Manggala Pasca Wardhana

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.

HIGHLIGHTS ABSTRACT Objective: This study aimed to evaluate the effectiveness of the "TAMENG" flipchart as an educational tool to improve knowledge about anemia prevention among pregnant women in Sumber, Kabupaten Probolinggo, Indonesia, and to explore associated risk factors for anemia, including nutritional status and supplementation practices. Materials and Methods: A community-based cross-sectional study was conducted in August 2024 as part of Universitas Airlangga’s Community Service Program. Pregnant women attending antenatal care in Sumber, Kabupaten Probolinggo were recruited based on ANC attendance and availability of hemoglobin test results. The "TAMENG" flipchart, designed with culturally relevant visuals and content on anemia prevention, was implemented during interactive education sessions. Demographic data, obstetric histories, and pre- and post-test knowledge assessments were collected. Statistical analysis was performed using chi-square tests to identify significant associations between variables. Results: Among 65 participants, 35.38% were anemic. Significant factors associated with anemia included nutritional status (60.9% of anemic women had mid-upper arm circumference Conclusion: The "TAMENG" flipchart effectively increased knowledge and awareness about anemia prevention. Tailored interventions addressing nutritional deficiencies, supplementation adherence, and family involvement can enhance maternal health outcomes in rural communities.

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: 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). Conclusion: The inverse expression pattern and reduction of 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.

Preeclampsia is a major cause of maternal mortality worldwide, with angiogenic imbalance playing a central role in its pathophysiology. This study aimed to investigate the relationship between the soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) ratio and oxygenation impairment in preeclamptic patients. A cross-sectional observational study was conducted on 47 women with singleton pregnancies diagnosed with preeclampsia at a gestational age beyond 34 weeks who underwent cesarean delivery. Data were obtained from medical records, including sFlt-1 and PlGF serum levels, sFlt-1/PlGF ratio, and arterial blood gas analysis for calculating PaO₂/FiO₂ (P/F) ratios. A significant negative correlation was found between the sFlt-1/PlGF ratio and the P/F ratio (r = -0.514, p < 0.001), indicating that a higher angiogenic imbalance is associated with poorer oxygenation status. Receiver operating characteristic (ROC) curve analysis revealed a cut-off value of 138.58 for the sFlt-1/PlGF ratio, with 83.33% sensitivity and 80% specificity for predicting oxygenation impairment. These findings suggest that the sFlt-1/PlGF ratio may serve as an early biomarker for detecting oxygenation disturbances in preeclampsia, supporting timely clinical interventions.

Polycystic ovary syndrome (PCOS) and obesity are prevalent conditions that independently impair fertility and increase the risk of adverse pregnancy outcomes. When coexisting, they present compounded challenges for conception and pregnancy management. We report a case of a 27-year-old primigravida with PCOS and class II obesity who achieved spontaneous conception after three years of infertility and multiple failed assisted reproductive attempts. Preconception lifestyle modifications and medical management improved insulin sensitivity and restored ovulatory function. Despite being categorized as a high-risk pregnancy, the antenatal course was unremarkable, with appropriate fetal growth and no major maternal or neonatal complications. Vaginal delivery occurred at term, resulting in a healthy newborn. This case highlights the potential for favorable reproductive and obstetric outcomes in women with PCOS and obesity through early diagnosis, lifestyle intervention, and meticulous prenatal care. It underscores the importance of individualized and multidisciplinary management strategies in optimizing maternal and fetal health. Spontaneous conception and favorable pregnancy outcomes are achievable in women with PCOS and obesity through comprehensive care. Early intervention and tailored monitoring play a crucial role in mitigating risks associated with these conditions.

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

We reported a case of late congenital cystic malformation (CCAM) diagnosis with problematic COVID-19 infected condition during delivery and dilemmatic neonatal management. A 24-year-old pregnant woman, second pregnancy, came very late in pregnancy (38 weeks gestational age), misdiagnosed with congenital diaphragmatic hernia. Our ultrasound examination revealed congenital cystic malformation type-1 in the right lung, with some of the normal lung lobes. The Left side lung was normal. CCAM volume ratio (CVR) 2,79 cm. Due to COVID-19 infection, our multidisciplinary team decided to perform quick chest tube insertion during the ex-utero intrapartum therapy (EXIT) procedure to avoid pneumothorax complications continued with intubation for the newborn. Neonatal middle right lung lobectomy was done after optimal condition at 20 days old with pathology anatomic result of CCAM type 1. The diagnosis, type, and prognosis of CCAM should be established earlier to make enough time for the better-prepared multidisciplinary management of the newborn.

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).