Human plasma pregnancy-associated miRNAs and their temporal variation within the first trimester of pregnancy

Background During pregnancy, maternal metabolism undergoes substantial changes to support the developing fetus. Such changes are finely regulated by different mechanisms carried out by effectors such as microRNAs (miRNAs). These small non-coding RNAs regulate numerous biological functions, mostly through post-transcriptional repression of gene expression. miRNAs are also secreted in circulation by numerous organs, such as the placenta. However, the complete plasmatic microtranscriptome of pregnant women has still not been fully described, although some miRNA clusters from the chromosome 14 (C14MC) and the chromosome 19 (C19MC and miR-371-3 cluster) have been proposed as being specific to pregnancy. Our aims were thus to describe the plasma microtranscriptome during the first trimester of pregnancy, by assessing the differences with non-pregnant women, and how it varies between the 4th and the 16th week of pregnancy. Methods Plasmatic miRNAs from 436 pregnant (gestational week 4 to 16) and 15 non-pregnant women were quantified using Illumina HiSeq next-generation sequencing platform. Differentially abundant miRNAs were identified using DESeq2 package (FDR q-value ≤ 0.05) and their targeted biological pathways were assessed with DIANA-miRpath. Results A total of 2101 miRNAs were detected, of which 191 were differentially abundant (fold change < 0.05 or > 2, FDR q-value ≤ 0.05) between pregnant and non-pregnant women. Of these, 100 miRNAs were less and 91 miRNAs were more abundant in pregnant women. Additionally, the abundance of 57 miRNAs varied according to gestational age at first trimester, of which 47 were positively and 10 were negatively associated with advancing gestational age. miRNAs from the C19MC were positively associated with both pregnancy and gestational age variation during the first trimester. Biological pathway analysis revealed that these 191 (pregnancy-specific) and 57 (gestational age markers) miRNAs targeted genes involved in fatty acid metabolism, ECM-receptor interaction and TGF-beta signaling pathways. Conclusion We have identified circulating miRNAs specific to pregnancy and/or that varied with gestational age in first trimester. These miRNAs target biological pathways involved in lipid metabolism as well as placenta and embryo development, suggesting a contribution to the maternal metabolic adaptation to pregnancy and fetal growth.

Nasobiliary drainage: an effective treatment for pruritus in cholestatic liver disease

IntroductionNasobiliary drains (NBDs) have been successfully used to manage intrahepatic cholestasis, bile leaks and obstructive cholangitis. It allows external drainage of bile, bypassing the ileum where bile salts are reabsorbed. We assessed the utility of placement with effect on markers of cholestasis and patient symptoms.MethodsConsecutive patients undergoing NBD over 12 years for the management of pruritus were retrospectively analysed. Recorded variables included patient demographics, procedural characteristics and response to therapy.ResultsTwenty-three patients (14, 61% male) underwent 30 episodes of NBD. The median age was 26 years old (range 2–67 years old). A single procedure was carried out in 20. One patient each had two, three and five episodes of NBD. The most common aetiologies were hereditary cholestatic disease (n=17, 74%) and drug-induced cholestasis (n=5, 22%),NBD remained in situ for a median of 8 days (range 1–45 days). Significant improvement in bilirubin was seen at 7 days post-NBD (p=0.0324), maintained at day 30 (335 μmol/L vs 302 µmol/L vs 167 µmol/L). There was symptomatic improvement in pruritus in 20 (67%, p=0.0494) episodes. One patient underwent NBD during the first trimester of pregnancy after medical therapy failure with a good symptomatic response. The catheters were well tolerated in 27 (90%) of cases. Mild pancreatitis occurred in 4 (13%) cases.ConclusionNBD can be used to provide symptomatic improvement to patients with pruritus associated with cholestasis. It is well tolerated by patients. They can be used in pregnancy where medical management has failed.

Diagnostic role of uterine artery dopplerometry in the first trimester of pregnancy

A Doppler sonographic examination of blood flow in the left and right uterine arteries was carried out in women in the first trimester of pregnancy. Systolic- diastolic ratio (S/D) andpulsative index (PI) were assessed in 71 women with physiological course of pregnancy and in 49 women with threatened abortion. The investigation revealed clear connection of the uterine blood flow lateralization and corpus luteum localization. These interrelations are characterized differently in case of physiological pregnancy and threatened abortion. The new approach to the evaluation of uterine blood flow gives an ability ofpreclinical diagnostics of threatened abortion.

NICE guideline “Ectopic pregnancy and miscarriage”: new changes and importance for the clinicist

The purpose of this publication is to summarize the current data on the effectiveness of progestogens in patients with threatened miscarriage (vaginal bleeding in the first trimester of pregnancy) and to review the updated UK National Institute for Health and Care Excel (NICE) clinical guidelines on ectopic pregnancy and miscarriage.In accordance with the opinion of the Cochrane Society experts and the updated NICE clinical guidelines for 2021, vaginal progesterone at a dose of 800 mg/day is the only intervention that has been shown to be effective in increasing live births compared to placebo for women with one or more previous miscarriages and early vaginal bleeding (relative risk 1.08, 95% confidence interval 1.02–1.15, high certainty evidence). Upon confirmation of fetal heartbeat, this treatment should be extended until 16 weeks of gestation.There is still uncertainty over the effectiveness and safety of alternative progestogen treatments (as dydrogesterone) for threatened and recurrent miscarriage. There is also no evidence of benefit of any other preparations or doses of progesterone in patients at risk of miscarriage.

Efficiency of early monitoring gestational process in women with risk of pregnancy loss

This article is devoted to optimization of dispensary observation at the eshlia terms of gestation of women suffer from sporadic miscaniages in anamnesis as well as tlie definition of prognostic meaning of the ultmsonic doppleromet-ry criterias, the enzyme activity of lisosomal of blood plasma and tlie cytochemical mte (DCR) for tlie segmentnuclear leucocytes at the pregnant women witli pathological obstetl'ic anamnesis. 13 7p1-egnant women were tested, 98 o f them at the earlier terms o f gest-ation from 7 to 14 weelis of t-heir pregnancy. The received data show that metabolic conection and normalization of microbiocenosis of vagina and cavix channel in tlie first trimester of pregnancy is pathogen validity, they promot-e tlie nmwaf pregnancy of the next terms of gestation and decrease tlie frequency of repeat-ed misriages

A Pragmatic Intervention Using Financial Incentives for Pregnancy Weight Management: Feasibility Randomized Controlled Trial

Background Excessive gestational weight gain (GWG) is common and can result in maternal and child health complications. Pragmatic behavioral interventions that can be incorporated into standard obstetric care are needed, and financial incentives are a promising approach. Objective The aim of this study is to evaluate the feasibility of recruitment, randomization, and retention, as well as treatment engagement and intervention satisfaction, in a behavioral program. The program provided small incentives for meeting behavioral goals of self-weighing and physical activity as well as larger outcome incentives for meeting GWG goals. Methods We recruited 40 adult women in their first trimester of pregnancy from February 2019 to September 2019 at an obstetric clinic. Participants were randomized to 3 intervention components using a 2×2×2 factorial design: daily incentives for self-weighing (lottery vs certain loss), incentives for adhering to the Institute of Medicine’s GWG guidelines based on BMI category (monthly vs overall), and incentives for reaching physical activity goals (yes vs no). Participants were asked to complete daily weigh-ins using the Withings Body wireless scale provided by the study, as well as wear a physical activity tracker (Fitbit Flex 2). Feasibility outcomes of recruitment, randomization, and retention, as well as treatment engagement and intervention satisfaction, were assessed. Weight assessments were conducted at baseline, 32-week gestation, and 36-week gestation. Results Participants were enrolled at, on average, 9.6 (SD 1.8) weeks’ gestation. Of the 39 participants who were oriented to their condition and received the intervention, 24 (62%) were Black or African American, 30 (77%) were not married, and 29 (74%) had an annual household income of less than US $50,000. Of the 39 participants, 35 (90%) completed the follow-up data collection visit. Participants were generally quite positive about the intervention components, with a particular emphasis on the helpfulness of, and the enjoyment of using, the e-scale in both the quantitative and qualitative feedback. Participants who received the loss incentive, on average, had 2.86 times as many days of self-weighing as those who received the lottery incentive. Participants had a relatively low level of activity, with no difference between those who received a physical activity incentive and those who did not. Conclusions A financial incentive–based pragmatic intervention was feasible and acceptable for pregnant women for promoting self-weighing, physical activity, and healthy GWG. Participants were successfully recruited early in their first trimester of pregnancy and retained for follow-up data collection in the third trimester. Participants demonstrated promising engagement in self-weighing, particularly with loss-based incentives, and reported finding the self-weighing especially helpful. This study supports further investigation of pragmatic, clinic-based financial incentive–based interventions for healthy GWG behaviors. Trial Registration ClinicalTrials.gov NCT03834194; https://clinicaltrials.gov/ct2/show/NCT03834194

Effects of Cigarette Smoke Exposure on Placental Global DNA Methylation and 8-hydroxy-2’-deoxyguanosine Levels in Mother-new-born Binomials

Background: Smoking is practiced worldwide for both men and women, and it is associated with different diseases and deleterious effects on gestational products, chiefly during pregnancy. Epigenetic alterations induced by cigarette smoke must be related to perinatal abnormalities. Methods: 219 pregnant women, aged 16 to 34 years, with or without a history of cigarette consumption (1–5/day) during the first trimester of pregnancy and their offspring were studied in this work. A validated dietary questionnaire was used to estimate daily consumptions of macronutrients and micronutrients, including total energy, during pregnancy. As a marker of DNA damage, 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels were determined in plasma of women, before delivery, in umbilical cord blood after delivery, in the new-borns. The proportion of methylated DNA in the placentas (metDNA) was determined by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). Results: Non-significant differences were observed between smoking and non-smoking women groups, or between the new-borns groups (p > 0.05). Smoking women showed up higher intakes of vitamins, lipids, proteins, and carbohydrates in comparison with non-smoking women (p < 0.01). 8-OHdG levels correlated among the mothers and new-borns (p = 5.386e-15) and were lower in the smoking binomials in comparison with non-smoking binomials (β = −1.20 to −64). Negative correlations were found between micronutrients and macronutrients but Vitamin C, and 8-OHdG levels of the women (p < 0.01). However, the new-borns 8-OHdG correlated with proteins, vitamin A, and vitamin B12 (p < 0.05). Cigarettes consumed per day correlated to the 8-8HdG levels (Rho = −0.247, p = 0.012), alcohol consumption (Rho = 0.219, p = 0.001), to macronutrients (Rho = 212 to 332, p < 0.01), micronutrients (Rho = 186 to 289, p < 0.01), and to energy (Rho = 0.286, p = 0.001). Finally, metDNA deceased in the smoking women than in the non-smoking women (β = −0.12, p < 0.05), and correlated with the number of cigarettes consumed per day (Rho = −0.229, p = 0.009). Conclusion: Cigarette smoking alters metDNA levels of the placenta, however, their clinical effects come out over years or transgenerationally.

Púrpura trombocitopénica idiopática en el embarazo: a propósito de un caso

Idiopathic purple thrombocytopenia is a hemorrhagic pathology, characterized by a decrease in the platelet count during pregnancy, mediated by cells and anti-platelet antibodies, causing the premature destruction of platelets by the reticuloendothelial system, which during pregnancy could lead to a commitment to maternal fetal wellbeing in severe stages. This pathology occurs in 1 out of every 1,000 to 10,000 pregnancies, and corresponds to 3% of thrombocytopenic pregnancies. The goal of management is to maintain platelet counts within safe ranges, recommending starting harmacological management when a platelet count lower than 10,000 / uL is found at any time during pregnancy or 30,000 / uL in the second or third trimester. The case presented corresponds to a 40-yearold woman in the first trimester of pregnancy with a history of chronic idiopathic purple thrombocytopenic, with severe thrombocytopenia at the time of admission to the Hospital. Keywords: Idiopathic thrombocytopenic purpura. Pregnancy. Blood platlets.

Screening for Vaginal and Endocervical Infections in the First Trimester of Pregnancy? A Study That Ignites an Old Debate

Objectives: Vaginal and endocervical infections are considered a global health problem, especially after recent evidence of their association with preterm delivery and other adverse obstetric outcomes. Still, there is no consensus on the efficacy of a screening strategy for these infections in the first trimester of pregnancy. This study evaluated their prevalence and whether screening and treatment resulted as effective in reducing pregnancy and perinatal complications. Methods: A single-center prospective observational study was designed; a sample size of 400 first-trimester pregnant women was established and they were recruited between March 2016–October 2019 at the Puerta de Hierro University Hospital (Spain). They were screened for vaginal and endocervical infections and treated in case of abnormal flora. Pregnancy and delivery outcomes were compared between abnormal and normal flora groups by univariate analysis. Results: 109 patients had an abnormal flora result (27.2%). The most frequently detected infection was Ureaplasma urealyticum (12.3%), followed by Candida spp. (11.8%), bacterial vaginosis (5%), Mycoplasma hominis (1.2%) and Trichomonas vaginalis (0.8%). Patients with abnormal flora had a 5-fold increased risk of preterm premature rupture of membranes (5.3% vs. 1.1% of patients with normal flora, Odds Ratio 5.11, 95% Confidence Interval 1.20–21.71, p = 0.028). No significant differences were observed regarding preterm delivery or neonatal morbidity. Conclusions: Considering the morbimortality related to prematurity and that the results of our study suggest that the early treatment of abnormal flora could improve perinatal outcomes, the implementation of a screening program during the first trimester should be considered.