Council on Environmental Health
Article Review

Prepared by: Heather L. Brumberg, MD, MPH
May 2010

TITLE
Prenatal Maternal Stress and Cord Blood Innate and Adaptive Cytokine Responses in an Inner-city Cohort

AUTHORS
Rosalind J. Wright, Cynthia M. Visness, Agustin Calatroni, Mitchell H. Grayson, Diane R. Gold, Megan T. Sandel, Aviva Lee-Parritz, Robert A. wood, Meyer Kattan, Gordon R. Bloomberg, Melissa Burger, Alkis Togias, Frank R. Witter, Rhoda S. Sperling, Yoel Sadovsky, James E. Gern

FIND IT AT
http://ajrccm.atsjournals.org/cgi/content/abstract/200904-0637OCv1

THE PROBLEM
Asthma and other atopic disease rates continue to rise.  These diseases have many possible etiologies, among which immunologic causes have been noted.  A key component of the human immune system are the T-helper cells (type 1 and 2) which are normally in balance.  The Th1 (or type 1 T-helper) pathway stimulation is important for cell mediated immunity and is responsible for increases in cytokines such as Interlukin-2 and Interferon-γ.  On the other hand, the Th2 (or type 2 T-helper) cascade is related to the humoral pathway and can thus stimulate IgE production.  One important contributor to allergy and atopic disease is felt to be when the Th2 pathway predominates.  One prenatal mechanism in which the Th2 pathway is stimulated and Th1 is diminished is hypothesized to be maternal stress through increased glucocorticoids and epinephrine.  There is little information in humans, however, demonstrating this link between prenatal stress and neonatal immune response.

WHAT THEY DID
Researchers examined cord blood mononuclear cell cytokine profiles after stimulation and compared immune response with maternal levels of stress.  The study population was derived from the Urban Environment and Childhood Asthma (URECA) prospective birth cohort.  This cohort contains 557 families (enrolled from 2/05-3/07) with pregnant mothers residing in Baltimore, Boston, New York, and St. Louis, living in an area with >20% of residents below poverty level, having a history of parental atopy, and the baby when born needed to be >34 weeks gestation to be included.  The exposure of maternal stress was assessed with a survey reflecting difficult life circumstances such as domestic violence, economic strain such as not having enough food, neighborhood/block conditions such as gang presence, perceived community violence such as recent robbery in the neighborhood, and housing worries such as concern of eviction.  The cord blood mononuclear cells were incubated with innate (such as lipopolysaccharide) and adaptive (such as dust mite antigen) stimuli, and the resultant cytokine production was measured and correlated with a cumulative maternal stress score.

WHAT THEY FOUND
Both innate and adaptive immune responses were heightened with increased maternal stress.  Specifically, in the adaptive panel the responses were consistent with a predominant activation of the Th2 pathway (as indicated by higher IL-13 and lower interferon-γ).  Overall, higher maternal stress levels were positively correlated with increased immune responses.

DISCUSSION
This is the first human study demonstrating a correlation between maternal stress and altered neonatal immune responses as measured through cord blood assays for cytokines.  This study helps substantiate that the social environment which a pregnant mother is exposed to can directly influence the neonatal immune system.  Perhaps these cytokine profiles that suggest a higher Th2 pathway predominance help to explain higher asthma and atopy in poor urban environments.  Follow-up of these neonates to determine long term outcomes such as prevalence of asthma would help to further support the connection between maternal stress and childhood asthma.

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