The vascular endothelial growth factor (VEGF) family is important for establishing normal pregnancy, and related single nucleotide polymorphisms (SNPs) are implicated in abnormal placentation and preeclampsia. We evaluated the association between preeclampsia and several VEGF SNPs among Filipinos, an ethnically distinct group with high prevalence of preeclampsia. The genotypes and allelic variants were determined in a case-control study (191 controls and 165 preeclampsia patients) through SNP analysis of VEGF-A (rs2010963, rs3025039) and VEGF-C (rs7664413) and their corresponding receptors VEGFR1 (rs722503, rs12584067, rs7335588) and VEGFR3 (rs307826) from venous blood DNA. VEGF-A rs3025039 C allele has been shown to associate with preeclampsia (odds ratio of 1.648 (1.03-2.62)), while the T allele bestowed an additive effect for the maintenance of normal, uncomplicated pregnancy and against the development of preeclampsia (odds ratio of 0.62 (0.39-0.98)). VEGFR1 rs722503 is associated with preeclampsia occurring at or after the age of 40 years. The results showed that genetic variability of VEGF-A and VEGFR1 are important in the etiology of preeclampsia among Filipinos.
Objectives. The effect of COVID-19 infection in pregnant women and her neonate is not well-understood, with no clear evidence for vertical transmission. This study aims to determine the maternal and neonatal clinical characteristics and the dyad’s outcomes among those infected with COVID-19 infection. Methods. An ambispective cross-sectional study involving pregnant women with confirmed COVID-19 infection was conducted at the Philippine General Hospital from April to August 2020. Two hundred nine obstetric patients were included, 14 of whom consented to specimen collection to determine vertical transmission. Results. The majority of pregnant women with COVID-19 infection and their neonates had good outcomes. Labor, delivery, and the immediate postpartum course were generally uneventful. The all-cause maternal morbidity rate was high at 75.6 per 100 cases during the five-month study period. COVID-19 related morbidities included the development of Guillain-Barré Syndrome. The in-hospital all-cause maternal mortality rate was 1.91 per 100 cases. The causes of maternal death were acute respiratory failure, septic shock, and congenital heart disease (atrial septal defect with Eisenmengerization). The in-hospital, all-cause neonatal mortality rate was 1.04 per 100 neonates of cases. The lone mother and infant deaths were in a postmortem rt-PCR swab negative mother with an rt-PCR swab positive live neonate who eventually succumbed after nine days of life. All 14 dyads with collected specimens that included amniotic fluid, placental tissue, umbilical cord, and neonate nasopharyngeal swab tested negative for SARS-CoV-2 rt-PCR. Conclusion. The prognosis for COVID-19 infected pregnant patients was generally good, with most of the patients discharged improved. Almost all of the neonates born to COVID-19-infected mothers were stable-term infants. There was no evidence for vertical transmission, as shown by negative rt-PCR results for all the additional specimens obtained. In general, the prognosis for COVID-19 infected dyads was good. The majority of the mothers were discharged well with their term infants. All possible maternal sources of COVID-19 infection to the neonate tested negative. This study provided no evidence for vertical transmission.
Preterm birth remains to be one of the most prevalent obstetric complications worldwide. Since there are multiple etiological factors associated with this disease process, an integrative literature search in PubMed and Scopus databases on possible mechanism of action and effect of bisphenols on exposure on human or animal placental samples in preterm birth was conducted. From 2332 articles on initial literature search, 63 studies were included for full data extraction. Altogether, several pathways were shown to be possibly affected by bisphenols, leading to dysregulations in structural and endocrine foundation in the placenta, potential induction of senescence and failure of decidualization in the decidua, and possible propagation of inflammation in the fetal membranes. Combined, these actions may eventually counteract bisphenol-induced relaxation of the myometrium and promote contractility alongside fetal membrane weakening. In totality, these individual impairments in gestation-critical processes may lead to failure of maintenance of pregnancy, and thus effecting preterm birth.
Preeclampsia is one of the major hypertensive diseases of pregnancy. Genetic factors contribute to abnormal placentation. The inadequate transformation of cytotrophoblasts causes failure of maternal spiral arteries’ remodeling and results in narrow, atherotic-prone vessels, leading to relative placental ischemia. This study aims to explore the possibility of identifying dysregulated gene networks that may offer a potential target in the possible prevention of preeclampsia. We performed a weighted gene correlated network analysis (WGCNA) on a subset of gene expression profiles of placental tissues from severe preeclamptic pregnancies. We identified a gene module (number of genes = 402, GS = 0.35, p = 0.02) enriched for several G-protein-coupled receptor (GPCR)-related genes with significant protein–protein molecular interaction (number of genes = 38, FDR = 0.0007) that may play key roles in preeclampsia. Some genes are noted to play key roles in preeclampsia, including LPAR4/5, CRLR, NPY, TACR1/2, and SFRP4/5, whose functions generally relate to angiogenesis and vasodilation or vasoconstriction. Other upregulated genes, including olfactory and orexigenic genes, serve limited functions in the disease pathogenesis. Altogether, this study shows the utility of WGCNA in exploring possible new gene targets, and additionally reinforces the feasibility of targeting GPCRs that may offer intervention against development and disease progression among severe preeclampsia patients.
Preterm birth remains a problem globally, as multiple factors contribute to its etiology and pathogenesis. One such factor is the exposure to environmental toxicants, in which recent literature has described contributory roles in disease progression. This study aims to show research trends and collaborations in papers related to environmental toxicants and preterm birth through a bibliometric analysis to determine hot spots for research as well as to identify already established themes that can point to policy making and development. Using the Scopus database, we were able to identify 956 original research articles from 72 countries between 1955 and 2021; bibliographic information was exported, analyzed, and visualized using Bibliometrix and VOSviewer. There was an annual growth of research and reporting in this area, which significantly increased within the last two decades. The top countries that have published on this topic include the USA (n = 343), China (n = 103), and Australia (n = 43), with strong international collaboration in reports from China. Top journals for publication include Environmental Research (n = 53), Environmental Health Perspectives (n = 47), and Environment International (n = 46). Previous literature focused on establishing toxicants that are significantly associated with preterm birth, with current research focusing on molecular mechanisms of environmental toxicants. Overall, our bibliometric analysis gives a scoping view of the existing research landscape in terms of environmental health and preterm birth.
BackgroundMultiple interrelated pathways contribute to the pathogenesis of preeclampsia, and variants in susceptibility genes may play a role among Filipinos, an ethnically distinct group with high prevalence of the disease. The objective of this study was to examine the association between variants in maternal candidate genes and the development of preeclampsia in a Philippine population.MethodsA case-control study involving 29 single nucleotide polymorphisms (SNPs) in 21 candidate genes was conducted in 150 patients with preeclampsia (cases) and 175 women with uncomplicated normal pregnancies (controls). Genotyping for the GRK4 and DRD1 gene variants was carried out using the TaqMan Assay, and all other variants were assayed using the Sequenom MassARRAY Iplex Platform. PLINK was used for SNP association testing. Multilocus association analysis was performed using multifactor dimensionality reduction (MDR) analysis.ResultsAmong the clinical factors, older age (P < 1 × 10–4), higher BMI (P < 1 × 10–4), having a new partner (P = 0.006), and increased time interval from previous pregnancy (P = 0.018) associated with preeclampsia. The MDR algorithm identified the genetic variant ACVR2A rs1014064 as interacting with age and BMI in association with preeclampsia among Filipino women.ConclusionsThe MDR algorithm identified an interaction between age, BMI and ACVR2A rs1014064, indicating that context among genetic variants and demographic/clinical factors may be crucial to understanding the pathogenesis of preeclampsia among Filipino women.Electronic supplementary materialThe online version of this article (10.1186/s12884-018-2152-z) contains supplementary material, which is available to authorized users.
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