21
Early Human Development, 29 (1992) 21-26 Elsevier Scientific Publishers Ireland Ltd.
EHD 01246
Frontiers in perinatal medicine GGsta Rooth Department
of Pediatrics,
University
of Uppsala
6fre
Slottsgatan
14 C, S-75 310 Uppsala
(Sweden)
summary A few of the topics of particular interest in perinatal medicine such as surfactants, erythropoietin, cordocentesis and computer assisted decision support are briefly reviewed. Asphyxia and oxygen toxicity are discussed as is the increase in the formation of free radicals which is part of reoxygenation. The infinitely larger problem of the poor in developing countries can best be improved - at least partially - by extending family planning techniques universally, otherwise the population explosion will counteract any other improvements. Key words: surfactants; erythropoietin; cordocentesis; hypoxia; free radicals; nonsurgical sterilization; developing countries
Intrwluction Some examples of frontiers in perinatal medicine will be briefly discussed and two topics with which the author has been directly or indirectly involved will be discussed in more detail. Surfactants and respiration In connection with the 1979 World Congress of Obstetrics and Gynaecology in Tokyo, Fujiwara demonstrated for the first time to an international group the dramatic effect of instillation of a surfactant in infants with respiratory distress. As is so often the case, the wide application has proven more complicated than expected and this is still indeed a frontline in perinatal medicine. A more recent approach to the treatment of severe pulmonary insufficiency is liquid ventilation, reported in 1990 by Greenspan and colleagues [l]. Correspondence to: GGsta Rooth, Department of Pediatrics, University of Uppsala, t)fre Slottsgatan 14 C, S-75 310 Uppsala, Sweden.
0378-3782/92/%05.00 0 1992 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland
22
Erytbropoietin Erythropoietin was a major subject of study at the Donner Laboratory of the Lawrence Berkeley Laboratories when the author worked there in 1963 and 1964. Their interest has been maintained and is now becoming most rewarding as important clinical applications are revealed. In 1985 Teramo and coworkers first observed that erythropoietin could be an indicator of fetal hypoxemia, a completely new approach to monitoring this condition [2]. Erythropoietin has also found an application in obstetrics. Thanks to gene technique, this substance is now commercially available and Danko et al. have shown that it can be used to advantage in post delivery anemia [3]. Cordocentesis and fetal interventions It was a major breakthrough when Saling initiated fetal scalp sampling. Today, we can obtain fetal blood before delivery, thanks to cordocentesis, i.e., the puncturing of the umbilical cord. This is, of course, a superior way of assessing fetal anemia and thrombocytopenia. The technique also allows direct chromosomal preparation of a placental biopsy taken simultaneously and can often provide a fetal karyotype the same day. Sothill feels that today cordocentesis could also be an alternative to fetal scalp sampling [4]. For the future he envisages treatment of severe inherited disease by gene therapy. Crossing the border into the unknown he hopes that the study of fetal endocrinology by cordocentesis may improve our understanding of the fetal role in the initiation of labor. Using endoscopy fetal surgery is gaining ground. The most important procedure as yet is the percutaneous catheter insertion to bypass a blockage. Computer assisted decision support Lilford edited a book in 1990 that gives an excellent review of the use of computer technique in obstetrics [5]. For instance, he mentions how computer-stored hospital records may be used for randomized controlled clinical studies. For years we saw several centers analyzing fetal heart rate patterns with computers, but the practical use was limited. In 1989, Dawes et al., were one of the first groups that really made computer assisted analysis of fetal heart rate patterns useful [6]. Their program is now available commercially. Lilford considers the computer assisted decision making of special importance in the future. It enables physicians and/or nurses to use more formal ways of dealing with severe problems than with what is usually called the intuitive approach. It also allows delegation of responsibilities without reducing competence in the decision making. Take the problem of fluid administration of a newborn premature infant. For a long time, Sedin, Hammarlund and coworkers have been studying transepidermal water loss, a complex function of gestational age and postnatal age, among other factors. To compensate, electrolytes and, usually, nutrients must be added to the water. Storing tables in the computer, Sedin et al. have elaborated a program thanks to which a neonatal nurse can initiate appropriate fluid therapy as soon as the infant is in the incubator [7]. The program calls for a
23
check within 1 h by a senior doctor and of course allows him to make whatever changes he deems advisable. Asphyxia, oxygen, hypoxia and oxygen toxicity Asphyxia of the newborn infant is and will remain a major problem in perinatal medicine. Without early and adequate treatment that offers the infant a chance for a successful life, death or debility will ensue. The clinical situation of asphyxia is well known but the biochemical background needs some clarification. It implies oxygen levels so low that the tissue requirements are insufficient, inter alia leading to a metabolic acidosis. However, at first, as soon as the fetal gas exchange is reduced, there is a respiratory acidosis, i.e., increased Pco*. With progression of the metabolic acidosis, the bicarbonate concentration is lowered. Thereby carbon dioxide is produced and Pco2 increases further. It is therefore of primary importance to initiate ventilation immediately after birth in order to decrease PCO, and to increase pH. At the same time, oxygen will be absorbed and the metabolic acidosis will gradually disappear. With near infrared spectroscopy, cot-side information may be obtained about cerebral oxygen saturation and hemodynamics, and with magnetic resonance spectroscopy not only intracellular pH but ATP and other phospho-compounds important for the brain metabolism may be studied. Monitoring of glucose with near infrared spectroscopy and a detailed study of amino acids and enzymes in the brain with magnetic resonance spectroscopy is soon to be available. Gradually, evidence has been brought forward that the greatest harm of hypoxia comes during the reoxygenation and not during the anoxic period. Three different mechanisms resulting from lack of oxygen are at present considered detrimental to the function of the cell. First, as mentioned, acidosis, second, free radicals and third, excitatory amino acids. Free radicals are molecules or atoms with an unpaired electron. These substances usually only exist for microseconds and are very active. As so often occurs in biology they are both good and bad: good, when produced in the macrophage and assist in the killing off of invading bacteria; bad, when they destroy vital cellular membranes. The two important free radicals in this connection are the superoxide radical 0; and the hydroxyl radical OH*, both being formed in the reactions hypoxanthinexanthine-urate. Hypoxanthine can either be recovered via inosine-5-phosphate or further metabolized to xanthine and uric acid. However, all these three reactions require oxygen, and hypoxanthine is therefore the final degradation product during hypoxia. As increased amounts of hypoxanthine are produced during hypoxia and it readily diffuses out of the cells it is probably the best marker for tissue hypoxia. Although it can be readily measured in any research unit, it has so far not been possible to convince the industry to produce a bedside method. The working hypothesis at present is that free radicals destroy the cellular membranes in the lungs, brain, retina or intestine of the premature infants, thus at least partly explaining the pathogenesis of some of the main diseases of prematurity. Experimental studies have shown that the combination of hypoxanthine and high oxygen concentrations is particularly harmful [8]. The generation of free radicals is
24
a function of the multiplication of the oxygen concentration with that of hypoxanthine. During resuscitation of the newborn this is exactly what is being done clinically and several textbooks stress that 100% oxygen should be used. It would not be surprising if a doctor in the United States could be sued because resuscitation was performed with equal parts of air and oxygen. The premature infant might get an iatrogenic disease if 100% oxygen was given because the physician considers this correct, but it would be a legalogenic disease if it were done to prevent a lawsuit. In fact, increased oxygen concentrations are not needed at all. During fetal life the activity in the electron chain is three times as high as a week after birth. Thus the cells will get the amount of oxygen they need even at a low pressure and the production of free radicals is kept at a minimum. In 1957 we published a report [9] on 12 premature infants kept in 15% oxygen until 40 weeks of gestation, without any untoward complications and in 1986 MacMahon et al. did the same in some very low birthweight infants in order to reduce the risk of retinopathy of prematurity [lo]. There is also protection from free radicals by other means than reducing the oxygen concentration: scavengers (e.g., dimethyl sulfoxide), antioxidants, (e.g., vitamin A, C and E) and antioxienzymes, the best known being superoxide dismutase and glutathione peroxidase. Furthermore, xanthine oxidase may be blocked by allopurinol, which is excellent in cases of gout, but not properly studied in the connection of tissue hypoxia. The third mechanism by which at least brain cells may be damaged is the so-called excitatory amino acids, as they increase dramatically in the brain during hypoxia. This is a term used mainly for glutamic and aspartatic acid. By over-exciting neurons, they injure them. In experimental studies Kjellmer et al. have demonstrated a beneficial effect of kynurenic acid, which is a non-specific antagonist [ 111. Further therapeutic possibilities are being discovered. As a result of the cellular injury the 10 OOO-fold concentration gradient between the calcium ion concentration in the interstitium and in the cytosol is greatly reduced. In adult experimental animals it was found that calcium antagonists were beneficial [ 121. Non-surgical abortion and sterilization
Both non-surgical abortion and sterilization have become extremely important realistic possibilities. The best known and most tested abortifacient is a progesterone blocker called RU 486. In France a 96% efficacy rate has been shown since the approval of the drug in 1988 and about 25% of the women in France who seek abortion use this technique. Using two insertions of intrauterine quinacrine pellets in over 10 000 cases of nonsurgical female sterilization, Kessel et al. have, over several years, found a failure rate of 3-5%. An addition of a 50-mg pellet of an antiprostaglandin seems to lower the failure rate [ 131. The cost for the drug and the inserter is only US $1. Perinatal problems in developing countries
Outside of the scientific advances lies a vast territory,
infinitely
larger and un-
25
fathomable in its complexity and which, by its dimension and poverty, defies most attempts for improvement in perinatal medicine. Few frontiers are more difficult to move than those between the rich and the poor, even when, as far too often is seen, the poor live in a rich country. It is helpful to look first at the ethical problems. As physicians responsible for a specific patient, we follow the Geneva Convention of 1949, ‘The health of my patient will be my first consideration.’ The Hippocratic oath, for long a medical guide, states: ‘The regimen I adopt shall be for the benefit of the patients according to my ability and judgment and not for their hurt or other wrong.’ Dealing with the problems of many individuals at the same time the latter oath has different consequences than the Geneva Convention. A prerequisite when dealing with large numbers of patients is the approach of catastrophe medicine, i.e., to sort out those with the best prognosis first and to treat them, leaving the severely wounded until resources allow them to be adequately cared for. Assume that some, as always limited, medical and other humanitarian assistance will be brought into an area where AIDS and malnutrition are both prevalent. The resources should then be used for mothers and children without AIDS and not starved beyond salvation. We must help the strongest to become healthy; otherwise there will be no one there to cultivate the land and tend the cattle, no one to build houses or work to bring revenue into the community. There are too many ants in the ant hill, to use a well known saying. Even China with its rigid birth control has failed to contain the population at 1000 millions. Already and worse to come, we are faced with incalculable numbers of sick, starving women and children. How can we expect such sick mothers, pregnant too young, to produce healthy strong infants who should improve the lot of their community? We simply must limit the number of births. Many women certainly try this the hard way - it is estimated that between 40 and 60 million abortions take place around the world annually. The goal of the Safe Motherhood Initiative for the year 2000 is to reduce maternal mortality by 50%. It sounds simplistic, but the safest way of accomplishing this is to reduce the pregnancies by half. We must all, wherever we work, actively support the recent International Federation of Gynecology and Obstetrics (FIGO) resolution stating that the knowledge as regards family planning and maternal and child health care is already available and that it is a question of local willpower more than of economic ease and scientific and technical novelties for this to improve. We are in many parts of the world faced with the problems expressed by Professor Harrison in Nigeria ‘African women want to have as many children as possible because it makes sense to do so under the conditions in which most of our people live’. Add to this two other factors: in some societies the men insist that their women should produce a child each year so that everyone can see that they are still men; in others, parents feel their families are incomplete without a son. Having only daughters, they feel compelled to beget more children. With the predicted pop&+ tion increase in 2025, at least 18 countries will have a population of more than 100 million; mega cities will contain 20 million. How can problems of air, water and food, not to speak of sewage, be solved for such masses? How can, as predicted, more than 100 million live along the Nile in Egypt?
26
References 1 Greenspan, J.S., Wolfson, M.R., Rubenstein, SD. and Shaffer T. (1990): Liquid ventilation of human preterm neonates. J. Pediatr., 177, 106-l 11. 2 Teramo, K.A., Widness, J.A., Clemonds, G.K., et al. (1987): Amniotic fluid erythropoietin correlates with umbilical plasma erythropoietin in normal and abnormal pregnancy. Obstet. Gynecol., 69, 710-716. 3 Danko, J., Huch, R. and Huch, A. (1990): Epoetin alfa for treatment of postpartum anaemia. Lancet, 1, 737-738. Sothill, P.W. (1989): Cordocentesis: Role in Assessment of Fetal Condition. Clin. Perinatol., 16, 755-770. Lilford, R.J. Bailibre’s Clinical Obstetrics and Gynaecology, Vol. 4, No. 4. Dawes, G.S., Houghton, C.R.S., Redman, C.W.G. and Visser, G.H. A. ( 1982): Pattern of the normal human fetal heart rate. Br. J. Obstet. Gynaecol., 89, 276-284. Sedin, G., Groth, T., Hammarlund, K. and Seidel, A. (1990): A knowledge based adviser for fluid therapy in the neonatal period. In: Computers and Perinatal Medicine, pp. 55-63. Editors: K. Maedel et al. Elsevier Science Publishers, Amsterdam. 8 Saugstad, O.D., Hallman, M., Abraham, J. (1984): Plasma hypoxanthine levels in newborn infants: A specific indicator of hypoxia. Pediatr. Res., 18, 501. 9 Sjiistedt, S. and Rooth, G. (1957): Low oxygen tension in the management of newborn infants. Arch. Dis. Child., 32, 397-400. ,lO MacMahon, I., Fleming, P.J., Speidel, B.I. and Dunn, P.M. (1986): Retinopathy of prematurity. Br. J. Obstet. Gynaecol., 93, 361-363. 11 Kjellmer, I. (1991): Etiology and pathophysiology of postasphyxial brain damage. Int. J. Tech. Assess Health Care, 7 Suppl. 1, 106-109. 12 Siesjo, B.K. (1981): Cell damage in the brain: a speculative synthesis. J. Cereb. Blood Flow Metab., 1, 155-185. 13 Kessel, E., Zipper, J. and Mumford, S. (1990): The Quinacrine Pellet Method for Nonsurgical Female Sterilization: A Collection of Background Material. Center for Research on Population and Security, Research Triangle Park, NC.
Early Human Development, 29 (1992) 21-26 Elsevier Scientific Publishers Ireland Ltd.
EHD 01246
Frontiers in perinatal medicine GGsta Rooth Department
of Pediatrics,
University
of Uppsala
6fre
Slottsgatan
14 C, S-75 310 Uppsala
(Sweden)
summary A few of the topics of particular interest in perinatal medicine such as surfactants, erythropoietin, cordocentesis and computer assisted decision support are briefly reviewed. Asphyxia and oxygen toxicity are discussed as is the increase in the formation of free radicals which is part of reoxygenation. The infinitely larger problem of the poor in developing countries can best be improved - at least partially - by extending family planning techniques universally, otherwise the population explosion will counteract any other improvements. Key words: surfactants; erythropoietin; cordocentesis; hypoxia; free radicals; nonsurgical sterilization; developing countries
Intrwluction Some examples of frontiers in perinatal medicine will be briefly discussed and two topics with which the author has been directly or indirectly involved will be discussed in more detail. Surfactants and respiration In connection with the 1979 World Congress of Obstetrics and Gynaecology in Tokyo, Fujiwara demonstrated for the first time to an international group the dramatic effect of instillation of a surfactant in infants with respiratory distress. As is so often the case, the wide application has proven more complicated than expected and this is still indeed a frontline in perinatal medicine. A more recent approach to the treatment of severe pulmonary insufficiency is liquid ventilation, reported in 1990 by Greenspan and colleagues [l]. Correspondence to: GGsta Rooth, Department of Pediatrics, University of Uppsala, t)fre Slottsgatan 14 C, S-75 310 Uppsala, Sweden.
0378-3782/92/%05.00 0 1992 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland
22
Erytbropoietin Erythropoietin was a major subject of study at the Donner Laboratory of the Lawrence Berkeley Laboratories when the author worked there in 1963 and 1964. Their interest has been maintained and is now becoming most rewarding as important clinical applications are revealed. In 1985 Teramo and coworkers first observed that erythropoietin could be an indicator of fetal hypoxemia, a completely new approach to monitoring this condition [2]. Erythropoietin has also found an application in obstetrics. Thanks to gene technique, this substance is now commercially available and Danko et al. have shown that it can be used to advantage in post delivery anemia [3]. Cordocentesis and fetal interventions It was a major breakthrough when Saling initiated fetal scalp sampling. Today, we can obtain fetal blood before delivery, thanks to cordocentesis, i.e., the puncturing of the umbilical cord. This is, of course, a superior way of assessing fetal anemia and thrombocytopenia. The technique also allows direct chromosomal preparation of a placental biopsy taken simultaneously and can often provide a fetal karyotype the same day. Sothill feels that today cordocentesis could also be an alternative to fetal scalp sampling [4]. For the future he envisages treatment of severe inherited disease by gene therapy. Crossing the border into the unknown he hopes that the study of fetal endocrinology by cordocentesis may improve our understanding of the fetal role in the initiation of labor. Using endoscopy fetal surgery is gaining ground. The most important procedure as yet is the percutaneous catheter insertion to bypass a blockage. Computer assisted decision support Lilford edited a book in 1990 that gives an excellent review of the use of computer technique in obstetrics [5]. For instance, he mentions how computer-stored hospital records may be used for randomized controlled clinical studies. For years we saw several centers analyzing fetal heart rate patterns with computers, but the practical use was limited. In 1989, Dawes et al., were one of the first groups that really made computer assisted analysis of fetal heart rate patterns useful [6]. Their program is now available commercially. Lilford considers the computer assisted decision making of special importance in the future. It enables physicians and/or nurses to use more formal ways of dealing with severe problems than with what is usually called the intuitive approach. It also allows delegation of responsibilities without reducing competence in the decision making. Take the problem of fluid administration of a newborn premature infant. For a long time, Sedin, Hammarlund and coworkers have been studying transepidermal water loss, a complex function of gestational age and postnatal age, among other factors. To compensate, electrolytes and, usually, nutrients must be added to the water. Storing tables in the computer, Sedin et al. have elaborated a program thanks to which a neonatal nurse can initiate appropriate fluid therapy as soon as the infant is in the incubator [7]. The program calls for a
23
check within 1 h by a senior doctor and of course allows him to make whatever changes he deems advisable. Asphyxia, oxygen, hypoxia and oxygen toxicity Asphyxia of the newborn infant is and will remain a major problem in perinatal medicine. Without early and adequate treatment that offers the infant a chance for a successful life, death or debility will ensue. The clinical situation of asphyxia is well known but the biochemical background needs some clarification. It implies oxygen levels so low that the tissue requirements are insufficient, inter alia leading to a metabolic acidosis. However, at first, as soon as the fetal gas exchange is reduced, there is a respiratory acidosis, i.e., increased Pco*. With progression of the metabolic acidosis, the bicarbonate concentration is lowered. Thereby carbon dioxide is produced and Pco2 increases further. It is therefore of primary importance to initiate ventilation immediately after birth in order to decrease PCO, and to increase pH. At the same time, oxygen will be absorbed and the metabolic acidosis will gradually disappear. With near infrared spectroscopy, cot-side information may be obtained about cerebral oxygen saturation and hemodynamics, and with magnetic resonance spectroscopy not only intracellular pH but ATP and other phospho-compounds important for the brain metabolism may be studied. Monitoring of glucose with near infrared spectroscopy and a detailed study of amino acids and enzymes in the brain with magnetic resonance spectroscopy is soon to be available. Gradually, evidence has been brought forward that the greatest harm of hypoxia comes during the reoxygenation and not during the anoxic period. Three different mechanisms resulting from lack of oxygen are at present considered detrimental to the function of the cell. First, as mentioned, acidosis, second, free radicals and third, excitatory amino acids. Free radicals are molecules or atoms with an unpaired electron. These substances usually only exist for microseconds and are very active. As so often occurs in biology they are both good and bad: good, when produced in the macrophage and assist in the killing off of invading bacteria; bad, when they destroy vital cellular membranes. The two important free radicals in this connection are the superoxide radical 0; and the hydroxyl radical OH*, both being formed in the reactions hypoxanthinexanthine-urate. Hypoxanthine can either be recovered via inosine-5-phosphate or further metabolized to xanthine and uric acid. However, all these three reactions require oxygen, and hypoxanthine is therefore the final degradation product during hypoxia. As increased amounts of hypoxanthine are produced during hypoxia and it readily diffuses out of the cells it is probably the best marker for tissue hypoxia. Although it can be readily measured in any research unit, it has so far not been possible to convince the industry to produce a bedside method. The working hypothesis at present is that free radicals destroy the cellular membranes in the lungs, brain, retina or intestine of the premature infants, thus at least partly explaining the pathogenesis of some of the main diseases of prematurity. Experimental studies have shown that the combination of hypoxanthine and high oxygen concentrations is particularly harmful [8]. The generation of free radicals is
24
a function of the multiplication of the oxygen concentration with that of hypoxanthine. During resuscitation of the newborn this is exactly what is being done clinically and several textbooks stress that 100% oxygen should be used. It would not be surprising if a doctor in the United States could be sued because resuscitation was performed with equal parts of air and oxygen. The premature infant might get an iatrogenic disease if 100% oxygen was given because the physician considers this correct, but it would be a legalogenic disease if it were done to prevent a lawsuit. In fact, increased oxygen concentrations are not needed at all. During fetal life the activity in the electron chain is three times as high as a week after birth. Thus the cells will get the amount of oxygen they need even at a low pressure and the production of free radicals is kept at a minimum. In 1957 we published a report [9] on 12 premature infants kept in 15% oxygen until 40 weeks of gestation, without any untoward complications and in 1986 MacMahon et al. did the same in some very low birthweight infants in order to reduce the risk of retinopathy of prematurity [lo]. There is also protection from free radicals by other means than reducing the oxygen concentration: scavengers (e.g., dimethyl sulfoxide), antioxidants, (e.g., vitamin A, C and E) and antioxienzymes, the best known being superoxide dismutase and glutathione peroxidase. Furthermore, xanthine oxidase may be blocked by allopurinol, which is excellent in cases of gout, but not properly studied in the connection of tissue hypoxia. The third mechanism by which at least brain cells may be damaged is the so-called excitatory amino acids, as they increase dramatically in the brain during hypoxia. This is a term used mainly for glutamic and aspartatic acid. By over-exciting neurons, they injure them. In experimental studies Kjellmer et al. have demonstrated a beneficial effect of kynurenic acid, which is a non-specific antagonist [ 111. Further therapeutic possibilities are being discovered. As a result of the cellular injury the 10 OOO-fold concentration gradient between the calcium ion concentration in the interstitium and in the cytosol is greatly reduced. In adult experimental animals it was found that calcium antagonists were beneficial [ 121. Non-surgical abortion and sterilization
Both non-surgical abortion and sterilization have become extremely important realistic possibilities. The best known and most tested abortifacient is a progesterone blocker called RU 486. In France a 96% efficacy rate has been shown since the approval of the drug in 1988 and about 25% of the women in France who seek abortion use this technique. Using two insertions of intrauterine quinacrine pellets in over 10 000 cases of nonsurgical female sterilization, Kessel et al. have, over several years, found a failure rate of 3-5%. An addition of a 50-mg pellet of an antiprostaglandin seems to lower the failure rate [ 131. The cost for the drug and the inserter is only US $1. Perinatal problems in developing countries
Outside of the scientific advances lies a vast territory,
infinitely
larger and un-
25
fathomable in its complexity and which, by its dimension and poverty, defies most attempts for improvement in perinatal medicine. Few frontiers are more difficult to move than those between the rich and the poor, even when, as far too often is seen, the poor live in a rich country. It is helpful to look first at the ethical problems. As physicians responsible for a specific patient, we follow the Geneva Convention of 1949, ‘The health of my patient will be my first consideration.’ The Hippocratic oath, for long a medical guide, states: ‘The regimen I adopt shall be for the benefit of the patients according to my ability and judgment and not for their hurt or other wrong.’ Dealing with the problems of many individuals at the same time the latter oath has different consequences than the Geneva Convention. A prerequisite when dealing with large numbers of patients is the approach of catastrophe medicine, i.e., to sort out those with the best prognosis first and to treat them, leaving the severely wounded until resources allow them to be adequately cared for. Assume that some, as always limited, medical and other humanitarian assistance will be brought into an area where AIDS and malnutrition are both prevalent. The resources should then be used for mothers and children without AIDS and not starved beyond salvation. We must help the strongest to become healthy; otherwise there will be no one there to cultivate the land and tend the cattle, no one to build houses or work to bring revenue into the community. There are too many ants in the ant hill, to use a well known saying. Even China with its rigid birth control has failed to contain the population at 1000 millions. Already and worse to come, we are faced with incalculable numbers of sick, starving women and children. How can we expect such sick mothers, pregnant too young, to produce healthy strong infants who should improve the lot of their community? We simply must limit the number of births. Many women certainly try this the hard way - it is estimated that between 40 and 60 million abortions take place around the world annually. The goal of the Safe Motherhood Initiative for the year 2000 is to reduce maternal mortality by 50%. It sounds simplistic, but the safest way of accomplishing this is to reduce the pregnancies by half. We must all, wherever we work, actively support the recent International Federation of Gynecology and Obstetrics (FIGO) resolution stating that the knowledge as regards family planning and maternal and child health care is already available and that it is a question of local willpower more than of economic ease and scientific and technical novelties for this to improve. We are in many parts of the world faced with the problems expressed by Professor Harrison in Nigeria ‘African women want to have as many children as possible because it makes sense to do so under the conditions in which most of our people live’. Add to this two other factors: in some societies the men insist that their women should produce a child each year so that everyone can see that they are still men; in others, parents feel their families are incomplete without a son. Having only daughters, they feel compelled to beget more children. With the predicted pop&+ tion increase in 2025, at least 18 countries will have a population of more than 100 million; mega cities will contain 20 million. How can problems of air, water and food, not to speak of sewage, be solved for such masses? How can, as predicted, more than 100 million live along the Nile in Egypt?
26
References 1 Greenspan, J.S., Wolfson, M.R., Rubenstein, SD. and Shaffer T. (1990): Liquid ventilation of human preterm neonates. J. Pediatr., 177, 106-l 11. 2 Teramo, K.A., Widness, J.A., Clemonds, G.K., et al. (1987): Amniotic fluid erythropoietin correlates with umbilical plasma erythropoietin in normal and abnormal pregnancy. Obstet. Gynecol., 69, 710-716. 3 Danko, J., Huch, R. and Huch, A. (1990): Epoetin alfa for treatment of postpartum anaemia. Lancet, 1, 737-738. Sothill, P.W. (1989): Cordocentesis: Role in Assessment of Fetal Condition. Clin. Perinatol., 16, 755-770. Lilford, R.J. Bailibre’s Clinical Obstetrics and Gynaecology, Vol. 4, No. 4. Dawes, G.S., Houghton, C.R.S., Redman, C.W.G. and Visser, G.H. A. ( 1982): Pattern of the normal human fetal heart rate. Br. J. Obstet. Gynaecol., 89, 276-284. Sedin, G., Groth, T., Hammarlund, K. and Seidel, A. (1990): A knowledge based adviser for fluid therapy in the neonatal period. In: Computers and Perinatal Medicine, pp. 55-63. Editors: K. Maedel et al. Elsevier Science Publishers, Amsterdam. 8 Saugstad, O.D., Hallman, M., Abraham, J. (1984): Plasma hypoxanthine levels in newborn infants: A specific indicator of hypoxia. Pediatr. Res., 18, 501. 9 Sjiistedt, S. and Rooth, G. (1957): Low oxygen tension in the management of newborn infants. Arch. Dis. Child., 32, 397-400. ,lO MacMahon, I., Fleming, P.J., Speidel, B.I. and Dunn, P.M. (1986): Retinopathy of prematurity. Br. J. Obstet. Gynaecol., 93, 361-363. 11 Kjellmer, I. (1991): Etiology and pathophysiology of postasphyxial brain damage. Int. J. Tech. Assess Health Care, 7 Suppl. 1, 106-109. 12 Siesjo, B.K. (1981): Cell damage in the brain: a speculative synthesis. J. Cereb. Blood Flow Metab., 1, 155-185. 13 Kessel, E., Zipper, J. and Mumford, S. (1990): The Quinacrine Pellet Method for Nonsurgical Female Sterilization: A Collection of Background Material. Center for Research on Population and Security, Research Triangle Park, NC.
