Prevalence and Risk Factors of Gestational Diabetes in Twin Pregnancies: Population Based Study

Objective: To assess the prevalence and risk factors of gestational diabetes (GDM) in twin compared with singleton pregnancies. Methods: Population-based study using CDC birth data from 2016-2020. Higher order pregnancies and pre-pregnancy diabetes were excluded. A Chi-square test of independence was performed to identify significant factors associated with GDM in twin versus singleton pregnancies and within each group independently. Multivariable regression analyses were performed first to assess risk factors that are significantly associated with GDM in twins and second to assess the risk of GDM in twin compared with singletons, adjusted for the significant risk factors. P value<0.01 was considered statistically significant Results: Total of 18,173,365 singleton and 611,043 twin pregnancies were included during the study period. Following the regression model, maternal age≥30 years, nulliparous, IVF, chronic hypertension, Hispanic and Non-Hispanic (NH) Asian, foreign-born, overweight and obesity class I/II/II remained significantly associated with GDM in twins. However, maternal age<25 years, NH Black, and W.I.C program reduced that risk. Factors that more than doubled the risk in twins were maternal age≥40 years (OR 2.06 (1.97 – 2.14), P<0.001), NH Asian (OR 2.12 (2.04 – 2.20), P<0.001), and obesity class I, II, and III (OR: 2.22 (2.16 – 2.29), P<0.001, OR:3.01 (2.92 – 3.11), P<0.001, OR: 3.80 (3.67 – 3.93), p<0.001, respectively). Following adjustment for all the significant risk factors, twin pregnancy remained significantly associated with increasing the risk of GDM in twin compared to singleton pregnancies (OR 1.22 (1.21 – 1.23), P<0.001). Conclusion: Of the significant risk factors, maternal age≥40 years, NH Asian, and obesity class I, II, and III more than doubled the risk of GDM in twins. Regardless of maternal demographics, obstetric history, and endocrine factors, twin pregnancy remained significantly associated with GDM compared to singleton pregnancies. These factors can be used in risk prediction models to better counsel and manage twin pregnancies

Clinical Study Maternal Hypotension during Fetoscopic Surgery: Incidence and Its Impact on Fetal Survival Outcomes

In this retrospective cohort study, we aimed to determine the incidence of intraoperative maternal hypotension during fetoscopic surgery for twin-twin transfusion syndrome (TTTS) and to evaluate the impact of intraoperative hypotension on fetal survival. A total of 328 TTTS patients with recipient twin cardiomyopathy who underwent fetoscopic surgery under epidural anesthesia were included. The exposure of interest was maternal medical therapy with nifedipine for the treatment of fetal cardiomyopathy. We found that intraoperative hypotension occurred in 53.4% (175/328 patients). There was no statistically significant difference in incidence of hypotension between nifedipine exposure and nonexposure groups (54.8% versus 50.8%, = 0.479). However, the nifedipine exposure group received a statistically significant higher dose of phenylephrine (7.04 ± 6.38 mcg/kg versus 4.70 ± 4.14 mcg/kg, = 0.018) and higher doses of other vasopressor, as counted by number of treatments (6.06 ± 4.58 versus 4.96 ± 3.42, = 0.022). There were no statistically significant differences in acute fetal survival rate (within 5 days) and fetal survival rate at birth between hypotensive and nonhypotensive patients. We concluded that preoperative exposure to nifedipine resulted in increased intraoperative maternal vasopressor requirement during fetoscopic surgery under epidural anesthesia. In patients who had intraoperative maternal hypotension, there was no correlation between the presence of maternal hypotension and postoperative fetal survival

Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms.

Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor -1 (hIGF-1) in the placenta corrects fetal weight deficits in mouse, rat, and rabbit models of intrauterine growth restriction without changes in placental weight. The underlying mechanisms of this effect have not been elucidated. To investigate the effect of intra-placental IGF-1 over-expression on placental function we examined glucose transporter expression and localization in both a mouse model of IUGR and a model of human trophoblast, the BeWo Choriocarcinoma cell line.At gestational day 18, animals were divided into four groups; sham-operated controls, uterine artery branch ligation (UABL), UABL+Ad-hIGF-1 (10(8) PFU), UABL+Ad-LacZ (10(8) PFU). At gestational day 20, pups and placentas were harvested by C-section. For human studies, BeWo choriocarcinoma cells were grown in F12 complete medium +10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 hours. MOIs of 10∶1 and 100∶1 were utilized. The RNA, protein expression and localization of glucose transporters GLUT1, 3, 8, and 9 were analyzed by RT-PCR, Western blot and immunohistochemistry.In both the mouse placenta and BeWo, GLUT1 regulation was linked to altered protein localization. GLUT3, localized to the mouse fetal endothelial cells, was reduced in placental insufficiency but maintained with Ad-I GF-1 treatment. Interestingly, GLUT8 expression was reduced in the UABL placenta but up-regulated following Ad-IGF-1 in both mouse and human systems. GLUT9 expression in the mouse was increased by Ad-IGF-1 but this was not reflected in the BeWo, where Ad-IGF-1 caused moderate membrane relocalization.Enhanced GLUT isoform transporter expression and relocalization to the membrane may be an important mechanism in Ad-hIGF-1mediated correction of placental insufficiency

Sacral Neuromodulation for Non-Obstructive Urinary Retention: A Meta-Analysis

Objective. The object of this study is to systematically review the literature regarding the efficacy of sacral neuromodulation (InterStim®) for treatment of non-obstructive urinary retention. Methods. Eligible studies were selected through an electronic literature search of PubMed, Cochrane Collaboration, EMBASE, Web of Science and Scopus databases from January 1980 to August 2008. Two investigators independently reviewed all studies to assess methodological quality and inclusion criteria. Eligible studies evaluated sacral neuromodulation using implanted generators with permanent lead placement for treating non-obstructive urinary retention. The primary outcomes assessed were the change in pre- and postoperative post-void residual and voided volume. Exclusion criteria were neurogenic etiology (i.e. spinal cord injury) for urinary retention and non-English studies. The lead authors of all selected studies were contacted to identify ongoing or unpublished research, as was Medtronic, Inc. (Minneapolis, MN). Data were extracted from the selected studies and analyzed using RevMan 5 (Review Manager, Cochrane Collaboration, 2008). The mean difference with a 95% confidence interval was the effect of interest. Results. A total of 14 articles met all inclusion criteria for the systematic review. This included one randomized control trial (RCT) and thirteen observational studies. Outcome data was available from a total of 7 studies and used in the final analysis. After implantation, the mean difference in post-void residual decreased 236ml (95% CI: 219-253, p \u3c 0.00001) and voided volume increased by 299ml (95% CI: 280-318, p \u3c 0.00001). The randomized control trial alone (n = 51) showed a mean decrease in postvoid residual volume in the implanted group compared to control of 270ml (95% CI: 180-360, p \u3c 0.00001) and a mean increase in voided volume of 104 ml (95% CI: 55-152, p \u3c 0.0002). Conclusion. Based on the available literature, sacral neuromodulation is an effective therapy for treatment of nonobstructive urinary retention. Non-obstructive urinary retention is caused either by bladder dysfunction or from urethral obstruction. Bladder dysfunction may be caused by a weak or acontractile bladder muscle. The etiology of this disorder may be due to a myogenic, neurogenic or psychogenic origin. The multifactorial nature of this disorder contributes to the difficulty in finding an effective treatment modality. Traditional management has included pharmacotherapy and urethral dilation neither of which has been particularly successful. Individuals suffering from this disorder often need to learn how to perform clean 22 intermittent self-catheterization (CISC). Furthermore, individuals who cannot perform CISC due to physical limitations require an indwelling catheter. Although the mechanism of sacral neuromodulation was and remains unclear, the FDA approved its use for non-obstructive urinary retention in 1999

GLUT8 mRNA expression is significantly increased following exposure of BeWo cells to Ad-IGF-1 at an MOI of 100∶1 for 48 hours.

<p>ANOVA, Tukeys posthoc test ***p<0.005, n = 6 replicates</p

GLUT expression levels in BeWo cells.

<p>A:Representative Western blots of GLUT1, 3, and 8 in BeWo cells treated with control media (C), Ad-hIGF-1 MOI 10∶1 (10), Ad-hIGF-1 MOI 100∶1 (100) for 48 hours. B: Summary of GLUT1, 3, 8 protein expression. ANOVA, Tukeys posthoc test, *p<0.05, ** p<0.01, n>4 replicates for each treatment.</p

Summary of GLUT1, 3, 8 and 9 mRNA expression in control, UABL, Ad-hIGF-1 and Ad-LacZ treated mouse placentas.

<p>ANOVA, Post hoc Tukeys test * p<0.05, n>3 for each treatment</p

Representative micrographs of GLUT1 (A,B,C), GLUT3 (D,E,F), GLUT8 (G,H,I), GLUT9a (J,K,L) and GLUT9b (M,N,O) in mouse placental labyrinth in the 3 treatment groups, Sham, UABL and Ad-hIGF-1 respectively.

<p>100× magnification. ST identifies syncytiotrophoblast, * identifies a fetal villous vessel, # identifies a maternal blood sinus. Micrographs are representative of 3 biological replicates for each treatment group.</p