Pharmacokinetics and Safety of the Integrase Inhibitors Elvitegravir and Dolutegravir in Pregnant Women With HIV

2019 ◽  
Vol 53 (8) ◽  
pp. 833-844 ◽  
Author(s):  
Binh Nguyen ◽  
Michelle M. Foisy ◽  
Christine A. Hughes
Keyword(s):  
Pregnant Women ◽  
English Language ◽  
Data Extraction ◽  
Plasma Concentrations ◽  
Safety Data ◽  
First Trimester ◽  
Pharmacokinetic Data ◽  
Increased Risk ◽  
Women With Hiv ◽  
In Pregnancy

Objective: To synthesize data on the pharmacokinetics and safety of dolutegravir and elvitegravir in pregnant women living with HIV. Data Sources: A PubMed, EMBASE, Web of Science, and Google Scholar literature search (January 2010 to December 2018) was performed using the search terms dolutegravir, elvitegravir, women, pregnant*, and HIV. Additional reports were identified from conference abstracts and review of reference lists. Study Selection and Data Extraction: English-language studies reporting pharmacokinetic and/or safety data in pregnant women receiving dolutegravir or elvitegravir/cobicistat were included. Data Synthesis: A total of 17 studies were selected. Studies demonstrated a modest decrease in dolutegravir concentrations in pregnancy. Preliminary data suggest an increased risk of neural tube defects when dolutegravir is used at the time of conception. Available pharmacokinetic data in pregnant women showed significantly reduced plasma concentrations of elvitegravir/cobicistat which may increase the risk of virological failure. Current guidelines recommend that dolutegravir should not be initiated in women who have the potential to become pregnant or women in their first trimester of pregnancy and elvitegravir/cobicistat should be avoided during pregnancy. Relevance to Patient Care and Clinical Practice: This review highlights pharmacokinetic and safety data for dolutegravir and elvitegravir/cobicistat in pregnant women. Clinicians need to be aware of these data to convey the risks and benefits of using these agents in women of child-bearing potential. Conclusions: Changes in guideline recommendations reflect emerging data regarding the use of dolutegravir and elvitegravir/cobicistat in pregnancy. Until further information is available, raltegravir or other first-line agents are recommended for women with HIV planning to become pregnant.

scholarly journals First trimester uric acid level: a reliable marker for gestational diabetes mellitus

2019 ◽  
Vol 8 (6) ◽  
pp. 2358
Author(s):  
Suvarna Jyothi Ganta ◽  
Sunanda R. Kulkarni
Keyword(s):  
Diabetes Mellitus ◽  
Uric Acid ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Pregnant Women ◽  
Serum Uric Acid ◽  
First Trimester ◽  
Family History Of Diabetes ◽  
Increased Risk ◽  
In Pregnancy

Background: The prevalence of diabetes mellitus (DM) is increasing worldwide and more in developing countries like India. The diabetic epidemic experienced in India can be due to strong genetic factors coupled with increasing urbanization, sedentary lifestyle, changes in the dietary patterns and increasing obesity. Indians are at an 11-fold increased risk of developing gestational glucose intolerance and hence universal screening is essential. Uric acid is a known marker of oxidative stress. Hyperuricemia in early pregnancy may be an indicator of the existing metabolic disturbance which can hinder the maternal physiological adaptations generally seen in pregnancy thus making the pregnant women more vulnerable to the development of gestational diabetes mellitus. The objective of this study was to investigate the association between elevated uric acid levels in the first trimester of pregnancy with gestational diabetes.Methods: This prospective observational study was conducted in Chinmaya mission hospital, Bangalore from June 2016 to March 2017 (10 months). Three hundred and twelve (312) pregnant women of gestational age less than 12 weeks who attended the OBG outpatient department within this time of period for regular antenatal check-up were enrolled in the study. Along with the other antenatal investigations serum uric acid levels were estimated before 12 weeks and also between 24-28 weeks. At 24-28 weeks screening for GDM was done by OGCT using 75 gms of glucose (IADPISG criteria). Other parameters like age, parity, BMI, family history of diabetes was noted and compared.Results: In our study, among the 312 pregnant women, 88 (28%) developed GDM. Of these 74 Women (84%) with GDM had uric acid levels above 3.5 mg/dl and 14 women (15.9%) with GDM had uric acid levels below 3.5 mg/dl. Women with higher BMI showed high uric acid levels.Conclusions: Elevated serum uric acid in the first trimester has a significant correlation with development of GDM. In present study; the cut-off level of maternal serum uric acid of 3.5 mg/dl in the first trimester appears to have a good sensitivity and specificity in identifying those patients who are most likely to develop GDM later in pregnancy.

scholarly journals Failure to up-regulate VEGF165b in maternal plasma is a first trimester predictive marker for pre-eclampsia

2009 ◽  
Vol 116 (3) ◽  
pp. 265-272 ◽  
Author(s):  
Victoria L. Bills ◽  
Julia Varet ◽  
Ann Millar ◽  
Steven J. Harper ◽  
Peter W. Soothill ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Predictive Marker ◽  
First Trimester ◽  
Maternal Plasma ◽  
Related Condition ◽  
Increased Risk ◽  
Median Plasma ◽  
Endothelial Growth Factor ◽  
Plasma Marker ◽  
In Pregnancy

Pre-eclampsia is a pregnancy-related condition characterized by hypertension, proteinuria and endothelial dysfunction. VEGF165b, formed by alternative splicing of VEGF (vascular endothelial growth factor) pre-mRNA, inhibits VEGF165-mediated vasodilation and angiogenesis, but has not been quantified in pregnancy. ELISAs were used to measure means±S.E.M. plasma VEGF165b, sEng (soluble endoglin) and sFlt-1 (soluble fms-like tyrosine kinase-1). At 12 weeks of gestation, the plasma VEGF165b concentration was significantly up-regulated in plasma from women who maintained normal blood pressure throughout their pregnancy (normotensive group, 4.90±1.6 ng/ml; P<0.01, as determined using a Mann-Whitney U test) compared with non-pregnant women (0.40±0.22 ng/ml). In contrast, in patients who later developed pre-eclampsia, VEGF165b levels were lower than in the normotensive group (0.467±0.209 ng/ml), but were no greater than non-pregnant women. At term, plasma VEGF165b concentrations were greater than normal in both pre-eclamptic (3.75±2.24 ng/ml) and normotensive (10.58 ng/ml±3.74 ng/ml; P>0.1 compared with pre-eclampsia) pregnancies. Patients with a lower than median plasma VEGF165b at 12 weeks had elevated sFlt-1 and sEng pre-delivery. Concentrations of sFlt-1 (1.20±0.07 and 1.27±0.18 ng/ml) and sEng (4.4±0.18 and 4.1±0.5 ng/ml) were similar at 12 weeks of gestation in the normotensive and pre-eclamptic groups respectively. Plasma VEGF165b levels were elevated in pregnancy, but this increase is delayed in women that subsequently develop pre-eclampsia. In conclusion, low VEGF165b may therefore be a clinically useful first trimester plasma marker for increased risk of pre-eclampsia.

scholarly journals AB0747 MATERNAL AND FETAL OUTCOMES IN PREGNANT WOMEN WITH JUVENILE IDIOPATHIC ARTHRITIS: A SYSTEMATIC LITERATURE REVIEW

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1402.1-1402
Author(s):  
R. Pinheiro Torres ◽  
M. H. Fernandes Lourenco ◽  
A. Neto ◽  
F. Pimentel Dos Santos ◽  
I. Silva ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Literature Review ◽  
Pregnant Women ◽  
Systematic Literature Review ◽  
English Language ◽  
Placenta Previa ◽  
Bibliographic Databases ◽  
Fetal Outcomes ◽  
Term Birth ◽  
Increased Risk

Background:Juvenile idiopathic arthritis (JIA), one of the most common chronic diseases in children, can be classified in seven different categories according to its onset presentation. Concerns about pregnancy outcomes play a secondary role in disease approach. However, recent data showed an increased risk of pre-term birth in women with JIA instead the small patient samples analysed.Objectives:In this review, our aim is to describe the current available knowledge on JIA adverse, maternal and fetal, outcomes.Methods:A systematic literature review was conducted since January of 2000 until December 2020, by searching the PubMed and Embase bibliographic databases. The search was limited to articles in English language, presenting a comparator group (healthy individuals or patients without known auto-immune rheumatic diseases) and at least one clinical outcome of interest. Two independent reviewers screened the titles and abstracts followed by a full-text review to assess papers regarding their eligibility.Results:Ten observational studies out of 1560 references, fulfilled the inclusion criteria, of which, 9 were retrospective and 1 prospective. A total of 6.214 women with JIA (with 6.811 pregnancies) and 18.659.513 healthy controls (with 21.339.194 pregnancies) were included in this review.Concerning maternal outcomes, delivery by caesarian section (CS) was more frequent among JIA women (in 4 out of 6 studies). Pre-eclampsia was referred in 3 out of 6 studies and a higher risk of vaginal bleeding and placenta previa in one additional study. No study found an increased risk for gestational diabetes or hypertension in pregnant women with JIA.Regarding fetal outcomes, 8 studies revealed significantly increased of pre-term birth (only in first births in one study) but one study didn’t show any increased risk. Two studies showed a higher risk of small gestational age (SGA) and in another 2, increased risk for low birth weight (LBW). No evidence of increased risk of major congenital malformations.Conclusion:This systematic review suggests an increased risk for pre-eclampsia, preterm birth, delivery by CS, SGA and LBW, among pregnant women with JIA. Conclusions should be carefully interpreted, giving the heterogeneity of studied populations regarding demography, disease type, disease activity, and prescribed medication.Disclosure of Interests:None declared

scholarly journals Radioimmunoassay of plasma ouabain in healthy and pregnant individuals

2000 ◽  
Vol 165 (3) ◽  
pp. 669-677 ◽  
Author(s):  
O Vakkuri ◽  
SS Arnason ◽  
A Pouta ◽  
O Vuolteenaho ◽  
J Leppaluoto
Keyword(s):  
Pregnant Women ◽  
Human Plasma ◽  
High Performance ◽  
Chemical Nature ◽  
Solid Phase ◽  
Plasma Concentrations ◽  
First Trimester ◽  
Plasma Samples ◽  
Third Trimester ◽  
Endogenous Substances

Ouabain was recently isolated from human plasma, bovine hypothalamus and bovine adrenal in attempts to identify endogenous substances inhibiting the cell membrane sodium pump. A number of radioimmunoassays have been developed in order to study the clinical significance of ouabain. The results have been controversial with regard to the presence and chemical nature of plasma ouabain-like immunoreactivity. We have now measured ouabain in healthy and pregnant individuals using solid-phase extraction of plasma samples followed by a new radioimmunoassay with the extraordinary sensitivity of at least 2 fmol/tube (5 pmol/l). Plasma extracts, a previously isolated human plasma ouabain-like compound and bovine hypothalamic inhibitory factor displaced the tracer in parallel and eluted identically with ouabain in high-performance liquid chromatography. Plasma ouabain immunoreactivity was found to be much lower than reported previously: 12.6+/-1.3 pmol/l in healthy men (mean+/-s.e., n=20) and 9.4+/-0.7 pmol/l in women (n=14). In pregnant women (n=28) plasma ouabain concentration was 16.3+/-4.0 pmol/l during the first trimester, 18.8+/-4.3 pmol/l during the second trimester and 24.3+/-4.0 pmol/l during the third trimester (all P<0.01 compared with non-pregnant women). Plasma ouabain 3-5 days after the delivery was 13.6+/-1.1 pmol/l (n=10, P<0.05-0.01 compared with second and third trimesters). The pregnancy-related changes in the plasma concentrations of ouabain resembled those of cortisol. Therefore cortisol was measured from the same plasma samples and a significant positive correlation was found (r=0.512, P=0.006). The similar profiles of plasma ouabain and cortisol during pregnancy and their rapid decreases postpartum are consistent with the adrenal cortical origin of ouabain and also show that the secretions of these hormones are possibly under the control of same factors.

Women with high plasma levels of PBDE-47 are at increased risk of preterm birth

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Morgan R. Peltier ◽  
Michael J. Fassett ◽  
Yuko Arita ◽  
Vicki Y. Chiu ◽  
Jiaxiao M. Shi ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Los Angeles ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Plasma Concentrations ◽  
First Trimester ◽  
High Plasma ◽  
Thyroid Stimulating Hormone ◽  
Spontaneous Preterm Birth ◽  
Increased Risk

Abstract Objectives Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. Methods Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. Results We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. Conclusions These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.

scholarly journals Prenatal electrocardiogram testing and postpartum depression: A population-based cohort study

2021 ◽  
pp. 1753495X2110125
Author(s):  
Jonathan S Zipursky ◽  
Deva Thiruchelvam ◽  
Donald A Redelmeier
Keyword(s):  
Cohort Study ◽  
Postpartum Depression ◽  
Pregnant Women ◽  
Odds Ratio ◽  
Population Based ◽  
Relative Increase ◽  
Organic Disease ◽  
Increased Risk ◽  
Clinical Clue ◽  
In Pregnancy

Background Cardiovascular symptoms in pregnancy may be a clue to psychological distress. We examined whether electrocardiogram testing in pregnant women is associated with an increased risk of subsequent postpartum depression. Methods We conducted a population-based cohort study of pregnant women who delivered in Ontario, Canada comparing women who received a prenatal ECG to women who did not. Results In total, 3,238,218 women gave birth during the 25-year study period of whom 157,352 (5%) received an electrocardiogram during prenatal care. Receiving an electrocardiogram test was associated with a one-third relative increase in the odds of postpartum depression (odds ratio 1.34; 95% confidence interval 1.29–1.39, p < 0.001). Conclusion The association between prenatal electrocardiogram testing and postpartum depression suggests a possible link of organic disease with mental illness, and emphasizes that cardiovascular symptoms may be a clinical clue to the presence of an underlying mood disorder.

iGlarLixi: A Fixed-Ratio Combination of Insulin Glargine 100 U/mL and Lixisenatide for the Treatment of Type 2 Diabetes

2017 ◽  
Vol 51 (11) ◽  
pp. 990-999 ◽  
Author(s):  
Jennifer Goldman ◽  
Jennifer M. Trujillo
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Glargine ◽  
English Language ◽  
Data Extraction ◽  
Safety Data ◽  
Fixed Ratio ◽  
Postprandial Glucose ◽  
The United States ◽  
Glucagon Like Peptide 1

Objective: To review the safety and efficacy of iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide, a glucagon-like peptide-1 receptor agonist. Data Sources: A literature search of MEDLINE for all English-language primary articles through June 2016, using the terms LixiLan, iGlarLixi and insulin glargine and lixisenatide, and a search of abstracts presented at the 2016 Scientific Sessions of the American Diabetes Association were performed. Study Selection and Data Extraction: All studies assessing the efficacy and/or safety of iGlarLixi were evaluated. Data Synthesis: iGlarLixi has been approved in the United States for glycemic control in people with type 2 diabetes (T2D) inadequately controlled with basal insulin (<60 U/d) or lixisenatide. In clinical trials, iGlarLixi was associated with significantly greater reductions from baseline in glycated hemoglobin A1C (A1C) than iGlar or lixisenatide alone. Reductions in postprandial glucose were also greater with iGlarLixi than with iGlar or lixisenatide. iGlarLixi was weight neutral compared with the weight gain with iGlar and loss with lixisenatide alone, and there was no increase in hypoglycemia with iGlarLixi compared with iGlar despite the greater A1C reduction. Gastrointestinal events, frequently associated with lixisenatide, were less common with iGlarLixi. Potential drawbacks of iGlarLixi include reduced flexibility in dosing and the absence of long-term efficacy and safety data. Conclusions: iGlarLixi is a titratable fixed-ratio combination that shows improved efficacy and comparable or improved safety outcomes relative to its separate constituents, offering an alternative approach to intensification of therapy in T2D.

TSH/miR‐17‐5p/ZNF367 axis is related to spontaneous abortion in patients with TSH above 2.5 mIU/L

2021 ◽  
Author(s):  
Yang Yang ◽  
Jiashu Li ◽  
Yingying Zhou ◽  
Wen Dai ◽  
Weiping Teng ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Spontaneous Abortion ◽  
Biological Function ◽  
Zinc Finger Protein ◽  
First Trimester ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Chorionic Villi ◽  
Increased Risk

Elevated thyroid stimulating hormone (TSH) is associated with an increased risk of spontaneous abortion (SA); however, the associated mechanism remains unclear. This study aimed to investigate the expression of microRNAs (miRNAs) and pathogenesis in the chorionic villi of TSH > 2.5 mIU/L-related SA patients. The chorionic villi were collected from pregnant women in the first trimester with TSH > 2.5 mIU/L with or without SA, as well as TSH < 2.5 mIU/L with or without SA to determine the level of miRNA expression. Differentially expressed miRNAs were confirmed by qRT-PCR in a total of 92 subjects. Cell counting kit-8 (CCK8), wound healing, transwell assays, and Western blotting were used to measure cellular biological functions and related protein in HTR-8/SVneo cells. The potential mechanisms were determined using a Luciferase reporter assay and rescue experiment. Compared with normal pregnant women, miR-17-5p was decreased and zinc finger protein 367 (ZNF367) was upregulated in the chorionic villi of TSH > 2.5 mIU/L-related SA patients. Using HTR-8/SVneo cells, we demonstrated that elevated TSH inhibited miR-17-5p expression, as well as trophoblast migration and invasion. The overexpression of miR-17-5p targeted and inhibited ZNF367 expression promoting the biological function of trophoblasts. Further studies confirmed that ZNF367 interference partially reversed the biological function of the miR-17-5p inhibitor on HTR-8/SVneo cells. Taken together, our results showed that miR-17-5p promoted biological function of trophoblasts by suppressing ZNF367.

scholarly journals Prevalence and aetiologies of anaemia among first trimester pregnant women in Sri Lanka; the need for revisiting the current control strategies

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Gayani Shashikala Amarasinghe ◽  
Thilini Chanchala Agampodi ◽  
Vasana Mendis ◽  
Krishanthi Malawanage ◽  
Chamila Kappagoda ◽  
...  
Keyword(s):  
Public Health ◽  
Iron Deficiency ◽  
Pregnant Women ◽  
Blood Count ◽  
First Trimester ◽  
Full Blood Count ◽  
Red Cell ◽  
Middle Income ◽  
Anaemia In Pregnancy ◽  
In Pregnancy

Abstract Background The Sustainable development goals, which focus strongly on equity, aim to end all forms of malnutrition by 2030. However, a significant cause of intergenerational transfer of malnutrition, anaemia in pregnancy, is still a challenge. It is especially so in the low- and middle-income settings where possible context-specific aetiologies leading to anaemia have been poorly explored. This study explores the prevalence of etiological factors significantly contributing to anaemia in pregnancy in Sri Lanka, a lower-middle-income country with a high prevalence of malnutrition albeit robust public health infrastructure. Methods All first-trimester pregnant women registered in the public maternal care programme in the Anuradhapura district from July to September 2019 were invited to participate in Rajarata Pregnancy Cohort (RaPCo). After a full blood count analysis, high-performance liquid chromatography, peripheral blood film examination, serum B12 and folate levels were performed in anaemic participants, guided by an algorithm based on the red cell indices in the full blood count. In addition, serum ferritin was tested in a random subsample of 213 participants. Anaemic women in this subsample underwent B12 and folate testing. Results Among 3127 participants, 14.4% (95%CI 13.2–15.7, n = 451) were anaemic. Haemoglobin ranged between 7.4 to 19.6 g/dl. 331(10.6%) had mild anaemia. Haemoglobin ≥13 g/dl was observed in 39(12.7%). Microcytic, normochromic-normocytic, hypochromic-normocytic and macrocytic anaemia was observed in 243(54%), 114(25.3%), 80(17.8%) and two (0.4%) of full blood counts in anaemic women, respectively. Microcytic anaemia with a red cell count ≥5 * 106 /μl demonstrated a 100% positive predictive value for minor haemoglobinopathies. Minor hemoglobinopathies were present in at least 23.3%(n = 105) of anaemic pregnant women. Prevalence of iron deficiency, B12 deficiency and Southeast Asian ovalocytosis among the anaemic was 41.9% (95%CI 26.4–59.2), 23.8% (95%CI 10.6–45.1) and 0.9% (95%CI 0.3–2.3%), respectively. Folate deficiency was not observed. Conclusion Even though iron deficiency remains the primary cause, minor hemoglobinopathies, B 12 deficiency and other aetiologies substantially contribute to anaemia in pregnancy in this study population. Public health interventions, including screening for minor hemoglobinopathies and multiple micronutrient supplementation in pregnancy, should be considered in the national programme for areas where these problems have been identified.

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