inÔ¬‚uences on the fetus have been described as programming, a process by which a
stimulus or insult during a critical developmental period has a long-lasting or per-
manent inÔ¬‚uence (Nathanielsz, 1999). Animal models illustrate that maternal
stress has programming inÔ¬‚uences on development that persist not only through
adulthood, but may have transgenerational effects (Francis et al., 1999).
The human fetus is sensitive to the effects of maternal stress and furthermore,
these inÔ¬‚uences can be measured. Our program of research indicates that maternal
activation of the HPA axis is associated with adverse birth outcomes and altered
fetal responsiveness to stimulation. Additionally, prenatal stress and exposure to
stress hormones has deleterious consequences for the developing infant. We have
shown that while birth outcomes such as premature delivery can contribute to
developmental impairments, stress and stress hormones have an independent
effect on development. Our current projects extend these Ô¬Āndings to understand
the inÔ¬‚uence of the timing of stress on the fetus, the biological processes associated
with stress and the pre- and postnatal developmental consequences of prenatal stress.
One objective is to extend our ability to predict adverse outcomes such as pre-
mature birth. The magnitude of the effect of prenatal stress is comparable to that
of other established obstetric risk factors. The speciÔ¬Ācity and sensitivity of these
measures as predictors of adverse outcome(s) in any individual pregnancy is mod-
est. For example, low levels of placental CRH in pregnancy are a good negative
195 InÔ¬‚uence of stress in human fetal and infant development
predictor of preterm birth but high levels are a poor positive predictor. This may
suggest that parameters such as stress and placental CRH should be considered in
conjunction with other risk factors.
In addition to the maternal‚Ä“placental‚Ä“fetal neuroendocrine processes discussed
above, host (maternal and/or fetal) proinÔ¬‚ammatory immune responses produced
by intrauterine or reproductive tract infection have been implicated in adverse
fetal outcomes, especially extreme prematurity ( 30 weeks gestation) and white
matter brain damage (Romero et al., 2001). Although psychosocial stress is a well-
established contributor to the risk of infection and its pathophysiological conse-
quences (Cohen et al., 1999) and the endocrine and immune systems are known
to extensively regulate and counter-regulate one another (McEwen et al., 1997; Shanks
and Lightman, 2001; Elenkov and Chrousos, 2002), very little empirical work has
been done to date to examine these interactions in the context of stress in preg-
nancy and fetal development. Thus, one of our current, ongoing studies is designed
to examine psychoneuroendocrine‚Ä“immune interactions in human pregnancy, to
explore the hypothesis that maternal psychosocial stress and neuroendocrine stress
responses may play a role in determining susceptibility to the development of
reproductive tract infection and its pathophysiological consequences. We suggest this
is a critical future direction for this work as the effect of either of these processes
on a biological outcome of interest is modulated by the state/context of the other.
Returning to the concept of an epigenetic framework of development, it appears
that embryonic and fetal developmental processes ultimately represent the dynamic
interplay between two sets of information systems, fetal and maternal deoxyribo-
nucleic acid (DNA) and the fetal and maternal environments. Genetic predisposi-
tions may make some pregnancies more vulnerable to environmental inÔ¬‚uences.
We are not aware of any studies to date that have systematically examined the phys-
iological genomics of maternal and fetal stress-related neuroendocrine systems
and pathways in human pregnancy, and suggest this is yet another important
future avenue for this line of research.
In conclusion, there is a compelling need to arrive at a better understanding of
the determinants of individual differences in psychoneuroendocrine processes that
underlie health and disease. The study of the interplay between biological and
behavioral processes in fetal life, using a dynamic systems approach, holds great
promise for our efforts to arrive at this understanding.
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