Objective: Pregnancy is a known risk factor for severe Coronavirus disease 2019. It is important to develop safe vaccines that elicit strong maternal and fetal antibody responses. Methods: Registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the European Union Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, Springer, medRxiv, and bioRxiv) were systematically searched in June 20–22, 2021, for research articles pertaining to Covid-19 and pregnancy. Manual searches of bioRxiv and medRxiv were also conducted. Inclusion criteria were studies that focused on Covid-19 vaccination among pregnant women, while review articles and non-human studies were excluded. Infection rate, maternal antibody response, transplacental antibody transfer, and adverse events were described. Results: There were 13 observational studies with a total of 48,039 pregnant women who received mRNA vaccines. Of those, three studies investigated infection rate, six studies investigated maternal antibody response, seven studies investigated antibody transfer, three studies reported local adverse events, and five studies reported systemic adverse events. The available data suggested that the mRNA-based vaccines (Pfizer–BioNTech and Moderna) can prevent future SARS-CoV-2 infection. These vaccines did not show clear harm in pregnancy. The most commonly encountered adverse reactions were pain at the injection site, fatigue, and headache, but these were transient. Antibody responses were rapid after the first vaccine dose. After the booster, antibody responses were stronger and associated with better transplacental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and a better antibody transfer ratio. Conclusions: The SARS-CoV-2 mRNA vaccines are encouraged for pregnancy. These vaccines can be a safe option for pregnant women and their fetuses. Two vaccine doses are recommended for more robust maternal and fetal antibody responses. Longer latency is associated with higher fetal antibody responses. Further research about its long-term effect on pregnancy is needed. Systematic review registration: PROSPERO (CRD42021261684).

The use of remdesivir for pregnant patients with coronavirus disease 2019 (COVID-19) showed conflicting results in prior studies. We aimed to systematically review its efficacy and safety for this population from the existing literature. On July 26, 2021, registries (ClinicalTrials.gov) and databases (MEDLINE, ScienceDirect, Cochrane Library, JSTOR, DOAJ, and medRxiv) were systematically searched for research articles investigating remdesivir use in pregnant people with COVID-19. Clinical outcome, hospitalization duration, laboratory outcome, mortality, and adverse events were investigated. We obtained 13 observation studies with 113 pregnant people. In these studies, remdesivir improved the clinical condition of pregnant patients with COVID-19, especially those who had a better clinical status at baseline and received earlier remdesivir treatment. Most fetuses were delivered via cesarean section, primarily because of emergency causes. No vertical transmissions were noted. The most reported adverse event was transaminitis, in which 10-day remdesivir treatment yielded more incidence than the 5-day treatment. In pregnancy, the use of Remdesivir in combination with other COVID-19 treatments is inconclusive but its use should be followed with careful monitoring of adverse reactions and transaminase enzyme levels. Further studies are required to confirm its finding.

Background: Inadequate funding for vaginal delivery can be one of the barriers to reducing the maternal mortality rate. It could be therefore critical to compare the vaginal delivery cost between total hospital cost and INA-CBGs cost in national health insurance. Methods: This was a retrospective cross-sectional study conducted from October to December 2019 in Universitas Airlangga Academic Hospital. It collected data on primary diagnosis, length of stay, total hospital cost, INA-CBGs cost, and counted disparity. The data analyzed statistically using t-test independent sample (or Mann-Whitney test). Results: A total of 149 vaginal delivery claims were found, with the majority having a level II severity (79.87%) and moderate preeclampsia as a primary diagnosis (20.1%). There was a significant disparity in higher total hospital costs compared with government INA-CBGs costs (Rp. 9,238,022.09±1,265,801.88 vs 1,881,521.48±12,830.15; p<0.001). There was also an increase of LOS (p<0.001), total hospital cost (p<0.001), and cost disparity (p<0.01) in a higher severity level of vaginal delivery. Conclusion: Vaginal delivery costs in INA-CBGs scheme are underneath the actuarial value. There was also an increase in total hospital costs and a more significant disparity in the higher severity levels of vaginal delivery.

Wardhana MP, et al. Yonsei Med J. 2024 Apr;65(4):202-209. https://doi.org/10.3349/ymj.2023.0309

Objective Pregnancy is a risk factor for severe Covid-19. Looking for safe vaccines that evoke protective maternal and fetal antibody response is important. Methods We searched from registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the EU Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, and Springer) up until June 20, 2021. Articles were selected based on inclusion and exclusion criteria after duplicates were removed. Infection rate, maternal antibody response, placental antibody transfer, and adverse events were described. This systematic review was performed with quality assessment and semi-quantitative synthesis according to PRISMA guidelines. Results Twelve observational studies with a total of 40.509 pregnant women included. The mRNA based vaccines (Pfizer-BioNTech and Moderna) can prevent future SARS-CoV-2 infections (p=0.0004). Both vaccines did not affect pregnancy, delivery, and neonatal outcomes. The most commonly encountered adverse reactions are injection-site pain, fatigue, and headache but only transient. Antibody responses were rapid after the prime dose of vaccines. After booster, antibody responses were higher and associated with better placental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and better antibody transfer ratio. Conclusions The Pfizer-BioNTech and Moderna vaccines are efficacious for preventing future SARS-CoV-2 infections. These vaccines can be considered as a safe option for pregnancy and their fetus. Two doses of vaccines were recommended for more robust maternal and fetal antibody responses. Longer latency was associated with higher fetal antibody responses. Systematic Review Registration PROSPERO (CRD42021261684)

Background: Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality, yet its pathophysiology is not fully understood. Recent studies suggest that dysregulated maternal immune responses, particularly involving decidual Natural Killer (dNK) cells and immune checkpoint molecules such as B7-H3, may play a role in the pathogenesis of this heterogeneous syndrome, particularly in the development of early-onset preeclampsia (EOP). Objective: The aim of this study was to investigate the expression patterns of B7-H3 on extravillous trophoblasts (EVTs) and the abundance of dNK cells in preeclamptic versus normotensive pregnancies and to analyze the relationship between these two immune parameters. Methods: A cross-sectional study was conducted using 42 placental samples (21 preeclampsia, 21 controls). Immunohistochemistry (IHC) was performed to detect CD56 (dNK cells) and CD276 (B7-H3) expression. Expression was semi-quantitatively evaluated using the Remmele Immunoreactive Score (IRS). Statistical comparisons and correlation analyses were conducted. Results: Preeclamptic placentas exhibited significantly higher dNK cell expression (IRS 7.19 ± 2.16) and significantly lower B7-H3 expression (IRS 2.63 ± 0.90) compared to controls (p < 0.001 and p = 0.002, respectively). A positive correlation was found between B7-H3 and dNK cell expression in both groups, with a stronger correlation in normotensive pregnancies (r = 0.605; p = 0.004) and preeclampsia (r = 0.465; p = 0.034). Conclusions: The inverse expression pattern and reduction in B7-H3 expression compared to dNK cells in preeclampsia suggest a loss of immune tolerance at the maternal–fetal interface. These findings highlight the potential of B7-H3 as a biomarker and immunoregulatory target for early prediction and prevention of preeclampsia.