Preeclampsia is a placental-related disorder characterized by generalized endothelial activation. Vascular predisposition is associated with the occurrence of preeclampsia and the recurrence risk is substantial. Onset of preeclampsia is preceded by placental hypo-perfusion, and placental over-production of vasoconstrictive agents might explain symptoms such as hypertension and proteinuria. Preeclampsia is associated with the birth of small-for-gestational-age (SGA) infants. The trajectory of postnatal growth in SGA-born children is described as catch-up, but it is unclear whether prenatal preeclampsia is independently associated with postnatal growth. The objectives were: firstly, to study the association between partner change and prior miscarriages on the occurrence of preeclampsia and SGA; secondly, to study postnatal growth in children prenatally exposed to preeclampsia; and thirdly, to address the association between blood pressure (BP) changes during pregnancy and risks of preeclampsia and SGA. Population-based cohort studies were performed with information from the following registers: Swedish Medical Birth Register, Uppsala Mother and Child Database and Stockholm-Gotland Obstetric Database. Associations were estimated with logistic and linear regression analyses, with adjustments for maternal characteristics, including body mass index, pre-gestational diseases and socioeconomic factors. The results were, firstly, that partner change was associated with preeclampsia and SGA birth in the second pregnancy but depended on the outcome of the first pregnancy, and that a history of recurrent miscarriages was associated with increased risks of preeclampsia and SGA. Secondly, prenatal exposure to preeclampsia was associated with increased offspring growth in height during the first five years. This association was also seen in children born with normal birth weight for gestational age. Thirdly, pre-hypertension in late gestation and elevated diastolic BP from early to mid-gestation were both associated with SGA birth. Further, women with pre-hypertension in early gestation without lowered diastolic BP until mid-gestation seemed to represent a risk group for preeclampsia. To conclude, the importance of previous pregnancy outcomes in the antenatal risk evaluation was highlighted. Secondly, the results imply that postnatal growth trajectory is related to maternal preeclampsia, in addition to SGA. Thirdly, the association between BP changes within a normal range and SGA may challenge the clinical cut-off for hypertension in pregnancy.

Diversos estudos observaram uma correlação entre doenças na idade adulta e o ambiente durante a vida fetal. O estudo realizado por Barker e colaboradores foi um dos primeiros a relatar a hipótese de um possível envolvimento do ambiente intra-uterino com o desenvolvimento de doenças cardiovasculares, mas os mecanismos responsáveis por esta associação ainda não são totalmente conhecidos. Estudos demonstraram uma associação entre baixo peso ao nascimento com resistência à insulina e intolerância à glicose na vida adulta. Recentemente, verificamos que o consumo de dieta hipossódica, conhecido modelo de resistência à insulina, durante a gestação e lactação está vinculado a menor sensibilidade à insulina na prole adulta. Visto que a presença de resistência à insulina durante a gestação leva a diversas alterações metabólicas na prole adulta, pode-se supor que a sobrecarga de sacarose, um modelo de resistência à insulina, durante a gestação e lactação influencie no desenvolvimento da prole. Assim, o objetivo do presente estudo foi verificar a repercussão da resistência à insulina, durante a gestação sobre a prole adulta. Para tanto, ratas Wistar foram alimentadas com dieta hipo (HO) ou normossódica (NR) suplementadas ou não com sacarose (NR+SAC - 20g/dL) ou maltodextrina (NR+MALTO - 20g/dL) desde a oitava semana de vida até o final da gestação e amamentação. Na prole resultante destes animais foi observado menor peso ao nascimento nos grupos HO, NR+SAC e NR+MALTO. Esta alteração resultou no desenvolvimento de maior insulinemia, pressão arterial e maior captação de glicose na prole de fêmeas das mães do grupo NR+SAC. Os machos apresentaram menor índice de adiposidade e maior expressão gênica renal dos componentes do sistema renina-angiotensina. Tais resultados nos permitem concluir que a sobrecarga de carboidratos durante a gestação e lactação está associada a alterações no peso ao nascimento e no metabolismo da insulina na idade adulta. É possível que a ativação do sistema renina-angiotensina materno induzido pela sobrecarga de carboidrato esteja associada a alterações deste mesmo sistema observado na prole adulta. / Many studies observed a correlation between diseases in adult subjects and the environment during the fetal life. Barker and coworkers hypothesized that there is a possible intrauterine enviroment association with cardiovascular diseases in adulthood. The mechanisms responsible for this association are still not very well known. Recently, we have verified that low-salt diet consumption, a well-known model of insulin resistance, during pregnancy and lactation is associated with a lower insulin sensitivity in the adult offspring. Since insulin resistance during pregnancy leads to many metabolic alterations in the adult offspring, we suppose that sucrose overload during pregnancy and lactation could influence the offspring development. The aim of this study was to verify the effects on adult offspring of insulin resistance during pregnancy and lactation. Female Wistar rats were fed low (LSD) and normal-salt diet (NSD) supplemented or not with sucrose (SUC - 20 g/dL) or maltodextrin (MALTO - 20 g/dL) until the end of pregnancy and lactation. Lower birth weight was observed in offspring of LSD, SUC and MALTO groups. Higher plasma insulin level, blood pressure and glucose uptake was detected in the adult SUC female offspring. SUC male offspring had lower adiposity index and higher gene expression of the renal renin-angiotensin components. These results show that carbohydrate overload during pregnancy and lactation is associated with alterations in birth weight and in insulin metabolism at adult life. It is possible that the maternal renin-angiotensin system activation by the carbohydrate overload is associated with alterations in the same system observed in the adult offspring.

<p><font face="Times New Roman" size="3"><font face="Times New Roman" size="3"> <p align="left">The study made use of cross-sectional design that compared the performance of younger children (6- to 7-year-olds) with that of older children (12- to 13-year-olds) on various measures of executive function. Within this, it made use of a natural experimental design, with children exposed to alcohol<i><font face="Times New Roman" size="3"> as the experimental group and non-exposed children as the control group.</font></i></p> </font></font></p>

Although the association between high maternal alcohol consumption and adverse reproductive outcomes is well established, the effect of lower levels of consumption during pregnancy is unclear; few studies have investigated this exposure. A hospital-based case-control study of small-for-gestational age (SGA) newborns (birth weight below the 10th percentile, according national standards for gestational age and sex) was conducted in Montreal between 1998 and 2000. Controls were born at the same hospital and during the same period with birth weight at or above the 10th percentile. This analysis aims at investigating the effect of low alcohol consumption (0.25 to 3 alcoholic drinks weekly) during pregnancy on the risk of small-for-gestational-age (SGA) birth. Independent effects of wine, beer and spirits and of paternal alcohol consumption before conception were also assessed. The logistic regression analysis showed no significant effect of light maternal drinking during pregnancy on the risk of SGA birth. The association was also studied separately for consumption of wine, beer and spirits, and likewise for paternal alcohol consumption, with similarly negative results.

<p><font face="Times New Roman" size="3"><font face="Times New Roman" size="3"> <p align="left">The study made use of cross-sectional design that compared the performance of younger children (6- to 7-year-olds) with that of older children (12- to 13-year-olds) on various measures of executive function. Within this, it made use of a natural experimental design, with children exposed to alcohol<i><font face="Times New Roman" size="3"> as the experimental group and non-exposed children as the control group.</font></i></p> </font></font></p>

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Le bisphénol A (BPA) présente des propriétés perturbatrices thyroïdiennes. Compte-tenu du rôle essentiel du système thyroïdien sur le développement du système nerveux central, l'exposition de la femme enceinte au bisphénol A est très préoccupante. Ainsi, cette thèse visait à déterminer les conséquences d'une exposition gestationnelle au BPA sur le développement du SNC conjointement aux effets sur la fonction thyroïdienne dans un contexte d'exposition interne parfaitement documenté et évalué par rapport aux expositions décrites chez l'être humain. L'exposition de brebis gestantes au BPA perturbait l'homéostasie thyroïdienne maternelle et modulait chez le fœtus, le métabolome de différentes structures cérébrales. Les modulations observées suggéraient que le BPA pouvait altérer la neurogenèse, la plasticité neuronale, la structure membranaire et le métabolisme énergétique au niveau central. La dose induisant les perturbations de la fonction thyroïdienne maternelle et du système nerveux central fœtal conduisait à des concentrations sériques en BPA similaires à celles décrites chez l'homme. / Bisphenol A (BPA) is able to disturb the thyroid function. Given the key role of thyroid function in the development of the central nervous system (CNS), gestational exposure to BPA is a matter of particular concern. Our goal was to evaluate the consequences of a BPA gestational exposure on the developing CNS jointly to its effects on the thyroid function within a context of a well-documented internal exposure compared to BPA human exposure. BPA exposure of pregnant ewes disrupted the maternal thyroid homeostasis and modulated the metabolome of specific fetal brain regions. The different modulations we observed suggested that BPA might alter neurogenesis, neuronal plasticity, membrane structure and energy metabolism. Interestingly, the BPA dose inducing maternal thyroid disruption and fetal CNS modulations led to BPA serum concentrations similar to those described in human biomonitoring studies.

Este trabalho teve como objetivo investigar os efeitos da exposição pré-natal a duas doses de etanol sobre o desenvolvimento e a atenção de ratos. Método: 49 ratas Wistar prenhes distribuídas em quatro grupos de acordo com o tratamento gestacional: A35 – dieta líquida com 35% de calorias derivadas do etanol (CDE): A10 – dieta líquida com 10% CDE; Controle – dieta líquida sem etanol; Chow – livre acesso à água e ração. No estudo I, foram avaliados o peso, os reflexos (geotaxia negativa e força de agarrar) e a atividade locomotora dos filhotes. No grupo A35, apenas 43% dos filhotes sobreviveram. Os animais desse grupo apresentaram menor peso que os demais, prejuízos na tarefa de força de agarrar e maior atividade locomotora. No estudo II, 12 filhotes machos adultos de cada grupo foram testados na Tarefa serial de cinco escolhas. Os animais do grupo A35 apresentaram maior número de omissões, principalmente no final das sessões. Conclusão: Efeitos do etanol são dose-dependentes e podem estar associados com um prejuízo atencional específico. / The objective of this study was to investigate the effects of prenatal exposure to two doses of ethanol on developmental milestones and attention of rats. Method: 49 pregnant Wistar rats were assigned to one of four gestational treatments: A35 - liquid diet with 35% ethanol-derived calories (EDC); A10 - liquid diet with 10% EDC; Control – ethanol-free liquid diet; Chow – laboratory chow and water. In study I, litters were tested for body weight, negative geotaxis, grip strength and locomotor activity. Only 43% of A35 pups survived. A35 weighed less than other groups, performed worse in grip strength and presented more locomotor activity. In study II, 12 male twomonth old rats from each group were tested in the Five choice serial reaction time task. A35 performed more omission errors than other groups, mainly during the final part of the sessions. Conclusion: Ethanol effects are dose-dependent and might be associated with a specific attentional deficit.