COVID-19 infection in

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

is associated with several

pregnancy complications Complications of pregnancy are health problems that are related to or arise during pregnancy. Complications that occur primarily during childbirth are termed obstetric labor complications, and problems that occur primarily after childbirth are term ...

. However, pregnancy does not appear to increase the susceptibility of becoming infected by COVID-19. Recommendations for the prevention of COVID-19 include the same measures as non-pregnant people.

Effect of COVID-19 in pregnancy

According to a

systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on ...

and meta-analysis in 2021, COVID-19 is associated with

stillbirth Stillbirth is typically defined as fetus, fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without vital signs, signs of life. A stillbirth can often result in the feeling of guilt (emotio ...

pre-eclampsia Pre-eclampsia is a multi-system disorder specific to pregnancy, characterized by the new onset of hypertension, high blood pressure and often a significant amount of proteinuria, protein in the urine or by the new onset of high blood pressure a ...

and

preterm birth Preterm birth, also known as premature birth, is the Childbirth, birth of a baby at fewer than 37 weeks Gestational age (obstetrics), gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 ...

. According to the same review, compared with mild COVID-19, severe COVID-19 is strongly associated with preeclampsia, preterm birth,

gestational diabetes Gestational diabetes is a condition in which a woman without diabetes develops hyperglycemia, high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms. Obesity increases the rate of pre-eclampsia, cesarea ...

and low birth weight. 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. A systematic review update in 2022 demonstrated that pregnant women are at increased risk of severe COVID-19. It also found that

risk factor In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...

s for severe COVID-19 in pregnant people included high body mass index, being of an older age, being of non-white

ethnic origin An ethnicity or ethnic group is a group of people with shared attributes, which they collectively believe to have, and long-term endogamy. Ethnicities share attributes like language, culture, common sets of ancestry, traditions, society, rel ...

, having pre-existing comorbidities, having

or gestational diabetes. 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. 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. This study used the first large set of pregnancy cohort data from sub-Saharan Africa. A marked increase in cases of

situs inversus ''Situs inversus'' (also called ''situs transversus'' or ''oppositus'') is a Congenital disorder, congenital condition in which the major Organ (anatomy), visceral organs are reversed or mirror image, mirrored from their normal positions. The norm ...

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.

Effect of SARS-CoV-2 on Fetal Neurodevelopment

Maternal infection increases the chance of

neurodevelopmental disorders Neurodevelopmental disorders are a group of mental conditions negatively affecting the development of the nervous system, which includes the human brain, brain and spinal cord. According to the American Psychiatric Association Diagnostic and Sta ...

. The underlying mechanisms that cause this have not yet been elucidated. A 2024 study found impaired cardiac function in babies whose mothers contracted COVID in the second trimester. In two systematic reviews 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, 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. However, in a systematic review of systematic reviews, it is sought as a rare event. Host-virus interactions The pro-inflammatory state could disrupt the placental development, which, in turn, results in preterm birth, preeclampsia, and restricted intrauterine growth.

The Neurodevelopmental invaded by SARS-CoV-2

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 Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is compo ...

(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. 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. 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.

DNA methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter (genetics), promoter, DNA methylati ...

. Viral infection could alter DNA methylation patterns in genes involved with neurodevelopment. 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. 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. Retrograde axonal transport. The gut neurons might have transported the viruses into the nervous system.

Recommendations

Prevention

The

World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...

(WHO) and

Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...

(CDC) of the United States advises pregnant women to do the same things as the general public to avoid infection, such as wearing a mask where it is not possible to keep sufficient physical distance from others; covering cough, avoid interacting with sick people, cleaning hands with soap and water or

sanitizer A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than s ...

. Vaccination against COVID-19 was not associated with an increase in miscarriage or reduction in live birth. Meta-analysis has not identified any pregnancy-specific safety concerns with vaccines. The data overwhelming support maternal vaccination as being effective at reducing the risk for infection and severe illness. 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. 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. The

Royal College of Obstetricians and Gynaecologists The Royal College of Obstetricians and Gynaecologists (RCOG) is a professional association based in London, United Kingdom. Its members, including people with and without medical degrees, work in the field of obstetrics and gynaecology, that is ...

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 The American College of Obstetricians and Gynecologists (ACOG) is a professional association of physicians specializing in obstetrics and gynecology in the United States. Several Latin American countries are also represented within Districts of ...

and Society for Maternal-Fetal Medicine encourage pregnant women to get COVID-19 vaccines. The Federation of Obstetric and Gynaecological Societies of India recommend vaccination, though it is not currently recommended by the Government of India. More than 80 countries do not currently recommend that all pregnant and lactating women should be vaccinated. "As of today," the CDC no longer recommends healthy children and pregnant women to be vaccinated against Covid-19 as announced by the U.S. Health and Human Services (HHS) Secretary Robert F. Kennedy Jr. although there's no change in the official CDC website. The ACOG, the American College of Obstetricians and Gynecologists, responded with concerns and disappointments because the vaccine is safe to protect both the patient and her newborn, who is too young to be eligible for the vaccine. At the same time, COVID-19 could be “catastrophic” with “devastating consequences for both patients and families.” Two days later, the CDC website has complied with the (HHS) Secretary's directive by taking off the recommendation for pregnant women: "Delay vaccination until after pregnancy if vaccine is indicated."

Treatment

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

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

s should be modified to use non-fluorinated glucocorticoids and that Il-6 inhibitors and

monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a Lineage (evolution), cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Mon ...

could be used, as could specific antiviral therapies. 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 Extracorporeal membrane oxygenation (ECMO) is a form of extracorporeal life support, providing prolonged cardiac and respiratory system, respiratory support to people whose human heart, heart and human lung, lungs are unable to provide an adequa ...

References

{{Pregnancy

Health issues in pregnancy