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Angiogenic Factors and Fluoride
During mid-gestation, the maternal uterine spiral arteries must be transformed into low-resistance, high-capacitance blood vessels that can provide increasing amounts of oxygen and nutrients to the growing fetus. Poor spiral artery remodeling due to an abnormal balance of proangiogenic and antiangiogenic factors causes the hypertension seen in preeclampsia.
The fetus secretes adrenomedullin, a proangiogenic vasodilator, into the placenta. In normal human pregnancies, adrenomedullin is elevated approximately 5-fold in the maternal plasma, but often blunted in pregnancies complicated by preeclampsia.43 Sodium fluoride has been shown to completely block the effect of adrenomedullin in pregnant rats.44
Fetal fluoride levels in blood and amniotic fluid depend on maternal fluoride exposure. The use of fluoride supplements (1.5 mg/day) doubles fetal blood concentrations.7 When pregnant women consume 1.25 mg of fluoride per day, the fluoride concentration in their amniotic fluid is significantly higher than in women who consume 0.25 to 1.0 mg fluoride.45 Fluoride levels in amniotic fluid – which are considerably higher at term than earlier in the third trimester – are positively correlated in a dose-response relationship with fluoride content and pathology of fetal bones, with significantly greater fluoride levels in fetuses born to mothers who have dental fluorosis.46,47
Soluble endoglin (sEng) is an antiangiogenic protein whose concentrations are elevated in serum and in amniotic fluid of women with preeclampsia.48 Tskitishvili et al. found that amniotic tissue cultures treated with sodium fluoride show significantly higher expression levels of sEng, at any dose and time-point tested.49
Inflammation: Periodontal Disease, Preeclampsia, and Dental Fluorosis
Maternal periodontal disease with systemic inflammation as measured by hs-CRP (high-sensitivity C-reactive protein) is increased in preeclampsia and represents a marker of its severity.50,51 Women with a history of periodontal treatment are more likely to develop severe preeclampsia than women without a prior history of treatment.52 Periodontal treatment exposes women to extremely high concentrations of topical fluoride (22,600 ppm), some of which is absorbed into the bloodstream and placenta.
Plasma levels of hs-CRP are significantly higher among patients with fluorosis compared with controls.53 A clinical study found a strong association of occurrence of periodontal disease in people who had dental fluorosis. As the severity of fluorosis increased, periodontitis increased from 8.5% to 35.8%. Also, periodontitis was significantly more common in females.54 Many studies and published documents have shown that increased fluoride exposure is directly linked to increased periodontal disease.55
Preeclamptic women with periodontal disease are at greater risk for preterm delivery.56 Maternal fluoride consumption is also a risk factor for preterm birth, a leading cause of long-term neurological disabilities in children. The societal economic burden associated with preterm birth is more than $25 billion per year in the US.57 Preeclampsia is the underlying cause of about 25% of all medically indicated preterm deliveries.
Another pro-inflammatory factor in preeclampsia is elevated liver enzymes, which are significantly higher in early-onset preeclampsia.58 Elevated liver enzymes have been found in children, based on the levels of fluoride in drinking water (in a dose-response manner) and on their degree of dental fluorosis.59
Fluoridated Water, Dental Fluorosis, and Preeclampsia
A case-control study found a significant association between fluoride levels in drinking water, dental fluorosis in mothers, and low birth weight of newborns. Preeclampsia was significantly associated with low birth weight (23.1% in cases vs. 11.6% in controls).60
Systemic exposure to fluoride through drinking water is associated with an increased risk of dental and bone fluorosis in a dose-response manner – without a detectable threshold.61 British researchers estimate the prevalence of dental fluorosis of all levels of severity to be 15% in nonfluoridated areas and 48% in fluoridated areas.62
From 1987 to 2004 in the US, the prevalence of moderate and severe dental fluorosis nearly tripled from 1.3% to 3.6%.63 There was also a 13.5% increase in the percentage of Americans receiving public water that was fluoridated (from 60.5% to 68.7%).64
During the same 18 years in the US, the incidence rate of preeclampsia rose by 25%: from 23.6 to 29.4 cases per 1000 deliveries.65 Rates of severe preeclampsia are steadily increasing. In the largest US cohort study (120 million births), the prevalence rate for severe preeclampsia nearly quintupled from 0.3% in 1980 to 1.4% in 2010.26
The limited available population data reveal that, from 1996 to 2004 the preeclampsia rate averaged 19% higher in the two most fluoridated regions of the US (South and Northeast), than in the two least fluoridated regions (Midwest and West): 31.7 vs. 26.6 cases per 1000 deliveries. The preeclampsia rate averaged 40% higher in the South than in the West: 34.1 vs. 24.3 cases per 1000 deliveries.65 In 2004, the average fluoridation rate in the South's 16 states was 81%, compared with 46% in the West's 13 states.
Note: The age-adjusted death rate in 2010 for essential hypertension and hypertensive renal disease was 9% higher in the 22 states fluoridated at 80% or more (average 92%) than in the 27 states fluoridated at less than 80% (average 56%).66
Fluoridated Water, Hypothyroidism, and Preeclampsia
In 2015, a major population-level study analyzed data from 99% of England's 8020 general medical practices. It found a positive association between fluoride levels in water and patients diagnosed with hypothyroidism. High hypothyroidism prevalence was 30% more likely in practices located in areas with fluoride levels in excess of 0.3 mg/l. Those located in the West Midlands (a wholly fluoridated area) were nearly twice as likely to report high hypothyroidism prevalence in comparison with Greater Manchester (nonfluoridated area).67 The study did not include undiagnosed subclinical hypothyroidism, which is associated with many health problems, including preeclampsia and ADHD.
Preeclampsia is often complicated with subclinical hypothyroidism. Many studies have shown a relation between the level of thyroid hormones and development and severity of preeclampsia.68 In an analysis of pregnancy outcomes in 24,883 women, after adjusting for confounding factors, there was a significant association between subclinical hypothyroidism and severe preeclampsia.69 A 2013 retrospective cohort study of 223,512 pregnancies found that primary hypothyroidism was associated with increased odds of preeclampsia (OR = 1.47).70
Singh et al. tested drinking water and body fluids for fluoride content, plus thyroid hormone and TSH levels, in children with dental fluorosis. They observed that high fluoride exposure can cause functional abnormalities of the thyroid. "Different degrees of dental fluorosis could be observed, with significant deviation in the serum thyroid hormone levels."71 Note: ER stress has been detected in the thyroid glands of fetuses whose mothers had dental fluorosis.17
Hypothyroidism is associated with ADHD and is considered a potential cause of the disorder. Also published in 2015 was the first population-based study to examine the relationship between exposure to fluoridated water and ADHD prevalence. A multivariate regression analysis showed that artificial water fluoridation prevalence was significantly positively associated with ADHD prevalence. After socioeconomic status was controlled, each 1% increase in artificial fluoridation prevalence in 1992 was associated with approximately 67,000 to 131,000 additional ADHD diagnoses from 2003 to 2011 in the US.72
FDA: Fluoride and Pregnancy
The FDA classifies fluoride as an unapproved drug in Pregnancy Category C: "Animal reproduction studies have shown an adverse effect on the fetus, and there are no adequate and well-controlled studies in humans." The FDA says that a drug in category C "may pose risks similar to a drug in Category X," which carries the warning: "The risks involved in use of the drug in pregnant women clearly outweigh potential benefits."73
As for any potential benefits of swallowing fluoride, after reviewing the best available evidence for the effectiveness of water fluoridation, the FDA would only allow a weak claim: "Drinking fluoridated water may reduce the risk of tooth decay" – a far cry from the inflated sales pitch of fluoridation promoters.74,75
Since 1966, the FDA has prohibited claims that prenatal fluoride supplements benefit the teeth of children.76
Fluoride is added to the drinking water of more than 200 million Americans. This EPA-regulated water contaminant now pervades the nation's processed-food-and-beverage-chain, essentially making the US artificially fluoride endemic.
The actual amount of fluoride that pregnant women typically consume per day is unknown.
To begin with, measure fluoride levels in routine blood and urine tests. For women who previously experienced preeclampsia, determine if their drinking water was fluoridated. Did they regularly drink tea or beverages manufactured with fluoridated water? How severe was their preeclampsia? Do they have dental fluorosis, a biomarker of their genetic susceptibility to fluoride?
A next step is to compare the concentration of fluoride in preeclamptic placentas with the severity of preeclampsia, as well as with placentas from normal pregnancies.
Preeclampsia used to be called "toxemia," until 20th-century science failed to identify the causative substance. The current name preeclampsia (preconvulsions) continues to reflect our failure to determine the etiology of this life-threatening disease of the placenta. This century's science suggests that "placental fluorosis" may be a far more accurate term.
Bottom line: Not ingesting fluoride poses absolutely no risk (or lack of benefit) to the placenta or fetus; however, consumption of fluoride may very well increase a woman's risk of preeclampsia and its dangerous short-term and lifelong consequences for her and her child.
Women who are pregnant (or intend to be) should not swallow fluoride in supplements, in dental products, or during dental procedures. They should not consume fluoridated water or beverages manufactured with it.
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