C.M. Verhaak

Major depression in adolescent children consecutively diagnosed with mitochondrial disorder

A higher incidence of major depression has been described in adults with a primary oxidative phosphorylation disease. Intriguingly however, not all patients carrying the same mutation develop symptoms of major depression, pointing out the significance of the interplay of genetic and non-genetic factors in the etiology. In a series of paediatric patients evaluated for mitochondrial dysfunction, out of 35 children with a biochemically and genetically confirmed mitochondrial disorder, we identified five cases presenting with major depression prior to the diagnosis. The patients were diagnosed respectively with mutations in MTTK, MTND1, POLG1, PDHA1 and the common 4977 bp mtDNA deletion. Besides cerebral lactic acidemia protein and glucose concentrations, immunoglobins, anti-gangliosides and neurotransmitters were normal. No significant difference could be confirmed in the disease progression or the quality of life, compared to the other, genetically confirmed mitochondrial patients. In three out of our five patients a significant stress life event was confirmed. We propose the abnormal central nervous system energy metabolism as the underlying cause of the mood disorder in our paediatric patients. Exploring the genetic etiology in children with mitochondrial dysfunction and depression is essential both for safe medication and adequate counselling.

Standardized Multidisciplinary Evaluation Yields Significant Previously Undiagnosed Morbidity in Adult Women with Turner Syndrome

CONTEXT Besides short stature and gonadal dysgenesis, Turner syndrome (TS) is associated with various abnormalities. Adults with TS have a reduced life expectancy, mainly related to structural abnormalities of the heart and aorta, and an increased risk of atherosclerosis. OBJECTIVE Our objective was to investigate the yield of an initial standardized multidisciplinary screening in adult TS patients. DESIGN AND SETTING This was an observational study at a multidisciplinary care unit for adult women with TS. PARTICIPANTS Participants were adult women with TS (n = 150). Mean age was 31.0 ± 10.4 yr, with 47% karyotype 45,X. INTERVENTIONS All women were consulted by an endocrinologist, a gynecologist, a cardiologist, an otorhinolaryngologist, and when indicated, a psychologist. The screening included magnetic resonance imaging of the heart and aorta, echocardiography, electrocardiogram, dual-energy x-ray absorptiometry, renal ultrasound, audiogram, and laboratory investigations according to international expert recommendations. MAIN OUTCOME MEASURES New diagnoses and prevalence of TS-associated morbidity were evaluated. RESULTS Thirty percent of patients currently lacked medical follow-up, and 15% lacked estrogen replacement therapy in the recent last years. The following disorders were newly diagnosed: bicuspid aortic valve (n = 13), coarctation of the aorta (n = 9), elongation of the transverse aortic arch (n = 27), dilation of the aorta (n = 34), osteoporosis (n = 8), osteopenia (n = 56), renal abnormalities (n = 7), subclinical hypothyroidism (n = 33), celiac disease (n = 3), glucose intolerance (n = 12), dyslipidemia (n = 52), hypertension (n = 39), and hearing loss warranting a hearing aid (n = 8). Psychological consultation was needed in 23 cases. CONCLUSIONS Standardized multidisciplinary evaluation of adult women with TS as advocated by expert opinion is effective and identifies significant morbidity. Girls with TS benefit from a careful transition to ongoing adult medical care.

Why we should talk about compliance with assisted reproductive technologies (ART): a systematic review and meta-analysis of ART compliance rates

BACKGROUND The goal of this systematic review and meta-analysis was to estimate the rate of compliance with assisted reproductive technologies (ART) and examine its relationship with treatment success rates. METHODS Six databases were systematically searched from 1978 to December 2011. Studies were included if they reported data on patient progression through three consecutive standard ART cycles. Compliance was estimated for the first three ART cycles (typical ART Regimen Compliance, TARC) and after the first and the second failed cycles (CAF1, CAF2). Treatment success rates for all patients who started ART and for those who fully complied with the three ART cycles were estimated. RESULTS Ten studies with data for 14 810 patients were included. TARC was 78.2% [95% confidence interval (CI) 68.8–85.3%], CAF1 was 81.8% (73.3–88.1%) and CAF2 was 75.3% (68.2–81.2%). The overall success rate was 42.7% (32.6–53.6%) for all patients starting ART and 57.9% (49.4–65.9%) for those who complied with three ART cycles. Compliance rates did not vary according to study quality, but TARC was higher for studies that reported data on doctor-censored patients versus those that did not (84.2% 95% CI 75.5–90.2 versus 70.6% 95% CI 58.3–80.5, P = 0.043). Analysis of funnel plots and the Egger test indicated publication bias for CAF1. CONCLUSIONS Findings from this meta-analysis should reassure clinics and patients that most patients are able to comply with three cycles of ART. Compliers could increase their chances of success by as much as 15%. A more detailed assessment of compliance requires monitoring long-term treatment trajectories through the creation of national registries.

Prenatal maternal psychological stress and childhood asthma and wheezing: a meta-analysis

The aim of this study was to systematically review and meta-analyse observational studies on prenatal maternal psychological stress and the subsequent development of asthma and wheezing in early childhood. All available published literature from 1960 until November 2013 was systematically searched through electronic databases (PubMed, Embase, PsycInfo and Web of Science). All observational studies assessing associations between any form of prenatal maternal psychological stress and respiratory morbidity in the child were included. Data extraction, quality assessment and meta-analyses were performed. The overall meta-analysis included 10 studies and showed that the prevalence of wheezing, asthma and other respiratory symptoms is higher in children of mothers who were exposed to or experienced some form of psychological stress during pregnancy than in mothers who did not (pooled OR 1.56 (95% CI 1.36–1.80)). Comparable results were observed in subgroup analyses of stress exposure, perceived stress, asthma and wheezing. This study demonstrates that prenatal maternal psychological stress is associated with respiratory morbidity, including asthma and wheezing in the child. Future studies examining the early origins of asthma and wheezing need to account for the impact of prenatal maternal stress. Study showing an association between prenatal psychological stress and subsequent respiratory morbidity in children http://ow.ly/USkLN

Depressive behaviour in children diagnosed with a mitochondrial disorder.

A higher incidence of depression has been described in adults with primary oxidative phosphorylation disease. We evaluated the psychological characteristics of eighteen non-retarded pediatric patients diagnosed with a disorder of the oxidative phosphorylation. We found significantly higher rate of withdrawn, depressive behaviour compared to population norm scores, to children with other types of inborn errors of metabolism and also in comparison to patients with Sotos syndrome. The occurrence of depressive behaviour showed no correlation with the degree of mitochondrial dysfunction. These findings support the hypothesis that mood disorders could be associated to abnormal cerebral energy metabolism.

Rationale and Design of the PRegnancy and Infant DEvelopment (PRIDE) Study

Background To optimise the health of pregnant women and their children by evidence-based primary and secondary prevention, more scientific knowledge is needed. To overcome the methodological limitations of many studies on pregnancy and child health, which often use a retrospective design, we established the PRIDE (PRegnancy and Infant DEvelopment) Study. Methods and Results The PRIDE Study is a large prospective cohort study that aims at including 150 000–200 000 women in early pregnancy to study a broad range of research questions pertaining to pregnancy complications, maternal and child health, and adverse developmental effects in offspring. Women are invited to participate by their prenatal care provider before or at their first prenatal care visit and are asked to fill out web-based questionnaires in gestational weeks 8–10, 17, and 34, as well as biannually throughout childhood. In addition, a food frequency questionnaire and a paternal questionnaire are administered and medical records are consulted. Multiple validation studies will be conducted and paper-and-pencil questionnaires are available for women who cannot or do not want to participate through the Internet. For subgroups of participants, blood and saliva samples for genetic and biochemical analyses are being collected. The pilot phase, which started in July 2011, showed a response rate of 47%. Recruitment will eventually cover all of the Netherlands. Conclusions We expect that this study, which will be the largest birth cohort in the world so far, will provide new insights in the aetiology of disorders and diseases that originate in pregnancy. The PRIDE Study is open for collaboration.

Absence from work and emotional stress in women undergoing IVF or ICSI: An analysis of IVF‐related absence from work in women and the contribution of general and emotional factors

Objective. To assess productivity losses due to absence from work during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and to describe the pattern of IVF‐related absence from work. Additionally, the influence of general and psychological variables on IVF‐related absence from work was analyzed. Design. Prospective cohort study. Setting. Eight IVF hospitals participated in the study. Sample. Women undergoing their first treatment with IVF/ICSI. Methods. The Health and Labour Questionnaire (HLQ) was used to estimate the costs of IVF‐related absence from work (n = 384). Diaries were used to collect background information and reasons for IVF‐related absence. Psychological data were derived using the Spielberger State and Trait Anxiety Inventory (STAI), the Beck Depression Inventory for Primary Care (BDI‐PC) and the Inventory Social Relations and the Illness Cognition Questionnaire. Regression analyses were performed using two models, one without and one with psychological data, to assess the impact of the different variables on IVF‐related absence from work. Main outcome measure. IVF‐related absence from work and the costs of productivity losses due to IVF/ICSI per treatment. Results. Overall absence from work during IVF/ICSI treatment was on average 33 hours, of which 23 hours were attributed to IVF/ICSI. Costs of productivity losses due to IVF/ICSI were €596 per woman. Significant predictors of IVF‐related absence from work were the number of hours of paid work, age and self‐reported physical and/or emotional problems due to IFV treatment. Conclusions. Women experiencing emotional complaints and women with physical complaints due to IVF/ICSI reported significantly more IVF‐related absence from work.

Parents' perspectives on the unforeseen finding of a fetal sex chromosomal aneuploidy

To investigate the parental perspectives of being confronted with an unforeseen fetal sex chromosomal aneuploidy (SCA), in light of the fact that this accidental finding is avoidable by rapid aneuploidy detection (RAD).

Do children make you happier? Sustained child-wish and mental health in women 11–17 years after fertility treatment

STUDY QUESTION Are fertility treatment-related factors, parenthood status and sustained child-wish associated with womens long-term mental health? SUMMARY ANSWER Sustaining a child-wish is more strongly associated with womens long-term mental health than fertility treatment-related factors and parenthood status. WHAT IS KNOWN ALREADY About one-third of the couples starting fertility treatment do not achieve parenthood and have to adjust to an unfulfilled child-wish. In women, remaining childless after treatment is associated with less favourable mental health. It is unclear if this is only related to their childlessness or if adjustment after unsuccessful treatment is affected by other variables. These include diagnostic and treatment-related factors (cause of fertility problems, age at first consultation, type and number of treatments) and the psychological ability to come to terms with the unfulfilled child-wish. Differentiating the relative contribution of these factors to womens long-term mental health will provide useful knowledge to support patients adjusting to negative treatment outcomes. STUDY DESIGN, SIZE, DURATION A cross-sectional study with a nationally representative sample of 7148 women who started fertility treatment at any of the 12 IVF hospitals in the Netherlands from 1995 through 2000. Of 16 482 women who were invited to participate, 7148 (43.4%) provided psychological data. PARTICIPANTS/MATERIALS, SETTING, METHODS The average age of women was 47 years and the average age at first fertility consultation was 30 years. Fifty-one per cent of women did IUI and 85% did IVF/ICSI. Ninety per cent of women were married/cohabiting, 20.9% remained childless and 5.9% had a child-wish. Women completed a questionnaire assessing diagnostic and treatment factors (retrospective data), parenthood status, sustained child-wish and mental health. MAIN RESULTS AND THE ROLE OF CHANCE A multiple regression analysis controlling for background variables showed that, first, male factor (P < 0.05) and/or idiopathic infertility (P < 0.001) were associated with better mental health. Secondly, starting fertility treatment at an older age was associated with better mental health (P < 0.01). Thirdly, the interaction between parenthood status and sustained child-wish was significant (P < 0.01). Having a child-wish was associated with worse mental health for women with (β = -0.058, P < 0.01) and without children (β =-0.136, P < 0.001), but associations were stronger for the latter. Predictive factors accounted for <5% of the variation in mental health status in the study population. LIMITATIONS, REASONS FOR CAUTION The sample was large and nationally representative. Response rate was in line with other studies but women without psychological data were less likely to have biological children and 15.9% of non-responders considered the questionnaire to be too confronting or to elicit too emotional memories. This could reflect an underestimation of the proportion of women with a sustained child-wish. WIDER IMPLICATIONS OF THE FINDINGS Sustaining a child-wish is a more important risk for long-term adjustment problems than parenthood status. Women adjust better when they start treatment at older ages and know they were not responsible for the cause of the fertility problem. Fertility staff can play an important role in preparing patients for the possibility of treatment failure and the associated grief process. They can also inform patients about the positive effect of refocusing their life goals. STUDY FUNDING/COMPETING INTERESTS This study was supported by a grant from the Dutch Cancer Society (2006-3631). No competing interests exist. TRIAL REGISTRATION NUMBER N/A.

Teaming up: feasibility of an online treatment environment for adolescents with type 1 diabetes

To evaluate the feasibility of an online interactive treatment environment for adolescents with type 1 diabetes, called Sugarsquare, to supplement usual care.