Determinants of mother-baby relationship evaluated during pregnancy

ABSTRACT Background Mental health promotion is supported by a strong body of knowledge and is a matter of public health with the potential of a large impact on society. Mental health promotion programs should be implemented as soon as possible in life, preferably starting during pregnancy. Programs should focus on malleable determinants, introducing strategies to reduce risk factors or their impact on mother and child, and also on strengthening protective factors to increase resilience. The ambition of early detecting risk situations requires the development and use of tools to assess risk, and the creation of a responsive network of services based in primary health care, especially maternal consultation during pregnancy and the first months of the born child. The number of risk factors and the way they interact and are buffered by protective factors are relevant for the final impact. Maternal-fetal attachment (MFA) is not yet a totally understood and well operationalized concept. Methodological problems limit the comparison of data as many studies used small size samples, had an exploratory character or used different selection criteria and different measures. There is still a lack of studies in high risk populations evaluating the consequences of a weak MFA. Instead, the available studies are not very conclusive, but suggest that social support, anxiety and depression, self-esteem and self-control and sense of coherence are correlated with MFA. MFA is also correlated with health practices during pregnancy, that influence pregnancy and baby outcomes. MFA seems a relevant concept for the future mother baby interaction, but more studies are needed to clarify the concept and its operationalization. Attachment is a strong scientific concept with multiple implications for future child development, personality and relationship with others. Secure attachment is considered an essential basis of good mental health, and promoting mother-baby interaction offers an excellent opportunity to intervention programmes targeted at enhancing mental health and well-being. Understanding the process of attachment and intervening to improve attachment requires a comprehension of more proximal factors, but also a broader approach that assesses the impact of more distal social conditions on attachment and how this social impact is mediated by family functioning and mother-baby interaction. Finally, it is essential to understand how this knowledge could be translated in effective mental health promoting interventions and measures that could reach large populations of pregnant mothers and families. Strengthening emotional availability (EA) seems to be a relevant approach to improve the mother-baby relationship. In this review we have offered evidence suggesting a range of determinants of mother-infant relationship, including age, marital relationship, social disadvantages, migration, parental psychiatric disorders and the situations of abuse or neglect. Based on this theoretical background we constructed a theoretical model that included proximal and distal factors, risk and protective factors, including variables related to the mother, the father, their social support and mother baby interaction from early pregnancy until six months after birth. We selected the Antenatal Psychosocial Health Assessment (ALPHA) for use as an instrument to detect psychosocial risk during pregnancy. Method Ninety two pregnant women were recruited from the Maternal Health Consultation in Primary Health Care (PHC) at Amadora. They had three moments of assessment: at T1 (until 12 weeks of pregnancy) they filed out a questionnaire that included socio-demographic data, ALPHA, Edinburgh post-natal Depression Scale (EDPS), General Health Questionnaire (GHQ) and Sense of Coherence (SOC); at T2 (after the 20th weeks of pregnancy) they answered EDPS, SOC and MFA Scale (MFAS), and finally at T3 (6 months after birth), they repeated EDPS and SOC, and their interaction with their babies was videotaped and later evaluated using EA Scales. A statistical analysis has been done using descriptive statistics, correlation analysis, univariate logistic regression and multiple linear regression. Results The study has increased our knowledge on this particular population living in a multicultural, suburb community. It allow us to identify specific groups with a higher level of psychosocial risk, such as single or divorced women, young couples, mothers with a low level of education and those who are depressed or have a low SOC. The hypothesis that psychosocial risk is directly correlated with MFAS and that MFA is directly correlated with EA was not confirmed, neither the correlation between prenatal psychosocial risk and mother-baby EA. The study identified depression as a relevant risk factor in pregnancy and its higher prevalence in single or divorced women, immigrants and in those who have a higher global psychosocial risk. Depressed women have a poor MFA, and a lower structuring capacity and a higher hostility to their babies. In average, depression seems to reduce among pregnant women in the second part of their pregnancy. The children of immigrant mothers show a lower level of responsiveness to their mothers what could be transmitted through depression, as immigrant mothers have a higher risk of depression in the beginning of pregnancy and six months after birth. Young mothers have a low MFA and are more intrusive. Women who have a higher level of education are more sensitive and their babies showed to be more responsive. Women who are or have been submitted to abuse were found to have a higher level of MFA but their babies are less responsive to them. The study highlights the relevance of SOC as a potential protective factor while it is strongly and negatively related with a wide range of risk factors and mental health outcomes especially depression before, during and after pregnancy. Conclusions ALPHA proved to be a valid, feasible and reliable instrument to Primary Health Care (PHC) that can be used as a total sum score. We could not prove the association between psychosocial risk factors and MFA, neither between MFA and EA, or between psychosocial risk and EA. Depression and SOC seems to have a clear and opposite relevance on this process. Pregnancy can be considered as a maturational process and an opportunity to change, where adaptation processes occur, buffering risk, decreasing depression and increasing SOC. Further research is necessary to better understand interactions between variables and also to clarify a better operationalization of MFA. We recommend the use of ALPHA, SOC and EDPS in early pregnancy as a way of identifying more vulnerable women that will require additional interventions and support in order to decrease risk. At political level we recommend the reinforcement of Immigrant integration and the increment of education in women. We recommend more focus in health care and public health in mental health condition and psychosocial risk of specific groups at high risk. In PHC special attention should be paid to pregnant women who are single or divorced, very young, low educated and to immigrant mothers. This study provides the basis for an intervention programme for this population, that aims to reduce broad spectrum risk factors and to promote Mental Health in women who become pregnant. Health and mental health policies should facilitate the implementation of the suggested measures.

A les��o de isqu��mia/reperfus��o em transplante hep��tico: an��lise gen��tica, morfol��gica e correla����o cl��nica

RESUMO: O transplante hep��tico ortot��pico �� uma terap��utica aceite para casos selecionados de fal��ncia hep��tica terminal. O procedimento tem-�����se aperfei��oado, evidenciado pelo aumento da taxa de sobrevida de 30 para 75% aos 5 anos, mas cerca de 13 a 27% dos enxertos desenvolve fal��ncia prim��ria (PNF) ou disfun����o prim��ria (DF) ap��s o transplante. As consequ��ncias s��o devastadoras para a sobrevida do doente e do enxerto. A sua etiologia �� multifactorial, incluindo factores relacionados com o dador e o receptor, tempos de isqu��mia, agress��es cir��rgicas, bem como caracter��sticas anatomopatol��gicas do enxerto. A les��o de isqu��mia/reperfus��o mantem-�����se como um factor de risco intra operat��rio, com implica����es directas sobre toda a evolu����o do transplante : existe uma rela����o ��ntima entre a PNF e a DF, a preserva����o do enxerto, a les��o de isqu��mia/reperfus��o, e a fal��ncia do transplante. Al��m disso, est�� comprovada evid��ncia que sugere que a les��o de I/R torna um aloenxerto mais vulner��vel por aumento da imunogenicidade, aumentando a probabilidade de epis��dios de rejei����o precoce e tardia. Com base na pr��tica cl��nica quotidiana do CHBPT HCC, estudaram-�����se 54 casos de transplante hep��tico, agrupados segundo grupos por aloca����o do enxerto respectivo: Grupo 1(n=27): dador cad��ver para receptor cirr��tico, Grupo 2 (n=15): dador cad��ver para receptor PAF, Grupo 3 (n=12): dador PAF para receptor cirr��tico. Observaram-�����se as altera����es histol��gicas e moleculares sobre o enxerto at�� ao final da opera����o do receptor, e as suas consequ��ncias cl��nicas,avaliando: -����� As diferentes capacidades de resist��ncia e cada enxerto �� les��o de isqu��mia/reperfus��o. -����� As situa����es em que os factores do receptor se sobrep��em ��s do enxerto na defini����o do progn��stico, e vice versa. -����� A relev��ncia das les��es histol��gicas e moleculares precoces no tecido hep��tico na evolu����o do enxerto e do receptor. Foram colhidas bi��psias por agulha dos 54 enxertos hep��ticos,42 provenientes de cad��ver com cora����o batente(morte cerebral) e 12 provenientes de dador vivo com PAF, em tr��s tempos diferentes do processo de colheita e transplante hep��tico: ����� A primeira(T0)antes da clampagem da aorta do dador -����� A segunda (T1) no final da isqu��mia fria -����� A terceira (T2) ap��s a reperfus��o do enxerto, durante o encerramento da parede abdominal. A estas amostras foi extra��do RNA total, convertido em cDNA por transcri����o reversa e feita a an��lise da express��o dos genes da CTLA4, IL-�����1��, IL-�����4, IL-�����6, IL-�����13, TNF-�������, Perforina, Selectina, (SELE), Fas-�����ligando, Granzima-�����B, Heme-�����Oxigenase 1(HO1)e ��xido N��trico Sintetase(iNOS2A)por PCR quantitativo segundo o m��todo do Ct comparativo, utilizando como refer��ncia a express��o dos genes da amostra n��o-�����isqu��mica ���T0. Os fragmentos de todas as bi��psias foram seccionados, para envio de amostra comparativa para processamento histol��gico habitual, sem qualquer altera����o ao protocolo seguido habitualmente na Unidade de Transplanta����o do Hospital Curry Cabral. A presen��a de alguns par��metros histol��gicos definidos, como esteatose, necrose, vacuoliza����o, congest��o sinusoidal e infiltra����o neutrof��lica, foi registada e contabilizada numa classifica����o num��rica. O seguimento cl��nico e laboratorial, bem como o acompanhamento de eventuais complica����es, foi registado e correlacionado com os dados das colheitas de ��rg��os e com os dados das bi��psias. Foram consideradas as seguintes vari��veis, como as mais relevantes e objectivas para a interpreta����o da evolu����o cl��nica, tendo sido comparadas estatisticamente com os dados recolhidos, laboratoriais e cl��nicos: disfun����o do enxerto, 207 p��s operat��rias, n��mero de internamentos igual ou superior a 2 e rejei����o cr��nica e/ou morte do receptor. Foram identificadas caracter��sticas cl��nicas menos favor��veis, a considerar, nalgumas circunst��ncias: g��nero feminino do receptor (sobretudo associado a enxerto masculino, p=0,077), isqu��mia fria superior a 500 minutos (p=0,074), isqu��mia quente superior a 90 minutos (p=0,099). Na an��lise laboratorial, distinguiram-�����se duas caracter��sticas histol��gicas desfavor��veis e irrevers��veis, como ��ndice de mau progn��stico: a necrose e a baloniza����o (p=0,029); no painel gen��tico escolhido neste estudo,a express��o basal de IL-�����1��(p=0,028), de SELE p=0,013)e de FAS-�����L (p=0,079)relacionaram-�����se com pior progn��stico. Algumas caracter��sticas protectoras intr��nsecas dos enxertos s�� se revelaram indirectamente, como menor infiltra����o neutrof��lica e maior express��o de HO1 e de iNOS nos enxertos PAF, n��o tendo sido poss��vel provar uma interfer��ncia directa nos resultados cl��nicos. N��o se obteve express��o mensur��vel de genes anti-����� inflamat��rios nas biopsias hep��ticas processadas neste estudo, como a IL13 e a I 4: assim, com a metodologia utilizada, n��o foi poss��vel obter um perfil de express��o gen��tica associado a boa evolu����o cl��nica. O perfil inverso foi sugerido apenas pela express��o basal dos 3 genes mencionados (FAS-�����L,IL-�����1�� e SELE)no mesmo painel, com o protocolo seguido neste conjunto de 54 doentes. As caracter��sticas do receptor sobrepuseram-�����se ��s do enxerto no caso de: -����� diagn��stico de PAF no receptor, que determinou uma maior predisposi����o para a disfun����o do enxerto, o que, por sua vez, determina uma menor sobrevida. No entanto, o diagn��stico de PAF no receptor exibe uma curva de sobrevida mais favor��vel. -����� receptores com um baixo balan��o de risco (BAR)definiram caracter��sticas favor��veis para enxertos com n��veis baixos e moderados de esteatose, fazendo que esta caracter��stica, definida como um risco acrescido, n��o s�� n��o se manifestasse clinicamente,como parecesse um factor favor��vel. As caracter��sticas do enxerto sobrepuseram-�����se ��s do receptor no caso de: -����� tempo de isqu��mia fria superior a 500 minutos -����� baloniza����o, necrose, FAS-�����L,IL-�����1�� e SELE em T0 A integra����o dos resultados moleculares e morfol��gicos com a evolu����o cl��nica, real��a o papel da mobiliza����o precoce de neutr��filos nos desempenhos menos favor��veis do enxerto hep��tico. -------------ABSTRACT: Orthotopic liver transplantation is na accepted therapeutic procedure for selected cases of terminal liver failure. The procedure has been improved, evidenced by the rise of survival rates from 30 to 70% at 5 years, but 13 to 27% of the liver grafts develops primary non function (PNF) or primary dysfunction (PDF) after transplantation. The consequences are devastating for the survival of the patient and of the graft. Its etiology is multifactorial, including factos related with the donor and with the recipient, ischemic times, surgical aggressions, as well as the histological characteristics of the graft. The ischemia/reperfusion lesion is still an intraoperative risk factor, with direct implications in the whole transplant outcome: there is a close interrelation between PNF and DF, graft preservation, ischemia / reperfusion lesion and graft failure. Beyond his, there is proved evidence that suggests that I/R lesion turns the allograft more vulnerable by increasing its immunogenity, increasing the probability of precocious and late rejection episodes. Based on the daily clinical practice at CHBPT /HCC, 54 cases of hepatic transplantation have been studied, grouped by allocation of each graft: Group (n=27):deceased do nortocirrhotic recipient, Group 2 (n=15): deceased donor to FAP recipient, Group 3 (n=12): FAP living donor to cirrhotic recipient. The histologic and molecular changes in the liver graft were observed until the end of the recipiente operation,together with its clinical consequences, evaluating:-�����The different capacity of resistance of each graft to the ischemia / reperfusion lesion -����� The situations where the recipiente factos overlap the ones of the graft, in the definition of prognosis, and vice versa.-����� The relevance of the precocious histologic and molecular lesions of the hepatic tissue in the clinical outcome of the graft and the recipient. Needle biopsies were obtained from 54 liver grafts, 42 deceased brain dead donors and 12 from FAP living donors, at three diferente times of the harvesting and the hepatic transplantation: The first one (T0) before clamping the donor aorta -����� The second one (T2) in the end of cold ischemia time -����� The third one (T) after the reperfusion of the graft, during the closure of the abdominal wall. Total RNAwas extracted to these samples, converted to cDNA by reverse transcription and the analysis of gene expression was made for CTLA4,IL-�����1��,IL-�����4,IL-�����6,IL-�����13,TNF-�������,Perforin,E Selectin (SELE),Fas-�����ligand,Granzyme-�����B,Heme-�����oxigenase 1 (HO1) and Nitric Oxide Sintetase (iNOS2A) by quantitative PCR, according with the Ct comparative method, using the expression of the non ischemic sample ��� T0. The fragments of all the biopsies were divided, to send a comparative sample to the usual histologic processement, keeping the same usual protocol at the Transplantation Unit of Curry Cabral Hospital. The presence of some defined histologic parameters, such as steatosis, necrosis, vacuolization, sinusoidal congestion and neutrophilic infiltration, was registered and catalogued in a numeric classification. The clinical and laboratory follow-�����up, as well as the following of eventual complications, was registered and correlated with the data from organ procurement operations and with the data from the biopsies. The following variables were considered as the most relevant and objective ones, to the interpretation of the clinical evolution, being statistically compared with the clinical and laboratorial collected data: graft dysfunction, post-�����operative complications, number of readmissions of 2 or more and chronic rejection and /or recipiente death. There were identified some unfavorable clinical characteristics, to be considered under certain circumstances: recipiente female gender (specially associated with malegraft, p=0,077), cold ischemia time of more than 500 minutes (p=0,074), warm ischemia time of more than 90 minutes (p=0,099). In the laboratory analysis, two histologic characteristics were identified as unfavorable and irreversible, associated with bad prognosis: necrosis and balonization (p=0,029); in the gene panel selected in this study, the basal expression of IL-�����1�� (p=0,028), SELE (p=0,013) and FAS-�����L (p=0,079)were related with worse prognosis.Some intrinsic protective characteristics of the grafts were only indirectly revealed, such as less neutrophilic infiltration and bigger expression of HO1 and iNOS in FAP grafts, being impossible to prove any direct inte ference in the clinical results. A relevant and measurable expression of the anti inflammatory genes IL13 and IL4 was not obtained: with the used methodology, it was impossible to obtain a gene expression profile associated with a favorable clinical outcome.The inverse profile was suggested only by the basal expression of the three mentioned genes (FAS-�����L, IL-����� 1�� e SELE) in the same gene panel, according with the followed protocol in this group of 54 patients. The characteristics of the recipient overlapped those from the graft, in the case of :-����� FAP diagnosis in the recipient, which determined a bigger predisposition to graft dysfunction, which by itself determines a shorter survival. However, FAP diagnosis in the recipiente depicts a more favorable survival curve. -����� Recipients with a low balance risk ��ndex (BAR) defined favorable characteristics to grafts with low and moderate grades of steatosis, making that this characteristic, associated with bad prognosis, looked like a favorable factor, and with no clinical interference. The graft characteristics overlapped those from the receptor in the case of: -����� Cold ischemic time more than 500 minutes -����� Balonization, necrosis, FAS-�����L, IL-�����1�� and SELE at T0. The integration of molecular and morphologic results with the clinical evolution, stresses the role of a precocious neutrophils mobilization in the worse outcomes of liver grafts.

Varia����o temporal da protoporfirina-zinco PPZ em trabalhadores expostos a chumbo

RESUMO - O doseamento da protoporfirina-zinco (PPZ) vem sendo preconizado como indicador a utilizar em primeira linha nos programas de monitoriza����o biol��gica da exposi����o profissional a chumbo. A PPZ apresenta um elevado grau de associa����o com a plumbemia e representa, num dado momento, o efeito metab��lico do chumbo sobre a ferro- -quelatase (enzima catalisadora da incorpora����o do ferro na protoporfirina IX) ao longo dos anteriores cerca de tr��s meses. Num estudo incidindo sobre 67 trabalhadores expostos a chumbo, do sexo masculino, os autores avaliaram a varia����o da PPZ em rela����o �� plumbemia determinada num determinado momento (t0) e em sucessivos doseamentos efectuados cerca de 30 (t1), 60 (t2) e 90 (t3) dias ap��s esse momento. Da an��lise dos resultados obtidos conclui-se que em trabalhadores expostos a chumbo de modo considerado est��vel (com n��veis de Pb-S entre 30 e 78 ��g/dL) a PPZ n��o variou significativamente ao longo do per��odo de tempo considerado. Deste modo, parece poder concluir-se que os resultados de PPZ s��o representativos do n��vel de exposi����o (inferida pelos n��veis de dose interna) pelo menos em rela����o ao per��odo de cerca de tr��s meses anteriores, correspondendo �� resposta org��nica consequente �� dose em causa.