SUMMARY We reviewed studies that reported results of systematic cytomegalovirus (CMV) screening on fetuses and/or liveborn infants. The overall birth prevalence of congenital CMV infection was 0.64%, but varied considerably among different study populations. About 11% of live-born infants with congenital CMV infection were symptomatic, but the inter-study differences in definitions of symptomatic cases limit the interpretation of these data. Non-white race, low socioeconomic status (SES), premature birth, and neonatal intensive care unit admittance were risk factors for congenital CMV infection. Birth prevalence increased with maternal CMV seroprevalence. Maternal seroprevalence accounted for 29% of the variance in birth prevalence between study populations. Maternal seroprevalence and birth prevalence were both higher in study populations that were ascertained at birth rather than in the prenatal period. Thus, timing of ascertainment should be considered when interpreting birth prevalence estimates. Birth prevalence was inversely correlated with mean maternal age, but this relationship was not significant when controlling for maternal seroprevalence. The rate of transmission to infants born to mothers who had a primary infection or a recurrent infection during pregnancy was 32% and 1.4%, respectively. Possible maternal primary infections (i.e. seropositive mother with CMV IgM) resulted in congenital infections about 20% of the time, but are likely to represent a mixture of primary and recurrent infections. In summary, CMV is a common congenital infection worldwide that can lead to permanent disabilities. There is an urgent need for interventions that can reduce the substantial burden of this often overlooked disease. Copyright # 2007 John Wiley & Sons, Ltd.

Review and meta‐analysis of the epidemiology of congenital cytomegalovirus (CMV) infection

Cytomegalovirus establishes a lifelong latent infection following primary infection that can periodically reactivate with shedding of infectious virus. Primary infection, reactivation and reinfection during pregnancy can all lead to in utero transmission to the developing fetus. Congenital CMV infections are a major cause of permanent hearing loss and neurological impairment. In this literature review, we found that CMV infection was relatively common among women of reproductive age, with seroprevalence ranging from 45 to 100%. CMV seroprevalence tended to be highest in South America, Africa and Asia and lowest in Western Europe and United States. Within the United States, CMV seroprevalence showed substantial geographic variation as well, differing by as much as 30 percentage points between states, though differences might be explained by variation in the types of populations sampled. Worldwide, seroprevalence among non-whites tended to be 20-30 percentage points higher than that of whites (summary prevalence ratio (PR) = 1.59, 95% confidence interval (CI) = 1.57-1.61). Females generally had higher seroprevalences than males, although in most studies the differences were small (summary PR = 1.13, 95% CI = 1.11-1.14). Persons of lower socioeconomic status were more likely to be CMV seropositive (summary PR = 1.33, 95% CI = 1.32-1.35). Despite high seroprevalences in some populations, a substantial percentage of women of reproductive age are CMV seronegative and thus at risk of primary CMV infection during pregnancy. Future vaccine or educational campaigns to prevent primary infection in pregnant women may need to be tailored to suit the needs of different populations.

Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection.

This opinion describes the assessment of the risks to public health associated with bisphenol A (BPA) exposure. Exposure was assessed for various groups of the human population in three different ways: (1) external (by diet, drinking water, inhalation, and dermal contact to cosmetics and thermal paper); (2) internal exposure to total BPA (absorbed dose of BPA, sum of conjugated and unconjugated BPA); and (3) aggregated (from diet, dust, cosmetics and thermal paper), expressed as oral human equivalent dose (HED) referring to unconjugated BPA only. The estimated BPA dietary intake was highest in infants and toddlers (up to 0.875 µg/kg bw per day). Women of childbearing age had dietary exposures comparable to men of the same age (up to 0.388 µg/kg bw per day). The highest aggregated exposure of 1.449 µg/kg bw per day was estimated for adolescents. Biomonitoring data were in line with estimated internal exposure to total BPA from all sources. BPA toxicity was evaluated by a weight of evidence approach. “Likely” adverse effects in animals on kidney and mammary gland underwent benchmark dose (BMDL10) response modelling. A BMDL10 of 8 960 µg/kg bw per day was calculated for changes in the mean relative kidney weight in a two generation toxicity study in mice. No BMDL10 could be calculated for mammary gland effects. Using data on toxicokinetics, this BMDL10 was converted to an HED of 609 µg/kg bw per day. The CEF Panel applied a total uncertainty factor of 150 (for inter- and intra-species differences and uncertainty in mammary gland, reproductive, neurobehavioural, immune and metabolic system effects) to establish a temporary Tolerable Daily Intake (t-TDI) of 4 µg/kg bw per day. By comparing this t-TDI with the exposure estimates, the CEF Panel concluded that there is no health concern for any age group from dietary exposure and low health concern from aggregated exposure. The CEF Panel noted considerable uncertainty in the exposure estimates for non-dietary sources, whilst the uncertainty around dietary estimates was relatively low.

Scientific Opinion on the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs: Executive summary

Hospital-acquired neonatal infections in developing countries

Hepatitis B vaccines.

Objective Although an outstanding characteristic of the adrenocortical function of children and adults is its circadian rhythm, little information is available about the age of appearance of such rhythm in infancy. The main obstacle has been the ethical difficulty in obtaining serial blood samples from healthy infants. We monitored the development of cortisol daily rhythm using noninvasive salivary cortisol determination. Design and patients A longitudinal study of a group of 9 healthy infants was performed. Salivary samples were obtained in the morning, afternoon and night at 2, 4, 8, 12, 16, 20 and 24 post-natal weeks from all infants. Measurements Cortisol was determined by RIA in 25-microl salivary samples. Two techniques based on assay coefficients of variation were employed to characterize a normal circadian pattern of cortisol. Results Five infants (55%) established and maintained their cortisol rhythm as early as at 2, 4 and 8 weeks of age. In the remaining 4 infants the age of appearance was 12 and 20 weeks. This rhythm emerged in the group as a whole at a mean age of 8 weeks. Conclusions Our data suggest that, in most normal infants, the development of hypothalamic-pituitary-adrenal axis circadian maturation may occur at a much earlier age than previously described.

Longitudinal evaluation of the development of salivary cortisol circadian rhythm in infancy

Summary
OBJECTIVE The circadian rhythm of cortisol is established at between 8 and 12 postnatal weeks in term infants. However, there is limited information about the effect of prematurity on this rhythm. We evaluated the emergence of the salivary cortisol circadian rhythm in premature infants and its relationship to the onset of sleep daily rhythm.

DESIGN AND PATIENTS A longitudinal study of a group of nine premature infants (gestational age 31–34 weeks) was performed. Salivary samples were obtained in the morning and at night at 2, 4, 8, 12, 16, 20 and 24 postnatal weeks and the babies' sleeping periods were recorded by their mothers.

MEASUREMENTS Cortisol was determined by RIA in 25–μl salivary samples. Two techniques based on assay coefficients of variation were used to characterize the circadian pattern of cortisol.

RESULTS Five infants (55%) established and maintained their cortisol rhythm at 2 and 8 postnatal weeks. In the remaining four infants the age of appearance was 12 and 16 weeks. This rhythm emerged in the group as a whole between 8 and 12 postnatal weeks. The circadian rhythm of sleep was detected starting from the eighth postnatal week.

CONCLUSIONS Our data suggest that in this group of premature infants the circadian maturation of the hypothalamic-pituitary-adrenal axis occurred at the same postnatal age as reported for term infants and that there was a parallelism between the appearance of such rhythm and the onset of sleep rhythm.

The emergence of salivary cortisol circadian rhythm and its relationship to sleep activity in preterm infants.

Background, Cytomegalovirus (CMV) is the most frequent cause of congenital infections in humans. Prematurity occurs in as many as 34% of infants with symptomatic congenital CMV infection. Objective. To determine the clinical presentation and frequency of congenital CMV infection among preterm infants and full-term infants from a population with a high seroprevalence rate. Design/methods. A total of 289 preterm infants (median gestational age, 34 weeks; median birth weight, 1757 g) and 163 term infants (median gestational age, 39 weeks; median birth weight, 3150 g) sequentially born were included in the study. Serum IgG antibodies to CMV were measured in all mothers. One urine sample was collected within the first 7 days of age from all newborns. Virus isolation in urine samples was performed by tissue culture, and viral DNA was detected by a multiplex PCR. CMV infection was diagnosed in infants with virus excretion detected by both methods on at least two occasions within the first 3 weeks of life. Results. Maternal CMV seropositivity rate was 95.7%. Congenital CMV infection was detected in 6 of 289 (2.1%) (95% confidence interval, 0.84 to 4.68) preterm infants and in 3 of 163 term infants (1.8%) (95% confidence interval, 0.48 to 5.74) (P > 0.05). Four of 6 preterm infants with congenital CMV infection were symptomatic, but none of the term infants was symptomatic (P = 0.16). Conclusion. The frequency of congenital CMV infection in preterm newborn infants from mothers with a high seropositive rate was similar to that found in term infants. No significant difference was found between the proportion of symptomatic infants among preterm and term infants. Our finding of symptomatic congenital CMV infection underscores the need of further evaluation of correlates of congenital symptomatic infection in highly immune populations.

Salim Moysés Jorge

Papers

Longitudinal evaluation of the development of salivary cortisol circadian rhythm in infancy

The emergence of salivary cortisol circadian rhythm and its relationship to sleep activity in preterm infants.

Congenital cytomegalovirus infection in preterm and full-term newborn infants from a population with a high seroprevalence rate.

Correlation between plasma and salivary cortisol levels in preterm infants

Usefulness of blood and urine samples collected on filter paper in detecting cytomegalovirus by the polymerase chain reaction technique.