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Review Article • Rev. Latino-Am. Enfermagem 33 • 2025 • https://doi.org/10.1590/1518-8345.7517.4599 linkcopy

The inclusion of pregnant women in research during disease outbreaks globally: A scoping review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Objective: this scoping review aims to search the literature about conducting research on pregnant women during outbreaks globally and synthesize the findings to identify themes, analyze knowledge gaps, and provide evidence-based recommendations to inform future research.

Method: a comprehensive literature search was conducted in November 2023 using PubMed, Embase, CINAHL, Web of Science, Scopus, and Global Health databases. Key terms included “pregnancy,” “disease outbreaks,” “biomedical research,” and “eligibility criteria.” Twenty-three articles published between 2017 and 2023 were included in the synthesis.

Results: this review identified a pattern of exclusion of pregnant women from research during multiple disease outbreaks across diverse regions. The exclusion rates ranged from 52% to 97.8%. Ethical and moral concerns were raised, emphasizing the need for a shift toward the presumptive inclusion of pregnant women in research. Recommendations emerged from discussions on the risks and benefits of research participation, global institutional and strategic changes, and the standardized collection of pregnancy-specific data to inform public health responses.

Conclusion: this scoping review highlights the systemic exclusion of pregnant women from research during disease outbreaks, underscoring ethical concerns, critical knowledge gaps, and structural barriers while providing a foundation for advancing maternal health research during public health emergencies.

Descriptors:
Pregnant Women; Pregnancy; Disease Outbreaks; Biomedical Research; Clinical Studies as Topic; Eligibility Determination

Highlights:

(1) Pregnant women have been excluded from research during outbreaks globally. (2) Automatic ineligibility of pregnant women violates ethical principles. (3) Literature recommends a shift to the presumptive inclusion of pregnant women in research. (4) Surveillance systems collecting pregnancy-specific data should be strengthened.(5) Global institutional and strategic changes are needed to prioritize pregnant women.

Date of search	Search engine	Search terms	Retrieved citations
11/7/2023	PubMed	(((((“Pregnancy”[Mesh]) OR “Obstetrics”[Mesh]) OR “Pregnant Women”[Mesh] OR pregnan* [tiab] OR prenatal [tiab] OR antenatal [tiab] OR parturition [tiab] OR maternal [tiab] OR gestat* [tiab] OR perinatal [tiab] OR “pre-natal” [tiab] OR “ante natal” [tiab] OR “peri natal” [tiab] OR antepartum [tiab] OR “ante partum” [tiab]) AND ((“Communicable Diseases”[Mesh]) OR “Disease Outbreaks”[Mesh] OR “infectious disease” [tiab:~2] OR “infectious diseases” [tiab:~2] OR “disease outbreak” [tiab:~2] OR “disease outbreaks” [tiab:~2] OR epidemic* [tiab] OR pandemic* [tiab] OR outbreak* [tiab] OR pathogen* [tiab] OR plague* [tiab])) AND (“Clinical Protocols”[Mesh] OR “Clinical Studies as Topic”[Mesh] OR “Epidemiologic Studies”[Mesh] OR “Research Design”[Mesh] OR “Biomedical Research”[Mesh] OR “Data Collection”[Mesh] OR surveillance [tiab] OR “data collection” [tiab] OR trial* [tiab] OR random* [tiab])) AND (“Patient Selection”[Mesh] OR “Eligibility Determination”[Mesh] OR “Research Subjects”[Mesh] OR “patient selection” [tiab:~2] OR “research subject” [tiab:~2] OR “research subjects” [tiab:~2] OR eligibility [tiab] OR “research participant” [tiab:~2] OR “research participants” [tiab:~2])	340
11/8/2023	Embase	(‘pregnancy’/exp OR ‘pregnancy’ OR pregnant OR ‘prenatal’/exp OR prenatal OR antenatal OR perinatal OR ‘maternal’/exp OR maternal) AND (‘outbreaks’ OR ‘pandemics’/exp OR ‘pandemics’ OR ‘epidemics’/exp OR ‘epidemics’) AND (((‘clinical’/exp OR clinical) AND protocols OR ‘clinical’/exp OR clinical) AND (‘studies’/exp OR studies) OR ‘research’/exp OR research) AND (((‘patient’/exp OR patient) AND (‘selection’/exp OR selection) OR ‘research’/exp OR research) OR ‘surveillance’ AND subjects OR ‘eligibility criteria’/exp OR ‘eligibility criteria’)	180
11/8/2023	CINAHL	(‘pregnancy’/exp OR ‘pregnancy’ OR pregnant OR ‘prenatal’/exp OR prenatal OR antenatal OR perinatal OR ‘maternal’/exp OR maternal) AND (‘outbreaks’ OR ‘pandemics’/exp OR ‘pandemics’ OR ‘epidemics’/exp OR ‘epidemics’) AND (((‘clinical’/exp OR clinical) AND protocols OR ‘clinical’/exp OR clinical) AND (‘studies’/exp OR studies) OR ‘research’/exp OR research) OR ‘surveillance’ AND (((‘patient’/exp OR patient) AND (‘selection’/exp OR selection) OR ‘research’/exp OR research) AND subjects OR ‘eligibility criteria’/exp OR ‘eligibility criteria’)	121
11/10/2023	Web of Science	((pregnancy or pregnant or prenatal or antenatal or perinatal or maternal) AND (outbreaks or pandemics or epidemics) AND (clinical protocols or clinical studies or research or surveillance) AND (patient selection or research subjects or eligibility criteria))	374
11/10/2023	Scopus	((pregnancy or pregnant or prenatal or antenatal or perinatal or maternal) AND (outbreaks or pandemics or epidemics) AND (clinical protocols or clinical studies or research or surveillance) AND (patient selection or research subjects or eligibility criteria))	27
11/10/2023	Global Health	((pregnancy or pregnant or prenatal or antenatal or perinatal or maternal) and (outbreaks or pandemics or epidemics) and (clinical protocols or clinical studies or research or surveillance) and (patient selection or research subjects or eligibility criteria)).mp. [mp=abstract, title, original title, heading words, cabicodes words]	10
		Total	1,052

Article number	Author and date	Type of study	Sample, sample size, setting	Relevant findings	Observable measures	Limitations	Evidence level, quality
1	Al-Shimari, et al., 2023	Systematic review of observational studies	-44 reports published between 2011 and 2022 of hepatitis E outbreaks in 19 countries -Outbreak(s): Hepatitis E globally (2011-2022)	-4 of 44 outbreak reports included pregnancy screening as a method for outbreak detection -68% of the reports noted the number of confirmed cases among pregnant women -91% of the reports did not mention if the vaccine was given to pregnant women to prevent further transmission or future outbreaks	-Characteristics reported in outbreak studies -Interventions to prevent, detect, and contain outbreaks	-Authors noted limited and missing data, as well as gaps in public reporting processes	Level III, Quality B
2	Alirol, et al., 2017	Observational	-WHO-ERC* reviewed 24 protocols and 22 amendments for research studies on Ebola from Aug 2014 to April 2016 -Outbreak(s): Ebola in West Africa (2014-2016)	-Principles of justice and equitable access must be considered -WHO-ERC* requested that protocol amendments include pregnant women unless exclusion was justified by data demonstrating that the risk of treatment was likely to exceed potential benefits. -A global consultation was recommended on the criteria for including pregnant women in interventional studies for high-risk conditions to inform new regulations and guidelines	-Ethical reviews of observational studies and interventional protocols, including vaccinations	-Authors noted protocol inconsistencies, missing information, complex informed consents, as well as the time pressure inherent to accelerated reviews	Level III, Quality B
3	Costantine, et al., 2020	Observational	Online registry search of the international clinical trials database (www.clinicaltrials.gov) using the search term “COVID”, yielding 588 studies -Outbreak(s): COVID-19 global pandemic (2020)	-Only four studies (less than 1%) were specifically designed for pregnant women -More than two-thirds of the interventional studies specifically listed pregnancy as an exclusion criterion. -Missed opportunities to collect pregnancy-specific safety and efficacy data	-Studies specifically designed for pregnant women -Interventional studies -Studies with pregnancy as exclusion/inclusion criteria	-Study limited to trials available in a single registry	Level III, Quality B
4	Edwards & Kochhar, 2020	Expert opinion	-Ethics of conducting clinical research in an outbreak setting -Outbreak(s): Ebola in West Africa (2014-2016); Ebola in the DRC ^† (2018-2020)	-Pregnant women were excluded from vaccine trials and denied the Ebola vaccine in West Africa due to insufficient evidence of vaccine safety -Early community engagement, careful articulation of study design and risks and benefits of participation, and post-trial access to the intervention for participating populations, if deemed safe and effective, are recommended. -Impact of these recommendations on the DRC ^† Ebola outbreak in 2020	-Ethical considerations, core requirements, and recommendations for enhancing clinical trials during outbreaks	-Potential for author bias	Level V, Quality B
5	Einav, et al., 2020	Observational	Online registry search of the international clinical trials database (www.clinicaltrials.gov) using the search terms “COVID,” or “coronavirus,” or “SARS-CoV-2” up to April 2020, yielding 371 interventional studies -Outbreak(s): COVID-19 global pandemic (2020)	-68% of studies listed pregnancy as an exclusion criterion -76% of trials testing drugs excluded pregnant subjects -31% avoid mention of pregnancy at all in inclusion or exclusion criteria -Several trials investigating drugs with known safety profiles in pregnancy, interventions already used in pregnancy, or low-risk non-pharmacological interventions excluded pregnant women -Lack of differentiation of risk between stages of pregnancy -The assumed unwillingness of pregnant women to participate was a commonly cited reason for exclusion	-Interventional studies with pregnancy as an exclusion/inclusion criterion	-Study limited to trials available in single registry	Level III, Quality B
6	Ethics Working Group on ZIKV Research and Pregnancy, 2017	Consensus panel	-Working group of 15 interdisciplinary experts; consultations with over 60 experts -Outbreak(s): Zika in the Americas (2016)	-Prioritize the development of vaccines acceptable for use in pregnancy during outbreaks -Timely collection of data about vaccine safety and efficacy during pregnancy -Pregnant women should have fair access to vaccine trials with potential for benefit	-Guidance for Zika vaccine research among pregnant women -3 imperatives and 15 recommendations	-Potential for author bias	Level IV, Quality B
7	Farrell, et al., 2020	Expert opinion	-Ethical frameworks for inclusion in clinical trials -Outbreak(s): COVID-19 global pandemic (2020)	-Significant research gaps exist in COVID-19 surveillance among pregnant women -Pregnant women were excluded from drug trials, including hydroxychloroquine, remdesivir, and antiretrovirals -Recommends presumptive inclusion of pregnant women, not requiring consent from any other person, and prioritizing preclinical data needed for inclusion in future trials	-Outlines ethical frameworks and recommended strategies for inclusion in research	-Potential for author bias	Level V, Quality B
8	Frey, et al., 2019	Expert opinion	-Description of ongoing surveillance efforts to monitor Zika virus infections during pregnancy in the U.S. -Outbreak(s): Zika in the Americas (2016)	-Documentation and timely reporting of pregnancy status as part of laboratory testing and case reporting, link this with infant outcomes data - A surveillance system allows for more rapid response to the next public health emergency	-Existing surveillance systems -Strategies for future improvement	-Potential for author bias	Level V, Quality B
9	Goldfarb, et al., 2018	Qualitative	-Pregnant and recently postpartum women attending prenatal care at a large U.S. hospital completed surveys ( n =128) -Outbreak(s): Zika (hypothetical)	-77% accepted participation in at least one trial, more likely to accept if inactivated virus -Main motivators for participation included existing evidence of safety (59%), the desire to protect oneself (65%) and one’s baby (98%), perceptions of vaccine safety, and provider recommendations.	-Willingness of participants to enroll in a hypothetical vaccine trial -Attitudes and motivations for participation in vaccine research	-Relatively homogeneous sample -Limited geographic representation in high-income setting	Level III, Quality B
10	Gomes, et al., 2017	Observational	-Review of pregnancy-related eligibility criteria of 16 therapeutic and vaccine studies in Ebola-affected countries -Outbreak(s): Ebola in West Africa (2014-2016)	-All 13 studied drug and vaccine trials excluded pregnant women -Two out of three convalescent plasma studies included pregnant women -Information on pregnancy status was not routinely collected	-Drug and vaccine trials – proposed, initiated or completed-- and their pregnancy-related eligibility criteria	-Potential for limited and missing data	Level III, Quality B
11	Gould, et al., 2021	Observational	-Review of research modifications implemented at a research institute in Australia conducting research on pregnant women -Outbreak(s): COVID-19 global pandemic (2020)	-Online recruitment of pregnant subjects, electronic consent, virtual interviews, distribution of study products by mail, use of personal protective equipment, shorter interviews, increased hygiene, and COVID screening for in-person meetings	-Modified practices for safely conducting perinatal research during the COVID-19 pandemic	-Authors note that technologies used for remote research are in the early stages of adoption -Recruitment and data collection strategies may influence participant characteristics	Level III, Quality B
12	Jaffe, et al., 2020	Qualitative	-Semi-structured in-depth interviews with pregnant and recently pregnant women (n = 13) in the U.S. -Outbreak(s): Zika (hypothetical)	-Participation depended upon three main factors: existing evidence, risk of harm to the baby, and trust of their provider and the medical establishment in general	-Perspectives on participation in hypothetical vaccine trials -Decision-making processes around participation	-Authors note a small, homogeneous sample and brief interviews	Level III, Quality B
13	Kissler, et al., 2022	Observational	-Review of research modifications implemented by 5 academic centers conducting perinatal research in the United States from Mar-May 2020 -Outbreak(s): COVID-19 global pandemic (2020)	-Online recruitment, virtual enrollment and consent, qualitative data collection via video conferencing, use of smartphone technology, wearable biological measurement, and participant self-collection of samples -Increased access to underrepresented populations	-Modified practices to safely conduct perinatal research during the COVID-19 pandemic	-Limited geographic representation in a single high-income setting	Level III, Quality B
14	Knight, et al., 2020	Expert opinion	-Advocacy paper addressing safety concerns and changing attitudes toward inclusion -Outbreak(s): COVID-19 global pandemic (2020)	-Researchers must step out of their comfort zone to change the default -The RECOVERY trial provides a template for the inclusion of pregnant women in other studies	-Safety concerns, changing attitudes	-Potential for author bias	Level V, Quality B
15	Kons, et al., 2022	Observational	-Online registry search of international clinical trials database (www.clinicaltrials.gov) using the search terms “COVID-19 and vaccine” from May-Oct 2020, yielding 90 vaccine trials and 495 treatment trials - Outbreak(s): COVID-19 global pandemic (2020)	- Of 90 vaccine trials, 88 (97.8%) excluded pregnant individuals - Of the 495 treatment trials, 350 (70.7%) excluded pregnant individuals -25% of trials required contraception	-Rates of exclusion for pregnant women in vaccine and treatment trials -Requirements for contraception in pregnancy-capable participants	-Study limited to trials available in single registry	Level III, Quality B
16	Malhamé, et al., 2020	Expert opinion	-Advocacy paper about the moral imperative to include pregnant women in clinical trials -Outbreak(s): COVID-19 global pandemic (2020)	-Moral obligation to protect women through research, rather than from research	-Need to adapt current clinical trials to include pregnant women	-Potential for author bias	Level V, Quality B
17	Marban-Castro, et al., 2021	Qualitative	-Semi-structured interviews with 24 pregnant women and 6 healthcare providers of pregnant women in Spain from June-Oct 2020 -Outbreak(s): COVID-19 global pandemic (2020)	-Willingness to participate in a clinical trial among pregnant women was low (16.7%), and did not depend on which drug was being tested -Fears of adverse effects on the fetus was the principal concern -More likely to participate in trials if a personal safety benefit was perceived	-Participants’ understanding of and potential enrollment in COVID-19 clinical trials	-Authors noted the potential for desirability bias -Small sample size restricted to a single geographic region	Level III, Quality B
18	Minchin, et al., 2023	Systematic review of observational studies	-Vaccine phase II and III clinical trials during outbreaks from 2009-2019, registry search of 18 clinical trial registries globally, yielding 84 results -Outbreak(s): H1N1 influenza, Middle East Respiratory Syndrome Coronavirus, Zika, and Ebola	-Pregnant women were excluded from >80.0 % of emergency vaccine clinical trials -8 clinical trial protocols explicitly included pregnant women -Less than 3% of studies monitored and reported incidental pregnancies -Addresses gaps in existing guidance for inclusion of pregnant women	-Eligibility criteria -Pregnancy outcomes -Gaps in existing guidance	-Limited to studies written in English -Authors noted limitations and gaps in available data	Level III, Quality B
19	Mourad, et al., 2020	Expert opinion	-Advocacy paper for the inclusion of pregnant women in COVID-19 research -Outbreak(s): COVID-19 global pandemic (2020)	-42 of 2100 clinical trials during COVID-19 are being conducted in pregnancy -Less than 2% of current COVID-19 trials include pregnant women -Recommend flexibility in approval processes, collaboration, allowing virtual consent	-Impact of COVID-19 on ongoing and new pregnancy research -Challenges, key strategies necessary	-Potential for author bias	Level V, Quality B
20	The Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (Prevent Working Group, 2021)	Consensus panel	-Recommendations from the Prevent Working Group -Outbreak(s): emerging epidemic threats globally	-Stronger surveillance systems with relevant maternal health data -Research should include pregnant women, be developed ahead of outbreaks, include specific recommendations for use in pregnancy, with pregnancy-specific adverse effects -Suitability in pregnancy should guide vaccine investment decisions -Informed consent for participation, including during outbreaks, consider perspectives of pregnant women and maternal health experts in vaccine development	-22 key recommendations for incorporating the interests of pregnant women in vaccine research for emerging pathogens	-Potential for author bias	Level IV, Quality B
21	Smith, et al., 2020	Observational	-Online registry search of the WHO ^§ International Clinical trials registry platform (18 registries) for COVID-19-related trials in April 2020, yielding 927 results -Outbreak(s): COVID-19 global pandemic (2020)	-52% explicitly excluded pregnancy, 46% failed to address pregnancy at all -16 trials were pregnancy-specific, only 3 were randomized controlled trials -Only 2 drug trials included pregnant women -688 (74.2%) of COVID-19 trials were in Asia, 128 (13.8%) in Europe, and 66 (7.2%) in North America.	-Eligibility criteria for the inclusion or exclusion of pregnant women, categorized by region	-Authors noted that other relevant trials my not have been captured in this analysis -Lack of consistent search functions across databases	Level III, Quality B
22	Whitehead & Walker, 2020	Expert opinion	-Advocacy paper for the inclusion of pregnant women in COVID-19 research -Outbreak(s): COVID-19 global pandemic (2020)	-Advocacy groups and professional organizations must press for the safe inclusion of pregnant women in clinical trials for COVID-19 therapeutics and vaccines	-Historical and ethical arguments for inclusion	-Potential for author bias	Level V, Quality B
23	World Health Organization, 2020	Consensus panel	-Guidelines for the management of pregnant and breastfeeding women in the context of Ebola virus disease, Feb 2020 -Outbreak(s): Ebola virus globally	-Recommends that pregnant women be included in clinical trial vaccine research with provisions for safety monitoring and case documentation, with follow-up of pregnant women and their offspring -Recommends offering the use of investigational therapies for pregnant women with Ebola in the context of rigorous research and following the MEURI ^‡ protocol	-Key recommendations for the management of pregnant women in the context of Ebola	-Authors noted the very low quality of existing evidence	Level IV, Quality B

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