RANTES and developmental defects of enamel in children: A Brazilian prenatal cohort (BRISA).

OBJECTIVE: Little is known about the effect of maternal immunological factors on the etiology of developmental defects of enamel (DDE). RANTES (Regulated on Activation Normal T Cell Expressed and Secreted) is a chemokine produced by fibroblasts, lymphoid and epithelial mucosa cells in response to various external stimuli. Despite its importance for embryogenesis, RANTES expression has been demonstrated in multiple diseases characterized by inflammation, tumor and immune response, and wound healing. We hypothesized that altered levels of RANTES during pregnancy are associated with the immune and inflammatory response in women, which could lead to the occurrence of DDE in utero (DDE-iu), directly or mediated by preterm birth. Therefore, this study aimed to evaluate the direct and indirect effects of serum levels of RANTES in pregnant women in the occurrence of DDE-iu in children. METHODS: This is a longitudinal case-control study. The mothers and their children (327) were evaluated in three moments: prenatal care, post childbirth, and when the child was between 12.3 and 36 months of age. The analysis was performed with structural equation modeling, estimating the standardized coefficient (SC), adopting α = 5%. RESULTS: There was a direct and negative effect of RANTES on the outcome (SC = -0.137; p = 0.022). This association was not mediated by preterm birth (SC = 0.007; P = 0.551). When considering the specific types of DDE-iu, RANTES had a direct effect on hypoplasia (SC = -0.190; p = 0.007), but not on opacity (SC = 0.343; p = 0.074). CONCLUSION: Lower serum levels of RANTES may contribute to a higher number of teeth with DDE-iu, specifically hypoplasia. However, more evidence supported by clinical, laboratory and epidemiological studies is still needed.

Chiral Transplacental Pharmacokinetics of Fexofenadine: Impact of P-Glycoprotein Inhibitor Fluoxetine Using the Human Placental Perfusion Model.

PURPOSE: Fexofenadine is a well-identified in vivo probe substrate of P-glycoprotein (P-gp) and/or organic anion transporting polypeptide (OATP). This work aimed to investigate the transplacental pharmacokinetics of fexofenadine enantiomers with and without the selective P-gp inhibitor fluoxetine. METHODS: The chiral transplacental pharmacokinetics of fexofenadine-fluoxetine interaction was determined using the ex vivo human placenta perfusion model (n = 4). In the Control period, racemic fexofenadine (75 ng of each enantiomer/ml) was added in the maternal circuit. In the Interaction period, racemic fluoxetine (50 ng of each enantiomer/mL) and racemic fexofenadine (75 ng of each enantiomer/mL) were added to the maternal circulation. In both periods, maternal and fetal perfusate samples were taken over 90 min. RESULTS: The (S)-(-)- and (R)-(+)-fexofenadine fetal-to-maternal ratio values in Control and Interaction periods were similar (~0.18). The placental transfer rates were similar between (S)-(-)- and (R)-(+)-fexofenadine in both Control (0.0024 vs 0.0019 min-1) and Interaction (0.0019 vs 0.0021 min-1) periods. In both Control and Interaction periods, the enantiomeric fexofenadine ratios [R-(+)/S-(-)] were approximately 1. CONCLUSIONS: Our study showed a low extent, slow rate of non-enantioselective placental transfer of fexofenadine enantiomers, indicating a limited fetal fexofenadine exposure mediated by placental P-gp and/or OATP2B1. The fluoxetine interaction did not affect the non-enantioselective transplacental transfer of fexofenadine. The ex vivo placental perfusion model accurately predicts in vivo placental transfer of fexofenadine enantiomers with remarkably similar values (~0.17), and thus estimates the limited fetal exposure.

Resveratrol and grape juice: Effects on redox status and nitric oxide production of endothelial cells in in vitro preeclampsia model.

Preeclampsia (PE) is a hypertensive disorder of pregnancy and it is one of the main causes of maternal and fetal morbidity and mortality worldwide. It is known that oxidative stress plays a role in its pathophysiology, therefore we investigated the effects of trans-resveratrol, a potent antioxidant, on the Nrf2/ARE pathway, nitric oxide (NO) production, and reactive oxygen species (ROS) levels in an in vitro model of PE. Plasma from PE patients increased ARE activity in endothelial cells compared with plasma from healthy pregnant (HP), and the addition of resveratrol was able to potentiate this increase only in PE. Resveratrol also decreased ROS levels in the cells incubated with plasma from PE. Based on these results, we performed a pilot clinical study to compare the effects of serum from PE women before and 1 h after ingestion of polyphenol-rich whole red grapefruit juice incubated on endothelial cells, since grapefruit contains large amounts of resveratrol. Serum from PE patients, obtained one hour after juice intake, decreased antioxidants markers in cells compared with the serum before juice intake, besides, it increased NO production. In conclusion, resveratrol and polyphenol-rich red grape juice have potentially beneficial effects on endothelial cells incubated with PE plasma/serum, which could aid in the management of PE.

Sociodemographic factors and prenatal care behaviors associated with unplanned pregnancy in a Brazilian birth cohort study.

OBJECTIVE: To identify the sociodemographic factors and prenatal behavior characteristics associated with unplanned pregnancy. METHODS: A cross-sectional survey was conducted of mothers of newborns enrolled in a birth cohort in Ribeirão Preto, Brazil. Questionnaires were administered to postpartum women. Multiple logistic regression was used to identify sociodemographic predictors of unplanned pregnancy and to evaluate the association with adherence to prenatal care recommendations. RESULTS: The cohort included 7608 mothers: 7541 (99.1%) answered the interview and 4056 (53.8%) had an unplanned pregnancy. Adolescents were more likely to have an unplanned pregnancy (odds ratio [OR] 1.87; 95% confidence interval [CI] 1.50-2.34) as were women over 40 (OR 1.74; 95% CI 1.22-2.47). Pregnancy during adolescence (OR 1.27; 95% CI 1.09-1.48), being single (OR 7.56; 95% CI 5.98-9.56), having two or more previous births (OR 1.73; 95% CI 1.52-1.97), and being of a lower socioeconomic status were also predictors. Lack or late initiation of prenatal care, attendance at less than six prenatal visits, drinking alcohol, and smoking during pregnancy were associated with unplanned pregnancy. CONCLUSION: Unplanned pregnancies disproportionately affect women at extremes of age, single, and of low socioeconomic status. These women are less likely to adhere to prenatal care.

Can the combination of internal iliac temporary occlusion and uterine artery embolization reduce bleeding and the need for intraoperative blood transfusion in cases of invasive placentation?

OBJECTIVES: Women with invasive placentation (IP) are at high risk of life-threatening hemorrhage. In the last two decades, less invasive surgical approaches combined with endovascular procedures have proven to be safe. Most case series describe the use of temporary balloon occlusion and embolization, either combined or not. Concerning hemorrhage rates, each separate interventional approach performs better than surgery alone does, yet it is not clear whether the combination of multiple interventional techniques can be beneficial and promote a lower incidence of intrapartum bleeding. We aim to evaluate whether combining temporary balloon occlusion of the internal iliac artery and uterine artery embolization promotes better hemorrhage control than do other individual interventional approaches reported in the scientific literature in the context of cesarean birth followed by hysterectomy in patients with IP. METHODS: This is a retrospective analysis of patients with confirmed IP who underwent temporary balloon occlusion and embolization of the internal iliac arteries followed by puerperal hysterectomy. We compared patient results to data extracted from a recent systematic review and meta-analysis of the current literature that focused on interventional procedures in patients with IP. RESULTS: A total of 35 patients underwent the procedure during the study period in our institution. The mean volume of packed red blood cells and the estimated blood loss were 487.9 mL and 1193 mL, respectively. Four patients experienced complications that were attributed to the endovascular procedure. CONCLUSION: The combination of temporary balloon occlusion and uterine artery embolization does not seem to promote better hemorrhage control than each procedure performed individually does.

ABCG2 c.421C>A polymorphism alters nifedipine transport to breast milk in hypertensive breastfeeding women.

Nifedipine, a known substrate to breast cancer resistance protein (ABCG2/BCRP), is used for the treatment of hypertension during breastfeeding. This study aimed to evaluate the effect of ABCG2 c.421C>A on nifedipine transfer to breast milk (BM) in hypertensive women. Nineteen hypertensive breastfeeding women treated with 20 mg nifedipine every 12 hours were investigated. Blood and BM samples were collected simultaneously 15-30 days after delivery and at least 15 days after drug treatment. Patients genotyped as ABCG2 c.421CC showed nifedipine plasma and BM concentrations ranging from 8.32-178.1 ng/mL and 4.8-58.5 ng/mL, respectively. ABCG2 c.421C>A showed a trend towards significance (p = 0.0793) on nifedipine in BM, with concentrations approximately 3 times higher in the heterozygous 421 CA (29 ng/mL) in comparison to 421 CC (10.5 ng/mL). Nifedipine BM/plasma ratio was significantly lower in 421CC when compared to 421CA (p = 0.01). In conclusion, ABCG2 c.421C>A polymorphism is associated with higher transfer of nifedipine to BM.

Can the combination of internal iliac temporary occlusion and uterine artery embolization reduce bleeding and the need for intraoperative blood transfusion in cases of invasive placentation?

OBJECTIVES: Women with invasive placentation (IP) are at high risk of life-threatening hemorrhage. In the last two decades, less invasive surgical approaches combined with endovascular procedures have proven to be safe. Most case series describe the use of temporary balloon occlusion and embolization, either combined or not. Concerning hemorrhage rates, each separate interventional approach performs better than surgery alone does, yet it is not clear whether the combination of multiple interventional techniques can be beneficial and promote a lower incidence of intrapartum bleeding. We aim to evaluate whether combining temporary balloon occlusion of the internal iliac artery and uterine artery embolization promotes better hemorrhage control than do other individual interventional approaches reported in the scientific literature in the context of cesarean birth followed by hysterectomy in patients with IP. METHODS: This is a retrospective analysis of patients with confirmed IP who underwent temporary balloon occlusion and embolization of the internal iliac arteries followed by puerperal hysterectomy. We compared patient results to data extracted from a recent systematic review and meta-analysis of the current literature that focused on interventional procedures in patients with IP. RESULTS: A total of 35 patients underwent the procedure during the study period in our institution. The mean volume of packed red blood cells and the estimated blood loss were 487.9 mL and 1193 mL, respectively. Four patients experienced complications that were attributed to the endovascular procedure. CONCLUSION: The combination of temporary balloon occlusion and uterine artery embolization does not seem to promote better hemorrhage control than each procedure performed individually does.