Obstetric Outcome in Pregnant Women on Long-term Dialysis: A Case Series

Background: Although still uncommon, pregnancy frequency in women on maintenance hemodialysis therapy has increased in the past 20 years. Most published reports suggest that intensified hemodialysis regimens result in better pregnancy outcomes. The small number of patients investigated in all reported series is the main limitation of the available studies. Study Design: Retrospective case series. Setting & Participants: Data for all pregnancies that occurred in 1988-2008 in women undergoing maintenance hemodialysis (52 pregnancies) at the Sao Paulo University Medical School (Sao Paulo, Brazil). Outcomes & Measurements: We analyzed maternal and fetal outcomes of 52 pregnancies, as well as their relationship with various clinical, laboratory, and hemodialysis parameters, such as pre-eclampsia, pregnancy before or after dialysis therapy, hemodialysis dose, polyhydramnios, anemia, and predialysis serum urea level. In addition, logistic regression models for a composite adverse fetal outcome (perinatal death or extremely premature delivery) and linear regression models for birth weight were built. Results: 87% overall rate of successful delivery, with a mean gestational age of 32.7 +/- 3.1 weeks. Pre-eclampsia was associated with a poor prognosis compared with pregnancies without pre-eclampsia: a successful delivery rate of 60% versus 92.9% (P = 0.02), extremely premature delivery rate of 77.8% versus 3.3% (P = 0.001), lower gestational age (P = 0.001), and birth weight (P = 0.001). Patients with an adverse composite fetal outcome had a higher frequency of pre-eclampsia (P = 0.001), lower frequency of polyhydramnios (P = 0.03), lower third-trimester hematocrit (P = 0.03), and higher predialysis serum urea level (P = 0.03). The same results were seen for birth weight. Limitations: Retrospective data analysis. The absence of creatinine clearance measurements did not allow evaluation of the impact of residual renal function on fetal outcome. Conclusions: Outcomes of pregnancy in women undergoing hemodialysis often are good. Preeclampsia, third-trimester hematocrit, polyhydramnios, and predialysis serum urea level are important variables associated with fetal outcome and birth weight. Am J Kidney Dis 56:77-85. (C) 2010 by the National Kidney Foundation, Inc.Inc

Association between ultrasound findings and extent of trophoblastic invasion into the tubal wall in ampullary pregnancy

Objective Predictive factors of damage to the Fallopian tube may guide the treatment of Patients with tubal pregnancy. The aim of the present study was to investigate the association between the depth of trophoblastic invasion into the tubal wall, assessed on postoperative histological examination, with the findings obtained on transvaginal sonograpby (TVS) in women with ampullary Methods Women with ampullary pregnancy undergoing salpingectomy were enrolled into the study. Only women with a finding of either an embryo with cardiac activity or a tubal ring on TVS were included in the analysis, a total of 8.5 patients. Trophoblastic invasion was assessed postoperatively and 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. The association between findings on TVS and the stage of trophoblastic invasion was evaluated. Results There was a significant association between the findings on TVS and the depth of trophoblastic invasion (P < 0.001). All patients in whom an embryo with cardiac activity bad been identified were found to have Stage II (17.9%) or Stage III (82.1%) invasion, whereas in those patients who showed a tubal ring on TVS, Stage I invasion was the most frequent finding (41.3%). Conclusions In ampullary pregnancy, the finding on TVS of an embryo with cardiac activity is associated with deeper penetration of trophoblastic tissue into the tubal wall than is the finding of a tubal ring. Copyright (C) 2009 ISUOG, Published by John Wiley & Sons, Ltd.

Early fetal cystoscopy for first-trimester severe megacystis

Objectives To report the feasibility of early fetal cystoscopy for the prenatal diagnosis and therapy of severe first-trimester megacystis. Methods Between January 2008 and February 2010, early fetal cystoscopy at 16 weeks of gestation was offered to 15 patients whose fetuses presented with severe first-trimester megacystis. All infants were followed up for 6-12 months after birth. Autopsy was always performed whenever fetal or neonatal deaths occurred. Results Seven patients decided to undergo fetal therapy, and eight elected to continue with expectant observation. One fetus died before early fetal cystoscopy was performed. Therefore, six fetuses underwent early fetal cystoscopy. Urethral atresia was diagnosed in three fetuses during fetal cystoscopy and confirmed at autopsy following termination of pregnancy at 19-20 weeks in all cases. Posterior urethral valves were diagnosed and successfully fulgurated by laser during early cystoscopy in three fetuses, two of which survived with normal renal and bladder function after birth; the remaining fetus had a postnatal diagnosis of megacystis-microcolon intestinal hypoperistalsis syndrome and died neonatally. In the expectantly managed group, no survivals were observed, even among cases with `isolated` posterior urethral valves. Conclusions Percutaneous early fetal cystoscopy is feasible for prenatal diagnosis and therapy of severe megacystis. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Visceral leishmaniasis and pregnancy: analysis of cases reported in a central-western region of Brazil

Objectives Because of the large number of cases of visceral leishmaniasis (VL) recorded in Brazil over the last few years, this disease has been showing characteristics different from previously known ones. We report cases of pregnant women treated for VL, describing their course and outcome and the chemotherapeutic medication used according to the clinical signs and symptoms of each patient. Study design We report five cases of pregnant women treated for VL in a central-western region of Brazil. Results No case of vertical transmission was observed, even in patients who were treated after delivery. One of the patients with a late diagnosis made after the onset of symptoms died. Thus, the treatment of VL during pregnancy reduces maternal mortality and the rate of vertical transmission of the disease, being safe and effective as long as the disease is diagnosed early. Conclusion At present, amphotericin B and its derivatives appear to be the best therapeutic option for the mother-child binomial.

First trimester fetal echocardiography

Objective: The aims of this study were to assess the feasibility of performing a complete fetal echocardiographic study during the first trimester of pregnancy, to establish the best week to accomplish a complete evaluation, and to find a relationship between the diameters of the cardiac valves and gestational age. Methods: 46 fetuses with normal nuchal translucency and venous duct Doppler velocimetry were submitted to echocardiographic studies by the transvaginal approach between the 11 + 0 and 14 + 6 weeks of gestation. A complete echocardiographic evaluation was defined as an examination in which the three basic planes, four-chamber, longitudinal and short-axis views, were obtained. Results: The rates of complete echocardiography evaluation were 37, 85 and 100% at 11, 12 and 13-14 weeks, respectively. The longitudinal view was the easiest to obtain and the short-axis view was the most difficult one. The diameter of the cardiac valves was compared with the crown-rump length (CRL) and there was no statistically significant difference between either the diameters of the mitral and tricuspid or the aortic and pulmonary valves. A linear growth curve was constructed to demonstrate the diameter correlations. Conclusions: The study demonstrated the feasibility of a complete fetal echocardiographic evaluation by the transvaginal approach during the first trimester of gestation. The rate of a complete evaluation increased along the period and reached 100% when the CRL was 64 mm or 13 weeks of gestational age. There was a linear correlation between the cardiac valve diameters and the CRL revealing a relationship between the cardiac and fetal development. The absence of a statistically significant difference between the left and right valve dimensions possibly means that there is no predominance of right or left chambers during this period of evaluation. Copyright (C) 2007 S. Karger AG, Basel.

NF-kappa b expression predicts clinical outcome for nasal polyposis

Objective: To correlate clinical prognosis of patients with nasal polyps to the expression of p65, c-Fos, GR alpha and GR beta. Methods: A biopsy was obtained at the first evaluation of patients with nasal polyps, and at rhinoplasty for control mucosa. Patients with nasal polyps were treated with glucocorticoids and followed for at least 60 months. The expression of p65, c-Fos, GR alpha and GR beta was determined by Real Time-PCR and correlated to clinical outcome. The end-point of resistance to glucocorticoid therapy was considered when surgery was indicated. Results: Patients with nasal polyps presented a higher expression of p65, a lower expression of GR alpha, and a lower GR alpha/GR beta ratio than control mucosa. The patients with nasal polyps who had a higher expression of p65 correlated with a poorer response to glucocorticoids, with a 3.5-fold higher risk for surgery. Conclusion: Patients with a higher p65 (NF-kappa B) expression at diagnosis were associated to a worse response to clinical treatment, suggesting one of the mechanisms of cell resistance to glucocorticoid treatment in patients with nasal polyps.

Conductive hearing loss in children with bronchopulmonary dysplasia: A longitudinal follow-up study in children aged between 6 and 24 months

Aims: To determine the occurrence of isolated and recurrent episodes of conductive hearing loss (CHL) during the first two years of life in very low birth weight (VLBW) infants with and without bronchopulmonary dysplasia (BPD). Study design, subjects and outcome measures: In a longitudinal clinical study. 187 children were evaluated at 6, 9, 12,15 18 and 24 months of age by visual reinforcement audiometry, tympanometry and auditory brain response system. Results: Of the children with BPD, 54.5% presented with episodes of CHL, as opposed to 34.7% of the children without BPD. This difference was found to be statistically significant. The recurrent or persistent episodes were more frequent among children with BPD (25.7%) than among those without BPD (8.3%). The independent variables that contributed to this finding were small for gestational age and a 5 min Apgar score. Conclusions: Recurrent CHL episodes are more frequent among VLBW infants with BPD than among VLBW infants without BPD. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Perinatal outcome of fetal atrioventricular block - One-hundred-sixteen cases from a single institution

Background-Fetal atrioventricular (AV) block is an uncommon lesion with significant mortality. Because of the rarity of this disorder, the natural course, extensive evaluation of untreated fetuses, and late follow-up remain unclear. Methods and Results-Of the 116 consecutive cases of fetal AV block studied from 1988 to 2006, only 1 was terminated, and 75% were live births. Fifty-nine cases of AV block were associated with major structural heart disease, mainly left atrial isomerism (n = 40), with only 26% of neonatal survivors. Of the 57 fetuses with normal cardiac anatomy, 41 (72%) were positive for maternal antinuclear antibodies, and 32 of these seropositive mothers did not receive any treatment. This untreated group had live-birth and 1-year infant survival rates of 93% and 90%, respectively. Five fetuses from seronegative mothers showed regression to sinus rhythm during pregnancy. The presence of major structural heart disease, hydrops, an atrial rate <= 120 bpm, and a ventricular rate <= 55 bpm were identified as risk factors for mortality. Logistic regression analysis of the whole group showed that the presence of structural heart disease was the only independent predictor of death (P < 0.001). Conclusions-This long-term study confirms that fetal AV block has a poor outcome when associated with structural heart disease and that spontaneous regression of AV block is possible in seronegative forms. The survival rate of >90% of our untreated patients with isolated forms of AV block raises concerns about any decision to intervene with immunosuppressive agents.

Single early prenatal lipopolysaccharide exposure prevents subsequent airway inflammation response in an experimental model of asthma

Aims: There has been emerging interest in the prenatal determinants of respiratory disease. In utero factors have been reported to play a role in airway development, inflammation, and remodeling. Specifically, prenatal exposure to endotoxins might regulate tolerance to allergens later in life. The present study investigated whether prenatal lipopolysaccharide (LPS) administration alters subsequent offspring allergen-induced inflammatory response in adult rats. Main methods: Pregnant Wistar rats were treated with LPS (100 mu g/kg, i.p.) on gestation day 9.5 and their ovariectomized female offspring were sensitized and challenged with OVA later in adulthood. The bronchoalveolar lavage (BAL) fluid, peripheral blood, bone marrow leukocytes and passive cutaneous anaphylaxis were evaluated in these 75-day-old pups. Key findings: OVA sensitized pups of NaCl treated rats showed an increase of leucocytes in BAL after OVA challenge. This increase was attenuated, when mothers were exposed to a single LPS injection early in pregnancy. Thus, LPS prenatal treatment resulted in (1) lower increased total and differential (macrophages, neutrophils, eosinophils and lymphocytes) BAL cellularity count; (2) increased number of total, mononuclear and polymorphonuclear cells in the peripheral blood; and (3) no differences in bone marrow cellularity or passive cutaneous anaphylaxis. Significance: In conclusion, female pups treated prenatally with LPS presented an attenuated response to experimentally-induced asthma. We observed reduced immune cell migration from peripheral blood to the lungs, with no effect on the production of bone marrow cells or antibodies. It was suggested that inflammatory events such as exposure to LPS in early fetal life can attenuate allergic inflammation in the lung, which is a common symptom in asthma. (C) 2011 Elsevier Inc. All rights reserved.

Pulmonary Maturation in Canine Foetuses From Early Pregnancy to Parturition

Development of the foetal respiratory system includes both pulmonary growth and maturation. In human medicine, a higher incidence of respiratory distress is reported in newborn males. This study aimed to identify different phases of canine foetal lung maturation throughout pregnancy, to determine the stage of pregnancy in which surfactant production begins and to compare pulmonary development of male and female foetuses. Pregnant bitches (34) were subjected to elective ovariohysterectomy and allocated into four groups, according to the stage of pregnancy: 30-40 days of pregnancy (n = 10), 41-50 days (n = 10), 51-60 days (n = 10) and bitches in the first stage of parturition (n = 4). Foetal lungs were histologically processed and evaluated by optical microscopy. The pseudoglandular phase was identified between the 35th day and 46th day of gestation; the onset of canalicular and saccular periods was observed, respectively, from the 48th day and 60th day of pregnancy. Lungs from foetuses at term were in the saccular phase; thus, the development into the alveolar period occurs in the neonatal period. The histological analyses revealed that respiratory tract development is centrifugal, from upper to lower airways. Therefore, it is possible to identify distinct development periods in different portions of the same organ. In conclusion, the saccular phase of lung development begins around 57 and 60 days of pregnancy, the period in which surfactant production is believed to occur. Male and female foetuses present similar pulmonary development from early pregnancy until parturition.

A new presynchronization system (Double-Ovsynch) increases fertility at first postpartum timed AI in lactating dairy cows

This study evaluated a novel presynchronization method, using Ovsynch prior to the Ovsynch-timed AI protocol (Double-Ovsynch) compared to Presynch-Ovsynch. Lactating Holstein (n = 337) cows, were assigned to two treatment groups: (1) Presynch (n = 180), two injections of PGF 14 d apart, followed by the Ovsynch-timed AI protocol 12 d later; (2) Double-Ovsynch (n = 157), received GnRH, PGF 7 d later, and GnRH 3 d later, followed by the Ovsynch-timed AI protocol 7 d later. All cows received the same Ovsynch-timed AI protocol: GnRH (G1) at 68 +/- 3 DIM (mean +/- SEM), PGF 7 d later, GnRH (G2) 56 h after PGF, and AI 16 to 20 h later. Pregnancy was diagnosed 39-45 d after timed AI. Double-Ovsynch increased the pregnancies per AI (P/AI) compared to Presynch-Ovsynch (49.7% vs 41.7%, P = 0.03). Surprisingly, Double-Ovsynch increased P/AI only in primiparous (65.2% vs 45.2%; P = 0.02) and not multiparous (37.5% vs 39.3%) cows. In a subset of 87 cows, ovarian ultrasonography and progesterone (P4) measurements were performed at G1 and 7 d later. Double-Ovsynch decreased the percentage of cows with low P4 (<1 ng/mL) at G1 (9.4% vs 33.3%) and increased the percentage of cows with high P4 (>= 3 ng/mL) at PGF (78.1% vs 52.3%). Thus, presynchronization of cows with Double-Ovsynch increased fertility in primiparous cows compared to a standard Presynch protocol, perhaps due to induction of ovulation in non-cycling cows and improved synchronization of cycling cows. Future studies are needed, with a larger number of cows, to further test the hypothesis of higher fertility with Double-Ovsynch, and to elucidate the physiological mechanisms that underlie apparent changes in fertility with this protocol. (C) 2008 Elsevier Inc. All rights reserved.

Vitamin D receptor haplotypes affect lead levels during pregnancy

Pregnant women are particularly susceptible to toxic effects associated with lead (Pb) exposure. Pb accumulates in bone tissue and is rapidly mobilized from bones during pregnancy, thus resulting in fetal contamination. While vitamin D receptor (VDR) polymorphisms modify bone mineralization and affect Pb biomarkers including blood (Pb-B) and serum (Pb-S) Pb concentrations, and %Pb-S/Pb-B ratio, the effects of these polymorphisms on Pb levels in pregnant women are unknown. This study aimed at examining the effects of three (Fokl, Bsml and Apal) VDR polymorphisms (and VDR haplotypes) on Pb levels in pregnant women. Pb-B and Pb-S were determined by inductively coupled plasma mass spectrometry in samples from 256 healthy pregnant women and their respective umbilical cords. Genotypes for the VDR polymorphisms were determined by PCR and restriction fragment length digestion. While the three VDR polymorphisms had no significant effects on Pb-B, Pb-S or %Pb-S/Pb-B ratio, the haplotype combining the f, a, and b alleles for the Fokl, Apal and Bsml polymorphisms, respectively, was associated with significantly lower Pb-S and %Pb-S/Pb-B (P<0.05). However, maternal VDR haplotypes had no effects on Pb levels in the umbilical cords. To our knowledge, this is the first study showing that a combination of genetic polymorphisms (haplotype) commonly found in the VDR gene affects Pb-S and %Pb-S/Pb-B ratios in pregnant women. These findings may have major implications for Pb toxicity because they may help to predict the existence of a group of subjects that is genetically less prone to Pb toxicity during pregnancy. (C) 2010 Elsevier B.V. All rights reserved.

Additive genetic relationships between scrotal circumference, heifer pregnancy, and stayability in Nellore cattle

Scrotal circumference data from 47,605 Nellore young bulls, measured at around 18 mo of age (SC18), were analyzed simultaneously with 27,924 heifer pregnancy (HP) and 80,831 stayability (STAY) records to estimate their additive genetic relationships. Additionally, the possibility that economically relevant traits measured directly in females could replace SC18 as a selection criterion was verified. Heifer pregnancy was defined as the observation that a heifer conceived and remained pregnant, which was assessed by rectal palpation at 60 d. Females were exposed to sires for the first time at about 14 mo of age (between 11 and 16 mo). Stayability was defined as whether or not a cow calved every year up to 5 yr of age, when the opportunity to breed was provided. A Bayesian linear-threshold-threshold analysis via Gibbs sampler was used to estimate the variance and covariance components of the multitrait model. Heritability estimates were 0.42 +/- 0.01, 0.53 +/- 0.03, and 0.10 +/- 0.01, for SC18, HP, and STAY, respectively. The genetic correlation estimates were 0.29 +/- 0.05, 0.19 +/- 0.05, and 0.64 +/- 0.07 between SC18 and HP, SC18 and STAY, and HP and STAY, respectively. The residual correlation estimate between HP and STAY was -0.08 +/- 0.03. The heritability values indicate the existence of considerable genetic variance for SC18 and HP traits. However, genetic correlations between SC18 and the female reproductive traits analyzed in the present study can only be considered moderate. The small residual correlation between HP and STAY suggests that environmental effects common to both traits are not major. The large heritability estimate for HP and the high genetic correlation between HP and STAY obtained in the present study confirm that EPD for HP can be used to select bulls for the production of precocious, fertile, and long-lived daughters. Moreover, SC18 could be incorporated in multitrait analysis to improve the prediction accuracy for HP genetic merit of young bulls.

Morpho-physical Recording of Bovine Conceptus (Bos indicus) and Placenta from Days 20 to 70 of Pregnancy

The study is based on 141 pregnant Bos indicus cows, from days 20 to 70 post-insemination. First, special attention was given to the macroscopically observable phenomena of attachment of the conceptus to the uterus, i.e. the implantation, from about days 20 to 30 post-insemination up to day 70, and placentome development by growth, vascularization and increase in the number of cotyledons opposite to the endometrial caruncles. Secondly, as for the conceptuses, semiquantitative, statistical analyses were performed of the lengths of chorio-allantois, amnion and yolk sac; and the different parts of the centre and two extremes of the yolk sacs were also analysed. Thirdly, the embryos/foetuses corresponding to their membranes were measured by their greatest length and by weight, and described by the appearance of external developmental phenomena during the investigated period like neurulation, somites, branchial arcs, brain vesicles, limb buds, C-form, pigmented eye and facial grooves. In conclusion, all the data collected in this study from days 20 to 70 of bovine pregnancy were compared extensively with corresponding data of the literature. This resulted in an `embryo/foetal age-scale`, which has extended the data in the literature by covering the first 8 to 70 days of pregnancy. This age-scale of early bovine intrauterine development provides model for studies, even when using slaughtered cows without distinct knowledge of insemination or fertilization time, through macroscopic techniques. This distinctly facilitates research into the cow, which is now being widely used as `an experimental animal` for testing new techniques of reproduction like in vitro fertilization, embryo transfer and cloning.

Macrophage migration inhibitory factor is up-regulated in human first-trimester placenta stimulated by soluble antigen of Toxoplasma gondii, resulting in increased monocyte adhesion on villous explants

Considering the potential role of macrophage migration inhibitory factor (MIF) in the inflammation process in placenta when infected by pathogens, we investigated the production of this cytokine in chorionic villous explants obtained from human first-trimester placentas stimulated with soluble antigen from Toxoplasma gondii (STAg). Parallel cultures were performed with villous explants stimulated with STAB, interferon-gamma (IFN-gamma), or STAB plus IFN-gamma. To assess the role of placental MIF on monocyte adhesiveness to human trophoblast, explants were co-cultured with human myelomonocytic THP-1 cells in the presence or absence of supernatant from cultures treated with STAB (SPN), SPN plus anti-MIF antibodies, or recombinant MIF. A significantly higher concentration of MIF was produced and secreted by villous explants treated with STAB or STAB plus IFN-gamma after 24-hour culture. Addition of SPN or recombinant MIF was able to increase THP-1 adhesion, which was inhibited after treatment with anti-MIF antibodies. This phenomenon was associated with intercellular adhesion molecule expression by villous explants. Considering that the processes leading to vertical dissemination of T. gondii remain widely unknown, our results demonstrate that MIF production by human first-trimester placenta is up-regulated by parasite antigen and may play an essential role as an autocrine/paracrine mediator in placental infection by T. gondii.