Avaliação da concentração de vitamina A materna e de neonatos prematuros e a termo

Vitamin A is an essential nutrient for many physiological processes such as growth and development, so that their adequate nutritional state is essential during pregnancy and lactation. Lactating women and children in breastfeeding are considered risk groups for vitamin A deficiency and some factors may increase the risk of vitamin A deficiency, such as prematurity. The aim of this work was to evaluate the vitamin A concentration in preterm and term lactating women and newborns by determination of retinol in maternal serum, umbilical cord serum and breast milk collected until 72 hours postpartum. 182 mothers were recruited and divided into preterm group (GPT; n = 118) and term group (GT, n = 64). In preterm group were also analyzed transition milk (7th-15th day; n = 68) and mature milk (30th-55th day; n = 46) samples. Retinol was analyzed by high-performance liquid chromatography (HPLC). Maternal retinol concentration in serum was 48.6 ± 12.3 µg/dL in GPT and 42.8 ± 16.3 µg/dL in the GT (p <0.01). Cord serum retinol was 20.4 ± 7.4 µg/dL in GPT and 23.2 ± 7.6 µg/dL in GT (p> 0.05). Among newborns, 43% of premature and 36% of term had low levels of serum retinol in umbilical cord (<20 µg/dL). In colostrum, the retinol in preterm and term groups had an average of 100.8 ± 49.0 µg/dL and 127.5 ± 65.1 µg/dL, respectively (p <0.05). The retinol average in preterm milk increased to 112.5 ± 49.7 µg/dL in transition phase and decreased to 57.2 ± 23.4 µg/dL in mature milk, differing significantly in all stages (p <0.05). When comparing with the recommendation of vitamin A intake (400 µg/day) GT colostrum reached the recommendation for infants, but in GPT the recommendation was not achieved at any stage. Mothers of premature infants had higher serum retinol than mothers at term; however, this was not reflected in serum retinol of umbilical cord, since premature had lower concentration of retinol. Such condition can be explained due to lower maternal physiological hemodilution and placental transfer of retinol to the fetus during preterm gestation. Comparison of retinol in colostrum showed lower concentrations in GPT; however the transition phase there was a significant increase of retinol content released by the mammary gland of preterm mothers. This situation highlights a specific physiological adaptation of prematurity, likely to more contribute to formation of hepatic reserves of retinol in premature infants.

Antenatal origins of reduced lung function : but not asthma?

Peer reviewed

Dysregulation of placental cystathionine-β-synthase promotes fetal growth restriction

Fetal growth restriction (FGR) is characterized by the birth weight and body mass below the tenth percentile for gestational age. FGR is a major cause of perinatal morbidity and mortality and babies born with FGR are prone to develop cardiovascular diseases later in life. The underlying pathology of FGR is inadequate placental transfer of nutrients from mother to fetus, which can be caused by placental insufficiency. Hydrogen sulfide (H2S), a gaseous messenger is produced endogenously by cystathionine-lyase (Cth), cystathionine-β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), which are present in human placenta. Recently, we demonstrated that the dysregulation of H2S/Cth pathway is associated with preeclampsia and blockade of CSE activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in H2S pathways promote FGR and H2S donor restores fetal growth in mice where CBS or CSE activity has been compromised. Western blotting and qPCR revealed that placental CBS expressions were significantly reduced in women with FGR. ELISA analysis showed reduced placental growth factor production (PlGF) from first trimester (8–12 weeks gestation) human placental explants following inhibition of CBS activity by aminooxyacetic acid (AOA). Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction. This was associated with reduced PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor treated mice. These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia.

Dysregulation of placental cystathionine-β-synthase impact on fetal growth restriction

INTRODUCTION: Fetal growth restriction (FGR), which causes perinatal morbidity and mortality, is characterized by birth weight and body mass being below 10th percentile for gestational age. FGR babies are prone to develop cardiovascular diseases later in life. Inadequate placental transfer of nutrients from mother to fetus due to placental insufficiency is considered the underlying cause of FGR. Recently, we demonstrated that blockade of cystathionine-γ-lyase (CSE) activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in cystathionine-β-synthase (CBS) / H2S pathway may promote FGR. METHODS: Placental CBS expressions were determined in women with FGR (n=9) and normal controls (n=14) by Western blotting and real-time qPCR. ELISA was used to determine angiogenic factors levels in plasma and first-trimester (8–12 weeks gestation) human placental explants. Time pregnant mice were treated with CBS inhibitor, aminooxyacetic acid (AOA). Mean arterial blood pressure (MBP), histological assessments of placenta and embryos were performed. RESULTS: Placental CBS expressions were significantly reduced in women with FGR. Inhibition of CBS activity by AOA reduced PlGF production from first-trimester human placental explants, Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction, which was associated with reduced placental PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor-treated animals. Furthermore, H2S donor GYY4137 treatment restored fetal growth in pregnant mice exposed to high level of sFlt-1. CONCLUSIONS: These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia opening up the therapeutic potentials of H2S therapy in this condition.

Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics

Sex differences occur in most non-communicable diseases, including metabolic diseases, hypertension, cardiovascular disease, psychiatric and neurological disorders and cancer. In many cases, the susceptibility to these diseases begins early in development. The observed differences between the sexes may result from genetic and hormonal differences and from differences in responses to and interactions with environmental factors, including infection, diet, drugs and stress. The placenta plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent adult health and accounts, in part for the developmental origin of health and disease (DOHaD). There is accumulating evidence to demonstrate the sex-specific relationships between diverse environmental influences on placental functions and the risk of disease later in life. As one of the few tissues easily collectable in humans, this organ may therefore be seen as an ideal system for studying how male and female placenta sense nutritional and other stresses, such as endocrine disruptors. Sex-specific regulatory pathways controlling sexually dimorphic characteristics in the various organs and the consequences of lifelong differences in sex hormone expression largely account for such responses. However, sex-specific changes in epigenetic marks are generated early after fertilization, thus before adrenal and gonad differentiation in the absence of sex hormones and in response to environmental conditions. Given the abundance of X-linked genes involved in placentogenesis, and the early unequal gene expression by the sex chromosomes between males and females, the role of X- and Y-chromosome-linked genes, and especially those involved in the peculiar placenta-specific epigenetics processes, giving rise to the unusual placenta epigenetic landscapes deserve particular attention. However, even with recent developments in this field, we still know little about the mechanisms underlying the early sex-specific epigenetic marks resulting in sex-biased gene expression of pathways and networks. As a critical messenger between the maternal environment and the fetus, the placenta may play a key role not only in buffering environmental effects transmitted by the mother but also in expressing and modulating effects due to preconceptional exposure of both the mother and the father to stressful conditions.

The impact of maternal inflammation and maternal stress in the regulation of neurodevelopment and physiological function

The mechanisms governing fetal development follow a tightly regulated pattern of progression such that interference at any one particular stage is likely to have consequences for all other stages of development in the physiological system that has been affected thereafter. These disturbances can take the form of many different events but two of the most common and widely implicated in causing detrimental effects to the developing fetus are maternal immune activation (MIA) and maternal stress. MIA has been shown to cause an increase in circulating proinflammatory cytokines in both the maternal and fetal circulation. This increase in proinflammatory mediators in the fetus is thought to occur by fetal production rather than through exchange between the maternal-fetal interface. In the case of maternal stress it is increased levels of stress related hormones such as cortisol/corticosterone which is thought to elicit the detrimental effects on fetal development. In the case of both maternal infection and stress the timing and nature of the insult generally dictates the severity and type of effects seen in affected offspring. We investigated the effect of a proinflammatory environment on neural precursor cells of which exposure resulted in a significant decrease in the normal rate of proliferation of NPCs in culture but did not have any effect on cell survival. These effects were seen to be age dependent. Using a restraint stress model we investigated the effects of prenatal stress on the development of a number of different physiological systems in the same cohort of animals. PNS animals exhibited a number of aberrant changes in cardiovascular function with altered responses to stress and hypertension, modifications in respiratory responses to hypercapnic and hypoxic challenges and discrepancies in gastrointestinal innervation. Taken together these findings suggest that both maternal infection and maternal stress are detrimental to the normal development of the fetus.

The Effects of Brominated Flame Retardants on Thyroid Hormone Homeostasis in Human Placenta Tissues and Cell Culture

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants (BFRs) that have been heavily used in consumer products such as furniture foams, plastics, and textiles since the mid-1970’s. BFRs are added to products in order to meet state flammability standards intended to increase indoor safety in the event of a fire. The three commercial PBDE mixtures, Penta-, Octa-, and DecaBDE, have all been banned in the United States, however, limited use of DecaBDE is still permitted. PBDEs were phased out of production and added to the Stockholm Convention due to concerns over their environmental persistence and toxicity. Human exposure to PBDEs occurs primarily through the inadvertent ingestion of contaminated house dust, as well as though dietary sources. Despite the phase-out and discontinued use of PBDEs, human exposure to this class of chemicals is likely to continue for decades due to the continued use of treated products and existing environmental reservoirs of PBDEs. Extensive research over the years has shown that PBDEs disrupt thyroid hormone (TH) levels and neurodevelopmental endpoints in rodent and fish models. Additionally, there is growing epidemiological evidence linking PBDE exposure in humans to altered TH homeostasis and neurodevelopmental impairments in children. Due to the importance of THs throughout gestation, there is a great need to understand the effects of BFRs on the developing fetus. Specifically, the placenta plays a critical role in the transport, metabolism, and delivery of THs to the fetal compartment during pregnancy and is a likely target for BFR bioaccumulation and endocrine disruption. The central hypothesis of this dissertation research is that BFRs disrupt the activity of TH sulfotransferase (SULT) enzymes, thereby altering TH concentrations in the placenta.

In the first aim of this dissertation research, the concentrations of PBDEs and 2,4,6-TBP were measured in a cohort of 102 placenta tissue samples from an ongoing pregnancy cohort in Durham, NC. Methods were developed for the extraction and analysis of the BFR analytes. It was found that 2,4,6-TBP was significantly correlated with all PBDE analytes, indicating that 2,4,6-TBP may share common product applications with PBDEs or that 2,4,6-TBP is a metabolite of PBDE compounds. Additionally, this was the first study to measure 2,4,6-TBP in human placenta tissues.

In the second aim of this dissertation research, the placenta tissue concentrations of THs, as well as the endogenous activity of deiodinase (DI) and TH SULT enzymes were quantified using the same cohort of 102 placenta tissue samples. Enzyme activity was detected in all samples and this was the first study to measure TH DI and SULT activity in human placenta tissues. Enzyme activities and TH concentrations were compared with BFR concentrations measured in Aim 1. There were few statistically significant associations observed for the combined data, however, upon stratifying the data set based on infant sex, additional significant associations were observed. For example, among males, those with the highest concentrations of BDE-99 in placenta had T3 levels 0.80 times those with the lowest concentration of BDE-99 (95% confidence interval (CI): 0.59, 1.07). Whereas females with the highest concentrations of BDE-99 in placenta had T3 levels 1.50 times those with the lowest concentration of BDE-99 (95% CI: 1.10, 2.04). Additionally, all BFR analyte concentrations were higher in the placenta of males versus females and they were significantly higher for 2,4,6-TBP and BDE-209. 3,3’-T2 SULT activity was significantly higher in female placenta tissues, while type 3 DI activity was significantly higher in male placenta tissues. This research is the first to show sex-specific differences in the bioaccumulation of BFRs in human placenta tissue, as well as differences in TH concentrations and endogenous DI and SULT activity. The underlying mechanisms of these observed sex differences warrant further investigation.

In the third aim of this dissertation research, the effects of BFRs were examined in a human choriocarcinoma placenta cell line, BeWo. Michaelis-Menten parameters and inhibition curves were calculated for 2,4,6-TBP, 3-OH BDE-47, and 6-OH BDE-47. 2,4,6-TBP was shown to be the most potent inhibitor of 3,3’-T2 SULT activity with a calculated IC50 value of 11.6 nM. It was also shown that 2,4,6-TBP and 3-OH BDE-47 exhibit mixed inhibition of 3,3’-T2 sulfation in BeWo cell homogenates. Next, a series of cell culture exposure experiments were performed using 1, 6, 12, and 24 hour exposure durations. Once again, 2,4,6-TBP was shown to be the most potent inhibitor of basal 3,3’-T2 SULT activity by significantly decreasing activity at the high and medium dose (1 M and 0.5 M, respectively) at all measured time points. Interestingly, BDE-99 was also shown to inhibit basal 3,3’-T2 SULT activity in BeWo cells following the 24 hour exposure, despite exhibiting no inhibitory effects in the BeWo cell homogenate experiments. This indicates that BDE-99 must act through a pathway other than direct enzyme inhibition. Following exposures, the TH concentrations in the cell culture growth media and mRNA expression of TH-related genes were also examined. There was no observed effect of BFR treatment on these endpoints. Future work should focus on determining the downstream biological effects of TH SULT disruption in placental cells, as well as the underlying mechanisms of action responsible for reductions in basal TH SULT activity following BFR exposure.

This was one of the first studies to measure BFRs in a cohort of placenta tissue samples from the United States and the first study to measure THs, DI activity, and SULT activity in human placenta tissues. This research provides a novel contribution to our growing understanding of the effects of BFRs on TH homeostasis within the human placenta, and provides further evidence for sex-specific differences within this important organ. Future research should continue to investigate the effects of environmental contaminants on TH homeostasis within the placenta, as this represents the most critical and vulnerable stage of human development.

Maternal-Fetal Attachment and Health Behaviors among Women with HIV/AIDS

Background: Mothers with HIV often face personal and environmental risks for poor maternal health behaviors and infant neglect, even when HIV transmission to the infant was prevented. Maternal-fetal attachment (MFA), the pre-birth relationship of a woman with her fetus, may be the precursor to maternal caregiving. Using the strengths perspective in social work, which embeds MFA within a socio-ecological conceptual framework, it is hypothesized that high levels of maternal-fetal attachment may protect mothers and infants against poor maternal health behaviors. Objective: To assess whether MFA together with history of substance use, living marital status, planned pregnancy status, and timing of HIV diagnosis predict three desirable maternal health behaviors (pregnancy care, adherence to prenatal antiretroviral therapy–ART, and infant’s screening clinic care) among pregnant women with HIV/AIDS. Method: Prospective observation and hypothesis-testing multivariate analyses. Over 17 consecutive months, all eligible English- or Spanish-speaking pregnant women with HIV ( n = 110) were approached in the principal obstetric and screening clinics in Miami-Dade County, Florida at 24 weeks’ gestation; 82 agreed to enroll. During three data collection periods from enrollment until 16 weeks after childbirth (range: 16 to 32 weeks), participants reported on socio-demographic and predictor variables, MFA, and pregnancy care. Measures of adherence to ART and infant care were extracted from medical records. Findings: Sociodemographic, pregnancy, and HIV disease characteristics in this sample suggest changes in the makeup of HIV-infected pregnant women parallel to the evolution of the HIV epidemic in the USA over the past two decades. The MFA model predicted maternal health behaviors for pregnancy care (R2 = .37), with MFA, marital living status, and planned pregnancy status independently contributing ( = .50, = .28, = .23, respectively). It did not predict adherence to ART medication or infant care. Relevance: These findings provide the first focused evidence of the protective role of MFA against poor maternal health behaviors among pregnant women with HIV, in the presence of adverse life circumstances. Social desirability biases in some self-report measures may limit the findings. Suggestions are made for orienting future inquiry on maternal health behaviors during childbirth toward relationship and protection.

Immunologically silent cancer clone transmission from mother to offspring

Rare cases of possible materno-fetal transmission of cancer have been recorded over the past 100 years but evidence for a shared cancer clone has been very limited. We provide genetic evidence for mother to offspring transmission, in utero, of a leukemic cell clone. Maternal and infant cancer clones shared the same unique BCR-ABL1 genomic fusion sequence, indicating a shared, single-cell origin. Microsatellite markers in the infant cancer were all of maternal origin. Additionally, the infant, maternally- derived cancer cells had a major deletion on one copy of chromosome 6p that included deletion of HLA alleles that were not inherited by the infant (i.e., foreign to the infant), suggesting a possible mechanism for immune evasion.

Neonatal Examination

This chapter describes the development from embryo to fetus in the various stages and the factors which can impact on normal fetal development

Fetal Development

The chapter explains fetal development fro embryo to fetus and the factors which impact on fetal development

Prevalence and risk of Down syndrome in monozygotic and dizygotic multiple pregnancies in Europe: implications for prenatal screening

OBJECTIVE: To determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome.

DESIGN: Population-based prevalence study based on EUROCAT congenital anomaly registries.

SETTING: Eight European countries.

POPULATION: 14.8 million births 1990-2009; 2.89% multiple births.

METHODS: DS cases included livebirths, fetal deaths from 20 weeks, and terminations of pregnancy for fetal anomaly (TOPFA). Zygosity is inferred from like/unlike sex for birth denominators, and from concordance for DS cases.

MAIN OUTCOME MEASURES: Relative risk (RR) of DS per fetus/baby from multiple versus singleton pregnancies and per pregnancy in monozygotic/dizygotic versus singleton pregnancies. Proportion of prenatally diagnosed and pregnancy outcome.

STATISTICAL ANALYSIS: Poisson and logistic regression stratified for maternal age, country and time.

RESULTS: Overall, the adjusted (adj) RR of DS for fetus/babies from multiple versus singleton pregnancies was 0.58 (95% CI 0.53-0.62), similar for all maternal ages except for mothers over 44, for whom it was considerably lower. In 8.7% of twin pairs affected by DS, both co-twins were diagnosed with the condition. The adjRR of DS for monozygotic versus singleton pregnancies was 0.34 (95% CI 0.25-0.44) and for dizygotic versus singleton pregnancies 1.34 (95% CI 1.23-1.46). DS fetuses from multiple births were less likely to be prenatally diagnosed than singletons (adjOR 0.62 [95% CI 0.50-0.78]) and following diagnosis less likely to be TOPFA (adjOR 0.40 [95% CI 0.27-0.59]).

CONCLUSIONS: The risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening.

Gestação após gastroplastia para tratamento de obesidade mórbida: série de casos e revisão da literatura

Objetivo: relatar a evolução de uma série de casos de gestação em mulheres previamente submetidas à cirurgia de bypass gástrico para tratamento de obesidade grave. Métodos: cinco casos consecutivos de gravidez após gastroplastia ocorridos entre 2001 e 2004 foram avaliados. As pacientes tinham idade entre 30 e 34 anos e todas haviam sido submetidas à cirurgia de Capella. Aspectos clínicos, laboratoriais e do acompanhamento materno e fetal foram considerados, durante o período gestacional e após o parto. Foi realizada revisão da literatura internacional, por meio das bases de dados MEDLINE e Web of Science, utilizando os seguintes unitermos: gastroplasty, gastric bypass surgery, bariatric surgery e pregnancy. Resultados: todas as gestações observadas foram únicas e não ocorreram complicações obstétricas, durante o seguimento pré-natal e parto. Também não houve registro de recém-nascidos prematuros ou de baixo peso ao nascimento. Conclusão: nossos dados sugerem que a gravidez após gastroplastia é segura para a mãe e feto. Entretanto, em virtude do limitado volume de informação disponível sobre o tema, investigações adicionais são necessárias para estabelecer recomendações apropriadas com relação ao seguimento dessas gestações _________________________________________________ABSTRACT Purpose: we report a small series of pregnant women who underwent gastric bypass surgery for severe obesity, with a review of the literature on this topic. Methods: five consecutive cases of pregnancy after gastroplasty between 2001 and 2004 were evaluated, and clinical, laboratory and therapeutic features were considered. Patients were 30 to 34 years old and all had been submitted to gastroplasty by the Capella technique. The outcomes for both the pregnant woman and the fetus were evaluated. A search of the English language literature was done through MEDLINE and Web of Science databases with the following terms: gastroplasty, gastric bypass surgery, bariatric surgery, and pregnancy. Results: all 5 pregnancies were singleton. No major obstetric complications were observed and there were no premature or lowbirth weight infants. Conclusion: our data suggest that pregnancy following gastroplasty is safe for mother and fetus. However, since information about this topic is limited, further investigations are required to establish appropriate recommendations concerning the follow-up of these pregnancies

Exploring the safety of chemotherapy for treating breast cancer during pregnancy

Introduction: The diagnosis of breast cancer during pregnancy (BCP) represents a unique challenge to the patient, her family and the treating physician. The proper management of this critical clinical situation is crucial, and requires a multidisciplinary approach. A proper understanding of the safety of chemotherapy during pregnancy is a vital step to avoid detrimental consequences on the mother and the fetus.Areas covered: The aim of this article is to review the available evidence on the safety of chemotherapy administration in managing BCP.Expert opinion: The rule of thumb of chemotherapy - avoiding first trimester exposure and starting therapy in the second trimester - can be considered applicable for classic agents that are used in managing pregnant breast cancer patients. Anthracycline-based regimens are considered the standard of care in managing BCP. Recently, a growing amount of data suggests the safety of taxanes during pregnancy. Pregnancy in cancer patients should be considered as "high risk": once the systemic treatment is initiated, regular fetal monitoring is highly recommended. Emerging data are available on the relative long-term safety secondary to anthracycline exposure during pregnancy. A continued monitoring of the health of individuals with prenatal exposure to chemotherapy into adulthood is recommended for the possible occurrence of long-term side effects.

A radiologia dentária na gravidez

Aborda-se a biossegurança aplicada a radiologia dentária relativa à radiação ionizante e a exposição aos agentes biológicos, a que pacientes, grávidas / feto e profissionais são submetidos durante os procedimentos radiológicos. As diferentes doses de radiação emitidas, pelos equipamentos utilizados em radiologia oral, quer nos sistemas analógicos, como digitais. As diversas formas de propagação de micro-organismos, durante a obtenção de imagens radiográficas. As medidas de biossegurança, para prevenção desses riscos em radiologia dentária, através da radioprotecção e do controlo da infeção. A radiação ionizante pela sua elevada energia, é capaz de penetrar na matéria, ionizar os átomos, romper ligações químicas e causar danos nos tecidos biológicos. A exposição a doses elevadas de radiação ionizante pode ainda resultar, na destruição de células ou na indução de cancro. Atualmente a biossegurança em radiologia dentária, tem como principais objetivos, a redução da dose de radiação e evitar a infeção cruzada entre os diferentes agentes envolvidos.