Variations in Management of Mild Prenatal Hydronephrosis Among Maternal-Fetal Medicine Obstetricians, and Pediatric Urologists and Radiologists

Purpose: There are no current guidelines for diagnosing and managing mild prenatal hydronephrosis. Variations in physician approach make it difficult to analyze outcomes and establish optimal management. We determined the variability of diagnostic approach and management regarding prenatal hydronephrosis among maternal-fetal medicine obstetricians, pediatric urologists and pediatric radiologists. Materials and Methods: Online surveys were sent to mailing lists for national societies for each specialty. Participants were surveyed regarding criteria for diagnosing mild prenatal hydronephrosis and recommendations for postnatal management, including use of antibiotic prophylaxis, followup scheduling and type of followup imaging. Results: A total of 308 maternal-fetal medicine obstetricians, 126 pediatric urologists and 112 pediatric radiologists responded. Pediatric urologists and radiologists were divided between Society for Fetal Urology criteria and use of anteroposterior pelvic diameter for diagnosis, while maternal-fetal medicine obstetricians preferred using the latter. For postnatal evaluation radiologists preferred using personal criteria, while urologists preferred using anteroposterior pelvic diameter or Society for Fetal Urology grading system. There was wide variation in the use of antibiotic prophylaxis among pediatric urologists. Regarding the use of voiding cystourethrography/radionuclide cystography in patients with prenatal hydronephrosis, neither urologists nor radiologists were consistent in their recommendations. Finally, there was no agreement on length of followup for mild prenatal hydronephrosis. Conclusions: We observed a lack of uniformity regarding grading criteria in diagnosing hydronephrosis prenatally and postnatally among maternal-fetal medicine obstetricians, pediatric urologists and pediatric radiologists. There was also a lack of agreement on the management of mild intermittent prenatal hydronephrosis, resulting in these cases being managed inconsistently. A unified set of guidelines for diagnosis, evaluation and management of mild intermittent prenatal hydronephrosis would allow more effective evaluation of outcomes.

Calcium channel TRPV6 is involved in murine maternal-fetal calcium transport

Maternal-fetal calcium (Ca(2+)) transport is crucial for fetal Ca(2+) homeostasis and bone mineralization. In this study, the physiological significance of the transient receptor potential, vanilloid 6 (TRPV6) Ca(2+) channel in maternal-fetal Ca(2+) transport was investigated using Trpv6 knockout mice. The Ca(2+) concentration in fetal blood and amniotic fluid was significantly lower in Trpv6 knockout fetuses than in wildtypes. The transport activity of radioactive Ca(2+) ((45)Ca) from mother to fetuses was 40% lower in Trpv6 knockout fetuses than in wildtypes. The ash weight was also lower in Trpv6 knockout fetuses compared with wildtype fetuses. TRPV6 mRNA and protein were mainly localized in intraplacental yolk sac and the visceral layer of extraplacental yolk sac, which are thought to be the places for maternal-fetal Ca(2+) transport in mice. These expression sites were co-localized with calbindin D(9K) in the yolk sac. In wildtype mice, placental TRPV6 mRNA increased 14-fold during the last 4 days of gestation, which coincides with fetal bone mineralization. These results provide the first in vivo evidence that TRPV6 is involved in maternal-fetal Ca(2+) transport. We propose that TRPV6 functions as a Ca(2+) entry pathway, which is critical for fetal Ca(2+) homeostasis.

Maternal, fetal, and infant nutrition, 1973<[-1974] >. Hearings, Ninety-third Congress, first[-second] session ...

"Series 73/MFI1<-4 >

The v-MFG test: Investigating maternal, offspring and maternal-fetal genetic incompatibility effects on disease and viability

The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.

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.

Protein deficiency and nutritional recovery modulate insulin secretion and the early steps of insulin action in rats

Maternal malnutrition was shown to affect early growth and leads to permanent alterations in insulin secretion and sensitivity of offspring. In addition, epidemiological studies showed an association between low birth weight and glucose intolerance in adult life. To understand these interactions better, we investigated the insulin secretion by isolated islets and the early events related to insulin action in the hind-limb muscle of adult rats fed a diet of 17% protein (control) or 6% protein [low (LP) protein] during fetal life, suckling and after weaning, and in rats receiving 6% protein during fetal life and suckling followed by a 17% protein diet after weaning (recovered). The basal and maximal insulin secretion by islets from rats fed LP diet and the basal release by islets from recovered rats were significantly lower than that of control rats. The dose-response curves to glucose of islets from LP and recovered groups were shifted to the right compared to control islets, with the half-maximal response (EC 50) occurring at 16.9 ± 1.3, 12.4 ± 0.5 and 8.4 ± 0.1 mmol/L, respectively. The levels of insulin receptor, as well as insulin receptor substrate-1 and phosphorylation and the association between insulin receptor substrate-1 and phosphatidylinositol 3-kinase were greater in rats fed a LP diet than in control rats. In recovered rats, these variables were not significantly different from those of the other two groups. These results suggest that glucose homeostasis is maintained in LP and recovered rats by an increased sensitivity to insulin as a result of alterations in the early steps of the insulin signal transduction pathway.

The detrimental role of angiotensin receptor agonistic autoantibodies in intrauterine growth restriction seen in preeclampsia.

Growth-restricted fetuses are at risk for a variety of lifelong medical conditions. Preeclampsia, a life-threatening hypertensive disorder of pregnancy, is associated with fetuses who suffer from intrauterine growth restriction (IUGR). Recently, emerging evidence indicates that preeclamptic women harbor AT(1) receptor agonistic autoantibodies (AT(1)-AAs) that contribute to the disease features. However, the exact role of AT(1)-AAs in IUGR and the underlying mechanisms have not been identified. We report that these autoantibodies are present in the cord blood of women with preeclampsia and retain the ability to activate AT(1) receptors. Using an autoantibody-induced animal model of preeclampsia, we show that AT(1)-AAs cross the mouse placenta, enter fetal circulation, and lead to small fetuses with organ growth retardation. AT(1)-AAs also induce apoptosis in the placentas of pregnant mice, human villous explants, and human trophoblast cells. Finally, autoantibody-induced IUGR and placental apoptosis are diminished by either losartan or an autoantibody-neutralizing peptide. Thus, these studies identify AT(1)-AA as a novel causative factor of preeclampsia-associated IUGR and offer two possible underlying mechanisms: a direct detrimental effect on fetal development by crossing the placenta and entering fetal circulation, and indirectly through AT(1)-AA-induced placental damage. Our findings highlight AT(1)-AAs as important therapeutic targets.

Neonatally Induced Mild Diabetes in Rats and Its Effect on Maternal, Placental, and Fetal Parameters

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

EFFECT OF EXERCISE DURING PREGNANCY AND DAM AGE ON MATERNAL BLOOD-CHEMISTRY AND FETAL GROWTH

In order to determine the effect of maternal exercise on maternal nutritional status and fetal growth, young (Y = 45-50 days old) Wistar rats were divided into 4 groups of 5 to 8 animals: control pregnant (CP), control non-pregnant (CNP), exercise-trained (swimming 1 h/day, 5 days/week, for 19 days) pregnant (TP) and exercise-trained non-pregnant (TNP). Four equivalent groups of adult rats (A - 90-100 days old) were also formed. Serum glucose, total protein, albumin, hematocrit and liver glycogen were determined in female rats and pups. There were no statistical differences in serum glucose, total protein and albumin levels, litter size ot birth weight among exercise-trained animals, controls and their respective pups. Hematocrit was significantly lower in pups of exercise-trained young rats than in all other groups (YCP = 38.6 +/- 3.0; YTP = 32.6 +/- 2.1; ACP = 39.0 +/- 2.5; ATP = 39.2 +/- 2.9%). Liver glycogen levels were lower in pregnant than in non-pregnant rats but similar in exercise-trained and control rats of the same age and physiological status (YCNP = 4.1 +/- 0.2; YCP = 2.7 +/- 0.9; YTNP = 4.9 +/- 0.8; YTP = 2.7 +/-0.4; ACNP = 6.1 +/- 0.6; ACP = 3.1 +/- 0.8; ATNP = 6.6 +/- 0.8; ATP = 2.2 +/- 0.9 mg/100 mg). We conclude that pups of adult female rats are spared from the effects of this kind of exercise training during pregnancy. on the other hand, it appears that maternal adaptations to exercise training in young rats are able to preserve only some aspects of pup metabolism.

Effect of himatanthus sucuuba in maternal reproductive outcome and fetal anomaly frequency in rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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.

O que os olhos veem, o coração sente: estudo sobre a detecção de malformação fetal na experiência de gestantes na Bahia.

Esta tese discute o impacto do Diagnóstico de Malformação fetal na experiência das gestantes usuárias do SUS na Bahia, destacando as noções de dia-gnosis e pro-gnosis desenvolvidas por Gross e Shuval (2008) de forma associada à medicina do risco no encontro médico-paciente. Destaca o discurso biomédico na formatação diagnóstica, as diferentes percepções de risco e o forte engajamento das usuárias frente às tecnologias pré-natais e intervenções cirúrgicas neonatais, caucionado na esperança de que o avanço da ciência seja capaz de reverter ou abrandar a condição do seu feto/bebê. È diante da responsabilização da mulher por não ter produzido um feto/bebê saudável, mas um feto/bebê malformado, que se observa a prevalência de normas culturais e de gênero que conferem à maternidade um lugar de autossacrificio, de dedicação e criação dos filhos, como também status social O espaço pré-natal é marcado pela ausência de discussão a respeito do prognóstico de tais condições, com a consequente busca pelas gestantes do conhecimento por meio da internet, da opinião do marido e da crença religiosa que servem de alicerce para lidar com a antecipação da deficiência. As gestantes acreditam ser este um desígnio de Deus, uma espécie de provação e uma prova de amor incondicional ao futuro filho com deficiência (que poderá ou não sobreviver). A maioria das gestantes, 20 entrevistadas, prefere, contudo, ter um filho com deficiência do que sofrer sua perda. Em outra vertente, a tese analisa a forma como se organiza o sistema de saúde quanto à detecção de uma malformação congênita, apontando a precariedade da rede de atenção básica quanto à qualificação dos profissionais e o devido encaminhamento referente ao serviço especializado. A tecnologia de visualização o ultrassom obstétrico é a primordial ferramenta para detecção de alguma alteração fetal, porém somente ocorre o esclarecimento do diagnóstico de malformação fetal no serviço público de referência em medicina fetal em Salvador, Bahia. Destaca-se a falta de uma política pública do Ministério da Saúde que norteie o desenvolvimento da medicina fetal no Brasil, haja vista os diferentes impactos diante das tecnologias de inovação em saúde que geram vulnerabilidades e desigualdades sociais. Enfatiza-se a necessidade de uma revisão quanto à regulamentação do uso do ultrassom obstétrico que impeça o uso abusivo ou sua omissão diante dos crescentes casos de anomalias congênitas.

Fetal Umbilical Artery Doppler Pulsatility Index as a Predictor of Cardiovascular Risk Factors in Children - A Long-Term Follow Up Study

Abstract Objective To determine if high umbilical artery Doppler (UAD) pulsatility index (PI) is associated with cardio-vascular (CV) risk-factors in children at age 12 years. Methods We studied 195 children at age 12 years who had had in-utero UAD studies performed at 28 weeks gestation. The children were grouped according to whether their umbilical Doppler PI was high (indicating poor feto-placental circulation) or normal. At age 12 years we assessed CV risk factors, including anthropometric measures, blood pressure, pulse wave velocity (a measure of arterial compliance), cardio-respiratory fitness and homocysteine and cholesterol serum levels. Results Compared with children with a normal UAD PI (N=88), the children (N=107) with high UAD PI had higher resting pulse rate (p=0.04), higher pulse wave velocity (p=0.046), higher serum homocysteine levels (p=0.032) and reduced arterial compliance (7.58 v 8.50 m/sec, p=0.029) using univariate analysis. These differences were not present when adjusting for cofounders was modelled. Conclusion High PI on UAD testing in-utero may be associated with increased likelihood of some cardio-vascular risk factors at age 12-years but confounding variables may be as important. Our study raises possible long-term benefits of in-utero UAD measurements.

Maternal diabetes affects specific extracellular matrix components during placentation

During embryo implantation, invasive trophoblast cells mediate embryo invasion into the decidualized stroma, forming a rich network of lacunae that connect the embryonic tissues to the maternal blood vessels. Placentation is probably guided by the composition and organization of the endometrial extracellular matrix. Certain pathological conditions that occur during pregnancy, including diabetes, have been linked to abnormal placental morphology and consequent fetal morbidity. We used immunoperoxidase techniques to identify members of the collagen, proteoglycan and glycoprotein families in the various compartments of the rat placenta and to determine whether experimentally induced diabetes affects placental morphology and alters the distribution of these molecules during pregnancy. Single injections of alloxan (40 mg kg(-1) i.v.) were used to induce diabetes on day 2 of pregnancy in Wistar rats. Placentas were collected on days 14, 17, and 20. Type I and III collagen, as well as the proteoglycans decorin and biglycan, were found to be distributed throughout the placentas of control and diabetic rats. In both groups, laminin expression decreased at the end of pregnancy. In contrast, fibronectin was detected in the labyrinth region of diabetic rats at all gestational stages studied, whereas it was detected only at term pregnancy in the placentas of control rats. These results show for the first time that some extracellular matrix molecules are modulated during placental development. However, as diabetic rats presented increased fibronectin deposition exclusively in the labyrinth region, we speculate that diabetes alters the microenvironment at the maternal-fetal interface, leading to developmental abnormalities in the offspring.

Placentation in the paca (Agouti paca L)

Background: the paca is a South American rodent with potential as a commercial food animal. We examined paca placenta as part of a wider effort to understand the reproductive biology of this species.Methods: Thirteen specimens between midgestation and term of pregnancy were studied by light and transmission electron microscopy.Results: the placenta is divided into several lobes separated by interlobular trophoblast. Maternal arterial channels and fetal veins are found at the centre of each lobe. In the labyrinth, maternal blood flows through trophoblast-lined lacunae in close proximity to the fetal capillaries. The interhaemal barrier is of the haemomonochorial type with a single layer of syncytiotrophoblast. Caveolae occur in the apical membrane of the syncytiotrophoblast and recesses in the basal membrane, but there is no evidence of transtrophoblastic channels. The interlobular areas consist of cords of syncytiotrophoblast defining maternal blood channels that drain the labyrinth. Yolk sac endoderm covers much of the fetal surface of the placenta. The subplacenta comprises cytotrophoblast and syncytiotrophoblast. There are dilated intercellular spaces between the cytotrophoblasts and lacunae lined by syncytiotrophoblast. In the junctional zone between subplacenta and decidua, there are nests of multinucleated giant cells with vacuolated cytoplasm. The entire placenta rests on a pedicle of maternal tissue. An inverted yolk sac placenta is also present. The presence of small vesicles and tubules in the apical membrane of the yolk sac endoderm and larger vesicles in the supranuclear region suggest that the yolk sac placenta participates in maternal-fetal transfer of protein.Conclusion: the paca placenta closely resembles that of other hystricomorph rodents. The lobulated structure allows for a larger exchange area and the development of precocial young.