Maternal exposure to picrotoxin modifies the response of the GABA(A) receptor during sexual behavior of adult male rat offspring

This study investigated whether perinatal exposure to picrotoxin, a GABA(A) antagonist, modifies the effect of muscimol, a GABA(A) agonist, on the sexual behavior of adult male rats. Two hours after birth and then once daily during the next 9 days of lactation, dams received picrotoxin (0.75 mg/kg subcutaneously) or saline (1 ml/kg subcutaneously). The adult male offspring from the picrotoxin and saline groups received saline (1 ml/kg intraperitoneally) or muscimol (1 mg/kg intraperitoneally), and 15 min later, their sexual behavior was assessed. Muscimol treatment in the saline-exposed group increased the mount and intromission latencies. However, these effects were absent in the picrotoxin-exposed groups. The latencies to first ejaculation, postejaculatory mount, and intromission were decreased in both picrotoxin-exposed groups relative to the saline-exposed groups. The picrotoxin + muscimol-treated rats required more intromissions to ejaculate and the picrotoxin-exposed groups made more ejaculations than the saline-exposed groups. Thus, muscimol treatment did not increase the mount and intromission latencies following picrotoxin exposure, but increased the ejaculation frequency, which did not differ between the picrotoxin + muscimol and the picrotoxin + saline groups. These data indicate that perinatal picrotoxin treatment interfered with GABA(A) receptor development Behavioural Pharmacology 23:703-709 (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Birth prevalence and characteristics of congenital toxoplasmosis in Sergipe, North-east Brazil

Objectives To estimate, by neonatal screening, the birth prevalence of congenital toxoplasmosis among live-born infants in Sergipe state, Brazil, and to investigate the clinical features of affected infants. Methods Dried blood spot specimens obtained from 15 204 neonates were assayed for the presence of anti-T. gondii IgM antibodies. Duplicate retesting was done in infants with positive and borderline results. Confirmatory testing in peripheral blood samples consisted of testing for anti-T. gondii IgG and IgM in infants and mothers. Those with possible congenital toxoplasmosis were evaluated and followed up to a median age of 20 months. Congenital infection was confirmed in the presence of persisting anti-T. gondii IgG antibodies beyond 12 months of age. All infants with confirmed infection were treated with pyrimethamine, sulfadiazine and folinic acid for 1 year. Results Fifty-three infants had detectable IgM in dried blood spot specimens. Confirmatory testing was reactive in 39/50, of which, 38 completed follow-up. Six of 15 204 newborns were diagnosed with congenital toxoplasmosis, resulting in an estimated birth prevalence of four per 10 000 [CI 95% 1.48.0]. Four infants (67%) showed signs of congenital toxoplasmosis in their first year of life; three (75%) had retinochoroidal scars, and one had cerebral calcifications. Two infants remained asymptomatic until 20 months of age. Conclusions The birth prevalence of congenital toxoplasmosis is high in the Brazilian state of Sergipe, with most of the infants showing ocular lesions. Preventive measures are strongly warranted.

Factors associated with preterm birth in Campina Grande, Paraiba State, Brazil: a case-control study

A case-control study (2008-2009) analyzed risk factors for preterm birth in the city of Campina Grande, Paraiba State, Brazil. A total of 341 preterm births and 424 controls were included. A multiple logistic regression model was used. Risk factors for preterm birth were: previous history of preterm birth (OR = 2.32; 95% CI: 1.25-4.29), maternal age (OR = 2.00; 95% CI: 1.00-4.03), inadequate prenatal care (OR = 2.15; 95% CI: 1.40-3.27), inadequate maternal weight gain (OR = 2.33; 95% CI: 1.45-3.75), maternal physical injury (OR = 2.10; 95% CI: 1.22-3.60), hypertension with eclampsia (OR = 17.08; 95% CI: 3.67-79.43) and without eclampsia (OR = 6.42; 95% CI: 3.50-11.76), hospitalization (OR = 5.64; 95% CI: 3.47-9.15), altered amniotic fluid volume (OR = 2.28; 95% CI: 1.32-3.95), vaginal bleeding (OR = 1.54; 95% CI: 1.01-2.34), and multiple gestation (OR = 22.65; 95% CI: 6.22-82.46). High and homogeneous prevalence of poverty and low maternal schooling among both cases and controls may have contributed to the fact that socioeconomic variables did not remain significantly associated with preterm birth.

Variable expressivity of osteogenesis imperfecta in a Brazilian family due to p.G1079S mutation in the COL1A1 gene

Osteogenesis imperfecta (OI) is a Mendelian disease with genetic heterogeneity characterized by bone fragility, recurrent fractures, blue sclerae, and short stature, caused mostly by mutations in COL1A1 or COL1A2 genes, which encode the pro-alpha 1(I) and pro-alpha 2(I) chains of type I collagen, respectively. A Brazilian family that showed variable expression of autosomal dominant OI was identified and characterized. Scanning for mutations was carried out using SSCP and DNA sequence analysis. The missense mutation c.3235G>A was identified within exon 45 of the COL1A1 gene in a 16-year-old girl diagnosed as having OI type I; it resulted in substitution of a glycine residue (G) by a serine (S) at codon 1079 (p.G1079S). The proband's mother had the disease signs, but without bone fractures, as did five of nine uncles and aunts of the patient. All of them carried the mutation, which was excluded in four healthy brothers of the patient's mother. This is the first description in a Brazilian family with OI showing variable expression; only one among seven carriers for the c.3235G>A mutation developed bone fractures, the most striking clinical feature of this disease. This finding has a significant implication for prenatal diagnosis in OI disease.

Implications of maternal nutrient restriction in transgenerational programming of hypertension and endothelial dysfunction across F1-F3 offspring

Aims: An extensive variety of prenatal insults are associated with an increased incidence of metabolic and cardiovascular disorders in adult life. We previously demonstrated that maternal global nutrient restriction during pregnancy leads to increased blood pressure and endothelial dysfunction in the adult offspring. This study aimed to assess whether prenatal exposure to nutritional insult has transgenerational effects in F-2 and F-3 offspring. Main methods: For this, female Wistar rats were randomly divided into two groups on day 1 of pregnancy: a control group fed standard chow ad libitum and a restricted group fed 50% of the ad libitum intake throughout gestation. At delivery, all animals were fed a standard laboratory chow diet. At 11 weeks of age, one female and one male from each restricted litter were randomly selected and mated with rats from another restricted litters in order to generate the F-2 offspring. The same procedure produced F-3 generation. Similarly, the rats in the control group were bred for each generation. Key Findings: Our findings show that the deleterious effects of maternal nutrient restriction to which the F-0 mothers were exposed may not be limited to the male first generation. In fact, we found that elevated blood pressure, an impaired vasodilatory response to acetylcholine and alterations in NO production were all transferred to the subsequent males from F-2 and F-3 generations. Significance: Our data show that global nutrient restriction during pregnancy results in a specific phenotype that can be passed transgenerationally to a second and third generation. (c) 2012 Elsevier Inc. All rights reserved.

Anaemia in pregnant women before and after the mandatory fortification of wheat and corn flours with iron

Objective: To estimate the frequency of anaemia in pregnant women before and after the fortification of flours with Fe. Design: Retrospective study developed from secondary data obtained from medical records. Setting: Two health units in Rio de Janeiro, Brazil. Subjects: Socio-economic, demographic, obstetric and Hb concentration data were collected of 778 pregnant women attending prenatal care. Two study groups were created: the first referred to the period before fortification (G1, n 391), including women whose parturition happened before June 2004; and the second referred to the period after fortification (G2, n 387), including women whose last menstrual cycle happened after June 2005. The Hb cut-off point adopted for anaemia diagnosis was <11.0 g/dl. Results: In linear regression models, when Hb concentration was expressed as a dependent variable, women in G2 presented Hb concentration 0.26 g/dl and 0.36 g/dl higher during the second and third trimesters of pregnancy, respectively, compared with G1. In logistic regression models where the dependent variable was anaemia during the second and third trimesters, it was verified that being a member of G2 was a protective factor against anaemia in the third trimester. Regarding the presence of anaemia at any gestational moment, it was verified that being a member of G2 represented a protective factor against anaemia during pregnancy. Conclusions: Results indicate the protective effect of the fortification of flours with Fe in the fight against gestational anaemia, contributing to prevention and control of this nutritional disorder among pregnant women.

Repeat pregnancies among adolescents in a tertiary hospital in Brazil

Objective: to investigate factors associated with repeat pregnancies among adolescents in a tertiary hospital in the city of Sao Paulo, Brazil. Background: Teenage mothers present a high risk of repeat pregnancies during adolescence. Most of these pregnancies are unplanned. Methods: A cross-sectional study conducted in a tertiary hospital in Sao Paulo, Brazil. The study population included 745 first-time pregnancies and 170 two or more times pregnant teenagers hospitalised for childbirth. Logistic regression models were used to identify independent factors associated with repeat pregnancy in this population. Results: Older age at first pregnancy was associated with a decreased risk of repeat pregnancies (odds ratio and 95% confidence interval 0.78 (0.68-0.89)). Prenatal examinations (0.13 (0.05-0.32)), higher education (0.83 (0.76-0.91)) and higher monthly income (0.79 (0.67-0.95)) were also protective against repeat pregnancies. Those who used contraceptives (2.76 (1.80-4.21)) and lived with their partners (2.44 (1.53-3.88)) had an increased risk of becoming pregnant more than once. Conclusion: Preventive programmes aiming to avoid repeat pregnancies in adolescents should not be restricted to the transmission of information. Behavioural changes in family planning must include access not only to adequate information but also to adequate healthcare, contraceptive methods, education and training.

Maternal smoking during pregnancy and primary headache in school-aged children: a cohort study

Background: It is not known whether smoking by mothers during pregnancy is associated with headache in their offspring. Methods: Two prospective cohorts of 869 children aged 10-11 years from Ribeirao Preto (RP) and 805 children aged 7-9 years from Sao Luis (SL) were studied. Data on maternal smoking were collected at birth. Primary headache was defined as a reporting of >= 2 episodes of headache in the past 2 weeks, without any associated organic symptoms. Results: Prevalence of headache was 28.1% in RP and 13.1% in SL as reported by the mothers and 17.5% in RP and 29.4% in SL as reported by the children. Agreement between mothers' report and children's self-report of primary headache in the child was poor. After adjustment, children whose mothers smoked >= 10 cigarettes per day during pregnancy presented higher prevalence of primary headache than their counterparts in both cohorts, as reported by the mother and in RP as reported by the children. Conclusions: Maternal smoking during pregnancy was associated with headache in 7- to 11-year-olds. With one exception, the consistency of the results, despite poor agreement between maternal and children reports of headache, indicates that maternal smoking during pregnancy may contribute to headaches in their children.

Prediction of the rate of decline in fetal hemoglobin levels between first and second transfusions in red cell alloimmune disease

Objective To determine variables that predict the rate of decline in fetal hemoglobin levels in alloimmune disease. Method Retrospective review of singleton pregnancies that underwent first and second intrauterine transfusions for treatment of fetal anemia because of maternal Rh alloimmunization in a tertiary referral center. Results Forty-one first intrauterine transfusions were performed at 26.1?weeks (standard deviation, SD, 4.6), mean volume of blood transfused was 44.4?mL (SD 23.5) and estimated feto-placental volume expansion was 51.3% (SD 14.5%). Between first and second transfusion, hemoglobin levels reduced on average 0.40?g/dl/day (SD 0.25). Stepwise multiple regression analysis demonstrated that this rate significantly correlated with hemoglobin levels after the first transfusion, the interval between both procedures, and middle cerebral artery systolic velocity before the second transfusion. Conclusion The rate of decline in fetal hemoglobin levels between first and second transfusions in alloimmune disease can be predicted by a combination of hemoglobin levels after the first transfusion, interval between both procedures, and middle cerebral artery systolic velocity before the second transfusion. (C) 2012 John Wiley & Sons, Ltd.

Estado nutricional e ganho de peso de gestantes

Caracterizou-se estado nutricional de 228 gestantes e sua influência no peso ao nascer. Trata-se de estudo retrospectivo desenvolvido num centro de saúde do município de São Paulo, com dados obtidos de prontuários. Realizou-se análise de regressão linear. Verificou-se associação entre estado nutricional inicial e final (p<0,001). A média de ganho total de peso diminuiu das gestantes que iniciaram a gravidez com baixo peso para aquelas que iniciaram com sobrepeso/obesidade (p=0,005), sendo insuficiente para 43,4 e 36,4% das gestantes com peso inicial adequado e para o total das gestantes estudadas, respectivamente. Entretanto, 37,1% daquelas que iniciaram a gravidez com sobrepeso/obesidade finalizaram com ganho excessivo, condição que, no final, afetou quase um quarto das gestantes. Anemia e baixo peso ao nascer foram pouco frequentes, porém, na análise de regressão linear, peso ao nascer associou-se com ganho de peso (p<0,05). Evidencia-se a importância do cuidado nutricional antes e durante a gravidez, para promoção da saúde materno-infantil.

Percutaneous laser ablation under ultrasound guidance for fetal hyperechogenic microcystic lung lesions with hydrops: a single center cohort and a literature review

Objective To evaluate the perinatal outcomes in hydropic fetuses with congenital microcystic pulmonary lesions that underwent percutaneous, invasive, laser therapy. Method This retrospective study reviews the literature and our experience between 2004 and 2010. Characteristics of the cystic lung lesions, liquor volume (presence of polyhydramnios or not), localization of ablation (vascular vs interstitial) and gestational age at which the procedure was performed were related to outcome (survival). Results In total, 16 fetuses with congenital lung lesions underwent invasive percutaneous laser ablation, seven performed in our center and nine published cases. Survival rate was higher in fetuses with a subsequent postnatal diagnosis of bronchopulmonary sequestration (87.5%) compared with congenital adenomatoid malformation (28.6%; p?=?0.04). The technique of vascular ablation was more successful (100%) than interstitial ablation (25.0%, p?<?0.01). Conclusion Percutaneous vascular laser ablation seems to be effective for bronchopulmonary sequestration in hydropic fetuses. Outcomes were worst following interstitial ablation for microcystic congenital adenomatoid with hydrops. (C) 2012 John Wiley & Sons, Ltd.

Expression of angiogenic factors in placenta of stressed rats

The aim of the present study was to analyse the influence of stress on pregnant rats, particularly in terms of maternal, placental and fetal weight, placental morphology and placental gene expression of the angiogenic factors Vegfa and Pgf and their receptors. The parameters were evaluated on gestation Day 20. Maternal, fetal and placental weights were statistically lower in stressed animals than controls, suggesting abnormalities in gestational physiology. Morphologically the placentas of rats subjected to stress were reduced in size and weight, with few glycogen cells and a significant increase in the number of apoptotic cells. Stress caused an increase in placental gene expression of Vegfa (P < 0.05) and a reduction in Pgf, Flt1 and Kdr expression (P < 0.05). It has been suggested that increased VEGF is associated with vasodilatation and hypotension, but in this model persistent hypertension was present. This study suggests that the limited hypotensive Vegfa response to stress-induced hypertension could result from reduced expression of Flt1/Kdr disrupting specific VEGF pathways. These findings may elucidate one of the multiple possible factors underlying how stress modulates placental physiology, and could aid the understanding of stress-induced gestational disorders.

Maternal immune activation in late gestation enhances locomotor response to acute but not chronic amphetamine treatment in male mice offspring: Role of the D1 receptor

Exposure to elevated levels of maternal cytokines can lead to functional abnormalities of the dopaminergic system in the adult offspring, including enhanced amphetamine (AMPH)-induced locomotion. Therefore, it seems reasonable to consider that offspring of challenged mothers would behave differently in models of addictive behavior, such as behavioral sensitization. Thus, we sought to evaluate the effects of prenatal exposure to lipopolysaccharide (LPS) on the locomotor response to acute and chronic AMPH treatment in male mice offspring. For this purpose, LPS (Escherichia coli 0127:B8; 120 mu g/kg) was administered intraperitoneally to pregnant Swiss mice on gestational day 17. At adulthood, male offspring were studied under one of the following conditions: (1) locomotor response to acute AMPH treatment (2.5 or 5.0 mg/kg) in an open field test; (2) behavioral sensitization paradigm, which consists of a daily injection of AMPH (1.0 mg/kg) for 10 days and observation of locomotion in the open field on days 1, 5, 10 (development phase), 15 and 17 (expression phase). The LPS stimulated offspring showed enhancement of the locomotor-stimulant effect after an acute AMPH challenge in comparison to baseline and saline pre-treated mice. They also showed development of behavioral sensitization earlier than the saline pre-treated group, although no changes between saline and LPS pre-treated groups were observed on development or expression of locomotor behavioral sensitization to AMPH. Furthermore, there was up-regulation of D1 receptor protein level within striatum in the LPS-stimulated offspring which was strongly correlated with increased grooming behavior. Taken together, our results indicate that motor and dopaminergic alterations caused by maternal immune activation are restricted to the acute AMPH challenge, mostly due to up-regulation of the D1 receptor within the mesolimbic and nigrostriatal pathways, but no locomotor differences were observed for behavioral sensitization to AMPH. (C) 2012 Elsevier B.V. All rights reserved.

Second-trimester soft markers: relation to first-trimester nuchal translucency in unaffected pregnancies

Objective Genetic sonography following first-trimester combined screening appears to increase substantially detection rates for Down syndrome but it relies on the unproved assumption of independence between these tests. In this study we aimed to investigate the relationship between first-trimester nuchal translucency (NT) and a series of second-trimester soft markers and structural defects in unaffected pregnancies. Methods NT measurement in the first trimester was followed by second-trimester scan (18 to 23 + 6 weeks) including examination for three categorical markers (intracardiac echogenic foci, hyperechogenic bowel and structural defects) and measurement of nasal bone length, nuchal-fold thickness, femur length, humerus length, renal pelvis diameter and prenasal thickness. All continuous variables were expressed in multiples of the median (MoM) for gestation and correlation coefficients between log-transformed NT and second-trimester variables were calculated. In addition, frequencies of soft markers and structural defects in cases with increased NT were compared to those with normal NT, using MoM cut-offs. Results In a dataset of 1970 cases, NT was significantly correlated (P < 0.05) with all second-trimester continuous variables, the correlation being strongest for nuchal-fold thickness (r = 0.10). There was a higher frequency of cases with second-trimester nuchal-fold thickness above the 97.5th centile (10.7 vs. 2.2%) and hyperechogenic bowel (2.4 vs. 0.1%) in cases with increased NT. Conclusions Straightforward reassessment of risk using likelihood ratios derived from the second-trimester genetic sonogram might lead to inaccurate estimates. Multivariate models using continuous second-trimester variables might be preferable in sequential screening strategies. Copyright. 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Feelings of women regarding end-of-life decision making after ultrasound diagnosis of a lethal fetal malformation

Objective: this study investigated the feelings of women regarding end-of-life decision making after ultrasound diagnosis of a lethal fetal malformation. The aim of this study was to present the decision making process of women that chose for pregnancy termination and to present selected speeches of women about their feelings. Design: open psychological interviews conducted by a psychologist immediately after the diagnosis of fetal malformation by ultrasound. Analysis of the results was performed through a content analysis technique. Setting: the study was carried out at a public university hospital in Brazil. Participants: 249 pregnant women who had received the diagnosis of a severe lethal fetal malformation. Findings: fetal anencephaly was the most frequent anomaly detected in 135 cases (54.3%). Termination of pregnancy was decided by 172 (69.1%) patients and legally authorised by the judiciary (66%). The reason for asking for termination was to reduce suffering in all of them. In the 77 women who chose not to terminate pregnancy (30.9%), the reasons were related to feelings of guilt (74%). Key conclusions: the results support the importance of psychological counselling for couples when lethal fetal malformation is diagnosed. The act of reviewing moral and cultural values and elements of the unconscious provides assurance in the decision-making process and mitigates the risk of emotional trauma and guilt that can continue long after the pregnancy is terminated. (C) 2011 Elsevier Ltd. All rights reserved.