Preterm labor (before 34 or 37 gestational weeks) was the most common COVID-19 side effect in pregnant women [2, 4]. Preeclampsia-related neonatal mortality, preterm membrane rupture, and fetal development restriction were among the others [2, 4]. Fetal distress, neonatal asphyxia, a high rate of NICU admission, stillbirth, and neonatal death were the most common outcomes reported in fetuses and neonates .
In some research, vertical transmission of coronavirus (SARS-CoV-2) from mother to fetus has been suggested [1, 2, 4]. A newborn infant born to a woman infected with SARS-CoV-2 had higher IgM antibody and cytokine levels 2 h after birth, implying in utero viral infection because IgM antibodies cannot cross the placenta .
The virus can pass the blood–brain barrier and influence the neurological system, as evidenced by the presence of viral IgM in cerebrospinal fluid [1, 2].
In another case, the placenta of a stillborn fetus tested positive for SARS-CoV-2, and the umbilical cord connective tissue was inflamed, indicating fetal inflammatory response . In another example of SARS-CoV-2 infection in a pregnant woman, the placenta contained inflammatory infiltrates, indicating infection transfer from mothers to their fetuses .
The virus needs angiotensin-converting enzyme 2 (ACE2) and S protein protease receptors to enter the cell, and these receptors are found in developing human embryos in the early stages of development (gametes, zygotes, and 4-cell embryos) [1, 2]. As a result, the virus has the ability to penetrate fetal cells at an early stage of development and affect cell transformation and growth, a theory that tries to illustrate the mechanism of SARS-CoV-2 transmission from mother to fetus in early pregnancy [1, 2].
The human heart is one of the earliest organs to develop and begin functioning during the embryonic period. At week 7 of pregnancy, the four-chambered heart is fully formed . The failure of the endocardial cushions to fuse during the embryonic development of the heart causes an atrioventricular septal defect (AVSD) .
A meta-analysis found that when compared to mothers who did not have a viral infection at the start of pregnancy, a viral illness such as rubella and cytomegalovirus infections in early pregnancy greatly increases the chance of developing heart diseases in offspring .
The abnormal accumulation of fluid in two or more fetal compartments, such as the abdominal cavity, pleural effusion, pericardial effusion, and skin edema, is referred to as hydrops fetalis. One of the reasons for fetal hydrops is viral infection . SARS-CoV-2 infection was recently reported in two pregnant women, and their fetuses had fetal transient cutaneous edema . One of the most common causes of fetal hydrops is congenital heart abnormalities .
The absence of additional risk factors that can cause complete AVSD other than covid-19 infection at the beginning of the pregnancy led us to suggest that Covid-19 may be linked to congenital heart disease (CHD) in this particular case. The biggest risk factors for complete AVSD, according to Myoclinic medical database, are Down syndrome, rubella or other viral infections, diabetes mellitus, smoking, alcohol, and specific drugs .
As we previously indicated, the mother in question had no history of illness, was not diabetic or hypertensive, did not smoke or drink, and was not taking any medications prior to or throughout the first trimester of pregnancy. The mother was 34 years old; prior research has shown that neither pregnancy outcomes nor risk factors for fetal congenital abnormalities are affected by this age [12, 13].
One of the study’s limitations is the lack of fetal autopsy and placental histological examination, but based on the aforementioned findings and in line with recent case reports, we suggest that covid-19 infection of the mother at beginning of pregnancy might play a role in producing this rare and complicated CHD in the case that was accompanied by encephalopathy and hydrops fetalis.
The American Heart Association (AHA) mentioned in its guidelines for the diagnosis and management of fetal cardiac illness that prenatal virus exposure may be linked to positive cardiac findings when ultrasonography signs such as effusions or hydrops are present . The infant girl in our case showed hydrops fetalis, which may imply CHD caused by a viral infection. Although, hydrops may be a result of CHD .
Because polyhydramnios is highly correlated with fetal AVSD, echocardiograms should be performed when polyhydramnios is detected by ultrasound in any mother who has CHD risk factors, such as viral infection .
Numerous recent investigations illustrate that the SARS-CoV-2 virus can pass through the placenta and affect the fetus [16, 17], which is based on immunohistochemical tests and the confirmation of non-immunologic hydrops fetalis.
Finally, an editorial opinion report about two case reports that presented three neonates without any positive reverse transcriptase-polymerase chain reaction test results to any infant specimen gave the conclusion that they had been exposed to SARS-CoV-2 in utero from their mothers based on elevated IgM and IgG antibody values in the neonates’ postnatal blood and recommended further investigations .
Although, all case reports discussed the effects of covid-19 on fetuses in the second and third trimesters, results are in line with our suggestion that SARS-CoV-2 can affect fetuses. Further observational studies should be done to investigate covid-19 effect on mothers and fetuses at early pregnancy.
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