Application of the Instrumental Inequalities to a Mendelian Randomization Study With Multiple Proposed Instruments

BACKGROUND: Investigators often support the validity of Mendelian randomization (MR) studies, an instrumental variable approach proposing genetic variants as instruments, via. subject matter knowledge. However, the instrumental variable model implies certain inequalities, offering an empirical method of falsifying (but not verifying) the underlying assumptions. Although these inequalities are said to detect only extreme assumptio

Poverty from fetal life onward and child brain morphology

Poverty is a risk factor for impaired child development, an association possibly mediated by brain morphology. Previous studies lacked prospective poverty assessments during pregnancy and did not stratify by majority/minority status. We investigated the association of household poverty from fetal life forward with brain morphological differences at age 10 years, in 2166 mother–child dyads. Overall, the results showed no associations between any poverty exposure early in life and brain volumes. However, there was the evidence of timing effects: children exposed to poverty in utero had smaller amygdala volumes (B =  − 0.18, 95%CI − 0.30; − 0.07, p(FDR-adjusted) = 0.009). There were also differences in associations by majority/minority status (cerebral white matter: p for interaction = 0.04). Dutch children exposed to childhood poverty showed smaller cerebral white matter volumes than their control (B =  − 0.26, 95%CI − 0.45; − 0.06, p(FDR-adjusted) = 0.035). This association was not observed in the minority population (B =  − 0.05, 95%CI − 0.23; 0.12, p(FDR-adjusted) = 0.542). The smaller cerebral white matter volume mediated the association between childhood poverty and poorer school performance in Dutch children. Our findings point to the importance of poverty exposure in the fetal period and suggest different mechanisms and vulnerabilities across majority/minority groups

Are all threats equal? Associations of childhood exposure to physical attack versus threatened violence with preadolescent brain structure

Background: Neurodevelopmental studies of childhood adversity often define threatening experiences as those involving harm or the threat of harm. Whether effects differ between experiences involving harm (“physical attack”) versus the threat of harm alone (“threatened violence”) remains underexplored. We hypothesized that while both types of experiences would be associated with smaller preadolescent global and corticolimbic brain volumes, associations with physical attack would be greater. Methods: Generation R Study researchers (the Netherlands) acquired T1-weighted scans from 2905 preadolescent children, computed brain volumes using FreeSurfer, and asked mothers whether their children ever experienced physical attack (n = 202) or threatened violence (n = 335). Using standardized global (cortical, subcortical, white matter) and corticolimbic (amygdala, hippocampus, anterior cingulate cortex, orbitofrontal cortex) volumes, we fit confounder-adjusted models. Results: Physical attack was associated with smaller global volumes (βcortical=−0.14; 95% CI: −0.26, −0.02); βwhite matter= −0.16; 95% CI: − 0.28, − 0.03) and possibly some corticolimbic volumes, e.g., βamygdala/ICV-adjusted= −0.10 (95% CI: −0.21, 0.01). We found no evidence of associations between threatened violence and smaller volumes in any outcome; instead, such estimates were small, highly uncertain, and positive in direction. Conclusions: Experiences of physical attack and threatened violence may have quantitively different neurodevelopmental effects. Thus, differences between types of threatening experiences may be neurodevelopmentally salient.</p

Behavioral and neurostructural correlates of childhood physical violence victimization:Interaction with family functioning

Violence victimization may cause child behavior problems and neurostructural differences associated with them. Healthy family environments may buffer these effects, but neural pathways explaining these associations remain inadequately understood. We used data from 3154 children (x̅age  = 10.1) to test whether healthy family functioning moderated possible associations between violence victimization, behavior problems, and amygdala volume (a threat-responsive brain region). Researchers collected data on childhood violence victimization, family functioning (McMaster Family Assessment Device, range 0-3, higher scores indicate healthier functioning), and behavior problems (Achenbach Child Behavior Checklist [CBCL] total problem score, range 0-117), and they scanned children with magnetic resonance imaging. We standardized amygdala volumes and fit confounder-adjusted models with "victimization × family functioning" interaction terms. Family functioning moderated associations between victimization, behavior problems, and amygdala volume. Among lower functioning families (functioning score = 1.0), victimization was associated with a 26.1 (95% confidence interval [CI]: 9.9, 42.4) unit higher CBCL behavior problem score, yet victimized children from higher functioning families (score = 3.0) exhibited no such association. Unexpectedly, victimization was associated with higher standardized amygdala volume among lower functioning families (ŷ = 0.5; 95% CI: 0.1, 1.0) but lower volume among higher functioning families (ŷ = -0.4; 95% CI: -0.7, -0.2). Thus, healthy family environments may mitigate some neurobehavioral effects of childhood victimization.</p

Parenting, young children\u27s behavioral self‐regulation and the quality of their peer relationships

The quality of young children\u27s peer relationships is important for their development, and it is assumed that parenting and self-regulation skills shape children\u27s behavior when interacting with peers. In this multi-informant-multi-method study, we examined the direct and mediated associations between preschool parenting, children\u27s behavioral self-regulation, and peer aggression and peer relationship problems in elementary school-aged children and extended previous work by examining both positive and negative parenting of both mothers and fathers. In a large community sample (n = 698) of parents and children who were between 1 and 6 years old, we obtained information on observed maternal sensitivity, mother- and father-reported harsh discipline, observed child self-regulation, and child-reported aggression towards peers, peer rejection and victimization. Results from a structural equation model showed that maternal sensitivity was prospectively associated with children\u27s behavioral self-regulation and that lower levels of behavioral self-regulation were associated with higher levels of children\u27s peer aggression and peer relationship problems. However, children\u27s behavioral self-regulation did not mediate the association between maternal sensitivity and peer relationship problems. In addition, higher levels of paternal, but not maternal, harsh discipline were directly associated with more peer relationship problems, but again no mediation was found. The results highlight the importance of maternal sensitivity for children\u27s behavioral self-regulation and the role of paternal harsh discipline for the quality of children\u27s later peer relationships. Our findings suggest it is important to take maternal and paternal parenting practices into account as they might have different effects on the child

Television viewing through ages 2-5 years and bullying involvement in early elementary school

BACKGROUND: High television exposure time at young age has been described as a potential risk factor for developing behavioral problems. However, less is known about the effects of preschool television on subsequent bullying involvement. We examined the association between television viewing time through ages 2-5 and bullying involvement in the first grades of elementary school. We hypothesized that high television exposure increases the risk of bullying involvement. METHOD: TV viewing time was assessed repeatedly in early childhood using parental report. To combine these repeated assessments we used latent class analysis. Four exposure classes were identified and labeled “low”, “mid-low”, “mid-high” and “high”. Bullying involvement was assessed by teacher questionnaire (n = 3423, mean age 6.8 years). Additionally, peer/self-report of bullying involvement was obtained using a peer nomination procedure (n = 1176, mean age 7.6 years). We examined child risk of being a bully, victim or a bully-victim (compared to being uninvolved in bullying). RESULTS: High television exposure class was associated with elevated risks of bullying and victimization. Also, in both teacher- and child-reported data, children in the high television exposure class were more likely to be a bully-victim (OR = 2.11, 95% CI: 1.42-3.13 and OR = 3.68, 95% CI: 1.75-7.74 respectively). However, all univariate effect estimates attenuated and were no longer statistically significant once adjusted for maternal and child covariates. CONCLUSIONS: The association between television viewing time through ages 2-5 and bullying involvement in early elementary school is confounded by maternal and child socio-demographic characteristics

Prenatal and postnatal psychological symptoms of parents and family functioning: the impact on child emotional and behavioural problems

Although relations of various parental psychological problems and family functioning with child development are well documented, it remains unclear whether specific prenatal or specific postnatal risk factors are independently associated with child emotional and behavioural problems, or whether observed associations can be explained by general parental psychopathology. Using a stepwise approach, we examined the effects of prenatal and postnatal parental depressive symptoms, prenatal and postnatal hostility of the parents, as well as prenatal family functioning on the risk of child emotional and behavioural problems. This study was embedded in Generation R: a population-based cohort from foetal life onwards. Mothers and fathers of 2,698 children provided information about depressive symptoms, symptoms of hostility and family functioning during pregnancy and 3 years after birth. Mother and father each reported on child behaviour when the child was 3 years old. Parental depressive symptoms increased the risk of child emotional and behavioural problems, but this increase was explained by postnatal parental hostile behaviour. Postnatal symptoms of hostility of mothers (OR = 1.34, p value <0.001) and postnatal symptoms of hostility of fathers (OR = 1.30, p value <0.001) each contributed independently to the risk of child emotional and behavioural problems. Postnatal parental hostility is associated with an increased risk of child emotional and behavioural problems, independent of parental depressive symptoms. These findings suggest that prevention and intervention strategies should focus on psychological symptoms of both mothers and fathers, in particular on hostile behaviour, in families with young children

Bidirectional Associations between Fussy Eating and Functional Constipation in Preschool Children

ObjectiveTo examine bidirectional associations between a child's fussy eating behavior and functional constipation.Study designParticipants were 4823 children enrolled in a prospective cohort study from pregnancy onward. We assessed fussy eating at age 4 years with the Child Eating Behavior Questionnaire, and assessed functional constipation using ROME II and III criteria with parental questionnaires at age 2, 3, 4, and 6 years.ResultsHigher food fussiness at age 4 years was associated with a greater risk of functional constipation at both 4 years (OR, 1.30; 95% CI, 1.20-1.42; P < .001 per 1 SD increase) and 6 years (OR, 1.12; 95% CI, 1.03-1.23; P < .05 per 1 SD increase). The converse was also observed; previous constipation predicted a greater risk of being a fussy eater at age 4 years (constipation at 2 years: OR, 2.05; 95% CI 1.43-2.94; P < .001; constipation at 3 years: OR, 1.72; 95% CI, 1.26-2.35, P < .001). Path analyses confirmed that the association between fussy eating and functional constipation was indeed bidirectional, showing that functional constipation at age 3 years predicted fussy eater classification at age 4 years (β = 0.06; P < .001), which in turn predicted functional constipation at age 6 years (β = 0.08: P < .001) independent of each other.ConclusionA vicious cycle might develop in which children with functional constipation develop unhealthy eating behavior, which in turn increases the risk of functional gastrointestinal disease

Long-term association of pregnancy and maternal brain structure:the Rotterdam Study

The peripartum period is the highest risk interval for the onset or exacerbation of psychiatric illness in women’s lives. Notably, pregnancy and childbirth have been associated with short-term structural and functional changes in the maternal human brain. Yet the long-term effects of pregnancy on maternal brain structure remain unknown. We investigated a large population-based cohort to examine the association between parity and brain structure. In total, 2,835 women (mean age 65.2 years; all free from dementia, stroke, and cortical brain infarcts) from the Rotterdam Study underwent magnetic resonance imaging (1.5 T) between 2005 and 2015. Associations of parity with global and lobar brain tissue volumes, white matter microstructure, and markers of vascular brain disease were examined using regression models. We found that parity was associated with a larger global gray matter volume (β = 0.14, 95% CI = 0.09–0.19), a finding that persisted following adjustment for sociodemographic factors. A non-significant dose-dependent relationship was observed between a higher number of childbirths and larger gray matter volume. The gray matter volume association with parity was globally proportional across lobes. No associations were found regarding white matter volume or integrity, nor with markers of cerebral small vessel disease. The current findings suggest that pregnancy and childbirth are associated with robust long-term changes in brain structure involving a larger global gray matter volume that persists for decades. Future studies are warranted to further investigate the mechanism and physiological relevance of these differences in brain morphology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-021-00818-5