Evolutionary-biological reasoning suggests that individuals should be differentially susceptible to environmental influences, with some people being not just more vulnerable than others to the negative effects of adversity, as the prevailing diathesis-stress view of psychopathology (and of many environmental influences) maintains, but also disproportionately susceptible to the beneficial effects of supportive and enriching experiences (or just the absence of adversity). Evidence consistent with the proposition that individuals differ in plasticity is reviewed. The authors document multiple instances in which (a) phenotypic temperamental characteristics, (b) endophenotypic attributes, and (c) specific genes function less like “vulnerability factors” and more like “plasticity factors,” thereby rendering some individuals more malleable or susceptible than others to both negative and positive environmental influences. Discussion focuses upon limits of the evidence, statistical criteria for distinguishing differential susceptibility from diathesis stress, potential mechanisms of influence, and unknowns in the differentialsusceptibility equation.

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Beyond Diathesis Stress: Differential Susceptibility to Environmental Influences.

We review a significant body of evidence from independent prospective studies that if a mother is stressed while pregnant, her child is substantially more likely to have emotional or cognitive problems, including an increased risk of attentional deficit/hyperactivity, anxiety, and language delay. These findings are independent of effects due to maternal postnatal depression and anxiety. We still do not know what forms of anxiety or stress are most detrimental, but research suggests that the relationship with the partner can be important in this respect. The magnitude of these effects is clinically significant, as the attributable load of emotional/behavioral problems due to antenatal stress and/or anxiety is approximately 15%. Animal models suggest that activity of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis and its hormonal end-product cortisol are involved in these effects in both mother and offspring. The fetal environment can be altered if stress in the mother changes her hormonal profile, and in humans, there is a strong correlation between maternal and fetal cortisol levels. However, many problems remain in understanding the mechanisms involved in this interaction. For example, maternal cortisol responses to stress decline over the course of pregnancy, and earlier in pregnancy, the link between maternal and fetal cortisol is less robust. It is possible that the effects of maternal anxiety and stress on the developing fetus and child are moderated by other factors such as a maternal diet (e.g., protein load). It is suggested that extra vigilance or anxiety, readily distracted attention, or a hyper-responsive HPA axis may have been adaptive in a stressful environment during evolution, but exists today at the cost of vulnerability to neurodevelopmental disorders.

Antenatal maternal stress and long-term effects on child neurodevelopment: how and why?

Objective: We developed clinical practice guidelines for congenital adrenal hyperplasia (CAH).

Participants: The Task Force included a chair, selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), ten additional clinicians experienced in treating CAH, a methodologist, and a medical writer. Additional experts were also consulted. The authors received no corporate funding or remuneration.

Consensus Process: Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society’s CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments.

Conclusions: We recommend universal newborn screening for severe steroid 21-hydroxylase deficiency followed by confirmatory tests. We recommend that prenatal treatment of CAH continue to be regarded as experimental. The diagnosis rests on clinical and hormonal data; genotyping is reserved for equivocal cases and genetic counseling. Glucocorticoid dosage should be minimized to avoid iatrogenic Cushing’s syndrome. Mineralocorticoids and, in infants, supplemental sodium are recommended in classic CAH patients. We recommend against the routine use of experimental therapies to promote growth and delay puberty; we suggest patients avoid adrenalectomy. Surgical guidelines emphasize early single-stage genital repair for severely virilized girls, performed by experienced surgeons. Clinicians should consider patients’ quality of life, consulting mental health professionals as appropriate. At the transition to adulthood, we recommend monitoring for potential complications of CAH. Finally, we recommend judicious use of medication during pregnancy and in symptomatic patients with nonclassic CAH.

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Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline

The Adaptive Calibration Model of stress responsivity.

Purpose of reviewTo briefly review results of the latest research on the contributions of depression, anxiety, and stress exposures in pregnancy to adverse maternal and child outcomes, and to direct attention to new findings on pregnancy anxiety, a potent maternal risk factor.Recent findingsAnxiety,

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Anxiety, depression and stress in pregnancy: implications for mothers, children, research, and practice.

Objective To examine the effects of prenatal stress on cognition and behavioral fearfulness in infants. Method Mothers were recruited at amniocentesis at Queen Charlotte's and Chelsea Hospital, London, between 2001 and 2005, and recalled when their children were 14 to 19 months to assess cognitive development using the Bayley Scales and fearfulness using the Lab-TAB. Measures of prenatal and postnatal life events and current psychological state were collected at the postnatal visit. Results Prenatal stress predicted both mental development ( r s = −0.39, n = 123 p r s = 0.33, n = 106, p r = −0.06, not significant). Prenatal partner relationship strain accounted for 73.5% and 75.0% of the prenatal stress related variance on infant cognitive and fearfulness scores, respectively. Conclusions These findings strengthen previous research that suggests that fetal programming can be important for neurodevelopmental and psychiatric outcomes. They imply that the mechanisms by which mental development and fearfulness are affected are different and that prenatal stress due to relationship strain may warrant particular attention.

Maternal stress during pregnancy predicts cognitive ability and fearfulness in infancy.

Maternal Prenatal Cortisol and Infant Cognitive Development: Moderation by Infant-Mother Attachment

Association between maternal and amniotic fluid cortisol is moderated by maternal anxiety

Experimental animal findings suggest that early stress and glucocorticoid exposure may program the function of the hypothalamic-pituitary-adrenal (HPA) axis in the offspring. The extension of these findings to human development is not yet clear. A prospective longitudinal study was conducted on 125 mothers and their normally developing children. Amniotic fluid was obtained at, on average, 17.2 weeks gestation; infant behavior and cortisol response to a separation-reunion stress was assessed at 17 months. Amniotic fluid cortisol predicted infant cortisol response to separation-reunion stress: infants who were exposed to higher levels of cortisol in utero showed higher pre-stress cortisol values and blunted response to stress exposure. The association was independent of prenatal, obstetric, and socioeconomic factors and child-parent attachment. The findings provide some of the strongest data in humans that HPA axis functioning in the child may be predicted from prenatal cortisol exposure.

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Prenatal Cortisol Exposure Predicts Infant Cortisol Response to Acute Stress

Both animal and human studies have shown that maternal stress or anxiety during pregnancy is associated with increased risk of disturbance in offspring neurodevelopment and behaviour. In animal models, increased foetal exposure to glucocorticoids has been found to be one mechanism for such foetal programming. Little is understood of the mediating mechanisms in humans, and one aim of our research programme is to investigate this further. This review presents a synopsis of some of our recent results. We aimed to test the hypothesis that maternal anxiety was associated with raised maternal cortisol, and that this in turn was related to increased foetal exposure to cortisol. We studied this by recruiting women at amniocentesis, obtained their Spielberger State Anxiety scores, and assessed maternal plasma cortisol and amniotic fluid cortisol. We also examined maternal plasma and amniotic fluid testosterone levels. Awaiting amniocentesis was in general anxiogenic, but with a wide range of anxiety scores. Maternal anxiety was significantly associated with plasma cortisol before 17 weeks, albeit of modest magnitude (r = 0.0.23), and not after 17 weeks of gestation. This is probably due to the known attenuation of the maternal hypothalamic-pituitary-adrenal axis with increasing gestation. We found a strong correlation between maternal plasma and amniotic fluid cortisol levels, which increased with gestation and became robust after 18 weeks. This correlation increased with maternal anxiety, suggesting a possible effect of maternal mood on placental function. There was a positive correlation between cortisol and testosterone in amniotic fluid, in both male and female foetuses independent of maternal anxiety, plasma testosterone, gestational age, and time of collection. Foetal stress may be associated with increased foetal exposure to testosterone. However, maternal anxiety did not predict amniotic fluid cortisol or testosterone level. Thus, the role of these hormones in mediating the effect of maternal mood on foetal development in humans remains to be demonstrated.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2826.2008.01659.x

Kristin Bergman

Papers

Maternal stress during pregnancy predicts cognitive ability and fearfulness in infancy.

Maternal Prenatal Cortisol and Infant Cognitive Development: Moderation by Infant-Mother Attachment

Association between maternal and amniotic fluid cortisol is moderated by maternal anxiety

Prenatal Cortisol Exposure Predicts Infant Cortisol Response to Acute Stress

Maternal antenatal anxiety and amniotic fluid cortisol and testosterone: possible implications for foetal programming.