{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T07:35:08Z","timestamp":1794468908874,"version":"4.9.1"},"reference-count":48,"publisher":"Cambridge University Press (CUP)","issue":"12","license":[{"start":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T00:00:00Z","timestamp":1495497600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["www.cambridge.org"],"crossmark-restriction":true},"short-container-title":["Public Health Nutr."],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S1368980017000878_abs1\" sec-type=\"general\"><jats:title>Objective<\/jats:title><jats:p>Orofacial clefts (OFC) are the most prevalent craniofacial birth defect. Folic acid (FA) supplementation has been demonstrated as an effective intervention to reduce risk of OFC occurrence. However, the effect of mandatory FA fortification of wheat and\/or maize flour on OFC prevalence has shown controversial results among countries adopting this policy. Thus, we performed a meta-analysis to synthesize the available evidence evaluating the global impact of this mandatory policy on OFC occurrence.<\/jats:p><\/jats:sec><jats:sec id=\"S1368980017000878_abs2\" sec-type=\"general\"><jats:title>Design<\/jats:title><jats:p>Literature search in conventional and grey medical\/scientific databases showed fifteen studies considering OFC prevalence in pre- and post-fortification periods with FA. The effect of this policy was evaluated by computing relative risk (RR) and separating samples into total OFC, non-syndromic forms, cleft lip with or without cleft palate (CL\/P) and cleft palate only (CPO).<\/jats:p><\/jats:sec><jats:sec id=\"S1368980017000878_abs3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>We found a significant effect of FA fortification only on non-syndromic CL\/P (RR=0\u00b788; 95 % CI 0\u00b781, 0\u00b796), whereas neutral effects were detected for total OFC (syndromic plus non-syndromic) and CPO.<\/jats:p><\/jats:sec><jats:sec id=\"S1368980017000878_abs4\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>Our results may reflect the different aetiology of syndromic OFC with respect to non-syndromic forms and the CL\/P related to CPO. Although the number of non-syndromic CL\/P samples was lower than that for total OFC, the absence of both between-study heterogeneity and publication bias leads us to conclude that FA fortification may have beneficial effects on non-syndromic CL\/P.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s1368980017000878","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T10:11:18Z","timestamp":1495534278000},"page":"2260-2268","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":52,"title":["Effects of folic acid fortification on orofacial clefts prevalence: a meta-analysis"],"prefix":"10.1017","volume":"20","author":[{"given":"Natalia","family":"Millacura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Pardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Cifuentes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Suazo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2017,5,23]]},"reference":[{"key":"S1368980017000878_ref36","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20442"},{"key":"S1368980017000878_ref44","doi-asserted-by":"publisher","DOI":"10.1590\/S0036-36342000000600010"},{"key":"S1368980017000878_ref5","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2933"},{"key":"S1368980017000878_ref45","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31381"},{"key":"S1368980017000878_ref15","first-page":"CD007950","article-title":"Effects and safety of periconceptional oral folate supplementation for preventing birth defects","volume":"12","author":"De-Regil","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"S1368980017000878_ref24","doi-asserted-by":"publisher","DOI":"10.1037\/1082-989X.11.2.193"},{"key":"S1368980017000878_ref1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-6343.2007.00398.x"},{"key":"S1368980017000878_ref25","doi-asserted-by":"publisher","DOI":"10.1002\/9780470743386"},{"key":"S1368980017000878_ref41","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyn204"},{"key":"S1368980017000878_ref40","doi-asserted-by":"publisher","DOI":"10.1542\/peds.104.6.e66"},{"key":"S1368980017000878_ref11","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12256"},{"key":"S1368980017000878_ref18","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33479"},{"key":"S1368980017000878_ref28","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v049.i05"},{"key":"S1368980017000878_ref26","unstructured":"Food Fortification Initiative (2016) Mandatory Cereal Grain Legislation. http:\/\/www.ffinetwork.org\/global_progress\/index.php (accessed August 2016)."},{"key":"S1368980017000878_ref47","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyn098"},{"key":"S1368980017000878_ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijom.2012.10.008"},{"key":"S1368980017000878_ref31","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20210"},{"key":"S1368980017000878_ref9","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063852"},{"key":"S1368980017000878_ref32","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30618"},{"key":"S1368980017000878_ref39","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(82)91063-7"},{"key":"S1368980017000878_ref22","first-page":"29","article-title":"Reduction in non syndromic oral clefts following mandatory flour fortification with folic acid in Northern Iran","volume":"28","author":"Golalipour","year":"2014","journal-title":"Med J Islam Repub Iran"},{"key":"S1368980017000878_ref16","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35430"},{"key":"S1368980017000878_ref12","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20315"},{"key":"S1368980017000878_ref42","doi-asserted-by":"publisher","DOI":"10.1007\/PL00014305"},{"key":"S1368980017000878_ref30","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20063"},{"key":"S1368980017000878_ref37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jped.2013.03.010"},{"key":"S1368980017000878_ref34","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20319"},{"key":"S1368980017000878_ref43","unstructured":"National Center for Biotechnology Information, National Institutes of Health (2016) dbSNP Short Genetic Variations. http:\/\/www.ncbi.nlm.nih.gov\/SNP\/ (accessed August 2016)."},{"key":"S1368980017000878_ref35","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/BF03403753","article-title":"Changes in frequencies of select congenital anomalies since the onset of folic acid fortification in a Canadian birth defect registry","volume":"99","author":"Godwin","year":"2008","journal-title":"Can J Public Health"},{"key":"S1368980017000878_ref4","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.10.1853"},{"key":"S1368980017000878_ref6","doi-asserted-by":"publisher","DOI":"10.1177\/154405910808700202"},{"key":"S1368980017000878_ref20","first-page":"198","article-title":"Effects of folic acid fortification in the rates of malformations at birth in Chile","volume":"135","author":"Nazer","year":"2007","journal-title":"Rev Med Chil"},{"key":"S1368980017000878_ref13","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23133"},{"key":"S1368980017000878_ref17","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30651"},{"key":"S1368980017000878_ref19","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20230"},{"key":"S1368980017000878_ref38","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23514"},{"key":"S1368980017000878_ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2011.01.007"},{"key":"S1368980017000878_ref29","doi-asserted-by":"publisher","DOI":"10.1067\/S0022-3476(03)00495-5"},{"key":"S1368980017000878_ref10","doi-asserted-by":"publisher","DOI":"10.1007\/s00412-009-0221-9"},{"key":"S1368980017000878_ref33","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20307"},{"key":"S1368980017000878_ref8","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2000.3027"},{"key":"S1368980017000878_ref2","doi-asserted-by":"publisher","DOI":"10.1597\/09-217"},{"key":"#cr-split#-S1368980017000878_ref23.1","unstructured":"3. Wells GA, Shea B, O'Connell D et al.2014) The Newcastle-Ottawa Scale"},{"key":"#cr-split#-S1368980017000878_ref23.2","unstructured":"4. (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp (accessed August 2016)."},{"key":"S1368980017000878_ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cps.2013.12.003"},{"key":"S1368980017000878_ref27","doi-asserted-by":"publisher","DOI":"10.1037\/met0000046"},{"key":"S1368980017000878_ref21","first-page":"1150","article-title":"Prevalence of congenital malformations at birth in Chilean maternity hospitals","volume":"142","author":"Nazer","year":"2014","journal-title":"Rev Med Chil"},{"key":"S1368980017000878_ref46","doi-asserted-by":"publisher","DOI":"10.1097\/00001665-200303000-00002"}],"container-title":["Public Health Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1368980017000878","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,24]],"date-time":"2019-09-24T23:40:02Z","timestamp":1569368402000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1368980017000878\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,23]]},"references-count":48,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["S1368980017000878"],"URL":"https:\/\/doi.org\/10.1017\/s1368980017000878","relation":{},"ISSN":["1368-9800","1475-2727"],"issn-type":[{"value":"1368-9800","type":"print"},{"value":"1475-2727","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,23]]},"assertion":[{"value":"Copyright \u00a9 The Authors 2017\u00a0","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}