Jose L. Bartha

Inflammatory cytokines in intrauterine growth retardation

Background.  To evaluate maternal serum levels of two inflammatory cytokines in women with intrauterine growth retardation (IUGR), while studying separately women with or without placental insufficiency.

Early diagnosis of gestational diabetes mellitus and prevention of diabetes-related complications

OBJECTIVE [corrected] To test the hypothesis that an early diagnosis of gestational diabetes mellitus (GDM) could avoid some diabetes-related complications. STUDY DESIGN We compared the rates of pregnancy complications commonly related to diabetes between 189 (later screening group) and 235 (earlier screening group) women with GDM diagnosed before and after adding an universal glucose tolerance screening performed in the first antenatal visit to the traditional screening performed at 24-28 weeks of gestation. RESULTS Women in the later screening group were likely to have hydramnios (12.7 versus 2.1%, P<0.0001) and preterm deliveries (11.8 versus 5.5%; P=0.03). All cases of preterm premature rupture of membranes and fetal anomalies took place in the later screening group (P=0.03, P=0.007, respectively). Statistical analysis was performed using the Students t-test, Mann-Whitneys U-test, Fishers exact test and chi2-test. Statistical significance was set at 95% level (P<0.05). CONCLUSIONS Early glucose tolerance screening could avoid some diabetes-related complications in women with gestational diabetes. However, further studies are needed to know if it should be done in all pregnant women or only in those with a high risk of developing diabetes.

Bishop score and transvaginal ultrasound for preinduction cervical assessment: a randomized clinical trial

To compare transvaginal ultrasound with the Bishop score in assessment of cervical ripening for choice of induction agent.

Sex hormone-binding globulin in gestational diabetes

Background. Insulin is an important regulator of serum sex hormone‐binding globulin ( SHBG) concentration which works by inhibiting its production in hepatocytes. Low SHBG level is associated with increased insulin resistance and hyperinsulinemia. Our purpose was to compare maternal serum SHBG level between normal and gestational diabetic pregnant women and to study the relationships between SHBG, SHBG/insulin and SHBG/glucose ratio and several endocrine, metabolic and clinical parameters.

Factors influencing pregnancy outcome in women with type 2 versus type 1 diabetes mellitus

Aim. To compare pregnancy outcome and factors related to adverse perinatal outcome in women with type 1 versus type 2 diabetes mellitus (DM). Material and methods. Multicentre retrospective study. Some 404 women were studied, 257 with type 1 DM and 147 with type 2 DM. Main outcome measures were rates of prematurity, macrosomia, instrumental deliveries, congenital malformations, need for neonatal intensive care unit (NICU), and perinatal mortality. Results. There were no significant differences in pregnancy outcome between women with type 1 and type 2 DM, except for an increased rate of instrumental deliveries in women with type 1 DM. In these women, duration of diabetes was a significant predictor of caesarean delivery (OR =1.06 (1.01–1.12); p = 0.02). Chronic hypertension was positively related to prematurity (p = 0.02), and proved to be a significant predictor of birth weight lower than 2,500 g (OR =3.54 (1.4–12.49); p = 0.043) and perinatal mortality (OR =10.6 (1.15–117.6); p = 0.04). In women with type 2 DM, third trimester higher glycosylated haemoglobin was related to both prematurity (OR 4.9 (1.7–14.4; p = 0.004) and low birth weight. Macrosomia was a significant risk factor for caesarean section. First trimester glycosylated haemoglobin was related to congenital malformations and proved to be a significant predictor of perinatal mortality (OR =2.4 (1.02–5.74); p = 0.04). Conclusions. Duration of DM and chronic hypertension were the most influential factors related to adverse perinatal outcomes in women with type 1 DM, and poor metabolic control and macrosomia in women with type 2 DM.

High-glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta

Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides.

The relationships between leptin and inflammatory cytokines in women with pre‐eclampsia

Objective To compare maternal serum leptin concentration in women with pre‐eclampsia and women with normal pregnancy, and to evaluate the relationships between leptin and several inflammatory cytokines.

Oral misoprostol and intracervical dinoprostone for cervical ripening and labor induction: a randomized comparison

Objective To compare efficacy, safety, and tolerance of oral misoprostol with intracervical dinoprostone for cervical ripening and labor induction. Methods Two hundred women were randomized to receive single doses of oral misoprostol 200 μg or 0.5 mg of dinoprostone intracervically every 6 hours for a maximum four doses. Results The intervals from administration of the drug to active phase of labor (11.1 hours [7–24] versus 15.8 hours [7.5–29.62], P = .01), to delivery (14.0 hours [8.42–27.61] versus 20.2 hours [16.7–32.8], P = .01), and to rupture of membranes (10.0 hours [4.95–24.7] versus 15.6 hours [8.2–29.2], P = .003) were significantly shorter in the misoprostol group. All those variables were not distributed normally, so results are presented as median and interquartile range. The rates of women who needed oxytocin (68% versus 52%, P = .03) and cesarean for failed induction (9% versus 1%, P = .01) were higher in the dinoprostone group. Conclusion A single dose of 200 μg oral misoprostol was more effective for cervical ripening and labor induction than 0.5 mg of dinoprostone intracervically every 6 hours, with a maximum of four doses.

Decreased mitochondrial fatty acid oxidation in placentas from women with preeclampsia

Preeclampsia is a leading cause of maternal and fetal morbidity and mortality in high and low-income countries. The aetiology of preeclampsia is multifactorial and remains obscure. Some evidences suggest that altered placental fatty acid oxidation might play a role in the pathogenesis of preeclampsia. To reveal if placental fatty acid oxidation is reduced in preeclampsia, we evaluate the expression levels of enzymes of mitochondrial fatty acid oxidation using quantitative Real-time PCR and the fatty acid oxidation rate in placental explants. We found that long-chain 3-hydroxyacyl-CoA dehydrogenase levels and fatty acid oxidation capacity were significantly reduced in placentas from women with preeclampsia.

Second-trimester amniotic fluid proinflammatory cytokine levels in normal and overweight women.

OBJECTIVE: To estimate the relationship between different adipokines and proinflammatory mediators in amniotic fluid and maternal body mass index (BMI), calculated as weight (kg)/height (m)2. METHODS: Seventy pregnant women who underwent amniocentesis for clinical reasons at 15–20 weeks of gestation were divided into two groups according to their BMI: a control group with normal weight (BMI 20–24.9, n=35) and a case group (BMI 25 or higher, n=35). The two groups were further divided into two subgroups: overweight (BMI 25–29.9, n=22) or obese (BMI 30 or more, n=13). Comparisons of amniotic fluid cytokines (tumor necrosis factor [TNF]-&agr;, interleukin [IL]-8, IL-10, monocyte chemoattractant protein-1, resistin, and leptin) and C-reactive protein (CRP) levels were performed. The relationships between variables and maternal BMI were also analyzed. RESULTS: There were significant differences in amniotic fluid CRP and TNF-&agr; levels among the studied groups: CRP, 0.018 (±0.010), 0.019 (±0.013), and 0.035 (±0.028) mg/dL (P=.007); and TNF-&agr;, 3.98 (±1.63), 3.53 (±1.38), and 5.46 (±1.69) pg/mL (P=.003), for lean, overweight, and obese women, respectively. Both proinflammatory mediators increased in women with obesity compared with both overweight and normal women (P=.01 and P=.008 for CRP; P=.003 and P=.01 for TNF-&agr;, respectively). There were significant correlations between maternal BMI and amniotic fluid CRP (r=0.396; P=.001), TNF-&agr; (r=0.357; P=.003) and resistin (r=0.353; P=.003). CONCLUSION: Amniotic fluid CRP and TNF-&agr; levels are increased in obese women, and both are related to maternal BMI, which suggests in utero exposure to higher proinflammatory cytokines and mediators in fetuses of these women. LEVEL OF EVIDENCE: II