scholarly journals Modulation of Wolframin Expression in Human Placenta during Pregnancy: Comparison among Physiological and Pathological States

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Angela Lucariello ◽  
Angelica Perna ◽  
Carmine Sellitto ◽  
Alfonso Baldi ◽  
Alessandro Iannaccone ◽  
...  
Keyword(s):  
Human Placenta ◽  
Autosomal Recessive Disorder ◽  
Cell Loss ◽  
Wolfram Syndrome ◽  
First Trimester ◽  
Third Trimester ◽  
Gene Encoding ◽  
Cytotrophoblast Cell ◽  
The Third ◽  
Normal Placenta

TheWFS1gene, encoding a transmembrane glycoprotein of the endoplasmic reticulum called wolframin, is mutated in Wolfram syndrome, an autosomal recessive disorder defined by the association of diabetes mellitus, optic atrophy, and further organ abnormalities. Disruption of theWFS1gene in mice causes progressiveβ-cell loss in the pancreas and impaired stimulus-secretion coupling in insulin secretion. However, little is known about the physiological functions of this protein. We investigated the immunohistochemical expression of wolframin in human placenta throughout pregnancy in normal women and diabetic pregnant women. In normal placenta, there was a modulation of wolframin throughout pregnancy with a strong level of expression during the first trimester and a moderate level in the third trimester of gestation. In diabetic women, wolframin expression was strongly reduced in the third trimester of gestation. The pattern of expression of wolframin in normal placenta suggests that this protein may be required to sustain normal rates of cytotrophoblast cell proliferation during the first trimester of gestation. The decrease in wolframin expression in diabetic placenta suggests that this protein may participate in maintaining the physiologic glucose homeostasis in this organ.

Correlations Between the Values of Maternal Glycemia from the Last Trimester of Pregnancy and Fetal Birth Weight

2013 ◽  
Vol 20 (3) ◽  
pp. 259-265
Author(s):  
Monica Vereş ◽  
Aurel Babeş ◽  
Szidonia Lacziko
Keyword(s):  
First Trimester ◽  
Mean Value ◽  
Fetal Macrosomia ◽  
Entire Group ◽  
Third Trimester ◽  
The Third ◽  
Group I ◽  
Fetal Birth Weight ◽  
First Trimester Of Pregnancy ◽  
The Mean

Abstract Background and aims: Gestational diabetes represents a form of diabetes diagnosed during pregnancy that is not clearly overt diabetes. In the last trimester of gestation the growth of fetoplacental unit takes place, thus maternal hyperglycemia will determine an increased transplacental passage, hyperinsulinemia and fetal macrosomia. The aim of our study was that o analyzing the effect of maternal glycemia from the last trimester of pregnancy over fetal weight. Material and method: We run an observational study on a group of 46 pregnant women taken into evidence from the first trimester of pregnancy, separated in two groups according to blood glucose determined in the third trimester (before birth): group I normoglycemic and group II with hyperglycemia (>92mg/dl). Results: The mean value of third trimester glycemia for the entire group was of 87.13±22.03. The mean value of the glycemia determined in the third trimester of pregnancy was higher in the second group (109.17 mg/dl) in comparison to the first group (74.,21 mg/dl). The ROC curve for third trimester glycemia as fetal macrosomia appreciation test has an AUC of 0.517. Conclusions: Glycemia determined in the last trimester of pregnancy cannot be used alone as the predictive factor for fetal macrosomia.

scholarly journals Novel mutations in the WFS1 gene are associated with Wolfram syndrome and systemic inflammation

2021 ◽  
Author(s):  
Eleonora Panfili ◽  
Giada Mondanelli ◽  
Ciriana Orabona ◽  
Maria L Belladonna ◽  
Marco Gargaro ◽  
...  
Keyword(s):  
Er Stress ◽  
Mononuclear Cells ◽  
Autosomal Recessive Disorder ◽  
Wolfram Syndrome ◽  
Therapeutic Interventions ◽  
T Helper 17 ◽  
Gene Encoding ◽  
Peripheral Blood Mononuclear ◽  
Inflammatory State ◽  
Wfs1 Gene

Abstract Mutations in the WFS1 gene, encoding wolframin (WFS1), cause endoplasmic reticulum (ER) stress and are associated with a rare autosomal-recessive disorder known as Wolfram syndrome (WS). WS is clinically characterized by childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus and neurological signs. We identified two novel WFS1 mutations in a patient with WS, namely, c.316-1G > A (in intron 3) and c.757A > T (in exon 7). Both mutations, located in the N-terminal region of the protein, were predicted to generate a truncated and inactive form of WFS1. We found that although the WFS1 protein was not expressed in peripheral blood mononuclear cells (PBMCs) of the proband, no constitutive ER stress activation could be detected in those cells. In contrast, WS proband’s PBMCs produced very high levels of proinflammatory cytokines (i.e. TNF-α, IL-1β, and IL-6) in the absence of any stimulus. WFS1 silencing in PBMCs from control subjects by means of small RNA interference also induced a pronounced proinflammatory cytokine profile. The same cytokines were also significantly higher in sera from the WS patient as compared to matched healthy controls. Moreover, the chronic inflammatory state was associated with a dominance of proinflammatory T helper 17 (Th17)-type cells over regulatory T (Treg) lymphocytes in the WS PBMCs. The identification of a state of systemic chronic inflammation associated with WFS1 deficiency may pave the way to innovative and personalized therapeutic interventions in WS.

scholarly journals Infliximab clearance decreases in the second and third trimesters of pregnancy in inflammatory bowel disease

2020 ◽  
pp. 205064062096461
Author(s):  
Ana-Marija Grišić ◽  
Maria Dorn-Rasmussen ◽  
Bella Ungar ◽  
Jørn Brynskov ◽  
Johan F K F Ilvemark ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
First Trimester ◽  
Interquartile Range ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Second Trimester ◽  
Third Trimester ◽  
The Third ◽  
Inflammatory Bowel

Background Infliximab therapy during pregnancy in inflammatory bowel disease is challenged by a dilemma between maintaining adequate maternal disease control while minimizing fetal infliximab exposure. We investigated the effects of pregnancy on infliximab pharmacokinetics. Methods The study population comprised 23 retrospectively identified pregnancies. Patients with inflammatory bowel disease were generally in clinical remission at pregnancy conception (74%) and received steady infliximab maintenance therapy (5 mg/kg q8w n = 17; q6w n = 4; q10w n = 1; 10 mg/kg q8w n = 1). Trough blood samples had been obtained in the same patients prior to pregnancy ( n = 119), the first trimester ( n = 16), second trimester ( n = 18), third trimester ( n = 7), and post-pregnancy ( n = 12). Data were analyzed using nonlinear mixed-effects population pharmacokinetic modelling. Results Dose-normalized infliximab concentrations were significantly higher during the second trimester (median 15 µg/mL/kg, interquartile range 10–21) compared to pre-pregnancy (7, 2–12; p = 0.003), the first trimester (9, 1–12; p = 0.04), or post-pregnancy (6, interquartile range 3–11; p > 0.05) in patients with inflammatory bowel disease. Similar trends were observed in the third trimester (13, 7–36; p > 0.05). A one-compartment model with linear elimination described the pharmacokinetics of infliximab (volume of distribution = 18.2 L; clearance 0.61 L/day). Maternal infliximab exposure was influenced by the second and third trimester of pregnancy and anti-infliximab antibodies, and not by pregnancy-imposed physiological changes in, for example, body weight or albumin. Infliximab clearance decreased significantly during the second and third trimesters by up to 15% as compared to pre- and post-pregnancy and the first trimester. The increased maternal infliximab exposure was weakly associated with lowered clinical disease activity. Pharmacokinetic model simulations of virtual patients indicated the increased maternal infliximab trough concentrations imposed by pregnancy will not completely counteract the decrease in infliximab concentration if therapy is paused in the third trimester. Conclusion Infliximab clearance decreases significantly in the second and third trimesters, leading to increasing maternal infliximab concentrations in any given regimen. Maternal infliximab levels may thus be maintained as constant in a de-intensified regimen by therapeutic drug monitoring guidance in inflammatory bowel disease.

scholarly journals The Effect of Preserving Pregnancy in Cervical Cancer Diagnosed During Pregnancy: A Retrospective Study

2021 ◽  
Author(s):  
Zuoxi He ◽  
Chuan Xie ◽  
Xiaorong Qi ◽  
Zhengjun Hu ◽  
Yuedong He
Keyword(s):  
Cervical Cancer ◽  
Rare Event ◽  
Oncologic Outcome ◽  
First Trimester ◽  
Second Trimester ◽  
Third Trimester ◽  
Delayed Treatment ◽  
The Third ◽  
Survival Difference ◽  
Estimated Blood Loss

Abstract ObjectiveCervical cancer diagnosed during pregnancy is a rare event, and data regarding efficacy of cancer treatment during pregnancy is limited. This study aimed to assess the safety of continuation of the pregnancy for mother and fetus when concomitantly diagnosed with cervical cancer.MethodsThis study retrospectively analyzed all cervical cancer patients diagnosed while pregnant or immediately postpartum, inclusive from Jan 2010 to June 2019 at our institute. Patient clinical details and follow-up were obtained from hospital records. ResultsThe study comprised 40 patients with clinical cancer stages of ⅠA1 (1/40, 2.5%); ⅠB1 (15/40, 37.5%); IB2 (10/40, 25%); ⅡA (12/40, 30%); and ⅡB (2/40, 5%). There were 38 patients diagnosed during pregnancy, and 2 diagnosed in the postpartum period. Of the 38 patients, 17 were diagnosed in the first trimester, 13 in the second trimester, and 8 in the third trimester. Ten of 38 patients (26.3%) continued their pregnancy after learning of their diagnosis; 7 (70%) in the third trimester and 3 (30%) in the second trimester. The mean time from diagnosis to surgery in the patients who continued their pregnancy was 52.7 days, which was statistically significantly greater than the termination of pregnancy group (52.7 vs 16.3 days, P < 0.01). Notably, there was no survival difference between the 2 groups (100% vs 90.91%, P =0.54), and none of the pregnant women who ultimately died had delayed treatment due to pregnancy. Similarly, the surgical estimated blood loss and operative duration comparing the 2 groups were not significantly different. ConclusionsIn the present study, the gestational age of pregnancy at the time of initial diagnosis of cervical cancer was an important determinant in the disease management. Continuation of the pregnancy when diagnosed with cervical cancer did not affect the oncologic outcome of the mother nor increase either surgical or obstetric complications. Additionally, the use of neoadjuvant chemotherapy did not threaten the health of the fetus. These results may be useful in counseling patients facing the diagnosis of cervical cancer during pregnancy.

Androgen secretion in women with threatened miscarriage

2020 ◽  
Vol 19 (5) ◽  
pp. 22-28
Author(s):  
М.М. Amiraslanova ◽  
◽  
I.V. Kuznetsova ◽  
E.P. Gitel ◽  
◽  
...  
Keyword(s):  
Pregnancy Outcomes ◽  
First Trimester ◽  
Total Testosterone ◽  
Third Trimester ◽  
Group Iii ◽  
The Third ◽  
Threatened Miscarriage ◽  
Group I ◽  
Androgen Secretion ◽  
Group Ii

Objective. To assess androgen secretion and its possible effect on pregnancy in women with threatened miscarriage in the first trimester. Patients and methods. This prospective observational study included 120 pregnant women divided into four groups. Group I comprised 32 patients with threatened miscarriage and hyperandrogenism who received corticosteroids; Group II was composed of 28 patients with threatened miscarriage and hyperandrogenism who did not receive corticosteroids; Group III included 30 patients with threatened miscarriage and no hyperandrogenism; and Group IV comprised 30 women with normal pregnancy. Serum levels of dehydroepiandrosterone sulfate (DHEA-S), 17-hydroxyprogesterone (17-OHP), and total testosterone were measured on the following weeks of gestation: 5–8, 9–12, 13–18, 19–24, and 25–32. We also evaluated clinical outcomes of pregnancy. Results. We observed no significant differences in 17-ОНР and DHEA-S secretion between women from Group III and controls. Patients from Group II demonstrated higher hormone levels than controls; however, their dynamics of 17-ОНР and testosterone secretion was similar to that in women without hyperandrogenism, so their DHEA-S levels decreased and reached control values by the third trimester. Corticosteroids reduced 17-ONR secretion in the second and third trimesters and DHEA-S secretion in the third trimester. Women receiving corticosteroids demonstrated the poorest clinical pregnancy outcomes. Conclusion. Hyperandrogenism should be considered as one of the risk factors for poor pregnancy outcomes. Administration of corticosteroids to reduce androgen levels impairs normal dynamics of their secretion, does not improve pregnancy outcomes, and is potentially harmful; therefore, these drugs should not be used for such purposes. Key words: pregnancy, hyperandrogenism, corticosteroid therapy, pregnancy outcomes, pregnancy loss, androgen secretion, threatened miscarriage

scholarly journals Influence of quality of sleep in the first trimester on blood pressure in the third trimester in primipara women

2019 ◽  
Vol 28 (5) ◽  
pp. 345-355 ◽  
Author(s):  
Kimie Okada ◽  
Izumi Saito ◽  
Chihiro Katada ◽  
Takeshi Tsujino
Keyword(s):  
Blood Pressure ◽  
First Trimester ◽  
Quality Of Sleep ◽  
Third Trimester ◽  
The Third

Sequelae of Congenital Cytomegalovirus Following Maternal Primary Infections Are Limited to Those Acquired in the First Trimester of Pregnancy

2018 ◽  
Vol 69 (9) ◽  
pp. 1526-1532 ◽  
Author(s):  
Valentine Faure-Bardon ◽  
Jean-François Magny ◽  
Marine Parodi ◽  
Sophie Couderc ◽  
Patricia Garcia ◽  
...  
Keyword(s):  
Primary Infection ◽  
Accurate Determination ◽  
First Trimester ◽  
Maternal Infection ◽  
Third Trimester ◽  
The Third ◽  
Neurologic Sequelae ◽  
Early Fetal Period ◽  
Case Outcome

Abstract Background The known relationship between the gestational age at maternal primary infection an the outcome of congenital CMV is based on small, retrospective studies conducted between 1980 and 2011. They reported that 32% and 15% of cases had sequelae following a maternal primary infection in the first and second or the third trimester, respectively. We aimed to revisit this relationship prospectively between 2011 and 2017, using accurate virological tools. Methods We collected data on women with a primary infection and an infected child aged at least 1 year at the time of analysis. An accurate determination of the timing of the primary infection was based upon serial measurements of immunoglobulin (Ig) M and IgG and on IgG avidity in sera collected at each trimester. The case outcome was assessed according to a structured follow-up between birth and 48 months. Results We included 255 women and their 260 fetuses/neonates. The dating of the maternal infection was prospective in 86% of cases and retrospective in 14%. At a median follow-up of 24 months, the proportion of sensorineural hearing loss and/or neurologic sequelae were 32.4% (95% confidence interval [CI] 23.72–42.09) after a maternal primary infection in the first trimester, 0 (95% CI 0–6.49) after an infection in the second trimester, and 0 (95% CI 0–11.95) after an infection in the third trimester (P < .0001). Conclusions These results suggest that a cytomegalovirus infection can be severe only when the virus hits the fetus in the embryonic or early fetal period. Recent guidelines recommend auditory follow-ups for at least 5 years for all infected children. This raises parental anxiety and generates significant costs. We suggest that auditory and specialized neurologic follow-ups may be recommended only in cases of a maternal infection in the first trimester.

Gestation specific reference intervals for thyroid function tests in pregnancy

2016 ◽  
Vol 54 (8) ◽  
Author(s):  
Süleyman Akarsu ◽  
Filiz Akbiyik ◽  
Eda Karaismailoglu ◽  
Zeliha Gunnur Dikmen
Keyword(s):  
Pregnant Women ◽  
Thyroid Function ◽  
First Trimester ◽  
Reference Intervals ◽  
Specific Reference ◽  
Thyroid Function Tests ◽  
Second Trimester ◽  
Third Trimester ◽  
The Third ◽  
Function Tests

AbstractThyroid function tests are frequently assessed during pregnancy to evaluate thyroid dysfunction or to monitor pre-existing thyroid disease. However, using non-pregnant reference intervals can lead to misclassification. International guidelines recommended that institutions should calculate their own pregnancy-specific reference intervals for free thyroxine (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH). The objective of this study is to establish gestation-specific reference intervals (GRIs) for thyroid function tests in pregnant Turkish women and to compare these with the age-matched non-pregnant women.Serum samples were collected from 220 non-pregnant women (age: 18–48), and 2460 pregnant women (age: 18–45) with 945 (39%) in the first trimester, 1120 (45%) in the second trimester, and 395 (16%) in the third trimester. TSH, FT4 and FT3 were measured using the Abbott Architect i2000SR analyzer.GRIs of TSH, FT4 and FT3 for first trimester pregnancies were 0.49–2.33 mIU/L, 10.30–18.11 pmol/L and 3.80–5.81 pmol/L, respectively. GRIs for second trimester pregnancies were 0.51–3.44 mIU/L, 10.30–18.15 pmol/L and 3.69–5.90 pmol/L. GRIs for third trimester pregnancies were 0.58–4.31 mIU/L, 10.30–17.89 pmol/L and 3.67–5.81 pmol/L. GRIs for TSH, FT4 and FT3 were different from non-pregnant normal reference intervals.TSH levels showed an increasing trend from the first trimester to the third trimester, whereas both FT4 and FT3 levels were uniform throughout gestation. GRIs may help in the diagnosis and appropriate management of thyroid dysfunction during pregnancy which will prevent both maternal and fetal complications.

HtrA3 Isoform–Specific ELISAs for Early Detection of Preeclampsia

2016 ◽  
Vol 23 (10) ◽  
pp. 1092-1099 ◽  
Author(s):  
Yao Wang ◽  
Ying Li ◽  
Jonathan Hyett ◽  
Fabricio da Silva Costa ◽  
Guiying Nie
Keyword(s):  
Early Detection ◽  
Early Onset ◽  
Late Onset ◽  
Pdz Domain ◽  
First Trimester ◽  
Potential Utility ◽  
Third Trimester ◽  
The Third ◽  
Early Onset Preeclampsia ◽  
Singleton Pregnancies

Preeclampsia is a serious disorder of human pregnancy occurring after 20 weeks of gestation. It can be divided into subtypes of early onset (<34 weeks of gestation) and late onset (>34 weeks). Presymptomatic detection to identify those at high risk is important for managing this disease. HtrA3, a serine protease with high expression in the developing placenta, exists in long (HtrA3-L) and short (HtrA3-S) isoforms. They are identical, except HtrA3-S lacks the C-terminal PDZ domain. We have previously shown by Western blot analysis that serum HtrA3 levels at the end of the first trimester are significantly higher in women who later develop preeclampsia than in controls. In this study, using highly specific HtrA3 monoclonal antibodies, we established and fully validated two enzyme-linked immunosorbent assays to detect both HtrA3 isoforms together (HtrA3-T) and HtrA3-L alone in the human serum. We then determined serum HtrA3 at 11 to 13 weeks of gestation in a cohort of singleton pregnancies that proceeded without complications or developed preeclampsia in the third trimester. Compared with controls, those who developed late-onset preeclampsia had significantly higher levels of HtrA3-L, whereas those who developed early-onset preeclampsia had significantly lower ratios of HtrA3-L/HtrA3-T. These data support a potential utility of these HtrA3 ELISAs for early detection of preeclampsia.

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