Necrotizing Enterocolitis
Following Intrauterine
By Catherine
A. Musemeche and Marleta Chicago, Illinois
l Intravascular intrauterine transfusion allows a more sophisticated and exact approach to the management of severe Rh hemolytic disease. This technique involves direct manipulation of the fetal umbilical vessels; its hazards include umbilical cord trauma and thrombosis or emboli. The consequences of such events in utero are largely unknown. In this case necrotizing enterocolitis occured in a full-term infant after three intrauterine intravascular transfusions. Copyright Q 1991 by W.B. Saunders Company INDEX WORDS: Necrotizing intrauterine transfusion.
enterocolitis;
cordocentesis;
P
ERCUTANEOUS umbilical blood sampling (cordocentesis) is being used with increasing frequency for in utero diagnosis and therapy.‘,’ The complication rates for cordocentesis have been reported at 9.4% and 7.1%, respectively.2 In addition to intrauterine death, complications include cord trauma, chorioamnionitis, and fetal arrythmias. This is a report of a case of necrotizing enterocolitis (NEC) that occurred in a 36-week gestation newborn who received three intravascular intrauterine blood transfusions (IUTs). CASE REPORT A white boy weighing 2,925 g was born at 36 weeks’ gestation to a 35year-old woman (gravida 3, para 2) who had been Rh-sensitized during her first pregnancy. The product of the first pregnancy was a healthy full-term boy who had no complications. During the second pregnancy the fetus was treated with IUTs without complications. The infant of the third pregnancy received three IUTs at 22 weeks, 30 weeks, and 32 weeks gestation. At birth the infant’s Apgar scores were 7 and 8. On physical examination he was not jaundiced and his abdomen was not distended. The initial hematocrit was 23 mg/dL. The total bilirubin was 4.7 mg/dL with a direct fraction of 0.9 mg/dL. The baby received a transfusion of Rh-negative blood after birth. He was begun on oral feedings at 1 day of age. On the second day of life he developed abdominal distention and radiographs of the abdomen showed extensive pneumatosis intestinalis. The baby was placed on orogastric suction and intravenous antibiotics. Twelve hours later he had free air on an abdominal x-ray. At operation, he had ischemic necrosis of the intestine from the midileum to the midtransverse colon. No distinct vessel thrombus was identified. We resected 30 cm of intestine including the ileocecal valve. A proximal ileostomy and distal mucus fistula were performed. Histological examination of the intestine was consistent with NEC. On the first postoperative day the baby’s bilirubin was 28.2 with a direct fraction of 6.3; this was treated with a double-volume exchange transfusion. He was maintained on phototherapy with subsequent resolution of the hyperbilirubinemia. An ultrasound scan of the head showed bilateral intraparenchymal hemorrhage on the second day of life. A subsequent computed tomography scan of the brain showed resolution of the hemorrhage. At 1 month of age we reanastomosed his intestine. He Joumaloffed/atric
Surgery,
Vol26,
No 12 (December),
1991: pp 1411-1412
Blood Transfusion
Reynolds
was discharged from the hospital 7 days after that formula feedings and has had no subsequent medical
operation problems.
on
DISCUSSION
Since the introduction of Rh(D) immune globulin (RhoGAM) in 1968 the incidence of Rh hemolytic disease has decreased. It occurs now when RhoGAM is not administered to Rh-negative women when indicated following delivery, abortion, or amniocentesis.3 Erythroblastosis fetalis (hemolysis of fetal red blood cells) results from transplacental passage of IgG antibodies. The spectrum of clinical manifestations depends on the individual immune response of the affected fetus and ranges from mild anemia and hyperbilirubinemia at birth to profound intrauterine anemia and death. Fetal anemia induces extramedullary hematopoiesis and secondary hepatosplenomegaly. In its most severe and advanced form (“hydrops fetalis”), portal hypertension, ascites, and anasarca eventually develop resulting in intrauterine or neonatal death. IUT serves (1) to correct fetal anemia and improve tissue oxygenation, and (2) to decrease fetal extramedullary hematopoiesis.3 The decision to perform IUT is based on spectrophotometric analysis of the quantity of bilirubin pigment in the fetus. IUTs for the treatment of erythroblastosis fetalis were first performed by Liley in 1963 using the intraperitoneal technique.4 This is performed by inserting a needle directly into the fetal abdomen using ultrasound guidance.3 The major danger to the fetus is trauma from the transfusing needle. Inadvertant needle placement in various organs of the fetus reported in the literature may or may not result in significant injury.5.h There is a risk of fetal death occuring after any IUT especially within 48 hours of the procedure. Turner et al reported a series of 461 pregnancies in which intraperitoneal IUT was used.’ There were 84 fetal deaths; 50% were associated with hydrops fetalis and 19% were directly attributed to the procedure itself. Procedural failures included hemothorax (3) liver laceration (2) sepsis (2) and generalized fetal trauma (9). Fatal pericardial tamponade after intraperitoneal transfusion has occured.’ From the Division of Pediattic Surgery, Department of Surgery, Northwestern University, Chicago, IL. Address reprint requests to Marleta Reynolds, MD, ChildrenS Memorial Hospital, 2300 ChildrenS Plaza, Chicago. IL 60614. Copyright o 1991 by W.B. Saunders Cornpam 0022.346819112612-0019$03.0010 1411
MUSEMECHE
1412
Hyperbilirubinemia secondary to hemolysis of an intraperitoneal blood transfusion was reported in one infant in whom there was delayed absorption of the intraperitoneal blood. This resulted in an elevated bilirubin at birth, which was refractory to phototherapy and 11 double-volume exchange transfusions. The hyperbilirubinemia resolved only after a peritoneal lavage was performed to wash out the residual transfused blood in the baby’s peritoneal cavity.8 In 1978, White et al reported a series of 30 infants who survived intraperitoneal IUT.9 One patient in this series had meconium ileus and one patient developed NEC. There was also an increased incidence of umbilical and inguinal hernias. In 1981, a technique for direct fetal intravascular blood transfusion was described by Rodeck et al.” Although technically demanding, this procedure allows exact measurements of fetal hematocrits pretransfusion and posttransfusion and provides a direct and certain route for in utero transfusion.’ Currently, the technique entails the use of ultrasound guidance for percutaneous introduction of a 20-gauge needle into a cord vessel.” Cordocentesis can also be used to determine fetal karyotype, assess acid-base status, and diagnose in utero infection.’ As with intraperitoneal transfusions, needle placement can be complicated by fetal position and movement. Berkowitz et al’ described 8 infants with severe erythroblastosis treated with intravascular IUT. Needle tip dislodgement occured in four patients and suspected cord trauma in one of these. There was one possible procedure-related death in this series.’ In a recent review by Pielet et al, complications were
AND
REYNOLDS
reported in 6 of 64 fetuses who underwent intravascular transfusion.* These included fetal cardiac decelerations and arrythmias in four babies and chorioamnionitis in one. At birth the umbilical artery was noted to be clotted in one infant. There was an obvious cord hematoma in one infant and an arteriovenous malformation of the cord was noted in another. Postnatal complications included neonatal non-A, non-B hepatitis in one infant. Of the six patients with complications, three did not survive. Although umbilical cord trauma has been documented during and after IUT, the postnatal effects of direct manipulation and puncture of the umbilical vessels in utero is not known. Umbilical vessel thrombosis and microembolism from umbilical vessel catheters placed after birth have been implicated in the pathogenesis of NEC.‘* Intravascular transfusion in the fetal period may also result in hyperviscosity. Hyperviscosity in combination with poor mesenteric microcirculation can lead to ischemia of the intestine and predisposes to NEC. Wilson et al found polycythemia to be the most common antecedent condition in babies weighing more than 2,500 g who developed NEC.13 NEC has been reported in infants before and after exchange transfusion for polycythemia.14 In one study the incidence of NEC was higher in infants treated with exchange transfusion for neonatal hyperviscosity than in those who were observed.” NEC is a previously undocumented complication of intravascular IUT. In the future the use of cordocentesis and intravascular IUT may be recognized as increased risk factors in the development of NEC.
REFERENCES 1. Berkowitz RL, Chitkara U, Goldberg JD, et al: Intrauterine intravascular transfusions for severe red blood cell isoirnmunization: Ultrasound-guided percutaneous approach. Am J Obstet Gynecol155:574,1986 2. Pielet BW, Socol ML, MacGregor SN, et al: Cordocentesis: An appraisal of risks. Am J Obstet Gynecol6:1497-1500,1988 3. Berkowitz RL: Intrauterine transfusions 1980: An update. Clin Perinatol7:285-297,198O 4. Liley AW: Intrauterine transfusion of foetus in haemolytic disease. Br Med J 2:1107-1109,1963 5. Bowman JM: The management of Rh-isoimmunization. Obstet Gynecol52:1-16, 1978 6. Liggins GC: Fetal transfusion by the impaling technique. Obstet Gynecol27:617-621,1966 7. Turner JH, Hutchinson DL, Hayashi ‘IT, et al: Fetal and maternal risks associated with intrauterine transfusion procedures. Am J Obstet Gynecol123:251-256,1975 8. Rajagopalan I, Katz BZ: Hyperbilirubinemia secondary to hemolysis of intrauterine intraperitoneal blood transfusion. Clin Pediatr 9:511-512, 1984
9. White CA, Goplerud CP, Kisker CT, et al: Intrauterine fetal transfusion, 19651976, with an assessment of surviving children. Am J Obstet Gynecol130:933-942,197s 10. Rodeck CH, Nicolaides KH, Warsof LS, et al: The management of severe rhesus isoimmunization by fetoscopic intravascular transfusions. Am J Obstet Gynecol 150:769-774,1984 11. Berkowitz RL, Chitkara U, Wilkins I: Technical aspects of intravascular intrauterine transfusions: Lessons learned from thirtythree procedures. Am J Obstet Gynecol157:4-9,1987 12. Lehmiller DJ, Kanto WP Jr: Relationships of mesenteric thromboembolism, oral feeding, and necrotizing enterocolitis. J Pediatr 92:96-100,197s 13. Wilson R, de1 Portillo M, Schmidt E, et al: Risk factors for necrotizing enterocolitis in infants weighing more than 2000 grams at birth: A case-control study. Pediatrics 71:19-22, 1983 14. Leake RD, Thanopoulos B, Nieberg R: Hyperviscosity syndrome associated with necrotizing enterocolitis. Am J Dis Child X29:1192-1194, 1975 15. Black V, Lubchenco LO, Koops BL, et al: Neonatal hyperviscosity: Randomized study of pertial plasma exchange in altering long-term outcome. Pediatr Res 16:279A, 1982 (abstr)
Following Intrauterine
By Catherine
A. Musemeche and Marleta Chicago, Illinois
l Intravascular intrauterine transfusion allows a more sophisticated and exact approach to the management of severe Rh hemolytic disease. This technique involves direct manipulation of the fetal umbilical vessels; its hazards include umbilical cord trauma and thrombosis or emboli. The consequences of such events in utero are largely unknown. In this case necrotizing enterocolitis occured in a full-term infant after three intrauterine intravascular transfusions. Copyright Q 1991 by W.B. Saunders Company INDEX WORDS: Necrotizing intrauterine transfusion.
enterocolitis;
cordocentesis;
P
ERCUTANEOUS umbilical blood sampling (cordocentesis) is being used with increasing frequency for in utero diagnosis and therapy.‘,’ The complication rates for cordocentesis have been reported at 9.4% and 7.1%, respectively.2 In addition to intrauterine death, complications include cord trauma, chorioamnionitis, and fetal arrythmias. This is a report of a case of necrotizing enterocolitis (NEC) that occurred in a 36-week gestation newborn who received three intravascular intrauterine blood transfusions (IUTs). CASE REPORT A white boy weighing 2,925 g was born at 36 weeks’ gestation to a 35year-old woman (gravida 3, para 2) who had been Rh-sensitized during her first pregnancy. The product of the first pregnancy was a healthy full-term boy who had no complications. During the second pregnancy the fetus was treated with IUTs without complications. The infant of the third pregnancy received three IUTs at 22 weeks, 30 weeks, and 32 weeks gestation. At birth the infant’s Apgar scores were 7 and 8. On physical examination he was not jaundiced and his abdomen was not distended. The initial hematocrit was 23 mg/dL. The total bilirubin was 4.7 mg/dL with a direct fraction of 0.9 mg/dL. The baby received a transfusion of Rh-negative blood after birth. He was begun on oral feedings at 1 day of age. On the second day of life he developed abdominal distention and radiographs of the abdomen showed extensive pneumatosis intestinalis. The baby was placed on orogastric suction and intravenous antibiotics. Twelve hours later he had free air on an abdominal x-ray. At operation, he had ischemic necrosis of the intestine from the midileum to the midtransverse colon. No distinct vessel thrombus was identified. We resected 30 cm of intestine including the ileocecal valve. A proximal ileostomy and distal mucus fistula were performed. Histological examination of the intestine was consistent with NEC. On the first postoperative day the baby’s bilirubin was 28.2 with a direct fraction of 6.3; this was treated with a double-volume exchange transfusion. He was maintained on phototherapy with subsequent resolution of the hyperbilirubinemia. An ultrasound scan of the head showed bilateral intraparenchymal hemorrhage on the second day of life. A subsequent computed tomography scan of the brain showed resolution of the hemorrhage. At 1 month of age we reanastomosed his intestine. He Joumaloffed/atric
Surgery,
Vol26,
No 12 (December),
1991: pp 1411-1412
Blood Transfusion
Reynolds
was discharged from the hospital 7 days after that formula feedings and has had no subsequent medical
operation problems.
on
DISCUSSION
Since the introduction of Rh(D) immune globulin (RhoGAM) in 1968 the incidence of Rh hemolytic disease has decreased. It occurs now when RhoGAM is not administered to Rh-negative women when indicated following delivery, abortion, or amniocentesis.3 Erythroblastosis fetalis (hemolysis of fetal red blood cells) results from transplacental passage of IgG antibodies. The spectrum of clinical manifestations depends on the individual immune response of the affected fetus and ranges from mild anemia and hyperbilirubinemia at birth to profound intrauterine anemia and death. Fetal anemia induces extramedullary hematopoiesis and secondary hepatosplenomegaly. In its most severe and advanced form (“hydrops fetalis”), portal hypertension, ascites, and anasarca eventually develop resulting in intrauterine or neonatal death. IUT serves (1) to correct fetal anemia and improve tissue oxygenation, and (2) to decrease fetal extramedullary hematopoiesis.3 The decision to perform IUT is based on spectrophotometric analysis of the quantity of bilirubin pigment in the fetus. IUTs for the treatment of erythroblastosis fetalis were first performed by Liley in 1963 using the intraperitoneal technique.4 This is performed by inserting a needle directly into the fetal abdomen using ultrasound guidance.3 The major danger to the fetus is trauma from the transfusing needle. Inadvertant needle placement in various organs of the fetus reported in the literature may or may not result in significant injury.5.h There is a risk of fetal death occuring after any IUT especially within 48 hours of the procedure. Turner et al reported a series of 461 pregnancies in which intraperitoneal IUT was used.’ There were 84 fetal deaths; 50% were associated with hydrops fetalis and 19% were directly attributed to the procedure itself. Procedural failures included hemothorax (3) liver laceration (2) sepsis (2) and generalized fetal trauma (9). Fatal pericardial tamponade after intraperitoneal transfusion has occured.’ From the Division of Pediattic Surgery, Department of Surgery, Northwestern University, Chicago, IL. Address reprint requests to Marleta Reynolds, MD, ChildrenS Memorial Hospital, 2300 ChildrenS Plaza, Chicago. IL 60614. Copyright o 1991 by W.B. Saunders Cornpam 0022.346819112612-0019$03.0010 1411
MUSEMECHE
1412
Hyperbilirubinemia secondary to hemolysis of an intraperitoneal blood transfusion was reported in one infant in whom there was delayed absorption of the intraperitoneal blood. This resulted in an elevated bilirubin at birth, which was refractory to phototherapy and 11 double-volume exchange transfusions. The hyperbilirubinemia resolved only after a peritoneal lavage was performed to wash out the residual transfused blood in the baby’s peritoneal cavity.8 In 1978, White et al reported a series of 30 infants who survived intraperitoneal IUT.9 One patient in this series had meconium ileus and one patient developed NEC. There was also an increased incidence of umbilical and inguinal hernias. In 1981, a technique for direct fetal intravascular blood transfusion was described by Rodeck et al.” Although technically demanding, this procedure allows exact measurements of fetal hematocrits pretransfusion and posttransfusion and provides a direct and certain route for in utero transfusion.’ Currently, the technique entails the use of ultrasound guidance for percutaneous introduction of a 20-gauge needle into a cord vessel.” Cordocentesis can also be used to determine fetal karyotype, assess acid-base status, and diagnose in utero infection.’ As with intraperitoneal transfusions, needle placement can be complicated by fetal position and movement. Berkowitz et al’ described 8 infants with severe erythroblastosis treated with intravascular IUT. Needle tip dislodgement occured in four patients and suspected cord trauma in one of these. There was one possible procedure-related death in this series.’ In a recent review by Pielet et al, complications were
AND
REYNOLDS
reported in 6 of 64 fetuses who underwent intravascular transfusion.* These included fetal cardiac decelerations and arrythmias in four babies and chorioamnionitis in one. At birth the umbilical artery was noted to be clotted in one infant. There was an obvious cord hematoma in one infant and an arteriovenous malformation of the cord was noted in another. Postnatal complications included neonatal non-A, non-B hepatitis in one infant. Of the six patients with complications, three did not survive. Although umbilical cord trauma has been documented during and after IUT, the postnatal effects of direct manipulation and puncture of the umbilical vessels in utero is not known. Umbilical vessel thrombosis and microembolism from umbilical vessel catheters placed after birth have been implicated in the pathogenesis of NEC.‘* Intravascular transfusion in the fetal period may also result in hyperviscosity. Hyperviscosity in combination with poor mesenteric microcirculation can lead to ischemia of the intestine and predisposes to NEC. Wilson et al found polycythemia to be the most common antecedent condition in babies weighing more than 2,500 g who developed NEC.13 NEC has been reported in infants before and after exchange transfusion for polycythemia.14 In one study the incidence of NEC was higher in infants treated with exchange transfusion for neonatal hyperviscosity than in those who were observed.” NEC is a previously undocumented complication of intravascular IUT. In the future the use of cordocentesis and intravascular IUT may be recognized as increased risk factors in the development of NEC.
REFERENCES 1. Berkowitz RL, Chitkara U, Goldberg JD, et al: Intrauterine intravascular transfusions for severe red blood cell isoirnmunization: Ultrasound-guided percutaneous approach. Am J Obstet Gynecol155:574,1986 2. Pielet BW, Socol ML, MacGregor SN, et al: Cordocentesis: An appraisal of risks. Am J Obstet Gynecol6:1497-1500,1988 3. Berkowitz RL: Intrauterine transfusions 1980: An update. Clin Perinatol7:285-297,198O 4. Liley AW: Intrauterine transfusion of foetus in haemolytic disease. Br Med J 2:1107-1109,1963 5. Bowman JM: The management of Rh-isoimmunization. Obstet Gynecol52:1-16, 1978 6. Liggins GC: Fetal transfusion by the impaling technique. Obstet Gynecol27:617-621,1966 7. Turner JH, Hutchinson DL, Hayashi ‘IT, et al: Fetal and maternal risks associated with intrauterine transfusion procedures. Am J Obstet Gynecol123:251-256,1975 8. Rajagopalan I, Katz BZ: Hyperbilirubinemia secondary to hemolysis of intrauterine intraperitoneal blood transfusion. Clin Pediatr 9:511-512, 1984
9. White CA, Goplerud CP, Kisker CT, et al: Intrauterine fetal transfusion, 19651976, with an assessment of surviving children. Am J Obstet Gynecol130:933-942,197s 10. Rodeck CH, Nicolaides KH, Warsof LS, et al: The management of severe rhesus isoimmunization by fetoscopic intravascular transfusions. Am J Obstet Gynecol 150:769-774,1984 11. Berkowitz RL, Chitkara U, Wilkins I: Technical aspects of intravascular intrauterine transfusions: Lessons learned from thirtythree procedures. Am J Obstet Gynecol157:4-9,1987 12. Lehmiller DJ, Kanto WP Jr: Relationships of mesenteric thromboembolism, oral feeding, and necrotizing enterocolitis. J Pediatr 92:96-100,197s 13. Wilson R, de1 Portillo M, Schmidt E, et al: Risk factors for necrotizing enterocolitis in infants weighing more than 2000 grams at birth: A case-control study. Pediatrics 71:19-22, 1983 14. Leake RD, Thanopoulos B, Nieberg R: Hyperviscosity syndrome associated with necrotizing enterocolitis. Am J Dis Child X29:1192-1194, 1975 15. Black V, Lubchenco LO, Koops BL, et al: Neonatal hyperviscosity: Randomized study of pertial plasma exchange in altering long-term outcome. Pediatr Res 16:279A, 1982 (abstr)
