Fetal malformation in a marmoset (Callithrix jacchus): case report

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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.

Glycemic Control in Diabetic Pregnancies: Effects on Fetal and Maternal Outcome

Background: Both maternal and fetal complications are increased in diabetic pregnancies. Although hypertensive complications are increased in pregnant women with pregestational diabetes, reports on hypertensive complications in women with gestational diabetes mellitus (GDM) have been contradictory. Congenital malformations and macrosomia are the main fetal complications in Type 1 diabetic pregnancies, whereas fetal macrosomia and birth trauma but not congenital malformations are increased in GDM pregnancies. Aims: To study the frequency of hypertensive disorders in gestational diabetes mellitus. To evaluate the risk of macrosomia and brachial plexus injury (Erb’s palsy) and the ability of the 2-hour glucose tolerance test (OGTT) combined with the 24-hour glucose profile to distinguish between low and high risks of fetal macrosomia among women with GDM. To evaluate the relationship between glycemic control and the risk of fetal malformations in pregnancies complicated by Type 1 diabetes mellitus. To assess the effect of glycemic control on the occurrence of preeclampsia and pregnancy-induced hypertension in Type 1 diabetic pregnancies. Subjects: A total of 986 women with GDM and 203 women with borderline glucose intolerance (one abnormal value in the OGTT) with a singleton pregancy, 488 pregnant women with Type 1 diabetes (691 pregnancies and 709 offspring), and 1154 pregnant non-diabetic women (1181 pregnancies and 1187 offspring) were investigated. Results: In a prospective study on 81 GDM patients the combined frequency of preeclampsia and PIH was higher than in 327 non-diabetic controls (19.8% vs 6.1%, p<0.001). On the other hand, in 203 women with only one abnormal value in the OGTT, the rate of hypertensive complications did not differ from that of the controls. Both GDM women and those with only one abnormal value in the OGTT had higher pre-pregnancy weights and BMIs than the controls. In a retrospective study involving 385 insulin-treated and 520 diet-treated GDM patients, and 805 non-diabetic control pregnant women, fetal macrosomia occurred more often in the insulin-treated GDM pregnancies (18.2%, p<0.001) than in the diet-treated GDM pregnancies (4.4%), or the control pregnancies (2.2%). The rate of Erb’s palsy in vaginally delivered infants was 2.7% in the insulin-treated group of women and 2.4% in the diet-treated women compared with 0.3% in the controls (p<0.001). The cesarean section rate was more than twice as high (42.3% vs 18.6%) in the insulin-treated GDM patients as in the controls. A major fetal malformation was observed in 30 (4.2%) of the 709 newborn infants in Type 1 diabetic pregnancies and in 10 (1.4%) of the 735 controls (RR 3.1, 95% CI 1.6–6.2). Even women whose levels of HbA1c (normal values less than 5.6%) were only slightly increased in early pregnancy (between 5.6 and 6.8%) had a relative risk of fetal malformation of 3.0 (95% CI 1.2–7.5). Only diabetic patients with a normal HbA1c level (<5.6%) in early pregnancy had the same low risk of fetal malformations as the controls. Preeclampsia was diagnosed in 12.8% and PIH in 11.4% of the 616 Type 1 diabetic women without diabetic nephropathy. The corresponding frequencies among the 854 control women were 2.7% (OR 5.2; 95% CI 3.3–8.4) for preeclampsia and 5.6% (OR 2.2, 95% CI 1.5–3.1) for PIH. Multiple logistic regression analysis indicated that glycemic control, nulliparity, diabetic retinopathy and duration of diabetes were statistically significant independent predictors of preeclampsia. The adjusted odds ratios for preeclampsia were 1.6 (95% CI 1.3–2.0) for each 1%-unit increment in the HbA1c value during the first trimester and 0.6 (95% CI 0.5–0.8) for each 1%-unit decrement during the first half of pregnancy. In contrast, changes in glycemic control during the second half of pregnancy did not alter the risk of preeclampsia. Conclusions: In type 1 diabetic pregnancies it is extremely important to achieve optimal glycemic control before pregnancy and maintain it throughout pregnancy in order to decrease the complication rates both in the mother and in her offspring. The rate of fetal macrosomia and birth trauma in GDM pregnancies, especially in the group of insulin-treated women, is still relatively high. New strategies for screening, diagnosing, and treatment of GDM must be developed in order to decrease fetal and neonatal complications.

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.

Perda e luto: Vivências de mulheres que interromperam a gestação por malformação fetal letal

The scope of this study was to investigate the grieving experiences of women who terminated pregnancies under judicial authorization, due to life-incompatible fetal malformation. Ten women attended in the Fetal Medicine Department of Botucatu Clinical Hospital participated in the study. Data collection was conducted by means of semi-structured interviews forty days after termination. The interviews were recorded and transcribed in full, with the data analyzed from the thematic content analysis perspective. The results revealed that the mothers sought explanations and meanings for the loss, with religious responses and self-blame being very frequent. The reports were marked by feelings of sadness, longing and sensations of emptiness due to the loss of the child, revealing the need of the mothers to dwell on the issue. The mothers were and continued to be linked to their children; the termination of the pregnancy, although being a choice to minimize the pain of an inevitable loss, did not spare the women from experiences of great suffering. The study includes input for the discussion and planning of health approaches and care for women who terminate their pregnancy due to lethal fetal malformation, by means of judicial authorization.

The Molecular Basis of Hydrolethalus Syndrome

Hydrolethalus syndrome (HLS) is a severe fetal malformation syndrome that is inherited by an autosomal recessive manner. HLS belongs to the Finnish disease heritage, an entity of rare diseases that are more prevalent in Finland than in other parts of the world. The phenotypic spectrum of the syndrome is wide and it is characterized by several developmental abnormalities, including hydrocephalus and absent midline structures in the brain, abnormal lobation of the lungs, polydactyly as well as micrognathia and other craniofacial anomalies. Polyhydramnios are relatively frequent during pregnancy. HLS can nowadays be effectively identified by ultrasound scan already at the end of the first trimester of pregnancy. One of the main goals in this study was to identify and characterize the gene defect underlying HLS. The defect was found from a previously unknown gene that was named HYLS1. Identification of the gene defect made it possible to confirm the HLS diagnosis genetically, an aspect that provides valuable information for the families in which a fetus is suspected to have HLS. Neuropathological findings of mutation confirmed HLS cases were described for the first time in detail in this study. Also, detailed general pathological findings were described. Since HYLS1 was an unknown gene with no relatives in the known gene families, many functional studies were performed in order to unravel the function of the gene and of the protein it codes for. Studies showed, for example, that the subcellular localization of the HYLS1 protein was different when the normal and the defective forms were compared. In addition, HYLS1 was shown to possess transactivation potential which was significantly diminished in the defective form. According to the results of this study it can be stated that HYLS1 most likely participates in transcriptional regulation and also in the regulation of cholesterol metabolism and that the function of HYLS1 is critical for normal fetal development.

Mães em UTI neonatal: a experiência da maternidade diante do bebê em situação de risco

Esta pesquisa teve por objetivo compreender as vicissitudes da experiência de tornar-se mãe de um bebê em situação de risco neonatal. Emergiu da experiência da autora no acompanhamento psicológico prestado às mães e familiares de recém-nascidos de alto risco internados em uma Unidade de Terapia Intensiva Neonatal (UTI Neonatal). Foi possível perceber ali que a puérpera que tinha seu filho internado em situação de risco logo após o nascimento vivenciava uma experiência de intenso sofrimento, permeada por conflitos e angústias específicas, tais como: o sentimento de incapacidade pelo parto prematuro e/ou pela malformação fetal, a dor/luto diante da situação de risco e eminência de perda do filho, o medo e a ambivalência na relação afetiva com o bebê. Tais vivências podem representar uma ameaça para a construção do vínculo inicial entre pai/mãe/filho, bem como para a própria saúde psíquica da mulher e do bebê em constituição. Para uma aproximação da experiência subjetiva destas mulheres/mães, optou-se pela pesquisa qualitativa na abordagem psicanalítica. A compreensão do fenômeno foi possibilitada pela análise do discurso das mães que tiveram seus filhos internados na UTI Neonatal, através do método de observação participante dos atendimentos grupais prestados pelo Serviço de Psicologia da instituição, bem como pela análise documental das fichas de acompanhamento psicológico destas mulheres. Participaram do estudo, as mulheres/mães que acompanharam seus filhos internados na UTI Neonatal do Núcleo Perinatal do Hospital Universitário Pedro Ernesto (HUPE), da Universidade do Estado do Rio de Janeiro (UERJ) e que receberam atendimento psicológico grupal: Grupo Mães Presentes durante um período de três meses. A compreensão e interpretação dos aspectos essenciais do fenômeno foram fundamentadas nos pressupostos psicanalíticos da teoria do amadurecimento pessoal de Donald W. Winnicott e em outros autores atuais de referência no campo materno-infantil. Acredita-se que este trabalho servirá de reflexão e contribuição para a construção, na assistência neonatal, de um lugar de acolhimento para a experiência subjetiva dessas mulheres/mães e suas repercussões, a partir de uma perspectiva de cuidado humanizado e integral a saúde, tal como preconizado pelas políticas públicas atuais.

Maternal and perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia in Brazilian women

Objective. To evaluate maternal and perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia (GTN) in Brazilian patients.Methods. This study included 252 subsequent pregnancies after chemotherapy for GTN treated between 1960-2005. Correlations of maternal and perinatal outcomes with chemotherapy regimen (single or multiagent) and the time interval between chemotherapy completion and first subsequent pregnancy were investigated.Results. There was a significant increase in adverse maternal outcomes in women who conceived <6 months than 6-12 months (76.2% and 19.6%; p<0.0001; OR=13.12; CI 95%=3.87-44.40) and >12 months (76.2% and 21.7%; P<0.0001; OR=11.56; CI 95%=3.98-33.55) after chemotherapy. Spontaneous abortion frequency was higher <6 months (71.4%) than 6-12 months (17.6%; p<0.0001: OR=11.66; CI 95%=3.55-38.22) and >12 months (9.4%; p<0.0001: OR=23.97: CI 95%=8.21-69.91) after chemotherapy. There was no difference in adverse perinatal outcomes (stillbirth, fetal malformation, and preterm birth) related to the interval after chemotherapy and Subsequent pregnancy. The overall occurrence of adverse maternal and perinatal outcomes did not significantly differ between patients on single or multiagent regimens.Conclusion. Adverse maternal outcomes and spontaneous abortion were more frequent among patients who conceived within 6 months of chemotherapy completion. In these cases, careful prenatal monitoring and hCG level measurement 6 weeks after the completion of any new pregnancy are recommended. (C) 2008 Elsevier B.V. All rights reserved.

Perfil soroepidemiológico da Rubéola no período pré-vacinal (1989 a 1999) e pós-vacinal (2000 a 2005) de pacientes referenciados ao Instituto Evandro Chagas

A Rubéola é uma virose exantemática geralmente de evolução benigna, mas quando adquirida durante a gestação, pela teratogenicidade do vírus, pode provocar a Síndrome da Rubéola Congênita caracterizada por malformações fetais e aborto espontâneo. Com o objetivo de descrever o perfil soroepidemiológico da Rubéola de pacientes referenciados ao Instituto Evandro Chagas/SVS/MS nos períodos prévacinal(1989 a 1999) e pós-vacinal (2000 a 2005), foi realizado estudo retrospectivo do banco de dados de 34.221 amostras, cujos testes sorológicos foram analisados através da técnica de pesquisa de IgM e IgG por ELISA com kits do laboratório DADE BEHRING^®. A taxa de infecção encontrada foi de 17,2% no período prévacinal e de 4,0% no pós-vacinal. Entre a sintomatologia apresentada no período pré-vacinal, a linfadenopatia teve maior taxa com 38,4% e no pós-vacinal a artralgia com 11,3%. Nas mulheres em idade fértil, a média da taxa de imunes foi de 78,3% e 84,4% no período pré e pós-vacinal, respectivamente. A taxa de infecção em gestantes no período pré-vacinal foi de 9,3% e no pós-vacinal 1,6%. Os recémnascidos infectados corresponderam a 2,1% no período pré e 1,0% no período pósvacinal nesses, houve predomínio de catarata e cardiopatia isoladas ou em associação. Foi concluído que houve diferença significante entre as frequências de todos os segmentos estudados, em relação aos períodos pré e pós-vacinal, confirmando a eficácia da vacina na prevenção da Rubéola e da SRC, tal fato realça a necessidade de se ampliar as coberturas vacinais para impedir a circulação do VR no país, cumprindo assim o acordo de eliminação até o ano 2010.

Sobrepeso e obesidade na gravidez: marcadores bioquímicos e resultados maternos e perinatais

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Cardiac medication during pregnancy, data from the ROPAC

BACKGROUND Data on pharmacological management during pregnancy are scarce. The aim of this study was to describe the type and frequency of cardiac medication used in pregnancy in patients with cardiovascular disease and to assess the relationship between medication use and fetal outcome. METHODS AND RESULTS Between 2007 and 2011 sixty hospitals in 28 countries enrolled 1321 pregnant women. All patients had structural heart disease (congenital 66%, valvular 25% or cardiomyopathy 7% or ischemic 2%). Medication was used by 424 patients (32%) at some time during pregnancy: 22% used beta-blockers, 8% antiplatelet agents, 7% diuretics, 2.8% ACE inhibitors and 0.5% statins. Compared to those who did not take medication, patients taking medication were older, more likely to be parous, have valvular heart disease and were less often in sinus rhythm. The odds ratio of fetal adverse events in users versus non-users of medication was 2.6 (95% CI 2.0-3.4) and after adjustment for cardiac and obstetric parameter was 2.0 (95% CI 1.4-2.7). Babies of patients treated with beta-blockers had a significantly lower adjusted birth weight (3140 versus 3240 g, p = 0.002). The highest rate of fetal malformation was found in patients taking ACE inhibitors (8%). CONCLUSION One third of pregnant women with heart disease used cardiac medication during their pregnancy, which was associated with an increased rate of adverse fetal events. Birth weight was significantly lower in children of patients taking beta-blockers. A randomized trial is needed to distinguish the effects of the medication from the effects of the underlying maternal cardiac condition.

Should valproate be taken during pregnancy?

The Australian Registry of Antiepileptic Drug Use in Pregnancy includes 172 instances in which women took sodium valproate, with or without other antiepileptic drugs, during pregnancy. These pregnancies resulted in a substantially higher (p < 0.05) rate of malformed offspring (15.1%) compared with 348 pregnant women who took antiepileptic drugs other than valproate (2.3%) and 40 pregnancies in epileptic women who took no antiepileptic drugs (2.5%). At valproate doses of 1400 mg and below per day, the mean rate of pregnancies with fetal malformations was 6.42% and did not seem to be dose-dependent. At higher valproate doses, the mean rate of pregnancy with fetal malformation was 33.9% and appeared to increase with increasing drug dosage. This finding suggests the need for reappraisal of the use of valproate in women who may become pregnant or are pregnant whilst the drug is taken. The therapeutic policy adopted may depend on whether valproate doses below 1400 mg per day are regarded as safe for the fetus. This study indicates that the risk of malformation associated with such doses was just statistically significantly (p < 0.05) higher than that associated with other antiepileptic drugs. Various possible clinical scenarios are discussed.

Perfil de citocinas no colostro em função da idade gestacional e do crescimento fetal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Genotoxicity and Fetal Abnormality in Streptozotocin-Induced Diabetic Rats Exposed to Cigarette Smoke Prior to and during Pregnancy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Mixture of vitamin C, hesperidin and piperidol exposure in pregnancy: Maternal-fetal repercussions

To evaluate the reproductive performance and the development of their offspring on rat pregnancy. Wistar pregnant rats were gavaged with 0 mg/kg wb/day (control group, n = 20) and 166.5 mg/kg/day of a mixture of vitamin C, hesperidin and piperidol (experimental group, n = 20) during the organogenic period (from day 5 to 14 of pregnancy; positive vaginal smear = day 0). The female rats were killed on day 21 of pregnancy. The number of implantations, resorptions (dead embryos), and live/dead fetuses were counted for the analysis of the postimplantation loss rates. There was neither alteration in maternal reproductive performance, but it was verified an increase of the number of fetuses presenting dilated urether, hydronephrosis, and reduced ossification of skull due to the treatment of female rats with a mixture of vitamin C, hesperidin and piperidol, these abnormalities were considered transitory and may not interfere on offspring development. It was not verified other type of major malformation neither the appearance of fetuses presenting atrophy of upper limbs that it could be associated to use of this drug.