Prenatal diagnosis of Beckwith-Wiedemann syndrome by two- and three-dimensional ultrasonography

Beckwith-Wiedemann syndrome is a genetic syndrome characterized by macroglossia, omphalocele, fetal gigantism and neonatal hypoglycemia. The authors report a case of Beckwith-Wiedemann syndrome diagnosed in a 32-year-old primigravida in whom two-dimensional ultrasonography revealed the presence of abdominal wall cyst, macroglossia and polycystic kidneys. Three-dimensional ultrasonography in rendering mode was of great importance to confirm the previous two-dimensional ultrasonography findings.

Thalidomide protects mice against LPS-induced shock

Thalidomide has been shown to selectively inhibit TNF-a production in vitro by lipopolysaccharide (LPS)-stimulated monocytes. TNF-a has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-a and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-a, IL-6, IL-10, IL-1ß, GM-CSF and IFN-g were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-a levels were reduced by 93%, in a dose-dependent manner, and TNF-a mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ß or IFN-g. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 µg to 300 µg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death

Prenatal and postnatal depression among low income Brazilian women

Postnatal depression is a significant problem affecting 10-15% of mothers in many countries and has been the subject of an increasing number of publications. Prenatal depression has been studied less. The aims of the present investigation were: 1) to obtain information on the prevalence of prenatal and postnatal depression in low income Brazilian women by using an instrument already employed in several countries, i.e., the Edinburgh Postnatal Depression Scale (EPDS); 2) to evaluate the risk factors involved in prenatal and postnatal depression in Brazil. The study groups included 33 pregnant women interviewed at home during the second and third trimesters of pregnancy, and once a month during the first six months after delivery. Questions on life events and the mother's relationship with the baby were posed during each visit. Depressed pregnant women received less support from their partners than non-depressed pregnant women (36.4 vs 72.2%, P<0.05; Fisher exact test). Black women predominated among pre- and postnatally depressed subjects. Postnatal depression was associated with lower parity (0.4 ± 0.5 vs 1.1 ± 1.0, P<0.05; Student t-test). Thus, the period of pregnancy may be susceptible to socio-environmental factors that induce depression, such as the lack of affective support from the partner. The prevalence rate of 12% observed for depression in the third month postpartum is comparable to that of studies from other countries.

Effects of prenatal exposure to a mild chronic variable stress on body weight, preweaning mortality and rat behavior

Early stimulation has been shown to produce long-lasting effects in many species. Prenatal exposure to some strong stressors may affect development of the nervous system leading to behavioral impairment in adult life. The purpose of the present work was to study the postnatal harmful effects of exposure to variable mild stresses in rats during pregnancy. Female Holtzman rats were submitted daily to one session of a chronic variable stress (CVS) during pregnancy (prenatal stress; PS group). Control pregnant rats (C group) were undisturbed. The pups of PS and C dams were weighed and separated into two groups 48 h after delivery. One group was maintained with their own dams (PS group, N = 70; C group, N = 36) while the other PS pups were cross-fostered with C dams (PSF group, N = 47) and the other C pups were cross-fostered with PS dams (CF group, N = 58). Pups were undisturbed until weaning (postnatal day 28). The male offspring underwent motor activity tests (day 28), enriched environment tests (day 37) and social interaction tests (day 42) in an animal activity monitor. Body weight was recorded on days 2, 28 and 60. The PS pups showed lower birth weight than C pups (Duncan's test, P<0.05). The PS pups suckling with their stressed mothers displayed greater preweaning mortality (C: 23%, PS: 60%; c2 test, P<0.05) and lower body weight than controls at days 28 and 60 (Duncan's test, P<0.05 and P<0.01, respectively). The PS, PSF and CF groups showed lower motor activity scores than controls when tested at day 28 (Duncan's test, P<0.01 for PS group and P<0.05 for CF and PSF groups). In the enriched environment test performed on day 37, between-group differences in total motor activity were not detected; however, the PS, CF and PSF groups displayed less exploration time than controls (Duncan's test, P<0.05). Only the PS group showed impaired motor activity and impaired social behavior at day 42 (Duncan's test, P<0.05). In fact, CVS treatment during gestation plus suckling with a previously stressed mother caused long-lasting physical and behavioral changes in rats. Cross-fostering PS-exposed pups to a dam which was not submitted to stress counteracted most of the harmful effects of the treatment. It is probable that prenatal stress plus suckling from a previously stressed mother can induce long-lasting changes in the neurotransmitter systems involved in emotional regulation. Further experiments using neurochemical and pharmacological approaches would be interesting in this model.

Antigenic stimulation is more efficient than LPS in inducing nitric oxide production by human mononuclear cells on the in vitro granuloma reaction in schistosomiasis

Nitric oxide (NO) is an extremely important and versatile messenger in biological systems. It has been identified as a cytotoxic factor in the immune system, presenting anti- or pro-inflammatory properties under different circumstances. In murine monocytes and macrophages, stimuli by cytokines or lipopolysaccharide (LPS) are necessary for inducing the immunologic isoform of the enzyme responsible for the high-output production of NO, nitric oxide synthase (iNOS). With respect to human cells, however, LPS seems not to stimulate NO production in the same way. Addressing this issue, we demonstrate here that peripheral blood mononuclear cells (PBMC) obtained from schistosomiasis-infected patients and cultivated with parasite antigens in the in vitro granuloma (IVG) reaction produced more nitrite in the absence of LPS. Thus, LPS-induced nitrite levels are easily detectable, although lower than those detected only with antigenic stimulation. Concomitant addition of LPS and L-N-arginine methyl ester (L-NAME) restored the ability to produce detectable levels of nitrite, which had been lost with L-NAME treatment. In addition, LPS caused a mild decrease of the IVG reaction and its association with L-NAME was responsible for reversal of the L-NAME-exacerbating effect on the IVG reaction. These results show that LPS alone is not as good an NO inducer in human cells as it is in rodent cells or cell lines. Moreover, they provide evidence for interactions between LPS and NO inhibitors that require further investigation.

Congenital ventricular septal defects and prenatal exposure to cyclooxygenase inhibitors

Ventricular septal defects (VSDs) are common congenital abnormalities which have been reported to be associated with maternal fever and various environmental factors. The aim of the present study was to evaluate the effect of prenatal exposure to cyclooxygenase (COX) inhibitors on heart defects. A retrospective statistical analysis was performed using data collected in our laboratory during various teratological studies carried out on albino CRL:(WI)WUBR Wistar strain rats from 1997 to 2004. The observations were compared with concurrent and historic control data, as well as findings from other developmental toxicological studies with selective and nonselective COX-2 inhibitors. Despite the lack of significant differences in the frequency of VSDs between drug-exposed and control groups, statistical analysis by the two-sided Mantel-Haenszel test and historical control data showed a higher incidence of heart defects in offspring exposed to nonselective COX inhibitors (30.06/10,000). Unlike other specific inhibitors, aspirin (46.26/10,000) and ibuprofen (106.95/10,000) significantly increased the incidence of the VSD when compared with various control groups (5.38-19.72/10,000). No significant differences in length or weight were detected between fetuses exposed to COX inhibitors and born with VSD and non-malformed offsprings. However, a statistically significant increase of fetal body length and decrease of body mass index were found in fetuses exposed to COX inhibitors when compared with untreated control. We conclude that prenatal exposure to COX inhibitors, especially aspirin and ibuprofen, increased the incidence of VSDs in rat offspring but was not related to fetal growth retardation.

Inadequate utilization of prenatal care in two Brazilian birth cohorts

Data for two birth cohorts from two Brazilian municipalities, Ribeirão Preto in 1994 and São Luís in 1997/1998, were used to identify and compare factors associated with inadequate utilization of prenatal care and to identify factors capable of explaining the differences observed between the two cities. Prenatal care was defined as adequate or inadequate according to the recommendations of the Brazilian Ministry of Health. The chi-square test and Poisson regression were used to compare differences in the inadequacy of prenatal care utilization. The percentage of inadequacy was higher in São Luís (34.6%) than in Ribeirão Preto (16.9%). Practically the same variables were associated with inadequacy in both cities. Puerperae with lower educational level, without a companion or cohabiting, who delivered in public health units, younger than 20 years, multiparae and smokers, with low family income presented higher percentages of inadequate prenatal care utilization. However, the effects of some variables differed between the two cities. The risk for inadequate use of prenatal care was higher for women attended in the public health sector in São Luís and for cohabiting women in Ribeirão Preto. The effect of the remaining factors studied did not differ between cities. The category of admission accounted for 57.0% of the difference in the inadequate use of prenatal care between cities and marital status accounted for 45.3% of the difference. Even after adjustment for all variables, part of the difference in the inadequacy of prenatal care utilization remained unexplained.

Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species

Tolerance to lipopolysaccharide (LPS) occurs when animals or cells exposed to LPS become hyporesponsive to a subsequent challenge with LPS. This mechanism is believed to be involved in the down-regulation of cellular responses observed in septic patients. The aim of this investigation was to evaluate LPS-induced monocyte tolerance of healthy volunteers using whole blood. The detection of intracellular IL-6, bacterial phagocytosis and reactive oxygen species (ROS) was determined by flow cytometry, using anti-IL-6-PE, heat-killed Staphylococcus aureus stained with propidium iodide and 2',7'-dichlorofluorescein diacetate, respectively. Monocytes were gated in whole blood by combining FSC and SSC parameters and CD14-positive staining. The exposure to increasing LPS concentrations resulted in lower intracellular concentration of IL-6 in monocytes after challenge. A similar effect was observed with challenge with MALP-2 (a Toll-like receptor (TLR)2/6 agonist) and killed Pseudomonas aeruginosa and S. aureus, but not with flagellin (a TLR5 agonist). LPS conditioning with 15 ng/mL resulted in a 40% reduction of IL-6 in monocytes. In contrast, phagocytosis of P. aeruginosa and S. aureus and induced ROS generation were preserved or increased in tolerant cells. The phenomenon of tolerance involves a complex regulation in which the production of IL-6 was diminished, whereas the bacterial phagocytosis and production of ROS was preserved. Decreased production of proinflammatory cytokines and preserved or increased production of ROS may be an adaptation to control the deleterious effects of inflammation while preserving antimicrobial activity.

Protective effect of maternal prenatal melatonin administration on rat pups born to mothers submitted to constant light during gestation

We studied the effects of adverse conditions such as constant light (LL) on the circadian rhythm of malate (MDH, EC 1.1.1.37) and lactate (LDH, EC 1.1.1.27) dehydrogenase activities of the testes of male Wistar rats on postnatal day 28 (PN28), anxiety-like behavior (elevated plus-maze test) at PN60 and sexual behavior at PN120. The rats were assigned to mother groups on day 10 of pregnancy: control (12-h light/dark), LL (light from day 10 to 21 of pregnancy), and LL+Mel (LL and sc injection to the mothers of a daily dose of melatonin, 1 mg/kg body weight at circadian time 12, from day 17 to 21 of pregnancy). LL offspring did not show circadian rhythms of MDH (N = 62) and LDH (N = 63) activities (cosinor and ANOVA-LSD Fisher). They presented a 44.7% decrease in open-arm entries and a 67.9% decrease in time (plus-maze test, N = 15, P < 0.001, Mann-Whitney U-test and Kruskal-Wallis test), an increase in mounting (94.4%), intromission (94.5%) and ejaculation (56.6%) latencies (N = 12, P < 0.01, Mann-Whitney U-test and Kruskal-Wallis test) and lower numbers of these events (61, 59 and 73%, respectively; P < 0.01, N = 12) compared to controls. The offspring of the LL+Mel group presented MDH and LDH circadian rhythms (P < 0.05, N = 50, cosinor and ANOVA-LSD Fisher), anxiety-like and sexual behaviors similar to control. These findings supported the importance of the melatonin signal and provide evidence for the protective effects of hormones on maternal programming during gestation. This protective action of melatonin is probably related to its entrainment capacity, favoring internal coupling of the fetal multioscillatory system.

Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

Prenatal immune challenge (PIC) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10 years (May 2001 to October 2011) concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive) for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

Prenatal management, pregnancy and pediatric outcomes in fetuses with septated cystic hygroma

It has been reported that, compared with simple increased nuchal translucency, fetal cases with septated cystic hygroma (CH) are more likely to face perinatal handicaps. However, pediatric outcomes and proper prenatal counseling for this anomaly have not yet been truly defined. We performed this study to determine pregnancy and pediatric outcomes of fetuses with septated CH. We searched records for cases with septated CH and collected data for structural abnormalities, karyotype analysis, and pregnancy outcomes. Fetuses born with septated CH were also evaluated for their pediatric outcomes. Sixty-nine fetuses with septated CH were enrolled in the study. Results showed that chromosomal abnormalities were present in 28 fetuses (40.6%), and the most common aneuploidy was Turner syndrome (n=14, 20.3%); 16 (23.2%) of the remaining cases, in which aneuploidy was not found, had coexistent structural malformations; 25 (36.2%) cases had normal karyotype and morphology. The total number of live births and infants with unfavorable neurologic follow-up were 13 (18.8%) and 2 (2.9%), respectively. Septated CH is associated with poor perinatal outcomes; therefore, karyotype analysis and ultrasonographic anomaly screening should be performed as initial steps, and expectant management should be offered to couples with euploid fetuses that have normal morphology.

Mid-upper arm circumference in pregnant women and its relation to birth weight

OBJECTIVE: In order to determine the relationship between some maternal anthropometric indicators and birth weight, crown-heel length and newborn's head circumference, 92 pregnant women were followed through at the prenatal service of hospital in S. Paulo, Brazil. MATERIAL AND METHOD: The following variables were established for the mother: weight, height, mid-upper arm circumference, pre-pregnancy weight, gestational weight gain and Quetelet's index. For the newborn the following variables were recorded: birth weight, crown-heel length, head circumference and gestational age by Dubowitz's method. RESULTS: Significant associations were noted between gestational age and newborn variables. In addition, maternal mid-arm circumference (MUAC) and pre-pregnancy weight were found to be positively correlated to birth weight (r=0.399; r=0.378, respectively). The multivariate linear regression shows that gestational age, mother's arm circumference and pre-pregnancy weight continue to be significant predictors of birth weight. On the other hand, only gestational age and mother's age was associated with crown-heel length. Similarly MUAC was significantly associated with crown-heel length (r= 0.306; P=0.0030). CONCLUSION: Maternal mid-upper arm circumference is a potential indicator of maternal nutritional status. It could be used in association with other anthropometric measurements, instead of pre-pregnancy weight, as an alternative indicator to assess women at risk of poor pregnancy outcome.