ABSTRACT
I. Introduction .................................................................................................. 133 II. Folate and Neural Tube Defects ................................................................... 134
III. Folate and Orofacial Clefts ........................................................................... 140 IV. Folate and Congenital Heart Defects ............................................................ 143 V. Folate and Other Birth Defects ..................................................................... 143
A. Urinary Tract Defects .............................................................................. 145 B. Limb Reduction ....................................................................................... 145 C. Trisomy 21 ............................................................................................... 145 D. Omphalocele ............................................................................................ 145 E. Anophthalmia and Microphthalmia ........................................................ 146
VI. Inconclusive Studies on Folate and Birth Defects ........................................ 146 VII. Summary and Conclusions ........................................................................... 146
References ..................................................................................................... 147
The majority of structural birth defects result from a complex interplay between environmental exposures, lifestyle factors, and genetic and epigenetic processes [1-4]. Most defects are isolated, affecting only one organ system, and have no identi ed teratogenic, chromosomal, or genetic etiology [5,6]. The complex mechanistic processes involved in normal and abnormal human embryological development remain only vaguely understood. Fortunately, within the complex orchestration of human development, factors that are both protective and harmful to the developing fetus have been identi ed. It is well established that maternal folic acid intake during the periconceptional period reduces the risk of neural tube defects (NTDs) [7,8] and orofacial clefts [9,10]. There is limited, but still compelling, evidence to indicate that folic acid supplementation also reduces the occurrence of some cardiac defects and that alterations in folate-related mechanisms perturb cardiogenesis. There is
insuf cient but suggestive evidence of an association between maternal folate status and other birth defects, speci cally limb defects [11,12], abdominal wall defects [13,14], and urogenital defects [15].
