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Perinatal outcome and the placenta
8
FM3.04 FETAL FM3.04.01 OVERVIEW F. Belgium
WEDNESDAY,
ORIGINS
OF ADULT DISEASE
University Hospital Gasthuisberg,
Leuven,
There is evidence that an abnormal intra-uterine environment has long lasting consequences in adult life. However, when we published in 1979 for the first time in the international litterature that an abnormal intra-uterine environment could induce consequences in later life, we felt major septicism at that time. At this moment, epidemiologic data show that intra-uterine growth restriction is related with insulin resistance in adult life expressed as vascular diseases and type II diabetes. Asymetric fetal macrosomia may be responsible for reduced insulin secretion in adult life. Animal experiments may explain some of the working mechanisms. Severe diabetes or malnutrition during pregnancy in the rat induces fetal growth restriction; at adulthood these offspring show insulin resistance and vascular dysfunction. We suggest that an underdevelopment during fetal life of insulin receptors may be operational. There is also evidence that oxidative stress is involved. Mild diabetes in the rat induces fetal macrosomia, in adult life there is a reduced insulin secretion. It is clear that the maternally derived changes in fetal plasma composition (glucose, amino-acids, fatty-acids) certainly influence the development and function of the fetal endocrine pancreas, but they affect other organs and functions as well (kidney, hypothalamus, endothelium, etc). The consequences are mostly seen at older age, since the vitality of the organism is reduced and can not more compensate for these alterations.
FM3.04.02 PLACENTAL GLUCOCORTICOID METABOLISM: AN ENDOCRINE LINK WITH THE <> M. D. KilbL Birmingham Women’s Hospital, Birmingham, United Kingdom Babies who are born small at birth and continue to be small during infancy are known to be at increased risk of developing cardiovascular disease in adult life. It is thought that these adult diseases are <> by an inadequate supply of nutrients or oxygen in-utero. As well as birthwieght, placental weight has also been correlated with adult cardiovascular disease, independently of birthweight. Babies with a placenta that is disproportionately large (in relation to their birthweights), are at increased risk of cardiovascular disease also. In animals, fetal hypercortisolaemia is associated with impaired fetal growth. The placenta is the site of production of a unique enzyme which metabolises cortisol to relatively inactive, cortisone, called llfl hydroxysteroid dehydrogenase 2. We have demonstrated that placental weight is directly proportional to the activity of this enzyme in the placenta and that in severely growth restricted babies, the llfl HSD2 expression is significantly reduced, especially if associated with placental vascular disease. Also, in <> pregnancies in which amniocentesis has been performed and fetal size estimated using ultrasound, there appears to be an inverse relationship between amniotic fluid cortisol concentration and fetal size (independent of gestational age). This provides further evidence of an association between placentaufetal weight ratio and fetal cortisol metabolism in-utero. Such evidence, indicates that the placenta is more than a <> for nutrients and oxygen. It has the ability to at as an endocrine organ and data presented in this presentation further expands on this hypothesis.
FM3.04.03 PERINATAL OUTCOME AND THE PLACENTA TT Department of Obstetrics & Gynaecology, The University Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.
of
There is now evidence of an association between an increased placental weight to birthweight ratio (placental ratio) with cardiovascular complications and diabetes mellitus in adulthood. Yet there is scanty information on the relationship between the placental size or pathology
SEPTEMBER
6
with the perinatal outcome, despite that fact that the placenta has been referred to as the “diary of the pregnancy”. Placental infarction and chronic villitis has been associated with fetal growth restriction in preterm and term infants. In the preterm infant, the presence of chorionic and umbilical vasculitis, which are thought to represent pre-existing infection, are associated with increased risk of intraventricular haemorrhage independent of confounders. While the placental weight is correlated with infant birthweight, a disproportionately heavier placenta, as reflected by an increased placental ratio, can be found with the smallfor-gestational age (SGA) newborns, as well as maternal anaemia and gestational diabetes mellitus. An “overweight” placenta is associated with evidence of acute or subacute antenatal hypoxia, including low Apgar scores, respiratory distress, neurological abnormalities, and neonatal death, especially in infants born before 35 weeks. Some of the neurological abnormalities persisted into childhood. Most recently, it has been shown that in SGA infants without major anomalies, a high placental ratio was due to increased placental weight and decreased birthweight in the absence of any difference in maternal characteristics or antenatal complications. Furthermore, the infants with a high placental ratio had increased incidence of meconium stained liquor, hypocalcaemia, hypomagnesaemia, phototherapy for neonatal jaundice, and sepsis. While histological examination of the placenta may not be feasible as a routine in many centres, the placental weight is usually available soon after childbirth. Further studies are warranted to determine whether this information may help to identify not only subjects who are at risk of diseases in adulthood, but also newborns who may have increased morbidity in infancy and childhood.
FM3.04.04 FETAL CARDIOVASCULAR PROGRAMMING K. Marsal, H. Gardiner, .I. Brodszki, Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden The reactive fetus responds to severe uteroplacental insufficiency by reducing flow to non-essential organs, and increasing flow to the cerebral circulation, heart and adrenal glands. Obstructed areas within the placenta result in increased impedance and may even cause reversal of flow back into the fetal arterial circulation at end-diastole thus increasing the ventricular afterload and compromising fetal cardiovascular function. We have studied the hypothesis that abnormal arterial flow patterns in SGA fetuses program early vascular development which, by a process of amplification, may result in adult onset hypertension. Fetal cardiovascular function was examined using ultrasound. Pulse waveform and pulse wave velocity in the thoracic descending aorta was investigated using a phase-locked echo-tracking system. Spectral pulsed Doppler ultrasound was used for examination of aortic, middle cerebral arterial and intracardiac blood flow velocities and the velocity waveform was evaluated. The dimensions of the descending aorta in growth restricted fetuses were equivalent to younger, normally grown fetuses of similar mean fetal weight. SGA fetuses had lower ventricular diastolic filling than normal fetuses and did not show gestational increase in fractional shortening. The maximal velocity through the aortic valve was less in growth restricted fetuses, but there were no significant differences in the pulmonary artery maximal velocity. The pulse wave characteristics of the descending aorta differed in SGA fetuses (lower late decremental velocity and reduced relative pulse amplitude). The differences in the vascular biophysical properties observed in growth restricted fetuses support the hypothesis that vascular remodelling occurs and attempts to maintain stable arterial wall stress. However, whilst fetal adaptive mechanisms may aid survival they may result in cerebral, and vascular abnormalities.
ON3.03.01 OVERVIEW OF CERVICAL SCREENING WORLDWIDE Salonev Nazeer, Clinique de StCrilitC et d‘Endocrinologie GynCcologique, Geneva, Switzerland Cervical cancer is perhaps the most preventable major form of cancer to date, yet 450 000 women develop invasive disease which causes more than 200 000 deaths each year, globally. Developing countries account for 80% of the cervical cancer disease burden but only 5% of the global resources for cancer control. In these
FM3.04 FETAL FM3.04.01 OVERVIEW F. Belgium
WEDNESDAY,
ORIGINS
OF ADULT DISEASE
University Hospital Gasthuisberg,
Leuven,
There is evidence that an abnormal intra-uterine environment has long lasting consequences in adult life. However, when we published in 1979 for the first time in the international litterature that an abnormal intra-uterine environment could induce consequences in later life, we felt major septicism at that time. At this moment, epidemiologic data show that intra-uterine growth restriction is related with insulin resistance in adult life expressed as vascular diseases and type II diabetes. Asymetric fetal macrosomia may be responsible for reduced insulin secretion in adult life. Animal experiments may explain some of the working mechanisms. Severe diabetes or malnutrition during pregnancy in the rat induces fetal growth restriction; at adulthood these offspring show insulin resistance and vascular dysfunction. We suggest that an underdevelopment during fetal life of insulin receptors may be operational. There is also evidence that oxidative stress is involved. Mild diabetes in the rat induces fetal macrosomia, in adult life there is a reduced insulin secretion. It is clear that the maternally derived changes in fetal plasma composition (glucose, amino-acids, fatty-acids) certainly influence the development and function of the fetal endocrine pancreas, but they affect other organs and functions as well (kidney, hypothalamus, endothelium, etc). The consequences are mostly seen at older age, since the vitality of the organism is reduced and can not more compensate for these alterations.
FM3.04.02 PLACENTAL GLUCOCORTICOID METABOLISM: AN ENDOCRINE LINK WITH THE <
FM3.04.03 PERINATAL OUTCOME AND THE PLACENTA TT Department of Obstetrics & Gynaecology, The University Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.
of
There is now evidence of an association between an increased placental weight to birthweight ratio (placental ratio) with cardiovascular complications and diabetes mellitus in adulthood. Yet there is scanty information on the relationship between the placental size or pathology
SEPTEMBER
6
with the perinatal outcome, despite that fact that the placenta has been referred to as the “diary of the pregnancy”. Placental infarction and chronic villitis has been associated with fetal growth restriction in preterm and term infants. In the preterm infant, the presence of chorionic and umbilical vasculitis, which are thought to represent pre-existing infection, are associated with increased risk of intraventricular haemorrhage independent of confounders. While the placental weight is correlated with infant birthweight, a disproportionately heavier placenta, as reflected by an increased placental ratio, can be found with the smallfor-gestational age (SGA) newborns, as well as maternal anaemia and gestational diabetes mellitus. An “overweight” placenta is associated with evidence of acute or subacute antenatal hypoxia, including low Apgar scores, respiratory distress, neurological abnormalities, and neonatal death, especially in infants born before 35 weeks. Some of the neurological abnormalities persisted into childhood. Most recently, it has been shown that in SGA infants without major anomalies, a high placental ratio was due to increased placental weight and decreased birthweight in the absence of any difference in maternal characteristics or antenatal complications. Furthermore, the infants with a high placental ratio had increased incidence of meconium stained liquor, hypocalcaemia, hypomagnesaemia, phototherapy for neonatal jaundice, and sepsis. While histological examination of the placenta may not be feasible as a routine in many centres, the placental weight is usually available soon after childbirth. Further studies are warranted to determine whether this information may help to identify not only subjects who are at risk of diseases in adulthood, but also newborns who may have increased morbidity in infancy and childhood.
FM3.04.04 FETAL CARDIOVASCULAR PROGRAMMING K. Marsal, H. Gardiner, .I. Brodszki, Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden The reactive fetus responds to severe uteroplacental insufficiency by reducing flow to non-essential organs, and increasing flow to the cerebral circulation, heart and adrenal glands. Obstructed areas within the placenta result in increased impedance and may even cause reversal of flow back into the fetal arterial circulation at end-diastole thus increasing the ventricular afterload and compromising fetal cardiovascular function. We have studied the hypothesis that abnormal arterial flow patterns in SGA fetuses program early vascular development which, by a process of amplification, may result in adult onset hypertension. Fetal cardiovascular function was examined using ultrasound. Pulse waveform and pulse wave velocity in the thoracic descending aorta was investigated using a phase-locked echo-tracking system. Spectral pulsed Doppler ultrasound was used for examination of aortic, middle cerebral arterial and intracardiac blood flow velocities and the velocity waveform was evaluated. The dimensions of the descending aorta in growth restricted fetuses were equivalent to younger, normally grown fetuses of similar mean fetal weight. SGA fetuses had lower ventricular diastolic filling than normal fetuses and did not show gestational increase in fractional shortening. The maximal velocity through the aortic valve was less in growth restricted fetuses, but there were no significant differences in the pulmonary artery maximal velocity. The pulse wave characteristics of the descending aorta differed in SGA fetuses (lower late decremental velocity and reduced relative pulse amplitude). The differences in the vascular biophysical properties observed in growth restricted fetuses support the hypothesis that vascular remodelling occurs and attempts to maintain stable arterial wall stress. However, whilst fetal adaptive mechanisms may aid survival they may result in cerebral, and vascular abnormalities.
ON3.03.01 OVERVIEW OF CERVICAL SCREENING WORLDWIDE Salonev Nazeer, Clinique de StCrilitC et d‘Endocrinologie GynCcologique, Geneva, Switzerland Cervical cancer is perhaps the most preventable major form of cancer to date, yet 450 000 women develop invasive disease which causes more than 200 000 deaths each year, globally. Developing countries account for 80% of the cervical cancer disease burden but only 5% of the global resources for cancer control. In these