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.

Validation and cross-cultural adaptation of the Brazilian Portuguese version of the questionnaire for the assessment of pelvic floor disorders and their risk factors during pregnancy and postpartum.

INTRODUCTION AND HYPOTHESIS: Pelvic floor dysfunction may be treated and prevented during pregnancy and postpartum, as it decreases women's quality of life. The aim of the present study was to translate and validate the Brazilian Portuguese questionnaire for the assessment of pelvic floor disorders and their risk factors during pregnancy and postpartum. METHODS: This is a cross-sectional study. Two translators fluent in German translated the German version of the questionnaire into English. The back translation was performed by two other translators. The final version was tested on Brazilian pregnant/puerperal women. The participants answered the questionnaire twice, with an interval of 7-10 days between sessions. They also completed the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). To evaluate the test-retest reliability, we used the intraclass correlation coefficient (ICC), Cronbach's alpha coefficient, to test the internal consistency, and Pearson's linear correlation to assess construct validity. RESULTS: Sixty-six women were included (77% pregnant; 23% puerperal women), with a mean age of 26.5 ± 5.8 years and a body mass index of 26.4 ± 5.7 kg/cm2. There were no missing ceiling or floor effects. The construct validity presented a moderate correlation with the role physical domain of the SF-36 (r = -0.48), the ICC test-retest showed good reliability of 0.72, and the internal consistency was 0.71. CONCLUSIONS: These results provide evidence that the questionnaire for the assessment of pelvic floor disorders and their risk factors during pregnancy and postpartum is a valid and reliable instrument when utilized in Brazilian pregnant and postpartum women.

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.

Cross-cultural adaptation and psychometric evaluation of the Brazilian Portuguese version of the childbirth experience questionnaire.

BACKGROUND: The Childbirth Experience Questionnaire (CEQ) is a tool designed to assess women's perceptions about labor and delivery. The aim of this study was to perform the cross-cultural adaptation and validation of the Brazilian Portuguese version of the CEQ (CEQ-Br). METHODS: The original version of the CEQ was translated into Portuguese, analyzed by a committee of experts, back translated, and finally submitted to pilot-test. Two applications of the CEQ-Br were performed along with the quality of life questionnaire Medical Outcomes Study 36 - Item Short-Form Health Survey (SF-36). The SPSS software was used for statistical analysis, the intraclass correlation coefficient was used to investigate test-retest reliability, the internal consistency was investigated with the Cronbach's Alpha, and the construct validity was investigated via the Spearman correlation test. The level of significance was set at 5%. RESULTS: The study included 308 women with a mean age of 31.1 ± 8.7 years. The internal consistency results for the total CEQ-Br score was considered adequate (0.89), the test-retest showed a substantial result with an ICC of 0.90, and the construct validity was analyzed via the Spearman correlation between all SF-36 dimensions and the total CEQ-B score, the analyses were considered adequate. CONCLUSIONS: The results presented in this CEQ-Br validation study showed that the instrument was reliable in measuring the established psychometric properties and was considered valid. Therefore, the CEQ-Br can be applied to the Brazilian population.

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.

Are there differences in short-term pelvic floor muscle function after cesarean section or vaginal delivery in primiparous women? A systematic review with meta-analysis.

INTRODUCTION AND HYPOTHESIS: The literature presents controversial results regarding the role of delivery mode in pelvic floor muscle (PFM) function after birth. Some studies showed a greater impairment of PFM function after vaginal delivery compared with cesarean section, while others have not identified a significant difference between these two modes of delivery. This study aimed to investigate whether there was a difference in short-term PFM function after childbirth in primiparous women who underwent cesarean section compared with those who underwent vaginal delivery. METHODS: Up to December 2018, the PubMed-MEDLINE, CINAHL, Embase, Bireme, Scopus, Web of Science, and Science Direct databases were searched. Two independent reviewers performed the selection process based on titles, abstracts, and full-text reading. Observational studies comparing PFM function after cesarean section versus vaginal delivery in primiparous women were included. PRISMA guidelines and Cochrane recommendations were followed. Methodological quality of the primary studies was assessed through the checklist proposed by the Joanna Briggs Institute for cross-sectional studies. Random effects meta-analysis was performed to synthesize evidence regarding PFM strength in primiparous woman after vaginal delivery compared with cesarean section. The GRADE approach was applied to classify the quality of the evidence. RESULTS: Eleven studies met the inclusion criteria and were included in this review. A total of 1726 primiparous women were analyzed after childbirth. Five studies were included in the meta-analysis. No difference in PFM strength after childbirth was identified when cesarean section was compared with vaginal delivery [standardized mean difference (SMD): -0.15, 95% confidence interval (CI): -0.85 to 0.56]. Differences in PFM strength were identified when patients who underwent cesarean section were compared with those with an episiotomy or instrumented vaginal delivery (SMD: -12.51, CI 95%: -24.57 to -0.44), favoring the cesarean section group. In both cases, the quality of evidence was classified as very low because of the observational design of the included studies and population heterogeneity. CONCLUSION: There was no difference in short-term PFM strength after childbirth between primiparous women who underwent cesarean section or vaginal delivery, as assessed through vaginal manometry. However, we identified reduced PFM strength in women who underwent an episiotomy or instrumented vaginal delivery compared with those who underwent cesarean section. Nevertheless, this conclusion should be cautiously considered as the observational design of the primary studies and possible heterogeneity among the primiparous women included in the studies contributed to reducing the quality of the evidence synthesized. Future primary studies with longitudinal designs and long-term follow-up periods are needed to strengthen the quality of evidence and provide more conclusive evidence to guide clinical practice.

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.

Urinary incontinence between 12 and 24 months postpartum: a cross-sectional study nested in a Brazilian cohort from two cities with different socioeconomic characteristics.

INTRODUCTION AND HYPOTHESIS: We aimed to identify the prevalence of urinary incontinence (UI) during the postpartum period (12-24 months) in two cities with different socioeconomic indicators in Brazil (Ribeirão Preto, SP, and São Luís, MA) and to determine associated risk factors. METHODS: A cross-sectional study nested in the Brazilian Ribeirão Preto and São Luís Birth Cohort Studies (BRISA) cohort was conducted in two Brazilian municipalities (Ribeirão Preto, and São Luís). A total of 13,214 women delivered in both cities (2010-2011). We interviewed 3,751 postpartum women in Ribeirão Preto and 3275 in São Luís (2011-2013). Univariate and multivariate analyses were performed to assess factors associated with postpartum UI for each municipality. RESULTS: The prevalence of self-reported UI at 12-24 months postpartum was 16.3% (611 out of 3,751) in Ribeirão Preto and 11.4% (375 out of 3,275) in São Luís (p < 0.001). The univariate analysis performed at Ribeirão Preto showed that women who were obese, who had diabetes or gestational diabetes and who presented with excessive weight gain during gestation presented an association with postpartum UI. However, only weight gain during pregnancy remained strongly associated with UI on multivariate analysis (p = 0.009; OR 1.041 [1.010-1.073]). On the other hand, in São Luís, no risk factors were associated with postpartum UI at univariate and multivariate analysis. CONCLUSIONS: The prevalence of UI was higher in Ribeirão Preto (higher socioeconomic level) than in São Luís. Weight gain during pregnancy was statistically associated with UI in Ribeirão Preto. No independent variables remained associated in the final model with UI in São Luís.

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.

Myeloperoxidase in Hypertensive Disorders of Pregnancy and Its Relation With Nitric Oxide.

Elevated levels of myeloperoxidase have been demonstrated in women with preeclampsia where it may contribute to endothelial dysfunction mediated, in part, by nitric oxide impairment. In this study, we investigated myeloperoxidase in hypertensive disorders of pregnancy and its contribution to the impairment of the vasodilator nitric oxide. We found higher levels of myeloperoxidase in supernatant from human umbilical vein endothelial cells cultures incubated with plasma from preeclampsia group compared with healthy pregnant women. Further, we measured plasma concentration and activity of myeloperoxidase in 219 healthy pregnant women, 130 gestational hypertension (on antihypertensive therapy or not), and 143 preeclampsia patients (on antihypertensive therapy or not). We found that patients with preeclampsia and gestational hypertension without antihypertensive treatment showed higher levels and activity of this enzyme, respectively. Moreover, the inhibition of myeloperoxidase activity in vitro improved nitric oxide bioavailability. Our results indicate a higher cardiovascular risk in pregnant women with hypertensive disorders, and that active myeloperoxidase may play a role in endothelial dysfunction in these conditions by impairment of nitric oxide availability. Besides, the use of antihypertensive drugs seems to decrease enzyme levels suggesting a new protective feature for these drugs.

The telomere attrition rate is not accelerated in women born small for gestational age: A birth cohort study.

BACKGROUND: Physiologically, a reduction in telomere length (LTL) occurs with aging, but epigenetic changes may accelerate telomere shortening and also facilitate the onset of oxidative/inflammatory stress and the development of clinical/metabolic comorbidities in life spam. Although individuals born small for gestational age (SGA) may be related to those epigenetic changes, the assessment of LTL in individuals born SGA has yielded conflicting results (only cross-sectional studies) and has not been carried out in longitudinal studies. We performed a birth cohort study to evaluate the rate of telomere erosion in women born SGA in comparison to women born appropriate for gestational age (AGA) assessed at two different time points during the third decade of life. In our research, born SGA or AGA showed no difference in LTL shortening during a period of five years in the third decade of life. Our finding may have implications for understanding the natural history of diseases in lifespan because the same women (under the influence of similar environmental factors) may be accessed in different phases of life. Thus, the analysis of the present cohort population at a more advanced age may reveal a dynamics of telomere shortening different from here and its possible relation with onset of age-related diseases.

[Conjoined twins: an experience of a tertiary hospital in Southeast Brazil]. / Gêmeos conjugados: experiência de um hospital terciário do sudeste do Brasil.

PURPOSE: to analyze the occurrence of conjoined twins at a tertiary perinatology reference university hospital over a period of 25 years (January 1982 to January 2007) and to describe the successful separation of one of the pairs. METHODS: we consulted retrospectively the database of the University Hospital of the Medical School of Ribeirão Preto, University of São Paulo, Brazil, in order to determine the number of pairs of conjoined twins, their frequency, classification, gender, type of pregnancy resolution, attempted surgical separation, prenatal diagnosis and survival. RESULTS: we detected 14 pairs of conjoined twins (1/22,284 live births and 1/90 pairs of twin live births) born during this period (six males, seven females and one of indeterminate sex). The prenatal diagnosis was performed in all twins and all births were accomplished by cesarean section. The separation was possible in only one pair, which survives in excellent health conditions after eight years. Of the remaining 13, ten died on the day of birth and three survived only a few months (less than one year). CONCLUSION: Although our study revealed an abnormally high number of conjoined twins, this is a rare phenomenon, with a poor perinatal prognosis depending on the organs shared by the twins and associated malformations, especially those related to the fetal heart. Due to the poor prognosis of these pairs and to the maternal reproductive impairment caused by the need to perform body cesareans, we suggest that, based on these numbers, early interruption of these pregnancies be legally granted, as in the case of other diseases incompatible with fetal survival outside the uterus. Thus, the confirmation of a diagnosis of conjoined twins and the resolution of pregnancy should be performed at a tertiary obstetric and perinatal care center, and an authorization for the interruption of pregnancy should be obtained by judicial means.

Kinetic disposition of lorazepam with focus on the glucuronidation capacity, transplacental transfer in parturients and racemization in biological samples.

The present study investigates the kinetic disposition with focus on the racemization, glucuronidation capacity and the transplacental transfer of lorazepam in term parturients during labor. The study was conducted on 10 healthy parturients aged 18-37 years with a gestational age of 36-40.1 weeks, treated with a single oral dose of 2 mg racemic lorazepam 2-9 h before delivery. Maternal venous blood and urine samples were obtained over a 0-48 h interval and the umbilical cord sample was obtained immediately after clamping. Lorazepam enantiomers were determined in plasma and urine samples by LC-MS/MS using a Chiralcel OD-R column. In vitro racemization of lorazepam required the calculation of the pharmacokinetic parameters as isomeric mixtures. The data were fitted to two-compartment model and the pharmacokinetic parameters are reported as means (95% CI): t(1/2a) 3.2h (2.6-3.7 h), K(a) 0.23 h(-1) (0.19-0.28 h(-1)), t(1/2) 10.4h (9.4-11.3h), beta 0.068 h(-1) (0.061-0.075h(-1)), AUC(0-infinity) 175.3(ngh)/ml (145.7-204.8(ngh)/ml), Cl/F 2.6 ml/(minkg) (2.3-2.9 ml/(minkg)), Vd/F178.8l (146.5-211.1l), Fel 0.3% (0.1-0.5%), and Cl(R) 0.010 ml/(minkg) (0.005-0.015 ml/(minkg)). Placental transfer of lorazepam evaluated as the ratio of vein umbilical/maternal vein plasma concentrations, obtained as an isomeric mixture, was 0.73 (0.52-0.94). Pregnancy changes the pharmacokinetics of lorazepam, with an increase in the apparent distribution volume, an increase in apparent oral clearance, and a reduction of elimination half-life. The increase in oral clearance may indicate an increase in glucuronidation capacity, with a possible reduction in the plasma concentrations of drugs depending on glucuronidation capacity as the major metabolic pathway.

Pharmacokinetics and transplacental distribution of fentanyl in epidural anesthesia for normal pregnant women.

BACKGROUND: Fentanyl is an opioid drug widely used as a co-adjuvant in abdominal delivery, a fact that justifies its pharmacokinetic study under these conditions. OBJECTIVE: Our objective was to investigate the pharmacokinetics and placental transfer of fentanyl in parturients whose pregnancies were resolved by cesarian section with epidural anesthesia. PATIENTS AND METHODS: Ten clinically normal parturients who delivered at term received 5 ml of 2% lidocaine hydrochloride without a vasoconstrictor for skin and subcutaneous blockade, followed by epidural injection of 2 ml fentanyl citrate (0.05 mg/ml), 15 ml 0.5% bupivacaine hydrochloride with 1:200,000 epinephrine, and 10 ml 2% lidocaine hydrochloride without a vasoconstrictor. Maternal blood samples were collected at various times after injection (1--840 min), and the fentanyl plasma concentrations were determined by gas chromatography-mass spectrometry. Pharmacokinetic analysis was performed using the bi- or tri-compartmental model. The fetal/maternal ratio of the plasma fentanyl was determined at birth. RESULTS: The values of the pharmacokinetic parameters were: t(1/2)alpha=13.5 min, t(1/2)beta=192.5 min, t(1/2)gamma=620 min, AUC(0-infinity)=137.404 ng.min per milliliter, C(l)/f=464.984 ml/min, V(d)/f=299.974 l, C(l)/f/kg=6.875 ml/min per kilogram, and V(d)/f/kg=4.441 l/kg. The latency between drug administration and birth was 28.5 min, with a maternal and fetal plasma concentration of 0.310 and 0.245 ng/ml, respectively, at a median fetal/maternal ratio of 0.892. CONCLUSION: The study demonstrated a rapid passage of fentanyl from the epidural space to maternal blood and a significant transplacental transfer of maternal fentanyl of about 90%, which should serve as an alert to obstetricians.