医薬品相互作用研究

Vol.36, No. 1（2012）

39（39）

医薬品相互作用研究
一
般論
文
36（1） 39-46 （2012）

Safety of Pandemic Inﬂuenza A (H1N1) 2009 Vaccination
during Pregnancy in Japan
Hiroshi KARIKOMI1,2), Tomoya SAKURADA1), Sachiko OHDE3), Kazumi GOTOH2),
Eriko KOBAYASHI1), Nobunori SATOH1)
1)

Department of Clinical Education and Research, Graduate School of Pharmaceutical Sciences, Chiba University
2)
Department of Pharmacy, St. Lukeʼs International Hospital
3)
Center for Clinical Epidemiology, St. Lukeʼs Life Science Institute(Received May 17, 2012；Accepted June 20, 2012)

The U.S. Center for Disease Control and Prevention (CDC) and American College of Obstetricians andGynecologists (ACOG) have recommended that the inﬂuenza vaccination be given to pregnant women
who are in the high-risk group of inﬂuenza infection. However, because to date there is little data on
the inﬂuenza vaccine use in pregnant women and the safety for pregnant women in Japan has not been
well studied, the inﬂuenza vaccination during pregnancy has not been recommended. However, following reports of severe cases of inﬂuenza, including death, among pregnant women in other countries
during the inﬂuenza A (H1N1) pandemic in 2009, the limitations regarding the vaccination for
pregnant women listed in the Japanese inﬂuenza vaccine package insert have been relaxed, and theJapanese government has expressed the recommendation for pregnant women to have the inﬂuenza A(H1N1) 2009 vaccine. We investigated 416 pregnant women who were vaccinated by the inﬂuenza A(H1N1) 2009 vaccine, and 716 non-vaccinated pregnant women from 2009 through 2010, in order toevaluate the safety of the inﬂuenza A (H1N1) 2009 vaccination during pregnancy in Japan. No signiﬁcant association between the inﬂuenza A (H1N1) 2009 vaccination and miscarriages, stillbirths, malformations, emergency cesareans, premature delivery or low birthweight infants was observed. Our study
indicated the safety of inﬂuenza A (H1N1)2009 vaccination during pregnancy.
Key Words: Inﬂuenza, Pregnancy, Inﬂuenza A (H1N1), Safety, Vaccination

Introduction

contact infection of a virus; it has been reported that

Examples of pandemics of inﬂuenza during thethe inﬂuenza infection during pregnancy is readily

20th century include Spanish ﬂu (H1N1) from 1918

elicits complications and is easily aggravated 3-5). The

to 1919, Asian ﬂu (H2N2) from 1957 to 1958, andinﬂuenza pandemic of swine origin, which stemmed

Hong Kong ﬂu (H3N2) from 1968 to 1969. It wasfrom Mexico in the spring of 2009, quickly spreadreported that the mortality rate of pregnant women

worldwide, just as the inﬂuenza pandemics which

was higher than that of the general population in thehave occurred in the past. At the outbreak of

1,2). Inﬂuenza

pandemic inﬂuenza A (H1N1) 2009 in Japan, there

is a respiratory tract infection spread by droplets

were more than 20 million inﬂuenza A (H1N1) 2009

from the respiratory tract of the infected patient andpatients. However, it is noteworthy that only 198

pandemics of Spanish ﬂu and Asian ﬂu

Department of Clinical Education and Research, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku,
Chiba 260-8675, Japan2）
Department of Pharmacy, St. Lukeʼs International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan
3）
Center for Clinical Epidemiology, St. Lukeʼs Life Science Institute, 10-1 Akashi-cho, Chuo-ku, Tokyo 104-0044, Japan
Tomoya SAKURADA, Department of Clinical Education and Research, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1
Inohana, Chuo-ku, Chiba 260-8675, Japan.
e-mail: sakurat@faculty.chiba-u.jp1）

40（40）

医薬品相互作用研究

Vol.36, No. 1（2012）

death cases have been reported nationwide and nocountries 20), inﬂuenza vaccination during pregnancy

death case among pregnant women was reported inin Japan has not been recommended. However,

6)

Japan . Although there was no death and very few

following reports of death and serious cases ofserious cases among inﬂuenza A (H1N1) 2009

inﬂuenza infection during pregnancy at the outbreak

infected pregnant women in Japan, cases of death orof pandemic inﬂuenza A (H1N1) in 2009, theserious cases among inﬂuenza A (H1N1) 2009

description in the package insert of the inﬂuenza

infected pregnant women were reported in othervaccines approved in Japan stating "Do not vaccinate

countries7-9). This may be because the prompt

in principle" was deleted and the description

administration of anti-inﬂuenza medicine in Japan inincluded the following new addition: "A small sample

the early stage following inﬂuenza diagnosis was

size study reported that the incidence of congenitaleﬀective.

anomaly in newborns of vaccinated pregnant women

It has been reported that oseltamivir and zanamivir

was not higher than that of the spontaneous

are eﬀective for the treatment of inﬂuenza A (H1N1)

incidence rate". Subsequently, the Japanese

2009 viruses 10) and both drugs are safe for the fetus

government policy regarding the inﬂuenza

with administration during pregnancy11). The

vaccination during pregnancy was changed aseﬀectiveness and safety of use during pregnancy ofment ioned above, and inﬂuenza vaccinat ion of

the anti-inﬂuenza drug have been reported, however

pregnant women is now strongly recommended evenprevention with inﬂuenza vaccination before an

in Japan 21) . However, very few reports are available

epidemic season is also very important to study.

on verifying the safety of the inﬂuenza vaccination

Since infect ious diseases can readily become

during pregnancy in Japan.

severe due to lowered immune response during

To evaluate the safety of the inﬂuenza A (H1N1)

pregnancy, the inﬂuenza vaccination is important to2009 vaccination during pregnancy in Japan, during

prevent inﬂuenza infection. In studies from many

the season from 2009 through 2010, we investigatedother countries on inﬂuenza vaccination during

pregnancy outcome of vaccinated pregnant womenp r e g n a n c y, t h e i n ﬂ u e n z a v a c c i n a t i o n d u r i n g

and non-vaccinated pregnant women.

pregnancy has been shown to have no harmful
eﬀects on fetal development and delivery of thenewborn, and the safety and beneﬁt of an inﬂuenza

Subjects and Methods
１. Subjects

vaccination during pregnancy have been

The study population included all pregnant women

evaluated 12-17). Therefore, the U.S. Center for Disease

and newborns delivered in St. Luke's International

Control and Prevention (CDC) and American College

Hospital (Tokyo, Japan) during October 1, 2009, toof Obstetricians and Gynecolog ists (ACOG) has

September 30, 2010 (n=1157). A total of 1132 cases

recommended inﬂuenza vaccination to pregnant

were investigated; 24 sets of twins and one set of

women who are one of the high-risk g roups of

triplets were excluded from the study.

inﬂuenza infection 18,19). On the other hand, inﬂuenza
vaccination for pregnant women has not been

２. Study design

recommended in Japan. This is because 1) there are

We performed a retrospective electronic chart

few data available on the safety of inﬂuenza

search from October 1, 2009, to September 30,

vaccinat ion during pregnancy, and 2) the

2010, at St. Luke's International Hospital in Tokyo,

description in the package leaﬂet of the JapaneseJapan.

inﬂuenza vaccine states: "Vaccination of pregnant
women or women who may be pregnant is,

３. Methods

principally, not recommended since the safety of

The age at delivery, clinical history, race, andvaccination during pregnancy has not been

medicine use during pregnancy were used as basic

established". Similarly, since there are few studies on

informat ion. Among the invest ig ated pregnant

the inﬂuenza vaccine use in pregnant women andwomen, the pregnant women who received thesince inﬂuenza vaccination during pregnancy could

inﬂuenza A (H1N1) 2009 vaccine during pregnancy

not be considered securely safe in many European

were deﬁned as the vaccinated group and the医薬品相互作用研究

Vol.36, No. 1（2012）41（41）

pregnant women who did not receive the inﬂuenza A

used carbamazepine for epilepsy treatment during(H1N1) 2009 vaccine during pregnancy were deﬁned

the entire pregnancy period.

as the non-vaccinated group. Vaccination time andthe days of pregnancy at the time of vaccinationn (%)
Age at delivery (years)

were investigated in the inﬂuenza A (H1N1) 200920 - 24

7 (0.6)

vaccinated group. We investigated the presence of

25 - 29

95 (8.4)

30 - 34449 (39.7)

35 - 39386 (34.1)

40

195 (17.2)

Asthma56 (5.0)

inﬂuenza A (H1N1) 2009 vaccination during
pregnancy and the following factors: age at delivery,
gestation length, inﬂuenza infection during

Clinical history

pregnancy, the anti-inﬂuenza medicine
administrat ion during pregnancy, miscarriage,
stillbirth, malformation, emergency cesarean section,

Hypertension

5 (0.4)

Diabetes

2 (0.2)

Japanese

1101 (97.3)

Others31 (2.7)

Racepremature delivery (under 37 weeks), birthweightand pregnancy-induced hypertension. The inﬂuenza
A (H1N1) 2009 vaccine administered in this study

Table 1 : Characteristics of 1132 pregnant women

w a s " A I n ﬂ u e n z a H A Va c c i n e : H 1 N 1 ( K i t a s a t oInstitute)" (without any adjuvants or preservatives).

２ . Number of vaccination given monthly and averagedays of pregnancy at the time of vaccination.

４. Statistical analyses

The vaccination against inﬂuenza A (H1N1) 2009

In order to compare subject characteristics andin the season from 2009 through 2010 was given to

pregnancy outcome between the inﬂuenza A (H1N1)

the subjects from November 2009 to March 2010;2009 vaccinated group and the non-vaccinated59.4% of all vaccination was given in November

group, a chi-square test for comparison of

2009. The average days of pregnancy at the time ofpercentage, a t-test and a one-way layout analysis ofvaccination against inﬂuenza A (H1N1) 2009 was

variance (ANOVA) for comparison of average value

179.9 days (Table 2).

was performed. If a statistically signiﬁcant result was
found in the one-way layout analysis of variance, a

Numbertest for the honestly signiﬁcant diﬀerence (HSD) of

Days of pregnancy

n (%)

mean ± SD

Tukey was performed. All of the statistics analyses

Nov-2009

247 (59.4)

202.0 ± 53.8

were performed using SPSS software version 18.0

Dec-2009

100 (24.1)

161.5 ± 58.0

(IBM Japan Ltd., Tokyo, Japan); the level of statisticalJan-2010

43 (10.3)

132.7 ± 43.6

signiﬁcance was p<0.05 in all the statistics analyses.

Feb-2010

18

(4.3)

119.2 ± 31.5

Mar-2010

8(1.9)

119.1 ± 32.2

416 (100.0)

179.9 ± 60.0

５. Ethical consideration
This study was approved by the Inst itut ional
Review Board (IRB) of St. Luke's International
Hospital.

Results
１. Characteristics of the subjects

Total

SD : standard deviation.
Table 2 : Number of vaccinations given monthly andaverage days of pregnancy at the time of vaccination

３ . Comparison of subjectʼs characteristics andpregnancy outcome between inﬂuenza A (H1N1)

Regarding age, 51.3% of the 1132 subjects were2009 vaccinated and non-vaccinated groups.

over 35 years old age at the time of delivery. There

There was no statistically signiﬁcant diﬀerence inwas nothing that was particularly frequent seen in

the average age at the t ime of delivery, thethe clinical history of the pregnant woman ofpercentage of the subjects who were 35 years andinvestigation, and 97.3% of the 1132 subjects wereolder at the time of delivery, the percentage of theJapanese (Table 1).

anamnesis and the percentage of the race between

As for the teratogenic agent use during pregnancy,
only one subject (vaccinated group, no malformation)

the inﬂuenza A (H1N1) 2009 vaccinated group andthe non-vaccinated group.

42（42）

医薬品相互作用研究

Vol.36, No. 1（2012）

The average delivery days was signiﬁcantly longer

４ . Comparison of subjectʼs characteristics andin the inﬂuenza A (H1N1) 2009 vaccinated grouppregnancy outcome according to the term ofthan in the non-vaccinated group (p<0.05) (Table 3).

vaccination in the inﬂuenza A (H1N1) 2009

No statistically signiﬁcant diﬀerence was foundvaccinated group.

among both groups regarding the rate of inﬂuenza

By the term of vaccination in inﬂuenza A (H1N1)

i n f e c t i o n d u r i n g p r e g n a n c y, t h e a n t i - i n ﬂ u e n z a

2009 vaccinated group (n=416), there was no

medicine administrat ion during pregnancy,

statistically signiﬁcant diﬀerence in the average age

miscarriage, stillbirth, malformation, emergency

at the time of delivery and the percentage of thecesarean sect ion, premature delivery, low

subjects who were 35 and older at the t ime ofbirthweight infants, and pregnancy-induced

delivery. The average delivery days for the subjects

hypertension. An average birthweight, in the

who were vaccinated during the third trimester wasinﬂuenza A (H1N1) 2009 vaccinated group was

signiﬁcantly longer than in the subjects who weresigniﬁcantly heavier than that in a non-vaccinatedvaccinated during the second trimester (p<0.05)

group (p<0.05) (Table 4). The anti-inﬂuenza medicine(Table 5). No statistically signiﬁcant diﬀerence waswhich was administered to subjects in both groups

found according to the term of vaccination in thewas Oseltamivir only.

rate of inﬂuenza infection during pregnancy, theanti-inﬂuenza medicine administration during
pregnancy st illbirth, malformat ion, emergency
cesarean section, low birthweight infant,Age at delivery (years, mean ± SD)
Age at delivery

35 (n (%))

Gestation length (days, mean ± SD)
Clinical history (n (%))

Vaccinated group

Non-vaccinated group(n = 416)(n = 716)

35.6 ± 4.0

35.4 ± 4.4

P value
0.469

211 (50.7)

370 (51.7)

0.757

276.8 ± 10.7

274.5 ± 13.4

0.030

22 (5.3)

34 (4.7)

0.686

AsthmaHypertension

3 (0.7)2 (0.3)0.280

Diabetes

1 (0.2)1 (0.1)

0.697

Japanese

407 (97.8)

694 (96.9)

0.366

Race (n (%))
SD : standard deviation.
Table 3 : Characteristics of pregnant women in vaccinated and non-vaccinated groups

Vaccinated group

Non-vaccinated group(n = 416)(n = 716)

Influenza infection during pregnancy (n (%))

6 (1.4)9 (1.3)Anti-influenza medicine administration during pregnancy (n (%))

10 (2.4)

12 (1.7)

0.392

Miscarriage (n (%))

2 (0.5)6 (0.8)

0.489
0.108

P value
0.793

Stillbirth (n (%))

2 (0.5)

11 (1.5)

Malformation (n (%))

9 (2.2)14 (2.0)

0.811

Emergency cesarean section (n (%))

41 (9.9)93 (13.0)0.116

Premature delivery (<37 weeks, n (%))

18 (4.3)

48 (6.7)

0.100

3017.3 ± 498.2

2916.2 ± 618.4

0.005

Low birthweight infants (<2500g, n (%))

43 (10.3)

91 (12.7)

0.100

Pregnancy-induced hypertension (n (%))

14 (3.4)

26 (3.6)

0.815

Birthweight (g, mean ± SD)

SD : standard deviation.
Table 4 : Pregnancy outcome in vaccinated and non-vaccinated groups

医薬品相互作用研究

Vol.36, No. 1（2012）

43（43）

pregnancy-induced hypertension and the average

Discussion

birthweight. There was a statistically signiﬁcant

In order to evaluate the safety of the inﬂuenza A

diﬀerence in the rate of miscarriage and premature(H1N1) 2009 vaccination during pregnancy in Japan,

delivery (p<0.05) (Table 6).

during the season from 2009 through 2010, we

The types of malformations in subjects ofinvestigated the pregnancy outcome of vaccinatedinvestigation were as follows in the vaccinated grouppregnant women and non-vaccinated pregnant

and the non-vaccinated group. The malformations inwomen. In this investigation, regarding the average

the inﬂuenza A (H1N1) 2009 vaccinated group wered a y s t o d e l i ve r y, t h e i n ﬂ u e n z a A ( H 1 N 1 ) 2 0 0 9a case of right accessory ear, vulvar hypertrophy,

vaccinated group was signiﬁcantly longer than thatblack nevus, 21 trisomy, hypospadias, aproctia, backof the non-vaccinated group. As for averageof the head subcutaneous mass, syndactylism, and 18

birthweight, the babies of the inﬂuenza A (H1N1)

trisomy. The malformations in the non-vaccinated2009 vaccinated group were signiﬁcantly heavier

group were two cases of cleft lip and palate, a case ofthan those of the non-vaccinated group. Regarding

paternal uniparental disomy for chromosome 14, 21

the timing of vaccination in inﬂuenza A (H1N1) 2009

trisomy, mandibular congenital tooth, hemangioma,

vaccinated group, the average delivery days in thewalleye, 18 trisomy, black nevus, spina biﬁda,

subjects who were vaccinated during the third

anencephaly, auricle hypoplasia, hypospadias, andtrimester was signiﬁcantly longer than that in theright accessory ear. All the subjects whose babies

subjects who were vaccinated during the second

had any malformation in the inﬂuenza A (H1N1)

trimester. However, the average delivery days were2009 vaccinated group had inﬂuenza vaccination inwithin the term delivery in the comparison between

the second trimester or later, except for one subject

the vaccination group and non-vaccination group and(inﬂuenza vaccination at 88 days of pregnancy)in the comparison of vaccination term in thewhose baby had a hypospadias.

vaccination group.
Regarding the ratio of the low birthweight infants,
no statistically signiﬁcant diﬀerence was found in the

Age at delivery (years, mean ± SD)
Age at delivery

35 (n (%))

Gestation length (days, mean ± SD)

1st trimester

2nd trimester

3rd trimester(n = 43)(n = 178)(n = 195)35.5 ± 4.1

35.8 ± 4.1

35.2 ± 3.8

P value0.364

25 (58.1)

91 (51.1)

95 (48.7)

0.530

275.3 ± 15.4

275.5 ± 9.7

278.2 ± 10.3

0.038

SD : standard deviation.

p=0.045
Table 5 : Characteristics of pregnant women according to the vaccination term

1st trimester

2nd trimester

3rd trimester(n = 43)(n = 178)(n = 195)

P value

Influenza infection during pregnancy (n (%))

0 (0.0)4 (2.2)2 (1.0)Anti-influenza medicine administration during pregnancy (n (%))

0 (0.0)5 (2.8)5 (2.6)

0.547

Miscarriage (n (%))

2 (4.7)0 (0.0)0 (0.0)<0.001

0.432

Stillbirth (n (%))

0 (0.0)2 (1.1)0 (0.0)0.261

Malformation (n (%))

1 (2.3)4 (2.2)4 (2.1)

0.989

Emergency cesarean section (n (%))

2 (4.7)20 (11.2)

19 (9.7)

0.428

Premature delivery (<37 weeks, n (%))

5 (11.6)

7 (3.9)6 (3.1)

0.042

2893.7 ± 757.8

2995.2 ± 504.4

3064.6 ± 410.2

0.093

Low birthweight infants (<2500g, n (%))

6 (14.0)

21 (11.8)

16 (8.2)

0.373

Pregnancy-induced hypertension (n (%))

2 (4.7)6 (3.4)6 (3.1)0.874

Birthweight (g, mean ± SD)

SD : standard deviation.

Table 6 : Pregnancy outcome according to the vaccination term44（44）

医薬品相互作用研究

Vol.36, No. 1（2012）

comparison between the inﬂuenza A (H1N1) 2009were not statistically diﬀerent compared with thosevaccination group and the non-vaccination group andof the general population22). Moreover, thein the comparison of vaccination term in theprospective cohort study on the adjuvanted split

vaccination group. Therefore, there seemed to be

H1N1 (2009) vaccinat ion for pregnant women

little inﬂuence of the inﬂuenza A (H1N1) 2009

performed in U.K., reported that the risks ofvaccination on the weight of the newborn. Althoughspontaneous abortion, congenital anomalies, preterm

there were only a few cases, a statistically signiﬁcantdelivery, low birthweight neonates, and maternal

diﬀerence was observed in the rate of miscarriages

complications were not increased 23) . These reports

according to inoculation term; further investigationagree with the present report that vaccination

will be necessary on this matter.

against inﬂuenza A (H1N1) 2009 during pregnancy

A statistically signiﬁcant diﬀerence was foundregarding the ratio of premature deliveries, but two

does not raise the risk for the mother's body or the
newborn.

of the ﬁve premature deliveries seen in the ﬁrst

The report following an investigation in U.S. statedtrimester vaccination occurred withthat the ratio of preterm delivery and low

pregnancy-induced hypertension. Therefore, thebirthweight infants were high for the mothers who

possibility that pregnancy-induced hypertensiondelivered during hospitalization for inﬂuenza A

inﬂuenced the premature delivery should be(H1N1) 2009 infection in a season from 2009

considered, and the further investigation will bethrough 2010 24) . Therefore, the report emphasizednecessary.

that the vaccination of an inﬂuenza vaccine is

In the inﬂuenza A (H1N1) 2009 vaccinated groupimportant for pregnant women. Also in Japan, theand the non-vaccinated group, no statisticallypregnant women are targeted for priority of thesigniﬁcant diﬀerence was found regarding the ratio

vaccination as a high-risk group for inﬂuenza

of malformation, and also no speciﬁc malformation

infection 2 1 ) . In addition, there is a report which

type was seen. Furthermore, all of the eight subjects

describes the diﬀering policies and practices

whose babies had a malformation in the inﬂuenza A

regarding inﬂuenza vaccination for pregnant women(H1N1) 2009 vaccinated group had inﬂuenza

in each country in Europe25). The report has

vaccination in the second trimester or later, except

considered that the diﬀerences in pandemic

for one subject whose baby had a hypospadias andvaccination policy and practice from country to

who had inﬂuenza vaccination at 88 days ofcountry might explain the variation in perceptions ofpregnancy. Because there was no speciﬁc type of

vaccine eﬃcacy and safety, the vaccination campaign

malformation and teratogenesis did not concentrate

system, and operational issues related to vaccine

in the ﬁrst trimester which is highest teratogenic risk

manufacturing and procurement.

t e r m d u r i n g p r e g n a n c y, t h e p o s s i b i l i t y o f t h e

Regarding the campaign of the vaccination ofteratogenic risk rise to the fetus with inﬂuenza A

pregnant women in Japan, positive vaccination has(H1N1) 2009 vaccination during pregnancy iscome to be recommended by the announcement ofconsidered to be a low risk.

t h e M i n i s t r y o f H e a l t h , L a b o u r a n d We l f a r e i n

Although there are very few reports on inﬂuenza A

November 2009 which states that there is no report(H1N1) 2009 vaccination of pregnant women in

of increased risk of miscarriage or congenital

Japan other than the present report, there are someanomaly to date, even if an inﬂuenza vaccine isreports being published overseas. In France, duringadministered during pregnancy 21). The problem with

the inﬂuenza A (H1N1) pandemic in 2009, thethe operative aspect in conjunction with vaccine

inﬂuenza A (H1N1) 2009 vaccination for pregnant

production and the procurement in Japan, there has

women was recommended by the French Healthbeen an experience whereby the vaccine quantity ran

authorities as in Japan, and the vaccination was

low during the new inﬂuenza pandemic during 2009a d m i n i s t e r e d . I n t h e p r o s p e c t i ve s t u d y o n t h ethrough 2010. Therefore, the development of ainﬂuenza A (H1N1) 2009 vaccination for pregnant

stable supply system of vaccine will be indispensable

women performed in France, the risks of maternal

together w ith the accumulat ion of further safe

conditions, malformations and neonatal condition

information for vaccination promotion for pregnant

医薬品相互作用研究

women in Japan.

Vol.36, No. 1（2012）

45（45）

78, 1172-1175, 1959.

As for the safety of the inﬂuenza A (H1N1) 20093) Neuzil KM, Reed GW, Mitchel EF, Simonsen L,

vaccination during pregnancy, no increase in clinicalGriﬃn MR: Impact of inﬂuenza on acuterisk to pregnancy outcome with the vaccination was

cardiopulmonary hospitalization in pregnant

recognized by this investigation. However, as for the

women. Am J Epidemiol, 148, 1094-1102, 1998.

vaccination against inﬂuenza A (H1N1) 2009 during

4) Irving WL, James DK, Stephenson T, Laing P,

the ﬁrst trimester and the association of miscarriage

Jameson C, Oxford JS, Chakraverty P, Brown DW,

a n d p r e m a t u r e d e l i ve r y, f u r t h e r i nve s t i g a t i o nBoon AC, Zambon MC: Inﬂuenza virus infection

including a larger number of cases will be necessary.

in the second and third trimesters of pregnancy:

It is thought that this data might serve as a positivea clinical and seroepidemiological study. BJOG,

basis to support the safety of recommendation of107, 1282-1289, 2000.

vaccination for inﬂuenza A (H1N1) 2009 for

5) Hartert TV, Neuzil KM, Shintani AK, Mitchel EF Jr,

pregnant women, as the concept of positive

Snowden MS, Wood LB, Dittus RS, Griﬃn MR:

vaccination recommendation for pregnant women

Maternal morbidity and perinatal outcomes

had not been veriﬁed to date, due to the scarcity ofamong pregnant women with respiratory

data on safety for pregnant women. There are thehospitalizations during inﬂuenza season. Am J

following study limitations: this data is only from

Obstet Gynecol, 189, 1705-1712, 2003.

one establishment in Japan and delivery for women6) Sugaya N, Shinjoh M, Mitamura K, Takahashi T:

35 years old or older accounts for about half which

Very low pandemic inﬂuenza A(H1N1) 2009

makes for an unbalanced group toward the advanced

mortality associated with early neuraminidase

age side in comparison with 23.8% (2010) 2 6 ) of

inhibitor treatment in Japan: Analysis of 1000

delivery ratios in the Japanese whole 35 years old or

hospitalized children. J Infect, 63, 288-294,

older. The data on the safety of the inﬂuenza A

2011.

(H1N1) 2009 vaccination during pregnancy still is7) Jamieson DJ, Honein MA, Rasmussen SA, Williams

not suﬃcient, even including the overseas

JL, Swerdlow DL, Biggerstaﬀ MS, Lindstron S,

reporting 22,23,27,28) , therefore research including theLouie JK, Christ CM, Bohm SR, Fonseca VP, Ritger

accumulation of further future cases is necessary.

KA, Kuhles DJ, Eggers P, Bruce H, Davidson HA,
Lutterloh E, Harris ML, Burke C, Cocoros N,

Conclusions

Finelli L, MacFarlane KF, Shu B, Olsen SJ: H1N1

To evaluate the safety of the inﬂuenza A (H1N1)

2009 inﬂuenza virus infection during pregnancy

2009 vaccination during pregnancy in Japan, wein the USA. Lancet, 374:451-458, 2009.

invest ig ated pregnancy outcome of vaccinated8) Jain S, Kamimoto L, Bramley AM, Schmitz AM,

pregnant women and non-vaccinated pregnant

Benoit SR, Louie J, Sugerman DE, Druckenmiller

women.

JK, Ritger KA, Chugh R, Jasuja S, Deutscher M,

No signiﬁcant association was found between theChen S, Walker JD, Duchin JS, Lett S, Soliva S,

inﬂuenza A (H1N1) 2009 vaccination andWells EV, Swerdlow D, Uyeki TM, Fiore AE, Olsenmiscarriages, stillbirths, malformations, emergency

SJ, Fry AM, Bridges CB, Finelli L: Hospitalized

cesareans, premature delivery or low birthweightpatients with 2009 H1N1 inﬂuenza in the United

infants. The present study conﬁrmed the safety ofStates, April-June 2009. N Engl J Med, 361,

inﬂuenza A (H1N1)2009 vaccination during

1935-1944, 2009.

pregnancy.

9) Webb SA, Pettilä V, Seppelt I, Bellomo R, Bailey M,
Cooper DJ, Cret ikos M, Davies AR, Finfer S,

References

H a r r i g a n P W, H a r t G K , H o w e B , I r e d e l l J R ,1) Harris JW: Inﬂuenza occurring pregnant women: a

McArthur C, Mitchell I, Morrison S, Nichol AD,

statistical study of thirteen hundred and ﬁfty

Paterson DL, Peake S, Richards B, Stephens D,

cases. JAMA, 72, 978-980, 1919.

Turner A, Yung M: Critical care services and2) Freeman DW, Barno A: Death from Asian inﬂuenza
associated with pregnancy. Am J Obstet Gynecol,2009 H1N1 inﬂuenza in Australia and New
Zealand. N Engl J Med, 361, 1925-1934, 2009.

46（46）

医薬品相互作用研究

1 0 ) D a w o o d F S , J a i n S , F i n e l l i L , S h a w M W,
Lindstrom S, Garten RJ, Gubareva LV, Xu X,

Vol.36, No. 1（2012）

i n ﬂ u e n z a : W h y a n d w h y n o t ? . Va c c i n e , 2 9 ,7542-7550, 2011.

Bridges CB, Uyeki TM: Emergence of a novel21) Ministry of Health, Labour and Welfare, Japan.

swine-origin inﬂuenza A(H1N1) virus in humans.

Available at:http://www.mhlw.go.jp/kinkyu/

N Engl J Med, 360, 2605-2615, 2009.

kenkou/inﬂuenza/dl/infu091028-01.pdf

11) Tanaka T, Nakajima K, Murashima A,

Accessed Apr.6,2012.

Garcia-Bournissen F, Koren G, Ito S: Safety of22) Omon E, Damase-Michel C, Hurault-Delarue C,neuraminidase inhibitors against novel inﬂuenza

Lacroix I, Montastruc JL, Oustric S, Escourrou B:

A(H1N1) in pregnant and breastfeeding women.

Non-adjuvanted 2009 inﬂuenza A(H1N1)v

CMAJ, 181, 55-58, 2009.

vaccine in pregnant women: The results of a12) Deinard AS, Ogburn P Jr: A/NJ/8/76 Inﬂuenza
vaccination program: Eﬀects on maternal healthand pregnancy outcome. Am J Obstet Gynecol,
140, 240-245, 1981.

French prospective descriptive study. Vaccine,29, 9649-9654, 2011．
23) Tavares F, Nazareth I, Moneg al JS, Kolte I,
Verstraeten T, Bauchau V: Pregnancy and safety

1 3 ) Ye a g e r D P, To y E C , B a k e r B 3 r d : I n ﬂ u e n z aoutcomes in women vaccinated with anvaccination in pregnancy. Am J Perinatol, 16,

AS03-adjuvanted split virion H1N1(2009)283-286, 1999.

pandemic inﬂuenza vaccine during pregnancy: a14) Black SB, Shineﬁeld HR, France EK, Fireman BH,
P l a t t S T, S h a y D : E ﬀ e c t i ve n e s s o f i n ﬂ u e n z ap r o s p e c t i ve c o h o r t s t u d y. Va c c i n e , 2 9 ,6358-6365, 2011.

vaccine during pregnancy in preventing24) Centers for Disease Control and Prevention

hospitalizations and outpatient visits for(CDC): Maternal and infant outcomes among

respiratory illness in pregnant women and theirseverely ill pregnant and postpartum women

infants. Am J Perinatol, 21, 333-339, 2004.

with 2009 pandemic inﬂuenza A(H1N1)-United

1 5 ) M u n o z F M , G r e i s i n g e r A J, We h m a n e n OA ,States, April 2009-August 2010. MMWR

Mouzoon ME, Hoyle JC, Smith FA, Glezen WP:

Morbidity and Mortality Weekly Report, 60,

Safety of inﬂuenza vaccination during pregnancy.

1193-1196, 2011.

Am J Obstet Gynecol, 192, 1098-1106, 2005.

25) Luteijn JM, Dolk H, Marnoch GJ: Diﬀerences in16) Mak TK, Mangtani P, Leese J, Watson JM, Pfeifer

pandemic inﬂuenza vaccination policies for

D: Inﬂuenza vaccination in pregnancy: current

pregnant women in Europe. BMC Public Health,evidence and selected national policies. Lancet

11, 819, 2011.

Infect Dis, 8, 44-52, 2008.

26) Ministry of Health, Labour and Welfare, Japan.

17) Tamma PD, Ault KA, del Rio C, Steinhoﬀ MC,

Available at: http://www.mhlw.go.jp/toukei/

Halsey NA, Omer SB: Safety of inﬂuenza

saikin/hw/jinkou/kakutei10/dl/08̲h4.pdf

vaccinat ion during pregnancy. Am J Obstet
Gynecol, 201, 547-552, 2009.

Accessed Apr.6, 2012.
27) Moro PL, Broder K, Zheteyava Y, Revzina N,18) Harper SA, Fukuda K, Uyeki TM, Cox NJ, Bridges

Tepper N, Kissin D, Barash F, Arana J,Brantley

CB: Prevention and control of inﬂuenza:

MD, Ding H, Singleton JA, Walton K, Haber P,

Recommendations of the Advisory Committee on

Lewis P, Yue X, Destefano F, Vellozzi C: Adverse

Immunization Practices (ACIP). MMWR

events following administration to pregnant

Recommendations and Report, 53(Maywomen of inﬂuenza A(H1N1) 2009 monovalent(RR-6)),1-40, 2004.

vaccine reported to the Vaccine Adverse Event

19) ACOG Committee on Obstetric Practice: ACOG
committee opinion number 305, November

Reporting System. Am J Obstet Gynecol, 205,
473.e1-9, 2011.

2004. Inﬂuenza vaccination and treatment28) Huang WT, Chen WC, Teng HJ, Huang WI, Huang

during pregnancy. Obstet Gynecol, 104,

Y W, H s u C W, C h u a n g J H : A d v e r s e e v e n t s

1125-1126, 2004.

following pandemic A(H1N1) 2009 monovalent20) Blanchard-Rohner G, Siegrist CA: Vaccination

vaccines in pregnant women-Taiwan, November

during pregnancy to protect infants against

2009-August 2010. PLoS One, 6, e23049, 2011.