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Abstract Objectives: To ascertain total body water in small for gestational age (SGA) and appropriate for gestational age (AGA) newborns. Methods: SGA and AGA babies were matched by gestational age and studied from birth to term age. Criteria for exclusions were genetic syndromes, malformations, and congenital infections. Bioelectrical impedance was performed at two days of life (term infants), or at seven days of life and term age (preterm infants). Weight and length were measured by trained interviewers, and Z-score, weight/length ratio and Rohrer ponderal index was calculated. Results: Of the 54 infants evaluated, 28 were SGA (17 preterm) and 26 were AGA (15 preterm). Total body water was greater in SGA preterm babies at seven days of age (P=0.058) and at term age (P<0.0001). Weight/length ratio and Rohrer ponderal index increased towards term. Weight Z-score and anthropometric measures at term were significantly smaller in SGA babies. Being SGA and variation in Rohrer ponderal index influenced the variations in total body water. Conclusions: SGA babies had greater total body water, and both groups presented insufficient increase in body solid mass, stressing the importance of nutritional support during neonatal care. [ABSTRACT FROM AUTHOR]

Objective: To compare O(2) consumption, CO(2) production, respiratory quotient and resting metabolic rate in premature neonates measured for 5 and 10 min steady-state periods and 15 and 20 min non-steady-state periods versus a 2-h measurement period. Methods: A prospective study with neonates evaluated by indirect calorimetry. The measurements from the 5, 10, 15, and 20 min periods were taken based on the printout data from the IC monitor at an interval of 1 h before the beginning feeding and were contained in the 2-h measurement. The 5- and 10-min measurements followed the steady-state criterion. Results: We evaluated 35 premature neonates appropriate for gestational age (born at 28-34 weeks' gestation). Mean age was 20 days +/-9 (median 14 days) and mean weight was 1530+/-270 g (median 1510 g). There was no statistically significant difference between mean VO(2), VCO(2), respiratory quotient and energy expenditure at 5, 10, 15, and 20 min and 2 h. Conclusions: The 5 and 10 min steady-state measurements or a measurement of more than 15 min without reaching steady state produce results similar to those of 2 h measurements. [ABSTRACT FROM AUTHOR]

The study is intended to illustrate that the nursing phenomenon, Violence, exists as a phenomenon of the aggregate and should thus be classified, under the higher level phenomenon, Community, in the International Classification for Nursing Practice (ICNP), published by the International Council of Nurses. This proposition was confirmed during a meeting of an international team of psychiatric nurses to plan reality-based postgraduate modules for the nine countries they represented. Substantiating data, based on the team's module, Violence, clinical investigation and a review of the literature, evolved from a classroom project in north-east Brazil. The Master's Degree nursing students conducted observations and interviews based on identified factors of the phenomenon on children in two municipal day-care centers in targeted neighborhoods in Joao Pessoa, Paraiba, Brazil. Data were gleaned from observations and verbalizations regarding their individual drawings depicting sadness and happiness, from school records and observations of these children by their teachers. The data, evolving from the time-limited classroom project, are too sparse to be considered valid, but pave the road for further studies. Professional and lay-literature substantiates the occurrence of violence in the Brazilian society. [ABSTRACT FROM AUTHOR]

A eletrocardiografia pode ser usada para quantificar o treinamento e o desempenho atlético. Pode ainda avaliar a função cardíaca sob efeito do exercício identificando a influência de anomalias cardíacas, assim como os efeitos deletérios do esforço frente à função cardíaca. Considerando a complexidade do esforço físico inerente a cavalos em competições de polo, juntamente com a carência de relatos na literatura sobre a demanda cardíaca resultante. O objetivo deste estudo foi o de identificar e avaliar eletrocardiograficamente os efeitos cardíacos do exercício de polo em equinos de forma a subsidiar dados para a compreensão da demanda fisiológica cardíaca desta modalidade. Foram avaliados 27 equinos praticante de polo em repouso e entre cinco e dez minutos após o exercício. Os resultados obtidos demonstraram que as alterações observadas na duração e amplitude da onda P e duração do intervalo PR e QT foram consideradas fisiológicas em resposta ao aumento da frequência cardíaca. A onda P difásica encontrada em repouso representou hipertrofia atrial e quando bífida representou diferentes pontos de ativação do nó sinoatrial. Como esperado o complexo QRS não sofreu alterações consideráveis entre os dois momentos. O supradesnível do segmento ST e as variações da onda T observadas após o exercício poderiam representar efeito adverso ao miocárdio, entretanto estudos analisando múltiplos fatores são necessários para confirmar esta associação e definir sua real causa. O aumento do QTc sugeriu fadiga miocárdica leve representando alta demanda cardíaca para esta modalidade. O escore cardíaco demonstrou que estes animais estavam dentro do padrão de adaptação cardíaca para um cavalo atleta. A rápida recuperação cardíaca demonstrou bom condicionamento atlético. O marca-passo atrial mutável foi um achado normal encontrado nos equinos de polo. Foi observada baixa incidência de alterações no ritmo cardíaco.

Objective To measure the irradiance in humidified incubator under three different overhead phototherapy devices. Design/methods The effective irradiance of three phototherapy devices was assessed by taking a series of irradiance measurements in the illuminated field. Measurements were made with a fixed bandwidth broadband radiometer (380-530 nm). The distance between the light source and the radiometer was 35 cm for the daylight fluorescent lamp, 40 cm for the light emitting diode (LED) and 50 cm for the halogen phototherapy. A double-wall incubator was kept at 36°C and set at three different levels of humidity (60-70%, 80% and equal or above 90%). Results The irradiance under the overhead daylight fluorescent lamp phototherapy did not change with the increasing humidity. However, above 90% humidity, when water vapour inside the incubator was so saturated to the point of totally condensing in the incubator walls, the measured irradiance decreased 15% of the initial values with the blue LED phototherapy and 45% with the halogen spotlight phototherapy. Conclusions Highly humidified incubators are frequently used to treat very low birthweight infants. Health professionals should be aware that mist and water condensation inside an incubator may significantly reduce the efficacy of treatment. [ABSTRACT FROM AUTHOR]

Background: Congenital Zika virus (ZIKV) infection leads to severe newborn abnormalities, but its long-term impact on childhood immunity is not well understood. This study aims to investigate the serum proteomics in children exposed to ZIKV during pregnancy to understand potential immunological consequences during early childhood., Methods: The study included ZIKV-exposed infants (ZEI) at birth (n = 42) and children exposed to ZIKV (ZEC) at two years of age (n = 20) exposed to ZIKV during pregnancy, as well as healthy controls. Serum proteomic analysis was performed on these groups to assess inflammation and immune profiles. Additionally, antibody titres against two common childhood vaccines, DTaP and MMR, were measured in healthy controls (n = 50) and ZEC (n = 92) to evaluate vaccine-induced immunity., Findings: Results showed elevated inflammation in ZEI with birth abnormalities. Among ZEC, despite most having normal clinical outcomes at two years, their serum proteomics indicated a bias towards Th1-mediated immune responses. Notably, ZEC displayed reduced anti-Diphtheria toxin and anti-Clostridium tetani IgG levels against DTaP and MMR vaccines. They also exhibited lower antibody titres particularly against Th2-biased DTaP vaccines, but not Th1-biased MMR vaccines., Interpretation: In conclusion, the study highlights the long-term immunological consequences of congenital ZIKV exposure. Heightened inflammation was observed in ZEI with abnormalities at birth, while ZEC maintained a chronic Th1-biased immune profile. The impaired response to Th2-biased vaccines raises concerns about lasting effects of ZIKV exposure on immune responses. Consequently, there is a need for continued longitudinal clinical monitoring to identify potential immune-related complications arising from prenatal exposure to ZIKV., Funding: This work was partially funded by the National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Dental and Craniofacial Research (NIDCR)., Competing Interests: Declaration of interests MEM has received speaker fees from Baxter. The other authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the association between sociodemographic and perinatal factors and hospital practices to encourage exclusive breastfeeding in near miss neonates in maternity hospitals., Methods: This is a prospective cohort of live births from the survey "To be born in Brazil" conducted between 2011 and 2012. The weighted number of newborns who met the neonatal near miss criteria was 832. Exclusive breastfeeding at hospital discharge and 45 days after delivery were dependent variables of the study. The sociodemographic and perinatal factors of the puerperal women and hospital practices to encourage breastfeeding were independent variables. The data were analyzed with Poisson regression and set with p value<0.05. Is exclusive breastfeeding in neonatal near misses associated with factors related to sociodemographic conditions, maternal characteristics and the organization of health services?, Results: Data from 498 women and their children were analyzed. Mothers with incomplete primary education were more likely (36%) to have exclusive breastfeeding (RR: 1.36; 95% CI: 1.06-1.74) at discharge. Women who did not offer the breast to the newborn in the joint accommodation (65%) were less likely to be breastfeeding exclusively (RR: 0.65; 95% CI: 0.56-0.75) at discharge. Variables that increased the probability of exclusive breastfeeding after 45 days of delivery were primiparity (RR: 1.36; 95% CI: 1.08-1.69) and having the newborn in the delivery room (RR: 1.90; 95% CI: 1.12-3.24)., Conclusion: Exclusive breastfeeding in neonatal near misses was associated with maternal characteristics and important hospital practices, such as being breastfed in the joint accommodation and the newborn being in the mother's lap in the delivery room., Competing Interests: Conflicts to interest: none to declare.

It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < - 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5-30 months of age and 128 control children between 6-38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1-6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up., (© 2024. The Author(s).)

Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4 . Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1 , 3 , and 4 , whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies., Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks., Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association., Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%., Competing Interests: Declaration of interests We declare no competing interests.

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.

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.., Competing Interests: Dr. Gaw reports grants from National Institutes of Health, other from Burroughs Wellcome Fund for the Reproductive Scientist Development Program, other from Queenan Fellowship from the Foundation for the Society of Maternal-Fetal Medicine, other from UCSF National Center of Excellence in Women's Health, grants from Departamento de Ciência e Tecnologia (DECIT) do Ministério da Saúde do Brasil, grants from Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, grants from Wellcome Trust, other from United Kingdom's Department for International Development, grants from European Union's Horizon 2020 Research and Innovation Program, outside the submitted work., (Thieme. All rights reserved.)

Background: The 2015-16 Zika epidemic resulted in thousands of children born with congenital Zika syndrome (CZS). In Brazil, gaps in the health system often caused parents to be left with insufficient information and support. Consequently, we developed and piloted Juntos - a participatory support programme which aims to improve knowledge, capacities and build support networks for caregivers of children with CZS.   Methods: Six caregiver groups received the programme between August 2017 and June 2018: three in Rio de Janeiro and three in Bahia. We assessed the feasibility of Juntos against six of the eight areas of a feasibility framework described by Bowen et al. to consider whether Juntos 'could work'. These areas were: acceptability, demand, implementation, practicality, adaptation and limited efficacy. We used mixed methods including: 1) baseline and end-line questionnaires completed by all group participants; 2) in-depth interviews with 18 participants, seven facilitators and three key stakeholders; 3) participant focus group discussions after each session; 4) researchers session observation; and 5) recording programme costs.  Results: 37/48 (77%) enrolled families completed both questionnaires. Acceptability and demand were noted as high, based on participant responses to interview questions, focus group feedback and satisfaction scores. Potential for implementation and practicality were also demonstrated through interviews with facilitators and key stakeholders and analysis of project documents. Two groups included caregivers of children with non-Zika related developmental disabilities, showing potential for adaptability. Self-reported quality of life scores increased in caregivers between baseline and end-line, as did the dimensions of family relationships and daily activities in the Pediatric Quality of Life Inventory (PEDS QL) Family Impact Module, showing limited efficacy.   Conclusions: The programme showed feasibility according to Bowen's framework. However, further research of scale up, particularly in the areas of integration, expansion and limited efficacy are needed to ascertain if the programme is effective., Competing Interests: Competing interests: One of the researchers (AD) joined the Pan American Health Organisation (PAHO) during the research period. Work on the research study was undertaken outside and separate to his PAHO duties., (Copyright: © 2022 Duttine A et al.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2021. The Author(s).)

While pregnancy increases the risk for severe COVID-19, the clinical and immunological implications of COVID-19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID-19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1,400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation. Pregnant women with severe COVID-19 show increased inflammation and unique IFN-λ antiviral signaling, with elevated levels of IFNL1 and IFNLR1. Furthermore, SARS-CoV-2 infection re-shapes maternal immunity at delivery, altering the expression of pregnancy complication-associated cytokines, inducing MMP7, MDK, and ESM1 and reducing BGN and CD209. Finally, COVID-19-exposed infants exhibit induction of T cell-associated cytokines (IL33, NFATC3, and CCL21), while some undergo IL-1β/IL-18/CASP1 axis-driven neonatal respiratory distress despite birth at term. Our findings demonstrate COVID-19-induced immune rewiring in both mothers and neonates, warranting long-term clinical follow-up to mitigate potential health risks., Competing Interests: J.U.J. is a scientific adviser to Vaccine Stabilization, a California corporation., (© 2021 The Author(s).)

Purpose: To analyze the spectrum of ophthalmologic manifestations in a large sample of children with congenital Zika syndrome (CZS) in Brazil., Methods: The medical records of infants born in the states of Pernambuco, Bahia, and Rio de Janeiro, Brazil, between December 2015 and December 2016 with clinical manifestations of CZS and positive reverse transcription polymerase-chain-reaction (RT-PCR) and/or serology for the Zika virus were reviewed retrospectively. Data were collected from the record of the first ophthalmological assessment, performed on admission. Children with other congenital infectious diseases, genetic conditions, and incomplete medical records were excluded., Results: A total of 469 infants (242 female [51.6%]) were included. Mean age at examination was 5.0 ± 7.1 months (range, 0.0-36.0 months). Of the 469 infants, 197 (42.0%) were from Rio de Janeiro, 144 (30.7%) from Pernambuco, and 128 (27.3%) from Bahia States. Microcephaly at birth was detected in 214 (45.6%) children; 62 cases (29.0%) were severe. Pernambuco had significantly more children born with microcephaly compared with Bahia and Rio de Janeiro (P < 0.001). Ocular manifestations were found in 269 of 938 eyes (28.7%; 148/469 children [31.6%]). The main ocular alterations were optic nerve pallor in 122 of 938 eyes (13.0%), focal pigment mottling in 112 eyes (11.9%), and chorioretinal scars in 101 eyes (10.8%). A higher prevalence of ocular manifestations was seen in Pernambuco (P < 0.001). No microcephaly was observed in 252 of 466 children (54.1%); of these, 19 children (7.5%) had funduscopic findings., Conclusions: One-third of children with CZS had ocular manifestations. Children from Pernambuco were more affected. Ocular abnormalities were found in 7.5% of children without microcephaly., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background: Lateral canthotomy is a vision-saving procedure. However, the low incidence of orbital compartment syndrome and the expense of simulators to practice this procedure can lead to low confidence and delays in the performance of the procedure by emergency physicians., Discussion: We used a simple, inexpensive, easily assembled eye model for lateral canthotomy education at a residency program and a national conference obtaining feedback from simulation participants. Residents rated procedure laboratories that included the lateral canthotomy model as 4.9 to 5 (on a 5-point Likert scale, with 5 being the best score). National conference participants rated the model a 9 as a useful training model for practitioners on a 10-point Likert scale., Conclusion: This simple task trainer is practical, inexpensive, quickly assembled, and useful as a tool for practicing emergency medicine providers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: To evaluate the potential factors associated with the nutritional composition of human milk of puerperal women., Methods: cross-sectional study, conducted between March 2016 and August 2017, with 107 women, selected in a Tertiary Health Care Tertiary Health Facility of the Unified Health System (SUS) in the Municipality of Rio de Janeiro. Data were collected two months after delivery. The dependent variable of the study was the nutritional composition of human milk. We divided the independent variables into hierarchical levels: distal (age, schooling, parity and pregestational nutritional status), intermediate (number of prenatal visits and gestational weight gain) and proximal (alcohol consumption, smoking, diabetes mellitus and hypertension). For data analysis, we applied the multiple linear regression, centered on the hierarchical model. Only the variables associated with the nutritional composition of breast milk remained in the final model at a 5% level of significance., Results: The nutritional composition of human milk yielded by women with pregestational overweight, smokers and hypertensive had higher amounts of lipids and energy. Conversely, women with gestational weight gain below the recommended had lower amounts of these components., Conclusion: The evaluation of factors associated with the nutritional composition of human milk is extremely important to assist post-partum care practices. In this study, we observed that lipid and energy contents were associated to pregestational nutritional status, gestational weight gain, smoking and hypertension.

The Zika virus (ZIKV) epidemic in Brazil occurred in regions where dengue viruses (DENV) are historically endemic. We investigated the differences in adverse pregnancy/infant outcomes in two cohorts comprising 114 pregnant women with PCR-confirmed ZIKV infection in Rio de Janeiro, Southeastern Brazil ( n = 50) and Manaus, in the north region of the country ( n = 64). Prior exposure to DENV was evaluated through plaque reduction neutralizing antibody assays (PRNT 80) and DENV IgG serologies. Potential associations between pregnancy outcomes and Zika attack rates in the two cities were explored. Overall, 31 women (27%) had adverse pregnancy/infant outcomes, 27 in Rio (54%) and 4 in Manaus (6%), p < 0.001. This included 4 pregnancy losses (13%) and 27 infants with abnormalities at birth (24%). A total of 93 women (82%) had evidence of prior DENV exposure, 45 in Rio (90%) and 48 in Manaus (75%). Zika attack rates differed; the rate in Rio was 10.28 cases/10,000 and in Manaus, 0.6 cases/10,000, p < 0.001. Only Zika attack rates (Odds Ratio: 17.6, 95% Confidence Interval 5.6-55.9, p < 0.001) and infection in the first trimester of pregnancy (OR: 4.26, 95% CI 1.4-12.9, p = 0.011) were associated with adverse pregnancy and infant outcomes. Pre-existing immunity to DENV was not associated with outcomes (normal or abnormal) in patients with ZIKV infection 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.

Intrauterine transmission of the Chikungunya virus (CHIKV) during early pregnancy has rarely been reported, although vertical transmission has been observed in newborns. Here, we report four cases of spontaneous abortion in women who became infected with CHIKV between the 11th and 17th weeks of pregnancy. Laboratorial confirmation of the infection was conducted by RT-PCR on a urine sample for one case, and the other three were by detection of IgM anti-CHIKV antibodies. Hematoxylin and eosin (H&E) staining and an electron microscopy assay allowed us to find histopathological, such as inflammatory infiltrate in the decidua and chorionic villi, as well as areas of calcification, edema and the deposition of fibrinoid material, and ultrastructural changes, such as mitochondria with fewer cristae and ruptured membranes, endoplasmic reticulum with dilated cisterns, dispersed chromatin in the nuclei and the presence of an apoptotic body in case 1. In addition, by immunohistochemistry (IHC), we found a positivity for the anti-CHIKV antibody in cells of the endometrial glands, decidual cells, syncytiotrophoblasts, cytotrophoblasts, Hofbauer cells and decidual macrophages. Electron microscopy also helped in identifying virus-like particles in the aborted material with a diameter of 40-50 nm, which was consistent with the size of CHIKV particles in the literature. Our findings in this study suggest early maternal fetal transmission, adding more evidence on the role of CHIKV in fetal death.

This paper aims to compare best practices for healthy newborns in public and mixed hospitals affiliated with SUS, according to type of birth, between "Nascer no Brasil/2011" (NB - Birth in Brazil) and in the last assessment cycle of Rede Cegonha, here called "Avaliação da Rede Cegonha/2017" (ARC - Stork Network Assessment). NB included a sample with national representativeness of 266 hospitals, and ARC was conducted in 606 maternity hospitals included in the Rede Cegonha strategy, totaling 15,994 and 8,047 pairs of healthy mothers and newborns, respectively.Between the two studies, NB-2011 and ARC-2017, although the proportion of cesarean sections remained around 44%, the prevalence of skin-to-skin contact with newborns, breastfeeding in the delivery room and breastfeeding in the first 24h of life increased by 140%, 82% and 6%, respectively. The proportion of upper airway aspiration of newborns dropped 65%. The results indicate that the use of evidence-based guidelines for the care of healthy newborns has increased in clinical practice, considering the six-year period between the compared studies. Despite the progress, important challenges remain to ensure best practices for all women and newborns, especially in relation to cesarean births.

This study aims to evaluate the impact of excess body weight, diabetes mellitus, and hypertension on the nutritional composition of human milk. This cohort study was conducted at a tertiary public health unit in the city of Rio de Janeiro from March 2016 to February 2018. The data were collected in two stages (96 hours and one month after delivery). The macronutrients (carbohydrate, protein, lipid) and total energy were determined using the MIRIS ® equipment. The level of significance was 5%. Higher protein content was observed in the nutritional composition of colostrum in women with diabetes mellitus. A higher protein and energy content was observed in the milk of mothers with excessive body weight. The energy content was higher in the milk of mothers with excessive body weight. Increased protein content in the human milk of women with excessive body weight or diabetes.

Background: Twin pregnancies account for 0.5-2.0% of all gestations worldwide. They have a negative impact on perinatal health indicators, mainly owing to the increased risk for preterm birth. However, population-based data from low/middle income countries are limited. The current paper aims to understand the health risks of twins, compared to singletons, amongst late preterms and early terms., Methods: Data is from "Birth in Brazil", a national inquiry into childbirth care conducted in 2011/2012 in 266 maternity hospitals. We included women with a live birth or a stillborn, and excluded births of triplets or more, totalling 23,746 singletons and 554 twins. We used multiple logistic regressions and adjusted for potential confounders., Results: Twins accounted for 1.2% of gestations and 2.3% of newborns. They had higher prevalence of low birth weight and intrauterine growth restriction, when compared to singletons, in all gestational age groups, except in the very premature ones (<34 weeks). Amongst late preterm's, twins had higher odds of jaundice (OR 2.7, 95% CI 1.8-4.2) and antibiotic use (OR 1.8, 95% CI 1.1-3.2). Amongst early-terms, twins had higher odds of oxygen therapy (OR 2.7, 95% CI 1.3-5.9), admission to neonatal intensive care unit (OR 3.1, 95% CI 1.5-6.5), transient tachypnoea (OR 3.7, 95% CI 1.5-9.2), jaundice (OR 2.8, 95% CI 1.3-5.9) and antibiotic use (OR 2.2, 95% CI 1.14.9). In relation to birth order, the second-born infant had an elevated likelihood of jaundice, antibiotic use and oxygen therapy, than the first-born infant., Conclusion: Although strongly mediated by gestational age, an independent risk remains for twins for most neonatal morbidities, when compared to singletons. These disadvantages seem to be more prominent in early-term newborns than in the late preterm ones., Competing Interests: The authors have declared that no competing interests exist.

Objective: To analyze adverse fetal and neonatal outcomes of Zika virus infection by the timing of infection during pregnancy. Method: Cohort study of 190 pregnancies with 193 offspring with a positive RT-PCR test for Zika virus (March/2016 to April/2017)., Results: Death or defects related to congenital Zika virus infection were identified in 37.3% of fetuses and newborns, and microcephaly in 21.4% of the newborns. The proportion of small for gestational age newborns was 21.9%. Maternal symptoms in the first trimester were significantly associated with the birth of newborns with microcephaly/cerebral atrophy, small for gestational age and with the deaths (one abortion, one stillbirth and the two neonatal deaths). Maternal infection during the second trimester was further associated with asymptomatic newborns at birth. The study showed that 58.5% of the offspring with microcephaly and / or cortical atrophy were small for gestational age, with an evident decrease in symptomatic offspring without microcephaly, 24.1%, and with only 9.1% in the asymptomatic group., Conclusion: This study showed that the earlier the symptoms appear during gestation, the more severe the endpoints. We found a higher percentage of small for gestational age newborns exposed to Zika virus early in gestation. We also found a group of apparently asymptomatic newborns with proven Zika infection, which highlights the importance of follow up studies in this population., Competing Interests: The authors have declared that no competing interests exist.

Background: The 2015-2016 Zika virus outbreak in Brazil was unprecedented and resulted in the birth of more than 3,000 children with congenital Zika syndrome (CZS). These children experience multiple complex health conditions and have limited services to support them and their family's needs., Program Development and Piloting: An existing family support program for children with cerebral palsy (Getting to Know Cerebral Palsy) was adapted to the Zika context in Brazil through expert consultation. The program was pilot tested at 2 sites among 6 groups of caregivers (total of 48 families) from August 2017 to June 2018. Group observation and focus group discussions with facilitators and participants at the end of each session informed fast-track learning, which was used to tailor the program for future groups. Fast-track learning-adjusting the intervention in real time based on gathered feedback-was found to be a helpful process to inform and hone the program from its initial concept., Program Description: The intervention, Juntos, is a facilitated participatory group program for caregivers of children who have CZS. The group sessions are cofacilitated by a parent of a child who has CZS and an allied health professional. The group meets for 10 sessions that last 4 hours. Each session includes an icebreaker, activities, and group discussions. Content covers practical information on caring for a child with a developmental disability including that caused by Zika. Psychosocial support forms an important component, and families are guided from the first week to define and develop their own communities of support. Six pilot groups were successfully run in Rio de Janeiro and Greater Salvador, Bahia. The groups gave positive feedback on acceptability and demand., Conclusions: The program has the potential to be an important tool for community health and social support services in South America in response to Zika. The program can also be applied to children with neurodevelopmental disabilities other than those caused by the Zika virus, which could be important in ensuring families of children with CZS are less isolated., (© Duttine et al.)

Introduction: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean., Methods and Analysis: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach., Ethics and Dissemination: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form. The following authors report grants from the European Commission (AEA, EBB, NA, DB, TJ, KDR, CT, CDCC, AS-A, JGM, CG, Xd-L, AW-S); EBB reports funding from by Wellcome Trust & the UK’s Department for International Development; MT reports grants from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil and from Fundacao de Amparo a Pesquisa do EStado de MInas Gerais (FAPEMIG, Brazil), during the conduct of the study; MK has a patent on zika diagnostics pending., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Increased rates of Zika virus have been identified in economically deprived areas in Brazil at the population level; yet, the implications of the interaction between socioeconomic position and prenatal Zika virus exposure on adverse neurodevelopmental outcomes remains insufficiently evaluated at the individual level. Using data collected between September 2015 and September 2019 from 163 children with qRT-PCR and/or IgM-confirmed prenatal exposure to Zika virus participating in a prospective cohort study in Rio de Janeiro, Brazil (NCT03255369), this study evaluated the relationships of socioeconomic indicators with microcephaly at birth and Bayley-III neurodevelopmental scores during the early life course. Adjusted logistic regression models indicated increased odds of microcephaly in children born to families with lower household income (OR, 95% CI: 3.85, 1.43 to 10.37) and higher household crowding (OR, 95% CI: 1.83, 1.16 to 2.91), while maternal secondary and higher education appeared to have a protective effect for microcephaly compared to primary education (OR, 95% CI: 0.33, 0.11 to 0.98 and 0.10, 0.03 to 0.36, respectively). Consistent with these findings, adjusted linear regression models indicated lower composite language (-10.78, 95% CI: -19.87 to -1.69), motor (-10.45, 95% CI: -19.22 to -1.69), and cognitive (-17.20, 95% CI: -26.13 to -8.28) scores in children whose families participated in the Bolsa Família social protection programme. As such, the results from this investigation further emphasise the detrimental effects of childhood disadvantage on human health and development by providing novel evidence on the link between individual level socioeconomic indicators and microcephaly and delayed early life neurodevelopment following prenatal Zika virus exposure.

Background: The association between gestational weight gain and neonatal body composition has been inconsistent, exposing the need for further research. The aim of this study was to evaluate whether gestational weight gain influences the body composition of full-term newborns and infants up to 4 months old., Methods: A cohort study was performed with 124 participants divided into categories of gestational weight gain according to the 2009 Institute of Medicine guidelines. The anthropometric and body composition data of newborns and infants acquired using air displacement plethysmography (PeaPod®) were collected at 96 h, 1 month, 2 months and 4 months of life. In the statistical analysis, the chi-square test was used to analyze categorical variables, and ANOVA was used to analyze numerical variables. Univariate analysis was performed, and the absolute and relative frequencies of the categorical variables, as well as mean and standard deviation of the numerical variables, were obtained. Bivariate analysis was performed for the categories of gestational weight gain and gestational and neonatal characteristics. When adjustments to gestational hypertension, gestational diabetes, and pregestational body mass index (BMI) were analyzed by linear regression, gestational weight gain remained a significant variable for newborn percent fat mass. For all analyses, a significance level of 5% was adopted., Results: Gestational weight gain was adequate in 33.8% of the participants, excessive in 41.1% and insufficient in 25%. Women with excessive weight gain had higher pregestational BMIs and a higher incidence of gestational hypertension. Their newborns had a higher body mass, body fat mass in grams and percent fat mass than the infants born to mothers with adequate or insufficient gestational weight gain. No significant differences were observed in body composition at 1, 2 and 4 months of life during infant follow-up., Conclusion: Excessive gestational weight gain may alter the body composition of newborns at birth. Further studies are required to better evaluate infant follow-up., Trial Registration: Clinical Trial Registry: NCT00875251 on April 3, 2009.

Zika virus (ZIKV) has evolved into a global health threat because of its causal link to congenital Zika syndrome. ZIKV infection of pregnant women may cause a spectrum of abnormalities in children. In the studies in Brazil, a large cohort of children with perinatal exposure to ZIKV is followed, and a spectrum of neurodevelopmental abnormalities is identified. In parallel, it is demonstrated that infection of the mouse neonatal brain by a contemporary ZIKV strain instead of an Asian ancestral strain can cause microcephaly and various abnormal neurological functions. These include defects in social interaction and depression, impaired learning and memory, in addition to severe motor defects, which are present in adult mice as well as in the prospective cohort of children. Importantly, although mouse brains infected later after birth do not have apparent abnormal brain structure, those mice still show significant impairments of visual cortical functions, circuit organization, and experience-dependent plasticity. Thus, the study suggests that special attention should be paid to all children born to ZIKV infected mothers for screening of abnormal behaviors and sensory function during childhood., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by Wiley‐VCH GmbH.)

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.

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., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The Zika outbreak in Brazil caused congenital impairments and developmental delays, or Congenital Zika Syndrome (CZS). We sought to ascertain whether a family support programme was needed and, if so, could be adapted from the Getting to Know Cerebral Palsy programme (GTKCP) designed for children with cerebral palsy (CP). We conducted a systematic review of the needs of families of children with CZS or CP in low- and middle-income countries and reviewed the findings of the Social and Economic Impact of Zika study. We undertook a scoping visit to three facilities offering services to children with CZS in Brazil to understand potential utility and adaptability of GTKCP. The literature review showed that caregivers of children with CZS experience challenges in mental health, healthcare access, and quality of life, consistent with the CP literature. The scoping visits demonstrated that most support provided to families was medically orientated and while informal support networks were established, these lacked structure. Caregivers and practitioners expressed an eagerness for more structure community-based family support programmes. A support programme for families of children with CZS in Brazil appeared relevant and needed, and may fill an important gap in the Zika response.

Background: There are limited data on the natural history of antenatal Zika virus (ZIKV) exposure in twin pregnancies, especially regarding intertwin concordance of prenatal, placental, and infant outcomes., Methods: This prospective cohort study included twin pregnancies referred to a single institution from September 2015 to June 2016 with maternal ZIKV. Polymerase chain reaction (PCR) testing of maternal, placental, and neonatal samples was performed. Prenatal ultrasounds were completed for each twin, and histomorphologic analysis was performed for each placenta. Abnormal neonatal outcome was defined as abnormal exam and/or abnormal imaging. Two- to three-year follow-up of infants included physical exams, neuroimaging, and Bayley-III developmental assessment., Results: Among 244 pregnancies, 4 twin gestations without coinfection were identified. Zika virus infection occurred at 16-33 weeks gestation. Zika virus PCR testing revealed discordance between dichorionic twins, between placentas in a dichorionic pair, between portions of a monochorionic placenta, and between a neonate and its associated placenta. Of the 8 infants, 3 (38%) had an abnormal neonatal outcome. Of 6 infants with long-term follow-up, 3 (50%) have demonstrated ZIKV-related abnormalities., Conclusions: Neonatal PCR testing, placental findings, and infant outcomes can be discordant between co-twins with antenatal ZIKV exposure. These findings demonstrate that each twin should be evaluated independently for vertical transmission., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

This study aims to identify through a systematic review the possible effects of pre-gestational excessive body weight on the composition of polyunsaturated fatty acids in human milk. The papers were selected in the following databases: PubMed, Virtual Health Library, EMBASE, Web of Science and SCOPUS. The search strategy employed descriptors: 'Human Milk' AND 'Obesity' OR 'Overweight' OR 'Body Mass Index' AND 'Fatty acid' OR 'Omega3' OR 'Omega6'. According to the established strategy, six manuscripts were selected. Most of the selected studies concluded that mothers with excessive body weight presented a milk with a higher concentration of omega 6. In addition, all selected studies identified an increased Omega-6/Omega-3 ratio in the milk of pre-gestational excessive body weight mothers compared to the eutrophic ones. The milk of pre-gestational excessive body weight women had a higher Omega-6/Omega-3 ratio, which confirms the importance of starting pregnancy with adequate weight, thus minimising the possible influences that excessive body weight can cause infant health.

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., Competing Interests: The authors have declared that no competing interests exist.

Previous work showed that the thymus can be infected by RNA viruses as HIV and HTLV-1. We thus hypothesized that the thymus might also be infected by the Zika virus (ZIKV). Herein we provide compelling evidence that ZIKV targets human thymic epithelial cells (TEC) in vivo and in vitro. ZIKV-infection enhances keratinization of TEC, with a decrease in proliferation and increase in cell death. Moreover, ZIKV modulates a high amount of coding RNAs with upregulation of genes related to cell adhesion and migration, as well as non-coding genes including miRNAs, circRNAs and lncRNAs. Moreover, we observed enhanced attachment of lymphoblastic T-cells to infected TEC, as well as virus transfer to those cells. Lastly, alterations in thymuses from babies congenitally infected were seen, with the presence of viral envelope protein in TEC. Taken together, our data reveals that the thymus, particularly the thymic epithelium, is a target for the ZIKV with changes in the expression of molecules that are relevant for interactions with developing thymocytes.

The Accreditation Council for Graduate Medical Education (ACGME), which regulates residency and fellowship training in the United States, recently revised the minimum standards for all training programs. These standards are codified and published as the Common Program Requirements. Recent specific revisions, particularly removing the requirement ensuring protected time for core faculty, are poised to have a substantial impact on emergency medicine training programs. A group of representatives and relevant stakeholders from national emergency medicine (EM) organizations was convened to assess the potential effects of these changes on core faculty and the training of emergency physicians. We reviewed the literature and results of surveys conducted by EM organizations to examine the role of core faculty protected time. Faculty nonclinical activities contribute greatly to the academic missions of EM training programs. Protected time and reduced clinical hours allow core faculty to engage in education and research, which are two of the three core pillars of academic EM. Loss of core faculty protected time is expected to have detrimental impacts on training programs and on EM generally. We provide consensus recommendations regarding EM core faculty clinical work hour limitations to maintain protected time for educational activities and scholarship and preserve the quality of academic EM., (© 2019 by the Society for Academic Emergency Medicine.)

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.

Background and Aims: Overweight is ever more prevalent in the pediatric population, and this cardiometabolic factor can be associated with inflammatory markers, gut microbiota composition, and short-chain fatty acid (SCFA) concentrations. The aim of this study is to evaluate to what extent the abundance of gut microbiota phyla, SCFA concentrations, and inflammatory markers are associated with elevated body fat percentage (BF%), overweight, and obesity in female adolescents., Methods: An experimental and comparative study was conducted with 96 girls 14 to 19 years old. They were divided into 3 groups: G1-eutrophic (EUT) and adequate BF%; G2-EUT and high BF%; and G3-overweight (OW) or obese (OB) and high BF%. Waist circumference (WC), waist to height ratio (WtHR), and neck circumference (NC) were analyzed as indicators of central visceral adiposity. The BF% was evaluated by DEXA equipment. A food frequency questionnaire was used to evaluate the main types of food consumed in a week. The abundance of the Firmicutes, Bacteroidetes, and Proteobacteria phyla was measured by real-time polymerase chain reaction (RT-qPCR), and the SFCA concentrations (acetic, butyric, and propionic) were determined by high-performance liquid chromatography (HPLC). The inflammatory markers leptin, tumor necrosis factor-alpha, interleukin-6, and high-sensitivity C-reactive protein (hs-CRP) were assessed., Results: Female adolescents in groups G2 and G3 had greater central visceral adiposity and leptin concentration than those in group G1. No association was found between gut microbiota phyla abundance and SFCA concentrations in any of the groups. WC and frequency of consumption of oily and fatty foods were associated with Firmicutes abundance and SFCA concentrations. Girls with high WC also had the greatest leptin ( p < 0.001) and hs-CRP ( p = 0.035) concentrations., Conclusions: Inflammatory markers showed association with increased BMI and high BF% in female adolescents. The abundance of Firmicutes was associated with WC and NC, but not with BMI classification or BF%. Specifically, WC and the consumption of oils and fats showed correlation with SCFA concentrations. Different anthropometric indicators, such as NC and WC, should be incorporated into the clinical evaluation of the nutritional status of individuals in the adolescent population., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2019 Valter Paulo Neves Miranda et al.)

The implications of Zika Virus exposure in pregnancy for early infant growth remains poorly described. The main goal of this study is to compare the growth, body composition, and feeding modality of infants in the first three months of life by prenatal Zika Virus exposure status. We selected an analytical cohort of 115 infants born without microcephaly, comprising 56 infants with qRT-PCR confirmed exposure to ZIKV during gestation and 59 infants born to women with presumptively no evidence of ZIKV in pregnancy. Infants were evaluated at birth, 1 and 3 months of age in terms of anthropometrics, body composition All the results were adjusted by maternal age, maternal BMI and gestational age. We observe no differences between anthropometric measurements at birth. Mothers in exposed group showed higher BMI. At 1 month and 3 months of age there were differences in mid arm circumference, arm muscle circumference and fat free mass. Weight and length was less in the ZIKV exposed in pregnancy infants and statistically different at 3 month of age. The findings of this investigation provide new evidence that ZIKV exposure in pregnancy may be associated with differences in body composition.