Risk Of Postnatal Transmission Research Articles

SARS-CoV-2 perinatal transmission and neonatal outcomes across four different waves of COVID-19 pandemic: A nationwide prospective cohort study from the Italian Society of Neonatology

ObjectivesTo describe how SARS-CoV-2 infection at the time of delivery affected maternal and neonatal outcomes across four major waves of the COVID-19 pandemic in Italy. MethodsThis is a large, prospective, nationwide cohort study collecting maternal and neonatal data in case of maternal peripartum SARS-CoV-2 infection between February 2020 and March 2022. Data were stratified across the four observed pandemic waves. ResultsAmong 5201 COVID-19-positive mothers, the risk of being symptomatic at delivery was significantly higher in the first and third waves (20.8-20.8%) than in the second and fourth (13.2-12.2%). Among their 5284 neonates, the risk of prematurity (gestational age <37 weeks) was significantly higher in the first and third waves (15.6-12.5%). The risk of intrauterine transmission was always very low, while the risk of postnatal transmission during rooming-in was higher and peaked at 4.5% during the fourth wave. A total of 80% of positive neonates were asymptomatic. ConclusionThe risk of adverse maternal and neonatal outcomes was significantly higher during the first and third waves, dominated by unsequenced variants and the Delta variant, respectively. Postnatal transmission accounted for most neonatal infections and was more frequent during the Omicron period. However, the paucity of symptoms in infected neonates should lead us not to separate the dyad.

Management and short-term outcomes of neonates born to mothers with active perinatal SARS-CoV-2 infection

ObjectiveWe report here on the management and outcomes of neonates born to mothers with active perinatal SARS-CoV-2 infection.Study designIn this prospective study, eligible neonates were enrolled in a database to track in-hospital outcomes and followed up outpatient periodically till 2 months of age to assess for late onset symptoms of infection.ResultsFrom April 2020 to February 2021, 67 mothers with perinatal SARS-CoV-2 infection and 70 at-risk neonates were included. Two neonates (3%) tested positive for SARS-CoV-2 within 48 h of life but remained asymptomatic during hospitalization and at all follow-up periods. Three infants were reported to have a febrile illness in 2 months follow up period, none of which was attributable to SARS-CoV-2.ConclusionOur data supports the emerging evidence which describes a probable low risk of vertical transmission of SARS-CoV-2. We also demonstrate a low risk of post-natal transmission or late-onset symptomatic infection with SARS-CoV-2.

Perioperative Implications of Obstetric Anaesthesia Care during COVID-19 Crisis

This article reviews the WHO and CDC guidelines related to obstetrics keeping in view the current Covid-19 pandemic. We are currently facing an unprecedented healthcare crisis caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is spread by human-to-human transmission through droplet and direct contact, causing mild symptoms in the majority of cases, but critical illness, bilateral viral pneumonia, and acute respiratory distress syndrome (ARDS) in a minority. We suggest how personal protective equipment’s (PPE’s) and specific infection control policies related to the risk of viral transmission to the anaesthetists, intensivists and other healthcare workers can be minimised particularly in obstetric patients. Although pregnancy doesn’t appear to exhibit higher susceptibility to COVID-19 than the general population but implementing strict infection control in the maternity department presents unique challenges. Particularly it necessitates decreasing the risk of postnatal transmission from mother to neonate and methods to accommodate emergency patients to labour ward and emergency care with a high patient turnover. Performing routine and emergency procedures for obstetric patients, such as neuraxial anaesthesia, is made more technically difficult and time consuming by wearing a PPE. These new challenges have anaesthetic implications and mandate a change in approach for team working, protocols for perioperative anaesthesia care and infection prevention policies. With limited evidence as of now but antenatal vertical transmission appears to be rare.Placental samples, amniotic fluid, cord blood, neonatal throat swabs and breast milk samples from COVID-19 infected mothers have all tested negative in various case series. There is currently no evidence concerning transmission through genital fluids. Pregnant patients presenting to the emergency room and labour ward should be risk stratified and then screened for covid-19 irrespective of being symptomatic or not before admission and subsequent care provided taking all the precautions. Aerosol generation during labour, particularly when coupled with symptoms secondary to COVID-19 lung sequelae, may increase airborne transmission. For these reasons, surgical facemasks should be worn by the parturient Proper donning and doffing of PPE is paramount for decreasing the risk of transmission of infection for labour epidural, OT’s and obstetric ICU’s and needs creation of space within the older system and newer guidelines and protocols to be implemented in letter and spirit.

Evaluation of Rooming-in Practice for Neonates Born to Mothers With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Italy

The management of mother-infant dyads during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic constitutes a major issue for neonatologists. In mothers with SARS-CoV-2 infection, current recommendations suggest either to separate the dyad or encourage protected rooming-in under appropriate precautions. No data are available regarding the risk of mother-to-infant transmission of SARS-CoV-2 during rooming-in. To evaluate the risk of postnatal transmission of SARS-CoV-2 from infected mothers to their neonates following rooming-in and breastfeeding. A prospective, multicenter study enrolling mother-infant dyads from March 19 to May 2, 2020, followed up for 20 days of life (range, 18-22 days), was performed. The study was conducted at 6 coronavirus disease 2019 maternity centers in Lombardy, Northern Italy. Participants included 62 neonates born to 61 mothers with SARS-CoV-2 infection who were eligible for rooming-in practice based on the clinical condition of the mother and infants whose results of nasopharyngeal swabs were negative at birth. Mothers with SARS-CoV-2 infection were encouraged to practice rooming-in and breastfeeding under a standardized protocol to minimize the risk of viral transmission. Clinical characteristics and real-time reverse transcriptase-polymerase chain reaction for SARS-CoV-2 on neonatal nasopharyngeal swabs at 0, 7, and 20 days of life. Of the 62 neonates enrolled (25 boys), born to 61 mothers (median age, 32 years; interquartile range, 28-36 years), only 1 infant (1.6%; 95% CI, 0%-8.7%) was diagnosed as having SARS-CoV-2 infection at postbirth checks. In that case, rooming-in was interrupted on day 5 of life because of severe worsening of the mother's clinical condition. The neonate became positive for the virus on day 7 of life and developed transient mild dyspnea. Ninety-five percent of the neonates enrolled were breastfed. The findings of this cohort study provide evidence-based information on the management of mother-infant dyads in case of SARS-CoV-2 maternal infection suggesting that rooming-in and breastfeeding can be practiced in women who are able to care for their infants.

Women living with HIV in high‐income settings and breastfeeding

Guidelines in high-income settings recommend breastfeeding avoidance amongst women living with HIV (WLWH). Increasingly, WLWH in high-income settings, who are well-treated with fully suppressed viral loads, are choosing to breastfeed their infants, even with these recommendations. The purpose of this article is to review existing research and guidance on infant feeding amongst WLWH in high-income countries and to identify gaps in this evidence that require further investigation. Current evidence on the risk of HIV transmission through breastfeeding in the context of antiretroviral therapy (ART), the significance of cell-associated virus, transmission risk factors, retention in care and adherence postpartum, infant prophylaxis and antiretroviral exposure, and monitoring of the breastfeeding WLWH are summarized. A latent HIV reservoir is persistently present in breast milk, even in the context of ART. Thus, suppressive maternal ART significantly reduces, but does not eliminate, the risk of postnatal transmission of HIV. There are currently limited data to guide the optimal frequency of virologic monitoring and the clinical actions to take in case of maternal detectable viral load whilst breastfeeding. Moreover, retention in care and adherence to ART in the postpartum period may be difficult and more research is needed to understand what clinical and psychosocial support would benefit these mothers so that successful engagement in care can be achieved. The long-term effects of antiretroviral drug exposure in the infants also need further exploration. Thus, there is a need for collecting enhanced surveillance data on WLWH who breastfeed and their infants to augment clinical guidance in high-income settings.

Maternal Humoral Immune Responses Do Not Predict Postnatal HIV-1 Transmission Risk in Antiretroviral-Treated Mothers from the IMPAACT PROMISE Study.

To design immune interventions that can synergize with antiretroviral therapy (ART) to reduce the rate of HIV mother-to-child transmission (MTCT), it is essential to characterize maternal immune responses in the setting of ART during pregnancy and breastfeeding and define their effect on MTCT. Prior studies reported an association between breast milk envelope (Env)-specific antibodies and antibody-dependent cell cytotoxicity (ADCC) activity with reduced postnatal transmission. In this study, we investigated whether these immune correlates were similarly associated with protection in a matched case-control study of mother-infant pairs receiving maternal ART or infant nevirapine prophylaxis during breastfeeding in the International Maternal-Pediatric-Adolescent AIDS Clinical Trials Network Promoting Maternal-Infant Survival Everywhere (PROMISE) trial, assessing postnatal transmission risk in 19 transmitting and 57 nontransmitting mothers using conditional logistic regression models adjusted for maternal plasma viral load. The odds ratios of postnatal MTCT for a 1-unit increase in an immune correlate were 3.61 (95% confidence interval [CI], 0.56, 23.14) for breast milk Env-specific secretory IgA (sIgA), 2.32 (95% CI, 0.43, 12.56) for breast milk and 2.16 (95% CI, 0.51, 9.14) for plasma Env-specific IgA, and 4.57 (95% CI, 0.68, 30.48) for breast milk and 0.96 (95% CI, 0.25, 3.67) for plasma ADCC activity, with all CIs spanning 1.0. Interestingly, although mucosal IgA responses are poor in untreated HIV-infected women, there was a strong correlation between the magnitudes of breast milk and plasma Env-specific IgA in this cohort. In this analysis of the small number of postnatal virus transmissions in the landmark PROMISE study, no single antibody response was associated with breast milk transmission risk.IMPORTANCE Each year, >150,000 infants become newly infected with HIV-1 through MTCT despite ART, with up to 42% of infections occurring during breastfeeding. Several factors contribute to continued pediatric infections, including ART nonadherence, the emergence of drug-resistant HIV strains, acute infection during breastfeeding, and poor access to ART in resource-limited areas. A better understanding of the maternal humoral immune responses that provide protection against postnatal transmission in the setting of ART is critical to guide the design of maternal vaccine strategies to further eliminate postnatal HIV transmission. In this study, we found that in women treated with antiretrovirals during pregnancy, there was a positive correlation between plasma viral load and breast milk and plasma IgA responses; however, conclusions regarding odds of MTCT risk were limited by the small sample size. These findings will inform future studies to investigate maternal immune interventions that can synergize with ART to eliminate MTCT during breastfeeding.

Higher likelihood of 6-months exclusive breastfeeding among HIV infected than uninfected mothers: a household survey in Kenya

BackgroundExclusive breastfeeding (EBF) (breast milk feeding without additional food or drink, except medicine) is associated with deceased risk of postnatal transmission of HIV from mother to child.MethodsThis analysis used data from a household survey in Western Kenya in 2011. Participants were mothers with HIV and uninfected mothers, aged ≥14 years who gave birth in the prior year (ever breastfed) within the Kenya Medical Research Institute/US Centers for Disease Control and Prevention (KEMRI/CDC) Health and Demographic Surveillance System. Data on breastfeeding counseling and knowledge and practices regarding breastfeeding were collected. Rates and correlates of EBF were determined using multivariable logistic regression.ResultsOf 652 mothers enrolled in the study, 435 were included in this analysis. Median age was 28 years among 154 mothers with HIV and 25 years among 281 uninfected mothers. Mothers with HIV were more likely than uninfected mothers to report breastfeeding counseling at a health facility (88.9% vs. 51.6%, respectively, p < 0.001) and EBF for 6-months (64.9% versus 34.5%, p < 0.001). Premastication (pre-chewing of food by adults prior to feeding to children) was less prevalent among mothers with HIV (3.9% vs. 13.2% p = 0.001) who were also more knowledgeable about potential risk of HIV transmission through premastication (83.1% vs 71.2% p = 0.005). Mothers with HIV who EBF for six months were 3.68-fold more likely to report counseling on EBF (aOR 3.68; 95% CI: 1.00,13.70). Uninfected mothers with polygamous marriage, any antenatal care visit, unskilled delivery and delayed breastfeeding initiation (> 1 h) were less likely to practice EBF for six months 62% (aOR 0.38; 95%CI: 0.20,0.94), 72% (aOR 0.28; 95%CI: 0.10,1.00), 54% (aOR 0.46; 95% CI: 0.22,1.00) and 46% (aOR 0.54; 95%CI: 0.30,1.00) respectively.ConclusionsMothers with HIV were more likely to report breastfeeding counseling at a health facility, EBF for six months and less likely to practice premastication than uninfected mothers. Lessons learned from breastfeeding counseling in mothers with HIV could be used to improve awareness and change breastfeeding practices for all mothers.

Human milk oligosaccharide concentration and risk of postnatal transmission of HIV through breastfeeding

The inefficiency of HIV breast-milk transmission may be caused by the presence of immunologically active factors, including human milk oligosaccharides (HMOs). We investigated whether HMO concentrations are associated with a reduced risk of postnatal HIV transmission. A nested case-control study was conducted within a larger cohort study of HIV-infected women and their infants followed from birth to 24 mo in Lusaka, Zambia. Breast-milk samples collected at 1 mo from 81 HIV-infected women who transmitted via breastfeeding, a random sample of 86 HIV-infected women who did not transmit despite breastfeeding, and 36 uninfected breastfeeding women were selected. Total and specific HMO concentrations were measured by HPLC and compared between groups with adjustment for confounders by using logistic regression. HIV-infected women with total HMOs above the median (1.87 g/L) were less likely to transmit via breastfeeding (OR: 0.45; 95% CI: 0.21, 0.97; P = 0.04) after adjustment for CD4 count and breast-milk HIV RNA concentrations; a trend toward higher concentrations of lacto-N-neotetraose being associated with reduced transmission (OR: 0.49; 95% CI: 0.23, 1.04; P = 0.06) was also observed. The proportion of 3'-sialyllactose (3'-SL) per total HMOs was higher among transmitting than among nontransmitting women (P = 0.003) and correlated with higher plasma and breast-milk HIV RNA and lower CD4 counts. Neither Secretor nor Lewis status distinguished between transmitting and nontransmitting women. Higher concentrations of non-3'-SL HMOs were associated with protection against postnatal HIV transmission independent of other known risk factors. Further study of these novel, potentially anti-HIV components of breast milk is warranted.

Short Communication: Predicting Adverse HIV-Related Outcomes in a Resource-Limited Setting: Use of the Inflammation Marker α1-Acid Glycoprotein

Limited data exist on the use of acute-phase proteins as predictors of HIV-related outcomes. We examined the relationship between postpartum α(1)-acid glycoprotein (AGP) concentrations and HIV-related maternal mortality, mother-to-child transmission, and HIV-free survival among 643 Zimbabwean women. Elevated AGP was significantly associated with a 5.74-fold (p = 0.001) increased risk of maternal death, a 2.39-fold (p = 0.033) increased risk of postnatal transmission, and a marginally significant 1.85-fold (p = 0.087) increased risk of infant infection or death. In a resource-limited setting, AGP may be of utility as an inexpensive prognostic tool for HIV-infected individuals.

Universal antiretroviral therapy among pregnant and postpartum HIV-infected women would improve maternal health and decrease postnatal HIV transmission

In a recent issue of AIDS, the Zvitambo study group from Zimbabwe showed increased post-partum mortality among HIV-infected women with high CD4 count who were not eligible for and not receiving antiretroviral therapy (ART), compared to HIV-uninfected post-partum women from the same population [1]. In the two years post-partum, the adjusted mortality hazard ratio (95% confidence interval) was 7.3 (3.6-15.1) among HIV-infected women with baseline CD4 between 600 and 800 cells/ml, compared to the reference category of HIV uninfected women [1]. The authors therefore argued the case for early ART initiation among all pregnant and post-partum women in Africa, irrespective of CD4 count or treatment eligibility. We entirely agree with this interpretation of their findings, in particular because such a strategy would also contribute to the elimination of paediatric HIV in breastfeeding populations. To prove this point, we combined data from two cohorts in South [2] and West Africa [3] to evaluate mother-to-child transmission (MTCT) risk through breastfeeding [4]. Similar to the Zvitambo trial, maternal ART was unavailable at the time of the study in these two populations. In this pooled analysis, breastfeeding duration was a median of 6.4 months (inter-quartile range: 4.4-12.4), shorter than usually observed in African settings; postnatal transmission rates were thus similarly lower than seen elsewhere. Overall, 70% of these HIV-infected pregnant breastfeeding women had CD4 counts above 350 cells/ml (Table 1), and would therefore not have been eligible for ART for their own health according to the most recently agreed international recommendations [5]. In the absence of ART intervention, the cumulative risk of HIV transmission through breastfeeding in the first 18 months of life was substantial in this group (4.8%), despite there high CD4 count, accounting for 53% of all cases of breastfeeding transmission (the remaining 47% of postnatal transmission cases occurred among women with <350 CD4 cells/ml). Further, even women with baseline CD4 counts above 500 or above 700 cells/ml were at substantial risk of postnatal transmission (Table 1). These findings highlight the crucial need for an antiretroviral-based interventions also among women with higher CD4 counts, so that the risk of HIV transmission can be significantly reduced for all HIV-exposed infants. If ART had been provided to these women with CD4 counts over 350, the expected MTCT rate would have been at least halved, as per European experience [6]. Table 1 18-month postnatal HIV transmission risk among uninfected children at four weeks of age according to different thresholds of maternal antenatal CD4 count. Pooled analysis of the Vertical Transmission Study (South Africa, 2001-2007) and the ANRS 1202 Ditrame ... In the recently released WHO guidelines on the use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants, two options of similar efficacy are offered for women with CD4 count above the 350 CD4 treatment eligibility threshold [7]. Option A consists in providing maternal zidovudine prophylaxis from the second trimester of pregnancy until delivery, followed by daily oral nevirapine to the breastfed infant until all breastfeeding has ceased. Option B consists of the provision of maternal triple antiretroviral prophylaxis (as per ART for treatment) starting from the second trimester of pregnancy until all exposure to breast milk has ended. The new results from the Zvitambo study clearly support the initiation of triple antiretroviral prophylaxis among all pregnant women and continued throughout breastfeeding exposure, following option B, not only to prevent mother-to-child HIV transmission and enable safer breastfeeding practices, but importantly also to improve maternal health. Both eligible and ineligible women would then be receiving the same triple antiretroviral regimen, which would make this universal strategy easier to implement at a population level [8]. However, in a context where all pregnant women would be offered triple antiretroviral regimens, the question of whether and when to stop this intervention in women who are not eligible for ARV treatment according to the current international guidelines is of particular interest. The risk for maternal health of stopping maternal triple ARV prophylaxis after breastfeeding cessation among women with high CD4 count is unknown. Hence, this strategy would need to be assessed in carefully conducted field studies in terms of acceptability, efficiency and maternal and infant safety.

Antiretroviral drugs to prevent breastfeeding HIV transmission

Observational studies and randomized clinical trials demonstrating that antiretroviral prophylaxis of the breastfeeding infant or triple-drug antiretroviral prophylaxis of the lactating mother can significantly affect the risk of postnatal transmission of HIV via breast milk have recently become available. In resource-limited countries, breastfeeding is a cornerstone of infant survival. While shortening the duration of breastfeeding by HIV-infected women reduces postnatal HIV transmission, increasing data suggest this may also decrease overall infant survival. Thus, there is a crucial need for interventions to allow safer and more prolonged breastfeeding. This paper will critically review the results of studies of postnatal antiretroviral prophylaxis to prevent breast milk HIV transmission.

Associations between Breast Milk Viral Load, Mastitis, Exclusive Breast‐Feeding, and Postnatal Transmission of HIV

. Exclusive breast-feeding is protective against postnatal transmission of human immunodeficiency virus (HIV), compared with mixed breast-feeding. Accordingly, exclusive breast-feeding for 6 months is the World Health Organization's recommendation to HIV-infected mothers for whom exclusive replacement feeding is not acceptable, feasible, affordable, safe, or sustainable. The mechanism of exclusive breast-feeding protection is unknown but is hypothesized to be mediated through reduced mastitis. We compared breast milk and plasma specimens of exclusive breast-feeding and mixed breast-feeding HIV- positive mothers archived from the ZVITAMBO trial in which mixed breast-feeding was associated with a 2-fold increased risk of postnatal transmission at 18 months. Plasma HIV load, breast milk HIV load and sodium/potassium ratio were measured as a proxy for subclinical mastitis. Mixed breast-feeding was not associated with mastitis or breast milk HIV load. Mastitis was associated with breast milk HIV load, and this effect increased with increasing maternal plasma HIV load; mastitis was associated with postnatal transmission only when maternal plasma HIV load was high (>3.7 log(10) copies/mL). Initiation of breast-feeding within an hour of delivery was associated with exclusive breast-feeding (adjusted odds ratio, 1.62; 95% confidence interval, 1.02-2.58). Exclusive breast-feeding is associated with reduced postnatal transmission of HIV from mother to child, but this protection is not mediated by reduced mastitis or breast milk HIV load. The deleterious effect of mastitis increases as the mother's plasma HIV load increases.

The Risks of Not Breastfeeding

The Risks of Not Breastfeeding

Effect of early exclusive breastfeeding on morbidity among infants born to HIV-negative mothers in Zimbabwe

BackgroundEarly exclusive breastfeeding (EBF) is recommended by the World Health Organization, but EBF rates remain low throughout the world. For infants born to breastfeeding HIV-positive mothers, early EBF is associated with a lower risk of postnatal transmission than is feeding breast milk together with other liquids or foods. No studies conducted in Africa have reported any benefits of EBF for infants born to HIV-negative women. Objective:The objective was to compare the rate of sick clinic visits by infants aged 43–182 d according to breastfeeding exclusivity [EBF, predominant breastfeeding (PBF), and mixed breastfeeding (MBF)]. Design:We compared rates of all-cause clinic visits and clinic visits related to diarrhea and lower respiratory tract infection (LRTI) among a cohort of 9207 infants of HIV-negative mothers during 2 age intervals: 43–91 and 92–182 d according to exclusivity of breastfeeding. Breastfeeding exclusivity was defined in 2 ways (“ever since birth” and “previous 7 d”) and was assessed at 43 and 91 d. Results:EBF between birth and 3 mo was significantly protective against diarrhea between 3 and 6 mo of age with the “ever since birth” definition [incidence rate ratios (IRRs) of 8.83 (95% CI: 1.07, 65.53) and 8.76 (95% CI: 1.13, 68.09) for PBF and MBF, respectively] and with the “previous 7 d” definition [2.04 (95% CI: 1.11, 3.77) and 2.05 (95% CI: 1.13, 3.72) for PBF and MBF, respectively]. The adverse effect of MBF on LRTI visits was weaker, reaching borderline significance only by the “ever since birth” definition during the 43–91-d interval (IRR: 1.91; 95% CI: 0.99, 3.67). Conclusion:Early EBF is associated with a significant reduction in sick clinic visits, especially those due to diarrhea.

Pregnancy and Optimal Care of HIV‐Infected Patients

Human immunodeficiency virus (HIV) infection during pregnancy is a condition that requires multidisciplinary care. Care must be rendered that is appropriate for both the mother and the fetus. Prevention of mother-to-child transmission of HIV is of paramount concern. To prevent transmission, universal testing for HIV infection in pregnant women is ideal. In the United States and other developed countries, great strides have been made toward decreasing the risk of HIV transmission to infants to <2% with use of a combination of highly active antiretroviral therapy during the antepartum period and during labor and delivery, scheduled cesarean section when appropriate, avoidance of breast-feeding, and 6 weeks of zidovudine prophylaxis for infants. The continuation of antiretroviral therapy after delivery depends on the needs of the mother with regard to treatment of her own health. In resource-limited countries, where simplified and shortened courses of antiretroviral regimens have been used, reduction in mother-to-child transmission has also been shown, although not as effectively as that with highly active antiretroviral therapy. In these settings, exclusive breast-feeding for 6 months is recommended to reduce the risk of postnatal transmission.

Breastfeeding and AIDS in the developing world

In developing countries where replacement feeding is generally not feasible or safe, hundreds of thousands of infants acquire HIV infection during breastfeeding. Data from recently completed studies provide insight into the safety and hazards of different feeding approaches as well as the use of antiretroviral therapy to prevent postnatal transmission. Several studies confirm that the benefits of avoiding or shortening breastfeeding are offset by adverse outcomes in those infants who escape infection. Reductions in HIV transmission achieved with either formula feeding or early weaning are counterbalanced by increases in uninfected child mortality resulting in no net benefit for HIV-free survival. However, exclusive breastfeeding is associated with a significant decrease in HIV transmission risk. Antiretroviral treatment during breastfeeding to the mother or her infant appears to reduce the risk of postnatal transmission. Studies evaluating daily nevirapine to the breastfeeding infant suggest protection during the period of treatment. Similarly, infants born to breastfeeding women receiving antiretroviral therapy are at lower risk of acquiring HIV. While awaiting further studies defining optimal approaches to preventing HIV transmission during breastfeeding, promoting exclusive breastfeeding and assuring antiretroviral treatment for women with advanced HIV disease will likely prevent the majority of needless maternal and infant deaths.

(B1) Candida and Mycotic Infections

Oral candidiasis (OC) is the most common mucosal manifestation of HIV infection. This workshop examined OC and other mycoses associated with HIV infection. Historically, blood CD4 cell numbers were the primary prognosticator for the development of OC. However, a study that statistically evaluated the predictive role of HIV viral load vs. CD4 cell counts revealed viral load to be a stronger predictor for OC. The role of biofilms and antifungal resistance in recalcitrant OC is unclear at present. In general, micro-organisms including yeasts in biofilms are more resistant to antifungals than their planktonic counterparts. When the remaining organisms are eliminated, the few resistant organisms may not be problematic, because they are present in low numbers. Unusual exotic mycoses in HIV-infected patients are more common in patients from the developing than the developed world. These infections may be recurrent and recalcitrant to therapy, be present in multiple and uncommon sites, increase with the progression of HIV disease, and may play a role similar to that of the more common mycoses. Typing and subtyping of yeasts are probably not critical to the clinical management of candidiasis caused by Candida albicans and non-albicans strains, including C. dubliniensis, because it is responsive to antifungal therapy. C. glabrata is probably the only exception. The presence of oral thrush in infants younger than 6 months of age is associated with an increased post-natal transmission risk of HIV infection. Thus, perinatal retroviral therapy should be combined with the treatment of oral thrush to prevent the post-natal acquisition of HIV.

Preventing postnatal transmission of HIV-1 through breast-feeding: modifying infant feeding practices.

Approaches to reducing or preventing the risk of postnatal transmission through breast-feeding include the avoidance of all breast-feeding and the use of exclusive replacement feeds or exclusive breast-feeding for a limited duration with early and rapid cessation of breast-feeding around 4-6 months of age. The efficacy and safety of the latter approach have not been established and studies are in progress to provide further information. In addition, inactivation of HIV in breast milk would allow breast-feeding to continue while reducing the risk of postnatal transmission of HIV and may be usefully applied in certain circumstances, such as for premature infants or while a mother recovers from mastitis. In this review, experience is reported from clinical trials or studies additional to their main objective of assessing rates and risk factors for mother-to-child transmission. This may inform policy, programming, and training options and may be especially valuable in the absence of conclusive data on the efficacy of the interventions to be applied during the breast-feeding period.

Mother-to-child transmission of HIV infection and its prevention.

An estimated 800,000 children acquired HIV-infection in 2002, most as a result of mother-to-child transmission (MTCT), and vertically-acquired HIV infection continues to be of major public health importance. Prevention of MTCT is possible with a combination of interventions including antiretroviral therapy (ART) (usually in highly active combinations), elective caesarean section and avoidance of breastfeeding, and where infected women are identified before or in pregnancy and have access to these interventions, risk of MTCT is now below 1-2%. However, prompt identification of pregnant women with HIV infection remains pressing in many developed countries; additionally, concerns have arisen regarding adherence to complex treatment regimens in pregnancy and the potential impact of HIV drug resistance. More disturbingly, most HIV-infected women live in developing countries where many pregnant women even when tested do not return for their HIV results for a variety of reasons including stigma, and where most, if not all, strategies for prevention of MTCT have been of limited accessibility and/or feasibility. However, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and other initiatives including pharmaceutical companies' donation programmes and generic antiretroviral drug production have made prevention of MTCT in resource-poor settings an increasingly realistic goal, coupled with new evidence from clinical trials on the efficacy of abbreviated regimens of antiretroviral prophylaxis, including combination therapy, to prevent MTCT. Research is additionally focussing on reducing the risk of postnatal transmission through breastfeeding, with exclusive breastfeeding, early cessation and antiretroviral prophylaxis to breastfeeding women or breastfed infants under investigation. However, the key to prevention of paediatric HIV infections is adequate prevention of infection in women of reproductive age.

Mother-to-child transmission of hepatitis C virus infection.

The prevalence of hepatitis C virus (HCV) infection among pregnant women in Europe is generally below 2%. Although women with a history of parenteral exposures or injecting drug use are at an increased risk of infection, a substantial proportion of infected women do not report any risk factors. Targeted screening is thus not recommended. The risk of mother-to-child, or vertical, transmission of HCV is about 5% overall but can be as high as 15%, depending on maternal HIV infection status and HCV RNA viral load. Larger studies are needed to confirm or refute the potential protective effect of elective cesarean section delivery. However, for HCV-positive women who are co-infected with HIV, elective cesarean section delivery is associated with a reduced risk of vertical transmission of HIV as well as HCV. The risk of postnatal transmission through breastfeeding cannot be excluded but is likely to be low for most HCV-infected women. The long-term natural history of vertically acquired HCV needs further elucidation and the efficacy of potential therapies for infected children need to be evaluated in randomized controlled trials.