The role of acidemia in maternal binge alcohol-induced alterations in fetal bone functional properties

Abstract

Background: Heavy alcohol consumption during pregnancy negatively impacts the physical growth of the fetus. Although the deleterious effects of alcohol exposure during late gestation on fetal brain development are well documented, little is known about the effect on fetal bone mechanical properties or the underlying mechanisms. The purpose of this study was to investigate the effects of late gestational chronic binge alcohol consumption and alcohol-induced acidemia, a critical regulator of bone health, on functional properties of the fetal skeletal system.

Methods: Suffolk ewes were mated and received intravenous infusions of saline or alcohol (1.75 g/kg) over 1 hour on 3 consecutive days per week followed by 4 days without treatment beginning on gestational day (GD) 109 and concluding on GD 132 (term = 147 days). The acidemia group was exposed to increased inspired fractional concentrations of CO2 to closely mimic the alcohol-induced decreases in maternal arterial pH seen in the alcohol group.

Results: Fetal femurs and tibias from the alcohol and acidemia groups were ~3 to 7% shorter in length compared with the control groups (p < 0.05). Three-point bending procedure demonstrated that fetal femoral ultimate strength (MPa) for the alcohol group was decreased (p < 0.05) by ~24 and 29%, while the acidemia group exhibited a similar decrease (p < 0.05) of ~32 and 37% compared with the normal control and saline control groups, respectively. Bone extrinsic and intrinsic mechanical properties including maximum breaking force (N) and normalized breaking force (N/kg) of fetal bones from the alcohol and acidemia groups were significantly decreased (p < 0.05) compared with both control groups.

Conclusions: We conclude that late gestational chronic binge alcohol exposure reduces growth and impairs functional properties of the fetal skeletal system and that the repeated episodes of alcohol-induced maternal acidemia may be at least partially responsible for these effects.

Keywords: Acidemia; Bone Strength; Fetal Alcohol Spectrum Disorder; Pregnancy; Teratogenicity.

Figure 1. Illustration of the ventilation chamber

Maternal blood gases in the acidemia group were manipulated by placing the ewe in a chamber and manipulating the inspired gases to mimic the change in maternal arterial pH produced by alcohol. The front half of the subject was confined inside the plexiglass chamber, while the rear half was accessible to the investigator for sampling blood. The fractional concentrations of oxygen and carbon dioxide in the chamber were measured using gas monitors.

Figure 2. Binge alcohol and acidemia exposure effects on Fetal Femoral and Tibial Maximum Breaking Force (N)

Fetal femoral and tibial maximum breaking force (N) was significantly reduced in the alcohol and acidemia groups compared to the normal control (*) and saline control (#) groups. Values are means ±SEM.

Figure 3. Binge alcohol and acidemia exposure effects on Fetal Femoral and Tibial Max Breaking Force per Unit Fetal Body Weight (N/kg)

Fetal femoral and tibial maximum breaking force per unit fetal body weight for the alcohol group was significantly lower than the normal control (*) and saline control (#) groups. For the acidemia group, fetal femoral maximum breaking force per unit fetal body weight was significantly lower than the saline control (#) group, and tibial maximum breaking force per unit fetal body weight was significantly lower than the normal control (*) and saline control (#) groups. Values are means ±SEM.

Figure 4. Binge alcohol and acidemia exposure effects on Fetal Femoral and Tibial Ultimate Strength (MPa)

Fetal femoral and tibial bone strength was significantly lower in the alcohol and acidemia group compared to the normal control (*) and saline control (#) groups. Fetal tibial bone strength was significantly different between the normal control and saline control groups. Values are means ±SEM.