Rossana Pulcineli Vieira Francisco

Resistance exercise and glycemic control in women with gestational diabetes mellitus

OBJECTIVE The objective of the study was to evaluate the effect of a resistance exercise program with an elastic band on insulin requirement and glycemic control in patients with gestational diabetes mellitus (GDM). STUDY DESIGN Sixty-four patients with gestational diabetes mellitus were randomly assigned into 2 groups: an exercise group (EG; n = 32) and a control group not submitted to the exercise program (CG; n = 32). RESULTS A significant reduction in the number of patients who required insulin was observed in the EG (7/32) compared with the CG group (18/32) (P = .005). The percentage of time spent within the proposed target glucose range (of at least 80% of weekly measurements below the limits preestablished for the disease) was significantly higher in EG compared with the CG group (EG = 0.63 ± 0.30; CG = 0.41 ± 0.31; P = .006). CONCLUSION The resistance exercise program was effective in reducing the number of patients with GDM who required insulin and in improving capillary glycemic control in this population.

Elevation of Uterine Basal Tone and Fetal Heart Rate Abnormalities After Labor Analgesia A Randomized Controlled Trial

OBJECTIVE: To estimate the effects of combined spinal–epidural and traditional epidural analgesia on uterine basal tone and its association with the occurrence of fetal heart rate (FHR) abnormalities. METHODS: Seventy-seven laboring patients who requested pain relief during labor were randomly assigned to combined spinal–epidural (n=41) or epidural analgesia (n=36). Uterine contractions and FHR were recorded 15 minutes before and after analgesia. Uterine tone was evaluated with intrauterine pressure catheter. Primary outcomes were the elevation of baseline uterine tone and occurrence of FHR prolonged decelerations or bradycardia after analgesia. The influence of other variables such as oxytocin use, hypotension, and speed of pain relief were estimated using a logistic regression model. RESULTS: The incidence of all outcomes was significantly greater in the combined spinal–epidural group compared with epidural: uterine hypertonus (17 compared with 6; P=.018), FHR abnormalities (13 compared with 2; P<.01), and both events simultaneously (11 compared with 1; P<.01). Logistic regression analysis showed the type of analgesia as the only independent predictor of uterine hypertonus (odds ratio 3.526, 95% confidence interval 1.21–10.36; P=.022). For the occurrence of FHR abnormalities, elevation of uterine tone was the independent predictor (odds ratio 18.624, 95% confidence interval 4.46–77.72; P<.001). Regression analysis also found a correlation between decrease on pain scores immediately after analgesia and the estimated probability of occurrence of hypertonus and FHR abnormalities. CONCLUSION: Combined spinal–epidural analgesia is associated with a significantly greater incidence of FHR abnormalities related to uterine hypertonus compared with epidural analgesia. The faster the pain relief after analgesia, the higher the probability of uterine hypertonus and FHR changes. CLINICAL TRIAL REGISTRATION: Umin Clinical Trials Registry, http://www.umin.ac.jp/ctr/index.htm, UMIN000001186 LEVEL OF EVIDENCE: I

Factors predicting the need for insulin therapy in patients with gestational diabetes mellitus.

AIM To determine the possible factors predicting the insulin requirement in pregnancies complicated by gestational diabetes mellitus (GDM). METHOD A total of 294 patients with GDM diagnosed by the 100-g/3-h oral glucose tolerance test (OGTT) were studied. The following factors were analyzed: maternal age, nulliparity, family history of diabetes, prepregnancy BMI, prior GDM, prior fetal macrosomia, multiple pregnancy, polyhydramnios, gestational age at diagnosis of GDM, smoking, hypertension, number of abnormal 100-g/3-h OGTT values, and glycated hemoglobin (HbA1c). The association between each factor and the need for insulin therapy was then analyzed individually. The performance of these factors to predict the probability of insulin therapy was estimated using a logistic regression model. RESULTS Univariate analysis showed a positive correlation between insulin therapy and prepregnancy BMI, family history of diabetes, hypertension, prior GDM, prior fetal macrosomia, number of abnormal 100-g/3-h OGTT values, and HbA1c (P<0.05). Prepregnancy BMI, family history of diabetes, number of abnormal 100-g/3-h OGTT values and HbA1c were statistically significant variables in the logistic regression model. CONCLUSIONS The probability of insulin therapy can be estimated in pregnant women with GDM based on prepregnancy BMI, family history of diabetes, number of abnormal 100-g/3-h OGTT values, and HbA1c concentration.

Predicting pH at birth in absent or reversed end-diastolic velocity in the umbilical arteries.

OBJECTIVE: To investigate arterial and venous blood flow in fetuses with absent or reversed end-diastolic flow in the umbilical arteries and to correlate the Doppler results with umbilical artery blood pH at birth to predict the probability of acidosis at birth. METHODS: Ninety-one fetuses from singleton pregnancies without fetal malformations with a diagnosis of absent or reversed end-diastolic flow in the umbilical arteries were prospectively studied. On the day of delivery, Doppler velocimetry of the umbilical arteries, middle cerebral artery, and ductus venosus was performed and the results were correlated with umbilical artery pH at birth at the following cutoff levels: pH < 7.20, < 7.15, < 7.10, and < 7.05. The association between fetal arterial and venous Doppler velocimetry and acidosis was then individually analyzed by the &khgr;2 and Fisher exact tests. The ability of these tests to predict the probability of acidosis at birth was estimated using a logistic regression model. RESULTS: There was a negative correlation between pH at birth and umbilical artery pulsatility index (r = –0.39; P < .001) and pulsatility index for veins in the ductus venosus (r = –0.63; P < .001). Assessment of the fetal arterial circulation (middle cerebral artery) showed no statistical correlation with pH at birth. Using logistic regression analysis, probability curves were constructed for pH values less than 7.20 (odds ratio [OR] 8.03), less than 7.15 (OR 11.92), less than 7.10 (OR 12.16), and less than 7.05 (OR 8.20). CONCLUSION: The pulsatility index for veins of the ductus venosus was related to pH at birth, demonstrating that the higher the ductus venosus pulsatility index for veins, the lower the pH at birth. Once the pulsatility index for veins in the ductus venosus is known, the probability of acidosis at birth can be estimated. LEVEL OF EVIDENCE: II-2

Fetal hemodynamic changes following maternal betamethasone administration in pregnancies with fetal growth restriction and absent end-diastolic flow in the umbilical artery

Objectives. To examine the effects of betamethasone administration on umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV) Doppler flow. Design. Longitudinal prospective study. Setting: Fetal Surveillance Unit, Department of Obstetrics and Gynecology, University of São Paulo, São Paulo, Brazil. Population. Thirty‐two singleton pregnancies complicated by fetal growth restriction with absent end‐diastolic flow in the UA. Methods. Pulsatility index (PI) of the UA, MCA and DV was measured from 26 to 34 weeks prior to and within 24 or 48 hours after starting betamethasone treatment course. Analysis of variance for repeated measures was used to determine the changes in the fetal hemodynamic Doppler flow following maternal corticosteroid administration. Main outcome measures. Improvement of UA‐PI within 24 hours and DV‐PIV (venous pulsatility) within 48 hours from the first betamethasone dose. Results. Mean gestational age at delivery was 29.3 (±1.8) weeks and birthweight was 806.6 (±228.2) g. A reduction in the UA‐PI was observed in 29 (90.6%) cases, with return of end‐diastolic flow in 22 (68.7%). The mean UA‐PI were 2.84 (±0.52) before corticosteroid administration, 2.07 (±0.56) within 24 hours and 2.42 (±0.75) after 48 hours, with a significant difference along the evaluations (p<0.001). No significant changes in the MCA Doppler were observed. DV‐PIV decreased from 1.06 (±0.23) prior corticosteroids administration to 0.73 (±0.16) within 24 hours and 0.70 (±0.19) after 48 hours (p<0.001). Conclusions. There was reduction in the umbilical artery and in the DV pulsatility indices within 24 hours from betamethasone administration that was maintained up to 48 hours.

Dysglycemias in pregnancy: from diagnosis to treatment. Brazilian consensus statement

There is an urgent need to find consensus on screening, diagnosing and treating all degrees of DYSGLYCEMIA that may occur during pregnancies in Brazil, considering that many cases of DYSGLYCEMIA in pregnant women are currently not diagnosed, leading to maternal and fetal complications. For this reason the Brazilian Diabetes Society (SBD) and the Brazilian Federation of Gynecology and Obstetrics Societies (FEBRASGO), got together to introduce this proposal. We present here a joint consensus regarding the standardization of clinical management for pregnant women with any degree of Dysglycemia, on the basis of current information, to improve medical assistance and to avoid related complications of Dysglycemia in pregnancy to the mother and the fetus. This consensus aims to standardize the diagnosis among general practitioners, endocrinologists and obstetricians allowing the dissemination of information in basic health units, public and private services, that are responsible for screening, diagnosing and treating disglycemic pregnant patients.

TLR7/TLR8 Activation Restores Defective Cytokine Secretion by Myeloid Dendritic Cells but Not by Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns.

Mother-to-child transmission (MTCT) of HIV-1 has been significantly reduced with the use of antiretroviral therapies, resulting in an increased number of HIV-exposed uninfected infants. The consequences of HIV infection on the innate immune system of both mother-newborn are not well understood. In this study, we analyzed peripheral blood and umbilical cord blood (CB) collected from HIV-1-infected and uninfected pregnant women. We measured TNF-α, IL-10 and IFN-α secretion after the stimulation of the cells with agonists of both extracellular Toll-like receptors (TLRs) (TLR2, TLR4 and TLR5) and intracellular TLRs (TLR7, TLR7/8 and TLR9). Moreover, as an indicator of the innate immune response, we evaluated the responsiveness of myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) to TLRs that are associated with the antiviral response. Our results showed that peripheral blood mononuclear cells (PBMCs) from HIV-1-infected mothers and CB were defective in TNF-α production after activation by TLR2, TLR5, TLR3 and TLR7. However, the TNF-α response was preserved after TLR7/8 (CL097) stimulation, mainly in the neonatal cells. Furthermore, only CL097 activation was able to induce IL-10 and IFN-α secretion in both maternal and CB cells in the infected group. An increase in IFN-α secretion was observed in CL097-treated CB from HIV-infected mothers compared with control mothers. The effectiveness of CL097 stimulation was confirmed by observation of similar mRNA levels of interferon regulatory factor-7 (IRF-7), IFN-α and TNF-α in PBMCs of both groups. The function of both mDCs and pDCs was markedly compromised in the HIV-infected group, and although TLR7/TLR8 activation overcame the impairment in TNF-α secretion by mDCs, such stimulation was unable to reverse the dysfunctional type I IFN response by pDCs in the HIV-infected samples. Our findings highlight the dysfunction of innate immunity in HIV-infected mother-newborn pairs. The activation of the TLR7/8 pathway could function as an adjuvant to improve maternal-neonatal innate immunity.

Vascular endothelial growth factor and β-human chorionic gonadotropin are associated with trophoblastic invasion into the tubal wall in ectopic pregnancy

OBJECTIVE To assess the association between the depth of trophoblastic penetration into the tubal wall with serum concentrations of vascular endothelial growth factor (VEGF) and β-hCG and to assess its predictive value. DESIGN Prospective study. SETTING Tertiary care university hospital. PATIENT(S) Thirty patients with ampullary pregnancy undergoing salpingectomy were analyzed. INTERVENTION(S) Trophoblastic invasion was histologically classified as stage I when limited to the tubal mucosa, stage II when extending to the muscle layer, and stage III in the case of complete tubal wall infiltration. MAIN OUTCOME MEASURE(S) The relation between depth of trophoblastic infiltration into the tubal wall with VEGF and β-hCG serum concentrations on the day of surgery. RESULT(S) An association between the depth of trophoblastic invasion and maternal serum concentrations of VEGF and β-hCG was observed. VEGF levels of 297.2 pg/mL showed 100.0% sensitivity and 90.0% specificity for stage I, and levels of 440.1 pg/mL showed 81.8% sensitivity and 88.8% specificity for stage III. Beta-hCG levels of 2590.0 mIU/mL showed 88.9% sensitivity and 80.0% specificity for stage I, and levels of 10,827.0 mUI/mL showed 72.7% sensitivity and 88.9% specificity for stage III. CONCLUSION(S) Maternal serum VEGF and β-hCG concentrations are associated with depth of trophoblastic penetration into the tubal wall.

Ductus venosus Doppler and postnatal outcomes in fetuses with absent or reversed end-diastolic flow in the umbilical arteries.

OBJECTIVE To evaluate the relationship between ductus venosus Doppler findings on the day of delivery and postnatal outcomes in pregnancies with absent or reversed end-diastolic (ARED) flow in the umbilical arteries. STUDY DESIGN Postnatal outcomes of 103 newborns of pregnancies with a diagnosis of ARED flow on Doppler velocimetry of the umbilical arteries were analyzed retrospectively between January 1997 and December 2004. Single pregnancies and fetuses without malformations were included. The cases were divided into two groups according to the flow during atrial contraction (a-wave) in the ductus venosus on the day of delivery: group A, 20 cases with absent or reversed flow in the ductus venosus and group B, 83 cases with positive flow. The results were analyzed statistically using the chi-square test, Fishers exact test and the Mann-Whitney U test with the level of significance set at 5%. RESULTS All newborns were delivered by cesarean section. Gestational age was similar in the two groups (group A: 30 weeks and group B: 30.9 weeks, P=0.23). Absent or reversed ductus venosus flow was associated with the following adverse postnatal outcomes: lower birthweight (P<0.001), lower Apgar scores in the first (P=0.001) and fifth minute (P=0.001), a higher frequency of orotracheal intubation (P=0.001) and pH at birth less than 7.20 (P<0.001), pulmonary hemorrhage (P=0.03), thrombocytopenia (P=0.02), hypoglycemia (P=0.01), intracranial hemorrhage (P=0.02), and postnatal death (P=0.007). CONCLUSION The study of ductus venosus flow may provide additional information regarding the best time for interruption of pregnancies with ARED flow in the umbilical arteries characterized by extreme prematurity.

Fetal ductus arteriosus constriction and closure: analysis of the causes and perinatal outcome related to 45 consecutive cases

Abstract Objective: The aim of this study was to analyze the causes and perinatal outcome related to fetal ductus arteriosus constriction or closure at a single center over a 26-year period. Methods: This was a retrospective analysis of 45 consecutive cases of constriction (n = 41) and closure (n = 4) from 1987 through 2013. Patients were divided into Group A (maternal use of non-steroidal anti-inflammatory drugs (NSAID), n = 29), Group B (idiopathic, n = 8), and Group C (other drugs not previously described, n = 8). Results: The median gestational age at diagnosis was 34 weeks (range, 27–38), mean systolic and diastolic velocity in the ductus arteriosus was 2.01 ± 0.66 m/s and 0.71 ± 0.46 m/s, respectively. Among the 29 cases of NSAIDs, 27.5% (8/29) have taken a single day use and 75% multiple days/doses. Right ventricular dilatation was present in 82.2% of the fetuses, tricuspid insufficiency in 86.6%, and heart failure in 22.2%. Neonatal persistent pulmonary hypertension occurred in 17.7% of the patients. Late follow-up showed all 43 survivors alive and healthy with only two deaths from unrelated causes. Conclusions: The results of this study indicate that clinically significant ductal constriction may follow maternal exposure to single doses of NSAIDs. Unknown causes or other new substances were also described, such as naphazoline, fluoxetine, isoxsuprine, caffeine and pesticides. Echocardiographic diagnosis of ductal constriction led to an active medical approach that resulted in low morbidity of this group of patients.