Inflammation and Immune Reactions in the Fetus as a Response to COVID-19 in the Mother.

Background: Contracting COVID-19 during pregnancy can harm both the mother and the unborn child. Pregnant women are highly likely to develop respiratory viral infection complications with critical conditions caused by physiological changes in the immune and cardiopulmonary systems. Asymptomatic COVID-19 in pregnant women may be accompanied by fetal inflammatory response syndrome, which has adverse consequences for the newborn's life and health. Purpose: To conduct an inflammatory response assessment of the fetus due to the effects of COVID-19 on the mother during pregnancy by determining pro-inflammatory cytokines, cell markers, T regulatory cells, T cell response, evaluation of cardiac function, and thymus size. Materials and methods: A prospective study included pregnant women (n = 92). The main group consisted of 62 pregnant women with COVID-19 infection: subgroup 1-SARS-CoV-2 PCR-positive pregnant women 4-6 weeks before delivery (n = 30); subgroup 2-SARS-CoV-2 PCR-positive earlier during pregnancy (n = 32). The control group consisted of 30 healthy pregnant women. In all pregnant women, the levels of circulating cytokines and chemokines (IL-1α, IL-6, IL-8, IL-10, GM-CSF, TNF-α, IFN-γ, MIP-1ß, and CXCL-10) were determined in the peripheral blood and after delivery in the umbilical cord blood, and an analysis was performed of the cell markers on dendritic cells, quantitative and functional characteristics of T regulatory cells, and specific T cell responses. The levels of thyroxine and thyroid-stimulating hormone were determined in the newborns of the studied groups, and ultrasound examinations of the thymus and echocardiography of the heart were also performed. Results: The cord blood dendritic cells of newborns born to mothers who suffered from COVID-19 4-6 weeks before delivery (subgroup 1) showed a significant increase in CD80 and CD86 expression compared to the control group (p = 0.023). In the umbilical cord blood samples of children whose mothers tested positive for COVID-19 4-6 weeks before delivery (subgroup 1), the CD4+CCR7+ T cells increased with a concomitant decrease in the proportion of naive CD4+ T cells compared with the control group (p = 0.016). Significantly higher levels of pro-inflammatory cytokines and chemokines were detected in the newborns of subgroup 1 compared to the control group. In the newborns of subgroup 1, the functional activity of T regulatory cells was suppressed, compared with the newborns of the control group (p < 0.001). In all pregnant women with a severe coronavirus infection, a weak T cell response was detected in them as well as in their newborns. In newborns whose mothers suffered a coronavirus infection, a decrease in thymus size, transient hypothyroxinemia, and changes in functional parameters according to echocardiography were revealed compared with the newborns of the control group. Conclusions: Fetal inflammatory response syndrome can occur in infants whose mothers suffered from a COVID-19 infection during pregnancy and is characterized by the activation of the fetal immune system and increased production of pro-inflammatory cytokines. The disease severity in a pregnant woman does not correlate with SIRS severity in the neonatal period. It can vary from minimal laboratory parameter changes to the development of complications in the organs and systems of the fetus and newborn.

Current perspective and scope of fetal therapy: part 1.

Fetal therapy term has been described for any therapeutic intervention either invasive or noninvasive for the purpose of correcting or treating any fetal malformation or condition. Fetal therapy is a rapidly evolving specialty and has gained pace in last two decades and now fetal intervention is being tried in many malformations with rate of success varying with the type of different fetal conditions. The advances in imaging techniques have allowed fetal medicine persons to make earlier and accurate diagnosis of numerous fetal anomalies. Still many fetal anomalies are managed postnatally because the fetal outcomes have not changed significantly with the use of fetal therapy and this approach avoids unnecessary maternal risk secondary to inutero intervention. The short-term maternal risk associated with fetal surgery includes preterm labor, premature rupture of membranes, uterine wall bleeding, chorioamniotic separation, placental abruption, chorioamnionitis, and anesthesia risk. Whereas, maternal long-term complications include risk of infertility, uterine rupture, and need for cesarean section in future pregnancies. The decision for invasive fetal therapy should be taken after discussion with parents about the various aspects like postnatal fetal outcome without fetal intervention, possible outcome if the fetal intervention is done, available postnatal intervention for the fetal condition, and possible short-term and long-term maternal complications. The center where fetal intervention is done should have facility of multi-disciplinary team to manage both maternal and fetal complications. The major issues in the development of fetal surgery include selection of patient for intervention, crafting effective fetal surgical skills, requirement of regular fetal and uterine monitoring, effective tocolysis, and minimizing fetal and maternal fetal risks. This review will cover the surgical or invasive aspect of fetal therapy with available evidence and will highlight the progress made in the management of fetal malformations in last two decades.

Current perspective and scope of fetal therapy: part 2.

Fetal therapy has been defined as any therapeutic intervention either invasive or noninvasive for correcting or treating any fetal malformation or condition. Invasive fetal therapy have its own set of maternal and fetal complications and invasive approach is not feasible in many of fetal conditions that are candidate for fetal therapy. Many such fetal conditions have been treated successfully by medical or noninvasive management. In medical fetal therapy, mothers are treated with medications which are transferred to fetus through placenta and exert positive effect on the fetus, thus avoiding complications that are seen secondary to invasive fetal therapy. The fetal conditions that have been managed with medical therapy includes fetal and neonatal alloimmune thrombocytopenia, neural tube defect, congenital adrenal hyperplasia, perinatal infections, respiratory distress syndrome, inborn error of metabolism, and congenital cystic adenomatoid malformation. This review will cover the medical or noninvasive aspect of fetal therapy and will highlight the progress made in the management of these fetal conditions.

3D-printing in preoperative planning in neonates with complex congenital heart defects.

The application of the 3D printing approach in medicine is currently becoming increasingly popular. The management of fetuses and newborns with congenital heart defects is often difficult, primarily due to the complexity of the anatomy. Here we report a newborn with a complex congenital malformation (absent pulmonary valve syndrome associated with tetralogy of Fallot), which could be clinically interpreted in different ways. 3D printing allowed to elucidate the exact anatomy more precisely and direct the cardiosurgeon to a definitive treatment.