Roseriet Beijers

Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis

Abstract Accumulating evidence from preclinical and clinical studies indicates that maternal psychosocial stress and anxiety during pregnancy adversely affect child outcomes. However, knowledge on the possible mechanisms underlying these relations is limited. In the present paper, we review the most often proposed mechanism, namely that involving the HPA axis and cortisol, as well as other less well-studied but possibly relevant and complementary mechanisms. We present evidence for a role of the following mechanisms: compromised placental functioning, including the 11β-HSD2 enzyme, increased catecholamines, compromised maternal immune system and intestinal microbiota, and altered health behaviors including eating, sleep, and exercise. The roles of (epi)genetics, the postnatal environment and the fetus are also discussed. We conclude that maternal prenatal psychosocial stress is a complex phenomenon that affects maternal emotions, behavior and physiology in many ways, and may influence the physiology and functioning of the fetus through a network of different pathways. The review concludes with recommendations for future research that helps our understanding of the mechanisms by which maternal prenatal stress exerts its effect on the fetus.

Maternal Prenatal Anxiety and Stress Predict Infant Illnesses and Health Complaints

OBJECTIVES: Evidence from both animals and humans suggests that maternal prenatal anxiety and stress can have adverse consequences on the offsprings development. Animal models also show that prenatal stress has programming effects on the physical health of the offspring, such as immune functioning. In human studies, however, physical health outcomes are often restricted to birth complications; studies on the effects of acquiring illnesses are scarce. This study aimed to examine whether maternal prenatal anxiety and stress, measured both by self-report and by cortisol physiology, are related to more infant illnesses and antibiotic use during the first year of life. METHODS: Participants in the study were 174 mothers with normal pregnancies and term deliveries (71 firstborns; 91 boys). The mothers filled out third-trimester questionnaires on general and pregnancy-specific anxiety and stress and provided saliva samples for circadian cortisol. Information on infant illnesses and antibiotic use was obtained through monthly maternal interviews across the infants first year of life. RESULTS: Hierarchical multiple regressions showed that, even after controlling for many relevant confounders, prenatal anxiety and stress predicted a considerable amount of variance in infant illnesses and antibiotic use: 9.3% for respiratory, 10.7% for general, 8.9% for skin, and 7.6% for antibiotic use. Digestive illnesses were not related to prenatal anxiety and stress. CONCLUSIONS: Although replication is warranted, to our knowledge, this is the first evidence linking maternal prenatal anxiety and stress to infant illnesses and antibiotic use early in life.

Cortisol reactivity in young infants

In this systematic review on empirical studies of cortisol reactivity to acute stressors in infants, we specifically focus on the role of infant age in the early development of cortisol reactivity to stressors. Our findings indicate that many psychological stressors do not provoke a cortisol reaction, but in response to physical stressors, the infant HPA-axis mostly reacts with a moderate increase in post-stressor cortisol. Furthermore, for physical stressors only, cortisol reactivity effect sizes decrease with infant age, although relatively little is known for infants older than 6 months. These data provide more insight in the role of infant age in the development of cortisol reactivity in response to acute stressors. We discuss the role of caregivers in buffering the cortisol response to both psychological and physical stressors, and recommend extending the current knowledge on infant cortisol reactivity.

Maternal prenatal stress and cortisol reactivity to stressors in human infants

Early life factors can shape the development of hypothalamic pituitary adrenal (HPA) axis. Maternal prenatal stress might constitute such an early environmental factor. As little is known about the relation between maternal prenatal stress and cortisol reactivity in human offspring, we performed a longitudinal study including four assessments of infant cortisol reactivity to stressful events in a non-clinical population. General and pregnancy-related feelings of stress and anxiety, as well as circadian cortisol levels, were measured in 173 mothers in the last trimester of pregnancy. Infant cortisol reactivity was measured at 5 weeks to a bathing session, at 8 weeks to a vaccination, at 5 months to a stressful mother–infant interaction (still face procedure), and at 12 months to a maternal separation (strange situation procedure). Maternal prenatal fear of bearing a handicapped child was a consistent predictor of infant cortisol reactivity. Although the effects were mild, higher fear was significantly related to higher salivary cortisol reactivity to the bathing session and to decreased cortisol reactivity to vaccination and maternal separation. Thus, pregnancy-specific anxieties predict infant cortisol reactivity in the first year of life, but the direction of the effect depends on infant age and/or the nature of the stressor. While this specific anxiety was a better predictor than stress experience or maternal cortisol concentrations, the underlying mechanisms of these associations remain unclear. Future studies should try to incorporate multiple measures of HPA-axis reactivity during development when studying the long-term consequences of maternal prenatal stress.

Cortisol in the first year of life: Normative values and intra-individual variability

INTRODUCTION Many studies have incorporated cortisol measurements when studying infant development, but descriptions of normal development of basal cortisol levels in large study populations are scarce. The present study aimed to establish norm values for infant basal cortisol levels and to examine the development of intra-individual variability in the first year of life. METHODS More than 2500 cortisol samples were collected in 300 infants at three different ages. At each age four 1100h samples were collected to determine average cortisol levels and intra-individual variability. The development of basal cortisol levels and intra-individual variability was analyzed with multilevel growth curve modeling. RESULTS Norm tables with 90 and 95% intervals are presented. Basal cortisol levels decreased gradually over the year. Intra-individual variability was relatively large and stable in the first half year but decreased towards the end of the year. CONCLUSIONS The results of this study will aid researchers in evaluating cortisol data collected in early infancy. It also underscores the importance of taking intra-individual cortisol variability into account in studies involving infants.

Attachment and infant night waking: a longitudinal study from birth through the first year of life.

Objective: Night wakings are common in infancy. Although a link between infant night wakings and attachment to the primary caregiver has been previously proposed, empirical support is limited so far. The aim of this longitudinal study was to examine the early history of night waking in infants who were later classified as securely or insecurely (avoidantly, resistantly, or disorganized) attached. Methods: Participants in the study were 193 infants and their mothers. Information on infant night wakings was collected with the use of daily sleep diaries for the first 6 months of life and again for 2 weeks at 12 months of age. Infant-mother attachment was assessed using the Strange Situation (Ainsworth et al, Patterns of Attachment: A Psychological Study of the Strange Situation. New York: Hillsdale; 1978) when the infants were 12 months of age. Results: Longitudinal regression analyses showed that, after controlling for many covariates, infants with an insecure-resistant attachment at 12 months of age awoke more during the night in their first 6 months of life than the other infants. Furthermore, infants with different attachment classifications developed different patterns of night wakings over the first 6 months, with the insecure-avoidant infants waking the least toward the end of the 6 months. Hierarchical multiple regression analyses showed no associations between attachment and night wakings at 12 months of age. Conclusion: This study is the first in showing that attachment at 12 months of age is related to infant night waking patterns in the first 6 months of life. Patterns of infant night wakings early in life apparently reflect the emerging attachment relationship.

Explicit and implicit caregiving interests in expectant fathers: Do endogenous and exogenous oxytocin and vasopressin matter?

Caregiving interest in men (N=46) during the third trimester of their partners pregnancy was examined. The study included both explicit and implicit measures of caregiving interest, assessments of basal urinary concentrations of oxytocin and vasopressin, and exogenous (intranasal) application of these hormones. Compared to control men (N=20), fathers-to-be reported more interest in direct care for children. In an immersive virtual environment, fathers-to-be, in comparison to control men, stood closer to and tended to spend more time looking at the baby-related avatars, and stood further away and tended to spend less time looking at non-baby-related avatars. Basal oxytocin and vasopressin were not related to caregiving interest in fathers-to-be, and were not different from control men. When vasopressin was administered, fathers-to-be invested more time watching the baby-related avatars compared to control men. No effects were found of exogenous oxytocin on the behavior of fathers-to-be and control men in the immersive virtual environment. These results point in the direction of an adjustment of fathers-to-be for fatherhood, both consciously and unconsciously, and support the possible role of vasopressin in human behavior in the transition to fatherhood.

Development of the cortisol circadian rhythm in the light of stress early in life.

The secretion of the stress hormone cortisol follows a diurnal circadian rhythm. There are indications that this rhythm is affected by stress early in life. This paper addresses the development of the cortisol circadian rhythm between 1 and 6 years of age, and the role of maternal stress and anxiety early in the childs life on this (developing) rhythm. Participants were 193 healthy mother-child dyads from a community sample. Self-reported maternal stress and anxiety and physiological stress (saliva cortisol), were assessed prenatally (gestational week 37). Postnatally, self-reported maternal stress and anxiety were measured at 3, 6, 12, 30, and 72 months. Saliva cortisol samples from the children were collected on two days (four times each day) at 12, 30, and 72 months of age. The total amount of cortisol during the day and the cortisol decline over the day were determined to indicate childrens cortisol circadian rhythm. Multilevel analyses showed that the total amount of cortisol decreased between 1 and 6 years. Furthermore, more maternal pregnancy-specific stress was related to higher total amounts of cortisol in the child. Higher levels of early postnatal maternal anxiety were associated with flatter cortisol declines in children. Higher levels of early postnatal maternal daily hassles were associated with steeper child cortisol declines over the day. These results indicated developmental change in childrens cortisol secretion from 1 to 6 years and associations between maternal stress and anxiety early in childrens lives and childrens cortisol circadian rhythm in early childhood.

Cortisol reactions to a social evaluative paradigm in 5- and 6-year-old children

The goal of the present study was to develop a stress paradigm to elicit cortisol secretory responses in a group of 5- and 6-year-old children as a whole. To this end, we tested a paradigm containing elements of social evaluative threat, unpredictability and uncontrollability, and with a duration of 20 min. The Childrens Reactions to Evaluation Stress Test is composed of three short tasks that children have to perform in front of a judge. The tasks are rigged so as to provoke (partial) failure in the childs performance. Participants were 42 children (M = 68.0 months, SD = 4.3). Six saliva samples were taken during the testing session to obtain cortisol measurements of baseline concentrations, stress reactivity, and recovery. Our findings showed that this paradigm was effective in provoking a significant increase in salivary cortisol concentration in the group as a whole, with no effects of possible confounders (childs sex, age or school, parental educational level, time of testing, sex of experimenter, and sex of judge). The mean cortisol concentration increase for the group was 127.5% (SD = 190.9); 61% of the children could be classified as reactors (mean increase of 214%, SD = 201.5), and 39% as non-reactors (mean decrease of 7.8%, SD = 16.8). To our knowledge, this is the first study in this age group that shows a significant cortisol response for the group as a whole to a standardized laboratory paradigm. As such, this paradigm is a promising tool to be used in future research on early life interactions between physiology and psychology.

Exploring temperamental differences in infants from the USA and the Netherlands

This longitudinal study employed the Infant Behaviour Questionnaire-Revised in assessing temperamental differences between infants at 6 months (n = 114 US, 184 Dutch) and 12 months (n = 92 US, 172 Dutch) from the USA and the Netherlands. Main effects indicated that Dutch infants were rated higher on the Orienting/Regulatory Capacity (ORC) factor and fine-grained dimensions of smiling and laughter, falling reactivity, cuddliness, low-intensity pleasure, and soothability, whereas US infants received higher ratings on the Negative Affectivity factor and on dimensions of activity level, vocal reactivity, fear, frustration, and sadness. Cultural differences for ORC were more pronounced in early infancy, cultural differences for Fear were stronger in late infancy, and US infants demonstrated higher duration of orienting at 12 months only. Culture also appeared to impact the pace of consolidation of temperamental characteristics, with greater stability exhibited by US than Dutch infants in smiling and laughter and vocal reactivity.