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Despite considerable advances in the treatment of diabetes in the past decades, diabetic pregnancies can still be associated with fetal growth disturbances even when an optimized and intensive metabolic control has been achieved. Macrosomia of the fetus is a common and well-known consequence of maternal diabetes with an increased obstetric risk. The increase in fetal fat mass that accounts for the fetal overweight [1] is the result of fetal hyperinsulinism as a consequence of maternal and, therefore, fetal hyperglycaemia [2]. According to the dynamics of fetal growth, macrosomia is caused by metabolic alterations or hyperglycaemic insults predominantly in later stages of pregnancy [3,4]. In contrast diabetes-associated metabolic derangements in the first trimester of pregnancy can lead to malformations [5] and to delayed growth of the developing embryo [6,7]. Whereas the molecular mechanisms underlying embryo malformations have received enormous attention, no data are available to explain early fetal growth delay. Because of the close link between placental and fetal growth, early intrauterine growth delay could be caused by a reduced growth of the pla- Diabetologia (2001) Abstract Aims/hypothesis. Early intrauterine growth delay in diabetes could be caused by a reduced growth of the placenta. Our study investigates whether hyperglycaemia in vitro reduces trophoblast proliferation. Methods. First-trimester trophoblast cell models (BeWo, JAR and JEG-3 choriocarcinoma cells) were cultured for 24 and 48 h with 5.5 mmol/l d-glucose, 25 mmol/l d-glucose (hyperglycaemia) and with an osmotic control. Cell number, total protein and nucleic acid content and mitochondrial activity (tetrazolium salt assay) were measured, the cell cycle analysed (FACS, cyclin B1 levels) and apoptosis (Annexin-V) measured.Results. In BeWo cells hyperglycaemia reduced cell number, protein, nucleic acid and cyclin B1 levels. The reduced G 2 /M and increased G 0 /G 1 population after 24 h reflects growth arrest at G 0 /G 1 . In JAR cells after 24 h the population was arrested in G 0 /G 1 , whereas after 48 h the G 0 /G 1 block was abrogated and the cells were arrested at G 2 /M. The net effect was an unchanged cell number. In JEG-3 cells hyperglycaemia resulted in fewer cells after 24 h but not after 48 h indicating some adaptation. Mitochondrial activity was either stimulated (BeWo) or reduced (JAR, JEG-3) under hyperglycaemia. Some of these effects were also induced by hyperosmolarity alone. Conclusion/interpretation. Hyperglycaemia has the potential to inhibit the proliferation of first-trimester trophoblast cell models. The mechanisms leading to growth arrest and to changes in mitochondrial activity are complex and depend on differentiation. We hypothesise a hyperglycaemia-induced impairment of placental growth in the first trimester of a poorly controlled diabetic pregnancy. [Diabetologia (2001) 44: 209±219]

Objective To define the normal ranges of umbilical cord blood oxygen saturation (SaO,) and acid-base status at birth and to evaluate the effect of gestational age on cord blood values in vigorous newborn infants following spontaneous vaginal birth from a vertex position.Design Prospective study.Setting Department of Obstetrics and Gynaecology, University of Graz, Austria.Sample Cord blood samples from 1281 vigorous newborn infants.Methods Cord blood sampling was performed following on newborn infants following spontaneous vaginal birth in a vertex position. SaO, was measured directly by a spectrophotometer and pH, base excess, pC0, and PO, by a pH/blood-gas analyser. Infants with a 5-minute Apgar score 2 7 were considered vigorous. Subgroups were classified according to the gestational age: preterm, term and postterm (< 37,3742 and > 42 weeks, respectively). ResultsThe median umbilical artery SaO, was 24.3% and the 2.5th centile was as low as 2.7%. The median umbilical artery values were pH = 7-25, base excess = -4.3 mmol/L and PO, = 16 mmHg. The 2.5th centiles were 7.08, -1 1.1 mmol/L and 5 mmHg, respectively. The median umbilical artery pC0, was 50 mmHg and the 97.5th centile was 75 mmHg. The mean umbilical artery and vein SaO, values were not significantly influenced by gestational age. The umbilical artery SaO, and base excess values were strongly skewed. The mean umbilical artery pH values in preterm infants were higher than in other subgroups. The mean umbilical artery and vein base excess values were lower in post-term newborn infants than in other subgroups.Conclusions The physiological range of oxygen saturation in umbilical cord of vigorous newborn infants at birth is wide and skewed. In contrast to pH and base excess, umbilical cord blood oxygen saturation is not influenced significantly by gestational age at birth.

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