COVID-19 and Pregnancy

COVID-19 and Pregnancy

By: Amik Sodhi, MD; Dipen Kadaria, MD; Jorge Trabanco, MD; Zachary Burden, MD; and Mariam Louis, MD
Women’s Lung Health Network
Published: April 30, 2021

Is COVID-19 more severe in pregnancy?

Yes, probably so. In an analysis of approximately 400,000 women aged 15-44 years with symptomatic COVID-19,¹ intensive care unit stay, use of invasive ventilation, use of extracorporeal membrane oxygenation, and death were more likely in pregnant women than in nonpregnant women. Another study evaluated more than 400,000 pregnant patients with and without COVID-19.² Although overall in-hospital mortality was low, pregnant patients with COVID-19 were 26 times more likely to die compared with those without COVID-19. Need for intensive care monitoring, mechanical ventilation requirement, venous thromboembolic disease, and thrombotic events were also more common in pregnant patients. Among women with COVID-19 who gave birth, factors identified that increased odds of mechanical ventilation use or in-hospital death were age, morbid obesity, diabetes, kidney disease, eclampsia, and thrombotic events.

Does COVID-19 have any effects on the fetus/neonate?

Adverse effects: Yes, probably so. In a systematic review and meta-analysis of 77 studies, COVID-19 during pregnancy was associated with higher likelihood of preterm birth, and neonates born to mothers with COVID-19 had an increased risk for NICU admission.³ The frequency of fetal vascular malperfusion noted on placental pathology, indicative of thrombi in fetal vessels, was increased in women with COVID-19 versus those without.⁴ These pathological changes in the placenta have previously been associated with fetal demise, fetal growth restriction, and oligohydramnios.

Currently, it is unclear whether these pathological findings are universal in patients with COVID-19 or if they develop in a certain subgroup. Adverse fetal outcomes in pregnant women with COVID-19 appear to be increased with a lower age of gestation at diagnosis, lower birthweight, or if the mother required ventilatory or oxygen support.⁵

Protective effects: Possibly, but not enough data to say so definitively. Neonatal protection from infections depends on their innate immune responses and maternally-derived antibodies that are transplacentally acquired. Antibodies (IgG and IgM) to the receptor binding domain of the SARS-CoV-2 spike were measured in dyads of pregnant women and neonates at a single center.⁶ Higher neonatal IgG levels were noted with higher maternal IgG (r = 0.886, P < .001). Placental transfer ratios more than 1 were observed for asymptomatic and all severity levels of symptomatic maternal COVID-19. The ability of maternal IgG antibodies to be efficiently passed to the neonate can potentially protect the neonate and inform decisions regarding vaccination strategies in women, including timing of vaccination (increasing time between onset of maternal infection and delivery was associated with higher transfer ratios).

Should your pregnant patient get the COVID-19 vaccine?

The American College of Obstetricians and Gynecologists (ACOG) issued a statement in January 2021 stating that COVID-19 vaccines should not be withheld from pregnant individuals,⁷ given that COVID-19 disease during pregnancy increases the risk of in-hospital death, venous thromboembolism, and preeclampsia.²

Although pregnant women were excluded from initial trials of COVID-19 vaccination, a subsequent study demonstrated that pregnant women develop robust antibody titers in response to mRNA vaccination.⁸ This response is similar to nonpregnant women and indirectly suggests that pregnant women vaccinated with an mRNA vaccine have similar immunity to nonpregnant women. Furthermore, COVID-19 mRNA vaccination causes antibody-mediated immune transfer to neonates via the placenta, indicating that there may be neonatal protection from SARS-CoV-2 infection.⁸

Given that mRNA COVID-19 vaccination produces robust antibody titers against SARS-CoV-2, it is reasonable to recommend mRNA COVID-19 vaccination to pregnant women to potentially decrease these complications. However, the decision to get vaccinated is solely at the patient’s discretion.

What are the effects of the COVID-19 vaccine on fertility?

Concern of the COVID-19 vaccine causing problems in female fertility arose after a theory stating that the vaccine could potentially cross-react with protein syncytin-1, an envelope protein originating from a human endogenous retrovirus and that is crucial in forming the human placenta. There was concern that this could lead to infertility in women. However, researchers have shown that while the coronavirus’s spike protein and syncytin-1 share small stretches of the same genetic code, it not enough to make them a match.⁹ Furthermore, during the Pfizer vaccine trial, pregnant patients were excluded initially using pregnancy tests, and throughout the study, 12 patients became pregnant in the vaccine group and 11 in the placebo group without issues.

Currently, ACOG, the American Society for Reproductive Medicine, and the Society for Maternal-Fetal Medicine have recommended the vaccine for pregnant women and assure patients that the vaccine will not cause infertility.¹⁰ Based on the current information and expert opinion, the vaccine does not appear to cause infertility and is safe for use in both men and women,¹¹ and active recruitment in three clinical trials to further assess this are currently underway.

References

1. Zambrano LD, Ellington S, Strid P, et al; CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team. Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(44):1641-1647. PMID: 33151921. doi: 10.15585/mmwr.mm6944e3
2. Jering KS, Claggett BL, Cunningham JW, et al. Clinical characteristics and outcomes of hospitalized women giving birth with and without COVID-19. JAMA Intern Med. 2021:e209241. Preprint. Posted online January 15, 2021. PMID: 33449067. doi: 10.1001/jamainternmed.2020.9241
3. Allotey J, Stallings E, Bonet M, et al; for PregCOV-19 Living Systematic Review Consortium. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020;370:m3320. PMID: 32873575. doi: 10.1136/bmj.m3320
4. Prabhu M, Cagino K, Matthews KC, et al. Pregnancy and postpartum outcomes in a universally tested population for SARS-CoV-2 in New York City: a prospective cohort study. BJOG. 2020;127(12):1548-1556. Preprint. Published online August 13, 2020. PMID: 32633022. doi: 10.1111/1471-0528.16403
5. Di Mascio D, Sen C, Saccone G, et al. Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19. J Perinat Med. 2020;48(9):950-958. PMID: 32975205. doi: 10.1515/jpm-2020-0355
6. Flannery DD, Gouma S, Dhudasia MB, et al. Assessment of maternal and neonatal cord blood SARS-CoV-2 antibodies and placental transfer ratios. JAMA Pediatr. 2021:e210038. Preprint. Published online January 29, 2021. PMID: 33512440. doi: 10.1001/jamapediatrics.2021.0038
7. The American College of Obstetricians and Gynecologists. ACOG and SMFM joint statement on WHO recommendations regarding COVID-19 vaccines and pregnant individuals. January 27, 2021. https://www.acog.org/news/news-releases/2021/01/acog-and-smfm-joint-statement-on-who-recommendations-regarding-covid-19-vaccines-and-pregnant-individuals
8. Gray KJ, Bordt EA, Atyeo C, et al. COVID-19 vaccine response in pregnant and lactating women: a cohort study. Am J Obstet Gynecol. 2021;S0002-9378(21)00187-3. PMID: 33775692; PMCID: PMC7997025. doi: 10.1016/j.ajog.2021.03.023
9. Kloc M, Uosef A, Kubiak JZ, et al. Exaptation of retroviral syncytin for development of syncytialized placenta, its limited homology to the SARS-CoV-2 spike protein and arguments against disturbing narrative in the context of COVID-19 vaccination. Biology (Basel). 2021;10(3):238. PMID: 33808658. doi: 10.3390/biology10030238
10. Iacobucci G. Covid-19: no evidence that vaccines can affect fertility, says new guidance. BMJ. 2021;372:n509. doi:10.1136/bmj.n509
11. American Society for Reproductive Medicine. ASRM, ACOG and SMFM issue joint statement: medical experts continue to assert that COVID vaccines do not impact fertility. February 5, 2021. https://www.asrm.org/news-and-publications/news-and-research/press-releases-and-bulletins/asrm-smfm-acog-issue-joint-statement-medical-experts-continue-to-assert-that-covid-vaccines-do-not-impact-fertility/

Amik Sodhi, MD

• Associate Professor of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Tennessee Health Science Center

Dipen Kadaria, MD

• Associate Professor of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Tennessee Health Science Center

Jorge Trabanco, MD

• Fellow, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, Jacksonville

Zachary Burden, MD

• Fellow, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, Jacksonville

Mariam Louis, MD

• Associate Professor, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, Jacksonville

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