Influence of Prenatal Counseling on the Attitudes and Preferences Towards Invasive Prenatal Testing Among Women in Their First Trimester of Pregnancy
Phase: NA
Conditions: Genetic Counseling, Prenatal Diagnosis
Sponsor: Hospital Clinic of Barcelona

 
 
 
 
PROTOCOL FOR A RANDOMIZED CONTROLLED TRIAL 
 
Raigam J. Martinez-Portilla 
Fernanda Paz y Miño 
Montse Pauta 
Antoni Borrell 
 
Hospital Clinic of Barcelona / University of Barcelona 
 
 
Study Number: IRN2019/03/0001 
Human Subjects Review Approval: HCB/2019/0788 
 
 
September 15th, 2019 

 
Study design: 
This is a randomized open-label controlled trial evaluating the impact of an extra 15-minute prenatal 
counseling before the first trimester combined screening test for Down’s syndrome, on the women’s 
attitudes and preferences towards having an invasive testing as the first line option for screening of 
chromosomal abnormalities. 
 
Data will be collected by the study-site manager and stored in an electronic data-capture database. The 
coordinator of the study and the statistician will witness the accuracy of the data at the beginning, middle, 
and end of the study (on-site audit). Data will be captured in a paper form basis and then captured into the 
electronic database.  
 
Participants 
Inclusion criteria:  any pregnant woman of at least 18 years old, attending the first trimester combined 
screening test for chromosomal abnormalities (between 11+0 and 13+6 weeks’ gestation). The exclusion 
criteria: women not willing to participate in the study, women without an answer in the question regarding 
which prenatal test would they choose (main outcome), or women with no sufficient knowledge of Spanish 
or Catalan to be able to read and understand the questionnaire.  
 
Intervention and procedures 
For the experimental group, the intervention will consist of an extra 15-minute prenatal counseling before 
their first trimester scan. This intervention will require an explanation of all screening techniques for 
chromosomal abnormalities, including the first trimester combined test, cfDNA testing, invasive testing, and 
no screening at all. The intervention will be given by a single maternal-fetal medicine specialist who will explain 
all pros and cons of all given methods, giving also time to solve any question the woman may have. After the 
intervention (counseling), all participants will be asked to fill a questionnaire of twenty-one question regarding 
their knowledge, attitude and preferences about prenatal testing.  

For the control group, women will not be given an extra 15-minute counseling (no intervention), but 
will be directly asked to fill the questionnaire about their knowledge, attitude and preferences about prenatal 
testing.  
Sample size 
Sample size calculation has been made using an independent two-sample proportions likelihood-ratio test. 
We expect a 10% of women willing to have an invasive procedure as a first line test for aneuploidies in the 
control group, and a 25% difference to those in the experimental group that are given an extra 15-minute 
prenatal counseling, this yields a sample of 42 women per arm with a total of 84 subjects using a Type I error 
of 0.0501 and a power of 80% by a two-sided test.  
Randomization and intervention 
Participants will be randomized using an interactive Web-response system assigning patients in a 1:1 ratio to 
receive the extra counseling before first trimester assessment (intervention group) or nothing (control group). 
The allocation will be performed by the study manager. The maternal-fetal medicine specialist will be in charge 
of the participant’s enrolment and will also perform the intervention to the corresponding randomized group. 
This is an open-label study which means that the specialist and women will be aware of the allocation and 
intervention every time. 
Follow-up after the intervention 
After both groups (the experimental and control) have filled the questionnaire, the routine prenatal care will 
be given according to our hospital’s guidelines, which consists of a first trimester ultrasound scan, and the 
subsequent risk calculation for trisomy 21 and 18 with the use of the first trimester combined test. In case of 
risk greater than 1/250, an invasive diagnostic test will be offered. For risks between 1/250 and 1/1,000 a 
complementary first trimester genetic sonogram using secondary markers (nasal bone, tricuspid 
regurgitation, and ductus venosus) will be offered to re-calculate the risk for Down’s syndrome. For women 
with Down’s risk greater than 1/1000, no further evaluations will be offered.  
Questionnaire 
The questionnaire consists of twenty-one questions assessing the knowledge, preferences and attitude 
towards prenatal testing in the first trimester of pregnancy. The questionnaire will be divided in two parts. 

The first fourteen questions consist of demographic characteristics and obstetrics history, such as age, 
ethnicity, study level, marital status, religion, salary, employment, parity, previous miscarriages, previous 
terminations of pregnancy, previous congenital defects, pregnancy search time in months, type of conception, 
and who had provided any type of previous information about prenatal screening/testing. Women will be 
asked to select only one option for each question. All questions will have the possibility to answer as “Prefer 
not to answer”. The second part of que questionnaire will assess the preferences and attitudes towards 
prenatal testing; women will be asked to choose only one option for each question. The following questions 
will be included in the second part of the questionnaire: What influences you the most about prenatal testing? 
Who influenced you the most about prenatal testing? Would you like to choose your prenatal test? Which 
prenatal test would you choose? What is your opinion about termination? All questions include an “I don’t 
know answer”. The two final questions will ask the following, “What information regarding the results of 
prenatal testing is more important for you?” and “What is most important for you about prenatal testing?”. 
Women will be asked to score the first question from 1 to 5, meaning 1 the least important and 5 the most 
important, and from 1 to 6 in the same manner for the second question. These two questions will be assessed 
as means, where the question with the highest mean represents what is most important for the patient. 
Outcomes 
The primary outcome of the study is the desire to choose an invasive diagnostic testing as the first option of 
screening for chromosomal abnormalities. This will be measured in the questionnaire by asking the question: 
which prenatal test would you choose if given the opportunity? Women will be asked to choose only one 
answer between first trimester combined test, cell-free DNA, invasive testing. 
Statistical analysis 
Analysis will be conducted by intention-to-treat. Missing data for the main outcome will be handled by 
complete-data analysis because women without an answer on the main outcome will be excluded. All analyses 
will be divided by groups (control vs experimental group). Continuous data will be assessed for normality using 
the Kolmogorov-Smirnoff test. Normally distributed variables will be compared using t-test and expressed as 
mean and standard deviation (SD), while not normally distributed variables will be analyzed using the Mann-
Whitney-U test and expressed as medians and interquartile range (IQR). Quantitative variables will be 

compared using X2 test and expressed as numbers (n) and proportions (%). For the main outcome, preferences 
for prenatal testing among groups will be analyzed using absolute risk increase defined as the incidence of the 
outcome in the experimental group minus the incidence in the control group. The absolute risk increase will 
be depicted in a forest plot. A multivariate logistic regression will be performed to determine the Odds for 
choosing an invasive testing adjusting by demographic characteristics and previous counseling. Data will be 
analyzed using STATA v.15.3 for Mac (Texas College Station) and GraphPad Prism version 8.1.2 for Mac, 
GraphPad Software, San Diego, California USA, www.graphpad.com.