key: cord-0784083-0cww1q5p authors: Sainz Bueno, José Antonio; Cerrillos González, Lucas; Abascal-Saiz, Alejandra; Rodríguez Gallego, María Victoria; López Pérez, Rocío; Fernández Alonso, Ana María; de la Cruz Conty, Maria Luisa; Alonso Saiz, Rubén; Molina Oller, Magdalena; Cruz-Santamaría Ortiz, Amparo; Martínez-Pérez, Óscar title: Association of ABO and Rh Blood Groups with obstetric outcomes in SARS-CoV-2 infected pregnancies: A prospective study with a multivariate analysis date: 2021-07-07 journal: Eur J Obstet Gynecol Reprod Biol DOI: 10.1016/j.ejogrb.2021.07.008 sha: ac20bb87e9528be62f889c0ad26b9e81b77a71cb doc_id: 784083 cord_uid: 0cww1q5p OBJECTIVE: To evaluate the influence of ABO and Rh blood groups on morbidity among SARS-CoV-2 infected pregnancies. DESIGN: Prospective observational study. SETTING: 78 centers of the Spanish Obstetric Emergency Group. POPULATION: Pregnant women with SARS-CoV-2 tested with polymerase-chain-reaction between 26-February and 5-November, 2020. A cohort of 1,278 SARS-CoV-2(+) pregnant women was analyzed and a concurrent comparison group of 1,453 SARS-COV-2(-) patients was established. METHODS: Data were collected from medical charts. SARS-COV-2(+) was compared with SARS-COV-2(-) for differences in distribution of blood groups. We performed multivariate analysis, controlling for maternal age and ethnicity, to evaluate association of ABO and Rh blood groups with maternal and perinatal outcomes in SARS-CoV-2(+) patients with adjusted odds ratios (aOR) and 95% confidence intervals (CI). MAIN OUTCOMES MEASURES: Medical morbidity: Symptomatic COVID-19 and medical complications. Obstetric outcomes: caesarean delivery, preterm deliveries, preterm premature rupture of membranes (PPROM), hemorrhagic events, pre-eclampsia, maternal and neonatal mortality, stillbirth. RESULTS: Differences were noted between blood types and Rh for age and ethnicity comparing SARS-CoV-2(+) and SARS-CoV-2(-) groups (p<0.05). Among the SARS-CoV-2(+) cohort, the odds of symptomatic COVID-19 and obstetric hemorrhagic event were higher in Rh+ vs Rh- mothers (aOR 1.48, 95% CI 1.02-2.14, p=0.037, and aOR 8.72, 95% CI 1.20-63.57, p=0.033, respectively), and PPROM were higher among blood type A vs non-A mothers (aOR 2.06, 95% CI 1.01-4.18, p=0.046). CONCLUSIONS: In SARS-CoV-2(+) pregnant women, Rh- status was associated with a lower risk of symptomatic COVID-19, while Rh+ and blood group A were associated with obstetric hemorrhage and PPROM, respectively. TWEETABLE ABSTRACT: Among pregnant women with SARS-CoV-2, blood group A and Rh+ are associated with medical and obstetric morbidity. Several risk factors for COVID-19 infection, morbidity, and mortality are now known, including age, sex, and a number of chronic conditions (hypertension, diabetes, cardiovascular and respiratory diseases) and laboratory findings 12, 13 . Additionally, the presence of severe symptoms is associated with a higher risk of complications and mortality from COVID-19 compared to mild symptoms, both in general population 13 and in pregnant women 14 . Recently, it has been reported that the association between ABO blood groups and COVID-19 infection, severity and demise exists in such a way that there is a greater risk of infection and severity in individuals with type A blood whereas there is a lower risk in type O blood groups [15] [16] [17] [18] . We evaluated the influence of the ABO and Rh blood group on COVID-19 and obstetric morbidity in a pregnancy cohort of SARS-CoV-2 positive mothers. type distribution. Non-infected patients were those defined by a negative PCR at admission on delivery ward. Each center identified 1-2 PCR negative pregnancies delivered immediately before and/or after delivery of each SARS-CoV-2 infected mother, regardless of the outcome. This method of identifying mothers not exposed to SARS-CoV-2 infection was deployed to adjust for center conditions at the time of delivery and decreased the risk of bias. Hospitals collected the encoded information in two separate phases: during the enrolment period that occurred at the time of the SARS-CoV-2 test during pregnancy and within 6 weeks after birth. Information regarding the demographic characteristics of each pregnant woman, comorbidities and current obstetric history was extracted from the clinical history and from the interview with the patient; subsequently, age and race were categorized following the classification used by the CDC 22 A cohort of 1,278 SARS-CoV-2(+) pregnant women was analyzed ( Figure S1 ) Table 2 , whereas medical, obstetric and neonatal morbidity are compiled in Table 3 This is the first prospective study with multivariable analysis to evaluate the association of ABO and Rh blood group with medical and obstetric morbidity in SARS-CoV-2 infected mothers. We found that the Rh-status was associated with a lower risk of symptomatic COVID-19 after adjusting for maternal age and ethnicity. In terms of perinatal outcomes, blood group A was associated to PPROM, and regarding obstetric complications Rh+ patients developed more hemorrhagic events, in particular, more postpartum hemorrhage. The main strength of our work is the large cohort of SARS-CoV-2 positive deliveries (1,287) from 78 centers across Spain, adding to the reliability and generalizability of its findings. Our blood type comparison group was representative since was is not a historical cohort but a group of pregnant patients recruited from the same hospitals and at the same time as the SARS-CoV-2 positive group. It has been suggested that ABO blood group system is related to many bacterial and viral infections, such as helicobacter pylori, norovirus, HBV, SARS-CoV and MERS- Recently, several studies about COVID-19 in China and America discovered relationships between ABO blood group and COVID-19 infection, severity and demise in general population [15] [16] [17] [18] . About the association between ABO blood groups and infectivity due to SARS-CoV-2, initial studies assessed a greater risk of infectivity in the A blood group [15] [16] [17] [18] and that O blood group protects from infection 15, 16, 18, 31 . However, Dzilk et al. 32 performed a re-evaluation of the data from those studies and did not observe an association between the ABO blood groups and the risk of infection by SARS-CoV-2. There is even greater controversy between the association of the ABO blood group and COVID-19 severity and mortality. According to Wu et al. 15 , AB blood group is associated with greater severity and mortality, while Zhao et al 17 A blood group is the one with the greatest association with severity of the disease. Nevertheless, different authors agreed that the O blood group is the one associated to milder symptoms [15] [16] [17] [18] 31 . These associations are not causal, and need further investigation. In our study, we found the presence of Rh-status protective in terms of development of COVID-19 after adjusting for maternal age and ethnicity, in line with Ray et al findings 31 . In terms of obstetric outcomes, blood group A was associated to PPROM. Willebrand factor is known in non-O blood group 42 , especially A blood group 42 , and this situation favors the presence of arterial and venous thrombosis 43 . Finally, there seems to be an association between the presence of no O blood group (particularly the A1A1 / A1B / BB groups) and the risk of venous thrombosis 42, 44 . According to our study the presence of Rh-status was protective in terms of development of symptomatic COVID-19 after adjusting for maternal age and ethnicity. In terms of perinatal and obstetric outcomes, blood group A was associated to PPROM and Rh + patients developed more hemorrhagic events, in particular, more postpartum hemorrhage. Figure S1 . Flow chart of the study data. Table S1 . List of hospitals contributing to the study (n=78). Montse Macià (Hospital Universitari Arnau de Vilanova), Laia Pratcorona (Hospital Universitari Germans Trias i Pujol) Lourdes Martín González (Hospital Joan XXIII de Tarragona) María Joaquina Gimeno Gimeno (Hospital Universitario Reina Sofía) Mónica Catalina Coello (Hospital Virgen Concha de Zamora) Hospital del Mar) María Begoña Encinas Pardilla A novel coronavirus from patients with pneumonia in China Panel Covid-19 en España Stockholm: European Centre for Disease Prevention and Control Clinical Characteristics of Pregnant Women with Covid-19 in Wuhan, China COVID-19) in A report based on 116 cases Lei Z; sixth batch of Anhui medical team aiding Wuhan forCOVID-19. Coronavirus disease 2019 in pregnancy executive management summary and short report of outcome COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals Meaney-Delman D; CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team. 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Chin Functionally important glycosyltransferase gain and loss during catarrhine primate emergence Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis ABO blood group system, age, sex, risk factors and cardiac infarction ABO(H) blood groups and vascular disease: a systematic review and meta-analysis Data are shown as n (% of total). In bold: statistical significant differences between blood groups. a Group non-A: AB+B+O blood types b Group non-O: A+AB+B blood types *Odds Ratio adjusted for maternal age and ethnicity. PROM: Premature rupture of membranes; PPROM: Preterm Premature Rupture of Membranes; TE events: Thromboembolic events; ICU: Intensive Care Unit. § Poisson regression modelling, adjusting for maternal age and ethnicity, was also applied: Hemorrhagic events aIRR= 8.21 (1.14-59.31), p-value= 0.037; Postpartum hemorrhage aIRR= 7.15 (0.99-51.77), p-value= 0.052.