The Absence of a Relation between the Periconceptional Use of Vitamins and Neural-Tube Defects

Abstract

Whether taking multivitamins or folate around the time of conception can reduce a woman's risk of having a child with a neural-tube defect is controversial. To investigate this question, we examined the periconceptional use of vitamin supplements by women who had a conceptus with a neural-tube defect (n = 571), women who had had a stillbirth or a conceptus with another malformation (n = 546), and women who had had a normal conceptus (n = 573). Women with conceptuses with neural-tube defects were identified either prenatally or postnatally and were matched to control mothers for gestational age. To minimize recall bias, we interviewed nearly all the women within five months of the diagnosis of a birth defect or the birth of the infant (mean, 84 days); information on vitamin use was obtained by an interviewer who was unaware of the outcome of pregnancy. The rate of periconceptional multivitamin use among the mothers of infants with neural-tube defects (15.8 percent) was not significantly different from the rate among mothers in either the abnormal or the normal control group (14.1 percent and 15.9 percent, respectively). After adjustment for potential confounding factors, the odds ratio for having an infant with a neural-tube defect among women classified as having had full supplementation with multivitamins was 0.95 as compared with the mothers of the abnormal infants (95 percent confidence interval, 0.78 to 1.14) and 1.00 as compared with the mothers of normal infants (95 percent confidence interval, 0.83 to 1.20). There were no differences among the groups in the use of folate supplements. The adjusted odds ratio for having an infant with a neural-tube defect among those receiving the recommended daily allowance of folate was 0.97 as compared with the mothers of abnormal infants (95 percent confidence interval, 0.79 to 1.18) and 0.98 as compared with the mothers of normal infants (95 percent confidence interval, 0.80 to 1.20). We conclude that the periconceptional use of multivitamins or folate-containing supplements by American women does not decrease the risk of having an infant with a neural-tube defect.

Folate intake in Europe: recommended, actual and desired intake

“…NTDs in such areas probably have a genetic basis or originates from other causes than a lack of folic acid . Furthermore, women who started the use of supplements after conception seem to be classi®ed as`non-users' (Mills et al, 1989), whereas other observational studies have indicated that folic acid can also be protective in this period (Milunsky et al, 1989;Bower & Stanley, 1989;Shaw et al, 1995). Other reasons could be the broad range of central nervous system defects that were included as cases in both studies (Winship et al, 1984;Mills et al, 1989).…”

“…In two case-control studies the reduction in the risk of an NTD-affected birth was not signi®cant (Winship et al, 1984;Mills et al, 1989). The study of Winship et al, (1984) lacked information on the use of non-prescribed drugs (of which folic acid is a common one) and on the use of drugs prescribed by hospital physicians.…”

“…The study of Winship et al, (1984) lacked information on the use of non-prescribed drugs (of which folic acid is a common one) and on the use of drugs prescribed by hospital physicians. The zero ®nding in the study of Mills et al (1989) may be caused by the low prevalence of NTDs in the geographic area. NTDs in such areas probably have a genetic basis or originates from other causes than a lack of folic acid .…”

Folic acid and neural tube defects

“…For women without a prior history of NTDs, 4 of 5 studies reported decreases of 40% to 100% if folic acid was taken on a daily basis. [3][4][5][6][7][8] For women with a prior history of NTDs, all published studies reported a similar reduction after folic acid supplementation. 9 -12 The dose of folic acid, either alone or part of a multivitamin preparation, varied between 400 to 5000 g (0.4 -5 mg) per day and was taken at least 1 month before conception and throughout the first trimester.…”

Preconceptional folic acid supplementation in Japan

“…by 30–70% (Laurence et al 1981; Smithells et al 1983; Mulinare et al 1988; Mills et al 1989; Milunsky et al 1989; MRC Vitamin Study Research Group 1991; Saitsu et al 2003), leading to an international consensus on the importance of preconceptional FA supplementation. In Japan, despite the efforts of JSOG and JAOG, preconceptional FA supplementation was not universally accepted.…”