Reference range of uterine artery Doppler parameters between the 11th and 14th pregnancy weeks in a population sample from Northeast Brazil

PURPOSE: To establish reference values for the first trimester uterine artery resistance index (UtA-RI) and pulsatility index (UtA-PI) in healthy singleton pregnant women from Northeast Brazil. METHODS: A prospective observational cohort study including 409 consecutive singleton pregnancies undergoing routine early ultrasound screening at 11 - 14 weeks of gestation was performed. The patients responded to a questionnaire to assess maternal epidemiological characteristics. The left and right UtA-PI and UtA-RI were examined by color and pulsed Doppler by transabdominal technique and the mean UtA-PI, mean UtA-RI and the presence of bilateral protodiastolic notching were recorded. Quartile regression was used to estimate reference values. RESULTS: The mean±standard deviation UtA-RI and UtA-PI were 0.7±0.1 and 1.5±0.5, respectively. When segregated for gestation age, mean UtA-PI was 1.6±0.5 at 11 weeks, 1.5±0.6 at 12 weeks, 1.4±0.4 at 13 weeks and 1.3±0.4 at 14 weeks' gestation and mean UtA-RI was 0.7±0.1 at 11 weeks, 0.7±0.1 at 12 weeks, 0.6±0.1 at 13 weeks and 0.6±0.1 at 14 weeks' gestation. Uterine artery bilateral notch was present in 261 (63.8%) patients. We observed that the 5th and 95th percentiles of the UtA-PI and UtA-RI uterine arteries were 0.7 and 2.3 and, 0.5 and 0.8, respectively. CONCLUSION: Normal reference range of uterine artery Doppler in healthy singleton pregnancies from Northeast Brazil was established. The 95th percentile of UtA-PI and UtA-RI values may serve as a cut-off for future prediction of pregnancy complications studies (i.e., pre-eclampsia) in Northeast Brazil.

Does hyperglycemia in pregnancy change fetal kidney growth?: a longitudinal prospective study

PURPOSE: To measure fetal renal volume in normoglycemic and hyperglycemic pregnancies. METHODS: A longitudinal prospective study was conducted and included 92 hyperglycemic and 339 normoglycemic pregnant women attended at the prenatal service of a hospital from Rio de Janeiro State. Ultrasound examinations were performed to estimate gestational age at baseline and the kidney volume was estimated using the prolate ellipsoid volume equation. RESULTS: Fetal kidney volume growth between normoglycemic and hyperglycemic pregnancies are significantly different. The fetal kidney volume growth in pregnancy is positively correlated with gestational age explained by these predictor equations, by group: normal renal volume = exp (6.186+0.09×gestational week); hyperglycemic renal volume = exp (6.978+0.071×gestational week) and an excessive growth pattern for hyperglycemic pregnancies may be established according to gestational age. CONCLUSION: This is important for early detection of abnormalities in pregnancy, particularly in diabetic mothers.

Uterine Doppler velocimetry of the uterine arteries in the second and third trimesters for the prediction of gestational outcome

PURPOSE: The aim of this longitudinal study was to investigate the value of uterine artery Doppler sonography during the second and third trimesters in the prediction of adverse pregnancy outcome in low-risk women. METHODS: From July 2011 to August 2012, a total of 205 singleton pregnant women presenting at our antenatal clinic were enrolled in this prospective study and were assessed for baseline demographic and obstetric data. They underwent ultrasound evaluation at the time of second and third trimesters, both included Doppler assessment of bilateral uterine arteries to determine the values of the pulsatility index (PI) and resistance index (RI) and presence of early diastolic notch. The endpoint of this study was assessing the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Doppler ultrasonography of the uterine artery, for the prediction of adverse pregnancy outcomes including preeclampsia, stillbirth, placental abruption and preterm labor. RESULTS: The mean age of cases was 26.4±5.11. The uterine artery PI and RI values for both second (PI: 1.1±0.42 versus 1.53±0.59, p=0.002; RI: 0.55±0.09 versus 0.72±0.13, p=0.000 respectively) and third-trimester (PI: 0.77±0.31 versus 1.09±0.46, p=0.000; RI: 0.46±0.10 versus 0.60±0.14, p=0.010 respectively) evaluations were significantly higher in patients with adverse pregnancy outcome than in normal women. Combination of PI and RI >95th percentile and presence of bilateral notch in second trimester get sensitivity and specificity of 36.1 and 97% respectively, while these measures were 57.5 and 98.2% in third trimester. CONCLUSIONS: According to our study, it seems that uterine artery Doppler may be a valuable tool for the prediction of a variety of adverse outcomes in second and third trimesters.

Changes in motor behavior during pregnancy in rats: the basis for a possible animal model of restless legs syndrome

PURPOSE:Pregnant women have a 2-3 fold higher probability of developing restless legs syndrome (RLS – sleep-related movement disorders) than general population. This study aims to evaluate the behavior and locomotion of rats during pregnancy in order to verify if part of these animals exhibit some RLS-like features.METHODS:We used 14 female 80-day-old Wistar rats that weighed between 200 and 250 g. The rats were distributed into control (CTRL) and pregnant (PN) groups. After a baseline evaluation of their behavior and locomotor activity in an open-field environment, the PN group was inducted into pregnancy, and their behavior and locomotor activity were evaluated on days 3, 10 and 19 of pregnancy and in the post-lactation period in parallel with the CTRL group. The serum iron and transferrin levels in the CTRL and PN groups were analyzed in blood collected after euthanasia by decapitation.RESULTS:There were no significant differences in the total ambulation, grooming events, fecal boli or urine pools between the CTRL and PN groups. However, the PN group exhibited fewer rearing events, increased grooming time and reduced immobilization time than the CTRL group (ANOVA, p<0.05).CONCLUSION:These results suggest that pregnant rats show behavioral and locomotor alterations similar to those observed in animal models of RLS, demonstrating to be a possible animal model of this sleep disorder.

Fetal heart rate responses during maternal resistance exercise: a pilot study

PURPOSE: To determine fetal heart rate (FHR) responses to maternal resistance exercise for the upper and lower body at two different volumes, and after 25 minutes post-exercise.METHODS: Ten pregnant women (22-24 weeks gestation, 25.2±4.4 years of age, 69.8±9.5 kg, 161.6±5.2 cm tall) performed, at 22-24, 28-32 and 34-36 weeks, the following experimental sessions: Session 1 was a familiarization with the equipment and the determination of one estimated maximum repetition. For sessions 2, 3, 4 and 5,FHR was determined during the execution of resistance exercise on bilateral leg extension and pec-deck fly machines, with 1 and 3 sets of 15 repetitions; 50% of the weight load and an estimated repetition maximum. FHR was assessed with a portable digital cardiotocograph. Results were analyzed using Student's ttest, ANOVA with repeated measures and Bonferroni (α=0.05; SPSS 17.0).RESULTS: FHR showed no significant differences between the exercises at 22-24 weeks (bilateral leg extension=143.8±9.4 bpm, pec-deck fly=140.2±10.2 bpm, p=0.34), 28-30 weeks (bilateral leg extension=138.4±12.2 bpm, pec-deck fly=137.6±14.0 bpm, p=0.75) and 34-36 weeks (bilateral leg extension=135.7±5.8 bpm, pec-deck fly=139.7±13.3 bpm, p=0.38), between the volumes(bilateral leg extension at 22-24 weeks: p=0.36, at 28-30 weeks: p=0.19 and at 34-36 weeks: p=0.87; pec-deck fly at 22-24 weeks: p=0.43, at 28-30 weeks: p=0.61 and at 34-36 weeks: p=0.49) and after 25 minutes post-exercise.CONCLUSION: Results of this pilot study would suggest that maternal resistance exercise is safe for the fetus.

Role of Tamm-Horsfall protein and uromodulin in calcium oxalate crystallization

One of the defenses against nephrolithiasis is provided by macromolecules that modulate the nucleation, growth, aggregation and retention of crystals in the kidneys. The aim of the present study was to determine the behavior of two of these proteins, Tamm-Horsfall and uromodulin, in calcium oxalate crystallization in vitro. We studied a group of 10 male stone formers who had formed at least one kidney stone composed of calcium oxalate. They were classified as having idiopathic nephrolithiasis and had no well-known metabolic risk factors involved in kidney stone pathogenesis. Ten normal men were used as controls, as was a group consisting of five normal women and another consisting of five pregnant women. Crystallization was induced by a fixed supersaturation of calcium oxalate and measured with a Coulter Counter. All findings were confirmed by light and scanning electron microscopy. The number of particulate material deposited from patients with Tamm-Horsfall protein was higher than that of the controls (P<0.001). However, Tamm-Horsfall protein decreased the particle diameter of the stone formers when analyzed by the mode of the volume distribution curve (P<0.002) (5.64 ± 0.55 µm compared to 11.41 ± 0.48 µm of uromodulin; 15.94 ± 3.93 µm and 12.45 ± 0.97 µm of normal men Tamm-Horsfall protein and uromodulin, respectively; 8.17 ± 1.57 µm and 9.82 ± 0.95 µm of normal women Tamm-Horsfall protein and uromodulin, respectively; 12.17 ± 1.41 µm and 12.99 ± 0.51 µm of pregnant Tamm-Horsfall protein and uromodulin, respectively). Uromodulin produced fewer particles than Tamm-Horsfall protein in all groups. Nonetheless, the total volume of the crystals produced by uromodulin was higher than that produced by Tamm-Horsfall protein. Our results indicate a different effect of Tamm-Horsfall protein and uromodulin. This dual behavior suggests different functions. Tamm-Horsfall protein may act on nucleation and inhibit crystal aggregation, while uromodulin may promote aggregation of calcium oxalate crystals.

Enhanced expression of Ang-(1-7) during pregnancy

Pregnancy is a physiological condition characterized by a progressive increase of the different components of the renin-angiotensin system (RAS). The physiological consequences of the stimulated RAS in normal pregnancy are incompletely understood, and even less understood is the question of how this system may be altered and contribute to the hypertensive disorders of pregnancy. Findings from our group have provided novel insights into how the RAS may contribute to the physiological condition of pregnancy by showing that pregnancy increases the expression of both the vasodilator heptapeptide of the RAS, angiotensin-(1-7) [Ang-(1-7)], and of a newly cloned angiotensin converting enzyme (ACE) homolog, ACE2, that shows high catalytic efficiency for Ang II metabolism to Ang-(1-7). The discovery of ACE2 adds a new dimension to the complexity of the RAS by providing a new arm that may counter-regulate the activity of the vasoconstrictor component, while amplifying the vasodilator component. The studies reviewed in this article demonstrate that Ang-(1-7) increases in plasma and urine of normal pregnant women. In preeclamptic subjects we showed that plasma Ang-(1-7) was suppressed as compared to the levels found in normal pregnancy. In addition, kidney and urinary levels of Ang-(1-7) were increased in pregnant rats coinciding with the enhanced detection and expression of ACE2. These findings support the concept that in normal pregnancy enhanced ACE2 may counteract the elevation in tissue and circulating Ang II by increasing the rate of conversion to Ang-(1-7). These findings provide a basis for the physiological role of Ang-(1-7) and ACE2 during pregnancy.

Routine post-weaning handling of rats prevents isolation rearing-induced deficit in prepulse inhibition

Rats reared under isolation conditions from weaning present a number of behavioral changes compared to animals reared under social conditions (group housing). These changes include deficits in prepulse inhibition (PPI) of the startle reflex to a loud sound. PPI refers to the reduction of the magnitude of the startle reflex when a relatively weak stimulus (the prepulse) precedes by an appropriate time interval the intense startle-elicing stimulus (the pulse). PPI is useful for studying sensorimotor integration. The present study evaluated the effect of handling on the impairment of PPI induced by isolation-rearing. Male Wistar rats (N = 11-15/group) were housed in groups (5 per cage and handled three times a week) or isolated (housed individually) since weaning (21 days) for 10 weeks when they reach approximately 150 g. The isolated rats were divided into "minimally handled" animals (handled once a week for cleaning purposes only) or "handled" animals (handled three times a week). This handling consisted of grasping the rat by the tail and moving it to a clean cage (approximately 5 s). A statistically significant reduction (52%) in the PPI test was found only in the isolated group with minimal handling while no difference was seen between grouped animals and isolated handled animals. These results indicate that isolation rearing causes disruption in the PPI at adult age, which serves as an index of attention deficit. This change in the sensory processing of information induced by post-weaning isolation can be prevented by handling during the development of the animal.

Elevated amniotic fluid amino acid levels in fetuses with gastroschisis

Our objective was to measure maternal plasma and amniotic fluid amino acid concentrations in pregnant women diagnosed as having fetuses with gastroschisis in the second trimester of pregnancy. Twenty-one pregnant women who had fetuses with gastroschisis detected by ultrasonography (gastroschisis group) in the second trimester and 32 women who had abnormal triple screenings indicating an increased risk for Down syndrome but had healthy fetuses (control group) were enrolled in the study. Amniotic fluid was obtained by amniocentesis, and maternal plasma samples were taken simultaneously. The chromosomal analysis of the study and control groups was normal. Levels of free amino acids and non-essential amino acids were measured in plasma and amniotic fluid samples using EZ:fast kits (EZ:fast GC/FID free (physiological) amino acid kit) by gas chromatography (Focus GC AI 3000 Thermo Finnigan analyzer). The mean levels of essential amino acids (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine) and non-essential amino acids (alanine, glycine, proline, and tyrosine) in amniotic fluid were found to be significantly higher in fetuses with gastroschisis than in the control group (P < 0.05). A significant positive correlation between maternal plasma and amniotic fluid concentrations of essential and nonessential amino acids was found only in the gastroschisis group (P < 0.05). The detection of significantly higher amino acid concentrations in the amniotic fluid of fetuses with a gastroschisis defect than in healthy fetuses suggests the occurrence of amino acid malabsorption or of amino acid leakage from the fetus into amniotic fluid.

Effects of a PPARG gene variant on obesity characteristics in Brazil

The contribution of genetic factors to the development of obesity has been widely recognized, but the identity of the genes involved has not yet been fully clarified. Variation in genes involved in adipocyte differentiation and energy metabolism is expected to have a role in the etiology of obesity. We assessed the potential association of a polymorphism in one candidate gene, peroxisome proliferator-activated receptor-gamma (PPARGg), involved in these pathways and obesity-related phenotypes in 335 Brazilians of European descent. All individuals included in the sample were adults. Pregnant women, as well as those individuals with secondary hyperlipidemia due to renal, liver or thyroid disease, and diabetes, were not invited to participate in the study; all other individuals were included. The gene variant PPARG Pro12Ala was studied by a PCR-based method and the association between this genetic polymorphism and obesity-related phenotypes was evaluated by analysis of covariance. Variant allele frequency was PPARG Ala12 = 0.09 which is in the same range as described for European and European-derived populations. No statistically significant differences were observed for mean total cholesterol, LDL cholesterol, HDL cholesterol, or triglyceride levels among PPARG genotypes in either gender. In the male sample, an association between the PPARG Pro12Ala variant and body mass index was detected, with male carriers of the Ala variant presenting a higher mean body mass index than wild-type homozygotes (28.3 vs 26.2 kg/m², P = 0.037). No effect of this polymorphism was detected in women. This finding suggests that the PPARG gene has a gender-specific effect and contributes to the susceptibility to obesity in this population.

Antiretroviral agents and acid-base balance at delivery of the neonate

Limited evidence is available regarding antiretroviral (ARV) safety for uninfected infants exposed to these drugs in utero. Our objective was to determine if ARV administered to pregnant women is associated with decreasing umbilical arterial pH and base excess in uninfected infants. A prospective study was conducted on 57 neonates divided into three groups: ZDV group, born to mothers taking zidovudine (N = 20), triple therapy (TT) group, born to mothers taking zidovudine + lamivudine + nelfinavir (N = 25), and control group (N = 12), born to uninfected mothers. Umbilical cord blood was used to determine umbilical artery gases. A test was performed to calculate the sample by comparing means by the unpaired one-tailed t-test, with a = 0.05 and ß = 20%, indicating the need for a sample of 18 newborn infants for the study groups to detect differences higher than 20%. The control and ARV groups were similar in gestational age, birth weight, and Apgar scores. Values of pH, pCO2, bicarbonate, and base excess in cord arterial blood obtained at delivery from the newborns exposed to TT were 7.23, 43.2 mmHg, 19.5 mEq/L, and -8.5 nmol/L, respectively, with no significant difference compared to the control and ZDV groups. We conclude that intrauterine exposure to ARV is not associated with a pathological decrease in umbilical arterial pH or base excess. While our data are reassuring, follow-up is still limited and needs to be continued into adulthood because of the possible potential for adverse effects of triple antiretroviral agents.

Reduced plasma levels of angiotensin-(1-7) and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

The relationship between preeclampsia and the renin-angiotensin system (RAS) is poorly understood. Angiotensin I-converting enzyme (ACE) is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II) and inactivating the vasodilator angiotensin-(1-7) (Ang-(1-7)). ACE (I/D) polymorphism is characterized by the insertion (I) or deletion (D) of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D) polymorphism was correlated with plasma Ang-(1-7) levels and several RAS components in both preeclamptic (N = 20) and normotensive pregnant women (N = 20). The percentage of the ACE DD genotype (60%) in the preeclamptic group was higher than that for the control group (35%); however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260). The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005). Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012). A reduced plasma level of Ang-(1-7) was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146). In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

Correlates of C-reactive protein levels in young adults: a population-based cohort study of 3827 subjects in Brazil

The socio-demographic, behavioral and anthropometric correlates of C-reactive protein levels were examined in a representative young adult Brazilian population. The 1982 Pelotas Birth Cohort Study (Brazil) recruited over 99% of births in the city of Pelotas that year (N = 5914). Individuals belonging to the cohort have been prospectively followed up. In 2004-2005, 77.4% of the cohort was traced, members were interviewed and 3827 individuals donated blood. Analyses of the outcome were based on a conceptual model that differentiated confounders from potential mediators. The following independent variables were studied in relation to levels of C-reactive protein in sex-stratified analyses: skin color, age, family income, education, parity, body mass index, waist circumference, smoking, fat/fiber/alcohol intake, physical activity, and minor psychiatric disorder. Geometric mean (95% confidence interval) C-reactive protein levels for the 1919 males and 1908 females were 0.89 (0.84-0.94) and 1.96 mg/L (1.85-2.09), respectively. Pregnant women and those using oral contraceptive therapies presented the highest C-reactive protein levels and all sub-groups of women had higher levels than men (P < 0.001). Significant associations between C-reactive protein levels were observed with age, socioeconomic indicators, obesity status, smoking, fat and alcohol intake, and minor psychiatric disorder. Associations were stronger at higher levels of C-reactive protein and some associations were sex-specific. We conclude that both distal (socio-demographic) and proximal (anthropometric and behavioral) factors exert strong effects on C-reactive protein levels and that the former are mediated to some degree by the latter.

The effect of epidural and general anesthesia on newborn rectal temperature at elective cesarean section

Both epidural and general anesthesia can impair thermoregulatory mechanisms during surgery. However, there is lack of information about the effects of different methods of anesthesia on newborn temperature. The purpose of this study was to determine whether there are differences in newborn rectal temperature related to type of anesthesia. Sixty-three pregnant women were randomly assigned to receive general or epidural anesthesia. Maternal core temperature was measured three times with a rectal probe just before anesthesia, at the beginning of surgery and at delivery. In addition, umbilical vein blood was sampled for pH. The rectal temperatures of the babies were recorded immediately after delivery, and Apgar scores were determined 1, 5, and 10 min after birth. The duration of anesthesia and the volume of intravenous fluid given during the procedure (833 ± 144 vs 420 ± 215 mL) were significantly higher in the epidural group than in the general anesthesia group (P < 0.0001). Maternal rectal temperatures were not different in both groups at all measurements. In contrast, newborn rectal temperatures were lower in the epidural anesthesia group than in the general anesthesia group (37.4 ± 0.3 vs 37.6 ± 0.3°C; P < 0.05) immediately after birth. Furthermore, the umbilical vein pH value (7.31 ± 0.05 vs 7.33 ± 0.01; P < 0.05) and Apgar scores at the 1st-min measurement (8.0 ± 0.9 vs 8.5 ± 0.7; P < 0.05) were lower in the epidural anesthesia group than in the general anesthesia group. Since epidural anesthesia requires more iv fluid infusion and a longer time for cesarean section, it involves a risk of a mild temperature reduction for the baby which, however, did not reach the limits of hypothermia.

Prenatally programmed hypertension: role of maternal diabetes

Epidemiological and experimental studies have led to the hypothesis of the fetal origin of adult diseases, suggesting that some adult diseases might be determined before birth by altered fetal development. Maternal diabetes subjects the fetus to an adverse environment that has been demonstrated to result in metabolic, cardiovascular and renal impairment in the offspring. The growing amount of obesity in young females in developed and some developing countries should contribute to increasing the incidence of diabetes among pregnant women. In this review, we discuss how renal and extrarenal mechanisms participate in the genesis of hypertension induced by a diabetic status during fetal development.