THE EFFECTS OF PERICONCEPTIONAL FOLIC-ACID AND VITAMIN SUPPLEMENTATION ON MATERNAL FOLATE LEVELS AND ON NEURULATING HAMSTER EMBRYOS IN-VIVO

We studied the effects of periconceptional oral supplementation of fol ic acid and vitamins on the maternal red blood cell (RBC) folate level of golden hamsters (Mesocricetus auratus, Waterhouse). The effects of folate deficiency and supplementation on the process of neurulation a nd the incidence of resorptions were evaluated. Groups of at least ele ven mature virgin female hamsters were placed on one of six specific r egimens which started two weeks prior to mating and continued until sa crifice on day nine of pregnancy. Just prior to sacrifice, blood sampl es were drawn by cardiac puncture to measure maternal folic acid level s in red blood cells. The staging of the embryos was based on O'Rahill 's modification of Streeter's developmental horizons in human embryos. Considerable variation was observed in the stage of embryonic develop ment of 9-day-old hamster embryos, both between litter-mates and betwe en litters of the same gestational age. A high overall incidence of op en neural tubes was observed, which did not reflect neural tube closur e failures. A folate-free diet caused retardation of the embryonic dev elopment, although maternal folate levels were unaffected (p < 0.01). The RBC folate levels in the animals which received oral supplementati on with folic acid was significantly higher than that in the unsupplem ented controls (p < 0.001). Folic acid supplementation alone increased the RBC folate level significantly more than combined supplementation with multivitamins (p <0.001). The data indicate that oral supplement ation with folic acid and/or multivitamins produce adequate maternal R BC folate levels. An inadequate maternal folate intake can affect the growth of neurulating embryos even if the maternal RBC folate levels a re still sufficient. This endorses the hypothesis that the beneficial effect of folic acid supplementation on the prevention of neural tube defects is at least partly caused by overriding a relative folic acid shortage due to a metabolic disorder.