Retinoic Acid Embryopathy
Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed...
Gespeichert in:
| Veröffentlicht in: | The New England journal of medicine 1985-10, Vol.313 (14), p.837-841 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 841 |
|---|---|
| container_issue | 14 |
| container_start_page | 837 |
| container_title | The New England journal of medicine |
| container_volume | 313 |
| creator | Lammer, Edward J Chen, Diane T Hoar, Richard M Agnish, Narsingh D Benke, Paul J Braun, John T Curry, Cynthia J Fernhoff, Paul M Grix, Art W Lott, Ira T Richard, James M Sun, Shyan C |
| description | Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively. The outcomes in this cohort were 8 spontaneous abortions, 23 normal infants, and 5 malformed infants. Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5).
Among the 21 malformed infants we found a characteristic pattern of malformation involving craniofacial, cardiac, thymic, and central nervous system structures. The malformations included microtia/anotia (15 infants), micrognathia (6), cleft palate (3), conotruncal heart defects and aortic-arch abnormalities (8), thymic defects (7), retinal or optic-nerve abnormalities (4), and central nervous system malformations (18). The pattern of malformation closely resembled that produced in animal studies of retinoid teratogenesis. It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations. (N Engl J Med 1985;313:837–41.)
Retinoic acids are analogues of vitamin A that display some of its biologic activities. Retinoic acids cannot replace the visual or reproductive functions of vitamin A, but they can assume its roles in stimulating bone growth and epithelial differentiation. Because of their effects on epithelial-cell differentiation and their relatively low toxicity as compared with vitamin A, retinoic acids were developed for the treatment of severe cystic acne and other chronic dermatoses.
1
,
2
The first of these retinoic acids, isotretinoin (13-
cis
-retinoic acid), was licensed in the United States in September 1982 with the brand name Accutane. According to marketing research . . . |
| doi_str_mv | 10.1056/NEJM198510033131401 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1878434926</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4320952125</sourcerecordid><originalsourceid>FETCH-LOGICAL-c455t-c9d9ba33d11f6282285fc7982410db9554a07d32fe44f17c60a90e657515a35b3</originalsourceid><addsrcrecordid>eNp9kM1Lw0AQxRdRaq3-ASJCQW8Sndmv7B5LqV9UBdHzstlsMKVJ6m56yH9vpKEncS5zmN97j3mEXCDcIgh597p4fkGtBAIwhgw54AEZo2As4RzkIRkDUJXwVLNjchLjCvpBrkdkxFBSBByT83fflnVTuunMlfl0UWWhaza2_epOyVFh19GfDXtCPu8XH_PHZPn28DSfLRPHhWgTp3OdWcZyxEJSRakShUu1ohwhz7QQ3EKaM1p4zgtMnQSrwUuRChSWiYxNyNXOdxOa762PrVk121D3kQZVqjjjmsqeYjvKhSbG4AuzCWVlQ2cQzG8b5o82etXl4L3NKp_vNcP7_f16uNvo7LoItnZl3GOKA5dIe-xmh1VVNLVfVf-G_gCcom8A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1878434926</pqid></control><display><type>article</type><title>Retinoic Acid Embryopathy</title><source>MEDLINE</source><source>ProQuest Central UK/Ireland</source><creator>Lammer, Edward J ; Chen, Diane T ; Hoar, Richard M ; Agnish, Narsingh D ; Benke, Paul J ; Braun, John T ; Curry, Cynthia J ; Fernhoff, Paul M ; Grix, Art W ; Lott, Ira T ; Richard, James M ; Sun, Shyan C</creator><creatorcontrib>Lammer, Edward J ; Chen, Diane T ; Hoar, Richard M ; Agnish, Narsingh D ; Benke, Paul J ; Braun, John T ; Curry, Cynthia J ; Fernhoff, Paul M ; Grix, Art W ; Lott, Ira T ; Richard, James M ; Sun, Shyan C</creatorcontrib><description>Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively. The outcomes in this cohort were 8 spontaneous abortions, 23 normal infants, and 5 malformed infants. Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5).
Among the 21 malformed infants we found a characteristic pattern of malformation involving craniofacial, cardiac, thymic, and central nervous system structures. The malformations included microtia/anotia (15 infants), micrognathia (6), cleft palate (3), conotruncal heart defects and aortic-arch abnormalities (8), thymic defects (7), retinal or optic-nerve abnormalities (4), and central nervous system malformations (18). The pattern of malformation closely resembled that produced in animal studies of retinoid teratogenesis. It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations. (N Engl J Med 1985;313:837–41.)
Retinoic acids are analogues of vitamin A that display some of its biologic activities. Retinoic acids cannot replace the visual or reproductive functions of vitamin A, but they can assume its roles in stimulating bone growth and epithelial differentiation. Because of their effects on epithelial-cell differentiation and their relatively low toxicity as compared with vitamin A, retinoic acids were developed for the treatment of severe cystic acne and other chronic dermatoses.
1
,
2
The first of these retinoic acids, isotretinoin (13-
cis
-retinoic acid), was licensed in the United States in September 1982 with the brand name Accutane. According to marketing research . . .</description><identifier>ISSN: 0028-4793</identifier><identifier>EISSN: 1533-4406</identifier><identifier>DOI: 10.1056/NEJM198510033131401</identifier><identifier>PMID: 3162101</identifier><identifier>CODEN: NEJMAG</identifier><language>eng</language><publisher>Boston, MA: Massachusetts Medical Society</publisher><subject>Abnormalities, Drug-Induced - etiology ; Abortion ; Abortion, Spontaneous - chemically induced ; Acids ; Acne ; Acne Vulgaris - drug therapy ; Adolescent ; Adult ; Age ; Babies ; Biological and medical sciences ; Birth control ; Birth defects ; Case reports ; Central nervous system ; Children & youth ; Cleft lip/palate ; Disease control ; Drug toxicity and drugs side effects treatment ; Female ; Fetal Death - chemically induced ; Fetuses ; Heart ; Heart Defects, Congenital - chemically induced ; Heart diseases ; Hospitals ; Humans ; Infant, Newborn ; Infants ; Isotretinoin ; Laboratory animals ; Male ; Medical sciences ; Medicine ; Microtia ; Miscellaneous (drug allergy, mutagens, teratogens...) ; Morphogenesis ; Pediatrics ; Pharmacology. Drug treatments ; Pregnancy ; Pregnancy Trimester, First ; Prenatal exposure ; Prospective Studies ; Retina ; Retinoic acid ; Retrospective Studies ; Risk ; Rodents ; Teratogenesis ; Teratogenicity ; Thymus ; Tretinoin - adverse effects ; Tretinoin - therapeutic use ; Vitamin A ; Womens health</subject><ispartof>The New England journal of medicine, 1985-10, Vol.313 (14), p.837-841</ispartof><rights>1986 INIST-CNRS</rights><rights>Copyright Massachusetts Medical Society Oct 3, 1985</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-c9d9ba33d11f6282285fc7982410db9554a07d32fe44f17c60a90e657515a35b3</citedby><cites>FETCH-LOGICAL-c455t-c9d9ba33d11f6282285fc7982410db9554a07d32fe44f17c60a90e657515a35b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1878434926?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>315,782,786,27933,27934,64394,64398,72478</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=8404612$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3162101$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lammer, Edward J</creatorcontrib><creatorcontrib>Chen, Diane T</creatorcontrib><creatorcontrib>Hoar, Richard M</creatorcontrib><creatorcontrib>Agnish, Narsingh D</creatorcontrib><creatorcontrib>Benke, Paul J</creatorcontrib><creatorcontrib>Braun, John T</creatorcontrib><creatorcontrib>Curry, Cynthia J</creatorcontrib><creatorcontrib>Fernhoff, Paul M</creatorcontrib><creatorcontrib>Grix, Art W</creatorcontrib><creatorcontrib>Lott, Ira T</creatorcontrib><creatorcontrib>Richard, James M</creatorcontrib><creatorcontrib>Sun, Shyan C</creatorcontrib><title>Retinoic Acid Embryopathy</title><title>The New England journal of medicine</title><addtitle>N Engl J Med</addtitle><description>Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively. The outcomes in this cohort were 8 spontaneous abortions, 23 normal infants, and 5 malformed infants. Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5).
Among the 21 malformed infants we found a characteristic pattern of malformation involving craniofacial, cardiac, thymic, and central nervous system structures. The malformations included microtia/anotia (15 infants), micrognathia (6), cleft palate (3), conotruncal heart defects and aortic-arch abnormalities (8), thymic defects (7), retinal or optic-nerve abnormalities (4), and central nervous system malformations (18). The pattern of malformation closely resembled that produced in animal studies of retinoid teratogenesis. It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations. (N Engl J Med 1985;313:837–41.)
Retinoic acids are analogues of vitamin A that display some of its biologic activities. Retinoic acids cannot replace the visual or reproductive functions of vitamin A, but they can assume its roles in stimulating bone growth and epithelial differentiation. Because of their effects on epithelial-cell differentiation and their relatively low toxicity as compared with vitamin A, retinoic acids were developed for the treatment of severe cystic acne and other chronic dermatoses.
1
,
2
The first of these retinoic acids, isotretinoin (13-
cis
-retinoic acid), was licensed in the United States in September 1982 with the brand name Accutane. According to marketing research . . .</description><subject>Abnormalities, Drug-Induced - etiology</subject><subject>Abortion</subject><subject>Abortion, Spontaneous - chemically induced</subject><subject>Acids</subject><subject>Acne</subject><subject>Acne Vulgaris - drug therapy</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Babies</subject><subject>Biological and medical sciences</subject><subject>Birth control</subject><subject>Birth defects</subject><subject>Case reports</subject><subject>Central nervous system</subject><subject>Children & youth</subject><subject>Cleft lip/palate</subject><subject>Disease control</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Female</subject><subject>Fetal Death - chemically induced</subject><subject>Fetuses</subject><subject>Heart</subject><subject>Heart Defects, Congenital - chemically induced</subject><subject>Heart diseases</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>Infants</subject><subject>Isotretinoin</subject><subject>Laboratory animals</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Microtia</subject><subject>Miscellaneous (drug allergy, mutagens, teratogens...)</subject><subject>Morphogenesis</subject><subject>Pediatrics</subject><subject>Pharmacology. Drug treatments</subject><subject>Pregnancy</subject><subject>Pregnancy Trimester, First</subject><subject>Prenatal exposure</subject><subject>Prospective Studies</subject><subject>Retina</subject><subject>Retinoic acid</subject><subject>Retrospective Studies</subject><subject>Risk</subject><subject>Rodents</subject><subject>Teratogenesis</subject><subject>Teratogenicity</subject><subject>Thymus</subject><subject>Tretinoin - adverse effects</subject><subject>Tretinoin - therapeutic use</subject><subject>Vitamin A</subject><subject>Womens health</subject><issn>0028-4793</issn><issn>1533-4406</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kM1Lw0AQxRdRaq3-ASJCQW8Sndmv7B5LqV9UBdHzstlsMKVJ6m56yH9vpKEncS5zmN97j3mEXCDcIgh597p4fkGtBAIwhgw54AEZo2As4RzkIRkDUJXwVLNjchLjCvpBrkdkxFBSBByT83fflnVTuunMlfl0UWWhaza2_epOyVFh19GfDXtCPu8XH_PHZPn28DSfLRPHhWgTp3OdWcZyxEJSRakShUu1ohwhz7QQ3EKaM1p4zgtMnQSrwUuRChSWiYxNyNXOdxOa762PrVk121D3kQZVqjjjmsqeYjvKhSbG4AuzCWVlQ2cQzG8b5o82etXl4L3NKp_vNcP7_f16uNvo7LoItnZl3GOKA5dIe-xmh1VVNLVfVf-G_gCcom8A</recordid><startdate>19851003</startdate><enddate>19851003</enddate><creator>Lammer, Edward J</creator><creator>Chen, Diane T</creator><creator>Hoar, Richard M</creator><creator>Agnish, Narsingh D</creator><creator>Benke, Paul J</creator><creator>Braun, John T</creator><creator>Curry, Cynthia J</creator><creator>Fernhoff, Paul M</creator><creator>Grix, Art W</creator><creator>Lott, Ira T</creator><creator>Richard, James M</creator><creator>Sun, Shyan C</creator><general>Massachusetts Medical Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0TZ</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K0Y</scope><scope>LK8</scope><scope>M0R</scope><scope>M0T</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope></search><sort><creationdate>19851003</creationdate><title>Retinoic Acid Embryopathy</title><author>Lammer, Edward J ; Chen, Diane T ; Hoar, Richard M ; Agnish, Narsingh D ; Benke, Paul J ; Braun, John T ; Curry, Cynthia J ; Fernhoff, Paul M ; Grix, Art W ; Lott, Ira T ; Richard, James M ; Sun, Shyan C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-c9d9ba33d11f6282285fc7982410db9554a07d32fe44f17c60a90e657515a35b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>Abnormalities, Drug-Induced - etiology</topic><topic>Abortion</topic><topic>Abortion, Spontaneous - chemically induced</topic><topic>Acids</topic><topic>Acne</topic><topic>Acne Vulgaris - drug therapy</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Babies</topic><topic>Biological and medical sciences</topic><topic>Birth control</topic><topic>Birth defects</topic><topic>Case reports</topic><topic>Central nervous system</topic><topic>Children & youth</topic><topic>Cleft lip/palate</topic><topic>Disease control</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Female</topic><topic>Fetal Death - chemically induced</topic><topic>Fetuses</topic><topic>Heart</topic><topic>Heart Defects, Congenital - chemically induced</topic><topic>Heart diseases</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>Infants</topic><topic>Isotretinoin</topic><topic>Laboratory animals</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Microtia</topic><topic>Miscellaneous (drug allergy, mutagens, teratogens...)</topic><topic>Morphogenesis</topic><topic>Pediatrics</topic><topic>Pharmacology. Drug treatments</topic><topic>Pregnancy</topic><topic>Pregnancy Trimester, First</topic><topic>Prenatal exposure</topic><topic>Prospective Studies</topic><topic>Retina</topic><topic>Retinoic acid</topic><topic>Retrospective Studies</topic><topic>Risk</topic><topic>Rodents</topic><topic>Teratogenesis</topic><topic>Teratogenicity</topic><topic>Thymus</topic><topic>Tretinoin - adverse effects</topic><topic>Tretinoin - therapeutic use</topic><topic>Vitamin A</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lammer, Edward J</creatorcontrib><creatorcontrib>Chen, Diane T</creatorcontrib><creatorcontrib>Hoar, Richard M</creatorcontrib><creatorcontrib>Agnish, Narsingh D</creatorcontrib><creatorcontrib>Benke, Paul J</creatorcontrib><creatorcontrib>Braun, John T</creatorcontrib><creatorcontrib>Curry, Cynthia J</creatorcontrib><creatorcontrib>Fernhoff, Paul M</creatorcontrib><creatorcontrib>Grix, Art W</creatorcontrib><creatorcontrib>Lott, Ira T</creatorcontrib><creatorcontrib>Richard, James M</creatorcontrib><creatorcontrib>Sun, Shyan C</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>New England Journal of Medicine</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><jtitle>The New England journal of medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lammer, Edward J</au><au>Chen, Diane T</au><au>Hoar, Richard M</au><au>Agnish, Narsingh D</au><au>Benke, Paul J</au><au>Braun, John T</au><au>Curry, Cynthia J</au><au>Fernhoff, Paul M</au><au>Grix, Art W</au><au>Lott, Ira T</au><au>Richard, James M</au><au>Sun, Shyan C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Retinoic Acid Embryopathy</atitle><jtitle>The New England journal of medicine</jtitle><addtitle>N Engl J Med</addtitle><date>1985-10-03</date><risdate>1985</risdate><volume>313</volume><issue>14</issue><spage>837</spage><epage>841</epage><pages>837-841</pages><issn>0028-4793</issn><eissn>1533-4406</eissn><coden>NEJMAG</coden><abstract>Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively. The outcomes in this cohort were 8 spontaneous abortions, 23 normal infants, and 5 malformed infants. Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5).
Among the 21 malformed infants we found a characteristic pattern of malformation involving craniofacial, cardiac, thymic, and central nervous system structures. The malformations included microtia/anotia (15 infants), micrognathia (6), cleft palate (3), conotruncal heart defects and aortic-arch abnormalities (8), thymic defects (7), retinal or optic-nerve abnormalities (4), and central nervous system malformations (18). The pattern of malformation closely resembled that produced in animal studies of retinoid teratogenesis. It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations. (N Engl J Med 1985;313:837–41.)
Retinoic acids are analogues of vitamin A that display some of its biologic activities. Retinoic acids cannot replace the visual or reproductive functions of vitamin A, but they can assume its roles in stimulating bone growth and epithelial differentiation. Because of their effects on epithelial-cell differentiation and their relatively low toxicity as compared with vitamin A, retinoic acids were developed for the treatment of severe cystic acne and other chronic dermatoses.
1
,
2
The first of these retinoic acids, isotretinoin (13-
cis
-retinoic acid), was licensed in the United States in September 1982 with the brand name Accutane. According to marketing research . . .</abstract><cop>Boston, MA</cop><pub>Massachusetts Medical Society</pub><pmid>3162101</pmid><doi>10.1056/NEJM198510033131401</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-4793 |
| ispartof | The New England journal of medicine, 1985-10, Vol.313 (14), p.837-841 |
| issn | 0028-4793 1533-4406 |
| language | eng |
| recordid | cdi_proquest_journals_1878434926 |
| source | MEDLINE; ProQuest Central UK/Ireland |
| subjects | Abnormalities, Drug-Induced - etiology Abortion Abortion, Spontaneous - chemically induced Acids Acne Acne Vulgaris - drug therapy Adolescent Adult Age Babies Biological and medical sciences Birth control Birth defects Case reports Central nervous system Children & youth Cleft lip/palate Disease control Drug toxicity and drugs side effects treatment Female Fetal Death - chemically induced Fetuses Heart Heart Defects, Congenital - chemically induced Heart diseases Hospitals Humans Infant, Newborn Infants Isotretinoin Laboratory animals Male Medical sciences Medicine Microtia Miscellaneous (drug allergy, mutagens, teratogens...) Morphogenesis Pediatrics Pharmacology. Drug treatments Pregnancy Pregnancy Trimester, First Prenatal exposure Prospective Studies Retina Retinoic acid Retrospective Studies Risk Rodents Teratogenesis Teratogenicity Thymus Tretinoin - adverse effects Tretinoin - therapeutic use Vitamin A Womens health |
| title | Retinoic Acid Embryopathy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-03T09%3A40%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Retinoic%20Acid%20Embryopathy&rft.jtitle=The%20New%20England%20journal%20of%20medicine&rft.au=Lammer,%20Edward%20J&rft.date=1985-10-03&rft.volume=313&rft.issue=14&rft.spage=837&rft.epage=841&rft.pages=837-841&rft.issn=0028-4793&rft.eissn=1533-4406&rft.coden=NEJMAG&rft_id=info:doi/10.1056/NEJM198510033131401&rft_dat=%3Cproquest_cross%3E4320952125%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1878434926&rft_id=info:pmid/3162101&rfr_iscdi=true |