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      The recurrence risk of neural tube defects (NTDs) in a population with high prevalence of NTDs in northern China

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          Although a number of studies have reported the recurrence risk of NTDs in developed countries, there is little data on the rate of recurrence of NTDs in northern China, a region of high prevalence of NTDs.


          Based on the population-based birth defects surveillance system of five counties, we identified women who had an NTD affected pregnancy from 2004-2015 and a retrospective survey was conducted. The rate of recurrence of NTDs was calculated by the number of recurrent NTDs divided by the first NTDs. Maternal age, body mass index (BMI), gestational weeks, education, and occupation were collected. Information on folic acid (FA) supplements, time and dosage were also recorded.


          Among 851 women who had a previous NTD-affected pregnancy, there were 578 subsequent pregnancies, with 10 recurrent NTDs, a 1.7% recurrence rate. The recurrence rate was 1.5% and 2.6% for those taking FA supplements and without FA supplementation respectively. Women with recurrent NTDs had higher BMI before pregnancy compared to those who had a second pregnancy without NTDs. Among the recurrent NTDs, the majority were spina bifida.


          The recurrence rate of NTDs was approximately five times higher than the overall prevalence in the same region of northern China. Risk of recurrence appeared lower among women who took FA supplements. These findings are consistent with the reduction in NTD frequency in the population since introduction of the nationwide FA supplement program. Data on recurrence rates in northern China will inform power calculations for future intervention studies.

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          Most cited references 27

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          Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation.

          The risk of recurrent neural-tube defects is decreased in women who take folic acid or multivitamins containing such during the periconceptional period. The extent to which folic acid supplementation can reduce the first occurrence of defects is not known. 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. Pregnancy was confirmed in 4753 women. The outcome of the pregnancy (whether the fetus or infant had a neural-tube defect or congenital malformation) was known in 2104 women who received the vitamin supplement and in 2052 who received the trace-element supplement. Congenital malformations were significantly more prevalent in the group receiving the trace-element supplement than in the vitamin-supplement group (22.9 per 1000 vs. 13.3 per 1000, P = 0.02). There were six cases of neural-tube defects in the group receiving the trace-element supplement, as compared with none in the vitamin-supplement group (P = 0.029). The prevalence of cleft lip with or without cleft palate was not reduced by periconceptional vitamin supplementation. Periconceptional vitamin use decreases the incidence of a first occurrence of neural-tube defects.
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            Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group.

            A randomised double-blind prevention trial with a factorial design was conducted at 33 centres in seven countries to determine whether supplementation with folic acid (one of the vitamins in the B group) or a mixture of seven other vitamins (A,D,B1,B2,B6,C and nicotinamide) around the time of conception can prevent neural tube defects (anencephaly, spina bifida, encephalocele). A total of 1817 women at high risk of having a pregnancy with a neural tube defect, because of a previous affected pregnancy, were allocated at random to one of four groups--namely, folic acid, other vitamins, both, or neither. 1195 had a completed pregnancy in which the fetus or infant was known to have or not have a neural tube defect; 27 of these had a known neural tube defect, 6 in the folic acid groups and 21 in the two other groups, a 72% protective effect (relative risk 0.28, 95% confidence interval 0.12-0.71). The other vitamins showed no significant protective effect (relative risk 0.80, 95% Cl 0.32-1.72). There was no demonstrable harm from the folic acid supplementation, though the ability of the study to detect rare or slight adverse effects was limited. Folic acid supplementation starting before pregnancy can now be firmly recommended for all women who have had an affected pregnancy, and public health measures should be taken to ensure that the diet of all women who may bear children contains an adequate amount of folic acid.
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              Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention.

              Periconceptional administration of folic acid can reduce a woman's risk of having a fetus or infant with a neural-tube defect. As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 microg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy. Among the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the northern region and 1.0 per 1000 in the southern region. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.0 per 1000 in the northern region and 0.6 per 1000 in the southern region. The greatest reduction in risk occurred among the fetuses or infants of a subgroup of women in the northern region with periconceptional use who took folic acid pills more than 80 percent of the time (reduction in risk, 85 percent as compared with the fetuses or infants of women who registered before their last menstrual period and who took no folic acid; 95 percent confidence interval, 62 to 94 percent) [corrected]. In the southern region the reduction in risk among the fetuses or infants of women with periconceptional use of folic acid was also significant (reduction in risk, 41 percent; 95 percent confidence interval, 3 to 64 percent). Periconceptional intake of 400 microg of folic acid daily can reduce the risk of neural-tube defects in areas with high rates of these defects and in areas with low rates.

                Author and article information

                Impact Journals LLC
                22 September 2017
                3 August 2017
                : 8
                : 42
                : 72577-72583
                1 Institute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health and Family Planning Commission of the People's Republic of China, Peking University, Beijing, P. R. China
                2 Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, P. R. China
                3 UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom
                Author notes
                Correspondence to: Zhiwen Li, lizw@
                Copyright: © 2017 Liu et al.

                This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

                Research Paper

                Oncology & Radiotherapy

                supplementation, china, folic acid, recurrence, neural tube defects


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