Placental Protein 13 and Syncytiotrophoblast Basement Membrane Ultrastructures in Preeclampsia.

Background and Objectives: Preeclampsia has been linked to an inflammatory response that may be brought on by endothelial cell dysfunction. This paper investigates the pathomechanism of syncytiotrophoblast basement membrane (STBM) damage and Placental Protein 13 (PP13) release, which may have a role in systemic endothelial dysfunction in preeclampsia. Materials and Methods: This comparative cross-sectional study involves 54 preeclampsia patients (27 early-onset preeclampsia and 27 late-onset preeclampsia) and 27 pregnant women with normal blood pressure. An enzyme-linked immunosorbent assay was performed to evaluate maternal blood levels of PP13. Following birth, a portion of the placenta was collected for transmission electron microscope (TEM) and immunohistochemical (IHC) analysis. The data were analyzed using STATA version 15. Results: PP13 expression in the placental syncytiotrophoblast was significantly lower in the early-onset preeclampsia, compared to late-onset preeclampsia and normotensive pregnancy, group (p < 0.001). In contrast, serum PP13 levels were found to be the highest in the early-onset preeclampsia group, although no significant difference were found in mean maternal serum levels of PP13 between the three groups. The decreased PP13 expression in placental syncytiotrophoblast can be attributed to the greater extent of damage in the STBM in early-onset preeclampsia that leads to the release of a larger amount of PP13 into maternal circulation. The hypothesis aligns with the TEM analysis results. Preeclamptic pregnancies showed placental syncytiotrophoblast aponeurosis, whereas normotensive pregnancies did not. Placental lesions and STBM shedding were found to be more pronounced in early-onset preeclampsia compared to late-onset preeclampsia. Conclusions: PP13 and STBM damage may play a role in systemic endothelial dysfunction in preeclampsia.

Deep Learning for Improving the Effectiveness of Routine Prenatal Screening for Major Congenital Heart Diseases.

Early prenatal screening with an ultrasound (US) can significantly lower newborn mortality caused by congenital heart diseases (CHDs). However, the need for expertise in fetal cardiologists and the high volume of screening cases limit the practically achievable detection rates. Hence, automated prenatal screening to support clinicians is desirable. This paper presents and analyses potential deep learning (DL) techniques to diagnose CHDs in fetal USs. Four convolutional neural network architectures were compared to select the best classifier with satisfactory results. Hence, dense convolutional network (DenseNet) 201 architecture was selected for the classification of seven CHDs, such as ventricular septal defect, atrial septal defect, atrioventricular septal defect, Ebstein's anomaly, tetralogy of Fallot, transposition of great arteries, hypoplastic left heart syndrome, and a normal control. The sensitivity, specificity, and accuracy of the DenseNet201 model were 100%, 100%, and 100%, respectively, for the intra-patient scenario and 99%, 97%, and 98%, respectively, for the inter-patient scenario. We used the intra-patient DL prediction model to validate our proposed model against the prediction results of three expert fetal cardiologists. The proposed model produces a satisfactory result, which means that our model can support expert fetal cardiologists to interpret the decision to improve CHD diagnostics. This work represents a step toward the goal of assisting front-line sonographers with CHD diagnoses at the population level.

Decidual dendritic cells 10 and CD4+CD25+FOXP3 regulatory T cell in preeclampsia and their correlation with nutritional factors in pathomechanism of immune rejection in pregnancy.

BACKGROUND: Immune intolerance is thought to be the underlying cause of immune rejection to fetus in preeclampsia. Decidual dendritic cell-10 (DC-10) and T regulator cell (Treg) play important role to create tolerogenic environment during pregnancy. However, their roles on the specific pathomechanism of preeclampsia along with various nutritional factors have not been widely studied. AIM: To determine the number of DC-10 and Treg in preeclampsia and their correlations with decidual nutritional factors. METHOD: This was a cross-sectional study among early onset preeclampsia (EOPE), late onset preeclampsia (LOPE), and normotensive (NT) pregnancies. Decidual specimens were obtained by curettage after caesarean section. The number of DC-10 and Treg cells were counted using flow cytometry. The levels of nutritional factors (zinc, retinol, all-trans retinoic acid, vitamin D) were determined using ICP-MS and LC-MS method. RESULT: A total of 14 subjects for each group were included in the study. The DC-10 was significantly lower in both EOPE and LOPE compared to NT (p < 0.001). Treg cells were significantly higher in EOPE compare to NT (p = 0.015). There was a moderate correlation between zinc level and DC-10 (p = 0.011) and a strong correlation between retinol level and DC-10 (p = 0.002) in the NT group. A moderate correlation was found between vitamin D level and Treg cells in the NT group (p = 0.026). CONCLUSION: There was a lower number of DC-10 and higher number of Treg cells in early preeclampsia. There was no correlation between DC-10 and Treg number with decidual nutritional factors in preeclampsia.

Cell-free fetal DNA as a non-invasive method using pyrosequencing in detecting beta-globin gene mutation: A pilot study from area with limited facilities in Indonesia.

Background: Thalassemia is a monogenic, autosomal recessive, inherited disorder of the red blood cells caused by mutations or deletions in the globin gene. Approximately 6-10% of the Indonesian population carries the ß-globin gene mutation; however, premarital screening is rarely conducted, and antenatal screening is optional. We explored the use of cell-free fetal DNA (cffDNA) as a potential non-invasive method of detecting the fetal ß-globin gene mutation prenatally in pregnant women. Materials and methods: Pregnant mothers (n = 10), who were known carriers of thalassemia and who had a history of having borne a baby with thalassemia major, and their carrier husbands (n = 4) were recruited after providing consent. EDTA blood was drawn, and maternal DNA, including cffDNA, and paternal DNA were isolated. Maternal contamination tests were conducted using the variable number tandem repeat test for ApoB and D1S80 loci. Allele quantification was performed by pyrosequencing. Known mutations from the bio-archived DNA of patients with thalassemia major (n = 16) were run alongside as a control. Results: In total, 7 out of 10 cffDNA successfully passed the maternal contamination test. The results of the allele quantification showed that six fetuses were predictive carriers of IVS1nt5 and one was predictive normal, in line with the allele quantification for the bio-archived DNA from patients with thalassemia major. The minimum threshold percentage for mutant A allele at cd26 was 32%, mutant T allele at IVS1nt1 was 23%, and mutant C allele at IVS1nt5 was 39%. Conclusion: Taking cffDNA from the mother's blood proved useful as a non-invasive means of detecting the ß-globin gene mutation using pyrosequencing allele quantification. This non-invasive method is of great interest for prenatal diagnosis in settings with limited facilities, as it minimizes the risk of abortion. Further study of other mutations of the ß-globin gene is needed.

Anemia Prevalence after Iron Supplementation among Pregnant Women in Midwifes Practice of Primary Health Care Facilities in Eastern Indonesia.

BACKGROUND: Iron deficiency anemia (IDA) in pregnant women is common, and iron supplementation is given during pregnancy to reduce birth complication. This study aimed to explore the prevalence of anemia and type of anemia after iron supplementation among pregnant women in the eastern part of Indonesia. METHODS: A cross-sectional study design was conducted between January and March 2019 in three Primary Health Care (PHC) facilities at Kupang, West Timor. After consent, pregnant women who had taken their iron supplementation for at least 3 months were asked for iron pills intake by using a self-designed questionnaire and by counting the pills leftover. Complete blood count examination was performed, and the type of anemia was assessed using Shine and Lal index (SLI; MCV ∗ MCV ∗ MCH/100) to determine whether anemia was due to iron deficiency or ß-thalassemia trait (ß-TT). In a subset of iron tablets distributed in the PHCs, Fe-concentration was measured. RESULTS: Of 102 pregnant women included, only 25.5% had taken the pills with a pill count of >80%. Interestingly, Fe-concentration in the pills from three different PHC facilities varied between 75% and 100%. After iron supplementation, however, anemia was detected in 34.3%, and based on SLI, 14.7% was suspected because of iron deficiency and 19.6% was suspective of ß-TT. Of note, nonanemic pregnant women (17.6%) had also low SLI, suggesting ß-TT or other hemoglobinopathies. CONCLUSION: Assessment of Shine and Lal index as the first step to screen the type of anemia in pregnant women from a limited area is of potential value, especially because Indonesia is located in the thalassemia belt area. An integrative approach and counseling among pregnant women with ß-TT and their partners will increase thalassemia awareness and optimal birth management.

The Difference in Maternal Serum Hypoxia-Inducible Factors-1α Levels between Early Onset and Late-Onset Preeclampsia.

BACKGROUND: Preeclampsia can be divided into early (EOPE) and late (LOPE) onset preeclampsia. Preeclampsia is related to the failure of placentation. Accumulation of hypoxia-inducible factors (HIF)-1α is commonly an acute and beneficial respond to hypoxia, while chronically elevated is associated with preeclampsia. AIM: This study aims to evaluate the serum levels of HIF-1α in preeclampsia and normal pregnancy, and to compare the difference between early-onset and late-onset preeclampsia. METHODS: A cross-sectional comparative study was conducted among a total of 69 pregnant women at ≥ 20 weeks of gestation, were recruited at obstetrics and gynaecology department at Dr M. Djamil Padang Hospital, network hospitals, health centres. They were divided into three groups early-onset preeclampsia, late-onset preeclampsia, and normal pregnancy. Preeclampsia was diagnosed using International Guidelines. Data were analysed by SPSS 24 program; data are presented as median and range or as mean ± standard deviation. One-way ANOVA test was used to determine the relationship between HIF-1α levels with the onset of preeclampsia. RESULTS: The results showed that the mean maternal serum HIF-1α levels in early-onset preeclampsia (EOPE), late-onset preeclampsia (LOPE), and normal pregnancy were 1366.96 ± 733.40 pg/ml, 916.87 ± 466.06 pg/ml, and 716.77 ± 541.08 pg/ml. Serum HIF-1α levels were higher in early-onset preeclampsia (EOPE), and late-onset preeclampsia (LOPE) compared to normal pregnancy. Among preeclampsia patients, serum HIF-1α was higher in EOPE than LOPE women. Statistical analysis revealed a significant difference in mean maternal serum HIF-1α between early-onset preeclampsia, late-onset preeclampsia, and normal pregnancy (p < 0.05). CONCLUSION: This study concluded that there is a significantly different level of HIF-1α between in early-onset preeclampsia, late-onset preeclampsia and normal pregnancy. Early-onset preeclampsia is the highest levels of serum HIF-1α.

Endothelial dysfunction in the young adult: a retrospective cohort study on the effect of low birth weight.

AIM: to investigate the effect of low birth weight (LBW) on endothelial function, and to determine the role of plasma adiponectin in endothelial dysfunction by conducting flow mediated brachial artery (FMBA) test or vasodilation response (VR) and by measuring plasma asymmetrical dimethylarginine (ADMA) of young adults born with LBW. METHODS: in a retrospective cohort study, subjects were randomly selected from the growth study cohort of Tanjungsari Sumedang district West Java. They consisted of 67 LBW and 67 NBW (Normal Birth Weight) young adults. Dependent variables were plasma adiponectin, plasma ADMA, and VR. The correlation between plasma adiponectin and ADMA level was examined using Pearson's correlation. RESULTS: the relative risk for LBW to have low brachialis artery vasodilation response was 2.94, (95% CI:1.91-4.53), and to have low of plasma adiponectin concentration 1.53, (95% CI: 1.07-2.18). There was a statistically significant difference for all variables studied (FMBA, plasma ADMA, and plasma Adiponectin concentrations), while simultaneous confidence interval measurements indicated that the value of FMBA and the concentration of plasma adiponectin were significantly lower, respectively p<0.001, 95% CI: -4.409-(-2.114), and p=0.015, 95% CI: -1.083-(-0.082) in LBW compared to NBW subjects. The correlation between plasma adiponectin concentration and plasma ADMA concentration in LBW subjects was not significant. CONCLUSION: there is an effect of LBW on endothelial function. LBW compared to NBW subjects have lower VR and plasma adiponectin concentration. There may be a small role of plasma adiponectin in endothelial dysfunction of young adults with LBW.

Severe α-thalassemia intermedia due to a compound heterozygosity for the highly unstable Hb Adana (HBA2: c.179G>A) and a novel codon 24 (HBA2: c.75T>A) mutation.

We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T > A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G > A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value.

The role of maternal & fetal doppler in pre-eclampsia.

Pre-eclampsia is associated with significant maternal and fetal morbidity and mortality worldwide. Pregnancy complicated by preeclampsia and/or by fetal growth restriction are reported to have inadequate maternal vascular responses to placentation. This defective vascular response was due to the failure of second wave of endovascular trophoblast migration leading to both a reduced amount and depth of trophoblast invasion of myometrium followed by the development of placental hypoxia and ischemia that can be measured biophysically by means of Doppler Ultrasound. The role of Doppler in the screening and management of preeclampsia would be reviewed in here focusing on uterine artery, umbilicalartery (UA), middle cerebral artery (MCA) and ductus venosus (DV) waveforms. The commonly used flow velocity waveform (FVW) spectrum is used namely resistance index (RI), systolic/diastolic ratio (S/D) or pulsatility index (Pl). The presence or persistence of an early diastolic notch of uterine artery over 24 weeks of pregnancy is predictive of subsequent preeclampsia and or IUGR later on. Umbilical artery Pl falls with gestational age, although mean Pl is relatively stable after 30 weeks gestation. While elevated indices are predictive of adverse outcome, absent or reversed end-diastolic velocities (AREDV) are of particular significance for growth restriction. Mean MCA Pl increases to approximately 28weeks gestation and then falls to term. Progressive hypoxemia results in a reduction in MCA Pl and therefore values 5th centile are regarded as abnormal. The ratio of UA/MCA Pl has been widely used as an index of cerebral redistribution. The 9 51h centile for pulsatility index for vein (PIV) of ductus venosus FVW falls from 0.9 at 20 weeks to 0.7 at term, with values above this being regarded as abnormal. The absence or reversal of atrial systolic forward flow of DV FVW are of particular clinical significance. By using Doppler in the early detection of preeclampsia and its fetal complication namely growth restriction we can arrange the management decisions and monitoring strategy for preeclampsia.