Development Of Congenital Defects Research Articles

Consequences of elevated homocysteine during embryonic development and possible modes of action.

Elevated maternal homocysteine (Hcys) is a well-established risk factor for embryonic toxicity and the development of congenital defects, particularly neural tube closure defects and neurocristopathies. The mechanisms responsible are unclear but early work has focused on the role of folate metabolism because these defects are greatly reduced by folate supplementation. As a consequence, elevated Hcys is often looked upon as being an indirect consequence of faulty folate metabolism, although more recent studies show Hcys may act directly as a teratogen. Because Hcys is at the crossroads of protein and DNA metabolism, has a propensity to chemically modify proteins directly, can generate free radicals, and even perturb ligand binding to certain receptors, the developmental processes Hcys can potentially disturb are enumerable. But in recent years, investigators have begun identifying cellular and molecular targets for the direct action of Hcys. While elevating Hcys can alter a myriad of basic cellular activities needed for normal development, our current understanding as to the specific etiological mechanisms responsible for congenital defects is very speculative. Here we provide an overview of what is currently known regarding the toxicity and teratogenicity of elevated Hcys during embryonic development, paying particular attention to neural tube and neural crest cell morphogenesis.

Management issues for women with epilepsy: neural tube defects and folic acid supplementation.

For infants exposed to antiepileptic drugs (AEDs) in utero, the risk for congenital malformations is approximately 4 to 6%, twice the rate reported in the general population. A variety of malformations have been reported in association with prenatal exposure to AEDs. However, a particular association of valproate and carbamazepine with neural tube defects (NTDs)--specifically, with spina bifida aperta (SB)--has been identified. The prevalence of SB is approximately 1 to 2% with valproate exposure and 0.5% with carbamazepine. Reported risk factors for NTDs include previous pregnancy with an NTD, maternal insulin-dependent diabetes mellitus, various nutritional deficiencies and occupational exposures, and high prepregnancy weight. Deficiencies of folate have been implicated in the development of birth defects, including NTDs. The value of periconceptional folic acid supplementation for women in the general population is accepted. However, it is unclear whether folic acid supplementation protects against the embryotoxic and teratogenic effects of AEDs because animal and human studies and case reports have shown variable results. Nevertheless, folic acid supplementation is recommended for women with epilepsy as it is for other women of childbearing age. Even with supplementary folic acid, women taking valproate or carbamazepine should undergo perinatal diagnostic ultrasound to rule out NTDs.

Folate Content of Foods: Comparison Between Databases Compiled Before and After New FDA Fortification Requirements

Folic acid (folate) plays an important role in fetal development and maintenance of health. Inadequate folate intake has been associated with development of birth defects, colon cancer, occlusive heart disease, and brain disorders such as depression, reduced cognition, and Alzheimer's disease. Recognizing that folate intake of many Americans (particularly pregnant women) was insufficient, the U.S. Food and Drug Administration (FDA) ruled in 1996 that folic acid (1.4 μg/g) should be added to all enriched grain products. This rule (CFR 21, Pts 136, 137) became effective on 1 January 1998. The purpose of this study was to examine the effect of this rule on the folic acid content of commonly ingested foods. Folate content of foods eaten by participants of the CSFII survey (1994–1996) was determined upon completion of the CSFII survey and, retrospectively, using a database (SR12 '98) which reflected the new folate regulation. We report that folate levels of baked products, cereal grains, and pasta doubled or tripled after the new regulation took effect. However, even with increased fortification, most baked products and cereal grains still contain about one-fourth the amount of folate (on a μg/100 g basis) than breakfast cereals. Breakfast cereal is still one of the best food sources of folate.

Is the use of insulin lispro safe in pregnancy?

Objective: To provide a review of the use and safety of insulin lispro during pregnancy.Methods: This is a review of the available literature on the use of insulin lispro in pregnancy.A MEDLINE search was performed which included published manuscripts and abstracts in the English language to June 2001.Results: The extensive search revealed that data on insulin lispro useduring pregnancy are limited. Most of the reports on the use of insulin lispro during pregnancy demonstrated improvement of glycemic control, an increase in patient satisfaction, decreased hypoglycemicepisodes, improved maternal and neonatal outcomes, and no deterioration in retinal status. However, there were two reports where it was suggested that there was an association with the use of insulin lisproin pregnancy and increased risk for the development of congenital anomalies and/or development or progression of diabetic retinopathy.Conclusions: Preliminary data suggest that insulin lisprodoes not have adverse maternal or fetal effects during pregnancy in women with diabetes. The use of insulin lispro during pregnancy results in improved glycemic control, fewer hypoglycemic episodes, improvedpatient satisfaction, improved maternal and neonatal outcomes and no deterioration in retinal status. There is no evidence that the use of insulin lispro during pregnancy results in an increased rate ofcongenital malformations. A prospective randomized clinical trial is imperative for further evaluation of any possible association with the use of insulin lispro during pregnancy and an increased rate ofcongenital malformations or change in retinal status.

Analysis of neural tube defects in a mouse mutant using whole embryo culture

The method of whole embryo culture permits a variety of experimental manipulations to be performed on the mammalian embryo. When used in conjunction with mouse mutants, this technique can provide information on the pathogenetic mechanisms underlying the development of birth defects. To illustrate this approach, we review in vitro studies on the development of embryos homozygous for the mutation curly tail ( ct). These studies have involved making repeated observations on individual embryos, performing surgical manipulations, applying environmental influences and metabolic labelling. As a result of this work, we have now partially elucidated the developmental sequence of events that precedes the appearance of spina bifida in the ct mutant.

Observations on the mechanisms of development of congenital anomalies in the rat produced by anti-rat kidney sera.

Observations on the mechanisms of development of congenital anomalies in the rat produced by anti-rat kidney sera.