High Incidence Rates of Early-onset Bacterial Sepsis in Infants Born in Two Brazilian Maternities: A 15-Year Retrospective Analysis.

BACKGROUND: Data on the burden and etiology of neonatal early-onset bacterial sepsis (EOBS) in low-to-middle-income countries are scarce. Surveillance is critical for optimizing prevention and treatment strategies. We aimed to estimate the incidence of EOBS in 2 large Brazilian cohorts of neonates. METHODS: Data were retrospectively obtained from 33,794 neonates born between 2009 and 2017 at low-risk (n = 17,981) and high-risk maternity centers (n = 15,813). Blood cultures were taken within 72 hours of life from neonates with perinatal risk factors for EOBS or suspected EOBS. A positive blood culture for a pathogenic microorganism and a compatible clinical evolution confirmed the diagnosis of EOBS. RESULTS: One-third of the infants born from high-risk and 18.5% from low-risk maternities were investigated for EOBS. Overall, EOBS was more incident in neonates born in the high-risk facilities [66 cases or 4.2/1000 (95% CI: 3.2-5.3)] than in the low-risk facilities [24 cases or 1.3/1000 (95% CI: 0.9-2.0)]. The incidence rate of EOBS increased with decreasing gestational age (<32 weeks: 20.5/1000; 32-36 weeks: 5.6/1000; ≥37 weeks: 1.5/1000). Group B Streptococcus (GBS) was the agent more frequently identified in high-risk and low-risk maternities: 1.8/1000 (95% CI: 1.1-2.4) and 0.4/1000 (95% CI: 0.2-0.9), respectively. EOBS's overall case fatality rate was 17.8% for all the agents and 22% for GBS. CONCLUSIONS: EOBS remains unacceptably high and is frequently fatal in preterm and term infants cared for in high- or low-risk maternities. Because GBS has emerged as the most frequent causative agent, preventive strategies are urgently needed.

Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.

Maternal immunization in women living with HIV.

Thanks to widespread use of antiretroviral therapy worldwide, women living with HIV (WLWH) are becoming pregnant and giving birth to HIV-exposed but uninfected (HEU) newborns. Both pregnancy and HIV infection-related factors such as low CD4+ T-cell count or uncontrolled viral load increase the risk of severe infections such as influenza, COVID-19, and others, making maternal immunization a valuable tool to decrease maternal morbidity among WLWH. Vaccines administered during pregnancy may also benefit the health of HEU infants. Indeed, HEU infants suffer from higher risk of morbidity of infectious origin, including respiratory syncytial virus (RSV), group B streptococcus (GBS), pneumococcus and pertussis infections. Maternal pertussis immunization is recommended in various high-income countries but not in many low-middle income countries where HIV prevalence is higher. GBS and RSV vaccines to be administered during pregnancy are currently in late-phase clinical trials in HIV-uninfected women and could represent a valuable tool to decrease morbidity during infancy. Decreased transfer of vaccine-specific IgG, accelerated waning of vaccine-induced antibody responses, linked to persistent maternal immune activation, and blunting of infant immune response to vaccines could hamper vaccine effectiveness among WLWH and HEU infants. Vaccine hesitancy could limit benefits of maternal immunization and strategies to tackle vaccine hesitancy should be part of HIV routine care. The aim of this review is to summarize the current knowledge regarding the immunogenicity and efficacy of available and upcoming vaccines recommended during pregnancy of WLWH.

Incidence of Respiratory Syncytial Virus-Associated Lower Respiratory Tract Illness in Infants in Low- and Middle-Income Regions During the Coronavirus Disease 2019 Pandemic.

Background: Incidence data of respiratory syncytial virus-associated lower respiratory tract illness (RSV-LRTI) are sparse in low- and middle-income countries (LMICs). We estimated RSV-LRTI incidence rates (IRs) in infants in LMICs using World Health Organization case definitions. Methods: This prospective cohort study, conducted in 10 LMICs from May 2019 to October 2021 (largely overlapping with the coronavirus disease 2019 [COVID-19] pandemic), followed infants born to women with low-risk pregnancies for 1 year from birth using active and passive surveillance to detect potential LRTIs, and quantitative reverse-transcription polymerase chain reaction on nasal swabs to detect RSV. Results: Among 2094 infants, 32 (1.5%) experienced an RSV-LRTI (8 during their first 6 months of life, 24 thereafter). Seventeen (0.8%) infants had severe RSV-LRTI and 168 (8.0%) had all-cause LRTI. IRs (95% confidence intervals [CIs]) of first RSV-LRTI episode were 1.0 (.3-2.3), 0.8 (.3-1.5), and 1.6 (1.1-2.2) per 100 person-years for infants aged 0-2, 0-5, and 0-11 months, respectively. IRs (95% CIs) of the first all-cause LRTI episode were 10.7 (8.1-14.0), 11.7 (9.6-14.0), and 8.7 (7.5-10.2) per 100 person-years, respectively. IRs varied by country (RSV-LRTI: 0.0-8.3, all-cause LRTI: 0.0-49.6 per 100 person-years for 0- to 11-month-olds). Conclusions: RSV-LRTI IRs in infants in this study were relatively low, likely due to reduced viral circulation caused by COVID-19-related nonpharmaceutical interventions. Clinical Trials Registration: NCT03614676.

Gamma variant vertically transmitted from a mild symptomatic pregnant woman associated with fatal neonatal COVID.

Herein we describe a mild symptomatic real-time reverse transcriptase- polymerase chain reaction-confirmed coronavirus 2 (SARS-CoV-2) infection in a pregnant woman who gave birth to a preterm infant, 32 weeks gestational age. The neonate was immediately isolated after delivery and developed severe respiratory disease that progressed to multisystem inflammatory syndrome and death on the seventh day of life. Genome sequencing detected the P.1 (gamma) variant in samples obtained at hospital admission (mother) and on the first (10h) and 13th days of life (neonate). Complete homology (mother's and newborn's sequences) confirmed vertical transmission. To our knowledge, this is the first report of vertically-transmitted SARS-CoV-2 P.1 (gamma) variant in a mild symptomatic infection in pregnancy associated with fatal COVID in a neonate.

Gamma variant vertically transmitted from a mild symptomatic pregnant woman associated with fatal neonatal COVID

ABSTRACT Herein we describe a mild symptomatic real-time reverse transcriptase- polymerase chain reaction-confirmed coronavirus 2 (SARS-CoV-2) infection in a pregnant woman who gave birth to a preterm infant, 32 weeks gestational age. The neonate was immediately isolated after delivery and developed severe respiratory disease that progressed to multisystem inflammatory syndrome and death on the seventh day of life. Genome sequencing detected the P.1 (gamma) variant in samples obtained at hospital admission (mother) and on the first (10h) and 13th days of life (neonate). Complete homology (mother's and newborn's sequences) confirmed vertical transmission. To our knowledge, this is the first report of vertically-transmitted SARS-CoV-2 P.1 (gamma) variant in a mild symptomatic infection in pregnancy associated with fatal COVID in a neonate.

Cranial US in Infants Exposed to Zika Virus: The NATZIG Cohort.

Background Studies addressing neuroimaging findings as primary outcomes of congenital Zika virus infection are variable regarding inclusion criteria and confirmatory laboratory testing. Purpose To investigate cranial US signs of prenatal Zika virus exposure and to describe frequencies of cranial US findings in infants exposed to Zika virus compared to those in control infants. Materials and Methods In this single-center prospective cohort study, participants were enrolled during the December 2015-July 2016 outbreak of Zika virus infection in southeast Brazil (Natural History of Zika Virus Infection in Gestation cohort). Eligibility criteria were available cranial US and laboratory findings of maternal Zika virus infection during pregnancy confirmed with RNA polymerase chain reaction testing (ie, Zika virus-exposed infants). The control group was derived from the Zika in Infants and Pregnancy cohort and consisted of infants born to asymptomatic pregnant women who tested negative for Zika virus infection during pregnancy. Two radiologists who were blinded to the maternal Zika virus infection status independently reviewed cranial US scans from both groups and categorized them as normal findings, Zika virus-like pattern, or mild findings. Associations between cranial US findings and prenatal Zika virus exposure were assessed with univariable analysis. Results Two hundred twenty Zika virus-exposed infants (mean age, 53.3 days ± 71.1 [standard deviation]; 113 boys) and born to 219 mothers infected with Zika virus were included in this study and compared with 170 control infants (mean age, 45.6 days ± 45.8; 102 boys). Eleven of the 220 Zika virus-exposed infants (5%), but no control infants, had a Zika virus-like pattern at cranial US. No difference in frequency of mild findings was observed between the groups (50 of 220 infants [23%] vs 44 of 170 infants [26%], respectively; P = .35). The mild finding of lenticulostriate vasculopathy, however, was nine times more frequent in Zika virus-exposed infants (12 of 220 infants, 6%) than in control infants (one of 170 infants, 1%) (P = .01). Conclusion Lenticulostriate vasculopathy was more common after prenatal exposure to Zika virus, even in infants with normal head size, despite otherwise overall similar frequency of mild cranial US findings in Zika virus-exposed infants and in control infants. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Benson in this issue.

Zika Brazilian Cohorts (ZBC) Consortium: Protocol for an Individual Participant Data Meta-Analysis of Congenital Zika Syndrome after Maternal Exposure during Pregnancy.

Despite great advances in our knowledge of the consequences of Zika virus to human health, many questions remain unanswered, and results are often inconsistent. The small sample size of individual studies has limited inference about the spectrum of congenital Zika manifestations and the prognosis of affected children. The Brazilian Zika Cohorts Consortium addresses these limitations by bringing together and harmonizing epidemiological data from a series of prospective cohort studies of pregnant women with rash and of children with microcephaly and/or other manifestations of congenital Zika. The objective is to estimate the absolute risk of congenital Zika manifestations and to characterize the full spectrum and natural history of the manifestations of congenital Zika in children with and without microcephaly. This protocol describes the assembly of the Consortium and protocol for the Individual Participant Data Meta-analyses (IPD Meta-analyses). The findings will address knowledge gaps and inform public policies related to Zika virus. The large harmonized dataset and joint analyses will facilitate more precise estimates of the absolute risk of congenital Zika manifestations among Zika virus-infected pregnancies and more complete descriptions of its full spectrum, including rare manifestations. It will enable sensitivity analyses using different definitions of exposure and outcomes, and the investigation of the sources of heterogeneity between studies and regions.

Persistence of Anti-ZIKV-IgG over Time Is Not a Useful Congenital Infection Marker in Infants Born to ZIKV-Infected Mothers: The NATZIG Cohort.

Confirming ZIKV congenital infection is challenging because viral RNA is infrequently detected. We compared the presence of anti-ZIKV-IgM and the persistence of anti-ZIKV-IgG antibodies over 18 months in two cohorts of infants born to ZIKV-infected mothers: Cohort one: 30 infants with typical microcephaly or major brain abnormalities (Congenital Zika Syndrome-CZS); Cohort two: 123 asymptomatic infants. Serum samples obtained within 6 months of age were tested for anti-ZIKV-IgM. Anti-ZIKV-IgG was quantified in sequential samples collected at birth, 3-6 weeks, 3, 6, 12, and 18 months. ZIKV-RNA was never detected postnatally. Anti-ZIKV-IgM antibodies were detected at least once in 15/25 (60.0%; 95%CI: 38.7-78.9) infants with CZS and in 2/115 (1.7%; 95%CI: 0.2-6.1) asymptomatic infants. Although anti-ZIKV-IgG was always positive within 3-6 weeks of age, IgG levels decreased similarly over time in both cohorts. IgG levels decreased similarly in ZIKV-IgM-positive and ZIKV-IgM-negative CZS infants. Differently from other congenital infections, IgM would fail to diagnose 40% of severely symptomatic infants, and the persistence of IgG is not a useful marker for discriminating congenital infection among infants exposed to maternal ZIKV infection.

Natural History of Congenital Cytomegalovirus Infection in Highly Seropositive Populations.

Maternal preconceptional cytomegalovirus (CMV) immunity does not protect the fetus from acquiring congenital CMV infection (cCMV). Nonprimary infections due to recurrence of latent infections or reinfection with new virus strains during pregnancy can result in fetal infection. Because the prevalence of cCMV increases with increasing maternal CMV seroprevalence, the vast majority of the cases of cCMV throughout the world follow nonprimary maternal infections and is more common in individuals of lower socioeconomic background. Horizontal exposures to persons shedding virus in bodily secretions (young children, sexual activity, household crowding, low income) probably increase the risk of acquisition of an exogenous nonprimary CMV infection and fetal transmission. In addition, more frequent acquisition of new antibody reactivities in transmitter mothers suggest that maternal reinfection by new viral strains could be a major source of congenital infection in such populations. However, the exact frequency of CMV nonprimary infection in seroimmune women during pregnancy and the rate of intrauterine transmission in these women are yet to be defined. Usually, the birth prevalence of cCMV is high (≥7:1000) in highly seropositive populations. There is increasing evidence that the frequency and severity of the clinical and laboratory abnormalities in infants with congenital CMV infection born to mothers with nonprimary CMV infection are similar to infants born after a primary maternal infection. This is particularly true for sensorineural hearing loss, which contributes to one third of all early-onset hearing loss in seropositive populations. This brief overview will discuss the need for more research to better clarify the natural history of cCMV in highly seropositive populations, which, in almost all populations, remains incompletely defined.

Is the mixture of human cytomegalovirus genotypes frequent in infants with congenital infection at birth in a high seroprevalence population?

It is still not well known, in a population with high human cytomegalovirus (HCMV) seroprevalence, whether a child with congenital infection harbors multiple viral strains at birth, and whether the prolonged viral excretion in these children is secondary to the persistence of the same viral strain. To verify the genomic diversity of HCMV detected in congenitally infected children, the nucleotide viral sequences from urine and/or saliva obtained at birth from 14 newborns with congenital infection and breast milk obtained from mothers of 5 of these children were analyzed. Among the 14 children, 10 had sequential samples until the median age of 10 months. The viral nucleotide sequences in the breast milk were compared with those identified in the respective children at birth. The differentiation of viral strains was based on the variability of 3 regions of viral genes (UL55/gB, UL144, and UL73/gN). In 13/14 children (92.8%), a single genotype was observed at birth. Different viral genotypes were found in 1 child (7.2%). Among the sequential samples from 10 children, the same genotype obtained at birth was detected in 9/10 (90%), and in 1 of them (10%), a genotype change in the urine was found. More than 1 HCMV strain in milk was observed in 2 mothers (2/5, 40%). In a population with high seroprevalence, a single genotype was found in the majority of infected children. Reinfection did not frequently occur in the first months of life. Maternal reinfection does not seem to be a rare event in transmitter mothers.

Incidence, Risk Factors, and Morbidity of Acquired Postnatal Cytomegalovirus Infection Among Preterm Infants Fed Maternal Milk in a Highly Seropositive Population.

BACKGROUND: In preterm infants cytomegalovirus (CMV) infection acquired through maternal milk has been related to morbidity. However, infants who may receive higher titers of protective antibodies from highly seropositive mothers have not been studied in detail. METHODS: A cohort of 188 ≤30-week-old infants was monitored from admission to discharge. CMV-DNA, hematology, liver enzymes, neutralizing antibodies, and CMV-DNA-lactia were tested periodically. RESULTS: Mothers of 157 infants (83.5%) were CMV-seropositive. A total of 24/157 (15.3%) infants became infected (95% confidence interval [CI], 9.8-22.6), particularly those of lower gestational age (GA; relative risk [RR], 2.32; 95% CI, 1.01-5.34 for 23-26 weeks). Low (<1:64) neutralizing antibody titers were similarly detected in CMV-infected and uninfected infants. Mean DNA-lactia in mothers was higher in CMV-infected than in uninfected infants (5.34 log vs 4.60 log). Clinical findings suggestive of CMV disease were similar in CMV-infected (50.0%) and CMV-uninfected (51.1%) infants. Although transitory, >2 laboratory test abnormalities occurred more frequently among CMV-infected (39.1%) than CMV-uninfected (2.1%) infants. More severe stages of retinopathy of prematurity (ROP) were found among CMV-infected infants (adjusted RR, 2.51; 95% CI, 1.07-5.91). Although deaths were more frequent among infected infants, none of the deaths could be directly attributed to CMV. CONCLUSIONS: Postnatal CMV infection acquired by exposure to raw maternal milk is very frequent among extremely premature newborns, being facilitated by high DNA-lactia and lower GA, regardless of maternally acquired neutralizing antibody levels. The association with advanced stages of ROP is a concern and needs to be further explored in larger studies.

Development and optimization of a sensitive TaqMan® real-time PCR with synthetic homologous extrinsic control for quantitation of Human cytomegalovirus viral load.

Human cytomegalovirus (Human herpesvirus 5, HCMV) causes frequent asymptomatic infections in the general population. However, in immunosuppressed patients or congenitally infected infants, HCMV is related to high morbidity and mortality. In such cases, a rapid viral detection is crucial for monitoring the clinical outcome and the antiviral treatment. In this study, we optimized a sensitive biplex TaqMan® real-time PCR for the simultaneous detection and differentiation of a partial HCMV UL97 sequence and homologous extrinsic control (HEC) in the same tube. HEC was represented by a plasmid containing a modified HCMV sequence retaining the original primer binding sites, while the probe sequence was substituted by a phylogenetically divergent one (chloroplast CF0 subunit plant gene). It was estimated that the optimal HEC concentration, which did not influence the HCMV amplification is 1,000 copies/reaction. The optimized TaqMan® PCR demonstrated high analytical sensitivity (6.97 copies/reaction, CI = 95%) and specificity (100%). Moreover, the reaction showed adequate precision (repeatability, CV = 0.03; reproducibility, CV = 0.0027) and robustness (no carry-over or cross-contamination). The diagnostic sensitivity (100%) and specificity (97.8%) were adequate for the clinical application of the molecular platform. The optimized TaqMan® real-time PCR is suitable for HCMV detection and quantitation in predisposed patients and monitoring of the applied antiviral therapy. J. Med. Virol. 88:1604-1612, 2016. © 2016 Wiley Periodicals, Inc.

Vitamin A, vitamin E, iron and zinc status in a cohort of HIV-infected mothers and their uninfected infants

Introduction We hypothesized that nutritional deficiency would be common in a cohort of postpartum, human immunodeficiency virus (HIV)-infected women and their infants. Methods Weight and height, as well as blood concentrations of retinol, α-tocopherol, ferritin, hemoglobin, and zinc, were measured in mothers after delivery and in their infants at birth and at 6-12 weeks and six months of age. Retinol and α-tocopherol levels were quantified by high performance liquid chromatography, and zinc levels were measured by atomic absorption spectrophotometry. The maternal body mass index during pregnancy was adjusted for gestational age (adjBMI). Results Among the 97 women 19.6% were underweight. Laboratory abnormalities were most frequently observed for the hemoglobin (46.4%), zinc (41.1%), retinol (12.5%) and ferritin (6.5%) levels. Five percent of the women had mean corpuscular hemoglobin concentrations < 31g/dL. The most common deficiency in the infants was α-tocopherol (81%) at birth; however, only 18.5% of infants had deficient levels at six months of age. Large percentages of infants had zinc (36.8%) and retinol (29.5%) deficiencies at birth; however, these percentages decreased to 17.5% and 18.5%, respectively, by six months of age. No associations between infant micronutrient deficiencies ...

Vitamin A, vitamin E, iron and zinc status in a cohort of HIV-infected mothers and their uninfected infants.

UNLABELLED: Introduction: We hypothesized that nutritional deficiency would be common in a cohort of postpartum, human immunodeficiency virus (HIV)-infected women and their infants. METHODS: Weight and height, as well as blood concentrations of retinol, α-tocopherol, ferritin, hemoglobin, and zinc, were measured in mothers after delivery and in their infants at birth and at 6-12 weeks and six months of age. Retinol and α-tocopherol levels were quantified by high performance liquid chromatography, and zinc levels were measured by atomic absorption spectrophotometry. The maternal body mass index during pregnancy was adjusted for gestational age (adjBMI). RESULTS: Among the 97 women 19.6% were underweight. Laboratory abnormalities were most frequently observed for the hemoglobin (46.4%), zinc (41.1%), retinol (12.5%) and ferritin (6.5%) levels. Five percent of the women had mean corpuscular hemoglobin concentrations < 31g/dL. The most common deficiency in the infants was α-tocopherol (81%) at birth; however, only 18.5% of infants had deficient levels at six months of age. Large percentages of infants had zinc (36.8%) and retinol (29.5%) deficiencies at birth; however, these percentages decreased to 17.5% and 18.5%, respectively, by six months of age. No associations between infant micronutrient deficiencies and either the maternal adjBMI category or maternal micronutrient deficiencies were found. CONCLUSIONS: Micronutrient deficiencies were common in HIV-infected women and their infants. Micronutrient deficiencies were less prevalent in the infants at six months of age. Neither underweight women nor their infants at birth were at increased risk for micronutrient deficiencies.

Birth prevalence and characteristics of congenital toxoplasmosis in Sergipe, North-east Brazil.

OBJECTIVES: To estimate, by neonatal screening, the birth prevalence of congenital toxoplasmosis among live-born infants in Sergipe state, Brazil, and to investigate the clinical features of affected infants. METHODS: Dried blood spot specimens obtained from 15 204 neonates were assayed for the presence of anti-T. gondii IgM antibodies. Duplicate retesting was done in infants with positive and borderline results. Confirmatory testing in peripheral blood samples consisted of testing for anti-T. gondii IgG and IgM in infants and mothers. Those with possible congenital toxoplasmosis were evaluated and followed up to a median age of 20 months. Congenital infection was confirmed in the presence of persisting anti-T. gondii IgG antibodies beyond 12 months of age. All infants with confirmed infection were treated with pyrimethamine, sulfadiazine and folinic acid for 1 year. RESULTS: Fifty-three infants had detectable IgM in dried blood spot specimens. Confirmatory testing was reactive in 39/50, of which, 38 completed follow-up. Six of 15 204 newborns were diagnosed with congenital toxoplasmosis, resulting in an estimated birth prevalence of four per 10 000 [CI 95% 1.4-8.0]. Four infants (67%) showed signs of congenital toxoplasmosis in their first year of life; three (75%) had retinochoroidal scars, and one had cerebral calcifications. Two infants remained asymptomatic until 20 months of age. CONCLUSIONS: The birth prevalence of congenital toxoplasmosis is high in the Brazilian state of Sergipe, with most of the infants showing ocular lesions. Preventive measures are strongly warranted.

Congenital cytomegalovirus infection as a cause of sensorineural hearing loss in a highly immune population.

BACKGROUND: The burden of congenital cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) in populations with CMV seroprevalence approaching 100% is unknown. The purpose of this study was to assess the rate, associated factors, and predictors of SNHL in CMV-infected infants identified by newborn screening in a highly seropositive maternal population. METHODS: Newborns with positive saliva CMV-DNA that was confirmed by virus isolation in the first 2 weeks of life were enrolled in a prospective follow-up study to monitor hearing outcome. RESULTS: Of 12,195 infants screened, 121 (1%) were infected with CMV and 12 (10%) had symptomatic infection at birth. Hearing function could be assessed in 102/121 children who underwent at least one auditory brainstem evoked response testing at a median age of 12 months. SNHL was observed in 10/102 (9.8%; 95% confidence interval: 5.1-16.7) children. Median age at the latest hearing evaluation was 47 months (12-84 months). Profound loss (>90 dB) was found in 4/5 children with bilateral SNHL while all 5 children with unilateral loss had moderate to severe deficit. The presence of symptomatic infection at birth (odds ratio, 38.1; 95% confidence interval: 1.6-916.7) was independently associated with SNHL after adjusting for intrauterine growth restriction, gestational age, gravidity, and maternal age. Among 10 infants with SNHL, 6 (60%) were born to mothers with nonprimary CMV infection. CONCLUSIONS: Even in populations with near universal immunity to CMV, congenital CMV infection is a significant cause of SNHL demonstrating the importance of CMV as a major cause of SNHL in children worldwide. As in other populations, SNHL is more frequently observed in symptomatic CMV infection.

Lopinavir/ritonavir dosing during pregnancy in Brazil and maternal/infant laboratory abnormalities.

OBJECTIVES: To describe laboratory abnormalities among HIV-infected women and their infants with standard and increased lopinavir/ritonavir (LPV/r) dosing during the third trimester of pregnancy. METHODS: We evaluated data on pregnant women from NISDI cohorts (2002-2009) enrolled in Brazil, who received at least 28 days of LPV/r during the third pregnancy trimester and gave birth to singleton infants. RESULTS: 164 women received LPV/r standard dosing [(798/198 or 800/200 mg/day) (Group 1)] and 70 increased dosing [(> 800/200 mg/day) (Group 2)]. Group 1 was more likely to have advanced clinical disease and to use ARVs for treatment, and less likely to have CD4 counts > 500 cells/mm³. Mean plasma viral load was higher in Group 2. There were statistically significant, but not clinically meaningful, differences between groups in mean AST, ALT, cholesterol, and triglycerides. The proportion of women with Grade 3 or 4 adverse events was very low, with no statistically significant differences between groups in severe adverse events related to ALT, AST, total bilirubin, cholesterol, or triglycerides. There were statistically significant, but not clinically meaningful, differences between infant groups in ALT and creatinine. The proportion of infants with Grade 3 or 4 adverse events was very low, and there were no statistically significant differences in severe adverse events related to ALT, AST, BUN, or creatinine. CONCLUSION: The proportions of women and infants with severe laboratory adverse events were very low. Increased LPV/r dosing during the third trimester of pregnancy appears to be safe for HIV-infected women and their infants.