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

OBJECTIVES: 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. METHODS: Forty-three control and 171 GDM pregnancies were followed longitudinally by ultrasound examinations, measuring both traditional biometric parameters and six non-traditional parameters for the evaluation of lean and fat mass. A mixed linear model derived from the log-Count function was used to model fetal growth and to make comparisons between groups. Factor analysis was used to evaluate the associations between gestational diabetes and fetal size and fetal fat/lean mass ratios. RESULTS: A total of 506 scans were obtained in the 214 pregnancies, a mean of 2.4 scans per pregnancy (range 2-5). Maternal age, prepregnancy weight and body mass index were significantly higher in GDM pregnancies. Fetuses of GDM pregnancies showed greater growth, at the same gestational age, for each lean and fat non-traditional parameter, having a significantly greater amount of total tissue mass and a higher fat mass/lean mass ratio, independent of gestational age, in comparison to control pregnancies. CONCLUSIONS: A non-invasive, repeatable evaluation of fetal body composition in utero could represent a useful method for the early detection of growth abnormalities and for direct estimation of the fetal metabolic status.

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. POPULATION AND METHODS: Maternal arterial and umbilical venous and arterial blood samples were collected from 37 normal (N) and 38 pregnancies complicated by gestational diabetes (GDM) at the time of caesarean section. MAIN OUTCOME MEASURES: Respiratory gases, acid-base balance, lactate and glucose concentrations were measured. RESULTS: Both fetal and placental weights were significantly increased in GDM compared to N pregnancies, despite similar gestational age. Maternal biochemical parameters were similar in N and GDM but GDM fetuses were significantly more hypoxic (O2 saturation: N 63.2+/-13.9; GDM 53.8+/-14.6%, P<0.01; O2 content: N 5.5+/-1.4; GDM 4.8+/-1.2 mmol/l, P<0.05). Glucose (N 3.4+/-0.5, GDM 3.9+/-1.2 mmol/l, P<0.05) and lactate (N 1.32+/-0.49; GDM 1.64+/-0.75 mmol/l, P<0.05) concentrations were significantly increased in the umbilical vein in GDM compared to N fetuses. Placental histology was consistent with altered villous morphology. CONCLUSIONS: Our data indicate that fetuses from gestational diabetic mothers have increased umbilical glucose concentrations despite normal maternal glucose levels and a reduction in oxygen saturation and O2 content together with increased lactate concentration, reflecting altered fetal metabolism. These data suggest that 'good maternal metabolic control' achieved by currently used methods of monitoring glucose control is not sufficient to ensure a normal oxygenation status and metabolic milieu for the fetus in GDM 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.

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.

Foetal and placental weights in relation to maternal characteristics in gestational diabetes.

An increased placental weight has been reported in pregnancies complicated with gestational diabetes (GDM). We have analysed foetal (F) and placental weight (P) and foetal length in 143 consecutive normal (N) and 132 GDM pregnancies in relation to type of treatment and to a number of maternal variables. All N pregnancies had a negative oral glucose challenge test at 24-28 weeks. GDM was diagnosed at 28-32 weeks by a 100-gm, 3-h oral glucose tolerance test (OGTT). Treatment was diet (D: n=82) or diet plus insulin (D+I: n=50) according to self-monitoring of blood glucose. A significant difference was observed between N and GDM pregnancies for maternal age (N=30.6+/-5.38 years; GDM=33.2+/-4.53 years; P< 0.001), pre-pregnancy weight (N=58.2+/-8.0 kg; GDM=63.0+/-12.9 kg; P< 0.001) and BMI (N= 21.9+/-2.63; GDM=24.4+/-4.71;P< 0.001). Foetal weight became significantly higher in the GDM group (N=3274.2+/-296.0 g; GDM=3287.1+/-474.1g; P< 0.05) once correction was made for the significant difference in gestational age between the two groups (N=39.4+/-1.17 weeks; GDM=38.8+/-1.39 weeks; P< 0.001). Significantly higher placental weights (N=561.87+/-91.0 g; GDM=592.2+/-115.8 g;P< 0.01) and significantly lower F/P weight ratios were found in GDM pregnancies (N=5.96+/-1.02; GDM=5.69+/-1.13; P< 0.05). In GDM pregnancies a significantly negative correlation was found between the OGTT response and weights of foetus and placentae at delivery, suggesting that both foetal and placental growth are affected by maternal insulin resistance.

The endocrine and metabolic profile of the growth-retarded fetus.

Intrauterine growth retardation (IUGR) is characterized by the failure of the fetus to grow at a normal rate in utero and is associated with a number of endocrine and metabolic changes. Our knowledge of the placental nutrient supply and the endocrine status of the fetal-placental unit during pregnancies involving IUGR has greatly increased over the past decade as a result of the availability of fetal blood samples obtained under relatively steady state conditions. These studies have provided evidence that the supply of glucose is impaired only under severe conditions, whereas placental transfer of amino acids is reduced even in fetuses with normal oxygenation and feto-placental blood flow. Moreover, significant in utero relationships have been reported between fetal weight and circulating levels of growth factors such as insulin-like growth factor-I and leptin. When measured per kg fetal weight, however, levels of leptin are significantly higher in growth-retarded fetuses, with abnormal feto-placental blood flow and reduced oxygen content. The metabolic and endocrine changes observed should be interpreted in relation to the severity of the disease.

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.