Global Network for Women's and Children's Health Research Maternal Newborn Health Registry
Conditions: Pregnancy Outcome Trends in Low-resource Geographic Areas
Sponsor: NICHD Global Network for Women's and Children's Health

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COVID-19 prevalence during pregnancy and pregnancy outcomes in 8 low and 
middle-income sites: A Global Network Study 
 
Protocol 
 
Robert L. Goldenberg1, Sarah Saleem2, Masum Billah3, Patricia L Hibberd4, Nancy F Krebs5 
Tracy Nolen6, and Elizabeth M. McClure6 on behalf of the Global Network for Women’s and 
Children’s Health Research investigators*  
1Columbia University, New York, NY  
2Aga Khan University, Karachi, Pakistan 
3ICDDR,B, Dhaka, Bangladesh 
4Boston University, Boston, MA 
5University of Colorado at Denver, Denver, CO  
6RTI International, Durham, NC 
 
 
 
 
 
 
Version 1.2 
July 1, 2020 
August 1, 2020 
August 30, 2021 

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Contents 
Abstract.......................................................................................................................................................................... 3 
Global Network Study Investigators.............................................................................................................................. 4 
Abbreviations ................................................................................................................................................................ 6 
Statement of the problem ............................................................................................................................................... 7 
1.1 Introduction ......................................................................................................................................................... 7 
1.2 Study objectives ................................................................................................................................................... 7 
1.3 Study aims ........................................................................................................................................................... 7 
1.4 Rationale .............................................................................................................................................................. 8 
1.5 Prior COVID-19 research .................................................................................................................................... 9 
Method and Procedures ................................................................................................................................................. 9 
2.1 Study design ........................................................................................................................................................ 9 
2.2 Study population ................................................................................................................................................ 10 
2.3 Study intervention .............................................................................................................................................. 10 
2.4 Primary and secondary outcomes ...................................................................................................................... 11 
Statistical considerations ............................................................................................................................................. 11 
3.2 Available population .......................................................................................................................................... 13 
3.3 Estimate of projected recruitment time .............................................................................................................. 13 
3.4 Risks and benefits .............................................................................................................................................. 13 
3.5 Ethical considerations ........................................................................................................................................ 13 
Data management and quality control ......................................................................................................................... 14 
Appendix 1. Study collection form: Signs and symptoms ........................................................................................... 16 
Appendix 2. Study collection form: Knowledge, attitudes and practices .................................................................... 17 
Appendix 3. Sample Study Consent Form ................................................................................................................... 18 
Appendix 4. Budgetary assumptions ........................................................................................................................... 21 
Appendix 5.  Protocol Version Control ....................................................................................................................... 22 
REFERENCES .......................................................................................................................................................... 23 
 
 
 

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Abstract 
Background 
There is limited information regarding coronavirus infections that occur during pregnancy, 
especially in low and middle-income countries (LMIC). To date, there are many unanswered 
questions related to COVID-19 infection in pregnant women especially from LMICs. This is due 
to many factors, including the few reported cases; the lack of sufficient testing to understand the 
extent of the infection in the population as a whole; the impact of asymptomatic infection on the 
pregnancy and its outcome; women don't have access to authentic knowledge and that COVID-
19 is epidemiologically distinct from SARS and MERS, making extrapolation difficult. 
Methods 
 
In 8 LMIC sites, we will determine the prevalence of COVID-19 infection during pregnancy using 
antibody testing at or near to delivery and determine the association between COVID-19 
exposure during pregnancy and maternal, fetal and neonatal outcomes. Additionally, we aim to 
explore knowledge, attitudes and prevention practices regarding COVID-19 during pregnancy. 
 
Over a 24-month period, approximately 170 women per month from each site will be asked to 
complete a questionnaire and provide a blood sample at or near delivery, which will be tested 
for COVID-19 antibodies; quality control will be provided by RTI. Through the data that are 
routinely collected by the Global Network’s Maternal Newborn Health Registry (MNHR), we will 
evaluate fetal, neonatal, and maternal outcomes.  
 
The Global Network’s COVID-19 study will be an important contribution to the understanding of 
the prevalence of COVID-19 among pregnant women as well as the association between 
COVID-19 and pregnancy outcomes in LMICs. 
 
 

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Global Network Study Investigators 
Site Investigators 
 
Site 02 (Democratic Republic of Congo) 
Carl Bose, M.D. 
Principal Investigator 
University of North Carolina School of Medicine 
Chapel Hill, North Carolina 
cbose@med.unc.edu  
 
Antoinette Tshefu, MD, PhD, MPH  
Senior Foreign Investigator 
Kinshasa School of Public Health 
antotshe@yahoo.com 
 
Site 03 (Zambia) 
Wally Carlo, MD 
Principal Investigator 
University of Alabama at Birmingham 
Birmingham, Alabama 
Wcarlo@PEDS.UAB.EDU 
 
Elwyn Chomba, MBChB, DCH, MRCP 
Senior Foreign Investigator 
University Teaching Hospital 
Lusaka, Zambia 
echomba@zamnet.zm 
 
 
Site 06 (Guatemala) 
Nancy Krebs, MD 
Principal Investigator 
University of Colorado School of Medicine 
Denver, Colorado 
Nancy.krebs@cuanschutz.edu 
 
Manolo Mazariegos, MD 
Investigator 
INCAP 
Guatemala City, Guatemala 
mmazariegos@incap.int  
 
Site 07 (Bangladesh) 
William Petri, MD 
Principal Investigator 
University of Virginia 
Charlottesville, Virginia 
wap3g@virginia.edu 
 
Rashidul Haque, MD 
Senior Foreign Investigator 
ICDDR,B 
Dhaka, Bangladesh 
rhaque@icddrb.org 
 
Site 08 (Belagavi, India) 
 
Richard Derman, MD, MPH 
Principal Investigator 
Thomas Jefferson University 
Philadelphia, PA 
Richard.Derman@jefferson.edu 
 
 
Shivaprasad S. Goudar MD, MHPE 
Senior Foreign Investigator 
KLE Academy of Higher Education and Research 
Belgaum, India 
sgoudar@jnmc.edu 
 
Site 09 (Pakistan) 
Robert L. Goldenberg, MD 
Principal Investigator 
Columbia University 
New York, New York 
rlg88@columbia.edu 
 
Sarah Saleem, MD 
Senior Foreign Investigator 
Aga Khan University 
Karachi, Pakistan 
sarah.saleem@aku.edu 
 
Site 11 (Nagpur, India) 
Patricia L. Hibberd, MD, PhD 
Principal Investigator 
Boston University 
Boston, Massachusetts  
 plh0@bu.edu  
 
Archana Patel, MD, DNB, MSCE, PhD 
Senior Foreign Investigator 
Lata Medical Research Foundation 
Nagpur, India 
Dr_apatel@yahoo.com 
 
 

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Site 12 (Kenya) 
Ed Liechty, MD 
Principal Investigator 
Indiana University School of Medicine 
Indianapolis, Indiana 
eliecht@iupui.edu 
 
Fabian Esamai, MBChB, MMed, MPH, PhD 
Senior Foreign Investigator 
Moi University School of Medicine 
Eldoret, Kenya 
fesamai2007@gmail.com 
National Institute of Child Health and Human Development (NICHD) 
Marion Koso-Thomas, MD, MPH 
Medical Officer, Global Network for Women’s and Children’s Health  
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 
kosomari@mail.nih.gov 
 
RTI International 
Elizabeth M. McClure, PhD 
Principal Investigator, Data Coordinating Center 
RTI International, Durham, NC 
mcclure@rti.org 
 
Tracy Nolen, DrPh 
Senior Statistician, Data Coordinating Center 
tnolen@rti.org 
 
Nalini Peres-da-Silva, BS 
Potocol Manager, Data Coordinating Center 
nperesdasilva@rti.org 

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Abbreviations 
 
 
ANC: Antenatal Care 
CI: Confidence Intervals 
DCC: Data Coordinating Center 
DMC: Data Monitoring Committee 
DMS: Data Management System 
DRC: Democratic Republic of Congo 
GN: Global Network for Women’s and Children’s Health Research 
LMIC: Low/middle income countries 
MNHR: Maternal Newborn Health Registry 
NICHD: Eunice Kennedy Shriver National Institute of Child Health and Human Development 
QA: Quality assurance 
RR: Relative risks 
WHO: World Health Organization 
 
 

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Statement of the problem 
 
1.1 Introduction 
 
The first reports of a pneumonia of unknown cause surfaced from Wuhan, China in late 
December of 2019. After cases multiplied and reached most countries, the World Health 
Organization declared COVID-19, a novel coronavirus, a public health emergency of 
international concern on January 30, 2020.  As of March, cases were found in every country of 
the world. To date, more than nine million cases and nearly 500,000 deaths have occurred. The 
WHO maintains the risk assessment of COVID-19 at “very high”5. While high-income countries 
have been among those most affected at the start of the pandemic, concern prevails about how 
low- and middle-income countries (LMICs), with fragile health systems and poverty will face the 
pandemic6,7. Very few data are available about the prevalence of COVID-19 infection in many 
LMICs, and especially regarding the prevalence of COVID-19 infection among pregnant women 
in these settings. 
 
There are also limited data regarding the impact of coronavirus infections on pregnancy, 
especially in LMICs. Results from one study of SARS-CoV in 20 pregnant women suggested 
that SARS appears to be associated with a higher risk of serious adverse outcomes compared 
with risks observed with COVID-19 to date. One-third of pregnant women with SARS-CoV 
required mechanical respiration and the case fatality rate was 15%. In one published report of 
MERS, another coronavirus, on 11 pregnant women, there was a case fatality rate of 27%. 
There was little or no evidence of maternal to fetal transmission with either virus.  Although 
there are limited reports, COVID-19 seems to be associated with fewer serious adverse 
pregnancy outcomes compared to SARS and MERS1. However, a review performed in the 
United Kingdom found that premature delivery was found in almost half of women hospitalized 
with COVID-191. Reports assessing the vertical transmission of COVID-19 have shown mixed 
results2,3,4.   
 
To date, given the few reported confirmed cases, the lack of sufficient testing to understand the 
extent of the infection in the population, and the unknown impact of both symptomatic and 
asymptomatic infection on the pregnancy outcomes, there are many unanswered questions 
related to COVID-19 infection in pregnant women especially from LMICs where access to 
authentic information is limited. Because COVID-19 is epidemiologically distinct from SARS and 
MERS, extrapolation is difficult from the experience of prior coronavirus outbreaks.  
 
1.2 Study objectives 
To determine the prevalence of COVID-19 antibodies in pregnant /recently delivered women in 
8 Global Network sites (in DRC, Kenya, Zambia, Bangladesh, India [2 sites], Pakistan and 
Guatemala) and its association with pregnancy outcomes. 
 
1.3 Study aims 
 
• 
To determine the prevalence of COVID-19 antibodies in recently delivered 
women in 8 Global Network sites using antibody testing. 

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• 
To compare the maternal, fetal, and neonatal outcomes of COVID-19 antibody 
positive women vs. antibody negative women including low-birthweight, preterm 
birth, fetal growth restriction, stillbirth, and neonatal mortality. 
• 
To assess knowledge, attitudes and practices of pregnant women related to 
COVID-19 and its prevention during pregnancy. 
 
1.4 Rationale 
 
The risk of spontaneous abortion, stillbirth, neonatal mortality, and preterm birth are important 
questions to address in pregnant women infected with the COVID-19 virus, as are the rates and 
types of congenital infections and malformations, and fetal growth restriction. This is especially 
true among the fetuses and newborns of infected mothers in LMICs. Each of these outcomes is 
likely associated with the gestational age at which the mother develops the infection.  
 
To understand the overall scope of the COVID-19 pandemic, we believe that using a screening 
antibody at delivery or in the post-partum period will be the most efficient way to obtain this 
information. If this test is performed in a population of women at delivery, over time, we will be 
able to assess the extent of the COVID-19 pandemic in these locations and the trends in the 
proportion of the pregnant population infected with COVID-19. Also, with evidence of COVID-19 
positive antibodies at the end of pregnancy, we will assess the clinical history during pregnancy 
to help determine if there was evidence of an acute respiratory infection, when it occurred, and 
its severity. In addition, we will be able to compare those pregnancies with evidence of COVID-
19 positive antibodies to those with negative antibodies to answer a number of questions related 
to associated outcomes such as mean birthweight and low-birthweight, mean gestational age 
and preterm birth, fetal growth restriction, and other outcomes such as stillbirth, neonatal 
mortality, and congenital anomalies. The antibody testing will be used as a surrogate for COVID 
-19 infection. 
 
Another component of this study will be to determine mothers’ knowledge, attitude and practices 
related to COVID-19 in pregnancy. Knowledge will be assessed by questions related to 
methods of prevention, symptoms, transmission, and methods of detection and sources of care 
for COVID-19 or place to contact with disease symptoms. Attitudes toward the disease will 
include questions related to willingness or unwillingness to receive testing, or care. Concerns 
related to fear of social exclusion, being under lockdown/home isolation will be explored since 
anecdotes suggest people often hide symptoms or do not test because of these issues. We will 
also explore issues related to women’s practice related to COVID-19 such as if fears will cause 
women to not attend prenatal care or deliver at health facilities. We will explore the use of 
protective measures such as using a mask, social isolation, etc. These issues will be explored 
during a prenatal care visit or by telephone if that appears to be the better option. 
 
The Global Network sites are uniquely poised to answer these and other important questions 
related to COVID-19 during pregnancy in a number of low-resource settings. Since 2008, the 
Global Network has enrolled and completed follow-up of approximately 60,000 pregnancies 
each year across 8 sites in Africa, Asia and Latin America, focusing on outcomes such as 
preterm birth, fetal growth restriction, and maternal, fetal and newborn mortality.  
 

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1.5 Prior COVID-19 research 
 
The SARS-COV-2, the virus which causes COVID-19, is highly contagious, with a Ro between 2 
and 3.58,9 (Ro denotes the average number of secondary cases of an infectious disease that 
one case would generate in a completely susceptible population).  An important issue related to 
prevalence is that a significant proportion of infections have been found to be asymptomatic. 
Initial studies performed in China reported up to 80%8 of infections to be very mild or 
asymptomatic. A large review of children who had contact with infected persons in China found 
15% of infected children to be completely asymptomatic10. Among quarantined passengers and 
crew on a cruise ship who were infected with SAR-COV-2, 17.9% were asymptomatic. Based 
on a study performed in Santa Monica, California that detected antibodies, researchers 
estimated that up to 4% of the general population could have already been infected. Because 
asymptomatic cases can actively excrete the virus, they pose a challenge to infection control as 
well as to understanding disease outcomes on a population basis.  
 
Studies of different populations have repeatedly found that the groups at highest risk of 
unfavorable outcomes include people over 65, more likely to be male and with preexisting 
medical conditions such as hypertension, diabetes, cardiovascular disease or chronic lung 
disease11,12. There is limited information about the impact of COVID-19 on infants and children, 
but troubling data have emerged recently on a late onset inflammatory disease associated with 
COVID-19 infection in children. 
 
There are two types of tests that are either currently available or will soon be available to 
confirm that a person has an active COVID-19 infection or has had a COVID-19 infection in the 
past. The first type is a direct test, such as PCR, that actually determines if the virus is present. 
This can be performed on nearly any fluid or tissue collected. Currently, many PCR tests 
targeting the viral genome are used to determine the presence or absence of COVID-19 on 
nasal or oropharyngeal swabs, but these tests can only be used to determine which people (or 
which tissues) are presently infected. Once the disease is cleared and the subject recovers, the 
test can no longer confirm that COVID-19 was present or was the cause of the illness. The 
second type of test is an indirect IgG antibody test that is likely to turn positive at about 10 days 
into the course of a COVID-19 infection. These tests likely will remain positive long after the 
infection is over, but the duration of a positive antibody test after the infection has cleared has 
not been determined. There are recent reports of people with a previous history of COVID-19 
infection who are antibody positive who appear to acquire the disease again or remain infected. 
IgM tests have been used to indicate recent or active infection among neonates, but their value 
is unclear. Thus, the direct viral test (PCR) is useful for documenting an active infection, while 
the antibody test documents a history of infection but provides no information about when the 
infection occurred. IgG antibody tests are less useful in documenting active infection.  
 
Method and Procedures 
 
2.1 Study design 
This will be a prospective, population-based, cohort study conducted within the Global 
Network’s Maternal and Newborn Health Registry (MNHR)13, a population-based observational 
study which enrolls approximately 60,000 pregnant women per year across 8 Global Network 
sites.   

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2.2 Study population  
For screening purposes, all women in the MNHR will be eligible to be screened for the COVID-
19 study at time of enrollment into the MNHR.  This study will follow the same inclusion and 
exclusion criteria as the MNH Registry (MNHR) to screen: 
 
Inclusion criteria: 
• 
Pregnant women intending to deliver within study cluster 
Exclusion Criteria: 
• 
Decline to provide consent to include data in the study 
 
While it seems preferable for sites to focus on women who plan to deliver at a health facility, 
sites will be able to recruit cluster women who plan to deliver at home or elsewhere provided 
arrangements are established to draw blood to test for COVID-19 antibodies at or following 
delivery. Similarly, the site may elect to routinely collect the maternal blood samples away from 
the delivery location, as long as procedures are in place to ensure the samples are collected 
and maintained appropriately. 
 
2.3 Study intervention 
 
Trained MNHR study staff will perform the following additional procedures with consenting 
MNHR study participants as follows: 
 
Each woman will be asked to provide a blood specimen of approximately 3-5 cc at or near 
delivery (at delivery or 14 days after) to be tested for COVID-19 antibodies. The person 
collecting the specimen will be a trained member of the registry staff. The study will use one 
standardized testing protocol across all sites. Due to the rapid advancements in testing 
protocols, the final  testing protocol and specific antibody test will be determined closer to study 
launch, with the aim to use the best quality test that is feasible at the time the study is initiated. 
Tests will be run at each site as soon as the logistics of testing allow. We expect each site to be 
able to perform their own analyses using a standardized assay kit, with central quality support 
provided by RTI International.  
 
One questionnaire (Appendix 1) will be administered around the time of delivery (as close as 
possible to delivery but within two weeks of delivery if at all possible) to determine significant 
events during the pregnancy with a focus on symptoms of COVID-19 infection including cough, 
shortness of breath or breathing difficulty, fever, chills/shaking, muscle pain, headache, sore 
throat, and loss of taste or smell, based on the WHO criteria.14 The questionnaire will also 
address the timing of the occurrence of her symptoms. We will also ask about symptoms that 
may have occurred prior to the pregnancy but after January 2020 to capture potential COVID-19 
infections predating the pregnancy. 
 
Information related to any COVID-19 tests performed, other significant illnesses and 
hospitalizations, and contacts with others infected with COVID-19 will also be collected. We will 
also ask about COVID-19 related symptoms at the time the sample is collected. 
 

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A second questionnaire addressing knowledge, attitudes and practice related to COVID-19 
prevention, detection and treatment can be administered at any time during the pregnancy and 
can be administered to all women in the MNHR, even if they are not part of the antibody study 
(Appendix 2). The KAP questionnaire will continue to be collected as long as blood specimens 
are being collected and tested for COVID-19 antibodies.   
 
Using the MNHR case report forms, we will obtain information related to pregnancy outcome 
including stillbirth, preterm birth (<37 weeks gestation), birthweight (g), neonatal mortality 
(neonatal deaths <28 days), and fetal growth restriction. We will obtain infant’s hospital course 
and medical illnesses, hospitalizations as well as death until 28 days of age. Infants and 
mothers’ outcomes to 42 days post-delivery will be also obtained as we do for all MNHR 
enrollees.  
2.4 Primary and secondary outcomes 
• 
Prevalence of COVID-19 antibody positive results during pregnancy. 
• 
Fetal/neonatal outcomes: spontaneous abortion, stillbirth, birth weight (g), and 
fetal growth restriction, early (7-day) and late (28-day) neonatal death, cause of 
death, congenital infections, and malformations 
• 
Maternal outcomes: rate of infection, timing of infection, types of symptoms, 
death, cause of death 
• 
Knowledge, attitudes, and practices of pregnant women related to COVID-19 
infection during pregnancy 
Definitions for outcomes will be consistent with the MNHR protocol. 
Statistical considerations 
 
3.1 Sample size and data analyses plans 
 
Given the many unknowns about the COVID-19 pandemic in LMICs, estimating an appropriate 
sample size for different study outcome comparisons is difficult. The percent of women who will 
become infected during their pregnancy is unknown and there will likely be high variability 
across sites.  Thus, it is important to have a sufficient sample size to a) obtain a precise within 
site estimate of COVID-19 prevalence (i.e., antibody positivity), and b) estimate the association 
of maternal, fetal, and neonatal outcomes with COVID-19 infection status across sites.  
 
With respect to prevalence estimation, a sample size of 2,000 per site provides 0.84 probability 
of obtaining a 95% confidence interval with a half-width of 0.01 if the true underlying prevalence 
is 0.05. This same sample size also provides high probability (>0.99) of obtaining a 95% CI with 
half-width of 0.02 for a true underlying prevalence of 0.25 and with a half-width of 0.03 for a true 
underlying prevalence of 0.50. 
 
For assessing the association between maternal, fetal and neonatal outcomes with antibody 
status based on Global Network data, a number of outcomes of interest have a prevalence of 
about 3% in our sites (i.e., stillbirth, neonatal death, congenital anomalies).  
 

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The power to detect a relative risk (RR) of 1.5 for women with positive antibody results 
compared to those who were not based on a two-sided chi-square test with α=0.05 and 
assumed antibody positivity rates are portrayed in Figure 1 for a range of sample sizes. With 
2,000 participants per site at 8 sites resulting in a total sample size of 16,000 participants, there 
is 80% power to detect a RR of 1.5 if the underlying antibody positivity rate is at least 8%.  While 
we expect prevalence of COVID-19 to vary by site, an overall rate of 8% across all sites is 
assumed to be reasonable.  
 
 
Figure 1.  Statistical Power for an outcome with a baseline prevalence of 3% and a RR=1.50 at 
various levels of antibody positivity 
 
 
 
 
 
Thus, for the purpose of this study, testing women over the study period would allow us to 
determine COVID-19 prevalence trends over time. With the sample size target of 2,000 in each 
site, we will have sufficient power to estimate the impact of COVID-19 maternal infection on 
several important pregnancy outcomes. Each of the 8 sites will aim to recruit and conduct 
COVID-19 antibody testing for a minimum of 2,000 mothers (approximately 170 per month) for 
the study period.  While the initial study was planned for a one-year period, with the ongoing 
COVID-19 pandemic, the study will be extended until at least June 2022. With the extension, 
each site will continue to enroll approximately 170 women monthly at or immediately after 
delivery to reach a sample size of approximately 24,000.   
 
Because the sites will vary in terms of the number of potentially eligible pregnant women, RTI 
will work with each site to develop a sampling scheme that will reflect the population of pregnant 
women and distribute the recruitment evenly across the year. We are also aware that some 
sites may not be able to reach the goal of 170 recruited women per month. However, each site 
should aim to enroll as close to that target as possible for the duration of the study. We also 
realize that the extent and timing of the COVID-19 pandemic in each site is unknown and there 

13 
 
will be every effort made to accommodate this study to the situation at each site. For that 
reason, we will evaluate recruitment for each site monthly in order to make the appropriate 
adjustments and adjust the time frame of the study accordingly. 
 
At the time the initial batch of antibody testing is completed, if the prevalence of positive results 
is markedly low at any given site, it is unlikely meaningful information will be obtained with 
respect to antibody positivity and its association with maternal, fetal, neonatal outcomes. As 
such, the study subcommittee will have the ability to stop enrollment for a site if antibody testing 
is not yielding positive results.  Specifically, if no positive results have been identified in the first 
500 participants at a site, a review by the protocol committee will be triggered as the probability 
of the final prevalence exceeding 2% is <0.01%. 
 
The statistical analyses plan (SAP) includes details of analytic strategies that will be employed 
for this observational study. 
3.2 Available population 
 
It is our intent to conduct the COVID-19 study within the existing MNHR clusters in the GN sites.  
Currently, each site has approximately 3,000 – 6,000 pregnant women enrolled each year in the 
MNHR.  
 
3.3 Estimate of projected recruitment time 
 
The recruitment period will be 12-24 months at each site. Due to differences in the approval 
process, the start date may vary across the study sites. 
 
3.4 Risks and benefits 
 
This study does not pose significant risks to study participants. Minor risks could include 
discomfort while providing a blood sample or answering questions on the questionnaire. In 
addition, participants could feel distressed at learning the results of their tests (positive or 
negative previous SARS-COV-2 infection).   Finally, in some settings there may be stigma 
associated with positive COVID-19 infection.  To minimize the risk, all interviews about 
symptoms are confidential.  The antibody testing will be conducted as part of the research study 
and the participant may determine whether she wishes to know the results.   
 
3.5 Ethical considerations 
The knowledge, attitude and practice questionnaire will be incorporated into the routine MNHR 
questions and procedures. As such we will encourage completion at an early MNHR visit. 
However, we will be flexible about timing so that the questionnaire may be completed either 
during prenatal care or near delivery based on the convenience for the subject and staff. The 
date the questionnaire is completed will be collected so we will also be able to determine 
whether the time in the pregnancy the data is collected influences the results.  
 

14 
 
All women delivering within our sampling frame will be approached for consent for antibody 
sampling by trained MNHR staff.  Only women who provide informed consent (sample consent, 
Appendix 3) will be enrolled in the COVID-19 antibody protocol.  
 
All the Global Network sites will report data to the Global Network Data Coordinating Center 
(DCC), located at RTI International. The data will be used to evaluate protocol adherence and 
site performance (e.g., recruitment, loss to follow-up, data quality). The DCC will provide 
standardized progress reports to NICHD and the site investigators on a monthly basis to monitor 
outcome variables and adverse events. 
 
The Data Monitoring Committee (DMC) appointed by NICHD will oversee the conduct of this 
study at their bi-annual meetings. The DMC reports are made available to all participating 
institutions. 
 
 
Data management and quality control 
 
4.1 Data Management Overview 
As this study is being conducted as an addendum to the GN’s MNHR, COVID-19 study data will 
utilize the same DMS as the MNHR. The data will be collected in the local language 
electronically on forms programmed in Android Tablets in the RedCap Application. Personal 
identifying information will be recorded on MN00 (Screening Form) only. This information will be 
retained at the site only and will not be transmitted to the DCC. Data describing each mother 
and infant will be identified using a MNHR ID number only. Directly identifying information is not 
going to be entered into REDCap based EDC system.    
Precision and accuracy of actual data collected will be checked by chart review (random 5%) 
and internal procedures using the computer program.  Monthly audits and incomplete data 
reports will be performed by a review team).  Data editing and error resolution will be performed 
monthly.  Some of these activities may be shared with RTI. 
4.2  
Data Entry, Quality Checks and Transmission 
Data entry will be performed on Android tablets with the RedCap mobile application installed. 
Using RedCap, study staff will prospectively enter the data from study participants.  The 
RedCap DMS checks to make certain that entered values are acceptable, that all required fields 
are entered, and that items are consistent with other related items in the database. 
Validity checks will test for: 
• 
required fields 
• 
range checks 
• 
skip checks, and 
• 
consistency checks between multiple variables.  
All fields that are required to have a value will be checked to ensure they are not blank.  Skip 
logic has been programmed into RedCap as needed. 
All validity checks performed at data entry will be repeated on the database once it reaches RTI.  
Additional edit checks, such as across-form consistency checks will be performed as well. 
Detailed information about edit check failures will be sent back to the appropriate data collection 
site.  Data collection staff will be responsible for entering and updating/correcting all patient 

15 
 
records on the computer. Additional detail on the quality review and editing process is contained 
in the study Manual of Procedures (MOP). 
Transmission of Data to the Data Coordinating Center 
Data entered into offline REDCap mobile app should be uploaded to RTI REDCap server on a 
daily basis or as soon as there is a reliable WIFI connection. Strict confidentiality will be 
maintained for all data collected, and patient identifiers will not be available to RTI or the US PI.  
Security 
 
REDCap is a secure web application for building and managing online and offline data 
collection. REDCap software is 21 CFR Part 11, FISMA, and HIPAA-compliant. RTI 
International will assume responsibility for configuring RedCap database for Global Network 
institutions. All REDCap data are encrypted and password protected at all times (at rest and 
during transmission). Data can be collected either in an online web-based environment or by 
using the offline RedCap mobile application for sites without access to internet. The Android 
tablets will be stored in secure locations (i.e. lockboxes) which are only accessed by authorized 
study staff.  
4.3 Data Quality Reports 
After each data collection period (generally one month), the data center will produce a summary 
report including the following: 
• 
number of patients that were included in the study in that period 
• 
missing data rates 
• 
inconsistent data rates 
Additional data items may be included as determined by the MNHR investigators. 

16 
 
 
Appendix 1. Study collection form: Signs and symptoms 
 
 

17 
 
Appendix 2. Study collection form: Knowledge, attitudes and practices 
 
 

18 
 
Appendix 3. Sample Study Consent Form 
 
Global Network for Women’s & Children’s Health Research 
COVID-19 Study 
 
INVESTIGATORS:  
[LIST SITE INVESTIGATORS] 
 
 
SPONSOR: 
The Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD) 
 
You are being asked to participate in a research study related to COVID-19 for pregnant mothers. This 
study is funded by the U.S. National Institutes of Health. This form provides you with information about 
the study so that you can decide whether you would like to participate. A member of the research team 
will describe the study to you and answer all of your questions. Please read the information below and 
ask questions about anything you don’t understand before deciding whether or not to take part. You 
may also request that the research staff read the form to you.  
What is the purpose of the study? 
The purpose of this study is to learn about coronavirus (COVID-19) infection during pregnancy and if 
there are risks of the infection for the woman and her baby. 
Who will be in the study? 
A total of up to 30,000 women will be enrolled in this study from eight sites in sub-Saharan Africa, South 
Asia, and Latin America. In [insert site name], up to 8,000 women will be enrolled.  
You qualify for this study if you are a pregnant woman in the community.  
What will happen if I join this study? 
 
If you agree to participate, we will ask you some questions about your health and about your 
understanding of the coronavirus.   
While you are at the health facility to deliver your baby, the study team will also collect: 
• 
Information about your labor and delivery 
• 
Information about your baby, such as birthweight and health status at the time of delivery 
• 
A blood sample of 1 to 2 teaspoons full will be collected either in the facility at delivery, or 
afterward in a location convenient to you 
It will take no more than 30 minutes to complete the consent form, and answer questions for the study.  
After you are discharged from the health facility, a member of the study team will visit you at 6 weeks 
after delivery as part of the registry.  
To ensure that we have accurate and complete information about the health of you and your baby, we 
will access and collect information from the medical records at the health facilities where you and your 

19 
 
baby have received care. By agreeing to participate in this study, you are also agreeing to give 
permission for the study staff to access your medical records. We will take precautions to protect the 
information that is collected from your medical records. Only study staff will have access to this 
information. To further protect you and your baby, all of your information will be coded with a number 
in place of your name.  
The local research staff have been selected because of their skills, knowledge, and familiarity with your 
community. The research staff are here to support you during the study and should be contacted 
between visits if you have any questions or concerns. 
What are the risks and discomforts 
 
You may feel temporary discomfort when a blood sample is collected, but this will only last a few 
seconds. To minimize this, we will ensure research staff are well trained in the procedure.  
Another possible risk of participating in this study is that your name and personal information may be 
seen by persons who are not part of the project. To prevent this, you will be given an identification 
number that will be used in place of your name on all study documents.  
Information from this research study will be retained by [local institution] and RTI International in the 
United States (U.S.) and in the future may be included in a de-identified public use database managed by 
NICHD Data and Specimen Hub (DASH) in compliance with the U.S. National Institutes of Health (NIH) 
Public Access Policy. De-identified means that you and your baby will not be individually identified by 
name or other personal identifiers in the database. Your full name or any address details will not be 
included. Information released will not identify you or your baby’s participation in this research study.   
 
What are the benefits of participating? 
You will not receive any money from participating in this study, but your participation may provide 
important information that can be used in the future to prevent infection in mothers and babies. We will 
also provide the results of the blood sample test about whether you may or may not have been infected 
with COVID-19 at some time prior to the test. 
If new information about coronavirus in pregnancy becomes available during this study, this information 
will be given to you by [Insert name of Senior Investigator] or his/her staff.  
Will I have to pay for anything? 
It will not cost you anything to be in the study.  
Is my participation voluntary? 
Taking part in this study is voluntary. You have the right to refuse to participate or to withdraw your 
participation at any time. If you refuse or decide to withdraw, you will not lose any benefits or rights to 
which you are entitled. These actions will not have any negative effect on the health care you receive 
from your local health providers. You will still receive your normal medical care.  
Can I be removed from this study?  

20 
 
You will be withdrawn from the study if the research staff thinks that your participation may cause harm 
to you or your baby. The research staff may also remove you from the study for other reasons at their 
discretion. Also, the sponsor may stop the study at any time. 
What should you do if you have additional questions? 
If you have questions about this study or a project-related injury, you should contact [investigator 
contact]. If you have questions about your or your baby’s rights as a project participant, please contact 
[insert ethics committee contact]. 
If you have any questions about the study, please call [insert senior investigator]. 
Agreement to be in this study 
I have read this paper about the study or it was read to me. I understand the possible risks and benefits 
of this study. I know that being in this study is voluntary and I choose to be in this study. I understand I 
will get a copy of this consent form. 
Signature (or thumbprint): 
 
 
 
 
________ 
Date: 
 
______  
 
 
 
 
(Mother) 
 
Print Name: 
 
 
 
 
 
 
 
__ 
 
 
 
 
(Mother) 
 
Signature (or thumbprint): 
 
 
 
 
_________ 
Date: 
 
______  
 
 
 
 
(Parent/Guardian/Husband) 
 
Print Name: 
 
 
 
 
 
 
 
__ 
 
 
 
 
(Parent/Guardian/Husband) 
 
 
 

21 
 
Appendix 4. Budgetary assumptions  
 
Table 1 provides estimated costs per site* 
 
Table 1.  COVID-19 Supplement to the MNHR Estimated Site budgets 
 
Number 
 
 
Antibody test kits 
2,000  
$15.00 
$30,000.00 
Supplies to obtain blood samples (i.e., 
gloves, vials) 
2,000  
$2.00 
$4,000.00 
Copies of study forms 
2,000  
$1.00 
$2,000.00 
Personal protective equipment for MNH staff 
that will obtain samples 
2,000 
$2.50 
$5,000.00 
Lab staff to perform assays 
12 months  
$500.00 
$6,000.00 
Shipment of antibody test kits to sites  
 
$1,000.00 
TOTAL 
$48,000.00 
 
*Assumes that costs of data collection and data entry will be absorbed by the existing MNH 
registry staff 
 
 
Table 2.  COVID-19 Supplement Extension to the MNHR Estimated Site budgets  
 
Number 
 
 
Supplies to obtain blood samples (i.e., 
gloves, vials) 
1,000  
$2.00 
$2,000.00 
Personal protective equipment for MNH 
staff that will obtain samples 
1,000 
$2.50 
$2,500.00 
Lab staff to perform assays 
6 months  
$500.00 
$3,000.00 
TOTAL 
$7,500.00 
 
Appendix 5. COVID-19 Total Antibody ELISA Test  
• 
ZEUS ELISA SARS-CoV-2 IgG Test System test will be used for the study to retrospectively test for 
COVID-19 antibodies from blood samples 
• 
Determines if any the Immunoglobulin G (IgG) is present in a blood sample  
• 
Reports as a single “Positive” or “Negative” result which will be collected on MN25 COVID-19 Specimen 
Tracking log. 
• 
RTI will continue to work with Zeus Scientific and Global Network sites to import the ZEUS ELISA 
SARS-CoV-2 IgG test systems into the GN countries 
 
 

22 
 
Appendix 6.  Protocol Version Control 
Version 
 
Date 
Comments 
1.0 
 
7/1/2020 
Original version circulated for IRB/ERC review 
1.1 
 
8/1/2020 
Addition of data management section 
Table of contents and abbreviations 
1.2 
 
8/30/2021 
Increased sample size to 24,000  
Extended study period through June 2022 
 
 
 

23 
 
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