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Breast milk causing neonatal sepsis and death

  • J. Widger
    Correspondence
    Corresponding author: J. Widger, The Royal Children's Hospital, Flemington road, Parkville VIC 3052. Australia
    Affiliations
    Department of Neonatology, Limerick, Ireland
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  • Author Footnotes
    † Limerick Regional Hospital, Limerick, Ireland.
    N.H. O’Connell
    Footnotes
    † Limerick Regional Hospital, Limerick, Ireland.
    Affiliations
    Department of Microbiology, Midwestern Regional Hospitals, Limerick, Ireland
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  • Author Footnotes
    ‡ Limerick Regional Maternity Hospital, Limerick, Ireland.
    T. Stack
    Footnotes
    ‡ Limerick Regional Maternity Hospital, Limerick, Ireland.
    Affiliations
    Department of Neonatology, Limerick, Ireland
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  • Author Footnotes
    † Limerick Regional Hospital, Limerick, Ireland.
    ‡ Limerick Regional Maternity Hospital, Limerick, Ireland.

      Abstract

      Breast milk can occasionally transmit serious viral and bacterial infections to preterm infants. We present three cases of late-onset neonatal sepsis, including one that resulted in death, occurring in preterm infants. The likely source of the microorganisms in all three cases was expressed breast milk.

      Keywords

      The advantages of human breast milk as compared with formula in preventing neonatal sepsis and necrotizing enterocolitis have been well established; hence its widespread use in preterm infants [
      • Hylander MA
      • Strobino DM
      • Dhanireddy R
      Human milk feedings and infection among very low birth weight infants.
      ,
      • Chen A
      • Rogan WJ
      Breastfeeding and the risk of neonatal death in the United States.
      ,
      • Hanson LA
      • Korotkova M
      The role of breast feeding in prevention of neonatal infection.
      ]. However, breast milk can occasionally transmit serious viral and bacterial diseases to the neonate. Documented cases of infection with group B streptococcus [
      • Kotiw M
      • Zhang GW
      • Daggard G
      • Reiss-Levy E
      • Tapsall JW
      • Numa A
      Late-onset and recurrent neonatal Group B streptococcal disease associated with breast milk transmission.
      ], Listeria species [
      • Svabic-Vlahovic M
      • Pantic D
      • Pavicic M
      • Bryner AH
      Transmission of Listeria monocytogenes from mother's milk to her babies and to puppies.
      ], methicillin-resistant Staphylococcus aureus [
      • Gastelum DT
      • Dassey D
      • Mascola L
      • Yasuda LM
      Transmission of community associated methicillin resistant Staphylococcus aureus from breast milk in the neonatal intensive care unit.
      ], Salmonella species [
      • Qutaishat S
      • Stemper M
      • Spencer S
      • et al.
      Transmission of Salmonella enterica serotype Typhimurium DT104 to infants through mother's breast milk.
      ] and Mycobacterium tuberculosis [
      • Pronczuk J
      • Akre J
      • Moy G
      • Vallenas C
      Global perspectives in breast milk contamination: infectious and toxic hazards.
      ] report that the infection has been transmitted by this route. We report three cases of late-onset neonatal septicaemia in our unit, including one that resulted in death, which were likely to have been caused by contaminated expressed breast milk (EBM).
      Two cases involved twins who were delivered via emergency caesarean section at 32 weeks of gestation, following an in vitro fertilization pregnancy. There was prolonged rupture of membranes for 16 days, and antenatal steroids were given. Twin II, a female, was born with Apgar scores of 7 at 1 min and 9 at 5 min.
      She weighed 1.02 kg. She had mild respiratory distress syndrome and was admitted to the neonatal intensive-care unit. She received 48 h of continuous nasal positive airway pressure, and intravenous benzylpenicillin and gentamicin. After initial total parenteral nutrition, feeding with EBM was commenced on day 5. The baby was on enteral feeds with mother's EBM by day 9.
      On day 14, she developed a pyrexia of 37.5°C. Blood cultures were performed, and intravenous treatment with teicoplanin and gentamicin was commenced. Feeding was discontinued and she was started on intravenous fluids. Her condition gradually deteriorated. She was electively intubated and ventilated. Intravenous treatment with meropenem and ionotropic support was commenced. An echocardiogram revealed poor contractility, and cranial ultrasound revealed a left-sided grade 3 intraventricular haemorrhage. Blood cultures became positive after 20 h, with Gram-negative bacilli. On day 16 of life, the baby's neurological condition continued to deteriorate. Care was withdrawn with parental consent, and the baby died. The causative organism was identified as Escherichia coli. A bag urine specimen obtained on day 14 showed <10 leukocytes/μL, and E. coli was cultured. Cerebrospinal fluid obtained post-mortem showed scanty Gram-negative bacilli upon microscopy.
      Twin 1, a male, was born with Apgar scores of 8 at 1 min and 9 at 5 min. His birthweight was 1.39 kg. He received 48 h of benzylpenicillin and gentamicin, and required nasal positive airway pressure for respiratory distress syndrome for 4 days. Enteral feeds with mother's EBM were commenced on day 3. He remained well until day 15, when he developed a pyrexia of 37.4°C. Treatment with intravenous gentamicin, meropenem and teicoplanin was commenced, and EBM was discontinued. His blood cultures became positive at 11 h, with Gram-negative bacilli; however, he remained stable. A lumbar puncture, after 5 days of antibiotic treatment, was unremarkable. Antibiotics were continued for 10 days. He remained well, and was discharged with a normal examination on day 54.
      E. coli isolates from both twins’ blood and maternal EBM revealed indistinguishable strains upon molecular typing using pulsed-field gel electrophoresis (Fig. 1). There were no other cases of E. coli infection in the unit during this period.
      Figure thumbnail gr1
      FIG. 1PFGE of XbaI DNA digests showing indistinguishable banding patterns. Lane M - molecular marker, Lane A - Twin 1, Lane B - Twin 2, Lane C - Mother.
      The third case, which occurred 2 years previously, was a singleton female born by emergency caesarean section at 25 weeks of gestation. Her birthweight was 790 g. Her Apgar scores were 7 at 1 min and 8 at 5 min, and she was intubated from birth. Empirical treatment with intravenous penicillin and gentamicin was commenced, and continued for 10 days. On day 19, following initial total parenteral nutrition, maternal EBM was commenced. On day 21, the baby became clinically septic. Empirical treatment with cefotaxime and gentamicin was commenced. Blood cultures subsequently yielded Klebsiella pneumoniae. Owing to ongoing clinical sepsis, repeat blood cultures were obtained on day 26 that yielded K. pneumoniae again. Antimicrobial treatment was modified to meropenem, which was continued for 10 days. The baby subsequently made a full recovery. The mother's EBM was sent for culture, and also yielded K. pneumoniae, with an identical antibiogram. However, molecular typing was not undertaken at that time. There were no other episodes of K. pneumoniae sepsis in the unit during the same period.
      There have been previous reports of contaminated breast milk causing fatality in the neonate, but these have been associated with concurrent mastitis [
      • Kotiw M
      • Zhang GW
      • Daggard G
      • Reiss-Levy E
      • Tapsall JW
      • Numa A
      Late-onset and recurrent neonatal Group B streptococcal disease associated with breast milk transmission.
      ,
      • Gastelum DT
      • Dassey D
      • Mascola L
      • Yasuda LM
      Transmission of community associated methicillin resistant Staphylococcus aureus from breast milk in the neonatal intensive care unit.
      ]. However, in our series, neither mother had mastitis. Unlike for human donor milk, pasteurization and screening of milk from the infant's biological mother is not uniformly recommended [

      Red Book 2006. Report of the Committee on Infectious Disease, 27th edn. P127. American Academy of Pediatrics. EIK Grove Village.

      ]. The immunoprotective constituents of human milk are, however, stable after pasteurization at 56°C for 30 min [
      • Lawrence RA
      Storage of human milk and the influence of procedures on immunological components of human milk.
      ].
      Late-onset neonatal sepsis is classically acquired from the care-giving environment. We believe that the cause of sepsis in these babies was contaminated maternal breast milk. In the twins’ cases, the babies were being nursed in different rooms within the unit, staffed by separate midwives, making cross-contamination unlikely. Anecdotally, Gram-negative sepsis is uncommon in this unit. Both mothers were giving their own EBM. We follow standard guidelines for collecting, handling and storing breast milk [
      • UK Association for Milk Banking
      ]. Fresh EBM is stored in a refrigerator at 2–4°C for a maximum of 48 h. Otherwise, milk is frozen at –20°C for a maximum of 3 months. It is not current practice to routinely screen breast milk.
      It would be impossible to attribute with certainty the septicaemia in these infants to contaminated breast milk. We cannot rule out the possibility of sepsis arising endogenously in the infants as a result of colonization via direct handling by the mother. However, infection control measures with regard to parental handling of infants are strictly adhered to in the unit. We acknowledge that the vast majority of infants fed with EBM do not encounter any problems, despite being exposed to bacteria in breast milk [
      • Ajusi JD
      • Onyango FE
      • Muatanda LN
      • Wamola
      Bacteriology of unheated breast milk stored at room temperature.
      ].
      Further research is required to define what constitutes significant microbial contamination of breast milk. Strict hygiene procedures should be observed during breast milk expression. Routine screening and pasteurization of breast milk administered to preterm infants should be considered. We suggest that, in cases of unexplained late-onset or recurrent neonatal sepsis, or concurrent sepsis in siblings, EBM should be considered as a possible source of infection.

      Transparency Declaration

      There was no funding for this project. T. Stack has received a research grant from SMA in the past. The other authors have no conflict of interest to declare.

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