Bull Vet Inst Pulawy 48, 449-452, 2004

EFFECT OF MATERNAL ADMINISTRATION

OF DEXAMETHASONE DURING LAST WEEKS
OF PREGNANCY ON FOETAL SKELETAL SYSTEM IN PIGS
EWA LIWA, SYLWESTER KOWALIK, MARCIN R. TATARA
AND TADEUSZ STUDZISKI
Department of Animal Physiology, Faculty of Veterinary Medicine,
Agricultural University of Lublin, 20033 Lublin, Poland
e-mail: ewaRST@interia.pl
Received for publication July 13, 2004.

Abstract
The influence of dexamethasone, given during the last
three weeks of pregnancy to sows, on mineral density, and
geometrical, mechanical and morphometrical parameters of the
femur and humerus of their offspring was evaluated.
Dexamethasone was given i.m in the dose of 3 mg per sow every
second day, and at the same time sows from control group were
administered in the same manner physiological saline in the dose
of 1.5 ml per sow. The newborn not suckling piglets from
experimental and control sows were sacrificed in the first hour
after birth and femora and humeri were separated and frozen at
25oC until further analyses. Using dual-energy x-ray
absorptiometry (DEXA) method, bone mineral density (BMD)
and bone mineral content (BMC) were estimated.. The obtained
results indicate that the administration of dexamethasone
decreased BMD, BMC, and the geometrical and mechanical
properties of the bones. This model of maternal administration
of dexamethasone directed to evoke skeletal effects during
prenatal life may be useful in further elucidation of
glucocorticoids on bone formation in prenatal life.

Key words: newborn piglets, prenatal life,

dexamethasone, bones.
The mechanism of glucocorticoids actions
during the prenatal life is poorly understood. They
modify the expression of some transcription factors
required for normal organogenesis by upregulating or
downregulating them (1). Growth retardation and bone
mass decreased are common complications of corticoid
therapy (11). Glucocorticoids are often used as
antiinflammatory and immunosuppressive drugs despite
their negative effects on bone growth and calcium (Ca)
balance, leading to a severe osteopenia or osteoporosis
(12). Glucocorticoids have an important role in foetal
development, especially in the maturation of foetal
tissues and during neonatal and postnatal life (2).
Dexamethasone is devoid of mineralocorticoid activity
and effectively crosses the placenta. Prenatal
administration of steroids improves lung hypoplasia and

normalizes lung morphology while inducing structural

maturity what decreases mortality in preterm human
infants (3). However, foetal exposure to excess of
glucocorticoids has been implicated as a causative factor
in foetal growth retardation and glucose intolerance in
adult life (1, 3, 8). The benefits of prenatal
corticosteroids treatment for accelerating lung
maturation are well seen in human foetuses expected to
be born prematurely (3). The mechanisms of the action
of prenatal dexamethasone therapy on foetal organs
including skeletal system are still limited and it demands
further experimental and clinical investigations. The aim
of this study was to determine an effect of prenatal
administration of dexamethasone for 3 weeks before
birth on the development of the skeletal system in
newborn piglets.

Material and Methods

Experimental
design
and
sampling
procedure. The experiment was carried out on 6
pregnant sows and 24 their newborns of Large Polish
White breed. The sows were housed under standard
rearing conditions (temperature and humidity) with
constant access to fresh water and fed standard
commercial diets for pregnant sows. Sows were fed at
7.00 a.m. and 3.00 p.m. Starting from day 24 before
delivery, 3 pregnant sows were administered i.m.
dexamethasone in the dose of 3 mg per sow every
second day (Dex group), wheras 3 other sows were
given in the same manner physiological saline in the
dose of 1.5 ml per sow (PhS control group). The
newborns were divided consequently into the
experimental (Dex) and control (PhS) groups. Every
piglets group consisted of 12 animals. The weight of
the individual newborns was measured just after their
birth. In the first hour after the birth the animals from
both groups were killed with lethal doses of
pentobarbitalum natrium given intravenously (Morbital;

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Biowet Puawy, Poland) and their left and right femora

and humeri were separated. The bones were stored at
25oC until further analyses were performed. During the
tests, they were at room temperature about 20oC.
Analysis of the geometrical and mechanical
parameters. The geometrical parameters such as cross
sectional area (A), second moment of inertia (Ix) and mean
relative wall thickness (MRWT) were investigated through
the measurement of the horizontal and the vertical diameter
in the middle of the length of the femur and humerus (4, 5,
6, 7). The mechanical properties of the investigated bones
were estimated using three-point bending test in INSTRON
4302 apparatus connected with a computer, registering
relationship between force acting perpendicularly to the
longitudinal bone axis and resulting in displacement (4, 5).
The results of the mechanical analysis were presented
graphically and the maximum elastic strength (Wy) was
estimated.
Bone mineral density. Bone mineral density
(BMD) and bone mineral content (BMC) were measured
with dual-energy x-ray absorptiometry (DEXA) method
and NORLAND XR 43 apparatus. Bone density was
measured for proximal and distal ends that include both
the trabecular and the cortical bone compartments and
for the whole bone as well.
Analysis of the bone morphometry. The bone
morphometrical parameter such as weight/length index
(WLI) was determined by the measurement of the total
weight and length of the femur and calculated by
following equations WLI = weight/length.
Statistical analysis. All data are presented as a
mean standard error (S.E.). Statistical analyses were
performed using STATISTICA 5.0 software. The
Students t-test was used to determine statistical
significance level of differences between the
investigated groups. The level of statistic significance
was set at P0.05 for all comparisons.

Results
The mean body weight of newborns was higher
in the experimental group (1716 g 98) than that in
control one (1324 g 82; P=0.01). The femur and
humerus were longer in Dex newborns, as compared to
controls (PhS) and this difference was statistically
significant (P<0.004 and P<0.006) (Tables 1 and 2). The
weight of both bones increased in Dex newborns and
statistically significant differences were stated for the
femur (P<0.02). The WLI reached higher value in Dex
group than in control one although the differences were
not statistically significant (P=0.33 and P=0.07,
respectively) (Tables 1 and 2). The geometrical
parameters of the femur and humerus, including the cross
sectional area and the second moment of inertia were
significantly higher in the newborns from the experimental
group than in the control group (Tables 1 and 2). The
MRWT of the humerus was higher in the control group
than in the experimental whereas the opposite result was
stated in the femur, but the differences were not statistically
significant (P=0.59 and P=0.09, respectively) (Tables 1 and

2). The dexamethasone administration lowered the mean

values of the maximum ultimate strength of both bones in
comparison to the control group (Tables 1 and 2). The
BMD and BMC obtained from both evaluated parts of
bones (proximal and distal) and from the whole femur and
humerus were lower in Dex newborns (Tables 1 and 2).

Discussion
The clinical investigation indicates that
glucocorticoids including dexamethasone inhibit body
growth and induce bone mass reduction when given during
postnatal life (1, 6, 7, 8). However, current practice
recommendations order the administration of either
intramuscular betamethasone or dexamethasone to women
at risk for preterm delivery (3). Dexamethasone crosses
effectively the placenta and improves lung hypoplasia.
Glucocorticoids influence the metabolism of the whole
organism and increase the level of glucose in serum and
protein catabolism (9). Glucose is the main source of
energy for the growing foetus during pregnancy and it is
commonly known that mothers with high level of glucose
can deliver infants with very high body weight. And it is
still unknown what is the influence of the prenatal
administration of glucocorticoids on the skeletal
development not only in animal but also in humans. The
growing pig is used as a model for growing children (9).
Steroids are used more and more. Inhalated corticosteroids
are now accepted as first-line of preventive antiinflammatory therapy for asthma. The data from
experiments proved that the number of genes is regulated
by glucocorticoids directly or indirectly through interaction
with other transcription factors (11, 12). The presented
study indicates that the administration of low dose of
steroids to pregnant sows markedly influenced bone
mechanical and geometrical properties, mineral density and
mineral content in foetus as it was demonstrated just after
the first hour of life of piglets. The prenatal administration
of dexamethasone increased the length and the weight of
the humerus and femur but lowered all the mechanical and
geometrical parameters of the bones. Further studies are
needed for more thorough understanding of the action of
exogenous steroids administered during pregnancy.
Presumably, they act through the suppression of the
pituitary-adrenal axis activity not only in mother but in
foetus as well. The prenatal administration highly
beneficial when there are prenatal complications, but it has
adverse effects on the processes of mineralization of the
skeletal system at that time and this effect remains during
neonatal and postnatal life in animals and humans, and
influences the peak bone mass reached in adults. The rate
of bone loss after menopausal time depends on the peak
bone mass reached during prenatal time (3, 10).

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Table 1
Characteristics of femur properties in newborn piglets born by sows treated (Dex) and not treated (PhS) with dexamethasone

Group

PhS

Dex

24

24

Length (cm)

5.19 (0.08)

5.76 (0.14)*

Weight (g)

7.65 (0.36)

9.56 (0.75)

Cross-sectional area (mm2)

33.55 (1.94)

21.5 (0.56)*

Second moment of inertia (mm4)

131.2 (12.5)

45.0 (2.13)*

Mean relative wall thickness of femur

0.83 (0.03)

1.00 (0.08)

Weight/length index

1.46 (0.06)

1.62 (0.16)

Maximum elastic strength (N)

338.0 (32.3)

270.0 (18.7)

BMD of proximal part (g/cm2)

0.184 (0.004)

0.170 (0.002)*

BMD of distal part (g/cm2)

0.205 (0.005)

0.180 (0.004)*

BMD of the whole bone (g/cm2)

0.219 (0.006)

0.187 (0.002)*

BMC of the whole bone ()]

0.397 (0.03)

0.275 (0.01)

Number of bones investigated

Statistically significant differences between PhS and Dex groups are marked * for P-value 0.05

Table 2
Characteristics of humerus properties in newborn piglets born by sows treated (Dex) and not treated (PhS) with dexamethasone

Group

PhS

Dex

24

24

Length (cm)

5.06 (0.08)

5.8 (0.18)*

Weight (g)

6.75 (0.41)

9.06 (0.79)*

Cross-sectional area (mm2)

31.3 (1.18)

18.5 (0.51)*

Second moment of inertia (mm4)

139.1 (8.12)

45.8 (2.03)*

Mean relative wall thickness

1.00 (0.07)

0.96 (0.04)

Weight/length index

1.32 (0.06)

1.54 (0.09)

Maximum elastic strength (N)

355.18 (25.6)

131.6 (7.8)*

BMD of proximal part (g/cm2)

0.196 (0.004)

0.153 (0.005)*

BMD of distal part (g/cm2)

0.184 (0.006)

0.157 (0.003)*

BMD of the whole bone (g/cm2)

0.216 (0.006)

0.167 (0.002)*

BMC of the whole bone (g)

0.334 (0.03)

0.275 (0.008)

Number of bones investigated

Statistically significant differences between Dex and PhS groups are marked * for P-value 0.05

452

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