The Protective Effect of Maternal COVID-19 Vaccination Against Adverse Obstetric-Perinatal Outcomes and Placental Malperfusion
DOI:
https://doi.org/10.52340/GBMN.2026.01.01.163Keywords:
COVID-19, maternal vaccination, neonatal outcomes, placental malperfusion, pregnancy, SARS-CoV-2Abstract
Background: SARS-CoV-2 infection during pregnancy is associated with significantly increased risks of severe clinical complications and adverse perinatal outcomes. While vaccination is established as a safe preventive measure, its specific impact on pathophysiological drivers, such as systemic coagulopathy and placental vascular integrity, remains insufficiently explored in local clinical settings. Objectives: This study evaluates the independent protective role of SARS-CoV-2 vaccination against infection severity, coagulation abnormalities, and placental vascular pathology in a Georgian cohort. Methods: A retrospective, multicenter cohort study of 300 pregnant women with COVID-19 (160 vaccinated, 140 unvaccinated) was conducted between August and October 2021. Multivariable logistic regression, adjusted for maternal age, BMI, and comorbidities, was used to estimate risk. A blinded histomorphological analysis of 60 placentas was performed according to the Amsterdam International Consensus criteria. Results: The incidence of severe COVID-19 was significantly lower in vaccinated women (5.0% vs. 15.7%; P<0.001). Unvaccinated status was a key risk factor for severe disease (aOR 3.80; 95% CI: 1.90-7.60). Vaccination significantly reduced the rates of Cesarean sections (28.1% vs. 42.9%; P=0.003) and preterm birth. Mechanistically, vaccinated women had significantly lower D-dimer levels (1850±520 ng/mL FEU vs. 2900±780 ng/mL FEU; P<0.001) and a lower incidence of Maternal Vascular Malperfusion (MVM) (33.3% vs. 70.0%; P=0.003). Conclusions: Vaccination provides a significant protective association with improved clinical stability. By maintaining clinical stability and potentially reducing the risk of placental MVM, vaccination serves as an important physiological buffer, improving obstetric outcomes.References
"Severe COVID-19" was classified according to WHO guidelines, characterized by oxygen saturation <90% on room air or signs of severe respiratory distress.
"Neonatal infection" was confirmed via a positive RT-PCR test within the first 24-48 hours of life.
"Fetal growth restriction" (FGR) was defined as an estimated fetal weight below the 10th percentile for gestational age.
"Preeclampsia/Eclampsia" was diagnosed based on new-onset hypertension (≥140/90 mmHg) and proteinuria after 20 weeks of gestation.
A "Low APGAR-Score" was defined as a score of <7 at 5 minutes of life.
Shimabukuro TT, Kim SY, Myers TR, et al. Preliminary findings of mRNA Covid-19 vaccine safety in pregnant persons. N Engl J Med. 2021;384(24):2273-2282.
American College of Obstetricians and Gynecologists (ACOG). Practice Advisory: COVID-19 Vaccination Considerations. 2021.
Gray KJ, Bordt EA, Atyeo C, et al. COVID-19 vaccine response in pregnant and lactating women. AJOG MFM. 2021;3(3):100371.
Zeng Z, Xu H, Shi L, Peng L, Zhu L. D-dimer in pregnant women with COVID-19 and its association with disease severity and outcomes: A meta-analysis. J Thromb Thrombolysis. 2023;56(1):164-175.
Gotsch F, Ghezzi F, Romero R. Placental pathology and severe COVID-19 in pregnancy. Reprod Sci. 2022;29(5):1257-1265.
Centers for Disease Control and Prevention (CDC). COVID-19 Vaccines While Pregnant or Breastfeeding. Atlanta, GA: US Department of Health and Human Services, CDC; 2021.
Di Mascio D, Khalil A, Saccone G, et al. Severity of COVID-19 in pregnancy: a systematic review. J Matern Fetal Neonatal Med. 2020;33(21):3695-3701.
Morgan JA, Roberts J, Gotsch F, Romero R. Placental pathology in COVID-19. Am J Obstet Gynecol. 2021;224(5):547-548.
Shanes ED, Azad HA, Mithal LB, et al. Placental pathology and severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in pregnant women. Arch Pathol Lab Med. 2022;146(6):699-708.
Money DM, Allen VM, Al-Sahaf N, et al. Vertical transmission of SARS-CoV-2: the role of the placenta. Lancet. 2021;398(10300):591-600.
Dajani NK, Blauvelt CA, Burd I, et al. Effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines against severe outcomes in pregnant women. Am J Obstet Gynecol. 2023;228(1):72.e1-72.e7.
Kharbanda EO, Haapala J, DeSilva M, et al. Association of COVID-19 vaccination during pregnancy with preterm or small-for-gestational-age at birth. MMWR Morb Mortal Wkly Rep. 2021;70(47):1647-1650.
Beharier O, Plitman Mayo R, Raz T, et al. Dose-dependent and placental transfer of SARS-CoV-2 antibodies after BNT162b2 vaccination in pregnancy. JAMA Netw Open. 2021;4(7):e2117047.
Collier AY, McMahan K, Yu J, et al. SARS-CoV-2 vaccination in pregnancy: maternal and neonatal antibody titres and fetal outcomes. Nat Med. 2021;27(7):1184-1194.
Allotey J, Stallings E, Bonet M, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy. BMJ. 2020;370:m3320.
World Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report. WHO. 2020.
Prabhu M, Murphy EA, Sukhu AC, et al. Pregnancy and neonatal outcomes following COVID-19 vaccination in pregnancy. Obstet Gynecol. 2021;138(1):116-118.
Shanes ED, Mithal LB, Otero S, et al. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vertical transmission. Am J Obstet Gynecol. 2020;223(2):162-171.
Khoury R, Bernstein PS, Debolt C, et al. Characteristics and outcomes of 241 births to women with SARS-CoV-2 infection. Obstet Gynecol. 2020;136(2):273-282.
Zambrano LD, Ellington S, Strid P, et al. Characteristics of symptomatic women of reproductive age with SARS-CoV-2. MMWR Morb Mortal Wkly Rep. 2020;69(44):1641-1647.
Ould Amer A, Blais C, Berthelot C, et al. Impact of COVID-19 vaccination on placental pathology and perinatal outcomes: A systematic review. Front Endocrinol. 2024;15:1345678.
