Influence of Prenatal Counseling in Invasive Testing
Influence of Prenatal Counseling in Invasive Testing
It is well established that screening for Down syndrome should be offered in the first
 trimester to each pregnant woman. The most common screening method is nowadays the first
 trimester combined test which consists of a Bayesian analysis of the a priori risk of
 maternal age for Down's syndrome, and the posterior risk combining serum biomarkers such as
 beta fraction of the human chorionic gonadotropin (β-hCG), pregnancy-associated plasma
 protein-A (PAPP-A), and nuchal translucency measurement. Women at high risk for trisomy 21 or
 18 using this combined test are eligible for chorionic villous sampling or amniocentesis for
 a final diagnosis. In recent years there has been a huge advance in prenatal screening for
 Down's syndrome with the advent of cell free DNA testing with higher sensitivity and
 specificity than the combined test, in which a positive result must be also confirmed by an
 invasive diagnostic procedure. But as the range of options broadens, also the need for health
 education to allow women to have an adequately informed decision process on which prenatal
 test better suits their needs. In multicultural cities, this has become especially important
 to integrate patient's values and expectations to an evidence-based decision regarding
 prenatal testing. There is high-quality evidence demonstrating that aversion to risk of fetal
 loss related to an invasive test may come from incomplete information, shaping the attitude
 towards which test to choose from the mother's point of view. And the disbelief that by
 taking cfDNA testing the risk of miscarriage would be reduced.

 Many information is available about preferences and attitudes in prenatal testing from
 Northern European studies, but scarce information is available from Southern Europe, where
 the amniocentesis rate in the nineties was as high as 40% of the urban pregnant population.

 The investigators hypothesize that when enough information is given before the initial
 screening, women will overcome aversion to invasive testing and will be more likely to choose
 this method as their first choice when compared to women having routine care.
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 invasive testing as the first-line
 option for the 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.

 Sample size calculation has been made using an independent two-sample proportions
 likelihood-ratio test. The investigators 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 is 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

 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 into 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
 the 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 the participants the most
 about prenatal testing? Who influenced the participants the most about prenatal testing?
 Would the participants like to choose their prenatal test? Which prenatal test would the
 participants choose? What is the participants' 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 the
 participants?" and "What is most important for the participants 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.

 The 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 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.
Inclusion Criteria:

 -  any pregnant woman attending the first trimester combined screening test for
 chromosomal abnormalities

 -  Singleton or twin pregnancies

 -  Between 11+0 and 13+6 weeks' gestation

 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)

 -  women with no sufficient knowledge of Spanish or Catalan to be able to read and
 understand the questionnaire