Lower cortisol levels in children with asthma exposed to recurrent maternal distress from birth

doi:10.1016/j.jaci.2009.09.051

Journal of Allergy and Clinical Immunology

Volume 125, Issue 1, January 2010, Pages 116-122

https://doi.org/10.1016/j.jaci.2009.09.051 Get rights and content

Background

Existing evidence supports associations between exposure to maternal distress and the development of childhood asthma, between exposure to maternal distress and an increased cortisol response in children, and between childhood asthma and an attenuated cortisol response.

Objective

To investigate the association between children's cortisol levels and the combined predictors of exposure to maternal distress and childhood asthma.

Methods

Serum cortisol levels were examined at age 7 to 10 years in relation to asthma status and exposure to maternal distress in a representative sample of children (n = 503) born in 1995. Data from health care and prescription databases were linked with additional data collected in this longitudinal study. Maternal distress was defined as a physician diagnosis of a depressive or anxiety disorder or a prescription history of related medications as reported in the mothers' health care records. Children's asthma status was determined via examination by 2 pediatric allergists.

Results

A multiple linear regression analysis revealed that exposure to maternal distress restricted to the first year of life predicted elevated cortisol levels in children, regardless of asthma status (>40% increase). A significant interaction was discovered in the group of children exposed to maternal distress extending beyond the postnatal period such that no asthma predicted a 25.9% increase in cortisol and a diagnosis of asthma predicted a 5.2% decrease in cortisol. Cortisol levels were further lowered in atopic and bronchial hyperresponsive asthma.

Conclusion

Among children exposed to recurrent maternal distress, an elevation in cortisol levels occurs in response to an acute stressor when there is no accompanying diagnosis of asthma, whereas, in comparison, children with asthma tend to exhibit lower cortisol levels.

Section snippets

Participants

This was a study of a sample of Manitoba children born in 1995 who were selected for a nested case-control study in the project Study of Asthma, Genes, and the Environment (SAGE). The SAGE study design is described elsewhere.¹⁰ Plasma aliquots for cortisol level determinations were available for 507 of the 723 blood samples obtained from SAGE children at age 7 to 10 years. Informed consent and child assent was obtained from all participating families, including permission to access provincial

Results

The final sample consisted of 503 children, 315 with no asthma and 188 with an asthma diagnosis. Of the children without asthma, 170 (54 %) were boys, and the mean age was 8.59 years (SD, .59). In the group of children with asthma, 113 (60.1%) were boys, and the average age was 8.27 years (SD, .60). The distribution of all variables included in the study can be seen in Table II. Children with asthma had significantly more physician visits since birth and a higher percentage of corticosteroid

Discussion

In our population-based study of 503 schoolchildren, children exposed to maternal distress restricted to their first year of life responded to an acute stressor with elevated cortisol levels, regardless of their asthma status. In those exposed to recurrent maternal distress since birth, having no asthma predicted a 26% elevation in cortisol levels. Children with asthma exhibited a lower cortisol response to the acute stressor, seen as a 5.2% decrease in plasma cortisol. Cortisol levels were 13%

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Prior studies indicate that stress, anxiety, and worsened asthma symptoms are related to one another (Theoharides et al., 2012). For example, in children exposed to persistent maternal distress in early life, those with asthma have significantly decreased plasma cortisol compared to children without asthma (Dreger et al., 2010). Further, baseline and reactivity levels of cortisol in youth with asthma predicts neuropsychological functioning in subsequent years (Dinces et al., 2019).
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The greater influence of chronic vs short-term postpartum depression on cortisol levels in preschool-aged children is well known.39 Recurrent maternal depression or anxiety from childbirth can also lead to altered cortisol levels and higher allostatic load in children, as well as a heightened risk of asthma in boys.40,41 We also observed that late-onset postnatal distress had a stronger impact on the development of asthma and atopy in male children than in female children.
Early-life stress is becoming an important determinant of immune system programming. Maternal prenatal distress is found to be associated with atopic disease in offspring but the separate effects of postnatal distress are not well-studied.
Does the likelihood of asthma and atopic dermatitis in children increase when they are exposed to maternal distress pre- and postnatally in a sex-specific manner?
Using data from a provincial newborn screen and health-care database for 12,587 children born in 2004, maternal distress (depression or anxiety) was defined as prenatal, self-limiting, recurrent, or late-onset postpartum. Atopic dermatitis (AD) and asthma at ages 5 years and 7 years of age were diagnosed by using hospitalization, physician visit, or prescription records. Associations between maternal distress and childhood asthma and AD were determined by using multiple logistic regression.
After adjusting for risk factors, a significant association between maternal prenatal (OR, 1.27; 95% CI, 1.11-1.46), recurrent postpartum (OR, 1.28; 95% CI, 1.11-1.48), and late-onset postpartum (OR, 1.19, 95% CI, 1.06-1.34) distress was found with AD at age 5 years. Asthma at age 7 years was also associated with maternal prenatal distress (OR, 1.57; 95% CI, 1.29-1.91) and late-onset postnatal distress (OR, 1.22; 95% CI, 1.01-1.46). Self-limiting postnatal distress was not found to be a risk factor for either atopic condition. Associations with AD or asthma were of a similar magnitude in boys and girls; the exception was recurrent postnatal distress, which increased risk for asthma in boys only.
This population-based study provides evidence for sex-specific associations between maternal prenatal and postnatal distress, as well as the development of AD and asthma. The findings support recommendations for greater psychosocial support of mothers during pregnancy and early childhood to prevent childhood atopic disease.
Hair cortisol concentration mediates the association between parent and child psychopathology
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The mediating effect is sex-based; it is more pervasive among boys, but specific to major depressive episode and attention-deficit hyperactivity disorder among girls. Similar to a previous study of children with asthma (Dreger et al., 2010), our findings provide evidence that children with mental illness have an intergenerational continuity, perhaps via a shared (epi)genetic factor, to the psychopathology of their parents. Generally, our findings that HCC was a mediator were consistent with a previous report using salivary cortisol as a mediator of maternal major depressive disorder and child symptoms of internalizing and externalizing problems (Ulmer-Yaniv et al., 2018).
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Maternal depressive symptoms linked to reduced fecal Immunoglobulin A concentrations in infants
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Secretory Immunoglobulin A (sIgA) plays a critical role to infant gut mucosal immunity. Delayed IgA production is associated with greater risk of allergic disease. Murine models of stressful events during pregnancy and infancy show alterations in gut immunity and microbial composition in offspring, but little is known about the stress-microbiome-immunity pathways in humans. We investigated differences in infant fecal sIgA concentrations according to the presence of maternal depressive symptoms during and after pregnancy. A subsample of 403 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort were studied. Their mothers completed the Center of Epidemiologic Studies Depression Scale when enrolled prenatally and again postpartum. Quantified by Immundiagnostik sIgA ELISA kit, sIgA from infant stool was compared across maternal depressive symptom categories using Mann-Whitney U-tests and logistic regression models that controlled for various covariates. Twelve percent of women reported clinically significant depressive symptoms only prenatally, 8.7% had only postpartum symptoms and 9.2% had symptoms both pre and postnatally. Infants born to mothers with pre and postnatal symptoms had significantly lower median sIgA concentrations than those in the reference group (4.4 mg/g feces vs. 6.3 mg/g feces; p = 0.033). The odds for sIgA concentrations in the lowest quartile was threefold higher (95% CI: 1.25–7.55) when mothers had pre and postnatal symptoms, after controlling for breastfeeding status, infant age, antibiotics exposure and other covariates. Postnatal symptoms were not associated with fecal sIgA, independently of breastfeeding status. Infants born to mothers with depressive symptoms appear to have lower fecal sIgA concentrations, predisposing them to higher risk for allergic disease.
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: Supported by AllerGen NCE Inc and province of Manitoba NCE support, the Canadian Institutes of Health Research (New Emerging Team Program, Study of Asthma, Genes, and the Environment), and the Social Sciences and Humanities Research Council (Canada Graduate Scholarship).

: Disclosure of potential conflict of interest: K. T. HayGlass, A. L. Kozyrskyj, and A. B. Becker received research support from the Canadian Institutes of Health Research. The rest of the authors have declared that they have no conflict of interest.

View full text

Asthma and lower airway diseaseLower cortisol levels in children with asthma exposed to recurrent maternal distress from birth

Background

Objective

Methods

Results

Conclusion

Section snippets

Participants

Results

Discussion

Biol Psychiatry

J Allergy Clin Immunol

J Allergy Clin Immunol

Infant Behav Dev

Psychoneuroendocrinology

Horm Behav

Psychoneuroendocrinology

Biol Psychiatry

Biol Psychiatry

Trends Endocrinol Metab

Psychoneuroendocrinology

Biol Psychol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Biochim Biophys Acta

Paediatr Respir Rev

Psychoneuroendocrinology

Psychoneuroendocrinology

Parental stress as a predictor of wheezing in infancy: a prospective birth-cohort study

Am J Respir Crit Care Med

Onset and persistence of childhood asthma: predictors from infancy

Pediatrics

Continued exposure to maternal distress in early life increases the risk of childhood asthma

Am J Respir Crit Care Med

Asthma and lower airway disease
Lower cortisol levels in children with asthma exposed to recurrent maternal distress from birth