Mother-Infant Interaction and Maternal Postnatal Psychological Distress Associate with Child's Social-Emotional Development During Early Childhood: A FinnBrain Birth Cohort Study.

We studied the effects of mother-infant interaction and maternal pre- and postnatal psychological distress on children's social-emotional problems and competences, as well as whether interaction quality moderates the association between distress and children's outcomes. Maternal pre- and postnatal psychological distress were measured using the SCL and EPDS questionnaires, whereas mother-infant interaction was measured when the child was 8 months old using the EA Scales. Children's social-emotional development was measured using the BITSEA questionnaire at 2 years old and using the SDQ questionnaire at 4 years old, where higher maternal structuring was associated with fewer social-emotional problems in children and higher maternal sensitivity was associated with greater social-emotional competence in children at 2 years old. Further, higher postnatal distress was found associated with greater social-emotional problems at 2 years old, though neither these effects nor moderating effects at 4 years old were observed after multiple-comparison corrections. Our findings support direct associations of both mother-infant interaction and maternal postnatal psychological distress with children's social-emotional development during toddlerhood.

Child social-emotional and behavioral problems and competencies contribute to changes in developmental functioning during Early Intervention.

This study examined how social-emotional and behavioral (SEB) problems and competencies contribute to changes in developmental functioning among children enrolled in Part C Early Intervention (EI), a U.S. program supporting young children with developmental delays and disabilities. The sample included 1,055 children enrolled in EI from 2011-2019 (mean age at EI entry = 17 months; 64% male; 72% marginalized racial and ethnic backgrounds). Standardized developmental assessments, drawn from administrative records, characterized developmental functioning at EI entry and exit and parents reported SEB functioning. Hierarchical regression analyses revealed that SEB problems and competencies interacted in predicting change in developmental functioning from EI entry to exit. Monitoring, identifying, and addressing SEB problems and competencies may optimize developmental outcomes for young children with developmental delays and disabilities.

Negative associations between maternal prenatal hair cortisol and child socioemotional problems.

Maternal prenatal distress can participate in the programming of offspring development, in which exposure to altered maternal long-term cortisol levels as measured by hair cortisol concentrations (HCC) may contribute. Yet, studies investigating whether and how maternal prenatal HCC associates with problems in child socioemotional development are scarce. Furthermore, questions remain regarding the timing and potential sex-specificity of fetal exposure to altered cortisol levels and whether there are interactions with maternal prenatal distress, such as depressive symptoms. The subjects were drawn from those FinnBrain Birth Cohort families that had maternal reports of child socioemotional problems (the Brief Infant-Toddler Social and Emotional Assessment [BITSEA] at 2 years and/or the Strengths and Difficulties Questionnaire [SDQ] at 5 years) as follows: HCC1 population: maternal mid-pregnancy HCC measured at gestational week 24 with 5 cm segments to depict cortisol levels from the previous five months (n = 321); and HCC2 population: end-of-pregnancy HCC measured 1-3 days after childbirth (5 cm segment; n = 121). Stepwise regression models were utilized in the main analyses and a sensitivity analysis was performed to detect potential biases. Negative associations were observed between maternal HCC2 and child BITSEA Total Problems at 2 years but not with SDQ Total difficulties at 5 years, and neither problem score was associated with HCC1. In descriptive analyses, HCC2 was negatively associated with Internalizing problems at 2 years and SDQ Emotional problems at 5 years. A negative association was observed among 5-year-old girls between maternal HCC1 and SDQ Total Difficulties and the subscales of Conduct and Hyperactivity/inattentive problems. When interactions were also considered, inverse associations between HCC2 and BITSEA Internalizing and Dysregulation Problems were observed in subjects with elevated prenatal depressive symptoms. It was somewhat surprising that only negative associations were observed between maternal HCC and child socioemotional problems. However, there are previous observations of elevated end-of-pregnancy cortisol levels associating with better developmental outcomes. The magnitudes of the observed associations were, as expected, mainly modest. Future studies with a focus on the individual changes of maternal cortisol levels throughout pregnancy as well as studies assessing both maternal and child HPA axis functioning together with child socioemotional development are indicated.

Trajectories of maternal depressive and anxiety symptoms and child's socio-emotional outcome during early childhood.

Maternal symptoms of depression and anxiety during pregnancy and early postnatal years are suggested to impose differential negative effects on child's socio-emotional development depending on the characteristics of the symptoms, such as timing, intensity, and persistence. The aim of this study was to identify trajectories of maternal depressive and anxiety symptoms from pregnancy until 2 years postpartum and to examine their relationship with child socio-emotional problems and competence at 2 and 5 years of age. The sample included 1208 mother-infant dyads from FinnBrain Birth Cohort study. Latent growth mixture modelling (LGMM) was utilized to model the trajectories of maternal depressive symptoms, measured using the Edinburgh Postnatal Depression Scale (EPDS), and general anxiety, measured with Symptom Checklist-90 (SCL-90) at 14, 24, and 34 weeks' gestation (gw) and at 3, 6 and 24 months postpartum. Maternal depression was also assessed at 12 months. Child socio-emotional problems and competence were evaluated using the Brief Infant Toddler Social Emotional Assessment (BITSEA) at 2 years and Strengths and Difficulties Questionnaire (SDQ) at 5 years. Relevant background factors and maternal concurrent symptomatology were controlled for. The trajectories of maternal depressive and anxiety symptoms were associated negatively with differential aspects of child long term socio-emotional outcomes from early toddlerhood to preschool years. The trajectories of depressive symptoms and high-level persistent symptoms that continued from pregnancy to two years of child age had the strongest negative association with child outcomes. This highlights the importance of identifying and treating maternal symptomatology, especially that of depression, as early as possible.

The influence of loss to follow-up in autism screening research: Taking stock and moving forward.

BACKGROUND: How best to improve the early detection of autism spectrum disorder (ASD) is the subject of significant controversy. Some argue that universal ASD screeners are highly accurate, whereas others argue that evidence for this claim is insufficient. Relatedly, there is no clear consensus as to the optimal role of screening for making referral decisions for evaluation and treatment. Published screening research can meaningfully inform these questions-but only through careful consideration of children who do not complete diagnostic follow-up. METHODS: We developed two simulation models that re-analyze the results of a large-scale validation study of the M-CHAT-R/F by Robins et al. (2014, Pediatrics, 133, 37). Model #1 re-analyzes screener accuracy across six scenarios, each reflecting different assumptions regarding loss to follow-up. Model #2 builds on this by closely examining differential attrition at each point of the multi-step detection process. RESULTS: Estimates of sensitivity ranged from 40% to 94% across scenarios, demonstrating that estimates of accuracy depend on assumptions regarding the diagnostic status of children who were lost to follow-up. Across a range of plausible assumptions, data also suggest that children with undiagnosed ASD may be more likely to complete follow-up than children without ASD, highlighting the role of clinicians and caregivers in the detection process. CONCLUSIONS: Using simulation modeling as a quantitative method to examine potential bias in screening studies, analyses suggest that ASD screening tools may be less accurate than is often reported. Models also demonstrate the critical importance of every step in a detection process-including steps that determine whether children should complete an additional evaluation. We conclude that parent and clinician decision-making regarding follow-up may contribute more to detection than is widely assumed.

Time-sensitive testing pressures and COVID-19 outcomes: are socioeconomic inequalities over the first year of the pandemic explained by selection bias?

BACKGROUND: There are many ways in which selection bias might impact COVID-19 research. Here we focus on selection for receiving a polymerase-chain-reaction (PCR) SARS-CoV-2 test and how known changes to selection pressures over time may bias research into COVID-19 infection. METHODS: Using UK Biobank (N = 420,231; 55% female; mean age = 66.8 [SD = 8·11]) we estimate the association between socio-economic position (SEP) and (i) being tested for SARS-CoV-2 infection versus not being tested (ii) testing positive for SARS-CoV-2 infection versus testing negative and (iii) testing negative for SARS-CoV-2 infection versus not being tested. We construct four distinct time-periods between March 2020 and March 2021, representing distinct periods of testing pressures and lockdown restrictions and specify both time-stratified and combined models for each outcome. We explore potential selection bias by examining associations with positive and negative control exposures. RESULTS: The association between more disadvantaged SEP and receiving a SARS-CoV-2 test attenuated over time. Compared to individuals with a degree, individuals whose highest educational qualification was a GCSE or equivalent had an OR of 1·27 (95% CI: 1·18 to 1·37) in March-May 2020 and 1·13 (95% CI: 1.·10 to 1·16) in January-March 2021. The magnitude of the association between educational attainment and testing positive for SARS-CoV-2 infection increased over the same period. For the equivalent comparison, the OR for testing positive increased from 1·25 (95% CI: 1·04 to 1·47), to 1·69 (95% CI: 1·55 to 1·83). We found little evidence of an association between control exposures, and any considered outcome. CONCLUSIONS: The association between SEP and SARS-CoV-2 testing changed over time, highlighting the potential of time-specific selection pressures to bias analyses of COVID-19. Positive and negative control analyses suggest that changes in the association between SEP and SARS-CoV-2 infection over time likely reflect true increases in socioeconomic inequalities.

Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers.

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10-5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate -0.006 kg/m2, 95% CI -0.009 to -0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.

Educational inequality in multimorbidity: causality and causal pathways. A mendelian randomisation study in UK Biobank.

BACKGROUND: Multimorbidity, typically defined as having two or more long-term health conditions, is associated with reduced wellbeing and life expectancy. Understanding the determinants of multimorbidity, including whether they are causal, may help with the design and prioritisation of prevention interventions. This study seeks to assess the causality of education, BMI, smoking and alcohol as determinants of multimorbidity, and the degree to which BMI, smoking and alcohol mediate differences in multimorbidity by level of education. METHODS: Participants were 181,214 females and 155,677 males, mean ages 56.7 and 57.1 years respectively, from UK Biobank. We used a Mendelian randomization design; an approach that uses genetic variants as instrumental variables to interrogate causality. RESULTS: The prevalence of multimorbidity was 55.1%. Mendelian randomization suggests that lower education, higher BMI and higher levels of smoking causally increase the risk of multimorbidity. For example, one standard deviation (equivalent to 5.1 years) increase in genetically-predicted years of education decreases the risk of multimorbidity by 9.0% (95% CI: 6.5 to 11.4%). A 5 kg/m2 increase in genetically-predicted BMI increases the risk of multimorbidity by 9.2% (95% CI: 8.1 to 10.3%) and a one SD higher lifetime smoking index increases the risk of multimorbidity by 6.8% (95% CI: 3.3 to 10.4%). Evidence for a causal effect of genetically-predicted alcohol consumption on multimorbidity was less strong; an increase of 5 units of alcohol per week increases the risk of multimorbidity by 1.3% (95% CI: 0.2 to 2.5%). The proportions of the association between education and multimorbidity explained by BMI and smoking are 20.4% and 17.6% respectively. Collectively, BMI and smoking account for 31.8% of the educational inequality in multimorbidity. CONCLUSIONS: Education, BMI, smoking and alcohol consumption are intervenable causal risk factors for multimorbidity. Furthermore, BMI and lifetime smoking make a considerable contribution to the generation of educational inequalities in multimorbidity. Public health interventions that improve population-wide levels of these risk factors are likely to reduce multimorbidity and inequalities in its occurrence.

Investigating effect modification between childhood maltreatment and genetic risk for cardiovascular disease in the UK Biobank.

Cardiovascular disease (CVD) is influenced by genetic and environmental factors. Childhood maltreatment is associated with CVD and may modify genetic susceptibility to cardiovascular risk factors. We used genetic and phenotypic data from 100,833 White British UK Biobank participants (57% female; mean age = 55.9 years). We regressed nine cardiovascular risk factors/diseases (alcohol consumption, body mass index [BMI], low-density lipoprotein cholesterol, lifetime smoking behaviour, systolic blood pressure, atrial fibrillation, coronary heart disease, type 2 diabetes, and stroke) on their respective polygenic scores (PGS) and self-reported exposure to childhood maltreatment. Effect modification was tested on the additive and multiplicative scales by including a product term (PGS*maltreatment) in regression models. On the additive scale, childhood maltreatment accentuated the effect of genetic susceptibility to higher BMI (Peffect modification: 0.003). Individuals not exposed to childhood maltreatment had an increase in BMI of 0.12 SD (95% CI: 0.11, 0.13) per SD increase in BMI PGS, compared to 0.17 SD (95% CI: 0.14, 0.19) in those exposed to all types of childhood maltreatment. On the multiplicative scale, similar results were obtained for BMI though these did not withstand to Bonferroni correction. There was little evidence of effect modification by childhood maltreatment in relation to other outcomes, or of sex-specific effect modification. Our study suggests the effects of genetic susceptibility to a higher BMI may be moderately accentuated in individuals exposed to childhood maltreatment. However, gene*environment interactions are likely not a major contributor to the excess CVD burden experienced by childhood maltreatment victims.

Glycoprotein acetyls and depression: Testing for directionality and potential causality using longitudinal data and Mendelian randomization analyses.

BACKGROUND: Inflammation is associated with depression, but causality remains unclear. We investigated potential causality and direction of effect between inflammation and depression. METHODS: Using data from the ALSPAC birth cohort (n = 4021; 42.18 % male), we used multivariable regression to investigate bidirectional longitudinal associations of GlycA and depression and depression symptoms, assessed at ages 18y and 24y. We used two-sample Mendelian randomization (MR) to investigate potential causality and directionality. Genetic variants for GlycA were obtained from UK Biobank (UKB) (N = 115,078); for depression from the Psychiatric Genomics Consortium and UKB (N = 500,199); and for depressive symptoms (N = 161,460) from the Social Science Genetic Association Consortium. In addition to the Inverse Variance Weighted method, we used sensitivity analyses to strengthen causal inference. We conducted multivariable MR adjusting for body mass index (BMI) due to known genetic correlation between inflammation, depression and BMI. RESULTS: In the cohort analysis, after adjusting for potential confounders we found no evidence of associations between GlycA and depression symptoms score or vice versa. We observed an association between GlycA and depression (OR = 1∙18, 95 % CI: 1∙03-1∙36). MR suggested no causal effect of GlycA on depression, but there was a causal effect of depression on GlycA (mean difference in GlycA = 0∙09; 95 % CI: 0∙03-0∙16), which was maintained in some, but not all, sensitivity analyses. LIMITATIONS: The GWAS sample overlap could incur bias. CONCLUSION: We found no consistent evidence for an effect of GlycA on depression. There was evidence that depression increases GlycA in the MR analysis, but this may be confounded/mediated by BMI.

Higher attention bias for fear at 8 months of age is associated with better socioemotional competencies during toddlerhood.

BACKGROUND: In previous studies, an attention bias for signals of fear and threat has been related to socioemotional problems, such as anxiety symptoms, and socioemotional competencies, such as altruistic behaviors in children, adolescents and adults. However, previous studies lack evidence about these relations among infants and toddlers. AIMS: Our aim was to study the association between the individual variance in attention bias for faces and, specifically, fearful faces during infancy and socioemotional problems and competencies during toddlerhood. STUDY DESIGN AND SUBJECTS: The study sample was comprised of 245 children (112 girls). We explored attentional face and fear biases at the age of 8 months using eye tracking and the face-distractor paradigm with neutral, happy and fearful faces and a scrambled-face control stimulus. Socioemotional problems and competencies were reported by parents with the Brief Infant and Toddler Social Emotional Assessment (BITSEA) when children were 24 months old. OUTCOME MEASURES AND RESULTS: A higher attentional fear bias at 8 months of age was related to higher levels of socioemotional competence at 24 months of age (ß = .18, p = .008), when infants' sex and temperamental affectivity, maternal age, education and depressive symptoms were controlled. We found no significant association between attentional face or fear bias and socioemotional problems. CONCLUSIONS: We found that the heightened attention bias for fearful faces was related to positive outcomes in early socioemotional development. Longitudinal study designs are needed to explore the changes in the relation between the attention bias for fear or threat and socioemotional development during early childhood.

Reciprocal Associations Between Language Ability and Social Functioning Development in Pre-verbal Autistic Children.

Longitudinal research on language abilities and social functioning in young children suggests that gains in one domain affect gains in the other. However, few studies have examined inter-relations of language and social functioning jointly among young children diagnosed with autism spectrum disorder (ASD). Pre-verbal toddlers with ASD are a group of particular clinical relevance, given that greater language abilities at school entry have been associated with positive long-term adjustment in many areas, including adaptive and social functioning. Reduced attention to and engagement in social interactions among autistic toddlers who are not yet speaking may interfere with language development concurrently and over time. The present study examined reciprocal associations between language ability and social functioning over a 2-year period across three time points in a sample of 90 pre-verbal autistic toddlers using cross-lagged panel analyses conducted in MPlus. Cross-lagged panel analyses revealed significant within-timepoint synchronous correlations, within-domain autoregressive paths over time, and as hypothesized, reciprocal significance in all cross-lagged paths. For very young pre-verbal children with ASD, language ability and social functioning appear to exert concurrent and cascading developmental influences on one another. Targeting both language and social functioning simultaneously may enhance intervention efficacy for very young pre-verbal children with ASD.

Screening Infants Through Adolescents for Social/Emotional/Behavioral Problems in a Pediatric Network.

OBJECTIVE: To assess changes in screening completion in a diverse, 7-clinic network after making annual screening for social/emotional/behavioral (SEB) problems the standard of care for all infant through late adolescent-aged patients and rolling out a fully automated screening system tied to the electronic medical record and patient portal. METHODS: In 2017, the Massachusetts General Hospital made SEB screening using the age-appropriate version of the Pediatric Symptom Checklist the standard of care in its pediatric clinics for all patients aged 2.0 months to 17.9 years. Billing records identified all well-child visits between January 1, 2016 and December 31, 2019. For each visit, claims were searched for billing for an SEB screen and the electronic data warehouse was queried for an electronically administered screen. A random sample of charts was reviewed for other evidence of screening. Chi-square analyses and generalized estimating equations assessed differences in screening over time and across demographic groups. RESULTS: Screening completion (billing and/or electronic) significantly increased from 2016 (37.2%) through 2019 (2017 [46.2%] vs 2018 [66.8%] vs 2019 [70.9%]; χ2 (3) =112652.33, P < .001), with an even higher prevalence found after chart reviews. Most clinics achieved screening levels above 90% by the end of 2019. Differences among demographic groups were small and dependent on whether data were aggregated at the clinic or system level. CONCLUSIONS: Following adoption of a best-practice policy and implementation of an electronic system, SEB screening increased in all age groups and clinics. Findings demonstrate that the AAP recommendation for routine psychosocial assessment is feasible and sustainable.

Exploring the impact of selection bias in observational studies of COVID-19: a simulation study.

BACKGROUND: Non-random selection of analytic subsamples could introduce selection bias in observational studies. We explored the potential presence and impact of selection in studies of SARS-CoV-2 infection and COVID-19 prognosis. METHODS: We tested the association of a broad range of characteristics with selection into COVID-19 analytic subsamples in the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK Biobank (UKB). We then conducted empirical analyses and simulations to explore the potential presence, direction and magnitude of bias due to this selection (relative to our defined UK-based adult target populations) when estimating the association of body mass index (BMI) with SARS-CoV-2 infection and death-with-COVID-19. RESULTS: In both cohorts, a broad range of characteristics was related to selection, sometimes in opposite directions (e.g. more-educated people were more likely to have data on SARS-CoV-2 infection in ALSPAC, but less likely in UKB). Higher BMI was associated with higher odds of SARS-CoV-2 infection and death-with-COVID-19. We found non-negligible bias in many simulated scenarios. CONCLUSIONS: Analyses using COVID-19 self-reported or national registry data may be biased due to selection. The magnitude and direction of this bias depend on the outcome definition, the true effect of the risk factor and the assumed selection mechanism; these are likely to differ between studies with different target populations. Bias due to sample selection is a key concern in COVID-19 research based on national registry data, especially as countries end free mass testing. The framework we have used can be applied by other researchers assessing the extent to which their results may be biased for their research question of interest.

Characterizing Accommodations by Parents of Young Children with Autism: A Mixed Methods Analysis.

Symptoms of autism influence families' participation in daily activities, but few studies have broadly explored the types of accommodations caregivers make to their family's routines after their child is diagnosed with autism. The current study used a mixed-methods approach to characterize the rate and types of accommodations made by 171 families and the child and family characteristics that predicted accommodations. Most families (91%) endorsed making accommodations in the past year. Lower income, older child age, marginalized racial/ethnic identity, and higher levels of child problem behavior predicted accommodations in a greater number of domains. Thematic analysis illuminated the types of accommodations caregivers made and their motivation for making these lifestyle adjustments. Findings have important implications for parent-mediated interventions and policy.

Prevalence and Co-Occurrence of Developmental and Emotional-Behavioral Problems in Young Children.

OBJECTIVE: A limited number of studies have estimated the prevalence of emotional-behavioral disorders among young children. None have assessed their co-occurrence with developmental delays using standardized assessment tools. Our objective was to estimate the prevalence of emotional-behavioral disorders and their co-occurrence with developmental delays among young children (2-5.5 years). METHODS: Parents of young children (N = 987) enrolled from pediatric waiting rooms completed developmental-behavioral screening questionnaires. Based on results, 585 families were invited to and 439 completed evaluations that included structured diagnostic interviews with parents to assess child psychopathology (Preschool Age Psychiatric Assessment (PAPA)), developmental testing with children (including the Bayley Scales of Infant and Toddler Development, third Edition for children ≤ 42 months; Differential Ability Scales, second Edition for older children), and videotaped observation to establish whether autism risk was sufficient to warrant further evaluation. RESULTS: According to PAPA algorithms, 23.0% of children met criteria for a DSM-IV disorder, while 9% qualified for a developmental delay. Presence of delay doubled the odds of having a DSM-IV disorder (OR = 2.1; CI: 1.02-4.3), and presence of disorder doubled the odds of having a moderate-to-severe developmental delay (OR=2.0; CI: 1.10-3.50). Prevalence of DSM-IV disorders (48.8% (95% CI: 33.5-64.5%)) and developmental delays (57.5% (95% CI: 41.7-71.9%)) were both higher among children at risk for autism. While developmental delay did not vary by race/ethnicity, prevalence of DSM-IV disorders was lower among African-American/Black (10.6%; CI: 2.9-18.3) and Hispanic/Latino children (11.1%; CI: 4.3-17.9). CONCLUSIONS: Developmental delays and emotional-behavioral disorders among young children seen in pediatric settings are characterized by high prevalence and substantial co-occurrence.

Bilingual and Monolingual Autistic Toddlers: Language and Social Communication Skills.

Parents of children diagnosed with autism spectrum disorders (ASD) express concern about raising their children bilingually, and often hear advice from professionals against the use of bilingualism. The current study examined the relation between bilingualism and the language and social communication skills of toddlers diagnosed with ASD (N = 353) in the US, while controlling for socioeconomic risk factors. Structural equation modeling showed no differences in language skills between bilingual Spanish-English speaking children and monolingual English-speaking (p = .596) or monolingual Spanish-speaking (p = .963) children and showed a bilingual advantage on socialization skills when comparing bilingual and monolingual English-speaking children (p = .001). Parents of autistic children exposed to Spanish and English should be encouraged to raise their child bilingually if it best suits familial needs.