Binge alcohol exposure during all three trimesters alters bone strength and growth in fetal sheep

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Women who drink while pregnant are at a high risk of giving birth to children with neurodevelopmental disorders. Heavy consumption
of alcohol during pregnancy is also known to be deleterious to fetal bone growth in both humans and laboratory animals. However, nothing
is known regarding the effect of maternal moderate and heavy alcohol binging on fetal and maternal bone strength. The purpose of this
study was to determine the effects of moderate and heavy alcohol binging throughout gestation on fetal and maternal bone growth and
strength. The study was conducted using an ovine model system. The large body mass of the ovine fetus, the longer gestation that is more
similar to that of humans, and the fact that all three trimester equivalents occur in utero, make the sheep an excellent model for studying
Fetal Alcohol Spectrum Disorder. Suffolk ewes were mated and, beginning on gestational day 4, received intravenous infusions over 1 h on
3 consecutive days per week followed by 4 days without treatment concluding on day 132 of pregnancy. Pregnant ewes were divided into
four groups: two alcohol treatment groups (0.75 and 1.75 g/kg of body weight), one pair-fed saline control group, and an untreated normal
control group. The fetuses were harvested on gestational day 133. Maternal and fetal femoral and tibial dimensions were measured and the
maximum strength (MPa) carried by the bone tissue was determined using a three-point bending procedure. Maternal bones were not different
among groups. The higher alcohol dose resulted in reduced fetal femoral bone strength, whereas the tibial bone strength was lower
when compared with the normal control subjects. In contrast, the lower alcohol dose increased fetal femoral strength compared to the normal
control subjects. The alcohol-exposed fetal bones also tended to exhibit reduced lengths. We conclude that binge alcohol exposure
throughout gestation resulted in dose-dependent differences in the maximum stress absorbed by the fetal bones. 2006 Elsevier Inc.
All rights reserved.

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Binge alcohol exposure during all three trimesters alters
bone strength and growth in fetal sheep
Jayanth Ramadossa, Harry A. Hoganb, Jon C. Givena, James R. Westc, Timothy A. Cudda,*
aDepartment of Veterinary Physiology and Pharmacology and Michael E. DeBakey Institute, Highway 60, Building VMA, Room 332,
College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4466, USA
bDepartment of Mechanical Engineering, Texas A&M University, College Station, TX 77843, USA
cDepartment of Neuroscience and Experimental Therapeutics, Texas A&M University System Health Science Center, College Station, TX 77843, USA
Received 12 January 2006; received in revised form 6 June 2006; accepted 6 June 2006
Abstract
Women who drink while pregnant are at a high risk of giving birth to children with neurodevelopmental disorders. Heavy consumption
of alcohol during pregnancy is also known to be deleterious to fetal bone growth in both humans and laboratory animals. However, nothing
is known regarding the effect of maternal moderate and heavy alcohol binging on fetal and maternal bone strength. The purpose of this
study was to determine the effects of moderate and heavy alcohol binging throughout gestation on fetal and maternal bone growth and
strength. The study was conducted using an ovine model system. The large body mass of the ovine fetus, the longer gestation that is more
similar to that of humans, and the fact that all three trimester equivalents occur in utero, make the sheep an excellent model for studying
Fetal Alcohol Spectrum Disorder. Suffolk ewes were mated and, beginning on gestational day 4, received intravenous infusions over 1 h on
3 consecutive days per week followed by 4 days without treatment concluding on day 132 of pregnancy. Pregnant ewes were divided into
four groups: two alcohol treatment groups (0.75 and 1.75 g/kg of body weight), one pair-fed saline control group, and an untreated normal
control group. The fetuses were harvested on gestational day 133. Maternal and fetal femoral and tibial dimensions were measured and the
maximum strength (MPa) carried by the bone tissue was determined using a three-point bending procedure. Maternal bones were not different
among groups. The higher alcohol dose resulted in reduced fetal femoral bone strength, whereas the tibial bone strength was lower
when compared with the normal control subjects. In contrast, the lower alcohol dose increased fetal femoral strength compared to the normal
control subjects. The alcohol-exposed fetal bones also tended to exhibit reduced lengths. We conclude that binge alcohol exposure
throughout gestation resulted in dose-dependent differences in the maximum stress absorbed by the fetal bones. 2006 Elsevier Inc.
All rights reserved.
Keywords: Alcohol; Fetal alcohol syndrome; Bone strength; Growth
1. Introduction
Alcohol abuse during pregnancy can result in a variety
of deleterious effects on the developing fetus including Fetal
Alcohol Syndrome (FAS) (Jones et al., 1973). Despite
significant efforts in educating women not to drink during
pregnancy, the incidence of fetal alcohol effects has not decreased,
making alcohol abuse during pregnancy an important
health issue for women as well as for the unborn child
(Institute of Medicine, 1996; Maternal and Child Health
(MCH) Data report, 2003).
A cardinal feature of FAS is growth deficiency (Sokol &
Clarren, 1989). Chronic heavy drinking during pregnancy is
known to be deleterious to fetal bone development in both
humans and laboratory animals. Growth deficits in children
through 14 years of age have been associated with prenatal
exposure to alcohol (Day et al., 2002). Chronic heavy
drinking retards fetal skeletal development (Keiver et al.,
1996; Lee & Leichter, 1983) and reduces ossification of fetal
bones (Keiver et al., 1996) in rats. Even, moderate levels
of developmental alcohol exposure have site-specific effects
on the fetal skeleton (Simpson et al., 2005).
Although previous studies have investigated the effects
of developmental alcohol exposure on fetal skeletal ossification,
no study has examined the effects of maternal alcohol
binging on functional bone measurements. To date,
there has been no study to compare the effects of moderate
and heavy alcohol consumption on fetal and maternal bone
strength. Largely for practical reasons, rats have been the
most commonly used model to study the effects of prenatal
* Corresponding author. Tel.: þ1-979-220-3442; fax: þ1-979-845-
6544.
E-mail address: tcudd@cvm.tamu.edu (T.A. Cudd).
0741-8329/06/$ e see front matter 2006 Elsevier Inc. All rights reserved.
doi: 10.1016/j.alcohol.2006.06.004
Alcohol 38 (2006) 185e192

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