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Our primary objective was to document COVID-19 induced changes to perinatal care across the USA and examine the implication of these changes for maternal mental health. We performed an observational cross-sectional study with convenience sampling using direct patient reports from 1918 postpartum and 3868 pregnant individuals collected between April 2020 and December 2020 from 10 states across the USA. We leverage a subgroup of these participants who gave birth prior to March 2020 to estimate the pre-pandemic prevalence of specific birthing practices as a comparison. Our primary analyses describe the prevalence and timing of perinatal care changes, compare perinatal care changes depending on when and where individuals gave birth, and assess the linkage between perinatal care alterations and maternal anxiety and depressive symptoms. Seventy-eight percent of pregnant participants and 63% of postpartum participants reported at least one change to their perinatal care between March and August 2020. However, the prevalence and nature of specific perinatal care changes occurred unevenly over time and across geographic locations. The separation of infants and mothers immediately after birth and the cancelation of prenatal visits were associated with worsened depression and anxiety symptoms in mothers after controlling for sociodemographic factors, mental health history, number of pregnancy complications, and general stress about the COVID-19 pandemic. Our analyses reveal widespread changes to perinatal care across the US that fluctuated depending on where and when individuals gave birth. Disruptions to perinatal care may also exacerbate mental health concerns, so focused treatments that can mitigate the negative psychiatric sequelae of interrupted care are warranted.

Objective: Single-substance exposure effects on neurodevelopmental outcomes, such as problem behavior and intelligence quotient (IQ), have been studied in children for decades. However, the long-term consequences of polysubstance exposure are poorly understood. Study Design: Longitudinal neurodevelopmental data were gathered from cohorts across the United States (U.S.) through the Environmental influences on Child Health Outcomes (ECHO) Program. Data on prenatal exposure to opioids, nicotine, marijuana, and alcohol were collected from children ages 6-11 years (N=256). Problem behavior was assessed using the Child Behavior Checklist (school-age version, CBCL-Sch), and verbal IQ (VIQ) and performance IQ (PIQ) were assessed using the Weschler Intelligence Scale for Children, Fifth Edition (WISC-5). We first identified latent profiles in the overall sample, then evaluated differences in profile membership for children with and without prenatal substance exposure. Results: Latent profile analysis identified two mutually exclusive categories: average VIQ and PIQ, with typical problem behavior; and below-average VIQ with average PIQ and clinically significant problem behavior. Children with prenatal nicotine and polysubstance exposures were more likely to be classified in the below-average VIQ, elevated problem behavior profile compared with children without prenatal nicotine exposure. Conclusions: The presence of clinically significant behavior problems in children with average PIQ, but below-average VIQ, could represent a unique endophenotype related to prenatal nicotine exposure in the context of other prenatal substance exposures.

The dynamics of parent-infant physiology are essential for understanding how biological substrates of emotion regulation are organized during infancy. Although parent-infant physiological processes are dyadic in nature, research is limited in understanding how one person’s physiological responses predict one’s own and as well as the other person’s responses in the subsequent moment. In this study, we examined mother-infant respiratory sinus arrhythmia (RSA) dynamics during the Still-Face Paradigm (SFP) among 106 mothers (M(age) = 29.54) and their 7-month-old infants (55 males). Given mothers’ role in shaping dyadic interactions with their infant, we also tested how mothers’ self-reported emotion dysregulation (measured via the Difficulties in Emotion Regulation Scale) associated with these dynamics. Results showed that both mothers’ and infants’ RSA tended to return to their respective homeostatic points (i.e., exhibited return strength) during each SFP episode, indicating stability in RSA for mother-infant dyads. Significant shifts in mother and infant RSA return strength were observed across SFP episodes, highlighting the role of contextual demands on each individual’s physiological dynamics. Mother-infant RSA dynamics varied as a function of maternal self-reported emotion dysregulation. Specifically, RSA levels of infants with more dysregulated mothers had a weaker tendency to return to homeostasis during the Reunion episode and were less affected by their mothers’ RSA during the Still-Face and Reunion episodes of the SFP, suggesting a less effective coregulatory influence. Our findings have implications for the intergenerational transmission of emotion dysregulation via mother-infant physiological dynamics.

Pregnant women struggling with emotion dysregulation may be more likely to engage in a wide range of health risk behaviors. This protocol describes a study on intergenerational transmission of emotion dysregulation from the third trimester of pregnancy to 18 months postpartum. Biobehavioral markers of emotion dysregulation are typically measured in laboratory settings which was prohibited by many universities during the COVID-19 pandemic. We describe how markers of emotion dysregulation (e.g. maternal, fetal, and infant heart rate variability) are collected remotely. We detail how data collection can be augmented to reach diverse populations who may not otherwise participate in laboratory-based research.

Paternal stress is often assessed by maternal report and is posited to influence infant development indirectly by contributing to a mother's stress and experiences during pregnancy. Far less is known about how direct effects of prenatal paternal stress, as described by fathers themselves, are related to an infant's physiological functioning. We assessed fathers' own experiences of stress and examined its direct impact on infant respiratory sinus arrhythmia (RSA), a biological index of self-regulation, at seven-month postpartum.During the third trimester of pregnancy, the UCLA Life Stress Interview was conducted to assess chronic stress in mothers and fathers (Infants of fathers with high prenatal stress showed lower baseline RSA, possibly reflective of poor infant psychophysiological regulation. The predictive role of paternal stress remained significant after controlling for maternal stress.Our findings provide emerging empirical evidence to support the influence of prenatal paternal stress on infant RSA, highlighting the important role of fathers for child development.

The development of personality pathology is an interactive process between biologically-based susceptibilities, interpersonal patterns, and contextual factors across the lifespan. In this paper, we argue that these interactions begin before birth. We describe the perinatal period (i.e., pregnancy and up to one year postpartum) as a sensitive developmental window during which regulatory and stress response systems that confer risk for personality pathology begin forming. In addition, we present converging evidence for significant associations between perinatal factors and later life personality disorders. Finally, we present this perinatal perspective through the lens of dynamical systems theory and emphasize the promise of this framework for guiding future personality disorder research, prevention, and intervention.

This study tested whether newborn attention and arousal provide a foundation for the dynamics of respiratory sinus arrhythmia (RSA) in mother–infant dyads. Participants were 106 mothers (M(age) = 29.54) and their 7-month-old infants (55 males and 58 White and non-Hispanic). Newborn attention and arousal were measured shortly after birth using the NICU Network Neurobehavioral Scale. Higher newborn arousal predicted a slower return of infant RSA to baseline. Additionally, greater newborn attention predicted mothers’ slower return to baseline RSA following the still-face paradigm, and this effect only held for mothers whose infants had lower newborn arousal. These findings suggest that newborn neurobehavior, measured within days of birth, may contribute to later mother–infant physiological processes while recovering from stress.

To examine postpartum depressive symptom trajectories from birth to age 5 and their risk factors in a national sample of mothers of preterm and full-term infants. The racially and ethnically diverse sample comprised 11,320 maternal participants (M

Prenatal intrauterine exposures and postnatal caregiving environments may both shape the development of infant parasympathetic nervous system (PNS) activity. However, the relative contributions of prenatal and postnatal influences on infant respiratory sinus arrhythmia (RSA)–an index of PNS functioning–are relatively unknown. We examined whether prenatal and postnatal maternal emotion dysregulation, a transdiagnostic construct that spans mental health diagnoses, were independently related to infant RSA trajectories during a social stressor, the still-face paradigm. Our sample included 104 mothers and their 7-month-old infants. Maternal emotion dysregulation was measured with the Difficulties in Emotion Regulation Scale during the 3rd trimester of pregnancy and again at a 7-month postpartum laboratory visit. Infant RSA was recorded during the still-face paradigm. Only postnatal maternal emotion dysregulation was associated with infant RSA. Specifically, high postnatal emotion dysregulation was associated with a blunted (i.e., dampened reactivity and recovery) infant RSA response profile. Infant sex did not moderate the associations between maternal emotion dysregulation and infant RSA. Findings suggest that postnatal interventions to promote effective maternal emotion regulation may reduce risk for infants’ dysregulated psychophysiological stress responses.

Significant racial health disparities in infant mortality, preterm birth, and infant neurodevelopment exist in the United States. These disparities highlight a critical public health problem: Children of color are at a developmental disadvantage before birth. In this article, we describe how pregnant women from marginalized communities are disproportionately more likely to experience chronic stress in the form of discrimination, historical trauma, and acculturation. We integrate these understudied forms of chronic stress into allostatic load and prenatal programming models to describe how they can affect the health of two generations: the pregnant woman and her child. We describe psychophysiological ramifications of this early-life stress in infants of color. The prenatal programming field has largely ignored the experiences of women of color, and we highlight the need for researchers to include, or focus exclusively on, diverse samples in their research to reduce disparities that are evident at birth.

In 2010, the Research Domain Criteria (RDoC) were developed to advance our understanding of the pathophysiology of mental illness across multiple levels of analysis, ranging from cells to circuits to self-report instruments. Several conceptual RDoC-informed manuscripts have highlighted the importance of studying how developmental processes give rise to psychopathology. However, there are few empirical studies that integrate the RDoC framework with development and psychopathology principles. This special issue was developed to fill this empirical gap. In this introduction to the special issue, we describe how the developmental psychopathology field predates and informs the RDoC framework. We highlight three important ways in which developmental psychopathology and the RDoC framework can mutually inform one another, leading to novel discoveries to identify, prevent, and treat mental health problems across the life span.

This study tested two competing models of differential susceptibility and diathesis-stress in a prospective longitudinal study of African American youths (N = 935). It examined whether individual variations in the functioning of the hypothalamic-pituitary-adrenocortical axis at age 11 interact with middle childhood parent-child relationship quality to predict mental and physical health problems in adolescence (ages 11-15 years old). Adolescent boys with lower levels of cortisol reactivity to laboratory challenges had the highest levels of internalizing problems if they experienced a high conflictual relationship with their parents. Equally low-reactive boys, however, reported the lowest number of physical illnesses if their relationship with their parents was characterized by high levels of intimacy and support.

We investigated whether neurobehavioral markers of risk for emotion dysregulation were evident among newborns, as well as whether the identified markers were associated with prenatal exposure to maternal emotion dysregulation. Pregnant women (N= 162) reported on their emotion dysregulation prior to a laboratory assessment. The women were then invited to the laboratory to assess baseline respiratory sinus arrhythmia (RSA) and RSA in response to an infant cry. Newborns were assessed after birth via the NICU Network Neurobehavioral Scale. We identified two newborn neurobehavioral factors—arousal and attention—via exploratory factor analysis. Low arousal was characterized by less irritability, excitability, and motor agitation, while low attention was related to a lower threshold for auditory and visual stimulation, less sustained attention, and poorer visual tracking abilities. Pregnant women who reported higher levels of emotion dysregulation had newborns with low arousal levels and less attention. Larger decreases in maternal RSA in response to cry were also related to lower newborn arousal. We provide the first evidence that a woman's emotion dysregulation while pregnant is associated with risks for dysregulation in her newborn. Implications for intergenerational transmission of emotion dysregulation are discussed.

Children with prenatal substance exposure are at increased risk for externalizing behavior problems and violence. However, the contribution of early life experiences for placing these individuals at risk is not well understood. Utilizing a sample of 1,388 children with prenatal substance exposure from the Maternal Lifestyle Study, we attempt to shed light on these contributing factors by examining the impact of infant temperament, maternal sensitivity, and early life stress on the expression of violent behavior at ages 12 through 14 years. Males may be more at risk for increases in violent behavior in early adolescence through a number of early life experiences, such as variability in responses to maternal flexibility and engagement related to individual differences in temperament, as well as exposure to early adversity. Comparing two prevailing developmental theoretical frameworks, deficit models and differential susceptibility, we aim to understand the developmental origins of violent behavior in males by identifying children who may be most susceptible to early caregiving experiences.

A growing body of neurobiological and psychological research sheds light on the mechanisms underlying the development and maintenance of opioid use disorder and its relation to maladaptive parenting. Perinatal opioid use is associated with significant maternal distress, as well as increased risk for child maltreatment and impaired developmental outcomes for children. Drawing from extant data, here we provide an integrated mechanistic model of perinatal opioid use, parenting behavior, infant attachment, and child well-being to inform the development and adaptation of behavioral interventions for opioid-exposed mother-infant dyads. The model posits that recurrent perinatal opioid use leads to increased stress sensitivity and reward dysregulation, resulting in decreased perceived salience of infant cues, disengaged parenting behavior, disrupted infant attachment, and decreased child well-being. We conclude with a discussion of Mindfulness-Oriented Recovery Enhancement as a means of addressing pathogenic mechanisms undergirding perinatal opioid use, maladaptive parenting, and attachment deficits, presenting evidence on the efficacy and therapeutic mechanisms of mindfulness. As perinatal opioid use increases in the United States, empirically-informed models can be used to guide treatment development research and address this growing concern.

We examined whether Research Domain Criteria (RDoC)-informed measures of prenatal stress predicted newborn neurobehavior and whether these effects differed by newborn sex. Multilevel, prenatal markers of prenatal stress were obtained from 162 pregnant women. Markers of the Negative Valence System included physiological functioning (respiratory sinus arrhythmia [RSA] and electrodermal [EDA] reactivity to a speech task, hair cortisol), self-reported stress (state anxiety, pregnancy-specific anxiety, daily stress, childhood trauma, economic hardship, and family resources), and interviewer-rated stress (episodic stress, chronic stress). Markers of the Arousal/Regulatory System included physiological functioning (baseline RSA, RSA, and EDA responses to infant cries) and self-reported affect intensity, urgency, emotion regulation strategies, and dispositional mindfulness. Newborns’ arousal and attention were assessed via the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale. Path analyses showed that high maternal episodic and daily stress, low economic hardship, few emotion regulation strategies, and high baseline RSA predicted female newborns’ low attention; maternal mindfulness predicted female newborns’ high arousal. As for male newborns, high episodic stress predicted low arousal, and high pregnancy-specific anxiety predicted high attention. Findings suggest that RDoC-informed markers of prenatal stress could aid detection of variance in newborn neurobehavioral outcomes within hours after birth. Implications for intergenerational transmission of risk for psychopathology are discussed.

There is limited understanding of factors across the lifespan that influence pregnant women's respiratory sinus arrhythmia (RSA), which could have implications for their health and offspring development. We examined associations among 162 English- and Spanish-speaking pregnant women's childhood maltreatment history, emotion dysregulation, recent life stress, and resting RSA during the third trimester. Moderated mediation analyses indicated that more severe childhood maltreatment history (95% confidence interval (CI) [0.26, 0.63]) and higher emotion dysregulation (95% CI [0.001, 0.006]) predicted more stress during pregnancy, and childhood maltreatment history interacted with emotion dysregulation to predict resting RSA (95% CI [-0.04, -0.0003]). Exploratory analyses revealed that women's health-related stress during pregnancy mediated the relation between emotion dysregulation and RSA regardless of childhood maltreatment severity (95% CI [-0.007, -0.002]). These findings suggest that women's resting RSA during pregnancy may reflect physical and emotional stress accumulation across the lifespan and that relations between early life adversity and prenatal psychophysiology may be buffered by protective factors, such as emotion regulation. In addition, these findings underscore the importance of distinguishing between types of prenatal stress. Given the implications for women's health and offspring development, we urge researchers to continue exploring factors associated with pregnant women's psychophysiology.

Newborn neurobehavioral competencies portend a young child’s abilities to modulate their arousal and attention in response to dynamic environmental cues. Although evidence suggests prenatal contributions to newborn neurobehavioral differences, no study to date has examined wellness-promoting traits, such as a pregnant woman’s mindfulness, in this association. We examined whether a mother’s mindfulness while pregnant related to neurobehavioral outcomes in her neonate, as well as whether maternal mindfulness moderated the link between prenatal maternal emotion dysregulation and newborn neurobehavior. Mothers (N = 162) reported on their mindfulness and emotion dysregulation while pregnant. Newborn arousal and attention were assessed at least 24 hours after birth (M = 3.8 days, SD = 8.3) using the NICU Network Neurobehavioral Scale (NNNS). Highly mindful pregnant women reported lower levels of emotion dysregulation. Newborns of highly mindful mothers exhibited higher levels of arousal (e.g., excitability, motor activity), but did not differ in regards to attention at birth. Maternal emotion dysregulation while pregnant was associated with blunted newborn attention, but only among mothers who were less mindful. Our findings suggest that a mother’s mindfulness while pregnant may influence her fetus’ neurobehavioral development in ways that are evident at birth.

Background: Adequate perinatal care is essential for maternal and infant health. The novel coronavirus (COVID-19) pandemic is potentially the largest natural disruption to perinatal care in recent history, but these disruptions have yet to be characterized in a rigorous and systematic manner. Our goal was to document COVID-19 induced disruptions to perinatal care across the United States (US) using analyses sensitive to the temporal and geographical variability of the pandemic, and to examine the impact of these healthcare disruptions on maternal mental health. Methods: We performed an observational cross-sectional study of 1,922 postpartum and 3,868 pregnant individuals during the 2020 COVID-19 pandemic. Perinatal individuals were recruited from 15 academic institutions across the US, resulting in a geographically diverse sample. We conducted (1) descriptive analyses on the prevalence and timing of perinatal care disruptions, (2) group difference analyses to compare perinatal care disruptions depending on when and where individuals gave birth, (3) cross correlations to assess the temporal linkage between perinatal care disruptions and COVID-19 infection rates, and (4) hierarchical linear regressions to evaluate the impact of prenatal care and birth protocol disruptions on maternal psychological health. Findings: The COVID-19 pandemic significantly altered perinatal care across the US, both through restriction of in-person support and by shifting the focus of care. These changes occurred unevenly over time and across geographic locations. Changes in COVID-19 infection rates explained 65 to 78% of the variance in perinatal care disruptions from August 2019 to August 2020. Moreover, disruptions to perinatal care were robustly associated with heightened psychological distress in mothers, even after controlling for mental health history, number of pregnancy complications, and general stress about the COVID-19 pandemic. Interpretation: Our analyses reveal widespread disruptions to perinatal care across the US that fluctuated depending on where and when individuals gave birth, demonstrating reactivity and elasticity of the US healthcare system. In addition to influencing health outcomes, disruptions to perinatal care may also exacerbate mental health concerns during the COVID-19 pandemic. Funding Information: This research was supported by the NYU COVID-19 Research Catalyst rant, R34DA050287-S1, R34DA050287-S2, R34DA050254-01S2, R01MH126468, R01MH125870, the Nathaniel Wharton Fund, the Columbia University Population Research Center, R34DA050255, R34DA050255-01S2, the Fralin Biomedical Research Institute at VTC, the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers UL1TR003015 and KL2TR003016, the University of Utah Center for Clinical and Translational Science COVID-19 Research Award, Virginia Commonwealth University School of Nursing Internal Grants Program, Sarah P. Farrell Legacy Research Endowment-Virginia Commonwealth University, 5R03HD096141-02, R01HD085990, R34DA050283-01S2, the USC Center for the Changing Family, the Stanford Institute for Research in the Social Sciences, R34DA050291, R01MH119070, R01MH117177, R34 DA050272-01S1, R01 MH113883, R01 DA046224, R21 MH111978, and R21 HD090493, R37 MH10149, UH3OD023279, and National Center for Advancing Translational Sciences (NCATS) Grant UL1TR001881 Declaration of Interests: The authors report no conflicts of interest. Ethics Approval Statement: This study has received Institutional Review Board approval from theNYU Langone Health IRB as well as the local IRBs at each data collection site. All data was collected in accordance with the Helsinki Declaration.

Introduction Pre-sleep arousal contributes to over 50% of pregnant people experiencing poor sleep quality and clinical insomnia. Given that poor sleep during pregnancy is associated with depression and suicide ideation, there is a critical need to identify intervention targets, such as difficulties with emotion regulation. However, emotion dysregulation is multifaceted and warrants further investigation in sleep research, particularly during pregnancy. Thus, the present study examined associations among pre-sleep arousal, various dimensions of emotion dysregulation, and sleep outcomes during pregnancy. Methods Participants (N = 62; Mage = 29.89, SD = 4.19 years) were recruited during pregnancy and enrolled to represent a range of scores on the Difficulties in Emotion Regulation Scale. For 7 days during the 3rd trimester, they wore CamNtech MotionWatch-8 wrist actigraphs and completed the Pre-Sleep Arousal Scale and Consensus Sleep Diary. Results Hierarchical linear regression analyses indicated that high pre-sleep arousal predicted low sleep efficiency (measured via actigraphy) above and beyond facets of emotion dysregulation (B = -.316, p = .026). High pre-sleep arousal also predicted poor sleep quality (measured via diary) above and beyond total emotion dysregulation (B = -.038, p = .010). However, an interaction emerged between pre-sleep arousal and one particular facet of emotion dysregulation: access to emotion regulation strategies (B = -.005, p = .023). Specifically, high pre-sleep arousal was associated with poor sleep quality only among those who reported limited abilities to use emotion regulation strategies. Among participants who reported that they could access effective emotion regulation strategies, pre-sleep arousal did not predict sleep quality. Conclusion This study indicates that high pre-sleep arousal may not always be associated with poor sleep quality during pregnancy. Equipping pregnant people with emotion regulation strategies may buffer this association and promote long-term health. It is recommended that perinatal sleep scientists continue investigating relations between facets of emotion dysregulation and sleep. Support (If Any) This project was supported by the National Institute of Mental Health under Awards R01MH119070 (MPIs Crowell & Conradt) and F31MH124275 (PI Kaliush). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH.

Across a range of challenging contexts, a complex system of stress responses within multiple domains (e.g., behavior, physiology) support, or thwart, an infant's capacity to navigate an ever-changing world. As understanding of these individual stress response systems has improved, researchers have called for integrated examinations across multiple systems and domains. However, extant research has usually focused on reactivity within a single system and very few explore the associations between multiple domains of stress responding. Drawing on a diverse sample of 135 mother-infant dyads, the current study explored biobehavioral concordance across the Autonomic Nervous System (ANS; measured via both cardiac and salivary indicators), Hypothalamic-pituitary-adrenal (HPA; measured via salivary indicators) axis, observed behavior, and maternal reports of temperament. Correlation analysis generally revealed moderate negative associations between ANS and HPA axis, moderate negative associations between ANS and coded negative behavior, and small-to-moderate positive associations between ANS and coded object engagement and social behavior. Salivary biomarkers and maternal report of infant temperament showed less concordance across systems and domains than cardiac ANS indicators. These findings provide a foundational understanding of the associations between biobehavioral indicators of stress responses in infancy, a period of high developmental plasticity.

Decades of fetal programming research indicates that we may be able to map the origins of many physical, psychological, and medical variations and morbidities before the birth of the child. While great strides have been made in identifying associations between prenatal insults, such as undernutrition or psychosocial stress, and negative developmental outcomes, far less is known about how adaptive responses to adversity regulate the developing phenotype to match stressful conditions. As the application of epigenetic methods to human behavior has exploded in the last decade, research has begun to shed light on the role of epigenetic mechanisms in explaining how prenatal conditions shape later susceptibilities to mental and physical health problems. In this review, we describe and attempt to integrate two dominant fetal programming models: the cumulative stress model (a disease-focused approach) and the match–mismatch model (an evolutionary–developmental approach). In conjunction with biological sensitivity to context theory, we employ these two models to generate new hypotheses regarding epigenetic mechanisms through which prenatal and postnatal experiences program child stress reactivity and, in turn, promote development of adaptive versus maladaptive phenotypic outcomes. We conclude by outlining priority questions and future directions for the fetal programming field.

Following recent advances in behavioral and psychiatric epigenetics, researchers are increasingly using epigenetic methods to study prenatal exposure to maternal mood disorder and its effects on fetal and newborn neurobehavior. Despite notable progress, various methodological limitations continue to obscure our understanding of the epigenetic mechanisms underpinning prenatal exposure to maternal mood disorder on newborn neurobehavioral development. Here we detail this problem, discussing limitations of the currently dominant analytical approaches (i.e., candidate epigenetic and epigenome-wide association studies), then present a solution that retains many benefits of existing methods while minimizing their shortcomings: epigenetic pathway analysis. We argue that the application of pathway-based epigenetic approaches that target DNA methylation at transcription factor binding sites could substantially deepen our mechanistic understanding of how prenatal exposures influence newborn neurobehavior.

Prenatal programming models have rarely been applied to research on children with prenatal substance exposure, despite evidence suggesting that prenatal drug exposure is a form of stress that impacts neurodevelopmental outcomes and risk for psychopathology. Utilizing data from two longitudinal multisite studies comprising children prenatally exposed to substances as well as a nonexposed comparison group (Maternal Lifestyle Study, n = 1,388; Infant Development, Environment, and Lifestyle study, n = 412), we tested whether early phenotypic indicators of hypothesized programming effects, indexed by growth parameters at birth and infant temperament, served as a link between prenatal substance exposure and internalizing and externalizing behavior at age 5. Latent profile analysis indicated that individual differences in reactivity and regulation for infants prenatally exposed to substances was best characterized by four temperament profiles. These profiles were virtually identical across two independent samples, and demonstrated unique associations with adjustment difficulties nearly 5 years later. Results of path analysis using structural equation modeling also showed that increased prenatal substance exposure was linked to poorer growth parameters at birth, profiles of temperamental reactivity in infancy, and internalizing and externalizing behavior at age 5. This pathway was partially replicated across samples. This study was among the first to link known individual-level correlates of prenatal substance exposure into a specific pathway to childhood problem behavior. Implications for the developmental origins of a child's susceptibility to psychopathology as a result of intrauterine substance exposure are discussed.

AIM To describe neurobehavioral patterns in neonates with congenital heart disease (CHD). METHOD A cohort study describing neurobehavioral performance of neonates with CHD requiring cardiac surgery. The neonates were evaluated preoperatively and postoperatively with the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) and scores were compared with published normative values. Clinical factors were obtained by chart review to assess their association with behavior. The CHD NNNS score pattern was compared with previously reported profiles in other high-risk populations. RESULTS NNNS evaluations were completed on 67 neonates with CHD, resulting in 97 evaluations (50 preoperative, 47 postoperative). Compared with normative values, the cohort with CHD demonstrated decreased attention, regulation, asymmetry, stress, arousal, and excitability, along with increased non-optimal reflexes, lethargy, and need for handling (p

While the negative effects of early-life stress on children’s developmental outcomes are well documented, we know little about how these processes unfold and which children are more susceptible to these exposures. In this article, I outline how studying the effects of early-life stress on children’s development can be advanced by considering how epigenetic processes may contribute to the emergence of children’s behavior. The study of epigenetics can help pinpoint the mechanisms by which early-life stress may affect developmental outcomes and identify which children may be most sensitive to the effects of these exposures. I conclude by highlighting the challenges inherent in studying epigenetics in children and offer possible solutions.

Neonatal opioid withdrawal syndrome (NOWS) has risen in prevalence from 1.2 per 1000 births in 2000 to 5.8 per 1000 births in 2012. Symptoms in neonates may include high-pitched cry, tremors, feeding difficulty, hypertonia, watery stools, and breathing problems. However, little is known about the neurodevelopmental consequences of prenatal opioid exposure in infancy, early childhood, and middle childhood. Even less is known about the cognitive, behavioral, and academic outcomes of children who develop NOWS. We review the state of the literature on the neurodevelopmental consequences of prenatal opioid exposure with a particular focus on studies in which NOWS outcomes were examined. Aiming to reduce the incidence of prenatal opioid exposure in the near future, we highlight the need for large studies with prospectively recruited participants and longitudinal designs, taking into account confounding factors such as socioeconomic status, institutional variations in care, and maternal use of other substances, to independently assess the full impact of NOWS. As a more immediate solution, we provide an agenda for future research that leverages the National Institutes of Health Environmental Influences on Child Health Outcomes program to address many of the serious methodologic gaps in the literature, and we answer key questions regarding the short- and long-term neurodevelopmental health of children with prenatal opioid exposure.

Caregivers play a critical role in scaffolding infant stress reactivity and regulation, but the mechanisms by which this scaffolding occurs is unclear. Animal models strongly suggest that epigenetic processes, such as DNA methylation, are sensitive to caregiving behaviors and, in turn, offspring stress reactivity. We examined the direct effects of caregiving behaviors on DNA methylation in infants and infant stress reactivity. Infants and mothers (N = 128) were assessed during a free play when infants were 5 months old. Maternal responsiveness and appropriate touch were coded. and infant buccal epithelial cells were sampled to assess for DNA methylation of the glucocorticoid receptor gene, NR3c1 exon 1F. Infant cortisol reactivity was assessed in response to the still-face paradigm. Greater levels of maternal responsiveness and appropriate touch were related to less DNA methylation of specific regions in NR3c1 exon 1F, but only for females. There was no association with maternal responsiveness and appropriate touch or DNA methylation of NR3c1 exon 1F on prestress cortisol or cortisol reactivity. Our results are discussed in relation to programming models that implicate maternal care as an important factor in programing infant stress reactivity.Los cuidadores juegan un papel esencial en el andamiaje de la reactividad y regulación del estrés infantil pero los mecanismos por medio de los cuales aparece este andamiaje no están claros. Los modelos animales fuertemente sugieren que los procesos epigenéticos, tales como la metilación del ADN, son sensibles a los comportamientos de prestaciones de cuidado y por consiguiente a la reactividad al estrés por parte de los hijos. Examinamos los efectos directos que los comportamientos de prestaciones de cuidado tienen sobre la metilación de ADN en infantes y, por consiguiente, la reactividad del estrés infantil. Los infantes y sus madres (N = 128) fueron evaluados durante una sesión de juego libre cuando los infantes tenían 5 meses de edad. Se codificó la sensibilidad materna y la apropiada forma de tocar y se obtuvo muestra de las células epiteliales bucales del infante para analizar la metilación de ADN del gen receptor glucocorticoide, NR3c1, exón 1F. Se evaluó la reactividad del infante al cortisol como respuesta al paradigma de la cara quieta. Niveles mayores de sensibilidad materna y apropiada forma de tocar se relacionaron con menos metilación de ADN de regiones específicas en NR3c1 exón 1F, aunque sólo en las niñas. No se presentó ninguna asociación con la sensibilidad materna y la apropiada forma de tocar, o metilación de ADN de NR3c1 exón 1F en el cortisol pre-estrés o la reactividad del cortisol. Nuestros resultados se discuten en relación con modelos de programación que implican cuidado materno como un importante factor en la programación de la reactividad del estrés del infante.Les personnes prenant soin des enfants jouent un rôle critique dans l’échafaudage de la réaction au stress du nourrisson et la régulation mais les mécanismes selon lesquels cet échafaudage se bâtit ne sont pas clairs. Les modèles animaux suggèrent fortement que des processus épigénétiques, comme la méthylation de l'ADN, sont sensibles au comportements de qui prend soin d'eux et en conséquence déclenchent un réaction au stress. Nous avons examiné les effets directs des comportements soignants sur la méthylation de l'ADN chez les bébés, en ensuite sur la réaction au stress du nourrisson. Des nourrissons et leurs mères (N = 128) ont été évalués au moyen d'un jeu libre quand les bébés avaient 5 mois d’âge. La réaction maternelle et le toucher approprié ont été codés et des cellules épithéliales buccales du bébé ont été prélevées afin d’évaluer la méthylation de l'ADN du gène récepteur glucocorticoïde, le NR3c1 exon 1F. La réaction du cortisol du bébé a été évaluée en réponse au paradigme du visage immuable. Des niveaux plus élevés de réaction maternelle et de toucher approprié étaient liés à une méthylation de l'ADN des régions spécifiques de NR3c1 exon 1F moindre, mais seulement chez les filles. On n'a trouvé aucun lien avec la réaction maternelle et le toucher approprié ou de méthylation NR3c1 exon 1F de l'ADN sur le cortisol pré-test ou de réaction du cortisol. Nos résultats sont discutés en relation aux modèles de programme qui impliquent que le soin maternel en tant que facteur important dans la programmation de la réaction au stress du bébé.Die Bezugspersonen spielen eine entscheidende Rolle für die Herausbildung der Reaktionsfähigkeit und Regulierung von Säuglingen, aber die Mechanismen, wie diese entstehen, sind unklar. Tiermodelle deuten stark darauf hin, dass epigenetische Prozesse, wie z.B. die DNA-Methylierung, sensitiv auf das Verhalten der Bezugspersonen reagieren und wiederum die Reaktivität der Nachkommen beeinflussen. Wir untersuchten die direkten Auswirkungen des Verhaltens der Bezugspersonen auf die DNA-Methylierung bei Säuglingen und damit wiederum auf die Stressreaktivität von Säuglingen. Säuglinge und Mütter (N = 128) wurden während eines freien Spiels im Alter von 5 Monaten beurteilt. Die mütterliche Responsivität und die entsprechende Berührung wurden kodiert und bukkale Epithelzellen von Säuglingen wurden untersucht, um die DNA-Methylierung des Glukokortikoid-Rezeptorgens NR3c1-Exon 1F zu beurteilen. Die Reaktivität des Säuglings auf Cortisol wurde als Antwort auf das Still-Face-Paradigma bewertet. Ein höheres Ausmaß an mütterlicher Responsivität und passenden Berührungen waren mit einer geringeren DNA-Methylierung bestimmter Regionen im NR3c1-Exon 1F verbunden, jedoch nur für das weibliche Geschlecht. Es gab keinen Zusammenhang für die mütterliche Responsivität und passende Berührungen oder DNA-Methylierung des NR3c1-Exons 1F mit der Reaktivität von Cortisol oder dem Cortisol vor der Belastung. Unsere Ergebnisse werden in Bezug auf Programmiermodelle diskutiert, die die mütterliche Fürsorge als einen wichtigen Faktor bei der Programmierung der Stressreaktivität von Säuglingen beinhalten.乳幼児期のNR3c1のＤＮＡメチル化:母親の養育と乳幼児の性別の関連 養育者は乳幼児のストレス反応性と調節の土台に大切な役割を果たすが、この土台が生じるメカニズムは明らかでない。動物モデルはＤＮＡメチル化のような、養育行動や、子どものストレス反応性に敏感である後成的なプロセスを強く示唆する。我々は養育行動が乳幼児のＤＮＡメチル化と、乳幼児のストレス反応性に直接与える影響を検討した。乳幼児が 5 ヶ月のとき、乳幼児と母親 （N=128） を自由遊び中に評価した。母親の応答性と適切な接触をコード化し、糖質コルチコイド受容体遺伝子である NR3cI エクソン 1F の DNA メチル化を評価するために乳幼児の頬粘膜細胞を標本抽出した。乳幼児のコルチゾール反応性は still face の反応性パラダイムに応じて評価した。より大きなレベルの母親の反応性と適切な接触は、 NR3cI エクソン 1F の特定領域の DNA メチル化に関連が少なかったが、それは女児だけにあてはまった。母親の反応性と適切な接触もしくは NR3cI エクソン 1F の DNA メチル化と、ストレス前のコルチゾールやコルチゾール反応性との関連は認めなかった。我々の研究結果を母親の養育が、乳幼児のストレス反応性のプログラミングにおける重要な因子であると示唆するプログラミングモデルとの関連から議論する。.嬰兒期NR3c1的DNA甲基化:母親照顧與兒童性別的關係 護理人員在支架嬰兒對壓力反應和調節方面發揮著關鍵作用， 但這種支架發生的機制尚不清楚。動物模型強烈表明， 表觀遺傳過程， 如 DNA 甲基化， 對護理行為和後代壓力反應敏感。我們檢查護理行為對嬰兒 DNA 甲基化的直接影響， 進而檢測嬰兒對壓力反應。當嬰兒 5 個月大時， 在自由遊戲期間評估嬰兒和母親 （N = 128）。對母體反應性和適當的觸覺進行編碼， 並對嬰兒頰上皮細胞進行取樣， 以評估糖皮質激素受體基因 NR3c1 外顯子 1F 的 DNA 甲基化。評估嬰兒皮質醇反應性以響應靜止面觀範例。較高水平的母體反應性和適當的觸覺， 與 NR3c1 外顯子1F中特定區域的較少 DNA 甲基化相關， 但僅限於女嬰。母親反應和適當接觸或 NR3c1 外顯子 1F 的 DNA 甲基化， 與壓力前皮質醇或皮質醇反應性無關。我們討論結果與編程模型的關係， 這些編程模型將孕產婦護理作為影響嬰兒對壓力反應的重要因素。.ميثيل الحمض النووي لNR3c1 في مرحله الرضاعة: الارتباطات بين رعاية الامومة وجنس الرضع مقدمو الرعاية يلعبون دورا حاسما في تدعيم استجابة الرضع للإجهاد والتنظيم ولكن الآليات التي يحدث بها هذا التدعيم غير واضحة. النماذج الحيوانية تشير بقوة إلى ان العمليات الوراثية ، مثل ميثيل الحمض النووي ، حساسة لسلوكيات الرعاية وبدورها تولد الاستجابة التفاعلية للإجهاد العصبي. درسنا الآثار المباشرة لسلوكيات الرعاية علي ميثيل الحمض النووي في الرضع وكذلك الاستجابة التفاعلية للرضع. وتم تقييم الرضع والأمهات (العدد = 128) اثناء اللعب الحر عندما كان عمر الرضع 5 أشهر. وتم ترميز الاستجابة الاموميه واللمس المناسب وعينت الخلايا الظهاريه للرضع لتقييم ميثيل الحمض النووي من الجينات مستقبلات جلوكورتيكويد ، NR3c1 اكسون 1F. وتم تقييم تفاعل الكورتيزول للرضع استجابه لنموذج الوجه الثابت. وكانت المستويات الأكبر من الاستجابة الاموميه واللمس المناسب مرتبطة بمستوى أقل من ميثيل الحمض النووي في مناطق محدده في NR3c1 اكسون 1F ، ولكن فقط للإناث. ولم يكن هناك ارتباط مع استجابه الام واللمس المناسب أو ميثيل الحمض النووي من NR3c1 اكسون 1Fعلي الكورتيزول قبل الإجهاد أو الاستجابة التفاعلية للكورتيزول. وتناقش نتائجنا فيما يتعلق بنماذج البرمجة التي تضع رعاية الامومه كعامل مهم في برمجه استجابة الرضع التفاعلية للإجهاد العصبي.

The World Health Organization recently reported that maternal mental health is a major public health concern. As many as one in four women suffer from psychiatric disorders at some point during pregnancy or the first postpartum year. Furthermore, self-injurious thoughts and behaviors (SITBs) represent one of the leading causes of death among women during this time. Thus, efforts to identify women at risk for serious forms of psychopathology and especially for SITBs are of utmost importance. Despite this urgency, current single-diagnostic approaches fail to recognize a significant subset of women who are vulnerable to perinatal stress and distress. The current study was among the first to investigate emotion dysregulation—a multilevel, transdiagnostic risk factor for psychopathology—and its associations with stress, distress, and SITBs in a sample of pregnant women (26–40 weeks gestation) recruited to reflect a range of emotion dysregulation. Both self-reported emotion dysregulation and respiratory sinus arrhythmia, a biomarker of emotion dysregulation, demonstrated expected associations with measures of mental health, including depression, anxiety, borderline personality pathology, and SITBs. In addition, self-reported emotion dysregulation was associated with blunted respiratory sinus arrhythmia responsivity to an ecologically valid infant cry task. Findings add to the literature considering transdiagnostic risk during pregnancy using a multiple-levels-of-analysis approach.

It is now well established that early experiences of adversity play a central role in development of many mental health problems in adulthood. However, the effects are more pronounced and detrimental for some individuals compared to others. Informed by the biological sensitivity to context model, an evolutionary-developmental model of individual differences in stress responsivity, the present chapter highlights the role of stress response system as one moderating mechanism in the pathway between early life experiences and development of internalizing and externalizing behaviors. The model posits that the magnitude and integrated patterns of autonomic and adrenocortical responses to psychosocial challenges are indicators of the organisms’ level of susceptibility to both positive and negative environmental influences. The final part of the chapter focuses on the role of early life experiences in programming the functioning of stress response systems, development of adaptive stress responsivity patterns, and related behavioral profiles.

Emotion dysregulation is a pervasive clinical problem that likely emerges from complex Gene × Environment interactions across development. Epigenetic processes provide a molecular basis by which genotype interacts with the environment across the lifespan to produce phenotype. Epigenetics is defined by molecular processes occurring on and around the genome that regulate gene activity without changing DNA sequence. This chapter describes how epigenetic mechanisms are assessed and provides a brief review of current research on epigenetics, emotion dysregulation, and associated disorders. It then highlights four biological pathways of interest, the serotonin, dopamine, and norepinephrine systems and the limbic-hypothalamic pituitary adrenal (L-HPA) axis, and argues that, to advance understanding of the pathophysiology of emotion dysregulation, biological pathways rather than single genes must be measured. The chapter describes challenges for the field of epigenetics and how novel methods could be leveraged to overcome those challenges.

During pregnancy, a woman's emotions can have longstanding implications for both her own and her child's health. Within-person emotional concordance refers to the simultaneous measurement of emotional responses across multiple levels of analysis. This method may provide insight into how pregnant women experience emotions in response to stress. We enrolled 162 pregnant women and assessed concordance through autonomic physiology (electrodermal activity [EDA], respiratory sinus arrhythmia [RSA]), and coded behavior (Prosocial, Flight, Displacement) during the Trier Social Stress Test-Speech. We used multilevel models to examine behavioral-physiological concordance and whether self-reported emotion dysregulation moderated these effects. Participants exhibited EDA-Prosocial concordance, suggesting that prosocial behavior may be a marker of stress. Emotion dysregulation did not moderate concordance. These findings provide novel information about behavioral coping to stress in pregnancy. Given the importance of observed behavior in the maintenance and treatment of psychopathology, these findings may provide a launchpad for future perinatal intervention research.

OBJECTIVES: We sought to determine if variations in maternal care alter DNA methylation in term, healthy, 5-month-old infants. This work was based on landmark studies in animal models demonstrating that nurturing care by dams would alter their newborns’ stress responses through epigenetic mechanisms. We used breastfeeding as a proxy for animal maternal behavior. We hypothesized alterations in DNA methylation of the glucocorticoid receptor gene and less hypothalamic stress response in infants of mothers who breastfed their infants versus infants of mothers who did not breastfeed. METHODS: A cohort study of term, healthy infants and their mothers who did (n = 21) or did not (n = 21) breastfeed for the first 5 months was used in this analysis. Cortisol stress reactivity was measured in infant saliva by using a mother-infant interaction procedure and DNA methylation of an important regulatory region of the glucocorticoid receptor gene. Changes in DNA methylation of this gene in humans were compared to homologous regions of the rat gene. DNA samples were prepared from cheek swabs and subjected to quantitative analysis of the extent of methylation by using sensitive sequencing techniques. RESULTS: Breastfeeding was associated with decreased DNA methylation of the glucocorticoid receptor promoter and decreased cortisol reactivity in 5-month-old infants. Decreased DNA methylation occurred in the promoter region involved in regulation of the hypothalamic-pituitary-adrenal and immune system responses. CONCLUSIONS: Maternal care in humans may impact the hypothalamic-pituitary-adrenal stress response through behavioral programming and manifest as offspring epigenetic change. These results explain, in part, some of the positive effects observed in children who are breastfed.

Deficits in social engagement emerge in autism during the infant and toddler period and may be related to emotion regulation and stress response systems. This study examined patterns of growth in autonomic functioning related to autism diagnosis and addresses the hypothesis that there are differences in autonomic functioning related to autism in infancy. Heart rate (HR) and respiratory sinus arrhythmia (RSA) were measured at 8 time points from 1 to 72 months of age in infants later diagnosed with autism (n = 12) and a non-autistic comparison group (n = 106). Multilevel models were used to describe the developmental course of HR and RSA and to test the effect of autism diagnosis on growth trajectories. Both groups showed an expected age-related decrease in HR and increase in RSA. Groups did not differ in the rate of decrease of HR over time. However, infants with autism demonstrated a smaller linear increase in RSA, indicating slower growth in RSA over time in comparison to controls. These results suggest that differences in physiological regulation may develop with age in autism. The slowed RSA growth in autism was most evident after 18 months of age, at a time when behavioral symptoms become prominent. This is consistent with the view that RSA is a marker of functional status in autism rather than a cause of social deficits in autism.

The purpose of the current study was to predict concurrent levels of problem behaviors from young children's baseline cortisol and attachment classification, a proxy for the quality of caregiving experienced. In a sample of 58 children living at or below the federal poverty threshold, children's baseline cortisol levels, attachment classification, and problem behaviors were assessed at 17 months of age. We hypothesized that an interaction between baseline cortisol and attachment classification would predict problem behaviors above and beyond any main effects of baseline cortisol and attachment. However, based on limited prior research, we did not predict whether or not this interaction would be more consistent with diathesis-stress or differential susceptibility models. Consistent with diathesis-stress theory, the results indicated no significant differences in problem behavior levels among children with high baseline cortisol. In contrast, children with low baseline cortisol had the highest level of problem behaviors in the context of a disorganized attachment relationship. However, in the context of a secure attachment relationship, children with low baseline cortisol looked no different, with respect to problem behavior levels, then children with high cortisol levels. These findings have substantive implications for the socioemotional development of children reared in poverty.

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. The sample included 860 children aged 16 years participating in the Maternal Lifestyle Study, a multisite longitudinal study of children with prenatal exposure to cocaine and other substances. Structural equation modeling was used to test pathways between prenatal substance exposure, early adversity, baseline RSA, baseline cortisol, neurobehavioral disinhibition, drug use, and sexual behavior outcomes. Concordance was studied by examining separate male and female models in which there were statistically significant interactions between baseline RSA and cortisol. Prenatal substance exposure was operationalized as the number of substances to which the child was exposed. An adversity score was computed based on caregiver postnatal substance use, depression and psychological distress, number of caregiver changes, socioeconomic and poverty status, quality of the home environment, and child history of protective service involvement, abuse and neglect. RSA and cortisol were measured during a baseline period prior to the beginning of a task. Neurobehavioral disinhibition, based on composite scores of behavioral dysregulation and executive dysfunction, substance use and sexual behavior were derived from questionnaires and cognitive tests administered to the child. Findings were sex specific. In females, those with discordance between RSA and cortisol (high RSA and low cortisol or low RSA and high cortisol) had the most executive dysfunction which, in turn, predicted earlier initiation of alcohol by age 16. Among boys, there also existed a significant baseline RSA by baseline cortisol interaction. Boys with low baseline RSA and high baseline cortisol had the highest levels of behavioral dysregulation. This increase in behavioral dysregulation was in turn related to initiation of alcohol use by age 16 and lower age of first sexual intercourse. We found sex-specific pathways to the initiation of alcohol use and risky sexual behavior through the combined activity of parasympathetic and neuroendocrine functioning. The study of multiple physiological systems may suggest new pathways to the study of age of onset of substance use and engagement in risky sexual behavior in adolescents.