Rachèl V. van Schendel|G. C. M. L. Page?Christiaens|Lean Beulen|C. M. Bilardo|Marjon A. de Boer|A. Coumans|Brigitte H. W. Faas|Irene M. van Langen|Klaske D. Lichtenbelt|Merel C. van Maarle|Merryn Macville|Dick Oepkes|Eva Pajkrt|Lidewij Henneman
Trial by Dutch laboratories for evaluation of non?invasive prenatal testing. Part II—women's perspectives
EMGO Institute for Health and Care Research|University Medical Center Utrecht|Radboud University Nijmegen|Radboud University Medical Center|University Medical Center Groningen|University of Groningen|Amsterdam UMC Location VUmc|Maastricht University Medical Centre|Radboud University Nijmegen|Radboud University Medical Center|University Medical Center Groningen|University of Groningen|University Medical Center Utrecht|Academic Medical Center|Maastricht University Medical Centre|Leiden University Medical Center|Academic Medical Center|EMGO Institute for Health and Care Research
prenatal diagnosisvolume 36 issue 12 p 10911098 original articleopen access trial dutch laboratories evaluation noninvasive prenatal testing part iiwomens perspectives rachl v van schendel rachl v van schendel department clinical genetics section community genetics emgo institute health care research vu university medical center amsterdam netherlandssearch papers authorg c lieve pagechristiaens g c lieve pagechristiaens department obstetrics gynaecology university medical center utrecht utrecht netherlandssearch papers authorlean beulen lean beulen department obstetrics gynaecology radboud university medical center nijmegen netherlandssearch papers authorcatia bilardo catia bilardo department obstetrics gynaecology university medical center groningen university groningen groningen netherlandssearch papers authormarjon de boer marjon de boer department obstetrics gynaecology vu university medical center amsterdam netherlandssearch papers authoraudrey b c coumans audrey b c coumans department obstetrics gynaecology maastricht umc maastricht netherlandssearch papers authorbrigitte h faas brigitte h faas department human genetics radboud university medical center nijmegen netherlandssearch papers authorirene van langen irene van langen department genetics university medical center groningen university groningen groningen netherlandssearch papers authorklaske lichtenbelt klaske lichtenbelt department medical genetics university medical center utrecht utrecht netherlandssearch papers authormerel c van maarle merel c van maarle department clinical genetics academic medical center amsterdam netherlandssearch papers authormerryn v e macville merryn v e macville department clinical genetics maastricht umc maastricht netherlandssearch papers authordick oepkes dick oepkes department obstetrics leiden university medical center leiden netherlandssearch papers authoreva pajkrt eva pajkrt department obstetrics gynaecology academic medical centre amsterdam netherlandssearch papers authorlidewij henneman corresponding author lidewij henneman lhennemanvumcnl department clinical genetics section community genetics emgo institute health care research vu university medical center amsterdam netherlandscorrespondence lidewij henneman email lhennemanvumcnlsearch papers authorfor dutch nipt consortium dutch nipt consortiumsearch papers author rachl v van schendel rachl v van schendel department clinical genetics section community genetics emgo institute health care research vu university medical center amsterdam netherlandssearch papers authorg c lieve pagechristiaens g c lieve pagechristiaens department obstetrics gynaecology university medical center utrecht utrecht netherlandssearch papers authorlean beulen lean beulen department obstetrics gynaecology radboud university medical center nijmegen netherlandssearch papers authorcatia bilardo catia bilardo department obstetrics gynaecology university medical center groningen university groningen groningen netherlandssearch papers authormarjon de boer marjon de boer department obstetrics gynaecology vu university medical center amsterdam netherlandssearch papers authoraudrey b c coumans audrey b c coumans department obstetrics gynaecology maastricht umc maastricht netherlandssearch papers authorbrigitte h faas brigitte h faas department human genetics radboud university medical center nijmegen netherlandssearch papers authorirene van langen irene van langen department genetics university medical center groningen university groningen groningen netherlandssearch papers authorklaske lichtenbelt klaske lichtenbelt department medical genetics university medical center utrecht utrecht netherlandssearch papers authormerel c van maarle merel c van maarle department clinical genetics academic medical center amsterdam netherlandssearch papers authormerryn v e macville merryn v e macville department clinical genetics maastricht umc maastricht netherlandssearch papers authordick oepkes dick oepkes department obstetrics leiden university medical center leiden netherlandssearch papers authoreva pajkrt eva pajkrt department obstetrics gynaecology academic medical centre amsterdam netherlandssearch papers authorlidewij henneman corresponding author lidewij henneman lhennemanvumcnl department clinical genetics section community genetics emgo institute health care research vu university medical center amsterdam netherlandscorrespondence lidewij henneman email lhennemanvumcnlsearch papers authorfor dutch nipt consortium dutch nipt consortiumsearch papers author first published 14 october 2016 httpsdoiorg101002pd4941citations 46 part paper presented 19th international conference prenatal diagnosis therapy 2015 european human genetics conference 2015 funding sources supported grant netherlands organisation health research development zonmw 200340002 conflicts interest since 18 january 2016 dr pagechristiaens employed associated medical director illumina inc dr oepkes previously participated clinical research sponsored ariosa diagnostics natera inc aboutsectionspdf toolsrequest permissionexport citationadd favoritestrack citation shareshare give accessshare full text accessshare fulltext accessplease review terms conditions use check box share fulltext version articlei read accept wiley online library terms conditions useshareable linkuse link share fulltext version article friends colleagues learn morecopy url share linkshare onfacebooktwitterlinkedinredditwechat abstract objective evaluate preferences decisionmaking among highrisk pregnant women offered choice noninvasive prenatal testing nipt invasive testing testing methods nationwide implementation study trident offering nipt contingent screening test women increased risk fetal aneuploidy based firsttrimester combined testing 1200 medical history questionnaire completed counseling assessing knowledge attitudes participation following multidimensional measure informed choice results total 10911253 87 women completed questionnaire 1053 965 underwent nipt 37 34 invasive testing 1 01 declined testing 917 preferred nipt test safety overall 779 made informed choice 898 sufficient knowledge 905 positive attitudes towards nipt women intermediate odds ratio 351170722 p 0001 high educational level 436222854 p 0001 women adequate health literacy 260136495 p 0004 likely make informed choice informed choice associated less decisional conflict less anxiety p 0001 intention terminate pregnancy syndrome higher among women undergoing invasive testing 865 compared undergoing nipt 584 p 0001 conclusions majority women sufficient knowledge made informed choice continuous attention counseling required especially loweducated less healthliterate women 2016 authors prenatal diagnosis published john wiley sons ltd introduction noninvasive prenatal testing nipt fetal aneuploidy changed landscape prenatal screening worldwide1 nipt uses sequencing cellfree dna cfdna maternal plasma screen trisomy 21 18 13 high accuracy high lowrisk populations2 3 women elevated risk based firsttrimester sequential screening nipt considered good followup test prevents need invasive testing thereby avoiding risk iatrogenic loss pregnancy4 invasive test confirmation however still necessary potential falsepositive nipt results although advantages offered nipt created strong demand implement test concerns raised regarding potential impact informed decisionmaking5 pregnant women health professionals expressed fears nipt might become routinized women might feel pressured accept it68 could potentially undermine aim prenatal screening enable pregnant women make autonomous reproductive choice9 informed choice commonly defined decision made sufficient knowledge consistent decisionmakers values behaviorally implemented10 ability make informed choice shown associated beneficial psychological outcomes less decisional conflict regarding choice11 12 safeguard process informed decisionmaking need comprehensive counseling nipt emphasized9 13 1 april 2014 netherlands incorporated nipt governmentally supported healthcarefunded fetal trisomy screening program realized nationwide implementation study trident study trial dutch laboratories evaluation noninvasive prenatal testing nipt offered additional choice women elevated risk fetal trisomy 21 18 13 based firsttrimester combined testing fct based medical history netherlands around 27 pregnant women decide fct14 trident study two main objectives first evaluate clinical impact uptake test performance turnaroundtime pregnancy outcome results reported separately oepkes et al15 paper part second part report womens preferences decisionmaking informed choice decisional conflict anxiety methods trident study women increased risk fetal trisomy referred indepth counseling one eight dutch regional prenatal diagnosis centers satellite centers n 13 pregnant women offered choice nipt invasive testing chorionic villus sampling cvs amniocentesis ac testing details trident study found separate paper part oepkes et al15 seven eight centers women participating trident study first five months 1 april 1 september 2014 asked fill two questionnaires approval study granted dutch government population screening act license 350010118701pg local university medical ethics committees participants pregnant women increased risk fetal trisomy 21 18 13 based results firsttrimester combined test cutoff risk 1200 based medical history ie prior pregnancy fetal trisomy 13 18 21 parental balanced robertsonian translocation increased risk t21 t13 considered eligible exclusion criteria gestational age 10 0 weeks 18 years old inability provide informed consent multiple pregnancies vanishing twin nuchal translucency 35 mm structural fetal anomalies maternal history malignancy known maternal chromosomal abnormality participants received unique trident study number information counseling standard pretest counseling nipt discussed alternative option invasive testing case fct result indicating elevated risk women given oral counseling obstetricians maternal fetal medicine specialists specially trained counselors women also given written information nipt invasive diagnostic testing cvs ac following topics addressed test procedure including risk invasive testing reporting time test sensitivity t21 18 13 meaning abnormal test result necessity confirm abnormal nipt results invasive testing furthermore dedicated website dutch launched wwwmeeroverniptnl women could find additional information ask questions nipt trident study procedure two questionnaires designed multidisciplinary team social scientists psychologists obstetricians clinical geneticist women asked fill first questionnaire q1 directly counseling done either paper six centers online one center counselors three centers however asked women choosing nipt choosing invasive testing fill questionnaire overall number women electing invasive testing low study mostly reflects findings women choosing nipt second questionnaire q2 completed women received test results responses first questionnaire q1 presented measures q1 registered indication followup testing abnormal fct medical history whether women would fct nipt available next women asked indicate list options important reason preferring either nipt invasive testing testing informed choice measured using modified multidimensional measure informed choice mmic developed marteau et al10 11 method comprises dimensions knowledge attitude uptake measure adapted reflect test options current study womens knowledge nipt measured 5item scale designed study supplementary table s1 questions covered information nipts characteristics implications testing discussed information leaflet counseling womens knowledge invasive testing assessed except one question addressed accuracy nipt compared invasive testing womens attitudes towards nipt invasive testing measured using semantic differential 5point scale four bipolar adjective pairs based van den berg et al12 negativepositive difficulteasy frighteningnotfrightening reassuringnotreassuring terms reliability nipt attitude scale invasive testing attitude scale internally consistent cronbachs alpha 079 085 respectively type test women decided anonymously assessed trident study laboratory database using trident study number extent women accepted fact nipt give 100 certainty fact invasive testing miscarriage risk measured 5point scale compressed 3point scale acceptable neutral acceptable analysis womens attitude towards termination pregnancy case syndrome trisomy 13 18 measured single item 5point scale compressed 3point scale probably maybemaybe probably difficulties decisionmaking decisional conflict assessed dutch version 16item decisional conflict scale dcs developed oconnor16 translated validated koedoot et al17 cronbachs alpha dcs 097 state anxiety measured dutch version sixitem short form state scale spielberger statetrait anxiety inventory stai18 19 cronbachs alpha 087 health literacy measured dutch version chews set brief screening questions20 translated adapted fransen et al21 cronbachs alpha 068 following sociodemographic variables assessed age parity level education ethnicity religion level religiousness activesomewhat active activenot religious women asked indicate gestational age whether conceived naturally via assisted reproductive technology art data analysis descriptive analyses used describe womens characteristics mmic analysis knowledge sumscores dichotomized sufficient insufficient knowledge standard criteria sufficient insufficient knowledge available decided cutoff 25 questions would constitute sufficient knowledge questionnaires women left two knowledge questions blank excluded analyses woman left one two questions blank checked box dont know treated incorrect answers attitude scores categorized positive neutral negative people neutral attitude cannot classified either positive negative attitude towards nipt excluded analysis proposed van den berg et al12 considered better approach original application dichotomization mmic attitude scale22 attitude combined nipt uptake assess valueconsistency women chose nipt positive attitude women declined nipt negative attitude classified valueconsistent nipt acceptors negative attitude nipt decliners positive attitude classified valueinconsistent based knowledge valueconsistency assessed whether women made informed choice woman sufficient knowledge classified valueconsistent informed choice made10 11 womens knowledge insufficient andor classified valueinconsistent choice considered uninformed differences women chose nipt women chose invasive testing evaluated using fishers exact test evaluate variables associated making informed choice univariate multiple logistic regression used statistical significance set p 01 p 005 respectively mannwhitney test used nonnormality items determine differences decisional conflict anxiety women making informed uninformed choice analyses performed using spss version 20 windows ibm statistics windows ibm ny usa results womens characteristics total 10911253 pregnant women filled q1 87 response womens characteristics presented table 1 615 women highly educated 749 dutch origin mean age 359 years range 2145 mean gestational age 140 weeks range 934 majority women 86 offered nipt high risk 1200 fct 14 medical history table 1 characteristics participants n 1091 characteristics n maternal age missing 7 25 2635 36 24 22 424 391 636 587 level educationa missing 2 low intermediate high 92 84 327 300 670 615 ethnicityb missing14 dutch western nonwestern 807 749 129 120 141 131 religionc missing 5 none christian muslim hindu 679 625 321 296 42 39 14 13 30 28 level religiousness missing 10 somewhat active activenot religious 205 190 876 810 health literacyd missing 3 inadequate adequate 93 85 995 915 parity missing 12 0 1 407 377 672 623 method conception missing 33 natural via assisted reproductive technologye 903 828 155 142 gestational age weeks missing 14 924 25 1067 991 10 09 indication followup testing missing 4 fct risk 1200 medical historyf 935 860 152 140 fct risk fetal trisomy na 152 110 1111200 unknown 50 53 785 837 104 110 fct firsttrimester combined test na applicable numbers may add total missing values low elementary school lower level secondary school lower vocational training medium higher level secondary school intermediate vocational training high high vocational training university23 b ethnicity categorized dutch western nonwestern following algorithm dutch parents born netherlands western least one parents born europe excluding turkey north america oceania indonesia japan nonwestern least one parents born africa latin america asia excluding indonesia japan turkey parents born abroad country mother23 c christian calvinism protestantism roman catholic reformed baptism example jewish buddhist jehovahs witness inadequate health literacy answered never occasionally one items based chew et al20 e intrauterine insemination iui n 47 vitro fertilization ivf n 38 intracytoplasmic sperm injection icsi n 26 preimplantation genetic diagnosis pgd n 14 ovulation induction n 12 n 18 f previous child trisomy 21 18 13 n 114 disorder n 17 ultrasound anomaly n 9 pregnant intracytoplasmic sperm injection isci n 7 parental robertsonian translocation n 5 informed choice analysis using mmic 52 questionnaires excluded missing data attitude questions women neutral attitude n 367 excluded analysis reasons mentioned seven women left two knowledge questions blank excluded analysis resulting total sample 665 participants used informed choice analysis test preference sample 1091 women 1053 965 nipt 37 women 34 invasive testing one woman 01 declined testing main reason preferring nipt safety 917 table 2 almost half women preferred invasive testing test accuracy 471 353 faster test results woman refrained testing avoid anxiety table 2 reasons preferring nipt invasive testing testing test choice reason n nipt n 1053 missing 55 safe baby doctor advised nipt done early pregnancy easy partner wanted reasons 915 917 28 28 21 21 17 17 2 02 15 15 invasive testing n 37 missing 3 test accuracy faster test results gives information unborn child doctor advised invasive testing reasons 16 471 12 353 3 88 1 29 2 59 testing n 1 followup testing gives anxiety 1 100 women invasive testing significantly often high priori risk 110 compared women nipt p 0001 significant difference age level education parity medical history conception via art women chose invasive testing women chose nipt majority women 77 undergoing nipt found acceptable nipt give 100 certainty 27 women undergoing invasive testing found acceptable p 0001 contrast fact invasive testing associated increased risk miscarriage acceptable 73 women undergoing invasive testing 159 women nipt p 0001 table s2 intentions case abnormal result intention terminate pregnancy syndrome higher among women invasive testing 865 compared nipt 584 p 0001 also case trisomy 13 18 although less pronounced 946 vs 776 respectively p 0013 table s2 informed choice shown table 3 898 women sufficient knowledge nipt 905 positive attitude towards nipt 863 made decision valueconsistent women intermediate higher education likely sufficient knowledge nipt lower level education p 0001 significant difference knowledge women nipt women invasive testing answers separate knowledge questions presented supplementary table s2 table 3 description characteristics informed choice measures measure description items reliability range mean sd cutoff outcome knowledge score knowledge characteristics nipt meaning test results five correctincorrect items 05 40 11 2 sufficient knowledge 898 attitude scale attitude towards nipt four 5point items 079 420 167 35 14 positivea 10 negativea positive attitude 905 negative attitude 95 test uptake whether woman nipt based laboratory records test uptake 965 valueconsistency consistency value attitude behavior test uptake calculatedb valueconsistent 863 informed choice knowledgeable valueconsistent decision calculatedc informed choice 779 sd standard deviation attitudes divided three equal categories neutral attitudes middle category n 367 excluded analysis12 b women positive attitude towards nipt chose nipt women negative attitude chose nipt classified valueconsistent c informed choice made woman sufficient knowledge made valueconsistent decision cases decision labeled uninformed informed choice analysis showed 779 women made informed choice nipt made uninformed choice 221 insufficient knowledge 84 valueinconsistency 117 insufficient knowledge valueinconsistent decision 2 table 4 women invasive testing positive attitude towards nipt therefore based criteria mmic scored made valueinconsistent choice however data showed 786 women also positive attitude towards invasive testing choice invasive testing valueconsistent thus probably uninformed could calculated womens knowledge invasive testing measured women invasive testing excluded analysis percentage informed choice 81 significant difference informed choice women offered testing highrisk fct results high risk based medical history also difference rates informed choice seven participating centers table 4 types informed uninformed choice n 665a knowledge attitude uptake n informed choice good good positive negative yes 518 0 779 0 uninformed choice good good poor poor poor poor positive negative positive negative positive negative yes yes yes 22 56 56 0 6 7 33 84 84 0 09 11 typology based marteau et al10 women neutral attitudes n 367 excluded analysis based van den berg et al12 shown table 5 univariate analysis revealed women making informed choice significantly likely 36 years old intermediate higher education low level religiousness adequate health literacy heard nipt participating study women nonwestern ethnicity significantly less likely make informed choice multivariate analysis showed women intermediate odds ratio 351 95confidence interval ci 170722 p 0001 high level education 436 95ci 222854 p 0001 adequate health literacy 260 95ci 136495 p 0004 significantly likely make informed decision table 5 univariate multiple logistic regression factors associated making informed choice variable univariate logistic regression informed choice n 665 multiple logistic regression informed choice n 581a odds ratio 95ci pvalueb odds ratio 95ci pvaluec age 25 2635 36 285 429 0801016 1211521 0014 0106 0024 150 225 035641 053958 0113 0592 0275 level education low intermediate high 410 456 211798 246844 0001 0001 0001 351 436 170722 222854 0