Dealing With Autocorrelation in the Single Case AB-Design: A Study Assessing the Mediating Effect of Infant Crying on the Relation Between Responsive Soothing and Infant Sleep.

Mediation analysis is widely adopted by researchers to disentangle the causal pathways by which an intervention affects an outcome. This paper describes a model to estimate the direct and indirect effect from a single subject AB-design with repeated assessments of both the mediator and the outcome. We discuss the plausibility of the modeling assumptions and contrast different approaches to deal with the autocorrelation in the time series data. While there are only small differences between those approaches when the number of timepoints is small (T = 15), the Generalized Least Squares approach performs best in medium (T = 30) to large (T = 90) time series. We apply the proposed methodology to data from a single case AB-design that was conducted with a mother of an excessively crying baby. Daily crying and baby sleep during the night were assessed with online diaries during a baseline phase and intervention phase. Between both phases, the pediatrician instructed the mother how to apply a responsive soothing intervention, the happiest baby (THB) method. We find that the direct effect of THB on sleeping is positive. THB also reduces crying but decreased crying during the day is associated with decreased sleeping during the night and hence a negative indirect effect of THB on sleeping via crying is found.

Well-being of mothers with epilepsy with school-aged children.

PURPOSE: The purpose of the study was to examine different aspects of well-being in mothers with epilepsy with school-aged children. METHODS: In an observational study, mothers, identified from the European Registry of Antiepileptic Drugs and Pregnancy database in the Netherlands, completed questions on epilepsy, the impact of epilepsy on daily functioning, quality of life, behavioral problems, and parenting stress. Descriptive analyses were performed to examine the prevalence of behavioral problems and the impact of epilepsy on different aspects of the mother's daily functioning and family life. We subsequently investigated which factors contributed most to the impact of maternal epilepsy using regression analyses. RESULTS: One hundred fifty-six (46%) of the 342 invited mothers with epilepsy participated. The majority (89%) had low epilepsy severity, with well-controlled seizures. Internalizing problems within the borderline or clinical range were reported by 23% of the mothers. Behavioral problems were significantly correlated with epilepsy severity (r = 0.26, p = .002), impact of epilepsy on daily functioning (r = 0.32, p < .001), and quality of life (r = -0.52, p < 01). Quality of life was in general good (mean = 8, standard deviation [SD] = 1), with low impact of epilepsy. Epilepsy affected mostly maternal self-confidence, work, and general health. Mothers indicated to experience no to little impact of epilepsy on the relationship with their children, partner, or family. Regression analyses showed that epilepsy severity (1.0, 95% confidence interval [CI]: 0.4 to 1.6; p = .002) and quality of life (-1.3, CI: -2.3 to -0.4; p = .007) were significant contributors to the impact of epilepsy on daily functioning, while other factors (maternal education, family type, behavioral problems, and parenting stress) were nonsignificant. DISCUSSION: The current study shows that mothers with epilepsy generally fared well. Epilepsy negatively impacted the lives of some mothers, though. As maternal well-being is of importance for mother-child interaction and child development, clinicians should be aware of the impact of epilepsy on maternal psychosocial outcomes and family life of women with epilepsy.

Neurocognition after prenatal levetiracetam, lamotrigine, carbamazepine or valproate exposure.

OBJECTIVE: To examine neurocognitive functioning of children exposed prenatally to carbamazepine, lamotrigine, levetiracetam or valproate monotherapy. METHODS: In a prospective observational study, children aged 6 or 7 years, identified from the European Registry of Antiepileptic Drugs and Pregnancy database in The Netherlands, were assessed using the Wechsler Intelligence Scale for Children and the developmental neuropsychological assessment. Maternal IQ was measured using Wechsler Adult Intelligence Scale. Assessors were blinded to drug exposures. RESULTS: One hundred and sixty-one children (one set of twins and 21 sibling pairs) of 139 mothers were included. As a group, children achieved average scores on neurocognitive outcomes. Children exposed to valproate (n = 22) performed lower on all six neurocognitive domains, especially language, than those exposed to carbamazepine (n = 32), lamotrigine (n = 82) or levetiracetam (n = 25). After controlling for maternal IQ and drug dose, the verbal IQ of valproate-exposed children was on average 9.1 points lower than those exposed to carbamazepine (95% confidence interval [CI] 1.3-17.0; p = 0.023), 10.3 lower than lamotrigine-exposed children (CI 3.4-17.3; p = 0.004) and 13.4 lower than levetiracetam-exposed children (CI 5.2-21.6; p = 0.002). No significant dose-effect was found. Virtually no significant differences were found between lamotrigine and levetiracetam or lamotrigine and carbamazepine exposed children. CONCLUSIONS: Consistent with previous research, valproate-exposed children experienced more problems compared to three other common antiepileptic drugs, while children exposed to lamotrigine, carbamazepine or levetiracetam revealed little to no problems. This illustrates the need for systematic follow-up of prenatally exposed children, to support pre-pregnancy counseling and treatment decisions in women of reproductive age.

The Relation Between Attachment and Depression in Children and Adolescents: A Multilevel Meta-Analysis.

Insecure attachment to primary caregivers is associated with the development of depression symptoms in children and youth. This association has been shown by individual studies testing the relation between attachment and depression and by meta-analyses focusing on broad internalizing problems instead of depression or adult samples only. We therefore meta-analytically examined the associations between attachment security and depression in children and adolescents, using a multilevel approach. In total, 643 effect sizes were extracted from 123 independent samples. A significant moderate overall effect size was found (r = .31), indicating that insecure attachment to primary caregivers is associated with depression. Multivariate analysis of the significant moderators that impacted on the strength of the association between attachment security and depression showed that country of the study, study design, gender, the type of attachment, and the type of instrument to assess attachment uniquely contributed to the explanation of variance. This study suggests that insecure attachment may be a predictor of the development of depression in children and adolescents. When treating depression in children, attachment should therefore be addressed.

Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy.

OBJECTIVE: To examine the behavioral functioning of children prenatally exposed to carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or valproate (VPA) monotherapy. METHODS: In collaboration with the European Registry of Antiepileptic Drugs and Pregnancy (EURAP), the Dutch EURAP & Development study was designed, a prospective observational study. Between January 2015 and March 2018, the Child Behavior Checklist and the Social Emotional Questionnaire were used to examine the nature and severity of behavioral problems. VPA-exposed children were compared to children exposed to CBZ, LTG, or LEV, taking potential confounders into account. A direct comparison was also made between LTG and LEV, as these are first-choice treatments for many women with epilepsy of childbearing potential. RESULTS: Of the 405 invited, 181 children were included; 26 were exposed to VPA, 37 to CBZ, 88 to LTG, and 30 to LEV. For most children, both parents completed the behavioral questionnaires. Across all four antiepileptic drug (AED) exposure groups, high percentages of children with clinically relevant behavior problems were found, with behavioral problems occurring in 32% of VPA-exposed children, 14% of CBZ, 16% of LTG, and 14% of LEV. After controlling for potential confounders, VPA-exposed children had significantly more social problems than those exposed to LTG (-2.8, 95% confidence interval [CI] = -5.2 to -0.4; P = 0.022) or LEV (-3.2, CI: -6.1 to -0.3; P = 0.028), and significantly more attention problems than LEV-exposed children (-3.7, CI: -6.7 to -0.8; P = 0.013). LTG-exposed children had significantly more attention deficit (-9.2, CI: -17.3 to 1.1; P = 0.026), but significantly less anxious behavior when compared to LEV-exposed children (9.0, CI: 0.3-17.6; P = 0.042). SIGNIFICANCE: Compared to population norms, a high proportion of children of mothers with epilepsy exposed prenatally to monotherapy with four common AEDs had clinical behavioral problems reported by parents. Different patterns were seen, with some but not all subscales raised for all AED exposure groups. It is important that prenatally AED-exposed children are regularly screened for behavioral problems so that appropriate help can be provided.

Maternal epilepsy and behavioral development of the child: Family factors do matter.

PURPOSE: The purpose of the study was to examine whether mothers with epilepsy experience family problems and to investigate the possible mediating role of distinct family factors in the relationship between maternal epilepsy and child behavioral problems, in which it is also investigated whether more proximal family factors mediate the more distal family factors. METHODS: In an observational study, with children identified from the European Registry of Antiepileptic Drugs and Pregnancy database in the Netherlands (EURAP-NL), parents completed questionnaires on maternal epilepsy, family factors (proximal, distal, contextual, global), and child behavior. Hierarchical multilevel regression analyses were performed to examine the relative contribution of epilepsy-related and family factors on child internalizing and externalizing problems. RESULTS: Between January 2015 and March 2018, the questionnaires were completed for 175 children. Mothers with epilepsy showed significantly more parenting stress and problems with parenting than mothers from the general population. Family factors were significantly associated with child behavioral problems. For internalizing problems, maternal epilepsy, global, contextual, and distal family factors were each found to have significant added value. Distal family factors contributed most to internalizing problems and showed a mediating role for epilepsy-related factors and previous added family factors in the model. Global, contextual, distal, and proximal factors were all found to be significant contributors to externalizing problems, with the factor most proximal to the child (quality of parent-child interaction) showing the largest effect. DISCUSSION: Including family factors in research regarding children of mothers with epilepsy is important as they can have a contribution additional to the teratogenic risks of prenatal exposure to antiepileptic drugs (AEDs). Family factors, in particular distal and proximal family factors, can weaken or strengthen child development and may provide starting points for interventions.

Infant crying and the calming response: Parental versus mechanical soothing using swaddling, sound, and movement.

BACKGROUND: Frequent infant crying is associated with parental exhaustion, depression, or even infant hospitalization and shaken baby syndrome. Effective prompt soothing methods are lacking for infants under 6 months. We examined whether swaddling, sound, and movement evoked an immediate calming response (CR) when parents soothed their infants and using a smart crib, and whether infant age affected the CR. METHODS: Infants' CR was assessed in a community sample of 69 infants (0-6 months) in a counterbalanced experiment with two conditions (parent, smart crib) each composed of three two-minute phases (baseline, supine, soothing). During baseline 1, parent and infant were sitting together; in supine 1, fussiness was elicited by putting the infant suddenly supine, followed by parental soothing (shushing and jiggling of the swaddled infant). Baseline 2, supine 2, and soothing by the crib followed. Fussiness was observed and infant heart rate (HR) and heart rate variability (HRV) were recorded. The CR was operationalized as decreased fussiness and HR, and increased HRV during soothing compared to lying supine. RESULTS: Infant fussiness and HR were lower in both soothing phases compared to the supine phases. Infant HRV tended to be higher during parental soothing than during supine, but did not significantly differ between mechanical soothing and supine. Younger infants responded with a stronger CR (decreased fussiness and increased HRV) to parental soothing, but not to mechanical soothing. For HR, infants' CR was stronger in the crib than in the parent condition, whereas for HRV, infants' CR was stronger in the parent condition. For fussiness, infants' CR tended to be stronger in the parent condition. CONCLUSION: Parental and mechanical soothing using swaddling, sound, and movement promptly induced a CR in infants. This has important clinical implications for soothing fussy and crying infants. Future studies should investigate the effects of parental versus mechanical soothing in the home setting.

Exposure to antiepileptic drugs in pregnancy: The need for a family factor framework.

PURPOSE: Children exposed to antiepileptic drugs (AEDs) in utero are at risk for developmental problems. Maternal epilepsy, its impact on the family system, and other family factors may also contribute. We reviewed the possible associations between family factors and developmental outcome in children who had been exposed to AED during pregnancy. METHODS: We conducted a narrative review and searched MEDLINE, Embase, Google Scholar, and PsycINFO on the following terms: in utero exposure, pregnancy outcome, and AEDs. A family factor framework (the ABCX model) served as the basis to review distinct family factors in children who were exposed to AEDs in pregnancy. RESULTS: Few studies have investigated these factors. Mothers with epilepsy have problems caring for themselves and for the child and experience more parenting stress. There is a paucity of studies of the possible impact of family factors on the neurocognitive and behavioral development of children of mothers with epilepsy. DISCUSSION: Further work is required to ascertain which family factors are associated with child development in addition to the effects of AED exposure and their potential interaction. As epilepsy may have considerable impact on intrafamily factors and as children are especially vulnerable to such effects, study designs incorporating family factors should be encouraged.

Pediatric seizure-related posttraumatic stress and anxiety symptoms treated with EMDR: a case series.

PURPOSE: To examine the potential effects of eye movement desensitization and reprocessing (EMDR) in children with epilepsy-related posttraumatic stress and/or anxiety symptoms, using a case series design. METHODS: Five children (aged 8-18) with epilepsy identified for seizure-related posttraumatic stress and/or anxiety symptoms were treated with EMDR. To examine potential treatment effects, posttraumatic stress and anxiety symptoms were assessed (CRTI and SCARED) pre- and post-EMDR and at 3-month follow-up. Normative deviation scores were calculated to examine the severity of seizure-related posttraumatic stress and anxiety symptoms over time. The reliable change index was calculated for pre- to posttreatment change of seizure-related posttraumatic stress and/or anxiety symptoms. RESULTS: Before EMDR, overall or subscale scores indicated that all children had (sub)clinical seizure-related posttraumatic stress symptoms and/or anxiety symptoms. Directly after EMDR, most children showed significant and/or clinical individual improvement, and these beneficial effects were maintained or reached at follow-up. The mean number of sessions was 2 (range 1-3, 45 min per session). CONCLUSIONS: In case of seizure-related posttraumatic stress and/or anxiety, this study indicates that EMDR is a potentially successful quick and safe psychological treatment for children with epilepsy.

Parenting and restrictions in childhood epilepsy.

PURPOSE: From the overprotection literature, the predictive and interactional (moderation) effects of controlling and indulgent parenting on restrictions in children with epilepsy were examined. METHODS: Parents of 73 children with epilepsy completed questionnaires on parenting, restrictions, and functional status. Predictive and moderation effects were tested using multiple regression analysis. Moderation was tested with interactive computational methods. RESULTS: Restrictions were significantly (R(2)=.38, FΔ=6.59***, p<.001) predicted from seizure frequency (ß=.24*, p<.05), functional status (ß=-.42***, p<.001), and interaction between controlling and indulgent parenting (ß=.28**, p<.01). Moderation occurred predominantly for high values of control: controlling parents who were not indulgent imposed fewer restrictions. In contrast, controlling parents who were indulgent imposed more restrictions. CONCLUSION: Parents who were controlling and more indulgent imposed more restrictions. Clinicians should ask parents about parenting and restrictions. Future research should examine whether the current study's findings can be replicated.

Sleep in children with asthma: results of the PIAMA study.

Children with asthma are thought to have impaired sleep quality and quantity. In this study, we investigated which of the many sleep aspects are associated with asthma. Our sample consisted of 2529 children (aged 11 years) who participated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study. Parents reported about asthma symptoms (wheezing, dyspnoea, prescription of inhaled corticosteroids and asthma diagnosis) and children reported about different aspects of sleep (bedtime, rise time, sleep quality and daytime sleepiness/tiredness). Results were analysed with (logistic) regression analysis. Children with frequent asthma symptoms significantly more often reported that they felt sleepy or tired during the day (34.4% experienced daytime sleepiness/tiredness at least once a week) than children without asthma symptoms (22.2%) and children with infrequent asthma symptoms (21.9%). This association was not confounded by sex, age of the child, parental educational level or smoking inside the house; the effect was also not modified by sex. There were no associations between asthma and bedtime, time spent in bed or sleep quality. Children with frequent asthma symptoms experienced daytime sleepiness/tiredness more often than children with infrequent or no asthma symptoms. Otherwise, children with asthma did not differ much from children without asthma with regard to sleep.

Psychosocial issues for children with epilepsy.

Epilepsy is a pervasive disorder that consists not only of seizures, but of behavioral, academic, and social difficulties. Epilepsy has an impact on the entire family and may have a significant effect on the interrelationships between child and parent. Epilepsy also has a potentially deleterious effect on academic functioning that may be the result of central nervous system dysfunction, seizures, antiepileptic drugs, or child and family response to illness. Early assessment for psychosocial problems and appropriate interventions can be beneficial for the child and family. Particular attention should be paid to periods of transition such as the move from adolescence to adulthood.

Eye movement desensitization and reprocessing in an adolescent with epilepsy and mild intellectual disability.

Intellectual disability is a comorbid condition in epilepsy. People with epilepsy and intellectual disability are at high risk of developing behavioral problems. Among the many contributors to behavioral problems in people with epilepsy and intellectual disability are those of traumatic experiences. As such, behavioral problems can be seen as a reflection of these traumatic experiences. Among established trauma therapies, eye movement desensitization and reprocessing (EMDR) is an emerging treatment that is effective in adults and also seems to be effective in children. This article is a case report of EMDR in an adolescent with epilepsy and mild intellectual disability, in whom the EMDR children's protocol was used. The aim was to assess whether clinical trauma status significantly diminished to nonclinical status posttreatment. Change in trauma symptoms was evaluated with the Reliable Change Index (RCI). Results showed a significant decrease in trauma symptoms toward nonclinical status from pretreatment to posttreatment. EMDR consequences for epilepsy and intellectual disability are discussed.

Efficacy of EMDR in children: a meta-analysis.

The efficacy of eye movement desensitization and reprocessing (EMDR) in children with post-traumatic stress symptoms was meta-analytically examined from the perspective of incremental efficacy. Overall post-treatment effect size for EMDR was medium and significant (d=.56). Results indicate efficacy of EMDR when effect sizes are based on comparisons between the EMDR and the non-established trauma treatment or the no-treatment control groups, and the incremental efficacy when effect sizes are based on comparisons between the EMDR and the established (CBT) trauma treatment. The discussion focuses on the future replication of EMDR findings and further research on post-traumatic stress in children.

Parents of children with enduring epilepsy: predictors of parenting stress and parenting.

OBJECTIVE: The goals of the work described here were (1) to predict parenting stress and parenting from stressors, resources, and parental coping behaviors in parents of children with epilepsy, and (2) to determine whether parenting stress mediates the effects of these predictors on parenting. METHODS: Participants were 91 parents of children with epilepsy (mean age of children=8 years, 5 months). Parental perceptions of stressors, resources, parental coping behaviors, parenting stress, and parenting were assessed by means of questionnaires. Regression analyses were used to analyze the unique and combined power of the predictors to predict parenting stress and parenting. Sobel tests were used to identify the mediational role of parenting stress. RESULTS: Evidence was found for direct effects of stressors, resources, and coping behaviors on parenting stress and parenting, with relatively large effects for stressors. The mediational role of parenting stress was largest in the domain of parental behavioral control. CONCLUSIONS: In the context of pediatric epilepsy, parenting stress mediates both disruptive and resilient family factors for their effects on parenting. Parents of children with epilepsy may benefit from parent training programs that, to reduce parenting stress, address epilepsy education, the management of difficult child temperament, building social support networks, and the modification of inadequate parental coping behaviors.

Family predictors of psychopathology in children with epilepsy.

PURPOSE: To examine the contribution of epilepsy-related factors, proximal (parent-child relationship quality), distal (parental characteristics), and contextual (quality of other family relationships) family factors to psychopathology (both broad-band and narrow-band syndromes) in children with epilepsy and normal intelligence. METHODS: Parents of 91 children (mean, 8.5 years) participated by filling out questionnaires about family factors and child psychopathology. Regression analyses were used to analyze the unique and combined predictive power of family factors in relation to psychopathology. RESULTS: In contrast to epilepsy-related factors, family factors, especially those related to the quality of the parent-child relationship, appeared to be strong predictors of psychopathology. The results supported the mediational model: Distal and contextual factors affect child psychopathology by affecting proximal factors. CONCLUSIONS: In treating children with epilepsy, clinicians should be aware of the importance of the parent-child relationship quality. Strengthening the relationship quality may prevent or reduce psychopathology.

Psychopathology in children with epilepsy: a meta-analysis.

OBJECTIVE: To examine the types and severity of psychopathology in children with epilepsy. METHODS: A series of meta-analyses were conducted to review 46 studies, including 2,434 children with epilepsy. RESULTS: Effect sizes were medium to large for comparisons with children from the general population, which indicates that children with epilepsy are at increased risk for psychopathology, including internalizing and externalizing behavior problems. Comparisons with children with another chronic illness revealed small to medium effect sizes, indicating that psychopathology in children with epilepsy may partly be attributed to chronicity of the disease. Attention problems, thought problems, and social problems proved to be relatively specific to epilepsy. Comparisons with siblings suggested that psychopathology in children with epilepsy may be associated with family factors, especially where behavioral disorders appear to be more generic. CONCLUSIONS: Clinicians should consider both neurological and psychosocial factors, including the family system, when treating psychopathology in children with epilepsy.

Family factors and psychopathology in children with epilepsy: a literature review.

PURPOSE: From a social interactional and ecological framework, studies were reviewed that (1) compared family factors in children with epilepsy with those in children from normative groups, healthy children, children with a chronic illness, or siblings; and (2) examined the relationship between distinct family factors and child psychopathology. RESULTS: Compared with control groups, families with a child with epilepsy generally fare worse on the whole range of family factors, indicating lower parent-child relationship quality, more depression in mothers, and problems with family functioning. Significant associations were apparent between distinct family factors, especially parental psychological control, parental attributions about epilepsy, and family members' satisfaction with family relationships, and psychopathology in children with epilepsy. CONCLUSION: Future childhood epilepsy research might benefit from the examination of the simultaneous contribution of distinct family factors to child psychopathology, within a broad multifactorial framework that also includes neurological and medication factors.