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COVID-19 in pregnancy

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COVID-19 in pregnancy
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COVID-19 infection in pregnancy is associated with several pregnancy complications.[1] However, pregnancy does not appear to increase the susceptibility of becoming infected by COVID-19.[1] Recommendations for the prevention of COVID-19 include the same measures as non-pregnant people.[2]

Effect of COVID-19 in pregnancy

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COVID-19 in pregnancy[1]
Complication Odds ratio 95% confidence interval
Pre-eclampsia 1.33 1.03 to 1.73
Preterm birth 1.82 1.38 to 2.39
Stillbirth 2.11 1.14 to 3.90

According to a systematic review and meta-analysis in 2021, COVID-19 is associated with stillbirth, pre-eclampsia and preterm birth.[1] According to the same review, compared with mild COVID-19, severe COVID-19 is strongly associated with preeclampsia, preterm birth, gestational diabetes and low birth weight.[1]

A review in 2022 suggests that pregnant women are at increased risk of severe COVID-19 disease, with an increased rate of being hospitalized to the intensive care unit and requiring ventilation death, but was not associated with a statistically significant increase in mortality.[3]

A systematic review update in 2022 demonstrated that pregnant women are at increased risk of severe COVID-19. It also found that risk factors for severe COVID-19 in pregnant people included high body mass index, being of an older age, being of non-white ethnic origin, having pre-existing comorbidities, having pre-eclampsia or gestational diabetes.[4][5]

A 2023 meta-analysis concluded that COVID-19 infection at any time during a pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction.[6] Unlike earlier reviews, this study did not find a link between COVID-19 infection during pregnancy and increased risk of stillbirth at or beyond 28 weeks' gestation.[6] This study used the first large set of pregnancy cohort data from sub-Saharan Africa.[6]

A marked increase in cases of situs inversus was observed several months after the lifting of the zero-COVID-19 policy in China, which coincided with a rise in infections. This rare clinical evidence suggests a possible link between infection during pregnancy and the development of this condition in the fetus, specifically during gestational weeks 4–6, the critical period for organ positioning.[7]

Effect of SARS-CoV-2 on Fetal Neurodevelopment

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Maternal infection increases the chance of neurodevelopmental disorders. The underlying mechanisms that cause this have not yet been elucidated.[8] A 2024 study found impaired cardiac function in babies whose mothers contracted COVID in the second trimester.[9]

In two systematic reviews [10][11] concluded that covid-19 could potentially disrupt the neurodevelopment of the fetus as a consequence of the hyperinflammatory host response elicited by the viral infection through various possible mechanisms. However, it is still a controversial subject due to the complex nature of investigating an unaccounted unforeseen epidemic on already pregnant women or postpartum patients.

Vertical transmission of SARS-CoV-2 directly

It is uncertain if there is a direct route of SARS-CoV-2 from the mother to the fetus, but based on some studies,[12][13] SARS-CoV-2 was present in the placental samples, amniotic fluid, or infant nasopharyngeal swabs of neonatal shows in utero infection. In a case report, it was confirmed through observing that the placental syncytiotrophoblastic cells and nasopharyngeal samples containing SARS-CoV-2 nucleocapsid proteins along with some viral substrates.[14] However, in a systematic review of systematic reviews, it is sought as a rare event.[15]

Host-virus interactions

The pro-inflammatory state could disrupt the placental development, which, in turn, results in preterm birth, preeclampsia, and restricted intrauterine growth.[16]

The Neurodevelopmental invaded by SARS-CoV-2

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The exact mechanism of how it disrupts the normal neurogenesis had brought up different hypotheses:

The direct route of transplacental transmission. Like SARS-CoV, SARS-CoV-2 might create its entry point into the brain through the ACE2 receptor. As a result of viremia, the virus binds to the endothelial ACE2 receptors of the blood brain barrier (BBB) and this way it makes its entry point into the central nervous system (CNS). This was strongly explained in a study where post-mortem brain biopsies were analyzed on electron micrography, and viral particles were evident in the frontal cortex of SARS-CoV-2 infected adults.[17] In addition, the violation of the sophisticated maternal-fetal interface by the virus could potentiate the exaggerated release of cytokines and the penetration of immune cells into the placenta and eventually to the fetus, hindering normal neurogenesis.[16]

Cholinergic Anti-inflammatory Pathway (CAP). It is suspected that the virus disrupts CAP in suppressing the release of proinflammatory cytokines, either of fetus or the mother, which triggers the hyperinflammatory state and increase risk of neurodevelopmental disorders.[16]

DNA methylation. Viral infection could alter DNA methylation patterns in genes involved with neurodevelopment.[10]

Immune system—Itself. Infected immune cells that could express the ACE2 receptor might have a role in their dissemination to the brain through different portals: vasculatures, choroid plexus, and meninges.[18]

Olfactory transport of infection. It is assumed that during laboring the offspring, neonatal infection could be acquired via direct contact with vaginal secretions or physical or airborne route. The virus binding to ACE2 receptors of the olfactory epithelium and through this channel, the virus could be able to pave its way to the CNS.[18]

Retrograde axonal transport. The gut neurons might have transported the viruses into the nervous system.[19]

Recommendations

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Prevention

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The World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) of the United States advises pregnant women to do the same things as the general public to avoid infection, such as covering cough, avoid interacting with sick people, cleaning hands with soap and water or sanitizer.[2][20]

Vaccination against COVID-19 was not associated with an increase in miscarriage or reduction in live birth.[21] Meta-analysis has not identified any pregnancy-specific safety concerns with vaccines.[22]

The data overwhelming support maternal vaccination as being effective at reducing the risk for infection and severe illness.[22]

Studies seem to show that completion of a two dose mRNA vaccination during pregnancy reduces hospital admissions for COVID-19 among infants under 6 months, but there is insufficient evidence for how long protection continues for an infant after birth.[22]

The WHO states that pregnant women can receive covid-19 vaccines and, if not already vaccinated, should have access to WHO Emergency Use Listing-approved vaccines, as the benefits of vaccination during pregnancy outweigh potential risks.[22] The Royal College of Obstetricians and Gynaecologists in the UK strongly recommend vaccination in pregnancy and prefers that the Pfizer-BioNTech or Moderna mRNA vaccines are offered where available due to greater amounts of data on that vaccine type. In America, the CDC, the American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine encourage pregnant women to get COVID-19 vaccines.[22] The Federation of Obstetric and Gynaecological Societies of India recommend vaccination, though it is not currently recommended by the Government of India.[22] More than 80 countries do not currently recommend that all pregnant and lactating women should be vaccinated.[6]

Treatment

[edit]

A state of the art review published in 2022 stated that the basic principles of diagnosing and managing COVID-19 should be the same for pregnant patients as for non-pregnant patients. It recommnended that treatment with corticosteroids should be modified to use non-fluorinated glucocorticoids and that Il-6 inhibitors and monoclonal antibodies could be used, as could specific antiviral therapies.[23]

Pregnancy is not a contraindication for therapies including respiratory support with oxygen, non-invasive ventilation, ventilation in a prone position, intubation and ventilation, and extracorporeal membrane oxygenation.[23]

See also

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References

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  1. ^ a b c d e Wei SQ, Bilodeau-Bertrand M, Liu S, Auger N (2021). "The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis". CMAJ. 193 (16): E540–E548. doi:10.1503/cmaj.202604. PMC 8084555. PMID 33741725.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ a b "Coronavirus Disease 2019 (COVID-19)". Centers for Disease Control and Prevention. 11 February 2020. Retrieved 19 March 2020.
  3. ^ Wang H, Li N, Sun C, Guo X, Su W, Song Q; et al. (2022). "The association between pregnancy and COVID-19: A systematic review and meta-analysis". Am J Emerg Med. 56: 188–195. doi:10.1016/j.ajem.2022.03.060. PMC 8986277. PMID 35413655.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ "Update to living systematic review on covid-19 in pregnancy". BMJ. 377: o1205. 2022-05-30. doi:10.1136/bmj.o1205. ISSN 1756-1833. PMID 35636775.
  5. ^ Allotey, John; Fernandez, Silvia; Bonet, Mercedes; Stallings, Elena; Yap, Magnus; Kew, Tania; Zhou, Dengyi; Coomar, Dyuti; Sheikh, Jameela; Lawson, Heidi; Ansari, Kehkashan; Attarde, Shruti; Littmoden, Megan; Banjoko, Adeolu; Barry, Kathryn (2020-09-01). "Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis". BMJ. 370: m3320. doi:10.1136/bmj.m3320. ISSN 1756-1833. PMC 7459193. PMID 32873575.
  6. ^ a b c d Smith, Emily R.; Oakley, Erin; Grandner, Gargi Wable; Ferguson, Kacey; Farooq, Fouzia; Afshar, Yalda; Ahlberg, Mia; Ahmadzia, Homa; Akelo, Victor; Aldrovandi, Grace; Barr, Beth A. Tippett; Bevilacqua, Elisa; Brandt, Justin S.; Broutet, Nathalie; Buhigas, Irene Fernández (2023-01-01). "Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis". BMJ Global Health. 8 (1): e009495. doi:10.1136/bmjgh-2022-009495. hdl:10044/1/104684. ISSN 2059-7908. PMC 9895919. PMID 36646475.
  7. ^ Guo, Zhenming; Luo, Yingchun; Bi, Yan; Liu, Liangjie; Qi, Yuan (November 2024). "Association between situs inversus and maternal SARS-CoV-2 infection at gestational age 4–6 weeks". Med. 5 (11): 1433–1441.e3. doi:10.1016/j.medj.2024.07.009. PMID 39094582.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Duan, Lian; Yin, Huamin; Liu, Jiaxin; Wang, Wenhang; Huang, Peijun; Liu, Li; Shen, Jingling; Wang, Zhendong (2024-11-09). "Maternal COVID-19 infection associated with offspring neurodevelopmental disorders". Molecular Psychiatry: 1–11. doi:10.1038/s41380-024-02822-z. ISSN 1476-5578. PMID 39521839.
  9. ^ Şahan, Yasemin Özdemir; Sakcak, Bedri; Göncü Ayhan, Şule; Tanaçan, Atakan; Kibar Gül, Ayşe Esin; Şahin, Dilek; İlker Çetin, İbrahim (2024-01-17). "The influence of maternal COVID-19 on cardiac functions: From fetal life to infancy". Echocardiography. 41 (1): e15736. doi:10.1111/echo.15736. ISSN 0742-2822. PMID 38284669.
  10. ^ a b Hill, Rachel A.; Gibbons, Andrew; Han, Uni; Suwakulsiri, Wittaya; Taseska, Angela; Hammet, Fleur; Southey, Melissa; Malhotra, Atul; Fahey, Michael; Palmer, Kirsten R.; Hunt, Rod W.; Lim, Izaak; Newman-Morris, Vesna; Sundram, Suresh (February 2023). "Maternal SARS-CoV-2 exposure alters infant DNA methylation". Brain, Behavior, & Immunity - Health. 27: 100572. doi:10.1016/j.bbih.2022.100572. ISSN 2666-3546. PMC 9758784. PMID 36570792.
  11. ^ Yates, Emma F.; Mulkey, Sarah B. (July 2024). "Viral infections in pregnancy and impact on offspring neurodevelopment: mechanisms and lessons learned". Pediatric Research. 96 (1): 64–72. doi:10.1038/s41390-024-03145-z. ISSN 0031-3998. PMC 11257821. PMID 38509227.
  12. ^ Patanè, Luisa; Morotti, Denise; Giunta, Monica Rosaria; Sigismondi, Cristina; Piccoli, Maria Giovanna; Frigerio, Luigi; Mangili, Giovanna; Arosio, Marco; Cornolti, Giorgio (August 2020). "Vertical transmission of coronavirus disease 2019: severe acute respiratory syndrome coronavirus 2 RNA on the fetal side of the placenta in pregnancies with coronavirus disease 2019–positive mothers and neonates at birth". American Journal of Obstetrics & Gynecology MFM. 2 (3): 100145. doi:10.1016/j.ajogmf.2020.100145. ISSN 2589-9333. PMC 7233206. PMID 32427221.
  13. ^ Sisman, Julide; Jaleel, Mambarambath A.; Moreno, Wilmer; Rajaram, Veena; Collins, Rebecca R.J.; Savani, Rashmin C.; Rakheja, Dinesh; Evans, Amanda S. (2020-07-10). "Intrauterine Transmission of SARS-COV-2 Infection in a Preterm Infant". Pediatric Infectious Disease Journal. 39 (9): e265–e267. doi:10.1097/inf.0000000000002815. ISSN 0891-3668. PMID 32658097.
  14. ^ Sisman, Julide; Jaleel, Mambarambath A.; Moreno, Wilmer; Rajaram, Veena; Collins, Rebecca R.J.; Savani, Rashmin C.; Rakheja, Dinesh; Evans, Amanda S. (September 2020). "Intrauterine Transmission of SARS-COV-2 Infection in a Preterm Infant". Pediatric Infectious Disease Journal. 39 (9): e265–e267. doi:10.1097/INF.0000000000002815. ISSN 0891-3668. PMID 32658097.
  15. ^ Musa, Salihu S.; Bello, Umar M.; Zhao, Shi; Abdullahi, Zainab U.; Lawan, Muhammad A.; He, Daihai (2021-09-20). "Vertical Transmission of SARS-CoV-2: A Systematic Review of Systematic Reviews". Viruses. 13 (9): 1877. doi:10.3390/v13091877. ISSN 1999-4915. PMC 8471858. PMID 34578458.
  16. ^ a b c Yates, Emma F.; Mulkey, Sarah B. (2024-03-20). "Viral infections in pregnancy and impact on offspring neurodevelopment: mechanisms and lessons learned". Pediatric Research. 96 (1): 64–72. doi:10.1038/s41390-024-03145-z. ISSN 0031-3998. PMC 11257821. PMID 38509227.
  17. ^ Paniz-Mondolfi, Alberto; Bryce, Clare; Grimes, Zachary; Gordon, Ronald E.; Reidy, Jason; Lednicky, John; Sordillo, Emilia Mia; Fowkes, Mary (2020-06-09). "Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)". Journal of Medical Virology. 92 (7): 699–702. doi:10.1002/jmv.25915. ISSN 0146-6615. PMC 7264598. PMID 32314810.
  18. ^ a b Iadecola, Costantino; Anrather, Josef; Kamel, Hooman (October 2020). "Effects of COVID-19 on the Nervous System". Cell. 183 (1): 16–27.e1. doi:10.1016/j.cell.2020.08.028. ISSN 0092-8674. PMC 7437501. PMID 32882182.
  19. ^ Esposito, Giuseppe; Pesce, Marcella; Seguella, Luisa; Sanseverino, Walter; Lu, Jie; Sarnelli, Giovanni (July 2020). "Can the enteric nervous system be an alternative entrance door in SARS-CoV2 neuroinvasion?". Brain, Behavior, and Immunity. 87: 93–94. doi:10.1016/j.bbi.2020.04.060. ISSN 0889-1591. PMC 7179488. PMID 32335192.
  20. ^ "Q&A on COVID-19, pregnancy, childbirth and breastfeeding". www.who.int. Retrieved 6 April 2020.
  21. ^ Michael P Rimmer, Jhia J Teh, Scott C Mackenzie, Bassel H Al Wattar, The risk of miscarriage following COVID-19 vaccination: a systematic review and meta-analysis, Human Reproduction, 2023 https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/dead036/7043098?login=false
  22. ^ a b c d e f Badell, Martina L.; Dude, Carolynn M.; Rasmussen, Sonja A.; Jamieson, Denise J. (2022-08-10). "Covid-19 vaccination in pregnancy". BMJ. 378: e069741. doi:10.1136/bmj-2021-069741. ISSN 1756-1833. PMC 9363819. PMID 35948352.
  23. ^ a b Nana, Melanie; Hodson, Kenneth; Lucas, Nuala; Camporota, Luigi; Knight, Marian; Nelson-Piercy, Cathy (2022-04-26). "Diagnosis and management of covid-19 in pregnancy". BMJ. 377: e069739. doi:10.1136/bmj-2021-069739. ISSN 1756-1833. PMID 35473709.
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