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Perinatal Developmental Origins of Self-Regulation
Abstract
The developmental origins of behavior, health, and disease (DOBHaD) hypothesis examines the short- and long-term effects of environmental conditions early in life on phenotypic variations in behavior, health, and disease. The prenatal and early postnatal periods are times of great opportunity and considerable risk, and their influence can extend over a lifetime. We review human studies on the association of maternal anxiety, depression, and stress during pregnancy with offspring self-regulation from infancy onwards. In the large majority of the studies, this association generally persisted after controlling for postnatal maternal mood and other relevant confounders in the pre- and postnatal periods. Several gestational ages were reported to be vulnerable to the long-term effects of exposure to maternal anxiety, depression, and stress during pregnancy and different mechanisms are likely to operate at different stages. Possible underlying mechanisms (e.g., epigenetic dysregulation) are just starting to be explored. We also discuss postnatal factors (e.g., child–parent attachment) that may modulate the effects of maternal anxiety, depression, and/or stress during pregnancy on offspring self-regulation. Long-term observational studies should identify molecular, neurophysiological, neuropsychological, and postnatal psychosocial factors involved in the association of maternal anxiety, depression, and stress during pregnancy with offspring self-regulation and may lead to the development of innovative prevention and intervention studies addressing maternal anxiety, depression, and/or stress during pregnancy and its potential consequences. Long-term intervention studies are needed for evaluating the efficacy of stress reduction programs to reduce maternal anxiety, depression, and stress during pregnancy and adverse somatic and mental health outcomes in the offspring.
... The second potential mechanism could be that prenatal opioid exposure alters the development of dopaminergic reward-related circuits, which may in turn lead to dysregulated, hyperactive behavior (Sithisarn et al., 2017). What's more, DOHaD studies have documented a strong relationship between maternal depression and stress during pregnancy and children's subsequent behavior regulation trajectories, even after controlling for confounders such as postnatal maternal depression (Henrichs & Van den Bergh, 2015). They also suggest that this relationship may be continuously modulated by environmental experiences (Henrichs & Van den Bergh, 2015). ...
... What's more, DOHaD studies have documented a strong relationship between maternal depression and stress during pregnancy and children's subsequent behavior regulation trajectories, even after controlling for confounders such as postnatal maternal depression (Henrichs & Van den Bergh, 2015). They also suggest that this relationship may be continuously modulated by environmental experiences (Henrichs & Van den Bergh, 2015). Our novel findings of the independent, additive contributions of prenatal risk, social risk, postnatal caregiving quality, and caregiver changes to predicting children's emotional and behavioral problem trajectories add important information about the potential mechanisms placing infants born to opioid dependent mothers at increased psychopathological risk. ...
Maternal opioid use in pregnancy has increased dramatically. Knowledge about children’s longer-term emotional and behavioral development after prenatal opioid exposure is scarce. A regional sample of 89 opioid-exposed and 104 non-exposed comparison children were studied prospectively at ages 2, 4.5, and 9 years using the Strengths and Difficulties Questionnaire (SDQ) completed by primary caregivers. Across all childhood assessments, opioid-exposed children obtained significantly higher total difficulties scores than non-exposed comparison children. Growth curve modeling revealed that, relative to their same age peers, opioid-exposed children’s emotional and behavioral difficulties significantly worsened over time. Moreover, fixed effects estimates showed that total difficulties trajectories were poorer for children subject to higher prenatal risk (Est = 1.78, 95% CI = [0.46, 3.09]) who were born to mothers with high levels of social adversity (1.11 [0.51, 1.71]), and were then raised in families characterized by high levels of psychosocial risk (1.94 [0.90, 2.98]) and unstable caregiving (1.91 [0.33, 3.48]). A complex set of pre- and postnatal processes contribute to opioid-exposed children’s emotional and behavioral development. Efforts to mitigate the long-term consequences of opioid use in pregnancy need to consider both children’s and their caregivers’ biopsychosocial risks.
... Consistent with previous work, our findings indicate that early adversity-including both preterm birth and institutional deprivation-is associated with poorer effortful control abilities (Anderson & Doyle, 2004;Gunnar & Van Dulmen, 2007;Jaekel, Eryigit-Madzwamuse, & Wolke, 2016). These findings suggest that effortful control abilities are more vulnerable to a sensitive period of development in the earliest months of life than are other dimensions of temperament (Henrichs & Van den Bergh, 2015). Given that children and adolescents' selfcontrol has also been shown to be malleable (Diamond & Lee, 2011;Piquero, Jennings, & Farrington, 2010) and that even small increases in childhood self-control confer long-term benefits (Moffitt et al., 2011), understanding its role in developmental cascades leading from early adversity to adulthood outcomes could shed light on optimal windows for intervention for preterm and postinstitutionalized children. ...
Both preterm birth and early institutional deprivation are associated with neurodevelopmental impairment – with both shared and distinctive features. To explore shared underlying mechanisms, this study directly compared effects of these putative risk factors on temperament profiles in six-year-olds: Children born very preterm (<32 weeks gestation) or at very low birthweight (<1500g) from the Bavarian Longitudinal Study (n=299); and children who experienced > 6 months of deprivation in Romanian institutions from the English and Romanian Adoptees Study (n=101). The former were compared with 311 healthy term born controls and the latter with 52 non-deprived adoptees. At 6 years, temperament was assessed via parent reports across 5 dimensions: effortful control, activity, shyness, emotionality, and sociability. Very preterm/very low birthweight and post-institutionalized children showed similarly aberrant profiles in terms of lower effortful control (preterm = -0.50 [95% CI= -0.67 to -0.33]; post-institutionalized = -0.48 [-0.82 to -0.14]) compared to their respective controls. Additionally, post-institutionalized children showed higher activity, whereas very preterm/very low birthweight children showed lower shyness. Preterm birth and early institutionalization are similarly associated with poorer effortful control, which might contribute to long-term vulnerability. More research is needed to examine temperamental processes as common mediators of negative long-term outcomes following early adversity. </p
... The relationship between mother and infant may be altered by maternal anxiety, resulting in lack of engagement, and interaction with the infant (24). The impact of the lack of engagement between mother and infant may result in neurological and emotional development alterations in the infant and affect their ability to adapt, regulate, and moderate behavior (25)(26)(27)(28)(29)(30). Additional studies have reported an association between the physiological effects of anxiety in pregnancy and child neurodevelopment, including developmental delays (31,32), negative childhood emotionality (33), variances in attention deficit hyperactivity disorder, and anxious symptoms at various ages during childhood (34)(35)(36). ...
Background: Most research efforts toward prenatal maternal anxiety has been situated in high-income countries. In contrast, research from low- and middle-income countries has focused on maternal depression and prenatal maternal anxiety in low- and middle-income countries remains poorly understood.
Objectives: To examine whether dimensions and attributes of current maternal anxiety assessment tools appropriately capture South Asia women's experiences of perinatal distress during pregnancy.
Design: We conducted a rapid review with best fit framework synthesis, as we wished to map study findings to an a priori framework of dimensions measured by prenatal maternal anxiety tools.
Data Sources: We searched MEDLINE, PsycINFO, and CINAHL and gray literature in November 2016. Studies were included if published in English, used any study design, and focused on women's experiences of prenatal/antenatal anxiety in South Asia.
Review Methods: Study quality was assessed using the Effective Public Health Practice Project Quality Assessment Tool and Critical Appraisal Skills Programme Qualitative Checklist. Study findings were extracted to an a priori framework derived from pregnancy-related anxiety tools.
Results: From 4,177 citations, 9 studies with 19,251 women were included. Study findings mapped to the a priori framework apart from body image. A new theme, gender inequality, emerged from the studies and was overtly examined through gender disparity, gender preference of fetus, or domestic violence.
Conclusions: Gender inequality and societal acceptability of domestic violence in South Asian women contextualizes the experience of prenatal maternal anxiety. Pregnancy-related anxiety tools should include domains related to gender inequality to better understand their influence on pregnancy outcomes.
... Self-control is harder to influence during adulthood but evidence from the psychology literature shows that this trait has higher malleability at young ages (Henrichs and Van den Bergh, 2015). However, despite the potential to have an impact on this behavioral trait when targeting children, only Jamison, Karlan, and Zinman (2014) has measured the effect of financial education on this construct. ...
Using data from a randomized controlled trial in 300 public high schools in Peru, this paper studies the potential of school-based financial education programs for youth. The intervention improves students' and teachers' financial knowledge by 0.14 SD and 0.32 SD, respectively. The impact of the intervention also extends to socioemotional traits and behavior, as sizable positive impacts on self-control and consumption habits among students are identified. Teachers in the treatment group become more impulsive and risk averse, and they are more likely to save (9 percentage points) and to save formally (14 percentage points).
Relying on a large-scale experiment in Peru, this study evaluates the effects of an in-class intervention on financial literacy and financial behavior. As soon as the program is over, treated students record significant financial literacy gains that do not hinder their academic performance. The program also leads to immediate changes in downstream financial behavior as measured by financial autonomy and financial savviness. Credit bureau records gathered three years later show that early improvements in financial literacy translate into limited, but positive long-lasting changes in financial behavior. The treatment did not affect students’ credit or repayment behavior on the extensive margin, but, among those few with outstanding loans, it reduced arrears by 20%.
A potential pathway underlying the association between prenatal exposure to maternal psychological problems and childhood externalizing problems is child self-regulation. This prospective study ( N = 687) examined whether self-regulated compliance mediates the relation between maternal affective problems and hostility during pregnancy and childhood externalizing problems, and explored moderation by child polygenic risk scores for aggression and sex. Self-regulated compliance at age 3 was observed in mother–child interactions, and externalizing problems at age 6 were reported by mothers and teachers. Polygenic risk scores were calculated based on a genome-wide association study of aggressive behavior. Self-regulated compliance mediated the associations between maternal psychological problems and externalizing problems. Aggression PRS was associated with higher externalizing problems reported by mothers. No evidence was found of moderation by aggression PRS or sex. These findings support the hypothesis that maternal psychological problems during pregnancy might influence externalizing problems through early self-regulation, regardless of child genetic susceptibility or sex.
This paper evaluates if the excitement about school-based financial education is warranted. First, relying on recent experimental evidence, the paper takes stock of the impact of financial education programs aimed at reaching children and youth. Second, it complements existing studies by focusing on the potentially negative unintended effects of these programs. Relying on data from a large-scale randomized controlled trial (RCT) in Peru, this paper investigates whether financial education programs have spillover effects on academic outcomes or if they widen initial inequalities due to heterogeneous treatment impacts. While delivery models that incorporate a mandatory course requirement yield large and robust impacts on financial literacy, voluntary after-school programs yield meager effects. These gains do not come at the cost of pervasive effects on the probability to pass a grade. Moreover, the impact of school-based financial education seems to be very inclusive, as treatment effects tend to be uniform across different sub-samples.
In this chapter, we present our recently conceptualized model on Developmental Origins of Behavior, Health, and Disease (DOBHaD) in which we incorporate the results of four of our studies as examples to demonstrate how each topic influenced the model; in addition, we provide a brief overview of relevant literature. The study of DOBHaD encompasses both, short-and long-term consequences of conditions in the environment relevant to behavior, health, and disease risk and addresses research issues related to the interface between developmental, behavioral, and medical science. In the first section, one early and one later study from the Leuven prospective follow-up project are described. Study 1 examines the influence of maternal emotions on fetal and neonatal behavioral staterelated activity and on infant activity. Study 2 examines the relationship between fetal behavioral states and self-regulation in childhood and adolescence. In the second section, two recent studies from the Tilburg prospective follow-up project are described. Study 3 explores how variation in both negative emotions (i.e., maternal anxiety) and positive emotions (i.e., maternal mindfulness) influence infant neurocognitive development. Study 4 explores the issue of how exposure to a past, resolved maternal anxiety disorder influences maternal heart rate variability during pregnancy as well as infant heart rate variability, which in turn influences infant temperament. In the final section we summarize our results, use them to explain applications of the DOBHaD model, and speculate on potential clinical implications.
The classic diathesis–stress framework, which views some individuals as particularly vulnerable to adversity, informs virtually all psychiatric research on behavior–gene–environment (G × E) interaction. An alternative framework of ‘differential susceptibility’ is proposed, one which regards those most susceptible to adversity because of their genetic make up as simultaneously most likely to benefit from supportive or enriching experiences—or even just the absence of adversity. Recent G × E findings consistent with this perspective and involving monoamine oxidase-A, 5-HTTLPR (5-hydroxytryptamine-linked polymorphic region polymorphism) and dopamine receptor D4 (DRD4) are reviewed for illustrative purposes. Results considered suggest that putative ‘vulnerability genes’ or ‘risk alleles’ might, at times, be more appropriately conceptualized as ‘plasticity genes’, because they seem to make individuals more susceptible to environmental influences—for better and for worse.
Background: Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries.
Methods: We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions.
Findings: Global life expectancy for both sexes increased from 65·3 years (UI 65·0–65·6) in 1990, to 71·5 years (UI 71·0–71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8–48·2) to 54·9 million (UI 53·6–56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25–39 years and older than 75 years and for men aged 20–49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions.
Interpretation: For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
Orienting to salient events in the environment is a first step in the development of attention in young infants. Electrophysiological studies have indicated that in newborns and young infants, sounds with widely distributed spectral energy, such as noise and various environmental sounds, as well as sounds widely deviating from their context elicit an event-related potential (ERP) similar to the adult P3a response. We discuss how the maturation of event-related potentials parallels the process of the development of passive auditory attention during the first year of life. Behavioral studies have indicated that the neonatal orientation to high-energy stimuli gradually changes to attending to genuine novelty and other significant events by approximately 9 months of age. In accordance with these changes, in newborns, the ERP response to large acoustic deviance is dramatically larger than that to small and moderate deviations. This ERP difference, however, rapidly decreases within first months of life and the differentiation of the ERP response to genuine novelty from that to spectrally rich but repeatedly presented sounds commences during the same period. The relative decrease of the response amplitudes elicited by high-energy stimuli may reflect development of an inhibitory brain network suppressing the processing of uninformative stimuli. Based on data obtained from healthy full-term and pre-term infants as well as from infants at risk for various developmental problems, we suggest that the electrophysiological indices of the processing of acoustic and contextual deviance may be indicative of the functioning of auditory attention, a crucial prerequisite of learning and language development.
Maternal antenatal anxiety is associated with an increased risk of behavioral disturbances in offspring. Recent work has suggested that the effect of maternal antenatal anxiety on infant temperament at 6 months is moderated by the serotonin transporter polymorphism 5-HTTLPR, with carriers of the short allele more susceptible to the adverse behavioral outcomes of maternal antenatal anxiety. These findings, however, are yet to be replicated and extended beyond infancy. The aim of the current study was to assess this same potential moderator (5-HTTLPR) in a large population-based cohort study, and to determine whether or not the effects persist into childhood and early adolescence.
Data from the Avon Longitudinal Study of Children and Parents (ALSPAC) cohort (N = 3,946) were used to assess whether the 5-HTTLPR genotype moderated the association between self-reported maternal antenatal anxiety (Crown Crisp Index) in pregnancy, and child temperament at 6 months (Infant Temperament Questionnaire), and also later behavioral and emotional problems on the Strengths and Difficulties Questionnaire from age 4 to 13 years.
We found no evidence to suggest that the 5-HTTLPR polymorphism moderated the effects of maternal antenatal anxiety on infant temperament at 6 months or infant behavioral and emotional problems from childhood through to adolescence.
Our results, based on a large prospective community sample that assessed children from infancy to early adolescence, provide a thorough test of, but no evidence for, a genetic moderation of the effects of maternal antenatal anxiety by 5-HTTLPR.
Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats.
As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed
reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid
receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing
hormone messenger RNA. Each measure was significantly correlated with the frequency of maternal licking and grooming (all
r's > −0.6). These findings suggest that maternal behavior serves to “program” hypothalamic-pituitary-adrenal responses to
stress in the offspring.
Background:
Maternal depression and anxiety during pregnancy have been associated with offspring-attention deficit problems.
Aim:
We explored possible intrauterine effects by comparing maternal and paternal symptoms during pregnancy, by investigating cross-cohort consistency, and by investigating whether parental symptoms in early childhood may explain any observed intrauterine effect.
Methods:
This study was conducted in two cohorts (Generation R, n = 2,280 and ALSPAC, n = 3,442). Pregnant women and their partners completed questionnaires to assess symptoms of depression and anxiety. Child attention problems were measured in Generation R at age 3 with the Child Behavior Checklist, and in ALSPAC at age 4 with the Strengths and Difficulties Questionnaire.
Results:
In both cohorts, antenatal maternal symptoms of depression (Generation R: OR 1.23, 95% CI 1.05-1.43; ALSPAC: OR 1.33, 95% CI 1.19-1.48) and anxiety (Generation R: OR 1.24, 95% CI 1.06-1.46; ALSPAC: OR 1.32, 95% CI 1.19-1.47) were associated with a higher risk of child attention problems. In ALSPAC, paternal depression was also associated with a higher risk of child attention problems (OR 1.11, 95% CI 1.00-1.24). After adjusting for maternal symptoms after giving birth, antenatal maternal depression and anxiety were no longer associated with child attention problems in Generation R. Moreover, there was little statistical evidence that antenatal maternal and paternal depression and anxiety had a substantially different effect on attention problems of the child.
Conclusions:
The apparent intrauterine effect of maternal depression and anxiety on offspring-behavioural problems may be partly explained by residual confounding. There was little evidence of a difference between the strength of associations of maternal and paternal symptoms during pregnancy with offspring-attention problems. That maternal symptoms after childbirth were also associated with offspring-behavioural problems may indicate a contribution of genetic influences to the association.
This prospective, longitudinal study aimed to investigate relationships between indicators of maternal prenatal stress, infant birth outcomes and early temperament. We examined the pattern of associations and postulated pathways between physiological (cortisol plasma concentrations) and self-report indices (stress, anxiety) of maternal prenatal stress, cortisol in the amniotic fluid, birth outcomes and infant temperament at 3 months. The sample consisted of 158 women undergoing amniocentesis in the 2nd trimester of pregnancy. Questionnaire measures of maternal stress and anxiety were found to be unrelated to cortisol in plasma or amniotic fluid. Maternal cortisol was related to amniotic cortisol, which in turn was associated with lower birth weight. Birth weight predicted infant fear and distress to limitation at 3 months old. We found trend-like indirect effects of amniotic fluid on infant distress to limitation and fear via birth weight. This is one of the few studies to simultaneously assess the role of maternal and amniotic fluid cortisol on birth outcomes and infant emotional development. The results suggest that foetal cortisol may be an important predictor of infant outcomes and shed light on the mechanisms through which prenatal maternal stress affects infant psychological health.
The prefrontal cortex (PFC) receives input from all other cortical regions and functions to plan and direct motor, cognitive, affective, and social behavior across time. It has a prolonged development, which allows the acquisition of complex cognitive abilities through experience but makes it susceptible to factors that can lead to abnormal functioning, which is often manifested in neuropsychiatric disorders. When the PFC is exposed to different environmental events during development, such as sensory stimuli, stress, drugs, hormones, and social experiences (including both parental and peer interactions), the developing PFC may develop in different ways. The goal of the current review is to illustrate how the circuitry of the developing PFC can be sculpted by a wide range of pre- and postnatal factors. We begin with an overview of prefrontal functioning and development, and we conclude with a consideration of how early experiences influence prefrontal development and behavior.
One might expect that children with varying genetic mutations or children raised in low socioeconomic status environments would display different deficits. Although this expectation may hold for phenotypic outcomes in older children and adults, cross-syndrome comparisons in infancy reveal many common neural and sociocognitive deficits. The challenge is to track dynamic trajectories over developmental time rather than focus on end states like in adult neuropsychological studies. We contrast the developmental and adult approaches with examples from the cognitive and social domains, and we conclude that static models of adult brain lesions cannot be used to account for the dynamics of change in genetic and environmentally induced disorders in children.
Background:
Accumulating data from animal and human studies indicate that the prenatal environment plays a significant role in shaping children's neurocognitive development. Clinical, epidemiologic, and basic science research suggests that two experiences relatively common in pregnancy - an unhealthy maternal diet and psychosocial distress - significantly affect children's future neurodevelopment. These prenatal experiences exert their influence in the context of one another and yet, almost uniformly, are studied independently.
Scope and method of review:
In this review, we suggest that studying neurocognitive development in children in relation to both prenatal exposures is ecologically most relevant, and methodologically most sound. To support this approach, we selectively review two research topics that demonstrate the need for dual exposure studies, including exemplar findings on (a) the associations between pregnant women's inadequate maternal intake of key nutrients - protein, fat, iron, zinc, and choline - as well as distress in relation to overlapping effects on children's neurocognitive development; and (b) cross-talk between the biology of stress and nutrition that can amplify each experience for the mother and fetus,. We also consider obstacles to this kind of study design, such as questions of statistical methods for 'disentangling' the exposure effects, and aim to provide some answers.
Conclusion:
Studies that specifically include both exposures in their design can begin to determine the relative and/or synergistic impact of these prenatal experiences on developmental trajectories - and thereby contribute most fully to the understanding of the early origins of health and disease.
Prenatal exposure to maternal stress can have lifelong implications for psychological function, such as behavioral problems and even the development of mental illness. Previous research suggests that this is due to transgenerational epigenetic programming of genes operating in the hypothalamic-pituitary-adrenal axis, such as the glucocorticoid receptor (GR). However, it is not known whether intrauterine exposure to maternal stress affects the epigenetic state of these genes beyond infancy. Here, we analyze the methylation status of the GR gene in mothers and their children, at 10-19 years after birth. We combine these data with a retrospective evaluation of maternal exposure to intimate partner violence (IPV). Methylation of the mother's GR gene was not affected by IPV. For the first time, we show that methylation status of the GR gene of adolescent children is influenced by their mother's experience of IPV during pregnancy. As these sustained epigenetic modifications are established in utero, we consider this to be a plausible mechanism by which prenatal stress may program adult psychosocial function.
The aim of this study was to investigate whether maternal anxiety that is temporary or chronic during the pre- and postnatal period predicts infant temperament. Mothers of 2997 infants in a population-based birth cohort reported levels of pregnancy-specific anxiety (Pregnancy Outcome Questionnaire) and general anxiety symptoms (Brief Symptom Inventory) prenatal and at 6 months postnatal. Temperament characteristics were assessed by maternal report using the Infant Behavior Questionnaire—Revised when the infants were 6 months of age. Maternal pregnancy-specific and general anxiety during the pre- and postnatal period were all independently associated with perceived infant temperamental difficulties. Chronically high maternal anxiety predicted the highest perceived infant activity level and negative affectivity. These findings show that different forms of maternal anxiety during both the pre- and postnatal period are independently related to perceived temperamental problems in infancy. They also emphasize the significance of chronic maternal anxiety for infant mental health. Copyright © 2009 John Wiley & Sons, Ltd.
Prenatal maternal psychopathology affects child development, but some children seem more vulnerable than others. Genetic variance in hypothalamic-pituitary-adrenal axis genes may influence the effect of prenatal maternal psychological symptoms on child emotional and behavioral problems. This hypothesis was tested in the Generation R Study, a population-based cohort from fetal life onward. In total, 1727 children of Northern European descent and their mothers participated in this study and were genotyped for variants in the glucocorticoid receptor (GR) gene (rs6189/rs6190, rs10052957, rs41423247, rs6195, and rs6198) and the FK506-binding protein 5 (FKBP5) gene (rs1360780). Prenatal maternal psychological symptoms were assessed at 20 weeks pregnancy and child behavior was assessed by both parents at 3 years. In a subsample of 331 children, data about cortisol reactivity were available. Based on power calculations, only those genetic variants with sufficient minor allele frequencies (rs41423247, rs10052957, and rs1360780) were included in the interaction analyses. We found that variation in GR at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child emotional and behavioral problems (beta 0.41, SE 0.16, p=0.009). This prenatal interaction effect was independent of mother's genotype and maternal postnatal psychopathology, and not found for prenatal psychological symptoms of the father. Moreover, the interaction between rs41423247 and prenatal psychological symptoms was also associated with decreased child cortisol reactivity (beta -2.30, p-value 0.05). These findings emphasize the potential effect of prenatal gene-environment interaction, and give insight in possible mechanisms accounting for children's individual vulnerability to develop emotional and behavioral problems.
Maternal exposure to stress during pregnancy is associated with significant alterations in offspring neurodevelopment and elevated maternal glucocorticoids likely play a central role in mediating these effects. Placental 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) buffers the impact of maternal glucocorticoid exposure by converting cortisol/corticosterone into inactive metabolites. However, previous studies indicate that maternal adversity during the prenatal period can lead to a down-regulation of this enzyme. In the current study, we examined the impact of prenatal stress (chronic restraint stress during gestational days 14-20) in Long Evans rats on HSD11B2 mRNA in the placenta and fetal brain (E20) and assessed the role of epigenetic mechanisms in these stress-induced effects. In the placenta, prenatal stress was associated with a significant decrease in HSD11B2 mRNA, increased mRNA levels of the DNA methyltransferase DNMT3a, and increased DNA methylation at specific CpG sites within the HSD11B2 gene promoter. Within the fetal hypothalamus, though we find no stress-induced effects on HSD11B2 mRNA levels, prenatal stress induced decreased CpG methylation within the HSD11B2 promoter and increased methylation at sites within exon 1. Within the fetal cortex, HSD11B2 mRNA and DNA methylation levels were not altered by prenatal stress, though we did find stress-induced elevations in DNMT1 mRNA in this brain region. Within individuals, we identified CpG sites within the HSD11B2 gene promoter and exon 1 at which DNA methylation levels were highly correlated between the placenta and fetal cortex. Overall, our findings implicate DNA methylation as a mechanism by which prenatal stress alters HSD11B2 gene expression. These findings highlight the tissue specificity of epigenetic effects, but also raise the intriguing possibility of using the epigenetic status of placenta to predict corresponding changes in the brain.
In this paper, we review evidence that supports the notion that intrinsic and extrinsic factors contribute to the development of self-control of emotions. Intrinsic factors include the infant's temperament, and cognitive processes such as attention and inhibitory control. Extrinsic factors involve the caregiving environment, sibling and peer relationships, and cultural expectations regarding emotional displays. Integrative approaches to the study of the development of self-control of emotion will be most fruitful if investigations examine the interplay, over time, among these internal and external factors.
Maternal postpartum emotional distress is quite common and can pose significant risk to mothers and infants. The current study investigated mothers' relationships with their partners during pregnancy and tested the hypotheses that perception of prenatal partner support is a significant predictor of changes in maternal emotional distress from midpregnancy to postpartum, and contributes to maternal ratings of infant distress to novelty. Using a prospective longitudinal design, 272 adult pregnant women were interviewed regarding their partner support, relationship satisfaction, and interpersonal security (attachment style and willingness to seek out support), and they completed standardized measures of prenatal symptoms of depression and anxiety (distress). At 6 to 8 weeks' postpartum, mothers reported these symptoms again and completed measures of their infants' temperament. Structural equation modeling (SEM) was used to test direct and indirect contributions of partner support, relationship satisfaction, and interpersonal security to maternal and infant postpartum distress. Mothers who perceived stronger social support from their partners midpregnancy had lower emotional distress postpartum after controlling for their distress in early pregnancy, and their infants were reported to be less distressed in response to novelty. Partner support mediated the effects of mothers' interpersonal security and relationship satisfaction on maternal and infant outcomes. A high-quality, supportive partner relationship during pregnancy may contribute to improved maternal and infant well-being postpartum, indicating a potential role for partner relationships in mental health interventions, with possible benefits for infants as well.
Prenatal maternal anxiety has detrimental effects on the offspring's neurocognitive development, including impaired attentional function. Antidepressants are commonly used during pregnancy, yet their impact on offspring attention and their interaction with maternal anxiety has not been assessed. The authors used P50 auditory sensory gating, a putative marker of early attentional processes measurable in young infants, to assess the impact of maternal anxiety and antidepressant use.
A total of 242 mother-infant dyads were classified relative to maternal history of anxiety and maternal prenatal antidepressant use. Infant P50 auditory sensory gating was recorded during active sleep at a mean age of 76 days (SD=38).
In the absence of prenatal antidepressant exposure, infants whose mothers had a history of anxiety diagnoses had diminished P50 sensory gating. Prenatal antidepressant exposure mitigated the effect of anxiety. The effect of maternal anxiety was limited to amplitude of response to the second stimulus, while antidepressant exposure had an impact on the amplitude of response to both the first and second stimulus.
Maternal anxiety disorders are associated with less inhibition during infant sensory gating, a performance deficit mitigated by prenatal antidepressant exposure. This effect may be important in considering the risks and benefits of antidepressant use during pregnancy. Cholinergic mechanisms are hypothesized for both anxiety and antidepressant effects, although the cholinergic receptors involved are likely different for anxiety and antidepressant effects.
Stress-related variation in the intrauterine milieu may impact brain development and emergent function, with long-term implications in terms of susceptibility for affective disorders. Studies in animals suggest limbic regions in the developing brain are particularly sensitive to exposure to the stress hormone cortisol. However, the nature, magnitude, and time course of these effects have not yet been adequately characterized in humans. A prospective, longitudinal study was conducted in 65 normal, healthy mother-child dyads to examine the association of maternal cortisol in early, mid-, and late gestation with subsequent measures at approximately 7 y age of child amygdala and hippocampus volume and affective problems. After accounting for the effects of potential confounding pre- and postnatal factors, higher maternal cortisol levels in earlier but not later gestation was associated with a larger right amygdala volume in girls (a 1 SD increase in cortisol was associated with a 6.4% increase in right amygdala volume), but not in boys. Moreover, higher maternal cortisol levels in early gestation was associated with more affective problems in girls, and this association was mediated, in part, by amygdala volume. No association between maternal cortisol in pregnancy and child hippocampus volume was observed in either sex. The current findings represent, to the best of our knowledge, the first report linking maternal stress hormone levels in human pregnancy with subsequent child amygdala volume and affect. The results underscore the importance of the intrauterine environment and suggest the origins of neuropsychiatric disorders may have their foundations early in life.
The development of mental abilities during infancy is impressive and measurable. The pediatrician measures growth in head size, which reflects the growth of the brain. The neuropathologist measures cerebral DNA to estimate cell number and possible damage from malnutrition or other causes (Winick, 1970). The psychologist measures behavioral change by means of careful observations of responses to specific tasks. In this chapter we shall review critically infant tests and their contribution to the understanding of mental growth in the first months of life.
The Blackwell Handbook of Early Childhood Development presents a comprehensive summary of research into child development from age two to seven. Comprises 30 contributions from both established scholars and emerging leaders in the field. The editors have a distinguished reputation in early childhood development. Covers biological development, cognitive development, language development, and social, emotional and regulatory development. Considers the applications of psychology to the care and education of young children, treating issues such as poverty, media, and the transition to school. A valuable resource for students, scholars and practitioners dealing with young children.
Van den Bergh, B. R. H., & Mennes, M. (2006).The association between a mother’s anxiety during pregnancy and self-regulation during adolescence, Kind en Adolescent, 27 (1), 31-43.
Summary: 86 mother-child pairs were studied in a prospective study from the 12th week of pregnancy onwards. At the age of 14-15, 64 of these children completed three computerized cognitive tasks. ancovas indicated that compared with boys of mothers who experienced low to medium levels of anxiety during pregnancy, boys of highly anxious pregnant women reacted more impulsively in an encoding task and slower and more variably in a continuous performance task. In an inhibition task in which auditive signals indicated the responses they had to inhibit, no group differences in performance were found. It is assumed that these adolescents experience specific self-regulation problems due to prenatal programming. The literature and clinical implications are discussed briefly.
Does Prenatal Exposure to Maternal Anxiety Influence Information Processing in Two-month-Olds Infants? An Auditory ERP Study
Background. Exposure to atypical events during specific intrauterine periods may induce reprogramming of fetal brain development and influence postnatal cognitive development. Our study aimed to assess the influence of prenatal exposure to maternal anxiety on information processing related to language.
Methods: Seventy women completed the State-Trait Anxiety Inventory between their 9th and 15th week of pregnancy. Two months after birth we recorded auditory event-related potentials (AERP) in their infants using an oddball paradigm with a standard tone and three types of deviants: inter-stimulus interval deviants, white noise, and novel sounds. Repeated measures mixed-mode ANOVAs were run on the mean AERP amplitudes with the structure ‘Anterior-Posterior’(frontal,central,parietal) x‘Laterality’ (left,medial,right) as within-subjects factors, state anxiety as a continuous predictor variable and ‘Stateof alertness’(awake versus asleep) as between-subjects factor. The influence of several covariates was controlled: smoking, alcohol intake, birth weight controlled for gestational age at birth, postnatal maternal anxiety.
Results: The standard and inter-stimulus interval deviant tones elicited morphologically different auditory event-related potentials in infants whose mother reported high anxiety as opposed to infants of mothers with lower levels of anxiety during pregnancy (p<.05). No similar effects were found for the white noise and novel sounds.
Conclusions: These findings indicate that infants from highly anxious mothers process sounds with low information contents differently from infants born to mothers with low and medium levels of anxiety during their pregnancy. This difference may underlie the poorer language acquisition observed in other studies in children prenatally exposed to high levels of maternal anxiety.
Effects of Maternal Anxiety during Pregnancy on Novelty Processing in
Two-Month-Old Infants. An ERP Study. Renée A. Otte1, Marijke A.K.A.
Braeken1, Bea R.H. Van den Bergh1, István Winkler2,3. 1Department of
Clinical and Developmental Psychology, Tilburg University, Netherlands;
2Deparment of Experimental Psychology, Hungarian Academy of Sciences,
Hungary; 3Institute of Psychology, University of Szeged, Hungary.
Research into the effects of prenatal maternal stress and anxiety found
evidence for alterations in fetal neurodevelopment. Thus, there is need for
precise neurophysiologic measures predicting cognitive development later
in life. These measures should also be sensitive to individual differences in
sensory-cognitive function induced by prenatal stress.
The present study tested in 2-month-old infants whether prenatal maternal
anxiety affected the auditory mismatch negativity (MMN) event-related
brain potential (ERP). MMN is a cortical response elicited by contextually
deviant or novel sound events, reflecting how well infants can model the
auditory environment and how strongly they react to novelty. Maternal state anxiety
was measured with the state-anxiety inventory (n=56) between the
8th and 14th week of pregnancy. Two months after birth, infants’ ERPs were
recorded during a passive auditory oddball paradigm delivering four types of
sounds of 200ms duration at a uniform 300ms pre-stimulus interval: frequent
standard complex tones (500Hz; p=70%), tones with 100ms pre-stimulus
(p=10%), white noise segments (p=10%), and various environmental sounds
(p=10%). Deviance/novelty-related responses were calculated by subtracting
responses elicited by the standard tones separately from those elicited by
each of the infrequent sounds.
Prenatal exposure to maternal anxiety is associated with sensory-cognitive development in two month olds.
Background:
Processes studied under the Developmental origins of Behavior, Health and Disease (DOBHaD)-concept encompass variations in both typical and atypical developmental and maturational patterns which are seen as adaptation to the environment resulting from gene-environment interaction. The present study tested in 2-month-old infants whether prenatal exposure to maternal anxiety affected event-related response (ERP) to rapidly presented sound sequences, possibly reflecting altered capacity for sensory processing .
Methods:
Maternal state-anxiety (N=71) was measured with the State Trait Anxiety Inventory (STAI; M = 33; SD = 9) at 8-15 weeks of pregnancy. Infants ERPs were measured during 4 auditory oddball sequences with sound of 200ms duration at a uniform 300ms pre-stimulus interval: frequent standard complex tones (500Hz; p=07), tones with 100ms pre-stimulus (‘ISI-deviant’, p=.01), white noise segments (‘noise deviant’, p=.01), and various environmental sounds (‘novel deviant’, p=0.01).
Results:
Four repeated measures ANCOVAs with state-anxiety scores as predictor variable, Electrode Position (F3,Fz,F4,C3,Cz,C4,P3,Pz,P4) as within-subjects factor, and state of alertness (awake; asleep) as between-subjects control factor revealed a main effect of state-anxiety on peak latency and amplitude (p < .05) for the standard sound.
Discussion:
Our preliminary results demonstrate shorter peak latencies and larger amplitudes in response to rapid-paced sound sequences in infants exposed to elevated 1st trimester state-anxiety, suggesting increased responsivity. Changes in information processing are likely to result in further problems such as poor emotional and stress regulation. We therefore plan to analyse the deviants as well as other measures (e.g. maternal and infant cortisol and temperament) to empirically verify DOBHaD hypotheses.
The impact of early physical and social environments on life-long phenotypes is well known. Moreover, we have documented evidence for gene-environment interactions where identical gene variants are associated with different phenotypes that are dependent on early life adversity. What are the mechanisms that embed these early life experiences in the genome? DNA methylation is an enzymatically-catalyzed modification of DNA that serves as a mechanism by which similar sequences acquire cell type identity during cellular differentiation and embryogenesis in the same individual. The hypothesis that will be discussed here proposes that the same mechanism confers environmental-exposure specific identity upon DNA providing a mechanism for embedding environmental experiences in the genome, thus affecting long-term phenotypes. Particularly important is the environment early in life including both the prenatal and postnatal social environments.
We investigated whether parental family stress during pregnancy is associated with cognitive functioning in early childhood in a population-based cohort (n=3139). Family stress was assessed using the Family Assessment Device at the 20th week of pregnancy and was reported by mothers and fathers. Mothers completed the MacArthur Communicative Development Inventory, measuring children's verbal cognitive functioning, when children were 18 months and they completed the Parent Report of Children's Abilities, measuring nonverbal cognitive functioning, when children were 2 years old. Maternal prenatal family stress was related to children's low word comprehension and poorer nonverbal cognitive development independent of paternal reports. In a subset of 639 children, maternal prenatal family stress was also associated with observational assessments of poor effortful control at age 37 months. Paternal prenatal family stress was only related to poorer nonverbal cognitive development, independent of the mother. When both parents had high levels of prenatal family stress, children displayed particularly poor nonverbal cognitive development. These findings emphasize the significance of parental prenatal family stress for child developmental outcomes.
The association was investigated between psychological distress reported during each trimester of pregnancy and maternal ratings of temperament when the children were 6 months and 5 years of age. Mothers in the greater Helsinki area who were to give birth during a 1-year period completed a brief questionnaire describing their psychological adjustment and medical symptoms at each prenatal visit to government health clinics. Mothers rated their children's temperament at ages 6 months and 5 years. Maternal psychological distress during pregnancy was only modestly associated with infant temperament. However, maternal distress during the first trimester was associated with ratings of negative emotionality at age 5 years, with a stronger correlation for males. Inhibition at age 5 was predicted by infant distress to novelty, particularly for males.
Adverse antenatal maternal environments during pregnancy influence fetal development that consequently increases a risk of mental health problems including psychiatric disorders in offspring. Therefore, behavioral and brain alterations caused by adverse prenatal environmental conditions are generally considered as deficits. In this article, we propose a novel hypothesis, along with summarizing a body of literatures supporting it, that fetal neurodevelopmental alterations, particularly synaptic network changes occurring in the prefrontal cortex, associated with adverse prenatal environmental conditions may be adaptation to cope with expected severe postnatal environments, and therefore, psychiatric disorders may be able to be understood as adaptive strategies against severe environmental conditions through evolution. It is hoped that the hypothesis presented in this article stimulate and open a new venue on research toward understanding of biological mechanisms and therapeutic treatments of psychiatric disorders.
In several recent reports, the Carey Infant Temperament Questionnaire has been criticized as a measure of infant temperament. Instead, the dimensions of temperament and the diagnostic categories (i.e., "easy" vs. "difficult" temperament) derived from maternal responses to the questionnaire items have been associated with maternal demographic and personality characteristics and with maternal child-rearing attitudes assessed before the birth of the infant. In this article, results of previous research are reconsidered in light of suggestions and criticisms offered by several temperament researchers. In two new studies the revision of the Infant Temperament Questionnaire (ITQ) was used to assess infant temperament, and personality and/or attitudinal data from the mother were obtained prenatally. Results were consistent across all studies. Prenatally assessed characteristics of the mother, especially anxiety, significantly distinguish mothers whose responses to the ITQ items result in diagnosis of temperamental difficulty for their infants from those whose infants are diagnosed as temperamentally easy during the first 8 months of life. The data suggest that both the original and revised Carey infant temperament scales fail discriminant validity tests and are therefore of only limited use in identifying temperamentally difficult infants. (67 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
24 women (mean age 24 yrs) who had received ultrasound examinations and psychological interviews during the 3rd trimester of pregnancy were subsequently divided into a group of 12 Ss who had reported pregnancy problems (marital difficulties and ambivalence about the child) and another group of 12 Ss who had not. Ss were then observed at 3–5 mo postpartum in interactions with their infants and were given the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Nowicki-Strickland Internal–External Control Scale for Adults, measures of mothers' and infants' temperament, and a maternal developmental expectations and childrearing attitudes scale. The mothers who had experienced pregnancy problems were more depressed, anxious, and externalizing postpartum and expressed more punitive childrearing attitudes. These depressed mothers and their infants showed less optimal interaction behaviors. Results suggest that postpartum depression can be predicted from a simple set of questions regarding the mother's negative feelings about her marriage and her expectant child during the prenatal period. (19 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Studied the effect of maternal emotions during the pregnancy in 30 of 70 nulliparous women (age 18–30 yrs) with varying levels of anxiety. Emotions were studied during each pregnancy trimester and in the 1st, 10th, and 28th wk after birth, using the State-Trait Anxiety Inventory. During pregnancy Ss were tested for a number of variables, including social support, coping abilities, personality, and pregnancy anxiety, in addition to the administration of the Maternal–Fetal Attachment Scale. After birth, Ss answered questionnaires on the birth experience and the behavior of the neonates. Maternal emotions had a small but significant effect on occurrence and duration of fetal motor activity. Fetuses of women with high anxiety tended to be more active than fetuses of women with low anxiety. The prenatal influence was reflected in neonatal behavior. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Extensive evidence that personal experiences and environmental exposures are embedded biologically (for better or for worse) and the cumulative knowledge of more than four decades of intervention research provide a promising opportunity to mobilize evolving scientific insights to catalyze a new era of more effective early childhood policy and practice. Drawing on emerging hypotheses about causal mechanisms that link early adversity with lifelong impairments in learning, behavior, and health, this paper proposes an enhanced theory of change to promote better outcomes for vulnerable, young children by strengthening caregiver and community capacities to reduce or mitigate the impacts of toxic stress, rather than simply providing developmental enrichment for the children and parenting education for their mothers.
Language acquisition reflects a complex interplay between biology and early experience. Psychotropic medication exposure has been shown to alter neural plasticity and shift sensitive periods in perceptual development. Notably, serotonin reuptake inhibitors (SRIs) are antidepressant agents increasingly prescribed to manage antenatal mood disorders, and depressed maternal mood per se during pregnancy impacts infant behavior, also raising concerns about long-term consequences following such developmental exposure. We studied whether infants' language development is altered by prenatal exposure to SRIs and whether such effects differ from exposure to maternal mood disturbances. Infants from non-SRI-treated mothers with little or no depression (control), depressed but non-SRI-treated (depressed-only), and depressed and treated with an SRI (SRI-exposed) were studied at 36 wk gestation (while still in utero) on a consonant and vowel discrimination task and at 6 and 10 mo of age on a nonnative speech and visual language discrimination task. Whereas the control infants responded as expected (success at 6 mo and failure at 10 mo) the SRI-exposed infants failed to discriminate the language differences at either age and the depressed-only infants succeeded at 10 mo instead of 6 mo. Fetuses at 36 wk gestation in the control condition performed as expected, with a response on vowel but not consonant discrimination, whereas the SRI-exposed fetuses showed accelerated perceptual development by discriminating both vowels and consonants. Thus, prenatal depressed maternal mood and SRI exposure were found to shift developmental milestones bidirectionally on infant speech perception tasks.
The effects of maternal antenatal and postnatal anxiety and depression on infant negative behavioral reactivity were examined in a sample of 22 mother-infant pairs. Maternal anxiety and depression were assessed by standardized measures during the third trimester of pregnancy and postpartum. Infant negative behavioral responses to novelty were assessed using a previously validated measure at 4 months of age. Maternal anxiety and depression during the prenatal, but not the postnatal period, were related to infant negative behavioral reactivity to novelty. These data illustrate that prenatal maternal psychological state can exert persisting influences on human infant behavior.
Maternal discipline is an important predictor of child committed compliance. Maternal stress can affect both parenting and child development. In a large population-based cohort study (N = 613) we examined whether maternal discipline mediated the association between maternal stress during pregnancy and child compliance, and whether COMT or DRD4 polymorphisms moderated the association between maternal discipline and child compliance. Family-related and general stress were measured through maternal self-report and genetic material was collected through cord blood sampling at birth. Mother-child dyads were observed at 36 months in disciplinary tasks in which the child was not allowed to touch attractive toys. Maternal discipline and child compliance were observed in two different tasks and independently coded. The association between family stress during pregnancy and child committed compliance was mediated by maternal positive discipline. Children with more COMT Met alleles seemed more susceptible to maternal positive discipline than children with more COMT Val alleles. © 2012 Wiley Periodicals, Inc. Dev Psychobiol.
People born at a low birth weight are at increased risk of chronic adult disease including coronary heart disease, type 2 diabetes, cognitive decline and depression. Recent human and animal research has suggested programming of physiological stress response as an important linking mechanism. We review evidence from human studies, focusing on biological markers as early life indicators and laboratory-induced stress response as an outcome.Several studies show that indicators such as birth weight or length of gestation are associated with alterations in blood pressure, autonomic nervous system and hypothalamic–pituitary–adrenal axis (HPAA) response. In most studies these associations vary according to sex: low birth weight seems to be associated with higher autonomic nervous system response more clearly in females and with higher peripheral vascular resistance and HPAA response in males.The published studies have established the validity of the concept of early life programming of stress response. We believe that important future directions include focusing on specific early life exposures as predictors and on stress response in everyday life as an outcome.
The association between maternal anxiety during pregnancy and child development was studied prospectively in a group of 105 healthy Caucasian women and their infants. Anxiety was measured with the State-Trait Anxiety Inventory at 32 weeks’ gestation. Infant development was measured at three weeks postpartum by means of the Neonatal Behavioral Assessment Scale, and at one and two years by means of the Bayley Scales of Infant Development. Findings of the present study showed that, even when controlled for a variety of confounding variables, high maternal anxiety levels during late pregnancy were associated with lower mental developmental scores at the age of 2 years. It is suggested that especially attention related processes may be affected, and should be studied in future research. If these findings are confirmed by future research, identification of highly anxious women during gestation may provide an important opportunity to start a support program in order to optimize later infant stimulation and caretaking.
The Developmental Origins of Health and Disease (DOHaD) hypothesis studies the short- and long-term consequences of the conditions of the developmental environment for phenotypic variations in health and disease. Central to this hypothesis is the idea of interdependence of developmental influences, genes, and environment. Developmental programming effects are mediated by alterations in fundamental life functions, and the most enduring effects seem to occur if the main regulatory instances of the organ - the (epi)genome and the brain - are affected. Some new insights in the role of chromatin, in cellular development and differentiation, and neural plasticity from the field of epigenetics are introduced, followed by a section on epigenetics and brain development. It is proposed to extend the DOHaD hypothesis into the 'Developmental Origins of Behaviour, Health, and Disease' (DOBHaD) concept. Pregnancy and the early postnatal period are times of both great opportunity and considerable risk, and their influence can extend over a lifetime. The DOBHaD hypothesis opens fundamental new perspectives on preventing diseases and disorders.