COCA Conference Call – COCA Conference Call – National Obstetric Grand Rounds: National Obstetric Grand Rounds: Pandemic (H1N1) 2009 Influenza Pandemic (H1N1) 2009 Influenza

and Pregnancyand Pregnancy

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.

Denise J. Jamieson, MD MPHDivision of Reproductive Health

Centers for Disease Control and Prevention

Sonja A. Rasmussen, MD, MSNational Center on Birth Defects and Developmental Disabilities

Centers for Disease Control and Prevention

Kevin Ault, MDDepartment of Gynecology & Obstetrics

Emory University School of Medicine

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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)

• No evidence that they are more susceptible

• Increased mortality from influenza during previous pandemics (1918 & 1957)

• Increased risk of complications related to seasonal influenza

Pregnant women at increased risk for Pregnant women at increased risk for severe influenza illnesssevere influenza illness

1.72.1

5.1

0

2

4

6

8

1st trimester 2nd trimester 3rd trimester

Rat

e R

atio

sRisk of Hospital Admission for Respiratory Illness

during Influenza Season by Pregnancy Status* among Women with No Comorbidity,

Nova Scotia, 1990-2002

Dodds et al., CMAJ 176:463-8, 2007

*Compared to year before pregnancy

• 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 cell-mediated immunity

• These changes render pregnant women more susceptible and more severely affected by certain viral pathogens

Why are pregnant women at increased Why are pregnant women at increased risk for severe influenza illness?risk for severe influenza illness?

• 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

Fetal concerns regarding influenza during pregnancy

• 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

Special Health Care Delivery Challenges for Pregnant Women

Lu et al., Vaccine 26:1786-93, 2008

Data from National Health Interview Survey

Influenza Vaccination Coverage among Influenza Vaccination Coverage among Recommended Adult Populations, National Recommended Adult Populations, National

Health Interview Survey, 1989-2005Health Interview Survey, 1989-2005

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, 2009CDC, 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 4/15-5/5/2009)

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

Jamieson DJ et al., Lancet 374:451-8, 2009

• 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 15-June 16, 2009) (6/45 or 13% of total)

Presenting manifestations N (%)

Fever 33 (97%)

Cough 32 (94%)

Rhinorrhea 20 (59%)

Sore throat 17 (50%)

Headache 16 (47%)

Shortness of breath 14 (41%)

Vomiting 6 (18%)

Diarrhea 4 (12%)

Presenting Manifestations in Pregnant Women with Pandemic (H1N1) 2009

Influenza United States, April 15 to May 18, 2009United States, April 15 to May 18, 2009

Jamieson DJ et al., Lancet 374:451-8, 2009

Pregnancy Trimester at Time of Pandemic (H1N1) 2009

Influenza InfectionUnited States, April 15-May 18, 2009

9

56

26

9

0

10

20

30

40

50

60

1sttrimester

2ndtrimester

3rdtrimester

Unknown

Trimester of Pregnancy

Pe

rce

nt

Jamieson DJ et al., Lancet 374:451-8, 2009

PopulationAdmission Rate per

100,000 (95% CI)

Pregnant women 0.32 (0.13-0.52)

General Population 0.076 (0.07-0.09)

Admission Rates for Pregnant Women and General Population with

Pandemic (H1N1) 2009 Influenza United States, April 15 to May 18, 2009United States, April 15 to May 18, 2009

Jamieson DJ et al., Lancet 374:451-8, 2009

Risk Ratio 4.3, 95% CI 2.3-7.8

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

Deaths in Pregnant Women due to Pandemic (H1N1) 2009 Influenza

United States, April 15 to June 16, 2009United States, April 15 to June 16, 2009

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

Test MethodTime 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

http://www.cdc.gov/flu/professionals/diagnosis/0809testingguide.htm www.cdc.gov/h1n1flu/guidance/rapid_testing.htm

*rRT-PCR – real-time reverse transcriptase polymerase chain reaction

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_pregnant.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 WhoseMothers Received Influenza Vaccine vs Controls

Zaman et al., New Eng Journal of Medicine, 2008

Thank you!

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