Sentinel phenotype for rubella embryopathy: time-space distribution in Brazil.

The dyad comprising eye anomalies and congenital heart defects in the same newborn has been proposed as the best sentinel phenotype for the early detection of rubella embryopathy. Time-space birth prevalence distributions of the eye-heart dyad were described in 36 Brazilian hospitals from the Latin-American Collaborative Study of Congenital Anomalies - ECLAMC network, for the period 1994-2008. Seventy dyad cases observed among 554,531 births showed seasonal variation (Χ² = 5.84; p < 0.05), suggesting an environmental etiology, with an increase in cases in October-March and acrophase in December. The secular distribution of dyad prevalence rates was consistent with the distribution of rubella cases in Brazil, showing a decrease from 1994 to 2004, followed by an increase until 2008. Two geographic clusters were identified, one with high and the other with low dyad prevalence. In the high prevalence cluster, a secular increase was observed, starting in 1999, matching the rubella epidemic waves observed in Brazil in 1998-2000 and 2006.

Sentinel phenotype for rubella embryopathy: time-space distribution in Brazil / Fenótipo sentinela para embriopatia rubéolica: distribuição em tempo e espaço no Brasil

The dyad comprising eye anomalies and congenital heart defects in the same newborn has been proposed as the best sentinel phenotype for the early detection of rubella embryopathy. Time-space birth prevalence distributions of the eye-heart dyad were described in 36 Brazilian hospitals from the Latin-American Collaborative Study of Congenital Anomalies - ECLAMC network, for the period 1994-2008. Seventy dyad cases observed among 554,531 births showed seasonal variation (Χ2 = 5.84; p < 0.05), suggesting an environmental etiology, with an increase in cases in October-March and acrophase in December. The secular distribution of dyad prevalence rates was consistent with the distribution of rubella cases in Brazil, showing a decrease from 1994 to 2004, followed by an increase until 2008. Two geographic clusters were identified, one with high and the other with low dyad prevalence. In the high prevalence cluster, a secular increase was observed, starting in 1999, matching the rubella epidemic waves observed in Brazil in 1998-2000 and 2006.

A díade óculo-cardíaca havia sido proposta como o melhor fenótipo sentinela para detecção precoce da embriopatia rubéolica. Descrevem-se as distribuições têmporo-espaciais das prevalências ao nascimento dessa díade com material do Estudo Colaborativo Latino Americano de Malformações Congênitas (ECLAMC) em 36 hospitais brasileiros no período 1994-2008. Os 70 casos em 554.531 nascimentos mostraram uma variação sazonal significativa (Χ2 = 5,84; p < 0,05), o que sugere uma etiologia ambiental, com um aumento de casos de outubro a março com acrofase em dezembro. A variação secular das prevalências da díade foi compatível com o padrão observado para a distribuição da rubéola no país, com diminuição entre 1994-2004, e ulterior aumento até 2008. Identificaram-se dois conglomerados de alta e de baixa prevalência para a díade. Dentro do conglomerado de alta prevalência, observou-se significativo acréscimo secular a partir do ano 1999, não verificado no conglomerado de baixa prevalência, nem no resto dos hospitais em estudo, compatível com a série de surtos epidêmicos registrados para a infecção rubeólica no Brasil em 1998-2000 e em 2006.

Perinatal lessons from the past: Sir Norman Gregg, ChM, MC, of Sydney (1892-1966) and rubella embryopathy.

By identifying rubella infection in early pregnancy as a cause of congenital malformations and disabilities, Gregg alerted the medical profession to the importance of the prenatal environment.

Monitoring congenital rubella embryopathy.

BACKGROUND: Currently, all developed countries include rubella vaccination in their immunization programs, targeting the complete elimination of congenital rubella syndrome (CRS). In the underdeveloped world, where this severely disabling condition still exists, only a few countries have implemented vaccination policies, and almost no data on their effectiveness or on prevalence rates are available. The aims of the present work were to search for the best phenotype to be used as a sentinel for CRS in a large series of malformed newborns and to propose a CRS surveillance system, based only on clinical data. METHODS: A total of 43 infants diagnosed as having CRS were obtained from 19,184 multimalformed infants, ascertained by the Latin-American Collaborative Study of Congenital Malformations, World Health Organization (WHO) Collaborating Centre for the Prevention of Birth Defects (ECLAMC), over 3,883,165 consecutive births, between 1982 and 2003. They were distributed by country and the most frequent birth defects were identified. From the 19,184 multimalformed infants, all cases presenting the birth defects identified were selected. The sensitivity, specificity, and likelihood ratio (LR) in detecting CRS were determined for these birth defects, alone and in combination. The sample size of multimalformed infants required to detect different levels of increase in the rate of CRS was determined for three sentinel phenotypes. RESULTS: The rate of CRS was highest in Brazil. Based on the best possible combination of sensitivity, specificity, and LR, the dyad comprising eye anomalies and congenital heart defects was shown to be the most appropriate sentinel, with the lowest sample size required, to detect CRS in neonates. CONCLUSIONS: A surveillance system for CRS, based on clinical data in newborns, is being proposed, in an attempt to monitor ongoing vaccination policies, aimed at eliminating CRS in developing countries.

Secuelas oculares en recién nacidos son síndrome de TORCH / Ocular sequelae in newborns with TORCH syndrome

Se evaluó la incidencia de alteraciones oculares en infantes nacidos de madres con titulación positiva contra el complejo TORCH y la infección por sífilis. Incluimos a 33 pacientes, captados en el periodo de septiembre de 1997 a junio de 1998. Se valoró la presencia de alteraciones oculares congénitas en infantes con antecedentes de infección intrauterina por el síndrome de TORCH. Se incluyeron 8 mujeres (24.2 por ciento) y 25 hombres (75.7 por ciento). Las lesione que más se encontró fue: catarata en 6 pacientes (18.1 por ciento), coloboma en 2 pacientes (6.0 por ciento), microftalmía, entropión, queratoconjuntivitis, masa retrobulbar, desprendimiento de retina, coriorretinitis y atrofia óptica en los restantes pacientes (3.0 por ciento). Las infecciones intrauterinas influyen en el dessarrollo del ojo. Estos datos sugieren que el diagnóstico temprano de tales infecciones por el complejo TORCH permite realizar el tratamiento adecuado

Predictive value of serological tests in rubella virus infection during pregnancy.

In an attempt to define diagnostic criteria that may help to distinguish the congenital rubella syndrome (CRS) from subclinical intrauterine rubella virus (RV) infection, maternal and fetal serum samples were analyzed using (1) enzyme immunoassay employing RV synthetic peptides as antigen, (2) IgG avidity assay, and (3) immunoblot under nonreducing conditions, in addition to hemagglutination inhibition and commercial enzyme immunoassays. Infants born with CRS and their mothers were shown to reveal low or undetectable levels of E2-specific antibodies and deficient IgG recognizing the major neutralizing antibody-inducing epitope on the E1 protein (SP15). Antibody responses were normal in mothers with presumed RV reinfection as well as in asymptomatic infants born after maternal primary rubella. The results indicate that the maturation of specific humoral immune responses is obviously less efficient when intrauterine RV infection results in CRS. The detection of high avidity IgG, conformational E2-specific as well as SP15-reactive antibodies may serve as a potential predictor for a benign outcome of intrauterine RV infections.

Perinatal viral infections.

Among the TORCH agents, the occurrence of rubella and human T-lymphotropic virus type 1 (HTLV-1) in Japan were studied. Rubella epidemics occurred throughout Japan from 1964 to 1969 and from 1975 to 1979. Low prevalences of CRS were observed in northeastern Japan, and high prevalences in southwestern Japan, with the highest in Okinawa. These conditions could be explained by the lower rate of rubella H1 antibody in the female population of southwestern Japan. Time of maternal rubella was in the gestational age interval from 26 to 57 days for cataract, from 25 to 62 days for heart disease and from 16 to 131 days for deafness. HTLV-1 is the causative agent of adult T-cell leukemia. Main route of transmission of this virus is mother-to-child transmission, through breast milk. Among the 311 mother-child pairs in Okinawa, 65 mothers (20.9%) and 10 children (3.2%) were seropositive for HTLV-1. Ten (15.4%) of the 65 seropositive mothers had seropositive children. These children had acquired their HTLV-1 antibodies by the age of 3 years. A significant difference existed between the prevalence rate of HTLV-1 antibodies in mothers and children.