Gross motor function in children with Congenital Zika Syndrome from Rio de Janeiro, Brazil.

Congenital Zika Syndrome (CZS) is characterized by many impairments especially in the central nervous system, potentially compromising neurodevelopment and causing significant morbidity in affected children. The aim was to assess gross motor function in children with CZS. This was a cross-sectional investigation nested within a prospective cohort study of children with CZS based in a Brazilian referral hospital in Rio de Janeiro. Between March/2017 and February/2018, we performed gross motor function assessments using the Gross Motor Function Classification (GMFCS) and the Gross Motor Function Measure (GMFM), estimating the mean and standard deviation of GMFM scores among GMFCS groups. The study sample included 72 children, with a median age of 13 months (7-25). Of these, 63 (87.5%) had severe motor impairment, 3 (4%) had moderate impairment, and 6 (8%) had mild impairment. The mean GMFM score for each group was respectively 11.6, 26.1, and 81.6, with statistically significant differences (p-value < 0.001). Severely affected children only achieved head control in the sitting posture when supported. Children with milder forms were able to develop walking skills.Conclusion: Most children with CZS have major motor disabilities and a poor prognosis. Better understanding of limitations and functionality in children with CZS can serve as a prognostic guide in their management. What is Known: • Severe motor impairment was present in 63 (87.5%) children with CZS. • The degree of neurological impairment was inversely associated with motor performance. What is New: • Microcephaly was more frequent among children with severe gross motor function impairment. • Children with CZS have major motor disabilities and a poor prognosis.

Middle Cerebral Artery Dopplers and Abnormal Neonatal Outcomes among Pregnant Women with Zika Virus Infection.

OBJECTIVE: The aim of this study was to investigate the role of middle cerebral artery (MCA) Doppler measurements for the prediction of abnormal neonatal outcomes in pregnancies affected by Zika virus (ZIKV). METHODS: Secondary analysis of a prospective cohort of pregnant women diagnosed with ZIKV infection from September 2015 to December 2016 at a single regional referral center. Ultrasonography with measurements of MCA peak systolic velocity (PSV), PSV multiples of the median (MoM) for gestational age, and pulsatility index (PI) were collected. The primary outcome was a composite abnormal neonatal outcome. MCA Doppler values of normal and abnormal neonatal outcomes were compared with Wilcoxon rank sum test. The predictive value of MCA Dopplers for development of abnormal neonatal outcome was calculated by logistic regression. RESULTS: One-hundred twenty-seven ZIKV-positive pregnancies with MCA Doppler measurements and known neonatal outcomes were included. Of the 132 neonates, 66 (50%) had an abnormal neonatal outcome. Lower MCA PSV (p = 0.027) and PSV MoM (p = 0.008) were associated with abnormal neonatal outcomes. There was no significant difference in MCA PI. Abnormal neonatal outcomes had lower MCA PSV by 5.36 cm/s (95% confidence interval [CI]: 0.95-9.77, p = 0.018) and lower MCA PSV MoM by 0.13 (95% CI: 0.05-0.22, p = 0.002). MCA PSV of 30 cm/s had a 65% predicted probability of an abnormal neonatal outcome (95% CI: 51-79%). CONCLUSION: In ZIKV-infected pregnancies, lower MCA PSV and PSV MoM measurements were seen with abnormal neonatal outcomes. This may represent a physiologic response to fetal ZIKV infection. Evaluation of MCA Dopplers may be of clinical utility in the surveillance of ZIKV-affected pregnancies. KEY POINTS: · Significantly lower MCA PSV is associated with abnormal neonatal outcomes in ZIKV pregnancies.. · Lower MCA PSV may reflect the underlying neuropathology of ZIKV exposure on the fetus.. · There is potential utility for MCA Doppler evaluation in antepartum surveillance of ZIKV pregnancies..

ZIKA Virus Neutralizing Antibody Kinetics in Antenatally Exposed Infants.

BACKGROUND: Zika virus (ZIKV) is associated with severe congenital abnormalities and laboratory diagnosis of antenatal infection is difficult. Here we evaluated ZIKV neutralizing antibody (nAb) kinetics in infants born to mothers with PCR-confirmed ZIKV infection during pregnancy. METHODS: Neonates (n = 98) had serum specimens tested repeatedly for ZIKV nAb over the first 2 years of life using virus neutralization test (VNT). ZIKV neonatal infection was confirmed by RT-PCR in blood or urine and/or presence of ZIKV IgM antibodies, and results were correlated with infant clinical features. RESULTS: Postnatal laboratory evidence of ZIKV vertical transmission was obtained for 60.2% of children, while 32.7% exhibited clinical abnormalities. Congenital abnormalities were found in 37.3% of children with confirmed ZIKV infection and 31.0% of children without confirmed infection (P = .734). All but 1 child displayed a physiologic decline in ZIKV nAb, reflecting maternal antibody decay, despite an early ZIKV-IgM response in one-third of infants. CONCLUSIONS: Infants with antenatal ZIKV exposure do not develop ZIKV nAb despite an early IgM response. Therefore, ZIKV VNT in children is not useful for diagnosis of congenital infection. In light of these findings, it remains to be determined if children infected in utero are potentially susceptible to reinfection.

Early Clinical Infancy Outcomes for Microcephaly and/or Small for Gestational Age Zika-Exposed Infants.

BACKGROUND: Zika-exposed infants with microcephaly (proportional or disproportional) and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.Antenatal Zika virus (ZIKV) exposure may lead to adverse infant outcomes including microcephaly and being small for gestational age (SGA). ZIKV-exposed infants with a diagnosis of microcephaly (proportional [PM] or disproportional [DM]) or SGA at birth were evaluated with anthropometric measurements and health outcomes. METHODS: Infants had laboratory-confirmed ZIKV exposure in Brazil. PM, DM, or SGA classification was based on head circumference and weight. First-year growth parameters and clinical outcomes were recorded with analyses performed. RESULTS: Among the 156 ZIKV-exposed infants, 14 (9.0%) were SGA, 13 (8.3%) PM, 13 (8.3%) DM, and 116 (74.4%) were neither SGA nor had microcephaly (NSNM). High rates of any neurologic, ophthalmologic, and hearing abnormalities were observed for PM (100%), DM (100%), and SGA (42.9%) vs NSNM infants (18.3%; P <.001); odds ratio [OR], 3.4 (95% confidence interval [CI], 1.1-10.7) for SGA vs NSNM. Neuroimaging abnormalities were seen in 100% of PM and DM and in 42.9% of SGA vs NSNM infants 16%; (P <.001); OR 3.9 (95% CI, 1.2-12.8) for SGA vs NSNM. Growth rates by z score, particularly for microcephaly infants, were poor after birth but showed improvement beyond 4 months of life. CONCLUSIONS: ZIKV-exposed infants with microcephaly (PM and DM) had similarly high rates of adverse outcomes but showed improvement in growth measurements beyond 4 months of life. While SGA infants had fewer adverse outcomes compared with microcephaly infants, notable adverse outcomes were observed in some; their odds of having adverse outcomes were 3 to 4 times greater compared to NSNM infants.Zika-exposed infants with microcephaly, irrespective of being proportional or disproportional, and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.

Zika Virus Infection in Pregnant Women in Rio de Janeiro.

BACKGROUND: Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. METHODS: We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. RESULTS: A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester). CONCLUSIONS: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).

Retrospective analysis of risk factors and gaps in prevention strategies for mother-to-child HIV transmission in Rio de Janeiro, Brazil.

BACKGROUND: Despite great progress made in methods to prevent mother-to-child transmission of HIV (MTCT), delivery and uptake of these measures remains a challenge in many countries. Although the Brazilian Ministry of Health aimed to eliminate MTCT by 2015, infection still occured in 15-24% of infants born to HIV-infected mothers. We sought to identify remaining factors that constrain MTCT elimination. METHODS: We conducted a retrospective, matched case-control study by reviewing hospital charts of infants born to HIV-infected mothers between 1997 and 2014 at three MTCT reference hospitals in the Rio de Janeiro metropolitan area. Cases were defined as HIV-exposed children with two positive HIV tests before 18 months of age; controls were defined as HIV-exposed children with two negative HIV tests before 18 months of age. We performed bivariate and MTCT cascade analyses to identify risk factors for MTCT and gaps in prevention services. RESULTS: We included 435 infants and their mothers (145 cases, 290 controls). Bivariate analyses of MTCT preventative care (PMTCT) indicated that cases were less likely to complete all individual measures in the antenatal, delivery, and postnatal period (p < 0.05). Assessing completion of the PMTCT cascade, the sequential steps of PMTCT interventions, we found inadequate retention in care among both cases and controls, and cases were significantly less likely than controls to continue receiving care throughout the cascade (p < 0.05). Motives for incompletion of PMTCT measures included infrastructural issues, such as HIV test results not being returned, but were most often due to lack of care-seeking. Over the course of the study period, PMTCT completion improved, although it remained below the 95% target for antenatal care, HIV testing, and antenatal ART set by the WHO. Adding concern, evaluation of co-infections indicated that case infants were also more likely to have congenital syphilis (OR: 4.29; 95% CI: 1.66 to 11.11). CONCLUSIONS: While PMTCT coverage has improved over the years, completion of services remains insufficient. Along with interventions to promote care-seeking behaviour, increased infrastructural support for PMTCT services is needed to meet the HIV MTCT elimination goal in Brazil as well as address rising national rates of congenital syphilis.

Zika virus infection in children: epidemiology and clinical manifestations.

PURPOSE: The purpose of this review is to comprehensively review Congenital Zika Syndrome in regard to their epidemiology and clinical manifestations. METHODS: This subject review of congenital Zika syndrome was composed after conducting a thorough review of the available literature on this topic using PubMed and other primary sources. RESULTS: The first epidemic of Zika virus infection in Brazil was followed by an unexpected sharp increase in the incidence of infants born with microcephaly and the description of a new disease, the congenital Zika syndrome. This review focuses on the epidemiological and clinical aspects of Zika infection in children. We conducted a brief historical account of the virus description in 1947, the rare cases of Zika infection occurring up to 2007, and the first epidemics in the Pacific between 2007 and 2014. We also discussed the isolation of the virus in Brazil in 2015 and its spread in the Americas, the microcephaly outbreak in Brazil and its association with Zika virus, and the current epidemiological panorama. We address the known clinical spectrum of Zika virus infection in the pediatric population, including manifestations of acute infection and congenital Zika syndrome, with emphasis on cranial, ophthalmic, and orthopedic abnormalities. CONCLUSION: While much has been learned about congenital Zika syndrome, the full spectrum of this infection is not yet known. This review is based on current, limited data about Zika vírus infection. As more information becomes available, we will have a more accurate picture of this new disease.

Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015.

In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August-October 2015 in eight of Brazil's 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear, and using insect repellents when outdoors. Pregnant and lactating women can use all U.S. Environmental Protection Agency (EPA)-registered insect repellents according to the product label.

Neurosurgical implications of Pott's puffy tumor in children and adolescents.

INTRODUCTION: Pott's puffy tumor (PPT) is rare and usually seen as a complication of frontal sinusitis resulting in subperiosteal abscess of the frontal bone with underlying osteomyelitis. PPT is potentially severe and can lead to life-threatening intracranial complications. PATIENTS AND METHODS: The authors present a series of six pediatric patients diagnosed with PPT and intracranial complications between 1999 and 2012. There were five boys and one girl, and the mean age at diagnosis was 11.8 years. All patients presented with frontal swelling, headache, and fever. Two patients had lowered level of consciousness and severe hemodynamic instability. RESULTS: All patients had epidural abscess, and one also presented subdural empyema. Five patients underwent drainage of all associated abscesses, bone resection, and sinusitis treatment. One was treated conservatively with broad-spectrum antibiotics, and no surgical intervention was required. All patients fully recovered their neurologic status, without further complications.

Longitudinal Follow-Up of Gross Motor Function in Children with Congenital Zika Virus Syndrome from a Cohort in Rio de Janeiro, Brazil.

Knowledge of how congenital Zika syndrome (CZS) impacts motor development of children longitudinally is important to guide management. The objective of the present study was to describe the evolution of gross motor function in children with CZS in a Rio de Janeiro hospital. In children with CZS without arthrogryposis or other congenital osteoarticular malformations who were followed in a prospective cohort study, motor performance was evaluated at two timepoints using the Gross Motor Function Classification System (GMFCS) and the Gross Motor Function Measurement test (GMFM-88). Among 74 children, at the baseline evaluation, the median age was 13 (8-24) months, and on follow-up, 28 (24-48) months. According to GMFCS at the second timepoint, 6 children were classified as mild, 11 as moderate, and 57 as severe. In the GMFM-88 assessment, children in the severe group had a median score of 10.05 in the baseline evaluation and a follow-up score of 12.40, the moderate group had median scores of 25.60 and 29.60, and the mild group had median scores of 82.60 and 91.00, respectively. Although a small developmental improvement was observed, the motor impairment of children was mainly consistent with severe cerebral palsy. Baseline motor function assessments were predictive of prognosis.

Anthropometric Parameters of Children with Congenital Zika Virus Exposure in the First Three Years of Life.

Little is known about the impact of congenital Zika virus (ZIKV) exposure on growth in the first years of life. In this prospective cohort study,201 ZIKV antenatally-exposed children were followed at a tertiary referral center in Rio de Janeiro, Brazil. Eighty-seven were classified as congenital Zika syndrome (CZS) patients and 114 as not congenital Zika syndrome (NCZS); growth parameters were described and compared between groups and with WHO standard growth curves. Thirty-four (39%) newborns with CZS and seven (6%) NCZS were small for gestational age (p < 0.001). NCZS mean weight measures ranged from −0.45 ± 0.1 to 0.27 ± 0.2 standard deviations (SD) from the WHO growth curve median during follow-up, versus −1.84 ± 0.2 to −2.15 ± 0.2 SD for the CZS group (p < 0.001). Length mean z-scores varied from −0.3 ± 0.1 at 1 month to 0.17 ± 0.2 SD between 31 and 36 months in the NCZS group, versus −2.3 ± 0.3 to −2.0 ± 0.17 SD in the CZS group (p < 0.001). Weight/height (W/H) and BMI z-scores reached -1.45 ± 0.2 SD in CZS patients between 31 and 36 months, versus 0.23 ± 0.2 SD in the NCZS group (p < 0.01). Between 25 and 36 months of age, more than 50% of the 70 evaluated CZS children were below weight and height limits; 36 (37.1%) were below the W/H cut-off. Gastrostomy was performed in 23 (26%) children with CZS. During the first three years of life, CZS patients had severe and early growth deficits, while growth of NCZS children was normal by WHO standards.

Early Predictors of Poor Neurologic Outcomes in a Prospective Cohort of Infants With Antenatal Exposure to Zika Virus.

BACKGROUND: Identify early predictors of poor neurodevelopment in infants with antenatal Zika virus (ZIKV) exposure. METHODS: Analysis of a prospective cohort of infants with antenatal ZIKV exposure confirmed by maternal or infant RT-PCR or IgM during the epidemic in Rio de Janeiro, Brazil. Clinical findings before 3 months of age were associated with Bayley-III Scales of Infant and Toddler Development conducted after 6 months of age. RESULTS: ZIKV exposure was confirmed in 219 cases; 162 infants were normocephalic, 53 were microcephalic, 4 had no head circumference recorded because of perinatal death/LTFU. Seven of the 112 normocephalic infants developed secondary microcephaly between 3 weeks and 8 months of age. Among the normocephalic at birth cohort, the mean HCZ among normal, at risk, and developmentally delayed children was significantly different (ANOVA, P = 0.02). In particular, the mean HCZ of the developmentally delayed group was significantly lower than that of the normal group (Tukey's test, P = 0.014). HCZ was more strongly associated with lower expressive language scores (P = 0.04) than receptive language scores (P = 0.06). The rate of auditory abnormalities differed among the normal, at risk, and developmentally delayed groups (Chi-squared test, P = 0.016), which was driven by the significant difference between the normal and at risk groups (post hoc test, P = 0.011, risk ratio 3.94). Auditory abnormalities were associated with both expressive and receptive language delays (P = 0.02 and P = 0.02, respectively). CONCLUSIONS: Clear predictors of neurodevelopment in normocephalic ZIKV-exposed children have not been previously identified. Our findings demonstrate that smaller HCZ and auditory abnormalities in these infants correlate with poor neurodevelopment as toddlers. Language delay is the most prominent developmental concern among these children, who will require frequent auditory and speech evaluations throughout childhood.

Characterizing Disabilities in Preschool Aged Children with Congenital Zika Virus Syndrome with the ICF Model.

Understanding functioning and disabilities in children with Congenital Zika Syndrome (CZS) is essential for health planning. We describe disabilities present in children with CZS followed in a reference hospital in Rio de Janeiro, Brazil, based on the biopsychosocial model of the International Classification of Functioning, Disability and Health (ICF). This was a cohort study of children >3 years of age with CZS. Disability was characterized through outcomes related to ICF components assessed via clinical and motor development evaluations. Among 50 children, with a median age of 40 months, 47 (94%) presented with severe impairment and 46 (92%) had microcephaly. Damage to the head and neck was found in most children, with abnormal central nervous system imaging universally present. Most children had cognitive impairment (92%), muscle tone problems (90%), and speech deficits (94%). We found movement limitations in all categories but more pervasively (80−94%), in postural transfers and displacements. The main environmental factors identified in the ICF model were the use of products or substances for personal consumption and access to health services. Children with CZS have extremely high rates of disability beyond aged 3 years, particularly regarding motor activity. ICF-based models can contribute to the assessment of health domains.

Acquired Hip Dysplasia in Children with Congenital Zika Virus Infection in the First Four Years of Life.

Acquired hip dysplasia has been described in children with cerebral palsy (CP); periodic surveillance is recommended in this population to prevent hip displacement and dislocation. Children with congenital zika syndrome (CZS) may present a spectrum of neurological impairments with changes in tonus, posture, and movement similar to children with CP. However, the relationship between CZS and hip dysplasia has not been characterized. In this prospective cohort study, we aimed to describe the occurrence of hip dysplasia in patients with CZS. Sixty-four children with CZS from 6 to 48 months of age were included and followed at a tertiary referral center in Rio de Janeiro, Brazil, with periodic radiologic and clinical hip assessments. Twenty-six (41%) patients were diagnosed with hip dysplasia during follow-up; mean age at diagnosis was 23 months. According to the Gross Motor Function Classification System (GMFCS), 58 (91%) patients had severe impairment (GMFCS IV and V) at the first evaluation. All patients with progression to hip dysplasia had microcephaly and were classified as GMFCS IV or V. Pain and functional limitation were reported by 22 (84%) caregivers of children with hip dysplasia. All patients were referred to specialized orthopedic care; eight (31%) underwent surgical treatment during follow-up. Our findings highlight the importance of implementing a hip surveillance program and improving access to orthopedic treatment for children with CZS in order to decrease the chances of dysplasia-related complications and improve quality of life.

Neurodevelopment of children exposed intra-uterus by Zika virus: A case series.

The main goal of this manuscript was to investigate the neurodevelopment of children exposed by Zika virus in the intrauterine period who are asymptomatic at birth. Newborns with documented Zika virus exposure during the intrauterine period who were asymptomatic at birth were followed in the first two years of life for neurodevelopment using Bayley III test. Children were classified as having normal or delayed neurodevelopment for age based on most recent Bayley III evaluation results. Eighty-four infants were included in the study. The first Bayley III evaluation was performed at a mean chronological age of 9.7±3.1 month; 13 children (15%) had a delay in one of the three domains, distributed as follow: 10 (12%) in the language domain and 3 (3.5%) in the motor domain. The most recent Bayley III evaluation was performed at a mean age 15.3±3.1 months; 42 children (50%) had a delay in one of the three domains: 4 (5%) in cognition, 31 (37%) in language, and 20 (24%) in motor performance. There were no statistical differences in Gender, Gestational Age, Birth Weight and Head Circurference at birth between children with normal and delayed neurodevelopment for age. A very high proportion of children exposed ZIKV during pregnancy who were asymptomatic at birth demonstrated a delay in neurodevelopment, mainly in the language domain, the first two years of life.

24-hour Holter findings in infants with in-utero exposure to the Zika virus: a series of cases.

Severe neurological problems and other special manifestations such as high prevalence of structural cardiac changes has been described in infants vertically exposed to the Zika virus (ZIKV) and has been called congenital Zika virus syndrome (CZS). Previous studies have shown that the 24-hour Holter heart rate variability (HRV) analysis allows the prediction of worse outcomes in infants with neurological impairment and higher risk of sudden infant death syndrome (SIDS), hypertension, diabetes mellitus and other cardiovascular diseases. This study describes the 24-hour Holter findings of infants with confirmed vertical exposure to the ZIKV by positive polymerase chain reaction (PCR) assays in the mother's blood during pregnancy and/or in the urine or cerebrospinal fluid of the newborn. Data analysis was descriptive and included two subgroups according to the presence of fetal distress, positive PCR to ZIKV in the newborn, CZS and severe microcephaly. Heart rate, pauses, arrhythmias, ST segment and QT interval analyses and HRV evaluation through R-R, SDNN, pNN50 and rMMSD were described. The Mann-Whitney test was performed to assess differences between the two subgroups. The sample consisted of 15 infants with a mean age of 16 months, nine of whom were male. No arrhythmias or QT interval changes were observed. The comparison of HRV through the Mann-Whitney test showed a significant difference between patients with and without CZS, with and without severe microcephaly, with lower HRV in the groups with severe microcephaly and CZS. The study suggests that there is an increased risk of SIDS and cardiovascular diseases in this group of patients.

Association Between Antenatal Exposure to Zika Virus and Anatomical and Neurodevelopmental Abnormalities in Children.

Importance: Zika virus (ZIKV) is a mosquito-borne flavivirus recognized as teratogenic since the 2015 to 2016 epidemic. Antenatal ZIKV exposure causes brain anomalies, yet the full spectrum has not been delineated. Objective: To characterize the clinical features of ZIKV infection at a pediatric referral center in Rio de Janeiro, Brazil, among children with antenatal ZIKV exposure. Design, Setting, and Participants: Retrospective cohort study conducted from May to July 2019 of a prospective cohort of 296 infants with antenatal ZIKV exposure followed up since December 2015 at a tertiary maternity-pediatric hospital. Exposures: Zika virus infection during pregnancy. Main Outcomes and Measures: Characterization of clinical features with anthropometric, neurologic, cardiologic, ophthalmologic, audiometric, and neuroimaging evaluations in infancy and neurodevelopmental assessments (Bayley Scales of Infant and Toddler Development, Third Edition) from 6 to 42 months of age, stratified by head circumference at birth (head circumference within the reference range, or normocephaly [NC] vs microcephaly [MC]). Results: Antenatal exposure to ZIKV was confirmed for 219 of 296 children (74.0%) referred to Instituto Fernandes Figueira with suspected ZIKV infection through positive maternal or neonatal polymerase chain reaction analysis or IgM serology results. Of these children, 110 (50.2%) were boys, ages ranged from 0 to 4 years, and 53 (24.2%) had congenital microcephaly. The anomalies observed in ZIKV-exposed children with MC or NC were failure to thrive (MC: 38 of 53 [71.7%]; NC: 73 of 143 [51.0%]), cardiac malformations (MC: 19 of 46 [41.3%]; NC: 20 of 100 [20.0%]), excess nuchal skin (MC: 16 of 22 [72.7%]; NC: 35 of 93 [37.6%]), auditory abnormalities (MC: 13 of 50 [26.0%]; NC: 14 of 141 [9.9%]), and eye abnormalities (MC: 42 of 53 [79.2%]; NC: 28 of 158 [17.7%]). Although they experienced fewer neurologic abnormalities than children born with MC, those with NC also had frequent neurologic abnormalities (109 of 160 [68.1%]), including hyperreflexia (36 of 136 [26.5%]), abnormal tone (53 of 137 [38.7%]), congenital neuromotor signs (39 of 93 [41.9%]), feeding difficulties (15 of 143 [10.5%]), and abnormal brain imaging results (44 of 150 [29.3%]). Among 112 children with NC with Bayley-III evaluations, 72 (64.3%) had average or above-average scores; 30 (26.8%) scored 1 SD below average in at least 1 domain; and 10 (8.9%) scored 2 SD below average in at least 1 domain. Among 112 children with NC, a smaller head circumference at birth was significantly associated with subsequent below-average cognitive scores (U = 499.5; z = -2.833; P = .004) and language scores (U = 235.5; z = -2.491; P = .01). Conclusions and Relevance: Children without MC who were exposed to ZIKV in utero had a high frequency of anatomical and neurodevelopmental abnormalities. The head circumference at birth for children with NC was associated with neurocognitive development. Recognition of the wide spectrum of clinical phenotypes is critical to ensure early referral to rehabilitative interventions.

Serological biomarkers for monitoring response to treatment of pulmonary and extrapulmonary tuberculosis in children and adolescents.

Key measures to halt the spread of tuberculosis (TB) include early diagnosis, effective treatment, and monitoring disease management. We sought to evaluate the use of serum immunoglobulin levels against antigens present in cell envelope of Mycobacterium tuberculosis to monitor TB treatment response in children and adolescents with pulmonary (PTB) or extrapulmonary TB (EPTB). Blood samples were collected prior to and one, two, and six months following treatment initiation. Serum immunoglobulin levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein were measured by ELISA. Serum from 53 TB patients and 12 healthy participants were analyzed. After six months of successful treatment, there was a significant decrease (p < 0.0001) in IgM levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein and IgG levels against Mce1A protein when compared to baseline immunoglobulin levels. There was no significant variation in antibody levels during follow-up between participants with PTB and EPTB, confirmed and unconfirmed TB diagnosis, and HIV infection status. Antibody levels in control participants without TB did not decrease during follow-up. These results suggest that immunoglobulin responses to mycobacterial cell wall products may be a useful tool to monitor treatment response in children and adolescents with PTB or EPTB.

Zika virus vertical transmission in children with confirmed antenatal exposure.

We report Zika virus (ZIKV) vertical transmission in 130 infants born to PCR+ mothers at the time of the Rio de Janeiro epidemic of 2015-2016. Serum and urine collected from birth through the first year of life were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM Zika MAC-ELISA. Four hundred and seven specimens are evaluated; 161 sera tested by PCR and IgM assays, 85 urines by PCR. Sixty-five percent of children (N = 84) are positive in at least one assay. Of 94 children tested within 3 months of age, 70% are positive. Positivity declines to 33% after 3 months. Five children are PCR+ beyond 200 days of life. Concordance between IgM and PCR results is 52%, sensitivity 65%, specificity 40% (positive PCR results as gold standard). IgM and serum PCR are 61% concordant; serum and urine PCR 55%. Most children (65%) are clinically normal. Equal numbers of children with abnormal findings (29 of 45, 64%) and normal findings (55 of 85, 65%) have positive results, p = 0.98. Earlier maternal trimester of infection is associated with positive results (p = 0.04) but not clinical disease (p = 0.98). ZIKV vertical transmission is frequent but laboratory confirmed infection is not necessarily associated with infant abnormalities.