Recent developments in neonatal-perinatal medicine Perinatology by definition covers the period just before and after childbirth, but in practice it starts at the time of conception. Thus, the subspecialty involves two individuals, an obstetrician and a pediatrician (neonatologist). Both must have full knowledge and understanding of fetal and neonatal physiopathology. This obvious combination of skills and interests has become operational only in the last 5 years. In fact, the American Academy of Pediatrics gave official endorsement to the subspecialty of neonatal-perinatal medicine only in November 1975, when the first certifying examination was organized. The great impact that neonatal intensive care had on neonatal mortality' triggered interest among obstetricians to provide a similar type of intensive care for the fetus. The result of this common effort should be a further reduction in perinatal mortality and morbidity approaching the ideal basic level. As with any developing specialty, much progress has been made in the past few years and a better, though still fragmentary, understanding of perinatal physiopathology has ensued. Technical developments have followed the same trend, thereby permitting better recognition and treatment of risk situations. Perinatal care and its recent developments can be divided into four periods - the first 20 weeks of gestation, the antepartum period, the intrapartum period and the neonatal period. It is estimated that 10 to 15% of congenital or hereditary defects can now be diagnosed antenatally' by examination of amniotic fluid. The hazards of transabdominal amniocentesis for the fetus and the mother are extremely small.3 Major indications for amniocentesis are detection of chromosomal anomalies and inherited biochemical disorders, and advanced maternal age. A continuously growing list of over 60
hereditary metabolic diseases can now be diagnosed in utero.4 Although still in an experimental stage, fetoscopy is a promising new development.5 This delicate technique allows sampling of fetal blood between 18 and 20 weeks of gestation for the diagnosis of hemoglobinopathies and for the detection of anatomic anomalies by direct visualization of the fetus. Ultrasound helps in localization of the placenta, exact assessment of gestational age (by measurement of the hiparietal diameter), diagnosis of multiple pregnancy and detection of anencephaly. In the antepartum period fetal growth, degree of maturity and general well-being can be determined by ultrasound, measurement of urinary estriols, the oxytocin challenge test and amniocentesis. Retarded intrauterine growth can now be easily diagnosed and early delivery contemplated when the fetus is in jeopardy.6 For the same reasons the management of pregnancy in diabetic women has become more accurate. Fetal lung maturity, as reflected in the production of surfactant and its presence in the amniotic fluid, is an excellent risk predictor for the respiratory distress syndrome.7 This is particularly important since administration of betamethasone (between 28 and 33 weeks of gestation) to the mother is helpful in accelerating fetal lung maturity, provided it is given 24 hours before delivery.8 However, the safety of this potent steroid for the fetus has not yet been confirmed and further studies are needed before its general use can be recommended.9 Monitoring during labour of fetal heart rate, pH and uterine contractions has practically eliminated asphyxia as a cause of perinatal mortality and has lessened neonatal morbidity. The price of this continuous monitoring of fetal well-being seems to be an increased
number of cesarean sections. Precise and more intelligent interpretation of the information obtained by fetal monitoring is still to come. The decreased incidence of asphyxia in the neonatal period has resulted in increased survival of infants weighing less than 1500 g. Decreased perinatal insult in terms of asphyxia, acidosis and cold stress, better resuscitative measures and immediate initiation of therapy, together with acceleration of lung maturity by antenatal injection of betamethasone, have greatly decreased the incidence of the respiratory distress syndrome. Also, in terms of active therapy for this condition, a breakthrough has been made in the last 3 years with the early use of continuous distending airway pressure.'0 With this technique the severity of the condition can be ameliorated, allowing better tissue oxygenation and faster lung recovery. More experience with ventilators and better equipment have also been important factors in the decreased mortality from the respiratory distress syndrome. In the future this condition should be almost completely eliminated as a cause of neonatal death. A challenge for neonatologists is the care of the infant weighing les. than 1500 g. Remarkable progress has been made in the last 3 years in recognizing and treating the specific problems of the very premature infant. Our experience with such babies at present is as follows: survival rate for infants 750 to 1000 g in weight, 60%; for those 1000 to 1250 g, 90%; and for those 1250 to 1500 g, 95%. We believe that the use of total intravenous alimentation is one of the most important factors in the successful management of these small infants. Apnea of prematurity and patent ductus arteriosus are frequently present at the same time, although not necessarily interrelated. The use of xanthines" and continuous distending
CMA JOURNAL/JULY 23, 1977/VOL. 117 109
Catapres®
clonidine hydrochloride
I .r
PRESCRIBING INFORMATION .Wen 2-(2,6-dlchlorophenylamino)-2-imidazcline hydrochbride. IuudIcatIsns Catapres hasbeen usedsuccessfullytotreathypertensionofallgrades of severity. Coabulndloatlmis There are no known absolute contraindications to the use of Catapres. Wmluigs B Gatapres therapy is discontinued for any reason, withdrawal should be done gradually over several days rather than abruptly. There have been rare instances of rebound hypertensive crises following sudden discontinuationofhrghdosesofthedrug. Thiscanbeeffectivelycontrolled by reinstituting Catapres at the previous dosage level; however if more rapid control is necessary, intravenous infusions of atpha adrener0c blocking agents such as intravenous phentolemine (5-10mg doses at 5 minute intervals up to a total of 30 mg) are effective in reducing the blood pressure. PrecautIons Patients with a known history of depression should be carefully supervised whls under treatment with Catapres, as there have been occasionalreportsoffurtherdepressiveepisodesoccurringinsuch patients. As an abruptwithdrawal of Catapres is followed in rare instances by an escesa of circulating catecholamines, caution should be exercised in the concomitant use of drugs which affect the metabolism or the tissue uptake of these amines (MAO inhibltors and tricyclic antidepressants respectively). A few instances of a condition resembing Raynauds phenomenon have been reported. Caution shouhi therefore be deserved if pabents with Raynaud's disease or thrornboangiitis obliterans are lobe treated with Catapres. Catapres has a mucous membrane drying effect on the eyes. On rare occasions this has led to comeal ulceration. As with any drug excreted primarily in the urine, smaller doses of Catapres are often effective in tr.ating patients with a degree of renal feilure. The use of Catapres during the first trimesterof pregnancyis sub(ectto the normal precautions surrounding the use of any drug. Animal tests hey shown no tividence of foetat abnormality, though there was some decreased fertitty. Adverse effects The most commonly encountered side effects are initial sedabon and dry mouth, However these effects are seldom severe and tend to be dose relafed and transient. There are occasional reports of fluid retention and weighi gain daring the initisi stages of treatment with Cataprex. This side effects ususily transient, hot the addition ofa diuretic will correct any tendency to fluid retention in these cases. Other occasional drug-related side effects which have been noted in Hterafureincludadizziness, headache, dryness, itchingorburningof the eyes, rarely comesl ulceration, noctumal unrest, nausea, euphoria, constipation, impotence (rarely), and agitationonwithdrawalof therapy. Facial pallor has occasionally been noted at high dosage levels. No toxlc reactions have been deserved on investigating blood status, renal function and fiver function. Long-term treatment has shown no adverse effect on blood urea nitrogen lsvels, and in patients with prwexisting rensi damage there is no suggestion of further impairment of the renal blood flow despife a fell in arterisi blood pressure. Dosage Initially 0.05-0.1 mg four times daily. This dosage may be increased every few days until satisfactory control is achieved. When usedalone the final dosage usually ranges between 0.2 and 1.2mg daily. The last dose of the day should begiven immediately before retiring to ensure blood pressure control during sleep. Catapres used with a diuretic Catapres has been used successfully together with chlorthatidone, furosemide and the thiazide diuretica. Lower doses of Catapres or the diuretic may be used to achieve the same degree ot blood pressure control whenever a diuretic is added to the Catapres regimen or vice versa. In these circumstances, most rreld-lo-inoderete hyperrenaivex can be controlled using only 0.3-0.6 mg of Catapres daily in divided doses. AvellabINfly 1. 0.1 mg Tablet:Awhite, single-scoredtablet, impressedwiththe motif on one ade and the Boehringer Ingelheim symbol on the reverse. Bottles of 100 and 500 tablets. 2.0.2mg Tab/eLAn orange, single-scored tablet, impressed with the motif on one side and the Boehringer Ingetheim symbolon the reverse. Bottles of 50 and Sootablsts. Comblpres is available ass pink sugar-coated tabletoontaining 0.1 mg Catapres and 15 mg chlorthatidone. Suppiied in bottles of 50 and 500 tablets. For further preacriblng informahon, consult the Catapres Product Monograph or your Boehringer Ingelheim representative.
(j'\ Boehrlng.r Ingeiheim (Canada) Ltd.
2121 TrensCanadsHlghway, Dorval, P.Q, I*P 1J3
B-251-77
111111
airway pressure12 has greatly decreased the severity and frequency of apnea due to prematurity. Prostaglandin inhibitors13 and continuous distending airway pressure14 are two new therapeutic tools in the management of cardiorespiratory failure from patent ductus arteriosus. Two recent challenges for the neonatologist are the sudden increase in the incidence of necrotizing enterocolitis11 and group B .G-hemolytic streptococcal infection.16 Both conditions are not always successfully treated and the mortality and morbidity rates are quite high. Perinatal intensive care has proved effective in reducing perinatal mortality. Our experience indicates that morbidity follows the same pattern. This, however, remains to be proven on a larger scale. Regionalization of pennatal care is already developing rapidly across North America. Problems of family separation, parental psychologic trauma and continuity of care are far from being resolved. Public and professional scepticism and private interest are still to be overcome, but the data support such an effort.17 Of particular concern to perinatologists is the poor prognosis for infants weighing less than 1500 g who survive mechanical ventilation.18 This concern has given rise to profound ethical debate on how aggressive the therapy for extremely small infants should be. Neonatologists, like other physicians, theologians and the interested public, are struggling with the issue. It is hoped that with better perinatal and neonatal care, including the early recognition and transfer of women with high-risk pregnancies to specialized centres, the eventual prevention of prematurity and the respiratory distress syndrome, and the elimination of fetal and neonatal asphyxia, a notable reduction in the number of infants of small size requiring assisted ventilation will follow. Perinatology, in its short life as a unified specialty, has already made much progress. Fortunately the success of perinatology has been paralleled by a renewed interest in the problem of the risk to bonding necessitated by the technical advances and regionalization. Perinatologists have been pioneers in developing methods for enhancing appropriate parental attachment and integrating parents into the intensive care centre.19 With so much emphasis now being placed on prevention rather than correction, perhaps an even larger avenue for further progress in fetal, maternal and neonatal welfare will be opened. APOSTOLOS N. PAPAGEORGIOU, MD, FRCP[C] Assistant professor of pediatrics, and obstetrics and gynecology McGill University Montreal, PQ
112 CMA JOURNAL/JULY 23, 1977/VOL. 117
References 1. USHER R: Clinical implications of perinatal mortality statistics. Clin Obstet Gynecol 14: 885, 1971 2. MILUNSEY A: Prenatal diagnosis of genetic abnormalities. Clin Perinatol 1: 25, 1974 3. SIMPSON NE, DALLAIRE L, MILLER JR, et al: Prenatal diagnosis of genetic disease in Canada: report of a coliaborative study. Can Med Assoc 1 115: 739, 1976 4. MILUNSKY A: Prenatal diagnosis of genetic disorders. N Engi J Med 295: 377, 1976 5. Hoesms JC, MAHONEY MJ: In utero diagnosis of hemoglobinopathies. Technic for obtaining fetal blood. N Engi I Med 290:
1065, 1974
6. CAMPBELL 5: The assessment of fetal development by diagnostic ultrasound. Clin Pen-
nato! 1: 507, 1974
7. GLUCK L, KULOVICH MV, BORER RC JR,
et al: Diagnosis of the respiratory distress syndrome by amniocentesis. Am I Obstel Gynecol 109: 440, 1971
8. LIGGINs GC, HowlE RN: A controlled trial of antepartum glucocorticoid treatment for prevention of respiratory distress syndrome
in premature infants. Pediatrics 50: 515, 1972
9. GLUCK L: Administration of corticosteroids to induce maturation of fetal lung. Am J Dis
Child 130: 976, 1976
10. GERARD P, Fox WW, OUTERBRIDGE EW, et al: Early versus late introduction of continuous negative pressure in the management of the idiopathic
respiratory
distress syndrome.
.1
Pedjatr 87: 591, 1975 11. SHANNON DC, GOTAY F, STEIN IM, et al: Prevention of apnea and bradycardia in lowbirthweight infants. Pediatrics 55: 589, 1975 12. KATYWINKEL J, NEARMAN HS, FANAROFF AA, et al: Apnea of prematurity. Comparative therapeutic effects of cutaneous stimulation and nasal continuous positive airway pressure.
I Pediatr 86: 588, 1975
13. FRIEDMAN WF, HIRSCHKLAU MJ, PRINTZ MP, et al: Pharmacologic closure of patent ductus arteriosus in the premature infant. N Engi .1
Med 295: 526, 1976
14. PAPAGEORGIOU AN, DESORANGES MF: Continuous distending alrway pressure in the management of cardiorespiratory failure from
PDA (abstr). Ann R Coil Physicians Surg Can 10: 91, 1976
15. TOULOUKIAN RM: Neonatal necrotizing en-
terocolitis - an up-dat9 on etiology, diagnosis, and treatment. Surg Clin North Am 56: 281, 1976
16. FEIGIN RD: The perinatal group B streptococcal problem: more questions than answers (E). N Engi I Med 294: 106, 1976 17. PAPAGEORGIOU AN, MASSON M, SHATE R, et al: Specialized perinatal care: impact on perinatal mortality. Can Med Assoc 1 116: 506, 1977 18. FITZHARDINGE PM, PAPE K, ARSTIKAITIS M, et al: Mechanical ventilation of infants of less than 1,501 gin. birth weight - health, growth and neurologic sequelse. I Pediatr
88: 531, 1976
19. KLAUS MH, JERAULD R, KJIEGER NC, et al:
Maternal attachment: importance of the first post-partum days. N Engl I Med 286: 460, 1972
hereditary metabolic diseases can now be diagnosed in utero.4 Although still in an experimental stage, fetoscopy is a promising new development.5 This delicate technique allows sampling of fetal blood between 18 and 20 weeks of gestation for the diagnosis of hemoglobinopathies and for the detection of anatomic anomalies by direct visualization of the fetus. Ultrasound helps in localization of the placenta, exact assessment of gestational age (by measurement of the hiparietal diameter), diagnosis of multiple pregnancy and detection of anencephaly. In the antepartum period fetal growth, degree of maturity and general well-being can be determined by ultrasound, measurement of urinary estriols, the oxytocin challenge test and amniocentesis. Retarded intrauterine growth can now be easily diagnosed and early delivery contemplated when the fetus is in jeopardy.6 For the same reasons the management of pregnancy in diabetic women has become more accurate. Fetal lung maturity, as reflected in the production of surfactant and its presence in the amniotic fluid, is an excellent risk predictor for the respiratory distress syndrome.7 This is particularly important since administration of betamethasone (between 28 and 33 weeks of gestation) to the mother is helpful in accelerating fetal lung maturity, provided it is given 24 hours before delivery.8 However, the safety of this potent steroid for the fetus has not yet been confirmed and further studies are needed before its general use can be recommended.9 Monitoring during labour of fetal heart rate, pH and uterine contractions has practically eliminated asphyxia as a cause of perinatal mortality and has lessened neonatal morbidity. The price of this continuous monitoring of fetal well-being seems to be an increased
number of cesarean sections. Precise and more intelligent interpretation of the information obtained by fetal monitoring is still to come. The decreased incidence of asphyxia in the neonatal period has resulted in increased survival of infants weighing less than 1500 g. Decreased perinatal insult in terms of asphyxia, acidosis and cold stress, better resuscitative measures and immediate initiation of therapy, together with acceleration of lung maturity by antenatal injection of betamethasone, have greatly decreased the incidence of the respiratory distress syndrome. Also, in terms of active therapy for this condition, a breakthrough has been made in the last 3 years with the early use of continuous distending airway pressure.'0 With this technique the severity of the condition can be ameliorated, allowing better tissue oxygenation and faster lung recovery. More experience with ventilators and better equipment have also been important factors in the decreased mortality from the respiratory distress syndrome. In the future this condition should be almost completely eliminated as a cause of neonatal death. A challenge for neonatologists is the care of the infant weighing les. than 1500 g. Remarkable progress has been made in the last 3 years in recognizing and treating the specific problems of the very premature infant. Our experience with such babies at present is as follows: survival rate for infants 750 to 1000 g in weight, 60%; for those 1000 to 1250 g, 90%; and for those 1250 to 1500 g, 95%. We believe that the use of total intravenous alimentation is one of the most important factors in the successful management of these small infants. Apnea of prematurity and patent ductus arteriosus are frequently present at the same time, although not necessarily interrelated. The use of xanthines" and continuous distending
CMA JOURNAL/JULY 23, 1977/VOL. 117 109
Catapres®
clonidine hydrochloride
I .r
PRESCRIBING INFORMATION .Wen 2-(2,6-dlchlorophenylamino)-2-imidazcline hydrochbride. IuudIcatIsns Catapres hasbeen usedsuccessfullytotreathypertensionofallgrades of severity. Coabulndloatlmis There are no known absolute contraindications to the use of Catapres. Wmluigs B Gatapres therapy is discontinued for any reason, withdrawal should be done gradually over several days rather than abruptly. There have been rare instances of rebound hypertensive crises following sudden discontinuationofhrghdosesofthedrug. Thiscanbeeffectivelycontrolled by reinstituting Catapres at the previous dosage level; however if more rapid control is necessary, intravenous infusions of atpha adrener0c blocking agents such as intravenous phentolemine (5-10mg doses at 5 minute intervals up to a total of 30 mg) are effective in reducing the blood pressure. PrecautIons Patients with a known history of depression should be carefully supervised whls under treatment with Catapres, as there have been occasionalreportsoffurtherdepressiveepisodesoccurringinsuch patients. As an abruptwithdrawal of Catapres is followed in rare instances by an escesa of circulating catecholamines, caution should be exercised in the concomitant use of drugs which affect the metabolism or the tissue uptake of these amines (MAO inhibltors and tricyclic antidepressants respectively). A few instances of a condition resembing Raynauds phenomenon have been reported. Caution shouhi therefore be deserved if pabents with Raynaud's disease or thrornboangiitis obliterans are lobe treated with Catapres. Catapres has a mucous membrane drying effect on the eyes. On rare occasions this has led to comeal ulceration. As with any drug excreted primarily in the urine, smaller doses of Catapres are often effective in tr.ating patients with a degree of renal feilure. The use of Catapres during the first trimesterof pregnancyis sub(ectto the normal precautions surrounding the use of any drug. Animal tests hey shown no tividence of foetat abnormality, though there was some decreased fertitty. Adverse effects The most commonly encountered side effects are initial sedabon and dry mouth, However these effects are seldom severe and tend to be dose relafed and transient. There are occasional reports of fluid retention and weighi gain daring the initisi stages of treatment with Cataprex. This side effects ususily transient, hot the addition ofa diuretic will correct any tendency to fluid retention in these cases. Other occasional drug-related side effects which have been noted in Hterafureincludadizziness, headache, dryness, itchingorburningof the eyes, rarely comesl ulceration, noctumal unrest, nausea, euphoria, constipation, impotence (rarely), and agitationonwithdrawalof therapy. Facial pallor has occasionally been noted at high dosage levels. No toxlc reactions have been deserved on investigating blood status, renal function and fiver function. Long-term treatment has shown no adverse effect on blood urea nitrogen lsvels, and in patients with prwexisting rensi damage there is no suggestion of further impairment of the renal blood flow despife a fell in arterisi blood pressure. Dosage Initially 0.05-0.1 mg four times daily. This dosage may be increased every few days until satisfactory control is achieved. When usedalone the final dosage usually ranges between 0.2 and 1.2mg daily. The last dose of the day should begiven immediately before retiring to ensure blood pressure control during sleep. Catapres used with a diuretic Catapres has been used successfully together with chlorthatidone, furosemide and the thiazide diuretica. Lower doses of Catapres or the diuretic may be used to achieve the same degree ot blood pressure control whenever a diuretic is added to the Catapres regimen or vice versa. In these circumstances, most rreld-lo-inoderete hyperrenaivex can be controlled using only 0.3-0.6 mg of Catapres daily in divided doses. AvellabINfly 1. 0.1 mg Tablet:Awhite, single-scoredtablet, impressedwiththe motif on one ade and the Boehringer Ingelheim symbol on the reverse. Bottles of 100 and 500 tablets. 2.0.2mg Tab/eLAn orange, single-scored tablet, impressed with the motif on one side and the Boehringer Ingetheim symbolon the reverse. Bottles of 50 and Sootablsts. Comblpres is available ass pink sugar-coated tabletoontaining 0.1 mg Catapres and 15 mg chlorthatidone. Suppiied in bottles of 50 and 500 tablets. For further preacriblng informahon, consult the Catapres Product Monograph or your Boehringer Ingelheim representative.
(j'\ Boehrlng.r Ingeiheim (Canada) Ltd.
2121 TrensCanadsHlghway, Dorval, P.Q, I*P 1J3
B-251-77
111111
airway pressure12 has greatly decreased the severity and frequency of apnea due to prematurity. Prostaglandin inhibitors13 and continuous distending airway pressure14 are two new therapeutic tools in the management of cardiorespiratory failure from patent ductus arteriosus. Two recent challenges for the neonatologist are the sudden increase in the incidence of necrotizing enterocolitis11 and group B .G-hemolytic streptococcal infection.16 Both conditions are not always successfully treated and the mortality and morbidity rates are quite high. Perinatal intensive care has proved effective in reducing perinatal mortality. Our experience indicates that morbidity follows the same pattern. This, however, remains to be proven on a larger scale. Regionalization of pennatal care is already developing rapidly across North America. Problems of family separation, parental psychologic trauma and continuity of care are far from being resolved. Public and professional scepticism and private interest are still to be overcome, but the data support such an effort.17 Of particular concern to perinatologists is the poor prognosis for infants weighing less than 1500 g who survive mechanical ventilation.18 This concern has given rise to profound ethical debate on how aggressive the therapy for extremely small infants should be. Neonatologists, like other physicians, theologians and the interested public, are struggling with the issue. It is hoped that with better perinatal and neonatal care, including the early recognition and transfer of women with high-risk pregnancies to specialized centres, the eventual prevention of prematurity and the respiratory distress syndrome, and the elimination of fetal and neonatal asphyxia, a notable reduction in the number of infants of small size requiring assisted ventilation will follow. Perinatology, in its short life as a unified specialty, has already made much progress. Fortunately the success of perinatology has been paralleled by a renewed interest in the problem of the risk to bonding necessitated by the technical advances and regionalization. Perinatologists have been pioneers in developing methods for enhancing appropriate parental attachment and integrating parents into the intensive care centre.19 With so much emphasis now being placed on prevention rather than correction, perhaps an even larger avenue for further progress in fetal, maternal and neonatal welfare will be opened. APOSTOLOS N. PAPAGEORGIOU, MD, FRCP[C] Assistant professor of pediatrics, and obstetrics and gynecology McGill University Montreal, PQ
112 CMA JOURNAL/JULY 23, 1977/VOL. 117
References 1. USHER R: Clinical implications of perinatal mortality statistics. Clin Obstet Gynecol 14: 885, 1971 2. MILUNSEY A: Prenatal diagnosis of genetic abnormalities. Clin Perinatol 1: 25, 1974 3. SIMPSON NE, DALLAIRE L, MILLER JR, et al: Prenatal diagnosis of genetic disease in Canada: report of a coliaborative study. Can Med Assoc 1 115: 739, 1976 4. MILUNSKY A: Prenatal diagnosis of genetic disorders. N Engi J Med 295: 377, 1976 5. Hoesms JC, MAHONEY MJ: In utero diagnosis of hemoglobinopathies. Technic for obtaining fetal blood. N Engi I Med 290:
1065, 1974
6. CAMPBELL 5: The assessment of fetal development by diagnostic ultrasound. Clin Pen-
nato! 1: 507, 1974
7. GLUCK L, KULOVICH MV, BORER RC JR,
et al: Diagnosis of the respiratory distress syndrome by amniocentesis. Am I Obstel Gynecol 109: 440, 1971
8. LIGGINs GC, HowlE RN: A controlled trial of antepartum glucocorticoid treatment for prevention of respiratory distress syndrome
in premature infants. Pediatrics 50: 515, 1972
9. GLUCK L: Administration of corticosteroids to induce maturation of fetal lung. Am J Dis
Child 130: 976, 1976
10. GERARD P, Fox WW, OUTERBRIDGE EW, et al: Early versus late introduction of continuous negative pressure in the management of the idiopathic
respiratory
distress syndrome.
.1
Pedjatr 87: 591, 1975 11. SHANNON DC, GOTAY F, STEIN IM, et al: Prevention of apnea and bradycardia in lowbirthweight infants. Pediatrics 55: 589, 1975 12. KATYWINKEL J, NEARMAN HS, FANAROFF AA, et al: Apnea of prematurity. Comparative therapeutic effects of cutaneous stimulation and nasal continuous positive airway pressure.
I Pediatr 86: 588, 1975
13. FRIEDMAN WF, HIRSCHKLAU MJ, PRINTZ MP, et al: Pharmacologic closure of patent ductus arteriosus in the premature infant. N Engi .1
Med 295: 526, 1976
14. PAPAGEORGIOU AN, DESORANGES MF: Continuous distending alrway pressure in the management of cardiorespiratory failure from
PDA (abstr). Ann R Coil Physicians Surg Can 10: 91, 1976
15. TOULOUKIAN RM: Neonatal necrotizing en-
terocolitis - an up-dat9 on etiology, diagnosis, and treatment. Surg Clin North Am 56: 281, 1976
16. FEIGIN RD: The perinatal group B streptococcal problem: more questions than answers (E). N Engi I Med 294: 106, 1976 17. PAPAGEORGIOU AN, MASSON M, SHATE R, et al: Specialized perinatal care: impact on perinatal mortality. Can Med Assoc 1 116: 506, 1977 18. FITZHARDINGE PM, PAPE K, ARSTIKAITIS M, et al: Mechanical ventilation of infants of less than 1,501 gin. birth weight - health, growth and neurologic sequelse. I Pediatr
88: 531, 1976
19. KLAUS MH, JERAULD R, KJIEGER NC, et al:
Maternal attachment: importance of the first post-partum days. N Engl I Med 286: 460, 1972
