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OBJECTIVE: To assess the evidence of an association between periconceptional folic acid (FA) supplementation or fortification of foods with FA and the risk of twinning, using the Food Standards Australia New Zealand (FSANZ) framework for assessing evidence when substantiating nutrition, health and related claims on foods. DATA SOURCES: The Cochrane Library Database, MEDLINE, MEDLINE in Process, EMBASE, PubMed National Library of Medicine, and CINAHL were searched to identify systematic reviews and primary intervention and observational studies published from 1 July 1994 to 7 July 2006. STUDY SELECTION: One prospective and five retrospective cohort studies that assessed the rate of twinning in populations exposed to FA through supplementation, and six retrospective registry-based cohort studies examining twinning rates after fortification of foods with FA. DATA EXTRACTION: Two reviewers appraised eligible studies and evaluated data independently. DATA SYNTHESIS: The best maximal risk estimates of twinning after FA supplementation were an adjusted odds ratio (adjOR) of 1.26 (95% CI, 0.91-1.73) for preconceptional supplementation and dizygotic twinning and an adjOR of 1.02 (95% CI, 0.85-1.24) for overall twinning. Data from four FA fortification studies in the United States that allowed for calculation of an annual percentage increase showed a maximal annual increase in twinning rates of 4.6%. CONCLUSIONS: Overall, under the FSANZ framework, there is possible evidence for a relationship between periconceptional FA intake and increased twinning. To support this tentative relationship, more well designed, long-term follow-up studies are needed in places where fortification with FA has been introduced, focusing on dose-response and obtaining accurate data on infertility treatments.

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The increased rates of twinning and the increased consumption of folic acid are two parallel processes described in recent years. However, the possible association between an increased incidence of twin pregnancies and periconceptional folic acid supplementation remains controversial. Whereas the data indicating that when folic acid levels are increased to the range required for reducing the incidence of neural tube defects, the data pertaining to the increase in twinning rate are significantly incoherent and are flawed by serious confounders, such as fertility treatments and maternal age. The only plausible theory connecting methyltetrahydrofolate reductase mutation, folic acid, and twinning has not been confirmed. In addition, temporal and dose-effect relationships have not been established. Because of the lack of coherence, questionable plausibility, and no clear dose-effect and temporal relationships, a cause (folic acid supplementation) and effect (increased twinning rate) association cannot be, at present, accepted. Thus, the established policy of peri-conceptional folic acid supplementation to reduce the incidence of neural tube defects should be continued.

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Patients with sickle cell disease routinely take folic acid daily as a supplement to maintain effective erythropoiesis. One of the controversial effects of folic acid is its effect on twin gestation rates. In this report, we present our experience in patients with sickle cell disease and twin pregnancy. Our data show that twin pregnancies seem to be associated with folate supplementation.

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INTRODUCTION: Attention is drawn to the spontaneous incidence of twinning, both dizygotic and monozygotic in different mammalian species. Conjoined twinning, however, only arises when the twinning event occurs at about the primitive streak stage of development, at about 13-14 days after fertilisation in the human, and is exclusively associated with the monoamniotic monochorionic type of placentation. It is believed that the highest incidence of conjoined twinning is encountered in the human. While monozygotic twinning may be induced experimentally following exposure to a variety of agents, the mechanism of induction of spontaneous twinning in the human remains unknown. All agents that are capable of acting as a twinning stimulus are teratogenic, and probably act by interfering with the spindle apparatus. DISCUSSION: The incidence of the various types of conjoined twinning is discussed. Information from the largest study to date indicates that the spontaneous incidence is about 10.25 per million births. The most common varieties encountered were thoraco-omphalopagus (28%), thoracopagus (18.5%), omphalopagus (10%), parasitic twins (10%) and craniopagus (6%). Of these, about 40% were stillborn, and 60% liveborn, although only about 25% of those that survived to birth lived long enough to be candidates for surgery. Conjoined twinning occurs by the incomplete splitting of the embryonic axis and, with the exception of parasitic conjoined twins, all are symmetrical and "the same parts are always united to the same parts". Fusion of monozygotic twins is no longer believed to be the basis of conjoined twinning. Accounts are provided of the anatomical features of each of the commonly encountered varieties.

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OBJECTIVE: To examine the possible role of calcium in conjoined twinning. STUDY DESIGN: Conjoined (CJ) twins are an extreme example of monozygotic (MZ) twinning. Data were collected from various sources on factors to which gravidas who deliver CJ twins were exposed around the time of conception. RESULTS: A significant number of such women were subjected to environmental triggers. Of particular interest is increased CJ twinning following use of oral contraceptives. It is hypothesized that this resulted from prolonged ovulatory dysfunction in lightweight women. The incidence of uniovular twinning is inversely related to women's prepregnancy weights. CONCLUSION: These observations are consistent with the proposed general model of MZ twinning. Factors that induce calcium depression and delayed implantation encourage uniovular duplication in general and CJ twinning in particular.

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