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.

Author Keywords: measles; infection; abortion; immunoglobulin; congenital

Article Outline

1. Introduction

2. Case reports

2.1. Case 1: a 26 year-old woman, gravida1, para0

2.2. Case 2: a 20 year-old woman, gravida1 para2

2.3. Case 3: a 23 year-old woman, gravida1, para1

2.4. Case 4: a 23 year-old woman, gravida0 para0

2.5. Case 5: a 32 year-old woman, gravida1 para1

2.6. Case 6: a 30 year-old woman, gravida0, para0, biconus uteri

2.7. Case 7: a 32 year-old woman, gravida2 para1

2.8. Case 8: a 26 year-old woman, gravida2 para2

3. Discussion

Acknowledgements

References

1. Introduction

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, 70–80% 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 (60–70/min), hypoxia (SapO2, 90–92), 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. 217–226.

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 Gynecol 164 (1991), pp. 107–108.

4. S.J. Stern and J.S. Greenspoon, Rubeola during pregnancy. Obstet Gynecol 78 (1991), pp. 925–928.

5. J.E. Eberhar-Phillips, P.D. Frederick, R.C. Baron and L. Mascola, Measles in pregnancy: a descriptive study of 58 cases. Obstet Gynecol 82 (1993), pp. 797–801.

6. M. Kamaci, C.G. Zorlu and A. Belhan, Measles in pregnancy. Acta Obstet Gynecol Scand 75 (1996), pp. 307–308.

7. E. Ali and N.M. Alber, Measles in pregnancy: maternal morbidity and perinatal outcome. Int J Gynecol Obstet 59 (1997), pp. 109–113.

8. M. Ohyama, T. Fukui, Y. Tanaka et al., Measles virus infection in the placenta of monozygotic twin. Mod Pathol 14 (2001), pp. 1300–1303.

9. J.P. Greenhill, Acute (extragenital) infections in pregnancy, labor, and the puerperium. Am J Obstet Gynecol 25 (1933), pp. 760–772.

10. I. Dyer, Measles complicating pregnancy. Report of twenty-four cases with three instances of congenital measles. South Med J 33 (1940), pp. 601–604.

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 Scand 144 (1953), pp. 430–449.

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. 375–427.

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 Med 274 (1966), pp. 768–771.

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. JAMA 197 (1966), pp. 680–684.

15. M. Siegel, Congenital malformations following chicken pox, measles, mumps, and hepatitis. Results of a cohort study. JAMA 226 (1973), pp. 1521–1524.

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