-sectoral integrations. We contend that any significant differences between FLR conceptualization, including its principles, and the practical manifestations can undermine coherence, the value that the FLR approach adds, and its wider adoption. The proposed characterization of FLR in practice contributes to scholarly attempts to realign FLR conceptual philosophy, principles, and rhetoric to its practical manifestations in different contexts, and can inform future design of FLR undertakings for more inclusive landscape governance.

Improved radiosynthesis and preliminary in vivo evaluation of the 11C-labeled tetrazine [11C]AE-1 for pretargeted PET imaging.

Pretargeted nuclear imaging based on the ligation between tetrazines and nano-sized targeting agents functionalized with trans-cyclooctene (TCO) has recently been shown to improve both imaging contrast and dosimetry in nuclear imaging of nanomedicines. Herein, we describe the improved radiosynthesis of a 11C-labeled tetrazine ([11C]AE-1) and its preliminary evaluation in both mice and pigs. Pretargeted imaging in mice was carried out using both a new TCO-functionalized polyglutamic acid and a previously reported TCO-functionalized bisphosphonate system as targeting agents. Unfortunately, pretargeted imaging was not successful using these targeting agents in pair with [11C]AE-1. However, brain imaging in pig indicated that the tracer crossed the blood-brain-barrier. Hence, we suggest that this tetrazine scaffold could be used as a starting point for the development of pretargeted brain imaging, which has so far been a challenging task.

Exploring Perceptions of Continuity of Care Among People With Long-Term Mental Disorders in Denmark.

Continuity of mental health care is central to improve the treatment and rehabilitation of people with mental disorders. While most studies on continuity of care fail to take the perspectives of service users into account, the aim of this study was to explore the perceived meanings of continuity of care among people with long-term mental disorders. Fifteen service users participated in semi-structured in-depth interviews. We used template analysis to guide the analysis. The main transversal themes of continuity were "Navigating the system" and "Connecting to people and everyday life." While the first theme related to the participants' experiences of their interaction with the mental health care system, the latter related to their hopes and perceived opportunities for a good life as desired outcomes of mental health care. We conclude that efforts to improve continuity of mental health care should be tailored to the priorities of service users.

Association between levels of persistent organic pollutants in adipose tissue and cryptorchidism in early childhood: a case-control study.

BACKGROUND: Congenital cryptorchidism, i.e. failure of the testicular descent to the bottom of the scrotum, is a common birth defect. The evidence from epidemiological, wildlife, and animal studies suggests that exposure to mixtures of endocrine disrupting chemicals during fetal development may play a role in its pathogenesis. We aimed to assess the association between cryptorchidism and prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), and polybrominated diphenyl ethers (PBDEs). METHODS: We conducted a case-control study consisting of 44 cryptorchid cases, and 38 controls operated for inguinal hernia, umbilical hernia, or hydrocele at the Turku University Hospital or Rigshospitalet, Copenhagen in 2002-2006. During the operation a subcutaneous adipose tissue biopsy was taken. Samples were analysed for 37 PCBs, 17 PCDD/Fs and 14 PBDEs by gas chromatography-high-resolution mass spectrometry. Chemical concentrations were adjusted for postnatal variation introduced by differences in duration of breastfeeding, age at the operation, and country of origin with a multiple linear regression. Association between adjusted and unadjusted chemical concentrations and the risk of cryptorchidism were analysed with logistic regression to get an estimate for odds ratio (OR) of cryptorchidism per multiplication of chemical concentrations with ca. 2.71 (Napier's constant). RESULTS: Total-TEq i.e. the WHO-recommended 2,3,7,8-TCDD equivalent quantity of 17 dioxins and 12 dioxin-like PCBs and sum of PCDD/Fs were positively associated with cryptorchidism [OR 3.21 (95% CI 1.29-9.09), OR 3.69 (95% CI 1.45-10.9), respectively], when adjusting for country of origin, the duration the child was breastfed, and age at operation. The association between the sum of PCBs and cryptorchidism was close to significant [OR 1.92 (95% CI 0.98-4.01)], whereas the association between the sum of PBDEs and cryptorchidism was not [OR 0.86 (95% CI 0.47-1.54)]. There were no associations between unadjusted chemical concentrations and the risk of cryptorchidism. CONCLUSIONS: Prenatal exposure to PCDD/Fs and PCDD/F-like PCBs may be associated with increased risk for cryptorchidism. Our finding does not exclude the possibility of an association between the exposure to PBDEs and cryptorchidism.

No significant effect of angiotensin II receptor blockade on intermediate cardiovascular end points in hemodialysis patients.

Agents blocking the renin-angiotensin-aldosterone system are frequently used in patients with end-stage renal disease, but whether they exert beneficial cardiovascular effects is unclear. Here the long-term effects of the angiotensin II receptor blocker, irbesartan, were studied in hemodialysis patients in a double-blind randomized placebo-controlled 1-year intervention trial using a predefined systolic blood pressure target of 140 mm Hg (SAFIR study). Each group of 41 patients did not differ in terms of age, blood pressure, comorbidity, antihypertensive treatment, dialysis parameters, and residual renal function. Brachial blood pressure decreased significantly in both groups, but there was no significant difference between placebo and irbesartan. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different. Intermediate cardiovascular end points such as central aortic blood pressure, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal brain natriuretic prohormone, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic blood pressure during the study period significantly correlated with changes in both left ventricular mass and arterial stiffness. Thus, significant effects of irbesartan on intermediate cardiovascular end points beyond blood pressure reduction were absent in hemodialysis patients.

The impact of the COVID-19 lockdown on birthweight among singleton term birth in Denmark.

In Denmark, a nationwide COVID-19 lockdown was implemented on March 12, 2020 and eased on April 14, 2020. The COVID-19 lockdown featured reduced prevalence of extremely preterm or extremely low birthweight births. This study aims to explore the impact of this COVID-19 lockdown on term birthweights in Denmark. We conducted a nationwide register-based cohort study on 27,870 live singleton infants, born at term (weeks 37-41), between March 12 and April 14, 2015-2020, using data from the Danish Neonatal Screening Biobank. Primary outcomes, corrected for confounders, were birthweight, small-for-gestational-age (SGA), and large-for-gestational-age (LGA), comparing the COVID-19 lockdown to the previous five years. Data were analysed using linear regression to assess associations with birthweight. Multinomial logistic regression was used to assess associations with relative-size-for-gestational-age (xGA) categories. Adjusted mean birthweight was significantly increased by 16.9 g (95% CI = 4.1-31.3) during the lockdown period. A dip in mean birthweight was found in gestational weeks 37 and 38 balanced by an increase in weeks 40 and 41. The 2020 lockdown period was associated with an increased LGA prevalence (aOR 1.13, 95% CI = 1.05-1.21). No significant changes in proportions of xGA groups were found between 2015 and 2019. The nationwide COVID-19 lockdown resulted in a small but significant increase in birthweight and proportion of LGA infants, driven by an increase in birthweight in gestational weeks 40 and 41.

Outcome of Acquired Fanconi Syndrome Associated with Ingestion of Jerky Treats in 30 Dogs.

Acquired canine proximal renal tubulopathy (Fanconi syndrome) related to excessive ingestion of jerky treats has been recognized since 2007. This study aimed to improve knowledge about the syndrome's characteristics, especially long-term outcome. By reaching out to veterinarians and dog owners, dogs suspected of jerky induced Fanconi syndrome were identified. The dog's medical records were reviewed, and owners interviewed. Data was analyzed using linear mixed models (p < 0.05 was considered statistically significant) and descriptive statistics are reported. Thirty dogs, median body weight 6.8 (range 1.2−59) kg and age 6.5 (0.5−14) years, were enrolled as suspected cases based on history of jerkey ingestion and confirmed normoglycemic/hypoglycemic glycosuria. Clinical signs included polydipsia (23/30), polyuria (21/30), lethargy (19/30), weight loss (15/30), hyporexia (11/30), vomiting (7/30), diarrhea (7/30) and no clinical signs (2/30). Para-clinical findings included azotemia (6/28), hypophosphatemia (9/25), metabolic acidosis (3/8), hypokalemia (6/20), proteinuria (13/26), aminoaciduria (4/4), hematuria (22/29) and ketonuria (7/27). Clinical signs resolved in 22/28 within 11 (0.3−52) weeks and glycosuria resolved in 28/30 within 6.5 (1−31) weeks. There were no associations between serum creatinine and urea and the amount/duration of jerky ingestion. Serum symmetric dimethylarginine concentrations were only available for a few dogs, therefore no conclusion was achieved on a possible association with duration of jerky ingestion. Apart from a larger percentage of dogs achieving complete recovery, the current findings are in agreement with previous reports.

Alterations in Healthy Adult Canine Faecal Microbiome and Selected Metabolites as a Result of Feeding a Commercial Complete Synbiotic Diet with Enterococcus faecium NCIMB 10415.

In dogs, the use of probiotics for preventive or therapeutic purposes has become increasingly common, however the evidence for beneficial effects are often limited. The aim of this study was to investigate the effects of feeding a diet containing Enterococcus faecium NCIMB 10415 on faecal quality, faecal short-chain fatty acid concentrations, serum concentrations of cholesterol, triglycerides, cobalamin and folate as well as faecal microbiome in adult dogs. Eleven healthy client owned dogs were enrolled in a randomized, double-blinded crossover study. All dogs were fed the same balanced diet with or without incorporation of Enterococcus faecium NCIMB 10415 for 16 days each. Blood and faecal samples were collected at baseline and during the feeding trial and owners recorded daily faecal scores. An Enterococcus spp. ASV, likely representing E. faecium NCIMB 10415 was detected in the faecal microbiome of some dogs 18-19 days after withdrawal of oral supplementation. Inclusion of E. faecium decreased circulating cholesterol (p = 0.008) compared to baseline. There were no differences in cholesterol concentrations between diets. Owners reported 0.6 ± 0.3) days less of loose stools compared to the control diet. Comparing to baseline, both diets significantly increased faecal concentration of acetate and butyrate, decreased serum cobalamin and increased faecal microbial diversity. Decreased serum cobalamin, and increased faecal acetate correlated with decreases in the Fusobacterium, Streptococcus, Blautia, and Peptoclostridium. Except for effects on circulating cholesterol and faecal score, effects were observed regardless of the addition of E. faecium. It is therefore likely that these effects can be contributed to dietary prebiotic effects on the faecal microbiome.

Distinct sites of intracellular production for Alzheimer's disease A beta40/42 amyloid peptides.

The Alzheimer amyloid precursor protein (APP) is cleaved by several proteases, the most studied, but still unidentified ones, are those involved in the release of a fragment of APP, the amyloidogenic beta-protein A beta. Proteolysis by gamma-secretase is the last processing step resulting in release of A beta. Cleavage occurs after residue 40 of A beta [A beta(1-40)], occasionally after residue 42 [A beta(1-42)]. Even slightly increased amounts of this A beta(1-42) might be sufficient to cause Alzheimer's disease (AD) (reviewed in ref. 1, 2). It is thus generally believed that inhibition of this enzyme could aid in prevention of AD. Unexpectedly we have identified in neurons the endoplasmic reticulum (ER) as the site for generation of A beta(1-42) and the trans-Golgi network (TGN) as the site for A beta(1-40) generation. It is interesting that intracellular generation of A beta seemed to be unique to neurons, because we found that nonneuronal cells produced significant amounts of A beta(1-40) and A beta(1-42) only at the cell surface. The specific production of the critical A beta isoform in the ER of neurons links this compartment with the generation of A beta and explains why primarily ER localized (mutant) proteins such as the presenilins could induce AD. We suggest that the earliest event taking place in AD might be the generation of A beta(1-42) in the ER.

Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: A systematic review.

BACKGROUND: Congenital heart defects (CHDs) are the most common congenital malformations. The aetiology of CHDs is complex. Large cohort studies and systematic reviews and meta-analyses based on these have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hypertension, and preeclampsia, all conditions that can be related to insulin resistance or hyperglycaemia. However, the clinical reality is that these conditions often occur simultaneously. The aim of this review is, in consequence, both to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia and CHDs in the offspring, as well as the significance of combinations, such as metabolic syndrome, as risk factors. METHODS: A systematic literature search of papers published between January 1, 1990 and January 14, 2021 was conducted using PubMed and Embase. Studies were eligible if they were published in English and were case-control or cohort studies. The exposures of interest were maternal overweight or obesity, hypertension, preeclampsia, diabetes, dyslipidaemia, and/or metabolic syndrome, and the outcome of interest was CHDs in the offspring. Furthermore, the studies were included according to a quality assessment score. RESULTS: Of the 2,250 identified studies, 32 qualified for inclusion. All but one study investigated only the individual metabolic disorders. Some disorders (obesity, gestational diabetes, and hypertension) increased risk of CHDs marginally whereas pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs, without consistent differences between CHD subtypes. A single study suggested a possible additive effect of maternal obesity and gestational diabetes. CONCLUSIONS: Future studies of the role of aberrations of the glucose-insulin homeostasis in the common aetiology and mechanisms of metabolic disorders, present during pregnancy, and their association, both as single conditions and-particularly-in combination, with CHDs are needed.

Direct Cu-mediated aromatic 18F-labeling of highly reactive tetrazines for pretargeted bioorthogonal PET imaging.

Pretargeted imaging can be used to visualize and quantify slow-accumulating targeting vectors with short-lived radionuclides such as fluorine-18 - the most popular clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-lived radionuclides. Currently, the tetrazine ligation is the most popular bioorthogonal reaction for pretargeted imaging, but a direct 18F-labeling strategy for highly reactive tetrazines, which would be highly beneficial if not essential for clinical translation, has thus far not been reported. In this work, a simple, scalable and reliable direct 18F-labeling procedure has been developed. We initially studied the applicability of different leaving groups and labeling methods to develop this procedure. The copper-mediated 18F-labeling exploiting stannane precursors showed the most promising results. This approach was then successfully applied to a set of tetrazines, including highly reactive H-tetrazines, suitable for pretargeted PET imaging. The labeling succeeded in radiochemical yields (RCYs) of up to approx. 25%. The new procedure was then applied to develop a pretargeting tetrazine-based imaging agent. The tracer was synthesized in a satisfactory RCY of ca. 10%, with a molar activity of 134 ± 22 GBq µmol-1 and a radiochemical purity of >99%. Further evaluation showed that the tracer displayed favorable characteristics (target-to-background ratios and clearance) that may qualify it for future clinical translation.

Stability and profiling of urinary microRNAs in healthy cats and cats with pyelonephritis or other urological conditions.

BACKGROUND: Specific biomarkers of pyelonephritis (PN) in cats are lacking. MicroRNAs (miRNAs) have diagnostic potential in human nephropathies. OBJECTIVES: To investigate the presence/stability of miRNAs in whole urine of cats and the discriminatory potential of selected urinary miRNAs for PN in cats. ANIMALS: Twelve healthy cats, 5 cats with PN, and 13 cats with chronic kidney disease (n = 5), subclinical bacteriuria (n = 3), and ureteral obstructions (n = 5) recruited from 2 companion animal hospitals. METHODS: Prospective case-control study. Expression profiles of 24 miRNAs were performed by quantitative PCR (qPCR). Effect of storage temperature (4°C [24 hours], -20°C, and -80°C) was determined for a subset of miRNAs in healthy cats. RESULTS: Urinary miR-4286, miR-30c, miR-204, miR4454, miR-21, miR-16, miR-191, and miR-30a were detected. For the majority of miRNAs tested, storage at 4°C and -20°C resulted in significantly lower miRNA yield compared to storage at -80°C (mean log2fold changes across miRNAs from -0.5 ± 0.4 SD to -1.20 ± 0.4 SD (4°C versus -80°C) and from -0.7 ± 0.2 SD to -1.20 ± 0.3 SD (-20°C versus -80°C)). Cats with PN had significantly upregulated miR-16 with a mean log2fold change of 1.0 ± 0.4 SD, compared with controls (-0.1 ± 0.2, P = .01) and other urological conditions (0.6 ± 0.3, P = .04). CONCLUSIONS: Upregulation of miR16 might be PN-specific, pathogen-specific (Escherichia coli), or both.

Subclinical bacteriuria in a mixed population of 179 middle-aged and elderly cats: a prospective cross-sectional study.

OBJECTIVES: Subclinical bacteriuria (SBU) is the presence of bacteria in urine with no clinical evidence of lower urinary tract disease. The aims of this study were to investigate if being overweight and/or obesity predispose cats to SBU, to investigate previously reported risk factors and to determine the prevalence of SBU in a prospectively sampled cohort of middle-aged and elderly cats. METHODS: Cats aged ⩾6 years presenting to the University Hospital for Companion Animals in Copenhagen from 2015-2019 for causes unrelated to the lower urinary tract were eligible for enrolment. Body condition scoring was performed on a 9-point scale. Overweight was defined as a body condition score (BCS) ⩾6 and obese as a BCS ⩾8. The correlation between SBU and the variables of sex, healthy/diseased, age, BCS and comorbidities (chronic kidney disease, diabetes mellitus, hyperthyroidism, hepatic disorders and gastrointestinal disease) were analysed by binominal logistic regression. RESULTS: In total, 179 cats ranging from 6-20 (median 10) years of age were included. SBU was identified in 11/179 cats (6.1%). Being overweight was not a significant risk factor (overweight/obese odds ratio [OR] 0.3, 95% confidence interval [CI] 0.06-1.6, relative risk [RR] 0.3 [95% CI 0.05-1.3] vs lean; P = 0.2) and neither was obesity compared with lean and overweight cats (P = 0.99). Female sex (OR 6.2 [95% CI 1.3-30], RR 4.7 [95% CI 1.5-12] vs male; P = 0.02) and the presence of hepatic disease (OR 7.5 [95% CI 1.4-39], RR 5.3 [95% CI 1.3-12]; P = 0.02) were significant risk factors. CONCLUSIONS AND RELEVANCE: The prevalence of SBU in cats is low, and being overweight/obese was not identified as a predisposing factor. The increased risk associated with hepatic disease has not been previously reported, and further studies are needed to confirm this finding.

Acquired cryptorchidism is frequent in infancy and childhood.

Accurate prevalence data for acquired cryptorchidism are currently sparse and systematic prospective studies have not yet been reported. Our aim was to determine the prevalence of testicular ascent in childhood. In a prospective longitudinal population-based child cohort from Copenhagen, Denmark (1997-2007), testicular position was examined according to a standardised protocol in a total of 1072 boys, at birth (n = 1051), at 3 months (n = 983), 18 months (n = 888), 36 months (n = 790) and again once between 4 1/2 and 10 years of age (n = 509). Ascensus testis was defined as ascent of the testis into a cryptorchid position after normal scrotal position at birth. A congenital cryptorchid testis with spontaneous postnatal descent followed by recurrence of cryptorchidism was named recurrent cryptorchidism. Ascensus testis occurred in 0.2%, 0.6% and 0.6% of boys at 3, 18 and 36 months of age respectively. When including recurrent cryptorchidism the prevalence was 0.2%, 1.2% and 0.8% respectively. Ascensus testis accounts for 58% of all cases of cryptorchidism (congenital and acquired) at 18 months, 71% at 36 months and thereafter 69%. Ascensus testis accounts for more than half of cryptorchid testes seen in childhood and occurs in both previously scrotal and cryptorchid testes. We therefore recommend that all boys should have testis position checked regularly during childhood, at least up to 3 years of age.

Concentrations of persistent organochlorine compounds in human milk and placenta are higher in Denmark than in Finland.

BACKGROUND: A significantly reduced male reproductive health status, including a higher prevalence of cryptorchidism and hypospadias, has been documented in Danish men compared with Finnish men. Exposure to environmental pollutants with endocrine disrupting activities has been suggested as a possible contributing factor. In this study, we investigated whether there was a difference in milk and placental concentrations of persistent organohalogen compounds, between the two countries. METHODS: Organohalogens were analysed by high-resolution gas chromatography-high-resolution mass spectrometry in human milk samples from Finland (n = 65) and Denmark (n = 65) and in placentas from Finland (n = 112) and Denmark (n = 168). RESULTS: 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDE) was the dominant pollutant. beta-Hexa-chloro-cyclohexane (beta-HCH), hexachlorobenzene (HCB), endosulfan-I, dieldrin, oxychlordane (OXC), cis-heptachloroepoxide (c-HE) and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) were the other main organochlorines detected. Danish samples had significantly higher concentrations of p,p'-DDE, p,p'-DDT, beta-HCH, HCB, dieldrin, c-HE and OXC than did the Finnish samples. Levels of organobrominated compounds were very low and most were undetectable in the majority of samples. BB-153 and BB-155 were the most abundant polybromobiphenyl congeners. BB-153 was more abundant in Danish milk samples compared with Finnish samples, whereas BB-155 was more abundant in the Finnish milk. CONCLUSIONS: The organochlorine levels were higher in Danish, than in Finnish, samples, suggesting a higher exposure for Danish infants.