Gene - maltreatment interplay in adult ADHD symptoms: main role of a gene-environment correlation effect in a Brazilian population longitudinal study.

Childhood maltreatment correlates with attention-deficit/hyperactivity disorder (ADHD) in previous research. The interaction between ADHD genetic predisposition and maltreatment's impact on ADHD symptom risk remains unclear. We aimed to elucidate this relationship by examining the interplay between a polygenic score for ADHD (ADHD-PGS) and childhood maltreatment in predicting ADHD symptoms during young adulthood. Using data from the 2004 Pelotas (Brazil) birth cohort comprising 4231 participants, we analyzed gene-environment interaction (GxE) and correlation (rGE). We further explored rGE mechanisms through mediation models. ADHD symptoms were assessed at age 18 via self-report (Adult Self Report Scale - ASRS) and mother-reports (Strength and Difficulties Questionnaire - SDQ). The ADHD-PGS was derived from published ADHD GWAS meta-analysis. Physical and psychological child maltreatment was gauged using the Parent-Child Conflict Tactics Scale (CTSPC) at ages 6 and 11, with a mean score utilized as a variable. The ADHD-PGS exhibited associations with ADHD symptoms on both ASRS (ß = 0.53; 95% CI: 0.03; 1.03, p = 0.036), and SDQ (ß = 0.20; 95% CI: 0.08; 0.32, p = 0.001) scales. The total mean maltreatment score was associated with ADHD symptoms using both scales [(ßASRS = 0.51; 95% CI: 0.26;0.77) and (ßSDQ = 0.24; 95% CI: 0.18;0.29)]. The ADHD-PGS was associated with total mean maltreatment scores (ß = 0.09; 95% CI: 0.01; 0.17; p = 0.030). Approximately 47% of the total effect of ADHD-PGS on maltreatment was mediated by ADHD symptoms at age 6. No evidence supported gene-environment interaction in predicting ADHD symptoms. Our findings underscore the significant roles of genetics and childhood maltreatment as predictors for ADHD symptoms in adulthood, while also indicating a potential evocative mechanism through gene-environment correlation.

Genetic risk for attention-deficit/hyperactivity disorder predicts cognitive decline and development of Alzheimer's disease pathophysiology in cognitively unimpaired older adults.

Attention-deficit/hyperactivity disorder (ADHD) persists in older age and is postulated as a risk factor for cognitive impairment and Alzheimer's Disease (AD). However, these findings rely primarily on electronic health records and can present biased estimates of disease prevalence. An obstacle to investigating age-related cognitive decline in ADHD is the absence of large-scale studies following patients with ADHD into older age. Alternatively, this study aimed to determine whether genetic liability for ADHD, as measured by a well-validated ADHD polygenic risk score (ADHD-PRS), is associated with cognitive decline and the development of AD pathophysiology in cognitively unimpaired (CU) older adults. We calculated a weighted ADHD-PRS in 212 CU individuals without a clinical diagnosis of ADHD (55-90 years). These individuals had baseline amyloid-ß (Aß) positron emission tomography, longitudinal cerebrospinal fluid (CSF) phosphorylated tau at threonine 181 (p-tau181), magnetic resonance imaging, and cognitive assessments for up to 6 years. Linear mixed-effects models were used to test the association of ADHD-PRS with cognition and AD biomarkers. Higher ADHD-PRS was associated with greater cognitive decline over 6 years. The combined effect between high ADHD-PRS and brain Aß deposition on cognitive deterioration was more significant than each individually. Additionally, higher ADHD-PRS was associated with increased CSF p-tau181 levels and frontoparietal atrophy in CU Aß-positive individuals. Our results suggest that genetic liability for ADHD is associated with cognitive deterioration and the development of AD pathophysiology. Findings were mostly observed in Aß-positive individuals, suggesting that the genetic liability for ADHD increases susceptibility to the harmful effects of Aß pathology.

Trajectory of maternal depression and parasomnias.

Maternal depressive symptoms are associated with poorer sleep quality in their children. Although parasomnias can occur at any age, this group of sleep disorders is more common in children. The aim of this study was to assess whether maternal depression trajectories predict parasomnias at the age of 11 years. Data were from a Birth Cohort of 4231 individuals followed in the city of Pelotas, Brazil. Maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS) at 12, 24, and 48 months, and 6 and 11 years postpartum. Maternal depression trajectories were calculated using a group-based modelling approach. Information on any parasomnias (confused arousals, sleepwalking, night terrors, and nightmares) was provided by the mother. Five trajectories of maternal depressive symptoms were identified: chronic-low (34.9%), chronic-moderate (41.4%), increasing (10.3%), decreasing (8.9%), and chronic-high (4.4%). The prevalence of any parasomnia at the age of 11 years was 16.8% (95% confidence interval [CI] 15.6%-18.1%). Confusional arousal was the most prevalent type of parasomnia (14.5%) and varied from 8.7% to 14.7%, 22.9%, 20.3%, and 27.5% among children of mothers at chronic-low, moderate-low, increasing, decreasing, and chronic-high trajectories, respectively (p < 0.001). Compared to children from mothers in the chronic-low trajectory, the adjusted prevalence ratio for any parasomnia was 1.58 (95% CI 1.29-1.94), 2.34 (95% CI 1.83-2.98), 2.15 (95% CI 1.65-2.81), and 3.07 (95% CI 2.31-4.07) among those from mothers in the moderate-low, increasing, decreasing, and chronic-high trajectory groups, respectively (p < 0.001). In conclusion, parasomnias were more prevalent among children of mothers with chronic symptoms of depression.

Early risk factors for conduct problem trajectories from childhood to adolescence: the 2004 Pelotas (BRAZIL) Birth Cohort.

Conduct problems are associated with an increased risk of a wide range of physical, mental, and social problems. However, there is still uncertainty about how early risk factors differentiate different developmental patterns of conduct problems and whether findings replicate across diverse social contexts. We aimed to identify developmental trajectories of conduct problems, and test early risk factors, in the 2004 Pelotas Birth Cohort in Brazil. Conduct problems were measured at ages 4, 6, 11, and 15 years from caregiver reports on the Child Behaviour Checklist (CBCL) and Strengths and Difficulties Questionnaire (SDQ). Conduct problem trajectories were estimated using group-based semi-parametric modeling (n = 3938). Multinomial logistic regression was used to examine associations between early risk factors and conduct problem trajectories. We identified four trajectories: three with elevated conduct problems, including early-onset persistent (n = 150; 3.8%), adolescence-onset (n = 286; 17.3%), and childhood-limited (n = 697; 17.7%), and one with low conduct problems (n = 2805; 71.2%). The three elevated conduct problem trajectories were associated with a wide range of sociodemographic risk factors, prenatal smoking, maternal mental health, harsh parenting, childhood trauma, and child neurodevelopmental risk factors. Early-onset persistent conduct problems were particularly associated with trauma, living without a father figure, and attention difficulties. The four trajectories of conduct problems from ages 4 to 15 years in this Brazilian cohort have similar longitudinal patterns to those identified in high-income countries. The results confirm previous longitudinal research and developmental taxonomic theories on the etiology of conduct problems in a Brazilian sample.

Effects of Two Early Parenting Programmes on Child Aggression and Risk for Violence in Brazil: a Randomised Controlled Trial.

Violence is a major public health problem globally, with the highest rates in low- and middle-income countries (LMICs) in the Americas and southern Africa. Parenting programmes in high-income countries can diminish risk for violence, by reducing risk factors such as child aggression and harsh parenting, and increasing protective factors such as child cognitive development and school readiness. However, there is critical need to identify low-cost programmes with replicable benefits that work in real-world LMICs contexts. A three-arm, randomised, single-blind trial evaluated effects of two low-cost, group-based parenting programmes recommended for LMICs (ACT: Raising Safe Kids; DBS: dialogic book-sharing) on child aggression (primary outcome), child development, parenting, maltreatment, and stress. Participants were 369 children with medium-high levels of aggression (mean age 3.1 years at baseline) in poor households. Interventions were implemented in city health and education services in southern Brazil. Maternal reports, filmed observations, child tasks, and hair cortisol were assessed at baseline, 1-month post-intervention, and 8-month follow-up. Intention-to-treat analyses compared each of ACT and DBS with a control group. Three hundred sixty-eight (99.7%) participants completed follow-up assessments 8 months after the interventions. There was no effect of ACT (standardised mean difference, SMD 0.11, 95% CI - 0.05, 0.27) or DBS (SMD 0.05, 95% CI - 0.11, 0.21) on the primary outcome of child aggression. ACT reduced harsh parenting behaviour post-intervention (SMD - 0.23; 95% CI - 0.46, - 0.01), but not at follow-up. DBS improved book-sharing practices at both time points (e.g., maternal sensitivity at follow-up SMD 0.33; 95% CI 0.08, 0.57). There were no benefits of either programme for other parenting, child development, or stress outcomes. Two parenting programmes in Brazil had small effects on parenting practices but did not reduce child aggression or several other important risk/protective factors for violence. Effective early interventions that reduce violence in real-world LMIC settings are highly desirable but may be challenging to achieve.

Women's multi-partner behavior, multi-partner fertility, and pregnancy outcomes: findings from the 2004 Pelotas Birth Cohort.

STUDY QUESTION: Do women with multi-partner fertility or multi-partner behavior conceive more often than women with a single partner? SUMMARY ANSWER: Women with multi-partner behavior conceived more frequently and had more children than non-multi-partner women and multi-partner fertility women. WHAT IS KNOWN ALREADY: Some women experience having biological children with more than one partner: those women are considered as multi-partner fertility. Women with multi-partner fertility have more children and are substantially less likely to have planned their first birth. Individuals with multi-partner fertility become parents at a younger age, largely with unintended first births, and often do so outside of marriage, compared to parents with two or more children from only one partner. Unmarried women, particularly, are at greater risk of having unintended births. Studies are still scarce and there is a need to assess the contribution of women's multi-partners fertility and multi-partner behavior to family composition, particularly in low- and middle-income countries. STUDY DESIGN, SIZE, DURATION: This longitudinal birth cohort study evaluated 1215 mothers whose children belonging to the 2004 Pelotas Birth Cohort were their first pregnancy, and who attended the perinatal, 48-month, 6-year, and 11-year follow-ups. Information was obtained from responses to a questionnaire. The number of years at risk of having children was treated as the exposure, and woman's multi-partner behavior and multi-partner fertility, dichotomized as 'Yes' or 'No', were considered endogenous treatment variables. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from mothers with a first pregnancy, and with information available from the perinatal, 48-month, 6-year, and 11-year follow-ups, were evaluated. The exposures studied were women's multi-partner behavior and multi-partner fertility (i.e. conceiving/giving birth), and the outcomes evaluated were the number of pregnancies, the number of children currently alive, and experience of unintended pregnancies from the birth of the child belonging to the 2004 birth cohort until 11 years later. Crude and adjusted risk ratios (RRs) were estimated through Poisson regression with endogenous treatment effects, robust standard errors, and their respective 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: Multi-partner behavior women had 16% (RR 1.16; 95% CI: 1.08-1.25) and 11% (RR 1.11; 95% CI 1.03-1.19) greater risk of having a new pregnancy and having more children alive, respectively, than those with non-multi-partner behavior. Women with multi-partner fertility had a 23% (RR 1.23; 95% CI: 1.11-1.37) and 20% (RR 1.20; 95% CI: 1.08-1.33) higher risk of having a new pregnancy and having more children alive, respectively, than single-partner fertility mothers. Women who had multiple partners (i.e. behavior), as well as those with multi-partner fertility, showed a lesser proportion of unintended pregnancies when compared to the non-multi-partner ones (34.08%; 95% CI: 28.12-40.60 vs 36.17%; 95% CI: 31.93-40.63), compared to their counterparts' single partners fertility (33.16%; 95% CI: 26.83-40.17 vs 36.26%; 95% CI: 31.85-40.92), although these findings were not statistically significant. LIMITATIONS, REASONS FOR CAUTION: The mothers who were not included in the study owing to missing data for some of the follow-up had 5-11 years of education, a low socio-economic level, and were younger, thus the number of pregnancies may be underestimated because these groups presented a high number of pregnancies and children alive. We did not have information about the complete woman's conjugal history. Therefore, misclassification error of the exposure may be present and, consequently, the measures of association may be underestimated. Furthermore, this study was not truly representative of the Pelotas study female population. WIDER IMPLICATIONS OF THE FINDINGS: In this study of multi-partner behavior and fertility, women who have multiple partners may be less likely to get married and have a stable partner. Compared to single-partner women, multi-partner fertility and multi-partner behavior women may predominantly become pregnant for the purpose of having children, rather than accidentally. STUDY FUNDING/COMPETING INTEREST(S): This article is based on data from the study 'Pelotas Birth Cohort, 2004' conducted by the Postgraduate Program in Epidemiology at the Universidade Federal de Pelotas, with the collaboration of the Brazilian Public Health Association (ABRASCO). From 2009 to 2013, the Wellcome Trust supported the 2004 birth cohort study. The World Health Organization, National Support Program for Centers of Excellence (PRONEX), Brazilian National Research Council (CNPq), Brazilian Ministry of Health, and Children's Pastorate supported previous phases of the study, and also was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)-Finance Code 001. The authors declare that the supported agencies have no role in any step of performing this study. No conflicts of interest exist. TRIAL REGISTRATION NUMBER: N/A.

BDNF Levels According to Variations in the CACNA1C Gene: Sex-Based Disparity.

The CACNA1C gene encodes the pore-forming alpha-1c subunit of L-type voltage-gated calcium channels. The calcium influx through these channels regulates the transcription of the brain-derived neurotrophic factor (BDNF). Polymorphisms in this gene have been consistently associated with psychiatric disorders, and alterations in BDNF levels are a possible biological mechanism to explain such associations. Here, we sought to investigate the effect of the CACNA1C rs1006737 and rs4765913 polymorphisms and their haplotypes on serum BDNF concentration. We further aim to investigate the regulatory function of these SNPs and the ones linked to them. The study enrolled 641 young adults (362 women and 279 men) in a cross-sectional population-based survey. Linear regression was used to test the effects of polymorphisms and haplotypes on BDNF levels adjusted for potential confounders. Moreover, regulatory putative functional roles were assessed using in silico approach. BDNF levels were not associated with CACNA1C polymorphisms/haplotype in the total sample. When the sample was stratified by sex, checking the effect of polymorphisms on men and women separately, the A-allele of rs4765913 was associated with lower BDNF levels in women compared with the TT genotype (p = 0.010). The AA (rs1006737-rs4765913) haplotype was associated with BDNF levels in opposite directions regarding sex, with lower levels of BDNF in women (p = 0.040) compared to those without this haplotype, while with higher levels in men (p = 0.027). These findings were supported by the presence of regulatory marks only on the male fetal brain. Our results suggest that the BDNF levels regulation may be a potential mechanism underpinning the association between CACNA1C and psychiatric disorders, with a differential role in women and men.

Temperament traits mediate the relationship between CACNA1C polymorphisms and bipolar disorder in cisgender women.

The influence of temperament traits on bipolar disorder (BD) has been investigated. Both temperament traits and BD are partially genetically determined and seem to be influenced by variations in the CACNA1C gene. These variations presented a significant interactive effect with biological sex, although studies that evaluate this relationship are scarce. Here, we assessed the mediation effect of temperament traits on the relationship between two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) and BD according to sex. This is a cross-sectional study consisting of 878 Caucasian individuals (508 women and 370 men), aged 18-35, enrolled in a population-based study in the city of Pelotas, Southern Brazil. BD diagnosis was evaluated using the clinical interview MINI 5.0, and temperament traits were assessed via the application of the Affective and Emotional Composite Temperament Scale (AFECTS). Mediation models were tested using the modeling tool PROCESS (version 3.3) for SPSS. Bootstrapping-enhanced mediation analyses in women indicated that traits anger (39%) and caution (27%) mediated the association between the rs4765913 SNP and BD, while traits volition (29%), anger (35%), and caution (29%) mediated the association between the AA haplotype (rs1006737-rs4765913) and the BD. No effect was encountered for cisgender men. Our model revealed that paths from CACNA1C SNPs to BD are mediated by specific temperament traits in women, reinforcing the definition of temperament traits as endophenotypes.

Impact of covid-19 pandemic over depressive symptoms among mothers from a population-based birth cohort in southern brazil.

PURPOSE: Our aim was to assess the impact of COVID-19 on depressive symptoms among mothers from a population-based birth cohort in Pelotas, Southern Brazil. METHODS: A subgroup of mothers from the Pelotas 2004 Birth Cohort was assessed pre-pandemic (November,2019 to March,2020) and mid-pandemic (August-December,2021). In both follow-ups, depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Pre-pandemic (T1) and pandemic-related predictors (T2) were analyzed. Prevalence of depression (EPDS score ≥ 13) at T1 and T2 were compared with chi-square test. Changes in EPDS from T1 to T2 were estimated by multivariate latent change score modelling. RESULTS: 1,550 women were assessed. Prevalence of depression increased 38.1% (from 18.9% at T1 to 26.1% at T2) (p < 0.001). At T1, higher schooling, higher family income and being employed or working were related to lower EPDS, whereas being beneficiary of a cash transfer program and a larger number of people living in the household predicted higher EPDS. The deterioration of ones' own perception of quality of overall health (ß = 0.191; SE = 0.028; p < 0.001) and worst family financial situation due to the pandemic (ß = 0.083; SE = 0.024; p = 0.001) predicted the increase in EPDS from T1 to T2. CONCLUSION: Almost two years after the beginning of the pandemic, the prevalence of depressive symptoms among the women was higher than before the pandemic. The deterioration of ones' own perception of quality of overall health and worst family financial situation due to the pandemic are proxies for the effect of COVID-19 pandemic (the true exposure of interest) in the women mental health.

Maternal depression trajectories in childhood, subsequent maltreatment, and adolescent emotion regulation and self-esteem: the 2004 Pelotas birth cohort.

This study aimed to examine the impact of maternal depressive symptoms trajectories on 15-year-old adolescents' self-esteem and emotion regulation and test the mediating role of child maltreatment in this association. The 2004 Pelotas Birth Cohort is an ongoing cohort study originally comprised of 4231 live births in a southern Brazilian city. We examined a subsample of 1949 adolescents at age 15 years. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale. Trajectories of maternal depression from 3 months until the 11-year follow-up were calculated using a group-based modeling approach. Child maltreatment at age 11 years was measured using the parent-report version of the Parent-Child Conflict Tactics Scale. Adolescent outcomes at age 15 years were assessed by the self-report version of the Rosenberg Self-esteem Scale and the Emotion Regulation Index for Children and Adolescents. Path model analysis was conducted using a structural equation modeling framework in Mplus software. All maternal depression trajectories were negatively associated with offspring self-esteem and emotion regulation compared to the reference group (low depression trajectory). There was a significant indirect effect of maternal depression trajectories on emotion regulation mediated via child maltreatment. No evidence of moderation by sex was found for any pathway. The effects of maternal depression on adolescents' emotion regulation are partly mediated by child maltreatment at age 11.

Association between preterm infant size at 1 year and ADHD later in life: data from 1993 and 2004 Pelotas Birth Cohorts.

The objective of this study is to examine the association between preterm infants' size at 1 year and attention-deficit/hyperactivity disorder (ADHD) assessed categorically and dimensionally in childhood and adolescence. We studied infants born < 37 weeks' gestation from two Brazilian birth cohorts (n = 653). ADHD was evaluated using the Development and Well-Being Assessment (DAWBA) interview at the age of 6 years in one cohort and by a structured interview according to DSM-5 criteria at 18 years in the other one. The presence of child attention difficulties was measured by the Strengths and Difficulties Questionnaire (SDQ) at 6 and 11 years in the 2004 and 1993 cohorts, respectively. We estimated associations of weight, length, head circumference, and BMI z-scores at 1-year chronological age with ADHD using Poisson Regression Model; and with attention difficulties using Linear Regression, adjusting for covariates. Mean birth weight was 2500 g and gestational age was 34.5 weeks. The aggregated ADHD prevalence in the two cohorts was 2.7%, and the median score for attention difficulties was 3.0. We found that increased head circumference at 1 year was associated with a lower risk of ADHD diagnosis (RR = 0.7, 95% CI 0.4, 0.9; p = 0.04 per standard deviation difference) and with fewer dimensional attention symptoms. In sensitivity analysis with other mental disorders, head circumference was associated with depression, but not with anxiety. Our findings emphasize poor head growth in the first year of life as a potential determinant of attentional difficulties in the preterm infant population.

ADHD in childhood predicts BMI and body composition measurements over time in a population-based birth cohort.

BACKGROUND/OBJECTIVES: Obesity has been reported as an attention-deficit hyperactivity disorder (ADHD) comorbidity. So far, few studies have aimed to explore the potential causal relationship between ADHD and obesity, as well as used other measures of body composition like fat-free mass (FFM) and fat mass (FM) as measures of obesity. This study aimed to test the association between ADHD and body composition (body mass index [BMI] and others) and to evaluate the potential causal relationship with obesity. SUBJECTS/METHODS: Data from the 1993 Pelotas (Brazil) birth cohort at age 11-, 15-, 18-, and 22-year follow-up was used. We performed a cross-lagged panel model (CLPM) analysis between ADHD symptoms and BMI to explore the causal relationship between both traits. Finally, we tested whether ADHD, inattention, and hyperactivity symptom scales were associated with BMI, FM, and FFM at 22 years. RESULTS: In the CLPM, higher ADHD scores at age 11 predicted higher BMI at age 15 (ß = 0.055, 95% CI [0.037; 0.073]). ADHD symptoms at age 11 was also associated with a decrease in the FFM (ß = -0.16, 95% CI [-0.28; -0.05]), and an increase in the BMI (ß = 0.17, 95% CI [0.10; 0.23]) and FM (ß = 0.17, 95% CI [0.06; 0.29]) at 22 years. At 22 years of age, ADHD was associated with FFM and FM. Moreover, an increase in BMI was observed with an increase in several symptoms of ADHD in general (ß = 0.06, 95% CI [0.004; 0.12]), and hyperactivity symptoms (ß = 0.15, 95% CI [0.05; 0.25]). CONCLUSION: ADHD at 11 years predicted a higher BMI at 15 years, and body fat composition in adulthood, suggesting higher scores on ADHD symptoms in early life may be a critical point for body composition in early adulthood. The hyperactivity symptoms may play an important role in the BMI increase.

Construction and validation of the Oxford Neurodevelopment Assessment (OX-NDA) in 1-year-old Brazilian children.

BACKGROUND: Over 250 million children under 5 years, globally, are at risk of developmental delay. Interventions during the first 2 years of life have enduring positive effects if children at risk are identified, using standardized assessments, within this window. However, identifying developmental delay during infancy is challenging and there are limited infant development assessments suitable for use in low- and middle-income (LMIC) settings. Here, we describe a new tool, the Oxford Neurodevelopment Assessment (OX-NDA), measuring cognition, language, motor, and behaviour, outcomes in 1-year-old children. We present the results of its evaluation against the Bayley Scales of Infant Development IIIrd edition (BSID-III) and its psychometric properties. METHODS: Sixteen international tools measuring infant development were analysed to inform the OX-NDA's construction. Its agreement with the BSID-III, for cognitive, motor and language domains, was evaluated using intra-class correlations (ICCs, for absolute agreement), Bland-Altman analyses (for bias and limits of agreement), and sensitivity and specificity analyses (for accuracy) in 104 Brazilian children, aged 12 months (SD 8.4 days), recruited from the 2015 Pelotas Birth Cohort Study. Behaviour was not evaluated, as the BSID-III's adaptive behaviour scale was not included in the cohort's protocol. Cohen's kappas and Cronbach's alphas were calculated to determine the OX-NDA's reliability and internal consistency respectively. RESULTS: Agreement was moderate for cognition and motor outcomes (ICCs 0.63 and 0.68, p < 0.001) and low for language outcomes (ICC 0.30, p < 0.04). Bland-Altman analysis showed little to no bias between measures across domains. The OX-NDA's sensitivity and specificity for predicting moderate-to-severe delay on the BSID-III was 76, 73 and 43% and 75, 80 and 33% for cognition, motor and language outcomes, respectively. Inter-rater (k = 0.80-0.96) and test-rest (k = 0.85-0.94) reliability was high for all domains. Administration time was < 20 minutes. CONCLUSION: The OX-NDA shows moderate agreement with the BSID-III for identifying infants at risk of cognitive and motor delay; agreement was low for language delay. It is a rapid, low-cost assessment constructed specifically for use in LMIC populations. Further work is needed to evaluate its use (i) across domains in populations beyond Brazil and (ii) to identify language delays in Brazilian children.

Attention-deficit/hyperactivity disorder has a state-dependent association with asthma: The role of systemic inflammation in a population-based birth cohort followed from childhood to adulthood.

There is a high comorbidity between attention-deficit/hyperactivity disorder (ADHD) and asthma, and inflammation has been proposed as a potential pathophysiological mechanism behind this association. Most studies conducted so far have used a cross-sectional design, and none has evaluated the prevalence of asthma symptoms in patients with ADHD followed from childhood to adulthood. We relied on data from the 1993 Pelotas birth cohort to evaluate the association between ADHD and asthma in patients with distinct patterns of incidence, persistence and remission, and to explore the potential role of inflammatory markers in the comorbidity. We analyzed data from 3281 individuals from the 1993 Pelotas birth cohort collected at birth (1993), 11 years (2004), 18 years (2011), and 22 years (2015). Subjects were first classified according to their ADHD and asthma status as early-onset (EO) persistent (positive screening for ADHD at 11 years and diagnosis of ADHD according to DSM-5, except criterion E, at either 18 or 22 years), EO-remittent (positive screening for ADHD at 11 years only), late-onset (diagnosis of ADHD according to DSM-5, except criterion E, at 18 or 22 years only), or healthy subjects (negative for both conditions in all evaluation). After controlling for confounders, significant associations were observed between EO-remittent ADHD and EO-remittent asthma (OR 1.68, 95% CI 1.11-2.55), EO-persistent ADHD and EO-persistent asthma (OR 4.33, 95% CI 1.65-11.34), and between late-onset ADHD and late-onset asthma (OR 1.86, 95% CI 1.28-2.70), suggesting a state-dependent association. Serum interleukin-6 (IL-6) and C-reactive protein (CRP) were measured at the 18- and 22-year evaluations and compared between subjects positive for ADHD, asthma, and subjects with both or none conditions, regardless of the previously defined trajectories. Subjects with comorbid ADHD and asthma presented higher levels of IL-6 at the 18- and 22-year evaluations when compared to subjects negative for both conditions. Our results demonstrate a state-dependent association between ADHD and asthma despite underlying trajectories. Higher levels of serum IL-6 in patients with both conditions suggest that a pro-inflammatory environment might have a role in the pathophysiological mechanisms underlying the comorbidity.

Maternal perinatal depression and infant sleep problems at 1 year of age: Subjective and actigraphy data from a population-based birth cohort study.

This study used data from 2,222 mothers and infants participating in a population-based birth cohort to verify whether maternal depression in the perinatal period was associated with poor infant sleep. Mothers who scored ≥13 points on the Edinburgh Postnatal Depression Scale at 16-24 weeks of gestation and/or 3 months after delivery were considered perinatally depressed. The main outcome variable was poor infant sleep at 12 months of age, defined as >3 night wakings, nocturnal wakefulness >1 hr or total sleep duration <9 hr. Infant sleep data were obtained with the Brief Infant Sleep Questionnaire (BISQ) and 24-hr actigraphy monitoring. Prevalence of perinatal depression in the sample was 22.3% (95% confidence interval [CI], 20.5-24.0). After Poisson regression, infants of depressed mothers showed an adjusted relative risk (RR) of 1.44 (95% CI, 1.00-2.08; p = .04) for >3 night wakings with questionnaire-derived data. When actigraphy data were analysed, no association was found between perinatal depression and poor infant sleep (adjusted RR, 1.20; 95% CI, 0.82-1.74; p = .35). In conclusion, although mothers in the depressed group were more likely to report more night wakings, objective data from actigraphy did not replicate this finding. Dysfunctional cognition, maternal behavioural factors and sleep impairment associated with perinatal depression may affect the mother's impression of her infant's sleep.

Single nucleotide polymorphisms of taste genes and caries: a systematic review and meta-analysis.

OBJECTIVE: The aim of the present study was to systematically review the literature investigating the single nucleotide polymorphisms (SNP) related to taste genes and their influence on caries. MATERIAL AND METHODS: Search was performed in five databases to respond to the question: 'Are the polymorphisms of taste genes associated with dental caries?'. Studies in humans were included. Assessment of quality of studies, meta-analysis and sensitivity analysis were performed. RESULTS: Seven studies were included in the systematic review and two in meta-analysis. Most of studies (71.4%) presented cohort design with low-level of evidence. A total of 4,032 individuals were evaluated. Four different taste genes (TAS1R2, TAS2R38, TAS1R3 and GLUT2) and 12 SNPs were reported. Most SNPs of taste genes showed a protective effect of the minor allele against dental caries. Meta-analysis included the SNP rs713598 placed in the TAS2R38 gene. The results suggest an effect of the heterozygote genotype (CG), which was associate with low caries experience (OR = 0.35 CI95% [0.17-0.75]). However, the genotype GG was not associated (OR = 0.17 CI95% [0.03-1.04]). Sensitivity analysis showed an important influence of one study in the results. CONCLUSIONS: SNP of taste genes seems to be associated with caries experience. Causal inferences should be interpreted with caution and the results must be replicated in different populations.

Low neurodevelopmental performance and behavioural/emotional problems at 24 and 48 months in Brazilian children exposed to acetaminophen during foetal development.

BACKGROUND: Several studies have reported that there is an association between developmental and emotional/behavioural problems in children exposed to acetaminophen during foetal development. However, few studies have focused on development and behavioural outcomes in early life. OBJECTIVES: To test the association between prenatal exposure to acetaminophen and low neurodevelopmental performance at 24 months and behavioural/emotional problems at 48 months of life. METHODS: We used data from the 2004 Pelotas Birth Cohort, a population-based longitudinal prospective study. Neurodevelopment was evaluated at 24 months using Battelle's Developmental Inventory (BDI) (n = 3737). We assessed global function as well as each domain (personal-social, adaptative, motor, cognitive, and communication). Behavioural/emotional problems were assessed at 48 months using the Child Behaviour Checklist (CBCL) (n = 3624). We used the CBCL total, externalising, and internalising symptomatology and individual subscales (withdrawn, somatic complaints, anxious/depressed, social problems, cognitive problems, attention problems, aggressive behaviour, and rule-breaking behaviour). Acetaminophen use during pregnancy was retrospectively assessed at the perinatal follow-up. Poisson regression and multiple linear regression analyses were used to test the association, adjusting for several family and maternal sociodemographic and health factors, medication use during pregnancy, and the sex of the child. RESULTS: Acetaminophen exposure during prenatal development was not associated with low neurodevelopmental performance at 24 months assessed using the BDI or to emotional and behavioural problems assessed at 48 months using the CBCL in the adjusted models. CONCLUSIONS: We cannot confirm the existence of an association between acetaminophen used during pregnancy and low neurodevelopmental performance at 24 months and emotional/behavioural problems at 48 months of life based on the present results.

Associations of acetaminophen use during pregnancy and the first year of life with neurodevelopment in early childhood.

BACKGROUND: Over-the-counter analgesic use during pregnancy, particularly acetaminophen, may be associated with negative developmental outcomes in children. OBJECTIVE: Estimate associations of prenatal and early-life exposure to acetaminophen in early childhood with cognitive, motor, and language skills in two birth cohorts. METHODS: The American Project Viva cohort (1217 mother-child pairs enrolled 1999-2002) assessed cognition at approximately 3 years using the Peabody Picture Vocabulary Test and the Wide Range Achievement of Visual Motor Abilities (WRAVMA). The Brazilian 2015 Pelotas Birth Cohort (3818 mother-child pairs) assessed cognition at 2 years using the INTERGROWTH-21st Neurodevelopment Assessment. We used linear regression to estimate associations of acetaminophen use during pregnancy (Project Viva and Pelotas) and infancy (Project Viva) with children's cognitive scores adjusted for maternal age, pre-pregnancy body mass index, education, parity, race/ethnicity, smoking and alcohol use during pregnancy, depression during pregnancy, antibiotic and ibuprofen use during pregnancy, household income, and child's sex. RESULTS: In Project Viva, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was associated with lower WRAVMA drawing scores (ß -1.51, 95% CI -2.92, -0.10). However, in Pelotas, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was not associated with INTER-NDA motor scores (ß 0.02; 95% CI -0.05, 0.09) and was associated with higher INTER-NDA total scores (ß 0.08, 95% CI 0.01, 0.16). Other comparisons did not show evidence for any associations. CONCLUSIONS: Inconsistencies and lack of specificity of the findings did not clarify the research question considering that we still have a large variability and uncertainty to define the risk or safety in the use of acetaminophen related to cognition in early childhood. More studies using better exposure assessment and better confounding variables are needed to clarify these associations.

Effects of parenting interventions on child and caregiver cortisol levels: systematic review and meta-analysis.

BACKGROUND: Nurturing care, in which children are raised in engaging and safe environments, may reduce child stress and shape hypothalamic-pituitary-adrenal axis functioning. Hence, parent-training programs may impact child cortisol levels, as well as behavioral, social and health outcomes. We conducted a systematic review of the impact of parent-training interventions on children's and caregivers' cortisol levels, and meta-analyzed the results. METHODS: In January 2020, searches in PubMed, LILACS, ERIC, Web of Science, Scielo, Scopus, PsycNET and POPLINE databases were conducted, and two independent researchers screened the results for eligible studies - randomized trials that assessed the impact of parent-training interventions on child or caregiver cortisol levels. Random effects were used to pool the estimates, separately for children and caregivers, and for children's morning and evening cortisol levels, as well as change across the day. RESULTS: A total of 27 eligible studies were found. Data from 19 studies were extracted and included in the meta-analyses, with 18 estimates of child cortisol levels and 5 estimates for caregiver cortisol levels. The pooled effect size (standardized mean difference) for the effects of parent training programs on morning child cortisol was 0.01 (95%CI: - 0.14 to 0.16; I2: 47.5%), and for caregivers it was 0.04 (95%CI: - 0.22 to 0.30; I2: 0.0%). Similar null results were observed for child evening cortisol and for the slope between morning and evening child cortisol. No evidence of publication bias was found. CONCLUSION: Existing evidence shows no effect of parent-training interventions on child or caregiver post-intervention cortisol. Researchers are encouraged to adopt standardized protocols to improve evaluation standards, to test for intervention effects on psychosocial outcomes that are theorized to mediate the effects on biomarkers, and to use additional biomarkers for chronic stress.

Genes and SNPs in the pathway of immune response and caries risk: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to pool the data on Single Nucleotide Polymorphisms (SNPs) in immune response genes associated with dental caries. Nineteen studies were included in the review and 18 in the meta-analysis. Twenty-two SNPs were evaluated, which are linked to six different genes (MBL2, LFT, MASP2, DEFB1, FCN2 and MUC5B). Most SNPs (81.8%) are related to the possible functional impact on protein coding. The MBL2 gene was associated with caries experience in the analysis of the homozygote (OR = 2.12 CI95%[1.12-3.99]) and heterozygote (OR = 2.22 CI95%[1.44-3.44]) genotypes. The MUC5B gene was associated according to an analysis of the heterozygous genotype (OR = 1.83 CI95%[1.08-3.09]). Thus, SNPs related to immune response genes are linked to the phenotype of caries experience. Although the meta-analysis showed that the genes MBL2 and MUC5B were associated with caries, these results should be interpreted with caution due to the quality of the evidence.