MISSION

factor-1 (COUP-TF1/Nr2f1), all of which could decrease RA signaling. Their recent studies have demonstrated
that the decreased RARE activation is associated with decreased nuclear extract binding to the most
abundant RARE, DR5.
Given the effects on RA component expression and their in vitro studies showing decreased function of
the RA pathway following cigarette smoke exposure, Dr. Haley and colleagues hypothesized that gestational
tobacco smoke would cause decreased expression of RA-dependent genes in the postnatal lung. They
subjected RNA extracted from lung tissue in mice, with and without gestational tobacco smoke exposure,
to quantitative PCR analysis to test this hypothesis. Their analysis showed that gestational SHS exposure
caused decreased expression of surfactant protein B and vascular endothelial growth factor, which are both
important for alveolar development and maturation. Their recent studies demonstrated that extra-pulmonary
RA-regulated processes, such as T regulatory cell development, are also adversely affected by
intrauterine cigarette smoke exposure. Additionally, they have shown that intrauterine smoke exposure
causes abnormalities in a second nuclear receptor pathway, the vitamin D signaling pathway. Thus, their
studies have demonstrated that in utero exposure to SHS disrupts the expression and function of the RA
and vitamin D signaling pathways in the developing lung and results in abnormalities in RA-dependent
processes in the postnatal animal.
MATERNAL SMOKING: FETUSES IN WITHDRAWAL?
Laura Stroud, PhD; The Miriam Hospital, Brown University; CIA 2007
Little is known regarding effects of maternal smoking during pregnancy on offspring behavior during
the fetal and newborn periods. One key unanswered question is whether exposure to maternal cycles of
daytime smoking and overnight abstinence results in symptoms of withdrawal/abstinence in the fetus. This
study is the first to examine the possibility of a fetal withdrawal syndrome from exposure to maternal
smoking. The aims are to characterize 1) differences in fetal behavior and withdrawal symptoms following
maternal smoking versus overnight abstinence; 2) links between fetal and newborn behavior; and 3) effects
of SHS exposure on fetal and infant behavior. Dr. Stroud and colleagues have pioneered use of ultrasound
technology to evaluate fetal behavior including withdrawal symptoms. In this ongoing study, these techniques
are applied to examine the possibility of a smoking-related fetal withdrawal process. Smoking and
non-smoking mothers matched on socioeconomic status, alcohol use, race, and age are being recruited
through an ongoing longitudinal study of prenatal smoking and infant withdrawal. Mothers complete two
fetal behavioral examinations including measures of withdrawal. Smoking mothers complete one exam following
overnight abstinence and another following ad libitum smoking. Infant neurobehavior and withdrawal
are assessed over the first 30 days of life.
Preliminary results from the fetal ultrasound data showed, as expected, that carbon monoxide (CO) levels
were significantly higher for smokers versus non-smokers for the fetal session following ad libitum
smoking (F = 10.5, p< .01). They also found a significant smoking group by time interaction for CO
levels (F = 22.9, p< .001), such that a significant decrease in CO levels emerged for smokers between ad
libitum and abstinence sessions but no differences in CO levels emerged for non-smokers. Dr. Stroud and
colleagues also conducted some preliminary analyses in support of the three study aims. For Aim 1, consistent
with their hypothesis of differences in fetal behavior in smoking-exposed versus unexposed fetuses,
they found greater reactivity to the vibro-acoustic stimulus (VAS; 100% reactive versus 50% reactive across
both fetal sessions), shorter latency to react (M’s = 45 vs. 155 seconds for the fetal session following
overnight abstinence), and faster recovery (M’s = 45 vs. 153 seconds across both fetal sessions) in exposed
relative to unexposed fetuses. For Aim 2, they found high-magnitude inverse correlations between seconds
to respond to the VAS and scores on the withdrawal scale of the infant neurobehavioral examination in the
first days of life (r’s = .26-.76) such that shorter latency to respond to the VAS was associated with greater
signs of neonatal withdrawal. For the exploratory aim, they found high magnitude associations between
maternal SHS exposure during pregnancy and latency to react to the VAS (r’s = .36-.46) such that greater
exposure was associated with longer latency to respond to the VAS. Results are preliminary but suggest
strong associations between maternal smoking and exposure to SHS and fetal and infant behavior. Results
from this study will lead to critical advances in determining mechanisms underlying effects of prenatal
smoking exposure. Results also have important clinical and public health implications, including early identification
and targeted intervention efforts to protect offspring at risk for later adverse outcomes and novel
intervention efforts to help pregnant smokers quit.
FAMRI Supported Publications
Crespo F, Lense M, Salisbury A, Stroud LR. Maternal smoking and fetal neurobehavior: a pilot study.
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