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COCA Conference Call 2009 H1N1 Influenza
Pregnant Women and Newborns
Sonja A. Rasmussen, MD, MS Division of Birth
Defects and Developmental Disabilities Centers
for Disease Control and Prevention Wanda D.
Barfield, MD, MPH Division of Reproductive
Health Centers for Disease Control and
Prevention November 17, 2009
The findings and conclusions in this report are
those of the author and do not necessarily
represent the official position of the Centers
for Disease Control and Prevention.
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2009 H1N1 Influenza Pregnant Women and
Newborns Outline of Presentation

• Influenza and Pregnancy (Dr. Rasmussen)
• Testing and Treatment (Dr. Rasmussen)
• Vaccination (Dr. Rasmussen)
• Infection Control Guidance (Dr. Barfield)
• Influenza and the Newborn (Dr. Barfield)

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Pregnant Women at Increased Risk for Severe
Influenza Illness

• Changes in immune, respiratory and cardiovascular
  systems can result in pregnant women being more
  severely affected by certain viral pathogens
• Increased mortality from influenza during
  previous pandemics (1918 and 1957)
• Increased risk of complications related to
  seasonal influenza

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Risk of Hospital Admission for Respiratory
Illness during Influenza Season by Pregnancy
Status among Women with No Comorbidity,
Nova Scotia, 1990-2002
Compared to year before pregnancy
Dodds et al., CMAJ 176463-8, 2007
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Fetal Concerns regarding Influenza during
Pregnancy

• Effects of influenza on the fetus are unknown and
  difficult to predict
• In seasonal influenza, viremia is believed to
  occur infrequently and placental transmission
  appears to be rare may differ with novel
  influenza strains
• Fever is a risk factor for some types of birth
  defects and other adverse outcomes

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Novel Swine-Origin Influenza A (H1N1) Virus
Investigation Team, N Engl J Med 361, 2009
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2009 H1N1 Influenza

• Illness resulted from quadruple reassortment
  virus of human, avian and swine influenza virus
  genes
• Viruses susceptible to oseltamivir and zanamivir,
  resistant to amantadine and rimantadine
• Median age 20 years, range 3 months
  to 81 years 60 were 18 years or
  younger (based on 642 confirmed
  cases reported 4/15-5/5/2009)

Novel Swine-Origin Influenza A (H1N1) Virus
Investigation Team, N Engl J Med 361, 2009 CDC,
MMWR Morb Mortal Wkly Rep 58536-41, 2009 and
58497-500, 2009
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2009 H1N1 Influenza (continued)

• In the US, most confirmed cases characterized by
  self-limited, uncomplicated febrile respiratory
  illness similar to seasonal influenza (cough,
  sore throat, rhinorrhea, headache, and myalgia)
  38 with vomiting or diarrhea (based on 642
  confirmed cases reported 4/15-5/5/2009)

Novel Swine-Origin Influenza A (H1N1) Virus
Investigation Team, N Engl J Med 361, 2009 CDC,
MMWR Morb Mortal Wkly Rep 58536-41, 2009 and
58497-500, 2009
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Jamieson et al., Lancet 374451-8, 2009
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2009 H1N1 Influenza and
Pregnancy

• 34 confirmed or probable cases of 2009 H1N1
  influenza in pregnant women (April 15-May 18,
  2009) in US
• Infections in all three trimesters (9 1st, 56
  2nd, 26 3rd, 9 unknown)
• Manifestations similar to those seen in the
  general population
• 11 women (32) were admitted to hospital
• 6 deaths among pregnant woman with pandemic
  (H1N1) 2009 influenza (April 15-June 16, 2009)
  (6/45 or 13 of total)

Jamieson et al., Lancet 374451-8, 2009
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Admission Rates for Pregnant Women and General
Population with 2009 H1N1 InfluenzaUnited
States, April 15 to May 18, 2009
Population Admission Rate per 100,000 (95 CI)
Pregnant women 0.32 (0.13-0.52)
General Population 0.076 (0.07-0.09)
Risk Ratio 4.3, 95 CI 2.3-7.8
Jamieson DJ et al., Lancet 374451-8, 2009
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Deaths in Pregnant Women due to 2009 H1N1
Influenza United States, April 15 to June 16,
2009
Case Age (years) Weeks gestation Underlying Medical Conditions
1 33 35 Mild asthma, psoriasis
2 24 32 Obesity
3 20 27 None
4 21 11 Factor V Leiden deficiency
5 22 36 None
6 30 30 None
Jamieson DJ et al., Lancet 374451-8, 2009
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Additional Clinical Information on Deaths among
Pregnant Women

• All patients developed primary viral pneumonia
  with subsequent ARDS requiring mechanical
  ventilation
• Pregnancy outcomes 5 with cesarean delivery
  (27-36 weeks gestation 3 in ICU or ED), 1 fetal
  loss at 11 weeks
• Length of time from symptom onset to receipt of
  antiviral medication was 6-15 days (median 9)
• Length of time from presentation for medical care
  until receipt of antiviral treatment was 2-14
  days (median 4.5)

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Updated Information on Deaths among Pregnant Women

• 6 of deaths in US from pandemic (H1N1) 2009
  Influenza are among pregnant women (based on 484
  H1N1 deaths reported to CDC by August 21, 28 of
  whom were pregnant)
• Pregnant women 1 of the general population

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CDC Interim Guidelines

• Testing for 2009 H1N1 influenza
• Antiviral treatment and prophylaxis
• Seasonal and 2009 H1N1 influenza vaccination

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Influenza Diagnostic Testing
Test Method Time to Process Sensitivity for 2009 H1N1 Distinguishes 2009 H1N1?
Rapid influenza diagnostic tests Antigen detection 0.25 hour 10-70 No
Direct and indirect immunofluorescence assays (DFA/IFA) Antigen detection 2-4 hours 47-93 No
Nucleic acid amplification tests (e.g., rRT-PCR) RNA detection 48-96 hours 86-100 Yes
Virus isolation in tissue cell culture Virus isolation 2-10 days -- Yes
rRT-PCR real-time reverse transcriptase
polymerase chain reaction
http//www.cdc.gov/flu/professionals/diagnosis/080
9testingguide.htm www.cdc.gov/h1n1flu/guidance/ra
pid_testing.htm
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Testing and Treatment

• Treatment is recommended for pregnant women with
  suspected or confirmed influenza, regardless of
  trimester of pregnancy
• Treatment also recommended for women who are up
  to 2 weeks postpartum (including following
  pregnancy loss)
• Do not delay treatment because of a negative
  rapid influenza diagnostic test or inability to
  test or while awaiting test results

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Treatment

• Oseltamivir (Tamiflu)
• 75 mg po bid for 5 days
• BEST if started as soon as possible (i.e., within
  48 hours of symptom onset), but later treatment
  also of benefit
• Oseltamivir (Tamiflu) and zanamivir (Relenza)
  are FDA pregnancy category C
• Available data suggest not human teratogens
  Tanaka et al. CMAJ 18155-8, 2009
• Considering severity of disease, treatment
  benefit outweighs potential risk
• Acetaminophen for fever

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Treatment

• Rapid access to antiviral medications is
  essential
• Actions that might reduce delays in treatment
  initiation
• Informing pregnant women of signs and symptoms of
  influenza and need for early treatment
• Ensuring rapid access to telephone consultation
  and clinical evaluation
• Considering empiric treatment of patients at
  higher risk for influenza complications based on
  telephone contact

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Post-exposure Chemoprophylaxis

• Consider if close contact with suspected or
  confirmed case
• Zanamivir (Relenza) Two 5mg (10 mg) inhalations
  qd
• Oseltamivir (Tamiflu) 75 mg qd
• 10 day duration
• Close monitoring and early treatment is an
  alternative to chemoprophylaxis

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Post-exposure Chemoprophylaxis

• Close contact defined as having cared for or
  lived with a person who is a confirmed, probable,
  or suspected case of influenza, or having been in
  a setting where there was a high likelihood of
  contact with respiratory droplets and/or body
  fluids of such a person
• Examples
• sharing eating or drinking utensils
• physical examination

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ACIP Recommendations for Seasonal Flu Vaccination

• Because pregnant women are at increased risk for
  influenza complications, seasonal influenza
  vaccine is recommended for women who will be
  pregnant during influenza season
• This includes all pregnant women in any trimester

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Laboratory-Proven Influenza in Infants
WhoseMothers Received Influenza Vaccine vs
Controls
Zaman et al., N Engl J Med 3591555-64, 2008
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ACIP Recommendations for 2009 H1N1 Vaccination

• Pregnant women
• Household contacts and caregivers for children
  younger than 6 months of age
• Healthcare and emergency medical services
  personnel
• All people from 6 months through 24 years of age
• Persons aged 25 through 64 years who have health
  conditions associated with higher risk of
  influenza-related complications

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Need for 2009 H1N1 Vaccine

• Pregnant women who get 2009 H1N1 influenza at
  higher risk for hospitalization, severe illness
  and death
• Seasonal flu vaccine not expected to protect
  against 2009 H1N1 influenza

Jamieson DJ et al., Lancet 374451-8, 2009
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Vaccine Types

• Live attenuated vaccine (not licensed for use in
  pregnant women, but can be used postpartum)
• Multidose inactivated vaccine
• Prefilled single dose inactivated vaccine
  (preservative-free)

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Vaccine Administration

• Can be given at any time during pregnancy
• Can also be given postpartum, providing indirect
  protection for infants lt6 months
• Recommended even for women who have had suspected
  influenza
• Inactivated vaccines against seasonal flu and
  2009 H1N1 can be administered simultaneously (but
  use different anatomic sites)

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Safety of influenza vaccination during pregnancy

• 11 studies published between 1964 and 2008 about
  safety of seasonal influenza vaccination during
  pregnancy
• None identified maternal or fetal problems with
  influenza vaccination
• Safety of 2009 H1N1 vaccine is anticipated to be
  similar to seasonal flu vaccine

Tamma et al., Am J Obstet Gynecol 2009 Oct 20.
Epub ahead of print
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Considerations Regarding 2009 H1N1 in Intrapartum
and Postpartum Hospital Settings

• Newly revised guidance issued Nov. 12, 2009
• Applies to intrapartum and postpartum hospital
  settings for uncomplicated term deliveries
• Includes guidance upon discharge to home
• Incorporates feedback from relevant professional
  organizations
• Consistent with updated infection control
  guidance
• Considers current design and staffing of labor,
  delivery, recovery, and postpartum (LDRP) wards

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PRIOR Guidance

• Mother should consider avoiding close contact
  with infant until
• Antiviral medication for 48 hours
• Fever has fully resolved
• She can control coughs and secretions
• Before these conditions are met
• Newborn cared for in separate room by well
  caregiver
• Mother encouraged to pump breast milk
• Infant considered as potentially infected

Considerations Regarding Novel H1N1 in Obstetric
Settings (July 6, 2009)
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Feedback on Prior Guidance

• Solicited
• External experts in
• Infection Control
• Influenza
• Obstetrics and Gynecology
• Neonatology
• Pediatrics
• Human lactation
• Immunobiology
• American Academy of Pediatrics
• Committee on Fetus and Newborn
• Section on Perinatal Practices
• Section on Breastfeeding
• Academy of Breastfeeding Medicine
• International Lactation Consultant Association

• Received
• Feedback during COCA and other conference calls
• Feedback at professional meetings
• More than 90 emails/phone calls
• Pediatricians
• Lactation Consultants
• Epidemic Response Coordinators
• Medical Officers
• State Health Departments
• State Breastfeeding Coalitions
• Health Professional Associations

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Concerns Raised by Perinatal Experts

• Configuration and staffing of current LDRP and
  newborn nurseries and isolation protocols
• Limited evidence for infection of the fetus
• Separation of mother and infant and breastfeeding
  disruption
• Potential exposure of the newborn to other
  potentially infected individuals in the hospital
  and at home

Including AAP COFN and SoPPe, Oct 13 and 16
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Labor, Delivery, Recovery, Postpartum (LDRP)
Rooms
Newborn Isolette
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Modes of 2009 H1N1 Transmission Considerations
for the Fetus

• Placental Transmission
• For 2009 H1N1, no confirmed reports of placental
  transmission may possibly occur in severe
  maternal illness
• Gu et al. Lancet 2007
• Placental transmission of H5N1
• Maternal death from H5N1 in second trimester
• Viral infection of placenta, fetal tissues

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Modes of 2009 H1N1 Transmission Considerations
for the Newborn

• Postpartum Transmission
• Possible for the mother with influenza and fever
• Small particle aerosols from infectious mother to
  newborn in close vicinity
• Droplet exposure to newborn mucosal surfaces
• Inoculation of newborn mucosal surfaces by
  him/herself or caregivers

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Vulnerability of the Newborn

• Immature immune system
• Less protection from droplet infections
• Immunologic protection against respiratory
  infection via mothers milk
• In need of constant close contact
• Potential exposure to infected caregivers,
  healthcare providers, or siblings
• Not feasible to provide vaccine or
  chemoprophylaxis with antivirals

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Influenza-associated deaths among children in the
U.S., 2003-2004
Bhat et al. N Engl J Med 2005 353 2559-67
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Infection Control in Intrapartum and Postpartum
Hospital Settings General Considerations

• Keep newborns separated from ill caregivers and
  providers.
• Avoid transmission from infected infants to
  uninfected/critically ill infants (e.g. NICU).
• Include flexibility based on LDRP configuration.
• Assure the availability of mothers milk to the
  newborn.
• Provide guidance for discharge to home where
  newborn may be more vulnerable.

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NEW Guidance
Cautious approach, provides for flexibility based
on hospital configuration, staffing, and surge
capacity.

• Priority focus Minimizing infants risk of
  exposure to droplets
• Considers infant exposed rather than infected
• Provides two-step process for postpartum and
  newborn management
• Provides guidance for hospital discharge planning

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NEW Guidance

• Intrapartum (Labor/Delivery/Recovery)
• Place surgical mask on ill mother during labor
  delivery, if tolerable
• Treat mother with antiviral medication as soon as
  possible
• Temporarily separate mother and infant after
  delivery (gt6 feet)
• Bathe the infant early, consider infant exposed,
  not infected, unless otherwise clinically
  indicated

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NEW Guidance

• Postpartum
• Step 1 Temporary separation
• Place mother in single-patient room
• Newborn can accompany mother, if placed in
  isolette
• Other options
• Bassinette/curtain at gt 6 feet
• Newborn nursery with standard precautions, if
  well
• Consider isolation if suspected H1N1 infection

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NEW Guidance

• Postpartum (cont.)
• Infant is fed by healthy caregiver
• Encourage/support breastfeeding
• Assist mother to express milk
• Mother initiates contact and direct feeding
  after
• Afebrile for 24 hours
• Antivirals for 48 hours
• Coughs and secretions can be covered/controlled

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NEW Guidance

• Postpartum (cont.)
• Step 2 Continued precautions
• For 7 days after symptom onset and symptom-free
  for 24 hours, mother should
• Adhere to strict hand hygiene
• Wear a face mask
• Use respiratory hygiene and cough etiquette
• Limit visitors to healthy persons necessary for
  patients emotional well-being and care

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NEW Guidance

• Newborn Care
• Consider infant exposed, not infected, unless
  otherwise clinically indicated
• Prophylactic use of antivirals in infants lt 3
  months is not recommended
• Antiviral treatment in cases of suspected
  infection is authorized under FDA emergency use
  authorization for infants lt 1 year
• Oseltamivir 3 mg/kg/dose bid

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NEW Guidance

• Discharge Planning
• Instruct family on newborn care at home
• Strict hand hygiene, cough etiquette
• Limit ill contacts to newborn
• Instruct caregivers to obtain H1N1 vaccine
• Family members
• Daycare providers
• Siblings
• Educate on signs and symptoms of infant infection
  and steps to take if any are observed

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Additional CDC Resources

• http//www.cdc.gov/H1N1flu/clinician_pregnant.htm
• http//www.cdc.gov/h1n1flu/pregnant
• http//www.cdc.gov/h1n1flu/guidelines_infection_co
  ntrol.htm

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Conclusions

• Based on the experience with previous pandemics
  and with seasonal influenza, pregnant women are
  expected to be a high-risk population in an
  influenza pandemic
• Available data suggest that pregnant women are at
  increased risk for complications and death from
  2009 H1N1 influenza

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Conclusions

• Pregnant women and women up to 2 weeks postpartum
  should be informed about the signs and symptoms
  of 2009 H1N1 influenza
• Pregnant women and women up to 2 weeks postpartum
  who present with suspected influenza should be
  treated empirically with oseltamivir
• Post-exposure prophylaxis with zanamivir or
  oseltamivir can be considered for pregnant women
  and women up to 2 weeks postpartum

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Conclusions

• Both seasonal and 2009 H1N1 influenza vaccines
  recommended for pregnant women
• 2009 H1N1 vaccine safety expected to be similar
  to seasonal influenza vaccine

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Conclusions

• If a mother has suspected/confirmed 2009 H1N1
  infection during labor/delivery, important steps
  can be taken in the hospital to protect the
  newborn from infection
• Step 1 Temporarily separate mother and newborn
  in order to prevent droplet transmission to the
  newborn when the mother is most infectious
• Step 2 Implement precautions for mother and
  other household contacts to prevent droplet
  transmission to the infant

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Conclusions

• Mothers with suspected/confirmed H1N1 should be
  encouraged and supported to provide breast milk
  and later breastfeed
• Upon hospital discharge, counsel families on ways
  to protect the newborn against H1N1 infection in
  the home
• Vaccinating pregnant women and caregivers of
  infants lt 6 months of age is the best prevention
  strategy against 2009 H1N1 infection

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Thank you!
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