Kirsten A. Boisen

Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age.

Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis. Design We obtained biologic samples from a prospective Danish–Finnish cohort study on cryptorchidism from 1997 to 2001. We analyzed individual breast milk samples collected as additive aliquots 1–3 months postnatally (n = 130; 62 cryptorchid/68 healthy boys) for phthalate monoesters [mono-methyl phthalate (mMP), mono-ethyl phthalate (mEP), mono-n-butyl phthalate (mBP), mono-benzyl phthalate (mBzP), mono-2-ethylhexyl phthalate (mEHP), mono-isononyl phthalate (miNP)]. We analyzed serum samples (obtained in 74% of all boys) for gonadotropins, sex-hormone binding globulin (SHBG), testosterone, and inhibin B. Results All phthalate monoesters were found in breast milk with large variations [medians (minimum–maximum)]: mMP 0.10 (< 0.01–5.53 μg/L), mEP 0.95 (0.07–41.4 μg/L), mBP 9.6 (0.6–10,900 μg/L), mBzP 1.2 (0.2–26 μg/L), mEHP 11 (1.5–1,410 μg/L), miNP 95 (27–469 μg/L). Finnish breast milk had higher concentrations of mBP, mBzP, mEHP, and Danish breast milk had higher values for miNP (p = 0.0001–0.056). No association was found between phthalate monoester levels and cryptorchidism. However, mEP and mBP showed positive correlations with SHBG (r = 0.323, p = 0.002 and r = 0.272, p = 0.01, respectively); mMP, mEP, and mBP with LH:free testosterone ratio (r = 0.21–0.323, p = 0.002–0.044) and miNP with luteinizing hormone (r = 0.243, p = 0.019). mBP was negatively correlated with free testosterone (r = −0.22, p = 0.033). Other phthalate monoesters showed similar but nonsignificant tendencies. Conclusions Our data on reproductive hormone profiles and phthalate exposures in newborn boys are in accordance with rodent data and suggest that human Leydig cell development and function may also be vulnerable to perinatal exposure to some phthalates. Our findings are also in line with other recent human data showing incomplete virilization in infant boys exposed to phthalates prenatally.

Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries.

BACKGROUNDnSeveral investigators have shown striking differences in semen quality and testicular cancer rate between Denmark and Finland. Since maldescent of the testis is a shared risk factor for these conditions we undertook a joint prospective study for the prevalence of congenital cryptorchidism.nnnMETHODSn1068 Danish (1997-2001) and 1494 Finnish boys (1997-99) were consecutively recruited prenatally. We also established prevalence data for all newborns at Turku University Central Hospital, Finland (1997-99, n=5798). Testicular position was assessed by a standardised technique. All subtypes of congenital cryptorchidism were included, but retractile testes were considered normal.nnnFINDINGSnPrevalence of cryptorchidism at birth was 9.0% (95% CI 7.3-10.8) in Denmark and 2.4% (1.7-3.3) in Finland. At 3 months of age, prevalence rates were 1.9% (1.2-3.0) and 1.0% (0.5-1.7), respectively. Significant geographic differences were still present after adjustment for confounding factors (birthweight, gestational age, being small for gestational age, maternal age, parity, mode of delivery); odds ratio (Denmark vs Finland) was 4.4 (2.9-6.7, p<0.0001) at birth and 2.2 (1.0-4.5, p=0.039) at three months. The rate in Denmark was significantly higher than that reported 40 years ago.nnnINTERPRETATIONnOur findings of increasing and much higher prevalence of congenital cryptorchidism in Denmark than in Finland contribute evidence to the pattern of high frequency of reproductive problems such as testicular cancer and impaired semen quality in Danish men. Although genetic factors could account for the geographic difference, the increase in reproductive health problems in Denmark is more likely explained by environmental factors, including endocrine disrupters and lifestyle.

Self-Reported Barriers to Medication Adherence Among Chronically Ill Adolescents: A Systematic Review

PURPOSEnTo investigate self-reported barriers to medication adherence among chronically ill adolescents, and to investigate whether barriers are unique to specific chronic diseases or more generic across conditions.nnnMETHODSnA systematic search of Web of Science, PubMed, Embase, PsycINFO, and CINAHL from January 2000 to May 2012 was conducted. Articles were included if they examined barriers to medication intake among chronically ill adolescents aged 13-19 years. Articles were excluded if adolescents views on barriers to adherence were not separated from younger childrens or caregivers views. Data was analyzed using a thematic synthesis approach.nnnRESULTSnOf 3,655 records 28 articles with both quantitative, qualitative, and q-methodology study designs were included in the review. The synthesis led to the following key themes: Relations, adolescent development, health and illness, forgetfulness, organization, medicine complexity, and financial costs. Most reported barriers to adherence were not unique to specific diseases.nnnCONCLUSIONnSome barriers seem to be specific to adolescence; for example, relations to parents and peers and adolescent development. Knowledge and assessment of barriers to medication adherence is important for both policy-makers and clinicians in planning interventions and communicating with adolescents about their treatment.

Barriers to adherence in adolescents and young adults with cystic fibrosis: a questionnaire study in young patients and their parents

Background Treatment adherence is crucial in patients with cystic fibrosis, but poor adherence is a problem, especially during adolescence. Identification of barriers to treatment adherence and a better understanding of how context shapes barriers is of great importance in the disease. Adolescent reports of barriers to adherence have been studied, but studies of their parents’ experience of such barriers have not yet been carried out. The aim of the present study was to explore barriers to treatment adherence identified by young patients with cystic fibrosis and by their parents. Methods A questionnaire survey of a cohort of young Danish patients with cystic fibrosis aged 14–25 years and their parents was undertaken. Results Barriers to treatment adherence were reported by 60% of the patients and by 62% of their parents. Patients and parents agreed that the three most common barriers encountered were lack of time, forgetfulness, and unwillingness to take medication in public. We found a significant positive correlation between reported number of barriers and perceived treatment burden. We also found a statistically significant relationship between the reported number of barriers and treatment adherence. A significant association was found between the number of barriers and the reactions of adolescents/young adults and those of their mothers and fathers, and between the number of barriers and the way the family communicated about cystic fibrosis. Conclusion The present study showed that the majority of adolescents with cystic fibrosis and their parents experienced barriers to treatment adherence. Agreement between adolescents and their parents regarding the level and types of barriers indicates an opportunity for close cooperation between adolescents, their parents, and health care professionals in overcoming adolescent adherence problems.

Increased kidney growth in formula-fed versus breast-fed healthy infants

A high protein intake results in increased kidney growth and glomerular filtration rate in human adults and young rats. It is unknown whether kidney size in young infants is influenced by increased protein intake in formula-fed compared with breast-fed infants. We investigated the effect of formula versus breast feeding on kidney growth in a cohort of 631 healthy children examined at birth, and at 3 and 18xa0months of age. Kidney size was determined by ultrasonography and related to gender, age, body size, and feeding category (fully breast fed, partially breast fed, or fully formula fed at 3xa0months). Serum urea nitrogen, serum creatinine, and estimated creatinine clearance were measured at 3xa0months of age. Kidney growth and serum urea nitrogen were significantly increased in partially or fully formula-fed 3-month-old infants. This effect was more pronounced in boys than in girls. The changes in relative kidney size were temporary, as they did not persist at 18xa0months of age, when all children received a normal mixed diet. The immediate renal effects of formula feeding should be taken into consideration for recommendations concerning infant feeding. Whether there are any long-term effects of early increased protein intake on later kidney function remains to be seen.

Kidney growth in 717 healthy children aged 0–18 months: a longitudinal cohort study

Kidney size is an important parameter in the evaluation of children with renal disease. However, reference materials for kidney size in healthy children have been limited beyond the neonatal period. We performed a longitudinal cohort study of 717 healthy children born at term with normal birth weight. Kidney size and shape were determined by ultrasonography and related to gender, age, and body size (weight, length, body surface area, skinfold thickness) at 0, 3, and 18xa0months of age. Gender-differentiated reference charts were established. Boys had significantly larger kidney volumes than girls (P<0.001) and larger relative volumes (kidney volume/weight) at 0 and 3xa0months (P<0.001), but not at 18xa0months of age. The best single predictor of gender-differentiated kidney volume was weight. Relative kidney volume changed with increasing age and height in a two-phase pattern: an initial decrease until a height of 65–70xa0cm was reached followed by a stable level. In conclusion, kidney size was significantly influenced by gender, age, and body composition. Relative kidney volume decreased with increasing age and height in a two-phase pattern. These characteristic changes in kidney volume indicated that infant kidney growth might be influenced by sex steroids and growth hormone in addition to body composition.

Gender difference in breast tissue size in infancy: correlation with serum estradiol.

Breast tissue in newborn infants is considered to be physiologic and mainly related to exposure to maternal hormones in utero or through breast-feeding. However, controversy exists as to whether breast tissue in later infancy is under the influence of endogenous hormones. Children at 2–4 mo of age have a surge of reproductive hormones, including estradiol, which may affect the mammary gland. In a prospective cohort study of 1126 healthy, 3-mo-old infants, breast tissue size and reproductive hormones were measured. We found that palpable breast tissue (diameter ≥3 mm) is a common physiologic condition present in 78.9% of children, significantly more frequent (p < 0.001) and larger (p < 0.001) in girls than in boys. Girls had significantly higher median estradiol levels than boys (30.0 versus 21.0 pmol/L, p < 0.001). In a multiple regression model including breast tissue size given as quartiles as the dependent variable and weight for gestational age, subscapular skinfold, weight at 3 mo of age and serum estradiol as independent variables, a gender difference was shown. In girls, the estradiol level was positively (p < 0.03) correlated to breast quartile. In boys, no correlations were found. Whether the stimulation of the mammary gland in infancy represents a developmental window that is of biologic significance for breast development and pathology in adulthood remains to be defined.

Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis

BackgroundCystic fibrosis (CF) is a life shortening disease, however prognosis has improved and the adult population is growing. Most adults with cystic fibrosis live independent lives and balance the demands of work and family life with a significant treatment burden. The aim of this study was to examine the relationships among treatment adherence, symptoms of depression and health-related quality of life (HRQoL) in a population of young adults with CF.MethodsWe administered three standardized questionnaires to 67 patients with CF aged 18–30xa0years; Morisky Medication Adherence Scale, Major Depression Inventory, and Cystic Fibrosis Questionnaire-Revised.ResultsThere was a response rate of 77xa0% and a majority of the young adults (84xa0%) were employed or in an education program. Most participants (74xa0%) reported low adherence to medications. One third (32.8xa0%) of the participants reported symptoms of depression. HRQoL scores were especially low on Vitality and Treatment Burden, and symptoms of depression were associated with low HRQoL scores (pxa0<xa00.01) with medium to large deficits across on all HRQoL domains (Cohen’s d 0.60–1.72) except for the domain treatment burden. High depression symptom scores were associated with low adherence (rxa0=xa0−0.412, pxa0<xa00.001).ConclusionsDespite improved physical health, many patients with CF report poor adherence, as well as impaired mental wellbeing and HRQoL. Thus, more attention to mental health issues is needed.

Quality of life in adolescents and young adults with CHD is not reduced: a systematic review and meta-analysis.

PURPOSEnWe performed a systematic review and meta-analysis of observational studies assessing quality of life in adolescents and young adults born with CHD compared with age-matched controls.nnnMETHODSnWe carried out a systematic search of the literature published in Medline, Embase, PsychINFO, and the Cochrane Librarys Database (1990-2013); two authors independently extracted data from the included studies. We used the Newcastle-Ottawa scale for quality assessment of studies. A random effects meta-analysis model was used. Heterogeneity was assessed using the I2-test.nnnRESULTSnWe included 18 studies with 1786 patients. The studies were of acceptable-to-good quality. The meta-analysis of six studies on quality of life showed no significant difference - mean difference: -1.31; 95% confidence intervals: -6.51 to +3.89, I2=90.9% - between adolescents and young adults with CHD and controls. Similar results were found in 10 studies not eligible for the meta-analysis. In subdomains, it seems that patients had reduced physical quality of life; however, social functioning was comparable or better compared with controls.nnnCONCLUSIONnFor the first time in a meta-analysis, we have shown that quality of life in adolescents and young adults with CHD is not reduced when compared with age-matched controls.

Perhaps I will die young. Fears and worries regarding disease and death among Danish adolescents and young adults with cancer. A mixed method study.

PurposeA cross-sectional national study was initiated in order to evaluate healthcare services and survivorship from the perspective of Danish adolescents and young adults (AYAs) with cancer. The purpose of the paper was to examine (Q1) to what extend Danish AYAs experienced fears and worries about dying; (Q2) with whom, if anyone, they had shared those worries; and finally, (Q3) how fears and worries influenced their daily life. The emphasis will be on Q3.MethodsA 151-item questionnaire (including two closed- and one open-ended questions about fears of death and dying) was distributed among all 15–29-year-old Danes registered with a cancer diagnosis from 2009 to 2013. A total study population of 822 persons participated. Data was analyzed using a mixed design of descriptive statistics and qualitative content analysis.ResultsQ1: Almost 80xa0% of AYAs with cancer expressed some worries about death; hereof, more than half of them expressed quite a bit or very much. The analysis showed significant gender differences, whereas age and duration of disease did not have any significant impact on such thoughts. Q2: One third had not talked to anybody about his or her worries. Q3: The analysis resulted in three overall categories: fear of disease and death having little or no influence (nxa0=xa0100), fear influencing in various ways (nxa0=xa0215), and fear of disease and death having a substantial influence (nxa0=xa075).ConclusionsThe majority of AYAs had experienced fears and worries about dying, but one third of them had not talked to anybody about those thoughts. It is an important clinical point that young age does not preclude fears and worries about dying in AYAs with cancer.