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Pandemic swine-origin influenza A (H1N1) emerged as a
threatening pathogen in April 2009. Although this specific
strain of influenza is dangerous to many subsets of individ-
uals, including the very young or people with chronic med-
ical conditions (Table 1), it has targeted pregnant women at
an alarming rate and with potential serious sequelae. For
these reasons, it is imperative that providers of prenatal care
become familiar with the diagnosis and treatment of preg-
nant women with suspected H1N1 influenza. After reading
this review, clinicians should be able to recognize patients
with influenza-like illness and know how to treat such
patients during both pregnancy and the postpartum period.
In addition, providers should understand the importance of
vaccinating all pregnant patients against influenza.
Emerging Pathogen
The current H1N1 influenza pandemic arose rapidly. In
early April 2009, young, healthy people in several areas of
Mexico began to develop a severe pneumonia-like illness.
The first reported outbreak of an influenza-like illness was
in a small community in the state of Veracruz on April 12,
2009. On April 17, 2009, a case of atypical pneumonia in
Oaxaca State, a different region of Mexico, was reported.
Laboratory testing revealed that these cases, as well as oth-
ers reported on April 23, 2009, were confirmed as H1N1
virus. The Mexican Ministry of Health thereby issued an
alert ordering all suspected cases of influenza-like illness
be reported.
As cases of this novel influenza-like illness were being
reported in Mexico, others began to emerge in the United
States, with five confirmed cases in the United States as of
April 21, 2009. Sequence analysis revealed that patients in
Mexico were infected with the same influenza strain as
two children residing in California. Illness began to
spread; as ofApril 27, 2009, there were 26 confirmed cases
of novel H1N1 influenza in Mexico, and 1 day later, the
Centers for Disease Control and Prevention (CDC) report-
ed 64 confirmed cases in the United States.1
On April 27, 2009, the World Health Organization
(WHO) raised the worldwide alert to pandemic level 4,
indicating confirmed human-to-human transmission able
to cause community-level outbreaks. Just 2 days later,
WHO raised the alert to pandemic level 5, indicating that
H1N1 Influenza and Pregnancy
Barbra Fisher, MD, PhD, and Ronald S. Gibbs, MD
Learning Objectives: After participating in this activity, the obstetrician/gynecologist should be better able to:
1. Properly diagnose and treat H1N1 influenza in pregnant patients.
2. Implement influenza vaccination during pregnancy appropriately.
3. Provide recommendations regarding postpartum influenza management.
Lippincott Continuing Medical Education Institute, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical
education for physicians.
Lippincott Continuing Medical Education Institute, Inc., designates this educational activity for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians
should only claim credit commensurate with the extent of their participation in the activity.
To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed answer form, answering at least seven of the 10 quiz questions
correctly. This activity expires on May 14, 2011.
A BIWEEKLY PUBLICATION FOR CONTINUING MEDICAL
EDUCATION IN OBSTETRICS AND GYNECOLOGY
POSTGRADUATE
OBSTETRICS&GYNECOLOGY
POSTGRADUATE
OBSTETRICS&GYNECOLOGY
Dr. Fisher is Fellow/Instructor, and Dr. Gibbs is Professor and Associate Dean for
ContinuingMedicalEducation,DepartmentofObstetricsandGynecology,University
of Colorado Health Sciences Center, Mail Stop F763, Anschutz Inpatient Pavilion,
12605 E. 16thAvenue, Aurora, CO 60045; E-mail: barbra.fisher@ucdenver.edu.
All faculty and staff in a position to control the content of this CME activity
and their spouses/life partners (if any) have disclosed that they have no finan-
cial relationships with, or financial interests in, any commercial companies
pertaining to this educational activity.
VOLUME 30 • NUMBER 9
May 15, 2010
Table 1. Health Conditions That Increase Risk of Hospitalization
from 2009 H1N1 Influenza
Lung disease
Asthma
Chronic obstructive pulmonary disease
Diabetes
Heart conditions
Neurologic disease
Pregnancy
PGO09.qxd:Layout 1 3/31/10 2:20 PM Page 1
Postgraduate Obstetrics & Gynecology May 15, 2010
2
The continuing education activity in Postgraduate Obstetrics & Gynecology is intended for obstetricians, gynecologists, and
other health care professionals with an interest in the diagnosis and treatment of obstetric and gynecological conditions.
Postgraduate Obstetrics & Gynecology (ISSN 0194-3898) is published biweekly by Lippincott Williams & Wilkins, Inc., 16522 Hunters
Green Parkway, Hagerstown, MD 21740-2116.Customer Service Manager,Audrey Dyson:Phone (800) 787-8981 or (410) 528-8572,
24-Hour Fax (410) 528-4105,or E-mail audrey.dyson@wolterskluwer.com.Visit our website at LWW.com.Publisher, Matthew Jozwiak.
Copyright 2010 Lippincott Williams & Wilkins. Priority Postage paid at Hagerstown, MD,
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Opinions expressed do not necessarily reflect the views of the Publisher, Editor, or Editorial Board. A mention of products or services does
not constitute endorsement. All comments are for general guidance only; professional counsel should be sought for specific situations.
a worldwide pandemic was probably immi-
nent. A short time later, on June 11, 2009,
WHO declared a level 6 pandemic, the high-
est possible level, and the first such level in
more than 40 years. A level 6 pandemic indi-
cates that there are community-level out-
breaks in at least two different WHO regions.
When Margaret Chan, WHO Director-
General, made this declaration, she also noted
that “No previous pandemic has been detect-
ed so early or watched so closely, in real-
time, right at the very beginning.” The early
course of spread of H1N1 influenza was
rapid and widespread.2,3
Through July 23, 2009, a total of 43,677
laboratory-confirmed infections had been
reported in the United States by the 50 states
and the District of Columbia, including
5009 hospitalizations and 302 deaths.4
The
most recent CDC estimates5
reveal that from
April through December 12, 2009, between
39 and 80 million cases occurred in the
United States, with between 173,000 and
362,000 H1N1-related hospitalizations dur-
ing this period. These estimates are based on
mathematical models, as not all patients are
seen by health care providers, and not all
cases are confirmed with laboratory tests.
Susceptible Populations
Surveillance of H1N1 influenza illness has
revealed that patients affected most seriously
by this illness, similar to seasonal influenza
outbreaks, often have underlying chronic
medical conditions. Such conditions account
for more than 70% of cases. These underly-
ing medical conditions include asthma
(28%), chronic obstructive pulmonary dis-
ease (8%), diabetes (15%), immunosuppres-
sion (15%), and chronic cardiovascular dis-
ease (15%).6
In contrast to seasonal influenza, severe
illness has also been reported among
young, healthy persons without any under-
lying medical conditions. The age distribu-
tion of patients affected with novel H1N1
influenza is much younger than that typi-
cally seen in seasonal influenza outbreaks.
Almost half of the hospitalizations result-
ing from this illness have involved persons
under the age of 18 years, with more than
one-third of the patients being between the
ages of 18 and 49 years. Pregnancy has
also been identified as a condition portend-
ing a potential serious course of illness
after infection with H1N1 influenza virus.
H1N1 Influenza Virus and
Pregnancy
Pregnant women infected with H1N1
influenza virus have been more likely to suf-
fer severe complications than other popula-
tion groups infected with this virus. The
increased minute ventilation, reduced tidal
volumes, and decreased functional residual
capacity of normal pregnancy physiology
leave less reserve capacity for significant
stress on pulmonary function.7
Immune sys-
tem differences in pregnancy may account
for increased severity of disease.8
Finally,
there is also speculation that the higher mor-
bidity and mortality among pregnant patients
is related to the overall greater metabolic
demands of pregnancy.9
One of the first publications to address
2009 H1N1 influenza virus infection dur-
ing pregnancy in the United States sum-
marized cases identified during the first
month of this outbreak.10
In this report,
the estimated rate of hospital admission
for pandemic H1N1 influenza virus in
pregnant women was more than four-fold
EDITORS
William Schlaff, MD
Professor and Vice Chairman,
Chief of Reproductive
Endocrinology, Department
of Obstetrics and
Gynecology, University of
Colorado School of Medicine,
Aurora, Colorado
Lorraine Dugoff, MD
Associate Professor, Section of
Maternal Fetal Medicine,
Department of Obstetrics and
Gynecology, University of
Colorado School of Medicine,
Aurora, Colorado
FOUNDING EDITORS
Edward E. Wallach, MD
Roger D. Kempers, MD
ASSOCIATE EDITORS
J. Christopher Carey, MD
Denver Health Medical Center
Denver, Colorado
Susan A. Davidson, MD
University of Colorado
Aurora, Colorado
Marc A. Fritz, MD
University of North Carolina
Chapel Hill, North Carolina
Alice R. Goepfert, MD
University of Alabama,
Birmingham, Alabama
Veronica Gomez-Lobo, MD
Washington Hospital Center
Washington, District of Columbia
Hope K. Haefner, MD
University of Michigan
Ann Arbor, Michigan
Nancy Hueppchen, MD
Johns Hopkins University
Baltimore, Maryland
Bradley S. Hurst, MD
Carolinas Medical Center
Charlotte, North Carolina
Christine Isaacs, MD
VCU Medical Center
Richmond, VA
Julia V. Johnson, MD
University of Vermont
Burlington, Vermont
Peter G. McGovern, MD
University of Medicine and
Dentistry of New Jersey
Newark, New Jersey
William D. Petok, PhD
Clinical Psychologist
Baltimore, Maryland
Lynn L. Simpson, MD
Columbia University Medical
Center
New York, NY
Robert K. Zurawin, MD
Baylor College of Medicine
Houston, TX
PGO09.qxd:Layout 1 3/31/10 2:20 PM Page 2
higher than it was in the general population (0.32 per
100,000 pregnant women compared with 0.076 per 100,000
population at risk). In addition, a high proportion of the early
deaths attributed to H1N1 influenza virus was in pregnant
women; this special population accounted for more than
10% of deaths.
Early in the course of the 2009 H1N1 influenza out-
break, the California Department of Public Health initiat-
ed a statewide surveillance for patients hospitalized with
or who died from this virus. The California experience
was reported recently in a number of publications11,12
and
revealed findings for H1N1 influenza infection during
pregnancy that were similarly concerning to early reports
by the CDC. In 10% of patients with the most serious
complications of this virus, requiring hospitalization or
resulting in death, were pregnant. Of these severe cases,
95% of the pregnant patients were infected in the second
or third trimester, and almost one-fifth required intensive
care. The severity of illness seen in pregnancy has not
been limited to the United States experience. In Australia
and New Zealand, pregnant women represent 1% of the
population yet accounted for 9.1% of the total patients
admitted to the intensive care unit with H1N1 infection
from June 1 through August 31, 2009.13
The rapid clinical deterioration observed in some preg-
nant patients infected with H1N1 influenza virus appears
to be different than that associated with seasonal influen-
za.12
In the reported California series, one quarter of
women requiring mechanical ventilation were severely
ill at the time of presentation and required intubation on
the day of admission. There were six emergency deliver-
ies in the intensive care unit, implying that the condition
of these patients was too unstable to transfer to an appro-
priate labor and delivery unit or operating room.
In addition to death, serious complications of H1N1
influenza virus include viral pneumonitis, acute respirato-
ry distress syndrome, secondary bacterial pneumonia, and
exacerbation of airflow limitation. Complications specific
to pregnancy include adverse maternal and neonatal out-
comes such as preterm labor, preterm birth, and pregnancy
loss. Nonreassuring fetal status (tachycardia most com-
monly) and febrile morbidity have also been described.3,14
Diagnosis and Treatment
Symptoms
Patients with novel H1N1 influenza present with an
influenza-like illness, most commonly with fever of
37.8°C (100.0°F) and cough or sore throat. Other report-
ed symptoms include chills, body aches/muscle pain,
headache, fatigue, runny nose, and occasionally diarrhea
and vomiting. Some patients with this illness do not have
a fever, making it important that providers of prenatal
care have a low threshold for diagnosis and treatment
based on clinical suspicion of disease.
Diagnosis
Definitive diagnosis of H1N1 influenza virus relies on
a nasopharyngeal or oropharyngeal swab, nasal aspirate,
or combined nasopharyngeal and oropharyngeal swab for
sampling. A rapid influenza antigen test has been used
commonly for patients suspected of having H1N1
influenza. The rapid test evaluates for influenza A, for
which H1N1 influenza virus is a subtype, and positive
tests are helpful so long as seasonal influenza A is not yet
circulating in the community. An advantage of the rapid
test is that results are available in 30 minutes. However,
these rapid tests have the ability to detect only 10% to
70% of H1N1 influenza; a negative rapid test is unreli-
able due to this high false-negative rate. Real-time reverse
transcriptase polymerase chain reaction (RT-PCR) or cul-
ture is recommended for confirmation of H1N1 influenza.
For tracking purposes, the CDC defines a confirmed case
of novel H1N1 influenza as an influenza-like illness and
laboratory-confirmed H1N1 influenza A either by RT-
PCR or culture. A probable case is defined as influenza-
like illness in a person who has tested positive for influen-
za A by RT-PCR, but in whom a strain has not yet been
determined.15
Several days may be required to obtain definitive diag-
nosis of H1N1 influenza with RT-PCR assay or culture:
48 to 96 hours with nucleic acid amplification testing
such as RT-PCR, and 2 to 10 days for viral isolation in
tissue cell culture.
Although assays to diagnose H1N1 influenza infection
definitively are available, with rapidly rising numbers of
cases and because providers should not wait for the
results of testing to initiate therapy, some authorities rec-
ommend that providers treat patients without comorbidi-
ty or severe symptoms presumptively and without collec-
tion of specimens for laboratory testing. The American
College of Obstetricians and Gynecologists (ACOG) has
provided a triage algorithm with recommendations for
over-the-phone antiviral therapy in appropriate candi-
dates.16
At some institutions such as the University of
Colorado Denver, however, face-to-face patient evalua-
tion with H1N1 influenza testing is recommended prior
to use of antiviral medication.
Treatment
Because rapid clinical deterioration has been observed
among pregnant patients, the CDC has recommended
that a high priority is to “treat pregnant women with
influenza-like illness as soon as possible; treatment
should not be withheld pending results of testing for
influenza, if testing is done.” On October 15, 2009,
ACOG revealed a recommended triage algorithm for
managing pregnant patients with suspected illness.15
This
algorithm helps providers determine which patients need
to be evaluated immediately based on signs, symptoms,
and other medical history, and it recommends initiation
of antiviral medications for all such patients. The rapid
test has a high false-negative rate and definitive testing is
time-prohibitive when making clinical decisions.
The treatment of choice for H1N1 influenza virus16
is
oseltamivir (75 mg orally twice daily for 5 days) or
zanamivir (two 5-mg inhalations twice daily for 5 days)
May 15, 2010 Postgraduate Obstetrics & Gynecology
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Postgraduate Obstetrics & Gynecology May 15, 2010
4
(Table 2).17
Both of these medications are pregnancy cate-
gory C, and no adverse outcomes related to these medica-
tions have yet to be reported in humans. In vitro studies using
human placentas reveal incomplete transfer of oseltamivir
carboxylate, the active metabolite of oseltamivir, resulting in
minimal accumulation in the fetus. Both oseltamivir and
zanamivir are FDA-approved for use in pregnancy, and both
are safe to take in all three trimesters of pregnancy.18
Zanamivir, because it is an inhalational medication, should
be avoided in women with underlying respiratory conditions
such as asthma. In addition to antiviral medications, support-
ive care is also recommended. Acetaminophen is the recom-
mended antipyretic for use in pregnancy.
For pregnant women with close contact to someone
with H1N1 influenza—defined by the CDC as having
cared for or lived with a person who has confirmed, prob-
able, or suspected influenza, or having been in a setting
where there was a high likelihood of contact with respi-
ratory droplets and/or body fluids of such a person—
postexposure antiviral chemoprophylaxis is recommend-
ed. Medications prescribed for prophylaxis are the same
as treatment medications, but the recommended dosages
differ. Oseltamivir is prescribed as 75-mg capsules once
daily for 10 days, and zanamivir is prescribed as two 5-
mg inhalations once daily for 10 days. It is recommend-
ed that the duration of postexposure chemoprophylaxis is
10 days after the last known exposure.
Postpartum Management
Studies have revealed that postpartum patients appear to
have a response to the H1N1 influenza virus similar to that of
pregnant women.12
The CDC includes women up to 2 weeks
postpartum, including following pregnancy loss, as a high-
risk group for H1N1 influenza-associated complications. In
the immediate postpartum period, patients are in transition to
normal immune, cardiac, and respiratory function and hence
are at increased risk of influenza-related complications. In the
series of patients reported to be most ill in California, there
were several hospitalized patients that had an onset of symp-
toms within 2 weeks after delivery. Of eight reported cases,
half required intensive care, and two patients died.
Treatment and chemoprophylaxis of postpartum patients
are similar to those for the pregnant population. The CDC
recommends the use of either oseltamivir or zanamivir in
postpartum patients, at dosing suggested above.
Interestingly, the manufacturer of oseltamivir does not rec-
ommend its use during lactation.18
Risks and benefits need
to be considered on an individual basis, with an under-
standing that the immediate postpartum period is a high-
risk time for H1N1 influenza-related complications.
For patients with active infection during recovery and
the immediate postpartum period, it is recommended that
the infant be separated from the mother until she has
received antiviral medications for at least 48 hours, is
without fever for 24 hours without antipyretics, and can
control cough and respiratory secretions. It is recommend-
ed that lactation be initiated with the use of a breast pump;
the infant should be fed with the mother’s milk by a
healthy caregiver. Antiviral medication is not a contraindi-
cation to breastfeeding. Once the above criteria are met
and the mother and infant are able to initiate direct contact,
it is recommended that the mother protect the newborn
from droplet exposure by washing her hands with soap and
water, wearing a face mask, and observing all respiratory
hygiene and cough etiquette guidelines. These precautions
should be observed for 7 days after symptom onset or 24
hours after resolution of symptoms, whichever is longer.
The infant should be monitored closely for symptoms of
influenza illness, and if such symptoms develop, notify the
pediatric team immediately. Although antiviral medica-
tions are not recommended for infants under the age of 1
year, the FDA has issued an Emergency Use Authorization
for infants less than 1 year old.19
Transmission
2009 H1N1 influenza virus appears to be transmitted
from person to person through close contact in ways sim-
ilar to seasonal influenza viruses. The primary mode of
spread is thought to be large droplet transmission and
transmission by direct contact with mucous membranes
or small-particle droplet nuclei.20
Prevention
It is recommended that healthcare workers use respirato-
ry protection, such as an N95 filtering face-piece respira-
tor, when entering the rooms of patients with suspected or
confirmed H1N1 influenza. Persons with suspected or
confirmed illness should be reminded to use appropriate
respiratory and hand hygiene precautions, such as frequent
hand-washing with soap and water; not touching eyes,
nose, or mouth; avoiding close contact with others; and
staying at home during the most infectious period. The
CDC recommends that infected persons stay home for at
least 24 hours after fever is gone without the use of
antipyretic medications. Interestingly, these guidelines do
not apply to health care settings, in which the exclusion
period should be continued for 7 days from symptom onset
or until the resolution of symptoms, whichever is longer.20
Vaccination
ACOG is committed to the concept of immunizing preg-
nant women against influenza. Even prior to the current
H1N1 influenza pandemic,ACOG’s Committee on Obstetric
Practice supported the CDC’s expanded recommendation
that women who will be pregnant during the influenza sea-
son (October through May) should be vaccinated.According
Table 2. Antiviral Therapy and Chemoprophylaxis for H1N1
Influenza Virus
Agent Treatment Chemoprophylaxis
Oseltamivir 75-mg capsule twice 75-mg capsule once daily
(Tamiflu) daily for 5 days for 10 days
Zanamivir Two 5-mg inhalations Two 5-mg inhalations
(Relenza) (10 mg total) twice (10 mg total) once
daily for 5 days daily for 10 days
PGO09.qxd:Layout 1 3/31/10 2:20 PM Page 4
to the November 2004 ACOG Committee Opinion entitled
“Influenza Vaccination and Treatment During Pregnancy,”
reaffirmed in 2006, “Influenza vaccination is an essential ele-
ment of prenatal care.”21
Vaccination is important due to con-
cerns regarding influenza illness in pregnancy, as well as
benefits to the neonate. Because infants age 6 months or
younger do not respond to the influenza vaccine, immuniz-
ing pregnant women confers protection to their fetuses.
The timing of the novel 2009 H1N1 strain of influenza
was such that the seasonal influenza vaccination devel-
oped for distribution in fall 2009 did not confer protection
against this strain. Development of an H1N1 influenza
vaccine began in May 2009, soon after emergence of the
pathogen, and it was first available several months later. In
many areas, distribution began in October 2009. Initially,
there were concerns regarding a shortage of vaccine.
Pregnant women were among the high-risk groups target-
ed to receive the vaccination when first available.
Concerns regarding potential shortages have been largely
unfounded. In the 2010 influenza season, it has been rec-
ommended that pregnant women receive vaccinations for
both seasonal influenza and the H1N1 strain. These injec-
tions may be administered on the same day; however, it is
recommended that they be administered at different sites
on the body, such as one upper extremity followed by the
contralateral extremity for the second injection.
Both seasonal and H1N1 influenza vaccines are avail-
able in either inactivated form, for intramuscular injec-
tion, or live form administered via nasal spray. Only the
inactivated, intramuscular form is considered safe for use
during pregnancy. It can be administered safely and
effectively in all three trimesters.
Many studies have demonstrated the safety of influenza
vaccination during pregnancy. A recent review highlights
these data.22
In addition to published studies, which include
prospective and retrospective cohorts, the Vaccine Adverse
Event Reporting System (VAERS), cosponsored by the CDC
and the FDA, contains a database of reports regarding
influenza vaccination during pregnancy.23
This postmarket-
ing surveillance system entails voluntary reporting of
adverse events by patients, family members, and health care
providers. Some adverse events are considered nonserious,
such as discomfort at the injection site, whereas others are
considered serious, such as death thought to be related to vac-
cine administration.
As of December 31, 2009, 99.3 million H1N1 vaccines
had been shipped to vaccination providers in the United
States, although the precise number of vaccines administered
is unknown. After H1N1 vaccination (to both pregnant and
nonpregnant populations), VAERS had received 7326
adverse event reports (approximately 70 events per 1 million
vaccinations administered), with the vast majority (94%) of
reported adverse events classified as nonserious. Only 6% of
reports (440) were classified as serious. The proportion of
serious events reported for the H1N1 vaccination was not
different than that calculated for the 2009 seasonal influenza
vaccine. In addition, no new or unusual events or patterns of
adverse events have emerged since administration of this
new vaccine began.
Summary
Since the first case of H1N1 influenza illness was diag-
nosed in early April 2009, its rapid spread led to a world-
wide pandemic. Pregnant women infected with H1N1
virus have been more likely to suffer severe complica-
tions compared with other population groups. In addition
to increased mortality, other serious complications of
H1N1 virus include viral pneumonitis, ARDS, secondary
bacterial pneumonia, and exacerbation of airflow limita-
tion. Complications specific to pregnancy include
adverse maternal and neonatal outcomes such as preterm
labor, preterm birth, and pregnancy loss. For these rea-
sons, recognition of symptoms and prompt treatment,
without awaiting the results of diagnostic testing, is
essential. The most recent query of the CDC reveals that
cases are now declining.
After reading this continuing medical education review
about H1N1 influenza in pregnancy, readers should be
better able to diagnose and treat such infections properly
during both pregnancy and the postpartum period. In
addition, such cases should continue to decline as more
and more patients are properly vaccinated, with recom-
mendations for implementing an immunization program
as outlined in this review.
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2. World Health Organization. Influenza A (H1N1): Pandemic alert phase 6
declared, of moderate severity. Available at: www.euro.who.int/influenza/
AH1N1/20090611_11.
3. Carlson A, Thung SF, Norwitz ER. H1N1 influenza in pregnancy: what all
obstetric care providers ought to know. Rev Obstet Gynecol 2009;2:139-145.
4. Reed C, Angula FJ, Swerdlow DL, et al. Estimates of the prevalence of
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tions regarding 2009 H1N1 influenza in intrapartum and postpartum hospi-
tal settings. Available at: www.cdc/gov/h1n1flu/guidance/obstetric.htm.
15. Centers for Disease Control and Prevention. H1N1 flu: diagnosis and lab
testing. Available at: www.cdc.gov/h1n1flu/diagnosis.
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(‘Swine flu’) updates. Available at: www.acog.org/departments/dept_
notice.cfm?recno=20&bulletin=4973.
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influenza-like illness. Available at: www.acog.org/departments/resource
Center/2009H1N1TriageTreatment.pdf.
18. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation,
7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005.
19. Centers for Disease Control and Prevention. 2009 H1N1 flu (swine flu)
and feeding your baby: what parents should know. Available at:
www.cdc/gov/h1n1flu/infantfeeding.htm.
20. Centers for Disease Control and Prevention. H1N1 flu: infection control.
Available at: www.cdc/gov/h1n1flu/infectioncontrol/.
21. ACOG Committee on Obstetric Practice. ACOG committee opinion num-
ber 305, November 2004. Influenza vaccination and treatment during
pregnancy. Obstet Gynecol 2004;104:1125-1126.
22. Tamma PD, Ault KA, del Rio C, et al. Safety of influenza vaccination dur-
ing pregnancy. Am J Obstet Gynecol 2009;201:547-552.
23. Centers for Disease Control and Prevention. Summary of 2009 monova-
lent H1N1 influenza vaccine data: vaccine adverse event reporting sys-
tem. Data through January 15, 2010. Available at: http://vaers.hhs.gov/
resources/2010H1N1Summary_Jan08.pdf.
Postgraduate Obstetrics & Gynecology May 15, 2010
6
1. Influenza vaccination is safe for use in pregnancy during
A. the first trimester
B. the second trimester
C. the third trimester
D. all trimesters
2. A pregnant patient calls the office at 4 p.m. on Friday after-
noon reporting a sore throat and temperature of 100.5°F.
You should
A. ask her to take acetaminophen and call back if symp-
toms worsen
B. call in an antiviral medication prescription to the local
pharmacy and ask her to call your office if she feels worse
C. advise her to go to the nearest emergency department
immediately
3. A patient with active H1N1 influenza infection should be
advised to discard breast milk while taking oseltamivir.
A. True
B. False
4. Which of the following medications should be prescribed for
H1N1 influenza infection in a patient who is 23 weeks preg-
nant and manages asthma with chronic corticosteroids?
A. Oseltamivir
B. Zanamivir
C. Both of the above
D. Neither of the above
5. A pregnant health care worker on day 3 of oseltamivir use
has been afebrile for 48 hours. She may return to work
A. at this time
B. after completion of the 5-day course of antiviral medication
C. 72 hours after being afebrile and without symptoms
D. 7 days after resolution of symptoms
6. At the first prenatal visit, a patient reports that she has not
yet received either an H1N1 influenza vaccine or the sea-
sonal influenza vaccine. You should
A. administer the H1N1 vaccine and have her return in 1
week for her seasonal influenza vaccine
B. administer the seasonal influenza vaccine and have
her return in 1 week for her H1N1 vaccine
C. administer both vaccinations at this visit but on con-
tralateral extremities
D. explain that as it is February and past the peak time for
influenza infection this year, she does not need either
vaccination
7. You are seeing an otherwise healthy pregnant patient in the
clinic who you suspect has H1N1 influenza. Which one of
the following regimens should you prescribe?
A. Oseltamivir 75 mg twice daily for 5 days
B. Oseltamivir 75 mg once daily for 10 days
C. Tylenol 650 mg PO every 6 hours as needed for fever
D. A and C
8. A patient calls the office 1 week postpartum to report fever
and cough. You tell her
A. she needs to be treated for H1N1 influenza, as the
immediate postpartum period is associated with high
risk of complications
B. she is no longer pregnant and thus no longer needs
antiviral medication, but she should call the office if her
symptoms worsen
C. she should see her internist or family physician, as you
only evaluate pregnant patients
9. Fever is invariably present at some point in the course of
disease in a patient with H1N1 influenza illness.
A. True
B. False
10. A pregnant hospital employee escorts a patient infected
with H1N1 from the emergency department to an inpatient
unit. She then reads in the newspaper of the potential dan-
gers of H1N1 influenza during pregnancy and calls you to
advise her. You tell her
A. she needs to initiate antiviral therapy immediately
B. the CDC has defined close contact with an infected patient,
and this encounter does not constitute such an encounter
C. she should stay home from work tomorrow to see
whether symptoms of influenza arise, and if they do, to
call your office
To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed answer form, answering at least
seven of the 10 quiz questions correctly.Select the best answer and use a blue or black pen to completely fill in the corresponding box
on the enclosed answer form. Please indicate any name and address changes directly on the answer form.If your name and address do not
appear on the answer form, please print that information in the blank space at the top left of the page. Make a photocopy of the completed
answer form for your own files and mail the original answer form in the enclosed postage-paid business reply envelope.Your answer form must
be received by Lippincott CME Institute by May 14, 2011. Only two entries will be considered for credit. At the end of each quarter, all CME
participants will receive individual issue certificates for their CME participation in that quarter.Participants will receive CME certificates quarterly
in April, July, October, and the fourth quarter in January of the following year. For more information, call (800) 787-8981.
Online quiz instructions: To take the quiz online, go to http://cme.LWWnewsletters.com, and enter your username and password.
Your username will be the letters LWW (case sensitive) followed by the 12-digit account number on your mailing label.You may also
find your account number on the paper answer form mailed with your issue.Your password will be 1234; this password may not be
changed. Follow the instructions on the site.You may print your official certificate immediately. Please note: Lippincott CME Institute
will not mail certificates to online participants. Online quizzes expire at 11:59 pm Pacific Standard Time on the due date.
CME QUIZ: Volume 30, Number 9
PGO09.qxd:Layout 1 3/31/10 2:20 PM Page 6

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H1N1 Flu and Pregnancy

  • 1. 1 Pandemic swine-origin influenza A (H1N1) emerged as a threatening pathogen in April 2009. Although this specific strain of influenza is dangerous to many subsets of individ- uals, including the very young or people with chronic med- ical conditions (Table 1), it has targeted pregnant women at an alarming rate and with potential serious sequelae. For these reasons, it is imperative that providers of prenatal care become familiar with the diagnosis and treatment of preg- nant women with suspected H1N1 influenza. After reading this review, clinicians should be able to recognize patients with influenza-like illness and know how to treat such patients during both pregnancy and the postpartum period. In addition, providers should understand the importance of vaccinating all pregnant patients against influenza. Emerging Pathogen The current H1N1 influenza pandemic arose rapidly. In early April 2009, young, healthy people in several areas of Mexico began to develop a severe pneumonia-like illness. The first reported outbreak of an influenza-like illness was in a small community in the state of Veracruz on April 12, 2009. On April 17, 2009, a case of atypical pneumonia in Oaxaca State, a different region of Mexico, was reported. Laboratory testing revealed that these cases, as well as oth- ers reported on April 23, 2009, were confirmed as H1N1 virus. The Mexican Ministry of Health thereby issued an alert ordering all suspected cases of influenza-like illness be reported. As cases of this novel influenza-like illness were being reported in Mexico, others began to emerge in the United States, with five confirmed cases in the United States as of April 21, 2009. Sequence analysis revealed that patients in Mexico were infected with the same influenza strain as two children residing in California. Illness began to spread; as ofApril 27, 2009, there were 26 confirmed cases of novel H1N1 influenza in Mexico, and 1 day later, the Centers for Disease Control and Prevention (CDC) report- ed 64 confirmed cases in the United States.1 On April 27, 2009, the World Health Organization (WHO) raised the worldwide alert to pandemic level 4, indicating confirmed human-to-human transmission able to cause community-level outbreaks. Just 2 days later, WHO raised the alert to pandemic level 5, indicating that H1N1 Influenza and Pregnancy Barbra Fisher, MD, PhD, and Ronald S. Gibbs, MD Learning Objectives: After participating in this activity, the obstetrician/gynecologist should be better able to: 1. Properly diagnose and treat H1N1 influenza in pregnant patients. 2. Implement influenza vaccination during pregnancy appropriately. 3. Provide recommendations regarding postpartum influenza management. Lippincott Continuing Medical Education Institute, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Lippincott Continuing Medical Education Institute, Inc., designates this educational activity for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed answer form, answering at least seven of the 10 quiz questions correctly. This activity expires on May 14, 2011. A BIWEEKLY PUBLICATION FOR CONTINUING MEDICAL EDUCATION IN OBSTETRICS AND GYNECOLOGY POSTGRADUATE OBSTETRICS&GYNECOLOGY POSTGRADUATE OBSTETRICS&GYNECOLOGY Dr. Fisher is Fellow/Instructor, and Dr. Gibbs is Professor and Associate Dean for ContinuingMedicalEducation,DepartmentofObstetricsandGynecology,University of Colorado Health Sciences Center, Mail Stop F763, Anschutz Inpatient Pavilion, 12605 E. 16thAvenue, Aurora, CO 60045; E-mail: barbra.fisher@ucdenver.edu. All faculty and staff in a position to control the content of this CME activity and their spouses/life partners (if any) have disclosed that they have no finan- cial relationships with, or financial interests in, any commercial companies pertaining to this educational activity. VOLUME 30 • NUMBER 9 May 15, 2010 Table 1. Health Conditions That Increase Risk of Hospitalization from 2009 H1N1 Influenza Lung disease Asthma Chronic obstructive pulmonary disease Diabetes Heart conditions Neurologic disease Pregnancy PGO09.qxd:Layout 1 3/31/10 2:20 PM Page 1
  • 2. Postgraduate Obstetrics & Gynecology May 15, 2010 2 The continuing education activity in Postgraduate Obstetrics & Gynecology is intended for obstetricians, gynecologists, and other health care professionals with an interest in the diagnosis and treatment of obstetric and gynecological conditions. Postgraduate Obstetrics & Gynecology (ISSN 0194-3898) is published biweekly by Lippincott Williams & Wilkins, Inc., 16522 Hunters Green Parkway, Hagerstown, MD 21740-2116.Customer Service Manager,Audrey Dyson:Phone (800) 787-8981 or (410) 528-8572, 24-Hour Fax (410) 528-4105,or E-mail audrey.dyson@wolterskluwer.com.Visit our website at LWW.com.Publisher, Matthew Jozwiak. Copyright 2010 Lippincott Williams & Wilkins. Priority Postage paid at Hagerstown, MD, and at additional mailing offices. POSTMASTER: Send address changes to Postgraduate Obstetrics & Gynecology, Subscription Dept., Lippincott Williams & Wilkins, P.O. Box 1600, 16522 Hunters Green Parkway, Hagerstown, MD 21740-2116. PAID SUBSCRIBERS: Current issue and archives from 2004 on are now available FREE online at www.lwwnewsletters.com. Subscription rates: Personal: $368.98 US, $523.98 Foreign.Institutional: $729.98 US, $871.98 Foreign.In-training: $113.98 resident non- scored US, $113.98 Foreign. GST Registration Number: 895524239.Send bulk pricing requests to Publisher. Single copies: $37. COPY- ING: Contents of Postgraduate Obstetrics & Gynecology are protected by copyright. Reproduction, photocopying, and storage or trans- mission by magnetic or electronic means are strictly prohibited.Violation of copyright will result in legal action, including civil and/or crim- inal penalties. Permission to reproduce in any way must be secured in writing; e-mail journalpermissions@lww.com. For reprints, e-mail matt.westcoat@wolterskluwer.com. Opinions expressed do not necessarily reflect the views of the Publisher, Editor, or Editorial Board. A mention of products or services does not constitute endorsement. All comments are for general guidance only; professional counsel should be sought for specific situations. a worldwide pandemic was probably immi- nent. A short time later, on June 11, 2009, WHO declared a level 6 pandemic, the high- est possible level, and the first such level in more than 40 years. A level 6 pandemic indi- cates that there are community-level out- breaks in at least two different WHO regions. When Margaret Chan, WHO Director- General, made this declaration, she also noted that “No previous pandemic has been detect- ed so early or watched so closely, in real- time, right at the very beginning.” The early course of spread of H1N1 influenza was rapid and widespread.2,3 Through July 23, 2009, a total of 43,677 laboratory-confirmed infections had been reported in the United States by the 50 states and the District of Columbia, including 5009 hospitalizations and 302 deaths.4 The most recent CDC estimates5 reveal that from April through December 12, 2009, between 39 and 80 million cases occurred in the United States, with between 173,000 and 362,000 H1N1-related hospitalizations dur- ing this period. These estimates are based on mathematical models, as not all patients are seen by health care providers, and not all cases are confirmed with laboratory tests. Susceptible Populations Surveillance of H1N1 influenza illness has revealed that patients affected most seriously by this illness, similar to seasonal influenza outbreaks, often have underlying chronic medical conditions. Such conditions account for more than 70% of cases. These underly- ing medical conditions include asthma (28%), chronic obstructive pulmonary dis- ease (8%), diabetes (15%), immunosuppres- sion (15%), and chronic cardiovascular dis- ease (15%).6 In contrast to seasonal influenza, severe illness has also been reported among young, healthy persons without any under- lying medical conditions. The age distribu- tion of patients affected with novel H1N1 influenza is much younger than that typi- cally seen in seasonal influenza outbreaks. Almost half of the hospitalizations result- ing from this illness have involved persons under the age of 18 years, with more than one-third of the patients being between the ages of 18 and 49 years. Pregnancy has also been identified as a condition portend- ing a potential serious course of illness after infection with H1N1 influenza virus. H1N1 Influenza Virus and Pregnancy Pregnant women infected with H1N1 influenza virus have been more likely to suf- fer severe complications than other popula- tion groups infected with this virus. The increased minute ventilation, reduced tidal volumes, and decreased functional residual capacity of normal pregnancy physiology leave less reserve capacity for significant stress on pulmonary function.7 Immune sys- tem differences in pregnancy may account for increased severity of disease.8 Finally, there is also speculation that the higher mor- bidity and mortality among pregnant patients is related to the overall greater metabolic demands of pregnancy.9 One of the first publications to address 2009 H1N1 influenza virus infection dur- ing pregnancy in the United States sum- marized cases identified during the first month of this outbreak.10 In this report, the estimated rate of hospital admission for pandemic H1N1 influenza virus in pregnant women was more than four-fold EDITORS William Schlaff, MD Professor and Vice Chairman, Chief of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, Colorado Lorraine Dugoff, MD Associate Professor, Section of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, Colorado FOUNDING EDITORS Edward E. Wallach, MD Roger D. Kempers, MD ASSOCIATE EDITORS J. Christopher Carey, MD Denver Health Medical Center Denver, Colorado Susan A. Davidson, MD University of Colorado Aurora, Colorado Marc A. Fritz, MD University of North Carolina Chapel Hill, North Carolina Alice R. Goepfert, MD University of Alabama, Birmingham, Alabama Veronica Gomez-Lobo, MD Washington Hospital Center Washington, District of Columbia Hope K. Haefner, MD University of Michigan Ann Arbor, Michigan Nancy Hueppchen, MD Johns Hopkins University Baltimore, Maryland Bradley S. Hurst, MD Carolinas Medical Center Charlotte, North Carolina Christine Isaacs, MD VCU Medical Center Richmond, VA Julia V. Johnson, MD University of Vermont Burlington, Vermont Peter G. McGovern, MD University of Medicine and Dentistry of New Jersey Newark, New Jersey William D. Petok, PhD Clinical Psychologist Baltimore, Maryland Lynn L. Simpson, MD Columbia University Medical Center New York, NY Robert K. Zurawin, MD Baylor College of Medicine Houston, TX PGO09.qxd:Layout 1 3/31/10 2:20 PM Page 2
  • 3. higher than it was in the general population (0.32 per 100,000 pregnant women compared with 0.076 per 100,000 population at risk). In addition, a high proportion of the early deaths attributed to H1N1 influenza virus was in pregnant women; this special population accounted for more than 10% of deaths. Early in the course of the 2009 H1N1 influenza out- break, the California Department of Public Health initiat- ed a statewide surveillance for patients hospitalized with or who died from this virus. The California experience was reported recently in a number of publications11,12 and revealed findings for H1N1 influenza infection during pregnancy that were similarly concerning to early reports by the CDC. In 10% of patients with the most serious complications of this virus, requiring hospitalization or resulting in death, were pregnant. Of these severe cases, 95% of the pregnant patients were infected in the second or third trimester, and almost one-fifth required intensive care. The severity of illness seen in pregnancy has not been limited to the United States experience. In Australia and New Zealand, pregnant women represent 1% of the population yet accounted for 9.1% of the total patients admitted to the intensive care unit with H1N1 infection from June 1 through August 31, 2009.13 The rapid clinical deterioration observed in some preg- nant patients infected with H1N1 influenza virus appears to be different than that associated with seasonal influen- za.12 In the reported California series, one quarter of women requiring mechanical ventilation were severely ill at the time of presentation and required intubation on the day of admission. There were six emergency deliver- ies in the intensive care unit, implying that the condition of these patients was too unstable to transfer to an appro- priate labor and delivery unit or operating room. In addition to death, serious complications of H1N1 influenza virus include viral pneumonitis, acute respirato- ry distress syndrome, secondary bacterial pneumonia, and exacerbation of airflow limitation. Complications specific to pregnancy include adverse maternal and neonatal out- comes such as preterm labor, preterm birth, and pregnancy loss. Nonreassuring fetal status (tachycardia most com- monly) and febrile morbidity have also been described.3,14 Diagnosis and Treatment Symptoms Patients with novel H1N1 influenza present with an influenza-like illness, most commonly with fever of 37.8°C (100.0°F) and cough or sore throat. Other report- ed symptoms include chills, body aches/muscle pain, headache, fatigue, runny nose, and occasionally diarrhea and vomiting. Some patients with this illness do not have a fever, making it important that providers of prenatal care have a low threshold for diagnosis and treatment based on clinical suspicion of disease. Diagnosis Definitive diagnosis of H1N1 influenza virus relies on a nasopharyngeal or oropharyngeal swab, nasal aspirate, or combined nasopharyngeal and oropharyngeal swab for sampling. A rapid influenza antigen test has been used commonly for patients suspected of having H1N1 influenza. The rapid test evaluates for influenza A, for which H1N1 influenza virus is a subtype, and positive tests are helpful so long as seasonal influenza A is not yet circulating in the community. An advantage of the rapid test is that results are available in 30 minutes. However, these rapid tests have the ability to detect only 10% to 70% of H1N1 influenza; a negative rapid test is unreli- able due to this high false-negative rate. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) or cul- ture is recommended for confirmation of H1N1 influenza. For tracking purposes, the CDC defines a confirmed case of novel H1N1 influenza as an influenza-like illness and laboratory-confirmed H1N1 influenza A either by RT- PCR or culture. A probable case is defined as influenza- like illness in a person who has tested positive for influen- za A by RT-PCR, but in whom a strain has not yet been determined.15 Several days may be required to obtain definitive diag- nosis of H1N1 influenza with RT-PCR assay or culture: 48 to 96 hours with nucleic acid amplification testing such as RT-PCR, and 2 to 10 days for viral isolation in tissue cell culture. Although assays to diagnose H1N1 influenza infection definitively are available, with rapidly rising numbers of cases and because providers should not wait for the results of testing to initiate therapy, some authorities rec- ommend that providers treat patients without comorbidi- ty or severe symptoms presumptively and without collec- tion of specimens for laboratory testing. The American College of Obstetricians and Gynecologists (ACOG) has provided a triage algorithm with recommendations for over-the-phone antiviral therapy in appropriate candi- dates.16 At some institutions such as the University of Colorado Denver, however, face-to-face patient evalua- tion with H1N1 influenza testing is recommended prior to use of antiviral medication. Treatment Because rapid clinical deterioration has been observed among pregnant patients, the CDC has recommended that a high priority is to “treat pregnant women with influenza-like illness as soon as possible; treatment should not be withheld pending results of testing for influenza, if testing is done.” On October 15, 2009, ACOG revealed a recommended triage algorithm for managing pregnant patients with suspected illness.15 This algorithm helps providers determine which patients need to be evaluated immediately based on signs, symptoms, and other medical history, and it recommends initiation of antiviral medications for all such patients. The rapid test has a high false-negative rate and definitive testing is time-prohibitive when making clinical decisions. The treatment of choice for H1N1 influenza virus16 is oseltamivir (75 mg orally twice daily for 5 days) or zanamivir (two 5-mg inhalations twice daily for 5 days) May 15, 2010 Postgraduate Obstetrics & Gynecology 3 PGO09.qxd:Layout 1 3/31/10 2:20 PM Page 3
  • 4. Postgraduate Obstetrics & Gynecology May 15, 2010 4 (Table 2).17 Both of these medications are pregnancy cate- gory C, and no adverse outcomes related to these medica- tions have yet to be reported in humans. In vitro studies using human placentas reveal incomplete transfer of oseltamivir carboxylate, the active metabolite of oseltamivir, resulting in minimal accumulation in the fetus. Both oseltamivir and zanamivir are FDA-approved for use in pregnancy, and both are safe to take in all three trimesters of pregnancy.18 Zanamivir, because it is an inhalational medication, should be avoided in women with underlying respiratory conditions such as asthma. In addition to antiviral medications, support- ive care is also recommended. Acetaminophen is the recom- mended antipyretic for use in pregnancy. For pregnant women with close contact to someone with H1N1 influenza—defined by the CDC as having cared for or lived with a person who has confirmed, prob- able, or suspected influenza, or having been in a setting where there was a high likelihood of contact with respi- ratory droplets and/or body fluids of such a person— postexposure antiviral chemoprophylaxis is recommend- ed. Medications prescribed for prophylaxis are the same as treatment medications, but the recommended dosages differ. Oseltamivir is prescribed as 75-mg capsules once daily for 10 days, and zanamivir is prescribed as two 5- mg inhalations once daily for 10 days. It is recommend- ed that the duration of postexposure chemoprophylaxis is 10 days after the last known exposure. Postpartum Management Studies have revealed that postpartum patients appear to have a response to the H1N1 influenza virus similar to that of pregnant women.12 The CDC includes women up to 2 weeks postpartum, including following pregnancy loss, as a high- risk group for H1N1 influenza-associated complications. In the immediate postpartum period, patients are in transition to normal immune, cardiac, and respiratory function and hence are at increased risk of influenza-related complications. In the series of patients reported to be most ill in California, there were several hospitalized patients that had an onset of symp- toms within 2 weeks after delivery. Of eight reported cases, half required intensive care, and two patients died. Treatment and chemoprophylaxis of postpartum patients are similar to those for the pregnant population. The CDC recommends the use of either oseltamivir or zanamivir in postpartum patients, at dosing suggested above. Interestingly, the manufacturer of oseltamivir does not rec- ommend its use during lactation.18 Risks and benefits need to be considered on an individual basis, with an under- standing that the immediate postpartum period is a high- risk time for H1N1 influenza-related complications. For patients with active infection during recovery and the immediate postpartum period, it is recommended that the infant be separated from the mother until she has received antiviral medications for at least 48 hours, is without fever for 24 hours without antipyretics, and can control cough and respiratory secretions. It is recommend- ed that lactation be initiated with the use of a breast pump; the infant should be fed with the mother’s milk by a healthy caregiver. Antiviral medication is not a contraindi- cation to breastfeeding. Once the above criteria are met and the mother and infant are able to initiate direct contact, it is recommended that the mother protect the newborn from droplet exposure by washing her hands with soap and water, wearing a face mask, and observing all respiratory hygiene and cough etiquette guidelines. These precautions should be observed for 7 days after symptom onset or 24 hours after resolution of symptoms, whichever is longer. The infant should be monitored closely for symptoms of influenza illness, and if such symptoms develop, notify the pediatric team immediately. Although antiviral medica- tions are not recommended for infants under the age of 1 year, the FDA has issued an Emergency Use Authorization for infants less than 1 year old.19 Transmission 2009 H1N1 influenza virus appears to be transmitted from person to person through close contact in ways sim- ilar to seasonal influenza viruses. The primary mode of spread is thought to be large droplet transmission and transmission by direct contact with mucous membranes or small-particle droplet nuclei.20 Prevention It is recommended that healthcare workers use respirato- ry protection, such as an N95 filtering face-piece respira- tor, when entering the rooms of patients with suspected or confirmed H1N1 influenza. Persons with suspected or confirmed illness should be reminded to use appropriate respiratory and hand hygiene precautions, such as frequent hand-washing with soap and water; not touching eyes, nose, or mouth; avoiding close contact with others; and staying at home during the most infectious period. The CDC recommends that infected persons stay home for at least 24 hours after fever is gone without the use of antipyretic medications. Interestingly, these guidelines do not apply to health care settings, in which the exclusion period should be continued for 7 days from symptom onset or until the resolution of symptoms, whichever is longer.20 Vaccination ACOG is committed to the concept of immunizing preg- nant women against influenza. Even prior to the current H1N1 influenza pandemic,ACOG’s Committee on Obstetric Practice supported the CDC’s expanded recommendation that women who will be pregnant during the influenza sea- son (October through May) should be vaccinated.According Table 2. Antiviral Therapy and Chemoprophylaxis for H1N1 Influenza Virus Agent Treatment Chemoprophylaxis Oseltamivir 75-mg capsule twice 75-mg capsule once daily (Tamiflu) daily for 5 days for 10 days Zanamivir Two 5-mg inhalations Two 5-mg inhalations (Relenza) (10 mg total) twice (10 mg total) once daily for 5 days daily for 10 days PGO09.qxd:Layout 1 3/31/10 2:20 PM Page 4
  • 5. to the November 2004 ACOG Committee Opinion entitled “Influenza Vaccination and Treatment During Pregnancy,” reaffirmed in 2006, “Influenza vaccination is an essential ele- ment of prenatal care.”21 Vaccination is important due to con- cerns regarding influenza illness in pregnancy, as well as benefits to the neonate. Because infants age 6 months or younger do not respond to the influenza vaccine, immuniz- ing pregnant women confers protection to their fetuses. The timing of the novel 2009 H1N1 strain of influenza was such that the seasonal influenza vaccination devel- oped for distribution in fall 2009 did not confer protection against this strain. Development of an H1N1 influenza vaccine began in May 2009, soon after emergence of the pathogen, and it was first available several months later. In many areas, distribution began in October 2009. Initially, there were concerns regarding a shortage of vaccine. Pregnant women were among the high-risk groups target- ed to receive the vaccination when first available. Concerns regarding potential shortages have been largely unfounded. In the 2010 influenza season, it has been rec- ommended that pregnant women receive vaccinations for both seasonal influenza and the H1N1 strain. These injec- tions may be administered on the same day; however, it is recommended that they be administered at different sites on the body, such as one upper extremity followed by the contralateral extremity for the second injection. Both seasonal and H1N1 influenza vaccines are avail- able in either inactivated form, for intramuscular injec- tion, or live form administered via nasal spray. Only the inactivated, intramuscular form is considered safe for use during pregnancy. It can be administered safely and effectively in all three trimesters. Many studies have demonstrated the safety of influenza vaccination during pregnancy. A recent review highlights these data.22 In addition to published studies, which include prospective and retrospective cohorts, the Vaccine Adverse Event Reporting System (VAERS), cosponsored by the CDC and the FDA, contains a database of reports regarding influenza vaccination during pregnancy.23 This postmarket- ing surveillance system entails voluntary reporting of adverse events by patients, family members, and health care providers. Some adverse events are considered nonserious, such as discomfort at the injection site, whereas others are considered serious, such as death thought to be related to vac- cine administration. As of December 31, 2009, 99.3 million H1N1 vaccines had been shipped to vaccination providers in the United States, although the precise number of vaccines administered is unknown. After H1N1 vaccination (to both pregnant and nonpregnant populations), VAERS had received 7326 adverse event reports (approximately 70 events per 1 million vaccinations administered), with the vast majority (94%) of reported adverse events classified as nonserious. Only 6% of reports (440) were classified as serious. The proportion of serious events reported for the H1N1 vaccination was not different than that calculated for the 2009 seasonal influenza vaccine. In addition, no new or unusual events or patterns of adverse events have emerged since administration of this new vaccine began. Summary Since the first case of H1N1 influenza illness was diag- nosed in early April 2009, its rapid spread led to a world- wide pandemic. Pregnant women infected with H1N1 virus have been more likely to suffer severe complica- tions compared with other population groups. In addition to increased mortality, other serious complications of H1N1 virus include viral pneumonitis, ARDS, secondary bacterial pneumonia, and exacerbation of airflow limita- tion. Complications specific to pregnancy include adverse maternal and neonatal outcomes such as preterm labor, preterm birth, and pregnancy loss. For these rea- sons, recognition of symptoms and prompt treatment, without awaiting the results of diagnostic testing, is essential. The most recent query of the CDC reveals that cases are now declining. After reading this continuing medical education review about H1N1 influenza in pregnancy, readers should be better able to diagnose and treat such infections properly during both pregnancy and the postpartum period. In addition, such cases should continue to decline as more and more patients are properly vaccinated, with recom- mendations for implementing an immunization program as outlined in this review. REFERENCES 1. Update: Novel influenza A (H1N1) virus infections: worldwide, May 6, 2009. MMWR 2009;58:453-458. 2. World Health Organization. Influenza A (H1N1): Pandemic alert phase 6 declared, of moderate severity. Available at: www.euro.who.int/influenza/ AH1N1/20090611_11. 3. Carlson A, Thung SF, Norwitz ER. H1N1 influenza in pregnancy: what all obstetric care providers ought to know. Rev Obstet Gynecol 2009;2:139-145. 4. Reed C, Angula FJ, Swerdlow DL, et al. Estimates of the prevalence of pandemic (H1N1) 2009, United States, April-July 2009. Emerg Infect Dis [serial on the Internet]. 2009 Dec [Epub ahead of print]. 5. Centers for Disease Control and Prevention. CDC estimates of 2009 H1N1 influenza cases, hospitalizations and deaths in the united states, April–December 12, 2009. Available at: www.cdc.gov/h1n1flu/estimates/ April_December_12.htm 6. Jain S, Kamimoto L, Bramley AM, et al. Hospitalized patients with 2009 H1N1 influenza in the united states. N Engl J Med 2009;361:1935-1944. 7. Saleeby E, Chapman J, Morse J et al. H1N1 influenza in pregnancy: cause for concern. Obstet Gynecol 2009;114:885-891. 8. Gonzalez JM, Ofori E, Burd I, et al. Maternal mortality from systemic ill- ness: unraveling the contribution of the immune system. Am J Obstet Gynecol 2009;200:430.e1-8. 9. Phillippe M. Ob gyns on the front line in the H1N1 flu pandemic. Ob Gyn News 2009;Oct:24-25. 10. Jamieson DJ, Honein MA, Rasmussen SA, et al. Lancet 2009;374:451-458. 11. Louie JK, Acosta M, Winter K. et al. Factors associated with death or hos- pitalization due to pandemic 2009 influenza A (H1N1) infection in California. JAMA 2009;302:1896-1902. 12. Louie JK,Acosta M, Jamieson DJ, et al. Severe 2009 H1N1 influenza in preg- nant and postpartum women in California. N Engl J Med 2010;362:27-35. 13. ANZIC Influenza Investigators. Critical care services and 2009 H1N1 influen- za in Australia and New Zealand. N Engl J Med 2009;361(20):1925-1952. 14. Centers for Disease Control and Prevention. Interim guidance: considera- tions regarding 2009 H1N1 influenza in intrapartum and postpartum hospi- tal settings. Available at: www.cdc/gov/h1n1flu/guidance/obstetric.htm. 15. Centers for Disease Control and Prevention. H1N1 flu: diagnosis and lab testing. Available at: www.cdc.gov/h1n1flu/diagnosis. 16. American College of Obstetricians and Gynecologists. 2009 H1N1 (‘Swine flu’) updates. Available at: www.acog.org/departments/dept_ notice.cfm?recno=20&bulletin=4973. 17. American College of Obstetricians and Gynecologists. 2009-2010 influenza season assessment and treatment for pregnant women with May 15, 2010 Postgraduate Obstetrics & Gynecology 5 PGO09.qxd:Layout 1 3/31/10 2:20 PM Page 5
  • 6. influenza-like illness. Available at: www.acog.org/departments/resource Center/2009H1N1TriageTreatment.pdf. 18. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation, 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. 19. Centers for Disease Control and Prevention. 2009 H1N1 flu (swine flu) and feeding your baby: what parents should know. Available at: www.cdc/gov/h1n1flu/infantfeeding.htm. 20. Centers for Disease Control and Prevention. H1N1 flu: infection control. Available at: www.cdc/gov/h1n1flu/infectioncontrol/. 21. ACOG Committee on Obstetric Practice. ACOG committee opinion num- ber 305, November 2004. Influenza vaccination and treatment during pregnancy. Obstet Gynecol 2004;104:1125-1126. 22. Tamma PD, Ault KA, del Rio C, et al. Safety of influenza vaccination dur- ing pregnancy. Am J Obstet Gynecol 2009;201:547-552. 23. Centers for Disease Control and Prevention. Summary of 2009 monova- lent H1N1 influenza vaccine data: vaccine adverse event reporting sys- tem. Data through January 15, 2010. Available at: http://vaers.hhs.gov/ resources/2010H1N1Summary_Jan08.pdf. Postgraduate Obstetrics & Gynecology May 15, 2010 6 1. Influenza vaccination is safe for use in pregnancy during A. the first trimester B. the second trimester C. the third trimester D. all trimesters 2. A pregnant patient calls the office at 4 p.m. on Friday after- noon reporting a sore throat and temperature of 100.5°F. You should A. ask her to take acetaminophen and call back if symp- toms worsen B. call in an antiviral medication prescription to the local pharmacy and ask her to call your office if she feels worse C. advise her to go to the nearest emergency department immediately 3. A patient with active H1N1 influenza infection should be advised to discard breast milk while taking oseltamivir. A. True B. False 4. Which of the following medications should be prescribed for H1N1 influenza infection in a patient who is 23 weeks preg- nant and manages asthma with chronic corticosteroids? A. Oseltamivir B. Zanamivir C. Both of the above D. Neither of the above 5. A pregnant health care worker on day 3 of oseltamivir use has been afebrile for 48 hours. She may return to work A. at this time B. after completion of the 5-day course of antiviral medication C. 72 hours after being afebrile and without symptoms D. 7 days after resolution of symptoms 6. At the first prenatal visit, a patient reports that she has not yet received either an H1N1 influenza vaccine or the sea- sonal influenza vaccine. You should A. administer the H1N1 vaccine and have her return in 1 week for her seasonal influenza vaccine B. administer the seasonal influenza vaccine and have her return in 1 week for her H1N1 vaccine C. administer both vaccinations at this visit but on con- tralateral extremities D. explain that as it is February and past the peak time for influenza infection this year, she does not need either vaccination 7. You are seeing an otherwise healthy pregnant patient in the clinic who you suspect has H1N1 influenza. Which one of the following regimens should you prescribe? A. Oseltamivir 75 mg twice daily for 5 days B. Oseltamivir 75 mg once daily for 10 days C. Tylenol 650 mg PO every 6 hours as needed for fever D. A and C 8. A patient calls the office 1 week postpartum to report fever and cough. You tell her A. she needs to be treated for H1N1 influenza, as the immediate postpartum period is associated with high risk of complications B. she is no longer pregnant and thus no longer needs antiviral medication, but she should call the office if her symptoms worsen C. she should see her internist or family physician, as you only evaluate pregnant patients 9. Fever is invariably present at some point in the course of disease in a patient with H1N1 influenza illness. A. True B. False 10. A pregnant hospital employee escorts a patient infected with H1N1 from the emergency department to an inpatient unit. She then reads in the newspaper of the potential dan- gers of H1N1 influenza during pregnancy and calls you to advise her. You tell her A. she needs to initiate antiviral therapy immediately B. the CDC has defined close contact with an infected patient, and this encounter does not constitute such an encounter C. she should stay home from work tomorrow to see whether symptoms of influenza arise, and if they do, to call your office To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed answer form, answering at least seven of the 10 quiz questions correctly.Select the best answer and use a blue or black pen to completely fill in the corresponding box on the enclosed answer form. Please indicate any name and address changes directly on the answer form.If your name and address do not appear on the answer form, please print that information in the blank space at the top left of the page. Make a photocopy of the completed answer form for your own files and mail the original answer form in the enclosed postage-paid business reply envelope.Your answer form must be received by Lippincott CME Institute by May 14, 2011. Only two entries will be considered for credit. At the end of each quarter, all CME participants will receive individual issue certificates for their CME participation in that quarter.Participants will receive CME certificates quarterly in April, July, October, and the fourth quarter in January of the following year. For more information, call (800) 787-8981. Online quiz instructions: To take the quiz online, go to http://cme.LWWnewsletters.com, and enter your username and password. Your username will be the letters LWW (case sensitive) followed by the 12-digit account number on your mailing label.You may also find your account number on the paper answer form mailed with your issue.Your password will be 1234; this password may not be changed. Follow the instructions on the site.You may print your official certificate immediately. Please note: Lippincott CME Institute will not mail certificates to online participants. Online quizzes expire at 11:59 pm Pacific Standard Time on the due date. CME QUIZ: Volume 30, Number 9 PGO09.qxd:Layout 1 3/31/10 2:20 PM Page 6