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TIPQC – 2011

Robert M. Lawrence, MD
University of Florida Shands Children’s Hospital
Faculty Disclosure
Information
In the past 12 months, I have no relevant
financial relationships with the
manufacturer(s) of any commercial product(s)
and/or provider(s) of commercial services
discussed in this CME activity.

I do not intend to discuss an


unapproved/investigative use of a
commercial product/device in my
presentation.
 Evidence of  No clear-cut evidence of
Transmission Transmission
 HIV-1, HIV-2  Hepatitis B or C
 HTLV I, II  Rubella
 Varicella
 CMV
 Dengue virus
 West Nile Virus (PCR)  Human Papillomavirus
(DNA)
 Herpes Simplex Virus
 Human Herpes Virus 6, 7
Lawrence RM, Lawrence RA.  Enteroviruses
Breast milk and infection.  Rabies
Clin Perinatol 2004, 31:501-528.
 Estimated risk of vertical transmission - with or
without breastfeeding
 Dose –response relationship for viral load and risk of
transmission
 HIV DNA detectable in BM, isolating live HIV is more
difficult, cell-free and cell-associated virus
 Metanalysis of 5 reports estimated risk of
transmission due to BF alone at 14% ( CI 7-22%)
 Analysis of benefit of BF against infant mortality due
to other illnesses in specific communities and
countries
 In U.S. – HIV Positive mothers - no breastfeeding is
recommended
King SM and Committee on Pediatric AIDS. Evaluation and Treatment of
the HIV-1 Exposed Infant. Pediatrics 2004, 114:497-505.
• Duration of breastfeeding
• Dose-response relationship = maternal viral
load in plasma or breast milk and duration of
BF
• Maternal illness or lower CD4 counts
• Breast abnormalities – mastitis or nipple
lesions
• Mixed breastfeeding versus exclusive
breastfeeding
 Kenya – improved HIV-1-free survival in formula feed
infants, but similar mortality (24.4% BF versus 20% FF)
and similar incidence of diarrhea and pneumonia over
the first two years of life. (Mbori-Ngacha D et al.
JAMA, 2001)
 Malawi – BF HIV-exposed infants had lower mortality
at 24 months of age than the FF HIV-exposed infants.
BF was exclusive for 2 months and mixed after that.
(Taha T et al. Bulletin WHO, 2006)
 Botswana – decreased risk of HIV infection with FF,
but increased cumulative mortality for FF infants at 7
months of age. ( Thior I et al. JAMA, 2006)
• Cote d’Ivoire – exclusive BF for 4 months versus
FF with no difference in HIV infection over 2
years. (Becquet R et al. PLoS Med, 2007)
• South Africa – exclusive BF for 6 months,
increased risk of HIV infection with mixed feeds
and increased mortality at 3 months of age for
mixed fed infants (15%) compared with
exclusively BF infants (6.1%). (Coovadia HM et
al. Lancet, 2007)
 Lower viral loads in BM of mothers receiving ARV therapy but
not absent (virus still in infected cells) (Shapiro RL et al. JID,
2005; Giuliano M et al. JAIDS, 2007)
 All mothers received HAART with cumulative incidence of HIV
at 6 months – 2.7% for FF (809 mother-infant pairs) and 2.2%
for exclusively BF infants (251 mother-infant pairs). (Palombi
L et al. AIDS, 2007)
 Tanzania – maternal HAART plus exclusive BF and “abrupt”
weaning at 5-6 months demonstrated HIV transmission of
4.1% at 6 weeks, 5% at 6 months and 6.0% at 18 months of
age. The cumulative risk of HIV transmission was only 1.1%
between 6-18 months of age. (Kilewo C et al. JAIDS, 2009)
 Sub-Saharan Africa – 6 months of maternal HAART and 6
months of exclusive breastfeeding demonstrated 94% HIV-
free survival at 12 months of age and lower maternal and
infant mortality. (Marazzi MC et al. PIDJ, 2009)
 Cote d’Ivoire – limiting BF to only 4 months
and short course ARV therapy for the infant
each decreased HIV transmission through 18
months of age. (Leroy V et al. PLoS ONE,
2008)
 Tanzania – BF for 18 weeks with ARV – sdNVP
+ 3TC for 1 week + 3TC alone for 6 months
versus only 1 week of ZDV + 3TC showed 50%
less HIV transmission. (Kumwenda N et al.
NEJM, 2008)
 How to enhance protection from BM - antibodies,
cytokines, nucleotides, glycosaminoglycans, other
inhibitory factors?
 What is the optimal duration of exclusive
breastfeeding, the appropriate timing of rapid
weaning and transition to alternative feeding with
adequate nutritional support?
 How to perform carefully controlled research on
maternal ARV / HAART therapy in preventing HIV
transmission via BM and optimizing the infants’
nutrition and growth?
 How to compare ARV prophylaxis for the infant to
Maternal ARV therapy in HIV transmission
prevention?
 How to reach the goal of 100% prevention of HIV
transmission from mother-to child?
 Identify Active TB versus latent TB infection (LTBI)
 TB symptoms, Chest x-ray, TST, smear + culture
 Maternal TB status should be determined prior to
delivery
 Congenital TB is very rare
 TB mastitis is a contraindication to use of breast milk
 Respiratory droplet nuclei is the risk! (not breast milk)
 Mother with active TB – isolate, evaluate, begin
empiric treatment, pump milk – give to the infant
 Consider empiric Isoniazid for the infant
 Look for active TB in the household
• Vertical transmission of HTLV I (from any mode
of transmission) is documented at 1-5% in
different reports
• Estimated that 1 ml of BM contains 1000
infected T cells
• Studies on transmission show that breastfed
infants have ~30% transmission rate, mixed-fed
infants ~ 10% and formula fed = 0%
• Increased risk with duration of BF > 6 months
• HTLV I and II are rare in the US – confirm testing
• Consider advising against BF and provide an
alternative source of infant nutrition
 Premature and VLBW infants
 Virolactia and BF, 17/29 (59%) showed CMV
transmission versus 0/27 when CMV was
not detected in the milk
 Peak of virolactia at 3-4 weeks post-partum
 5/17 infants were infected before 2 months
of age and developed a “sepsis-like” illness.
 In 12/17 infants infected after 2 months of
age, 5/12 developed mild signs of illness.

Vochem M et al. Pediatric Infect Disease Journal 17:53, 1998.


 Intermittent reactivation and excretion of the CMV virus
 CMV is readily isolated from urine, saliva, tears, semen,
cervical secretions and human milk
 CMV isolation from colostrum is lower than from mature
human milk, but not zero. (Hayes K et al. NEJM, 1972;
Stagno S et al. PNAS, 1994)
 CMV remains latent in CD34+ cells in the bone marrow
and perhaps in renal epithelial cells and salivary glands.
 Vochem M et al, reported increased CMV virolactia at 3-4
weeks post-partum. ( Peds Inf Dis J, 1998)
 Yaeger AS et al, demonstrated significant CMV virolactia
between 2 and 12 weeks post-partum. (J Pediatr, 1983)
 Preterm delivery < 32 weeks
 Screen the mother for CMV serology at delivery
 Feedings can start with maternal BM /
colostrum for 1st 7 days
 If CMV IgG positive freeze BM for 24 -72 hrs
then give thawed, until infant >32 weeks or
use pasteurized banked BM
 If mother CMV negative use fresh or frozen–
thawed BM
 Observe infants < 32 weeks for S + S of CMV
(severe respiratory deterioration,
thrombocytopenia, leukopenia, hepatitis)
Wight NE, 2/2005. Recommendations for Minimizing CMV
Exposure in Breast-milk fed VLBW Preterm Infants.
 Pasteurization
Heat at 62.50C for 30 minutes
Effective inactivation of CMV
Damages Immunoglobulins (Igs) + lymphocytes
 Freezing
-200C for greater than 3 days
Less effective at inactivating CMV
Apparentlty less harmful to cells and Igs
 Rapid high temperature
720C for 5-10 seconds
undergoing further study
 No prospective, controlled trials documenting the
protective effect of such methods.
 prove the occurrence of a specific infection in the
mother and persistence of the infectious agent
such that it could be transmitted to the infant
 isolate/identify the infectious agent in colostrum,
breast milk or in a breast lesion
 document a reasonable mechanism of
transmission through breastfeeding or breast milk
 demonstrate clinical and laboratory evidence of a
significant infection in the infant
 exclude other possible mechanisms of
transmission
 Risk in breastfed vs. formula fed infants
 Protection vs. risk due to breast milk
 Timing of the maternal infection
 Risk of infection due to other mechanisms
of transmission
 Duration of breastfeeding
 Breastfeeding definitions - exclusive,
partial, token, none
 Susceptibility of infant
 Hepatitis A, B or C - history, risk, vaccine
 Exposure to TB, Tuberculosis status
 Rash or viral illness since LMP
 History of sexual transmitted disease (STD), GC,
Chlamydia, HPV, Syphilis, HSV, HIV
 “Childhood illnesses” - Rubella, Measles,
Varicella-Zoster virus
 Other: CMV, HTLV I or II, GBS, MRSA
 HIV exposure and testing
 Consider the site of infection, probable organisms
involved, possible mechanisms of transmission,
virulence of infectious agents, likely susceptibility of
the infant
 If indicated, empiric therapy for the mother with
medications compatible with breastfeeding
 Evaluate the infant / continued observation for
illness / consider empiric or preventive therapy for
the infant
 Decisions re:
isolation of mother
separation of infant from the mother
continue breastfeeding
utilizing expressed breast milk
maintain the milk supply
Alfin2100.blogspot.com/2006_01_01_archive.html
 HBsAg identified in breast milk, but
transmission by BF is not well documented
 No difference in vertical transmission rates for
BF and non-breastfed infants
 Risk of Chronic Hepatitis B infection after
perinatal infection = 90%
 Protection afforded by HBIG and HBV vaccine is
greater than 95%
 The risk is not zero - discuss with parents
 Anti-HCV Ab and HCV-RNA identified in
colostrum and breastmilk
 HCV-RNA levels in BM do not correlate with
HCV-RNA titers in maternal serum
 Risk of chronic infection after perinatal
infection 70-85%
 Published transmission rates from HIV
negative mothers ranges from 0-42%
 Transmission rates similar breast-fed and
formula fed infants - studies poorly controlled
HCV-RNA titers in maternal serum
HCV-RNA titers in BM
amount of BF
duration of BF
 Increased risk - HIV co-infection, HCV
genotype, active maternal liver disease, and
elevated maternal HCV-RNA serum titers, (no
data re: blood in BM)
 Discuss risks with mother / parents
 General rate of Perinatal HSV infection is
1:2000 - 5000 live births
 Primary HSV infection > risk than recurrent
 Prematurity and HSV-2 pose greater risk for
perinatal HSV infection
 BF is OK if there are no breast lesions
 Cover lesions, careful hand washing, with or
without maternal antiviral treatment
 Culture infant if in the perinatal period
otherwise only if clinically indicated
 Prophylactic therapy for the infant?
 Multiple case reports and summary
 Early vs. late-onset GBS infection
 Premature infants greater risk
 Colonization “exchange”
 Maternal mastitis or not
 Universal prenatal GBS screening
 Culturing BM

Byrne PA, Miller C, Justus K. Neonatal GBS Infection Related to Breast Milk
Breastfeeding Medicine 1(4):263-70, 2006
1. Follow CDC Guidelines for GBS screening
2. Review proper hygiene for milk expression
3. Procedures for collection / storage – The
Human Milk Banking Assoc of N.A. , 1993.
4. Infant ill in SCN – culture the milk, consider
withholding milk, observe the mom for illness
5. If mastitis or plugged ducts – hold BM, culture
milk and observe the infant closely
6. Provide banked milk until BM cultures –
negative
7. Support pumping for milk supply
8. Decide re: antibiotic therapy Byrne PA, et al.
BFMed 1(4):263-70, 2006
 Midstream expressed milk
 Sterile container, immediate transport to lab
 Store at 40 C
 Quantitative cultures – blood + MacConkey agar
 Viral cultures require viral media or transport
material and notification of lab
 Identify all species other than skin commensals
 Report with quantification
 Sensitivity testing for possible pathogens
 Surveillance or routine cultures not useful in
general (exceptions – “outbreaks” or in NICU)
 Contamination – widely reported
 Interpretation – significant quantity - greater
than 104 or 105 bacteria, pathologic vs.
opportunistic organisms
 Interpretation of viral cultures – timing and
negative tests
 Different “cutoffs” for full term vs. preterm?
 Many reports concerning pustulosis in full term
infants
 Risk reported for circumcision, preterm infants
not BF
 Carriers
 Community-acquired MRSA (CA MRSA)
 MSSA
 Colonization – nares, rectum, skin
 Eradicating colonization
 Contact is the usual transmission mechanism
not BM
 Review proper hygiene for milk expression
and proper technique for BF
 Procedures for collection / storage – The
Human Milk Banking Assoc of N.A. , 1993.
 Infant ill in SCN – culture the milk, consider
withholding milk, observe the mom for illness
 If mastitis or plugged ducts – hold BM
temporarily and maintain supply, culture milk
and treat mother empirically if indicated
 Observe the infant closely
 Provide banked milk until BM cultures –
negative
 Support pumping for milk supply
 Decide re: antibiotic therapy
 Lawrence RA, Lawrence RM. Breastfeeding: A Guide for
the Medical Professional. 7th ed. Elsevier Mosby, New
York, 2010
 Lawrence RM, Pane CA. Human Breast Milk: Current
Concepts of Immunology and Infectious Diseases.
Curr Probl Pediatr and Adolesc Health Care 2007,
37(1):1-37.
 Henig MJ. Host defense benefits of breastfeeding for
the infant. Pediatr Clin North Amer 2001, 48(1):105-
23.
 Kramer MS, Kakuma R. The optimal duration of
exclusive breastfeeding: a systemic review. Adv Exp
Med Biol 2004, 554:63-77.
 Lawrence RM, Lawrence RA. Breast milk and infection.
Clin Perinatol 2004, 31:501-528.
 Breastfeeding and H1N1 Influenza A - Academy of BF Medicine
http://www.bfmed.org/Media/Files/Documents/H1N1%20and%2
0Breastfeeding%20-%20for%20physicians1.pdf
 2009 H1N1 Flu and Feeding your Baby – CDCP
http://www.cdc.gov/h1n1flu/infantfeeding.htm
 Recommendations for Minimizing CMV Exposure in Breastmilk-
fed VLBW Preterm Infants. Wight NE. 2005
http://www.breastfeeding.org/pdf/CMVPREMI-2005.pdf
 Transmission of WNV through human breast milk seems to be
rare. Hinckley AF et al, Pediatrics 2007;119(3):e666-671.
 CDCP. Possible WNV transmission to an infant through
breastfeeding. MMWR 2002, 51(39):877-8.
 Taha T et al. The impact of BF on the health of HIV-positive
mothers and their children in subSaharan Africa. Bulletin WHO
2006;84:546.
 Thior I et al. Breastfeeding plus infant Zidovudine prophylaxis for
6 months vs formula feeding plus infant zidovudine for 1 month
to reduce MTCT HIV in Botswana: the Mashi Study. JAMA
2006;296(7):794.
 Coovadia HM et al. MTCT of HIV-1 infection during exclusive BF
in the first 6 months of life: an intervention cohort study. Lancet
2007;369:1107.
 Leroy V et al. 18 –month effectiveness of short-course ARV
regimens combined with alternatives to breastfeeding to prevent
HIV MTCT. PLoS ONE 2008;3(2):e1645.
 Kumwenda N et al. Extended AARV Prophylaxis to reduce Breast-
milk HIV-1 Transmission. NEJM 2008;359:119.
 Kilewo C et al. Prevention of MTCT of HIV-1 through
Breastfeeding by treating Infants Prophylactically with Lamivudine
in Dar es Salaam, Tanzania. JAIDS 2009;48(3):315.
 Becquet R et al. Two-year morbidity-mortality and alternatives to
porlonged breast-feeding among children born to HIV-infected
mothers in Cote d’Ivoire. PLoS Med 2007;4(1):e17.
 Mbori-Ngacha D et al. Morbidity and mortality in breastfed and
formula-fed infants of HIV-1 infected women: A randomized
clinical trial. JAMA 2001;286:2413.
 King SM and Committee on Pediatric AIDS. Evaluation and
Treatment of the HIV-1 Exposed Infant. Pediatrics 204,
114:497-505.
 Shapiro RL et al. Highly active ARV therapy started during
pregnancy or postpartum suppresses HIV-1RNA, but not DNA in
breast milk. JID 2005;192:713-9. Epub 2005 Jul 27.
 Palombi L et al. Treatment acceleration program and the
experience of the DREAM program in prevention of MTCT of HIV.
AIDS 2007;21(Suppl 4):S65-71.
 Marazzi MC et al. Increased infant HIV-1 free survival at one year
of age in sub-saharan Africa with maternal use of ARV during BF.
PIDJ 2009;28:483.
Thoughts?
Comments?
Questions?
Discussion?

Thank you.