Emanuela Taricco

Fetal Plasma Leptin Concentrations: Relationship with Different Intrauterine Growth Patterns from 19 Weeks to Term

The relationship between in utero fetal growth and fetal leptin concentrations was investigated between 19 and 41 wk in 40 normal (appropriate for gestational age, AGA) fetuses, in 25 intrauterine growth-restricted (IUGR) fetuses, and in 18 fetuses from gestational diabetic mothers (GDM), representing different intrauterine growth patterns. Umbilical venous plasma leptin concentrations were determined at the time of either in utero fetal blood sampling or delivery. Plasma leptin was measurable as early as 19 wk of gestation. A significant difference was observed between umbilical venous and arterial plasma leptin concentrations (0.6 ± 0.6 ng/mL;p < 0.01). In AGA and in IUGR fetuses, significant positive relationships were found between fetal leptin concentrations and both gestational age (p < 0.001) and fetal weight (p < 0.001). Leptin concentrations were significantly higher in AGA than IUGR only after 34 wk (p < 0.05), but leptin per kilogram fetal weight (leptin/kg) was not significantly different. In IUGR with abnormal umbilical arterial Doppler velocimetry and fetal heart rate, leptin/kg significantly higher than in IUGR with normal biophysical and biochemical parameters was found (p < 0.05). Both circulating plasma leptin and leptin/kg were significantly higher in GDM than in normal fetuses (p < 0.001) and correlated with abdominal fat mass measured by ultrasound. No gender differences were observed in any group of fetuses. These findings indicate a clear relationship between fetal leptin concentrations and fetal fat mass. Data in severe IUGR suggest the presence of increased leptin concentrations associated with in utero signs of fetal distress.

Effects of gestational diabetes on fetal oxygen and glucose levels in vivo

Objective  Fetal hypoxia and acidemia have been reported in pregestational diabetic pregnancies in relation to poor glycaemic control, but it is still uncertain whether this is the case in apparently well‐controlled gestational diabetes.

Flexible treatment of gestational diabetes modulated on ultrasound evaluation of intrauterine growth: a controlled randomized clinical trial.

OBJECTIVES In order to prevent abnormalities of fetal growth still characterizing pregnancies complicated by Gestational Diabetes (GDM), in the present study we evaluated a therapeutic strategy for GDM based on ultrasound (US) measurement of fetal insulin-sensitive tissues. METHODS All GDM women diagnosed before 28th week immediately started diet and self-monitoring of blood glucose; after 2 weeks they were randomized to conventional (C) or modified (M) management. In C the glycemic target (GT) was fixed at 90 fasting/120 post-prandial mg/dl; in M GT varied, according to US measurement of the Abdominal Circumference (AC) centile performed every 2 weeks: 80/100 if AC > or =75th, 100/140 if AC<75th. Therapy was tailored to mean fasting (FG) and postprandial glycemia (PPG). RESULTS Globally, 229 women completed the study, 78 in C, 151 in M. Use of insulin was 16.7% in C, 30.4% in M (total groups), significantly more frequent in M than in C (59.7% vs 15.4%) when considering only women with AC > or =75th c. Mean metabolic data were similar in the 2 groups, but in M a tightly-optimized subgroup, resulting from the lowering of GT due to AC > or =75th, coexisted with a less-controlled one, whose higher GT was justified by AC<75th. Pregnancy outcome was better in M, with lower (p<0.05*) rate of LGA* (7.9% vs 17.9%), SGA (6.0% vs 9.0%) and Macrosomia* (3.3% vs 11.5%). CONCLUSIONS Our data show the value of a flexible US-based approach to the treatment of GDM. This model does not necessarily involve a generalized aggressive treatment, allowing to concentrate therapeutical efforts on a small subgroup of women showing indirect US evidence of fetal hyperinsulinization. Such a selective approach allowed to obtain a near-normalization of fetal growth, with clear advantages on global pregnancy outcome.

Gestational Diabetes Mellitus Upsets the Proportion of Fatty Acids in Umbilical Arterial but Not Venous Plasma

OBJECTIVE—Neonates of women with gestational diabetes mellitus (GDM) have reduced levels of arachidonic acid (AA) (20:4 n-6) and docosahexaenoic acid (DHA) (22:6 n-3). To assess whether this is the result of impaired placental transfer or endogenous fetal metabolism, fatty acids in umbilical venous and arterial plasma were analyzed in neonates of GDM women. RESEARCH DESIGN AND METHODS—Fatty acids were analyzed by gas chromatography in the plasma of 15 subjects with GDM and 30 healthy control subjects undergoing elective cesarean section and in vein and artery cord blood collected separately. RESULTS—The percentages of AA (20:4 n-6), DHA (22:6 n-3), and total n-6 or n-3 polyunsaturated fatty acids (PUFAs) as well as total PUFAs were lower in umbilical arterial but not in venous plasma of neonates of the GDM versus the control group. CONCLUSIONS—An altered handling or metabolism of long-chain PUFAs by the fetus rather than impaired placental transfer seems to be responsible for the lower proportion of those fatty acids in the plasma of neonates of GDM mothers.

Enhanced circulating retinol and non-esterified fatty acids in pregnancies complicated with intrauterine growth restriction.

IUGR (intrauterine growth restriction) increases the incidence of perinatal complications and, although several placental transport functions have been shown to be altered in pregnancies complicated by IUGR, the mechanism behind it is not well understood. The aim of the present study was to investigate factors in maternal and cord blood plasma from normal and IUGR-complicated pregnancies associated with the body weight of newborns. At the time of Caesarean section, 24 women with IUGR pregnancies were compared with a group of 30 normal controls with AGA (appropriate gestational age) fetuses who were studied at Caesarean section, which took place 5 weeks later than IUGR pregnancies, and also to a group of 25 non-delivered gestational age-matched control pregnant women (AGA-35wk). Maternal plasma retinol, gamma- and alpha-tocopherol, NEFAs (non-esterified fatty acids), and palmitic, palmitoleic, gamma-linolenic and arachidonic acids were higher in women with IUGR pregnancies than in AGA-35wk controls, whereas stearic and alpha-linolenic acids were lower. Smaller differences were found when comparing these variables for IUGR and AGA women. However, umbilical vein plasma gamma-tocopherol, cholesterol, triacylglycerols and NEFAs were higher in the IUGR group than in the AGA group, whereas arachidonic acid was lower. Maternal plasma retinol and NEFAs were the only variables negatively correlated with birthweight when multiple linear regressions were analysed. In conclusion, the increased levels of circulating retinol and NEFAs in maternal plasma are negatively associated with birth and placental weights, which may reflect an impaired placental transfer in IUGR pregnancies. As retinoids are involved in the control of gene transcription, it is proposed that a decrease in placental transfer of retinol could underlie the metabolic dysfunction of IUGR pregnancies.

Growth of fetal lean mass and fetal fat mass in gestational diabetes

This study was carried out to investigate growth indicators of fetal lean mass and fat mass in the second half of the gestational period in pregnancies complicated by gestational diabetes mellitus (GDM) in comparison to normal control pregnancies.

Plasma amino acid concentrations throughout normal pregnancy and early stages of intrauterine growth restricted pregnancy

Objectives: Assessment of maternal plasma amino acids during normal gestation and in early stages of intrauterine growth restriction (IUGR). Study design: Plasma amino acid concentrations were measured in: (1) non-pregnant women (n = 7); (2) normal pregnant women in the first (n = 13), second (n = 17) and third (n = 12) trimester; and (3) pregnant women in the first trimester with later development of IUGR (n = 8). Amino acid levels were quantified by electrochemical detection in a reversed-phase high-performance liquid chromatography (HPLC) system. Results: The levels of most essential and non-essential amino acids changed markedly in the first trimester during normal pregnancy and thereafter remained almost constant. In the first trimester of IUGR, a number of both essential and non-essential amino acids were significantly different from those observed in normal pregnancies, with values more similar to those observed in non-pregnant women. Conclusions: Levels of most maternal amino acids decrease and some increase during early gestation reflecting a metabolic adaptation that occurs in normal pregnancies. Pregnancies that later develop IUGR show a lack of these adaptations for a significant number of both essential and non-essential amino acids, suggesting a lack of adaptation.

The Placenta and Human Developmental Programming: Clinical causes and aspects of placental insufficiency

This chapter uses new epidemiological data to examine the role of materno-placental interactions in initiating chronic disease in the offspring. The size, weight and shape of the placenta are all subject to wide variations. Its size reflects its ability to transfer nutrients. In humans, placental growth responds to maternal influences. Maternal anemia and high maternal body mass index are associated with a high placental weight to birth weight ratio. The observations on hypertension established that the relation between placental size/shape and fetal programming depend on the mother. There are similar materno-placental interactions in the programming of coronary heart disease. Growth of the placental surface is polarized from the time of implantation. The human fetus may attempt to compensate for undernutrition by expansion of the placental surface along its minor axis. The maternal/ placental programming of chronic disease differs in boys and girls.

Relationship between in utero sonographic evaluation and subcutaneous plicometry after birth in infants with intrauterine growth restriction: an exploratory study

BackgroundIntrauterine growth restriction (IUGR) is associated with several medical complications before and after delivery. The aim of this study was to evaluate the concordance between the fetal ultrasonographic measurement of subcutaneous tissue thicknesses and the skinfold thicknesses assessment in intrauterine growth restricted newborns.MethodsWe designed an exploratory study. Fetal ultrasonographic measurement of subcutaneous tissue thicknesses, according to Bernsteins and Galans method, and neonatal skinfold thicknesses were evaluated in 13 intrauterine growth restricted newborns within 4 hours before delivery and on the first day of life, respectively. Concordance between fetal and neonatal measurements was assessed using the Lins correlation coefficient and the Bland-Altman method.ResultsThe data obtained by the measurements of neonatal skinfold thicknesses was significantly correlated with the prenatal measurements (Lins coefficients, arm: 0.60; subscapular: 0.72; abdomen: 0.51). Bland-Altman analysis showed moderate agreement between the fetal ultrasonographic measurement of subcutaneous tissue thicknesses and the neonatal skinfold thicknesses assessment.ConclusionsThe present study provides preliminary evidence that fetal sonographic measurements may represent additional indices of intrauterine growth restriction.

WS02: Prenatal diagnosis WS02‐01Sonographic measurement of fetal subcutaneous tissue of gestational diabetic mothers: a new criteria for therapy

Objective