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Makiko Egashira Chibaa, Masatoshi Saitoa, Nobuaki Suzukib,
Yoshinobu Hondac and Nobuo Yaegashi, , a
a Department of Obstetrics and Gynecology, Tohoku University School
of Medicine, Sendai, Japan b Suzuki Maternal Clinic, Iwaki, Japan c Department of Pediatrics, Iwaki Kyoritu Hospital, Iwaki, Japan
Available online 7 May 2003.
Abstract
Objectives: Measles during pregnancy has deleterious effects on
both the perinatal outcome and the mother. However, in-depth knowledge
about gestational measles is lacking. The objectives of this study were to
describe the clinical course of eight cases of gestational measles and to
study the effect of measles and pregnancy on each other.
Methods: From late 2000 to early 2001, we experienced a measles
outbreak with eight infected pregnant women. The clinical course of each
case is described in detail.
Result: Three of the four cases before 24 weeks of gestation
ended in spontaneous abortion or stillbirth. The clinical course of the
three abortions and stillbirth were singular because of the sudden onset
of the abortion and the spontaneous pregnancy termination. In contrast,
the four pregnancies after 25 weeks of gestation ended in live-term
delivery and two out of the four neonates were diagnosed with congenital
measles. There was no maternal death, instead two pneumonia cases and one
hemorrhagic shock case.
Conclusions: Gestational measles may potentially damage the
fetus and is one of the serious complications that can occur during
pregnancy.
Before the nationwide measles vaccination program, most people
contracted measles before reaching adulthood and it was unusual to see a
measles infection during pregnancy. After the initiation of the measles
vaccine program, measles dramatically decreased, but ironically more
adults now have measles infections. In Japan, the measles vaccine has been
incorporated in the national immunization program since 1978.
Approximately, 80% of all children are immunized before 90 months of age.[1] Consequently, 7080% of Japanese women of reproductive
age have antibodies to measles, and approximately 100,000 cases occur each
year in Japan, which has a population of 120 million. These
epidemiological changes increase the chance of measles infection in
pregnant women and the number of infections in women of reproductive age
is estimated to be 1000 per year in Japan.
Measles during pregnancy has a deleterious effect on the perinatal
outcome, which is characterized by frequent abortions, premature labor,
and increased risk of fetal/neonatal loss. The incidence of maternal death
and other complications from measles during pregnancy is higher than
expected for pregnant women. However, information about measles during
pregnancy is lacking.[2]
From late 2000 to early 2001 in the Iwaki district in northeastern
Japan, with a population of approximately 600,000, a measles outbreak
occurred. Eight infected pregnant women visited our hospital. The
objectives of this study were to describe the clinical course of each case
and to study the effect of measles and pregnancy on each other.
2. Case reports
2.1. Case 1: a 26 year-old woman, gravida1, para0
At 13 weeks 4 days of gestation, she complained of fever. At 14 weeks 3
days of gestation, she was diagnosed with measles with the appearance of
Koplik spots and the characteristic maculopapular rash. With a complaint
of dyspnea, she was hospitalized in the obstetrics department of the Iwaki
Kyoritu Hospital. Although she lacked lower abdominal pain and discomfort
that would suggest a potential abortion, suddenly she vaginally bled with
clots and was diagnosed with spontaneous abortion the evening of her
admission. Her clinical course after the abortion was uneventful. Serum
obtained on admission day was positive ELISA for anti-measles IgG and IgM.
2.2. Case 2: a 20 year-old woman, gravida1 para2
At 16 weeks and 3 days of gestation, she had a high fever and was
hospitalized. Three days later, she was diagnosed with measles with the
appearance of Koplik spots and the characteristic maculopapular rash. She
did not feel lower abdominal pain or discomfort, which would suggest the
threat of abortion as in case 1, so she returned home. However, at 17
weeks and 1 day, suddenly she vaginally bled at home and was transferred
to the obstetric department in an ambulance because of spontaneous
abortion and hemorrhagic shock. Adequate treatments against shock and
abortion were performed and her clinical course after the abortion was
uneventful. Serum obtained on admission was positive by ELISA for
anti-measles IgG and IgM.
2.3. Case 3: a 23 year-old woman, gravida1, para1
Two weeks before her presentation, her child developed measles. On 24
weeks of gestation, she complained of fever. Three days later, she was
diagnosed with measles with the appearance of Koplik spots and the
characteristic maculopapular rash. She was not hospitalized due to a good
general condition and did not feel lower abdominal pain and discomfort.
However, at 24 weeks and 6 days, suddenly she delivered at home without
any prodromal labor symptoms. The stillborn baby, 650 gm, was covered with
the intact amniotic membrane and fluid. She and the baby were transferred
by ambulance to the obstetric department. Her clinical course after the
delivery was uneventful with adequate treatments. Serum obtained on the
second day after admission was positive by ELISA for anti-measles IgG and
IgM. Titers of anti-measles IgG and IgM in the baby serum were both
negative. No characteristic signs of measles infection were seen on the
baby's skin surface.
2.4. Case 4: a 23 year-old woman, gravida0 para0
At 34 weeks and 3 days of gestation, she complained of fever. At 34
weeks and 6 days of gestation, she was diagnosed with measles with the
appearance of Koplik spots and the characteristic maculopapular rash. She
was hospitalized for measles in the obstetric department for two weeks.
Serum obtained on the second day of admission was positive by ELISA for
anti-measles IgG and IgM. At 38 weeks and 3 days, her labor pain began.
She underwent a cesarean section because of labor dystocia. The baby was
2955 gm, with an Apgar score of 8 for 1 min and 9 for 5 min, without any
signs of measles infection and anomaly. Immediately, immunoglobulin was
prophylactically injected into the baby. Anti-measles IgG was positive in
the umbilical cord blood, but IgM was negative. No characteristic signs of
measles infection were seen on the baby's skin surface. We believe that
this baby was not infected by the measles virus in utero.
2.5. Case 5: a 32 year-old woman, gravida1 para1
At 13 weeks and 6 days of gestation, she was diagnosed with measles
with the appearance of Koplik spots and the characteristic maculopapular
rash, and admitted to obstetrics for eight days. Serum obtained five days
after admission was positive by ELISA for anti-measles IgG and IgM. After
recovery, her pregnancy course was uneventful until labor started. She
delivered a normal healthy baby at term. The baby had no signs of
congenital measles infection and the general condition was fine. Umbilical
cord blood was not examined for measles antibodies, but immunoglobulin was
prophylactically injected into the baby as a precaution.
2.6. Case 6: a 30 year-old woman, gravida0, para0, biconus uteri
At 34 weeks and 3 days of gestation, she complained of catarrhal
symptoms and was admitted to obstetrics. At 34 weeks and 5 days of
gestation, she was diagnosed with measles with the appearance of Koplik
spots and the characteristic maculopapular rash. Anti-measle antibodies in
her serum withdrawn on admission were positive for IgM and negative for
IgG. Ritodrine was administered when complaints of premature labor
surfaced. At 37 weeks and 1 day of gestation, she was discharged from the
hospital, but three days later returned because of a premature membrane
rupture. She underwent a cesarean section because of fetal distress. The
baby was 2290 gm with an Apgar score of 8 at 1 min and 9 at 5 min. The
baby showed no signs of congenital measles infection and anomaly. The
general condition after birth was uneventful. Immediately, immunoglobulin
was prophylactically injected into the baby. Anti-measles IgG and IgM in
the cord blood were present. We thought that the baby was infected by the
measles virus in utero, but recovered completely before birth.
2.7. Case 7: a 32 year-old woman, gravida2 para1
At 38 weeks and 6 days of gestation, she complained of catarrhal
symptoms. On 39 weeks and 3 days of gestation, the general rash appeared
and she was transferred by an ambulance to the obstetric department. She
was diagnosed with measles with the appearance of Koplik spots and the
characteristic maculopapular rash. Within a couple of hours after her
arrival, she delivered a 3460 g infant with an Apgar score of 8 at 1 min
and 9 at 5 min. The infant had no anomaly, but had a fever (38.5 °C),
tachypnea (6070/min), hypoxia (SapO2, 9092), the maculopapular rash on
the face and the chest, and Koplic-like spots. The pediatricians did not
diagnose congenital measles at this point, but immunoglobulin was
prophylactically injected. On the second day after birth, the exanthema
disappeared and the body temperature returned to normal. Three days after
birth, tachypnea disappeared and the general condition remained good
afterwards. Anti-measles IgG and IgM from maternal serum obtained on
delivery day were both positive. Twenty-two days after birth, anti-measles
IgG and IgM were both positive in the baby's serum. Therefore, the baby
was diagnosed with congenital measles.
2.8. Case 8: a 26 year-old woman, gravida2 para2
At 38 weeks of gestation, her daughter had measles. At 39 weeks and 3
days of gestation, she complained of catarrhal symptoms. At 40 weeks and 1
day, she was diagnosed with measles with the appearance of Koplik spots
and the characteristic maculopapular rash. At 40 weeks and 4 days of
gestation, she spontaneously delivered a 2690 gm baby with an Apgar score
of 8 at 1 min and 10 at 5 min. The baby had a general cyanostic appearance
two days after birth but no exanthema, which would suggest congenital
measles. Immunoglobulin was prophylactically injected two days after
birth. The baby was diagnosed with Tetralogy of Fallot and subsequently
entered the NICU. Three days after birth, maculopapular exanthema appeared
on the extremities and ran a febrile course. Nine days after birth the
fever disappeared, and 11 days after birth the exanthema faded away. The
baby's serum IgG and IgM antibodies to measles were both negative two days
after birth and both turned positive 13 days after birth. The baby was
diagnosed with congenital measles, but the general condition was fine
following discharge.
3. Discussion
In these eight cases, three out of four pregnancies with measles
infections before 24 weeks of gestation ended in spontaneous abortion or
stillbirth. In contrast, the four pregnancies with measles infections
after 25 weeks of gestation ended in live-term delivery. Interestingly,
the clinical course of the three abortions and stillbirth were singular
because of the sudden onset and spontaneous termination of pregnancy.
Atmar et al. performed a literature review of measles during pregnancy
from 1646 to 1990.[2] Accordingly, we performed a
literature review published since 1990, and summarized the data in
Table I.[2, 3,
4, 5, 6,
7 and 8] This review showed that
measles had deleterious effects on pregnancy as demonstrated by the
increased number of abortions, stillbirths, and pre-term labors, similar
to the results of the eight cases presented in this study.
Table I. Data from literature review of cases of measles during
pregnancy, published since 1990
(28K)
sp-ab, spontaneous abortion (expelled at 20 weeks or less of
gestation); IUFD, intrauterine fetal death.
Infants with measles at birth or within the first ten days of life are
diagnosed congenital. In 1904, Nouvat et al. reported that congenital
measles was present in 25% of 84 gestational measles cases, 28% of which
ended in death.[9] However, such a high mortality of
the fetus or neonate by congenital measles was not reported in the
following papers: 24 gestational cases, [10] 83 case
reviews, [11] 58 gestational cases, [5]
and 40 cases. [7] The low incidence in the recent
series may reflect the effects of prophylactic immunoglobulin. Our two
cases with a mild clinical course of congenital measles may encourage the
prophylactic use of immunoglobulin to all suspicious infants, as
recommended by Gershon. [12] However, extremely low
morbidity of recent congenital measles makes it difficult to evaluate the
efficacy of prophylactic immunoglobulin injection to infants with
suspicious congenital measles infection. Interestingly, case 6 was
positive for anti-measles IgM, which indicated that intrauterine measles
infection occurred and the infant recovered prior to birth. Interestingly,
such a case has not been reported in congenital measles. The time between
maternal infection and the birth may be important, with the risk of
congenital measles possibly decreasing with an interval greater than three
weeks between the infection and actual birth.
Regarding the influence of gestational measles on the mother, the
incidence of maternal death and other severe complications from measles
during pregnancy may be higher.[5] In this study,
there was no maternal death, but two cases with pneumonia and one case of
hemorrhagic shock. Some researchers commented that severe maternal
complications and maternal death were reported in older publications. [13, 14 and 15]
Recent developments in the medical management of the mother may reduce the
risk of maternal mortality from gestational measles. However, from the
most recent eight reports since 1990 (Table I), three
maternal deaths out of 125 cases of gestational measles occurred. Measles
is one of the serious complications during pregnancy and information about
gestational measles is still lagging behind this serious and dangerous
complication for both mother and child.
Acknowledgements
This work was supported in part by a grant-in-aid from the Ministry of
Health and Welfare, Japan, and a grant-in-aid from the Ministry of
Education, Science and Culture, Japan.
References
1. Infectious diseases weekly report Japan,
Infectious diseases information center, Japan National Infection Research
Institute 2002.
2. R.L. Altmar, J.A. Englund and H. Hammill,
Complications of measles during pregnancy. Clin Infect Dis
14 (1992), pp. 217226.
3. K. Moroi, S. Saito, T. Kurata, T. Sata and M.
Yanagida, Fetal death associated with measles virus infection of the
placenta. Am J Obstet Gynecol164 (1991), pp.
107108.
4. S.J. Stern and J.S. Greenspoon, Rubeola during
pregnancy. Obstet Gynecol78 (1991), pp. 925928.
5. J.E. Eberhar-Phillips, P.D. Frederick, R.C.
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maternal morbidity and perinatal outcome. Int J Gynecol Obstet59 (1997), pp. 109113.
8. M. Ohyama, T. Fukui, Y. Tanaka et al.,
Measles virus infection in the placenta of monozygotic twin. Mod Pathol14 (2001), pp. 13001303.
9. J.P. Greenhill, Acute (extragenital) infections
in pregnancy, labor, and the puerperium. Am J Obstet Gynecol25 (1933), pp. 760772.
10. I. Dyer, Measles complicating pregnancy.
Report of twenty-four cases with three instances of congenital measles.
South Med J33 (1940), pp. 601604.
11. P.E. Christensen, H. Schmidt, H.O. Bang, V.
Andersen, B. Jordal and O. Jensen, An epidemic of measles in Southern
Greenland, 1951. Measles in virgin soil. II. The epidemic proper. Acta
Med Scand144 (1953), pp. 430449.
12. A.A. Gershon, Chickenpox, measles and mumps.
In: J.S. Remington and J.O. Klein, Editors, Infection diseases of the
fetus and newborn infant (5th edn ed.),, WB Saunders, Philadelphia
(2001), pp. 375427.
13. M. Siegel, H.T. Fuerst and N.S. Peress,
Comparative fetal mortality in maternal virus diseases. A prospective
study on rubella, measles, mumps, chicken pox and hepatitis. N Engl J
Med274 (1966), pp. 768771.
14. M. Siegel and H.T. Fuerst, Low birth weight
and maternal virus diseases. A prospective study of rubella, measles,
mumps, chicken pox, and hepatitis. JAMA197
(1966), pp. 680684.
15. M. Siegel, Congenital malformations following
chicken pox, measles, mumps, and hepatitis. Results of a cohort study.
JAMA226 (1973), pp. 15211524.
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