Early maternal Zika infection predicts severe neonatal neurological damage: results from the prospective Natural History of Zika Virus Infection in Gestation cohort study.

OBJECTIVE: To define the prevalence of adverse outcomes of maternal infection in a large cohort of ZIKV-infected Brazilian women and their infants. DESIGN: Prospective population-based cohort study. SETTING: Ribeirão Preto's region's private and public health facilities. POPULATION: Symptomatic ZIKV-infected mothers and their infants. METHODS: Prenatal/early neonatal data were obtained for all mother-child pairs. A subgroup of infants had cranial ultrasonography, eye fundoscopy, hearing and neurological examinations and Bayley III screening tests within 3 months of age. MAIN OUTCOME MEASURES: Prevalence of pregnancy losses and anomalies detected at birth or within 3 months according to the gestational age of infection. RESULTS: Overall, 511 ZIKV-infected women were identified from a total of 1116 symptomatic women; as there were two twins, there were a total of 513 fetuses included. Of these, 13 (2.5%; 95% CI 1.5-4.3) presented with major signs of congenital Zika syndrome (CZS). Of the 511 women, there were 489 livebirths and 24 (4.7%) pregnancy losses (20 miscarriages and four stillbirths). ZIKV-related anomalies occurred in the offspring of 42/511 (8.2%) mothers. Microcephaly or other CNS malformations were diagnosed in 1/4 (25.0%) stillbirths and in 19/489 (3.9%; 95% CI 2.5-5.9) of the liveborn infants. Fetal abnormalities were 14.0 (95% CI 7.6-26.0) times more likely with gestational infection occurring in ≤11 weeks. On follow up of 280 asymptomatic infants, 2/155 (1.3%) had eye abnormalities, 1/207 (0.5%) had CNS imaging findings and 16/199 (8%) presented neurological alert signs. CONCLUSIONS: This prospective population-based study represents the largest Brazilian cohort study of ZIKV in pregnancy. Congenital anomalies potentially associated with CZS are less frequent than previously thought. There is a strong association between the gestational age of infection (≤11 weeks) and a poorer early infant prognosis. A notable proportion of apparently asymptomatic newborns can present with subclinical findings within 3 months of age. TWEETABLE ABSTRACT: ZIKV and pregnancy: adverse outcomes are less common, more prevalent for first-trimester infections, and potentially subclinical.

Development of criteria for identifying neonatal near-miss cases: analysis of two WHO multicountry cross-sectional studies.

OBJECTIVE: To develop and test markers of neonatal severe morbidity for the identification of neonatal near-miss cases. DESIGN: This is a database analysis of two World Health Organization cross-sectional studies: the Global Survey on Maternal and Perinatal Health (WHOGS) and the Multicountry Survey on Maternal and Newborn Health (WHOMCS). SETTING: The WHOGS was performed in 373 health facilities in 24 countries (2004-2008). The WHOMCS was conducted in 359 health facilities in 29 countries (2010-2011). POPULATION: Data were collected from hospital records of all women admitted for delivery and their respective neonates. METHODS: Pragmatic markers (birthweight <1750 g, Apgar score at 5 minutes <7, and gestational age <33 weeks) were developed with WHOGS data and validated with WHOMCS data. The diagnostic accuracy of neonatal characteristics and management markers of severity was determined in the WHOMCS. RESULTS: This analysis included 290 610 liveborn neonates from WHOGS and 310 436 liveborn neonates from WHOMCS. The diagnostic accuracy of pragmatic and management markers of severity for identifying early neonatal deaths was very high: sensitivity, 92.8% (95% CI 91.8-93.7%); specificity, 92.7% (95% CI 92.6-92.8%); positive likelihood ratio, 12.7 (95% CI 12.5-12.9); negative likelihood ratio, 0.08 (95% CI 0.07-0.09); diagnostic odds ratio, 163.4 (95% CI 141.6-188.4). A positive association was found between the frequency of neonatal near-miss cases and Human Development Index. CONCLUSION: Newborn infants presenting selected markers of severity and surviving the first neonatal week could be considered as neonatal near-miss cases. This definition and criteria may be seen as a basis for future applications of the near-miss concept in neonatal health. These tools can be used to inform policy makers on how best to apply scarce resources for improving the quality of care and reducing neonatal mortality.

Early high CMV seroprevalence in pregnant women from a population with a high rate of congenital infection.

Congenital cytomegalovirus (CMV) infection rates increase with maternal seroprevalence due to transmission from maternal non-primary infection. CMV seroprevalence estimates of pregnant women are needed for planning strategies against congenital CMV transmission. We aimed to determine the age-specific prevalence of serum antibodies for CMV in a representative age-stratified sample of unselected pregnant women from a Brazilian population. A total of 985 pregnant women, aged 12­46 years (median 24 years), were enrolled. Overall CMV seroprevalence was 97% (95% confidence interval 95.8­98.0), with age-specific (years) prevalence as follows: 12­19 (96.3%), 20­24 (97.7%), 25­29 (97.1%), and 30­46 (96.7%). CMV seroprevalence is almost universal (97%) and is found at similar levels in pregnant women of ages ranging from 12 to 46 years. Because high CMV seroprevalence is found even in women of a younger age in this population, this finding suggests that the majority of primary CMV infections occur early, in infancy or childhood. As a consequence, vaccines currently under development to prevent primary infection may not be a solution for the prevention of congenital CMV infection in this population.

Incidence of congenital toxoplasmosis estimated by neonatal screening: relevance of diagnostic confirmation in asymptomatic newborn infants.

Congenital toxoplasmosis is rarely identified by routine clinical examination. The aim of this study was to estimate the incidence of the disease in the region of Ribeirão Preto, south-eastern Brazil. A definitive diagnosis was made on the basis of the persistence of anti-Toxoplasma IgG antibodies beyond 1 year of age. Blood samples obtained from 15,162 neonates and adsorbed onto filter paper were tested for anti-Toxoplasma IgM antibodies. Fifteen samples gave positive results. A definitive diagnosis was confirmed in five of the 13 infants (38.5%) who completed follow-up. These five infants presented with serum IgM and/or IgA antibodies, and clinical abnormalities. Disease incidence was estimated to be 3.3/10,000 (95% CI 1.0-7.7), indicating the need for preventive measures. Neonatal screening is feasible, but screening tests with a better performance are required; positive screening results must be carefully confirmed.

Factors associated with vertical HIV transmission during two different time periods: the impact of zidovudine use on clinical practice at a Brazilian reference centre.

Vertical HIV transmission rates and associated factors among mother-infant pairs cared for at a Brazilian reference centre from 1988 to 1993 (period 1), and from 1996 to 1999 (period 2) were evaluated. A total of 150 and 239 infants born to HIV+ mothers were enrolled at birth during these periods. No zidovudine prophylaxis was available in period 1. In period 2, 92.4% of the infants were exposed to zidovudine (54% started at delivery or in the post-natal period). During period 1, 25 of 129 infants were found to be infected (19.4%; 95% confidence interval [CI]=13-27) vs 20 of 232 (8.6%; 95% CI=5-13) during period 2 (P <0.01). After controlling for co-variables, this decline was due to zidovudine prophylaxis, either with complete (odds ratio [OR]=0.24; 95% CI=0.08-0.70) or incomplete (OR=0.37; 95% CI=0.17-0.81) regimens. Premature rupture of membranes (OR =3.2) and rhesus-negative blood type of the infant (OR=2.6) facilitated transmission. Although confirming the protective effect of zidovudine prophylaxis, alternative approaches aimed at pregnant women identified late are needed for this population.

Neonatal orbital abscess.

PURPOSE: To describe two cases of orbital abscess in neonates and to review the literature of orbital cellulitis in neonates. DESIGN: Two interventional case reports. METHODS: Photographs, orbital computed tomography scans, and full pediatric examination were obtained in two cases of orbital abscess in neonates. RESULTS: Acute ethmoiditis with orbital abscess formation was found in both infants. In one of them, Staphylococcus aureus was identified as the source of infection. CONCLUSIONS: The clinical findings of our cases concur with the literature (eight cases) indicating that orbital abscess caused by Staphylococcal ethmoiditis is the most common form of orbital cellulitis in neonates.

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

A rapid test for the diagnosis of congenital CMV infection is still needed. This study evaluated the usefulness of dried blood and urine samples collected on filter paper for detecting cytomegalovirus (CMV) by the polymerase chain reaction (PCR) assay compared with the use of liquid urine. Samples were obtained from 332 infants aged 1-7 days. Liquid urine samples were collected into bags, cultured in human fibroblasts, and processed using a multiplex PCR technique. Dried urine samples were obtained by placing a piece of filter paper in contact with the infant's genitals. The heels of neonates were punctured and capillary blood was blotted onto filter paper and dried. Dried blood and urine specimens were analyzed by multiplex PCR and nested-PCR assays. A diagnosis of congenital CMV infection was established by isolating the virus, and by detecting viral DNA in the liquid urine. Of the 332 liquid urine samples collected from 332 neonates, seven (2.1%) were positive for CMV and 325 were negative, by both cell culture and PCR assay. In dried samples, CMV DNA was detectable only with a nested PCR assay. Compared with known CMV infection status, 5/7 (71.4%) neonates were positive for congenital CMV infection using dried blood samples. All 325 uninfected neonates were negative. In the dried urine samples, 4/4 CMV-infected infants gave positive tests, and all 262 uninfected infants were negative. Although further improvements in sample collection and/or processing are still needed, PCR testing on dried urine or blood collected on filter paper is a promising approach in the diagnosis of neonatal CMV infection.

Predicting perinatal HIV infection in young Brazilian infants: How accurate are signs, symptoms and immunological abnormalities?

Early identification of infants perinatally infected with HIV (HIV+) requires costly laboratory tests which are not widely available in countries with limited resources. We evaluated the utility of detection of non-specific HIV-related signs and symptoms and immunological abnormalities in the diagnosis of perinatal HIV infection in Brazilian infants younger than 10 months of age and followed from birth. A total of 27 HIV+ and 43 uninfected infants were studied. All infants exhibited one or more non-specific HIV-related findings at least once. HIV+ infants were more frequently symptomatic than HIV- infants only when older than 3 months. Combinations of clinical and immunological findings resulted in high sensitivity (85-100%) and low specificity (25-65%) rates for the diagnosis of HIV infection. Conversely, low CD4+ cell counts and hyperimmunoglobulinaemia showed low sensitivity (52%) and high specificity (100%) rates. In conclusion, the detection of similar findings in HIV- and HIV+ infants underscores the need of early confirmatory laboratory testing.

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

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, 1,757 g) and 163 term infants (median gestational age, 39 weeks; median birth weight, 3,150 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.

[Neonatal nosocomial infections] / Infecções neonatais hospitalares.

OBJECTIVE: To review the current medical literature on neonatal nosocomial infections, emphasizing aspects of neonatal colonization, immune system and infection mechanisms, modes of transmission, epidemiology, surveillance and prevention of these infections, in addition to assessing peculiarities about etiologic agents and prophylactic recommendations. SOURCES: Electronic search in the Medline and LILACS databases, with selection of the most relevant articles published within the last ten years. SUMMARY OF THE FINDINGS: The several peculiarities that cause greater susceptibility to infection in newborns, and the survival of preterm infants due to the invasive procedures and treatment with broad spectrum antibiotics at intensive care units are responsible for prevalence rates of neonatal nosocomial infections between 9.3 and 25.6%. Neonatal nosocomial infections affect at least 50% of newborns who weigh less than 1500 g, which ends up increasing mortality rates. Full-term newborns frequently have skin and soft tissue lesions caused by gram-positive organisms. In neonatal intensive care units, sepsis and pneumonia are frequently diagnosed (especially those caused by S. aureus, S. epidermidis, E. coli, K. pneumoniae, and E. cloacae). An increasing frequency of resistance to several antimicrobial drugs has been observed. A nosocomial infection surveillance program tailored to the characteristics of the neonatal unit allows the identification of infection outbreaks, the rational use of antibiotics and the application of preventive measures. CONCLUSIONS: Neonatal nosocomial infections are a relevant problem. Their control can only be achieved if adequate measures concerning pregnant women, hospital environment, nursing staff, and newborns are adopted. Although new prophylactic measures are being proposed for preterm infants, they are costly and do not preclude continued epidemiological surveillance and control in neonatal units.

[Congenital and perinatal infections] / Infecções congênitas e perinatais.

OBJECTIVE: To review current information about congenital and perinatal infections, mainly related to their epidemiology in Brazil, mother-to-infant transmission, diagnosis, treatment and prevention. Particular aspects related to the agents T. pallidum, hepatitis B virus, human immunodeficiency virus, cytomegalovirus and T. gondii were considered. METHODS: The main published papers from the last 10 years were selected from a Medline database electronic search. RESULTS: Congenital or perinatal infections can occur in up to 10% of newborns. Although there are few Brazilian studies, available data suggest their relevance, mainly related to the occurrence of infection due to T. pallidum, HIV and CMV. At least 50% of the infected newborns are asymptomatic. However, because these infections may lead to long term sequelae, it is necessary to early identify infected pregnant women in order to implement specific preventive measures. Presently, laboratory methods for early diagnosis of fetal or neonatal infections are available. They are predominantly based on assays for detection of IgA or IgM specific antibodies and fragments of the microorganism nucleic acids by polymerase chain reaction. The available treatments had only limited success, because they often have failed to substantially modify the prognosis for infected infants. New treatments and outcome studies are needed. CONCLUSIONS: Congenital and perinatal infections are a relevant problem whose main current advances are related to prevention and laboratory diagnostic methods applicable to pregnant women, fetus or infants.

[Perinatal cytomegalovirus infection: commonly occurring but rarely diagnosed] / Infecção perinatal por citomegalovírus: muito freqüente mas pouco diagnosticada.

OBJECTIVE: To determine the incidence rate of perinatal cytomegalovirus (CMV) infection and to describe the clinical presentation of this infection in non-transfused term infants attended at a general hospital, in Ribeirão Preto, SP, Brazil. POPULATION AND METHODS: Thirty four infants free of CMV infection at birth were followed up during the first 4 months of life. Diagnosis of perinatal CMV infection was established by isolating the virus in tissue culture or by polymerase chain reaction DNA amplification (PCR) in urine samples. RESULTS: A 38.2% (13/34) incidence rate of perinatal CMV infection was detected, and only 3 of the infected infants were symptomatic (respiratory tract symptoms in one infant and splenomegaly in two). CONCLUSIONS: The results indicate a high incidence rate of perinatal CMV infection in the studied infants. Clinical symptoms were present in 23% of these patients, stimulating the investigation of this agent as a cause of pneumonitis and splenomegaly.

[Prevalence and clinical aspects of congenital cytomegalovirus infection] / Prevalência e aspectos clínicos da infecção congênita por citomegalovírus.

OBJECTIVES: The objectives of the present study were to determine the prevalence of congenital CMV infection, as well as to evaluate the importance of this agent as cause of congenital disease, and to describe the clinical manifestations in children attended at a General Hospital in Ribeirão Preto, SP, Brazil. POPULATION AND METHODS: A first group including 189 newborns and their mothers was evaluated for the prevalence of the congenital CMV infection. A second group including 130 newborns and 74 infants who presented clinical manifestations of congenital disease were also investigated to evaluate the importance of the CMV as a cause of this disease and to describe the clinical findings. Diagnosis of congenital CMV infection was established by detecting the virus using viral isolation in tissue culture, polymerase chain reaction DNA amplification in urine samples and detection of specific anti-CMV IgM and IgG by immunofluorescence indirect test. RESULTS: The prevalence of congenital CMV infection was 2.6% and the prevalence of CMV antibodies in mothers was 95%. In the first group, none of the 5 congenitally infected presented clinical apparent disease at birth, although one of them had intracranial calcifications. In the second group, CMV was recognized as a causative of congenital disease in 12 children (5.9%). Of these, 10(83%) were identified after the neonatal period. The clinical findings included hepatosplenomegaly (75%), jaundice with direct hyperbilirubinemia (42%), neurologic disease consisting of microcephaly and intracranial calcifications in 42% of these children. CONCLUSIONS: The prevalence of congenital CMV infection was similar to that reported in other studies about highly immune populations. Infants with asymptomatic congenital CMV infection may have diseases of the central nervous system that are not clinically evident at birth, such as punctate calcifications. CMV infected patients who are symptomatic at birth have a multisystem disease, and the differential diagnosis of any newborn with clinical abnormalities including involvement of the hepatobiliary, hematopoietic and central nervous systems should include congenital CMV infection. CMV was an important agent of these abnormalities, and the majority of symptomatic patients were identified after the neonatal period, making the diagnosis more difficult.

[Diagnosis of congenital and perinatal infection by cytomegalovirus using polymerase chain reaction]. / Diagnóstico de infecção congênita e perinatal por citomegalovírus utilizando a reação em cadeia da polimerase.

The practical application of a polymerase chain reaction (PCR) amplification for the diagnosis of congenital and perinatal cytomegalovirus (CMV) infections was evaluated. Three hundred five urine samples were tested by PCR and conventional virus isolation in cell culture. Viruria was detected in 47 urine samples by PCR using a primer pair which amplifies part of the major immediate-early (MIE) CMV genome. The PCR compared to virus isolation showed 89.6% sensitivity, 98.5% specificity and 91.5% positive predictive value. PCR with primer pairs amplifying parts of the glycoprotein B and glycoprotein H genes of CMV were used for confirmation of the positivity of the 47 urine samples. We concluded that this CMV PCR assay in urine has a suitable sensitivity for the diagnosis of congenital and perinatal infections and its specificity is highly increased by use of more than one pair of primers among the ones we used.

Congenital and perinatal cytomegalovirus infection in infants born to mothers infected with human immunodeficiency virus.

OBJECTIVES: To determine the rates of congenital and perinatal cytomegalovirus (CMV) infection among infants born to mothers infected with HIV compared with infants born to mothers not infected with HIV from a CMV-immune, low-income population. STUDY DESIGN: A total of 325 newborns from CMV-seropositive mothers were enrolled and evaluated for congenital CMV infection (150 infants from HIV+ mothers and 175 infants from HIV- mothers. A total of 101 infants from HIV+ mothers and 33 infants from HIV- mothers were evaluated for perinatal CMV infection. The virus was isolated from urine by culture in human fibroblasts and was detected by polymerase chain reaction at birth and at 15 days and 12 weeks of age. RESULTS: Only 13 of 150 HIV+ mothers (8.7%) had an AIDS-defining condition, and none had a late-stage HIV infection. Congenital CMV infection was detected in 4 of 150 (2.7%) infants from HIV+ mothers and in 5 of 175 (2.9%) infants from HIV- mothers (p = 1.00). Perinatal CMV infection was diagnosed in 8 of 101 (7.9%) infants from HIV+ mothers and in 13 of 33 (39.4%) infants from HIV- mothers (p < 0.00001). Most infants (93.9%) from HIV- mothers and only 5.9% of infants from HIV+ mothers were breastfed. CONCLUSIONS: CMV coinfection in mothers without advanced HIV disease from a CMV-immune population does not enhance the likelihood of congenital CMV infection. Perinatal CMV transmission from HIV-infected mothers may be decreased by avoiding breastfeeding. Further studies on mothers with late-stage HIV infection are needed.

Diagnóstico de infecção congênita e perinatal por citomegalovírus utilizando a reação em cadeia da polimerase / Diagnosis of congenital and perinatal infection by cytomegalovirus using polymerase chain reaction

Aplicou-se uma reação em cadeia da polimerase (PCR) no diagnóstico de infecção congênita e perinatal por citomegalovirus, comparando-a com a técnica de isolamento viral em cultura celular. Foram processadas 305 amostras de urina de crianças de 0 a 6 meses, por ambas as técnicas. Utilizou-se na PCR os primers que amplificam parte do gene codificador do principal antígeno precoce imediato de CMV. Detectou-se virúria em 47 amostras por PCR e comparando os resultados com aqueles obtidos pelo isolamento viral, observou-se copositividade de 89,6% e conegatividade de 98,5%. Estas amostras positivas tiveram o resultado confirmado por PCR utilizando outros primers que amplificam regiões dos genes codificadores das glicoproteínas B e H de CMV. O diagnóstico de infecção congênita e perinatal por CMV pela PCR mostrou sensibilidade comparável à do isolamento viral e o uso de vários primers conferiu alta especificidade ao teste.

The practical application of a polymerase chain reaction (PCR) amplification for the diagnosis of congenital and perinatal cytomegalovirus (CMV) infections was evaluated. Three hundred five urine samples were tested by PCR and conventional virus isolation in cell culture. Viruria was detected in 47 urine samples by PCR using a primer pair which amplifies part of the major immediate-early (MIE) CMV genome. The PCR compared to virus isolation showed 89.6% sensitivity, 98.5% specificity and 91.5% positive predictive value. PCR with primer pairs amplifying parts of the glycoprotein B and glycoprotein H genes of CMV were used for confirmation of the positivity of the 47 urine samples. We concluded that this CMV PCR assay in urine has a suitable sensitivity for the diagnosis of congenital and perinatal infections and its specificity is highly increased by use of more than one pair of primers among the ones we used.

[Congenital tuberculosis] / Tuberculose congênita.

OBJECTIVE: Considering the rarity and the significance of early diagnosis for planning appropriate treatment, a case of congenital tuberculosis is reported.CASE REPORT: After a prolonged stay in the Neonatal Intensive Care Unit (NICU) of a male pre-term infant without improvement, the diagnosis of tuberculosis was suspected when his mother underwent thoracotomy for valve replacement due to a subacute endocarditis. At this time, multiple pleural granulomas were detected and the diagnosis of tuberculosis was confirmed by histology. His mother seldom went to the NICU to see the baby and she was rarely very close to him in these occasions. After tuberculosis therapy, the baby gradually improved. CONCLUSION: Among the possible ways of transmission, the reported case was probably transmitted by aspiration of contaminated amniotic fluid in utero or at the time of delivery.

[Frequency of pregnant HBsAg carriers in a Brazilian community]. / Freqüência de gestantes portadoras do HBsAg em uma comunidade brasileira.

In view of the benefits of immunoprophylaxis among newborns of mothers who are seropositive for hepatitis B virus (HBV) surface antigen (HBsAG), these women must be correctly identified so that this measure can be instituted in Brazil. The research reported here studied 7992 women who gave birth in the Hospital das Clínicas of the Ribeirão Preto School of Medicine, University of São Paulo (HCFMRP-USP), Brazil, in order to determine the rate of serum reactivity of HBsAg and other markers of HBV infection among these women, and also to evaluate the risk factors for this infection. Serum reactivity for HBsAg was determined by means of an immunoenzymatic test (ELISA) carried out in two stages: the first with an incubation period of 2 hours (screening), and the second with an incubation period of 18 hours (confirmation) for those samples that were positive in the screening test. The markers anti-HBsAg, HBeAg, anti-HBcAg, and anti-HBeAG were tested in the samples that were confirmed positive. The screening test found 1.05% (95% CI: 0.84 - 1.30) of the samples to be positive for HBsAg. However, only 0.95% (95% CI: 0.75 - 1.19) were confirmed positive, the percentage being significantly higher among patients whose pregnancies had ended in abortion (1.84%) than among those who had given birth (0.84%) (X2, Yates correction = 7.76; P < 0.005). Risk factors for HBV infection could be identified for only 27.6% of the study subjects, based on their recall and reporting. Of the women with confirmed positive samples, 21.3% also were positive for HBeAG, indicating that these patients ran a greater risk of transmitting the virus vertically. These results underline the need for specific serologic studies in the final stage of pregnancy in order to offer the maximum benefit of neonatal immunoprophylaxis.

[Use of polimerase chain reaction for neonatal diagnosis of human immunodeficiency virus type 1 (HIV-1) perinatal infection]. / Uso da reação em cadeia da polimerase (PCR) para o diagnóstico neonatal de infecção perinatal pelo vírus da imunodeficiência humana tipo 1 (HIV).

The polymerase chain reaction (PCR) was evaluated for its ability to diagnose perinatal HIV-1 infection before the development of signs or symptoms of the disease in thirty-seven infants (median age of 5.5 days) born to HIV-1 infected women. Of 30 children with complete follow up (median of 25 months), 9 (30%) had serological and clinical features of HIV-1 infection and 21 (70%) were uninfected. Among the infected infants, 5/9 (56%) had positive neonatal PCR tests and 4/9 (44%) had negative PCR tests. None of the 21 uninfected children had positive PCR tests. The prognosis of HIV-1 disease in infected infants with a positive neonatal PCR positive test was similar to that of infected infants with a negative PCR test. In spite of not identifying all the infected infants, the PCR test is a useful tool for early diagnosis of HIV-1 perinatal infection, detecting infected newborns during gestation.

BCG vaccination of full-term infants with chronic intrauterine malnutrition: influence of immunization age on development of post-vaccination, delayed tuberculin hypersensitivity.

To determine the effect of intrauterine growth retardation (IUGR) on the response to BCG vaccination, we evaluated the specific delayed tuberculin hypersensitivity of 57 full-term infants with symmetric IUGR (SGA or small for gestational age) and 52 full-term infants with normal intrauterine growth (AGA or appropriate for gestational age). The infants were evaluated using post-vaccination skin tests to tuberculin purified protein derivative (PPD) and tuberculin lymphocyte transformation tests. Using a positive response to the skin test as an indicator of delayed hypersensitivity, we found that the rate of response to BCG in the SGA and AGA groups was similar. A total of 65% of infants with IUGR responded to BCG vaccination. The response rate among SGA infants who were vaccinated at 5 days of age, about 26 days of age (weight > or = 2500 g), 3 months of age, and 6 months of age was 68%, 47%, 69%, and 88%, respectively. The overall response rate for infants with no IUGR was 71%; the rate response to BCG vaccination among this group was 52% (those vaccinated at 5 days of age), 90% (3 months of age), and 80% (6 months of age). Our data suggest that the immunogenicity of BCG vaccine is similar in term infants who have normal or abnormal intrauterine growth and the presence of IUGR should not be a reason for delaying BCG vaccination.

PIP: In Brazil, pediatricians followed 109 infants born at the University Hospital of Ribeirao Preto in Sao Paulo every 2 weeks for 3 months and then at 6 months to examine the effect of intrauterine growth retardation (IUGR) on the response to BCG vaccination. They used a tuberculin purified protein derivative to determine tuberculin hypersensitivity and a lymphocyte transformation test to determine lymphocyte proliferation to tuberculin 12-14 weeks after vaccination. The rate of response to BCG in the IUGR infants was basically the same as that of infants whose weight was appropriate for gestational age (AGA) (65% vs. 71%). Specifically, the rate among IUGR infants vaccinated at 5 days old, once they weighed at least 2500 gm (around 26 days old), 3 months old, and 6 months old was 68%, 47%, 69%, and 88%, respectively. The rate among AGA infants vaccinated at 5 days old, 3 months old, and 6 months old was 52%, 90%, and 80%, respectively. The results indicated that BCG vaccination was more immunogenic as the infants aged than when they were newborns, regardless of intrauterine status. They demonstrated that waiting to administer the BCG vaccination when the IUGR infants weighed 2500 gm had no advantage over administering the vaccination when they were newborns. In developing countries with a high prevalence of tuberculosis, such a delay would place these especially vulnerable infants at greater risk of tuberculosis.