Fluoride Metabolism in Pregnant Women: A Narrative Review of the Literature

Abstract

Epidemiological studies use biomarkers of fluoride exposure in pregnant women as surrogate measures of fetal fluoride exposure; however, there is little understanding of how pregnancy affects fluoride metabolism and its biomarkers. This narrative review summarizes the changes of pregnancy that have the potential to impact fluoride's absorption, distribution and excretion, and highlights the limited body of evidence on the topic. The physiologic systems that experience pregnancy-associated changes relevant to fluoride's metabolism are the cardiovascular, renal, metabolic and gastrointestinal, as well bone and calcium metabolism and the body's acid-base balance. The available evidence indicates that fluoride is found in the maternal plasma and urine, placenta, amniotic fluid and fetus. Although plasma and urinary fluoride vary across gestation, there is insufficient quality evidence to determine the direction or extent of such variation. Furthermore, there is no doubt that fluoride from maternal blood crosses the placenta and is absorbed and excreted by the fetus; however, the biological mechanisms behind this placental passage are unknown. Research on maternal and prenatal biomarkers of fluoride exposure would benefit from studies on how pregnancy-associated changes affect the metabolism of fluoride across gestation, the mechanisms for the intestinal absorption of fluoride in pregnant women, and the placental passage of fluoride.

Keywords: fluoride; fluoride metabolism; fluoride pharmacokinetics; maternal-fetal fluoride exchange; pregnancy; pregnant.

Figure 1

Summary of the physiological changes of pregnancy with potential to affect fluoride metabolism.

Figure 2

Hypothesis for the placental transfer of fluoride. Nonionized fluoride (HF, pKa = 3.4) diffuses passively through lipid bilayers and moves towards the most alkaline compartment. Under normal conditions, fluoride (F⁻) will remain slightly more concentrated in maternal blood due to the slightly more alkaline environment. However, any transient disturbance in the maternal or fetal blood pH has the potential to alter the direction of the movement of F⁻.