**3. What we know about COVID-19 during pregnancy and the prognosis of the fetus and offspring**

At the beginning of the pandemic, the clinical manifestations of COVID-19 in pregnant women and babies were unknown. Some studies concluded that the evolution of SARS-CoV-2 infection in pregnant and nonpregnant women was similar [6, 34]. A case–control study compared the clinical evolution of COVID-19 between pregnant women with and without COVID-19 and observed that pregnant women with mild symptoms of COVID-19 have a similar evolution to those without the disease. However, pregnant patients with severe or critical illness have worse results. The risk factors for a worse maternal and neonatal outcome include black and Hispanic race, advanced maternal age, obesity, comorbidities (diabetes mellitus and chronic hypertension), and admission to the COVID-19-related antepartum [35].

Immune responses in pregnancy induce that pregnancy is a risk factor for SARS-CoV-2 infection. In both normal and COVID-19-infected pregnancies, maternal immune responses occur as a result of decreased lymphocytes, inhibitory natural killer cell receptor activation such as NKG2A, and increased inflammatory cytokines (interferon-ɣ, interleukin (IL)-2, IL-6, IL-7, IL-10, and tumor necrosis factor-α) [36, 37]. In addition, the angiotensin-converting enzyme 2 is the receptor for SARS-CoV-2 and is widely expressed in the female reproductive system (ovary, uterus, vagina, and placenta) and fetal tissues; therefore, vertical transmission of COVID-19 is possible [38, 39].

The fetuses of mothers infected with SARS-CoV-2 may be exposed to an intense inflammatory response, which can induce placental or fetal damage. Nonspecific anatomopathological changes were observed in SARS-CoV-2 infected placentas, and the most common finding was poor placental perfusion on the maternal side due to maternal hypoxia secondary to severe pulmonary infection by COVID-19.

Both maternal immune response and poor placental perfusion can result in abortions, pre-eclampsia, prematurity, and IUGR [37, 40].

A study that evaluated the fetal inflammatory response in newborns of mothers infected with COVID-19 in the third trimester observed an increase in IL-6 in the fetuses, which may determine adverse sequelae of neurological development, including autism, psychosis, and long-term sensorineural deficits. However, longitudinal studies are needed to validate these associations (**Table 1**) [37, 41].

Only one study confirmed the vertical intrauterine transmission. In the case report described by Vivanti et al., the pregnant woman was in her last trimester of pregnancy (35 weeks) when she developed symptoms and was diagnosed with COVID-19. Cesarean delivery was indicated because of fetal distress. The conceptus was resuscitated at birth and transferred in invasive mechanical ventilation to the ICU. The virus was investigated and detected by RT-PCR from the amniotic fluid, placental tissue, bronchoalveolar lavage fluid, blood, and nasopharyngeal and anal swabs. The conceptus evolved with neurological manifestations similar to those described in adult patients with COVID-19 [11].

A review study evaluated 108 pregnant women confirmed with COVID-19 and found that 86 had pregnancy resolution. Of the newborns, 75 were tested for SARS-CoV-2 using RT-PCR, and only one was positive (1.3%). The test was collected at 36 h of life. The patient presented a good clinical evolution with reports of lymphopenia and increased liver enzymes in laboratory tests. The average gestational age of the 86 pregnancies evaluated was 36 weeks and 1 day. One baby died at birth (1.1%), and one pregnancy resulted in intrauterine death (1.1%). In both cases, the mothers had severe COVID-19. Seven babies (8.1%) required admission to the neonatal ICU [42].

A study of nine case series and two case reports evaluated 65 mothers confirmed for COVID-19 and 57 newborns. The report revealed that 31% of cases had fetal distress, and 38% of pregnant women had a premature birth. Neonatal complications were breathing difficulties or pneumonia (18%), low birth weight (13%), skin rash (3%), disseminated intravascular coagulation (3%), asphyxia (2%), and perinatal death (3%). Twenty-seven newborns underwent RT-PCR for SARS-CoV-2 by nasopharyngeal swab. Of them, four were positive: one newborn was healthy, and three had pneumonia and positive results on nasopharynx and anal swabs on days 2 and 4 of life. The question remains whether some of the maternal and neonatal complications reported are due to the virus and not iatrogenic, for example, the indication for cesarean delivery determining premature birth [43].

The infection by the SARS-CoV-2 virus presents neurological manifestations, which can be a consequence of cardiorespiratory failure and metabolic abnormalities triggered by the infection, direct invasion of the virus, or an autoimmune response to the virus. Among the neurological symptoms observed were headache, ageusia, anosmia, dizziness, myalgia/myositis, and stroke [44, 45]. The effects of this neurotropism of the virus should be investigated in children, especially in newborns whose mothers were infected during pregnancy, since its consequences on children's neurological development are unknown. In addition, the effects of infection according to the trimester of pregnancy are unknown, leaving doubt about the prognosis of children of mothers infected in the first trimester, in relation to other periods of pregnancy (**Table 2**).

International Health Security, also called "global health security" or "public health security", has as its main objective to maintain humanity's well-being through prevention. Its focus is not only on diseases (infectious, chronic), it also encompasses social determinants of health, bioterrorism, climate change, cybersecurity in health and other situations.

*Perinatal COVID-19 Pandemic: Short- and Long-Term Impacts on the Health of Offspring DOI: http://dx.doi.org/10.5772/intechopen.99022*


### **Table 2.**

*Studies that evaluated the clinical manifestations in newborns born to mothers confirmed with COVID-19.*

COVID-19 is a threat to international health security, as it has repercussions in all aspects of human health, physical, social and mental well-being, as the disease causes death, sequelae, compromised mental health and social of individuals.

In children, in addition to the impact of the absence of face-to-face classes in schools and social interaction, the impact of intrauterine SARS-CoV-2 infection on their neurological and body development is still uncertain. Being an item of extreme importance to International Health Security.

### **4. Conclusion**

It is vital to monitor the growth and proper development of children exposed to COVID-19 during pregnancy since whether or not vertical transmission occurs is still uncertain, and if confirmed, fetal prognosis should be improved through diagnosis to determine early consequences. Several viral infections during pregnancy can compromise the health of the fetuses in the short, medium, and long term.

### **Conflict of interest**

The authors declare no conflict of interest.
