To sleep or to breastfeed: Associations between feeding method and sleep in infants and children.

AIM: This study aimed to understand the association between feeding method, specifically breastfeeding versus non-breastfeeding, at 6 and 12 months and infant sleep over the first 3 years of life. METHODS: A sample of 444 mother-infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment cohort were analysed. Based on retrospective maternal reports between 3-24 months, infants' breastfeeding status was determined at 6 and 12 months. Nocturnal sleep duration, longest period of consecutive sleep, and total sleep over 24 h were measured by maternal reports at 6, 12, 24 and 36 months. RESULTS: Generalized Estimating Equations revealed no significant association between feeding status, both at 6 and 12 months, and nocturnal sleep duration or total sleep over 24 h between 6-36 months (p > 0.05). However, breastfeeding at both 6 and 12 months was associated with shorter periods of consecutive sleep, at 6 and 12 months (p < 0.05) but not at 24 and 36 months (p > 0.05). CONCLUSION: Our findings suggest that breastfeeding seems to be associated with more infant sleep fragmentation but not with total sleep duration in early infancy. However, this sleep fragmentation does not persist into later infancy and early toddlerhood.

Maternal prenatal depression is associated with dysregulation over the first five years of life moderated by child polygenic risk for comorbid psychiatric problems.

Dysregulation is a combination of emotion, behavior, and attention problems associated with lifelong psychiatric comorbidity. There is evidence for the stability of dysregulation from childhood to adulthood, which would be more fully characterized by determining the likely stability from infancy to childhood. Early origins of dysregulation can further be validated and contextualized in association with environmental and biological factors, such as prenatal stress and polygenic risk scores (PRS) for overlapping child psychiatric problems. We aimed to determine trajectories of dysregulation from 3 months to 5 years (N = 582) in association with maternal prenatal depression moderated by multiple child PRS (N = 232 pairs with available PRS data) in a prenatal cohort. Mothers reported depression symptoms at 24-26 weeks' gestation and child dysregulation at 3, 6, 18, 36, 48, and 60 months. The PRS were for major depressive disorder, attention deficit hyperactivity disorder, cross disorder, and childhood psychiatric problems. Covariates were biological sex, maternal education, and postnatal depression. Analyses included latent classes and regression. Two dysregulation trajectories emerged: persistently low dysregulation (94%), and increasingly high dysregulation (6%). Stable dysregulation emerged at 18 months. High dysregulation was associated with maternal prenatal depression, moderated by PRS for child comorbid psychiatric problems. Males were at greater risk of high dysregulation.

Negative emotionality as a candidate mediating mechanism linking prenatal maternal mood problems and offspring internalizing behaviour.

Negative emotionality (NE) was evaluated as a candidate mechanism linking prenatal maternal affective symptoms and offspring internalizing problems during the preschool/early school age period. The participants were 335 mother-infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment project. A Confirmatory Bifactor Analysis (CFA) based on self-report measures of prenatal depression and pregnancy-specific anxiety generated a general factor representing overlapping symptoms of prenatal maternal psychopathology and four distinct symptom factors representing pregnancy-specific anxiety, negative affect, anhedonia and somatization. NE was rated by the mother at 18 and 36 months. CFA based on measures of father, mother, child-rated measures and a semistructured interview generated a general internalizing factor representing overlapping symptoms of child internalizing psychopathology accounting for the unique contribution of each informant. Path analyses revealed significant relationships among the general maternal affective psychopathology, the pregnancy- specific anxiety, and the child internalizing factors. Child NE mediated only the relationship between pregnancy-specific anxiety and the child internalizing factors. We highlighted the conditions in which prenatal maternal affective symptoms predicts child internalizing problems emerging early in development, including consideration of different mechanistic pathways for different maternal prenatal symptom presentations and child temperament.

Sleep terrors in early childhood and associated emotional-behavioral problems.

STUDY OBJECTIVES: While sleep terrors are associated with emotional-behavioral problems in school-aged children and adults, little is known about these associations in early childhood, when sleep terrors prevalence is at its highest. Moreover, studies using a longitudinal design and controlling for confounding variables are scarce. This study's objective was to determine whether the frequency of sleep terrors in toddlers predicts emotional-behavioral problems during the preschool years. METHODS: Participants (n = 324) were enrolled in the prospective Maternal Adversity Vulnerability and Neurodevelopment cohort study. The frequency of sleep terrors in children was assessed at 12, 18, 24, and 36 months using maternal reports. Children's emotional-behavioral problems were measured at 48 and 60 months using the Child Behavior Checklist. Relevant confounders linked to the child, mother, and environment were also taken into consideration. RESULTS: The frequency of sleep terrors was relatively stable across early childhood (16.7-20.5%). A generalized estimating equation revealed that the frequency of sleep terrors in early childhood was associated with increased emotional-behavioral problems at 4 and 5 years of age, more specifically with internalizing problems (P < .001), after controlling for child's sex, time point, family socioeconomic status, maternal depressive symptoms, and nighttime sleep duration. The frequency of sleep terrors was further associated with the emotionally reactive, anxious/depressed, and somatic complaints scales (P < .01). CONCLUSIONS: This longitudinal study provides further support for a high prevalence of sleep terrors in early childhood. Our findings show meaningful associations between higher frequency of sleep terrors and emotional-behavioral problems as early as toddlerhood, especially internalizing problems. CITATION: Laganière C, Gaudreau H, Pokhvisneva I, et al. Sleep terrors in early childhood and associated emotional-behavioral problems. J Clin Sleep Med. 2022;18(9):2253-2260.

Bacteriocins as a new generation of antimicrobials: toxicity aspects and regulations.

In recent decades, bacteriocins have received substantial attention as antimicrobial compounds. Although bacteriocins have been predominantly exploited as food preservatives, they are now receiving increased attention as potential clinical antimicrobials and as possible immune-modulating agents. Infections caused by antibiotic-resistant bacteria have been declared as a global threat to public health. Bacteriocins represent a potential solution to this worldwide threat due to their broad- or narrow-spectrum activity against antibiotic-resistant bacteria. Notably, despite their role in food safety as natural alternatives to chemical preservatives, nisin remains the only bacteriocin legally approved by regulatory agencies as a food preservative. Moreover, insufficient data on the safety and toxicity of bacteriocins represent a barrier against the more widespread use of bacteriocins by the food and medical industry. Here, we focus on the most recent trends relating to the application of bacteriocins, their toxicity and impacts.

Maternal antenatal depression and child mental health: Moderation by genomic risk for attention-deficit/hyperactivity disorder.

Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 × 10-4, R2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 × 10-9, R2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health.

Maternal symptoms of depression and sensitivity mediate the relation between maternal history of early adversity and her child temperament: The inheritance of circumstance.

We examined maternal depression and maternal sensitivity as mediators of the association between maternal childhood adversity and her child's temperament in 239 mother-child dyads from a longitudinal, birth cohort study. We used an integrated measure of maternal childhood adversity that included the Childhood Trauma Questionnaire and the Parental Bonding Index. Maternal depression was assessed with the Edinburgh Postnatal Depression Scale at 6 months postpartum. Maternal sensitivity was assessed with the Ainsworth maternal sensitivity scales at 6 months. A measure of "negative emotionality/behavioral dysregulation" was derived from the Early Childhood Behaviour Questionnaire administered at 36 months. Bootstrapping-based mediation analyses revealed that maternal depression mediated the effect of maternal childhood adversity on offspring negative emotionality/behavioral dysregulation (95% confidence interval [0.026, 0.144]). We also found a serial, indirect effect of maternal childhood adversity on child negative emotionality/behavioral mediated first by maternal depression and then by maternal sensitivity (95% confidence interval [0.031, 0.156]). Results suggest the intergenerational transmission of the effects of maternal childhood adversity to the offspring occurs through a two-step, serial pathway, involving maternal depression and maternal sensitivity.

Once and Again : History of Rearing Experiences and Psychosocial Parenting Resources at Six Months in Primiparous Mothers.

Animal and human studies suggest that parenting style is transmitted from one generation to the next. The hypotheses of this study were that (1) a mother's rearing experiences (G1) would predict her own parenting resources (G2) and (2) current maternal mood, motivation to care for her offspring, and relationship with her parents would underlie this association. In a subsample of 201 first-time mothers participating in the longitudinal Maternal Adversity, Vulnerability and Neurodevelopment project, we assessed a mother's own childhood maltreatment and rearing experiences (G1) using the Childhood Trauma Questionnaire and the Parental Bonding Instrument. At 6 months postpartum, mothers completed questionnaires on parenting stress (G2), symptoms of depression, maternal motivation, and current relationship with their own parents. The sample consisted of mostly high socioeconomic status mothers recruited from Montréal (n = 135) or Hamilton (n = 66), Canada, with an age range from 18 to 43 years (M = 29.41, SD = 4.85 years). More severe maltreatment and less supportive rearing by the mother's parents (G1) predicted increased parenting stress at 6 months (G2). These associations were mediated through distinct psychosocial pathways: maltreatment (G1) on parenting stress (G2) through symptoms of depression (Z = 2.297; p = .022); maternal rearing (G1) on parenting stress (G2) through maternal motivation (Z = -2.155; p = .031) and symptoms of depression (Z = -1.842; p = .065); and paternal rearing (G1) on parenting stress (G2) through current relationship with the father (Z = -2.617; p = .009). Maternal rearing experiences predict a mother's own parenting resources though distinct psychosocial pathways, including depressed mood, maternal motivation, and social support.

Dissecting maternal care: Patterns of maternal parenting in a prospective cohort study.

Parental care has a strong impact on neurodevelopment and mental health in the offspring. Although numerous animal studies have revealed that the parental brain is a highly complex system involving many brain structures and neuroendocrine systems, human maternal parenting as a multidimensional construct with cognitive, emotional, and behavioural components has not been characterised comprehensively. This unique multi-method analysis aimed to examine patterns of self-reported and observed parenting from 6 to 60 months postpartum in a cohort of 496 mothers (mean maternal age = 32 years). Self-report questionnaires assessed motivational components of mothering, parenting stress, parenting-related mood, maternal investment, maternal parenting style, mother-child relationship satisfaction, and mother-child bonding at multiple time points. Observed parenting variables included the Ainsworth Sensitivity Scales at 6 and 18 months, the Behavioral Evaluation Strategies Taxonomies at 6 months, an Etch-A-Sketch cooperation task at 48 months, and the Parent-Child Early Relationship Assessment at 60 months. To examine whether different latent constructs underlie these measures of maternal parenting, we conducted an exploratory factor analysis. Self-report measures of parenting correlated only weakly with behavioural observations. Factor analysis on a subsample (n = 197) revealed four latent factors that each explained from 7% to 11% of the variance in the data (32% total variance explained). Based on the loadings of the instruments, the factors were interpreted as: Supportive Parenting, Self-Enjoyment Parenting, Overwhelmed Parenting, and Affectionate Parenting. These factor scores showed specific associations with maternal education and depressive symptoms, as well as with child outcomes, including maternally reported internalising and externalising behavioural problems, school readiness, and child-reported symptoms of mental health. These findings parallel the complexity of the parental brain, suggesting that maternal parenting consists of multiple components, each of which is associated with different maternal characteristics and child outcomes.

Association Between Repeated Episodes of Gastroenteritis and Mental Health Problems in Childhood and Adolescence.

OBJECTIVE: The Avon Longitudinal Study of Parents and Children (ALSPAC) and Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) cohorts were used to determine whether repeated exposure to gastroenteritis in early life could predict risk for psychiatric problems in childhood and in ALSPAC adolescents. We determined whether inflammatory biomarkers moderated the association between repeated gastroenteritis and mental health in adolescents from ALSPAC. METHOD: Episodes of gastroenteritis from birth to 30 and 36 months were reported by mothers. Psychological problems were assessed using the total difficulties and subscale scores on the Revised Rutter Parent Scale for Preschool Children at 42 months and the Strengths and Difficulties Questionnaire (SDQ) at 81 months in ALSPAC. Presence of psychiatric disorders at 15.5 years was assessed using the Development and Well-Being Assessment (DAWBA) in ALSPAC. In the MAVAN replication cohort, total difficulties were assessed on the SDQ at 60 and 72 months. Serum interleukin-6 (IL-6) and C-reactive protein (CRP) at 9.5 years and CRP at 15.5 years were measured in ALSPAC participants. RESULTS: Repeated gastroenteritis associated with the total difficulties score in ALSPAC and MAVAN children. The ß values were small, indicating that the clinical relevance of these findings requires further investigation. Repeated gastroenteritis was significantly associated with an increased prevalence of externalizing disorders at age 15.5 years, but odds ratios were small. CRP or IL-6 at 9.5 years or CRP at 15.5 years did not significantly moderate the association between repeated gastroenteritis and prevalence of psychiatric disorders. CONCLUSION: Identifying factors associated with vulnerability to psychopathology is key to early identification of individuals at risk.

Maternal characteristics and behavioural/emotional problems in preschoolers: how they relate to sleep rhythmic movements at sleep onset.

Sleep rhythmic movements have been speculated to be a form of self-soothing. While this sleep-related movement has been associated with lower socioeconomic status, psychopathologies and maternal characteristics, prospective studies with sizeable sample and objective measurements are lacking. The objectives were: (a) to identify maternal characteristics predicting sleep rhythmic movements in children; and (b) to document behavioural/emotional problems in preschoolers with sleep rhythmic movements. Participants were mother-child dyads (N = 529) from the Adversity: Maternal Adversity, Vulnerability and Neurodevelopment cohort. Questionnaires evaluating socioeconomic status (prenatal), maternal depressive symptoms (prenatal, 48 months), sleep rhythmic movements (12, 18, 24, 36, 48 months), maternal anxiety trait (24 months) and children's behavioural/emotional problems (48 months) were used. Maternal sensitivity (accuracy and appropriateness of mother's responses to her baby's needs) was assessed objectively with a filmed mother-infant interaction (6 months). Generalized estimating equation was used to investigate associations between sleep rhythmic movements and maternal characteristics (depression, anxiety and sensitivity). Linear regressions were used to assess associations between sleep rhythmic movements and behavioural/emotional problems in children. Lower maternal sensitivity, higher maternal depressive symptoms and lower socioeconomic status predicted sleep rhythmic movements in children (p < 0.05). To our knowledge, this is the first study showing that sleep rhythmic movements are associated with lower maternal sensitivity, measured objectively. This study also builds on previous reports, by documenting an association between sleep rhythmic movements and behavioural/emotional problems even in preschoolers. The presence of psychosocial factors in sleep rhythmic movements aetiology should be considered in treatment.

Gestational age at birth and sleep duration in early childhood in three population-based cohorts.

BACKGROUND: Both preterm and post-term births have been associated with neonatal morbidity and mortality, including adverse impact on neurodevelopment. Important neural maturational processes take place during sleep in newborns, but findings on gestational duration and sleep in early childhood are contradictory and often derive from small clinical samples. We studied the association of gestational age at birth with sleep duration in early childhood in three population-based cohorts. METHODS: Gestational age at birth and sleep duration were assessed in three population-based cohort studies in The Netherlands (n = 6471), Singapore (n = 862), and Canada (n = 583). Gestational age at birth was assessed using ultrasound in pregnancy in combination with date of birth, and caregivers repeatedly reported on child sleep duration at three, six, 24, and 36 months of age. Generalized estimating equations were used, which were adjusted for confounders, and findings were pooled in a meta-analysis. RESULTS: Children born preterm (<37 weeks of gestation) showed longer sleep duration than children born at term; and children born post-term (≥42 weeks of gestation) showed shorter sleep duration. The meta-analysis indicated a small negative effect of gestational age on child sleep duration (effect size -0.11), when assessed in children born at term only. CONCLUSION: In early childhood, children with a lower gestational age have a longer sleep duration, even when they are born at term (37-42 weeks of gestation). These subtle yet consistent findings point to the importance of maturational processes during sleep, not only in premature children but also in children born at term after shorter gestational duration.

Maternal perceptions of paternal investment are associated with relationship satisfaction and breastfeeding duration in humans.

This study examined potential pathways in the associations between breastfeeding and mothers' relationship satisfaction, including her satisfaction with father involvement (FI) and parity, among mothers not working outside the home at 6 months. Mothers (n = 222) completed questionnaires at 4 time-points, 3 to 24 months postpartum as part of a longitudinal cohort study. In this study, we were interested in two main outcome variables: mothers' relationship satisfaction with their partner (RS) and continuation of breastfeeding after 3 months. Our first analysis revealed that breastfeeding at 3 months postpartum predicted decreased RS at 6 months postpartum, which was mediated by mothers' dissatisfaction with FI in infant caretaking at 6 months postpartum. These associations depended on mothers' parity: Multiparous breastfeeding mothers were the most dissatisfied with FI. Second, mothers' satisfaction with FI at 6 months also predicted increased RS at 24 months through increased RS at 12 months, but not through FI at 18 months. Third, we found that high dissatisfaction with FI at 6 months was the only significant predictor for the discontinuation of breastfeeding from 3 to 6 months postpartum. Our results suggest that multiparous breastfeeding mothers might be more dissatisfied with FI in caregiving than nonbreastfeeding mothers and primiparous breastfeeding mothers. Furthermore, mothers' satisfaction with FI seems a potent predictor of overall RS up to 24 months postpartum and the continuation of breastfeeding from 3 to 6 months postpartum, regardless of parity. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Uninterrupted Infant Sleep, Development, and Maternal Mood.

OBJECTIVES: Contrary to the importance of total sleep duration, the association between sleeping through the night and development in early infancy remains unclear. Our aims were to investigate the proportion of infants who sleep through the night (6- or 8-hour sleep blocks) at ages 6 and 12 months in a longitudinal cohort and to explore associations between sleeping through the night, mental and psychomotor development, maternal mood, and breastfeeding. METHODS: At 6 and 12 months of age, maternal reports were used to assess the longest period of uninterrupted infant sleep and feeding method (n = 388). Two different criteria were used to determine if infants slept through the night: 6 and 8 hours of uninterrupted sleep. Mental and psychomotor developmental indices (Bayley Scales of Infant Development II) and maternal mood (Center for Epidemiologic Studies Depression Scale) were measured at 6, 12, and 36 months of age. RESULTS: Using a definition of either 6 or 8 hours of uninterrupted sleep, we found that 27.9% to 57.0% of 6- and 12-month-old infants did not sleep through the night. Linear regressions revealed no significant associations between sleeping through the night and concurrent or later mental development, psychomotor development, or maternal mood (P > .05). However, sleeping through the night was associated with a much lower rate of breastfeeding (P < .0001). CONCLUSIONS: Considering that high proportions of infants did not sleep through the night and that no associations were found between uninterrupted sleep, mental or psychomotor development, and maternal mood, expectations for early sleep consolidation could be moderated.

Birth weight and catch up growth are associated with childhood impulsivity in two independent cohorts.

Individuals born after intrauterine growth restriction (IUGR) are more impulsive towards palatable foods, but it is not clear 1) if IUGR-related impulsivity is specific for foods and solely based on response inhibition and 2) if the development of impulsivity is due to being born IUGR per se or to growing up fast in the first few years of life (catch up growth). Children were classified in the IUGR group if the birth weight ratio was below 0.85. Delta z score for BMI was used as a measure of catch up growth. In MAVAN (N = 274), impulsivity was measured by the Information Sampling Task from the Cambridge Neuropsychological Test Automated Battery (IST - CANTAB), and in GUSTO using the Sticker Delay Task (N = 327). There is a significant effect of interaction between being born IUGR and the magnitude of catch up growth on the reflection impulsivity from IST-CANTAB at 60 months, in which greater catch up growth associates with greater impulsivity in the IST fixed condition in IUGR children. The finding was reproduced in children from the GUSTO cohort using the Sticker Delay Task. We confirmed that catch up growth interacts with IUGR, having a major role in the development of impulsivity in the first years of life and influencing inhibitory control and decision making processes.

PRS-on-Spark (PRSoS): a novel, efficient and flexible approach for generating polygenic risk scores.

BACKGROUND: Polygenic risk scores (PRS) describe the genomic contribution to complex phenotypes and consistently account for a larger proportion of variance in outcome than single nucleotide polymorphisms (SNPs) alone. However, there is little consensus on the optimal data input for generating PRS, and existing approaches largely preclude the use of imputed posterior probabilities and strand-ambiguous SNPs i.e., A/T or C/G polymorphisms. Our ability to predict complex traits that arise from the additive effects of a large number of SNPs would likely benefit from a more inclusive approach. RESULTS: We developed PRS-on-Spark (PRSoS), a software implemented in Apache Spark and Python that accommodates different data inputs and strand-ambiguous SNPs to calculate PRS. We compared performance between PRSoS and an existing software (PRSice v1.25) for generating PRS for major depressive disorder using a community cohort (N = 264). We found PRSoS to perform faster than PRSice v1.25 when PRS were generated for a large number of SNPs (~ 17 million SNPs; t = 42.865, p = 5.43E-04). We also show that the use of imputed posterior probabilities and the inclusion of strand-ambiguous SNPs increase the proportion of variance explained by a PRS for major depressive disorder (from 4.3% to 4.8%). CONCLUSIONS: PRSoS provides the user with the ability to generate PRS using an inclusive and efficient approach that considers a larger number of SNPs than conventional approaches. We show that a PRS for major depressive disorder that includes strand-ambiguous SNPs, calculated using PRSoS, accounts for the largest proportion of variance in symptoms of depression in a community cohort, demonstrating the utility of this approach. The availability of this software will help users develop more informative PRS for a variety of complex phenotypes.

The early care environment and DNA methylome variation in childhood.

Prenatal adversity shapes child neurodevelopment and risk for later mental health problems. The quality of the early care environment can buffer some of the negative effects of prenatal adversity on child development. Retrospective studies, in adult samples, highlight epigenetic modifications as sentinel markers of the quality of the early care environment; however, comparable data from pediatric cohorts are lacking. Participants were drawn from the Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) study, a longitudinal cohort with measures of infant attachment, infant development, and child mental health. Children provided buccal epithelial samples (mean age = 6.99, SD = 1.33 years, n = 226), which were used for analyses of genome-wide DNA methylation and genetic variation. We used a series of linear models to describe the association between infant attachment and (a) measures of child outcome and (b) DNA methylation across the genome. Paired genetic data was used to determine the genetic contribution to DNA methylation at attachment-associated sites. Infant attachment style was associated with infant cognitive development (Mental Development Index) and behavior (Behavior Rating Scale) assessed with the Bayley Scales of Infant Development at 36 months. Infant attachment style moderated the effects of prenatal adversity on Behavior Rating Scale scores at 36 months. Infant attachment was also significantly associated with a principal component that accounted for 11.9% of the variation in genome-wide DNA methylation. These effects were most apparent when comparing children with a secure versus a disorganized attachment style and most pronounced in females. The availability of paired genetic data revealed that DNA methylation at approximately half of all infant attachment-associated sites was best explained by considering both infant attachment and child genetic variation. This study provides further evidence that infant attachment can buffer some of the negative effects of early adversity on measures of infant behavior. We also highlight the interplay between infant attachment and child genotype in shaping variation in DNA methylation. Such findings provide preliminary evidence for a molecular signature of infant attachment and may help inform attachment-focused early intervention programs.

Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time.

Epigenome-wide association studies (EWAS) have focused primarily on DNA methylation as a chemically stable and functional epigenetic modification. However, the stability and accuracy of the measurement of methylation in different tissues and extraction types is still being actively studied, and the longitudinal stability of DNA methylation in commonly studied peripheral tissues is of great interest. Here, we used data from two studies, three tissue types, and multiple time points to assess the stability of DNA methylation measured with the Illumina Infinium HumanMethylation450 BeadChip array. Redundancy analysis enabled visual assessment of agreement of replicate samples overall and showed good agreement after removing effects of tissue type, age, and sex. At the probe level, analysis of variance contrasts separating technical and biological replicates clearly showed better agreement between technical replicates versus longitudinal samples, and suggested increased stability for buccal cells versus blood or blood spots. Intraclass correlations (ICCs) demonstrated that inter-individual variability is of similar magnitude to within-sample variability at many probes; however, as inter-individual variability increased, so did ICC. Furthermore, we were able to demonstrate decreasing agreement in methylation levels with time, despite a maximal sampling interval of only 576 days. Finally, at 6 popular candidate genes, there was a large range of stability across probes. Our findings highlight important sources of technical and biological variation in DNA methylation across different tissues over time. These data will help to inform longitudinal sampling strategies of future EWAS.

Fetal growth interacts with multilocus genetic score reflecting dopamine signaling capacity to predict spontaneous sugar intake in children.

BACKGROUND: We have shown that intrauterine growth restriction (IUGR) leads to increased preference for palatable foods at different ages in both humans and rodents. In IUGR rodents, altered striatal dopamine signaling associates with a preference for palatable foods. OBJECTIVES: Our aim was to investigate if a multilocus genetic score reflecting dopamine-signaling capacity is differently associated with spontaneous palatable food intake in children according to the fetal growth status. METHODS: 192 four-year old children from a community sample from Montreal and Hamilton, Canada, were classified according to birth weight and administered a snack test meal containing regular as well as palatable foods. Intrauterine growth restriction was based on the birth weight ratio below 0.85; children were genotyped for polymorphisms associated with dopamine (DA) signaling, with the hypofunctional variants (TaqIA-A1 allele, DRD2-141C Ins/Ins, DRD4 7-repeat, DAT1-10-repeat, Met/Met-COMT) receiving the lowest scores, and a composite score was calculated reflecting the total number of the five genotypes. Macronutrient intake during the Snack Test was the outcome. RESULTS: Adjusting for z-score BMI at 48 months and sex, there was a significant interaction of the genetic profile and fetal growth on sugar intake [߈ = -4.56, p = 0.04], showing a positive association between the genetic score and sugar intake in IUGR children, and no association in non-IUGR children. No significant interactions were seen in other macronutrients. CONCLUSIONS: Variations in a genetic score reflecting DA signaling are associated with differences in sugar intake only in IUGR children, suggesting that DA function is involved in this behavioral feature in these children. This may have important implications for obesity prevention in this population.