Our objectives were to measure concentrations of glucose, insulin, insulin-like-growth-factor-binding-protein-1 (IGF BP1) and beta-hydroxybutyrate (BOHB) in amniotic fluid (AF), and establish if these concentrations were associated with emergence of maternal gestational diabetes mellitus (GDM). AF samples (n=408) were collected following routine amniocentesis (12-22 weeks gestation). Glucose and insulin concentrations were elevated in our GDM mother-infant pairs, where GDM was associated with a 176g increase in birth weight. Logistic regression showed that AF glucose but not insulin was associated with developing GDM. Non-linear Bayesian probability plots showed that when 2nd trimester glucose was plotted against insulin increases in both were predictive of the subsequent emergence of GDM. In conclusion, our findings show that: (1) AF glucose but not insulin predicts subsequent emergence of GDM and (2) these observed elevations provide evidence that the fetus of GDM mothers is being exposed early in-utero to metabolic perturbations (i.e. elevated glucose) that may have important long-term metabolic consequences for their future development.

The mechanisms which control the accumulation and circulation of the amniotic fluid are poorly understood. Earlier studies had made the tentative suggestion that vasopressin, which is important in the control of water balance in adults, might play a role in the regulation of amniotic fluid turnover. In the work reported here, attempts were made to detect and measure the vasopressin levels in the amniotic fluid of guinea pigs, sheep and humans. Unconcentrated amniotic fluid samples from the guinea pig, sheep and human were assayed using the water-loaded, alcohol-anesthetized rat antidiuretic preparation. If vasopressin is present in the fluid of these animals, it would be at a concentration below the detectable limits of the assay, which were found to be 10 to 15 microunits/ml. Only 4 out of 36 experiments on guinea pig amniotic fluid gave even a suggestion of a response, with 3 of these being too small to be quantified accurately. No sheep or human samples produced an antidiuresis. An attempt was made to dehydrate the maternal guinea pigs, as it. was thought that this would create an osmotic stress in the fetus which might result in increased output of vasopressin. In 29 experiments with fluid of fetuses whose mothers had been without water for 24 or 48 hours prior to collection, 27 gave no response. The responses to the two injections that did indicate activity were too low for accurate quantification. However, these experiments were not considered conclusive, and more extended investigation is needed. Seven human amniotic fluid samples were concentrated on CM-25 Sephadex columns, along with three standard vasopressin loads. The standards showed recoveries of 80% to 90% under optimal conditions. An antidiuretic substance was found in fractions from all of these samples, and it eluted at a similar pH and molarity to the standard vasopressin. This material measured approximately 200 micro-units/ml, and was relatively consistent in all of the samples tested. The amniotic fluid antidiuretic substance (AFAS) appeared to respond with an antidiuresis similar to that of vasopressin on the assay preparation. However, further work suggested that the AFAS could not be identified as vasopressin. Although the pattern of antidiuretic responses were similar, there were marked changes in the sensitivity of the bioassay preparation to the unknown material during periods of little change in the responses to vasopressin itself. A similar contrast was found between different experiments. Sodium thioglycollate incubation also failed to deactivate the active AFAS fractions, whilst control volumes of vasopressin lost apparently all activity following this procedure. The stability characteristics were also dissimilar to those of vasopressin, as the fractions remained active for up to five weeks when stored at neutral pH at 4° C. Optimum pH conditions for the storage of vasopressin are between 3.0 and 5.0. An attempt was made to identify the AFAS as angiotensin II. However, the response pattern on the records of the antidiuretic assay were dissimilar. Further comparisons with combinations of vasopressin and angiotensin II in varying concentrations also failed to mimic the responses to the AFAS. It was concluded that the antidiuretic activity found in the human amniotic fluid was not attributable to vasopressin, angiotensin II, or to a combination of these two hormones, at the levels tested. The nature of the AFAS is at present unknown. Further studies are needed to identify the unknown antidiuretic agent extracted from human amniotic fluid, and the possible mechanisms of its release, and its potential physiological functions, are still unknown. / Science, Faculty of / Zoology, Department of / Graduate

No description available.

Amniotic fluid (AF) is a protective pool and a resource of amino acids for the growing fetus. In study 1, we investigated if any of these AF amino acids at mid gestation were associated with fetal development in humans. Nineteen amino acids differed across birth weight percentiles. Arginine, 3-methyl histidine and tryptophan were positive predictors of birth weight, while ornithine was a negative predictor. In study 2, we used a diet induced model of IUGR to see if specific AF amino acids were predictive of fetal weight near term. Methionine and phenylalanine were modified by diet, and 12 amino acids were independently modified by gestational age, respectively. Cysteine, lysine, methionine and tyrosine were predictors of fetal weight. Thus, the AF amino acid pool is associated in animals and humans with fetal growth.

Using second trimester amniotic fluid (AF), the objectives of this study were two-fold: 1) to investigate the relationship between AF glucose and insulin levels as a predictor of macrosomia and 2) to create a risk profile for macrosomia (LGA> 90th percentile) using a combination of AF glucose and insulin concentrations. Amniotic fluid samples were obtained from non-diabetic women (n = 542) undergoing age-related amniocentesis (12th to 22nd week). AF glucose was quantified using a standard hexokinase assay and AF insulin was quantified using the Beckman Access ultrasensitive assay system. Although LGA infants were found to have significantly higher concentrations of insulin and glucose in their 2nd trimester AF, logistic regressions showed that neither alone predicted the outcome of macrosomia. However, a Bayesian two-dimensional contour map plotted the risk for LGA using both AF glucose and insulin. The two-dimensional contour map illustrated the value in considering AF glucose and insulin together to predict LGA in newborns.

To investigate the relation between amniotic fluid (amf) constituents and human fetal growth and birth weight (b.wt), amf was collected from 395 pregnant women undergoing routine amniocentesis at 14--16 weeks' gestation at the Royal Victoria (RVH), Jewish General (JGH), and St. Mary's (SMH) Hospitals. The fluid was analyzed for total protein, albumin, urea nitrogen, creatinine, uric acid, glucose, beta-hydroxybutyrate (betaHBA), and lactate. Maternal and neonatal data were collected from a questionnaire at the time of recruitment and from medical charts post-delivery. The mean b.wt in our population was 3409 +/- 552g. Birth weight differed significantly by infant gender, maternal height (ht), and prepregnancy weight (wt), as determined by one-way analysis of variance (ANOVA). Of the amf constituents measured, glucose showed strong evidence of being a potential predictor of b.wt, such that for each mmol/L increase in amf glucose a 119.4g increase in b.wt was observed. Lactate showed a similar but weaker tendency toward predictive value. Ongoing research is currently being done to further examine the role of human amf constituents in predicting b.wt, the goal being to develop a predictive model that would aid in preparing for and preventing aberrations in fetal growth.

The objectives of the study were to measure the concentrations of albumin, transferrin, IgG and uric acid in 2nd trimester amniotic fluid (AF) and to establish if these concentrations were associated with infant birth outcomes. / Amniotic fluid samples (n=230) were collected from mothers undergoing routine amniocentesis (12-20 wk). Maternal characteristics like height, pre-pregnancy weight, age, smoking status, parity and infant gender, birth weight and gestational age were collected from questionnaires and obstetrical medical chart review. AF samples were analyzed by capillary zone electrophoresis (CZE). / The results showed that the 2nd trimester AF uric acid was a significant predictor of infant birth weight (grams) and transferrin was negatively associated with gestational age in term infants.

Thesis (M.Sc.). / Written for the School of Dietetics and Human Nutrition. Title from title page of PDF (viewed 2007/08/30). Includes bibliographical references.

Thèse--Liège. / Includes bibliography.

Thèse--Liège. / Includes bibliography.