Background Adrenomedullin (ADM) is a circulating peptide known to regulate vasodilation and vascular integrity. Increased plasma ADM concentrations have been described for several life-threatening conditions, including cardiovascular diseases and septic shock. Reliable methods for the simple quantification of bioactive ADM (bio-ADM) are lacking. Methods Monoclonal antibodies against the amidated C-terminus and middle portion of bio-ADM were generated and used for the development of a 1-step immunometric assay for the specific quantification of bio-ADM in plasma. The assay was developed in a microtiter plate/chemiluminescence label format with a significantly reduced incubation time. Precision, linearity, specimen stability, and distribution of results in healthy subjects were evaluated. Results The use of monoclonal antibodies against predetermined epitopes of bio-ADM enabled the development of an assay for the determination of bio-ADM directly in EDTA plasma. Plasma samples were stable for up to 24 h at ambient temperature and over multiple freeze–thaw cycles without loss of immunoreactivity. The assay had a limit of detection of 3 pg/mL and a limit of quantification of 11 pg/mL. The assay exhibited acceptable linearity characteristics and was not influenced by complement factor H, a putative ADM-binding protein. In healthy subjects, bio-ADM concentrations were all above the limit of detection, and approximately half of them were above the limit of quantification. Conclusions By using monoclonal antibodies with defined epitope specificities, we have developed a simple, rapid, accurate, and sensitive sandwich immunoassay for bio-ADM. The assay is a potentially novel tool to support patient management, particularly in acute care in the field of sepsis and other indications, which are currently being investigated, such as acute heart failure.

Recent proposals suggest early adversity sets in motion particularly chronic and neurobiologically distinct trajectories of internalizing symptoms. However, few prospective studies in high-risk samples delineate distinct trajectories of internalizing symptoms from preschool age onward. We examined trajectories in a high-risk cohort, oversampled for internalizing symptoms, several preschool risk/maintenance factors, and school-age outcomes. Parents of 325 children completed the Strengths and Difficulties Questionnaire on up to four waves of data collection from preschool (3-5 years) to school age (8-9 years) and Preschool Age Psychiatric Assessment interviews at both ages. Multi-informant data were collected on risk factors and symptoms. Growth mixture modelling identified four trajectory classes of internalizing symptoms with stable low, rising low-to-moderate, stable moderate, and stable high symptoms. Children in the stable high symptom trajectory manifested clinically relevant internalizing symptoms, mainly diagnosed with anxiety disorders/depression at preschool and school age. Trajectories differed regarding loss/separation experience, maltreatment, maternal psychopathology, temperament, and stress-hormone regulation with loss/separation, temperament, maternal psychopathology, and stress-hormone regulation (trend) significantly contributing to explained variance. At school age, trajectories continued to differ on symptoms, disorders, and impairment. Our study is among the first to show that severe early adversity may trigger a chronic and neurobiologically distinct internalizing trajectory from preschool age onward.

BackgroundThe incidences of childhood overweight and obesity have increased substantially and with them the prevalence of associated somatic and psychiatric health problems. Therefore, it is important to identify modifiable risk factors for early childhood overweight in order to develop effective prevention or intervention programs. Besides biological factors, familial interactions and parental behavioral patterns may influence children’s weight development. Longitudinal investigation of children at overweight risk could help to detect significant risk and protective factors. We aim to describe infants’ weight development over time and identify risk and protective factors for the incidence of childhood obesity. Based on our findings we will draw up a risk model that will lay the foundation for an intervention/prevention program.Methods/DesignWe present the protocol of a prospective longitudinal study in which we investigate families with children aged from 6 months to 47 months. In half of the families at least one parent is obese (risk group), in the other half both parents are normal weight (control group). Based on developmental and health-psychological models, we consider measurements at three levels: the child, the parents and parent–child-relationship. Three assessment points are approximately one year apart. At each assessment point we evaluate the psychological, social, and behavioral situation of the parents as well as the physical and psychosocial development of the child. Parents are interviewed, fill in questionnaires, and take part in standardized interaction tasks with their child in a feeding and in a playing context in our research laboratory. The quality of these video-taped parent–child interactions is assessed by analyzing them with standardized, validated instruments according to scientific standards.DiscussionStrengths of the presented study are the prospective longitudinal design, the multi-informant approach, including the fathers, and the observation of parent–child interaction. A limitation is the variation in children’s age.

Introduction: Maternal obesity has been shown to be a risk factor for obesity in children and may also affect children's psychosocial outcomes. It is not yet clear whether there are also psycho-emotional mechanisms explaining the effects of maternal weight on young children's weight and psychosocial development. We aimed to evaluate whether maternal body mass index (BMI), mother–child emotional availability (EA), and maternal parenting stress are associated with children's weight and psychosocial development (i.e., internalizing/externalizing symptoms and social competence) and whether these predictors interact with each other.Methods: This longitudinal study included three assessment points (~11 months apart). The baseline sample consisted of N = 194 mothers and their children aged 5–47 months (M = 28.18, SD = 8.44, 99 girls). At t1, we measured maternal weight and height to calculate maternal BMI. We videotaped mother–child interactions, coding them with the EA Scales (fourth edition). We assessed maternal parenting stress with the Parenting Stress Index (PSI) short form. At t1 to t3, we measured height and weight of children and calculated BMI–SDS scores. Children's externalizing and internalizing problems (t1–t3) and social competence (t3, N = 118) were assessed using questionnaires: Child Behavior Checklist (CBCL 1.5–5), Strengths and Difficulties Questionnaire (SDQ: prosocial behavior), and a checklist for behavioral problems at preschool age (VBV 3–6: social-emotional competence).Results: By applying structural equation modeling (SEM) and a latent regression analysis, we found maternal BMI to predict higher BMI–SDS and a poorer psychosocial development (higher externalizing symptoms, lower social competence) in children. Higher parenting stress predicted higher levels of externalizing and internalizing symptoms and lower social competence. Better maternal EA was associated with higher social competence. We found parenting stress to serve as a mediator in the association between maternal weight and children's psychosocial outcomes. Moreover, children of mothers with an elevated BMI were at greater risk of lower social competence only when their mothers showed low levels of maternal EA (moderation).Conclusion: Interventional studies are needed that investigate the causal pathways between parenting stress, mother–child interaction quality and child outcomes. These aspects might be targets to improve the psychosocial development of the offspring of overweight or obese mothers.