Vertical transmission of hepatitis C virus in a cohort of 2,447 HIV-seronegative pregnant women: a 24-month prospective study.

BACKGROUND: Mother to infant transmission of hepatitis C virus (HCV) has been extensively studied in mothers with human immunodeficiency virus (HIV) infection, whereas fewer data are available on the vertical HCV transmission in HIV-negative women. METHODS: Between January 1995 and June 1997, 78 consecutive HCV-positive/HIV-negative women with their offspring entered this prospective study aimed to define the prevalence of and risk factors for HCV vertical transmission. Risk factors for HCV were carefully sought, and HCV viral load and genotype were determined in all positive mothers. The infants were tested for alanine aminotransferase (ALT) and HCV-RNA at birth and at 4, 8, 12, 18, and 24 months of age. RESULTS: Eight of 60 (13.3%) infants born to HCV-RNA positive mothers acquired HCV infection, but only 2 (3,3%) were still infected by the end of follow-up. Infants' genotypes matched that of the mothers. ALT levels were in the normal range in all study subjects throughout the follow-up. High maternal viral load (P < 0.05), possession of HCV risk factors (P < 0.004), and history of blood transfusion (P < 0.05) were associated with increased risk of HCV vertical transmission. CONCLUSIONS: This long-term prospective study shows that, although vertical transmission from HIV-negative mothers occurs in 13% of cases, there is a high rate of spontaneous viral clearance (75%). High maternal viral load and mothers belonging to HCV risk categories were the only variables predictive of the vertical transmission.     

Prospective study of mother-to-infant transmission of hepatitis C virus

BACKGROUND: Mother-to-infant transmission of hepatitis C virus (HCV) could become the main route of HCV infection in the future because there are no methods available to prevent vertical infection. The aim of this study was to determine the incidence of mother-to-infant transmission in infants born to mothers who tested positive for anti-HCV antibodies and to elucidate associated risk factors for transmission. METHODS: Screening was conducted for 16,800 pregnant women with an anti-HCV antibodies test, and 154 mothers were positive. From the positive group 141 mothers were enrolled in the study and their 147 infants were followed from birth for serum alanine aminotransferase activity, anti-HCV antibodies and HCV RNA. HIV infection was tested in 73 of 141 mothers, all of whom were negative. RESULTS: Thirty-three infants were dropped from the study because they were followed for <6 months or were not tested adequately. Of the 114 infants finally evaluated 9 (7.8%) had detectable HCV RNA. The transmission rate was not influenced by the mode of delivery [vaginal delivery, 8 of 90 vs. cesarean section, 1 of 24 (P = 0.396)] or by the type of feeding [9 of 98 for breast-fed infants vs. 0 of 16 for formula-fed infants (P = 0.243)]. All infected infants were born to mothers who had HCV viremia at the delivery (P = 0.040) and to those with a high viral load (P = 0.019). CONCLUSIONS: Our prospective study showed that the transmission rate of mother-to-infant HCV infection was 7.8% in anti-HCV antibody-positive mothers. Risk was related to the presence of maternal HCV viremia at delivery and a high viral load in the mothers.     

Mother-to-Infant transmission of hepatitis C virus (HCV) in Brazil

Sixty-one women with anti-HCV antibodies, detected by a third-generation enzyme immunoassay (EIA3), were prospectively recruited for investigation of vertical HCV transmission during child-birth, at the University Hospital of the Catholic University of Campinas, Brazil, between January 1994 and July 1998. Six of the women presented coinfection with the human immunodeficiency virus type 1 (HIV-1). All of the 72 children born in this period were followed at least until they were 18 months of age. Analyses of anti-HCV, HCV RNA, and alanine aminotransferase were performed in a minimum of two blood samples during follow-up. One (2.4 per cent; 95 per cent CI, 2.2-7) of the 42 children born to HCV viremic mothers was both anti-HCV and HCV RNA-positive, with altered ALT levels. Passively transferred maternal anti-HCV antibodies became undetectable within 9-12 months. None of the nine infants born to HIV-1 infected mothers were infected either by HIV or HCV. Thus, the mother-infant HCV transmission rate is low and seems to be associated with maternal HCV RNA positivity.     

Breastfeeding and hepatitis C virus (HCV): the need for a careful appraisal]

We review the available data on the possible role of breast-feeding in hepatitis C virus (HCV) transmission to infants of HCV-RNA-positive mothers. Current knowledge about HCV excretion through breast milk, HCV infection of breast-fed infants by mothers contaminated after delivery, and vertical transmission risk to infants breast-fed by chronic HCV viremic mothers are presented. Vertical transmission risk by breast-feeding HCV-RNA-positive mothers is unclear: no study has been performed with the aim and the required methodology to evaluate HCV transmission risk related to breast-feeding duration. Recommendations to HCV-RNA-positive mothers who wish to breast-feed their infant are discussed in light of present knowledge about HCV secretion in breast milk, mother-to-infant HCV transmission, and historical records on vertical transmission of other viruses to infants breast-fed by their viremic mothers.     

Transmission of hepatitis C virus from infected mother to offspring during subsequent pregnancies

BACKGROUND: Several studies have demonstrated that hepatitis C virus (HCV) may be transmitted from mother to offspring. To date, however, little is known about the risk of vertical transmission during subsequent pregnancies. The purpose of this study was to evaluate the risk of vertical HCV transmission in offspring in subsequent pregnancies of HCV infected women. METHODS: In a multicenter study, two groups of index cases were selected. Group 1 included 75 children investigated for HCV infection during prospective studies of vertical transmission. Group 2 included children born to HCV-infected mothers and found to be HCV infected, independent of studies on vertical transmission. All children in the index cases had one or more siblings. Anti-HCV, HCV-RNA (determined by polymerase chain reaction), and HCV genotype were evaluated in all the infected children, their mothers, and siblings. RESULTS: The results indicate that a mother who has already delivered an HCV-infected baby is not at greater risk of infecting her second child. Duration of maternal infection does not seem to be a risk factor in offspring infection, because HCV infection is equally distributed among first-born infants and infants of subsequent births. Because clustering of HCV infection among siblings appeared to be rare in this study, data also indirectly confirm that the risk of horizontal transmission of HCV among siblings is low. CONCLUSION: For practical purposes, the current observations indicate that mothers who have already delivered an HCV-infected child can be advised that this event does not increase the probability of infecting the second child.     

Follow-up of transmission of hepatitis C to babies of human immunodeficiency virus-negative women: the role of breast-feeding in transmission

BACKGROUND: The studies on hepatitis C virus (HCV) vertical transmission, the effect of potential risk factors and the role of breast-feeding have reported conflicting results. PATIENTS AND METHODS: Seventy-three infants of 63 anti-HCV-positive and anti-HIV-negative mothers were studied from 1993 to 1999 in the south of Spain. The mean period of follow-up in children was 29.2 +/- 19 months (range, 8 to 76 months); 6 (8%) children were lost to follow-up. Breast milk was studied for HCV-RNA in 68 samples of 35 mothers. RESULTS: Alanine aminotransferase was high in 19 (26%) and HCV-RNA was positive in 46 (63%) pregnant woman. Breast milk HCV-RNA was negative in nonviremic mothers and positive in 20% of the viremic mothers. The overall rate of vertical HCV transmission was 11.9% (n = 8) (95% confidence interval, 6 to 23%) if HCV-RNA was positive one or more times, but only 1.5% (n = 1) (95% confidence interval, 0.1 to 9%) if HCV-RNA was permanently positive. Seven HCV-infected children did not develop antibodies to HCV, and they had a spontaneous clearance of the virus. A 10-month-old baby was HCV-RNA-positive from birth to the end of the follow-up. The genotype in each of the infants was consistent with that of their mother. The rate of HCV transmission was higher for infants of mothers with higher HCV viremia (P < 0.01) and also for infants whose mothers were HCV-RNA-positive in breast milk (P < 0.05). There were no statistically significant differences between other risk factors. CONCLUSION: The presence of transitory viremia without seroconversion indicates that the vertical transmission of HCV is not important. This could be related to the viral charge and ingestion of milk of HCV-RNA-positive mothers. However, to advise avoidance of maternal breast feeding, it would be necessary to conduct larger studies.     

感染丙型肝炎病毒的孕妇及其新生儿随访观察

目的了解丙型肝炎病毒(HCV)母婴垂直传播情况及HCV感染后对新生儿体格发育的影响。方法用ELISA法对1023名孕妇静脉血做抗HCV检测,阳性者对其新生儿脐带血做抗HCV检测。阳性者(包括产妇及其新生儿)进一步做HCVRNA检测;对抗HCV阳性新生儿做10～12个月随访,观察HCV感染指标及新生儿喂养、患病、生长发育情况。结果产妇HCV感染率为2.74％(28/1023);抗HCV阳性产妇中HCVRNA检出率为75％(21/28);抗HCV阳性产妇的新生儿脐血中抗HCV检出率为46.43％(13/28),其中检出HCVRNA阳性5例。对抗HCV阳性新生儿1年随访,抗HCV阴转率为69.23％(9/13),实验组新生儿母乳喂养率57％明显低于对照组85％,实验组儿童人均患病1.25次,而对照组儿童为0.5次,有非常显著性差异,身长、体重指标明显落后于对照组。结论母婴间存在着HCV的垂直传播;HCVRNA的存在不但增加了母婴垂直传播的比率,而且延缓了抗HCV的阴转;HCV的感染非常明显地影响了新生儿的体格发育。     

An epidemiological survey of hepatitis C virus infection in Italian children in the decade 1990-1999.

BACKGROUND: A retrospective-prospective survey of Italian children with hepatitis C virus (HCV) infection was planned in 1998 to explore the epidemiologic features of infection during the past decade. METHODS: Anti-HCV-positive patients (or HCV RNA-positive infants) aged 1 month to 16 years, consecutively observed in 20 pediatric Institutions, were considered. An anonymous epidemiologic questionnaire based on clinical records was used. RESULTS: From 1990 through March 1999, 606 patients were observed (296 boys, average age 5.8 years). Maternal infection (46% of cases) and blood transfusions (34%) were the most frequent risk factors. Of 279 infected mothers, 61% did not recall a putative source of infection (by history, many could possibly have had exposure through routes such as therapeutic injections with nondisposable material), whereas 94 (34%) admitted drug abuse, including 49 (17%) coinfected with human immunodeficiency virus (HIV). Only 157 (26%) children were born after 1991: 90% of their mothers were infected (11% were HIV coinfected vs. 25% mothers of older children, P < 0.01). CONCLUSIONS: Maternal infection is a prominent source of pediatric HCV infection in Italy. The fact that most mothers had a history of covert exposure to HCV, probably through percutaneous routes that are no longer operating, and that the number of those with HIV coinfection has decreased suggests that the frequency of pediatric infection could decrease in the future.     

Vertical and horizontal transmission of Candida albicans in very low birth weight infants using DNA fingerprinting techniques

BACKGROUND: Very low birth weight infants (VLBW, < or = 1500 g) are at increased risk for invasive disease caused by fungi, and colonization is an important risk factor. This study was designed to examine the effect of maternal flora on Candida colonization of VLBW infants. METHODS: Body site samples were collected within 24 hours of delivery from mothers who gave birth to VLBW infants, from their infants at birth, and then weekly for 12 weeks or until death or discharge. Yeast isolates were identified as Candida albicans by standard methods and typed by DNA fingerprinting using a C. albicans strain-specific DNA probe (CARE-2). RESULTS: Sixty-six percent (50/76) of mothers were colonized with yeast and 51% (39/76) of their infants had a Candida species isolated at least once. Of 46 infants born to C. albicans-colonized mothers, 18 (39%) became colonized with C. albicans. Twenty-two percent (17/76) of the infants in the study were colonized with C. albicans by 1 week of age; 76% of these infants (13/17) were born to C. albicans-colonized mothers suggesting vertical transmission. DNA fingerprinting was performed on these 13 mother-infant pairs and 11 pairs demonstrated identical band patterns, confirming vertical transmission. However, of all infants colonized with C. albicans by the first week of age, just 65% (11/17) had a maternal source, and among all infants colonized at any time point, only 41% (11/27) became colonized by vertical transmission. CONCLUSIONS: Both vertical and horizontal transmission contribute to Candida colonization of VLBW infants in the neonatal intensive care unit.     

Prevalence of hepatitis C virus (HCV) infection and its vertical transmission in Egyptian pregnant women and their newborns

We studied the prevalence of hepatitis C virus (HCV) antibody seropositivity using ELISA (Ortho Diagnostic system, 3rd generation test) polymerase chain reaction testing of HCV-RNA (PCR, Promega) and serum alanine transferase (ALT) level in 100 healthy, HIV-negative, pregnant women who delivered spontaneously at the Alexandria University Hospital, and their newborns. Some risk factors were studied using Fisher's exact test. Nineteen per cent of pregnant women were HCV seropositive and 14 of them (14/19) had circulating HCV-RNA, detected by PCR. Nine of the babies born to the 19 HCV seropositive females had circulating antibodies, whereas HCV-RNA was detected in five of them. This gives a vertical transmission risk of 5/14 (36 per cent) for mothers carrying the HCV-RNA and 5/19 (26 per cent) for those having circulating HCV antibodies. History of previous blood transfusion, elevated serum ALT level, and history of infection with schistosomiasis were significant risk factors for HCV infection in mothers. In addition to the previous factors, maternal history of jaundice, stillbirth and hepatomegaly were significant risk factors for neonatal infection. The occurrence of early jaundice and the presence of congenital anomalies in the newborns were non-significant risk factors. In conclusion, our data indicate a high prevalence of HCV seropositivity in Egyptian HIV-negative pregnant women with a significant high rate of vertical transmission of HCV.     

Growth in the first 5 years of life is unaffected in children with perinatally-acquired hepatitis C infection

OBJECTIVES: To identify the effect of vertical hepatitis C virus (HCV) infection or exposure on growth in childhood. STUDY DESIGN: Children (n=1203) born to HCV-infected mothers were followed up from birth prospectively in centers of the European Paediatric Hepatitis C virus Network. Z-scores compared height- and weight-for-age in HCV-infected and -uninfected children, adjusting for other factors using linear regression. We also quantified the effect of maternal chronic infection with HCV on childhood growth. RESULTS: There was no significant effect of vertical HCV infection on growth (height P=.223, weight P=.095) nor a significant effect of maternal chronic infection with HCV (height P=.733, weight P=.274). Prematurity and maternal injecting drug use were associated with a significant reduction in height (P < .001) and weight (P < .001) in all HCV-exposed children. CONCLUSIONS: This population of HCV exposed infants has higher rates of maternal injecting drug use and prematurity than standard populations and so there are implications for growth of these children, but this is not a direct result of HCV infection or exposure to chronic maternal HCV infection.     

Maternal HIV Infection and Vertical Transmission of Pathogenic Bacteria

BACKGROUND: HIV-exposed newborns may be at higher risk of sepsis because of immune system aberrations, impaired maternal antibody transfer and altered exposure to pathogenic bacteria. METHODS: We performed a secondary analysis of a study (clinicaltrials.gov, number NCT00136370) conducted between April 2004 and October 2007 in South Africa. We used propensity score matching to evaluate the association between maternal HIV infection and (1) vaginal colonization with bacterial pathogens; (2) vertical transmission of pathogens to the newborn; and (3) sepsis within 3 days of birth (EOS) or between 4-28 days of life (LOS). RESULTS: Colonization with group B Streptococcus (17% vs 23%, P = .0002), Escherichia coli (47% vs 45%, P = .374), and Klebsiella pneumoniae (7% vs 10%, P = .008) differed modestly between HIV-infected and uninfected women, as did vertical transmission rates. Maternal HIV infection was not associated with increased risk of neonatal EOS or LOS, although culture-confirmed EOS was >3 times higher among HIV-exposed infants (P = .05). When compared with HIV-unexposed, neonates, HIV-exposed, uninfected neonates (HEU) had a lower risk of EOS (20.6 vs 33.7 per 1000 births; P = .046) and similar rate of LOS (5.8 vs 4.1; P = .563). HIV-infected newborns had a higher risk than HEU of EOS (134 vs 21.5; P < .0001) and LOS (26.8 vs 5.6; P = .042). CONCLUSIONS: Maternal HIV infection was not associated with increased risk of maternal bacterial colonization, vertical transmission, EOS, or LOS. HIV-infected neonates, however, were at increased risk of EOS and LOS.     

Prevalence of hepatitis C virus infection in urban children

OBJECTIVES: To determine the prevalence of hepatitis C virus (HCV) infection in children with an unknown or negative human immunodeficiency virus (HIV) status attending an urban hospital pediatric primary care clinic, and to identify HCV risk factors in their mothers. STUDY DESIGN: This was a cross-sectional study of 1034 children tested for HCV antibodies (anti-HCV) after excluding children known to be HIV-positive. We assessed maternal HCV risk factors through structured interviews with a sample of mothers (n=573) and through review of available medical records (n=347) for a subsample of mother-child pairs. Means, proportions, and 95% confidence intervals were used to estimate the prevalence of anti-HCV and maternal risk factors. RESULTS: One child (0.1%; 95% CI, 0.002, 0.5) was anti-HCV positive. History of blood transfusion was reported by 7% of mothers and intravenous drug use (IVDU) by 1.8%. A subsample of mothers significantly underreported IVDU when compared with medical record review (1.5% vs 7.8%, P<.001). CONCLUSIONS: Our findings suggest that universal screening of children for HCV in high-risk urban communities is not warranted. However, self-report may not be reliable for identifying mothers with a history of IVDU, for whom HCV testing is recommended.     

Preventing mother-to-child transmission of HIV-1

Over the last 10 years, interventions to reduce the transmission of HIV-1 from mother to child have been extremely successful in the UK in pregnant women aware of their HIV status. Judicious use of pre-labour caesarean section, formula feeding and antiretroviral therapy has reduced transmission to less than 1% in these mothers and their infants. Before the introduction of such interventions, natural history data showed vertical transmission rates of around 25%. The risk of transmission from mother to child has been associated with advanced maternal HIV disease, maternal plasma HIV viral load and CD4 lymphocyte count, mode of delivery, duration of rupture of membranes, prematurity and breast-feeding. Attention is now turning to the minimisation of possible drug side effects in both mother and infant, as women are increasingly conceiving on combination antiretroviral therapy. The reduction of mother-to-child transmission of HIV following current UK guidelines is discussed.     

Sudden infant death syndrome in infants born to HIV-infected and opiate-using mothers.

OBJECTIVE: This study was undertaken to determine the role of opiate use during pregnancy as a predisposing factor for sudden infant death syndrome (SIDS) in infants born to HIV-infected mothers. METHODS: In order to identify all infant deaths and their cause and association with maternal opiate use, the data of a nationwide prospective cohort study of HIV-infected mothers and their children were extracted and analysed for a 13-year period. RESULTS: 24 (5.1%) infant deaths were observed out of 466 infants followed up until death or at least 12 months of life. 3 (0.6%) of them were due to non-accidental trauma and were not associated with maternal opiate use. 7 (1.5%) died due to SIDS, which was confirmed by autopsy. All SIDS cases occurred in infants born to mothers reporting use of opiates during pregnancy (n = 124). The relative risk of SIDS compared to the general population was 18 (95% CI 9 to 38) for all infants of HIV-infected mothers, and 69 (95% CI 33 to 141) for those with intrauterine opiate exposure (p<0.001). CONCLUSIONS: Compared to the Swiss general population, the risk for SIDS in this cohort of infants born to HIV-infected mothers was greatly increased, but only for mothers reporting opiate use during pregnancy. This effect appeared not to be mediated by prematurity, low birth weight, perinatal HIV infection or antiretroviral drug exposure.     

Interferon-gamma and interleukin-10 production among HIV-1-infected and uninfected infants of HIV-1-infected mothers

Immunologic consequences of exposure to HIV-1 in utero are still poorly understood. This study investigates relationships between type-1 [interferon-gamma (IFN-gamma)] and type-2 (IL-10) cytokine production and maternal-infant HIV-1 transmission. Cord blood leukocytes from deliveries of 71 HIV-1-infected and 11 uninfected mothers were tested for in vitro IFN-gamma and IL-10 production after phytohemagglutinin (PHA) stimulation. The infants of these HIV-1-infected mothers were followed prospectively after birth to determine HIV vertical transmission, and IFN-gamma and IL-10 production was measured again at 6 mo. Median PHA-stimulated IFN-gamma production was 210 pg/mL in cord blood cells from infected and 73 pg/mL from uninfected mothers (p = 0.12), and median PHA-stimulated IL-10 production was 491 pg/mL in cord blood cells from infected and 161 pg/mL from uninfected mothers (p = 0.004). PHA-stimulated IFN-gamma and IL-10 production alone were not significantly associated with transmission, but relationships between the two cytokines differed among infected and uninfected infants of HIV-1-infected mothers. PHA-stimulated IFN-gamma and IL-10 production was positively correlated among infected (r = 0.7, p = 0.12 in cord blood and r = 0.66, p = 0.03 at 6 mo) but not uninfected infants, and stronger relative production of IFN-gamma to IL-10 was observed among exposed uninfected than among infected infants (p = 0.04). Exposure in utero to HIV-1 may augment production of IL-10 detectable in fetal cord blood. Stronger relative production of IFN-gamma to IL-10 in cord blood cells from infants of HIV-1-infected mothers may be associated with protection against perinatal HIV infection.     

Association between low birth weight and infant mortality in children born to human immunodeficiency virus 1-infected mothers in Tanzania

BACKGROUND: The relationship between low birth weight and infant mortality among children born to human immunodeficiency virus (HIV)-infected mothers has not been thoroughly investigated. METHODS: A total of 1078 HIV-infected pregnant women in Tanzania were followed up until delivery and with their infants thereafter. The babies' HIV status was assessed at birth, 6 weeks and every 3 months thereafter. Using Cox proportional hazards models, we estimated the associations of low birth weight with neonatal, post-neonatal and infant mortality and further examined whether the association between low birth weight and mortality was modified by pediatric HIV infection. RESULTS: Among 823 singletons, low birth weight was strongly related to neonatal mortality (relative risk, 5.14; 95% confidence interval, 2.32-11.39). The association with postneonatal mortality was modified by child's HIV status. Among infants who were either negative or indeterminate at 6 weeks of age, low birth weight was associated with a 3-fold increased risk of mortality (relative risk, 3.16; 95% confidence interval, 1.36-7.37). In the positive infants, however, the association was no longer significant. CONCLUSIONS: Although the importance of preventing HIV transmission cannot be overemphasized, efforts to reduce the incidence of low birth weight would enhance the benefit of preventing HIV transmission. Even in populations with no access to antiretroviral treatments, interventions to reduce the incidence of low birth weight would result in a significant reduction in infant mortality.     

Retrospective study of risk factors of vertical transmission of hepatitis C virus

IntroductionDespite the low prevalence of paediatric HCV infection and its initial mild clinical expressiveness, chronic infection could progress into cirrhosis and/or hepatocarcinoma. It is essential to control vertical transmission. Recent studies show that up to 50% of transmissions occur within the uterus.Material y methodsA retrospective study was conducted on 17 cases of (Hepatitis C virus) HCV infection registered over a period of 8 years. Vertical transmission risk factors were analysed, in order to introduce primary prevention.ResultsOnly parenteral drug addiction significantly increased the rate of HCV transmission; HIV co-infection was not a confounding factor. HCV viremia, HIV co-infection, liver dysfunction and/or duration of the infection did not appear to affect the rate of transmission. Caesarean section, amniocentesis and internal monitoring may be risk factors (not statistically significant), but not prolonged vaginal delivery after amniotic membrane rupture. Breastfeeding showed protection.ConclusionsThe effect of viremia on the risk of transmission is not clearly established, despite the importance usually attributed. Lack of viremia does not discount the risk of transmission, due to viral RNA detection can be intermittent, so it should be interpreted cautiously. Immunosuppression secondary to HIV co-infection implies a higher risk of transmission, but this effect decreases by improving immune competence by antiretroviral treatment. With regard to the birth characteristics, time after the rupture of membranes has not shown being a risk factor; being the caesarean not advisable as a good alternative to finish the pregnancy. Breastfeeding does not increase the risk, even it can be protective. This results would be justified by the low viral content of milk, its inactivation by gastric pH and its immunological benefits.Given that retrospective studies results are limited, prospective studies need to be carried out in order to improve the understanding of the role of possible risk factors and to provide a clear preventive guidelines. At the moment it is essential to control all the children born of mothers with HCV infection.     

A prospective study of infants of human immunodeficiency virus seropositive and seronegative women with a history of intravenous drug use or of intravenous drug-using sex partners, in the Bronx, New York City

A prospective study was conducted in the Bronx, New York, of 70 infants of human immunodeficiency virus (HIV)-infected (n = 33) and uninfected (n = 37) mothers who had a history of intravenous drug use or of intravenous drug-using sex partners. Infants were observed from birth to a median age of 23 months (range 3 to 54 months). HIV infection was confirmed in seven infants (21%) of seropositive mothers; six developed HIV disease, with symptoms observed in the first year. Of these, three died (3, 9, and 36 months) of HIV-related causes; 3 of 4 survivors were greater than 25 months of age. HIV symptoms preceded or were concurrent with abnormalities in T-lymphocyte subsets; postneonatal polymerase chain reaction confirmed HIV infection in five infants with symptoms and one without symptoms. Among infants of seropositive mothers, seven without laboratory evidence of HIV (including polymerase chain reaction) had findings suggestive of HIV infection, including persistent generalized lymphadenopathy, hepatosplenomegaly, oral candidiasis, parotitis, and inverted T-lymphocyte ratios. These findings were not observed in infants of seronegative mothers. Although the presence of HIV proviral sequences was associated with HIV disease, the observation of indeterminate symptoms in at-risk infants indicates the importance of long-term clinical follow-up to exclude HIV infection. Disease manifestations in comparable infants of seronegative mothers are important for assessment of the impact of maternal drug use, development of specific clinical criteria for early diagnosis of HIV and eligibility for antiretroviral therapy.     

When does mother to child transmission of hepatitis C virus occur?

OBJECTIVE: To investigate when hepatitis C virus (HCV) infection from mother to child occurs, and evaluate possible associated factors. DESIGN: Prospective cohort study. PATIENTS: Fifty four HCV infected children tested within three days of birth and their mothers. MAIN OUTCOME MEASURES: HCV RNA polymerase chain reaction (PCR) results. RESULTS: Seventeen of the children (31%, 95% confidence interval 19% to 46%) were positive in the first 3 days of life and could be assumed to have acquired infection in utero. Testing PCR positive was not associated with sex (53% v 49% boys; p=0.77) or mode of delivery (29% elective caesarean section in both groups; p=0.98). Children with evidence of intrauterine infection were significantly more likely to be of lower birth weight and infected with genotype 1 (58% v 12%, p=0.01). Although a higher proportion of infants born to HCV/HIV co-infected women were PCR positive in the first 3 days of life, this difference did not reach statistical significance; excluding infants born to co-infected women did not affect the results. Thirty seven of the children (68%) were negative in the first 3 days of life, 27 of whom were positive when tested again at 3 months, and nine were first PCR positive after 3 months (one child had no further tests). CONCLUSIONS: These results suggest that at least one third and up to a half of infected children acquired infection in utero. Although postpartum transmission cannot be excluded, these data suggest that it is rare. The role of HCV genotypes in the timing and mechanism of infection should be explored further.