Effects of medication intake in early pregnancy on the fetal fraction of cell‐free DNA testing
Objectives To determine the association between medications intake in early pregnancy and variation in the fetal fraction (FF) in pregnant women undergoing cell‐free DNA (cfDNA) testing. Methods We performed a retrospective cohort study of women (n = 1051) undergoing cfDNA testing at an academic cen...
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| Veröffentlicht in: | Prenatal diagnosis 2019-04, Vol.39 (5), p.361-368 |
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| creator | Kuhlmann‐Capek, Maggie Chiossi, Giuseppe Singh, Prapti Monsivais, Luis Lozovyy, Violetta Gallagher, Lauren Kirsch, Nathan Florence, Elizabeth Petruzzi, Victoria Chang, Jeffrey Buenaventura, Sofia Walden, Paul Gardner, Benjamin Munn, Mary Costantine, Maged |
| description | Objectives
To determine the association between medications intake in early pregnancy and variation in the fetal fraction (FF) in pregnant women undergoing cell‐free DNA (cfDNA) testing.
Methods
We performed a retrospective cohort study of women (n = 1051) undergoing cfDNA testing at an academic center. The exposed group included women taking medications (n = 400; 38.1%), while the nonexposed group consisted of women taking no medications (n = 651; 61.9%). Our primary outcome was FF. We performed univariate and multivariate analyses as appropriate.
Results
The FFs were 8.8% (6.6‐12.1), 8.7% (6.3‐11.6), and 7.7% (5.1‐9.3) among women taking 0, 1, and two or more medications, respectively (P |
| doi_str_mv | 10.1002/pd.5436 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2186618264</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2214955038</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3456-9e45fd8ee6f22b3ea38326a577da42586e679d48677b9c1a3c606fcaf3b26163</originalsourceid><addsrcrecordid>eNp1kNtKw0AQhhdRbK3iG8iCFwqSuodkk1yWth6gqBe9Xzeb2ZqaJnE3RXrnI_iMPonbg14IwsAMzDf_P_wInVLSp4Sw6ybvRyEXe6hLSRoHhDG-j7qE-pknEe2gI-fmHkxYGh-iDidx6It30fPYGNCtw7XBC8gLrdqirnBRteoVfMOgbLnCjYVZpSq9wn7ZvgA20KoSG6v0hvfXGsry6-PTWAA8ehjgFlxbVLNjdGBU6eBk13toejOeDu-CyePt_XAwCTQPIxGkEEYmTwCEYSzjoHjCmVBRHOcqZFEiQMRpHiYijrNUU8W1IMJoZXjGBBW8hy63so2t35beWi4Kt35JVVAvnWQ0EYImTIQePf-DzuulrfxzkjEaplFEvHkPXWwpbWvnLBjZ2GKh7EpSIteZyyaX68w9ebbTW2Y-wl_uJ2QPXG2B96KE1X868mm0kfsGz4mI-w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2214955038</pqid></control><display><type>article</type><title>Effects of medication intake in early pregnancy on the fetal fraction of cell‐free DNA testing</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Kuhlmann‐Capek, Maggie ; Chiossi, Giuseppe ; Singh, Prapti ; Monsivais, Luis ; Lozovyy, Violetta ; Gallagher, Lauren ; Kirsch, Nathan ; Florence, Elizabeth ; Petruzzi, Victoria ; Chang, Jeffrey ; Buenaventura, Sofia ; Walden, Paul ; Gardner, Benjamin ; Munn, Mary ; Costantine, Maged</creator><creatorcontrib>Kuhlmann‐Capek, Maggie ; Chiossi, Giuseppe ; Singh, Prapti ; Monsivais, Luis ; Lozovyy, Violetta ; Gallagher, Lauren ; Kirsch, Nathan ; Florence, Elizabeth ; Petruzzi, Victoria ; Chang, Jeffrey ; Buenaventura, Sofia ; Walden, Paul ; Gardner, Benjamin ; Munn, Mary ; Costantine, Maged</creatorcontrib><description>Objectives
To determine the association between medications intake in early pregnancy and variation in the fetal fraction (FF) in pregnant women undergoing cell‐free DNA (cfDNA) testing.
Methods
We performed a retrospective cohort study of women (n = 1051) undergoing cfDNA testing at an academic center. The exposed group included women taking medications (n = 400; 38.1%), while the nonexposed group consisted of women taking no medications (n = 651; 61.9%). Our primary outcome was FF. We performed univariate and multivariate analyses as appropriate.
Results
The FFs were 8.8% (6.6‐12.1), 8.7% (6.3‐11.6), and 7.7% (5.1‐9.3) among women taking 0, 1, and two or more medications, respectively (P < 0.01). Using multivariable linear mixed effects model, the mean FF was significantly lower among those taking two or more medications compared with the nonexposed group. FF was directly correlated with gestational age at the time of cfDNA testing and inversely correlated with maternal obesity. Exposure to metformin was associated with 1.8% (0.2‐3.4) lower mean FF when compared with the nonexposed group (P = 0.02). Obesity and intake of two or more medications were associated with higher hazard ratio of having a low FF less than 4%.
Conclusions
Exposure to metformin or two or more medications was associated with decreased FF, and obesity is associated with delay in achieving adequate FF percentage. These findings should be considered while counseling patients on test limitations.
What is already known about this topic?
Several factors have been reported to affect the fetal fraction of cell‐free DNA noninvasive prenatal testing. While there are reports that heparin may affect the fetal fraction and may lead to false‐negative results for Down syndrome, there are sparse data from larger studies on the effect of medications intake in pregnancy on fetal fraction.
What does this study add?
This study investigates heparin, as well as other commonly used classes of medications, in regard to their effect on fetal fraction at the time of noninvasive prenatal testing. We report that metformin may have a significant effect on the fetal fraction. We also confirm previous findings regarding the effects of obesity and gestational age at testing on fetal fraction.</description><identifier>ISSN: 0197-3851</identifier><identifier>EISSN: 1097-0223</identifier><identifier>DOI: 10.1002/pd.5436</identifier><identifier>PMID: 30740743</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adult ; Cell-Free Nucleic Acids - drug effects ; Deoxyribonucleic acid ; DNA ; DNA testing ; Exposure ; Female ; Fetuses ; Gestational age ; Humans ; Hypoglycemic Agents - adverse effects ; Metformin ; Metformin - adverse effects ; Noninvasive Prenatal Testing ; Obesity ; Pregnancy ; Retrospective Studies</subject><ispartof>Prenatal diagnosis, 2019-04, Vol.39 (5), p.361-368</ispartof><rights>2019 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3456-9e45fd8ee6f22b3ea38326a577da42586e679d48677b9c1a3c606fcaf3b26163</citedby><cites>FETCH-LOGICAL-c3456-9e45fd8ee6f22b3ea38326a577da42586e679d48677b9c1a3c606fcaf3b26163</cites><orcidid>0000-0002-7632-121X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpd.5436$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpd.5436$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30740743$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuhlmann‐Capek, Maggie</creatorcontrib><creatorcontrib>Chiossi, Giuseppe</creatorcontrib><creatorcontrib>Singh, Prapti</creatorcontrib><creatorcontrib>Monsivais, Luis</creatorcontrib><creatorcontrib>Lozovyy, Violetta</creatorcontrib><creatorcontrib>Gallagher, Lauren</creatorcontrib><creatorcontrib>Kirsch, Nathan</creatorcontrib><creatorcontrib>Florence, Elizabeth</creatorcontrib><creatorcontrib>Petruzzi, Victoria</creatorcontrib><creatorcontrib>Chang, Jeffrey</creatorcontrib><creatorcontrib>Buenaventura, Sofia</creatorcontrib><creatorcontrib>Walden, Paul</creatorcontrib><creatorcontrib>Gardner, Benjamin</creatorcontrib><creatorcontrib>Munn, Mary</creatorcontrib><creatorcontrib>Costantine, Maged</creatorcontrib><title>Effects of medication intake in early pregnancy on the fetal fraction of cell‐free DNA testing</title><title>Prenatal diagnosis</title><addtitle>Prenat Diagn</addtitle><description>Objectives
To determine the association between medications intake in early pregnancy and variation in the fetal fraction (FF) in pregnant women undergoing cell‐free DNA (cfDNA) testing.
Methods
We performed a retrospective cohort study of women (n = 1051) undergoing cfDNA testing at an academic center. The exposed group included women taking medications (n = 400; 38.1%), while the nonexposed group consisted of women taking no medications (n = 651; 61.9%). Our primary outcome was FF. We performed univariate and multivariate analyses as appropriate.
Results
The FFs were 8.8% (6.6‐12.1), 8.7% (6.3‐11.6), and 7.7% (5.1‐9.3) among women taking 0, 1, and two or more medications, respectively (P < 0.01). Using multivariable linear mixed effects model, the mean FF was significantly lower among those taking two or more medications compared with the nonexposed group. FF was directly correlated with gestational age at the time of cfDNA testing and inversely correlated with maternal obesity. Exposure to metformin was associated with 1.8% (0.2‐3.4) lower mean FF when compared with the nonexposed group (P = 0.02). Obesity and intake of two or more medications were associated with higher hazard ratio of having a low FF less than 4%.
Conclusions
Exposure to metformin or two or more medications was associated with decreased FF, and obesity is associated with delay in achieving adequate FF percentage. These findings should be considered while counseling patients on test limitations.
What is already known about this topic?
Several factors have been reported to affect the fetal fraction of cell‐free DNA noninvasive prenatal testing. While there are reports that heparin may affect the fetal fraction and may lead to false‐negative results for Down syndrome, there are sparse data from larger studies on the effect of medications intake in pregnancy on fetal fraction.
What does this study add?
This study investigates heparin, as well as other commonly used classes of medications, in regard to their effect on fetal fraction at the time of noninvasive prenatal testing. We report that metformin may have a significant effect on the fetal fraction. We also confirm previous findings regarding the effects of obesity and gestational age at testing on fetal fraction.</description><subject>Adult</subject><subject>Cell-Free Nucleic Acids - drug effects</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA testing</subject><subject>Exposure</subject><subject>Female</subject><subject>Fetuses</subject><subject>Gestational age</subject><subject>Humans</subject><subject>Hypoglycemic Agents - adverse effects</subject><subject>Metformin</subject><subject>Metformin - adverse effects</subject><subject>Noninvasive Prenatal Testing</subject><subject>Obesity</subject><subject>Pregnancy</subject><subject>Retrospective Studies</subject><issn>0197-3851</issn><issn>1097-0223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kNtKw0AQhhdRbK3iG8iCFwqSuodkk1yWth6gqBe9Xzeb2ZqaJnE3RXrnI_iMPonbg14IwsAMzDf_P_wInVLSp4Sw6ybvRyEXe6hLSRoHhDG-j7qE-pknEe2gI-fmHkxYGh-iDidx6It30fPYGNCtw7XBC8gLrdqirnBRteoVfMOgbLnCjYVZpSq9wn7ZvgA20KoSG6v0hvfXGsry6-PTWAA8ehjgFlxbVLNjdGBU6eBk13toejOeDu-CyePt_XAwCTQPIxGkEEYmTwCEYSzjoHjCmVBRHOcqZFEiQMRpHiYijrNUU8W1IMJoZXjGBBW8hy63so2t35beWi4Kt35JVVAvnWQ0EYImTIQePf-DzuulrfxzkjEaplFEvHkPXWwpbWvnLBjZ2GKh7EpSIteZyyaX68w9ebbTW2Y-wl_uJ2QPXG2B96KE1X868mm0kfsGz4mI-w</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>Kuhlmann‐Capek, Maggie</creator><creator>Chiossi, Giuseppe</creator><creator>Singh, Prapti</creator><creator>Monsivais, Luis</creator><creator>Lozovyy, Violetta</creator><creator>Gallagher, Lauren</creator><creator>Kirsch, Nathan</creator><creator>Florence, Elizabeth</creator><creator>Petruzzi, Victoria</creator><creator>Chang, Jeffrey</creator><creator>Buenaventura, Sofia</creator><creator>Walden, Paul</creator><creator>Gardner, Benjamin</creator><creator>Munn, Mary</creator><creator>Costantine, Maged</creator><general>Wiley Subscription Services, Inc</general><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>7QP</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7632-121X</orcidid></search><sort><creationdate>201904</creationdate><title>Effects of medication intake in early pregnancy on the fetal fraction of cell‐free DNA testing</title><author>Kuhlmann‐Capek, Maggie ; Chiossi, Giuseppe ; Singh, Prapti ; Monsivais, Luis ; Lozovyy, Violetta ; Gallagher, Lauren ; Kirsch, Nathan ; Florence, Elizabeth ; Petruzzi, Victoria ; Chang, Jeffrey ; Buenaventura, Sofia ; Walden, Paul ; Gardner, Benjamin ; Munn, Mary ; Costantine, Maged</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3456-9e45fd8ee6f22b3ea38326a577da42586e679d48677b9c1a3c606fcaf3b26163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Cell-Free Nucleic Acids - drug effects</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA testing</topic><topic>Exposure</topic><topic>Female</topic><topic>Fetuses</topic><topic>Gestational age</topic><topic>Humans</topic><topic>Hypoglycemic Agents - adverse effects</topic><topic>Metformin</topic><topic>Metformin - adverse effects</topic><topic>Noninvasive Prenatal Testing</topic><topic>Obesity</topic><topic>Pregnancy</topic><topic>Retrospective Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuhlmann‐Capek, Maggie</creatorcontrib><creatorcontrib>Chiossi, Giuseppe</creatorcontrib><creatorcontrib>Singh, Prapti</creatorcontrib><creatorcontrib>Monsivais, Luis</creatorcontrib><creatorcontrib>Lozovyy, Violetta</creatorcontrib><creatorcontrib>Gallagher, Lauren</creatorcontrib><creatorcontrib>Kirsch, Nathan</creatorcontrib><creatorcontrib>Florence, Elizabeth</creatorcontrib><creatorcontrib>Petruzzi, Victoria</creatorcontrib><creatorcontrib>Chang, Jeffrey</creatorcontrib><creatorcontrib>Buenaventura, Sofia</creatorcontrib><creatorcontrib>Walden, Paul</creatorcontrib><creatorcontrib>Gardner, Benjamin</creatorcontrib><creatorcontrib>Munn, Mary</creatorcontrib><creatorcontrib>Costantine, Maged</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Prenatal diagnosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuhlmann‐Capek, Maggie</au><au>Chiossi, Giuseppe</au><au>Singh, Prapti</au><au>Monsivais, Luis</au><au>Lozovyy, Violetta</au><au>Gallagher, Lauren</au><au>Kirsch, Nathan</au><au>Florence, Elizabeth</au><au>Petruzzi, Victoria</au><au>Chang, Jeffrey</au><au>Buenaventura, Sofia</au><au>Walden, Paul</au><au>Gardner, Benjamin</au><au>Munn, Mary</au><au>Costantine, Maged</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of medication intake in early pregnancy on the fetal fraction of cell‐free DNA testing</atitle><jtitle>Prenatal diagnosis</jtitle><addtitle>Prenat Diagn</addtitle><date>2019-04</date><risdate>2019</risdate><volume>39</volume><issue>5</issue><spage>361</spage><epage>368</epage><pages>361-368</pages><issn>0197-3851</issn><eissn>1097-0223</eissn><abstract>Objectives
To determine the association between medications intake in early pregnancy and variation in the fetal fraction (FF) in pregnant women undergoing cell‐free DNA (cfDNA) testing.
Methods
We performed a retrospective cohort study of women (n = 1051) undergoing cfDNA testing at an academic center. The exposed group included women taking medications (n = 400; 38.1%), while the nonexposed group consisted of women taking no medications (n = 651; 61.9%). Our primary outcome was FF. We performed univariate and multivariate analyses as appropriate.
Results
The FFs were 8.8% (6.6‐12.1), 8.7% (6.3‐11.6), and 7.7% (5.1‐9.3) among women taking 0, 1, and two or more medications, respectively (P < 0.01). Using multivariable linear mixed effects model, the mean FF was significantly lower among those taking two or more medications compared with the nonexposed group. FF was directly correlated with gestational age at the time of cfDNA testing and inversely correlated with maternal obesity. Exposure to metformin was associated with 1.8% (0.2‐3.4) lower mean FF when compared with the nonexposed group (P = 0.02). Obesity and intake of two or more medications were associated with higher hazard ratio of having a low FF less than 4%.
Conclusions
Exposure to metformin or two or more medications was associated with decreased FF, and obesity is associated with delay in achieving adequate FF percentage. These findings should be considered while counseling patients on test limitations.
What is already known about this topic?
Several factors have been reported to affect the fetal fraction of cell‐free DNA noninvasive prenatal testing. While there are reports that heparin may affect the fetal fraction and may lead to false‐negative results for Down syndrome, there are sparse data from larger studies on the effect of medications intake in pregnancy on fetal fraction.
What does this study add?
This study investigates heparin, as well as other commonly used classes of medications, in regard to their effect on fetal fraction at the time of noninvasive prenatal testing. We report that metformin may have a significant effect on the fetal fraction. We also confirm previous findings regarding the effects of obesity and gestational age at testing on fetal fraction.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30740743</pmid><doi>10.1002/pd.5436</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-7632-121X</orcidid></addata></record> |
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| source | MEDLINE; Access via Wiley Online Library |
| subjects | Adult Cell-Free Nucleic Acids - drug effects Deoxyribonucleic acid DNA DNA testing Exposure Female Fetuses Gestational age Humans Hypoglycemic Agents - adverse effects Metformin Metformin - adverse effects Noninvasive Prenatal Testing Obesity Pregnancy Retrospective Studies |
| title | Effects of medication intake in early pregnancy on the fetal fraction of cell‐free DNA testing |
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