OBJETIVOS: La diabetes gestacional (DG) es una entidad que se ha relacionado con un mayor riesgo de complicaciones gestacionales. Los objetivos de este estudio fueron: 1) determinar el impacto de la hiperglucemia leve, 2) evaluar las asociaciones entre las complicaciones gestacionales y el grado de tolerancia a la glucosa, obesidad maternal pregestacional, 3) conocer cuál es el rol del sexo fetal en el desarrollo del propio feto en relación a la presencia de DG y obesidad materna pregestacional, y 4)conocer la prevalencia de la DG según los diferentes criterios diagnósticos (criterios de la National Diabetes Data Group y de la Asociación Americana de Diabetes). MÉTODOS: Estudio poblacional prospectivo multicéntrico, que incluyó 9.270 mujeres gestantes con feto único y sin diabetes pregestacional conocida que dio lugar a 4.793 recién nacidos de sexo masculino y 4.477 de sexo femenino. Las mujeres fueron categorizadas según el grado de tolerancia a la glucosa y según IMC pregestacional. Se evaluó el riesgo de macrosomía, tasa de cesáreas y de otras 7 complicaciones gestacionales, mediante modelos de regresión logística múltiple y se calculó el riesgo atribuible en la población. RESULTADOS-CONCLUSIONES: 1) Las mujeres con hiperglucemia leve presentaron una asociación con la presencia de complicaciones similar al grupo control, por lo que no se aconseja un cambio en los criterios diagnósticos. 2) En términos de riesgo absoluto y en términos de freceuncia del riesgo atribuible en la población la contribución de la hiperglucemia leve en las complicaciones gestacionales fue inferior a la presentada por la obesidad materna. 3) Se demostró un dimorfismo sexual en la frecuencia de las complicaciones gestacionales. La presencia de DG sólo se relacionó con morbilidad fetal exclusivamente en el sexo masculino. 4) La prevalencia de DG fue del 8,8% con los criterios NDDG y del 11,6% con los criterios de Carpenter y Coustan (incremento relativo del 31.8%). / OBJECTIVE: Gestational diabetes mellitus (GDM) increases the risk of adverse complications for both mother and child during pregnancy. The objectives of this study were: 1) To evaluate the potential impact of mild hyperglycemia on GDM outcomes; 2) To evaluate the associations among adverse gestational outcomes and glucose tolerance status and maternal obesity; 3) To elucidate whether the adverse gestational outcomes is influenced by maternal obesity and abnormal glucose tolerance differently in male and female fetuses. 4) To know GDM prevalence according to the different diagnostic criteria (National Diabetes Data Group and American Diabetes Association criteria). Methods: A population study in 16 general hospitals from the Spanish National Health Service -that included 9,270 consecutive women with singleton pregnancies and without a former diagnosis of diabetes mellitus delivering 4,793 male and 4,477 female newborns- was conducted. Women were categorized according to glucose tolerance status and pregestational body mass index (BMI). Fetal macrosomia, caesarean section and seven secondary outcomes were evaluated. Logistic regression analyses were performed to predict the effect of maternal BMI category and glucose tolerance on gestational outcomes. The population-attributable fractions (PAf) of predictor variables were also calculated. RESULTS/CONCLUSIONS: 1) The contribution of mild hyperglycemia to adverse GDM outcomes was not significantly different to that of control group. Therefore a change in diagnostic criteria was not warranted in our setting. 2) Pregestational maternal BMI (both the absolute risk and PAf) exhibited a much stronger influence on macrosomia, Caesarean section, pregnancy-induced hypertension and large-for-gestational-age newborns than glucose tolerance status. 3) There was a sexual dimorphism in the risk of abnormal birth weight attributed to maternal glucose tolerance status. A closer surveillance of fetal growth might be warranted in pregnant women with abnormal glucose tolerance carrying a male fetus. 4) Of 9,270 pregnant women screened for GDM, 819 (8.8%) met National Diabetes Data Group criteria. If the threshold for defining GDM had been lowered to ADA criteria, an additional 2.8% of women would have been defined as having the condition (relative increase of 31.8%).

Alcohol abuse during pregnancy has been associated with Fetal Alcohol Spectrum Disorder (FASD). Research to date has focused on the role played by ethanol in the development of this disorder. In addition to ethanol, alcoholic drinks also contain methanol. Hence, consumption of alcohol can also lead to methanol accumulation. Methanol is metabolized to formaldehyde, which is then rapidly metabolized to formate, a toxic metabolite. Folate, a B-vitamin and antoxidant, is a cofactor in the metabolism of formate. This study assessed the relationship between formate and folate, formate kinetics in folate deficiency and, changes in antioxidant capacity during formate insult in folate deficiency. The findings of this study would lead to a better understanding of the role of formate in the development of the etiology of FASD and form the basis of future research. The relationship between formate and folate was investigated in intoxicated human female subjects, sober drug rehabilitating females and, pregnant women. A negative (inverse) relationship was observed between plasma formate and folate in pregnant sober women (correlation coefficient = -0.4989). Such a relationship, however, was not observed in whole blood in alcohol intoxicated (correlation coefficient = 0.0899) and detox women (correlation coefficient = 0.2382). Because of the health promoting ingredients in grain and fruit based alcoholic drinks, antioxidant B-vitamins were higher during intoxication while homocysteine levels were lower.<p>Formate kinetics during folate deficiency and changes in the body antioxidant capacity was investigated in folate deficient young swine. Folate deficiency altered formate kinetics leading to decreased systemic clearance (by approximately 2.3 fold), increased half-life (by 2.5 fold) and, consequently increased exposure (by 2.7 fold). Folate deficiency alone compromised antioxidant capacity. However, the combination of folate deficiency and formate insult further compromised antioxidant capacity.<p>In conclusion, methanol accumulates after alcohol intoxication, which can lead to formate build up in the body. During folate deficiency formate kinetics is altered leading to reduced formate clearance and increased exposure. Exposure to formate coupled to folate deficiency compromises antioxidant capacity, which can have deleterious effects on the fetus.

The purpose of this study was to come to a greater understanding of the experiences of birth mothers of children with FASD since the birth of their child. The principles of feminist research practice were utilized throughout in order to give a voice to the women who participated in the study. The research followed the general guidelines to conducting hermeneutic phenomenology outlined by van Manen (1990). Purposeful sampling was used to recruit four birth mothers of children with FASD who have been involved in the mothering of that child. Data was generated through three semi-structured interviews with each participant, including a hermeneutic interview in which the women participated in the process of interpretation. Data was analysed using selective, detailed and wholistic methods and through the process of writing and re-writing (van Manen, 1990).<p> The results focus on the social and emotional experiences of the women who participated in the study. The experience of being a birth mother of a child with FASD is represented in a discussion of four main themes: Living with the Past: Self-Forgiven, yet Always Present; Living with Others: Judgement and Understanding; Living with the Self: Unworthy and Unfit; and Living with Ambivalence: Mothering as a Birth Mother. The implications of this research in relation to the understanding of the experiences of birth mothers of children with FASD and potential supports are discussed.

Environmental stress during embryonic development could lead to growth restriction of the embryo, and act as a risk factor for the development of cardiovascular disease in adult life. A common environmental stressor that causes growth restriction is prenatal hypoxia, which has been shown to adversely affect adult health in mammalian models. Prenatal hypoxia causes an increase in catecholamines which results in over stimulation of the cardiac β-adrenergic receptors. Previous work on chickens has shown that prenatal hypoxia causes an increase in the sensitivity of β-adrenergic receptors to epinephrine in the embryonic heart. The sensitivity of these receptors was found to be decreased in prenatal hypoxic juvenile. Prenatal hypoxia has no significant effect on the density of these receptors in neither the embryo nor the juvenile. The lack of change in receptor density implies that the effects of hypoxia are further down stream in the signalling cascade. The β2 adrenergic receptor can couple to both the stimulatory Gα subunit (Gsα) and the inhibitory Gα subunit (Giα). We hypothesized that prenatal hypoxia would cause an increase in the Gsα in the sensitized embryos, while increasing Giα in the desensitized juveniles. This study evaluated the relative levels of Gsα and Giα in the hypoxic chicken embryo, and in the prenatally hypoxic juvenile, Using western blotting. Hypoxia considerably increased Giα in the chicken embryo while having no effect on Gsα. In the prenatally hypoxic juvenile Gsα was significantly increased while no changes were found in Giα. This dissociation between the levels of Gα subunit and receptor sensitivity implies that that hypoxia affects the signaling cascade downstream of the Gα subunit.

<p>Enligt Statistiska Centralbyrån [SCB] föddes det år 2008 109 301 barn i Sverige. Utöver dessa föddes det cirka 600 barn som dött i livmodern innan förlossning. Intrauterin fosterdöd innebär att barn föds döda efter graviditetsvecka 22. Tidigare forskning belyser vikten av att barnmorskor har ett individuellt synsätt vid mötet med par vid intrauterin fosterdöd. Forskningen åskådliggör även hur föräldrar upplevt det stöd som givits under förlossningen. Det finns dock relativt lite forskning kring hur barnmorskor stödjer vid intrauterin fosterdöd. Syftet med detta arbete var därför att undersöka hur barnmorskor upplever sitt stöd i samband med förlossning vid intrauterin fosterdöd. Metoden som användes var kvalitativ innehållsanalys med en induktiv ansats. Fem barnmorskor intervjuades på två förlossningsavdelningar i Västra Götaland och Örebro län. I analysprocessen framkom tre huvudkategorier;<em>individanpassa, ge tid</em> och <em>vara ett verktyg.</em> Resultatet visar att barnmorskors stöd under förlossning inriktar sig på att låta paren styra informationsflödet och genom närvaro lyssna in behoven. Det var av vikt att ge paren tid i förlossningsarbetet men även tid i mötet med barnet. För att stödja bör barnmorskan känna sig trygg både i sig själv och i sin profession. En trygghet kring sin egen syn på döden var också av betydelse i stödet.</p> / <p>According to the Swedish bureau of Statistics [SCB] there were 109 301 children born in Sweden during 2008, in addition to these there where also approximately 600 stillborn children. Intrauterine fetal death means that the child has died in the womb after the 22nd week of pregnancy. Previous research highlights the importance of the midwives´ individual approach to parents with a stillborn child. Research also illustrates how parents experienced the support given during delivery. However, there is a limited amount of research done on how midwives support the parents of a stillborn child. The aim of this study was there for to investigate how midwives experience there support during delivery of a stillborn child. The method used was qualitative content analysis with an inductive approach. Five midwives were interviewed at two maternity wards in Västra Götaland and Örebro County. The analysis process revealed three main categories; <em>adjust to the individual, to give time</em> and <em>to be a tool.</em> The result shows that midwife´s support during delivery focuses on allowing couples to control the flow of information and by being present judge the parents´ needs. It is important to give the parents time both during delivery and to spend time with the stillborn child. To be able to support, the midwife need to feel confident both personally and professionally. It was also significant what the midwife´s own view on death was.</p>

The purpose of this study was to look at the genotoxic and cytotoxic effects of benzo-á-pyrene (BáP), a chemical mutagen that is present in cigarette smoke, on the insulin-like growth factor-I (IGF-I) gene. Women who smoke during pregnancy are more likely to have a growth-restricted baby. We hypothesized that BáP exerts its effects through genotoxic and cytotoxic avenues. The cytotoxicity is manifested by chromosomal abnormalities and a decrease in the rate of cell division. The genotoxicity is manifested by changes in certain genes known to be important in mammalian fetal development such as IGF-I. IGF-I is implicated in intrauterine growth restriction (IUGR), a problem that greatly increases the risk of perinatal morbidity and mortality. To futher understand the mechanism by which BáP influences the normal growth and development of human placental cells, human placental trophoblast cells from an established immortalized cell line were utilized. Cells were cultured in appropriate media, starved (using starvation "Serum Free Medium"), and treated with two doses of BáP, 1µM (dose 1) and 5µM (dose 2). Chromosomes were prepared for cytogenetic analysis and visualized using light microscopy after Giemsa staining. Chromosomal aberrations were identified and the rate of cell division was determined through the analysis of the mitotic index for treated cells compared to a control group. To further understand the influence of BáP on the IGF-I gene expression level, RNA was extracted from control and treated cells, from which cDNA was synthesized and used for further analysis using polymerized chain reaction (PCR). The PCR results were used to better understand the genotoxicity of BáP, while chromosomal aberration analysis was used to determine the cytotoxic effects of BáP on human placental cells. Our results indicate that many chromosomal abnormalities were present in the treated groups compared to the control group. In addition, there was a significant decrease in the mitotic index of the BáP-treated cells (MI=0.3%) verses the control group (MI=0.93%), p value 0.0447. Through the PCR assay, we speculate that there is a dose-related response to BáP of the IGF-I RNA expression level, with low levels in the treated groups compared to the control group. We conclude from these results that BáP influences placental cells at both the gene and chromosome level. It also affects the cell cycle of human placental cells. It is known that smoking is deleterious for fetal development. We believe that the current study brings us closer to understanding the mechanism by which smoking can lead to fetal growth restriction.

Placental vessels and the umbilical circulatory network function to carry oxygen and nutrients to the fetus. It is at this level that placental lesions such as villitis, obliterative vasculopathy, and thrombotic vasculopathy have been observed in association with fetal inflammatory response syndrome (FIRS) and cerebral palsy. We used human umbilical vein endothelial cells (HUVECs) as a model to study the regulation of inflammation and thrombosis in fetal vessels by microbial products. In this thesis we measured interleukin-8 (IL-8) and tissue factor (TF) expression by HUVECs treated with lipopolysaccharide (LPS), poly (I:C) (PIC), and peptidoglycan (PG). Our results show a profound induction of IL-8 by PIC, a TLR-3 ligand. We also show a moderate induction of tissue factor expression in PIC-treated HUVECs. These results show that HUVECs are exquisitely sensitive to PIC and suggests an important role for viral infection in umbilical vessel inflammation. We additionally treated HUVECs with dexamethasone (DEX), an anti-inflammatory steroid, and melatonin (MT), a pineal gland product with immunomodulatory and anti-oxidant properties. DEX reduced the level of both IL-8 and TF expression in PIC-treated cells. MT, however, further enhanced IL-8 expression in PIC-treated cells. Our results indicate a potential role for glucocorticoid therapy in reducing placental vessel inflammation and thrombosis. Thus, intervention with GC in pregnancies with FIRS may reduce the severity of placental lesions associated with cerebral palsy.

This retrospective case-control study was designed to investigate the relationship between placental localization and intrauterine growth restriction (IUGR). Pregnant women with an anatomic survey from January 1, 2000, to December 31, 2005, and delivery of the pregnancy at Yale-New Haven Hospital (YNHH) were identified using clinical and billing records. Multiple gestation, fetal anomaly, and incomplete medical information were reasons for exclusion. Cases (N=69) were consecutive pregnancies with evidence of IUGR (estimated fetal weight <10th percentile for gestational age) at last follow-up ultrasound. Randomly selected controls (N=258) from the same time period had no evidence of IUGR. Maternal, ultrasound, delivery, and perinatal data were collected by retrospective medical record review, and IUGR cases and non-IUGR controls were compared using the Students t-test, Wilcoxon test, Chi-square analysis, Fishers exact test, and ANOVA. Placental location was determined from the anatomic survey record (obtained at 18.4 ± 1.2 weeks gestation in the IUGR group and 18.2 ± 1.0 weeks gestation in the control group; P=0.18). Multivariate logistic regression with adjustment for confounders was used to investigate the association between IUGR and placental localization. Consistent with known predictors of IUGR, the IUGR group had a higher proportion of black women (36.4% vs. 19.8%, P=0.03), chronic hypertension (26.0% vs. 3.5%, P<0.001), and hypertensive disorders of pregnancy (36.2% vs. 5.0%, P<0.001). Mean birth weights of IUGR and non-IUGR pregnancies differed by 2 kilograms (3244 ± 625 grams vs. 1277 ± 637 grams, P<0.001). IUGR infants were more likely to receive antenatal steroids, deliver preterm, deliver by cesarean section, and be admitted to neonatal intensive care. In both IUGR and non-IUGR pregnancies, the placenta was most commonly anterior or posterior. Unilateral placentas were three times more common in the IUGR group than in the non-IUGR group (17.4% vs. 5.0%, P=0.01). IUGR pregnancies were over four times as likely as control subjects to have unilaterally-located placentas compared to anterior placentas (OR 4.8, 95% confidence interval, 1.9-11.7). Adjusting for ethnicity, chronic hypertension, and hypertensive disorders of pregnancy did not affect this finding (OR 4.6, 95% confidence interval 1.6-13.5). In conclusion, we compared a group of 69 IUGR pregnancies to 258 non-IUGR controls and found intrauterine growth restriction to be associated with unilateral placentation.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2002. / Vita. Includes bibliographical references (leaves 94-106).