Neural Tube Defects: Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy generally occurring between days 18-29 of gestation. Ectodermal and mesodermal malformations (mainly involving the skull and vertebrae) may occur as a result of defects of neural tube closure. (From Joynt, Clinical Neurology, 1992, Ch55, pp31-41)Neural Tube: A tube of ectodermal tissue in an embryo that will give rise to the CENTRAL NERVOUS SYSTEM, including the SPINAL CORD and the BRAIN. Lumen within the neural tube is called neural canal which gives rise to the central canal of the spinal cord and the ventricles of the brain. For malformation of the neural tube, see NEURAL TUBE DEFECTS.Anencephaly: A malformation of the nervous system caused by failure of the anterior neuropore to close. Infants are born with intact spinal cords, cerebellums, and brainstems, but lack formation of neural structures above this level. The skull is only partially formed but the eyes are usually normal. This condition may be associated with folate deficiency. Affected infants are only capable of primitive (brain stem) reflexes and usually do not survive for more than two weeks. (From Menkes, Textbook of Child Neurology, 5th ed, p247)Spinal Dysraphism: Congenital defects of closure of one or more vertebral arches, which may be associated with malformations of the spinal cord, nerve roots, congenital fibrous bands, lipomas, and congenital cysts. These malformations range from mild (e.g., SPINA BIFIDA OCCULTA) to severe, including rachischisis where there is complete failure of neural tube and spinal cord fusion, resulting in exposure of the spinal cord at the surface. Spinal dysraphism includes all forms of spina bifida. The open form is called SPINA BIFIDA CYSTICA and the closed form is SPINA BIFIDA OCCULTA. (From Joynt, Clinical Neurology, 1992, Ch55, p34)Folic Acid: A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.Spina Bifida Occulta: A common congenital midline defect of fusion of the vertebral arch without protrusion of the spinal cord or meninges. The lesion is also covered by skin. L5 and S1 are the most common vertebrae involved. The condition may be associated with an overlying area of hyperpigmented skin, a dermal sinus, or an abnormal patch of hair. The majority of individuals with this malformation are asymptomatic although there is an increased incidence of tethered cord syndrome and lumbar SPONDYLOSIS. (From Joynt, Clinical Neurology, 1992, Ch55, p34)Neurulation: An early embryonic developmental process of CHORDATES that is characterized by morphogenic movements of ECTODERM resulting in the formation of the NEURAL PLATE; the NEURAL CREST; and the NEURAL TUBE. Improper closure of the NEURAL GROOVE results in congenital NEURAL TUBE DEFECTS.Spina Bifida Cystica: A form of spinal dysraphism associated with a protruding cyst made up of either meninges (i.e., a MENINGOCELE) or meninges in combination with spinal cord tissue (i.e., a MENINGOMYELOCELE). These lesions are frequently associated with spinal cord dysfunction, HYDROCEPHALUS, and SYRINGOMYELIA. (From Davis et al., Textbook of Neuropathology, 2nd ed, pp224-5)Encephalocele: Brain tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Meningomyelocele: Congenital, or rarely acquired, herniation of meningeal and spinal cord tissue through a bony defect in the vertebral column. The majority of these defects occur in the lumbosacral region. Clinical features include PARAPLEGIA, loss of sensation in the lower body, and incontinence. This condition may be associated with the ARNOLD-CHIARI MALFORMATION and HYDROCEPHALUS. (From Joynt, Clinical Neurology, 1992, Ch55, pp35-6)Vitamin B Complex: A group of water-soluble vitamins, some of which are COENZYMES.Preconception Care: An organized and comprehensive program of health care that identifies and reduces a woman's reproductive risks before conception through risk assessment, health promotion, and interventions. Preconception care programs may be designed to include the male partner in providing counseling and educational information in preparation for fatherhood, such as genetic counseling and testing, financial and family planning, etc. This concept is different from PRENATAL CARE, which occurs during pregnancy.Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation EMBRYO; FETUS; or pregnant female before birth.Food, Fortified: Any food that has been supplemented with essential nutrients either in quantities that are greater than those present normally, or which are not present in the food normally. Fortified food includes also food to which various nutrients have been added to compensate for those removed by refinement or processing. (From Segen, Dictionary of Modern Medicine, 1992)Congenital Abnormalities: Malformations of organs or body parts during development in utero.Folic Acid Deficiency: A nutritional condition produced by a deficiency of FOLIC ACID in the diet. Many plant and animal tissues contain folic acid, abundant in green leafy vegetables, yeast, liver, and mushrooms but destroyed by long-term cooking. Alcohol interferes with its intermediate metabolism and absorption. Folic acid deficiency may develop in long-term anticonvulsant therapy or with use of oral contraceptives. This deficiency causes anemia, macrocytic anemia, and megaloblastic anemia. It is indistinguishable from vitamin B 12 deficiency in peripheral blood and bone marrow findings, but the neurologic lesions seen in B 12 deficiency do not occur. (Merck Manual, 16th ed)Abortion, Therapeutic: Abortion induced to save the life or health of a pregnant woman. (From Dorland, 28th ed)alpha-Fetoproteins: The first alpha-globulins to appear in mammalian sera during FETAL DEVELOPMENT and the dominant serum proteins in early embryonic life.Neural Crest: The two longitudinal ridges along the PRIMITIVE STREAK appearing near the end of GASTRULATION during development of nervous system (NEURULATION). The ridges are formed by folding of NEURAL PLATE. Between the ridges is a neural groove which deepens as the fold become elevated. When the folds meet at midline, the groove becomes a closed tube, the NEURAL TUBE.Infant, Newborn: An infant during the first month after birth.Nervous System: The entire nerve apparatus, composed of a central part, the brain and spinal cord, and a peripheral part, the cranial and spinal nerves, autonomic ganglia, and plexuses. (Stedman, 26th ed)Air Pollution, RadioactiveAmniocentesis: Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions.Prenatal Care: Care provided the pregnant woman in order to prevent complications, and decrease the incidence of maternal and prenatal mortality.Embryo, Mammalian: The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.Amniotic Fluid: A clear, yellowish liquid that envelopes the FETUS inside the sac of AMNION. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (AMNIOCENTESIS).Dietary Supplements: Products in capsule, tablet or liquid form that provide dietary ingredients, and that are intended to be taken by mouth to increase the intake of nutrients. Dietary supplements can include macronutrients, such as proteins, carbohydrates, and fats; and/or MICRONUTRIENTS, such as VITAMINS; MINERALS; and PHYTOCHEMICALS.Mouth Abnormalities: Congenital absence of or defects in structures of the mouth.IrelandGene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.Fetal Death: Death of the developing young in utero. BIRTH of a dead FETUS is STILLBIRTH.Chick Embryo: The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.Flour: Ground up seed of WHEAT.Homocysteine: A thiol-containing amino acid formed by a demethylation of METHIONINE.Vitamin B 12: A cobalt-containing coordination compound produced by intestinal micro-organisms and found also in soil and water. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. INTRINSIC FACTOR is important for the assimilation of vitamin B 12.TailZineb: An agricultural fungicide of the dithiocarbamate class. It has relatively low toxicity and there is little evidence of human injury from exposure.Paired Box Transcription Factors: A family of transcription factors that control EMBRYONIC DEVELOPMENT within a variety of cell lineages. They are characterized by a highly conserved paired DNA-binding domain that was first identified in DROSOPHILA segmentation genes.Methylenetetrahydrofolate Reductase (NADPH2): A flavoprotein amine oxidoreductase that catalyzes the reversible conversion of 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. This enzyme was formerly classified as EC 22.214.171.124.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Embryonic and Fetal Development: Morphological and physiological development of EMBRYOS or FETUSES.Vitamin B 12 Deficiency: A nutritional condition produced by a deficiency of VITAMIN B 12 in the diet, characterized by megaloblastic anemia. Since vitamin B 12 is not present in plants, humans have obtained their supply from animal products, from multivitamin supplements in the form of pills, and as additives to food preparations. A wide variety of neuropsychiatric abnormalities is also seen in vitamin B 12 deficiency and appears to be due to an undefined defect involving myelin synthesis. (From Cecil Textbook of Medicine, 19th ed, p848)Body Patterning: The processes occurring in early development that direct morphogenesis. They specify the body plan ensuring that cells will proceed to differentiate, grow, and diversify in size and shape at the correct relative positions. Included are axial patterning, segmentation, compartment specification, limb position, organ boundary patterning, blood vessel patterning, etc.Methylenetetrahydrofolate Dehydrogenase (NADP): An NADP-dependent oxidoreductase that catalyses the conversion of 5,10-methyleneterahydrofolate to 5,10-methenyl-tetrahydrofolate. In higher eukaryotes a trifunctional enzyme exists with additional METHENYLTETRAHYDROFOLATE CYCLOHYDROLASE and FORMATE-TETRAHYDROFOLATE LIGASE activity. The enzyme plays an important role in the synthesis of 5-methyltetrahydrofolate, the methyl donor for the VITAMIN B12-dependent remethylation of HOMOCYSTEINE to METHIONINE via METHIONINE SYNTHETASE.Notochord: A cartilaginous rod of mesodermal cells at the dorsal midline of all CHORDATE embryos. In lower vertebrates, notochord is the backbone of support. In the higher vertebrates, notochord is a transient structure, and segments of the vertebral column will develop around it. Notochord is also a source of midline signals that pattern surrounding tissues including the NEURAL TUBE development.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Vitamins: Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body.Fetal Diseases: Pathophysiological conditions of the FETUS in the UTERUS. Some fetal diseases may be treated with FETAL THERAPIES.Pregnancy in Diabetics: The state of PREGNANCY in women with DIABETES MELLITUS. This does not include either symptomatic diabetes or GLUCOSE INTOLERANCE induced by pregnancy (DIABETES, GESTATIONAL) which resolves at the end of pregnancy.Embryonic Development: Morphological and physiological development of EMBRYOS.Maneb: Manganese derivative of ethylenebisdithiocarbamate. It is used in agriculture as a fungicide and has been shown to cause irritation to the eyes, nose, skin, and throat.Pregnancy Complications: Conditions or pathological processes associated with pregnancy. They can occur during or after pregnancy, and range from minor discomforts to serious diseases that require medical interventions. They include diseases in pregnant females, and pregnancies in females with diseases.Formate-Tetrahydrofolate Ligase: A carbon-nitrogen ligase that catalyzes the formation of 10-formyltetrahydrofolate from formate and tetrahydrofolate in the presence of ATP. In higher eukaryotes the enzyme also contains METHYLENETETRAHYDROFOLATE DEHYDROGENASE (NADP+) and METHENYLTETRAHYDROFOLATE CYCLOHYDROLASE activity.Gestational Age: The age of the conceptus, beginning from the time of FERTILIZATION. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last MENSTRUATION which is about 2 weeks before OVULATION and fertilization.Thymidine Monophosphate: 5-Thymidylic acid. A thymine nucleotide containing one phosphate group esterified to the deoxyribose moiety.Deanol: An antidepressive agent that has also been used in the treatment of movement disorders. The mechanism of action is not well understood.Teratogens: An agent that causes the production of physical defects in the developing embryo.Pollen Tube: A growth from a pollen grain down into the flower style which allows two sperm to pass, one to the ovum within the ovule, and the other to the central cell of the ovule to produce endosperm of SEEDS.Morphogenesis: The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Folate Receptor 1: A subtype of GPI-anchored folate receptors that is expressed in tissues of epithelial origin. This protein is also identified as an ovarian-tumor-specific antigen.Maternal Exposure: Exposure of the female parent, human or animal, to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals that may affect offspring. It includes pre-conception maternal exposure.Prenatal Nutritional Physiological Phenomena: Nutrition of FEMALE during PREGNANCY.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Abnormalities, Drug-Induced: Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment.Abortion, Induced: Intentional removal of a fetus from the uterus by any of a number of techniques. (POPLINE, 1978)Tetrahydrofolates: Compounds based on 5,6,7,8-tetrahydrofolate.Abnormalities, MultipleCleft Lip: Congenital defect in the upper lip where the maxillary prominence fails to merge with the merged medial nasal prominences. It is thought to be caused by faulty migration of the mesoderm in the head region.Transcobalamins: A group of carrier proteins which bind with VITAMIN B12 in the BLOOD and aid in its transport. Transcobalamin I migrates electrophoretically as a beta-globulin, while transcobalamins II and III migrate as alpha-globulins.Bread: Baked food product made of flour or meal that is moistened, kneaded, and sometimes fermented. A major food since prehistoric times, it has been made in various forms using a variety of ingredients and methods.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Heart Defects, Congenital: Developmental abnormalities involving structures of the heart. These defects are present at birth but may be discovered later in life.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Craniofacial Abnormalities: Congenital structural deformities, malformations, or other abnormalities of the cranium and facial bones.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Pregnancy Trimester, Second: The middle third of a human PREGNANCY, from the beginning of the 15th through the 28th completed week (99 to 196 days) of gestation.Pregnancy Trimester, First: The beginning third of a human PREGNANCY, from the first day of the last normal menstrual period (MENSTRUATION) through the completion of 14 weeks (98 days) of gestation.Thiocholine: A mercaptocholine used as a reagent for the determination of CHOLINESTERASES. It also serves as a highly selective nerve stain.Meningocele: A congenital or acquired protrusion of the meninges, unaccompanied by neural tissue, through a bony defect in the skull or vertebral column.Folate Receptors, GPI-Anchored: Cell surface receptors that bind to and transport FOLIC ACID, 5-methyltetrahydrofolate, and a variety of folic acid derivatives. The receptors are essential for normal NEURAL TUBE development and transport folic acid via receptor-mediated endocytosis.Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Quail: Common name for two distinct groups of BIRDS in the order GALLIFORMES: the New World or American quails of the family Odontophoridae and the Old World quails in the genus COTURNIX, family Phasianidae.Estriol: A hydroxylated metabolite of ESTRADIOL or ESTRONE that has a hydroxyl group at C3, 16-alpha, and 17-beta position. Estriol is a major urinary estrogen. During PREGNANCY, a large amount of estriol is produced by the PLACENTA. Isomers with inversion of the hydroxyl group or groups are called epiestriol.Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, INTRACRANIAL HYPERTENSION; HEADACHE; lethargy; URINARY INCONTINENCE; and ATAXIA.Down Syndrome: A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)Maternal Nutritional Physiological Phenomena: Nutrition of a mother which affects the health of the FETUS and INFANT as well as herself.Cerebral Aqueduct: Narrow channel in the MESENCEPHALON that connects the third and fourth CEREBRAL VENTRICLES.Risk: The probability that an event will occur. It encompasses a variety of measures of the probability of a generally unfavorable outcome.Mice, Neurologic Mutants: Mice which carry mutant genes for neurologic defects or abnormalities.Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion.Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell.Homozygote: An individual in which both alleles at a given locus are identical.