JOURNAL OF TROPICAL PEDIATRICS, VOL. 60, NO. 2, 2014
Case Report
Cytomegalovirus Infection in Preterm Triplets Transmitted via Breast Milk by Gamze Demirel,1 Istemi Han Celik,2 Fuat Emre Canpolat,3 and Ugur Dilmen3,4 1 Division of Neonatology, Neonatal Intensive Care Unit, Samsun Maternal and Child Health Hospital, Samsun, Turkey 2 Division of Neonatology, Etlik Zubeyde Hanım Maternity Teaching Hospital, Ankara, Turkey 3 Division of Neonatology, Neonatal Intensive Care Unit1, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey 4 Department of Pediatrics, Yildirim Beyazıt University, Ankara, Turkey
Summary Cytomegalovirus (CMV) may transmit perinatally or from breast milk. The risk for development of symptomatic CMV disease in very-low-birth-weight premature infants after transmission from maternal breast milk is not clear. There are scarce data in the literature about congenital CMV infection in multiple pregnancies, being mostly with twin gestations. Here we present a unique case of triplets with CMV infection transmitted via breast milk. Key words: Cytomegalovirus, triplet, breast milk.
Introduction Cytomegalovirus (CMV) is an enveloped DNA virus that is the most common cause of congenital infection affecting 0.3–2% of liveborn infants [1]. The fetus can be infected in any trimester of pregnancy after primary, reactivation or reinfection of CMV [2]. As gestational age increases, viral transmission rate progressively increases, but infections in early gestation probably result in more severe congenital disease [3, 4]. CMV may also transmit perinatally from infected maternal genital secretions at delivery or from breast milk [2]. The risk for development of symptomatic CMV disease in verylow-birth-weight premature infants after transmission from maternal breast milk is not clear. Moreover, there are scarce data in the literature about congenital CMV infection in multiple pregnancies, being mostly with twin gestations. Here we describe a unique case of CMV infection in triplets transmitted via breast milk. Case Reports Triplet 1 A 1080-g 29-week male infant was born, as a triplet, to a 33-year-old female with cesarean section. Apgar
scores were 7 and 9 at 1 and 5 min, respectively. The infant had respiratory distress soon after birth and was transported to a neonatal intensive care unit where nasal continuous airway pressure (nCPAP) was performed. An umbilical venous catheter was placed. Blood cultures and a complete blood count were drawn and penicillin-G and netilmicin therapies were started empirically. After acute respiratory problems, he progressed well until on Day 43, when he developed mild cholestasis. The investigation of the etiology of cholestasis revealed positive CMV immunoglobulin G (IgG) and immunoglobulin M (IgM) tests in serum. Afterwards, CMV was isolated from his urine (1 257 000 copy/ml) and CMV polymerase chain reaction (PCR) in his serum was 1000 copy/ ml. Routine screening of the mother for CMV at birth was negative. The mother was seronegative for CMV and CMV PCR was negative at the time of diagnosis. CMV viral load at breast milk was 100 000 copy/ml. Eye examination for CMV involvement was negative, and there was no pathology related to CMV in cranial ultrasonography (USG). The triamniotic–trichorionic placentas were not fused to each other, and placental pathology was normal. Because there was no organ involvement, no therapy was started. Cholestasis resolved spontaneously within few days and the patient was discharged at Day 69.
ß The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected] doi:10.1093/tropej/fmt087 Advance Access published on 29 October 2013
168
Downloaded from http://tropej.oxfordjournals.org/ at University of Notre Dame on August 22, 2014
Gamze Demirel wrote the first draft of the manuscript. No payment was given to anyone to produce the manuscript. Correspondence: Gamze Demirel, Neonatal Intensive Care Unit, Samsun Maternal and Child Health Hospital, Samsun, Turkey. Tel: þ90 532 4540156; E-mail .
CASE REPORT
Triplet 3 A 750-g 29-week male infant was born, as a triplet, to a 33-year-old female with cesarean section. Apgar scores were 6 and 8 at 1 and 5 min, respectively. The infant had respiratory distress and was transported to a Level-III neonatal intensive care unit; surfactant was given by the endotracheal route and nCPAP was performed. An umbilical venous catheter was placed. Blood cultures and a complete blood count were drawn and penicillin-G and netilmicin therapies were started empirically. After early problems, antibiotic therapy was started for suspected necrotizing enterocolitis. He progressed well until Day 37. Acute-phase reactants were positive and empirical vancomycin and amikacin therapies were started. C-reactive protein and interleukin-6 levels were still high due to the antibiotic therapy. As CMV was detected at his triplets, he was evaluated in aspect of CMV infection. CMV IgM and IgG were negative at serum, but serum CMV PCR was 157 copy/ml and urine CMV PCR was 68 700 copy/ml. CMV viral load at breast milk was 100 000 copy/ml. Eye examination for CMV involvement was negative, and there was no pathology related to CMV in cranial USG. Because there was no organ involvement, no therapy was given. The patient was discharged at Day 69 at the same time with his triplets. Discussion This is the first report on triplet preterm infants with CMV infection transmitted via breast milk. There is clear evidence that transmission of CMV occurs via Journal of Tropical Pediatrics
Vol. 60, No. 2
breast milk [5]. During breastfeeding, viral reactivation can occur in the mammary glands of the women who are positive for anti-CMV IgG antibodies and CMV may be generally excreted in the milk [6]. Because the incubation time of CMV infection is between 30 and 120 days, mother-to-infant infections transmitted via breast milk should not occur until at least 6 weeks after delivery, as seen in our triplets (sixth week) [7]. Although perinatal CMV infection has practically no consequences in term neonates, it may cause a severe symptomatic disease in preterm newborns [8, 9]. The precise risk for development of symptomatic CMV disease in very-low-birth-weight premature infants after transmission from maternal breast milk is not clear, although severe disease has been described in this setting. Also, the course and progression of CMV infection in multiple gestations is unclear. There is no accurate means to predict the sequelae of CMV infection in triplets or in terms of transmission, as in our report via breast milk [10, 11]. Rarely, congenital CMV infection may appear in multiple pregnancies; there are scarce data about this in literature, mostly with twin gestations [12–15]. Many factors influence the transmission rates and the severity of the infection, such as maternal and fetal immune status and viral strain virulence [16]. Although same maternal factors and viral strain virulence may be present, sometimes, perinatal outcome may be different, such as reported by Wu et al [10], one fetus did not survive and the other survived in a monozygotic twin pregnancy infected with congenital CMV infection. Kitajima et al [11] reported intrauterine CMV infection in triplets, each of whom showed differential transmission, placental pathology and postnatal outcome, and to our knowledge, this was the first report with CMV infection in triplets. The placentas were triamniotic– trichorionic and different in terms of virus involvement. In conclusion, this is the first report consisting of CMV infection in triplets transmitted via breast milk. All of the infants had clinical findings of nonspecific infection, but none of the infants had multiorgan involvement related to CMV infection. We should consider CMV infection in infants whose acute-phase reactants are unresponsive to antibiotic therapy. Long-term neurodevelopmental outcome and hearing of the infants will be assessed in the near future. References 1. Lazzarotto T, Gabrielli L, Foschini MP, et al. Congenital cytomegalovirus infection in twin pregnancies: viral load in the amniotic fluid and pregnancy outcome. Pediatrics 2003;112:e153–7. 2. Griffiths PD. Strategies to prevent CMV infection in the neonate. Semin Neonatol 2002;7:293–9. 169
Downloaded from http://tropej.oxfordjournals.org/ at University of Notre Dame on August 22, 2014
Triplet 2 A 990-g 29-week male infant was born, as a triplet, to a 33-year-old female with cesarean section. Apgar scores were 7 and 9 at 1 and 5 min, respectively. The infant was transported to a neonatal intensive care unit because of respiratory distress and nCPAP was performed. An umbilical venous catheter was placed. Blood cultures and a complete blood count were drawn and penicillin-G and netilmicin therapies were started empirically. Oral ibuprofen was started for the treatment of patent ductus arteriosus. On postnatal Day 38, antibiotic therapy was started for late-onset neonatal sepsis. Due to large spectrum of antibiotics, acute-phase reactants did not decrease. As CMV IgM of the other triplet was positive, he was evaluated in aspect of CMV infection. Serum CMV IgM was 75.4, IgG was positive, serum CMV PCR was 8400 copy/ml and urine CMV virus load was 1 410 000 copy/ml. CMV viral load at breast milk was 100 000 copy/ml. Eye examination for CMV retinitis was negative, and there was no pathology related to CMV in cranial USG. Because there was no organ involvement, no therapy was given. The patient was discharged at Day 69.
CASE REPORT
170
10. Wu HY, Huang SC, Huang HC, et al. Cytomegalovirus infection and fetal death in one monozygotic twin. Taiwan J Obstet Gynecol 2011;50:230–2. 11. Kitajima J, Inoue H, Ohga S, et al. Differential transmission and postnatal outcomes in triplets with intrauterine cytomegalovirus infection. Pediatr Dev Pathol 2012;15:151–5. 12. Ahlfors K, Ivarsson SA, Nilsson H. On the unpredictable development of congenital cytomegalovirus infection. A study in twins. Early Hum Dev 1988;18: 125–35. 13. Seguin J, Cho CT. Congenital cytomegalovirus infection in one monozygotic twin. JAMA 1988;260: 3277. 14. Baker ER, Eberhardt H, Brown ZA. ‘‘Stuck twin’’ syndrome associated with congenital cytomegalovirus infection. Am J Perinatol 1993;10:81–3. 15. Bataille H, Elgellab A, Toussaint P, et al. Twin pregnancy and congenital cytomegalovirus infection with different outcomes. Arch Pediatr 1998;5:1168. 16. Yinon Y, Yagel S, Tepperberg-Dikawa M, et al. Prenatal diagnosis and outcome of congenital cytomegalovirus infection in twin pregnancies. BJOG 2006;11:295–300.
Journal of Tropical Pediatrics
Vol. 60, No. 2
Downloaded from http://tropej.oxfordjournals.org/ at University of Notre Dame on August 22, 2014
3. Nigro G, Adler SP, La Torre R, et al. Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 2005;353:1350–62. 4. Pass RF, Fowler KB, Boppana SB, et al. Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome. J Clin Virol 2006;35:216–20. 5. Stagno S, Cloud GA. Working parents: the impact of day care and breast-feeding on cytomegalovirus infections in offspring. Proc Natl Acad Sci USA 1994; 91:2384–9. 6. Hamprecht K, Goelz R, Maschmann J. Breast milk and cytomegalovirus infection in preterm infants. Early Hum Dev 2005;81:989–96. 7. Chiavarini M, Bragetti P, Sensini A, et al. Breastfeeding and transmission of cytomegalovirus to preterm infants. Case report and kinetic of CMV-DNA in breast milk. Ital J Pediatr 2011;37:6. 8. Jim WT, Shu CH, Chiu NC, et al. Transmission of cytomegalovirus from mothers to preterm infants by breast milk. Pediatr Infect Dis J 2004;23:848–851. 9. Maschmann J, Hamprecht K, Dietz K, et al. Cytomegalovirus infection of extremely low-birth weight infants via breast milk. Clin Infect Dis 2001; 33:1998–2003.
Case Report
Cytomegalovirus Infection in Preterm Triplets Transmitted via Breast Milk by Gamze Demirel,1 Istemi Han Celik,2 Fuat Emre Canpolat,3 and Ugur Dilmen3,4 1 Division of Neonatology, Neonatal Intensive Care Unit, Samsun Maternal and Child Health Hospital, Samsun, Turkey 2 Division of Neonatology, Etlik Zubeyde Hanım Maternity Teaching Hospital, Ankara, Turkey 3 Division of Neonatology, Neonatal Intensive Care Unit1, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey 4 Department of Pediatrics, Yildirim Beyazıt University, Ankara, Turkey
Summary Cytomegalovirus (CMV) may transmit perinatally or from breast milk. The risk for development of symptomatic CMV disease in very-low-birth-weight premature infants after transmission from maternal breast milk is not clear. There are scarce data in the literature about congenital CMV infection in multiple pregnancies, being mostly with twin gestations. Here we present a unique case of triplets with CMV infection transmitted via breast milk. Key words: Cytomegalovirus, triplet, breast milk.
Introduction Cytomegalovirus (CMV) is an enveloped DNA virus that is the most common cause of congenital infection affecting 0.3–2% of liveborn infants [1]. The fetus can be infected in any trimester of pregnancy after primary, reactivation or reinfection of CMV [2]. As gestational age increases, viral transmission rate progressively increases, but infections in early gestation probably result in more severe congenital disease [3, 4]. CMV may also transmit perinatally from infected maternal genital secretions at delivery or from breast milk [2]. The risk for development of symptomatic CMV disease in verylow-birth-weight premature infants after transmission from maternal breast milk is not clear. Moreover, there are scarce data in the literature about congenital CMV infection in multiple pregnancies, being mostly with twin gestations. Here we describe a unique case of CMV infection in triplets transmitted via breast milk. Case Reports Triplet 1 A 1080-g 29-week male infant was born, as a triplet, to a 33-year-old female with cesarean section. Apgar
scores were 7 and 9 at 1 and 5 min, respectively. The infant had respiratory distress soon after birth and was transported to a neonatal intensive care unit where nasal continuous airway pressure (nCPAP) was performed. An umbilical venous catheter was placed. Blood cultures and a complete blood count were drawn and penicillin-G and netilmicin therapies were started empirically. After acute respiratory problems, he progressed well until on Day 43, when he developed mild cholestasis. The investigation of the etiology of cholestasis revealed positive CMV immunoglobulin G (IgG) and immunoglobulin M (IgM) tests in serum. Afterwards, CMV was isolated from his urine (1 257 000 copy/ml) and CMV polymerase chain reaction (PCR) in his serum was 1000 copy/ ml. Routine screening of the mother for CMV at birth was negative. The mother was seronegative for CMV and CMV PCR was negative at the time of diagnosis. CMV viral load at breast milk was 100 000 copy/ml. Eye examination for CMV involvement was negative, and there was no pathology related to CMV in cranial ultrasonography (USG). The triamniotic–trichorionic placentas were not fused to each other, and placental pathology was normal. Because there was no organ involvement, no therapy was started. Cholestasis resolved spontaneously within few days and the patient was discharged at Day 69.
ß The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected] doi:10.1093/tropej/fmt087 Advance Access published on 29 October 2013
168
Downloaded from http://tropej.oxfordjournals.org/ at University of Notre Dame on August 22, 2014
Gamze Demirel wrote the first draft of the manuscript. No payment was given to anyone to produce the manuscript. Correspondence: Gamze Demirel, Neonatal Intensive Care Unit, Samsun Maternal and Child Health Hospital, Samsun, Turkey. Tel: þ90 532 4540156; E-mail .
CASE REPORT
Triplet 3 A 750-g 29-week male infant was born, as a triplet, to a 33-year-old female with cesarean section. Apgar scores were 6 and 8 at 1 and 5 min, respectively. The infant had respiratory distress and was transported to a Level-III neonatal intensive care unit; surfactant was given by the endotracheal route and nCPAP was performed. An umbilical venous catheter was placed. Blood cultures and a complete blood count were drawn and penicillin-G and netilmicin therapies were started empirically. After early problems, antibiotic therapy was started for suspected necrotizing enterocolitis. He progressed well until Day 37. Acute-phase reactants were positive and empirical vancomycin and amikacin therapies were started. C-reactive protein and interleukin-6 levels were still high due to the antibiotic therapy. As CMV was detected at his triplets, he was evaluated in aspect of CMV infection. CMV IgM and IgG were negative at serum, but serum CMV PCR was 157 copy/ml and urine CMV PCR was 68 700 copy/ml. CMV viral load at breast milk was 100 000 copy/ml. Eye examination for CMV involvement was negative, and there was no pathology related to CMV in cranial USG. Because there was no organ involvement, no therapy was given. The patient was discharged at Day 69 at the same time with his triplets. Discussion This is the first report on triplet preterm infants with CMV infection transmitted via breast milk. There is clear evidence that transmission of CMV occurs via Journal of Tropical Pediatrics
Vol. 60, No. 2
breast milk [5]. During breastfeeding, viral reactivation can occur in the mammary glands of the women who are positive for anti-CMV IgG antibodies and CMV may be generally excreted in the milk [6]. Because the incubation time of CMV infection is between 30 and 120 days, mother-to-infant infections transmitted via breast milk should not occur until at least 6 weeks after delivery, as seen in our triplets (sixth week) [7]. Although perinatal CMV infection has practically no consequences in term neonates, it may cause a severe symptomatic disease in preterm newborns [8, 9]. The precise risk for development of symptomatic CMV disease in very-low-birth-weight premature infants after transmission from maternal breast milk is not clear, although severe disease has been described in this setting. Also, the course and progression of CMV infection in multiple gestations is unclear. There is no accurate means to predict the sequelae of CMV infection in triplets or in terms of transmission, as in our report via breast milk [10, 11]. Rarely, congenital CMV infection may appear in multiple pregnancies; there are scarce data about this in literature, mostly with twin gestations [12–15]. Many factors influence the transmission rates and the severity of the infection, such as maternal and fetal immune status and viral strain virulence [16]. Although same maternal factors and viral strain virulence may be present, sometimes, perinatal outcome may be different, such as reported by Wu et al [10], one fetus did not survive and the other survived in a monozygotic twin pregnancy infected with congenital CMV infection. Kitajima et al [11] reported intrauterine CMV infection in triplets, each of whom showed differential transmission, placental pathology and postnatal outcome, and to our knowledge, this was the first report with CMV infection in triplets. The placentas were triamniotic– trichorionic and different in terms of virus involvement. In conclusion, this is the first report consisting of CMV infection in triplets transmitted via breast milk. All of the infants had clinical findings of nonspecific infection, but none of the infants had multiorgan involvement related to CMV infection. We should consider CMV infection in infants whose acute-phase reactants are unresponsive to antibiotic therapy. Long-term neurodevelopmental outcome and hearing of the infants will be assessed in the near future. References 1. Lazzarotto T, Gabrielli L, Foschini MP, et al. Congenital cytomegalovirus infection in twin pregnancies: viral load in the amniotic fluid and pregnancy outcome. Pediatrics 2003;112:e153–7. 2. Griffiths PD. Strategies to prevent CMV infection in the neonate. Semin Neonatol 2002;7:293–9. 169
Downloaded from http://tropej.oxfordjournals.org/ at University of Notre Dame on August 22, 2014
Triplet 2 A 990-g 29-week male infant was born, as a triplet, to a 33-year-old female with cesarean section. Apgar scores were 7 and 9 at 1 and 5 min, respectively. The infant was transported to a neonatal intensive care unit because of respiratory distress and nCPAP was performed. An umbilical venous catheter was placed. Blood cultures and a complete blood count were drawn and penicillin-G and netilmicin therapies were started empirically. Oral ibuprofen was started for the treatment of patent ductus arteriosus. On postnatal Day 38, antibiotic therapy was started for late-onset neonatal sepsis. Due to large spectrum of antibiotics, acute-phase reactants did not decrease. As CMV IgM of the other triplet was positive, he was evaluated in aspect of CMV infection. Serum CMV IgM was 75.4, IgG was positive, serum CMV PCR was 8400 copy/ml and urine CMV virus load was 1 410 000 copy/ml. CMV viral load at breast milk was 100 000 copy/ml. Eye examination for CMV retinitis was negative, and there was no pathology related to CMV in cranial USG. Because there was no organ involvement, no therapy was given. The patient was discharged at Day 69.
CASE REPORT
170
10. Wu HY, Huang SC, Huang HC, et al. Cytomegalovirus infection and fetal death in one monozygotic twin. Taiwan J Obstet Gynecol 2011;50:230–2. 11. Kitajima J, Inoue H, Ohga S, et al. Differential transmission and postnatal outcomes in triplets with intrauterine cytomegalovirus infection. Pediatr Dev Pathol 2012;15:151–5. 12. Ahlfors K, Ivarsson SA, Nilsson H. On the unpredictable development of congenital cytomegalovirus infection. A study in twins. Early Hum Dev 1988;18: 125–35. 13. Seguin J, Cho CT. Congenital cytomegalovirus infection in one monozygotic twin. JAMA 1988;260: 3277. 14. Baker ER, Eberhardt H, Brown ZA. ‘‘Stuck twin’’ syndrome associated with congenital cytomegalovirus infection. Am J Perinatol 1993;10:81–3. 15. Bataille H, Elgellab A, Toussaint P, et al. Twin pregnancy and congenital cytomegalovirus infection with different outcomes. Arch Pediatr 1998;5:1168. 16. Yinon Y, Yagel S, Tepperberg-Dikawa M, et al. Prenatal diagnosis and outcome of congenital cytomegalovirus infection in twin pregnancies. BJOG 2006;11:295–300.
Journal of Tropical Pediatrics
Vol. 60, No. 2
Downloaded from http://tropej.oxfordjournals.org/ at University of Notre Dame on August 22, 2014
3. Nigro G, Adler SP, La Torre R, et al. Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 2005;353:1350–62. 4. Pass RF, Fowler KB, Boppana SB, et al. Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome. J Clin Virol 2006;35:216–20. 5. Stagno S, Cloud GA. Working parents: the impact of day care and breast-feeding on cytomegalovirus infections in offspring. Proc Natl Acad Sci USA 1994; 91:2384–9. 6. Hamprecht K, Goelz R, Maschmann J. Breast milk and cytomegalovirus infection in preterm infants. Early Hum Dev 2005;81:989–96. 7. Chiavarini M, Bragetti P, Sensini A, et al. Breastfeeding and transmission of cytomegalovirus to preterm infants. Case report and kinetic of CMV-DNA in breast milk. Ital J Pediatr 2011;37:6. 8. Jim WT, Shu CH, Chiu NC, et al. Transmission of cytomegalovirus from mothers to preterm infants by breast milk. Pediatr Infect Dis J 2004;23:848–851. 9. Maschmann J, Hamprecht K, Dietz K, et al. Cytomegalovirus infection of extremely low-birth weight infants via breast milk. Clin Infect Dis 2001; 33:1998–2003.
![[Postnatal cytomegalovirus infection in preterm infants: the role of breast milk].](/assets/img/hold.png)
