Early Anatomy Scan for Evaluation of Obese Pregnant Women (EASE-O): A Randomized Controlled Trial
Phase: NA
Conditions: Obesity
Sponsor: The University of Texas Health Science Center, Houston

IRB NUMBER: HSC-MS-20-0895 
  
IRB APPROVAL DATE: 08/12/2021 
EASE-O Protocol 1.1 8/10/20 
Page 1 of 41 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Title: Early Anatomy Scan for Evaluation of Obese Pregnant Women (EASE-O): A 
Randomized Controlled Trial 
 
NCT04639973 
 
Version Date: 08/12/2021 
 
 
 

IRB NUMBER: HSC-MS-20-0895 
  
IRB APPROVAL DATE: 08/12/2021 
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Early Anatomy Scan for Evaluation of Obese Pregnant Women (EASE-O): 
A Randomized Controlled Trial 
 
Study Protocol 
 
 
PROTOCOL NUMBER: 
Unassigned 
 
PROTOCOL TITLE: 
Early Anatomy Scan for Evaluation of Obese Pregnant Women (EASE-O): A 
Randomized Controlled Trial Study Protocol 
VERSION: 
1.3 
DATE: 
03/23/2021 
 
CORRESPONDING PRINCIPAL INVESTIGATOR: 
Cara Buskmiller, MD 
Maternal-Fetal Medicine Fellow, Obstetrics, Gynecology, and Reproductive Sciences 
Department, UTHealth 
 
COLLABORATORS: 
Edgar Hernandez-Andrade, MD PhD, Professor, Obstetrics, Gynecology, and 
Reproductive Sciences Department, UTHealth 
 
Baha Sibai, MD, Professor, Obstetrics, Gynecology, and Reproductive Sciences 
Department, UTHealth 
 
Farah Amro, MD, Fellow, Obstetrics, Gynecology, and Reproductive Sciences 
Department, UTHealth 
 
Matt Bicocca, MD, Fellow, Obstetrics, Gynecology, and Reproductive Sciences 
Department, UTHealth 
 
Corey Clifford, DO MBA, Fellow, Obstetrics, Gynecology, and Reproductive Sciences 
Department, UTHealth 
 
Conisha Holloman, MD, Fellow, Obstetrics, Gynecology, and Reproductive Sciences 
Department, UTHealth 
 
Michal Fishel Bartal, MD, Fellow, Obstetrics, Gynecology, and Reproductive Sciences 
Department, UTHealth 
 
Emma Qureshey, MD, Fellow, Obstetrics, Gynecology, and Reproductive Sciences 
Department, UTHealth 
 
Angela Stephens, MD, Fellow, Obstetrics, Gynecology, and Reproductive Sciences 
Department, UTHealth 
 
Beth Pineles, MD, PhD, Fellow, Obstetrics, Gynecology, and Reproductive Sciences 
Department, UTHealth 

IRB NUMBER: HSC-MS-20-0895 
  
IRB APPROVAL DATE: 08/12/2021 
EASE-O Protocol 1.1 8/10/20 
Page 3 of 41 
 
Sami Backley, MD, Fellow, Obstetrics, Gynecology, and Reproductive Sciences 
Department, UTHealth 
 
Felicia Ortiz, Maternal-Fetal Medicine Units network and Obstetrics, Gynecology, and 
Reproductive Sciences Department, UTHealth 
 
 
Name and address of the person authorized to sign the protocol and amendments: 
Cara Buskmiller, MD 
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
 
Name, title, address and telephone number(s) of the medical expert for the trial 
Edgar Hernandez-Andrade, MD, PhD 
Professor, Maternal Fetal Medicine 
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| 
 
Name and title of the investigator(s) and sub-investigators responsible for the trial 
with address and phone number(s) 
Cara Buskmiller, MD 
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||| 
 
Name and addresses of the clinical laboratories and/or other institutions involved in 
the trial 
Harris Health: LBJ Hospital 
|||||||||||||||||||||||||||||||||||||||||||||||||||||||| 
 
Memorial Hermann: TMC 
|||||||||||||||||||||||||||||||||||||||||||||||||| 
 
Memorial Hermann: Memorial City 
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||| 

IRB NUMBER: HSC-MS-20-0895 
  
IRB APPROVAL DATE: 08/12/2021 
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TABLE OF CONTENTS 
1. 
BACKGROUND AND RATIONALE ........................................................................................ 5 
1.1. 
GENERAL INTRODUCTION........................................................................................................................ 5 
1.2. 
RATIONALE AND JUSTIFICATION FOR THE STUDY ............................................................................... 5 
A. 
RATIONALE FOR THE STUDY PURPOSE ..................................................................................................... 5 
B. 
RATIONALE FOR STUDY POPULATION ........................................................................................................ 6 
C. 
RATIONALE FOR STUDY DESIGN ................................................................................................................. 6 
D. 
RATIONALE FOR DATING RANGES AND IMAGES REQUIRED ................................................................... 7 
2. 
HYPOTHESIS AND OBJECTIVES ......................................................................................... 9 
2.1. 
HYPOTHESIS .............................................................................................................................................. 9 
2.4. 
DEFINITIONS .............................................................................................................................................. 9 
2.5. 
POTENTIAL RISKS AND BENEFITS ........................................................................................................ 10 
A. 
END POINTS - EFFICACY ............................................................................................................................ 10 
B. 
END POINTS – SAFETY ............................................................................................................................... 10 
3.1. 
LIST THE NUMBER OF SUBJECTS TO BE ENROLLED .......................................................................... 11 
3.2. 
CRITERIA FOR RECRUITMENT ............................................................................................................... 11 
3.3. 
INCLUSION CRITERIA .............................................................................................................................. 11 
3.4. 
EXCLUSION CRITERIA ............................................................................................................................ 11 
3.5. 
WITHDRAWAL CRITERIA ........................................................................................................................ 11 
3.6. 
SUBJECT REPLACEMENT ....................................................................................................................... 11 
4. 
TRIAL SCHEDULE ................................................................................................................ 12 
4.1. 
RANDOMIZATION AND BLINDING .......................................................................................................... 12 
4.2. 
STUDY FLOW DIAGRAM ......................................................................................................................... 12 
4.3. 
STUDY VISITS AND PROCEDURES ....................................................................................................... 14 
5. 
TRIAL MATERIALS .............................................................................................................. 15 
5.1. 
ULTRASOUND MACHINES ...................................................................................................................... 15 
6. 
IMAGING DETAILS ............................................................................................................... 16 
6.1. 
RATIONALE FOR SELECTION OF REQUIRED IMAGES IN FIRST TRIMESTER ANATOMY ............... 16 
6.2. 
RATIONALE FOR SELECTION OF REQUIRED IMAGES IN SECOND TRIMESTER ANATOMY .......... 16 
6.3. 
SPECIFIC RESTRICTIONS / REQUIREMENTS ...................................................................................... 16 
6.4. 
BLINDING .................................................................................................................................................. 16 
6.5. 
CONCOMITANT THERAPY ....................................................................................................................... 16 
7. 
SAFETY MEASUREMENTS ................................................................................................. 16 
7.1. 
COLLECTING, RECORDING AND REPORTING OF ADVERSE EVENTS ............................................. 16 
7.2. 
SAFETY MONITORING PLAN .................................................................................................................. 17 
8. 
DATA ANALYSIS .................................................................................................................. 17 
8.1. 
DATA QUALITY ASSURANCE ................................................................................................................. 17 
8.2. 
DATA ENTRY AND STORAGE................................................................................................................. 17 
9. 
SAMPLE SIZE AND STATISTICAL METHODS ................................................................... 18 
9.1. 
DETERMINATION OF SAMPLE SIZE ...................................................................................................... 18 
9.2. 
STATISTICAL AND ANALYTICAL PLANS ................................................................................................ 18 
10. 
ETHICAL CONSIDERATIONS ......................................................................................... 18 
10.1. 
INFORMED CONSENT ............................................................................................................................. 18 
10.2. 
IRB REVIEW ............................................................................................................................................. 19 
10.3. 
CONFIDENTIALITY OF DATA AND PATIENT RECORDS....................................................................... 19 
11. 
PUBLICATIONS ................................................................................................................ 19 

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12. 
RETENTION OF TRIAL DOCUMENTS ............................................................................ 19 
13. 
REFERENCES .................................................................................................................. 19 
APPENDIX 1 .................................................................................................................................. 22 
APPENDIX 2 .................................................................................................................................. 25 
APPENDIX 3 .................................................................................................................................. 30 
APPENDIX 4 .................................................................................................................................. 33 

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STUDY PROTOCOL 
 
1. 
BACKGROUND AND RATIONALE 
 
1.1. 
General Introduction 
 
It is common practice in the United States and other countries worldwide to perform a 
detailed ultrasound to assess fetal anatomy, usually in the second trimester (18 
weeks to 22 weeks gestational age). This time period makes ultrasound scans 
feasible to perform and interpret, because the fetus is large enough, and organ 
systems are well developed. Increasingly sophisticated ultrasound technology has 
prompted earlier scans, and first trimester anatomy ultrasound has become more 
feasible, even for complex organs such as the fetal heart. In some prospective cohort 
studies, first trimester ultrasound offers equivalent imaging to second trimester 
ultrasound in obese patients, who are difficult to scan abdominally in the second 
trimester due to the layer of adipose tissue between the ultrasound transducer and 
the fetus. 
 
Obese women have lower rates of successful second trimester anatomy ultrasounds 
than do lean women. Difficult second trimester anatomy scans lead to suboptimal 
views and repeated scans, which has financial, emotional, and logistical costs. Fetal 
anatomy in these patients can be evaluated in the first trimester of pregnancy by 
ultrasound either transabdominally through the smaller layer of adipose at the pubic 
symphysis, or transvaginally, First trimester ultrasound has been studied in 
prospective cohort trials, it is safe and provides clear anatomic views, but randomized 
studies are necessary to determine whether this technique can decrease the number 
of scans required to completely evaluate the fetal anatomy in obese patients, without 
missing major anomalies. 
 
This study aims to fill that gap by studying if first trimester anatomy ultrasound can 
significantly contribute in the fetal anatomic evaluation in obese patients, and to 
establish whether it is a complementary or an alternative technique to second 
trimester anatomy ultrasound for this population. 
 
1.2. 
Rationale and justification for the Study 
 
a. 
Rationale for the Study Purpose 
Obesity is a prevalent disease in the US, affecting 600 million people and more 
women than men (1). Obesity makes ultrasound diagnosis difficult and 
simultaneously increases the rate of fetal anomalies (2). As BMI increases, anatomy 
visualization decreases in level I and level II ultrasounds (3-4). Timing of ultrasounds 
around 20 weeks seems to optimize completion in the 16 to 24 week range, and so 
for many years, a 20-week ultrasound has been the dominant practice in the United 
States and the world. 
 
However, recent studies have investigated earlier ultrasound for these patients, given 
that it may offer better imaging and earlier diagnosis, especially of severe anomalies. 
Ultrasound before 14 weeks can detect major anomalies but misses others (8-9). 
This is related to technological limitations such as image resolution of soft tissues and 
small structures, but also to the development of complex organs, such as the heart. 
Solutions have begun to emerge as the field of fetal imaging advances in 

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understanding what imaging findings are significant for major conditions such as 
facial clefts and neural tube defects (10-11). 
 
First trimester ultrasound has been recognized as a safe diagnostic technique for the 
embryo (8, 12-13). The field is moving towards standardizing and adopting the 
technique as an adjunct to second trimester ultrasound (15-16), and some studies 
have been done to compare its efficacy to second trimester ultrasound, and have 
found it equivalent (16) even in structures as complex as the heart (17). 
 
Given that there is some literature to support first trimester evaluation of fetal 
anatomy, this study proposes to randomize women to first trimester or second 
trimester anatomy ultrasound. This study design will allow comparison of the first 
trimester technique to the gold standard (second trimester anatomy ultrasound). All 
women in the intervention arm who receive a first trimester ultrasound will also 
receive a backup second trimester scan (termed a “gold standard scan”) to ensure no 
missed diagnosis of anomalies. 
 
 
b. 
Rationale for Study Population 
 
A BMI(Kg/M2) of ≥35 was chosen as the primary inclusion criteria given that the rate 
of completion of second trimester anatomy ultrasound does not significantly differ 
between women of BMI < 35, whether lean, overweight, or obese (7). The study 
population include women of child-bearing age and fetuses, even though these 
populations have some vulnerabilities, because it is designed to study an aspect of 
pregnancy. 
 
c. 
Rationale for Study Design 
 
Several cohort studies of first trimester ultrasound already exist (16, 17), but no 
randomized data is available. For these techniques (first and second trimester 
ultrasound) to be adequately compared, a randomized design is necessary. Other 
designs, such as before-and-after and prospective cohorts were considered, but 
given that this is a relatively simple intervention to directly compare, and 
randomization offers significant objectivity, a randomized controlled trial is proposed. 

IRB NUMBER: HSC-MS-20-0895 
  
IRB APPROVAL DATE: 08/12/2021 
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d. 
Rationale for Dating Ranges and Images Required 
 
Required images in the first trimester anatomy ultrasound (the intervention) were 
selected based on peer-reviewed literature on the subject of early fetal anatomy 
assessment. A detailed list of images required in the intervention is appended. The 
following is a list of required planes and peer-reviewed literature to support their use 
as key in the evaluation of major and minor fetal anomalies. This list of planes is 
deemed sufficient by multiple experts in the field and the International Society for 
Ultrasound in Obstetrics and Gynecology, or ISUOG (14, 19). 
 
1. Midsagittal fetus 
 
2. Placental cord insertion 
 
3. Profile 
 
4. Lateral ventricles 
 
5. BPD (transthalamic view) 
 
6. Head circumference 
 
7. Posterior fossa (cerebellum) 
 
8. Orbits 
 
9. Face (including retronasal triangle) 
 
10. Heart rate 
 
11. Situs 
 
12. Four chamber heart 
 
13. 3 vessel view 
 
14. Bladder 
 
15. Kidneys 
 
16. Abdominal circumference 
 
17. Fetal cord insertion 
 
18. 3 vessel cord 
 
19. Extremities 
 
20. Spine 
 
The first trimester required images largely correspond with second trimester required 
images, with very few differences which reflect that some structures (e.g. the lip) are 
hard to see in the first trimester, and are replaced by a feasible alternative (e.g. the 
retronasal triangle) based on peer-reviewed literature. 

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All ultrasounds performed in the second trimester, both the GSS for the intervention 
arm and the anatomy evaluation in the comparison arm, will be evaluated for 
completion based on UT’s proprietary second trimester protocol, which abides by 
standards set out by the International Society of Ultrasound in Obstetrics & 
Gynecology (ISUOG) and the American Institute of Ultrasound in Medicine (AIUM) 
(20, 22-23). A list of images required for the comparison is given here in brief. 
1. Fetal position 
 
2. Placental cord insertion 
 
3. Profile 
 
4. Lateral ventricles 
 
5. BPD (transthalamic view) 
 
6. Head circumference 
 
7. Posterior fossa (cerebellum) 
 
8. Choroid plexus 
 
9. Orbits 
 
10. Face 
 
11. Nose-lips 
 
12. Heart rate 
 
13. Heart rate 
 
14. Situs 
 
15. Four chamber heart 
 
16. 3 vessel view 
 
17. Interventricular septum 
 
18. Bladder 
 
19. Kidneys 
 
20. Abdominal circumference 
 
21. Fetal cord insertion 
 
22. 3 vessel cord 
 
23. Diaphragm 

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24. Extremities (including femur length, humerus length, hands, feet) 
 
2. 
HYPOTHESIS AND OBJECTIVES 
 
2.1. 
Hypothesis 
 
1. An ultrasound evaluation in the late first trimester (12w0d to 13w6d) is more 
likely to provide a complete fetal anatomical evaluation than an ultrasound 
evaluation done in the second trimester (18w0d to 22w6d) of pregnancy in 
obese women. 
 
2. Ultrasound evaluation of fetal anatomy in the first trimester (12w0d to 
13w6d) combined with conventional ultrasound evaluation of fetal anatomy 
in the second trimester (18w0d to 22w6d) will provide with more information 
than either in isolation. 
 
 
2.2. 
Primary Objectives 
 
Assess the feasibility of ultrasound in the first trimester at our Center with our 
equipment and personnel. Assess the completion rate of ultrasounds for fetal 
anatomy in the first trimester (12w0d to 13w6d) compared to completion rates of 
ultrasounds for fetal anatomy in the second trimester (18w0d to 22w6d) in obese 
women. 
 
2.3. 
Secondary Objectives 
 
Assess the completion rate of the combination of one ultrasound in the first trimester 
and one in the second trimesters (12w0d to 13w6d and 18w0d to 22w6d), compared 
to the individual completion rates of both evaluations in obese women. 
 
 
2.4. 
Primary Outcome 
 
The primary outcome is the completion rate (number of scans that see all the views 
listed on pages 7 or 8 divided by total number of scans in that group) for first trimester 
ultrasounds, compared to the same metrics obtained in second trimester ultrasounds. 
 
2.5. 
Secondary Outcome 
 
Secondary outcomes include: 
1. Completion rate of both first and second trimester scans (when considered as a 
single instrument to visualize the fetal anatomy, what is the rate of complete 
visualization divided by all women?) 
2. Total length of scanning time in the first trimester ultrasound group 
3. Number of anomalies identified (and missed) in each group 
4. Neonatal outcomes (survival, gestational age at delivery, NICU admission, 
hospital LOS, neonatal morbidities including respiratory distress syndrome, 
transient tachypnea of the newborn, intraventricular haemorrhage, necrotizing 
enterocolitis) 
5. Patient feedback to standardized surveys (see attached) 

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6. Cost of intervention compared to usual care (cost benefit analysis based on 
whether more ultrasounds were done in cases of early discovery of anomalies) 
 
 
a. 
End Points - Efficacy 
Anticipated benefits of first trimester detailed anatomy scan include a higher 
completion rate the initial ultrasound performed for anatomy. We anticipate that this 
will decrease the number of times future obstetric patients will have to return for 
additional ultrasounds. There will be no direct benefits to the participants in the prior 
trial apart from the intervention arm gaining an additional look at their baby, which 
may have potential social or psychological benefits. 
 
b. 
End Points – Safety 
Anticipated risks of ultrasound are low. While there is theoretical risk of the effects of 
high-output ultrasound techniques, such as color Doppler, causing increased core 
body temperature and possible teratogenic effects in the first trimester, there is not a 
well-accepted incidence of ultrasound-related fetal adverse outcomes, and ultrasound 
is generally deemed of low or no risk by professional organizations (21). Available 
guidelines suggest that judicious clinical use of ultrasound as appropriate to the 
patient risk profile should be employed (19-23). 
 
Of note, expert opinion on this matter deems all patients included in this study as high 
risk for anatomic abnormalities (14), which justifies detailed investigation, including 
Doppler ultrasound. 
 
3. 
STUDY POPULATION 
 
Broadly speaking, the population is obese pregnant women with BMI ≥35 (Kg/M2). 
 
3.1. 
List the number of subjects to be enrolled. 
A sample size of 118 women was calculated based on the primary outcome of initial 
scans which completely clear the fetal anatomy (see below for details of sample size 
calculation). It is necessary to include women in this study as this proposes a 
technique only possible in pregnancy. Minorities will be included to strengthen 
external validity of the study. Children will not be recruited. 
 
3.2. 
Criteria for Recruitment 
 
Once a potential subject expresses interest in participation, she will be asked to 
undergo a brief ultrasound to verify her gestational age. This ultrasound will be free of 
charge, will take approximately 5 minutes, and will not be entered in her medical 
record or saved as study images. This is to confirm viability gestational age, and 
number of fetuses.) 
 
3.3. 
Inclusion Criteria 
 
The subject must meet all of the following inclusion criteria to participate in this study: 
− 
BMI ≥ 35 
− 
Age 18-50 years 

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− 
Presented for ultrasound before 14 weeks at UT Professional Building, 
Memorial City, Bellaire, or Lyndon-Baines Johnson clinics 
− 
Primary language is English or Spanish 
− 
Consent to an extra transvaginal ultrasound if needed 
− 
Singleton gestation 
− 
No previous anomalies known before consent 
− 
Missed abortion (nonviable pregnancy) 
 
Missed abortion will be defined by ultrasound findings during recruitment according to 
Doubilet et al 2013 (18), which is the widely-accepted standard in the United States. 
 
3.4. 
Exclusion Criteria 
 
All subjects meeting any of the following criteria at baseline will be excluded from 
analysis, although will be reported as part of study flow: 
− 
Elective abortion after recruitment 
− 
Missed abortion after first trimester ultrasound 
− 
Did not receive second trimester ultrasound 
 
Missed abortion will be defined by ultrasound findings during recruitment according to 
Doubilet et al 2013 (18), which is the widely-accepted standard in the United States. 
 
3.5. 
Withdrawal Criteria 
 
An interim analysis is planned at recruitment of 50% of the patients (n=59) and if first 
trimester ultrasound is not completable in at least 50% of patients, the study will be 
stopped. An individual patient may withdraw from the study at any time. 
 
3.6. 
Subject Replacement 
Subjects who withdraw from the study will be replaced. 
 
 
4. 
TRIAL SCHEDULE 
 
September 2020 - June 2021 
Recruitment 
December 2020 
Goal: 25% recruitment at end of month 
February 2021 
Goal: 50% recruitment at end of month 
May 2021 
Goal: 75% of recruitment mid-month 
July 2021-August 2021 
Follow up on delivery records, clean data 
August 2021 
Data analysis, review by entire team 
September - November 2021 
Manuscript preparation 
December 2021 
Manuscript submission 

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4.1. 
Randomization and Blinding 
 
Randomization will be carried out in a 1:1 ratio with block size 4, stratified into three 
groups by pre-pregnancy BMI (see below) using RedCap. 
 
Group 1 (First trimester ultrasound) 
- 
BMI 35-39.9: 19 patients 
- 
BMI 40-44.9: 20 patients 
- 
BMI >45: 20 patients 
 
Group 2 (Second trimester anatomy ultrasound) 
- 
BMI 35-39.9: 19 patients 
- 
BMI 40-44.9: 20 patients 
- 
BMI >45: 20 patients 
 
There is no plan for breaking of randomization codes, as randomization will be done 
through RedCap, nor are there plans for unmasking. 
 
4.2. 
Study Flow Diagram 

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4.3. 
Study Visits and Procedures 
 
a. Screening Visits and Procedures 
 
Research staff will screen the schedules of the ultrasound clinics at Memorial City, 
Bellaire, UT Professional Building, LBJ, and Harris Health Aldine ultrasound clinics 
for patients undergoing clinically indicated ultrasounds before 14 weeks gestational 
age. (These existing clinic visits are usually for dating ultrasound or nuchal 
translucency, an early assessment of a marker of aneuploidy.) Research staff will 
approach patients at these visits and describe the study. If the patient is interested in 
participation, the sequence of events that should occur include confirmation of 
eligibility with a 5-minute ultrasound to determine a single viable fetus before 14 
weeks. This is the only procedure necessary before recruitment. If the patient is 
eligible according to this screening ultrasound, she can be randomized at that time. 
 
b. Study Visits and Procedures 
 
After the screening ultrasound confirms eligibility and a patient is given informed 
consent, the patient can then be randomized. If the patient is randomized to the 
intervention (detailed first trimester anatomy ultrasound), this scan is performed at the 
randomization visit if the patient is between 12w0d and 13w6d. If she is less than 
12w0d, a separate study visit is scheduled for a date at her convenience during the 
days she is between 12w0d and 13w6d. A dedicated room and time slots have been 
made available for these study visits at Memorial Hermann Southwest and at the 
Fetal Center at UTPB. This separate scan/visit is not billed as it is not part of the 
standard of care. 
 
After this detailed research ultrasound, which will be limited to 15 minutes, she then 
receives her clinically indicated dating ultrasound or nuchal translucency 
measurement. The total estimated time of all these ultrasounds is expected to be 
approximately 30 minutes, with breaks in between to allow the patient some 
movement and the opportunity to use the rest room, and to allow the exchange of 
operators (research staff vs clinical staff) and the creation of distinct records 
(research ultrasound is not saved to electronic medical records, so a new scanning 
encounter must be opened for the clinical ultrasound that day). The patient will 
complete a survey about her satisfaction with this technique via email. In addition, as 
a safety measure, if an anomaly is suspected on the day of the detailed first trimester 
anatomy scan, the patient will be unblinded. The research team will inform the clinical 
team so that a more detailed evaluation can be done and so that this information can 
enter the clinical record and affect clinical management. 
 
Patients randomized to the intervention arm are later scheduled for a second 
trimester ultrasound by the clinical team, as this is part of standard obstetrical care. 
Research staff will ensure patients have this scan scheduled and completed, as it is 
part of study procedure. Data about this scan will be recorded in the patient’s 
research record. This scan can be repeated as indicated according to UT’s protocol 
for assessing anatomy. 
 
If the patient is randomized to the comparison arm, she does not undergo a detailed 
first trimester ultrasound that day, but she does receive her clinically indicated limited 
ultrasound for dating or for nuchal translucency. She then undergoes a second 

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trimester ultrasound by the clinical team as part of standard obstetrical care and 
completes a survey regarding her satisfaction with this technique via email. Research 
staff will ensure patients have this scan scheduled and completed, as it is part of 
study procedure. Data about this scan will be recorded in the patient’s research 
record. This scan can be repeated as indicated according to UT’s protocol for 
assessing anatomy. 
 
c. Final Study Visit: 
 
The final study visit is denoted by completion of the second trimester gold standard 
scan (GSS) for patients randomized to the intervention arm, and at the completion of 
the second trimester anatomy ultrasound for patients randomized to the comparison 
arm. Participants will continue to be followed through their pregnancy to document 
the number of ultrasounds required to complete the fetal anatomy evaluation. 
 
d. Post Study Follow up and Procedures 
 
Medical records will be reviewed after each study participant’s due date to assess 
whether delivery has occurred and to record delivery outcomes from the medical 
records, when available. This is chiefly so that a post-natal evaluation can be 
recorded to confirm or exclude anatomical anomalies. Delivery outcomes are not a 
primary outcome and request of outside delivery records will not be required for a 
subject’s record to be marked as completely collected. 
 
Adverse outcomes, including discomfort during ultrasound as well as neonatal 
outcomes, will be recorded in the subject’s research record. 
 
e. Discontinuation Visit and Procedures 
 
Subjects may withdraw voluntarily from participation in the study at any time. 
Subjects may also withdraw voluntarily from receiving the study intervention for any 
reason. 
 
If a patient in the intervention arm withdraws from the study during to her first 
trimester anatomy ultrasound, she will be asked to complete the survey regarding her 
experience regardless of the duration of the first trimester ultrasound. She will then 
undergo her clinically indicated ultrasound (which are not transvaginal). 
 
If a subject in the intervention arm withdraws from the study prior to her second 
trimester GSS ultrasound (done as “back up” for the intervention), a standard email 
will be sent to her confirming her withdrawal and encouraging her to seek a second 
trimester (standard of care) anatomy ultrasound as the anatomy evaluation she had 
in the first trimester is considered experimental. 
 
If a subject in the comparison arm withdraws from the study prior to her second 
trimester anatomy ultrasound, she will not be required to complete the survey about 
her experience. A standard email will be sent to her confirming her withdrawal and 
encouraging her to seek a second trimester (standard of care) anatomy ultrasound 
outside the study. 
 
If voluntary withdrawal occurs, the subject will be given standard care under medical 
supervision until the symptoms of any adverse event resolve or the subject’s 
condition becomes stable. 

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5. 
TRIAL MATERIALS 
 
5.1. 
Ultrasound Systems 
 
All scans (screening ultrasound, first-trimester anatomy scan, GSS, and second 
trimester anatomy scans) will be performed using General Electric (GE) E8 or E10 
machines, which are FDA approved for ultrasound in the first and second trimester 
(E8 510(k) number: K170445, E10 510(k) number: K173555). Approval for the E8 is 
available at https://www.accessdata.fda.gov/cdrh_docs/pdf17/K170445.pdf (last 
accessed 7/30/20) and approval for the E10 is available at 
https://www.accessdata.fda.gov/cdrh_docs/pdf17/K173555.pdf (last accessed 
7/30/20). 
 
6. 
BLINDING 
Patients are not blinded to their group as they are aware of the timing of their detailed 
ultrasound. The clinical team will not be informed of the patient’s randomization 
assignment, images from research ultrasounds will not be available to the clinical 
team, and the clinical team will not be made aware of whether the second trimester 
scan done by them is for comparison to the gold standard (the GSS in intervention 
arm patients) or for anatomy (in comparison arm patients). 
 
Patients and the care team will be unblended from the results of the first trimester 
exam if there is an anomaly. There are no other plans for unblinding. 
 
7. 
SAFETY MEASUREMENTS 
7.1. 
Collecting, Recording and Reporting of Adverse Events 
 
Adverse events are not likely during a study of ultrasound, given the very low risk of 
fetal effects during anatomy ultrasound (19-23). Fetuses of mothers in the 
intervention arm will be evaluated by the gold standard (GSS) in the second 
trimester, in order to rule out any missed anomalies. Fetuses in both arms are 
exposed to similar amounts of ultrasound time (all fetuses have at least two 
ultrasounds in the first trimester and one in the second trimester). 
 
Intervention arm total number of scans: 
1. Screening ultrasound (estimated time 2 minutes) 
2. First trimester anatomy ultrasound (estimated time 25 minutes) 
3. Scheduled limited first trimester ultrasound (estimated time 10 minutes) 
4. GSS in second trimester to ensure standard of care is met (estimated time 45 
minutes) 
 
Comparison arm total number of scans: 
1. Screening ultrasound (estimated time 2 minutes) 
2. Scheduled limited first trimester ultrasound (estimated time 10 minutes) 
3. Second trimester anatomy ultrasound (estimated time 30 minutes) 
Multiple ultrasounds are common in this population. 

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Maternal adverse effects including discomfort will be noted in the study database but 
will not be reported to a study safety monitor. 
 
7.2. 
Safety Monitoring Plan 
 
The research ultrasound will be stored locally on an E8 machine or on a hard drive 
owned and protected by UT. It will not be available in the medical record. Data 
regarding ultrasound (length in minutes, date, gestational age, findings) will be stored 
in RedCap. Maternal and neonatal outcomes will be collected from Care4 or Epic 
(depending on the location of delivery) and stored in RedCap. 
 
Adverse effects are not expected from an ultrasound intervention, although 
discomfort especially with transvaginal ultrasound is frequently reported by patients. 
In the case of patient discomfort with the ultrasound exam, the exam will be paused 
and the patient asked for permission to continue. If the patient declines the 
continuation of the exam, the exam will stop and completion will be assessed based 
on the images obtained before that point. 
 
8. 
DATA ANALYSIS 
8.1. 
Data Quality Assurance 
 
Data will be checked by at least two members of the research team for integrity. The 
entire study team (CB, EH, BS) will have access to study documents in RedCap and 
to ultrasound images on the protected UT drive (encrypted and kept in a locked office 
in the Medical School Building at the medical center campus). A linking log will be 
used to limit spread of PHI into the RedCap record, so that inadvertent download of 
data does not compromise patient confidentiality and anonymity. This linking log will 
be kept in the same system as the data but will not be accessible with the dataset or 
ultrasound images, in order to protect patient identifying variables as much as 
possible. 
 
8.2. 
Data Entry and Storage 
 
Data will be entered directly by patients into RedCap with research staff supervision 
(for demographics) or independently (for survey replies), or by the research staff. A 
linking log will be used. The linking log and images will be destroyed at the close of 
the study (upon publication). De-identified records will be retained for 5 years and 
made available upon academic request to the corresponding author. 
 
9. 
SAMPLE SIZE AND STATISTICAL METHODS 
 
9.1. 
Determination of Sample Size 
 
Approximately 85% of lean women only require a single anatomy ultrasound, as it 
completely images all parts of the fetal anatomy. A review of UT’s data on anatomy 
ultrasound in the obese was performed to obtain data on our completion rates in 
order to calculate sample size. In obese women, only 70% of initial scans are 
complete and women are required to return for repeated ultrasounds, occasionally 3 
or more times. Given that the primary hypothesis is that first trimester ultrasound will 
remove the difficulty associated with obesity, an increase from 70% completion to 
85% completion is anticipated. A sample size of 118 is required to detect a 15% 

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increase in the number of complete initial scans with 80% power and alpha of 0.05. A 
sample size was also calculated for a Bayesian analysis, which would require fewer 
than 118 women with the same suppositions. 
 
Bayesian sample size per group to obtain 80% power under different scenarios 
Usual Care 
Outcome Rate 
Usual Care 
Outcome Rate 
Usual Care 
Outcome Rate 
Usual Care 
Outcome Rate 
70% 
70% 
70% 
70% 
70% 
70% 
70% 
70% 
65% 
65% 
65% 
65% 
65% 
65% 
65% 
65% 
 
It is planned to recruit 118 women to lend the maximum power to the analysis. 
Bayesian analysis will be performed only if recruitment proves challenging. 
 
To obtain a sample size of 118 given a recruitment rate of 50%, 236 women will need 
to be approached over an expected recruitment time of 2 years. 
 
9.2. 
Statistical and Analytical Plans 
Analysis will be carried out according to the intention-to-treat principle. All 
randomized subjects will be included in analyses for which they have data. 
Frequentist statistics will be reported, including mean number of scans in each group 
(compared with t tests, with ANOVA between classes of obesity), the proportion of 
complete scans in each group (compared with chi square test), and the mean total 
scan time (t tests). Secondary outcomes will also be analysed with a frequentist 
approach. Descriptive statistics will also be provided about anomalies found and 
missed (anticipated to be low, so likely few significant findings to report). In addition, 
patient perspectives will be described. 
 
10. 
ETHICAL CONSIDERATIONS 
10.1. Informed Consent 
 
Informed consent will be obtained in either English or Spanish and will preferably be 
performed by e-consenting (no paper copy of the consent). Patients will consent via a 
tablet or mobile device directly into RedCap and will be provided with an emailed 
copy of their consent form. 
 
10.2. IRB review 
 
A copy of the protocol will be submitted to the Institutional Review Board (IRB) for 
written approval. The Principal Investigator will obtain approval from the IRB for all 
subsequent protocol amendments. 
 
10.3. Confidentiality of Data and Patient Records 
 
Subject confidentiality will be maintained and all records will be securely stored. 

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11. 
PUBLICATIONS 
 
We anticipate three primary publications coming out of this study. Completion rates 
and multiple second outcomes can be published in journals of maternal-fetal 
medicine or ultrasound. 
 
12. 
RETENTION OF TRIAL DOCUMENTS 
 
All records, including all source documentation (containing evidence to study 
eligibility, history and physical findings, laboratory data, etc) as well as IRB records 
and regulatory documents will be retained by the PI in a secure storage facility. The 
records will be accessible for inspection and copying by authorized authorities. 
 
 
13. 
REFERENCES 
 
1. Ogden CL, et al. Prevalence of childhood and adult obesity in the United States. 
JAMA 2014. 
 
2. Hendler I, et al. Suboptimal second trimester ultrasonographic visualization of the 
fetal heart in obese women: should we repeat the examination? J Ultrasound 
Med 2005. 
 
3. Tsai PJS, et al. Obesity and the challenges of ultrasound fetal abnormality 
diagnosis. Best Pract Res Clin Obstet Gynaecol 2015. 
 
4. Gabbay-Benziv, et al. Birth defects in pregestational diabetes: Defect range, 
glycemic threshold and pathogenesis. World J Diabetes 2015. 
 
5. Ylinen K, et al. Risk of minor and major fetal malformations in diabetics with high 
haemoglobin A1c values in early pregnancy.Br Med J (Clin Res Ed) 1984. 
 
6. Thornburg LL, et al. Fetal anatomic evaluation in the overweight and obese 
gravida. Ultrasound Obstet Gynecol 2009 
 
7. Pasko D, et al. Completion and Sensitivity of the Second-Trimester Fetal 
Anatomic Survey in Obese Gravidas. J Ultrasound Med 2016. 
 
8. Rossi and Prefumo. Accuracy of Ultrasonography at 11–14 Weeks of Gestation 
for Detection of Fetal Structural Anomalies. Obstet Gynecol 2013. 
 
9. Karim JN et al. Systematic Review of First-Trimester Ultrasound Screening for 
Detection of Fetal Structural Anomalies and Factors That Affect Screening 
Performance. Obstet Gynecol Surv 2018. 
 
10. Chaoui R et al. Maxillary gap at 11–13 weeks’ gestation: marker of cleft lip and 
palate. Ultrasound Obstet Gynecol 2015. 
 
11. Maruotti G et al. Diagnostic accuracy of intracranial translucency in detecting 
spina bifida: a systematic review and meta-analysis. Prenat Diagn 2016. 

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12. Castro et al, Physical Principles, Methodology, Consistency, and Safety in 
Doppler Assessment of the Fetal-Placental Circulation. Ginecol Obstet Mex 
2007. 
 
13. Salvesen KA, et al. ISUOG statement on the safe use of Doppler in the 11 to 13 
+ 6-week fetal ultrasound examination. Ultrasound Obstet Gynecol 2011. 
 
14. Abuhamad, Alfred and Rabih Chaoui. First Trimester Ultrasound Diagnosis of 
Fetal Abnormalities. Wolters Kluwer: USA. 2018. 
 
15. Hernandez-Andrade E, et al. Early evaluation of the fetal heart. Fetal Diagn Ther 
2017. 
 
16. Romary L et al. The Role of Early Gestation Ultrasound in the Assessment of 
Fetal Anatomy in Maternal Obesity. J Ultrasound Med 2017. 
 
17. Majeed A et al. Can Ultrasound in Early Gestation Improve Visualization of Fetal 
Cardiac Structures in Obese Pregnant Women? J Ultrasound Med 2019. 
 
18. Doubilet PM, Benson CB, Bourne T, et al. Diagnostic criteria for nonviable 
pregnancy early in the first trimester. N Engl J Med. 2013;369(15):1443-1451. 
doi:10.1056/NEJMra1302417 
 
19. Salomon LJ, Alfirevic Z, Bilardo CM, et al. ISUOG practice guidelines: 
performance of first-trimester fetal ultrasound scan [published correction appears 
in Ultrasound Obstet Gynecol. 2013 Feb;41(2):240]. Ultrasound Obstet Gynecol. 
2013;41(1):102-113. doi:10.1002/uog.12342 
 
20. Salomon LJ, Alfirevic Z, Berghella V, et al. Practice guidelines for performance of 
the routine mid-trimester fetal ultrasound scan. Ultrasound Obstet Gynecol. 
2011;37(1):116-126. doi:10.1002/uog.8831 
 
21. Jain C. ACOG Committee Opinion No. 723: Guidelines for Diagnostic Imaging 
During Pregnancy and Lactation. Obstet Gynecol. 2019;133(1):186. 
doi:10.1097/AOG.0000000000003049 
 
22. ACR–ACOG–AIUM Practice guideline for the performance of obstetrical 
ultrasound. Obstetrical Ultrasound. Rev 2007. Accessed from 
https://www.pedrad.org/Portals/5/Subspecialties/OB%20Ultrasound%20practice 
%20guidelines.pdf 8/10/20. 
 
23. AIUM-ACR-ACOG-SMFM-SRU Practice Parameter for the Performance of 
Standard Diagnostic Obstetric Ultrasound Examinations. J Ultrasound Med. 
2018;37(11):E13-E24. doi:10.1002/jum.14831 
 
 
List of Attachments 
 
Appendix 1 
Questionnaires used in the Trial 
Appendix 2 
Consent Form 

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Appendix 3 
Standardized Patient Emails 

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APPENDIX 1 
Patient survey after detailed anatomy ultrasound for EASE-O 
Version 1.0, last revised 8/2/20 
 
 
This survey is 12 questions long and should take about 15 minutes. 
Recently, you had a “[first/second] trimester detailed anatomy ultrasound,” or an 
ultrasound that looked at the body parts of your baby in detail at [12-14/18-22] weeks. 
These questions will ask you about your experience with your ultrasound and your 
opinions about finding birth defects early in pregnancy. 
1. Overall, how satisfied were you with today’s ultrasound? 
a. Very satisfied 
b. Somewhat satisfied 
c. Neither satisfied nor dissatisfied 
d. Somewhat dissatisfied 
e. Very dissatisfied 
 
2. How would you rate the level of discomfort required by this ultrasound? 
a. Very comfortable 
b. Somewhat comfortable 
c. Neither comfortable nor uncomfortable 
d. Somewhat uncomfortable 
e. Very uncomfortable 
 
3. How would you rate the length of time it took to complete this ultrasound? Don’t 
count the time it took to do other things, like park or wait in the waiting room. 
a. Much longer than I expected 
b. A little longer than I expected 
c. About the time I expected 
d. A little shorter than I expected 
e. Much shorter than I expected 
 
4. How satisfied are you with the length of time it took to complete this ultrasound? 
Don’t count the time it took to do other things, like park or wait in the waiting 
room. 
a. Very satisfied 
b. Somewhat satisfied 
c. Neither satisfied nor dissatisfied 
d. Somewhat dissatisfied 
e. Very dissatisfied 
 
5. How likely are you to recommend [first/second] trimester anatomy screening to 
other pregnant women? 
a. Very likely 
b. Somewhat unlikely 
c. Neither likely nor unlikely 
d. Somewhat unlikely 

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e. Very unlikely 
 
The next questions ask for your opinions on finding out about birth defects early. Most 
birth defects are discovered at 18-22 weeks, but EASE-O is studying ultrasounds which 
can discover many of the same birth defects at 12-14 weeks. For this section, remember 
that: 
- 
Finding out about a birth defect early can lead to more ultrasounds and testing 
- 
Finding out about a birth defect early means a longer time knowing about the 
problem, when there may be no therapy for the fetus until birth 
- 
Abortion (ending a pregnancy before birth) is safer for the woman when done 
earlier in pregnancy 
 
6. For you, how important is finding out about any birth defects early in your 
pregnancy? 
a. Very important 
b. Important 
c. Fairly important 
d. Slightly important 
e. Not important 
 
7. How much testing would you seek if an abnormal ultrasound finding was 
discovered during your detailed scan? 
a. All available testing, even invasive options 
b. Some available testing, only invasive options if highly recommended 
c. Some available testing, but not invasive options 
d. Very little testing, definitely no invasive options 
e. No testing at all, even if recommended 
 
8. If there was a therapy or surgery that you could undergo during pregnancy for a 
birth defect discovered in your fetus, how likely would you be to agree to it? 
a. Very likely 
b. Somewhat unlikely 
c. Neither likely nor unlikely 
d. Somewhat unlikely 
e. Very unlikely 
 
9. Some women in this study got an ultrasound at [18 to 22/12 to 14] weeks instead 
of when you got your ultrasound. Please tell us whether you agree or disagree 
with the following statement: “I wish I could have been in the other group, and 
gotten my detailed anatomy ultrasound at [18 to 22/12 to 14] weeks.” 
a. Strongly agree 
b. Agree 
c. Neither agree nor disagree 
d. Disagree 
e. Strongly disagree 

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10. You got your detailed anatomy ultrasound at at [12-14/18-22] weeks. If given the 
choice in another pregnancy (even if another baby is not your plan), how likely 
are you to choose the same timing again? 
a. Very likely 
b. Somewhat likely 
c. Neither likely nor unlikely 
d. Somewhat unlikely 
e. Very unlikely 
The last two questions involve questions about abortion. These questions may be 
sensitive and you may skip them. If you can answer them, you help us understand how 
women feel about issues that affect early diagnosis of birth defects. 
[SKIP ENTIRE SECTION] 
11. Some birth defects are very serious and limit the fetus’ length of life and/or future 
quality of life. In certain cases, abortion is offered as an option. What are your 
feelings on abortion (ending a pregnancy before birth) in general? 
a. Very supportive of abortion 
b. Somewhat supportive of abortion 
c. Neither supportive nor opposed to abortion 
d. Somewhat opposed to abortion 
e. Very opposed to abortion 
f. 
[SKIP THIS QUESTION] 
 
12. Imagine that you were pregnant with a fetus with a very serious birth defect, that 
limited the fetus’ length of life and/or future quality of life. If your doctor offered 
abortion as an option, how likely would you be to seek an abortion for yourself? 
a. Very likely 
b. Somewhat likely 
c. Neither likely nor unlikely 
d. Somewhat unlikely 
e. Very unlikely 
f. 
[SKIP THIS QUESTION] 
Thank you for your participation! This survey helps us understand how you feel about 
when you get your ultrasound and what you want to do with the information. 
Autopopulated fields: 
[Study ID] 
[Survey completion date] 
[EDD] 
[Gestational age at survey completion] 
[Group: intervention/comparison] 
[Primary outcome (initial anatomy scan complete?): Y/N] 

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APPENDIX 2 
CONSENT TO TAKE PART IN RESEARCH 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX 3 
Standardized Emails for EASE-O 
Version 1.0, last revised 8/2/20 
 
Standardized Welcome Email 
Dear [Name], 
 
Thank you for participating in EASE-O, a randomized clinical trial to find out when is the 
best time for a detailed anatomy ultrasound in women with a BMI of 35 or greater. We’re 
so glad you’re part of the study. If you haven’t already filled out your demographics with 
the research staff, please click this link to do so. 
 
You are in the group that gets a detailed anatomy ultrasound in the [first/second] 
trimester. Based on this, a survey [has been/will be] made available to you about your 
experience after your detailed anatomy ultrasound. Filling out this survey helps us 
understand what women like you prefer regarding their ultrasounds. We want to hear 
from you! 
 
Because you are in the group that gets a detailed anatomy ultrasound in the 
[first/second] trimester, your next step in the study is to get [an ultrasound to check on 
the baby/your detailed anatomy ultrasound] between 18 and 22 weeks, which will be 
scheduled by your doctor. You don’t have to do anything—we’ll take care of everything, 
and all your information will be kept confidential. 
 
If you have any concerns about the study or want to withdraw, please email 
cara.m.buskmiller@uth.tmc.edu. Have a great day! 
 
Sincerely, 
 
Cara Buskmiller, MD 
Principle Investigator, EASE-O 
 
Standardized second trimester detailed anatomy survey email (comparison arm 
after detailed second trimester anatomy scan) 
Dear [Name], 
 
I hope you haven’t forgotten about EASE-O, a randomized clinical trial to find out when 
is the best time for a detailed anatomy ultrasound in women with a BMI of 35 or greater. 
You’re almost done with your participation! [If you haven’t already filled out your 
demographics with the research staff, please click this link to do so.] 
 
You are in the group that gets a detailed anatomy ultrasound in the second trimester. 
Based on this, you may have already had your detailed anatomy ultrasound, or it might 
be coming up soon! After your ultrasound, please fill out this survey. Filling out this 
survey helps us understand what women like you prefer regarding their ultrasounds. We 
want to hear from you! 
 
This is the last step for you in the study. After this survey, you don’t have to do 
anything—we’ll take care of everything, and all your information will be kept confidential. 
 
If you have any concerns about the study or want to withdraw, please email 
cara.m.buskmiller@uth.tmc.edu. Have a great day! 

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Sincerely, 
 
Cara Buskmiller, MD 
Principle Investigator, EASE-O 
 
Standardized second trimester safety ultrasound reminder (intervention arm) 
Dear [Name], 
 
I hope you haven’t forgotten about EASE-O, a randomized clinical trial to find out when 
is the best time for a detailed anatomy ultrasound in women with a BMI of 35 or greater. 
You’re almost done with your participation! [If you haven’t already filled out your 
demographics with the research staff, please click this link to do so.] 
 
You are in the group that got a detailed anatomy ultrasound in the first trimester. Even 
though that was neat, that ultrasounds is still considered experimental (that’s why we are 
researching them)! You deserve to have a complete re-evaluation of your baby’s body 
parts between 18-22 weeks, which is coming up soon. 
 
This safety measure is the last step for you in the study. Afterwards, you don’t have to 
do anything—we’ll take care of everything, and all your information will be kept 
confidential. If you have any concerns about the study or want to withdraw, please email 
cara.m.buskmiller@uth.tmc.edu. Have a great day! 
 
Sincerely, 
 
Cara Buskmiller, MD 
Principle Investigator, EASE-O 
 
Withdrawal Email 1 (for intervention arm, withdrawing during her detailed first 
trimester ultrasound) 
Dear [Name], 
 
We are sorry to see you go! Thank you for considering EASE-O, a randomized clinical 
trial to find out when is the best time for a detailed anatomy ultrasound in women with a 
BMI of 35 or greater. This email confirms that you have withdrawn from the study. Your 
data will not be analyzed and no further data will be collected. 
 
You do not have to do anything further, but we ask that you tell us about your experience 
during your ultrasound, at this link. Filling out this survey helps us understand what 
women like you prefer regarding their ultrasounds. We want to hear from you! 
 
Sincerely, 
 
Cara Buskmiller, MD 
Principle Investigator, EASE-O 
 
Withdrawal Email 2 (for intervention arm, withdrawing after her detailed first 
trimester ultrasound, before her safety second trimester ultrasound) 
Dear [Name], 
 
We are sorry to see you go! Thank you for participating in EASE-O, a randomized 
clinical trial to find out when is the best time for a detailed anatomy ultrasound in women 

IRB NUMBER: HSC-MS-20-0895 
  
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with a BMI of 35 or greater. This email confirms that you have withdrawn from the study. 
Your data will not be analyzed and no further data will be collected. 
 
You do not have to do anything further, but we encourage you to seek out an ultrasound 
between 18 and 22 weeks gestational age, if you haven’t already gotten one. You did 
have an ultrasound in the first trimester looking at all the baby’s parts, but these 
ultrasounds are still considered experimental (that’s why we are researching them)! You 
deserve a later ultrasound, it is still recommended and will be covered by your insurance 
as part of your routine prenatal care. 
 
Sincerely, 
 
Cara Buskmiller, MD 
Principle Investigator, EASE-O 
 
Withdrawal Email 3 (for comparison arm, withdrawing from study before detailed 
second trimester ultrasound) 
Dear [Name], 
 
We are sorry to see you go! Thank you for participating in EASE-O, a randomized 
clinical trial to find out when is the best time for a detailed anatomy ultrasound in women 
with a BMI of 35 or greater. This email confirms that you have withdrawn from the study. 
Your 
data will not be analyzed and no further data will be collected. 
 
You do not have to do anything further, but we encourage you to seek out an ultrasound 
between 18 and 22 weeks gestational age, if you haven’t already gotten one. The 
ultrasound you got in the first trimester was only to establish the dating of your 
pregnancy or check on the back of the baby’s neck, and didn’t look at all the baby’s body 
parts. A detailed ultrasound between 18 and 22 weeks recommended and will be 
covered by your insurance as part of your routine prenatal care. 
 
Sincerely, 
 
Cara Buskmiller, MD 
Principle Investigator, EASE-O 

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APPENDIX 4 
First Trimester Anatomy Ultrasound Protocol 
Initial survey: 
1. Document location of an intrauterine gestational sac (confirm not in prior 
hysterotomy or uterine isthmus) 
2. Document cardiac activity using M-mode 
3. Document fetal number and chorionicity if applicable 
4. Document placental position in relation to the cervical os (most previas are of no 
clinical significance) 
5. Document any subchorionic hemorrhage 
6. Biometry: 
a. Document CRL or 
b. Document HC, AC, BPD, and FL if greater than 11 weeks 
Planes: 
1. Midsagittal fetus. Landmarks required for optimal image: NT, nose, cord 
insertion, bladder 
2. Profile. Landmarks required for optimal image: NT, nasal bone, maxilla 
 
3. Transventricular plane. Landmarks required: bilateral symmetrical choroid 
plexus. 
 
4. Transthalamic plane. Landmarks required: bilateral thalami, falx cerebri 
between anterior horns of the lateral ventricle. 

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5. Transcerebellar plane. Required landmarks: bilateral thalami, fourth ventricle. 
 
6. Orbital plane. Required landmarks: bilateral orbits. 

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7. Facial plane. Required landmarks: bilateral orbits, bilateral maxillary processes. 
 
 
8. Four chamber view. Required landmarks: two ventricles, two atria in diastole. 

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9. Three-vessel-trachea view. Required landmarks: V-shaped aorta/PA with same 
directional flow, trachea. 
 
 
10. Coronal trunk. Required landmarks: stomach/diaphragm. 
11. Retroperitoneum. Required landmarks: bilateral kidneys 

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12. AC. Required landmarks: stomach, umbilical vein. 
13. Cord insert. Required landmarks: cord insertion with abdominal skin away from 
adjacent tissue 
14. 3VC. Required landmarks: bladder, bilateral umbilical arteries using Doppler. 

IRB NUMBER: HSC-MS-20-0895 
  
IRB APPROVAL DATE: 08/12/2021 
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15. Extremities. Can be captured by imaging bilateral arms/hands, then bilateral 
legs/feet, or by imaging the right extremities together and the left extremities 
together. Required landmarks: four upper and four lower limbs. Can also be 
captured in 3D. (Fingers and toes not required.) 

IRB NUMBER: HSC-MS-20-0895 
  
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IRB NUMBER: HSC-MS-20-0895 
  
IRB APPROVAL DATE: 08/12/2021 
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16. Spine. Required landmarks: entire spine with overlying skin not adjacent to any 
other structures. 
 
 
Additional planes: 
1. Assess maternal anatomy 

IRB NUMBER: HSC-MS-20-0895 
  
IRB APPROVAL DATE: 08/12/2021 
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2. Assess prior hysterotomy if applicable 
3. Obtain uterine artery doppler measurements 
4. Obtains subtraction imaging of amniotic fluid volume