a Department of Virology, Haartman Institute,
b Public Health Sciences,
c Obstetrics and Gynaecology, University of Helsinki, Helsinki, Finland.
d Jorvi Hospital, Espoo, Finland.
e National Public Health Institute, Oulu, Finland.
Reprint requests to: Pia Mustakangas, Haartman Institute, Department of Virology, PO Box 21, FIN-00014 University of Helsinki, Finland.
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Abstract |
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Methods IgG and IgM antibodies to HCMV and IgG avidity were studied by enzyme-linked immunosorbent assay (ELISA) in three different socioeconomic areas (SEA) in the 912th week of pregnancy of 1088 consecutive mothers.
Results The overall IgG seropositivity was 70.7%, ranging from 60.9 to 76.4% in upper to lower SEA (P = 0.0004). The HCMV IgM seropositivity was 4.0%, ranging from 3.8% in the upper and intermediate SEA to 4.6% in the lower SEA. Serologically acute cases, defined by low avidity of IgG, represented 1.7% of the pregnancies in the upper SEA compared with 1.0 and 1.1% in the other two areas. In the lower SEA there were twice as many recurrent infections as in the others, 3.6 versus 1.7%. The low impact of age did not increase after elimination of the effects of SEA and parity. Miscarriages were associated neither with IgG nor with IgM positivity, although the percentage of 2 miscarriages was 8.8% in seronegative women compared with 11.2% and 13.6% in IgG- and IgM-positive women.
Conclusions Social environment seems to be the most powerful factor, predicting both IgG seroprevalence and recurrences during pregnancy.
Keywords Human cytomegalovirus, cohort, pregnancy, seroprevalence, socioeconomic
Accepted 1 December 1999
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Introduction |
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Patients |
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Methods |
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A serological test for syphilis serology (the TPHA test, Fujirebio, Inc., Tokyo, Japan) was performed routinely at the Public Health Laboratory; all the woman were negative. Commercial kits were used for rubella virus (Rubaset® EIA-G and EIA-M, Orion Diagnostica, Helsinki, Finland) and Toxoplasma gondii (T. gondii IgG and IgM EIA kit; Labsystems).
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Statistical methods |
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Results |
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The pregnancy rate was lowest in the upper SEA and highest in the intermediate SEA, 5.7 and 15.3% (Figure 1) (P = 0.001). The difference was evident in all age groups. In upper SEA there was only one (0.1%) pregnancy in a woman
19 years of age compared with 2.0% and 2.8% in the other SEA. More than 20% of pregnancies occurred in women
24 years of age in the lower SEA compared with 8.9% and 11.7% in same other age groups in the upper and intermediate SEA. The overall difference in age between the pregnant women in the three SEA was highly significant (P = 0.001).
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Neither parity nor number of gestations was associated with HCMV seropositivity. A three-point discrepancy between gestation and parity, indicative of 2 miscarriages, appeared in 114 of the 1088 women (in 8.8% of the seronegative, 11.2% of the IgG-positive and 13.6% of IgM-positive women). In the upper SEA the number of
2 miscarriages was 7.7%, and in the other SEA it was 11.2% and 11.4%. Thus, social environment seems to be the most powerful factor in predicting both IgG seroprevalence and recurrent HCMV infections, and with increasing age the seroprevalence remains at the same level, primary infections being few and distributed evenly among the different ages and SEA.
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Discussion |
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Chronic maternal infection is defined by the presence of HCMV-specific IgG antibodies without HCMV-specific IgM antibodies during the first 12 weeks of gestation. In our series, chronic infection was significantly higher among women in the lower SEA than in the other two groups, and showed no correlation with age, gestation or parity. The HCMV-specific IgM was also most frequent, 4.6%, in the lower SEA. Whether an IgM case is associated with primary infection or reactivation can be determined with an IgG avidity test, although the correlation is far from complete.1314 The presence of IgM-positive women with high or borderline avidity indicated that, compared with the other two groups, more than twice as many women in the lower SEA had apparent re-activations. Remarkably, the most frequent cause of reactivation of infection and intrauterine transmission of HCMV in immune women seems to be endogenous infection.25
In an earlier report, avidity <50% reflected an acute primary infection within 3 months, avidity >65% was always associated with an older infection,15,16 and only 20% of all IgM were associated with acute infections. This resembles our percentage of primary infections among IgM positive cases. Primary infections were distributed in every age group and in all the SEA. Clearly, the sensitivity of IgM in recurrences is low in HCMV infections, perhaps only 10%.6 Thus 90% of recurrences may remain unidentified.
A high proportion of seronegativity, and thus a high socioeconomic level, is regarded as a risk factor for severe congenital disease. However, families with a congenitally HCMV infected child have not been characterized. According to Stagno, if HCMV IgG seropositivity is 55%, congenital infections are transmitted half from primary and half from recurrent infections.26In the low income group, seropositivity is 82% and congenital infections are transmitted from primary infections in 25% and from recurrent infections in 75% of cases.
The children who are symptomatic at birth will be damaged. However, asymptomatic children may develop sequellae insidiously over time.27 Young, low socioeconomic group women excrete HCMV in 1128% of cases and in even greater numbers in late pregnancy. Excretion is rarer in early pregnancy but increases towards the end, 25%, or even >50%.28 Maternal antibodies afford substantial protection to the fetus but the protection is imperfect. According to a British study,10 most congenital symptomatic infections arise from recurrent maternal infections. Although this may be disputed and it contrasts with previous reports26 it, however, emphasizes the possible role of chronic infection.
The conclusion is often drawn that congenital HCMV would be more frequent and more severe in the upper socioeconomic groups, but this may not be true.10 Several reports indicate the importance of age and parity,24 which we were unable to confirm. Decisions about vaccination are not straightforward decisions.29 Pregnant women may not be protected from recurrences by vaccination and the seropositivity status is clearly associated with the socioeconomic status. The recurrence rate is much higher in the lower SEA with inherently high seropositivity. The same or some other CMV strain may be responsible for repeated infections.8 Notably, CMV seroprevalence in general seems to have been decreasing since 1980.30 Simple hygienic measures such as hand-washing may be the reason.8,31 This is consistent with the improvement in socioeconomic factors in accordance with our study.
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Acknowledgments |
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References |
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