COCA Conference Call –
National Obstetric Grand Rounds:
Pandemic (H1N1) 2009 Influenza
and Pregnancy
Denise J. Jamieson, MD MPH
Division of Reproductive Health
Centers for Disease Control and Prevention
Sonja A. Rasmussen, MD, MS
National Center on Birth Defects and Developmental Disabilities
Centers for Disease Control and Prevention
Kevin Ault, MD
Department of Gynecology & Obstetrics
Emory University School of Medicine
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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National Obstetric Grand Rounds:
Pandemic (H1N1) 2009 Influenza and
Pregnancy
•Overview of influenza (Dr. Jamieson)
•Infection Control Guidance (Dr. Jamieson)
•Testing and Treatment (Dr. Rasmussen)
•Vaccination (Dr. Rasmussen)
•The Atlanta Experience (Dr. Ault)
Pregnant women at increased risk for
severe influenza illness
• No evidence that they are more
susceptible
• Increased mortality from influenza
during previous pandemics (1918 &
1957)
• Increased risk of complications
related to seasonal influenza
Risk of Hospital Admission for Respiratory Illness
during Influenza Season by Pregnancy Status*
among Women with No Comorbidity,
Nova Scotia, 1990-2002
Rate Ratios
8
6
5.1
4
2
2.1
1.7
0
1st trimester
2nd trimester
3rd trimester
*Compared to year before pregnancy
Dodds et al., CMAJ 176:463-8, 2007
Why are pregnant women at increased
risk for severe influenza illness?
• Mechanical, hormonal, immunologic alterations in
pregnancy
• Changes in respiratory and cardiovascular
systems - increased heart rate, stroke volume, and
oxygen consumption; decreased lung volumes
• Immunologic changes – shift away from cellmediated immunity
• These changes render pregnant women more
susceptible and more severely affected by certain
viral pathogens
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
• Hyperthermia is a risk factor for some
types of birth defects and other adverse
outcomes
Special Health Care Delivery Challenges
for Pregnant Women
• Guidelines regarding nonpharmaceutical
interventions might present special
challenges
• Pregnant women will require health care
access (prenatal care and delivery services)
• Pregnant women might be reluctant to
comply with recommendations because of
concerns about fetus
Influenza Vaccination Coverage among
Data from National Health Interview Survey
Recommended
Adult Populations, National
Health Interview Survey, 1989-2005
Lu et al., Vaccine 26:1786-93, 2008
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, N Engl J Med 361, 2009
Pandemic (H1N1) 2009
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 58:536-41, 2009 and 58:497-500, 2009
Pandemic (H1N1) 2009
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 4/155/5/2009)
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, N Engl J Med 361, 2009
CDC, MMWR Morb Mortal Wkly Rep 58:536-41, 2009 and 58:497-500, 2009
Jamieson DJ et al., Lancet 374:451-8, 2009
Pandemic (H1N1) 2009
Influenza and Pregnancy
• 34 confirmed or probable cases of
pandemic (H1N1) 2009 influenza in pregnant
women (April 15-May 18, 2009) in US
(34/5469 or 0.62% of total)
• 11 women (32%) were admitted to hospital
• 6 deaths among pregnant woman with
pandemic (H1N1) 2009 influenza (April 15June 16, 2009) (6/45 or 13% of total)
Jamieson DJ et al., Lancet 374:451-8, 2009
Presenting Manifestations in Pregnant
Women with Pandemic (H1N1) 2009
Influenza
United States, April 15 to May 18, 2009
Presenting manifestations
Fever
Cough
Rhinorrhea
Sore throat
Headache
Shortness of breath
Vomiting
Diarrhea
Jamieson DJ et al., Lancet 374:451-8, 2009
N (%)
33 (97%)
32 (94%)
20 (59%)
17 (50%)
16 (47%)
14 (41%)
6 (18%)
4 (12%)
Pregnancy Trimester at Time of
Pandemic (H1N1) 2009
Influenza Infection
United States, April 15-May 18, 2009
56
60
Percent
50
40
26
30
20
10
9
9
0
1st
trimester
2nd
trimester
3rd
trimester
Unknown
Trimester of Pregnancy
Jamieson DJ et al., Lancet 374:451-8, 2009
Admission Rates for Pregnant Women
and General Population with
Pandemic (H1N1) 2009 Influenza
United 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 374:451-8, 2009
Deaths in Pregnant Women due to
Pandemic (H1N1) 2009 Influenza
United States, April 15 to June 16, 2009
Case
Age
Weeks’
Underlying Medical
#
(years) gestation
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 374:451-8, 2009
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)
Updated Information on Deaths
among Pregnant Women
• ~ 5% of deaths in US from pandemic
(H1N1) 2009 Influenza are among
pregnant women (based on 484 H1N1
deaths reported to CDC by August 20,
24 of whom were pregnant)
• Pregnant women ~1% of the general
population
Infection Control in Obstetric Settings:
General Principles
• Keep pregnant outpatients and
inpatients separated from ill and
potentially ill patients
• Requires system for rapidly
assessing influenza-like
symptoms and triaging patients
Considerations regarding novel H1N1
in obstetric settings (July 6, 2009)
• Place surgical mask on ill mother during labor &
delivery, if tolerable
• Mother should consider avoiding close contact with
infant until:
– antiviral medication for 48 hours
– fever has fully resolved
– she can control coughs and secretions
• When in contact with the infant, mother should do
following until 7 days after symptom onset and
symptom-free for 24 hours:
– wear a facemask
– change to clean gown or clothing
– adhere to strict hand hygiene and cough etiquette
CDC Interim Guidelines
• Testing for 2009 H1N1 influenza
• Antiviral treatment and prophylaxis
• Seasonal and 2009 H1N1 influenza
vaccination
Influenza Diagnostic Testing
Sensitivity
Distinguishes
for 2009
2009 H1N1?
H1N1
Method
Time to
Process
Antigen
detection
0.25
hour
10-70%
No
Direct and indirect
Antigen
immunofluorescence
detection
assays (DFA/IFA)
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
Test
Rapid influenza
diagnostic tests
*rRT-PCR – real-time reverse transcriptase polymerase chain reaction
http://www.cdc.gov/flu/professionals/diagnosis/0809testingguide.htm
www.cdc.gov/h1n1flu/guidance/rapid_testing.htm
Testing and Treatment
• Treatment is recommended for
pregnant women with suspected or
confirmed influenza, regardless of
trimester of pregnancy
• Do not delay treatment because of
a negative rapid influenza
diagnostic test or inability to test
or while awaiting test results
Treatment
• Oseltamivir (Tamiflu®)
– 75 mg po bid for 5 days
– BEST if started within 48 hours of symptom
onset
• Oseltamivir (Tamiflu®) and zanamivir
(Relenza®) are FDA pregnancy category C
– Available data suggest not human teratogens
Tanaka et al. CMAJ 181:55-8, 2009
• Considering severity of disease, treatment
benefit outweighs potential risk
• Acetaminophen for fever
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
Post-exposure Chemoprophylaxis
• Consider if close contact with
suspected or confirmed case
• Zanamivir (Relenza®) Two 5mg
inhalations qd
• Oseltamivir (Tamiflu®) 75 mg qd
• 10 day duration
• Close monitoring and early treatment is
an alternative to chemoprophylaxis
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
– any other contact between persons likely to result in
exposure to respiratory droplets
ACIP Recommendations for
Seasonal Flu Vaccination
• Influenza vaccine is recommended
for people at increased risk of
severe infection, including women
who will be pregnant during
influenza season
• This includes all pregnant women
in any trimester
Need for Seasonal Flu
Vaccine
• Pregnant women who get influenza are
at higher risk for serious complications
• Influenza vaccine given during
pregnancy prevents febrile respiratory
illness in pregnant women and infants
and lab-proven influenza in infants up to
6 months of age
Zaman et al., NEJM 359:1555-64, 2008
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
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 374:451-8, 2009
Vaccine Types
• Live attenuated vaccine (not licensed for
use in pregnant women)
• Multidose inactivated vaccine
• Prefilled single dose inactivated vaccine
(preservative-free)
When to Administer
• Can be given at any time during
pregnancy
• Can also be given postpartum, providing
indirect protection for infants <6 months
• Recommended even for women who have
had influenza-like illness
How to Administer
• Inactivated vaccines against seasonal flu and
2009 H1N1 can be administered
simultaneously
– Use different anatomic sites
• 2009 H1N1 vaccine - ancillary supplies will
also be provided (needles, syringes, sharps
containers, alcohol swabs, vaccination
record card)
• 2009 H1N1 vaccine approved by FDA
– One dose for persons > 10 years of age
How to Obtain 2009 H1N1
Vaccine
• Vaccine expected to be available in October
• CDC will allocate vaccine to states based on
population
• States will determine where vaccine will be
shipped (mix of public and private settings)
• Contact state health department to express
interest in receiving vaccine (list of contacts
on CDC website)
2009 H1N1 Vaccine
Financing
• Vaccine available at no-cost for providers
• Providers CANNOT charge a fee for vaccine
since it is being provided free of charge by the
federal government
• Providers can bill insurance or charge the
patient a vaccine administration fee
– Patient cannot be charged more than regional
Medicare vaccine administration fee
2009 H1N1 Vaccine
Financing (continued)
• Providers are encouraged to vaccinate
under- or uninsured patients
• If unable, providers should refer these
patients to public health settings
2009 H1N1 Vaccine Safety
• Anticipated to be similar to seasonal
flu vaccine
• Clinical trials in pregnant women
began mid-September
CDC Interim Guidelines
• http://www.cdc.gov/h1n1flu
• http://www.cdc.gov/h1n1flu/pregnancy/
• http://www.cdc.gov/H1N1flu/clinician_preg
nant.htm
Conclusions
• During an influenza pandemic, pregnant
women are expected to be a high-risk
population, based on the experience with
previous pandemics and with seasonal
influenza
• Data available thus far suggest that
pregnant women are at increased risk for
complications and death from 2009 H1N1
influenza
Conclusions
• Pregnant women should be informed about
the signs and symptoms of 2009 H1N1
influenza
• Pregnant women who present with signs
and symptoms consistent with influenza
should be treated empirically with
oseltamivir
• Post-exposure prophylaxis with zanamivir
or oseltamivir can be considered for
pregnant women
Conclusions
• Both seasonal and 2009 H1N1 influenza
vaccines recommended for pregnant
women
• 2009 H1N1 vaccine safety expected to be
similar to seasonal influenza vaccine
• Providers should contact state health
department to express interest in obtaining
2009 H1N1 vaccine
Kevin A. Ault MD
Department of Gynecology and
Obstetrics
Emory University School of Medicine
Atlanta GA USA
“On the Ground” Planning
• GA State Meeting August 2009
• Most troublesome issues
– Isolation of mothers with illness
– Masks during labor
– Planning for new H1N1 vaccine
Influenza Vaccine During
Pregnancy
• Pregnancy Risk Assessment and
Monitoring System (PRAMS) from
Georgia and Rhode Island reported
in MMWR on Sept 11, 2009
• Questionnaire mailed to women 2-6
months postpartum
• GA and RI collected influenza
vaccine information starting in 2004
Influenza Vaccine During
Pregnancy
From MMWR Sept 11, 2009
Reasons given for not receiving influenza
vaccination --- Pregnancy Risk Assessment
Monitoring System, Georgia, 2006
Reason
Percentage
“I don’t usually get flu vaccine”
69.4 %
“My physician did not mention
anything about a flu vaccine
during my pregnancy”
44.5 %
“I was worried that the flu
vaccination might harm my baby”
28.1 %
“I was in my first trimester during
the flu season “
25.2 %
Potential interventions to improve influenza
vaccination rate in pregnant women
• Standing orders in office and hospital
settings
• Broadcast email to all employees
• Professional education at all levels
• “Best practices” review with department
head by individual provider ie quality
control
• Vaccine “champion”
Adopted from Mouzoon et al
Safety of influenza vaccination
during pregnancy
• 11 studies published between 1964
and 2008 about safety of influenza
vaccination during pregnancy
• None identified maternal or fetal
problems with influenza
vaccination
• One prospective randomized trial
showed significant benefits to
mothers and newborns
Data from Bhat et al ’05 – seasonal flu 2003-2004
Laboratory-Proven Influenza in Infants Whose
Mothers Received Influenza Vaccine vs Controls
Zaman et al., New Eng Journal of Medicine, 2008
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