Regions of variable DNA methylation in human placenta associated with newborn neurobehavior.

The placenta regulates the in utero environment and functionally impacts fetal development. Candidate gene studies identified variation in placental DNA methylation is associated with newborn neurologic and behavioral outcomes including movement quality, lethargic behavior, attention, and arousal. We sought to identify novel regions of variable DNA methylation associated with newborn attention, lethargy, quality of movement, and arousal by performing an epigenome-wide association study in 335 infants from a US birth cohort.

Methylation of the Glucocorticoid Receptor (NR3C1) in Placenta Is Associated with Infant Cry Acoustics.

Epigenetic mechanisms regulating expression of the glucocorticoid receptor gene (NR3C1) promoter may influence behavioral and biological aspects of stress response in human infants. Acoustic features of infant crying are an indicator of neurobehavioral and neurological status not yet investigated in relation to epigenetic mechanisms. We examined NR3C1 methylation in placental tissue from a series of 120 healthy newborn infants in relation to a detailed set of acoustic features extracted from newborn infant cries.

Fine Motor Differences and Prenatal Serotonin Reuptake Inhibitors Exposure.

Objective: To examine fine motor differences between preschoolers with prenatal exposure to serotonin reuptake inhibitor (SRI) and children of mothers with major depressive disorder.

Study Design: A subset of children (N = 40) from a larger study on the effects of prenatal SRI and untreated major depressive disorder participated in a kinematic task of visual motor and fine motor functions at ages 4-5 years: exposure to SRI (n = 15), untreated major depressive disorder exposure (n = 10), and the control group (n = 15). The task was to reach and secure a peg, then drop it in a small hole near the start position in the light condition with full visibility or in the glow condition in which a phosphorescent peg glows in the dark.

Maternal pre-pregnancy obesity and gestational weight gain influence neonatal neurobehaviour.

Maternal weight before and during pregnancy is associated with offspring neurobehaviour in childhood. We investigated maternal weight prior to and during pregnancy in relation to neonatal neurobehaviour. We hypothesized that maternal obesity and excessive gestational weight gain would be associated with poor neonatal attention and affective functioning.

Prenatal Programming of Infant Neurobehaviour in a Healthy Population.

Background: Identifying the prenatal origins of mental conditions is of increasing interest, yet most studies have focused on high-risk populations and cannot disentangle prenatal and postnatal programming effects. Thus, we examined whether profiles of neurobehaviour indicative of future risk could be identified in healthy 1-3-day-old infants, and examined associations with perinatal risk factors.

Methods: Participants included 627 healthy mothers and term infants from a population-based US cohort.

The Contributions of Maternal Sensitivity and Maternal Depressive Symptoms to Epigenetic Processes and Neuroendocrine Functioning.

This study tested whether maternal responsiveness may buffer the child to the effects of maternal depressive symptoms on DNA methylation of NR3C1, 11β-HSD2, and neuroendocrine functioning. DNA was derived from buccal epithelial cells and prestress cortisol was obtained from the saliva of 128 infants. Mothers with depressive symptoms who were more responsive and who engaged in more appropriate touch during face-to-face play had infants with less DNA methylation of NR3C1 and 11β-HSD2 compared to mothers with depressive symptoms who were also insensitive.

School-Aged Outcomes following Prenatal Methamphetamine Exposure: 7.5-Year Follow-Up from the Infant Development, Environment, and Lifestyle Study.

Objective: To assess the relationship between prenatal methamphetamine exposure (PME) and behavior problems at age 7.5 years and the extent to which early adversity mediated this relationship.

Study Design: The multicenter, longitudinal Infant Development, Environment, and Lifestyle study enrolled 412 mother-infant pairs at 4 sites.

Neurobehavior related to epigenetic differences in preterm infants.

Unlabelled: Preterm birth is associated with medical problems affecting the neuroendocrine system, altering cortisol levels resulting in negative effects on newborn neurobehavior. Newborn neurobehavior is regulated by DNA methylation of NR3C1 and HSD11B2.

Aim: Determine if methylation of HSD11B2 and NR3C1 is associated with neurobehavioral profiles in preterm infants.

Prenatal exposure to recreational drugs affects global motion perception in preschool children.

Prenatal exposure to recreational drugs impairs motor and cognitive development; however it is currently unknown whether visual brain areas are affected. To address this question, we investigated the effect of prenatal drug exposure on global motion perception, a behavioural measure of processing within the dorsal extrastriate visual cortex that is thought to be particularly vulnerable to abnormal neurodevelopment. Global motion perception was measured in one hundred and forty-five 4.

The Roles of Maternal Depression, Serotonin Reuptake Inhibitor Treatment, and Concomitant Benzodiazepine Use on Infant Neurobehavioral Functioning Over the First Postnatal Month.

Objective: The purpose of this article was to systematically compare the developmental trajectory of neurobehavior over the first postnatal month for infants with prenatal exposure to pharmacologically untreated maternal depression, selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors (collectively: SSRIs), SSRIs with concomitant benzodiazepines (SSRI plus benzodiazepine), and no maternal depression or drug treatment (no exposure).

Method: Women (N=184) were assessed at two prenatal time points to determine psychiatric diagnoses, symptom severity, and prenatal medication usage. Infants were examined with a structured neurobehavioral assessment (Neonatal Intensive Care Unit Network Neurobehavioral Scale) at multiple time points across the first postnatal month.

Placental epigenetic patterning of glucocorticoid response genes is associated with infant neurodevelopment.

Aim: To determine associations between methylation of NR3C1, HSD11B2, FKBP5 and ADCYAP1R1 and newborn neurobehavioral outcomes.

Methods: In 537 newborns, placental methylation was quantified using bisulfite pyrosequencing. Profiles of neurobehavior were derived via the Neonatal Intensive Care Unit Network Neurobehavioral Scales.

Global motion perception is independent from contrast sensitivity for coherent motion direction discrimination and visual acuity in 4.5-year-old children.

Global motion processing depends on a network of brain regions that includes extrastriate area V5 in the dorsal visual stream. For this reason, psychophysical measures of global motion perception have been used to provide a behavioral measure of dorsal stream function. This approach assumes that global motion is relatively independent of visual functions that arise earlier in the visual processing hierarchy such as contrast sensitivity and visual acuity.

Developmental and behavioral consequences of prenatal methamphetamine exposure: A review of the Infant Development, Environment, and Lifestyle (IDEAL) study.

This study reviews the findings from the Infant Development, Environment, and Lifestyle (IDEAL) study, a multisite, longitudinal, prospective study designed to determine maternal outcome and child growth and developmental findings following prenatal methamphetamine exposure from birth up to age 7.5 years. These findings are presented in the context of the home environment and caregiver characteristics to determine how the drug and the environment interact to affect the outcome of these children.

Prenatal predictors of infant self-regulation: the contributions of placental DNA methylation of NR3C1 and neuroendocrine activity.

We examined whether placental DNA methylation of the glucocorticoid receptor gene, NR3C1 was associated with self-regulation and neuroendocrine responses to a social stressor in infancy. Placenta samples were obtained at birth and mothers and their infants (n = 128) participated in the still-face paradigm when infants were 5 months old. Infant self-regulation following the still-face episode was coded and pre-stress cortisol and cortisol reactivity was assessed in response to the still-face paradigm.

Examining the joint contribution of placental NR3C1 and HSD11B2 methylation for infant neurobehavior.

Infant neurobehavior, a potential sentinel of future mental and behavioral morbidity characterized in part by reflex symmetry, excitability and habituation to stimuli, is influenced by aspects of the intrauterine environment partially through epigenetic alterations of genes involved in the stress response. DNA methylation of two related cortisol response genes, the glucocorticoid receptor (NR3C1), a nuclear receptor to which cortisol binds, and 11-beta hydroxysteroid dehydrogenase (HSD11B2), the enzyme responsible for conversion of cortisol into inactive cortisone, independently associate with infant neurobehavior. Although these factors are part of a common cortisol regulation pathway, the combined effect of DNA methylation of these factors on infant neurobehavior has not been characterized.

Attention to the mouth and gaze following in infancy predict language development.

We investigated longitudinal relations among gaze following and face scanning in infancy and later language development. At 12 months, infants watched videos of a woman describing an object while their passive viewing was measured with an eye-tracker. We examined the relation between infants' face scanning behavior and their tendency to follow the speaker's attentional shift to the object she was describing.

Single-family room care and neurobehavioral and medical outcomes in preterm infants.

Objective: To determine whether a single-family room (SFR) NICU, including factors associated with the change to a SFR NICU, is associated with improved medical and neurobehavioral outcomes.

Methods: Longitudinal, prospective, quasi-experimental cohort study conducted between 2008 and 2012 comparing medical and neurobehavioral outcomes at discharge in infants born <1500 g. Participants included 151 infants in an open-bay NICU and 252 infants after transition to a SFR NICU.

Assessment and evaluation of the high risk neonate: the NICU Network Neurobehavioral Scale.

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus.

Placental FKBP5 genetic and epigenetic variation is associated with infant neurobehavioral outcomes in the RICHS cohort.

Adverse maternal environments can lead to increased fetal exposure to maternal cortisol, which can cause infant neurobehavioral deficits. The placenta regulates fetal cortisol exposure and response, and placental DNA methylation can influence this function. FK506 binding protein (FKBP5) is a negative regulator of cortisol response, FKBP5 methylation has been linked to brain morphology and mental disorder risk, and genetic variation of FKBP5 was associated with post-traumatic stress disorder in adults.

Physiological correlates of neurobehavioral disinhibition that relate to drug use and risky sexual behavior in adolescents with prenatal substance exposure.

Physiological correlates of behavioral and emotional problems, substance use onset and initiation of risky sexual behavior have not been studied in adolescents with prenatal drug exposure. We studied the concordance between baseline respiratory sinus arrhythmia (RSA) at age 3 and baseline cortisol levels at age 11. We hypothesized that children who showed concordance between RSA and cortisol would have lower neurobehavioral disinhibition scores which would in turn predict age of substance use onset and first sexual intercourse.

Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome.

Objective: Neonatal abstinence syndrome (NAS) from in utero opioid exposure is highly variable with genetic factors appearing to play an important role. Epigenetic changes in cytosine:guanine (CpG) dinucleotide methylation can occur after drug exposure and may help to explain NAS variability. We correlated DNA methylation levels in the mu-opioid receptor (OPRM1) promoter in opioid-exposed infants with NAS outcomes.

Attention and word learning in autistic, language delayed and typically developing children.

Previous work has demonstrated that patterns of social attention hold predictive value for language development in typically developing infants. The goal of this research was to explore how patterns of attention in autistic, language delayed, and typically developing children relate to early word learning and language abilities. We tracked patterns of eye movements to faces and objects while children watched videos of a woman teaching them a series of new words.

Effects of prenatal methamphetamine exposure on behavioral and cognitive findings at 7.5 years of age.

Objective: To examine child behavioral and cognitive outcomes after prenatal exposure to methamphetamine.

Study Design: We enrolled 412 mother-infant pairs (204 methamphetamine-exposed and 208 unexposed matched comparisons) in the Infant Development, Environment, and Lifestyle study. The 151 children exposed to methamphetamine and 147 comparisons who attended the 7.

Reactivity and regulation of motor responses in cocaine-exposed infants.

Unlabelled: Effects of prenatal exposure to cocaine on the reactivity and regulation of the motor system of 825 four-month-old infants enrolled in the Maternal Lifestyle Study were examined. Videotaped assessments of 338 cocaine-exposed (CE) infants and 487 non-exposed comparison infants were coded by examiners masked to exposure status. Exposure status was determined by meconium assay and maternal self-report of prenatal cocaine use.