Psychoneuroendocrinology (2004) 29, 1028–1036
www.elsevier.com/locate/psyneuen
Effects of prenatal betamethasone exposure
on regulation of stress physiology in healthy
premature infants
Elysia Poggi Davisa,*, Elise L. Townsendb, Megan R. Gunnarb,
Michael K. Georgieffb,c, Sixto F. Guiangc, Raul F. Ciffuentesd,
Richard C. Lusskyd
a
Department of Psychiatry and Human Behavior, University of California Irvine, City Tower,
333 City Boulevard West, Orange, CA 92868, USA
b
Institute of Child Development and the Center for Neurobehavioral Development,
University of Minnesota, 51 East Rover Road, Minneapolis, MN 55455, USA
c
Department of Pediatrics, D-136 Mayo, 420 Delaware St SE, University of Minnesota, Minneapolis,
MN 55455, USA
d
Department of Pediatrics—867B, Hennepin County Medical Center, 701 Park Avenue South,
Minneapolis, MN 55415, USA
Received 18 October 2002; received in revised form 4 September 2003; accepted 20 October 2003
KEYWORDS
Cortisol; Stress; HPA
axis; Prematurity;
Prenatal experience;
Betamethasone
*
Summary The objective of this study was to examine the effects of prenatal
exposure to betamethasone, a corticosteroid, on postnatal stress regulation, particularly activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. Effects
were assessed by measuring salivary cortisol production at baseline and in response
to two potentially stressful events, a heel-stick blood draw and a physical exam, in
infants born at 33–34 weeks gestation. Subjects included 9 infants with antenatal
betamethasone treatment (2 doses of 12 mg of betamethasone administered intramuscularly to the mother twelve hours apart) and 9 infants without such treatment.
Testing took place 3–6 days after delivery. Measures of behavioral distress confirmed that both events were stressful to these premature infants. Infants with
betamethasone exposure, however, failed to exhibit increases in cortisol to either
stressor. In contrast, infants without betamethasone exposure displayed elevated
cortisol to the heel-stick blood draw but not the physical exam. These findings suggest that antenatal corticosteroids suppress infants’ HPA response to a stressor typically encountered in a neonatal intensive care situation.
# 2003 Elsevier Ltd. All rights reserved.
Corresponding author. Tel.: +1-714-940-1924; fax: +1-714940-1939.
E-mail address: [email protected] (E.P. Davis).
Work with rodents and nonhuman primates has
illustrated that prenatal exposure to elevated
levels of glucocorticoids has life long consequences for the regulation of the hypothalamic-
0306-4530/$ - see front matter # 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.psyneuen.2003.10.005
Prenatal Corticosteroid Exposure
pituitary-adrenocortical (HPA) axis (Levitt et al.,
1996; Matthews, 2000; Muneoka et al., 1997;
Takahashi, 1998; Uno et al., 1994; Welberg and
Seckl, 2001). The HPA axis produces cortisol,
often described as a stress hormone. Cortisol has
a multitude of physiological effects and when
released during stress enhances an organism’s
ability to adapt (McEwen, 1998; Sapolsky et al.,
2000). Regulation of the HPA axis has critical
implications for health and development.
Despite evidence for a lasting impact of prenatal exposure to corticosteroids on the functioning of the HPA axis in animals, few studies of this
phenomenon have been undertaken in human
populations (Ward and Phillips, 2001). This issue is
critical given the widespread use of corticosteroids in pregnant women at risk for premature
delivery. Antenatal corticosteroid administration
is a standard of care for women at risk of premature delivery and has been shown to reduce mortality and respiratory distress among preterm
infants born at less than 34 weeks gestation. Betamethasone, one of the two the preferred corticosteroids used for antenatal treatment, crosses the
placenta and initiates surfactant production in
fetal lungs. Surfactant production in premature
infants facilitates respiratory function with less
pharmacological and mechanical support (ACOG
Committee Opinion, 2002; Maher, Cliver, Goldenberg, Davis, & Copper, 1994; Murphy, 2001; NIH
Consensus Development Conference, 1995).
Additionally, betamethasone crosses the blood
brain barrier and thus, may impact central nervous system development (Antonow-Schlorke
et al., 2003; Trenque et al., 1994). The shortterm side effects of synthetic corticosteroids,
including betamethasone, seem to be well tolerated by preterm infants (Bettendorf et al., 1998).
However, long-term effects of steroid administration on the HPA axis are unknown (Bakker, van Bel
and Heijnen, 2001; Bettendorf et al., 1998).
Research examining the effects of antenatal
corticosteroid treatment on HPA axis regulation in
humans has focused primarily on baseline cortisol
production. Baseline cortisol levels are suppressed
for 2–7 days after prenatal corticosteroid treatment and subsequently return to normal levels
(Ballard et al., 1980; Dorr et al., 1989; Kauppila
et al., 1978; Parker et al., 1996; Wittekind et al.,
1993). These studies, however, failed to examine
the HPA response to a stressor. Only one study has
assessed the effect of antenatal corticosteroid
administration on HPA axis activation in humans.
This study employed the human corticotrophin
releasing hormone (hCRH) stimulation test. The
cortisol response to the hCRH test was suppressed
in infants who received antenatal corticosteroid
1029
treatment indicating that exposure impairs activation of the HPA axis (Ng et al., 2002). These
data raise the possibility that antenatal corticosteroids may suppress the HPA axis responsivity to
environmental stressors experienced in the neonatal intensive care unit (NICU). The effect of
antenatal corticosteroids on regulation of the HPA
response to stressors, however, has not been
examined.
The goal of the current study was to evaluate
the impact of antenatal betamethasone exposure
on cortisol levels at resting baseline and in
response to stressors typical of the NICU environment. Previous work indicates that both full term
infants (Gunnar, 1992; Gunnar et al., 1992) and
preterm infants (Magnano et al., 1992) without
antenatal corticosteroid treatment display increases in cortisol to two stressors; a physical exam
and a heel-stick blood draw. Infants, however,
respond differently to these events. Full term
infants cry less and habituate more quickly to
physical exams than heel-stick blood draws across
daily presentations, suggesting that the blood
draw is more aversive than the physical exam
(Gunnar et al., 1992).
Physical exams and heel-stick blood draws were
used as stressors to examine whether antenatal
betamethasone suppresses cortisol production.
Infants who did and did not receive antenatal
betamethasone treatment were assessed between
postnatal days three and six after stabilization of
birth-related fluctuations in basal cortisol (Stahl
et al., 1979). To determine whether antenatal
betamethasone effects were specific to the cortisol response, behavioral state and heart rate
responses to these stressors were also examined.
1. Methods
1.1. Participants
Subjects included 18 healthy premature infants
(33–34 weeks gestational age at birth). Verbal and
written consent was obtained prior to each
infant’s enrollment in the study. Consent was
obtained from 90% of parents solicited for participation. Subjects represented two groups: a no
treatment group, 9 infants (4 girls and 5 boys)
without antenatal betamethasone exposure and a
treatment group, 9 infants (4 girls and 5 boys)
whose mothers had received a single course of
antenatal betamethasone prior to delivery. Participants were recruited from two large metropolitan hospitals with neonatal intensive care units:
Fairview University Medical Center (n = 10) and
1030
Hennepin County Medical Center (n = 8) with 550
and 250 admissions per year respectively.
Only healthy infants appropriate for gestational
age were included. All infants met the following
criteria: within 2 standard deviations of the mean
length and weight for gestational age (determined
by plotting the measurements on standardized
growth curves), and absence of chromosomal or
other genetic anomalies (e.g., trisomy 21), congenital infections, chronic lung disease, mechanical ventilation over 24 hours, interventricular
hemorrhage, neonatal illness (e.g., sepsis),
maternal history of adrenal illness or endocrine
problems (e.g., diabetes), major maternal illness,
and maternal substance use during pregnancy
(e.g., alcohol).
1.1.1. Antenatal betamethasone
The decision to administer antenatal betamethasone rested entirely on the clinical judgment of
the attending obstetrician. Antenatal betamethasone was not administered to mothers of infants
in the no treatment group because delivery was
imminent1. Infants in the treatment group were
exposed to a single course of betamethasone.
Each course consisted of two doses of 12 mg of
betamethasone delivered intramuscularly to the
mother twelve hours apart. The second of the two
doses was administered between one and twentyone days prior to delivery (M = 8.3).
1.1.2. Clinical characteristics
Clinical information for infants in both groups is
described in Table 1. Mothers of the two groups of
infants did not differ in age at time of delivery,
marital status, race, reported cigarette use, or
whether they received prenatal care from an
obstetrician during the first half of pregnancy.
Infants in the two groups did not differ in one or
five-minute Apgar scores, birth weight, length, or
head circumference, method of delivery, whether
they were a singleton or fraternal twin.
1.2. Procedure
Medical history was obtained through chart
review. On two days between postnatal days three
and six, resting baseline and responses to a heelstick blood draw and a physical exam (order counterbalanced) were examined. Duration of each
stressor and the number of prior heel-sticks or
exams were recorded. Infants’ postnatal age on
1
Management guidelines for starting antenatal betamethasone therapy in women between 24 and 34 weeks gestation
were: 1) threatened preterm labor, 2) antepartum hemorrhage, 3) premature rupture of membranes, and 4) any condition requiring elective premature delivery.
E.P. Davis et al.
the heel-stick blood draw day (M = 4.1 days vs.
M = 4.3 days), t(16) = 0.29, p = 0.77, and physical
exam day (M = 5.2 days vs. M = 4.4 days), t(16) =
1.84, p = 0.09, did not differ between groups.
Each two hour testing period began one hour
after the feeding that occurred between 0400 and
0700 hours. First, infants were monitored continuously for one hour and behavioral state was
recorded at five-minute intervals. Infants were
not handled and all infants were observed to be in
either quiet or active sleep during this hour. Resting baseline cortisol, heart rate, and behavioral
state were then assessed. Thus, these measures
were taken two hours after the infant’s last feeding and after the infant was observed to be sleeping for an hour.
During the five minute resting baseline, heart
rate was collected and the infant was videotaped
for behavioral observations. Resting baseline salivary cortisol was then assessed, followed by the
event period consisting of either a physician’s
physical exam or a physician ordered heel-stick
blood draw2. Heart rate recording and videotaping
continued during the event and recovery periods.
Salivary cortisol samples were obtained 20–25
minutes and 40–45 minutes after the start of the
event.
1.3. Measures
1.3.1. Salivary cortisol
Saliva was collected without waking the infants by
placing a Q-tip2 cotton swab in the infant’s
mouth, for 5 minutes, until the cotton was saturated3. Salivary cortisol reflects the unbound or
active fraction of cortisol and is highly correlated
with plasma cortisol in premature and full term
newborns, children, and adults (Calixto et al.,
2002; Gunnar, 1989; Kirschbaum and Hellhammer,
1989; Woodside et al., 1991). The Q-tip was then
placed in a salivette2 from Sarstedt, centrifuged
(10 mins at 4000 Hz) to extract saliva and stored
in a freezer at 20 C until assayed. Saliva samples were assayed for cortisol determination
employing a competitive solid phase time-resolved
fluorescence immunoassay with flouromeric end
2
Blood draws were performed for clinically indicated reasons
and not for the purposes of this study.
3
To ensure that the cotton on the Q-tip was not interfering
with the assay saliva samples were collected from 7 adult
volunteers. Participants spit directly into the salivette to collect a ‘‘pure’’ sample. A Q-tip was then placed into the saliva
sample until saturated and then placed into a second salivette.
Salivettes were placed into a centrifuge to extract saliva and
then stored in a freezer at 20 C until assayed. Q-tip samples
were highly correlated with pure samples, r(7) = 0.985, p =
0.0001.
Prenatal Corticosteroid Exposure
1031
Table 1 The clinical characteristics of the study population
No Betamethasone
1 minute Apgar
5 minute Apgar
Birth weight (grams)
Birth length (cm)
Head circum. (cm)
Maternal age at birth
Method of delivery
Vaginal
C-section
Twins
Race
Caucasian
African American
Hispanic
Indian
Native American
Marital status
Married
Single
Mechanical ventilation < 24 hrs
Prenatal care from an obstetrician during the first trimester
Cigarette use
Betamethasone
N
M
SD
N
M
SD
p
9
9
9
9
9
9
6.9
8.2
1861.1
43.8
30.8
28.6
1.9
0.8
222.2
1.5
1.1
5.8
9
9
9
9
9
9
6.6
8.2
1958.3
44.3
30.6
28.6
1.9
1
203
2.8
1.1
4.4
ns
ns
ns
ns
ns
ns
No Betamethasone
Betamethasone
6
3
5 (2 twin pairs,
1 twin A)
5
4
6 (2 twin pairs, 1 twin A,
1 twin B)
p
ns
ns
ns
4
3
1
0
1
7
0
0
1
1
5
4
5
5
6
3
3
8
ns
ns
4
2
ns
ns
Comparisons were made using independent sample t-tests.
point detection (DELFIA) (Dressendörfer et al.,
1992). All samples from one infant were included
in the same assay batch to eliminate within subject inter-assay variance. Each batch contained
both control and betamethasone subjects. Volume
permitting, samples were assayed in duplicate and
averaged. Sixty-eight percent of the samples were
assayed in duplicate. The inter-assay and intraassay coefficients of variance were 11.99 and
4.30, respectively.
1.3.2. Heart rate
Heart rate was recorded continuously from premature infants in the NICU using either a Space Labs
or an Air Shields monitor. Heart rate was retained
for the purposes of this study at 30-second intervals during a five-minute resting baseline period
just prior to the event, during the event, and during the 5-minute recovery period. Mean heart rate
was calculated for each of the 3 periods.
1.3.3. Behavioral coding
Videotapes obtained for this purpose were coded
for behavioral state during the resting baseline
period, the event, and the recovery period. Beha-
vioral state was assessed using a modified version
of a coding system designed for premature infants
(Als et al., 1988). This scheme was used to categorize each infant’s state on a scale of 1 to 6:
quiet sleep, active sleep, quiet awakeness/
drowsy, awake and alert, awake and fussy, and
crying. Tapes were coded in 10-second epochs.
Codes recorded represented the highest level of
state or activity noted during each 10-second
epoch. Percent agreement for state codes,
obtained on 20% of the tapes, was 92.9%. Infants’
average state score during the resting baseline,
event and recovery periods were calculated.
1.3.4. Analysis plan
The physical exam and heel-stick blood draw
events were assessed to ensure that they did not
differ between treatment groups. Distributions
were examined and measures found to be positively skewed were log transformed. Next, dependent measures were examined to determine if
they were affected by treatment group, event, or
trial.
1032
Cortisol data were log transformed to normalize
the distribution. Cortisol measures were examined
to determine whether cortisol levels were affected by treatment group (No treatment, Treatment), event (Heel-stick, Physical exam), or trial
(Resting baseline, 20 min post event, and 40 min
post event) using a ANOVA with repeated measures on the last 2 factors, with Greenhouse-Geisser corrections as necessary. Planned contrasts to
examine linear and quadratic effects were utilized
to test the hypothesis that infants with antenatal
betamethasone would not increase cortisol to
either event, but that infants without antenatal
betamethasone would respond to the heel-stick
blood draw.
Next, infants’ heart rate and behavioral state
scores were examined to determine whether they
were affected by treatment group (No treatment,
Treatment), event (Heel-stick, Physical exam), or
trial (Resting Baseline, Event, and Recovery) using
separate ANOVAs with repeated measures on the
last 2 factors, with Greenhouse-Geisser corrections as necessary. The hypothesis that heart rate
and behavioral state would be higher during the
event relative to baseline and recovery was tested
utilizing planned contrasts to test for quadratic
trends.
2. Results
2.1. Assessment of heel-stick and physical
exam
Duration of the heel-stick and physical exam
events did not differ between infants with or
without antenatal betamethasone; heel-stick (M =
3.6 minutes vs. M = 3.8 minutes), t(16) = 1.88, p =
0.08, physical exam (M = 3.8 minutes vs. M = 3.7
minutes), t(16) = 0.23, p = 0.82. Likewise, the
groups did not differ on number of previous heelsticks (M = 7.2 vs. M = 7.5), t(15) = 0.23, p = 0.52,
or physical exams (M = 4.4 vs. M = 5.2), t(16) =
1.84, p = 0.09. Additionally, to ensure that the
inclusion of twins did not alter the pattern of
results the mean cortisol levels at baseline,
response and recovery on the physical exam and
heel-stick event days in twins and non-twins were
examined and found not to differ (p’s > 0.20).
E.P. Davis et al.
main effect of trial, F(2,15) = 6.4, p = 0.01, but
not treatment group, F(1,15) = 2.3, p = 0.38, or
event, F(1,15) = 0.28, p = 0.71. There was, however, a significant three-way interaction between
treatment group, event, and trial, F(2,15) = 5.38,
p = 0.017. This finding remained when the two
subjects with missing sample 3 data were excluded F(2,13) = 8.2, p = 0.002.
To explore the 3-way interaction, separate
treatment 2 (group) by 2 (trial) ANOVAs with
repeated measures on the last factor were run for
each event. For the physical exam there was a
main effect of trial, F(2,15) = 5.26, p = 0.019, but
no interaction between treatment group and trial,
F(2,15) = 1.27, p = 0.20. Planned contrasts for the
main effect of trial revealed a significant linear
trend such that cortisol decreased from resting
level to 20 and 40 mins post exam F(1,16) = 9.6,
p = 0.007 (see Fig. 1).
For the heel-stick blood draw, both the main
effect of trial, F(2,15) = 7.5, p = 0.005, and the
interaction between treatment group and trial,
F(2,15) = 4.03, p = 0.04, were significant. Polynomial contrasts for this interaction yielded significant quadratic trends, F(1,16) = 7.35, p =
0.015. Infants with antenatal betamethasone
treatment displayed decreases in cortisol at 20
and 40 minutes post event relative to their resting
baseline levels, whereas infants in the no treatment group showed increases in cortisol at 20
minutes post event (See Fig. 2).
Betamethasone was administered between one
and twenty-one days prior to delivery. Days post
betamethasone administration was not correlated
with cortisol levels (p’s > 0.1) using Spearman
rank-order correlation. Thus infants treated three
weeks prior to testing exhibited cortisol suppressions that were no different than suppression
2.2. Cortisol
Two subjects were missing sample 3 on the physical exam day due to a failure to collect a sufficient volume of saliva. For the 2 subjects with
missing sample 3 data the mean of their standard
scores for sample 1 and 2 on the physical exam
day was used to estimate sample 3. There was a
Fig. 1. Comparison of salivary cortisol changes in
response to a physical exam in infants with and without
antenatal betamethasone exposure.
Prenatal Corticosteroid Exposure
1033
Fig. 2. Comparison of salivary cortisol changes in response to a heel-stick blood draw in infants with and without
antenatal betamethasone exposure.
exhibited by infants who were treated within one
week of testing.
2.3. Heart rate
Heart rate data were not obtained from one subject on the heel-stick day due to technical problems. There was a main effect of trial, F(2,14) =
24.99, p = 0.0001, but not treatment group,
F(1,15) = 0.062, p = 0.81, or event, F(1,15) =
0.007, p = 0.93. Planned contrasts for quadratic
trends showed that infants display higher heart
rates during the event relative to the resting baseline or recovery period, F(1,15) = 52.2, p =
0.0001. There was also a treatment group by trial
interaction, F(2,14) = 5.65, p = 0.016, indicated
that infants with antenatal betamethasone treatment displayed a significant increase in heart rate
from the baseline to the event period, t(8) = 9.8,
p = 0.0001, whereas the increase in heart rate
seen in infants without treatment did not reach
traditional levels of significance, t(8) = 1.97, p =
0.08 (see Table 2).
2.4. Behavioral state
The main effects of trial, F(2,15) = 21.8, p =
0.0001, and event, F(1,16) = 12.67, p = 0.003, but
not treatment group, F(1,16) = 1.11, p = 0.31, were
significant. Quadratic trends testing the hypothesis that infants would be in a more aroused behavioral state during the event as compared to
resting baseline and recovery were significant,
F(1,16) = 46.13, p = 0.0001. There was also an
event by trial interaction, F(2,15) = 9.58, p =
0.002, indicated that, consistent with the literature on full-term infants, these premature infants
were in a more aroused behavioral state during
the heel-stick event period as compared to the
physical exam event period, t(17) = 6.4, p =
0.0001 (See Table 3).
3. Discussion
Infants exposed to antenatal betamethasone
failed to mount a cortisol response to a painful
stimulus, a heel-stick blood draw. In fact, these
Table 2 Comparison of heart rate changes in response to heel-stick blood draw and physical exam in infants
with and without antenatal betamethasone exposure
No Betamethasone
Heel-stick
Resting baseline
Event
Recovery
Physical Exam
Resting baseline
Event
Recovery
Betamethasone
N
M
SD
N
M
SD
8
8
8
148.3
153.5
147.2
16.6
13.5
12.7
9
9
9
145
163.4
145.7
14.3
18.4
16.8
8
8
8
151.8
158.3
147.9
13.1
14.9
14.6
9
9
9
140.2
158.2
145.4
14.6
14.1
12.5
Heart rate is reported in beats per minute.
1034
E.P. Davis et al.
Table 3 Comparison of behavioral state changes in response to heel-stick blood draw and physical exam in
infants with and without antenatal betamethasone exposure
No Betamethasone
Heel-stick
Resting baseline
Event
Recovery
Physical exam
Resting baseline
Event
Recovery
N
M
9
9
9
9
9
9
Betamethasone
SD
N
M
SD
1.5
3
1.7
0.66
1.12
0.86
9
9
9
1.6
3.3
1.5
0.72
1.29
0.3
1.3
1.9
1.5
0.24
0.57
0.83
9
9
9
1.2
2.4
1.8
0.2
0.62
0.59
Behavioral state is scored on a scale of 1–6 (see text for details).
infants exhibited a significant decrease in cortisol
in response to this event. Notably, infants with
antenatal betamethasone treatment reacted to
the heel-stick with increases in both behavioral
state and heart rate indicating that they were
responding to this event. In contrast, infants who
did not receive prenatal betamethasone treatment displayed an increase in cortisol in response
to the heel-stick stressor. This cortisol response,
also displayed by full term infants, is considered
appropriate and supports adaptation to challenge
(Gunnar, 1992). Consistent with previous research
demonstrating that baseline cortisol is suppressed
only for the first two to seven days after prenatal
treatment, these two groups of infants did not
differ in their resting baseline cortisol levels.
These data suggest that infants with betamethasone treatment are able to maintain appropriate
levels of baseline cortisol but their ability to
mount a cortisol response to stress is impaired
even beyond the first week after treatment.
Similar to healthy full term infants, neither
group of premature infants displayed cortisol
increases in response to a physical exam, which
they had experienced previously (Gunnar et al.,
1992). Infants in this study experienced multiple
exams on a daily basis and may have habituated to
this event. In support of this explanation, infants
displayed smaller behavioral responses to the
physical exam than the heel-stick blood draw.
An inability to secrete cortisol in response to
stress, such as the painful stimulation of a heelstick blood draw, may reflect dysregulation of the
HPA axis (McEwen, 1998). Failure to respond to
stressful events with an increase in cortisol may
have implications for infant functioning. Patients
with cortisol deficiency manifest hypotension,
which is resistant to the effects of volume expansion and vasopressors (Helbock et al., 1993), a
frequent concern in this patient population. A
hypoactive HPA axis is also related to autoimmune
disorders such as rheumatoid arthritis and asthma
(Stratakis and Chrousos, 1995). The ability to
mount a cortisol response is necessary to survive
even moderate challenges. The failure to produce
sufficient cortisol may limit infants’ capacity to
manage challenge. Infants who received antenatal
corticosteroids displayed a greater heart rate
response as compared to infants who did not
receive treatment. This may be an indication that
these infants are less able to regulate stress
responses. Research has demonstrated that a single dose of antenatal betamethasone reduces
mortality among premature infants (Crowley,
1995). These data do not suggest that clinical
administration of corticosteroids is contraindicated. However, this work demonstrates that
just one course of antenatal corticosteroids
affects postnatal regulation of the HPA axis.
There is a population of infants who receive antenatal betamethasone, but are not delivered until
after 34 weeks gestation, when lungs are sufficiently mature. Understanding the effects of antenatal corticosteroids may have implications for
the treatment of these infants.
Researchers have proposed that glucocorticoid
exposure prenatally has a programming effect on
CNS development (Welberg and Seckl, 2001) and
that early experiences that impact the HPA axis
may create vulnerability for the development of
mood and anxiety disorders (Pine and Charney,
2002). The long-term implications of prenatal
exposure to corticosteroids in humans are poorly
understood. These data indicate that prenatal
exposure to corticosteroids impairs HPA axis regulation during the neonatal period. Future research
is needed to explore whether the effects of prenatal corticosteroids persist and alter the developmental trajectory of the HPA axis along with
related cognitive and emotion systems.
Prenatal Corticosteroid Exposure
Acknowledgements
This research was supported by grant from the
Minnesota Medical Foundation (643-7051). The
authors wish to give a very special thank you to
the families who participated in this research and
to the nurses, lab technicians, and physicians at
Fairview University Medical Center and Hennepin
County Medical Center, Minneapolis, MN. Thanks
also to the many undergraduates at the University
of Minnesota that assisted with data collection
and to Andrea Geiben at the University of Trier
for careful analysis of the salivary cortisol data.
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