J. David Erickson
CENTERS FOR DISEASE CONTROL, BIRTH DEFECTS BRANCH, ATLANTA, GEORGIA, USA
In the early 1990s, randomized controlled trials showed that consumption of vitamin pills containing folic acid before and during early pregnancy could prevent some, but not all, cases of spina bifida and anencephaly. Governmental authorities and professional organizations in different countries reacted in a variety of ways to these new data. In the US, many groups became involved in discussion and debate about the need for action, and about the methods by which actions could be taken. The major outcome of this debate was the decision to fortify the food supply with folic acid.
This was done primarily because of the recognition that a high percentage of pregnancies are unplanned, and that fortification of a staple food might be the most effective approach because it would require little change in behavior of the part of women who could become pregnant. On the other hand, it was realized that the implementation of fortification would take considerable time, that preventable NTD were occurring every day, and that many of these could be prevented through the use of readily available vitamin pills. This, and other considerations, led to the establishment of programs directed at changing the behavior of women of reproductive age to increase their use of vitamin supplements. Some preliminary data on the effects of these efforts, in terms of changes in use of vitamin pills, levels of blood folates in the population, and rates of spina bifida and anencephaly, will be presented.
Source : Frontiers In Fetal Health
Andrew E. Czeizel
FOUNDATION FOR THE COMMUNITY CONTROL OF HEREDITARY DISEASES, BUDAPEST, HUNGARY
There is a breakthrough in the primary prevention of congenital abnormalities, particularly neural tube defects (NTD), that is due to peri-conceptional folic acid or folic acid-containing multivitamin supplementation. The question of practical implications is discussed.
There are two options for the prevention of NTD, but obviously primary prevention is better than the so-called secondary prevention, i.e. elective termination of pregnancy after the diagnosis of severe fetal defects. There are three theoretical possibilities for the primary prevention of NTD: (i) diet rich in folate (unfortunately its efficacy is limited), (ii) supplementation and, (iii) food fortification (discussed previously).
However at the use of peri-conceptional supplementation, there are three debated topics: (1) Folic acid alone or folic acid-containing multivitamin. The efficacy of supplementation depends on the incidence of NTD therefore it is difficult to compare data of different populations. The results of the Hungarian studies showed a higher efficacy (about 90%) of a multivitamin that included 0.8mg folic acid in the prevention of the first occurrence of NTD than folic acid alone. In addition, this treatment may have a preventive effect for cardiovascular, urinary tract and limb defects. Finally, vitamin B12 is an independent factor in the origin of NTD, while vitamin B6 is important in the reduction of hyper-homocysteinemia. (2) The 0.8mg dose of vitamin B11 (i.e., natural folate and synthetic folic acid together) seems to be optimal and recommended. There are two options: 0.4mg folic acid as supplement and 0.4mg folate in diet or 0.6mg of folic acid and 0.2mg folate, however, the upper tolerable dose of folic acid is 1.0mg for healthy including pregnant women. (3) The previous recommendation (4.0mg folic acid) for the reduction of recurrent NTD is old-fashioned. A multivitamin including a physiological dose (less than 1.0mg) of folic acid seems to be better: its efficacy is greater, cheaper (there is no need for medical supervision) and, a lower rate of adverse effects is expected.
Thus, my suggestion is to use 0.4mg to 0.8mg folic acid-containing multivitamin per day for all women who are capable of becoming pregnant and for women who have previously had a NTD- affected offspring during peri-conceptional period.
Source : Frontiers In Fetal Health
Roger E. Stevenson, Julianne S. Collins, Jane H. Dean
South Carolina Birth Defects Surveillance and Prevention Program
Objective: To determine if folic acid protects against NTDs with other malformations or only against isolated NTDs.
Methods: Active and passive surveillance methods were used to determine the rates of isolated NTDs and NTDs with other malformations that occurred in South Carolina between October 1992 - September 2000. During this time period, the use of folic acid supplements by women of childbearing age increased from 8% to 35%.
Results: The overall rate of NTDs decreased from 18.6 to 9.4 per 10,000 live births and fetal deaths (p<0.0001). Isolated NTDs decreased from 14.3 to 8.1 cases per 10,000 live births and fetal deaths (p<.0001), and NTDs with other malformations decreased from 4.3 to 1.3 cases per 10,000 live births and fetal deaths (p=0.0165).
Conclusions: Folic acid's protective effect against isolated neural tube defects has been documented in nonrandomized trials, observational studies, and randomized control studies. Intervention trials from China, Texas, South Carolina and the United Kingdom have also confirmed the inverse relationship between folic acid use and the rate of isolated neural tube defects. Evidence that folic acid might also have a protective effect against other malformations was seen in the Medical Research Council’s recurrence prevention study, in the Hungarian occurrence prevention study, and in several investigations since then. Experience in South Carolina’s Birth Defects Surveillance and Prevention Program provides additional evidence that periconceptional use of folic acid may protect against other malformations. The type of other malformations subject to protective benefits of folic acid will require additional study
Source : Frontiers In Fetal Health
D.K. Waller, J.L. Anderson, W. Nembhard, A. Scheuerle, D. Wright, M. Canfield
Texas Birth Defects Research Center
Objective: Our goal was to examine the association between maternal dieting and
diet-related behaviors in the periconceptional period and the risk of having offspring affected by neural tube defects.
Methods: We analyzed data from a CDC-funded telephone interview of 112 mothers of infants and fetuses with neural tube defects (NTDs) from the Texas Birth Defects Registry and 226 mothers of control infants.
Results: Women who reported dieting during the periconceptional period had no increase in the risk of NTDs (odds ratio 1.3, 95% CI 0.7 to 2.2). Mothers who reported they ate little or no food for a day or more during this period also had no increase in the risk of NTDs (odds ratio 1.4, 95% CI 0.8 to 2.5). For diet-related behaviors a preliminary analysis revealed a significant association between use of laxatives (odds ratio 3.0, 95% CI 1.2 to 7.4) pep pills (odds ratio 4.7, 95% CI 1.2 to 18.9) and vomiting (odds ratio 2.8, 95% CI 1.0 to 7.9) in the periconceptional period and an increased risk of having an infant with an NTD. A non-significant positive association was observed for use of diuretics (odds ratio 2.0, 95% CI 0.5 to 9.0).
Conclusions: These results are preliminary and should therefore be interpreted cautiously. These diet-related behaviors may serve as markers for more severe diets, which may be associated with an increased risk of NTDs. They may also be associated with increased risk of an NTD, independently of dieting. We plan to conduct a more in-depth analysis of dieting and diet-related behaviors, and potential confounders that will include a larger number of cases and controls.
Source : Frontiers In Fetal Health
M Felkner, K Hendricks, L Suarez, R Larsen, K Waller
Texas Department of Health Neural Tube Defect Project 1995-1999
Objective: To assess associations between periconceptional diarrhea and periconceptional oral antimicrobial use and the risk of neural tube defects
Methods: In June 1995 a case-control study was initiated by the Texas Department of Health among Mexican American women residing in the fourteen counties of the Texas-Mexico border. Case mothers had carried infants with neural tube defect. Control mothers had given birth to infants without neural tube defects. The case-control protocol included a general questionnaire which elicited information regarding illnesses experienced and antibiotics taken from three months prior to conception to three months after conception.
Results: The unadjusted association of diarrhea and risk of neural tube defect was significant (OR=3.3, CI=1.4 to 7.6). The unadjusted association of use of oral antimicrobials and risk of neural tube defect was also significant (OR=3.4, CI=1.6 to 7.3). These associations persisted among women who had no fever during the periconceptional period and were present irrespective of folate intake. Diarrhea was associated with an increased risk of NTD independent of use of antimicrobials. The converse was also true; antimicrobials were associated with an increased risk of NTD independent of diarrhea.
Conclusions and Implications: Further research regarding these potentially modifiable risk factors is warranted. Replication of these findings could result in interventions in addition to folate supplementation.
Source : Frontiers In Fetal Health
Sebastiano Bianca, MD, Giuseppe Ettore, MD
SICILIAN REGISTRY OF CONGENITAL MALFORMATIONS (I.S.MA.C. REGISTRY), CATANIA, ITALY
In the published literature, there is an epidemiological association between pregnancies that result in a neural tube defect or congenital cardiovascular malformations and spontaneous abortion at any time in gestation in the immediately preceding pregnancy.
To verify this association in our population, we compared the rate of spontaneous abortion in a preceeding pregnancy between women whose fetus and/or liveborn infant was diagnosed with congenital cardiovascular malformations (CCVM) or neural tube defects (NTD) and a control group of 3,318 mothers whose newborns were born with congenital malformations other than CCVM or NTD.
From our 1991-1996 data in the Sicilian Registry of Congenital Malformations (I.S.MA.C. Registry), we identified 928 cases of CCVM, 112 cases of NTD and a control group of 3,318 newborns with congenital malformations other than CCVM or NTD.
Spontaneous abortion in the preceding pregnancy was reported in 28.7% of the cases with CCVM and in 25.1% of the cases with NTD compared with the 8.6% of cases with other malformations (p<0.05 for CCVM and p<0.02 for NTD. This difference was independent of the maternal age and the type and severity of malformation.
Upon further evluation of the reproductive histories, we found that in 62.1% of cases of CCVM there was only one spontaneous abortion, in 25.8% there were two and in 12.1%, three or more abortions preceding delivery of the newborn with CCVM. In the NTD cases, we found 64.4% with one abortion, 28.5% with two and 7.1% with three or more. Some authors have proposed a "trophoblastic cell rest theory" to explain this epidemiological association. We believe that in order to study the teratogenic potential of remnants of a previous pregnancy on a developing embryo larger studies will need to confirm whether an epidemiological association exists between a previous spontaneous abortion and subsequent CCVM or NTD. We think that genetic hypothesis cannot be ruled out specially for the cases with an high abortion rate in the reproductive history. Only better knowledge of the genetic mechanisms involved in CCVM and NTD will explain this epidemiological association.
References
Bianca S, Ettore G, Guarnera S, et al. The relathionship between congenital cardiovascular malformations and spontaneous abortion in preceding pregnancy. Paediat Perinatal Epidemiol 1999;13:236.
Carmi R, Gohar J, Meizner I, et al. Spontaneous abortion Ð high risk factor for neural tube defect in subsequent pregnancy. Am J Medl Genet 1994;51:93-7.
Gardiner A, Clarke C, Cowen J, et al. Spontaneous abortion and fetal abnormality in subsequent pregnancy. Br Med J 1978;1:1016-18.
KurinczuK JJ, Clarke M. A case-control study to investigate the role of recent spontaneous abortion in the etiology of neural tube defects. Paediat Perinatal Epidemiol 1993;7:167-76.
Sheiner E, Katz M, Fraser D, et al. The relationship between congenital cardiovascular malformations and spontaneous abortion in preceding pregnancy. Paediat Perinatal Epidemiol 1998;12:128-35.
Source : Frontiers In Fetal Health