Maternal and neonatal biochemical sequelae following prenatal COVID-19 infection: evidence across the peripartum period
DOI:
https://doi.org/10.18203/2394-6040.ijcmph20262312Keywords:
Biochemical markers, COVID-19, Inflammation, Maternal health, Neonatal outcomesAbstract
Pregnancy is characterized by dynamic physiological, immunological, and biochemical adaptations that sustain foetal growth and maternal health. Viral infections such as COVID-19 can disrupt this equilibrium, provoking systemic inflammatory, metabolic, and coagulative responses. While clinical complications of prenatal SARS-CoV-2 infection have been widely described, evidence on biochemical sequelae across pregnancy, delivery, and postpartum remains fragmented. Therefore, this scoping review aims to map published evidence on maternal, placental, and neonatal biochemical markers following prenatal COVID-19 infection across the peripartum period. Following PRISMA-ScR guidelines, systematic searches were conducted in PubMed, Google Scholar, and Epistemonikos from January 2020 to March 2025. Observational studies examining biochemical or immunological markers among COVID-19 infected pregnant women and their offspring were included. Data were extracted using a pre-tested charting tool and narratively synthesized during pregnancy, at delivery, and postpartum. Twenty-seven studies met inclusion criteria. Elevated inflammatory, and haematological markers were consistently observed during pregnancy. Neonatal respiratory distress and multisystem inflammatory manifestations were associated with elevated inflammatory markers. Postpartum evidence suggested presence of immunoglobulins in breast milk, thus providing passive neonatal protection. Expression of placental ACE2 and TMPRSS2 suggested viral entry expression, aligning with limited evidence of vertical transmission. Prenatal COVID-19 infection led to a wide spectrum of biochemical alterations in maternal and neonatal systems. However, emerging evidence remains heterogeneous and limited beyond delivery, hence underscoring the need for longitudinal biochemical surveillance across the peripartum period.
Metrics
References
WHO. 14.9 million excess deaths associated with the COVID-19 pandemic in 2020 and 2021. Geneva: World Health Organization, 2022. Available at: https://www.who.int/news/item/05-05-2022-14.9-million-excess-deaths-were-associated-with-the-covid-19-pandemic-in-2020-and-2021. Accessed on 26 March 2026.
Kanakaiah P, Sudha M, Kumar PR, Raju SVG, Jameema MA. A comprehensive analysis of biochemical changes across trimesters and the puerperium period. Int J Acad Med Pharm. 2024;5(6):1350-5.
Wang X, Ou H, Wu Y, Xing Z. Risk of preterm birth in maternal influenza or SARS-CoV-2 infection: a systematic review and meta-analysis. Transl Pediatr. 2023;12(4):631-44. DOI: https://doi.org/10.21037/tp-23-134
Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620-9. DOI: https://doi.org/10.1172/JCI137244
Acharya D, Liu GQ, Gack MU. Dysregulation of type I interferon responses in COVID-19. Nat Rev Immunol. 2020;20(7):397-8. DOI: https://doi.org/10.1038/s41577-020-0346-x
Wastnedge EAN, Reynolds RM, Van Boeckel SR, Stock SJ, Denison FC, Maybin JA, et al. Pregnancy and COVID-19. Physiol Rev. 2021;101(1):303-18. DOI: https://doi.org/10.1152/physrev.00024.2020
Al-Qahtani AA, Alhamlan FS, Al-Qahtani AA. Pro-Inflammatory and Anti-Inflammatory Interleukins in Infectious Diseases: A Comprehensive Review. Trop Med Infect Dis. 2024;9(1):13. DOI: https://doi.org/10.3390/tropicalmed9010013
Morotti D, Tabano S, Gaudioso G, Radaelli T, Croci GA, Bianchi N, et al. In situ analyses of placental inflammatory response to SARS-CoV-2 infection in cases of mother–fetus vertical transmission. Int J Mol Sci. 2024;25(16):8825. DOI: https://doi.org/10.3390/ijms25168825
Tóth EL, Orbán-Kálmándi R, Bagoly Z, Lóczi L, Deli T, Török O, et al. Case report: Complex evaluation of coagulation, fibrinolysis and inflammatory cytokines in a SARS-CoV-2 infected pregnant woman with fetal loss. Front Immunol. 2024;15:1329236. DOI: https://doi.org/10.3389/fimmu.2024.1329236
Fernandes GM, Sasaki LMP, Jardim-Santos GP, Schulte HL, Motta F, Da Silva ÂP, et al. Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study. Front Immunol. 2023;14:1176898. DOI: https://doi.org/10.3389/fimmu.2023.1176898
Narayanaswamy V, Pentecost B, Alfandari D, Chin E, Minor K, Kastrinakis A, et al. Humoral and Cell-Mediated Immune Response in Colostrum from Women Diagnosed Positive for SARS-CoV-2. Breastfeed Med. 2021;16(12):987-94. DOI: https://doi.org/10.1089/bfm.2021.0082
Eman A, Balaban O, Kocayiğit H, Süner KÖ, Cırdı Y, Erdem AF. Maternal and neonatal outcomes of critically ill pregnant and puerperal patients diagnosed with COVID-19 disease: retrospective comparative study. J Korean Med Sci. 2021;36(44):e309. DOI: https://doi.org/10.3346/jkms.2021.36.e309
Chen G, Zhang Y, Zhang Y, Ai J, Yang B, Cui M, et al. Differential immune responses in pregnant patients recovered from COVID-19. Signal Transduct Target Ther. 2021;6(1):289. DOI: https://doi.org/10.1038/s41392-021-00703-3
Foo SS, Cambou MC, Mok T, Fajardo VM, Jung KL, Fuller T, et al. The systemic inflammatory landscape of COVID-19 in pregnancy: extensive serum proteomic profiling of mother–infant dyads with in utero SARS-CoV-2. Cell Rep Med. 2021;2(11):100453. DOI: https://doi.org/10.1016/j.xcrm.2021.100453
Liu D, Li H, Li X, Rodriguez GD, Pietz H, Fiel RH, et al. Comparative analysis of viral load and cytokines during SARS-CoV-2 infection between pregnant and non-pregnant women. Int J Mol Sci. 2024;25(14):7771. DOI: https://doi.org/10.3390/ijms25147731
Atak Z, Rahimli Ocakoglu S, Topal S, Macunluoglu AC. Increased maternal mortality in unvaccinated SARS-CoV-2 infected pregnant patients. J Obstet Gynaecol. 2022;42(7):2709-14. DOI: https://doi.org/10.1080/01443615.2022.2099255
Hughes CE, Nibbs RJB. A guide to chemokines and their receptors. FEBS J. 2018;285(16):2944-71. DOI: https://doi.org/10.1111/febs.14466
Siddiq A, D’lamanda VG, Anggi MD, Rakhmilla LE, Pramatirta AY, Pusianawati D, et al. Characteristics of COVID-19 comorbidities and severity profiles among pregnant women from a single-center cross-sectional study. Medicine. 2024;103(25):e38636. DOI: https://doi.org/10.1097/MD.0000000000038636
Craina M, Iacob D, Dima M, Bernad S, Silaghi C, Moza A, et al. Clinical, laboratory, and imaging findings of pregnant women with possible vertical transmission of SARS-CoV-2: case series. Int J Environ Res Public Health. 2022;19(17):10916. DOI: https://doi.org/10.3390/ijerph191710916
Gong XM, Song L, Li H, Li L, Jin W, Yu KH, et al. CT characteristics and diagnostic value of COVID-19 in pregnancy. PLoS One. 2020;15(7):e0235134. DOI: https://doi.org/10.1371/journal.pone.0235134
Mohr-Sasson A, Chayo J, Bart Y, Meyer R, Sivan E, Mazaki-Tovi S, et al. Laboratory characteristics of pregnant compared to non-pregnant women infected with SARS-CoV-2. Arch Gynecol Obstet. 2020;302(3):629. DOI: https://doi.org/10.1007/s00404-020-05655-7
Raoufi M, Hojabri M, Samiei Nasr D, Najafiarab H, Salahi-Niri A, Ebrahimi N, et al. Comparative analysis of COVID-19 pneumonia in pregnant versus matched non-pregnant women: radiologic, laboratory, and clinical perspectives. Sci Rep. 2024;14:22609. DOI: https://doi.org/10.1038/s41598-024-73699-9
Ozer KB, Sakin O, Koyuncu K, Cimenoglu B, Demirhan R. Comparison of Laboratory and Radiological Findings of Pregnant and Non-Pregnant Women with Covid-19. Rev Bras Ginecol Obstet. 2021;43(3):200-6. DOI: https://doi.org/10.1055/s-0041-1726054
Shmakov RG, Prikhodko A, Polushkina E, Shmakova E, Pyregov A, Bychenko V, et al. Clinical course of novel COVID-19 infection in pregnant women. J Matern Fetal Neonatal Med. 2022;35(23):4431-7. DOI: https://doi.org/10.1080/14767058.2020.1850683
Edlow AG, Li JZ, Collier ARY, Atyeo C, James KE, Boatin AA, et al. Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic. JAMA Netw Open. 2020;3(12):E2030455. DOI: https://doi.org/10.1001/jamanetworkopen.2020.30455
Bakhle A, Sreekumar K, Baracho B, Sardessai S, Silveira MP. Cavitary lung lesions in a neonate: Potential manifestation of COVID‐19 related multisystem inflammatory syndrome. Pediatr Pulmonol. 2021;57(1):311. DOI: https://doi.org/10.1002/ppul.25732
Cleland DA, Eranki AP. Procalcitonin. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.
Frenkel A, Shiloh A, Azulay B, Novack V, Klein M, Dreiher J. The role of lactate dehydrogenase in hospitalized patients, comparing those with pulmonary versus non-pulmonary infections: a nationwide study. PLoS One. 2023;18(3):e0283380. DOI: https://doi.org/10.1371/journal.pone.0283380
Ebrahim Babai M, Kabiri A, Movahedi M, Ghahiri A, Hajhashemi M, Dehghan M. Evaluation of the relationship between early clinical manifestations and changes in biochemical, inflammatory, and coagulation parameters and the prognosis of pregnant women with COVID-19 admitted to the ICU. Adv Biomed Res. 2024;13:1. DOI: https://doi.org/10.4103/abr.abr_257_23
Hong LZ, Shou ZX, Zheng DM, Jin X. The most important biomarker associated with coagulation and inflammation among COVID-19 patients. Mol Cell Biochem. 2021;476(7):2877-85. DOI: https://doi.org/10.1007/s11010-021-04122-4
Kinsey KE, Ganz E, Khalil S, Brustman L. Intraoperative coagulopathy during cesarean section as an unsuspected initial presentation of COVID-19: a case report. BMC Pregnancy Childbirth. 2020;20:387. DOI: https://doi.org/10.21203/rs.3.rs-36309/v1
Tan C, Huang Y, Shi F, Tan K, Ma Q, Chen Y, et al. C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early. J Med Virol. 2020;92(7):856-62. DOI: https://doi.org/10.1002/jmv.25871
Tjahyadi D, Irsyad BI, Pramatirta AY, Salima S, Anwar AD, Effendi JS, et al. Relationship Between D-Dimer Levels and Neutrophil-to-Lymphocyte Ratio (NLR) in Preeclamptic Pregnant Women with COVID-19: A Cohort Study. Med Sci Monit. 2023;29:e940130-1. DOI: https://doi.org/10.12659/MSM.940130
Faure-Bardon V, Isnard P, Roux N, Leruez-Ville M, Molina T, Bessieres B, et al. Protein expression of angiotensin-converting enzyme 2, a SARS-CoV-2-specific receptor, in fetal and placental tissues throughout gestation: new insight for perinatal counseling. Ultrasound Obstet Gynecol. 2021;57(2):242-7. DOI: https://doi.org/10.1002/uog.23583
Moriarty K, Yu M, Hussain N, Zgutka K, Sanders MM, Harigopal M, et al. COVID-19 and differential effects in twins: insights from placenta pathology. Placenta. 2022;124:62-6. DOI: https://doi.org/10.1016/j.placenta.2022.05.014
Cui D, Liu Y, Jiang X, Ding C, Poon LC, Wang H, et al. Single-cell RNA expression profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in human trophectoderm and placenta. Ultrasound Obstet Gynecol. 2021;57(2):248-56. DOI: https://doi.org/10.1002/uog.22186
Babal P, Krivosikova L, Sarvaicova L, Deckov I, Szemes T, Sedlackova T, et al. Intrauterine Fetal Demise After Uncomplicated COVID-19: What Can We Learn from the Case?. Viruses. 2021;13(12):2545. DOI: https://doi.org/10.3390/v13122545
Lebrão CW, Cruz MN, Silva MH da, Dutra LV, Cristiani C, Affonso Fonseca FL, et al. Early identification of IgA anti-SARS-CoV-2 in milk of mother with COVID-19 infection. J Hum Lact. 2020;36(4):609-13. DOI: https://doi.org/10.1177/0890334420960433
Al-kuraishy HM, Al-Gareeb AI, Albezrah NKA, Bahaa HA, El-Bouseary MM, Alexiou A, et al. Pregnancy and COVID-19: high or low risk of vertical transmission. Clin Exp Med. 2023;23(4):957-67. DOI: https://doi.org/10.1007/s10238-022-00907-z
Yang M, Wang Q, Song Y, Zou M, Li Y, Xu G, et al. A critical assessment of the potential vertical transmission hypotheses: Implications for research on the early-life infection with COVID-19. Placenta. 2021;115:78. DOI: https://doi.org/10.1016/j.placenta.2021.09.005
Downloads
Published
How to Cite
Issue
Section
