Acta Padiatr Suppl 382: 10-12. 1992
Management of extremely low-birth-weight infants Carlo Coccia, Marco Pezzani, Guido E Moro and Iolanda Minoli Depurlmenr of Perinalul Purhology. Proirinciul Marerniry Hospilul. Uni1:ersil.vof Milun. Milun. IIU!,~
Coccia C, Pezzani M, Moro GE, Minoli 1. Management of extremely low-birth-weight infants. Acta Prediatr 1992;Suppl 382: 10-12. Stockholm. ISSN 0803-5253 Better health care of women during pregnancy and delivery, improvement in neonatal intensive therapy and technology have led to a decrease in neonatal mortality and morbidity and to lower limits of birth weight and gestational age for survival. This paper refers to the management protocol used in the Department of Perinatal Pathology of the Provincial Maternity Hospital of Milan for extremely low-birth-weight (ELBW) infants (birth weight < 1000 g). In this hospital, all newborn infants presenting evidence of life, irrespective of birth weight and gestational age, are resuscitated and transferred to the Neonatal Intensive Care Unit (NICU) for clinical management. After the introduction of this protocol the mortality rate of ELBW infants dropped from 71.4% in 1977-78 to 48% in 1987-88. In a group of 72 ELBW infants with a mean birth weight of 850 g and a mean gestational age of 27 weeks, 80% presented a normal outcome, 12% presented a mild neurological impairment and 8% were affected by severe cerebral palsy at the age of two years. The intact survival of a newborn infant of 450 g at birth is also reported. G E Moro, Dii>isione di Patologin Perinatale, Istituto Ospedaliero Protlinciale p e r la M a t e r n i t a . V i a M . Melloni. 52, 20129 Milano, Italj’
We describe the management protocol used at the present time in our Neonatal Intensive Care Unit (NICU) in Milan for the extremely low-birth-weight (ELBW) infant (birth weight < 1000 g) and the outcome of a newborn with a birth weight of 450 g.
Management protocol of ELBW infants
prevent dehydration and to reduce the incidence of complications, such as necrotizing enterocolitis, cardiac failure and patent ductus arteriosus, which can be related to an excessive intake of fluid (I). Beginning with a total fluid intake of 60 ml/kg in the first day of life, we increase the fluid intake progressively in the first four days of life with a rate of 20 ml/kg/day and then use increments of 10 ml/kg/day to reach a maximum of 160-180 ml/kg/day between day 10 and 14. (5) Enteral feeding comprises subnutritional amounts of fresh human milk, administered from the second day of life, concomitantly with total parenteral nutrition. This minimal enteral feeding helps the physiological development of the gastrointestinal apparatus, stimulating the hormonal and enzymatic activities (2). Continuous nasoduodenal feeding avoids complications related to the introduction of food into the stomach and allows a precocious alimentation and an adequate caloric intake during the first days of life (3). (6) Early daily contact between mother and infant is encouraged for the psychophysical well-being of both.
( I ) Endotracheal intubation in the delivery room. As the first minutes of life are extremely important for survival and quality of life, endotracheal intubation is performed routinely in the delivery room, immediately after birth, in order to prevent alveolar collapse, excessive respiratory efforts, and metabolic and respiratory acidosis. (2) Early percutaneouscentral venous line placement. A percutaneous central venous catheter is inserted for parenteral nutrition and to reduce the frequency of stressful venipunctures. (3) Minimal handling and sterile procedures are essential to reduce the risk of neonatal infections. To avoid the stress of frequent manipulations, we concentrate several procedures together. When the baby is Results handled for blood samples, suctioning from the endotracheal tube, positioning of electrodes and baby clean- Following the introduction of this protocol, the moring are performed. Because of continuous transpyloric tality rate of the ELBW infants admitted to our NICU feeding, the infant is handled for enteral nutrition only decreased from 71.4%0in 1975-1978 to 48% in 1985every 2-3 days. 1988. Seventy-two ELBW infants (mean birth weight (4) Fluid intake is controlled accurately in order to 850 g and mean gestational age 27 weeks) admitted to
ACTA PRDIATR SUPPL 382 (19921
the NICU survived in the period 1985-1988. These babies were followed regularly with neurological evaluation during the first two years of life. Eighty percent presented a normal outcome, 12% mild neurological impairment and 8% were affected by severe cerebral Palsy (4).
Case report We recently reported the case of an infant with a birth weight of 450 g (5) and we can now summarize her clinical history and refer to her neurodevelopmental follow-up. Valentina L was born in the Provincial Maternity Hospital, Milan, on May 7, 1988, after 27 weeks gestation. She was the second child of a 37-year-old mother who had delivered a female child with a birth weight of 2190 g and a gestational age of 38 weeks four years previously. The maternal history revealed some cigarette smoking during pregnancy and ultrasonographic examinations had shown intrauterine growth retardation from the 22nd week of gestation. Owing to severe maternal eclampsia, the infant was delivered by cesarean section. Birth weight was 450 g, length 29.5 cm and head circumference 21 cm. Apgar score at 1 min was 1; consequently the infant was intubated with a nasotracheal tube (Portex No. 2) immediately after birth and ventilated with intermittent positive pressure ventilation and 100% oxygen. Apgar score at 5 min was 6. The infant was admitted to the NICU. A roentgenogram performed 4 h after birth showed a stage I1 respiratory distress syndrome and a right pneumothorax that resolved spontaneously in 36 h. The patient was mechanically ventilated continuously up to the 35th day of life. The maximum oxygen concentration (apart from 100% oxygen given at birth) was 80% for 16 h on the 26th day of life. A percutaneous central venous catheter was inserted for parenteral nutrition and on the second day of life an exchange transfusion was carried out through an umbilical venous catheter because of hyperbilirubinemia (9.5 mg/dl after 14 h of life). Several episodes of clinically asymptomatic hypoglycemia occurred in the first days of life in spite of high parenteral glucose intakes. On the second day of life, parenteral feeding was begun because of delayed passage of meconium and abdominal distension. A diagnosis of intestinal obstruction was confirmed by roentgenograms and, on the 10th day of life, surgery was performed. Intraoperative findings included a subatretic segment of distal ileum, just proximal to the ileocecal valve. Sparing the ileocecal valve and the terminal ileum, the atretic portion was removed and an end-to-end (onelayer) anastomosis was performed. Postoperatively, poor canalization with persistent abdominal distension and bile-stained fluid from the feeding tube were observed. Radiographic examination revealed a persist-
Munugemeni
of ELB W infunis
I1
ent intestinal obstruction and the abdomen was reexamined on the 23rd day of life. A stenosis with dilatation of the proximal ileal segment was evident at the level of the previous anastomosis and s o . a new resection, including the ileocecal valve, with an end-toend anastomosis between the ileum and the ascending colon, was performed. After the second operation, the baby had an uneventful recovery. On the 30th day of life enteral feeding was started with fresh mother’s milk. From the 49th day of life, the infant received fortified human milk from the bank until the 73rd day of life when artificial formula was started. The infant developed a retinopathy of prematurity at stage I that resolved spontaneously. During her stay in the NICU, all cranial scans performed were normal. When the infant was discharged at 5.5 months ofage, her weight was 2100 g, length 43.5 cm and head circumference 32 cm. Her clinical condition was satisfactory. Neurodei~elopmentdfollow-up The infant’s ultrasound brain scan and neurological state appeared normal at serial examinations during the first trimester of life. A small reduction in fine coordination and balance was detected in the first 9 months of life. These mild neurological signs disappeared at 12 months. Independent walking was reached at 21 months of age (18 months corrected age) and her neurological assessment appeared normal at the age of 22 months (19 months corrected age). Thus the mild neurological deficit detected during the first three trimesters may be considered as a transitory developmental delay in some neurological functions. At the last neurodevelopmental assessment at the chronological age of 46 months, the child presented a normal neurological state and developmental progress. The patient is a tiny child (weight 10070 g and length 91 cm at the age of 3 years and 1 1 months), uninhibited and interested in people and the environment. She has a good attitude to communication and social activity. She is able to concentrate her attention during spontaneous play and developmental tests. N o behavioural or autonomic problems were observed in the first years of life. She recently showed good adaptation to kindergarten, without any difficulty. Her general developmental quotient using the Griffith’s scale was 81 at 18 months corrected age; since the normal range of this test is 76 (borderline 73-79), her development could be considered normal. In subsequent developmental evaluations at 37 and 46 months of chronological age, general developmental quotients at the Griffith’s extension scale were 75.8% and 78%, respectively (borderline). In both cases, the general developmental quotient could still be considered within the normal range if score was related to corrected age. The child presented difficulties mostly in visuomotor and fine manipulation skills. In fact, in the “hand
12
C Coccia el a/.
ACTA PEDIATR SUPPL 382 (1992)
and eye coordination subscale” the subquotient was 64.8% at 37 months and 65.8% at 46 months of age. In the “hearing and speech subscale”, the subquotient was 75.8% at 37 months and 65.6% at 46 months of age. Speech was more delayed than language, and the child was able to produce short sentences of four words at 37 months of age. Also, in the “practical reasoning subscale”, in which language is widely requested, the score was below the range of normality. In conclusion, the child now presents a mild psychomotor delay at the borderline range, but an improvement in development with improvement of language and speech is expected.
Neonatologists will have to cope with some aspects of neonatology which are not yet completely clarified and standardized, such as handling, growth, nutritional status assessment and long-term neurodevelopmental follow-up of ELBW infants.
Conclusions
References
Valentina is not the only infant with a birth weight less than 500 g who survived with a normal neurodevelopmental outcome. Other cases have been reported recently: Heiko, born in Ludwigshafen/Rhein (Germany) with a birth weight of 460 g (H Karte, personal communication); Ramona, born in Bern (Switzerland) with a birth weight of 390 g (see p. 7); Monica, born in New Orleans (USA) with a birth weight of 380 g (6, see also p. 13); and the smallest infant, a female of 280 g, born in Maywood (USA) (7, see also p. 16). The number of surviving ELBW infants is expected to increase in the near future mainly due to the recent clinical application of surfactant replacement therapy which has proven to be effective in improving the course of respiratory distress syndrome.
I . Bell EF, Warburton D, Stonestreet BS. Oh W. Effect of fluid administration on the development of symptomatic patent ductus arteriosus and congestive heart failure in premature infants. N Engl J Med 1980;302:598-604 2. Lucas A, Bloom SR, Aynsley-Green A. Gut hormones and “minimal enteral feeding”. Acta Paediatr Scand 1986;75:719-23 3. Minoli I, Moro G, Ovadia MF. Nasoduodenal feeding in high risk newborns. Acta Paediatr Scand 1978;67:161-8 4. Calciolari G, Moro G. Liberatore A, Minoli 1. Cerebral morbidity in VVLBW infants. In: Duc G. Huch A, Huch Reds The Very Low Birthweight Infant: A Challenge to Neonatology and Obstetrics. New York: Georg Thieme Verlag Stuttgart, 1990:77 5 . Moro G. Minoli 1. Survival with birth weight of less than 500 grams. Pediatrics I99 1;87:270-7 1 6 Ginsberg GH, Goldsmith PJ. Stedman MC. Intact survival and 20month follow-up of a 380-gram infant. J Perinatol 1990;10:330-3 7. Muraskas KJ, Carlson JN, Halsey C, Frederiksen MC, Sabbagha RE. Survival of a 280-g infant. N Engl J Med 1991;324:1598-9
Acknon,/ed~emenf.s.~This work was supported in part by the Consiglio Nazionale delle Ricerche (CNR), Target Project on Biotechnology and Bioinstrumentation. The authors are grateful to all colleagues of the Neonatal Intensive Care Unit and to the nursing staff, particularly skilled in the general management of high-risk newborns, for their devotion and love to all the tiny premature babies admitted to the Unit.
Management of extremely low-birth-weight infants Carlo Coccia, Marco Pezzani, Guido E Moro and Iolanda Minoli Depurlmenr of Perinalul Purhology. Proirinciul Marerniry Hospilul. Uni1:ersil.vof Milun. Milun. IIU!,~
Coccia C, Pezzani M, Moro GE, Minoli 1. Management of extremely low-birth-weight infants. Acta Prediatr 1992;Suppl 382: 10-12. Stockholm. ISSN 0803-5253 Better health care of women during pregnancy and delivery, improvement in neonatal intensive therapy and technology have led to a decrease in neonatal mortality and morbidity and to lower limits of birth weight and gestational age for survival. This paper refers to the management protocol used in the Department of Perinatal Pathology of the Provincial Maternity Hospital of Milan for extremely low-birth-weight (ELBW) infants (birth weight < 1000 g). In this hospital, all newborn infants presenting evidence of life, irrespective of birth weight and gestational age, are resuscitated and transferred to the Neonatal Intensive Care Unit (NICU) for clinical management. After the introduction of this protocol the mortality rate of ELBW infants dropped from 71.4% in 1977-78 to 48% in 1987-88. In a group of 72 ELBW infants with a mean birth weight of 850 g and a mean gestational age of 27 weeks, 80% presented a normal outcome, 12% presented a mild neurological impairment and 8% were affected by severe cerebral palsy at the age of two years. The intact survival of a newborn infant of 450 g at birth is also reported. G E Moro, Dii>isione di Patologin Perinatale, Istituto Ospedaliero Protlinciale p e r la M a t e r n i t a . V i a M . Melloni. 52, 20129 Milano, Italj’
We describe the management protocol used at the present time in our Neonatal Intensive Care Unit (NICU) in Milan for the extremely low-birth-weight (ELBW) infant (birth weight < 1000 g) and the outcome of a newborn with a birth weight of 450 g.
Management protocol of ELBW infants
prevent dehydration and to reduce the incidence of complications, such as necrotizing enterocolitis, cardiac failure and patent ductus arteriosus, which can be related to an excessive intake of fluid (I). Beginning with a total fluid intake of 60 ml/kg in the first day of life, we increase the fluid intake progressively in the first four days of life with a rate of 20 ml/kg/day and then use increments of 10 ml/kg/day to reach a maximum of 160-180 ml/kg/day between day 10 and 14. (5) Enteral feeding comprises subnutritional amounts of fresh human milk, administered from the second day of life, concomitantly with total parenteral nutrition. This minimal enteral feeding helps the physiological development of the gastrointestinal apparatus, stimulating the hormonal and enzymatic activities (2). Continuous nasoduodenal feeding avoids complications related to the introduction of food into the stomach and allows a precocious alimentation and an adequate caloric intake during the first days of life (3). (6) Early daily contact between mother and infant is encouraged for the psychophysical well-being of both.
( I ) Endotracheal intubation in the delivery room. As the first minutes of life are extremely important for survival and quality of life, endotracheal intubation is performed routinely in the delivery room, immediately after birth, in order to prevent alveolar collapse, excessive respiratory efforts, and metabolic and respiratory acidosis. (2) Early percutaneouscentral venous line placement. A percutaneous central venous catheter is inserted for parenteral nutrition and to reduce the frequency of stressful venipunctures. (3) Minimal handling and sterile procedures are essential to reduce the risk of neonatal infections. To avoid the stress of frequent manipulations, we concentrate several procedures together. When the baby is Results handled for blood samples, suctioning from the endotracheal tube, positioning of electrodes and baby clean- Following the introduction of this protocol, the moring are performed. Because of continuous transpyloric tality rate of the ELBW infants admitted to our NICU feeding, the infant is handled for enteral nutrition only decreased from 71.4%0in 1975-1978 to 48% in 1985every 2-3 days. 1988. Seventy-two ELBW infants (mean birth weight (4) Fluid intake is controlled accurately in order to 850 g and mean gestational age 27 weeks) admitted to
ACTA PRDIATR SUPPL 382 (19921
the NICU survived in the period 1985-1988. These babies were followed regularly with neurological evaluation during the first two years of life. Eighty percent presented a normal outcome, 12% mild neurological impairment and 8% were affected by severe cerebral Palsy (4).
Case report We recently reported the case of an infant with a birth weight of 450 g (5) and we can now summarize her clinical history and refer to her neurodevelopmental follow-up. Valentina L was born in the Provincial Maternity Hospital, Milan, on May 7, 1988, after 27 weeks gestation. She was the second child of a 37-year-old mother who had delivered a female child with a birth weight of 2190 g and a gestational age of 38 weeks four years previously. The maternal history revealed some cigarette smoking during pregnancy and ultrasonographic examinations had shown intrauterine growth retardation from the 22nd week of gestation. Owing to severe maternal eclampsia, the infant was delivered by cesarean section. Birth weight was 450 g, length 29.5 cm and head circumference 21 cm. Apgar score at 1 min was 1; consequently the infant was intubated with a nasotracheal tube (Portex No. 2) immediately after birth and ventilated with intermittent positive pressure ventilation and 100% oxygen. Apgar score at 5 min was 6. The infant was admitted to the NICU. A roentgenogram performed 4 h after birth showed a stage I1 respiratory distress syndrome and a right pneumothorax that resolved spontaneously in 36 h. The patient was mechanically ventilated continuously up to the 35th day of life. The maximum oxygen concentration (apart from 100% oxygen given at birth) was 80% for 16 h on the 26th day of life. A percutaneous central venous catheter was inserted for parenteral nutrition and on the second day of life an exchange transfusion was carried out through an umbilical venous catheter because of hyperbilirubinemia (9.5 mg/dl after 14 h of life). Several episodes of clinically asymptomatic hypoglycemia occurred in the first days of life in spite of high parenteral glucose intakes. On the second day of life, parenteral feeding was begun because of delayed passage of meconium and abdominal distension. A diagnosis of intestinal obstruction was confirmed by roentgenograms and, on the 10th day of life, surgery was performed. Intraoperative findings included a subatretic segment of distal ileum, just proximal to the ileocecal valve. Sparing the ileocecal valve and the terminal ileum, the atretic portion was removed and an end-to-end (onelayer) anastomosis was performed. Postoperatively, poor canalization with persistent abdominal distension and bile-stained fluid from the feeding tube were observed. Radiographic examination revealed a persist-
Munugemeni
of ELB W infunis
I1
ent intestinal obstruction and the abdomen was reexamined on the 23rd day of life. A stenosis with dilatation of the proximal ileal segment was evident at the level of the previous anastomosis and s o . a new resection, including the ileocecal valve, with an end-toend anastomosis between the ileum and the ascending colon, was performed. After the second operation, the baby had an uneventful recovery. On the 30th day of life enteral feeding was started with fresh mother’s milk. From the 49th day of life, the infant received fortified human milk from the bank until the 73rd day of life when artificial formula was started. The infant developed a retinopathy of prematurity at stage I that resolved spontaneously. During her stay in the NICU, all cranial scans performed were normal. When the infant was discharged at 5.5 months ofage, her weight was 2100 g, length 43.5 cm and head circumference 32 cm. Her clinical condition was satisfactory. Neurodei~elopmentdfollow-up The infant’s ultrasound brain scan and neurological state appeared normal at serial examinations during the first trimester of life. A small reduction in fine coordination and balance was detected in the first 9 months of life. These mild neurological signs disappeared at 12 months. Independent walking was reached at 21 months of age (18 months corrected age) and her neurological assessment appeared normal at the age of 22 months (19 months corrected age). Thus the mild neurological deficit detected during the first three trimesters may be considered as a transitory developmental delay in some neurological functions. At the last neurodevelopmental assessment at the chronological age of 46 months, the child presented a normal neurological state and developmental progress. The patient is a tiny child (weight 10070 g and length 91 cm at the age of 3 years and 1 1 months), uninhibited and interested in people and the environment. She has a good attitude to communication and social activity. She is able to concentrate her attention during spontaneous play and developmental tests. N o behavioural or autonomic problems were observed in the first years of life. She recently showed good adaptation to kindergarten, without any difficulty. Her general developmental quotient using the Griffith’s scale was 81 at 18 months corrected age; since the normal range of this test is 76 (borderline 73-79), her development could be considered normal. In subsequent developmental evaluations at 37 and 46 months of chronological age, general developmental quotients at the Griffith’s extension scale were 75.8% and 78%, respectively (borderline). In both cases, the general developmental quotient could still be considered within the normal range if score was related to corrected age. The child presented difficulties mostly in visuomotor and fine manipulation skills. In fact, in the “hand
12
C Coccia el a/.
ACTA PEDIATR SUPPL 382 (1992)
and eye coordination subscale” the subquotient was 64.8% at 37 months and 65.8% at 46 months of age. In the “hearing and speech subscale”, the subquotient was 75.8% at 37 months and 65.6% at 46 months of age. Speech was more delayed than language, and the child was able to produce short sentences of four words at 37 months of age. Also, in the “practical reasoning subscale”, in which language is widely requested, the score was below the range of normality. In conclusion, the child now presents a mild psychomotor delay at the borderline range, but an improvement in development with improvement of language and speech is expected.
Neonatologists will have to cope with some aspects of neonatology which are not yet completely clarified and standardized, such as handling, growth, nutritional status assessment and long-term neurodevelopmental follow-up of ELBW infants.
Conclusions
References
Valentina is not the only infant with a birth weight less than 500 g who survived with a normal neurodevelopmental outcome. Other cases have been reported recently: Heiko, born in Ludwigshafen/Rhein (Germany) with a birth weight of 460 g (H Karte, personal communication); Ramona, born in Bern (Switzerland) with a birth weight of 390 g (see p. 7); Monica, born in New Orleans (USA) with a birth weight of 380 g (6, see also p. 13); and the smallest infant, a female of 280 g, born in Maywood (USA) (7, see also p. 16). The number of surviving ELBW infants is expected to increase in the near future mainly due to the recent clinical application of surfactant replacement therapy which has proven to be effective in improving the course of respiratory distress syndrome.
I . Bell EF, Warburton D, Stonestreet BS. Oh W. Effect of fluid administration on the development of symptomatic patent ductus arteriosus and congestive heart failure in premature infants. N Engl J Med 1980;302:598-604 2. Lucas A, Bloom SR, Aynsley-Green A. Gut hormones and “minimal enteral feeding”. Acta Paediatr Scand 1986;75:719-23 3. Minoli I, Moro G, Ovadia MF. Nasoduodenal feeding in high risk newborns. Acta Paediatr Scand 1978;67:161-8 4. Calciolari G, Moro G. Liberatore A, Minoli 1. Cerebral morbidity in VVLBW infants. In: Duc G. Huch A, Huch Reds The Very Low Birthweight Infant: A Challenge to Neonatology and Obstetrics. New York: Georg Thieme Verlag Stuttgart, 1990:77 5 . Moro G. Minoli 1. Survival with birth weight of less than 500 grams. Pediatrics I99 1;87:270-7 1 6 Ginsberg GH, Goldsmith PJ. Stedman MC. Intact survival and 20month follow-up of a 380-gram infant. J Perinatol 1990;10:330-3 7. Muraskas KJ, Carlson JN, Halsey C, Frederiksen MC, Sabbagha RE. Survival of a 280-g infant. N Engl J Med 1991;324:1598-9
Acknon,/ed~emenf.s.~This work was supported in part by the Consiglio Nazionale delle Ricerche (CNR), Target Project on Biotechnology and Bioinstrumentation. The authors are grateful to all colleagues of the Neonatal Intensive Care Unit and to the nursing staff, particularly skilled in the general management of high-risk newborns, for their devotion and love to all the tiny premature babies admitted to the Unit.
