Risk Factors for Congenital Cytomegalovirus Infection in the Offspring of Young Women: Exposure to Young Children and Recent Onset of Sexual Activity

METHODS

RESULTS

Study population characteristics are shown in Table 1. Both case patients and control subjects are predominantly single, black women. The source of prenatal care was similar for both case patients and control subjects: ∼95% received prenatal care from the county health department. More than two thirds of the case patients and control subjects enrolled in prenatal care in the first trimester of their pregnancy. The case patients were significantly less likely to have a previous pregnancy and also were younger at delivery than the control subjects. Household size was slightly larger for the case patients than for the control subjects. However, the number of children who were younger than 6 years and residing in the household was similar for both the case patients (median: 0; range: 0–4 children) and the control subjects (median: 1; range: 0–5 children). Only 3 (2.0%) of the case patients and 7 (1.9%) of the control subjects reported ever having been employed as a child care or nursery worker.

The percentage of case patients who provided direct care for children who were younger than 6 years was greater than the control subjects for all age groups (Fig 1). Direct care is defined as changing diapers, bathing, and feeding a child in either the woman's family or a friend's in the year before her delivery. The case patients were significantly more likely to provide care for infants who were younger than 12 months (OR: 1.9; 95% CI: 1.3–2.9) and for children who were 13 to 35 months of age (OR: 2.1; 95% CI: 1.4–3.3) than the control subjects. However, the case patients and control subjects did not differ in caring for children who were aged 36 to 59 months in the year before their deliveries (OR: 1.2; 95% CI: 0.8–1.9). Even after stratifying by parity, direct care of young children remained associated with an increased risk for delivering an infant with congenital CMV infection in both primiparous (OR: 3.3; 95% CI: 1.7–6.9) and multiparous (OR: 2.2; 95% CI: 1.2–4.3) women.

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FIGURE 1

Comparison of the proportion of case mothers with control subjects who cared directly for preschool children in the 12 months before delivery according to age groups (months).

Of the women who provided care for preschool children, the frequency of care did not differ between the case patients and control subjects; most women cared for children weekly. Among the case patients, 70.6% cared for children once or more a week, 21.1% once or more a month, and 8.3% only several times a year. Among the control subjects for the same categories, the percentages were 73.6%, 18.4%, and 8%, respectively. Also, children who were cared for in the year before delivery did not differ between the case patients (mean ± SD: 2.5 ± 2) and control subjects (mean ± SD: 2.4 ± 1.9).

Table 2 includes potential risk factors that were associated with delivering an infant with congenital CMV infection. Maternal age <25 years at delivery and being primiparous both were associated with delivering an infant with congenital CMV infection. Having 3 or more people living in the household during the year before delivery slightly increased the risk for delivering a child with congenital CMV infection, although this factor was of borderline significance. Direct care of both children who were younger than 3 years and children who were younger than 6 years was associated with an increased risk for congenital CMV infection, although having children who were younger than 6 years residing in the household was not associated with an increased risk for congenital CMV infection. Recent onset of sexual activity (<2 years) was associated with an increased risk for delivering an infant with congenital CMV infection, although sexual debut at an early age (<16) and the number of lifetime sexual partners (>3) did not increase the risk for delivering an infant with congenital CMV infection. Control subjects were more likely to have a history of sexually transmitted infections than the case patients. Case patients reported higher percentages of gonorrhea, chlamydia, genital warts, syphilis, and trichomoniasis during pregnancy than the control subjects, but these differences were not statistically significant. However, when sexually transmitted infections during pregnancy were combined, women with any sexually transmitted infection (gonorrhea, chlamydia, genital warts, syphilis, genital herpes, or trichomoniasis) during pregnancy had an increased risk for delivering an infant with congenital CMV infection compared with women who had no identified sexually transmitted infections. Bacterial vaginosis during pregnancy also was associated with delivery of an infant with congenital CMV infection but was of borderline significance.

For evaluation of the contribution of recent sexual activity and young children as CMV sources for maternal and congenital CMV infections, a variable that combined both onset of sexual activity <2 years before delivery and caring for young children in the year before delivery was created. As seen in Fig 2, more case patients were observed to have these combined exposures than the control mothers. Women who delivered infants with congenital CMV infection were 6.5 times (OR: 6.5; 95% CI: 3.1–13.4) more likely to have both factors compared with women with neither factor. Women with only exposures to young children (OR: 3.0; 95% CI: 1.7–5.2) and without recent onset of sexual activity also were more likely to have a child with congenital CMV infection than women who had neither exposure. Likewise, women whose sexual debut was <2 years before delivery (OR: 3.4; 95% CI: 1.2–8.9) but who did not care for children during the year before their delivery were more likely to deliver a child with congenital CMV infection than were women who neither cared for children nor became sexually active recently.

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FIGURE 2

Distribution of 2 factors (caring for children who were younger than 6 years in the year before delivery and recent onset of sexual activity <2 years before delivery) in the case patients and control subjects.

Maternal age, race, parity, number in household, recent onset of sexual activity, history of STDs, sexually transmitted infections during pregnancy, and direct care of young children were entered into a logistic regression model. After adjustment for other factors, providing direct care of preschool children, recent onset of sexual activity, sexually transmitted infections during pregnancy, household size, and maternal age all were independently associated with delivering a newborn with congenital CMV infection. A woman's providing direct care of a child who was younger than 6 years in the year before her delivery significantly increased the risk for congenital CMV infection in her offspring, as indicated by the adjusted OR (aOR) of 2.9 (95% CI: 1.8–4.7). Women whose sexual debut occurred within 2 years of delivery (aOR: 2.5; 95% CI: 1.4–4.5) or reported sexually transmitted infections during pregnancy (aOR: 1.6; 95% CI: 1.1–2.5) also had an increased risk for delivering an infant with congenital CMV infection. Also, living in the household with >3 people in the year before delivery (aOR: 2.0; 95% CI: 1.1–3.9) and maternal age <25 years at delivery (aOR: 2.8; 95% CI: 1.4–5.7) both were associated with delivering an infant with congenital CMV infection. Neither history of sexually transmitted infections nor parity was independently associated with delivering a newborn with congenital CMV infection. After adjustment for race, maternal age, parity, and sexually transmitted infections during pregnancy, women who cared for young children and had recent onset of sexual activity had the greatest risk for delivering an infant with congenital CMV infection compared with women without either exposure (aOR: 7.2; 95% CI: 3.2–16.1).

DISCUSSION

Our results indicate that young children and sexual transmission both contribute to congenital CMV infections in this young urban population. Providing direct care of young children in the year before delivery seems to be an important source of maternal CMV infections and increases the risk for delivering a newborn with congenital CMV infection in this population. The recent onset of sexual activity and the presence of sexually transmitted infections during pregnancy indicate that young women in the population are acquiring CMV infections through sexual exposures to CMV, which in turn can lead to in utero CMV infections. Women who both care for young children and have recent onset of sexual activity have the greatest risk for delivering an infant with congenital CMV infection (OR: 7.2). Maternal age <25 years at delivery and living in a household with 3 or more people in the year before delivery also contribute to congenital CMV infections in this population.

More than 76% of the case mothers cared for young children either in their household or in a friend's household. It is interesting that because case patients are more likely to be primiparous, their exposures to CMV by young children are occurring not as they care for their own children but when they care for a relative's or a friend's child. Previous studies have shown that children who excrete CMV may spread infection to a parent and to other adults in the household.^4,5,8 Other studies have demonstrated that having children in child care centers with high rates of CMV infection correlates with an increased risk for CMV infection in the parents of these children.^2,4,7 Possibly young children in these households were acquiring CMV infection in child care centers, resulting in CMV exposure for other household members. However, in both the case patients and control subjects, fewer than one third of the young children who resided in the homes were in any type of group child care, suggesting that child care centers are not an important source of CMV infection for mothers in this urban population. Also, possible occupational exposure to CMV while working in a child care facility or nursery did not account for the observed increased risk for congenital CMV infection, because only 3 case patients (2.0%) and 7 (1.9%) control subjects listed any employment as child care or nursery workers.^24–26

Recent onset of sexual activity (<2 years) in young women increased the risk for congenital CMV infection in their offspring. This finding suggests that recent sexual exposure to CMV resulted in maternal CMV infections that may have occurred in the months or year before conception and also during pregnancy. Previous work suggested that the risk for congenital CMV infection remains elevated even when primary maternal infection occurs months before conception.²⁷

Although individual sexually transmitted infections were not independently associated with delivering infants with congenital CMV infection, the case patients had higher percentages of gonorrhea, chlamydia, genital warts, syphilis, and trichomoniasis than the control patients. The association with sexually transmitted infections during pregnancy may be only an indicator of recent sexual activity and recently acquired CMV infections. However, a study of women who attended an STD clinic found that CMV was isolated from the cervix 6.5 times more often when other sexually transmitted infections were present.¹³ It is possible that other sexually transmitted infections during pregnancy may enhance the transmission of CMV from mother to fetus. A prospective study that captures the temporal relationship between CMV infection²⁸ and other sexually transmitted infections is needed to clarify the role of concomitant infections on in utero transmission of CMV.

Earlier sexual debut (<16 years of age), multiple sexual partners (>3), and history of sexually transmitted infections were not associated with increases in congenital CMV infection in our population. However, early sexual debut, multiple sexual partners, and history of sexually transmitted infections have been reported to be associated with CMV seropositivity in other populations.^14,15,29 These factors may be indicative of earlier CMV exposures, resulting in women's becoming CMV seropositive before pregnancy and therefore decreasing their risk for delivering newborns with congenital CMV infection. We previously reported that maternal immunity to CMV years before pregnancy is protective for offspring in future pregnancies.³⁰

Young maternal age as a risk factor for congenital CMV infection has been observed in previous reports.^19,30,31 This study also found that women aged 25 years or less at delivery were more likely to have an infant with congenital CMV infection than women who were older. Young maternal age may be a marker of recent exposure to CMV, although it also may be indicative of a biological effect of age on maternal infection. Possibly the combination of an age-related factor with recent exposure to the virus in young women enhances CMV infection during pregnancy and increases the risk for transmission to the fetus.¹⁹

Another risk factor for congenital CMV infection that was identified in our study was residing in a household with 3 or more people. This risk factor was independent of young children's living in the household. Our study did not collect information on the number of rooms in the house, so we were not able to assess crowding or other living conditions that may have contributed to CMV infections and subsequent transmission to the fetus. However, the case patients (69%) were more likely to live in households where their parents or grandparents were the heads of household compared with the control mothers (54%). In many of these parental households, other siblings and their children also were living in the house, resulting in larger households and more opportunities for exposures to CMV among the case mothers.

This study may have underestimated the number of individual sexually transmitted infections in the population because the study relied primarily on maternal recall to document the presence of infections during pregnancy. Underestimation may be attributable to a lack of understanding by the participant or an unwillingness of the participant to reveal previous sexually transmitted infections. We attempted to minimize the possible underestimation of exposures by interviewing the women without other family members present, using a standardized questionnaire, and carefully reviewing the prenatal records for laboratory culture and identification dates of sexually transmitted infections during pregnancy. The combination of using both the questionnaire and the prenatal summaries allowed us to capture most reported and documented sexually transmitted infections. Overall, in both the case patients and control subjects, the estimates of sexually transmitted infections are similar to previous reports of STDs in young women within the population.^18,32

To minimize further the possibility of differential maternal recall between the case patients and control subjects, we used similar interview methods and collection of prenatal summaries for both groups. Besides using a standard interview, the interval between delivery and interview was the same for both case patients and control subjects. Also, because >95% of the case patients and control subjects received their prenatal care within the same system, it is unlikely that collection of exposure information differed between the groups.

Our study findings describe maternal CMV exposures that result in congenital CMV infections in a predominantly unmarried, low-income, black delivery population. Although these young women's CMV exposure opportunities may have been more frequent, there is no evidence to suggest that if women in other populations are caring for young children or have recently become sexually active, then they would not have a similar risk for congenital CMV infection in their offspring. It is likely that predominantly married, middle to upper income, white delivery populations also are being exposed to CMV while caring for young children.

For prevention of congenital CMV infection, young women of childbearing age should be informed about CMV transmission routes.³³ Young women who are considering pregnancy or who are already pregnant should be instructed to practice good hygiene (ie, hand-washing) when caring for young children.³⁴ Adolescents and young women should be advised to avoid salivary and genital contact with others. However, changing behavior through health communication is challenging. A randomized, clinical trial that provided information on CMV and the importance of hand-washing failed to show a decrease in CMV acquisition by women of childbearing age, demonstrating the difficulty in changing behaviors,³⁵ yet successes have been observed in lowering the risk for HIV infection in black adolescents through health education interventions.^36–38 Even if behavioral changes through health communication decreases some congenital CMV infections, more likely an effective vaccine that is given to children or young teens and could prevent congenital infection would be more successful in preventing congenital CMV infection in most populations.