Plasma lipoproteins and preeclampsia in women with type 1 diabetes: a prospective study.

CONTEXT: In nondiabetic pregnancy, cross-sectional studies have shown associations between maternal dyslipidemia and preeclampsia (PE). In type 1 diabetes mellitus (T1DM), the prevalence of PE is increased 4-fold, but prospective associations with plasma lipoproteins are unknown. OBJECTIVES: The aim of this study was to define lipoprotein-related markers and potential mechanisms for PE in T1DM. DESIGN AND SETTINGS: We conducted a multicenter prospective study in T1DM pregnancy. PATIENTS: We studied 118 T1DM women (26 developed PE, 92 remained normotensive). Subjects were studied at three visits before PE onset [12.2 ± 1.9, 21.6 ± 1.5, and 31.5 ± 1.7 wk gestation (means ± SD)] and at term (37.6 ± 2.0 wk). Nondiabetic normotensive pregnant women (n = 21) were included for reference. MAIN OUTCOME MEASURES: Conventional lipid profiles, lipoprotein subclasses [defined by size (nuclear magnetic resonance) and by apolipoprotein content], serum apolipoproteins (ApoAI, ApoB, and ApoCIII), and lipolysis (ApoCIII ratio) were measured in T1DM women with and without subsequent PE. RESULTS: In women with vs. without subsequent PE, at the first and/or second study visits: low-density lipoprotein (LDL)-cholesterol, particle concentrations of total LDL and large (but not small) LDL, serum ApoB, and ApoB:ApoAI ratio were all increased (P < 0.05); peripheral lipoprotein lipolysis was decreased (P < 0.01). These early differences remained significant in covariate analysis (glycated hemoglobin, actual prandial status, gravidity, body mass index, and diabetes duration) but were not present at the third study visit. High-density lipoprotein and very low-density lipoprotein subclasses did not differ between groups before PE onset. CONCLUSIONS: Early in pregnancy, increased cholesterol-rich lipoproteins and an index suggesting decreased peripheral lipolysis were associated with subsequent PE in T1DM women. Background maternal lipoprotein characteristics, perhaps masked by effects of late pregnancy, may influence PE risk.

Maternal folate and cobalamin status predicts vitamin status in newborns and 6-month-old infants.

Our aim in this longitudinal study was to determine predictors of folate and cobalamin status in infancy. Data were collected from 364 mother-infant pairs with blood measurements from pregnancy ( approximately 18 wk; n = 149), newborns (cord serum; n = 361), and 6-mo-old partially or exclusively breast-fed children (n = 221). Serum/plasma folate, cobalamin, holotranscobalamin (holoTC), holohaptocorrin (holoHC), methylmalonic acid (MMA) and total homocysteine (tHcy) at birth and 6 mo were related to maternal vitamin status, parity, lifestyle variables, and anthropometry. In multivariate analyses, the strongest predictors of folate at birth and 6 mo were maternal folate and cord folate, respectively (P < 0.01). Maternal holoTC best predicted cobalamin status at birth (positively associated with cord cobalamin, holoTC, and holoHC; inversely with MMA and tHcy; P < or = 0.001), whereas maternal and cord holoHC were the strongest predictors of cobalamin status at 6 mo (positively associated with cobalamin, holoTC, holoHC; inversely with tHcy; P < 0.05). The association between cobalamin status and parity was negative at birth but positive at 6 mo. Birth weight, female sex, and smoking were associated with low cobalamin or high tHcy at birth but showed no or opposite associations at 6 mo. In conclusion, maternal folate and cobalamin status exerts a long-term positive effect on infant vitamin status. The effect of smoking, parity and female sex on cobalamin status did not persist beyond the newborn period. Maternal holoTC was the superior predictor of newborn cobalamin status, while holoHC could be a valuable marker for predicting cobalamin status later in infancy.

Pregnancy complications by overweight and residential area. A prospective study of an urban Norwegian cohort.

BACKGROUND: Health varies in residential areas of different socioeconomic status in the capital of Norway. This study compares risks of pregnancy complications in Oslo according to prevalence of overweight and areas of residency. METHODS: Prospective cohort study of 3,677 pregnancies. Pregnancy outcomes were retrieved from medical records after delivery. Statistics were performed by logistic regression analyses. RESULTS: Pregnant women from areas of lower socioeconomic status (Oslo East) had higher prevalence of overweight than women from areas of higher status (Oslo West). Dose-response relationships were found between body mass index and increased risk of pregnancy complications (pre-eclampsia, gestational hypertension, gestational diabetes mellitus, macrosomia, cesarean deliveries, acute cesarean deliveries, transfer of the newborn to neonatal intensive care unit). Comparing Oslo East with Oslo West the relative risks of pregnancy complications were 1.8 for pre-eclampsia, 1.6 for gestational diabetes, 1.4 for acute cesarean deliveries, 1.6 for low birth weight (< or =2,500 g) and 1.5 for transfer to neonatal intensive care. Adjustment for body mass index did not change the increased risks of pre-eclampsia, acute cesarean deliveries, low birth weight, or transfer to neonatal intensive care among Oslo East women. Only the increased risk of gestational diabetes could partially be explained by higher body mass index. CONCLUSIONS: Residential areas of lower socioeconomic status had higher risk of pregnancy complications. Overweight was a strong independent predictor of pregnancy complications. The higher prevalence of overweight in Oslo East could, however, not explain the increased risk of pregnancy complications.

[Fetal nutrition and future health]. / Ernaering i fosterlivet og fremtidig helse.

Fetal nutrition may permanently affect physiological properties of the new individual and hence the risk of future disease. Epidemiological studies indicate that fetal nutrition may significantly influence the risk of diabetes, cardiovascular disease, and cancer. Controlled animal studies show that even properties traditionally considered as exclusively genetic, like fur colour, may be modified by altered maternal nutrition. The expression "fetal programming" has been introduced to describe permanent effects of environmental conditions in fetal life. An important mechanism of fetal programming seems to be epigenetic regulation. One example of epigenetic regulation is methylation of the DNA base cytosine in promoter regions of some genes. DNA methylation will lead to decreased gene expression. Over the last two decades, marked changes in dietary habits and other life style features have taken place among young Norwegian women. This is particularly reflected in the increasing prevalence of obesity. Maternal weight and metabolic status is closely associated with the growth and development of the fetus. Thus, diet and physical activity become particularly important aspects of the health of young women.

Absence of enhanced systemic inflammatory response at 18 weeks of gestation in women with subsequent pre-eclampsia.

OBJECTIVE: To compare indicators of systemic inflammatory response in the second trimester in women who developed pre-eclampsia with normal pregnancies. DESIGN: Prospective nested case control study derived from a cohort of 2190 pregnant women. Blood samples were obtained at 18 weeks of gestation. The following inflammatory parameters were measured: tumour necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor-1 (PAI-1), interleukin-1beta (IL-1beta), IL-6, IL-10, microCRP and tissue factor (TF). SETTING: Institute of Medical Genetics, University of Oslo, and Department of Medical Genetics, Ullevål University Hospital and Departments of Obstetrics and Gynecology, Aker University Hospital, Oslo, Norway. SAMPLE: The cases were 71 women who subsequently developed pre-eclampsia. The controls were 71 healthy, pregnant women matched for age, parity and first trimester body mass index (BMI). METHODS: Venous blood was drawn from fasting subjects into 5 mL test tubes containing EDTA. Samples were analysed for inflammatory parameters: IL-1-beta, IL-6, IL-10, TNF-alpha, PAI-1, TF (ELISA-technique) and CRP (latex-enhanced immunonephelometric assay), strictly according to the manufacturer's recommendation. MAIN OUTCOME MEASURES: The matched case and control subjects were compared by the paired two-tailed Wilcoxon signed rank test. All P values were two-tailed and P < 0.05 was deemed statistically significant. RESULTS: We found no differences in plasma concentrations of PAI-1, IL-1beta, IL-6,IL-10, microCRP, TNF-alpha or TF at 18 weeks of gestation between women who subsequently developed pre-eclampsia and matched control women. CONCLUSION: In contrast to findings from women with overt pre-eclampsia, the present study indicates that there are no indications of intensified systemic inflammatory response at 18 weeks of gestation in women who later develop pre-eclampsia.

The fetal origins hypothesis: placental insufficiency and inheritance versus maternal malnutrition in well-nourished populations.

The 'Fetal origins hypothesis' states that individuals born small because of malnutrition are predisposed to adult diseases. Fetal malnutrition has two main causes, poor maternal nutrition and placental insufficiency. A distinction between these causes is important because it is likely that maternal nutrition has been sufficient in the majority of populations in which the fetal origins hypothesis has been tested. Thus, placental insufficiency is a more reasonable cause of reduced fetal growth in adequately nourished populations. Placental insufficiency is mainly due to inadequate vascular adaptation at the uteroplacental interface ('poor placentation'). Among women with placental insufficiency syndromes such as pre-eclampsia and 'idiopathic' intrauterine growth retardation, there is an increased prevalence of risk factors for cardiovascular diseases. Maternal cardiovascular risk factors may therefore increase the risk of adult diseases in the offspring both through direct inheritance and by interfering with uteroplacental vascular adaptation. The latter may result in placental insufficiency and fetal growth retardation that by itself could cause adult disease (as the Fetal origins hypothesis states). Alternatively, the association between low birth weight for gestational and adult disease could be an epiphenomenon, leaving inheritance as the main explanation for the fetal origins hypothesis, in adequately nourished populations.