Early Human Development, 29 (1992) l-4 Elsevier Scientific Publishers Ireland Ltd.
Presidential Address
Progress and development of fetal medicine Shoichi Sakamoto Fetal care was initially developed to prevent fetal disorders by improving obstetrical care related to labor and delivery. It became clear that neonatal care, in collaboration with obstetrics and pediatrics, was essential in obtaining better results in newborn infants which led to the establishment of Perinatal Medicine. Since then, a quarter of a century has passed. Perinatal Medicine has achieved tremendous progress in safety care for mother and child. Furthermore, as neonatal care developed to neonatology, fetal therapy is now becoming a new scientific field as fetal medicine. In order to further develop the area of fetal science, the progress of fetal medicine is the major subject of discussion in this proceedings volume. Development of perinatology
Experiments in perinatal medicine, such as pathophysiology of the fetus and neonatal hypoxia and metabolic analysis of thermogenesis of neonates were potentially carried out during the sixties. Perinatal medicine was initially established in Europe. The term ‘Perinatology’ was also first used at the First European Congress which Professor Saling, Professor Rooth and other outstanding people collaborated and organized. In the eighties, the Asia-Oceania Federation of Perinatology was established in Singapore; Professor Ratnam and Professor Thorburn greatly contributed to this Foundation. In Japan, we founded a neonatal society in 1965. The members of this society were almost equal in numbers in obstetricians, pediatricians and, of course, neonatal surgeons. From these members, the Japanese Society of Perinatology was founded in 1983 as a study group of perinatology with a very limited number of members. Today, I am most grateful to see that the First International Congress has over 1500 participants and more than 500 presentations. Progress in fetal medicine
Progress in fetal therapy, can be divided into three phases according to therapeutic objectives. The first decade, 1965-1975, is defined as a period of fetal emergency care. Many trials were concentrated on diagnosis of fetal distress and resuscitation of newborn infants. The following decade, 1975-1985, was a period of long term management of abnormal fetuses during pregnancy. An introduction of ultrasonographic observation brought us new diagnostic techniques in fetal inspection. 0378-3782/92/%05.00 0 1992 Elwier Printed and Published in Ireland
Scientific Publishers Ireland Ltd.
2
This decade, from 1985 to-date, is an era of a new frontier in fetal therapy in which we can apply individualized diagnostic measures and therapeutic devices to different type of fetal disorders. Establishment of fetal emergency care Fetal emergency care was established by the progress in fetal monitoring. Cardiotocography and acid base determination of fetal blood gave a very accurate diagnosis of fetal distress. Biochemical analysis of maternal hormone secretion and blood enzymatic distribution also provided criteria for placental dysfunction. These led to diagnosing chronically affected fetuses. Therapeutic effects, caused by oxygen inhalation and maternal infusion therapy, could be satisfactorily evaluated and gave a more accurate timing of emergency care in the fetus. However, caution against unnecessary management due to over-diagnosis was claimed elsewhere. In this period, diagnostic criteria for fetal distress by different methods were proposed by distinguished researchers, such as Professor Caldeyro-Barcia, Professor Edward Hon and Professor E. Saling. Long term management of fetus in utero The second decade of progress in perinatology was defined between 1975-1985. Progress in ultrasonic diagnosis of the fetus brought the second advanced stage in fetal care. Abnormalities in fetal growth could be accurately diagnosed by fetometry. In addition, cross sectional view of the fetus gave us new indications for therapeutic measures, such as fetal surgery, fetal biopsy, etc. Blood flow determination by Doppler ultrasound enabled us to monitor circulatory conditions in the fetus. These contributed to long-term management of the fetus in utero. Congenital hydrocephalus develops rapidly around the 28th week. Close observation of cerebral thickness gives the exact timing of induction of labor. Radical neurosurgery to construct permanent drainage followed by delivery saves the baby from mental disorders. Accurate diagnosis of placenta previa and precise determination of fetal growth could be easily obtained by ultrasonography. Intrauterine blood transfusion or even an exchange transfusion through the umbilical vein when blood incompatibility occurs, could be carried out by guided catheterization under ultrasonography. Genetic diagnosis such as amniocentesis and chorionic villi sampling (CVS), developed during this period, was also one of the remarkable progresses in fetal medicine. Some of the inborn errors of metabolism which affect the mental development of the newborn, such as methyl maronic acidemia or galactosemia, can be treated by maternal administration of cyanocobalamin or a low galactose diet for the mother. Typical medical intervention in handicapped fetus of hydrocephalus, is described as an example. Enlargement of BPD was clearly shown ultrasonographically. Progress of ventricular dilatation and thinning of cerebral cortex by CT were carefully monitored along with fetal growth and maturation.
Uur case was born at 36 weeks of gestation by cesarean section followed by neurosurgery of continuous drainage. Both the fetus’ maturation tolerance to surgical stress and the prognostic limitation of the ventricular enlargement were carefully taken into consideration in determining the time of delivery. By CT scanning, performed one week after surgery, remarkable reduction in ventricular size was noted. The baby recovered smoothly and obtained normal mental development at the age of one. Individualization
in fetal therapy
Advances in bioengineering and molecular biology in recent years contribute greatly to the scientific bases of perinatal medicine. Feto-maternal interaction of growth factors and endothelial functions of chorionic villi gave basic consideration of pathogenesis of IUGR. Feto-maternal interaction was clearly demonstrated by IGF-1 regulation in relation in fetal growth. Production of IGF-1 is switched over from the maternal liver to the placenta. Activity of IGF-1 in the placental environment is regulated by the autocrine function of the villi and paracrine function of villi and decidua. The hPL and placental GH stimulate IGF-1 and its binding protein production in the maternal liver. Binding protein is also regulated by protaese from decidua. These facts suggest that duplicate cycle for IGF-1 regulation functions during pregnancy. Fetal growth factors are independent of the maternal side; however, they show their activity substrate dependency by maternal transport of nutrients. IGFs mainly have three types of structure, IGF-1,2,3 and they have different functions, respectively. Other growth factors concerning the fetal growth should be studied carefully. Coagulation and Fbrinolysis system-thrombomoduline
This system is another example of the new approach to analyze placental circulation in PIH. It became clear that trophoblast has an endothelial function inaintaining smooth blood circulation in the intervillous space, in which most slow and complicated blood streams exist and easily forms infarction during abnormal conditions, such as PIH. Our data clearly indicated decreased trophoblastic thrombomodulin activity in PIH, which referred to endothelial function. This is one of the explanations for the fact that remarkable IUGR takes place in severe PIH. Endothelial function in pregnancy is also an important field to study. Fetal surgery
Direct therapeutic approach to the fetus, such as catheter replacement and experimental trial of gene manipulation, may lead to radical treatment in utero. Open fetal surgery may lead to complete correction of fetal anomalies. Direct catheter replacement to half delivered fetuses with urethral obstruction at the thirtieth week through incised uterine window was first performed in Japan by Dr Chiba in Osaka in 1990. The window was closed and the amnion was supplied through a catheter. The baby was successfully managed for a considerable period in utero after surgery. Radical urethral reconstruction was performed in the neonatal period. This evidences show that fetal medicine is obtaining general consensus for clinical use.
4
Several years age, the International Symposium ‘Fetus as a Patient’ was held with anticipation and hope of all perinatologists. Fetal medicine, started from emergency care of fetal distress 25 years ago, is now able to apply total medi-care to the fetus. Our hope symbolized in ‘Fetus as a Patient’ is now being realized. Finally, I would like to conclude by saying . . . Whenever, wherever, we have our hopes and dreams, they will certainly be realized and bring a brighter future in perinatal medicine.
Presidential Address
Progress and development of fetal medicine Shoichi Sakamoto Fetal care was initially developed to prevent fetal disorders by improving obstetrical care related to labor and delivery. It became clear that neonatal care, in collaboration with obstetrics and pediatrics, was essential in obtaining better results in newborn infants which led to the establishment of Perinatal Medicine. Since then, a quarter of a century has passed. Perinatal Medicine has achieved tremendous progress in safety care for mother and child. Furthermore, as neonatal care developed to neonatology, fetal therapy is now becoming a new scientific field as fetal medicine. In order to further develop the area of fetal science, the progress of fetal medicine is the major subject of discussion in this proceedings volume. Development of perinatology
Experiments in perinatal medicine, such as pathophysiology of the fetus and neonatal hypoxia and metabolic analysis of thermogenesis of neonates were potentially carried out during the sixties. Perinatal medicine was initially established in Europe. The term ‘Perinatology’ was also first used at the First European Congress which Professor Saling, Professor Rooth and other outstanding people collaborated and organized. In the eighties, the Asia-Oceania Federation of Perinatology was established in Singapore; Professor Ratnam and Professor Thorburn greatly contributed to this Foundation. In Japan, we founded a neonatal society in 1965. The members of this society were almost equal in numbers in obstetricians, pediatricians and, of course, neonatal surgeons. From these members, the Japanese Society of Perinatology was founded in 1983 as a study group of perinatology with a very limited number of members. Today, I am most grateful to see that the First International Congress has over 1500 participants and more than 500 presentations. Progress in fetal medicine
Progress in fetal therapy, can be divided into three phases according to therapeutic objectives. The first decade, 1965-1975, is defined as a period of fetal emergency care. Many trials were concentrated on diagnosis of fetal distress and resuscitation of newborn infants. The following decade, 1975-1985, was a period of long term management of abnormal fetuses during pregnancy. An introduction of ultrasonographic observation brought us new diagnostic techniques in fetal inspection. 0378-3782/92/%05.00 0 1992 Elwier Printed and Published in Ireland
Scientific Publishers Ireland Ltd.
2
This decade, from 1985 to-date, is an era of a new frontier in fetal therapy in which we can apply individualized diagnostic measures and therapeutic devices to different type of fetal disorders. Establishment of fetal emergency care Fetal emergency care was established by the progress in fetal monitoring. Cardiotocography and acid base determination of fetal blood gave a very accurate diagnosis of fetal distress. Biochemical analysis of maternal hormone secretion and blood enzymatic distribution also provided criteria for placental dysfunction. These led to diagnosing chronically affected fetuses. Therapeutic effects, caused by oxygen inhalation and maternal infusion therapy, could be satisfactorily evaluated and gave a more accurate timing of emergency care in the fetus. However, caution against unnecessary management due to over-diagnosis was claimed elsewhere. In this period, diagnostic criteria for fetal distress by different methods were proposed by distinguished researchers, such as Professor Caldeyro-Barcia, Professor Edward Hon and Professor E. Saling. Long term management of fetus in utero The second decade of progress in perinatology was defined between 1975-1985. Progress in ultrasonic diagnosis of the fetus brought the second advanced stage in fetal care. Abnormalities in fetal growth could be accurately diagnosed by fetometry. In addition, cross sectional view of the fetus gave us new indications for therapeutic measures, such as fetal surgery, fetal biopsy, etc. Blood flow determination by Doppler ultrasound enabled us to monitor circulatory conditions in the fetus. These contributed to long-term management of the fetus in utero. Congenital hydrocephalus develops rapidly around the 28th week. Close observation of cerebral thickness gives the exact timing of induction of labor. Radical neurosurgery to construct permanent drainage followed by delivery saves the baby from mental disorders. Accurate diagnosis of placenta previa and precise determination of fetal growth could be easily obtained by ultrasonography. Intrauterine blood transfusion or even an exchange transfusion through the umbilical vein when blood incompatibility occurs, could be carried out by guided catheterization under ultrasonography. Genetic diagnosis such as amniocentesis and chorionic villi sampling (CVS), developed during this period, was also one of the remarkable progresses in fetal medicine. Some of the inborn errors of metabolism which affect the mental development of the newborn, such as methyl maronic acidemia or galactosemia, can be treated by maternal administration of cyanocobalamin or a low galactose diet for the mother. Typical medical intervention in handicapped fetus of hydrocephalus, is described as an example. Enlargement of BPD was clearly shown ultrasonographically. Progress of ventricular dilatation and thinning of cerebral cortex by CT were carefully monitored along with fetal growth and maturation.
Uur case was born at 36 weeks of gestation by cesarean section followed by neurosurgery of continuous drainage. Both the fetus’ maturation tolerance to surgical stress and the prognostic limitation of the ventricular enlargement were carefully taken into consideration in determining the time of delivery. By CT scanning, performed one week after surgery, remarkable reduction in ventricular size was noted. The baby recovered smoothly and obtained normal mental development at the age of one. Individualization
in fetal therapy
Advances in bioengineering and molecular biology in recent years contribute greatly to the scientific bases of perinatal medicine. Feto-maternal interaction of growth factors and endothelial functions of chorionic villi gave basic consideration of pathogenesis of IUGR. Feto-maternal interaction was clearly demonstrated by IGF-1 regulation in relation in fetal growth. Production of IGF-1 is switched over from the maternal liver to the placenta. Activity of IGF-1 in the placental environment is regulated by the autocrine function of the villi and paracrine function of villi and decidua. The hPL and placental GH stimulate IGF-1 and its binding protein production in the maternal liver. Binding protein is also regulated by protaese from decidua. These facts suggest that duplicate cycle for IGF-1 regulation functions during pregnancy. Fetal growth factors are independent of the maternal side; however, they show their activity substrate dependency by maternal transport of nutrients. IGFs mainly have three types of structure, IGF-1,2,3 and they have different functions, respectively. Other growth factors concerning the fetal growth should be studied carefully. Coagulation and Fbrinolysis system-thrombomoduline
This system is another example of the new approach to analyze placental circulation in PIH. It became clear that trophoblast has an endothelial function inaintaining smooth blood circulation in the intervillous space, in which most slow and complicated blood streams exist and easily forms infarction during abnormal conditions, such as PIH. Our data clearly indicated decreased trophoblastic thrombomodulin activity in PIH, which referred to endothelial function. This is one of the explanations for the fact that remarkable IUGR takes place in severe PIH. Endothelial function in pregnancy is also an important field to study. Fetal surgery
Direct therapeutic approach to the fetus, such as catheter replacement and experimental trial of gene manipulation, may lead to radical treatment in utero. Open fetal surgery may lead to complete correction of fetal anomalies. Direct catheter replacement to half delivered fetuses with urethral obstruction at the thirtieth week through incised uterine window was first performed in Japan by Dr Chiba in Osaka in 1990. The window was closed and the amnion was supplied through a catheter. The baby was successfully managed for a considerable period in utero after surgery. Radical urethral reconstruction was performed in the neonatal period. This evidences show that fetal medicine is obtaining general consensus for clinical use.
4
Several years age, the International Symposium ‘Fetus as a Patient’ was held with anticipation and hope of all perinatologists. Fetal medicine, started from emergency care of fetal distress 25 years ago, is now able to apply total medi-care to the fetus. Our hope symbolized in ‘Fetus as a Patient’ is now being realized. Finally, I would like to conclude by saying . . . Whenever, wherever, we have our hopes and dreams, they will certainly be realized and bring a brighter future in perinatal medicine.
