Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands: a population based case-control study
Periconceptional folic acid has been associated with a reduced risk of neural tube defects, but findings on its effect in oral clefts are largely inconclusive. This case-control study assesses the effects of periconceptional folic acid on cleft risk, using complementary data from the Dutch Oral Clef...
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| Veröffentlicht in: | European journal of epidemiology 2013-11, Vol.28 (11), p.875-887 |
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| creator | Rozendaal, Anna M. van Essen, Anthonie J. te Meerman, Gerard J. Bakker, Marian K. van der Biezen, Jan J. Goorhuis-Brouwer, Sieneke M. Vermeij-Keers, Christl de Walle, Hermien E. K. |
| description | Periconceptional folic acid has been associated with a reduced risk of neural tube defects, but findings on its effect in oral clefts are largely inconclusive. This case-control study assesses the effects of periconceptional folic acid on cleft risk, using complementary data from the Dutch Oral Cleft Registry and a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2009. Cases were live-born infants with non-syndromic clefts (n = 367) and controls were infants or foetuses with chromosomal/syndromal (n = 924) or non-folate related anomalies (n = 2,021). We analyzed type/timing/duration of supplement use related to traditional cleft categories as well as to their timing (early/late embryonic periods) and underlying embryological processes (fusion/differentiation defects). Consistent supplement use during the aetiologically relevant period (weeks 0-12 postconception) was associated with an increased risk of clefts (adjusted odds ratio 1.72, 95 % confidence interval 1.19-2.49), especially of cleft lip/alveolus (3.16, 1.69-5.91). Further analysis systematically showed twofold to threefold increased risks for late differentiation defects—mainly clefts of the lip/alveolus—with no significant associations for early/late fusion defects. Effects were attributable to folic acid and not to other multivitamin components, and inclusion of partial use (not covering the complete aetiologically relevant period) generally weakened associations. In conclusion, this study presents several lines of evidence indicating that periconceptional folie acid in the Northern Netherlands is associated with an increased risk of clefts, in particular of cleft lip/alveolus. This association is strengthened by the specificity, consistency, systematic pattern, and duration of exposure-response relationship of our findings, underlining the need to evaluate public health strategies regarding folic acid and to further investigate potential adverse effects. |
| doi_str_mv | 10.1007/s10654-013-9849-0 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1492653955</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>43774911</jstor_id><sourcerecordid>43774911</sourcerecordid><originalsourceid>FETCH-LOGICAL-c457t-687e28c88db1ea6f58997c317af237363496297acefc122049eed3c0a33f3eb63</originalsourceid><addsrcrecordid>eNp9kc1u1TAQhS0EopfCA7AAWUJIbAL-SxyzQxV_UlVYwDrydcbUlyQOHgfUd-PhcJpLQSzYeKTxd86M5hDykLPnnDH9AjlralUxLivTKlOxW2THay0rLVp1m-yYNLISxrATcg_xwBhrmanvkhOhmBFMmR35-RFScHFyMOcQJztQH4fgqHWhpxYxumAz9PRHyJfUTjRMLoHF0kkBv9LoaUxF5AbwGWmCwebwHWiOdIpTVbyKemsXyWgHH9No10lYrGi-BHoRUylpohew1sFOPb6kls5xXoZrlO6vB7ryVmXVnOJAMS_91X1yx9sB4cGxnpLPb15_OntXnX94-_7s1XnlVK1z1bQaROvatt9zsI2vW2O0k1xbL6SWjVSmEUZbB95xsd4FoJeOWSm9hH0jT8mzzXdO8dsCmLsxoIOh7ApxwY4rI5pamrou6JN_0ENcUrnrSjVCrdBqyDfKpYiYwHdzCqNNVx1n3Rptt0XblWi7NdqOFc3jo_OyH6G_UfzOsgBPj4BFVy6d7OQC_uFaJnhZsnBi47B8TV8g_bXif6Y_2kQHzDHdmCqptTKcy1927Mjp</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1462439556</pqid></control><display><type>article</type><title>Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands: a population based case-control study</title><source>MEDLINE</source><source>JSTOR Archive Collection A-Z Listing</source><source>SpringerLink Journals - AutoHoldings</source><creator>Rozendaal, Anna M. ; van Essen, Anthonie J. ; te Meerman, Gerard J. ; Bakker, Marian K. ; van der Biezen, Jan J. ; Goorhuis-Brouwer, Sieneke M. ; Vermeij-Keers, Christl ; de Walle, Hermien E. K.</creator><creatorcontrib>Rozendaal, Anna M. ; van Essen, Anthonie J. ; te Meerman, Gerard J. ; Bakker, Marian K. ; van der Biezen, Jan J. ; Goorhuis-Brouwer, Sieneke M. ; Vermeij-Keers, Christl ; de Walle, Hermien E. K.</creatorcontrib><description>Periconceptional folic acid has been associated with a reduced risk of neural tube defects, but findings on its effect in oral clefts are largely inconclusive. This case-control study assesses the effects of periconceptional folic acid on cleft risk, using complementary data from the Dutch Oral Cleft Registry and a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2009. Cases were live-born infants with non-syndromic clefts (n = 367) and controls were infants or foetuses with chromosomal/syndromal (n = 924) or non-folate related anomalies (n = 2,021). We analyzed type/timing/duration of supplement use related to traditional cleft categories as well as to their timing (early/late embryonic periods) and underlying embryological processes (fusion/differentiation defects). Consistent supplement use during the aetiologically relevant period (weeks 0-12 postconception) was associated with an increased risk of clefts (adjusted odds ratio 1.72, 95 % confidence interval 1.19-2.49), especially of cleft lip/alveolus (3.16, 1.69-5.91). Further analysis systematically showed twofold to threefold increased risks for late differentiation defects—mainly clefts of the lip/alveolus—with no significant associations for early/late fusion defects. Effects were attributable to folic acid and not to other multivitamin components, and inclusion of partial use (not covering the complete aetiologically relevant period) generally weakened associations. In conclusion, this study presents several lines of evidence indicating that periconceptional folie acid in the Northern Netherlands is associated with an increased risk of clefts, in particular of cleft lip/alveolus. This association is strengthened by the specificity, consistency, systematic pattern, and duration of exposure-response relationship of our findings, underlining the need to evaluate public health strategies regarding folic acid and to further investigate potential adverse effects.</description><identifier>ISSN: 0393-2990</identifier><identifier>EISSN: 1573-7284</identifier><identifier>DOI: 10.1007/s10654-013-9849-0</identifier><identifier>PMID: 24092049</identifier><identifier>CODEN: EJEPE8</identifier><language>eng</language><publisher>Dordrecht: Springer</publisher><subject>Adolescent ; Adult ; Biological and medical sciences ; Birth defects ; Cardiology ; Case studies ; Case-Control Studies ; Cleft Lip - epidemiology ; Cleft Lip - prevention & control ; Cleft palate ; Cleft Palate - epidemiology ; Cleft Palate - prevention & control ; Confidence Intervals ; Congenital anomalies ; Congenital diseases ; Dietary Supplements ; Educational relevance ; Embryology ; Epidemiology ; Etiology ; Female ; Folic acid ; Folic Acid - administration & dosage ; Folic Acid - adverse effects ; General aspects ; Humans ; Infants ; Infectious Diseases ; Male ; Maternal Age ; Medical sciences ; Medicine ; Medicine & Public Health ; Metabolic diseases ; Miscellaneous ; Multivariate Analysis ; Neonatal disorders ; Netherlands - epidemiology ; Neural tube defects ; Odds Ratio ; Oncology ; Palate ; PERINATAL EPIDEMIOLOGY ; Population Surveillance ; Pregnancy ; Prenatal care ; Public Health ; Public health. Hygiene ; Public health. Hygiene-occupational medicine ; Risk ; Risk Factors ; Risk reduction ; Socioeconomic Factors ; Time Factors ; Vitamin B ; Vitamin B Complex - administration & dosage ; Vitamin B Complex - adverse effects ; Young Adult</subject><ispartof>European journal of epidemiology, 2013-11, Vol.28 (11), p.875-887</ispartof><rights>2013 Springer Science+Business Media</rights><rights>Springer Science+Business Media Dordrecht 2013</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c457t-687e28c88db1ea6f58997c317af237363496297acefc122049eed3c0a33f3eb63</citedby><cites>FETCH-LOGICAL-c457t-687e28c88db1ea6f58997c317af237363496297acefc122049eed3c0a33f3eb63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/43774911$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/43774911$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,27924,27925,41488,42557,51319,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28021539$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24092049$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rozendaal, Anna M.</creatorcontrib><creatorcontrib>van Essen, Anthonie J.</creatorcontrib><creatorcontrib>te Meerman, Gerard J.</creatorcontrib><creatorcontrib>Bakker, Marian K.</creatorcontrib><creatorcontrib>van der Biezen, Jan J.</creatorcontrib><creatorcontrib>Goorhuis-Brouwer, Sieneke M.</creatorcontrib><creatorcontrib>Vermeij-Keers, Christl</creatorcontrib><creatorcontrib>de Walle, Hermien E. K.</creatorcontrib><title>Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands: a population based case-control study</title><title>European journal of epidemiology</title><addtitle>Eur J Epidemiol</addtitle><addtitle>Eur J Epidemiol</addtitle><description>Periconceptional folic acid has been associated with a reduced risk of neural tube defects, but findings on its effect in oral clefts are largely inconclusive. This case-control study assesses the effects of periconceptional folic acid on cleft risk, using complementary data from the Dutch Oral Cleft Registry and a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2009. Cases were live-born infants with non-syndromic clefts (n = 367) and controls were infants or foetuses with chromosomal/syndromal (n = 924) or non-folate related anomalies (n = 2,021). We analyzed type/timing/duration of supplement use related to traditional cleft categories as well as to their timing (early/late embryonic periods) and underlying embryological processes (fusion/differentiation defects). Consistent supplement use during the aetiologically relevant period (weeks 0-12 postconception) was associated with an increased risk of clefts (adjusted odds ratio 1.72, 95 % confidence interval 1.19-2.49), especially of cleft lip/alveolus (3.16, 1.69-5.91). Further analysis systematically showed twofold to threefold increased risks for late differentiation defects—mainly clefts of the lip/alveolus—with no significant associations for early/late fusion defects. Effects were attributable to folic acid and not to other multivitamin components, and inclusion of partial use (not covering the complete aetiologically relevant period) generally weakened associations. In conclusion, this study presents several lines of evidence indicating that periconceptional folie acid in the Northern Netherlands is associated with an increased risk of clefts, in particular of cleft lip/alveolus. This association is strengthened by the specificity, consistency, systematic pattern, and duration of exposure-response relationship of our findings, underlining the need to evaluate public health strategies regarding folic acid and to further investigate potential adverse effects.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Birth defects</subject><subject>Cardiology</subject><subject>Case studies</subject><subject>Case-Control Studies</subject><subject>Cleft Lip - epidemiology</subject><subject>Cleft Lip - prevention & control</subject><subject>Cleft palate</subject><subject>Cleft Palate - epidemiology</subject><subject>Cleft Palate - prevention & control</subject><subject>Confidence Intervals</subject><subject>Congenital anomalies</subject><subject>Congenital diseases</subject><subject>Dietary Supplements</subject><subject>Educational relevance</subject><subject>Embryology</subject><subject>Epidemiology</subject><subject>Etiology</subject><subject>Female</subject><subject>Folic acid</subject><subject>Folic Acid - administration & dosage</subject><subject>Folic Acid - adverse effects</subject><subject>General aspects</subject><subject>Humans</subject><subject>Infants</subject><subject>Infectious Diseases</subject><subject>Male</subject><subject>Maternal Age</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic diseases</subject><subject>Miscellaneous</subject><subject>Multivariate Analysis</subject><subject>Neonatal disorders</subject><subject>Netherlands - epidemiology</subject><subject>Neural tube defects</subject><subject>Odds Ratio</subject><subject>Oncology</subject><subject>Palate</subject><subject>PERINATAL EPIDEMIOLOGY</subject><subject>Population Surveillance</subject><subject>Pregnancy</subject><subject>Prenatal care</subject><subject>Public Health</subject><subject>Public health. 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Hygiene-occupational medicine</subject><subject>Risk</subject><subject>Risk Factors</subject><subject>Risk reduction</subject><subject>Socioeconomic Factors</subject><subject>Time Factors</subject><subject>Vitamin B</subject><subject>Vitamin B Complex - administration & dosage</subject><subject>Vitamin B Complex - adverse effects</subject><subject>Young Adult</subject><issn>0393-2990</issn><issn>1573-7284</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc1u1TAQhS0EopfCA7AAWUJIbAL-SxyzQxV_UlVYwDrydcbUlyQOHgfUd-PhcJpLQSzYeKTxd86M5hDykLPnnDH9AjlralUxLivTKlOxW2THay0rLVp1m-yYNLISxrATcg_xwBhrmanvkhOhmBFMmR35-RFScHFyMOcQJztQH4fgqHWhpxYxumAz9PRHyJfUTjRMLoHF0kkBv9LoaUxF5AbwGWmCwebwHWiOdIpTVbyKemsXyWgHH9No10lYrGi-BHoRUylpohew1sFOPb6kls5xXoZrlO6vB7ryVmXVnOJAMS_91X1yx9sB4cGxnpLPb15_OntXnX94-_7s1XnlVK1z1bQaROvatt9zsI2vW2O0k1xbL6SWjVSmEUZbB95xsd4FoJeOWSm9hH0jT8mzzXdO8dsCmLsxoIOh7ApxwY4rI5pamrou6JN_0ENcUrnrSjVCrdBqyDfKpYiYwHdzCqNNVx1n3Rptt0XblWi7NdqOFc3jo_OyH6G_UfzOsgBPj4BFVy6d7OQC_uFaJnhZsnBi47B8TV8g_bXif6Y_2kQHzDHdmCqptTKcy1927Mjp</recordid><startdate>20131101</startdate><enddate>20131101</enddate><creator>Rozendaal, Anna M.</creator><creator>van Essen, Anthonie J.</creator><creator>te Meerman, Gerard J.</creator><creator>Bakker, Marian K.</creator><creator>van der Biezen, Jan J.</creator><creator>Goorhuis-Brouwer, Sieneke M.</creator><creator>Vermeij-Keers, Christl</creator><creator>de Walle, Hermien E. 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K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands: a population based case-control study</atitle><jtitle>European journal of epidemiology</jtitle><stitle>Eur J Epidemiol</stitle><addtitle>Eur J Epidemiol</addtitle><date>2013-11-01</date><risdate>2013</risdate><volume>28</volume><issue>11</issue><spage>875</spage><epage>887</epage><pages>875-887</pages><issn>0393-2990</issn><eissn>1573-7284</eissn><coden>EJEPE8</coden><abstract>Periconceptional folic acid has been associated with a reduced risk of neural tube defects, but findings on its effect in oral clefts are largely inconclusive. This case-control study assesses the effects of periconceptional folic acid on cleft risk, using complementary data from the Dutch Oral Cleft Registry and a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2009. Cases were live-born infants with non-syndromic clefts (n = 367) and controls were infants or foetuses with chromosomal/syndromal (n = 924) or non-folate related anomalies (n = 2,021). We analyzed type/timing/duration of supplement use related to traditional cleft categories as well as to their timing (early/late embryonic periods) and underlying embryological processes (fusion/differentiation defects). Consistent supplement use during the aetiologically relevant period (weeks 0-12 postconception) was associated with an increased risk of clefts (adjusted odds ratio 1.72, 95 % confidence interval 1.19-2.49), especially of cleft lip/alveolus (3.16, 1.69-5.91). Further analysis systematically showed twofold to threefold increased risks for late differentiation defects—mainly clefts of the lip/alveolus—with no significant associations for early/late fusion defects. Effects were attributable to folic acid and not to other multivitamin components, and inclusion of partial use (not covering the complete aetiologically relevant period) generally weakened associations. In conclusion, this study presents several lines of evidence indicating that periconceptional folie acid in the Northern Netherlands is associated with an increased risk of clefts, in particular of cleft lip/alveolus. This association is strengthened by the specificity, consistency, systematic pattern, and duration of exposure-response relationship of our findings, underlining the need to evaluate public health strategies regarding folic acid and to further investigate potential adverse effects.</abstract><cop>Dordrecht</cop><pub>Springer</pub><pmid>24092049</pmid><doi>10.1007/s10654-013-9849-0</doi><tpages>13</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0393-2990 |
| ispartof | European journal of epidemiology, 2013-11, Vol.28 (11), p.875-887 |
| issn | 0393-2990 1573-7284 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1492653955 |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing; SpringerLink Journals - AutoHoldings |
| subjects | Adolescent Adult Biological and medical sciences Birth defects Cardiology Case studies Case-Control Studies Cleft Lip - epidemiology Cleft Lip - prevention & control Cleft palate Cleft Palate - epidemiology Cleft Palate - prevention & control Confidence Intervals Congenital anomalies Congenital diseases Dietary Supplements Educational relevance Embryology Epidemiology Etiology Female Folic acid Folic Acid - administration & dosage Folic Acid - adverse effects General aspects Humans Infants Infectious Diseases Male Maternal Age Medical sciences Medicine Medicine & Public Health Metabolic diseases Miscellaneous Multivariate Analysis Neonatal disorders Netherlands - epidemiology Neural tube defects Odds Ratio Oncology Palate PERINATAL EPIDEMIOLOGY Population Surveillance Pregnancy Prenatal care Public Health Public health. Hygiene Public health. Hygiene-occupational medicine Risk Risk Factors Risk reduction Socioeconomic Factors Time Factors Vitamin B Vitamin B Complex - administration & dosage Vitamin B Complex - adverse effects Young Adult |
| title | Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands: a population based case-control study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T16%3A34%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Periconceptional%20folic%20acid%20associated%20with%20an%20increased%20risk%20of%20oral%20clefts%20relative%20to%20non-folate%20related%20malformations%20in%20the%20Northern%20Netherlands:%20a%20population%20based%20case-control%20study&rft.jtitle=European%20journal%20of%20epidemiology&rft.au=Rozendaal,%20Anna%20M.&rft.date=2013-11-01&rft.volume=28&rft.issue=11&rft.spage=875&rft.epage=887&rft.pages=875-887&rft.issn=0393-2990&rft.eissn=1573-7284&rft.coden=EJEPE8&rft_id=info:doi/10.1007/s10654-013-9849-0&rft_dat=%3Cjstor_proqu%3E43774911%3C/jstor_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1462439556&rft_id=info:pmid/24092049&rft_jstor_id=43774911&rfr_iscdi=true |