Folic Acid

Folic Acid and Miscarriage

Low folate status associated with 47% higher risk of miscarriage, may cause abnormal karyotype

Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL, women with low (< or =2.19 ng/mL) folate levels were at increased risk of miscarriage  (adjusted odds ratio, 1.47), whereas women with higher folate levels (3.96-6.16 ng/mL and > or =6.17 ng/mL) showed no increased risk of miscarriage (odds ratio, 0.84 and odds ratio, 0.74, respectively). Low folate levels were associated with a significantly increased risk of miscarriage when the fetal karyotype was abnormal (odds ratio, 1.95) but not when the fetal karyotype was normal (odds ratio, 1.11) or unknown (odds ratio, 1.45).

Having both low folate and vitamin B6 increases the risk of miscarriage four-fold

Homocysteine, folate, and vitamins B(6) and B(12) concentrations were measured in plasma obtained before conception. Mean vitamin B(6) concentration was lower in patients than in controls (34.0 versus 37.9 nmol/L). In addition, the risk of miscarriage tended to increase with decreasing plasma vitamin B(6) and folate concentration, although the significance of these trends was further reduced in logistic models that included age, body mass index, and both vitamins. The risk of miscarriage was four-fold higher among women with suboptimal plasma concentrations of both folate and vitamin B(6) (folate less than or equal to 8.4 nmol/L and vitamin B(6) less than or equal to 49 nmol/L) than in those with higher plasma concentrations of both vitamins (odds ratio 4.1). Homocysteine and vitamin B(12) status were not associated with miscarriage risk.

Also see:
Vitamin B6 and Miscarriage

Low dietary folate associated with miscarriage, developmental delay and birth defects

MTHFR +/+ and +/- female mice were fed a control or folic acid-deficient diet for 6 weeks, then mated with MTHFR +/- males. RESULTS: Maternal MTHFR and folate deficiencies resulted in increased developmental delays and smaller embryos. We also observed a low frequency of a variety of embryonic defects in the experimental groups, such as neural tube, heart looping, and turning defects; these results mimic the low incidence and multifactorial nature of these anomalies in humans. Folate-deficient mice also had increased embryonic losses and severe placental defects, including placental abruption and disturbed patterning of placental layers. CONCLUSIONS: Our study provides biological evidence linking maternal MTHFR and dietary folate deficiencies to adverse pregnancy outcomes in mice. It underscores the importance of folate not only in reducing the incidence of early embryonic defects, but also in the prevention of developmental delays and placental abnormalities that may increase susceptibility to other defects and to reproductive complications.

Excess dietary folic acid is associated with delayed embryonic development and birth defects

MTHFR +/+ or +/- pregnant mice on a control diet or folic acid-supplemented diet (20-fold higher than the recommended intake) were examined for embryonic loss, delay, and defects. RESULTS: Plasma homocysteine levels were not affected by diet. The folic acid diet was associated with embryonic delay and growth retardation, and may confer susceptibility to embryonic defects. The folic acid diet did not adversely affect placental development. Embryos from the folic acid diet MTHFR +/+ group were delayed and the folic acid diet was associated with thinner ventricular walls in embryonic hearts. There was a significant interaction between maternal MTHFR deficiency and a high folate diet for several developmental outcomes. CONCLUSIONS: Our study suggests that high folate intake may have adverse effects on fetal mouse development and that maternal MTHFR deficiency may improve or rescue some of the adverse outcomes. These findings underscore the need for additional studies on the potential negative impact of high folate intake during pregnancy.

Low folate not associated with recurrent miscarriage

In this Swedish population-based case-control study, we investigated the association between sociodemographic and anthropometric factors, obstetric history and life-style factors, with respect to the risks of first-trimester repeated miscarriage. Low plasma folate levels were not associated with increased risks.

Dietary folate may improve fetal blood flow

The angiogenic to antiangiogenic ratio was positively related to intake of vitamin D, vitamin B(2), B(12), dietary folate equivalents, iron, and zinc and negatively related to transfats.

Folic Acid and Birth Defects

Folate before conception may reduce Down Syndrome odds

There is evidence that some mothers of infants with Down's syndrome have abnormal metabolism of folate and methyl, as well as mutations in folate genes, which are features that are also seen in neural-tube defects (NTD). In the families at risk of NTD, there were a total of 11 pregnancies affected by Down's syndrome in 1492 at-risk pregnancies (compared with 1·87 expected on the basis of maternal age), which was a significant increase. In the families at risk of Down's syndrome, there were seven NTD pregnancies in 1847 at risk, compared with 1·37 expected. In this study, we provide direct evidence of a link between Down's syndrome and NTD. Folate supplementation before conception has the potential to reduce the frequency of Down's syndrome.

Also see:
Birth Defects

Excess folic acid supplementation can lead to reductions in fetal body weight and length

Four groups of Wistar rats were classified on the basis of physiological status (virgin v. pregnant) and the experimental diet administered (folic-acid-supplemented, 40 mg/kg diet v. control, 2 mg folic acid/kg diet)(equivalent to 2176 mg for a 120lb woman). Animals were fed on the diets for 3 weeks. Results showed that gestation outcome was adequate in both groups regardless of the dietary supplementation. However, there were reductions in body weight and vertex-coccyx length in fetuses from supplemented dams v. control animals.

Minor deficiency in folate leads to offspring with features of metabolic syndrome

We report on the effects of restricting the supply of specific B vitamins (i.e., B(12) and folate) and methionine, within normal physiological ranges, from the periconceptional diet of mature female sheep. We observed no effects on pregnancy establishment or birth weight, but this modest early dietary intervention led to adult offspring that were both heavier and fatter, elicited altered immune responses to antigenic challenge, were insulin-resistant, and had elevated blood pressure-effects that were most obvious in males.

Folate and BMI

Obesity lowers folate status, despite similar intake; weight loss increases folate staus

At the beginning of the study, the obese women (BMI>or=30 kg/m(2)) were at greater risk of showing serum folic acid concentrations of <14.9 nmol/L, even though there were no differences in folate intake between them and the women with a lower BMI. Among those who lost the most weight (>2.5 kg), the chances of having an increased serum folate concentration were higher, although no significant differences were seen in folate intake with respect to women who lost less weight.

Also see:
Weight and Miscarriage

Folate and Homocysteine

Folate and riboflavin lower homocysteine

Folate and riboflavin, but not vitamin B-6 and cobalamin (vitamin b12), were inversely related to serum total homocysteine after adjustment for confounders.

Also see:
Homocysteine and Miscarriage

Other topics covered under Vitamins:

Biotin, Calcium, Choline, Chromium, Folic Acid, Magnesium, Multivitamins, Phosphorus, Selenium, Vitamin A, Vitamin B12, Vitamin B6, Vitamin C, Vitamin D, Vitamin E, Vitamin K, Zinc