A systematic review of maternal and perinatal health outcomes in the context of epidemic threats: towards the development of a core outcome set.

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Agustina Mazzoni, Mabel Berrueta, Magdalena Babinska, Carolina Nigri, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4607012/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective To systematically identify and classify maternal and perinatal health outcomes reported in research conducted in the epidemic and pandemic context. Study design and Setting We conducted a systematic review following Cochrane Methods. We searched MEDLINE, EMBASE, LILACS, SCI-EXPANDED, CINAHL, Cochrane Central Register of Controlled Trials, PsycINFO, AMED, ClinicalTrials.gov and ICTRP, between January 2015 and March 2023. Experimental, quasi-experimental, observational studies, phase IV trials, and post-marketing studies, published protocols and ongoing registered studies reporting maternal and perinatal health outcomes were included. Studies only reporting coverage of interventions, access to routine health services, clinical presentation of infectious diseases, and reviews were excluded. A sampling strategy was used for COVID-19 studies, due to their very high numbers. Outcome verbatims were extracted and categorized in unique outcome, and further classified into domains and subdomains. Frequency of outcome reporting was calculated. Results 94 maternal and pregnancy and 47 unique neonatal outcomes were identified, from a total of 917 and 657 verbatims, respectively, reported across 440 included studies. At least 20% of included studies reported maternal and pregnancy outcomes of mode of delivery (56.1%), stillbirth (33.0%), preterm birth (28.6%), hypertensive disorders of pregnancy (26.6%), and maternal death (20.7%). These outcomes were identified across all three types of studies identified (epidemiological, product development or post-authorization surveillance). Gestational age at birth (29.8%), congenital malformations of the nervous system (26.1%), birth weight (23.4%), neonatal admission to intensive care unit (23.2%), and neonatal death (19.1%) were the most frequently reported neonatal outcomes. Conclusions Our study provides the basis for developing a core outcome set to measure maternal and perinatal health during outbreaks, which would help improve data collection of harmonized data, data synthesis, and timely development of informed public health guidance and clinical care responding to the needs of pregnant women. . Obstetrics & Gynecology Maternal & Fetal Medicine Infectious Diseases Epidemiology Maternal Pregnancy newborn epidemics pandemic systematic review Figures Figure 1 Figure 2 1. Introduction Inthe last decades, the world has witnessed a wave of outbreaks of infectious diseases with an epidemic and pandemic potential [ 1 ]. Pregnant and recently pregnant women, and their offspring (neonates, fetuses, and embryos), have often been negatively impacted by direct and indirect effects of outbreaks of respiratory diseases [ 2 – 5 ], zoonosis [ 6 ], and vector-borne diseases [ 7 ]. Outbreaks may directly increase the risk of severe maternal and perinatal morbidity or mortality [ 3 – 5 , 7 , 8 ]. In addition, decreased access to routine and emergency health services, and the social and economic burdens of outbreaks, indirectlyaffects the health and well-being of women and their offspring, particularly in resource-limited settings [ 6 , 9 , 10 ]. However, the process of generating relevant scientific evidence on effects of outbreaks, epidemics and pandemics on maternal and perinatal health generally lags behind [ 11 , 12 ]. Wide variations in how health outcomes are defined, measured and reported across studies significantly limits researchers’ ability to compare and interpret findings and to draw reliable conclusions [ 13 – 15 ]. This, in turn, represents a substantial barrier to translating research into public health interventions and clinical practice. As a result, decision-makers, healthcare providers, pregnant women and their families lack the necessary information to make informed decisions on maternal and perinatal care [ 16 ]. Timely generation and use of evidence could be facilitated by a set of core outcomes for measuring maternal and perinatal health during outbreaks, epidemics or pandemics. A core outcome set represents a minimum dataset, developed following robust consensus methods, ideally informed by a systematic review, that should be used in clinical trials, or other types of studies pertaining to specific areas of research, for measuring and reporting health outcomes that are relevant to healthcare providers, service users, and others involved in the decision-making process [ 17 ]. Available literature presents a combination of systematic reviews and consensus-building processes used to harmonize pregnancy and child outcomes for monitoring safety of novel vaccines during pregnancy, mainly related to COVID-19 vaccination in low- and middle-income countries (LMICs) [ 18 – 23 ]. So far, no unified set of outcomes has been proposed for maternal and perinatal research conducted during emerging and ongoing epidemic threats. To be better prepared for the next epidemic threat, having a core set of outcomes for measuring maternal and perinatal health in all research studies is not only desirable, but also necessary [ 12 ]. This systematic review aims to identify and classify maternal and perinatal health outcomes reported in the scientific literature, in view of informing development of a core outcome set for maternal and perinatal health during epidemic threats. 2. Material and Methods We conducted a systematic review following Cochrane Methods [ 24 ]; and results have been reported complying the recommendations of PRISMA statement 2020 [ 25 ].The systematic review has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the ID = CRD42023423196 ). The project was also registered in the Core Outcome Measures in Effectiveness Trials (COMET) initiative . 2.1 Inclusion and exclusion criteria We included studies reporting any maternal and perinatal outcomes, including health outcomes (physical, psychological, efficacy/effectiveness, and safety outcomes pertaining to both therapeutic and preventive interventions, and obstetric/clinical management) of infected and non-infected pregnant women and their offspring (neonates, fetuses, and embryos). All study designs were considered for inclusion: experimental, quasi-experimental, comparative, or non-comparative observational studies, case series, phase IV trials, and post-marketing studies, with a sample size of at least 50 subjects. The same specifications were applied to published protocols and ongoing registered studies. We excluded articles reporting only outcomes related to coverage and access to routine health services or process outcomes (e.g., number of prenatal visits), clinical presentation of symptomatic infectious diseases or risk factors of diseases. We also excluded literature reviews, systematic reviews, and overviews. Systematic reviews served mainly as sources of relevant primary studies. 2.2 Search strategy The search strategy was developed by the review team and an experienced health sciences librarian. It covered the period between 01 January 2015 and 24 March 2023 and was performed using the following electronic databases: MEDLINE, EMBASE, Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded (SCI-EXPANDED), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane Central Register of Controlled Trials, PsycINFO, AMED, ClinicalTrials.gov website and International Clinical Trials Registry Platform (ICTRP). No language restrictions were applied. The full details of the search strategy can be found in Supplement A. 2.3 Selection of studies and data extraction Pairs of review authors (FS, VO, CN, MBa) independently screened titles and abstracts yielded by the search and assessed them against the inclusion and exclusion criteria. After retrieving all potentially relevant full-text studies, the same pairs of review authors independently selected full texts and documented ineligible studies and the reasons for their exclusion. Disagreements were resolved through discussions among members of the review team. The entire process was performed using the web-based software COVIDENCE (Innovation VH. Covidence systematic review software. Melbourne, Australia; 2019). A data extraction tool was developed, considering a wide diversity of outcomes to be explored, and used to extract data from the selected full-text articles. The data extraction tool was piloted using a sample of ten studies and refined further during the extraction process. The abovementioned pairs of review authors independently extracted all included studies. Any disagreements on data extraction were resolved by consensus among the members of the review team. Each study was assigned its unique identification number and the following information was extracted: first author, year of publication, sample size of pregnant, non-pregnant and neonatal population, study period, geographical coverage (countries covered, region), type of study (epidemiological/burden of disease, product development or post-authorization surveillance), infectious disease, mode of transmission (respiratory [COVID-19 and influenza], hemorrhagic fever zoonosis [Ebola and Rift Valley fever], foodborne/waterborne [cholera], and vector-borne [zika, chikungunya, dengue, yellow fever]), and type of outcome (maternal and pregnancy, including outcomes related to childbirth and postnatal care, and neonatal), and verbatims of all reported outcomes. 2.4 Study sampling Before assessing full-text eligibility, a sampling strategy was used for COVID-19 studies, due to their very high numbers (n = 1804). Studies were excluded if abstract or country data were not available in the abstract (n = 577). Studies were subsequently included following these criteria: 1) all multi-country studies; 2) all intervention studies; 3) all studies if the number of studies per country was less than 10; 4) a random sample of 10 studies of non-interventional studies if the number of studies per country were more than 10. After the sampling described, 230 out of 737 studies from HICs and 197 out of 449 from LMICs were included. This approach allowed for limiting overrepresentation of respiratory disease outcomes or data from certain countries, as well as aided in optimizing the use of time and resources available to conduct the review. We did not envisage to exclude studies based on quality, therefore did not assess the risk of bias of studies or quality of the outcome reporting (Fig. 1). Figure 1. Sampling strategy 2.5 Analysis First, outcome verbatim homophones (different spelling of the same word) and synonyms pertaining to the same concept were categorized as one unique outcome (e.g., stillborn and fetal death were grouped under the outcome “stillbirth”). Then, unique outcomes were classified into domains and subdomains (Box 1), using a simplified domain classification based on the most recent recommendations of COMET 2018 [ 26 ]. The proportion of studies per type of study, country and region, infectious disease and mode of transmission were calculated, as well as frequency of maternal and neonatal outcomes. 3. Results The initial search yielded 9067 studies. After removing duplicates 8779 studies were screened by title and abstract, and 1976 studies were identified as relevant. Following the sampling process for COVID-19 studies described above, 1335 studies were further excluded. Subsequently, 641 studies underwent a comprehensive full-text selection, and finally, 440 studies were included. The study flow diagram is presented in Fig. 1 . Supplement B details the list of included studies, and study characteristics. Out of the included studies, 400 (90.9%) were epidemiological studies, 36 (8.2%) focused on post-authorization surveillance, and the remaining four studies (0.9%) described product developments. According to mode of transmission, respiratory diseases included a total of 351 studies (79.8%) on COVID-19, and 18 studies on influenza (4.1%). Among vector-borne diseases, zika was a subject of 55 studies (12.5%), chikungunya of six studies (1.4%), dengue of five studies (1.1%), and yellow fever of one (0.2%). Foodborne disease (cholera) was presented in two studies (0.5%), and one study each (0.2%) on hemorrhagic fever zoonosis, namely Ebola, Rift Valley fever. The total number of countries covered in our sampling was 107. In terms of regional distribution, 213 studies (38.2%) originated from the European region, 159 (28.6%) were from the Americas, 54 (9.7%) from the Eastern Mediterranean, 52 (9.3%) from the Western Pacific, 41 (7.4%) from the South-East Asia and 38 (6.8%) from the African region. Multi-country studies contributed to number of studies for each relevant region ( Table 1 ). Table 1 Characteristics of included studies Characteristics Number of studies (%) Type of study Epidemiological 400 (90.9%) Product development 4 (0.9%) Post-authorization surveillance 36 (8.2%) Countries covered Multi-country 42 (9.5%) Single country 398 (90.5%) Region* Africa 38 (6.8%) Americas 159 (28.6%) Eastern Mediterranean 54 (9.7%) Europe 213 (38.2%) South-East Asia 41 (7.4%) Western Pacific 52 (9.3%) Infectious disease by mode of transmission Airborne Covid-19 351 (79.8%) Influenza 18 (4.1%) Vector-borne Zika 55 (12.5%) Chikungunya 6 (1.4%) Dengue 5 (1.1%) Yellow fever 1 (0.2%) Hemorrhagic fevers zoonosis Ebola hemorrhagic fever 1 (0.2%) Rift valley fever 1 (0.2%) Food/water-borne Cholera 2 (0.5%) *multi-country studies contributed to more than one region where applicable We identified 917 distinct verbatims for maternal and pregnancy outcomes and further 657 neonatal outcomes, reaching respectively 1878 and 1026 verbatims, when accounting for repeated identical or similar verbatims. The complete list of verbatims ordered by unique outcome and frequency can be found in Supplement C. A total of 94 unique maternal and pregnancy outcomes and 47 unique neonatal outcomes were identified, after accounting for verbatims that covered similar concepts. Of those, 23 maternal and pregnancy outcomes ( Table 2 ) and 12 neonatal outcomes were reported in at least 5.0% of all included studies ( Table 3 ). The top ranking maternal and pregnancy outcomes were mode of delivery (247 studies; 56.1%), stillbirth (145; 33.0%), preterm birth/delivery (126; 28.6%), hypertensive disorders of pregnancy (117;26.6%), and maternal death (91 studies;20.7%).Top ranking neonatal outcomes were gestational age at birth (131 studies; 29.8%), congenital malformations of the nervous system (115; 26.1%), birth weight (103; 23.4%), admission to neonatal intensive care unit (NICU) related outbreak disease or other reason (102; 23.2%) and neonatal death (84; 19.1%). The complete lists of outcomes are presented in Supplement C . Table 2 Most commonly reported maternal and pregnancy outcomes. Maternal and pregnancy outcomes (n = 94) Studies (n) % (n/440) Mode of delivery 247 56.1% Stillbirth 145 33.0% Preterm birth/delivery 126 28.6% Hypertensive disorders of pregnancy 117 26.6% Maternal death 91 20.7% Spontaneous abortion 85 19.3% Maternal admission to intensive care unit 77 17.5% Depression 75 17.0% Anxiety 61 13.9% Gestational Diabetes Mellitus 50 11.4% Maternal hospital admission/hospital stay 43 9.8% Postpartum hemorrhage 43 9.8% Maternal mechanical ventilation 41 9.3% Premature rupture of membranes 40 9.1% Maternal confirmed infection (related outbreak disease) 36 8.2% Fetal growth restriction 33 7.5% Stress 32 7.3% Live birth 25 5.7% Pneumonia 24 5.5% Gestational age at delivery 23 5.2% Maternal oxygen support 23 5.2% Non-reassuring fetal status 22 5.0% Preterm labor 22 5.0% Note: The total number of outcomes identified was 94 in 440 studies. Most commonly reported outcomes were reported in at least 5.0% of all included studies. See complete lists of outcomes in Supplement C. Table 3 Most commonly reported neonatal outcomes. Neonatal outcomes reported (n = 47) Studies (n) % (n/440) Gestational age at birth 131 29.8% Congenital malformations of nervous system 115 26.1% Birth weight 103 23.4% Neonatal admission to intensive care unit (related outbreak disease or other reason) 102 23.2% Neonatal death 84 19.1% Size for gestational age 70 15.9% Congenital malformations of eye, ear, face and neck 55 12.5% Low or abnormal APGAR score 53 12.0% Neonatal confirmed infection (related outbreak disease) 48 10.9% APGAR score 44 10.0% Any congenital malformation(s) or birth defects (non-specified) 32 7.3% Respiratory failure 26 5.9% Note: The total number of outcomes identified was 47 in 440 studies. Most commonly reported outcomes were reported in at least 5.0% of all included studies. See complete lists of outcomes in Supplement C. Considering the reported outcomes by mode of transmission, the most frequently reported maternal and pregnancy outcome in studies of respiratory diseases (n = 369 studies) was mode of delivery (240; 65.0%), stillbirth (133; 36.3%) and preterm birth (120; 31.4%). In the group of neonatal outcomes, gestational age at birth (118; 32.5%), NICU admission (100; 27.1%), and birthweight (97; 24.7%) were the most frequently reported outcomes. Among vector-borne diseases , these were (n = 67 studies), spontaneous abortion (14; 20.9%), stillbirth (9; 13.4%), and mode of delivery (7; 10.4%). Of the neonatal outcomes, congenital malformations of the nervous system were reported 113 times, and included many different types of malformations, in a total of 67 studies (113/67). The two studies on virus zoonoses causing hemorrhagic fevers reported spontaneous abortion, with one reporting induced abortion, live birth, and stillbirth. Gestational age at birth was the sole neonatal outcome reported in these studies. In the two studies on foodborne or waterborne diseases , maternal outcomes of stillbirth and abortion, and neonatal outcomes of congenital malformations, gestational age at birth, and neonatal death were reported ( Supplement D ). Looking at the outcome distribution per type of study, a total of 95 maternal and pregnancy outcomes, and 47 neonatal outcomes were reported in epidemiological studies. By comparison, 39 maternal and pregnancy outcomes and 19 neonatal outcomes were reported in post-authorization surveillance studies. The smallest number of outcomes was found in studies on product development − 19 and 6 respectively ( Supplement E ). The top 5 reported maternal outcomes (mode of delivery, stillbirth, preterm birth / delivery, hypertensive disorders of pregnancy, maternal death) were identified across all three types of studies. Only two outcomes reported across the different types of studies were reported in less than 5% of the included studies: antenatal bleeding of unspecified etiology and spontaneous preterm birth/ delivery. Only three neonatal outcomes were reported across all types of studies, two of them among the most reported ones: neonatal death, birth weight and arterial pH at birth (< 7.0-7.2). 4. Discussion The review identified 94 maternal and pregnancy outcomes, and 47 unique neonatal outcomes heterogeneously named and described in a large number of verbatims across 440 included studies. Mode of delivery, stillbirth, preterm birth, hypertensive disorders of pregnancy, and maternal death were among the most frequently reported maternal and pregnancy outcomes. These were gestational age at birth, congenital malformations of the nervous system, birth weight, neonatal admission to intensive care units, and neonatal death among neonatal outcomes . The main strength of our study is the rigorous methods applied for conducting and reporting systematic reviews. Additionally, the external validity of our findings was expanded by the inclusion of alltypes of study designs, not only clinical trials, and use of no language restrictions. However, the review also has some limitations. The number of identified studies on effectiveness and efficacy was low, which hinders the understanding of the outcomes used in these studies, and the applicability of outcomes identified in this review to future interventional/product development studies. Furthermore, most of the studies addressed respiratory infections, mainly COVID-19 disease, which inevitably had an impact on frequency of reporting of identified outcomes, especially neonatal outcomes, which show some level of variation according to the mode of disease transmission. For COVID-19 studies, a sampling strategy was used to counteract the effect of their overrepresentation in the final list of outcomes. Although we did not formally check for saturation, a rapid exploration of COVID-19 studies not included in the review due to sampling strategy used, showed a high redundancy of outcomes. Admittedly, we could have missed some relevant studies published before 2015; but at the same time, we managed to cover several significant outbreaks that occurred in recent years, such as influenza. It should be noted that we identified a very high number of publications on COVID-19 disease which compensates for a relatively small number of included studies on other respiratory infectious disease outbreaks (e.g., Influenza 2009). There is also a possibility that we missed outcomes reported in smaller studies, that is those with less than 50 participants – and could potentially explain the very low number of studies that included covering hemorrhagic fever, zoonosis, or other recent outbreaks (e.g, Monkeypox). Finally, we failed to include studies reporting only on indirect effects of epidemics and pandemics (e.g., coverage or access to routine care such as number of prenatal visits), clinical presentation of disease – like fever, cough, headache – or risk factors. Other published COS, covering for example the COVID-19 disease and long-COVID condition, should be considered complementary to our efforts [ 27 ]. The top ranking maternal and pregnancy outcomes (mode of delivery, stillbirth, preterm birth/delivery, hypertensive disorders of pregnancy and maternal death), and neonatal outcomes (gestational age at birth, congenital malformations of nervous system, birthweight and neonatal admission to intensive care unit [related outbreak disease or other reason]) identified in this review includes outcomes commonly reported in maternal and perinatal health research, and does not reflect specific outcomes related to infectious diseases. This suggests that outcomes of interest may not depend on specific infectious diseases or mode of transmission. In fact, only a few top-rated outcomes identified in this review are disease specific or related to mode of transmission (maternal or neonatal confirmed infection and maternal pneumonia), and could indicate severity of infectious diseases (e.g., mortality, admission to ICU) or specific organ dysfunction (e.g., mechanical ventilation, need for oxygen support or respiratory failure). Although, relevance of certain outcomes may vary depending on the nature of the disease (e.g., zika infection and malformations). Surprisingly, mother-to-child transmission of infectious diseases was reported in relatively few (n = 13) studies included in the review. This could be related to challenges in defining vertical transmission early during the emergence of new infectious diseases [ 28 ]. Some of the unique pregnancy outcomes identified represent similar concepts and could be further combined. For example, spontaneous abortion/miscarriage, stillbirth, live birth, and neonatal death, represent a continuum of perinatal vital status [ 29 ]. However, depending on how studies are designed, it may not be possible to report outcomes across pregnancy trimester and after birth. This was evident during the COVID-19 pandemic where most studies covered late pregnancy and neonatal vital status, and few early pregnancy outcomes were covered [ 8 , 30 ]. Other examples of overlap include low or abnormal APGAR score, reporting of actual APGAR score values, and birth asphyxia; or size for gestational age, which requires for its computation data on gestational age and birthweight. Other outcomes reported as maternal or neonatal outcomes represent similar outcomes, the only difference being whether these were reported in the obstetric or neonatal population in the studies included in this review. For example, preterm birth/delivery, gestational age at delivery or gestational age at birth all reflect gestational age at the end of a pregnancy and could be eventually considered as a unique outcome. It is worth highlighting that among the most commonly reported outcomes were a few related to maternal mental health, such as depression, anxiety, and stress. All of these were reported in COVID-19 studies reflecting probably recent interest in maternal mental health and well-being, beyond survival and severe morbidity [ 31 , 32 ]. For neonatal outcomes, a few outcomes related to newborn care (feeding and skin-to-skin) were reported in a small number of COVID-19 studies. The same applies for other outcomes of maternal cognitive or emotional functioning. Several challenges remain unaddressed, such as the lack of comparability among studies and the difficulty in synthesizing data for meta-analyses. It is important to note that variations in reported outcomes in maternal and perinatal health are not exclusive to studies conducted in the context of epidemic threats; they have been observed across various maternal and perinatal conditions [ 33 ]. This is the case for outcomes such as stillbirths for which different gestational age and birthweight cut-off points are used, or variability in reporting vital status at birth, confounded by the need to appropriately assess gestational age at birth and birthweight. In consequence, misclassifications of perinatal status (stillbirths, live births and miscarriages) or prematurity may often occur [ 34 ]. Some other challenges relate to limited health workforce capabilities, availability of diagnostic technologies, and reporting systems, particularly in low-resource settings [ 35 , 36 ]. 5. Conclusions The findings of this review underscore the critical necessity for standardized outcomes in maternal and neonatal research, especially during times of epidemics and pandemics. It will inform the development of a standardized core outcome set (COS) for maternal and neonatal outcomes, specifically tailored for research conducted amidst ongoing and emerging epidemic threats, that our group is currently conducting. We anticipate that this review and the subsequent development of a COS will not only contribute to the harmonization of maternal and perinatal health research during epidemics, but will also have broader implications for research in these areas beyond epidemic contexts. List Of Abbreviations LMICs Low- and middle-income countries PROSPERO Prospective Register of Systematic Reviews COMET Core Outcome Measures in Effectiveness Trials LILACS Latin American and Caribbean Health Sciences Literature SCI-EXPANDED Science Citation Index Expanded CINAHL Cumulative Index to Nursing and Allied Health Literature AMED Allied and Complementary Medicine ICTRP International Clinical Trials Registry Platform FS Florencia Salva VO Vanesa Ortega CN Carolina Nigri MBa Magdalena Babinska NICU neonatal intensive care unit COS Core Sutcome set Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Availability of data and materials The datasets supporting the conclusions of this article is(are) included within the article and its additional files. Competing interests None. Funding This work was supported by the UNDP–UNFPA–UNICEF–WHO–World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Sexual and Reproductive Health and Research, WHO, Geneva, Switzerland, and the Bill and Melinda Gates Foundation (INV-041181 WHO). Author´s contribution Conceptualization: AM, MBerrueta, VP, AC, MBonet. Data curation, data analysis: MBerrueta, AM, MBabinska, AC. Formal analysis: AM, MBerrueta. Funding acquisition: MBonet. Data collection: MBabinska, FS, VO, CN. Supervision: AM, MBerrueta, VP, AC, MBonet. Writing-original draft: AM, MBerrueta, MBonet. Writing - review & editing: VP, MBabinska, CN, VO, FS, AC. All authors provided comments and approved the final manuscript. The views of the funding bodies have not influenced the content of this manuscript. 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Medicine 102:e32954. 10.1097/MD.0000000000032954 Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ et al (2019) Cochrane Handbook for Systematic Reviews of Interventions. John Wiley & Sons; Available: https://play.google.com/store/books/details?id=cTqyDwAAQBAJ Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al (2021) The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. PLoS Med 18:e1003583. 10.1371/journal.pmed.1003583 Dodd S, Clarke M, Becker L, Mavergames C, Fish R, Williamson PR (2018) A taxonomy has been developed for outcomes in medical research to help improve knowledge discovery. J Clin Epidemiol 96:84–92. 10.1016/j.jclinepi.2017.12.020 WHO Working Group on the Clinical Characterisation (2020) and Management of COVID-19 infection: A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis 20:e192–e197 Definition and categorization of the timing of mother-to-child transmission of SARS-CoV-2. World Health Organization; 7 Feb 2021 [cited 25 Feb 2024]. Available: https://www.who.int/publications/i/item/WHO-2019-nCoV-mother-to-child-transmission-2021.1 Smith ER, Oakley E, Grandner GW, Ferguson K, Farooq F, Afshar Y et al (2023) Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis. BMJ Glob Health 8:e009495. 10.1136/bmjgh-2022-009495 van Baar JAC, Kostova EB, Allotey J, Thangaratinam S, Zamora JR, Bonet M et al (2023) COVID-19 in pregnant women: a systematic review and meta-analysis on the risk and prevalence of pregnancy loss. Hum Reprod Update. 10.1093/humupd/dmad030 Behera D, Bohora S, Tripathy S, Thapa P, Sivakami M (2024) Perinatal depression and its associated risk factors during the COVID-19 pandemic in low- and middle-income countries: a systematic review and meta-analysis. Soc Psychiatry Psychiatr Epidemiol. 10.1007/s00127-024-02628-y Hale FB, Harris AL (2024) Understanding the psychological risks to maternal mental health, maternal–infant bonding, and infant development during the COVID-19 pandemic. Nurs Womens Health. 10.1016/j.nwh.2023.10.004 Duffy J, Rolph R, Gale C, Hirsch M, Khan KS, Ziebland S et al (2017) Core outcome sets in women’s and newborn health: a systematic review. BJOG 124:1481–1489. 10.1111/1471-0528.14694 Patterson JK, Aziz A, Bauserman MS, McClure EM, Goldenberg RL, Bose CL (2019) Challenges in classification and assignment of causes of stillbirths in low- and lower middle-income countries. Semin Perinatol 43:308–314. 10.1053/j.semperi.2019.03.021 Filip R, Gheorghita Puscaselu R, Anchidin-Norocel L, Dimian M, Savage WK (2022) Global challenges to public health care systems during the COVID-19 pandemic: A review of pandemic measures and problems. J Pers Med 12:1295. 10.3390/jpm12081295 Badawy SM, Radovic A (2020) Digital approaches to remote pediatric health care delivery during the COVID-19 pandemic: Existing evidence and a call for further research. JMIR Pediatr Parent 3:e20049. 10.2196/20049 Additional Declarations The authors declare no competing interests. Supplementary Files SupplementA.Searchstrategy.docx SupplementB.IncludedStudies.docx SupplementC.Verbatims.xlsx SupplementD.xlsx SupplementE.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4607012","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":319960499,"identity":"c2e50712-6009-41ee-a0d3-dff3336bb9cc","order_by":0,"name":"Agustina Mazzoni","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYBADHn5mkrVINpNsjcEBYlXyTzv8+OOPijsyxseZD378wWCTL+/A/OwDPi0St9MMDCTOPOMxO8yWLM3DkGa58QCb8Qy81txOMEgwbDsM1MJjBgyBwwaGDQzGeHXI307/cCARqMW4mf8b4w+wFvbPeLUY3M4xbDgI1GLAzMPGwAPUIs/Ag98Ww9s5xYwNZw7zSBxmM5bmMQD6jJmnGK8Wudvpm4Ehdtiev//wQyDDxkC+vX0zXi3o7gSiw6RoAAP5BpK1jIJRMApGwTAHALqhQR6oelfaAAAAAElFTkSuQmCC","orcid":"","institution":"Institute for Clinical Effectiveness and Health Policy, Emilio Ravignani 2024 (C1414CPV), Buenos Aires, Argentina","correspondingAuthor":true,"prefix":"","firstName":"Agustina","middleName":"","lastName":"Mazzoni","suffix":""},{"id":319960500,"identity":"1121fb30-3f91-40bb-a747-fe103ac5c821","order_by":1,"name":"Mabel Berrueta","email":"","orcid":"","institution":"Institute for Clinical Effectiveness and Health Policy, Emilio Ravignani 2024 (C1414CPV), Buenos Aires, Argentina. 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Introduction","content":"\u003cp\u003eInthe last decades, the world has witnessed a wave of outbreaks of infectious diseases with an epidemic and pandemic potential [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Pregnant and recently pregnant women, and their offspring (neonates, fetuses, and embryos), have often been negatively impacted by direct and indirect effects of outbreaks of respiratory diseases [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], zoonosis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and vector-borne diseases [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Outbreaks may directly increase the risk of severe maternal and perinatal morbidity or mortality [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In addition, decreased access to routine and emergency health services, and the social and economic burdens of outbreaks, indirectlyaffects the health and well-being of women and their offspring, particularly in resource-limited settings [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, the process of generating relevant scientific evidence on effects of outbreaks, epidemics and pandemics on maternal and perinatal health generally lags behind [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Wide variations in how health outcomes are defined, measured and reported across studies significantly limits researchers\u0026rsquo; ability to compare and interpret findings and to draw reliable conclusions [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. This, in turn, represents a substantial barrier to translating research into public health interventions and clinical practice. As a result, decision-makers, healthcare providers, pregnant women and their families lack the necessary information to make informed decisions on maternal and perinatal care [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTimely generation and use of evidence could be facilitated by a set of core outcomes for measuring maternal and perinatal health during outbreaks, epidemics or pandemics. A core outcome set represents a minimum dataset, developed following robust consensus methods, ideally informed by a systematic review, that should be used in clinical trials, or other types of studies pertaining to specific areas of research, for measuring and reporting health outcomes that are relevant to healthcare providers, service users, and others involved in the decision-making process [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAvailable literature presents a combination of systematic reviews and consensus-building processes used to harmonize pregnancy and child outcomes for monitoring safety of novel vaccines during pregnancy, mainly related to COVID-19 vaccination in low- and middle-income countries (LMICs) [\u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. So far, no unified set of outcomes has been proposed for maternal and perinatal research conducted during emerging and ongoing epidemic threats. To be better prepared for the next epidemic threat, having a core set of outcomes for measuring maternal and perinatal health in all research studies is not only desirable, but also necessary [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis systematic review aims to identify and classify maternal and perinatal health outcomes reported in the scientific literature, in view of informing development of a core outcome set for maternal and perinatal health during epidemic threats.\u003c/p\u003e"},{"header":"2. Material and Methods","content":"\u003cp\u003eWe conducted a systematic review following Cochrane Methods [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]; and results have been reported complying the recommendations of PRISMA statement 2020 [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].The systematic review has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eID\u0026thinsp;=\u0026thinsp;CRD42023423196\u003c/span\u003e). The project was also registered in the \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCore Outcome Measures in Effectiveness Trials (COMET) initiative\u003c/span\u003e.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Inclusion and exclusion criteria\u003c/h2\u003e \u003cp\u003eWe included studies reporting any maternal and perinatal outcomes, including health outcomes (physical, psychological, efficacy/effectiveness, and safety outcomes pertaining to both therapeutic and preventive interventions, and obstetric/clinical management) of infected and non-infected pregnant women and their offspring (neonates, fetuses, and embryos). All study designs were considered for inclusion: experimental, quasi-experimental, comparative, or non-comparative observational studies, case series, phase IV trials, and post-marketing studies, with a sample size of at least 50 subjects. The same specifications were applied to published protocols and ongoing registered studies.\u003c/p\u003e \u003cp\u003eWe excluded articles reporting only outcomes related to coverage and access to routine health services or process outcomes (e.g., number of prenatal visits), clinical presentation of symptomatic infectious diseases or risk factors of diseases. We also excluded literature reviews, systematic reviews, and overviews. Systematic reviews served mainly as sources of relevant primary studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Search strategy\u003c/h2\u003e \u003cp\u003eThe search strategy was developed by the review team and an experienced health sciences librarian. It covered the period between 01 January 2015 and 24 March 2023 and was performed using the following electronic databases: MEDLINE, EMBASE, Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded (SCI-EXPANDED), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane Central Register of Controlled Trials, PsycINFO, AMED, ClinicalTrials.gov website and International Clinical Trials Registry Platform (ICTRP). No language restrictions were applied. The full details of the search strategy can be found in \u003cb\u003eSupplement A.\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Selection of studies and data extraction\u003c/h2\u003e \u003cp\u003ePairs of review authors (FS, VO, CN, MBa) independently screened titles and abstracts yielded by the search and assessed them against the inclusion and exclusion criteria. After retrieving all potentially relevant full-text studies, the same pairs of review authors independently selected full texts and documented ineligible studies and the reasons for their exclusion. Disagreements were resolved through discussions among members of the review team. The entire process was performed using the web-based software COVIDENCE (Innovation VH. Covidence systematic review software. Melbourne, Australia; 2019).\u003c/p\u003e \u003cp\u003eA data extraction tool was developed, considering a wide diversity of outcomes to be explored, and used to extract data from the selected full-text articles. The data extraction tool was piloted using a sample of ten studies and refined further during the extraction process. The abovementioned pairs of review authors independently extracted all included studies. Any disagreements on data extraction were resolved by consensus among the members of the review team.\u003c/p\u003e \u003cp\u003eEach study was assigned its unique identification number and the following information was extracted: first author, year of publication, sample size of pregnant, non-pregnant and neonatal population, study period, geographical coverage (countries covered, region), type of study (epidemiological/burden of disease, product development or post-authorization surveillance), infectious disease, mode of transmission (respiratory [COVID-19 and influenza], hemorrhagic fever zoonosis [Ebola and Rift Valley fever], foodborne/waterborne [cholera], and vector-borne [zika, chikungunya, dengue, yellow fever]), and type of outcome (maternal and pregnancy, including outcomes related to childbirth and postnatal care, and neonatal), and verbatims of all reported outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Study sampling\u003c/h2\u003e \u003cp\u003eBefore assessing full-text eligibility, a sampling strategy was used for COVID-19 studies, due to their very high numbers (n\u0026thinsp;=\u0026thinsp;1804). Studies were excluded if abstract or country data were not available in the abstract (n\u0026thinsp;=\u0026thinsp;577). Studies were subsequently included following these criteria: 1) all multi-country studies; 2) all intervention studies; 3) all studies if the number of studies per country was less than 10; 4) a random sample of 10 studies of non-interventional studies if the number of studies per country were more than 10. After the sampling described, 230 out of 737 studies from HICs and 197 out of 449 from LMICs were included. This approach allowed for limiting overrepresentation of respiratory disease outcomes or data from certain countries, as well as aided in optimizing the use of time and resources available to conduct the review. We did not envisage to exclude studies based on quality, therefore did not assess the risk of bias of studies or quality of the outcome reporting (Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 1. Sampling strategy\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Analysis\u003c/h2\u003e \u003cp\u003eFirst, outcome verbatim homophones (different spelling of the same word) and synonyms pertaining to the same concept were categorized as one unique outcome (e.g., stillborn and fetal death were grouped under the outcome \u0026ldquo;stillbirth\u0026rdquo;). Then, unique outcomes were classified into domains and subdomains (Box 1), using a simplified domain classification based on the most recent recommendations of COMET 2018 [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The proportion of studies per type of study, country and region, infectious disease and mode of transmission were calculated, as well as frequency of maternal and neonatal outcomes.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eThe initial search yielded 9067 studies. After removing duplicates 8779 studies were screened by title and abstract, and 1976 studies were identified as relevant. Following the sampling process for COVID-19 studies described above, 1335 studies were further excluded. Subsequently, 641 studies underwent a comprehensive full-text selection, and finally, 440 studies were included. The study flow diagram is presented in \u003cb\u003eFig.\u0026nbsp;1\u003c/b\u003e. \u003cb\u003eSupplement B\u003c/b\u003e details the list of included studies, and study characteristics.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOut of the included studies, 400 (90.9%) were epidemiological studies, 36 (8.2%) focused on post-authorization surveillance, and the remaining four studies (0.9%) described product developments. According to mode of transmission, respiratory diseases included a total of 351 studies (79.8%) on COVID-19, and 18 studies on influenza (4.1%). Among vector-borne diseases, zika was a subject of 55 studies (12.5%), chikungunya of six studies (1.4%), dengue of five studies (1.1%), and yellow fever of one (0.2%). Foodborne disease (cholera) was presented in two studies (0.5%), and one study each (0.2%) on hemorrhagic fever zoonosis, namely Ebola, Rift Valley fever. The total number of countries covered in our sampling was 107. In terms of regional distribution, 213 studies (38.2%) originated from the European region, 159 (28.6%) were from the Americas, 54 (9.7%) from the Eastern Mediterranean, 52 (9.3%) from the Western Pacific, 41 (7.4%) from the South-East Asia and 38 (6.8%) from the African region. Multi-country studies contributed to number of studies for each relevant region \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of included studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of studies (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of study\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpidemiological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e400 (90.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProduct development\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-authorization surveillance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (8.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCountries covered\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMulti-country\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (9.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle country\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e398 (90.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRegion*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfrica\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (6.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmericas\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e159 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEastern Mediterranean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (9.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEurope\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e213 (38.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSouth-East Asia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (7.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWestern Pacific\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (9.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInfectious disease by mode of transmission\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAirborne\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCovid-19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e351 (79.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfluenza\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (4.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVector-borne\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZika\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChikungunya\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDengue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (1.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYellow fever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHemorrhagic fevers zoonosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEbola hemorrhagic fever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRift valley fever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFood/water-borne\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCholera\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e*multi-country studies contributed to more than one region where applicable\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe identified 917 distinct verbatims for maternal and pregnancy outcomes and further 657 neonatal outcomes, reaching respectively 1878 and 1026 verbatims, when accounting for repeated identical or similar verbatims. The complete list of verbatims ordered by unique outcome and frequency can be found in \u003cb\u003eSupplement C.\u003c/b\u003e A total of 94 unique maternal and pregnancy outcomes and 47 unique neonatal outcomes were identified, after accounting for verbatims that covered similar concepts. Of those, 23 maternal and pregnancy outcomes \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e and 12 neonatal outcomes were reported in at least 5.0% of all included studies \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e The top ranking maternal and pregnancy outcomes were mode of delivery (247 studies; 56.1%), stillbirth (145; 33.0%), preterm birth/delivery (126; 28.6%), hypertensive disorders of pregnancy (117;26.6%), and maternal death (91 studies;20.7%).Top ranking neonatal outcomes were gestational age at birth (131 studies; 29.8%), congenital malformations of the nervous system (115; 26.1%), birth weight (103; 23.4%), admission to neonatal intensive care unit (NICU) related outbreak disease or other reason (102; 23.2%) and neonatal death (84; 19.1%). The complete lists of outcomes are presented in \u003cb\u003eSupplement C\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMost commonly reported maternal and pregnancy outcomes.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal and pregnancy outcomes (n\u0026thinsp;=\u0026thinsp;94)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudies (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e% (n/440)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMode of delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e247\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStillbirth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm birth/delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertensive disorders of pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal death\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpontaneous abortion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal admission to intensive care unit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnxiety\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational Diabetes Mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal hospital admission/hospital stay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostpartum hemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal mechanical ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePremature rupture of membranes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal confirmed infection (related outbreak disease)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFetal growth restriction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStress\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLive birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal oxygen support\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-reassuring fetal status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm labor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNote: The total number of outcomes identified was 94 in 440 studies. Most commonly reported outcomes were reported in at least 5.0% of all included studies. See complete lists of outcomes in Supplement C.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMost commonly reported neonatal outcomes.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal outcomes reported (n\u0026thinsp;=\u0026thinsp;47)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudies (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e% (n/440)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongenital malformations of nervous system\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal admission to intensive care unit (related outbreak disease or other reason)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal death\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSize for gestational age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongenital malformations of eye, ear, face and neck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow or abnormal APGAR score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal confirmed infection (related outbreak disease)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPGAR score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny congenital malformation(s) or birth defects (non-specified)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNote: The total number of outcomes identified was 47 in 440 studies. Most commonly reported outcomes were reported in at least 5.0% of all included studies. See complete lists of outcomes in Supplement C.\u003c/p\u003e \u003cp\u003eConsidering the reported outcomes by mode of transmission, the most frequently reported maternal and pregnancy outcome in studies of \u003cb\u003erespiratory diseases\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;369 studies) was mode of delivery (240; 65.0%), stillbirth (133; 36.3%) and preterm birth (120; 31.4%). In the group of neonatal outcomes, gestational age at birth (118; 32.5%), NICU admission (100; 27.1%), and birthweight (97; 24.7%) were the most frequently reported outcomes. Among \u003cb\u003evector-borne diseases\u003c/b\u003e, these were (n\u0026thinsp;=\u0026thinsp;67 studies), spontaneous abortion (14; 20.9%), stillbirth (9; 13.4%), and mode of delivery (7; 10.4%). Of the neonatal outcomes, congenital malformations of the nervous system were reported 113 times, and included many different types of malformations, in a total of 67 studies (113/67). The two studies on \u003cb\u003evirus zoonoses causing hemorrhagic fevers\u003c/b\u003e reported spontaneous abortion, with one reporting induced abortion, live birth, and stillbirth. Gestational age at birth was the sole neonatal outcome reported in these studies. In the two studies on \u003cb\u003efoodborne or waterborne diseases\u003c/b\u003e, maternal outcomes of stillbirth and abortion, and neonatal outcomes of congenital malformations, gestational age at birth, and neonatal death were reported (\u003cb\u003eSupplement D\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eLooking at the outcome distribution per type of study, a total of 95 maternal and pregnancy outcomes, and 47 neonatal outcomes were reported in \u003cb\u003eepidemiological\u003c/b\u003e studies. By comparison, 39 maternal and pregnancy outcomes and 19 neonatal outcomes were reported in \u003cb\u003epost-authorization surveillance\u003c/b\u003e studies. The smallest number of outcomes was found in studies on \u003cb\u003eproduct development\u003c/b\u003e \u0026minus;\u0026thinsp;19 and 6 respectively (\u003cb\u003eSupplement E\u003c/b\u003e). The top 5 reported maternal outcomes (mode of delivery, stillbirth, preterm birth / delivery, hypertensive disorders of pregnancy, maternal death) were identified across all three types of studies. Only two outcomes reported across the different types of studies were reported in less than 5% of the included studies: antenatal bleeding of unspecified etiology and spontaneous preterm birth/ delivery. Only three neonatal outcomes were reported across all types of studies, two of them among the most reported ones: neonatal death, birth weight and arterial pH at birth (\u0026lt;\u0026thinsp;7.0-7.2).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe review identified 94 maternal and pregnancy outcomes, and 47 unique neonatal outcomes heterogeneously named and described in a large number of verbatims across 440 included studies. Mode of delivery, stillbirth, preterm birth, hypertensive disorders of pregnancy, and maternal death were among the most frequently reported maternal and pregnancy outcomes. These were gestational age at birth, congenital malformations of the nervous system, birth weight, neonatal admission to intensive care units, and neonatal death among neonatal outcomes .\u003c/p\u003e \u003cp\u003eThe main strength of our study is the rigorous methods applied for conducting and reporting systematic reviews. Additionally, the external validity of our findings was expanded by the inclusion of alltypes of study designs, not only clinical trials, and use of no language restrictions. However, the review also has some limitations. The number of identified studies on effectiveness and efficacy was low, which hinders the understanding of the outcomes used in these studies, and the applicability of outcomes identified in this review to future interventional/product development studies. Furthermore, most of the studies addressed respiratory infections, mainly COVID-19 disease, which inevitably had an impact on frequency of reporting of identified outcomes, especially neonatal outcomes, which show some level of variation according to the mode of disease transmission. For COVID-19 studies, a sampling strategy was used to counteract the effect of their overrepresentation in the final list of outcomes. Although we did not formally check for saturation, a rapid exploration of COVID-19 studies not included in the review due to sampling strategy used, showed a high redundancy of outcomes. Admittedly, we could have missed some relevant studies published before 2015; but at the same time, we managed to cover several significant outbreaks that occurred in recent years, such as influenza. It should be noted that we identified a very high number of publications on COVID-19 disease which compensates for a relatively small number of included studies on other respiratory infectious disease outbreaks (e.g., Influenza 2009). There is also a possibility that we missed outcomes reported in smaller studies, that is those with less than 50 participants \u0026ndash; and could potentially explain the very low number of studies that included covering hemorrhagic fever, zoonosis, or other recent outbreaks (e.g, Monkeypox). Finally, we failed to include studies reporting only on indirect effects of epidemics and pandemics (e.g., coverage or access to routine care such as number of prenatal visits), clinical presentation of disease \u0026ndash; like fever, cough, headache \u0026ndash; or risk factors. Other published COS, covering for example the COVID-19 disease and long-COVID condition, should be considered complementary to our efforts [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe top ranking maternal and pregnancy outcomes (mode of delivery, stillbirth, preterm birth/delivery, hypertensive disorders of pregnancy and maternal death), and neonatal outcomes (gestational age at birth, congenital malformations of nervous system, birthweight and neonatal admission to intensive care unit [related outbreak disease or other reason]) identified in this review includes outcomes commonly reported in maternal and perinatal health research, and does not reflect specific outcomes related to infectious diseases. This suggests that outcomes of interest may not depend on specific infectious diseases or mode of transmission. In fact, only a few top-rated outcomes identified in this review are disease specific or related to mode of transmission (maternal or neonatal confirmed infection and maternal pneumonia), and could indicate severity of infectious diseases (e.g., mortality, admission to ICU) or specific organ dysfunction (e.g., mechanical ventilation, need for oxygen support or respiratory failure). Although, relevance of certain outcomes may vary depending on the nature of the disease (e.g., zika infection and malformations). Surprisingly, mother-to-child transmission of infectious diseases was reported in relatively few (n\u0026thinsp;=\u0026thinsp;13) studies included in the review. This could be related to challenges in defining vertical transmission early during the emergence of new infectious diseases [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSome of the unique pregnancy outcomes identified represent similar concepts and could be further combined. For example, spontaneous abortion/miscarriage, stillbirth, live birth, and neonatal death, represent a continuum of perinatal vital status [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. However, depending on how studies are designed, it may not be possible to report outcomes across pregnancy trimester and after birth. This was evident during the COVID-19 pandemic where most studies covered late pregnancy and neonatal vital status, and few early pregnancy outcomes were covered [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Other examples of overlap include low or abnormal APGAR score, reporting of actual APGAR score values, and birth asphyxia; or size for gestational age, which requires for its computation data on gestational age and birthweight. Other outcomes reported as maternal or neonatal outcomes represent similar outcomes, the only difference being whether these were reported in the obstetric or neonatal population in the studies included in this review. For example, preterm birth/delivery, gestational age at delivery or gestational age at birth all reflect gestational age at the end of a pregnancy and could be eventually considered as a unique outcome.\u003c/p\u003e \u003cp\u003eIt is worth highlighting that among the most commonly reported outcomes were a few related to maternal mental health, such as depression, anxiety, and stress. All of these were reported in COVID-19 studies reflecting probably recent interest in maternal mental health and well-being, beyond survival and severe morbidity [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. For neonatal outcomes, a few outcomes related to newborn care (feeding and skin-to-skin) were reported in a small number of COVID-19 studies. The same applies for other outcomes of maternal cognitive or emotional functioning.\u003c/p\u003e \u003cp\u003eSeveral challenges remain unaddressed, such as the lack of comparability among studies and the difficulty in synthesizing data for meta-analyses. It is important to note that variations in reported outcomes in maternal and perinatal health are not exclusive to studies conducted in the context of epidemic threats; they have been observed across various maternal and perinatal conditions [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. This is the case for outcomes such as stillbirths for which different gestational age and birthweight cut-off points are used, or variability in reporting vital status at birth, confounded by the need to appropriately assess gestational age at birth and birthweight. In consequence, misclassifications of perinatal status (stillbirths, live births and miscarriages) or prematurity may often occur [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Some other challenges relate to limited health workforce capabilities, availability of diagnostic technologies, and reporting systems, particularly in low-resource settings [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThe findings of this review underscore the critical necessity for standardized outcomes in maternal and neonatal research, especially during times of epidemics and pandemics. It will inform the development of a standardized core outcome set (COS) for maternal and neonatal outcomes, specifically tailored for research conducted amidst ongoing and emerging epidemic threats, that our group is currently conducting. We anticipate that this review and the subsequent development of a COS will not only contribute to the harmonization of maternal and perinatal health research during epidemics, but will also have broader implications for research in these areas beyond epidemic contexts.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLMICs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLow- and middle-income countries\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePROSPERO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProspective Register of Systematic Reviews\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOMET\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCore Outcome Measures in Effectiveness Trials\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLILACS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLatin American and Caribbean Health Sciences Literature\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSCI-EXPANDED\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eScience Citation Index Expanded\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCINAHL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCumulative Index to Nursing and Allied Health Literature\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAMED\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAllied and Complementary Medicine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICTRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Clinical Trials Registry Platform\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFlorencia Salva\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVanesa Ortega\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCarolina Nigri\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMBa\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagdalena Babinska\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eneonatal intensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCore Sutcome set\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets supporting the conclusions of this article is(are) included within the article and its additional files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the UNDP\u0026ndash;UNFPA\u0026ndash;UNICEF\u0026ndash;WHO\u0026ndash;World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Sexual and Reproductive Health and Research, WHO, Geneva, Switzerland, and the Bill and Melinda Gates Foundation (INV-041181 WHO).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026acute;s contribution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: AM, MBerrueta, VP, AC, MBonet. \u0026nbsp;Data curation, data analysis: MBerrueta, AM, MBabinska, AC. Formal analysis: AM, MBerrueta. Funding acquisition: MBonet. Data collection: MBabinska, FS, VO, CN. Supervision: AM, MBerrueta, VP, AC, MBonet. \u0026nbsp; Writing-original draft: AM, MBerrueta, MBonet.\u0026nbsp;Writing - review \u0026amp; editing: \u0026nbsp;VP, MBabinska, CN, VO, FS, AC.\u003c/p\u003e\n\u003cp\u003eAll authors provided comments and approved the final manuscript. The views of the funding bodies have not influenced the content of this manuscript. \u0026nbsp;The named authors alone are responsible for the views expressed in this publication and do not necessarily represent the decisions or the policies of the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP) or the World Health Organization (WHO) or the other affiliated institutions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Dr. Karen Klein for her contributions in the presubmission inquires.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBaker RE, Mahmud AS, Miller IF, Rajeev M, Rasambainarivo F, Rice BL et al (2022) Infectious disease in an era of global change. 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JMIR Pediatr Parent 3:e20049. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2196/20049\u003c/span\u003e\u003cspan address=\"10.2196/20049\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[{"identity":"d54905e5-c234-42cd-b73b-24210893406a","identifier":"10.13039/100000865","name":"Bill and Melinda Gates Foundation","awardNumber":"INV-041181 WHO","order_by":0}],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"UNDP–UNFPA–UNICEF–WHO–World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Sexual and Reproductive Health and Research, WHO, Geneva, Switzerland","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Maternal, Pregnancy, newborn, epidemics, pandemic, systematic review","lastPublishedDoi":"10.21203/rs.3.rs-4607012/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4607012/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo systematically identify and classify maternal and perinatal health outcomes reported in research conducted in the epidemic and pandemic context.\u003c/p\u003e\u003ch2\u003eStudy design and Setting\u003c/h2\u003e \u003cp\u003eWe conducted a systematic review following Cochrane Methods. We searched MEDLINE, EMBASE, LILACS, SCI-EXPANDED, CINAHL, Cochrane Central Register of Controlled Trials, PsycINFO, AMED, ClinicalTrials.gov and ICTRP, between January 2015 and March 2023. Experimental, quasi-experimental, observational studies, phase IV trials, and post-marketing studies, published protocols and ongoing registered studies reporting maternal and perinatal health outcomes were included. Studies only reporting coverage of interventions, access to routine health services, clinical presentation of infectious diseases, and reviews were excluded. A sampling strategy was used for COVID-19 studies, due to their very high numbers. Outcome verbatims were extracted and categorized in unique outcome, and further classified into domains and subdomains. Frequency of outcome reporting was calculated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e94 maternal and pregnancy and 47 unique neonatal outcomes were identified, from a total of 917 and 657 verbatims, respectively, reported across 440 included studies. At least 20% of included studies reported maternal and pregnancy outcomes of mode of delivery (56.1%), stillbirth (33.0%), preterm birth (28.6%), hypertensive disorders of pregnancy (26.6%), and maternal death (20.7%). These outcomes were identified across all three types of studies identified (epidemiological, product development or post-authorization surveillance). Gestational age at birth (29.8%), congenital malformations of the nervous system (26.1%), birth weight (23.4%), neonatal admission to intensive care unit (23.2%), and neonatal death (19.1%) were the most frequently reported neonatal outcomes.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur study provides the basis for developing a core outcome set to measure maternal and perinatal health during outbreaks, which would help improve data collection of harmonized data, data synthesis, and timely development of informed public health guidance and clinical care responding to the needs of pregnant women. .\u003c/p\u003e","manuscriptTitle":"A systematic review of maternal and perinatal health outcomes in the context of epidemic threats: towards the development of a core outcome set.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-02 20:52:09","doi":"10.21203/rs.3.rs-4607012/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"433ea81d-ddf9-42c3-b6ad-8d1c790c1c33","owner":[],"postedDate":"July 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":33835153,"name":"Obstetrics \u0026 Gynecology"},{"id":33835154,"name":"Maternal \u0026 Fetal Medicine"},{"id":33835155,"name":"Infectious Diseases"},{"id":33835156,"name":"Epidemiology"}],"tags":[],"updatedAt":"2024-07-02T20:52:09+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-02 20:52:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4607012","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4607012","identity":"rs-4607012","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}