Clinical trial NCT04253626
Conditions: Pregnancy Related Anemia, Iron Deficiency
Sponsor: Stanford University
Start date: 2021-01-21; Completion date: 2024-07-01
Enrollment: 83 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Evaluate the extent to which treatment of iron deficiency anemia beyond 24-34 weeks' gestation of pregnancy with intravenous iron increases hemoglobin compared to oral iron. The investigators will test the hypothesis that pregnant women who are anemic in the second and third trimester are more likely to significantly increase their hemoglobin with intravenous iron as opposed to the usual standard of care, oral iron.

Detailed description:

Arms: arm 1: Participants will receive 510mg intravenous iron ferumoxytol, with a maximum of 2 doses based on the baseline hemoglobin level. The ferumoxytol is administered as an infusion for approximately 15 - 30 minutes. arm 2: Participants will be prescribed 1-2 ferrous sulfate 325mg tablets by mouth (based on severity of anemia) until delivery. For standardization, the dosage is as follows based on severity: one ferrous sulfate tablet for women with baseline hemoglobin 9-11, and two ferrous sulfate tablets for hemoglobin \< 9.
Interventions: intervention 1: Ferumoxytol Injection [Feraheme] intervention 2: Ferrous Sulfate
Intervention descriptions: intervention 1: 510mg intravenous ferumoxytol intervention 2: 325mg oral ferrous sulfate

Protocol documents:
Prot_SAP_001.pdf: 
 
 
 
 
A Pilot Trial for the Prevention of Anemia in Pregnancy 
at Time of Birth Admission: 
A Randomized Clinical Trial 
 
National Clinical Trial (NCT) Identified Number: NCT04253626 
Principal Investigators: Irogue Igbinosa, Deirdre Lyell 
Research Coordinators: 
, 
 
Funded by: MCHRI 
Updated Feb 10 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
Prevention of Anemia in Pregnancy at Time of Birth Admission: A Randomized Clinical 
Trial 
Objective: Our goal is to provide evidence on the most effective treatment of persistent iron 
deficiency anemia (IDA) late in pregnancy among all women. Our aims are to evaluate the 1) 
mean change in hemoglobin in IV iron group vs oral iron over 4 weeks, and 2) the mean change 
in hemoglobin in the IV vs oral iron group pre-delivery  
Organization: Stanford University Maternal-Fetal Medicine Division  
Clinical Center: Stanford/LPCH OB clinic 
Design Type: Open Label Randomized clinical trial  
Inclusion Criteria:  
1. Pregnant patients 18 years old and above receiving prenatal care at Stanford/LPCH OB 
clinic 
a. Hemoglobin < 11 g/dL, serum ferritin < 30 ug/dL and or transferrin saturation 
(TSAT) < 20% 
b. Between 24-34 weeks’ pregnancy  
c.  (study will offer iron studies to determine eligibility for patients eligible by 
hemoglobin if labs not ordered by primary obstetrician/health care provider per 
standard of care) 
2. Singleton pregnancy 
3. Viable Pregnancy  
4. Hemodynamically stable 
Exclusion Criteria: 
1. Patients unable to give informed consent 
2. Known allergy/hypersensitivity to IV iron  
3. Inflammatory Bowel Disease or history of gastric bypass surgery 
4. Dialysis-dependent Chronic Kidney Disease 
5. Known Hemoglobinopathies such as sickle cell disease, beta- thalassemia, alpha 
thalassemia (not including trait)  
6. Folate/Vitamin B12 deficiency 
7. Known malignancy 
8. History of multiple medication allergies (> 2 allergies) 
9. Hemoglobin above 12 or less than 7 g/dL 
10. Patients with complex past medical histories which may include history of multiple 
medication allergies, connective tissue disorder, etc.  
11. Medication allergy to Tylenol 
12. Placenta previa  
Interventions:  
1. Active group: IV iron (ferumoxtyol) 
2. Standard group: Oral Ferrous sulfate 
Medications:  
Ferrous sulfate 325mg tablets every other day or 650mg (two 325mg tablets) po every other day 
per protocol 
Ferumoxytol intravenous iron – 510mg x1 dose or 510mg x2 doses per protocol 


 
 
 
 
Tylenol 650mg tablets (or 325mg tables x 2) 
Analysis: Intent to Treat 
Outcome Measures:  
Primary composite:  
o Correction of anemia by time of birth 
 Change in hemoglobin 
o Rates of blood transfusion postpartum  
Primary safety outcome:  
o Rates of adverse events 
o Compliance with medication 
o Severe neonatal composite morbidity 
o Severe maternal morbidity  
Timetable:  
Recruitment: 0-9 months 
Data Collection: 0-12 months 
Complete follow up: 0-16 months  
Final data/primary analysis: 12-16 months  
 
Sample size: 80  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
1.  INTRODUCTION 
This manual gives detailed instructions on procedures for the Prevention of Anemia in 
Pregnancy (PAP) Trial. It is meant to serve as a reference guide for study staff, including 
investigators, coordinators, study nurses, and data managers.  
 
1.1 Organizational Structure  
 
This study is governed by Stanford Maternal Fetal Medicine Division, Labor and Delivery, and 
the Clinical Translational and Research Unit site. 
 
1.1.1 Steering Committee (SC) 
 
A Maternal-Fetal Medicine Clinical Review Unit (CRU) and Data Safety Monitoring Board 
(DSMB) that brings together the multi-disciplinary will oversee implementation including: 
finalizing the clinical protocol, training and certification, monitoring recruitment, data 
coordination and quality control, DSMB recommendations and IRB-related issues. The SC will 
also make final decisions about data analysis and interpretation, secondary analyses, presentation 
at scientific meetings and publications.  
 
1.1.2 Responsibilities  
 
The responsibilities of these individuals are described briefly here:  
 
PI and co-PIs are responsible for ensuring the proper conduct of the study clinic site including 
recruitment as specified in the protocol and accurate collection of the data. 
Other specific duties include:  
 
a.  Obtaining and maintaining IRB approval and training for study personnel 
b.  Obtaining sufficient study areas for study personnel to interview patients and perform 
study procedures, including storage of study medication and other study supplies.  
c.  Participate in study- related meetings or conference calls 
d.  Familiarity and training for REDCap based data entry system by appropriate staff.  
e.  Screen potential participants for eligibility and consent them. It is important to ensure 
the patient’s primary obstetric provider agrees to follow the study treatment protocol 
during pregnancy.  
f.  Randomize per protocol to intervention arms – both arms to receive medication 
g.  Follow participants during the antepartum, delivery and 6 (4-12) weeks postpartum 
periods: with labs as indicated in the protocol and with pre- and post-intervention surveys 
to monitor patient symptoms and adverse effects 


 
 
 
 
h.  Facilitate collection of labs at 24-28 weeks gestation (preferred window, but may 
collect up to 34 complete weeks), labs at 4 and 8 weeks post-initiation of pill for standard 
group and post-treatment of intravenous iron in the active group and delivery. 
i.  Trained research staff will conduct research data abstraction from patient medical 
records, and conduct participant interviews, pill counts, and other direct participant 
contact as required by the protocol. Research staff at CTRU, will undergo training to 
ascertain response to severe adverse outcomes, specifically identification of 
hypersensitivity reactions to intravenous iron. 
j.  Investigators will participate in blinded review of outcomes in order to confirm the 
primary and other key outcomes.  
k. Maternal outcomes will be ascertained through 6 weeks including a postpartum visit in 
this window. If unscheduled visits occurred at another facility, obtain medical records 
release (if one has not already been obtained) to order hospital visit records.  
l.  All newborn outcomes will also be ascertained through 6 (4-12) weeks through 
medical records chart review. If unscheduled visits occurred at another facility, obtain 
medical records release (if one has not already been obtained) to order hospital visit 
records.  
m.  Data collection forms for maternal outcomes, newborn outcomes, NICU outcomes, 
and postpartum clinic/hospital outcomes will be completed by study personnel. These 
forms will be used to enter the clinical data into the study data base.  
 
The Study Coordinator will be responsible for the day-to-day operations of the study at the 
clinical center, including recruitment and data collection processes. This responsibility includes 
the following:  
a.  Establishing a method of training and monitoring to ensure primary obstetric providers 
are following the study treatment protocol during the pregnancy. 
b.  Establishing a method to ensure that all potential participants receive medications and 
appropriate follow up 
c. Establishing a method that for screening women with IDA who are potentially eligible 
for the study e.g. dedicated clinic days or sessions.  
d.  Assures that study drug is available at all times by checking the available drug supply 
at least weekly. The current workflow is that Stanford’s pharmacy will dispense 
medications with Stanford’s CTRU. 
e. Meeting with Stanford Investigational Drug Pharmacist pharmacy and/or site CTRU if 
necessary, to understand center specific drug request procedures.  
f. Arranging for the ordering and storage of study supplies.  
g.  Collecting maternal and neonatal information necessary to complete all study forms.  
h.  Will abstract information related to primary and other key outcomes, and assure that 
the PI and IRB (if required by institution) is notified of any primary outcome events and 
adverse events.  
i. Training additional staff as needed in data collection, forms completion and data entry.  
j. Coordinating data entry, including controlling access to the REDCap and study unit as 
applicable, and assuring that required back-up security and confidentiality procedures are 
maintained.  
k. Organizing and maintaining records, including the protocol, data forms, reports and 
correspondence 


 
 
 
 
 
1.2 Procedures for Participant Confidentiality 
 
 The REDCAP database will contain PHI linked to the patient’s clinical data. The MFM 
Research team members are the only one who will be able to access this database. A 
study/screening number will be used to identify each participant. Site will maintain a log of 
participant names and medical record numbers.  
 
1.3 Training and Site Initiation  
 
A training session for study coordinators will be held before recruitment starts. The purpose of 
the training workshop is to review the study design, objectives, procedures, data collection forms 
and a demonstration of the REDCap data base. The coordinators, in turn, are responsible for 
training any additional staff assigned to this study. Clinical site initiation to enroll and randomize 
participants is dependent upon completion of a series of preliminary tasks. These include 
completion of appropriate regulatory approvals (IRBs).  
 
Site staff training, certification, and receipt of all study supplies including medications will need 
to be completed as well as the development of a site recruitment plan. Fulfillment of the 
following are requirements before start of study:  
 
1. Review of the final version of the study protocol, data forms and manual, and study 
medications.  
2. IRB approval and consent forms on file at Stanford. Due to COVID, also consider e-consent 
process.  
3. Completion of training and data entry of forms.  
4. Training with Stanford’s CTRU  
 
1.4 IRB approval  
 
Approval by an IRB before any participant examination or data collection can begin. Once a 
study has been approved, any additional information about the study that relates to participant 
safety (i.e., protocol changes, significant adverse events, changes in the consent form) also needs 
to be submitted to the IRB.  
 
1.5 Interim IRB Review/Approval  
 
After initial approval, an IRB must be notified any time about:  
• Recruitment Brochures and Advertisements  
• Form Letters or Study information sent to participants 
• Protocol Amendments  
• Protocol Deviations  
• Serious Adverse Events (SAEs)  
• Unanticipated problems 
• Consent Form Revisions  
 


 
 
 
 
 
1.5.1 Protocol Amendments  
 
All protocol changes must be sent to an IRB as protocol amendments.  
 
1.5.2 Regulatory Binder  
 
The Study Regulatory Binder is the administrative binder that serves as the regulatory record of 
each clinic’s participation in the IDA study. It should be kept current and available for review by 
the DSMB or in the event of an audit. The binder should include current copies of: 
• Protocol and revisions 
• All protocol amendments  
• IRB submissions and approvals, IRB renewals and any submitted protocol deviations and 
log, IRB correspondence (adverse events reports)  
• Copies of IRB approved informed consent document(s)  
• Research participant advertisements, (e.g. patient brochures, pamphlets) patient education 
materials, newsletters, etc.  
• Current correspondences relating to human subjects research (may keep separate 
correspondence file)  
• Enrolled patient log with pertinent identifier information (randomization number if 
needed)  
• List of study drug formulary and package inserts  
 
Other items that may also be included are: recruitment plans, a set of study forms, CVs or 
biosketches for study staff, staff responsibility logs, essential elements of informed consent 
checklist, protocol deviation logs or other requirements from Stanford institution 
 
 
2.  STUDY INFORMATION 
 
 
2.1 Study Rationale  
Iron deficiency is the most common cause of anemia in pregnancy in the United States (Mei). 
Our study will add key evidence to improve the management of antepartum IDA in late 
pregnancy, when women are at particularly high risk for poor outcomes. Our study will also 
assess previously unstudied outcomes, notably blood transfusion. 
Rationale for change in intravenous iron  
The initial proposal aimed to conduct a prospective open label randomized clinical trial 
comparing standard of care (SOC) oral ferrous sulfate to IV FCM for the treatment of anemia in 
pregnancy. FCM was the IV iron formulation of choice based on a FER-ASAP clinical trial and 
meta-analysis supporting safety of iv irons in pregnancy 1–4. It also has required less time per 
infusion (30min) and max course of 2 doses. As highlighted by the reviewers, hypophosphatemia 
is an increasing concern noted in studies of nonpregnant populations5. Further review of previously 


 
 
 
 
existing study protocols shows that serum phosphate was not assessed in initial trials evaluating 
safety in pregnant women. Huang et al is the only study that reports the rate of hypophosphatemia 
in a cohort of 20 pregnant women, one of which developed clinically relevant hypophosphatemia. 
The expertise of Stanford faculty Dr. Chertow, a co-author in “Randomized Clinical trial of IV 
iron induced hypophosphatemia”, graciously provided further assistance and helped to 
contextualize previous research experience with CKD patients5. As a precaution, this study 
proposal has been significantly modified to exclude the use of FCM.  
2.2 Background  
Anemia in pregnancy is a risk factor for increased rates of maternal and perinatal morbidity 6. 
Antepartum anemia has been linked to higher rates of blood transfusion, preterm delivery, low 
Apgar scores, NICU admissions, and delay in neuro-cognitive motor development6,7. Iron 
deficiency represents over 70% of the anemias diagnosed in pregnancy. Other causes of anemia 
can include malnutrition, folate or vitamin B-12 deficiency, hemoglobinopathies, chronic 
infections and poor access to prenatal care8,9. This effect is further amplified in non-Hispanic 
Black, Mexican American pregnant women, and women with a history of greater than two prior 
births10. Black pregnant women often experience the highest rates of antepartum anemia, 
approximately two-to-threefold compared to other racial/ethnic groups 11. 
Physiologically, iron utilization increases from approximately 2 mg/day in the non-pregnant 
state to 5-6 mg/day in pregnancy 12. Furthermore, blood volume expansion by approximately 50% 
and the increase of plasma cell volume by 35% contribute to heightened consumption of iron stores 
with advancing gestation of pregnancy13. Current guidelines support supplementation with 27 mg 
of elemental iron in pregnancy, an equivalency commonly found in over the counter prenatal 
vitamins 9,14. Oral ferric salts (such as ferrous sulfate) are recommended for IDA in fractionated 
dosing of 100-200 mg of elemental iron/day15. Additional prescriptions for iron are influenced by 
laboratory assessments at the initiation of prenatal care and 24-28 weeks of pregnancy7. Oral 
preparations, although cheaper, are associated with adverse gastrointestinal side effects, 
noncompliance, and limited interval increase in hemoglobin at the time of delivery compared to 
intravenous preparations 16. A meta-analysis concluded greater than 70% of pregnant women 
experienced an adverse side effect, largely GI, with oral iron treatment and discontinuation of oral 
medication in approximately half of patients prescribed 17. 
Consequently, some women will require parenteral administration of iron. Newer preparations 
of intravenous iron solutions have been well-tolerated with low anaphylaxis type reactions and 
fewer adverse side effects than older formulations 3,4. Intravenous iron sucrose in pregnancy has 
been shown to be efficacious in addressing anemia in late pregnancy 3,18, yet drawbacks include 
dosing (max 200mg/dose), frequency (avg 4-5 infusions) and duration (1-2hrs each). The 
contemporary class of IV irons available in the U.S. include ferric carboxymaltose (FCM), 
ferumoxytol and low molecular weight dextran (LMWD). LMWD has the advantage of being 
administered in a single dose; yet requires a test dose is recommended prior to infusion and 
concerns regarding rates of anaphylaxis limited widespread use19. An investigation demonstrated 
that most of the severe adverse events were associated with its predecessor high molecular weight 
iron19. Ferumoxytol is a “superparamagnetic iron oxide” that creates an iron-carbohydrate complex 
with elemental iron that allows for more rapid infusion20. Ferumoxytol is FDA approved for adults 
with IDA20. Animal studies of ferumoxytol have not shown teratogenic effects at human doses; 
however, teratogenicity was seen in animal studies at levels six times that of human dosing20,21. 


 
 
 
 
As a precaution, IV irons are not recommended in the first trimester to decrease the possibility of 
harm during organogenesis. The FDA updated labelling for pregnancy and lactation considerations 
list consideration for IV iron use in second/third trimester of pregnancy and “it is not known if 
ferumoxytol changes breast milk concentrations.” A clinical trial with ferumoxytol in pregnancy 
is near completion with standard dosing (510mgx2 or single dose infusion)(clinical trials.gov) for 
all patients22. By comparison, our proposed trial recommends hemoglobin based dosing 
extrapolated from the Ganzoni formula23. Ferumoxytol safety data for anaphylaxis is less than < 
1%19,24.  
Our study will add key evidence to support the management of antepartum IDA in late 
pregnancy, when women are at particularly high risk for poor outcomes. In collaboration with the 
CMQCC (Medical Director Dr. Elliott Main, Co-I on this proposal), our study will also assess 
feasibility for a large scale, multicenter quality intervention for California hospitals.  
 
 
2.3 Risk/Benefit Assessment  
 
2.3.1 Known Potential Benefits  
 
Potential benefits of treatment with iron during pregnancy including repletion of iron stores and 
decreased incidence of SMM. This potential benefit may be increased in diverse racial/ethnic 
populations that experience higher rates of iron deficiency anemia. A 2013 meta-analysis 
suggested daily oral iron use could increase birth weight of infant, concerns in a follow-up study 
were raised about risk associated with over supplementation.  
Over supplementation is less likely to be a risk in this cohort as we correcting only iron 
deficiency anemia and not iron deficiency, it’s precursor.  
Iron crosses the placenta and is also thought to be beneficial for breastfed infants. A recent 
review did not reveal studies that suggest adverse effect of iron in breast milk.  
 
2.3.2 Assessment of potential risks  
 
Oral Iron Risks 
 
Pregnancies in experimental animals: Large-dose dietary iron supplements were not teratogenic 
when tested in mice and rats. However, pregnant rabbits fed maternally toxic dose levels of an 
iron supplement had offspring with an increased incidence of defects of the central nervous 
system and skeleton. Retrospective studies have raised concern of teratogenic effect of oral iron 
in the first trimester, however, the findings were not replicated in larger studies. Observational 
studies have not found an increase in congenital defects with oral iron use. 
 
Oral ferrous sulfate adverse effects include darkening of stools < 80%), abdominal pain (~70%), 
heartburn, nausea (68%), flatulence (38%), and diarrhea (23%).  
 
Note: Intentional severe iron intoxication is potentially fatal and has been associated with 
adverse fetal and maternal outcomes such as preterm birth, miscarriage. There have been reports 
of patient overdose of oral iron with use of desferoxamine if severe.  


 
 
 
 
 
Patients in this study will receive oral medication at interval lengths.  
 
Intravenous Ferumoxytol Risks 
 
IV iron is indicated in pregnant women who cannot tolerate oral iron, those with persistent anemia 
despite oral iron treatment and in pregnant women with impaired absorption 7. Ferumoxytol, is 
part of a newer class of IV irons that can be administered more quickly and have less adverse 
reactions due to a tighter binding of elemental iron by carbohydrate shells 25,26. As of 2018, 
Ferumoxytol is FDA approved for adults with IDA. Animal studies of ferumoxytol have not shown 
teratogenic effects at  human doses; teratogenicity was seen in animal studies at levels 4x that of 
human dosing20. IV iron transfusions are not administered in the first trimester due to concerns of 
this time period being the most critical for organogenesis. There are ongoing clinical trials with 
ferumoxytol in pregnancy near completion with standard dosing for all patients. Comparison 
studies of FCM to ferumoxytol have shown that ferumoxytol has a lower anaphylaxis rate and 
<1% hypophosphatemia27.  
 
Information adapted from package insert 
 
Black Box warning on label: “Serious hypersensitivity reactions, (some fatal), including 
anaphylaxis may occur, presenting with cardiac/cardiorespiratory arrest, clinically significant 
hypotension, syncope, or unresponsiveness even in patients who previously tolerated 
ferumoxytol. Infuse over ≥15 minutes and have equipment for resuscitation and trained 
personnel experienced in handling emergencies immediately available during use. Monitor 
patients for signs/symptoms of hypersensitivity reactions, including blood pressure and pulse 
during and ≥30 minutes (until clinically stable) following administration. Other hypersensitivity 
reactions have also occurred (pruritus, rash, urticaria, wheezing). Patients with multiple drug 
allergies may have greater risk of anaphylaxis; elderly patients with multiple or serious 
comorbidities who develop hypersensitivity and/or hypotension after ferumoxytol may be at 
greater risk for serious adverse events.”   
Fatal and serious hypersensitivity reactions including anaphylaxis have occurred in patients 
receiving ferumoxytol in less than 1%. Initial symptoms may include hypotension, syncope. 
Unresponsiveness, cardiac/cardiorespiratory arrest.  
Hypersensitivity reactions have occurred in patients in whom a previous ferumoxytol dose was 
tolerated. Other adverse reactions potentially associated with hypersensitivity have occurred 
(pruritus, rash, urticarial reaction and wheezing). Patients with a history of multiple drug 
allergies may have a greater risk of anaphylaxis with parenteral iron products.  
Excessive therapy with parenteral iron can lead to excess storage of iron with the possibility of 
iatrogenic hemosiderosis.  
Administration of ferumoxytol may transiently affect the diagnostic ability of magnetic 
resonance imaging. Alteration of MR imaging studies may persist for up to 3 months following 
the last ferumoxytol dose. The most common serious AEs reported in ferumoxytol-treated 


 
 
 
 
patients were syncope, gastroenteritis, seizure, pneumonia, hemorrhagic anemia, and acute 
kidney injury.  
A separate protocol is referenced below for the management of hypersensitivity reactions.  
IV ferumoxytol in pregnancy  
Ferumoxytol is a “superparamagnetic iron oxide” that creates an iron-carbohydrate complex with 
elemental iron that allows for more rapid infusion20. Ferumoxytol is FDA approved for adults 
with IDA20.  
• Animal Studies 
Animal studies of ferumoxytol have not shown teratogenic effects at human doses; however, 
teratogenicity was seen in animal studies at levels six times that of human dosing20,21. As a 
precaution, IV irons are not recommended in the first trimester to decrease the possibility of 
harm during organogenesis.  
• FDA label for pregnancy  
The FDA updated labelling for pregnancy and lactation considerations list consideration for 
IV iron use in second/third trimester of pregnancy and “it is not known if ferumoxytol 
changes breast milk concentrations.”  
• Studies in Pregnancy 
A clinical trial with ferumoxytol in pregnancy is near completion with standard dosing 
(510mgx2 or single dose infusion)(clinical trials.gov) for all patients22 
 
Safety measures for this study include the following:  
- 
Obtain VITALS prior to transfusion (see table below) for reference range in 
pregnancy 
- 
Monitor patients for signs and symptoms of hypersensitivity during and after IV iron 
administration for at least 30 minutes and until clinically stable following completion 
of the infusion. IV iron will only to be administered in sites where personnel and 
therapies are immediately available for the treatment of serious hypersensitivity 
reactions.  
- 
Pregnant women in this study may receive up to a maximum dose of 1020mg 
ferumoxytol only; this is the max dose per course as outlined by the package label 
instructions. Each dose will be given as 510 mg IV infusion and if needed, a second 
dose of 510 mg ferumoxytol may be given 3-8 days after first infusion. 
- 
Monitor patients for signs and symptoms of hypertension following each ferumoxytol 
administration. 
 
 


 
 
 
 
 
Source: Williams Obstetrics and Gynecology, 25th Edition 
 
Vital signs which suggest hemodynamic instability  
- 
HR > 120  
- 
Systolic Blood Pressure > 160 or Diastolic Blood Pressure > 110  
• (pts with controlled hypertension can be enrolled in the study) 
- 
RR > 24 or less than < 10 
 
*See Separate Section for management of adverse reactions  
 
Oral Acetaminophen Risks 
 
Acetaminophen is generally considered to be safe to use during pregnancy and has been 
categorized as Class B for all trimesters. Acetaminophen is known to cross the placenta during 
pregnancy, and acetaminophen administered during labor has been found in the umbilical cord 
blood at delivery (Levy 1975). There is no known association with teratogenicity, however few 
clinical studies have assessed safety (Collins 1981). More recent studies with poor power have 
suggested a link between prenatal acetaminophen use and asthma, lower intelligence quotient, 


 
 
 
 
shorter male anogenital distance (predicting poor male reproductive potential), attention-
deficit/hyperactivity disorder, poorer attention and executive function, and behavioral problems 
in childhood (Toda 2017). The Society of Maternal Fetal Medicine deems these studies as 
inconclusive as the methodologies were subject to recall bias and no data on dosing or frequency 
of use was incorporated into the analyses (Society of Maternal Fetal Medicine 2017). Thus, the 
current recommendation is to use acetaminophen for at the lowest dose for the minimal duration 
possible. We will be administering a single 650mg dose of acetaminophen in the course of this 
study, which is considered to be safe in pregnancy.      
 
Adverse effects of oral acetaminophen include nausea, vomiting, abdominal pain, loss of 
appetite, itching, rash, headache, dark urine, clay-colored stools, or jaundice. Serious allergic 
reactions to acetaminophen can include rash, itching/swelling (including of the 
face/tongue/throat), severe dizziness, or difficulty breathing. 
 
2.3.3 Risk Benefit/Ratio 
 
Iron deficiency anemia at admission for birth hospitalization has been associated with increased 
severe maternal morbidity, preterm birth, low birth weight, incidence of C-section and more. 
Assessment of outcomes in this study will determine how treatment can improve maternal and 
neonatal outcomes. 
 
3. OBJECTIVES 
 
3.1 Primary Outcome  
 
Perform a pilot randomized control trial of oral ferrous sulfate to IV ferumoxytol in 
women with IDA in the second and third trimester of pregnancy. We will test the hypotheses 
that 1) intravenous (IV) iron therapy will increase hemoglobin more with IV iron than oral iron 
over a 4 week period, approximately 0.8 g/dL in the IV group and 0.5g/dL in the oral arm16,28 
and 2) IV iron will improve anemia at the time of birth admission, 1.5 g/dL for IV iron and 1 
g/dL for oral iron supplementation, the standard of care28,29 
 
3.2 Secondary Outcome  
 
Evaluate the  
- 
rate of patients who discontinued treatment, 
- 
the rate of adverse events associated with treatment,  
- 
the need for blood transfusion postpartum 
- 
symptoms of patients before, during, and at the completion of therapy 
 
 


 
 
 
 
4.  STUDY DESIGN 
 
4.1 Overall Design  
This will be an open-label randomized clinical trial at an academic tertiary care center comparing 
oral ferrous sulfate to intravenous (IV) ferumoxytol in pregnant women with IDA in the second 
or third trimester.   
 
4.2 Justification for Dose  
 
Historically, oral ferrous sulfate has been increased up to 2-3 tablets daily for anemia. However, 
this practice as come into question as women often have difficulty with completing oral 
treatment due to gastrointestinal side effects. Immediate release oral iron products are preferred 
for treatment of iron deficiency anemia; enteric coated and slow/sustained release preparations 
are not desired due to poor absorption (Hershko 2014; Liu 2012). 
 
Further, there is increasingly more and more evidence optimal oral iron absorption occurs with 
single dosing every other day (Stoffel, et al 2020). There is also evidence to demonstrate 
intermittent dosing is also associated with less adverse side effects (RR 0.41, 95% CI 0.21 to 
0.82; 6 studies, 1166 participants; moderate‐quality evidence) (Cochrane 2019). 
 
The dosing for intravenous iron was initially based on the Ganzoni formula. However, it was 
noted to be cumbersome as it was not practical to dose outside of the confines of elemental iron 
in the viable. Thus in clinical practice patients have received the standard dosing 510 mg x  2 and 
recently there was an investigation by Auerbach et al which demonstrated the efficacy of single 
dosing of 1020 mg in a single infusion (MA).  
 
In regards to a pregnancy specific population, it is of particular interest if receipt of intravenous 
doing can be stratified by hemoglobin level ranges. There is retrospective data that suggests that 
intravenous iron dosing with respect to pre-pregnancy body mass index may also be an area of 
future concern.  
 
 
4.3 End of Study Definition  
 
The study will be complete once enrollment has been completed. The goal is 80 patients with 40 
in each arm.  
 
4.4 Sample Size  
 
We estimated minimum sample size required for 90% power, one-sided α=0.025, and estimated 
effect sizes for the outcomes of change in proportion of women (Hg <11g/dL) by birth 
hospitalization based on the findings of previous studies16,30. Based on these parameters and 
allowing for 20% drop-out rate, the study requires 32 subjects per arm. The analysis plan and 
sample size calculation were developed in consultation with Maternal-Fetal Medicine Senior 


 
 
 
 
Biostatistician, Stephanie Leonard, PhD (Co-I). We plan to recruit 80 patients to account for 
potential loss to follow up. 
 
4.5 Timeline  
 
Aim 1 Milestones 
Q1 Q2 Q3 Q4 
Extramural funding application preparation and submission. Letter of intent submitted 
to PCORI February 4th; full applications due May 5th.  
X 
  
  
  
Patient screening and enrollment. Patients identified via CBC testing during the 
second trimester 
X 
Randomization. Patients randomized to IV iron cohort or Oral iron cohort 
X 
 
 
 
Intervention. IV iron cohort receives intravenous iron. Oral iron cohort prescribed 
ferrous sulfate tablets.  
X 
X 
Data Analysis and Manuscript Preparation and Submission. 
X 
X 
 
 
5.  STUDY POPULATION 
 
5.1. Screening and Inclusion/Exclusion Criteria  
General Screening guidelines  
 
I. 
We will recruit Stanford Children’s Health prenatal patients via screening by second 
trimester complete blood count results, which are routinely performed to screen for 
anemia performed at 24-28 weeks’ gestation or may be performed for any other 
clinical indication, and with plans for delivery at LPCH. Patients can be included in 
the study up until 34 weeks.  
a. Patients will be eligible for the study if they meet the following criteria for IDA: 
hemoglobin 7-10.9 g/dL and serum ferritin <30 μg/L) (WHO).  
b. Patients on prenatal supplements with iron and/or taking oral iron in the early part 
of pregnancy but meeting other inclusion criteria will also be included in the 
study cohort.  
 
II. 
Patients will be screened by chart review  
a. Patients will need to complete iron studies to appropriately determine eligibility 
b. Data obtained from the screening process includes a review of CBC screening at 
performed in the second trimester.    
c. Review will also include pregnancy dating information using the initial 
ultrasound, and other medical history information taken at the first prenatal visits. 
Other baseline information, including such items as contact information, vitals, 
demographic and pregnancy history information, concomitant medications, and 
lifestyle information will be reviewed to assess suitability for study participation.  


 
 
 
 
d. Gestational age must be validated prior to enrollment using the latest ACOG 
criteria that compares LMP derived gestational age with ultrasound parameters. 
The ACOG criteria for gestational age determination are listed in section is as 
follows:  
 
 Gestational age assessment by ultrasonography in the first part of the second trimester 
(between 14 0/7 weeks and 21 6/7 weeks of gestation, inclusive) is based on a composite 
of fetal biometric measurements and has an accuracy of ± 7–10 days.  
 
5.2 Inclusion Criteria  
 
Women with a singleton, viable pregnancy greater than 24 weeks gestation based on the best 
clinical estimate according to ACOG criteria (see below) and have hemoglobin from 7-10.9 g/dL 
and serum ferritin < 30 ug.  
 
In agreement with ACOG, we recommend that all pregnant women be screened for anemia at the 
initiation of prenatal care and second/third trimester with a CBC. As this study is focused on 
intervention in the >24 weeks gestation, we will not be proposing a treatment regimen with IDA 
identified prior to this time.  
 
Ferritin is also an acute phase reactant and can be elevated in chronic illnesses. Therefore, the 
study would also include of women with a hemoglobin 7-10.9 g.dL and transferrin saturation < 
20%.  
 
5.3 Exclusion Criteria  
 
If the basic screening criteria are met (patient has IDA by parameters outlined above), the next 
step is to review the exclusion criteria. Those without exclusions should be approached for study 
participation.  
 
Assess the following exclusions:  
1. History of hypersensitivity to intravenous iron. Out of an abundance of caution, pregnant 
women with this history will be excluded due to concern for increased risk of anaphylaxis  
2. Known hemoglobinopathies. This was added as an exclusion criteria to remove the 
potential confounder that women with hemoglobinopathies such as sickle cell disease, 
thalassemia, may have a different physiologic response to intravenous iron.  
3. History of Inflammatory Bowel Disease or history of gastric bypass surgery. Intravenous 
iron is the first line for treatment of iron deficiency anemia in individuals with 
inflammatory bowel disease due to concerns for impaired absorption of oral iron.  
4. History of Dialysis-Dependent Chronic Kidney Disease (CKD). This category was added 
as patients with dialysis-dependent chronic kidney disease, because while the initial 
studies treated CKD patients with Ferumoxytol, these patients would require a complex 
dose adjustment due to decreased clearance.  
5.  Multifetal pregnancy (twins reduced to singleton or with vanishing twin syndrome prior 
to 14 weeks qualify)  
6. Gestational age < 24 weeks (needs ultrasound confirmation)  


 
 
 
 
7. High-risk co-morbidities for which treatment may be indicated: if patient with multiple 
medical problems important to discuss with primary obstetrician prior to enrollment.  
8. Pt with history of with two or more medication allergies: patient with history of medical 
allergies can slightly increase the risk of hypersensitivity reactions.   
9. Severe asthma or eczema 
10. Pt with the following will need additional review of medical history prior to inclusion:  
a. Receiving treatment with beta blockers 
b. Systemic inflammatory disease (rheumatoid arthritis, lupus) or connective tissue 
disorder 
c. Severe anxiety  
11. Medication allergy to Tylenol 
12. Placenta previa  
 
Women who meet inclusion criteria and do not have exclusion criteria may be approached 
for the informed consent process.  
 
 
5.4 Screening/Re-screening 
 
Patients may be included in the study up to 34 weeks 6/7 days. If the above inclusion criteria are 
met and exclusion criteria are absent, patients should be approached for study participation (if 
not already done) and randomization. All women who have a diagnosis of IDA should have the 
screening form initiated. The screening number will be generated electronically with REDCap is 
accessed and participant information is entered.  
 
5.5 Gestational Age Determination  
 
Gestational age will be determined by the most recent ACOG criteria with ultrasound required 
prior to randomization. If no ultrasound examination has been performed previously, one will be 
performed before the patient is randomized. Only pregnant women with gestational age > 24 
0/7 weeks will be included.  
 
5.6 Informed Consent Process  
 
An informed consent must be obtained before entry into the randomized trial. Full disclosure of 
the nature and potential risks of participating in the trial including the risks of being in the 
standard care group will be made. All potential participants will undergo the informed consent 
process as approved by the Institutional Review Board at each participating center. Any woman 
who is potentially eligible will be told about the study and asked if she is willing to participate. 
The point in the screening process at which a signed informed consent is required will be prior 
randomization. The study personnel conducting the informed consent process should emphasize 
the following study criteria during the informed consent process:  
 
• Patients eligible based on hemoglobin will be offered iron studies if it’s not already 
collected as part of routine prenatal care.  


 
 
 
 
• Randomization to a treatment arm with iron to increase hemoglobin, with 50% chance to 
be assigned to either arm: 
o One group will receive oral iron 
o One group will receive intravenous iron  
 
• Participants to sign medical release 
• American College of Obstetrics and Gynecology recommends oral iron as standard of 
care and IV iron only for a select few medical indications  
• Labs will be drawn 4 and 8 weeks post-initiation (Oral iron)/ post treatment (IV iron) and 
to evaluate anemia 
o Update: We will no longer perform study draw at 6 weeks postpartum, however, 
we will document labs performed as part of routine study care postpartum.  
• Follow up to occur at clinic appointments or phone/email to evaluate symptoms 
associated with either treatment 
 
Due to elevated rate of anemia in the Hispanic/Latinx/Latina population we will also have 
consents available in Spanish, or translators will be available for the consent process. A short 
form consent may also be used depending on the participant’s preferred language. 
 
All women who are considered for participation in the study (consent, decline or ineligible) 
should have a data entry form and entered into the electronic data system even if not randomized. 
Women who do not meet IDA criteria at 24-28 weeks screening visit, may be re-screened until 
such time that they meet exclusion criteria or they reach 34weeks’ gestation. 
 
5.7 Requesting Medical Release Forms  
 
In order to obtain medical records from participants, each participant should sign a “Release of 
Medical Information” form. A signed Release of Medical Information form should be obtained at 
the time of, and preferably before, randomization. Clinical Site staff will be able to answer any 
questions about the procedure at the very beginning of their participation in the study. Also, 
reluctance to supply medical records may serve as a potential “red flag” that a potential 
participant may be an adherence or retention risk.  
 If a participant refuses to sign a Medical Release Form, probe for reasons for the refusal. 
Explain the importance of the records for the study and why they are needed. Some participants 
may be willing to sign a release that is specific to information needed for a particular outcome. If 
the participant continues to refuse, note the refusal in the participant’s chart and continue to 
follow them according to the protocol if they consent to contacts and/or visits. 
 
5.8 Background and Rationale for Hemoglobin, Serum Ferritin and Transferrin Saturation 
Cutoffs  
In women without comorbidities, a serum ferritin <30 ng/mL can confirm the diagnosis of iron 
deficiency; levels ≥30 ng/mL rule out the possibility of IDA. Borderline levels of serum ferritin 
may be in the range of 30 to 40 ng/mL with chronic illnesses such as diabetes because ferritin is 
an acute phase reactant.  


 
 
 
 
We will also test for iron studies including ferritin, serum iron, total iron binding capacity 
(TIBC), and calculation of transferrin saturation (TSAT) if not already collected by primary OB 
prior to inclusion in study. 
TSAT below 20 percent can also demonstrate evidence of iron deficiency whether the ferritin 
level is low or normal. Iron supplements can falsely elevate the TSAT. To avoid this test 
interference, iron parameters should be drawn after an overnight fast, or the woman should 
simply be advised to avoid iron-containing foods or supplements to mitigate otherwise falsely 
elevated TSAT values.  
5.9 Frequency of Labs  
 
The timing of follow up labs is determined by the expected amount of time a participant should 
see an increase in hemoglobin. The hypothesis is that 1) intravenous (IV) iron therapy will 
increase hemoglobin more with IV iron than oral iron over a 4 week period, approximately 0.8 
g/dL in the IV group and 0.5g/dL in the oral arm16,28 and 2) IV iron will improve anemia at the 
time of birth admission, 1.5 g/dL for IV iron and 1 g/dL for oral iron supplementation, the 
standard of care28,29The estimates are informed from a  2018 study which reflected a 1.5 g/dL 
increase in hemoglobin by time of  delivery in the intravenous group.28 
 
The follow up and reassessment is further informed by Micheal Auerbach’s et al approach to 
treatment of IDA in pregnancy.  
 
 
6. RANDOMIZATION AND BASELINE VISIT PROCEDURES 
 
In participants with IDA prior to 24 weeks’ gestation, they can still be included in the study if 
they meet the inclusion criteria at 24 weeks gestation/ enrollment time frame. If IDA is a new 
diagnosis at the time of 24-28 weeks gestation, patients meeting the inclusion criteria be 
included.  
 
In both groups, prenatal data will be obtained at the randomization visit. The randomization visit 
should occur with timing of lab results availability and prenatal visit if applicable.  
 
Randomization may occur upon confirmation that all exclusion/inclusion criteria are satisfied 
and after verification of participant consent and HIPAA authorization. Of particular importance, 
careful consideration will be given the patient’s prior history and medications to determine final 
eligibility and the appropriate study algorithm to follow (see below). Study staff will also verify 
participant contact information and obtain a Release of Information. 
 
The MFM Research team will review the following before randomization:  
 
• Complete review of all exclusion and inclusion criteria  
• Informed consent obtained  
• Iron studies and baseline labs to confirm eligibility 
• Pre-intervention survey to assess symptoms 
 


 
 
 
 
After randomization: 
 
• Provide medication and instructions based on the treatment arm randomized to 
• Provide the group algorithm to both patient and provider. 
 
Once the participant is randomized, the treatment algorithms will be conspicuously placed in the 
patient’s medical record (whether electronic or paper medical record is utilized) such that 
providers will be aware of treatment plan at all times.  
 
In both groups, serial CBC follow up and survey for symptoms will be assessed.  Baseline data 
consisting gestational age of pregnancy, body mass index, pre-pregnancy weight and other 
prenatal data including baseline BP at the randomization visit will be included.  
Patients will be assigned to treatment groups by a concealed randomization allocation sequence 
using REDCap.  
 
The categories of patients randomized:  
 
Patients consenting to the study will be randomized 1:1 to two treatment groups  
 
Group 1: Patients randomized to the IV iron group will receive treatment as follows: 
- 
Women with Hgb 9-10.9 g/dL will receive one dose of 510 mg IV 
ferumoxytol  
- 
Women with Hg 7-8.9 d/dL will receive two doses of ferumoxytol 510 mg 
3-8 days apart for a maximum of dose of 1020 mg (see Figure 2). 
- 
Patients will receive 650mg of Tylenol prior to initiation of the infusion 
- 
The ferumoxytol is administered as an infusion for approximately 15-30 
minutes. Patients will receive the IV iron at Stanford’s Clinical and 
Translational Research Unit (CTRU) outpatient clinics with vitals 
collected before infusion and monitoring for 30minutes after infusion. 
Alternatively, patients who are admitted to the antepartum unit may 
receive the infusion inpatient.  
For the IV iron group, follow up labs will be performed at 4 and 8 weeks 
after completion of infusion/s;  
 
Group 2: The standard of care oral iron group will be prescribed 1-2 ferrous sulfate 325 mg 
tablets to be taken by mouth every other day until delivery. Dosage will be as follows for 
standardization: 
- 
one ferrous sulfate tablet every other day if Hg 9-10.9 g/dL, and  
- 
two tablets once every other day if Hg 7-8.9 g/dL.  
- 
Oral medications will be dispensed by the CTRU or by the Outpatient 
Investigational Pharmacy (final confirmation pending contracts) 
- 
Follow up labs will be drawn for both groups. For the oral iron group, it 
will be drawn 4- and 8-weeks post initiation of treatment  
Patients in both groups will complete post-intervention surveys at 1 week, 4 weeks, and 8-12 
weeks after initiating therapy to monitor symptoms and adverse events.  
 


 
 
 
 
6.1 Informed Consent  
 
No study activities will be conducted until an IRB approval is obtained. Potential participants 
who may be eligible will be approached by the research staff. The research staff will only 
introduce the study with the patients after a member of the clinical care team acquires permission 
from the potential participant that they can be approached for a study. If interested, the research 
staff will discuss the study and obtain an informed consent from the participant. 
 
Sufficient time will be given to participants to read the consent form, and to ask questions to 
ensure understanding. 
 
An IRB-approved study brochure may be given to potential participants to provide more 
information about the study and the procedures involved. 
 
6.2 Randomization visit: Study Groups  
 
There will be 2 intervention groups, active treatment or standard care, based on randomization. 
 
Group 1 (active treatment):  
 
The starting dose and escalation of therapy in the active treatment arm are as follows:  
 
Ferumoxytol: The patient will receive infusions at the Stanford’s CTRU or in the Antepartum 
Unit 
 
Ferumoxytol will be administered to participants with iron deficiency anemia with inclusion 
criteria as outlined above. Each single use vial contains 510 mg elemental iron / 15 mL.  
 
Prior to infusion of ferumoxytol, patients will receive 650mg of Tylenol.  
 
Participants with Hemoglobin between 9-10.9 g/dL will receive one dose of ferumoxytol 
(510mg). Participants with Hemoglobin between 7-8.9 g/dL will receive two doses (total 
1020mg) of ferumoxytol with 3-8 days interval between doses per manufacturer instructions. 
The IV iron is administered as an infusion for approximately 15 – 30 minutes. Patients will 
receive the IV iron at Stanford’s Clinical and Translational Research Unit (CTRU) outpatient 
clinics under the administration under trained Advanced Practitioner Provider/Research Clinic 
Nurse coordinator or in the inpatient Antepartum Unit. When administered via infusion, 
administer diluted as a slow IV infusion over at least 15 minutes. Patient should be in a reclined 
or semi-reclined position during the infusion; monitor for signs of hypersensitivity (including 
blood pressure and pulse) for at least 30 minutes after infusion. In the case hypersensitivity or 
side effects to medication, patients will be treated according to standard clinical guidelines, 
which may include administering Benadryl, Zofran, steroids, albuterol nebulizer, and in the cases 
of serious hypersensitivity, intramuscular epinephrine.   
 


 
 
 
 
Note: Serious hypersensitivity reactions have been observed with rapid IV injection (<1 minute) 
(Macdougall 2014; Vadhan-Raj 2014). Wait ≥30 minutes between administration of ferumoxytol 
and other agents that may cause serious hypersensitivity reactions and/or hypotension (e.g., 
chemotherapy, monoclonal antibodies). 
 
Group 2 (standard of care):  
Ferrous sulfate: the patient will receive a bottle dispensed with 100 pills at a time.  
 
Oral ferrous sulfate will be administered to participants identified with iron deficiency anemia as 
described above. One tablet every other day in patients with hemoglobin 9-10.9 g/dL and two 
tablets every other day will be provided for patients with hemoglobin levels between 7- 8.9 g/dL.  
 
Tablet: 325 mg [elemental iron 65 mg].  
 
6.3. Starting dose of Medications  
 
Historically, suggested dosing of oral ferrous sulfate has been increased in frequency up to 2-3 
times per day for treatment of anemia. However, this practice has come into question as women 
often have difficulty with completing oral treatment due to gastrointestinal side effects. 
Immediate release oral iron products are preferred for treatment of iron deficiency anemia; 
enteric coated and slow/sustained release preparations are not desired due to poor absorption 
(Hershko 2014; Liu 2012). Moreover, hepcidin has been found to be elevated immediately after 
taking oral iron, transiently decreasing absorption (Moretti 2015). A recent open-label, 
randomized controlled trials showed higher amounts of iron absorption with dosing every other 
day compared two daily dosing, with subsequent studies showing similar findings (Stoffel et. al., 
2017). Thus, oral iron with be dosed every other day in this study.  
 
The dosing for intravenous iron was initially based on the Ganzoni formula. However, it was 
noted to be cumbersome as it was not practical to dose outside of the confines of elemental iron 
in the viable. Thus, in clinical practice patients have received the standard dosing 510mgx2 and 
recently there was an investigation by Auerbach et al which demonstrated the efficacy of single 
dosing of 1020mg in a single infusion (MA).  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Algorithm A: Randomization  
 


routine CBC 24-
28 weeks
Hg<11, serum ferritin < 30 and or transferrin 
saturation < 20%
Randomization to 
Oral/IV iron arm
See text for full Exclusion 
criteria 
Hg < 7
excluded from trial, 
referral to 
hematology
Hg 7-8.9
Oral: two ferrous 
sulfate 325mg tablets 
by mouth daily
IV: Ferumoxytol 
510mg x 2
Hg 9-10.9
Oral: one ferrous 
sulfate 325mg daily
IV: Ferumoxytol 
510mgx1


 
 
 
 
7.  POST RANDOMIZATION VISITS AND MANAGEMENT OF IDA  
 
7.1 Post Randomization Visits and management of IDA for both groups at 4 weeks 
 
Group 1: (IV iron) Follow up visits 
Important for patient to maintain prenatal care, beyond 28 weeks gestation: frequency of visits 
determined by primary OB, this is often every 1-2 weeks  
- 
4 weeks post treatment labs to be timed with prenatal visit if possible. The 
CTRU is conveniently located adjacent to Stanford/LPCH OB clinic  
• if less than starting hemoglobin, then refer to hematologist  
 
Group 2: (oral iron)  
- 
4 weeks post-initiation labs to be timed with prenatal care where possible 
- 
Pill count to occur with CTRU or MFM research staff to assess 
compliance 
• If compliance a concern, assess reasons why 
 
 
In both groups, patient will complete a survey monitoring symptoms and adverse effects. 
 
7.2 Post Randomization Visits and management of IDA for both groups at 8 weeks 
 
Group 1: (IV iron) Follow up visits 
Important for patient to maintain prenatal care, beyond 28 weeks gestation: frequency this is 
often every 1-2 weeks  
- 
8 weeks post-completion treatment labs to be timed with prenatal visit if 
possible. The CTRU is conveniently located adjacent to Stanford/LPCH 
OB clinic  
 
Group 2: (oral iron)  
- 
8 weeks post-initiation labs to be timed with prenatal care where possible 
- 
Pill count to occur with CTRU or MFM research staff to assess 
compliance 
• If compliance a concern, assess reasons why 
 
In both groups, patient will complete a survey monitoring symptoms and adverse effects between 
8-12 weeks after initiation of therapy. 
 
 
 
 
 
 
 
 
 


 
 
 
 
Algorithm B: Eval for labs post 4 weeks treatment 
 
 
 
 
 
* Oral arm: if patients state they are intolerant to oral iron at any time during the study – 
refer to OB to discuss alternative treatment options 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC, iron studies 4 weeks post treatment
Oral Iron Arm*
Hg rise > 0.5 : continue oral iron
Hg rise < 0.5 g/dL 
repeat iron indices
If Hg< 7g/dl: Primary OB refer to 
Heme
Hg 9-11: continue
Hg 7-9: consider increasing dose 
of oral iron or Heme referral
IV Iron Arm 
Hg rise > 0.5: no additional 
medication
Hg rise < 0.5 g/dL, repeat iron 
indices
Hg 9-11: no additional action
Hg 7-9: if iron studies less than 
enrollment levels, consider 
heme referral
Hg < 7: Primary OB refer 
toHeme


 
 
 
 
 
 
 
Algorithm C: Evaluation of Labs 8 weeks post treatment  
 
 
 
 
 
 
 
 
 
 
 
*Oral arm: if patients state they are intolerant to oral iron at any time during the study – 
refer to OB to discuss alternative treatment options 
 
 
 
 
 
8 weeks post treatment
Oral Iron ARM*
•Hg rise > 1g/dL : continue oral iron
•Hg rise < 1 g/dL; repeat iron 
studies
•Hg 9-11: continue oral iron
•Hg 7-9: increase oral iron tablets  
or POB referral to Heme
•Hg < 7: POB referral to Heme
IV Iron ARM 
•Hg rise > 1 g/dL: no additional 
action
•Hg rise < 1 g/dL: repeat iron 
studies 
•Hg 7-11: no additional action
•Hg < 7: POB referral to Heme


 
 
 
 
 
 
7.3 Management of patient’s intolerance to study intervention 
 
Oral iron:  
 
For adverse effects, particularly GI, consideration may be given for IV iron as this is standard of 
care. Per ACOG, intravenous iron is an approved indication for patient’s intolerant of oral iron.  
 
Intravenous iron: 
 
For adverse effects such as hypotension (maternal BP˂90/60) and persistent dizziness, 
headaches, lightheadedness or fatigue and no other potential cause other than the medication, 
will be assessed for adverse reactions and any signs of anaphylaxis. Methylprednisolone, 
solumedrol, or dexamethasone, albuterol nebulizers, and intramuscular epinephrine will be 
available on site for any immediate concerns. 
 
PLEASE REFER TO THE DETAILED ALGORTIHM APPROACH FOR MANAGEMENT 
OF ADVERSE REACTIONS: this is a figure from Rampton, et a “Hypersensitivity reactions to 
intravenous iron: guidance for risk minimization and management.”  
 
For patients that are stable for transfer, the plan will be for obstetric monitoring and further 
evaluation at the LPCH OB triage on the third floor. The location is across the street from the 
CTRU and Stanford/LPCH clinic. The patients will still be followed by the study in intent to 
treat fashion. In the cases of an unstable patient, 911 will be called and patient will be transferred 
immediately to the emergency room.  
 
To increase effective management of possible hypersensitivity reactions in the IV group: the 
following have been included.  
- 
Reference range of normal vitals in pregnancy 
- 
Algorithm for management of hypersensitivity reactions  
 
 
 


 
 
 
 
 
I. 
Management of mild Hypersensitivity reactions 
II. 
Mild of Moderate Hypersensitivity reactions 
III. 
Severe/life threatening Hypersensitivity reactions  
 
 
Note: Methyl prednisone prior to IV infusion may considered on case by case basis for patients 
with history of asthma or high risk medication allergy.  
 
 
 
 
 
 


 
 
 
 
 
7.4 Study Procedures by Visit  
 
 
Research staff trained in obstetric and perinatal outcomes abstraction will be responsible for 
research data abstraction from patient medical records. Outcomes will be ascertained until 
delivery and maternal/infant discharge and up to 6 (4-12) weeks postpartum depending on the 
outcome.  
 
 
7.5 Management of Unscheduled Visits  
 
To facilitate appropriate management of study participants during unscheduled visits, we will: 
Visit Description 
Screening/ 
Enrollment 
Treatment 
4 weeks  
Post-initiation/ 
Post-
completion 
8 weeks   
Post-initiation/ 
Post- 
completion 
Delivery 
1 day 
Postpartum 
6 weeks 
postpartum  
IV 
Ferumoxytol 
Oral  
Ferrous 
sulfate 
Visit Window 
24-34 weeks 
GA 
24-34 weeks 
24-34 
weeks GA 
up to 
delivery 
 
 
 
1 day after 
delivery 
 
Screening of pregnant women with 
eligible hemoglobin and ferritin levels 
X 
 
 
 
 
 
 
 
Review eligibility criteria 
X 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
Iron studies with or without baseline 
complete metabolic panel (depending on 
history of liver or kidney disease) 
X 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
Assign study number 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical and obstetric history review 
X 
 
 
 
 
 
 
 
Initiate Oral iron study medications 
 
 
X 
 
 
 
 
 
Schedule a visit at the CTRU for IV Iron 
infusion or coordinate with Antepartum 
Unit 
 
X 
 
 
 
 
 
 
IV iron infusion appointment, 1st session 
 
X 
 
 
 
 
 
 
Second IV iron infusion, as needed based 
on initial hemoglobin levels 
 
X 
 
 
 
 
 
 
Monitoring during the IV Iron infusion 
and post-infusion period 
 
X 
 
 
 
 
 
 
Blood draw to check CBC at 4 weeks after 
initiation of oral iron/ post-completion of 
IV infusions 
 
 
 
X 
 
 
 
 
Blood draw to check CBC 8 weeks after 
initiation of oral iron/ post-completion 
of IV infusions 
 
 
 
 
X 
 
 
 
Blood draw to check CBC during the time 
of admission for delivery (SOC) 
 
 
 
 
 
X 
 
 
Blood draw to check hemoglobin, 
hematocrit level post-delivery (SOC) 
 
 
 
 
 
 
X 
(per OB) 
SAE/ AE monitoring, reporting, recording 
 
X 
X 
X 
X 
X 
X 
X 
Pregnancy/ prenatal data collection 
 
 
 
 
 
X 
 
 
Delivery data collection 
 
 
 
 
 
X 
X 
 
Neonatal data collection 
 
 
 
 
 
X 
X 
 


 
 
 
 
• Prominently display participant status in the patient’s EHR for all providers to see  
• Include information regarding the management plan that corresponds to the study group  
• Provide the patient with brochure that outlines the study group and management 
algorithm  
• Include contact information to allow study staff to be reached as needed for questions.  
 
 
7.6 Post Randomization Participant Management 
 
 Clinical management 
• A summary of the research management algorithm for patients in each of the two study 
groups will be strategically posted at clinic locations and will be placed in each 
participant’s medical record; the patient should have an informational copy of their labs 
and management algorithm and advised to bring to scheduled and unscheduled visits.  
• OB Welch Clinical labs staff will be available to draw labs at 4 and 8 weeks after 
initiation of therapy: if a patient has Clinical labs that are indicated for any other reason 
by primary OB, the study labs can be paired with the clinical draw. 
• IV iron group will receive additional follow up for adverse symptoms 1 week post 
infusion and 4 and 8 weeks after initiation of treatment 
• Oral iron group will receive survey of symptoms 1, 4, and 8 weeks after initiation of 
treatment  
• Routine pregnancy care at each center will be given to patients by clinical providers 
trained in the study protocol.  
• Ultrasound for anatomy or fluid/growth and antenatal testing will be per clinical center’s 
routine.  
 
7.7 Participant follow up  
 
A clinic visit (preferred method) or follow up call will occur at 6 (4-12 weeks) weeks after 
delivery in accordance with routine postpartum care.  Several data forms will be used during this 
follow-up process using forms for maternal outcomes, newborn outcomes, NICU outcomes, and 
6 weeks follow up forms. These forms, HIPAA compliant, will be entered into the REDCap 
database.  
 
At randomization, 24-28 weeks (up to 30 complete weeks if necessary) 4 and 8 weeks post- 
initiation (Oral iron)/ post-treatment (IV iron) labs will be collected as described above. We will 
also perform chart abstraction to determine hemoglobin levels at the time of admission for 
delivery and 1 day postpartum (these labs are drawn routinely at LPCH).  
 
In addition to routine prenatal and postpartum clinic visits, participants will be followed up to 
ascertain maternal and infant status related to re/admissions and ER or unscheduled visits. The 
records of any ER visits or hospitalizations will be obtained for review. 
 
 
 
 


 
 
 
 
 
 
7.8 Study Drug, Dispensing 
 
Stanford’s investigational pharmacy will dispense IV iron infusion to CTRU. CTRU will 
dispense/administer study infusion(s) to research participant and will provide oral acetaminophen 
prior to the initiation of IV iron infusion.   
 
Participants receive medication supplies from the outpatient pharmacy. Oral iron tablets will be 
distributed 100 tablets at a time. Medication dispensing may occur in the intervening periods 
between visits in case of emergency, loss, or schedule changes. A tracking mechanism is 
maintained for all dispensing actions. 
 
The participant will report by monitoring survey how many doses were missed. The only reasons 
that a patient may return the bottle include expired medication or if she does not tolerate the 
medication and is switched to something else. If the participant doesn’t have enough left to 
supply her until her next visit, she will be dispensed a new bottle and told to complete the current 
supply and then start the new bottle 
 
7.9 Biospecimens  
 
7.9.1 Maternal Blood Samples will be collected at the following time points (see table below): 
• Randomization (at 24-28 weeks age gestational age-optimal) may collect up to 32 weeks  
• 4 weeks after post –initiation for oral group or post-completion for intravenous group. 
• 8 weeks after treatment post –initiation for oral group or post-completion for intravenous 
group. 
• Delivery*  
• Postpartum day 1* 
 
* collected with routine delivery at LPCH. Routine CBC at birth admission and postpartum day 1 
with LPCH. This will be in the patient’s electronic health record. 
 
8. DELIVERY (including pregnancy loss after randomization) AND POST-DELIVERY 
 
Outcome Data Collection and Chart Review Delivery Outcomes will be ascertained - on an 
ongoing basis until discharge.  
Study personnel will abstract the hospital charts and compete information for REDCap entry: 
- 
Labor and Delivery Data 
- 
Neonatal Outcome Data 
- 
Placental Pathology (review only if sent by primary Obstetrician) 
- 
NICU admission form (if indicated)  
- 
Adverse Event  
- 
Study Intervention Discontinuation and Participation 
discontinuation/withdrawal  
 
 


 
 
 
 
9.  PROCEDURES FOR INACTIVE/ LOST/ REFUSED PARTICIPANTS AND MISSED 
VISITS  
 
9.1 Overview  
 
Staff will use a systematic approach in attempting to recover reluctant participants, i.e., those 
who have either expressed interest in dropping out of the study or appear to be likely to drop-out 
due to noncompliance with any aspect of the study. 
 
The goals to avoid drop-out and accomplish drop-out recovery include the following:  
1. to ensure that participants are not pushed to the point that they refuse to participate further 
2. to continue to engage participants through some form of contact (e.g., phone, e-mail) and 
allow an opportunity to determine participants’ concerns and problem-solve for solutions to 
concerns and barriers to participation,  
3. to foster some form of continued participation (e.g., even an agreement to allow future 
contact)  
 
The general approach to drop-out recovery will involve contact by the study coordinator in an 
attempt to:  
1. identify barriers to participation  
2. problem-solve for solutions to overcome identified barriers  
3. apply motivational enhancement methods 
 
In situations where a participant’s behavior suggests that she does not wish to participate, the 
participant can be removed from the study.  
 
9.2 Definition of Participant Status. 
 
 For purposes of the study, we define the following terms related to trial participation status: 
 
 • Active status – active if iron medication therapy is managed according to the study algorithm. 
There may be instances where a provider is managing the participant’s medications in 
accordance with the study protocol (i.e. many may commonly prescribe oral iron for anemia 
without iron studies), but the participant is obtaining medications from a (non-study) pharmacy 
of his/her choosing; in such situations, the participant is considered to be active as well.  
 
• Inactive status –inactive or non-compliant if her iron medication is no longer being managed 
according to the study protocol with CTRU and she has not withdrawn consent for regular 
measurement (follow-up) visits or event monitoring is still being performed.  
 
• Lost status –lost-to-follow-up if she has missed several appointments and cannot be contacted 
by any ordinary means (e.g., home phone, cell phone, mail, email, fax, etc.), clinic staff does not 
know the participant’s whereabouts, and alternative contacts either do not know where the 
participant is or cannot be contacted themselves.  
 


 
 
 
 
· Withdrawn/Refused status –participant is considered to be withdrawn if he/she has withdrawn 
consent to participate in the study and refuses further contact for any reason. 
 
 
10. ADVERSE EVENT REPORTING 
 
Serious adverse events that meet any of the following criteria: 
• fatal or life-threatening 
• result in significant or persistent disability, 
• require or prolong hospitalization, 
• result in a congenital anomaly/birth defect, or 
• are important medical events that investigators judge to represent significant hazards or harm to 
research participants.  
 
Specifically, any AE that meets any of these criteria (maternal death, ICU admission stroke, 
myocardial infarction, cardiomyopathy, fetal death or neonatal death) will be documented and 
reported as a SAE.  
In addition, any unexpected event/ unanticipated problems which the investigator identifies will 
be reported.  
10.1 Data Safety Monitoring Board  
A DSMB will be activated to ensure the safety of participants by analyzing data and to 
oversee the validity and integrity of the data.  
Any serious adverse event or unanticipated problem will be reported to the Stanford IRB. A Data 
Safety Monitoring Board (DSMB) will be established, with responsibility to monitor all aspects 
of the study and monitor data and oversee participant safety. DSMB participants include the 
senior faculty, staff, and representatives from the Stanford Maternal Fetal Medicine Division, 
Internal Medicine, Hematology and Nephrology. The DSMB will meet once a year to monitor 
safety, to advise on study progress and performance, protocol modification, or whether there 
should be early termination. 
The outcome of reviews will be relayed to the IRB and protocol director.  
10.2 Reporting of Adverse Events  
In addition, the following maternal events are examples of adverse events to be reported: 
Maternal or perinatal allergic reaction:  
• Angioedema, anaphylaxis or generalized skin rash  
• Transfer to Chronic Care facility (neonatal)  


 
 
 
 
• Maternal arrhythmia (especially QT prolongation) or congestive cardiac failure 
(EF<45%) 
• Neonatal arrhythmia (especially QT prolongation)  
• Any adverse event leading to discontinuation of study medication or suspected to be due 
to the medication  
• Maternal pulmonary thromboembolism  
• Maternal admission to ICU  
• Neonatal IVH Grade III or IV  
• Prolonged maternal or term neonatal hospitalized 
 
11.  QUALITY CONTROL  
Quality control and assurance are the responsibility of every member of the IDA trial. 
 
All clinic personnel are responsible for understanding the protocol procedures.  
 
Research Staff responsibilities: 
 
• Maintaining the integrity of the protocol and regulatory document binder. 
• 
Developing a data entry system that incorporates real-time data quality assurance 
features, such as range and logic checks  
• Monitoring site initiation requirements.  
• Monitoring the screening and randomization processes to ensure randomization of 
eligible participants and appropriate randomization allocation of participants.  
• Generating timely web-based reports describing clinic and study performance, including 
but not limited to: a) recruitment b) visit adherence and visit completeness c) study 
intervention) data entry e) data completeness f) outcomes documentation 
• Monitoring documentation of 100% of potential outcomes  
 
 
12.  STATISTICAL ANALYSIS 
  
12.1 Statistical Considerations  
 
Efficacy Endpoint(s): The primary outcome for this study is to assess the delta in hemoglobin pre 
and post intervention in both treatment groups. Our hypothesis is that the rate of increase of 
intravenous iron will be approximately 1.5g/dL higher in the IV iron cohort versus the oral iron 
cohort 
Secondary Efficacy Endpoint(s): The secondary outcomes for this study include the following:  
- 
correction of anemia at the time of birth hospitalization,  
- 
rates of blood transfusion,  


 
 
 
 
- 
neonatal outcomes such as APGARs and NICU admissions 
- 
maternal/neonatal infection  
- 
mode of delivery (NTSV)  
- 
infant birth weight  
 
12.2 Sample size determination  
 
We estimated minimum sample size required for 90% power, one-sided α=0.025, and estimated 
effect sizes for the outcomes of change in proportion of women (Hg <11g/dL) by birth 
hospitalization based on the findings of previous studies26,47. Based on these parameters and 
allowing for 20% drop-out rate, the study requires 32 subjects per arm. The analysis plan and 
sample size calculation were developed in consultation with Maternal-Fetal Medicine Senior 
Biostatistician, Stephanie Leonard, PhD (Co-I). We plan to recruit up to 80 patients to account 
for potential loss to follow up. We plan to update this sample size calculation based on a pilot 
study that we are conducting at our institution. We also plan for a much larger sample size in 
order to conduct analyses stratified by race/ethnicity and to study rare secondary clinical 
outcomes, as well as possibly compare formulations of intravenous iron, none of which has been 
done previously.  
 
12.3 Analyses  
 
We will conduct an intent-to-treat analysis to compare the primary and secondary outcomes 
between the treatment arms. The primary outcome is the mean change in hemoglobin in oral vs 
IV iron over 4 weeks as well mean change in hemoglobin pre delivery. The primary outcome 
will be assessed using t-tests. Baseline characteristics between the groups will be compared using 
t-tests and chi-square tests. If there is an imbalance between the treatment arms, we will use 
multivariable regression modeling. Differences will be considered statistically significant at 
P<0.05. 
 
 
13. POTENTIAL CONTINGENCY PLANS  
 
Patient compliance will be assessed in this trial by pill count in the oral arm and by keeping a 
log of the study infusions in the IV arm. If enrollment is low, we will engage additional obstetric 
providers whose patients deliver at LPCH such as San Mateo clinic. The IRB revision with the 
updated formulation ferumoxytol is approved. The goal remains to identify the optimal intravenous 
iron preparation that combines lowest risk optimal amount of elemental iron with least burden on 
the patient (fewest visits, short infusion times) with optimal amount of elemental iron.   
 
 
References  
1.  
Shim J-Y, Kim MY, Kim YJ, et al. Efficacy and safety of ferric carboxymaltose versus 
ferrous sulfate for iron deficiency anemia during pregnancy: subgroup analysis of Korean 
women. doi:10.1186/s12884-018-1817-y 
2.  
Breymann C, Milman N, Pharma V, et al. Patient Blood Management and Life Cycle 


 
 
 
 
Management Open Access Ferric carboxymaltose vs. oral iron in the treatment of 
pregnant women with iron deficiency anemia: an international, open-label, randomized 
controlled trial (FER-ASAP). J Perinat Med. 2017;45(4):443-453. doi:10.1515/jpm-2016-
0050 
3.  
Govindappagari S, Burwick RM. Treatment of Iron Deficiency Anemia in Pregnancy with 
Intravenous versus Oral Iron: Systematic Review and Meta-Analysis. Am J Perinatol. 
2019;36(4):366-376. doi:10.1055/s-0038-1668555 
4.  
Lewkowitz AK, Gupta A, Simon L, et al. Intravenous compared with oral iron for the 
treatment of iron-deficiency anemia in pregnancy: a systematic review and meta-analysis. 
J Perinatol. 2019;39(4):519-532. doi:10.1038/s41372-019-0320-2 
5.  
Wolf M, Chertow GM, Macdougall IC, Kaper R, Krop J, Strauss W. C L I N I C A L M E 
D I C I N E Randomized trial of intravenous iron-induced hypophosphatemia. 2018. 
doi:10.1172/jci.insight.124486 
6.  
Beckert RH, Baer RJ, Anderson JG, Jelliffe-Pawlowski LL, Rogers EE. Maternal anemia 
and pregnancy outcomes: a population-based study. J Perinatol. 2019;39(7):911-919. 
doi:10.1038/s41372-019-0375-0 
7.  
Pavord S, Daru J, Prasannan N, Robinson S, Stanworth S, Girling J. UK guidelines on the 
management of iron deficiency in pregnancy. Br J Haematol. October 2019:bjh.16221. 
doi:10.1111/bjh.16221 
8.  
Lops VR, Hunter LP, Dixon LR. Anemia in pregnancy. Am Fam Physician. 
1995;51(5):1189-1197. http://www.ncbi.nlm.nih.gov/pubmed/7709894. Accessed 
February 1, 2020. 
9.  
ACOG Practice Bulletin No. 95: Anemia in Pregnancy. Obstet Gynecol. 2008;112(1):201-
207. doi:10.1097/AOG.0b013e3181809c0d 
10.  
Mei Z, Cogswell ME, Looker AC, et al. Assessment of iron status in US pregnant women 
from the national health and nutrition examination survey (NHANES), 1999-2006. Am J 
Clin Nutr. 2011;93(6):1312-1320. doi:10.3945/ajcn.110.007195 
11.  
Leonard SA, Main EK, Scott KA, Profit J, Carmichael SL. Racial and ethnic disparities in 
severe maternal morbidity prevalence and trends. Ann Epidemiol. 2019. 
doi:10.1016/j.annepidem.2019.02.007 
12.  
Bothwell TH. Iron requirements in pregnancy and strategies to meet them. In: American 
Journal of Clinical Nutrition. Vol 72. ; 2000. doi:10.1093/ajcn/72.1.257s 
13.  
Talbot L, Maclennan K. Physiology of Pregnancy. 
14.  
Recommendations to prevent and control iron deficiency in the United States. Centers for 
Disease Control and Prevention. MMWR Recomm Rep. 1998;47(RR-3):1-29. 
15.  
Cantor AG, Bougatsos C, Dana T, Blazina I, McDonagh M. Routine iron supplementation 
and screening for iron deficiency anemia in pregnancy: A systematic review for the U.S. 
preventive services task force. Ann Intern Med. 2015;162(8):566-576. doi:10.7326/M14-
2932 
16.  
Reveiz L, Gyte GM, Cuervo LG, Casasbuenas A. Treatments for iron-deficiency anaemia 
in pregnancy. Cochrane Database Syst Rev. October 2011. 
doi:10.1002/14651858.CD003094.pub3 
17.  
Tolkien Z, Stecher L, Mander AP, Pereira DIA, Powell JJ. Ferrous Sulfate 
Supplementation Causes Significant Gastrointestinal Side-Effects in Adults: A Systematic 
Review and Meta-Analysis. Strnad P, ed. PLoS One. 2015;10(2):e0117383. 
doi:10.1371/journal.pone.0117383 


 
 
 
 
18.  
Kriplani A, Mahey R, Dash BB, Kulshrestha V, Agarwal N, Bhatla N. Intravenous iron 
sucrose therapy for treatment of anaemia in pregnancy. J Obstet Gynaecol (Lahore). 
2011;31(July):34. doi:10.1016/S0020-7292(12)61706-8 
19.  
Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmén J. Update on adverse drug events 
associated with parenteral iron. Nephrol Dial Transplant. 2006;21(2):378-382. 
doi:10.1093/ndt/gfi253 
20.  
Pharmaceuticals A. FERAHEME- ferumoxytol injection HIGHLIGHT S OF 
PRESCRIBING INFORMAT ION FULL PRESCRIBING INFORMATION : 
CONTENTS * WARNING : RISK FOR SERIOUS HYPERSENSITIVITY / 
ANAPHYLAXIS REACTIONS 1 INDICATIONS AND USAGE 2 DOSAGE AND 
ADMINISTRATION 3 DOSAGE FORMS AND ST. 
21.  
U.S. FDA 2008. 
http://www.accessdata.fda.gov/drugsatfdadocs/nda/2009/022180s000PharmR.pdf. 
22.  
U.S. National Library of Medicine. 
23.  
Grzeskowiak LE, Qassim A, Jeffries B, Grivell RM. Approaches for optimising 
intravenous iron dosing in pregnancy: a retrospective cohort study. Intern Med J. 
2017;47(7):747-753. doi:10.1111/imj.13467 
24.  
Wang C, Graham DJ, Kane RC, et al. Comparative risk of anaphylactic reactions 
associated with intravenous iron products. JAMA - J Am Med Assoc. 2015;314(19):2062-
2068. doi:10.1001/jama.2015.15572 
25.  
Breymann C, Auerbach M. Iron deficiency in gynecology and obstetrics: Clinical 
implications and management. Hematology. 2017;2017(1):152-159. 
doi:10.1182/asheducation-2017.1.152 
26.  
Auerbach M, Adamson JW. How we diagnose and treat iron deficiency anemia. Am J 
Hematol. 2016;91(1):31-38. doi:10.1002/ajh.24201 
27.  
Wolf M, Chertow GM, Macdougall IC, Kaper R, Krop J, Strauss W. C L I N I C A L M E 
D I C I N E Randomized trial of intravenous iron-induced hypophosphatemia. 2018. 
doi:10.1172/jci.insight.124486 
28.  
Khalafallah A, Dennis A, Bates J, et al. A prospective randomized, controlled trial of 
intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy. J Intern 
Med. 2010. doi:10.1111/j.1365-2796.2010.02251.x 
29.  
Peña-Rosas JP, De-Regil LM, Dowswell T, Viteri FE. Daily oral iron supplementation 
during pregnancy. In: Peña-Rosas JP, ed. Cochrane Database of Systematic Reviews. 
Chichester, UK: John Wiley & Sons, Ltd; 2012. doi:10.1002/14651858.CD004736.pub4 
30.  
Qassim A, Gergis RG, Jeffries B, Grivell RM, Grzeskowiak LE. Use of intravenous iron 
polymaltose in the management of iron deficiency in pregnancy: A retrospective cohort 
study. Aust New Zeal J Obstet Gynaecol. 2018. doi:10.1111/ajo.12645 
31. 
Moretti D, Goede JS, Zeder C, Jiskra M, Chatzinakou V, Tjalsma H, Melse-Boonstra A, 
Brittenham G, Swinkels DW, Zimmermann MB. Oral iron supplements increase hepcidin 
and decrease iron absorption from daily or twice-daily doses in iron-depleted young 
women. Blood. 2015. doi: 10.1182/blood-2015-05-642223 
32. 
Stoffel, Siebenthal, Moretti, Zimmerman. Oral iron supplementation in iron-deficient 
women: how much and how often? Molecular Aspects of Medicine. 75 (2020)  

ICF_000.pdf: 
Comparison of Oral Ferrous Sulfate to Intravenous Ferumoxytol in 
Antepartum Iron Deficiency Anemia 
Informed Consent Form 
NCT04253626 
November 28, 2023 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 1 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
 
Are you participating in any other research studies? _____ Yes _____No 
 
SUMMARY 
 
Your consent to participate is being sought for research purposes and your  
participation is entirely voluntary. The purpose of the research is to determine 
the extent to which the treatment of antepartum iron deficiency anemia in the 
third trimester with intravenous iron increases hemoglobin by birth compared to 
oral iron supplementation. The duration of your participation is expected to be 
around 12 weeks long. The study procedures will include randomizing you to 
either receive oral iron medications or intravenous iron infusions. There is a 50% 
chance for you to be assigned to either treatment arm. You will be expected to 
complete a follow-up blood draw 4 weeks and 8 weeks after initiation of 
whichever study treatment you are randomized to to re-check your iron levels. 
You will also be asked to complete four short surveys during your participation. 
Both treatments are standard treatments used for medical care and FDA 
approved but there are always unforeseeable risks when participating in any 
research study that will be discussed in greater detail further along in this 
consent form. Potential benefits of participation include improved hemoglobin 
levels at the time of delivery, less risk for blood transfusion, and less risk of 
adverse maternal and neonatal outcomes often associated with anemia in 
pregnancy. The alternative to participating in this study would be to continue 
planned medical care during your pregnancy. 
 
PURPOSE OF RESEARCH 
 
You are invited to participate in a research study of iron deficiency anemia 
treatments during pregnancy.  We hope to determine the extent to which the 
treatment of antepartum iron deficiency anemia in the third trimester with 
intravenous iron increases hemoglobin by birth compared to oral iron 
supplementation. Intravenous iron (ferumoxytol) and oral iron (ferrous sulfate) 
are both FDA-approved and will be used according to labeling. You were selected 
as a possible participant in this study because you are pregnant and have been 
diagnosed with iron-deficiency anemia. 
 
Anemia in pregnancy is a risk factor for increased rates of maternal and perinatal 
morbidity, and iron deficiency represents over 70% of the anemias diagnosed in 
pregnancy. Iron deficiency anemia (IDA) presents one treatable and potentially 
reversible cause of severe maternal morbidity. However, guidelines do not exist 
for treatment of IDA in late pregnancy and the current standard– oral iron 
supplementation – is known to have adverse side effects and a slow rate of effect. 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 2 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
 
The study aims to add key research in this area to improve the management of 
antepartum anemia, particularly for women that are at risk for poor outcomes with 
later presentations of anemia in pregnancy. 
 
If you decide to terminate your participation in this study, you should notify Dr. 
Deirdre Lyell at 650-725-5720.   
 
This research study is looking for 80 participants with iron deficiency anemia in 
pregnancy, and the study will be done in Stanford University.   
 
VOLUNTARY PARTICIPATION  
 
Your participation in this study is entirely voluntary.  Your decision not to 
participate will not have any negative effect on you or your medical care.  You 
can decide to participate now but withdraw your consent later and stop being in 
the study without any loss of benefits or medical care to which you are entitled. 
 
DURATION OF STUDY INVOLVEMENT  
 
This research study is expected to take approximately 2 years, with 12- 16 
weeks of active participation by each participant. Medical record review will be 
done for you and your baby. 
 
PROCEDURES 
 
If you choose to participate, the Protocol Director Dr. Deirdre Lyell and her 
research study staff will randomize you to either receive oral iron medications or 
intravenous iron infusions. There is a 50% chance for you to be assigned to 
either treatment arm. 
 
A blood draw (about 2 teaspoons) for iron studies may be performed prior to 
initiation of any intervention to confirm eligibility if not already performed as part 
of standard clinical care.  A complete metabolic panel and/or complete blood 
count may also be performed.  
 
If you are randomized to the intravenous iron infusion arm, you will: 
• You will receive an intravenous injection of ferumoxytol 510 mg to be 
started between 28-35 weeks gestation. The iron infusions take about 15-
30 minutes and you will be monitored for another 15-30 minutes post-
infusion to observe for any adverse reactions. Your vital signs will also be 
closely monitored during and post-infusion. 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 3 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
• If your hemoglobin level is between 7-8.9 g/dL, you will be given 2 doses 
of the iron infusions 3-8 days apart 
• If your hemoglobin level is between 9- 10.9 g/dL, you will be given a single 
dose of the iron infusion 
• Prior to each infusion of IV iron, you will receive a 650mg dose of oral 
tylenol (acetaminophen) approximately 20 minutes before beginning the 
infusion 
• Have a blood draw of about 1 teaspoon each at 4 and 8 weeks after 
completion of the iron infusion/s to check for your complete blood counts 
 
If you are randomized to the oral iron medication arm, you will: 
• Start taking iron (ferrous sulfate) tablets by mouth every other day after 
randomization up to the day of delivery 
• If your hemoglobin level is between 7-8.9 g/dL, you will need to take 2 
tablets of iron 325 mg tablets every other day until you deliver 
• If your hemoglobin level is between 9- 10.9 g/dL, you will need to take 1 
tablet of iron 325 mg tablet every other day until you deliver 
• Have a blood draw of about 1 teaspoon each at 4 weeks and 8 weeks after 
you start taking the oral iron medication to check for your complete blood 
count (CBC) 
 
You will be asked to complete four short surveys total about your symptoms: one 
at the time of enrollment and at 1, 4, and 8-12 weeks after initiating therapy. 
The survey is 21 questions in length and should take no more than 5 minutes to 
complete. 
 
Your and your baby’s medical records will be reviewed. 
 
This research will not include whole genome sequencing. 
 
Your blood samples collected for the study will not be saved for future research. 
Your information and/or specimens will not be used or distributed for future 
research studies even if all identifying information is removed. 
 
Any of your specimens which are used in research may result in new products, 
tests or discoveries. In some instances, these may have potential commercial 
value and may be developed and owned by the Investigators, Stanford University 
and/or others.  However, donors of specimens do not retain any property rights 
to the materials.  Therefore, you would not share in any financial benefits from 
these products, tests or discoveries. 
 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 4 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
Future Use of Private Information and/or Specimens: 
 
Research using private information and/or specimens is an important way to try 
to understand human disease.  You are being given this information because the 
investigators want to save private information and/or specimens for future 
research.   
 
Identifiers might be removed from identifiable private information and/or 
identifiable specimens and, after such removal, the information and/or 
specimens could be used for future research studies or distributed to another 
investigator for future research studies without additional informed consent from 
you. 
 
PARTICIPANT RESPONSIBILITIES           
 
As a participant, your responsibilities include:  
• Follow the instructions of the Protocol Director and study staff. 
• Take the study drug as instructed.  
• Keep your study appointments.  If it is necessary to miss an appointment, 
please contact the Protocol Director or research study staff to reschedule 
as soon as you know you will miss the appointment. 
• Tell the Protocol Director or research study staff about any side effects, 
doctor visits, or hospitalizations that you may have. 
• Keep the study drug in a safe place, away from children and for your use 
only. 
• Ask questions as you think of them. 
• Tell the Protocol Director or research staff if you change your mind about 
staying in the study. 
 
WITHDRAWAL FROM STUDY 
 
If you first agree to participate and then you change your mind, you are free to 
withdraw your consent and discontinue your participation at any time.  Your 
decision will not affect your ability to receive medical care for your disease and 
you will not lose any benefits to which you would otherwise be entitled.  
 
If you decide to withdraw your consent to participate in this study, you should 
notify Dr. Deirdre Lyell at 650-725-5720. 
 
If you withdraw from the study, or the study medication is stopped for any 
reason: 
• Your iron deficiency anemia may persist 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 5 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
The Protocol Director may also withdraw you from the study and the study 
medication may be stopped, without your consent for one or more of the 
following reasons:   
 
o Failure to follow the instructions of the Protocol Director and study staff. 
o The Protocol Director decides that continuing your participation could be 
harmful to you. 
o You need treatment not allowed in the study. 
o The study is cancelled.  
o Other administrative reasons. 
o Unanticipated circumstances. 
 
POSSIBLE RISKS, DISCOMFORTS, AND INCONVENIENCES  
 
There are risks, discomforts, and inconveniences associated with any research 
study.  These deserve careful thought.  You should talk with the Protocol 
Director if you have any questions. 
 
• Venipuncture will be performed multiple times during the study and risks of 
venipuncture include mild discomfort for a short period of time, bruising, 
and in rare cases infection. 
• Oral ferrous sulfate is commonly used during pregnancy and postpartum 
for treatment of iron deficiency anemia. Adverse reactions of oral ferrous 
sulfate include gastrointestinal effects such as darkening of stools, 
abdominal pain, heartburn, nausea (7.5%), vomiting (5.0%), and 
constipation. 
• Ferumoxytol is an FDA approved formulation of intravenous iron for 
treatment of iron deficiency. Intravenous iron is routinely used to treat 
pregnant women with severe iron deficiency anemia. The following adverse 
reactions of ferumoxytol iron have been reported: nausea (3.1%), 
dizziness (2.6%), hypotension (2.5%), peripheral edema, headache, 
vomiting, abdominal pain, chest pain, itching, fever, back pain/muscle 
spasms and rash, including permanent skin discoloration due to IV 
extravasation.  
• Serious hypersensitivity reactions, including anaphylaxis, which can be life 
threatening and fatal have been reported to occur in Ferumoxytol. 
Anaphylaxis has been reported to occur for approximately 34 persons per 
100,000. Symptoms associated with an allergic reaction such as wheezing, 
shortness of breath have been reported in 3.7% of the cases.  For this 
reason, we exclude patients with a history of two or more medication 
allergies. In addition, we infuse the medication slowly over 30 minutes, 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 6 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
and you will be monitored for at least 30 minutes afterwards. Ferumoxytol 
can also transiently affect the diagnostic capability of MRI for 3 months 
after infusion.  
• If you are randomized to the intravenous iron infusion arm, you will need 
to come in for a separate appointment/s to do the infusion/s and will need 
to allot some time for the procedure 
• It is possible that this study may involve unforeseeable risks to the 
participant or her fetus, including death.  
• Adverse reactions of oral acetaminophen include gastrointestinal 
symptoms, loss of appetite, itching, rash, headache, dark urine, clay-
colored stools, or jaundice, and rarely, serious allergic reactions.  
 
POTENTIAL BENEFITS                              
 
Potential benefits include improved hemoglobin levels at the time of delivery, less 
risk for blood transfusion, and less risk of adverse maternal and neonatal 
outcomes often associated with anemia in pregnancy. 
 
We cannot and do not guarantee or promise that you will receive any benefits 
from this study. 
 
ALTERNATIVES 
 
There are no alternative treatment approaches or procedures other than to 
choose not to participate in the study. If you choose not to participate, your 
clinical provider will determine with you the appropriate treatment as based on 
clinical guidelines. 
 
PARTICIPANT’S RIGHTS 
 
You should not feel obligated to agree to participate.  Your questions should be 
answered clearly and to your satisfaction.  If you decide not to participate, tell 
the Protocol Director.   
 
You will be told of any important new information that is learned during the 
course of this research study, which might affect your condition or your 
willingness to continue participation in this study. 
 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 7 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
ClinicalTrials.gov 
 
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov, as required by U.S. Law.  This Web site will not 
include information that can identify you.  At most, the Web site will include a 
summary of the results.  You can search this Web site at any time. 
 
CONFIDENTIALITY 
 
This research is covered by a Certificate of Confidentiality from the National 
Institutes of Health. The researchers with this Certificate may not disclose or use 
information, documents, or biospecimens that may identify you in any federal, 
state, or local civil, criminal, administrative, legislative, or other action, suit, or 
proceeding, or be used as evidence, for example, if there is a court subpoena, 
unless you have consented for this use. Information, documents, or 
biospecimens protected by this Certificate cannot be disclosed to anyone else 
who is not connected with the research except, if there is a federal, state, or 
local law that requires disclosure (such as to report child abuse or communicable 
diseases but not for federal, state, or local civil, criminal, administrative, 
legislative, or other proceedings, see below); if you have consented to the 
disclosure, including for your medical treatment; or if it is used for other scientific 
research, as allowed by federal regulations protecting research subjects. 
 
The results of this research study may be presented at scientific or medical 
meetings or published in scientific journals.  Your identity and/or your personal 
health information will not be disclosed except as authorized by you or as 
required by law.  However, there is always some risk that even de-identified 
information might be re-identified.  
 
Patient information may be provided to Federal and other regulatory agencies as 
required.  The Food and Drug Administration (FDA), for example, may inspect 
research records and learn your identity if this study falls within its jurisdiction. 
 
 
 
 
 
 
 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 8 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
Authorization To Use Your Health Information 
For Research Purposes 
 
Because information about you and your baby’s health is personal 
and private, it generally cannot be used in this research study 
without your written authorization.  If you sign this form, it will 
provide that authorization.  The form is intended to inform you about 
how your and your baby’s health information will be used or 
disclosed in the study.  Your and your baby’s information will only be 
used in accordance with this authorization form and the informed 
consent form and as required or allowed by law.  Please read it 
carefully before signing it.   
 
What is the purpose of this research study and how will my 
health information be utilized in the study? 
The study would like to determine the extent to which the treatment 
of antepartum iron deficiency anemia in the third trimester with 
intravenous iron increases hemoglobin by birth compared to oral iron 
supplementation.  
 
You and your baby’s health information will be used to contextualize 
the results we get from the study samples and the assigned study 
intervention. The health information we collect for use in a 
publication for this study will be coded. 
 
Your information relating to this study, including your name, medical 
record number, and date of birth may be shared with the billing 
offices so that claims may be appropriately submitted to the study 
sponsor or to your insurance company for clinical services and 
procedures provided to you during the course of this study. 
 
Do I have to sign this authorization form? 
You do not have to sign this authorization form.  But if you do not, 
you will not be able to participate in this research study including 
receiving any research-related treatment.  Signing the form is not a 
condition for receiving any medical care outside the study. 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 9 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
If I sign, can I revoke it or withdraw from the research later? 
If you decide to participate, you are free to withdraw your 
authorization regarding the use and disclosure of your health 
information (and to discontinue any other participation in the study) 
at any time.  After any revocation, your health information will no 
longer be used or disclosed in the study, except to the extent that 
the law allows us to continue using your information (e.g., necessary 
to maintain integrity of research).  If you wish to revoke your 
authorization for the research use or disclosure of your health 
information in this study, you must write to:  
Dr. Deirdre Lyell 
453 Quarry Road 
Palo Alto, CA, 94304 
 
What Personal Information Will Be Obtained, Used or 
Disclosed? 
Your and your baby’s health information related to this study, may be 
used or disclosed in connection with this research study, including, 
but not limited to, you and your child's name, medical record 
numbers, phone numbers, address, electronic mail address, and 
dates of birth. We will also collect obstetrical and neonatal outcome 
data, including dates of service. We will collect you and your child's 
clinical data including demographics, medical history, maternal 
prenatal/ obstetric history, ultrasound imaging/radiology data, 
laboratory test results, diagnosis codes, prescriptions or medications, 
pregnancy complications, labor and delivery data, clinical narratives, 
maternal post-partum outcomes, treatment regimens, neonatal data 
including outcomes and complications. 
 
Who May Use or Disclose the Information? 
The following parties are authorized to use and/or disclose your 
health information in connection with this research study: 
• The Protocol Director Dr. Deirdre Lyell 
• The Stanford University Administrative Panel on Human 
Subjects in Medical Research and any other unit of Stanford 
University as necessary 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 10 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
• Research Staff 
 
Who May Receive or Use the Information? 
The parties listed in the preceding paragraph may disclose your 
health information to the following persons and organizations for 
their use in connection with this research study:  
• The Office for Human Research Protections in the U.S. 
Department of Health and Human Services 
• Other collaborators as approved by the IRB 
• Maternal and Child Health Research Institute  
• The Food and Drug Administration 
• The National Institutes for Health 
 
Your information may be re-disclosed by the recipients described 
above, if they are not required by law to protect the privacy of the 
information. 
 
When will my authorization expire? 
Your authorization for the use and/or disclosure of your health 
information will end on December 31, 2050 or when the research 
project ends, whichever is earlier.  
 
Will access to my medical record be limited during the study? 
To maintain the integrity of this research study, you may not have 
access to any health information developed as part of this study until 
it is completed.  At that point, you would have access to such health 
information if it was used to make a medical or billing decision about 
you (e.g., if included in your official medical record).  
 
 
________________________________             
  ______________ 
Signature of Adult Participant                                        Date 
 
 
________________________________             
 
Print Name of Adult Participant        


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 11 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
FINANCIAL CONSIDERATIONS 
 
Payment/Reimbursement 
 
You will not be paid to participate in this research study. 
 
 
Costs 
 
If you participate in this study, the study will pay for those services, supplies, 
procedures, and care associated with the study that are not a part of your 
routine medical care.  However, there may be additional costs to you.  These 
include basic expenses like transportation and the personal time it will take to 
come to the study visits.  You and/or your health insurance must pay for 
services, supplies, procedures, and care that are required during this study for 
routine medical care.  You will also be responsible for any co-payments 
and/or deductibles as required by your insurance.  Participation in this 
study is not a substitute for health insurance.   
 
Sponsor 
 
The National Institutes for Health is providing financial support and/or material 
for this study.  
  
COMPENSATION for Research-Related Injury 
 
All forms of medical diagnosis and treatment – whether routine or experimental 
– involve some risk of injury.  In spite of all precautions, you might develop 
medical complications from participating in this study.  If such complications 
arise, the Protocol Director and the research study staff will assist you in 
obtaining appropriate medical treatment.  In the event that you have an injury or 
illness that is directly caused by your participation in this study, reimbursement 
for all related costs of care first will be sought from your insurer, managed care 
plan, or other benefits program.  You will be responsible for any associated 
co-payments or deductibles as required by your insurance. 
 
If costs of care related to such an injury are not covered by your insurer, 
managed care plan or other benefits program, you may be responsible for these 
costs.  If you are unable to pay for such costs, the Protocol Director will assist 
you in applying for supplemental benefits and explain how to apply for patient 
financial assistance from the hospital. 
 
You do not waive any liability rights for personal injury by signing this form. 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 12 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
CONTACT INFORMATION  
 
Questions, Concerns, or Complaints:  If you have any questions, concerns or 
complaints about this research study, its procedures, risks and benefits, or 
alternative courses of treatment, you should ask the Protocol Director, Dr. 
Deirdre Lyell at 650-725-5720.  You should also contact her at any time if you 
feel you have been hurt by being a part of this study.  
 
Independent Contact:  If you are not satisfied with how this study is being 
conducted, or if you have any concerns, complaints, or general questions about 
the research or your rights as a participant, please contact the Stanford 
Institutional Review Board (IRB) to speak to someone independent of the 
research team at (650)-723-5244 or toll free at 1-866-680-2906.  You can also 
write to the Stanford IRB, Stanford University, 1705 El Camino Real, Palo Alto, 
CA 94306. 
 
Appointment Contact: If you need to change your appointment, please contact 
Maternal Fetal Medicine Research at 650-725-5720. 
 
EXPERIMENTAL SUBJECT’S BILL OF RIGHTS 
 
As a research participant you have the following rights.  These rights include but 
are not limited to the participant's right to: 
• 
be informed of the nature and purpose of the experiment;  
• 
be given an explanation of the procedures to be followed in the medical 
experiment, and any drug or device to be utilized;  
• 
be given a description of any attendant discomforts and risks reasonably 
to be expected;  
• 
be given an explanation of any benefits to the subject reasonably to be 
expected, if applicable;  
• 
be given a disclosure of any appropriate alternatives, drugs or devices 
that might be advantageous to the subject, their relative risks and 
benefits; 
• 
be informed of the avenues of medical treatment, if any available to the 
subject after the experiment if complications should arise;  
• 
be given an opportunity to ask questions concerning the experiment or 
the procedures involved;  
• 
be instructed that consent to participate in the medical experiment may 
be withdrawn at any time and the subject may discontinue participation 
without prejudice;  
• 
be given a copy of the signed and dated consent form; and  


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 13 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
• 
be given the opportunity to decide to consent or not to consent to a 
medical experiment without the intervention of any element of force, 
fraud, deceit, duress, coercion or undue influence on the subject's 
decision. 
 
Signing your name means you agree to be in this study and that you will receive 
a copy of this signed and dated consent form.  
 
 
 
_____________________________________                ____________ 
Signature of Adult Participant 
 
 
 
   
   Date 
 
 
_____________________________________             
Print Name of Adult Participant                                         
 
 
The IRB determined that the permission of one parent is sufficient for research in 
accordance with 21 CFR 50.55. 
 
 
_____________________________________                ____________  
Signature of Person Obtaining Consent  
 
   
  Date 
 
 
_____________________________________             
Print Name of Person Obtaining Consent 
 
 
 
The following witness line is to be signed only if the consent is provided as a summary 
form and accompanied by a short form foreign language consent. 
 
 
 
_____________________________________                     ____________ 
Signature of Witness                                                              Date 
 
_____________________________________            
 
Print Name of Witness                                         
 
(e.g., staff, translator/interpreter, family member) 
 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Dr. Deirdre Lyell 
IRB# 54788 
Protocol Title:   Pilot Trial for Prevention of Anemia at Time of Birth Admission 
 
Page 14 of 14 
 
SU_MainICF_HIPAA rev 120219 
IRB Use Only 
Approval Date:  November 28, 2023 
Expiration Date: November 23, 2024 
Participant ID: 
• Translated short form must be signed and dated by both the participant (or their 
LAR) AND the witness. 
• The English consent form (referred to as the "Summary Form" in the regulations): 
− Must be signed by the witness AND the Person Obtaining Consent (POC). 
− The non-English speaking participant/LAR does not sign the English consent. 
− The non-English speaking participant/LAR should not sign the HIPAA participant line 
− If the participant or the LAR is non-English speaking, the Person Obtaining Consent 
(POC) must ensure that 1) the LAR's Description of Authority is completed and 2) 
that any questions or options presented by the consent form are documented and 
initialed by the POC on the Summary Form, per the participant's wishes, as they are 
understood during the consent process.