162. THE EFFECT OF MATERNAL FOLIC ACID SUPPLEMENTATION THROUGHOUT PREGNANCY ON NEURODEVELOPMENT, MOTOR FUNCTION AND BEHAVIOUR OF PROGENY IN THE RAT

Abstract

Background: Maternal folic acid supplementation (mFAS) during early pregnancy is recommended to reduce the incidence of neural tube defects and has recently been associated with improved neurodevelopment in children. However, the effect on neurodevelopment of mFAS from before conception and throughout pregnancy is unknown. We examined the effect of mFAS throughout the gestational period on postnatal growth, neurodevelopment and early adult motor function and behaviour in rat offspring. Methods: Female Wistar Rats were fed either a control (folic acid 2mg/kg, n=6) or moderate mFAS diet (folic acid 6mg/kg, n=6) from two weeks before mating with Lewis males, until birth of progeny. Male and female progeny (Control=36, mFAS=36) were weighed on postnatal day (PD) 3, 7, 14, 21, 40 and 90, and underwent various tests between PD4 and 14: righting reflex, palm-grasp reflex, negative geotaxis, forelimb hanging, ascent test and eye opening. Locomotor/ exploratory behaviour, motor coordination and anxiety were assessed using an open field test (PD52), rotarod (PD55) and elevated plus maze (PD58) (Control=24, mFAS=24). Results: mFAS did not alter maternal weight gain, litter-size at birth or progeny growth between PD3-90. mFAS tended to increase righting reflex time (p=0.057) and impair ascent ability (p=0.085). Negative geotaxis time was reduced at PD7 but not later (Diet x Age p=0.051). mFAS increased the proportion of progeny with eyes open at PD14 (p=0.008) and tended to increase forelimb hanging time(p=0.097). mFAS did not alter motor learning/function (rotarod), but increased ambulatory and exploratory behaviour (open field test; p=0.027). Conclusions: mFAS delays some early aspects of neurodevelopment including neonatal postural reflex maturation and proprioceptive/vestibular function, but accelerates others such as eye opening. However, the open field test indicated that mFAS improved the offspring's locomotion and exploratory behaviours in adulthood. Further studies will differentiate the neurodevelopmental effects of mFAS around conception from gestation-long mFAS.