Molecular regulation of lung maturation in near-term fetal sheep by maternal daily vitamin C treatment in late gestation

Background In the fetus, the appropriate balance of prooxidants and antioxidants is essential to negate the detrimental effects of oxidative stress on lung maturation. Antioxidants improve respiratory function in postnatal life and adulthood. However, the outcomes and biological mechanisms of antioxidant action in the fetal lung are unknown. Methods We investigated the effect of maternal daily vitamin C treatment (200 mg/kg, intravenously) for a month in late gestation (105–138 days gestation, term ~145 days) on molecular regulation of fetal lung maturation in sheep. Expression of genes and proteins regulating lung development was quantified in fetal lung tissue. The number of surfactant-producing cells was determined by immunohistochemistry. Results Maternal vitamin C treatment increased fetal lung gene expression of the antioxidant enzyme SOD-1, hypoxia signaling genes (HIF-2α, HIF-3α, ADM, and EGLN-3), genes regulating sodium movement (SCNN1-A, SCNN1-B, ATP1-A1, and ATP1-B1), surfactant maturation (SFTP-B and ABCA3), and airway remodeling (ELN). There was no effect of maternal vitamin C treatment on the expression of protein markers evaluated or on the number of surfactant protein-producing cells in fetal lung tissue. Conclusions Maternal vitamin C treatment in the last third of pregnancy in sheep acts at the molecular level to increase the expression of genes that are important for fetal lung maturation in a healthy pregnancy. Impact Maternal daily vitamin C treatment for a month in late gestation in sheep increases the expression of gene-regulating pathways that are essential for normal fetal lung development. Following late gestation vitamin C exposure in a healthy pregnancy, an increase in lung gene but not protein expression may act as a mechanism to aid in the preparation for exposure to the air-breathing environment after birth. In the future, the availability/development of compounds with greater antioxidant properties than vitamin C or more specific targets at the site of oxidative stress in vivo may translate clinically to improve respiratory outcomes in complicated pregnancies at birth.

Anaplastic astrocytoma during pregnancy: the importance of an effective multidisciplinary approach

A 34-year-old pregnant woman at 28 gestational weeks was diagnosed with a brain tumor after experiencing a generalised seizure. After completion of antenatal fetal lung maturation, she underwent an osteoplastic craniotomy parietal on the left side and a microsurgical partial tumor resection under general anaesthesia. With a histology of a diffuse astrocytoma and the postoperative stable amount of residual tumor on follow-up imaging, the pregnancy proceeded until 37 gestational weeks. A healthy baby boy was delivered by elective caesarean section. An awake craniotomy for removal of the residual tumor was planned two weeks later, followed by adjuvant treatment (combined radio-/chemotherapy). A multidisciplinary approach, combined with appropriate timing and a transparent and empathic communication, was able to create the most effective tailored management and optimise maternal and neonatal outcomes.

Outcomes of pregnancies in women with extremely high ratio of sFlt-1 / PlGF: a series of clinical cases

Preeclampsia as one of the manifestations of placental dysfunction associated with dysregulation of pro- and antiangiogenic factors. During normal pregnancy, the concentration of antiangiogenic factor sFlt-1 remains low, which allows accurate transmission of signals induced by proangiogenic factors VEGF and PlGF. This balance is crucial to maintain physiological vasodilation. Under hypoperfusion, the placenta increases the synthesis of sFlt-1, trying to increase maternal pressure and increase placental perfusion.The objective: to study the clinical outcomes of pregnancies in a group with extremely high ratios of sFlt-1 and PlGF.Materials and methods. The results of determining the levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sfLT-1), which were performed during 2017-2020 in the serum of 128 pregnant women at 18–39 weeks, were analyzed.Results. The mean age of pregnant women was 28,4±4 years. The average gestational age during the study was 26±5 weeks. The majority of pregnant women had signs of IUGR (62,5%) and/or preeclampsia (50%) during the study. The average level of the sFlt/PIGF ratio was 1747 pg/ml. In 100% of cases with a digital ratio of more than 850, signs of an obstetric angiogenic catastrophe that required immediate delivery developed during the nearest future. The average time from analysis to delivery was 10 days. In 50% of pregnant women, urgent delivery was required within 48 hours after analysis. Favorable neonatal results were observed in 37,5% of women.Conclusion. We found a tendency for worsening perinatal outcomes in women with extremely high sFlt-1/PlGF ratios after reaching 850. Careful monitoring of the pregnant woman and consideration of need for prophylactic administration of corticosteroids to accelerate fetal lung maturation in this group is rational.

SARS-CoV-2: do corticosteroids for fetal lung maturation worsen maternal or fetal outcomes?

Immune system changes during pregnancy could make pregnant women more susceptible to SARS-Cov-2 infection. The use of corticosteroids within obstetrics has been shown to reduce the risks of respiratory distress syndrome, intraventricular haemorrhage, necrotizing enterocolitis and neonatal death in the baby associated with premature delivery. During the COVID-19 pandemic, corticosteroids have been trialled as a treatment to dampen the ‘cytokine storm’ and associated inflammatory processes. Corticosteroids have long been known to have immunosuppressive effects that could hinder the body's ability to mount a defence against COVID-19 and thereby delaying viral clearance. In this clinical case studies, antenatal steroids for fetal lung maturation appear to be of benefit and did not result in a deterioration of maternal disease. Our clinical case studies support the current recommendations from the Royal College of Obstetricians and Gynaecologists ie corticosteroids for fetal lung maturation is appropriate in patients who are suspected or have confirmed SARS-CoV-2 infection.

Efficacy and Safety of Corticosteroids’ Administration for Pulmonary Immaturity in Anticipated Preterm Delivery

: Preterm delivery represents the major cause of neonatal morbidity and mortality. Respiratory morbidity is the primary cause of early neonatal mortality and disability. The administration of antenatal corticosteroids, in cases of imminent preterm delivery, can enhance fetal lung maturation and reduce the incidence of respiratory distress syndrome, leading to improved neonatal outcomes. Hence, for those cases, a single course of antenatal corticosteroids from 24 up to 34 gestational weeks should be offered. Betamethasone and dexamethasone are the most widely used drugs, with similar effectiveness and a recommended dosage of 24mg in divided doses, over a 24-hour period. However, there is an ongoing debate regarding the gestational age of administration. Some obstetric societies recommend their administration even at 22 weeks of gestation. Conflicting is also their usefulness in late preterm cases (between 34 and 37 weeks) or in cases of elective cesarean delivery at term. The use of repeated courses of corticosteroids may be considered in specific cases, however, concerns on the long-term outcomes of repeated courses beyond 34 gestational weeks have been raised. The scope of this narrative review was to synthesize available evidence on efficacy and safety of corticosteroids administration during the antenatal period for pulmonary immaturity in cases of anticipated preterm delivery.