Folic Acid and Placental Pathology

Abstract

ArticlePlus Click on the links below to access all the ArticlePlus for this article. Please note that ArticlePlus files may launch a viewer application outside of your web browser. https://links.lww.com/EDE/A157 https://links.lww.com/EDE/A158 To the Editor: Placental abruption (premature placental separation from the uterus) and placental infarction (often resulting from microscopic thrombi or clots within placental blood vessels) are associated with increased risks of stillbirth,1 intrauterine growth restriction,1,2 and preterm delivery.1–3 Folate deficiency has been suggested to be associated with placental abruption and infarction (pooled odds ratio = 26; 95% confidence interval = 0.9–736).4 Canadian white flour has been fortified with folic acid since January 1998. We performed an analysis to determine if there was a change in the rate of placental abruption and infarction in relation to folic acid food fortification. We conducted a retrospective population-based study of the monthly prevalence of placental abruption and infarction (calculated by dividing the number of women hospitalized with a diagnosis of either condition in a given month by all women who gave birth to a live-born or stillborn infant >20 weeks’ gestation age within the same month). The exposure of interest was the mandatory folic acid food fortification, with the prefortification period was defined as January 1, 1995, to September 30, 1998 (allowing a lag effect of 9 months for gestation) and postfortification from October 1, 1998, to March 31, 2001. Pregnancies affected by placental abruption or placental infarction were identified using the Canadian Institute for Health Information Discharge Abstract Database, which contains up to 16 diagnoses, coded by International Classification of Diseases, 9th Revision. Codes used are listed in Appendix 1 (available with the electronic version of this letter). Complete data for the province of Quebec and the Northwest Territories, Yukon and Nunavut, were not available and were excluded. A crude prevalence ratio (PR) compared the prevalence of placental abruption in the periods before and during fortification. Poisson regression was used to adjust the PR for maternal age >35 years, as well as the covariates listed in electronic Appendix 1. These analyses were repeated for placental abruption or placental infarction. All patient identifiers were removed before database extraction. Permission to conduct this study was granted by the Research Ethics Board of Mount Sinai Hospital, Toronto. There were 1,159,329 deliveries before fortification and 695,154 in the period thereafter. Participant characteristics are presented in electronic Appendix 2. Monthly prevalences of placental pathologic events are shown in electronic Appendix 3. No change in association with fortification was observed in the risk of placental abruption in either univariate (1.02; 0.99–1.05) or multivariate analyses (1.02; 0.98–1.05) (Table 1). Similar risk estimates were observed for placental abruption or placental infarction separately.TABLE 1: Risk of Placental Abruption or Infarction in Association With Folic Acid Food FortificationWe had no information on maternal weight or cigarette smoking (risk factors for placental disease), folic acid supplement use, or serum folate concentrations. However, since fortification began, red cell folate concentrations have increased by more than 40% among Canadian women,5 and the relative prevalence of folate deficiency declined by more than 85%.6 Our study included nearly all Canadian women who delivered over a 6-year period, with nearly 100% statistical power to detect as little as a 1% change in the prevalence of placental abruption. Thus, it is unlikely that folic acid can prevent abruption or infarction. ACKNOWLEDGMENTS Supported by the physicians of Ontario through the Physicians’ Services Incorporated Foundation, Sunnybrooke and Women's College Foundation, and John Kingdom. Sarah D. McDonald Clinical Epidemiology Unit Ottawa Hospital Ottawa, Ontario, Canada [email protected] Marian J. Vermeulen Institute for Clinical Evaluative Sciences Toronto, Ontario, Canada Joel G. Ray St. Michael's Hospital, University of Toronto Toronto, Ontario, Canada