Health-related quality of life of adults with spinal muscular atrophy: insights from a nationwide patient registry in Germany.

PURPOSE: Spinal muscular atrophy (SMA) is a rare, autosomal-recessive disease characterized by progressive muscular atrophy and weakness resulting in substantial disability and short life expectancy. The objective of this cross-sectional study was to assess health-related quality of life (HRQoL) of adults with SMA in Germany in the era of disease-modifying therapy. METHODS: Adults with SMA were recruited via the German national TREAT-NMD SMA patient registry. HRQoL was measured using the EQ-5D-5L, the Health Utilities Index Mark III (HUI), and the Short Form (36) Health Survey (SF-36). Estimates were stratified by current best motor function of the lower limb and trunk (i.e., non-sitter, sitter, and walker) and SMA type (i.e., type I, II, and III). RESULTS: A total of 82 adults with SMA (mean age: 42 years, 51% female) self-completed the study questionnaire. The mean EQ-5D-5L utility was estimated at 0.5135 (range across subgroups: 0.31-0.99), mean EQ-VAS at 69.71 (64.67-90.00), mean HUI-derived utility at 0.3171 ( - 0.02-0.96), mean SF-6D utility at 0.6308 (0.58-0.65), and mean SF-36 Physical Component Summary and Mental Health Component Summary scores at 33.78 (9.92-53.10) and 53.49 (21.02-72.25), respectively. CONCLUSIONS: We show that adults with SMA experience considerable impairment across a wide range of health dimensions, including mobility, dexterity, pain, and emotional well-being. However, our results exhibit non-trivial variability across clinical subgroups and HRQoL measures. These data contribute to our understanding of the subjective impact of living with a severely debilitating neuromuscular disease, such as SMA.

Child temperament as a longitudinal predictor of mother-adolescent interaction quality: are effects independent of child and maternal mental health?

Adaptive parent-child interaction plays a major role in healthy child development. Caregiver mental health problems can negatively impact parent-child interaction. In turn, interactional quality is often studied as a predictor of child outcome. However, child characteristics supposedly shape parent-child interactions as well. Given associations between child and caregiver mental health and child temperament, this study aimed at differentiating their effects on dyadic interaction quality in adolescence. Child temperament and character at age 5 were investigated as longitudinal predictors of observed mother-adolescent interactional quality at age 14 in a community sample (N = 76). It was examined whether these effects were independent of maternal and child mental health and earlier dysfunctional interaction. Lower novelty seeking, higher reward dependence, and higher cooperativeness separately predicted higher dyadic interactional quality at age 14. Controlling regressions for dysfunctional interaction at age 5, which was a significant negative predictor of later interactional quality, cancelled out the effects of novelty seeking and cooperativeness. Past or concurrent maternal or child psychopathology did not explain variance in mother-adolescent interaction. Applying backward selection, a model including reward dependence and dysfunctional interaction at age 5 and concurrent maternal stress showed the best fit for explaining dyadic interaction quality. Results suggest that enduring rather than transient child features predict interactional quality in a community sample. Effects of temperament are not better explained by those of psychopathology, but a combination of child, maternal, and dyadic features predicted dyadic behaviour best. Selective prevention should target parenting in the context of challenging child characteristics specifically.

Self-Reported Health-Related Quality of Life of Children with Spinal Muscular Atrophy: Preliminary Insights from a Nationwide Patient Registry in Germany.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare, severely debilitating neuromuscular disease characterized by a wide spectrum of progressive muscular atrophy and weakness. OBJECTIVES: The objective of this pilot study was to estimate self-assessed health-related quality of life (HRQoL) of children with SMA. METHODS: Children with SMA were recruited via the German national TREAT-NMD SMA patient registry and asked to self-complete the following rating-scales: KIDSCREEN-27, KINDL, the PedsQL 3.0 Neuromuscular Module (PedsQL 3.0 NMM), EQ-5D-5L, and the Health Utilities Index (HUI). Estimates were stratified by current best motor function of the lower limb and trunk (i.e., non-sitter, sitter, and walker) and SMA type (i.e., type I, II, and III). RESULTS: In total, 17 children with SMA (mean age: 9.88 years, SD: 4.33 years, range: 5-16 years; 59% female) participated in the study. Across examined strata, the mean KIDSCREEN-27 total score was estimated at between 48.24 and 83.81; the mean KINDL total score at between 60.42 and 76.73; the mean PedsQL 3.0 NMM total score at between 58.00 and 83.83; the mean EQ-5D-5L utility at between 0.31 and 0.99; and the mean HUI-derived utility at between -0.02 and 0.96. CONCLUSIONS: The results from this pilot study show that German children with SMA, despite significant physical disability, have surprisingly good HRQoL as assessed using KIDSCREEN-27. Yet, many reside in health states associated with low utility. The disease burden was generally higher among non-sitters compared with walkers, and SMA type I compared with type III, but more research is needed to further delineate this variability. Our preliminary findings contribute to the understanding of HRQoL in pediatric patients with SMA and should be helpful to inform the design of future studies of this patient population.

Prenatal stress and child externalizing behavior: effects of maternal perceived stress and cortisol are moderated by child sex.

BACKGROUND: Externalizing behavior problems are related to social maladjustment. Evidence indicates associations between prenatal stress and child behavioral outcomes. It remains unclear how psychological distress vs. biological correlates of stress (cortisol) differentially predict externalizing behavior, and how their effects might differ as a function of child sex. METHOD: 108 pregnant women from the community collected salivary cortisol and reported their perceived stress during each trimester of pregnancy. At child age 9 years (M = 9.01, SD = 0.55), 70 mothers and children reported on child behavior. Structural equation modelling was used to analyze how cortisol levels and perceived stress during pregnancy predicted current child externalizing behavior, considering the moderating effect of child sex. RESULTS: Perceived stress predicted higher externalizing behavior in boys (ß = 0.42, p = 0.009) and lower externalizing behavior in girls (ß = - 0.56, p = 0.014). Cortisol predicted lower externalizing behavior in boys (ß = - 0.81, p < .001) and was not related to girls' externalizing behavior (ß = 0.37, p = 0.200). DISCUSSION/CONCLUSION: Prenatal stress affected externalizing behavior differently in girls vs. boys. These response patters in turn differed for indicators of psychological vs. biological maternal stress, encouraging an integrated approach. Findings indicate that perceived stress and cortisol may affect child development via different trajectories.

Areas of improvement in the medical care of SMA: evidence from a nationwide patient registry in Germany.

BACKGROUND: Management and treatment of spinal muscular atrophy (SMA) has changed in recent years due to the introduction of novel transformative and potentially curative therapies resulting in the emergence of new disease phenotypes. Yet, little is known about the uptake and impact of these therapies in real-world clinical practice. The objective of this study was to describe current motor function, need of assistive devices, and therapeutic and supportive interventions provided by the healthcare system, as well as the socioeconomic situation of children and adults with different SMA phenotypes in Germany. We conducted a cross-sectional, observational study of German patients with genetically confirmed SMA identified and recruited via a nationwide SMA patient registry ( www.sma-register.de ) within the TREAT-NMD network. Study data was recorded directly from patient-caregiver pairs through a study questionnaire administered online via a dedicated study website. RESULTS: The final study cohort consisted of 107 patients with SMA. Of these, 24 were children and 83 adults. In total, about 78% of all participants were taking medication for SMA (predominantly nusinersen and risdiplam). All children with SMA1 were able to sit and 27% of children with SMA2 were able to stand or walk. Impaired upper limb function, scoliosis and bulbar dysfunction were observed more frequently in patients with reduced lower limb performance. Physiotherapy, occupational therapy, and speech therapy, as well as the use of cough assists were less common than indicated by care guidelines. Family planning and educational and employment status appear to be related to motor skill impairment. CONCLUSIONS: We show that the natural history of disease has changed in Germany following improvements in SMA care and the introduction of novel therapies. Yet, a non-trivial proportion of patients remain untreated. We also identified considerable limitations in rehabilitation and respiratory care, as well as low labour-market participation among adults with SMA, calling for action to improve the current situation.

Child versus adolescent borderline personality disorder traits: Frequency, psychosocial correlates, and observed mother-child interactions.

Research has established the diagnostic validity of borderline personality disorder (BPD) in adolescence. The roots of BPD often lie in childhood; however, significantly less is known about the presence and correlates of BPD traits in school-age children and whether these are comparable with those observed in adolescents. Trained psychologists administered the Childhood Interview for Borderline Personality Disorder in a cohort of 14-year-old adolescents (n = 76) and a cohort of 9-year-old children (n = 70). We compared the prevalence of BPD traits in both cohorts and investigated common psychosocial correlates (comorbidity, impaired quality of life, emotional/behavioral problems, maternal distress, and observed mother-child interaction). Children and adolescents showed no significant differences regarding the type and frequency of BPD traits. In both cohorts, BPD traits were associated with comorbidity, emotional and behavioral problems, and lower quality of life. In contrast to adolescents, children's BPD traits were not significantly related to maternal distress and showed less relations to interaction patterns. Negative maternal and dyadic behavior were associated with more BPD traits in adolescents during a conflict discussion but not during fun day planning. Our study suggests that BPD traits in children are similarly frequent as in adolescents and accompanied by psychosocial impairment. However, age-related differences were revealed, mostly indicating weaker associations with the mother-child relationship. Mother-child interaction patterns in youth seem to be especially relevant during conflict discussion and provide a target for intervention. Our study provides preliminary support for potential early detection of BPD pathology among children and encourages further study of its life span perspective. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Dissociation Links Maternal History Of Childhood Abuse To Impaired parenting.

The present study investigated dissociation as a predictor of parenting and a potential mediator in the relationship between early life maltreatment (ELM) and impaired parenting. Mothers reporting moderate to severe sexual and/or physical abuse (assessed with the Childhood Trauma Questionnaire) formed the maltreatment group (n = 58; MG) and were compared to a non-maltreated comparison group (n = 61; CG) 5 months (T1) and 12 months (T2) postpartum. Dissociative symptoms were assessed with the Dissociative Experiences Scale (DES) at T1. Parenting was investigated by self-report questionnaires and behavior observation (Emotional Availability Scales; EA) at T2. Higher dissociation scores significantly predicted more self-reported parental bonding impairment and stress, higher physical abuse risk and less observed maternal sensitivity, non-intrusiveness and a lower total EA-score during mother-child interactions (p < .001 to p < .05). Dissociation mediated the associations between ELM and self-reported parenting, but not the associations between ELM and parenting as observed during mother-child interactions. Our results suggest that maternal dissociative symptoms play a distinct role in the intergenerational transmission of adverse childhood experiences and should therefore be targeted in therapeutic interventions provided for victims of physical/sexual childhood abuse and in preventive family programs.

Early Parenting Stress Links Obstetric Complications and Child Psychopathology in Middle Childhood in an At-Risk Sample.

OBJECTIVE: Obstetric complications (OCs) are adverse events during pregnancy, birth, or immediately after birth. Evidence on cumulative OC and longitudinal associations with child psychopathology is sparse. Prospective studies testing mediating pathways such as parenting stress are needed. This study aimed to investigate the impact of OC on child psychopathology in middle childhood and to highlight whether and which type of parenting stress specifically mediates this association. METHODS: We investigated n = 54 mother-child dyads from 5 months to 8 years of age. Child psychopathology at 8 years and parenting stress at 12 months were assessed using the Child Behavior Checklist (CBCL) and the Parenting Stress Index. OCs were evaluated by the Steinhausen Questionnaire and through access to official pregnancy records at the 5-month visit. Half of the mothers had experienced early-life maltreatment (ELM), assessed with the Childhood Trauma Questionnaire. RESULTS: There was a significant indirect effect of maternal parenting stress at 12 months mediating the association between OC and child psychopathology at 8 years (ß = 0.26; p < 0.01; 95% [0.35-1.83]). A significant proportion of 35% of CBCL-variance was explained. The significant effect remained even when maternal ELM and maternal psychological distress were controlled for. On the subscale level, only the "Difficult Child" subscale was a significant mediator. CONCLUSION: Our findings suggest that parenting stress should be targeted to prevent adverse effects of OC on child psychopathology. More research focusing on families subjected to OC is needed to highlight how maternal parenting stress and child regulatory functioning interact to affect child development longitudinally.

Maternal bonding impairment predicts personality disorder features in adolescence: The moderating role of child temperament and sex.

Research has shown associations between adverse parenting experiences and (borderline) personality disorder ([B]PD). A biopsychosocial model suggests that child characteristics and the environment interact in the development of symptoms. However, prospective data in this aspect are limited. This study focused on maternal bonding impairment (MBI; 2 weeks postpartum) and its interactions with child temperament (age 5) and child sex as predictors of BPD symptoms and general personality dysfunction in adolescence. Participants were 64 mother-child dyads from a community sample who took part in a 14-year longitudinal study. Higher MBI was a significant predictor of general personality dysfunction as defined in Criterion A of the alternative model for PD of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Interactions showed that the effect of MBI on general personality dysfunction was decreased for children higher in harm avoidance and increased for children higher in novelty seeking. There was also a negative main effect of harm avoidance on (B)PD features. Regarding BPD symptoms, the MBI × Child Sex interaction indicated differential susceptibility. Girls' but not boys' BPD symptoms were dependent on maternal bonding. Our results indicate that children at risk of developing personality pathology can be identified early in life. They stress the importance of early relationship disturbances in the development of personality pathology and refine the understanding of differential susceptibility factors in the context of MBI and PD symptom development. Our findings can be applied to target at-risk dyads for selective early prevention based on temperament and maternal bonding. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Neural processing of the own child's facial emotions in mothers with a history of early life maltreatment.

Early life maltreatment (ELM) has long-lasting effects on social interaction. When interacting with their own child, women with ELM often report difficulties in parenting and show reduced maternal sensitivity. Sensitive maternal behavior requires the recognition of the child's emotional state depicted in its facial emotions. Based on previous studies, it can be expected that ELM affects the neural processing of facial emotions by altering activation patterns in parts of the brain's empathy and mentalizing networks. However, so far studies have focused on the processing of standardized, adult facial emotions. Therefore, the current study investigated the impact of ELM on the processing of one's own child's facial emotions using functional magnetic resonance imaging. To achieve this, 27 mothers with and 26 mothers without a history of ELM (all without current mental disorders and psychopharmacological treatment) took part in an emotional face recognition paradigm with happy, sad, and neutral faces of their own and an unknown primary school-aged child of the same age and sex. We found elevated activations in regions of the mentalizing (superior temporal sulcus, precuneus) and mirror neuron (inferior parietal lobule) networks as well as in the visual face processing network (cuneus, middle temporal gyrus) in mothers with ELM compared to the non-maltreated mothers in response to happy faces of their own child. This suggests a more effortful processing and cognitive empathic mentalizing of the own child's facial happiness in mothers with ELM. Future research should address whether this might indicate a compensatory recruitment of mentalizing capacities to maintain maternal sensitivity.

The maternal brain in women with a history of early-life maltreatment: an imagination-based fMRI study of conflictual versus pleasant interactions with children.

BACKGROUND: Early-life maltreatment has severe consequences for the affected individual, and it has an impact on the next generation. To improve understanding of the intergenerational effects of abuse, we investigated the consequences of early-life maltreatment on maternal sensitivity and associated brain mechanisms during mother-child interactions. METHODS: In total, 47 mothers (22 with a history of physical and/or sexual childhood abuse and 25 without, all without current mental disorders) took part in a standardized real-life interaction with their 7- to 11-year-old child (not abused) and a subsequent functional imaging script-driven imagery task. RESULTS: Mothers with early-life maltreatment were less sensitive in real-life mother-child interactions, but while imagining conflictual interactions with their child, they showed increased activation in regions of the salience and emotion-processing network, such as the amygdala, insula and hippocampus. This activation pattern was in contrast to that of mothers without early-life maltreatment, who showed higher activations in those regions in response to pleasant mother-child interactions. Mothers with early-life maltreatment also showed reduced functional connectivity between regions of the salience and the mentalizing networks. LIMITATIONS: Region-of-interest analyses, which were performed in addition to whole-brain analyses, were exploratory in nature, because they were not further controlled for multiple comparisons. CONCLUSION: Results suggest that for mothers with early-life maltreatment, conflictual interactions with their child may be more salient and behaviourally relevant than pleasant interactions, and that their salience network is poorly modulated by the brain regions involved in mentalizing processes. This activation pattern offers new insights into the mechanisms behind the intergenerational effects of maltreatment and into options for reducing these effects.

The effect of a maternal history of childhood abuse on adrenocortical attunement in mothers and their toddlers.

We investigated circadian mother-child adrenocortical attunement in the context of a maternal history of childhood abuse (HoA). Mothers were screened after birth using the Childhood Trauma Questionnaire. Women reporting moderate or severe abuse formed the HoA group (n = 37; HoAG) and were compared with a non-maltreated comparison group (n = 45; CG). Three years later, cortisol awakening response (CAR) and diurnal slope (DSL) were assessed. Mother-child interaction was coded using the Emotional Availability Scales at 12 months of age. For the CAR, we found adrenocortical attunement only in the HoAG (2-way interaction: p = .004), particularly if mothers scored low on structuring (3-way interaction: p = .042) and children scored low on responsiveness (3-way interaction: p = .044). DSL-attunement was dependent on maternal sensitivity (3-way interaction: p = .012) and child involvement (3-way interaction: p = .012). In the context of a maternal HoA, it seems possible for mother-child-dyads to show less optimal interactional quality but be stronger attuned to each other biologically.

Prenatal stress and infant affective reactivity at five months of age.

BACKGROUND: prospective studies concerning prenatal stress and its outcome on children's emotional development postulated a potential influence of prenatal hormonal levels or emotional stressors on child development [1-3]. In a retrospective study, an influence of maternal emotional stress on infant affective reactivity was found [4]. AIMS: this study was conducted in order to confirm these findings in a prospective study design. STUDY DESIGN: a prospective longitudinal study design was conducted with three study waves during pregnancy and one time point five months postnatally. SUBJECTS: the final sample consisted of n=104 mother-infant dyads. OUTCOME MEASURES: Maternal baseline cortisol levels and emotional stress were assessed in each trimester of pregnancy. Children were examined with the infant reactivity battery according to Kagan & Snidman [5] at the age of five months. RESULTS: mothers of children with high affective reactivity (cry score≥7) were significantly less depressed (p<.10) and perceived less stress (p<.05) in mid-pregnancy and were confronted with less external stress factors (p<.10) at the end of pregnancy. Cortisol levels did not differ in both groups in any pregnancy trimenon (p>.05). CONCLUSIONS: these data add a new specific aspect to the 'fetal programming hypothesis' and are the first to confirm the speculative data from retrospective studies. Baseline cortisol does not seem to be the 'hormonal mediator' of this association. Therefore, cortisol stress reactivity or other neuroendocrine mechanisms should be assessed in future studies.

Prenatal stress: course and interrelation of emotional and physiological stress measures.

BACKGROUND: Prenatal stress is known to be a potential risk factor for cognitive, behavioural and motor development that even last until adolescence. A consensus of how 'prenatal stress' can be measured, in which trimester of pregnancy women should be studied and whether subjective feelings of being stressed are associated with a hormonal response is still lacking. To close this gap, a prospective longitudinal study was conducted in pregnant women. SAMPLING AND METHODS: 108 subjects were asked to fill out questionnaires concerning pregnancy-related anxiety, perceived stress, marital satisfaction, critical life events and to collect salivary cortisol in each trimester of pregnancy. RESULTS: Fear of giving birth increases until the end of pregnancy, and marital satisfaction is highest at the end of pregnancy. Perceived stress is related to a hormonal response in cortisol only in the first (r = 0.18, p < 0.10) and second (r = 0.18, p < 0.10) trimesters of pregnancy. Critical life events are linked to raised cortisol levels in early pregnancy only (r = 0.28, p < 0.01). CONCLUSION: Prenatal stress can be operationalized by using different subjective as well as physiological stress measures. Only in the first half of pregnancy self-report and physiological stress measures seem to be associated.

History of childhood abuse is accompanied by increased dissociation in young mothers five months postnatally.

BACKGROUND: Dissociation has been recognized as a relevant factor within the context of traumatization. Since childhood maltreatment as well as child birth can be regarded as a potential trauma, this study examined dissociation in a sample of 58 young mothers with a history of abuse in comparison to a control group. METHODS: All women with newborn children were contacted by mail and presented with the Childhood Trauma Questionnaire. Women who reached a cutoff for moderate or severe sexual and/or physical abuse and whose children were term babies with Apgar scores >7 were included in the study to form the index group (n = 58); the control group was formed by matching mothers with no reported experiences of physical and/or sexual abuse (n = 61). Dissociative experiences were assessed by the Scale of Dissociative Experiences (German version of the Dissociative Experiences Scale). RESULTS: The results show that mothers with a history of physical or sexual abuse - matched for infant gender, maternal education, marital status, number of infants and birth weight - had significantly more dissociative experiences. CONCLUSIONS: Maternal history of abuse significantly increases maternal dissociative experiences, which has frequently been postulated but never empirically shown in a prospective design in a sample of young mothers. As maternal psychopathology has been found to have a profound impact on child development, specifically in the first year of life, these data are of immediate relevance for preventive efforts when targeting at-risk mother-infant dyads.

Can Mothers Predict Childhood Behavioural Inhibition in Early Infancy?

BACKGROUND: Focusing on early identification of developmental risk factors, this study examined the question whether maternal report of child behaviour during early infancy is related to a laboratory measure of behavioural inhibition at 14 months of age. METHOD: A sample of 101 mother-infant pairs was recruited from local obstetric units. The Infant Behaviour Questionnaire (IBQ) was presented at 4 months postnatal age. Child behavioural inhibition was assessed at 14 months in a laboratory procedure. RESULTS: Infant distress to novelty as measured by the IBQ at 4 months postnatal age was found to be associated with toddler's fear score/behavioural inhibition at 14 months (p = .003). Distress-to-limitations subscore, smile/laughter subscore, activity subscore, and soothability subscore of the IBQ showed no correlation with behavioural inhibition. CONCLUSIONS: Behavioural inhibition, as a potential risk factor for childhood shyness and anxiety, can be predicted by maternal judgment of infant distress to novelty at age 4 months. The Infant Behaviour Questionnaire therefore might be used to identify infants presumably at risk for childhood anxiety disorders.

Vacuum extraction and autonomic balance in human infants.

The impact of delivery mode on the cardiac autonomic balance was studied in a sample of 101 full term appropriate for gestational age (AGA) human infants. Cardiac autonomic balance was measured by assessing basic heart rate, and two indicators of vagal tone, the Root Mean Square of Successive Differences (RMSSD) and Standard Deviation of NN-intervals (SDNN) as two different measures of short-term heart rate variability at 2, 6, and 16 weeks postnatal age. Sixty-seven infants were delivered spontaneously, 29 by cesarean section and five by vacuum extraction. Children delivered by vacuum extraction had a significantly lower basic heart rate (P=0.01), higher RMSSD (P=0.0003) and higher SDNN (P=0.0001) at two, but not at six and sixteen weeks, indicating a temporary elevation of cardiac vagal tone in these infants. These data indicate a potential transitory impact of vacuum extraction on autonomic balance persisting until at least two weeks postnatal age.

Emotional availability in a sample of mothers with a history of abuse.

Maternal history of abuse has been proposed as a risk factor for child maltreatment, but the background of this "cycle of abuse" is as yet poorly understood. As a contribution toward a deeper understanding of this phenomenon, this study analyzed whether emotional availability is altered by maternal experiences of physical or sexual abuse during their upbringing. Mothers were contacted by mail and presented with the Childhood Trauma Questionnaire. To form the index group, women who reached a cutoff for severe sexual and/or physical abuse and whose children were term babies with APGAR scores 7 were included in the study. The women were invited to the laboratory when their infants were 5 months old. Emotional availability was compared with a group of mother-infant pairs matched for infant gender, maternal education, marital status, number of infants, and birth weight. The results show that 5-month postnatal mothers with a history of physical or sexual abuse were significantly more intrusive toward their children than were control mothers.

Association of behavioral inhibition with hair pigmentation in a European sample.

Behavioral inhibition, a temperamental trait signalling a predisposition to childhood and adolescent anxiety disorders, is slightly more frequent in America among Caucasian children having blue irises. This paper examines a community sample of 101 German toddlers assessed for behavioral inhibition in a standardized laboratory procedure. Hair pigmentation was found to be significantly associated with behavioral inhibition in the sense that blond children exhibited higher fear scores. As in American samples, blue-eyed children had a higher fear score than did other children, but this difference was not statistically significant.