Betamethasone administration during pregnancy is associated with placental epigenetic changes with implications for inflammation

Background Glucocorticoids (GCs) play a pivotal role in fetal programming. Antenatal treatment with synthetic GCs (sGCs) in individuals in danger of preterm labor is common practice. Adverse short- and long-term effects of antenatal sGCs have been reported, but their effects on placental epigenetic characteristics have never been systematically studied in humans. Results We tested the association between exposure to the sGC betamethasone (BET) and placental DNA methylation (DNAm) in 52 exposed cases and 84 gestational-age-matched controls. We fine-mapped associated loci using targeted bisulfite sequencing. The association of placental DNAm with gene expression and co-expression analysis on implicated genes was performed in an independent cohort including 494 placentas. Exposure to BET was significantly associated with lower placenta DNAm at an enhancer of FKBP5. FKBP5 (FK506-binding protein 51) is a co-chaperone that modulates glucocorticoid receptor activity. Lower DNAm at this enhancer site was associated with higher expression of FKBP5 and a co-expressed gene module. This module is enriched for genes associated with preeclampsia and involved in inflammation and immune response. Conclusions Our findings suggest that BET exposure during pregnancy associates with few but lasting changes in placental DNAm and may promote a gene expression profile associated with placental dysfunction and increased inflammation. This may represent a pathway mediating GC-associated negative long-term consequences and health outcomes in offspring.

Successful Treatment of Placental Chorangiomas by Ultrasound-Guided Percutaneous in utero Microcoil Embolization

Placental chorangiomas can cause a high-output fetal state and increase neonatal morbidity and mortality. There is a paucity of data published describing the optimal treatment of these cases, and methods for occlusion to date include placement of vascular clips, bipolar cautery, injection of alcohol or surgical glue, interstitial laser, and microcoil embolization. We report 2 cases of prenatally diagnosed chorangiomas that caused a high-output fetal state and were successfully treated with microcoil embolization. This case series describes our technique and supports microcoil embolization as a potentially safe and effective antenatal treatment option in symptomatic chorangiomas.

Does Health Insurance Affect the Completeness of Antenatal Care?

The antenatal treatment has been ineffective in reducing maternal mortality. Therefore, this study aimed to examine health insurance effect on Indonesia's antenatal care quality. The 2017 Indonesian Demographic and Health Survey data were processed. Moreover, a sample size of 15,351 participants was selected using the analysis unit of study for women aged 15 to 49. In the final stage, Binary Logistic Regression was used, while other variables examined besides antenatal treatment included health insurance, residence, age, marital, education, parity, and wealth. Based on the complete category of antenatal care visits, women that did antenatal care visits were ≥ four, occupied by both types of health insurance ownership. The multivariable analysis indicated that health insurance ownership affects antenatal care completeness as insured women were 1.394 times higher than uninsured women (OR= 1.394; 95% CI= 1.257-1.546). Result showed other determinant variables, namely age, education, parity, and wealth were also found. In conclusion, health insurance gives Indonesian women a better possibility of receiving complete antenatal care.

Successful prenatal therapy of anti-CD36-mediated severe FNAIT by deglycosylated antibodies in a novel murine model

Recent studies have demonstrated that maternal anti-CD36 antibodies represent a frequent cause of fetal/neonatal alloimmune thrombocytopenia (FNAIT) in Asian and African populations. However, little is known about the pathomechanism and antenatal treatment of anti-CD36-mediated FNAIT. Here, we established a novel animal model to examine the clinical features of pups from immunized Cd36-/- female mice after breeding with wild-type male mice. Mild thrombocytopenia was observed, but high pup mortality was also documented (40.26%). IVIG (1 g/kg) administration on days 7, 12, and 17 to immunized Cd36-/- mothers after breeding reduced fetal death (12.70%). However, delaying the IVIG administration series on days 10, 15, and 20 did not reduce fetal death (40.00%). In contrast, injection of deglycosylated anti-CD36 (deg-anti-CD36) polyclonal antibodies (5 mg/kg) on days 10, 15, and 20 significantly reduced fetal death (5.26%). Subsequently, monoclonal antibodies (mAbs) against mouse CD36 were developed, and one clone producing high-affinity anti-CD36 (termed 32-106) effectively inhibited maternal antibody binding and was therefore selected. Using the same approach of deg-anti-CD36, the administration of deg-32-106 significantly reduced fetal death (2.17%). Furthermore, immunized Cd36-/- mothers showed placenta deficiency. Accordingly, maternal anti-CD36 antibodies inhibited angiogenesis of placenta endothelial cells, which could be restored by deg-32-106. In summary, maternal anti-CD36 antibodies caused a high frequency of fetal death in our animal model, associated with placental dysfunction. This deleterious effect could be diminished by the antenatal administration of IVIG and deg-mAb 32-106. Interestingly, treatment with deg-32-106 appears more beneficial considering the lower dose, later start of treatment, and therapy success.

The Effect of Prenatal and Postnatal Treatment with Intravenous Immunoglobulin on Severity of Neonatal Hemochromatosis: The Tale of Two Brothers (Case Report)

Background Neonatal hemochromatosis (NH) is a rare condition that was the main reason for liver transplantation in infants. With the realization that NH results from the fetal complement-mediated liver injury, intravenous immunoglobulins (IVIG) were successfully introduced for the treatment. Case Presentation We present two cases of NH from the same family to illustrate the role of antenatal treatment with IVIG in alleviation and possible prevention of this serious morbidity. Conclusion A prenatal treatment and early postnatal administration of IVIG are effective ways to manage NH that help to reduce the severity of the symptoms, prevent liver failure, and avoid the need for liver transplantation.

USE OF SLIDENAFIL CITRATE IN CASES OF INTRAUTERINE GROWTH RESTRICTION AT OBSTETRICS AND GYNAECOLOGY DEPARTMENT OF JLNMCH, BHAGALPUR, BIHAR

Objective: Intrauterine growth restriction (IUGR) is one of the most serious complications of pregnancy. Up to date, there is no evidence of achieving antenatal treatment of IUGR with abnormal placentation. Although, Sildenal citrate has shown promising results, there are no rm conclusion till now. The aim of our study is to evaluate the use of Sildenal citrate in the treatment of IUGR cases associated with impaired placental circulation. Materials And Methods: this was a prospective non-randomized study conducted at JLNMCH, Bhagalpur, Bihar starting from February 2019 to January 2020. The studied population included singleton pregnancy and suffering from IUGR associated with impaired placental circulation. Results: This study included 30 pregnant women. Cases were divided into two groups. The rst group received sildenal citrate and the second control group did not receive sildenal citrate. After 4 weeks after the 1st dose of Sildenal signicant decrease in umbilical artery Doppler indices. There was a statistically signicant difference in the mean birth weight at delivery and neonatal admission to the NICU in sildenal group. Conclusion: sildenale citrate treatment may present a new hope towards better perinatal outcomes for pregnancies complicated by IUGR and impaired placental circulation that may help to decrease neonatal admission to the NICU.

Modern methods of antenatal treatment of obstructive kidney disease in the fetus

The article considers published sources of domestic and foreign research concerning the etiology and pathogenesis of obstructive uropathology in the fetus, evaluation of the effectiveness of intrauterine surgical procedures for this pathology in the fetus in comparison with wait-and-see tactics of pregnancy management.