First Occurrence Of Neural Tube Defects Research Articles

Effect of periconceptional folic acid supplementation on the risk of neural tube defects associated with a previous spontaneous abortion or maternal first-trimester fever.

Does maternal periconceptional no folic acid supplementation have an increased risk of neural tube defects (NTDs) associated with previous spontaneous abortion or first-trimester fever? Maternal periconceptional no folic acid supplementation can increase the risk of NTDs associated with previous spontaneous abortion or first-trimester fever, independent of known confounding factors. Maternal periconceptional folic acid deficiency can increase the risk of NTDs. However, whether an interaction between periconceptional no folic acid supplementation and history of spontaneous abortion or first-trimester fever may have an increased risk of NTDs remains unknown. A population-based case-control study was performed including 104 nuclear families with offspring with NTDs and 100 control families with normal offspring between 1993 and 2002. We investigated the potential interaction between periconceptional no folic acid use and a maternal history of spontaneous abortion or first-trimester fever in the risk for NTDs. Information on exposure factors was obtained at the onset of pregnancy, and pregnancy outcomes were collected during the first week after delivery or at the time of termination of the pregnancy. A multivariate logistic regression analysis was performed. The interaction between periconceptional no folic acid use and a maternal history of spontaneous abortion markedly increased the risk of NTDs (adjusted odds ratio (aOR) 18.68, 95% CI, 4.43-78.76) after adjusting for potential confounding factors. The interaction coefficient was found to be 2.08, higher than 1, indicating that there is a significant interaction between two factors. Mothers who did not take periconceptional folic acid and had first-trimester fever had an increased risk of NTDs (aOR 21.81, 95% CI, 8.81-80.73). However, the interaction coefficient was found to be 0.62, less than 1, indicating that there is no significant interaction between two factors. A potential limitation was that the interval between the previous spontaneous abortion and the beginning of the subsequent pregnancy could not be estimated accurately, but was at least 1year or more. We emphasize that a previous spontaneous abortion may represent a first occurrence of NTDs rather than be the cause of NTDs. Our findings indicate that mothers with a history of spontaneous abortion are ideal candidates for periconceptional folic acid supplementation. This work was supported by National Natural Science Foundation of China (41871360) and Danone Nutrition Center for Dietary Nutrition Research and Education Foundation (DIC2015-05). There are no competing interests to declare.

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Periconceptional folic acid and multivitamin supplementation for the prevention of neural tube defects and other congenital abnormalities

The pioneering studies of Smithells et al. showed the reduction of recurrent neural-tube defects (NTD) after periconceptional folic acid-containing multivitamin supplementation. The Hungarian Periconceptional Service was established in 1984, and this primary health care system offered a chance to organize a randomized controlled trial to check whether the supplementation of a multivitamin containing 0.8 mg of folic acid during the periconceptional period is appropriate for the reduction of a first occurrence of NTD in the family. This found a reduction of approximately 90% of primary NTD. An unexpected finding was a significant reduction in the rate of congenital abnormalities overall: 20.6 per 1000 in the 'multivitamin' group, and 40.6 per 1000 in the 'trace-element-like' placebo group (RR = 0.53, 95% CI: 0.35-0.70). When the 6 cases of NTD were excluded, this difference in the rates of major congenital abnormalities between the two study-groups remained very highly significant (p < 0.0001). Cardiovascular malformations and urinary tract defects were particularly affected. These findings were confirmed in the Hungarian cohort-controlled trial and by observational studies in other countries. Two questions remain to be answered. Is folic acid better alone or with multivitamins? What is the optimal dose of folic acid? Overall, the Hungarian experiences of periconceptional care have shown not only primary prevention of several severe congenital abnormalities but also a good cost-benefit balance.

The role of pharmacoepidemiology in pharmacovigilance: rational drug use in pregnancy.

The most important objective of the Hungarian Case-Control Surveillance of Congenital Abnormalities is the postmarketing surveillance of the teratogenic effects of drugs. This dataset includes 22,865 pregnant women who had offspring with congenital abnormalities and 38,151 pregnant women who had healthy babies between 1980 and 1996. Their case-control analysis is appropriate to assess the risks and benefits of drug treatments during pregnancy. Of about 4000 drugs used in Hungary, 35 seemed to be human teratogens. Only a small proportion (about 1%) of congenital abnormalities is traceable to teratogenic drugs in humans. Hungarian studies were not able to confirm the teratogenicity of tetracyclines (doxycycline) and some other drugs, but indicated the beneficial effect of clotrimazole in the prevention of undescended testis related to preterm birth. Periconceptional multivitamin/folic acid supplementation can reduce the first occurrence of neural-tube defects, oral clefts, cardiovascular malformations, and urinary tract defects. At present the teratogenicity of drugs is exaggerated and the benefits of drug treatment during pregnancy are underestimated. This unbalanced risk-benefit assessment initiated disadvantageous decisions, e.g. planned pregnancies are terminated because of the supposed false teratogenic risk of drugs; pregnant women with acute or chronic diseases are not treated adequately and it causes exacerbation of the illness or fetal complications; the necessary drug treatments are connected with a permanent psychological stress. In conclusion, the anxiety and fear created by the notion that nearly all drugs cause congenital abnormalities is more harmful than the effect of proven human teratogenic drugs themselves.

Prevention of the First Occurrence of Neural-Tube Defects by Periconceptional Vitamin Supplementation

Prevention of the First Occurrence of Neural-Tube Defects by Periconceptional Vitamin Supplementation

Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation: Czeizel AE, Dudas I. N Engl J Med 1992;327:1832–1835

Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation: Czeizel AE, Dudas I. N Engl J Med 1992;327:1832–1835

Prevention of the First Occurrence of Neural-Tube Defects by Periconceptional Vitamin Supplementation

Abstract Background. The risk of recurrent neural-tube defects is decreased in women who take folic acid or multivitamins containing folic acid during the periconceptional period. The extent to which such supplementation can reduce the first occurrence of defects is not known. Methods. We conducted a randomized, controlled trial of periconceptional multivitamin supplementation to test the efficacy of this treatment in reducing the incidence of a first occurrence of neural-tube defects. Women planning a pregnancy (in most cases their first) were randomly assigned to receive a single tablet of a vitamin supplement (containing 12 vitamins, including 0.8 mg of folic acid; 4 minerals; and 3 trace elements) or a trace-element supplement (containing copper, manganese, zinc, and a very low dose of vitamin C) daily for at least one month before conception and until the date of the second missed menstrual period or later. Results. Pregnancy was confirmed in 4753 women. The outcome of the pregnancy (whether the fetu...

Medical genetics: advances in brief: Prevention of the first occurrence of neural-tube defects by periconceptual vitamin supplementation

Medical genetics: advances in brief: Prevention of the first occurrence of neural-tube defects by periconceptual vitamin supplementation